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Sample records for pipelined metabolite identification

  1. Prioritization of putative metabolite identifications in LC-MS/MS experiments using a computational pipeline.

    Science.gov (United States)

    Zhou, Bin; Xiao, Jun Feng; Ressom, Habtom W

    2013-01-01

    One of the major bottle-necks in current LC-MS-based metabolomic investigations is metabolite identification. An often-used approach is to first look up metabolites from databases through peak mass, followed by verification of the obtained putative identifications using MS/MS data. However, the mass-based search may provide inappropriate putative identifications when the observed peak is from isotopes, fragments, or adducts. In addition, a large fraction of peaks is often left with multiple putative identifications. To differentiate these putative identifications, manual verification of metabolites through comparison between biological samples and authentic compounds is necessary. However, such experiments are laborious, especially when multiple putative identifications are encountered. It is desirable to use computational approaches to obtain more reliable putative identifications and prioritize them before performing experimental verification of the metabolites. In this article, a computational pipeline is proposed to assist metabolite identification with improved metabolome coverage and prioritization capability. Multiple publicly available software tools and databases, along with in-house developed algorithms, are utilized to fully exploit the information acquired from LC-MS/MS experiments. The pipeline is successfully applied to identify metabolites on the basis of LC-MS as well as MS/MS data. Using accurate masses, retention time values, MS/MS spectra, and metabolic pathways/networks, more appropriate putative identifications are retrieved and prioritized to guide subsequent metabolite verification experiments.

  2. A Nontargeted UHPLC-HRMS Metabolomics Pipeline for Metabolite Identification: Application to Cardiac Remote Ischemic Preconditioning.

    Science.gov (United States)

    Kouassi Nzoughet, Judith; Bocca, Cinzia; Simard, Gilles; Prunier-Mirebeau, Delphine; Chao de la Barca, Juan Manuel; Bonneau, Dominique; Procaccio, Vincent; Prunier, Fabrice; Lenaers, Guy; Reynier, Pascal

    2017-02-07

    In recent years, the number of investigations based on nontargeted metabolomics has increased, although often without a thorough assessment of analytical strategies applied to acquire data. Following published guidelines for metabolomics experiments, we report a validated nontargeted metabolomics strategy with pipeline for unequivocal identification of metabolites using the MSMLS molecule library. We achieved an in-house database containing accurate m/z values, retention times, isotopic patterns, full MS, and MS/MS spectra. A UHPLC-HRMS Q-Exactive method was developed, and experimental variations were determined within and between 3 experimental days. The extraction efficiency as well as the accuracy, precision, repeatability, and linearity of the method were assessed, the method demonstrating good performances. The methodology was further blindly applied to plasma from remote ischemic pre-conditioning (RIPC) rats. Samples, previously analyzed by targeted metabolomics using completely different protocol, analytical strategy, and platform, were submitted to our analytical pipeline. A combination of multivariate and univariate statistical analyses was employed. Selection of putative biomarkers from OPLS-DA model and S-plot was combined to jack-knife confidence intervals, metabolites' VIP values, and univariate statistics. Only variables with strong model contribution and highly statistical reliability were selected as discriminated metabolites. Three biomarkers identified by the previous targeted metabolomics study were found in the current work, in addition to three novel metabolites, emphasizing the efficiency of the current methodology and its ability to identify new biomarkers of clinical interest, in a single sequence. The biomarkers were identified to level 1 according to the metabolomics standard initiative and confirmed by both RPLC and HILIC-HRMS.

  3. Protein Identification Pipeline for the Homology Driven Proteomics

    Science.gov (United States)

    Junqueira, Magno; Spirin, Victor; Balbuena, Tiago Santana; Thomas, Henrik; Adzhubei, Ivan; Sunyaev, Shamil; Shevchenko, Andrej

    2008-01-01

    Homology-driven proteomics is a major tool to characterize proteomes of organisms with unsequenced genomes. This paper addresses practical aspects of automated homology–driven protein identifications by LC-MS/MS on a hybrid LTQ Orbitrap mass spectrometer. All essential software elements supporting the presented pipeline are either hosted at the publicly accessible web server, or are available for free download. PMID:18639657

  4. Bioinformatics pipeline for functional identification and characterization of proteins

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    Skarzyńska, Agnieszka; Pawełkowicz, Magdalena; Krzywkowski, Tomasz; Świerkula, Katarzyna; PlÄ der, Wojciech; Przybecki, Zbigniew

    2015-09-01

    The new sequencing methods, called Next Generation Sequencing gives an opportunity to possess a vast amount of data in short time. This data requires structural and functional annotation. Functional identification and characterization of predicted proteins could be done by in silico approches, thanks to a numerous computational tools available nowadays. However, there is a need to confirm the results of proteins function prediction using different programs and comparing the results or confirm experimentally. Here we present a bioinformatics pipeline for structural and functional annotation of proteins.

  5. Emerging New Strategies for Successful Metabolite Identification in Metabolomics

    Energy Technology Data Exchange (ETDEWEB)

    Bingol, Ahmet K.; Bruschweiler-Li, Lei; Li, Dawei; Zhang, Bo; Xie, Mouzhe; Bruschweiler, Rafael

    2016-02-26

    NMR is a very powerful tool for the identification of known and unknown (or unnamed) metabolites in complex mixtures as encountered in metabolomics. Known compounds can be reliably identified using 2D NMR methods, such as 13C-1H HSQC, for which powerful web servers with databases are available for semi-automated analysis. For the identification of unknown compounds, new combinations of NMR with MS have been developed recently that make synergistic use of the mutual strengths of the two techniques. The use of chemical additives to the NMR tube, such as reactive agents, paramagnetic ions, or charged silica nanoparticles, permit the identification of metabolites with specific physical chemical properties. In the following sections, we give an overview of some of the recent advances in metabolite identification and discuss remaining challenges.

  6. Metabolite identification and molecular fingerprint prediction through machine learning.

    Science.gov (United States)

    Heinonen, Markus; Shen, Huibin; Zamboni, Nicola; Rousu, Juho

    2012-09-15

    Metabolite identification from tandem mass spectra is an important problem in metabolomics, underpinning subsequent metabolic modelling and network analysis. Yet, currently this task requires matching the observed spectrum against a database of reference spectra originating from similar equipment and closely matching operating parameters, a condition that is rarely satisfied in public repositories. Furthermore, the computational support for identification of molecules not present in reference databases is lacking. Recent efforts in assembling large public mass spectral databases such as MassBank have opened the door for the development of a new genre of metabolite identification methods. We introduce a novel framework for prediction of molecular characteristics and identification of metabolites from tandem mass spectra using machine learning with the support vector machine. Our approach is to first predict a large set of molecular properties of the unknown metabolite from salient tandem mass spectral signals, and in the second step to use the predicted properties for matching against large molecule databases, such as PubChem. We demonstrate that several molecular properties can be predicted to high accuracy and that they are useful in de novo metabolite identification, where the reference database does not contain any spectra of the same molecule. An Matlab/Python package of the FingerID tool is freely available on the web at http://www.sourceforge.net/p/fingerid. markus.heinonen@cs.helsinki.fi.

  7. Environmental durability diagnostic for printed identification codes of polymer insulation for distribution pipelines

    Science.gov (United States)

    Zhuravleva, G. N.; Nagornova, I. V.; Kondratov, A. P.; Bablyuk, E. B.; Varepo, L. G.

    2017-08-01

    A research and modelling of weatherability and environmental durability of multilayer polymer insulation of both cable and pipelines with printed barcodes or color identification information were performed. It was proved that interlayer printing of identification codes in distribution pipelines insulation coatings provides high marking stability to light and atmospheric condensation. This allows to carry out their distant damage control. However, microbiological fouling of upper polymer layer hampers the distant damage pipelines identification. The color difference values and density changes of PE and PVC printed insolation due to weather and biological factors were defined.

  8. Identification and assessment of geohazards affecting pipelines and urban areas

    Science.gov (United States)

    Strokova, L. A.; Teterin, E. A.

