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Sample records for primary circulating metabolite

  1. Circulating prostacyclin metabolites in the dog

    International Nuclear Information System (INIS)

    Taylor, B.M.; Shebuski, R.J.; Sun, F.F.

    1983-01-01

    The present study was designed to determine the concentration of prostacyclin (PGI2) metabolites in the blood of the dog. After a bolus i.v. dose of [11 beta- 3 H]PGI2 (5 micrograms/kg) into each of five dogs, blood samples were withdrawn at 0.33, 0.67, 1, 3, 5, 20, 30, 60 and 120 min postdrug administration. Plasma samples were extracted and the radioactive components were analyzed by two-dimensional thin-layer chromatography with autoradiofluorography and radio-high-performance liquid chromatography. The compounds were identified by comparing their mobility with synthetic standards; only parallel responses observed in both tests constituted positive identification. Seven metabolites were identified by these two techniques: 6-keto-prostaglandin (PG)F1 alpha; 6-keto-PGE1; 2,3-dinor-6-keto-PGF 1 alpha; 2,3-dinor-13,14-dihydro-6,15-diketo-20-carboxyl PGF 1 alpha; and 2,3,18,19-tetranor-13,14-dihydro-6,15-diketo-20-carboxyl PGF 1 alpha. Several additional compounds, both polar and nonpolar in nature, which did not co-chromatograph with any of our standards were also detected. Early samples consisted predominantly of 6-keto-PGF 1 alpha and other 20-carbon metabolites. By 30 min, the predominant metabolites were the 16- and 18-carbon dicarboxylic acids. By 60 min, 85% of the radioactivity was associated with two unidentified polar compounds. The evidence suggests that 6-keto-PGF 1 alpha probably reflects only the transient levels of freshly entering PGI2 in the circulation, whereas levels of the most polar metabolites (e.g., dihydro-diketo-carboxyl tetranor-PGF 2 alpha) may be a better measure of the overall PGI2 presence due to its longer half-life in circulation

  2. Primary expectations of secondary metabolites

    Science.gov (United States)

    My program examines the plant secondary metabolites (i.e. phenolics) important for human health, and which impart the organoleptic properties that are quality indicators for fresh and processed foods. Consumer expectations such as appearance, taste, or texture influence their purchasing decisions; a...

  3. Metabolites associated with circulating interleukin-6 in older adults

    Science.gov (United States)

    Background: Circulating levels of the pro-inflammatory cytokine interleukin-6 (IL-6) levels are elevated in older adults, but mechanisms are unclear. In the current study, we used an untargeted metabolomic approach to develop an improved understanding about mechanisms related to circulating IL-6 in ...

  4. Circulating Metabolite Predictors of Glycemia in Middle-Aged Men and Women

    OpenAIRE

    W?rtz, Peter; Tiainen, Mika; M?kinen, Ville-Petteri; Kangas, Antti J.; Soininen, Pasi; Saltevo, Juha; Kein?nen-Kiukaanniemi, Sirkka; M?ntyselk?, Pekka; Lehtim?ki, Terho; Laakso, Markku; Jula, Antti; K?h?nen, Mika; Vanhala, Mauno; Ala-Korpela, Mika

    2012-01-01

    OBJECTIVE Metabolite predictors of deteriorating glucose tolerance may elucidate the pathogenesis of type 2 diabetes. We investigated associations of circulating metabolites from high-throughput profiling with fasting and postload glycemia cross-sectionally and prospectively on the population level. RESEARCH DESIGN AND METHODS Oral glucose tolerance was assessed in two Finnish, population-based studies consisting of 1,873 individuals (mean age 52 years, 58% women) and reexamined after 6.5 yea...

  5. Placental vitamin D metabolism and its associations with circulating vitamin D metabolites in pregnant women.

    Science.gov (United States)

    Park, Heyjun; Wood, Madeleine R; Malysheva, Olga V; Jones, Sara; Mehta, Saurabh; Brannon, Patsy M; Caudill, Marie A

    2017-12-01

    Background: Little is known about placental vitamin D metabolism and its impact on maternal circulating vitamin D concentrations in humans. Objective: This study sought to advance the current understanding of placental vitamin D metabolism and its role in modulating maternal circulating vitamin D metabolites during pregnancy. Design: Nested within a feeding study, 24 healthy pregnant women (26-29 wk of gestation) consumed a single amount of vitamin D (511 IU/d from diet and a cholecalciferol supplement) for 10 wk. Concentrations of placental and blood vitamin D metabolites and placental messenger RNA (mRNA) abundance of vitamin D metabolic pathway components were quantified. In addition, cultured human trophoblasts were incubated with 13 C-cholecalciferol to examine the intracellular generation and secretion of vitamin D metabolites along with the regulation of target genes. Results: In placental tissue, 25-hydroxyvitamin D 3 [25(OH)D 3 ] was strongly correlated ( r = 0.83, P D 3 Moreover, these placental metabolites were strongly correlated ( r ≤ 0.85, P ≤ 0.04) with their respective metabolites in maternal circulation. Positive associations ( P ≤ 0.045) were also observed between placental mRNA abundance of vitamin D metabolic components and circulating vitamin D metabolites [i.e., LDL-related protein 2 ( LRP2 , also known as megalin) with 25(OH)D 3 and the C3 epimer of 25(OH)D 3 [3-epi-25(OH)D 3 ]; cubilin ( CUBN ) with 25(OH)D 3 ; 25-hydroxylase ( CYP2R1 ) with 3-epi-25(OH)D 3 ; 24-hydroxylase ( CYP24A1 ) with 25(OH)D 3 , 3-epi-25(OH)D 3 , and 1,25-dihydroxyvitamin D 3 [1,25(OH) 2 D 3 ]; and 1α-hydroxylase [( CYP27B1 ) with 3-epi-25(OH)D 3 and 1,25(OH) 2 D 3 ]. Notably, in vitro experiments with trophoblasts showed increased production and secretion of 25(OH)D 3 and higher CYP24A1 gene transcript abundance in response to cholecalciferol treatment. Conclusions: The numerous associations of many of the placental biomarkers of vitamin D metabolism with

  6. Circulating metabolites and general cognitive ability and dementia: Evidence from 11 cohort studies.

    Science.gov (United States)

    van der Lee, Sven J; Teunissen, Charlotte E; Pool, René; Shipley, Martin J; Teumer, Alexander; Chouraki, Vincent; Melo van Lent, Debora; Tynkkynen, Juho; Fischer, Krista; Hernesniemi, Jussi; Haller, Toomas; Singh-Manoux, Archana; Verhoeven, Aswin; Willemsen, Gonneke; de Leeuw, Francisca A; Wagner, Holger; van Dongen, Jenny; Hertel, Johannes; Budde, Kathrin; Willems van Dijk, Ko; Weinhold, Leonie; Ikram, M Arfan; Pietzner, Maik; Perola, Markus; Wagner, Michael; Friedrich, Nele; Slagboom, P Eline; Scheltens, Philip; Yang, Qiong; Gertzen, Robert E; Egert, Sarah; Li, Shuo; Hankemeier, Thomas; van Beijsterveldt, Catharina E M; Vasan, Ramachandran S; Maier, Wolfgang; Peeters, Carel F W; Jörgen Grabe, Hans; Ramirez, Alfredo; Seshadri, Sudha; Metspalu, Andres; Kivimäki, Mika; Salomaa, Veikko; Demirkan, Ayşe; Boomsma, Dorret I; van der Flier, Wiesje M; Amin, Najaf; van Duijn, Cornelia M

    2018-01-06

    Identifying circulating metabolites that are associated with cognition and dementia may improve our understanding of the pathogenesis of dementia and provide crucial readouts for preventive and therapeutic interventions. We studied 299 metabolites in relation to cognition (general cognitive ability) in two discovery cohorts (N total = 5658). Metabolites significantly associated with cognition after adjusting for multiple testing were replicated in four independent cohorts (N total = 6652), and the associations with dementia and Alzheimer's disease (N = 25,872) and lifestyle factors (N = 5168) were examined. We discovered and replicated 15 metabolites associated with cognition including subfractions of high-density lipoprotein, docosahexaenoic acid, ornithine, glutamine, and glycoprotein acetyls. These associations were independent of classical risk factors including high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides, glucose, and apolipoprotein E (APOE) genotypes. Six of the cognition-associated metabolites were related to the risk of dementia and lifestyle factors. Circulating metabolites were consistently associated with cognition, dementia, and lifestyle factors, opening new avenues for prevention of cognitive decline and dementia. Copyright © 2018 the Alzheimer's Association. All rights reserved.

  7. Metabolome analysis - mass spectrometry and microbial primary metabolites

    DEFF Research Database (Denmark)

    Højer-Pedersen, Jesper Juul

    2008-01-01

    , and therefore sample preparation is critical for metabolome analysis. The three major steps in sample preparation for metabolite analysis are sampling, extraction and concentration. These three steps were evaluated for the yeast Saccharomyces cerevisiae with primary focus on analysis of a large number...... of metabolites by one method. The results highlighted that there were discrepancies between different methods. To increase the throughput of cultivation, S. cerevisiae was grown in microtitier plates (MTPs), and the growth was found to be comparable with cultivations in shake flasks. The carbon source was either...... a theoretical metabolome. This showed that in combination with the specificity of MS up to 84% of the metabolites can be identified in a high-accuracy ESI-spectrum. A total of 66 metabolites were systematically analyzed by positive and negative ESI-MS/MS with the aim of initiating a spectral library for ESI...

  8. Circulating Metabolites Associated with Alcohol Intake in the European Prospective Investigation into Cancer and Nutrition Cohort

    Directory of Open Access Journals (Sweden)

    Eline H. van Roekel

    2018-05-01

    Full Text Available Identifying the metabolites associated with alcohol consumption may provide insights into the metabolic pathways through which alcohol may affect human health. We studied associations of alcohol consumption with circulating concentrations of 123 metabolites among 2974 healthy participants from the European Prospective Investigation into Cancer and Nutrition (EPIC study. Alcohol consumption at recruitment was self-reported through dietary questionnaires. Metabolite concentrations were measured by tandem mass spectrometry (BIOCRATES AbsoluteIDQTM p180 kit. Data were randomly divided into discovery (2/3 and replication (1/3 sets. Multivariable linear regression models were used to evaluate confounder-adjusted associations of alcohol consumption with metabolite concentrations. Metabolites significantly related to alcohol intake in the discovery set (FDR q-value < 0.05 were further tested in the replication set (Bonferroni-corrected p-value < 0.05. Of the 72 metabolites significantly related to alcohol intake in the discovery set, 34 were also significant in the replication analysis, including three acylcarnitines, the amino acid citrulline, four lysophosphatidylcholines, 13 diacylphosphatidylcholines, seven acyl-alkylphosphatidylcholines, and six sphingomyelins. Our results confirmed earlier findings that alcohol consumption was associated with several lipid metabolites, and possibly also with specific acylcarnitines and amino acids. This provides further leads for future research studies aiming at elucidating the mechanisms underlying the effects of alcohol in relation to morbid conditions.

  9. Characterization of primary and secondary metabolites of leaf and ...

    African Journals Online (AJOL)

    This study evaluates the primary and secondary metabolite profiles of Eurycoma longifolia Jack (EL) stems and leaves to determine whether it can be utilized for therapeutic purposes as the roots. A total of six types of extracts were tested. The extracts showed high content of glycosaponins, polysaccharides, proteins and ...

  10. Steroid receptor profiling of vinclozolin and its primary metabolites

    International Nuclear Information System (INIS)

    Molina-Molina, Jose-Manuel; Hillenweck, Anne; Jouanin, Isabelle; Zalko, Daniel; Cravedi, Jean-Pierre; Fernandez, Mariana-Fatima; Pillon, Arnaud; Nicolas, Jean-Claude; Olea, Nicolas; Balaguer, Patrick

    2006-01-01

    Several pesticides and fungicides commonly used to control agricultural and indoor pests are highly suspected to display endocrine-disrupting effects in animals and humans. Endocrine disruption is mainly caused by the interference of chemicals at the level of steroid receptors: it is now well known that many of these chemicals can display estrogenic effects and/or anti-androgenic effects, but much less is known about the interaction of these compounds with other steroid receptors. Vinclozolin, a dicarboximide fungicide, like its primary metabolites 2-[[(3,5-dichlorophenyl)-carbamoyl]oxy]-2-methyl-3-butenoic acid (M1), and 3',5'-dichloro-2-hydroxy-2-methylbut-3-enanilide (M2), is known to bind androgen receptor (AR). Although vinclozolin and its metabolites were characterized as anti-androgens, relatively little is known about their effects on the function of the progesterone (PR), glucocorticoid (GR), mineralocorticoid (MR) or estrogen receptors (ERα and ERβ). Objectives of the study were to determine the ability of vinclozolin and its two primary metabolites to activate AR, PR, GR, MR and ER. For this purpose, we used reporter cell lines bearing luciferase gene under the control of wild type or chimeric Gal4 fusion AR, PR, GR, MR or ERs. We confirmed that all three were antagonists for AR, whereas only M2 was found a partial agonist. Interestingly, M2 was also a PR, GR and MR antagonist (MR >> PR > GR) while vinclozolin was an MR and PR antagonist. Vinclozolin, M1 and M2 were agonists for both ERs with a lower affinity for ERβ. Although the potencies of the fungicide and its metabolites are low when compared to natural ligands, their ability to act via more than one mechanism and the potential for additive or synergistic effect must be taken into consideration in the risk assessment process

  11. Steroid receptor profiling of vinclozolin and its primary metabolites.

    Science.gov (United States)

    Molina-Molina, José-Manuel; Hillenweck, Anne; Jouanin, Isabelle; Zalko, Daniel; Cravedi, Jean-Pierre; Fernández, Mariana-Fátima; Pillon, Arnaud; Nicolas, Jean-Claude; Olea, Nicolás; Balaguer, Patrick

    2006-10-01

    Several pesticides and fungicides commonly used to control agricultural and indoor pests are highly suspected to display endocrine-disrupting effects in animals and humans. Endocrine disruption is mainly caused by the interference of chemicals at the level of steroid receptors: it is now well known that many of these chemicals can display estrogenic effects and/or anti-androgenic effects, but much less is known about the interaction of these compounds with other steroid receptors. Vinclozolin, a dicarboximide fungicide, like its primary metabolites 2-[[(3,5-dichlorophenyl)-carbamoyl]oxy]-2-methyl-3-butenoic acid (M1), and 3',5'-dichloro-2-hydroxy-2-methylbut-3-enanilide (M2), is known to bind androgen receptor (AR). Although vinclozolin and its metabolites were characterized as anti-androgens, relatively little is known about their effects on the function of the progesterone (PR), glucocorticoid (GR), mineralocorticoid (MR) or estrogen receptors (ERalpha and ERbeta). Objectives of the study were to determine the ability of vinclozolin and its two primary metabolites to activate AR, PR, GR, MR and ER. For this purpose, we used reporter cell lines bearing luciferase gene under the control of wild type or chimeric Gal4 fusion AR, PR, GR, MR or ERs. We confirmed that all three were antagonists for AR, whereas only M2 was found a partial agonist. Interestingly, M2 was also a PR, GR and MR antagonist (MR>PR>GR) while vinclozolin was an MR and PR antagonist. Vinclozolin, M1 and M2 were agonists for both ERs with a lower affinity for ERbeta. Although the potencies of the fungicide and its metabolites are low when compared to natural ligands, their ability to act via more than one mechanism and the potential for additive or synergistic effect must be taken into consideration in the risk assessment process.

  12. An interaction map of circulating metabolites, immune gene networks, and their genetic regulation.

    Science.gov (United States)

    Nath, Artika P; Ritchie, Scott C; Byars, Sean G; Fearnley, Liam G; Havulinna, Aki S; Joensuu, Anni; Kangas, Antti J; Soininen, Pasi; Wennerström, Annika; Milani, Lili; Metspalu, Andres; Männistö, Satu; Würtz, Peter; Kettunen, Johannes; Raitoharju, Emma; Kähönen, Mika; Juonala, Markus; Palotie, Aarno; Ala-Korpela, Mika; Ripatti, Samuli; Lehtimäki, Terho; Abraham, Gad; Raitakari, Olli; Salomaa, Veikko; Perola, Markus; Inouye, Michael

    2017-08-01

    Immunometabolism plays a central role in many cardiometabolic diseases. However, a robust map of immune-related gene networks in circulating human cells, their interactions with metabolites, and their genetic control is still lacking. Here, we integrate blood transcriptomic, metabolomic, and genomic profiles from two population-based cohorts (total N = 2168), including a subset of individuals with matched multi-omic data at 7-year follow-up. We identify topologically replicable gene networks enriched for diverse immune functions including cytotoxicity, viral response, B cell, platelet, neutrophil, and mast cell/basophil activity. These immune gene modules show complex patterns of association with 158 circulating metabolites, including lipoprotein subclasses, lipids, fatty acids, amino acids, small molecules, and CRP. Genome-wide scans for module expression quantitative trait loci (mQTLs) reveal five modules with mQTLs that have both cis and trans effects. The strongest mQTL is in ARHGEF3 (rs1354034) and affects a module enriched for platelet function, independent of platelet counts. Modules of mast cell/basophil and neutrophil function show temporally stable metabolite associations over 7-year follow-up, providing evidence that these modules and their constituent gene products may play central roles in metabolic inflammation. Furthermore, the strongest mQTL in ARHGEF3 also displays clear temporal stability, supporting widespread trans effects at this locus. This study provides a detailed map of natural variation at the blood immunometabolic interface and its genetic basis, and may facilitate subsequent studies to explain inter-individual variation in cardiometabolic disease.

  13. Software sensor for primary metabolite production case of alcoholic fermentation

    Energy Technology Data Exchange (ETDEWEB)

    Roux, G.; Dahhou, B.; Queinnec, I. [Centre National de la Recherche Scientifique (CNRS), 31 - Toulouse (France)]|[Institut National des Sciences Appliquees (INSA), 31 - Toulouse (France); Goma, G. [Institut National des Sciences Appliquees (INSA), 31 - Toulouse (France)

    1995-12-31

    This paper investigate the application of an observer for state and parameter estimation to batch, continuous and fed batch fermentations for alcohol production taken as model for a primary metabolite production. This observer is provided to palliate the lack of suitable sensors for on-line biomass and ethanol concentrations measurements and to estimate the time varying specific growth rate. Estimates are obtained from an interlaced structure filter based on a `modified extended Kalman filter` by using on-line measurements of carbon dioxide outflow rate and substrate concentration. The filter algorithm was tested during batch, continuous and fed batch fermentation processes. The filter behaviour observed in the experiments gives good results with an agreement theory/practice. (authors) 18 refs.

  14. Natural circulation under variable primary mass inventories at BETHSY facility

    International Nuclear Information System (INIS)

    Bazin, P.; Clement, P.; Deruaz, R.

    1989-01-01

    BETHSY is a high pressure integral test facility which models a 3 loop Framatome PWR with the intent of studying PWR accidents. The BETHSY programme includes both accident transients and tests under successive steady state conditions. So far, tests of the latter type have been especially devoted to situations where natural circulation takes place in the primary coolant system (PCS). Tests 4.1a and 4.1a TC, the results of which are introduced, deal with PCS natural circulation patterns and related heat transport mechanisms under two different core power levels (2 and 5% of nominal power), variable primary mass inventory (100% to 30-40% according to core power) and at two different steam generator liquid levels (standard value and 1 meter). (orig.)

  15. The susceptibility of circulating human influenza viruses to tizoxanide, the active metabolite of nitazoxanide.

    Science.gov (United States)

    Tilmanis, Danielle; van Baalen, Carel; Oh, Ding Yuan; Rossignol, Jean-Francois; Hurt, Aeron C

    2017-11-01

    Nitazoxanide is a thiazolide compound that was originally developed as an anti-parasitic agent, but has recently been repurposed for the treatment of influenza virus infections. Thought to exert its anti-influenza activity via the inhibition of hemagglutinin maturation and intracellular trafficking in infected cells, the effectiveness of nitazoxanide in treating patients with non-complicated influenza is currently being assessed in phase III clinical trials. Here, we describe the susceptibility of 210 seasonal influenza viruses to tizoxanide, the active circulating metabolite of nitazoxanide. An optimised cell culture-based focus reduction assay was used to determine the susceptibility of A(H1N1)pdm09, A(H3N2), and influenza B viruses circulating in the southern hemisphere from the period March 2014 to August 2016. Tizoxanide showed potent in vitro antiviral activity against all influenza viruses tested, including neuraminidase inhibitor-resistant viruses, allowing the establishment of a baseline level of susceptibility for each subtype. Median EC 50 values (±IQR) of 0.48 μM (0.33-0.71), 0.62 μM (0.56-0.75), 0.66 μM (0.62-0.69), and 0.60 μM (0.51-0.67) were obtained for A(H1N1)pdm09, A(H3N2), B(Victoria lineage), and B(Yamagata lineage) influenza viruses respectively. There was no significant difference in the median baseline tizoxanide susceptibility for each influenza subtype tested. This is the first report on the susceptibility of circulating viruses to tizoxanide. The focus reduction assay format described is sensitive, robust, and less laborious than traditional cell based antiviral assays, making it highly suitable for the surveillance of tizoxanide susceptibility in circulating seasonal influenza viruses. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  16. Circulating zearalenone and its metabolites differ in women due to body mass index and food intake.

    Science.gov (United States)

    Mauro, T; Hao, L; Pop, L C; Buckley, B; Schneider, S H; Bandera, E V; Shapses, S A

    2018-04-17

    The environmental estrogen, zearalenone (ZEA), is found in the food supply from Fusarium fungal contamination in grains and sometimes used as a growth promoter for beef cattle. Long-term exposure to ZEA and its metabolites may present health risk due to higher estrogenic activity. Serum ZEA metabolites were measured to determine the exposure and the association with food intake in 48 overweight/obese women (52 ± 9 years). The free and conjugated ZEA indicated the highest detection rate of all the metabolites. Conjugated ZEA and total ZEA metabolites were lower (p = 0.02) in overweight/obese than normal weight women, and free metabolites were either the same or showed a trend to be higher. In addition, those with highest (280-480 g/d) compared those with lowest (metabolite concentrations (p metabolites. These findings indicate that ZEA and its metabolites are detectable in nearly all women and concentrations are associated with greater meat intake, and influenced by body mass index. Determining how the food supply influences human concentrations of ZEA metabolites is warranted, as well as determining vulnerable populations. Copyright © 2018. Published by Elsevier Ltd.

  17. Polymorphic Human Sulfotransferase 2A1 Mediates the Formation of 25-Hydroxyvitamin D3-3-O-Sulfate, a Major Circulating Vitamin D Metabolite in Humans.

    Science.gov (United States)

    Wong, Timothy; Wang, Zhican; Chapron, Brian D; Suzuki, Mizuki; Claw, Katrina G; Gao, Chunying; Foti, Robert S; Prasad, Bhagwat; Chapron, Alenka; Calamia, Justina; Chaudhry, Amarjit; Schuetz, Erin G; Horst, Ronald L; Mao, Qingcheng; de Boer, Ian H; Thornton, Timothy A; Thummel, Kenneth E

    2018-04-01

    Metabolism of 25-hydroxyvitamin D 3 (25OHD 3 ) plays a central role in regulating the biologic effects of vitamin D in the body. Although cytochrome P450-dependent hydroxylation of 25OHD 3 has been extensively investigated, limited information is available on the conjugation of 25OHD 3 In this study, we report that 25OHD 3 is selectively conjugated to 25OHD 3 -3- O -sulfate by human sulfotransferase 2A1 (SULT2A1) and that the liver is a primary site of metabolite formation. At a low (50 nM) concentration of 25OHD 3 , 25OHD 3 -3- O -sulfate was the most abundant metabolite, with an intrinsic clearance approximately 8-fold higher than the next most efficient metabolic route. In addition, 25OHD 3 sulfonation was not inducible by the potent human pregnane X receptor agonist, rifampicin. The 25OHD 3 sulfonation rates in a bank of 258 different human liver cytosols were highly variable but correlated with the rates of dehydroepiandrosterone sulfonation. Further analysis revealed a significant association between a common single nucleotide variant within intron 1 of SULT2A1 (rs296361; minor allele frequency = 15% in whites) and liver cytosolic SULT2A1 content as well as 25OHD 3 -3- O -sulfate formation rate, suggesting that variation in the SULT2A1 gene contributes importantly to interindividual differences in vitamin D homeostasis. Finally, 25OHD 3 -3- O -sulfate exhibited high affinity for the vitamin D binding protein and was detectable in human plasma and bile but not in urine samples. Thus, circulating concentrations of 25OHD 3 -3- O -sulfate appear to be protected from rapid renal elimination, raising the possibility that the sulfate metabolite may serve as a reservoir of 25OHD 3 in vivo, and contribute indirectly to the biologic effects of vitamin D. Copyright © 2018 by The American Society for Pharmacology and Experimental Therapeutics.

  18. Interactions Between a Belowground Herbivore and Primary and Secondary Root Metabolites in Wild Cabbage

    NARCIS (Netherlands)

    Van Geem, Moniek; Harvey, J.A.; Cortesero, A.M.; Raaijmakers, C.E.; Gols, R.

    2015-01-01

    Plants are attacked by both above- and belowground herbivores. Toxic secondary compounds are part of the chemical defense arsenal of plants against a range of antagonists, and are subject to genetic variation. Plants also produce primary metabolites (amino acids, nutrients, sugars) that function as

  19. Metabolism of all-trans-retinoic acid and all-trans-retinyl acetate. Demonstration of common physiological metabolites in rat small intestinal mucosa and circulation

    International Nuclear Information System (INIS)

    Cullum, M.E.; Zile, M.H.

    1985-01-01

    The kinetics and metabolism of physiological doses of all-trans-retinoic acid were examined in blood and small intestinal mucosa of vitamin A-depleted rats. A major portion of intrajugularly injected retinoic acid is rapidly (within 2 min) sequestered by tissues; subsequently 13-cis-retinoic acid and polar metabolites are released into circulation. All-trans-retinoic acid appears in small intestinal epithelium within 2 min after dosing and is the major radioactive compound there for at least 2 h. Retinoyl glucuronide and 13-cis-retinoic acid are early metabolites of all-trans-retinoic acid in the small intestine of bile duct-cannulated rats. Retinoyl glucuronide, the major metabolite of retinoic acid intestinal epithelium, in contrast to other polar metabolites, was not detected in circulation. An examination of [ 3 H]retinyl acetate metabolites under steady state conditions in vitamin A-repleted rats demonstrates the occurrence of all-trans-retinoic acid and 13-cis-retinoic acid in circulation and in intestinal epithelium, in a pattern similar to that found after injection of retinoic acid into vitamin A-depleted rats. These data establish that all-trans-retinoic acid, 13-cis-retinoic acid, and retinoyl glucuronide are physiological metabolites of vitamin A in target tissues, and therefore are important candidates as mediators of the biological effect of the vitamin

  20. FFTF primary system transition to natural circulation from low reactor power

    International Nuclear Information System (INIS)

    Bouchey, G.D.; Additon, S.L.; Nutt, W.T.

    1980-01-01

    Plans for reactor and primary loop natural circulation testing in the Fast Flux Test Facility (FFTF) are summarized. Detailed pretest planning with an emphasis on understanding the implications of process noise and model uncertainties for model verification and test acceptance are discussed for a transition to natural circulation in the reactor core and primary heat transport loops from initial conditions of 5% of rated reactor power and 75% of full flow

  1. Quantitative 1H-NMR Spectroscopy for Profiling Primary Metabolites in Mulberry Leaves

    Directory of Open Access Journals (Sweden)

    Qianqian Liang

    2018-03-01

    Full Text Available The primary metabolites in aqueous extract of mulberry (Morus alba L. leaves were characterized by using proton nuclear magnetic resonance (1H-NMR spectroscopy. With the convenience of resonance assignment, GABA together with the other 10 primary metabolites was simultaneously identified and quantified in one 1H-NMR spectrum. In this study, external calibration curves for metabolites were employed to calculate the concentrations of interests. The proposed quantitative approach was demonstrated with good linearity (r2 ranged in the interval of 0.9965–0.9999, precision, repeatability, stability (RSD values in the ranges of 0.35–4.89%, 0.77–7.13% and 0.28–2.33%, respectively and accuracy (recovery rates from 89.2% to 118.5%. The established 1H-NMR method was then successfully applied to quantify 11 primary metabolites in mulberry leaves from different geographical regions within a rapid analysis time and a simple sample preparation procedure.

  2. Primary and secondary metabolites production in signal grass around the year under nitrogen fertilizer

    OpenAIRE

    Syeda Maryam Hussain

    2016-01-01

    Plants produce a number of substances and products and primary and secondary metabolites (SM) are amongst them with many benefits but limitation as well. Usually, the fodder are not considered toxic to animals or as a source having higher SM. The Brachiaria decumbens has a considerable nutritional value, but it is considered as a toxic grass for causing photosensitization in animals, if the grass is not harvested for more than 30 days or solely. The absence of detailed information in the lite...

  3. Reverse primary-side flow in steam generators during natural circulation cooling

    International Nuclear Information System (INIS)

    Stumpf, H.; Motley, F.; Schultz, R.; Chapman, J.; Kukita, Y.

    1987-01-01

    A TRAC model of the Large Scale Test Facility with a 3-tube steam-generator model was used to analyze natural-circulation test ST-NC-02. For the steady state at 100% primary mass inventory, TRAC was in excellent agreement with the natural-circulation flow rate, the temperature distribution in the steam-generator tubes, and the temperature drop from the hot leg to the steam-generator inlet plenum. TRAC also predicted reverse flow in the long tubes. At reduced primary mass inventories, TRAC predicted the three natural-circulation flow regimes: single phase, two phase, and reflux condensation. TRAC did not predict the cyclic fill-and-dump phenomenon seen briefly in the test. TRAC overpredicted the two-phase natural-circulation flow rate. Since the core is well cooled at this time, the result is conservative. An important result of the analysis is that TRAC was able to predict the core dryout and heatup at approximately the same primary mass inventory as in the test. 4 refs., 8 figs., 2 tabs

  4. Identification of metabolites in the normal ovary and their transformation in primary and metastatic ovarian cancer.

    Science.gov (United States)

    Fong, Miranda Y; McDunn, Jonathan; Kakar, Sham S

    2011-01-01

    In this study, we characterized the metabolome of the human ovary and identified metabolic alternations that coincide with primary epithelial ovarian cancer (EOC) and metastatic tumors resulting from primary ovarian cancer (MOC) using three analytical platforms: gas chromatography mass spectrometry (GC/MS) and liquid chromatography tandem mass spectrometry (LC/MS/MS) using buffer systems and instrument settings to catalog positive or negative ions. The human ovarian metabolome was found to contain 364 biochemicals and upon transformation of the ovary caused changes in energy utilization, altering metabolites associated with glycolysis and β-oxidation of fatty acids--such as carnitine (1.79 fold in EOC, pcancer also displayed an enhanced oxidative stress response as indicated by increases in 2-aminobutyrate in EOC (1.46 fold, p = 0.0316) and in MOC (2.25 fold, povary, specifically N-acetylasparate and N-acetyl-aspartyl-glutamate, whose role in ovarian physiology has yet to be determined. These data enhance our understanding of the diverse biochemistry of the human ovary and demonstrate metabolic alterations upon transformation. Furthermore, metabolites with significant changes between groups provide insight into biochemical consequences of transformation and are candidate biomarkers of ovarian oncogenesis. Validation studies are warranted to determine whether these compounds have clinical utility in the diagnosis or clinical management of ovarian cancer patients.

  5. Inhibition of aromatase activity by methyl sulfonyl PCB metabolites in primary culture of human mammary fibroblasts

    Energy Technology Data Exchange (ETDEWEB)

    Berg, M. van den; Heneweer, M.; Geest, M. de; Sanderson, T. [Inst. for Risk Assessment Sciences and Utrecht Univ. (Netherlands); Jong, P. de [St. Antonius Hospital, Nieuwegein (Netherlands); Bergman, A. [Stockholm Univ., Stockholm (Sweden)

    2004-09-15

    Methyl sulfonyl PCB metabolites (MeSO2-PCBs) are persistent contaminants and are ubiquitously present in humans and the environment. Lipophilicity of MeSO2- PCB metabolites is similar to the parent compounds and they have been detected in human milk, adipose, liver and lung tissue. 4- MeSO2-PCB-149 is the most abundant PCB metabolite in human adipose tissue and milk at a level of 1.5 ng/g lipids. Human blood concentration of 4-MeSO2-PCB-149 is approximately 0.03 nM. 3- MeSO2-PCB-101 is the predominant PCB metabolite in muscle and blubber in wildlife, such as otter, mink and grey seal. In the environment, they have been linked to chronic and reproductive toxicity in exposed mink. Additionaly, some MeSO{sub 2}-PCBs have been shown to be glucocorticoid receptor (GR) antagonists. Since approximately 60% of all breast tumors are estrogen responsive, exposure to compounds that are able to alter estrogen synthesis through interference with the aromatase enzyme, can lead to changes in estrogen levels and possibly to accelerated or inhibit breast tumor growth. Therefore, it is important to identify exogenous compounds that can alter aromatase activity in addition to those compounds which have direct interaction with the estrogen receptor (ER). Aromatase (CYP19) comprises the ubiquitous flavoprotein, NADPH-cytochrome P450 reductase, and a unique cytochrome P450 that is exclusively expressed in estrogen producing cells. Previous studies have revealed that expression of the aromatase gene is regulated in a species- and tissue specific manner. In healthy breast tissue, the predominantly active aromatase promoter region I.4 is regulated by glucocorticoids and class I cytokines. Therefore, it is important to investigate possible aromatase inhibiting properties of MeSO{sub 2}-PCBs (as anti glucocorticoids?) in relevant human tissues. We used primary human mammary fibroblasts because of their role in breast cancer development. We compared the results in primary fibroblasts with

  6. Cultivar-Specific Changes in Primary and Secondary Metabolites in Pak Choi (Brassica Rapa, Chinensis Group by Methyl Jasmonate

    Directory of Open Access Journals (Sweden)

    Moo Jung Kim

    2017-05-01

    Full Text Available Glucosinolates, their hydrolysis products and primary metabolites were analyzed in five pak choi cultivars to determine the effect of methyl jasmonate (MeJA on metabolite flux from primary metabolites to glucosinolates and their hydrolysis products. Among detected glucosinolates (total 14 glucosinolates; 9 aliphatic, 4 indole and 1 aromatic glucosinolates, indole glucosinolate concentrations (153–229% and their hydrolysis products increased with MeJA treatment. Changes in the total isothiocyanates by MeJA were associated with epithiospecifier protein activity estimated as nitrile formation. Goitrin, a goitrogenic compound, significantly decreased by MeJA treatment in all cultivars. Changes in glucosinolates, especially aliphatic, significantly differed among cultivars. Primary metabolites including amino acids, organic acids and sugars also changed with MeJA treatment in a cultivar-specific manner. A decreased sugar level suggests that they might be a carbon source for secondary metabolite biosynthesis in MeJA-treated pak choi. The result of the present study suggests that MeJA can be an effective agent to elevate indole glucosinolates and their hydrolysis products and to reduce a goitrogenic compound in pak choi. The total glucosinolate concentration was the highest in “Chinese cabbage” in the control group (32.5 µmol/g DW, but indole glucosinolates increased the greatest in “Asian” when treated with MeJA.

  7. Cultivar and Year Rather than Agricultural Practices Affect Primary and Secondary Metabolites in Apple Fruit

    Science.gov (United States)

    Renard, Catherine M. G. C.; Plenet, Daniel; Gautier, Hélène; Touloumet, Line; Girard, Thierry; Simon, Sylvaine

    2015-01-01

    Many biotic and abiotic parameters affect the metabolites involved in the organoleptic and health value of fruits. It is therefore important to understand how the growers' decisions for cultivar and orchard management can affect the fruit composition. Practices, cultivars and/or year all might participate to determine fruit composition. To hierarchize these factors, fruit weight, dry matter, soluble solids contents, titratable acidity, individual sugars and organics acids, and phenolics were measured in three apple cultivars (‘Ariane’, ‘Melrose’ and ‘Smoothee’) managed under organic, low-input and conventional management. Apples were harvested at commercial maturity in the orchards of the cropping system experiment BioREco at INRA Gotheron (Drôme, 26) over the course of three years (2011, 2012 and 2013). The main factors affecting primary and secondary metabolites, in both apple skin and flesh, were by far the cultivar and the yearly conditions, while the management system had a very limited effect. When considering the three cultivars and the year 2011 to investigate the effect of the management system per se, only few compounds differed significantly between the three systems and in particular the total phenolic content did not differ significantly between systems. Finally, when considering orchards grown in the same pedoclimatic conditions and of the same age, instead of the usual organic vs. conventional comparison, the effect of the management system on the apple fruit quality (Fruit weight, dry matter, soluble solids content, titratable acidity, individual sugars, organic acids, and phenolics) was very limited to non-significant. The main factors of variation were the cultivar and the year of cropping rather than the cropping system. More generally, as each management system (e.g. conventional, organic…) encompasses a great variability of practices, this highlights the importance of accurately documenting orchard practices and design beside the

  8. Cultivar and Year Rather than Agricultural Practices Affect Primary and Secondary Metabolites in Apple Fruit.

    Directory of Open Access Journals (Sweden)

    Carine Le Bourvellec

    Full Text Available Many biotic and abiotic parameters affect the metabolites involved in the organoleptic and health value of fruits. It is therefore important to understand how the growers' decisions for cultivar and orchard management can affect the fruit composition. Practices, cultivars and/or year all might participate to determine fruit composition. To hierarchize these factors, fruit weight, dry matter, soluble solids contents, titratable acidity, individual sugars and organics acids, and phenolics were measured in three apple cultivars ('Ariane', 'Melrose' and 'Smoothee' managed under organic, low-input and conventional management. Apples were harvested at commercial maturity in the orchards of the cropping system experiment BioREco at INRA Gotheron (Drôme, 26 over the course of three years (2011, 2012 and 2013. The main factors affecting primary and secondary metabolites, in both apple skin and flesh, were by far the cultivar and the yearly conditions, while the management system had a very limited effect. When considering the three cultivars and the year 2011 to investigate the effect of the management system per se, only few compounds differed significantly between the three systems and in particular the total phenolic content did not differ significantly between systems. Finally, when considering orchards grown in the same pedoclimatic conditions and of the same age, instead of the usual organic vs. conventional comparison, the effect of the management system on the apple fruit quality (Fruit weight, dry matter, soluble solids content, titratable acidity, individual sugars, organic acids, and phenolics was very limited to non-significant. The main factors of variation were the cultivar and the year of cropping rather than the cropping system. More generally, as each management system (e.g. conventional, organic… encompasses a great variability of practices, this highlights the importance of accurately documenting orchard practices and design beside

  9. Experimental Study on the Natural Circulation Characteristics in the Primary Loop of the SMART Reactor by using the VISTA Facility

    International Nuclear Information System (INIS)

    Park, Hyun-Sik; Choi, Ki-Yong; Cho, Seok; Yi, Sung-Jae; Park, Choon-Kyung; Chung, Moon-Ki

    2007-01-01

    The SMART uses a two-phase natural circulation in the PRHRS loop to remove the heat from the steam generators to the PRHRS heat exchangers, while a single phase natural circulation occurs in the primary loop to transfer the decay heat from the core to the steam generator. Natural circulation operation with a power range of 20 ∼ 25% was considered for SMART and nowadays the possibility of increasing the power level during the natural circulation operation is being investigated. Previously Park et al. performed several experiments by using the VISTA facility on the thermal-hydraulic characteristics of the PRHRS for the SMART-P, which includes a single-phase natural circulation in the primary loop. From the analysis with the TASS-SMR code it was shown that the reference temperature for the primary steam generator inlet temperature should be increased in order to compensate for the decreased core flow. To investigate the possibility of an increase of the power and reference temperature, it is necessary to get experimental data to characterize the natural circulation phenomena in the primary loop of the SMART. In this paper, the characteristics of natural circulation in the primary loop are experimentally investigated during various operational conditions by using the VISTA facility

  10. Radionuclide analyses taken during primary coolant decontamination at Three Mile Island indicate general circulation

    International Nuclear Information System (INIS)

    Hofstetter, K.J.; Baston, V.F.; Hitz, C.G.; Malinauskas, A.P.

    1983-01-01

    Radionuclide concentration data taken during decontamination of the primary reactor coolant system at Three Mile Island by a feed-and-bleed process have provided information on future defueling operations. Analysis of the radiocesium concentrations in samples taken at the letdown point indicates general circulation within the primary system, including the reactor vessel and both steam generators. A standard dilution model with parameters consistent with engineering estimates (volume, flow rate, etc.) accurately predicts the radiocesium decontamination rates. Unlike cesium, the behavior of other principal soluble radionuclides ( 90 Sr and 3 H) cannot be readily described by dilution theory. A significant appearance rate is observed for 90 Sr suggesting a chemical solubility mechanism. The use of processed water containing high 3 H for makeup causes uncertainty in the interpretation of the 3 H analysis

  11. Impact of shelf life on content of primary and secondary metabolites in apple (Malus domestica Borkh.).

    Science.gov (United States)

    Veberic, Robert; Schmitzer, Valentina; Petkovsek, Maja M; Stampar, Franci

    2010-01-01

    In this study, we evaluated the changes in apple fruit quality during shelf life. After a month of cold storage, apples of cultivars "Jonagold" and "Golden Delicious" were exposed to ambient temperatures for 21 d, with subsequent sampling every 3 or 4 d. Fruit firmness, changes in amounts of sugars, malic acid, and phenolics were observed during shelf life. Chemical analyses were done with HPLC-PDA system. An interchange between various sugars was noticed, but in general, the sum of sugars remained at the same level. The content of malic acid remained stable or dropped, resulting in sweeter fruit. Levels of phenolics were more constant in the pulp of both cultivars analyzed, while in the peel, the changes were more pronounced. In the pulp, a peak in the content of hydroxycinnamic acids and flavanols was noticed on the 2nd or 3rd sampling and afterwards, the amounts remained constant. In the peel an initial decrease of all analyzed phenolic groups was observed in both cultivars, however it was more pronounced in "Jonagold." It can be concluded that changes in primary and secondary metabolites are not the main reason for the lower quality of fruit exposed to ambient temperatures. On the other hand, fruit firmness might be the limiting factor for shelf life duration. © 2010 Institute of Food Technologists®

  12. Profiling of primary metabolites and flavonols in leaves of two table grape varieties collected from semiarid and temperate regions.

    Science.gov (United States)

    Harb, Jamil; Alseekh, Saleh; Tohge, Takayuki; Fernie, Alisdair R

    2015-09-01

    Cultivation of grapes in West Bank - Palestine is very old and a large number of grape varieties exist as a result of continuous domestication over thousands of years. This rich biodiversity has highly influenced the consumer behavior of local people, who consume both grape berries and leaves. However, studies that address the contents of health-promoting metabolites in leaves are scarce. Accordingly the aim of this study is to assess metabolite levels in leaves of two grape varieties that were collected from semiarid and temperate regions. Metabolic profiling was conducted using GC-MS and LC-MS. The obtained results show that abiotic stresses in the semiarid region led to clear changes in primary metabolites, in particular in amino acids, which exist at very high levels. By contrast, qualitative and genotype-dependent differences in secondary metabolites were observed, whereas abiotic stresses appear to have negligible effect on the content of these metabolites. The qualitative difference in the flavonol profiles between the two genotypes is most probably related to differential expression of specific genes, in particular flavonol 3-O-rhamnosyltransferase, flavonol-3-O-glycoside pentosyltransferases and flavonol-3-O-d-glucosidel-rhamnosyltransferase by 'Beituni' grape leaves, which led to much higher levels of flavonols with rutinoside, pentoside, and rhamnoside moieties with this genotype. Copyright © 2015 Elsevier Ltd. All rights reserved.

  13. Feedback control of primary circulation pump of PIUS-Type reactor

    International Nuclear Information System (INIS)

    Fujii, Mikiya; Anoda, Yoshinari; Murata, Hideo; Yonomoto, Taisuke; Kukita, Yutaka; Tasaka, Kanji.

    1991-05-01

    In operating the PIUS-Type reactor, it is required to keep stationary density interfaces between the primary loop hot water and the poison tank cold, borated water by maintaining pressure balance between the primary-loop and the poison-tank. The authors have developed a primary circulation pump speed control system and tested it in small-scale experiments. This control system regulates the pump speed based on measurements of the density lock differential pressure which is proportional to the elevation of the interface in the density lock. This pump speed control facilitated the normal plant operation which included core power changes. However, the elevation of the density interface indicated oscillatory behavior when the pump speed was regulated as a linear function of the density lock differential pressure. The mechanism responsible for such oscillatory behavior was found to be manometric oscillations that could be eliminated by adding a damping term to compensate for the mechanical delay of the primary pump speed. The passive shutdown function of the reactor was retained by setting an upper limit to the pump speed. This was confirmed in a loss-of-feedwater abnormal transient test. (author)

  14. Evaluation of primary and secondary metabolites in selected varieties of potatoes.

    Directory of Open Access Journals (Sweden)

    Ján Mareček

    2016-01-01

    Full Text Available The aim of study was to determine primary and secondary metabolites in selected varieties of potatoes. Potatoes (Solanum tuberosum L. are good source of bioactive compounds, mainly phenols as one of the most important components. The chemical composition with reducing sugar, starch, ascorbic acid, total polyphenol and flavonoid content were analyzed in five potato varieties (Agria, Marabel, Red Anna, Picasso, Princess. Values of dry matter content ranged from 20.34 to 23.64%. In terms of tubers storage, its content above 20% is required. The highest level of starch was detected in variety Princess (16.82%. The lowest reducing sugar content was recorded by variety Marabel (0.08%. Similarly, low values reached varieties Princess (0.12%, Agria (0.14 and Red Anna (0.16%. These would be appropriate to use for food processing and for production of fried potato chips or fries. Variety Red Anna reached the highest amount of vitamin C (73.72 mg.kg-1. The lower levels of this vitamin showed tubers of varieties Picasso (35.02 mg.kg-1 and Princess (36.89 mg.kg-1. The antioxidant activity was measured with radical scavenging assays using 1,1-diphenyl-2-picrylhydrazyl (DPPH radical as well as phosphomolybdenic assay. Potato varieties contained high levels of total polyphenols (0.474 – 1.550 mg GAE per dry weight and flavonoids (1.407 – 15.933 μg QE per dry weight. The consumption of potatoes can provide nutritional value along with antioxidant potential that can be helpful for proper functioning of the body physiological systems. Statistical evaluation by the single factor analysis of variance detected high significant impact of variety on the content of all the analytical parameters in evaluated varieties of potato tubers. Normal 0 21 false false false SK X-NONE X-NONE

  15. Quantitative Rationalization of Gemfibrozil Drug Interactions: Consideration of Transporters-Enzyme Interplay and the Role of Circulating Metabolite Gemfibrozil 1-O-β-Glucuronide.

    Science.gov (United States)

    Varma, Manthena V S; Lin, Jian; Bi, Yi-an; Kimoto, Emi; Rodrigues, A David

    2015-07-01

    Gemfibrozil has been suggested as a sensitive cytochrome P450 2C8 (CYP2C8) inhibitor for clinical investigation by the U.S. Food and Drug Administration and the European Medicines Agency. However, gemfibrozil drug-drug interactions (DDIs) are complex; its major circulating metabolite, gemfibrozil 1-O-β-glucuronide (Gem-Glu), exhibits time-dependent inhibition of CYP2C8, and both parent and metabolite also behave as moderate inhibitors of organic anion transporting polypeptide 1B1 (OATP1B1) in vitro. Additionally, parent and metabolite also inhibit renal transport mediated by OAT3. Here, in vitro inhibition data for gemfibrozil and Gem-Glu were used to assess their impact on the pharmacokinetics of several victim drugs (including rosiglitazone, pioglitazone, cerivastatin, and repaglinide) by employing both static mechanistic and dynamic physiologically based pharmacokinetic (PBPK) models. Of the 48 cases evaluated using the static models, about 75% and 98% of the DDIs were predicted within 1.5- and 2-fold of the observed values, respectively, when incorporating the interaction potential of both gemfibrozil and its 1-O-β-glucuronide. Moreover, the PBPK model was able to recover the plasma profiles of rosiglitazone, pioglitazone, cerivastatin, and repaglinide under control and gemfibrozil treatment conditions. Analyses suggest that Gem-Glu is the major contributor to the DDIs, and its exposure needed to bring about complete inactivation of CYP2C8 is only a fraction of that achieved in the clinic after a therapeutic gemfibrozil dose. Overall, the complex interactions of gemfibrozil can be quantitatively rationalized, and the learnings from this analysis can be applied in support of future predictions of gemfibrozil DDIs. Copyright © 2015 by The American Society for Pharmacology and Experimental Therapeutics.

  16. Circulating nitric oxide metabolites and cardiovascular changes in the turtle Trachemys scripta during normoxia, anoxia and reoxygenation

    DEFF Research Database (Denmark)

    Jacobsen, Søren B; Hansen, Marie N; Jensen, Nini Skovgaard

    2012-01-01

    Turtles of the genus Trachemys show a remarkable ability to survive prolonged anoxia. This is achieved by a strong metabolic depression, redistribution of blood flow and high levels of antioxidant defence. To understand whether nitric oxide (NO), a major regulator of vasodilatation and oxygen...... consumption, may be involved in the adaptive response of Trachemys to anoxia, we measured NO metabolites (nitrite, S-nitroso, Fe-nitrosyl and N-nitroso compounds) in the plasma and red blood cells of venous and arterial blood of Trachemys scripta turtles during normoxia and after anoxia (3 h......-nitroso compounds were present at high micromolar levels under normoxia and increased further after anoxia and reoxygenation, suggesting NO generation from nitrite catalysed by deoxygenated haemoglobin, which in turtle had a higher nitrite reductase activity than in hypoxia-intolerant species. Taken together...

  17. The Faroe shelf circulation and its potential impact on the primary production

    Science.gov (United States)

    Rasmussen, Till A. S.; Olsen, Steffen M.; Hansen, Bogi; Hátún, Hjálmar; Larsen, Karin M. H.

    2014-10-01

    The ecosystem on the Faroe shelf has been shown to be tightly controlled by the primary production. It has been suggested that the primary production is governed by the physical processes controlling this water mass. The objective of this study is to identify the physical control mechanisms that control this water mass, link these to the interannual variability of the chlorophyll content on the Faroe shelf and through this discuss the influence on the primary production. In order to achieve this, a 10 year hindcast (2000-2009) with a regional ocean circulation model has been set up for the focus area. Results are compared with measurements on the Faroe shelf. The model reproduces the clockwise residual circulation around the Faroe Islands. The vertical velocity profile is validated using observations at a location west of the Islands. Observations show a logarithmic profile in the entire water column indicating a fully developed boundary layer. The modeled profile matches the observations in the bottom part of the water column, however the thickness of the bottom boundary layer is underestimated, which results in a constant profile in the upper part of the water column. As a consequence, the modeled velocity in the upper part of the water column is up to 20% lower than the observed velocity. The direction of the modeled velocity profile compares well with observations. The model realistically forms the partly isolated unique shelf water mass. Years with anomalously early and persistent modeled spring stratification correspond with years with a high on-shelf chlorophyll concentration. An integration of the exchange across the 120 m isobath shows intense water mass exchange across this depth contour. The major part of this includes tidal shifting of the front between on-shelf and off-shelf waters and is associated with little effective water mass exchange. The result is a shelf water mass that is relatively isolated. The modeled net exchange is constituted by an on

  18. Simultaneous quantification of caffeine and its three primary metabolites in rat plasma by liquid chromatography-tandem mass spectrometry.

    Science.gov (United States)

    Choi, Eu Jin; Bae, Soo Hyeon; Park, Jung Bae; Kwon, Min Jo; Jang, Su Min; Zheng, Yu Fen; Lee, Young Sun; Lee, Su-Jun; Bae, Soo Kyung

    2013-12-01

    A rapid, sensitive, simple and accurate LC-MS/MS method for the simultaneous quantitation of caffeine, and its three primary metabolites, theobromine, paraxanthine, and theophylline, in rat plasma was developed and validated. Chromatographic separation was performed on an Agilent Poroshell 120 EC-C18 column using 1 μg/mL acetaminophen as an internal standard. Each sample was run at 0.5 mL/min for a total run time of 7 min/sample. Detection and quantification were performed using a mass spectrometer in selected reaction-monitoring mode with positive electrospray ionization. The lower limit of quantification was 5 ng/mL for all analytes with linear ranges up to 5000 ng/mL for caffeine and 1000 ng/mL for its metabolites. The coefficient of variation for assay precision was less than 12.6%, with an accuracy of 93.5-114%. The assay was successfully applied to determine plasma concentrations of caffeine, theobromine, paraxanthine, and theophylline in rat administered various energy drinks containing the same caffeine content. Various energy drinks exhibited considerable variability in the pharmacokinetic profiles of caffeine and its three primary metabolites, even containing the same caffeine. Different additives of energy drinks might contribute to these results. Copyright © 2013 Elsevier Ltd. All rights reserved.

  19. Metabolite profiling approach reveals the interface of primary and secondary metabolism in colored cauliflowers (Brassica oleracea L. ssp. botrytis).

    Science.gov (United States)

    Park, Soo-Yun; Lim, Sun-Hyung; Ha, Sun-Hwa; Yeo, Yunsoo; Park, Woo Tae; Kwon, Do Yeon; Park, Sang Un; Kim, Jae Kwang

    2013-07-17

    In the present study, carotenoids, anthocyanins, and phenolic acids of cauliflowers ( Brassica oleracea L. ssp. botrytis) with various colored florets (white, yellow, green, and purple) were characterized to determine their phytochemical diversity. Additionally, 48 metabolites comprising amino acids, organic acids, sugars, and sugar alcohols were identified using gas chromatography-time-of-flight mass spectrometry (GC-TOFMS). Carotenoid content was considerably higher in green cauliflower; anthocyanins were detected only in purple cauliflower. Phenolic acids were higher in both green and purple cauliflower. Results of partial least-squares discriminant, Pearson correlation, and hierarchical clustering analyses showed that green cauliflower is distinct on the basis of the high levels of amino acids and clusters derived from common or closely related biochemical pathways. These results suggest that GC-TOFMS-based metabolite profiling, combined with chemometrics, is a useful tool for determining phenotypic variation and identifying metabolic networks connecting primary and secondary metabolism.

  20. Phenotypic and Functional Alterations in Circulating Memory CD8 T Cells with Time after Primary Infection.

    Directory of Open Access Journals (Sweden)

    Matthew D Martin

    2015-10-01

    Full Text Available Memory CD8 T cells confer increased protection to immune hosts upon secondary viral, bacterial, and parasitic infections. The level of protection provided depends on the numbers, quality (functional ability, and location of memory CD8 T cells present at the time of infection. While primary memory CD8 T cells can be maintained for the life of the host, the full extent of phenotypic and functional changes that occur over time after initial antigen encounter remains poorly characterized. Here we show that critical properties of circulating primary memory CD8 T cells, including location, phenotype, cytokine production, maintenance, secondary proliferation, secondary memory generation potential, and mitochondrial function change with time after infection. Interestingly, phenotypic and functional alterations in the memory population are not due solely to shifts in the ratio of effector (CD62Llo and central memory (CD62Lhi cells, but also occur within defined CD62Lhi memory CD8 T cell subsets. CD62Lhi memory cells retain the ability to efficiently produce cytokines with time after infection. However, while it is was not formally tested whether changes in CD62Lhi memory CD8 T cells over time occur in a cell intrinsic manner or are due to selective death and/or survival, the gene expression profiles of CD62Lhi memory CD8 T cells change, phenotypic heterogeneity decreases, and mitochondrial function and proliferative capacity in either a lymphopenic environment or in response to antigen re-encounter increase with time. Importantly, and in accordance with their enhanced proliferative and metabolic capabilities, protection provided against chronic LCMV clone-13 infection increases over time for both circulating memory CD8 T cell populations and for CD62Lhi memory cells. Taken together, the data in this study reveal that memory CD8 T cells continue to change with time after infection and suggest that the outcome of vaccination strategies designed to elicit

  1. Mutational analysis of circulating tumor cells from colorectal cancer patients and correlation with primary tumor tissue.

    Directory of Open Access Journals (Sweden)

    Anna Lyberopoulou

    Full Text Available Circulating tumor cells (CTCs provide a non-invasive accessible source of tumor material from patients with cancer. The cellular heterogeneity within CTC populations is of great clinical importance regarding the increasing number of adjuvant treatment options for patients with metastatic carcinomas, in order to eliminate residual disease. Moreover, the molecular profiling of these rare cells might lead to insight on disease progression and therapeutic strategies than simple CTCs counting. In the present study we investigated the feasibility to detect KRAS, BRAF, CD133 and Plastin3 (PLS3 mutations in an enriched CTCs cell suspension from patients with colorectal cancer, with the hypothesis that these genes` mutations are of great importance regarding the generation of CTCs subpopulations. Subsequently, we compared CTCs mutational status with that of the corresponding primary tumor, in order to access the possibility of tumor cells characterization without biopsy. CTCs were detected and isolated from blood drawn from 52 colorectal cancer (CRC patients using a quantum-dot-labelled magnetic immunoassay method. Mutations were detected by PCR-RFLP or allele-specific PCR and confirmed by direct sequencing. In 52 patients, discordance between primary tumor and CTCs was 5.77% for KRAS, 3.85% for BRAF, 11.54% for CD133 rs3130, 7.69% for CD133 rs2286455 and 11.54% for PLS3 rs6643869 mutations. Our results support that DNA mutational analysis of CTCs may enable non-invasive, specific biomarker diagnostics and expand the scope of personalized medicine for cancer patients.

  2. Design and Selection of Innovative Primary Circulation Pumps for GEN-IV Lead Fast Reactors

    Directory of Open Access Journals (Sweden)

    Walter Borreani

    2017-12-01

    Full Text Available Although Lead-cooled Fast Reactor (LFR is not a new concept, it continues to be an example of innovation in the nuclear field. Recently, there has been strong interest in liquid lead (Pb or liquid lead–bismuth eutectic (LBE both critical and subcritical systems in a relevant number of Countries, including studies performed in the frame of GENERATION-IV initiative. In this paper, the theoretical and computational findings for three different designs of Primary Circulation Pump (PCP evolving liquid lead (namely the jet pump, the Archimedean pump and the blade pump are presented with reference to the ALFRED (Advanced Lead Fast Reactor European Demonstrator design. The pumps are first analyzed from the theoretical point of view and then modeled with a 3D CFD code. Required design performance of the pumps are approximatively around an effective head of 2 bar with a mass flow rate of 5000 kg/s. Taking into account the geometrical constraints of the reactor and the fluid dynamics characteristics of the molten lead, the maximum design velocity for molten lead fluid flow of 2 m/s may be exceeded giving rise to unacceptable erosion phenomena of the blade or rotating component of the primary pumping system. For this reason a deep investigation of non-conventional axial pumps has been performed. The results presented shows that the design of the jet pump looks like beyond the current technological feasibility while, once the mechanical challenges of the Archimedean (screw pump and the fluid-dynamic issues of the blade pump will be addressed, both could represent viable solutions as PCP for ALFRED. Particularly, the blade pump shows the best performance in terms of pressure head generated in normal operation conditions as well as pressure drop in locked rotor conditions. Further optimizations (mainly for what the geometrical configuration is concerned are still necessary.

  3. Feasibility analysis of the Primary Loop of Pool-Type Natural Circulating Nuclear Reactor Dedicated to Seawater Desalination

    Energy Technology Data Exchange (ETDEWEB)

    Jeong, Woonho; Jeong, Yong Hoon [KAIST, Daejeon (Korea, Republic of)

    2016-05-15

    In this study, the feasibility of natural circulation was evaluated for the reference plant AHR400 (Advanced Heating Reactor 400MWth). AHR400 is a pool-type desalination-dedicated nuclear reactor. As a consequence, AHR400 has low operating pressure and temperature which provides large safety margin. Removal of the reactor coolant pump from the AHR400 will enforce integrity of the reactor vessel and passive safety feature. Therefore, the study also tried to find out optimized primary loop design to achieve total natural circulation of the coolant. Natural circulation capacity of the primary loop of the desalination dedicated nuclear reactor AHR400 was evaluated. It was concluded that to remove RCP from the AHR400 and operates the reactor only by natural circulation of the coolant is impossible. Decreased core power as half make removal of RCP possible with 15m central height difference between the core and IHXs. Furthermore, validation and modification of pressure loss coefficients by small-scaled natural circulation experiment at a pool-type reactor would provide more accurate results.

  4. Changes of primary and secondary metabolites in barley plants exposed to CdO nanoparticles

    Czech Academy of Sciences Publication Activity Database

    Večeřová, Kristýna; Večeřa, Zbyněk; Dočekal, Bohumil; Oravec, Michal; Pompeiano, Antonio; Tříska, Jan; Urban, Otmar

    2016-01-01

    Roč. 218, NOV (2016), s. 207-218 ISSN 0269-7491 R&D Projects: GA MŠk(CZ) LO1415; GA ČR(CZ) GAP503/11/2315; GA ČR(CZ) GBP503/12/G147; GA MŠk(CZ) LD15039 Institutional support: RVO:67179843 ; RVO:68081715 Keywords : Barley * CdO nanoparticles * Gas chromatography * High performance liquid chromatography * Mass spectrometry * Plant metabolites Subject RIV: EH - Ecology, Behaviour; CB - Analytical Chemistry, Separation (UIACH-O) Impact factor: 5.099, year: 2016

  5. Interactions between atmospheric circulation, nutrient deposition, and tropical forest primary production (Invited)

    Science.gov (United States)

    Randerson, J. T.; Chen, Y.; Rogers, B. M.; Morton, D. C.; van der Werf, G.; Mahowald, N. M.

    2010-12-01

    Tropical forests influence regional and global climate by means of several pathways, including by modifying surface energy exchange and by forming clouds. High levels of precipitation, leaching, and soil weathering limit nutrient availability in these ecosystems. Phosphorus (P) is a key element limiting net primary production, and in some areas, including forests recovering from prior disturbance, nitrogen (N) also may limit some components of production. Here we quantified atmospheric P and N inputs to these forests from fires using satellite-derived estimates of emissions and atmospheric models. In Africa and South America, cross-biome transport of fire-emitted aerosols and reactive N gases from savannas and areas near the deforestation frontier increased deposition of P and N in interior forests. Equatorward atmospheric transport during the dry (fire) season in one hemisphere was linked with surface winds moving toward the inter-tropical convergence zone (ITCZ) in the other hemisphere. Deposition levels were higher in tropical forests in Africa than in South America because of large savanna areas with high levels of fire emissions in both southern and northern Africa. We conclude by describing a potential feedback loop by which equatorward transport of fire emissions, dust, and spores sustains the productivity of tropical forests. We specifically assessed evidence that savanna-to-forest atmospheric transport of nutrients increases forest productivity, height, and rates of evapotranspiration (ET). In parallel, we examined the degree to which increases in ET and surface roughness in tropical forests have the potential to strengthen several components of the Hadley circulation, including deep convection, equatorward return flow (near the surface), and the intensity of seasonal drought in the subtropics (thereby increasing fires). These interactions are important for understanding biogeochemical - climate interactions on millennial timescales and for quantifying how

  6. Surgical outcome of primary clipping for anterior circulation aneurysms of size 2 centimeters or larger.

    Science.gov (United States)

    Furtado, Sunil V; Saikiran, Narayanam A; Thakar, Sumit; Dadlani, Ravi; Mohan, Dilip; Aryan, Saritha; Hegde, Alangar S

    2014-07-01

    Aneurysms of the anterior circulation larger than 2cm have a complex relationship to the anterior skull base, requiring a multi-modality management approach. This retrospective study of 54 patients with such aneurysms who underwent clipping between 2001 and 2012 analyzes clinical and surgical data, aneurysm characteristics and correlates them with respect to the Glasgow outcome score at follow-up and immediate post-operative clinical status. Patients with an outcome score of 5 or 4 were categorized as "good", while those with score 3-1 were "poor". Fisher's exact test and paired T-test (p<0.5) were used to test statistical significance for discrete and continuous variables respectively. 44 (81.4%) patients had a good outcome. Patients with non-ophthalmic/paraclinoid aneurysms had significantly lower incidence of adverse intra-operative events (p=0.035). Patients older than 50 years (p=0.045), with adverse intra-operative events (p=0.015) and post-operative infarction (p<0.001) had a poor outcome compared to those younger than 50 years age and those without adverse intra-operative events or infarctions. The grouped age variable had maximum influence on patient outcome. Location and size of aneurysm did not have an overall impact on surgical outcome. There were 4 mortalities. Primary clipping of proximal non-cavernous aneurysms on the internal carotid artery is associated with adverse intra-operative events. A multi-modality treatment approach in these aneurysms should be individualized, more so in patients older than 50 years. Copyright © 2014 Elsevier B.V. All rights reserved.

  7. Simultaneous quantification of monoamine neurotransmitters and their biogenic metabolites intracellularly and extracellularly in primary neuronal cell cultures and in sub-regions of guinea pig brain

    DEFF Research Database (Denmark)

    Schou-Pedersen, Anne Marie Voigt; Hansen, Stine Normann; Tveden-Nyborg, Pernille

    2016-01-01

    In the present paper, we describe a validated chromatographic method for the simultaneous quantification of monoamine neurotransmitters and their biogenic metabolites intracellularly and extracellularly in primary neuronal cell culture and in sub-regions of the guinea pig brain. Electrochemical...... of intracellular and extracellular amounts of monoamine neurotransmitters and their metabolites in guinea pig frontal cortex and hippocampal primary neuronal cell cultures. Noradrenaline, dopamine and serotonin were found to be in a range from 0.31 to 1.7 pmol per 2 million cells intracellularly, but only...... the biogenic metabolites could be detected extracellularly. Distinct differences in monoamine concentrations were observed when comparing concentrations in guinea pig frontal cortex and cerebellum tissue with higher amounts of dopamine and its metabolites, 3,4-dihydroxyphenylacetic acid and homovanillic acid...

  8. Insulin induces a shift in lipid and primary carbon metabolites in a model of fasting-induced insulin resistance

    Science.gov (United States)

    Olmstead, Keedrian I.; La Frano, Michael R.; Fahrmann, Johannes; Grapov, Dmitry; Viscarra, Jose A.; Newman, John W.; Fiehn, Oliver; Crocker, Daniel E.; Filipp, Fabian V.; Ortiz, Rudy M.

    2017-01-01

    Introduction Prolonged fasting in northern elephant seals (NES) is characterized by a reliance on lipid metabolism, conservation of protein, and reduced plasma insulin. During early fasting, glucose infusion previously reduced plasma free fatty acids (FFA); however, during late-fasting, it induced an atypical elevation in FFA despite comparable increases in insulin during both periods suggestive of a dynamic shift in tissue responsiveness to glucose-stimulated insulin secretion. Objective To better assess the contribution of insulin to this fasting-associated shift in substrate metabolism. Methods We compared the responses of plasma metabolites (amino acids (AA), FFA, endocannabinoids (EC), and primary carbon metabolites (PCM)) to an insulin infusion (65 mU/kg) in early- and late-fasted NES pups (n = 5/group). Plasma samples were collected prior to infusion (T0) and at 10, 30, 60, and 120 min post-infusion, and underwent untargeted and targeted metabolomics analyses utilizing a variety of GC-MS and LC-MS technologies. Results In early fasting, the majority (72%) of metabolite trajectories return to baseline levels within 2 h, but not in late fasting indicative of an increase in tissue sensitivity to insulin. In late-fasting, increases in FFA and ketone pools, coupled with decreases in AA and PCM, indicate a shift toward lipolysis, beta-oxidation, ketone metabolism, and decreased protein catabolism. Conversely, insulin increased PCM AUC in late fasting suggesting that gluconeogenic pathways are activated. Insulin also decreased FFA AUC between early and late fasting suggesting that insulin suppresses triglyceride hydrolysis. Conclusion Naturally adapted tolerance to prolonged fasting in these mammals is likely accomplished by suppressing insulin levels and activity, providing novel insight on the evolution of insulin during a condition of temporary, reversible insulin resistance. PMID:28757815

  9. Effects of vitamin D metabolites on cellular Ca2+ and on Ca transport in primary cultures of bone cells.

    Science.gov (United States)

    Eilam, Y; Szydel, N; Harell, A

    1980-09-01

    Both 1,25-dihydroxycholecalciferol (1,25(OH)2D3) and 24,25-dihydroxycholecalciferol (24,25(OH)2D3) exerted direct effects on Ca2+ transport and accumulation in primary cultures of bone cells. The following changes were recorded. (1) A significant decrease in the amount of intracellular exchangeable Ca2+. (2) A marked increase in the rate constants of efflux from the 'slow'-turnover intracellular Ca pool. (3) A marked increase in the 'initial rate' of Ca influx into the cells. Thus, vitamin D metabolites caused an increase in the turnover of Ca2+ in bone cells and altered the steady-stae level of intracellular exchangeable Ca2+. Whereas the changes in the rate of efflux were abolished in the presence of inhibitors of protein synthesis, the increase in the rate of influx was not sensitive to these inhibitors. It is suggested that the changes in the two fluxes were mediated by different mechanisms and that the changes in influx were due to a direct effect of vitamin D metabolites on the cellular membranes.

  10. Accumulation of primary and secondary metabolites in edible jackfruit seed tissues and scavenging of reactive nitrogen species.

    Science.gov (United States)

    Fernandes, Fátima; Ferreres, Federico; Gil-Izquierdo, Angel; Oliveira, Andreia P; Valentão, Patrícia; Andrade, Paula B

    2017-10-15

    Studies involving jackfruit tree (Artocarpus heterophyllus Lam.) focus on its fruit. Nevertheless a considerable part of jackfruit weight is represented by its seeds. Despite being consumed in several countries, knowledge about the chemical composition of these seeds is scarce. In this work, the accumulation of primary and secondary metabolites in jackfruit seed kernel and seed coating membrane was studied. Sixty-seven compounds were identified, sixty of them being reported for the first time in jackfruit seed. Both tissues had a similar qualitative profile, but significant quantitative differences were found. The capacity of aqueous extracts from jackfruit seed kernel and seed coating membranes to scavenge nitric oxide radical was also evaluated for the first time, the extract prepared from the seed coating membrane being the most potent. This work increases the potential revenue from a food that is still largely wasted. Copyright © 2017 Elsevier Ltd. All rights reserved.

  11. Changes in primary metabolites and polyphenols in the peel of "Braeburn" apples (Malus domestica Borkh.) during advanced maturation.

    Science.gov (United States)

    Bizjak, Jan; Mikulic-Petkovsek, Maja; Stampar, Franci; Veberic, Robert

    2013-10-30

    During the two growing seasons the evolution of primary metabolites and wide range of polyphenols in the "Braeburn" apple peel during advanced maturation were investigated. During the five weeks sucrose significantly increased, whereas fructose and glucose fluctuated around the same level in one season and decreased in another. Regarding malic and citric acids, an expected decrease was recorded. The concentrations of hydroxycinnamic acids, dihydrochalcones, and flavanols remained quite constant or slightly decreased during advanced apple ripening. On the contrary an intensive accumulation of quercetin glycosides and anthocyanins took place during this period, starting with the onset of rapid formation approximately 3 weeks before the technological maturity of apples. Total phenolic content was relatively constant or slightly increased. The present results suggest that measures designed to improve the apple color and quality of "Braeburn" apples should be performed approximately 3-4 weeks before the expected technological maturity of apples.

  12. The elimination rates of intact GIP as well as its primary metabolite, GIP 3-42, are similar in type 2 diabetic patients and healthy subjects

    DEFF Research Database (Denmark)

    Vilsbøll, Tina; Agersø, Henrik; Lauritsen, Torsten

    2006-01-01

    in the two groups and ranged from 8 to 21 l per subject. The primary metabolite, GIP 3-42, generated through the action of dipeptidyl peptidase IV (DPP-IV), was eliminated with a mean half-life of 17.5 and 20.5 min in patients and healthy subjects (NS). CONCLUSION: Elimination of GIP is similar in obese type...... 2 diabetic patients and matched healthy subjects. Differences in elimination of GIP and its primary metabolite, therefore, do not seem to contribute to the defective insulinotropic effect of GIP in type 2 diabetes....

  13. Effect of adrenomedullin on the cerebral circulation: relevance to primary headache disorders

    DEFF Research Database (Denmark)

    Petersen, K A; Birk, S; Kitamura, K

    2009-01-01

    Adrenomedullin (ADM) is closely related to calcitonin gene-related peptide, which has a known causative role in migraine. Animal studies have strongly suggested that ADM has a vasodilatory effect within the cerebral circulation. For these reasons, ADM is also likely to be involved in migraine....... However, the hypothetical migraine-inducing property and effect on human cerebral circulation of ADM have not previously been investigated. Human ADM (0.08 microg kg(-1) min(-1)) or placebo (saline 0.9%) was administered as a 20-min intravenous infusion to 12 patients suffering from migraine without aura...... in a crossover double-blind study. The occurrence of headache and associated symptoms were registered regularly 24 h post infusion. Cerebral blood flow (CBF) was measured by (133)Xenon single-photon emission computed tomography, mean blood flow velocity in the middle cerebral artery (V(MCA)) by transcranial...

  14. Calculation models of pressure wave propagation within the WWER-440 primary circulating loop

    International Nuclear Information System (INIS)

    Adamik, V.; Tkach, A.

