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Sample records for 3-hydroxylase inhibitor ro

  1. Pre-clinical studies of Notch signaling inhibitor RO4929097 in inflammatory breast cancer cells.

    PubMed

    Debeb, Bisrat G; Cohen, Evan N; Boley, Kimberly; Freiter, Erik M; Li, Li; Robertson, Fredika M; Reuben, James M; Cristofanilli, Massimo; Buchholz, Thomas A; Woodward, Wendy A

    2012-07-01

    Basal breast cancer, common among patients presenting with inflammatory breast cancer (IBC), has been shown to be resistant to radiation and enriched in cancer stem cells. The Notch pathway plays an important role in self-renewal of breast cancer stem cells and contributes to inflammatory signaling which promotes the breast cancer stem cell phenotype. Herein, we inhibited Notch signaling using a gamma secretase inhibitor, RO4929097, in an in vitro model that enriches for cancer initiating cells (3D clonogenic assay) and conventional 2D clonogenic assay to compare the effect on radiosensitization of the SUM149 and SUM190 IBC cell lines. RO4929097 downregulated the Notch target genes Hes1, Hey1, and HeyL, and showed a significant reduction in anchorage independent growth in SUM190 and SUM149. However, the putative self-renewal assay mammosphere formation efficiency was increased with the drug. To assess radiosensitization of putative cancer stem cells, cells were exposed to increasing doses of radiation with or without 1 μM RO4929097 in their standard (2D) and self-renewal enriching (3D) culture conditions. In the conventional 2D clonogenic assay, RO4929097 significantly sensitized SUM190 cells to ionizing radiation and has a modest radiosensitization effect in SUM149 cells. In the 3D clonogenic assays, however, a radioprotective effect was seen in both SUM149 and SUM190 cells at higher doses. Both cell lines express IL-6 and IL-8 cytokines known to mediate the efficacy of Notch inhibition and to promote self-renewal of stem cells. We further showed that RO429097 inhibits normal T-cell synthesis of some inflammatory cytokines, including TNF-α, a potential mediator of IL-6 and IL-8 production in the microenvironment. These data suggest that additional targeting agents may be required to selectively target IBC stem cells through Notch inhibition, and that evaluation of microenvironmental influences may shed further light on the potential effects of this inhibitor.

  2. A Phase II Study of RO4929097 Gamma-Secretase Inhibitor in Metastatic Melanoma: SWOG 0933

    PubMed Central

    Lee, Sylvia M.; Moon, James; Redman, Bruce G.; Chidiac, Tarek; Flaherty, Lawrence E.; Zha, Yuanyuan; Othus, Megan; Ribas, Antoni; Sondak, Vernon K.

    2014-01-01

    Background Aberrant Notch activation confers a proliferative advantage onto many human tumors, including melanoma. This phase II trial assessed the antitumor activity of RO4929097, a gamma-secretase inhibitor of Notch signaling, on the progression-free and overall survival of patients with advanced melanoma. Methods Chemotherapy-naïve patients with metastatic melanoma of cutaneous or unknown origin were treated with RO4929097 at a dose of 20 mg orally daily, 3 consecutive days per week. A two-step accrual design was used, with an interim analysis on the first 32 patients, and continuation of enrollment if ≥4/32 patients responded. Results Thirty-six patients from 23 institutions were enrolled; 32 patients were evaluable. RO4929097 was well-tolerated, and most toxicities were grade 1 or 2. The most common toxicities were nausea (53%), fatigue (41%), and anemia (22%). There was 1 confirmed partial response lasting 7 months, and 8 patients with stable disease lasting at least through week 12, with one of these continuing for 31 months. The 6-month PFS was 9% (95% CI: 2–22%), and 1-year OS was 50% (95% CI: 32–66%). Peripheral blood T cell assays showed no significant inhibition of IL-2 production, a surrogate pharmacodynamic marker of Notch inhibition, suggesting that the drug levels were insufficient to achieve Notch target inhibition. Conclusions RO4929097 showed minimal clinical activity against metastatic melanoma in this phase II trial, possibly due to inadequate exposure to therapeutic drug levels. While Notch inhibition remains a compelling target in melanoma, our results do not support further investigation of RO4929097 at this dose and schedule. PMID:25250858

  3. Cholesterol biosynthesis inhibitor RO 48-8071 suppresses growth of hormone-dependent and castration-resistant prostate cancer cells

    PubMed Central

    Liang, Yayun; Mafuvadze, Benford; Aebi, Johannes D; Hyder, Salman M

    2016-01-01

    Standard treatment for primary prostate cancer includes systemic exposure to chemotherapeutic drugs that target androgen receptor or antihormone therapy (chemical castration); however, drug-resistant cancer cells generally emerge during treatment, limiting the continued use of systemic chemotherapy. Patients are then treated with more toxic standard therapies. Therefore, there is an urgent need for novel and more effective treatments for prostate cancer. The cholesterol biosynthetic pathway is an attractive therapeutic target for treating endocrine-dependent cancers because cholesterol is an essential structural and functional component of cell membranes as well as the metabolic precursor of endogenous steroid hormones. In this study, we have examined the effects of RO 48-8071 (4′-[6-(allylmethylamino)hexyloxy]-4-bromo-2′-fluorobenzophenone fumarate; Roche Pharmaceuticals internal reference: RO0488071) (RO), which is an inhibitor of 2, 3-oxidosqualene cyclase (a key enzyme in the cholesterol biosynthetic pathway), on prostate cancer cells. Exposure of both hormone-dependent and castration-resistant human prostate cancer cells to RO reduced prostate cancer cell viability and induced apoptosis in vitro. RO treatment reduced androgen receptor protein expression in hormone-dependent prostate cancer cells and increased estrogen receptor β (ERβ) protein expression in both hormone-dependent and castration-resistant prostate cancer cell lines. Combining RO with an ERβ agonist increased its ability to reduce castration-resistant prostate cancer cell viability. In addition, RO effectively suppressed the growth of aggressive castration-resistant human prostate cancer cell xenografts in vivo without any signs of toxicity to experimental animals. Importantly, RO did not reduce the viability of normal prostate cells in vitro. Our study is the first to demonstrate that the cholesterol biosynthesis inhibitor RO effectively suppresses growth of human prostate cancer cells

  4. Pre-Clinical studies of Notch Signaling Inhibitor RO4929097 in Inflammatory Breast Cancer Cells

    PubMed Central

    Debeb, Bisrat G.; Cohen, Evan N.; Boley, Kimberly; Freiter, Erik M.; Li, Li; Robertson, Fredika M.; Reuben, James M.; Cristofanilli, Massimo; Buchholz, Thomas A.; Woodward, Wendy A.

    2015-01-01

    Basal breast cancer, common among patients presenting with inflammatory breast cancer, has been shown to be resistant to radiation and enriched in cancer stem cells. The Notch pathway plays an important role in self-renewal of breast cancer stem cells and contributes to inflammatory signaling that promotes the breast cancer stem cell phenotype. Herein we inhibited Notch signaling using a gamma secretase inhibitor, RO4929097, in an in vitro model that enriches for cancer initiating cells (3D clonogenic assay) and conventional 2D clonogenic assay to compare the effect on radiosensitization of the SUM149 and SUM190 inflammatory breast cancer (IBC) cell lines. RO4929097 downregulated the Notch target genes Hes1, Hey1 and HeyL and showed a significant reduction in anchorage independent growth in SUM190 and SUM149. However, the putative self-renewal assay mammosphere formation efficiency was increased with the drug. To assess radiosensitization of putative cancer stem cells, cells were exposed to increasing doses of radiation with or without 1uM RO4929097 in their standard (2D) and self-renewal enriching (3D) culture conditions. In the conventional 2D clonogenic assay, RO4929097 significantly sensitized SUM190 cells to ionizing radiation and has a modest radiosensitization effect in SUM149 cells. In the 3D clonogenic assays, however, a radioprotective effect was seen in both SUM149 and SUM190 cells at higher doses. Both cell lines express IL-6 and IL-8, cytokines known to mediate the efficacy of notch inhibition and to promote self-renewal of stem cells. We further showed that RO429097 inhibits normal T-cell synthesis of some inflammatory cytokines, including TNF-α, a potential mediator of IL-6 and IL-8 production in the microenvironment. These data suggest additional targeting agents may be required to selectively target IBC stem cells through notch inhibition, and that evaluation of microenvironmental influences may shed further light on the potential effects of this

  5. Ro 32-3555, an orally active collagenase inhibitor, prevents cartilage breakdown in vitro and in vivo.

    PubMed

    Lewis, E J; Bishop, J; Bottomley, K M; Bradshaw, D; Brewster, M; Broadhurst, M J; Brown, P A; Budd, J M; Elliott, L; Greenham, A K; Johnson, W H; Nixon, J S; Rose, F; Sutton, B; Wilson, K

    1997-06-01

    1. Ro 32-3555 (3(R)-(cyclopentylmethyl)-2(R)-[(3,4,4-trimethyl-2,5-dioxo-1- imidazolidinyl)methyl]-4-oxo-4-piperidinobutyrohydroxamic acid) is a potent, competitive inhibitor of human collagenases 1, 2 and 3 (Ki values of 3.0, 4.4 and 3.4 nM, respectively). The compound is a selective inhibitor of collagenases over the related human matrix metalloproteinases stromelysin 1, and gelatinases A and B (Ki values of 527, 154 and 59 nM, respectively). 2. Ro 32-3555 inhibited interleukin-1 alpha (IL-1 alpha)-induced cartilage collagen degradation in vitro in bovine nasal cartilage explants (IC50 = 60 nM). 3. Ro 32-3555 was well absorbed in rats when administered orally. Systemic exposure was dose related, with an oral bioavailability of 26% at a dose of 25 mg kg-1. 4. Ro 32-3555 prevented granuloma-induced degradation of bovine nasal cartilage cylinders implanted subcutaneously into rats (ED50 = 10 mg kg-1, twice daily, p.o.). 5. Ro 32-3555 dosed once daily for 14 days at 50 mg kg-1, p.o., inhibited degradation of articular cartilage in a rat monoarthritis model induced by an intra-articular injection of Propionibacterium acnes. 6. Ro 32-3555 is a potential therapy for the treatment of the chronic destruction of articulating cartilage in both rheumatoid and osteoarthritis.

  6. The PA endonuclease inhibitor RO-7 protects mice from lethal challenge with influenza A or B viruses.

    PubMed

    Jones, Jeremy C; Marathe, Bindumadhav M; Vogel, Peter; Gasser, Rodolfo; Najera, Isabel; Govorkova, Elena A

    2017-02-13

    Current influenza treatment relies on a single class of antiviral drugs, the neuraminidase inhibitors (NAIs), raising concern over the potential emergence of resistant variants and necessitating the development of novel drugs. In recent years, investigational inhibitors targeting the endonuclease activity of the influenza acidic polymerase (PA) protein have yielded encouraging results, although there are only limited data on their in vivo efficacy. Here, we examined the antiviral potential of the PA endonuclease inhibitor RO-7 in prophylactic and therapeutic regimens in BALB/c mice inoculated with influenza A/California/04/2009 (H1N1)pdm09 or B/Brisbane/60/2008 viruses, which represent currently circulating antigenic variants. RO-7 was administered to mice intraperitoneally twice daily at dosages of 6, 15, or 30 mg/kg/day for 5 days, starting 4 h before or 24 or 48 h after virus inoculation, and showed no adverse effects. Prophylactic administration completely protected mice from lethal infection by influenza A or B virus. The level of therapeutic protection conferred depended upon the time of treatment initiation and RO-7 dosage, resulting in 60%-100% and 80%-100% survival with influenza A and B viruses, respectively. RO-7 treatment significantly decreased virus titers in the lung and lessened the extent and severity of lung damage. No PA endonuclease-inhibitor resistance was observed in viruses isolated from lungs of RO-7-treated mice, and the viruses remained susceptible to the drug at nanomolar concentrations in phenotypic assays. These in vivo efficacy results further highlight the potential of RO-7 for development as antiviral therapy for influenza A and B virus infections.

  7. Jumping the nuclear envelop barrier: Improving polyplex-mediated gene transfection efficiency by a selective CDK1 inhibitor RO-3306.

    PubMed

    Zhou, Xuefei; Liu, Xiangrui; Zhao, Bingxiang; Liu, Xin; Zhu, Dingcheng; Qiu, Nasha; Zhou, Quan; Piao, Ying; Zhou, Zhuxian; Tang, Jianbin; Shen, Youqing

    2016-07-28

    Successful transfection of plasmid DNA (pDNA) requires intranuclear internalization of pDNA effectively and the nuclear envelope appears to be one of the critical intracellular barriers for polymer mediated pDNA delivery. Polyethylenimine (PEI), as the classic cationic polymer, compact the negatively charged pDNA tightly and make up stable polyplexes. The polyplexes are too large to enter the nuclear through nuclear pores and it is believed that the nuclear envelope breakdown in mitosis could facilitate the nuclear entry of polyplexes. To jump the nuclear envelope barrier, we used a selective and reversible CDK1 inhibitor RO-3306 to control the G2/M transition of the cell cycle and increased the proportion of mitotic cells which have disappeared nuclear envelope during transfection. Herein, we show that RO-3306 remarkably increases the transfection efficiency of PEI polyplexes through enhanced nuclear localization of PEI and pDNA. However, RO-3306 is less effective to the charge-reversal polymer poly[(2-acryloyl)ethyl(p-boronic acid benzyl)diethylammonium bromide] (B-PDEAEA) which responses to cellular stimuli and releases free pDNA in cytoplasm. Our findings not only offer new opportunities for improving non-viral based gene delivery but also provide theoretical support for the rational design of novel functional polymers for gene delivery. We also report current data showing that RO-3306 synergizes TRAIL gene induced apoptosis in cancer cells.

  8. Effects of the selective protein kinase C inhibitor, Ro 31-7549, on the proliferation of cultured mouse epidermal keratinocytes.

    PubMed

    Bollag, W B; Ducote, J; Harmon, C S

    1993-03-01

    We have investigated the effects of Ro 31-7549, a selective protein kinase C (PKC) inhibitor, on DNA synthesis and proliferation in two primary mouse epidermal keratinocyte culture systems. In differentiating keratinocytes incubated in medium containing 10% serum and high calcium (approximately 0.5 mM), Ro 31-7549 blocked the inhibitory effect of the phorbol ester 12-0-tetradecanoyl-13-acetate (TPA) (a PKC activator) on keratinocyte DNA synthesis at 24 h [50% maximal response concentration (EC50) = 1 microM], consistent with inhibition of PKC-mediated differentiation. Continuous treatment of the differentiative culture system with the PKC inhibitor resulted in a marked (fourfold) stimulation of [3H]thymidine incorporation at day 7 of exposure, with an EC50 of 0.25 microM. The potencies of these effects of Ro 31-7549 are comparable to that reported for inhibition of TPA-induced platelet 47-kD protein phosphorylation [50% inhibitory concentration (IC50) = 4.4 microM]. The time course of [3H]thymidine incorporation indicated that Ro 31-7549 did not directly stimulate DNA synthesis but instead prevented the loss of proliferative capacity associated with continued culture in this medium. Maximal stimulation (2.6 times) of DNA synthesis was observed on day 4, whereas DNA synthesis at day 1 was unaffected. In a highly proliferative culture system using serum-free medium containing 25 microM calcium, TPA dose-dependently inhibited proliferation with an IC50 of approximately 0.3 mM. This antiproliferative effect of TPA was largely reversed by 0.1 microM Ro 31-7549. In the proliferative culture system, 0.75 microM Ro 31-7549 also essentially reversed the inhibition of proliferation caused by switching to high (1.0 mM) calcium. These results suggest that the loss of proliferative capacity in differentiating epidermal keratinocyte cultures may be mediated, at least in part, by PKC.

  9. Activation of HIV-1 from latent infection via synergy of RUNX1 inhibitor Ro5-3335 and SAHA.

    PubMed

    Klase, Zachary; Yedavalli, Venkat S R K; Houzet, Laurent; Perkins, Molly; Maldarelli, Frank; Brenchley, Jason; Strebel, Klaus; Liu, Paul; Jeang, Kuan-Teh

    2014-03-01

    A major barrier to the elimination of HIV-1 infection is the presence of a pool of long-lived, latently infected CD4+ memory T-cells. The search for treatments to re-activate latent HIV to aid in clearance is hindered by the incomplete understanding of the mechanisms that lead to transcriptional silencing of viral gene expression in host cells. Here we identify a previously unknown role for RUNX1 in HIV-1 transcriptional latency. The RUNX proteins, in combination with the co-factor CBF-β, are critical transcriptional regulators in T-cells. RUNX1 strongly modulates CD4 expression and contributes to CD4+ T-cell function. We show that RUNX1 can bind DNA sequences within the HIV-1 LTR and that this binding represses transcription. Using patient samples we show a negative correlation between RUNX1 expression and viral load. Furthermore, we find that pharmacologic inhibition of RUNX1 by a small molecule inhibitor, Ro5-3335, synergizes with the histone deacetylase (HDAC) inhibitor SAHA (Vorinostat) to enhance the activation of latent HIV-1 in both cell lines and PBMCs from patients. Our findings indicate that RUNX1 and CBF-β cooperate in cells to modulate HIV-1 replication, identifying for the first time RUNX1 as a cellular factor involved in HIV-1 latency. This work highlights the therapeutic potential of inhibitors of RUNX1 to re-activate virus and aid in clearance of HIV-1.

  10. Synthesis of ({sup 11}C) RO 19 6327, a highly selective and reversible monoamine oxidase B inhibitor potentially useful for treatment of Parkinson`s disease

    SciTech Connect

    Ding, Y.S.; Rehder, K.; Vassello, M.

    1994-05-01

    The potential neuroprotective effect of monoamine oxidase B (MAO B) inhibitors has stimulated intense interest in characterizing their modes of action and in developing new MAO B inhibitor drugs with different properties for clinical investigation in Parkinson`s disease and other enurodegenerative diseases. One of these drugs is Ro 19 6327 (N-(2-aminoethyl)-5-chloro-2-pyridine carboxamide {center_dot}HCl). Ro 19 6327 differs from the suicide inhibitor L-deprenyl in that it is more specific, greater than twenty times as potent in inhibiting MAO B, has no amphetamine metabolites, and is reversible. The recovery of MAO B activity 36 hours after Ro19 6327 treatment discontinuation is relevant in clinical studies since treatment can be withdrawn and changed without the complication of long term effects, as is seen with L-deprenyl. We report here a new synthetic approach to the precursor for Ro 19 6327 suitable for subsequent C-11 labeling for PET studies. Homolytic amidation of 3-chloropyridine afforded 5-chlor-2-pyridinecarboxamide which upon treatment with formaldehyde yielded 5-chlor-N-(hydroxymethyl)-2-pyridinecarboxamide. Conversion to the corresponding acetate afforded a substrate for the displacement reaction with ({sup 11}C) cyanide. Finding a highly selective reducing reagent for the following reduction step was crucial due t;o the presence of four reducible functional groups within the molecule, namely chlorine, pyridine ring, amide, and nitrile. Sodium borohydride in the presence of aluminum chloride was by far the most effective reagent. The final product was then purified by HPLC. The pharmacokinetics, regional distribution and metabolism of ({sup 11}C)Ro 19 6317 are currently under investigation with PET.

  11. Molecular Targeting of the Oncoprotein PLK1 in Pediatric Acute Myeloid Leukemia: RO3280, a Novel PLK1 Inhibitor, Induces Apoptosis in Leukemia Cells

    PubMed Central

    Wang, Na-Na; Li, Zhi-Heng; Zhao, He; Tao, Yan-Fang; Xu, Li-Xiao; Lu, Jun; Cao, Lan; Du, Xiao-Juan; Sun, Li-Chao; Zhao, Wen-Li; Xiao, Pei-Fang; Fang, Fang; Su, Guang-Hao; Li, Yan-Hong; Li, Gang; Li, Yi-Ping; Xu, Yun-Yun; Zhou, Hui-Ting; Wu, Yi; Jin, Mei-Fang; Liu, Lin; Ni, Jian; Wang, Jian; Hu, Shao-Yan; Zhu, Xue-Ming; Feng, Xing; Pan, Jian

    2015-01-01

    Polo-like kinase 1 (PLK1) is highly expressed in many cancers and therefore a biomarker of transformation and potential target for the development of cancer-specific small molecule drugs. RO3280 was recently identified as a novel PLK1 inhibitor; however its therapeutic effects in leukemia treatment are still unknown. We found that the PLK1 protein was highly expressed in leukemia cell lines as well as 73.3% (11/15) of pediatric acute myeloid leukemia (AML) samples. PLK1 mRNA expression was significantly higher in AML samples compared with control samples (82.95 ± 110.28 vs. 6.36 ± 6.35; p < 0.001). Kaplan-Meier survival analysis revealed that shorter survival time correlated with high tumor PLK1 expression (p = 0.002). The 50% inhibitory concentration (IC50) of RO3280 for acute leukemia cells was between 74 and 797 nM. The IC50 of RO3280 in primary acute lymphocytic leukemia (ALL) and AML cells was between 35.49 and 110.76 nM and 52.80 and 147.50 nM, respectively. RO3280 induced apoptosis and cell cycle disorder in leukemia cells. RO3280 treatment regulated several apoptosis-associated genes. The regulation of DCC, CDKN1A, BTK, and SOCS2 was verified by western blot. These results provide insights into the potential use of RO3280 for AML therapy; however, the underlying mechanisms remain to be determined. PMID:25574601

  12. Identification of phenylalanine 3-hydroxylase for meta-tyrosine biosynthesis.

    PubMed

    Zhang, Wenjun; Ames, Brian D; Walsh, Christopher T

    2011-06-21

    Phenylalanine hydroxylase (PheH) is an iron(II)-dependent enzyme that catalyzes the hydroxylation of aromatic amino acid l-phenylalanine (L-Phe) to l-tyrosine (L-Tyr). The enzymatic modification has been demonstrated to be highly regiospecific, forming proteinogenic para-Tyr (p-Tyr) exclusively. Here we biochemically characterized the first example of a phenylalanine 3-hydroxylase (Phe3H) that catalyzes the synthesis of meta-Tyr (m-Tyr) from Phe. Subsequent mutagenesis studies revealed that two residues in the active site of Phe3H (Cys187 and Thr202) contribute to C-3 rather than C-4 hydroxylation of the phenyl ring. This work sets the stage for the mechanistic and structural study of regiospecific control of the substrate hydroxylation by PheH.

  13. Bone matrix hypermineralization in prolyl-3 hydroxylase 1 deficient mice.

    PubMed

    Fratzl-Zelman, Nadja; Bächinger, Hans-Peter; Vranka, Janice A; Roschger, Paul; Klaushofer, Klaus; Rauch, Frank

    2016-04-01

    Lack of prolyl 3-hydroxylase 1 (P3H1) due to mutations in P3H1 results in severe forms of recessive osteogenesis imperfecta. In the present study, we investigated the bone tissue characteristics of P3H1 null mice. Histomorphometric analyses of cancellous bone in the proximal tibia and lumbar vertebra in 1-month and 3-month old mice demonstrated that P3H1 deficient mice had low trabecular bone volume and low mineral apposition rate, but normal osteoid maturation time and normal osteoblast and osteoclast surfaces. Quantitative backscattered electron imaging revealed that the bone mineralization density distribution was shifted towards higher values, indicating hypermineralization of bone matrix. It thus appears that P3H1 deficiency leads to decreased deposition of extracellular matrix by osteoblasts and increased incorporation of mineral into the matrix.

  14. Synthesis of [{sup 18}F]Ro41-0960, a potent COMT inhibitor, for use in vivo mapping with PET

    SciTech Connect

    Ding, Y.S.; Sugano, Y.; Gatley, S.J.

    1995-05-01

    Catechol-O-methyltransferase (COMPT; EC 2.1.1.6) is one of the two major enzymes which metabolize the catecholamine neurotransmitters. It is distributed throughout the body and brain and is elevated in breast cancer tissue when it plays a role in estrogen metabolism. It is also an important molecular target in the development of drugs to treat Parkinson`s disease (PD). Because COMT regulates the concentration of important neurotransmitter amines such as dopamine, there is speculation that abnormalities in its activity may be associated with neurological, and psychiatric disorders. Ro41-9060(3,4-dihydroxy-5-nitro-2{prime}-fluorobenzophenone) is a potent, fluorine containing COMT inhibitor which has been reported to cross the blood brain barrier. It is structurally similar to Ro40-7592 which is currently undergoing clinical trials in PD. We report the synthesis of [{sup 18}F]Ro41-0960, for investigation for mapping COMT and for studies of COMT drugs. [{sup 18}F]Ro41-0960 was synthesized by the nucleophilic aromatic substitution reaction with NCA [{sup 18}F] fluoride on a protected precursor (prepared via a five-step synthesis) followed by hydrolysis with HBr (synthesis time of 100 min; radiochemical yield of 5-7% (EOB)). Though Ro41-0960 has been reported to cross the blood brain barrier, PET studies in baboon demonstrated that an almost complete absence of the drug from the brain both at tracer doses and with the addition of unlabeled drug (1.5 mg/kg) at all times through a 90 min experimental interval. The plasma to brain ratios of F-18 average about 40:1. However, high uptake was observed in the kidneys and in other organs which are known to have high COMT. Studies in mice showed that at 30 min after injection of tracer, F-18 in kidneys was largely as [{sup 18}F]Ro-41-0960 and that it could be displaced with unlabeled Ro41-0960. These studies provide the first example of a positron emitter labeled COMT radiotracer.

  15. The selective protein kinase C inhibitor, Ro-31-8220, inhibits mitogen-activated protein kinase phosphatase-1 (MKP-1) expression, induces c-Jun expression, and activates Jun N-terminal kinase.

    PubMed

    Beltman, J; McCormick, F; Cook, S J

    1996-10-25

    The role of protein kinase C (PKC) in inflammation, mitogenesis, and differentiation has been deduced in part through the use of a variety of PKC inhibitors. Two widely used inhibitors are the structurally related compounds GF109203X and Ro-31-8220, both of which potently inhibit PKC activity and are believed to be highly selective. While using GF109203X and Ro-31-8220 to address the role of PKC in immediate early gene expression, we observed striking differential effects by each of these two compounds. Growth factors induce the expression of the immediate early gene products MAP kinase phosphatase-1 (MKP-1), c-Fos and c-Jun. Ro-31-8220 inhibits growth factor-stimulated expression of MKP-1 and c-Fos but strongly stimulated c-Jun expression, even in the absence of growth factors. GF109203X displays none of these properties. These data suggest that Ro-31-8220 may have other pharmacological actions in addition to PKC inhibition. Indeed, Ro-31-8220 strongly stimulates the stress-activated protein kinase, JNK1. Furthermore, Ro-31-8220 apparently activates JNK in a PKC-independent manner. Neither the down-regulation of PKC by phorbol esters nor the inhibition of PKC by GF109203X affected the ability of Ro-31-8220 to activate JNK1. These data suggest that, in addition to potently inhibiting PKC, Ro-31-8220 exhibits novel pharmacological properties which are independent of its ability to inhibit PKC.

  16. Silencing of flavanone-3-hydroxylase in apple (Malus × domestica Borkh.) leads to accumulation of flavanones, but not to reduced fire blight susceptibility.

    PubMed

    Flachowsky, Henryk; Halbwirth, Heidi; Treutter, Dieter; Richter, Klaus; Hanke, Magda-Viola; Szankowski, Iris; Gosch, Christian; Stich, Karl; Fischer, Thilo C

    2012-02-01

    Transgenic antisense flavanone-3-hydroxylase apple plants were produced to mimic the effect of the agrochemical prohexadione-Ca on apple leaves. This enzyme inhibitor for 2-oxoglutarate dependent dioxygenases is used as a growth retardant and for control of secondary fire blight of leaves. Like using the agent, silencing of flavanone-3-hydroxylase leads to an accumulation of flavanones in leaves, but in contrast not to the formation of 3-deoxyflavonoids. In prohexadione-Ca treated leaves the 3-deoxyflavonoid luteoforol is formed from accumulating flavanones, acting as an antimicrobial compound against the fire blight pathogen Erwinia amylovora. Seemingly, the silencing of just one of the 2-oxoglutarate dependent dioxygenases (in apple also flavonol synthase and anthocyanidin synthase take part downstream in the pathway) does not provide a sufficiently high ratio of flavanones to dihydroflavonols. This seems to be needed to let the dihydroflavonol-4-reductase/flavanone-4-reductase enzyme reduce flavanones to luteoforol, and to let this be reduced by the leucoanthocyanidin-4-reductase/3-deoxyleucoanthocyanidin-4-reductase, each acting with their respective weak secondary activities. Accordingly, also the intended inducible resistance to fire blight by prohexadione-Ca is not observed with the antisense flavanone-3-hydroxylase apple plants. On the other hand, for most transgenic lines with strong flavanone-4-reductase down-regulation, up-regulation of gene expression for the other flavonoid genes was found. This provides further evidence for the feedback regulation of flavonoid gene expression having been previously reported for the prohexadione-Ca inhibited apple plants.

  17. PLGA-PEG Nanoparticles Coated with Anti-CD45RO and Loaded with HDAC Plus Protease Inhibitors Activate Latent HIV and Inhibit Viral Spread

    NASA Astrophysics Data System (ADS)

    Tang, Xiaolong; Liang, Yong; Liu, Xinkuang; Zhou, Shuping; Liu, Liang; Zhang, Fujina; Xie, Chunmei; Cai, Shuyu; Wei, Jia; Zhu, Yongqiang; Hou, Wei

    2015-10-01

    Activating HIV-1 proviruses in latent reservoirs combined with inhibiting viral spread might be an effective anti-HIV therapeutic strategy. Active specific delivery of therapeutic drugs into cells harboring latent HIV, without the use of viral vectors, is a critical challenge to this objective. In this study, nanoparticles of poly(lactic-co-glycolic acid)-polyethylene glycol diblock copolymers conjugated with anti-CD45RO antibody and loaded with the histone deacetylase inhibitor suberoylanilide hydroxamic acid (SAHA) and/or protease inhibitor nelfinavir (Nel) were tested for activity against latent virus in vitro. Nanoparticles loaded with SAHA, Nel, and SAHA + Nel were characterized in terms of size, surface morphology, zeta potential, entrapment efficiency, drug release, and toxicity to ACH-2 cells. We show that SAHA- and SAHA + Nel-loaded nanoparticles can target latently infected CD4+ T-cells and stimulate virus production. Moreover, nanoparticles loaded with SAHA + NEL were capable of both activating latent virus and inhibiting viral spread. Taken together, these data demonstrate the potential of this novel reagent for targeting and eliminating latent HIV reservoirs.

  18. Genes encoding p-coumarate 3-hydroxylase (C3H) and methods of use

    DOEpatents

    Chapple, Clinton C. S.; Franke, Rochus; Ruegger, Max O.

    2006-07-04

    The present invention is directed to a method for altering secondary metabolism in plants, specifically phenylpropanoid metabolism. The present invention is further directed to a mutant p-coumarate 3-hydroxylase gene, referred to herein as the ref8 gene, its protein product which can be used to prepare gene constructs and transgenic plants. The gene constructs and transgenic plants are further aspects of the present invention.

  19. Validation and implementation of a liquid chromatography/tandem mass spectrometry assay for quantitation of the total and unbound RO4929097, a γ-secretase inhibitor targeting Notch signaling, in human plasma

    PubMed Central

    Wu, Jianmei; Wiegand, Richard; LoRusso, Patricia; Li, Jing

    2013-01-01

    A reversed-phased liquid chromatography with tandem mass spectrometry (LC-MS/MS) method was developed and validated for quantitation of the total and unbound RO4929097, a γ-secretase inhibitor targeting Notch signaling, in human plasma. Sample preparation involved a liquid-liquid extraction with ethyl acetate. Chromatographic separation was achieved on a Waters X-Terra™ MS C18 column with an isocratic mobile phase consisting of methanol/0.45% formic acid in water (60:40,v/v) running at a flow rate of 0.2 ml/min for 6min. The lower limits of quantitation (LLOQs) were 5 ng/ml for the total RO4929097 in plasma and 0.5 ng/ml for the unbound drug in phosphate buffer solution (PBS). Calibration curves were linear over RO4929097 concentration range of 5–2000 ng/ml in plasma for the total drug and 0.5–200 ng/ml in PBS for the unbound drug. The intra-day and inter-day accuracy and precision were within the generally accepted criteria for bioanalytical method (< 15%). The method has been successfully employed to characterize the total and unbound plasma pharmacokinetics of RO4929097 after its oral administration in cancer patients. PMID:21497565

  20. (E)-2(R)-[1(S)-(Hydroxycarbamoyl)-4-phenyl-3-butenyl]-2'-isobutyl-2'-(methanesulfonyl)-4-methylvalerohydrazide (Ro 32-7315), a selective and orally active inhibitor of tumor necrosis factor-alpha convertase.

    PubMed

    Beck, G; Bottomley, G; Bradshaw, D; Brewster, M; Broadhurst, M; Devos, R; Hill, C; Johnson, W; Kim, H-J; Kirtland, S; Kneer, J; Lad, N; Mackenzie, R; Martin, R; Nixon, J; Price, G; Rodwell, A; Rose, F; Tang, J-P; Walter, D S; Wilson, K; Worth, E

    2002-07-01

    Tumor necrosis factor-alpha (TNF-alpha), a cytokine secreted by inflammatory cells, has been implicated in several inflammatory disease states. (E)-2(R)-[1(S)-(Hydroxycarbamoyl)-4-phenyl-3-butenyl]-2'-isobutyl-2'-(methanesulfonyl)-4-methylvalerohydrazide (Ro 32-7315), is a potent, orally active inhibitor of the TNF-alpha convertase (TACE), an enzyme responsible for proteolytic cleavage of the membrane bound precursor, pro-TNF-alpha. Ro 32-7315 inhibited a recombinant form of TACE (IC(50) = 5.2 nM) with selectivity over related matrix metalloproteinases. In a cellular assay system, THP-1 cell line, and in human and rat whole blood, Ro 32-7315 significantly reduced lipopolysaccharide (LPS)-induced TNF-alpha release with IC(50) values of 350 +/- 14 nM (n = 5), 2.4 +/- 0.5 microM (n = 5), and 110 +/- 18 nM (n = 5), respectively. Oral administration of Ro 32-7315 to Wistar rats caused a dose-dependent inhibition of LPS-induced release of systemic TNF-alpha with an ED(50) of 25 mg/kg. Treatment (days 0-14) of Allen and Hamburys hooded rats with Ro 32-7315 (2.5, 5, 10, and 20 mg/kg, i.p., twice daily) significantly reduced adjuvant-induced secondary paw swelling (42, 71, 83, and 93%, respectively) as compared with the vehicle group. In the Ro 32-7315-treated group, the reduced paw swelling was associated with improved lesion score and joint mobility. Furthermore, in a placebo-controlled, single-dose study, Ro 32-7315 given orally (450 mg) significantly suppressed ex vivo, LPS-induced TNF-alpha release in the whole-blood samples taken from healthy male and female volunteers (mean inhibition of 42% over a 4-h duration, n = 6). These data collectively support the potential use of such a compound for the oral treatment of inflammatory disorders.

  1. Cloning, functional expression, and characterization of a chalcone 3-hydroxylase from Cosmos sulphureus.

    PubMed

    Schlangen, Karin; Miosic, Silvija; Thill, Jana; Halbwirth, Heidi

    2010-07-01

    A chalcone 3-hydroxylase (CH3H) cDNA clone was isolated and characterized from Cosmos sulphureus petals accumulating butein (2',3,4,4'-tetrahydroxychalcone) derivatives as yellow flower pigments. The recombinant protein catalyses the introduction of an additional hydroxyl group in the B-ring of chalcones, a reaction with high similarity to the hydroxylation of flavonoids catalysed by the well-studied flavonoid 3'-hydroxylase (F3'H). CH3H shows high specificity for chalcones, but a low F3'H activity was also detected. By contrast, the common F3'H from C. sulphureus does not accept chalcones as substrates and is therefore unlikely to be involved in the creation of the B-ring hydroxylation pattern of the yellow flower pigments. CH3H was primarily expressed in young buds, the main tissue for chalcone pigment formation. Expression levels in open flowers and 3-d-old seedlings were lower and almost no CH3H expression was observed in leaves. F3'H, in contrast, showed the highest expression also in buds, but comparable expression rates in all other tissues tested. Recombinant hybrid proteins constructed from CH3H and F3'H fragments demonstrated that amino acid residues at a substrate recognition site and an insertion of four amino acid residues in a putative loop region have an impact on chalcone acceptance. This is the first identification of a CH3H cDNA from any plant species.

  2. Characterization of antralin: an endogenous protein inhibitor of radioligand binding to (/sup 3/H)RO 5-4864 and (/sup 3/H)nitrendipine binding sites

    SciTech Connect

    Mantione, C.R.; Goldman, M.E.; Bolger, G.T.; Lueddens, H.W.M.; Paul, S.M.; Skolnick, P.

    1986-03-01

    The presence of substances isolated from rat antral stomach that inhibit the binding of (/sup 3/H)Ro 5-4864 (4'-chlorodiazepam) to peripheral-type benzodiazepine receptors (PBR), but do not affect the binding of (/sup 3/H)diazepam to brain-type benzodiazepine receptors have been described. These substances, now obtained by isolation on Sep-Pak C/sub 18/ cartridges, also had no effect on (/sup 3/)PK 11195 binding which labels an antagonist site associated with PBR. Neither was any significant inhibition of (/sup 3/H)Ro 15-1788, (/sup 3/H)..beta..CCM, or (/sup 3/H)dihydroalprenolol binding observed. However, the Sep-Pak eluates were found to produce a concentration-dependent inhibition of (/sup 3/H)nitrendipine binding equivalent to that seen with (/sup 3/H)Ro 5-4864. This material, termed antralin, reduced the apparent K/sub d/ of both radioligands without significantly affecting B/sub max/. Its activity was destroyed by both heat treatment and pronase, and partially reduced by trypsin. Furthermore, its activity was enhanced by Ca/sup + +/ (0.1 mM). Antralin levels were unevenly distributed in rat tissues. These findings suggest that antralin is a protein that may regulate both PBR and dihydropyridine Ca/sup + +/-channel antagonist binding sites in vivo.

  3. Identification of benzodiazepine Ro5-3335 as an inhibitor of CBF leukemia through quantitative high throughput screen against RUNX1-CBFβ interaction.

    PubMed

    Cunningham, Lea; Finckbeiner, Steven; Hyde, R Katherine; Southall, Noel; Marugan, Juan; Yedavalli, Venkat R K; Dehdashti, Seameen Jean; Reinhold, William C; Alemu, Lemlem; Zhao, Ling; Yeh, Jing-Ruey Joanna; Sood, Raman; Pommier, Yves; Austin, Christopher P; Jeang, Kuan-Teh; Zheng, Wei; Liu, Paul

    2012-09-04

    Core binding factor (CBF) leukemias, those with translocations or inversions that affect transcription factor genes RUNX1 or CBFB, account for ~24% of adult acute myeloid leukemia (AML) and 25% of pediatric acute lymphocytic leukemia (ALL). Current treatments for CBF leukemias are associated with significant morbidity and mortality, with a 5-y survival rate of ~50%. We hypothesize that the interaction between RUNX1 and CBFβ is critical for CBF leukemia and can be targeted for drug development. We developed high-throughput AlphaScreen and time-resolved fluorescence resonance energy transfer (TR-FRET) methods to quantify the RUNX1-CBFβ interaction and screen a library collection of 243,398 compounds. Ro5-3335, a benzodiazepine identified from the screen, was able to interact with RUNX1 and CBFβ directly, repress RUNX1/CBFB-dependent transactivation in reporter assays, and repress runx1-dependent hematopoiesis in zebrafish embryos. Ro5-3335 preferentially killed human CBF leukemia cell lines, rescued preleukemic phenotype in a RUNX1-ETO transgenic zebrafish, and reduced leukemia burden in a mouse CBFB-MYH11 leukemia model. Our data thus confirmed that RUNX1-CBFβ interaction can be targeted for leukemia treatment and we have identified a promising lead compound for this purpose.

  4. Salicylic acid 3-hydroxylase regulates Arabidopsis leaf longevity by mediating salicylic acid catabolism

    PubMed Central

    Zhang, Kewei; Halitschke, Rayko; Yin, Changxi; Liu, Chang-Jun; Gan, Su-Sheng

    2013-01-01

    The plant hormone salicylic acid (SA) plays critical roles in plant defense, stress responses, and senescence. Although SA biosynthesis is well understood, the pathways by which SA is catabolized remain elusive. Here we report the identification and characterization of an SA 3-hydroxylase (S3H) involved in SA catabolism during leaf senescence. S3H is associated with senescence and is inducible by SA and is thus a key part of a negative feedback regulation system of SA levels during senescence. The enzyme converts SA (with a Km of 58.29 µM) to both 2,3-dihydroxybenzoic acid (2,3-DHBA) and 2,5-DHBA in vitro but only 2,3-DHBA in vivo. The s3h knockout mutants fail to produce 2,3-DHBA sugar conjugates, accumulate very high levels of SA and its sugar conjugates, and exhibit a precocious senescence phenotype. Conversely, the gain-of-function lines contain high levels of 2,3-DHBA sugar conjugates and extremely low levels of SA and its sugar conjugates and display a significantly extended leaf longevity. This research reveals an elegant SA catabolic mechanism by which plants regulate SA levels by converting it to 2,3-DHBA to prevent SA overaccumulation. The research also provides strong molecular genetic evidence for an important role of SA in regulating the onset and rate of leaf senescence. PMID:23959884

  5. Salicylic acid 3-hydroxylase regulates Arabidopsis leaf longevity by mediating salicylic acid catabolism.

    PubMed

    Zhang, Kewei; Halitschke, Rayko; Yin, Changxi; Liu, Chang-Jun; Gan, Su-Sheng

    2013-09-03

    The plant hormone salicylic acid (SA) plays critical roles in plant defense, stress responses, and senescence. Although SA biosynthesis is well understood, the pathways by which SA is catabolized remain elusive. Here we report the identification and characterization of an SA 3-hydroxylase (S3H) involved in SA catabolism during leaf senescence. S3H is associated with senescence and is inducible by SA and is thus a key part of a negative feedback regulation system of SA levels during senescence. The enzyme converts SA (with a Km of 58.29 µM) to both 2,3-dihydroxybenzoic acid (2,3-DHBA) and 2,5-DHBA in vitro but only 2,3-DHBA in vivo. The s3h knockout mutants fail to produce 2,3-DHBA sugar conjugates, accumulate very high levels of SA and its sugar conjugates, and exhibit a precocious senescence phenotype. Conversely, the gain-of-function lines contain high levels of 2,3-DHBA sugar conjugates and extremely low levels of SA and its sugar conjugates and display a significantly extended leaf longevity. This research reveals an elegant SA catabolic mechanism by which plants regulate SA levels by converting it to 2,3-DHBA to prevent SA overaccumulation. The research also provides strong molecular genetic evidence for an important role of SA in regulating the onset and rate of leaf senescence.

  6. Cell wall modifications triggered by the down-regulation of Coumarate 3-hydroxylase-1 in maize.

    PubMed

    Fornalé, Silvia; Rencoret, Jorge; Garcia-Calvo, Laura; Capellades, Montserrat; Encina, Antonio; Santiago, Rogelio; Rigau, Joan; Gutiérrez, Ana; Del Río, José-Carlos; Caparros-Ruiz, David

    2015-07-01

    Coumarate 3-hydroxylase (C3H) catalyzes a key step of the synthesis of the two main lignin subunits, guaiacyl (G) and syringyl (S) in dicotyledonous species. As no functional data are available in regards to this enzyme in monocotyledonous species, we generated C3H1 knock-down maize plants. The results obtained indicate that C3H1 participates in lignin biosynthesis as its down-regulation redirects the phenylpropanoid flux: as a result, increased amounts of p-hydroxyphenyl (H) units, lignin-associated ferulates and the flavone tricin were detected in transgenic stems cell walls. Altogether, these changes make stem cell walls more degradable in the most C3H1-repressed plants, despite their unaltered polysaccharide content. The increase in H monomers is moderate compared to C3H deficient Arabidopsis and alfalfa plants. This could be due to the existence of a second maize C3H protein (C3H2) that can compensate the reduced levels of C3H1 in these C3H1-RNAi maize plants. The reduced expression of C3H1 alters the macroscopic phenotype of the plants, whose growth is inhibited proportionally to the extent of C3H1 repression. Finally, the down-regulation of C3H1 also increases the synthesis of flavonoids, leading to the accumulation of anthocyanins in transgenic leaves.

  7. Overexpression of a tomato flavanone 3-hydroxylase-like protein gene improves chilling tolerance in tobacco.

    PubMed

    Meng, Chen; Zhang, Song; Deng, Yong-Sheng; Wang, Guo-Dong; Kong, Fan-Ying

    2015-11-01

    Flavonoids are secondary metabolites found in plants with a wide range of biological functions, such as stress protection. This study investigated the functions of a tomato (Solanum lycopersicum) flavanone 3-hydroxylase-like protein gene SlF3HL by using transgenic tobacco. The expression of the gene was up-regulated under chilling (4 °C), heat (42 °C), salt (NaCl) and oxidative (H2O2) stresses. The transgenic plants that displayed high SlF3HL mRNA and protein levels showed higher flavonoid content than the WT plants. Moreover, the expression of three flavonoid biosynthesis-related structural genes, namely, chalcone synthase (CHS), chalcone isomerase (CHI) and flavonol synthase (FLS) was also higher in the transgenic plants than in the WT plants. Under chilling stress, the transgenic plants showed not only faster seed germination, better survival and growth, but also lower malondialdehyde (MDA) accumulation, relative electrical conductivity (REC) and H2O2 and O2(·-) levels compared with WT plants. These results suggested that SlF3HL stimulated flavonoid biosynthesis in response to chilling stress.

  8. 4-Coumaroyl coenzyme A 3-hydroxylase activity from cell cultures of Lithospermum erythrorhizon and its relationship to polyphenol oxidase.

    PubMed

    Wang, Z X; Li, S M; Löscher, R; Heide, L

    1997-11-15

    A 4-coumaroyl-CoA 3-hydroxylase activity was purified 4600-fold from cell cultures of Lithospermum erythrorhizon. The enzyme showed a molecular mass of 42,400 +/- 1700 Da in gel chromatography and required ascorbate, NADH, or NADPH as cofactors. 4-Coumaroyl-CoA, 4-coumarate, p-cresol, and several other phenolic substances, but not tyrosine, were accepted as substrates for the hydroxylation. Besides hydroxylase activity, the enzyme showed diphenol oxidase activity. Both activities were inhibited by diethyldithiocarbamate or beta-mercaptoethanol, although at different concentrations. The enzyme showed striking similarity to a 4-coumaroyl-glucose 3-hydroxylase from sweet potato (Ipomoe batatas) roots, which has reportedly been purified to homogeneity and identified as a specific enzyme of chlorogenic acid biosynthesis. Close examination and comparison to a commercially available polyphenol oxidase, however, suggest that the enzyme activities purified from both Lithospermum and sweet potato are polyphenol oxidases rather than specific enzymes of secondary metabolism.

  9. Cloning and characterization of a flavanone 3-hydroxylase gene from Saussurea medusa.

    PubMed

    Jin, Zhiping; Grotewold, Erich; Qu, Wenquan; Fu, Ghunxiang; Zhao, Dexiu

    2005-04-01

    Flavanone 3-hydroxylase (F3H) is a key enzyme in the flavonoid biosynthetic pathway, providing a branching point for the biosynthesis of different flavonoids, including the formation of 3-deoxy and 3-hydroxy flavonoids found in the silks of maize. Here, we report the cloning and characterization of a F3H gene (Smf3h) from a cDNA library derived from a red line callus of Saussurea medusa, a traditional Chinese medicinal plant. The cDNA contains a 1032 bp open reading frame (ORF) encoding a protein of 343 amino acid residues, a 149 bp long 5'untranslated regions (UTR) and a 163 bp long 3'UTR containing three putative polyadenylation signals (AATAAA) and an ATTTA element. The secondary structure of the mRNA predicted by MFOLD is very complex, suggesting a role in a post-transcriptional mechanism of regulation of Smf3h. The genomic structure of Smf3h includes four exons and three introns within the coding region, with all the splice donor/acceptor site sequences in accordance with the "GU-AG" consensus rule. The deduced SmF3H protein is 343 amino acid residues in length and has 40% and 39% identity and 60% and 58% similarity to the F3H of Arabidopsis and rice, respectively. Strikingly, the identity of SmF3H is higher to the H6H (hyoscyamine 3beta-hydroxylase, 45%) from Atropa belladonna. However, the analysis of the active center and the predicted protein secondary structure are more related to F3H than H6H. Together, our studies provide the first identification of a S. medusa flavonoid gene and its similarities to metabolic enzymes from other plants.

  10. Biotransformation of 4-halophenols to 4-halocatechols using Escherichia coli expressing 4-hydroxyphenylacetate 3-hydroxylase.

    PubMed

    Coulombel, Lydie; Nolan, Louise C; Nikodinovic, Jasmina; Doyle, Evelyn M; O'Connor, Kevin E

    2011-03-01

    Escherichia coli cells, expressing 4-hydroxyphenylacetate 3-hydroxylase, fully transformed 4-halogenated phenols to their equivalent catechols as single products in shaken flasks. 4-Fluorophenol was transformed at a rate 1.6, 1.8, and 3.4-fold higher than the biotransformation of 4-chloro-, 4-bromo-, and 4-iodo-phenol, respectively. A scale-up from shaken flask to a 5 L stirred tank bioreactor was undertaken to develop a bioprocess for the production of 4-substituted halocatechols at higher concentrations and scale. In a stirred tank reactor, the optimized conditions for induction of 4-HPA hydroxylase expression were at 37 °C for 3 h. The rate of biotransformation of 4-fluorophenol to 4-fluorocatechol by stirred tank bioreactor grown cells was the same at 1 and 4.8 mM (5.13 μmol/min/g CDW) once the ratio of biocatalyst (E. coli CDW) to substrate concentration (mM) was maintained at 2:1. At 10.8 mM 4-fluorophenol, the rate of 4-fluorocatechol formation decreased by 4.7-fold. However, the complete transformation of 1.3 g of 4-fluorophenol (10.8 mM) to 4-fluorocatechol was achieved within 7 h in a 1 L reaction volume. Similar to 4-fluorophenol, other 4-substituted halophenols were completely transformed to 4-halocatechols at 2 mM within a 1-2 h period. An increase in 4-halophenol concentration to 4.8 mM resulted in a 2.5-20-fold decrease in biotransformation efficiency depending on the substrate tested. Organic solvent extraction of the 4-halocatechol products followed by column chromatography resulted in the production of purified products with a final yield of between 33% and 38%.

  11. Molecular cloning and characterization of a flavanone 3-Hydroxylase gene from Artemisia annua L.

    PubMed

    Xiong, Shuo; Tian, Na; Long, Jinhua; Chen, Yuhong; Qin, Yu; Feng, Jinyu; Xiao, Wenjun; Liu, Shuoqian

    2016-08-01

    Flavonoids were found to synergize anti-malaria and anti-cancer compounds in Artemisia annua, a very important economic crop in China. In order to discover the regulation mechanism of flavonoids in Artemisia annua, the full length cDNA of flavanone 3-hydroxylase (F3H) were isolated from Artemisia annua for the first time by using RACE (rapid amplification of cDNA ends). The completed open read frame of AaF3H was 1095 bp and it encoded a 364-amino acid protein with a predicted molecular mass of 41.18 kDa and a pI of 5.67. The recombinant protein of AaF3H was expressed in E. coli BL21(DE3) as His-tagged protein, purified by Ni-NTA agrose affinity chromatography, and functionally characterized in vitro. The results showed that the His-tagged protein (AaF3H) catalyzed naringenin to dihydrokaempferol in the present of Fe(2+). The Km for naringenin was 218.03 μM. The optimum pH for AaF3H reaction was determined to be pH 8.5, and the optimum temperature was determined to be 35 °C. The AaF3H transcripts were found to be accumulated in the cultivar with higher level of flavonoids than that with lower level of flavonoids, which implied that AaF3H was a potential target for regulation of flavonoids biosynthesis in Artemisia annua through metabolic engineering.

  12. Sustained and selective suppression of intestinal cholesterol synthesis by Ro 48-8071, an inhibitor of 2,3-oxidosqualene:lanosterol cyclase, in the BALB/c mouse.

    PubMed

    Chuang, Jen-Chieh; Valasek, Mark A; Lopez, Adam M; Posey, Kenneth S; Repa, Joyce J; Turley, Stephen D

    2014-04-01

    The small intestine plays a fundamentally important role in regulating whole body cholesterol balance and plasma lipoprotein composition. This is articulated through the interplay of a constellation of genes that ultimately determines the net amount of chylomicron cholesterol delivered to the liver. Major advances in our insights into regulation of the cholesterol absorption pathway have been made using genetically manipulated mouse models and agents such as ezetimibe. One unresolved question is how a sustained pharmacological inhibition of intestinal cholesterol synthesis in vivo may affect cholesterol handling by the absorptive cells. Here we show that the lanosterol cyclase inhibitor, Ro 48-8071, when fed to BALB/c mice in a chow diet (20 mg/day/kg body weight), leads to a rapid and sustained inhibition (>50%) of cholesterol synthesis in the whole small intestine. Sterol synthesis was also reduced in the large intestine and stomach. In contrast, hepatic cholesterol synthesis, while markedly suppressed initially, rebounded to higher than baseline rates within 7 days. Whole body cholesterol synthesis, fractional cholesterol absorption, and fecal neutral and acidic sterol excretion were not consistently changed with Ro 48-8071 treatment. There were no discernible effects of this agent on intestinal histology as determined by H&E staining and the level of Ki67, an index of proliferation. The mRNA expression for multiple genes involved in intestinal cholesterol regulation including NPC1L1 was mostly unchanged although there was a marked rise in the mRNA level for the PXR target genes CYP3A11 and CES2A.

  13. Cloning and Characterization of a Flavonoid 3'-Hydroxylase Gene from Tea Plant (Camellia sinensis).

    PubMed

    Zhou, Tian-Shan; Zhou, Rui; Yu, You-Ben; Xiao, Yao; Li, Dong-Hua; Xiao, Bin; Yu, Oliver; Yang, Ya-Jun

    2016-02-22

    Tea leaves contain abundant flavan-3-ols, which include dihydroxylated and trihydroxylated catechins. Flavonoid 3'-hydroxylase (F3'H: EC 1.14.13.21) is one of the enzymes in the establishment of the hydroxylation pattern. A gene encoding F3'H, designated as CsF3'H, was isolated from Camellia sinensis with a homology-based cloning technique and deposited in the GenBank (GenBank ID: KT180309). Bioinformatic analysis revealed that CsF3'H was highly homologous with the characterized F3'Hs from other plant species. Four conserved cytochrome P450-featured motifs and three F3'H-specific conserved motifs were discovered in the protein sequence of CsF3'H. Enzymatic analysis of the heterologously expressed CsF3'H in yeast demonstrated that tea F3'H catalyzed the 3'-hydroxylation of naringenin, dihydrokaempferol and kaempferol. Apparent Km values for these substrates were 17.08, 143.64 and 68.06 μM, and their apparent Vmax values were 0.98, 0.19 and 0.44 pM·min(-1), respectively. Transcription level of CsF3'H in the new shoots, during tea seed germination was measured, along with that of other key genes for flavonoid biosynthesis using real-time PCR technique. The changes in 3',4'-flavan-3-ols, 3',4',5'-flavan-3-ols and flavan-3-ols, were consistent with the expression level of CsF3'H and other related genes in the leaves. In the study of nitrogen supply for the tea plant growth, our results showed the expression level of CsF3'H and all other tested genes increased in response to nitrogen depletion after 12 days of treatment, in agreement with a corresponding increase in 3',4'-catechins, 3',4',5'-catechins and flavan 3-ols content in the leaves. All these results suggest the importance of CsF3'H in the biosynthesis of 3',4'-catechins, 3',4',5'-catechins and flavan 3-ols in tea leaves.

  14. 46 CFR 111.105-40 - Additional requirements for RO/RO vessels.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... RO/RO vessels. (a) Each RO/RO vessel must meet ABS Steel Vessel Rules (incorporated by reference; see... 1 hazardous location. (c) Where the ventilation requirement of ABS Steel Vessel Rules section...

  15. CoRoTlog

    NASA Astrophysics Data System (ADS)

    Plasson, Ph.

    2006-11-01

    LESIA, in close cooperation with CNES, DLR and IWF, is responsible for the tests and validation of the CoRoT instrument digital process unit which is made up of the BEX and DPU assembly. The main part of the work has consisted in validating the DPU software and in testing the BEX/DPU coupling. This work took more than two years due to the central role of the software tested and its technical complexity. The first task, in the validation process, was to carry out the acceptance tests of the DPU software. These tests consisted in checking each of the 325 requirements identified in the URD (User Requirements Document) and were played in a configuration using the DPU coupled to a BEX simulator. During the acceptance tests, all the transversal functionalities of the DPU software, like the TC/TM management, the state machine management, the BEX driving, the system monitoring or the maintenance functionalities were checked in depth. The functionalities associated with the seismology and exoplanetology processing, like the loading of window and mask descriptors or the configuration of the service execution parameters, were also exhaustively tested. After having validated the DPU software against the user requirements using a BEX simulator, the following step consisted in coupling the DPU and the BEX in order to check that the formed unit worked correctly and met the performance requirements. These tests were conducted in two phases: the first one was devoted to the functional aspects and the tests of interface, the second one to the performance aspects. The performance tests were based on the use of the DPU software scientific services and on the use of full images representative of a realistic sky as inputs. These tests were also based on the use of a reference set of windows and parameters, which was provided by the scientific team and was representative, in terms of load and complexity, of the one that could be used during the observation mode of the CoRoT instrument

  16. An active hAT transposable element causing bud mutation of carnation by insertion into the flavonoid 3'-hydroxylase gene.

    PubMed

    Momose, Masaki; Nakayama, Masayoshi; Itoh, Yoshio; Umemoto, Naoyuki; Toguri, Toshihiro; Ozeki, Yoshihiro

    2013-04-01

    The molecular mechanisms underlying spontaneous bud mutations, which provide an important breeding tool in carnation, are poorly understood. Here we describe a new active hAT type transposable element, designated Tdic101, the movement of which caused a bud mutation in carnation that led to a change of flower color from purple to deep pink. The color change was attributed to Tdic101 insertion into the second intron of F3'H, the gene for flavonoid 3'-hydroxylase responsible for purple pigment production. Regions on the deep pink flowers of the mutant can revert to purple, a visible phenotype of, as we show, excision of the transposable element. Sequence analysis revealed that Tdic101 has the characteristics of an autonomous element encoding a transposase. A related, but non-autonomous element dTdic102 was found to move in the genome of the bud mutant as well. Its mobilization might be the result of transposase activities provided by other elements such as Tdic101. In carnation, therefore, the movement of transposable elements plays an important role in the emergence of a bud mutation.

  17. Hydroxytyrosol from tyrosol using hydroxyphenylacetic acid-induced bacterial cultures and evidence of the role of 4-HPA 3-hydroxylase.

    PubMed

    Liebgott, Pierre-Pol; Amouric, Agnès; Comte, Alexia; Tholozan, Jean-Luc; Lorquin, Jean

    2009-12-01

    Hydroxytyrosol (HTyr) is a potent natural antioxidant found in olive mill wastewaters. Bacterial conversion of 4-tyrosol (2-(4-hydroxyphenyl)-ethanol) to HTyr was reported in a limited number of bacterial species including Pseudomonas aeruginosa. In this work, we studied this conversion, taking as a model the newly isolated Halomonas sp. strain HTB24. It was first hypothesized that the enzyme responsible for 4-tyrosol hydroxylation in HTyr was a 4-hydroxyphenylacetic acid 3-hydroxylase (HPAH, EC 1.14.13.3), previously known to convert 4-hydroxyphenylacetic acid (4-HPA) into 3,4-dihydroxyphenylacetic acid (3,4-DHPA) in P. aeruginosa. Cloning and expression of hpaB (oxygenase component) and hpaC (reductase component) genes from P. aeruginosa confirmed this hypothesis. Furthermore, using cultures of HTB24 containing 4-tyrosol, it was shown that 4-HPA accumulation preceded 4-tyrosol hydroxylation. We further demonstrated that the synthesis of HPAH activity was induced by 4-HPA, with the latter compound being formed from 4-tyrosol oxidation by aryl-dehydrogenases. Interestingly, similar results were obtained with other 4-HPA-induced bacteria, including P. aeruginosa, Serratia marcescens, Escherichia coli, Micrococcus luteus and other Halomonas, thus demonstrating general hydroxylating activity of 4-tyrosol by the HPAH enzyme. E. coli W did not have aryl-dehydrogenase activity and hence were unable to oxidize 4-tyrosol to 4-HPA and HTyr to 3,4-DHPA, making this bacterium a good candidate for achieving better HTyr production.

  18. A single amino acid substitution (F363I) converts the regiochemistry of the spearmint (−)-limonene hydroxylase from a C6- to a C3-hydroxylase

    PubMed Central

    Schalk, Michel; Croteau, Rodney

    2000-01-01

    The essential oils of peppermint and spearmint are distinguished by the position of oxygenation on the constituent p-menthane monoterpenes. Peppermint produces monoterpenes bearing an oxygen at C3, whereas spearmint produces monoterpenes bearing an oxygen at C6. Branching of the monoterpene biosynthetic pathways in these species is determined by two distinct cytochrome P450s that catalyze the regiospecific hydroxylation of (−)-4S-limonene at C3 or C6 exclusively. cDNAs encoding the limonene-3-hydroxylase from peppermint and the limonene-6-hydroxylase from spearmint have been isolated, shown to be 70% identical at the amino acid level, and functionally expressed. A combination of domain swapping and reciprocal site-directed mutagenesis between these two enzymes demonstrated that the exchange of a single residue (F363I) in the spearmint limonene-6-hydroxylase led to complete conversion to the regiospecificity and catalytic efficiency of the peppermint limonene-3-hydroxylase. PMID:11050228

  19. Purification, characterization, and directed evolution study of a vitamin D{sub 3} hydroxylase from Pseudonocardia autotrophica

    SciTech Connect

    Fujii, Yoshikazu; Kabumoto, Hiroki; Nishimura, Kenji; Fujii, Tadashi; Yanai, Satoshi; Takeda, Koji; Tamura, Noriko; Arisawa, Akira; Tamura, Tomohiro

    2009-07-24

    Vitamin D{sub 3} (VD{sub 3}) is a fat-soluble prohormone that plays a crucial role in bone metabolism, immunity, and control of cell proliferation and cell differentiation in mammals. The actinomycete Pseudonocardia autotrophica is capable of bioconversion of VD{sub 3} into its physiologically active forms, namely, 25(OH)VD{sub 3} or 1{alpha},25(OH){sub 2}VD{sub 3}. In this study, we isolated and characterized Vdh (vitamin D{sub 3} hydroxylase), which hydroxylates VD{sub 3} from P. autotrophica NBRC 12743. The vdh gene encodes a protein containing 403 amino acids with a molecular weight of 44,368 Da. This hydroxylase was found to be homologous with the P450 belonging to CYP107 family. Vdh had the same ratio of the V{sub max} values for VD{sub 3} 25-hydroxylation and 25(OH)VD{sub 3} 1{alpha}-hydroxylation, while other enzymes showed preferential regio-specific hydroxylation on VD{sub 3}. We characterized a collection of Vdh mutants obtained by random mutagenesis and obtained a Vdh-K1 mutant by the combination of four amino acid substitutions. Vdh-K1 showed one-order higher VD{sub 3} 25-hydroxylase activity than the wild-type enzyme. Biotransformation of VD{sub 3} into 25(OH)VD{sub 3} was successfully accomplished with a Vdh-expressed recombinant strain of actinobacterium Rhodococcus erythropolis. Vdh may be a useful enzyme for the production of physiologically active forms of VD{sub 3} by a single cytochrome P450.

  20. Gibberellins regulate the transcription of the continuous flowering regulator, RoKSN, a rose TFL1 homologue

    PubMed Central

    Foucher, Fabrice

    2012-01-01

    The role of gibberellins (GAs) during floral induction has been widely studied in the annual plant Arabidopsis thaliana. Less is known about this control in perennials. It is thought that GA is a major regulator of flowering in rose. In spring, low GA content may be necessary for floral initiation. GA inhibited flowering in once-flowering roses, whereas GA did not block blooming in continuous-flowering roses. Recently, RoKSN, a homologue of TFL1, was shown to control continuous flowering. The loss of RoKSN function led to continuous flowering behaviour. The objective of this study was to understand the molecular control of flowering by GA and the involvement of RoKSN in this inhibition. In once-flowering rose, the exogenous application of GA3 in spring inhibited floral initiation. Application of GA3 during a short period of 1 month, corresponding to the floral transition, was sufficient to inhibit flowering. At the molecular level, RoKSN transcripts were accumulated after GA3 treatment. In spring, this accumulation is correlated with floral inhibition. Other floral genes such as RoFT, RoSOC1, and RoAP1 were repressed in a RoKSN-dependent pathway, whereas RoLFY and RoFD repression was RoKSN independent. The RoKSN promoter contained GA-responsive cis-elements, whose deletion suppressed the response to GA in a heterologous system. In summer, once-flowering roses did not flower even after exogenous application of a GA synthesis inhibitor that failed to repress RoKSN. A model is presented for the GA inhibition of flowering in spring mediated by the induction of RoKSN. In summer, factors other than GA may control RoKSN. PMID:23175671

  1. Characterisation of RO fouling in an integrated MBR/RO system for wastewater reuse.

    PubMed

    Moreno, J; Monclús, H; Stefani, M; Cortada, E; Aumatell, J; Adroer, N; De Lamo-Castellví, S; Comas, J

    2013-01-01

    Membrane filtration has gradually gained acceptance as the preferred pre-treatment for reverse osmosis (RO). In this paper, an integrated membrane bioreactor (MBR)/RO system for wastewater reuse treating real sewage water has been evaluated and the RO fouling has been characterised. The MBR achieved low values of organic matter, total nitrogen, PO(4)(3-), total organic carbon, turbidity and conductivity. Filtration with two different RO commercial membranes was performed after the MBR pre-treatment and the same average fouling rate (0.08 bar day(-1)) was noted. These results gained from the characterisation of the high quality MBR/RO permeate show its potential for water reuse. Inorganic precipitation appears to be the predominant form of fouling in the RO membranes. Calcium phosphate and alumino-silicates were identified by a scanning electron microscope combined with an energy dispersive X-ray and polysaccharides, amide and aliphatic structures were detected with attenuated total reflection infrared microspectroscopy.

  2. Expression and enzymatic activity of phenylalanine ammonia-lyase and p-coumarate 3-hydroxylase in mango (Mangifera indica 'Ataulfo') during ripening.

    PubMed

    Palafox-Carlos, H; Contreras-Vergara, C A; Muhlia-Almazán, A; Islas-Osuna, M A; González-Aguilar, G A

    2014-05-16

    Phenylalanine ammonia lyase (PAL) and p-coumarate 3-hydroxylase (C3H) are key enzymes in the phenylpropanoid pathway. The relative expression of PAL and C3H was evaluated in mango fruit cultivar 'Ataulfo' in four ripening stages (RS1, RS2, RS3, and RS4) by quantitative polymerase chain reaction. In addition, enzyme activity of PAL and C3H was determined in mango fruits during ripening. The PAL levels were downregulated at the RS2 and RS3 stages, while C3H levels were upregulated in fruits only at RS3. The enzyme activity of PAL followed a pattern that was different from that of the PAL expression, thus suggesting regulation at several levels. For C3H, a regulation at the transcriptional level is suggested because a similar pattern was revealed by its activity and transcript level. In this study, the complexity of secondary metabolite biosynthesis regulation is emphasized because PAL and C3H enzymes are involved in the biosynthesis of several secondary metabolites that are active during all mango ripening stages.

  3. Differential expression of flavonoid 3'-hydroxylase during fruit development establishes the different B-ring hydroxylation patterns of flavonoids in Fragaria × ananassa and Fragaria vesca.

    PubMed

    Thill, Jana; Miosic, Silvija; Gotame, Tek Prasad; Mikulic-Petkovsek, Maja; Gosch, Christian; Veberic, Robert; Preuss, Anja; Schwab, Wilfried; Stampar, Franci; Stich, Karl; Halbwirth, Heidi

    2013-11-01

    Flavonoid 3'-hydroxylase (F3'H) was studied for the first time in different Fragaria species. The cDNA clones isolated from unripe and ripe fruits of Fragaria x ananassa (garden strawberry) and Fragaria vesca (wild strawberry) showed high similarity (99% at the amino acid level) to the publically available F. vesca genome sequence and no significant differences could be identified between species and developmental stages of the fruits. In contrast, the genomic F3'H clones showed differences in the non-coding regions and 5'-flanking elements. The recombinant F3'Hs were functionally active and showed high specificity for naringenin, dihydrokaempferol, and kaempferol, whereas apigenin was only a minor substrate. During fruit development, a clear difference in the F3'H expression was observed between F. × ananassa and F. vesca. While a drastic decline of F3'H expression occurred during fruit ripening in F. × ananassa, F3'H in F. vesca was highly expressed in all stages. This was reflected by the anthocyanin composition, which showed a prevalence of pelargonidin in ripe fruits of F. × ananassa, whereas F. vesca had a high content of cyanidin. Screening of 17 berry species for their anthocyanin and flavonol composition showed that the prevalence of monohydroxylated anthocyanins makes garden strawberry unique among all other fruit species indicating that selection of bright red color during strawberry breeding, which consumers typically associate with freshness and ripeness, has selected phenotypes with a special biochemical background.

  4. Co-downregulation of the hydroxycinnamoyl-CoA:shikimate hydroxycinnamoyl transferase and coumarate 3-hydroxylase significantly increases cellulose content in transgenic alfalfa (Medicago sativa L.).

    PubMed

    Tong, Zongyong; Li, Heng; Zhang, Rongxue; Ma, Lei; Dong, Jiangli; Wang, Tao

    2015-10-01

    Lignin is a component of the cell wall that is essential for growth, development, structure and pathogen resistance in plants, but high lignin is an obstacle to the conversion of cellulose to ethanol for biofuel. Genetically modifying lignin and cellulose contents can be a good approach to overcoming that obstacle. Alfalfa (Medicago sativa L.) is rich in lignocellulose biomass and used as a model plant for the genetic modification of lignin in this study. Two key enzymes in the lignin biosynthesis pathway-hydroxycinnamoyl -CoA:shikimate hydroxycinnamoyl transferase (HCT) and coumarate 3-hydroxylase (C3H)-were co-downregulated. Compared to wild-type plants, the lignin content in the modified strain was reduced by 38%, cellulose was increased by 86.1%, enzyme saccharification efficiency was increased by 10.9%, and cell wall digestibility was increased by 13.0%. The modified alfalfa exhibited a dwarf phenotype, but normal above ground biomass. This approach provides a new strategy for reducing lignin and increasing cellulose contents and creates a new genetically modified crop with enhanced value for biofuel.

  5. Cloning and characterization of Lonicera japonica p-coumaroyl ester 3-hydroxylase which is involved in the biosynthesis of chlorogenic acid.

    PubMed

    Pu, Gaobin; Wang, Peng; Zhou, Bingqian; Liu, Zhenhua; Xiang, Fengning

    2013-01-01

    Lonicera japonica is used in Chinese medicine as a source of antioxidants, primarily flavonoids, and a phenolic acid chlorogenic acid (CGA). Here we report the isolation and characterization of the full-length cDNA of LjC3H, a gene encoding p-coumaroyl ester 3-hydroxylase, an enzyme involved in CGA synthesis. Phylogenetic analysis indicated that is protein belongs to the CYP98A subfamily, and homology modeling revealed that its structure resembles that of other cytochrome P450 family proteins. Southern blot analysis indicated that more than one copy of sequences homologous to LjC3H is present in the L. japonica genome. Heterologous expression of LjC3H cDNA in Escherichia coli allowed an in vitro assay of LjC3H to be performed. This experiment revealed that the enzyme favors p-coumaroylshikimate over p-coumaroylquinate as substrate. LjC3H transcript abundance was increased both by treatment of the leaves with methyl jasmonate and by exposure to UV-B radiation. The CGA levels in the leaves of L. japonica were positively correlated with LjC3H transcript abundance.

  6. Expression of Flavone Synthase II and Flavonoid 3'-Hydroxylase Is Associated with Color Variation in Tan-Colored Injured Leaves of Sorghum.

    PubMed

    Mizuno, Hiroshi; Yazawa, Takayuki; Kasuga, Shigemitsu; Sawada, Yuji; Kanamori, Hiroyuki; Ogo, Yuko; Hirai, Masami Yokota; Matsumoto, Takashi; Kawahigashi, Hiroyuki

    2016-01-01

    Sorghum (Sorghum bicolor L. Moench) exhibits various color changes in injured leaves in response to cutting stress. Here, we aimed to identify key genes for the light brown and dark brown color variations in tan-colored injured leaves of sorghum. For this purpose, sorghum M36001 (light brown injured leaves), Nakei-MS3B (purple), and a progeny, #7 (dark brown), from Nakei-MS3B × M36001, were used. Accumulated pigments were detected by using high-performance liquid chromatography: M36001 accumulated only apigenin in its light brown leaves; #7 accumulated both luteolin and a small amount of apigenin in its dark brown leaves, and Nakei-MS3B accumulated 3-deoxyanthocyanidins (apigeninidin and luteolinidin) in its purple leaves. Apigenin or luteolin glucoside derivatives were also accumulated, in different proportions. Differentially expressed genes before and after cutting stress were identified by using RNA sequencing (RNA-seq). Integration of our metabolic and RNA-seq analyses suggested that expression of only flavone synthase II (FNSII) led to the synthesis of apigenin in M36001, expression of both FNSII and flavonoid 3'-hydroxylase (F3'H) led to the synthesis of apigenin and luteolin in #7, and expression of both flavanone 4-reductase and F3'H led to the synthesis of 3-deoxyanthocyanidins in Nakei-MS3B. These results suggest that expression of FNSII is related to the synthesis of flavones (apigenin and luteolin) and the expression level of F3'H is related to the balance of apigenin and luteolin. Expression of FNSII and F3'H is thus associated with dark or light brown coloration in tan-colored injured leaves of sorghum.

  7. Expression of genes encoding chalcone synthase, flavanone 3-hydroxylase and dihydroflavonol 4-reductase correlates with flavanol accumulation during heartwood formation in Juglans nigra.

    PubMed

    Beritognolo, Isacco; Magel, Elisabeth; Abdel-Latif, Amani; Charpentier, Jean-Paul; Jay-Allemand, Christian; Breton, Christian

    2002-04-01

    Heartwood formation is generally characterized by the accumulation of phenolic substances that increase the natural color and durability of wood. Although there is evidence that these substances are synthesized in aging sapwood cells, little is known about heartwood formation at the molecular level. We monitored seasonal changes in flavanol concentration across the stems of 23-year-old Juglans nigra L. trees by sampling growth rings extending from the differentiating xylem to the heartwood. We also analyzed expression of phenylpropanoid and flavonoid structural genes in these samples. In the sapwood-heartwood transition zone, flavanol accumulation was correlated with the transcription levels of the chalcone synthase (CHS) and flavanone 3-hydroxylase (F3H) genes. We also observed correlations between flavanol accumulation and the amount of dihydroflavonol 4-reductase (DFR) gene transcript in October, January and May. Although transcription of phenylalanine ammonia-lyase (PAL) and 4-coumarate:CoA ligase (4CL) genes did not correlate with flavanol accumulation, PAL genes were strongly expressed in the transition zone of samples collected in autumn, suggesting that their transcription in these tissues contributes to phenolic biosynthesis. Western immunoblotting showed that accumulation of CHS protein correlated with the amount of CHS gene transcript, whereas accumulation of PAL protein did not correlate with the the transcription levels PAL genes. Preliminary analyses revealed that PAL and CHS activities were higher in the transition zone than in the inner sapwood in autumn, winter, and spring. Thus, CHS activity could be regulated mainly at the transcriptional level, whereas post-translational modifications could modulate PAL activity. We conclude that flavanols are synthesized de novo in J. nigra sapwood cells that are undergoing transformation to heartwood.

  8. Regulation of flavanone 3-hydroxylase gene involved in the flavonoid biosynthesis pathway in response to UV-B radiation and drought stress in the desert plant, Reaumuria soongorica.

    PubMed

    Liu, Meiling; Li, Xinrong; Liu, Yubing; Cao, Bo

    2013-12-01

    Flavonoid are known to have various functions in growth, development, reproduction, and also involved in diverse stress responses in plants. However, little is known about the roles of the key enzymes in the flavonoid biosynthetic pathway in response to environmental stress, such as UV-B radiation and drought. To understand this problem, we investigated the participation of flavanone 3-hydroxylase gene (F3H), a key enzyme in flavonoid biosynthetic pathway under UV-B radiation and drought stress in the desert plant Reaumuria soongorica. A novel cDNA sequence, named as RsF3H, was isolated from R. soongorica. The deduced amino acids showed high identities to other F3Hs. A phylogenetic analysis indicated that RsF3H appeared to be most homologous to F3H from Malus domestica (MdF3H). RsF3H protein structure contained all five conserved motifs for 2-oxoglutarate-dependent dioxygenases (2-ODDs) and an Arg-X-Ser motif, all of which were also found in other F3Hs. Quantitative real-time RT-PCR analysis showed that there was a rapid increase in gene expression of RsF3H under stress. Both UV-B radiation and drought stress induced an increase in RsF3H enzyme activity and the accumulation of the products in the flavonoid biosynthetic pathway (total flavonoid and anthocyanin). The antioxidant ability (inhibition of lipid oxidation) of total flavonoid was enhanced during this study. The results suggested that one explanation of the stress tolerance of R. soongorica may be a combination of an increase in RsF3H gene expression, RsF3H enzyme activity and the anti-oxidative ability of the metabolic end products in the flavonoid biosynthetic pathway in response to UV-B radiation and drought.

  9. Identification of the flavonoid 3'-hydroxylase and flavonoid 3',5'-hydroxylase genes from Antarctic moss and their regulation during abiotic stress.

    PubMed

    Liu, Shenghao; Ju, Jianfang; Xia, Guangmin

    2014-06-10

    Flavonoids are ubiquitous plant secondary metabolites, and their hydroxylation pattern determines their color, stability, and antioxidant capacity. The hydroxylation pattern of the B-ring of flavonoids is determined by the activity of two members of cytochrome P450 protein (P450) family, the flavonoid 3'-hydroxylase (F3'H) and flavonoid 3',5'-hydroxylase (F3',5'H). However, they are still not well documented in lower plants such as bryophytes. We report the identification of gene encoding F3'H, F3',5'H from Antarctic moss Pohlia nutans and their transcriptional regulation under different stress conditions. Totally, sixteen cDNAs were isolated from P. nutans by RT-PCR and RACE techniques, all of which were predicted to code for F3'Hs or F3',5'Hs based on their annotations of Blast results. Amino acid alignment showed that they possessed the featured conserved domains of flavonoid hydroxylase, including proline-rich "hinge" region, EXXR motif, oxygen binding pocket motif, heme binding domain and substrate recognition sites. Phylogenetic analysis indicated that moss F3'Hs and F3',5'Hs were highly conserved and have independent evolution from the monocots, dicots and ferns. Meanwhile, real-time PCR analysis revealed that the expression profiling of flavonoid hydroxylase genes was influenced by diverse abiotic stresses including cold, salinity, drought or UV-B radiation and plant hormone abscisic acid (ABA) or jasmonic acid (JA) treatment. Since 3',4',5'-hydroxylated flavonoid-derivatives may serve a multitude of functions, including antioxidant activity and UV filters, the evolution and expression profile of flavonoid hydroxylase probably reflect the adaptive value of Antarctic moss in the acclimation of polar environment.

  10. Characterization of 4-Hydroxyphenylacetate 3-Hydroxylase (HpaB) of Escherichia coli as a Reduced Flavin Adenine Dinucleotide-Utilizing Monooxygenase

    PubMed Central

    Xun, Luying; Sandvik, Erik R.

    2000-01-01

    4-Hydroxyphenylacetate 3-hydroxylase (HpaB and HpaC) of Escherichia coli W has been reported as a two-component flavin adenine dinucleotide (FAD)-dependent monooxygenase that attacks a broad spectrum of phenolic compounds. However, the function of each component in catalysis is unclear. The large component (HpaB) was demonstrated here to be a reduced FAD (FADH2)-utilizing monooxygenase. When an E. coli flavin reductase (Fre) having no apparent homology with HpaC was used to generate FADH2 in vitro, HpaB was able to use FADH2 and O2 for the oxidation of 4-hydroxyphenylacetate. HpaB also used chemically produced FADH2 for 4-hydroxyphenylacetate oxidation, further demonstrating that HpaB is an FADH2-utilizing monooxygenase. FADH2 generated by Fre was rapidly oxidized by O2 to form H2O2 in the absence of HpaB. When HpaB was included in the reaction mixture without 4-hydroxyphenylacetate, HpaB bound FADH2 and transitorily protected it from rapid autoxidation by O2. When 4-hydroxyphenylacetate was also present, HpaB effectively competed with O2 for FADH2 utilization, leading to 4-hydroxyphenylacetate oxidation. With sufficient amounts of HpaB in the reaction mixture, FADH2 produced by Fre was mainly used by HpaB for the oxidation of 4-hydroxyphenylacetate. At low HpaB concentrations, most FADH2 was autoxidized by O2, causing uncoupling. However, the coupling of the two enzymes' activities was increased by lowering FAD concentrations in the reaction mixture. A database search revealed that HpaB had sequence similarities to several proteins and gene products involved in biosynthesis and biodegradation in both bacteria and archaea. This is the first report of an FADH2-utilizing monooxygenase that uses FADH2 as a substrate rather than as a cofactor. PMID:10653707

  11. Isolation and molecular characterisation of flavonoid 3'-hydroxylase and flavonoid 3', 5'-hydroxylase genes from a traditional Chinese medicinal plant, Epimedium sagittatum.

    PubMed

    Huang, Wenjun; Sun, Wei; Wang, Ying

    2012-04-10

    The epimedii herb, a traditional Chinese medicinal plant, has significant pharmacological effects on human health. The bioactive components in the herb (Epimedium sagittatum (Sieb. et Zucc.) Maxim) are mainly prenylated flavonol glycosides, which are end-products of the flavonoid biosynthetic pathway. This has not been clearly elucidated until recently. The genes encoding flavonoid 3'-hydroxylase (F3'H) and flavonoid 3', 5'-hydroxylase (F3'5'H) involved in the flavonoid biosynthetic pathway, designated as EsF3'H and EsF3'5'H, were isolated from E. sagittatum using a homology-based cloning method and deposited in the GenBank databases (GenBank ID: HM011054 and HM011055), respectively. EsF3'H and EsF3'5'H proteins shared high homology with other plant-specific flavonoid hydroxylases and were clustered into the CYP75B and CYP75A group, respectively. In addition, four conserved cytochrome P450-featured motifs were found in the amino acid sequences of both genes. Transcription levels of both genes were detected in all tissues tested and were high in most of the pigmented tissues. Moreover, the expression levels of both EsF3'H and EsF3'5'H correlated positively with the anthocyanin accumulation pattern in leaves from E. sagittatum. The cloning and molecular characterisation of EsF3'H and EsF3'5'H genes will accelerate progress in the study of the flavonoid biosynthetic pathway to elucidate the molecular mechanisms of the biosynthesis of the bioactive components in E. sagittatum.

  12. Transcriptome Analysis Reveals Key Flavonoid 3'-Hydroxylase and Flavonoid 3',5'-Hydroxylase Genes in Affecting the Ratio of Dihydroxylated to Trihydroxylated Catechins in Camellia sinensis.