    2016-09-01

    The paper addresses methods and criteria of risk assessment associated with land subsidence threatening pipelines, buildings, and constructions. Currently, there are some practical issues relating to geohazards that should be taken into account while constructing a pipeline. The article provides comparison data on the effects of Spitak earthquake and the natural disaster in Neftegorsk in terms of geohazards impact on the pipeline systems. The suggested risk assessment procedure embraces a wide range of aspects: from soil properties to economic and management issues.

  9. Identification of phenothiazine antihistamines and their metabolites in urine.

    Science.gov (United States)

    Maurer, H; Pfleger, K

    1988-01-01

    Identification of the phenothiazine antihistamines alimemazine, dimetotiazine, isothipendyl, mequitazine, oxomemazine, promethazine, thiethylperazine, triflupromazine and their metabolites in urine is described. After acid hydrolysis of the conjugates, extraction and acetylation the urine samples were analysed by computerized gas chromatography-mass spectrometry. Using ion chromatography with the selective ions m/z 58, 72, 100, 114, 124, 128, 141, and 199 the possible presence of phenothiazine antihistamines and/or their metabolites was indicated. The identity of positive signals in the reconstructed ion chromatograms was confirmed by a visual or computerized comparison of the stored full mass spectra with the reference spectra. The ion chromatograms, reference mass spectra and gas chromatographic retention indices (OV-101) are documented. The procedure presented is integrated in a general screening procedure (general unknown analysis) for several groups of drugs.

  10. Metabolism of metofluthrin in rats: I. Identification of metabolites.

    Science.gov (United States)

    Abe, Jun; Nagahori, Hirohisa; Tarui, Hirokazu; Tomigahara, Yoshitaka; Isobe, Naohiko

    2017-02-05

    1. Metofluthrin (2,3,5,6-tetrafluoro-4-(methoxymethyl)benzyl (Z/E)-(1R)-trans-2,2-dimethyl-3-(1-propenyl)-cyclopropanecarboxylate) is a novel pyrethroid insecticide, which has E/Z isomers at prop-1-enyl group. 2. Rats were orally dosed with each [(14)C]-labelled E/Z isomer, and the excreta were collected for isolation and identification of metabolites. Analysis of the excreta by LC/MS and NMR revealed formation of 33 and 23 (total 42) metabolites from rats dosed with Z-isomer and E-isomer, respectively. 3. Major metabolic reactions were cleavage of ester linkage, O-demethylation, hydroxylation, epoxidation or reduction of double bond, glutathione conjugation and its further metabolism, hydroxylation of epoxide and formation of lactone ring. Notably, the acid side, 2,2-dimethyl-3-(1-propenyl)-cyclopropanecarboxylic acid, was much more variously metabolised compared to chrysanthemic acid, the acid side of the known pyrethroids. 4. Major metabolites for Z-isomer mostly retained ester linkage with 1,2-dihydroxypropyl group and/or 2-methylalcohol of cyclopropane ring, while most of those for E-isomer received hydrolysis of the ester linkage without oxidation at the 1-propenyl group or the gem-methyl groups, suggesting epoxidation and hydroxylation could occur more easily on Z-isomer. 5. As the novel metabolic pathways for pyrethroids, isomerisation of ω-carboxylic acid moiety, reduction or hydration of double bond and cleavage of cyclopropane ring via epoxidation were suggested.

  11. The AIRS Applications Pipeline, from Identification to Visualization to Distribution

    Science.gov (United States)

    Ray, S. E.; Pagano, T. S.; Fetzer, E. J.; Lambrigtsen, B.; Teixeira, J.

    2014-12-01

    The Atmospheric Infrared Sounder (AIRS) on NASA's Aqua spacecraft has been returning daily global observations of Earth's atmospheric constituents and properties since 2002. AIRS provides observations of temperature and water vapor along the atmospheric column and is sensitive to many atmospheric constituents in the mid-troposphere, including carbon monoxide, carbon dioxide and ozone. With a 12-year data record and daily, global observations in near real-time, we are finding that AIRS data can play a role in applications that fall under most of the NASA Applied Sciences focus areas. Currently in development are temperature inversion maps that can potentially correlate to respiratory health problems, dengue fever and West Nile virus outbreak prediction maps, maps that can be used to make assessments of air quality, and maps of volcanic ash burden. This poster will communicate the Project's approach and efforts to date of its applications pipeline, which includes identifying applications, utilizing science expertise, hiring outside experts to assist with development and dissemination, visualization along application themes, and leveraging existing NASA data frameworks and organizations to facilitate archiving and distribution. In addition, a new web-based browse tool being developed by the AIRS Project for easy access to application product imagery will also be described.

  12. Identification of partial blockages in pipelines using genetic algorithms

    Indian Academy of Sciences (India)

    PRASHANTH REDDY HANMAIAHGARI; M ELKHOLY; CYRUS K RIAHI-NEZHAD

    2017-09-01

    A methodology to identify the partial blockages in a simple pipeline using genetic algorithms for non-harmonic flows is presented in this paper. A sinusoidal flow generated by the periodic on-and-off operation of a valve at the outlet is investigated in the time domain and it is observed that pressure variation at the valve is influenced by the opening size of blockage and its location. In this technique, the unsteady (steady oscillatory) pressure time series at only one location is required to identify two blockages. In the proposed methodology, thesolution of the governing hyperbolic PDEs of pipe flow is obtained using the method of characteristics. For any piping system similar to the hypothetical pipe system used in the simulations, generalized best amplitude and best frequency of the valve operation are determined, which give maximum deviation in pressure responses for a specific blockage at different locations for a given constant-head reservoir. The generalized best amplitude and best frequency of the valve operation are also obtained for two blockages. Accuracy of the proposed methodology in identifying blockages in a hypothetical simple pipe system with increased noise in the simulated measurements is studied. A non-dimensional variable is proposed to determine whether the proposed methodology is applicable to isolate partial blockages in a piping system. Finally, the proposed methodology is experimentally validated on a laboratory piping system for a single blockage and two blockages.

  13. Emerging technologies, recent developments, and novel applications for drug metabolite identification.

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    Lu, Wenjie; Xu, Youzhi; Zhao, Yinglan; Cen, Xiaobo

    2014-01-01

    Drug metabolite identification and metabolic characteristics analysis play a crucial role in new drug research and development, because they can lead to varied efficacy, severe adverse reactions, and even toxicity. Classical methodologies for metabolite identification have mainly been based on mass spectrometry (MS) coupled with gas chromatography (GC) or liquid chromatography (LC), and some other techniques are used as complementary approaches, such as nuclear magnetic resonance (NMR). Over the past decade, more and more newly emerging techniques or technologies have been applied to metabolite identification, and are making the procedure easier and more robust, such as LC-NMR-MS, ion mobility MS, ambient ionization techniques, and imaging MS. A novel application of drug metabolite identification based on "omics" known as pharmacometabonomics is discussed, which is an interdisciplinary field that combines pre-dose metabolite profiling and chemometrics methods for data analysis and modeling, aiming to predict the responses of individuals to drugs.

  14. PBIT: pipeline builder for identification of drug targets for infectious diseases.

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    Shende, Gauri; Haldankar, Harshala; Barai, Ram Shankar; Bharmal, Mohammed Husain; Shetty, Vinit; Idicula-Thomas, Susan

    2016-12-30

    PBIT (Pipeline Builder for Identification of drug Targets) is an online webserver that has been developed for screening of microbial proteomes for critical features of human drug targets such as being non-homologous to human proteome as well as the human gut microbiota, essential for the pathogen's survival, participation in pathogen-specific pathways etc. The tool has been validated by analyzing 57 putative targets of Candida albicans documented in literature. PBIT integrates various in silico approaches known for drug target identification and will facilitate high-throughput prediction of drug targets for infectious diseases, including multi-pathogenic infections.