    1982-01-01

    Computer codes SHOCK, LOVE, BAREL are described that can be used for the study of pressure wave propagation within the reactor and pipeline system during a LOCA as well as for mechanical loads identification in various parts of the system. SHOCK code is applicable to one-dimensional pressure wave propagation analysis in any hydraulic network containing a compressible nonviscous liquid with a constant (within the considered transient process period) density. LOVE code allows to calculate non-symmetrical mechanical loads on the WWER shaft in case of the main circulation pipeline cold branch rupture. BAREL code is an advanced modification of SHOCK code. It is fitted for two-dimensional pressure wave propagation analysing in the downstream section of a pressurised water reactor in case of the main circulation pipeline cold branch rupture. The calculation results for B-213 type WWER-440 reactor are presented that have been obtained under the assumption of perfect structure rigidity [ru

  15. GC-MS metabolic profiling of Cabernet Sauvignon and Merlot cultivars during grapevine berry development and network analysis reveals a stage- and cultivar-dependent connectivity of primary metabolites.

    Science.gov (United States)

    Cuadros-Inostroza, Alvaro; Ruíz-Lara, Simón; González, Enrique; Eckardt, Aenne; Willmitzer, Lothar; Peña-Cortés, Hugo

    Information about the total chemical composition of primary metabolites during grape berry development is scarce, as are comparative studies trying to understand to what extent metabolite modifications differ between cultivars during ripening. Thus, correlating the metabolic profiles with the changes occurring in berry development and ripening processes is essential to progress in their comprehension as well in the development of new approaches to improve fruit attributes. Here, the developmental metabolic profiling analysis across six stages from flowering to fully mature berries of two cultivars, Cabernet Sauvignon and Merlot, is reported at metabolite level. Based on a gas chromatography-mass spectrometry untargeted approach, 115 metabolites were identified and relative quantified in both cultivars. Sugars and amino acids levels show an opposite behaviour in both cultivars undergoing a highly coordinated shift of metabolite associated to primary metabolism during the stages involved in growth, development and ripening of berries. The changes are characteristic for each stage, the most pronounced ones occuring at fruit setting and pre-Veraison. They are associated to a reduction of the levels of metabolites present in the earlier corresponding stage, revealing a required catabolic activity of primary metabolites for grape berry developmental process. Network analysis revealed that the network connectivity of primary metabolites is stage- and cultivar-dependent, suggesting differences in metabolism regulation between both cultivars as the maturity process progresses. Furthermore, network analysis may represent an appropriate method to display the association between primary metabolites during berry developmental processes among different grapevine cultivars and for identifying potential biologically relevant metabolites.

  16. 3. Workshop for IAEA ICSP on Integral PWR Design Natural Circulation Flow Stability and Thermo-hydraulic Coupling of Containment and Primary System during Accidents. Presentations

    International Nuclear Information System (INIS)

    2012-04-01

    Most advanced nuclear power plant designs adopted several kinds of passive systems. Natural circulation is used as a key driving force for many passive systems and even for core heat removal during normal operation such as NuScale, CAREM, ESBWR and Indian AHWR designs. Simulation of natural circulation phenomena is very challenging since the driving force of it is weak compared to forced circulation and involves a coupling between primary system and containment for integral type reactor. The IAEA ICSP (International Collaborative Standard Problem) on 'Integral PWR Design Natural Circulation Flow Stability and Thermo-hydraulic Coupling of Containment and Primary System during Accidents' was proposed within the CRP on 'Natural Circulation Phenomena, Modelling, and Reliability of Passive Systems that utilize Natural Circulation'. Oregon State University (OSU) of USA offered to host this ICSP. This ICSP plans to conduct the following experiments and blind/open simulations with system codes: 1. Quasi-steady state operation with different core power levels: Conduct quasi-steady state operation with step-wise increase of core power level in order to observe single phase natural circulation flow according to power level. The experimental facility and operating conditions for an integral PWR will be used. 2. Thermo-hydraulic Coupling between Primary system and Containment: Conduct a loss of feedwater transient with subsequent ADS blowdown and long term cooling to determine the progression of a loss of feedwater transient by natural circulation through primary and containment systems. These tests would examine the blowdown phase as well as the long term cooling using sump natural circulation by coupling the primary to containment systems. This data could be used for the evaluation of system codes to determine if they model specific phenomena in an accurate manner. OSU completed planned two ICSP tests in July 2011 and real initial and boundary conditions measured from the

  17. CFD Analysis of the Primary Cooling System for the Small Modular Natural Circulation Lead Cooled Fast Reactor SNRLFR-100

    Directory of Open Access Journals (Sweden)

    Pengcheng Zhao

    2016-01-01

    Full Text Available Small modular reactor (SMR has drawn wide attention in the past decades, and Lead cooled fast reactor (LFR is one of the most promising advanced reactors which are able to meet the safety economic goals of Gen-IV nuclear energy systems. A small modular natural circulation lead cooled fast reactor-100 MWth (SNRLFR-100 is being developed by University of Science and Technology of China (USTC. In the present work, a 3D CFD model, primary heat exchanger model, fuel pin model, and point kinetic model were established based on some reasonable simplifications and assumptions, the steady-state natural circulation characteristics of SNCLFR-100 primary cooling system were discussed and illustrated, and some reasonable suggestions were proposed for the reactor’s thermal-hydraulic and structural design. Moreover, in order to have a first evaluation of the system behavior in accident conditions, an unprotected loss of heat sink (ULOHS transient simulation at beginning of the reactor cycle (BOC has been analyzed and discussed based on the steady-state simulation results. The key temperatures of the reactor core are all under the safety limits at transient state; the reactor has excellent thermal-hydraulic performance.

  18. Familial Resemblance for Serum Metabolite Concentrations

    NARCIS (Netherlands)

    Draisma, H.H.M.; Beekman, M.; Pool, R.; van Ommen, G.J.B; Vaarhorst, A.A.M.; de Craen, A.J.; Willemsen, G.; Slagboom, P.E.; Boomsma, D.I.

    2013-01-01

    Metabolomics is the comprehensive study of metabolites, which are the substrates, intermediate, and end products of cellular metabolism. The heritability of the concentrations of circulating metabolites bears relevance for evaluating their suitability as biomarkers for disease. We report aspects of

  19. ABA and GA3 regulate the synthesis of primary and secondary metabolites related to alleviation from biotic and abiotic stresses in grapevine.

    Science.gov (United States)

    Murcia, Germán; Fontana, Ariel; Pontin, Mariela; Baraldi, Rita; Bertazza, Gianpaolo; Piccoli, Patricia N

    2017-03-01

    Plants are able to synthesize a large number of organic compounds. Among them, primary metabolites are known to participate in plant growth and development, whereas secondary metabolites are mostly involved in defense and other facultative processes. In grapevine, one of the major fruit crops in the world, secondary metabolites, mainly polyphenols, are of great interest for the wine industry. Even though there is an extensive literature on the content and profile of those compounds in berries, scarce or no information is available regarding polyphenols in other organs. In addition, little is known about the effect of plant growth regulators (PGRs), ABA and GA 3 (extensively used in table grapes) on the synthesis of primary and secondary metabolites in wine grapes. In table grapes, cultural practices include the use of GA 3 sprays shortly before veraison, to increase berry and bunch size, and sugar content in fruits. Meanwhile, ABA applications to the berries on pre-veraison improve the skin coloring and sugar accumulation, anticipating the onset of veraison. Accordingly, the aim of this study was to assess and characterize primary and secondary metabolites in leaves, berries and roots of grapevine plants cv. Malbec at veraison, and changes in compositions after ABA and GA 3 aerial sprayings. Metabolic profiling was conducted using GC-MS, GC-FID and HPLC-MWD. A large set of metabolites was identified: sugars, alditols, organic acids, amino acids, polyphenols (flavonoids and non-flavonoids) and terpenes (mono-, sesqui-, di- and triterpenes). The obtained results showed that ABA applications elicited synthesis of mono- and sesquiterpenes in all assessed tissues, as well as L-proline, acidic amino acids and anthocyanins in leaves. Additionally, applications with GA 3 elicited synthesis of L-proline in berries, and mono- and sesquiterpenes in all the tissues. However, treatment with GA 3 seemed to block polyphenol synthesis, mainly in berries. In conclusion, ABA and GA

  20. Steroid replacement in primary adrenal failure does not appear to affect circulating adipokines

    OpenAIRE

    Fichna, Marta; Fichna, Piotr; Gryczy?ska, Maria; Czarnywojtek, Agata; ?urawek, Magdalena; Rucha?a, Marek

    2014-01-01

    Despite continuous efforts for an optimal steroid replacement, recent observations suggest increased cardiometabolic risk and related mortality in primary adrenal insufficiency (PAI). Adipokines are peptides from the adipose tissue, markers of cardiometabolic dysfunction. This study was aimed to evaluate serum levels of adipokines: leptin, adiponectin, and resistin in PAI during conventional steroid substitution. The analysis comprised 63 patients (mean age 42.7???14.1?years) and 63 healthy c...

  1. Volatiles and primary metabolites profiling in two Hibiscus sabdariffa (roselle) cultivars via headspace SPME-GC-MS and chemometrics.

    Science.gov (United States)

    Farag, Mohamed A; Rasheed, Dalia M; Kamal, Islam M

    2015-12-01

    Hibiscus sabdariffa (roselle) is a plant of considerable commercial importance worldwide as functional food due to its organic acids, mucilage, anthocyanins, macro and micro-nutrients content. Although Hibiscus flowers are emerging as very competitive targets for phytochemical studies, very little is known about their volatile composition and or aroma, such knowledge can be suspected to be relevant for understanding its olfactory and taste properties. To provide insight into Hibiscus flower aroma composition and for its future use in food and or pharmaceutical industry, volatile constituents from 2 cultivars grown in Egypt, viz. Aswan and Sudan-1 were profiled using solid-phase microextraction (SPME) coupled to GCMS. A total of 104 volatiles were identified with sugar and fatty acid derived volatiles amounting for the major volatile classes. To reveal for cultivar effect on volatile composition in an untargeted manner, multivariate data analysis was applied. Orthogonal projection to latent structures-discriminant analysis (OPLS-DA) revealed for 1-octen-3-ol versus furfural/acetic acid enrichment in Aswan and Sudan-1 cvs., respectively. Primary metabolites contributing to roselle taste and nutritional value viz. sugars and organic acids were profiled using GC-MS after silylation. The impact of probiotic bacteria on roselle infusion aroma profile was further assessed and revealed for the increase in furfural production with Lactobacillus plantarum inoculation and without affecting its anthocyanin content. This study provides the most complete map for volatiles, sugars and organic acids distribution in two Hibiscus flower cultivars and its fermented product. Copyright © 2015 Elsevier Ltd. All rights reserved.

  2. Glutamate-Mediated Primary Somatosensory Cortex Excitability Correlated with Circulating Copper and Ceruloplasmin

    Directory of Open Access Journals (Sweden)

    Franca Tecchio

    2011-01-01

    Full Text Available Objective. To verify whether markers of metal homeostasis are related to a magnetoencephalographic index representative of glutamate-mediated excitability of the primary somatosensory cortex. The index is identified as the source strength of the earliest component (M20 of the somatosensory magnetic fields (SEFs evoked by right median nerve stimulation at wrist. Method. Thirty healthy right-handed subjects (51±22 years were enrolled in the study. A source reconstruction algorithm was applied to assess the amount of synchronously activated neurons subtending the M20 and the following SEF component (M30, which is generated by two independent contributions of gabaergic and glutamatergic transmission. Serum copper, ceruloplasmin, iron, transferrin, transferrin saturation, and zinc levels were measured. Results. Total copper and ceruloplasmin negatively correlated with the M20 source strength. Conclusion. This pilot study suggests that higher level of body copper reserve, as marked by ceruloplasmin variations, parallels lower cortical glutamatergic responsiveness.

  3. Steroid replacement in primary adrenal failure does not appear to affect circulating adipokines.

    Science.gov (United States)

    Fichna, Marta; Fichna, Piotr; Gryczyńska, Maria; Czarnywojtek, Agata; Żurawek, Magdalena; Ruchała, Marek

    2015-03-01

    Despite continuous efforts for an optimal steroid replacement, recent observations suggest increased cardiometabolic risk and related mortality in primary adrenal insufficiency (PAI). Adipokines are peptides from the adipose tissue, markers of cardiometabolic dysfunction. This study was aimed to evaluate serum levels of adipokines: leptin, adiponectin, and resistin in PAI during conventional steroid substitution. The analysis comprised 63 patients (mean age 42.7 ± 14.1 years) and 63 healthy controls. Serum adipokines, lipid profile, and plasma glucose were assessed in both cohorts. ACTH, serum insulin, HOMA-IR, DHEA-S, cortisol and 24 h urinary free cortisol were determined in PAI. Body mass composition was analyzed by Dual-Energy X-ray Absorptiometry. Mean BMI in the control group was 24.1 ± 3.9 kg/m(2) and 23.7 ± 3.9 kg/m(2) in the PAI cohort. Serum leptin and adiponectin levels were similar in both groups, whereas resistin appeared significantly lower among affected subjects (p = 0.0002). Its levels were weakly correlated with HOMA-IR (p = 0.048). Leptin was independently correlated with fasting insulin, HOMA-IR, BMI, and body fat (p regression analysis only weight (p = 0.017), total and HDL cholesterol (p replacement. Serum adipokines in treated PAI follow similar correlations to those reported in healthy subjects. Further prospective studies are warranted to verify and explain plausible excess of cardiovascular mortality in PAI.

  4. Interaction and Transport of Methamphetamine and its Primary Metabolites by Organic Cation and Multidrug and Toxin Extrusion Transporters.

    Science.gov (United States)

    Wagner, David J; Sager, Jennifer E; Duan, Haichuan; Isoherranen, Nina; Wang, Joanne

    2017-07-01

    Methamphetamine is one of the most abused illicit drugs with roughly 1.2 million users in the United States alone. A large portion of methamphetamine and its metabolites is eliminated by the kidney with renal clearance larger than glomerular filtration clearance. Yet the mechanism of active renal secretion is poorly understood. The goals of this study were to characterize the interaction of methamphetamine and its major metabolites with organic cation transporters (OCTs) and multidrug and toxin extrusion (MATE) transporters and to identify the major transporters involved in the disposition of methamphetamine and its major metabolites, amphetamine and para -hydroxymethamphetamine ( p -OHMA). We used cell lines stably expressing relevant transporters to show that methamphetamine and its metabolites inhibit human OCTs 1-3 (hOCT1-3) and hMATE1/2-K with the greatest potencies against hOCT1 and hOCT2. Methamphetamine and amphetamine are substrates of hOCT2, hMATE1, and hMATE2-K, but not hOCT1 and hOCT3. p -OHMA is transported by hOCT1-3 and hMATE1, but not hMATE2-K. In contrast, organic anion transporters 1 and 3 do not interact with or transport these compounds. Methamphetamine and its metabolites exhibited complex interactions with hOCT1 and hOCT2, suggesting the existence of multiple binding sites. Our studies suggest the involvement of the renal OCT2/MATE pathway in tubular secretion of methamphetamine and its major metabolites and the potential of drug-drug interactions with substrates or inhibitors of the OCTs. This information may be considered when prescribing medications to suspected or known abusers of methamphetamine to mitigate the risk of increased toxicity or reduced therapeutic efficacy. Copyright © 2017 by The American Society for Pharmacology and Experimental Therapeutics.

  5. Simultaneous quantification of monoamine neurotransmitters and their biogenic metabolites intracellularly and extracellularly in primary neuronal cell cultures and in sub-regions of guinea pig brain.

    Science.gov (United States)

    Schou-Pedersen, Anne Marie V; Hansen, Stine N; Tveden-Nyborg, Pernille; Lykkesfeldt, Jens

    2016-08-15

    In the present paper, we describe a validated chromatographic method for the simultaneous quantification of monoamine neurotransmitters and their biogenic metabolites intracellularly and extracellularly in primary neuronal cell culture and in sub-regions of the guinea pig brain. Electrochemical detection provided limits of quantifications (LOQs) between 3.6 and 12nM. Within the linear range, obtained recoveries were from 90.9±9.9 to 120±14% and intra-day and inter-day precisions found to be less than 5.5% and 12%, respectively. The analytical method was applicable for quantification of intracellular and extracellular amounts of monoamine neurotransmitters and their metabolites in guinea pig frontal cortex and hippocampal primary neuronal cell cultures. Noradrenaline, dopamine and serotonin were found to be in a range from 0.31 to 1.7pmol per 2 million cells intracellularly, but only the biogenic metabolites could be detected extracellularly. Distinct differences in monoamine concentrations were observed when comparing concentrations in guinea pig frontal cortex and cerebellum tissue with higher amounts of dopamine and its metabolites, 3,4-dihydroxyphenylacetic acid and homovanillic acid in frontal cortex, as compared to cerebellum. The chemical turnover in frontal cortex tissue of guinea pig was for serotonin successfully predicted from the turnover observed in the frontal cortex cell culture. In conclusion, the present analytical method shows high precision, accuracy and sensitivity and is broadly applicable to monoamine measurements in cell cultures as well as brain biopsies from animal models used in preclinical neurochemistry. Copyright © 2016 Elsevier B.V. All rights reserved.

  6. Measurement of caffeine and its three primary metabolites in human plasma by HPLC-ESI-MS/MS and clinical application.

    Science.gov (United States)

    Chen, Feng; Hu, Zhe-Yi; Parker, Robert B; Laizure, S Casey

    2017-06-01

    Caffeine is a mild stimulant with significant potential for abuse, being consumed in larger doses with the widespread availability of energy drinks and by novel routes of administration such as inspired powder, oral sprays and electronic cigarettes. How these recent changes in caffeine consumption affecting caffeine disposition and abuse potential is of growing concern. In the study of caffeine disposition in humans, it is common to only measure the caffeine concentration; however, caffeine's three major metabolites (paraxanthine, theobromine and theophylline) retain central nervous system stimulant activity that may contribute to the overall pharmacological activity and toxicity. Therefore, it would be scientifically more rigorous to measure caffeine and its major metabolites in the evaluation of caffeine disposition in human subjects. Herein, we report a method for the simultaneous quantification of caffeine and its three major metabolites in human plasma by high-performance liquid chromatography coupled to electrospray tandem mass spectrometry (HPLC-ESI-MS/MS). Human plasma samples were treated by simple protein precipitation and the analytes were separated using a 6 min gradient program. Precision and accuracy were well within in the 15% acceptance range. The simple sample preparation, short runtime, sensitivity and the inclusion of caffeine's major metabolites make this assay methodology optimal for the study of caffeine's pharmacokinetics and pharmacodynamics in human subjects. Copyright © 2016 John Wiley & Sons, Ltd.

  7. Print Capitalism, New School and Circulation of Reading Models. A Brazilian Collection at the Primary Education Museum-Library in Portugal (1931-1950)

    Science.gov (United States)

    Toledo, Maria Rita Almeida; Carvalho, Marta Maria Chagas

    2011-01-01

    The present article is the fruit of research on the circulation of Brazilian books from the "Atualidades Pedagogicas" collection at the "Biblioteca Museu do Ensino Primario" (Primary Education Museum-Library) in Lisbon. This library was headed by Adolfo Lima, one of the exponents of the Portuguese New School, and gave form to…

  8. Mass Spectrometric Characterization of Circulating Covalent Protein Adducts Derived from a Drug Acyl Glucuronide Metabolite: Multiple Albumin Adductions in Diclofenac Patients

    Science.gov (United States)

    Hammond, Thomas G.; Meng, Xiaoli; Jenkins, Rosalind E.; Maggs, James L.; Castelazo, Anahi Santoyo; Regan, Sophie L.; Bennett, Stuart N. L.; Earnshaw, Caroline J.; Aithal, Guruprasad P.; Pande, Ira; Kenna, J. Gerry; Stachulski, Andrew V.; Park, B. Kevin

    2014-01-01

    Covalent protein modifications by electrophilic acyl glucuronide (AG) metabolites are hypothetical causes of hypersensitivity reactions associated with certain carboxylate drugs. The complex rearrangements and reactivities of drug AG have been defined in great detail, and protein adducts of carboxylate drugs, such as diclofenac, have been found in liver and plasma of experimental animals and humans. However, in the absence of definitive molecular characterization, and specifically, identification of signature glycation conjugates retaining the glucuronyl and carboxyl residues, it cannot be assumed any of these adducts is derived uniquely or even fractionally from AG metabolites. We have therefore undertaken targeted mass spectrometric analyses of human serum albumin (HSA) isolated from diclofenac patients to characterize drug-derived structures and, thereby, for the first time, have deconstructed conclusively the pathways of adduct formation from a drug AG and its isomeric rearrangement products in vivo. These analyses were informed by a thorough understanding of the reactions of HSA with diclofenac AG in vitro. HSA from six patients without drug-related hypersensitivities had either a single drug-derived adduct or one of five combinations of 2–8 adducts from among seven diclofenac N-acylations and three AG glycations on seven of the protein’s 59 lysines. Only acylations were found in every patient. We present evidence that HSA modifications by diclofenac in vivo are complicated and variable, that at least a fraction of these modifications are derived from the drug’s AG metabolite, and that albumin adduction is not inevitably a causation of hypersensitivity to carboxylate drugs or a coincidental association. PMID:24902585

  9. Evaluation of Two Different Analytical Methods for Circulating Tumor Cell Detection in Peripheral Blood of Patients with Primary Breast Cancer

    Directory of Open Access Journals (Sweden)

    B. A. S. Jaeger

    2014-01-01

    Full Text Available Background. Evidence is accumulating that circulating tumor cells (CTC out of peripheral blood can serve as prognostic marker not only in metastatic but also in early breast cancer (BC. Various methods are available to detect CTC. Comparisons between the different techniques, however, are rare. Material and Methods. We evaluate two different methods for CTC enrichment and detection in primary BC patients: the FDA-approved CellSearch System (CSS; Veridex, Warren, USA and a manual immunocytochemistry (MICC. The cut-off value for positivity was ≥1 CTC. Results. The two different nonoverlapping patient cohorts evaluated with one or the other method were well balanced regarding common clinical parameters. Before adjuvant CHT 21.1% (416 out of 1972 and 20.6% (247 out of 1198 of the patients were CTC-positive, while after CHT 22.5% (359 out of 1598 and 16.6% (177 out of 1066 of the patients were CTC-positive using CSS or MICC, respectively. CTC positivity rate before CHT was thus similar and not significantly different (P=0.749, while CTC positivity rate immediately after CHT was significantly lower using MICC compared to CSS (P<0.001. Conclusion. Using CSS or MICC for CTC detection, we found comparable prevalence of CTC before but not after adjuvant CHT.

  10. Metabolism of pentachlorophenol in cell suspension cultures of wheat (Triticum aestivum L.). Tetrachlorocatechol as a primary metabolite

    International Nuclear Information System (INIS)

    Schaefer, W.; Sandermann, H. Jr.

    1988-01-01

    Wheat cell suspension cultures were incubated with [U- 14 C] pentachlorophenol (PCP; 1 ppm, 48 h, 27 0 C). Soluble metabolites were formed in ∼ 50% yield, another ∼ 31% of the applied radioactivity being incorporated into the insoluble residue. The soluble metabolite fraction, and its β-D-glucoside conjugate components, the total insoluble residue, and its lignin components, were all found to contain a novel polar PCP derivative besides smaller amounts of tetrachlorohydroquinone and PCP. The novel derivative also predominated in intact wheat plants and was identified as tetrachlorocatechol by TLC, HPLC, GC, and EI as well as CI mass spectroscopy. Tetrachlorocatechol is a potential mutagen, so that the soluble and insoluble conjugates formed in wheat from PCP may present a toxicological hazard

  11. Metabolism of N-methylformamide in mice: primary kinetic deuterium isotope effect and identification of S-(N-methylcarbamoyl)glutathione as a metabolite

    International Nuclear Information System (INIS)

    Threadgill, M.D.; Axworthy, D.B.; Baillie, T.A.; Farmer, P.B.; Farrow, K.C.; Gescher, A.; Kestell, P.; Pearson, P.G.; Shaw, A.J.

    1987-01-01

    S-(N-Methylcarbamoyl)glutathione has been identified by cesium ion liquid secondary ion mass spectrometry as a biliary metabolite in mice of the experimental antitumor agent and hepatotoxin N-methylformamide. Metabolism of N-methylformamide to urinary methylamine, urinary N-acetyl-S-(N-methylcarbamoyl)-cysteine and biliary S-(N-methylcarbamoyl)glutathione was found to be subject to large intermolecular primary kinetic isotope effects when hydrogen was replaced by deuterium in the formyl group (kH/kD = 5.5 +/- 0.2, 4.5 +/- 1.0 and 7 +/- 2, respectively), as shown by mass spectrometry of derivatives of these metabolites. These values indicate the existence of a common metabolic precursor for each of these metabolites. In particular, methylamine is shown not to arise from simple enzymatic hydrolysis of N-methylformamide but is associated with an oxidative process. Therefore, it is highly likely that N-methylformamide is oxidized and conjugated to form S-(N-methylcarbamoyl)glutathione which is metabolized further to N-acetyl-S-(N-methylcarbamoyl) cysteine. Either of these thiocarbamates could be hydrolyzed to give the parent thiol and the observed metabolic end products, methylamine and carbon dioxide. The presence of deuterium in the formyl moiety of N-methylformamide reduced markedly the hepatotoxicity of the compound, as shown by measurements of the activities of appropriate hepatic enzymes in plasma

  12. Primary, Secondary Metabolites, H2O2, Malondialdehyde and Photosynthetic Responses of Orthosiphon stimaneus Benth. to Different Irradiance Levels

    Directory of Open Access Journals (Sweden)

    Mohd Hafiz Ibrahim

    2012-01-01

    Full Text Available The resource availability hypothesis predicts an increase in the allocation to secondary metabolites when carbon gain is improved relative to nutrient availability, which normally occurs during periods of low irradiance. The present work was carried out to confirm this hypothesis by investigating the effects of decreasing irradiance on the production of plant secondary metabolites (flavonoids and phenolics in the herbal plant Orthosiphon stamineus, and to characterize this production by carbohydrate, H2O2, and malondialdehyde (MDA levels, net photosynthesis, leaf chlorophyll content and carbon to nitrogen ratio (C/N. Four levels of irradiance (225, 500, 625 and 900 µmol/m2/s were imposed onto two-week old seedlings for 12 weeks in a randomized complete block design experiment. Peak production of total flavonoids, phenolics, soluble sugar, starch and total non-structural carbohydrate ocurred under low irradiance of 225 µmol/m2/s, and decreased with increasing irradiance. The up-regulation of secondary metabolites could be explained by the concomitant increases in H2O2 and MDA activities under low irradiance. This condition also resulted in enhanced C/N ratio signifying a reduction in nitrogen levels, which had established significant negative correlations with net photosynthesis, total biomass and total chlorophyll content, indicating the possible existence of a trade-off between growth and secondary metabolism under low irradiance with reduced nitrogen content. The competition between total chlorophyll and secondary metabolites production, as exhibited by the negative correlation coefficient under low irradiance, also suggests a sign of gradual switch of investment from chlorophyll to polyphenols production.

  13. Fueling primary productivity: nutrient return pathways from the deep ocean and their dependence on the Meridional Overturning Circulation

    Science.gov (United States)

    Palter, J. B.; Sarmiento, J. L.; Gnanadesikan, A.; Simeon, J.; Slater, D.

    2010-06-01

    In the Southern Ocean, mixing and upwelling in the presence of heat and freshwater surface fluxes transform subpycnocline water to lighter densities as part of the upward branch of the Meridional Overturning Circulation (MOC). One hypothesized impact of this transformation is the restoration of nutrients to the global pycnocline, without which biological productivity at low latitudes would be catastrophically reduced. Here we use a novel set of modeling experiments to explore the causes and consequences of the Southern Ocean nutrient return pathway. Specifically, we quantify the contribution to global productivity of nutrients that rise from the ocean interior in the Southern Ocean, the northern high latitudes, and by mixing across the low latitude pycnocline. In addition, we evaluate how the strength of the Southern Ocean winds and the parameterizations of subgridscale processes change the dominant nutrient return pathways in the ocean. Our results suggest that nutrients upwelled from the deep ocean in the Antarctic Circumpolar Current and subducted in Subantartic Mode Water support between 33 and 75% of global primary productivity between 30° S and 30° N. The high end of this range results from an ocean model in which the MOC is driven primarily by wind-induced Southern Ocean upwelling, a configuration favored due to its fidelity to tracer data, while the low end results from an MOC driven by high diapycnal diffusivity in the pycnocline. In all models, the high preformed nutrients subducted in the SAMW layer are converted rapidly (in less than 40 years) to remineralized nutrients, explaining previous modeling results that showed little influence of the drawdown of SAMW surface nutrients on atmospheric carbon concentrations.

  14. Investigation of circulating temperature fluctuations of the primary coolant in order to develop an enhanced MTC estimator for VVER-440 reactors

    Energy Technology Data Exchange (ETDEWEB)

    Kiss, Sandor; Lipcsei, Sandor [Hungarian Academy of Sciences, Budapest (Hungary). Centre for Energy Research - MTA

    2017-09-15

    Our aim was to develop a method based on noise diagnostics for the estimation of the moderator temperature coefficient of reactivity (MTC) for the Paks VVER-440 units in normal operation. The method requires determining core average neutron flux and temperature fluctuations. The circulation period of the primary coolant, transfer properties of the steam generators, as well as the source and the propagation of the temperature perturbations and the proportions of the perturbation components were investigated in order to estimate the feedback caused by the circulation of the primary coolant. Finally, after developing the new MTC estimator, determining its frequency range and optimal parameters, trends were produced based on an overall evaluation of measurements made with standard instrumentation during a one-year-long period at Paks NPP.

  15. Polycyclic aromatic acids are primary metabolites of alkyl-PAHs - a case study with Nereis diversicolor

    DEFF Research Database (Denmark)

    Malmquist, Linus Mattias Valdemar; Selck, Henriette; Jørgensen, Kåre Bredeli

    2015-01-01

    Although concentrations of alkylated polycyclic aromatic hydrocarbons (alkyl-PAHs) in oil-contaminated sediments are higher than those of unsubstituted PAHs, only little attention has been given to metabolism and ecotoxicity of alkyl-PAHs. In this study we demonstrated that metabolism of alkyl-PA...... that carboxylic acid metabolites of alkyl-PAHs have the potential of constituting a new class of contaminants in marine waters that needs attention in relation to ecological risk assessments.......Although concentrations of alkylated polycyclic aromatic hydrocarbons (alkyl-PAHs) in oil-contaminated sediments are higher than those of unsubstituted PAHs, only little attention has been given to metabolism and ecotoxicity of alkyl-PAHs. In this study we demonstrated that metabolism of alkyl...

  16. Glucose feeds the TCA cycle via circulating lactate.

    Science.gov (United States)

    Hui, Sheng; Ghergurovich, Jonathan M; Morscher, Raphael J; Jang, Cholsoon; Teng, Xin; Lu, Wenyun; Esparza, Lourdes A; Reya, Tannishtha; Le Zhan; Yanxiang Guo, Jessie; White, Eileen; Rabinowitz, Joshua D

    2017-11-02

    Mammalian tissues are fuelled by circulating nutrients, including glucose, amino acids, and various intermediary metabolites. Under aerobic conditions, glucose is generally assumed to be burned fully by tissues via the tricarboxylic acid cycle (TCA cycle) to carbon dioxide. Alternatively, glucose can be catabolized anaerobically via glycolysis to lactate, which is itself also a potential nutrient for tissues and tumours. The quantitative relevance of circulating lactate or other metabolic intermediates as fuels remains unclear. Here we systematically examine the fluxes of circulating metabolites in mice, and find that lactate can be a primary source of carbon for the TCA cycle and thus of energy. Intravenous infusions of 13 C-labelled nutrients reveal that, on a molar basis, the circulatory turnover flux of lactate is the highest of all metabolites and exceeds that of glucose by 1.1-fold in fed mice and 2.5-fold in fasting mice; lactate is made primarily from glucose but also from other sources. In both fed and fasted mice, 13 C-lactate extensively labels TCA cycle intermediates in all tissues. Quantitative analysis reveals that during the fasted state, the contribution of glucose to tissue TCA metabolism is primarily indirect (via circulating lactate) in all tissues except the brain. In genetically engineered lung and pancreatic cancer tumours in fasted mice, the contribution of circulating lactate to TCA cycle intermediates exceeds that of glucose, with glutamine making a larger contribution than lactate in pancreatic cancer. Thus, glycolysis and the TCA cycle are uncoupled at the level of lactate, which is a primary circulating TCA substrate in most tissues and tumours.

  17. Effects of methamphetamine and its primary human metabolite, p-hydroxymethamphetamine, on the development of the Australian blowfly Calliphora stygia.

    Science.gov (United States)

    Mullany, Christina; Keller, Paul A; Nugraha, Ari S; Wallman, James F

    2014-08-01

    The larvae of necrophagous fly species are used as forensic tools for the determination of the minimum postmortem interval (PMI). However, any ingested drugs in corpses may affect larval development, thus leading to incorrect estimates of the period of infestation. This study investigated the effects of methamphetamine and its metabolite, p-hydroxymethamphetamine, on the forensically important Australian blowfly Calliphora stygia. It was found that the presence of the drugs significantly accelerated larval growth and increased the size of all life stages. Furthermore, drug-exposed samples remained as pupae for up to 78 h longer than controls. These findings suggest that estimates of the minimum PMI of methamphetamine-dosed corpses could be incorrect if the altered growth of C. stygia is not considered. Different temperatures, drug concentrations and substrate types are also likely to affect the development of this blowfly. Pending further research, the application of C. stygia to the entomological analysis of methamphetamine-related fatalities should be appropriately qualified. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  18. Gene expression profiles in human and mouse primary cells provide new insights into the differential actions of vitamin D3 metabolites.

    Directory of Open Access Journals (Sweden)

    Pentti Tuohimaa

    Full Text Available 1α,25-Dihydroxyvitamin D3 (1α,25(OH2D3 had earlier been regarded as the only active hormone. The newly identified actions of 25-hydroxyvitamin D3 (25(OHD3 and 24R,25-dihydroxyvitamin D3 (24R,25(OH2D3 broadened the vitamin D3 endocrine system, however, the current data are fragmented and a systematic understanding is lacking. Here we performed the first systematic study of global gene expression to clarify their similarities and differences. Three metabolites at physiologically comparable levels were utilized to treat human and mouse fibroblasts prior to DNA microarray analyses. Human primary prostate stromal P29SN cells (hP29SN, which convert 25(OHD3 into 1α,25(OH2D3 by 1α-hydroxylase (encoded by the gene CYP27B1, displayed regulation of 164, 171, and 175 genes by treatment with 1α,25(OH2D3, 25(OHD3, and 24R,25(OH2D3, respectively. Mouse primary Cyp27b1 knockout fibroblasts (mCyp27b1 (-/-, which lack 1α-hydroxylation, displayed regulation of 619, 469, and 66 genes using the same respective treatments. The number of shared genes regulated by two metabolites is much lower in hP29SN than in mCyp27b1 (-/-. By using DAVID Functional Annotation Bioinformatics Microarray Analysis tools and Ingenuity Pathways Analysis, we identified the agonistic regulation of calcium homeostasis and bone remodeling between 1α,25(OH2D3 and 25(OHD3 and unique non-classical actions of each metabolite in physiological and pathological processes, including cell cycle, keratinocyte differentiation, amyotrophic lateral sclerosis signaling, gene transcription, immunomodulation, epigenetics, cell differentiation, and membrane protein expression. In conclusion, there are three distinct vitamin D3 hormones with clearly different biological activities. This study presents a new conceptual insight into the vitamin D3 endocrine system, which may guide the strategic use of vitamin D3 in disease prevention and treatment.

  19. Deletion of the signalling molecule synthase ScbA has pleiotropic effects on secondary metabolite biosynthesis, morphological differentiation and primary metabolism in Streptomyces coelicolor A3(2)

    NARCIS (Netherlands)

    D'Alia, Davide; Eggle, D.; Nieselt, K.; Hu, W.-S.; Breitling, R.; Takano, E.

    2011-01-01

    Streptomycetes have high biotechnological relevance as producers of diverse metabolites widely used in medical and agricultural applications. The biosynthesis of these metabolites is controlled by signalling molecules, gamma-butyrolactones, that act as bacterial hormones. In Streptomyces coelicolor,

  20. Snapping Turtles (Chelydra serpentina) from Canadian Areas of Concern across the southern Laurentian Great Lakes: Chlorinated and brominated hydrocarbon contaminants and metabolites in relation to circulating concentrations of thyroxine and vitamin A.

    Science.gov (United States)

    Letcher, Robert J; Lu, Zhe; de Solla, Shane R; Sandau, Courtney D; Fernie, Kimberly J

    2015-11-01

    The metabolites of polychlorinated biphenyls (PCBs) and polybrominated diphenyl ethers (PBDEs), as well as other halogenated phenolic contaminants (HPCs) have been shown to have endocrine-disrupting properties, and have been reported with increasing frequency in the blood of wildlife, and mainly in mammals and birds. However, little is known about the persistence, accumulation and distribution of these contaminants in long-lived freshwater reptiles. In the present study, in addition to a large suite of chlorinated and brominated contaminants, metabolites and HPCs, we assessed and compared hydroxylated (OH) PCBs and OH-PBDEs relative to PCBs and PBDEs, respectively, in the plasma of adult male common snapping turtles (Chelydra serpentina). Blood samples were collected from 62 snapping turtles (2001-2004) at 12 wetland sites between the Detroit River and the St. Lawrence River on the Canadian side of the Laurentian Great Lakes of North America. Turtles were sampled from sites designated as Areas of Concern (AOCs) and from a relatively clean reference site in southern Georgian Bay (Tiny Marsh), Lake Huron. Plasma concentrations of Σ46PCB (10-340 ng/g wet weight (ww)) and Σ28OH-PCB (3-83 ng/g ww) were significantly greater (pturtles from the Turkey Creek and Muddy Creek-Wheatley Harbour sites in Lake Erie compared with the reference site turtles. The HPC, pentachlorophenol (PCP), had a mean concentration of 9.6±1.1 ng/g ww. Of the 28 OH-CB congeners screened for, 4-OH-CB187 (42±7 ng/g ww) was the most concentrated of all HPCs measured. Of the 14 OH-BDE congeners examined, four (4'-OH-BDE17, 3-OH-BDE47, 5-OH-BDE47 and 4'-OH-BDE49) were consistently found in all plasma samples. p,p'-DDE was the most concentrated of the 18 organochlorine pesticides (OCPs) examined. The mean concentrations of circulating total thyroxine (TT4), dehydroretinol and retinol in the plasma of the male snapping turtles regardless of sampling site were 5.4±0.3, 81±4.7 and 291±13 ng

  1. The Marine Metabolite SZ-685C Induces Apoptosis in Primary Human Nonfunctioning Pituitary Adenoma Cells by Inhibition of the Akt Pathway in Vitro

    Directory of Open Access Journals (Sweden)

    Xin Wang

    2015-03-01

    Full Text Available Nonfunctioning pituitary adenoma (NFPA is one of the most common types of pituitary adenoma. The marine anthraquinone derivative SZ-685C has been isolated from the secondary metabolites of the mangrove endophytic fungus Halorosellinia sp. (No. 1403 which is found in the South China Sea. Recent research has shown that SZ-685C possesses anticancer and tumor suppressive effects. The tetrazolium-based colorimetric assay (MTT assay to investigate the different effect of the marine compound SZ-685C on the proliferation of primary human NFPA cells, rat normal pituitary cells (RPCs and rat prolactinoma MMQ cell lines. Hoechst 33342 dye/propidium iodide (PI double staining and fluorescein isothiocyanate-conjugated Annexin V/PI (Annexin V-FITC/PI apoptosis assays detected an enhanced rate of apoptosis in cells treated with SZ-685C. Enhanced expression levels of caspase 3 and phosphate and tensin homolog (PTEN were determined by Western blotting. Notably, the protein expression levels of Akt were decreased when the primary human NFPA cells were treated with SZ-685C. Here, we show that SZ-685C induces apoptosis of human NFPA cells through inhibition of the Akt pathway in vitro. The understanding of apoptosis has provided the basis for novel targeted therapies that can induce death in cancer cells or sensitize them to established cytotoxic agents and radiation therapy.

  2. Abscisic Acid Induced Changes in Production of Primary and Secondary Metabolites, Photosynthetic Capacity, Antioxidant Capability, Antioxidant Enzymes and Lipoxygenase Inhibitory Activity of Orthosiphon stamineus Benth.

    Directory of Open Access Journals (Sweden)

    Mohd Hafiz Ibrahim

    2013-07-01

    Full Text Available An experiment was conducted to investigate and distinguish the relationships in the production of total phenolics, total flavonoids, soluble sugars, H2O2, O2−, phenylalanine ammonia lyase (PAL activity, leaf gas exchange, antioxidant activity, antioxidant enzyme activity [ascorbate peroxidase (APX, catalase (CAT, superoxide dismutase (SOD and Lipoxygenase inhibitory activity (LOX] under four levels of foliar abscisic acid (ABA application (0, 2, 4, 6 µM for 15 weeks in Orthosiphon stamineus Benth. It was found that the production of plant secondary metabolites, soluble sugars, antioxidant activity, PAL activity and LOX inhibitory activity was influenced by foliar application of ABA. As the concentration of ABA was increased from 0 to 6 µM the production of total phenolics, flavonoids, sucrose, H2O2, O2−, PAL activity and LOX inhibitory activity was enhanced. It was also observed that the antioxidant capabilities (DPPH and ORAC were increased. This was followed by increases in production of antioxidant enzymes APX, CAT and SOD. Under high application rates of ABA the net photosynthesis and stomatal conductance was found to be reduced. The production of primary and secondary metabolites displayed a significant positive relationship with H2O2 (total phenolics, r2 = 0.877; total flavonoids, r2 = 0.812; p ≤ 0.05 and O2− (total phenolics, r2 = 0.778; total flavonoids, r2 = 0.912; p ≤ 0.05. This indicated that increased oxidative stress at high application rates of ABA, improved the production of phytochemicals.

  3. Does the Presence of Primary Circulating Prostate Cells Imply the Presence of Agressive Prostate Cancer with Early Biochemical Failure: a Comparison with the Walz Nomogram.

    Science.gov (United States)

    Murray, Nigel P; Reyes, Eduardo; Orellana, Nelson; Fuentealba, Cynthia; Orellana, Sebastian; Jacob, Omar

    2016-01-01

    To determine the utility of primary circulating prostate cells (CPC) for predicting early biochemical failure after radical prostatectomy for prostate cancer and compare the results with the Walz nomogram. A single centre prospective study of men with prostate cancer treated with radical prostatectomy was conducted between 2004 and 2014. Clinicalpathological details were registered, along with total serum PSA presurgery, Gleason score, extracapsular extension, positive surgical margins, infiltration of lymph nodes, seminal vesicles and pathological stage. Primary circulating prostate cells were obtained using differential gel centrifugation and detected using standard immunocytochemistry with antiPSA. Biochemical failure was defined as a PSA >0.2ng/ml, predictive values were calculated using the Walz nomagram and CPC detection. A total of 285 men participated, of whom 103/285 (36.1%) suffered biochemcial failure; 32/103 (31.1%) within two years of radical prostatectomy. Men with higher Gleason scores, higher pathological stage, infiltration of the surgical margin or prostate capsule and infiltration of seminal vesicles were more likely to undergo biochemical failure. There was a significant increase in the frequency of biochemical failure with increasing number of CPCs detected (p<0.0004 Chi squared for trend) and increasing percent prediction for the Walz nomogram (p<0.0001 Chi squared for trends). The positive predictive value of primary CPC detection, even using a cutoff point of ≥ 4 cells/sample was very low. The detection of primary CPCs in men as a prognostic factor pretreatment fails to identify those at high risk of biochemical failure within two years of curative therapy. This is in keeping with their biological significance, that the majority of them will be eliminated by the primary therapy and thus have no influence on the subsequent clinical history of the patient.

  4. Characterization of main primary and secondary metabolites and in vitro antioxidant and antihyperglycemic properties in the mesocarp of three biotypes of Pouteria lucuma.

    Science.gov (United States)

    Fuentealba, Claudia; Gálvez, Lena; Cobos, Ariel; Olaeta, José Antonio; Defilippi, Bruno G; Chirinos, Rosana; Campos, David; Pedreschi, Romina

    2016-01-01

    Pouteria lucuma is an Andean fruit from pre-Incas' times highly appreciated due to its characteristic flavor and taste in its homeland. We characterized the primary (e.g., sugars and organic acids), and secondary (e.g., phenolics and carotenoids) and in vitro antioxidant and antihyperglycemic properties of Rosalia, Montero and Leiva 1 lucuma biotypes. Significant differences were found in these metabolites and functional properties related to biotype and ripeness stage. Results showed significant amounts of sugars (119.4-344 mg total sugars g(-1)DW) and organic acids (44.4-30.0 mg g(-1)DW) and functional associated compounds such as ascorbic acid (0.35-1.07 mg g(-1)DW), total phenolics (0.7-61.6 mg GAE g(-1)DW) and total carotenoids (0.22-0.50 mg β-carotene g(-1)DW). Important in vitro antioxidant and antihyperglycemic properties were found and provide the base for the standardization of lucuma harvest and postharvest focused not only on the enhancement of sensory but functional properties. Copyright © 2015 Elsevier Ltd. All rights reserved.

  5. Sequential metabolism of secondary alkyl amines to metabolic-intermediate complexes: opposing roles for the secondary hydroxylamine and primary amine metabolites of desipramine, (s)-fluoxetine, and N-desmethyldiltiazem.

    Science.gov (United States)

    Hanson, Kelsey L; VandenBrink, Brooke M; Babu, Kantipudi N; Allen, Kyle E; Nelson, Wendel L; Kunze, Kent L

    2010-06-01

    Three secondary amines desipramine (DES), (S)-fluoxetine [(S)-FLX], and N-desmethyldiltiazem (MA) undergo N-hydroxylation to the corresponding secondary hydroxylamines [N-hydroxydesipramine, (S)-N-hydroxyfluoxetine, and N-hydroxy-N-desmethyldiltiazem] by cytochromes P450 2C11, 2C19, and 3A4, respectively. The expected primary amine products, N-desmethyldesipramine, (S)-norfluoxetine, and N,N-didesmethyldiltiazem, are also observed. The formation of metabolic-intermediate (MI) complexes from these substrates and metabolites was examined. In each example, the initial rates of MI complex accumulation followed the order secondary hydroxylamine > secondary amine > primary amine, suggesting that the primary amine metabolites do not contribute to formation of MI complexes from these secondary amines. Furthermore, the primary amine metabolites, which accumulate in incubations of the secondary amines, inhibit MI complex formation. Mass balance studies provided estimates of the product ratios of N-dealkylation to N-hydroxylation. The ratios were 2.9 (DES-CYP2C11), 3.6 [(S)-FLX-CYP2C19], and 0.8 (MA-CYP3A4), indicating that secondary hydroxylamines are significant metabolites of the P450-mediated metabolism of secondary alkyl amines. Parallel studies with N-methyl-d(3)-desipramine and CYP2C11 demonstrated significant isotopically sensitive switching from N-demethylation to N-hydroxylation. These findings demonstrate that the major pathway to MI complex formation from these secondary amines arises from N-hydroxylation rather than N-dealkylation and that the primary amines are significant competitive inhibitors of MI complex formation.

  6. Per-rectal portal scintigraphy for the evaluation of portal circulation in patients with primary biliary cirrhosis

    Energy Technology Data Exchange (ETDEWEB)

    Shiomi, Susumu; Seki, Shuichi; Harihara, Shigeyoshi; Kuroki, Tetsuo; Kobayashi, Kenzo; Kurai, Osamu; Ikeoka, Naoko; Monna, Takeyuki; Yamamoto, Sukeo

    1988-10-01

    Portal circulation in patients with chronic liver diseases was evaluated by a new method named per-rectal portal scintigraphy. Following instillation of a solution containing 10 mCi of /sup 99m/TcO/sub 4//sup -/ into the upper part of the rectum, serial scintigrams were taken sequentially. At the same time, the radioactivity curves over the liver and the heart were recorded sequentially. Per-rectal portal shunt indices were calculated from serial radioactivities on the liver and the heart. 1) Per-rectal portal shunt indices (SI) were ranged from 1.9 % to 5.2 % (mean 4.1 %) in the healthy subjects. In patients with hepatitis the mean SI was 6.9 %, in patients with cirrhosis it was 52.9 %, in patients with PBC it was 46.8 % and in patients with IPH it was 54.4 %. 2) The SI was higher in cirrhotic patients with esophageal varices than in those without (p < 0.001). The SI was higher in cirrhotic patients with encephalopathy than in those without (p < 0.01). 3) A good correlation (r = 0.774) was obtained between SI and ICGR-15. But in the patients with PBC and IPH, ICGR-15 was lower than that of the patients with chronic liver diseases who show same SI as the patients with PBC and IPH. A good correlation (r = -0.716) was obtained between SI and cholinesterase. But in the patients with PBC and IPH, cholinesterase was lower than that of the patients with chronic liver diseases who show same SI as the patients with PBC and IPH.

  7. Circulating CXCR5+CD4+ T cells assist in the survival and growth of primary diffuse large B cell lymphoma cells through interleukin 10 pathway

    International Nuclear Information System (INIS)

    Cha, Zhanshan; Qian, Guangfang; Zang, Yan; Gu, Haihui; Huang, Yanyan; Zhu, Lishuang; Li, Jinqi; Liu, Yang; Tu, Xiaohua; Song, Haihan; Qian, Baohua

    2017-01-01

    Diffuse large B cell lymphoma (DLBCL) is a common and aggressive cancer caused by the malignant transformation of B cells. Although it has been established that the follicular helper T (Tfh) cells play a central role in B cell development, little information is available on their involvement in DLBCL pathogenesis. We studied the role of the peripheral Tfh equivalent, the CXCR5"+ CD4"+ T cells, in DLBCL. Data showed that compared to CXCR5"- CD4"+ T cells, CXCR5"+ CD4"+ T cells were significantly more effective at promoting the proliferation as well as inhibiting the apoptosis of primary autologous DLBCL tumor cells. Surprisingly, we found that at equal cell numbers, CXCR5"+ CD4"+ T cells in DLBCL patients secreted significantly less interleukin (IL)-21 than CXCR5"- CD4"+ T cells, while the level of IL-10 secretion was significant elevated in the CXCR5"+ compartment compared to the CXCR5"- compartment. Neutralization of IL-10 in the primary DLBCL-CXCR5"+ CD4"+ T cell coculture compromised the CXCR5"+ CD4"+ T cell-mediated pro-tumor effects, in a manner that was dependent on the concentration of anti-IL-10 antibodies. The CXCR5"+ compartment also contained significantly lower frequencies of cytotoxic CD4"+ T cells than the CXCR5"- compartment. In conclusion, our investigations discovered a previously unknown pro-tumor role of CXCR5-expressing circulating CD4"+ T cells, which assisted the survival and proliferation of primary DLBCL cells through IL-10. - Highlights: • We studied the role of the peripheral Tfh in DLBCL. • Tfh were effective at promoting the proliferation of primary DLBCL tumor cells. • Tfh were effective at inhibiting the apoptosis of primary DLBCL tumor cells. • IL-10 secretion in Tfh was significant elevated in DLBCL. • Neutralization of IL-10 compromised Tfh-mediated pro-tumor effects.

  8. Altered expression of circulating microRNA in plasma of patients with primary osteoarthritis and in silico analysis of their pathways.

    Directory of Open Access Journals (Sweden)

    Verónica M Borgonio Cuadra

    Full Text Available OBJECTIVE: To analyze a set of circulating microRNA (miRNA in plasma from patients with primary Osteoarthritis (OA and describe the biological significance of altered miRNA in OA based on an in silico analysis of their target genes. METHODS: miRNA expression was analyzed using TaqMan Low Density Arrays and independent assays. The search for potential messenger RNA (mRNA targets of the differentially expressed miRNA was performed by means of the miRWalk and miRecords database; we conducted the biological relevance of the predicted miRNA targets by pathway analysis with the Reactome and DAVID databases. RESULTS: We measured the expression of 380 miRNA in OA; 12 miRNA were overexpressed under the OA condition (p value, ≤0.05; fold change, >2. These results were validated by the detection of some selected miRNA by quantitative PCR (qPCR. In silico analysis showed that target messenger RNA (mRNA were potentially regulated by these miRNA, including genes such as SMAD1, IL-1B, COL3A, VEGFA, and FGFR1, important in chondrocyte maintenance and differentiation. Some metabolic pathways affected by the miRNA: mRNA ratio are signaling Bone morphogenetic proteins (BMP, Platelet-derived growth factor (PDGF, and Nerve growth factor (NGF, these latter two involved in the process of pain. CONCLUSIONS: We identified 12 miRNA in the plasma of patients with primary OA. Specific miRNA that are altered in the disease could be released into plasma, either due to cartilage damage or to an inherent cellular mechanism. Several miRNA could regulate genes and pathways related with development of the disease; eight of these circulating miRNA are described, to our knowledge, for first time in OA.

  9. Simultaneous determination of clevidipine and its primary metabolite in dog plasma by liquid chromatography-tandem mass spectrometry: Application to pharmacokinetic study.

    Science.gov (United States)

    Zhou, Ying; Li, Huqun; He, Xiaomeng; Jia, Mengmeng; Ni, Yang; Xu, Mingzhen; Chen, Hui; Li, Weiyong

    2014-11-01

    A simple and rapid liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated for the simultaneous determination of clevidipine and its primary metabolite H152/81 in dog plasma after protein precipitation with acetonitrile using felodipine as the internal standard (IS). Chromatographic separation was performed on a XB C18 column (2.1mm×50mm, 3.5μm) under isocratic conditions with the mobile phase consisting of acetonitrile and 20mM ammonium acetate buffer (pH 7.0) (40:60, v/v) at the flow rate of 0.3ml/min. The run time was 5.5min. Mass spectrometric analysis was performed on a triple quadrupole mass spectrometer operated in the multiple reaction monitoring (MRM) mode with the transitions of m/z 473.0→338.2 for clevidipine, m/z 356.1→324.0 for H152/81 and m/z 383.9→338.2 for the IS. The method was fully validated in terms of selectivity, linearity, lower limit of quantification (LLOQ), accuracy, precision, stability, matrix effect and recovery over a concentration range of 0.15-200ng/ml for clevidipine and 10-2000ng/ml for H152/81, respectively. The analytical method was applied to support a pharmacokinetic study of simultaneous determination of clevidipine and H152/81 in ten healthy beagle dogs. Copyright © 2014 Elsevier B.V. All rights reserved.

  10. In vivo proton magnetic resonance spectroscopy (1H-MRS) evaluation of the metabolite concentration of optic radiation in primary open angle glaucoma

    Energy Technology Data Exchange (ETDEWEB)

    Sidek, Sabrilhakim [University of Malaya, Department of Biomedical Imaging, University Malaya Research Imaging Centre (UMRIC), Kuala Lumpur (Malaysia); Universiti Teknologi MARA, Medical Imaging Unit, Faculty of Medicine, Sg Buloh, Selangor (Malaysia); Ramli, Norlisah; Rahmat, Kartini; Kuo, Tan Li [University of Malaya, Department of Biomedical Imaging, University Malaya Research Imaging Centre (UMRIC), Kuala Lumpur (Malaysia); Ramli, Norlina Mohd; Abdulrahman, Fadzlina [University of Malaya, Department of Ophthalmology, Faculty of Medicine, Kuala Lumpur (Malaysia)

    2016-12-15

    To compare the metabolite concentration of optic radiation in glaucoma patients with that of healthy subjects using Proton Magnetic Resonance Spectroscopy (1H-MRS). 1H-MRS utilising the Single-Voxel Spectroscopy (SVS) technique was performed using a 3.0Tesla MRI on 45 optic radiations (15 from healthy subjects, 15 from mild glaucoma patients, and 15 from severe glaucoma patients). A standardised Volume of Interest (VOI) of 20 x 20 x 20 mm was placed in the region of optic radiation. Mild and severe glaucoma patients were categorised based on the Hodapp-Parrish-Anderson (HPA) classification. Mean and multiple group comparisons for metabolite concentration and metabolite concentration ratio between glaucoma grades and healthy subjects were obtained using one-way ANOVA. The metabolite concentration and metabolite concentration ratio between the optic radiations of glaucoma patients and healthy subjects did not demonstrate any significant difference (p > 0.05). Our findings show no significant alteration of metabolite concentration associated with neurodegeneration that could be measured by single-voxel 1H-MRS in optic radiation among glaucoma patients. (orig.)

  11. Posaconazole (Noxafil, SCH 56592), a new azole antifungal drug, was a discovery based on the isolation and mass spectral characterization of a circulating metabolite of an earlier lead (SCH 51048).

    Science.gov (United States)

    Nomeir, Amin A; Pramanik, Birendra N; Heimark, Larry; Bennett, Frank; Veals, John; Bartner, Peter; Hilbert, Maryjane; Saksena, Anil; McNamara, Paul; Girijavallabhan, Viyyoor; Ganguly, Ashit K; Lovey, Raymond; Pike, Russell; Wang, Haiyan; Liu, Yi-Tsung; Kumari, Pramila; Korfmacher, Walter; Lin, Chin-Chung; Cacciapuoti, Anthony; Loebenberg, David; Hare, Roberta; Miller, George; Pickett, Cecil

    2008-04-01

    Posaconazole (SCH 56592) is a novel triazole antifungal drug that is marketed in Europe and the United States under the trade name 'Noxafil' for prophylaxis against invasive fungal infections. SCH 56592 was discovered as a possible active metabolite of SCH 51048, an earlier lead. Initial studies have shown that serum concentrations determined by a microbiological assay were higher than those determined by HPLC from animals dosed with SCH 51048. Subsequently, several animals species were dosed with (3)H-SCH 51048 and the serum was analyzed for total radioactivity, SCH 51048 concentration and antifungal activity. The antifungal activity was higher than that expected based on SCH 51048 serum concentrations, confirming the presence of active metabolite(s). Metabolite profiling of serum samples at selected time intervals pinpointed the peak that was suspected to be the active metabolite. Consequently, (3)H-SCH 51048 was administered to a large group of mice, the serum was harvested and the metabolite was isolated by extraction and semipreparative HPLC. LC-MS/MS analysis suggested that the active metabolite is a secondary alcohol with the hydroxyl group in the aliphatic side chain of SCH 51048. All corresponding monohydroxylated diastereomeric mixtures were synthesized and characterized. The HPLC retention time and LC-MS/MS spectra of the diastereomeric secondary alcohols of SCH 51048 were similar to those of the isolated active metabolite. Finally, all corresponding individual monohydroxylated diasteriomers were synthesized and evaluated for in vitro and in vivo antifungal potencies, as well as pharmacokinetics. SCH 56592 emerged as the candidate with the best overall profile.

  12. The efficacy of lapatinib in metastatic breast cancer with HER2 non-amplified primary tumors and EGFR positive circulating tumor cells: a proof-of-concept study.

    Directory of Open Access Journals (Sweden)

    Justin Stebbing

    Full Text Available Analysis of circulating tumor cells (CTCs provides real-time measures of cancer sub-populations with potential for CTC-directed therapeutics. We examined whether lapatinib which binds both HER2 and EGFR could induce depletion of the EGFR-positive pool of CTCs, which may in turn lead to clinical benefits.Patients with metastatic breast cancer and HER2 non-amplified primary tumors with EGFR-positive CTCs were recruited and lapatinib 1500 mg daily was administered, in a standard two step phase 2 trial.There were no responses leading to termination at the first analysis with 16 patients recruited out of 43 screened. In 6 out of 14 (43% individuals eligible for the efficacy analysis, a decrease in CTCs was observed with most of these having a greater decrease in their EGFR-positive CTC pool.This is one of the first studies of CTC-directed therapeutics and suggests that lapatinib monotherapy is not having any demonstrable clinical effects by reducing the EGFR-positive pool of CTCs in HER2 non-amplified primary tumors. Our attempt to expand the pool of patients eligible for a targeted therapy was unsuccessful; the role of clonal populations in cancer biology and therapeutic strategies to control them will require extensive evaluation in years to come.Clinical trials.gov NCT00820924.

  13. Morphine metabolites

    DEFF Research Database (Denmark)

    Christrup, Lona Louring

    1997-01-01

    , morphine-3-glucuronide (M3G) and morphine-6-glucuronide (M6G) are the major metabolites of morphine. The metabolism of morphine occurs not only in the liver, but may also take place in the brain and the kidneys. The glucuronides are mainly eliminated via bile and urine. Glucuronides as a rule...... are considered as highly polar metabolites unable to cross the blood-brain barrier. Although morphine glucuronidation has been demonstrated in human brain tissue, the capacity is very low compared to that of the liver, indicating that the M3G and M6G concentrations observed in the cerebrospinal fluid (CSF) after...... systemic administration reflect hepatic metabolism of morphine and that the morphine glucuronides, despite their high polarity, can penetrate into the brain. Like morphine, M6G has been shown to be relatively more selective for mu-receptors than for delta- and kappa-receptors while M3G does not appear...

  14. Urinary estrogen metabolites and breast cancer

    DEFF Research Database (Denmark)

    Dallal, Cher M; Stone, Roslyn A; Cauley, Jane A

    2013-01-01

    Background: Circulating estrogens are associated with increased breast cancer risk, yet the role of estrogen metabolites in breast carcinogenesis remains unclear. This combined analysis of 5 published studies evaluates urinary 2-hydroxyestrone (2-OHE1), 16a-hydroxyestrone (16a-OHE1......), and their ratio (2:16a-OHE1) in relation to breast cancer risk. ¿Methods: Primary data on 726 premenopausal women (183 invasive breast cancer cases and 543 controls) and 1,108 postmenopausal women (385 invasive breast cancer cases and 723 controls) were analyzed. Urinary estrogen metabolites were measured using...... premenopausal 2:16a-OHE1 was suggestive of reduced breast cancer risk overall (study-adjusted ORIIIvsI=0.80; 95% CI: 0.49-1.32) and for estrogen receptor negative (ER-) subtype (ORIIIvsI=0.33; 95% CI: 0.13-0.84). Among postmenopausal women, 2:16a-OHE1 was unrelated to breast cancer risk (study-adjusted ORIIIvs...

  15. Circulating CXCR5+CD4+ T cells assist in the survival and growth of primary diffuse large B cell lymphoma cells through interleukin 10 pathway

    Energy Technology Data Exchange (ETDEWEB)

    Cha, Zhanshan [Department of Transfusion, Changhai Hospital, Second Military Medical University, Shanghai 200433 (China); Qian, Guangfang [Department of Endocrinology, Zhangqiu Municipal Hospital of Traditional Chinese Medicine, Zhangqiu, Shandong 250200 (China); Zang, Yan; Gu, Haihui; Huang, Yanyan; Zhu, Lishuang; Li, Jinqi; Liu, Yang; Tu, Xiaohua [Department of Transfusion, Changhai Hospital, Second Military Medical University, Shanghai 200433 (China); Song, Haihan [Emergency Center, East Hospital, Shanghai 200120 (China); Qian, Baohua, E-mail: qianbhl963@163.com [Department of Transfusion, Changhai Hospital, Second Military Medical University, Shanghai 200433 (China)

    2017-01-01

    Diffuse large B cell lymphoma (DLBCL) is a common and aggressive cancer caused by the malignant transformation of B cells. Although it has been established that the follicular helper T (Tfh) cells play a central role in B cell development, little information is available on their involvement in DLBCL pathogenesis. We studied the role of the peripheral Tfh equivalent, the CXCR5{sup +} CD4{sup +} T cells, in DLBCL. Data showed that compared to CXCR5{sup -} CD4{sup +} T cells, CXCR5{sup +} CD4{sup +} T cells were significantly more effective at promoting the proliferation as well as inhibiting the apoptosis of primary autologous DLBCL tumor cells. Surprisingly, we found that at equal cell numbers, CXCR5{sup +} CD4{sup +} T cells in DLBCL patients secreted significantly less interleukin (IL)-21 than CXCR5{sup -} CD4{sup +} T cells, while the level of IL-10 secretion was significant elevated in the CXCR5{sup +} compartment compared to the CXCR5{sup -} compartment. Neutralization of IL-10 in the primary DLBCL-CXCR5{sup +} CD4{sup +} T cell coculture compromised the CXCR5{sup +} CD4{sup +} T cell-mediated pro-tumor effects, in a manner that was dependent on the concentration of anti-IL-10 antibodies. The CXCR5{sup +} compartment also contained significantly lower frequencies of cytotoxic CD4{sup +} T cells than the CXCR5{sup -} compartment. In conclusion, our investigations discovered a previously unknown pro-tumor role of CXCR5-expressing circulating CD4{sup +} T cells, which assisted the survival and proliferation of primary DLBCL cells through IL-10. - Highlights: • We studied the role of the peripheral Tfh in DLBCL. • Tfh were effective at promoting the proliferation of primary DLBCL tumor cells. • Tfh were effective at inhibiting the apoptosis of primary DLBCL tumor cells. • IL-10 secretion in Tfh was significant elevated in DLBCL. • Neutralization of IL-10 compromised Tfh-mediated pro-tumor effects.

  16. Niacin and its metabolites as master regulators of macrophage activation.

    Science.gov (United States)

    Montserrat-de la Paz, Sergio; Naranjo, M Carmen; Lopez, Sergio; Abia, Rocio; Muriana, Francisco J Garcia; Bermudez, Beatriz

    2017-01-01

    Niacin is a broad-spectrum lipid-regulating drug used for clinical therapy of chronic high-grade inflammatory diseases. However, the mechanisms by which either niacin or the byproducts of its catabolism ameliorate these inflammatory diseases are not clear yet. Human circulating monocytes and mature macrophages were used to analyze the effects of niacin and its metabolites (NAM, NUA and 2-Pyr) on oxidative stress, plasticity and inflammatory response by using biochemical, flow cytometry, quantitative real-time PCR and Western blot technologies. Niacin, NAM and 2-Pyr significantly decreased ROS, NO and NOS2 expression in LPS-treated human mature macrophages. Niacin and NAM skewed macrophage polarization toward antiinflammatory M2 macrophage whereas a trend toward proinflammatory M1 macrophage was noted following treatment with NUA. Niacin and NAM also reduced the inflammatory competence of LPS-treated human mature macrophages and promoted bias toward antiinflammatory CD14 + CD16 ++ nonclassical human primary monocytes. This study reveals for the first time that niacin and its metabolites possess antioxidant, reprogramming and antiinflammatory properties on human primary monocytes and monocyte-derived macrophages. Our findings imply a new understanding of the mechanisms by which niacin and its metabolites favor a continuous and gradual plasticity process in the human monocyte/macrophage system. Copyright © 2016 Elsevier Inc. All rights reserved.

  17. Biotransformation of primary nicotine metabolites. I. In vivo metabolism of R-(+)-[14C-NCH3]N-methylnicotinium ion in the guinea pig

    International Nuclear Information System (INIS)

    Pool, W.F.; Crooks, P.A.

    1985-01-01

    The in vivo biotransformation and tissue distribution of the methylated nicotine metabolite R-(+)-[ 14 C-NCH 3 ]N-methylnicotinium acetate was studied in the guinea pig. The detection and quantification of 24-hr urinary metabolites after ip injection was determined by cation-exchange HPLC interfaced to a radiochemical flowthrough detector. The urinary metabolite profile consisted of five peaks. One eluted close to the void, and three coeluted with authentic standards of N-methylcotininium ion, N-methylnornicotinium ion, and N-methylnicotinium ion. A fifth, and as yet unidentified, metabolite was also detected. Tissue distribution of 14 C label after 24 hr was highest in the adrenal gland and epididymis followed by the gallbladder, bladder, kidney, spleen, and heart. No significant amounts of 14 C were found in the brain. The results indicate that N-methylcotininium ion and N-methylnornicotinium ion are both formed subsequent to the formation of N-methylnicotinium ion in the metabolism of R-(+)-nicotine in the guinea pig

  18. Rationalization and prediction of in vivo metabolite exposures: The role of metabolite kinetics, clearance predictions and in vitro parameters

    Science.gov (United States)

    Lutz, Justin D.; Fujioka, Yasushi; Isoherranen, Nina

    2010-01-01

    Importance of the field Due to growing concerns over toxic or active metabolites, significant efforts have been focused on qualitative identification of potential in vivo metabolites from in vitro data. However, limited tools are available to quantitatively predict their human exposures. Areas covered in this review Theory of clearance predictions and metabolite kinetics is reviewed together with supporting experimental data. In vitro and in vivo data of known circulating metabolites and their parent drugs was collected and the predictions of in vivo exposures of the metabolites were evaluated. What the reader will gain The theory and data reviewed will be useful in early identification of human metabolites that will circulate at significant levels in vivo and help in designing in vivo studies that focus on characterization of metabolites. It will also assist in rationalization of metabolite-to-parent ratios used as markers of specific enzyme activity. Take home message The relative importance of a metabolite in comparison to the parent compound as well as other metabolites in vivo can only be predicted using the metabolites in vitro formation and elimination clearances, and the in vivo disposition of a metabolite can only be rationalized when the elimination pathways of that metabolite are known. PMID:20557268

  19. Evaluation of various solvent systems for lipid extraction from wet microalgal biomass and its effects on primary metabolites of lipid-extracted biomass.

    Science.gov (United States)

    Ansari, Faiz Ahmad; Gupta, Sanjay Kumar; Shriwastav, Amritanshu; Guldhe, Abhishek; Rawat, Ismail; Bux, Faizal

    2017-06-01

    Microalgae have tremendous potential to grow rapidly, synthesize, and accumulate lipids, proteins, and carbohydrates. The effects of solvent extraction of lipids on other metabolites such as proteins and carbohydrates in lipid-extracted algal (LEA) biomass are crucial aspects of algal biorefinery approach. An effective and economically feasible algae-based oil industry will depend on the selection of suitable solvent/s for lipid extraction, which has minimal effect on metabolites in lipid-extracted algae. In current study, six solvent systems were employed to extract lipids from dry and wet biomass of Scenedesmus obliquus. To explore the biorefinery concept, dichloromethane/methanol (2:1 v/v) was a suitable solvent for dry biomass; it gave 18.75% lipids (dry cell weight) in whole algal biomass, 32.79% proteins, and 24.73% carbohydrates in LEA biomass. In the case of wet biomass, in order to exploit all three metabolites, isopropanol/hexane (2:1 v/v) is an appropriate solvent system which gave 7.8% lipids (dry cell weight) in whole algal biomass, 20.97% proteins, and 22.87% carbohydrates in LEA biomass. Graphical abstract: Lipid extraction from wet microalgal biomass and biorefianry approach.

  20. Role of Circulating Fibroblast Growth Factor 21 Measurement in Primary Prevention of Coronary Heart Disease Among Chinese Patients With Type 2 Diabetes Mellitus.

    Science.gov (United States)

    Lee, Chi Ho; Woo, Yu Cho; Chow, Wing Sun; Cheung, Chloe Yu Yan; Fong, Carol Ho Yi; Yuen, Michele Mae Ann; Xu, Aimin; Tse, Hung Fat; Lam, Karen Siu Ling

    2017-06-06

    Fibroblast growth factor 21 (FGF21) has demonstrated beneficial effects on lipid and carbohydrate metabolism. In cross-sectional studies, an association of raised circulating FGF21 levels with coronary heart disease (CHD) was found in some but not all studies. Here we investigated prospectively whether baseline serum FGF21 levels could predict incident CHD in subjects with type 2 diabetes mellitus and no known cardiovascular diseases. Baseline serum FGF21 levels were measured in 3528 Chinese subjects with type 2 diabetes mellitus recruited from the Hong Kong West Diabetes Registry. The role of baseline serum FGF21 levels in predicting incident CHD over a median follow-up of 3.8 years was analyzed using Cox regression analysis. Among 3528 recruited subjects without known cardiovascular diseases, 147 (4.2%) developed CHD over a mean follow-up of 4 years. Baseline serum log-transformed FGF21 levels were significantly higher in those who had incident CHD than those who did not (222.7 pg/mL [92.8-438.4] versus 151.1 pg/mL [75.6-274.6]; P 1). On multivariable Cox regression analysis, baseline serum FGF21 levels, using an optimal cutoff of 206.22 pg/mL derived from our study, independently predicted incident CHD (hazard ratio, 1.55; 95% CI, 1.10-2.19; P =0.013) and significantly improved net reclassification index and integrated discrimination improvement after adjustment for conventional cardiovascular risk factors. We have demonstrated, for the first time, that serum FGF21 level is an independent predictor of incident CHD and might be usefully utilized as a biomarker for identifying type 2 diabetes mellitus subjects with raised CHD risk, for primary prevention. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

  1. Process Control Logic Modification to Mitigate Transient Following Tripping of a Primary Circulating Pump for a 540 MWe PHWR Power Plant

    International Nuclear Information System (INIS)

    Contractor, Ankur D; Gaikwad, Avinash J.; Kumar, Rajesh; Chakraborty, G.; Vhora, S.F.