    PubMed

    Wei, Kang; Wang, Liyuan; Zhang, Chengcai; Wu, Liyun; Li, Hailin; Zhang, Fen; Cheng, Hao

    2015-01-01

    The ratio of dihydroxylated to trihydroxylated catechins (RDTC) is an important indicator of tea quality and biochemical marker for the study of genetic diversity. It is reported to be under genetic control but the underlying mechanism is not well understood. Flavonoid 3'-hydroxylase (F3'H) and flavonoid 3',5'-hydroxylase (F3'5'H) are key enzymes involved in the formation of dihydroxylated and trihydroxylated catechins. The transcriptome and HPLC analysis of tea samples from Longjing43 and Zhonghuang2 under control and shading treatment were performed to assess the F3'H and F3'5'H genes that might affect RDTC. A total of 74.7 million reads of mRNA seq (2×101bp) data were generated. After de novo assembly, 109,909 unigenes were obtained, and 39,982 of them were annotated using 7 public databases. Four key F3'H and F3'5'H genes (including CsF3'5'H1, CsF3'H1, CsF3'H2 and CsF3'H3) were identified to be closely correlated with RDTC. Shading treatment had little effect on RDTC, which was attributed to the stable expression of these key F3'H and F3'5'H genes. The correlation of the coexpression of four key genes and RDTC was further confirmed among 13 tea varieties by real time PCR and HPLC analysis. The coexpression of three F3'H genes and a F3'5'H gene may play a key role in affecting RDTC in Camellia sinensis. The current results may establish valuable foundation for further research about the mechanism controlling catechin composition in tea.

  13. Ro(SS-A) and anti-Ro(SS-A): an update.

    PubMed

    Sibilia, J

    1998-01-01

    Anti-Ro/SSA antibodies are the antinuclear antibodies most commonly found in everyday clinical practice and are closely associated with Sjögren's syndrome, systemic lupus erythematosus and neonatal lupus. They play a pathogenic role in a variety of clinical manifestations, including skin lesions and neonatal lupus heart block. Autoantibodies to Ro(SS-A) recognize a ribonucleoprotein complex composed of small single-stranded RNAs (hYRNAs) and of one or more peptides. Four molecular forms of this complex have been differentiated based on the nature of the peptide: a lymphocyte and an erythrocyte Ro with a 60 kDa peptide, a lymphocyte Ro with a 52 kDa peptide and an erythrocyte Ro with a 54 kDa peptide. The Ro complex is found in most tissues and cells (erythrocytes, platelets), with differences in structure and quantity across tissues, species and embryonic development stages. Although its function remains unknown, its ability to bind nucleic acids and the fact that it shares homologies with gene regulation proteins suggest that it may participate in RNA transcription processes. A number of environmental factors (exposure to ultraviolet radiation, viral infections) may cause translocation of the Ro complex to nucleocytoplasmic and membrane sites where it is not normally found, thereby leading to the development of autoimmunity. The structure of the Ro(SS-A)-hYRNA complex and the development of autoimmunity are currently the focus of active research efforts that can be expected to improve our understanding of the clinical manifestations directly related to anti-Ro(SS-A) antibodies.

  14. Allele-specific marker development and selection efficiencies for both flavonoid 3'-hydroxylase and flavonoid 3',5'-hydroxylase genes in soybean subgenus soja.

    PubMed

    Guo, Yong; Qiu, Li-Juan

    2013-06-01

    Color is one of the phenotypic markers mostly used to study soybean (Glycine max L. Merr.) genetic, molecular and biochemical processes. Two P450-dependent mono-oxygenases, flavonoid 3'-hydroxylase (F3'H; EC1.14.3.21) and flavonoid 3',5'-hydroxylase (F3'5'H, EC1.14.13.88), both catalyzing the hydroxylation of the B-ring in flavonoids, play an important role in coloration. Previous studies showed that the T locus was a gene encoding F3'H and the W1 locus co-segregated with a gene encoding F3'5'H in soybean. These two genetic loci have identified to control seed coat, flower and pubescence colors. However, the allelic distributions of both F3'H and F3'5'H genes in soybean were unknown. In this study, three novel alleles were identified (two of four alleles for GmF3'H and one of three alleles for GmF3'5'H). A set of gene-tagged markers was developed and verified based on the sequence diversity of all seven alleles. Furthermore, the markers were used to analyze soybean accessions including 170 cultivated soybeans (G. max) from a mini core collection and 102 wild soybeans (G. soja). For both F3'H and F3'5'H, the marker selection efficiencies for pubescence color and flower color were determined. The results showed that one GmF3'H allele explained 92.2 % of the variation in tawny and two gmf3'h alleles explained 63.8 % of the variation in gray pubescence colors. In addition, two GmF3'5'H alleles and one gmF3'5'h allele explained 94.0 % of the variation in purple and 75.3 % in white flowers, respectively. By the combination of the two loci, seed coat color was determined. In total, 90.9 % of accessions possessing both the gmf3'h-b and gmf3'5'h alleles had yellow seed coats. Therefore, seed coat colors are controlled by more than two loci.

  15. Inhibitory Effects of Cytosolic Ca2+ Concentration by Ginsenoside Ro Are Dependent on Phosphorylation of IP3RI and Dephosphorylation of ERK in Human Platelets

    PubMed Central

    Kwon, Hyuk-Woo; Shin, Jung-Hae; Lee, Dong-Ha; Park, Hwa-Jin

    2015-01-01

    Intracellular Ca2+ ([Ca2+]i) is platelet aggregation-inducing molecule and is involved in activation of aggregation associated molecules. This study was carried out to understand the Ca2+-antagonistic effect of ginsenoside Ro (G-Ro), an oleanane-type saponin in Panax ginseng. G-Ro, without affecting leakage of lactate dehydrogenase, dose-dependently inhibited thrombin-induced platelet aggregation, and the half maximal inhibitory concentration was approximately 155 μM. G-Ro inhibited strongly thrombin-elevated [Ca2+]i, which was strongly increased by A-kinase inhibitor Rp-8-Br-cAMPS compared to G-kinase inhibitor Rp-8-Br-cGMPS. G-Ro increased the level of cAMP and subsequently elevated the phosphorylation of inositol 1, 4, 5-triphosphate receptor I (IP3RI) (Ser1756) to inhibit [Ca2+]i mobilization in thrombin-induced platelet aggregation. Phosphorylation of IP3RI (Ser1756) by G-Ro was decreased by PKA inhibitor Rp-8-Br-cAMPS. In addition, G-Ro inhibited thrombin-induced phosphorylation of ERK 2 (42 kDa), indicating inhibition of Ca2+ influx across plasma membrane. We demonstrate that G-Ro upregulates cAMP-dependent IP3RI (Ser1756) phosphorylation and downregulates phosphorylation of ERK 2 (42 kDa) to decrease thrombin-elevated [Ca2+]i, which contributes to inhibition of ATP and serotonin release, and p-selectin expression. These results indicate that G-Ro in Panax ginseng is a beneficial novel Ca2+-antagonistic compound and may prevent platelet aggregation-mediated thrombotic disease. PMID:26355658

  16. ACE inhibitors

    MedlinePlus

    ... In: Mann DL, Zipes DP, Libby P, Bonow RO, Braunwald E, eds. Braunwald's Heart Disease: A Textbook ... In: Mann DL, Zipes DP, Libby P, Bonow RO, Braunwald E, eds. Braunwald's Heart Disease: A Textbook ...

  17. Down-regulation of p-coumaroyl quinate/shikimate 3'-hydroxylase (C3'H) and cinnamate 4-hydroxylase (C4H) genes in the lignin biosynthetic pathway of Eucalyptus urophylla x E. grandis leads to improved sugar release

    DOE PAGES

    Sykes, Robert W.; Gjersing, Erica L.; Foutz, Kirk; ...

    2015-08-27

    In this study, lignocellulosic materials provide an attractive replacement for food-based crops used to produce ethanol. Understanding the interactions within the cell wall is vital to overcome the highly recalcitrant nature of biomass. One factor imparting plant cell wall recalcitrance is lignin, which can be manipulated by making changes in the lignin biosynthetic pathway. In this study, eucalyptus down-regulated in expression of cinnamate 4-hydroxylase (C4H, EC 1.14.13.11) or p-coumaroyl quinate/shikimate 3'-hydroxylase (C3'H, EC 1.14.13.36) were evaluated for cell wall composition and reduced recalcitrance.

  18. AstRoMap European Astrobiology Roadmap.

    PubMed

    Horneck, Gerda; Walter, Nicolas; Westall, Frances; Grenfell, John Lee; Martin, William F; Gomez, Felipe; Leuko, Stefan; Lee, Natuschka; Onofri, Silvano; Tsiganis, Kleomenis; Saladino, Raffaele; Pilat-Lohinger, Elke; Palomba, Ernesto; Harrison, Jesse; Rull, Fernando; Muller, Christian; Strazzulla, Giovanni; Brucato, John R; Rettberg, Petra; Capria, Maria Teresa

    2016-03-01

    The European AstRoMap project (supported by the European Commission Seventh Framework Programme) surveyed the state of the art of astrobiology in Europe and beyond and produced the first European roadmap for astrobiology research. In the context of this roadmap, astrobiology is understood as the study of the origin, evolution, and distribution of life in the context of cosmic evolution; this includes habitability in the Solar System and beyond. The AstRoMap Roadmap identifies five research topics, specifies several key scientific objectives for each topic, and suggests ways to achieve all the objectives. The five AstRoMap Research Topics are • Research Topic 1: Origin and Evolution of Planetary Systems • Research Topic 2: Origins of Organic Compounds in Space • Research Topic 3: Rock-Water-Carbon Interactions, Organic Synthesis on Earth, and Steps to Life • Research Topic 4: Life and Habitability • Research Topic 5: Biosignatures as Facilitating Life Detection It is strongly recommended that steps be taken towards the definition and implementation of a European Astrobiology Platform (or Institute) to streamline and optimize the scientific return by using a coordinated infrastructure and funding system.

  19. AstRoMap European Astrobiology Roadmap

    PubMed Central

    Horneck, Gerda; Westall, Frances; Grenfell, John Lee; Martin, William F.; Gomez, Felipe; Leuko, Stefan; Lee, Natuschka; Onofri, Silvano; Tsiganis, Kleomenis; Saladino, Raffaele; Pilat-Lohinger, Elke; Palomba, Ernesto; Harrison, Jesse; Rull, Fernando; Muller, Christian; Strazzulla, Giovanni; Brucato, John R.; Rettberg, Petra; Capria, Maria Teresa

    2016-01-01

    Abstract The European AstRoMap project (supported by the European Commission Seventh Framework Programme) surveyed the state of the art of astrobiology in Europe and beyond and produced the first European roadmap for astrobiology research. In the context of this roadmap, astrobiology is understood as the study of the origin, evolution, and distribution of life in the context of cosmic evolution; this includes habitability in the Solar System and beyond. The AstRoMap Roadmap identifies five research topics, specifies several key scientific objectives for each topic, and suggests ways to achieve all the objectives. The five AstRoMap Research Topics are • Research Topic 1: Origin and Evolution of Planetary Systems• Research Topic 2: Origins of Organic Compounds in Space• Research Topic 3: Rock-Water-Carbon Interactions, Organic Synthesis on Earth, and Steps to Life• Research Topic 4: Life and Habitability• Research Topic 5: Biosignatures as Facilitating Life Detection It is strongly recommended that steps be taken towards the definition and implementation of a European Astrobiology Platform (or Institute) to streamline and optimize the scientific return by using a coordinated infrastructure and funding system. Key Words: Astrobiology roadmap—Europe—Origin and evolution of life—Habitability—Life detection—Life in extreme environments. Astrobiology 16, 201–243. PMID:27003862

  20. Treatment and Prevention of Breast Cancer Using Multifunctional Inhibitors of Cholesterol Biosynthesis

    DTIC Science & Technology

    2013-06-01

    biosynthetic enzyme oxidosqualene cyclase block proliferation and survival of breast cancer cells. 103rd Annual American Association of Cancer...arrest related protein p21 in breast cancer cells 24 T47-D Cont. RO-5 RO-10 RO-25  Actin Bcl-2 Fig 5B: Inhibition of breast cancer...biosynthetic pathway; these inhibitors are however associated with certain undesirable side effects that limit their use for cancer therapy. Our goal

  1. Anti-ENA profiles related with anti-SS-A/Ro. The detection of Ro52 and Ro60 according to the presence of SS-B/La, and ANA pattern and titer.

    PubMed

    González, D Almeida; Rodríguez, C Casañas; Armas, L Magdalena; Varela, A Roces; Rodríguez, I Marcelino; Duarte, M Troche; de León, A Cabrera

    2014-09-01

    Anti-Ro52 (Ro52) and anti-Ro60 (Ro60) antibodies are associated with different clinical entities. We investigated their relationship with the presence of anti-SS-B/La (SSB) antibody, the pattern and titer of antinuclear antibody (ANA), and the variations in antibody profiles related with anti-SS-A/Ro (SSA) positivity. Our aim was to develop a strategy to increase the efficiency of anti-extractable nuclear antigen (ENA) determinations. Statistical analyses were based on the Chi-squared test for categorical variables, the Mann-Whitney U test to compare profiles, and the odds ratio (OR) and 95% confidence interval (95% CI) to estimate the risk of variability. We analyzed 800 SSA-positive samples with Ro52 or Ro60 reactivity. The most frequent profiles were Ro52+Ro60+SSB (n=349, 43.6%); Ro52+Ro60 (n=126, 15.8%); Ro52 (n=121, 15.1%) and Ro60 (n=71, 8.9%). In samples positive only for SSA and an ANA titer ≤1:640, the most likely profile was positivity for either Ro52 or Ro60, whereas when the ANA titer was >1:640, positivity for both Ro52 and Ro60 simultaneously was more likely (p<0.001). In samples positive for both SSA and SSB, the most likely profile was Ro52+Ro60+SSB regardless of the ANA titer (p=0.001). When only SSA was positive and the ANA staining pattern was nucleolar, centromeric or cytoplasmic, Ro52 positivity was most likely (p<0.001). When both SSA and SSB were positive, both Ro52 and Ro60 were likely to be positive regardless of the ANA staining pattern. In 28.7% of the patients the profile was variable. Variability was significantly greater in those with the SSA profile (23/67) than with the SSA+SSB profile (15/105; OR=1.9, 95% CI=1.1-3.3; p=0.025), and the difference in variability was greatest between the Ro52+Ro60 profile (8/23) and the Ro52+Ro60+SSB profile (8/68; OR=4.2, 95% CI=1.9-9.5; p<0.001). We conclude that to increase efficiency in the immunology laboratory, positivity for Ro52 and Ro60 individually or simultaneously can be deduced from SSB

  2. An Introduction to the RoLI[TM

    ERIC Educational Resources Information Center

    Meyer, Jan H. F.

    2004-01-01

    The Reflections on Learning Inventory (RoLI) is an instrument designed to capture variation in students' engagement of learning--typically in a given disciplinary context or topic-specific 'episode'. Although the RoLI has been employed as a research instrument in a number of published studies on the modelling of student learning in higher…

  3. RoMPS concept review automatic control of space robot

    NASA Technical Reports Server (NTRS)

    1991-01-01

    The Robot operated Material Processing in Space (RoMPS) experiment is being performed to explore the marriage of two emerging space commercialization technologies: materials processing in microgravity and robotics. This concept review presents engineering drawings and limited technical descriptions of the RoMPS programs' electrical and software systems.

  4. 29 CFR 1918.86 - Roll-on roll-off (Ro-Ro) operations (see also § 1918.2, Ro-Ro operations, and § 1918.25).

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... their cargo capacities and shall not be overloaded. (h) Cargo weights. Cargo to be handled via a Ro-Ro ramp shall be plainly marked with its weight in pounds (kilograms). Alternatively, the cargo stow plan or equivalent record containing the actual gross weight of the load may be used to determine...

  5. 29 CFR 1918.86 - Roll-on roll-off (Ro-Ro) operations (see also § 1918.2, Ro-Ro operations, and § 1918.25).

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... their cargo capacities and shall not be overloaded. (h) Cargo weights. Cargo to be handled via a Ro-Ro ramp shall be plainly marked with its weight in pounds (kilograms). Alternatively, the cargo stow plan or equivalent record containing the actual gross weight of the load may be used to determine...

  6. Recent standardization activities on radio on fiber (RoF)

    NASA Astrophysics Data System (ADS)

    Ogawa, Hiroyo; Kuri, Toshiaki; Kanno, Atsushi; Kawanishi, Tetsuya

    2013-12-01

    The Radio on Fiber (RoF) technologies are unique transmission means of radio analog signals through optical fiber cables. These technologies are currently discussed at international standard organizations such as ITU-T, IEC, APT and IEEE802. This invited paper summarizes RoF standardization activities at those standard organizations.

  7. SyRoTek--Distance Teaching of Mobile Robotics

    ERIC Educational Resources Information Center

    Kulich, M.; Chudoba, J.; Kosnar, K.; Krajnik, T.; Faigl, J.; Preucil, L.

    2013-01-01

    E-learning is a modern and effective approach for training in various areas and at different levels of education. This paper gives an overview of SyRoTek, an e-learning platform for mobile robotics, artificial intelligence, control engineering, and related domains. SyRoTek provides remote access to a set of fully autonomous mobile robots placed in…

  8. 9 years of existence of the site astronomy.ro

    NASA Astrophysics Data System (ADS)

    Haus, Marian

    2013-06-01

    The article represents a history of the Astronomical site: http://www.astronomy.ro and its forum http://www.astronomy.ro/forum/. To the actual moment about 1700 members - amateur astronomers from every where in Romania and outside - contribute to this site and forum. The main areas of interst are: Astronomical Instruments, Astrophotography, Eclipses, Solar Astronomy, Comets, Asteroids and Meteors, Optics.

  9. 29 CFR 1918.86 - Roll-on roll-off (Ro-Ro) operations (see also § 1918.2, Ro-Ro operations, and § 1918.25).

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ..., Ro-Ro operations, and § 1918.25). 9 (a) Traffic control system. An organized system of vehicular and pedestrian traffic control shall be established and maintained at each entrance/exit ramp and on ramps within... their cargo capacities and shall not be overloaded. (h) Cargo weights. Cargo to be handled via a...

  10. 29 CFR 1918.86 - Roll-on roll-off (Ro-Ro) operations (see also § 1918.2, Ro-Ro operations, and § 1918.25).

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ..., Ro-Ro operations, and § 1918.25). 9 (a) Traffic control system. An organized system of vehicular and pedestrian traffic control shall be established and maintained at each entrance/exit ramp and on ramps within... their cargo capacities and shall not be overloaded. (h) Cargo weights. Cargo to be handled via a...

  11. Cesáro partial sums of concave univalent functions

    NASA Astrophysics Data System (ADS)

    Aldawish, Ibtisam; Darus, Maslina

    2014-06-01

    In this article, we consider the Cesáro partial sums of certain concave univalent functions. We studied geometric properties of the Cesáro partial sums of certain concave univalent functions in the open unit disk. Examples are illustrated.

  12. Highlights on Novel Technologies for the Detection of Antibodies to Ro60, Ro52, and SS-B

    PubMed Central

    Infantino, M.; Bentow, C.; Seaman, A.; Benucci, M.; Atzeni, F.; Sarzi-Puttini, P.; Olivito, B.; Meacci, F.; Manfredi, M.; Mahler, M.

    2013-01-01

    Objective. We aimed to compare a chemiluminescent immunoassay (CIA, QUANTA Flash) on BIO-FLASH with a multiplex flow immunoassay (MFI) on BioPlex 2200 for the detection of antibodies to Ro60, Ro52, and SS-B. Methods. The study included 241 samples, from patients suffering from systemic autoimmune diseases (n = 108) as well as disease controls (n = 133). All samples were tested for anti-Ro52, anti-Ro60, and anti-SS-B (La) antibodies on QUANTA Flash (INOVA Diagnostics, San Diego, USA) and BioPlex 2200 (Bio-Rad Laboratories Inc., Hercules, USA). Discrepant samples were tested by two independent methods: BlueDot/ANA and QUANTRIX Microarray (both D-tek, Belgium). Results. The overall qualitative agreements were 95.4% (95% confidence interval, CI 92.0–97.7%) for anti-Ro52, 98.8% (95% CI 96.4–99.7%) for anti-Ro60, and 91.7% (95% CI 87.5–94.9%) for anti-SS-B antibodies. There were 34 discrepant samples among all assays (20 anti-SS-B, 11 anti-Ro52, 3 anti-Ro60). 30/33 of retested samples (by D-tek dot blot) agreed with the QUANTA Flash results. Similar findings were obtained with QUANTRIX Microarray kit. Conclusion. QUANTA Flash and BioPlex 2200 show good qualitative agreement. The clinical performances were similar for anti-Ro52 and anti-Ro60 autoantibodies while differences were observed for anti-SS-B (La) antibodies. PMID:24376466

  13. Correction to Clark and Ro (2014).

    PubMed

    2015-01-01

    Reports an error in "Three-pronged assessment and diagnosis of personality disorder and its consequences: Personality functioning, pathological traits, and psychosocial disability" by Lee Anna Clark and Eunyoe Ro (Personality Disorders: Theory, Research, and Treatment, 2014[Jan], Vol 5[1], 55-69). There was an error in the results. Under the subheading, Personality Traits-Functioning Relations, on page 63, the second, third, and fourth paragraph have been revised. The revisions are included in the erratum. (The following abstract of the original article appeared in record 2014-07188-003.) The alternative dimensional model of personality disorder (PD) in the Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5; American Psychiatric Association, 2013), Section III, has two main criteria: impairment in personality functioning and one or more pathological personality traits. The former is defined as disturbances in self-functioning (viz., identity, self-direction), and/or interpersonal functioning (viz., empathy, intimacy). Distinguishing personality functioning and traits is important conceptually, because simply having extreme traits is not necessarily pathological. However, adding personality functioning to PD diagnosis represents an empirical challenge, because the constructs overlap conceptually. Further, there is debate regarding whether diagnosis of mental disorder requires either distress or disability, concepts that also overlap with maladaptive-range personality traits and personality dysfunction. We investigated interrelations among these constructs using multiple self-report measures of each domain in a mixed community-patient sample (N = 402). We examined the structures of functioning (psychosocial disability and personality) and personality traits, first independently, then jointly. The disability/functioning measures yielded the 3 dimensions we have found previously (Ro & Clark, 2013). Trait measures had a hierarchical structure

  14. Assuring the Legacy of the CoRoT Planets

    NASA Astrophysics Data System (ADS)

    Deeg, H. J.; Klagyivik, P.; Alonso, R.; Hoyer, S.

    2015-09-01

    For the long-lasting impact of CoRoT's planet findings, precise knowledge of the times of their transits is of vital importance for any future observing campaigns. Here we give the motivation and first results of a systematic revisit of the transits of most CoRoT planets to refine their ephemeris. As secondary objectives, more precise planet characterisations, from period or transit shape variations on/and from use of a well-defined passband may be obtained.

  15. VizieR Online Data Catalog: CoRoT/Exoplanet fields with MATISSE (Gazzano+, 2010)

    NASA Astrophysics Data System (ADS)

    Gazzano, J.-C.; de Laverny, P.; Deleuil, M.; Recio-Blanco, A.; Bouchy, F.; Moutou, C.; Bijaoui, A.; Ordenovic, C.; Gandoli, D.; Loeillet, B.

    2010-11-01

    Atomic data modifications from VALD initial request, atmospheric parameters for 1227 CoRoT targets, radial velocity for 1534 CoRoT targets, and Vsini for 1604 CoRoT targets in three CoRoT/Exoplanet fields LRa01, LRc01, and SRc01. The reported uncertainties are only internal errors. (6 data files).

  16. Higher order multi-dimensional extensions of Cesàro theorem

    NASA Astrophysics Data System (ADS)

    Accardi, Luigi; Ji, Un Cig; Saitô, Kimiaki

    2015-12-01

    The Cesàro theorem is extended to the cases: (1) higher order Cesàro mean for sequence (discrete case); and (2) higher order, multi-dimensional and continuous Cesàro mean for functions. Also, we study the Cesàro theorem for the case of positive-order.

  17. Regulation of renal peripheral benzodiazepine receptors by anion transport inhibitors

    SciTech Connect

    Basile, A.S.; Lueddens, W.M.; Skolnick, P.

    1988-01-01

    The in vitro and in vivo regulation of (/sup 3/H)Ro 5-4864 binding to peripheral benzodiazepine receptors (PBR) by ion transport/exchange inhibitors was studied in the kidney. The potencies of 9-anthroic acid, furosemide, bumetanide, hydrochlorothiazide and SITS as inhibitors of (/sup 3/H)Ro 5-4864 binding to renal membranes were consistent with their actions as anion transport inhibitors (Ki approx. = 30 - 130 ..mu..M). In contrast, spironolactone, amiloride, acetazolamide, and ouabain were less potent (Ki=100-1000 ..mu..M). Administration of furosemide to rats for five days resulted in a profound diuresis accompanied by a significant increase in PBR density (43%) that was apparent by the fifth day of treatment. Administration of hydrochlorothiazide or Ro 5-4864 for five days also caused diuresis and increased renal PBR density. Both the diuresis and increased density of PBR produced by Ro 5-4864 were blocked by coadministration of PK 11195, which alone had no effect on either PBR density or urine volume. The equilibrium binding constants of (/sup 3/H)Ro 5-4864 to cardiac membranes were unaffected by administration of any of these drugs. These findings suggest that renal PBR may be selectively modulated in vivo and in vitro by administration of ion transport/exchange inhibitors. 36 references, 4 tables.

  18. The selective 5-HT6 receptor antagonist Ro4368554 restores memory performance in cholinergic and serotonergic models of memory deficiency in the rat.

    PubMed

    Lieben, Cindy K J; Blokland, Arjan; Sik, Ayhan; Sung, Eric; van Nieuwenhuizen, Petra; Schreiber, Rudy

    2005-12-01

    Antagonists at serotonin type 6 (5-HT(6)) receptors show activity in models of learning and memory. Although the underlying mechanism(s) are not well understood, these effects may involve an increase in acetylcholine (ACh) levels. The present study sought to characterize the cognitive-enhancing effects of the 5-HT(6) antagonist Ro4368554 (3-benzenesulfonyl-7-(4-methyl-piperazin-1-yl)1H-indole) in a rat object recognition task employing a cholinergic (scopolamine pretreatment) and a serotonergic- (tryptophan (TRP) depletion) deficient model, and compared its pattern of action with that of the acetylcholinesterase inhibitor metrifonate. Initial testing in a time-dependent forgetting task employing a 24-h delay between training and testing showed that metrifonate improved object recognition (at 10 and 30 mg/kg, p.o.), whereas Ro4368554 was inactive. Both, Ro4368554 (3 and 10 mg/kg, intraperitoneally (i.p.)) and metrifonate (10 mg/kg, p.o., respectively) reversed memory deficits induced by scopolamine and TRP depletion (10 mg/kg, i.p., and 3 mg/kg, p.o., respectively). In conclusion, although Ro4368554 did not improve a time-related retention deficit, it reversed a cholinergic and a serotonergic memory deficit, suggesting that both mechanisms may be involved in the facilitation of object memory by Ro4368554 and, possibly, other 5-HT(6) receptor antagonists.

  19. CoRoT: Harvest of the exoplanet program

    NASA Astrophysics Data System (ADS)

    Moutou, Claire; Deleuil, Magali; Guillot, Tristan; Baglin, Annie; Bordé, Pascal; Bouchy, Francois; Cabrera, Juan; Csizmadia, Szilárd; Deeg, Hans J.

    2013-11-01

    One of the objectives of the CoRoT mission is the search for transiting extrasolar planets using high-precision photometry, and the accurate characterization of their fundamental parameters. The CoRoT satellite consecutively observes crowded stellar fields since February 2007, in high-cadence precise photometry; periodic eclipses are detected and analyzed in the stellar light curves. Then complementary observations using ground-based facilities allows establishing the nature of the transiting body and its mass. CoRoT has acquired more than 163,000 light curves and detected about 500 planet candidates. A fraction of them (5%) are confirmed planets whose masses are independently measured. Main highlights of the CoRoT discoveries are: (i) the variety of internal structures in close-in giant planets, (ii) the characterization of the first known transiting rocky planet, CoRoT-7b, and (iii) multiple constraints on the formation, evolution, role of tides in planetary systems.

  20. Evaluation of RO modules for the SSP ETC/LSS.

    NASA Technical Reports Server (NTRS)

    Jasionowski, W. J.; Bambenek, R. A.

    1973-01-01

    During the past eight years the NASA Manned Spacecraft Center has supported the development of an Integrated Water and Waste Management System for use in the Space Station Prototype (SSP) Environmental Thermal Control/Life-Support System (ETC/LSS). This system includes the reverse osmosis (RO) process for recycling wash water and the compression distillation process for recovering useable water from urine, urinal flush water, humidity condensate, commode flush water and the wash water concentrated by RO. This paper summarizes the experimental work performed during the past four years to select the best commercially available RO module for this system and to also define which surfactants and germicides are most compatible with the selected module.

  1. Asteroseismology of OB stars with CoRoT

    NASA Astrophysics Data System (ADS)

    Degroote, P.; Aerts, C.; Samadi, R.; Miglio, A.; Briquet, M.; Auvergne, M.; Baglin, A.; Baudin, F.; Catala, C.; Michel, E.

    2010-12-01

    The CoRoT satellite is revolutionizing the photometric study of massive O-type and B-type stars. During its long runs, CoRoT observed the entire main sequence B star domain, from typical hot β Cep stars, via cooler hybrid p- and g-mode pulsators to the SPB stars near the edge of the instability strip. CoRoT lowers the sensitivity barrier from the typical mmag-precision reached from the ground, to the μmag-level reached from space. Within the wealth of detected and identified pulsation modes, relations have been found in the form of multiplets, combination of frequencies, and frequency- and period spacings. This wealth of observational evidence is finally providing strong constraints to test current models of the internal structure and pulsations of hot stars. Aside from the expected opacity driven modes with infinite lifetime, other unexpected types of variability are detected in massive stars, such as modes of stochastic nature. The simultaneous observation of all these light curve characteristics implies a challenge for both observational asteroseismology and stellar modelling. The CoRoT space mission was developed and is operated by the French space agency CNES, with participation of ESA's RSSD and Science Programmes, Austria, Belgium, Brazil, Germany, and Spain.

  2. StRoBe: A Classroom-on-Task Measure.

    ERIC Educational Resources Information Center

    Marchant, Gregory J.

    Researchers as well as others evaluating teachers or programs are often interested in the verbal and non-verbal behaviors related to the learning of students in classrooms. The Student Record of Behavior (StRoBe) is a classroom observation instrument designed to provide simple low inference information concerning student behaviors related to…

  3. Removing Arsenic with a Softening/RO Combo

    EPA Science Inventory

    This paper provides a very short summary of the arsenic demonstration program and the limited test results from the point-of-use (POU), reverse osmosis (RO) project in Homedale, ID. Preformance data is presented on the effectiveness of the POU treatment system to remove arseni...

  4. AmeriFlux US-Ro1 Rosemount- G21

    DOE Data Explorer

    Baker, John [USDA-ARS; Griffis, Tim [University of Minnesota; Griffis, Timothy [University of Minnesota

    2016-01-01

    This is the AmeriFlux version of the carbon flux data for the site US-Ro1 Rosemount- G21. Site Description - This tower is located in a farm field farmed in accordance with the dominant farming practice in the region: a corn/soybean rotation with chisel plow tillage in the fall following corn harvest and in the spring following soybeans.

  5. AmeriFlux US-Ro3 Rosemount- G19

    DOE Data Explorer

    Baker, John [USDA-ARS; Griffis, Tim [University of Minnesota

    2016-01-01

    This is the AmeriFlux version of the carbon flux data for the site US-Ro3 Rosemount- G19. Site Description - This tower is located in a farm field farmed in accordance with the cominant farming practice in the region: a corn/soybean rotation with chisel plow tillage in the fall following corn harvest and in the spring following soybeans.

  6. Isotretinoin (Ro-Accutane) teratogenesis. A case report.

    PubMed

    Giannoulis, C H; Papathanasiou, K; Tantanasis, T H; Vaitsi, V; Tzafettas, I

    2005-01-01

    A case of teratogenesis in a 16-year-old pregnant patient is described. She had been using 60 mg Ro-Accutane daily till the 16th week of gestation. Sonography showed no cephalic skull up to the frontal bone of the fetus. A central lagostroma was also detected.

  7. Empirical Error Analysis of GPS RO Atmospheric Profiles

    NASA Astrophysics Data System (ADS)

    Scherllin-Pirscher, B.; Steiner, A. K.; Foelsche, U.; Kirchengast, G.; Kuo, Y.

    2010-12-01

    In the upper troposphere and lower stratosphere (UTLS) region the radio occultation (RO) technique provides accurate profiles of atmospheric parameters. These profiles can be used in operational meteorology (i.e., numerical weather prediction), atmospheric and climate research. We present results of an empirical error analysis of GPS RO data retrieved at UCAR and at WEGC and compare data characteristics of CHAMP, GRACE-A, and Formosat-3/COSMIC. Retrieved atmospheric profiles of bending angle, refractivity, dry pressure, dry geopotential height, and dry temperature are compared to reference profiles extracted from ECMWF analysis fields. This statistical error characterization yields a combined (RO observational plus ECMWF model) error. We restrict our analysis to the years 2007 to 2009 due to known ECMWF deficiencies prior to 2007 (e.g., deficiencies in the representation of the austral polar vortex or the weak representation of tropopause height variability). The GPS RO observational error is determined by subtracting the estimated ECMWF error from the combined error in terms of variances. Our results indicate that the estimated ECMWF error and the GPS RO observational error are approximately of the same order of magnitude. Differences between different satellites are small below 35 km. The GPS RO observational error features latitudinal and seasonal variations, which are most pronounced at stratospheric altitudes at high latitudes. We present simplified models for the observational error, which depend on a few parameters only (Steiner and Kirchengast, JGR 110, D15307, 2005). These global error models are derived from fitting simple analytical functions to the GPS RO observational error. From the lower troposphere up to the tropopause, the model error decreases closely proportional to an inverse height law. Within a core "tropopause region" of the upper troposphere/lower stratosphere the model error is constant and above this region it increases exponentially with

  8. Cesàro operators on Hardy spaces in the unit ball

    NASA Astrophysics Data System (ADS)

    Guo, Xiaoqin; Ren, Guangbin

    2008-03-01

    This article establishes the boundedness of the generalized Cesàro operator on holomorphic Hardy spaces in the unit ball. The approach consists in writing the generalized Cesàro operator as a composition of certain integral operators.

  9. Comparison of antibody assays for detection of autoantibodies to Ro 52, Ro 60 and La associated with primary Sjögren's syndrome.

    PubMed

    Trier, Nicole Hartwig; Nielsen, Inger Ødum; Friis, Tina; Houen, Gunnar; Theander, Elke

    2016-06-01

    Anti-Ro(52/60) and anti-La constitute the hallmark autoantibodies in primary Sjögren's syndrome, being present in 40-70% of sera. Several anti-Ro/La assays exist, but antibody detection appears to be assay-specific, thus the aim of this study was to compare several anti-Ro/La assays. In total, 96 sera from individuals with primary Sjögren's syndrome and 114 healthy controls were tested for anti-Ro 52/60 and anti-La in 17 immunoassays. Especially the immunoassays used for detection of anti-Ro 52 differed in their sensitivity (48-79%), while only small differences in sensitivities were observed for the anti-Ro 60 (69-77%) anti-La (39-44%) assays. Concordances of 65%, 79% and 73% for the anti-Ro 52, anti-Ro 60 and anti-La assays were found, respectively. The majority of the assays yielded high specificities, primarily ranging from 97 to 100%, except from a single anti-Ro 60 assay, which yielded a specificity of 79%. Occasionally, reactivity levels were increased in a few assays, indicating that false-positive results can be obtained when applying assays of reduced specificity. In general, the commercial assays appeared to perform better than the in-house analyses. When correcting the in-house assays for background reactivity, sensitivities were reduced by approximately 7%, 17%, and 19% for anti-Ro 52, anti-Ro 60 and anti-La assays, respectively, illustrating the pitfalls when applying immunoassays for detection of autoantibodies, which in theory may apply to commercial assays as well. Finally, increased total sensitivities were obtained when combining assays. These studies contribute to clarify the clinical utility of immunoassays for detection of autoantibodies of Ro 52, Ro 60 and La and illustrate that the most efficient strategy to maximize antibody sensitivity is to combine several assays.

  10. Gene encoding human Ro-associated autoantigen Y5 RNA.

    PubMed Central

    Maraia, R; Sakulich, A L; Brinkmann, E; Green, E D

    1996-01-01

    Ro ribonucleoproteins are composed of Y RNAs and the Ro 60 kDa protein. While the Ro 60 kDa protein is implicated in an RNA discard pathway that recognizes 3'-extended 5S rRNAs, the function of Y RNAs remains unknown [O'Brien,C.A. and Wolin,S.L. (1995) Genes Dev. 8,2891-2903]. Y5 RNA occupies a large fraction of Ro 60 kDa protein in human Ro RNPs, contains an atypical 3'-extension not found on other Y RNAs, and constitutes an RNA antigen in certain autoimmune patients [Boulanger et al. (1995) Clin. Exp. Immunol. 99, 29-36]. An overabundance of Y RNA retroposed pseudogenes has previously complicated the isolation of mammalian Y RNA genes. The source gene for Y5 RNA was isolated from human DNA as well as from Galago senegalis DNA. Authenticity of the hY5 RNA gene was demonstrated in vivo and its activity was compared with the hY4 RNA gene that also uses a type 3 promoter for RNA polymerase III. The hY5 RNA gene was subsequently found to reside within a few hundred thousand base pairs of other Y RNA genes and the linear order of the four human Y RNA genes on chromosome 7q36 was determined. Phylogenetic comparative analyses of promoter and RNA structure indicate that the Y5 RNA gene has been subjected to positive selection during primate evolution. Consistent with the proposal of O'Brien and Harley [O'Brian,C.A. and Wolin,S.L. (1992) Gene 116, 285-289], analysis of flanking sequences suggest that the hY5 RNA gene may have originated as a retroposon. PMID:8836182

  11. Red clover coumarate 3'-hydroxylase (CYP98A44) is capable of hydroxylating p-coumaroyl-shikimate but not p-coumaroyl-malate: implications for the biosynthesis of phaselic acid.

    PubMed

    Sullivan, Michael L; Zarnowski, Robert

    2010-01-01

    Red clover (Trifolium pratense) leaves accumulate several mumol of phaselic acid [2-O-caffeoyl-L-malate] per gram fresh weight. Post-harvest oxidation of such o-diphenols to o-quinones by endogenous polyphenol oxidases (PPO) prevents breakdown of forage protein during storage. Forages like alfalfa (Medicago sativa) lack both foliar PPO activity and o-diphenols. Consequently, breakdown of their protein upon harvest and storage results in economic losses and release of excess nitrogen into the environment. Understanding how red clover synthesizes o-diphenols such as phaselic acid will help in the development of forages utilizing this natural system of protein protection. We have proposed biosynthetic pathways in red clover for phaselic acid that involve a specific hydroxycinnamoyl-CoA:malate hydroxycinnamoyl transferase. It is unclear whether the transfer reaction to malate to form phaselic acid involves caffeic acid or p-coumaric acid and subsequent hydroxylation of the resulting p-coumaroyl-malate. The latter would require a coumarate 3'-hydroxylase (C3'H) capable of hydroxylating p-coumaroyl-malate, an activity not previously described. Here, a cytochrome P450 C3'H (CYP98A44) was identified and its gene cloned from red clover. CYP98A44 shares 96 and 79% amino acid identity with Medicago truncatula and Arabidopsis thaliana C3'H proteins that are capable of hydroxylating p-coumaroyl-shikimate and have been implicated in monolignol biosynthesis. CYP98A44 mRNA is expressed in stems and flowers and to a lesser extent in leaves. Immune serum raised against CYP98A44 recognizes a membrane-associated protein in red clover stems and leaves and cross-reacts with C3'H proteins from other species. CYP98A44 expressed in Saccharomyces cerevisiae is capable of hydroxylating p-coumaroyl-shikimate, but not p-coumaroyl-malate. This finding indicates that in red clover, phaselic acid is likely formed by transfer of a caffeoyl moiety to malic acid, although the existence of a second C

  12. Stellar classification of CoRoT targets

    NASA Astrophysics Data System (ADS)

    Damiani, C.; Meunier, J.-C.; Moutou, C.; Deleuil, M.; Ysard, N.; Baudin, F.; Deeg, H.

    2016-11-01

    Context. The CoRoT mission was the first dedicated to the search for exoplanets from space. The CoRoT exoplanet channel observed about 163 600 targets to detect transiting planetary companions. In addition to the search for exoplanets, the extremely precise photometric time series provided by CoRoT for this vast number of stars is an invaluable resource for stellar studies. Because CoRoT targets are faint (11 ≤ r ≤ 16) and close to the galactic plane, only a small subsample has been observed spectroscopically. Consequently, the stellar classification of CoRoT targets required the design of a classification method suited for the needs and time frame of the mission. Aims: We describe the latest classification scheme used to derive the spectral type of CoRoT targets, which is based on broadband multi-colour photometry. We assess the accuracy of this spectral classification for the first time. Methods: We validated the method on simulated data. This allows the quantification of the effect of different sources of uncertainty on the spectral type. Using galaxy population synthesis models, we produced a synthetic catalogue that has the same properties as the CoRoT targets. In this way, we are able to predict typical errors depending on the estimated luminosity class and spectral type. We also compared our results with independent estimates of the spectral type. Cross-checking those results allows us to identify the systematics of the method and to characterise the stellar populations observed by CoRoT. Results: We find that the classification method performs better for stars that were observed during the mission-dedicated photometric ground-based campaigns.The luminosity class is wrong for less than 7% of the targets. Generally, the effective temperature of stars classified as early type (O, B, and A) is overestimated. Conversely, the temperature of stars classified as later type tends to be underestimated. This is mainly due to the adverse effect of interstellar

  13. THE MASS OF CoRoT-7b

    SciTech Connect

    Hatzes, Artie P.; Wuchterl, Guenther; Fridlund, Malcolm; Gandolfi, Davide; Nachmani, Gil; Mazeh, Tsevi; Valencia, Diana; Hebrard, Guillaume; Borde, Pascal; Carone, Ludmila; Paetzold, Martin; Udry, Stephane; Bouchy, Francois; Deleuil, Magali; Moutou, Claire; Barge, Pierre; Deeg, Hans; Tingley, Brandon; Dvorak, Rudolf; Ferraz-Mello, Sylvio E-mail: malcolm.fridlund@esa.int; and others

    2011-12-10

    The mass of CoRoT-7b, the first transiting super-Earth exoplanet, is still a subject of debate. A wide range of masses have been reported in the literature ranging from as high as 8 M{sub Circled-Plus} to as low as 2.3 M{sub Circled-Plus }. This range in mass is largely due to the activity level of the star that contributes a significant amount of radial velocity (RV) 'jitter' and how the various methods correct this jitter. Although most mass determinations give a density consistent with a rocky planet, the lower value permits a bulk composition that can be up to 50% water. We present an analysis of the CoRoT-7b RV measurements that uses very few and simple assumptions in treating the activity signal. By analyzing those RV data for which multiple measurements were made in a given night, we remove the activity related RV contribution without any a priori model. We argue that the contribution of activity to the final RV curve is negligible and that the K-amplitude due to the planet is well constrained. This yields a mass of 7.42 {+-} 1.21 M{sub Circled-Plus} and a mean density of {rho} = 10.4 {+-} 1.8 gm cm{sup -3}. CoRoT-7b is similar in mass and radius to the second rocky planet to be discovered, Kepler-10b, and within the errors they have identical bulk densities-they are virtual twins. These bulk densities lie close to the density-radius relationship for terrestrial planets similar to what is seen for Mercury. CoRoT-7b and Kepler-10b may have an internal structure more like Mercury than the Earth.

  14. Climate Change detection using GPS RO and CMIP5 data

    NASA Astrophysics Data System (ADS)

    Molodtsov, S.; Kirilenko, A.; Olsen, D.

    2013-12-01

    General circulation models' (GCMs) response to the increase of atmospheric concentration of greenhouse gases (GHG) due to anthropogenic emissions is evident under variety of forcing scenarios. However the investigation of the anthropogenic signal in the real climate system is challenging as it requires long term high accuracy global coverage data. GPS Radio Occultation (GPS RO) technique becomes close to meeting all of these requirements, becoming the benchmark for climate data. We implemented the analysis for upper troposphere - lower stratosphere (UTLS) region between 50°N and 50°S latitudes, where the GPS RO data has higher quality. For observations, we used vertical profiles of temperature and/or geopotential heights from 2001-2008 CHAMP and 2006-2011 COSMIC occultation. GCM trends of the response patterns to the external forcings of respective climate variables were extracted from CMIP 5 GCM runs under representative concentration pathways (RCP) 8.5 and historical climate scenarios, for the same period. Natural variability was calculated using CMIP 5 GCM runs under preindustrial control scenario. The GPS RO data was downloaded from CDAAC website, GCM CMIP 5 data was obtained from Earth System Grid web page. We used optimal fingerprinting method which is generalized multivariate regression adjusted for climate change detection studies. Optimal fingerprinting allows estimating of the climate signal separately from natural climate variability. Following this methodology we applied Empirical Orthogonal Functions to filter observed and modeled data in order to decrease impact of natural variability and maximize the signal to noise ratio. Temperature and geopotential height trends in the simulated and observed climate datasets show similar features of warming of the upper troposphere and cooling of the lower stratosphere in the tropics region. Using optimal fingerprinting we found that the anthropogenic signal emerges from natural variability in GPS RO temperature

  15. On the geometric properties of Cesàro spaces

    NASA Astrophysics Data System (ADS)

    Astashkin, Sergey V.

    2012-04-01

    It is proved that the Cesàro space \\operatorname{Ces}_{p} \\lbrack 0,1 \\rbrack , 1\\le p<\\infty, contains a complemented subspace isomorphic to l^q if and only if either q=1 or q=p. A class of subspaces of this space that contain complemented copies of the space l^p is distinguished. Bibliography: 16 titles.

  16. High performance RO membranes for desalination and wastewater reclamation and their operation results.

    PubMed

    Henmi, M; Fusaoka, Y; Tomioka, H; Kurihara, M

    2010-01-01

    Reverse osmosis (RO) membrane is one of the most powerful tools for solving the global water crisis, and is used in a variety of water treatment scenes such as drinking water purification, waste-water treatment, boiler feed water production, ultra pure water production for semiconductor industry, etc. The desired performance of RO membrane varies according to quality of feed water being treated, and Toray has been developing RO membranes with suitable characteristic for each operating condition. RO membranes for seawater desalination and wastewater reclamation are especially regarded as most promising targets. Recently, high boron removal and energy saving RO membrane for seawater desalination and low fouling RO membrane for wastewater reclamation have been developed. In this paper, the prospect of attaining these renovative RO membrane, and furthermore, job references will be discussed.

  17. Sensitization by SR-2508 plus Ro 03-8799

    SciTech Connect

    Stone, H.B.; Luu, Y.H.; Lam, K.N.

    1986-07-01

    The primary toxicity of Ro 03-8799 is a central nervous system toxicity, whereas that of SR-2508 is a peripheral neuropathy. The feasibility of reducing overall toxicity while maintaining maximal radiosensitization by using the two sensitizers together was tested. The LD50/2 of Ro 03-8799 was 0.68 mg/g body wt (mg/gbw) after intravenous (i.v.) administration, and that of SR-2508 was 4.4 mg/gbw after i.v. administration. When both drugs were given together in equitoxic proportions, the LD50/2 was 0.45 mg of Ro 03-8799 plus 2.9 mg of SR-2508/gbw. These doses are 66% of the respective LD50/2 values of the drugs when given separately. Radiosensitization was evaluated using in vivo-in vitro assays with EMT6/SF tumors in BALB/c mice. At drug doses between 10 and 60% of the LD50/2, sensitization was generally maximal and similar to that from misonidazole, but there was less sensitization below this dose, both with the drugs given separately and together. If chronic toxicities of these drugs overlap as do the acute toxicities there will be little or no additional benefit from using these drugs in combination, compared to using them separately.

  18. Down-regulation of p-coumaroyl quinate/shikimate 3'-hydroxylase (C3'H) and cinnamate 4-hydroxylase (C4H) genes in the lignin biosynthetic pathway of Eucalyptus urophylla x E. grandis leads to improved sugar release

    SciTech Connect

    Sykes, Robert W.; Gjersing, Erica L.; Foutz, Kirk; Rottmann, William H.; Kuhn, Sean A.; Foster, Cliff E.; Ziebell, Angela; Turner, Geoffrey B.; Decker, Stephen R.; Hinchee, Maud A. W.; Davis, Mark F.

    2015-08-27

    In this study, lignocellulosic materials provide an attractive replacement for food-based crops used to produce ethanol. Understanding the interactions within the cell wall is vital to overcome the highly recalcitrant nature of biomass. One factor imparting plant cell wall recalcitrance is lignin, which can be manipulated by making changes in the lignin biosynthetic pathway. In this study, eucalyptus down-regulated in expression of cinnamate 4-hydroxylase (C4H, EC 1.14.13.11) or p-coumaroyl quinate/shikimate 3'-hydroxylase (C3'H, EC 1.14.13.36) were evaluated for cell wall composition and reduced recalcitrance.

  19. Staurosporine, but not Ro 31-8220, induces interleukin 2 production and synergizes with interleukin 1alpha in EL4 thymoma cells.

    PubMed Central

    Mahon, T M; Matthews, J S; O'Neill, L A

    1997-01-01

    Protein kinase C (PKC) has been implicated in interleukin 1 (IL1) signal transduction in a number of cellular systems, either as a key event in IL1 action or as a negative regulator. Here we have examined the effects of two PKC inhibitors, staurosporine and the more selective agent Ro 31-8220, on IL1 responses in the murine thymoma line EL4.NOB-1. A 1 h pulse of staurosporine was found to strongly potentiate the induction of IL2 by IL1alpha in these cells. In contrast, neither a pulse nor prolonged incubation with Ro 31-8220 affected the response to IL1alpha. Both agents blocked the response to PMA, however. A 1 h pulse of staurosporine was also found to induce IL2 production on its own, activate the transcription factor nuclear factor kappaB (NFkappaB) and increase the expression of a NFkappaB-linked reporter gene. It synergized with IL1alpha in all of these responses. Ro 31-8220 was again without effect, although both staurosporine and Ro 31-8220 blocked the activation of NFkappaB by PMA. Finally, staurosporine caused the translocation of PKC-alpha and -epsilon, and to a lesser extent PKC-beta, but not PKC-θ or -zeta, from the cytosol to the membrane, although a similar effect was observed with Ro 31-8220. The results suggest that PKC is not involved in IL1alpha signalling in EL4 cells. Furthermore, the potentiating effect of staurosporine on IL1alpha action does not involve PKC inhibition, and is likely to be at the level of NFkappaB activation. PMID:9224627

  20. Altered dopamine D2-like receptor binding in rats with behavioral sensitization to quinpirole: effects of pre-treatment with Ro 41-1049a

    PubMed Central

    Culver, Kirsten E.; Szechtman, Henry; Levant, Beth

    2008-01-01

    Repeated treatment with the dopamine D2/D3 receptor agonist quinpirole produces a sensitized behavioral response in rats manifested as an increase in locomotor activity. Pre-treatment with certain monoamine oxidase inhibitors, such as Ro 41-1049 [N-(2-aminomethyl)-5-(3-fluorophenyl)-4-thiazolecarboxamide HCl], changes the sensitized response from locomotion to stationary, self-directed mouthing. In this study, the effects of quinpirole sensitization, with and without pre-treatment with Ro 41-1049, were determined on dopamine D2-like receptors in the nucleus accumbens and the striatum. Long-Evans rats were pre-treated with Ro 41-1049 (1 mg/kg) 90 min prior to administration of quinpirole (0.5 mg/kg, 8 injections, every 3–4 days). Dopamine D2-like receptor binding was determined 3 days after the last injection by ex vivo radioligand assays using [3H]spiperone and [3H]quinpirole. Densities of [3H]spiperone- and [3H]quinpirole-labeled sites were both increased 32% in the nucleus accumbens of rats with demonstrated locomotor sensitization to quinpirole. In contrast, the density of dopamine D2-like receptors in quinpirole-sensitized rats pre-treated with Ro 41-1049 was not different from saline controls. These findings support the involvement of alterations in dopamine D2-like receptors in the development of locomotor sensitization to quinpirole and suggest that modification of these alterations in dopamine D2-like receptors contributes to the change from sensitized locomotion to mouthing observed when rats are pre-treated with Ro 41-1049. PMID:18644362

  1. The effects of two synthetic glycoprotein IIb/IIIa antagonists, Ro 43-8857 and L-700,462, on platelet aggregation and bleeding in guinea-pigs and dogs: evidence that Ro 43-8857 is orally active.

    PubMed

    Cook, N S; Bruttger, O; Pally, C; Hagenbach, A

    1993-11-15

    In vitro platelet aggregation studies in whole blood were used to define the species-specificity profile of two synthetic GP-IIb/IIIa antagonists, Ro 43-8857 and L-700,462. Aggregation of rhesus monkey platelets was inhibited with a similar potency to human platelets, whereas both compounds were poor antagonists in mini-pig, rabbit or hamster blood. Compared to human platelets, Ro 43-8857 was 2-3-fold less active as an inhibitor of dog and guinea-pig platelet aggregation, whereas L-700,462 was, respectively, 4- and 14-fold less active in these species. In vivo investigations with these two compounds were performed in anesthetized guinea-pigs and conscious dogs, with bleeding times measured on small mesenteric arteries or on the inner jowl respectively. Ex vivo ADP-induced whole blood platelet aggregation was completely inhibited in guinea-pigs by Ro 43-8857 following intravenous administration of 0.1 mg/kg and intraduodenal administration of 3 mg/kg, with a duration of action exceeding 5 hours. Mesenteric bleeding times were prolonged by Ro 43-8857 only at doses causing supra-maximal inhibition of aggregation, suggesting these two effects could be partially dissociated. L-700,462 (3 mg/kg i.v.) was shorter acting than Ro 43-8857 in guinea-pigs (duration approximately 1 hour) and the anti-aggregatory effect was accompanied by mesenteric bleeding time prolongations. In conscious dogs, ex vivo aggregation was inhibited to approximately 80% by Ro 43-8857 (0.3 mg/kg i.v. or 10 mg/kg p.o.) and L-700,462 (1 mg/kg i.v.). However, bleeding time prolongations accompanied these anti-aggregatory effects with both compounds. In conclusion, we have shown clear differences between two synthetic GP-IIb/IIIa antagonists, both in terms of their species-specificity in vitro and in terms of their in vivo profile, and in particular the propensity to promote bleeding from mesenteric arteries in guinea-pigs. However, the ability of Ro 43-8857 to discriminate between anti-aggregatory and

  2. SS-A/Ro52 promotes apoptosis by regulating Bcl-2 production

    SciTech Connect

    Jauharoh, Siti Nur Aisyah; Saegusa, Jun; Sugimoto, Takeshi; Ardianto, Bambang; Kasagi, Shimpei; Sugiyama, Daisuke; Kurimoto, Chiyo; Tokuno, Osamu; Nakamachi, Yuji; Kumagai, Shunichi; Kawano, Seiji

    2012-01-06

    Highlights: Black-Right-Pointing-Pointer Ro52{sup low} HeLa cells are resistant to apoptosis upon various stimulations. Black-Right-Pointing-Pointer Ro52 is upregulated by IFN-{alpha}, etoposide, or IFN-{gamma} and anti-Fas Ab. Black-Right-Pointing-Pointer Ro52-mediated apoptosis is independent of p53. Black-Right-Pointing-Pointer Ro52 selectively regulates Bcl-2 expression. -- Abstract: SS-A/Ro52 (Ro52), an autoantigen in systemic autoimmune diseases such as systemic lupus erythematosus and Sjoegren's syndrome, has E3 ligase activity to ubiquitinate proteins that protect against viral infection. To investigate Ro52's role during stress, we transiently knocked it down in HeLa cells by siRo52 transfection. We found that Ro52{sup low} HeLa cells were significantly more resistant to apoptosis than wild-type HeLa cells when stimulated by H{sub 2}O{sub 2}- or diamide-induced oxidative stress, IFN-{alpha}, IFN-{gamma} and anti-Fas antibody, etoposide, or {gamma}-irradiation. Furthermore, Ro52-mediated apoptosis was not influenced by p53 protein level in HeLa cells. Depleting Ro52 in HeLa cells caused Bcl-2, but not other Bcl-2 family molecules, to be upregulated. Taken together, our data showed that Ro52 is a universal proapoptotic molecule, and that its proapoptotic effect does not depend on p53, but is exerted through negative regulation of the anti-apoptotic protein Bcl-2. These findings shed light on a new physiological role for Ro52 that is important to intracellular immunity.

  3. Dispersion and nonlinear effects in OFDM-RoF system

    NASA Astrophysics Data System (ADS)

    Alhasson, Bader H.; Bloul, Albe M.; Matin, M.

    2010-08-01

    The radio-over-fiber (RoF) network has been a proven technology to be the best candidate for the wireless-access technology, and the orthogonal frequency division multiplexing (OFDM) technique has been established as the core technology in the physical layer of next generation wireless communication system, as a result OFDM-RoF has drawn attentions worldwide and raised many new research topics recently. At the present time, the trend of information industry is towards mobile, wireless, digital and broadband. The next generation network (NGN) has motivated researchers to study higher-speed wider-band multimedia communication to transmit (voice, data, and all sorts of media such as video) at a higher speed. The NGN would offer services that would necessitate broadband networks with bandwidth higher than 2Mbit/s per radio channel. Many new services emerged, such as Internet Protocol TV (IPTV), High Definition TV (HDTV), mobile multimedia and video stream media. Both speed and capacity have been the key objectives in transmission. In the meantime, the demand for transmission bandwidth increased at a very quick pace. The coming of 4G and 5G era will provide faster data transmission and higher bit rate and bandwidth. Taking advantages of both optical communication and wireless communication, OFDM Radio over Fiber (OFDM-RoF) system is characterized by its high speed, large capacity and high spectral efficiency. However, up to the present there are some problems to be solved, such as dispersion and nonlinearity effects. In this paper we will study the dispersion and nonlinearity effects and their elimination in OFDM-radio-over-fiber system.

  4. Potential prodrugs of 6-acetylmethylenepenicillanic acid (Ro 15-1903).

    PubMed

    Adam, S; Then, R; Angehrn, P

    1986-06-01

    The synthesis and biological activities of a series of non-classical penicillins are described. These compounds were synthesized by treating the pivaloyloxymethyl ester of 6-acetylmethylenepenicillanic acid (Ro 15-1903) with various nucleophiles. They were found to be less active against the beta-lactamases from Proteus vulgaris 1028, Escherichia coli 1024, Klebsiella pneumoniae NCTC 418 and E. coli RTEM than the parent compound. Nevertheless, synergy with ampicillin against whole bacterial cells producing beta-lactamases was evident, although the single compounds did not exhibit antibacterial properties. With the compounds 2a and 2b, synergistic interaction with ampicillin could also be demonstrated in mice.

  5. 123I-labeling and evaluation of Ro 43-0463, a SPET tracer for MAO-B imaging.

    PubMed

    Beer, H F; Rossetti, I; Frey, L D; Hasler, P H; Schubiger, P A

    1995-10-01

    Using the copper assisted halogen exchange the MAO-B inhibitor Ro 43-0463, N-(2-aminoethyl)-5-iodo-2-pyridinecarboxamide, was labelled with 123I as well as with 125I to allow in vitro and in vivo investigations including SPET with healthy volunteers. Ro 43-0463 is known to inhibit reversibly and specifically MAO-B, having an IC50 of 3 x 10(-8) Mol/L. The labeling in the presence of CuSO4 and ascorbic acid was optimised, varying time (30 to 105 min), precursor concentration (1-3.5 mg) and temperature (130-200 degrees C). The labeling yield ranged between 60 and 70%. Purification was achieved with Lichrosorb RP-18 (5 micron, 250 x 8 mm) and 1.5 mL/min 0.36 M H3PO4/EtOH 97/3 [0.01 M (NH4)2HPO4]. After neutralisation and sterile filtration the final activity concentration ranged between 18.5 and 37 MBq/mL. Biodistribution studies showed a brain to blood ratio greater than 1 within 1 h p.i. The main radiation burden calculated from these animal data is to alimentary and excretory organs and the ovaries. Autoradiography was performed using rat brain slices and 5 nM [125I]Ro 43-0463 in TRIS-buffer pH 7.4 for 90 min at 20 degrees C. Its radioactivity pattern corresponds to the known distribution of MAO-B in the rat brain. By displacement with L-deprneyl the highly specific binding of R0 43-0463 was proven in vitro. SPECT studies with normal volunteers corresponded with the pattern found in autoradiography.

  6. Gamma-Secretase/Notch Signalling Pathway Inhibitor RO4929097 in Treating Patients With Stage IV Melanoma

    ClinicalTrials.gov

    2016-05-06

    Acral Lentiginous Malignant Melanoma; Lentigo Maligna Malignant Melanoma; Nodular Malignant Melanoma; Recurrent Melanoma; Solar Radiation-related Skin Melanoma; Stage IV Melanoma; Superficial Spreading Malignant Melanoma

  7. Effects of COMT inhibitors on striatal dopamine metabolism: A microdialysis study

    NASA Technical Reports Server (NTRS)

    Kaakkola, S.; Wurtman, R. J.

    1992-01-01

    In vivo microdialysis was used to examine the effect of two new catechol-O-methyltransferase (COMT) inhibitors, Ro 40-7592 and OR-611, on extracellular levels of dopamine, dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), and 5-hydroxyindoleacetic acid (5-HIAA) in rat striatum. The interactions of the COMT inhibitors with nomifensine, clorgyline, and deprenyl were also studied. Ro 40-7592 (3-30 mg/kg. i.p.) decreased dose-dependently the efflux of HVA, increased that of DOPAC, and tended to increase that of dopamine. Higher doses of OR-611 (30-100 mg/kg, i.p.) also decreased the dialysate level of HVA, increased that of DOPAC, and tended to increase that of dopamine. Ro 40-7592 was about ten-fold as potent as OR-611. Neither of the COMT inhibitors changed dialysate levels of 6-HIAA. An OR-611 dose of 10 mg/kg i.p. had no significant effect, in contrast to Ro 40-7592, on any of the parameters studied; this dose was thus used to differentiate between the effects of central and peripheral COMT inhibition. Both nomifensine (15 mg/kg, i.p.) and clorgyline (4 mg/kg, i.p.) alone elevated extracellular dopamine levels, and lowered those of DOPAC and HVA, though there were quantitative and temporal differences between the drugs. L-deprenyl (1 mg/kg, i.p.) alone had no significant effect on any of the compounds measured. Ro 40-7592 (10 mg/kg, i.p.) potentiated the effect of nomifensine on dopamine efflux, and it tended to increase clorgyline-induced dopamine efflux. DOPAC levels in dialysates were significantly increased by combinations of Ro 40-7592 and nomifensine or clorgyline, whereas HVA remained about as low as they were after Ro 40-7592 alone. Ro 40-7592 had no significant interactions with L-deprenyl. OR-611 (10 mg/kg, i.p.) did not modify the effects on dopamine metabolism of nomifensine, clorgyline, or L-deprenyl. These data show that Ro 40-7592 is a potent centrally active COMT inhibitor, whereas OR-611 is principally a peripherally active inhibitor

  8. Conversion of tunneled hemodialysis catheter into HeRO device can provide immediate access for hemodialysis.

    PubMed

    Vasquez, Julio C; DeLaRosa, Jacob; Rahim, Fahim; Rahim, Naeem

    2010-11-01

    Patients with central venous occlusion who are ''tunneled catheter dependent'' are a challenge for hemodialysis access. A relatively new option for them is the hemodialysis reliable outflow (HeRO) device that can be totally implanted subcutaneously. However, patients still require a tunneled hemodialysis catheter that is used until the HeRO device is mature, 4 to 6 weeks later. Here, we describe a conversion of an existing tunneled hemodialysis catheter into a HeRO device, which was combined with a ''self-sealing'' Flixene graft. This allowed almost immediate use of the HeRO device without the need for placement of a catheter.

  9. Removal of organic contaminants by RO and NF membranes

    NASA Technical Reports Server (NTRS)

    Yoon, Yeomin; Lueptow, Richard M.

    2005-01-01

    Rejection characteristics of organic and inorganic compounds were examined for six reverse osmosis (RO) membranes and two nanofiltration (NF) membranes that are commercially available. A batch stirred-cell was employed to determine the membrane flux and the solute rejection for solutions at various concentrations and different pH conditions. The results show that for ionic solutes the degree of separation is influenced mainly by electrostatic exclusion, while for organic solutes the removal depends mainly upon the solute radius and molecular structure. In order to provide a better understanding of rejection mechanisms for the RO and NF membranes, the ratio of solute radius (r(i,s)) to effective membrane pore radius (r(p)) was employed to compare rejections. An empirical relation for the dependence of the rejection of organic compounds on the ratio r(i,s)/r(p) is presented. The rejection for organic compounds is over 75% when r(i,s)/r(p) is greater than 0.8. In addition, the rejection of organic compounds is examined using the extended Nernst-Planck equation coupled with a steric hindrance model. The transport of organic solutes is controlled mainly by diffusion for the compounds that have a high r(i,s)/r(p) ratio, while convection is dominant for compounds that have a small r(i,s)/r(p) ratio. c2005 Elsevier B.V. All rights reserved.

  10. Novel, potent and selective inhibitors of protein kinase C show oral anti-inflammatory activity.

    PubMed

    Nixon, J S; Bishop, J; Bradshaw, D; Davis, P D; Hill, C H; Elliott, L H; Kumar, H; Lawton, G; Lewis, E J; Mulqueen, M

    1991-01-01

    Clarification of the precise role of protein kinase C (PKC) in cellular functional responses has been hampered by a lack of potent, selective inhibitors. The structural lead provided by staurosporine, a potent but non-selective protein kinase (PK) inhibitor, was used to derive a series of bis(indolyl)maleimides of which the most potent, Ro 31-8425 (I50: PKC = 8 nM) showed 350-fold selectivity for PKC over cAMP-dependent protein kinase. Ro 31-8425 antagonised cellular processes triggered by phorbol esters (potent, specific PKC activators) and inhibited the allogeneic mixed lymphocyte reaction, suggesting a role for PKC in T-cell activation. Methylation of the primary amine in Ro 31-8425 produced an analogue. Ro 31-8830 which, when administered orally, produced a dose-dependent inhibition of a phorbol ester-induced paw oedema in mice (minimum effective dose = 15 mg/kg). Ro 31-8830 also selectively inhibited the secondary inflammation in a developing adjuvant arthritis model in the rat. The results presented here suggest that these selective inhibitors of PKC may have therapeutic value in the treatment of T-cell-mediated autoimmune diseases.

  11. Gas-Phase Ozonolysis of Cycloalkenes: Formation of Highly Oxidized RO2 Radicals and Their Reactions with NO, NO2, SO2, and Other RO2 Radicals.

    PubMed

    Berndt, Torsten; Richters, Stefanie; Kaethner, Ralf; Voigtländer, Jens; Stratmann, Frank; Sipilä, Mikko; Kulmala, Markku; Herrmann, Hartmut

    2015-10-15

    The gas-phase reaction of ozone with C5-C8 cycloalkenes has been investigated in a free-jet flow system at atmospheric pressure and a temperature of 297 ± 1 K. Highly oxidized RO2 radicals bearing at least 5 O atoms in the molecule and their subsequent reaction products were detected in most cases by means of nitrate-CI-APi-TOF mass spectrometry. Starting from a Criegee intermediate after splitting-off an OH-radical, the formation of these RO2 radicals can be explained via an autoxidation mechanism, meaning RO2 isomerization (ROO → QOOH) and subsequently O2 addition (QOOH + O2 → R'OO). Time-dependent RO2 radical measurements concerning the ozonolysis of cyclohexene indicate rate coefficients of the intramolecular H-shifts, ROO → QOOH, higher than 1 s(-1). The total molar yield of highly oxidized products (predominantly RO2 radicals) from C5-C8 cycloalkenes in air is 4.8-6.0% affected with a calibration uncertainty by a factor of about two. For the most abundant RO2 radical from cyclohexene ozonolysis, O,O-C6H7(OOH)2O2 ("O,O" stands for two O atoms arising from the ozone attack), the determination of the rate coefficients of the reaction with NO2, NO, and SO2 yielded (1.6 ± 0.5) × 10(-12), (3.4 ± 0.9) × 10(-11), and <10(-14) cm(3) molecule(-1) s(-1), respectively. The reaction of highly oxidized RO2 radicals with other peroxy radicals (R'O2) leads to detectable accretion products, RO2 + R'O2 → ROOR' + O2, which allows to acquire information on peroxy radicals not directly measurable with the nitrate ionization technique applied here. Additional experiments using acetate as the charger ion confirm conclusively the existence of highly oxidized RO2 radicals and closed-shell products. Other reaction products, detectable with this ionization technique, give a deeper insight in the reaction mechanism of cyclohexene ozonolysis.

  12. In vitro activity of RO363, a beta1-adrenoceptor selective agonist.

    PubMed Central

    Iakovidis, D.; Malta, E.; McPherson, G. A.; Raper, C.

    1980-01-01

    1 The beta-adrenoceptor stimulant effects of RO363 and (--)-isoprenaline have been compared in a variety of isolated tissue preparations. 2 RO363 is approximately half as potent as (--)-isoprenaline in tissues where actions are due to beta1-receptor activation (guinea-pig atrial and ileal preparations and ventricular strips from the rabbit, rat and guinea-pig. 3 In uterine and lung strip preparations from the guinea-pig, where responses are due to beta2-receptor stimulation. RO363 is 100 to 350 times less active than (--)-isoprenaline and has a low intrinsic activity. 4 In spontaneously contracted tracheal preparations from the guinea-pig, RO363 is a full agonist and is approximately half as potent as (--)-isoprenaline. These effects of RO363 are due to the activation of a population of beta1-receptors in the tissue since RO363 and (--)-isoprenaline have the same relative potencies in trachea, cardiac and ileal preparations. In addition the Kb values for practolol are similar in all these preparations when RO363 is used as the agonist. 5 The results show that RO363 is a potent and highly selective beta1-receptor agonist. PMID:6103722

  13. Emerging roles for the Ro 60 kDa autoantigen in noncoding RNA metabolism

    PubMed Central

    Sim, Soyeong; Wolin, Sandra L.

    2011-01-01

    All cells contain an enormous variety of ribonucleoprotein complexes that function in diverse processes. Although the mechanisms by which many of these RNPs contribute to cell metabolism are well understood, the roles of others are only now beginning to be revealed. A member of this latter category, the Ro 60 kDa protein and its associated noncoding Y RNAs, was discovered because the protein component is a frequent target of the autoimmune response in patients with the rheumatic diseases systemic lupus erythematosus and Sjögren’s syndrome. Recent studies have shown that Ro is ring-shaped, binds the single-stranded ends of misfolded noncoding RNAs in its central cavity, and may function in noncoding RNA quality control. Although Ro is not present in yeast, many bacterial genomes contain potential Ro orthologs. In the radiation-resistant eubacterium Deinococcus radiodurans, the Ro ortholog functions with exoribonucleases during stress-induced changes in RNA metabolism. Moreover, in both D. radiodurans and animal cells, Ro is involved in the response to multiple types of environmental stress. Finally, Y RNAs can influence the subcellular location of Ro, inhibit access of the central cavity to other RNAs and may also act as binding sites for proteins that influence Ro function. PMID:21823229

  14. TU-CD-BRD-00: Incident Learning / RO-ILS

    SciTech Connect

    2015-06-15

    It has long been standard practice in radiation oncology to report internally when a patient’s treatment has not gone as planned and to report events to regulatory agencies when legally required. Most potential errors are caught early and never affect the patient. Quality assurance steps routinely prevent errors from reaching the patient, and these “near misses” are much more frequent than treatment errors. A growing number of radiation oncology facilities have implemented incident learning systems to report and analyze both errors and near misses. Using the term “incident learning” instead of “event reporting” emphasizes the need to use these experiences to change the practice and make future errors less likely and promote an educational, non-punitive environment. There are challenges in making such a system practical and effective. Speakers from institutions of different sizes and practice environments will share their experiences on how to make such a system work and what benefits their clinics have accrued. Questions that will be addressed include: How to create a system that is easy for front line staff to access How to motivate staff to report How to promote the system as positive and educational and not punitive or demeaning How to organize the team for reviewing and responding to reports How to prioritize which reports to discuss in depth How not to dismiss the rest How to identify underlying causes How to design corrective actions and implement change How to develop useful statistics and analysis tools How to coordinate a departmental system with a larger risk management system How to do this without a dedicated quality manager Some speakers’ experience is with in-house systems and some will share experience with the AAPM/ASTRO national Radiation Oncology Incident Learning System (RO-ILS). Reports intended to be of value nationally need to be comprehensible to outsiders; examples of useful reports will be shown. There will be ample time set

  15. High Flux, Fouling Resistant Membranes for RO Pretreatment

    DTIC Science & Technology

    2010-07-30

    hollow-fiber, ultrafiltration membrane. Activities in the second 3 months of the project included: 1. completing the set up of production and lab...develop a fouling resistant, hollow‐fiber,  ultrafiltration  membrane.  Activities in the second 3 months of the project included:  1. completing the set up...of the RO.  However, current commercial  ultrafiltration  and microfiltration  membranes used for RO pre‐treatment are inadequate and subject to fouling

  16. Bisindolylmaleimide protein-kinase-C inhibitors delay the decline in DNA synthesis in mouse hair follicle organ cultures.

    PubMed

    Harmon, C S; Nevins, T D; Ducote, J; Lutz, D

    1997-01-01

    We have used a series of bisindolylmaleimide selective protein-kinase C (PKC) inhibitors to investigate the role of this enzyme in the regulation of cell proliferation in mouse hair follicle organ cultures. Mouse whisker follicles were isolated by microdissection, and rates of DNA synthesis during culture were determined from 3H-thymidine incorporation. The bisindolylmaleimides Ro 31-7549, Ro 31-8161, Ro 31-8425 and Ro 31-8830 inhibit isolated brain PKC with IC50 values of 8-80 nM, are > 60-fold less potent against protein kinase A, and inhibit PKC-mediated protein phosphorylation in platelets with IC50 values in the range 0.25-4.4 microM. These PKC inhibitors were found to increase levels of mouse hair follicle DNA synthesis, with EC50 values in the range 1-4 microM and maximal levels in the range 151-197% of control. Ro 31-7549 had an IC50 value 50-fold lower than that of minoxidil, while the maximal level of DNA synthesis for the PKC inhibitor was 86% higher. Incubation of mouse hair follicles with Ro 31-7549 resulted in a delay of approximately 24 h in the onset of decline in follicular DNA synthesis rates. Ro 31-6045 and Ro 31-7208, bisindolylmaleimides without activity in the platelet PKC assay, did not affect mouse hair follicle DNA synthesis rates. Taken together, these findings show that PKC mediates, at least in part, the rapid loss of proliferative activity that occurs in mouse whisker follicles in culture, and provide further evidence that PKC plays a role as a negative proliferative signal in hair follicles.

  17. VizieR Online Data Catalog: CoRoT observation log (N2-4.4) (CoRoT 2016)

    NASA Astrophysics Data System (ADS)

    COROT Team

    2014-03-01

    CoRoT, a space astronomy mission, has measured photometric micro-variability of stars from minutes to months (up to 150 days) with a high duty cycle (more than 90%). The mission was led by CNES in association with four French laboratories and 7 participating countries and agencies (Austria, Belgium, Brazil, Germany, Spain, and the ESA Science Programme). The satellite was composed of a PROTEUS platform (the 3rd in the series) and a unique instrument: a stellar rapid photometer. It was launched on December 27th 2006 by a Soyuz Rocket, from Bakonour. The mission has lasted almost 6 years (the nominal 3-year duration and a 3-year extension) and has observed more than 160 000 stars. It stopped sending data on November 2nd 2012. Two regions of the sky were accessible for long period of time: circles of 10 degrees centered on the equator around alpha=06:50 and alpha=18:50. They were called the CoRoT eyes: the "anticenter" and the "center eye" (as they are approximately in these directions). Each pointing covers 1.4x2.8 square degrees within one of those CoRoT eyes. The original scientific objectives were focussed on the study of stellar pulsations (asteroseismology) to probe the internal structure of stars, and the detection of small exoplanets through their "transiting in front of their host star, and the measurement of their size. This lead to introduce two modes of observations, working simultaneously: - The "bright star" mode dedicated to very precise seismology of a small sample of bright and closeby stars - The "faint star" mode, observing a very large number of stars at the same time, to detect transits, which are rare events, as they imply the alignment of the star, the planet and the observer. The large amount of data gathered in this mode turned out to be extremely fruitful for many topics of stellar physics. Beyond these two initial objectives, CoRoT data revealed stellar variability associated with various other phenomena: granulation, rotational modulation

  18. Rapid field assessment of RO desalination of brackish agricultural drainage water.

    PubMed

    Thompson, John; Rahardianto, Anditya; Gu, Han; Uchymiak, Michal; Bartman, Alex; Hedrick, Marcos; Lara, David; Cooper, Jim; Faria, Jose; Christofides, Panagiotis D; Cohen, Yoram

    2013-05-15

    Rapid field evaluation of RO feed filtration requirements, selection of effective antiscalant type and dose, and estimation of suitable scale-free RO recovery level were demonstrated using a novel approach based on direct observation of mineral scaling and flux decline measurements, utilizing an automated Membrane Monitor (MeMo). The MeMo, operated in a stand-alone single-pass desalting mode, enabled rapid assessment of the adequacy of feed filtration by enabling direct observation of particulate deposition on the membrane surface. The diagnostic field study with RO feed water of high mineral scaling propensity revealed (via direct MeMo observation) that suspended particulates (even for feed water of turbidity <1 NTU) could serve as seeds for promoting surface crystal nucleation. With feed filtration optimized, a suitable maximum RO water recovery, with complete mineral scale suppression facilitated by an effective antiscalant dose, can be systematically and directly identified (via MeMo) in the field for a given feed water quality. Scale-free operating conditions, determined via standalone MeMo rapid diagnostic tests, were shown to be applicable to spiral-would RO system as validated via both flux decline measurements and ex-situ RO plant membrane scale monitoring. It was shown that the present approach is suitable for rapid field assessment of RO operability and it is particularly advantageous when evaluating water sources of composition that may vary both temporally and across the regions of interest.

  19. WARM SPITZER PHOTOMETRY OF THE TRANSITING EXOPLANETS CoRoT-1 AND CoRoT-2 AT SECONDARY ECLIPSE

    SciTech Connect

    Deming, Drake; Knutson, Heather; Agol, Eric; Cowan, Nicolas B.; Desert, Jean-Michel; Charbonneau, David; Burrows, Adam; Fortney, Jonathan J.; Laughlin, Gregory; Langton, Jonathan; Showman, Adam P.; Lewis, Nikole K.

    2011-01-10

    We measure secondary eclipses of the hot giant exoplanets CoRoT-1 at 3.6 and 4.5 {mu}m, and CoRoT-2 at 3.6 {mu}m, both using Warm Spitzer. We find that the Warm Spitzer mission is working very well for exoplanet science. For consistency of our analysis we also re-analyze archival cryogenic Spitzer data for secondary eclipses of CoRoT-2 at 4.5 and 8 {mu}m. We compare the total data for both planets, including optical eclipse measurements by the CoRoT mission, and ground-based eclipse measurements at 2 {mu}m, to existing models. Both planets exhibit stronger eclipses at 4.5 than at 3.6 {mu}m, which is often indicative of an atmospheric temperature inversion. The spectrum of CoRoT-1 is best reproduced by a 2460 K blackbody, due either to a high altitude layer that strongly absorbs stellar irradiance, or an isothermal region in the planetary atmosphere. The spectrum of CoRoT-2 is unusual because the 8 {mu}m contrast is anomalously low. Non-inverted atmospheres could potentially produce the CoRoT-2 spectrum if the planet exhibits line emission from CO at 4.5 {mu}m, caused by tidal-induced mass loss. However, the viability of that hypothesis is questionable because the emitting region cannot be more than about 30% larger than the planet's transit radius, based on the ingress and egress times at eclipse. An alternative possibility to account for the spectrum of CoRoT-2 is an additional opacity source that acts strongly at wavelengths less than 5 {mu}m, heating the upper atmosphere while allowing the deeper atmosphere seen at 8 {mu}m to remain cooler. We obtain a similar result as Gillon et al. for the phase of the secondary eclipse of CoRoT-2, implying an eccentric orbit with e cos({omega}) = -0.0030 {+-} 0.0004.

  20. Cross-resistance analysis of human immunodeficiency virus type 1 variants individually selected for resistance to five different protease inhibitors.

    PubMed Central

    Tisdale, M; Myers, R E; Maschera, B; Parry, N R; Oliver, N M; Blair, E D

    1995-01-01

    Human immunodeficiency virus type 1 (HIV-1) protease inhibitor-resistant variants, isolated on passage of HIV-1HXB2 in MT-4 cells with five different protease inhibitors, have been examined for cross-resistance to five inhibitors. The protease inhibitors studied were Ro 31-8959, A-77003, XM323, L-735,524, and VX-478. Resistant variants with two to four mutations within their protease sequence and 9- to 40-fold-decreased susceptibility were selected for all five inhibitors within six to eight passes in cell culture. Passage of a zidovudine-resistant mutant in Ro 31-8959 generated a dual reverse transcriptase- and protease-resistant virus. Variants were cloned directly into a modified pHXB2-D infectious clone for cross-resistance analysis. Although the resistant variants selected possessed different combinations of protease mutations for each inhibitor, many showed cross-resistance to the other inhibitors, and one showed cross-resistance to all five inhibitors. Interestingly, some mutants showed increased susceptibility to some inhibitors. Further HIV passage studies in the combined presence of two protease inhibitors demonstrated that in vitro it was possible to delay significantly selection of mutations producing resistance to one or both inhibitors. These studies indicate that there may be some rationale for combining different protease inhibitors as well as protease and reverse transcriptase inhibitors in HIV combination therapy. PMID:7486905

  1. Ceftriaxone (Ro 13-9904) therapy of serious infection.

    PubMed Central

    Bradsher, R W

    1982-01-01

    Ceftriaxone (Ro 13-9904), a newly developed cephalosporin with a long half-life, was evaluated for efficacy and safety in 19 patients with serious infections. Underlying illnesses were present in 16 patients. Ceftriaxone was given intravenously every 12 h. Infections treated included gram-negative bacillary pneumonias (two cases), staphylococcal and streptococcal soft tissue-skeletal infections (six cases), spontaneous peritonitis (two cases), and complicated urinary tract infections (nine cases). Bacteremia was present in three patients. Microbiological and clinical cures were achieved in all but one case, although three patients with urinary infection had recurrences 6 weeks posttherapy. The only failure occurred in a patient with pneumonia who had a Pseudomonas aeruginosa isolated from sputum with an initial minimal inhibitory concentration of 4 micrograms/ml, but after 9 days of therapy, a repeat isolate had a minimal inhibitory concentration of 32 micrograms/ml. The minimal inhibitory concentrations for the other isolates ranged from less than or equal to 0.6 to 8.0 micrograms/ml. The mean peak plasma level of ceftriaxone was 99.9 micrograms/ml. The only side effects noted were drug fever in one patient, phlebitis in two patients, and thrombocytosis in four patients. PMID:6289739

  2. Physico-chemical and in-silico analysis of a phytocystatin purified from Brassica juncea cultivar RoAgro 5444.

    PubMed

    Khan, Shumaila; Ahmad, Sabahuddin; Siddiqi, Mohammad Imran; Bano, Bilqees

    2016-12-01

    This study describes the isolation and purification of a phytocystatin from seeds of Brassica juncea (Indian mustard; cultivar RoAgro 5444), which is an important oilseed crop both agriculturally and economically. The protein was purified by gel filtration chromatography with 24.3% yield and 204-fold purification, and visualised by 2D gel electrophoresis. The 18.1 kDa mustard cystatin was highly specific for cysteine proteinases. The plant cystatin inhibited cathepsin B, confirming its role in conferring pest resistance. The inhibitor was highly stable over a pH range of 3-10 and retained significant inhibitory potential up to 70 °C. The stoichiometry of its interaction with papain, determined by isothermal calorimetry, suggests a 1:1 complex. Secondary structural elements calculated by far-UV circular dichroism (CD) spectroscopy show an 18.8% α-helical and 21% β-sheet structure. The protein was a non-competitive inhibitor of thiol proteinases. The Stokes radius and frictional co-efficient were used to describe the shape and size of the protein. Homology modelling and docking studies proposed a prototype illustrating the Brassica phytocystatin mediated papain inhibition. Molecular dynamics (MD) study revealed the excellent stability of the papain-phytocystatin complex during a simulation for 100 ns. Detailed results identify the mustard cystatin as an important member of the phytocystatin family.