  15. An empirical Bayes model using a competition score for metabolite identification in gas chromatography mass spectrometry

    Directory of Open Access Journals (Sweden)

    Kim Seongho

    2011-10-01

    Full Text Available Abstract Background Mass spectrometry (MS based metabolite profiling has been increasingly popular for scientific and biomedical studies, primarily due to recent technological development such as comprehensive two-dimensional gas chromatography time-of-flight mass spectrometry (GCxGC/TOF-MS. Nevertheless, the identifications of metabolites from complex samples are subject to errors. Statistical/computational approaches to improve the accuracy of the identifications and false positive estimate are in great need. We propose an empirical Bayes model which accounts for a competing score in addition to the similarity score to tackle this problem. The competition score characterizes the propensity of a candidate metabolite of being matched to some spectrum based on the metabolite's similarity score with other spectra in the library searched against. The competition score allows the model to properly assess the evidence on the presence/absence status of a metabolite based on whether or not the metabolite is matched to some sample spectrum. Results With a mixture of metabolite standards, we demonstrated that our method has better identification accuracy than other four existing methods. Moreover, our method has reliable false discovery rate estimate. We also applied our method to the data collected from the plasma of a rat and identified some metabolites from the plasma under the control of false discovery rate. Conclusions We developed an empirical Bayes model for metabolite identification and validated the method through a mixture of metabolite standards and rat plasma. The results show that our hierarchical model improves identification accuracy as compared with methods that do not structurally model the involved variables. The improvement in identification accuracy is likely to facilitate downstream analysis such as peak alignment and biomarker identification. Raw data and result matrices can be found at http

  16. Identification and characterization of microbial biofilm communities associated with corroded oil pipeline surfaces.

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    Lenhart, Tiffany R; Duncan, Kathleen E; Beech, Iwona B; Sunner, Jan A; Smith, Whitney; Bonifay, Vincent; Biri, Bernadette; Suflita, Joseph M

    2014-01-01

    Microbially influenced corrosion (MIC) has long been implicated in the deterioration of carbon steel in oil and gas pipeline systems. The authors sought to identify and characterize sessile biofilm communities within a high-temperature oil production pipeline, and to compare the profiles of the biofilm community with those of the previously analyzed planktonic communities. Eubacterial and archaeal 16S rRNA sequences of DNA recovered from extracted pipeline pieces, termed 'cookies,' revealed the presence of thermophilic sulfidogenic anaerobes, as well as mesophilic aerobes. Electron microscopy and elemental analysis of cookies confirmed the presence of sessile cells and chemical constituents consistent with corrosive biofilms. Mass spectrometry of cookie acid washes identified putative hydrocarbon metabolites, while surface profiling revealed pitting and general corrosion damage. The results suggest that in an established closed system, the biofilm taxa are representative of the planktonic eubacterial and archaeal community, and that sampling and monitoring of the planktonic bacterial population can offer insight into biocorrosion activity. Additionally, hydrocarbon biodegradation is likely to sustain these communities. The importance of appropriate sample handling and storage procedures to oilfield MIC diagnostics is highlighted.

  17. An Automatic Quality Control Pipeline for High-Throughput Screening Hit Identification.

    Science.gov (United States)

    Zhai, Yufeng; Chen, Kaisheng; Zhong, Yang; Zhou, Bin; Ainscow, Edward; Wu, Ying-Ta; Zhou, Yingyao

    2016-09-01

    The correction or removal of signal errors in high-throughput screening (HTS) data is critical to the identification of high-quality lead candidates. Although a number of strategies have been previously developed to correct systematic errors and to remove screening artifacts, they are not universally effective and still require fair amount of human intervention. We introduce a fully automated quality control (QC) pipeline that can correct generic interplate systematic errors and remove intraplate random artifacts. The new pipeline was first applied to ~100 large-scale historical HTS assays; in silico analysis showed auto-QC led to a noticeably stronger structure-activity relationship. The method was further tested in several independent HTS runs, where QC results were sampled for experimental validation. Significantly increased hit confirmation rates were obtained after the QC steps, confirming that the proposed method was effective in enriching true-positive hits. An implementation of the algorithm is available to the screening community.

  18. Pipeline for the identification and classification of ion channels in parasitic flatworms.

    Science.gov (United States)

    Nor, Bahiyah; Young, Neil D; Korhonen, Pasi K; Hall, Ross S; Tan, Patrick; Lonie, Andrew; Gasser, Robin B

    2016-03-16

    Ion channels are well characterised in model organisms, principally because of the availability of functional genomic tools and datasets for these species. This contrasts the situation, for example, for parasites of humans and animals, whose genomic and biological uniqueness means that many genes and their products cannot be annotated. As ion channels are recognised as important drug targets in mammals, the accurate identification and classification of parasite channels could provide major prospects for defining unique targets for designing novel and specific anti-parasite therapies. Here, we established a reliable bioinformatic pipeline for the identification and classification of ion channels encoded in the genome of the cancer-causing liver fluke Opisthorchis viverrini, and extended its application to related flatworms affecting humans. We built an ion channel identification + classification pipeline (called MuSICC), employing an optimised support vector machine (SVM) model and using the Kyoto Encyclopaedia of Genes and Genomes (KEGG) classification system. Ion channel proteins were first identified and grouped according to amino acid sequence similarity to classified ion channels and the presence and number of ion channel-like conserved and transmembrane domains. Predicted ion channels were then classified to sub-family using a SVM model, trained using ion channel features. Following an evaluation of this pipeline (MuSICC), which demonstrated a classification sensitivity of 95.2 % and accuracy of 70.5 % for known ion channels, we applied it to effectively identify and classify ion channels in selected parasitic flatworms. MuSICC provides a practical and effective tool for the identification and classification of ion channels of parasitic flatworms, and should be applicable to a broad range of organisms that are evolutionarily distant from taxa whose ion channels are functionally characterised.

  19. Metabolite identification for mass spectrometry-based metabolomics using multiple types of correlated ion information.

    Science.gov (United States)

    Lynn, Ke-Shiuan; Cheng, Mei-Ling; Chen, Yet-Ran; Hsu, Chin; Chen, Ann; Lih, T Mamie; Chang, Hui-Yin; Huang, Ching-jang; Shiao, Ming-Shi; Pan, Wen-Harn; Sung, Ting-Yi; Hsu, Wen-Lian

    2015-02-17

    Metabolite identification remains a bottleneck in mass spectrometry (MS)-based metabolomics. Currently, this process relies heavily on tandem mass spectrometry (MS/MS) spectra generated separately for peaks of interest identified from previous MS runs. Such a delayed and labor-intensive procedure creates a barrier to automation. Further, information embedded in MS data has not been used to its full extent for metabolite identification. Multimers, adducts, multiply charged ions, and fragments of given metabolites occupy a substantial proportion (40-80%) of the peaks of a quantitation result. However, extensive information on these derivatives, especially fragments, may facilitate metabolite identification. We propose a procedure with automation capability to group and annotate peaks associated with the same metabolite in the quantitation results of opposite modes and to integrate this information for metabolite identification. In addition to the conventional mass and isotope ratio matches, we would match annotated fragments with low-energy MS/MS spectra in public databases. For identification of metabolites without accessible MS/MS spectra, we have developed characteristic fragment and common substructure matches. The accuracy and effectiveness of the procedure were evaluated using one public and two in-house liquid chromatography-mass spectrometry (LC-MS) data sets. The procedure accurately identified 89% of 28 standard metabolites with derivative ions in the data sets. With respect to effectiveness, the procedure confidently identified the correct chemical formula of at least 42% of metabolites with derivative ions via MS/MS spectrum, characteristic fragment, and common substructure matches. The confidence level was determined according to the fulfilled identification criteria of various matches and relative retention time.