    2006-01-01

    The 540 MWe Indian Pressurised Heavy Water Reactor (PHWR) incorporates many new features as compared to the earlier 220 MWe PHWRs. To evaluate the new design features like Primary Heat Transport (PHT) system configuration with two loops, four Primary Circulating Pumps (PCPs) and four passes through core, addition of a Pressurizer (surge Tank) in the PHT system along with Feed/Bleed system and their safety related implications, simulation model have been developed. A reactor step-back is proposed following one PCP trip. The corresponding PCP in the healthy loop is tripped to avoid asymmetrical flow and pressure distribution in the two identical loops. In spite of such elaborate provisions, the margins from high/low PHT pressure are small following tripping of one PCP. Mathematical models for all the major components and sub-systems of the proposed 540 MWe PHWR were developed based on the conservation equations of mass, momentum, energy and equation of state. All the associated control systems are also modeled. The PHT system includes the reactor core with nuclear fuel, PCP, PHT system pressure controller with feed/bleed system and Pressurizer (Surge Tank). The secondary system includes mainly the Steam Generators (SGs), the SG level and pressure controllers, apart from the various steam cycle components. All these models are integrated together to form the Plant Transient Analysis Computer Code Dyna540. The scenario following one PCP trips leads to different states (high/low pressure in Reactor Outlet Header (ROH)) depending upon the banks in which the PCP trips. The pressurizer is connected to two ROHs on one side of the reactor. The system pressure is controlled based on average of four ROHs pressure. In the case of asymmetrical pump operation, this logic leads to a situation where individual ROH pressure goes very near the low/high PHT system pressure trip set point, even though the controlled average pressure is very close to the set pressure. The PHT high

  2. A sex-specific metabolite identified in a marine invertebrate utilizing phosphorus-31 nuclear magnetic resonance.

    Directory of Open Access Journals (Sweden)

    Robert A Kleps

    Full Text Available Hormone level differences are generally accepted as the primary cause for sexual dimorphism in animal and human development. Levels of low molecular weight metabolites also differ between men and women in circulating amino acids, lipids and carbohydrates and within brain tissue. While investigating the metabolism of blue crab tissues using Phosphorus-31 Nuclear Magnetic Resonance, we discovered that only the male blue crab (Callinectes sapidus contained a phosphorus compound with a chemical shift well separated from the expected phosphate compounds. Spectra obtained from male gills were readily differentiated from female gill spectra. Analysis from six years of data from male and female crabs documented that the sex-specificity of this metabolite was normal for this species. Microscopic analysis of male and female gills found no differences in their gill anatomy or the presence of parasites or bacteria that might produce this phosphorus compound. Analysis of a rare gynandromorph blue crab (laterally, half male and half female proved that this sex-specificity was an intrinsic biochemical process and was not caused by any variations in the diet or habitat of male versus female crabs. The existence of a sex-specific metabolite is a previously unrecognized, but potentially significant biochemical phenomenon. An entire enzyme system has been synthesized and activated only in one sex. Unless blue crabs are a unique species, sex-specific metabolites are likely to be present in other animals. Would the presence or absence of a sex-specific metabolite affect an animal's development, anatomy and biochemistry?

  3. Serotonin syndrome following sibutramine poisoning in a child, with sequential quantification of sibutramine and its primary and secondary amine metabolites in plasma.

    Science.gov (United States)

    Bucaretchi, Fábio; de Capitani, Eduardo Mello; Mello, Sueli Moreira; Lanaro, Rafael; Barros, Roberta F; Fernandes, Luciane C R; da Costa, José Luiz; Hyslop, Stephen

    2009-07-01

    To report a case of serotonin syndrome (SS) after sibutramine overdose in a child. A 4-year-old girl was admitted 25 h after accidentally ingesting approximately 27 pills of sibutramine (15 mg, approximately 23 mg/kg). The child developed clinical features suggestive of SS, including diaphoresis, tachycardia, hypertension, agitation, insomnia, incoordination, hypertonia (lower limbs > upper limbs), and hallucinations. Serum creatine phosphokinase levels reached a peak on day 3 (2,577 U/L, reference value sibutramine and the active metabolites, M1 (mono-desmethyl sibutramine) and M2 (di-desmethyl sibutramine), by liquid chromatography/electrospray ionization tandem mass spectrometry in six sequential samples collected from 25 to 147 h post-ingestion revealed a nonlinear decrease in the log-scale plasma concentrations. Treatment was only supportive and involved prolonged sedation to control the agitation, sleeplessness, and hypertension; no cyproheptadine was used. The patient was discharged on day 6 and follow-up revealed no sequelae. To our knowledge, this is the first report of SS after sibutramine overdose in a child, with sequential monitoring of the plasma levels of the drug and its two active metabolites. The growing consumption of weight reducing pills may increase the risk of unintentional acute toxic exposures in children.

  4. Salicylic acid treatment reduces the rot of postharvest citrus fruit by inducing the accumulation of H2O2, primary metabolites and lipophilic polymethoxylated flavones.

    Science.gov (United States)

    Zhu, Feng; Chen, Jiajing; Xiao, Xue; Zhang, Mingfei; Yun, Ze; Zeng, Yunliu; Xu, Juan; Cheng, Yunjiang; Deng, Xiuxin

    2016-09-15

    To comprehensively analyze the effects of salicylic acid (SA) on the storability of Satsuma mandarin (Citrus unshiu), fruits were treated with 2mM SA. The disease incidence of control/SA-treated fruit at 50d and 120d after treatment was 23.3%/10% and 67.3%/23.3%, respectively, suggesting that SA treatment can significantly reduce the rot rate of postharvest citrus fruit. Fruit quality assays revealed that the treatment can maintain fruit firmness without affecting the inner quality. Furthermore, the contents of H2O2 and some defense-related metabolites, such as ornithine and threonine, in citrus pericarp, were significantly increased by SA treatment. Moreover, it was lipophilic polymethoxylated flavones, rather than flavanone glycosides, that accumulated in SA-treated fruits and these can directly inhibit pathogen development. These results suggest that the effects of SA on postharvest citrus fruit may be attributed to the accumulation of H2O2 and defense-related metabolites. Copyright © 2016. Published by Elsevier Ltd.

  5. Enhancement of anti-inflammatory activity of Aloe vera adventitious root extracts through the alteration of primary and secondary metabolites via salicylic acid elicitation.

    Directory of Open Access Journals (Sweden)

    Yun Sun Lee

    Full Text Available Aloe vera (Asphodeloideae is a medicinal plant in which useful secondary metabolites are plentiful. Among the representative secondary metabolites of Aloe vera are the anthraquinones including aloe emodin and chrysophanol, which are tricyclic aromatic quinones synthesized via a plant-specific type III polyketide biosynthesis pathway. However, it is not yet clear which cellular responses can induce the pathway, leading to production of tricyclic aromatic quinones. In this study, we examined the effect of endogenous elicitors on the type III polyketide biosynthesis pathway and identified the metabolic changes induced in elicitor-treated Aloe vera adventitious roots. Salicylic acid, methyl jasmonate, and ethephon were used to treat Aloe vera adventitious roots cultured on MS liquid media with 0.3 mg/L IBA for 35 days. Aloe emodin and chrysophanol were remarkably increased by the SA treatment, more than 10-11 and 5-13 fold as compared with untreated control, respectively. Ultra-performance liquid chromatography-electrospray ionization mass spectrometry analysis identified a total of 37 SA-induced compounds, including aloe emodin and chrysophanol, and 3 of the compounds were tentatively identified as tricyclic aromatic quinones. Transcript accumulation analysis of polyketide synthase genes and gas chromatography mass spectrometry showed that these secondary metabolic changes resulted from increased expression of octaketide synthase genes and decreases in malonyl-CoA, which is the precursor for the tricyclic aromatic quinone biosynthesis pathway. In addition, anti-inflammatory activity was enhanced in extracts of SA-treated adventitious roots. Our results suggest that SA has an important role in activation of the plant specific-type III polyketide biosynthetic pathway, and therefore that the efficacy of Aloe vera as medicinal agent can be improved through SA treatment.

  6. Enhancement of anti-inflammatory activity of Aloe vera adventitious root extracts through the alteration of primary and secondary metabolites via salicylic acid elicitation.

    Science.gov (United States)

    Lee, Yun Sun; Ju, Hyun Kyoung; Kim, Yeon Jeong; Lim, Tae-Gyu; Uddin, Md Romij; Kim, Yeon Bok; Baek, Jin Hong; Kwon, Sung Won; Lee, Ki Won; Seo, Hak Soo; Park, Sang Un; Yang, Tae-Jin

    2013-01-01

    Aloe vera (Asphodeloideae) is a medicinal plant in which useful secondary metabolites are plentiful. Among the representative secondary metabolites of Aloe vera are the anthraquinones including aloe emodin and chrysophanol, which are tricyclic aromatic quinones synthesized via a plant-specific type III polyketide biosynthesis pathway. However, it is not yet clear which cellular responses can induce the pathway, leading to production of tricyclic aromatic quinones. In this study, we examined the effect of endogenous elicitors on the type III polyketide biosynthesis pathway and identified the metabolic changes induced in elicitor-treated Aloe vera adventitious roots. Salicylic acid, methyl jasmonate, and ethephon were used to treat Aloe vera adventitious roots cultured on MS liquid media with 0.3 mg/L IBA for 35 days. Aloe emodin and chrysophanol were remarkably increased by the SA treatment, more than 10-11 and 5-13 fold as compared with untreated control, respectively. Ultra-performance liquid chromatography-electrospray ionization mass spectrometry analysis identified a total of 37 SA-induced compounds, including aloe emodin and chrysophanol, and 3 of the compounds were tentatively identified as tricyclic aromatic quinones. Transcript accumulation analysis of polyketide synthase genes and gas chromatography mass spectrometry showed that these secondary metabolic changes resulted from increased expression of octaketide synthase genes and decreases in malonyl-CoA, which is the precursor for the tricyclic aromatic quinone biosynthesis pathway. In addition, anti-inflammatory activity was enhanced in extracts of SA-treated adventitious roots. Our results suggest that SA has an important role in activation of the plant specific-type III polyketide biosynthetic pathway, and therefore that the efficacy of Aloe vera as medicinal agent can be improved through SA treatment.

  7. Metabolite ratios as potential biomarkers for type 2 diabetes : a DIRECT study

    NARCIS (Netherlands)

    Molnos, Sophie; Wahl, Simone; Haid, Mark; Eekhoff, E Marelise W; Pool, René; Floegel, Anna; Deelen, Joris; Much, Daniela; Prehn, Cornelia; Breier, Michaela; Draisma, Harmen H; van Leeuwen, Nienke; Simonis-Bik, Annemarie M C; Jonsson, Anna; Willemsen, Gonneke; Bernigau, Wolfgang; Wang-Sattler, Rui; Suhre, Karsten; Peters, Annette; Thorand, Barbara; Herder, Christian; Rathmann, Wolfgang; Roden, Michael; Gieger, Christian; Kramer, Mark H H; van Heemst, Diana; Pedersen, Helle K; Gudmundsdottir, Valborg; Schulze, Matthias B; Pischon, Tobias; de Geus, Eco J C; Boeing, Heiner; Boomsma, Dorret I; Ziegler, Anette G; Slagboom, P. Eline; Hummel, Sandra; Beekman, Marian; Grallert, Harald; Brunak, Søren; McCarthy, Mark I; Gupta, Ramneek; Pearson, Ewan R; Adamski, Jerzy; 't Hart, Leen M

    2018-01-01

    AIMS/HYPOTHESIS: Circulating metabolites have been shown to reflect metabolic changes during the development of type 2 diabetes. In this study we examined the association of metabolite levels and pairwise metabolite ratios with insulin responses after glucose, glucagon-like peptide-1 (GLP-1) and

  8. Metabolite Profiling of Red Sea Corals

    KAUST Repository

    Ortega, Jovhana Alejandra

    2016-12-01

    Looking at the metabolite profile of an organism provides insights into the metabolomic state of a cell and hence also into pathways employed. Little is known about the metabolites produced by corals and their algal symbionts. In particular, corals from the central Red Sea are understudied, but interesting study objects, as they live in one of the warmest and most saline environments and can provide clues as to the adjustment of corals to environmental change. In this study, we applied gas chromatography – mass spectrometry (GC–MS) metabolite profiling to analyze the metabolic profile of four coral species and their associated symbionts: Fungia granulosa, Acropora hemprichii, Porites lutea, and Pocillopora verrucosa. We identified and quantified 102 compounds among primary and secondary metabolites across all samples. F. granulosa and its symbiont showed a total of 59 metabolites which were similar to the 51 displayed by P. verrucosa. P. lutea and A. hemprichii both harbored 40 compounds in conjunction with their respective isolated algae. Comparing across species, 28 metabolites were exclusively present in algae, while 38 were exclusive to corals. A principal component and cluster analyses revealed that metabolite profiles clustered between corals and algae, but each species harbored a distinct catalog of metabolites. The major classes of compounds were carbohydrates and amino acids. Taken together, this study provides a first description of metabolites of Red Sea corals and their associated symbionts. As expected, the metabolites of coral hosts differ from their algal symbionts, but each host and algal species harbor a unique set of metabolites. This corroborates that host-symbiont species pairs display a fine-tuned complementary metabolism that provide insights into the specific nature of the symbiosis. Our analysis also revealed aquatic pollutants, which suggests that metabolite profiling might be used for monitoring pollution levels and assessing

  9. Blood burden of di(2-ethylhexyl) phthalate and its primary metabolite mono(2-ethylhexyl) phthalate in pregnant and nonpregnant rats and marmosets

    International Nuclear Information System (INIS)

    Kessler, Winfried; Numtip, Wanwiwa; Grote, Konstanze; Csanady, Gyoergy A.; Chahoud, Ibrahim; Filser, Johannes G.

    2004-01-01

    A comparison of the dose-dependent blood burden of di(2-ethylhexyl) phthalate (DEHP) and mono(2-ethylhexyl) phthalate (MEHP) in pregnant and nonpregnant rats and marmosets is presented. Sprague-Dawley rats and marmosets were treated orally with 30 or 500 mg DEHP/kg per day, nonpregnant animals on 7 (rats) and 29 (marmosets) consecutive days, pregnant animals on gestation days 14-19 (rats) and 96-124 (marmosets). In addition, rats received a single dose of 1000 mg DEHP/kg. Blood was collected up to 48 h after dosing. Concentrations of DEHP and MEHP in blood were determined by GC/MS. In rats, normalized areas under the concentration-time curves (AUCs) of DEHP were two orders of magnitude smaller than the normalized AUCs of the first metabolite MEHP. Metabolism of MEHP was saturable. Repeated DEHP treatment and pregnancy had only little influence on the normalized AUC of MEHP. In marmosets, most of MEHP concentration-time courses oscillated. Normalized AUCs of DEHP were at least one order of magnitude smaller than those of MEHP. In pregnant marmosets, normalized AUCs of MEHP were similar to those in nonpregnant animals with the exception that at 500 mg DEHP/kg per day, the normalized AUCs determined on gestation days 103, 117, and 124 were distinctly smaller. The maximum concentrations of MEHP in blood of marmosets were up to 7.5 times and the normalized AUCs up to 16 times lower than in rats receiving the same daily oral DEHP dose per kilogram of body weight. From this toxicokinetic comparison, DEHP can be expected to be several times less effective in the offspring of marmosets than in that of rats if the blood burden by MEHP in dams can be regarded as a dose surrogate for the MEHP burden in their fetuses

  10. Circulating Plasma Levels of MicroRNA-21 and MicroRNA-221 Are Potential Diagnostic Markers for Primary Intrahepatic Cholangiocarcinoma

    Science.gov (United States)

    Kemeny, Nancy; Kingham, T. Peter; Allen, Peter J.; D’Angelica, Michael I.; DeMatteo, Ronald P.; Betel, Doron; Klimstra, David; Jarnagin, William R.; Ventura, Andrea

    2016-01-01

    Background MicroRNAs (miRNAs) are potential biomarkers in various malignancies. We aim to characterize miRNA expression in intrahepatic cholangiocarcinoma (ICC) and identify circulating plasma miRNAs with potential diagnostic and prognostic utility. Methods Using deep-sequencing techniques, miRNA expression between tumor samples and non-neoplastic liver parenchyma were compared. Overexpressed miRNAs were measured in plasma from an independent cohort of patients with cholangiocarcinoma using RT-qPCR and compared with that healthy volunteers. The discriminatory ability of the evaluated plasma miRNAs between patients and controls was evaluated with receiving operating characteristic (ROC) curves. Results Small RNAs from 12 ICC and 11 tumor-free liver samples were evaluated. Unsupervised hierarchical clustering using the miRNA expression data showed clear grouping of ICC vs. non-neoplastic liver parenchyma. We identified 134 down-regulated and 128 upregulated miRNAs. Based on overexpression and high fold-change, miR21, miR200b, miR221, and miR34c were measured in plasma from an independent cohort of patients with ICC (n = 25) and healthy controls (n = 7). Significant overexpression of miR-21 and miR-221 was found in plasma from ICC patients. Furthermore, circulating miR-21 demonstrated a high discriminatory ability between patients with ICC and healthy controls (AUC: 0.94). Conclusion Among the differentially expressed miRNAs in ICC, miR-21 and miR-221 are overexpressed and detectable in the circulation. Plasma expression levels of these miRNAs, particularly miR-21, accurately differentiates patients with ICC from healthy controls and could potentially serve as adjuncts in diagnosis. Prospective validation and comparison with other hepatobiliary malignancies is required to establish their potential role as diagnostic and prognostic biomarkers. PMID:27685844

  11. Diurnal variation of connective tissue metabolites in early and long-standing rheumatoid arthritis and in healthy individuals

    DEFF Research Database (Denmark)

    Lottenburger, T; Junker, P; Hørslev-Petersen, K

    2011-01-01

    To study the circadian variability of circulating connective tissue metabolites in patients with very early (VERA) and long-standing rheumatoid arthritis (LRA) and in healthy control individuals.......To study the circadian variability of circulating connective tissue metabolites in patients with very early (VERA) and long-standing rheumatoid arthritis (LRA) and in healthy control individuals....

  12. N-Acetyl-2-Aminofluorene (AAF) Processing in Adult Rat Hepatocytes in Primary Culture Occurs by High-Affinity Low-Velocity and Low-Affinity High-Velocity AAF Metabolite-Forming Systems.

    Science.gov (United States)

    Koch, Katherine S; Moran, Tom; Shier, W Thomas; Leffert, Hyam L

    2018-05-01

    N-acetyl-2-aminofluorene (AAF) is a procarcinogen used widely in physiological investigations of chemical hepatocarcinogenesis. Its metabolic pathways have been described extensively, yet little is known about its biochemical processing, growth cycle expression, and pharmacological properties inside living hepatocytes-the principal cellular targets of this hepatocarcinogen. In this report, primary monolayer adult rat hepatocyte cultures and high specific-activity [ring G-3 H]-N-acetyl-2-aminofluorene were used to extend previous observations of metabolic activation of AAF by highly differentiated, proliferation-competent hepatocytes in long-term cultures. AAF metabolism proceeded by zero-order kinetics. Hepatocytes processed significant amounts of procarcinogen (≈12 μg AAF/106 cells/day). Five ring-hydroxylated and one deacetylated species of AAF were secreted into the culture media. Extracellular metabolite levels varied during the growth cycle (days 0-13), but their rank quantitative order was time invariant: 5-OH-AAF > 7-OH-AAF > 3-OH-AAF > N-OH-AAF > aminofluorene (AF) > 1-OH-AAF. Lineweaver-Burk analyses revealed two principal classes of metabolism: System I (high-affinity and low-velocity), Km[APPARENT] = 1.64 × 10-7  M and VMAX[APPARENT] = 0.1 nmol/106 cells/day and System II (low-affinity and high-velocity), Km[APPARENT] = 3.25 × 10-5  M and VMAX[APPARENT] = 1000 nmol/106 cells/day. A third system of metabolism of AAF to AF, with Km[APPARENT] and VMAX[APPARENT] constants of 9.6 × 10-5  M and 4.7 nmol/106 cells/day, was also observed. Evidence provided in this report and its companion paper suggests selective roles and intracellular locations for System I- and System II-mediated AAF metabolite formation during hepatocarcinogenesis, although some of the molecules and mechanisms responsible for multi-system processing remain to be fully defined.

  13. Circulating dendritic cells in pediatric patients with nephrotic syndrome

    African Journals Online (AJOL)

    EL-HAKIM

    nephrotic syndrome, circulating DCs were measured by flowcytometry. Results: Circulating DC count ... parents or caregivers of each child before enrollment in the study. ..... role in initiating the primary immune response. On the basis of the ...

  14. Leach and mold resistance of essential oil metabolites

    Science.gov (United States)

    Carol A. Clausen; Vina W. Yang

    2011-01-01

    Purified primary metabolites from essential oils were previously shown to be bioactive inhibitors of mold fungi on unleached Southern pine sapwood, either alone or in synergy with a second metabolite. This study evaluated the leachability of these compounds in Southern pine that was either dip- or vacuum-treated. Following laboratory leach tests, specimens were...

  15. Development of an HIV-1 Subtype Panel in China: Isolation and Characterization of 30 HIV-1 Primary Strains Circulating in China.

    Directory of Open Access Journals (Sweden)

    Jingwan Han

    Full Text Available The complex epidemic and significant diversity of HIV-1 strains in China pose serious challenges for surveillance and diagnostic assays, vaccine development and clinical management. There is a lack of HIV-1 isolates in current canonical HIV-1 subtype panels that can represent HIV-1 diversity in China; an HIV-1 subtype panel for China is urgently needed.Blood samples were collected from HIV-1 infected patients participating in the drug-resistance surveillance program in China. The samples were isolated, cultured and stored as neat culture supernatant. The HIV-1 isolates were fully characterized. The panel was used to compare 2 viral load assays and 2 p24 assays as the examples of how this panel could be used.An HIV-1 subtype panel for China composed of 30 HIV-1 primary strains of four subtypes (B [including Thai-B], CRF01_AE, CRF07_BC and G was established. The samples were isolated and cultured to a high-titer (10(6-10(9 copies/ml/high-volume (40 ml. The HIV-1 isolates were fully characterized by the final viral load, p24 concentration, gag-pol and envC2V3 sequencing, co-receptor prediction, determination of the four amino acids at the tip of the env V3-loop, glycosylation sites in the V3 loop and the drug-resistance mutations. The comparison of two p24 assays and two viral load assays on the isolates illustrated how this panel may be used for the evaluation of diagnostic assay performance. The Pearson value between p24 assays were 0.938. The viral load results showed excellent concordance and agreement for samples of Thai-B, but lower correlations for samples of CRF01_AE.The current panel of 30 HIV-1 isolates served as a basis for the development of a comprehensive panel of fully characterized viral isolates, which could reflect the current dynamic and complex HIV-1 epidemic in China. This panel will be available to support HIV-1 research, assay evaluation, vaccine and drug development.

  16. Circulation of Stars

    Science.gov (United States)

    Boitani, P.

    2016-01-01

    Since the dawn of man, contemplation of the stars has been a primary impulse in human beings, who proliferated their knowledge of the stars all over the world. Aristotle sees this as the product of primeval and perennial “wonder” which gives rise to what we call science, philosophy, and poetry. Astronomy, astrology, and star art (painting, architecture, literature, and music) go hand in hand through millennia in all cultures of the planet (and all use catasterisms to explain certain phenomena). Some of these developments are independent of each other, i.e., they take place in one culture independently of others. Some, on the other hand, are the product of the “circulation of stars.” There are two ways of looking at this. One seeks out forms, the other concentrates on the passing of specific lore from one area to another through time. The former relies on archetypes (for instance, with catasterism), the latter constitutes a historical process. In this paper I present some of the surprising ways in which the circulation of stars has occurred—from East to West, from East to the Far East, and from West to East, at times simultaneously.

  17. Metabolites of alectinib in human: their identification and pharmacological activity

    Directory of Open Access Journals (Sweden)

    Mika Sato-Nakai

    2017-07-01

    Full Text Available Two metabolites (M4 and M1b in plasma and four metabolites (M4, M6, M1a and M1b in faeces were detected through the human ADME study following a single oral administration of [14C]alectinib, a small-molecule anaplastic lymphoma kinase inhibitor, to healthy subjects. In the present study, M1a and M1b, which chemical structures had not been identified prior to the human ADME study, were identified as isomers of a carboxylate metabolite oxidatively cleaved at the morpholine ring. In faeces, M4 and M1b were the main metabolites, which shows that the biotransformation to M4 and M1b represents two main metabolic pathways for alectinib. In plasma, M4 was a major metabolite and M1b was a minor metabolite. The contribution to in vivo pharmacological activity of these circulating metabolites was assessed from their in vitro pharmacological activity and plasma protein binding. M4 had a similar cancer cell growth inhibitory activity and plasma protein binding to that of alectinib, suggesting its contribution to the antitumor activity of alectinib, whereas the pharmacological activity of M1b was insignificant.

  18. Transportable hyperpolarized metabolites

    Science.gov (United States)

    Ji, Xiao; Bornet, Aurélien; Vuichoud, Basile; Milani, Jonas; Gajan, David; Rossini, Aaron J.; Emsley, Lyndon; Bodenhausen, Geoffrey; Jannin, Sami

    2017-01-01

    Nuclear spin hyperpolarization of 13C-labelled metabolites by dissolution dynamic nuclear polarization can enhance the NMR signals of metabolites by several orders of magnitude, which has enabled in vivo metabolic imaging by MRI. However, because of the short lifetime of the hyperpolarized magnetization (typically <1 min), the polarization process must be carried out close to the point of use. Here we introduce a concept that markedly extends hyperpolarization lifetimes and enables the transportation of hyperpolarized metabolites. The hyperpolarized sample can thus be removed from the polarizer and stored or transported for use at remote MRI or NMR sites. We show that hyperpolarization in alanine and glycine survives 16 h storage and transport, maintaining overall polarization enhancements of up to three orders of magnitude. PMID:28072398

  19. Loss of metabolites from monkey striatum during PET with FDOPA

    DEFF Research Database (Denmark)

    Cumming, P; Munk, O L; Doudet, D

    2001-01-01

    constants using data recorded during 240 min of FDOPA circulation in normal monkeys and in monkeys with unilateral 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) lesions. Use of the extended models increased the magnitudes of K(D)(i) and k(D)(3) in striatum; in the case of k(D)(3), variance...... of the estimate was substantially improved upon correction for metabolite loss. The rate constants for metabolite loss were higher in MPTP-lesioned monkey striatum than in normal striatum. The high correlation between individual estimates of k(Lin)(cl) and k(DA)(9) suggests that both rate constants reveal loss...

  20. Secondary metabolites from Ganoderma.

    Science.gov (United States)

    Baby, Sabulal; Johnson, Anil John; Govindan, Balaji

    2015-06-01

    Ganoderma is a genus of medicinal mushrooms. This review deals with secondary metabolites isolated from Ganoderma and their biological significance. Phytochemical studies over the last 40years led to the isolation of 431 secondary metabolites from various Ganoderma species. The major secondary compounds isolated are (a) C30 lanostanes (ganoderic acids), (b) C30 lanostanes (aldehydes, alcohols, esters, glycosides, lactones, ketones), (c) C27 lanostanes (lucidenic acids), (d) C27 lanostanes (alcohols, lactones, esters), (e) C24, C25 lanostanes (f) C30 pentacyclic triterpenes, (g) meroterpenoids, (h) farnesyl hydroquinones (meroterpenoids), (i) C15 sesquiterpenoids, (j) steroids, (k) alkaloids, (l) prenyl hydroquinone (m) benzofurans, (n) benzopyran-4-one derivatives and (o) benzenoid derivatives. Ganoderma lucidum is the species extensively studied for its secondary metabolites and biological activities. Ganoderma applanatum, Ganoderma colossum, Ganoderma sinense, Ganoderma cochlear, Ganoderma tsugae, Ganoderma amboinense, Ganoderma orbiforme, Ganoderma resinaceum, Ganoderma hainanense, Ganoderma concinna, Ganoderma pfeifferi, Ganoderma neo-japonicum, Ganoderma tropicum, Ganoderma australe, Ganoderma carnosum, Ganoderma fornicatum, Ganoderma lipsiense (synonym G. applanatum), Ganoderma mastoporum, Ganoderma theaecolum, Ganoderma boninense, Ganoderma capense and Ganoderma annulare are the other Ganoderma species subjected to phytochemical studies. Further phytochemical studies on Ganoderma could lead to the discovery of hitherto unknown biologically active secondary metabolites. Copyright © 2015 Elsevier Ltd. All rights reserved.

  1. Metabolite Damage and Metabolite Damage Control in Plants

    Energy Technology Data Exchange (ETDEWEB)

    Hanson, Andrew D. [Horticultural Sciences Department and; Henry, Christopher S. [Mathematics and Computer Science Division, Argonne National Laboratory, Argonne, Illinois 60439, email:; Computation Institute, University of Chicago, Chicago, Illinois 60637; Fiehn, Oliver [Genome Center, University of California, Davis, California 95616, email:; de Crécy-Lagard, Valérie [Microbiology and Cell Science Department, University of Florida, Gainesville, Florida 32611, email: ,

    2016-04-29

    It is increasingly clear that (a) many metabolites undergo spontaneous or enzyme-catalyzed side reactions in vivo, (b) the damaged metabolites formed by these reactions can be harmful, and (c) organisms have biochemical systems that limit the buildup of damaged metabolites. These damage-control systems either return a damaged molecule to its pristine state (metabolite repair) or convert harmful molecules to harmless ones (damage preemption). Because all organisms share a core set of metabolites that suffer the same chemical and enzymatic damage reactions, certain damage-control systems are widely conserved across the kingdoms of life. Relatively few damage reactions and damage-control systems are well known. Uncovering new damage reactions and identifying the corresponding damaged metabolites, damage-control genes, and enzymes demands a coordinated mix of chemistry, metabolomics, cheminformatics, biochemistry, and comparative genomics. This review illustrates the above points using examples from plants, which are at least as prone to metabolite damage as other organisms.

  2. Ação da adenosina na circulação pulmonar de pacientes com hipertensão pulmonar primária Effect of adenosine on pulmonary circulation in patients with primary pulmonary hypertension

    Directory of Open Access Journals (Sweden)

    Rogerio Souza

    2005-02-01

    . Although its effect on the pulmonary arteries is well known, its influence on capillaries and veins has yet to be described. OBJECTIVE: To evaluate the pre- and post-administration effects of adenosine on arterial and venous resistance in the pulmonary circulation of patients with primary pulmonary hypertension. METHOD: The study involved 7 patients with primary pulmonary hypertension and presenting a positive response to adenosine on the acute test. Before and after adenosine administration, arterial and venous resistances were determined by estimating pulmonary capillary pressure through analysis of pulmonary artery pressure decay curves. RESULTS: Following adenosine administration, there was an increase in the cardiac index (from 1.71 ± 0.23 to 2.72 ± 0.74 L/min-1/m-2 and a decrease in pulmonary vascular resistance (from 2924 ± 1060 to 1975 ± 764 dynes/s/cm-5/m-2 with no significant variations in mean pulmonary artery pressure (pre: 75.6 ± 16.8 mmHg; post: 78.1 ± 18.8 mmHg, pulmonary wedge pressure (pre: 15.3 ± 1.5 mmHg; post: 15.4 ± 1.9 mmHg and pulmonary capillary pressure (pre: 43.8 ± 5.8 mmHg; post: 44.5 ± 4.9 mmHg. The ratio between arterial resistance and total pulmonary vascular resistance also presented a less than significant variation (pre: 50 ± 15%; post: 49 ± 17%. These findings suggest that adenosine affects the capillaries and veins as well as the arteries. CONCLUSION: We can conclude that the adenosine mechanism is not restricted to the arterial aspect of the pulmonary circulation, and that analysis of pulmonary capillary pressure could prove useful in the study of various drugs that affect the pulmonary circulation.

  3. Microwave circulator design

    CERN Document Server

    Linkhart, Douglas K

    2014-01-01

    Circulator design has advanced significantly since the first edition of this book was published 25 years ago. The objective of this second edition is to present theory, information, and design procedures that will enable microwave engineers and technicians to design and build circulators successfully. This resource contains a discussion of the various units used in the circulator design computations, as well as covers the theory of operation. This book presents numerous applications, giving microwave engineers new ideas about how to solve problems using circulators. Design examples are provided, which demonstrate how to apply the information to real-world design tasks.

  4. Urinary excretion of androgen metabolites, comparison with excretion of radioactive metabolites after injection of [4-14C]testosterone

    International Nuclear Information System (INIS)

    Deslypere, J.P.; Sayed, A.; Vermeulen, A.; Wiers, P.W.

    1981-01-01

    The influence of age on the metabolic pattern of [4- 14 C]testosterone was studied in 20 young and 8 elderly males and compared to the metabolic pattern of endogenous androgens; the latter was also studied in 16 young and 8 elderly women. In both young and elderly males, androsterone and aetiocholanolone glucuronide represent 65% of [4- 14 C]testosterone metabolites: together with their suephoconjugates as well as with 5α- and 5β-androstane-3α, 17β-diol they represent even more than 75% of total urinary metabolites. The 5α/5β ratio of metabolites of [4- 14 C]testosterone was significantly (P 14 C]testosterone metabolites was generally higher than the ratio of metabolites of endogenous androgens, suggesting that the transformation of T to ring A saturated metabolites occurs at least partially in another compartment than the transformation of DHEA to these metabolites. For both [4- 14 C]testosterone and endogenous androgen metabolites we observed a statistically significant reduction of the 5α/5β ratio with age, a general phenomenon in both males and females. This reduction concern also 11-OH-androst-4-ene-3.17-dione metabolism. Neither sex hormone levels, nor specific binding seems to determine this age dependent shift; neither is there convincing evidence for latent hypothyroisism or liver dysfunction in the elderly. An age associated primary decrease of the 5α-reductase activity seems the most likely explanation. (author)

  5. Investigation of metabolites for estimating blood deposition time.

    Science.gov (United States)

    Lech, Karolina; Liu, Fan; Davies, Sarah K; Ackermann, Katrin; Ang, Joo Ern; Middleton, Benita; Revell, Victoria L; Raynaud, Florence J; Hoveijn, Igor; Hut, Roelof A; Skene, Debra J; Kayser, Manfred

    2018-01-01

    Trace deposition timing reflects a novel concept in forensic molecular biology involving the use of rhythmic biomarkers for estimating the time within a 24-h day/night cycle a human biological sample was left at the crime scene, which in principle allows verifying a sample donor's alibi. Previously, we introduced two circadian hormones for trace deposition timing and recently demonstrated that messenger RNA (mRNA) biomarkers significantly improve time prediction accuracy. Here, we investigate the suitability of metabolites measured using a targeted metabolomics approach, for trace deposition timing. Analysis of 171 plasma metabolites collected around the clock at 2-h intervals for 36 h from 12 male participants under controlled laboratory conditions identified 56 metabolites showing statistically significant oscillations, with peak times falling into three day/night time categories: morning/noon, afternoon/evening and night/early morning. Time prediction modelling identified 10 independently contributing metabolite biomarkers, which together achieved prediction accuracies expressed as AUC of 0.81, 0.86 and 0.90 for these three time categories respectively. Combining metabolites with previously established hormone and mRNA biomarkers in time prediction modelling resulted in an improved prediction accuracy reaching AUCs of 0.85, 0.89 and 0.96 respectively. The additional impact of metabolite biomarkers, however, was rather minor as the previously established model with melatonin, cortisol and three mRNA biomarkers achieved AUC values of 0.88, 0.88 and 0.95 for the same three time categories respectively. Nevertheless, the selected metabolites could become practically useful in scenarios where RNA marker information is unavailable such as due to RNA degradation. This is the first metabolomics study investigating circulating metabolites for trace deposition timing, and more work is needed to fully establish their usefulness for this forensic purpose.

  6. Arachidonic acid metabolites and endothelial dysfunction of portal hypertension.

    Science.gov (United States)

    Sacerdoti, David; Pesce, Paola; Di Pascoli, Marco; Brocco, Silvia; Cecchetto, Lara; Bolognesi, Massimo

    2015-07-01

    Increased resistance to portal flow and increased portal inflow due to mesenteric vasodilatation represent the main factors causing portal hypertension in cirrhosis. Endothelial cell dysfunction, defined as an imbalance between the synthesis, release, and effect of endothelial mediators of vascular tone, inflammation, thrombosis, and angiogenesis, plays a major role in the increase of resistance in portal circulation, in the decrease in the mesenteric one, in the development of collateral circulation. Reduced response to vasodilators in liver sinusoids and increased response in the mesenteric arterioles, and, viceversa, increased response to vasoconstrictors in the portal-sinusoidal circulation and decreased response in the mesenteric arterioles are also relevant to the pathophysiology of portal hypertension. Arachidonic acid (AA) metabolites through the three pathways, cyclooxygenase (COX), lipoxygenase, and cytochrome P450 monooxygenase and epoxygenase, are involved in endothelial dysfunction of portal hypertension. Increased thromboxane-A2 production by liver sinusoidal endothelial cells (LSECs) via increased COX-1 activity/expression, increased leukotriens, increased epoxyeicosatrienoic acids (EETs) (dilators of the peripheral arterial circulation, but vasoconstrictors of the portal-sinusoidal circulation), represent a major component in the increased portal resistance, in the decreased portal response to vasodilators and in the hyper-response to vasoconstrictors. Increased prostacyclin (PGI2) via COX-1 and COX-2 overexpression, and increased EETs/heme-oxygenase-1/K channels/gap junctions (endothelial derived hyperpolarizing factor system) play a major role in mesenteric vasodilatation, hyporeactivity to vasoconstrictors, and hyper-response to vasodilators. EETs, mediators of liver regeneration after hepatectomy and of angiogenesis, may play a role in the development of regenerative nodules and collateral circulation, through stimulation of vascular endothelial

  7. Periodontitis and increase in circulating oxidative stress

    Directory of Open Access Journals (Sweden)

    Takaaki Tomofuji

    2009-05-01

    Full Text Available Reactive oxygen species (ROS are products of normal cellular metabolism. However, excessive production of ROS oxidizes DNA, lipids and proteins, inducing tissue damage. Studies have shown that periodontitis induces excessive ROS production in periodontal tissue. When periodontitis develops, ROS produced in the periodontal lesion diffuse into the blood stream, resulting in the oxidation of blood molecules (circulating oxidative stress. Such oxidation may be detrimental to systemic health. For instance, previous animal studies suggested that experimental periodontitis induces oxidative damage of the liver and descending aorta by increasing circulating oxidative stress. In addition, it has been revealed that clinical parameters in chronic periodontitis patients showed a significant improvement 2 months after periodontal treatment, which was accompanied by a significant reduction of reactive oxygen metabolites in plasma. Improvement of periodontitis by periodontal treatment could reduce the occurrence of circulating oxidative stress. Furthermore, recent studies indicate that the increase in circulating oxidative stress following diabetes mellitus and inappropriate nutrition damages periodontal tissues. In such cases, therapeutic approaches to systemic oxidative stress might be necessary to improve periodontal health.

  8. Vasculitis of the mesenteric circulation.

    Science.gov (United States)

    Koster, Matthew J; Warrington, Kenneth J

    2017-02-01

    Vasculitis of the mesenteric circulation is an uncommon but life-threatening manifestation of systemic vasculitis. Initial symptoms are frequently non-specific and therefore patients often present to primary care physicians and gastroenterologists with abdominal pain or gastrointestinal bleeding. Given the severity of the conditions associated with mesenteric vasculitis, it is imperative to appropriately diagnose and initiate treatment of suspected cases. This review will focus on diseases commonly associated with vasculitis of the mesenteric vessels. Imaging characteristics and clinical features assisting in diagnosis as well as initial approaches to treatment are emphasized. Copyright © 2016 Elsevier Ltd. All rights reserved.

  9. Autonomic Regulation of Splanchnic Circulation

    Directory of Open Access Journals (Sweden)

    Kathleen A Fraser

    1991-01-01

    Full Text Available The role of the autonomic nervous system in circulatory regulation of the splanchnic organs (stomach, small intestine, colon, liver, pancreas and spleen is reviewed. In general, the sympathetic nervous system is primarily involved in vasoconstriction, while the parasympathetic contributes to vasodilation. Vasoconstriction in the splanchnic circulation appears to be mediated by alpha-2 receptors and vasodilation by activation of primary afferent nerves with subsequent release of vasodilatory peptides, or by stimulation of beta-adrenergic receptors. As well, an important function of the autonomic nervous system is to provide a mechanism by which splanchnic vascular reserve can be mobilized during stress to maintain overall cardiovascular homeostasis.

  10. Circulation pump mounting

    International Nuclear Information System (INIS)

    Skalicky, A.

    1976-01-01

    The suspension is described of nuclear reactor circulating pumps enabling their dilatation with a minimum reverse force consisting of spacing rods supported with one end in the anchor joints and provided with springs and screw joints engaging the circulating pump shoes. The spacing rods are equipped with side vibration dampers anchored in the shaft side wall and on the body of the circulating pump drive body. The negative reverse force F of the spacing rods is given by the relation F=Q/l.y, where Q is the weight of the circulating pump, l is the spatial distance between the shoe joints and anchor joints, and y is the deflection of the circulating pump vertical axis from the mean equilibrium position. The described suspension is advantageous in that that the reverse force for the deflection from the mean equilibrium position is minimal, dynamic behaviour is better, and construction costs are lower compared to suspension design used so far. (J.B.)

  11. Production of Metabolites

    DEFF Research Database (Denmark)

    2011-01-01

    A recombinant micro-organism such as Saccharomyces cerevisiae which produces and excretes into culture medium a stilbenoid metabolite product when grown under stilbenoid production conditions, which expresses in above native levels a ABC transporter which transports said stilbenoid out of said...... micro-organism cells to the culture medium. The genome of the Saccharomyces cerevisiae produces an auxotrophic phenotype which is compensated by a plasmid which also expresses one or more of said enzymes constituting said metabolic pathway producing said stilbenoid, an expression product of the plasmid...

  12. Seasonal overturning circulation in the Red Sea: 2. Winter circulation

    KAUST Repository

    Yao, Fengchao; Hoteit, Ibrahim; Pratt, Lawrence J.; Bower, Amy S.; Kö hl, Armin; Gopalakrishnan, Ganesh; Rivas, David

    2014-01-01

    The shallow winter overturning circulation in the Red Sea is studied using a 50 year high-resolution MITgcm (MIT general circulation model) simulation with realistic atmospheric forcing. The overturning circulation for a typical year, represented

  13. Mutagenic azide metabolite is azidoalanine

    International Nuclear Information System (INIS)

    Owais, W.M.; Rosichan, J.L.; Ronald, R.C.; Kleinhofs, A.; Nilan, R.A.

    1981-01-01

    Sodium axide produces high mutation rates in a number of species. Azide mutagenicity is mediated through a metabolite in barley and bacteria. Many studies showed that azide affects the L-cysteine biosynthesis pathway. Cell-free extracts of Salmonella typhimurium convert azide and O-acetylserine to the mutagenic metabolite. O-acetylserine sulfhydrylase was identified as the enzyme responsible for the metabolite biosynthesis. To confirm the conclusion that the azide metabolite is formed through the β-substitution pathway of L-cysteine, we radioactively labeled the azide metabolite using 14 C-labeled precursors. Moreover, the mutagenic azide metabolite was purified and identified as azidoalanine based on mass spectroscopy and elemental analysis. 26 refs., 3 figs., 1 tab

  14. Evaluation of chlorpyrifos toxicity through a 28-day study: Cholinesterase activity, oxidative stress responses, parent compound/metabolite levels, and primary DNA damage in blood and brain tissue of adult male Wistar rats.

    Science.gov (United States)

    Kopjar, Nevenka; Žunec, Suzana; Mendaš, Gordana; Micek, Vedran; Kašuba, Vilena; Mikolić, Anja; Lovaković, Blanka Tariba; Milić, Mirta; Pavičić, Ivan; Čermak, Ana Marija Marjanović; Pizent, Alica; Lucić Vrdoljak, Ana; Želježić, Davor

    2018-01-05

    In this 28 day-study, we evaluated the effects of the insecticide chlorpyrifos orally administered to Wistar rats at doses 0.160, 0.015, and 0.010 mg/kg b. w./day. Following treatment, total cholinesterase activity and activities of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) were measured. Oxidative stress responses were evaluated using a battery of endpoints to establish lipid peroxidation, changes in total antioxidant capacity, level of reactive oxygen species (ROS), glutathione (GSH) level and activities of glutathione peroxidase (GSH-Px), superoxide dismutase (SOD) and catalase. Using HPLC-UV DAD analysis, levels of the parent compound and its main metabolite 3,5,6-trichloro-2-pyridinol in plasma and brain tissue were measured. The genotoxic effect was estimated using alkaline comet assay in leukocytes and brain tissue. The exposure did not result in significant effects on total cholinesterase, AChE and BChE activity in plasma and brain tissue. Lipid peroxidation slightly increased both in plasma and brain tissue. Total antioxidant capacity, ROS and GSH levels were marginally influenced by the exposure. Treatment led to significant increases of GSH-Px activity in blood, SOD activity in erythrocytes and a slight increase of catalase activity in plasma. HPLC-UV DAD analysis revealed the presence of both the parent compound and its main metabolite in the plasma of all of the experimental animals and brain tissue of the animals treated at the two higher doses. All of the tested doses of chlorpyrifos were slightly genotoxic, both to leukocytes and brain tissue. Our results call for further research using other sensitive biomarkers of effect, along with different exposure scenarios. Copyright © 2017 Elsevier B.V. All rights reserved.

  15. Metabolite ratios as potential biomarkers for type 2 diabetes: a DIRECT study

    DEFF Research Database (Denmark)

    Molnos, Sophie; Wahl, Simone; Haid, Mark

    2018-01-01

    ) and arginine stimulation. We then investigated if the identified metabolite ratios were associated with measures of OGTT-derived beta cell function and with prevalent and incident type 2 diabetes. Methods: We measured the levels of 188 metabolites in plasma samples from 130 healthy members of twin families......Aims/hypothesis: Circulating metabolites have been shown to reflect metabolic changes during the development of type 2 diabetes. In this study we examined the association of metabolite levels and pairwise metabolite ratios with insulin responses after glucose, glucagon-like peptide-1 (GLP-1...... (from the Netherlands Twin Register) at five time points during a modified 3 h hyperglycaemic clamp with glucose, GLP-1 and arginine stimulation. We validated our results in cohorts with OGTT data (n = 340) and epidemiological case–control studies of prevalent (n = 4925) and incident (n = 4277...

  16. Methodological considerations for measuring glucocorticoid metabolites in feathers

    Science.gov (United States)

    Berk, Sara A.; McGettrick, Julie R.; Hansen, Warren K.; Breuner, Creagh W.

    2016-01-01

    In recent years, researchers have begun to use corticosteroid metabolites in feathers (fCORT) as a metric of stress physiology in birds. However, there remain substantial questions about how to measure fCORT most accurately. Notably, small samples contain artificially high amounts of fCORT per millimetre of feather (the small sample artefact). Furthermore, it appears that fCORT is correlated with circulating plasma corticosterone only when levels are artificially elevated by the use of corticosterone implants. Here, we used several approaches to address current methodological issues with the measurement of fCORT. First, we verified that the small sample artefact exists across species and feather types. Second, we attempted to correct for this effect by increasing the amount of methanol relative to the amount of feather during extraction. We consistently detected more fCORT per millimetre or per milligram of feather in small samples than in large samples even when we adjusted methanol:feather concentrations. We also used high-performance liquid chromatography to identify hormone metabolites present in feathers and measured the reactivity of these metabolites against the most commonly used antibody for measuring fCORT. We verified that our antibody is mainly identifying corticosterone (CORT) in feathers, but other metabolites have significant cross-reactivity. Lastly, we measured faecal glucocorticoid metabolites in house sparrows and correlated these measurements with corticosteroid metabolites deposited in concurrently grown feathers; we found no correlation between faecal glucocorticoid metabolites and fCORT. We suggest that researchers should be cautious in their interpretation of fCORT in wild birds and should seek alternative validation methods to examine species-specific relationships between environmental challenges and fCORT. PMID:27335650

  17. Benzene: a case study in parent chemical and metabolite interactions.

    Science.gov (United States)

    Medinsky, M A; Kenyon, E M; Schlosser, P M

    1995-12-28

    Benzene, an important industrial solvent, is also present in unleaded gasoline and cigarette smoke. The hematotoxic effects of benzene in humans are well documented and include aplastic anemia and pancytopenia, and acute myelogenous leukemia. A combination of metabolites (hydroquinone and phenol for example) is apparently necessary to duplicate the hematotoxic effect of benzene, perhaps due in part to the synergistic effect of phenol on myeloperoxidase-mediated oxidation of hydroquinone to the reactive metabolite benzoquinone. Since benzene and its hydroxylated metabolites (phenol, hydroquinone and catechol) are substrates for the same cytochrome P450 enzymes, competitive interactions among the metabolites are possible. In vivo data on metabolite formation by mice exposed to various benzene concentrations are consistent with competitive inhibition of phenol oxidation by benzene. In vitro studies of the metabolic oxidation of benzene, phenol and hydroquinone are consistent with the mechanism of competitive interaction among the metabolites. The dosimetry of benzene and its metabolites in the target tissue, bone marrow, depends on the balance of activation processes such as enzymatic oxidation and deactivation processes such as conjugation and excretion. Phenol, the primary benzene metabolite, can undergo both oxidation and conjugation. Thus, the potential exists for competition among various enzymes for phenol. However, zonal localization of Phase I and Phase II enzymes in various regions of the liver acinus regulates this competition. Biologically-based dosimetry models that incorporate the important determinants of benzene flux, including interactions with other chemicals, will enable prediction of target tissue doses of benzene and metabolites at low exposure concentrations relevant for humans.

  18. Immune regulation by microbiome metabolites.

    Science.gov (United States)

    Kim, Chang H

    2018-03-22

    Commensal microbes and the host immune system have been co-evolved for mutual regulation. Microbes regulate the host immune system, in part, by producing metabolites. A mounting body of evidence indicates that diverse microbial metabolites profoundly regulate the immune system via host receptors and other target molecules. Immune cells express metabolite-specific receptors such as P2X 7 , GPR41, GPR43, GPR109A, aryl hydrocarbon receptor precursor (AhR), pregnane X receptor (PXR), farnesoid X receptor (FXR), TGR5 and other molecular targets. Microbial metabolites and their receptors form an extensive array of signals to respond to changes in nutrition, health and immunological status. As a consequence, microbial metabolite signals contribute to nutrient harvest from diet, and regulate host metabolism and the immune system. Importantly, microbial metabolites bidirectionally function to promote both tolerance and immunity to effectively fight infection without developing inflammatory diseases. In pathogenic conditions, adverse effects of microbial metabolites have been observed as well. Key immune-regulatory functions of the metabolites, generated from carbohydrates, proteins and bile acids, are reviewed in this article. © 2018 John Wiley & Sons Ltd.

  19. Mass Spectrometric Method for Analyzing Metabolites in Yeast with Single Cell Sensitivity

    NARCIS (Netherlands)

    Amantonico, Andrea; Oh, Joo Yeon; Sobek, Jens; Heinemann, Matthias; Zenobi, Renato

    2008-01-01

    Getting a look-in: An optimized MALDI-MS procedure has been developed to detect endogenous primary metabolites directly in the cell extract. A detection limit corresponding to metabolites from less than a single cell has been attained, opening the door to single-cell metabolomics by mass

  20. Bignoniaceae Metabolites as Semiochemicals

    Directory of Open Access Journals (Sweden)

    Lucía Castillo

    2010-10-01

    Full Text Available Members of the family Bignoniaceae are mostly found in tropical and neo-tropical regions in America, Asia and Africa, although some of them are cultivated in other regions as ornamentals. Species belonging to this family have been extensively studied in regard to their pharmacological properties (as extracts and isolated compounds. The aim of this review is to summarize the reported scientific evidence about the chemical properties as well as that of the extracts and isolated compounds from species of this family, focusing mainly in insect-plant interactions. As it is known, this family is recognized for the presence of iridoids which are markers of oviposition and feeding preference to species which have became specialist feeders. Some herbivore species have also evolved to the point of been able to sequester iridoids and use them as defenses against their predators. However, iridoids also exhibit anti-insect properties, and therefore they may be good lead molecules to develop botanical pesticides. Other secondary metabolites, such as quinones, and whole extracts have also shown potential as anti-insect agents.

  1. Role of secondary metabolites/antioxidants in vitro

    Science.gov (United States)

    In literature, secondary metabolites are described as natural products, waste, phytopharmaceuticals, bioactive constituents or by-products of the primary metabolism. They occur in many plant genera and microorganisms in vivo and in vitro, and have complex chemical structures specific to the plants w...

  2. Arctic circulation regimes.

    Science.gov (United States)

    Proshutinsky, Andrey; Dukhovskoy, Dmitry; Timmermans, Mary-Louise; Krishfield, Richard; Bamber, Jonathan L

    2015-10-13

    Between 1948 and 1996, mean annual environmental parameters in the Arctic experienced a well-pronounced decadal variability with two basic circulation patterns: cyclonic and anticyclonic alternating at 5 to 7 year intervals. During cyclonic regimes, low sea-level atmospheric pressure (SLP) dominated over the Arctic Ocean driving sea ice and the upper ocean counterclockwise; the Arctic atmosphere was relatively warm and humid, and freshwater flux from the Arctic Ocean towards the subarctic seas was intensified. By contrast, during anticylonic circulation regimes, high SLP dominated driving sea ice and the upper ocean clockwise. Meanwhile, the atmosphere was cold and dry and the freshwater flux from the Arctic to the subarctic seas was reduced. Since 1997, however, the Arctic system has been under the influence of an anticyclonic circulation regime (17 years) with a set of environmental parameters that are atypical for this regime. We discuss a hypothesis explaining the causes and mechanisms regulating the intensity and duration of Arctic circulation regimes, and speculate how changes in freshwater fluxes from the Arctic Ocean and Greenland impact environmental conditions and interrupt their decadal variability. © 2015 The Authors.

  3. Secondary metabolites from marine microorganisms.

    Science.gov (United States)

    Kelecom, Alphonse

    2002-03-01

    After 40 years of intensive research, chemistry of marine natural products has become a mature field. Since 1995, there are signals of decreased interest in the search of new metabolites from traditional sources such as macroalgae and octocorals, and the number of annual reports on marine sponges stabilized. On the contrary, metabolites from microorganisms is a rapidly growing field, due, at least in part, to the suspicion that a number of metabolites obtained from algae and invertebrates may be produced by associated microorganisms. Studies are concerned with bacteria and fungi, isolated from seawater, sediments, algae, fish and mainly from marine invertebrates such as sponges, mollusks, tunicates, coelenterates and crustaceans. Although it is still to early to define tendencies, it may be stated that the metabolites from microorganisms are in most cases quite different from those produced by the invertebrate hosts. Nitrogenated metabolites predominate over acetate derivatives, and terpenes are uncommon. Among the latter, sesquiterpenes, diterpenes and carotenes have been isolated; among nitrogenated metabolites, amides, cyclic peptides and indole alkaloids predominate.

  4. Secondary metabolites from marine microorganisms

    Directory of Open Access Journals (Sweden)

    KELECOM ALPHONSE

    2002-01-01

    Full Text Available After 40 years of intensive research, chemistry of marine natural products has become a mature field. Since 1995, there are signals of decreased interest in the search of new metabolites from traditional sources such as macroalgae and octocorals, and the number of annual reports on marine sponges stabilized. On the contrary, metabolites from microorganisms is a rapidly growing field, due, at least in part, to the suspicion that a number of metabolites obtained from algae and invertebrates may be produced by associated microorganisms. Studies are concerned with bacteria and fungi, isolated from seawater, sediments, algae, fish and mainly from marine invertebrates such as sponges, mollusks, tunicates, coelenterates and crustaceans. Although it is still to early to define tendencies, it may be stated that the metabolites from microorganisms are in most cases quite different from those produced by the invertebrate hosts. Nitrogenated metabolites predominate over acetate derivatives, and terpenes are uncommon. Among the latter, sesquiterpenes, diterpenes and carotenes have been isolated; among nitrogenated metabolites, amides, cyclic peptides and indole alkaloids predominate.

  5. Metabolite profiling of recombinant CHO cells: Designing tailored feeding regimes that enhance recombinant antibody production.

    NARCIS (Netherlands)

    Sellick, C.A.; Croxford, A.S.; Maqsood, A.R.; Stephens, G.; Westerhoff, H.V.; Goodacre, R.; Dickson, A.J.

    2011-01-01

    Chinese hamster ovary (CHO) cells are the primary platform for commercial expression of recombinant therapeutic proteins. Obtaining maximum production from the expression platform requires optimal cell culture medium (and associated nutrient feeds). We have used metabolite profiling to define the

  6. Metabolite profiling of recombinant CHO cells: designing tailored feeding regimes that enhance recombinant antibody production.

    NARCIS (Netherlands)

    Sellick, C.A.; Croxford, A.S.; Maqsood, A.R.; Stephens, G.; Westerhoff, H.V.; Goodacre, R.; Dickson, A.J.

    2011-01-01

    Chinese hamster ovary (CHO) cells are the primary platform for commercial expression of recombinant therapeutic proteins. Obtaining maximum production from the expression platform requires optimal cell culture medium (and associated nutrient feeds). We have used metabolite profiling to define the

  7. Controlled humidity gas circulators

    International Nuclear Information System (INIS)

    Gruner, S.M.

    1981-01-01

    A programmable circulator capable of regulating the humidity of a gas stream over a wide range of humidity is described. An optical dew-point hygrometer is used as a feedback element to control the addition or removal of water vapor. Typical regulation of the gas is to a dew-point temperature of +- 0.2 0 C and to an accuracy limited by the dew-point hygrometer

  8. Fluid circulation control device

    International Nuclear Information System (INIS)

    Benard, Henri; Henocque, Jean.

    1982-01-01

    Horizontal fluid circulation control device, of the type having a pivoting flap. This device is intended for being fitted in the pipes of hydraulic installation, particularly in a bleed and venting system of a nuclear power station shifting radioactive or contaminated liquids. The characteristic of this device is the cut-out at the top of the flap to allow the air contained in the pipes to flow freely [fr

  9. Experimental study of natural circulation circuit

    Energy Technology Data Exchange (ETDEWEB)

    Lemos, Wanderley F.; Su, Jian, E-mail: wlemos@lasme.coppe.ufrj.br, E-mail: sujian@lasme.coppe.ufrj.br [Coordenacao dos Programas de Pos-Graduacao de Engenharia (LASME/COPPE/UFRJ), Rio de Janeiro, RJ (Brazil). Lab. de Simulacao e Metodos Numericos; Faccini, Jose L.H., E-mail: faccini@ien.gov.br [Instituto de Engenharia Nuclear (LTE/IEN/CNEN-RJ), Rio de Janeiro, RJ (Brazil). Lab. de Termo-Hidraulica Experimental

    2011-07-01

    This work presents an experimental study about fluid flows behavior in natural circulation, under conditions of single-phase flow. The experiment was performed through experimental thermal-hydraulic circuit built at IEN. This test equipment has performance similar to passive system of residual heat removal present in Advanced Pressurized Water Reactors (APWR). This experimental study aims to observing and analyzing the natural circulation phenomenon, using this experimental circuit that was dimensioned and built based on concepts of similarity and scale. This philosophy allows the analysis of natural circulation behavior in single-phase flow conditions proportionally to the functioning real conditions of a nuclear reactor. The experiment was performed through procedures to initialization of hydraulic feeding of primary and secondary circuits and electrical energizing of resistors installed inside heater. Power controller has availability to adjust values of electrical power to feeding resistors, in order to portray several conditions of energy decay of nuclear reactor in a steady state. Data acquisition system allows the measurement and monitoring of the evolution of the temperature in various points through thermocouples installed in strategic points along hydraulic circuit. The behavior of the natural circulation phenomenon was monitored by graphical interface on computer screen, showing the temperature evolutions of measuring points and results stored in digital spreadsheets. The results stored in digital spreadsheets allowed the getting of data to graphic construction and discussion about natural circulation phenomenon. Finally, the calculus of Reynolds number allowed the establishment for a correlation of friction in function of geometric scales of length, heights and cross section of tubing, considering a natural circulation flow throughout in the region of hot leg. (author)

  10. Experimental study of natural circulation circuit

    International Nuclear Information System (INIS)

    Lemos, Wanderley F.; Su, Jian; Faccini, Jose L.H.

    2011-01-01

    This work presents an experimental study about fluid flows behavior in natural circulation, under conditions of single-phase flow. The experiment was performed through experimental thermal-hydraulic circuit built at IEN. This test equipment has performance similar to passive system of residual heat removal present in Advanced Pressurized Water Reactors (APWR). This experimental study aims to observing and analyzing the natural circulation phenomenon, using this experimental circuit that was dimensioned and built based on concepts of similarity and scale. This philosophy allows the analysis of natural circulation behavior in single-phase flow conditions proportionally to the functioning real conditions of a nuclear reactor. The experiment was performed through procedures to initialization of hydraulic feeding of primary and secondary circuits and electrical energizing of resistors installed inside heater. Power controller has availability to adjust values of electrical power to feeding resistors, in order to portray several conditions of energy decay of nuclear reactor in a steady state. Data acquisition system allows the measurement and monitoring of the evolution of the temperature in various points through thermocouples installed in strategic points along hydraulic circuit. The behavior of the natural circulation phenomenon was monitored by graphical interface on computer screen, showing the temperature evolutions of measuring points and results stored in digital spreadsheets. The results stored in digital spreadsheets allowed the getting of data to graphic construction and discussion about natural circulation phenomenon. Finally, the calculus of Reynolds number allowed the establishment for a correlation of friction in function of geometric scales of length, heights and cross section of tubing, considering a natural circulation flow throughout in the region of hot leg. (author)

  11. Natural circulation cooling in a PWR geometry under accident-induced conditions

    International Nuclear Information System (INIS)

    Shimeck, D.J.; Johnsen, G.W.

    1983-01-01

    The characteristics and limits of natural circulation heat rejection over a wide range of conditions were experimentally investigated in a small-scale model of a pressurized water reactor. Conditions that were varied included primary and secondary coolant inventory, decay heat power, and primary noncondensable gas content. The results have defined three distinct modes of natural circulation, their limits and transition points, and the characteristic signatures accompanying natural circulation behavior. Particular emphasis is focused on the limits of natural circulation under severely degraded primary and secondary conditions

  12. Natural Circulation Characteristics of an Integral Pressurized Water Reactor

    International Nuclear Information System (INIS)

    Junli Gou; Suizheng Qiu; Guanghui Su; Dounan Jia

    2006-01-01

    Natural circulation potential is of great importance to the inherent safety of a nuclear reactor. This paper presents a theoretical investigation on the natural circulation characteristics of an integrated pressurized water reactor. Through numerically solved the one-dimensional model, the steady-state single phase conservative equations for the primary circuit and the steady-state two-phase drift-flux conservative equations for the secondary side of the once-through steam generator, the natural circulation characteristics are studied. Based on the preliminary calculation analysis, it is found that natural circulation mass flow rate is proportional to the exponential function of the power, and the value of the exponent is related to working conditions of the steam generator secondary side. The higher height difference between the core center and the steam generator center is favorable to the heat removal capacity of the natural circulation. (authors)

  13. Secondary metabolites from Eremostachys laciniata

    DEFF Research Database (Denmark)

    Calis, Ihsan; Güvenc, Aysegül; Armagan, Metin

    2008-01-01

    ), and forsythoside B (18), and five flavone derivatives, luteolin (19), luteolin 7-O-β-D-glucopyranoside (20), luteolin 7-O-(6''-O-β-D-apiofuranosyl)-β-D-glucopyranoside (21), apigenin 7-O-β-D-glucopyranoside (22), and apigenin 7-O-(6''-O-p-coumaroyl)-β-D-glucopyranoside (23). The structures of the metabolites were...... elucidated from spectroscopic (UV, IR, 1D- and 2D-NMR) and ESI-MS evidence, as well as from their specific optical rotation. The presence of these metabolites of three different classes strongly supports the close relationship of the genera Eremostachys and Phlomis....

  14. Metabolomic markers of fatigue: Association between circulating metabolome and fatigue in women with chronic widespread pain.

    Science.gov (United States)

    Freidin, Maxim B; Wells, Helena R R; Potter, Tilly; Livshits, Gregory; Menni, Cristina; Williams, Frances M K

    2018-02-01

    Fatigue is a sensation of unbearable tiredness that frequently accompanies chronic widespread musculoskeletal pain (CWP) and inflammatory joint disease. Its mechanisms are poorly understood and there is a lack of effective biomarkers for diagnosis and onset prediction. We studied the circulating metabolome in a population sample characterised for CWP to identify biomarkers showing specificity for fatigue. Untargeted metabolomic profiling was conducted on fasting plasma and serum samples of 1106 females with and without CWP from the TwinsUK cohort. Linear mixed-effects models accounting for covariates were used to determine relationships between fatigue and metabolites. Receiver operating curve (ROC)-analysis was used to determine predictive value of metabolites for fatigue. While no association between fatigue and metabolites was identified in twins without CWP (n=711), in participants with CWP (n=395), levels of eicosapentaenoate (EPA) ω-3 fatty acid were significantly reduced in those with fatigue (β=-0.452±0.116; p=1.2×10 -4 ). A significant association between fatigue and two other metabolites also emerged when BMI was excluded from the model: 3-carboxy-4-methyl-5-propyl-2-furanpropanoate (CMPF), and C-glycosyltryptophan (p=1.5×10 -4 and p=3.1×10 -4 , respectively). ROC analysis has identified a combination of 15 circulating metabolites with good predictive potential for fatigue in CWP (AUC=75%; 95% CI 69-80%). The results of this agnostic metabolomics screening show that fatigue is metabolically distinct from CWP, and is associated with a decrease in circulating levels of EPA. Our panel of circulating metabolites provides the starting point for a diagnostic test for fatigue in CWP. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  15. Natural Circulation Characteristics of a Symmetric Loop under Inclined Conditions

    Directory of Open Access Journals (Sweden)

    Xingtuan Yang

    2014-01-01

    Full Text Available Natural circulation is an important process for primary loops of some marine integrated reactors. The reactor works under inclined conditions when severe accidents happen to the ship. In this paper, to investigate the characteristics of natural circulation, experiments were conducted in a symmetric loop under the inclined angle of 0~45°. A CFD model was also set up to predict the behaviors of the loop beyond the experimental scope. Total circulation flow rate decreases with the increase of inclined angle. Meanwhile one circulation is depressed while the other is enhanced, and accordingly the disparity between the branch circulations arises and increases with the increase of inclined angle. Circulation only takes place in one branch circuit at large inclined angle. Also based on the CFD model, the influences of flow resistance distribution and loop configuration on natural circulation are predicted. The numerical results show that to design the loop with the configuration of big altitude difference and small width, it is favorable to reduce the influence of inclination; however too small loop width will cause severe reduction of circulation ability at large angle inclination.

  16. Radiology of liver circulation

    International Nuclear Information System (INIS)

    Hermine, C.L.

    1985-01-01

    This book proposes that careful evaluation of the arterioportogram is the cornerstone in assessing portal flow obstruction, being the most consistent of all observations including liver histology, portal venous pressure, size and number of portosystemic collaterals, and wedged hepatic venous pressure. Very brief chapters cover normal hepatic circulation and angiographic methods. Contrast volumes and flow rates for celiac, hepatic, and superior mesenteric injection are given, with the timing for venous phase radiographs. In the main body of the text, portal obstruction is divided very simply into presinusoidal (all proximal causes) and postsinusoidal (all distal causes, including Budd-Chiari). Changes are discussed regarding the splenic artery and spleen; hepatic artery and its branches; portal flow rate and direction; and arterioportal shunting and portosystemic collateral circulation in minimal, moderate, severe, and very severe portal obstruction and in recognizable entities such as prehepatic portal and hepatic venous obstructions. The major emphasis in this section is the recognition and understanding of flow changes by which level and severity of obstruction are assessed (not simply the anatomy of portosystemic collateral venous flow). Excellent final chapters discuss the question of portal hypertension without obstruction, and the contribution of arterioportography to the treatment of portal hypertension, again with an emphasis on hemodynamics before and after shunt surgery. There is a fascinating final chapter on segmental intrahepatic obstruction without portal hypertension that explains much of the unusual contrast enhancement sometimes seen in CT scanning of hepatic mass lesions

  17. Anti-cyclonic circulation driven by the estuarine circulation in a gulf type ROFI

    Science.gov (United States)

    Fujiwara, T.; Sanford, L. P.; Nakatsuji, K.; Sugiyama, Y.

    1997-08-01

    Baroclinic residual circulation processes are examined in gulf type Regions Of Freshwater Influence (ROFIs), which have large rivers discharging into a rounded head wider than the Rossby internal deformation radius. Theoretical and observational investigations concentrate on Ise Bay, Japan, with supporting data from Osaka Bay and Tokyo Bay. Simplified analytical solutions are derived to describe the primary features of the circulation. Three dimensional residual current data collected using moored current meters and shipboard acoustic doppler current profilers (ADCPs), satellite imagery and density structure data observed using STDs, are presented for comparison to the theoretical predictions. There are three key points to understanding the resulting circulation in gulf type ROFIs. First, there are likely to be three distinct water masses: the river plume, a brackish upper layer, and a higher salinity lower layer. Second, baroclinic processes in gulf type ROFIs are influenced by the Earth's rotation at first order. Residual currents are quasi-geostrophic and potential vorticity is approximately conserved. Third, the combined effects of a classical longitudinal estuarine circulation and the Earth's rotation are both necessary to produce the resulting circulation. Anti-cyclonic vorticity is generated in the upper layer by the horizontal divergence associated with upward entrainment, which is part of the estuarine circulation. The interaction between anti-cyclonic vorticity and horizontal divergence results in two regions of qualitatively different circulation, with gyre-like circulation near the bay head and uniformly seaward anti-cyclonicly sheared flow further towards the mouth. The stagnation point separating the two regions is closer to (further away from) the bay head for stronger (weaker) horizontal divergence, respectively. The vorticity and spin-up time of this circulation are-(ƒ-ω 1)/2 and h/2w 0, respectively, where ƒ is the Coriolis parameter, ω 1 is

  18. Marine metabolites: The sterols of soft coral

    Digital Repository Service at National Institute of Oceanography (India)

    Sarma, N.S.; Krishna, M.S.; Pasha, Sk.G.; Rao, T.S.P.; Venkateswarlu, Y.; Parameswaran, P.S.

    Sterols constitute a major group of secondary metabolites of soft corals. Several of these compounds have the 'usual' 3 beta-hydroxy, delta sup(5) (or delta sup(0)) cholestane skeleton, a large number of these metabolites are polar sterols...

  19. Circulation Systems Past and Present

    Directory of Open Access Journals (Sweden)

    Maurice J. Freedman

    1981-01-01

    Full Text Available A review of the development of circulation systems shows two areas of change. The librarian's perception of circulation control has shifted from a broad service orientation to a narrow record-keeping approach and recently back again. The technological development of circulation sys-tems has evolved from manual systems to the online systems of today. The trade-offs and deficiencies of earlier systems in relation to the comprehensive services made possible by the online computer are detailed.

  20. The ocean circulation inverse problem

    National Research Council Canada - National Science Library

    Wunsch, C

    1996-01-01

    .... This book addresses the problem of inferring the state of the ocean circulation, understanding it dynamically, and even forecasting it through a quantitative combination of theory and observation...

  1. State of the Art Report for a Bearing for VHTR Helium Circulator

    International Nuclear Information System (INIS)

    Lee, Jae Seon; Song, Kee Nam; Kim, Yong Wan; Lee, Won Jae

    2008-10-01

    A helium circulator in a VHTR(Very High Temperature gas-cooled Reactor) plays a core role which translates thermal energy at high temperature from a nuclear core to a steam generator. Helium as a operating coolant circulates a primary circuit in high temperature and high pressure state, and controls thermal output of a nuclear core by controlling flow rate. A helium circulator is the only rotating machinery in a VHTR, and its reliability should be guaranteed for reliable operation of a reactor and stable production of hydrogen. Generally a main helium circulator is installed on the top of a steam generator vessel, and helium is circulated only by a main helium circulator in a normal operation state. An auxiliary or shutdown circulator is installed at the bottom of a reactor vessel, and it is an auxiliary circulator for shutting down a reactor in case of refueling or accelerating cooling down in case of fast cooling. Since a rotating shaft of a helium circulator is supported by bearings, bearings are the important machine elements which determines reliability of a helium circulator and a nuclear reactor. Various types of support bearings have been developed and applied for circulator bearings since 1960s, and it is still developing for developing VHTRs. So it is necessary to review and analyze the current technical state of helium circulator support bearings to develop bearings for Koran developing VHTR helium circulator

  2. Metabolites from inhalation of aerosolized S-8 synthetic jet fuel in rats.

    Science.gov (United States)

    Tremblay, Raphael T; Martin, Sheppard A; Fisher, Jeffrey W

    2011-01-01

    Alternative fuels are being considered for civilian and military uses. One of these is S-8, a replacement jet fuel synthesized using the Fischer-Tropsch process, which contains no aromatic compounds and is mainly composed of straight and branched alkanes. Metabolites of S-8 fuel in laboratory animals have not been identified. The goal of this study was to identify metabolic products from exposure to aerosolized S-8 and a designed straight-chain alkane/polyaromatic mixture (decane, undecane, dodecane, tridecane, tetradecane, pentadecane, naphthalene, and 2-methylnaphthalene) in male Fischer 344 rats. Collected blood and tissue samples were analyzed for 70 straight and branched alcohols and ketones ranging from 7 to 15 carbons. No fuel metabolites were observed in the blood, lungs, brain, and fat following S-8 exposure. Metabolites were detected in the liver, urine, and feces. Most of the metabolites were 2- and 3-position alcohols and ketones of prominent hydrocarbons with very few 1- or 4-position metabolites. Following exposure to the alkane mixture, metabolites were observed in the blood, liver, and lungs. Interestingly, heavy metabolites (3-tridecanone, 2-tridecanol, and 2-tetradecanol) were observed only in the lung tissues possibly indicating that metabolism occurred in the lungs. With the exception of these heavy metabolites, the metabolic profiles observed in this study are consistent with previous studies reporting on the metabolism of individual alkanes. Further work is needed to determine the potential metabolic interactions of parent, primary, and secondary metabolites and identify more polar metabolites. Some metabolites may have potential use as biomarkers of exposure to fuels.