  3. Transiting exoplanets from the CoRoT space mission. VII. The ``hot-Jupiter''-type planet CoRoT-5b

    NASA Astrophysics Data System (ADS)

    Rauer, H.; Queloz, D.; Csizmadia, Sz.; Deleuil, M.; Alonso, R.; Aigrain, S.; Almenara, J. M.; Auvergne, M.; Baglin, A.; Barge, P.; Bordé, P.; Bouchy, F.; Bruntt, H.; Cabrera, J.; Carone, L.; Carpano, S.; de La Reza, R.; Deeg, H. J.; Dvorak, R.; Erikson, A.; Fridlund, M.; Gandolfi, D.; Gillon, M.; Guillot, T.; Guenther, E.; Hatzes, A.; Hébrard, G.; Kabath, P.; Jorda, L.; Lammer, H.; Léger, A.; Llebaria, A.; Magain, P.; Mazeh, T.; Moutou, C.; Ollivier, M.; Pätzold, M.; Pont, F.; Rabus, M.; Renner, S.; Rouan, D.; Shporer, A.; Samuel, B.; Schneider, J.; Triaud, A. H. M. J.; Wuchterl, G.

    2009-10-01

    Aims: The CoRoT space mission continues to photometrically monitor about 12 000 stars in its field-of-view for a series of target fields to search for transiting extrasolar planets ever since 2007. Deep transit signals can be detected quickly in the “alarm-mode” in parallel to the ongoing target field monitoring. CoRoT's first planets have been detected in this mode. Methods: The CoRoT raw lightcurves are filtered for orbital residuals, outliers, and low-frequency stellar signals. The phase folded lightcurve is used to fit the transit signal and derive the main planetary parameters. Radial velocity follow-up observations were initiated to secure the detection and to derive the planet mass. Results: We report the detection of CoRoT-5b, detected during observations of the LRa01 field, the first long-duration field in the galactic anti-center direction. CoRoT-5b is a “hot Jupiter-type” planet with a radius of 1.388+0.046-0.047 R_Jup, a mass of 0.467+0.047-0.024 M_Jup, and therefore, a mean density of 0.217+0.031-0.025 g cm-3. The planet orbits an F9V star of 14.0 mag in 4.0378962 ± 0.0000019 days at an orbital distance of 0.04947+0.00026-0.00029 AU. Observations made with SOPHIE spectrograph at the Observatoire de Haute Provence (07B.PNP.MOUT), France, and HARPS spectrograph at ESO La Silla Observatory (072.C-0488(E), 082.C-0312(A)), and partly based on observations made at the Anglo-Australian Telescope. The CoRoT space mission, launched on December 27, 2006, was developed and is operated by CNES, with the contribution of Austria, Belgium, Brasil, ESA, Germany, and Spain.

  4. Roll-On/Roll-Off (RO/RO) Discharge Facility Tests with MV CYGNUS and SS ATLANTIC BEAR (COTS CNO Project 299, DT-IIF-1).

    DTIC Science & Technology

    1983-11-01

    AD-R139 346 ROLL-ON/ROLL-OFF (RO/RO) DISCHARGE FACILITY TESTS NITH 1/1 MY CYGNUS AND SS A..(U) DAVID N TAYLOR NAVAL SHIP RESEARCH AND DEVELOPMENT...MICROCOPY RESOLUTION TEST CHART NATIONA. DUEAU OF STANOAD$S-1963-A •-’ ,jh DAVID W. TAYLOR NAVAL SHIP RMSEARCH AND DEVELOPMENT CENTER ROLL-ON/ROLL...by the David W. Taylor Naval Ship Research and Development Center (DTNSRDC), Mobile Support Systems Office, Code 1190, Task Area Y0816.002 and Work

  5. Transiting exoplanets from the CoRoT space mission. XXV. CoRoT-27b: a massive and dense planet on a short-period orbit

    NASA Astrophysics Data System (ADS)

    Parviainen, H.; Gandolfi, D.; Deleuil, M.; Moutou, C.; Deeg, H. J.; Ferraz-Mello, S.; Samuel, B.; Csizmadia, Sz.; Pasternacki, T.; Wuchterl, G.; Havel, M.; Fridlund, M.; Angus, R.; Tingley, B.; Grziwa, S.; Korth, J.; Aigrain, S.; Almenara, J. M.; Alonso, R.; Baglin, A.; Barros, S. C. C.; Bordé, P.; Bouchy, F.; Cabrera, J.; Díaz, R. F.; Dvorak, R.; Erikson, A.; Guillot, T.; Hatzes, A.; Hébrard, G.; Mazeh, T.; Montagnier, G.; Ofir, A.; Ollivier, M.; Pätzold, M.; Rauer, H.; Rouan, D.; Santerne, A.; Schneider, J.

    2014-02-01

    Aims: We report the discovery of a massive and dense transiting planet CoRoT-27b on a 3.58-day orbit around a 4.2 Gyr-old G2 star. The planet candidate was identified from the CoRoT photometry, and was confirmed as a planet with ground-based spectroscopy. Methods: The confirmation of the planet candidate is based on radial velocity observations combined with imaging to rule out blends. The characterisation of the planet and its host star was carried out using a Bayesian approach where all the data (CoRoT photometry, radial velocities, and spectroscopic characterisation of the star) are used jointly. The Bayesian analysis included a study whether the assumption of white normally distributed noise holds for the CoRoT photometry and whether the use of a non-normal noise distribution offers advantages in parameter estimation and model selection. Results: CoRoT-27b has a mass of 10.39 ± 0.55MJup, a radius of 1.01 ± 0.04RJup, a mean density of 12.6-1.67+1.92g cm-3, and an effective temperature of 1500 ± 130 K. The planet orbits around its host star, a 4.2 Gyr-old G2-star with a mass M⋆ = 1.06M⊙ and a radius R⋆ = 1.05R⊙, on a 0.048 ± 0.007 AU orbit of 3.58 days. The radial velocity observations allow us to exclude highly eccentric orbits, namely, e < 0.065 with 99% confidence. Given its high mass and density, theoretical modelling of CoRoT-27b is demanding. We identify two solutions with heavy element mass fractions of 0.11 ± 0.08M⊕ and 0.07 ± 0.06M⊕, but even solutions void of heavy elements cannot be excluded. We carry out a secondary eclipse search from the CoRoT photometry using a method based on Bayesian model selection, but conclude that the noise level is too high to detect eclipses shallower than 9% of the transit depth. Using a non-normal noise model was shown not to affect the parameter estimation results, but led to significant improvement in the sensitivity of the model selection process. The CoRoT space mission, launched on December 27, 2006

  6. Quality of life in functional rhinoplasty: rhinoplasty outcomes evaluation German version (ROE-D).

    PubMed

    Bulut, Olcay Cem; Plinkert, Peter K; Wallner, Frank; Baumann, Ingo

    2016-09-01

    The aim of this study was to validate a German version of the rhinoplasty outcomes evaluation (ROE) questionnaire. A prospective study was conducted and a German translated ROE (ROE-D) questionnaire administered to 100 patients preoperatively, 6 and 12 months postoperatively. The translation was performed according to internationally accepted guidelines. To validate this instrument, we evaluated its reliability, validity and sensitivity. ROE-D was completed by 54 patients after 6 months and by 69 patients 1 year after functional rhinoplasty. Cronbach's α indicated good internal consistency. Reliability was tested with a split-half-reliability, showing significant correlation. Discrimination validity was demonstrated by a comparison with healthy controls. Sensitivity to change showed medium to large effects. ROE-D is a reliable, validated and sensitive German instrument for measuring health-related quality of life in patients after rhinoplasty. The ROE-D focuses mainly on the aesthetic aspects of the rhinoplasty surgery.

  7. A Novel Endonuclease Inhibitor Exhibits Broad-Spectrum Anti-Influenza Virus Activity In Vitro

    PubMed Central

    Jones, Jeremy C.; Marathe, Bindumadhav M.; Lerner, Christian; Kreis, Lukas; Gasser, Rodolfo; Pascua, Philippe Noriel Q.; Najera, Isabel

    2016-01-01

    Antiviral drugs are important in preventing and controlling influenza, particularly when vaccines are ineffective or unavailable. A single class of antiviral drugs, the neuraminidase inhibitors (NAIs), is recommended for treating influenza. The limited therapeutic options and the potential risk of antiviral resistance are driving the search for additional small-molecule inhibitors that act on influenza virus proteins. The acid polymerase (PA) of influenza viruses is a promising target for new antivirals because of its essential role in initiating virus transcription. Here, we characterized a novel compound, RO-7, identified as a putative PA endonuclease inhibitor. RO-7 was effective when added before the cessation of genome replication, reduced polymerase activity in cell-free systems, and decreased relative amounts of viral mRNA and genomic RNA during influenza virus infection. RO-7 specifically inhibited the ability of the PA endonuclease domain to cleave a nucleic acid substrate. RO-7 also inhibited influenza A viruses (seasonal and 2009 pandemic H1N1 and seasonal H3N2) and B viruses (Yamagata and Victoria lineages), zoonotic viruses (H5N1, H7N9, and H9N2), and NAI-resistant variants in plaque reduction, yield reduction, and cell viability assays in Madin-Darby canine kidney (MDCK) cells with nanomolar to submicromolar 50% effective concentrations (EC50s), low toxicity, and favorable selective indices. RO-7 also inhibited influenza virus replication in primary normal human bronchial epithelial cells. Overall, RO-7 exhibits broad-spectrum activity against influenza A and B viruses in multiple in vitro assays, supporting its further characterization and development as a potential antiviral agent for treating influenza. PMID:27381402

  8. Clinical significance of antibodies to Ro52/TRIM21 in systemic sclerosis

    PubMed Central

    2012-01-01

    Introduction Autoantibodies to Ro52 recently identified as TRIM21 are among the most common autoantibodies in systemic autoimmune rheumatic diseases, but their clinical association remains poorly understood. We undertook this study to determine the clinical and serologic associations of anti-Ro52/TRIM21 antibodies in patients with systemic sclerosis (SSc). Methods Detailed clinical data and sera from 963 patients with SSc enrolled in a multicenter cohort study were collected and entered into a central database. Antibodies to Ro52/TRIM21 and other autoantibodies were detected with an addressable laser-bead immunoassay and different enzyme-linked immunosorbent assay (ELISA) systems. Associations between anti-Ro52/TRIM21 antibodies and clinical and other serologic manifestations of SSc were investigated. Results Anti-Ro52/TRIM21 antibodies were present in 20% of SSc patients and overlapped with other main SSc-related antibodies, including anti-centromere (by immunofluorescence and centromere protein (CENP)-A and CENP-B ELISA), anti-topoisomerase I, anti-RNA polymerase III, and anti-Pm/Scl antibodies. Anti-Ro52/TRIM21 antibodies were strongly associated with interstitial lung disease (odds ratio (OR), 1.53; 95% confidence interval (CI), 1.11 to 2.12; P = 0.0091) and overlap syndrome (OR, 2.06; 95% CI, 1.01 to 4.19; P = 0.0059). Conclusions Anti-Ro52/TRIM21 antibodies were the second most common autoantibodies in this SSc cohort. In SSc, anti-Ro52/TRIM21 antibodies may be a marker of interstitial lung disease and overlap syndrome. PMID:22394602

  9. Percutaneous endovascular management of occluded HeRO dialysis access device.

    PubMed

    Vasquez, Julio C; DeLaRosa, Jacob; Leon, Juan J; Rahim, Naeem; Rahim, Fahim

    2010-01-01

    The Hemodialysis Reliable Outflow (HeRO) device is a novel alternative for dialysis access in patients with no suitable veins in the upper extremities. We placed a HeRO device in a 67-year-old woman with end-stage renal disease and 2 months later, it was being used for hemodialysis. After 1 month of uneventful use, the device thrombosed and it was rescued with a percutaneous endovascular approach. The device remains patent 6 months after the intervention.

  10. The influence of antiscalants on biofouling of RO membranes in seawater desalination.

    PubMed

    Sweity, Amer; Oren, Yoram; Ronen, Zeev; Herzberg, Moshe

    2013-06-15

    Antiscalants are surface active polyelectrolyte compounds commonly used in reverse osmosis (RO) desalination processes to avoid membrane scaling. In spite of the significant roles of antiscalants in preventing membrane scaling, they are prone to enhance biofilm growth on RO membranes by either altering membrane surface properties or by serving as nutritional source for microorganisms. In this study, the contribution of antiscalants to membrane biofouling in seawater desalination was investigated. The effects of two commonly used antiscalants, polyphosphonate- and polyacrylate-based, were tested. The effects of RO membrane (DOW-Filmtec SW30 HRLE-400) exposure to antiscalants on its physico-chemical properties were studied, including the consequent effects on initial deposition and growth of the sessile microorganisms on the RO membrane surface. The effects of antiscalants on membrane physico-chemical properties were investigated by filtration of seawater supplemented with the antiscalants through flat-sheet RO membrane and changes in surface zeta potential and hydrophobicity were delineated. Adsorption of antiscalants to polyamide surfaces simulating RO membrane's polyamide layer and their effects on the consequent bacterial adhesion was tested using a quartz crystal microbalance with dissipation monitoring technology (QCM-D) and direct fluorescent microscopy. A significant increase in biofilm formation rate on RO membranes surface was observed in the presence of both types of antiscalants. Polyacrylate-based antiscalant was shown to enhance initial cell attachment as observed with the QCM-D and a parallel plate flow cell, due to rendering the polyamide surface more hydrophobic. Polyphosphonate-based antiscalants also increased biofilm formation rate, most likely by serving as an additional source of phosphorous to the seawater microbial population. A thicker biofilm layer was formed on the RO membrane when the polyacrylate-based antiscalant was used. Following

  11. Planets and Stellar Activity: Hide and Seek in the CoRoT-7 system

    NASA Astrophysics Data System (ADS)

    Haywood, R. D.; Cameron, A. C.; Queloz, D.; Barros, S. C. C.; Deleuil, M.; Fares, R.; Gillon, M.; Hatzes, A.; Lanza, A. F.; Lovis, C.; Moutou, C.; Pepe, F.; Pollacco, D.; Santerne, A.; Ségransan, D.; Unruh, Y.

    2014-01-01

    Since the discovery of the transiting Super-Earth CoRoT-7b, several investigations have been made of the number and precise masses of planets present in the system, but they all yield different results, owing to the star's high level of activity. Radial velocity (RV) variations induced by stellar activity therefore need to be modelled and removed to allow a reliable detection of all planets in the system. We re-observed CoRoT-7 in January 2012 with both HARPS and the CoRoT satellite, so that we now have the benefit of simultaneous RV and photometric data. We fitted the off-transit variations in the CoRoT lightcurve using a harmonic decomposition similar to that implemented in Queloz et al. (2009). This fit was then used to model the stellar RV contribution, according to the methods described by Aigrain et al. (2011). This model was incorporated into a Monte Carlo Markov Chain in order to make a precise determination of the orbits of CoRoT-7b and CoRoT-7c. We also assess the evidence for the presence of one or two additional planetary companions.

  12. Expression of CD45RO on circulating CD19+ B-cells in Crohn's disease.

    PubMed Central

    Yacyshyn, B R; Pilarski, L M

    1993-01-01

    Crohn's disease is an immunoregulatory disorder of the intestine that can be associated with systemic manifestations. This study analysed B-cell differentiation antigens to identify B-cell subpopulations unique to patients with Crohn's disease. CD45 isoform expression was used as an indicator of B-cell differentiation stage. This work shows that B-cells in blood and gut of patients with Crohn's disease are at an advanced stage of differentiation based on their unusual presentation of transitional (RA+ RO+) and late stage (RO+)CD45 isoforms on lamina propria lymphocytes, whereas normal intestinal lamina propria lymphocytes B-cells express primarily CD45RA. Crohn's disease patients had heightened expression of the CD45RO isoform on CD19+ lamina propria lymphocytes, and was found in a statistically significant proportion of Crohn's peripheral blood mononuclear cells (PBMC) where CD19+ PBMC had an expression pattern affecting an unexpectedly high proportion of these differentiated or late stage CD45RO+ B-cells. The expression of CD45RO varied greatly among CD19+ PBMC from patients with Crohn's disease, so multiple regression analysis was performed between these CD45 isoforms and several clinical parameters. After grouping high and low CD45RO expression on CD19+ B-cells, a significant statistical difference was found between high Crohn's disease activity index (CDAI) and low CDAI Crohn's disease patients respectively. PMID:7506695

  13. Characterisation of residual ionospheric errors in bending angles using GNSS RO end-to-end simulations

    NASA Astrophysics Data System (ADS)

    Liu, C. L.; Kirchengast, G.; Zhang, K. F.; Norman, R.; Li, Y.; Zhang, S. C.; Carter, B.; Fritzer, J.; Schwaerz, M.; Choy, S. L.; Wu, S. Q.; Tan, Z. X.

    2013-09-01

    Global Navigation Satellite System (GNSS) radio occultation (RO) is an innovative meteorological remote sensing technique for measuring atmospheric parameters such as refractivity, temperature, water vapour and pressure for the improvement of numerical weather prediction (NWP) and global climate monitoring (GCM). GNSS RO has many unique characteristics including global coverage, long-term stability of observations, as well as high accuracy and high vertical resolution of the derived atmospheric profiles. One of the main error sources in GNSS RO observations that significantly affect the accuracy of the derived atmospheric parameters in the stratosphere is the ionospheric error. In order to mitigate the effect of this error, the linear ionospheric correction approach for dual-frequency GNSS RO observations is commonly used. However, the residual ionospheric errors (RIEs) can be still significant, especially when large ionospheric disturbances occur and prevail such as during the periods of active space weather. In this study, the RIEs were investigated under different local time, propagation direction and solar activity conditions and their effects on RO bending angles are characterised using end-to-end simulations. A three-step simulation study was designed to investigate the characteristics of the RIEs through comparing the bending angles with and without the effects of the RIEs. This research forms an important step forward in improving the accuracy of the atmospheric profiles derived from the GNSS RO technique.

  14. Effects of the 5-HT(6) receptor antagonist Ro 04-6790 on learning consolidation.

    PubMed

    Meneses, A

    2001-01-08

    The 5-HT(6) receptor antagonist Ro-04-6790 or 8-OH-DPAT injection improved learning consolidation on an autoshaping task, while mCPP, scopolamine and dizocilpine decreased the performance. The effect induced by scopolamine, but not that induced by mCPP, was reversed completely by Ro-04-6790, while dizocilpine effect was antagonized partially. Nevertheless, ritanserin or WAY 100635, but not Ro 04-6790, antagonized the 8-OH-DPAT facilitatory effects on learning consolidation. As WAY 100635 did not modify the Ro 04-6790 facilitatory effect, hence 5-HT(1A), and/or 5-HT(7), but not 5-HT(6), receptors might mediate the 8-OH-DPAT facilitatory effect on learning consolidation. Since, the Ro 04-6790 facilitatory effect was unaffected by 5-HT(1A), 5-HT(2A)/(2B)/(2C), 5-HT(3) or 5-HT(4) receptor blockade, thereby, the facilitatory effect induced by Ro 04-6790 involved specifically 5-HT(6) receptors. Indeed, the present data provide further support to the notion that, 5-HT(6) receptors play a significant part in the learning consolidation under normal and dysfunctional memory conditions.

  15. Increasing RO efficiency by chemical-free ion-exchange and Donnan dialysis: Principles and practical implications.

    PubMed

    Vanoppen, Marjolein; Stoffels, Griet; Demuytere, Célestin; Bleyaert, Wouter; Verliefde, Arne R D

    2015-09-01

    Ion-exchange (IEX) and Donnan dialysis (DD) are techniques which can selectively remove cations, limiting scaling in reverse osmosis (RO). If the RO concentrate could be recycled for regeneration of these pre-treatment techniques, RO recovery could be largely increased without the need for chemical addition or additional technologies. In this study, two different RO feed streams (treated industrial waste water and simple tap water) were tested in the envisioned IEX-RO and DD-RO hybrids including RO concentrate recycling. The efficiency of multivalent cation removal depends mainly on the ratio of monovalent to multivalent cations in the feed stream, influencing the ion-exchange efficiency in both IEX and DD. Since the mono-to-multivalent ratio was very high in the waste water, the RO recovery could potentially be increased to 92%. For the tap water, these high RO recoveries could only be reached by adding additional NaCl, because of the low initial monovalent to multivalent ratio in the feed. In both cases, the IEX-RO hybrid proved to be most cost-efficient, due to the high current cost of the membranes used in DD. The membrane cost would have to decrease from ±300 €/m² to 10-30 €/m² - comparable to current reverse osmosis membranes - to achieve a comparable cost. In conclusion, the recycling of RO concentrate to regenerate ion exchange pre-treatment techniques for RO is an interesting option to increase RO recovery without addition of chemicals, but only at high monovalent/multivalent cation-ratios in the feed stream.

  16. Transiting exoplanets from the CoRoT space mission. VIII. CoRoT-7b: the first super-Earth with measured radius

    NASA Astrophysics Data System (ADS)

    Léger, A.; Rouan, D.; Schneider, J.; Barge, P.; Fridlund, M.; Samuel, B.; Ollivier, M.; Guenther, E.; Deleuil, M.; Deeg, H. J.; Auvergne, M.; Alonso, R.; Aigrain, S.; Alapini, A.; Almenara, J. M.; Baglin, A.; Barbieri, M.; Bruntt, H.; Bordé, P.; Bouchy, F.; Cabrera, J.; Catala, C.; Carone, L.; Carpano, S.; Csizmadia, Sz.; Dvorak, R.; Erikson, A.; Ferraz-Mello, S.; Foing, B.; Fressin, F.; Gandolfi, D.; Gillon, M.; Gondoin, Ph.; Grasset, O.; Guillot, T.; Hatzes, A.; Hébrard, G.; Jorda, L.; Lammer, H.; Llebaria, A.; Loeillet, B.; Mayor, M.; Mazeh, T.; Moutou, C.; Pätzold, M.; Pont, F.; Queloz, D.; Rauer, H.; Renner, S.; Samadi, R.; Shporer, A.; Sotin, Ch.; Tingley, B.; Wuchterl, G.; Adda, M.; Agogu, P.; Appourchaux, T.; Ballans, H.; Baron, P.; Beaufort, T.; Bellenger, R.; Berlin, R.; Bernardi, P.; Blouin, D.; Baudin, F.; Bodin, P.; Boisnard, L.; Boit, L.; Bonneau, F.; Borzeix, S.; Briet, R.; Buey, J.-T.; Butler, B.; Cailleau, D.; Cautain, R.; Chabaud, P.-Y.; Chaintreuil, S.; Chiavassa, F.; Costes, V.; Cuna Parrho, V.; de Oliveira Fialho, F.; Decaudin, M.; Defise, J.-M.; Djalal, S.; Epstein, G.; Exil, G.-E.; Fauré, C.; Fenouillet, T.; Gaboriaud, A.; Gallic, A.; Gamet, P.; Gavalda, P.; Grolleau, E.; Gruneisen, R.; Gueguen, L.; Guis, V.; Guivarc'h, V.; Guterman, P.; Hallouard, D.; Hasiba, J.; Heuripeau, F.; Huntzinger, G.; Hustaix, H.; Imad, C.; Imbert, C.; Johlander, B.; Jouret, M.; Journoud, P.; Karioty, F.; Kerjean, L.; Lafaille, V.; Lafond, L.; Lam-Trong, T.; Landiech, P.; Lapeyrere, V.; Larqué, T.; Laudet, P.; Lautier, N.; Lecann, H.; Lefevre, L.; Leruyet, B.; Levacher, P.; Magnan, A.; Mazy, E.; Mertens, F.; Mesnager, J.-M.; Meunier, J.-C.; Michel, J.-P.; Monjoin, W.; Naudet, D.; Nguyen-Kim, K.; Orcesi, J.-L.; Ottacher, H.; Perez, R.; Peter, G.; Plasson, P.; Plesseria, J.-Y.; Pontet, B.; Pradines, A.; Quentin, C.; Reynaud, J.-L.; Rolland, G.; Rollenhagen, F.; Romagnan, R.; Russ, N.; Schmidt, R.; Schwartz, N.; Sebbag, I.; Sedes, G.; Smit, H.; Steller, M. B.; Sunter, W.; Surace, C.; Tello, M.; Tiphène, D.; Toulouse, P.; Ulmer, B.; Vandermarcq, O.; Vergnault, E.; Vuillemin, A.; Zanatta, P.

    2009-10-01

    Aims: We report the discovery of very shallow (Δ F/F ≈ 3.4× 10-4), periodic dips in the light curve of an active V = 11.7 G9V star observed by the CoRoT satellite, which we interpret as caused by a transiting companion. We describe the 3-colour CoRoT data and complementary ground-based observations that support the planetary nature of the companion. Methods: We used CoRoT colours information, good angular resolution ground-based photometric observations in- and out- of transit, adaptive optics imaging, near-infrared spectroscopy, and preliminary results from radial velocity measurements, to test the diluted eclipsing binary scenarios. The parameters of the host star were derived from optical spectra, which were then combined with the CoRoT light curve to derive parameters of the companion. Results: We examined all conceivable cases of false positives carefully, and all the tests support the planetary hypothesis. Blends with separation >0.40´´or triple systems are almost excluded with a 8 × 10-4 risk left. We conclude that, inasmuch we have been exhaustive, we have discovered a planetary companion, named CoRoT-7b, for which we derive a period of 0.853 59 ± 3 × 10-5 day and a radius of Rp = 1.68 ± 0.09 R_Earth. Analysis of preliminary radial velocity data yields an upper limit of 21 M_Earth for the companion mass, supporting the finding. Conclusions: CoRoT-7b is very likely the first Super-Earth with a measured radius. This object illustrates what will probably become a common situation with missions such as Kepler, namely the need to establish the planetary origin of transits in the absence of a firm radial velocity detection and mass measurement. The composition of CoRoT-7b remains loosely constrained without a precise mass. A very high surface temperature on its irradiated face, ≈1800-2600 K at the substellar point, and a very low one, ≈50 K, on its dark face assuming no atmosphere, have been derived. The CoRoT space mission, launched on 27

  17. Angiogenesis Inhibitors

    MedlinePlus

    ... inhibitors: current strategies and future prospects. CA: A Cancer Journal for Clinicians 2010; 60(4):222–243. [PubMed Abstract] Chen HX, Cleck JN. Adverse effects of anticancer agents that target the VEGF pathway. Nature Reviews Clinical Oncology 2009; 6(8):465– ...

  18. Carboxylesterase inhibitors

    PubMed Central

    Hatfield, M. Jason; Potter, Philip M.

    2011-01-01

    Introduction Carboxylesterases play major roles in the hydrolysis of numerous therapeutically active compounds. This is, in part, due to the prevalence of the ester moiety in these small molecules. However, the impact these enzymes may play on drug stability and pharmacokinetics is rarely considered prior to molecule development. Therefore, the application of selective inhibitors of this class of proteins may have utility in modulating the metabolism, distribution and toxicity of agents that are subjected to enzyme hydrolysis. Areas covered This review details the development of all such compounds dating back to 1986, but principally focuses on the very recent identification of selective human carboxylesterases inhibitors. Expert opinion The implementation of carboxylesterase inhibitors may significantly revolutionize drug discovery. Such molecules may allow for improved efficacy of compounds inactivated by this class of enzymes and/or reduce the toxicity of agents that are activated by these proteins. Furthermore, since lack of carboxylesterase activity appears to have no obvious biological consequence, these compounds could be applied in combination with virtually any esterified drug. Therefore, inhibitors of these proteins may have utility in altering drug hydrolysis and distribution in vivo. The characteristics, chemical and biological properties, and potential uses of such agents, are discussed here. PMID:21609191

  19. RoBlock: a prototype autonomous manufacturing cell

    NASA Astrophysics Data System (ADS)

    Baekdal, Lars K.; Balslev, Ivar; Eriksen, Rene D.; Jensen, Soren P.; Jorgensen, Bo N.; Kirstein, Brian; Kristensen, Bent B.; Olsen, Martin M.; Perram, John W.; Petersen, Henrik G.; Petersen, Morten L.; Ruhoff, Peter T.; Skjolstrup, Carl E.; Sorensen, Anders S.; Wagenaar, Jeroen M.

    2000-10-01

    RoBlock is the first phase of an internally financed project at the Institute aimed at building a system in which two industrial robots suspended from a gantry, as shown below, cooperate to perform a task specified by an external user, in this case, assembling an unstructured collection of colored wooden blocks into a specified 3D pattern. The blocks are identified and localized using computer vision and grasped with a suction cup mechanism. Future phases of the project will involve other processes such as grasping and lifting, as well as other types of robot such as autonomous vehicles or variable geometry trusses. Innovative features of the control software system include: The use of an advanced trajectory planning system which ensures collision avoidance based on a generalization of the method of artificial potential fields, the use of a generic model-based controller which learns the values of parameters, including static and kinetic friction, of a detailed mechanical model of itself by comparing actual with planned movements, the use of fast, flexible, and robust pattern recognition and 3D-interpretation strategies, integration of trajectory planning and control with the sensor systems in a distributed Java application running on a network of PC's attached to the individual physical components. In designing this first stage, the aim was to build in the minimum complexity necessary to make the system non-trivially autonomous and to minimize the technological risks. The aims of this project, which is planned to be operational during 2000, are as follows: To provide a platform for carrying out experimental research in multi-agent systems and autonomous manufacturing systems, to test the interdisciplinary cooperation architecture of the Maersk Institute, in which researchers in the fields of applied mathematics (modeling the physical world), software engineering (modeling the system) and sensor/actuator technology (relating the virtual and real worlds) could

  20. MBR/RO/ozone processes for TFT-LCD industrial wastewater treatment and recycling.

    PubMed

    Chen, T K; Ni, C H; Chan, Y C; Lu, M C

    2005-01-01

    This research is mainly to explore the treatment capacity for TFT-LCD industrial wastewater recycling by the processes combined with membrane bioreactor (MBR), reverse osmosis (RO) and ozone(O3). The organic wastewater from the TFT-LCD industry was selected as the target. MBR, RO and ozone plants were established for evaluation. An MBR plant consisted of a 2-stage anoxic/aerobic bioreactor and an immersed UF membrane unit was employed. The effluent of MBR was conducted into the RO system then into the ozone system. The RO system consisted of a spiral membrane in the vessel. One bubble column, 75 cm high and diameter 5 cm, were used as the ozonation reactor. On the bottom of ozonation reactor is a porous diffuser for releasing gas, with an aperture of 100 microm (0.1 cm). Over the whole experimental period, the MBR process achieved a satisfactory organic removal. The COD could be removed with an average of over 98.5%. For the TOC item, the average removal efficiency was 97.4%. The stable effluent quality and satisfactory removal performance were ensured by the efficient interception performance of an immersed UF membrane device incorporated with the biological reactor. Moreover, the MBR effluent did not contain any suspended solids and the SDI value was under 3. After the treatment of RO, excellent water quality was found. The water quality of permeate was under 5 mg/I, 2 mg/l and 50 micros/cm for COD, TOC and conductivity respectively. The treated water can be recycled and reused for the cooling tower make-up water or other purposes. After the treatment of ozone, the treated water quality was under 5 mg/l and 0.852 mg/l for COD and TOC respectively. The test results of MBR, MBR/RO and MBR/RO/ozone processes were compared as possible appropriate treatment technologies applied in TFT-LCD industrial wastewater reuse and recycling.

  1. Does the benzodiazepine antagonist Ro 15-1788 antagonize the action of ethanol?

    PubMed

    Klotz, U; Ziegler, G; Rosenkranz, B; Mikus, G

    1986-11-01

    Ethanol aggravates benzodiazepine-induced central nervous depression by pharmacokinetic and/or pharmacodynamic interactions and Ro 15-1788 reverses promptly the hypnotic effects of benzodiazepines. We therefore studied the acute effects of Ro 15-1788 on the ethanol-induced sedation in six healthy male subjects. Subsequently to an oral loading dose (0.54 g ethanol kg-1) ethanol was infused for 4 h (0.15 g ethanol kg-1 h-1) and steady state blood levels between 0.9 to 1.2 g l-1 were reached within 2 h. At steady state and during the elimination phase of ethanol an intravenous bolus of 0.5 mg Ro 15-1788 or placebo was administered in a randomized, double-blind crossover fashion. The marked sedative effects of ethanol as assessed by visual analogue scales (2 to 6 fold increase in the sedation index), and choice reaction time (25 to 40% prolongation) were not affected by Ro 15-1788. However, the pharmaco-EEG indicated that Ro 15-1788 seems to reverse transiently the ethanol-induced changes in total alpha, delta, and slow alpha bands. There was no pharmacokinetic interaction between both agents since elimination of Ro 15-1788 (t1/2 = 1.2 +/- 0.7 h) and of ethanol (0.17 +/- 0.02 g l-1 h-1) were in good agreement with control values. Thus, it could be concluded that Ro 15-1788 might affect for a short while the action of ethanol by interfering with the benzodiazepine receptors.

  2. Preclinical profile of a potent gamma-secretase inhibitor targeting notch signaling with in vivo efficacy and pharmacodynamic properties.

    PubMed

    Luistro, Leopoldo; He, Wei; Smith, Melissa; Packman, Kathryn; Vilenchik, Maria; Carvajal, Daisy; Roberts, John; Cai, James; Berkofsky-Fessler, Windy; Hilton, Holly; Linn, Michael; Flohr, Alexander; Jakob-Røtne, Roland; Jacobsen, Helmut; Glenn, Kelli; Heimbrook, David; Boylan, John F

    2009-10-01

    Notch signaling is an area of great interest in oncology. RO4929097 is a potent and selective inhibitor of gamma-secretase, producing inhibitory activity of Notch signaling in tumor cells. The RO4929097 IC50 in cell-free and cellular assays is in the low nanomolar range with >100-fold selectivity with respect to 75 other proteins of various types (receptors, ion channels, and enzymes). RO4929097 inhibits Notch processing in tumor cells as measured by the reduction of intracellular Notch expression by Western blot. This leads to reduced expression of the Notch transcriptional target gene Hes1. RO4929097 does not block tumor cell proliferation or induce apoptosis but instead produces a less transformed, flattened, slower-growing phenotype. RO4929097 is active following oral dosing. Antitumor activity was shown in 7 of 8 xenografts tested on an intermittent or daily schedule in the absence of body weight loss or Notch-related toxicities. Importantly, efficacy is maintained after dosing is terminated. Angiogenesis reverse transcription-PCR array data show reduced expression of several key angiogenic genes. In addition, comparative microarray analysis suggests tumor cell differentiation as an additional mode of action. These preclinical results support evaluation of RO4929097 in clinical studies using an intermittent dosing schedule. A multicenter phase I dose escalation study in oncology is under way.

  3. Speckle Imaging of Kepler and CoRoT Exo-planet Transit Candidate Stars

    NASA Astrophysics Data System (ADS)

    Howell, Steve B.; Horch, Elliott; Sherry, William; Ciardi, David

    2010-08-01

    Kepler and CoRoT are complementary space missions dedicated to the detection of exoplanets. The primary science goal of CoRoT is to find Neptune-sized (>3 Earth radii) planets in intermediate orbits, while the prime science goal of Kepler is to find Earth-sized planets (<3 Earth radii) in year-long orbits. Both missions employ the photometric transit method and both spacecraft are performing well with nominal operation of the spacecraft, telescopes, electronics, and instruments. As with ground-based surveys, Kepler and CoRoT candidates need to be screened for background eclipsing binary stars which, when photometrically blended with the primary target, can mimic exo-planetary transits. The list of candidate transiting planets found by Kepler/CoRoT requires follow-up to ascertain probable or certain exo- planet detection. While Earth-sized (and Neptune-sized in long orbital periods) exo-planets can not currently (easily) be confirmed from the ground, many of the false positive eliminations steps can be performed by ground-based observations. Follow-up for Kepler exo-planet candidates is now aimed at Neptune-size and smaller planets in longer period orbits. This proposal aims to obtain high resolution speckle imaging to observe Kepler/CoRoT exo-planet transit candidates in order to eliminate the largest false positive contributor in any transit search - background eclipsing binary stars or faint companion stars.

  4. Abnormal clinical pharmacokinetics of the developmental radiosensitizers pimonidazole (Ro 03-8799) and etanidazole (SR 2508)

    SciTech Connect

    Maughan, T.S.; Newman, H.F.; Bleehen, N.M.; Ward, R.; Workman, P. )

    1990-05-01

    The hypoxic cell radiosensitizers Ro 03-8799 (pimonidazole) and SR 2508 (etanidazole) are under evaluation as single agents (Phase III) and in combination (Phase I). Ro 03-8799 produces an acute, transient central nervous system syndrome, whereas SR 2508 causes cumulative, peripheral neurotoxicity; both effects are dose-limiting. Pharmacokinetic studies have shown the importance of area under the plasma drug concentration versus time curve (AUC) in predicting the risk of peripheral neuropathy. Most patients have very similar pharmacokinetic parameters. This study reports 2/25 patients receiving 0.75 g/m2 Ro 03-8799 plus 2.0 g/m2 SR 2508 who showed significant discrepancies in drug handling. One patient exhibited a markedly elevated AUC and prolonged t1/2 beta for SR 2508 and this was associated with an unusually rapid onset of peripheral neuropathy. A second patient showed normal handling of SR 2508 but prolonged values for both t1/2 alpha and t1/2 beta for Ro 03-8799 and unusually low levels of its N-oxide metabolite. In addition a low peak Ro 03-8799 concentration combined with a very high volume of distribution was found in this patient, leading to a normal AUC value and toxicity profile. Both patients exhibited a relatively low creatinine clearance. The mechanisms which may underlie these findings are discussed, and the importance of pharmacokinetic monitoring in the use of these agents is emphasized.

  5. Data Analysis Provenance: Use Case for Exoplanet Search in CoRoT Database

    NASA Astrophysics Data System (ADS)

    de Souza, L.; Salete Marcon Gomes Vaz, M.; Emílio, M.; Ferreira da Rocha, J. C.; Janot Pacheco, E.; Carlos Boufleur, R.

    2012-09-01

    CoRoT (COnvection Rotation and Planetary Transits) is a mission led by the French national space agency CNES, in collaboration with Austria, Spain, Germany, Belgium and Brazil. The mission priority is dedicated to exoplanet search and stellar seismology. CoRoT light curves database became public after one year of their delivery to the CoRoT Co-Is, following the CoRoT data policy. The CoRoT archive contains thousands of light curves in FITS format. Several exoplanet search algorithms require detrend algorithms to remove both stellar and instrumental signal, improving the chance to detect a transit. Different detrend and transit detection algorithms can be applied to the same database. Tracking the origin of the information and how the data was derived in each level in the data analysis process is essential to allow sharing, reuse, reprocessing and further analysis. This work aims at applying a formalized and codified knowledge model by means of domain ontology. It allows to enrich the data analysis with semantic and standardization. It holds the provenance information in the database for a posteriori recovers by humans or software agents.

  6. Transiting exoplanets from the CoRoT space mission. XXVII. CoRoT-28b, a planet orbiting an evolved star, and CoRoT-29b, a planet showing an asymmetric transit

    NASA Astrophysics Data System (ADS)

    Cabrera, J.; Csizmadia, Sz.; Montagnier, G.; Fridlund, M.; Ammler-von Eiff, M.; Chaintreuil, S.; Damiani, C.; Deleuil, M.; Ferraz-Mello, S.; Ferrigno, A.; Gandolfi, D.; Guillot, T.; Guenther, E. W.; Hatzes, A.; Hébrard, G.; Klagyivik, P.; Parviainen, H.; Pasternacki, Th.; Pätzold, M.; Sebastian, D.; Tadeu dos Santos, M.; Wuchterl, G.; Aigrain, S.; Alonso, R.; Almenara, J.-M.; Armstrong, J. D.; Auvergne, M.; Baglin, A.; Barge, P.; Barros, S. C. C.; Bonomo, A. S.; Bordé, P.; Bouchy, F.; Carpano, S.; Chaffey, C.; Deeg, H. J.; Díaz, R. F.; Dvorak, R.; Erikson, A.; Grziwa, S.; Korth, J.; Lammer, H.; Lindsay, C.; Mazeh, T.; Moutou, C.; Ofir, A.; Ollivier, M.; Pallé, E.; Rauer, H.; Rouan, D.; Samuel, B.; Santerne, A.; Schneider, J.

    2015-07-01

    Context. We present the discovery of two transiting extrasolar planets by the satellite CoRoT. Aims: We aim at a characterization of the planetary bulk parameters, which allow us to further investigate the formation and evolution of the planetary systems and the main properties of the host stars. Methods: We used the transit light curve to characterize the planetary parameters relative to the stellar parameters. The analysis of HARPS spectra established the planetary nature of the detections, providing their masses. Further photometric and spectroscopic ground-based observations provided stellar parameters (log g, Teff, v sin i) to characterize the host stars. Our model takes the geometry of the transit to constrain the stellar density into account, which when linked to stellar evolutionary models, determines the bulk parameters of the star. Because of the asymmetric shape of the light curve of one of the planets, we had to include the possibility in our model that the stellar surface was not strictly spherical. Results: We present the planetary parameters of CoRoT-28b, a Jupiter-sized planet (mass 0.484 ± 0.087 MJup; radius 0.955 ± 0.066 RJup) orbiting an evolved star with an orbital period of 5.208 51 ± 0.000 38 days, and CoRoT-29b, another Jupiter-sized planet (mass 0.85 ± 0.20 MJup; radius 0.90 ± 0.16 RJup) orbiting an oblate star with an orbital period of 2.850 570 ± 0.000 006 days. The reason behind the asymmetry of the transit shape is not understood at this point. Conclusions: These two new planetary systems have very interesting properties and deserve further study, particularly in the case of the star CoRoT-29. The CoRoT space mission, launched on December 27th 2006, was developed and is operated by CNES, with the contribution of Austria, Belgium, Brazil, ESA (RSSD and Science Programme), Germany, and Spain. Based on observations obtained with the Nordic Optical Telescope, operated on the island of La Palma jointly by Denmark, Finland, Iceland

  7. Research and development of Ro-boat: an autonomous river cleaning robot

    NASA Astrophysics Data System (ADS)

    Sinha, Aakash; Bhardwaj, Prashant; Vaibhav, Bipul; Mohommad, Noor

    2013-12-01

    Ro-Boat is an autonomous river cleaning intelligent robot incorporating mechanical design and computer vision algorithm to achieve autonomous river cleaning and provide a sustainable environment. Ro-boat is designed in a modular fashion with design details such as mechanical structural design, hydrodynamic design and vibrational analysis. It is incorporated with a stable mechanical system with air and water propulsion, robotic arms and solar energy source and it is proceed to become autonomous by using computer vision. Both "HSV Color Space" and "SURF" are proposed to use for measurements in Kalman Filter resulting in extremely robust pollutant tracking. The system has been tested with successful results in the Yamuna River in New Delhi. We foresee that a system of Ro-boats working autonomously 24x7 can clean a major river in a city on about six months time, which is unmatched by alternative methods of river cleaning.

  8. WE-B-Exhibit Hall-01: Ask the RO-ILS Experts

    SciTech Connect

    Ezzell, G; Sanscrainte, E; Tomlinson, C

    2015-06-15

    Have a question about RO-ILS: Radiation Oncology Incident Learning System™, or interested in learning more? Sponsored by the American Society for Radiation Oncology (ASTRO) and AAPM, RO-ILS is the only medical specialty society-sponsored incident learning system for radiation oncology. It facilitates safer and higher quality care in radiation oncology by providing a mechanism for shared learning in a secure and non-punitive environment. Please join our RO-ILS experts for a question and answer session on Wednesday, July 15th at 8:30 in the Partners in Solutions Room in Exhibit Hall C. Our experts include: Gary Ezzell, PhD, Mayo Clinic Arizona, [Brett Miller, Phillip Beron, and Derek Brown], Emily Sanscrainte from Clarity PSO and Cindy Tomlinson, MPP, ASTRO.

  9. Removal of bisphenol A (BPA) from water by various nanofiltration (NF) and reverse osmosis (RO) membranes.

    PubMed

    Yüksel, Suna; Kabay, Nalan; Yüksel, Mithat

    2013-12-15

    The removal of an endocrine disrupting compound, bisphenol A (BPA), from model solutions by selected nanofiltration (NF) and reverse osmosis (RO) membranes was studied. The commercially available membranes NF 90, NF 270, XLE BWRO, BW 30 (Dow FilmTech), CE BWRO and AD SWRO (GE Osmonics) were used to compare their performances for BPA removal. The water permeability coefficients, rejection of BPA and permeate flux values were calculated for all membranes used. No significant changes in their BPA removal were observed for all tight polyamide based NF and RO membranes tested except for loose NF 270 membrane. The polyamide based membranes exhibited much better performance than cellulose acetate membrane for BPA removal. Almost a complete rejection (≥ 98%) for BPA was obtained with three polyamide based RO membranes (BW 30, XLE BWRO and AD SWRO). But cellulose acetate based CE BWRO membrane offered a low and variable (10-40%) rejection for BPA.

  10. Local rotundity structure of Cesàro-Orlicz sequence spaces

    NASA Astrophysics Data System (ADS)

    Foralewski, Pawel; Hudzik, Henryk; Szymaszkiewicz, Alicja

    2008-09-01

    Some criteria for extreme points and strong U-points in Cesàro-Orlicz spaces are given. In consequence we find a Cesàro-Orlicz sequence space different from c0 which has no extreme points. Some examples show that in these spaces the notion of the strong U-point is essentially stronger than the notion of the extreme point. Various examples presented in this paper show that there are some differences between criteria for extreme points and strong U-points in Orlicz spaces and in Cesàro-Orlicz spaces. We also show that the uniqueness of the local best approximation needs the notion of SU-point, that is, the notion of the extreme point is not strong enough here.

  11. On the spectrum of the Cesàro operator on spaces of analytic functions

    NASA Astrophysics Data System (ADS)

    Persson, Anna-Maria

    2008-04-01

    This paper concerns the Cesàro operator acting on various spaces of analytic functions on the unit disc. The remarkable fact that this operator is subnormal when acting on the Hardy space H2 has lead to extensive studies of its spectral picture on other spaces of this type. We present some of the methods that have been used to obtain information about the spectrum of the Cesàro operator acting on Hardy and Bergman spaces and give a unified approach to these problems which also yields new results in this direction. In particular, we prove that the Cesàro operator is subdecomposable on H1 and on the standard weighted Bergman spaces , [alpha][greater-or-equal, slanted]0.

  12. The study of Be stars with the CoRoT satellite

    NASA Astrophysics Data System (ADS)

    Diago, P. D.; Gutierrez-Soto, J.; Fabregat, J.; Suso, J.; COROT Be Team

    2011-11-01

    The CoRoT space mission, launched in December 2006, is a spacecraft devoted to the study of the stellar interiors and the exo-planet search. Concerning the seismology of the Be stars, the presence of pulsations in late-type Be stars is still a matter of controversy. It constitutes an important issue to establish the relationship between non-radial pulsations and the mass-loss mechanism in Be stars. In this field, the CoRoT satellite is providing data with an unprecedent quality and precision that is confirming non-radial pulsations in Be stars. The CoRoT Be Team is an international collaboration composed by members from France, Spain, Brazil and Belgium and is in charge of the exploitation and analysis of the Be stars data. In this work we present the highlighted results of the observed Be stars by CoRoT and the future prospects of the CoRoT Be Team. These results include the detection of the Be star HD 49 330 during an outburst phase and the measurement of the change in the oscillation spectrum during this rare event. These observations gave insight into the nature of the explosion. It will help to solve a question that has been pending for years: are oscillations the cause of the outbursts? Moreover, for the first time, the CoRoT satellite has detected simultaneously the rotational and the pulsational frequencies for the Be star HD 50 209, which constitutes a proof of the presence of pulsations in the Be stars. %J Highlights of Spanish Astrophysics VI, Proceedings of the IX Scientific Meeting of the Spanish Astronomical Society (SEA), held in Madrid, September 13 - 17, 2010, Eds.: M. R. Zapatero Osorio, J. Gorgas, J. Maiz Apellaniz, J. R. Pardo, and A. Gil de Paz., p. 531-531

  13. Planetary transit candidates in the CoRoT-SRc01 field

    NASA Astrophysics Data System (ADS)

    Erikson, A.; Santerne, A.; Renner, S.; Barge, P.; Aigrain, S.; Alapini, A.; Almenara, J.-M.; Alonso, R.; Auvergne, M.; Baglin, A.; Benz, W.; Bonomo, A. S.; Bordé, P.; Bouchy, F.; Bruntt, H.; Cabrera, J.; Carone, L.; Carpano, S.; Csizmadia, Sz.; Deleuil, M.; Deeg, H. J.; Díaz, R. F.; Dvorak, R.; Ferraz-Mello, S.; Fridlund, M.; Gandolfi, D.; Gazzano, J.-C.; Gillon, M.; Guenther, E. W.; Guillot, T.; Hatzes, A.; Hébrard, G.; Jorda, L.; Lammer, H.; Léger, A.; Llebaria, A.; Mayor, M.; Mazeh, T.; Moutou, C.; Ollivier, M.; Ofir, A.; Pätzold, M.; Pepe, F.; Pont, F.; Queloz, D.; Rabus, M.; Rauer, H.; Régulo, C.; Rouan, D.; Samuel, B.; Schneider, J.; Shporer, A.; Tingley, B.; Udry, S.; Wuchterl, G.

    2012-03-01

    Context. The space mission CoRoT is devoted to the analysis of stellar variability and the photometric detection of extrasolar planets. Aims: We present the list of planetary transit candidates detected in the first short run observed by CoRoT that targeted SRc01, towards the Galactic center in the direction of Aquila, which lasted from April to May 2007. Methods: Among the acquired data, we analyzed those for 1269 sources in the chromatic bands and 5705 in the monochromatic band. Instrumental noise and the stellar variability were treated with several detrending tools, to which several transit-search algorithms were subsequently applied. Results: Fifty-one sources were classified as planetary transit candidates and 26 were followed up with ground-based observations. Until now, no planet has been detected in the CoRoT data from the SRc01 field. The CoRoT space mission, launched on December 27th 2006, has been developed and is operated by CNES, with contributions from Austria, Belgium, Brazil, ESA, Germany, and Spain. The CoRoT data are available to the community from the CoRoT archive: http://idoc-corot.ias.u-psud.frBased in part on observations made with the 1.93-m telescope at Observatoire de Haute Provence (CNRS), France (SOPHIE Program 08A.PNP.MOUT).Based in part on observations made with the ESO-3.60-m telescope at La Silla Observatory (ESO), Chile (HARPS Program ESO - 081.C-0388) and with the ESO-VLT telescope at Paranal Observatory (ESO), Chile (FLAMES Program ESO - 081.C-0413).

  14. EXO-DAT: AN INFORMATION SYSTEM IN SUPPORT OF THE CoRoT/EXOPLANET SCIENCE

    SciTech Connect

    Deleuil, M.; Meunier, J. C.; Moutou, C.; Surace, C.; Barbieri, M.; Agneray, F.; Granet, Y.; Guterman, P.; Deeg, H. J.; Almenara, J. M.; Hodgkin, S.

    2009-08-15

    Exo-Dat is a database and an information system created primarily in support of the exoplanet program of the COnvection ROtation and planetary Transits (CoRoT) mission. In the directions of CoRoT pointings, it provides a united interface to several sets of data: stellar published catalogs, photometric and spectroscopic data obtained during the mission preparation, results from the mission and from follow-up observations, and several mission-specific technical parameters. The new photometric data constitute the subcatalog Exo-Cat, and give consistent 4-color photometry of 14.0 million stars with a completeness to 19th magnitude in the r-filter. It covers several zones in the galactic plane around CoRoT pointings, with a total area of 209 deg{sup 2}. This Exo-Dat information system provides essential technical support to the ongoing CoRoT light-curve analyses and ground-based follow-up by supplying additional complementary information such as the prior knowledge of the star's fundamental parameters or its contamination level inside the large CoRoT photometric mask. The database is fully interfaced with VO tools and thus benefits from existing visualization and analysis tools like TOPCAT or ALADIN. It is accessible to the CoRoT community through the Web, and will be gradually opened to the public. It is the ideal tool to prepare the foreseen statistical studies of the properties of the exoplanetary systems. As a VO-compliant system, such analyses could thus benefit from the most up-to-date classifier tools.

  15. Transiting exoplanets from the CoRoT space mission. XX. CoRoT-20b: A very high density, high eccentricity transiting giant planet

    NASA Astrophysics Data System (ADS)

    Deleuil, M.; Bonomo, A. S.; Ferraz-Mello, S.; Erikson, A.; Bouchy, F.; Havel, M.; Aigrain, S.; Almenara, J.-M.; Alonso, R.; Auvergne, M.; Baglin, A.; Barge, P.; Bordé, P.; Bruntt, H.; Cabrera, J.; Carpano, S.; Cavarroc, C.; Csizmadia, Sz.; Damiani, C.; Deeg, H. J.; Dvorak, R.; Fridlund, M.; Hébrard, G.; Gandolfi, D.; Gillon, M.; Guenther, E.; Guillot, T.; Hatzes, A.; Jorda, L.; Léger, A.; Lammer, H.; Mazeh, T.; Moutou, C.; Ollivier, M.; Ofir, A.; Parviainen, H.; Queloz, D.; Rauer, H.; Rodríguez, A.; Rouan, D.; Santerne, A.; Schneider, J.; Tal-Or, L.; Tingley, B.; Weingrill, J.; Wuchterl, G.

    2012-02-01

    We report the discovery by the CoRoT space mission of a new giant planet, CoRoT-20b. The planet has a mass of 4.24 ± 0.23 MJup and a radius of 0.84 ± 0.04 RJup. With a mean density of 8.87 ± 1.10 g cm-3, it is among the most compact planets known so far. Evolutionary models for the planet suggest a mass of heavy elements of the order of 800 M⊕ if embedded in a central core, requiring a revision either of the planet formation models or both planet evolution and structure models. We note however that smaller amounts of heavy elements are expected by more realistic models in which they are mixed throughout the envelope. The planet orbits a G-type star with an orbital period of 9.24 days and an eccentricity of 0.56.The star's projected rotational velocity is vsini = 4.5 ± 1.0 km s-1, corresponding to a spin period of 11.5 ± 3.1 days if its axis of rotation is perpendicular to the orbital plane. In the framework of Darwinian theories and neglecting stellar magnetic breaking, we calculate the tidal evolution of the system and show that CoRoT-20b is presently one of the very few Darwin-stable planets that is evolving toward a triple synchronous state with equality of the orbital, planetary and stellar spin periods. The CoRoT space mission, launched on December 27th 2006, has been developed and is operated by CNES, with the contribution of Austria, Belgium, Brazil, ESA (RSSD and Science Programme), Germany, and Spain.

  16. Transiting exoplanets from the CoRoT space mission. V. CoRoT-Exo-4b: stellar and planetary parameters

    NASA Astrophysics Data System (ADS)

    Moutou, C.; Bruntt, H.; Guillot, T.; Shporer, A.; Guenther, E.; Aigrain, S.; Almenara, J. M.; Alonso, R.; Auvergne, M.; Baglin, A.; Barbieri, M.; Barge, P.; Benz, W.; Bordé, P.; Bouchy, F.; Deeg, H. J.; de La Reza, R.; Deleuil, M.; Dvorak, R.; Erikson, A.; Fridlund, M.; Gillon, M.; Gondoin, P.; Hatzes, A.; Hébrard, G.; Jorda, L.; Kabath, P.; Lammer, H.; Léger, A.; Llebaria, A.; Loeillet, B.; Magain, P.; Mayor, M.; Mazeh, T.; Ollivier, M.; Pätzold, M.; Pepe, F.; Pont, F.; Queloz, D.; Rabus, M.; Rauer, H.; Rouan, D.; Schneider, J.; Udry, S.; Wuchterl, G.

    2008-09-01

    Aims: The CoRoT satellite has announced its fourth transiting planet (Aigrain et al. 2008, A&A, 488, L43) with space photometry. We describe and analyse complementary observations of this system performed to establish the planetary nature of the transiting body and to estimate the fundamental parameters of the planet and its parent star. Methods: We have analysed high precision radial-velocity data, ground-based photometry, and high signal-to-noise ratio spectroscopy. Results: The parent star CoRoT-Exo-4 (2MASS 06484671-0040219) is a late F-type star of mass of 1.16 M⊙ and radius of 1.17 R⊙. The planet has a circular orbit with a period of 9.20205 d. The planet radius is 1.19 R_Jup and the mass is 0.72 M_Jup. It is a gas-giant planet with a “normal” internal structure of mainly H and He. CoRoT-Exo-4b has the second longest period of the known transiting planets. It is an important discovery since it occupies an empty area in the mass-period diagram of transiting exoplanets. Based on observations obtained with CoRoT, a space project operated by the French Space Agency, CNES, with participation of the Science Programme of ESA, ESTEC/RSSD, Austria, Belgium, Brazil, Germany and Spain; and on observations made with the SOPHIE spectrograph at Observatoire de Haute Provence, France (PNP.07B.MOUT), and the HARPS spectrograph at ESO La Silla Observatory (079.C-0127/F). Table 2 and Fig. 5 are only available in electronic form at http://www.aanda.org

  17. CoRoT archive as a treasury of variable stars

    NASA Astrophysics Data System (ADS)

    Benko, Jozsef M.; Paparo, Margit

    2015-08-01

    The CoRoT satellite supported the scientific community by a huge data base of variable stars. The investigation of RR Lyrae stars (radially pulsating classical variable stars of high amplitude), especially benefit the continuous space data, due to long periodicity. The CoRoT RR Lyrae stars were intensively discussed in numerous papers in the last few years, but the latest runs have not been checked for finding RR Lyrae stars up to now. We found eight new RR Lyrae stars that we investigated for the lately localized characteristics of Blazhko RR Lyrae stars: the period doubling and additional modes. We present the preliminary results here.

  18. Fetal manifestations of maternal anti‐Ro and La antibodies – more than complete heart block

    PubMed Central

    2015-01-01

    Abstract Complete heart block (CHB) is a potentially fatal condition occurring in approximately 1:10000 fetuses. Whilst it is well recognised that maternal anti‐Ro and La antibodies are associated with fetal CHB, there are multiple other manifestations of fetal exposure to these autoantibodies which are not widely appreciated and rarely diagnosed. The importance of identifying affected fetuses lies in the significantly increased risk of recurrence in future pregnancies, and the potential for treatments which may modify this risk. This paper presents several cases to highlight the varying fetal presentations of maternal anti‐Ro and La antibodies. PMID:28191254

  19. Multiple star systems observed with CoRoT and Kepler

    NASA Astrophysics Data System (ADS)

    Southworth, John

    2015-09-01

    The CoRoT and Kepler satellites were the first space platforms designed to perform high-precision photometry for a large number of stars. Multiple systems display a wide variety of photometric variability, making them natural benefactors of these missions. I review the work arising from CoRoT and Kepler observations of multiple systems, with particular emphasis on eclipsing binaries containing giant stars, pulsators, triple eclipses and/or low-mass stars. Many more results remain untapped in the data archives of these missions, and the future holds the promise of K2, TESS and PLATO.

  20. Transiting exoplanets from the CoRoT space mission. III. The spectroscopic transit of CoRoT-Exo-2b with SOPHIE and HARPS

    NASA Astrophysics Data System (ADS)

    Bouchy, F.; Queloz, D.; Deleuil, M.; Loeillet, B.; Hatzes, A. P.; Aigrain, S.; Alonso, R.; Auvergne, M.; Baglin, A.; Barge, P.; Benz, W.; Bordé, P.; Deeg, H. J.; de La Reza, R.; Dvorak, R.; Erikson, A.; Fridlund, M.; Gondoin, P.; Guillot, T.; Hébrard, G.; Jorda, L.; Lammer, H.; Léger, A.; Llebaria, A.; Magain, P.; Mayor, M.; Moutou, C.; Ollivier, M.; Pätzold, M.; Pepe, F.; Pont, F.; Rauer, H.; Rouan, D.; Schneider, J.; Triaud, A. H. M. J.; Udry, S.; Wuchterl, G.

    2008-05-01

    We report on the spectroscopic transit of the massive hot-Jupiter CoRoT-Exo-2b observed with the high-precision spectrographs SOPHIE and HARPS. By modeling the radial velocity anomaly occurring during the transit due to the Rossiter-McLaughlin (RM) effect, we determine the sky-projected angle between the stellar spin and the planetary orbital axis to be close to zero λ = 7.2 ± 4.5 deg, and we secure the planetary nature of CoRoT-Exo-2b. We discuss the influence of the stellar activity on the RM modeling. Spectral analysis of the parent star from HARPS spectra are presented. Observations made with SOPHIE spectrograph at Observatoire de Haute Provence, France (PNP.07A.MOUT) and HARPS spectrograph at ESO La Silla Observatory (079.C-0127(F)). The CoRoT space mission, launched on December 27th 2006, has been developed and is operated by CNES, with the contribution of Austria, Belgium, Brasil, ESA, Germany, and Spain.

  1. Transiting exoplanets from the CoRoT space mission. II. CoRoT-Exo-2b: a transiting planet around an active G star

    NASA Astrophysics Data System (ADS)

    Alonso, R.; Auvergne, M.; Baglin, A.; Ollivier, M.; Moutou, C.; Rouan, D.; Deeg, H. J.; Aigrain, S.; Almenara, J. M.; Barbieri, M.; Barge, P.; Benz, W.; Bordé, P.; Bouchy, F.; de La Reza, R.; Deleuil, M.; Dvorak, R.; Erikson, A.; Fridlund, M.; Gillon, M.; Gondoin, P.; Guillot, T.; Hatzes, A.; Hébrard, G.; Kabath, P.; Jorda, L.; Lammer, H.; Léger, A.; Llebaria, A.; Loeillet, B.; Magain, P.; Mayor, M.; Mazeh, T.; Pätzold, M.; Pepe, F.; Pont, F.; Queloz, D.; Rauer, H.; Shporer, A.; Schneider, J.; Stecklum, B.; Udry, S.; Wuchterl, G.

    2008-05-01

    Context: The CoRoT mission, a pioneer in exoplanet searches from space, has completed its first 150 days of continuous observations of ~12 000 stars in the galactic plane. An analysis of the raw data identifies the most promising candidates and triggers the ground-based follow-up. Aims: We report on the discovery of the transiting planet CoRoT-Exo-2b, with a period of 1.743 days, and characterize its main parameters. Methods: We filter the CoRoT raw light curve of cosmic impacts, orbital residuals, and low frequency signals from the star. The folded light curve of 78 transits is fitted to a model to obtain the main parameters. Radial velocity data obtained with the SOPHIE, CORALIE and HARPS spectrographs are combined to characterize the system. The 2.5 min binned phase-folded light curve is affected by the effect of sucessive occultations of stellar active regions by the planet, and the dispersion in the out of transit part reaches a level of 1.09×10-4 in flux units. Results: We derive a radius for the planet of 1.465 ± 0.029 R_Jup and a mass of 3.31 ± 0.16 M_Jup, corresponding to a density of 1.31 ± 0.04 g/cm^3. The large radius of CoRoT-Exo-2b cannot be explained by current models of evolution of irradiated planets. Based on observations obtained with CoRoT, a space project operated by the French Space Agency, CNES, with participation of the Science Programme of ESA, ESTEC/RSSD, Austria, Belgium, Brazil, Germany and Spain; and on observations made with SOPHIE spectrograph at Observatoire de Haute Provence, France (PNP.07 A.MOUT), CORALIE, and HARPS spectrograph at ESO La Silla Observatroy (079.C-0127/F)). Table 2 is only available in electronic form at http://www.aanda.org

  2. Ro-vibrational Stark effect on H2 and D2 molecules adsorbed in NaA zeolite

    NASA Astrophysics Data System (ADS)

    Bras, N.

    1999-03-01

    In order to explain the induced infrared bands of H2 and D2 adsorbed in NaA zeolites the Stark effect on the ro-vibrational levels of these molecules is considered for electric fields created by various charge distributions. The shift and intensity of the induced ro-vibration transitions are calculated.

  3. Establishment of rock bream Oplegnathus fasciatus embryo (RoBE-4) cells with cytolytic infection of red seabream iridovirus (RSIV).

    PubMed

    Oh, So-Young; Nishizawa, Toyohiko

    2016-12-01

    Red seabream iridovirus (RSIV) is a member of genus Megalocytivirus in the family Iridoviridae. RSIV infection causes significant economic losses of marine-fishes in East Asian countries. Grunt fin (GF) cell line has been commonly used for culturing RSIV. However, it is not suitable for definite evaluation of infectivity titer of RSIV because cells infected with RSIV are not completely cytolysed. Thus, we established a new cell line, RoBE-4, from rock bream (Oplegnathus fasciatus) eyed-egg embryos in this study. Morphologically, RoBE-4 cells were fibroblastic-like. They have been stably grown over two-years with 60 passages using Leibovitz's L-15 medium containing 10% (v/v) fetal bovine serum. RoBE-4 cells infected with RSIV exhibited cytopathic effects (CPE) with cell rounding. They were cytolysed completely after ≥2 weeks of culture. Numerous RSIV particles with icosahedral morphology of approximately 122nm in diameter were observed in cytoplasmic area of infected RoBE-4 cells. The RSIV-suceptibility and amount of extracellular RSIV released by RoBE-4 cells were 100-fold higher than those by GF cells. RSIV cultured with RoBE-4 cells was highly virulent to rock bream in infection experiments. Therefore, using RoBE-4 cells instead of GF cells will enable accurate and sensitive measurement of RSIV infectivity. In addition, RoBE-4 cells might be used to produce RSIV vaccine in the future with significant reduction in cost.

  4. Molecular cloning, expression, and chromosome 19 localization of a human Ro/SS-A autoantigen.

    PubMed Central

    McCauliffe, D P; Lux, F A; Lieu, T S; Sanz, I; Hanke, J; Newkirk, M M; Bachinski, L L; Itoh, Y; Siciliano, M J; Reichlin, M

    1990-01-01

    Ro/SS-A antibodies are found in a number of human autoimmune disorders including Sjogren's syndrome and several systemic lupus erythematosus-related disorders. These heterogeneous autoantibodies are known to recognize several distinct cellular antigens. With synthetic oligonucleotides corresponding to amino acid sequence information we have isolated a full-length cDNA clone which encodes a human Ro ribonucleoprotein autoantigen. The 1,890-base pair clone contains an open reading frame that encodes a 417-amino acid, 48-kD polypeptide that migrates aberrantly at 60 kD by SDS-PAGE. Rabbit antibodies raised against this protein's recently described amino-terminal epitope react with a previously identified 52-kD human Ro protein and immunoprecipitate the human cytoplasmic RNAs. Ultraviolet light cross-linking studies suggest that this Ro protein binds each of the four major human cytoplasmic RNAs. The deduced amino acid sequence is 63% homologous to an Onchocerca volvulus antigen. Southern filter hybridization analysis indicates that this gene is not highly polymorphic and exists as a single copy in the human genome. Chromosomal localization studies place this gene on the short arm of chromosome 19 near the gene encoding the low density lipoprotein receptor. Images PMID:2332496

  5. RO filtration of biologically treated textile and dyeing effluents using ozonation as a pre-treatment.

    PubMed

    Wang, H Y; Guan, Y T; Mizuno, T; Tsuno, H

    2010-01-01

    Bench-scale experiments were conducted to investigate the application of ozonation pre-treatment for biologically treated textile and dyeing wastewater to improve performance of the RO process. Based on ozonation experiments, four specific ozone consumptions (SOC), 0, 0.3, 0.6, 4.0 mg O₃/mg DOC₀ were chosen for study of the effects of ozonation on the reverse osmosis (RO) process. Membrane flux was recorded. Also, the permeate water quality parameters such as TOC, conductivity were analyzed. In addition, fouled membrane cleaning was studied. The study further examined the nature and mechanisms of membrane fouling using scanning electron microscopy (SEM) and the energy dispersive X-ray spectrometer (EDS). The effect of ozonation on RO filtration was found to depend on SOC. The study revealed that significant improvement can be achieved in the efficiency of RO filtration by employing ozonation with 0.6 mg O₃/mg DOC₀ SOC. Although the product water purity slightly decreased, the ozonation pre-treatment showed advantages at 0.6 mg O₃/mg DOC₀ SOC for the following: (i) mitigation of flux decline due to membrane fouling; (ii) improvement in foulants cleanability. In addition, hypotheses were put forward to explain the reasons from the aspect of organic matter characteristics changed by ozonation, such as changing on functional groups and molecular weight of organic matter.

  6. Uncovering the planets and stellar activity of CoRoT-7 using only radial velocities

    NASA Astrophysics Data System (ADS)

    Faria, J. P.; Haywood, R. D.; Brewer, B. J.; Figueira, P.; Oshagh, M.; Santerne, A.; Santos, N. C.

    2016-04-01

    Stellar activity can induce signals in the radial velocities of stars, complicating the detection of orbiting low-mass planets. We present a method to determine the number of planetary signals present in radial-velocity datasets of active stars, using only radial-velocity observations. Instead of considering separate fits with different number of planets, we use a birth-death Markov chain Monte Carlo algorithm to infer the posterior distribution for the number of planets in a single run. In a natural way, the marginal distributions for the orbital parameters of all planets are also inferred. This method is applied to HARPS data of CoRoT-7. We confidently recover the orbits of both CoRoT-7b and CoRoT-7c although the data show evidence for the presence of additional signals. All data and software presented in this article are available online at http://https://github.com/j-faria/exoBD-CoRoT7

  7. Draft Genome Sequence of the Xylella fastidiosa CoDiRO Strain

    PubMed Central

    Chiumenti, Michela; Saponari, Maria; Donvito, Giacinto; Italiano, Alessandro; Loconsole, Giuliana; Boscia, Donato; Cariddi, Corrado; Martelli, Giovanni Paolo; Saldarelli, Pasquale

    2015-01-01

    We determined the draft genome sequence of the Xylella fastidiosa CoDiRO strain, which has been isolated from olive plants in southern Italy (Apulia). It is associated with olive quick decline syndrome (OQDS) and characterized by extensive scorching and desiccation of leaves and twigs. PMID:25676759

  8. RoMPS concept review automatic control of space robot, volume 2

    NASA Technical Reports Server (NTRS)

    Dobbs, M. E.

    1991-01-01

    Topics related to robot operated materials processing in space (RoMPS) are presented in view graph form and include: (1) system concept; (2) Hitchhiker Interface Requirements; (3) robot axis control concepts; (4) Autonomous Experiment Management System; (5) Zymate Robot Controller; (6) Southwest SC-4 Computer; (7) oven control housekeeping data; and (8) power distribution.

  9. Possible role of anti-SSA/Ro antibodies in the pathogenesis of pulmonary hypertension

    PubMed Central

    Guerreso, Kelsey; Conner, Edward Alexander

    2016-01-01

    Introduction There are many different causes of pulmonary hypertension and the pathogenesis of the disease is still being elucidated. Although they are not the most common, autoimmunity and inflammation have been identified as possible causes. No one autoantibody has been identified as the definite cause of pulmonary hypertension. We present a rare association of anti-SSA/Ro antibodies and isolated pulmonary hypertension. Case presentation A 53 year old African American female presented with abdominal pain, nausea, weight loss, dyspnea and fatigue. Upon further exam she was found to have high titers of antinuclear antibodies and anti-SSA/Ro antibodies. This antibody profile would typically be suggestive of Sjögren's Syndrome, which is characterized by dry eyes and poor salivary gland function. However, since this patient did not have any symptoms consistent with the disease a diagnosis of Sjögren's Syndrome could not be made. A combination of laboratory, imaging and diagnostic studies were done that revealed a final diagnosis of pulmonary hypertension. Conclusion It is known that pulmonary hypertension has association with autoimmune diseases, however no clear markers yet exist. Anti-SSA/Ro antibodies have been rarely described in cases of pulmonary disease, and less so in pulmonary hypertension. This case describes a unique association between isolated pulmonary hypertension and anti-SSA/Ro antibody, thereby illustrating the need to investigate this autoantibody and others in the pathogenesis of autoimmune pulmonary hypertension. PMID:27222785

  10. CoRoT-2a Magnetic Activity: Hints for Possible Star-Planet Interaction

    NASA Astrophysics Data System (ADS)

    Pagano, Isabella; Lanza, Antonino F.; Leto, Giuseppe; Messina, Sergio; Barge, Pierre; Baglin, Annie

    2009-09-01

    CoRoT-2a is a young (≈0.5 Gyr) G7V star accompanied by a transiting hot-Jupiter, discovered by the CoRoT satellite (Alonso et al. Astron Astrophys 482:L21, 2008; Bouchy et al. Astron Astrophys 482:L25, 2008). An analysis of its photospheric activity, based on spot modelling techniques previously developed by our group for the analysis of the Sun as a star, shows that the active regions on CoRoT-2a arised within two active longitudes separated by about 180° and rotating with periods of 4.5221 and 4.5543 days, respectively, at epoch of CoRoT observations (112 continous days centered at ≈2007.6). We show that the total spotted area oscillates with a period of about 28.9 days, a value close to 10 times the synodic period of the planet with respect to the active longitude pattern rotating in 4.5221 days. Moreover, the variance of the stellar flux is modulated in phase with the planet orbital period. This suggests a possible star-planet magnetic interaction, a phenomenon already seen in other extrasolar planetary systems hosting hot-Jupiters.

  11. Jean Vigo's "Zéro De Conduite" and the Spaces of Revolt

    ERIC Educational Resources Information Center

    Vanobbergen, Bruno; Grosvenor, Ian; Simon, Frank

    2014-01-01

    In this article we will contribute to the contemporary theoretical debate about film by considering, from a history-of-education perspective, the film "Zéro de conduite" by Jean Vigo (1905--1934). This film is classified under the umbrella of "poetic realism": a product of "cinéma de gauche" and an avant-gardist,…

  12. Variation in Herrnstein's ro as a function of alternative reinforcement rate

    PubMed Central

    Dougan, James D.; McSweeney, Frances K.

    1985-01-01

    In a test of Herrnstein's (1970, 1974) equation for simple schedules, 15 pigeons pecked a key that produced food delivered according to variable-interval schedules. One group of birds was water deprived, and food-reinforced key pecking occurred in the presence of free water. Two other groups were not water deprived; water was present for one and absent for the other. As predicted by Herrnstein, the parameter ro was significantly higher in the water-deprived group than in the two nondeprived groups. Contrary to Herrnstein's interpretation of ro, the rate of drinking varied across schedules. Herrnstein's interpretation can be salvaged by considering ro to be an average. However, if ro is an average, the equation is not a good explanation of behavior because this average is not valid until all schedules have been sampled. In addition, low percentages of variance accounted for suggest that Herrnstein's equation may be of limited usefulness even as a descriptive model for these situations. PMID:16812413

  13. Spectral characterization and differential rotation study of active CoRoT stars

    NASA Astrophysics Data System (ADS)

    Nagel, E.; Czesla, S.; Schmitt, J. H. M. M.

    2016-05-01

    The CoRoT space telescope observed nearly 160 000 light curves. Among the most outstanding is that of the young, active planet host star CoRoT-2A. In addition to deep planetary transits, the light curve of CoRoT-2A shows strong rotational variability and a superimposed beating pattern. To study the stars that produce such an intriguing pattern of photometric variability, we identified a sample of eight stars with rotation periods between 0.8 and 11 days and photometric variability amplitudes of up to 7.5%, showing a similar CoRoT light curve. We also obtained high-resolution follow-up spectroscopy with TNG/SARG and carried out a spectral analysis with SME and MOOG. We find that the color dependence of the light curves is consistent with rotational modulation due to starspots and that latitudinal differential rotation provides a viable explanation for the light curves, although starspot evolution is also expected to play an important role. Our MOOG and SME spectral analyses provide consistent results, showing that the targets are dwarf stars with spectral types between F and mid-K. Detectable Li i absorption in four of the targets confirms a low age of 100-400 Myr also deduced from gyrochronology. Our study indicates that the photometric beating phenomenon is likely attributable to differential rotation in fast-rotating stars with outer convection zones.

  14. A New Method for Detecting and Monitoring Atmospheric Natural Hazards with GPS RO

    NASA Astrophysics Data System (ADS)

    Biondi, R.; Steiner, A. K.; Rieckh, T. M.; Kirchengast, G.

    2014-12-01

    Global Positioning System (GPS) Radio Occultation (RO) allows measurements in any meteorological condition, with global coverage, high vertical resolution, and high accuracy. With more than 13 years of data availability, RO also became a fundamental tool for studying climate change. We present here the application of RO for detecting and monitoring tropical cyclones (TCs), deep convective systems (CSs) and volcanic ash clouds (ACs).Deep CSs and TCs play a fundamental role in atmospheric circulation producing vertical transport, redistributing water vapor and trace gases, changing the thermal structure of the Upper Troposphere and Lower Stratosphere (UTLS) and affecting climate through overshooting into the stratosphere. Explosive volcanic eruptions produce large ACs dangerous for the aviation and they can impact climate when the ash is injected into the UTLS.The detection of cloud top height, the determination of cloud extent, the discrimination of ACs from CSs clouds and the detection of overshooting are main challenges for atmospheric natural hazards study. We created a reference atmosphere with a resolution of 5° in latitude and longitude, sampled on a 1° x 1° grid, and a vertical sampling of 100 m. We then compared RO profiles acquired during TCs, CSs and ACs to the reference atmosphere and computed anomaly profiles.CSs, TCs and the ACs leave a clear signature in the atmosphere which can be detected by RO. Using RO temperature and bending angle profiles we gain insight into the vertical thermal structure and developed a new method for detecting the cloud top altitude with high accuracy.We have characterized the TCs by ocean basins and intensities, showing that they have a different thermal structure and reach to different altitudes according to the basin. We provide statistics on overshooting frequency, achieving results consistent with patterns found in the literature and demonstrating that RO is well suited for this kind of study. We have analyzed the

  15. Autophagy inhibitors.

    PubMed

    Pasquier, Benoit

    2016-03-01

    Autophagy is a lysosome-dependent mechanism of intracellular degradation. The cellular and molecular mechanisms underlying this process are highly complex and involve multiple proteins, including the kinases ULK1 and Vps34. The main function of autophagy is the maintenance of cell survival when modifications occur in the cellular environment. During the past decade, extensive studies have greatly improved our knowledge and autophagy has exploded as a research field. This process is now widely implicated in pathophysiological processes such as cancer, metabolic, and neurodegenerative disorders, making it an attractive target for drug discovery. In this review, we will summarize the different types of inhibitors that affect the autophagy machinery and provide some potential therapeutic perspectives.

  16. Binding of antibodies to the extractable nuclear antigens SS-A/Ro and SS-B/La is induced on the surface of human keratinocytes by ultraviolet light (UVL): Implications for the pathogenesis of photosensitive cutaneous lupus

    SciTech Connect

    Furukawa, F.; Kashihara-Sawami, M.; Lyons, M.B.; Norris, D.A. )

    1990-01-01

    Autoantibodies to the non-histone nucleoprotein antigens SS-A/Ro, SS-B/La, and RNP are highly associated with photosensitive cutaneous lupus erythematosus (LE). In order to better understand the potential mechanisms of ultraviolet (UV) light on photosensitivity in patients with cutaneous LE, we designed immunopathologic in vitro and in vivo experiments to evaluate the effects of UV on the binding of such autoantibodies to the surface of human keratinocytes, one major target of immunologic damage in photosensitive LE. Short-term 2% paraformaldehyde fixation of suspensions of cultured human keratinocytes previously incubated with monospecific antiserum probes enabled the detection of ENA expression on the cell surface by flow-cytometry analysis. UVB light (280-320 nm) induced the binding of monospecific antibody probes for SS-A/Ro and SS-B/La on keratinocytes in a dose-dependent pattern with maximal induction observed at the dose of 200 mJ/cm2 UVB. Binding of SS-A/Ro, SS-B/La, and RNP antibody was augmented strongly, but binding of anti-Sm was very weak. In contrast, UVA (320-400 nm) light had no effect on the induction of binding of these antibody probes. Identical results were seen by standard immunofluorescence techniques. Hydroxyurea-treated keratinocytes showed similar induction of those antigens by UVB irradiation, which suggested that ENA expression on cultured keratinocytes by UVB were cell-cycle independent. Tunicamycin, an inhibitor of glycosylation of proteins, reduced UVB light effect on the SS-A/Ro and SS-B/La antigen's expression. These in vitro FACS analyses revealed that ENA augmentation on the keratinocyte cell surface was dose dependent, UVB dependent, glycosylation dependent, and cell-cycle independent. In vivo ENA augmentation on the keratinocyte surface was examined in suction blister epidermal roofs.

  17. Expression of the Memory Marker CD45RO on Helper T Cells in Macaques

    PubMed Central

    Valentine, Michael; Song, Kejing; Maresh, Grace A.; Mack, Heather; Huaman, Maria Cecilia; Polacino, Patricia; Ho, On; Cristillo, Anthony; Kyung Chung, Hye; Hu, Shiu-Lok; Pincus, Seth H.

    2013-01-01

    Background In humans it has been reported that a major site of the latent reservoir of HIV is within CD4+ T cells expressing the memory marker CD45RO, defined by the mAb UCHL1. There are conflicting reports regarding the expression of this antigen in macaques, the most relevant animal species for studying HIV pathogenesis and testing new therapies. There is now a major effort to eradicate HIV reservoirs and cure the infection. One approach is to eliminate subsets of cells housing the latent reservoir, using UCHL1 to target these cells. So that such studies may be performed in macaques, it is essential to determine expression of CD45RO. Methods We have used immunofluorescence and flow cytometry to study cell surface expression of CD45RO on lymphocytes from PBMC, lymphoid, and GI organs of rhesus, pigtailed, and cynomolgus macaques. Both direct and indirect immunofluorescence experiments were performed. Findings CD45RO is expressed on a subset of CD4+ lymphocytes of all pigtailed, a fraction of rhesus, and neither of the cynomolgus macaques studied. The binding of UCHL1 to macaque cells was of lower avidity than to human cells. This could be overcome by forming UCHL1 multimers. Directly conjugating fluors to UCHL1 can inhibit UCHL1 binding to macaque cells. Patterns of UCHL1 expression differ somewhat in macaques and humans, and from that of other memory markers often used in macaques. Conclusions CD45RO, defined with mAb UCHL1, is well expressed on CD4+ cells in pigtailed macaques. Using tissues recovered from latently infected pigtailed macaques we are determining whether UCHL1, or other memory markers, can define the cellular locus of the reservoir. The low avidity of this interaction could limit the utility of UCHL1, in its conventional form, to eliminate cells in vivo and test this approach in macaque models of HIV infection. PMID:24023920

  18. Transiting exoplanets from the CoRoT space mission . XIX. CoRoT-23b: a dense hot Jupiter on an eccentric orbit

    NASA Astrophysics Data System (ADS)

    Rouan, D.; Parviainen, H.; Moutou, C.; Deleuil, M.; Fridlund, M.; Ofir, A.; Havel, M.; Aigrain, S.; Alonso, R.; Auvergne, M.; Baglin, A.; Barge, P.; Bonomo, A. S.; Bordé, P.; Bouchy, F.; Cabrera, J.; Cavarroc, C.; Csizmadia, Sz.; Deeg, H. J.; Diaz, R. F.; Dvorak, R.; Erikson, A.; Ferraz-Mello, S.; Gandolfi, D.; Gillon, M.; Guillot, T.; Hatzes, A.; Hébrard, G.; Jorda, L.; Léger, A.; Llebaria, A.; Lammer, H.; Lovis, C.; Mazeh, T.; Ollivier, M.; Pätzold, M.; Queloz, D.; Rauer, H.; Samuel, B.; Santerne, A.; Schneider, J.; Tingley, B.; Wuchterl, G.