  20. Identification of metabolites with anticancer properties by computational metabolomics

    Directory of Open Access Journals (Sweden)

    Bowen Nathan J

    2008-06-01

    Full Text Available Abstract Background Certain endogenous metabolites can influence the rate of cancer cell growth. For example, diacylglycerol, ceramides and sphingosine, NAD+ and arginine exert this effect by acting as signaling molecules, while carrying out other important cellular functions. Metabolites can also be involved in the control of cell proliferation by directly regulating gene expression in ways that are signaling pathway-independent, e.g. by direct activation of transcription factors or by inducing epigenetic processes. The fact that metabolites can affect the cancer process on so many levels suggests that the change in concentration of some metabolites that occurs in cancer cells could have an active role in the progress of the disease. Results CoMet, a fully automated Computational Metabolomics method to predict changes in metabolite levels in cancer cells compared to normal references has been developed and applied to Jurkat T leukemia cells with the goal of testing the following hypothesis: Up or down regulation in cancer cells of the expression of genes encoding for metabolic enzymes leads to changes in intracellular metabolite concentrations that contribute to disease progression. All nine metabolites predicted to be lowered in Jurkat cells with respect to lymphoblasts that were examined (riboflavin, tryptamine, 3-sulfino-L-alanine, menaquinone, dehydroepiandrosterone, α-hydroxystearic acid, hydroxyacetone, seleno-L-methionine and 5,6-dimethylbenzimidazole, exhibited antiproliferative activity that has not been reported before, while only two (bilirubin and androsterone of the eleven tested metabolites predicted to be increased or unchanged in Jurkat cells displayed significant antiproliferative activity. Conclusion These results: a demonstrate that CoMet is a valuable method to identify potential compounds for experimental validation, b indicate that cancer cell metabolism may be regulated to reduce the intracellular concentration of

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

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    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.

  2. Condition Identification Based on Vibration Measurements for Free Spanning Submarine Pipelines

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    Free spanning pipelines are suspended between two points on an uneven seafloor. The variations of structural conditions, such as the changes in soil property, flow velocity, axial force and span length etc., directly affect working performance of the whole submarine pipeline system. But until now few researches have focused on condition identification for free span (CIFS). A method to identify the operational conditions of free spanning submarine pipelines based on vibration measurements is proposed in this paper. Firstly, the ill-posedness of CIFS is analyzed in detail. Secondly, the framework for CIFS based on the nonlinear kernel discriminant analysis (KDA) is established. Thirdly, the internal structural characteristics of natural frequencies, normalized frequencies and frequency change ratios are studied. And then the condition feature vector for CIFS is extracted by use of the vibration measurements. Finally, the validity of the proposed approach is evaluated by a case study. The results demonstrate that the proposed approach can effectively identify each condition of free span when condition variation occurs even if under measurement noise. It is concluded that the proposed method is a promising tool for CIFS in real applications.

  3. Nuclear Magnetic Resonance Identification of New Sulfonic Acid Metabolites of Chloroacetanilide Herbicides

    Science.gov (United States)

    Morton, M.D.; Walters, F.H.; Aga, D.S.; Thurman, E.M.; Larive, C.K.

    1997-01-01

    The detection of the sulfonic acid metabolites of the chloroacetanilide herbicides acetochlor, alachlor, butachlor, propachlor, and, more recently, metolachlor in surface and ground water suggests that a common mechanism for dechlorination exists via the glutathione conjugation pathway. The identification of these herbicides and their metabolites is important due to growing public awareness and concern about pesticide levels in drinking water. Although these herbicides are regulated, little is known about the fate of their metabolites in soil. The sulfonic acid metabolites were synthesized by reaction of the parent compounds with an excess of sodium sulfite. Acetochlor, alachlor, butachlor, metolachlor, and propachlor and their sulfonic acid metabolites were studied by nuclear magnetic resonance spectroscopy and fast atom bombardment mass spectrometry. This paper provides a direct method for the preparation and characterization of these compounds that will be useful in the analysis and study of chloracetanilide herbicides and their metabolites.

  4. Identification of amygdalin and its major metabolites in rat urine by LC-MS/MS.

    Science.gov (United States)

    Ge, B Y; Chen, H X; Han, F M; Chen, Y

    2007-10-01

    Amygdalin and its metabolites in rat urine were identified using liquid chromatography-electrospray ionization (ESI) tandem ion-trap mass spectrometry. The purified rat urine sample was separated using a reversed-phase C18 column with 10 mM sodium phosphate buffer (pH 3.1) containing 30% methanol as the mobile phase, amygdalin and its metabolites were detected by on-line mass detector in selected ion monitoring (SIM) mode. The identification of the metabolites and elucidation of their structure were performed by comparing the changes in molecular masses (DeltaM), retention times and MS(2) spectral patterns of metabolites with those of parent drug. At least seven metabolites and the parent drug were found in rat urine after i.v. injection of 100 mg/kg doses of amygdalin. Among them, six metabolites were reported for the first time.

  5. A software pipeline for processing and identification of fungal ITS sequences

    Directory of Open Access Journals (Sweden)

    Kristiansson Erik

    2009-01-01

    Full Text Available Abstract Background Fungi from environmental samples are typically identified to species level through DNA sequencing of the nuclear ribosomal internal transcribed spacer (ITS region for use in BLAST-based similarity searches in the International Nucleotide Sequence Databases. These searches are time-consuming and regularly require a significant amount of manual intervention and complementary analyses. We here present software – in the form of an identification pipeline for large sets of fungal ITS sequences – developed to automate the BLAST process and several additional analysis steps. The performance of the pipeline was evaluated on a dataset of 350 ITS sequences from fungi growing as epiphytes on building material. Results The pipeline was written in Perl and uses a local installation of NCBI-BLAST for the similarity searches of the query sequences. The variable subregion ITS2 of the ITS region is extracted from the sequences and used for additional searches of higher sensitivity. Multiple alignments of each query sequence and its closest matches are computed, and query sequences sharing at least 50% of their best matches are clustered to facilitate the evaluation of hypothetically conspecific groups. The pipeline proved to speed up the processing, as well as enhance the resolution, of the evaluation dataset considerably, and the fungi were found to belong chiefly to the Ascomycota, with Penicillium and Aspergillus as the two most common genera. The ITS2 was found to indicate a different taxonomic affiliation than did the complete ITS region for 10% of the query sequences, though this figure is likely to vary with the taxonomic scope of the query sequences. Conclusion The present software readily assigns large sets of fungal query sequences to their respective best matches in the international sequence databases and places them in a larger biological context. The output is highly structured to be easy to process, although it still needs

  6. Identification of novel circulating coffee metabolites in human plasma by liquid chromatography-mass spectrometry.

    Science.gov (United States)

    Redeuil, Karine; Smarrito-Menozzi, Candice; Guy, Philippe; Rezzi, Serge; Dionisi, Fabiola; Williamson, Gary; Nagy, Kornél; Renouf, Mathieu

    2011-07-22

    This study reports a liquid chromatography-mass spectrometry method for the detection of polyphenol-derived metabolites in human plasma without enzymatic treatment after coffee consumption. Separation of available standards was achieved by reversed-phase ultra performance liquid chromatography and detection was performed by high resolution mass spectrometry in negative electrospray ionization mode. This analytical method was then applied for the identification and relative quantification of circulating coffee metabolites. A total of 34 coffee metabolites (mainly reduced, sulfated and methylated forms of caffeic acid, coumaric acid, caffeoylquinic acid and caffeoylquinic acid lactone) were identified based on mass accuracy (<4 ppm for most metabolites), specific fragmentation pattern and co-chromatography (when standard available). Among them, 19 circulating coffee metabolites were identified for the first time in human plasma such as feruloylquinic acid lactone, sulfated and glucuronidated forms of feruloylquinic acid lactone and sulfated forms of coumaric acid. Phenolic acid derivatives such as dihydroferulic acid, dihydroferulic acid 4'-O-sulfate, caffeic acid 3'-O-sulfate, dimethoxycinnamic acid, dihydrocaffeic acid and coumaric acid O-sulfate appeared to be the main metabolites circulating in human plasma after coffee consumption. The described method is a sensitive and reliable approach for the identification of coffee metabolites in biological fluids. In future, this analytical method will give more confidence in compound identification to provide a more comprehensive assessment of coffee polyphenol bioavailability studies in humans.