  3. Race and sex differences in small-molecule metabolites and metabolic hormones in overweight and obese adults.

    Science.gov (United States)

    Patel, Mahesh J; Batch, Bryan C; Svetkey, Laura P; Bain, James R; Turer, Christy Boling; Haynes, Carol; Muehlbauer, Michael J; Stevens, Robert D; Newgard, Christopher B; Shah, Svati H

    2013-12-01

    In overweight/obese individuals, cardiometabolic risk factors differ by race and sex categories. Small-molecule metabolites and metabolic hormone levels might also differ across these categories and contribute to risk factor heterogeneity. To explore this possibility, we performed a cross-sectional analysis of fasting plasma levels of 69 small-molecule metabolites and 13 metabolic hormones in 500 overweight/obese adults who participated in the Weight Loss Maintenance trial. Principal-components analysis (PCA) was used for reduction of metabolite data. Race and sex-stratified comparisons of metabolite factors and metabolic hormones were performed. African Americans represented 37.4% of the study participants, and females 63.0%. Of thirteen metabolite factors identified, three differed by race and sex: levels of factor 3 (branched-chain amino acids and related metabolites, phormones regulating body weight homeostasis. Among overweight/obese adults, there are significant race and sex differences in small-molecule metabolites and metabolic hormones; these differences may contribute to risk factor heterogeneity across race and sex subgroups and should be considered in future investigations with circulating metabolites and metabolic hormones.

  4. Correlative analysis of metabolite profiling of Danggui Buxue Tang in rat biological fluids by rapid resolution LC-TOF/MS.

    Science.gov (United States)

    Li, Chang-Yin; Qi, Lian-Wen; Li, Ping

    2011-04-28

    In this work, the metabolite profiles of Danggui Buxue Tang (DBT) in rat bile and plasma were qualitatively described, and the possible metabolic pathways of DBT were subsequently proposed. Emphasis was put on correlative analysis of metabolite profiling in different biological fluids. After oral administration of DBT, bile and plasma samples were collected and pretreated by solid phase extraction. Rapid resolution liquid chromatography coupled to time-of-flight mass spectrometry (RRLC-TOFMS) was used for characterization of DBT-related compounds (parent compounds and metabolites) in biological matrices. A total of 142 metabolites were detected and tentatively identified from the drug-containing bile and plasma samples. Metabolite profiling shows that rat bile contained relatively more glutathione-derived conjugates, more saponins compounds and more diverse forms of metabolites than urine. The metabolite profile in plasma revealed that glucuronide conjugates of isoflavonoids, dimmers, acetylcysteine conjugates and parent form of phthalides, as well as saponin aglycones were the major circulating forms of DBT. Collectively, the metabolite profile analysis of DBT in different biological matrices provided a comprehensive understanding of the in vivo metabolic fates of constituents in DBT. Copyright © 2011 Elsevier B.V. All rights reserved.

  5. Metabolite Profiles of Diabetes Risk

    OpenAIRE

    Gerszten, Robert E.

    2013-01-01

    Metabolic diseases present particular difficulty for clinicians because they are often present for years before becoming clinically apparent. We investigated whether metabolite profiles can predict the development of diabetes in the Framingham Heart Study. Five branched-chain and aromatic amino acids had highly-significant associations with future diabetes, while a combination of three amino acids strongly predicted future diabetes by up to 12 years (>5-fold increased risk for individuals in ...

  6. Prediction of Relative In Vivo Metabolite Exposure from In Vitro Data Using Two Model Drugs: Dextromethorphan and Omeprazole

    Science.gov (United States)

    Lutz, Justin D.

    2012-01-01

    Metabolites can have pharmacological or toxicological effects, inhibit metabolic enzymes, and be used as probes of drug-drug interactions or specific cytochrome P450 (P450) phenotypes. Thus, better understanding and prediction methods are needed to characterize metabolite exposures in vivo. This study aimed to test whether in vitro data could be used to predict and rationalize in vivo metabolite exposures using two model drugs and P450 probes: dextromethorphan and omeprazole with their primary metabolites dextrorphan, 5-hydroxyomeprazole (5OH-omeprazole), and omeprazole sulfone. Relative metabolite exposures were predicted using metabolite formation and elimination clearances. For dextrorphan, the formation clearances of dextrorphan glucuronide and 3-hydroxymorphinan from dextrorphan in human liver microsomes were used to predict metabolite (dextrorphan) clearance. For 5OH-omeprazole and omeprazole sulfone, the depletion rates of the metabolites in human hepatocytes were used to predict metabolite clearance. Dextrorphan/dextromethorphan in vivo metabolite/parent area under the plasma concentration versus time curve ratio (AUCm/AUCp) was overpredicted by 2.1-fold, whereas 5OH-omeprazole/omeprazole and omeprazole sulfone/omeprazole were predicted within 0.75- and 1.1-fold, respectively. The effect of inhibition or induction of the metabolite's formation and elimination on the AUCm/AUCp ratio was simulated. The simulations showed that unless metabolite clearance pathways are characterized, interpretation of the metabolic ratios is exceedingly difficult. This study shows that relative in vivo metabolite exposure can be predicted from in vitro data and characterization of secondary metabolism of probe metabolites is critical for interpretation of phenotypic data. PMID:22010218

  7. Metabolites in vertebrate Hedgehog signaling.

    Science.gov (United States)

    Roberg-Larsen, Hanne; Strand, Martin Frank; Krauss, Stefan; Wilson, Steven Ray

    2014-04-11

    The Hedgehog (HH) signaling pathway is critical in embryonic development, stem cell biology, tissue homeostasis, chemoattraction and synapse formation. Irregular HH signaling is associated with a number of disease conditions including congenital disorders and cancer. In particular, deregulation of HH signaling has been linked to skin, brain, lung, colon and pancreatic cancers. Key mediators of the HH signaling pathway are the 12-pass membrane protein Patched (PTC), the 7-pass membrane protein Smoothened (SMO) and the GLI transcription factors. PTC shares homology with the RND family of small-molecule transporters and it has been proposed that it interferes with SMO through metabolites. Although a conclusive picture is lacking, substantial efforts are made to identify and understand natural metabolites/sterols, including cholesterol, vitamin D3, oxysterols and glucocorticoides, that may be affected by, or influence the HH signaling cascade at the level of PTC and SMO. In this review we will elaborate the role of metabolites in HH signaling with a focus on oxysterols, and discuss advancements in modern analytical approaches in the field. Copyright © 2014 Elsevier Inc. All rights reserved.

  8. Analysis of blood clearance and labeled metabolites for the estrogen receptor tracer [F-18]-16α-fluorestradiol (FES)

    International Nuclear Information System (INIS)

    Mankoff, David A.; Tewson, Timothy J.; Eary, Janet F.

    1997-01-01

    [F-18] 16α-Fluoroestradiol (FES) has been shown to be a tracer of estrogen receptor content in breast tumors; however, quantitative analysis of FES images is complicated by the rapid metabolism of the tracer in vivo. To optimize FES PET imaging studies and to provide an input function for the quantitative analysis of the tracer FES uptake in breast tumors, we studied the clearance and metabolism of FES in 15 breast cancer patients. FES clearance, protein binding, and metabolite production and limited assays to determine the identity of labeled metabolites were performed. These studies show that FES was rapidly cleared from the blood and metabolized; at 20 min only 20% of the circulating radioactivity was unmetabolized FES, and much of this was protein bound. The detectable metabolites in either blood or urine are conjugation products, largely the glucuronide and the sulfate of FES, and these are excreted through the kidneys at a rate comparable to their introduction into the circulation. After 20 min postinjection the blood levels of radioactivity remain fairly constant. Our results, the first report on human metabolites, are in close agreement with previous animal studies of FES metabolism. These studies show that because FES clearance is rapid and metabolite background is nearly constant, imaging starting at 20 to 30 min after injection may provide good visualization of estrogen-containing tissues. Labeled metabolites need to be accounted for in quantifying FES uptake

  9. Extraction and metabolism of circulating catecholamines by the trout gill

    International Nuclear Information System (INIS)

    Nekvasil, N.P.; Olson, K.R.

    1986-01-01

    Extraction and metabolism of [3H]-norepinephrine (NE) and [3H]epinephrine (E) by the respiratory (efferent branchial) and filamental (venous) vasculature of the trout gill were examined using an isolated perfused arch technique in which outflow from the two circulations was separated. Deaminated and O-methylated metabolites in the effluent were identified by ion-exchange chromatography. Metabolism by tissue homogenates was also measured. Gill homogenates deaminate catecholamines (CAs) faster than homogenates of liver, kidney, and skeletal muscle; branchial O-methylation was comparable to that of liver and kidney. The perfused gill extracted 60% of a NE pulse and 47% of an E pulse. During continuous CA perfusion the gill removed greater than 30% of the NE from the circulation through extraction and metabolism; only 7% of the E was removed. The gill venous system extracts and metabolizes more CAs than the efferent. NE is the preferred substrate for extraction and metabolism. A mechanism is proposed whereby high circulating CA levels, common during stress, are maintained through CA-induced reduction in venous blood flow. After the stress is alleviated, CA levels begin to fall, flow to the venous pathway increases, and the rate of inactivation of circulating CAs increases

  10. Sino-Danish Brain Circulation

    DEFF Research Database (Denmark)

    Bertelsen, Rasmus Gjedssø; Du, Xiangyun; Søndergaard, Morten Karnøe

    2014-01-01

    China is faced with urgent needs to develop an economically and environmentally sustainable economy based on innovation and knowledge. Brain circulation and research and business investments from the outside are central for this development. Sino-American brain circulation and research...... and investment by overseas researchers and entrepreneurs are well described. In that case, the US is the center of global R&D and S&T. However, the brain circulation and research and investments between a small open Scandinavian economy, such as Denmark, and the huge developing economy of China are not well...... understood. In this case, Denmark is very highly developed, but a satellite in the global R&D and S&T system. With time and the growth of China as a R&D and S&T power house, both Denmark and China will benefit from brain circulation between them. Such brain circulation is likely to play a key role in flows...

  11. Dichlorodiphenyltrichloroethane (DDT), DDT Metabolites and Pregnancy Outcomes

    Science.gov (United States)

    Kezios, Katrina L.; Liu, Xinhua; Cirillo, Piera M.; Cohn, Barbara A.; Kalantzi, Olga I.; Wang, Yunzhu; Petreas, Myrto X.; Park, June-Soo; Factor-Litvak, Pam

    2012-01-01

    Organochlorine pesticides (OCPs) are persistent endocrine disruptors. OCPs cross the placenta; this prenatal exposure has been associated with adverse pregnancy outcomes. We investigated associations between prenatal exposure to OCPs and gestational age and birth weight in 600 infants born between 1960 and 1963. The primary OCP was 1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane (p,p′-DDT), its primary metabolite, 1,1′-dichloro-2,2'-bis(p-chlorophenyl)ethylene(p,p′-DDE) and the contaminant, 1,1,1-trichloro-2-(p-chlorophenyl)-2-(o-chlorophenyl)-ethane (o,p′-DDT). Regression analysis indicated that for each natural log unit increase in p,p′-DDT, birth weight increased by 274 grams (95% CI 122, 425) when controlling for p,p′-DDE and o,p′-DDT. At a given level of p,p′-DDT exposure, o,p′-DDT and p,p′-DDE were associated with decreased birth weight. p,p′-DDE was negatively associated with length of gestation, controlling for p,p′-DDT and o,p′-DDT. These findings suggest opposing associations between exposure to p,p′-DDT and p,p′-DDE and birth weight. We did not find evidence to support mediation by maternal thyroid hormone status nor that the association differed by sex. PMID:23142753

  12. The Role of Drug Metabolites in the Inhibition of Cytochrome P450 Enzymes.

    Science.gov (United States)

    Mikov, Momir; Đanić, Maja; Pavlović, Nebojša; Stanimirov, Bojan; Goločorbin-Kon, Svetlana; Stankov, Karmen; Al-Salami, Hani

    2017-12-01

    Following the drug administration, patients are exposed not only to the parent drug itself, but also to the metabolites generated by drug-metabolizing enzymes. The role of drug metabolites in cytochrome P450 (CYP) inhibition and subsequent drug-drug interactions (DDIs) have recently become a topic of considerable interest and scientific debate. The list of metabolites that were found to significantly contribute to clinically relevant DDIs is constantly being expanded and reported in the literature. New strategies have been developed for better understanding how different metabolites of a drug candidate contribute to its pharmacokinetic properties and pharmacological as well as its toxicological effects. However, the testing of the role of metabolites in CYP inhibition is still not routinely performed during the process of drug development, although the evaluation of time-dependent CYP inhibition during the clinical candidate selection process may provide information on possible effects of metabolites in CYP inhibition. Due to large number of compounds to be tested in the early stages of drug discovery, the experimental approaches for assessment of CYP-mediated metabolic profiles are particularly resource demanding. Consequently, a large number of in silico or computational tools have been developed as useful complement to experimental approaches. In summary, circulating metabolites may be recognized as significant CYP inhibitors. Current data may suggest the need for an optimized effort to characterize the inhibitory potential of parent drugs metabolites on CYP, as well as the necessity to develop the advanced in vitro models that would allow a better quantitative predictive value of in vivo studies.

  13. Natural Circulation with Boiling

    Energy Technology Data Exchange (ETDEWEB)

    Mathisen, R P

    1967-09-15

    A number of parameters with dominant influence on the power level at hydrodynamic instability in natural circulation, two-phase flow, have been studied experimentally. The geometrical dependent quantities were: the system driving head, the boiling channel and riser dimensions, the single-phase as well as the two phase flow restrictions. The parameters influencing the liquid properties were the system pressure and the test section inlet subcooling. The threshold of instability was determined by plotting the noise characteristics in the mass flow records against power. The flow responses to artificially obtained power disturbances at instability conditions were also measured in order to study the nature of hydrodynamic instability. The results presented give a review over relatively wide ranges of the main parameters, mainly concerning the coolant performance in both single and parallel boiling channel flow. With regard to the power limits the experimental results verified that the single boiling channel performance was intimately related to that of the parallel channels. In the latter case the additional inter-channel factors with attenuating effects were studied. Some optimum values of the parameters were observed.

  14. When Prostate Cancer Circulates in the Bloodstream

    Directory of Open Access Journals (Sweden)

    Virginie Vlaeminck-Guillem

    2015-10-01

    Full Text Available Management of patients with prostate cancer is currently based on imperfect clinical, biological, radiological and pathological evaluation. Prostate cancer aggressiveness, including metastatic potential, remains difficult to accurately estimate. In an attempt to better adapt therapeutics to an individual (personalized medicine, reliable evaluation of the intrinsic molecular biology of the tumor is warranted, and particularly for all tumor sites (primary tumors and secondary sites at any time of the disease progression. As a consequence of their natural tendency to grow (passive invasion or as a consequence of an active blood vessel invasion by metastase-initiating cells, tumors shed various materials into the bloodstream. Major efforts have been recently made to develop powerful and accurate methods able to detect, quantify and/or analyze all these circulating tumor materials: circulating tumors cells, disseminating tumor cells, extracellular vesicles (including exosomes, nucleic acids, etc. The aim of this review is to summarize current knowledge about these circulating tumor materials and their applications in translational research.

  15. Urinary excretion of androgen metabolites, comparison with excretion of radioactive metabolites after injection of (4-/sup 14/C)testosterone. Influence of age

    Energy Technology Data Exchange (ETDEWEB)

    Deslypere, J P; Sayed, A; Vermeulen, A [Department of Internal Medicine, Section of Endocrinology, State University Academic Hospital, De Pintelaan, 135, Ghent, Belgium; Wiers, P W [Department of Internal Medicine, Section of Pneumology, State University Academic Hospital, The Netherlands

    1981-01-01

    The influence of age on the metabolic pattern of (4-/sup 14/C)testosterone was studied in 20 young and 8 elderly males and compared to the metabolic pattern of endogenous androgens; the latter was also studied in 16 young and 8 elderly women. In both young and elderly males, androsterone and aetiocholanolone glucuronide represent 65% of (4-/sup 14/C)testosterone metabolites: together with their suephoconjugates as well as with 5..cap alpha..- and 5..beta..-androstane-3..cap alpha.., 17..beta..-diol they represent even more than 75% of total urinary metabolites. The 5..cap alpha../5..beta.. ratio of metabolites of (4-/sup 14/C)testosterone was significantly (P<0.01) correlated with the 5..cap alpha../5..beta.. ratio of the metabolites of the endogenous androgens, mainly dehydroepiandrosterone and androstenedione. The 5..cap alpha../5..beta.. ratio of (4-/sup 14/C)testosterone metabolites was generally higher than the ratio of metabolites of endogenous androgens, suggesting that the transformation of T to ring A saturated metabolites occurs at least partially in another compartment than the transformation of DHEA to these metabolites. For both (4-/sup 14/C)testosterone and endogenous androgen metabolites we observed a statistically significant reduction of the 5..cap alpha../5..beta.. ratio with age, a general phenomenon in both males and females. This reduction concern also 11-OH-androst-4-ene-3.17-dione metabolism. Neither sex hormone levels, nor specific binding seems to determine this age dependent shift; neither is there convincing evidence for latent hypothyroisism or liver dysfunction in the elderly. An age associated primary decrease of the 5..cap alpha..-reductase activity seems the most likely explanation.

  16. Physical activity, sedentary behavior, and vitamin D metabolites.

    Science.gov (United States)

    Hibler, Elizabeth A; Sardo Molmenti, Christine L; Dai, Qi; Kohler, Lindsay N; Warren Anderson, Shaneda; Jurutka, Peter W; Jacobs, Elizabeth T

    2016-02-01

    Physical activity is associated with circulating 25-hydroxyvitamin D (25(OH)D). However, the influence of activity and/or sedentary behavior on the biologically active, seco-steroid hormone 1α,25-dihydroxyvitamin D (1,25(OH)2D) is unknown. We conducted a cross-sectional analysis among ursodeoxycholic acid (UDCA) randomized trial participants (n=876) to evaluate associations between physical activity, sedentary behavior, and circulating vitamin D metabolite concentrations. Continuous vitamin D metabolite measurements and clinical thresholds were evaluated using multiple linear and logistic regression models, mutually adjusted for either 1,25(OH)2D or 25(OH)D and additional confounding factors. A statistically significant linear association between 1,25(OH)2D and moderate-vigorous physical activity per week was strongest among women (β (95% CI): 3.10 (1.51-6.35)) versus men (β (95% CI): 1.35 (0.79-2.29)) in the highest tertile of activity compared to the lowest (p-interaction=0.003). Furthermore, 25(OH)D was 1.54ng/ml (95% CI 1.09-1.98) higher per hour increase in moderate-vigorous activity (p=0.001) and odds of sufficient 25(OH)D status was higher among physically active participants (p=0.001). Sedentary behavior was not significantly associated with either metabolite in linear regression models, nor was a statistically significant interaction by sex identified. The current study identified novel associations between physical activity and serum 1,25(OH)2D levels, adjusted for 25(OH)D concentrations. These results identify the biologically active form of vitamin D as a potential physiologic mechanism related to observed population-level associations between moderate-vigorous physical activity with bone health and chronic disease risk. However, future longitudinal studies are needed to further evaluate the role of physical activity and vitamin D metabolites in chronic disease prevention. Copyright © 2015 Elsevier Inc. All rights reserved.

  17. Engineering Microbial Metabolite Dynamics and Heterogeneity.

    Science.gov (United States)

    Schmitz, Alexander C; Hartline, Christopher J; Zhang, Fuzhong

    2017-10-01

    As yields for biological chemical production in microorganisms approach their theoretical maximum, metabolic engineering requires new tools, and approaches for improvements beyond what traditional strategies can achieve. Engineering metabolite dynamics and metabolite heterogeneity is necessary to achieve further improvements in product titers, productivities, and yields. Metabolite dynamics, the ensemble change in metabolite concentration over time, arise from the need for microbes to adapt their metabolism in response to the extracellular environment and are important for controlling growth and productivity in industrial fermentations. Metabolite heterogeneity, the cell-to-cell variation in a metabolite concentration in an isoclonal population, has a significant impact on ensemble productivity. Recent advances in single cell analysis enable a more complete understanding of the processes driving metabolite heterogeneity and reveal metabolic engineering targets. The authors present an overview of the mechanistic origins of metabolite dynamics and heterogeneity, why they are important, their potential effects in chemical production processes, and tools and strategies for engineering metabolite dynamics and heterogeneity. The authors emphasize that the ability to control metabolite dynamics and heterogeneity will bring new avenues of engineering to increase productivity of microbial strains. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  18. Epigenome targeting by probiotic metabolites

    Directory of Open Access Journals (Sweden)

    Licciardi Paul V

    2010-12-01

    Full Text Available Abstract Background The intestinal microbiota plays an important role in immune development and homeostasis. A disturbed microbiota during early infancy is associated with an increased risk of developing inflammatory and allergic diseases later in life. The mechanisms underlying these effects are poorly understood but are likely to involve alterations in microbial production of fermentation-derived metabolites, which have potent immune modulating properties and are required for maintenance of healthy mucosal immune responses. Probiotics are beneficial bacteria that have the capacity to alter the composition of bacterial species in the intestine that can in turn influence the production of fermentation-derived metabolites. Principal among these metabolites are the short-chain fatty acids butyrate and acetate that have potent anti-inflammatory activities important in regulating immune function at the intestinal mucosal surface. Therefore strategies aimed at restoring the microbiota profile may be effective in the prevention or treatment of allergic and inflammatory diseases. Presentation of the hypothesis Probiotic bacteria have diverse effects including altering microbiota composition, regulating epithelial cell barrier function and modulating of immune responses. The precise molecular mechanisms mediating these probiotic effects are not well understood. Short-chain fatty acids such as butyrate are a class of histone deacetylase inhibitors important in the epigenetic control of host cell responses. It is hypothesized that the biological function of probiotics may be a result of epigenetic modifications that may explain the wide range of effects observed. Studies delineating the effects of probiotics on short-chain fatty acid production and the epigenetic actions of short-chain fatty acids will assist in understanding the association between microbiota and allergic or autoimmune disorders. Testing the hypothesis We propose that treatment with

  19. Bioactive metabolite production by Streptomyces albolongus in favourable environment

    Directory of Open Access Journals (Sweden)

    Myn Uddin

    2013-06-01

    Full Text Available Objectives: Demand for new antibiotic is rising up due to continuous resistance risk against conventional antibiotic.This attempt was taken to find out a novel antimicrobial metabolite.Methods: Chili field antagonistic actinomycetes Streptomyces albolongus was isolated and tested for optimum antimicrobialmetabolite production. Primary screening was done by selective media and antibiotic assay was done by agarcup plate method. Fermented product was recovered by separating funnel using suitable solvent.Results: Maximum antimicrobial metabolite production was found at temperature 35°C and pH 9.0 and on 6th day ofincubation. The medium consisting of corn steep liquor (0.2%, glucose (1.0%, NaCl (0.5%, K2HPO4 (0.1% was screenedout as suitable medium for maximum antimicrobial production. Sucrose was found as the best carbon source amongfour sources. The antimicrobial metabolite was found to be stable at pH and temperature up to 11.0 and 100°C respectively.The active agent was best extracted with chloroform. The antimicrobial spectrum of the metabolite was wideand shows activity against Shigella dysenteriae (AE14612, Shigella sonnei (CRL, ICDDR, B, Salmonella typhi (AE14296,Vibrio cholerae (AE14748, Pseudomonas aeruginosa (CRL, ICDDR, B, Bacillus cereus (BTCC19, Staphylococcus aureus(ATCC6538, Bacillus subtilis (BTTC17 and Bacillus megaterium (BTTC18.Conclusions: The findings of antibacterial activity of S. albolongus against several species of human pathogens includingboth Gram-positive and Gram-negative bacteria indicated that our produced material might be an alternative antimicrobialsubstance to control human diseases. J Microbiol Infect Dis 2013; 3(2: 75-82Key words: Streptomyces albolongus, antimicrobial metabolite, optimum production, antimicrobial spectrum

  20. Coolant rate distribution in horizontal steam generator under natural circulation

    International Nuclear Information System (INIS)

    Blagovechtchenski, A.; Leontieva, V.; Mitrioukhin, A.

    1997-01-01

    In the presentation the major factors determining the conditions of NCC (Natural Coolant Circulation) in the primary circuit and in particular conditions of coolant rate distribution on the horizontal tubes of PGV-1000 in NPP with VVER-1000 under NCC are considered

  1. Coolant rate distribution in horizontal steam generator under natural circulation

    Energy Technology Data Exchange (ETDEWEB)

    Blagovechtchenski, A.; Leontieva, V.; Mitrioukhin, A. [St. Petersburg State Technical Univ. (Russian Federation)

    1997-12-31

    In the presentation the major factors determining the conditions of NCC (Natural Coolant Circulation) in the primary circuit and in particular conditions of coolant rate distribution on the horizontal tubes of PGV-1000 in NPP with VVER-1000 under NCC are considered. 5 refs.

  2. Coolant rate distribution in horizontal steam generator under natural circulation

    Energy Technology Data Exchange (ETDEWEB)

    Blagovechtchenski, A; Leontieva, V; Mitrioukhin, A [St. Petersburg State Technical Univ. (Russian Federation)

    1998-12-31

    In the presentation the major factors determining the conditions of NCC (Natural Coolant Circulation) in the primary circuit and in particular conditions of coolant rate distribution on the horizontal tubes of PGV-1000 in NPP with VVER-1000 under NCC are considered. 5 refs.

  3. Seasonal overturning circulation in the Red Sea: 2. Winter circulation

    Science.gov (United States)

    Yao, Fengchao; Hoteit, Ibrahim; Pratt, Larry J.; Bower, Amy S.; Köhl, Armin; Gopalakrishnan, Ganesh; Rivas, David

    2014-04-01

    The shallow winter overturning circulation in the Red Sea is studied using a 50 year high-resolution MITgcm (MIT general circulation model) simulation with realistic atmospheric forcing. The overturning circulation for a typical year, represented by 1980, and the climatological mean are analyzed using model output to delineate the three-dimensional structure and to investigate the underlying dynamical mechanisms. The horizontal model circulation in the winter of 1980 is dominated by energetic eddies. The climatological model mean results suggest that the surface inflow intensifies in a western boundary current in the southern Red Sea that switches to an eastern boundary current north of 24°N. The overturning is accomplished through a cyclonic recirculation and a cross-basin overturning circulation in the northern Red Sea, with major sinking occurring along a narrow band of width about 20 km along the eastern boundary and weaker upwelling along the western boundary. The northward pressure gradient force, strong vertical mixing, and horizontal mixing near the boundary are the essential dynamical components in the model's winter overturning circulation. The simulated water exchange is not hydraulically controlled in the Strait of Bab el Mandeb; instead, the exchange is limited by bottom and lateral boundary friction and, to a lesser extent, by interfacial friction due to the vertical viscosity at the interface between the inflow and the outflow.

  4. Circulating vitamin D binding protein levels are not associated with relapses or with vitamin D status in multiple sclerosis

    NARCIS (Netherlands)

    Smolders, J; Peelen, Evelyn; Thewissen, Mariëlle; Menheere, Paul; Damoiseaux, Jan; Hupperts, Raymond

    BACKGROUND: A low vitamin D status has been associated with multiple sclerosis (MS). Most circulating vitamin D metabolites are bound to vitamin D binding protein (DBP). OBJECTIVES: The purpose of this study was to explore whether there is an association between MS and DBP. METHODS: We compared DBP

  5. of Several Organophosphorus Insecticide Metabolites

    Directory of Open Access Journals (Sweden)

    Russell L. Carr

    2015-01-01

    Full Text Available Paraoxonase (PON1 is a calcium dependent enzyme that is capable of hydrolyzing organophosphate anticholinesterases. PON1 activity is present in most mammals and previous research established that PON1 activity differs depending on the species. These studies mainly used the organophosphate substrate paraoxon, the active metabolite of the insecticide parathion. Using serum PON1 from different mammalian species, we compared the hydrolysis of paraoxon with the hydrolysis of the active metabolites (oxons of two additional organophosphorus insecticides, methyl parathion and chlorpyrifos. Paraoxon hydrolysis was greater than that of methyl paraoxon, but the level of activity between species displayed a similar pattern. Regardless of the species tested, the hydrolysis of chlorpyrifos-oxon was significantly greater than that of paraoxon or methyl paraoxon. These data indicate that chlorpyrifos-oxon is a better substrate for PON1 regardless of the species. The pattern of species differences in PON1 activity varied with the change in substrate to chlorpyrifos-oxon from paraoxon or methyl paraoxon. For example, the sex difference observed here and reported elsewhere in the literature for rat PON1 hydrolysis of paraoxon was not present when chlorpyrifos-oxon was the substrate.

  6. Application of dried blood spot cards to determine olive oil phenols (hydroxytyrosol metabolites) in human blood.

    Science.gov (United States)

    de Las Hazas, María Carmen López; Motilva, Maria José; Piñol, Carme; Macià, Alba

    2016-10-01

    In this study, a fast and simple blood sampling and sample pre-treatment method based on the use of the dried blood spot (DBS) cards and ultra-performance liquid chromatography coupled to tandem mass spectrometry (UPLC-MS/MS) for the quantification of olive oil phenolic metabolites in human blood was developed and validated. After validation, the method was applied to determine hydroxytyrosol metabolites in human blood samples after the acute intake of an olive oil phenolic extract. Using the FTA DMPK-A DBS card under optimum conditions, with 20µL as the blood solution volume, 100µL of methanol/Milli-Q water (50/50, v/v) as the extraction solvent and 7 disks punched out from the card, the main hydroxytyrosol metabolites (hydroxytyrosol-3-O-sulphate and hydroxytyrosol acetate sulphate) were identified and quantified. The developed methodology allowed detecting and quantifying the generated metabolites at low μM levels. The proposed method is a significant improvement over existing methods to determine phenolic metabolites circulating in blood and plasma samples, thus making blood sampling possible with the volunteer pricking their own finger, and the subsequent storage of the blood in the DBS cards prior to chromatographic analysis. Copyright © 2016 Elsevier B.V. All rights reserved.

  7. Metabolic Profiling and Antioxidant Assay of Metabolites from Three Radish Cultivars (Raphanus sativus

    Directory of Open Access Journals (Sweden)

    Chang Ha Park

    2016-01-01

    Full Text Available A total of 13 anthocyanins and 33 metabolites; including organic acids, phenolic acids, amino acids, organic compounds, sugar acids, sugar alcohols, and sugars, were profiled in three radish cultivars by using high-performance liquid chromatography (HPLC and gas chromatography time-of-flight mass spectrometry (GC-TOFMS-based metabolite profiling. Total phenolics and flavonoids and their in vitro antioxidant activities were assessed. Pelargonidins were found to be the major anthocyanin in the cultivars studied. The cultivar Man Tang Hong showed the highest level of anthocyanins (1.89 ± 0.07 mg/g, phenolics (0.0664 ± 0.0033 mg/g and flavonoids (0.0096 ± 0.0004 mg/g. Here; the variation of secondary metabolites in the radishes is described, as well as their association with primary metabolites. The low-molecular-weight hydrophilic metabolite profiles were subjected to principal component analysis (PCA, hierarchical clustering analysis (HCA, Pearson’s correlation analysis. PCA fully distinguished the three radish cultivars tested. The polar metabolites were strongly correlated between metabolites that participate in the TCA cycle. The chemometrics results revealed that TCA cycle intermediates and free phenolic acids as well as anthocyanins were higher in the cultivar Man Tang Hong than in the others. Furthermore; superoxide radical scavenging activities and 1,1-diphenyl-2-picrylhydrazyl (DPPH radical scavenging were investigated to elucidate the antioxidant activity of secondary metabolites in the cultivars. Man Tang Hong showed the highest superoxide radical scavenging activity (68.87% at 1000 μg/mL, and DPPH activity (20.78%, followed by Seo Ho and then Hong Feng No. 1. The results demonstrate that GC-TOFMS-based metabolite profiling, integrated with chemometrics, is an applicable method for distinguishing phenotypic variation and determining biochemical reactions connecting primary and secondary metabolism. Therefore; this study might

  8. Correcting ligands, metabolites, and pathways

    Directory of Open Access Journals (Sweden)

    Vriend Gert

    2006-11-01

    Full Text Available Abstract Background A wide range of research areas in bioinformatics, molecular biology and medicinal chemistry require precise chemical structure information about molecules and reactions, e.g. drug design, ligand docking, metabolic network reconstruction, and systems biology. Most available databases, however, treat chemical structures more as illustrations than as a datafield in its own right. Lack of chemical accuracy impedes progress in the areas mentioned above. We present a database of metabolites called BioMeta that augments the existing pathway databases by explicitly assessing the validity, correctness, and completeness of chemical structure and reaction information. Description The main bulk of the data in BioMeta were obtained from the KEGG Ligand database. We developed a tool for chemical structure validation which assesses the chemical validity and stereochemical completeness of a molecule description. The validation tool was used to examine the compounds in BioMeta, showing that a relatively small number of compounds had an incorrect constitution (connectivity only, not considering stereochemistry and that a considerable number (about one third had incomplete or even incorrect stereochemistry. We made a large effort to correct the errors and to complete the structural descriptions. A total of 1468 structures were corrected and/or completed. We also established the reaction balance of the reactions in BioMeta and corrected 55% of the unbalanced (stoichiometrically incorrect reactions in an automatic procedure. The BioMeta database was implemented in PostgreSQL and provided with a web-based interface. Conclusion We demonstrate that the validation of metabolite structures and reactions is a feasible and worthwhile undertaking, and that the validation results can be used to trigger corrections and improvements to BioMeta, our metabolite database. BioMeta provides some tools for rational drug design, reaction searches, and

  9. Glutamine and glutamate as vital metabolites

    Directory of Open Access Journals (Sweden)

    Newsholme P.

    2003-01-01

    Full Text Available Glucose is widely accepted as the primary nutrient for the maintenance and promotion of cell function. This metabolite leads to production of ATP, NADPH and precursors for the synthesis of macromolecules such as nucleic acids and phospholipids. We propose that, in addition to glucose, the 5-carbon amino acids glutamine and glutamate should be considered to be equally important for maintenance and promotion of cell function. The functions of glutamine/glutamate are many, i.e., they are substrates for protein synthesis, anabolic precursors for muscle growth, they regulate acid-base balance in the kidney, they are substrates for ureagenesis in the liver and for hepatic and renal gluconeogenesis, they act as an oxidative fuel for the intestine and cells of the immune system, provide inter-organ nitrogen transport, and act as precursors of neurotransmitter synthesis, of nucleotide and nucleic acid synthesis and of glutathione production. Many of these functions are interrelated with glucose metabolism. The specialized aspects of glutamine/glutamate metabolism of different glutamine-utilizing cells are discussed in the context of glucose requirements and cell function.

  10. Demonstration of circulating 1,24,25-trihydroxyvitamin D3 in man by radioimmunoassay

    International Nuclear Information System (INIS)

    Clemens, T.L.; Fraher, L.J.; Sandler, L.M.; O'Riordan, J.L.H.

    1982-01-01

    1,24,25-trihydroxyvitamin D 3 has been detected in human serum using a sensitive radioimmunoassay. Tritiated 1,24,25-trihydroxyvitamin D 3 was synthesized biologically and used as tracer to monitor the recovery of endogenous metabolite during isolation from serum. Circulating 1,24,25(OH) 3 D 3 in normal subjects ranged from 9.3 to 18.5 pmol/l but was not detectable ( 3 . (author)

  11. Genetic Variants Associated with Circulating Parathyroid Hormone.

    Science.gov (United States)

    Robinson-Cohen, Cassianne; Lutsey, Pamela L; Kleber, Marcus E; Nielson, Carrie M; Mitchell, Braxton D; Bis, Joshua C; Eny, Karen M; Portas, Laura; Eriksson, Joel; Lorentzon, Mattias; Koller, Daniel L; Milaneschi, Yuri; Teumer, Alexander; Pilz, Stefan; Nethander, Maria; Selvin, Elizabeth; Tang, Weihong; Weng, Lu-Chen; Wong, Hoi Suen; Lai, Dongbing; Peacock, Munro; Hannemann, Anke; Völker, Uwe; Homuth, Georg; Nauk, Matthias; Murgia, Federico; Pattee, Jack W; Orwoll, Eric; Zmuda, Joseph M; Riancho, Jose Antonio; Wolf, Myles; Williams, Frances; Penninx, Brenda; Econs, Michael J; Ryan, Kathleen A; Ohlsson, Claes; Paterson, Andrew D; Psaty, Bruce M; Siscovick, David S; Rotter, Jerome I; Pirastu, Mario; Streeten, Elizabeth; März, Winfried; Fox, Caroline; Coresh, Josef; Wallaschofski, Henri; Pankow, James S; de Boer, Ian H; Kestenbaum, Bryan

    2017-05-01

    Parathyroid hormone (PTH) is a primary calcium regulatory hormone. Elevated serum PTH concentrations in primary and secondary hyperparathyroidism have been associated with bone disease, hypertension, and in some studies, cardiovascular mortality. Genetic causes of variation in circulating PTH concentrations are incompletely understood. We performed a genome-wide association study of serum PTH concentrations among 29,155 participants of European ancestry from 13 cohort studies ( n =22,653 and n =6502 in discovery and replication analyses, respectively). We evaluated the association of single nucleotide polymorphisms (SNPs) with natural log-transformed PTH concentration adjusted for age, sex, season, study site, and principal components of ancestry. We discovered associations of SNPs from five independent regions with serum PTH concentration, including the strongest association with rs6127099 upstream of CYP24A1 ( P =4.2 × 10 -53 ), a gene that encodes the primary catabolic enzyme for 1,25-dihydroxyvitamin D and 25-dihydroxyvitamin D. Each additional copy of the minor allele at this SNP associated with 7% higher serum PTH concentration. The other SNPs associated with serum PTH concentration included rs4074995 within RGS14 ( P =6.6 × 10 -17 ), rs219779 adjacent to CLDN14 ( P =3.5 × 10 -16 ), rs4443100 near RTDR1 ( P =8.7 × 10 -9 ), and rs73186030 near CASR ( P =4.8 × 10 -8 ). Of these five SNPs, rs6127099, rs4074995, and rs219779 replicated. Thus, common genetic variants located near genes involved in vitamin D metabolism and calcium and renal phosphate transport associated with differences in circulating PTH concentrations. Future studies could identify the causal variants at these loci, and the clinical and functional relevance of these variants should be pursued. Copyright © 2017 by the American Society of Nephrology.

  12. Antimycobacterial Metabolites from Marine Invertebrates.

    Science.gov (United States)

    Daletos, Georgios; Ancheeva, Elena; Chaidir, Chaidir; Kalscheuer, Rainer; Proksch, Peter

    2016-10-01

    Marine organisms play an important role in natural product-based drug research due to accumulation of structurally unique and bioactive metabolites. The exploration of marine-derived compounds may significantly extend the scientific knowledge of potential scaffolds for antibiotic drug discovery. Development of novel antitubercular agents is especially significant as the emergence of drug-resistant Mycobacterium tuberculosis strains remains threateningly high. Marine invertebrates (i.e., sponges, corals, gorgonians) as a source of new chemical entities are the center of research for several scientific groups, and the wide spectrum of biological activities of marine-derived compounds encourages scientists to carry out investigations in the field of antibiotic research, including tuberculosis treatment. The present review covers published data on antitubercular natural products from marine invertebrates grouped according to their biogenetic origin. Studies on the structure-activity relationships of these important leads are highlighted as well. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  13. The secondary metabolite bioinformatics portal

    DEFF Research Database (Denmark)

    Weber, Tilmann; Kim, Hyun Uk

    2016-01-01

    . In this context, this review gives a summary of tools and databases that currently are available to mine, identify and characterize natural product biosynthesis pathways and their producers based on ‘omics data. A web portal called Secondary Metabolite Bioinformatics Portal (SMBP at http...... analytical and chemical methods gave access to this group of compounds, nowadays genomics-based methods offer complementary approaches to find, identify and characterize such molecules. This paradigm shift also resulted in a high demand for computational tools to assist researchers in their daily work......Natural products are among the most important sources of lead molecules for drug discovery. With the development of affordable whole-genome sequencing technologies and other ‘omics tools, the field of natural products research is currently undergoing a shift in paradigms. While, for decades, mainly...

  14. Microsomal metabolism of trenbolone acetate metabolites ...

    Science.gov (United States)

    Trenbolone acetate (TBA) is a synthetic growth promoter widely used in animal agriculture, and its metabolites are suspected endocrine disrupting compounds in agriculturally impacted receiving waters. However, beyond the three widely recognized TBA metabolites (17-trenbolone, 17-trenbolone and trendione), little is known about other metabolites formed in vivo and subsequently discharged into the environment, with some evidence suggesting these unknown metabolites comprise a majority of the TBA mass dosed to the animal. Here, we explored the metabolism of the three known TBA metabolites using rat liver microsome studies. All TBA metabolites are transformed into a complex mixture of monohydroxylated products. Based on product characterization, the majority are more polar than the parent metabolites but maintain their characteristic trienone backbone. A minor degree of interconversion between known metabolites was also observed, as were higher order hydroxylated products with a greater extent of reaction. Notably, the distribution and yield of products were generally comparable across a series of variably induced rat liver microsomes, as well as during additional studies with human and bovine liver microsomes. Bioassays conducted with mixtures of these transformation products suggest that androgen receptor (AR) binding activity is diminished as a result of the microsomal treatment, suggesting that the transformation products are generally less potent than

  15. SECONDARY METABOLITES FROM MARINE PENICILLIUM BREVICOMPACTUM

    OpenAIRE

    ROVIROSA, JUANA; DIAZ-MARRERO, ANA; DARIAS, JOSE; PAINEMAL, KARIN; SAN MARTIN, AURELIO

    2006-01-01

    In a screening of Basidiomycete cultures isolated from marine invertebrates collected along the Chilean coastline for the production of antibiotics we identified a Penicillium brevicompactum strain as a producer of metabolites inhibiting the growth of bacteria and fungi. Bioactivity guided purification resulted in the isolation of four known metabolites. Their structures were elucidated by spectroscopic methods.

  16. Biochemical and secondary metabolites changes under moisture ...

    African Journals Online (AJOL)

    The study showed the importance of carbohydrate and nitrogen cycle related metabolites in mediating tolerance in cassava by affecting their phenotypic expression in the plant. Keywords: Hydrothermal stress, bio-chemicals, pigments, secondary metabolites, cassava. African Journal of Biotechnology, Vol 13(31) 3173-3186 ...

  17. MARSI: metabolite analogues for rational strain improvement

    DEFF Research Database (Denmark)

    Cardoso, João G. R.; Zeidan, Ahmad A; Jensen, Kristian

    2018-01-01

    reactions in an organism can be used to predict effects of MAs on cellular phenotypes. Here, we present the Metabolite Analogues for Rational Strain Improvement (MARSI) framework. MARSI provides a rational approach to strain improvement by searching for metabolites as targets instead of genes or reactions...

  18. Seasonal overturning circulation in the Red Sea: 2. Winter circulation

    KAUST Repository

    Yao, Fengchao

    2014-04-01

    The shallow winter overturning circulation in the Red Sea is studied using a 50 year high-resolution MITgcm (MIT general circulation model) simulation with realistic atmospheric forcing. The overturning circulation for a typical year, represented by 1980, and the climatological mean are analyzed using model output to delineate the three-dimensional structure and to investigate the underlying dynamical mechanisms. The horizontal model circulation in the winter of 1980 is dominated by energetic eddies. The climatological model mean results suggest that the surface inflow intensifies in a western boundary current in the southern Red Sea that switches to an eastern boundary current north of 24N. The overturning is accomplished through a cyclonic recirculation and a cross-basin overturning circulation in the northern Red Sea, with major sinking occurring along a narrow band of width about 20 km along the eastern boundary and weaker upwelling along the western boundary. The northward pressure gradient force, strong vertical mixing, and horizontal mixing near the boundary are the essential dynamical components in the model\\'s winter overturning circulation. The simulated water exchange is not hydraulically controlled in the Strait of Bab el Mandeb; instead, the exchange is limited by bottom and lateral boundary friction and, to a lesser extent, by interfacial friction due to the vertical viscosity at the interface between the inflow and the outflow. Key Points Sinking occurs in a narrow boundary layer along the eastern boundary Surface western boundary current switches into an eastern boundary current Water exchange in the Strait of Bab el Mandeb is not hydraulically controlled © 2014. American Geophysical Union. All Rights Reserved.

  19. The Invertibility, Explicit Determinants, and Inverses of Circulant and Left Circulant and g-Circulant Matrices Involving Any Continuous Fibonacci and Lucas Numbers

    Directory of Open Access Journals (Sweden)

    Zhaolin Jiang

    2014-01-01

    Full Text Available Circulant matrices play an important role in solving delay differential equations. In this paper, circulant type matrices including the circulant and left circulant and g-circulant matrices with any continuous Fibonacci and Lucas numbers are considered. Firstly, the invertibility of the circulant matrix is discussed and the explicit determinant and the inverse matrices by constructing the transformation matrices are presented. Furthermore, the invertibility of the left circulant and g-circulant matrices is also studied. We obtain the explicit determinants and the inverse matrices of the left circulant and g-circulant matrices by utilizing the relationship between left circulant, g-circulant matrices and circulant matrix, respectively.

  20. Circulating blood metabolites in early-lactation dairy cows fed canola or soybean meals

    Science.gov (United States)

    A successful transition from pregnancy to lactation is imperative for dairy cows to maximize milk production potential. Altering the dietary protein source can change the availability of energy to the cow. The objective of this experiment was to evaluate the effect of crude protein (CP) source canol...

  1. Ozone Exposure Increases Circulating Stress Hormones and Lipid Metabolites in Humans

    Science.gov (United States)

    RATIONALE: Air pollution has been associated with increased prevalence of type 2 diabetes; however, the mechanisms remain unknown. We have shown that acute ozone exposure in rats induces release of stress hormones, hyperglycemia, leptinemia, and gluoose intolerance that are assoc...

  2. Complicating factors in safety testing of drug metabolites: Kinetic differences between generated and preformed metabolites

    International Nuclear Information System (INIS)

    Prueksaritanont, Thomayant; Lin, Jiunn H.; Baillie, Thomas A.

    2006-01-01

    This paper aims to provide a scientifically based perspective on issues surrounding the proposed toxicology testing of synthetic drug metabolites as a means of ensuring adequate nonclinical safety evaluation of drug candidates that generate metabolites considered either to be unique to humans or are present at much higher levels in humans than in preclinical species. We put forward a number of theoretical considerations and present several specific examples where the kinetic behavior of a preformed metabolite given to animals or humans differs from that of the corresponding metabolite generated endogenously from its parent. The potential ramifications of this phenomenon are that the results of toxicity testing of the preformed metabolite may be misleading and fail to characterize the true toxicological contribution of the metabolite when formed from the parent. It is anticipated that such complications would be evident in situations where (a) differences exist in the accumulation of the preformed versus generated metabolites in specific tissues, and (b) the metabolite undergoes sequential metabolism to a downstream product that is toxic, leading to differences in tissue-specific toxicity. Owing to the complex nature of this subject, there is a need to treat drug metabolite issues in safety assessment on a case-by-case basis, in which a knowledge of metabolite kinetics is employed to validate experimental paradigms that entail administration of preformed metabolites to animal models

  3. A new paradigm for known metabolite identification in metabonomics/metabolomics: metabolite identification efficiency.

    Science.gov (United States)

    Everett, Jeremy R

    2015-01-01

    A new paradigm is proposed for assessing confidence in the identification of known metabolites in metabonomics studies using NMR spectroscopy approaches. This new paradigm is based upon the analysis of the amount of metabolite identification information retrieved from NMR spectra relative to the molecular size of the metabolite. Several new indices are proposed including: metabolite identification efficiency (MIE) and metabolite identification carbon efficiency (MICE), both of which can be easily calculated. These indices, together with some guidelines, can be used to provide a better indication of known metabolite identification confidence in metabonomics studies than existing methods. Since known metabolite identification in untargeted metabonomics studies is one of the key bottlenecks facing the science currently, it is hoped that these concepts based on molecular spectroscopic informatics, will find utility in the field.

  4. A New Paradigm for Known Metabolite Identification in Metabonomics/Metabolomics: Metabolite Identification Efficiency

    Directory of Open Access Journals (Sweden)

    Jeremy R. Everett

    2015-01-01

    Full Text Available A new paradigm is proposed for assessing confidence in the identification of known metabolites in metabonomics studies using NMR spectroscopy approaches. This new paradigm is based upon the analysis of the amount of metabolite identification information retrieved from NMR spectra relative to the molecular size of the metabolite. Several new indices are proposed including: metabolite identification efficiency (MIE and metabolite identification carbon efficiency (MICE, both of which can be easily calculated. These indices, together with some guidelines, can be used to provide a better indication of known metabolite identification confidence in metabonomics studies than existing methods. Since known metabolite identification in untargeted metabonomics studies is one of the key bottlenecks facing the science currently, it is hoped that these concepts based on molecular spectroscopic informatics, will find utility in the field.

  5. Importance of Secondary Metabolites for Leaf Beetles (Coleoptera: Chrysomelidae

    Directory of Open Access Journals (Sweden)

    A. N. EKİZ

    2014-06-01

    Full Text Available Leaf beetles (Chrysomelidae are one of the most diverse families of herbivorous insects. Many of them are important agricultural pests and cause remarkable loss of crop and money as well. Plant leaves and roots are primary food source of both larva and adults of leaf beetles. Plants produce many secondary metabolites in reaction to herbivore insects. It is a well-known phenomenon that quantity and variety of secondary metabolites in plant leaves may change in response to insect attacks. Herbivore insects have to deal with such defensive secondary chemicals and overcome either by detoxifying or storing them. Accordingly, many specialist herbivores coevolved with their host plant. Certain phenolic glycosides may reduce leaf beetle feeding. Condensed tannins are anti-herbivore defenses against leaf chewing beetles, including leaf beetles. Flavonoid compounds are feeding deterrents for many flea leaf beetles. Cinnamic acid derivatives are other known feeding deterrents for leaf beetles. Secondary metabolites quantity and nutritional quality of host plants are not only important for feeding but also for providing enemy-free space and suitable oviposition sites.

  6. Proper Sizing of Circulation Pumps

    DEFF Research Database (Denmark)

    Tommerup, Henrik M.; Nørgaard, Jørgen

    2007-01-01

    The paper describes the preliminary results from field tests of replacing various types of old pumps used for circulating water in heating systems in single- and double-family houses with new types of pumps. The tests were carried out in Denmark for the Danish Electricity Savings Trust, but the r......The paper describes the preliminary results from field tests of replacing various types of old pumps used for circulating water in heating systems in single- and double-family houses with new types of pumps. The tests were carried out in Denmark for the Danish Electricity Savings Trust...

  7. Circulating DNA as Potential Biomarker for Cancer Individualized Therapy

    Directory of Open Access Journals (Sweden)

    Shaorong Yu

    2013-09-01

    Full Text Available Cancer individualized therapy often requires for gene mutation analysis of tumor tissue. However, tumor tissue is not always available in clinical practice, particularly from patients with refractory and recurrence disease. Even if patients have sufficient tumor tissue for detection, as development of cancer, the gene status and drug sensitivity of tumor tissues could also change. Hence, screening mutations from primary tumor tissues becomes useless, it’s necessary to find a surrogate tumor tissue for individualized gene screening. Circulating DNA is digested rapidly from blood, which could provide real-time information of the released fragment and make the real-time detection possible. Therefore, it’s expected that circulating DNA could be a potential tumor biomarker for cancer individualized therapy. This review focuses on the biology and clinical utility of circulating DNA mainly on gene mutation detection. Besides, its current status and possible direction in this research area is summarized and discussed objectively.

  8. Sustaining observations of the unsteady ocean circulation.

    Science.gov (United States)

    Frajka-Williams, E

    2014-09-28

    Sustained observations of ocean properties reveal a global warming trend and rising sea levels. These changes have been documented by traditional ship-based measurements of ocean properties, whereas more recent Argo profiling floats and satellite records permit estimates of ocean changes on a near real-time basis. Through these and newer methods of observing the oceans, scientists are moving from quantifying the 'state of the ocean' to monitoring its variability, and distinguishing the physical processes bringing signals of change. In this paper, I give a brief overview of the UK contributions to the physical oceanographic observations, and the role they have played in the wider global observing systems. While temperature and salinity are the primary measurements of physical oceanography, new transbasin mooring arrays also resolve changes in ocean circulation on daily timescales. Emerging technologies permit routine observations at higher-than-ever spatial resolutions. Following this, I then give a personal perspective on the future of sustained observations. New measurement techniques promise exciting discoveries concerning the role of smaller scales and boundary processes in setting the large-scale ocean circulation and the ocean's role in climate. The challenges now facing the scientific community include sustaining critical observations in the case of funding system changes or shifts in government priorities. These long records will enable a determination of the role and response of the ocean to climate change. © 2014 The Author(s) Published by the Royal Society. All rights reserved.

  9. Pharmacologically active plant metabolites as survival strategy products.

    Science.gov (United States)

    Attardo, C; Sartori, F

    2003-01-01

    The fact that plant organisms produce chemical substances that are able to positively or negatively interfere with the processes which regulate human life has been common knowledge since ancient times. One of the numerous possible examples in the infusion of Conium maculatum, better known as Hemlock, a plant belonging to the family umbelliferae, used by the ancient Egyptians to cure skin diseases. The current official pharmacopoeia includes various chemical substances produced by secondary plant metabolisms. For example, the immunosuppressive drugs used to prevent organ transplant rejection and the majority of antibiotics are metabolites produced by fungal organisms, pilocarpin, digitalis, strophantus, salicylic acid and curare are examples of plant organism metabolites. For this reason, there has been an increase in research into plants, based on information on their medicinal use in the areas where they grow. The study of plants in relation to local culture and traditions is known as "ethnobotany". Careful study of the behaviour of sick animals has also led to the discovery of medicinal plants. The study of this subject is known as "zoopharmacognosy". The aim of this article is to discuss the fact that "ad hoc" production of such chemical substances, defined as "secondary metabolites", is one of the modes in which plant organisms respond to unfavourable environmental stimuli, such as an attack by predatory phytophagous animals or an excessive number of plant individuals, even of the same species, in a terrain. In the latter case, the plant organisms produce toxic substances, called "allelopathic" which limit the growth of other individuals. "Secondary metabolites" are produced by metabolic systems that are shunts of the primary systems which, when required, may be activated from the beginning, or increased to the detriment of others. The study of the manner in which such substances are produced is the subject of a new branch of learning called "ecological

  10. The global marine phosphorus cycle: sensitivity to oceanic circulation

    Directory of Open Access Journals (Sweden)

    C. P. Slomp

    2007-01-01

    Full Text Available A new mass balance model for the coupled marine cycles of phosphorus (P and carbon (C is used to examine the relationships between oceanic circulation, primary productivity, and sedimentary burial of reactive P and particulate organic C (POC, on geological time scales. The model explicitly represents the exchanges of water and particulate matter between the continental shelves and the open ocean, and it accounts for the redox-dependent burial of POC and the various forms of reactive P (iron(III-bound P, particulate organic P (POP, authigenic calcium phosphate, and fish debris. Steady state and transient simulations indicate that a slowing down of global ocean circulation decreases primary production in the open ocean, but increases that in the coastal ocean. The latter is due to increased transfer of soluble P from deep ocean water to the shelves, where it fuels primary production and causes increased reactive P burial. While authigenic calcium phosphate accounts for most reactive P burial ocean-wide, enhanced preservation of fish debris may become an important reactive P sink in deep-sea sediments during periods of ocean anoxia. Slower ocean circulation globally increases POC burial, because of enhanced POC preservation under anoxia in deep-sea depositional environments and higher primary productivity along the continental margins. In accordance with geological evidence, the model predicts increased accumulation of reactive P on the continental shelves during and following periods of ocean anoxia.

  11. Evidence of the regulatory effect of Ginkgo biloba extract on skin blood flow and study of its effects on urinary metabolites in healthy humans

    NARCIS (Netherlands)

    Boelsma, E.; Lamers, R.-J.A.N.; Hendriks, H.F.J.; Nesselrooij, J.H.J. van; Roza, L.

    2004-01-01

    Ginkgo biloba extract has been advocated for the improvement of blood circulation in circulatory disorders. This study investigated the effect of the Gingko biloba extract EGb 761 on skin blood flow in healthy volunteers and accompanying changes in urinary metabolites. Twenty-seven healthy

  12. Experimental study of two-phase natural circulation circuit

    Energy Technology Data Exchange (ETDEWEB)

    Lemos, Wanderley Freitas; Su, Jian, E-mail: wlemos@lasme.coppe.ufrj.br, E-mail: sujian@nuclear.ufrj.br [Coordenacao dos Programas de Pos-Graduacao em Engenharia (COPPE/UFRJ), Rio de Janeiro, RJ (Brazil). Programa de Engenharia Nuclear; Faccini, Jose Luiz Horacio, E-mail: faccini@ien.gov.br [Instituto de Engenharia Nuclear (IEN/CNEN-RJ), RIo de Janeiro, RJ (Brazil). Lab. de Termo-Hidraulica Experimental

    2012-07-01

    This paper reports an experimental study on the behavior of fluid flow in natural circulation under single-and two-phase flow conditions. The natural circulation circuit was designed based on concepts of similarity and scale in proportion to the actual operating conditions of a nuclear reactor. This test equipment has similar performance to the passive system for removal of residual heat presents in Advanced Pressurized Water Reactors (A PWR). The experiment was carried out by supplying water to primary and secondary circuits, as well as electrical power resistors installed inside the heater. Power controller has available to adjust the values for supply of electrical power resistors, in order to simulate conditions of decay of power from the nuclear reactor in steady state. Data acquisition system allows the measurement and control of the temperature at different points by means of thermocouples installed at several points along the circuit. The behavior of the phenomenon of natural circulation was monitored by a software with graphical interface, showing the evolution of temperature measurement points and the results stored in digital format spreadsheets. Besides, the natural circulation flow rate was measured by a flowmeter installed on the hot leg. A flow visualization technique was used the for identifying vertical flow regimes of two-phase natural circulation. Finally, the Reynolds Number was calculated for the establishment of a friction factor correlation dependent on the scale geometrical length, height and diameter of the pipe. (author)

  13. Experimental study of two-phase natural circulation circuit

    International Nuclear Information System (INIS)

    Lemos, Wanderley Freitas; Su, Jian; Faccini, Jose Luiz Horacio

    2012-01-01

    This paper reports an experimental study on the behavior of fluid flow in natural circulation under single-and two-phase flow conditions. The natural circulation circuit was designed based on concepts of similarity and scale in proportion to the actual operating conditions of a nuclear reactor. This test equipment has similar performance to the passive system for removal of residual heat presents in Advanced Pressurized Water Reactors (A PWR). The experiment was carried out by supplying water to primary and secondary circuits, as well as electrical power resistors installed inside the heater. Power controller has available to adjust the values for supply of electrical power resistors, in order to simulate conditions of decay of power from the nuclear reactor in steady state. Data acquisition system allows the measurement and control of the temperature at different points by means of thermocouples installed at several points along the circuit. The behavior of the phenomenon of natural circulation was monitored by a software with graphical interface, showing the evolution of temperature measurement points and the results stored in digital format spreadsheets. Besides, the natural circulation flow rate was measured by a flowmeter installed on the hot leg. A flow visualization technique was used the for identifying vertical flow regimes of two-phase natural circulation. Finally, the Reynolds Number was calculated for the establishment of a friction factor correlation dependent on the scale geometrical length, height and diameter of the pipe. (author)

  14. Reevaluation of Kori Unit 4 Natural Circulation Test

    Energy Technology Data Exchange (ETDEWEB)

    Yassin, Nassir [Korea Advanced Institute of Science and Technology, Daejeon (Korea, Republic of); Woo, Sweng Woong [Korea Institute of Nuclear Safety, Daejeon (Korea, Republic of)

    2013-10-15

    The simulation results showed that the natural circulation flow developed by density difference was capable of removing decay heat from the fuel rod. The maximum pellet centerline temperature of the hot channel showed large margin to the pellet melting temperature. The maximum coolant temperature in the hot channel was well below the saturation temperature. If steam generators provide heat sink to the primary coolant system and thus natural circulation is maintained, the integrity of the fuel in the core can be sustained with large margin. Passive cooling of reactor is inevitable in case of failures in forced cooling system such as loss of electric power for cooling pumps. Fukushima accident showed the importance of the passive core cooling. During the commissioning test of PWRs, natural circulation test is performed to demonstrate the passive core cooling by natural convection. The driving force for coolant flow is developed by the density deference along the loop multiplied by the gravitation. Using the data from 'natural circulation test' and 'RCS flow coast down test' of Kori Unit 4, fuel behavior was reevaluated by FRAPTRAN code. RCS natural circulation test of Kori Unit 4 was reevaluated by FRAPTYRAN simulation to study the fuel behavior during the flow coast down transient and at the equilibrium condition in which decay heat transport and RCS flow were stabilized.

  15. Metabolite Profiling of Root Exudates of Common Bean under Phosphorus Deficiency

    Directory of Open Access Journals (Sweden)

    Keitaro Tawaraya

    2014-07-01

    Full Text Available Root exudates improve the nutrient acquisition of plants and affect rhizosphere microbial communities. The plant nutrient status affects the composition of root exudates. The purpose of this study was to examine common bean (Phaseolus vulgaris L. root exudates under phosphorus (P deficiency using a metabolite profiling technique. Common bean plants were grown in a culture solution at P concentrations of 0 (P0, 1 (P1 and 8 (P8 mg P L−1 for 1, 10 and 20 days after transplanting (DAT. Root exudates were collected, and their metabolites were determined by capillary electrophoresis time-of-flight mass spectrometry (CE-TOF MS. The shoot P concentration and dry weight of common bean plants grown at P0 were lower than those grown at P8. One hundred and fifty-nine, 203 and 212 metabolites were identified in the root exudates, and 16% (26/159, 13% (26/203 and 9% (20/212 of metabolites showed a P0/P8 ratio higher than 2.0 at 1, 10 and 20 DAT, respectively. The relative peak areas of several metabolites, including organic acids and amino acids, in root exudates were higher at P0 than at P8. These results suggest that more than 10% of primary and secondary metabolites are induced to exude from roots of common bean by P deficiency.

  16. VanderLaan Circulant Type Matrices

    Directory of Open Access Journals (Sweden)

    Hongyan Pan

    2015-01-01

    Full Text Available Circulant matrices have become a satisfactory tools in control methods for modern complex systems. In the paper, VanderLaan circulant type matrices are presented, which include VanderLaan circulant, left circulant, and g-circulant matrices. The nonsingularity of these special matrices is discussed by the surprising properties of VanderLaan numbers. The exact determinants of VanderLaan circulant type matrices are given by structuring transformation matrices, determinants of well-known tridiagonal matrices, and tridiagonal-like matrices. The explicit inverse matrices of these special matrices are obtained by structuring transformation matrices, inverses of known tridiagonal matrices, and quasi-tridiagonal matrices. Three kinds of norms and lower bound for the spread of VanderLaan circulant and left circulant matrix are given separately. And we gain the spectral norm of VanderLaan g-circulant matrix.

  17. Flavonoid metabolites reduce tumor necrosis factor-α secretion to a greater extent than their precursor compounds in human THP-1 monocytes.

    Science.gov (United States)

    di Gesso, Jessica L; Kerr, Jason S; Zhang, Qingzhi; Raheem, Saki; Yalamanchili, Sai Krishna; O'Hagan, David; Kay, Colin D; O'Connell, Maria A

    2015-06-01

    Flavonoids are generally studied in vitro, in isolation, and as unmetabolized precursor structures. However, in the habitual diet, multiple flavonoids are consumed together and found present in the circulation as complex mixtures of metabolites. Using a unique study design, we investigated the potential for singular or additive anti-inflammatory effects of flavonoid metabolites relative to their precursor structures. Six flavonoids, 14 flavonoid metabolites, and 29 combinations of flavonoids and their metabolites (0.1-10 μM) were screened for their ability to reduce LPS-induced tumor necrosis factor-α (TNF-α) secretion in THP-1 monocytes. One micromolar peonidin-3-glucoside, cyanidin-3-glucoside, and the metabolites isovanillic acid (IVA), IVA-glucuronide, vanillic acid-glucuronide, protocatechuic acid-3-sulfate, and benzoic acid-sulfate significantly reduced TNF-α secretion when in isolation, while there was no effect on TNF-α mRNA expression. Four combinations of metabolites that included 4-hydroxybenzoic acid (4HBA) and/or protocatechuic acid also significantly reduced TNF-α secretion to a greater extent than the precursors or metabolites alone. The effects on LPS-induced IL-1β and IL-10 secretion and mRNA expression were also examined. 4HBA significantly reduced IL-1β secretion but none of the flavonoids or metabolites significantly modified IL-10 secretion. This study provides novel evidence suggesting flavonoid bioactivity results from cumulative or additive effects of circulating metabolites. © 2015 The Authors. Molecular Nutrition & Food Research published by Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  18. Flavonoid metabolites reduce tumor necrosis factor‐α secretion to a greater extent than their precursor compounds in human THP‐1 monocytes

    Science.gov (United States)

    di Gesso, Jessica L.; Kerr, Jason S.; Zhang, Qingzhi; Raheem, Saki; Yalamanchili, Sai Krishna; O'Hagan, David; Kay, Colin D.; O'Connell, Maria A.

    2015-01-01

    1 Scope Flavonoids are generally studied in vitro, in isolation, and as unmetabolized precursor structures. However, in the habitual diet, multiple flavonoids are consumed together and found present in the circulation as complex mixtures of metabolites. Using a unique study design, we investigated the potential for singular or additive anti‐inflammatory effects of flavonoid metabolites relative to their precursor structures. 2 Methods and results Six flavonoids, 14 flavonoid metabolites, and 29 combinations of flavonoids and their metabolites (0.1–10 μM) were screened for their ability to reduce LPS‐induced tumor necrosis factor‐α (TNF‐α) secretion in THP‐1 monocytes. One micromolar peonidin‐3‐glucoside, cyanidin‐3‐glucoside, and the metabolites isovanillic acid (IVA), IVA‐glucuronide, vanillic acid‐glucuronide, protocatechuic acid‐3‐sulfate, and benzoic acid‐sulfate significantly reduced TNF‐α secretion when in isolation, while there was no effect on TNF‐α mRNA expression. Four combinations of metabolites that included 4‐hydroxybenzoic acid (4HBA) and/or protocatechuic acid also significantly reduced TNF‐α secretion to a greater extent than the precursors or metabolites alone. The effects on LPS‐induced IL‐1β and IL‐10 secretion and mRNA expression were also examined. 4HBA significantly reduced IL‐1β secretion but none of the flavonoids or metabolites significantly modified IL‐10 secretion. 3 Conclusion This study provides novel evidence suggesting flavonoid bioactivity results from cumulative or additive effects of circulating metabolites. PMID:25801720

  19. Metabolite profiles of common Stemphylium species

    DEFF Research Database (Denmark)

    Andersen, Birgitte; Solfrizzo, Michelle; Visconti, Angelo

    1995-01-01

    and identified by their chromatographic and spectroscopic data (Rf values, reflectance spectrum, retention index and ultraviolet spectrum). These metabolites have been used for the chemotaxonomical characterization of Stemphylium botryosum, S. herbarum, S. alfalfae, S. majusculum, S. sarciniforme, S. vesicarium...

  20. Detecting beer intake by unique metabolite patterns

    DEFF Research Database (Denmark)

    Gürdeniz, Gözde; Jensen, Morten Georg; Meier, Sebastian

    2016-01-01

    Evaluation of health related effects of beer intake is hampered by the lack of accurate tools for assessing intakes (biomarkers). Therefore, we identified plasma and urine metabolites associated with recent beer intake by untargeted metabolomics and established a characteristic metabolite pattern...... representing raw materials and beer production as a qualitative biomarker of beer intake. In a randomized, crossover, single-blinded meal study (MSt1) 18 participants were given one at a time four different test beverages: strong, regular and non-alcoholic beers and a soft drink. Four participants were...... assigned to have two additional beers (MSt2). In addition to plasma and urine samples, test beverages, wort and hops extract were analyzed by UPLC-QTOF. A unique metabolite pattern reflecting beer metabolome, including metabolites derived from beer raw material (i.e. N-methyl tyramine sulfate and the sum...

  1. METABOLITE CHARACTERIZATION IN SERUM SAMPLES FROM ...

    African Journals Online (AJOL)

    Preferred Customer

    Metabonomics offers a distinct advantage over other tests as it can be ... Metabolic profiling in heart disease has also been successfully ... resonances of the small metabolites showing fingerprints of serum metabolomic profile (Figure. 3).

  2. Secondary metabolites of cyanobacteria Nostoc sp.

    Science.gov (United States)

    Kobayashi, Akio; Kajiyama, Shin-Ichiro

    1998-03-01

    Cyanobacteria attracted much attention recently because of their secondary metabolites with potent biological activities and unusual structures. This paper reviews some recent studies on the isolation, structural, elucidation and biological activities of the bioactive compounds from cyanobacteria Nostoc species.

  3. Metabolite Profiling of Red Sea Corals

    KAUST Repository

    Ortega, Jovhana Alejandra

    2016-01-01

    that provide insights into the specific nature of the symbiosis. Our analysis also revealed aquatic pollutants, which suggests that metabolite profiling might be used for monitoring pollution levels and assessing environmental impact.

  4. Hydrophobicity and charge shape cellular metabolite concentrations.

    Directory of Open Access Journals (Sweden)

    Arren Bar-Even

    2011-10-01

    Full Text Available What governs the concentrations of metabolites within living cells? Beyond specific metabolic and enzymatic considerations, are there global trends that affect their values? We hypothesize that the physico-chemical properties of metabolites considerably affect their in-vivo concentrations. The recently achieved experimental capability to measure the concentrations of many metabolites simultaneously has made the testing of this hypothesis possible. Here, we analyze such recently available data sets of metabolite concentrations within E. coli, S. cerevisiae, B. subtilis and human. Overall, these data sets encompass more than twenty conditions, each containing dozens (28-108 of simultaneously measured metabolites. We test for correlations with various physico-chemical properties and find that the number of charged atoms, non-polar surface area, lipophilicity and solubility consistently correlate with concentration. In most data sets, a change in one of these properties elicits a ~100 fold increase in metabolite concentrations. We find that the non-polar surface area and number of charged atoms account for almost half of the variation in concentrations in the most reliable and comprehensive data set. Analyzing specific groups of metabolites, such as amino-acids or phosphorylated nucleotides, reveals even a higher dependence of concentration on hydrophobicity. We suggest that these findings can be explained by evolutionary constraints imposed on metabolite concentrations and discuss possible selective pressures that can account for them. These include the reduction of solute leakage through the lipid membrane, avoidance of deleterious aggregates and reduction of non-specific hydrophobic binding. By highlighting the global constraints imposed on metabolic pathways, future research could shed light onto aspects of biochemical evolution and the chemical constraints that bound metabolic engineering efforts.

  5. Urinary metabolites of tetrahydronorharman in the rat

    Energy Technology Data Exchange (ETDEWEB)

    Greiner, B.; Rommelspacher, H.

    1982-01-01

    The metabolism of THN in the rat was studied in vivo by use of /sup 14/C-radiolabelled compound. Structures of major urinary metabolites were determined by exact spectral data. Their concentrations were measured by liquid scintillation counting. It was found that THN is submitted to endogenous transformation, and that the excreted derivatives form three groups of similar concentration: unchanged substance, hydroxylated/conjugated compounds, and aromatic metabolites. Structures and proposed pathways are summed in diagram.

  6. Urinary metabolites of tetrahydronorharman in the rat

    International Nuclear Information System (INIS)

    Greiner, B.; Rommelspacher, H.

    1982-01-01

    The metabolism of THN in the rat was studied in vivo by use of 14 C-radiolabelled compound. Structures of major urinary metabolites were determined by exact spectral data. Their concentrations were measured by liquid scintillation counting. It was found that THN is submitted to endogenous transformation, and that the excreted derivatives form three groups of similar concentration: unchanged substance, hydroxylated/conjugated compounds, and aromatic metabolites. Structures and proposed pathways are summed in diagram

  7. GPCR-Mediated Signaling of Metabolites

    DEFF Research Database (Denmark)

    Husted, Anna Sofie; Trauelsen, Mette; Rudenko, Olga

    2017-01-01

    microbiota target primarily enteroendocrine, neuronal, and immune cells in the lamina propria of the gut mucosa and the liver and, through these tissues, the rest of the body. In contrast, metabolites from the intermediary metabolism act mainly as metabolic stress-induced autocrine and paracrine signals...... and obesity. The concept of key metabolites as ligands for specific GPCRs has broadened our understanding of metabolic signaling significantly and provides a number of novel potential drug targets....