    2012-01-01

    We report the detection of CoRoT-23b, a hot Jupiter transiting in front of its host star with a period of 3.6314 ± 0.0001 days. This planet was discovered thanks to photometric data secured with the CoRoT satellite, combined with spectroscopic radial velocity (RV) measurements. A photometric search for possible background eclipsing binaries conducted at CFHT and OGS concluded with a very low risk of false positives. The usual techniques of combining RV and transit data simultaneously were used to derive stellar and planetary parameters. The planet has a mass of Mp = 2.8 ± 0.3 MJup, a radius of Rpl= 1.05 ± 0.13RJup, a density of ≈ 3 g cm-3. RV data also clearly reveal a nonzero eccentricity of e = 0.16 ± 0.02. The planet orbits a mature G0 main sequence star of V = 15.5 mag, with a mass M⋆ = 1.14 ± 0.08 M⊙, a radius R ⋆ = 1. 61 ± 0.18 R⊙ and quasi-solarabundances. The age of the system is evaluated to be 7 Gyr, not far from the transition to subgiant, in agreement with the rather large stellar radius. The two features of a significant eccentricity of the orbit and of a fairly high density are fairly uncommon for a hot Jupiter. The high density is, however, consistent with a model of contraction of a planet at this mass, given the age of the system. On the other hand, at such an age, circularization is expected to be completed. In fact, we show that for this planetary mass and orbital distance, any initial eccentricity should not totally vanish after 7 Gyr, as long as the tidal quality factor Qp is more than a few 105, a value that is the lower bound of the usually expected range. Even if CoRoT-23b features a density and an eccentricity that are atypical of a hot Jupiter, it is thus not an enigmatic object. The CoRoT space mission, launched on 27 December 2006, has been developed and is operated by CNES, with the contribution of Austria, Belgium, Brazil, ESA, Germany, and Spain. First CoRoT data are available to the public from the CoRoT archive: http

  19. The autoantigen Ro52 is an E3 ligase resident in the cytoplasm but enters the nucleus upon cellular exposure to nitric oxide

    SciTech Connect

    Espinosa, Alexander; Oke, Vilija; Elfving, Ase; Nyberg, Filippa; Covacu, Ruxandra; Wahren-Herlenius, Marie

    2008-12-10

    Patients with the systemic autoimmune diseases Sjoegrens's syndrome and systemic lupus erythematosus often have autoantibodies against the intracellular protein Ro52. Ro52 is an E3 ligase dependent on the ubiquitin conjugation enzymes UBE2D1 and UBE2E1. While Ro52 and UBE2D1 are cytoplasmic proteins, UBE2E1 is localized to the nucleus. Here, we investigate how domains of human Ro52 regulate its intracellular localization. By expressing fluorescently labeled Ro52 and Ro52 mutants in HeLa cells, an intact coiled-coil domain was found to be necessary for the cytoplasmic localization of Ro52. The amino acids 381-470 of the B30.2 region were essential for translocation into the nucleus. Furthermore, after exposure of HeLa cells to the inflammatory mediator nitric oxide (NO), Ro52 translocated to the nucleus. A nuclear localization of Ro52 in inflamed tissue expressing inducible NO synthetase (iNOS) from cutaneous lupus patients was observed by immunohistochemistry and verified in NO-treated cultures of patient-derived primary keratinocytes. Our results show that the localization of Ro52 is regulated by endogenous sequences, and that nuclear translocation is induced by an inflammatory mediator. This suggests that Ro52 has both cytoplasmic and nuclear substrates, and that Ro52 mediates ubiquitination through UBE2D1 in the cytoplasm and through UBE2E1 in the nucleus.

  20. Gamma-Secretase/Notch Signalling Pathway Inhibitor RO4929097 and Temsirolimus in Treating Patients With Advanced Solid Tumors

    ClinicalTrials.gov

    2014-05-29

    Endometrial Papillary Serous Carcinoma; Recurrent Endometrial Carcinoma; Recurrent Renal Cell Cancer; Stage III Endometrial Carcinoma; Stage III Renal Cell Cancer; Stage IV Endometrial Carcinoma; Stage IV Renal Cell Cancer; Unspecified Adult Solid Tumor, Protocol Specific

  1. Vismodegib and Gamma-Secretase/Notch Signalling Pathway Inhibitor RO4929097 in Treating Patients With Advanced or Metastatic Sarcoma

    ClinicalTrials.gov

    2016-06-09

    Adult Alveolar Soft Part Sarcoma; Adult Angiosarcoma; Adult Desmoplastic Small Round Cell Tumor; Adult Epithelioid Hemangioendothelioma; Adult Epithelioid Sarcoma; Adult Extraskeletal Myxoid Chondrosarcoma; Adult Extraskeletal Osteosarcoma; Adult Fibrosarcoma; Adult Leiomyosarcoma; Adult Liposarcoma; Adult Malignant Mesenchymoma; Adult Malignant Peripheral Nerve Sheath Tumor; Adult Rhabdomyosarcoma; Adult Synovial Sarcoma; Adult Unclassified Pleomorphic Sarcoma; Chondrosarcoma; Clear Cell Sarcoma of the Kidney; Conjunctival Kaposi Sarcoma; Dermatofibrosarcoma Protuberans; Gastrointestinal Stromal Tumor; Metastatic Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor; Metastatic Osteosarcoma; Ovarian Sarcoma; Recurrent Adult Soft Tissue Sarcoma; Recurrent Adult Unclassified Pleomorphic Sarcoma of Bone; Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor; Recurrent Kaposi Sarcoma; Recurrent Osteosarcoma; Recurrent Uterine Corpus Sarcoma; Small Intestine Leiomyosarcoma; Stage III Adult Soft Tissue Sarcoma; Stage III Uterine Sarcoma; Stage IV Adult Soft Tissue Sarcoma; Stage IV Uterine Sarcoma; Unclassified Pleomorphic Sarcoma of Bone

  2. Transiting exoplanets from the CoRoT space mission. XVII. The hot Jupiter CoRoT-17b: a very old planet

    NASA Astrophysics Data System (ADS)

    Csizmadia, Sz.; Moutou, C.; Deleuil, M.; Cabrera, J.; Fridlund, M.; Gandolfi, D.; Aigrain, S.; Alonso, R.; Almenara, J.-M.; Auvergne, M.; Baglin, A.; Barge, P.; Bonomo, A. S.; Bordé, P.; Bouchy, F.; Bruntt, H.; Carone, L.; Carpano, S.; Cavarroc, C.; Cochran, W.; Deeg, H. J.; Díaz, R. F.; Dvorak, R.; Endl, M.; Erikson, A.; Ferraz-Mello, S.; Fruth, Th.; Gazzano, J.-C.; Gillon, M.; Guenther, E. W.; Guillot, T.; Hatzes, A.; Havel, M.; Hébrard, G.; Jehin, E.; Jorda, L.; Léger, A.; Llebaria, A.; Lammer, H.; Lovis, C.; MacQueen, P. J.; Mazeh, T.; Ollivier, M.; Pätzold, M.; Queloz, D.; Rauer, H.; Rouan, D.; Santerne, A.; Schneider, J.; Tingley, B.; Titz-Weider, R.; Wuchterl, G.

    2011-07-01

    We report on the discovery of a hot Jupiter-type exoplanet, CoRoT-17b, detected by the CoRoT satellite. It has a mass of 2.43 ± 0.30 MJup and a radius of 1.02 ± 0.07 RJup, while its mean density is 2.82 ± 0.38 g/cm3. CoRoT-17b is in a circular orbit with a period of 3.7681 ± 0.0003 days. The host star is an old (10.7 ± 1.0 Gyr) main-sequence star, which makes it an intriguing object for planetary evolution studies. The planet's internal composition is not well constrained and can range from pure H/He to one that can contain ~380 earth masses of heavier elements. The CoRoT space mission, launched on December 27th 2006, has been developed and is operated by CNES, with the contribution of Austria, Belgium, Brazil, ESA (RSSD and Science Programme), Germany and Spain. Part of the observations were obtained at the Canada-France-Hawaii Telescope (CFHT) which is operated by the National Research Council of Canada, the Institut National des Sciences de l'Univers of the Centre National de la Recherche Scientifique of France, and the University of Hawaii. Based on observations made with HARPS spectrograph on the 3.6-m European Organisation for Astronomical Research in the Southern Hemisphere telescope at La Silla Observatory, Chile (ESO program 184.C-0639). Based on observations made with the IAC80 telescope operated on the island of Tenerife by the Instituto de Astrofísica de Canarias in the Spanish Observatorio del Teide. Part of the data presented herein were obtained at the W.M. Keck Observatory, which is operated as a scientific partnership among the California Institute of Technology, the University of California and the National Aeronautics and Space Administration. The Observatory was made possible by the generous financial support of the W.M. Keck Foundation.

  3. Chronic ethanol administration increases the binding of sup 3 H Ro-15-4513 in primary cultured spinal cord neurons

    SciTech Connect

    Mlatre, M.; Ticku, M.K. )

    1989-02-09

    Ro 15-4513 (ethyl-8-azido-5, 6-dihydro-5-methyl-6-oxo-4H-imidazo (1,5{alpha}), (1,4) benzodiazepine-3-carboxylate) is reported to be a selective ethanol antagonist in biochemical and behavioral studies. The effect of chronic ethanol treatment on the binding of ({sup 3}H)Ro 15-4513 was investigated in cultured spinal cord neurons, which are shown to possess all the elements of GABA benzodiazepine receptor complex. Chronic ethanol treatment (50 mM for 6 hr, 12 hr, 18 hr, 3 days, and 5{sub 3} days) produced an increase in the specific binding of ({sub 3}H)Ro 15-4513. The increase in binding in these neurons was due to an increase in the number (B{sub max}) of receptor sites. This effect was specific for Ro 15-4513, since identical ethanol treatment did not alter the binding of benzodiazepine antagonist ({sup 3}H)Ro 15-1788 or agonist ({sup 3}H)flunitrazepam or inverse agonist ({sup 3}H)methyl-{beta}-carboline-3-carboxylate. Similar results have been reported following chronic ethanol treatment to rats. These results suggest that the Ro 15-4513 binding sites on the oligomeric GABA receptor complex are altered following chronic ethanol administration, and support the notion of a unique role of Ro 15-4513 as an ethanol antagonist.

  4. Characterization of the Discriminative Stimulus Effects of a NOP Receptor Agonist Ro 64-6198 in Rhesus Monkeys

    PubMed Central

    Zelenock, Kathy A.; Lindsey, Angela M.; Sulima, Agnieszka; Rice, Kenner C.; Prinssen, Eric P.; Wichmann, Jürgen; Woods, James H.

    2016-01-01

    Nociceptin/orphanin FQ receptor (NOP) agonists have been reported to produce antinociceptive effects in rhesus monkeys with comparable efficacy to μ-opioid receptor (MOP) agonists, but without their limiting side effects. There are also known to be species differences between rodents and nonhuman primates (NHPs) in the behavioral effects of NOP agonists. The aims of this study were the following: 1) to determine if the NOP agonist Ro 64-6198 could be trained as a discriminative stimulus; 2) to evaluate its pharmacological selectivity as a discriminative stimulus; and 3) to establish the order of potency with which Ro 64-6198 produces discriminative stimulus effects compared with analgesic effects in NHPs. Two groups of rhesus monkeys were trained to discriminate either fentanyl or Ro 64-6198 from vehicle. Four monkeys were trained in the warm-water tail-withdrawal procedure to measure antinociception. Ro 64-6198 produced discriminative stimulus effects that were blocked by the NOP antagonist J-113397 and not by naltrexone. The discriminative stimulus effects of Ro 64-6198 partially generalized to diazepam, but not to fentanyl, SNC 80, ketocyclazocine, buprenorphine, phencyclidine, or chlorpromazine. Fentanyl produced stimulus effects that were blocked by naltrexone and not by J-113397, and Ro 64-6198 did not produce fentanyl-appropriate responding in fentanyl-trained animals. In measures of antinociception, fentanyl, but not Ro 64-6198, produced dose-dependent increases in tail-withdrawal latency. Together, these results demonstrate that Ro 64-6198 produced stimulus effects in monkeys that are distinct from other opioid receptor agonists, but may be somewhat similar to diazepam. In contrast to previous findings, Ro 64-6198 did not produce antinociception in the majority of animals tested even at doses considerably greater than those that produced discriminative stimulus effects. PMID:26801398

  5. Improved variability classification of CoRoT targets with Giraffe spectra

    NASA Astrophysics Data System (ADS)

    Sarro, L. M.; Debosscher, J.; Neiner, C.; Bello-García, A.; González-Marcos, A.; Prendes-Gero, B.; Ordieres, J.; León, G.; Aerts, C.; de Batz, B.

    2013-02-01

    Aims: We present an improved method for automated stellar variability classification, using fundamental parameters derived from high resolution spectra, with the goal to improve the variability classification obtained using information derived from CoRoT light curves only. Although we focus on Giraffe spectra and CoRoT light curves in this work, the methods are much more widely applicable. Methods: In order to improve the variability classification obtained from the photometric time series, only rough estimates of the stellar physical parameters (Teff and log (g)) are needed because most variability types that overlap in the space of time series parameters, are well separated in the space of physical parameters (e.g. γ Dor/SPB or δ Sct/β Cep). In this work, several state-of-the-art machine learning techniques are combined to estimate these fundamental parameters from high resolution Giraffe spectra. Next, these parameters are used in a multi-stage Gaussian-Mixture classifier to perform an improved supervised variability classification of CoRoT light curves. The variability classifier can be used independently of the regression module that estimates the physical parameters, so that non-spectroscopic estimates derived e.g. from photometric colour indices can be used instead. Results: Teff and log (g) are derived from Giraffe spectra, for 6832 CoRoT targets. The use of those parameters in addition to information extracted from the CoRoT light curves, significantly improves the results of our previous automated stellar variability classification. Several new pulsating stars are identified with high confidence levels, including hot pulsators such as SPB and β Cep, and several γ Dor-δ Sct hybrids. From our samples of new γ Dor and δ Sct stars, we find strong indications that the instability domains for both types of pulsators are larger than previously thought. The CoRoT space mission, launched on 27 December 2006, has been developed and is operated by CNES, with

  6. Photometric variability of the Be star CoRoT-ID 102761769

    NASA Astrophysics Data System (ADS)

    Emilio, M.; Andrade, L.; Janot-Pacheco, E.; Baglin, A.; Gutiérrez-Soto, J.; Suárez, J. C.; de Batz, B.; Diago, P.; Fabregat, J.; Floquet, M.; Frémat, Y.; Huat, A. L.; Hubert, A. M.; Espinosa Lara, F.; Leroy, B.; Martayan, C.; Neiner, C.; Semaan, T.; Suso, J.

    2010-11-01

    Context. Classical Be stars are rapid rotators of spectral type late O to early A and luminosity class V-III, which exhibit Balmer emission lines and often a near infrared excess originating in an equatorially concentrated circumstellar envelope, both produced by sporadic mass ejection episodes. The causes of the abnormal mass loss (the so-called Be phenomenon) are as yet unknown. Aims: For the first time, we can now study in detail Be stars outside the Earth's atmosphere with sufficient temporal resolution. We investigate the variability of the Be Star CoRoT-ID 102761769 observed with the CoRoT satellite in the exoplanet field during the initial run. Methods: One low-resolution spectrum of the star was obtained with the INT telescope at the Observatorio del Roque de los Muchachos. A time series analysis was performed using both cleanest and singular spectrum analysis algorithms to the CoRoT light curve. To identify the pulsation modes of the observed frequencies, we computed a set of models representative of CoRoT-ID 102761769 by varying its main physical parameters inside the uncertainties discussed. Results: We found two close frequencies related to the star. They are 2.465 c d-1 (28.5 μHz) and 2.441 c d-1 (28.2 μHz). The precision to which those frequencies were found is 0.018 c d-1 (0.2 μHz). The projected stellar rotation was estimated to be 120 km s-1 from the Fourier transform of spectral lines. If CoRoT-ID 102761769 is a typical Galactic Be star it rotates near the critical velocity. The critical rotation frequency of a typical B5-6 star is about 3.5 c d-1 (40.5 μHz), which implies that the above frequencies are really caused by stellar pulsations rather than star's rotation. The CoRoT space mission was developed and is operated by the French space agency CNES, with participation of ESA's RSSD and Science Programmes, Austria, Belgium, Brazil, Germany, and Spain.

  7. PCR amplification of RoTat 1.2 VSG gene in Trypanosoma evansi isolates in Kenya.

    PubMed

    Ngaira, J M; Njagi, E N M; Ngeranwa, J J N; Olembo, N K

    2004-02-26

    A direct card agglutination test for Trypanosoma evansi, CATT/T. evansi based on the predominant variable antigen-type (pVAT) RoTat 1.2 was evaluated previously in the field in Isiolo District, Kenya. Sixteen out of 51 (31.4%) parasitologically positive camels were negative by the antibody detection test. In the present study, trypanosomes isolated from the camels were analysed in an attempt to determine the cause of the false negative results of CATT/T. evansi. A total of 20 field isolates comprised 16 stocks from camels that were negative by CATT/T. evansi, and 4 from CATT/T. evansi-positive camels. In addition, 15 known T. evansi and four T. brucei were used as reference. Purified DNA samples were tested using an established RoTat 1.2-based polymerase chain reaction (PCR) that yields a 488 bp product for the specific detection of T. evansi. Antibodies to RoTat 1.2 variant surface glycoprotein (VSG) were used in Western blotting to detect RoTat 1.2 VSG linear epitopes. Results of PCR and Western blot showed that the 16 stocks isolated from CATT/T. evansi-negative camels fell into three groups. In Group 1, both the RoTat 1.2 VSG gene and the VSG were absent in three stocks. In five trypanosome stocks in Group 2, the RoTat 1.2 VSG gene was detected, but Western blot was negative indicating absence of the expressed VSG. Five other stocks containing the RoTat 1.2 VSG gene were also in this group. The RoTat 1.2 VSG gene was detected and Western blot was positive in all four trypanosome stocks in Group 3. All four stocks from CATT/T. evansi-positive camels contained the RoTat 1.2 VSG gene and the expressed VSG. The reference T. evansi KETRI 2479 lacked the RoTat 1.2 VSG gene and there was no immune reactivity detected by Western blot. The rest of the reference T. evansi stocks examined contained the RoTat 1.2 VSG gene. All the four T. brucei samples examined were negative by PCR and Western blot. In conclusion, this study showed that the RoTat 1.2 VSG gene was absent

  8. Effect of an imidazobenzodiazepine, Ro15-4513, on the incoordination and hypothermia produced by ethanol and pentobarbital

    SciTech Connect

    Hoffman, P.L.; Tabakoff, B.; Szabo, G.; Suzdak, P.D.; Paul, S.M.

    1987-08-03

    The imidazobenzodiazepine, Ro15-4513, which is a partial inverse agonist at brain benzodiazepine receptors, reversed the incoordinating effect of ethanol in mice, as measured on an accelerating Rotarod. This effect was blocked by benzodiazepine receptor antagonists. In contrast, Ro15-4513 had no effect on ethanol-induced hypothermia in mice. However, Ro15-4513 reversed the hypothermic effect of pentobarbital, and, at higher dose, also reversed the incoordinating effect of pentobarbital in mice. The data support the hypothesis that certain of the pharmacological effects of ethanol are mediated by actions at the GABA-benzodiazepine receptor-coupled chloride channel. 35 references, 2 figures.

  9. Understanding nuclear motions in molecules: Derivation of Eckart frame ro-vibrational Hamiltonian operators via a gateway Hamiltonian operator

    SciTech Connect

    Szalay, Viktor

    2015-05-07

    A new ro-vibrational Hamiltonian operator, named gateway Hamiltonian operator, with exact kinetic energy term, T-hat, is presented. It is in the Eckart frame and it is of the same form as Watson’s normal coordinate Hamiltonian. However, the vibrational coordinates employed are not normal coordinates. The new Hamiltonian is shown to provide easy access to Eckart frame ro-vibrational Hamiltonians with exact T-hat given in terms of any desired set of vibrational coordinates. A general expression of the Eckart frame ro-vibrational Hamiltonian operator is given and some of its properties are discussed.

  10. BEER analysis of Kepler and CoRoT light curves. III. Spectroscopic confirmation of seventy new beaming binaries discovered in CoRoT light curves

    NASA Astrophysics Data System (ADS)

    Tal-Or, L.; Faigler, S.; Mazeh, T.

    2015-08-01

    Context. The BEER algorithm searches stellar light curves for the BEaming, Ellipsoidal, and Reflection photometric modulations that are caused by a short-period companion. These three effects are typically of very low amplitude and can mainly be detected in light curves from space-based photometers. Unlike eclipsing binaries, these effects are not limited to edge-on inclinations. Aims: Applying the algorithm to wide-field photometric surveys such as CoRoT and Kepler offers an opportunity to better understand the statistical properties of short-period binaries. It also widens the window for detecting intrinsically rare systems, such as short-period brown-dwarf and massive-planetary companions to main-sequence stars. Methods: Applying the search to the first five long-run center CoRoT fields, we identified 481 non-eclipsing candidates with periodic flux amplitudes of 0.5-87 mmag. Optimizing the Anglo-Australian-Telescope pointing coordinates and the AAOmega fiber-allocations with dedicated softwares, we acquired six spectra for 231 candidates and seven spectra for another 50 candidates in a seven-night campaign. Analysis of the red-arm AAOmega spectra, which covered the range of 8342-8842 Å, yielded a radial-velocity precision of ~1 km s-1. Spectra containing lines of more than one star were analyzed with the two-dimensional correlation algorithm TODCOR. Results: The measured radial velocities confirmed the binarity of seventy of the BEER candidates - 45 single-line binaries, 18 double-line binaries, and 7 diluted binaries. We show that red giants introduce a major source of false candidates and demonstrate a way to improve BEER's performance in extracting higher fidelity samples from future searches of CoRoT light curves. The periods of the confirmed binaries span a range of 0.3-10 days and show a rise in the number of binaries per ΔlogP toward longer periods. The estimated mass ratios of the double-line binaries and the mass ratios assigned to the single

  11. Arrachements des épines iliaques antéro-supérieures et antéro-inférieures chez l'adolescent sportifs: à propos de deux cas

    PubMed Central

    Louaste, Jamal; Cherrad, Taoufik; Rachid, Khalid

    2015-01-01

    Les arrachements des épines iliaques antéro-supérieures et antéro-inférieures sont des entités rares qui touchent surtout l'enfant et l'adolescent. Elles se voient généralement lors d'une activité sportive. Le tableau clinique est dominé par une douleur brutale et importante de la hanche de type mécanique. Alors que le diagnostic est confirmé par les examens radiologiques. Nous rapportons deux cas de fractures arrachement des épines iliaques l'une antéro-supérieure et l'autre antéro-inférieure. PMID:26985274

  12. Side band suppression for wide band optical RoF systems

    NASA Astrophysics Data System (ADS)

    Abir, Hraghi; Ben Abid, Samir; Menif, Mourad

    2015-05-01

    In this paper, we propose a flexible monocycle generator that is based on multi-tonal excitation of a dual-arm MZM. The proposed generator permits the generation of different waveforms, such as Gaussian, first order Gaussian derivative, sinusoidal, cosine and sinc pulses. We exploit the proposed generator in order to generate the International Telecommunication Union-Radiocommunication( ITU-R) recommended channelization which contains four carrier frequencies, spaced by 2.16 GHz (58.32 GHz, 60.48 GHz, 62.64 GHz and 64.80 GHz). This millimeter waves (mmwaves) have attracted a great deal of attention in the Radio over Fiber (RoF) systems. The main challenge of the RoF system is to provide higher bands and increase significantly data rate with using millimeter-wave (mm-wave) band.

  13. Magnetic order on a frustrated lattice due to orbital degrees of freedom in RO2 hyperoxides

    NASA Astrophysics Data System (ADS)

    Oleś, Andrzej M.; Wohlfeld, Krzysztof; Daghofer, Maria

    2012-02-01

    The alkali RO2 hyperoxides (R=Rb,Cs,K) crystallize in a frustrated bct lattice. Nevertheless, all of the members of the family of alkali RO2 hyperoxides have long range layered C-type antiferromagnetic (C-AF) order at low temperature. We show that including the almost degenerate p-orbital degrees of freedom in a realistic spin-orbital model can resolve this contradiction [1]. Although a priori the orbital degrees of freedom do not remove frustration in spin system, we show that the anomalously large interorbital hopping together with the orbital order induced by the lattice stabilize the C-AF order in this class of compounds, in agreement with generalized Goodenough-Kanamori rules formulated here. [4pt] [1] K. Wohlfeld, M. Daghofer, and A.M. Ole's, EPL 96, 27001 (2011).

  14. Aspects of the Eckart frame ro-vibrational kinetic energy operator

    NASA Astrophysics Data System (ADS)

    Szalay, Viktor

    2015-08-01

    A most decisive part of developing the Eckart frame ro-vibrational kinetic energy operator (KEO) in terms of curvilinear internal coordinates is the introduction of vibrational displacements obeying the Eckart conditions. It is examined here, how such displacements may be constructed by orthogonal and nonorthogonal transformations, and how they can be employed in developing the KEO. In particular, it is shown analytically, by term by term comparison, that the Eckart KEOs obtained by employing Pickett's method and the gateway Hamiltonian method are equivalent. That is, although it may appear in the form of very different expressions, the general, exact ro-vibrational Eckart frame KEO is unique. As side result, it has been shown that the simple formula of the pseudo-potential derived by Watson for the exact KEO given in normal coordinates applies to any Eckart frame KEO, irrespective of the choice of the vibrational coordinates.

  15. Simple and reconfigured single-sideband OFDM RoF system.

    PubMed

    Xu, Yuming; Li, Xinying; Yu, Jianjun; Chang, Gee-Kung

    2016-10-03

    We propose a simple and reconfigured dispersion-tolerant single sideband (SSB) orthogonal frequency division multiplexing (OFDM) radio over fiber (RoF) system enabled by digital signal processing (DSP), one in-phase/quadrature (I/Q) modulator and direct-detection. The generated radio frequency (RF) is based on DSP and the frequency can be flexibly adjusted, which can be employed in the future software-defined radio access network (RAN). Based on our proposed system, we have experimentally demonstrated 16-ary quadrature amplitude modulation (16QAM) 21.87-Gb/s 21-GHz and 38-GHz SSB-OFDM RoF signal generation and transmission over 80-km single-mode fiber (SMF), respectively.

  16. Stellar parameters for stars of the CoRoT exoplanet field

    NASA Astrophysics Data System (ADS)

    Cortés, C.; Maciel, S. C.; Vieira, S.; Ferreira Lopes, C. E.; Leão, I. C.; de Oliveira, G. P.; Correia, C.; Canto Martins, B. L.; Catelan, M.; De Medeiros, J. R.

    2015-09-01

    Context. Spectroscopic observations represent a fundamental step in the physical characterization of stars and, in particular, in the precise location of stars in the HR diagram. Rotation is also a key parameter, impacting stellar properties and evolution, which modulates the interior and manifests itself on the surface of stars. To date, the lack of analysis based on large samples has prevented our understanding of the real impact of stellar parameters and rotation on the stellar evolution as well as on the behavior of surface abundances. The space missions, CoRoT and Kepler, are providing us with rotation periods for thousands of stars, thus enabling a robust assessment of the behavior of rotation for different populations and evolutionary stages. For these reasons, the follow-up programs are fundamental to increasing the returns of these space missions. An analysis that combines spectroscopic data and rotation/modulation periods obtained from these space missions provides the basis for establishing the evolutionary behavior of the angular momentum of solar-like stars at different evolutionary stages, and the relation of rotation with other relevant physical and chemical parameters. Aims: To support the computation and evolutionary interpretation of periods associated with the rotational modulation, oscillations, and variability of stars located in the CoRoT fields, we are conducting a spectroscopic survey for stars located in the fields already observed by the satellite. These observations allow us to compute physical and chemical parameters for our stellar sample. Methods: Using spectroscopic observations obtained with UVES/VLT and Hydra/Blanco, and based on standard analysis techniques, we computed physical and chemical parameters (Teff, log (g), [Fe/H], vmic, vrad, vsin (i), and A(Li)) for a large sample of CoRoT targets. Results: We provide physical and chemical parameters for a sample comprised of 138 CoRoT targets. Our analysis shows the stars in our

  17. Membrane autopsy based bio-fouling investigation of distillery spent wash RO treatment plant.

    PubMed

    Sharma, Pinki; Joshi, Himanshu

    2014-01-01

    In this paper, a thorough investigation has been done to evaluate the effects of different pollutants on membrane performance by autopsy. Autopsy was performed on fresh and fouled reverse osmosis (RO) membrane elements from a distillery spent wash treatment plant by different analyses, such as field emission scanning electron microscopy, atomic force microscopy, Fourier transform infrared spectroscopy and X-ray diffraction, to identify the cause of poor performance of an RO plant. Results obtained from the analysis of membranes indicate that a mixture of colloids and organic matters (polysaccharides and amines) along with the presence of multivalent ions (Ca, Mg, Fe and SO4) causes membrane fouling, which in turn affects membrane performance. Possible measures to improve treated effluent quality and mitigate fouling have been suggested for this particular case study.

  18. Thematic trip: "Save Roşia MontanÄă"

    NASA Astrophysics Data System (ADS)

    Eugenia, Marcu

    2015-04-01

    The name Roşia Montană, situated in Transylvania, became well known after a Romanian-Canadian company, Roşia Montană Gold Company (RMGC), obtained the concession license on exploitation for gold and silver minerals in the Roşia Montană area. The project consists of opening the largest surface gold mines in Europe using cyanide, which will include four open pits and a processing plant for gold and silver in The Roşia Valley and a tailings facility with an area of 367 hectares in the Corna Valley. One of the main fears is related to a possible ecological accident like the one in Baia Mare in 2000, when a tailing facility dam break led to cyanide pollution of Tisa and Danube rivers that resulted in the death of 1,200 tons of fish and contamination of water resources for 2 million people. This thematic trip is important for the scientific preparation of students and an opportunity to educate them in the spirit of environmental protection. The training and education of students will require assimilation and understanding, actively and consciously, using the knowledge acquired during the compulsory curriculum and training skills. REASON: The continuous degradation of the environment is a major crisis due to human intervention in nature, and the proposed Roşia Montană mining project will continue this trend. The company proposes to extract gold from mines by using the gold separation technique using cyanide, a process that involves destroying a total area of 16 km² which includes 5 mountains, 7 churches, 11 cemeteries and the ruins of Alburnus Maior Citadel, as well as creating pollution that would last for hundreds of years. The extraction of gold from low-grade ores using cyanide processes was estimated to result in a worldwide emission of 45,300 tons of hydrogen cyanide. Environmental education for a healthy life has children as target group, because they are the trustees and beneficiaries of tomorrow's natural resources and can influence the attitudes of

  19. Detection of new pulsations in the roAp star HD 177765

    NASA Astrophysics Data System (ADS)

    Holdsworth, Daniel L.

    2016-10-01

    We report the discovery of 2 previously undetected pulsation frequencies in the known roAp star HD 177765. Photometric observations by the Kepler space telescope during K2 Campaign 7 show low-amplitude pulsations (4-11 micro mag) previously unseen in photometry. We show the pulsations to be stable over the observation period, and demonstrate that the separation of the frequencies is not representative of the large frequency separation quantity needed to perform asteroseismic analysis.

  20. Multiple dose study of the combined radiosensitizers Ro 03-8799 (pimonidazole) and SR 2508 (etanidazole)

    SciTech Connect

    Bleehen, N.M.; Newman, H.F.; Maughan, T.S.; Workman, P.

    1989-04-01

    The hypoxic cell radiosensitizers Ro 03-8799 and SR 2508 have different clinical toxicities. The former produces an acute but transient central nervous system syndrome, whereas the latter produces cumulative peripheral neuropathy. Following single dose studies, an escalating multiple dose schedule using both drugs in combination showed no unexpected adverse reactions at lower doses. This study identifies the clinical tolerance and pharmacokinetics when doses in the region of the maximal tolerated dose are given to 26 patients receiving infusions of 0.75 g/m2 Ro 03-8799 and 2 g/m2 SR 2508 three times per week. At 15 doses, 3/4 patients experienced WHO grade 2 peripheral neuropathy, whereas at 12 doses 1/9 developed grade 2 and 6/9 developed grade 1 neuropathies. This represents a lower dose of SR 2508 than can be given alone suggesting that some interaction between the two drugs does exist in terms of chronic peripheral neurotoxicity. Pharmacokinetic studies show no adverse interactions between the two drugs and minimal inter-patient variation. From bivariate analysis, cumulative AUC for Ro 03-8799 has the most significant correlation with the development of peripheral neuropathy. Tumor drug concentrations normalized to the administered dose show mean values of 34 micrograms/g Ro 03-8799 and 76 micrograms/g SR 2508 30 minutes after infusion. These could be expected to produce a single dose sensitizer enhancement ratio of 1.5. The combination of the two sensitizers at the maximum tolerable dose may be expected to give an increased therapeutic efficacy over either drug alone.

  1. VizieR Online Data Catalog: CoRoT 105906206 frequencies analysis (da Silva+, 2014)

    NASA Astrophysics Data System (ADS)

    da Silva, R.; Maceroni, C.; Gandolfi, D.; Lehmann, H.; Hatzes, A. P.

    2014-03-01

    The file frequenc.dat contains the table with 220 frequencies, amplitudes, and phases, together with their uncertainties, derived for the light curve of CoRoT 105906206 with pulsations only (after subtracting the best binary model). The uncertainties are the formal values computed using equations (4), (10), and (11) of Montgomery & O'Donoghue (1999DSSN...13...28M). (1 data file).

  2. Exploring the Helium Core of the δ Scuti Star CoRoT 102749568 with Asteroseismology

    NASA Astrophysics Data System (ADS)

    Chen, Xinghao; Li, Yan; Lin, Guifang; Chen, Yanhui; Guo, Junjun

    2017-01-01

    Based on regularities in rotational splitting, we seek possible multiplets for the observed frequencies of CoRoT 102749568. There are 21 sets of multiplets identified, including four sets of multiplets with l = 1, nine sets of multiplets with l = 2, and eight sets of multiplets with l = 3. In particular, there are three complete triplets (f10, f12, f14), (f31, f34, f35), and (f41, f43, f44). The rotational period of CoRoT 102749568 is estimated to be {1.34}-0.05+0.04 days. When doing model fittings, three l = 1 modes (f12, f34, and f43) and the radial first overtone f13 are used. Our results shows that the three nonradial modes (f12, f34, and f43) are mixed modes, which mainly provide constraints on the helium core. The radial first overtone f13 mainly provides constraint on the stellar envelope. Hence the size of the helium core of CoRoT 102749568 is determined to be {M}{He} = 0.148 ± 0.003 M⊙ and {R}{He} = 0.0581 ± 0.0007 R⊙. The fundamental parameters of CoRoT 102749568 are determined to be M = 1.54 ± 0.03 M⊙, Z=0.006, {f}{ov}=0.004+/- 0.002, {log} g=3.696+/- 0.003, {T}{eff}=6886+/- 70 K, R = 2.916 ± 0.039 R⊙, and L = 17.12 ± 1.13 L⊙.

  3. Raman investigation of ro-vibrational modes of interstitial H2 in Si

    NASA Astrophysics Data System (ADS)

    Koch, S. G.; Lavrov, E. V.; Weber, J.

    2012-08-01

    A Raman scattering study of ro-vibrational transitions Q(J) of the interstitial H2 in Si is presented. It is shown that the Q(2) mode of para hydrogen is coupled to the TAX phonon of Si. The mode appears in the spectra at temperatures above 200 K. The results presented also suggest that the Q(3) transition of ortho hydrogen is resonantly coupled to the OΓ phonon.

  4. Benzodiazepine receptor binding in vivo with (/sup 3/)-Ro 15-1788

    SciTech Connect

    Goeders, N.E.; Kuhar, M.J.

    1985-07-29

    In vivo benzodiazepine receptor binding has generally been studied by ex vivo techniques. In this investigation, the authors identify the conditions where (/sup 3/H)-Ro 15-1788 labels benzodiazepine receptors by true in vivo binding, i.e. where workable specific to nonspecific ratios are obtained in intact tissues without homogenization or washing. (/sup 3/H)-Flunitrazepam and (/sup 3/H)-clonazepam did not exhibit useful in vivo receptor binding. 39 references, 5 figures, 1 table.

  5. CoRoT observations of the young open cluster Dolidze 25

    NASA Astrophysics Data System (ADS)

    Ripepi, V.; Leccia, S.; Baglin, A.; Ruoppo, A.; Bernabei, S.; Zwintz, K.; Cusano, F.; Gandolfi, D.; Guenter, E. W.; Alencar, S.; Marconi, M.; Monteiro, M. J. P. F. G.; Palla, F.; Alcalá, J. M.; Boehm, T.; Catala, C.; Chavero, C.; Corradi, W. S.; Degl'Innocenti, S.; de La Reza, R.; Deluil, M.; Favata, F.; Fernandez, M.; Gregorio-Hetem, J.; Lepine, J. D. R.; Pinheiro, F. J. G.; Prada Moroni, P. G.; Quast, G.; Torres, C. A. O.; Weiss, W.

    2010-07-01

    We present some preliminary results based on the CoRoT observations of the young distant cluster Dolidze 25. The light curve for the 28 stars observed by the satellite have been analyzed and the relevant periodogram presented. As a result we have found two binary, three Pulsating Be, three SPB, two Spotted and one ellipsoidal variables. Noteworthy, we have also identified one PMS δ Scuti candidate.

  6. Antiscalant removal in accelerated desupersaturation of RO concentrate via chemically-enhanced seeded precipitation (CESP).

    PubMed

    McCool, Brian C; Rahardianto, Anditya; Cohen, Yoram

    2012-09-01

    An experimental study was carried out to demonstrate and quantify the feasibility of antiscalant (AS) removal from brackish water RO concentrate of high gypsum scaling propensity via lime treatment prior to seeded gypsum precipitation. Based on studies with model solutions, it was shown that sufficient AS removal (up to ∼90%) from RO concentrate is feasible via a lime treatment step (at a dose significantly lower than that required for conventional lime softening) to enable effective subsequent seeded gypsum precipitation. This two-step chemically-enhanced seeded precipitation (CESP) treatment of primary RO concentrate is suitable as an intermediate concentrate demineralization (ICD) stage for high recovery desalting employing secondary RO desalination. Analysis of gypsum precipitation and lime treatment kinetic data suggests that, after adequate CaCO(3) precipitation has been induced for effective AS scavenging, CaSO(4) desupersaturation can be achieved via seeded gypsum precipitation without retardation due to seed poisoning by AS. Also, the lime dose required to prevent seed poisoning during subsequent gypsum desupersaturation via seeded gypsum precipitation can be adequately assessed with a precipitation kinetics model that considers AS seed poisoning based on a Langmuir adsorption isotherm. The degree of AS removal after lime treatment increased linearly with the logarithm of the single lime dose additions. Staged lime dosing (i.e., multiple lime additions), however, removed a higher degree of AS relative to an equivalent single lime dose addition since a higher driving force for CaCO(3) precipitation could be maintained over the course of the lime treatment period.

  7. Growth conditions, compact perturbations and operator subdecomposability, with applications to generalized Cesàro operators

    NASA Astrophysics Data System (ADS)

    Miller, T. L.; Miller, V. G.; Neumann, M. M.

    2005-01-01

    We adapt recent results of Albrecht and Ricker to obtain conditions under which growth constraints on the left resolvent of a Banach space operator are preserved under suitable perturbations. As an application, we establish Bishop's property ([beta]) for certain generalized Cesàro operators on the classical Hardy spaces Hp, 1

  8. Learning to Improve E-mail Classification with numéro interactive

    NASA Astrophysics Data System (ADS)

    Jones, Dean M.

    This paper describes some of the ways in which we use artificial intelligence technologies in numéro interactive, a Customer Interaction Management system. In particular, we focus on the classification of e-mail messages into one of multiple business categories. We describe different features that are extracted from e-mail messages to help in this classification, and the improvement in the overall classification accuracy that results from the use of each kind of feature.

  9. Removal of emerging contaminants from municipal wastewater with an integrated membrane system, MBR-RO.

    PubMed

    Dolar, Davor; Gros, Meritxell; Rodriguez-Mozaz, Sara; Moreno, Jordi; Comas, Joaquim; Rodriguez-Roda, Ignasi; Barceló, Damià

    2012-11-15

    The presence of emerging contaminants in the aquatic environment and their potential effects on living organisms has become an issue of growing concern. Among emerging contaminants, pharmaceuticals may enter the aquatic environment due to their high consumption and their incomplete removal in conventional municipal wastewater treatment plants (WWTPs). The main goal of this study was the assessment of the removal efficiency of pharmaceuticals found in municipal wastewater of a coastal WWTP (Castell-Platja d'Aro, Spain) using an integrated pilot scale membrane system (MBR-RO). Twenty multiple-class pharmaceuticals (including psychiatric drugs, macrolide antibiotics, β-blockers, sulfonamide and fluoroquinolone antibiotics, histamine H2 receptor antagonists, anti-inflammatories, nitroimidazole, β-agonist and antiplatelet agent) were measured in real influent with the lowest average concentration for psychiatric drugs (0.017 μg L(-1)) to the highest for macrolide antibiotics (2.02 μg L(-1)). Although some contaminants were in relatively high concentrations (even up to 2.90 μg L(-1) in the case of ofloxacin). The combination of MBR and RO treatment showed excellent overall removal of target emerging contaminants with removal rates above 99% for all of them. For some compounds (metronidazole, hydrocodone, codein, ranitidine) MBR provided high removal efficiency (up to 95%). Additionally RO membrane showed removal rates always higher than 99%.

  10. THE CoRoT DISCOVERY OF A UNIQUE TRIPLE-MODE CEPHEID IN THE GALAXY

    SciTech Connect

    Poretti, E.; Baglin, A.; Weiss, W. W.

    2014-11-10

    The exploitation of the CoRoT treasure of stars observed in the exoplanetary field allowed the detection of a unusual triple-mode Cepheid in the Milky Way, CoRoT 0223989566. The two modes with the largest amplitudes and a period ratio of 0.80 are identified with the first (P {sub 1} = 1.29 days) and second (P {sub 2} = 1.03 days) radial overtones. The third period, which has the smallest amplitude but is able to produce combination terms with the other two, is the longest one (P {sub 3} = 1.89 days). The ratio of 0.68 between the first-overtone period and the third period is the unusual feature. Its identification with the fundamental radial or a nonradial mode is discussed with respect to similar cases in the Magellanic Clouds. In both cases, the period triplet and the respective ratios make the star unique in our Galaxy. The distance derived from the period-luminosity relation and the galactic coordinates put CoRoT 0223989566 in the metal-rich environment of the ''outer arm'' of the Milky Way.

  11. Ro-vibrational excitation, alignment and orientation distributions of fast non-dissociatively scattered molecules

    NASA Astrophysics Data System (ADS)

    Harder, R.; Snowdon, K. J.

    1997-12-01

    The ro-vibrational distribution of fast diatomic molecules scattered from an uncorrugated surface under strongly dissipative glancing incidence conditions is calculated. The classical trajectory simulation includes potential surface switching associated with hot-electron scattering processes. Both ro-vibrational excitation and strong alignment of the classical angular momentum vector in the surface plane ("cartwheel motion") are observed, independent of the occurrence of potential surface switching. Ro-vibrational excitation is enhanced strongly by transitions between potential surfaces. The resultant larger proportion of molecules in highly rotationally excited states leads to a higher fraction of cartwheel-aligned molecules in the scattered molecule ensemble. The molecules which dissociate in the simulation are characterised by surface normal peaked internuclear axis orientation distributions. This is in agreement with the results of recent experiments [A. Nesbitt et al., Surf. Sci. 331-333 (1995) 321]. We observe, in addition, an enhanced rotational population of "topspin" oriented molecules, which arises from differences in the surface parallel oriented friction forces acting on each atom of the molecule. Glancing incidence scattering from well-prepared close-packed metal surfaces would appear to provide an efficient, general method to obtain a beam of preferentially aligned fast neutral diatomic molecules.

  12. Water Quality of Hills Water, Supply Water and RO Water Machine at Ulu Yam Selangor

    NASA Astrophysics Data System (ADS)

    Ngadiman, N.; ‘I Bahari, N.; Kaamin, M.; Hamid, N. B.; Mokhtar, M.; Sahat, S.

    2016-07-01

    The rapid development resulted in the deterioration of the quality of drinking water in Malaysia. Recognizing the importance of water quality, new alternatives for drinking water such as mineral water processing from reverse osmosis (RO) machine become more popular. Hence, the demand for mineral water, natural spring water or water from the hills or mountains rose lately. More consumers believed the quality of these spring water better than other source of drinking water. However, the quality of all the drinking water sources is to meet the required quality standard. Therefore, this paper aims to measure the quality of the waters from hills, from RO machine and the water supply in Ulu Yam, Selangor Batang Kali, Malaysia. The water quality was determined based on following parameters: ammoniacal nitrogen (NH3), iron (Fe), turbidity (NTU) and pH. The results show that the water from hills has better quality compared to water supply and water from RO machine. The value of NH3 ranged from 0.03 mg/L- 0.67 mg/L; Fe was from 0.03mg/L - 0.12 mg/L, turbidity at 0.42 NTU - 0.88 NTU and pH is at 6.60 - 0.71. Based on the studied parameters, all three types of water are fit for drinking and have met the required national drinking water quality standard.

  13. Threshold scaling limits of RO concentrates flowing in a long waste disposal pipeline.

    PubMed

    Semiat, R; Hasson, D; Zelmanov, G; Hemo, I

    2004-01-01

    Disposal of RO concentrates emanating from inland brackish water desalination plants presents a difficult environmental problem. The solution adopted by Mekorot--the National Water Company of Israel--is to construct a 30 km waste disposal pipeline for collecting concentrates emanating from several RO desalination plants and discharging them into the sea. The discharged concentrates are highly supersaturated with respect to CaCO3. Scale precipitation during concentrate flow through the RO module is inhibited by the presence of anti-scalants. The retention time of the concentrate solution in the discharge pipe will exceed 100 hours. This raises the issue of the risk of scale precipitation in the discharge pipe that could impair its proper functioning. The aim of the present study was to provide data for guiding the design and operation of the disposal pipeline. The extent of the induction period prior to the onset of precipitation was measured in a pilot plant simulating flow of concentrate solutions dosed with anti-scalants. The parameters investigated were the scaling potential, the anti-scalant concentration and the presence of a mixture of several anti-scalants. The results of this study provide threshold scaling limits under various conditions.

  14. [Demographic profile of Boróro Indians from Mato Grosso State, Brazil, 1993-1996].

    PubMed

    Souza, Luciene Guimarães de; Pagliaro, Heloisa; Santos, Ricardo Ventura

    2009-02-01

    This paper analyzes the demographic profile of the Boróro Indians from Mato Grosso State, Brazil, from 1993 to 1996. Data came from annual collection and registration of vital statistics conducted by the health service in three villages (Garças, Meruri, and Morada dos Boróro). The average annual population growth rate was 2.4%. Nearly half (44%) of the population was younger than 15 years (median 16 years). The crude birth rate was 30.9 per 1,000 and the crude death rate 7.3 per 1,000 inhabitants. The infant mortality rate was high (58.8 per thousand live births), probably resulting from precarious health conditions in the villages. The results showed that women married younger than men and that there were numerous unmarried adult men (26.7%) and women (13.3%), as compared to data from other indigenous groups. The total fertility rate of Boróro women was 4.3, quite low compared to other indigenous communities in Brazil. The study emphasizes the importance of systematically collecting and analyzing demographic data on indigenous populations.

  15. On Cesàro Limit Distribution of a Class of Permutative Cellular Automata

    NASA Astrophysics Data System (ADS)

    Maass, Alejandro; Martinez, Servet

    1998-01-01

    We study Cesàro means (time averages) of the evolution measures of the class of permutative cellular automata over {0, 1}ℕ defined by (\\varphi _B x)_n = x_{n{kern 1pt} {kern 1pt} + {kern 1pt} {kern 1pt} R} + Pi _{j{kern 1pt} {kern 1pt} = {kern 1pt} {kern 1pt} 0}^{R{kern 1pt} {kern 1pt} - {kern 1pt} {kern 1pt} 1} {kern 1pt} {kern 1pt} {kern 1pt} {kern 1pt} {kern 1pt} {kern 1pt} (1 + b_j + x_{n{kern 1pt} {kern 1pt} + {kern 1pt} {kern 1pt} j} ) where B= b 0 ⋯ b R-1is an aperiodic block in {0, 1} R and operations are taken mod 2. If the initial measure is Bernoulli, we prove that the limit of the Cesàro mean of the first column distribution exists. When R = 1 and B = 1, φ B is the mod 2 sum automaton. For this automaton we show that the limit is the (1/2, 1/2(-Bernoulli measure, and if the initial measure is Markov, we show that the limit of Cesàro mean of the one-site distribution is equidistributed.

  16. Tropical temperature variability and Kelvin-wave activity in the UTLS from GPS RO measurements

    NASA Astrophysics Data System (ADS)

    Scherllin-Pirscher, Barbara; Randel, William J.; Kim, Joowan

    2017-01-01

    Tropical temperature variability over 10-30 km and associated Kelvin-wave activity are investigated using GPS radio occultation (RO) data from January 2002 to December 2014. RO data are a powerful tool for quantifying tropical temperature oscillations with short vertical wavelengths due to their high vertical resolution and high accuracy and precision. Gridded temperatures from GPS RO show the strongest variability in the tropical tropopause region (on average 3 K2). Large-scale zonal variability is dominated by transient sub-seasonal waves (2 K2), and about half of sub-seasonal variance is explained by eastward-traveling Kelvin waves with periods of 4 to 30 days (1 K2). Quasi-stationary waves associated with the annual cycle and interannual variability contribute about a third (1 K2) to total resolved zonal variance. Sub-seasonal waves, including Kelvin waves, are highly transient in time. Above 20 km, Kelvin waves are strongly modulated by the quasi-biennial oscillation (QBO) in stratospheric zonal winds, with enhanced wave activity during the westerly shear phase of the QBO. In the tropical tropopause region, however, peaks of Kelvin-wave activity are irregularly distributed in time. Several peaks coincide with maxima of zonal variance in tropospheric deep convection, but other episodes are not evidently related. Further investigations of convective forcing and atmospheric background conditions are needed to better understand variability near the tropopause.

  17. RoCoMAR: robots' controllable mobility aided routing and relay architecture for mobile sensor networks.

    PubMed

    Le, Duc Van; Oh, Hoon; Yoon, Seokhoon

    2013-07-05

    In a practical deployment, mobile sensor network (MSN) suffers from a low performance due to high node mobility, time-varying wireless channel properties, and obstacles between communicating nodes. In order to tackle the problem of low network performance and provide a desired end-to-end data transfer quality, in this paper we propose a novel ad hoc routing and relaying architecture, namely RoCoMAR (Robots' Controllable Mobility Aided Routing) that uses robotic nodes' controllable mobility. RoCoMAR repeatedly performs link reinforcement process with the objective of maximizing the network throughput, in which the link with the lowest quality on the path is identified and replaced with high quality links by placing a robotic node as a relay at an optimal position. The robotic node resigns as a relay if the objective is achieved or no more gain can be obtained with a new relay. Once placed as a relay, the robotic node performs adaptive link maintenance by adjusting its position according to the movements of regular nodes. The simulation results show that RoCoMAR outperforms existing ad hoc routing protocols for MSN in terms of network throughput and end-to-end delay.

  18. Galactic archaeology with asteroseismology and spectroscopy: Red giants observed by CoRoT and APOGEE

    NASA Astrophysics Data System (ADS)

    Anders, F.; Chiappini, C.; Rodrigues, T. S.; Miglio, A.; Montalbán, J.; Mosser, B.; Girardi, L.; Valentini, M.; Noels, A.; Morel, T.; Johnson, J. A.; Schultheis, M.; Baudin, F.; de Assis Peralta, R.; Hekker, S.; Themeßl, N.; Kallinger, T.; García, R. A.; Mathur, S.; Baglin, A.; Santiago, B. X.; Martig, M.; Minchev, I.; Steinmetz, M.; da Costa, L. N.; Maia, M. A. G.; Allende Prieto, C.; Cunha, K.; Beers, T. C.; Epstein, C.; García Pérez, A. E.; García-Hernández, D. A.; Harding, P.; Holtzman, J.; Majewski, S. R.; Mészáros, Sz.; Nidever, D.; Pan, K.; Pinsonneault, M.; Schiavon, R. P.; Schneider, D. P.; Shetrone, M. D.; Stassun, K.; Zamora, O.; Zasowski, G.

    2017-01-01

    With the advent of the space missions CoRoT and Kepler, it has recently become feasible to determine precise asteroseismic masses and relative ages for large samples of red giant stars. We present the CoRoGEE dataset, obtained from CoRoT light curves for 606 red giants in two fields of the Galactic disc that have been co-observed by the Apache Point Observatory Galactic Evolution Experiment (APOGEE). We used the Bayesian parameter estimation code PARAM to calculate distances, extinctions, masses, and ages for these stars in a homogeneous analysis, resulting in relative statistical uncertainties of ≲2% in distance, 4% in radius, 9% in mass and 25% in age. We also assessed systematic age uncertainties stemming from different input physics and mass loss. We discuss the correlation between ages and chemical abundance patterns of field stars over a broad radial range of the Milky Way disc (5 kpc RoGEE observations of a chemodynamical Milky Way disc model indicate that the number of high-metallicity stars in the outer disc is too high to be accounted for even by the strong radial mixing present in the model. The mock observations also show that the age distribution of the [α/Fe]-enhanced sequence in the CoRoGEE inner-disc field is much broader than expected from a combination of radial mixing and observational errors. We suggest that a thick-disc/bulge component that formed stars for more than 3 Gyr may account for these discrepancies. Our results are subject to future improvements due to (a) the still low statistics, because our sample had to be

  19. Evaluation of the ethanol antagonist' Ro15-4513 on cardiovascular and metabolic responses induced by ethanol

    SciTech Connect

    Lerner, M.R.; Gauvin, D.V.; Holloway, F.A.; Wilson, M.F.; Brackett, D.J. Veterans Affairs Medical Center, Oklahoma City, OK )

    1992-02-26

    The putative ethanol antagonist Ro15-4513 has been reported to attenuate many behavioral responses induced by ethanol, including motor coordination, narcosis, ethanol self administration and intake, and anticonvulsant actions. This study was designed to study the effect of Ro15-4513 on cardiovascular and metabolic responses elicited by intragastric ethanol in conscious rats. Four groups of rats were catheterized under enflurane anesthesia and allowed to regain consciousness. Each group was given either 3.2, 10.0, or 32.0 mg/kg Ro15-4513 or equivalent Tween (i.p.) following ethanol. Ro15-4513 had no effect at any concentration on the decreases in mean arterial pressure, cardiac output, central venous pressure, respiration rate, and cardiac stroke volume and the increases in systemic vascular resistance, heart rate, and glucose evoked by the ethanol challenge. Blood alcohol concentrations measured throughout the study were not affected by any concentration of Ro15-4513. These data suggest that even though Ro15-4513 has significant effects on behavioral responses induced by ethanol it has no effect on the cardiovascular and metabolic responses elicited during ethanol intoxication.

  20. Standard and Short RoM Isokinetic Testing: Comparative Analysis in Identifying Submaximal Shoulder External Rotator Effort.

    PubMed

    Pujol, Eduard; Chaler, Joaquim; Sucarrats, Laura; López, Inés; Zeballos, Blanca; Garreta, Roser; Dvir, Zeevi

    2017-01-31

    An isokinetic-related parameter termed the difference between eccentric-concentric strength ratios at two distinct test velocities (DEC) based on 60° (standard) range of motion (RoM) has been proven to be highly efficient detecting feigned muscular efforts. This study aimed to verify whether a DEC derived from a much shorter test RoM (20°) was equally useful than a long RoM-derived one. Eighteen healthy men (32.4 ± 6.4 years old) took part in a study focusing on shoulder external rotation isokinetic strength. Participants performed a genuine shoulder external rotator maximal effort (eight pairs of concentric and eccentric contractions at high and low velocities at short and long RoM) and then instructed to feign maximal effort. Contraction velocities were adjusted accordingly by applying a 1:4 gradient and peak moments registered. Both condition DEC was then calculated by subtracting the eccentric and concentric strength ratios at low velocities from those at high velocities. DEC scores in the feigned effort were significantly higher than maximal effort ones in both conditions in men. It enabled the setting of specific cutoff levels for separating the efforts. Both approaches revealed a coincident sensitivity (78%) whereas short RoM showed an even higher specificity: 88% versus 78%. Thus, the short RoM protocol provides clinically acceptable detection power.

  1. The interactions with Ro60 and La differentially affect nuclear export of hY1 RNA.

    PubMed Central

    Simons, F H; Rutjes, S A; van Venrooij, W J; Pruijn, G J

    1996-01-01

    Ro RNPs are evolutionarily conserved ribonucleoprotein particles that consist of a small RNA, known as Y RNA, associated with several proteins, such as La, Ro60, and Ro52. The Y RNAs (Y1-Y5), which are transcribed by RNA polymerase III, have been shown to reside almost exclusively in the cytoplasm as Ro RNPs. To obtain more insight into the nuclear export pathway of Y RNAs, hY1 RNA export was studied in Xenopus laevis oocytes. Injection of various hY1 RNA mutants showed that an intact Ro60 binding site is a prerequisite for nuclear export, whereas the presence of an intact La binding site resulted in strong nuclear retention of hY1 RNA. Competition studies with various classes of RNAs indicated that, in addition to Ro60, another titratable factor was necessary for nuclear export of hY1 RNA. This factor appears also to be involved in nuclear export of tRNA. Because export of hY1 RNA could not be blocked by a synthetic peptide containing the recently identified nuclear export signal of the HIV-1 Rev protein, nuclear export of hY1 RNA does not seem to be dependent on a Rev-like nuclear export signal. PMID:8608450

  2. Determination of the in vivo redox potential using roGFP and fluorescence spectra obtained from one-wavelength excitation

    NASA Astrophysics Data System (ADS)

    Wierer, S.; Elgass, K.; Bieker, S.; Zentgraf, U.; Meixner, A. J.; Schleifenbaum, F.

    2011-02-01

    The analysis of molecular processes in living (plant) cells such as signal transduction, DNA replication, carbon metabolism and senescence has been revolutionized by the use of green fluorescent protein (GFP) and its variants as specific cellular markers. Many cell biological processes are accompanied by changes in the intracellular redox potential. To monitor the redox potential, a redox-sensitive mutant of GFP (roGFP) was created, which shows changes in its optical properties in response to changes in the redox state of its surrounding medium. For a quantitative analysis in living systems, it is essential to know the optical properties of roGFP in vitro. Therefore, we applied spectrally resolved fluorescence spectroscopy on purified roGFP exposed to different redox potentials to determine shifts in both the absorption and the emission spectra of roGFP. Based on these in vitro findings, we introduce a new approach using one-wavelength excitation to use roGFP for the in vivo analysis of cell biological processes. We demonstrate the ability this technique by investigating chloroplast-located Grx1-roGFP2 expressing Arabidopsis thaliana cells as example for dynamically moving intracellular compartments. This is not possible with the two-wavelength excitation technique established so far, which hampers a quantitative analysis of highly mobile samples due to the time delay between the two measurements and the consequential displacement of the investigated area.

  3. HD 50844: a new look at δ Scuti stars from CoRoT space photometry

    NASA Astrophysics Data System (ADS)

    Poretti, E.; Michel, E.; Garrido, R.; Lefèvre, L.; Mantegazza, L.; Rainer, M.; Rodríguez, E.; Uytterhoeven, K.; Amado, P. J.; Martín-Ruiz, S.; Moya, A.; Niemczura, E.; Suárez, J. C.; Zima, W.; Baglin, A.; Auvergne, M.; Baudin, F.; Catala, C.; Samadi, R.; Alvarez, M.; Mathias, P.; Paparò, M.; Pápics, P.; Plachy, E.

    2009-10-01

    Context: Aims: This work presents the results obtained by CoRoT on HD 50844, the only δ Sct star observed in the CoRoT initial run (57.6 d). The aim of these CoRoT observations was to investigate and characterize for the first time the pulsational behaviour of a δ Sct star, when observed at a level of precision and with a much better duty cycle than from the ground. Methods: The 140 016 datapoints were analysed using independent approaches (SigSpec software and different iterative sine-wave fittings) and several checks performed (splitting of the timeseries in different subsets, investigation of the residual light curves and spectra). A level of 10-5 mag was reached in the amplitude spectra of the CoRoT timeseries. The space monitoring was complemented by ground-based high-resolution spectroscopy, which allowed the mode identification of 30 terms. Results: The frequency analysis of the CoRoT timeseries revealed hundreds of terms in the frequency range 0-30 d-1. All the cross-checks confirmed this new result. The initial guess that δ Sct stars have a very rich frequency content is confirmed. The spectroscopic mode identification gives theoretical support since very high-degree modes (up to ℓ=14) are identified. We also prove that cancellation effects are not sufficient in removing the flux variations associated to these modes at the noise level of the CoRoT measurements. The ground-based observations indicate that HD 50844 is an evolved star that is slightly underabundant in heavy elements, located on the Terminal Age Main Sequence. Probably due to this unfavourable evolutionary status, no clear regular distribution is observed in the frequency set. The predominant term (f_1=6.92 d-1) has been identified as the fundamental radial mode combining ground-based photometric and spectroscopic data. Conclusions: The CoRoT space mission was developed and is operated by the French space agency CNES, with participation of ESA's RSSD and Science Programmes, Austria

  4. CoRoT light curves of Blazhko RR Lyrae stars. Evidence of a strong correlation between phase and amplitude modulations of CoRoT ID 0105288363

    NASA Astrophysics Data System (ADS)

    Chadid, M.; Perini, C.; Bono, G.; Auvergne, M.; Baglin, A.; Weiss, W. W.; Deboscher, J.

    2011-03-01

    Context. The CoRoT - Convection Rotation and planetary Transits - space mission provides a unique opportunity to monitor RR Lyrae stars with excellent time-sampling, unprecedented photometric precision, and a long time base of 150 days. Aims: The pulsation characteristics of RR Lyrae stars rely on robust physics, but we still lack a firm quantitative understanding of the physical mechanisms driving the Blazhko modulation and the long-term changes in their pulsation behavior. We use the high-precision space data of an unknown RR Lyrae star CoRoT ID 0105288363 observed during a second long run centered on the Galaxy - LRc02 -, to improve our understanding of the pulsation properties of RR Lyrae stars. Methods: The CoRoT data were corrected using a jump and trend filtering code. We applied different period-finding techniques including Period04, MuFrAn, PDM, and SigSpec. Amplitude and phase modulation were investigated using an analytical function method as well as traditional O-C diagrams. Results: For the first time, we detect significant cycle-to-cycle changes in the Blazhko modulation, which appear to be analogous to those predicted by Stothers - owing to the suppression of turbulent convection - to explain this phenomenon. We discuss the clear correlations between the phase and the amplitude of the bump, and the skewness and acuteness of the light curve during different Blazhko cycles. We find that these quantities are strongly anticorrelated with the fundamental pulsation period. This provides a strong support to the slow convective cycle model suggested by Stothers. We also detect a long-term modulation period in the maximum brightness spectrum. A more extended coverage of the long-term modulation is required to constrain its period. Seventh-order side peaks of the pulsation multiplet structure are also visible with the left-side peak amplitudes being higher than those of the right. This has never previously been detected. Future theoretical investigations are

  5. Effects of the novel 5-HT(6) receptor antagonist RO4368554 in rat models for cognition and sensorimotor gating.

    PubMed

    Schreiber, Rudy; Vivian, Jef; Hedley, Linda; Szczepanski, Krystine; Secchi, Rob L; Zuzow, Marcus; van Laarhoven, Susanne; Moreau, Jean-Luc; Martin, James R; Sik, Ayhan; Blokland, Arjan

    2007-03-01

    Serotonin(6) (5-HT(6)) receptors are almost exclusively located in the central nervous system. High expression in the hippocampus, nucleus accumbens and striatum is consistent with a potential role in cognition and psychosis. The availability of potent, selective and brain-penetrating 5-HT(6) antagonists such as RO4368554 allows further characterization of the role of the 5-HT(6) receptor in these processes. Herein, we tested RO4368554 in several cognition tasks, as well as sensorimotor gating tests. Using scopolamine-impaired and unimpaired adult male rats, RO4368554 was given in novel object discrimination, social recognition, social discrimination, Morris water maze, passive avoidance and autoshaping procedures. RO4368554 reversed the effects of scopolamine in novel object discrimination (active doses in mg/kg, i.p., 3, 10), social recognition (3, 10), social discrimination (1, 3, 10) and passive avoidance (10, 30 i.p. and 100 p.o.) tasks. In unimpaired rats, RO4368554 enhanced object discrimination (3, 10; 4-h forgetting interval) and autoshaping learning (3), but was inactive in a water maze task (doses tested: 1-10 mg/kg, i.p.). In tests sensitive to antipsychotics, RO4368554 did not reverse sensorimotor gating deficits induced by the psychostimulants dizocilpine and amphetamine (doses tested: 1-30 mg/kg, i.p.) or neonatal lesion of the ventral hippocampus (1-10 mg/kg, i.p.). In conclusion, RO4368554 enhanced learning and memory processes in unimpaired and scopolamine-impaired rats, supporting the notion that the cognitive enhancing effects of 5-HT(6) receptor antagonists involve modulation of cholinergic neurotransmission.

  6. Characterization and biotoxicity assessment of dissolved organic matter in RO concentrate from a municipal wastewater reclamation reverse osmosis system.

    PubMed

    Sun, Ying-Xue; Gao, Yue; Hu, Hong-Ying; Tang, Fang; Yang, Zhe

    2014-12-01

    Reverse osmosis (RO) concentrate from municipal wastewater reclamation reverse osmosis (mWRRO) system containing organic compounds may associate with toxic risk, and its discharge might pose an environmental risk. To identify a basis for the selection of feasible technology in treating RO concentrates, the characteristics and biotoxicity of different fractions of dissolved organic matter (DOM) in RO concentrates from an mWRRO system were investigated. The results indicated that the hydrophilic neutrals (HIN), hydrophobic acids (HOA) and hydrophobic bases (HOB) accounted for 96% of the dissolved organic carbon (DOC) of the total DOM in the RO concentrate. According to the SEC chromatograph detected at 254 nm wavelength of UV, the DOM with molecular weight (MW) 1-3 kDa accounted for the majority of the basic and neutral fractions. The fluorescence spectra of the excitation emission matrix (EEM) indicated that most aromatic proteins, humic/fulvic acid-like and soluble microbial by-product-like substances existed in the fractions HOA and hydrophobic neutrals (HON). The genotoxicity and anti-estrogenic activity of the RO concentrate were 1795.6 ± 57.2 μg 4-NQOL(-1) and 2.19 ± 0.05 mg TAM L(-1), respectively. The HIN, HOA, and HOB contributed to the genotoxicity of the RO concentrate, and the HIN was with the highest genotoxic level of 1007.9 ± 94.8 μg 4-NQOL(-1). The HOA, HON, and HIN lead to the total anti-estrogenic activity of the RO concentrate, and HOA occupied approximately 60% of the total, which was 1.3 ± 0.17 mg TAM L(-1).

  7. Surface display of roGFP for monitoring redox status of extracellular microenvironments in Shewanella oneidensis biofilms.

    PubMed

    Sivakumar, Krishnakumar; Mukherjee, Manisha; Cheng, Hsin-I; Zhang, Yingdan; Ji, Lianghui; Cao, Bin

    2015-03-01

    Biofilms are the most ubiquitous and resilient form of microbial life on earth. One most important feature of a biofilm is the presence of a self-produced matrix, which creates highly heterogeneous and dynamic microenvironments within biofilms. Redox status in biofilm microenvironments plays a critical role in biofilm development and function. However, there is a lack of non-intrusive tools to quantify extracellular redox status of microenvironments within a biofilm matrix. In this study, using Shewanella oneidensis as a model organism, we demonstrated a novel approach to monitor extracellular redox status in biofilm microenvironments. Specifically, we displayed a redox sensitive fluorescence protein roGFP onto the cell surface of S. oneidensis by fusing it to the C-terminus of BpfA, a large surface protein, and used the surface displayed roGFP as a sensor to quantify the extracellular redox status in the matrix of S. oneidensis biofilms. The fusion of roGFP into BpfA has no negative impacts on cell growth and biofilm formation. Upon exposure to oxidizing agents such as H2 O2 , Ag(+) , and SeO3 (2-) , S. oneidensis BpfA-roGFP cells exhibited a characteristic fluorescence of roGFP. Proteinase treatment assay and super-resolution structured illumination microscopy confirmed the surface localization of BpfA-roGFP. We further used the surface displayed roGFP monitored the extracellular redox status in the matrix at different depths of a biofilm exposed to H2 O2 . This study provides a novel approach to non-invasively monitor extracellular redox status in microenvironments within biofilms, which can be used to understand redox responses of biofilms to environmental perturbations.

  8. Five Years of the RoBOT "Rocks Beneath Our Toes" High School Outreach Program

    NASA Astrophysics Data System (ADS)

    Baxter, E. F.

    2011-12-01

    The "Rocks Beneath Our Toes" or RoBOT Program began in 2006 as part of an NSF CAREER award through the Geochemistry and Petrology Program. The educational outreach program engages Boston area high school students in a hands on study of rocks and minerals collected in their communities. The goal is to provide high school students a unique window into modern scientific methods of geochemistry and mineralogy and create a higher level of interest and awareness of geoscience amongst Massachusetts secondary school students who are less often exposed to earth science coursework. Beginning with a joint field trip to sampling sites identified by participants, high school students work with Boston University undergraduates enrolled in Mineralogy to analyze their samples in thin section. During the field trip, each BU undergraduate is paired with a high school student. The assignment of student pairings (started in year 2) dramatically increased student interactions and enjoyment. The program culminates with a visit by the high school group to tour BU's lab facilities and work with the undergraduates using the petrographic microscopes to explore their rock. At this visit, BU undergraduates present their semester's work in one-on-one powerpoint presentations from which discussion and microscope work follow. Thus far, >50 high school students, >40 undergraduates, and 7 high school educators were involved in the program. This included participants from three different suburban Boston area high schools and with students enrolled in the BU "Upward Bound" program: an existing program designed to enhance educational opportunities for Boston inner city high school students. Participant reviews indicate great success in achieving the program's goals. Notably, both BU undergraduates and high school students rated the opportunities for interaction with eachother among the best aspects of RoBOT. On a scale of 1 to 10, BU undergraduates rated the following four categories highest

  9. New RoF-PON architecture using polarization multiplexed wireless MIMO signals for NG-PON

    NASA Astrophysics Data System (ADS)

    Elmagzoub, M. A.; Mohammad, Abu Bakar; Shaddad, Redhwan Q.; Al-Gailani, Samir A.

    2015-06-01

    Next-generation access networks require provision of wireless services and high data rate to meet the huge demands for mobility and multiple services. Moreover, reusing the currently deployed optical distribution networks (ODNs) is highly beneficial and cost effective for providing the new high data rate wireless demands. In this paper, bidirectional radio over fiber passive optical network (RoF-PON) capable of handling multiple-input-multiple-output (MIMO) streams at low cost, high spectral efficiency and backward compatibility with currently deployed PON, is proposed. To the best of our knowledge, all the existing RoF MIMO solutions have not considered compatibility with currently deployed ODNs. Eight laser diodes (LDs) at the central office (CO) are enough for the whole system, instead of having LD or optical transmitter at each remote antenna unit (RAU), which makes a colorless and cost-effective RAU. Twenty four wavelengths are generated using optical comb technique. Each two 16-QAM MIMO signals that have the same carrier frequency in the downstream (DS) transmission are optically combined using polarization-division-multiplexing (PDM), where each two upstream (US) MIMO signals are time division multiplexed. The PDM configuration doubles spectral efficiency with a power penalty of only 1.5 dB. The proposed architecture is a bidirectional asymmetric RoF-PON with total 40/10 Gb/s for DS/US transmission. Even after transmission over 20 km SMF and splitting ratio of 32, acceptable transmission performance and widely separated constellation diagrams for the 16-QAM signals are achieved, with bit error rate (BER) of 10-6 for DS signals and 10-3 for the US signals which can be reduced down to 10-6 by using forward error correction (FEC).

  10. Potential Return on Investment (RoI) on web-based diabetes education in UK.

    PubMed

    Shabestari, Omid; Roudsari, Abdul

    2009-01-01

    The incidence of diabetes mellitus is growing in the UK. As most diabetes care is performed by the patients themselves, structured education is one way to encourage their responsible participation in delivering effective care. Continuous e-learning by Internet has proven to be a useful method of diabetes education. "Return on Investment" (RoI) can be used as an indicator of the cost-benefit of web-based education. RoI is the ratio of money gained or lost on an investment relative to the amount of money invested. This report uses system dynamics modeling to predict the flow of patients in the educational system and the cost of their care. The analysis compared traditional and web-based education. Separate models were developed for each educational method and simulated until 2020 in one year intervals. The population of diabetic patients was adjusted at each cycle according to anticipated incidence and mortality rates. The population of educated diabetic patients was based on the educational capacity and literacy limits of each method. A report by the National Health Service (NHS) was used to calculate the cost of care by considering the cost difference between uneducated and educated patients. By 2020 with an annual rate of inflation of 3%, the annual cost of care is projected to increase to pound 3.67 billion for the traditional model as compared to pound 3.39 billion for the web-based model. RoI is estimated to be a ratio of 32.33. Investment in web-based diabetes education is not only a health benefit but also a reduction in care cost.

  11. Proton pump inhibitors

    MedlinePlus

    Proton pump inhibitors (PPIs) are medicines that work by reducing the amount of stomach acid made by ... Proton pump inhibitors are used to: Relieve symptoms of acid reflux, or gastroesophageal reflux disease (GERD). This ...

  12. Rotation period distribution of CoRoT and Kepler Sun-like stars

    NASA Astrophysics Data System (ADS)

    Leão, I. C.; Pasquini, L.; Ferreira Lopes, C. E.; Neves, V.; Valcarce, A. A. R.; de Oliveira, L. L. A.; Freire da Silva, D.; de Freitas, D. B.; Canto Martins, B. L.; Janot-Pacheco, E.; Baglin, A.; De Medeiros, J. R.

    2015-10-01

    Aims: We study the distribution of the photometric rotation period (Prot), which is a direct measurement of the surface rotation at active latitudes, for three subsamples of Sun-like stars: one from CoRoT data and two from Kepler data. For this purpose, we identify the main populations of these samples and interpret their main biases specifically for a comparison with the solar Prot. Methods: Prot and variability amplitude (A) measurements were obtained from public CoRoT and Kepler catalogs, which were combined with public data of physical parameters. Because these samples are subject to selection effects, we computed synthetic samples with simulated biases to compare with observations, particularly around the location of the Sun in the Hertzsprung-Russel (HR) diagram. Publicly available theoretical grids and empirical relations were used to combine physical parameters with Prot and A. Biases were simulated by performing cutoffs on the physical and rotational parameters in the same way as in each observed sample. A crucial cutoff is related with the detectability of the rotational modulation, which strongly depends on A. Results: The synthetic samples explain the observed Prot distributions of Sun-like stars as having two main populations: one of young objects (group I, with ages younger than ~1 Gyr) and another of main-sequence and evolved stars (group II, with ages older than ~1 Gyr). The proportions of groups I and II in relation to the total number of stars range within 64-84% and 16-36%, respectively. Hence, young objects abound in the distributions, producing the effect of observing a high number of short periods around the location of the Sun in the HR diagram. Differences in the Prot distributions between the CoRoT and Kepler Sun-like samples may be associated with different Galactic populations. Overall, the synthetic distribution around the solar period agrees with observations, which suggests that the solar rotation is normal with respect to Sun

  13. Reassessing the radial-velocity evidence for planets around CoRoT-7

    NASA Astrophysics Data System (ADS)

    Pont, Frédéric; Aigrain, Suzanne; Zucker, Shay

    2011-03-01

    CoRoT-7 is an 11 th magnitude K-star whose light curve shows transits with a depth of 0.3 mmag and a period of 0.854 d, superimposed on variability at the 1 per cent level, due to the modulation of evolving active regions with the star's 23-d rotation period. In this paper, we revisit the published HARPS radial-velocity (RV) measurements of the object, which were previously used to estimate the companion mass, but have been the subject of ongoing debate. We build a realistic model of the star's activity during the HARPS observations, by fitting simultaneously the linewidth (as measured by the width of the cross-correlation function) and the line bisector, and use it to evaluate the contribution of activity to the RV variations. The data show clear evidence of errors above the level of the formal uncertainties, which are accounted for neither by activity nor by any plausible planet model and which increase rapidly with a decreasing signal-to-noise ratio (S/N) of the spectra. We cite evidence of similar systematics in mid-S/N spectra of other targets obtained with HARPS and other high-precision RV spectrographs, and discuss possible sources. Allowing for these, we re-evaluate the semi-amplitude of the CoRoT-7b signal, finding Kb= 1.6 ± 1.3 m s-1, a tentative detection with a much reduced significance (1.2σ) compared to previous estimates. We also argue that the combined presence of activity and additional errors precludes a meaningful search for additional low-mass companions, despite previous claims to the contrary. Taken at face value, our analysis points to a lower density for CoRoT-7b, the 1σ mass range spanning 1-4 M ⊕ and allowing for a wide range of bulk compositions. In particular, an ice-rich composition is compatible with the RV constraints. More generally, this study highlights the importance of a realistic treatment of both activity and uncertainties, particularly in the medium S/N regime, which applies to most small planet candidates from CoRoT and

  14. roAp stars: surface lithium abundance distribution and magnetic field configuration

    NASA Astrophysics Data System (ADS)

    Polosukhina, N.; Shulyak, D.; Shavrina, A.; Lyashko, D.; Drake, N. A.; Glagolevski, Yu.; Kudryavtsev, D.; Smirnova, M.

    2014-08-01

    High-resolution spectra obtained with the 6m BTA telescope, Russia, and with HARPS and VLT/UVES telescopes at ESO, Chile, were used for Doppler Imaging analysis of two roAp stars, HD 12098 and HD 60435, showing strong and variable Li resonance line in their spectra. We found that Li has highly inhomogeneous distribution on the surfaces of these stars. We compared our results with previously obtained Doppler Imaging mapping of two CP2 stars, HD 83368 and HD 3980, and discuss the correlation between the position of the high Li-abundance spots and magnetic field.

  15. Preclinical and Early Clinical Profile of a Highly Selective and Potent Oral Inhibitor of Aldosterone Synthase (CYP11B2)

    PubMed Central

    Schwab, Dietmar; Delporte, Marie-Laure; Palermo, Giuseppe; Amrein, Kurt; Mohr, Susanne; De Vera Mudry, Maria Cristina; Brown, Morris J.; Ferber, Philippe

    2017-01-01

    Primary hyperaldosteronism is a common cause of resistant hypertension. Aldosterone is produced in the adrenal by aldosterone synthase (AS, encoded by the gene CYP11B2). AS shares 93% homology to 11β-hydroxylase (encoded by the gene CYP11B1), responsible for cortisol production. This homology has hitherto impeded the development of a drug, which selectively suppresses aldosterone but not cortisol production, as a new treatment for primary hyperaldosteronism. We now report the development of RO6836191 as a potent (Ki 13 nmol/L) competitive inhibitor of AS, with in vitro selectivity >100-fold over 11β-hydroxylase. In cynomolgus monkeys challenged with synthetic adrenocorticotropic hormone, single doses of RO6836191 inhibited aldosterone synthesis without affecting the adrenocorticotropic hormone–induced rise in cortisol. In repeat-dose toxicity studies in monkeys, RO6836191 reproduced the adrenal changes of the AS−/− mouse: expansion of the zona glomerulosa; increased expression of AS (or disrupted green fluorescent protein gene in the AS−/− mouse); hypertrophy, proliferation, and apoptosis of zona glomerulosa cells. These changes in the monkey were partially reversible and partially preventable by electrolyte supplementation and treatment with an angiotensin-converting enzyme inhibitor. In healthy subjects, single doses of RO6836191, across a 360-fold dose range, reduced plasma and urine aldosterone levels with maximum suppression at a dose of 10 mg, but unchanged cortisol, on adrenocorticotropic hormone challenge, up to 360 mg, and increase in the precursors 11-deoxycorticosterone and 11-deoxycortisol only at or >90 mg. In conclusion, RO6836191 demonstrates that it is possible to suppress aldosterone production completely in humans without affecting cortisol production. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT01995383. PMID:27872236

  16. Li and Ag Co-Doped ZnO Photocatalyst for Degradation of RO 4 Dye Under Solar Light Irradiation.

    PubMed

    Dhatshanamurthi, P; Shanthi, M

    2016-06-01

    The synthesis of Li doped Ag-ZnO (Li-Ag-ZnO) has been successfully achieved by a sonochemically assisted precipitation-decomposition method. The synthesized catalyst was characterized by X-ray diffraction (XRD), transmission electron microscopy (TEM), field emission scanning electron microscopy (FE-SEM), energy dispersive spectroscopy (EDS), diffuse reflectance spectra (DRS), photoluminescence spectra (PL), X-ray photoelectron spectra (XPS) and BET surface area measurements. The photocatalytic activity of Li-Ag-ZnO was investigated for the degradation of Reactive orange 4 (RO 4) dye in aqueous solution under solar light irradiation. Co-dopants shift the absorbance of ZnO to the visible region. Li-Ag-ZnO is found to be more efficient than Ag-ZnO, Li-ZnO, commercial ZnO and prepared ZnO at pH 7 for the mineralization of RO 4 dye under solar light irradiation. The influences of operational parameters such as the amount of photocatalyst, dye concentration, initial pH on photo-mineralization of RO 4 have been analyzed. The mineralization of RO 4 dye has been confirmed by COD measurements. A degradation mechanism is proposed for the degradation of RO 4 under solar light. The catalyst was found to be more stable and reusable.

  17. Refractory depression: mechanisms and evaluation of radically open dialectical behaviour therapy (RO-DBT) [REFRAMED]: protocol for randomised trial

    PubMed Central

    Lynch, T R; Whalley, B; Hempel, R J; Byford, S; Clarke, P; Clarke, S; Kingdon, D; O'Mahen, H; Russell, I T; Shearer, J; Stanton, M; Swales, M; Watkins, A; Remington, B

    2015-01-01

    Introduction Only 30–40% of depressed patients treated with medication achieve full remission. Studies that change medication or augment it by psychotherapy achieve only limited benefits, in part because current treatments are not designed for chronic and complex patients. Previous trials have excluded high-risk patients and those with comorbid personality disorder. Radically Open Dialectical Behaviour Therapy (RO-DBT) is a novel, transdiagnostic treatment for disorders of emotional over-control. The REFRAMED trial aims to evaluate the effectiveness and cost-effectiveness of RO-DBT for patients with treatment-resistant depression. Methods and analysis REFRAMED is a multicentre randomised controlled trial, comparing 7 months of individual and group RO-DBT treatment with treatment as usual (TAU). Our primary outcome measure is depressive symptoms 12 months after randomisation. We shall estimate the cost-effectiveness of RO-DBT by cost per quality-adjusted life year. Causal analyses will explore the mechanisms by which RO-DBT is effective. Ethics and dissemination The National Research Ethics Service (NRES) Committee South Central – Southampton A first granted ethical approval on 20 June 2011, reference number 11/SC/0146. Trial registration number ISRCTN85784627. PMID:26187121

  18. The study of CD20 and CD45.Ro antibodies in the inflammatory infiltrate involved in acne and seborrheic dermatitis.

    PubMed

    Ianoşi, Simona; Stoicescu, Irina; Ianoşi, G; Neagoe, Daniela; Georgescu, Claudia Valentina

    2007-01-01

    The aim of our study was to evaluate the role of CD20 and CD45.Ro antibodies in acne and seborrheic dermatitis. A number of 20 patients with papular, pustular or nodular acne and another 20 patients with seborrheic dermatitis were available for our study. We removed bioptic material from all of them and we perform histochemical and immunohistochemical processing within the Laboratory of Histology, Histopathology and Immunohistochemistry of the University of Medicine and Pharmacy of Craiova. In acne, we could reveal a positive CD45.Ro immunomarking in rare lymphoid cells situated in the middle derma at a distance from the affected pilosebaceous follicle and in the inflammatory infiltrate subepidermically, and also a negative immunomarking in the inflammatory cells from the proximity of the affected pilosebaceous follicle. In patients with seborrheic dermatitis we noticed a positive immunomarking infiltrate of the papillary derma and a positive immunomarking of membrane for CD45.Ro in many lymphoid cells of the inflammatory infiltrate situated in the papillary derma predominantly disposed perivasculary. Conclusions. The absence of the cells marked with CD45.Ro in the proximity of the pilosebaceous follicle interested in acne excludes the direct participation of B- and T-lymphocytes in the perifollicular inflammatory process, though the T-lymphocytes can be revealed in a small number at a distance from the affected follicle. The inflammatory infiltrate from the seborrheic dermatitis proved to be rich in positive CD45.Ro cells and poorer in positive CD20 cells.