  7. Identification and characterization of oxidative metabolites of 1-chloropyrene.

    Science.gov (United States)

    Kakimoto, Kensaku; Nagayoshi, Haruna; Inazumi, Naoya; Tani, Atsushi; Konishi, Yoshimasa; Kajimura, Keiji; Ohura, Takeshi; Nakano, Takeshi; Tang, Ning; Hayakawa, Kazuichi; Toriba, Akira

    2015-09-21

    Polycyclic aromatic hydrocarbons (PAHs) and chlorinated PAHs (ClPAHs) are ubiquitous contaminants that bind to the aryl hydrocarbon receptor (AhR) and exhibit mutagenic potential. It is difficult to monitor human exposure levels to ClPAHs because the exposure routes are complicated, and environmental concentrations are not always correlated with the levels of PAHs. Urinary PAH metabolites are useful biomarkers for evaluating PAH exposure, and ClPAH metabolites may therefore contribute to the estimation of ClPAH exposure. One of the most abundant ClPAHs present in the environment is 1-chloropyrene (ClPyr), and urinary ClPyr metabolites have the potential to be good biomarkers to evaluate the level of exposure to ClPAHs. Since the metabolic pathways involving ClPAHs are still undetermined, we investigated the effect of human cytochrome P450 enzymes on ClPyr and identified three oxidative metabolites by liquid chromatography-tandem mass spectrometry and nuclear magnetic resonance. We found that ClPyr was metabolized most efficiently by the P450 1A1 enzyme, followed by the 1B1 and 1A2 enzymes. Similar to ClPyr, these metabolites were shown to have agonist activity for the human AhR. We detected these metabolites when ClPyr reacted with a pooled human liver S9 fraction as well as in human urine samples. These results suggest that the metabolites may be used as biomarkers to evaluate the extent of exposure to ClPAHs.

  8. Identification of Metabolites of the Fungicide Penconazole in Human Urine.

    Science.gov (United States)

    Mercadante, R; Polledri, E; Scurati, S; Moretto, A; Fustinoni, S

    2016-07-18

    Penconazole (PEN) is a fungicide used in agriculture that has been classified as hazardous to humans and the environment. The objective of this work was to identify PEN urinary metabolites in humans and propose a biomarker for PEN exposure. Five urine samples were collected from agricultural workers who worked with and were exposed to PEN. Samples were analyzed by liquid chromatography coupled with hybrid triple quadrupole-linear ion trap mass spectrometry, with the source operating in the electrospray ionization mode. Metabolites previously identified in animal studies were searched as possible metabolites in humans. Candidate metabolites were first identified by multiple reaction monitoring following the protonated molecular ions that generated the protonated triazole moiety, which is expected to be present in all PEN metabolites; second, the isotopic patterns of the molecular ions were checked for consistency with the presence of two chlorine atoms; third, the full mass spectra were evaluated for consistency with the molecular structure. Seven different oxidized metabolites were found, both in the free and glucuronide conjugate forms. The major metabolite was the monohydroxyl-derivative PEN-OH (median molar fraction approximately 0.92 as a sum of free and glucuronide conjugated form). The product of further oxidation was the carboxyl-derivate PEN-COOH (median molar fraction approximately 0.03). After hydrolysis with β-glucuronidase, the free compounds were quantified in the presence of deuterated PEN as an internal standard; PEN-OH levels ranged from 230 to 460 μg/L, and PEN-COOH levels ranged from 5.2 to 16.7 μg/L. We propose a pathway for PEN metabolism in humans and suggest PEN-OH, after hydrolysis of glucuronide conjugates, as a biomarker for monitoring human exposure to PEN.

  9. Biodegradation of clofibric acid and identification of its metabolites

    Energy Technology Data Exchange (ETDEWEB)

    Salgado, R. [REQUIMTE/CQFB, Chemistry Department, FCT, Universidade Nova de Lisboa, 2829-516 Caparica (Portugal); ESTS-IPS, Escola Superior de Tecnologia de Setubal do Instituto Politecnico de Setubal, Rua Vale de Chaves, Campus do IPS, Estefanilha, 2910-761 Setubal (Portugal); Oehmen, A. [REQUIMTE/CQFB, Chemistry Department, FCT, Universidade Nova de Lisboa, 2829-516 Caparica (Portugal); Carvalho, G. [REQUIMTE/CQFB, Chemistry Department, FCT, Universidade Nova de Lisboa, 2829-516 Caparica (Portugal); Instituto de Biologia Experimental e Tecnologica (IBET), Av. da Republica (EAN), 2784-505 Oeiras (Portugal); Noronha, J.P. [REQUIMTE/CQFB, Chemistry Department, FCT, Universidade Nova de Lisboa, 2829-516 Caparica (Portugal); Reis, M.A.M., E-mail: amr@fct.unl.pt [REQUIMTE/CQFB, Chemistry Department, FCT, Universidade Nova de Lisboa, 2829-516 Caparica (Portugal)

    2012-11-30

    Graphical abstract: Metabolites produced during clofibric acid biodegradation. Highlights: Black-Right-Pointing-Pointer Clofibric acid is biodegradable. Black-Right-Pointing-Pointer Mainly heterotrophic bacteria degraded the clofibric acid. Black-Right-Pointing-Pointer Metabolites of clofibric acid biodegradation were identified. Black-Right-Pointing-Pointer The metabolic pathway of clofibric acid biodegradation is proposed. - Abstract: Clofibric acid (CLF) is the pharmaceutically active metabolite of lipid regulators clofibrate, etofibrate and etofyllinclofibrate, and it is considered both environmentally persistent and refractory. This work studied the biotransformation of CLF in aerobic sequencing batch reactors (SBRs) with mixed microbial cultures, monitoring the efficiency of biotransformation of CLF and the production of metabolites. The maximum removal achieved was 51% biodegradation (initial CLF concentration = 2 mg L{sup -1}), where adsorption and abiotic removal mechanisms were shown to be negligible, showing that CLF is indeed biodegradable. Tests showed that the observed CLF biodegradation was mainly carried out by heterotrophic bacteria. Three main metabolites were identified, including {alpha}-hydroxyisobutyric acid, lactic acid and 4-chlorophenol. The latter is known to exhibit higher toxicity than the parent compound, but it did not accumulate in the SBRs. {alpha}-Hydroxyisobutyric acid and lactic acid accumulated for a period, where nitrite accumulation may have been responsible for inhibiting their degradation. A metabolic pathway for the biodegradation of CLF is proposed in this study.

  10. Metabolism of Dauricine and Identification of Its Main Metabolites

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    To study the metabolism of dauricine in vivo and in vitro and identify the structure of its main metabolites, urine of rats after drug administration as the samples of dauricine metabolism in vivo was studied. Rat liver S9 fraction was prepared and the oxygenation metabolism system reconstituted to perform phase I reaction of dauricine in vitro. TLC, HPLC-DAD and MS were used to analyze and identify dauricine and its main phase I metabolites in the samples. The results showed that besides the untransformed dauricine, in the urine samples there was little product of X' which had the same features of TLC, HPLC-DAD and MS as those of N-desmethyl dauricine (N-ddau). Part of dauricine could be transformed to a main metabolite X after incubating with S9 fraction in appropriate conditions. The molecular ion peak of X was m/z 611. The full scan MS2 spectrum of m/z 611 peak from S9 sample were m/z 580, m/z 566, m/z 552, m/z 206, which were same as those of N-ddau. Liver is the major organ for dauricine metabolism and part of dauricine is biotransformed by liver. The major metabolite is considered to be N-ddau.