  8. Cellular Immune Reactions of the Sunn Pest, Eurygaster integriceps, to the Entomopathogenic Fungus, Beauveria bassiana and Its Secondary Metabolites

    Science.gov (United States)

    Zibaee, Arash; Bandani, Ali Reza; Talaei-Hassanlouei, Reza; Malagoli, Davide

    2011-01-01

    In this study, five morphological types of circulating hemocytes were recognized in the hemolymph of the adult sunn pest, Eurygaster integriceps Puton (Hemiptera: Scutelleridae), namely prohemocytes, plasmatocytes, granulocytes, adipohemocytes, and oenocytoids. The effects of the secondary metabolites of the entomopathogenic fungus Beauveria bassiana on cellular immune defenses of Eurygaster integriceps were investigated. The results showed that the fungal secondary metabolites inhibited phagocytic activity of E. integriceps hemocytes and hampered nodule formation. A reduction of phenoloxidase activity was also observed. The data suggest that B. bassiana produce secondary metabolites that disable several immune mechanisms allowing the fungus to overcome and then kill its host. This characteristic makes B. bassiana a promising model for biological control of insect pests such as E. integriceps. PMID:22233481

  9. New metabolites of hongdenafil, homosildenafil and hydroxyhomosildenafil.

    Science.gov (United States)

    Yeo, Miseon; Park, Yujin; Lee, Heesang; Choe, Sanggil; Baek, Seung-Hoon; Kim, Hye Kyung; Pyo, Jae Sung

    2018-02-05

    Recently, illegal sildenafil analogues have emerged, causing serious social issues. In spite of the importance of sildenafil analogues, their metabolic profiles or clinical effects have not been reported yet. In this study, new metabolites of illegal sildenafil analogues such as hongdenafil, homosildenafil, and hydroxyhomosildenafil were determined using liquid chromatography quadrupole-time of flight mass spectrometry (LC-Q-TOF-MS) and tandem mass spectrometry (LC-Q-TOF-MS/MS). To prepare metabolic samples, in vitro and in vivo studies were performed. For in vivo metabolites analysis, urine and feces samples of rats treated with sildenafil analogues were analyzed. For in vitro metabolites analysis, human liver microsomes incubated with sildenafil analogues were extracted and analyzed. All metabolites were characterized by LC-Q-TOF-MS and LC-Q-TOF-MS/MS. As a result, five, six, and seven metabolites were determined in hongdenafil, homosildenafil, and hydroxyhomosildenafil treated samples, respectively. These results could be applied to forensic science and other analytical fields. Moreover, these newly identified metabolites could be used as fundamental data to determine the side effect and toxicity of illegal sildenafil analogues. Copyright © 2017 Elsevier B.V. All rights reserved.

  10. Metabolites of cannabidiol identified in human urine.

    Science.gov (United States)

    Harvey, D J; Mechoulam, R

    1990-03-01

    1. Urine from a dystonic patient treated with cannabidiol (CBD) was examined by g.l.c.-mass spectrometry for CBD metabolites. Metabolites were identified as their trimethylsilyl (TMS), [2H9]TMS, and methyl ester/TMS derivatives and as the TMS derivatives of the product of lithium aluminium deuteride reduction. 2. Thirty-three metabolites were identified in addition to unmetabolized CBD, and a further four metabolites were partially characterized. 3. The major metabolic route was hydroxylation and oxidation at C-7 followed by further hydroxylation in the pentyl and propenyl groups to give 1"-, 2"-, 3"-, 4"- and 10-hydroxy derivatives of CBD-7-oic acid. Other metabolites, mainly acids, were formed by beta-oxidation and related biotransformations from the pentyl side-chain and these were also hydroxylated at C-6 or C-7. The major oxidized metabolite was CBD-7-oic acid containing a hydroxyethyl side-chain. 4. Two 8,9-dihydroxy compounds, presumably derived from the corresponding epoxide were identified. 5. Also present were several cyclized cannabinoids including delta-6- and delta-1-tetrahydrocannabinol and cannabinol. 6. This is the first metabolic study of CBD in humans; most observed metabolic routes were typical of those found for CBD and related cannabinoids in other species.

  11. Development of thermohydraulic software for PWR reactors with natural circulation

    International Nuclear Information System (INIS)

    Chasseur, Alfredo F.; Rauschert, A.; Delmastro, Dario F.

    2009-01-01

    The basics concepts about the development of software for steady state analysis of a reactor with natural circulations, in the primary circuit, are exposed. The reactor type is pressurized light water. The equations, correlations and flux diagrams of the source code of the software developed are shown. The source code of the software was written in FORTRAN 77 making use of modular technique, this save development effort and release of news versions is simplified. (author)

  12. Metabolite kinetics: formation of acetaminophen from deuterated and nondeuterated phenacetin and acetanilide on acetaminophen sulfation kinetics in the perfused rat liver preparation

    International Nuclear Information System (INIS)

    Pang, K.S.; Waller, L.; Horning, M.G.; Chan, K.K.

    1982-01-01

    The role of hepatic intrinsic clearance for metabolite formation from various precursors on subsequent metabolite elimination was was investigated in the once-through perfused rat liver preparation. Two pairs of acetaminophen precursors: [ 14 C] phenacetin-d5 and [ 3 H] phenacetin-do, [ 14 C] acetanilide and [ 3 H] phenacetin were delivered by constant flow (10 ml/min/liver) either by normal or retrograde perfusion to the rat liver preparations. The extents of acetaminophen sulfation were compared within the same preparation. The data showed that the higher the hepatocellular activity (intrinsic clearance) for acetaminophen formation, the greater the extent of subsequent acetaminophen sulfation. The findings were explained on the basis of blood transit time and metabolite duration time. Because of blood having only a finite transit time in liver, the longer the drug requires for metabolite formation, the less time will remain for metabolite sulfation and the less will be the degree of subsequent sulfation. Conversely, when the drug forms the primary metabolite rapidly, a longer time will remain for the metabolite to be sulfated in liver to result in a greater degree of metabolite sulfation. Finally, the effects of hepatic intrinsic clearances for metabolite formation and zonal distribution of enzyme systems for metabolite formation and elimination in liver are discussed

  13. Journalism as Cultures of Circulation

    DEFF Research Database (Denmark)

    Bødker, Henrik

    2013-01-01

    The universe of journalism has always consisted of interspersed texts, meanings and practices. Yet, much journalism research has often isolated either texts and/or contexts and as such assumed relations between professional practices, informed (rational) readers and (conceived) core texts...... of journalism. It is, however, more important than ever to shift attention away from texts to the processes through which they are circulated. This is partly because the many cultural forms of journalism (textual, institutional, technological, material, behavioural and imagined) are undergoing significant......, likes, comments, searches, journalist roles, writing and reading positions and identities etc. Such forms will be traced within the mediation of a specific event with the overall aim of beginning a theorization of the landscape of journalism as highly interrelated cultures of circulation....

  14. Radioisotopic evaluation of portal circulation

    International Nuclear Information System (INIS)

    Maliska, C.; Rosenthal, D.

    1986-01-01

    The use of a radio-tracer of portal circulation through the intestine, should prevent cruel punctures in the portal-vein or spleen as it is usually the case with traditional methods in the study of portal-system. The absorption of I-131 and Tc-99m, previously cheked in rabbits presented similar results in dogs. The time of circulation between terminal large-intestine and the liver (t-RF) was determined by external counting at hepatic level by recording radioactivity variation-time. In healthy animals the t-RF was from 20to 60 seconds, with average time of 42 seconds. In 2 animals with partial binding of portal-vein the t-RF went up to 110 and 120 seconds. (Author) [pt

  15. Ocean circulation generated magnetic signals

    DEFF Research Database (Denmark)

    Manoj, C.; Kuvshinov, A.; Maus, S.

    2006-01-01

    Conducting ocean water, as it flows through the Earth's magnetic field, generates secondary electric and magnetic fields. An assessment of the ocean-generated magnetic fields and their detectability may be of importance for geomagnetism and oceanography. Motivated by the clear identification...... of ocean tidal signatures in the CHAMP magnetic field data we estimate the ocean magnetic signals of steady flow using a global 3-D EM numerical solution. The required velocity data are from the ECCO ocean circulation experiment and alternatively from the OCCAM model for higher resolution. We assume...... of the magnetic field, as compared to the ECCO simulation. Besides the expected signatures of the global circulation patterns, we find significant seasonal variability of ocean magnetic signals in the Indian and Western Pacific Oceans. Compared to seasonal variation, interannual variations produce weaker signals....

  16. Observations of Local Seychelles Circulation

    Science.gov (United States)

    2015-09-30

    1 DISTRIBUTION STATEMENT A. Approved for public release; distribution is unlimited. Observations of Local Seychelles Circulation Geno...goal for the proposed work is to develop predictive capabilities for physical oceanography for the Seychelles region in support of locally relevant...observations in the Seychelles region that will lead to long-term data collection efforts. In collaboration with local partnerships, we will carry out

  17. Circulating nucleic acids and evolution.

    Science.gov (United States)

    Anker, Philippe; Stroun, Maurice

    2012-06-01

    J.B. Lamarck in 1809 was the first to present a theory of evolution. He proposed it was due to the adaptation of species to environmental changes, this adaptation being acquired by the offspring. In 1868, Darwin suggested that cells excrete gemmules, which circulate through the body and reach the gonads where they are transmitted to the next generation. His main argument came from graft hybrids. In the fifties and sixties, Russian geneticists, rejecting neo-Darwinism, said that acquired characteristics were the basis of evolution. The main experiments on which they based their theory were the transmission of hereditary characteristics by a special technique of grafting between two varieties of plants. We repeated this kind of experiment and also succeeded in obtaining hereditary modifications of the pupil plants that acquired some characteristics of the mentor variety. Rather than adopting the views of the Russian scientists, we suggested that DNA was circulating between the mentor and pupil plants. Hirata's group have shown recently, by using molecular techniques such as cloning, RFLP PCR and sequencing some genes of their graft hybrids of pepper plants, that transfer of informative molecules from the mentor to the pupil plant does exist. Nucleic acids are actively released by cells; they circulate in the body. They can transform oncogenically or trigger antibody response but the only genetic transformation showing that DNA can go from the soma to the germen comes from graft hybrids. This suggests that circulating nucleic acids, in this case DNA, like Darwin's gemmules, play a role in the mechanism of evolution.

  18. Improvement of Classification of Enterprise Circulating Funds

    OpenAIRE

    Rohanova Hanna O.

    2014-01-01

    The goal of the article lies in revelation of possibilities of increase of efficiency of managing enterprise circulating funds by means of improvement of their classification features. Having analysed approaches of many economists to classification of enterprise circulating funds, systemised and supplementing them, the article offers grouping classification features of enterprise circulating funds. In the result of the study the article offers an expanded classification of circulating funds, ...

  19. Hall Effect Gyrators and Circulators

    Science.gov (United States)

    Viola, Giovanni; DiVincenzo, David P.

    2014-04-01

    The electronic circulator and its close relative the gyrator are invaluable tools for noise management and signal routing in the current generation of low-temperature microwave systems for the implementation of new quantum technologies. The current implementation of these devices using the Faraday effect is satisfactory but requires a bulky structure whose physical dimension is close to the microwave wavelength employed. The Hall effect is an alternative nonreciprocal effect that can also be used to produce desired device functionality. We review earlier efforts to use an Ohmically contacted four-terminal Hall bar, explaining why this approach leads to unacceptably high device loss. We find that capacitive coupling to such a Hall conductor has much greater promise for achieving good circulator and gyrator functionality. We formulate a classical Ohm-Hall analysis for calculating the properties of such a device, and show how this classical theory simplifies remarkably in the limiting case of the Hall angle approaching 90°. In this limit, we find that either a four-terminal or a three-terminal capacitive device can give excellent circulator behavior, with device dimensions far smaller than the ac wavelength. An experiment is proposed to achieve GHz-band gyration in millimeter (and smaller) scale structures employing either semiconductor heterostructure or graphene Hall conductors. An inductively coupled scheme for realizing a Hall gyrator is also analyzed.

  20. Early concepts and charts of ocean circulation

    Science.gov (United States)

    Peterson, R. G.; Stramma, L.; Kortum, G.

    little about them was reported in the Classical works. Following the dark and Middle Ages, when little progress was made, the voyages of discovery brought startling observations of many of Earth's most important ocean currents, such as the North and South Equatorial currents, the Gulf Stream, the Agulhas, Kuroshio, Peru, and Guinea currents, and others. The Gulf Stream appears to have been mapped as early as 1525 (Ribeiro) on the basis of Spanish pilot charts. Some currents were found to be westward, in the direction of the primum mobile as expected by theologians and philosophers, while others were not. The fifteenth through seventeenth centuries were marked by attainments of knowledge that increasingly taxed the abilities of science writers to reconcile new information with accepted doctrine. Consequences of this were descriptions of ocean circulation that questioned doctrine, yet were limited by it (Martyr; Gilbert; Bourne; Varen), while other descriptions disdainfully violated observation (Kircher; Happel). The expectation of a continuous westward oceanic flow around Earth in the direction of the primum mobile was so pervasive that it became central to arguments about a need for a passage through or around the Canadian north, and thus weighed significantly on the exploration and mapping of North America. Religious influences and the conceptual importance of the primum mobile waned by the close of the Renaissance and wind came to be seen as the primary cause of ocean currents (Dampier). The Gulf Stream (Franklin) and other North Atlantic flow patterns (de Brahm), as well as the southern Agulhas Current (Rennell), were mapped in the mid-to-late eighteenth century. Significant advances beyond these in determining the global ocean circulation came only after the routine determination of longitude at sea was instituted. The introduction of the marine chronometer in the late eighteenth century (Harrison) made this possible. By the end of the eighteenth century it was

  1. Encoders for block-circulant LDPC codes

    Science.gov (United States)

    Divsalar, Dariush (Inventor); Abbasfar, Aliazam (Inventor); Jones, Christopher R. (Inventor); Dolinar, Samuel J. (Inventor); Thorpe, Jeremy C. (Inventor); Andrews, Kenneth S. (Inventor); Yao, Kung (Inventor)

    2009-01-01

    Methods and apparatus to encode message input symbols in accordance with an accumulate-repeat-accumulate code with repetition three or four are disclosed. Block circulant matrices are used. A first method and apparatus make use of the block-circulant structure of the parity check matrix. A second method and apparatus use block-circulant generator matrices.

  2. Nutrient pumping by submesoscale circulations in the mauritanian upwelling system

    Science.gov (United States)

    Hosegood, P. J.; Nightingale, P. D.; Rees, A. P.; Widdicombe, C. E.; Woodward, E. M. S.; Clark, D. R.; Torres, R. J.

    2017-12-01

    Observations made within a cold filament in the Mauritanian upwelling system demonstrate that intense submesoscale circulations at the peripheral edges of the filament are likely responsible for anomalously high levels of observed primary productivity by resupplying nutrients to the euphotic zone. Measurements made on the shelf within the recently upwelled water reveal that primary production (PP) of 8.2 gC/m-2 day-1 was supported by nitrate concentrations (NC) of 8 mmol m-3. Towards the front that defined the edge of the filament containing the upwelled water as it was transported offshore, PP dropped to 1.6 gC m-2 day-1 whilst NC dropped to 5.5 mmol m-3. Thus, whilst the observed nutrients on the shelf accounted for 90% of new production, this value dropped to ∼60% near the filament's front after accounting for vertical turbulent fluxes and Ekman pumping. We demonstrate that the N15 was likely to have been supplied at the front by submesoscale circulations that were directly measured as intense vertical velocities ⩾100 m day-1 by a drifting acoustic Doppler current profiler that crossed a submesoscale surface temperature front. At the same time, a recently released tracer was subducted out of the mixed layer within 24 h of release, providing direct evidence that the frontal circulations were capable of accessing the reservoir of nutrients beneath the pycnocline. The susceptibility of the filament edge to submesoscale instabilities was demonstrated by O(1) Rossby numbers at horizontal scales of 1-10 km. The frontal circulations are consistent with instabilities arising from a wind-driven nonlinear Ekman buoyancy flux generated by the persistent northerly wind stress that has a down-front component at the northern edge of the inshore section of the filament. The prevalence of submesoscale instabilities and their associated vertical circulations are proposed to be a key mechanism operating at sub-grid scales and sustaining new production throughout the upwelling

  3. Benchmark analysis of three main circulation pump sequential trip event at Ignalina NPP

    International Nuclear Information System (INIS)

    Uspuras, E.; Kaliatka, A.; Urbonas, R.

    2001-01-01

    The Ignalina Nuclear Power Plant is a twin-unit with two RBMK-1500 reactors. The primary circuit consists of two symmetrical loops. Eight Main Circulation Pumps (MCPs) at the Ignalina NPP are employed for the coolant water forced circulation through the reactor core. The MCPs are joined in groups of four pumps for each loop (three for normal operation and one on standby). This paper presents the benchmark analysis of three main circulation pump sequential trip event at RBMK-1500 using RELAP5 code. During this event all three MCPs in one circulation loop at Unit 2 Ignalina NPP were tripped one after another, because of inadvertent activation of the fire protection system. The comparison of calculated and measured parameters led us to establish realistic thermal hydraulic characteristics of different main circulation circuit components and to verify the model of drum separators pressure and water level controllers.(author)

  4. Pregnancy-Induced Changes in the Pharmacokinetics of Caffeine and Its Metabolites

    Science.gov (United States)

    Yu, Tian; Campbell, Sarah C.; Stockmann, Chris; Tak, Casey; Schoen, Katherine; Clark, Erin A. S.; Varner, Michael W.; Spigarelli, Michael G.; Sherwin, Catherine M. T.

    2017-01-01

    This study sought to assess the pharmacokinetic (PK) changes of caffeine and its CYP1A2 metabolites across the 3 trimesters of pregnancy. A prospective, multicenter PK study was conducted among 59 pregnant women (93.2% white) who were studied once during a trimester. One beverage with 30–95 mg caffeine was consumed, and a blood/urine sample was collected within 1 hour postingestion. Concentrations of caffeine and its primary metabolites were quantified from serum and urine by LC-MS/MS. There was a significant increase in dose-normalized caffeine serum and urine concentrations between the first and third trimesters (Ptheobromine concentrations. This study identified decreased caffeine metabolism and an increase in the active metabolite theophylline concentrations during pregnancy, especially in the third trimester, revealing evidence of the large role that pregnancy plays in influencing caffeine metabolism. PMID:26358647

  5. Amenorrhea - primary

    Science.gov (United States)

    ... of periods - primary Images Primary amenorrhea Normal uterine anatomy (cut section) Absence of menstruation (amenorrhea) References Bulun SE. The physiology and pathology of the female reproductive axis. In: ...

  6. Detecting Beer Intake by Unique Metabolite Patterns.

    Science.gov (United States)

    Gürdeniz, Gözde; Jensen, Morten Georg; Meier, Sebastian; Bech, Lene; Lund, Erik; Dragsted, Lars Ove

    2016-12-02

    Evaluation of the health related effects of beer intake is hampered by the lack of accurate tools for assessing intakes (biomarkers). Therefore, we identified plasma and urine metabolites associated with recent beer intake by untargeted metabolomics and established a characteristic metabolite pattern representing raw materials and beer production as a qualitative biomarker of beer intake. In a randomized, crossover, single-blinded meal study (MSt1), 18 participants were given, one at a time, four different test beverages: strong, regular, and nonalcoholic beers and a soft drink. Four participants were assigned to have two additional beers (MSt2). In addition to plasma and urine samples, test beverages, wort, and hops extract were analyzed by UPLC-QTOF. A unique metabolite pattern reflecting beer metabolome, including metabolites derived from beer raw material (i.e., N-methyl tyramine sulfate and the sum of iso-α-acids and tricyclohumols) and the production process (i.e., pyro-glutamyl proline and 2-ethyl malate), was selected to establish a compliance biomarker model for detection of beer intake based on MSt1. The model predicted the MSt2 samples collected before and up to 12 h after beer intake correctly (AUC = 1). A biomarker model including four metabolites representing both beer raw materials and production steps provided a specific and accurate tool for measurement of beer consumption.

  7. Plant metabolites and nutritional quality of vegetables.

    Science.gov (United States)

    Hounsome, N; Hounsome, B; Tomos, D; Edwards-Jones, G

    2008-05-01

    Vegetables are an important part of the human diet and a major source of biologically active substances such as vitamins, dietary fiber, antioxidants, and cholesterol-lowering compounds. Despite a large amount of information on this topic, the nutritional quality of vegetables has not been defined. Historically, the value of many plant nutrients and health-promoting compounds was discovered by trial and error. By the turn of the century, the application of chromatography, mass spectrometry, infrared spectrometry, and nuclear magnetic resonance allowed quantitative and qualitative measurements of a large number of plant metabolites. Approximately 50000 metabolites have been elucidated in plants, and it is predicted that the final number will exceed 200000. Most of them have unknown function. Metabolites such as carbohydrates, organic and amino acids, vitamins, hormones, flavonoids, phenolics, and glucosinolates are essential for plant growth, development, stress adaptation, and defense. Besides the importance for the plant itself, such metabolites determine the nutritional quality of food, color, taste, smell, antioxidative, anticarcinogenic, antihypertension, anti-inflammatory, antimicrobial, immunostimulating, and cholesterol-lowering properties. This review is focused on major plant metabolites that characterize the nutritional quality of vegetables, and methods of their analysis.

  8. Secondary metabolites in fungus-plant interactions

    Science.gov (United States)

    Pusztahelyi, Tünde; Holb, Imre J.; Pócsi, István

    2015-01-01

    Fungi and plants are rich sources of thousands of secondary metabolites. The genetically coded possibilities for secondary metabolite production, the stimuli of the production, and the special phytotoxins basically determine the microscopic fungi-host plant interactions and the pathogenic lifestyle of fungi. The review introduces plant secondary metabolites usually with antifungal effect as well as the importance of signaling molecules in induced systemic resistance and systemic acquired resistance processes. The review also concerns the mimicking of plant effector molecules like auxins, gibberellins and abscisic acid by fungal secondary metabolites that modulate plant growth or even can subvert the plant defense responses such as programmed cell death to gain nutrients for fungal growth and colonization. It also looks through the special secondary metabolite production and host selective toxins of some significant fungal pathogens and the plant response in form of phytoalexin production. New results coming from genome and transcriptional analyses in context of selected fungal pathogens and their hosts are also discussed. PMID:26300892

  9. Functional metabolite assemblies—a review

    Science.gov (United States)

    Aizen, Ruth; Tao, Kai; Rencus-Lazar, Sigal; Gazit, Ehud

    2018-05-01

    Metabolites are essential for the normal operation of cells and fulfill various physiological functions. It was recently found that in several metabolic disorders, the associated metabolites could self-assemble to generate amyloid-like structures, similar to canonical protein amyloids that have a role in neurodegenerative disorders. Yet, assemblies with typical amyloid characteristics are also known to have physiological function. In addition, many non-natural proteins and peptides presenting amyloidal properties have been used for the fabrication of functional nanomaterials. Similarly, functional metabolite assemblies are also found in nature, demonstrating various physiological roles. A notable example is the structural color formed by guanine crystals or fluorescent crystals in feline eyes responsible for enhanced night vision. Moreover, some metabolites have been used for the in vitro fabrication of functional materials, such as glycine crystals presenting remarkable piezoelectric properties or indigo films used to assemble organic semi-conductive electronic devices. Therefore, we believe that the study of metabolite assemblies is not only important in order to understand their role in normal physiology and in pathology, but also paves a new route in exploring the fabrication of organic, bio-compatible materials.

  10. Pharmaceutically active secondary metabolites of marine actinobacteria.

    Science.gov (United States)

    Manivasagan, Panchanathan; Venkatesan, Jayachandran; Sivakumar, Kannan; Kim, Se-Kwon

    2014-04-01

    Marine actinobacteria are one of the most efficient groups of secondary metabolite producers and are very important from an industrial point of view. Many representatives of the order Actinomycetales are prolific producers of thousands of biologically active secondary metabolites. Actinobacteria from terrestrial sources have been studied and screened since the 1950s, for many important antibiotics, anticancer, antitumor and immunosuppressive agents. However, frequent rediscovery of the same compounds from the terrestrial actinobacteria has made them less attractive for screening programs in the recent years. At the same time, actinobacteria isolated from the marine environment have currently received considerable attention due to the structural diversity and unique biological activities of their secondary metabolites. They are efficient producers of new secondary metabolites that show a range of biological activities including antibacterial, antifungal, anticancer, antitumor, cytotoxic, cytostatic, anti-inflammatory, anti-parasitic, anti-malaria, antiviral, antioxidant, anti-angiogenesis, etc. In this review, an evaluation is made on the current status of research on marine actinobacteria yielding pharmaceutically active secondary metabolites. Bioactive compounds from marine actinobacteria possess distinct chemical structures that may form the basis for synthesis of new drugs that could be used to combat resistant pathogens. With the increasing advancement in science and technology, there would be a greater demand for new bioactive compounds synthesized by actinobacteria from various marine sources in future. Copyright © 2013 Elsevier GmbH. All rights reserved.

  11. Genetic determinants of circulating sphingolipid concentrations in European populations.

    Directory of Open Access Journals (Sweden)

    Andrew A Hicks

    2009-10-01

    Full Text Available Sphingolipids have essential roles as structural components of cell membranes and in cell signalling, and disruption of their metabolism causes several diseases, with diverse neurological, psychiatric, and metabolic consequences. Increasingly, variants within a few of the genes that encode enzymes involved in sphingolipid metabolism are being associated with complex disease phenotypes. Direct experimental evidence supports a role of specific sphingolipid species in several common complex chronic disease processes including atherosclerotic plaque formation, myocardial infarction (MI, cardiomyopathy, pancreatic beta-cell failure, insulin resistance, and type 2 diabetes mellitus. Therefore, sphingolipids represent novel and important intermediate phenotypes for genetic analysis, yet little is known about the major genetic variants that influence their circulating levels in the general population. We performed a genome-wide association study (GWAS between 318,237 single-nucleotide polymorphisms (SNPs and levels of circulating sphingomyelin (SM, dihydrosphingomyelin (Dih-SM, ceramide (Cer, and glucosylceramide (GluCer single lipid species (33 traits; and 43 matched metabolite ratios measured in 4,400 subjects from five diverse European populations. Associated variants (32 in five genomic regions were identified with genome-wide significant corrected p-values ranging down to 9.08x10(-66. The strongest associations were observed in or near 7 genes functionally involved in ceramide biosynthesis and trafficking: SPTLC3, LASS4, SGPP1, ATP10D, and FADS1-3. Variants in 3 loci (ATP10D, FADS3, and SPTLC3 associate with MI in a series of three German MI studies. An additional 70 variants across 23 candidate genes involved in sphingolipid-metabolizing pathways also demonstrate association (p = 10(-4 or less. Circulating concentrations of several key components in sphingolipid metabolism are thus under strong genetic control, and variants in these loci can be

  12. Diuron metabolites and urothelial cytotoxicity: In vivo, in vitro and molecular approaches

    International Nuclear Information System (INIS)

    Da Rocha, Mitscheli S.; Arnold, Lora L.; Dodmane, Puttappa R.; Pennington, Karen L.; Qiu, Fang; De Camargo, João Lauro V.; Cohen, Samuel M.

    2013-01-01

    Diuron is carcinogenic to the rat urinary bladder at high dietary levels. The proposed mode of action (MOA) for diuron is urothelial cytotoxicity and necrosis followed by regenerative urothelial hyperplasia. Diuron-induced urothelial cytotoxicity is not due to urinary solids. Diuron is extensively metabolized, and in rats, N-(3,4-dichlorophenyl)urea (DCPU) and 4,5-dichloro-2-hydroxyphenyl urea (2-OH-DCPU) were the predominant urinary metabolites; lesser metabolites included N-(3,4-dichlorophenyl)-3-methylurea (DCPMU) and trace levels of 3,4-dichloroaniline (DCA). In humans, DCPMU and DCPU have been found in the urine after a case of product abuse. To aid in elucidating the MOA of diuron and to evaluate the metabolites that are responsible for the diuron toxicity in the bladder epithelium, we investigated the urinary concentrations of metabolites in male Wistar rats treated with 2500 ppm of diuron, the urothelial cytotoxicity in vitro of the metabolites and their gene expression profiles. DCPU was found in rat urine at concentrations substantially greater than the in vitro IC50 and induced more gene expression alterations than the other metabolites tested. 2-OH-DCPU was present in urine at a concentration approximately half of the in vitro IC50, whereas DCPMU and DCA were present in urine at concentrations well below the IC50. For the diuron-induced MOA for the rat bladder, we suggest that DCPU is the primary metabolite responsible for the urothelial cytotoxicity with some contribution also by 2-OH-DCPU. This study supports a MOA for diuron-induced bladder effects in rats consisting of metabolism to DCPU (and 2-OH-DCPU to a lesser extent), concentration and excretion in urine, urothelial cytotoxicity, and regenerative proliferation

  13. Diuron metabolites and urothelial cytotoxicity: in vivo, in vitro and molecular approaches.

    Science.gov (United States)

    Da Rocha, Mitscheli S; Arnold, Lora L; Dodmane, Puttappa R; Pennington, Karen L; Qiu, Fang; De Camargo, João Lauro V; Cohen, Samuel M

    2013-12-15

    Diuron is carcinogenic to the rat urinary bladder at high dietary levels. The proposed mode of action (MOA) for diuron is urothelial cytotoxicity and necrosis followed by regenerative urothelial hyperplasia. Diuron-induced urothelial cytotoxicity is not due to urinary solids. Diuron is extensively metabolized, and in rats, N-(3,4-dichlorophenyl)urea (DCPU) and 4,5-dichloro-2-hydroxyphenyl urea (2-OH-DCPU) were the predominant urinary metabolites; lesser metabolites included N-(3,4-dichlorophenyl)-3-methylurea (DCPMU) and trace levels of 3,4-dichloroaniline (DCA). In humans, DCPMU and DCPU have been found in the urine after a case of product abuse. To aid in elucidating the MOA of diuron and to evaluate the metabolites that are responsible for the diuron toxicity in the bladder epithelium, we investigated the urinary concentrations of metabolites in male Wistar rats treated with 2500ppm of diuron, the urothelial cytotoxicity in vitro of the metabolites and their gene expression profiles. DCPU was found in rat urine at concentrations substantially greater than the in vitro IC50 and induced more gene expression alterations than the other metabolites tested. 2-OH-DCPU was present in urine at a concentration approximately half of the in vitro IC50, whereas DCPMU and DCA were present in urine at concentrations well below the IC50. For the diuron-induced MOA for the rat bladder, we suggest that DCPU is the primary metabolite responsible for the urothelial cytotoxicity with some contribution also by 2-OH-DCPU. This study supports a MOA for diuron-induced bladder effects in rats consisting of metabolism to DCPU (and 2-OH-DCPU to a lesser extent), concentration and excretion in urine, urothelial cytotoxicity, and regenerative proliferation. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  14. Urinary phthalate metabolite concentrations in relation to history of infertility and use of assisted reproductive technology.

    Science.gov (United States)

    Alur, Snigdha; Wang, Hongyue; Hoeger, Kathy; Swan, Shanna H; Sathyanarayana, Sheela; Redmon, Bruce J; Nguyen, Ruby; Barrett, Emily S

    2015-11-01

    To examine urinary phthalate metabolite concentrations in pregnant women with planned pregnancies in relation to history of infertility and use of assisted reproductive technology (ART). Phthalate metabolite concentrations were measured in first-trimester urine samples collected from women participating in a prospective pregnancy cohort study. Prenatal clinics. A total of 750 women, of whom 86 had a history of infertility. Forty-one women used ART to conceive. None. Primary outcomes were concentrations of four metabolites of diethylhexyl phthalate (DEHP) and their molar sum (∑DEHP). Multivariable analyses compared phthalate metabolite levels in [1] women reporting a history of infertility vs. those who did not (comparison group); and [2] those who used ART to conceive the index pregnancy vs. women with a history of infertility who did not use ART. Among women with a history of infertility, ∑DEHP was significantly lower in women who conceived after ART compared with those who did not (geometric mean ratio: 0.83; 95% confidence interval 0.71-0.98). Similar significant associations were observed for all of the individual DEHP metabolites. There were no differences in DEHP metabolite concentrations between women with a history of infertility and the comparison group. Women who used ART to conceive had lower first-trimester phthalate metabolite concentrations than women with a history of infertility who did not use ART. Further research is needed to explore whether those pursuing fertility treatments take precautions to avoid exposure to environmental toxins, to improve treatment outcomes. Copyright © 2015 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

  15. Plant-Derived Polyphenols in Human Health: Biological Activity, Metabolites and Putative Molecular Targets.

    Science.gov (United States)

    Olivares-Vicente, Marilo; Barrajon-Catalan, Enrique; Herranz-Lopez, Maria; Segura-Carretero, Antonio; Joven, Jorge; Encinar, Jose Antonio; Micol, Vicente

    2018-01-01

    Hibiscus sabdariffa, Lippia citriodora, Rosmarinus officinalis and Olea europaea, are rich in bioactive compounds that represent most of the phenolic compounds' families and have exhibited potential benefits in human health. These plants have been used in folk medicine for their potential therapeutic properties in human chronic diseases. Recent evidence leads to postulate that polyphenols may account for such effects. Nevertheless, the compounds or metabolites that are responsible for reaching the molecular targets are unknown. data based on studies directly using complex extracts on cellular models, without considering metabolic aspects, have limited applicability. In contrast, studies exploring the absorption process, metabolites in the blood circulation and tissues have become essential to identify the intracellular final effectors that are responsible for extracts bioactivity. Once the cellular metabolites are identified using high-resolution mass spectrometry, docking techniques suppose a unique tool for virtually screening a large number of compounds on selected targets in order to elucidate their potential mechanisms. we provide an updated overview of the in vitro and in vivo studies on the toxicity, absorption, permeability, pharmacokinetics and cellular metabolism of bioactive compounds derived from the abovementioned plants to identify the potential compounds that are responsible for the observed health effects. we propose the use of targeted metabolomics followed by in silico studies to virtually screen identified metabolites on selected protein targets, in combination with the use of the candidate metabolites in cellular models, as the methods of choice for elucidating the molecular mechanisms of these compounds. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  16. Detection of Volatile Metabolites Derived from Garlic (Allium sativum in Human Urine

    Directory of Open Access Journals (Sweden)

    Laura Scheffler

    2016-12-01

    Full Text Available The metabolism and excretion of flavor constituents of garlic, a common plant used in flavoring foods and attributed with several health benefits, in humans is not fully understood. Likewise, the physiologically active principles of garlic have not been fully clarified to date. It is possible that not only the parent compounds present in garlic but also its metabolites are responsible for the specific physiological properties of garlic, including its influence on the characteristic body odor signature of humans after garlic consumption. Accordingly, the aim of this study was to investigate potential garlic-derived metabolites in human urine. To this aim, 14 sets of urine samples were obtained from 12 volunteers, whereby each set comprised one sample that was collected prior to consumption of food-relevant concentrations of garlic, followed by five to eight subsequent samples after garlic consumption that covered a time interval of up to 26 h. The samples were analyzed chemo-analytically using gas chromatography-mass spectrometry/olfactometry (GC-MS/O, as well as sensorially by a trained human panel. The analyses revealed three different garlic-derived metabolites in urine, namely allyl methyl sulfide (AMS, allyl methyl sulfoxide (AMSO and allyl methyl sulfone (AMSO2, confirming our previous findings on human milk metabolite composition. The excretion rates of these metabolites into urine were strongly time-dependent with distinct inter-individual differences. These findings indicate that the volatile odorant fraction of garlic is heavily biotransformed in humans, opening up a window into substance circulation within the human body with potential wider ramifications in view of physiological effects of this aromatic plant that is appreciated by humans in their daily diet.

  17. Quantitative profiling of polar metabolites in herbal medicine injections for multivariate statistical evaluation based on independence principal component analysis.

    Directory of Open Access Journals (Sweden)

    Miaomiao Jiang

    Full Text Available Botanical primary metabolites extensively exist in herbal medicine injections (HMIs, but often were ignored to control. With the limitation of bias towards hydrophilic substances, the primary metabolites with strong polarity, such as saccharides, amino acids and organic acids, are usually difficult to detect by the routinely applied reversed-phase chromatographic fingerprint technology. In this study, a proton nuclear magnetic resonance (1H NMR profiling method was developed for efficient identification and quantification of small polar molecules, mostly primary metabolites in HMIs. A commonly used medicine, Danhong injection (DHI, was employed as a model. With the developed method, 23 primary metabolites together with 7 polyphenolic acids were simultaneously identified, of which 13 metabolites with fully separated proton signals were quantified and employed for further multivariate quality control assay. The quantitative 1H NMR method was validated with good linearity, precision, repeatability, stability and accuracy. Based on independence principal component analysis (IPCA, the contents of 13 metabolites were characterized and dimensionally reduced into the first two independence principal components (IPCs. IPC1 and IPC2 were then used to calculate the upper control limits (with 99% confidence ellipsoids of χ2 and Hotelling T2 control charts. Through the constructed upper control limits, the proposed method was successfully applied to 36 batches of DHI to examine the out-of control sample with the perturbed levels of succinate, malonate, glucose, fructose, salvianic acid and protocatechuic aldehyde. The integrated strategy has provided a reliable approach to identify and quantify multiple polar metabolites of DHI in one fingerprinting spectrum, and it has also assisted in the establishment of IPCA models for the multivariate statistical evaluation of HMIs.

  18. A Wind Tunnel Model to Explore Unsteady Circulation Control for General Aviation Applications

    Science.gov (United States)

    Cagle, Christopher M.; Jones, Gregory S.

    2002-01-01

    Circulation Control airfoils have been demonstrated to provide substantial improvements in lift over conventional airfoils. The General Aviation Circular Control model is an attempt to address some of the concerns of this technique. The primary focus is to substantially reduce the amount of air mass flow by implementing unsteady flow. This paper describes a wind tunnel model that implements unsteady circulation control by pulsing internal pneumatic valves and details some preliminary results from the first test entry.

  19. Diarrhea caused by circulating agents.

    Science.gov (United States)

    Fabian, Elisabeth; Kump, Patrizia; Krejs, Guenter J

    2012-09-01

    Circulating agents cause intestinal secretion or changes in motility with decreased intestinal transit time, resulting in secretory-type diarrhea. Secretory diarrhea as opposed to osmotic diarrhea is characterized by large-volume, watery stools, often more than 1 L per day; by persistence of diarrhea when patients fast; and by the fact that on analysis of stool-water, measured osmolarity is identical to that calculated from the electrolytes present. Although sodium plays the main role in water and electrolyte absorption, chloride is the major ion involved in secretion. Copyright © 2012 Elsevier Inc. All rights reserved.

  20. Study on scaling law of PWR natural circulation with motion condition

    International Nuclear Information System (INIS)

    Lu Donghua; Xiao Zejun; Chen Bingde

    2009-01-01

    For some nuclear reactors installed on automobiles, boats or deep sea vehicles, it is an important way to investigate their system safety by performing natural circulation experiments under motion condition. This paper studied the natural circulation on moving plants based on work of static natural circulation scaling method. With rigid motion theory, acceleration at each point was obtained on primary system and introduced to momentum equation. Thus a set of motion similar criteria were obtained. Furthermore, equal and unequal height simulation were analyzed. As to the unequal one, non isochronous simulation was needed for displacement and angular acceleration. (authors)

  1. Influence of reactor design on the establishment of natural circulation in pool-type LMFBR

    International Nuclear Information System (INIS)

    Durham, M.E.

    1976-01-01

    The general principles involved in establishing natural circulation in a pool-type liquid metal cooled fast breeder reactor following loss of a.c. supplies are elucidated and the effects of design features by use of the computer code MELANI are quantified. It is shown that natural circulation can provide a feasible means of emergency core cooling in addition to that provided by pony motors. The choice of primary pump rundown time has a significant effect in controlling peak core outlet temperatures in the hypothetical case of natural circulation alone being the core heat removal process. (author)

  2. Simvastatin (SV) metabolites in mouse tissues

    International Nuclear Information System (INIS)

    Duncan, C.A.; Vickers, S.

    1990-01-01

    SV, a semisynthetic analog of lovastatin, is hydrolyzed in vivo to its hydroxy acid (SVA), a potent inhibitor of HMG CoA reductase (HR). Thus SV lowers plasma cholesterol. SV is a substrate for mixed function oxidases whereas SVA undergoes lactonization and β-oxidation. Male CD-1 mice were dosed orally with a combination of ( 14 C)SV and ( 3 H)SVA at 25 mg/kg of each, bled and killed at 0.5, 2 and 4 hours. Labeled SV, SVA, 6'exomethylene SV (I), 6'CH 2 OH-SV (II), 6'COOH-SV (III) and a β-oxidized metabolite (IV) were assayed in liver, bile, kidneys, testes and plasma by RIDA. Levels of potential and active HR inhibitors in liver were 10 to 40 fold higher than in other tissues. II and III, in which the configuration at 6' is inverted, may be 2 metabolites of I. Metabolites I-III are inhibitors of HR in their hydroxy acid forms. Qualitatively ( 14 C)SV and ( 3 H)SVA were metabolized similarly (consistent with their proposed interconversion). However 3 H-SVA, I-III (including hydroxy acid forms) achieved higher concentrations than corresponding 14 C compounds (except in gall bladder bile). Major radioactive metabolites in liver were II-IV (including hydroxy acid forms). These metabolites have also been reported in rat tissues. In bile a large fraction of either label was unidentified polar metabolites. The presence of IV indicated that mice (like rats) are not good models for SV metabolism in man

  3. Metabolite production by species of Stemphylium

    DEFF Research Database (Denmark)

    Olsen, Kresten Jon Kromphardt; Rossman, Amy; Andersen, Birgitte

    2018-01-01

    metabolites were found to be important for distinguishing species, while some unknown metabolites were also found to have important roles in distinguishing species of Stemphylium. This study is the first of its kind to investigate the chemical potential of Stemphylium across the whole genus.......Morphology and phylogeny has been used to distinguish members of the plant pathogenic fungal genus Stemphylium. A third method for distinguishing species is by chemotaxonomy. The main goal of the present study was to investigate the chemical potential of Stemphylium via HPLC-UV-MS analysis, while...

  4. Animal bioavailability of defined xenobiotic lignin metabolites

    International Nuclear Information System (INIS)

    Sandermann, H. Jr.; Arjmand, M.; Gennity, I.; Winkler, R.; Struble, C.B.; Aschbacher, P.W.

    1990-01-01

    Lignin has been recognized as a major component of bound pesticide residues in plants and is thought to be undigestible in animals. Two defined ring-U- 14 C-labeled chloroaniline/lignin metabolites have now been fed to rats, where a release of ∼66% of the bound xenobiotic occurred in the form of simple chloroaniline derivatives. The observed high degree of bioavailability indicates that bound pesticidal residues may possess ecotoxicological significance. In parallel studies, the white-rot fungus Phanerochaete chrysosporium was more efficient, and a soil system was much less efficient, in the degradation of the [ring-U- 14 C]chloroaniline/lignin metabolites

  5. Experiences with loss of natural circulation events, performed experiments, analysis, computations and development of operational documents

    International Nuclear Information System (INIS)

    Nagy, L.; Varju, A.; Nagy, S.

    1996-01-01

    The refuelling of the unit 4 was started on 18 June, 1988. At the time of the event the reactor was in cold shutdown state, with atmospheric pressure, the reactor head was removed. On June 30 the operational personnel performed a planned switch over of natural circulation from loops 4, 6 to loops 1, 3. In the meantime the effectiveness of the core cooling by natural circulation decreased sharply for about 3 hour-period. After switching over the natural circulation among the loops the operating personnel isolated the loops 4., 6. and started to drain them. Nitrogen used to drain the loops was unintentionally injected into the loops in operation and large amount of primary coolant was pushed out from the SG primary side to the reactor vessel. The operators tried to stop the disturbance of natural circulation by starting the booster pump of make-up system periodically to the working loops. During this injection the personnel performed venting few times to take away the gas-air mixture from the top of the SG primary headers. After all the restoration of the natural circulation was achieved by continuous venting the SG headers. During 1993 annual refuelling outage of Unit 2 at Paks NPP a deterioration of natural circulation in reactor coolant system occurred. A special maintenance task was being performed to repair the cladding of the sealing bellows between the reactor vessel and reactor cavity

  6. Intestinal circulation during inhalation anesthesia

    International Nuclear Information System (INIS)

    Tverskoy, M.; Gelman, S.; Fowler, K.C.; Bradley, E.L.

    1985-01-01

    This study was designed to evaluate the influence of inhalational agents on the intestinal circulation in an isolated loop preparation. Sixty dogs were studied, using three intestinal segments from each dog. Selected intestinal segments were pumped with aortic blood at a constant pressure of 100 mmHg. A mixture of 86 Rb and 9-microns spheres labeled with 141 Ce was injected into the arterial cannula supplying the intestinal loop, while mesenteric venous blood was collected for activity counting. A very strong and significant correlation was found between rubidium clearance and microsphere entrapment (r = 0.97, P less than 0.0001). Nitrous oxide anesthesia was accompanied by a higher vascular resistance (VR), lower flow (F), rubidium clearance (Cl-Rb), and microspheres entrapment (Cl-Sph) than pentobarbital anesthesia, indicating that the vascular bed in the intestinal segment was constricted and flow (total and nutritive) decreased. Halothane, enflurane, and isoflurane anesthesia were accompanied by a much lower arteriovenous oxygen content difference (AVDO 2 ) and oxygen uptake than pentobarbital or nitrous oxide. Compared with pentobarbital, enflurane anesthesia was not accompanied by marked differences in VR, F, Cl-Rb, and Cl-Sph; halothane at 2 MAC decreased VR and increased F and Cl-Rb while isoflurane increased VR and decreased F. alpha-Adrenoceptor blockade with phentolamine (1 mg . kg-1) abolished isoflurane-induced vasoconstriction, suggesting that the increase in VR was mediated via circulating catecholamines

  7. Roadmap for cardiovascular circulation model

    Science.gov (United States)

    Bradley, Christopher P.; Suresh, Vinod; Mithraratne, Kumar; Muller, Alexandre; Ho, Harvey; Ladd, David; Hellevik, Leif R.; Omholt, Stig W.; Chase, J. Geoffrey; Müller, Lucas O.; Watanabe, Sansuke M.; Blanco, Pablo J.; de Bono, Bernard; Hunter, Peter J.

    2016-01-01

    Abstract Computational models of many aspects of the mammalian cardiovascular circulation have been developed. Indeed, along with orthopaedics, this area of physiology is one that has attracted much interest from engineers, presumably because the equations governing blood flow in the vascular system are well understood and can be solved with well‐established numerical techniques. Unfortunately, there have been only a few attempts to create a comprehensive public domain resource for cardiovascular researchers. In this paper we propose a roadmap for developing an open source cardiovascular circulation model. The model should be registered to the musculo‐skeletal system. The computational infrastructure for the cardiovascular model should provide for near real‐time computation of blood flow and pressure in all parts of the body. The model should deal with vascular beds in all tissues, and the computational infrastructure for the model should provide links into CellML models of cell function and tissue function. In this work we review the literature associated with 1D blood flow modelling in the cardiovascular system, discuss model encoding standards, software and a model repository. We then describe the coordinate systems used to define the vascular geometry, derive the equations and discuss the implementation of these coupled equations in the open source computational software OpenCMISS. Finally, some preliminary results are presented and plans outlined for the next steps in the development of the model, the computational software and the graphical user interface for accessing the model. PMID:27506597

  8. Gut microbial metabolites of polyunsaturated fatty acids correlate with specific fecal bacteria and serum markers of metabolic syndrome in obese women.

    Science.gov (United States)

    Druart, Céline; Dewulf, Evelyne M; Cani, Patrice D; Neyrinck, Audrey M; Thissen, Jean-Paul; Delzenne, Nathalie M

    2014-04-01

    The aim of this human study was to assess the influence of prebiotic-induced gut microbiota modulation on PUFA-derived bacterial metabolites production. Therefore, we analyzed the circulating fatty acid profile including CLA/CLnA in obese women treated during 3 months with inulin-type fructan prebiotics. In these patients, we had already determined gut microbiota composition by phylogenetic microarray and qPCR analysis of 16S rDNA. Some PUFA-derived bacterial metabolites were detected in the serum of obese patients. Despite the prebiotic-induced modulation of gut microbiota, including changes in CLA/CLnA-producing bacteria, the treatment did not impact significantly on the circulating level of these metabolites. However, some PUFA-derived bacterial metabolites were positively correlated with specific fecal bacteria (Bifidobacterium spp., Eubacterium ventriosum and Lactobacillus spp.) and inversely correlated with serum cholesterol (total, LDL, HDL). These correlations suggest a potential beneficial effect of some of these metabolites but this remains to be confirmed by further investigation.

  9. Field estimates of groundwater circulation depths in two mountainous watersheds in the western U.S. and the effect of deep circulation on solute concentrations in streamflow

    Science.gov (United States)

    Frisbee, Marty D.; Tolley, Douglas G.; Wilson, John L.

    2017-04-01

    Estimates of groundwater circulation depths based on field data are lacking. These data are critical to inform and refine hydrogeologic models of mountainous watersheds, and to quantify depth and time dependencies of weathering processes in watersheds. Here we test two competing hypotheses on the role of geology and geologic setting in deep groundwater circulation and the role of deep groundwater in the geochemical evolution of streams and springs. We test these hypotheses in two mountainous watersheds that have distinctly different geologic settings (one crystalline, metamorphic bedrock and the other volcanic bedrock). Estimated circulation depths for springs in both watersheds range from 0.6 to 1.6 km and may be as great as 2.5 km. These estimated groundwater circulation depths are much deeper than commonly modeled depths suggesting that we may be forcing groundwater flow paths too shallow in models. In addition, the spatial relationships of groundwater circulation depths are different between the two watersheds. Groundwater circulation depths in the crystalline bedrock watershed increase with decreasing elevation indicative of topography-driven groundwater flow. This relationship is not present in the volcanic bedrock watershed suggesting that both the source of fracturing (tectonic versus volcanic) and increased primary porosity in the volcanic bedrock play a role in deep groundwater circulation. The results from the crystalline bedrock watershed also indicate that relatively deep groundwater circulation can occur at local scales in headwater drainages less than 9.0 km2 and at larger fractions than commonly perceived. Deep groundwater is a primary control on streamflow processes and solute concentrations in both watersheds.

  10. Effects of atorvastatin metabolites on induction of drug-metabolizing enzymes and membrane transporters through human pregnane X receptor

    Science.gov (United States)

    Hoffart, E; Ghebreghiorghis, L; Nussler, AK; Thasler, WE; Weiss, TS; Schwab, M; Burk, O

    2012-01-01

    BACKGROUND AND PURPOSE Atorvastatin metabolites differ in their potential for drug interaction because of differential inhibition of drug-metabolizing enzymes and transporters. We here investigate whether they exert differential effects on the induction of these genes via activation of pregnane X receptor (PXR) and constitutive androstane receptor (CAR). EXPERIMENTAL APPROACH Ligand binding to PXR or CAR was analysed by mammalian two-hybrid assembly and promoter/reporter gene assays. Additionally, surface plasmon resonance was used to analyse ligand binding to CAR. Primary human hepatocytes were treated with atorvastatin metabolites, and mRNA and protein expression of PXR-regulated genes was measured. Two-hybrid co-activator interaction and co-repressor release assays were utilized to elucidate the molecular mechanism of PXR activation. KEY RESULTS All atorvastatin metabolites induced the assembly of PXR and activated CYP3A4 promoter activity. Ligand binding to CAR could not be proven. In primary human hepatocytes, the para-hydroxy metabolite markedly reduced or abolished induction of cytochrome P450 and transporter genes. While significant differences in co-activator recruitment were not observed, para-hydroxy atorvastatin demonstrated only 50% release of co-repressors. CONCLUSIONS AND IMPLICATIONS Atorvastatin metabolites are ligands of PXR but not of CAR. Atorvastatin metabolites demonstrate differential induction of PXR target genes, which results from impaired release of co-repressors. Consequently, the properties of drug metabolites have to be taken into account when analysing PXR-dependent induction of drug metabolism and transport. The drug interaction potential of the active metabolite, para-hydroxy atorvastatin, might be lower than that of the parent compound. PMID:21913896

  11. The impact of age-class and social context on fecal glucocorticoid metabolite levels in free-ranging male giraffes.

    Science.gov (United States)

    Wolf, T E; Bennett, N C; Burroughs, R; Ganswindt, A

    2018-01-01

    One of the primary sources of perceived stress is the social environment of an animal and the interactions with conspecifics. An essential component of the response to a stressor is the activation of the hypothalamic-pituitary-adrenocortical axis, which results amongst others in a temporal increase in circulating glucocorticoid (GC) levels. Giraffes occur in a highly flexible fission-fusion social system and group compositions can change on a daily basis, with bulls establishing an age-related dominance hierarchy and showing a roaming strategy in the search for fertile females. The aim of this study was to non-invasively monitor the influence of different group compositions (mixed sex groups vs. all-male groups) on GC concentrations in free ranging giraffe bulls of different age classes. We collected fecal samples from free-ranging giraffe bulls for 12months in a South African Private Game Reserve to examine age- and social context-related patterns of fecal GC metabolite (fGCM) concentrations. We found that fGCM levels in giraffe bulls are age-class dependent, as well asassociated with changes in the social environment. Independently of the social setting, bulls of the youngest age class exhibited the highest fGCM levels compared to bulls of the other two older age-classes, with differences most pronounced when the bulls are associated in all-male groups. In contrast, an almost reversed picture appears when looking at the fGCM levels of sexually active individuals in mixed sex groups, where highest levels were found for the bulls in the oldest age-class, and the lowest for the bulls in the youngest age-class. The study stresses the importance to taking factors such asage-related status and social settings into account, when interpreting fGCM levels in free ranging giraffes. Copyright © 2017 Elsevier Inc. All rights reserved.

  12. Simulation of natural circulation on an integral type experimental facility, MASLWR

    Energy Technology Data Exchange (ETDEWEB)

    Chung, Youngjong; Lim, Sungwon; Ha, Jaejoo [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of)

    2013-05-15

    The OSU MASLWR test facility was reconfigured to eliminate a recurring grounding problem and improve facility reliability in anticipation of conducting an IAEA International Collaborative Standard Problem (ICSP). The purpose of ICSP is to provide experimental data on flow instability phenomena under natural circulation conditions and coupled containment/reactor vessel behavior in integral-type reactors, and to evaluate system code capabilities to predict natural circulation phenomena for integral type PWR, by simulating an integrated experiment. A natural circulation in the primary side during various core powers is analyzed using TASS/SMR code for the integral type experimental facility. The calculation results show higher steady state primary flow than experiment. If it matches the initial flow with experiment, it shows lower primary flow than experiment according to the increase of power. The code predictions may be improved by applying a Reynolds number dependent form loss coefficient to accurately account for unrecoverable pressure losses.

  13. Organic metabolites produced by Vibrio parahaemolyticus strain ...

    African Journals Online (AJOL)

    Identification and action of several antibacterial metabolites produced by a fish pathogen Vibrio parahaemolyticus strain An3 from marine ecosystem of Goa has been demonstrated. Antibacterial activity of the crude cell extract of the test bacterium has been evaluated against indicator pathogenic bacterial strains such as ...

  14. Chemical composition, secondary metabolites, in vitro gas ...

    African Journals Online (AJOL)

    Chemical composition, secondary metabolites, in vitro gas production characteristics and acceptability study of some forage for ruminant feeding in South-Western Nigeria. ... Chemical composition and qualitative analysis of saponins, phenol and steroids of the plants were determined. In vitro gas production (IVGP) was ...

  15. Secondary metabolites from Scorzonera latifolia roots

    Czech Academy of Sciences Publication Activity Database

    Acikara, O. B.; Šmejkal, K.; Cvačka, Josef; Buděšínský, Miloš; Dračínský, Martin; Saltan, G.

    2015-01-01

    Roč. 81, č. 16 (2015), PM167 ISSN 0032-0943. [GA 2015. International Congress and Annual Meeting of the Society for Medicinal Plant and Natural Product Research /63./. 23.08.2015-27.08.2015, Budapest] Institutional support: RVO:61388963 Keywords : medical plant * metabolites * Asteraceae Subject RIV: CB - Analytical Chemistry, Separation

  16. Antibacterial activity of secondary metabolites isolated from ...

    African Journals Online (AJOL)

    Aghomotsegin

    2015-10-28

    Oct 28, 2015 ... Alternaria spp. are cosmopolitan mould fungi and can be found in soils ... the secondary metabolites products from A. alternata and ..... Zone of inhibition (mm) of test bacterial strains to fungal products and standard antibiotics. Fungal ... marine actinomycetes from pulicat, Muttukadu, and Ennore estuaries.

  17. Identification of a new metabolite of GHB

    DEFF Research Database (Denmark)

    Petersen, Ida Nymann; Tortzen, Christian; Kristensen, Jesper Langgaard

    2013-01-01

    Gamma-hydroxybutyric acid (GHB) is an important analyte in clinical and forensic toxicology with a narrow detection window of 3-6 h. In the search of improved detection methods, the existence in vivo of a glucuronated GHB metabolite (GHB-GLUC) was hypothesized. Chemically pure standards of GHB...

  18. Streptopyrrole: An antimicrobial metabolite from Streptomyces armeniacus

    DEFF Research Database (Denmark)

    Breinholt, J.; Gürtler, Hanne; Kjær, Anders

    1998-01-01

    A colourless, crystalline metabolite, C14H12ClNO4, named streptopyrrole, has been isolated from submerged fermentation cultures of Streptomyces armeniacus by extraction, followed by chromatographic purification. Its tricyclic molecular framework, seemingly without natural product precedents. as w...

  19. Microbial metabolism part 13 metabolites of hesperetin

    Science.gov (United States)

    The fungal culture, Mucor ramannianus (ATCC 2628) transformed hesperitin to four metabolites: 4'-methoxy -5, 7, 8, 3'-tetrahydroxyflavanone (8-hydroxyhesperetin), 5, 7, 3', 4'-tetrahydroxyflavanone (eriodictyol), 4'-methoxy-5, 3'-dihydroxyflavanone 7-sulfate (hesperetin 7-sulfate) and 5, 7, 3'-tri...

  20. Human pharmacokinetics of proguanil and its metabolites

    DEFF Research Database (Denmark)

    Bygbjerg, Ib Christian; Ravn, P; Rønn, A

    1987-01-01

    The pharmacokinetics of proguanil and its metabolites cycloguanil and p-chlorophenylbiguanide were studied in five healthy volunteers taking 200 mg orally for 14 days. A highly sensitive and specific high-performance liquid chromatographic assay was applied, clearly identifying all three compounds...

  1. Microfluidic Platform for Circulating Tumor Cells Isolation

    Energy Technology Data Exchange (ETDEWEB)

    Figueras-Mari, I.; Rodriguez-Trujillo, L.; Samitier-Marti, J.

    2016-07-01

    Circulating tumor cells (CTCs) are released from primary tumors into the bloodstream and transported to distant organs, promoting metastasis, which is known to be responsible for most cancer‐related deaths. Currently tumors are not found until symptoms appear or by chance when the patient undergoes a medical test, which in both situations can be too late. Once a tumor is found it is studied from tissue samples obtained directly from the patient in an invasive way. This invasive procedure is known as biopsy and apart from being invasive, it is costly, time consuming and can sometimes be painful and even risky for the patients’ health condition. Therefore, CTCs detection in blood also addressed as “liquid biopsy” would be very useful because by running routine blood analysis CTCs could be detected and collected suggesting tumor presence. However, due to the scarce presence in blood of these cells and to the huge amount of contamination from other cellular components a perfect method providing good capture and purity of CTCs has not been developed yet. In this project, a spiral size sorter microfluidic device has been manufactured and tested in order to determine its performance and limitations. Device performance was tested with different dilutions of healthy donor blood samples mixed with 30 micron particles simulating CTCs. The results obtained from these experiments show very good CTC recovery of up to 100% and the depletion of blood cellular components is around 99.9%. (Author)

  2. Theoretical investigation on the steady-state natural circulation characteristics of a new type of pressurized water reactor

    International Nuclear Information System (INIS)

    Gou Junli; Qiu Suizheng; Su Guanghui; Jia Dounan

    2006-01-01

    This article presents a theoretical investigation on the steady-state natural circulation characteristics of a new type of pressurized water reactor. Through numerically solving the one-dimensional steady-state single-phase conservative equations for the primary circuit and the steady-state two-phase drift-flux conservative equations for the secondary side of the steam generator, the natural circulation characteristics were studied. On the basis of the preliminary calculation analysis, it was found that natural circulation mass flow rate was proportional to the exponential function of the power and that the value of the exponent is related to the operating conditions of the secondary side of the steam generator. The higher the outlet pressure of the secondary side of the steam generator, the higher the primary natural circulation mass flow rate. The larger height difference between the core center and the steam generator center is favorable for the heat removal capacity of the natural circulation. (authors)

  3. Single and two-phase natural circulation in Westinghouse pressurized water reactor simulators: Phenomena, analysis and scaling

    International Nuclear Information System (INIS)

    Schultz, R.R.; Chapman, J.C.; Kukita, Y.; Motley, F.E.; Stumpf, H.; Chen, Y.S.; Tasaka, K.

    1987-01-01

    Natural circulation data obtained in the 1/48 scale W four loop PWR simulator - the Large Scale Test Facility (LSTF) are discussed and summarized. Core cooling modes, the primary fluid state, the primary loop mass flow and localized natural circulation phenomena occurring in the steam generator are presented. TRAC-PF1 LSTF model (using both a 1 U-tube and a 3 U-tube steam generator model) analyses of the LSTF natural circulation data including the SG recirculation patterns are presented and compared to the data. The LSTF data are then compared to similar natural circulation data obtained in the Primarkreislaufe (PKL) and the Semiscale facilities. Based on the 1/48 to 1/1705 scaling range which exists between the facilities, the implications of these data towrard natural circulation behavior in commercial plants are briefly discussed

  4. Differential metabolite levels in response to spawning-induced inappetence in Atlantic salmon Salmo salar.

    Science.gov (United States)

    Cipriano, Rocco C; Smith, McKenzie L; Vermeersch, Kathleen A; Dove, Alistair D M; Styczynski, Mark P

    2015-03-01

    Atlantic salmon Salmo salar undergo months-long inappetence during spawning, but it is not known whether this inappetence is a pathological state or one for which the fish are adapted. Recent work has shown that inappetent whale sharks can exhibit circulating metabolite profiles similar to ketosis known to occur in humans during starvation. In this work, metabolite profiling was used to explore differences in analyte profiles between a cohort of inappetent spawning run Atlantic salmon and captively reared animals that were fed up to and through the time of sampling. The two classes of animals were easily distinguished by their metabolite profiles. The sea-run fish had elevated ɷ-9 fatty acids relative to the domestic feeding animals, while other fatty acid concentrations were reduced. Sugar alcohols were generally elevated in inappetent animals, suggesting potentially novel metabolic responses or pathways in fish that feature these compounds. Compounds expected to indicate a pathological catabolic state were not more abundant in the sea-run fish, suggesting that the animals, while inappetent, were not stressed in an unnatural way. These findings demonstrate the power of discovery-based metabolomics for exploring biochemistry in poorly understood animal models. Copyright © 2015 Elsevier Inc. All rights reserved.

  5. Uranus atmospheric dynamics and circulation

    Science.gov (United States)

    Allison, Michael; Beebe, Reta F.; Conrath, Barney J.; Hinson, David P.; Ingersoll, Andrew P.

    1991-01-01

    The observations, models, and theories relevant to the atmospheric dynamics and meteorology of Uranus are discussed. The available models for the large-scale heat transport and atmospheric dynamics as well as diagnostic interpretations of the Voyager data are reviewed. Some pertinent ideas and questions regarding the global circulation balance are considered, partly in comparison with other planetary atmospheres. The available data indicate atmospheric rotation at midlatitudes nearly 200 m/s faster than that of the planetary magnetic field. Analysis of the dynamical deformation of the shape and size of isobaric surfaces measured by the Voyager radio-occultation experiment suggests a subrotating equator at comparable altitudes. Infrared temperature retrievals above the cloud deck indicate a smaller equator-to-pole contrast than expected for purely radiative-convective equilibrium, but show local variations implying a latitudinally correlated decrease with altitude in the cloud-tracked wind.

  6. Improvement of Classification of Enterprise Circulating Funds

    Directory of Open Access Journals (Sweden)

    Rohanova Hanna O.

    2014-02-01

    Full Text Available The goal of the article lies in revelation of possibilities of increase of efficiency of managing enterprise circulating funds by means of improvement of their classification features. Having analysed approaches of many economists to classification of enterprise circulating funds, systemised and supplementing them, the article offers grouping classification features of enterprise circulating funds. In the result of the study the article offers an expanded classification of circulating funds, which clearly shows the role of circulating funds in managing enterprise finance and economy in general. The article supplements and groups classification features of enterprise circulating funds by: the organisation level, functioning character, sources of formation and their cost, and level of management efficiency. The article shows that the provided grouping of classification features of circulating funds allows exerting all-sided and purposeful influence upon indicators of efficiency of circulating funds functioning and facilitates their rational management in general. The prospect of further studies in this direction is identification of the level of attraction of loan resources by production enterprises for financing circulating funds.

  7. NPP Krsko natural circulation performance evaluation

    International Nuclear Information System (INIS)

    Segon, Velimir; Bajs, Tomislav; Frogheri, Monica

    1999-01-01

    The present document deals with an evaluation of the natural circulation performance of the Krsko nuclear power plant. Two calculation have been performed using the NPP Krsko nodalization (both similar to the LOBI A2-77 natural circulation experiment) - the first with the present steam generators at NPP Krsko (Westinghouse, 18% plugged), the second with the future steam generators (Siemens, 0% plugged). The results were evaluated using the natural circulation flow map derived in /1/, and were compared to evaluate the influence of the new steam generators on the natural circulation performance. (author)

  8. A blood circulation model for reference man

    Energy Technology Data Exchange (ETDEWEB)

    Leggett, R.W.; Eckerman, K.F. [Oak Ridge National Lab., TN (United States); Williams, L.R. [Indiana Univ., South Bend, IN (United States). Div. of Liberal Arts and Sciences

    1996-12-31

    A dynamic blood circulation model that predicts the movement and gradual dispersion of a bolus of material in the circulation after its intravenous injection into an adult human. The main purpose of the model is improve the dosimetry of internally deposited radionuclides that decay in the circulation to a significant extent. The model partitions the blood volume into 24 separate organs or tissues, right heart chamber, left heart chamber, pulmonary circulation, arterial outflow to the aorta and large arteries, and venous return via the large veins. Model results were compared to data obtained from injection of carbon 11 labeled carbon monoxide or rubidium 86.

  9. A blood circulation model for reference man

    International Nuclear Information System (INIS)

    Leggett, R.W.; Eckerman, K.F.; Williams, L.R.

    1996-01-01

    A dynamic blood circulation model that predicts the movement and gradual dispersion of a bolus of material in the circulation after its intravenous injection into an adult human. The main purpose of the model is improve the dosimetry of internally deposited radionuclides that decay in the circulation to a significant extent. The model partitions the blood volume into 24 separate organs or tissues, right heart chamber, left heart chamber, pulmonary circulation, arterial outflow to the aorta and large arteries, and venous return via the large veins. Model results were compared to data obtained from injection of carbon 11 labeled carbon monoxide or rubidium 86

  10. Basic natural circulation characteristics of SBWR

    International Nuclear Information System (INIS)

    Kuran, S.; Soekmen, C. N.

    2001-01-01

    Natural circulation is an important passive heat removal mechanism for both existing and next generation light water reactors. Simplified Boiling Water Reactor (SBWR) is one of the advanced light water reactors that rely on natural circulation for normal as well as emergency core cooling. In this study, basic natural circulation characteristics of this reactor are examined on a flow loop that simulates the operation of SBWR. On this model, effect of system operating parameters on the steady state natural circulation characteristics inside the loop is studied via solving the transcendental equation for loop flow rate

  11. An update on organohalogen metabolites produced by basidiomycetes

    NARCIS (Netherlands)

    Field, J.A.; Wijnberg, J.B.P.A.

    2003-01-01

    Basidiomycetes are an ecologically important group of higher fungi known for their widespread capacity to produce organohalogen metabolites. To date, 100 different organohalogen metabolites (mostly chlorinated) have been identified from strains in 70 genera of Basidiomycetes. This manuscript

  12. Metabolite coupling in genome-scale metabolic networks

    Directory of Open Access Journals (Sweden)

    Palsson Bernhard Ø

    2006-03-01

    Full Text Available Abstract Background Biochemically detailed stoichiometric matrices have now been reconstructed for various bacteria, yeast, and for the human cardiac mitochondrion based on genomic and proteomic data. These networks have been manually curated based on legacy data and elementally and charge balanced. Comparative analysis of these well curated networks is now possible. Pairs of metabolites often appear together in several network reactions, linking them topologically. This co-occurrence of pairs of metabolites in metabolic reactions is termed herein "metabolite coupling." These metabolite pairs can be directly computed from the stoichiometric matrix, S. Metabolite coupling is derived from the matrix ŜŜT, whose off-diagonal elements indicate the number of reactions in which any two metabolites participate together, where Ŝ is the binary form of S. Results Metabolite coupling in the studied networks was found to be dominated by a relatively small group of highly interacting pairs of metabolites. As would be expected, metabolites with high individual metabolite connectivity also tended to be those with the highest metabolite coupling, as the most connected metabolites couple more often. For metabolite pairs that are not highly coupled, we show that the number of reactions a pair of metabolites shares across a metabolic network closely approximates a line on a log-log scale. We also show that the preferential coupling of two metabolites with each other is spread across the spectrum of metabolites and is not unique to the most connected metabolites. We provide a measure for determining which metabolite pairs couple more often than would be expected based on their individual connectivity in the network and show that these metabolites often derive their principal biological functions from existing in pairs. Thus, analysis of metabolite coupling provides information beyond that which is found from studying the individual connectivity of individual

  13. Studies of the biotransformation and pharmacology of ketamine and its metabolites

    International Nuclear Information System (INIS)

    Leung, Y.

    1986-01-01

    The first part of the research is concerned with the synthesis, resolution and metabolism of norketamine, the primary metabolite of ketamine. Incubations of racemic norketamine, individual enantiomers of norketamine and the pseudoracemates in rat liver microsomes revealed stereoselectivity and enantiomeric interactions during the metabolism of norketamine. The second part of the research describes the synthesis of 6-OH-norketamine, the major secondary metabolite of ketamine, and reports on its pharmacological activity and cerebral distribution in the rat. Primary deuterium isotope effects associated with the metabolism and pharmacological activity of ketamine-N-CD 3 were examined in the third part of this research. The last part of the research deals with the effect of diazepam on the metabolic transformation of ketamine to norketamine in the rat. The fractions of ketamine metabolized to norketamine were found not to be different in the presence or the absence of diazepam

  14. Quantification of brain metabolites in amyotrophic lateral sclerosis by localized proton magnetic resonance spectroscopy

    DEFF Research Database (Denmark)

    Gredal, O; Rosenbaum, S; Topp, S

    1997-01-01

    We performed proton magnetic resonance spectroscopy (1H-MRS) in patients with motor neuron disease (MND) to determine the absolute in vivo concentrations in the brain of the metabolites N-acetyl aspartate (NAA), choline (Cho), and creatine (Cr/PCr). We examined the spectra acquired from a 20 x 20 x...... subjects. We estimated the concentrations of the metabolites using the water signal as an internal standard. The concentrations of Cho and Cr/PCr in both brain regions, as well as the concentration of NAA in the cerebellum, were unaltered in the MND patients compared with the controls. Only MND patients...... with both upper and lower motor neuron signs had a significantly decreased concentration of NAA (9.13 +/- 0.28 mM, mean +/- SEM) in the primary motor cortex when compared with healthy controls (10.03 +/- 0.22 mM). In conclusion, the slightly decreased concentration of NAA in the primary motor cortex from...

  15. Metabolite Depletion Affects Flux Profiling of Cell Lines

    DEFF Research Database (Denmark)

    Nilsson, A.; Haanstra, J. R.; Teusink, B.

    2018-01-01

    Quantifying the rate of consumption and release of metabolites (i.e., flux profiling) has become integral to the study of cancer. The fluxes as well as the growth of the cells may be affected by metabolite depletion during cultivation.......Quantifying the rate of consumption and release of metabolites (i.e., flux profiling) has become integral to the study of cancer. The fluxes as well as the growth of the cells may be affected by metabolite depletion during cultivation....

  16. Main circulator design features for HTR 100, HTR 500 and space heating plants

    International Nuclear Information System (INIS)

    Engel, J.; Glass, D.