  19. A new approach for determination of fouling potential by colloidal nanoparticles during reverse osmosis (RO) membrane filtration of seawater

    NASA Astrophysics Data System (ADS)

    Park, Ji Yeon; Lim, Sungil; Park, Kihong

    2013-04-01

    A direct measurement of number concentration of colloidal nanoparticles (15-450 nm) in water was made with the membrane filtration-differential mobility analyzer technique, and its corresponding flux decline rate (FDR) was determined by laboratory-scale RO fouling test unit using varying number concentrations of silica nanoparticles in artificial seawaters. This relationship was used to predict fouling potential of colloidal nanoparticles in reverse osmosis (RO) membrane process of seawaters in RO plant. It was found that the FDR linearly increased with the increasing number of colloidal nanoparticles for the given concentration range and that the relationship between the number concentration and the FDR also depended on RO membrane surface properties. Data for estimated FDR values for natural seawaters after pretreatment showed a clear difference among samples, which is contrary to the pre-existing index such as silt density index and modified fouling index. Our data suggest that measurement of colloidal nanoparticles is useful for selection of proper pretreatment and successful operation of RO membrane process along with other particle fouling predictors accounting for large particles (>450 nm).

  20. BCFtools/RoH: a hidden Markov model approach for detecting autozygosity from next-generation sequencing data

    PubMed Central

    Narasimhan, Vagheesh; Danecek, Petr; Scally, Aylwyn; Xue, Yali; Tyler-Smith, Chris; Durbin, Richard

    2016-01-01

    Summary: Runs of homozygosity (RoHs) are genomic stretches of a diploid genome that show identical alleles on both chromosomes. Longer RoHs are unlikely to have arisen by chance but are likely to denote autozygosity, whereby both copies of the genome descend from the same recent ancestor. Early tools to detect RoH used genotype array data, but substantially more information is available from sequencing data. Here, we present and evaluate BCFtools/RoH, an extension to the BCFtools software package, that detects regions of autozygosity in sequencing data, in particular exome data, using a hidden Markov model. By applying it to simulated data and real data from the 1000 Genomes Project we estimate its accuracy and show that it has higher sensitivity and specificity than existing methods under a range of sequencing error rates and levels of autozygosity. Availability and implementation: BCFtools/RoH and its associated binary/source files are freely available from https://github.com/samtools/BCFtools. Contact: vn2@sanger.ac.uk or pd3@sanger.ac.uk Supplementary information: Supplementary data are available at Bioinformatics online. PMID:26826718

  1. Muscarinic type 3 receptor autoantibodies are associated with anti-SSA/Ro autoantibodies in Sjögren’s syndrome

    PubMed Central

    Zuo, Jian; Williams, Adrienne E.G.; Park, Yun-Jong; Choi, Kevin; Chan, Annie L.; Reeves, Westley H.; Bubb, Michael R.; Lee, Yun Jong; Park, Kyungpyo; Stewart, Carol M.; Cha, Seunghee

    2016-01-01

    Anti-muscarinic type 3 receptor autoantibodies (anti-M3R) are reported as potential inhibitors of saliva secretion in Sjögren’s syndrome (SjS). However, despite extensive efforts to establish an anti-M3R detection method, there is no clinical test available for these autoantibodies. The purpose of this study was to propose inclusion of anti-M3R testing for SjS diagnosis through investigation of their prevalence using a modified In-Cell Western (ICW) assay. A stable cell line expressing human M3R tagged with GFP (M3R-GFP) was established to screen unadsorbed and adsorbed plasma from primary SjS (n = 24), rheumatoid arthritis (RA, n = 18), systemic lupus erythematosus (SLE, n = 18), and healthy controls (HC, n = 23). Anti-M3R abundance was determined by screening for the intensity of human IgG interacting with M3R-GFP cells by ICW assay, as detected by an anti-human IgG IRDye800-conjugated secondary antibody and normalized to GFP. Method comparisons and receiver-operating-characteristic (ROC)-curve analyses were performed to evaluate the diagnostic value of our current approaches. Furthermore, clinical parameters of SjS were also analyzed in association with anti-M3R. Anti-M3R was significantly elevated in SjS plasma in comparison with HC, SLE, or RA (P < 0.01). SjS anti-M3R intensities were greater than two-standard deviations above the HC mean for both unadsorbed (16/24, 66.67%) and adsorbed (18/24, 75%) plasma samples. Furthermore, anti-M3R was associated with anti-SjS-related-antigen A/Ro positivity (P = 0.0353). Linear associations for anti-M3R intensity indicated positive associations with focus score (R2 = 0.7186, P < 0.01) and negative associations with saliva flow rate (R2 = 0.3052, P < 0.05). Our study strongly supports our rationale to propose inclusion of anti-M3R for further testing as a non-invasive serological marker for SjS diagnosis. PMID:27460476

  2. Ab initio ro-vibronic spectroscopy of SiCCl (X{sup ~2}Π)

    SciTech Connect

    Brites, Vincent; Mitrushchenkov, Alexander O.; Léonard, Céline; Peterson, Kirk A.

    2014-07-21

    The full dimensional potential energy surfaces of the {sup 2}A{sup ′} and {sup 2}A{sup ′′} electronic components of X{sup ~2}Π SiCCl have been computed using the explicitly correlated coupled cluster method, UCCSD(T)-F12b, combined with a composite approach taking into account basis set incompleteness, core-valence correlation, scalar relativity, and higher order excitations. The spin-orbit and dipole moment surfaces have also been computed ab initio. The ro-vibronic energy levels and absorption spectrum at 5 K have been determined from variational calculations. The influence of each correction on the fundamental frequencies is discussed. An assignment is proposed for bands observed in the LIF experiment of Smith et al. [J. Chem. Phys. 117, 6446 (2002)]. The overall agreement between the experimental and calculated ro-vibronic levels is better than 7 cm{sup −1} which is comparable with the 10–20 cm{sup −1} resolution of the emission spectrum.

  3. Effects of cefetamet (Ro 15-8074) on Treponema pallidum and experimental syphilis.

    PubMed Central

    Fitzgerald, T J

    1992-01-01

    Cefetamet pivoxil (Ro 15-8075) is a newly developed, expanded-spectrum cephalosporin that is orally active. In vitro, the active form, cefetamet (Ro 15-8074), at a concentration of 0.05 micrograms/ml killed and lysed Treponema pallidum. Rabbit serum did not diminish its effectiveness. The antibiotic rapidly entered the circulation following intramuscular injection into rabbits, attaining its highest levels of 24 to 37 micrograms/ml within 10 to 30 min. Animals were infected intradermally with T. pallidum and then treated with different doses of cefetamet. Accelerated healing was detected following treatment with 15 and 30 mg/kg of body weight. The antibiotic was also effective in killing organisms that had disseminated to distant tissues. In three separate sets of experiments, rabbits were infected with treponemes and then treated with cefetamet intramuscularly at 1, 15, or 30 mg/kg as follows: (i) after lesions had just become clinically apparent, (ii) after lesions were enlarged and well developed, or (iii) prior to the appearance of clinical lesions. Antibiotic effectiveness was determined by sacrificing the animals 1 week after antibiotic treatment and examining splenic tissue for residual, disseminated treponemes. Cefetamet was treponemicidal in all three situations. Maximum effects occurred when the antibiotic was injected before lesions had become clinically apparent (incubation period). These results suggest that cefetamet pivoxil might be useful for treating syphilitic infections. PMID:1622168

  4. Isolated Ro52 Antibodies as Immunological Marker of a Mild Phenotype of Undifferentiated Connective Tissue Diseases

    PubMed Central

    Navarro-Gonzálvez, José Antonio; Rodríguez-Lozano, Beatriz

    2017-01-01

    The term undifferentiated connective tissue disease (UCTD) is used to describe undiagnosed patients that do not fulfill classification criteria for definite connective tissue disease (Systemic Lupus, Systemic Sclerosis, Sjögren Syndrome, and Dermatomyositis/Polymyositis). It is important to find serological markers as predictors of the evolution or severity of these diseases. The objective of this retrospective study was to investigate if there was a milder subgroup of UCTD with a special clinical profile consisting only in the presence of anti-Ro52 autoantibodies. Immunological and clinical records of 62 patients attending the hospital during 30 months were studied. Results showed a target population formed by mostly women, aged between 40 and 80 years at the moment of the study, with a registered age of onset between 40 and 60 years. Speckled pattern was the most frequent pattern found by indirect immunofluorescence. Given the obtained results and keeping in mind possible limitations because of sample size, isolated positive anti-Ro52 autoantibodies seem to lead to a benign effect in terms of evolution of the disease. As a future objective, the follow-up of these patients should be necessary to investigate new clinical symptoms, serological markers, or development of a definite connective tissue disease over time. PMID:28210273

  5. Overlap of Doxycycline Fluorescence with that of the Redox-Sensitive Intracellular Reporter roGFP.

    PubMed

    Khader, Heba; Solodushko, Victor; Al-Mehdi, Abu Bakr; Audia, Jonathon; Fouty, Brian

    2014-03-01

    Tetracycline-inducible systems allow for either suppression or induction of transgene expression to facilitate studies of cell physiology. Doxycycline is a preferred inducer for these gene expression systems due to its membrane permeability; however, the heterocyclic structure of doxycycline exhibits fluorogenic properties that can potentially bias measurement of other fluorochromes. Thus the simultaneous use of tetracycline-inducible systems and fluorescent proteins as reporter genes or as intracellular biosensors may lead to potentially confounding results. Herein, using cells which co-express the ratiometric redox sensitive intracellular reporter, roGFP, and a tetracycline-inducible reporter plasmid encoding the reporter gene, mCherry, as a model system, we describe the overlapping intracellular fluorescent signals between doxycycline and commonly used intracellular fluorescent probes. In our cells, the addition of doxycycline to cells caused a dose- and time-dependent increase in cell fluorescence with 405 nm excitation which overlapped with that of the oxidized configuration of roGFP. Incubating cells in concentrations of doxycycline less than 1 μg/mL and removing doxycycline from the media 60 min before performing experiments eliminated fluorescence interference while still maintaining maximal reporter transgene activation.

  6. RO concentrate minimization by electrodialysis: techno-economic analysis and environmental concerns.

    PubMed

    Zhang, Yang; Ghyselbrecht, Karel; Vanherpe, Ruben; Meesschaert, Boudewijn; Pinoy, Luc; Van der Bruggen, Bart

    2012-09-30

    This paper presents a systematic techno-economical analysis and an environmental impact evaluation of a reverse osmosis (RO) concentrate treatment process using electrodialysis (ED) in view of environmental management of brine discharges. The concentrate originates from a secondary effluent treated by RO. Without any treatment, the concentrate would have to be discharged; this is compared in this study to the costs and benefits of an effective treatment method in a pilot scale ED plant. A technical analysis was done both on lab scale and pilot scale for the determination of operational and maintenance costs for the ED installation at the required conditions of process performance and safety. Subsequently, an economical analysis was done to calculate the cost of the different parts of the ED system. It was shown that an operational cost of 0.19 EUR m(-3) can be achieved, assuming that the ED concentrate is to decarbonated at pH 6.0 to prevent membrane scaling. Finally, environmental impact issues were calculated and discussed for the overall system. Results imply that if renewable energy is applied for the ED power source, CO(2) emission from membrane processes can be much less than from the conventional treatment methods.

  7. Simultaneous manipulation and observation of multiple ro-vibrational eigenstates in solid para-hydrogen

    NASA Astrophysics Data System (ADS)

    Katsuki, Hiroyuki; Ohmori, Kenji

    2016-09-01

    We have experimentally performed the coherent control of delocalized ro-vibrational wave packets (RVWs) of solid para-hydrogen (p-H2) by the wave packet interferometry (WPI) combined with coherent anti-Stokes Raman scattering (CARS). RVWs of solid p-H2 are delocalized in the crystal, and the wave function with wave vector k ˜ 0 is selectively excited via the stimulated Raman process. We have excited the RVW twice by a pair of femtosecond laser pulses with delay controlled by a stabilized Michelson interferometer. Using a broad-band laser pulse, multiple ro-vibrational states can be excited simultaneously. We have observed the time-dependent Ramsey fringe spectra as a function of the inter-pulse delay by a spectrally resolved CARS technique using a narrow-band probe pulse, resolving the different intermediate states. Due to the different fringe oscillation periods among those intermediate states, we can manipulate their amplitude ratio by tuning the inter-pulse delay on the sub-femtosecond time scale. The state-selective manipulation and detection of the CARS signal combined with the WPI is a general and efficient protocol for the control of the interference of multiple quantum states in various quantum systems.

  8. Isolated anti-Ro/SSA thrombocytopenia: a rare feature of neonatal lupus.

    PubMed

    Ayadi, Imene Dahmane; Ben Hamida, Emira; Boukhris, Mohamed Riadh; Bezzine, Ahlem; Chaouachi, Sihem; Marrakchi, Zahra

    2015-01-01

    We report a rare case of isolated thrombocytopenia related to anti-Ro/SSA antibodies. The mother was followed for unlabeled familial thrombocytopenia. The mother had positive anti-Ro/SSA antibodies. She was asymptomatic without skin lesions or other criteria neither of systemic lupus erythematosus nor other connective tissue disease. Pregnancy was uneventful. The postnatal examination was normal. On the first day of life, blood cells count showed thrombocytopenia at 40 x 10(9)/L. Within the second day of life, platelet level dropped to 20 x 10(9)/L. The management of thrombocytopenia included platelet transfusion and human immunoglobulin infusion. On the fifth day of life, there has been a drop in platelet count to 10 x 10(9)/L requiring renewed platelet transfusion and human immunoglobulin infusion. On the 10(th) of life platelets rate was stable around 60 x 10(9)/L. The infant had no evidence of cardiac, dermatologic or hepatobilary involvement initially or throughout follow up.

  9. Tailoring the structure of thin film nanocomposite membranes to achieve seawater RO membrane performance.

    PubMed

    Lind, Mary Laura; Eumine Suk, Daniel; Nguyen, The-Vinh; Hoek, Eric M V

    2010-11-01

    Herein we report on the formation and characterization of pure polyamide thin film composite (TFC) and zeolite-polyamide thin film nanocomposite (TFN) reverse osmosis (RO) membranes. Four different physical-chemical post-treatment combinations were applied after the interfacial polymerization reaction to change the molecular structure of polyamide and zeolite-polyamide thin films. Both TFC and TFN hand-cast membranes were more permeable, hydrophilic, and rough than a commercial seawater RO membrane. Salt rejection by TFN membranes was consistently below that of hand-cast TFC membranes; however, two TFN membranes exhibited 32 g/L NaCl rejections above 99.4%, which was better than the commercial membrane under the test conditions employed. The nearly defect-free TFN films that produced such high rejections were achieved only with wet curing, regardless of other post-treatments. Polyamide films formed in the presence of zeolite nanoparticles were less cross-linked than similarly cast pure polyamide films. At the very low nanoparticle loadings evaluated, differences between pure polyamide and zeolite-polyamide membrane water and salt permeability correlated weakly with extent of cross-linking of the polyamide film, which suggests that defects and molecular-sieving largely govern transport through zeolite-polyamide thin film nanocomposite membranes.

  10. Transiting exoplanets from the CoRoT space mission. XI. CoRoT-8b: a hot and dense sub-Saturn around a K1 dwarf

    NASA Astrophysics Data System (ADS)

    Bordé, P.; Bouchy, F.; Deleuil, M.; Cabrera, J.; Jorda, L.; Lovis, C.; Csizmadia, S.; Aigrain, S.; Almenara, J. M.; Alonso, R.; Auvergne, M.; Baglin, A.; Barge, P.; Benz, W.; Bonomo, A. S.; Bruntt, H.; Carone, L.; Carpano, S.; Deeg, H.; Dvorak, R.; Erikson, A.; Ferraz-Mello, S.; Fridlund, M.; Gandolfi, D.; Gazzano, J.-C.; Gillon, M.; Guenther, E.; Guillot, T.; Guterman, P.; Hatzes, A.; Havel, M.; Hébrard, G.; Lammer, H.; Léger, A.; Mayor, M.; Mazeh, T.; Moutou, C.; Pätzold, M.; Pepe, F.; Ollivier, M.; Queloz, D.; Rauer, H.; Rouan, D.; Samuel, B.; Santerne, A.; Schneider, J.; Tingley, B.; Udry, S.; Weingrill, J.; Wuchterl, G.

    2010-09-01

    Aims: We report the discovery of CoRoT-8b, a dense small Saturn-class exoplanet that orbits a K1 dwarf in 6.2 days, and we derive its orbital parameters, mass, and radius. Methods: We analyzed two complementary data sets: the photometric transit curve of CoRoT-8b as measured by CoRoT and the radial velocity curve of CoRoT-8 as measured by the HARPS spectrometer. Results: We find that CoRoT-8b is on a circular orbit with a semi-major axis of 0.063 ± 0.001 AU. It has a radius of 0.57 ± 0.02 RJ, a mass of 0.22 ± 0.03 MJ, and therefore a mean density of 1.6 ± 0.1 g cm-3. Conclusions: With 67% of the size of Saturn and 72% of its mass, CoRoT-8b has a density comparable to that of Neptune (1.76 g cm-3). We estimate its content in heavy elements to be 47-63 {M}_⊕, and the mass of its hydrogen-helium envelope to be 7-23 {M}_⊕. At 0.063 AU, the thermal loss of hydrogen of CoRoT-8b should be no more than 0.1% over an assumed integrated lifetime of 3 Ga. Observations made with SOPHIE spectrograph at Observatoire de Haute Provence, France (PNP.07B.MOUT), and the HARPS spectrograph at ESO La Silla Observatory (081.C-0388 and 083.C-0186). The CoRoT space mission, launched on December 27, 2006, has been developed and is operated by the CNES with the contribution of Austria, Belgium, Brasil, ESA, Germany, and Spain.Both data sets are available in electronic form at the CDS via anonymous ftp to cdsarc.u-strasbg.fr (130.79.128.5) or via http://cdsarc.u-strasbg.fr/viz-bin/qcat?J/A+A/520/A66

  11. A Single-Chip Speech Dialogue Module and Its Evaluation on a Personal Robot, PaPeRo-Mini

    NASA Astrophysics Data System (ADS)

    Sato, Miki; Iwasawa, Toru; Sugiyama, Akihiko; Nishizawa, Toshihiro; Takano, Yosuke

    This paper presents a single-chip speech dialogue module and its evaluation on a personal robot. This module is implemented on an application processor that was developed primarily for mobile phones to provide a compact size, low power-consumption, and low cost. It performs speech recognition with preprocessing functions such as direction-of-arrival (DOA) estimation, noise cancellation, beamforming with an array of microphones, and echo cancellation. Text-to-speech (TTS) conversion is also equipped with. Evaluation results obtained on a new personal robot, PaPeRo-mini, which is a scale-down version of PaPeRo, demonstrate an 85% correct rate in DOA estimation, and as much as 54% and 30% higher speech recognition rates in noisy environments and during robot utterances, respectively. These results are shown to be comparable to those obtained by PaPeRo.

  12. Computing Ro in a population with heterogeneity in sexual activity and proportionate mixing using a STM-solver

    NASA Astrophysics Data System (ADS)

    Gutierrez A., Natalia A.

    2014-06-01

    A model to determinate the reproductive basic number, detonated Ro, for the case of population with heterogeneity in sexual activity and proportionate mixing is solved using computer algebra and SMT solvers. Specifically Maple and Z3 were used. The code for the solution of the model was written in Z3-Python, but it can also be played by Z3-SMT-Lib. Ro represents an algebraic synthesis of every epidemiological parameter. Numerical simulations were done to prove the effectiveness of the model and the code. The algebraic structure of Ro suggests the possible control measurements that should be implemented to avoid the propagation of the sexual transmitted diseases. The obtained results are important on the computational epidemiology field. As a future investigation, it is suggested to apply the STM solvers to analyze models for other kinds of epidemic diseases.

  13. Diazepam-induced release of behavior in an extinction procedure: its reversal by Ro 15-1788.

    PubMed

    Thiébot, M H; Childs, M; Soubrié, P; Simon, P

    1983-03-18

    The effects of the benzodiazepine receptor antagonist Ro 15-1788, an imidazobenzodiazepine derivative, were studied with respect to three pharmacological activities exerted by diazepam in rats. Two of these, release of shock-induced suppression of drinking and attenuation of non-reward-induced cessation of responding for food, reflect the anxiolytic property of benzodiazepines. The amnesic-like effect of diazepam was also investigated. Ro 15-1788 (in doses ranging from 4 to 16 mg/kg p.o.) completely reversed diazepam (2 mg/kg)-induced release of behavior in both punishment and non-reward procedures. In contrast, Ro 15-1788 reduced but did not completely abolish diazepam-induced amnesia. These data suggest that the anticonflict and anti-frustration effects of benzodiazepines probably involve similar receptor types which nevertheless differ from those chiefly implicated in the amnesic-like activity of benzodiazepines.

  14. Benzodiazepine receptor inverse agonists. beta. -CCM and RO 15-3505 both reverse the anxiolytic effects of ethanol in mice

    SciTech Connect

    Belzung, C.; Misslin, R.; Vogel, E.

    1988-01-01

    The antagonistic effects of the benzodiazepine receptor inverse agonist ..beta..-CCM and of the partial inverse agonist RO 15-3505 on the anxiolytic properties of ethanol in mice confronted with a light/dark choice procedure and with the staircase test were investigated. Both drugs reversed the effects of ethanol on some of the behavioral parameters, but ..beta..-CCM alone elicited anxiogenic intrinsic effects. RO-3505 induced seizures in mice treated with a subconvulsant dose of pentylenetetrazole, the most efficient doses being 3 and 6 mg/kg. These data indicate that ..beta..-CCM and RO 15-3505 can reverse some of the anxiolytic effects of ethanol, acting probably to oppose GABA function via the benzodiazepine receptor.

  15. Modulation of cholinephosphotransferase activity in breast cancer cell lines by Ro5-4864, a peripheral benzodiazepine receptor agonist

    SciTech Connect

    Akech, Jacqueline; Roy, Somdutta Sinha; Das, Salil K. . E-mail: sdas@mmc.edu

    2005-07-22

    Changes in phospholipid and fatty acid profile are hallmarks of cancer progression. Increase in peripheral benzodiazepine receptor expression has been implicated in breast cancer. The benzodiazepine, Ro5-4864, increases cell proliferation in some breast cancer cell lines. Biosynthesis of phosphatidylcholine (PC) has been identified as a marker for cells proliferating at high rates. Cholinephosphotransferase (CPT) is the terminal enzyme for the de novo biosynthesis of PC. We have addressed here whether Ro5-4864 facilitates some cancer causing mechanisms in breast cancer. We report that cell proliferation increases exponentially in aggressive breast cancer cell lines 11-9-1-4 and BT-549 when treated with nanomolar concentrations of Ro5-4864. This increase is seen within 24 h of treatment, consistent with the cell doubling time in these cells. Ro5-4864 also upregulates c-fos expression in breast cancer cell lines 11-9-1-4 and BT-549, while expression in non-tumorigenic cell line MCF-12A was either basal or slightly downregulated. We further examined the expression of the CPT gene in breast cancer (11-9-1-4, BT-549) and non-tumorigenic cell lines (MCF-12A, MCF-12F). We found that the CPT gene is overexpressed in breast cancer cell lines compared to the non-tumorigenic cell lines. Furthermore, the activity of CPT in forming PC is increased in the breast cancer cell lines cultured for 24 h. Additionally, we examined the CPT activity in the presence of nanomolar concentrations of Ro5-4864. Biosynthesis of PC was increased in breast cancer cell lines upon treatment. We therefore propose that Ro5-4864 facilitates PC formation, a process important in membrane biogenesis for proliferating cells.

  16. Efficiently Combining Water Reuse and Desalination through Forward Osmosis—Reverse Osmosis (FO-RO) Hybrids: A Critical Review

    PubMed Central

    Blandin, Gaetan; Verliefde, Arne R.D.; Comas, Joaquim; Rodriguez-Roda, Ignasi; Le-Clech, Pierre

    2016-01-01

    Forward osmosis (FO) is a promising membrane technology to combine seawater desalination and water reuse. More specifically, in a FO-reverse osmosis (RO) hybrid process, high quality water recovered from the wastewater stream is used to dilute seawater before RO treatment. As such, lower desalination energy needs and/or water augmentation can be obtained while delivering safe water for direct potable reuse thanks to the double dense membrane barrier protection. Typically, FO-RO hybrid can be a credible alternative to new desalination facilities or to implementation of stand-alone water reuse schemes. However, apart from the societal (public perception of water reuse for potable application) and water management challenges (proximity of wastewater and desalination plants), FO-RO hybrid has to overcome technical limitation such as low FO permeation flux to become economically attractive. Recent developments (i.e., improved FO membranes, use of pressure assisted osmosis, PAO) demonstrated significant improvement in water flux. However, flux improvement is associated with drawbacks, such as increased fouling behaviour, lower rejection of trace organic compounds (TrOCs) in PAO operation, and limitation in FO membrane mechanical resistance, which need to be better considered. To support successful implementation of FO-RO hybrid in the industry, further work is required regarding up-scaling to apprehend full-scale challenges in term of mass transfer limitation, pressure drop, fouling and cleaning strategies on a module scale. In addition, refined economics assessment is expected to integrate fouling and other maintenance costs/savings of the FO/PAO-RO hybrid systems, as well as cost savings from any treatment step avoided in the water recycling. PMID:27376337

  17. Efficiently Combining Water Reuse and Desalination through Forward Osmosis-Reverse Osmosis (FO-RO) Hybrids: A Critical Review.

    PubMed

    Blandin, Gaetan; Verliefde, Arne R D; Comas, Joaquim; Rodriguez-Roda, Ignasi; Le-Clech, Pierre

    2016-07-01

    Forward osmosis (FO) is a promising membrane technology to combine seawater desalination and water reuse. More specifically, in a FO-reverse osmosis (RO) hybrid process, high quality water recovered from the wastewater stream is used to dilute seawater before RO treatment. As such, lower desalination energy needs and/or water augmentation can be obtained while delivering safe water for direct potable reuse thanks to the double dense membrane barrier protection. Typically, FO-RO hybrid can be a credible alternative to new desalination facilities or to implementation of stand-alone water reuse schemes. However, apart from the societal (public perception of water reuse for potable application) and water management challenges (proximity of wastewater and desalination plants), FO-RO hybrid has to overcome technical limitation such as low FO permeation flux to become economically attractive. Recent developments (i.e., improved FO membranes, use of pressure assisted osmosis, PAO) demonstrated significant improvement in water flux. However, flux improvement is associated with drawbacks, such as increased fouling behaviour, lower rejection of trace organic compounds (TrOCs) in PAO operation, and limitation in FO membrane mechanical resistance, which need to be better considered. To support successful implementation of FO-RO hybrid in the industry, further work is required regarding up-scaling to apprehend full-scale challenges in term of mass transfer limitation, pressure drop, fouling and cleaning strategies on a module scale. In addition, refined economics assessment is expected to integrate fouling and other maintenance costs/savings of the FO/PAO-RO hybrid systems, as well as cost savings from any treatment step avoided in the water recycling.

  18. Lichen scléro-atrophique extra-génital: à propos d’un cas

    PubMed Central

    Zemmez, Youssef; Amraoui, Mohammed El; Bouhamidi, Ahmed; Azhari, Jaouad El; Ismaili, Nadia; Benzekri, Laila; Meziane, Mariame; Hassam, Badreddine; Senouci, Karima

    2016-01-01

    Le lichen scléro-atrophique est une dermatose inflammatoire d'évolution chronique, avec un tropisme particulier pour les muqueuses génitales externes, l'atteinte cutanée isolée reste rare. Nous rapportons un cas de lichen scléro-atrophique chez une femme avec atteinte purement cutanée soulignant ainsi l'intérêt d'évoquer ce diagnostic en absence d'une atteinte génitale évidente. PMID:28292152

  19. Transiting exoplanets from the CoRoT space mission. XXI. CoRoT-19b: a low density planet orbiting an old inactive F9V-star

    NASA Astrophysics Data System (ADS)

    Guenther, E. W.; Díaz, R. F.; Gazzano, J.-C.; Mazeh, T.; Rouan, D.; Gibson, N.; Csizmadia, Sz.; Aigrain, S.; Alonso, R.; Almenara, J. M.; Auvergne, M.; Baglin, A.; Barge, P.; Bonomo, A. S.; Bordé, P.; Bouchy, F.; Bruntt, H.; Cabrera, J.; Carone, L.; Carpano, S.; Cavarroc, C.; Deeg, H. J.; Deleuil, M.; Dreizler, S.; Dvorak, R.; Erikson, A.; Ferraz-Mello, S.; Fridlund, M.; Gandolfi, D.; Gillon, M.; Guillot, T.; Hatzes, A.; Havel, M.; Hébrard, G.; Jehin, E.; Jorda, L.; Lammer, H.; Léger, A.; Moutou, C.; Nortmann, L.; Ollivier, M.; Ofir, A.; Pasternacki, Th.; Pätzold, M.; Parviainen, H.; Queloz, D.; Rauer, H.; Samuel, B.; Santerne, A.; Schneider, J.; Tal-Or, L.; Tingley, B.; Weingrill, J.; Wuchterl, G.

    2012-01-01

    Context. Observations of transiting extrasolar planets are of key importance to our understanding of planets because their mass, radius, and mass density can be determined. These measurements indicate that planets of similar mass can have very different radii. For low-density planets, it is generally assumed that they are inflated owing to their proximity to the host-star. To determine the causes of this inflation, it is necessary to obtain a statistically significant sample of planets with precisely measured masses and radii. Aims: The CoRoT space mission allows us to achieve a very high photometric accuracy. By combining CoRoT data with high-precision radial velocity measurements, we derive precise planetary radii and masses. We report the discovery of CoRoT-19b, a gas-giant planet transiting an old, inactive F9V-type star with a period of four days. Methods: After excluding alternative physical configurations mimicking a planetary transit signal, we determine the radius and mass of the planet by combining CoRoT photometry with high-resolution spectroscopy obtained with the echelle spectrographs SOPHIE, HARPS, FIES, and SANDIFORD. To improve the precision of its ephemeris and the epoch, we observed additional transits with the TRAPPIST and Euler telescopes. Using HARPS spectra obtained during the transit, we then determine the projected angle between the spin of the star and the orbit of the planet. Results: We find that the host star of CoRoT-19b is an inactive F9V-type star close to the end of its main-sequence life. The host star has a mass M∗ = 1.21 ± 0.05 M⊙ and radius R∗ = 1.65 ± 0.04 R⊙. The planet has a mass of MP = 1.11 ± 0.06 MJup and radius of RP = 1.29 ± 0.03 RJup. The resulting bulk density is only ρ = 0.71 ± 0.06 g cm-3, which is much lower than that for Jupiter. Conclusions: The exoplanet CoRoT-19b is an example of a giant planet of almost the same mass as Jupiter but a ≈30% larger radius. The CoRoT space mission, launched on

  20. Inhibitors of Pyruvate Carboxylase

    PubMed Central

    Zeczycki, Tonya N.; Maurice, Martin St.; Attwood, Paul V.

    2010-01-01

    This review aims to discuss the varied types of inhibitors of biotin-dependent carboxylases, with an emphasis on the inhibitors of pyruvate carboxylase. Some of these inhibitors are physiologically relevant, in that they provide ways of regulating the cellular activities of the enzymes e.g. aspartate and prohibitin inhibition of pyruvate carboxylase. Most of the inhibitors that will be discussed have been used to probe various aspects of the structure and function of these enzymes. They target particular parts of the structure e.g. avidin – biotin, FTP – ATP binding site, oxamate – pyruvate binding site, phosphonoacetate – binding site of the putative carboxyphosphate intermediate. PMID:22180764

  1. Acquired Factor V Inhibitor

    PubMed Central

    Hirai, Daisuke; Yamashita, Yugo; Masunaga, Nobutoyo; Katsura, Toshiaki; Akao, Masaharu; Okuno, Yoshiaki; Koyama, Hiroshi

    2016-01-01

    Inhibitors directed against factor V rarely occur, and the clinical symptoms vary. We herein report the case of a patient who presented with a decreased factor V activity that had decreased to <3 %. We administered vitamin K and 6 units of fresh frozen plasma, but she thereafter developed an intracerebral hemorrhage. It is unclear whether surgery >10 years earlier might have caused the development of a factor V inhibitor. The treatment of acquired factor V inhibitors is mainly the transfusion of platelet concentrates and corticosteroids. Both early detection and the early initiation of the treatment of factor V inhibitor are thus considered to be important. PMID:27746446

  2. Revisiting the SAR of the Antischistosomal Aryl Hydantoin (Ro 13-3978)

    PubMed Central

    2016-01-01

    The aryl hydantoin 1 (Ro 13-3978) was identified in the early 1980s as a promising antischistosomal lead compound. However, this series of aryl hydantoins produced antiandrogenic side effects in the host, a not unexpected outcome given their close structural similarity to the antiandrogenic drug nilutamide. Building on the known SAR of this compound series, we now describe a number of analogs of 1 designed to maximize structural diversity guided by incorporation of substructures and functional groups known to diminish ligand–androgen receptor interactions. These analogs had calculated polar surface area (PSA), measured LogD7.4, aqueous kinetic solubility, and estimated plasma protein binding values in ranges predictive of good ADME profiles. The principal SAR insight was that the hydantoin core of 1 is required for high antischistosomal activity. We identified several compounds with high antischistosomal efficacy that were less antiandrogenic than 1. These data provide direction for the ongoing optimization of antischistosomal hydantoins. PMID:27933964

  3. High-efficiency optical coupling single-sideband modulation for OFDM-RoF-PON systems

    NASA Astrophysics Data System (ADS)

    Xue, Xuwei; Ji, Wei; Kang, Zhaoyuan; Huang, Kangrui; Li, Xiao

    2015-12-01

    We report on an OFDM-RoF-PON system based on novel optical coupling single-sideband (O-SSB) modulation for one wavelength carrying one baseband and two radio frequency (RF) signals. The impact of nonlinear distortion consisting of harmonic distortion (HD) and intermodulation distortion (IMD) in this system is theoretically investigated. Transmission over 0 km and 40 km of standard single mode fiber is successfully demonstrated and it is indicated that modulation index 0.6 is more adapted to O-SSB modulation. The error vector magnitude (EVM) of system based on O-SSB modulation after transmission over 40 km is <0.1. For O-SSB modulation, bit error rate (BER) after 40 km transmission is below forward error correction (FEC) limit of 10-3.

  4. Pharmacokinetics of Ro 03-8799 in mice bearing melanosarcoma: comparison with tumors without melanin

    SciTech Connect

    Laurent, F.; Canal, P.; Soula, G.

    1989-04-01

    The pharmacokinetics of Ro 03-8799 has been studied in melanic and non-melanic tumor bearing mice after iv administration of 150 mg/kg. The peak concentration in B16 melanosarcoma tumor reached 152 micrograms/g, that is 7.6-fold higher than the plasma concentration at the same time. This concentration is 3-times greater than that obtained in the tumor of mice bearing non-melanic sarcoma (DB16) or Lewis lung carcinoma (3LL). The exposure of B16 tumor (AUC) is respectively 15-times and 11-times higher than the 3LL and the DB16 ones. These experimental data confirm that this 2-nitro-imidazol compound has an important affinity for melanin and suggest that it might be used as a radiosensitizer for the treatment of malignant melanoma.

  5. Looking for planetary candidates in the CoRoT Long Run LRc10

    NASA Astrophysics Data System (ADS)

    Zannoni, A.; Borsa, F.; Poretti, E.; Lodato, G.; Rainer, M.; Frustagli, G.

    We analysed the public data of the CoRoT Long Run LRc10 looking for planetary candidates. In a first step we removed outliers and trends caused by stellar activity and instrumental problems. Then we applied the Box-fitting Least Squares (BLS) algorithm to detect periodic decreases in luminosity. From all the significative transit detections, we selected the ones that passed different checks. For the 7 planetary candidates found, we applied a new ``ad hoc'' normalization and fitted the orbital parameters, to verify their reliability. Using the stellar temperature information, we could estimate the dimensions that the candidates should have if confirmed. Our research method demonstrated to be sensitive to candidates with hypothetic dimension up to ˜3.5 REarth on stars of mag V≃14.

  6. Variational Calculations of Ro-Vibrational Energy Levels and Transition Intensities for Tetratomic Molecules

    NASA Technical Reports Server (NTRS)

    Schwenke, David W.; Langhoff, Stephen R. (Technical Monitor)

    1995-01-01

    A description is given of an algorithm for computing ro-vibrational energy levels for tetratomic molecules. The expressions required for evaluating transition intensities are also given. The variational principle is used to determine the energy levels and the kinetic energy operator is simple and evaluated exactly. The computational procedure is split up into the determination of one dimensional radial basis functions, the computation of a contracted rotational-bending basis, followed by a final variational step coupling all degrees of freedom. An angular basis is proposed whereby the rotational-bending contraction takes place in three steps. Angular matrix elements of the potential are evaluated by expansion in terms of a suitable basis and the angular integrals are given in a factorized form which simplifies their evaluation. The basis functions in the final variational step have the full permutation symmetries of the identical particles. Sample results are given for HCCH and BH3.

  7. Ro-vibrational averaging of the isotropic hyperfine coupling constant for the methyl radical

    SciTech Connect

    Adam, Ahmad Y.; Jensen, Per; Yachmenev, Andrey; Yurchenko, Sergei N.

    2015-12-28

    We present the first variational calculation of the isotropic hyperfine coupling constant of the carbon-13 atom in the CH{sub 3} radical for temperatures T = 0, 96, and 300 K. It is based on a newly calculated high level ab initio potential energy surface and hyperfine coupling constant surface of CH{sub 3} in the ground electronic state. The ro-vibrational energy levels, expectation values for the coupling constant, and its temperature dependence were calculated variationally by using the methods implemented in the computer program TROVE. Vibrational energies and vibrational and temperature effects for coupling constant are found to be in very good agreement with the available experimental data. We found, in agreement with previous studies, that the vibrational effects constitute about 44% of the constant’s equilibrium value, originating mainly from the large amplitude out-of-plane bending motion and that the temperature effects play a minor role.

  8. A hybrid ED/RO process for TDS reduction of produced waters

    SciTech Connect

    Tsai, S.P.; Datta, R.; Frank, J.R.

    1995-12-31

    Large volumes of produced waters are generated from natural gas production. In the United States the prevailing management practice for produced waters is deep well injection, but this practice is costly. Therefore minimizing the need for deep well injection is desirable. A major treatment issue for produced waters is the reduction of total dissolved solids (TDS), which consist mostly of inorganic salts. A hybrid electrodialysis/reverse-osmosis (ED/RO) treatment process is being developed to concentrate the salts in produced waters and thereby reduce the volume of brine that needs to be managed for disposal. The desalted water can be used beneficially or discharged. In this study, laboratory feasibility experiments were conducted by using produced waters from multiple sites. A novel-membrane configuration approach to prevent fouling and scale formation was developed and demonstrated. Results of laboratory experiments and plans for field demonstration are discussed.

  9. Constructing generalized Cesàro formulas for finite plane strains

    NASA Astrophysics Data System (ADS)

    Georgievskii, D. V.

    2014-05-01

    The problem of finding the displacement vector from a system of nonlinear differential equations which includes displacement gradient components is studied. Expressions on the right side of this system for certain parameter values have the kinematic sense of Lagrange and Euler finite strain tensors. The task is to construct generalized Cesàro formulas for finite strains. The construction of the solution consists of two stages (algebraic and differential), and the second is performed for space whose dimension is greater than or equal to two. An algorithm for the inversion of the original system is proposed, and analytical constructions for the case of two-dimensional space are performed. The problem is solved at the first (algebraic) stage, i.e., an exact analytical expression for the displacement vector components is derived through the known finite strain tensor and an unknown scalar function having the kinematic sense of rotation. Necessary conditions for the existence of this relationship are formulated.

  10. Doppler mapping of four roAp stars with anomalous lithium abundance

    NASA Astrophysics Data System (ADS)

    Polosukhina, N.; Shulyak, D.; Shavrina, A.; Lyashko, D.; Drake, N.; Glagolevsky, Y.; Kudryavtsev, D.; Smirnova, M.

    2014-11-01

    We present the first results from Doppler Imaging of two roAp stars, HD 12098 and HD 60435, that show strong and variable Li lines in their spectra. High-resolution spectra were obtained with the Russian 6-m BTA telescope, and with the HARPS and VLT/UVES instruments at ESO. We derived the surface abundance distribution of Li and Pr and analysed the correlation between the positions of the Li-abundance spots and magnetic field. We compare our results with Doppler Imaging mapping previously obtained for two CP2 stars, HD 83668 and HD 3980, and discuss the common properties of the locations of the ``Li spots'' on the surfaces of magnetic chemically peculiar A-type stars.

  11. The CoRoT and Kepler Revolution in Stellar Variability Studies

    NASA Astrophysics Data System (ADS)

    Degroote, Pieter; Debosscher, Jonas

    2012-04-01

    Space-based observations of variable stars have revolutionized the field of variability studies. Dedicated satellites such as the CoRoT and Kepler missions have duty cycles which are unachievable from the ground, and effectively solve many of the aliasing problems prevalent in ground-based observation campaigns. Moreover, the location above the Earth's atmosphere eliminates a major source of scatter prevalent in observations from the ground. These two major improvements in instrumentation have triggered significant increases in our knowledge of the stars, but in order to reap the full benefits they are also obliging the community to adopt more efficient techniques for handling, analysing and interpreting the vast amounts of new, high-precision data in an effective yet comprehensive manner. This workshop heard an outline of the history and development of asteroseismology, and descriptions of the two space missions (CoRoT and Kepler) which have been foremost in accelerating those recent developments. Informal discussions on numerous points peppered the proceedings, and involved the whole audience at times. The conclusions which the workshop reached have been distilled into a list of seven recommendations (Section 5) for the asteroseismology community to study and absorb. In fact, while addressing activities (such as stellar classification or analysing and modelling light curves) that could be regarded as specific to the community in question, the recommendations include advice on matters such as improving communication, incorporating trans-disciplinary knowledge and involving the non-scientific public that are broad enough to serve as guidelines for the astrophysical community at large.

  12. The CoRoT satellite in flight: description and performance

    NASA Astrophysics Data System (ADS)

    Auvergne, M.; Bodin, P.; Boisnard, L.; Buey, J.-T.; Chaintreuil, S.; Epstein, G.; Jouret, M.; Lam-Trong, T.; Levacher, P.; Magnan, A.; Perez, R.; Plasson, P.; Plesseria, J.; Peter, G.; Steller, M.; Tiphène, D.; Baglin, A.; Agogué, P.; Appourchaux, T.; Barbet, D.; Beaufort, T.; Bellenger, R.; Berlin, R.; Bernardi, P.; Blouin, D.; Boumier, P.; Bonneau, F.; Briet, R.; Butler, B.; Cautain, R.; Chiavassa, F.; Costes, V.; Cuvilho, J.; Cunha-Parro, V.; de Oliveira Fialho, F.; Decaudin, M.; Defise, J.-M.; Djalal, S.; Docclo, A.; Drummond, R.; Dupuis, O.; Exil, G.; Fauré, C.; Gaboriaud, A.; Gamet, P.; Gavalda, P.; Grolleau, E.; Gueguen, L.; Guivarc'h, V.; Guterman, P.; Hasiba, J.; Huntzinger, G.; Hustaix, H.; Imbert, C.; Jeanville, G.; Johlander, B.; Jorda, L.; Journoud, P.; Karioty, F.; Kerjean, L.; Lafond, L.; Lapeyrere, V.; Landiech, P.; Larqué, T.; Laudet, P.; Le Merrer, J.; Leporati, L.; Leruyet, B.; Levieuge, B.; Llebaria, A.; Martin, L.; Mazy, E.; Mesnager, J.-M.; Michel, J.-P.; Moalic, J.-P.; Monjoin, W.; Naudet, D.; Neukirchner, S.; Nguyen-Kim, K.; Ollivier, M.; Orcesi, J.-L.; Ottacher, H.; Oulali, A.; Parisot, J.; Perruchot, S.; Piacentino, A.; Pinheiro da Silva, L.; Platzer, J.; Pontet, B.; Pradines, A.; Quentin, C.; Rohbeck, U.; Rolland, G.; Rollenhagen, F.; Romagnan, R.; Russ, N.; Samadi, R.; Schmidt, R.; Schwartz, N.; Sebbag, I.; Smit, H.; Sunter, W.; Tello, M.; Toulouse, P.; Ulmer, B.; Vandermarcq, O.; Vergnault, E.; Wallner, R.; Waultier, G.; Zanatta, P.

    2009-10-01

    Context: CoRoT is a space telescope dedicated to stellar seismology and the search for extrasolar planets. The mission is led by the CNES in association with French laboratories and has a large international participation. The European Space Agency (ESA), Austria, Belgium, and Germany contribute to the payload, and Spain and Brazil contribute to the ground segment. Development of the spacecraft, which is based on a PROTEUS low earth orbit (LEO) recurrent platform, commenced in October 2000, and the satellite was launched on December 27, 2006. Aims: The instrument and platform characteristics prior to launch have been described in ESA publication (SP-1306). In the present paper we explain the behaviour in flight, based on raw and corrected data. Methods: Five runs have been completed since January 2007. The data used here are essentially those acquired during the commissioning phase and from a long run that lasted 146 days. These enable us to give a complete overview of the instrument and platform behaviour for all environmental conditions. The ground based data processing is not described in detail because the most important method has been published elsewhere. Results: We show that the performance specifications are easily satisfied when the environmental conditions are favourable. Most of the perturbations, hence data corrections, are related to LEO perturbations: high energy particles inside the South Atlantic Anomaly (SAA), eclipses and temperature variations, and line of sight fluctuations due to the attitude control system. Straylight due to the reflected light from the earth, which is controlled by the telescope and baffle design, appears to be negligible. The CoRoT space mission, launched on December 27th 2006, has been developed and is operated by CNES, with contributions from Austria, Belgium, Brazil, ESA, Germany and Spain. Four French laboratories associated with the CNRS (LESIA, LAM, IAS, OMP) collaborate with CNES on the satellite development. The

  13. RoHS regulated substances in mixed plastics from waste electrical and electronic equipment.

    PubMed

    Wäger, Patrick A; Schluep, Mathias; Müller, Esther; Gloor, Rolf

    2012-01-17

    The disposal and recovery of plastics from waste electrical and electronic equipment (WEEE) are of considerable importance, both from an environmental and an economic perspective. This paper presents the results of a study investigating current concentrations of hazardous substances in mixed plastics from WEEE and their implications for an environmentally sound recovery. The study included 53 sampling campaigns for mixed plastics from WEEE. The samples were analyzed with regard to heavy metals (cadmium, chromium, mercury, and lead) and flame retardants (PentaBDE, OctaBDE, DecaBDE, DecaBB) regulated in the RoHS Directive. Besides these substances, other brominated flame retardants known to occur in electronics (HBCD, TBBPA) as well as the total bromine and phosphorus contents were considered. Results show that no mixed plastics fraction from WEEE is completely free from substances regulated in the RoHS Directive. The lowest number and average concentrations were found in flat screen monitors. The highest concentrations were found in mixed plastics from CRT monitors and TVs. Mixed plastics fractions with high average concentrations of heavy metals originate from the treatment of small household appliances (cadmium), ICT equipment (lead), and consumer equipment (lead). Mixed plastics fractions with high average concentrations of brominated flame retardants mainly originate from the treatment of small household appliances for high temperature applications (DecaBDE), CRT monitors (OctaBDE and DecaBDE) and consumer equipment (DecaBDE), in particular CRT TVs (DecaBDE). To avoid a dissipation of hazardous substances into plastics and the environment, it is recommended that mixed plastics from WEEE are subject to a strict quality management.

  14. Presenting new exoplanet candidates for the CoRoT chromatic light curves

    NASA Astrophysics Data System (ADS)

    Boufleur, Rodrigo; Emilio, Marcelo; Andrade, Laerte; Janot-Pacheco, Eduardo; De La Reza, Ramiro

    2015-08-01

    One of the most promising topics of modern Astronomy is the discovery and characterization of extrasolar planets due to its importance for the comprehension of planetary formation and evolution. Missions like MOST (Microvariability and Oscillations of Stars Telescope) (Walker et al., 2003) and especially the satellites dedicated to the search for exoplanets CoRoT (Convection, Rotation and planetary Transits) (Baglin et al., 1998) and Kepler (Borucki et al., 2003) produced a great amount of data and together account for hundreds of new discoveries. An important source of error in the search for planets with light curves obtained from space observatories are the displacements occuring in the data due to external causes. This artificial charge generation phenomenon associated with the data is mainly caused by the impact of high energy particles onto the CCD (Pinheiro da Silva et al. 2008), although other sources of error, not as well known also need to be taken into account. So, an effective analysis of the light curves depends a lot on the mechanisms employed to deal with these phenomena. To perform our research, we developed and applied a different method to fix the light curves, the CDAM (Corot Detrend Algorithm Modified), inspired by the work of Mislis et al. (2012). The paradigms were obtained using the BLS method (Kovács et al., 2002). After a semiautomatic pre-analysis associated with a visual inspection of the planetary transits signatures, we obtained dozens of exoplanet candidates in very good agreement with the literature and also new unpublished cases. We present the study results and characterization of the new cases for the chromatic channel public light curves of the CoRoT satellite.

  15. A 60GHz RoF(radio-over-fiber) transmission system based on PM modulator

    NASA Astrophysics Data System (ADS)

    Wang, Xin; Liu, Yi; Wang, Wen-Ting

    2016-11-01

    As one of the most important applications of microwave photonic ROF (Radio over Fiber) system which combines the advantages of optical communication and wireless communication is a good candidate for broadband mobile Communication In this paper, we built and simulation a 60GHz RoF(Radio-over-Fiber) transmission system based on PM modulator. First, we introduce the PM-IM(Phase modulation to intensity modulation) modulation mechanisms by the breaking the phase balanced approach. This method solves the problem that the constant envelope (phase modulation signal) generated by the phase modulator can not be directly detected by a photo detector. A standard single-mode fiber (SMF) is connected input to the F-P(Fabry-Perot) optical filter, which is to achieve the PM-IM modulation conversion by changing the wavelength of the laser or the frequency of the modulation factor of the F-P optical filter to adapt to different fiber lengths and the signal transmission rate. These two methods which changing the phase relationship between the optical carrier and the optical side band can realize the ideal phase transition to obtain efficient and low loss modulation conversion. Finally, the simulation results show that different fiber lengths and the signal transmission rate configuration of different wavelength of the laser or the frequency of the modulation factor of the F-P optical filter, the BER performance and the eye diagram of the 60GHz RoF transmission system signals have been improved based on these PM-IM modulation methods.

  16. A self-consistent chemically stratified atmosphere model for the roAp star 10 Aquilae

    NASA Astrophysics Data System (ADS)

    Nesvacil, N.; Shulyak, D.; Ryabchikova, T. A.; Kochukhov, O.; Akberov, A.; Weiss, W.

    2013-04-01

    Context. Chemically peculiar A-type (Ap) stars are a subgroup of the CP2 stars that exhibit anomalous overabundances of numerous elements, e.g. Fe, Cr, Sr, and rare earth elements. The pulsating subgroup of Ap stars, the roAp stars, present ideal laboratories to observe and model pulsational signatures, as well as the interplay of the pulsations with strong magnetic fields and vertical abundance gradients. Aims: Based on high-resolution spectroscopic observations and observed stellar energy distributions, we construct a self-consistent model atmosphere for the roAp star 10 Aquilae (HD 176232). It accounts for modulations of the temperature-pressure structure caused by vertical abundance gradients. We demonstrate that such an analysis can be used to determine precisely the fundamental atmospheric parameters required for pulsation modelling. Methods: Average abundances were derived for 56 species. For Mg, Si, Ca, Cr, Fe, Co, Sr, Pr, and Nd, vertical stratification profiles were empirically derived using the DDAFit minimisation routine together with the magnetic spectrum synthesis codeSynthmag. Model atmospheres were computed with the LLmodels code, which accounts for the individual abundances and stratification of chemical elements. Results: For the final model atmosphere, Teff = 7550 K and log (g) = 3.8 were adopted. While Mg, Si, Co, and Cr exhibit steep abundance gradients, Ca, Fe, and Sr showed much wider abundance gradients between logτ5000 = -1.5 and 0.5. Elements Mg and Co were found to be the least stratified, while Ca and Sr showed strong depth variations in abundance of up to ≈ 6 dex. Table 4 and Figs. 10-12 are available in electronic form at http://www.aanda.org

  17. The CoRoT chemical peculiar target star HD 49310

    NASA Astrophysics Data System (ADS)

    Paunzen, E.; Fröhlich, H.-E.; Netopil, M.; Weiss, W. W.; Lüftinger, T.

    2015-02-01

    Context. The magnetic chemically peculiar (CP) stars of the upper main sequence are well-suited laboratories for investigating the influence of local magnetic fields on the stellar surface because they produce inhomogeneities (spots) that can be investigated in detail as the star rotates. Aims: We studied the inhomogeneous surface structure of the CP2 star HD 49310 based on high-quality CoRoT photometry obtained during 25 days. The data have nearly no gaps. This analysis is similar to a spectroscopic Doppler-imaging analysis, but it is not a tomographic method. Methods: We performed detailed light-curve fitting in terms of stationary circular bright spots. Furthermore, we derived astrophysical parameters with which we located HD 49310 within the Hertzsprung-Russell diagram. We also investigated the possible connection of this star to the nearby young open cluster NGC 2264. Results: With a Bayesian technique, we produced a surface map that shows six bright spots. After removing some artefacts, the residuals of the observed and synthetic photometric data are ± 0.123 mmag. The rotational period of the star is P = 1.91909 ± 0.00001 days. Our photometric observations therefore cover about 13 full rotational cycles. Three spots are very large with diameters of ≃ 40deg. The spots are brighter by 40% than the unperturbed stellar photosphere. Conclusions: HD 49310 is a classical silicon (CP2) star with a mass of about 3 M⊙. It is not a member of NGC 2264. Our analysis shows the potential of using high-quality photometric data to analyse the surface structure of CP stars. A comprehensive analysis of similar archival data, preferrably from space missions, would contribute significantly to our understanding of surface phenomena of CP stars and their temporal evolution. The CoRoT space mission was developed and is operated by the French space agency CNES, with participation of ESA's RSSD and Science Programmes, Austria, Belgium, Brazil, Germany, and Spain.

  18. Effects of a D2 receptor agonist RO 41-9067 alone and with clonidine on sleep parameters in the rat.

    PubMed

    Python, A; de Saint Hilaire, Z; Gaillard, J M

    1996-02-01

    The effects of RO 41-9067, a D2 dopamine receptors agonist, on different sleep parameters were studied in the rat. RO 41-9067 dose dependently decreased paradoxical sleep, and only at the higher dose increased waking during the light period. In contrast, the higher dose of RO 41-9067 increased paradoxical sleep and decreased waking during the dark period. Finally, the combination of RO 41-9067 and clonidine significantly prevent the decrease of total sleep time and paradoxical sleep found after clonidine alone. These results, compared with those of classical D2 dopamine receptors agonists, suggest an action for RO 41-9067 on D2 dopamine receptors depending on the cerebral structure, a different action particularly on the striatum and/or on the structures responsible for paradoxical sleep. An active role for D2 dopamine receptors and an interaction between noradrenergic and dopaminergic systems in the regulation of sleep is proposed.

  19. Temporal Spectral Analysis of Be stars observed with CoRoT satellite

    NASA Astrophysics Data System (ADS)

    Emilio, Marcelo; Janot Pacheco, Eduardo; Andrade, Laerte

    . Nevertheless, to measure frequencies with great accuracy in stars requires both high photometric precision and high time-frequency resolution. The CoRoT (Convection, Rotation and planetary Transits) satellite opens for the first time in history the possibility of fulfilling this goal. CoRoT is an experiment of astronomy dedicated to seismology and the detection of extrasolar planet transits. It was launched on December 2006 in an inertial polar orbit at an altitude of 897 mathrm{km}. The instrument is fed by a phi=27 textrm{cm} telescope. Its scientific program is three-fold consisting of: (1) The seismology core program (SISMO), which concerns the seismic study of ˜10 bright (6RoT ID 102761769 observed by CoRoT satellite. We found two close frequencies related to the .CoRoT ID 102761769 star. They are 2.465 c d(-1) (28.5 mathrm{mu Hz}) and 2.441 c d(-1) (28.2 mathrm{mu Hz}). The precision to which those frequencies were found is 0.018 c d(-1) (0.2 mathrm{mu Hz}). The projected stellar rotation was estimated to be 120 km s(-1) from the Fourier transform of spectral lines. If CoRoT-ID 102761769 is a typical Galactic Be star it rotates near the critical velocity. The critical rotation frequency of a typical B5-6 star is about 3.5 c d(-1) (40.5 mathrm{mu Hz}), which implies that the above frequencies are really caused by stellar pulsations rather than star's rotation. HD 171219 frequencies 1.113, 1.130, 1.146 c * d(-1) form a triplet with the

  20. 77 FR 1707 - National Toxicology Program (NTP) Final Process for Preparation of the Report on Carcinogens (RoC)

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-01-11

    ... available on the NTP Web site ( http://ntp.niehs.nih.gov/go/rocprocess ) or by contacting Dr. Ruth Lunn (see...) on December 15, 2011 ( http://ntp.niehs.nih.gov/go/9741 ). The NTP now announces the final process....gov/go/rocprocess ) or by contacting Dr. Lunn (see ADDRESSES). Background Information on the RoC...

  1. Behaviour of RO98pHt polyamide membrane in reverse osmosis and low reverse osmosis conditions for phenol removal.

    PubMed

    Hidalgo, A M; León, G; Gómez, M; Murcia, M D; Gómez, E; Gómez, J L

    2011-10-01

    Phenolic compounds and their derivatives are very common pollutants in wastewaters. Among the methods described for their removal, pressure-driven membrane processes are considered as a reliable alternative. Our research group has previously studied phenol removal in reverse osmosis (RO) conditions and obtained very low rejection percentages. Subsequently, when low reverse osmosis (LRO) conditions were studied, the organic rejection percentages improved. To further our knowledge in this respect, the main objective of this work was to study the behaviour of the polyamide thin-film composite membrane RO98pHt used for phenol removal in RO and LRO conditions. The influence of different operating pressures, phenol feed concentrations and pH on permeate flux and phenol rejection was studied. Low reverse osmosis conditions led to higher phenol rejection percentages in all the assayed conditions, suggesting that other factors related to the molecular characteristics of the organic molecules, such as solubility, acidity and hydrogen bonding capacity, play an important role in the rejection percentage attained. As expected, permeate flux was greater in RO conditions.

  2. The CoRoT-GES Collaboration: Improving red giants spectroscopic surface gravitity and abundances with asteroseismology

    NASA Astrophysics Data System (ADS)

    Valentini, M.; Chiappini, C.; Miglio, A.; Montalbán, J.; Rodrigues, T.; Mosser, B.; Anders, F.; the CoRoT RG Group; GES Consortium, the

    2016-09-01

    Nowadays large spectroscopic surveys, like the Gaia-ESO Survey (GES), provide unique stellar databases for better investigating the formation and evolution of our Galaxy. Great attention must be paid to the accuracy of the basic stellar properties derived: large uncertainties in stellar parameters lead to large uncertainties in abundances, distances and ages. Asteroseismology has a key role in this context: when seismic information is combined with information derived from spectroscopic analysis, highly precise constraints on distances, masses, extinction and ages of red giants can be obtained. In the light of this promising joint action, we started the CoRoT-GES collaboration. We present a set of 1111 CoRoT stars, observed by GES from December 2011 to July 2014, these stars belong to the CoRoT field LRc01, pointing at the inner Galactic disk. Among these stars, 534 have reliable global seismic parameters. By combining seismic informations and spectroscopy, we derived precise stellar parameters, ages, kinematic and orbital parameters and detailed element abundances for this sample of stars. We also show that, thanks to asteroseismology, we are able to obtain a higher precision than what can be achieved by the standard spectroscopic means. This sample of CoRoT red giants, spanning Galactocentric distances from 5 to 8 kpc and a wide age interval (1-13 Gyr), provides us a representative sample for the inner disk population.

  3. Measuring E(GSH) and H2O2 with roGFP2-based redox probes.

    PubMed

    Morgan, Bruce; Sobotta, Mirko C; Dick, Tobias P

    2011-12-01

    Redox biochemistry plays an important role in a wide range of cellular events. However, investigation of cellular redox processes is complicated by the large number of cellular redox couples, which are often not in equilibrium with one another and can vary significantly between subcellular compartments and cell types. Further, it is becoming increasingly clear that different redox systems convey different biological information; thus it makes little sense to talk of an overall "cellular redox state". To gain a more differentiated understanding of cellular redox biology, quantitative, redox couple-specific, in vivo measurements are necessary. Unfortunately our ability to investigate specific redox couples or redox-reactive molecules with the necessary degree of spatiotemporal resolution is very limited. The development of genetically encoded redox biosensors offers a promising new way to investigate redox biology. Recently developed redox-sensitive green fluorescent proteins (roGFPs), genetically fused to redox-active proteins, allow rapid equilibration of the roGFP moiety with a specific redox couple. Two probes based on this principle are now available: Grx1-roGFP2 for the measurement of glutathione redox potential (E(GSH)) and roGFP2-Orp1 for measuring changes in H(2)O(2) concentration. Here we provide a detailed protocol for the use of these probes in both yeast and mammalian systems using either plate-reader- or microscopy-based measurements.

  4. Downregulation of (3H)Ro5-4864 binding sites after exposure to peripheral-type benzodiazepines in vitro

    SciTech Connect

    Johnson, M.D.; Wang, J.K.; Morgan, J.I.; Spector, S.

    1986-09-01

    Peripheral-type benzodiazepine (BZD) binding sites undergo a rapid and pronounced downregulation after exposure to these compounds in vitro. Friend erythroleukemia cells were incubated with micromolar concentrations of BZD after which they were washed thoroughly and the binding of the specific peripheral-type BZD radioligand (/sup 3/H)Ro5-4864 was determined. Exposure to the peripheral-type BZD Ro7-3351 decreased the number of (/sup 3/H)Ro5-4864 binding sites from 324 to 41 fmol/10(6) cells with no change in affinity. Downregulation appears to require active cellular processes because it is blocked when exposure to BZD is at 4/sup 0/C rather than at 37/sup 0/C. Furthermore, whereas (/sup 3/H)Ro5-4864 binding is decreased substantially in membrane preparations made from downregulated cells, it is not altered when membrane preparations from control cells are exposed to BZD. The time course of downregulation is quite rapid, as it occurs within minutes. In contrast, the return of sites requires days and there is a close relationship between return of sites and growth of new cells. The ability of BZDs to downregulate correlates more closely with affinity for the peripheral-type site than with biological activity. The ability to undergo downregulation is characteristic of receptors and its occurrence suggests that peripheral-type BZD binding sites are functional receptors.

  5. Finest light curve details, physical parameters, and period fluctuations of CoRoT RR Lyrae stars

    NASA Astrophysics Data System (ADS)

    Benkő, J. M.; Szabó, R.; Derekas, A.; Sódor, Á.

    2016-12-01

    The CoRoT satellite supplied the scientific community with a huge data base of variable stars. Among them the RR Lyrae stars have intensively been discussed in numerous papers in the last few years, but the latest runs have not been checked to find RR Lyrae stars up to now. Our main goal was to fill this gap and complete the CoRoT RR Lyrae sample. We found nine unstudied RR Lyrae stars. Seven of them are new discoveries. We identified three new Blazhko stars. The Blazhko effect shows non-strictly repetitive nature for all stars. The frequency spectrum of the Blazhko star CoRoT 104948132 contains second overtone frequency with the highest known period ratio. The harmonic amplitude and phase declines with the harmonic order were studied for non-Blazhko stars. We found a period dependent but similar shape amplitude decline for all stars. We discovered significant random period fluctuation for one of the two oversampled target, CM Ori. After a successful transformation of the CoRoT band parameters to the Johnson V values we estimated the basic physical properties such as mass, luminosity, metallicity. The sample can be divided into two subgroups with respect to the metallicity but otherwise the physical parameters are in the canonical range of RR Lyrae stars.

  6. Beneficial phosphate recovery from reverse osmosis (RO) concentrate of an integrated membrane system using polymeric ligand exchanger (PLE).

    PubMed

    Kumar, Manish; Badruzzaman, Mohammad; Adham, Samer; Oppenheimer, Joan

    2007-05-01

    Phosphorus (P) discharge to surface water is a major environmental problem. Wastewater treatment is targeted towards removal of this nutrient to prevent degradation of surface water. Integrated membrane systems (IMS) are increasingly being considered for wastewater reclamation, and provide excellent removal of P compounds. However, reverse osmosis (RO), which forms an integral part of these IMSs, concentrates most dissolved substances including P-species such as phosphates in the RO waste stream. In this study, removal of phosphate from this stream using polymeric ligand exchange (PLE) resins was investigated. Further, the possibility of phosphate recovery through struvite (MgNH(4)PO(4).6H(2)O) precipitation was tested. Struvite has been promoted as a slow release fertilizer in recent years. This study demonstrates that PLEs can be successfully used to remove phosphate from RO-concentrate, and to recover more than 85% of the adsorbed phosphorus from the exhausted media and precipitated as a beneficial product (struvite). The approach, presented in this study, suggests advantages of providing economic benefit from a waste product (RO) while avoiding phosphorus discharge to the environment.

  7. The expression of RoTat 1.2 variable surface glycoprotein (VSG) in Trypanosoma evansi and T. equiperdum.

    PubMed

    Claes, F; Verloo, D; De Waal, D T; Majiwa, P A O; Baltz, T; Goddeeris, B M; Büscher, P

    2003-10-20

    In order to define whether the variable antigenic type RoTat 1.2 is restricted to Trypansoma evansi and could be used as antigen in serological tests to differentiate T. evansi from Trypansoma equiperdum, the appearance of RoTat 1.2-specific antibodies in rabbits, experimentally infected with T. evansi and T. equiperdum, respectively, was analyzed. Ten strains of T. evansi and 11 strains of T. equiperdum originating from Asia, Europe, Africa and Latin America were tested. Rabbit pre-infection sera and sera of days 7, 14, 25, 35 post-infection (p.i.) were analyzed for the presence of antibodies reactive with RoTat 1.2 in immune trypanolysis, ELISA/T. evansi and CATT/T. evansi. Within the duration of the infection (maximum 35 days), all T. evansi as well as 9 out of 11 T. equiperdum infected rabbits became positive in all these tests. The rabbits infected with T. equiperdum OVI (South Africa) and BoTat 1.1 (Morocco) remained negative in the immune trypanolysis test although the latter rabbit became positive in the CATT/T. evansi and ELISA/T. evansi. On the contrary, both rabbits were positive in immune trypanolysis when tested against their respective infecting population. From these data, we conclude that most T. equiperdum strains express isoVATs of RoTat 1.2. This explains, in part, why antibody tests based on T. evansi RoTat 1.2 cannot reliably distinguish between infections caused by T. evansi and those caused by T. equiperdum unless it can be proven that most described T. equiperdum are actually misclassified T. evansi.

  8. Water reuse: >90% water yield in MBR/RO through concentrate recycling and CO2 addition as scaling control.

    PubMed

    Joss, Adriano; Baenninger, Claudia; Foa, Paolo; Koepke, Stephan; Krauss, Martin; McArdell, Christa S; Rottermann, Karin; Wei, Yuansong; Zapata, Ana; Siegrist, Hansruedi

    2011-11-15

    Over 1.5 years continuous piloting of a municipal wastewater plant upgraded with a double membrane system (ca. 0.6 m(3) d(-1) of product water produced) have demonstrated the feasibility of achieving high water quality with a water yield of 90% by combining a membrane bioreactor (MBR) with a submerged ultrafiltration membrane followed by a reverse osmosis membrane (RO). The novelty of the proposed treatment scheme consists of the appropriate conditioning of MBR effluent prior to the RO and in recycling the RO concentrates back to the biological unit. All the 15 pharmaceuticals measured in the influent municipal sewage were retained below 100 ng L(-1), a proposed quality parameter, and mostly below detection limits of 10 ng L(-1). The mass balance of the micropollutants shows that these are either degraded or discharged with the excess concentrate, while only minor quantities were found in the excess sludge. The micropollutant load in the concentrate can be significantly reduced by ozonation. A low treated water salinity (<10 mM inorganic salts; 280 ± 70 μS cm(-1)) also confirms that the resulting product has a high water quality. Solids precipitation and inorganic scaling are effectively mitigated by lowering the pH in the RO feed water with CO(2) conditioning, while the concentrate from the RO is recycled to the biological unit where CO(2) is stripped by aeration. This causes precipitation to occur in the bioreactor bulk, where it is much less of a process issue. SiO(2) is the sole exception. Equilibrium modeling of precipitation reactions confirms the effectiveness of this scaling-mitigation approach for CaCO(3) precipitation, calcium phosphate and sulfate minerals.

  9. Low-amplitude variations detected by CoRoT in the B8IIIe star HD 175869

    NASA Astrophysics Data System (ADS)

    Gutiérrez-Soto, J.; Floquet, M.; Samadi, R.; Neiner, C.; Garrido, R.; Fabregat, J.; Frémat, Y.; Diago, P. D.; Huat, A.-L.; Leroy, B.; Emilio, M.; Hubert, A.-M.; Andrade, O. Thizy L.; de Batz, B.; Janot-Pacheco, E.; Espinosa Lara, F.; Martayan, C.; Semaan, T.; Suso, J.; Auvergne, M.; Chaintreuil, S.; Michel, E.; Catala, C.

    2009-10-01

    Context: The origin of the short-term variability in Be stars remains a matter of controversy. Pulsations and rotational modulation are the components of the favored hypothesis. Aims: We present our analysis of CoRoT data of the B8IIIe star HD 175869 observed during the first short run in the center direction (SRC1). Methods: We review both the instrumental effects visible in the CoRoT light curve and the analysis methods used by the CoRoT Be team. We applied these methods to the CoRoT light curve of the star HD 175869. A search for line-profile variations in the spectroscopic data was also performed. We also searched for a magnetic field, by applying the LSD technique to spectropolarimetric data. Results: The light curve exhibits low-amplitude variations of the order of 300 μmag with a double wave shape. A frequency within the range determined for the rotational frequency and 6 of its harmonics are detected. The main frequency and its first harmonic exhibit amplitude variations of a few days. Other significant frequencies of low-amplitude from 25 to a few μmag are also found. The analysis of line profiles from ground-based spectroscopic data does not detect any variation. In addition, no Zeeman signature was found. Conclusions: Inhomogeneities caused by stellar activity in or just above the photosphere are proposed to produce the photometric variability detected by CoRoT in the Be star HD 175869. The hypothesis that non-radial pulsations are the origin of these variations cannot be excluded.

  10. Comparative clustering analysis of variable stars in the Hipparcos, OGLE Large Magellanic Cloud, and CoRoT exoplanet databases

    NASA Astrophysics Data System (ADS)

    Sarro, L. M.; Debosscher, J.; Aerts, C.; López, M.

    2009-10-01

    Context: Discovery of new variability classes in large surveys using multivariate statistics techniques such as clustering, relies heavily on the correct understanding of the distribution of known classes as point processes in parameter space. Aims: Our objective is to analyze the correspondence between the classical stellar variability types and the clusters found in the distribution of light curve parameters and colour indices of stars in the CoRoT exoplanet sample. The final aim is to help in the identification on new types of variability by first identifying the well known variables in the CoRoT sample. Methods: We apply unsupervised classification algorithms to identify clusters of variable stars from modes of the probability density distribution. We use reference variability databases (Hipparcos and OGLE) as a framework to calibrate the clustering methodology. Furthermore, we use the results from supervised classification methods to interpret the resulting clusters. Results: We interpret the clusters in the Hipparcos and OGLE LMC databases in terms of large-amplitude radial pulsators in the classical instability strip and of various types of eclipsing binaries. The Hipparcos data also provide clear distributions for low-amplitude nonradial pulsators. We show that the preselection of targets for the CoRoT exoplanet programme results in a completely different probability density landscape than the OGLE data, the interpretation of which involves mainly classes of low-amplitude variability in main-sequence stars. Our findings will be incorporated to improve the supervised classification used in the CoRoT catalogue production, once the existence of new classes or subtypes will be confirmed from complementary spectroscopic observations. The CoRoT space mission was developed and is operated by the French space agency CNES, with participation of ESA's RSSD and Science Programmes, Austria, Belgium, Brazil, Germany, and Spain.

  11. Novel corrosion inhibitor technology

    SciTech Connect

    Van de Ven, P.; Fritz, P.; Pellet, R.

    1999-11-01

    A novel, patented corrosion inhibitor technology has been identified for use in heat transfer applications such as automotive and heavy-duty coolant. The new technology is based on a low-toxic, virtually depletion-free carboxylic acid corrosion inhibitor package that performs equally well in mono ethylene glycol and in less toxic propylene glycol coolants. An aqueous inhibitor concentrate is available to provide corrosion protection where freezing protection is not an issue. In the present paper, this inhibitor package is evaluated in the different base fluids: mono ethylene glycol, mono propylene glycol and water. Results are obtained in both standardized and specific corrosion tests as well as in selected field trials. These results indicate that the inhibitor package remains effective and retains the benefits previously identified in automotive engine coolant applications: excellent corrosion protection under localized conditions, general corrosion conditions as well as at high temperature.

  12. CRYSTALLINE SOYBEAN TRYPSIN INHIBITOR

    PubMed Central

    Kunitz, M.

    1947-01-01

    A study has been made of the general properties of crystalline soybean trypsin inhibitor. The soy inhibitor is a stable protein of the globulin type of a molecular weight of about 24,000. Its isoelectric point is at pH 4.5. It inhibits the proteolytic action approximately of an equal weight of crystalline trypsin by combining with trypsin to form a stable compound. Chymotrypsin is only slightly inhibited by soy inhibitor. The reaction between chymotrypsin and the soy inhibitor consists in the formation of a reversibly dissociable compound. The inhibitor has no effect on pepsin. The inhibiting action of the soybean inhibitor is associated with the native state of the protein molecule. Denaturation of the soy protein by heat or acid or alkali brings about a proportional decrease in its inhibiting action on trypsin. Reversal of denaturation results in a proportional gain in the inhibiting activity. Crystalline soy protein when denatured is readily digestible by pepsin, and less readily by chymotrypsin and by trypsin. Methods are given for measuring trypsin and inhibitor activity and also protein concentration with the aid of spectrophotometric density measurements at 280 mµ. PMID:19873496

  13. The intrinsic and interactive effects of RO 15-4513 and ethanol on locomotor activity, body temperature, and blood glucose concentration

    SciTech Connect

    Wood, A.L.; Healey, P.A.; Menendez, J.A.; Verne, S.L.; Atrens, D.M. )

    1989-01-01

    The ability of the putative ethanol antagonist RO 15-4513 to antagonize ethanol-induced hypoactivity, hypothermia and hyperglycemia was investigated in rats. Although RO 15-4513 produced hypoactivity by itself, it attenuated ethanol-induced hypoactivity. This antagonism suggests that ethanol-induced hypoactivity is mediated by the GABA-benzodiazepine receptor complex which is thought to be the site of action of RO 15-4513. In contrast, although RO 15-4513 produced hypothermia by itself, it had no significant effect on ethanol-induced hypothermia. This suggests that the hypothermic effect of ethanol is not mediated by the GABA-benzodiazepine receptor complex. The fact that RO 15-4513, ethanol and the vehicle all produced hyperglycemia suggests a common stress effect and does not permit any firm conclusions to be drawn as to the interaction between ethanol and RO 15-4513 in modulating glycemic responses. These data indicate that the ethanol antagonism of RO 15-4513 is primarily confined to ethanol's behavioral effects and that ethanol's behavioral and physiological effects are mediated by neurochemically distinct mechanisms.

  14. Receptor binding characterization of the benzodiazepine radioligand sup 125 I-Ro16-0154: Potential probe for SPECT (Single Photon Emission Computed Tomography) brain imaging

    SciTech Connect

    Johnson, E.W.; Woods, S.W.; Zoghbi, S.; Baldwin, R.M.; Innis, R.B. ); McBride, B.J. )

    1990-01-01

    The binding of an iodinated benzodiazepine (BZ) radioligand has been characterized, particularly in regard to its potential use as a neuroreceptor brain imaging agent with SPECT (Single Photon Emission Computed Tomography). Ro16-0154 is an iodine-containing BZ antagonist and a close analog of Ro15-1788. In tissue homogenates prepared from human and monkey brain, the binding of {sup 125}I-labeled Ro16-0154 was saturable, of high affinity, and had high ratios of specific to non-specific binding. Physiological concentrations of NaCl enhanced specific binding approximately 15% compared to buffer without this salt. Kinetic studies of association and dissociation demonstrated a temperature dependent decrease in affinity with increasing temperature. Drug displacement studies confirmed that {sup 125}I-Ro16-0154 binds to the central type BZ receptor: binding is virtually identical to that of {sup 3}H-Ro15-1788 except that {sup 125}I-Ro16-0154 shows an almost 10 fold higher affinity at 37{degree}C. These in vitro results suggest that {sup 123}I-labeled Ro16-0154 shows promise as a selective, high affinity SPECT probe of the brain's BZ receptor.

  15. SDN based millimetre wave radio over fiber (RoF) network

    NASA Astrophysics Data System (ADS)

    Amate, Ahmed; Milosavljevic, Milos; Kourtessis, Pandelis; Robinson, Matthew; Senior, John M.

    2015-01-01

    This paper introduces software-defined, millimeter Wave (mm-Wave) networks with Radio over Fiber (RoF) for the delivery of gigabit connectivity required to develop fifth generation (5G) mobile. This network will enable an effective open access system allowing providers to manage and lease the infrastructure to service providers through unbundling new business models. Exploiting the inherited benefits of RoF, complete base station functionalities are centralized at the edges of the metro and aggregation network, leaving remote radio heads (RRHs) with only tunable filtering and amplification. A Software Defined Network (SDN) Central Controller (SCC) is responsible for managing the resource across several mm-Wave Radio Access Networks (RANs) providing a global view of the several network segments. This ensures flexible resource allocation for reduced overall latency and increased throughput. The SDN based mm-Wave RAN also allows for inter edge node communication. Therefore, certain packets can be routed between different RANs supported by the same edge node, reducing latency. System level simulations of the complete network have shown significant improvement of the overall throughput and SINR for wireless users by providing effective resource allocation and coordination among interfering cells. A new Coordinated Multipoint (CoMP) algorithm exploiting the benefits of the SCC global network view for reduced delay in control message exchange is presented, accounting for a minimum packet delay and limited Channel State Information (CSI) in a Long Term Evolution-Advanced (LTE-A), Cloud RAN (CRAN) configuration. The algorithm does not require detailed CSI feedback from UEs but it rather considers UE location (determined by the eNB) as the required parameter. UE throughput in the target sector is represented using a Cumulative Distributive Function (CDF). The drawn characteristics suggest that there is a significant 60% improvement in UE cell edge throughput following the

  16. Chemistry of silica scale mitigation for RO desalination with particular reference to remote operations.

    PubMed

    Milne, Nicholas A; O'Reilly, Tom; Sanciolo, Peter; Ostarcevic, Eddy; Beighton, Mark; Taylor, Kelvin; Mullett, Mark; Tarquin, Anthony J; Gray, Stephen R

    2014-11-15

    Silica scaling in reverse osmosis of groundwater is a significant issue in water stressed areas due to the limitations that scaling imposes on water recovery. While calcium and magnesium scaling potential can be significantly reduced by the use of ion exchange or other softening processes, the silica scaling potential typically remains. Improving the recovery of reverse osmosis by limiting the potential for silica scale is important in ensuring maximum water recovery. This is particularly important for mining and natural gas industries that are located in remote regions. The remote nature of these sites imposes three major restrictions on the silica scale mitigation process. Firstly, the generation of poorly dewaterable sludges must be avoided. Also, the quality of any reverse osmosis (RO) permeate must be able to meet the end use requirements, particularly for boilers. Finally, silica removal should not impact upon other potentially useful or valuable components within the brine, and should not make the disposal of the unusable waste brine components more difficult. Reduction of scaling potential can be achieved in three main ways: operating RO at high pH after hardness has been removed, operating at low pH, and reducing the silica concentration either in pretreatment or by using an interstage technique. Operating at high pH has the initial requirement of hardness removal to prevent scaling and this could be an issue on some sites. Hardness removal operations that use ion exchange resins may be challenged by water chemistry and the operational costs associated with high chemical regeneration costs. Operating at low pH may be more desirable than high pH operation as this can help to reduce the risk of scale formation from calcium or magnesium salts. The drawback comes from the cost of acid, particularly for high-alkalinity waters. There are numerous silica removal techniques including chemical dosing of lime, or aluminium or iron salts, electrocoagulation

  17. AST/RO Observations of CO J=7-6 Emission from the Galactic Center

    NASA Astrophysics Data System (ADS)

    Kim, S.; Martin, C. L.; Stark, A. A.; Lane, A. P.

    2000-12-01

    We present a map of the Galactic Center region in the CO J=7-6 transition observed with the Antarctic Submillimeter Telescope and Remote Observatory (AST/RO) located at Amundsen-Scott South Pole Station. Emission from the 809 GHz J=7-6 transition of 12CO was mapped over the region -2.7 < l < 3.6, -1.0 < b < 1.0, on a 1' grid with a spatial resolution of ~ 85''. The CO J=4-3 and [CI] emissions from this region have been mapped with AST/RO by Martin et al. (2001) and Ojha et al. (2000). These two spectral lines are distributed throughout the Galactic Center region in a manner almost identical to that of CO J=1-0; the CO(4-3)/ CO(1-0) line ratio and the [CI]/CO line ratios are remarkably uniform across a wide variety of Galactic Center features. In contrast, the CO J=7-6 emission from the Galactic Center region is confined to the Sgr A and Sgr B2 complexes. The implication is that the photon-dominated regions surrounding the Galactic Center are remarkably similar in mean density and kinetic temperature at n = 3000 cm-3 and T = 35 K, except for the two special regions Sgr A and Sgr B2, which are denser. The CO(7-6)/CO(4-3) line temperature ratios near Sgr B2 are similar to those observed in the nuclear region of the starburst galaxy M82 (Mao et al. 2000), while the CO(7-6)/CO(4-3) line temperature ratios around Sgr A are a factor of three lower than those near Sgr B2. The CO(7-6)/CO(4-3) line ratio in the Galactic Center region as a whole is at least an order of magnitude less than that in a comparable region near the center of M82. This research was supported in part by the National Science Foundation under a cooperative agreement with the Center for Astrophysical Research in Antarctica (CARA), grant number NSF OPP 89-20223. CARA is a National Science Foundation Science and Technology Center.

  18. Disentangling planetary and stellar activity features in the CoRoT-2 light curve

    NASA Astrophysics Data System (ADS)

    Bruno, G.; Deleuil, M.; Almenara, J.-M.; Barros, S. C. C.; Lanza, A. F.; Montalto, M.; Boisse, I.; Santerne, A.; Lagrange, A.-M.; Meunier, N.