  11. Identification of New Synthetic Cannabinoid ADB-CHMINACA (MAB-CHMINACA) Metabolites in Human Hepatocytes.

    Science.gov (United States)

    Carlier, Jeremy; Diao, Xingxing; Sempio, Cristina; Huestis, Marilyn A

    2017-03-01

    ADB-CHMINACA (MAB-CHMINACA) is a new synthetic cannabinoid with high potency and many reported adverse events and fatalities. The drug is currently scheduled in several countries in Europe and the USA. Analytical methods need to be developed to confirm ADB-CHMINACA intake for clinical and forensic programs. For many synthetic cannabinoids, parent compound is not detectable in biological samples after intake, making the detection of metabolites the only way to prove consumption. Therefore, detection of ADB-CHMINACA metabolites in biological specimens is critical. Since there are currently no published data on ADB-CHMINACA metabolism, we aimed to identify its major metabolites. Cryopreserved human hepatocytes were incubated with 10 μmol/L ADB-CHMINACA for 3 h. Incubations were analyzed with liquid chromatography on a biphenyl column, high resolution tandem mass spectrometry (orbitrap), and metabolite identification software. A reference standard of six commercially available potential metabolites was simultaneously analyzed under the same conditions to allow correct assignment of isomers. We detected ten major metabolites. Biotransformations mainly occurred at the cyclohexylmethyl tail of the compound, as also observed with structural analogs' metabolism. Minor reactions also occurred at the tert-butyl chain. Only two analytical standards of potential metabolites matched an actual metabolite detected in hepatocyte incubations. We recommend A9 (ADB-CHMINACA hydroxycyclohexylmethyl), A4 (ADB-CHMINACA 4″-hydroxycyclohexyl), and A6 (ADB-CHMINACA hydroxycyclohexylmethyl) as metabolite targets to document ADB-CHMINACA intake in clinical and forensic cases. Additionally, these results will guide analytical standard manufacturers to better provide suitable references for further studies on ADB-CHMINACA metabolism.

  12. A unique automation platform for measuring low level radioactivity in metabolite identification studies.

    Directory of Open Access Journals (Sweden)

    Joel Krauser

    Full Text Available Generation and interpretation of biotransformation data on drugs, i.e. identification of physiologically relevant metabolites, defining metabolic pathways and elucidation of metabolite structures, have become increasingly important to the drug development process. Profiling using (14C or (3H radiolabel is defined as the chromatographic separation and quantification of drug-related material in a given biological sample derived from an in vitro, preclinical in vivo or clinical study. Metabolite profiling is a very time intensive activity, particularly for preclinical in vivo or clinical studies which have defined limitations on radiation burden and exposure levels. A clear gap exists for certain studies which do not require specialized high volume automation technologies, yet these studies would still clearly benefit from automation. Use of radiolabeled compounds in preclinical and clinical ADME studies, specifically for metabolite profiling and identification are a very good example. The current lack of automation for measuring low level radioactivity in metabolite profiling requires substantial capacity, personal attention and resources from laboratory scientists. To help address these challenges and improve efficiency, we have innovated, developed and implemented a novel and flexible automation platform that integrates a robotic plate handling platform, HPLC or UPLC system, mass spectrometer and an automated fraction collector.

  13. A Unique Automation Platform for Measuring Low Level Radioactivity in Metabolite Identification Studies

    Science.gov (United States)

    Krauser, Joel; Walles, Markus; Wolf, Thierry; Graf, Daniel; Swart, Piet

    2012-01-01

    Generation and interpretation of biotransformation data on drugs, i.e. identification of physiologically relevant metabolites, defining metabolic pathways and elucidation of metabolite structures, have become increasingly important to the drug development process. Profiling using 14C or 3H radiolabel is defined as the chromatographic separation and quantification of drug-related material in a given biological sample derived from an in vitro, preclinical in vivo or clinical study. Metabolite profiling is a very time intensive activity, particularly for preclinical in vivo or clinical studies which have defined limitations on radiation burden and exposure levels. A clear gap exists for certain studies which do not require specialized high volume automation technologies, yet these studies would still clearly benefit from automation. Use of radiolabeled compounds in preclinical and clinical ADME studies, specifically for metabolite profiling and identification are a very good example. The current lack of automation for measuring low level radioactivity in metabolite profiling requires substantial capacity, personal attention and resources from laboratory scientists. To help address these challenges and improve efficiency, we have innovated, developed and implemented a novel and flexible automation platform that integrates a robotic plate handling platform, HPLC or UPLC system, mass spectrometer and an automated fraction collector. PMID:22723932

  14. A unique automation platform for measuring low level radioactivity in metabolite identification studies.

    Science.gov (United States)

    Krauser, Joel; Walles, Markus; Wolf, Thierry; Graf, Daniel; Swart, Piet

    2012-01-01

    Generation and interpretation of biotransformation data on drugs, i.e. identification of physiologically relevant metabolites, defining metabolic pathways and elucidation of metabolite structures, have become increasingly important to the drug development process. Profiling using (14)C or (3)H radiolabel is defined as the chromatographic separation and quantification of drug-related material in a given biological sample derived from an in vitro, preclinical in vivo or clinical study. Metabolite profiling is a very time intensive activity, particularly for preclinical in vivo or clinical studies which have defined limitations on radiation burden and exposure levels. A clear gap exists for certain studies which do not require specialized high volume automation technologies, yet these studies would still clearly benefit from automation. Use of radiolabeled compounds in preclinical and clinical ADME studies, specifically for metabolite profiling and identification are a very good example. The current lack of automation for measuring low level radioactivity in metabolite profiling requires substantial capacity, personal attention and resources from laboratory scientists. To help address these challenges and improve efficiency, we have innovated, developed and implemented a novel and flexible automation platform that integrates a robotic plate handling platform, HPLC or UPLC system, mass spectrometer and an automated fraction collector.

  15. Unambiguous Metabolite Identification in High-Throughput Metabolomics by Hybrid 1H-NMR/ESI-MS1 Approach

    Energy Technology Data Exchange (ETDEWEB)

    2016-10-18

    The invention improves accuracy of metabolite identification by combining direct infusion ESI-MS with one-dimensional 1H-NMR spectroscopy. First, we apply a standard 1H-NMR metabolite identification protocol by matching the chemical shift, J-coupling and intensity information of experimental NMR signals against the NMR signals of standard metabolites in a metabolomics reference libraries. This generates a list of candidate metabolites. The list contains both false positive and ambiguous identifications. The software tool (the invention) takes the list of candidate metabolites, generated from NMRbased metabolite identification, and then calculates, for each of the candidate metabolites, the monoisotopic mass-tocharge (m/z) ratios for each commonly observed ion, fragment and adduct feature. These are then used to assign m/z ratios in experimental ESI-MS spectra of the same sample. Detection of the signals of a given metabolite in both NMR and MS spectra resolves the ambiguities, and therefore, significantly improves the confidence of the identification.

  16. Identification of Penicillin G Metabolites under Various Environmental Conditions Using UHPLC-MS/MS.

    Science.gov (United States)

    Aldeek, Fadi; Canzani, Daniele; Standland, Matthew; Crosswhite, Mark R; Hammack, Walter; Gerard, Ghislain; Cook, Jo-Marie

    2016-08-10

    In this work, we investigate the stability of penicillin G in various conditions including acidic, alkaline, natural acidic matrices and after treatment of citrus trees that are infected with citrus greening disease. The identification, confirmation, and quantitation of penicillin G and its various metabolites were evaluated using two UHPLC-MS/MS systems with variable capabilities (i.e., Thermo Q Exactive Orbitrap and Sciex 6500 QTrap). Our data show that under acidic and alkaline conditions, penicillin G at 100 ng/mL degrades quickly, with a determined half-life time of approximately 2 h. Penillic acid, penicilloic acid, and penilloic acid are found to be the most abundant metabolites of penicillin G. These major metabolites, along with isopenillic acid, are found when penicillin G is used for treatment of citrus greening infected trees. The findings of this study will provide insight regarding penicillin G residues in agricultural and biological applications.