    1988-01-01

    All design alternatives for modern high-temperature reactors have a common circulator concept: It is based on a vertical shaft design with a flying impeller. The circulators are equipped with active magnetic bearings and are driven by induction motors connected to variable-speed static converters. Due to their multiple functions during normal reactor operation and under accident conditions, extremely high requirements are made to safety-relevant circulators, since with the reactor pressurized as well as under depressurized conditions specified delivery heads and flow rates have to be ensured. The use of active magnetic bearings permits to obtain maintenance-free operation and functional safety to an extent which had not been achieved before. Magnetic bearings are therefore provided for the total range including primary gas circulators of a drive power of several MW as well as circulators for helium loops of reactor auxiliary systems. The essential feature for using active magnetic bearings is the retainer bearing technology, preventing contact between rotor and static circulator parts upon unintended deenergisation of the magnets. Results of current experiments are reported. Another aspect to be considered for reliable long-term operation for several decades is the effect of rotor dynamics. The various natural frequencies resulting from torsion and bending modes in view of a drive by a frequency-controlled induction motor have to be considered as well as the specific characteristics of the active magnetic bearings. Special attention has to be directed to the internal cooling loop so as to ensure that reactor temperature excursions in the event of deviation from normal operation can be overcome without damage. For circulator components exposed to temperature fields the design characteristics are determined by combining experimental and analytical methods. The coordination of all component parts is currently being optimized on a prototype circulator whose detailed

  17. CIRCULATING MOVING BED COMBUSTION PROOF OF CONCEPT

    Energy Technology Data Exchange (ETDEWEB)

    Jukkola, Glen

    2010-06-30

    Circulating Moving Bed (CMB) combustion technology has its roots in traditional circulating fluidized bed technology and involves a novel method of solid fuel combustion and heat transfer. CMB technology represents a step change in improved performance and cost relative to conventional PC and FBC boilers. The CMB heat exchanger preheats the energy cycle working fluid, steam or air, to the high temperature levels required in systems for advanced power generation. Unique features of the CMB are the reduction of the heat transfer surfaces by about 60% as a result of the enhanced heat transfer rates, flexibility of operation, and about 30% lower cost over existing technology. The CMB Phase I project ran from July 2001 through March 2003. Its objective was to continue development of the CMB technology with a series of proof of concept tests. The tests were conducted at a scale that provided design data for scale up to a demonstration plant. These objectives were met by conducting a series of experiments in ALSTOM Power’s Multi-use Test Facility (MTF). The MTF was modified to operate under CMB conditions of commercial interest. The objective of the tests were to evaluate gas-to-solids heat transfer in the upper furnace, assess agglomeration in the high temperature CMB bubbling bed, and evaluate solids-to-tube heat transfer in the moving bed heat exchanger. The Phase I program results showed that there are still some significant technical uncertainties that needed to be resolved before the technology can be confidently scaled up for a successful demonstration plant design. Work remained in three primary areas: • scale up of gas to solid heat transfer • high temperature finned surface design • the overall requirements of mechanical and process design. The CMB Phase II workscope built upon the results of Phase I and specifically addressed the remaining technical uncertainties. It included a scaled MTF heat transfer test to provide the necessary data to scale up gas

  18. Identifying diseases-related metabolites using random walk.

    Science.gov (United States)

    Hu, Yang; Zhao, Tianyi; Zhang, Ningyi; Zang, Tianyi; Zhang, Jun; Cheng, Liang

    2018-04-11

    Metabolites disrupted by abnormal state of human body are deemed as the effect of diseases. In comparison with the cause of diseases like genes, these markers are easier to be captured for the prevention and diagnosis of metabolic diseases. Currently, a large number of metabolic markers of diseases need to be explored, which drive us to do this work. The existing metabolite-disease associations were extracted from Human Metabolome Database (HMDB) using a text mining tool NCBO annotator as priori knowledge. Next we calculated the similarity of a pair-wise metabolites based on the similarity of disease sets of them. Then, all the similarities of metabolite pairs were utilized for constructing a weighted metabolite association network (WMAN). Subsequently, the network was utilized for predicting novel metabolic markers of diseases using random walk. Totally, 604 metabolites and 228 diseases were extracted from HMDB. From 604 metabolites, 453 metabolites are selected to construct the WMAN, where each metabolite is deemed as a node, and the similarity of two metabolites as the weight of the edge linking them. The performance of the network is validated using the leave one out method. As a result, the high area under the receiver operating characteristic curve (AUC) (0.7048) is achieved. The further case studies for identifying novel metabolites of diabetes mellitus were validated in the recent studies. In this paper, we presented a novel method for prioritizing metabolite-disease pairs. The superior performance validates its reliability for exploring novel metabolic markers of diseases.

  19. 40 CFR 159.179 - Metabolites, degradates, contaminants, and impurities.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 23 2010-07-01 2010-07-01 false Metabolites, degradates, contaminants.../Benefit Information § 159.179 Metabolites, degradates, contaminants, and impurities. (a) Metabolites and... degradation of less than 10 percent in a 30-day period. (b) Contaminants and impurities. The presence in any...

  20. SPE-NMR metabolite sub-profiling of urine

    NARCIS (Netherlands)

    Jacobs, D.M.; Spiesser, L.; Garnier, M.; Roo, de N.; Dorsten, van F.; Hollebrands, B.; Velzen, van E.; Draijer, R.; Duynhoven, van J.P.M.

    2012-01-01

    NMR-based metabolite profiling of urine is a fast and reproducible method for detection of numerous metabolites with diverse chemical properties. However, signal overlap in the (1)H NMR profiles of human urine may hamper quantification and identification of metabolites. Therefore, a new method has

  1. Natural circulation in reactor coolant system

    International Nuclear Information System (INIS)

    Han, J.T.

    1987-01-01

    Reactor coolant system (RCS) natural circulation in a PWR is the buoyancy-driven coolant circulation between the core and the upper-plenum region (in-vessel circulation) with or without a countercurrent flow in the hot leg piping between the vessel and steam generators (ex-vessel circulation). This kind of multidimensional bouyancy-driven flow circulation serves as a means of transferring the heat from the core to the structures in the upper plenum, hot legs, and possibly steam generators. As a result, the RCS piping and other pressure boundaries may be heated to high temperatures at which the structural integrity is challenged. RCS natural circulation is likely to occur during the core uncovery period of the TMLB' accident in a PWR when the vessel upper plenum and hot leg are already drained and filled with steam and possibly other gaseous species. RCS natural circulation is being studied for the Surry plant during the TMLB' accident in which station blackout coincides with the loss of auxiliary feedwater and no operator actions. The effects of the multidimensional RCS natural circulation during the TMLB' accident are discussed

  2. Circulating follistatin in relation to energy metabolism

    DEFF Research Database (Denmark)

    Hansen, Jakob Schiøler; Plomgaard, Peter

    2016-01-01

    a relation to energy metabolism. In this narrative review, we attempt to reconcile the existing findings on circulating follistatin with the novel concept that circulating follistatin is a liver-derived molecule regulated by the glucagon-to-insulin ratio. The picture emerging is that conditions associated...

  3. Identification of fipronil metabolites by time-of-flight mass spectrometry for application in a human exposure study.

    Science.gov (United States)

    McMahen, Rebecca L; Strynar, Mark J; Dagnino, Sonia; Herr, David W; Moser, Virginia C; Garantziotis, Stavros; Andersen, Erik M; Freeborn, Danielle L; McMillan, Larry; Lindstrom, Andrew B

    2015-05-01

    Fipronil is a phenylpyrazole insecticide commonly used in residential and agricultural applications. To understand more about the potential risks for human exposure associated with fipronil, urine and serum from dosed Long Evans adult rats (5 and 10mg/kg bw) were analyzed to identify metabolites as potential biomarkers for use in human biomonitoring studies. Urine from treated rats was found to contain seven unique metabolites, two of which had not been previously reported-M4 and M7 which were putatively identified as a nitroso compound and an imine, respectively. Fipronil sulfone was confirmed to be the primary metabolite in rat serum. The fipronil metabolites identified in the respective matrices were then evaluated in matched human urine (n=84) and serum (n=96) samples from volunteers with no known pesticide exposures. Although no fipronil or metabolites were detected in human urine, fipronil sulfone was present in the serum of approximately 25% of the individuals at concentrations ranging from 0.1 to 4ng/mL. These results indicate that many fipronil metabolites are produced following exposures in rats and that fipronil sulfone is a useful biomarker in human serum. Furthermore, human exposure to fipronil may occur regularly and require more extensive characterization. Published by Elsevier Ltd.

  4. Positive association between concentration of phthalate metabolites in urine and microparticles in adolescents and young adults.

    Science.gov (United States)

    Lin, Chien-Yu; Hsieh, Chia-Jung; Lo, Shyh-Chyi; Chen, Pau-Chung; Torng, Pao-Ling; Hu, Anren; Sung, Fung-Chang; Su, Ta-Chen

    2016-01-01

    Di-(2-ethylhexyl) phthalate (DEHP) has been used worldwide in various products for many years. In vitro studies have shown that exposure to DEHP and its metabolite mono(2-ethylhexyl) phthalate (MEHP) induces endothelial cell apoptosis. Moreover, exposure to DEHP had been linked to cardiovascular risk factors and cardiovascular diseases in epidemiological studies. Circulating microparticles have been known to be indicators of vascular injury. However, whether DEHP or its metabolites are independently associated with microparticles in humans remains unknown. From 2006 to 2008, we recruited 793 subjects (12-30years) from a population-based sample to participate in this cardiovascular disease prevention examination. Each participant was subjected to interviews and biological sample collection to determine the relationship between concentrations of DEHP metabolites MEHP, mono(ethyl-5-hydroxyhexyl) phthalate, and mono(2-ethly-5-oxoheyl) phthalate in urine and concentrations of endothelial microparticles (CD62E and CD31+/CD42a-), platelet microparticles (CD62P and CD31+/CD42a+), and CD14 in serum. Multiple linear regression analysis revealed that an ln-unit increase in MEHP concentration in urine was positively associated with an increase in serum microparticle counts/μL of 0.132 (±0.016) in CD31+/CD42a- (endothelial apoptosis marker), 0.117 (±0.023) in CD31+/CD42a+ (platelet apoptosis marker), and 0.026 (±0.007) in CD14 (monocyte, macrophage, and neutrophil activation marker). There was no association between DEHP metabolite concentration and CD62E or CD62P. In conclusion, a higher MEHP concentration in urine was associated with an increase in endothelial and platelet microparticles in this cohort of adolescents and young adults. Further studies are warranted to clarify the causal relationship between exposure to DEHP and atherosclerosis. Copyright © 2016 Elsevier Ltd. All rights reserved.

  5. Gasification of sawdust in pressurised internally circulating fluidized bed

    Energy Technology Data Exchange (ETDEWEB)

    Maartensson, R.; Lindblom, M. [Lund Univ. (Sweden). Dept. of Chemical Engineering

    1996-12-31

    A test plant for pressurised gasification of biofuels in a internally circulating fluidized bed has been built at the department of Chemical Engineering II at the University of Lund. The design performance is set to maximum 20 bar and 1 050 deg C at a thermal input of 100 kW or a maximum fuel input of 18 kg/in. The primary task is to study pressurised gasification of biofuels in relation to process requirements of the IGCC concept (integrated gasification combined cycle processes), which includes studies in different areas of hot gas clean-up in reducing atmosphere for gas turbine applications. (orig.)

  6. Gasification of sawdust in pressurised internally circulating fluidized bed

    Energy Technology Data Exchange (ETDEWEB)

    Maartensson, R; Lindblom, M [Lund Univ. (Sweden). Dept. of Chemical Engineering

    1997-12-31

    A test plant for pressurised gasification of biofuels in a internally circulating fluidized bed has been built at the department of Chemical Engineering II at the University of Lund. The design performance is set to maximum 20 bar and 1 050 deg C at a thermal input of 100 kW or a maximum fuel input of 18 kg/in. The primary task is to study pressurised gasification of biofuels in relation to process requirements of the IGCC concept (integrated gasification combined cycle processes), which includes studies in different areas of hot gas clean-up in reducing atmosphere for gas turbine applications. (orig.)

  7. Identification of drug metabolites in human plasma or serum integrating metabolite prediction, LC-HRMS and untargeted data processing

    NARCIS (Netherlands)

    Jacobs, P.L.; Ridder, L.; Ruijken, M.; Rosing, H.; Jager, N.G.L.; Beijnen, J.H.; Bas, R.R.; Dongen, W.D. van

    2013-01-01

    Background: Comprehensive identification of human drug metabolites in first-in-man studies is crucial to avoid delays in later stages of drug development. We developed an efficient workflow for systematic identification of human metabolites in plasma or serum that combines metabolite prediction,

  8. Effects of dietary sodium on metabolites: the Dietary Approaches to Stop Hypertension (DASH)-Sodium Feeding Study.

    Science.gov (United States)

    Derkach, Andriy; Sampson, Joshua; Joseph, Justin; Playdon, Mary C; Stolzenberg-Solomon, Rachael Z

    2017-10-01

    Background: High sodium intake is known to increase blood pressure and is difficult to measure in epidemiologic studies. Objective: We examined the effect of sodium intake on metabolites within the DASH (Dietary Approaches to Stop Hypertension Trial)-Sodium Trial to further our understanding of the biological effects of sodium intake beyond blood pressure. Design: The DASH-Sodium Trial randomly assigned individuals to either the DASH diet (low in fat and high in protein, low-fat dairy, and fruits and vegetables) or a control diet for 12 wk. Participants within each diet arm received, in random order, diets containing high (150 nmol or 3450 mg), medium (100 nmol or 2300 mg), and low (50 nmol or 1150 mg) amounts of sodium for 30 d (crossover design). Fasting blood samples were collected at the end of each sodium intervention. We measured 531 identified plasma metabolites in 73 participants at the end of their high- and low-sodium interventions and in 46 participants at the end of their high- and medium-sodium interventions ( N = 119). We used linear mixed-effects regression to model the relation between each log-transformed metabolite and sodium intake. We also combined the resulting P values with Fisher's method to estimate the association between sodium intake and 38 metabolic pathways or groups. Results: Six pathways were associated with sodium intake at a Bonferroni-corrected threshold of 0.0013 (e.g., fatty acid, food component or plant, benzoate, γ-glutamyl amino acid, methionine, and tryptophan). Although 82 metabolites were associated with sodium intake at a false discovery rate ≤0.10, only 4-ethylphenylsufate, a xenobiotic related to benzoate metabolism, was significant at a Bonferroni-corrected threshold ( P Sodium intake is associated with changes in circulating metabolites, including gut microbial, tryptophan, plant component, and γ-glutamyl amino acid-related metabolites. This trial was registered at clinicaltrials.gov as NCT00000608. © 2017

  9. Operating experience with gas-bearing circulators in a high-pressure helium loop

    International Nuclear Information System (INIS)

    Sanders, J.P.; Gat, U.; Young, H.C.

    1988-01-01

    A high-pressure engineering test loop has been designed and constructed at the Oak Ridge National Laboratory for circulating helium through a test chamber at temperatures to 1,000 deg. C. The purpose of this loop is to determine the thermal and structural performance of proposed components for the primary loops of gas-cooled nuclear reactors. Three gas-bearing circulators, mounted in series, provide a maximum volumetric flow of 0.47 m 3 /s and a maximum head of 78 kJ/kg at operating pressures from 0.1 to 10.7 MPa. Control of gaseous impurities in the circulating gas was the significant operating requirement that dictated the choice of a circulator that is lubricated by the circulating gas. The motor for each circulator is contained within the pressure boundary, and it is cooled by circulating the gas in the motor cavity over water-cooled coils. Each motor is rated at 200 kW at a speed of 23,500 rpm. The circulators have been operated in the loop for more than 5,000 h. The flow of the gas in the loop is controlled by varying the speed of the circulators through the use of individual 250-kVA, solid state power supplies that can be continuously varied in frequency from 50 to 400 Hz. To prevent excessive wear on the gas bearings during startup, the circulator motor accelerates the rotor to 3,000 rpm in less than one second. During operation, no problems associated with the gas bearings, per se, were encountered; however, related problems pointed to design considerations that should be included in future applications of circulators of this type. The primary test that has been conducted in this loop required sustained operation for several weeks without interruption. After a number of unscheduled interruptions, the operating goals were attained. During part of this period, the loop was operated with only two circulators installed in the pressure vessels with a guard installed in the third vessel to protect the closure flange from the gas temperatures. Unattended

  10. The neurotoxicity of pyridinium metabolites of haloperidol

    Directory of Open Access Journals (Sweden)

    Agnieszka Górska

    2015-10-01

    Full Text Available Haloperydol is a butyrophenone, typical neuroleptic agent characterized as a high antipsychotics effects in the treatment of schizophrenia and in palliative care to alleviation many syndromes, such as naursea, vomiting and delirium. Clinical problems occurs during and after administration of the drug are side effects, particularly extrapyrramidal symptoms (EPS. The neurotoxicity of haloperydol may be initiated by the cationic metabolites of haloperydol, HPP+, RHPP+, formed by oxidation and reduction pathways. These metabolites are transported by human organic cation transporters (hOCT to several brain structures for exapmle, in substantia nigra, striatum, caudate nucleus, hippocampus. After reaching the dopaminergic neurons inhibits mitochondrial complex I, evidence for free radical involvement, thus leading to neurodegeneration.

  11. Vitamin D metabolites in human milk

    International Nuclear Information System (INIS)

    Weisman, Y.; Bawnik, J.C.; Eisenberg, Z.; Spirer, Z.

    1982-01-01

    The concentrations of unconjugated 25-OHD, 24, 25(OH)2D, and 1,25(OH)2D were measured in human milk by competitive protein-binding radioassays following successive preparative Sephadex LH-20 chromatography and HPLC. The mean (+/- SE) concentration of 25-OHD was 0.37 +/- 0.03 ng/ml, of 24,25(OH)2D was 24.8 +/- 1.9 pg/ml, and of 1,25(OH)2D was 2.2 +/-0.1 pg/ml. The concentration of 25-OHD3 in milk as determined by HPLC and UV detection at 254 nm was 0.27 +/- 0.08 ng/ml. The milk concentrations of vitamin D metabolites did not correlate with the maternal serum 25-OHD levels. The total amounts of unconjugated vitamin D metabolites correspond to the known low bioassayable vitamin D antirachitic activity in human milk

  12. Biologically Active Metabolites Synthesized by Microalgae

    Directory of Open Access Journals (Sweden)

    Michele Greque de Morais

    2015-01-01

    Full Text Available Microalgae are microorganisms that have different morphological, physiological, and genetic traits that confer the ability to produce different biologically active metabolites. Microalgal biotechnology has become a subject of study for various fields, due to the varied bioproducts that can be obtained from these microorganisms. When microalgal cultivation processes are better understood, microalgae can become an environmentally friendly and economically viable source of compounds of interest, because production can be optimized in a controlled culture. The bioactive compounds derived from microalgae have anti-inflammatory, antimicrobial, and antioxidant activities, among others. Furthermore, these microorganisms have the ability to promote health and reduce the risk of the development of degenerative diseases. In this context, the aim of this review is to discuss bioactive metabolites produced by microalgae for possible applications in the life sciences.

  13. Metabolomic analysis of 92 pulmonary embolism patients from a nested case-control study identifies metabolites associated with adverse clinical outcomes.

    Science.gov (United States)

    Zeleznik, O A; Poole, E M; Lindstrom, S; Kraft, P; Van Hylckama Vlieg, A; Lasky-Su, J A; Harrington, L B; Hagan, K; Kim, J; Parry, B A; Giordano, N; Kabrhel, C

    2018-03-01

    Essentials Risk-stratification often fails to predict clinical deterioration in pulmonary embolism (PE). First-ever high-throughput metabolomics analysis of risk-stratified PE patients. Changes in circulating metabolites reflect a compromised energy metabolism in PE. Metabolites play a key role in the pathophysiology and risk stratification of PE. Background Patients with acute pulmonary embolism (PE) exhibit wide variation in clinical presentation and outcomes. Our understanding of the pathophysiologic mechanisms differentiating low-risk and high-risk PE is limited, so current risk-stratification efforts often fail to predict clinical deterioration and are insufficient to guide management. Objectives To improve our understanding of the physiology differentiating low-risk from high-risk PE, we conducted the first-ever high-throughput metabolomics analysis (843 named metabolites) comparing PE patients across risk strata within a nested case-control study. Patients/methods We enrolled 92 patients diagnosed with acute PE and collected plasma within 24 h of PE diagnosis. We used linear regression and pathway analysis to identify metabolites and pathways associated with PE risk-strata. Results When we compared 46 low-risk with 46 intermediate/high-risk PEs, 50 metabolites were significantly different after multiple testing correction. These metabolites were enriched in the following pathways: tricarboxylic acid (TCA) cycle, fatty acid metabolism (acyl carnitine) and purine metabolism, (hypo)xanthine/inosine containing. Additionally, energy, nucleotide and amino acid pathways were downregulated in intermediate/high-risk PE patients. When we compared 28 intermediate-risk with 18 high-risk PE patients, 41 metabolites differed at a nominal P-value level. These metabolites were enriched in fatty acid metabolism (acyl cholines), and hemoglobin and porphyrin metabolism. Conclusion Our results suggest that high-throughput metabolomics can provide insight into the

  14. Role of metabolites of cyclophosphamide in cardiotoxicity

    OpenAIRE

    Kurauchi, Koichiro; Nishikawa, Takuro; Miyahara, Emiko; Okamoto, Yasuhiro; Kawano, Yoshifumi

    2017-01-01

    Background The dose-limiting toxic effect of cyclophosphamide (CY) is cardiotoxicity. The pathogenesis of myocardial damage is poorly understood, and there is no established means of prevention. In previous studies, we suggested that for CY-induced cardiotoxicity, whereas acrolein is the key toxic metabolite, carboxyethylphosphoramide mustard (CEPM) is protective. We sought to verify that acrolein is the main cause of cardiotoxicity and to investigate whether aldehyde dehydrogenase (ALDH), wh...

  15. Fungal Anticancer Metabolites: Synthesis Towards Drug Discovery.

    Science.gov (United States)

    Barbero, Margherita; Artuso, Emma; Prandi, Cristina

    2018-01-01

    Fungi are a well-known and valuable source of compounds of therapeutic relevance, in particular of novel anticancer compounds. Although seldom obtainable through isolation from the natural source, the total organic synthesis still remains one of the most efficient alternatives to resupply them. Furthermore, natural product total synthesis is a valuable tool not only for discovery of new complex biologically active compounds but also for the development of innovative methodologies in enantioselective organic synthesis. We undertook an in-depth literature searching by using chemical bibliographic databases (SciFinder, Reaxys) in order to have a comprehensive insight into the wide research field. The literature has been then screened, refining the obtained results by subject terms focused on both biological activity and innovative synthetic procedures. The literature on fungal metabolites has been recently reviewed and these publications have been used as a base from which we consider the synthetic feasibility of the most promising compounds, in terms of anticancer properties and drug development. In this paper, compounds are classified according to their chemical structure. This review summarizes the anticancer potential of fungal metabolites, highlighting the role of total synthesis outlining the feasibility of innovative synthetic procedures that facilitate the development of fungal metabolites into drugs that may become a real future perspective. To our knowledge, this review is the first effort to deal with the total synthesis of these active fungi metabolites and demonstrates that total chemical synthesis is a fruitful means of yielding fungal derivatives as aided by recent technological and innovative advancements. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  16. New antitumour fungal metabolites from Alternaria porri.

    Science.gov (United States)

    Phuwapraisirisan, Preecha; Rangsan, Jakaphan; Siripong, Pongpan; Tip-Pyang, Santi

    2009-01-01

    Chemical investigation of the onion pathogenic fungus Alternaria porri resulted in the isolation of two new phthalides named zinnimide (2) and deprenylzinnimide (8), along with a new bianthraquinone, alterporriol F (10). The structures of the new metabolites were characterised by spectroscopic analysis and chemical degradation. Of the new compounds isolated, alterporriol F was highly cytotoxic towards HeLa and KB cells, with IC(50) values of 6.5 and 7.0 microg mL(-1).

  17. Moderator circulation in CANDU reactors

    International Nuclear Information System (INIS)

    Fath, H.E.S.; Hussein, M.A.

    1989-01-01

    A two-dimensional computer code that is capable of predicting the moderator flow and temperature distribution inside CANDU calandria is presented. The code uses a new approach to simulate the calandria tube matrix by blocking the cells containing the tubes in the finite difference mesh. A jet momentum-dominant flow pattern is predicted in the nonisothermal case, and the effect of the buoyancy force, resulting from nuclear heating, is found to enhance the speed of circulation. Hot spots are located in low-velocity areas at the top of the calandria and below the inlet jet level between the fuel channels. A parametric study is carried out to investigate the effect of moderator inlet velocity,moderator inlet nozzle location, and geometric scaling. The results indicate that decreasing the moderator inlet velocity has no significant influence on the general features of the flow pattern (i.e., momentum dominant); however, too many high-temperature hot spots appear within the fuel channels

  18. Numerical Modeling of Ocean Circulation

    Science.gov (United States)

    Miller, Robert N.

    2007-01-01

    The modelling of ocean circulation is important not only for its own sake, but also in terms of the prediction of weather patterns and the effects of climate change. This book introduces the basic computational techniques necessary for all models of the ocean and atmosphere, and the conditions they must satisfy. It describes the workings of ocean models, the problems that must be solved in their construction, and how to evaluate computational results. Major emphasis is placed on examining ocean models critically, and determining what they do well and what they do poorly. Numerical analysis is introduced as needed, and exercises are included to illustrate major points. Developed from notes for a course taught in physical oceanography at the College of Oceanic and Atmospheric Sciences at Oregon State University, this book is ideal for graduate students of oceanography, geophysics, climatology and atmospheric science, and researchers in oceanography and atmospheric science. Features examples and critical examination of ocean modelling and results Demonstrates the strengths and weaknesses of different approaches Includes exercises to illustrate major points and supplement mathematical and physical details

  19. Circulating microparticles: square the circle

    Science.gov (United States)

    2013-01-01

    Background The present review summarizes current knowledge about microparticles (MPs) and provides a systematic overview of last 20 years of research on circulating MPs, with particular focus on their clinical relevance. Results MPs are a heterogeneous population of cell-derived vesicles, with sizes ranging between 50 and 1000 nm. MPs are capable of transferring peptides, proteins, lipid components, microRNA, mRNA, and DNA from one cell to another without direct cell-to-cell contact. Growing evidence suggests that MPs present in peripheral blood and body fluids contribute to the development and progression of cancer, and are of pathophysiological relevance for autoimmune, inflammatory, infectious, cardiovascular, hematological, and other diseases. MPs have large diagnostic potential as biomarkers; however, due to current technological limitations in purification of MPs and an absence of standardized methods of MP detection, challenges remain in validating the potential of MPs as a non-invasive and early diagnostic platform. Conclusions Improvements in the effective deciphering of MP molecular signatures will be critical not only for diagnostics, but also for the evaluation of treatment regimens and predicting disease outcomes. PMID:23607880

  20. Vertical mixing by Langmuir circulations

    International Nuclear Information System (INIS)

    McWilliams, James C.; Sullivan, Peter P.

    2001-01-01

    Wind and surface wave frequently induce Langmuir circulations (LC) in the upper ocean, and the LC contribute to mixing materials down from the surface. In this paper we analyze large-eddy simulation (LES) cases based on surface-wave-averaged, dynamical equations and show that the effect of the LC is a great increase in the vertical mixing efficiency for both material properties and momentum. We provide new confirmation that the previously proposed K-profile parameterization (KPP) model accurately characterizes the turbulent transport in a weakly convective, wind-driven boundary layer with stable interior stratification. We also propose a modest generalization of KPP for the regime of weakly convective Langmuir turbulence. This makes the KPP turbulent flux profiles match those in the LES case with LC present fairly well, especially so for material properties being transported downwards from the ocean surface. However, some open issues remain about how well the present LES and KPP formulations represent Langmuir turbulence, in part because wave-breaking effects are not yet included. (Author)

  1. Phthalate Metabolites, Consumer Habits and Health Effects

    Directory of Open Access Journals (Sweden)

    Peter Wallner

    2016-07-01

    Full Text Available Phthalates are multifunctional chemicals used in a wide variety of consumer products. The aim of this study was to investigate whether levels of urinary phthalate metabolites in urine samples of Austrian mothers and their children were associated with consumer habits and health indicators. Within an Austrian biomonitoring survey, urine samples from 50 mother-child pairs of five communities (two-stage random stratified sampling were analysed. The concentrations of 14 phthalate metabolites were determined, and a questionnaire was administered. Monoethyl phthalate (MEP, mono-n-butyl phthalate (MnBP, mono-isobutyl phthalate (MiBP, monobenzyl phthalate (MBzP, mono-(2-ethylhexyl phthalate (MEHP, mono-(2-ethyl-5-hydroxyhexyl phthalate (5OH-MEHP, mono-(2-ethyl-5-oxohexyl phthalate (5oxo-MEHP, mono-(5-carboxy-2-ethylpentyl phthalate (5cx-MEPP, and 3-carboxy-mono-propyl phthalate (3cx-MPP could be quantified in the majority of samples. Significant correlations were found between the use of hair mousse, hair dye, makeup, chewing gum, polyethylene terephthalate (PET bottles and the diethyl phthalate (DEP metabolite MEP. With regard to health effects, significant associations of MEP in urine with headache, repeated coughing, diarrhoea, and hormonal problems were observed. MBzP was associated with repeated coughing and MEHP was associated with itching.

  2. Natural metabolites for parasitic weed management.

    Science.gov (United States)

    Vurro, Maurizio; Boari, Angela; Evidente, Antonio; Andolfi, Anna; Zermane, Nadjia

    2009-05-01

    Compounds of natural origin, such as phytotoxins produced by fungi or natural amino acids, could be used in parasitic weed management strategies by interfering with the early growth stages of the parasites. These metabolites could inhibit seed germination or germ tube elongation, so preventing attachment to the host plant, or, conversely, stimulate seed germination in the absence of the host, contributing to a reduction in the parasite seed bank. Some of the fungal metabolites assayed were very active even at very low concentrations, such as some macrocyclic trichothecenes, which at 0.1 microM strongly suppressed the germination of Orobanche ramosa L. seeds. Interesting results were also obtained with some novel toxins, such as phyllostictine A, highly active in reducing germ tube elongation and seed germination both of O. ramosa and of Cuscuta campestris Yuncker. Among the amino acids tested, methionine and arginine were particularly interesting, as they were able to suppress seed germination at concentrations lower than 1 mM. Some of the fungal metabolites tested were also able to stimulate the germination of O. ramosa seeds. The major findings in this research field are described and discussed.

  3. Phthalate Metabolites, Consumer Habits and Health Effects.

    Science.gov (United States)

    Wallner, Peter; Kundi, Michael; Hohenblum, Philipp; Scharf, Sigrid; Hutter, Hans-Peter

    2016-07-15

    Phthalates are multifunctional chemicals used in a wide variety of consumer products. The aim of this study was to investigate whether levels of urinary phthalate metabolites in urine samples of Austrian mothers and their children were associated with consumer habits and health indicators. Within an Austrian biomonitoring survey, urine samples from 50 mother-child pairs of five communities (two-stage random stratified sampling) were analysed. The concentrations of 14 phthalate metabolites were determined, and a questionnaire was administered. Monoethyl phthalate (MEP), mono-n-butyl phthalate (MnBP), mono-isobutyl phthalate (MiBP), monobenzyl phthalate (MBzP), mono-(2-ethylhexyl) phthalate (MEHP), mono-(2-ethyl-5-hydroxyhexyl) phthalate (5OH-MEHP), mono-(2-ethyl-5-oxohexyl) phthalate (5oxo-MEHP), mono-(5-carboxy-2-ethylpentyl) phthalate (5cx-MEPP), and 3-carboxy-mono-propyl phthalate (3cx-MPP) could be quantified in the majority of samples. Significant correlations were found between the use of hair mousse, hair dye, makeup, chewing gum, polyethylene terephthalate (PET) bottles and the diethyl phthalate (DEP) metabolite MEP. With regard to health effects, significant associations of MEP in urine with headache, repeated coughing, diarrhoea, and hormonal problems were observed. MBzP was associated with repeated coughing and MEHP was associated with itching.

  4. Metabolite profiling of Alzheimer's disease cerebrospinal fluid.

    Directory of Open Access Journals (Sweden)

    Christian Czech

    Full Text Available Alzheimer's disease (AD is a neurodegenerative disorder characterized by progressive loss of cognitive functions. Today the diagnosis of AD relies on clinical evaluations and is only late in the disease. Biomarkers for early detection of the underlying neuropathological changes are still lacking and the biochemical pathways leading to the disease are still not completely understood. The aim of this study was to identify the metabolic changes resulting from the disease phenotype by a thorough and systematic metabolite profiling approach. For this purpose CSF samples from 79 AD patients and 51 healthy controls were analyzed by gas and liquid chromatography-tandem mass spectrometry (GC-MS and LC-MS/MS in conjunction with univariate and multivariate statistical analyses. In total 343 different analytes have been identified. Significant changes in the metabolite profile of AD patients compared to healthy controls have been identified. Increased cortisol levels seemed to be related to the progression of AD and have been detected in more severe forms of AD. Increased cysteine associated with decreased uridine was the best paired combination to identify light AD (MMSE>22 with specificity and sensitivity above 75%. In this group of patients, sensitivity and specificity above 80% were obtained for several combinations of three to five metabolites, including cortisol and various amino acids, in addition to cysteine and uridine.

  5. Analysis of Intracellular Metabolites from Microorganisms: Quenching and Extraction Protocols.

    Science.gov (United States)

    Pinu, Farhana R; Villas-Boas, Silas G; Aggio, Raphael

    2017-10-23

    Sample preparation is one of the most important steps in metabolome analysis. The challenges of determining microbial metabolome have been well discussed within the research community and many improvements have already been achieved in last decade. The analysis of intracellular metabolites is particularly challenging. Environmental perturbations may considerably affect microbial metabolism, which results in intracellular metabolites being rapidly degraded or metabolized by enzymatic reactions. Therefore, quenching or the complete stop of cell metabolism is a pre-requisite for accurate intracellular metabolite analysis. After quenching, metabolites need to be extracted from the intracellular compartment. The choice of the most suitable metabolite extraction method/s is another crucial step. The literature indicates that specific classes of metabolites are better extracted by different extraction protocols. In this review, we discuss the technical aspects and advancements of quenching and extraction of intracellular metabolite analysis from microbial cells.

  6. Analysis of Intracellular Metabolites from Microorganisms: Quenching and Extraction Protocols

    Directory of Open Access Journals (Sweden)

    Farhana R. Pinu

    2017-10-01

    Full Text Available Sample preparation is one of the most important steps in metabolome analysis. The challenges of determining microbial metabolome have been well discussed within the research community and many improvements have already been achieved in last decade. The analysis of intracellular metabolites is particularly challenging. Environmental perturbations may considerably affect microbial metabolism, which results in intracellular metabolites being rapidly degraded or metabolized by enzymatic reactions. Therefore, quenching or the complete stop of cell metabolism is a pre-requisite for accurate intracellular metabolite analysis. After quenching, metabolites need to be extracted from the intracellular compartment. The choice of the most suitable metabolite extraction method/s is another crucial step. The literature indicates that specific classes of metabolites are better extracted by different extraction protocols. In this review, we discuss the technical aspects and advancements of quenching and extraction of intracellular metabolite analysis from microbial cells.

  7. 46 CFR 56.50-45 - Circulating pumps.

    Science.gov (United States)

    2010-10-01

    ... APPURTENANCES Design Requirements Pertaining to Specific Systems § 56.50-45 Circulating pumps. (a) A main circulating pump and emergency means for circulating water through the main condenser shall be provided. The... circulating pump and the condenser. (b) Independent sea suctions shall be provided for the main circulating...

  8. Primary explosives

    Energy Technology Data Exchange (ETDEWEB)

    Matyas, Robert; Pachman, Jiri [Pardubice Univ. (Czech Republic). Faculty of Chemical Technology

    2013-06-01

    The first chapter provides background such as the basics of initiation and differences between requirements on primary explosives used in detonators and igniters. The authors then clarify the influence of physical characteristics on explosive properties, focusing on those properties required for primary explosives. Furthermore, the issue of sensitivity is discussed. All the chapters on particular groups of primary explosives are structured in the same way, including introduction, physical and chemical properties, explosive properties, preparation and documented use.

  9. Primary fibromyalgia

    DEFF Research Database (Denmark)

    Jacobsen, S; Jensen, L T; Foldager, M

    1990-01-01

    Serum concentrations of procollagen type III aminoterminal peptide have previously been reported to be low in some patients with primary fibromyalgia and the aim of this study was to determine if such patients differ clinically from primary fibromyalgia patients with normal levels of procollagen...... type III aminoterminal peptide. Subjective symptoms, tender points and dynamic muscle strength in 45 women with primary fibromyalgia were related to serum concentrations of procollagen type III aminoterminal peptide. Patients with low serum concentrations of procollagen type III aminoterminal peptide...... concentrations of procollagen type III aminoterminal peptide of primary fibromyalgia patients are connected to the disease impact....

  10. MeRy-B, a metabolomic database and knowledge base for exploring plant primary metabolism.

    Science.gov (United States)

    Deborde, Catherine; Jacob, Daniel

    2014-01-01

    Plant primary metabolites are organic compounds that are common to all or most plant species and are essential for plant growth, development, and reproduction. They are intermediates and products of metabolism involved in photosynthesis and other biosynthetic processes. Primary metabolites belong to different compound families, mainly carbohydrates, organic acids, amino acids, nucleotides, fatty acids, steroids, or lipids. Until recently, unlike the Human Metabolome Database ( http://www.hmdb.ca ) dedicated to human metabolism, there was no centralized database or repository dedicated exclusively to the plant kingdom that contained information on metabolites and their concentrations in a detailed experimental context. MeRy-B is the first platform for plant (1)H-NMR metabolomic profiles (MeRy-B, http://bit.ly/meryb ), designed to provide a knowledge base of curated plant profiles and metabolites obtained by NMR, together with the corresponding experimental and analytical metadata. MeRy-B contains lists of plant metabolites, mostly primary metabolites and unknown compounds, with information about experimental conditions, the factors studied, and metabolite concentrations for 19 different plant species (Arabidopsis, broccoli, daphne, grape, maize, barrel clover, melon, Ostreococcus tauri, palm date, palm tree, peach, pine tree, eucalyptus, plantain rice, strawberry, sugar beet, tomato, vanilla), compiled from more than 2,300 annotated NMR profiles for various organs or tissues deposited by 30 different private or public contributors in September 2013. Currently, about half of the data deposited in MeRy-B is publicly available. In this chapter, readers will be shown how to (1) navigate through and retrieve data of publicly available projects on MeRy-B website; (2) visualize lists of experimentally identified metabolites and their concentrations in all plant species present in MeRy-B; (3) get primary metabolite list for a particular plant species in MeRy-B; and for a

  11. Preliminary test results and CFD analysis for moderator circulation test at Korea

    Energy Technology Data Exchange (ETDEWEB)

    Kim, H.T. [Korea Atomic Energy Research Inst., Daejeon (Korea, Republic of); Im, S.H.; Sung, H.J. [Korea Advanced Inst. of Science and Tech., Daejeon (Korea, Republic of); Seo, H.; Bang, I.C. [Ulsan National Inst. of Science and Tech., Ulsan (Korea, Republic of)

    2014-07-01

    Korea Atomic Energy Research Institute (KAERI) is carrying out a scaled-down moderator test program to simulate the CANDU6 moderator circulation phenomena during steady state operation and accident conditions. This research program includes the construction of the Moderator Circulation Test (MCT) facility, production of the validation data for self-reliant CFD tools, and development of optical measurement system using the Particle Image Velocimetry (PIV). The MCT facility includes a primary circulation loop (pipe lines, a primary side pump, a heat exchanger, valves, flow meters) and a secondary side loop (pipe lines, a secondary side pump, and an external cooling tower). The loop leakage test and non-heating test are performed in the present work. In the present work the PIV technique is used to measure the velocity distributions in the scaled moderator tank of MCT under iso-thermal test conditions. The preliminary PIV measurement data are obtained and compared with CFX code predictions. (author)

  12. Preliminary test results and CFD analysis for moderator circulation test at Korea

    International Nuclear Information System (INIS)

    Kim, H.T.; Im, S.H.; Sung, H.J.; Seo, H.; Bang, I.C.

    2014-01-01

    Korea Atomic Energy Research Institute (KAERI) is carrying out a scaled-down moderator test program to simulate the CANDU6 moderator circulation phenomena during steady state operation and accident conditions. This research program includes the construction of the Moderator Circulation Test (MCT) facility, production of the validation data for self-reliant CFD tools, and development of optical measurement system using the Particle Image Velocimetry (PIV). The MCT facility includes a primary circulation loop (pipe lines, a primary side pump, a heat exchanger, valves, flow meters) and a secondary side loop (pipe lines, a secondary side pump, and an external cooling tower). The loop leakage test and non-heating test are performed in the present work. In the present work the PIV technique is used to measure the velocity distributions in the scaled moderator tank of MCT under iso-thermal test conditions. The preliminary PIV measurement data are obtained and compared with CFX code predictions. (author)

  13. Vibration features of an 180 kW maglev circulator test rig

    International Nuclear Information System (INIS)

    Su Jiageng; Li Hongwei; Shi Qian; Sha Honglei; Yu Suyuan

    2015-01-01

    The helium circulator is the key equipment to drive the helium gas flowing in the primary loop for energy exchange in HTGR. Active magnetic bearings (AMB) have been considered as an alternative to replace traditional mechanical bearings in the helium circulator. Such contactless bearings do not have frictional wear and can be used to suppress vibration in rotor-dynamic applications. It is necessary to study the vibration characteristics of the maglev helium circulator to guarantee the reactor safety. Therefore, a maglev circulator test rig was built. The power of the circulator is 180 kW and the maximum speed is 17000 rpm. For the time being, the test atmosphere is air. In this paper the test rig was introduced. Vibration test work of the maglev circulator was also carried out. The measuring points were arranged at the seat because the seat vibration level is important to evaluate the machine noise. The measuring points were also arranged at the base of the circulator housing to better study the vibration characteristics. The vibrations were measured by the LC-8024 multichannel machinery diagnoses system. At each measuring point the vibrations were detected in three directions (X, Y and Z) with the vibration acceleration sensors. The test speeds varied from 1000 rpm to 17000 rpm with an increase of 1000 rpm each time. The vibration values of the seat are from 89.5 dB at 1000 rpm to 113.3 dB at 17000 rpm. The test results showed that the maglev circulator exhibits good vibration properties. This work will offer important theoretical base and engineering experience to explore the high-speed helium circulator in HTGR. (author)

  14. Development of CO2 circulators

    International Nuclear Information System (INIS)

    Donaldson, J.

    1988-01-01

    The development of the basic machine types we have supplied has not been without problems. The Windscale AGR (the prototype AGR) was a small 1.2 MW vertically up circulator with an inlet temperature of 237 deg. C (459 deg. F). Oil leakage problems occurred and were cured in the works test facility and the machine went into service with no other problems. The Horizontal 5 MW machines for Hinkley/Hunterston were not so fortunate with vibration problems, interface corrosion problems (effecting the whole reactor) and material dimensional stability problems. Oil ingress problems did not show up in test work but were later reported from site. These reports were initially exagerated due to the measuring techniques which took the operators some time to resolve. In the vertical 5 MW machines for Hartlepool and Heysham 1 there are two interesting factors, firstly a spar failure and secondly shaft axial stability. Many of the problems were due to modifications at site or our inability to model all aspects of site installation from which lessons for the future can be learned. The latest stations Torness and Heysham II incorporate these lessons. The machines have been designed with so much margin that during the resolution of the reactor control rod gag problems the machines were run continuously at 20% overload (6.3 MW). From an initial accident case of 350 deg. C inlet temperature, this increased to 458 deg. C and now stands at 585 deg. C. No modifications to the impeller were required. The site experience to date is good with no operational problems reported. (author). 4 figs

  15. SpaceX Dragon Air Circulation System

    Science.gov (United States)

    Hernandez, Brenda; Piatrovich, Siarhei; Prina, Mauro

    2011-01-01

    The Dragon capsule is a reusable vehicle being developed by Space Exploration Technologies (SpaceX) that will provide commercial cargo transportation to the International Space Station (ISS). Dragon is designed to be a habitable module while it is berthed to ISS. As such, the Dragon Environmental Control System (ECS) consists of pressure control and pressure equalization, air sampling, fire detection, illumination, and an air circulation system. The air circulation system prevents pockets of stagnant air in Dragon that can be hazardous to the ISS crew. In addition, through the inter-module duct, the air circulation system provides fresh air from ISS into Dragon. To utilize the maximum volume of Dragon for cargo packaging, the Dragon ECS air circulation system is designed around cargo rack optimization. At the same time, the air circulation system is designed to meet the National Aeronautics Space Administration (NASA) inter-module and intra-module ventilation requirements and acoustic requirements. A flight like configuration of the Dragon capsule including the air circulation system was recently assembled for testing to assess the design for inter-module and intra-module ventilation and acoustics. The testing included the Dragon capsule, and flight configuration in the pressure section with cargo racks, lockers, all of the air circulation components, and acoustic treatment. The air circulation test was also used to verify the Computational Fluid Dynamics (CFD) model of the Dragon capsule. The CFD model included the same Dragon internal geometry that was assembled for the test. This paper will describe the Dragon air circulation system design which has been verified by testing the system and with CFD analysis.

  16. New Methodology for Known Metabolite Identification in Metabonomics/Metabolomics: Topological Metabolite Identification Carbon Efficiency (tMICE).

    Science.gov (United States)

    Sanchon-Lopez, Beatriz; Everett, Jeremy R

    2016-09-02

    A new, simple-to-implement and quantitative approach to assessing the confidence in NMR-based identification of known metabolites is introduced. The approach is based on a topological analysis of metabolite identification information available from NMR spectroscopy studies and is a development of the metabolite identification carbon efficiency (MICE) method. New topological metabolite identification indices are introduced, analyzed, and proposed for general use, including topological metabolite identification carbon efficiency (tMICE). Because known metabolite identification is one of the key bottlenecks in either NMR-spectroscopy- or mass spectrometry-based metabonomics/metabolomics studies, and given the fact that there is no current consensus on how to assess metabolite identification confidence, it is hoped that these new approaches and the topological indices will find utility.

  17. Circulating microRNAs in breast cancer

    DEFF Research Database (Denmark)

    Hamam, Rimi; Hamam, Dana; Alsaleh, Khalid A.

    2017-01-01

    Effective management of breast cancer depends on early diagnosis and proper monitoring of patients' response to therapy. However, these goals are difficult to achieve because of the lack of sensitive and specific biomarkers for early detection and for disease monitoring. Accumulating evidence...... in the past several years has highlighted the potential use of peripheral blood circulating nucleic acids such as DNA, mRNA and micro (mi)RNA in breast cancer diagnosis, prognosis and for monitoring response to anticancer therapy. Among these, circulating miRNA is increasingly recognized as a promising...... circulating miRNAs as diagnostic, prognostic or predictive biomarkers in breast cancer management....

  18. Embolization of Cyanoacrylate glue in systemic circulation in a case of hepatocellular carcinoma: an autopsy report

    Directory of Open Access Journals (Sweden)

    Kochhar Rakesh K

    2009-12-01

    Full Text Available Abstract We report a case of embolism of the sclerosant dye with subsequent formation of foreign-body giant cell reaction within the veins of pulmonary and portal circulation in an autopsy case of hepatocellular carcinoma developing over an underlying primary biliary cirrhosis.

  19. Effects of caffeine, tea polyphenol and daidzein on the pharmacokinetics of lansoprazole and its metabolites in rats

    OpenAIRE

    Wu, Tao; Wu, Ji; Gao, Ping; Xiang, Daochun; Liu, Dong; Song, Hongping

    2015-01-01

    abstract The aim of this study was to evaluate the effects of caffeine, tea polyphenol and daidzein on the pharmacokinetics of lansoprazole and its metabolites. Rats were intragastrically administered caffeine (30 mg·kg-1, once per day), tea polyphenol (400 mg·kg-1, once per day) or daidzein (13.5 mg·kg-1, once per day) for 14 days, followed by an intragastric administration of lansoprazole (8 mg·kg-1) on the 15th day. The plasma concentrations of lansoprazole and its two primary metabolites,...

  20. Trophic transfer of pyrene metabolites between aquatic invertebrates

    International Nuclear Information System (INIS)

    Carrasco Navarro, V.; Leppänen, M.T.; Kukkonen, J.V.K.; Godoy Olmos, S.

    2013-01-01

    The trophic transfer of pyrene metabolites was studied using Gammarus setosus as a predator and the invertebrates Lumbriculus variegatus and Chironomus riparius as prey. The results obtained by liquid scintillation counting confirmed that the pyrene metabolites produced by the aquatic invertebrates L. variegatus and C. riparius were transferred to G. setosus through the diet. More detailed analyses by liquid chromatography discovered that two of the metabolites produced by C. riparius appeared in the chromatograms of G. setosus tissue extracts, proving their trophic transfer. These metabolites were not present in chromatograms of G. setosus exclusively exposed to pyrene. The present study supports the trophic transfer of PAH metabolites between benthic macroinvertebrates and common species of an arctic amphipod. As some PAH metabolites are more toxic than the parent compounds, the present study raises concerns about the consequences of their trophic transfer and the fate and effects of PAHs in natural environments. - Highlights: ► The trophic transfer of pyrene metabolites between invertebrates was evaluated. ► Biotransformation of pyrene by L. variegatus and C. riparius is different. ► Metabolites produced by L. variegatus and C. riparius are transferred to G. setosus. ► Specifically, two metabolites produced by C. riparius were transferred. - Some of the pyrene metabolites produced by the model invertebrates L. variegatus and C. riparius are transferred to G. setosus through the diet, proving their trophic transfer.

  1. Metabolite damage and repair in metabolic engineering design.

    Science.gov (United States)

    Sun, Jiayi; Jeffryes, James G; Henry, Christopher S; Bruner, Steven D; Hanson, Andrew D

    2017-11-01

    The necessarily sharp focus of metabolic engineering and metabolic synthetic biology on pathways and their fluxes has tended to divert attention from the damaging enzymatic and chemical side-reactions that pathway metabolites can undergo. Although historically overlooked and underappreciated, such metabolite damage reactions are now known to occur throughout metabolism and to generate (formerly enigmatic) peaks detected in metabolomics datasets. It is also now known that metabolite damage is often countered by dedicated repair enzymes that undo or prevent it. Metabolite damage and repair are highly relevant to engineered pathway design: metabolite damage reactions can reduce flux rates and product yields, and repair enzymes can provide robust, host-independent solutions. Herein, after introducing the core principles of metabolite damage and repair, we use case histories to document how damage and repair processes affect efficient operation of engineered pathways - particularly those that are heterologous, non-natural, or cell-free. We then review how metabolite damage reactions can be predicted, how repair reactions can be prospected, and how metabolite damage and repair can be built into genome-scale metabolic models. Lastly, we propose a versatile 'plug and play' set of well-characterized metabolite repair enzymes to solve metabolite damage problems known or likely to occur in metabolic engineering and synthetic biology projects. Copyright © 2017 International Metabolic Engineering Society. All rights reserved.

  2. Metabolite damage and repair in metabolic engineering design

    Energy Technology Data Exchange (ETDEWEB)

    Sun, Jiayi; Jeffryes, James G.; Henry, Christopher S.; Bruner, Steven D.; Hanson, Andrew D.

    2017-11-01

    The necessarily sharp focus of metabolic engineering and metabolic synthetic biology on pathways and their fluxes has tended to divert attention from the damaging enzymatic and chemical side-reactions that pathway metabolites can undergo. Although historically overlooked and underappreciated, such metabolite damage reactions are now known to occur throughout metabolism and to generate (formerly enigmatic) peaks detected in metabolomics datasets. It is also now known that metabolite damage is often countered by dedicated repair enzymes that undo or prevent it. Metabolite damage and repair are highly relevant to engineered pathway design: metabolite damage reactions can reduce flux rates and product yields, and repair enzymes can provide robust, host-independent solutions. Herein, after introducing the core principles of metabolite damage and repair, we use case histories to document how damage and repair processes affect efficient operation of engineered pathways - particularly those that are heterologous, non-natural, or cell-free. We then review how metabolite damage reactions can be predicted, how repair reactions can be prospected, and how metabolite damage and repair can be built into genome-scale metabolic models. Lastly, we propose a versatile 'plug and play' set of well-characterized metabolite repair enzymes to solve metabolite damage problems known or likely to occur in metabolic engineering and synthetic biology projects.

  3. The urinary metabolites of DINCH® have an impact on the activities of the human nuclear receptors ERα, ERβ, AR, PPARα and PPARγ.

    Science.gov (United States)

    Engel, Anika; Buhrke, Thorsten; Kasper, Stefanie; Behr, Anne-Cathrin; Braeuning, Albert; Jessel, Sönke; Seidel, Albrecht; Völkel, Wolfgang; Lampen, Alfonso

    2018-05-01

    DINCH ® (di-isononyl cyclohexane-1,2-dicarboxylate) is a non-phthalate plasticizer that has been developed to replace phthalate plasticizers such as DEHP (di-2-ethylhexyl phthalate) or DINP (di-isononyl phthalate). DINCH ® is metabolized to its corresponding monoester and subsequently to oxidized monoester derivatives. These are conjugated to glucuronic acid and subject to urinary excretion. In contrast to DINCH ® , there are almost no toxicological data available regarding its primary and secondary metabolites. The present study aimed at the characterization of potential endocrine properties of DINCH ® and five DINCH ® metabolites by using reporter gene assays to monitor the activity of the human nuclear receptors ERα, ERβ, AR, PPARα and PPARγ in vitro. DINCH ® itself did not have any effect on the activity of these receptors whereas DINCH ® metabolites were shown to activate all these receptors. In the case of AR, DINCH ® metabolites predominantly enhanced dihydrotestosterone-stimulated AR activity. In the H295R steroidogenesis assay, neither DINCH ® nor any of its metabolites affected estradiol or testosterone synthesis. In conclusion, primary and secondary DINCH ® metabolites exert different effects at the molecular level compared to DINCH ® itself. All these in vitro effects of DINCH ® metabolites, however, were only observed at high concentrations such as 10 μM or above which is about three orders of magnitude above reported DINCH ® metabolite concentrations in human urine. Thus, the in vitro data do not support the notion that DINCH ® or any of the investigated metabolites may exert considerable endocrine effects in vivo at relevant human exposure levels. Copyright © 2018 Elsevier B.V. All rights reserved.

  4. Potential antiproliferative activity of polyphenol metabolites against human breast cancer cells and their urine excretion pattern in healthy subjects following acute intake of a polyphenol-rich juice of grumixama (Eugenia brasiliensis Lam.).

    Science.gov (United States)

    Teixeira, L L; Costa, G R; Dörr, F A; Ong, T P; Pinto, E; Lajolo, F M; Hassimotto, N M A

    2017-06-21

    The bioavailability and metabolism of anthocyanins and ellagitannins following acute intake of grumixama fruit, native Brazilian cherry, by humans, and its in vitro antiproliferative activity against breast cancer cells (MDA-MB-231) were investigated. A single dose of grumixama juice was administered to healthy women (n = 10) and polyphenol metabolites were analyzed in urine and plasma samples collected over 24 h. The majority of the metabolites circulating and excreted in urine were phenolic acids and urolithin conjugates, the gut microbiota catabolites of both classes of polyphenols, respectively. According to pharmacokinetic parameters, the subjects were divided into two distinct groups, high and low urinary metabolite excretors. The pool of polyphenol metabolites found in urine samples showed a significant inhibition of cell proliferation and G2/M cell cycle arrest in MDA-MB-231 cells. Our findings demonstrate the large interindividual variability concerning the polyphenol metabolism, which possibly could reflect in health promotion.

  5. Metabolites related to renal function, immune activation, and carbamylation are associated with muscle composition in older adults.

    Science.gov (United States)

    Lustgarten, Michael S; Fielding, Roger A

    2017-12-15

    Reduced skeletal muscle density in older adults is associated with insulin resistance, decreased physical function, and an increased all-cause mortality risk. To elucidate mechanisms that may underlie the maintenance of skeletal muscle density, we conducted a secondary analysis of previously published muscle composition and serum metabolomic data in 73 older adults (average age, 78y). Multivariable-adjusted linear regression was used to examine associations between 321 metabolites with muscle composition, defined as the ratio between normal density (NDM) with low density (LDM) thigh muscle cross sectional area (NDM/LDM). Sixty metabolites were significantly (p≤0.05 and qMetabolites that were significantly associated with muscle composition were then tested for their association with circulating markers of renal function (blood urea nitrogen, creatinine, uric acid), and with the immune response (neutrophils/lymphocytes) and activation (kynurenine/tryptophan). 43 significant NDM/LDM metabolites (including urea) were co-associated with at least 1 marker of renal function; 23 of these metabolites have been previously identified as uremic solutes. The neutrophil/lymphocyte ratio was significantly associated with NDM/LDM (β±SE: -0.3±0.1, p=0.01, q=0.04). 35 significant NDM/LDM metabolites were co-associated with immune activation. Carbamylation (defined as homocitrulline/lysine) was identified as a pathway that may link renal function and immune activation with muscle composition, as 29 significant NDM/LDM metabolites were co-associated with homocitrulline/lysine, with at least 2 markers of renal function, and with kynurenine/tryptophan. When considering that elevated urea and uremic metabolites have been linked with an increased systemic microbial burden, that antimicrobial defense can be reduced in the presence of carbamylation, and that adipocytes can promote host defense, we propose the novel hypothesis that the age-related increase in adipogenesis within muscle

  6. Characterization of fluidization regime in circulating fluidized bed reactor with high solid particle concentration using computational fluid dynamics

    Energy Technology Data Exchange (ETDEWEB)

    Chalermsinsuwan, Benjapon; Thummakul, Theeranan; Piumsomboon, Pornpote [Chulalongkorn University, Bangkok (Thailand); Gidaspow, Dimitri [Armour College of Engineering, Chicago (United States)

    2014-02-15

    The hydrodynamics inside a high solid particle concentration circulating fluidized bed reactor was investigated using computational fluid dynamics simulation. Compared to a low solid particle reactor, all the conventional fluidization regimes were observed. In addition, two unconventional fluidization regimes, circulating-turbulent and dense suspension bypassing regimes, were found with only primary gas injection. The circulating-turbulent fluidization regime showed uniformly dense solid particle distribution in all the system directions, while the dense suspension bypassing fluidization regime exhibited the flow of solid particles at only one side system wall. Then, comprehensive fluidization regime clarification and mapping were evaluated using in-depth system parameters. In the circulating-turbulent fluidization regime, the total granular temperature was low compared to the adjacent fluidization regimes. In the dense suspension bypassing fluidization regime, the highest total granular temperature was obtained. The circulating-turbulent and dense suspension bypassing fluidization regimes are suitable for sorption and transportation applications, respectively.

  7. Seawater circulating system in an aquaculture laboratory

    Digital Repository Service at National Institute of Oceanography (India)

    Chatterji, A.; Ingole, B.S.; Parulekar, A.H.

    The note gives an account, for the first time in India, of an Aquaculture Laboratory with open type seawater circulating system developed at the National Institute of Oceanography, Goa, India. Besides describing the details of the system...

  8. EOP MIT General Circulation Model (MITgcm)

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — This data contains a regional implementation of the Massachusetts Institute of Technology general circulation model (MITgcm) at a 1-km spatial resolution for the...

  9. Seasonal Overturning Circulation in the Red Sea

    Science.gov (United States)

    Yao, F.; Hoteit, I.; Koehl, A.

    2010-12-01

    The Red Sea exhibits a distinct seasonal overturning circulation. In winter, a typical two-layer exchange structure, with a fresher inflow from the Gulf of Aden on top of an outflow from the Red Sea, is established. In summer months (June to September) this circulation pattern is changed to a three-layer structure: a surface outflow from the Red Sea on top of a subsurface intrusion of the Gulf of Aden Intermediate Water and a weakened deep outflow. This seasonal variability is studied using a general circulation model, MITgcm, with 6 hourly NCEP atmospheric forcing. The model is able to reproduce the observed seasonal variability very well. The forcing mechanisms of the seasonal variability related to seasonal surface wind stress and buoyancy flux, and water mass transformation processes associated with the seasonal overturning circulation are analyzed and presented.

  10. Blocking device especially for circulating pumps

    International Nuclear Information System (INIS)

    Susil, J.; Vychodil, V.; Lorenc, P.

    1976-01-01

    The claim of the invention is a blocking device which blocks reverse flow occurring after the shutdown of circulating pumps, namely in the operation of nuclear power plants or in pumps with a high delivery head. (F.M.)

  11. Thermogenic effects of sibutramine and its metabolites

    Science.gov (United States)

    Connoley, Ian P; Liu, Yong-Ling; Frost, Ian; Reckless, Ian P; Heal, David J; Stock, Michael J

    1999-01-01

    The thermogenic activity of the serotonin and noradrenaline reuptake inhibitor sibutramine (BTS 54524; Reductil) was investigated by measuring oxygen consumption (VO2) in rats treated with sibutramine or its two pharmacologically-active metabolites. Sibutramine caused a dose-dependent rise in VO2, with a dose of 10 mg kg−1 of sibutramine or its metabolites producing increases of up to 30% that were sustained for at least 6 h, and accompanied by significant increases (0.5–1.0°C) in body temperature. Based on the accumulation in vivo of radiolabelled 2-deoxy-[3H]-glucose, sibutramine had little or no effect on glucose utilization in most tissues, but caused an 18 fold increase in brown adipose tissue (BAT). Combined high, non-selective doses (20 mg kg−1) of the β-adrenoceptor antagonists, atenolol and ICI 118551, inhibited completely the VO2 response to sibutramine, but the response was unaffected by low, β1-adrenoceptor-selective (atenolol) or β2-adrenoceptor-selective (ICI 118551) doses (1 mg kg−1). The ganglionic blocking agent, chlorisondamine (15 mg kg−1), inhibited completely the VO2 response to the metabolites of sibutramine, but had no effect on the thermogenic response to the β3-adrenoceptor-selective agonist BRL 35135. Similar thermogenic responses were produced by simultaneous injection of nisoxetine and fluoxetine at doses (30 mg kg−1) that had no effect on VO2 when injected individually. It is concluded that stimulation of thermogenesis by sibutramine requires central reuptake inhibition of both serotonin and noradrenaline, resulting in increased efferent sympathetic activation of BAT thermogenesis via β3-adrenoceptor, and that this contributes to the compound's activity as an anti-obesity agent. PMID:10217544

  12. Estuarine turbidity, flushing, salinity, and circulation

    Science.gov (United States)

    Pritchard, D. W.

    1972-01-01

    The effects of estuarine turbidity, flushing, salinity, and circulation on the ecology of the Chesapeake Bay are discussed. The sources of fresh water, the variations in salinity, and the circulation patterns created by temperature and salinity changes are analyzed. The application of remote sensors for long term observation of water temperatures is described. The sources of sediment and the biological effects resulting from increased sediments and siltation are identified.

  13. [Circulating tumor cells: cornerstone of personalized medicine].

    Science.gov (United States)

    Rafii, A; Vidal, F; Rathat, G; Alix-Panabières, C

    2014-11-01

    Cancer treatment has evolved toward personalized medicine. It is mandatory for clinicians to ascertain tumor biological features in order to optimize patients' treatment. Identification and characterization of circulating tumor cells demonstrated a prognostic value in many solid tumors. Here, we describe the main technologies for identification and characterization of circulating tumor cells and their clinical application in gynecologic and breast cancers. Copyright © 2014. Published by Elsevier Masson SAS.

  14. Themes on circulation in the third world.

    Science.gov (United States)

    Chapman, M; Prothero, R M

    1983-01-01

    "This article focuses upon circulation, or reciprocal flows of people, with specific reference to Third World societies." Aspects considered include attempts to standardize terminology and to formulate typologies of population movement; the development of explanatory models of circulation and modernization, social networks, family welfare, and capitalism; and "the transfer of methods and concepts to societies and populations different from those from which they initially evolved and in which they were first tested." excerpt

  15. Analysis of arsenical metabolites in biological samples.

    Science.gov (United States)

    Hernandez-Zavala, Araceli; Drobna, Zuzana; Styblo, Miroslav; Thomas, David J

    2009-11-01

    Quantitation of iAs and its methylated metabolites in biological samples provides dosimetric information needed to understand dose-response relations. Here, methods are described for separation of inorganic and mono-, di-, and trimethylated arsenicals by thin layer chromatography. This method has been extensively used to track the metabolism of the radionuclide [(73)As] in a variety of in vitro assay systems. In addition, a hydride generation-cryotrapping-gas chromatography-atomic absorption spectrometric method is described for the quantitation of arsenicals in biological samples. This method uses pH-selective hydride generation to differentiate among arsenicals containing trivalent or pentavalent arsenic.

  16. Hydroxylated polychlorinated biphenyls decrease circulating steroids in female polar bears (Ursus maritimus).

    Science.gov (United States)

    Gustavson, Lisa; Ciesielski, Tomasz M; Bytingsvik, Jenny; Styrishave, Bjarne; Hansen, Martin; Lie, Elisabeth; Aars, Jon; Jenssen, Bjørn M

    2015-04-01

    As a top predator in the Arctic food chain, polar bears (Ursus maritimus) are exposed to high levels of persistent organic pollutants (POPs). Because several of these compounds have been reported to alter endocrine pathways, such as the steroidogenesis, potential disruption of the sex steroid synthesis by POPs may cause implications for reproduction by interfering with ovulation, implantation and fertility. Blood samples were collected from 15 female polar bears in Svalbard (Norway) in April 2008. The concentrations of nine circulating steroid hormones; dehydroepiandrosterone (DHEA), androstenedione (AN), testosterone (TS), dihydrotestosterone (DHT), estrone (E1), 17α-estradiol (αE2), 17β-estradiol (βE2), pregnenolone (PRE) and progesterone (PRO) were determined. The aim of the study was to investigate associations among circulating levels of specific POP compounds and POP-metabolites (hydroxylated PCBs [OH-PCBs] and hydroxylated PBDEs [OH-PBDEs]), steroid hormones, biological and capture variables in female polar bears. Inverse correlations were found between circulating levels of PRE and AN, and circulating levels of OH-PCBs. There were no significant relationships between the steroid concentrations and other analyzed POPs or the variables capture date and capture location (latitude and longitude), lipid content, condition and body mass. Although statistical associations do not necessarily represent direct cause-effect relationships, the present study indicate that OH-PCBs may affect the circulating levels of AN and PRE in female polar bears and that OH-PCBs thus may interfere with the steroid homeostasis. Increase in PRO and a decrease in AN concentrations suggest that the enzyme CYP17 may be a potential target for OH-PCBs. In combination with natural stressors, ongoing climate change and contaminant exposure, it is possible that OH-PCBs may disturb the reproductive potential of polar bears. Copyright © 2015 Elsevier Inc. All rights reserved.

  17. Surgical myocardial revascularization without extracorporeal circulation

    Directory of Open Access Journals (Sweden)

    Salomón Soriano Ordinola Rojas

    2003-05-01

    Full Text Available OBJECTIVE: To assess the immediate postoperative period of patients undergoing myocardial revascularization without extracorporeal circulation with different types of grafts. METHODS: One hundred and twelve patients, 89 (79.5% of whom were males, were revascularized without extracorporeal circulation. Their ages ranged from 39 to 85 years. The criteria for indicating myocardial revascularization without extracorporeal circulation were as follows: revascularized coronary artery caliber > 1.5 mm, lack of intramyocardial trajectory on coronary angiography, noncalcified coronary arteries, and tolerance of the heart to the different rotation maneuvers. RESULTS: Myocardial revascularization without extracorporeal circulation was performed in 112 patients. Three were converted to extracorporeal circulation, which required a longer hospital stay but did not impact mortality. During the procedure, the following events were observed: atrial fibrillation in 10 patients, ventricular fibrillation in 4, total transient atrioventricular block in 2, ventricular extrasystoles in 58, use of a device to retrieve red blood cells in 53, blood transfusion in 8, and arterial hypotension in 89 patients. Coronary angiography was performed in 20 patients on the seventh postoperative day when the grafts were patent. CONCLUSION: Myocardial revascularization without extracorporeal circulation is a reproducible technique that is an alternative for treating ischemic heart disease.

  18. [Identification of saponins from Panax notoginseng in metabolites of rats].

    Science.gov (United States)

    Shen, Wen-Wen; Zhang, Yin; Qiu, Shou-Bei; Zhu, Fen-Xia; Jia, Xiao-Bin; Tang, Dao-Quan; Chen, Bin

    2017-10-01

    UPLC-QTOF-MS/MS was used to identify metabolites in rat blood, urine and feces after the administration of n-butanol extract derived from steamed notoginseng. The metabolic process of saponins came from steamed notoginseng was analyzed. The metabolites were processed by PeakView software, and identified according to the structural characteristics of prototype compounds and the accurate qualitative and quantitative changes of common metabolic pathways. Four saponins metabolites were identified based on MS/MS information of metabolites, namely ginsenoside Rh₄, Rk₃, Rk₁, Rg₅,and their 15 metabolites were verified. The metabolic pathways of the four ginsenosides in n-butanol extract included glucuronidation, desugar, sulfation, dehydromethylation, and branch loss. The metabolites of main active saponin components derived from steamed Panax notoginseng were analyzed from the perspective of qualitative analysis. And the material basis for the efficacy of steamed notoginseng was further clarified. Copyright© by the Chinese Pharmaceutical Association.

  19. Analysis of reverse flow in inverted U-tubes of steam generator under natural circulation condition

    International Nuclear Information System (INIS)

    Yang Ruichang; Liu Ruolei; Liu Jinggong; Qin Shiwei

    2008-01-01

    In this paper, we report on the analysis of reverse flow in inverted U-tubes of a steam generator under natural circulation condition. The mechanism of reverse flow in inverted U-tubes of the steam generator with natural circulation is graphically analyzed by using the full-range characteristic curve of parallel U-tubes. The mathematical model and numerical calculation method for analyzing the reverse flow in inverted U-tubes of the steam generator with natural circulation have been developed. The reverse flow in an inverted U-tube steam generator of a simulated pressurized water reactor with natural circulation in analyzed. Through the calculation, the mass flow rates of normal and reverse flows in individual U-tubes are obtained. The predicted sharp drop of the fluid temperature in the inlet plenum of the steam generator due to reverse flow agrees very well with the experimental data. This indicates that the developed mathematical model and solution method can be used to correctly predict the reverse flow in the inverted U-tubes of the steam generator with natural circulation. The obtained results also show that in the analysis of natural circulation flow in the primary circuit, the reverse flow in the inverted U-tubes of the steam generator must be taken into account. (author)

  20. Antarctic glaciation caused ocean circulation changes at the Eocene-Oligocene transition.

    Science.gov (United States)

    Goldner, A; Herold, N; Huber, M

    2014-07-31

    Two main hypotheses compete to explain global cooling and the abrupt growth of the Antarctic ice sheet across the Eocene-Oligocene transition about 34 million years ago: thermal isolation of Antarctica due to southern ocean gateway opening, and declining atmospheric CO2 (refs 5, 6). Increases in ocean thermal stratification and circulation in proxies across the Eocene-Oligocene transition have been interpreted as a unique signature of gateway opening, but at present both mechanisms remain possible. Here, using a coupled ocean-atmosphere model, we show that the rise of Antarctic glaciation, rather than altered palaeogeography, is best able to explain the observed oceanographic changes. We find that growth of the Antarctic ice sheet caused enhanced northward transport of Antarctic intermediate water and invigorated the formation of Antarctic bottom water, fundamentally reorganizing ocean circulation. Conversely, gateway openings had much less impact on ocean thermal stratification and circulation. Our results support available evidence that CO2 drawdown--not gateway opening--caused Antarctic ice sheet growth, and further show that these feedbacks in turn altered ocean circulation. The precise timing and rate of glaciation, and thus its impacts on ocean circulation, reflect the balance between potentially positive feedbacks (increases in sea ice extent and enhanced primary productivity) and negative feedbacks (stronger southward heat transport and localized high-latitude warming). The Antarctic ice sheet had a complex, dynamic role in ocean circulation and heat fluxes during its initiation, and these processes are likely to operate in the future.

  1. Primary productivity

    Digital Repository Service at National Institute of Oceanography (India)

    Verlecar, X.N.; Parulekar, A.H.

    Photosynthetic production in the oceans in relation to light, nutrients and mixing processes is discussed. Primary productivity in the estuarine region is reported to be high in comparison to coastal and oceanic waters. Upwelling phenomenon...

  2. Primary Hyperparathyroidism

    Science.gov (United States)

    ... Neoplasia Type 1 Thyroid Disease & Pregnancy Primary Hyperparathyroidism Prolactinoma National Hormone and Pituitary Program (NHPP): Information for ... qualified health care provider nearby. Eating, Diet, and Nutrition Eating, diet, and nutrition have not been shown ...

  3. Primary Myelofibrosis

    Science.gov (United States)

    ... attack is higher. Patients also have an increased risk of acute myeloid leukemia or primary myelofibrosis . Symptoms of polycythemia vera include headaches and a feeling of fullness below the ribs on the left ...

  4. Metabolite changes in nine different soybean varieties grown under field and greenhouse conditions.

    Science.gov (United States)

    Maria John, K M; Natarajan, Savithiry; Luthria, Devanand L

    2016-11-15

    Global food security remains a worldwide concern due to changing climate, increasing population, and reduced agriculture acreages. Greenhouse cultivation increases productivity by extending growing seasons, reducing pest infestations and providing protection against short term drastic weather fluctuations like frost, heat, rain, and wind. In the present study, we examined and compared the metabolic responses of nine soybean varieties grown under field and greenhouse conditions. Extracts were assayed by GC-FID, GC-MS, and LC-MS for the identification of 10 primary (amino acids, organic acids, and sugars) and 10 secondary (isoflavones, fatty acid methyl esters) metabolites. Sugar molecules (glucose, sucrose, and pinitol) and isoflavone aglycons were increased but the isoflavones glucoside content decreased in the greenhouse cultivated soybeans. The amino acids and organic acids varied between the varieties. The results show that clustering (PCA and PLS-DA) patterns of soybean metabolites were significantly influenced by the genetic variation and growing conditions. Published by Elsevier Ltd.