    2016-11-01

    Aims: Stellar activity is an important source of systematic errors and uncertainties in the characterization of exoplanets. Most of the techniques used to correct for this activity focus on an ad hoc data reduction. Methods: We have developed a software for the combined fit of transits and stellar activity features in high-precision long-duration photometry. Our aim is to take advantage of the modelling to derive correct stellar and planetary parameters, even in the case of strong stellar activity. Results: We use an analytic approach to model the light curve. The code KSint, modified by adding the evolution of active regions, is implemented into our Bayesian modelling package PASTIS. The code is then applied to the light curve of CoRoT-2. The light curve is divided in segments to reduce the number of free parameters needed by the fit. We perform a Markov chain Monte Carlo analysis in two ways. In the first, we perform a global and independent modelling of each segment of the light curve, transits are not normalized and are fitted together with the activity features, and occulted features are taken into account during the transit fit. In the second, we normalize the transits with a model of the non-occulted activity features, and then we apply a standard transit fit, which does not take the occulted features into account. Conclusions: Our model recovers the activity features coverage of the stellar surface and different rotation periods for different features. We find variations in the transit parameters of different segments and show that they are likely due to the division applied to the light curve. Neglecting stellar activity or even only bright spots while normalizing the transits yields a 1.2σ larger and 2.3σ smaller transit depth, respectively. The stellar density also presents up to 2.5σ differences depending on the normalization technique. Our analysis confirms the inflated radius of the planet (1.475 ± 0.031RJ) found by other authors. We show that

  19. Variational Calculations of IR Ro-Vibrational Spectra for Nitric Acid

    NASA Astrophysics Data System (ADS)

    Pavlyuchko, A. I.; Yurchenko, S. N.; Tennyson, J.

    2013-09-01

    To model the atmospheric composition of the potentially habitable planets, it is essential to have comprehensive data on the spectroscopic properties of the main molecular absorbers. This is especially true in the infrared region which is dominated by transitions of polyatomic molecules [1]. Nitric acid (HNO3) is an important constituent of the Earth atmosphere where it is a prominent bio-signature. Here we present simulations of the absorption spectra for HNO3. We have developed a variational method to solve the ro-vibrational Schrödinger equation for a general polyatomic molecule. The ro-vibrational Hamiltonian is given by [2] where the internal curvilinear vibrational coordinates qi are used to represent the displacements of the bond lengths and bond angles, ?ij(q) are elements of the matrix of the kinematic coefficients, t is the determinant of this matrix, 'a are the Euler angles, and μab(q) is the inverse matrix of the tensor of inertia. The potential energy function, V (q), is given by a fourthorder polynomial expansion in terms of Morse variables xi = 1 - e-iqi for the stretching coordinates and xi = qi for the bending coordinates. The dipole moment of the molecule is presented in the form of a Taylor series of the 2nd order in terms of qi. The parameters of the potential energy and the dipole moment functions of HNO3 were calculated by the quantum chemical method at the CCSD(T)/aug-cc-pVQZ level of theory. With this potential energy function, agreement between the calculated and experimental fundamental frequencies of vibrations is within 5 cm -1. The harmonic part of the potential function was then optimized by fitting to the experimental fundamental frequencies and used to simulate the IR spectra of HNO3. The results are in good agreement with the experimental data. The figure shows an example of the simulated spectra of HNO3 in the area of the strong Fermi resonance between the -5 and 2-9 bands along with an experimental counterpart. The resulting

  20. The roAp star α Circinus as seen by BRITE-Constellation

    NASA Astrophysics Data System (ADS)

    Weiss, W. W.; Fröhlich, H.-E.; Pigulski, A.; Popowicz, A.; Huber, D.; Kuschnig, R.; Moffat, A. F. J.; Matthews, J. M.; Saio, H.; Schwarzenberg-Czerny, A.; Grant, C. C.; Koudelka, O.; Lüftinger, T.; Rucinski, S. M.; Wade, G. A.; Alves, J.; Guedel, M.; Handler, G.; Mochnacki, St.; Orleanski, P.; Pablo, B.; Pamyatnykh, A.; Ramiaramanantsoa, T.; Rowe, J.; Whittaker, G.; Zawistowski, T.; Zocłońska, E.; Zwintz, K.

    2016-04-01

    We report on an analysis of high-precision, multi-colour photometric observations of the rapidly-oscillating Ap (roAp) star α Cir. These observations were obtained with the BRITE-Constellation, which is a coordinated mission of five nanosatellites that collects continuous millimagnitude-precision photometry of dozens of bright stars for up to 180 days at a time in two colours (≈Johnson B and R). BRITE stands for BRight Target Explorer. The object α Cir is the brightest roAp star and an ideal target for such investigations, facilitating the determination of oscillation frequencies with high resolution. This star is bright enough for complementary interferometry and time-resolved spectroscopy. Four BRITE satellites observed α Cir for146 d or 33 rotational cycles. Phasing the photometry according to the 4.4790 d rotational period reveals qualitatively different light variations in the two photometric bands. The phased red-band photometry is in good agreement with previously-published WIRE data, showing a light curve symmetric about phase 0.5 with a strong contribution from the first harmonic. The phased blue-lband data, in contrast, show an essentially sinusoidal variation. We model both light curves with Bayesian Photometric Imaging, which suggests the presence of two large-scale, photometrically bright (relative to the surrounding photosphere) spots. We also examine the high-frequency pulsation spectrum as encoded in the BRITE photometry. Our analysis establishes the stability of the main pulsation frequency over the last ≈20 yr, confirms the presence of frequency f7, which was not detected (or the mode not excited) prior to 2006, and excludes quadrupolar modes for the main pulsation frequency. Based on data collected by the BRITE-Constellation satellite mission, built, launched and operated thanks to support from the Austrian Aeronautics and Space Agency, the University of Vienna, the Canadian Space Agency (CSA), the Foundation for Polish Science

  1. Standardization of vitrinite reflectance measurements in shale petroleum systems: How accurate are my Ro data?

    USGS Publications Warehouse

    Hackley, Paul C.

    2014-01-01

    Vitrinite reflectance generally is considered the most robust thermal maturity parameter available for application to hydrocarbon exploration and petroleum system evaluation. However, until 2011 there was no standardized methodology available to provide guidelines for vitrinite reflectance measurements in shale. Efforts to correct this deficiency resulted in publication of ASTM D7708-11: Standard test method for microscopical determination of the reflectance of vitrinite dispersed in sedimentary rocks. In 2012-2013, an interlaboratory exercise was conducted to establish precision limits for the measurement technique. Six samples, representing a wide variety of shale, were tested in duplicate by 28 analysts in 22 laboratories from 14 countries. Samples ranged from immature to overmature (Ro 0.31-1.53%), from organic-rich to organic-lean (1-22 wt.% total organic carbon), and contained Type I (lacustrine), Type II (marine), and Type III (terrestrial) kerogens. Repeatability values (difference between repetitive results from same operator, same conditions) ranged from 0.03-0.11% absolute reflectance, whereas reproducibility values (difference between results obtained on same test material by different operators, different laboratories) ranged from 0.12-0.54% absolute reflectance. Repeatability and reproducibility degraded consistently with increasing maturity and decreasing organic content. However, samples with terrestrial kerogens (Type III) fell off this trend, showing improved levels of reproducibility due to higher vitrinite content and improved ease of identification. Operators did not consistently meet the reporting requirements of the test method, indicating that a common reporting template is required to improve data quality. The most difficult problem encountered was the petrographic distinction of solid bitumens and low-reflecting inert macerals from vitrinite when vitrinite occurred with reflectance ranges overlapping the other components. Discussion among

  2. Isolation and characterization of a cDNA clone encoding the 60-kD component of the human SS-A/Ro ribonucleoprotein autoantigen.

    PubMed Central

    Ben-Chetrit, E; Gandy, B J; Tan, E M; Sullivan, K F

    1989-01-01

    SS-A/Ro is a nucleocytoplasmic ribonucleoprotein (RNP) particle that is a common target of autoimmune response in Sjögren's syndrome (SS) and systemic lupus erythematosus (SLE). Previously, SS-A/Ro has been shown to be composed of at least two polypeptide antigens of 60 and 52 kD noncovalently associated with a set of small RNAs, designated Y1-Y5. A serum from an SS patient was selected to screen a lambda gt11 cDNA library constructed from human T cell lymphoblastic leukemia (MOLT-4) mRNA. An immunoreactive clone was isolated that possessed a 1.8-kb cDNA insert. In vitro transcription and translation of the cDNA resulted in the synthesis of a 57.5-kD polypeptide which was specifically immunoprecipitated by SS-A/Ro antisera. The identity of the cDNA encoded protein as the 60-kD SS-A/Ro antigen was established by proteolytic peptide mapping of the cDNA-encoded protein and the 60-kD HeLa cell antigen. The sequence of the cDNA shows that the 60-kD SS-A/Ro protein possesses both RNA binding protein consensus sequences and a single zinc-finger motif. Recombinant SS-A/Ro antigen produced in bacteria proved to be a sensitive and specific reagent for detection of anti-SS-A/Ro antibodies in patient sera. The availability of the 60-kD SS-A/Ro cDNA will enable detailed analysis of the molecular structure and function of the SS-A/Ro RNP particle and its role in autoimmune pathology. Images PMID:2649513

  3. Astrobiology Road Mapping (AstRoMap) - A project within FP7 of the European Commission: First results

    NASA Astrophysics Data System (ADS)

    Gomez-Gomez, Felipe; Capria, Maria Teresa; Palomba, Ernesto; Walter, Nicolas; Rettberg, Petra; Muller, Christian; Horneck, Gerda

    AstRoMap (Astrobiology and Planetary Exploration Road Mapping) is a funded project formulated in the 5th Call of the European Commission FP7 framework. The main objectives of the AstRoMap are: 1. Identify the main astrobiology issues to be addressed by Europe in the next decades in relation with space exploration 2. Identify potential mission concepts that would allow addressing these issues 3. Identify the technology developments required to enable these missions 4. Provide a prioritized roadmap integrating science and technology activities as well as ground-based approach 5. Map scientific knowledge related to astrobiology in Europe To reach those objectives, AstRoMap is executed within the following steps: 1. Community consultation. In order to map the European astrobiology landscape and to provide a collaborative networking platform for this community, the AstRoMap project hosts a database of scientists (European and beyond) interested in astrobiology and planetary exploration (see: http://www.astromap.eu/database.html). It reflects the demography and the research and teaching activities of the astrobiology community, as well as their professional profiles and involvement in astrobiology projects. Considering future aspects of astrobiology in Europe, the need for more astrobiology-dedicated funding programmes at the EU level, especially for cross-disciplinary groups, was stressed. This might eventually lead to the creation of a European laboratory of Astrobiology, or even of a European Astrobiology Institute. 2. Workshops organisation. On the basis of the feedbacks from the community consultation, the potential participants and interesting topics are being identified to take part in the following workshops: 1-. Origin of organic compounds, steps to life; 2. Physico-chemical boundary conditions for habitability 3. Biosignatures as facilitating life detection 4. Origin of the Solar system 3. Astrobiology road-mapping. Based on the results and major conclusions

  4. Revisiting CoRoT RR Lyrae stars: detection of period doubling and temporal variation of additional frequencies

    NASA Astrophysics Data System (ADS)

    Szabó, R.; Benkő, J. M.; Paparó, M.; Chapellier, E.; Poretti, E.; Baglin, A.; Weiss, W. W.; Kolenberg, K.; Guggenberger, E.; Le Borgne, J.-F.

    2014-10-01

    Context. High-precision, space-based photometric missions like CoRoT and Kepler have revealed new and surprising phenomena in classical variable stars. Such discoveries were the period doubling in RR Lyrae stars and the frequent occurrence of additional periodicities some of which can be explained by radial overtone modes, but others are discordant with the radial eigenfrequency spectrum. Aims: We search for signs of period doubling in CoRoT RR Lyrae stars. The occurrence of this dynamical effect in modulated RR Lyrae stars might help us to gain more information about the mysterious Blazhko effect. The temporal variability of the additional frequencies in representatives of all subtypes of RR Lyrae stars is also investigated. Methods: We preprocess CoRoT light curves by applying trend and jump correction and outlier removal. Standard Fourier technique is used to analyze the frequency content of our targets and follow the time-dependent phenomena. Results: The most comprehensive collection of CoRoT RR Lyrae stars, including new discoveries is presented and analyzed. We found alternating maxima and in some cases half-integer frequencies in four CoRoT Blazhko RR Lyrae stars, as clear signs of the presence of period doubling. This reinforces that period doubling is an important ingredient for understanding the Blazhko effect - a premise we derived previously from the Kepler RR Lyrae sample. As expected, period doubling is detectable only for short time intervals in most modulated RRab stars. Our results show that the temporal variability of the additional frequencies in all RR Lyrae subtypes is ubiquitous. The ephemeral nature and the highly variable amplitude of these variations suggest a complex underlying dynamics of and an intricate interplay between radial and possibly nonradial modes in RR Lyrae stars. The omnipresence of additional modes in all types of RR Lyrae - except in non-modulated RRab stars - implies that asteroseismology of these objects should be

  5. Accretion dynamics and disk evolution in NGC 2264: a study based on CoRoT photometric observations

    NASA Astrophysics Data System (ADS)

    Alencar, S. H. P.; Teixeira, P. S.; Guimarães, M. M.; McGinnis, P. T.; Gameiro, J. F.; Bouvier, J.; Aigrain, S.; Flaccomio, E.; Favata, F.

    2010-09-01

    Context. The young cluster NGC 2264 was observed with the CoRoT satellite for 23 days uninterruptedly in March 2008 with unprecedented photometric accuracy. We present the first results of our analysis of the accreting population belonging to the cluster as observed by CoRoT. Aims: We search for possible light curve variability of the same nature as that observed in the classical T Tauri star AA Tau, which was attributed to a magnetically controlled inner disk warp. The inner warp dynamics is supposed to be directly associated with the interaction between the stellar magnetic field and the inner disk region. Methods: We analyzed the CoRoT light curves of 83 previously known classical T Tauri stars that belong to NGC 2264 classifying them according to their light-curve morphology. We also studied the CoRoT light-curve morphology as a function of a Spitzer-based classification of the star-disk systems. Results: The classification derived on the basis of the CoRoT light-curve morphology agrees very well with the Spitzer IRAC-based classification of the systems. The percentage of AA Tau-like light curves decreases as the inner disk dissipates, from 40% ± 10% in systems with thick inner disks to 36% ± 16% in systems with anemic disks and zero in naked photosphere systems. Indeed, 91% ± 29% of the CTTS with naked photospheres exhibit pure spot-like variability, while only 18% ± 7% of the thick disk systems do so, presumably those seen at low inclination and thus free of variable obscuration. Conclusions: AA Tau-like light curves are found to be fairly common, with a frequency of at least ~30 to 40% in young stars with inner dusty disks. The temporal evolution of the light curves indicates that the structure of the inner disk warp, located close to the corotation radius and responsible for the obscuration episodes, varies over a timescale of a few (~1-3) rotational periods. This probably reflects the highly dynamical nature of the star-disk magnetospheric interaction

  6. New RO TFC Membranes by Interfacial Polymerization in n-Dodecane with Various co-Solvents

    PubMed Central

    Al-Hobaib, Abdullah Sulaiman; Al-Suhybani, Mohammed Sulaiman; Al-Sheetan, Khalid Mohammed; Mousa, Hasan; Shaik, Mohammed Rafi

    2016-01-01

    The objective of this research is to prepare and characterize a new and highly efficient polyamide TFC RO membrane by interfacial polymerization in dodecane solvent mixed with co-solvents. Three co-solvents were tested namely; acetone, ethyl acetate, and diethyl ether of concentration of 0.5, 1, 2, 3, and 5 wt %. The modified membranes were characterized by SEM, EDX, AFM and contact angle techniques. The results showed that addition of co-solvent results in a decrease in the roughness, pore size and thickness of the produced membranes. However, as the concentration of the co-solvent increases the pore size of the membranes gets larger. Among the three co-solvents tested, acetone was found to result in membranes with the largest pore size and contact angle followed by diethyl ether then ethyl acetate. Measured contact angle increases as the concentration of the co-solvent increases reaching a constant value except for ethyl acetate where it was found to drop. Investigating flux and salt rejection by the formulated membranes showed that higher flux was attained when acetone was used as a co-solvent followed by diethyl ether then ethyl acetate. However, the highest salt rejection was achieved with diethyl ether. PMID:27136591

  7. AST/RO Observations of CO (J=7-6) Emission in NGC 6334

    NASA Astrophysics Data System (ADS)

    Kim, S.; Lane, A. P.; Stark, A. A.; Martin, C. L.; Narayanan, D.; Yan, M.

    2002-05-01

    We present maps of the massive, southern star-forming region NGC6334 in the CO (J=7-6), CO (J=4-3), and 809 GHz [CI] transitions. These lines were observed with the Antarctic Submillimeter Telescope and Remote Observatory (AST/RO) located at Amundsen-Scott South Pole Station. We find two high-excitation CO components on either side of the X-ray emission peak mapped with ASCA (Sekimoto et al. 2000). Our Large Velocity Gradient (LVG) excitation analysis of the line intensity ratios indicates that the photon-dominated regions in NGC6334 have densities of n(H2) ~ 10(3.9-4.2) cm-3 and kinetic temperatures of T{ k} ~ 25-55 K. With these physical parameters in conjunction with our previously observed 492 GHz [CI] line map, we will discuss a thermal chemical photodissociation model of gas clouds around star forming sites in NGC 6334. This research was supported by the National Science Foundation under a cooperative agreement with the Center for Astrophysical Research in Antarctica (CARA), grant NSF OPP 89-20223. CARA is a National Science Foundation Science and Technology Center.

  8. New RO TFC Membranes by Interfacial Polymerization in n-Dodecane with Various co-Solvents.

    PubMed

    Al-Hobaib, Abdullah Sulaiman; Al-Suhybani, Mohammed Sulaiman; Al-Sheetan, Khalid Mohammed; Mousa, Hasan; Shaik, Mohammed Rafi

    2016-04-29

    The objective of this research is to prepare and characterize a new and highly efficient polyamide TFC RO membrane by interfacial polymerization in dodecane solvent mixed with co-solvents. Three co-solvents were tested namely; acetone, ethyl acetate, and diethyl ether of concentration of 0.5, 1, 2, 3, and 5 wt %. The modified membranes were characterized by SEM, EDX, AFM and contact angle techniques. The results showed that addition of co-solvent results in a decrease in the roughness, pore size and thickness of the produced membranes. However, as the concentration of the co-solvent increases the pore size of the membranes gets larger. Among the three co-solvents tested, acetone was found to result in membranes with the largest pore size and contact angle followed by diethyl ether then ethyl acetate. Measured contact angle increases as the concentration of the co-solvent increases reaching a constant value except for ethyl acetate where it was found to drop. Investigating flux and salt rejection by the formulated membranes showed that higher flux was attained when acetone was used as a co-solvent followed by diethyl ether then ethyl acetate. However, the highest salt rejection was achieved with diethyl ether.

  9. The ro-vibrational `conveyor belt' for all-optical lasing during laser filamentation in Nitrogen

    NASA Astrophysics Data System (ADS)

    Ivanov, Misha; Richter, Maria; Morales, Felipe; Smirnova, Olga

    2016-05-01

    Inducing and controlling lasing in the open air is an intriguing challenge. Recent experiments on laser filamentation in the air have demonstrated generation of population inversion and lasing on the 391 nm line in the nitrogen ion, which corresponds to the transition between its second excited B2Σu+ and the ground X2Σg+ electronic states. Importantly, lasing at this transition appears to be a very general effect, arising during filamentation of virtually any incident radiation, from visible to mid-infrared. We analyze the possible mechanisms that can be responsible for the generation of the population inversion between the B2Σu+ and X2Σg+ states of N2+,focusing on the interplay between tunnel ionization of neutral nitrogen to different electronic states, ultrafast laser driven electronic excitations in the ion, molecular vibrations, laser induced alignment and rotations. We show how the strong laser field creates a ro-vibrational `conveyor belt' carrying the population away from the ground electronic state X2Σg+ and enabling population inversion in B2Σu+ . We show that this mechanism is robust with respect to the incident laser wavelength, and analyze its optimization with respect to the fundamental wavelength and pulse duration.

  10. Thermal maturity patterns in New York State using CAI and %Ro

    USGS Publications Warehouse

    Weary, D.J.; Ryder, R.T.; Nyahay, R.E.

    2001-01-01

    New conodont alteration index (CAI) and vitrinite reflectance (%Ro) data collected from drill holes in the Appalachian basin of New York State allow refinement of thermal maturity maps for Ordovician and Devonian rocks. CAI isotherms on the new maps show a pattern that approximates that published by Harris et al. (1978) in eastern and western New York, but it differs in central New York, where the isotherms are shifted markedly westward by more than 100 km and are more tightly grouped. This close grouping of isograds reflects a steeper thermal gradient than previously noted by Harris et al. (1978) and agrees closely with the abrupt west-to-east increase in thermal maturity across New York noted by Johnsson (1986). These data show, in concordance with previous studies, that thermal maturity levels in these rocks are higher than can be explained by simple burial heating beneath the present thickness of overburden. The Ordovician and Devonian rocks of the Appalachian Basin in New York must have been buried by very thick post-Devonian sediments (4-6 km suggested by Sarwar and Friedman 1995) or were exposed to a higher-than-normal geothermal flux caused by crustal extension, or a combination of the two.

  11. Synergies of CoRoT asteroseismology and APOGEE spectroscopy -- Applications to Galactic Archaeology

    NASA Astrophysics Data System (ADS)

    Anders, Friedrich; Chiappini, Cristina; Silva Rodrigues, Thaíse; Miglio, Andrea; Montalbàn, Josefina; Mosser, Benoit; Girardi, Leo; Valentini, Marica; Steinmetz, Matthias

    2015-08-01

    We present the first coherent dataset of 678 solar-like oscillating CoRoT red-giant stars located in two fields of the Galactic disc which have been followed up spectroscopically by the Apache Point Observatory Galactic Evolution Experiment (APOGEE).For the first time in a homogeneous analysis, ages and chemical abundance patterns of field stars have been measured over a largeradial range of the Milky Way's disc (4.5 kpc

  12. Detecting planets in Kepler lightcurves using methods developed for CoRoT.

    NASA Astrophysics Data System (ADS)

    Grziwa, S.; Korth, J.; Pätzold, M.

    2011-10-01

    Launched in March 2009, Kepler is the second space telescope dedicated to the search for extrasolar planets. NASA released 150.000 lightcurves to the public in 2010 and announced that Kepler has found 1.235 candidates. The Rhenish Institute for Environmental Research (RIU-PF) is one of the detection groups from the CoRoT space mission. RIU-PF developed the software package EXOTRANS for the detection of transits in stellar lightcurves. EXOTRANS is designed for the fast automated processing of huge amounts of data and was easily adapted to the analysis of Kepler lightcurves. The use of different techniques and philosophies helps to find more candidates and to rule out others. We present the analysis of the Kepler lightcurves with EXOTRANS. Results of our filter (trend, harmonic) and detection (dcBLS) techniques are compared with the techniques used by Kepler (PDC, TPS). The different approaches to rule out false positives are discussed and additional candidates found by EXOTRANS are presented.

  13. A European Roadmap for Research in Astrobiology - The AstRoMap Roadmap

    NASA Astrophysics Data System (ADS)

    Gómez, F.; Walter, N.; Horneck, G.; Muller, C.; Rettberg, P.; Capria, M.; Palomba, E.

    2015-10-01

    AstRoMap (Astrobiology Road Mapping activity-www.astromap-eu.org) is a collaborative project which will provide the European Planetary Science Community with a road map in astrobiology. The goals of the project have been: (i) to pose big questions related to astrobiology; and (ii) the identification of experiments, new technology and/or those space missions to be developed in future programs and which could answer those big questions. This collaborative infrastructure includes the organization of expert panels and international workshops in order to discuss about those big questions and the science objectives by the community to be addressed. The main deliverable will be a Roadmap document. The project is steered by a consortium of six European and national research institutes and associations: -­- Centro de Astrobiologica (INTACSIC), Spain -­- European Science Foundation, France -­- Association pour un Réseau Européen d'Exo/Astrobiology (EANA), France -­- B-USOC, Belgium -­- Deutsches Zentrum für Luft- und Raumfahrt (DLR), Germany -­- National Institute for Astrophysics (INAF), ItalyOrigin and evolution of planetary systems -­- Origin of organic compounds in space -­- Rock-water-carbon interactions, organic synthesis, and steps to life -­- Life and habitability on Earth and in Space -­- -­- Biosignatures as facilitating life detection The key topics will focus on a limited number of strategic scientific objectives to be addressed in the next 20 years by European astrobiologists, and suggest research activities for future development.

  14. Toward black-box-type full- and reduced-dimensional variational (ro)vibrational computations

    NASA Astrophysics Data System (ADS)

    Mátyus, Edit; Czakó, Gábor; Császár, Attila G.

    2009-04-01

    A black-box-type algorithm is presented for the variational computation of energy levels and wave functions using a (ro)vibrational Hamiltonian expressed in an arbitrarily chosen body-fixed frame and in any set of internal coordinates of full or reduced vibrational dimensionality. To make the required numerical work feasible, matrix representation of the operators is constructed using a discrete variable representation (DVR). The favorable properties of DVR are exploited in the straightforward and numerically exact inclusion of any representation of the potential and the kinetic energy including the G matrix and the extrapotential term. In this algorithm there is no need for an a priori analytic derivation of the kinetic energy operator, as all of its matrix elements at each grid point are computed numerically either in a full- or a reduced-dimensional model. Due to the simple and straightforward definition of reduced-dimensional models within this approach, a fully anharmonic variational treatment of large, otherwise intractable molecular systems becomes available. In the computer code based on the above algorithm, there is no inherent limitation for the maximally coupled number of vibrational degrees of freedom. However, in practice current personal computers allow the treatment of about nine fully coupled vibrational dimensions. Computation of vibrational band origins of full and reduced dimensions showing the advantages and limitations of the algorithm and the related computer code are presented for the water, ammonia, and methane molecules.

  15. A FFT Method for the Quasiclassical Selection of Initial Ro-Vibrational States of Triatomic Molecules

    NASA Technical Reports Server (NTRS)

    Eaker, Charles W.; Schwenke, David W.; Langhoff, Stephen R. (Technical Monitor)

    1995-01-01

    This paper describes the use of an exact fast Fourier transform (FFT) method to prepare specified vibrational-rotational states of triatomic molecules. The method determines the Fourier coefficients needed to describe the coordinates and momenta of a vibrating-rotating triatomic molecule. Once the Fourier coefficients of a particular state are determined, it is possible to easily generate as many random sets of initial cartesian coordinates and momenta as desired. All the members of each set will correspond to the particular vibrational-rotational state selected. For example, in the case of the ground vibrational state of a non-rotating water molecule, the calculated actions of 100 sets of initial conditions produced actions within 0.001 h(bar) of the specified quantization values and energies within 5 cm(sup -1) of the semiclassical eigenvalue. The numerical procedure is straightforward for states in which all the fundamental frequencies are independent. However for states for which the fundamental frequencies become commensurate (resonance states), there are additional complications. In these cases it is necessary to determine a new set of "fundamental" frequencies and to modify the quantization conditions. Once these adjustments are made, good results are obtained for resonance states. The major problems are in labelling the large number of Fourier coefficients and the presence of regions of chaotic motion. Results are presented for the vibrational states of H2O and HCN and the ro-vibrational states of H2O.

  16. KIC 7582608: a new Kepler roAp star with frequency variability

    NASA Astrophysics Data System (ADS)

    Holdsworth, D. L.; Smalley, B.; Kurtz, D. W.; Southworth, J.; Cunha, M. S.; Clubb, K. I.

    2015-09-01

    We analyse the fifth roAp star reported in the Kepler field, KIC 7582608, discovered with the SuperWASP project. The object shows a high frequency pulsation at 181.7324d-1 (P = 7.9 min) with an amplitude of 1.45 mmag, and low frequency rotational modulation corresponding to a period of 20.4339 d. Spectral analysis confirms the Ap nature of the target, with characteristic lines of rare earth elements present. From our spectral observations we derive a lower limit on the mean magnetic field modulus of =3.05 ± 0.23 kG. Long Cadence Kepler observations show a frequency quintuplet split by the rotational period of the star, typical for an oblique pulsator. We suggest the star is a quadrupole pulsator with a geometry such that i ~ 66° and β ~ 33°. We detect frequency variations of the pulsation in both the WASP and Kepler data sets on many time scales. Linear, non-adiabatic stability modelling allows us to constrain a region on the HR diagram where the pulsations are unstable, an area consistent with observations.

  17. RoPEUS: A New Robust Algorithm for Static Positioning in Ultrasonic Systems

    PubMed Central

    Prieto, José Carlos; Croux, Christophe; Jiménez, Antonio Ramón

    2009-01-01

    A well known problem for precise positioning in real environments is the presence of outliers in the measurement sample. Its importance is even bigger in ultrasound based systems since this technology needs a direct line of sight between emitters and receivers. Standard techniques for outlier detection in range based systems do not usually employ robust algorithms, failing when multiple outliers are present. The direct application of standard robust regression algorithms fails in static positioning (where only the current measurement sample is considered) in real ultrasound based systems mainly due to the limited number of measurements and the geometry effects. This paper presents a new robust algorithm, called RoPEUS, based on MM estimation, that follows a typical two-step strategy: 1) a high breakdown point algorithm to obtain a clean sample, and 2) a refinement algorithm to increase the accuracy of the solution. The main modifications proposed to the standard MM robust algorithm are a built in check of partial solutions in the first step (rejecting bad geometries) and the off-line calculation of the scale of the measurements. The algorithm is tested with real samples obtained with the 3D-LOCUS ultrasound localization system in an ideal environment without obstacles. These measurements are corrupted with typical outlying patterns to numerically evaluate the algorithm performance with respect to the standard parity space algorithm. The algorithm proves to be robust under single or multiple outliers, providing similar accuracy figures in all cases. PMID:22408522

  18. A Study of Ro-vibrational OH Emission from Herbig Ae/Be Stars

    NASA Astrophysics Data System (ADS)

    Brittain, Sean D.; Najita, Joan R.; Carr, John S.; Ádámkovics, Máté; Reynolds, Nickalas

    2016-10-01

    We present a study of ro-vibrational OH and CO emission from 21 disks around Herbig Ae/Be stars. We find that the OH and CO luminosities are proportional over a wide range of stellar ultraviolet luminosities. The OH and CO line profiles are also similar, indicating that they arise from roughly the same radial region of the disk. The CO and OH emission are both correlated with the far-ultraviolet luminosity of the stars, while the polycyclic aromatic hydrocarbon (PAH) luminosity is correlated with the longer wavelength ultraviolet luminosity of the stars. Although disk flaring affects the PAH luminosity, it is not a factor in the luminosity of the OH and CO emission. These properties are consistent with models of UV-irradiated disk atmospheres. We also find that the transition disks in our sample, which have large optically thin inner regions, have lower OH and CO luminosities than non-transition disk sources with similar ultraviolet luminosities. This result, while tentative given the small sample size, is consistent with the interpretation that transition disks lack a gaseous disk close to the star.

  19. Pole STAR: An 810 GHz Array Receiver for AST/RO

    NASA Astrophysics Data System (ADS)

    Groppi, C.; Walker, C.; Hungerford, A.; Kulesa, C.; Jacobs, K.; Kooi, J.

    We are constructing a 4-channel receiver at 810 GHz for use on the Antarctic Submillimeter Telescope and Remote Observatory located at the South Pole (AST/RO). The 810 GHz mixers and junctions for the array are being provided by KOSMA. The mixers are housed in a hybrid cryostat located in a warm Coude' room just below the 1.7 m telescope. A pair of parabolic mirrors will be used to reimage the telescope's focal plane through a Martin-Puplett LO diplexer onto a 2x2 array of lenses. The lenses efficiently couple the telescope to each mixer's corrugated feedhorn. The SIS junction is matched to the waveguide by an on-chip tuner and a single, fixed backshort. The 1-2 GHz IF output of each mixer is fed into a low-noise, balanced, HEMT amplifier. All bias signals are provided by a computer controlled bias system, which is fully optically isolated from the control computer. This system provides automated adjustment and optimization of bias levels with web based monitoring. The IF outputs are further processed at room temperature and fed into a 4-channel array AOS constructed by KOSMA. A Gunn oscillator (J. Carlstrom) and multiplier (Erickson & Narayanan) are used to drive the array.

  20. The changing phases of extrasolar planet CoRoT-1b.

    PubMed

    Snellen, Ignas A G; de Mooij, Ernst J W; Albrecht, Simon

    2009-05-28

    Hot Jupiters are a class of extrasolar planet that orbit their parent stars at very short distances. They are expected to be tidally locked, which can lead to a large temperature difference between their daysides and nightsides. Infrared observations of eclipsing systems have yielded dayside temperatures for a number of transiting planets. The day-night contrast of the transiting extrasolar planet HD 189733b was 'mapped' using infrared observations. It is expected that the contrast between the daysides and nightsides of hot Jupiters is much higher at visual wavelengths, shorter than that of the peak emission, and could be further enhanced by reflected stellar light. Here we report the analysis of optical photometric data obtained over 36 planetary orbits of the transiting hot Jupiter CoRoT-1b. The data are consistent with the nightside hemisphere of the planet being entirely black, with the dayside flux dominating the optical phase curve. This means that at optical wavelengths the planet's phase variation is just as we see it for the interior planets in the Solar System. The data allow for only a small fraction of reflected light, corresponding to a geometric albedo of <0.20.

  1. Massive spectroscopic analysis of the stellar populations in three of the CoRoT/Exoplanet fields

    NASA Astrophysics Data System (ADS)

    Gazzano, J.-C.; Deleuil, M.; de Laverny, P.; Kordopatis, G.; Moutou, C.; Recio-Blanco, A.; Bijaoui, A.; Bouchy, F.; Ordenovic, C.

    2010-12-01

    We derived the atmospheric parameters (teff, logg, met, alf), řad, and šini for 1227 CoRoT/Exoplanet targets in three of the fields observed by CoRoT. We derived the corresponding absolute magnitude using evolutionary models. We combined 2MASS colours with a new implementation of the infrared flux method, and the teff from matisse to constrain the interstellar extinction. These steps allowed us to measure the stellar distances, hence deriving kinematics information. This opened the path to the study of the stellar populations found in these \\corot fields.These studies showed the potential of combining a multi-fiber instrument like FLAMES/GIRAFFE, with an automatic tool to determine efficiently atmospheric stellar parameters, as MATISSE.

  2. Ro 15-1788 and beta-CCE selectively eliminate diazepam-induced feeding in the rabbit.

    PubMed

    Mansbach, R S; Stanley, J A; Barrett, J E

    1984-05-01

    Food intake was monitored in three female and one male adult rabbits following the administration of three drugs known to result in feeding increases in other species. The drugs, diazepam (1.0 mg/kg), cyproheptadine (0.03 mg/kg) and chlorpromazine (1.0 mg/kg) all produced large increases in food intake; of these, only the effect of diazepam, a benzodiazepine, was reversed by doses of the benzodiazepine antagonists Ro 15-1788 (0.3 mg/kg) and Ethyl beta-carboxylate (beta-CCE) (1.0 mg/kg) which, when given alone, did not affect feeding. The results support evidence suggesting that Ro 15-1788 and beta-CCE are specific antagonists of the benzodiazepine receptor and of their effects on a wide range of behaviors.

  3. The effects of putative anxiogenic compounds (FG 7142, CGS 8216 and Ro 15-1788) on the rat corticosterone response.

    PubMed

    Pellow, S; File, S E

    1985-10-01

    The effects of FG 7142, CGS 8216 and Ro 15-1788, three compounds that are believed to produce anxiety by an action at benzodiazepine receptors in the CNS, are investigated on the plasma corticosterone concentrations in the rat both in the home cage and after exposure to novelty stress. FG 7142 (5 mg/kg) and CGS 8216 (10 mg/kg), but not Ro 15-1788 (4 or 10 mg/kg) increased basal corticosterone levels in the home cage, and all three compounds potentiated the increase in corticosterone concentrations observed after exposure to a novel environment. The relationship between the effects of drugs on corticosterone concentrations and on anxiety is considered in the light of these results.

  4. Gigabit close-proximity wireless connections supported by 60 GHz RoF links with low carrier suppression.

    PubMed

    Lebedev, Alexander; Pang, Xiaodan; Olmos, J J Vegas; Forchhammer, Søren; Monroy, Idelfonso Tafur

    2013-10-21

    We present an experimental investigation of the 60 GHz optical carrier suppressed radio over fiber systems with less than 5 dB carrier suppression. As a case study, the 60 GHz RoF signal is generated using a 12.5 Gb/s commercially available Mach-Zehnder modulator biased at its minimum point. We report on error free transmission over 20 km of standard single mode fiber and 1 m of wireless distance. Furthermore, the efficiency of photonic RF generation depending on the value of carrier suppression is reported. We argue that transport of RoF signals with low carrier suppression assisted with simplified techniques of lightwave generation, baseband data modulation, and RF downconversion might be a promising enabling technology for fiber support of close-proximity wireless terminals.

  5. A proposed new diagnostic for Herbig disc geometry. FWHM versus J of CO ro-vibrational lines

    NASA Astrophysics Data System (ADS)

    Hein Bertelsen, R. P.; Kamp, I.; van der Plas, G.; van den Ancker, M. E.; Waters, L. B. F. M.; Thi, W.-F.; Woitke, P.

    2016-05-01

    Aims: The CO ro-vibrational lines observed from Herbig group II discs are often seen to be broad, while the same lines observed from group I discs are often narrow. This difference is not well understood. In this paper we explore the underlying cause for this difference and provide a pathway for a better understanding of the geometry and structure of the inner discs around Herbig Ae/Be stars. Methods: High spectral resolution infrared spectra of CO ro-vibrational emission from six Herbig Ae/Be candidate stars were taken with the CRyogenic high-resolution InfraRed Echelle Spectrograph (CRIRES) at the Very Large Telescope (VLT). From these spectra, we produce individual and co-added CO ro-vibrational line profiles. We investigate line profile shape differences, and we explore the full width at half maximum (FWHM) variations with J quantum number in the context of disc geometry. Furthermore, we put our new sources into the context of earlier observed sources to study a large sample. For comparison, we also investigate the FWHM variations with J of modelled CO ro-vibrational lines from two typical disc geometries produced with the thermochemical disc modelling code ProDiMo. Results: For our new observations of CO ro-vibrational lines, we find that the FWHM of individual lines are in the range of 10-60 km s-1. We find both narrow and broad single-peaked emission lines, but only Hen 2-80 displays double-peaked emission lines. For HD 250550, the FWHM of the CO lines increases with J value, indicating a radially extended emitting region, while Hen 2-80 shows a constant FWHM versus J behaviour, indicating a narrow emitting region. This qualitatively agrees with the two different modelled disc geometries. Comparing dust and gas inner disc geometries (inferred by the spectral energy distribution (SED) and CO ro-vibrational emission) for the expanded sample of observed Herbig discs, we find no clear correspondence between the SED (spectral energy distribution) groups of the

  6. VizieR Online Data Catalog: GTC transit light curves of CoRoT-29b (Palle+, 2016)

    NASA Astrophysics Data System (ADS)

    Palle, E.; Chen, G.; Alonso, R.; Nowak, G.; Deeg, H.; Cabrera, J.; Murgas, F.; Parviainen, H.; Nortmann, L.; Hoyer, S.; Prieto-Arranz, J.; Nespral, D.; Cabrera Lavers, A.; Iro, N.

    2016-04-01

    2 transit light curves of the hot Jupiter CoRoT-29b obtained on the nights of 2014/7/31 and 2015/7/8 using the OSIRIS instrument at the 10.4-m GTC telescope. The light curves have been integrated over the bandpass of 515-915nm, where the wavelength range of 755-765 nm has been excluded due to presence of strong telluric O2 absorption. (2 data files).

  7. Alterations in in-vivo benzodiazepine-receptor binding of C-11-Ro15-1788 (flumazepil)

    SciTech Connect

    Yamasaki, T.; Inoue, O.; Shinoto, H.; Ito, T.; Hashimoto, K.; Suzuki, K.; Tateno, Y.

    1985-05-01

    Alterations of the central benzodiazepine - receptor function caused by the change of physiological or psychological conditions, were recognized in both animal and human studies. Before the human study, animal experiments using tritiated Ro15-1788 were carried out. The stress was produced by forcing the mice to swim in a water-basin at 16/sup 0/C for 5 min. Within 3 min after the forced swimming, the tracer was injected. Brain radioactivities in stress-loaded mice increased over a period of 15 min after the intra-venous injection of tracers, while brain activities of carrier-added tracer decreased. In human study, approximately 5 mCi of C-11-Ro15-1788, which specific activity is 0.3-1.0 Ci/..mu..mol, were intravenously injected to each case. Measurements of the brain activity were performed using positron-CT, with blood sample collection. 31 human studies were performed on. Cerebral cortex time activity curves in several volunteers in nervous and stressful state, showed the same pattern to that in the stress-loaded animal experiment. It is important that the significant different time course of cerebral activity after the injection of labelled Ro15-1788, was observed in stressful state, compared with control, in both human and animal study. From these results, it will be concluded the positron CT study using /sup 11/C-Ro15-1788 will become a new technic to detect the change of psychological conditions in human brain and to diagnose some kind of neuropsychiatric disease.

  8. Dynamic Young Stars and their Disks: A Temporal View of NGC 2264 with Spitzer and CoRoT

    NASA Astrophysics Data System (ADS)

    Cody, Ann Marie; Stauffer, John; Bouvier, Jèrôme

    2014-01-01

    Variability is a signature feature of young stars. Among the well known light curve phenomena are periodic variations attributed to surface spots and irregular changes associated with accretion or circumstellar disk material. While decades of photometric monitoring have provided a framework for classifying young star variability, we still know surprisingly little about its underlying mechanisms and connections to the surrounding disks. In the past few years, dedicated photometric monitoring campaigns from the ground and space have revolutionized our view of young stars in the time domain. We present a selection of optical and infrared time series from several recent campaigns, highlighting the Coordinated Synoptic Investigation of NGC 2264 ("CSI 2264")- a joint30-day effort with the Spitzer, CoRoT, and MOST telescopes. The extraordinary photometric precision, high cadence, and long time baseline of these observations is now enabling correlation of variability properties at very different wavelengths, corresponding to locations from the stellar surface to the inner 0.1 AU of the disk. We present some results of the CSI 2264 program, including new classes of optical/infrared behavior. Further efforts to tie observed variability features to physical models will provide insights into the inner disk environment at a time when planet formation may be underway. Based on data from the Spitzer and CoRoT missions. The CoRoT space mission was developed and is operated by the French space agency CNES, with participation of ESA-s RSSD and Science Programmes, Austria, Belgium, Brazil, Germany, and Spain.

  9. Atrioventricular Conduction Delay in Fetuses Exposed to Anti-SSA/Ro and Anti-SSB/La Antibodies: A Magnetocardiography Study

    PubMed Central

    Wacker-Gußmann, Annette; Paulsen, Henrike; Kiefer-Schmidt, Isabelle; Henes, Joerg; Muenssinger, Jana; Weiss, Magdalene; Goelz, Rangmar; Preissl, Hubert

    2012-01-01

    Background. The presence of anti-SSA/Ro and anti-SSB/La antibodies during pregnancy is associated with fetal congenital heart block (CHB), which is primarily diagnosed through fetal echocardiography. Conclusive information about the complete electrophysiology of the fetal cardiac conducting system is still lacking. In addition to echocardiography, fetal magnetocardiography (fMCG) can be used. fMCG is the magnetic analogue of the fetal electrocardiogram (ECG). Patients and Methods. Forty-eight pregnant women were enrolled in an observational study; 16 of them tested positive for anti-SSA/Ro and anti-SSB/La antibodies. In addition to routine fetal echocardiography, fMCG was used. Fetal cardiac time intervals (fCTIs) were extracted from the magnetic recordings by predefined procedures. ECGs in the neonates of the study group were performed within the first month after delivery. Results. The PQ segment of the fCTI was significantly prolonged in the study group (P = 0.007), representing a delay of the electrical impulse in the atrioventricular (AV) node. Other fCTIs were within normal range. None of the anti-SSA/Ro and/or anti-SSB/La fetuses progressed to a more advanced heart block during pregnancy or after birth. Conclusion. The study identified a low-risk population within antibody positive mothers, where PQ segment prolongation is associated with a lack of progression of the disease. PMID:23320018

  10. CD45RA and CD45RO isoforms in infected malnourished and infected well-nourished children

    PubMed Central

    Nájera, O; González, C; Toledo, G; López, L; Cortés, E; Betancourt, M; Ortiz, R

    2001-01-01

    The aim of this study was to determine if the distribution in vivo of CD4+CD45RA+/CD45RO− (naive), CD4+CD45RA+/CD45RO+ (Ddull) and CD4+CD45RO+ (memory) lymphocytes differs in malnourished infected and well-nourished infected children. The expression of CD45RA (naive) and CD45RO (memory) antigens on CD4+ lymphocytes was analysed by flow cytometry in a prospectively followed cohort of 15 malnourished infected, 12 well-nourished infected and 10 well-nourished uninfected children. Malnourished infected children showed higher fractions of Ddull cells (11·4 ± 0·7%) and lower fractions of memory cells (20·3 ± 1·7%) than the well-nourished infected group (8·8 ± 0·8 and 28·1 ± 1·8%, respectively). Well-nourished infected children showed increased percentages of memory cells, an expected response to infection. Impairment of the transition switch to the CD45 isoforms in malnourished children may explain these findings, and may be one of the mechanisms involved in immunodeficiency in these children. PMID:11737063

  11. Future Energy Benchmark for Desalination: is it Better to have a Power (electricity) Plant with ro or Med/msf?

    NASA Astrophysics Data System (ADS)

    Shahzad, Muhammad Wakil; Ng, Kim Choon; Thu, Kyaw

    2016-06-01

    Power and desalination cogeneration plants are common in many water scared courtiers. Designers and planners for cogeneration face tough challenges in deciding the options:- Is it better to operate a power plant (PP) with the reverse osmosis (i.e., PP+RO) or the thermally-driven multi-effect distillation/multi-stage flashed (PP+MED/MSF) methods. From literature, the RO methods are known to be energy efficient whilst the MED/MSF are known to have excellent thermodynamic synergies as only low pressure and temperature steam are used. Not with-standing the challenges of severe feed seawater of the Gulf, such as the frequent harmful algae blooms (HABs) and high silt contents, this presentation presents a quantitative analyses using the exergy and energetic approaches in evaluating the performances of a real cogeneration plant that was recently proposed in the eastern part of Saudi Arabia. We demonstrate that the process choice of PP+RO versus PP+MED depends on the inherent efficiencies of individual process method which is closely related to innovative process design. In this connection, a method of primary fuel cost apportionment for a co-generation plant with a MED desalination is presented. We show that an energy approach, that captures the quality of expanding steam, is a better method over the conventional work output (energetic) and the energy method seems to be over-penalizing a thermally-driven MED by as much as 22% in the operating cost of water.

  12. Simultaneous generation of wavelength division multiplexing PON and RoF signals using a hybrid mode-locked laser

    NASA Astrophysics Data System (ADS)

    Aldaya, Ivan; Campuzano, Gabriel; Castañón, Gerardo

    2015-06-01

    The use of millimeter-wave (mm-wave) frequencies has been proposed to overcome the imminent saturation of the ultra high frequency band, justifying research on radio over fiber (RoF) networks as an inexpensive and green solution to distribute multi-Gbps signals. Coincidently, telecommunication operators are investing a significant effort to deploy their passive optical network (PON) infrastructure closer to the users. In this work, we present a novel cost-efficient architecture based on a hybrid mode locked laser capable to simultaneously generate up-to 5 wavelength division multiplexing PON and RoF channels, being compatible with the 50-GHz ITU frequency grid. We analyze the limits of operation of our proposed architecture considering the high modal relative intensity noise induced by mode partition noise, as well as fiber impairments, such as chromatic dispersion and nonlinearities. The feasibility of generation and transmission of 5×10-Gbps PON and 5×5-Gbps RoF using orthogonal frequency division multiplexing up to 50 km has been demonstrated through realistic numerical simulations.

  13. A quasi-classical trajectory study of the OH + SO reaction: the role of ro-vibrational energy.

    PubMed

    Pires, W A D; Garrido, J D; Nascimento, M A C; Ballester, M Y

    2014-07-07

    A study of the OH + SO → H + SO2 reaction using a quasi-classical trajectory method is presented with the aim of investigating the role of the ro-vibrational energy of the reactants in the reactivity. The calculations were carried out using a previously reported global potential energy surface for HSO2((2)A). Different initial conditions with one and both reactants ro-vibrationally excited were studied. The reactive cross sections, for each studied combination, are calculated and then fitted to a capture-like model combined with a factor accounting for the recrossing effects. The Vibrational Energy Quantum Mechanical Threshold of the Complex method was used to correct for the zero-point vibrational energy leakage of the classical calculations. State specific and averaged rate constants are reported. The reactivity is affected when ro-vibrational energy of either of the reactants is changed. The present calculations provide a theoretical support for the experimental rate constant for temperatures below 550 K, but fail to account for the significant fall in the observed rate constant upon increasing the temperature above this value.

  14. Benzodiazepine recognition site inverse agonists Ro-15-4513 and FG 7142 both antagonize the EEG effects of ethanol in the rat

    SciTech Connect

    Marrosu, F.; Mereu, G.; Giorgi, O.; Corda, M.G.

    1988-01-01

    The aim of the present study was to compare the ability of Ro 15-4513 and FG 7142, two inverse agonists for benzodiazepine recognition sites, to antagonize the EEG effects of ethanol in freely moving rats. Ethanol induced sedation and ataxia associated with a progressive suppression of the fast cortical activities and an enhancement of low frequencies in both cortical and hippocampal tracings. In contrast, Ro 15-4513 and FG 7142 both caused a state of alertness associated with desynchronized cortical activity and theta hippocampal rhythm as well as spiking activity which was predominantly observed in the cortical tracings. When rats were treated with FG 7142 or Ro 15-4513 either before or after ethanol, a reciprocal antagonism of the behavioral and EEG effects of ethanol and of the partial inverse agonists was observed. These data support the view that the anti-ethanol effects of Ro 15-4513 may be related to its partial inverse agonist properties.

  15. Development of roGFP2-derived redox probes for measurement of the glutathione redox potential in the cytosol of severely glutathione-deficient rml1 seedlings

    PubMed Central

    Aller, Isabel; Rouhier, Nicolas; Meyer, Andreas J.

    2013-01-01

    Glutathione is important for detoxification, as a cofactor in biochemical reactions and as a thiol-redox buffer. The cytosolic glutathione buffer is normally highly reduced with glutathione redox potentials (EGSH) of more negative than −310 mV. Maintenance of such negative redox potential is achieved through continuous reduction of glutathione disulfide by glutathione reductase (GR). Deviations from steady state glutathione redox homeostasis have been discussed as a possible mean to alter the activity of redox-sensitive proteins through switching of critical thiol residues. To better understand such signaling mechanisms it is essential to be able to measure EGSH over a wide range from highly negative redox potentials down to potentials found in mutants that show already severe phenotypes. With the advent of redox-sensitive GFPs (roGFPs), understanding the in vivo dynamics of the thiol-based redox buffer system became within reach. The original roGFP versions, roGFP1 and roGFP2, however, have midpoint potentials between −280 and −290 mV rendering them fully oxidized in the ER and almost fully reduced in the cytosol, plastids, mitochondria, and peroxisomes. To extend the range of suitable probes we have engineered a roGFP2 derivative, roGFP2-iL, with a midpoint potential of about −238 mV. This value is within the range of redox potentials reported for homologous roGFP1-iX probes, albeit with different excitation properties. To allow rapid and specific equilibration with the glutathione pool, fusion constructs with human glutaredoxin 1 (GRX1) were generated and characterized in vitro. GRX1-roGFP2-iL proved to be suitable for in vivo redox potential measurements and extends the range of EGSH values that can be measured in vivo with roGFP2-based probes from about −320 mV for GRX1-roGFP2 down to about −210 mV for GRX1-roGFP2-iL. Using both probes in the cytosol of severely glutathione-deficient rml1 seedlings revealed an EGSH of about −260 mV in this mutant

  16. Ro 04-6790-induced cognitive enhancement: No effect in trace conditioning and novel object recognition procedures in adult male Wistar rats

    PubMed Central

    Thur, K.E.; Nelson, A.J.D.; Cassaday, H.J.

    2014-01-01

    The evidence for cognitively enhancing effects of 5-hydroxytryptamine6 (5-HT6) receptor antagonists such as Ro 04-6790 is inconsistent and seems to depend on the behavioral test variant in use. Trace conditioning holds promise as a behavioral assay for hippocampus-dependent working memory function. Accordingly, Experiment 1 assessed the effect of Ro 04-6790 (5 and 10 mg/kg i.p.) on associating a noise conditioned stimulus paired with foot shock (unconditioned stimulus) at a 3 or 30 s trace interval in adult male Wistar rats. Contextual conditioning was measured as suppression to the contextual cues provided by the experimental chambers and as suppression to a temporally extended light background stimulus which provided an experimental context. Experiment 2 assessed the effect of Ro 04-6790 (5 and 10 mg/kg i.p.) on recognition memory as tested by the exploration of novel relative to familiar objects in an open arena. In Experiment 1, Ro 04-6790 (5 and 10 mg/kg) was without effect on trace and contextual conditioning. In Experiment 2, there was no indication of the expected improvement under Ro 04-6790 at the same doses previously found to enhance recognition memory as measured in tests of novel object exploration. Thus, there was no evidence that treatment with the 5-HT6 receptor antagonist Ro 04-6790 acted as a cognitive enhancer in either trace conditioning or object recognition procedures. We cannot exclude the possibility that the experimental procedures used in the present study would have been sensitive to the cognitive enhancing effects of Ro 04-6790 in a different dose range, behavioral test variant, or in a different strain of rat. Nonetheless the drug treatment was not ineffective in that object exploration was reduced under 10 mg/kg Ro 04-6790. PMID:25450117

  17. Tent Preservation Project - Demonstration/Validation for Replacement of Aqueous Copper 8 Quinolinolate Treatment of Cotton Webbing With RO-59-WP

    DTIC Science & Technology

    2008-07-01

    on military tents. This material is subject to degradation in both use and storage by exposure to bacteria and fungi in a moist environment . The...times due to environmental concerns. Tents coated with both the baseline coating (Copper 8 only) and two candidate coatings (RO-59-WP only and RO-59...WP applied over Copper 8) were exposed to three different outdoor environments in the continental United States and were subsequently destructively

  18. Ro 04-6790-induced cognitive enhancement: no effect in trace conditioning and novel object recognition procedures in adult male Wistar rats.

    PubMed

    Thur, K E; Nelson, A J D; Cassaday, H J

    2014-12-01

    The evidence for cognitively enhancing effects of 5-hydroxytryptamine6 (5-HT6) receptor antagonists such as Ro 04-6790 is inconsistent and seems to depend on the behavioral test variant in use. Trace conditioning holds promise as a behavioral assay for hippocampus-dependent working memory function. Accordingly, Experiment 1 assessed the effect of Ro 04-6790 (5 and 10mg/kg i.p.) on associating a noise conditioned stimulus paired with foot shock (unconditioned stimulus) at a 3 or 30s trace interval in adult male Wistar rats. Contextual conditioning was measured as suppression to the contextual cues provided by the experimental chambers and as suppression to a temporally extended light background stimulus which provided an experimental context. Experiment 2 assessed the effect of Ro 04-6790 (5 and 10mg/kg i.p.) on recognition memory as tested by the exploration of novel relative to familiar objects in an open arena. In Experiment 1, Ro 04-6790 (5 and 10mg/kg) was without effect on trace and contextual conditioning. In Experiment 2, there was no indication of the expected improvement under Ro 04-6790 at the same doses previously found to enhance recognition memory as measured in tests of novel object exploration. Thus, there was no evidence that treatment with the 5-HT6 receptor antagonist Ro 04-6790 acted as a cognitive enhancer in either trace conditioning or object recognition procedures. We cannot exclude the possibility that the experimental procedures used in the present study would have been sensitive to the cognitive enhancing effects of Ro 04-6790 in a different dose range, behavioral test variant, or in a different strain of rat. Nonetheless the drug treatment was not ineffective in that object exploration was reduced under 10mg/kg Ro 04-6790.

  19. CD45RO+ Memory T Lymphocytes — a Candidate Marker for TNM-Immunoscore in Squamous Non–Small Cell Lung Cancer1

    PubMed Central

    Paulsen, Erna-Elise; Kilvaer, Thomas; Khanehkenari, Mehrdad Rakaee; Maurseth, Ramona Johansen; Al-Saad, Samer; Hald, Sigurd M.; Al-Shibli, Khalid; Andersen, Sigve; Richardsen, Elin; Busund, Lill-Tove; Bremnes, Roy; Donnem, Tom

    2015-01-01

    Tumor-infiltrating lymphocytes (TILs) are vital in limiting cancer progression and may supplement the TNM classification. CD45RO+ memory TILs show major prognostic impact in various malignancies but have not been extensively explored in non–small cell lung cancer (NSCLC). In this study, we aimed to evaluate their potential in a NSCLC TNM-Immunoscore. Tissue microarrays were constructed from tumor tissue samples from two cohorts including in total 536 patients (University Hospital of North Norway, n = 285; Nordland Hospital, n = 251) with primary resected stage I to IIIA NSCLC. The density of CD45RO+ and CD8+ TILs in tumor epithelial and stromal compartments of the tumors was evaluated by immunohistochemistry. In univariate analyses, intraepithelial CD45RO+ TIL density (T-CD45RO) was a significant prognostic factor for disease-specific survival (P = .007), limited to the squamous cell carcinoma (SCC) histology subgroup (P < .001), where it was significant in both cohorts (University Hospital of North Norway, P = .003; Nordland Hospital, P = .022). Combining T-CD45RO and stromal CD8+ TIL density (S-CD8) increased the prognostic impact in SCC (P < .001) and showed a significant impact within all pathological stages (I, P = .025; II, P < .001; III, P = .001). In the multivariate analysis, T-CD45RO was an independent positive prognostic factor for SCC (hazard ratio 2.65, 95% confidence interval 1.64-4.28, P < .001), and in combination with S-CD8, the prognostic impact increased vastly (high + high versus low + low: hazard ratio 6.50, 95% confidence interval 3.54-11.91, P < .001). In conclusion, T-CD45RO was an independent prognostic factor for SCC NSCLC. When combined with S-CD8, the prognostic impact increased and was significant within each pathological stage. We propose CD45RO as a candidate marker for TNM-Immunoscore in SCC NSCLC. PMID:26678911

  20. SGLT2 inhibitors.

    PubMed

    Dardi, I; Kouvatsos, T; Jabbour, S A

    2016-02-01

    Diabetes mellitus is a serious health issue and an economic burden, rising in epidemic proportions over the last few decades worldwide. Although several treatment options are available, only half of the global diabetic population achieves the recommended or individualized glycemic targets. Sodium-glucose cotransporter 2 (SGLT2) inhibitors are a new class of antidiabetic agents with a novel insulin-independent action. SGLT2 is a transporter found in the proximal renal tubules, responsible for the reabsorption of most of the glucose filtered by the kidney. Inhibition of SGLT2 lowers the blood glucose level by promoting the urinary excretion of excess glucose. Due to their insulin-independent action, SGLT2 inhibitors can be used with any degree of beta-cell dysfunction or insulin resistance, related to a very low risk of hypoglycemia. In addition to improving glycemic control, SGLT2 inhibitors have been associated with a reduction in weight and blood pressure when used as monotherapy or in combination with other antidiabetic agents in patients with type 2 diabetes mellitus (T2DM). Treatment with SGLT2 inhibitors is usually well tolerated; however, they have been associated with an increased incidence of urinary tract and genital infections, although these infections are usually mild and easy to treat. SGLT2 inhibitors are a promising new option in the armamentarium of drugs for patients with T2DM.

  1. [Acquired coagulant factor inhibitors].

    PubMed

    Nogami, Keiji

    2015-02-01

    Acquired coagulation factor inhibitors are an autoimmune disease causing bleeding symptoms due to decreases in the corresponding factor (s) which result from the appearance of autoantibodies against coagulation factors (inhibitor). This disease is quite different from congenital coagulation factor deficiencies based on genetic abnormalities. In recent years, cases with this disease have been increasing, and most have anti-factor VIII autoantibodies. The breakdown of the immune control mechanism is speculated to cause this disease since it is common in the elderly, but the pathology and pathogenesis are presently unclear. We herein describe the pathology and pathogenesis of factor VIII and factor V inhibitors. Characterization of these inhibitors leads to further analysis of the coagulation process and the activation mechanisms of clotting factors. In the future, with the development of new clotting examination method (s), we anticipate that further novel findings will be obtained in this field through inhibitor analysis. In addition, detailed elucidation of the coagulation inhibitory mechanism possibly leading to hemostatic treatment strategies for acquired coagulation factor disorders will be developed.

  2. Identifying the upper atmosphere structure of the inflated hot sub-Neptune CoRoT-24b

    NASA Astrophysics Data System (ADS)

    Juvan, Ines; Lammer, Helmut; Erkaev, Nikolai V.; Fossati, Luca; Cubillos, Patricio E.; Guenther, Eike; Odert, Petra; Kislyakova, Kristina G.; Lendl, Monika

    2016-04-01

    The CoRoT satellite mission discovered two Neptune-type planets, CoRoT-24b and CoRoT-24c, with observed transit radii of ≈3.7REarth and ≈4.9REarth and masses of ≤5.7MEarth and ≈28MEarth, respectively. From the deduced low mean densities it can be expected that their planetary cores are most likely surrounded by H2 dominated envelopes. While having very similar radii, the outer planet CoRoT-24c is at least 4.9 times more massive than its neighbour, indicating that their atmospheres can be fundamentally different. Therefore, we have investigated the upper atmosphere structure and escape rates of these two planets. We applied a hydrodynamic upper atmosphere model including heating by absorption of stellar extreme ultraviolet and X-ray (XUV) radiation, under the assumption that the observed transit radius RT is produced by Rayleigh scattering and H2-H2 collision absorption in a pure hydrogen atmosphere. This corresponds to a pressure level near 1 bar. We find an unsustainably high hydrodynamic escape rate of 1.6 × 1011 g/s for the atmosphere of CoRoT-24b. If real, such high atmospheric escape would lead to substantial mass loss from the planetary atmosphere, shrinking it to ≈2.2REarth within ≈4 Myr, which is inconsistent with the old age of the system. The solution to this discrepancy is that the observed transit radius RT must be 30-60% larger than the actual planetary radius at the 1 bar pressure level. We suggest that the observed transit radius RT is produced by absorption through scattering processes due to high altitude clouds or hazes. The Kepler satellite has discovered similar close-in low-density Neptune-type planets. We propose that it is very likely that the observed transit radii for the vast majority of these planets also differ from their actual planetary radii at the 1 bar pressure level. This would introduce a systematic bias in the measured radii and has dramatic implications in the determination of the mass-radius relation and for planet

  3. In vivo binding of (/sup 3/H)Ro 15-1788 in mice: comparison with the in vivo binding of (/sup 3/H)flunitrazepam

    SciTech Connect

    Potier, M.C.; de Carvalho, L.P.; Dodd, R.H.; Brown, C.L.; Rossier, J.

    1988-01-01

    Benzodiazepine binding sites have generally been labelled with benzodiazepine agonists: (/sup 3/H)flunitrazepam and (/sup 3/H)diazepam in vivo. The authors studied the in vivo binding of the antagonist (/sup 3/H)Ro 15-1788 in mice and compared it to the in vivo binding of (/sup 3/H)flunitrazepam. For this in vivo labelling, mice were injected with labelled and unlabelled ligands. Animals were then sacrificed and bound radioactivity was measured after homogenization of the excised brain and filtration of the homogenate. (/sup 3/H)Ro 15-1788 is a better tool than (/sup 3/H)flunitrazepam for in vivo labelling of benzodiazepine receptors since 1) it labels specifically the central type binding sites, 2) injection of 4 times less (/sup 3/H)Ro 15-1788 than (/sup 3/H)flunitrazepam produced the same amount of bound radioactivity, 3) 70-90% of the total (/sup 3/H)Ro 15-1788 present in the brain is membrane bound instead of 45-55% with (/sup 3/H)flunitrazepam, 4) maximal binding of (/sup 3/H)Ro 15-1788 is reached within 3 min, 5) only 5% of the membrane bound (/sup 3/H)Ro 15-1788 is nonspecific instead of 15% for (/sup 3/H)flunitrazepam.

  4. Changes in mouse hippocampal EEG characteristics after oral administration of Ro 41-3696, nitrazepam, or zopiclone alone and in combination with ethanol.

    PubMed

    Tsuboi, M; Tanaka, Y; Himori, N

    1994-11-01

    Ro 41-3696, a benzoquinolizinone derivative, is a partial agonist to the benzodiazepine (BDZ) receptor and is expected to be a nonsedative hypnotic. The present comparative study was performed to examine the effects of the oral administration of Ro 41-3696, nitrazepam or zopiclone alone and in combination with a 'social' dose of ethanol on mouse hippocampal EEG. Ro 41-3696 (1-10 mg/kg), nitrazepam (0.1 and 1 mg/kg), and zopiclone (1 and 10 mg/kg) each alone caused an increase in the drowsy EEG pattern associated with a decrease in the duration of hippocampal rhythmic slow-wave activity (RSA). On the other hand, nitrazepam markedly lowered, while Ro 41-3696 and zopiclone slightly lowered the RSA frequency during waking mobility. In combination with a noneffective oral dose (1 g/kg) of ethanol, the reductions in both total duration and peak frequency of RSA caused by nitrazepam, unlike those by Ro 41-3696 and zopiclone, were significantly potentiated. In addition, only nitrazepam produced motor impairment. These results suggest that Ro 41-3696 acts more selectively than nitrazepam to promote the drowsy EEG pattern, and the partial agonistic properties may minimize the residual effects during waking mobility similar to the short-acting agent zopiclone.

  5. GPS RO sensing of Boundary Layer Height within Southern Ocean Cyclones

    NASA Astrophysics Data System (ADS)

    Schuddeboom, Alex; McDonald, Adrian; Katurji, Marwan; Morgenstern, Olaf; Harvey, Mike

    2016-04-01

    The COSMIC constellation of GPS RO satellites has been used extensively over the previous few years to generate climatologies of boundary layer height (BLH). These satellites use high precision clocks to measure the time it takes for a signal to be transmitted through the atmosphere. From the time measurements, the angle of refraction of the signal can be calculated and then used in turn to calculate atmospheric refractivity. Boundary layer heights can then be determined by identifying sharp gradients in the refractivity profile. The results of this approach have been compared with radiosonde data and show a high level of agreement. By using this technique, we also generated a BLH climatology which was then used to analyse how the height of the boundary layer varies within the specific meteorological context of Southern Ocean cyclones. Analysis of the BLH behaviour over cyclones was primarily based upon generating cyclone composites. This is done by averaging together measurements in a cyclone relative framework to generate a representative cyclone. This technique allows a direct examination of the mean state, however it is also valuable for further analysis such as splitting the composite into regions and analysing the distribution of values over each of these sub-regions. We also investigated the relationship between boundary layer height and surface variables. There is a particularly strong negative relationship between sea ice concentration and boundary layer height. The reasons for this phenomenon are not entirely clear but appear to be at least partially related to changes in the surface sensible heat flux. The effects of other surface variables such as air temperature, sea surface temperature and wind speeds were relatively minor.

  6. On the Lowest Ro-Vibrational States of Protonated Methane: Experiment and Analytical Model

    NASA Astrophysics Data System (ADS)

    Schmiedt, Hanno; Jensen, Per; Asvany, Oskar; Schlemmer, Stephan

    2016-06-01

    Protonated methane, CH_5^+, is the prototype of an extremely floppy molecule. To the best of our knowledge all barriers are surmountable in the rovibrational ground state; the large amount of zero-point vibrational energy leads to large amplitude motions for many degrees of freedom. Low resolution but broad band vibrational spectroscopy [1] revealed an extremely wide range of C-H stretching vibrations. Comparison with theoretical IR spectra supported the structural motif of a CH_3 tripod and an H_2 moiety, bound to the central carbon atom by a 3c2e bond. In a more dynamic picture the five protons surround the central carbon atom without significant restrictions on the H-C-H bending or H_n-C torsional motions. The large-amplitude internal motions preclude a simple theoretical description of the type possible for more conventional molecules, such as the related spherical-top methane molecule. Recent high-resolution ro-vibrational spectra obtained in cold ion trap experiments [2] show that the observed CH_5^+ transitions belong to a very well-defined energy level scheme describing the lowest rotational and vibrational states of this enigmatic molecule. Here we analyse the experimental ground state combination differences and associate them with the motional states of CH_5^+ allowed by Fermi-Dirac statistics. A model Hamiltonian for unrestricted internal rotations in CH_5^+ yields a simple analytical expression for the energy eigenvalues, expressed in terms of new quantum numbers describing the free internal rotation. These results are compared to the experimental combination differences and the validity of the model will be discussed together with the underlying assumptions. [1] O. Asvany, P. Kumar, I. Hegemann, B. Redlich, S. Schlemmer and D. Marx, Science 309, (2005) 1219-1222 [2] O. Asvany, K.M.T. Yamada, S. Brünken, A. Potapov, S. Schlemmer, Science 347 (2015) 1346-1349

  7. ON THE ASYMMETRY OF THE OH RO-VIBRATIONAL LINES IN HD 100546

    SciTech Connect

    Fedele, D.; Bruderer, S.; Van den Ancker, M. E.; Pascucci, I. E-mail: mvandena@eso.org

    2015-02-10

    We present multi-epoch high-spectral resolution observations with VLT/CRIRES of the OH doublet {sup 2}Π{sub 3/2} P4.5 (1+, 1–) (2.934 μm) toward the protoplanetary disk around HD 100546. The OH doublet is detected at all epochs and is spectrally resolved while nearby H{sub 2}O lines remain undetected. The OH line velocity profile is different in the three data sets: in the first epoch (2012 April, P.A. = 26°) the OH lines are symmetric and line broadening is consistent with the gas being in Keplerian rotation around the star. No OH emission is detected within a radius of 8-11 AU from the star: the line emitting region is similar in size and extent to that of the CO ro-vibrational lines. In the other two epochs (2013 March and 2014 April, P.A. = 90° and 10°, respectively) the OH lines appear asymmetric and fainter compared to 2012 April. We investigate the origin of these line asymmetries which were taken by previous authors as evidence for tidal interaction between a (unseen) massive planet and the disk. We show that the observed asymmetries can be fully explained by a misalignment of the slit of the order of 0.''04-0.''20 with respect to the stellar position. The disk is spatially resolved and the slit misalignment is likely caused by the extended dust emission which is brighter than the stellar photosphere at near-infrared wavelengths which is the wavelength used for the pointing. This can cause the photo-center of HD 100546 to be misaligned with the stellar position at near-infrared wavelengths.

  8. Atmospheric parameters and chemical properties of red giants in the CoRoT asteroseismology fields

    NASA Astrophysics Data System (ADS)

    Morel, T.; Miglio, A.; Lagarde, N.; Montalbán, J.; Rainer, M.; Poretti, E.; Eggenberger, P.; Hekker, S.; Kallinger, T.; Mosser, B.; Valentini, M.; Carrier, F.; Hareter, M.; Mantegazza, L.

    2014-04-01

    A precise characterisation of the red giants in the seismology fields of the CoRoT satellite is a prerequisite for further in-depth seismic modelling. High-resolution FEROS and HARPS spectra were obtained as part of the ground-based follow-up campaigns for 19 targets holding great asteroseismic potential. These data are used to accurately estimate their fundamental parameters and the abundances of 16 chemical species in a self-consistent manner. Some powerful probes of mixing are investigated (the Li and CNO abundances, as well as the carbon isotopic ratio in a few cases). The information provided by the spectroscopic and seismic data is combined to provide more accurate physical parameters and abundances. The stars in our sample follow the general abundance trends as a function of the metallicity observed in stars of the Galactic disk. After an allowance is made for the chemical evolution of the interstellar medium, the observational signature of internal mixing phenomena is revealed through the detection at the stellar surface of the products of the CN cycle. A contamination by NeNa-cycled material in the most massive stars is also discussed. With the asteroseismic constraints, these data will pave the way for a detailed theoretical investigation of the physical processes responsible for the transport of chemical elements in evolved, low- and intermediate-mass stars. Based on observations collected at La Silla Observatory, ESO (Chile) with the FEROS and HARPS spectrograph at the 2.2 and 3.6-m telescopes under programs LP178.D-0361, LP182.D-0356, and LP185.D-0056.Appendix A is available in electronic form at http://www.aanda.orgTables A.2 to A.6 are available at the CDS via anonymous ftp to http://cdsarc.u-strasbg.fr (ftp://130.79.128.5) or via http://cdsarc.u-strasbg.fr/viz-bin/qcat?J/A+A/564/A119

  9. In vitro and in vivo antibacterial activities of CS-023 (RO4908463), a novel parenteral carbapenem.

    PubMed

    Koga, Tetsufumi; Abe, Tomomi; Inoue, Harumi; Takenouchi, Takashi; Kitayama, Akiko; Yoshida, Tatsuhiko; Masuda, Nobuhisa; Sugihara, Chika; Kakuta, Masayo; Nakagawa, Miyuki; Shibayama, Takahiro; Matsushita, Yoko; Hirota, Takashi; Ohya, Satoshi; Utsui, Yukio; Fukuoka, Takashi; Kuwahara, Syogo

    2005-08-01

    CS-023 (RO4908463, formerly R-115685) is a novel 1beta-methylcarbapenem with 5-substituted pyrrolidin-3-ylthio groups, including an amidine moiety at the C-2 position. Its antibacterial activity was tested against 1,214 clinical isolates of 32 species and was compared with those of imipenem, meropenem, ceftazidime, ceftriaxone, ampicillin, amikacin, and levofloxacin. CS-023 exhibited a broad spectrum of activity against gram-positive and -negative aerobes and anaerobes, including methicillin-resistant Staphylococcus aureus (MRSA), methicillin-resistant Staphylococcus epidermidis, penicillin-resistant Streptococcus pneumoniae (PRSP), beta-lactamase-negative ampicillin-resistant Haemophilus influenzae, and Pseudomonas aeruginosa. CS-023 showed the most potent activity among the compounds tested against P. aeruginosa and MRSA, with MICs at which 90% of isolates tested were inhibited of 4 microg/ml and 8 microg/ml, respectively. CS-023 was stable against hydrolysis by the beta-lactamases from Enterobacter cloacae and Proteus vulgaris. CS-023 also showed potent activity against extended-spectrum beta-lactamase-producing Escherichia coli. The in vivo efficacy of CS-023 was evaluated with a murine systemic infection model induced by 13 strains of gram-positive and -negative pathogens and a lung infection model induced by 2 strains of PRSP (serotypes 6 and 19). Against the systemic infections with PRSP, MRSA, and P. aeruginosa and the lung infections, the efficacy of CS-023 was comparable to those of imipenem/cilastatin and vancomycin (tested against lung infections only) and superior to those of meropenem, ceftriaxone, and ceftazidime (tested against P. aeruginosa infections only). These results suggest that CS-023 has potential for the treatment of nosocomial bacterial infections by gram-positive and -negative pathogens, including MRSA and P. aeruginosa.

  10. SPITZER INFRARED OBSERVATIONS AND INDEPENDENT VALIDATION OF THE TRANSITING SUPER-EARTH CoRoT-7 b

    SciTech Connect

    Fressin, Francois; Torres, Guillermo; Charbonneau, David; Pont, Frederic; Knutson, Heather A.; Mazeh, Tsevi; Aigrain, Suzanne; Fridlund, Malcolm; Guillot, Tristan; Rauer, Heike

    2012-01-20

    The detection and characterization of the first transiting super-Earth, CoRoT-7 b, has required an unprecedented effort in terms of telescope time and analysis. Although the star does display a radial-velocity signal at the period of the planet, this has been difficult to disentangle from the intrinsic stellar variability and pinning down the velocity amplitude has been very challenging. As a result, the precise value of the mass of the planet-and even the extent to which it can be considered to be confirmed-has been debated in the recent literature, with six mass measurements published so far based on the same spectroscopic observations, ranging from about 2 to 8 Earth masses. Here we report on an independent validation of the planet discovery using one of the fundamental properties of a transit signal: its achromaticity. We observed four transits of CoRoT-7 b at 4.5 {mu}m and 8.0 {mu}m with the Infrared Array Camera (IRAC) on board the Spitzer Space Telescope in order to determine whether the depth of the transit signal in the near-infrared is consistent with that observed in the CoRoT bandpass, as expected for a planet. We detected the transit and found an average depth of 0.426 {+-} 0.115 mmag at 4.5 {mu}m, which is in good agreement with the depth of 0.350 {+-} 0.011 mmag (ignoring limb darkening) found by CoRoT. The observations at 8.0 {mu}m did not yield a significant detection. The 4.5 {mu}m observations place important constraints on the kinds of astrophysical false positives that could mimic the signal. Combining this with additional constraints reported earlier, we performed an exhaustive exploration of possible blend scenarios for CoRoT-7 b using the BLENDER technique. We are able to rule out the vast majority of false positives, and the remaining ones are found to be much less likely than a true transiting planet. We thus validate CoRoT-7 b as a bona fide planet with a very high degree of confidence, independently of any radial-velocity information

  11. Spitzer Infrared Observations and Independent Validation of the Transiting Super-Earth CoRoT-7 b

    NASA Astrophysics Data System (ADS)

    Fressin, Francois; Torres, Guillermo; Pont, Frederic; Knutson, Heather A.; Charbonneau, David; Mazeh, Tsevi; Aigrain, Suzanne; Fridlund, Malcolm; Henze, Christopher E.; Guillot, Tristan; Rauer, Heike

    2012-01-01

    The detection and characterization of the first transiting super-Earth, CoRoT-7 b, has required an unprecedented effort in terms of telescope time and analysis. Although the star does display a radial-velocity signal at the period of the planet, this has been difficult to disentangle from the intrinsic stellar variability and pinning down the velocity amplitude has been very challenging. As a result, the precise value of the mass of the planet—and even the extent to which it can be considered to be confirmed—has been debated in the recent literature, with six mass measurements published so far based on the same spectroscopic observations, ranging from about 2 to 8 Earth masses. Here we report on an independent validation of the planet discovery using one of the fundamental properties of a transit signal: its achromaticity. We observed four transits of CoRoT-7 b at 4.5 μm and 8.0 μm with the Infrared Array Camera (IRAC) on board the Spitzer Space Telescope in order to determine whether the depth of the transit signal in the near-infrared is consistent with that observed in the CoRoT bandpass, as expected for a planet. We detected the transit and found an average depth of 0.426 ± 0.115 mmag at 4.5 μm, which is in good agreement with the depth of 0.350 ± 0.011 mmag (ignoring limb darkening) found by CoRoT. The observations at 8.0 μm did not yield a significant detection. The 4.5 μm observations place important constraints on the kinds of astrophysical false positives that could mimic the signal. Combining this with additional constraints reported earlier, we performed an exhaustive exploration of possible blend scenarios for CoRoT-7 b using the BLENDER technique. We are able to rule out the vast majority of false positives, and the remaining ones are found to be much less likely than a true transiting planet. We thus validate CoRoT-7 b as a bona fide planet with a very high degree of confidence, independently of any radial-velocity information. Our Spitzer

  12. Cholinesterase inhibitors from botanicals

    PubMed Central

    Ahmed, Faiyaz; Ghalib, Raza Murad; Sasikala, P.; Ahmed, K. K. Mueen

    2013-01-01

    Alzheimer's disease (AD) is a progressive neurodegenerative disease, wherein a progressive loss of cholinergic synapses occurs in hippocampus and neocortex. Decreased concentration of the neurotransmitter, acetylcholine (ACh), appears to be critical element in the development of dementia, and the most appropriate therapeutic approach to treat AD and other form of dementia is to restore acetylcholine levels by inhibiting both major form of cholinesterase: Acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). Consequently, researches have focused their attention towards finding cholinesterase inhibitors from natural products. A large number of such inhibitors have been isolated from medicinal plants. This review presents a comprehensive account of the advances in field of cholinesterase inhibitor phytoconstituents. The structures of some important phytoconstituents (collected through www.Chemspider.com) are also presented and the scope for future research is discussed. PMID:24347920

  13. Combined Treatment with a BACE Inhibitor and Anti-Aβ Antibody Gantenerumab Enhances Amyloid Reduction in APPLondon Mice

    PubMed Central

    Ozmen, Laurence; Caruso, Antonello; Narquizian, Robert; Hilpert, Hans; Jacobsen, Bjoern; Terwel, Dick; Tanghe, An

    2014-01-01

    Therapeutic approaches for prevention or reduction of amyloidosis are currently a main objective in basic and clinical research on Alzheimer‘s disease. Among the agents explored in clinical trials are anti-Aβ peptide antibodies and secretase inhibitors. Most anti-Aβ antibodies are considered to act via inhibition of amyloidosis and enhanced clearance of existing amyloid, although secretase inhibitors reduce the de novo production of Aβ. Limited information is currently available on the efficacy and potential advantages of combinatorial antiamyloid treatment. We performed a chronic study in APPLondon transgenic mice that received treatment with anti-Aβ antibody gantenerumab and BACE inhibitor RO5508887, either as mono- or combination treatment. Treatment aimed to evaluate efficacy on amyloid progression, similar to preexisting amyloidosis as present in Alzheimer's disease patients. Mono-treatments with either compound caused a dose-dependent reduction of total brain Aβ and amyloid burden. Combination treatment with both compounds significantly enhanced the antiamyloid effect. The observed combination effect was most pronounced for lowering of amyloid plaque load and plaque number, which suggests effective inhibition of de novo plaque formation. Moreover, significantly enhanced clearance of pre-existing amyloid plaques was observed when gantenerumab was coadministered with RO5508887. BACE inhibition led to a significant time- and dose-dependent decrease in CSF Aβ, which was not observed for gantenerumab treatment. Our results demonstrate that combining these two antiamyloid agents enhances overall efficacy and suggests that combination treatments may be of clinical relevance. PMID:25164658

  14. Thrombin inhibitor design.

    PubMed

    Sanderson, P E; Naylor-Olsen, A M

    1998-08-01

    Recently, iv formulated direct thrombin inhibitors have been shown to be safe and efficacious alternatives to heparin. These results have fueled the hopes for an orally active compound. Such a compound could be a significant advance over warfarin if it had predictable pharmacokinetics and a duration of action sufficient for once or twice a day dosing. In order to develop an orally active compound which meets these criteria, the deficiencies of the prototype inhibitor efegatran have had to be addressed. First, using a combination of structure based design and empirical structure optimization, more selective compounds have been identified by modifying the P1 group or by incorporating different peptidomimetic P2/P3 scaffolds. Secondly, this optimization has resulted in the development of potent and selective non-covalent inhibitors, thus bypassing the liabilities of the serine trap. Thirdly, oral bioavailability has been achieved while maintaining selectivity and efficacy through the incorporation of progressively less basic P1 groups. The duration of action of these compounds remains to be optimized. Other advances in thrombin inhibitor design have included the development of uncharged P1 groups and the discovery of two non-peptide templates.

  15. Epitope mapping with synthetic peptides of 52-kD SSA/Ro protein reveals heterogeneous antibody profiles in human autoimmune sera.