  17. Stand-off Raman spectrometer for identification of liquids in a pressurized gas pipelines.

    Science.gov (United States)

    Foster, Michael; Storey, Jonathan; Stockwell, Paul; Widdup, David

    2015-02-09

    a stand-off Raman spectrometer has been developed to make observations of liquid samples within a gas pipeline. The instrument is based on a static Fourier Transform spectrometer. The high etendue offered by the instrument enabled four liquid samples to be measured from a distance of 2.4 m within a gas pipeline. Liquids were identified with depths less than 5 mm demonstrating that the concept is viable for active pipeline measurement.

  18. Mass spectrometric screening and identification of acidic metabolites in fulvic acid fractions of contaminated groundwater.

    Science.gov (United States)

    Jobelius, Carsten; Frimmel, Fritz H; Zwiener, Christian

    2014-05-01

    The anaerobic microbial degradation of aromatic and heterocyclic compounds is a prevalent process in contaminated groundwater systems. The introduction of functional groups into the contaminant molecules often results in aromatic and heterocyclic and succinic acids. These metabolites can be used as indicators for prevailing degradation processes. Therefore, there is a strong interest in developing analytical methods for screening and identification of these metabolites. In this study, neutral loss scans (NLS) by liquid chromatography-electrospray ionization/tandem mass spectrometry with losses of CO2 (NL ∆m/z = 44) and C2H4(CO2)2 (NL ∆m/z = 116) were applied for the first time successfully to screen selectively for acidic and succinic metabolites of aromatic and heterocyclic contaminants in two fulvic acid fractions from a contaminated site and a downstream region of a tar oil-polluted groundwater. Identification of these preselected signals was performed by high-resolution mass spectrometry with a liquid chromatography-electrospray ionization quadrupole time-of-flight mass spectrometry instrument. High-resolution mass and mass fragmentation data were then compared with a list of known metabolites from a literature search or matched with chemical databases supported with in silico fragmentation. Based on authentic analytical standards, several compounds from NLS were identified (e.g., 4-hydroxy-3-methylbenzoic acid, benzylsuccinic acid, naphthyl-2-methylsuccinic acid, 2-carboxyindane, and 2-carboxybenzothiophene) and tentatively identified (e.g., benzofuranmethylsuccinic acid and dihydrocarboxybenzothiophene) as aromatic, phenolic, heterocyclic, and succinic acids. The acidic metabolites were found exclusively in the contaminated region of the aquifer which indicates active biodegradation processes and no relevant occurrence of acidic metabolites in the downstream region.

  19. Development and In silico Evaluation of Large-Scale Metabolite Identification Methods using Functional Group Detection for Metabolomics

    Directory of Open Access Journals (Sweden)

    Joshua M Mitchell

    2014-07-01

    Full Text Available Large-scale identification of metabolites is key to elucidating and modeling metabolism at the systems level. Advances in metabolomics technologies, particularly ultra-high resolution mass spectrometry enable comprehensive and rapid analysis of metabolites. However, a significant barrier to meaningful data interpretation is the identification of a wide range of metabolites including unknowns and the determination of their role(s in various metabolic networks. Chemoselective (CS probes to tag metabolite functional groups combined with high mass accuracy provide additional structural constraints for metabolite identification and quantification. We have developed a novel algorithm, Chemically Aware Substructure Search (CASS that efficiently detects functional groups within existing metabolite databases, allowing for combined molecular formula and functional group (from CS tagging queries to aid in metabolite identification without a priori knowledge. Analysis of the isomeric compounds in both Human Metabolome Database (HMDB and KEGG Ligand demonstrated a high percentage of isomeric molecular formulae (43% and 28% respectively, indicating the necessity for techniques such as CS-tagging. Furthermore, these two databases have only moderate overlap in molecular formulae. Thus, it is prudent to use multiple databases in metabolite assignment, since each major metabolite database represents different portions of metabolism within the biosphere. In silico analysis of various CS-tagging strategies under different conditions for adduct formation demonstrate that combined FT-MS derived molecular formulae and CS-tagging can uniquely identify up to 71% of KEGG and 37% of the combined KEGG/HMDB database versus 41% and 17% respectively without adduct formation. This difference between database isomer disambiguation highlights the strength of CS-tagging for non-lipid metabolite identification. However, unique identification of complex lipids still needs

  20. Facile mutant identification via a single parental backcross method and application of whole genome sequencing based mapping pipelines

    Directory of Open Access Journals (Sweden)

    Robert Silas Allen

    2013-09-01

    Full Text Available Forward genetic screens have identified numerous genes involved in development and metabolism, and remain a cornerstone of biological research. However to locate a causal mutation, the practice of crossing to a polymorphic background to generate a mapping population can be problematic if the mutant phenotype is difficult to recognise in the hybrid F2 progeny, or dependent on parental specific traits. Here in a screen for leaf hyponasty mutants, we have performed a single backcross of an Ethane Methyl Sulphonate (EMS generated hyponastic mutant to its parent. Whole genome deep sequencing of a bulked homozygous F2 population and analysis via the Next Generation EMS mutation mapping pipeline (NGM unambiguously determined the causal mutation to be a single nucleotide polymorphisim (SNP residing in HASTY, a previously characterised gene involved in microRNA biogenesis. We have evaluated the feasibility of this backcross approach using three additional SNP mapping pipelines; SHOREmap, the GATK pipeline, and the samtools pipeline. Although there was variance in the identification of EMS SNPs, all returned the same outcome in clearly identifying the causal mutation in HASTY. The simplicity of performing a single parental backcross and genome sequencing a small pool of segregating mutants has great promise for identifying mutations that may be difficult to map using conventional approaches.

  1. Ospemifene metabolism in humans in vitro and in vivo: metabolite identification, quantitation, and CYP assignment of major hydroxylations.

    Science.gov (United States)

    Tolonen, Ari; Koskimies, Pasi; Turpeinen, Miia; Uusitalo, Jouko; Lammintausta, Risto; Pelkonen, Olavi

    2013-01-01

    The metabolism of ospemifene, a novel nonsteroidal selective estrogen receptor modulator, was investigated as part of its development. Metabolite identification, tentative quantitation, and CYP assignment of ospemifene were performed in human liver microsomes or homogenate incubations and in plasma samples from volunteer humans. The potential contributions of CYP enzymes were determined by recombinant human CYPs. Metabolite identification and tentative quantification were performed by liquid chromatography-mass spectrometry. The relative abundances of metabolites produced were dependent on ospemifene concentration and liver preparation, but the largest quantities of 4- and 4'-hydroxy-ospemifene (and their glucuronides in smaller quantities) were produced in human liver microsomes at low ospemifene concentrations. Other metabolites were detected in in vitro incubation with human liver including a direct glucuronide of ospemifene and some metabolites with only minor abundance. In human plasma samples, 4-hydroxy-ospemifene was the most abundant metabolite, representing about 25% of the abundance of the parent compound. All the other metabolites detected in plasma, including 4'-hydroxy-ospemifene, represented <7% of the abundance of ospemifene. Several CYP enzymes participated in 4-hydroxylation, including CYP2C9, CYP2C19, CYP2B6, and CYP3A4, whereas CYP3A enzymes were the only ones to catalyze 4'-hydroxylation. In vitro incubations with liver preparations provided a rather reliable starting point in the search for potential metabolites in clinical settings. The in vitro metabolite profile is informative for the in vivo metabolite profile, especially regarding the major hydroxylated metabolites. However, it is anticipated that extended in vivo exposures may result in an increased production of more distal metabolites from major metabolites.