  5. Fruit metabolite networks in engineered and non-engineered tomato genotypes reveal fluidity in a hormone and agroecosystem specific manner.

    Science.gov (United States)

    Fatima, Tahira; Sobolev, Anatoly P; Teasdale, John R; Kramer, Matthew; Bunce, Jim; Handa, Avtar K; Mattoo, Autar K

    Metabolomics provides a view of endogenous metabolic patterns not only during plant growth, development and senescence but also in response to genetic events, environment and disease. The effects of the field environment on plant hormone-specific metabolite profiles are largely unknown. Few studies have analyzed useful phenotypes generated by introducing single or multiple gene events alongside the non-engineered wild type control at field scale to determine the robustness of the genetic trait and its modulation in the metabolome as a function of specific agroecosystem environments. We evaluated the influence of genetic background (high polyamine lines; low methyl jasmonate line; low ethylene line; and isogenic genotypes carrying double transgenic events) and environments (hairy vetch, rye, plastic black mulch and bare soil mulching systems) on the metabolomic profile of isogenic reverse genetic mutations and selected mulch based cropping systems in tomato fruit. Net photosynthesis and fruit yield were also determined. NMR spectroscopy was used for quantifying metabolites that are central to primary metabolism. We analyzed both the first moment (means) of metabolic response to genotypes and agroecosystems by traditional univariate/multivariate methods, and the second moment (covariances) of responses by creating networks that depicted changes in correlations of paired metabolites. This particular approach is novel and was necessary because our experimental material yielded highly variable metabolic responses that could not be easily understood using the traditional analytical approaches for first moment statistics. High endogenous spermidine and spermine content exhibited strong effects on amino acids, Krebs cycle intermediates and energy molecules (ADP + ATP) in ripening fruits of plants grown under different agroecosystem environments. The metabolic response to high polyamine genotypes was similar to the response to hairy vetch cover crop mulch; supported by

  6. Metabolomic Analysis and Mode of Action of Metabolites of Tea Tree Oil Involved in the Suppression of Botrytis cinerea

    Directory of Open Access Journals (Sweden)

    Jiayu Xu

    2017-06-01

    Full Text Available Tea tree oil (TTO, a volatile essential oil, has been widely used as an antimicrobial agent. However, the mechanism underlying TTO antifungal activity is not fully understood. In this study, a comprehensive metabolomics survey was undertaken to identify changes in metabolite production in Botrytis cinerea cells treated with TTO. Significant differences in 91 metabolites were observed, including 8 upregulated and 83 downregulated metabolites in TTO-treated cells. The results indicate that TTO inhibits primary metabolic pathways through the suppression of the tricarboxylic acid (TCA cycle and fatty acid metabolism. Further experiments show that TTO treatment decreases the activities of key enzymes in the TCA cycle and increases the level of hydrogen peroxide (H2O2. Membrane damage is also induced by TTO treatment. We hypothesize that the effect of TTO on B. cinerea is achieved mainly by disruption of the TCA cycle and fatty acid metabolism, resulting in mitochondrial dysfunction and oxidative stress.

  7. Experimental investigation on a 0.35 MWth coal-fired horizontal circulating fluidized bed boiler

    Energy Technology Data Exchange (ETDEWEB)

    Meng, Aihong; Li, Qinghai; Zhang, Yanguo; Wang, Zhaojun; Dang, Wenda [Tsinghua Univ., Beijing (China); Ministry of Education, Beijing (China). Key Lab. for Thermal Science and Power Engineering

    2013-07-01

    The capacities of industrial coal-fired boilers are normally less than 20-30 MWe. And these coal-fired boilers of low capacity are facing the severe situation of low efficiency and heavy environmental pollution. Hence, an innovative horizontal circulating fluidized bed (HCFB) boiler was developed to enhance heat efficiency and reduce pollutant emission of industrial boilers in China. The chamber in the HCFB boiler consists of primary combustion chamber, secondary combustion chamber and burnout chamber, which were combined horizontally side by side. To verify the conception of horizontal fluidized circulation and to obtain the characteristic data, a 0.35 MWth coal-combustion HCFB boiler was designed and installed to perform some experiments of combustion and mass circulation. In the boiler there were two mass circulating paths, one is inner circulating through the inertia separator and another was external circulating through the cyclone separator. The connection bottom of the secondary chamber and the burnout chamber was designed as an inertia separator, in which separated and collected solid materials were returned to the primary combustion. In fact the secondary separator was a small cyclone separator connecting to the exit of the burnout chamber. Heat efficiency and separating efficiency of the experimental boiler were measured and analyzed. Furthermore, mass and temperature distribution along the chambers height were also investigated. The results showed that the heat efficiency of the bare boiler was 82%. The mass balance based on ash content was measured and analyzed. Separating efficiency of the inertia separator and cyclone separator was 60 and 99.9%, respectively. It showed that the two stage material separation and circulation enhanced coal combustion in the HCFB boiler and help to minimize the height of the furnace.

  8. A latex metabolite benefits plant fitness under root herbivore attack

    OpenAIRE

    Huber, M.; Epping, J.; Gronover, C.S.; Fricke, J.; Aziz, Z.; Brillatz, T.; Swyers, M.; Köllner, T.G.; Vogel, H.; Hammerbacher, A.; Triebwasser-Freese, D.; Robert, C.A.M.; Verhoeven, K.; Preite, V.; Gershenzon, J.

    2016-01-01

    Plants produce large amounts of secondary metabolites in their shoots and roots and store them in specialized secretory structures. Although secondary metabolites and their secretory structures are commonly assumed to have a defensive function, evidence that they benefit plant fitness under herbivore attack is scarce, especially below ground. Here, we tested whether latex secondary metabolites produced by the common dandelion (Taraxacum officinale agg.) decrease the performance of its major n...

  9. Novel pyrazine metabolites found in polymyxin biosynthesis by Paenibacillus polymyxa

    DEFF Research Database (Denmark)

    Beck, Hans Christian; Hansen, Anne M; Lauritsen, Frants R

    2003-01-01

    A complex mixture of methyl-branched alkyl-substituted pyrazines was found in the growth medium of the polymyxin-producing bacterium Paenibacillus polymyxa, and of these, seven are new natural compounds. A total of 19 pyrazine metabolites were identified. The dominant metabolite was 2...... supplementation. The other pyrazine metabolites, all related pyrazines with either one, two or three alkyl substituents, were identified by means of their mass spectral data and/or co-elution with authentic standards....

  10. Cyanobacteria as Cell Factories to Produce Plant Secondary Metabolites

    OpenAIRE

    Xue, Yong; He, Qingfang

    2015-01-01

    Cyanobacteria represent a promising platform for the production of plant secondary metabolites. Their capacity to express plant P450 proteins, which have essential functions in the biosynthesis of many plant secondary metabolites, makes cyanobacteria ideal for this purpose, and their photosynthetic capability allows cyanobacteria to grow with simple nutrient inputs. This review summarizes the advantages of using cyanobacteria to transgenically produce plant secondary metabolites. Some techniq...

  11. Metabolite Profiles of Lactic Acid Bacteria in Grass Silage▿

    OpenAIRE

    Broberg, Anders; Jacobsson, Karin; Ström, Katrin; Schnürer, Johan

    2007-01-01

    The metabolite production of lactic acid bacteria (LAB) on silage was investigated. The aim was to compare the production of antifungal metabolites in silage with the production in liquid cultures previously studied in our laboratory. The following metabolites were found to be present at elevated concentrations in silos inoculated with LAB strains: 3-hydroxydecanoic acid, 2-hydroxy-4-methylpentanoic acid, benzoic acid, catechol, hydrocinnamic acid, salicylic acid, 3-phenyllactic acid, 4-hydro...

  12. Exometabolomic Analysis of Cross-Feeding Metabolites.

    Science.gov (United States)

    Lubbe, Andrea; Bowen, Benjamin P; Northen, Trent

    2017-10-04

    Microbial consortia have the potential to perform complex, industrially important tasks. The design of microbial consortia requires knowledge of the substrate preferences and metabolic outputs of each member, to allow understanding of potential interactions such as competition and beneficial metabolic exchange. Here, we used exometabolite profiling to follow the resource processing by a microbial co-culture of two biotechnologically relevant microbes, the bacterial cellulose degrader Cellulomonas fimi, and the oleaginous yeast Yarrowia lipolytica. We characterized the substrate preferences of the two strains on compounds typically found in lignocellulose hydrolysates. This allowed prediction that specific sugars resulting from hemicellulose polysaccharide degradation by C. fimi may serve as a cross-feeding metabolites to Y. lipolytica in co-culture. We also showed that products of ionic liquid-treated switchgrass lignocellulose degradation by C. fimi were channeled to Y. lipolytica in a co-culture. Additionally, we observed metabolites, such as shikimic acid accumulating in the co-culture supernatants, suggesting the potential for producing interesting co-products. Insights gained from characterizing the exometabolite profiles of individual and co-cultures of the two strains can help to refine this interaction, and guide strategies for making this an industrially viable co-culture to produce valuable products from lignocellulose material.

  13. Involvement of a volatile metabolite during phosphoramide mustard-induced ovotoxicity

    Energy Technology Data Exchange (ETDEWEB)

    Madden, Jill A. [Department of Animal Science, Iowa State University, Ames, IA 50011 (United States); Hoyer, Patricia B. [Department of Physiology, University of Arizona, Tucson, AZ 85724 (United States); Devine, Patrick J. [INRS—Institut Armand-Frappier Research Centre, University of Quebec, Laval, QC H7V 1B7 (Canada); Keating, Aileen F., E-mail: akeating@iastate.edu [Department of Animal Science, Iowa State University, Ames, IA 50011 (United States); Department of Physiology, University of Arizona, Tucson, AZ 85724 (United States)

    2014-05-15

    The finite ovarian follicle reserve can be negatively impacted by exposure to chemicals including the anti-neoplastic agent, cyclophosphamide (CPA). CPA requires bioactivation to phosphoramide mustard (PM) to elicit its therapeutic effects however; in addition to being the tumor-targeting metabolite, PM is also ovotoxic. In addition, PM can break down to a cytotoxic, volatile metabolite, chloroethylaziridine (CEZ). The aim of this study was initially to characterize PM-induced ovotoxicity in growing follicles. Using PND4 Fisher 344 rats, ovaries were cultured for 4 days before being exposed once to PM (10 or 30 μM). Following eight additional days in culture, relative to control (1% DMSO), PM had no impact on primordial, small primary or large primary follicle number, but both PM concentrations induced secondary follicle depletion (P < 0.05). Interestingly, a reduction in follicle number in the control-treated ovaries was observed. Thus, the involvement of a volatile, cytotoxic PM metabolite (VC) in PM-induced ovotoxicity was explored in cultured rat ovaries, with control ovaries physically separated from PM-treated ovaries during culture. Direct PM (60 μM) exposure destroyed all stage follicles after 4 days (P < 0.05). VC from nearby wells depleted primordial follicles after 4 days (P < 0.05), temporarily reduced secondary follicle number after 2 days, and did not impact other stage follicles at any other time point. VC was determined to spontaneously liberate from PM, which could contribute to degradation of PM during storage. Taken together, this study demonstrates that PM and VC are ovotoxicants, with different follicular targets, and that the VC may be a major player during PM-induced ovotoxicity observed in cancer survivors. - Highlights: • PM depletes all stage ovarian follicles in a temporal pattern. • A volatile ovotoxic compound is liberated from PM. • The volatile metabolite depletes primordial follicles.

  14. Primary metabolite mobilization during germination in rosewood (Aniba rosaeodora Ducke seeds Mobilização de metabólitos primários durante a germinação de sementes de pau-rosa (Aniba rosaeodora Ducke

    Directory of Open Access Journals (Sweden)

    Renata Braga Souza Lima

    2008-02-01

    Full Text Available This study aimed to characterize protein, oil, starch and soluble sugar mobilization as well as the activity of alpha-amylase during rosewood seed germination. Germination test was carried out at 25°C and the following parameters were analyzed: percentage of germination, initial, average, and final germination time. Seed reserve quantification was monitored in quiescent seeds and during different stages of radicle growth. Starch mobilization was studied in function of a-amylase activity. Germination reached 87.5% at the initial, average, and final time of 16, 21 and 30 days, respectively. Oil mobilization showed a negative linear behavior, decreasing 40% between the first and the last stage analyzed, whereas protein levels increased 34.7% during the initial period of germination. Starch content (46.4% was the highest among those of the metabolites analyzed and starch mobilization occurred inversely to the observed for soluble sugars; alpha-amylase activity increased until the 15th day, a period before radicle emission and corresponding to the highest starch mobilization. The high percentage of rosewood seed germination may be related to the controlled condition used in the germination chamber as well as to high seed reserve mobilization, in special oil and starch.Este estudo teve por objetivo caracterizar a mobilização de metabólitos primários (proteínas, óleos, amido e açúcares solúveis e determinar a atividade da enzima alfa-amilase em sementes de pau-rosa durante diferentes períodos da germinação. Sementes quiescentes, após a assepsia, foram postas para germinar a 25 °C, analisando-se as seguintes variáveis: porcentagem de germinação e tempos inicial, médio e final de germinação. A quantificação das reservas orgânicas foi monitorada nas sementes quiescentes e nos diferentes estágios de crescimento da radícula. A mobilização do amido foi monitorada mediante a atividade da enzima alfa-amilase. A germinação atingiu

  15. Reparation and Immunomodulating Properties of Bacillus sp. Metabolites from Permafrost.

    Science.gov (United States)

    Kalenova, L F; Melnikov, V P; Besedin, I M; Bazhin, A S; Gabdulin, M A; Kolyvanova, S S

    2017-09-01

    An ointment containing metabolites of Bacillus sp. microorganisms isolated from permafrost samples was applied onto the skin wound of BALB/c mice. Metabolites isolated during culturing of Bacillus sp. at 37°C produced a potent therapeutic effect and promoted wound epithelialization by 30% in comparison with the control (ointment base) and by 20% in comparison with Solcoseryl. Treatment with Bacillus sp. metabolites stimulated predominantly humoral immunity, reduced the time of wound contraction and the volume of scar tissue, and promoted complete hair recovery. These metabolites can be considered as modulators of the wound process with predominance of regeneration mechanisms.

  16. Prospective study of blood metabolites associated with colorectal cancer risk.

    Science.gov (United States)

    Shu, Xiang; Xiang, Yong-Bing; Rothman, Nathaniel; Yu, Danxia; Li, Hong-Lan; Yang, Gong; Cai, Hui; Ma, Xiao; Lan, Qing; Gao, Yu-Tang; Jia, Wei; Shu, Xiao-Ou; Zheng, Wei

    2018-02-26

    Few prospective studies, and none in Asians, have systematically evaluated the relationship between blood metabolites and colorectal cancer risk. We conducted a nested case-control study to search for risk-associated metabolite biomarkers for colorectal cancer in an Asian population using blood samples collected prior to cancer diagnosis. Conditional logistic regression was performed to assess associations of metabolites with cancer risk. In this study, we included 250 incident cases with colorectal cancer and individually matched controls nested within two prospective Shanghai cohorts. We found 35 metabolites associated with risk of colorectal cancer after adjusting for multiple comparisons. Among them, 12 metabolites were glycerophospholipids including nine associated with reduced risk of colorectal cancer and three with increased risk [odds ratios per standard deviation increase of transformed metabolites: 0.31-1.98; p values: 0.002-1.25 × 10 -10 ]. The other 23 metabolites associated with colorectal cancer risk included nine lipids other than glycerophospholipid, seven aromatic compounds, five organic acids and four other organic compounds. After mutual adjustment, nine metabolites remained statistically significant for colorectal cancer. Together, these independently associated metabolites can separate cancer cases from controls with an area under the curve of 0.76 for colorectal cancer. We have identified that dysregulation of glycerophospholipids may contribute to risk of colorectal cancer. © 2018 UICC.

  17. Novel pyrazine metabolites found in polymyxin biosynthesis by Paenibacillus polymyxa

    DEFF Research Database (Denmark)

    Beck, Hans Christian; Hansen, Anne M; Lauritsen, Frants R

    2003-01-01

    A complex mixture of methyl-branched alkyl-substituted pyrazines was found in the growth medium of the polymyxin-producing bacterium Paenibacillus polymyxa, and of these, seven are new natural compounds. A total of 19 pyrazine metabolites were identified. The dominant metabolite was 2,5-diisoprop......A complex mixture of methyl-branched alkyl-substituted pyrazines was found in the growth medium of the polymyxin-producing bacterium Paenibacillus polymyxa, and of these, seven are new natural compounds. A total of 19 pyrazine metabolites were identified. The dominant metabolite was 2...

  18. Differentiation-Dependent Energy Production and Metabolite Utilization: A Comparative Study on Neural Stem Cells, Neurons, and Astrocytes

    Science.gov (United States)

    Jády, Attila Gy.; Nagy, Ádám M.; Kőhidi, Tímea; Ferenczi, Szilamér; Tretter, László

    2016-01-01

    While it is evident that the metabolic machinery of stem cells should be fairly different from that of differentiated neurons, the basic energy production pathways in neural stem cells (NSCs) or in neurons are far from clear. Using the model of in vitro neuron production by NE-4C NSCs, this study focused on the metabolic changes taking place during the in vitro neuronal differentiation. O2 consumption, H+ production, and metabolic responses to single metabolites were measured in cultures of NSCs and in their neuronal derivatives, as well as in primary neuronal and astroglial cultures. In metabolite-free solutions, NSCs consumed little O2 and displayed a higher level of mitochondrial proton leak than neurons. In stem cells, glycolysis was the main source of energy for the survival of a 2.5-h period of metabolite deprivation. In contrast, stem cell-derived or primary neurons sustained a high-level oxidative phosphorylation during metabolite deprivation, indicating the consumption of own cellular material for energy production. The stem cells increased O2 consumption and mitochondrial ATP production in response to single metabolites (with the exception of glucose), showing rapid adaptation of the metabolic machinery to the available resources. In contrast, single metabolites did not increase the O2 consumption of neurons or astrocytes. In “starving” neurons, neither lactate nor pyruvate was utilized for mitochondrial ATP production. Gene expression studies also suggested that aerobic glycolysis and rapid metabolic adaptation characterize the NE-4C NSCs, while autophagy and alternative glucose utilization play important roles in the metabolism of stem cell-derived neurons. PMID:27116891

  19. Comparative metabolome analysis of wheat embryo and endosperm reveals the dynamic changes of metabolites during seed germination.

    Science.gov (United States)

    Han, Caixia; Zhen, Shoumin; Zhu, Gengrui; Bian, Yanwei; Yan, Yueming

    2017-06-01

    In this study, we performed the first comparative metabolomic analysis of the wheat embryo and endosperm during seed germination using GC-MS/MS. In total, 82 metabolites were identified in the embryo and endosperm. Principal component analysis (PCA), metabolite-metabolite correlation and hierarchical cluster analysis (HCA) revealed distinct dynamic changes in metabolites between the embryo and endosperm during seed germination. Generally, the metabolite changes in the embryo were much greater than those in the endosperm, suggesting that the embryo is more active than the endosperm during seed germination. Most amino acids were upregulated in both embryo and endosperm, while polysaccharides and organic acids associated with sugars were mainly downregulated in the embryo. Most of the sugars showed an upregulated trend in the endosperm, but significant changes in lipids occurred only in the embryo. Our results suggest that the embryo mobilises mainly protein and lipid metabolism, while the endosperm mobilises storage starch and minor protein metabolism during seed germination. The primary energy was generated mainly in the embryo by glycolysis during seed imbibition. The embryo containing most of the genetic information showed increased nucleotides during seed germination process, indicating more active transcription and translation metabolisms. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  20. Secondary metabolite profiling of Curcuma species grown at different locations using GC/TOF and UPLC/Q-TOF MS.

    Science.gov (United States)

    Lee, Jueun; Jung, Youngae; Shin, Jeoung-Hwa; Kim, Ho Kyoung; Moon, Byeong Cheol; Ryu, Do Hyun; Hwang, Geum-Sook

    2014-07-04

    Curcuma, a genus of rhizomatous herbaceous species, has been used as a spice, traditional medicine, and natural dye. In this study, the metabolite profile of Curcuma extracts was determined using gas chromatography-time of flight mass spectrometry (GC/TOF MS) and ultrahigh-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC/Q-TOF MS) to characterize differences between Curcuma aromatica and Curcuma longa grown on the Jeju-do or Jin-do islands, South Korea. Previous studies have performed primary metabolite profiling of Curcuma species grown in different regions using NMR-based metabolomics. This study focused on profiling of secondary metabolites from the hexane extract of Curcuma species. Principal component analysis (PCA) and partial least-squares discriminant analysis (PLS-DA) plots showed significant differences between the C. aromatica and C. longa metabolite profiles, whereas geographical location had little effect. A t-test was performed to identify statistically significant metabolites, such as terpenoids. Additionally, targeted profiling using UPLC/Q-TOF MS showed that the concentration of curcuminoids differed depending on the plant origin. Based on these results, a combination of GC- and LC-MS allowed us to analyze curcuminoids and terpenoids, the typical bioactive compounds of Curcuma, which can be used to discriminate Curcuma samples according to species or geographical origin.

  1. Role of the phosphopantetheinyltransferase enzyme, PswP, in the biosynthesis of antimicrobial secondary metabolites by Serratia marcescens Db10.

    Science.gov (United States)

    Gerc, Amy J; Stanley-Wall, Nicola R; Coulthurst, Sarah J

    2014-08-01

    Phosphopantetheinyltransferase (PPTase) enzymes fulfil essential roles in primary and secondary metabolism in prokaryotes, archaea and eukaryotes. PPTase enzymes catalyse the essential modification of the carrier protein domain of fatty acid synthases, polyketide synthases (PKSs) and non-ribosomal peptide synthetases (NRPSs). In bacteria and fungi, NRPS and PKS enzymes are often responsible for the biosynthesis of secondary metabolites with clinically relevant properties; these secondary metabolites include a variety of antimicrobial peptides. We have previously shown that in the Gram-negative bacterium Serratia marcescens Db10, the PPTase enzyme PswP is essential for the biosynthesis of an NRPS-PKS dependent antibiotic called althiomycin. In this work we utilize bioinformatic analyses to classify PswP as belonging to the F/KES subfamily of Sfp type PPTases and to putatively identify additional NRPS substrates of PswP, in addition to the althiomycin NRPS-PKS, in Ser. marcescens Db10. We show that PswP is required for the production of three diffusible metabolites by this organism, each possessing antimicrobial activity against Staphylococcus aureus. Genetic analyses identify the three metabolites as althiomycin, serrawettin W2 and an as-yet-uncharacterized siderophore, which may be related to enterobactin. Our results highlight the use of an individual PPTase enzyme in multiple biosynthetic pathways, each contributing to the ability of Ser. marcescens to inhibit competitor bacteria by the production of antimicrobial secondary metabolites. © 2014 The Authors.

  2. Secondary Metabolite Profiling of Curcuma Species Grown at Different Locations Using GC/TOF and UPLC/Q-TOF MS

    Directory of Open Access Journals (Sweden)

    Jueun Lee

    2014-07-01

    Full Text Available Curcuma, a genus of rhizomatous herbaceous species, has been used as a spice, traditional medicine, and natural dye. In this study, the metabolite profile of Curcuma extracts was determined using gas chromatography-time of flight mass spectrometry (GC/TOF MS and ultrahigh-performance liquid chromatography–quadrupole time-of-flight mass spectrometry (UPLC/Q-TOF MS to characterize differences between Curcuma aromatica and Curcuma longa grown on the Jeju-do or Jin-do islands, South Korea. Previous studies have performed primary metabolite profiling of Curcuma species grown in different regions using NMR-based metabolomics. This study focused on profiling of secondary metabolites from the hexane extract of Curcuma species. Principal component analysis (PCA and partial least-squares discriminant analysis (PLS-DA plots showed significant differences between the C. aromatica and C. longa metabolite profiles, whereas geographical location had little effect. A t-test was performed to identify statistically significant metabolites, such as terpenoids. Additionally, targeted profiling using UPLC/Q-TOF MS showed that the concentration of curcuminoids differed depending on the plant origin. Based on these results, a combination of GC- and LC-MS allowed us to analyze curcuminoids and terpenoids, the typical bioactive compounds of Curcuma, which can be used to discriminate Curcuma samples according to species or geographical origin.

  3. Hypoxia, leukocytes, and the pulmonary circulation.

    Science.gov (United States)

    Stenmark, Kurt R; Davie, Neil J; Reeves, John T; Frid, Maria G

    2005-02-01

    Data are rapidly accumulating in support of the idea that circulating monocytes and/or mononuclear fibrocytes are recruited to the pulmonary circulation of chronically hypoxic animals and that these cells play an important role in the pulmonary hypertensive process. Hypoxic induction of monocyte chemoattractant protein-1, stromal cell-derived factor-1, vascular endothelial growth factor-A, endothelin-1, and tumor growth factor-beta(1) in pulmonary vessel wall cells, either directly or indirectly via signals from hypoxic lung epithelial cells, may be a critical first step in the recruitment of circulating leukocytes to the pulmonary circulation. In addition, hypoxic stress appears to induce release of increased numbers of monocytic progenitor cells from the bone marrow, and these cells may have upregulated expression of receptors for the chemokines produced by the lung circulation, which thus facilitates their specific recruitment to the pulmonary site. Once present, macrophages/fibrocytes may exert paracrine effects on resident pulmonary vessel wall cells stimulating proliferation, phenotypic modulation, and migration of resident fibroblasts and smooth muscle cells. They may also contribute directly to the remodeling process through increased production of collagen and/or differentiation into myofibroblasts. In addition, they could play a critical role in initiating and/or supporting neovascularization of the pulmonary artery vasa vasorum. The expanded vasa network may then act as a conduit for further delivery of circulating mononuclear cells to the pulmonary arterial wall, creating a feedforward loop of pathological remodeling. Future studies will need to determine the mechanisms that selectively induce leukocyte/fibrocyte recruitment to the lung circulation under hypoxic conditions, their direct role in the remodeling process via production of extracellular matrix and/or differentiation into myofibroblasts, their impact on the phenotype of resident smooth muscle

  4. Importance of circulating IGF-1 for normal cardiac morphology, function and post infarction remodeling.

    Science.gov (United States)

    Scharin Täng, M; Redfors, B; Lindbom, M; Svensson, J; Ramunddal, T; Ohlsson, C; Shao, Y; Omerovic, E

    2012-12-01

    IGF-1 plays an important role in cardiovascular homeostasis, and plasma levels of IGF-1 correlate inversely with systolic function in heart failure. It is not known to what extent circulating IGF-1 secreted by the liver and local autocrine/paracrine IGF-1 expressed in the myocardium contribute to these beneficial effects on cardiac function and morphology. In the present study, we used a mouse model of liver-specific inducible deletion of the IGF-1 gene (LI-IGF-1 -/- mouse) in an attempt to evaluate the importance of circulating IGF-I on cardiac morphology and function under normal and pathological conditions, with an emphasis on its regulatory role in myocardial phosphocreatine metabolism. Echocardiography was performed in LI-IGF-1 -/- and control mice at rest and during dobutamine stress, both at baseline and post myocardial infarction (MI). High-energy phosphate metabolites were compared between LI-IGF-1 -/- and control mice at 4 weeks post MI. We found that LI-IGF-1 -/- mice had significantly greater left ventricular dimensions at baseline and showed a greater relative increase in cardiac dimensions, as well as deterioration of cardiac function, post MI. Myocardial creatine content was 17.9% lower in LI-IGF-1 -/- mice, whereas there was no detectable difference in high-energy nucleotides. These findings indicate an important role of circulating IGF-1 in preserving cardiac structure and function both in physiological settings and post MI. Copyright © 2012 Elsevier Ltd. All rights reserved.

  5. Experiments on natural circulation during PWR severe accidents and their analysis

    International Nuclear Information System (INIS)

    Sehgal, B.R.; Stewart, W.A.; Sha, W.T.

    1988-01-01

    Buoyancy-induced natural circulation flows will occur during the early-part of PWR high pressure accident scenarios. These flows affect several key parameters; in particular, the course of such accidents will most probably change due to local failures occurring in the primary coolant system (CS) before substantial core degradation. Natural circulation flow patterns were measured in a one-seventh scale PWR PCS facility at Westinghouse RandD laboratories. The measured flow and temperature distributions are report in this paper. The experiments were analyzed with the COMMIX code and good agreement was obtained between data and calculations. 10 refs., 8 figs., 2 tabs

  6. Analysis of SBO accident and natural circulation of 49-2 swimming pool reactor

    International Nuclear Information System (INIS)

    Wu Yuanyuan; Liu Tiancai; Sun Wei

    2012-01-01

    The transient thermal hydraulic characteristics of 49-2 Swimming Pool Reactor (SPR) were analyzed by RELAP5/MOD3.3 code to verify the capability of natural circulation and minus reactivity feedback for accident mitigation under the condition of station blackout (SBO). Then, the effects on accident consequence and sequence for core channels and primary pumps were briefly discussed. The calculation results show that the reactor can be shutdown by the effect of minus reactivity feedback, and the residual heat can be removed through the stable natural circulation. Therefore, it demonstrates that the 49-2 SPR is safe during the accident of SBO. (authors)

  7. Hepatic Disposition of Gemfibrozil and Its Major Metabolite Gemfibrozil 1-O-β-Glucuronide.

    Science.gov (United States)

    Kimoto, Emi; Li, Rui; Scialis, Renato J; Lai, Yurong; Varma, Manthena V S

    2015-11-02

    Gemfibrozil (GEM), which decreases serum triglycerides and low density lipoprotein, perpetrates drug-drug interactions (DDIs) with several drugs. These DDIs are primarily attributed to the inhibition of drug transporters and metabolic enzymes, particularly cytochrome P450 (CYP) 2C8 by the major circulating metabolite gemfibrozil 1-O-β-glucuronide (GG). Here, we characterized the transporter-mediated hepatic disposition of GEM and GG using sandwich-cultured human hepatocytes (SCHH) and transporter-transfect systems. Significant active uptake was noted in SCHH for the metabolite. GG, but not GEM, showed substrate affinity to organic anion transporting polypeptide (OATP) 1B1, 1B3, and 2B1. In SCHH, glucuronidation was characterized affinity constants (Km) of 7.9 and 61.4 μM, and biliary excretion of GG was observed. Furthermore, GG showed active basolateral efflux from preloaded SCHH and ATP-dependent uptake into membrane vesicles overexpressing multidrug resistance-associated protein (MRP) 2, MRP3, and MRP4. A mathematical model was developed to estimate hepatic uptake and efflux kinetics of GEM and GG based on SCHH studies. Collectively, the hepatic transporters play a key role in the disposition and thus determine the local concentrations of GEM and more so for GG, which is the predominant inhibitory species against CYP2C8 and OATP1B1.

  8. 24,25,28-Trihydroxyvitamin D2 and 24,25,26-trihydroxyvitamin D2: Novel metabolites of vitamin D2

    International Nuclear Information System (INIS)

    Reddy, G.S.; Tserng, K.

    1990-01-01

    Understanding of the inactivation pathways of 25-hydroxyvitamin D 2 and 24-hydroxyvitamin D 2 , the two physiologically significant monohydroxylated metabolites of vitamin D 2 , is of importance, especially during hypervitaminosis D 2 . At present, little information is available regarding the inactivation pathway of 25-hydroxyvitamin D 2 except its further metabolism into 24,25-dihydroxyvitamin D 2 . In our present study, the authors investigated the metabolic fate of 25-hydroxyvitamin D 2 in the isolated perfused rat kidney and demonstrated its conversion not only into 24,25-dihydroxyvitamin D 2 but also into two other new metabolites, namely, 24,25,28-trihydroxyvitamin D 2 and 24,25,26-trihydroxyvitamin D 2 . The structure identification of the new metabolites was established by the techniques of ultraviolet absorption spectrophotometry and mass spectrometry and by the characteristic nature of each new metabolite's susceptibility to sodium metaperiodate oxidation. In order to demonstrate the physiological significance of the two new trihydroxy metabolites of vitamin D 2 , induced hypervitaminosis D 2 in a rat using [3α- 3 H]vitamin D 2 and analyzed its plasma for the various [3α- 3 H]vitamin D 2 metabolites on two different high-pressure liquid chromatography systems. The results indicate that both 24,25,26-trihydroxyvitamin D 2 and 24,25,26-trihydroxyvitamin D 2 circulate in the vitamin D 2 intoxicated rat in significant amounts along with other previously identified monohydroxy and dihydroxy metabolites of vitamin D 2 , namely, 24-hydroxyvitamin D 2 , 25-hydroxyvitamin D 2 , and 24,25-dihydroxyvitamin D 2

  9. Estrogen Metabolites Are Not Associated With Colorectal Cancer Risk In Postmenopausal Women

    Science.gov (United States)

    Falk, Roni T.; Dallal, Cher M.; Lacey, James V.; Bauer, Douglas C.; Buist, Diana SM; Cauley, Jane A.; Hue, Trisha F.; LaCroix, Andrea; Tice, Jeffrey A.; Pfeiffer, Ruth M.; Xu, Xia; Veenstra, Timothy D.; Brinton, Louise A.

    2015-01-01

    Background A potential protective role for estrogen in colon carcinogenesis has been suggested based on exogenous hormone use, but it is unclear from previous studies whether endogenous estrogens are related to colorectal cancer (CRC) risk. These few prior studies focused on parent estrogens; none evaluated effects of estrogen metabolism in postmenopausal women. Methods We followed 15,595 women (ages 55–80) enrolled in B~FIT (Breast and Bone Follow-up to the Fracture Intervention Trial (FIT)) who donated blood between 1992 and 1993 for cancer through December 2004. A panel of 15 estrogen metabolites (EM), including estradiol and estrone, were measured in serum from 187 CRC cases and a subcohort of 501 women not using exogenous hormones at blood draw. We examined EM individually, grouped by pathway (hydroxylation at the C-2, C-4, or C-16 position), and by ratios of the groupings using Cox proportional hazards regression models. Results No significant associations were seen for estrone (HRQ4 v Q1=1.15, 95% CI=0.69–1.93, ptrend=0.54), estradiol (HRQ4 v Q1= 0.98, 95% CI=0.58–1.64, ptrend>0.99) or total EM (the sum of all EM; HRQ4 v Q1=1.35. 95% CI=0.81–2.24, ptrend=0.33). Most metabolites in the 2-, 4- or 16-pathway were unrelated to risk, although a borderline trend in risk was associated with high levels of 17-epiestriol. Conclusion Circulating estrogens and their metabolites were generally unrelated to CRC risk in postmenopausal women. Impact Additional studies are needed to understand how exogenous estrogen may prevent CRC PMID:26104910

  10. Synthesis of Linezolid Metabolites PNU-142300 and PNU-142586 toward the Exploration of Metabolite-Related Events.

    Science.gov (United States)

    Hanaya, Kengo; Matsumoto, Kazuaki; Yokoyama, Yuta; Kizu, Junko; Shoji, Mitsuru; Sugai, Takeshi

    2017-01-01

    Linezolid (1) is an oxazolidinone antibiotic that is partially metabolized in vivo via ring cleavage of its morpholine moiety to mainly form two metabolites, PNU-142300 (2) and PNU-142586 (3). It is supposed that accumulation of 2 and 3 in patients with renal insufficiency may cause thrombocytopenia, one of the adverse effects of linezolid. However, the poor availability of 2 and 3 has hindered further investigation of the clinical significance of the accumulation of these metabolites. In this paper, we synthesized metabolites 2 and 3 via a common synthetic intermediate, 4; this will encourage further exploration of events related to these metabolites and lead to improved clinical use of linezolid.

  11. Identification of metabolites of the tryptase inhibitor CRA-9249: observation of a metabolite derived from an unexpected hydroxylation pathway.

    Science.gov (United States)

    Yu, Walter; Dener, Jeffrey M; Dickman, Daniel A; Grothaus, Paul; Ling, Yun; Liu, Liang; Havel, Chris; Malesky, Kimberly; Mahajan, Tania; O'Brian, Colin; Shelton, Emma J; Sperandio, David; Tong, Zhiwei; Yee, Robert; Mordenti, Joyce J

    2006-08-01

    The metabolites of the tryptase inhibitor CRA-9249 were identified after exposure to liver microsomes. CRA-9249 was found to be degraded rapidly in liver microsomes from rabbit, dog, cynomolgus monkey, and human, and less rapidly in microsomes from rat. The key metabolites included cleavage of an aryl ether, in addition to an unexpected hydroxylation of the amide side chain adjacent to the amide nitrogen. The chemical structures of both metabolites were confirmed by synthesis and comparison to material isolated from the liver microsomes. Several suspected hydroxylated metabolites were also synthesized and analyzed as part of the structure identification process.

  12. Characterization of Urinary Phthalate Metabolites Among Custodians

    Science.gov (United States)

    Cavallari, Jennifer M.; Simcox, Nancy J.; Wakai, Sara; Lu, Chensheng; Garza, Jennifer L.; Cherniack, Martin

    2015-01-01

    Phthalates, a ubiquitous class of chemicals found in consumer, personal care, and cleaning products, have been linked to adverse health effects. Our goal was to characterize urinary phthalate metabolite concentrations and to identify work and nonwork sources among custodians using traditional cleaning chemicals and ‘green’ or environmentally preferable products (EPP). Sixty-eight custodians provided four urine samples on a workday (first void, before shift, end of shift, and before bedtime) and trained observers recorded cleaning tasks and types of products used (traditional, EPP, or disinfectant) hourly over the work shifts. Questionnaires were used to assess personal care product use. Four different phthalate metabolites [monoethyl phthalate (MEP), monomethyl phthalate (MMP), mono (2-ethylhexyl) phthalate (MEHP), and monobenzyl phthalate (MBzP)] were quantified using liquid chromatography mass spectrometry. Geometric means (GM) and 95% confidence intervals (95% CI) were calculated for creatinine-adjusted urinary phthalate concentrations. Mixed effects univariate and multivariate modeling, using a random intercept for each individual, was performed to identify predictors of phthalate metabolites including demographics, workplace factors, and personal care product use. Creatinine-adjusted urinary concentrations [GM (95% CI)] of MEP, MMP, MEHP, and MBzP were 107 (91.0–126), 2.69 (2.18–3.30), 6.93 (6.00–7.99), 8.79 (7.84–9.86) µg g−1, respectively. An increasing trend in phthalate concentrations from before to after shift was not observed. Creatinine-adjusted urinary MEP was significantly associated with frequency of traditional cleaning chemical intensity in the multivariate model after adjusting for potential confounding by demographics, workplace factors, and personal care product use. While numerous demographics, workplace factors, and personal care products were statistically significant univariate predictors of MMP, MEHP, and MBzP, few

  13. Circulating water pumps for nuclear power stations

    International Nuclear Information System (INIS)

    Satoh, Hiroshi; Ohmori, Tsuneaki

    1979-01-01

    Shortly, the nuclear power station with unit power output of 1100 MW will begin the operation, and the circulating water pumps manufactured recently are those of 2.4 to 4 m bore, 840 to 2170 m 3 /min discharge and 2100 to 5100 kW driving power. The circulating water pumps are one of important auxiliary machines, because if they fail, power generation capacity lowers immediately. Enormous quantity of cooling water is required to cool condensers, therefore in Japan, sea water is usually used. As siphon is formed in circulating water pipes, the total head of the pumps is not very high. The discharge of the pumps is determined so as to keep the temperature rise of discharged water lower than 7 deg. C. The quantity of cooling water for nuclear power generation is about 50% more as compared with thermal power generation because of the difference in steam conditions. The total head of the pumps is normally from 8 to 15 m. The circulating water pumps rarely stop after they started the operation, therefore it is economical to determine the motor power so that it can withstand 10% overload for a short period, instead of large power. At present, vertical shaft, oblique flow circulating water pumps are usually employed. Recently, movable blade pumps are adopted. The installation, construction and materials of the pumps and the problems are described. (Kako, I.)

  14. Cascade of circulations in fluid turbulence.

    Science.gov (United States)

    Eyink, Gregory L

    2006-12-01

    Kelvin's theorem on conservation of circulations is an essential ingredient of Taylor's theory of turbulent energy dissipation by the process of vortex-line stretching. In previous work, we have proposed a nonlinear mechanism for the breakdown of Kelvin's theorem in ideal turbulence at infinite Reynolds number. We develop here a detailed physical theory of this cascade of circulations. Our analysis is based upon an effective equation for large-scale coarse-grained velocity, which contains a turbulent-induced vortex force that can violate Kelvin's theorem. We show that singularities of sufficient strength, which are observed to exist in turbulent flow, can lead to nonvanishing dissipation of circulation for an arbitrarily small coarse-graining length in the effective equations. This result is an analog for circulation of Onsager's theorem on energy dissipation for singular Euler solutions. The physical mechanism of the breakdown of Kelvin's theorem is diffusion of lines of large-scale vorticity out of the advected loop. This phenomenon can be viewed as a classical analog of the Josephson-Anderson phase-slip phenomenon in superfluids due to quantized vortex lines. We show that the circulation cascade is local in scale and use this locality to develop concrete expressions for the turbulent vortex force by a multiscale gradient expansion. We discuss implications for Taylor's theory of turbulent dissipation and we point out some related cascade phenomena, in particular for magnetic flux in magnetohydrodynamic turbulence.

  15. Utilizing relative potency factors (RPF) and threshold of toxicological concern (TTC) concepts to assess hazard and human risk assessment profiles of environmental metabolites: a case study.

    Science.gov (United States)

    Terry, C; Rasoulpour, R J; Knowles, S; Billington, R

    2015-03-01

    There is currently no standard paradigm for hazard and human risk assessment of environmental metabolites for agrochemicals. Using an actual case study, solutions to challenges faced are described and used to propose a generic concept to address risk posed by metabolites to human safety. A novel approach - built on the foundation of predicted human exposures to metabolites in various compartments (such as food and water), the threshold of toxicological concern (TTC) and the concept of comparative toxicity - was developed for environmental metabolites of a new chemical, sulfoxaflor (X11422208). The ultimate aim was to address the human safety of the metabolites with the minimum number of in vivo studies, while at the same time, ensuring that human safety would be considered addressed on a global regulatory scale. The third component, comparative toxicity, was primarily designed to determine whether the metabolites had the same or similar toxicity profiles to their parent molecule, and also to one another. The ultimate goal was to establish whether the metabolites had the potential to cause key effects - such as cancer and developmental toxicity, based on mode-of-action (MoA) studies - and to develop a relative potency factor (RPF) compared to the parent molecule. Collectively, the work presented here describes the toxicology programme developed for sulfoxaflor and its metabolites, and how it might be used to address similar future challenges aimed at determining the relevance of the metabolites from a human hazard and risk perspective. Sulfoxaflor produced eight environmental metabolites at varying concentrations in various compartments - soil, water, crops and livestock. The MoA for the primary effects of the parent molecule were elucidated in detail and a series of in silico, in vitro, and/or in vivo experiments were conducted on the environmental metabolites to assess relative potency of their toxicity profiles when compared to the parent. The primary metabolite

  16. Circulation as Assessment: Collection Development Policies Evaluated in Terms of Circulation at a Small Academic Library.

    Science.gov (United States)

    Dinkins, Debbi

    2003-01-01

    Discusses the use of academic library circulation statistics to assess whether user needs are being met and describes a study at Stetson University that investigated collection development practices by comparing circulation statistics for books selected by faculty in support of departmental curricula with those of librarian selections. (Author/LRW)

  17. Simulation of branched serial first-order decay of atrazine and metabolites in adapted and nonadapted soils

    Science.gov (United States)

    Webb, Richard M.; Sandstrom, Mark W.; Jason L. Krutz,; Dale L. Shaner,

    2011-01-01

    In the present study a branched serial first-order decay (BSFOD) model is presented and used to derive transformation rates describing the decay of a common herbicide, atrazine, and its metabolites observed in unsaturated soils adapted to previous atrazine applications and in soils with no history of atrazine applications. Calibration of BSFOD models for soils throughout the country can reduce the uncertainty, relative to that of traditional models, in predicting the fate and transport of pesticides and their metabolites and thus support improved agricultural management schemes for reducing threats to the environment. Results from application of the BSFOD model to better understand the degradation of atrazine supports two previously reported conclusions: atrazine (6-chloro-N-ethyl-N′-(1-methylethyl)-1,3,5-triazine-2,4-diamine) and its primary metabolites are less persistent in adapted soils than in nonadapted soils; and hydroxyatrazine was the dominant primary metabolite in most of the soils tested. In addition, a method to simulate BSFOD in a one-dimensional solute-transport unsaturated zone model is also presented.

  18. Encapsulates for Food Bioconversions and Metabolite Production

    Science.gov (United States)

    Breguet, Véronique; Vojinovic, Vojislav; Marison, Ian W.

    The control of production costs in the food industry must be very strict as a result of the relatively low added value of food products. Since a wide variety of enzymes and/or cells are employed in the food industry for starch processing, cheese making, food preservation, lipid hydrolysis and other applications, immobilization of the cells and/or enzymes has been recognized as an attractive approach to improving food processes while minimizing costs. This is due to the fact that biocatalyst immobilization allows for easier separation/purification of the product and reutilization of the biocatalyst. The advantages of the use of immobilized systems are many, and they have a special relevance in the area of food technology, especially because industrial processes using immobilized biosystems are usually characterized by lower capital/energy costs and better logistics. The main applications of immobilization, related to the major processes of food bioconversions and metabolite production, will be described and discussed in this chapter.

  19. Formation of reactive metabolites from benzene

    International Nuclear Information System (INIS)

    Snyder, R.; Jowa, L.; Witz, G.; Kalf, G.; Rushmore, T.

    1986-01-01

    Rat liver mitoplasts were incubated first with [ 3 H]dGTP, to form DNA labeled in G, and then with [ 14 C]benzene. The DNA was isolated and upon isopycnic density gradient centrifugation in CsCl yielded a single fraction of DNA labeled with both [ 3 H] and [ 14 C]. These data are consistent with the covalent binding of one or more metabolites of benzene to DNA. The DNA was enzymatically hydrolyzed to deoxynucleosides and chromatographed to reveal at least seven deoxyguanosine adducts. Further studies with labeled deoxyadenine revealed one adduct on deoxyadenine. [ 3 H]Deoxyguanosine was reacted with [ 14 C]hydroquinone or benzoquinone. The product was characterized using uv, fluorescence, mass and NMR spectroscopy. A proposed structure is described. (orig.)

  20. Engineering of secondary metabolite production in streptomycetes

    DEFF Research Database (Denmark)

    Robertsen, Helene Lunde; Gram, Lone

    Streptomycetes are known for their ability to produce a range of different secondary metabolites, including antibiotics, immunosuppressive, anti-fungals, and anti-cancer compounds. Of these compounds, antibiotics play an important role in the clinics for treatment of both mild and severe bacterial...... the computational prediction of suitable 20 bp protospacers for the single guide RNAs and a USER-cloning method for construction of the CRISPR plasmids. Additional improvement to the system was achieved through the development of an optimised USER assembly workflow for cheaper and faster plasmid construction....... The workflow was verified by manual knock-down of two biosynthetic gene clusters in model organism Streptomyces coelicolor A3(2), which confirmed the applicability of the system. A second part of the thesis was devoted to engineering of Streptomyces collinus Tü 365, which is a known producer of the narrow...

  1. Serum concentrations of phthalate metabolites are related to abdominal fat distribution two years later in elderly women

    Directory of Open Access Journals (Sweden)

    Lind P Monica

    2012-04-01

    Full Text Available Abstract Background Phthalates, commonly used to soften plastic goods, are known PPAR-agonists affecting lipid metabolism and adipocytes in the experimental setting. We evaluated if circulating concentrations of phthalates were related to different indices of obesity using data from the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS study. Data from both dual-energy X-ray absorptiometry (DXA and abdominal magnetic resonance imaging (MRI were used. Methods 1,016 subjects aged 70 years were investigated in the PIVUS study. Four phthalate metabolites were detected in the serum of almost all subjects (> 96% by an API 4000 liquid chromatograph/tandem mass spectrometer. Abdominal MRI was performed in a representative subsample of 287 subjects (28%, and a dual-energy X-ray absorptiometry (DXA-scan was obtained in 890 (88% of the subjects two year following the phthalate measurements. Results In women, circulating concentrations of mono-isobutyl phthalate (MiBP were positively related to waist circumference, total fat mass and trunk fat mass by DXA, as well as to subcutaneous adipose tissue by MRI following adjustment for serum cholesterol and triglycerides, education, smoking and exercise habits (all p Conclusions The present evaluation shows that especially the phthalate metabolite MiBP was related to increased fat amount in the subcutaneous abdominal region in women measured by DXA and MRI two years later.

  2. Experimental study of the natural circulation phenomena

    International Nuclear Information System (INIS)

    Sabundjian, Gaiane; Andrade, Delvonei Alves de; Umbehaun, Pedro E.; Torres, Walmir M.; Castro, Alfredo Jose Alvim de; Belchior Junior, Antonio; Rocha, Ricardo Takeshi Vieira da; Damy, Osvaldo Luiz de Almeida; Torres, Eduardo

    2006-01-01

    The objective of this paper is to study the natural circulation in experimental loops and extend the results to nuclear facilities. New generation of compact nuclear power plants use the natural circulation as cooling and residual heat removal systems in case of accidents or shutdown. Lately the interest in this phenomenon, by scientific community, has increased. The experimental loop, described in this paper, was assembled at Escola Politecnica - USP at the Chemical Engineering Department. It is the goal to generate information to help with the understanding of the one and two phase natural circulation phenomena. Some experiments were performed with different levels of heat power and different flow of the cooling water at the secondary circuit. The data generated from these experiments are going to be used to validate some computational thermal hydraulic codes. Experimental results for one and two phase regimes are presented as well as the proposed model to simulate the flow regimes with the RELAP5 code. (author)

  3. Systems engineering requirements impacting MHTGR circulator design

    International Nuclear Information System (INIS)

    Chi, H.W.; Baccaglini, G.M.; Potter, R.C.; Shenoy, A.S.

    1988-01-01

    At the initiation of the MHTGR program, an important task involved translating the plant users' requirements into design conditions. This was particularly true in the case of the heat transport and shutdown cooling systems since these embody many components. This paper addresses the two helium circulators in these systems. An integrated approach is being used in the development of design and design documentation for the MHTGR plant. It is an organized and systematic development of plant functions and requirements, determined by top-down design, performance, and cost trade-off studies and analyses, to define the overall plant systems, subsystems, components, and human actions. These studies, that led to the identification of the major design parameters for the two circulators, are discussed in this paper. This includes the performance information, steady state and transient data, and the various interface requirements. The design of the circulators used in the MHTGR is presented. (author). 1 ref., 17 figs

  4. Circulating microRNAs in breast cancer

    DEFF Research Database (Denmark)

    Hamam, Rimi; Hamam, Dana; Alsaleh, Khalid A

    2017-01-01

    Effective management of breast cancer depends on early diagnosis and proper monitoring of patients' response to therapy. However, these goals are difficult to achieve because of the lack of sensitive and specific biomarkers for early detection and for disease monitoring. Accumulating evidence in ...... circulating miRNAs as diagnostic, prognostic or predictive biomarkers in breast cancer management.......Effective management of breast cancer depends on early diagnosis and proper monitoring of patients' response to therapy. However, these goals are difficult to achieve because of the lack of sensitive and specific biomarkers for early detection and for disease monitoring. Accumulating evidence...... in the past several years has highlighted the potential use of peripheral blood circulating nucleic acids such as DNA, mRNA and micro (mi)RNA in breast cancer diagnosis, prognosis and for monitoring response to anticancer therapy. Among these, circulating miRNA is increasingly recognized as a promising...

  5. Adjustable speed drives improve circulating water system

    International Nuclear Information System (INIS)

    Dent, R.A.; Dicic, Z.

    1994-01-01

    This paper illustrates the integration of electrical and mechanical engineering requirements to produce a solution to past problems and future operating demands. The application of adjustable speed drives in the modifications of the circulating water system at Indian Point No. 3 Nuclear Power Plant provided increased operating flexibility, efficiency and avoided otherwise costly renovations to the plant electrical systems. Rectification of the original inadequate design of the circulating water system, in addition to maximizing plant efficiency consistent with environmental considerations, formed the basis for this modification. This entailed replacement of all six circulating water pumps and motors and physical modifications to the intake system. This paper details the methodology used in this engineering task. The new system was installed successfully and has been operating reliably and economically for the past eight years

  6. Methionine Metabolites in Patients With Sepsis.

    Science.gov (United States)

    Wexler, Orren; Gough, Michael S; Morgan, Mary Anne M; Mack, Cynthia M; Apostolakos, Michael J; Doolin, Kathleen P; Mooney, Robert A; Arning, Erland; Bottiglieri, Teodoro; Pietropaoli, Anthony P

    2018-01-01

    Sepsis is characterized by microvascular dysfunction and thrombophilia. Several methionine metabolites may be relevant to this sepsis pathophysiology. S-adenosylmethionine (SAM) serves as the methyl donor for trans-methylation reactions. S-adenosylhomocysteine (SAH) is the by-product of these reactions and serves as the precursor to homocysteine. Relationships between plasma total homocysteine concentrations (tHcy) and vascular disease and thrombosis are firmly established. We hypothesized that SAM, SAH, and tHcy levels are elevated in patients with sepsis and associated with mortality. This was a combined case-control and prospective cohort study consisting of 109 patients with sepsis and 50 control participants without acute illness. The study was conducted in the medical and surgical intensive care units of the University of Rochester Medical Center. Methionine, SAM, SAH, and tHcy concentrations were compared in patients with sepsis versus control participants and in sepsis survivors versus nonsurvivors. Patients with sepsis had significantly higher plasma SAM and SAH concentrations than control participants (SAM: 164 [107-227] vs73 [59-87 nM], P sepsis patients compared to healthy control participants (4 [2-6]) vs 7 [5-9] μM; P = .04). In multivariable analysis, quartiles of SAM, SAH, and tHcy were independently associated with sepsis ( P = .006, P = .05, and P Sepsis nonsurvivors had significantly higher plasma SAM and SAH concentrations than survivors (SAM: 223 [125-260] vs 136 [96-187] nM; P = .01; SAH: 139 [81-197] vs 86 [55-130] nM, P = .006). Plasma tHcy levels were similar in survivors vs nonsurvivors. The associations between SAM or SAH and hospital mortality were no longer significant after adjusting for renal dysfunction. Methionine metabolite concentrations are abnormal in sepsis and linked with clinical outcomes. Further study is required to determine whether these abnormalities have pathophysiologic significance.

  7. A Latex Metabolite Benefits Plant Fitness under Root Herbivore Attack

    NARCIS (Netherlands)

    Huber, M.; Epping, Janina; Schulze Gronover, C.; Fricke, Julia; Aziz, Zohra; Brillatz, Théo; Swyers, Michael; Kollner, T.G.; Vogel, H.; Hammerbacher, Almuth; Triebwasser-Freese, Daniella; Robert, Christelle A.M.; Verhoeven, K.J.F.; Preite, V.; Gershenzon, J.; Erb, M.

    2016-01-01

    Plants produce large amounts of secondary metabolites in their shoots and roots and store them in specialized secretory structures. Although secondary metabolites and their secretory structures are commonly assumed to have a defensive function, evidence that they benefit plant fitness under

  8. Pharmacokinetics of ifosfamide and some metabolites in children

    NARCIS (Netherlands)

    Kaijser, G. P.; de Kraker, J.; Bult, A.; Underberg, W. J.; Beijnen, J. H.

    1998-01-01

    The pharmacokinetics of ifosfamide and some metabolites in children was investigated. The patients received various doses of ifosfamide, mostly by continuous infusion, over several days. The penetration of ifosfamide and its metabolites into the cerebrospinal fluid was also studied in four cases.

  9. Effect of metabolites produced by Trichoderma species against ...

    African Journals Online (AJOL)

    Metabolites released from Trichoderma viride, T. polysporum, T. hamatum and T. aureoviride were tested in culture medium against Ceratocystis paradoxa, which causes black seed rot in oil palm sprouted seeds. The Trichoderma metabolites had similar fungistatic effects on the growth of C. paradoxa except those from T.

  10. Prototype of an intertwined secondary-metabolite supercluster

    Science.gov (United States)

    Phillipp Wiemann; Chun-Jun. Guo; Jonathan M. Palmer; Relebohile Sekonyela; Clay C.C. Wang; Nancy P. Keller

    2013-01-01

    The hallmark trait of fungal secondary-metabolite gene clusters is well established, consisting of contiguous enzymatic and often regulatory gene(s) devoted to the production of a metabolite of a specific chemical class. Unexpectedly, we have found a deviation from this motif in a subtelomeric region of Aspergillus fumigatus. This region, under the...

  11. Metabolite characterization in serum samples from normal healthy ...

    African Journals Online (AJOL)

    Metabolite characterization in serum samples from normal healthy human subjects by 1H and 13C NMR spectroscopy. D Misra, U Bajpai. Abstract. One and two dimensional NMR spectroscopy has been employed to characterize the various metabolites of serum control healthy samples. Two dimensional heteronuclear ...

  12. UV-guided isolation of fungal metabolites by HSCCC

    DEFF Research Database (Denmark)

    Dalsgaard, P.W.; Nielsen, K.F.; Larsen, Thomas Ostenfeld

    2005-01-01

    Analytical standardised reversed phase liquid chromatography (RPLC) data can be helpful in finding a suitable solvent combination for isolation of fungal metabolites by high-speed counter current chromatography. Analysis of the distribution coefficient (K-D) of fungal metabolites in a series...... peptides from a crude fungal extract....

  13. Aspergillus flavus secondary metabolites: more than just aflatoxins

    Science.gov (United States)

    Aspergillus flavus is best known for producing the family of potent carcinogenic secondary metabolites known as aflatoxins. However, this opportunistic plant and animal pathogen also produces numerous other secondary metabolites, many of which have also been shown to be toxic. While about forty of t...

  14. Synthesis of an Albendazole Metabolite: Characterization and HPLC Determination

    Science.gov (United States)

    Mahler, Graciela; Davyt, Danilo; Gordon, Sandra; Incerti, Marcelo; Nunez, Ivana; Pezaroglo, Horacio; Scarone, Laura; Serra, Gloria; Silvera, Mauricio; Manta, Eduardo

    2008-01-01

    In this laboratory activity, students are introduced to the synthesis of an albendazole metabolite obtained by a sulfide oxidation reaction. Albendazole as well as its metabolite, albendazole sulfoxide, are used as anthelmintic drugs. The oxidation reagent is H[subscript 2]O[subscript 2] in acetic acid. The reaction is environmental friendly,…

  15. Assessment of CATHARE2 V1.5qR6 using the experimental data of BETHSY natural circulation tests

    International Nuclear Information System (INIS)

    Huang Yanping; Jia Dounan

    2003-01-01

    The assessment of CATHARE2 V1.5qR6 is carried out against the experimental data of BETHSY natural circulation test-4. 1a-TC. Results show that the experimental process under single phase natural circulation can be predicted very well by CATHARE2 V1.5qR6, the primary mass inventory at the transition points from single phase natural circulation to two-phase natural circulation and from two-phase natural circulation to reflux condensation mode are also predicted correctly. The predicted results for thermohydraulic parameters of two-phase natural circulation and reflux condensation mode are not so good. Generally speaking, the prediction capability of CATHARE2 V1.5 for strong and two-phase flow process should be improved further in future

  16. Natural circulation in a scaled PWR integral test facility

    International Nuclear Information System (INIS)

    Kiang, R.L.; Jeuck, P.R. III

    1987-01-01

    Natural circulation is an important mechanism for cooling a nuclear power plant under abnormal operating conditions. To study natural circulation, we modeled a type of pressurized water reactor (PWR) that incorporates once-through steam generators. We conducted tests of single-phase natural circulations, two-phase natural circulations, and a boiler condenser mode. Because of complex geometry, the natural circulations observed in this facility exhibit some phenomena not commonly seen in a simple thermosyphon loop

  17. Fort St. Vrain circulator operating experience

    Energy Technology Data Exchange (ETDEWEB)

    Brey, H. L.

    1988-08-15

    Fort St. Vrain, on the system of Public Service Company of Colorado, is the only high-temperature gas-cooled power reactor in the United States. Four helium circulators are utilized in this plant to transfer heat from the reactor to the steam generators. These unique machines have a single stage axial flow helium compressor driven by a single stage steam turbine. A single stage water driven (pelton wheel) turbine is the back-up drive utilizing either feed water, condensate, or fire water as the driving fluid. Developmental testing of the circulators was accomplished prior to installation into Fort St. Vrain. A combined machine operating history of approximately 250,000 hours has shown these machines to be of conservative design and proven mechanical integrity. However, many problems have been encountered in operating the complex auxiliaries which are necessary for successful circulator and plant operation. It has been 15 years since initial installation of the circulators occurred at Fort St. Vrain. During this time, a number of significant issues had to be resolved dealing specifically with machine performance. These events include cavitation damage of the pelton wheels during the initial plant hot functional testing, cracks in the water turbine buckets and cervic coupling, static shutdown seal bellows failure, and, most recently, degradation of components within the steam drive assembly. Unreliable operation particularly with the circulator auxiliaries has been a focus of attention by Public Service Company of Colorado. Actions to replace or significantly modify the existing circulators and their auxiliaries are currently awaiting decisions concerning the long-term future of the Fort St. Vrain plant. (author). 10 refs, 7 figs, 2 tabs.

  18. Fort St. Vrain circulator operating experience

    International Nuclear Information System (INIS)

    Brey, H.L.

    1988-01-01

    Fort St. Vrain, on the system of Public Service Company of Colorado, is the only high-temperature gas-cooled power reactor in the United States. Four helium circulators are utilized in this plant to transfer heat from the reactor to the steam generators. These unique machines have a single stage axial flow helium compressor driven by a single stage steam turbine. A single stage water driven (pelton wheel) turbine is the back-up drive utilizing either feed water, condensate, or fire water as the driving fluid. Developmental testing of the circulators was accomplished prior to installation into Fort St. Vrain. A combined machine operating history of approximately 250,000 hours has shown these machines to be of conservative design and proven mechanical integrity. However, many problems have been encountered in operating the complex auxiliaries which are necessary for successful circulator and plant operation. It has been 15 years since initial installation of the circulators occurred at Fort St. Vrain. During this time, a number of significant issues had to be resolved dealing specifically with machine performance. These events include cavitation damage of the pelton wheels during the initial plant hot functional testing, cracks in the water turbine buckets and cervic coupling, static shutdown seal bellows failure, and, most recently, degradation of components within the steam drive assembly. Unreliable operation particularly with the circulator auxiliaries has been a focus of attention by Public Service Company of Colorado. Actions to replace or significantly modify the existing circulators and their auxiliaries are currently awaiting decisions concerning the long-term future of the Fort St. Vrain plant. (author). 10 refs, 7 figs, 2 tabs

  19. Quenching phenomena in natural circulation loop

    International Nuclear Information System (INIS)

    Umekawa, Hisashi; Ozawa, Mamoru; Ishida, Naoki

    1995-01-01

    Quenching phenomena has been investigated experimentally using circulation loop of liquid nitrogen. During the quenching under natural circulation, the heat transfer mode changes from film boiling to nucleate boiling, and at the same time flux changes with time depending on the vapor generation rate and related two-phase flow characteristics. Moreover, density wave oscillations occur under a certain operating condition, which is closely related to the dynamic behavior of the cooling curve. The experimental results indicates that the occurrence of the density wave oscillation induces the deterioration of effective cooling of the heat surface in the film and the transition boiling regions, which results in the decrease in the quenching velocity

  20. Labour circulation and the urban labour process.

    Science.gov (United States)

    Standing, G

    1986-01-01

    The author investigates aspects of labor circulation, which he defines as "temporary movement between geographical areas for work or in search of work....[He attempts to determine] what roles have been played by labour circulation in the development of urban-industrial labour forces in the transition to industrial capitalism." Factors considered include the exploitation and oppression of labor migrants; the industrial-urban labor reserve; urban socioeconomic stratification and discrimination by age, sex, or race; the division of labor; and policy options. excerpt

  1. An elementary model of money circulation

    Science.gov (United States)

    Pokrovskii, Vladimir N.; Schinckus, Christophe

    2016-12-01

    This paper investigates money circulation for a system, consisting of a production system, the government, a central bank, commercial banks and many customers of the commercial banks. A set of equations for the system is written; the theory determines the main features of interaction between production and money circulation. Investigation of the equations in a steady-state situation reveals some relationship among output of the production system and monetary variables. The relation of quantity theory of money is confirmed, whereas a new concept of the efficiency of the system is introduced.

  2. Engineering Judgment and Natural Circulation Calculations

    International Nuclear Information System (INIS)

    Ferreri, J.C.; Ferreri, J.C.

    2011-01-01

    The analysis performed to establish the validity of computer code results in the particular field of natural circulation flow stability calculations is presented in the light of usual engineering practice. The effects of discretization and closure correlations are discussed and some hints to avoid undesired mistakes in the evaluations performed are given. Additionally, the results are presented for an experiment relevant to the way in which a (small) number of skilled, nuclear safety analysts and researchers react when facing the solution of a natural circulation problem. These results may be also framed in the concept of Engineering Judgment and are potentially useful for Knowledge Management activities.

  3. First circulating beam in the AA

    CERN Multimedia

    CERN PhotoLab

    1980-01-01

    On 3 July 1980, two years after project authorization, beam circulated for the first time in the AA. It was a 3.56 GeV/c proton test beam. We see an expecting crowd, minutes before the happy event. The persons are too numerous to name them all, but the 3 most prominent ones are at the centre (left to right): Roy Billinge (Joint AA Project Leader, with his hand on the control box), Eifionydd Jones (white shirt), Simon van der Meer (spiritus rector and Joint AA Project Leader). The first antiprotons were injected, made to circulate and cooled soon after, on 14 July 1980.

  4. Quenching phenomena in natural circulation loop

    Energy Technology Data Exchange (ETDEWEB)

    Umekawa, Hisashi; Ozawa, Mamoru [Kansai Univ., Osaka (Japan); Ishida, Naoki [Daihatsu Motor Company, Osaka (Japan)

    1995-09-01

    Quenching phenomena has been investigated experimentally using circulation loop of liquid nitrogen. During the quenching under natural circulation, the heat transfer mode changes from film boiling to nucleate boiling, and at the same time flux changes with time depending on the vapor generation rate and related two-phase flow characteristics. Moreover, density wave oscillations occur under a certain operating condition, which is closely related to the dynamic behavior of the cooling curve. The experimental results indicates that the occurrence of the density wave oscillation induces the deterioration of effective cooling of the heat surface in the film and the transition boiling regions, which results in the decrease in the quenching velocity.

  5. Montane ecosystem productivity responds more to global circulation patterns than climatic trends

    Science.gov (United States)

    Desai, A. R.; Wohlfahrt, G.; Zeeman, M. J.; Katata, G.; Eugster, W.; Montagnani, L.; Gianelle, D.; Mauder, M.; Schmid, H.-P.

    2016-02-01

    Regional ecosystem productivity is highly sensitive to inter-annual climate variability, both within and outside the primary carbon uptake period. However, Earth system models lack sufficient spatial scales and ecosystem processes to resolve how these processes may change in a warming climate. Here, we show, how for the European Alps, mid-latitude Atlantic ocean winter circulation anomalies drive high-altitude summer forest and grassland productivity, through feedbacks among orographic wind circulation patterns, snowfall, winter and spring temperatures, and vegetation activity. Therefore, to understand future global climate change influence to regional ecosystem productivity, Earth systems models need to focus on improvements towards topographic downscaling of changes in regional atmospheric circulation patterns and to lagged responses in vegetation dynamics to non-growing season climate anomalies.

  6. Capacitance sensor for void fraction measurement in a natural circulation refrigeration circuit

    International Nuclear Information System (INIS)

    Rocha, Marcelo S.; Cabral, Eduardo L.L.; Simoes-Moreira, Jose R.

    2009-01-01

    Natural circulation is widely used in nuclear reactors for residual heat refrigeration. In this work, a conductance probe is designed and constructed to measure the instantaneous bulk void fraction in a vertical tube section. This probe is installed in a natural circulation refrigeration loop designed to simulate a nuclear reactor primary refrigeration circuit. During the operation of the natural circulation loop several gas-liquid flow patterns are observed, including oscillatory flow. The instantaneous signal generated by the capacitance probe allows the calculation of the two-phase flow void fraction. The void fraction obtained by the probe will be compared with the theoretical void fraction calculated by the computational program RELAP5/MOD3.2.2 gamma. The probe design and electronics, as well as the previous results obtained are presented and discussed. (author)

  7. Montane ecosystem productivity responds more to global circulation patterns than climatic trends

    International Nuclear Information System (INIS)

    Desai, A R; Wohlfahrt, G; Zeeman, M J; Katata, G; Mauder, M; Schmid, H-P; Eugster, W; Montagnani, L; Gianelle, D

    2016-01-01

    Regional ecosystem productivity is highly sensitive to inter-annual climate variability, both within and outside the primary carbon uptake period. However, Earth system models lack sufficient spatial scales and ecosystem processes to resolve how these processes may change in a warming climate. Here, we show, how for the European Alps, mid-latitude Atlantic ocean winter circulation anomalies drive high-altitude summer forest and grassland productivity, through feedbacks among orographic wind circulation patterns, snowfall, winter and spring temperatures, and vegetation activity. Therefore, to understand future global climate change influence to regional ecosystem productivity, Earth systems models need to focus on improvements towards topographic downscaling of changes in regional atmospheric circulation patterns and to lagged responses in vegetation dynamics to non-growing season climate anomalies. (letter)

  8. Two-phase natural circulation experiments in a pressurized water loop with CANDU geometry

    International Nuclear Information System (INIS)

    Ardron, K.H.; Krishnan, V.S.; McGee, G.R.; Anderson, J.W.D.; Hawley, E.H.

    1984-07-01

    To provide information on two-phase natural circulation in a CANDU-type coolant circuit a series of tests has been performed in the RD-12 loop at the Whiteshell Nuclear Research Establishment. RD-12 is a 10-MPa pressurized-water loop containing two active boilers, two pumps, and two, or four, heated horizontal channels arranged in a symmetrical figure-of-eight configuration characteristic of the CANDU reactor primary heat-transport system. In the tests, single-phase natural circulation was established in the loop and void was introduced by controlled draining, with the surge tank (pressurizer) valved out of the system. The paper reviews the experimental results obtained and describes the evolution of natural circulation flow in particular cases as voidage is progressively increased. The stability behaviour is discussed briefly with reference to a simple stability model

  9. Natural circulation and stratification in the various passive safety systems of the SWR 1000

    International Nuclear Information System (INIS)

    Meseth, J.

    2002-01-01

    In some of the passive safety systems of Siemens' SWR 1000 boiling water reactor (i.e. the emergency condensers and containment cooling condensers), natural circulation is the main effect on both the primary and secondary sides by which optimum system efficiency is achieved. Other passive safety systems of the SWR 1000 require natural circulation on the secondary side only (condensation of steam discharged by the safety and relief valves; cooling of the Reactor Pressure Vessel (RPV) by flooding from the outside in case of core melt), while still other systems require stratification to be effective (i.e. the passive pressure pulse transmitters and steam-driven scram tanks). Complex natural circulation and stratification can take place simultaneously if fluids with different densities are enclosed in a single volume (in a core melt accident, for example, the nitrogen, steam and hydrogen in the containment). Related problems and the solutions thereto planned for the SWR 1000 are reported from the designer's viewpoint. (author)

  10. Steam generator and circulator model for the HELAP code

    International Nuclear Information System (INIS)

    Ludewig, H.

    1975-07-01

    An outline is presented of the work carried out in the 1974 fiscal year on the GCFBR safety research project consisting of the development of improved steam generator and circulator (steam turbine driven helium compressor) models which will eventually be inserted in the HELAP (1) code. Furthermore, a code was developed which will be used to generate steady state input for the primary and secondary sides of the steam generator. The following conclusions and suggestions for further work are made: (1) The steam-generator and circulator model are consistent with the volume and junction layout used in HELAP, (2) with minor changes these models, when incorporated in HELAP, could be used to simulate a direct cycle plant, (3) an explicit control valve model is still to be developed and would be very desirable to control the flow to the turbine during a transient (initially this flow will be controlled by using the existing check valve model); (4) the friction factor in the laminar flow region is computed inaccurately, this might cause significant errors in loss-of-flow accidents; and (5) it is felt that HELAP will still use a large amount of computer time and will thus be limited to design basis accidents without scram or loss of flow transients with and without scram. Finally it may also be used as a test bed for the development of prototype component models which would be incorporated in a more sophisticated system code, developed specifically for GCFBR's

  11. Experimental observations of natural circulation flow in the NSTF

    Energy Technology Data Exchange (ETDEWEB)

    Lisowski, Darius D., E-mail: dlisowski@anl.gov; Kraus, Adam R.; Bucknor, Matthew D.; Hu, Rui; Farmer, Mitch T.