    PubMed Central

    Ricchiuti, V; Briand, J P; Meyer, O; Isenberg, D A; Pruijn, G; Muller, S

    1994-01-01

    The reactivity of autoantibodies present in the sera of 489 patients with Sjögren's syndrome (SS), systemic lupus erythematosus (SLE) and other autoimmune diseases was investigated by ELISA using recombinant 52-kD SSA/Ro protein (rRo52) and 39 overlapping synthetic peptides representing the entire sequence of Ro52. We report that IgG antibodies reacting with rRo52 were present in the sera of a large number of patients with SS (67% of patients with primary SS and 46% of patients with SS associated with SLE), whereas they were less frequent (10-25%) in SLE, rheumatoid arthritis (RA), juvenile chronic arthritis (JCA) and mixed connective tissue disease (MCTD), and absent in scleroderma. Among the 39 peptides tested, five were recognized by sera from 30-65% of patients with SS, namely peptides representing residues 2-11, 107-122, 107-126, 277-292 and 365-382. Patients with JCA had raised levels of IgG antibodies reacting with peptides 2-11 and 365-382, and 51% of patients with MCTD had raised levels of IgG antibodies reacting with peptide 365-382. None of the five peptides was recognized by more than 20% of sera from patients with SLE and RA. Interestingly, and of importance in the field of diagnostic tests based on peptides, the reactivity of antibodies to the Ro52 synthetic peptides varied greatly according to the origin of sera. Inhibition experiments using either patients' sera or antibodies induced in rabbits against Ro52 peptides showed that the four domains 2-11, 107-122, 277-292 and 365-382 are accessible on the surface of the Ro52 protein. These regions may thus be involved in the induction of specific antibodies in autoimmune patients. Images Fig. 5 PMID:7511075

  16. SU-E-T-780: Use Robustness Optimization (RO) Method to Improve the Planning Efficiency for Pencil Beam Scanning Cranial Spinal Irradiation

    SciTech Connect

    Ding, X; Zhang, J; Rosen, L; Wu, H; Traneus, E; Lin, H; Zhai, H

    2015-06-15

    Purpose: We evaluate the feasibility of using robustness optimization (RO) function to improve the planning efficiency of pencil beam scanning (PBS) craniospinal irradiation (CSI) with gradient matching technique. Methods: A CSI patient was planned with 2 lateral brain fields and 4 posterior fields to cover the entire spine to maximal field of 24 cm × 20 cm on a compact PBS gantry, ProteusONE. CSI plans were generated using traditional volumetric gradient dose optimization (VGDO) and robustness optimization (RO) method respectively. In traditional VGDO, besides the sectioned spine target volumes, gradient volume (GV) were generated as 4 equally spaced structures e.g. 80%, 60%, 40%, and 20% of prescription dose. In RO method, only sectioned spine target volumes with an overlap of 4cm were created. In the robustness optimization settings, 5mm uncertainty in superior and inferior direction was defined for auto gradient optimization. Dosimetric metrics of conformity number (CN), homogeneity index (HI), and maximal cord doses were compared in Raystation version 4.6.100.6. Results: In VGDO method, total 16 GV structures and five 100% dose level target structures were contoured compared to total 5 target structures in RO method which saves 30 min in contour. With the same PTV coverage (95% volume receive 30.6Gy prescription dose), maximum cord dose is 32.64Gy in VGDO and 31.94Gy in RO. HI is 1.03 and 1.04 for VGDO and RO respectively. CN is 0.93 and 0.94 for VGDO and RO respectively. Conclusions: The dosimetric comparison demonstrated both methods are equivalent in terms of plan quality. With robust optimization for CSI gradient matching, it efficiently reduces the amount of planning target contour structure by factor of 4 and thus improves the planning efficiency especially for 4 or more gradient junction area.

  17. Could CoRoT-7b and Kepler-10b be remnants of evaporated gas or ice giants?

    PubMed Central

    Leitzinger, M.; Odert, P.; Kulikov, Yu.N.; Lammer, H.; Wuchterl, G.; Penz, T.; Guarcello, M.G.; Micela, G.; Khodachenko, M.L.; Weingrill, J.; Hanslmeier, A.; Biernat, H.K.; Schneider, J.

    2011-01-01

    We present thermal mass loss calculations over evolutionary time scales for the investigation if the smallest transiting rocky exoplanets CoRoT-7b (∼1.68REarth) and Kepler-10b (∼1.416REarth) could be remnants of an initially more massive hydrogen-rich gas giant or a hot Neptune-class exoplanet. We apply a thermal mass loss formula which yields results that are comparable to hydrodynamic loss models. Our approach considers the effect of the Roche lobe, realistic heating efficiencies and a radius scaling law derived from observations of hot Jupiters. We study the influence of the mean planetary density on the thermal mass loss by placing hypothetical exoplanets with the characteristics of Jupiter, Saturn, Neptune, and Uranus to the orbital location of CoRoT-7b at 0.017 AU and Kepler-10b at 0.01684 AU and assuming that these planets orbit a K- or G-type host star. Our findings indicate that hydrogen-rich gas giants within the mass domain of Saturn or Jupiter cannot thermally lose such an amount of mass that CoRoT-7b and Kepler-10b would result in a rocky residue. Moreover, our calculations show that the present time mass of both rocky exoplanets can be neither a result of evaporation of a hydrogen envelope of a “Hot Neptune” nor a “Hot Uranus”-class object. Depending on the initial density and mass, these planets most likely were always rocky planets which could lose a thin hydrogen envelope, but not cores of thermally evaporated initially much more massive and larger objects. PMID:21969736

  18. Measurements of OH, HO 2+RO 2, H 2SO 4, and MSA at the South Pole during ISCAT 2000

    NASA Astrophysics Data System (ADS)

    Mauldin, R. L.; Kosciuch, E.; Henry, B.; Eisele, F. L.; Shetter, R.; Lefer, B.; Chen, G.; Davis, D.; Huey, G.; Tanner, D.

    2004-10-01

    Measurements of hydroxyl radical (OH), sulfuric acid (H2SO4) and methane sulfonic acid (MSA) together with the first HO2+RO2 observations at the South Pole are presented. These results were recorded as part of the Investigation of Sulfur Chemistry in the Antarctic Troposphere 2000 (ISCAT 2000) study. OH concentrations were found to be highly elevated, having a mean value over the time period of 15 November-30 December 2000 of 2.5×106 molecule cm-3, thus confirming the results from ISCAT 1998. Although data were more limited for the sum of HO2+RO2, a mean value of ∼7×107 molecule cm-3 was estimated. Typically, OH and HO2+RO2 both showed large day-to-day variability. Box model simulations suggest that most of this variability was a direct result of elevated and highly variable levels of nitric oxide. Comparisons of OH with overhead O3 column density measurements revealed that for certain time periods as much as a 30% enhancement occurred in OH as a result of decreases in column O3 levels. Like ISCAT 1998, the observational data for H2SO4 and MSA generally showed very low concentrations with mean values of 2.7×105 and 8×104 molecule cm-3, respectively. When compared against measured levels of particulate sulfate and methane sulfonate, these low gas phase concentrations indicate, as suggested by the more limited data from the ISCAT 1998 study, that local production of gas phase sulfur species contributes little to particle composition.

  19. Pulsations in the late-type Be star HD 50 209 detected by CoRoT

    NASA Astrophysics Data System (ADS)

    Diago, P. D.; Gutiérrez-Soto, J.; Auvergne, M.; Fabregat, J.; Hubert, A.-M.; Floquet, M.; Frémat, Y.; Garrido, R.; Andrade, L.; de Batz, B.; Emilio, M.; Espinosa Lara, F.; Huat, A.-L.; Janot-Pacheco, E.; Leroy, B.; Martayan, C.; Neiner, C.; Semaan, T.; Suso, J.; Catala, C.; Poretti, E.; Rainer, M.; Uytterhoeven, K.; Michel, E.; Samadi, R.

    2009-10-01

    Context: The presence of pulsations in late-type Be stars is still a matter of controversy. It constitutes an important issue to establish the relationship between non-radial pulsations and the mass-loss mechanism in Be stars. Aims: To contribute to this discussion, we analyse the photometric time series of the B8IVe star HD 50 209 observed by the CoRoT mission in the seismology field. Methods: We use standard Fourier techniques and linear and non-linear least squares fitting methods to analyse the CoRoT light curve. In addition, we applied detailed modelling of high-resolution spectra to obtain the fundamental physical parameters of the star. Results: We have found four frequencies which correspond to gravity modes with azimuthal order m=0,-1,-2,-3 with the same pulsational frequency in the co-rotating frame. We also found a rotational period with a frequency of 0.679 cd-1 (7.754 μHz). Conclusions: HD 50 209 is a pulsating Be star as expected from its position in the HR diagram, close to the SPB instability strip. Based on observations made with the CoRoT satellite, with FEROS at the 2.2 m telescope of the La Silla Observatory under the ESO Large Programme LP178.D-0361 and with Narval at the Télescope Bernard Lyot of the Pic du Midi Observatory. Current address: Valencian International University (VIU), José Pradas Gallen s/n, 12006 Castellón, Spain. Current address: Laboratoire AIM, CEA/DSM-CNRS-Université Paris Diderot; CEA, IRFU, SAp, centre de Saclay, 91191 Gif-sur-Yvette, France.

  20. Could CoRoT-7b and Kepler-10b be remnants of evaporated gas or ice giants?

    NASA Astrophysics Data System (ADS)

    Leitzinger, M.; Odert, P.; Kulikov, Yu. N.; Lammer, H.; Wuchterl, G.; Penz, T.; Guarcello, M. G.; Micela, G.; Khodachenko, M. L.; Weingrill, J.; Hanslmeier, A.; Biernat, H. K.; Schneider, J.

    2011-10-01

    We present thermal mass loss calculations over evolutionary time scales for the investigation if the smallest transiting rocky exoplanets CoRoT-7b (∼1.68REarth) and Kepler-10b (∼1.416REarth) could be remnants of an initially more massive hydrogen-rich gas giant or a hot Neptune-class exoplanet. We apply a thermal mass loss formula which yields results that are comparable to hydrodynamic loss models. Our approach considers the effect of the Roche lobe, realistic heating efficiencies and a radius scaling law derived from observations of hot Jupiters. We study the influence of the mean planetary density on the thermal mass loss by placing hypothetical exoplanets with the characteristics of Jupiter, Saturn, Neptune, and Uranus to the orbital location of CoRoT-7b at 0.017 AU and Kepler-10b at 0.01684 AU and assuming that these planets orbit a K- or G-type host star. Our findings indicate that hydrogen-rich gas giants within the mass domain of Saturn or Jupiter cannot thermally lose such an amount of mass that CoRoT-7b and Kepler-10b would result in a rocky residue. Moreover, our calculations show that the present time mass of both rocky exoplanets can be neither a result of evaporation of a hydrogen envelope of a “Hot Neptune” nor a “Hot Uranus”-class object. Depending on the initial density and mass, these planets most likely were always rocky planets which could lose a thin hydrogen envelope, but not cores of thermally evaporated initially much more massive and larger objects.

  1. Could CoRoT-7b and Kepler-10b be remnants of evaporated gas or ice giants?

    PubMed

    Leitzinger, M; Odert, P; Kulikov, Yu N; Lammer, H; Wuchterl, G; Penz, T; Guarcello, M G; Micela, G; Khodachenko, M L; Weingrill, J; Hanslmeier, A; Biernat, H K; Schneider, J

    2011-10-01

    We present thermal mass loss calculations over evolutionary time scales for the investigation if the smallest transiting rocky exoplanets CoRoT-7b (∼1.68REarth) and Kepler-10b (∼1.416REarth) could be remnants of an initially more massive hydrogen-rich gas giant or a hot Neptune-class exoplanet. We apply a thermal mass loss formula which yields results that are comparable to hydrodynamic loss models. Our approach considers the effect of the Roche lobe, realistic heating efficiencies and a radius scaling law derived from observations of hot Jupiters. We study the influence of the mean planetary density on the thermal mass loss by placing hypothetical exoplanets with the characteristics of Jupiter, Saturn, Neptune, and Uranus to the orbital location of CoRoT-7b at 0.017 AU and Kepler-10b at 0.01684 AU and assuming that these planets orbit a K- or G-type host star. Our findings indicate that hydrogen-rich gas giants within the mass domain of Saturn or Jupiter cannot thermally lose such an amount of mass that CoRoT-7b and Kepler-10b would result in a rocky residue. Moreover, our calculations show that the present time mass of both rocky exoplanets can be neither a result of evaporation of a hydrogen envelope of a "Hot Neptune" nor a "Hot Uranus"-class object. Depending on the initial density and mass, these planets most likely were always rocky planets which could lose a thin hydrogen envelope, but not cores of thermally evaporated initially much more massive and larger objects.

  2. Redox Indicator Mice Stably Expressing Genetically Encoded Neuronal roGFP: Versatile Tools to Decipher Subcellular Redox Dynamics in Neuropathophysiology

    PubMed Central

    Wagener, Kerstin C.; Kolbrink, Benedikt; Dietrich, Katharina; Kizina, Kathrin M.; Terwitte, Lukas S.; Kempkes, Belinda; Bao, Guobin

    2016-01-01

    Abstract Aims: Reactive oxygen species (ROS) and downstream redox alterations not only mediate physiological signaling but also neuropathology. For long, ROS/redox imaging was hampered by a lack of reliable probes. Genetically encoded redox sensors overcame this gap and revolutionized (sub)cellular redox imaging. Yet, the successful delivery of sensor-coding DNA, which demands transfection/transduction of cultured preparations or stereotaxic microinjections of each subject, remains challenging. By generating transgenic mice, we aimed to overcome limiting cultured preparations, circumvent surgical interventions, and to extend effectively redox imaging to complex and adult preparations. Results: Our redox indicator mice widely express Thy1-driven roGFP1 (reduction–oxidation-sensitive green fluorescent protein 1) in neuronal cytosol or mitochondria. Negative phenotypic effects of roGFP1 were excluded and its proper targeting and functionality confirmed. Redox mapping by ratiometric wide-field imaging reveals most oxidizing conditions in CA3 neurons. Furthermore, mitochondria are more oxidized than cytosol. Cytosolic and mitochondrial roGFP1s reliably report cell endogenous redox dynamics upon metabolic challenge or stimulation. Fluorescence lifetime imaging yields stable, but marginal, response ranges. We therefore developed automated excitation ratiometric 2-photon imaging. It offers superior sensitivity, spatial resolution, and response dynamics. Innovation and Conclusion: Redox indicator mice enable quantitative analyses of subcellular redox dynamics in a multitude of preparations and at all postnatal stages. This will uncover cell- and compartment-specific cerebral redox signals and their defined alterations during development, maturation, and aging. Cross-breeding with other disease models will reveal molecular details on compartmental redox homeostasis in neuropathology. Combined with ratiometric 2-photon imaging, this will foster our mechanistic understanding

  3. RoBuST: an integrated genomics resource for the root and bulb crop families Apiaceae and Alliaceae

    PubMed Central

    2010-01-01

    Background Root and bulb vegetables (RBV) include carrots, celeriac (root celery), parsnips (Apiaceae), onions, garlic, and leek (Alliaceae)—food crops grown globally and consumed worldwide. Few data analysis platforms are currently available where data collection, annotation and integration initiatives are focused on RBV plant groups. Scientists working on RBV include breeders, geneticists, taxonomists, plant pathologists, and plant physiologists who use genomic data for a wide range of activities including the development of molecular genetic maps, delineation of taxonomic relationships, and investigation of molecular aspects of gene expression in biochemical pathways and disease responses. With genomic data coming from such diverse areas of plant science, availability of a community resource focused on these RBV data types would be of great interest to this scientific community. Description The RoBuST database has been developed to initiate a platform for collecting and organizing genomic information useful for RBV researchers. The current release of RoBuST contains genomics data for 294 Alliaceae and 816 Apiaceae plant species and has the following features: (1) comprehensive sequence annotations of 3663 genes 5959 RNAs, 22,723 ESTs and 11,438 regulatory sequence elements from Apiaceae and Alliaceae plant families; (2) graphical tools for visualization and analysis of sequence data; (3) access to traits, biosynthetic pathways, genetic linkage maps and molecular taxonomy data associated with Alliaceae and Apiaceae plants; and (4) comprehensive plant splice signal repository of 659,369 splice signals collected from 6015 plant species for comparative analysis of plant splicing patterns. Conclusions RoBuST, available at http://robust.genome.com, provides an integrated platform for researchers to effortlessly explore and analyze genomic data associated with root and bulb vegetables. PMID:20691054

  4. Lithium and Isotopic Ratio Li6/Li7 in Magnetic roAp Stars as an Indicator of Active Processes

    NASA Astrophysics Data System (ADS)

    Polosukhina, N.; Shavrina, A.; Lyashko, D.; Nesvacil, N.; Drake, N.; Smirnova, M.

    2015-04-01

    The lines of lithium at 6708 Å and 6103 Å are analyzed in high resolution spectra of some sharp-lined and slowly rotating roAp stars. Three spectral synthesis codes— STARSP, ZEEMAN2, and SYNTHM—were used. New lines of rare earth elements (REE) from the DREAM database and the lines calculated on the basis of the NIST energy levels were included. Magnetic splitting and other line broadening processes were taken into account. For both lithium lines, the enhanced abundances of lithium in the atmospheres of the stars studied are obtained. The lithium abundance determined from the Li 6103 Å line is higher than that from the Li 6708 Å for all the stars. This may be evidence of vertical lithium stratification, abnormal temperature distribution, or unidentified blending of the 6103 Å line. Our work on two roAp stars, HD 83368 and HD 60435 (Shavrina et al. 2001) provides evidence of an enhanced lithium abundance near the magnetic-field poles. We can expect similar effects in the sharp-lined roAp stars. High lithium abundance for all the stars and the estimates of the 6Li/7Li ratio (0.2-0.5) can be explained by production of Li in the cosmic ray spallation reactions in the interstellar medium where the stars were born, and by preservation of the original 6Li and 7Li by strong magnetic fields of these stars. The values of the 6Li/7Li ratio expected from production by cosmic rays are about 0.5-0.8 (Knauth et al. 2003; Webber et al. 2002). New laboratory and theoretical gf-values for REE lines are necessary in order to refine our estimates of lithium abundances and the isotopic ratio.

  5. Gamma-secretase/Notch Signalling Pathway Inhibitor RO4929097 in Treating Patients With Advanced, Metastatic, or Recurrent Triple Negative Invasive Breast Cancer

    ClinicalTrials.gov

    2017-02-28

    Estrogen Receptor-negative Breast Cancer; HER2-negative Breast Cancer; Male Breast Cancer; Progesterone Receptor-negative Breast Cancer; Recurrent Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer; Stage IV Breast Cancer; Triple-negative Breast Cancer

  6. Gamma-Secretase/Notch Signalling Pathway Inhibitor RO4929097, Paclitaxel, and Carboplatin Before Surgery in Treating Patients With Stage II or Stage III Triple-Negative Breast Cancer

    ClinicalTrials.gov

    2015-09-03

    Estrogen Receptor Negative; HER2/Neu Negative; Progesterone Receptor Negative; Stage IIA Breast Cancer; Stage IIB Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer; Triple-Negative Breast Carcinoma

  7. Gamma-Secretase Inhibitor RO4929097 in Treating Young Patients With Relapsed or Refractory Solid Tumors, CNS Tumors, Lymphoma, or T-Cell Leukemia

    ClinicalTrials.gov

    2014-11-04

    Childhood Atypical Teratoid/Rhabdoid Tumor; Childhood Central Nervous System Choriocarcinoma; Childhood Central Nervous System Germinoma; Childhood Central Nervous System Mixed Germ Cell Tumor; Childhood Central Nervous System Teratoma; Childhood Central Nervous System Yolk Sac Tumor; Childhood Choroid Plexus Tumor; Childhood Craniopharyngioma; Childhood Ependymoblastoma; Childhood Grade I Meningioma; Childhood Grade II Meningioma; Childhood Grade III Meningioma; Childhood Infratentorial Ependymoma; Childhood Medulloepithelioma; Childhood Mixed Glioma; Childhood Oligodendroglioma; Childhood Supratentorial Ependymoma; Gonadotroph Adenoma; Pituitary Basophilic Adenoma; Pituitary Chromophobe Adenoma; Pituitary Eosinophilic Adenoma; Prolactin Secreting Adenoma; Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Anaplastic Large Cell Lymphoma; Recurrent Childhood Brain Stem Glioma; Recurrent Childhood Central Nervous System Embryonal Tumor; Recurrent Childhood Cerebellar Astrocytoma; Recurrent Childhood Cerebral Astrocytoma; Recurrent Childhood Ependymoma; Recurrent Childhood Grade III Lymphomatoid Granulomatosis; Recurrent Childhood Large Cell Lymphoma; Recurrent Childhood Lymphoblastic Lymphoma; Recurrent Childhood Medulloblastoma; Recurrent Childhood Pineoblastoma; Recurrent Childhood Small Noncleaved Cell Lymphoma; Recurrent Childhood Spinal Cord Neoplasm; Recurrent Childhood Subependymal Giant Cell Astrocytoma; Recurrent Childhood Supratentorial Primitive Neuroectodermal Tumor; Recurrent Childhood Visual Pathway and Hypothalamic Glioma; Recurrent Childhood Visual Pathway Glioma; Recurrent Pituitary Tumor; Recurrent/Refractory Childhood Hodgkin Lymphoma; T-cell Childhood Acute Lymphoblastic Leukemia; T-cell Large Granular Lymphocyte Leukemia; TSH Secreting Adenoma; Unspecified Childhood Solid Tumor, Protocol Specific

  8. VizieR Online Data Catalog: Seismology and spectroscopy of CoRoGEE red giants (Anders+, 2017)

    NASA Astrophysics Data System (ADS)

    Anders, F.; Chiappini, C.; Rodrigues, T. S.; Miglio, A.; Montalban, J.; Mosser, B.; Girardi, L.; Valentini, M.; Noels, A.; Morel, T.; Johnson, J. A.; Schultheis, M.; Baudin, F.; de Assis Peralta, R.; Hekker, S.; Themessl, N.; Kallinger, T.; Garcia, R. A.; Mathur, S.; Baglin, A.; Santiago, B. X.; Martig, M.; Minchev, I.; Steinmetz, M.; da Costa, L. N.; Maia, M. A. G.; Allende Prieto, C.; Cunha, K.; Beers, T. C.; Epstein, C.; Garcia Perez, A. E.; Garcia-Hernandez, D. A.; Harding, P.; Holtzman, J.; Majewski, S. R.; Meszaros, Sz.; Nidever, D.; Pan, K.; Pinsonneault, M.; Schiavon, R. P.; Schneider, D. P.; Shetrone, M. D.; Stassun, K.; Zamora, O.; Zasowski, G.

    2016-08-01

    For the 606 successfully observed stars, asteroseismic parameters from CoRoT, spectroscopic data from APOGEE (SDSS DR12), wide-band photometry from OBSCAT, APASS, SDSS, 2MASS, and WISE are presented. Additional information from the EXODAT archive, stellar parameters from PARAM (Rodrigues et al. 2014MNRAS.445.2758R), cross-matches to the APOGEE red-clump catalogue (Bovy et al. 2014ApJ...790..127B), the UCAC-4 catalogue (Zacharias et al., 2013, Cat. I/322), and derived stellar kinematics are also included. (2 data files).

  9. SpRoUTS (Space Robot Universal Truss System): Reversible Robotic Assembly of Deployable Truss Structures of Reconfigurable Length

    NASA Technical Reports Server (NTRS)

    Jenett, Benjamin; Cellucci, Daniel; Cheung, Kenneth

    2015-01-01

    Automatic deployment of structures has been a focus of much academic and industrial work on infrastructure applications and robotics in general. This paper presents a robotic truss assembler designed for space applications - the Space Robot Universal Truss System (SpRoUTS) - that reversibly assembles a truss from a feedstock of hinged andflat-packed components, by folding the sides of each component up and locking onto the assembled structure. We describe the design and implementation of the robot and show that the assembled truss compares favorably with prior truss deployment systems.

  10. VizieR Online Data Catalog: Planetary transit candidates in CoRoT SRc01 field (Erikson+, 2012)

    NASA Astrophysics Data System (ADS)

    Erikson, A.; Santerne, A.; Renner, S.; Barge, P.; Aigrain, S.; Alapini, A.; Almenara, J.-M.; Alonso, R.; Auvergne, M.; Baglin, A.; Benz, W.; Bonomo, A. S.; Borde, P.; Bouchy, F.; Bruntt, H.; Cabrera, J.; Carone, L.; Carpano, S.; Csizmadia, Sz.; Deleuil, M.; Deeg, H. J.; Diaz, R. F.; Dvorak, R.; Ferraz-Mello, S.; Fridlund, M.; Gandolfi, D.; Gazzano, J.-C.; Gillon, M.; Guenther, E. W.; Guillot, T.; Hatzes, A.; Hebrard, G.; Jorda, L.; Lammer, H.; Leger, A.; Llebaria, A.; Mayor, M.; Mazeh, T.; Moutou, C.; Ollivier, M.; Ofir, A.; Paetzold, M.; Pepe, F.; Pont, F.; Queloz, D.; Rabus, M.; Rauer, H.; Regulo, C.; Rouan, D.; Samuel, B.; Schneider, J.; Shporer, A.; Tingley, B.; Udry, S.; Wuchterl, G.

    2012-04-01

    Among the acquired data, we analyzed those for 1269 sources in the chromatic bands and 5705 in the monochromatic band. Instrumental noise and the stellar variability were treated with several detrending tools, to which several transit-search algorithms were subsequently applied. Fifty-one sources were classified as planetary transit candidates and 26 were followed up with ground-based observations. Until now, no planet has been detected in the CoRoT data from the SRc01 field. (1 data file).

  11. Seventy new non-eclipsing BEER binaries discovered in CoRoT lightcurves and confirmed by RVs from AAOmega

    NASA Astrophysics Data System (ADS)

    Tal-Or, Lev; Faigler, Simchon; Mazeh, Tsevi

    2015-09-01

    We applied the BEER algorithm to the CoRoT lightcurves from the first five LRc fields and identified 481 non-eclipsing BEER candidates with periodic lightcurve modulations and amplitudes of 0.5 - 87 mmag. Medium-resolution spectra of 281 candidates were obtained in a seven-night AAOmega radial-velocity (RV) campaign, with a precision of ˜ 1 km/s. The RVs confirmed the binarity of 70 of the BEER candidates, with periods of 0.3 - 10 days.

  12. Acyclic peptide inhibitors of amylases.

    PubMed

    Pohl, Nicola

    2005-12-01

    In this issue of Chemistry and Biology, a library screening approach reveals a linear octapeptide inhibitor of alpha-amylases reached by de novo design . The selected molecule shares characteristics with naturally occurring protein inhibitors -- a result that suggests general rules for the design of peptide-based amylase inhibitors may be achievable.

  13. CoRoT 101186644: A transiting low-mass dense M-dwarf on an eccentric 20.7-day period orbit around a late F-star. Discovered in the CoRoT lightcurves

    NASA Astrophysics Data System (ADS)

    Tal-Or, L.; Mazeh, T.; Alonso, R.; Bouchy, F.; Cabrera, J.; Deeg, H. J.; Deleuil, M.; Faigler, S.; Fridlund, M.; Hébrard, G.; Moutou, C.; Santerne, A.; Tingley, B.

    2013-05-01

    We present the study of the CoRoT transiting planet candidate 101186644, also named LRc01_E1_4780. Analysis of the CoRoT lightcurve and the HARPS spectroscopic follow-up observations of this faint (mV = 16) candidate revealed an eclipsing binary composed of a late F-type primary (Teff = 6090 ± 200 K) and a low-mass, dense late M-dwarf secondary on an eccentric (e = 0.4) orbit with a period of ~20.7 days. The M-dwarf has a mass of 0.096 ± 0.011 M⊙, and a radius of 0.104-0.006+0.026 R⊙, which possibly makes it the smallest and densest late M-dwarf reported so far. Unlike the claim that theoretical models predict radii that are 5-15% smaller than measured for low-mass stars, this one seems to have a radius that is consistent and might even be below the radius predicted by theoretical models. Based on observations made with the 1-m telescope at the Wise Observatory, Israel, the Swiss 1.2-m Leonhard Euler telescope at La Silla Observatory, Chile, the IAC-80 telescope at the Observatory del Teide, Canarias, Spain, and the 3.6-m telescope at La Silla Observatory (ESO), Chile (program 184.C-0639).

  14. [SGLT2 inhibitor].

    PubMed

    Kubota, Naoto; Kadowaki, Takashi

    2015-12-01

    SGLT2 is a glucose transporter which plays an important role for reabsorption of urinary glucose depending on the sodium concentration gradient. SGLT2 is mainly present in apical site of S1 segment of renal proximal tubule and accounts for approximately 90% of total urinary glucose reabsorption. SLC5a2, which codes SGLT2, is also known as the causative gene of familial renal glucosuria. SGLT2 inhibitors are attracting attention as newly developed oral anti-diabetic agents which improve glucose intolerance and also have an anti-obese effect by promoting urinary glucose excretion (UGE), which is a different pharmacological effect from other conventional anti-diabetic agents. In this review, we will discuss the effect of SGLT2 inhibitor on the regulation of glucose and lipid metabolism in type 2 diabetes.

  15. Comparative study of CD4 and CD45RO T cells and CD20 B cells in cerebrospinal fluid of syphilitic meningitis and tuberculous meningitis patients.

    PubMed

    Yu, Nian; Zhang, Qiao-Quan; Zhang, Kang; Xie, Yuan; Zhu, Hai-Qing; Lin, Xing-Jian; Di, Qing

    2016-09-01

    This study was to investigate the differences of lymphocyte in the cerebrospinal fluid (CSF) of patients with syphilis meningitis (SM) and tuberculous meningitis (TBM) for new diagnostic insights. Totally, 79 cases of SM and 45 cases of TBM were enrolled. In the CSF, the CD4, CD45RO or CD20 positive lymphocytes were detected by immunohistochemistry. The proportion of CD4 T cells in the CSF lymphocytes in patients with SM was significantly higher than that in patients with TBM (p < 0.05). After medical therapy, there was a significantly decline trend of the CD4 T-cell proportion in both groups (p < 0.05). The proportion of CD45RO T cells in CSF lymphocytes of patients with SM was less than that of patients with TBM (p < 0.05). After medical therapy, the positive ratio of CD45RO T cells was increased in the CSF of both group patients (p < 0.05). The proportion of CD20B cells in the CSF lymphocytes was not obviously different between the two groups during every stage. In conclusion, there are strong differences of CD4 and CD45RO T-cell ratio, but not the CD20 B cells in the meningitis. CD4 and CD45RO T cells in CSF are a useful complement in differentially diagnosing SM and TBM; it contributes to further understand the pathogenesis and prognosis of SM and TBM.

  16. Identifying the `true' radius of the hot sub-Neptune CoRoT-24b by mass-loss modelling

    NASA Astrophysics Data System (ADS)

    Lammer, H.; Erkaev, N. V.; Fossati, L.; Juvan, I.; Odert, P.; Cubillos, P. E.; Guenther, E.; Kislyakova, K. G.; Johnstone, C. P.; Lüftinger, T.; Güdel, M.

    2016-09-01

    For the hot exoplanets CoRoT-24b and CoRoT-24c, observations have provided transit radii RT of 3.7 ± 0.4R⊕ and 4.9 ± 0.5R⊕, and masses of ≤5.7M⊕ and 28 ± 11M⊕, respectively. We study their upper atmosphere structure and escape applying an hydrodynamic model. Assuming RT ≈ RPL, where RPL is the planetary radius at the pressure of 100 mbar, we obtained for CoRoT-24b unrealistically high thermally driven hydrodynamic escape rates. This is due to the planet's high temperature and low gravity, independent of the stellar EUV flux. Such high escape rates could last only for <100 Myr, while RPL shrinks till the escape rate becomes less than or equal to the maximum possible EUV-driven escape rate. For CoRoT-24b, RPL must be therefore located at ≈1.9-2.2R⊕ and high altitude hazes/clouds possibly extinct the light at RT. Our analysis constraints also the planet's mass to be 5-5.7M⊕. For CoRoT-24c, RPL and RT lie too close together to be distinguished in the same way. Similar differences between RPL and RT may be present also for other hot, low-density sub-Neptunes.

  17. The Drosophila roX1 RNA gene can overcome silent chromatin by recruiting the male-specific lethal dosage compensation complex.

    PubMed Central

    Kelley, Richard L; Kuroda, Mitzi I

    2003-01-01

    The Drosophila MSL complex consists of at least six proteins and two noncoding roX RNAs that mediate dosage compensation. It acts to remodel the male's X chromatin by covalently modifying the amino terminal tails of histones. The roX1 and roX2 genes are thought to be nucleation sites for assembly and spreading of MSL complexes into surrounding chromatin where they roughly double the rates of transcription. We generated many transgenic stocks in which the roX1 gene was moved from its normal location on the X to new autosomal sites. Approximately 10% of such lines displayed unusual sexually dimorphic expression patterns of the transgene's mini-white eye-color marker. Males often displayed striking mosaic pigmentation patterns similar to those seen in position-effect variegation and yet most inserts were in euchromatic locations. In many of these stocks, female mini-white expression was very low or absent. The male-specific activation of mini-white depended upon the MSL complex. We propose that these transgenes are inserted in several different types of repressive chromatin environments that inhibit mini-white expression. Males are able to overcome this silencing through the action of the MSL complex spreading from the roX1 gene and remodeling the local chromatin to allow transcription. The potency with which an ectopic MSL complex overcomes silent chromatin suggests that its normal action on the X must be under strict regulation. PMID:12807777

  18. Advanced treatment of textile dyeing secondary effluent using magnetic anion exchange resin and its effect on organic fouling in subsequent RO membrane.

    PubMed

    Yang, Cheng; Li, Li; Shi, Jialu; Long, Chao; Li, Aimin

    2015-03-02

    Strict regulations are forcing dyeing factory to upgrade existing waste treatment system. In this study, advanced treatment of dyeing secondary effluent by magnetic anion exchange resin (NDMP) was investigated and compared with ultrafiltration (UF); NDMP as a pre-treatment of reverse osmosis (RO) was also studied. NDMP resin (20 mL/L) gave higher removal of dissolved organic carbon (DOC) (83.9%) and colority (94.9%) than UF with a cut-off of 10 kDa (only 48.6% and 44.1%, respectively), showing that NDMP treatment was effective to meet the stringent discharge limit of DOC and colority. Besides, NDMP resin (20 mL/L) as a pretreatment of RO increased the permeate flux by 12.5% and reduced irreversible membrane fouling by 6.6%, but UF pretreatment did not mitigate RO membrane fouling. The results of excitation-emission matrix fluorescence spectra and resin fractions showed that NDMP had more efficient removal than UF for transphilic acid and hydrophilic fraction, such as protein-like organic matters and soluble microbial products, which contributed to a significant proportion of RO membrane fouling. In sum, NDMP resin treatment not only gave effective removal of DOC and colority of dyeing secondary effluent, but exhibited some improvement for RO membrane flux and irreversible fouling.

  19. Development of scale inhibitors

    SciTech Connect

    Gill, J.S.

    1996-12-01

    During the last fifty years, scale inhibition has gone from an art to a science. Scale inhibition has changed from simple pH adjustment to the use of optimized dose of designer polymers from multiple monomers. The water-treatment industry faces many challenges due to the need to conserve water, availability of only low quality water, increasing environmental regulations of the water discharge, and concern for human safety when using acid. Natural materials such as starch, lignin, tannin, etc., have been replaced with hydrolytically stable organic phosphates and synthetic polymers. Most progress in scale inhibition has come from the use of synergistic mixtures and copolymerizing different functionalities to achieve specific goals. Development of scale inhibitors requires an understanding of the mechanism of crystal growth and its inhibition. This paper discusses the historic perspective of scale inhibition and the development of new inhibitors based on the understanding of the mechanism of crystal growth and the use of powerful tools like molecular modeling to visualize crystal-inhibitor interactions.

  20. Effect of antiscalants on precipitation of an RO concentrate: metals precipitated and particle characteristics for several water compositions.

    PubMed

    Greenlee, Lauren F; Testa, Fabrice; Lawler, Desmond F; Freeman, Benny D; Moulin, Philippe

    2010-04-01

    Inland brackish water reverse osmosis (RO) is economically and technically limited by the large volume of salty waste (concentrate) produced. The use of a controlled precipitation step, followed by solid/liquid separation (filtration), has emerged as a promising side-stream treatment process to treat reverse osmosis concentrate and increase overall system recovery. The addition of antiscalants to the RO feed prevents precipitation within the membrane system but might have a deleterious effect on a concentrate treatment process that uses precipitation to remove problematic precipitates. The effects of antiscalant type and concentration on salt precipitation and precipitate particle morphology were evaluated for several water compositions. The primary precipitate for the synthetic brackish waters tested was calcium carbonate; the presence of magnesium, sulfate, minor ions, and antiscalant compounds affected the amount of calcium precipitated, as well as the phases of calcium carbonate formed during precipitation. Addition of antiscalant decreased calcium precipitation but increased incorporation of magnesium and sulfate into precipitating calcium carbonate. Antiscalants prevented the growth of nucleated precipitates, resulting in the formation of small (100-200 nm diameter) particles, as well as larger (6-10 microm) particles. Elemental analysis revealed changes in composition and calcium carbonate polymorph with antiscalant addition and antiscalant type. Results indicate that the presence of antiscalants does reduce the extent of calcium precipitation and can worsen subsequent filtration performance.

  1. Frequency comparison involving the Romanian primary length standard RO.1 within the framework of the EUROMET Project #498

    NASA Astrophysics Data System (ADS)

    Popescu, Gheorghe

    2001-06-01

    An international frequency comparison was carried out at the Bundesamt fuer Eich- und Vermessungswessen (BEV), Vienna, within the framework of the EUROMET Project #498 from August 29 to September 5, 1999. The frequency differences obtained when the RO.1 laser from the National Institute for Laser, Plasma and Radiation Physics (NILPRP), Romania, was compared with five lasers from Austria (BEV1), Czech Republic (PLD1), France (BIPM3), Poland (GUM1) and Hungary (OMH1) are reported. Frequency differences were computed by using the matrix determinations for the group d, e, f, g. Considering the frequency differences measured for a group of three lasers compared to each other, we call the closing frequency the difference between measured and expected frequency difference (resulting from the previous two measurements). For the RO1 laser, when the BIPM3 laser was the reference laser, the closing frequencies range from +8.1 kHz to - 3.8 kHz. The relative Allan standard deviation was used to express the frequency stability and resulted 3.8 parts in 1012 for 100 s sampling time and 14000 s duration of the measurements. The averaged offset frequency relative to the BIPM4 stationary laser was 5.6 kHz and the standard deviation was 9.9 kHz.

  2. GROUND-BASED NEAR-INFRARED OBSERVATIONS OF THE SECONDARY ECLIPSE OF CoRoT-2b

    SciTech Connect

    Alonso, R.; Deeg, H. J.; Rabus, M.; Kabath, P.

    2010-04-15

    We present the results of a ground-based search for the secondary eclipse of the 3.3 M {sub Jup} transiting planet CoRoT-2b. We performed near-infrared photometry using the LIRIS instrument on the 4.2 m William Herschel Telescope, in the H and K{sub s} filters. We monitored the star around two expected secondary eclipses in two nights under very good observing conditions. For the depth of the secondary eclipse, in the H band we found a 3{sigma} upper limit of 0.17%, whereas we detected a tentative eclipse with a depth of 0.16% {+-} 0.09% in the K{sub s} band. These depths can be translated into brightness temperatures of T{sub H} < 2250 K and T{sub K{sub s}}= 1890{sup +260}{sub -350} K, which indicate an inefficient re-distribution of the incident stellar flux from the planet's day side to its night side. Our results are in agreement with the CoRoT optical measurement (Alonso et al.) and with Spitzer 4.5 and 8 {mu}m results (Gillon et al.)

  3. GROUND-BASED DETECTIONS OF THERMAL EMISSION FROM CoRoT-1b AND WASP-12b

    SciTech Connect

    Zhao Ming; Swain, Mark R.; Monnier, John D.; Barman, Travis; Hinkley, Sasha

    2012-01-10

    We report a new detection of the H-band thermal emission of CoRoT-1b and two confirmation detections of the Ks-band thermal emission of WASP-12b at secondary eclipses. The H-band measurement of CoRoT-1b shows an eclipse depth of 0.145% {+-} 0.049% with a 3{sigma} percentile between 0.033% and 0.235%. This depth is consistent with the previous conclusions that the planet has an isothermal region with inefficient heat transport from day side to night side, and has a dayside thermal inversion layer at high altitude. The two Ks-band detections of WASP-12b show a joint eclipse depth of 0.299% {+-} 0.065%. This result agrees with the measurement of Croll and collaborators, providing independent confirmation of their measurement. The repeatability of the WASP-12b measurements also validates our data analysis method. Our measurements, in addition to a number of previous results made with other telescopes, demonstrate that ground-based observations are becoming widely available for characterization of atmospheres of hot Jupiters.

  4. How different is the composition of the fouling layer of wastewater reuse and seawater desalination RO membranes?

    PubMed

    Khan, Muhammad Tariq; Busch, Markus; Molina, Veronica Garcia; Emwas, Abdul-Hamid; Aubry, Cyril; Croue, Jean-Philippe

    2014-08-01

    To study the effect of water quality and operating parameters on membrane fouling, a comparative analysis of wastewater (WW) and seawater (SW) fouled reverse osmosis (RO) membranes was conducted. Membranes were harvested from SWRO and WWRO pilot plants located in Vilaseca (East Spain), both using ultrafiltration as pretreatment. The SWRO unit was fed with Mediterranean seawater and the WWRO unit was operated using secondary effluent collected from the municipal wastewater treatment plant. Lead and terminal SWRO and WWRO modules were autopsied after five months and three months of operation, respectively. Ultrastructural, chemical, and microbiological analyses of the fouling layers were performed. Results showed that the WWRO train had mainly bio/organic fouling at the lead position element and inorganic fouling at terminal position element, whereas SWRO train had bio/organic fouling at both end position elements. In the case of WWRO membranes, Betaproteobacteria was the major colonizing species; while Ca, S, and P were the major present inorganic elements. The microbial population of SWRO membranes was mainly represented by Alpha and Gammaproteobacteria. Ca, Fe, and S were the main identified inorganic elements of the fouling layer of SWRO membranes. These results confirmed that the RO fouling layer composition is strongly impacted by the source water quality.

  5. Increased CD45RO expression on T lymphocytes in mediastinal lymph node and pulmonary lesions of patients with pulmonary sarcoidosis.

    PubMed Central

    Fazel, S B; Howie, S E; Krajewski, A S; Lamb, D

    1994-01-01

    Sarcoidosis is characterized by a cell-mediated response mediated by the activation of CD4+ T lymphocytes in an environment lacking adequate numbers of regulatory CD8+ T lymphocytes. Immunohistological studies on frozen tissues have shown that sarcoid lesions have activated CD4 helper/inducer T lymphocytes at the centre of granulomata, whereas lymphocytes at the periphery are mainly CD8 suppressor/cytotoxic cells. In this study we investigated the immunohistological distribution of CD45 isoforms of T cells in 29 paraffin-embedded sarcoid lesions in mediastinal and open lung biopsies. Ten of these were assessed quantitatively, with single-staining of serial sections demonstrating a predominance of CD45RO memory T lymphocytes in granulomata and intergranulomatous areas. Ratios of CD45RO:CD45RA T lymphocytes (or the ratio of memory to naive T cells) were 42.0:1 for granulomata and 17.9:1 for intergranulomatous areas of sarcoid lesions counted. This finding is compatible with the hypothesis that nearly all the lymphocytes present in sarcoid lesions have been previously activated, and selectively home to sarcoid lesions. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 PMID:8137547

  6. Pharmaceuticals and pesticides in reclaimed water: Efficiency assessment of a microfiltration-reverse osmosis (MF-RO) pilot plant.

    PubMed

    Rodriguez-Mozaz, Sara; Ricart, Marta; Köck-Schulmeyer, Marianne; Guasch, Helena; Bonnineau, Chloe; Proia, Lorenzo; de Alda, Miren Lopez; Sabater, Sergi; Barceló, Damià

    2015-01-23

    Water reuse is becoming a common practice in several areas in the world, particularly in those impacted by water scarcity driven by climate change and/or by rising human demand. Since conventional wastewater treatment plants (WWTPs) are not able to efficiently remove many organic contaminants and pathogens, more advanced water treatment processes should be applied to WWTP effluents for water reclamation purposes. In this work, a pilot plant based on microfiltration (MF) followed by reverse osmosis (RO) filtration was applied to the effluents of an urban WWTP. Both the WWTP and the pilot plant were investigated with regards to the removal of a group of relevant contaminants widely spread in the environment: 28 pharmaceuticals and 20 pesticides. The combined treatment by the MF-RO system was able to quantitatively remove the target micropollutants present in the WWTP effluents to values either in the low ng/L range or below limits of quantification. Monitoring of water quality of reclaimed water and water reclamation sources is equally necessary to design the most adequate treatment procedures aimed to water reuse for different needs.

  7. Pulsation spectrum of δ Scuti stars: the binary HD 50870 as seen with CoRoT and HARPS

    NASA Astrophysics Data System (ADS)

    Mantegazza, L.; Poretti, E.; Michel, E.; Rainer, M.; Baudin, F.; García Hernández, A.; Semaan, T.; Alvarez, M.; Amado, P. J.; Garrido, R.; Mathias, P.; Moya, A.; Suárez, J. C.; Auvergne, M.; Baglin, A.; Catala, C.; Samadi, R.

    2012-06-01

    Aims: We present the results obtained with the CoRoT satellite for HD 50870, a δ Sct star which was observed for 114.4 d. The aim of these observations was to evaluate the results obtained for HD 50844, the first δ Sct star monitored with CoRoT, on a longer time baseline. Methods: The 307,570 CoRoT datapoints were analysed with different techniques. The photometric observations were complemented over 15 nights of high-resolution spectroscopy with HARPS on a baseline of 25 d. These spectra were analysed to study the line profile variations and to derive the stellar physical parameters. Some uvby photometric observations were also obtained to better characterize the pulsation modes. Results: HD 50870 proved to be a low-amplitude, long-period spectroscopic binary system seen almost pole-on (i ≃ 21°). The brighter component, which also has the higher rotational velocity (vsini = 37.5 km s-1), is a δ Sct-type variable with a full light amplitude variation of about 0.04 mag. There is a dominant axisymmetric mode (17.16 d-1). Moreover, there are two groups of frequencies (about 19) in the intervals 6 - 9 and 13 - 18 d-1, with amplitudes ranging from a few mmag to 0.3 mmag. After the detection of about 250 terms (corresponding to an amplitude of about 0.045 mmag) a flat plateau appears in the power spectrum in the low-frequency region up to about 35 d-1. We were able to detect this plateau only thanks to the short cadence sampling of the CoRoT measurements (32 s). The density distribution vs. frequency of the detected frequencies seems to rule out the possibility that this plateau is the result of a process with a continuum power spectrum. The spacings of the strongest modes suggest a quasi-periodic pattern. We failed to find a satisfactory seismic model that simultaneously matches the frequency range, the position in the HR diagram, and the quasi-periodic pattern interpreted as a large separation. Nineteen modes were detected spectroscopically from the line profile

  8. Low-amplitude rotational modulation rather than pulsations in the CoRoT B-type supergiant HD 46769

    NASA Astrophysics Data System (ADS)

    Aerts, C.; Simón-Díaz, S.; Catala, C.; Neiner, C.; Briquet, M.; Castro, N.; Schmid, V. S.; Scardia, M.; Rainer, M.; Poretti, E.; Pápics, P. I.; Degroote, P.; Bloemen, S.; Østensen, R. H.; Auvergne, M.; Baglin, A.; Baudin, F.; Michel, E.; Samadi, R.

    2013-09-01

    Aims: We aim to detect and interpret photometric and spectroscopic variability of the bright CoRoT B-type supergiant target HD 46769 (V = 5.79). We also attempt to detect a magnetic field in the target. Methods: We analyse a 23-day oversampled CoRoT light curve after detrending and spectroscopic follow-up data using standard Fourier analysis and phase dispersion minimization methods. We determine the fundamental parameters of the star, as well as its abundances from the most prominent spectral lines. We perform a Monte Carlo analysis of spectropolarimetric data to obtain an upper limit of the polar magnetic field, assuming a dipole field. Results: In the CoRoT data, we detect a dominant period of 4.84 d with an amplitude of 87 ppm and some of its (sub-)multiples. Given the shape of the phase-folded light curve and the absence of binary motion, we interpret the dominant variability in terms of rotational modulation, with a rotation period of 9.69 d. Subtraction of the rotational modulation signal does not reveal any sign of pulsations. Our results are consistent with the absence of variability in the Hipparcos light curve. The spectroscopy leads to a projected rotational velocity of 72 ± 2 km s-1 and does not reveal periodic variability or the need to invoke macroturbulent line broadening. No signature of a magnetic field is detected in our data. A field stronger than ~500 G at the poles can be excluded, unless the possible non-detected field were more complex than dipolar. Conclusions: The absence of pulsations and macroturbulence of this evolved B-type supergiant is placed into the context of instability computations and of observed variability of evolved B-type stars. Based on CoRoT space-based photometric data; the CoRoT space mission was developed and operated by the French space agency CNES, with the participation of ESA's RSSD and Science Programmes, Austria, Belgium, Brazil, Germany, and Spain. Based on observations collected at La Silla Observatory, ESO

  9. Fresh water production from municipal waste water with RO membrane technology and its application for agriculture and industry in arid area

    NASA Astrophysics Data System (ADS)

    Yokoyama, F.

    2015-04-01

    One of the biggest problems of the 21st century is the global water shortage. Therefore it is difficult to increase the quantity of conventional water resources such as surface water and groundwater for agriculture and industry in arid area. Technical advancement in water treatment membrane technology including RO membrane has been remarkable especially in recent years. As the pore size of RO membrane is less than one nanometer, it is possible to produce the fresh water, which satisfies the drinking water quality standards, with utilizing RO membrane. In this report a new fresh water resource from municipal waste water is studied to apply to the plant factory which is the water saving type agriculture and industry in arid area.

  10. Determination of the Contamination Rate and the Associated Error for Targets Observed by CoRoT in the Exoplanet Channel

    NASA Astrophysics Data System (ADS)

    Gardes, B.; Chabaud, P.-Y.; Guterman, P.

    2012-09-01

    In the CoRoT exoplanet field of view, photometric measurements are obtained by aperture integration using a generic collection of masks. The total flux held within the photometric mask may be split in two parts, the target flux itself and the flux due to the nearest neighbours considered as contaminants. So far ExoDat (http://cesam.oamp.fr/exodat) gives a rough estimate of the contamination rate for all potential exoplanet targets (level-0) based on generic PSF shapes built before CoRoT launch. Here, we present the updated estimate of the contamination rate (level-1) with its associated error. This estimate is done for each target observed by CoRoT in the exoplanet channel using a new catalog of PSF built from the first available flight images and taking into account the line of sight of the satellite (i.e. the satellite orientation).

  11. Characterisation of the contribution of the GABA-benzodiazepine α1 receptor subtype to [(11)C]Ro15-4513 PET images.

    PubMed

    Myers, James F M; Rosso, Lula; Watson, Ben J; Wilson, Sue J; Kalk, Nicola J; Clementi, Nicoletta; Brooks, David J; Nutt, David J; Turkheimer, Federico E; Lingford-Hughes, Anne R

    2012-04-01

    This positron emission tomography (PET) study aimed to further define selectivity of [(11)C]Ro15-4513 binding to the GABARα5 relative to the GABARα1 benzodiazepine receptor subtype. The impact of zolpidem, a GABARα1-selective agonist, on [(11)C]Ro15-4513, which shows selectivity for GABARα5, and the nonselective benzodiazepine ligand [(11)C]flumazenil binding was assessed in humans. Compartmental modelling of the kinetics of [(11)C]Ro15-4513 time-activity curves was used to describe distribution volume (V(T)) differences in regions populated by different GABA receptor subtypes. Those with low α5 were best fitted by one-tissue compartment models; and those with high α5 required a more complex model. The heterogeneity between brain regions suggested spectral analysis as a more appropriate method to quantify binding as it does not a priori specify compartments. Spectral analysis revealed that zolpidem caused a significant V(T) decrease (~10%) in [(11)C]flumazenil, but no decrease in [(11)C]Ro15-4513 binding. Further analysis of [(11)C]Ro15-4513 kinetics revealed additional frequency components present in regions containing both α1 and α5 subtypes compared with those containing only α1. Zolpidem reduced one component (mean±s.d.: 71%±41%), presumed to reflect α1-subtype binding, but not another (13%±22%), presumed to reflect α5. The proposed method for [(11)C]Ro15-4513 analysis may allow more accurate selective binding assays and estimation of drug occupancy for other nonselective ligands.

  12. Removal of organic micro-pollutants (phenol, aniline and nitrobenzene) via forward osmosis (FO) process: Evaluation of FO as an alternative method to reverse osmosis (RO).

    PubMed

    Cui, Yue; Liu, Xiang-Yang; Chung, Tai-Shung; Weber, Martin; Staudt, Claudia; Maletzko, Christian

    2016-03-15

    In this study, we have explored and compared the effectiveness of using (1) lab-fabricated forward osmosis (FO) membranes under both FO and reverse osmosis (RO) modes and (2) commercially available RO membranes under the RO mode for the removal of organic micro-pollutants. The lab-fabricated FO membranes are thin film composite (TFC) membranes consisting of a polyamide layer and a porous substrate cast from three different materials; namely, Matrimid, polyethersulfone (PESU) and sulfonated polyphenylene sulfone (sPPSU). The results show that the FO mode is superior to the RO mode in the removal of phenol, aniline and nitrobenzene from wastewater. The rejections of all three TFC membranes to all the three organic micro-pollutants under the FO processes are higher than 72% and can be even higher than 90% for aniline when a 1000 ppm aromatic aqueous solution and 1 M NaCl are employed as feeds. These performances outperform the results obtained from themselves and commercially available RO membranes under the RO mode. In addition, the rejection can be maintained even when treating a more concentrated feed solution (2000 ppm). The removal performance can be further enhanced by using a more concentrated draw solution (2 M). The water flux is almost doubled, and the rejection increment can reach up to 17%. Moreover, it was observed that annealing as a post-treatment would help compact the membrane selective layer and further enhance the separating efficiency. The obtained organic micro-pollutant rejections and water fluxes under various feasible operating conditions indicate that the FO process has potential to be a viable treatment for wastewater containing organic micro-pollutants.

  13. Proteomics study of extracellular fibrinolytic proteases from Bacillus licheniformis RO3 and Bacillus pumilus 2.g isolated from Indonesian fermented food

    NASA Astrophysics Data System (ADS)

    Nur Afifah, Diana; Rustanti, Ninik; Anjani, Gemala; Syah, Dahrul; Yanti; Suhartono, Maggy T.

    2017-02-01

    This paper presents the proteomics study which includes separation, identification and characterization of proteins. The experiment on Indonesian fermented food such as extracellular fibrinolytic protease from Bacillus licheniformis RO3 and Bacillus pumilus 2.g isolated from red oncom and tempeh gembus was conducted. The experimental works comprise the following steps: (1) a combination of one- and two-dimensional electrophoresis analysis, (2) mass spectrometry analysis using MALDI-TOF-MS and (3) investigation using protein database. The result suggested that there were new two protein fractions of B. licheniformis RO3 and three protein fractions of B. pumilus 2.g. These result has not been previously reported.

  14. Magnetic activity in the photosphere of CoRoT-Exo-2a. Active longitudes and short-term spot cycle in a young Sun-like star

    NASA Astrophysics Data System (ADS)

    Lanza, A. F.; Pagano, I.; Leto, G.; Messina, S.; Aigrain, S.; Alonso, R.; Auvergne, M.; Baglin, A.; Barge, P.; Bonomo, A. S.; Boumier, P.; Collier Cameron, A.; Comparato, M.; Cutispoto, G.; de Medeiros, J. R.; Foing, B.; Kaiser, A.; Moutou, C.; Parihar, P. S.; Silva-Valio, A.; Weiss, W. W.

    2009-01-01

    Context: The space experiment CoRoT has recently detected transits by a hot Jupiter across the disc of an active G7V star (CoRoT-Exo-2a) that can be considered as a good proxy for the Sun at an age of approximately 0.5 Gyr. Aims: We present a spot modelling of the optical variability of the star during 142 days of uninterrupted observations performed by CoRoT with unprecedented photometric precision. Methods: We apply spot modelling approaches previously tested in the case of the Sun by modelling total solar irradiance variations, a good proxy for the optical flux variations of the Sun as a star. The best results in terms of mapping of the surface brightness inhomogeneities are obtained by means of maximum entropy regularized models. To model the light curve of CoRoT-Exo-2a, we take into account the photometric effects of both cool spots and solar-like faculae, adopting solar analogy. Results: Two active longitudes initially on opposite hemispheres are found on the photosphere of CoRoT-Exo-2a with a rotation period of 4.522 ± 0.024 days. Their separation changes by ≈80° during the time span of the observations. From this variation, a relative amplitude of the surface differential rotation lower than ~1 percent is estimated. Individual spots form within the active longitudes and show an angular velocity ~1 percent lower than that of the longitude pattern. The total spotted area shows a cyclic oscillation with a period of 28.9 ± 4.3 days, which is close to 10 times the synodic period of the planet as seen by the rotating active longitudes. We discuss the effects of solar-like faculae on our models, finding indications of a facular contribution to the optical flux variations of CoRoT-Exo-2a being significantly smaller than in the present Sun. Conclusions: The implications of such results for the internal rotation of CoRoT-Exo-2a are discussed, based on solar analogy. A possible magnetic star-planet interaction is suggested by the cyclic variation of the spotted

  15. Radical chemistry at a rural site (Wangdu) in the North China Plain: observation and model calculations of OH, HO2 and RO2 radicals

    NASA Astrophysics Data System (ADS)

    Tan, Zhaofeng; Fuchs, Hendrik; Lu, Keding; Hofzumahaus, Andreas; Bohn, Birger; Broch, Sebastian; Dong, Huabin; Gomm, Sebastian; Häseler, Rolf; He, Lingyan; Holland, Frank; Li, Xin; Liu, Ying; Lu, Sihua; Rohrer, Franz; Shao, Min; Wang, Baolin; Wang, Ming; Wu, Yusheng; Zeng, Limin; Zhang, Yinsong; Wahner, Andreas; Zhang, Yuanhang

    2017-01-01

    A comprehensive field campaign was carried out in summer 2014 in Wangdu, located in the North China Plain. A month of continuous OH, HO2 and RO2 measurements was achieved. Observations of radicals by the laser-induced fluorescence (LIF) technique revealed daily maximum concentrations between (5-15) × 106 cm-3, (3-14) × 108 cm-3 and (3-15) × 108 cm-3 for OH, HO2 and RO2, respectively. Measured OH reactivities (inverse OH lifetime) were 10 to 20 s-1 during daytime. The chemical box model RACM 2, including the Leuven isoprene mechanism (LIM), was used to interpret the observed radical concentrations. As in previous field campaigns in China, modeled and measured OH concentrations agree for NO mixing ratios higher than 1 ppbv, but systematic discrepancies are observed in the afternoon for NO mixing ratios of less than 300 pptv (the model-measurement ratio is between 1.4 and 2 in this case). If additional OH recycling equivalent to 100 pptv NO is assumed, the model is capable of reproducing the observed OH, HO2 and RO2 concentrations for conditions of high volatile organic compound (VOC) and low NOx concentrations. For HO2, good agreement is found between modeled and observed concentrations during day and night. In the case of RO2, the agreement between model calculations and measurements is good in the late afternoon when NO concentrations are below 0.3 ppbv. A significant model underprediction of RO2 by a factor of 3 to 5 is found in the morning at NO concentrations higher than 1 ppbv, which can be explained by a missing RO2 source of 2 ppbv h-1. As a consequence, the model underpredicts the photochemical net ozone production by 20 ppbv per day, which is a significant portion of the daily integrated ozone production (110 ppbv) derived from the measured HO2 and RO2. The additional RO2 production from the photolysis of ClNO2 and missing reactivity can explain about 10 % and 20 % of the discrepancy, respectively. The underprediction of the photochemical ozone

  16. Phosphinic peptides, the first potent inhibitors of astacin, behave as extremely slow-binding inhibitors.

    PubMed Central

    Yiallouros, I; Vassiliou, S; Yiotakis, A; Zwilling, R; Stöcker, W; Dive, V

    1998-01-01

    A series of phosphinic pseudo-peptides varying in length and composition have been designed as inhibitors of the crayfish zinc endopeptidase astacin, the prototype of the astacin family and of the metzincin superfamily of metalloproteinases. The most efficient phosphinic peptide, fluorenylmethyloxycarbonyl-Pro-Lys-PhePsi(PO2CH2)Ala-P ro-Leu-Val, binds to astacin with a Ki value of 42 nM, which is about three orders of magnitude below the corresponding values for previously used hydroxamic acid derivatives. However, the rate constants for association (kon = 96.8 M-1.s-1) and dissociation (koff = 4.1 x 10(-6) s-1) are evidence for the extremely slow binding behaviour of this compound. N-terminally or C-terminally truncated phosphinic analogues of this parent molecule are much less potent, indicating a critical role of the peptide size on the potency. In particular, omission of the N-terminal proline residue leads to a 40-fold increase in Ki which is mostly due to a 75-fold higher koff value. These findings are consistent with the previously solved crystal structure of astacin complexed with one of the phosphinic peptides, benzyloxycarbonyl-Pro-Lys-PhePsi(PO2CH2)Ala-Pro-O-methyl, Ki = 14 microM [Grams, Dive, Yiotakis, Yiallouros, Vassiliou, Zwilling, Bode and Stöcker (1996) Nature Struct. Biol. 3, 671-675]. This structure also reveals that the phosphinic group binds to the active site as a transition-state analogue. The extremely slow binding behaviour of the phosphinic peptides is discussed in the light of the conformational changes involving a unique 'tyrosine switch' in the structure of astacin upon inhibitor binding. The phosphinic peptides may provide a rational basis for the design of drugs directed towards other members of the astacin family which, like bone morphogenetic protein 1 (BMP1; i.e. the procollagen C-proteinase), have become targets of pharmacological research. PMID:9531473

  17. Tackling ALK in non-small cell lung cancer: the role of novel inhibitors

    PubMed Central

    Facchinetti, Francesco; Di Maio, Massimo; Graziano, Paolo; Bria, Emilio; Rossi, Giulio; Novello, Silvia

    2016-01-01

    Crizotinib is an oral inhibitor of anaplastic lymphoma kinase (ALK) with remarkable clinical activity in patients suffering from ALK-rearranged non-small cell lung cancer (NSCLC), accounting to its superiority compared to chemotherapy. Unfortunately, virtually all ALK-rearranged tumors acquire resistance to crizotinib, frequently within one year since the treatment initiation. To date, therapeutic strategies to overcome crizotinib resistance have focused on the use of more potent and structurally different compounds. Second-generation ALK inhibitors such as ceritinib (LDK378), alectinib (CH5424802/RO5424802) and brigatinib (AP26113) have shown relevant clinical activity, consequently fostering their rapid clinical development and their approval by health agencies. The third-generation inhibitor lorlatinib (PF-06463922), selectively active against ALK and ROS1, harbors impressive biological potency; its efficacy in reversing resistance to crizotinib and to other ALK inhibitors is being proven by early clinical trials. The NTRK1-3 and ROS1 inhibitor entrectinib (RXDX-101) has been reported to act against NSCLC harboring ALK fusion proteins too. Despite the quick development of these novel agents, several issues remain to be discussed in the treatment of patients suffering from ALK-rearranged NSCLC. This position paper will discuss the development, the current evidence and approvals, as long as the future perspectives of new ALK inhibitors beyond crizotinib. Clinical behaviors of ALK-rearranged NSCLC vary significantly among patients and differential molecular events responsible of crizotinib resistance account for the most important quote of this heterogeneity. The precious availability of a wide range of active anti-ALK compounds should be approached in a critical and careful perspective, in order to develop treatment strategies tailored on the disease evolution of every single patient. PMID:27413712

  18. BEER Analysis of Kepler and CoRoT Light Curves III. Sixty New Non-Eclipsing BEER Binaries Discovered in CoRoT Light Curves Confirmed by RVs from AAOmega

    NASA Astrophysics Data System (ADS)

    Tal-Or, L.; Faigler, S.; Mazeh, T.

    2015-07-01

    We have applied the BEER algorithm (Faigler& Mazeh 2011) to the CoRoT white-light curves from the first five LRc fields. We have found 491 non-eclipsing BEER candidates with periodic photometric modulations and amplitudes of 0.5-80 mmag. Medium-resolution spectra of 281 candidates were obtained in a seven-night AAOmega radial-velocity (RV) campaign, with a precision of ˜1 km s-1. The RVs confirmed the binarity of at least 60 of the BEER candidates, with RV semi-amplitudes ranging from 6 to 115 km s-1, and periods from 0.3 to 10 days. We detected an F-type star that may possibly have a brown dwarf companion in a 0.7-day period orbit.

  19. [Tyrosine kinase inhibitors].

    PubMed

    Robert, Jacques

    2011-11-01

    Membrane receptors with tyrosine kinase activity and cytoplasmic tyrosine kinases have emerged as important potential targets in oncology. Starting from basic structures such as anilino-quinazoline, numerous compounds have been synthesised, with the help of tyrosine kinase crystallography, which has allowed to optimise protein-ligand interactions. The catalytic domains of all kinases present similar three-dimensional structures, which explains that it may be difficult to identify molecules having a high specificity for a given tyrosine kinase. Some tyrosine kinase inhibitors are relatively specific for epidermal growth factor receptor (EGFR) such as géfitinib and erlotinib; other are mainly active against platelet-derived growth factor receptor (PDGFR) and the receptor KIT, such as imatinib or nilotinib, and other against vascular endothelial growth factor (VEGF) receptors involved in angiogenesis, such as sunitinib and sorafenib. The oral formulation of tyrosine kinase inhibitors is well accepted by the patients but may generate sometimes compliance problems requiring pharmacokinetic monitoring. This chemical family is in full expansion and several dozens of compounds have entered clinical trials.

  20. An analysis of the CoRoT-2 system: a young spotted star and its inflated giant planet

    NASA Astrophysics Data System (ADS)

    Guillot, T.; Havel, M.

    2011-03-01

    Context. CoRoT-2b is one of the most anomalously large exoplanet known. Given its high mass, its large radius cannot be explained by standard evolution models. Interestingly, the planet's parent star is an active, rapidly rotating solar-like star with with spots covering a large fraction (7-20%) of its visible surface. Aims: We attempt to constrain the properties of the star-planet system and understand whether the planet's inferred large size may be caused a systematic error in the inferred parameters, and if not, how it can be explained. Methods: We combine stellar and planetary evolution codes based on all available spectroscopic and photometric data to obtain self-consistent constraints on the system parameters. Results: We find no systematic error in the stellar modeling (including spots and stellar activity) that would cause a ~10% reduction in size of the star and thus the planet. Two classes of solutions are found: the usual main-sequence solution for the star yields for the planet a mass of 3.67 ± 0.13 MJ, a radius of 1.55 ± 0.03 RJ for an age that is at least 130 Ma and should be younger than 500 Ma given the star's rapid rotation and significant activity. We identify another class of solutions on the pre-main sequence, for which the planet's mass is 3.45 ± 0.27 MJ and its radius is 1.50 ± 0.06 RJ for an age of 30 to 40 Ma. These extremely young solutions provide the simplest explanation of the planet's size that can then be matched by a simple contraction from an initially hot, expanded state, if the atmospheric opacities are larger by a factor of ~3 than usually assumed for solar composition atmospheres. Other solutions imply that the present inflated radius of CoRoT-2b is transient and the result of an event that occurred less than 20 Ma ago, i.e., a giant impact with another Jupiter-mass planet, or interactions with another object in the system that caused a significant rise in the eccentricity followed by the rapid circularization of its orbit

  1. Synthesis of Lysine Methyltransferase Inhibitors

    NASA Astrophysics Data System (ADS)

    Ye, Tao; Hui, Chunngai

    2015-07-01

    Lysine methyltransferase which catalyze methylation of histone and nonhistone proteins, play a crucial role in diverse biological processes and has emerged as a promising target for the development of various human diseases, including cancer, inflammation, and psychiatric disorders. However, inhibiting Lysine methyltransferases selectively has presented many challenges to medicinal chemists. During the past decade, lysine methyltransferase inhibitors covering many different structural classes have been designed and developed. In this review, we describe the development of selective, small-molecule inhibitors of lysine methyltransferases with an emphasis on their discovery and chemical synthesis. We highlight the current state of lysine methyltransferase inhibitors and discuss future directions and opportunities for lysine methyltransferase inhibitor discovery.

  2. Comparative effects of continuous infusion of mCPP, Ro 60-0175 and d-fenfluramine on food intake, water intake, body weight and locomotor activity in rats.

    PubMed

    Vickers, S P; Benwell, K R; Porter, R H; Bickerdike, M J; Kennett, G A; Dourish, C T

    2000-07-01

    1. The aim of the study was to compare the effects of 14 day subcutaneous infusion of the 5-HT(2C) receptor agonists, m-chlorophenylpiperazine (mCPP, 12 mg kg(-1) day(-1)) and Ro 60-0175 (36 mg kg(-1) day(-1)) and the 5-HT releasing agent and re-uptake inhibitor, d-fenfluramine (6 mg kg(-1) day(-1)), on food and water intake, body weight gain and locomotion in lean male Lister hooded rats. 2. Chronic infusion of all three drugs significantly reduced food intake and attenuated body weight gain. In contrast, drug infusion did not lead to significant reductions in locomotor activity in animals assessed 2 and 13 days after pump implantation. 3. In a subsequent 14 day study that was designed to identify possible tolerance during days 7 - 14, animals were given a subcutaneous infusion of mCPP (12 mg kg(-1) day(-1)) or d-fenfluramine (6 mg kg(-1) day(-1)) for either 7 or 14 days. During the first 7 days both drugs significantly reduced body weight gain compared to saline-infused controls; however, from day 7 onwards animals withdrawn from drug treatment exhibited an increase in body weight such that by day 14 they were significantly heavier than their 14-day drug-treated counterparts. 4. Both mCPP and d-fenfluramine reduced daily food intake throughout the infusion periods. For 14-day treated animals this hypophagia was marked during the initial week of the study but only minor during the second week. In light of the sustained drug effect on body weight, the data suggest that weight loss by 5-HT(2C) receptor stimulation may be only partly dependent on changes in food consumption and that 5-HT(2C) receptor agonists may have effects on thermogenesis. 5. These data suggest tolerance does not develop to the effects of d-fenfluramine, mCPP and Ro 60-0175 on rat body weight gain.

  3. Te-Rich argyrodite occurrence in Roşia Montană ore deposit, Apuseni Mountains, Romania

    NASA Astrophysics Data System (ADS)

    Bailly, Laurent; Tămaş, Călin-Gabriel; Minuţ, Adrian

    2005-06-01

    A new argyrodite occurrence has been discovered in the Roşia Montană ore deposit located in the South Apuseni Mountains, Romania. Argyrodite is associated with common base metal sulfides and sulfosalts (galena, sphalerite, chalcopyrite, tetrahedrite ± alabandite, pyrite, and marcasite), tellurides (hessite, altaite, sylvanite) and rare electrum grains in the Ag-rich Cârnicel vein hosted by an extracraterial phreatomagmatic breccia within the Cârnic massif. SEM and EPMA analyses revealed that this argyrodite is Te-rich and a mean Ag 8.04Ge 0.9Te 2.07S 3.77 formula was calculated. This phase could be the germaniferous equivalent of the previously-described Te-rich canfieldite. To cite this article: L. Bailly et al., C. R. Geoscience 337 (2005).

  4. Spontaneous Remission of Congenital Complete Atrioventricular Block in Anti-Ro/La Antibody-Negative Monozygotic Twins: Case Report

    PubMed Central

    Kasar, Taner; Saygı, Murat; Özyılmaz, İsa; Ergül, Yakup

    2017-01-01

    Background: Congenital complete atrioventricular block without any structural heart disease and anti-Ro/La negativity is very rare. Discordant complete atrioventricular block, which is more frequently defined in the literature as an autoimmune mechanism, is much more rare in monozygotic twins. Case Report: The 26-year-old healthy mother had given birth in her first spontaneous, uneventful pregnancy to monozygotic twins at week 35. While the first twin’s physical examination proved her to be normal with a pulse rate consistent with her age, the second twin had a pulse rate of approximately 40 beats/minute.The patient was confirmed to have congenital complete atrioventricular block. Conclusion: Despite this case appears to be an isolated one, a discordant complete atrioventricular block regression without any autoimmune evidence should be included in the differential diagnosis of bradycardia in infants. PMID:28251027

  5. Comment on "Propionaldehyde infrared cross-sections and band strengths" by B. Köroğlu et al. [1

    NASA Astrophysics Data System (ADS)

    Richter, Wagner Eduardo; Bruns, Roy Edward

    2016-08-01

    The propionaldehyde infrared regional integrated area reported by Köroğlu et al. were re-examined. Even though the spectrum seems to be recorded correctly, the comparison between their values with the data obtained by the integration of the propionaldehyde spectrum available in the PNNL database suggests that a scaling factor of 2.3025 (the ratio between ln and log bases) is the reason for their results being lower than those expected based on other literature values and quantum chemical estimates. Revised values were then reported for the four spectral regions evaluated by these authors, resulting in a much better agreement between both theoretical and experimental results for not only for this molecule but also for others like acetone and acetaldehyde.

  6. TU-CD-BRD-04: UCLA Experience, with Focus On Developing Metrics and Using RO-ILS

    SciTech Connect

    Beron, P.

    2015-06-15

    It has long been standard practice in radiation oncology to report internally when a patient’s treatment has not gone as planned and to report events to regulatory agencies when legally required. Most potential errors are caught early and never affect the patient. Quality assurance steps routinely prevent errors from reaching the patient, and these “near misses” are much more frequent than treatment errors. A growing number of radiation oncology facilities have implemented incident learning systems to report and analyze both errors and near misses. Using the term “incident learning” instead of “event reporting” emphasizes the need to use these experiences to change the practice and make future errors less likely and promote an educational, non-punitive environment. There are challenges in making such a system practical and effective. Speakers from institutions of different sizes and practice environments will share their experiences on how to make such a system work and what benefits their clinics have accrued. Questions that will be addressed include: How to create a system that is easy for front line staff to access How to motivate staff to report How to promote the system as positive and educational and not punitive or demeaning How to organize the team for reviewing and responding to reports How to prioritize which reports to discuss in depth How not to dismiss the rest How to identify underlying causes How to design corrective actions and implement change How to develop useful statistics and analysis tools How to coordinate a departmental system with a larger risk management system How to do this without a dedicated quality manager Some speakers’ experience is with in-house systems and some will share experience with the AAPM/ASTRO national Radiation Oncology Incident Learning System (RO-ILS). Reports intended to be of value nationally need to be comprehensible to outsiders; examples of useful reports will be shown. There will be ample time set

  7. [A case of neonatal lupus syndrome and congenital atrioventricular block associated with maternal antibodies antiRo/SS-A].

    PubMed

    De Leonibus, C; Lembo, C; Giliberti, P; Rojo, S; Foglia, M C; Giordano, L; Fratta, A

    2012-04-01

    The neonatal lupus erythematosus syndrome (LEN) is a disease due to the transplacental passage of maternal antiextractable nuclear antigens (ENA) antibodies, particularly anti-Ro/SS-A and anti-La/SS-B. The disease affects neonates born from mothers with autoimmune diseases. It is characterized by erythematous annular polycylic skin lesions, slightly scaling with prevalent face localization, hematologic and liver diseases and only in 2% of cases with extracutaneous lesions including complete atrioventricular block. The Authors describe a case of LEN characterized by isolated atrioventricular block at birth and endocardial fibroelastosis without skin lesions in a preterm infant female. She was born from asymptomatic, ANA (Anti-Nuclear Antibodies) and ENA (anti-Extractable Nuclear Antigen) positive mother, with a previous miscarriage at the 5th week of gestation.

  8. Application of immersed MF (IMF) followed by reverse osmosis (RO) membrane for wastewater reclamation: A case study in Malaysia.

    PubMed

    Ujang, Z; Ng, K S; Tg Hamzah, Tg Hazmin; Roger, P; Ismail, M R; Shahabudin, S M; Abdul Hamid, M H

    2007-01-01

    A pilot scale membrane plant was constructed and monitored in Shah Alam, Malaysia for municipal wastewater reclamation for industrial application purposes. The aim of this study was to verify its suitability under the local conditions and environmental constraints for secondary wastewater reclamation. Immersed-type crossflow microfiltration (IMF) was selected as the pretreatment step before reverse osmosis filtration. Secondary wastewater after chlorine contact tank was selected as feed water. The results indicated that the membrane system is capable of producing a filtrate meeting the requirements of both WHO drinking water standards and Malaysian Effluent Standard A. With the application of an automatic backwash process, IMF performed well in hydraulic performance with low fouling rate being achieved. The investigations showed also that chemical cleaning is still needed because of some irreversible fouling by microorganisms always remains. RO treatment with IMF pretreatment process was significantly applicable for wastewater reuse purposes and promised good hydraulic performance.

  9. From CoRoT 102899501 to the Sun. A time evolution model of chromospheric activity on the main sequence

    NASA Astrophysics Data System (ADS)

    Gondoin, P.; Gandolfi, D.; Fridlund, M.; Frasca, A.; Guenther, E. W.; Hatzes, A.; Deeg, H. J.; Parviainen, H.; Eigmüller, P.; Deleuil, M.

    2012-12-01

    Aims: The present study reports measurements of the rotation period of a young solar analogue, estimates of its surface coverage by photospheric starspots and of its chromospheric activity level, and derivations of its evolutionary status. Detailed observations of many young solar-type stars, such as the one reported in the present paper, provide insight into rotation and magnetic properties that may have prevailed on the Sun in its early evolution. Methods: Using a model based on the rotational modulation of the visibility of active regions, we analysed the high-accuracy CoRoT lightcurve of the active star CoRoT 102899501. Spectroscopic follow-up observations were used to derive its fundamental parameters. We compared the chromospheric activity level of Corot 102899501 with the R'HK index distribution vs age established on a large sample of solar-type dwarfs in open clusters. We also compared the chromospheric activity level of this young star with a model of chromospheric activity evolution established by combining relationships between the R'HK index and the Rossby number with a recent model of stellar rotation evolution on the main sequence. Results: We measure the spot coverage of the stellar surface as a function of time and find evidence for a tentative increase from 5 - 14% at the beginning of the observing run to 13-29% 35 days later. A high level of magnetic activity on Corot 102899501 is corroborated by a strong emission in the Balmer and Ca ii H and K lines (R'HK ~ -4). The starspots used as tracers of the star rotation constrain the rotation period to 1.625 ± 0.002 days and do not show evidence for differential rotation. The effective temperature (Teff = 5180 ± 80 K), surface gravity (log g = 4.35 ± 0.1), and metallicity ([M/H] = 0.05 ± 0.07 dex) indicate that the object is located near the evolutionary track of a 1.09 ± 0.12 M⊙ pre-main sequence star at an age of 23 ± 10 Myr. This value is consistent with the "gyro-age" of about 8-25 Myr

  10. Quantum Scattering Study of Ro-Vibrational Excitations in N+N(sub 2) Collisions under Re-entry Conditions

    NASA Technical Reports Server (NTRS)

    Wang, Dunyou; Stallcop, James R.; Dateo, Christopher E.; Schwenke, David W.; Huo, Winifred M.

    2004-01-01

    A three-dimensional time-dependent quantum dynamics approach using a recently developed ab initio potential energy surface is applied to study ro-vibrational excitation in N+N2 exchange scattering for collision energies in the range 2.1- 3.2 eV. State-to-state integral exchange cross sections are examined to determine the distribution of excited rotational states of N(sub 2). The results demonstrate that highly-excited rotational states are produced by exchange scattering and furthermore, that the maximum value of (Delta)j increases rapidly with increasing collision energies. Integral exchange cross sections and exchange rate constants for excitation to the lower (upsilon = 0-3) vibrational energy levels are presented as a function of the collision energy. Excited-vibrational-state distributions for temperatures at 2,000 K and 10,000 K are included.

  11. RO1 Funding for Mixed Methods Research: Lessons learned from the Mixed-Method Analysis of Japanese Depression Project

    PubMed Central

    Arnault, Denise Saint; Fetters, Michael D.

    2013-01-01

    Mixed methods research has made significant in-roads in the effort to examine complex health related phenomenon. However, little has been published on the funding of mixed methods research projects. This paper addresses that gap by presenting an example of an NIMH funded project using a mixed methods QUAL-QUAN triangulation design entitled “The Mixed-Method Analysis of Japanese Depression.” We present the Cultural Determinants of Health Seeking model that framed the study, the specific aims, the quantitative and qualitative data sources informing the study, and overview of the mixing of the two studies. Finally, we examine reviewer's comments and our insights related to writing mixed method proposal successful for achieving RO1 level funding. PMID:25419196

  12. VizieR Online Data Catalog: Limb-darkening for CoRoT, Kepler, Spitzer. II. (Claret+, 2013)

    NASA Astrophysics Data System (ADS)

    Claret, A.; Hauschildt, P. H.; Witte, S.

    2013-02-01

    We present an extension of our investigations on limb-darkening coefficients computed with spherical symmetrical PHOENIX models. The models investigated in this paper cover the range 5000K<=Teff<=10000K and complete our previous studies of low effective temperatures computed with the same code. The limb-darkening coefficients are computed for the transmission curves of the Kepler, CoRoT, and Spitzer space missions and the Stroemgren, Johnson-Cousins, Sloan, and 2MASS passbands. These computations were performed by adopting the least-squares method. We have used six laws to describe the specific intensity distribution: linear, quadratic, square root, logarithmic, exponential, and a general law with four terms. The computations are presented for the solar chemical composition and cover the range 3.0<=logg<=5.5. The adopted microturbulent velocity and the mixing-length parameter are 2.0km/s and 2.0. (17 data files).

  13. L’inhalation de corticostéroïdes est-elle sécuritaire durant la grossesse?

    PubMed Central

    Smy, Laura; Chan, Alvin C.H.; Bozzo, Pina; Koren, Gideon

    2014-01-01

    Résumé Question Une femme atteinte d’asthme léger à modéré, autrement en santé, s’est présentée à ma clinique aujourd’hui après avoir appris qu’elle était enceinte. Elle m’a demandé si elle devait continuer à prendre ses corticostéroïdes en inhalation (CSI) et, dans l’affirmative, s’il pourrait y avoir des risques pour son enfant à naître. Quels seraient vos conseils à ce propos? Réponse Compte tenu des données probantes publiées, les CSI devraient être continués durant toute la grossesse à des doses allant de faibles à modérées et suffisantes pour contrôler les symptômes de l’asthme et prévenir les exacerbations. Il faut toutefois être prudent quand il s’agit de doses de plus de 1 000 µg/j (d’équivalent de béclométasone avec chlorofluorocarbures), quoiqu’il soit actuellement questionnable si de telles doses causeraient des effets indésirables. Il faut renseigner de manière continue les patientes sur l’administration appropriée des CSI et l’observance du traitement, y compris durant le premier trimestre. Un bon contrôle de l’asthme réduira la nécessité de doses plus fortes de CSI et de l’exposition possible à des corticostéroïdes systémiques et diminuera ainsi le risque de résultats périnatals ou de grossesse indésirables.

  14. The GTC exoplanet transit spectroscopy survey. III. No asymmetries in the transit of CoRoT-29b

    NASA Astrophysics Data System (ADS)

    Pallé, E.; Chen, G.; Alonso, R.; Nowak, G.; Deeg, H.; Cabrera, J.; Murgas, F.; Parviainen, H.; Nortmann, L.; Hoyer, S.; Prieto-Arranz, J.; Nespral, D.; Cabrera Lavers, A.; Iro, N.

    2016-05-01

    Context. The launch of the exoplanet space missions obtaining exquisite photometry from space has resulted in the discovery of thousands of planetary systems with very different physical properties and architectures. Among them, the exoplanet CoRoT-29b was identified in the light curves the mission obtained in summer 2011, and presented an asymmetric transit light curve, which was tentatively explained via the effects of gravity darkening. Aims: Transits of CoRoT-29b are measured with precision photometry, to characterize the reported asymmetry in their transit shape. Methods: Using the OSIRIS spectrograph at the 10-m GTC telescope, we perform spectro-photometric differential observations, which allow us to both calculate a high-accuracy photometric light curve, and a study of the color-dependence of the transit. Results: After careful data analysis, we find that the previously reported asymmetry is not present in either of two transits, observed in July 2014 and July 2015 with high photometric precisions of 300 ppm over 5 min. Due to the relative faintness of the star, we do not reach the precision necessary to perform transmission spectroscopy of its atmosphere, but we see no signs of color-dependency of the transit depth or duration. Conclusions: We conclude that the previously reported asymmetry may have been a time-dependent phenomenon, which did not occur in more recent epochs. Alternatively, instrumental effects in the discovery data may need to be reconsidered. Light curves are only available at the CDS via anonymous ftp to http://cdsarc.u-strasbg.fr (ftp://130.79.128.5) or via http://cdsarc.u-strasbg.fr/viz-bin/qcat?J/A+A/589/A62

  15. [Determination of heavy metals for RoHS compliance by ICP-OES spectrometry coupled with microwave extraction system].

    PubMed

    Hua, Li; Wu, Yi-Ping; An, Bing; Lai, Xiao-Wei

    2008-11-01

    The harm of heavy metals contained in electronic and electrical equipment (EEE) on environment is of high concern by human. Aiming to handle the great challenge of RoHS compliance, the determinations of trace or ultratrace chromium (Cr), cadmium (Cd), mercury (Hg) and lead (Pb) by inductively coupled plasma optical emission spectrometry (ICP-OES) was performed in the present paper, wherein, microwave extraction technology was used to prepare the sample solutions. In addition, the precision, recovery, repeatability and interference issues of this method were also discussed. The results exhibited that using the microwave extraction system to prepare samples is more quick, lossless, contamination-free in comparison with the conventional extraction methods such as dry ashing, wet-oven extraction etc. By analyzing the recoveries of these four heavy metals over different working time and wavelengths, the good recovery range between 85% and 115% showed that there was only tiny loss or contamination during the process of microwave extraction, sample introduction and ICP detection. Repeatability experiments proved that ICP plasma had a good stability during the working time and the matrix effect was small. Interference was a problem troublesome for atomic absorption spectrometry (AAS), however, the techniques of standard additions or inter-element correction (IEC) method can effectively eliminated the interferences of Ni, As, Fe etc. with the Cd determination. By employing the multi-wavelengths and two correction point methods, the issues of background curve sloping shift and spectra overlap were successfully overcome. Besides, for the determinations of trace heavy metal elements, the relative standard deviation (RSD) was less than 3% and the detection limits were less than 1 microg x L(-10 (3sigma, n = 5) for samples, standard solutions, and standard additions, which proved that ICP-OES has a good precision and high reliability. This provided a reliable technique support

  16. Sequencing of aromatase inhibitors

    PubMed Central

    Bertelli, G

    2005-01-01

    Since the development of the third-generation aromatase inhibitors (AIs), anastrozole, letrozole and exemestane, these agents have been the subject of intensive research to determine their optimal use in advanced breast cancer. Not only have they replaced progestins in second-line therapy and challenged the role of tamoxifen in first-line, but there is also evidence for a lack of cross-resistance between the steroidal and nonsteroidal AIs, meaning that they may be used in sequence to obtain prolonged clinical benefit. Many questions remain, however, as to the best sequence of the two types of AIs and of the other available agents, including tamoxifen and fulvestrant, in different patient groups. PMID:16100523

  17. Effects of (−)-RO363 at human atrial β-adrenoceptor subtypes, the human cloned β3-adrenoceptor and rodent intestinal β3-adrenoceptors

    PubMed Central

    Molenaar, Peter; Sarsero, Doreen; Arch, Jonathan R S; Kelly, John; Henson, Sian M; Kaumann, Alberto J

    1997-01-01

    Chronic treatment of patients with β-blockers causes atrial inotropic hyperresponsiveness through β2-adrenoceptors, 5-HT4 receptors and H2-receptors but apparently not through β1-adrenoceptors despite data claiming an increased β1-adrenoceptor density from homogenate binding studies. We have addressed the question of β1-adrenoceptor sensitivity by determining the inotropic potency and intrinsic activity of the β1-adrenoceptor selective partial agonist (−)-RO363 and by carrying out both homogenate binding and quantitative β-adrenoceptor autoradiography in atria obtained from patients treated or not treated with β-blockers. In the course of the experiments it became apparent that (−)-RO363 also may cause agonistic effects through the third atrial β-adrenoceptor. To assess whether (−)-RO363 also caused agonistic effects through β3-adrenoceptors we studied its relaxant effects in rat colon and guinea-pig ileum, as well as receptor binding and adenylyl cyclase stimulation of chinese hamster ovary (CHO) cells expressing human β3-adrenoceptors. β-Adrenoceptors were labelled with (−)-[125I]-cyanopindolol. The density of both β1- and β2-adrenoceptors was unchanged in the 2 groups, as assessed with both quantitative receptor autoradiography and homogenate binding. The affinities of (−)-RO363 for β1-adrenoceptors (pKi=8.0–7.7) and β2-adrenoceptors (pKi=6.1–5.8) were not significantly different in the two groups. (−)-RO363 increased atrial force with a pEC50 of 8.2 (β-blocker treated) and 8.0 (non-β-blocker treated) and intrinsic activity with respect to (−)-isoprenaline of 0.80 (β-blocker treated) and 0.54 (non-β-blocker treated) (P<0.001) and with respect to Ca2+ (7 mM) of 0.65 (β-blocker treated) and 0.45 (non-β-blocker treated) (P<0.01). The effects of (−)-RO363 were resistant to antagonism by the β2-adrenoceptor antagonist, ICI 118,551 (50 nM). The effects of 0.3–10 nM (−)-RO363 were antagonized by 3–10 nM of the

  18. Effects of (-)-RO363 at human atrial beta-adrenoceptor subtypes, the human cloned beta 3-adrenoceptor and rodent intestinal beta 3-adrenoceptors.

    PubMed

    Molenaar, P; Sarsero, D; Arch, J R; Kelly, J; Henson, S M; Kaumann, A J

    1997-01-01

    1. Chronic treatment of patients with beta-blockers causes atrial inotropic hyperresponsiveness through beta 2-adrenoceptors, 5-HT4 receptors and H2-receptors but apparently not through beta 1-adrenoceptors despite data claiming an increased beta 1-adrenoceptor density from homogenate binding studies. We have addressed the question of beta 1-adrenoceptor sensitivity by determining the inotropic potency and intrinsic activity of the beta 1-adrenoceptor selective partial agonist (-)-RO363 and by carrying out both homogenate binding and quantitative beta-adrenoceptor autoradiography in atria obtained from patients treated or not treated with beta-blockers. In the course of the experiments it became apparent that (-)-RO363 also may cause agonistic effects through the third atrial beta-adrenoceptor. To assess whether (-)-RO363 also caused agonistic effects through beta 3-adrenoceptors we studied its relaxant effects in rat colon and guinea-pig ileum, as well as receptor binding and adenylyl cyclase stimulation of chinese hamster ovary (CHO) cells expressing human beta 3-adrenoceptors. 2. beta-Adrenoceptors were labelled with (-)-[125I]-cyanopindolol. The density of both beta 1- and beta 2-adrenoceptors was unchanged in the 2 groups, as assessed with both quantitative receptor autoradiography and homogenate binding. The affinities of (-)-RO363 for beta 1-adrenoceptors (pKi = 8.0-7.7) and beta 2-adrenoceptors (pKi = 6.1-5.8) were not significantly different in the two groups. 3. (-)-RO363 increased atrial force with a pEC50 of 8.2 (beta-blocker treated) and 8.0 (non-beta-blocker treated) and intrinsic activity with respect to (-)-isoprenaline of 0.80 (beta-blocker treated) and 0.54 (non-beta-blocker treated) (P < 0.001) and with respect to Ca2+ (7 mM) of 0.65 (beta-blocker treated) and 0.45 (non-beta-blocker treated) (P < 0.01). The effects of (-)-RO363 were resistant to antagonism by the beta 2-adrenoceptor antagonist, ICI 118,551 (50 nM). The effects of 0.3-10 nM (-)-RO

  19. RoMEO Studies 8: Self-Archiving: The Logic behind the Colour-Coding Used in the Copyright Knowledge Bank

    ERIC Educational Resources Information Center

    Jenkins, Celia; Probets, Steve; Oppenheim, Charles; Hubbard, Bill

    2007-01-01

    Purpose: The purpose of this research is to show how the self-archiving of journal papers is a major step towards providing open access to research. However, copyright transfer agreements (CTAs) that are signed by an author prior to publication often indicate whether, and in what form, self-archiving is allowed. The SHERPA/RoMEO database enables…

  20. Characterization of resistance to Globodera rostochiensis pathotype Ro1 in cultivated and wild potato species accessions from the Vavilov Institute of Plant Industry

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Potato cyst nematodes (PCN) in Russia are represented by only Globodera rostochiensis pathotype Ro1. It is a quarantine pathogen with losses in yield in susceptible cultivars which can reach 50-90%. The aims of our study were to verify the species and pathotype composition of natural PCN populations...

  1. T cell epitope mimicry between Sjögren's syndrome Antigen A (SSA)/Ro60 and oral, gut, skin and vaginal bacteria.

    PubMed

    Szymula, Agnieszka; Rosenthal, Jacob; Szczerba, Barbara M; Bagavant, Harini; Fu, Shu Man; Deshmukh, Umesh S

    2014-01-01

    This study was undertaken to test the hypothesis that Sjogren's syndrome Antigen A (SSA)/Ro60-reactive T cells are activated by peptides originating from oral and gut bacteria. T cell hybridomas generated from HLA-DR3 transgenic mice recognized 3 regions on Ro60, with core epitopes mapped to amino acids 228-238, 246-256 and 371-381. BLAST analysis identified several mimicry peptides, originating from human oral, intestinal, skin and vaginal bacteria, as well as environmental bacteria. Amongst these, a peptide from the von Willebrand factor type A domain protein (vWFA) from the oral microbe Capnocytophaga ochracea was the most potent activator. Further, Ro60-reactive T cells were activated by recombinant vWFA protein and whole Escherichia coli expressing this protein. These results demonstrate that peptides derived from normal human microbiota can activate Ro60-reactive T cells. Thus, immune responses to commensal microbiota and opportunistic pathogens should be explored as potential triggers for initiating autoimmunity in SLE and Sjögren's syndrome.

  2. In vitro activity of Ro 23-9424, a dual-action antibacterial agent, against bacterial isolates from cancer patients compared with those of other agents.

    PubMed Central

    Rolston, K V; Nguyen, H T; Ho, D H; LeBlanc, B; Bodey, G P

    1992-01-01

    The in vitro activity of Ro 23-9424 against bacterial isolates from patients with cancer was compared with those of fleroxacin, ciprofloxacin, cefoperazone, and ceftazidime. Ro 23-9424 inhibited the majority of the members of the family Enterobacteriaceae and all Aeromonas isolates at a concentration of less than or equal to 1.0 micrograms/ml. It was also active against Acinetobacter spp. and Haemophilus influenzae, including beta-lactamase-producing strains. The MIC for 90% of isolates (MIC90) of Pseudomonas aeruginosa was 16.0 micrograms/ml. All group A and B streptococci were inhibited by less than or equal to 0.25 micrograms/ml, and 90% of group G streptococci and Streptococcus pneumoniae were inhibited by 1.0 micrograms/ml. All methicillin-susceptible strains of Staphylococcus aureus and 60% of methicillin-resistant strains were susceptible to 2.0 micrograms of Ro 23-9424 per ml, whereas the MIC90 for Staphylococcus epidermidis and Staphylococcus hominis isolates was 4.0 micrograms/ml. Staphylococcus haemolyticus and Enterococcus spp. were less susceptible; MIC90s for them were 16.0 and 32.0 micrograms/ml. Ro 23-9424 has a broad antibacterial spectrum and potential utility for therapy of infections in cancer patients. PMID:1503453

  3. Overexpression of RoDELLA impacts the height, branching, and flowering behaviour of Pelargonium × domesticum transgenic plants.

    PubMed

    Hamama, L; Naouar, A; Gala, R; Voisine, L; Pierre, S; Jeauffre, J; Cesbron, D; Leplat, F; Foucher, F; Dorion, N; Hibrand-Saint Oyant, L

    2012-11-01

    KEY MESSAGE : We reported the cloning of a rose DELLA gene. We obtained transgenic Pelargonium lines overexpressing this gene which presented several phenotypes in plant growth, root growth, flowering time and number of inflorescences. Control of development is an important issue for production of ornamental plant. The plant growth regulator, gibberellins (GAs), plays a pivotal role in regulating plant growth and development. DELLA proteins are nuclear negative regulator of GA signalling. Our objective was to study the role of GA in the plant architecture and in the blooming of ornamentals. We cloned a rose DELLA homologous gene, RoDELLA, and studied its function by genetic transformation of pelargonium. Several transgenic pelargonium (Pelargonium × domesticum 'Autum Haze') lines were produced that ectopically expressed RoDELLA under the control of the 35S promoter. These transgenic plants exhibited a range of phenotypes which could be related to the reduction in GA response. Most of transgenic plants showed reduced growth associated to an increase of the node and branch number. Moreover, overexpression of RoDELLA blocked or delayed flowering in transgenic pelargonium and exhibited defects in the root formation. We demonstrated that pelargonium could be used to validate ornamental gene as the rose DELLA gene. RoDELLA overexpression modified many aspects of plant developmental pathways, as the plant growth, the transition of vegetative to floral stage and the ability of rooting.

  4. PAPR reduction and receiver sensitivity improvement in 16QAM-OFDM RoF system using DMT modulation and BTN-PS technique

    NASA Astrophysics Data System (ADS)

    Shao, Yufeng

    2016-03-01

    In this letter, we present the generation, the peak-to average power ratio (PAPR) reduction, the heterodyne detection, the self-mixing reception, and the transmission performance evaluation of 16QAM-OFDM signals in 60 GHz radio over fiber (RoF) system using Discrete multitone (DMT) modulation and Better Than Nyquist pulse shaping (BTN-PS) technique. DMT modulation is introduced in the RoF system, in-phase and quadrature (IQ) will not be required using BTN-PS method, and the computation complexity is much lower than other published techniques for reduced PAPR in the RoF system. In the experiment, 5 Gb/s 16QAM-OFDM downlink signals are transmitted over 42 km SMF-28 and a 0.4 m wireless channel. The experimental results show that the receiver sensitivity is effectively enhanced using this method. Therefore, the introduced BTN-PS technique and its application is a competitive scheme for reducing PAPR, and enhancing the receiver sensitivity in future RoF system.

  5. Regional specific binding of (/sup 11/C)RO 15 1788 to central type benzodiazepine receptors in human brain: quantitative evaluation by PET

    SciTech Connect

    Pappata, S.; Samson, Y.; Chavoix, C.; Prenant, C.; Maziere, M.; Baron, J.C.

    1988-06-01

    The central type benzodiazepine receptors were studied in 17 healthy human subjects with /sup 11/C-RO 15 1788 and positron emission tomography (PET). The brain regional distribution of the tracer in eight control studies performed after injection of trace doses of /sup 11/C-RO 15 1788 was consistent with that of benzodiazepine receptors. Saturation studies with co-injected cold RO 15 1788 in the remaining subjects showed a dose-dependent decrease of brain radiotracer until full inhibition of specific binding was achieved with doses above 0.1 mg/kg (four studies). Based on the results, a simple method to estimate the specifically bound /sup 11/C-RO 15 1788 regionally in a single PET study is proposed, using the data from the full-saturation studies as a stable estimate of the nondisplaceable radioligand concentration. Using this method, it was found that quasiequilibrium between the estimated specifically bound and nondisplaceable components was achieved at times equal to or longer than 20 min after tracer administration. The validity of this method was partly supported by further results, showing a good agreement between the regional specific binding so calculated and postmortem data of receptor density.

  6. The Anxiolytic Etifoxine Binds to TSPO Ro5-4864 Binding Site with Long Residence Time Showing a High Neurosteroidogenic Activity.

    PubMed

    Costa, Barbara; Cavallini, Chiara; Da Pozzo, Eleonora; Taliani, Sabrina; Da Settimo, Federico; Martini, Claudia

    2017-04-04

    The low binding affinity of the approved anxiolytic drug etifoxine (Stresam) at the steroidogenic 18 kDa translocator protein (TSPO) has questioned the specific contribution of this protein in mediating the etifoxine neurosteroidogenic efficacy. Residence time (RT) at the binding site of the classical TSPO ligand PK11195 is emerging as a relevant neurosteroidogenic efficacy measure rather than the binding affinity. Here etifoxine was evaluated for (i) the in vitro neurosteroidogenic activity in comparison to poorly neurosteroidogenic reference TSPO ligands (PK11195 and Ro5-4864) and (ii) the affinity and RT at [(3)H]PK11195 and [(3)H]Ro5-4864 binding sites in rat kidney membranes. Etifoxine shows (i) high neurosteroidogenic efficacy and (ii) low affinity/short RT at the [(3)H]PK11195 site and low affinity/long RT at the [(3)H]Ro5-4864 site, at which etifoxine competitively bound. These findings suggest that the long RT of etifoxine at the Ro5-4864 binding site could account for its high neurosteroidogenic efficacy.

  7. Effects of ginseng rhizome and ginsenoside Ro on testosterone 5α-reductase and hair re-growth in testosterone-treated mice.

    PubMed

    Murata, Kazuya; Takeshita, Fumiaki; Samukawa, Keiichi; Tani, Tadato; Matsuda, Hideaki

    2012-01-01

    This research program on the novel functions of Panax ginseng C. A. Meyer focused on the effects of ginseng rhizome on hair re-growth in androgenetic alopecia. Extracts of red ginseng rhizome showed greater dose-dependent inhibitory effects against testosterone 5α-reductase (5αR) when compared with extracts of the main root. Ginsenoside Ro, the predominant ginsenoside in the rhizome, and ginsenoside Rg(3), a unique ginsenoside in red ginseng, showed inhibitory activity against 5αR with IC(50) values of 259.4 and 86.1 µm, respectively. The rhizome of P. japonicus, which contains larger amounts of ginsenoside Ro, also inhibited 5αR. Topical administration of extracts of red ginseng rhizomes (2 mg/mouse) and ginsenoside Ro (0.2 mg/mouse) to shaved skin inhibited hair re-growth suppression after shaving in the testosterone-treated C57BL/6 mice. These results suggest that red ginseng rhizomes containing both oleanane- and dammarane-type ginsenosides are a promising raw material for cosmetic use. This is the first report that ginsenoside Ro enhances in vivo hair re-growth based on their inhibitory activity against 5αR in the androgenetic alopecia model.

  8. The mapping of the human 52-kD Ro/SSA autoantigen gene to human chromosome II, and its polymorphisms

    SciTech Connect

    Frank, M.B.; Itoh, Kazuko ); Fujisaku, Atsushi ); Pontarotti, P. ); Mattei, M.G. ); Neas, B.R. Univ. of Oklahoma, Oklahoma City )

    1993-01-01

    Autoantibodies to the ribonucleoprotein Ro/SSA occur in nearly half of the patients with systemic lupus erythematosus and are associated with lymphopenia, photosensitive dermatitis, and pulmonary and renal disease, which suggests that they have an immunopathologic role. The majority of Ro/SSA precipitin-positive patients produce serum antibodies that bind to the 60-kD and 52-kD Ro/SSA proteins. The authors previously isolated and determined the nucleotide sequence of a cDNA clone that encodes the 52-kD form of the human Ro/SSA protein. In the present study, they have determined the chromosomal location of the gene by in situ hybridization to the end of the short arm of chromosome 11. Hybridization of portions of the cDNA probe to restriction enzyme-digested DNA indicated the gene is composed of at least three exons. The exon encoding the putative zinc fingers of this protein was found to be distinct from that which encodes the leucine zipper. An RFLP of this gene was identified and is associated with the presence of lupus, primarily in black Americans. 60 refs., 3 figs., 3 tabs.

  9. Sirtuin activators and inhibitors

    PubMed Central

    Villalba, José M.; Alcaín, Francisco J.

    2012-01-01

    Sirtuins 1-7 (SIRT1-7) belong to the third class of deacetylase enzymes, which are dependent on NAD+ for activity. Sirtuins activity is linked to gene repression, metabolic control, apoptosis and cell survival, DNA repair, development, inflammation, neuroprotection and healthy aging. Because sirtuins modulation could have beneficial effects on human diseases there is a growing interest in the discovery of small molecules modifying their activity. We review here those compounds known to activate or inhibit sirtuins, discussing the data that support the use of sirtuin-based therapies. Almost all sirtuin activators have been described only for SIRT1. Resveratrol is a natural compound which activates SIRT1, and may help in the treatment or prevention of obesity, and in preventing tumorigenesis and the aging-related decline in heart function and neuronal loss. Due to its poor bioavailability, reformulated versions of resveratrol with improved bioavailability have been developed (resVida, Longevinex®, SRT501). Molecules that are structurally unrelated to resveratrol (SRT1720, SRT2104, SRT2379, among others) have been also developed to stimulate sirtuin activities more potently than resveratrol. Sirtuin inhibitors with a wide range of core structures have been identified for SIRT1, SIRT2, SIRT3 and SIRT5 (splitomicin, sirtinol, AGK2, cambinol, suramin, tenovin, salermide, among others). SIRT1 inhibition has been proposed in the treatment of cancer, immunodeficiency virus infections, Fragile X mental retardation syndrome and for preventing or treating parasitic diseases, whereas SIRT2 inhibitors might be useful for the treatment of cancer and neurodegenerative diseases. PMID:22730114

  10. Design, optimization, and biological evaluation of novel keto-benzimidazoles as potent and selective inhibitors of phosphodiesterase 10A (PDE10A).

    PubMed

    Hu, Essa; Kunz, Roxanne K; Chen, Ning; Rumfelt, Shannon; Siegmund, Aaron; Andrews, Kristin; Chmait, Samer; Zhao, Sharon; Davis, Carl; Chen, Hang; Lester-Zeiner, Dianna; Ma, Ji; Biorn, Christopher; Shi, Jianxia; Porter, Amy; Treanor, James; Allen, Jennifer R

    2013-11-14

    Our development of PDE10A inhibitors began with an HTS screening hit (1) that exhibited both high p-glycoprotein (P-gp) efflux ratios in rat and human and poor metabolic stability. On the basis of cocrystal structure of 1 in human PDE10A enzyme, we designed a novel keto-benzimidazole 26 with comparable PDE10A potency devoid of efflux liabilities. On target in vivo coverage of PDE10A in rat brain was assessed using our previously reported LC-MS/MS receptor occupancy (RO) technology. Compound 26 achieved 55% RO of PDE10A at 30 mg/kg po and covered PDE10A receptors in rat brain in a dose-dependent manner. Cocrystal structure of 26 in PDE10A confirmed the binding mode of the novel scaffold. Further optimization resulted in the identification of keto-benzimidazole 34, which showed an increased in vivo efficacy of 57% RO in rats at 10 mg/kg po and an improved in vivo rat clearance and oral bioavailability.

  11. Phase I study of the combination of two hypoxic cell radiosensitizers, Ro 03-8799 and SR-2508: toxicity and pharmacokinetics

    SciTech Connect

    Newman, H.F.; Bleehen, N.M.; Workman, P.

    1986-07-01

    The hypoxic cell radiosensitizer Ro 03-8799 produces acute central nervous system toxicity which limits repeated doses of the drug to 0.75 g/m/sup 2/, but peripheral neuropathy does not occur. SR-2508 causes no acute effects at doses greater than 3.0 g/m/sup 2/, but causes peripheral neuropathy at cumulative doses of 30 g/m/sup 2/. By combining maximum tolerated doses of each agent, it may be possible to increase efficacy, but not toxicity. Escalating single doses of Ro 03-8799 and SR-2508 were administered to 10 patients. The drugs were infused together in 50 ml of 0.9% saline over 10 min, beginning at 0.5 g/m/sup 2/ of each agent, and proceeding to a fixed dose of 0.75 g/m/sup 2/ Ro 03-8799 with 0.5, 1.0, 2.0, and 3.0 g/m/sup 2/ SR-2508. Four patients experienced the expected acute syndrome related to Ro 03-8799, but the incidence was not increased by escalating doses of SR-2508, and no peripheral neuropathy was seen. Plasma and urine pharmacokinetic studies showed that no drug interaction occurred. Six patients have been given a 9-dose regime over a 3 week period, using 0.75 g/m/sup 2/ Ro 03-8799 and escalating doses of 0.5, 1.0, and 1.5 g/m2 SR-2508. All exhibited the expected acute side effects related to Ro 03-8799, but with no increase at the higher doses of SR-2508. No other toxicity was seen. Plasma pharmacokinetics performed at the beginning and end of the schedule were similar. Biopsies were taken from six superficial tumors following combined radiosensitizer administration. Mean tumor concentrations over the 30 min following the end of infusion were 30 and 72 micrograms/g for Ro 03-8799 and SR-2508, respectively. These values would be expected to translate into an approximate single dose sensitizer enhancement ratio of 1.5 to 1.6, offering a significant gain over the enhancement possible with the drugs given alone.

  12. Matrix Metalloproteinases and their Inhibitors in Vascular Remodeling and Vascular Disease

    PubMed Central

    Raffetto, Joseph D.; Khalil, Raouf A.

    2008-01-01

    Matrix metalloproteinases (MMPs) are a family of proteolytic enzymes that degrade various components of the extracellular matrix (ECM). Members of the MMP family include collagenases, gelatinases, stromelysins, matrilysins and membrane-type MMPs. ProMMPs are cleaved into active forms that promote degradation of ECM proteins. Also, recent evidence suggests direct or indirect effects of MMPs on ion channels in the endothelium and vascular smooth muscle, and on other mechanisms of vascular relaxation/contraction. Endogenous tissue inhibitors of metalloproteinases (TIMPs) reduce excessive proteolytic ECM degradation by MMPs. The balance between MMPs and TIMPs plays a major role in vascular remodeling, angiogenesis, and the uterine and systemic vasodilation during normal pregnancy. An imbalance in the MMPs/TIMPs activity ratio may underlie the pathogenesis of vascular diseases such as abdominal aortic aneurysm, varicose veins, hypertension and preeclampsia. Downregulation of MMPs using genetic manipulations of endogenous TIMPs, or synthetic pharmacological inhibitors such as BB-94 (Batimastat) and doxycycline, and Ro-28-2653, a more specific inhibitor of gelatinases and membrane type 1-MMP, could be beneficial in reducing the MMP-mediated vascular dysfunction and the progressive vessel wall damage associated with vascular disease. PMID:17678629

  13. Biological abatement of cellulase inhibitors

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Bio-abatement uses a fungus to metabolize and remove fermentation inhibitors. To determine whether bio-abatement could alleviate enzyme inhibitor effects observed in biomass liquors after pretreatment, corn stover at 10% (w/v) solids was pretreated with either dilute acid or liquid hot water. The ...

  14. Authentic HIV-1 integrase inhibitors

    PubMed Central

    Liao, Chenzhong; Marchand, Christophe; Burke, Terrence R; Pommier, Yves; Nicklaus, Marc C

    2010-01-01

    HIV-1 integrase (IN) is indispensable for HIV-1 replication and has become a validated target for developing anti-AIDS agents. In two decades of development of IN inhibition-based anti-HIV therapeutics, a significant number of compounds were identified as IN inhibitors, but only some of them showed antiviral activity. This article reviews a number of patented HIV-1 IN inhibitors, especially those that possess high selectivity for the strand transfer reaction. These compounds generally have a polar coplanar moiety, which is assumed to chelate two magnesium ions in the binding site. Resistance to those compounds, when given to patients, can develop as a result of IN mutations. We refer to those compounds as authentic IN inhibitors. Continued drug development has so far delivered one authentic IN inhibitor to the market (raltegravir in 2007). Current and future attention will be focused on the development of novel authentic IN inhibitors with the goal of overcoming viral resistance. PMID:21426159

  15. Effects of the GluN2B-NMDA receptor antagonist Ro 25-6981 on two types of behavioral flexibility in rats.

    PubMed

    Clark, Emma; Antoniak, Kristen; Feniquito, Alyssandra; Dringenberg, Hans C

    2017-02-15

    Recent evidence has implicated N-methyl-d-aspartate receptors (NMDARs) in several aspects of learning and behavioral flexibility in rodents. Here, we examined the effects of treatment with Ro 25-6981, a selective antagonist of NMDARs containing GluN2B subunits, on two types of behavioral flexibility in rats, spatial reversal learning and set-shifting (spatial vs. motor strategy). To examine spatial reversal learning, rats were trained to swim to a hidden platform in a water maze over four days. On the following day, the platform was moved to a new location in the maze. Administration of Ro 25-6981 (10mg/kg) selectively impaired the early phase of reversal learning, but all rats learned to navigate to the new platform location over 12 trials. To examine set-shifting, independent groups of rats were trained to either swim to a fixed location (spatial strategy) or use a motor response (e.g., "turn left"; motor strategy) to find a hidden escape platform in a cross-shaped water maze apparatus; after task acquisition, rats were trained on the second, novel strategy (set-shift) following treatment with either Ro 25-6981 (10mg/kg) or saline. Administration of Ro 25-6981 had no effect on the ability of rats to perform the set-shift and use the new strategy to locate the escape platform. These results suggest that, in rats, spatial reversal learning, but not set-shifting, is sensitive to Ro-25-6981 treatment. Thus, NMDARs-GluN2B signaling may play a selective role in some forms of behavioral plasticity, particularly for situations involving the updating of information in the spatial domain.

  16. YSOVAR II: Mapping YSO Inner Disk Structure in NGC 2264 with Simultaneous Spitzer and CoRoT Time Series Photometry

    NASA Astrophysics Data System (ADS)

    Stauffer, John; Morales-Calderon, Maria; Rebull, Luisa; Affer, Laura; Alencar, Sylvia; Allen, Lori; Barrado, David; Bouvier, Jerome; Calvet, Nuria; Carey, Sean; Carpenter, John; Ciardi, David; Covey, Kevin; D'Alessio, Paola; Espaillat, Catherine; Favata, Fabio; Flaccomio, Ettore; Forbrich, Jan; Furesz, Gabor; Hartman, Lee; Herbst, William; Hillenbrand, Lynne; Holtzman, Jon; Hora, Joe; Marchis, Franck; McCaughrean, Mark; Micela, Giusi; Mundt, Reinhard; Plavchan, Peter; Turner, Neal; Skrutzkie, Mike; Smith, Howard; Song, Inseok; Szentgyorgi, Andy; Terebey, Susan; Vrba, Fred; Wasserman, Lawrence; Watson, Alan; Whitney, Barbara; Winston, Elaine; Wood, Kenny

    2011-05-01

    We propose a simultaneous, continuous 30 day observation of the star forming region NGC2264 with Spitzer and CoRoT. NGC2264 is the only nearby, rich star-forming region which can be observed with CoRoT; it is by definition then the only nearby, rich star-forming region where a simultaneous Spitzer/CoRoT campaign is possible. Fortunately, the visibility windows for the two spacecraft overlap, allowing this program to be done in the Nov. 25, 2011 to Jan. 4, 2012 time period. For 10 days, we propose to map the majority of the cluster (a 35'x35' region) to a depth of 48 seconds per point, with each epoch taking 1.7 hours, allowing of order 12 epochs per day. For the other 20 days, we propose to obtaining staring-mode data for two positions in the cluster having a high density of cluster members. We also plan to propose for a variety of other ground and space-based data, most of which would also be simultaneous with the Spitzer and CoRoT observing. These data will allow us to address many astrophysical questions related to the structure and evolution of the disks of young stars and the interaction of those disks with the forming star. The data may also help inform models of planet formation since planets form and migrate through the pre-main sequence disks during the 0.5-5 Myr age range of stars in NGC2264. The data we collect will also provide an archive of the variability properties of young stars that is unmatched in its accuracy, sensitivity, cadence and duration and which therefore could inspire investigation of phenomena which we cannot now imagine. The CoRoT observations have been approved, contingent on approval of a simultaneous Spitzer observing program (this proposal).

  17. Induction of in vitro heart block is not restricted to affinity purified anti-52 kDa Ro/SSA antibody from mothers of children with neonatal lupus.

    PubMed

    Viana, V S; Garcia, S; Nascimento, J H; Elkon, K B; Brot, N; Campos de Carvalho, A C; Bonfá, E

    1998-01-01

    The ability of affinity purified anti-52 kDa Ro/SSA antibody from patients without obstetric history of neonatal lupus to cause heart block using an experimental model was investigated. IgG-enriched fractions from sera of 20 systemic lupus erythematosus (SLE) and one Sjögren's syndrome (SS) all positives for anti-Ro/SSA antibodies as detected by CIE, were perfused on isolated whole rabbit hearts. Only six (29%) samples induced A-V block, five of them presenting low anti-Ro/SSA titre. All of them recognized the 52 kDa isoform on ELISA whereas only one had a concomitant binding to the 60 kDa protein. Moreover, affinity purified antibodies from two sera previously known to induce A-V block were obtained by affinity chromatography using a column containing the full-length 52 kDa Ro/SSA fusion protein. Paired eluate and effluent devoid of anti-52 kDa activity from the same patient were individually perfused in whole hearts. The ability to cause cardiac blockade was restricted to the affinity anti-52 kDa eluates. In addition, anti-52 kDa eluates from three IgG fractions that primarily failed to induce blockade remained ineffective. The present study has added to our knowledge that affinity anti-52 kDa Ro/SSA antibodies from mothers with healthy infants are capable of causing in vitro cardiac conduction disturbances. A prospective follow up of these patients will better delineate the clinical usefulness of this experimental model.

  18. Formes d'astéroïdes et formation de satellites : rôle de la réaccumulation gravitationnelle

    NASA Astrophysics Data System (ADS)

    Consigli, Jean-François; Tanga, Paolo; Comito, Carlo; Hestroffer, Daniel; Richardson, Derek C.

    2007-04-01

    Plusieurs indices suggèrent qu'un grand nombre d'astéroïdes seraient des empilements de gravats, liés uniquement par gravité et quasiment dépourvus de cohésion interne. Leur formation serait due à la réaccumulation de fragments issus de la destruction antérieure d'un corps parent. La forme de ces objets, que l'on observe, pourrait ainsi être liée à ce processus de réaccumulation gravitationnelle. Toutefois, à l'heure actuelle, on ignore si les formes observées des astéroïdes sont le résultat de la seule réaccumulation ou d'événements ultérieurs entrainant un réajustement de la forme du corps. Dans cette Note, nous nous interrogeons sur l'origine des formes des astéroïdes. A l'aide d'une étude numérique de la réaccumulation, nous étudions les formes d'équilibres possibles correspondants aux modèles théoriques. Les résultats montrent, pour la première fois, que seulement une catégorie précise de formes (sphéroïdes aplatis) est apparemment crée via ce mécanisme. Ces résultats pourraient ainsi fournir d'interessantes contraintes sur l'évolution des formes d'astéroïdes, notamment pour ceux possédant un, ou plusieurs, satellites. Pour citer cet article : J.-F. Consigli et al., C. R. Physique 8 (2007).

  19. A 0.8-2.4 μm Transmission spectrum of the hot Jupiter CoRoT-1b

    SciTech Connect

    Schlawin, E.; Herter, T.; Zhao, M.; Teske, J. K.

    2014-03-01

    Hot Jupiters with brightness temperatures ≳2000 K can have TiO and VO molecules as gaseous species in their atmospheres. The TiO and VO molecules can potentially induce temperature inversions in hot Jupiter atmospheres and also have an observable signature of large optical to infrared transit depth ratios. Previous transmission spectra of very hot Jupiters have shown a lack of TiO and VO, but only in planets that also appear to lack temperature inversions. We measure the transmission spectrum of CoRoT-1b, a hot Jupiter that was predicted to have a temperature inversion potentially due to significant TiO and VO in its atmosphere. We employ the multi-object spectroscopy method using the SpeX and MORIS instruments on the Infrared Telescope Facility (IRTF) and the Gaussian process method to model red noise. By using a simultaneous reference star on the slit for calibration and a wide slit to minimize slit losses, we achieve transit depth precision of 0.03%-0.09%, comparable to the atmospheric scale height but detect no statistically significant molecular features. We combine our IRTF data with optical CoRoT transmission measurements to search for differences in the optical and near-infrared absorption that would arise from TiO/VO. Our IRTF spectrum and the CoRoT photometry disfavor a TiO/VO-rich spectrum for CoRoT-1b, suggesting that the atmosphere has another absorber that could create a temperature inversion or that the blackbody-like emission from the planet is due to a spectroscopically flat cloud, dust, or haze layer that smoothes out molecular features in both CoRoT-1b's emission and transmission spectra. This system represents the faintest planet hosting star (K = 12.2) with a measured planetary transmission spectrum.

  20. The 1.8-A crystal structure of a matrix metalloproteinase 8-barbiturate inhibitor complex reveals a previously unobserved mechanism for collagenase substrate recognition.

    PubMed

    Brandstetter, H; Grams, F; Glitz, D; Lang, A; Huber, R; Bode, W; Krell, H W; Engh, R A

    2001-05-18

    The individual zinc endoproteinases of the tissue degrading matrix metalloproteinase (MMP) family share a common catalytic architecture but are differentiated with respect to substrate specificity, localization, and activation. Variation in domain structure and more subtle structural differences control their characteristic specificity profiles for substrates from among four distinct classes (Nagase, H., and Woessner, J. F. J. (1999) J. Biol. Chem. 274, 21491-21494). Exploitation of these differences may be decisive for the design of anticancer or other drugs, which should be highly selective for their particular MMP targets. Based on the 1.8-A crystal structure of human neutrophil collagenase (MMP-8) in complex with an active site-directed inhibitor (RO200-1770), we identify and describe new structural determinants for substrate and inhibitor recognition in addition to the primary substrate recognition sites. RO200-1770 induces a major rearrangement at a position relevant to substrate recognition near the MMP-8 active site (Ala206-Asn218). In stromelysin (MMP-3), competing stabilizing interactions at the analogous segment hinder a similar rearrangement, consistent with kinetic profiling of several MMPs. Despite the apparent dissimilarity of the inhibitors, the central 2-hydroxypyrimidine-4,6-dione (barbiturate) ring of the inhibitor RO200-1770 mimics the interactions of the hydroxamate-derived inhibitor batimastat (Grams, F., Reinemer, P., Powers, J. C., Kleine, T., Pieper, M., Tschesche, H., Huber, R., and Bode, W. (1995) Eur. J. Biochem. 228, 830-841) for binding to MMP-8. The two additional phenyl and piperidyl ring substituents of the inhibitor bind into the S1' and S2' pockets of MMP-8, respectively. The crystal lattice contains a hydrogen bond between the O(gamma) group of Ser209 and N(delta)1 of His207 of a symmetry related molecule; this interaction suggests a model for recognition of hydroxyprolines present in physiological substrates. We also identify a

  1. Different action of a specific NR2B/NMDA antagonist Ro 25-6981 on cortical evoked potentials and epileptic afterdischarges in immature rats.

    PubMed

    Szczurowska, Ewa; Mareš, Pavel

    2015-02-01

    Ro 25-6981 maleate is a highly selective and activity-dependent antagonist of NMDA ionotropic glutamate receptors containing NR2B subunit (NR2B/NMDARs). The aim of our study was to investigate the influence of Ro 25-6981 administration in developing rats on physiological (single and paired pulse cortical interhemispheric evoked potentials) and epileptic brain activity (cortical afterdischarges (ADs)). Electrophysiological experiments were performed in animals with epidurally implanted electrodes at postnatal days (P) P12, P18, and P25. The drug was injected intraperitoneally at a dose of 1 or 3mg/kg. Control animals were injected with saline (1ml/kg). Single interhemispheric responses were evoked with 0.5-ms biphasic pulses with intensities increasing from 0.4 to 5mA, paired-pulse responses were elicited by twofold threshold intensity. The ADs were elicited by series of 15-s of 1-ms pulses at 8-Hz frequency. Firstly, six stimulations with stable suprathreshold intensity repeated at 30-min intervals were used to determine the time course of Ro 25-6981 effects against ADs in P12 animals. Secondly, similar experiment was performed in all age groups of animals but with 20-min intervals as well as a further experiment using stimulations with stepwise intensities increasing at 10-min intervals from 0.2 to 15 mA. Pretreatment with the 3-mg/kg (but not the lower) dose of Ro 25-9681 decreased significantly the amplitude of single responses evoked with higher stimulation intensities in P12 and P18 animals. Both doses affected responses in P25 animals, only the 1-mg/kg dose was more efficacious than the 3-mg/kg one. Paired pulse responses were not affected by either dose of Ro 25-6981 in any age group. Ro 25-9681 clearly influenced the duration of ADs only in P12 animals. The 1-mg/kg dose did not change the duration of ADs whereas the 3-mg/kg dose suppressed progressive prolongation of ADs with repeated stimulations. This effect was seen even 110-min after the drug injection

  2. The γ Doradus CoRoT target HD 49434. I. Results from the ground-based campaign

    NASA Astrophysics Data System (ADS)

    Uytterhoeven, K.; Mathias, P.; Poretti, E.; Rainer, M.; Martín-Ruiz, S.; Rodríguez, E.; Amado, P. J.; Le Contel, D.; Jankov, S.; Niemczura, E.; Pollard, K. R.; Brunsden, E.; Paparó, M.; Costa, V.; Valtier, J.-C.; Garrido, R.; Suárez, J. C.; Kilmartin, P. M.; Chapellier, E.; Rodríguez-López, C.; Marin, A. J.; Aceituno, F. J.; Casanova, V.; Rolland, A.; Olivares, I.

    2008-10-01

    Context: We present an extensive ground-based photometric and spectroscopic campaign of the γ Dor CoRoT target HD 49434. This campaign was a preparatory step of the CoRoT satellite observations, which occurred between October 2007 and March 2008. Aims: With satellite data, detection of low-degree pulsation modes only is achievable, and, as no filters are available, with poor identification. Ground-based data promise eventually to identify additional modes and provide extra input for the identification: spectroscopic data allows the detection of high-degree modes and an estimate of the azimuthal number m. We attempt to detect and identify as many pulsation modes as possible from the ground-based dataset of the γ Dor star HD 49434, and anticipate the CoRoT results. Methods: We searched for frequencies in the multi-colour variations, the pixel-to-pixel variations across the line profiles, and the moments variations in a large dataset, consisting of both multi-colour photometric and spectroscopic data from different observatories, using different frequency analysis methods. We performed a tentative mode identification of the spectroscopic frequencies using the Moment Method and the Intensity Period Search Method. We also completed an abundance analysis. Results: The frequency analysis clearly indicates the presence of four frequencies in the 0.2-1.7 d-1 interval, as well as six frequencies in the 5-12 d-1 domain. The low frequencies are typical of γ Dor variables, while the high frequencies are common to δ Sct pulsators. We propose that the frequency 2.666 d-1 is the rotational frequency. All modes, for which an identification was possible, appear to be high-degree modes (3 ≤ ell ≤ 8). We did not find evidence for a possible binary nature of the star HD 49434. The element abundances that we derived are consistent with values obtained in previous analyses. Conclusions: We classify the γ Dor star HD 49434 as a hybrid pulsator, which pulsates simultaneously in p

  3. Characterizing ultrafine particle growth at a pine forest site influenced by anthropogenic pollution during BEACHON-RoMBAS-2011

    NASA Astrophysics Data System (ADS)

    Cui, Y.; Hodzic, A.; Smith, J. N.; Ortega, J. V.; de Foy, B.

    2013-12-01

    Representing the formation and growth of ultrafine particles in chemistry and climate models is challenging due to the complexity of processes involved, which leads to uncertainties in aerosol size distributions and their effects on Cloud Condensation Nuclei (CCN). The Rocky Mountain Biogenic Aerosol Study (RoMBAS) was an intensive measurement campaign as part of the broader BEACHON (Bio-hydro-atmosphere interactions of Energy Aerosols, Carbon, H2O, Organics and Nitrogen) project. This took place during July - August 2011 at the Manitou Experimental Forest Observatory. The location is situated in the rural-urban interface along the Colorado Front Range and allows us to study the effects of aerosol formation and other atmospheric chemistry phenomenon in a forested region with periodic urban influences. Surface measurements of gases, aerosols and meteorological parameters from this campaign were used to examine the formation and growth processes leading to observed Aiken-mode Particle burst Events (APEs), and to quantify their effects on aerosol properties and cloud condensation nuclei CCN concentrations. Results suggest that APEs were observed at the forest site in the early afternoon associated with the arrival of anthropogenic plumes from Denver and Colorado Springs. Mean number concentrations of ultrafine particles (4-30nm) typically exceeded 5000 cm-3 during APEs and these elevated concentrations were correlated with elevated SO2. The Weather Research and Forecasting model with on-line Chemistry (WRF-Chem) was used to model APEs during BEACHON-RoMBAS. The model was updated to include an activation nucleation (AN) scheme with an empirical representation of aerosol nucleation rate, and subsequent growth due to the condensation of organic and inorganic vapors. Comparisons with ground measurements show that the updated model reasonably captures aerosol number concentrations and size distribution during APEs, as well as CN and CCN concentrations. Model results

  4. LIF instrument for airborne measurements of OH, HO2 and RO2 radicals in the upper troposphere

    NASA Astrophysics Data System (ADS)

    Broch, S.; Künstler, C.; Bachner, M.; Dahlhoff, K.; Holland, F.; Bayer, N.; Fuchs, H.; Hofzumahaus, A.; Jansen, P.; Wolters, J.; Zöger, M.; Wahner, A.

    2015-12-01

    We present the development and first deployment of a new instrument for the measurement of OH, HO2 and RO2 radicals in the upper troposphere aboard the German research aircraft HALO (High Altitude and LOng range). The instrument is based on the well-established laser induced fluorescence (LIF) technique (Holland et al., 2003; Fuchs et al., 2008). It has two separate measurement cells, one for the direct detection of OH (OH channel) and one for alternating measurements of HO2 and RO2 radicals (ROx channel) after chemical conversion to OH by the reaction with NO. For its deployment on HALO, a Gulfstream-V aircraft, a special air inlet for the OH channel was developed and built at Forschungszentrum Jülich. It is based on the shrouded-inlet design by Eisele et al. (1995) and allows for a controlled reduction of the air flow velocity prior to sampling as well as the performance of inflight calibrations. There is no special inlet system for the ROx channel. It samples directly from the fast airflow along the aircraft. In contrast to our ground based instrument, longer inlet tubes are required to bring the ambient air into the detection cells inside the aircraft. The inflight calibration unit of the OH inlet allows for monitoring relative changes of the OH detection sensitivity with height. Ambient water vapor is photolysed at 185 nm upstream of the inlet nozzle to produce an additional OH signal which can be evaluated by using measurements of water vapor mixing ratio, lamp intensity, and airflow velocity. Due to the very small water vapor mixing ratios in the UTLS region this technique is limited to altitudes up to 11 km. We will give an overview of the technical concept and instrumental setup for the application on HALO. We will show results from laboratory characterization measurements concerning the radical detection sensitivities and first results from flights performed during the OMO-Asia campaign in summer 2015. Literature: Holland et al., J. Geophys. Res., 108

  5. Membrane fouling and anti-fouling strategies using RO retentate from a municipal water recycling plant as the feed for osmotic power generation.

    PubMed

    Chen, Si Cong; Amy, Gary L; Chung, Tai-Shung

    2016-01-01

    RO retentate from a municipal water recycling plant is considered as a potential feed stream for osmotic power generation in this paper. The feasibility of using RO retentate from a municipal water recycling plant was examined from two aspects: (a) the membrane fouling propensity of RO retentate, and (b) the efficacy of anti-fouling strategies. The membranes used in this study were the inner selective thin film composite polyethersulfone (TFC/PES) hollow fiber membranes, which possessed a high water permeability and good mechanical strength. Scaling by phosphate salts was found to be one possible inorganic fouling on the innermost layer of the PES membrane, whereas silica fouling was observed to be the governing fouling on the outmost surface of the PES membrane. Two anti-fouling pretreatments, i.e., pH adjustment and anti-scalant pre-treatment for the feed stream, were studied and found to be straightforward and effective. Using RO retentate at pH 7.2 as the feed and 1 M NaCl as the draw solution, the average power density was 7.3 W/m(2) at 20 bar. The average power density increased to 12.6 W/m(2) by modifying RO retentate with an initial pH value of 5.5 using HCl and to 13.4 W/m(2) by adding 1.1 mM ethylenediaminetetraacetic acid (EDTA). Moreover, the flux recovery of the fouled membranes, without the indicated pretreatments, reached 84.9% using deionized (DI) water flushing and 95.0% using air bubbling under a high crossflow velocity of 23.3 cm/s (Re = 2497) for 30 min. After pretreatment by pH adjustment, the flux recovery increased to 94.6% by DI water flushing and 100.0% by air bubbling. After pretreatment by adding 1.1 mM EDTA into RO retentate, flux was almost fully restored by physical cleaning by DI water flushing and air bubbling. These results provide insight into developing an effective pretreatment by either pH adjustment or EDTA addition before PRO and physical cleaning methods by DI water flushing and air bubbling for membrane used in

  6. Differential effects of protein kinase C inhibitors on chemokine production in human synovial fibroblasts.

    PubMed Central

    Jordan, N. J.; Watson, M. L.; Yoshimura, T.; Westwick, J.

    1996-01-01

    1. Rheumatoid arthritis is associated with the accumulation and activation of selected populations of inflammatory cells within the arthritic joint. One putative signal for this process is the production, by resident cells, of a group of inflammatory mediators known as the chemokines. 2. The chemokines interleukin-8 (IL-8), monocyte chemotactic protein-1 (MCP-1) and RANTES (regulated on activation normal T-cell expressed and presumably secreted) are target-cell specific chemoattractants produced by synovial fibroblasts in response to stimulation with interleukin-1 alpha (IL-1 alpha) or tumour necrosis factor alpha (TNF alpha). The signalling pathways involved in their production are not well defined. We therefore used four different protein kinase C inhibitors to investigate the role of this kinase in the regulation of chemokine mRNA and protein expression in human cultured synovial fibroblasts. 3. The non-selective PKC inhibitor, staurosporine (1-300 nM) significantly increased the production of IL-1 alpha-induced IL-8 mRNA and protein. A specific PKC inhibitor, chelerythrine chloride (0.1-3 microM), also caused a small concentration-dependent increase in IL-8 mRNA and protein production. In contrast, 3-[1-[3-(amidinothio)propyl]-3-indoly]-4-(1-methyl-3-indolyl )- 1H-pyrrole-2,5-dione methanesulphonate (Ro 31-8220) and 2[1-(3-dimethylaminopropyl)-1H-indol-3-yl]-3-(1H-indol-3- yl)-maleimide (GF 109203X), two selective PKC inhibitors of the substituted bisindolylmaleimide family had a concentration-dependent biphasic effect on IL-1 alpha or TNF alpha-induced chemokine expression. At low concentrations they caused a stimulation in chemokine production, which was especially evident at the mRNA level. At higher concentrations both inhibited IL-1 alpha or TNF alpha-induced chemokine mRNA and protein production. Ro 31-8220 was 10 fold more potent than GF 109203X, with an IC50 of 1.6 +/- 0.08 microM (mean +/- s.e.mean, n = 4) for IL-1 alpha induced IL-8 production. Ro 31

  7. [ACE inhibitors and the kidney].

    PubMed

    Hörl, W H

    1996-01-01

    Treatment with ACE inhibitors results in kidney protection due to reduction of systemic blood pressure, intraglomerular pressure, an antiproliferative effect, reduction of proteinuria and a lipid-lowering effect in proteinuric patients (secondary due to reduction of protein excretion). Elderly patients with diabetes melitus, coronary heart disease or peripheral vascular occlusion are at risk for deterioration of kidney function due to a high frequency of renal artery stenosis in these patients. In patients with renal insufficiency dose reduction of ACE inhibitors is necessary (exception: fosinopril) but more important is the risk for development of hyperkalemia. Patients at risk for renal artery stenosis and patients pretreated with diuretics should receive a low ACE inhibitor dosage initially ("start low - go slow"). For compliance reasons once daily ACE inhibitor dosage is recommended.

  8. Selective Inhibitors of Protein Methyltransferases

    PubMed Central

    2015-01-01

    Mounting evidence suggests that protein methyltransferases (PMTs), which catalyze methylation of histone and nonhistone proteins, play a crucial role in diverse biological processes and human diseases. In particular, PMTs have been recognized as major players in regulating gene expression and chromatin state. PMTs are divided into two categories: protein lysine methyltransferases (PKMTs) and protein arginine methyltransferases (PRMTs). There has been a steadily growing interest in these enzymes as potential therapeutic targets and therefore discovery of PMT inhibitors has also been pursued increasingly over the past decade. Here, we present a perspective on selective, small-molecule inhibitors of PMTs with an emphasis on their discovery, characterization, and applicability as chemical tools for deciphering the target PMTs’ physiological functions and involvement in human diseases. We highlight the current state of PMT inhibitors and discuss future directions and opportunities for PMT inhibitor discovery. PMID:25406853

  9. Inhibitors of pig kidney trehalase.

    PubMed

    Kyosseva, S V; Kyossev, Z N; Elbein, A D

    1995-02-01

    Trehazolin, a new trehalase inhibitor isolated from the culture broth of Micromonospora, was reported to be a highly specific inhibitor for porcine and silk worm trehalases with IC50 values of 5.5 x 10(-9) and 3.7 x 10(-9) M, respectively (O. Ando, H. Satake, K. Itoi, A. Sato, M. Nakajima, S. Takashi, H. Haruyama, Y. Ohkuma, T. Kinoshita, and R. Enokita (1991) J. Antibiot. 44, 1165-1168). We also found that trehazolin is a very powerful and quite specific inhibitor against purified pig kidney trehalase, giving an IC50 value of 1.9 x 10(-8) M. Lineweaver-Burk plots showed that this compound was a competitive inhibitor of the trehalase. However, even at concentrations of 200 micrograms/ml, trehazolin did not inhibit the rat intestinal maltase or sucrase, yeast alpha-glucosidase or almond beta-glucosidase. Validoxylamine A and validamycin A, two other trehalase inhibitors, showed potent competitive inhibition against purified pig kidney trehalase, with IC50 values of 2.4 x 10(-9) and 2.5 x 10(-4) M, respectively. On the other hand, validoxylamine A was almost inactive against rat intestinal sucrase and maltase, with some inhibition being observed at millimolar concentration. A number of other glucosidase inhibitors, such as MDL 25637, castanospermine, and deoxynojirimycin were also tested against the purified trehalase and showed reasonable inhibitory activity.

  10. Complex formation of peptide antibiotic Ro09-0198 with lysophosphatidylethanolamine: sup 1 H NMR analyses of dimethyl sulfoxide solution

    SciTech Connect

    Wakamatsu, Kaori; Choung, Seyoung; Kobayashi, Tetsuyuki; Inoue, Keizo; Higashijima, Tsutomu ); Miyazawa, Tatsuo )

    1990-01-09

    Ro09-0198 is a peptide antibiotic and immunopotentiator produced by Streptoverticillium griseoverticillatum which exhibits antitumor and antimicrobial activities. The chemical structure has been determined. This peptide specifically interacts with (lyso)phosphatidylethanolamine, causing hemolysis and enhancing permeability in phosphatidylethanolamine-containing vesicles. The highly specific nature of the interaction was studied by two dimensional proton NMR analyses. Proton resonances of the peptide were observed in dimethyl sulfoxide solution in the presence of 1-dodecanoyl-sn-glycerophosphoethanolamine. By comparison to the chemical shifts in the absence of lysophosphatidylethanolamine and by analysis of intermolecular cross-peaks in NOESY spectra, amino acid residues involved in the binding with the phospholipid were identified. The ammonium group of the phospholipid interacts with the carboxylate group of {beta}-hydroxyaspartic acid-15 but not with that of the carboxylate terminus. The secondary ammonium group of lysinoalanine-19/6 is probably bound to the phosphate group of the lipid. The peptide does not interact strongly with the fatty acid chain of the lipid. A folded structure of the central part (from Phe{sup 7} to Ala(S){sup 14}) of the peptide opens on binding with the phospholipid and accommodates the glycerophoethanolamine head group.

  11. Thermal maturity patterns in the Ordovician and Devonian of Pennsylvania using conodont color alteration index (CAI) and vitrinite reflectance (%Ro)

    USGS Publications Warehouse

    Repetski, J.E.; Ryder, R.T.; Harper, J.A.; Trippi, M.H.

    2006-01-01

    This new series of maps enhances previous thermal maturity maps in Pennsylvania by establishing: 1) new subsurface CAI data points for the Ordovician and Devonian and 2) new %Ro and Rock Eval subsurface data points for Middle and Upper Devonian black shale units. Thermal maturity values for the Ordovician and Devonian strata are of major interest because they contain the source rocks for most of the oil and natural gas resources in the basin. Thermal maturity patterns of the Middle Ordovician Trenton Group are evaluated here because they closely approximate those of the overlying Ordovician Utica Shale that is believed to be the source rock for the regional oil and gas accumulation in Lower Silurian sandstones and for natural gas fields in fractured dolomite reservoirs of the Ordovician Black River-Trenton Limestones. Improved CAI-based thermal maturity maps of the Ordovician are important to identify areas of optimum gas generation from the Utica Shale and to provide constraints for interpreting the origin of oil and gas in the Lower Silurian regional accumulation and Ordovician Black River-Trenton fields. Thermal maturity maps of the Devonian will better constrain burial history-petroleum generation models of the Utica Shale, as well as place limitations on the origin of regional oil and gas accumulations in Upper Devonian sandstone and Middle to Upper Devonian black shale.

  12. Temporal behavior of the SO 1.707 μm ro-vibronic emission band in Io's atmosphere

    NASA Astrophysics Data System (ADS)

    Laver, Conor; de Pater, Imke; Roe, Henry; Strobel, Darrell F.

    2007-08-01

    We report observations of the ro-vibronic aΔ→XΣ transition of SO at 1.707 μm on Io. These data were taken while Io was eclipsed by Jupiter, on four nights between July 2000 and March 2003. We analyze these results in conjunction with a previously published night to investigate the temporal behavior of these emissions. The observations were all conducted using the near-infrared spectrometer NIRSPEC on the W.M. Keck II telescope. The integrated emitted intensity for this band varies from 0.8×10 to 2.4×10 photons/s, with a possible link to variations in Loki's infrared brightness. The band-shapes imply rotational temperatures of 550-1000 K for the emitting gas, lending further evidence to a volcanic origin for sulfur monoxide. An attempt to detect the BΣ→XΣ transition of SO at 0.97 μm was unsuccessful; simultaneous detection with the 1.707 μm band would permit determination of the SO column abundance.

  13. VizieR Online Data Catalog: Limb-darkening for CoRoT, Kepler, Spitzer (Claret+, 2012)

    NASA Astrophysics Data System (ADS)

    Claret, A.; Hauschildt, P. H.; Witte, S.

    2012-09-01

    The knowledge of how the specific intensity is distributed over the stellar disk is crucial for interpreting the light curves of extrasolar transiting planets, double-lined eclipsing binaries, and other astrophysical phenomena. To provide theoretical inputs for light curve modelling codes, we present new calculations of limb-darkening coefficients for the spherically symmetric PHOENIX models. The limb-darkening coefficients were computed by covering the transmission curves of Kepler, CoRoT, and Spitzer space missions, as well as the passbands of the Stromgren, Johnson-Cousins, Sloan, and 2MASS. These computations adopted the least-square method. In addition, we also calculated the linear and bi-parametric approximations by adopting the flux conservation method as an additional tool for estimating the theoretical error bars in the limb-darkening coefficients. Six laws were used to describe the specific intensity distribution: linear, quadratic, square root, logarithmic, exponential, and a more general one with 4 terms. The computations are presented for the solar chemical composition, with logg varying between 2.5 and 5.5 and effective temperatures between 1500K-4800K. The adopted Microturbulent velocity and the mixing-length parameters are 2.0km/s and 2.0, respectively. Model are for solar metallicity. (17 data files).

  14. Thermal maturity patterns (CAI and %Ro) in the Ordovician and Devonian rocks of the Appalachian basin in West Virginia

    USGS Publications Warehouse

    Repetski, John E.; Ryder, Robert T.; Avary, Katharine Lee; Trippi, Michael H.

    2005-01-01

    The objective of this study is to enhance existing thermal maturity maps in West Virginia by establishing: 1) new subsurface CAI data points for the Ordovician and Devonian and 2) new %Ro and Rock Eval subsurface data points for Middle and Upper Devonian black shale units. Thermal maturity values for the Ordovician and Devonian strata are of major interest because they contain the source rocks for most of the oil and natural gas resources in the basin. Thermal maturity patterns of the Middle Ordovician Trenton Limestone are evaluated here because they closely approximate those of the overlying Ordovician Utica Shale that is believed to be the source rock for the regional oil and gas accumulation in Lower Silurian sandstones (Ryder and others, 1998) and for natural gas fields in fractured dolomite reservoirs of the Ordovician Black River-Trenton Limestones. Improved CAI-based thermal maturity maps of the Ordovician are important to identify areas of optimum gas generation from the Utica Shale and to provide constraints for interpreting the origin of oil and gas in the Lower Silurian regional accumulation and Ordovician Black River-Trenton fields. Thermal maturity maps of the Devonian will better constrain burial history-petroleum generation models of the Utica Shale, as well as place limitations on the origin of regional oil and gas accumulations in Upper Devonian sandstone and Middle to Upper Devonian black shale.

  15. Polarization multiplexing of two MIMO RoF signals and one baseband signal over a single wavelength

    NASA Astrophysics Data System (ADS)

    Elmagzoub, M. A.; Bakar Mohammad, Abu; Shaddad, Redhwan Q.; Al-Gailani, Samir A.

    2016-01-01

    Next-generation (NG) access networks require simultaneous provision of wired and wireless services and high data rates to meet the large demands of mobility and multiple services. In this paper, we propose a novel spectral efficient radio over fiber (RoF) scheme to simultaneously provide two spatially multiplexed multiple input multiple output (MIMO) wireless signals with a baseband (BB) wired signal in one wavelength using a centralized light source. The proposed scheme can be applicable to wavelength division multiplexed passive optical networks (WDM-PONs). The BB signal is modulated at a low extinction ratio (ER). The modulated light is re-used to modulate two MIMO signals that have the same carrier frequency that is combined optically using polarization-division-multiplexing (PDM). The data rate for each MIMO stream was 1.25 Gb/s, and the data rate was 2.5 Gb/s for the BB signal. Error free performance with a bit error rate (BER) of 10-9 was achieved for all three signals after 20 km and 60 km through single mode fiber (SMF) for 16-QAM and 4-QAM for the MIMO signals, respectively.

  16. Chronic treatment with the monoamine oxidase inhibitors clorgyline and pargyline down-regulates non-adrenoceptor [3H]-idazoxan binding sites in the rat brain.

    PubMed Central

    Olmos, G.; Gabilondo, A. M.; Miralles, A.; Escriba, P. V.; García-Sevilla, J. A.

    1993-01-01

    1. The binding of [3H]-idazoxan in the presence of 10(-6) M (-)-adrenaline was used to quantitate non-adrenoceptor idazoxan binding sites (NAIBS) in the rat brain after treatment with various psychotropic drugs. 2. Chronic treatment (14 days) with the monoamine oxidase (MAO) inhibitors clorgyline (0.3-10 mg kg-1, i.p.) and pargyline (10 mg kg-1, i.p.), but not with Ro 41-1049 (1 mg kg-1, i.p.), markedly decreased (30-50%) the density of NAIBS in the cerebral cortex without any apparent change in the affinity of the radioligand. 3. Acute (1 day) and/or chronic treatments (14 days) with other psychotropic drugs such as desipramine (3 mg kg-1, i.p.), cocaine (10 mg kg-1, i.p.), reserpine (0.12 mg kg-1, s.c.), haloperidol (1 mg kg-1, i.p.) and diazepam (10 mg kg-1, i.p.) did not alter the density of NAIBS in the cerebral cortex. 4. In vitro, the propargylamines clorgyline, pargyline and deprenyl displaced the binding of [3H]-idazoxan to NAIBS from two distinct sites, but only clorgyline displayed an apparent very high affinity for a relevant population of NAIBS (KiH = 40 pM; KiL = 10.6 microM). The structurally diverse MAO inhibitors Ro 16-6491 (selective for MAO-B) and Ro 41-1049 (selective for MAO-A), as well as the other psychotropic drugs (desipramine, cocaine, reserpine and haloperidol) displaced the binding of [3H]-idazoxan to NAIBS monophasically and with very low potencies.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:8385528

  17. Anti-SSA/Ro antibodies and the heart: more than complete congenital heart block? A review of electrocardiographic and myocardial abnormalities and of treatment options

    PubMed Central

    Costedoat-Chalumeau, Nathalie; Amoura, Zahir; Villain, Elisabeth; Cohen, Laurence; Piette, Jean-Charles

    2005-01-01

    Apart from complete and incomplete congenital heart block (CHB), new cardiac manifestations related to anti-SSA/Ro antibodies have been reported in children born to mothers bearing these antibodies. These manifestations include transient fetal first-degree heart block, prolongation of corrected QT (QTc) interval, sinus bradycardia, late-onset cardiomyopathy, endocardial fibroelastosis and cardiac malformations. Anti-SSA/Ro antibodies are not considered pathogenic to the adult heart, but a prolongation of the QTc interval has recently been reported in adult patients and is still a matter of debate. Treatment of CHB is not well established and needs to be assessed carefully. The risks and benefits of prenatal fluorinated steroids are discussed. PMID:15743492

  18. Proposal for all-optical generation of multiple-frequency millimeter-wave signals for RoF system with multiple base stations using FWM in SOA.

    PubMed

    Zhang, Chongfu; Wang, Leyang; Qiu, Kun

    2011-07-18

    An approach for the multiple-frequency millimeter-wave (mm-wave) signals generation is proposed and demonstrated, specifically, which can be applied to a radio-over-fiber (RoF) system with multiple base stations (BSs). In this scheme, optical double sideband (ODSB) modulation is achieved using a Mach-Zehnder modulator (MZM) to generate the two-sideband signals. New frequencies of the optical signals are obtained by using four-wave mixing (FWM) in a semiconductor optical amplifier (SOA). At the BSs, two different frequencies are achieved using a comb optical filter (COF), and which then input a photodiode (PD) to generate the mm-wave signals with the frequencies of 20, 40 or 60 GHz for different BSs, by mixing of these frequencies components. Experimental results verify that the proposed multiple-frequency mm-wave signals generation scheme for a RoF system with multiple base stations can work properly.

  19. In vitro and in vivo evaluation of iodine-123-Ro 16-0154: A new imaging agent for SPECT investigations of benzodiazepine receptors

    SciTech Connect

    Beer, H.F.; Blaeuenstein, P.A.H.; Hasler, P.H.; Delaloye, B.; Riccabona, G.; Bangerl, I.; Hunkeler, W.; Bonetti, E.P.; Pieri, L.; Richards, J.G. )

    1990-06-01

    The flumazenil analogue, Ro 16-0154, a benzodiazepine partial inverse agonist, has been labeled by halogen exchange to enable SPECT investigations of central benzodiazepine receptors in the human brain. The purified {sup 123}I-Ro 16-0154 was found to be stable in rat brain preparations and to be metabolized in rat liver preparations. Its pharmacologic properties were comparable to those of flumazenil. The biodistribution in rats (1 hr postinjection) resulted in a high brain-to-blood ratio of 16. Clinical studies revealed images of the benzodiazepine receptor density in the brain. Since the receptor labeling was markedly reduced by injection of flumazenil, it was considered to be specific. Storage defects due to pathologic cerebral blood flow and changed receptor density were detected; this shows the potential usefulness of the substance for diagnostic purposes, e.g., the differential diagnosis of various forms of epilepsy.

  20. Wired/wireless access integrated RoF-PON with scalable generation of multi-frequency MMWs enabled by tunable optical frequency comb.

    PubMed

    Xiang, Yu; Jiang, Ning; Chen, Chen; Zhang, Chongfu; Qiu, Kun

    2013-08-26

    In this paper, a novel wired/wireless access integrated radio-over-fiber passive optical network (RoF-PON) system that utilizes scalable multiple-frequency millimeter-wave (MF-MMW) generation based on tunable optical frequency comb (TOFC) is proposed. The TOFC is performed by cascading a phase modulator (PM) and two intensity modulators (IMs), and with proper selection of the peak-to-peak voltage of the PM, a flat and effective optical comb with tens of frequency lines is achieved. The MF-MMWs are generated by beating the optical comb line pairs with an interval about 60 GHz. The feasibility and scalability of the proposed wired/wireless access integrated RoF-PON scheme are confirmed by the simulations of simultaneous distribution of wired and wireless data with the proposed multiple frequency MMW generation technology.

  1. Coupled orbital and spin evolution of the CoRoT-7 two-planet system using a Maxwell viscoelastic rheology

    NASA Astrophysics Data System (ADS)

    Rodríguez, A.; Callegari, N.; Correia, A. C. M.

    2016-12-01

    We investigate the orbital and rotational evolution of the CoRoT-7 two-planet system, assuming that the innermost planet behaves like a Maxwell body. We numerically resolve the coupled differential equations governing the instantaneous deformation of the inner planet together with the orbital motion of the system. We show that, depending on the relaxation time for the deformation of the planet, the orbital evolution has two distinct behaviours: for relaxation times shorter than the orbital period, we reproduce the results from classic tidal theories, for which the eccentricity is always damped. However, for longer relaxation times, the eccentricity of the inner orbit is secularly excited and can grow to high values. This mechanism provides an explanation for the present high eccentricity observed for CoRoT-7 b, as well as for other close-in super-Earths in multiple planetary systems.

  2. Optically pure γ-butyrolactones and epoxy esters via two stereocentered HKR of 3-substituted epoxy esters: a formal synthesis of (-)-paroxetine, Ro 67-8867 and (+)-eldanolide.

    PubMed

    Devalankar, Dattatray A; Karabal, Pratibha U; Sudalai, Arumugam

    2013-02-28

    The HKR of racemic anti- or syn-3-substituted epoxy esters catalyzed by a Co(III)salen complex provides ready access to the corresponding enantioenriched 3,4-disubstituted γ-butyrolactones and 3-substituted epoxy esters. This strategy has been successfully employed in the formal synthesis of biologically active 3,4-disubstituted piperidine derivatives, (-)-paroxetine and Ro 67-8867 and a natural product, (+)-eldanolide.

  3. Global distribution of water vapor observed by COSMIC GPS RO: Comparison with GPS radiosonde, NCEP and JRA-25 reanalysis data sets (Invited)

    NASA Astrophysics Data System (ADS)

    Pangaluru, K.

    2010-12-01

    In this study, the reliability and limitations of water vapor retrieval from COSMIC GPS RO measurements is investigated for tropical conditions. Detailed comparisons have been made between COSMIC and high resolution GPS radiosonde measurements across 13 tropical stations and model outputs (ERA-Interim, NCEP and JRA-25 reanalysis data sets). In comparison with independent techniques like radiosonde (Väisälä), it is found that COSMIC GPS RO wet profiles are more accurate up to 7-8 km (assuming radiosonde as standard technique). Latitudinal distribution of zonal mean specific humidity is considered at 1.4 km, 2.8 km, 4.2 km, 5.6 km, and 7.0 km altitude levels for detailed study. In general, comparisons with corresponding NCEP and JRA-25 reanalysis seasonal means show good agreement, although there are some discrepancies especially over convective regions of south America, Africa, and Indonesian regions. In tropical latitudes, the COSMIC specific humidity values are little higher than the model values. Large specific humidity values in intertropical converging zone (ITCZ) is clearly noticed with peak values centered at 5N to 10N in summer and ~3S in winter seasons. The zonal-mean meridional transport of water vapor across the globe is also estimated using the COSMIC and compared with the NCEP and JRA-25 data sets. The shape of the meridional mean transport closely resembles that of previous mean climate descriptions, but values trend to be notably larger than the model values. Being verified with different data sets, it is concluded that RO missions like COSMIC will provide a significantly extended data base which will allow for investigating the global distribution within much shorter time scales and offers a good data base for climatological study in the future when the long-term RO data sets become available.

  4. Engineering trypsin for inhibitor resistance.

    PubMed

    Batt, Anna R; St Germain, Commodore P; Gokey, Trevor; Guliaev, Anton B; Baird, Teaster

    2015-09-01

    The development of effective protease therapeutics requires that the proteases be more resistant to naturally occurring inhibitors while maintaining catalytic activity. A key step in developing inhibitor resistance is the identification of key residues in protease-inhibitor interaction. Given that majority of the protease therapeutics currently in use are trypsin-fold, trypsin itself serves as an ideal model for studying protease-inhibitor interaction. To test the importance of several trypsin-inhibitor interactions on the prime-side binding interface, we created four trypsin single variants Y39A, Y39F, K60A, and K60V and report biochemical sensitivity against bovine pancreatic trypsin inhibitor (BPTI) and M84R ecotin. All variants retained catalytic activity against small, commercially available peptide substrates [kcat /KM  = (1.2 ± 0.3) × 10(7) M(-1 ) s(-1) . Compared with wild-type, the K60A and K60V variants showed increased sensitivity to BPTI but less sensitivity to ecotin. The Y39A variant was less sensitive to BPTI and ecotin while the Y39F variant was more sensitive to both. The relative binding free energies between BPTI complexes with WT, Y39F, and Y39A were calculated based on 3.5 µs combined explicit solvent molecular dynamics simulations. The BPTI:Y39F complex resulted in the lowest binding energy, while BPTI:Y39A resulted in the highest. Simulations of Y39F revealed increased conformational rearrangement of F39, which allowed formation of a new hydrogen bond between BPTI R17 and H40 of the variant. All together, these data suggest that positions 39 and 60 are key for inhibitor binding to trypsin, and likely more trypsin-fold proteases.

  5. Spectrally efficient localized carrier distribution scheme for multiple-user DFT-S OFDM RoF- PON wireless access systems.

    PubMed

    Tao, Li; Yu, Jianjun; Yang, Qi; Luo, Ming; He, Zhixue; Shao, Yufeng; Zhang, Junwen; Chi, Nan

    2012-12-31

    We propose a modified localized carrier distribution scheme based on multi-tone generation to generate 60 GHz mm-wave for different wireless users and it improves the carrier utilization efficiency by 33.3%. The principle of multiple-user discrete Fourier transform spread optical orthogonal frequency-division multiplexing (DFT-S OFDM) Radio-over-fiber (RoF) system is presented. This multiple-user system is applicable to passive optical network (PON). Then we demonstrate a 8 x 4.65 Gb/s multiple-user DFT-S OFDM RoF-PON wireless access system over 40 km fiber link and 60 GHz wireless link using two localized carrier distribution scheme with different spectral efficiency. Compared to conventional OFDM, 2.3 dB reduction of receiver power using DFT-S OFDM modulation scheme and the calculated BER performance for 8 wireless users clearly demonstrates the feasibility of this spectrally efficient multiple-user RoF-PON scheme.

  6. Benzodiazepine receptor inverse agonists FG 7142 and RO 15-4513 both reverse some of the behavioral effects of ethanol in a holeboard test

    SciTech Connect

    Lister, R.G.

    1987-09-21

    The intrinsic effects of the benzodiazepine receptor inverse agonists RO 15-4513 and FG 7142 on the behavior of mice in a holeboard were investigated. Both drugs caused dose-related decreases in exploratory head-dipping. The highest dose of FG 7142 (40 mg/kg) also reduced locomotor activity. RO 15-4513 (1.5 and 3.0 mg/kg) and FG 7142 (10 and 20 mg/kg) reversed the reductions in the number of head-dips caused by ethanol (2 g/kg). The higher doses of these two drugs also partially reversed the locomotor stimulant action of ethanol. Animals that received ethanol in combination with either inverse agonist spent less time head-dipping than vehicle-treated controls. These data indicate that FG 7142 and RO 15-4513 can reverse, at least in part, some of the behavioral effects of ethanol. Neither drug significantly altered blood alcohol concentrations suggesting that the antagonism does not result from pharmacokinetic changes. 26 references, 5 figures, 2 tables.

  7. The location of a disease-associated polymorphism and genomic structure of the human 52-kDa Ro/SSA locus (SSA1)

    SciTech Connect

    Tsugu, H.; Horowitz, R.; Gibson, N.

    1994-12-01

    Sera from approximately 30% of patients with systemic lupus erythematosus (SLE) contain high titers of autoantibodies that bind to the 52-kDa Ro/SSA protein. We previously detected polymorphisms in the 52-kDa Ro/SSA gene (SSA1) with restriction enzymes, one of which is strongly associated with the presence of SLE (P < 0.0005) in African Americans. A higher disease frequency and more severe forms of the disease are commonly noted among these female patients. To determine the location and nature of this polymorphism, we obtained two clones that span 8.5 kb of the 52-kDa Ro/SSA locus including its upstream regulatory region. Six exons were identified, and their nucleotide sequences plus adjacent noncoding regions were determined. No differences were found between these exons and the coding region of one of the reported cDNAs. The disease-associated polymorphic site suggested by a restriction enzyme map and confirmed by DNA amplification and nucleotide sequencing was present upstream of exon 1. This polymorphism may be a genetic marker for a disease-related variation in the coding region for the protein or in the upstream regulatory region of this gene. Although this RFLP is present in Japanese, it is not associated with lupus in this race. 41 refs., 4 figs., 2 tabs.

  8. The tip of the iceberg: the frequency content of the δ Sct star HD 50844 from CoRoT space photometry

    NASA Astrophysics Data System (ADS)

    Poretti, E.; Mantegazza, L.; Rainer, M.; Uytterhoeven, K.; Michel, E.; Baglin, A.; Auvergne, M.; Catala, C.; Samadi, R.; Rodríguez, E.; Garrido, R.; Amado, P.; Martín-Ruiz, S.; Moya, A.; Suárez, J. C.; Baudin, F.; Zima, W.; Alvarez, M.; Mathias, P.; Paparó, M.; Pápics, P.; Plachy, E.

    2009-09-01

    It has been suggested that the detection of a wealth of very low amplitude modes in δ Sct stars was only a matter of signal-to-noise ratio. Access to this treasure, impossible from the ground, is one of the scientific aims of the space mission CoRoT, developed and operated by CNES. This work presents the results obtained on HD 50844: the 140,016 datapoints allowed us to reach the level of 10-5 mag in the amplitude spectra. The frequency analysis of the CoRoT timeseries revealed hundreds of terms in the frequency range 0-30 d-1. The initial guess that δ Sct stars have a very rich frequency content is confirmed. The spectroscopic mode identification gives theoretical support since very high-degree modes (up to = 14) are identified. We also prove that cancellation effects are not sufficient in removing the flux variations associated to these modes at the noise level of the CoRoT measurements. The ground-based observations indicate that HD 50844 is an evolved star that is slightly underabundant in heavy elements, located on the Terminal Age Main Sequence. The predominant term (f1 = 6.92 d-1) has been identified as the fundamental radial mode combining ground-based photometric and spectroscopic data.

  9. 19-nor vitamin-D analogs: a new class of potent inhibitors of proliferation and inducers of differentiation of human myeloid leukemia cell lines.

    PubMed

    Asou, H; Koike, M; Elstner, E; Cambell, M; Le, J; Uskokovic, M R; Kamada, N; Koeffler, H P

    1998-10-01

    We have studied the in vitro biological activities and mechanisms of action of 1,25-dihydroxyvitamin D3 (1,25D3) and nine potent 1,25D3 analogs on proliferation and differentiation of myeloid leukemia cell lines (HL-60, retinoic acid-resistant HL-60 [RA-res HL-60], NB4 and Kasumi-1). The common novel structural motiff for almost all the analogs included removal of C-19 (19-nor); each also had unsaturation of the side chain. All the compounds were potent; for example, the concentration of analogs producing a 50% clonal inhibition (ED50) ranged between 1 x 10(-9) to 4 x 10(-11) mol/L when using the HL-60 cell line. The most active compound [1, 25(OH)2-16,23E-diene-26-trifluoro-19-nor-cholecalciferol (Ro 25-9716)] had an ED50 of 4 x 10(-11) mol/L; in contrast, the 1,25D3 produced an ED50 of 10(-9) mol/L with the HL-60 target cells. Ro 25-9716 (10(-9) mol/L, 3 days) was a strong inducer of myeloid differentiation because it caused 92% of the HL-60 cells to express CD11b and 75% of these cells to reduce nitroblue tetrazolium (NBT). This compound (10(-8) mol/L, 4 days) also caused HL-60 cells to arrest in the G1 phase of the cell cycle (88% cells in G1 v 48% of the untreated control cells). The p27(kip-1), a cyclin-dependent kinase inhibitor which is important in blocking the cell cycle, was induced more quickly and potently by Ro 25-9716 (10(-7) mol/L, 0 to 5 days) than by 1,25D3, suggesting a possible mechanism by which these analogs inhibit proliferation of leukemic growth. The NB4 promyelocytic leukemia cells cultured with the Ro 25-9716 were also inhibited in their clonal proliferation (ED50, 5 x 10(-11) mol/L) and their expression of CD11b was enhanced (80% positive [10(-9) mol/L, 4 days] v 27% untreated NB4 cells). Moreover, the combination of Ro 25-9716 (10(-9) mol/L) and all-trans retinoic acid (ATRA, 10(-7) mol/L) induced 92% of the NB4 cells to reduce NBT, whereas only 26% of the cells became NBT positive after a similar exposure to the combination of 1,25D3

  10. Age-Associated Differences in MiRNA Signatures Are Restricted to CD45RO Negative T Cells and Are Associated with Changes in the Cellular Composition, Activation and Cellular Ageing.

    PubMed

    Teteloshvili, Nato; Kluiver, Joost; van der Geest, Kornelis S M; van der Lei, Roelof Jan; Jellema, Pytrick; Pawelec, Graham; Brouwer, Elisabeth; Kroesen, Bart-Jan; Boots, Annemieke M H; van den Berg, Anke

    2015-01-01

    MicroRNAs (miRNAs) have emerged as important players in the regulation of T-cell functionality. However, comprehensive insight into the extent of age-related miRNA changes in T cells is lacking. We established miRNA expression patterns of CD45RO- naïve and CD45RO+ memory T-cell subsets isolated from peripheral blood cells from young and elderly individuals. Unsupervised clustering of the miRNA expression data revealed an age-related clustering in the CD45RO- T cells, while CD45RO+ T cells clustered based on expression of CD4 and CD8. Seventeen miRNAs showed an at least 2-fold up- or downregulation in CD45RO- T cells obtained from young as compared to old donors. Validation on the same and independent samples revealed a statistically significant age-related upregulation of miR-21, miR-223 and miR-15a. In a T-cell subset analysis focusing on known age-related phenotypic changes, we showed significantly higher miR-21 and miR-223 levels in CD8+CD45RO-CCR7- TEMRA compared to CD45RO-CCR7+ TNAIVE-cells. Moreover, miR-21 but not miR-223 levels were significantly increased in CD45RO-CD31- post-thymic TNAIVE cells as compared to thymic CD45RO-CD31+ TNAIVE cells. Upon activation of CD45RO- TNAIVE cells we observed a significant induction of miR-21 especially in CD4+ T cells, while miR-223 levels significantly decreased only in CD4+ T cells. Besides composition and activation-induced changes, we showed a borderline significant increase in miR-21 levels upon an increasing number of population doublings in CD4+ T-cell clones. Together, our results show that ageing related changes in miRNA expression are dominant in the CD45RO- T-cell compartment. The differential expression patterns can be explained by age related changes in T-cell composition, i.e. accumulation of CD8+ TEMRA and CD4+ post-thymic expanded CD31- T cells and by cellular ageing, as demonstrated in a longitudinal clonal culture model.

  11. [New anticoagulants - direct thrombin inhibitors].

    PubMed

    Brand, B; Graf, L

    2012-11-01

    Direct thrombin-inhibitors inactivate not only free but also fibrin-bound thrombin. The group of parenteral direct thrombin-inhibitors includes the recombinant hirudins lepirudin and desirudin, the synthetic hirudin bivalirudin, and the small molecule argatroban. All these compounds do not interact with PF4/heparin-antibodies. Therefore, argatroban as well as bivalirudin are currently used to treat heparin-induced thrombocytopenia (HIT). The oral direct thrombin-inhibitor dabigatran etexilate is already licensed in many countries for the treatment of non-valvular atrial fibrillation. Dabigatran etexilate reveals a stable and predictable effect that allows a medication without dose adjustment or monitoring. The substance shows only few interactions with other drugs but strong inhibitors of p-glycoprotein can increase plasma levels of dabigatran substantially. After oral intake, the prodrug dabigatran etexilate is cleaved by esterase-mediated hydrolyses to the active compound dabigatran. Elimination of dabigatran is predominantly renal. Safety and efficacy of dabigatran etexilate were tested in an extensive clinical study program. Non-inferiority compared to current standard treatments was shown for prophylaxis of venous thromboembolic events after total knee and hip replacement, for stroke prevention in atrial fibrillation, and for treatment of acute venous thromboembolism. In daily practice, Dabigatran etexilate competes against the new direct factor Xa-