    2016-09-15

    A 1/2 scale test facility has been constructed at Argonne National Laboratory to study the heat removal performance and natural circulation flow patterns in a Reactor Cavity Cooling System (RCCS). Our test facility, the Natural convection Shutdown heat removal Test Facility (NSTF), supports the broader goal of developing an inherently safe and fully passive ex-vessel decay heat removal for advanced reactor designs. The project, initiated in 2010 to support the Advanced Reactor Technologies (ART), Small Modular Reactor (SMR), and Next Generation Nuclear Plant (NGNP) programs, has been conducting experimental operations since early 2014. The following paper provides a summary of some primary design features of the 26-m tall test facility along with a description of the data acquisition suite that guides our experimental practices. Specifics of the distributed fiber optic temperature measurements will be discussed, which introduces an unparalleled level of data density that has never before been implemented in a large scale natural circulation test facility. Results from our test series will then be presented, which provide insight into the thermal hydraulic behavior at steady-state and transient conditions for varying heat flux levels and exhaust chimney configuration states.

  12. A randomized trial of social media from Circulation.

    Science.gov (United States)

    Fox, Caroline S; Bonaca, Marc A; Ryan, John J; Massaro, Joseph M; Barry, Karen; Loscalzo, Joseph

    2015-01-06

    Medical journals use social media to distribute the findings of published articles. Whether social media exposure to original articles improves article impact metrics is uncertain. Articles were randomized to receive targeted social media exposure from Circulation, including postings on the journal's Facebook and Twitter feeds. The primary end point was 30-day article page views. We conducted an intention-to-treat analysis comparing article page views by the Wilcoxon Rank sum test between articles randomized to social media as compared with those in the control group, which received no social media from Circulation. Prespecified subgroups included article type (population/clinical/basic), US versus non-US corresponding author, and whether the article received an editorial. Overall, 243 articles were randomized: 121 in the social media arm and 122 in the control arm. There was no difference in median 30-day page views (409 [social media] versus 392 [control], P=0.80). No differences were observed by article type (clinical, population, or basic science; P=0.19), whether an article had an editorial (P=0.87), or whether the corresponding author was from the United States (P=0.73). A social media strategy for a cardiovascular journal did not increase the number of times an article was viewed. Further research is necessary to understand and quantify the ways in which social media can increase the impact of published cardiovascular research. © 2014 American Heart Association, Inc.

  13. Novel urinary metabolite of d-delta-tocopherol in rats

    International Nuclear Information System (INIS)

    Chiku, S.; Hamamura, K.; Nakamura, T.

    1984-01-01

    A novel metabolite of d-delta-tocopherol was isolated from the urine of rats given d-3,4-[ 3 H 2 ]-delta-tocopherol intravenously. The metabolite was collected from the urine of rats given d-delta-tocopherol in the same manner as that of the labeled compound. It was found that the metabolites consisted of sulfate conjugates. The portion of the major metabolite released with sulfatase was determined to be 2,8-dimethyl-2-(2'-carboxyethyl)-6-chromanol by infrared spectra, nuclear magnetic resonance spectra, and mass spectra. The proposed structure was confirmed by comparing the analytical results with those of a synthetically derived compound. As a result of the structural elucidation of this novel metabolite, a pathway for the biological transformation of delta-tocopherol is proposed which is different from that of alpha-tocopherol. A characteristic feature of the pathway is the absence of any opening of the chroman ring throughout the sequence

  14. Loss of metabolites from monkey striatum during PET with FDOPA

    DEFF Research Database (Denmark)

    Cumming, P; Munk, O L; Doudet, D

    2001-01-01

    diffusion of [(18)F]fluorodopamine metabolites from brain. Consequently, time-radioactivity recordings of striatum are progressively influenced by metabolite loss. In linear analyses, the net blood-brain clearance of FDOPA (K(D)(i), ml g(-1) min(-1)) can be corrected for this loss by the elimination rate...... constant k(Lin)(cl) (min(-1)). Similarly, the DOPA decarboxylation rate constant (k(D)(3), min(-1)) calculated by compartmental analysis can also be corrected for metabolite loss by the elimination rate constant k(DA)(9) (min(-1)). To compare the two methods, we calculated the two elimination rate...... of the estimate was substantially improved upon correction for metabolite loss. The rate constants for metabolite loss were higher in MPTP-lesioned monkey striatum than in normal striatum. The high correlation between individual estimates of k(Lin)(cl) and k(DA)(9) suggests that both rate constants reveal loss...

  15. Yeast synthetic biology for high-value metabolites.

    Science.gov (United States)

    Dai, Zhubo; Liu, Yi; Guo, Juan; Huang, Luqi; Zhang, Xueli

    2015-02-01

    Traditionally, high-value metabolites have been produced through direct extraction from natural biological sources which are inefficient, given the low abundance of these compounds. On the other hand, these high-value metabolites are usually difficult to be synthesized chemically, due to their complex structures. In the last few years, the discovery of genes involved in the synthetic pathways of these metabolites, combined with advances in synthetic biology tools, has allowed the construction of increasing numbers of yeast cell factories for production of these metabolites from renewable biomass. This review summarizes recent advances in synthetic biology in terms of the use of yeasts as microbial hosts for the identification of the pathways involved in the synthesis, as well as for the production of high-value metabolites. © FEMS 2015. All rights reserved. For permissions, please e-mail: journals.permission@oup.com.

  16. (1) H-MRS processing parameters affect metabolite quantification

    DEFF Research Database (Denmark)

    Bhogal, Alex A; Schür, Remmelt R; Houtepen, Lotte C

    2017-01-01

    investigated the influence of model parameters and spectral quantification software on fitted metabolite concentration values. Sixty spectra in 30 individuals (repeated measures) were acquired using a 7-T MRI scanner. Data were processed by four independent research groups with the freedom to choose their own...... + NAAG/Cr + PCr and Glu/Cr + PCr, respectively. Metabolite quantification using identical (1) H-MRS data was influenced by processing parameters, basis sets and software choice. Locally preferred processing choices affected metabolite quantification, even when using identical software. Our results......Proton magnetic resonance spectroscopy ((1) H-MRS) can be used to quantify in vivo metabolite levels, such as lactate, γ-aminobutyric acid (GABA) and glutamate (Glu). However, there are considerable analysis choices which can alter the accuracy or precision of (1) H-MRS metabolite quantification...

  17. Aerobic biodegradation of a nonylphenol polyethoxylate and toxicity of the biodegradation metabolites.

    Science.gov (United States)

    Jurado, Encarnación; Fernández-Serrano, Mercedes; Núñez-Olea, Josefa; Lechuga, Manuela

    2009-09-01

    In this paper a study was made of the biodegradation of a non-ionic surfactant, a nonylphenol polyethoxylate, in biodegradability tests by monitoring the residual surfactant matter. The influence of the concentration on the extent of primary biodegradation, the toxicity of biodegradation metabolites, and the kinetics of degradation were also determined. The primary biodegradation was studied at different initial concentrations: 5, 25 and 50 mg/L, (at sub-and supra-critical micelle concentration). The NPEO used in this study can be considered biodegradable since the primary biodegradation had already taken place (a biodegradation greater than 80% was found for the different initial concentration tested). The initial concentration affected the shape of the resulting curve, the mean biodegradation rate and the percentage of biodegradation reached (99% in less than 8 days at 5 mg/L, 98% in less than 13 days at 25 mg/L and 95% in 14 days at 50 mg/L). The kinetic model of Quiroga and Sales (1991) was applied to predict the biodegradation of the NPEO. The toxicity value was measured as EC(20) and EC(50). In addition, during the biodegradation process of the surfactant a toxicity analysis was made of the evolution of metabolites generated, confirming that the subproducts of the biodegradation process were more toxic than the original.

  18. Linear stability analysis of the gas injection augmented natural circulation of STAR-LM

    International Nuclear Information System (INIS)

    Yeon-Jong Yoo; Qiao Wu; James J Sienicki

    2005-01-01

    Full text of publication follows: A linear stability analysis has been performed for the gas injection augmented natural circulation of the Secure Transportable Autonomous Reactor - Liquid Metal (STAR-LM). Natural circulation is of great interest for the development of Generation-IV nuclear energy systems due to its vital role in the area of passive safety and reliability. One of such systems is STAR-LM under development by Argonne National Laboratory. STAR-LM is a 400 MWt class modular, proliferation-resistant, and passively safe liquid metal-cooled fast reactor system that uses inert lead (Pb) coolant and the advanced power conversion system that consists of a gas turbine Brayton cycle utilizing supercritical carbon dioxide (CO 2 ) to obtain higher plant efficiency. The primary loop of STAR-LM relies only on the natural circulation to eliminate the use of circulation pumps for passive safety consideration. To enhance the natural circulation of the primary coolant, STAR-LM optionally incorporates the additional driving force provided by the injection of noncondensable gas into the primary coolant above the reactor core, which is effective in removing heat from the core and transferring it to the secondary working fluid without the attainment of excessive coolant temperature at nominal operating power. Therefore, it naturally raises the concern about the natural circulation instability due to the relatively high temperature change in the core and the two-phase flow condition in the hot leg above the core. For the ease of analysis, the flow path of the loop was partitioned into five thermal-hydraulically distinct sections, i.e., heated core, unheated core, hot leg, heat exchanger, and cold leg. The one-dimensional single-phase flow field equations governing the natural circulation, i.e., continuity, momentum, and energy equations, were used for each section except the hot leg. For the hot leg, the one-dimensional homogeneous equilibrium two-phase flow field

  19. MS-Based Metabolite Profiling of Aboveground and Root Components of Zingiber mioga and Officinale.

    Science.gov (United States)

    Han, Ji Soo; Lee, Sunmin; Kim, Hyang Yeon; Lee, Choong Hwan

    2015-09-03

    Zingiber species are members of the Zingiberaceae family, and are widely used for medicinal and food purposes. In this study aboveground and root parts of Zingiber mioga and Zingiber officinale were subjected to metabolite profiling by ultra-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry (UPLC-Q-TOF-MS) and gas chromatography time-of-flight mass spectrometry (GC-TOF-MS) in order to characterize them by species and parts and also to measure bioactivities. Both primary and secondary metabolites showed clear discrimination in the PCA score plot and PLS-DA by species and parts. Tetrahydrocurcumin, diarylheptanoid, 8-gingerol, and 8-paradol were discriminating metabolites between Z. mioga and Z. officinale that were present in different quantities. Eleven flavonoids, six amino acids, six organic acids, four fatty acids, and gingerenone A were higher in the aboveground parts than the root parts. Antioxidant activities were measured and were highest in the root part of Z. officinale. The relatively high contents of tetrahydrocurcumin, diarylheptanoid, and galanganol C in the root part of Z. officinale showed highly positive correlation with bioactivities based on correlation assay. On the basis of these results, we can suggest different usages of structurally different parts of Zingiber species as food plants.

  20. Inhibition of endocannabinoid metabolism by the metabolites of ibuprofen and flurbiprofen.

    Science.gov (United States)

    Karlsson, Jessica; Fowler, Christopher J

    2014-01-01

    In addition to their effects upon prostaglandin synthesis, the non-steroidal anti-inflammatory drugs ibuprofen and flurbiprofen inhibit the metabolism of the endocannabinoids 2-arachidonoylglycerol (2-AG) and anandamide (AEA) by cyclooxygenase-2 (COX-2) and fatty acid amide hydrolase (FAAH), respectively. Here, we investigated whether these effects upon endocannabinoid metabolism are shared by the main metabolites of ibuprofen and flurbiprofen. COX activities were measured via changes in oxygen consumption due to oxygenation of arachidonic acid (for COX-1) and arachidonic acid and 2-AG (for COX-2). FAAH activity was quantified by measuring hydrolysis of tritium labelled AEA in rat brain homogenates. The ability of ibuprofen and flurbiprofen to inhibit COX-2-catalysed oxygenation of 2-AG at lower concentrations than the oxygenation of arachidonic acid was seen with 4'-hydroxyflurbiprofen and possibly also 3'-hydroxyibuprofen, albeit at lower potencies than the parent compounds. All ibuprofen and flurbiprofen metabolites retained the ability to inhibit FAAH in a pH-dependent manner, although the potency was lower than seen with the parent compounds. It is concluded that the primary metabolites of ibuprofen and flurbiprofen retain some of the properties of the parent compound with respect to inhibition of endocannabinoid metabolism. However, these effects are unlikely to contribute to the actions of the parent compounds in vivo.

  1. Inhibition of endocannabinoid metabolism by the metabolites of ibuprofen and flurbiprofen.

    Directory of Open Access Journals (Sweden)

    Jessica Karlsson

    Full Text Available In addition to their effects upon prostaglandin synthesis, the non-steroidal anti-inflammatory drugs ibuprofen and flurbiprofen inhibit the metabolism of the endocannabinoids 2-arachidonoylglycerol (2-AG and anandamide (AEA by cyclooxygenase-2 (COX-2 and fatty acid amide hydrolase (FAAH, respectively. Here, we investigated whether these effects upon endocannabinoid metabolism are shared by the main metabolites of ibuprofen and flurbiprofen.COX activities were measured via changes in oxygen consumption due to oxygenation of arachidonic acid (for COX-1 and arachidonic acid and 2-AG (for COX-2. FAAH activity was quantified by measuring hydrolysis of tritium labelled AEA in rat brain homogenates. The ability of ibuprofen and flurbiprofen to inhibit COX-2-catalysed oxygenation of 2-AG at lower concentrations than the oxygenation of arachidonic acid was seen with 4'-hydroxyflurbiprofen and possibly also 3'-hydroxyibuprofen, albeit at lower potencies than the parent compounds. All ibuprofen and flurbiprofen metabolites retained the ability to inhibit FAAH in a pH-dependent manner, although the potency was lower than seen with the parent compounds.It is concluded that the primary metabolites of ibuprofen and flurbiprofen retain some of the properties of the parent compound with respect to inhibition of endocannabinoid metabolism. However, these effects are unlikely to contribute to the actions of the parent compounds in vivo.

  2. MS-Based Metabolite Profiling of Aboveground and Root Components of Zingiber mioga and Officinale

    Directory of Open Access Journals (Sweden)

    Ji Soo Han

    2015-09-01

    Full Text Available Zingiber species are members of the Zingiberaceae family, and are widely used for medicinal and food purposes. In this study aboveground and root parts of Zingiber mioga and Zingiber officinale were subjected to metabolite profiling by ultra-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry (UPLC-Q-TOF-MS and gas chromatography time-of-flight mass spectrometry (GC-TOF-MS in order to characterize them by species and parts and also to measure bioactivities. Both primary and secondary metabolites showed clear discrimination in the PCA score plot and PLS-DA by species and parts. Tetrahydrocurcumin, diarylheptanoid, 8-gingerol, and 8-paradol were discriminating metabolites between Z. mioga and Z. officinale that were present in different quantities. Eleven flavonoids, six amino acids, six organic acids, four fatty acids, and gingerenone A were higher in the aboveground parts than the root parts. Antioxidant activities were measured and were highest in the root part of Z. officinale. The relatively high contents of tetrahydrocurcumin, diarylheptanoid, and galanganol C in the root part of Z. officinale showed highly positive correlation with bioactivities based on correlation assay. On the basis of these results, we can suggest different usages of structurally different parts of Zingiber species as food plants.

  3. [Hypertension: once primary, always primary?

    NARCIS (Netherlands)

    Braam, R.L.; Pieters, G.F.F.M.; Thien, Th.

    2002-01-01

    Three patients diagnosed with primary hypertension suddenly developed hard-to-treat blood pressure after several years of stable blood pressure. One patient, a man aged 48 years, had developed a renal artery stenosis, which had not been present five years earlier. The other two patients, a man aged

  4. Hyperthyroidism (primary)

    OpenAIRE

    Nygaard, Birte

    2010-01-01

    Hyperthyroidism is characterised by high levels of serum thyroxine and triiodothyronine, and low levels of thyroid-stimulating hormone (TSH). Thyrotoxicosis is the clinical effect of high levels of thyroid hormones, whether or not the thyroid gland is the primary source.The main causes of hyperthyroidism are Graves' disease, toxic multinodular goitre, and toxic adenoma.About 20 times more women than men have hyperthyroidism.

  5. Analytical study on thermal-hydraulic behavior of transient from forced circulation to natural circulation in JRR-3

    International Nuclear Information System (INIS)

    Hirano, Masashi; Sudo, Yukio

    1986-01-01

    Transient thermal-hydraulic behaviors of the JRR-3 which is an open-pool type research reactor has been analyzed with the THYDE-P1 code. The focal point is the thermal-hydraulic behaviors related to the core flow reversal during the transition from forced circulation downflow to natural circulation upflow. In the case of a loss-of-coolant accident (LOCA), for example, the core flow reversal is expected to occur just after the water pool isolation from the primary cooling loop with a leak. The core flow reversal should cause a sudden increase in fuel temperature and a steep decrease in the departure-from-nucleate-boiling ratio (DNBR) and the phenomenon is, therefore, very important especially for safety design and evaluation of research reactors. Major purposes of the present work are to clarify physical phenomena during the transient and to identify important parameters affecting the peak fuel temperature and the minimum DNBR. The results calculated with THYDE-P1 assuming the sequences of events of the loss-of-offsite power and LOCA help us to understand the phenomena both qualitatively and quantitatively, with respect to the safety design and evaluation. (author)

  6. Natural Circulation Capability Assessments for a Small-medium Reactor

    International Nuclear Information System (INIS)

    Choi, Sun Do

    2010-02-01

    Small-medium reactors have been highly evaluated to have more safe characteristics than those of large reactors. In addition, it could be used for a variety of purposes, such as small-scale power production in mountainous of island area, seawater desalination, regional heating system. For a higher safety, studies about a way of using natural circulation have being conducted around world. CAREM(Argentina), AST- 500(Russia), and NHR-200(china) etc. According to this tendency, REX- 10(Regional Energy rX-10) is designed in Korea for regional heating and small-scale power production. To investigate the thermal-hydraulic behavior of REX-10, we designed Rex-10 Test Facility (RTF), simulating REX-10, by using the scaling law. The scaling ratios of length, volume and power were set with 1/1, 1/50 and 1/50, respectively. The diameter and total length of RTF are 40 cm and approximately 6 m, respectively. The facility is composed of various components, which are a core in the bottom part, a heat exchanger in the middle part, a pressurizer and hot legs in the upper part, and chillers outside the facility. The test instrumentation is also designed to measure temperatures, flow rates, pressures, and pressure drop. The experiment parameters were adopted based on the 1-dimensional approach. There are a variety of parameters which influence natural circulation behavior such as heater power, overall flow resistance parameter, the distance between the center of the heat exchanger and the core. As the experimental geometries are fixed, it is found that the most important parameter is the heater power under the experimental conditions. In addition, to evaluate the effect of heater power, some experiments were conducted at varying heater power condition (from 70 kW to 170 kW) under constant primary pressure (2.0 MPa) and secondary flow rate (4.5 liter per minute). As the results of the experiments, the temperature and flow rate increase with increasing heater power. The flow rate is

  7. Steady-state metabolite concentrations reflect a balance between maximizing enzyme efficiency and minimizing total metabolite load.

    Directory of Open Access Journals (Sweden)

    Naama Tepper

    Full Text Available Steady-state metabolite concentrations in a microorganism typically span several orders of magnitude. The underlying principles governing these concentrations remain poorly understood. Here, we hypothesize that observed variation can be explained in terms of a compromise between factors that favor minimizing metabolite pool sizes (e.g. limited solvent capacity and the need to effectively utilize existing enzymes. The latter requires adequate thermodynamic driving force in metabolic reactions so that forward flux substantially exceeds reverse flux. To test this hypothesis, we developed a method, metabolic tug-of-war (mTOW, which computes steady-state metabolite concentrations in microorganisms on a genome-scale. mTOW is shown to explain up to 55% of the observed variation in measured metabolite concentrations in E. coli and C. acetobutylicum across various growth media. Our approach, based strictly on first thermodynamic principles, is the first method that successfully predicts high-throughput metabolite concentration data in bacteria across conditions.

  8. Production of Secondary Metabolites in Extreme Environments: Food- and Airborne Wallemia spp. Produce Toxic Metabolites at Hypersaline Conditions

    DEFF Research Database (Denmark)

    Jančič, Sašo; Frisvad, Jens Christian; Kocev, Dragi

    2016-01-01

    the genome data analysis of W. mellicola (previously W. sebi sensu lato) and W. ichthyophaga revealed a low number of secondary metabolites clusters, a substantial number of secondary metabolites were detected at different conditions. Machine learning analysis of the obtained dataset showed that NaCl has...... of salt or sugar. In relation to food safety, the effect of high salt and sugar concentrations on the production of secondary metabolites by this toxigenic fungus was investigated. The secondary metabolite profiles of 30 strains of the listed species were examined using general growth media, known...... to support the production of secondary metabolites, supplemented with different concentrations of NaCl, glucose and MgCl2. In more than two hundred extracts approximately one hundred different compounds were detected using high-performance liquid chromatography-diode array detection (HPLC-DAD). Although...

  9. Impact of variations of gravitational acceleration on the general circulation of the planetary atmosphere

    Science.gov (United States)

    Kilic, Cevahir; Raible, Christoph C.; Stocker, Thomas F.; Kirk, Edilbert

    2017-01-01

    Fundamental to the redistribution of energy in a planetary atmosphere is the general circulation and its meridional structure. We use a general circulation model of the atmosphere in an aquaplanet configuration with prescribed sea surface temperature and investigate the influence of the gravitational acceleration g on the structure of the circulation. For g =g0 = 9.81 ms-2 , three meridional cells exist in each hemisphere. Up to about g /g0 = 1.4 all cells increase in strength. Further increasing this ratio results in a weakening of the thermally indirect cell, such that a two- and finally a one-cell structure of the meridional circulation develops in each hemisphere. This transition is explained by the primary driver of the thermally direct Hadley cell: the diabatic heating at the equator which is proportional to g. The analysis of the energetics of the atmospheric circulation based on the Lorenz energy cycle supports this finding. For Earth-like gravitational accelerations transient eddies are primarily responsible for the meridional heat flux. For large gravitational accelerations, the direct zonal mean conversion of energy dominates the meridional heat flux.

  10. Considerations on the design of a helium circulator for a high temperature modular reactor system

    International Nuclear Information System (INIS)

    Dumm, K.; Donaldson, J.

    1988-01-01

    A modular helium cooled, high temperature reactor system with a thermal output of 200 MW per reactor has been developed by the KWU group for cogeneration of electricity and process steam. The flow of the reactor coolant - Helium at 60 bars and 250/700 deg. C is maintained by one circulator per reactor. The circulator is driven by a variable speed Siemens asynchronous motor and is submerged in the helium primary system. For operational reasons high reliability and availability of the circulator is required. The operational requirements for the circulator design are presented in this paper. The actual design has been carried out in close cooperation with the designer and manufacturer of all submerged circulators operating in AGR plants in Great Britain, James Howden Co. Renfrew, Scotland. Design solutions received so far and mainly based on sufficiently proven components - such as oil bath lubricated bearing systems - will be described. Special attention will be paid on the necessary test work; especially for the prototype to confirm the lay out. (author). 9 figs

  11. The development of natural circulation operation support program for ship nuclear power machinery

    International Nuclear Information System (INIS)

    Hao, Jianli; Chen, Wenzhen; Chen, Zhiyun

    2012-01-01

    Highlights: ► The natural circulation under various ocean and ship motion conditions is studied. ► A natural circulation operation support computer program (NCOSP) is developed with Simulink. ► The NCOSP program has the merit of easy input preparation, fast and accurate simulation. ► The NCOSP is suitable for the fast parameter simulation of ship nuclear power machinery. -- Abstract: The existing simulation program of ship nuclear power machinery (SNPM) cannot adequately deal with the natural circulation (NC) operation and the effects of various ocean conditions and ship motion. Aiming at the problem, the natural circulation operation support computer program for SNPM is developed, in which the momentum conservation equation of the primary loop, some heat transfer and flow resistance models and equations are modified for the various ocean conditions and ship motion. The additional pressure loss model and effective height model for the control volume in the gyration movement, simple harmonic rolling and pitching movements are also discussed in the paper. Furthermore, the transient response to load change under NC conditions is analyzed by the developed program. The results are compared with those predicted by the modified RELAP5/mod3.2 code. It is shown that the natural circulation operation support program (NCOSP) is simple in the input preparation, runs fast and has a satisfactory precision, and is therefore very suitable for the operating field support of SNPM under the conditions of NC.

  12. Active Upper-atmosphere Chemistry and Dynamics from Polar Circulation Reversal on Titan

    Science.gov (United States)

    Teanby, Nicholas A.; Irwin, Patrick Gerard Joseph; Nixon, Conor A.; DeKok, Remco; Vinatier, Sandrine; Coustenis, Athena; Sefton-Nash, Elliot; Calcutt, Simon B.; Flasar, Michael F.

    2012-01-01

    Saturn's moon Titan has a nitrogen atmosphere comparable to Earth's, with a surface pressure of 1.4 bar. Numerical models reproduce the tropospheric conditions very well but have trouble explaining the observed middle-atmosphere temperatures, composition and winds. The top of the middle-atmosphere circulation has been thought to lie at an altitude of 450 to 500 kilometres, where there is a layer of haze that appears to be separated from the main haze deck. This 'detached' haze was previously explained as being due to the colocation of peak haze production and the limit of dynamical transport by the circulation's upper branch. Herewe report a build-up of trace gases over the south pole approximately two years after observing the 2009 post-equinox circulation reversal, from which we conclude that middle-atmosphere circulation must extend to an altitude of at least 600 kilometres. The primary drivers of this circulation are summer-hemisphere heating of haze by absorption of solar radiation and winter-hemisphere cooling due to infrared emission by haze and trace gases; our results therefore imply that these effects are important well into the thermosphere (altitudes higher than 500 kilometres). This requires both active upper-atmosphere chemistry, consistent with the detection of high-complexity molecules and ions at altitudes greater than 950 kilometres, and an alternative explanation for the detached haze, such as a transition in haze particle growth from monomers to fractal structures.

  13. Bed system performance in helium circulation mode

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Yean Jin; Jung, Kwang Jin; Ahn, Do Hee; Chung, Hong Suk [UST, Daejeon (Korea, Republic of); Kang, Hee Suk [KAERI, Daejeon (Korea, Republic of); Yun, Sei Hun [NFRI, Deajeon (Korea, Republic of)

    2016-05-15

    As a part of the International Thermonuclear Experimental Reactor (ITER) Project, We have conducted an experiment for storing hydrogen to depleted uranium and zirconium cobalt. The helium blanket effect has been observed in experiments using metal hydrides. The collapse of the hydrogen isotopes are accompanied by the decay heat and helium-3. Helium-3 dramatically reduces the hydrogen isotope storage capacity by surrounding the metal. This phenomenon is called a helium blanket effect. In addition the authors are working on the recovery and removal techniques of helium-3. In this paper, we discuss the equipment used to test the helium blanket effect and the results of a helium circulation experiment. The helium-3 produced surrounds the storage material surface and thus disturbs the reaction of the storage material and the hydrogen isotope. Even if the amount of helium-3 is small, the storage capacity of the SDS bed significantly drops. This phenomenon is the helium blanket effect. To resolve this phenomenon, a circulating loop was introduced. Using a circulating system, helium can be separated from the storage material. We made a helium loop that includes a ZrCo bed. Then using a metal bellows pump, we tested the helium circulation.

  14. Natural circulation under severe accident conditions

    International Nuclear Information System (INIS)

    Pafford, D.J.; Hanson, D.J.; Tung, V.X.; Chmielewski, S.V.

    1992-01-01

    Research is being conducted to better understand natural circulation phenomena in mixtures of steam and noncondensibles and its influence on the temperature of the vessel internals and the hot leg, pressurizer surge line, and steam generator tubes. The temperature of these structures is important because their failure prior to reactor vessel lower head failure could reduce the likelihood of containment failure as a result of direct containment heating. Computer code calculations (MELPROG, SCDAP/RELAP5/MOD3) predict high fluid temperatures in the upper plenum resulting from in-vessel natural circulation. Using a simple model for the guide tube phenomena, high upper plenum temperatures are shown to be consistent with the relatively low temperatures that were deduced metallurgically from leadscrews removed from the TMI-2 upper plenum. Evaluation of the capabilities of the RELAP5/MOD3 computer code to predict natural circulation behavior was also performed. The code was used to model the Westinghouse natural circulation experimental facility. Comparisons between code calculations and results from experiments show good agreement

  15. Detecting Holocene changes in thermohaline circulation

    OpenAIRE

    Keigwin, L. D.; Boyle, E. A.

    2000-01-01

    Throughout the last glacial cycle, reorganizations of deep ocean water masses were coincident with rapid millennial-scale changes in climate. Climate changes have been less severe during the present interglacial, but evidence for concurrent deep ocean circulation change is ambiguous.

  16. Opportunities in CARICOM Migration : Brain Circulation, Diasporic ...

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

    Opportunities in CARICOM Migration : Brain Circulation, Diasporic Tourism, and Investment. Between 1965 and 2000, about 12% of the Caribbean labour force moved to Canada and other developed countries, making the Caribbean the largest per capita source of emigrants in the world. Remittances from these emigrants ...

  17. Oceanic Circulation. A Programmed Unit of Instruction.

    Science.gov (United States)

    Marine Maritime Academy, Castine.

    This booklet contains a programmed lesson on oceanic circulation. It is designed to allow students to progress through the subject at their own speed. Since it is written in linear format, it is suggested that students proceed through the program from "frame" to succeeding "frame." Instructions for students on how to use the booklet are included.…

  18. 3D Visualization of Global Ocean Circulation

    Science.gov (United States)

    Nelson, V. G.; Sharma, R.; Zhang, E.; Schmittner, A.; Jenny, B.

    2015-12-01

    Advanced 3D visualization techniques are seldom used to explore the dynamic behavior of ocean circulation. Streamlines are an effective method for visualization of flow, and they can be designed to clearly show the dynamic behavior of a fluidic system. We employ vector field editing and extraction software to examine the topology of velocity vector fields generated by a 3D global circulation model coupled to a one-layer atmosphere model simulating preindustrial and last glacial maximum (LGM) conditions. This results in a streamline-based visualization along multiple density isosurfaces on which we visualize points of vertical exchange and the distribution of properties such as temperature and biogeochemical tracers. Previous work involving this model examined the change in the energetics driving overturning circulation and mixing between simulations of LGM and preindustrial conditions. This visualization elucidates the relationship between locations of vertical exchange and mixing, as well as demonstrates the effects of circulation and mixing on the distribution of tracers such as carbon isotopes.

  19. Efficient Circulation of Railway Rolling Stock

    NARCIS (Netherlands)

    Alfieri, A.; Groot, R.; Kroon, L.G.; Schrijver, A.

    2006-01-01

    Railway rolling stock (locomotives, carriages, and train units) is one of the most significant cost sources for operatorsof passenger trains, both public and private. Rolling stock costsare due to material acquisition, power supply, and material maintenance. The efficient circulation of rolling

  20. Efficient Circulation of Railway Rolling Stock

    NARCIS (Netherlands)

    A. Alfieri (Arianna); R. Groot (Rutger); L.G. Kroon (Leo); A. Schrijver (Lex)

    2002-01-01

    textabstractRailway rolling stock (locomotives, carriages, and train units) is one of the most significant cost sources for operatorsof passenger trains, both public and private. Rolling stock costsare due to material acquisition, power supply, and material maintenance. The efficient circulation of

  1. Urinary Phthalate Metabolites Are Associated with Body Mass Index and Waist Circumference in Chinese School Children

    Science.gov (United States)

    Wang, Hexing; Zhou, Ying; Tang, Chuanxi; He, Yanhong; Wu, Jingui; Chen, Yue; Jiang, Qingwu

    2013-01-01

    Background Lab studies have suggested that ubiquitous phthalate exposures are related to obesity, but relevant epidemiological studies are scarce, especially for children. Objective To investigate the association of phthalate exposures with body mass index (BMI) and waist circumference (WC) in Chinese school children. Methods A cross-sectional study was conducted in three primary and three middle schools randomly selected from Changning District of Shanghai City of China in 2011–2012. According to the physical examination data in October, 2011, 124 normal weight, 53 overweight, and 82 obese students 8–15 years of age were randomly chosen from these schools on the basis of BMI-based age- and sex-specific criterion. First morning urine was collected in January, 2012, and fourteen urine phthalate metabolites (free plus conjugated) were determined by ultra-performance liquid chromatography coupled to tandem mass spectrometry. Multiple linear regression was used to explore the associations between naturally log-transformed urine phthalate metabolites and BMI or WC. Results The urine specific gravity-corrected concentrations of nine urine phthalate metabolites and five molar sums were positively associated with BMI or WC in Chinese school children after adjustment for age and sex. However, when other urine phthalate metabolites were included in the models together with age and sex as covariables, most of these significant associations disappeared except for mono (2-ethylhexyl) phthalate (MEHP) and monoethyl phthalate (MEP). Additionally, some associations showed sex- or age-specific differences. Conclusions Some phthalate exposures were associated with BMI or WC in Chinese school children. Given the cross-sectional nature of this study and lack of some important obesity-related covariables, further studies are needed to confirm the associations. PMID:23437242

  2. Metabolite profiling of bendamustine in urine of cancer patients after administration of [14C]bendamustine.

    Science.gov (United States)

    Dubbelman, Anne-Charlotte; Jansen, Robert S; Rosing, Hilde; Darwish, Mona; Hellriegel, Edward; Robertson, Philmore; Schellens, Jan H M; Beijnen, Jos H

    2012-07-01

    Bendamustine is an alkylating agent consisting of a mechlorethamine derivative, a benzimidazole group, and a butyric acid substituent. A human mass balance study showed that bendamustine is extensively metabolized and subsequently excreted in urine. However, limited information is available on the metabolite profile of bendamustine in human urine. The objective of this study was to elucidate the metabolic pathways of bendamustine in humans by identification of its metabolites excreted in urine. Human urine samples were collected up to 168 h after an intravenous infusion of 120 mg/m(2) (80-95 μCi) [(14)C]bendamustine. Metabolites of [(14)C]bendamustine were identified using liquid chromatography (high-resolution)-tandem mass spectrometry with off-line radioactivity detection. Bendamustine and a total of 25 bendamustine-related compounds were detected. Observed metabolic conversions at the benzimidazole and butyric acid moiety were N-demethylation and γ-hydroxylation. In addition, various other combinations of these conversions with modifications at the mechlorethamine moiety were observed, including hydrolysis (the primary metabolic pathway), cysteine conjugation, and subsequent biotransformation to mercapturic acid and thiol derivatives, N-dealkylation, oxidation, and conjugation with phosphate, creatinine, and uric acid. Bendamustine-derived products containing phosphate, creatinine, and uric acid conjugates were also detected in control urine incubated with bendamustine. Metabolites that were excreted up to 168 h after the infusion included products of dihydrolysis and cysteine conjugation of bendamustine and γ-hydroxybendamustine. The range of metabolic reactions is generally consistent with those reported for rat urine and bile, suggesting that the overall processes involved in metabolic elimination are qualitatively the same in rats and humans.

  3. Inhibitory effect of benzene metabolites on nuclear DNA synthesis in bone marrow cells

    International Nuclear Information System (INIS)

    Lee, E.W.; Johnson, J.T.; Garner, C.D.

    1989-01-01

    Effects of endogenously produced and exogenously added benzene metabolites on the nuclear DNA synthetic activity were investigated using a culture system of mouse bone marrow cells. Effects of the metabolites were evaluated by a 30-min incorporation of [ 3 H]thymidine into DNA following a 30-min interaction with the cells in McCoy's 5a medium with 10% fetal calf serum. Phenol and muconic acid did not inhibit nuclear DNA synthesis. However, catechol, 1,2,4-benzenetriol, hydroquinone, and p-benzoquinone were able to inhibit 52, 64, 79, and 98% of the nuclear DNA synthetic activity, respectively, at 24 μM. In a cell-free DNA synthetic system, catechol and hydroquinone did not inhibit the incorporation of [ 3 H]thymidine triphosphate into DNA up to 24 μM but 1,2,4-benzenetriol and p-benzoquinone did. The effect of the latter two benzene metabolites was completely blocked in the presence of 1,4-dithiothreitol (1 mM) in the cell-free assay system. Furthermore, when DNA polymerase α, which requires a sulfhydryl (SH) group as an active site, was replaced by DNA polymerase 1, which does not require an SH group for its catalytic activity, p-benzoquinone and 1,2,4-benzenetriol were unable to inhibit DNA synthesis. Thus, the data imply the p-benzoquinone and 1,2,4-benzenetriol inhibited DNA polymerase α, consequently resulting in inhibition of DNA synthesis in both cellular and cell-free DNA synthetic systems. The present study identifies catechol, hydroquinone, p-benzoquinone, and 1,2,4-benzenetriol as toxic benzene metabolites in bone marrow cells and also suggests that their inhibitory action on DNA synthesis is mediated by mechanism(s) other than that involving DNA damage as a primary cause

  4. Decontamination of primary cooling system

    International Nuclear Information System (INIS)

    Morikawa, Yoshitake.

    1985-01-01

    Purpose: To effectively eliminate radioactivity accumulated in pipeways, equipments, etc in primary coolant circuits of BWR type power plants by utilizing ion displacement reactions. Method: The reactor pressure vessel is connected with a feedwater pipeway, steam pipeway and a recycling pipeway. The recycling pipeway is disposed with a recycling pump. A recycling by-pass line is branched from the recycling pipeway and disposed with a recycling system heat exchanger and chemical injection point. Water is filled in the primary coolant and heated 280 0 C. Then, while maintaining water at that temperature, non-radioactive cobalt ions are injected and circulated within the system, by which radioactivity accumulated in pipeways, equipments or the likes can effectively be removed. (Horiuchi, T.)

  5. A comparison of the RELAP5/MOD3 code with the IIST natural circulation experiments

    International Nuclear Information System (INIS)

    Ferng, Y.M.; Lee, C.H.

    1995-01-01

    A series of experiments dealing with variable secondary-side cooling conditions have been conducted at the IIST facility, including the natural circulation experiments under the secondary-side conditions of normal feedwater, loss of feedwater, and full of air. Different cooling conditions at the secondary side directly affect the primary-to-secondary heat transfer and then may influence the heat removal capability of natural circulation in the primary system. The corresponding analytical work is performed using the RELAP5/MOD3 code. Good agreement is reached both qualitatively and quantitatively between the experimental data and calculated results, demonstrating the satisfactory assessment of RELAP5/MOD3 code compared with the IIST natural circulation experiments. The cooling conditions at the secondary side have no significant effect on the heat removal capability of natural circulation as long as sufficient coolant exists on the steam generator secondary side, based on current IIST data and analytical results. Continuous increase of the core temperature and system pressure is also demonstrated experimentally and analytically in the test with the secondary side dry for the sake of deficient heat transfer capability at the steam generator secondary system

  6. Observations of the summer Red Sea circulation

    Science.gov (United States)

    Sofianos, Sarantis S.; Johns, William E.

    2007-06-01

    Aiming at exploring and understanding the summer circulation in the Red Sea, a cruise was conducted in the basin during the summer of 2001 involving hydrographic, meteorological, and direct current observations. The most prominent feature, characteristic of the summer circulation and exchange with the Indian Ocean, is a temperature, salinity, and oxygen minimum located around a depth of 75 m at the southern end of the basin, associated with Gulf of Aden Intermediate Water inflowing from the Gulf of Aden during the summer season as an intruding subsurface layer. Stirring and mixing with ambient waters lead to marked increases in temperature (from 16.5 to almost 33°C) and salinity (from 35.7 to more than 38 psu) in this layer by the time it reaches midbasin. The observed circulation presents a very vigorous pattern with strong variability and intense features that extend the width of the basin. A permanent cyclone, detected in the northern Red Sea, verifies previous observations and modeling studies, while in the central sector of the basin a series of very strong anticyclones were observed with maximum velocities exceeding 1 m/s. The three-layer flow pattern, representative of the summer exchange between the Red Sea and the Gulf of Aden, is observed in the strait of Bab el Mandeb. In the southern part of the basin the layer flow is characterized by strong banking of the inflows and outflows against the coasts. Both surface and intermediate water masses involved in the summer Red Sea circulation present prominent spatial variability in their characteristics, indicating that the eddy field and mixing processes play an important role in the summer Red Sea circulation.

  7. Decontamination of CAGR gas circulator components

    International Nuclear Information System (INIS)

    Rogers, L.N.; Hooper, A.J.

    1985-01-01

    This paper describes the development and full-scale trial of two methods for removal of radioactive contamination on the surfaces of CAGR gas circulator components. The two methods described are a particle impact cleaning (PIC) decontamination technique and an electrochemical technique, 'electro-swabbing', which is based on the principle of decontamination by electro-polishing. In developing these techniques it was necessary to take account of the physical and chemical nature of the surface deposits on the gas circulator components; these were shown to consist of magnetite-type oxide and carbonaceous material. In order to follow the progress of the decontamination it was also necessary to develop a surface sampling technique which was effective and precise under these conditions; an electrochemical technique, employing similar principles to the electro-swabbing process, was developed for this purpose. The full-scale trial of the PIC decontamination technique was carried out on an inlet guide vane (IGV) assembly, this having been identified as the component from the gas circulator which contributes most to the radiation dose accumulated during routine circulator maintenance. The technique was shown to be practically viable and some 99% of the radioactive contamination was readily removed from the treated surfaces with only negligible surface damage being caused. The full-scale trial of the electro-swabbing decontamination technique was carried out on a gas circulator impeller. High decontamination factors were again achieved with ≥ 99% of the radioactive contamination being removed from the treated surfaces. The technique has practical limitations in terms of handling and treatment of waste-arisings. However, the use of specially-designed swabbing electrodes may allow the treatment of constricted geometries inaccessible to techniques such as PIC. The technique is also highly suitable for the treatment of soft-finish materials and of components fabricated from a

  8. Secondary Metabolites from Higher Fungi: Discovery, Bioactivity, and Bioproduction

    Science.gov (United States)

    Zhong, Jian-Jiang; Xiao, Jian-Hui

    Medicinal higher fungi such as Cordyceps sinensis and Ganoderma lucidum have been used as an alternative medicine remedy to promote health and longevity for people in China and other regions of the world since ancient times. Nowadays there is an increasing public interest in the secondary metabolites of those higher fungi for discovering new drugs or lead compounds. Current research in drug discovery from medicinal higher fungi involves a multifaceted approach combining mycological, biochemical, pharmacological, metabolic, biosynthetic and molecular techniques. In recent years, many new secondary metabolites from higher fungi have been isolated and are more likely to provide lead compounds for new drug discovery, which may include chemopreventive agents possessing the bioactivity of immunomodulatory, anticancer, etc. However, numerous challenges of secondary metabolites from higher fungi are encountered including bioseparation, identification, biosynthetic metabolism, and screening model issues, etc. Commercial production of secondary metabolites from medicinal mushrooms is still limited mainly due to less information about secondary metabolism and its regulation. Strategies for enhancing secondary metabolite production by medicinal mushroom fermentation include two-stage cultivation combining liquid fermentation and static culture, two-stage dissolved oxygen control, etc. Purification of bioactive secondary metabolites, such as ganoderic acids from G. lucidum, is also very important to pharmacological study and future pharmaceutical application. This review outlines typical examples of the discovery, bioactivity, and bioproduction of secondary metabolites of higher fungi origin.

  9. Metabolomics and Cheminformatics Analysis of Antifungal Function of Plant Metabolites.

    Science.gov (United States)

    Cuperlovic-Culf, Miroslava; Rajagopalan, NandhaKishore; Tulpan, Dan; Loewen, Michele C

    2016-09-30

    Fusarium head blight (FHB), primarily caused by Fusarium graminearum , is a devastating disease of wheat. Partial resistance to FHB of several wheat cultivars includes specific metabolic responses to inoculation. Previously published studies have determined major metabolic changes induced by pathogens in resistant and susceptible plants. Functionality of the majority of these metabolites in resistance remains unknown. In this work we have made a compilation of all metabolites determined as selectively accumulated following FHB inoculation in resistant plants. Characteristics, as well as possible functions and targets of these metabolites, are investigated using cheminformatics approaches with focus on the likelihood of these metabolites acting as drug-like molecules against fungal pathogens. Results of computational analyses of binding properties of several representative metabolites to homology models of fungal proteins are presented. Theoretical analysis highlights the possibility for strong inhibitory activity of several metabolites against some major proteins in Fusarium graminearum , such as carbonic anhydrases and cytochrome P450s. Activity of several of these compounds has been experimentally confirmed in fungal growth inhibition assays. Analysis of anti-fungal properties of plant metabolites can lead to the development of more resistant wheat varieties while showing novel application of cheminformatics approaches in the analysis of plant/pathogen interactions.

  10. Metabolite Profiling of Candidatus Liberibacter Infection in Hamlin Sweet Oranges.

    Science.gov (United States)

    Hung, Wei-Lun; Wang, Yu

    2018-04-18

    Huanglongbing (HLB), also known as citrus greening disease, caused by Candidatus Liberibacter asiaticus (CLas), is considered the most serious citrus disease in the world. CLas infection has been shown to greatly affect metabolite profiles in citrus fruits. However, because of uneven distribution of CLas throughout the tree and a minimum bacterial titer requirement for polymerase chain reaction (PCR) detection, the infected trees may test false negative. To prevent this, metabolites of healthy Hamlin oranges (CLas-) obtained from the citrus undercover protection systems (CUPS) were investigated. Comparison of the metabolite profile of juice obtained from CLas- and CLas+ (asymptomatic and symptomatic) trees revealed significant differences in both volatile and nonvolatile metabolites. However, no consistent pattern could be observed in alcohols, esters, sesquiterpenes, sugars, flavanones, and limonoids as compared to previous studies. These results suggest that CLas may affect metabolite profiles of citrus fruits earlier than detecting infection by PCR. Citric acid, nobiletin, malic acid, and phenylalanine were identified as the metabolic biomarkers associated with the progression of HLB. Thus, the differential metabolites found in this study may serve as the biomarkers of HLB in its early stage, and the metabolite signature of CLas infection may provide useful information for developing a potential treatment strategy.

  11. Direct detection of glucuronide metabolites of lidocaine in sheep urine.

    Science.gov (United States)

    Doran, Gregory S; Smith, Alistair K; Rothwell, Jim T; Edwards, Scott H

    2018-02-15

    The anaesthetic lidocaine is metabolised quickly to produce a series of metabolites, including several hydroxylated metabolites, which are further metabolised by addition of a glucuronic acid moiety. Analysis of these glucuronide metabolites in urine is performed indirectly by cleaving the glucuronic acid group using β-glucuronidase. However, direct analysis of intact glucuronide conjugates is a more straightforward approach as it negates the need for long hydrolysis incubations, and minimises the oxidation of sensitive hydrolysis products, while also distinguishing between the two forms of hydroxylated metabolites. A method was developed to identify three intact glucuronides of lidocaine in sheep urine using LC-MS/MS, which was further confirmed by the synthesis of glucuronide derivatives of 3OH-MEGX and 4OH-LIDO. Direct analysis of urine allowed the detection of the glucuronide metabolites of hydroxylidocaine (OH-LIDO), hydroxyl-monoethylglycinexylidide (OH-MEGX), and hydroxy-2,6-xylidine (OH-XYL). Analysis of urine before and after β-glucuronidase digestion showed that the efficiency of hydrolysis of these glucuronide metabolites may be underestimated in some studies. Analysis of urine in the current study from three different sheep with similar glucuronide metabolite concentrations resulted in different hydrolysis efficiencies, which may have been a result of different levels of substrate binding by matrix components, preventing enzyme cleavage. The use of direct analysis of intact glucuronides has the benefit of being less influenced by these matrix effects, while also allowing analysis of unstable metabolites like 4OH-XYL, which rapidly oxidises after hydrolysis. Additionally, direct analysis is less expensive and less time consuming, while providing more information about the status of hydroxylated metabolites in urine. Crown Copyright © 2018. Published by Elsevier B.V. All rights reserved.

  12. Probiotic metabolites from Bacillus coagulans GanedenBC30TM support maturation of antigen-presenting cells in vitro

    Science.gov (United States)

    Benson, Kathleen F; Redman, Kimberlee A; Carter, Steve G; Keller, David; Farmer, Sean; Endres, John R; Jensen, Gitte S

    2012-01-01

    AIM: To study the effects of probiotic metabolites on maturation stage of antigen-presenting immune cells. METHODS: Ganeden Bacillus coagulans 30 (GBC30) bacterial cultures in log phase were used to isolate the secreted metabolite (MET) fraction. A second fraction was made to generate a crude cell-wall-enriched fraction, by centrifugation and lysis, followed by washing. A preparation of MET was subjected to size exclusion centrifugation, generating three fractions: < 3 kDa, 3-30 kDa, and 30-200 kDa and activities were tested in comparison to crude MET and cell wall in primary cultures of human peripheral blood mononuclear cell (PBMC) as a source of antigen-presenting mononuclear phagocytes. The maturation status of mononuclear phagocytes was evaluated by staining with monoclonal antibodies towards CD14, CD16, CD80 and CD86 and analyzed by flow cytometry. RESULTS: Treatment of PBMC with MET supported maturation of mononuclear phagocytes toward both macrophage and dendritic cell phenotypes. The biological activity unique to the metabolites included a reduction of CD14+ CD16+ pro-inflammatory cells, and this property was associated with the high molecular weight metabolite fraction. Changes were also seen for the dendritic cell maturation markers CD80 and CD86. On CD14dim cells, an increase in both CD80 and CD86 expression was seen, in contrast to a selective increase in CD86 expression on CD14bright cells. The co-expression of CD80 and CD86 indicates effective antigen presentation to T cells and support of T helper cell differentiation. The selective expression of CD86 in the absence of CD80 points to a role in generating T regulatory cells. CONCLUSION: The data show that a primary mechanism of action of GBC30 metabolites involves support of more mature phenotypes of antigen-presenting cells, important for immunological decision-making. PMID:22563167

  13. Natural occurrence of fungi and fungal metabolites in moldy tomatoes

    DEFF Research Database (Denmark)

    Andersen, B.; Frisvad, Jens Christian

    2004-01-01

    Fresh tomatoes, homegrown and from supermarkets, with developing fungal lesions were collected. Each lesion was sampled, and the resulting fungal cultures were identified morphologically, and extracted for analyzes of secondary metabolites. The tomatoes were incubated at 25 degreesC for a week....... extracted, and analyzed for fungal metabolites. Extracts from pure cultures were compared with extracts from the moldy tomatoes and fungal metabolite standards in two HPLC systems with DAD and FLD detection. The results showed that Penicillium tularense, Stemphylium eturmiunum. and S. cf. lycopersici were...

  14. In Vitro Analysis of Metabolite Transport Proteins.

    Science.gov (United States)

    Roell, Marc-Sven; Kuhnert, Franziska; Zamani-Nour, Shirin; Weber, Andreas P M

    2017-01-01

    The photorespiratory cycle is distributed over four cellular compartments, the chloroplast, peroxisomes, cytoplasm, and mitochondria. Shuttling of photorespiratory intermediates between these compartments is essential to maintain the function of photorespiration. Specific transport proteins mediate the transport across biological membranes and represent important components of the cellular metabolism. Although significant progress was made in the last years on identifying and characterizing new transport proteins, the overall picture of intracellular metabolite transporters is still rather incomplete. The photorespiratory cycle requires at least 25 transmembrane transport steps; however to date only plastidic glycolate/glycerate transporter and the accessory 2-oxoglutarate/malate and glutamate/malate transporters as well as the mitochondrial transporter BOU1 have been identified. The characterization of transport proteins and defining their substrates and kinetics are still major challenges.Here we present a detailed set of protocols for the in vitro characterization of transport proteins. We provide protocols for the isolation of recombinant transport protein expressed in E. coli or Saccharomyces cerevisiae and the extraction of total leaf membrane protein for in vitro analysis of transporter proteins. Further we explain the process of reconstituting transport proteins in artificial lipid vesicles and elucidate the details of transport assays.

  15. Dietary Metabolites and Chronic Kidney Disease

    Directory of Open Access Journals (Sweden)

    Sho Hasegawa

    2017-04-01

    Full Text Available Dietary contents and their metabolites are closely related to chronic kidney disease (CKD progression. Advanced glycated end products (AGEs are a type of uremic toxin produced by glycation. AGE accumulation is not only the result of elevated glucose levels or reduced renal clearance capacity, but it also promotes CKD progression. Indoxyl sulfate, another uremic toxin derived from amino acid metabolism, accumulates as CKD progresses and induces tubulointerstitial fibrosis and glomerular sclerosis. Specific types of amino acids (d-serine or fatty acids (palmitate are reported to be closely associated with CKD progression. Promising therapeutic targets associated with nutrition include uremic toxin absorbents and inhibitors of AGEs or the receptor for AGEs (RAGE. Probiotics and prebiotics maintain gut flora balance and also prevent CKD progression by enhancing gut barriers and reducing uremic toxin formation. Nrf2 signaling not only ameliorates oxidative stress but also reduces elevated AGE levels. Bardoxolone methyl, an Nrf2 activator and NF-κB suppressor, has been tested as a therapeutic agent, but the phase 3 clinical trial was terminated owing to the high rate of cardiovascular events. However, a phase 2 trial has been initiated in Japan, and the preliminary analysis reveals promising results without an increase in cardiovascular events.

  16. Experimental investigation on natural circulation and air-injection enhanced circulation in a simple loop

    International Nuclear Information System (INIS)

    Walter Ambrosini; Nicola Forgione; Francesco Oriolo; Filippo Pellacani; Mariano Tarantino; Claudio Struckmann

    2005-01-01

    Full text of publication follows: Natural circulation represents an interesting phenomenon because of both the complex aspects characterising it and for the widespread application in industry. On the other hand, injection of a gas into a rising branch of a loop represents a means to establish or to enhance a circulation flow, as it occurs in the so-called 'air-lift' loops. Both natural circulation and gas-injection enhanced circulation are presently considered for cooling Accelerator Driven System (ADS) reactors. These are subcritical reactors in which the fission reaction chain is maintained by the injection of neutrons obtained by spallation reactions in a target through a high energy proton beam generated in an external accelerator. The capability of such reactors to be used as incinerators of long lived fission products makes them particularly interesting in the light of the closure of the nuclear fuel cycle. Some of the fluids proposed as coolants for these reactors are liquid metals, with main interest for lead and lead-bismuth eutectic (LBE). Experimental activities are being performed in support to the design of the reactor prototype by different organisations. The university of Pisa, in addition to provide cooperation in these large scale activities performed with LBE has set up a specific experimental program aimed at studying the fundamental mechanisms involved in natural circulation and gas-injection enhanced circulation. The adopted experimental facility consists in a simple loop, having a rectangular lay-out (roughly, 4 m tall and 1 m wide), equipped with a 5 kW, 1 m tall heater, a 2 m long pipe-in-pipe heat exchanger, an air injection device and a separator. The fluid adopted in the tests performed up to now is water, though studies for evaluating the feasibility of the adoption of different fluids have been undertaken. Experimental data reported in previous publications concerning this research were related to a relatively high range of gas

  17. Money circulation and debt circulation: A restatement of quantity theory of money

    OpenAIRE

    Xing, Xiaoyun; Xiong, Wanting; Chen, Liujun; Chen, Jiawei; Wang, Yougui; Stanley, H. Eugene

    2018-01-01

    Both money and debt are products of credit creation of banks. Money is always circulating among traders by facilitating commodity transactions. In contrast, debt is created by borrowing and annihilated by repayment as it is matured. However, when this creation- annihilation process is mediated by banks which are constrained by a credit capacity, there exists continuous transfer of debt among debtors, which can be defined as debt circulation. This paper presents a multi-agent model in which in...

  18. Development and verification of a space-dependent dynamic model of a natural circulation steam generator

    International Nuclear Information System (INIS)

    Mewdell, C.G.; Harrison, W.C.; Hawley, E.H.

    1980-01-01

    This paper describes the development and verification of a Non-Linear Space-Dependent Dynamic Model of a Natural Circulation Steam Generator typical of boilers used in CANDU nuclear power stations. The model contains a detailed one-dimensional dynamic description of both the primary and secondary sides of an integral pre-heater natural circulation boiler. Two-phase flow effects on the primary side are included. The secondary side uses a drift-flux model in the boiling sections and a detailed non-equilibrium point model for the steam drum. The paper presents the essential features of the final model called BOILER-2, its solution scheme, the RD-12 loop and test boiler, the boiler steady-state and transient experiments, and the comparison of the model predictions with experimental results. (author)

  19. Prioritizing Candidate Disease Metabolites Based on Global Functional Relationships between Metabolites in the Context of Metabolic Pathways

    Science.gov (United States)

    Yang, Haixiu; Xu, Yanjun; Han, Junwei; Li, Jing; Su, Fei; Zhang, Yunpeng; Zhang, Chunlong; Li, Dongguo; Li, Xia

    2014-01-01

    Identification of key metabolites for complex diseases is a challenging task in today's medicine and biology. A special disease is usually caused by the alteration of a series of functional related metabolites having a global influence on the metabolic network. Moreover, the metabolites in the same metabolic pathway are often associated with the same or similar disease. Based on these functional relationships between metabolites in the context of metabolic pathways, we here presented a pathway-based random walk method called PROFANCY for prioritization of candidate disease metabolites. Our strategy not only takes advantage of the global functional relationships between metabolites but also sufficiently exploits the functionally modular nature of metabolic networks. Our approach proved successful in prioritizing known metabolites for 71 diseases with an AUC value of 0.895. We also assessed the performance of PROFANCY on 16 disease classes and found that 4 classes achieved an AUC value over 0.95. To investigate the robustness of the PROFANCY, we repeated all the analyses in two metabolic networks and obtained similar results. Then we applied our approach to Alzheimer's disease (AD) and found that a top ranked candidate was potentially related to AD but had not been reported previously. Furthermore, our method was applicable to prioritize the metabolites from metabolomic profiles of prostate cancer. The PROFANCY could identify prostate cancer related-metabolites that are supported by literatures but not considered to be significantly differential by traditional differential analysis. We also developed a freely accessible web-based and R-based tool at http://bioinfo.hrbmu.edu.cn/PROFANCY. PMID:25153931

  20. Circulating and plateout activity program for gas-cooled reactors with arbitrary radioactive chains

    International Nuclear Information System (INIS)

    Apperson, C.E. Jr.

    1978-03-01

    A time-dependent method for estimating the fuel body, circulating, plateout, and filter inventory of a high temperature gas-cooled reactor (HTGR) during normal operation is discussed. The primary coolant model accounts for the source, buildup, decay, and cleanup of isotopes that are gas borne inside the prestressed concrete reactor vessel (PCRV). This method has been implemented in the SUVIUS computer program that is described in detail

  1. Prediction of Drug-Drug Interactions with Bupropion and Its Metabolites as CYP2D6 Inhibitors Using a Physiologically-Based Pharmacokinetic Model.

    Science.gov (United States)

    Xue, Caifu; Zhang, Xunjie; Cai, Weimin

    2017-12-21

    The potential of inhibitory metabolites of perpetrator drugs to contribute to drug-drug interactions (DDIs) is uncommon and underestimated. However, the occurrence of unexpected DDI suggests the potential contribution of metabolites to the observed DDI. The aim of this study was to develop a physiologically-based pharmacokinetic (PBPK) model for bupropion and its three primary metabolites-hydroxybupropion, threohydrobupropion and erythrohydrobupropion-based on a mixed "bottom-up" and "top-down" approach and to contribute to the understanding of the involvement and impact of inhibitory metabolites for DDIs observed in the clinic. PK profiles from clinical researches of different dosages were used to verify the bupropion model. Reasonable PK profiles of bupropion and its metabolites were captured in the PBPK model. Confidence in the DDI prediction involving bupropion and co-administered CYP2D6 substrates could be maximized. The predicted maximum concentration (C max ) area under the concentration-time curve (AUC) values and C max and AUC ratios were consistent with clinically observed data. The addition of the inhibitory metabolites into the PBPK model resulted in a more accurate prediction of DDIs (AUC and C max ratio) than that which only considered parent drug (bupropion) P450 inhibition. The simulation suggests that bupropion and its metabolites contribute to the DDI between bupropion and CYP2D6 substrates. The inhibitory potency from strong to weak is hydroxybupropion, threohydrobupropion, erythrohydrobupropion, and bupropion, respectively. The present bupropion PBPK model can be useful for predicting inhibition from bupropion in other clinical studies. This study highlights the need for caution and dosage adjustment when combining bupropion with medications metabolized by CYP2D6. It also demonstrates the feasibility of applying the PBPK approach to predict the DDI potential of drugs undergoing complex metabolism, especially in the DDI involving inhibitory

  2. Decrease in Circulating Fatty Acids Is Associated with Islet Dysfunction in Chronically Sleep-Restricted Rats

    Directory of Open Access Journals (Sweden)

    Shanshan Zhan

    2016-12-01

    Full Text Available Previous studies have shown that sleep restriction-induced environmental stress is associated with abnormal metabolism, but the underlying mechanism is poorly understood. In the current study, we investigated the possible lipid and glucose metabolism patterns in chronically sleep-restricted rat. Without changes in food intake, body weight was decreased and energy expenditure was increased in sleep-restricted rats. The effects of chronic sleep disturbance on metabolites in serum were examined using 1H NMR metabolomics and GC-FID/MS analysis. Six metabolites (lipoproteins, triglycerides, isoleucine, valine, choline, and phosphorylcholine exhibited significant alteration, and all the fatty acid components were decreased, which suggested fatty acid metabolism was impaired after sleep loss. Moreover, increased blood glucose, reduced serum insulin, decreased glucose tolerance, and impaired glucose-stimulated insulin secretion of islets were also observed in sleep-restricted rats. The islet function of insulin secretion could be partially restored by increasing dietary fat to sleep-disturbed rats suggested that a reduction in circulating fatty acids was related to islet dysfunction under sleep deficiency-induced environmental stress. This study provides a new perspective on the relationship between insufficient sleep and lipid/glucose metabolism, which offers insights into the role of stressful challenges in a healthy lifestyle.

  3. Celecoxib use and circulating oxylipins in a colon polyp prevention trial.

    Directory of Open Access Journals (Sweden)

    Jessica A Martinez

    Full Text Available Drugs that inhibit cyclooxygenase (COX-2 and the metabolism of arachidonic acid (ARA to prostaglandin E2 are potent anti-inflammatory agents used widely in the treatment of joint and muscle pain. Despite their benefits, daily use of these drugs has been associated with hypertension, cardiovascular and gastrointestinal toxicities. It is now recognized that ARA is metabolized to a number of bioactive oxygenated lipids (oxylipins by cyclooxygenase (COX, lipoxygenase (LOX, and cytochrome P450 (CYP450 enzymes. Currently, the contribution of individual variability in ARA metabolism in response to the COX-2 inhibitors and potential adverse effects remains poorly understood. Using patient samples from the randomized, placebo-controlled phase III selenium/celecoxib (Sel/Cel trial for the prevention of colorectal adenomatous polyps, we analyzed plasma concentrations of 74 oxylipins in a subset of participants who received celecoxib (n = 90 or placebo (n = 95. We assessed the effect of celecoxib (with and without low dose aspirin on circulating oxylipins and systolic blood pressure (SBP. Individual CYP450- and LOX- but not COX-derived metabolites were higher with celecoxib than placebo (P<0.05 and differences were greater among non-aspirin users. LOX derived 5- and 8-HETE were elevated with celecoxib and positively associated with systolic blood pressure (P = 0.011 and P = 0.019 respectively. 20-HETE, a prohypertensive androgen-sensitive CYP450 metabolite was higher with celecoxib absent aspirin and was positively associated with SBP in men (P = 0.040 but not women. Independent of celecoxib or aspirin, LOX derived metabolites from ARA were strongly associated with SBP including 5- and 8-HETE. These findings support oxylipins, particularly the ARA LOX-derived, in blood pressure control and indicate that pharmacologic inhibition of COX-2 has effects on LOX and CYP450 ARA metabolism that contribute to hypertension in some patients.

  4. Modelling the Seasonal Overturning Circulation in the Red Sea

    KAUST Repository

    Yao, Fengchao; Hoteit, Ibrahim; Pratt, Larry; Bower, Amy; Koehl, Armin; Gopalakrishnan, Ganesh

    2015-01-01

    The overturning circulation in the Red Sea exhibits a distinct seasonally reversing pattern and is studied using 50-year, high-resolution MIT general circulation model simulations. The seasonal water exchange in the Strait of Bab el Mandeb

  5. Silent Circulation of Ross River Virus in French Polynesia

    Directory of Open Access Journals (Sweden)

    Maite Aubry

    2015-08-01

    Discussion: Our results support the existence of autochthonous RRV transmission and suggest that this pathogen has silently circulated in French Polynesia. These findings raise the question of possible undetected circulation of RRV in other Pacific Island Countries and Territories.

  6. Distinct proteome pathology of circulating microparticles in systemic lupus erythematosus

    DEFF Research Database (Denmark)

    Østergaard, Ole; Nielsen, Christoffer Tandrup; Tanassi, Julia T

    2017-01-01

    BACKGROUND: The pathogenesis of systemic lupus erythematosus (SLE) is poorly understood but has been linked to defective clearance of subcellular particulate material from the circulation. This study investigates the origin, formation, and specificity of circulating microparticles (MPs) in patients...

  7. Circulation induced by diffused aeration in a shallow lake

    African Journals Online (AJOL)

    2017-01-01

    Jan 1, 2017 ... Lastly, a simple returning flow model was proposed to describe the circulation flow patterns ... method to describe the circulation patterns induced by the bub- ... 160 holes of 1 mm, which was designed to promote high mix-.

  8. Uptake and degradation of circulating proteins by the liver.

    NARCIS (Netherlands)

    Buys, Carolus Henricus Cornelis Maria

    1976-01-01

    Circulating proteins, like all proteins in a living animal, are subject to continual replacement or turnover. This process implies both synthesis and degradation, This thesis deals with the degradative part of turnover of circulating proteins. ... Summary

  9. Characterization and identification of in vitro metabolites of ...

    African Journals Online (AJOL)

    trap orbitrap mass spectrometry (UHPLC-LTQ-Orbitap MS). Results: Nine metabolites of (-)-epicatechin were characterized on the basis of high resolution mass measurement, MS spectra and literature data. Based on their structures, the major ...

  10. Metabolites: messengers between the microbiota and the immune system.

    Science.gov (United States)

    Levy, Maayan; Thaiss, Christoph A; Elinav, Eran

    2016-07-15

    The mammalian intestine harbors one of the largest microbial densities on Earth, necessitating the implementation of control mechanisms by which the host evaluates the state of microbial colonization and reacts to deviations from homeostasis. While microbial recognition by the innate immune system has been firmly established as an efficient means by which the host evaluates microbial presence, recent work has uncovered a central role for bacterial metabolites in the orchestration of the host immune response. In this review, we highlight examples of how microbiota-modulated metabolites control the development, differentiation, and activity of the immune system and classify them into functional categories that illustrate the spectrum of ways by which microbial metabolites influence host physiology. A comprehensive understanding of how microbiota-derived metabolites shape the human immune system is critical for the rational design of therapies for microbiota-driven diseases. © 2016 Levy et al.; Published by Cold Spring Harbor Laboratory Press.

  11. Ruta graveolens Extracts and Metabolites against Spodoptera frugiperda.

    Science.gov (United States)

    Ayil-Gutiérrez, Benjamin A; Villegas-Mendoza, Jesús M; Santes-Hernndez, Zuridai; Paz-González, Alma D; Mireles-Martínez, Maribel; Rosas-García, Ninfa M; Rivera, Gildardo

    2015-11-01

    The biological activity of Ruta graveolens leaf tissue extracts obtained with different solvents (ethyl acetate, ethanol, and water) and metabolites (psoralen, 2- undecanone and rutin) against Spodoptera frugiperda was evaluated. Metabolites levels in extracts were quantified by HPLC and GC. Ethyl acetate and ethanol extracts showed 94% and 78% mortality, respectively. Additionally, psoralen metabolite showed a high mortality as cypermethrin. Metabolite quantification in extracts shows the presence of 2-undecanone (87.9 µmoles mg(-1) DW), psoralen (3.6 µmoles mg(-1) DW) and rutin (0.001 pmoles mg(-1) DW). We suggest that these concentrations of 2-undecanone and psoralen in R. graveolens leaf tissue extracts could be responsible for S. frugiperda mortality.

  12. Isolation and identification of two galangin metabolites from rat urine ...

    African Journals Online (AJOL)

    Isolation and identification of two galangin metabolites from rat urine and determination of their in vitro hypolipidemic activity. Xuguang Zhang, Shouqian Cheng, Hailong Li, Xiaopo Zhang, Feng Chen, Youbin Li, Junqing Zhang, Yinfeng Tan ...

  13. Metabolite Signatures of Metabolic Risk Factors and their Longitudinal Changes

    NARCIS (Netherlands)

    Yin, X.; Subramanian, S.; Willinger, C.M.; Chen, G.; Juhasz, P.; Courchesne, P.; Chen, B.H.; Li, X.; Hwang, S.J.; Fox, C.S.; O'Donnell, C.J.; Muntendam, P.; Fuster, V.; Bobeldijk-Pastorova, I.; Sookoian, S.C.; Pirola, C.J.; Gordon, N.; Adourian, A.; Larson, M.G.; Levy, D.

    2016-01-01

    Context: Metabolic dysregulation underlies key metabolic risk factors—obesity, dyslipidemia, and dysglycemia. Objective: To uncover mechanistic links between metabolomic dysregulation and metabolic risk by testing metabolite associations with risk factors cross-sectionally and with risk factor

  14. β-Orcinol Metabolites from the Lichen Hypotrachyna revoluta

    Directory of Open Access Journals (Sweden)

    Panagiota Papadopoulou

    2007-05-01

    Full Text Available Four new β-orcinol metabolites, hypotrachynic acid (1, deoxystictic acid (2, cryptostictinolide (3 and 8 ́-methylconstictic acid (4 along with the metabolites 8 ́-methylstictic acid (5, 8 ́-methylmenegazziaic acid (6, stictic acid (7, 8 ́-ethylstictic acid (8 and atranorin (9, that have been previously described, were isolated for the first time from the tissue extracts of the lichen Hypotrachyna revoluta (Flörke Hale. The structures of the new metabolites were elucidated on the basis of extensive spectroscopic analyses. Radical scavenging activity (RSA of the metabolites isolated in adequate amounts, was evaluated using luminol chemiluminescence and comparison with Trolox®.

  15. Detection of mastitis pathogens by analysis of volatile bacterial metabolites

    NARCIS (Netherlands)

    Hettinga, K.A.; Valenberg, van H.J.F.; Lam, T.J.G.M.; Hooijdonk, van A.C.M.

    2008-01-01

    The ability to detect mastitis pathogens based on their volatile metabolites was studied. Milk samples from cows with clinical mastitis, caused by Staphylococcus aureus, coagulase-negative staphylococci, Streptococcus uberis, Streptococcus dysgalactiae, and Escherichia coli were collected. In

  16. Characterization and identification of in vitro metabolites of ...

    African Journals Online (AJOL)

    Characterization and identification of in vitro metabolites of (-)-epicatechin using ultra-high performance liquid chromatography-mass spectrometry. Rui Jun Cai, Xiao Ling Yin, Jing Liu, Da Xu Qin, Gui Zhen Zhao ...

  17. Screening of diseases associated with abnormal metabolites for ...

    African Journals Online (AJOL)

    Dina A. Ghoraba

    2013-12-09

    Dec 9, 2013 ... IEMs to evaluate the efficiency of HPLC in detecting abnormal metabolites in urine samples. ... the initial screening of organic acid disorders and many other disease ..... Although a chromatogram from a patient with gross.

  18. A Review of the Secondary Metabolites and Biological Activities of ...

    African Journals Online (AJOL)

    School of Chemical Sciences, Universiti Sains Malaysia, Penang 11800, Malaysia ... ulcers. A wide range of secondary metabolites such as alkaloids, diterpenes, flavones, phenolics, and triterpenes .... potency than the synthetic antioxidant.

  19. Secondary metabolites of the argan tree (Morocco) may have ...

    African Journals Online (AJOL)

    Administrator

    knowledge, researchers are screening metabolites of this rare plant to identify bioactive compounds for .... or 29 carbon atoms. ... argan oil does not absorb oxygen to form hydroperoxides ..... dioxide: superiority to alpha-tocopherol. Proc. Nat.

  20. Extraction and applications of cyanotoxins and other cyanobacterial secondary metabolites.

    Science.gov (United States)

    Haque, Fatima; Banayan, Sara; Yee, Josephine; Chiang, Yi Wai

    2017-09-01

    The rapid proliferation of cyanobacteria in bodies of water has caused cyanobacterial blooms, which have become an increasing cause of concern, largely due to the presence of toxic secondary metabolites (or cyanotoxins). Cyanotoxins are the toxins produced by cyanobacteria that may be harmful to surrounding wildlife. They include hepatotoxins, neurotoxins and dermatotoxins, and are classified based on the organs they affect. There are also non-toxic secondary metabolites that include chelators and UV-absorbing compounds. This paper summarizes the optimal techniques for secondary metabolite extraction and the possible useful products that can be obtained from cyanobacteria, with additional focus given to products derived from secondary metabolites. It becomes evident that the potential for their use as biocides, chelators, biofuels, biofertilizers, pharmaceuticals, food and feed, and cosmetics has not yet been comprehensively studied or extensively implemented. Copyright © 2017 Elsevier Ltd. All rights reserved.