  2. The use of LC predicted retention times to extend metabolites identification with SWATH data acquisition.

    Science.gov (United States)

    Bruderer, Tobias; Varesio, Emmanuel; Hopfgartner, Gérard

    2017-07-19

    The application of predicted LC retention time to support metabolite identification was evaluated for a metabolomics MS/MS database containing 532 compounds representative for the major human metabolite classes. LC retention times could be measured for two C18 type columns using a mobile phase of pH=3.0 for positive ESI mode (n=337, 228) and pH=8.0 for negative ESI mode (n=410, 233). A QSRR modelling was applied with a small set of model compound selected based on the Kennard-Stone algorithm. The models were implemented in the R environment and can be applied to any library. The prediction model was built with two molecular descriptors, LogD2 and the molecular volume. A limited set of model compounds (LC CalMix, n=16) could be validated on two different C18 reversed phase LC columns and with comparable prediction accuracy. The CalMix can be used to compensate for different LC systems. In addition, LC retention prediction was found, in combination with SWATH-MS, to be attractive to eliminate false positive identification as well as for ranking purpose different metabolite isomeric forms. Copyright © 2017 Elsevier B.V. All rights reserved.

  3. Mass defect filter technique and its applications to drug metabolite identification by high-resolution mass spectrometry.

    Science.gov (United States)

    Zhang, Haiying; Zhang, Donglu; Ray, Kenneth; Zhu, Mingshe

    2009-07-01

    Identification of drug metabolites by liquid chromatography/mass spectrometry (LC/MS) involves metabolite detection in biological matrixes and structural characterization based on product ion spectra. Traditionally, metabolite detection is accomplished primarily on the basis of predicted molecular masses or fragmentation patterns of metabolites using triple-quadrupole and ion trap mass spectrometers. Recently, a novel mass defect filter (MDF) technique has been developed, which enables high-resolution mass spectrometers to be utilized for detecting both predicted and unexpected drug metabolites based on narrow, well-defined mass defect ranges for these metabolites. This is a new approach that is completely different from, but complementary to, traditional molecular mass- or MS/MS fragmentation-based LC/MS approaches. This article reviews the mass defect patterns of various classes of drug metabolites and the basic principles of the MDF approach. Examples are given on the applications of the MDF technique to the detection of stable and chemically reactive metabolites in vitro and in vivo. Advantages, limitations, and future applications are also discussed on MDF and its combinations with other data mining techniques for the detection and identification of drug metabolites.

  4. Identification of a nitrone as an in vitro metabolite of N-methylamphetamine.

    Science.gov (United States)

    Coutts, R T; Jones, G R; Liu, S F

    1978-06-01

    The relatively labile nitrone, alpha-methyl-(N-methylene) benzeneethanamine N-oxide was isolated from incubates of (+/-)-N-methylamphetamine with fortified liver honogenates from rats and rabbit. Identification of the nitrone was confirmed directly by gas chromatography and gas chromatography mass spectrometry and, after its conversion to isoxazolidine adducts by the action of methyl and ethyl acrylate. An authentic sample of the nitrone was synthesized unequivocally form N-hydroxyamphetamine and formaldehyde. The isomeric nitrone, N-(alpha-methylbenzeneethylidene) methylamine N-oxide, was also synthesized and its gas chromatographic and gas chromatographic mass spectrometric characteristics determined to confirm that the metabolically formed nitrone was not N-(alpha-methylbenzeneethylidene) methylamine N-oxide. Two previously unreported metabolites of (+/-)-Nmethylamphetamine, N-hydroxyamphetamine and 1-hydroxy-1-phenyl-2-propanone, were isolated from rat in vitro experiments; the latter metabolite was not produced in vitro by rabbit liver homogenates.

  5. Identification of metabolites of nerve agent VX in serum collected from a victim.

    Science.gov (United States)

    Tsuchihashi, H; Katagi, M; Nishikawa, M; Tatsuno, M

    1998-09-01

    A human serum sample collected from a victim of the Osaka VX incident was analyzed according to our developed technique for metabolites of VX. Gas chromatography-mass spectrometry (GC-MS) in full-scan electron impact and chemical ionization modes were used, and, for more reliable confirmation, GC-MS-MS was also employed. In the serum sample, both ethyl methylphosphonic acid and 2-(diisopropylamino-ethyl)methyl sulfide were detected. These results indicated that the techniques using GC-MS and GC-MS-MS were applicable to biological samples such as serum. These results also provide the first documented, unequivocal identification of the specific metabolites of VX in victim's serum and, furthermore, clarify a part of the metabolic pathway of VX in the human body.

  6. Identification and assessment of trace contaminants associated with oil and gas pipelines abandoned in place

    Energy Technology Data Exchange (ETDEWEB)

    Thorne, W.E.R.; Basso, A.C.; Dhol, S.K. [Biophilia Inc., Calgary, Alberta (Canada)

    1996-12-31

    As more Alberta oil and gas fields become depleted, attention is being given to development of economically and environmentally sound abandonment procedures. The objective of this study was to identify and assess residual internal and external contaminants associated with abandoned pipelines, particularly those to be abandoned in place. Circumstances which might increase the risk of contaminant release, and other issues relating to residual pipeline contaminants, were also identified. It was found that there are thousands of different substances which could potentially be associated with abandoned pipelines. A wide range in the potential quantities of residual contaminants was also found. Of the issues identified, the effectiveness of pipeline pigging and cleaning procedures prior to abandonment was the most critical determinant of the potential quantities of residual contaminants. However, a number of trace contaminants, such as PCBs (Polychlorinated Biphenyls) and NORMs (Naturally Occurring Radioactive Materials) may remain after thorough cleaning. A brief review of the legislation and regulations from a number of jurisdictions shows that pipeline abandonment has only recently become an issue of concern. Regulations specific to abandonment are lacking, and more general regulations and guidelines are being applied on a contaminant-specific basis, or in terms of waste disposal requirements.

  7. Rapid, Vehicle-Based Identification of Location and Magnitude of Urban Natural Gas Pipeline Leaks.

    Science.gov (United States)

    von Fischer, Joseph C; Cooley, Daniel; Chamberlain, Sam; Gaylord, Adam; Griebenow, Claire J; Hamburg, Steven P; Salo, Jessica; Schumacher, Russ; Theobald, David; Ham, Jay

    2017-04-04

    Information about the location and magnitudes of natural gas (NG) leaks from urban distribution pipelines is important for minimizing greenhouse gas emissions and optimizing investment in pipeline management. To enable rapid collection of such data, we developed a relatively simple method using high-precision methane analyzers in Google Street View cars. Our data indicate that this automated leak survey system can document patterns in leak location and magnitude within and among cities, even without wind data. We found that urban areas with prevalent corrosion-prone distribution lines (Boston, MA, Staten Island, NY, and Syracuse, NY), leaked approximately 25-fold more methane than cities with more modern pipeline materials (Burlington, VT, and Indianapolis, IN). Although this mobile monitoring method produces conservative estimates of leak rates and leak counts, it can still help prioritize both leak repairs and replacement of leak-prone sections of distribution lines, thus minimizing methane emissions over short and long terms.

  8. Grains colonised by moulds: fungal identification and headspace analysis of produced volatile metabolites

    Directory of Open Access Journals (Sweden)

    Maria Paola Tampieri

    2010-01-01

    Full Text Available The aim of this work was to verify if the headspace analysis of fungal volatile compounds produced by some species of Fusarium can be used as a marker of mould presence on maize. Eight samples of maize (four yellow maize from North Italy and four white maize from Hungary, naturally contaminated by Fusarium and positive for the presence of fumonisins, were analyzed to detect moisture content, Aw, volatile metabolites and an enumeration of viable moulds was performed by means of a colony count technique. Headspace samples were analysed using a gas-chromatograph equipped with a capillary column TR-WAX to detect volatile metabolites of moulds. Furthermore macro and microscopic examination of the colonies was performed in order to distinguish, according to their morphology, the genera of the prevalent present moulds. Prevalent mould of eight samples was Fusarium, but other fungi, like Aspergillus, Penicillum and Mucoraceae, were observed. The metabolites produced by F.graminearum and F. moniliforme were Isobutyl-acetate, 3-Methyl-1-butanol and, only at 8 days, 3-Octanone. The incubation time can affect off flavour production in consequence of the presence of other moulds. Further studies on maize samples under different conditions are needed in order to establish the presence of moulds using the count technique and through the identification of volatile compounds.

  9. MetaboHunter: an automatic approach for identification of metabolites from 1H-NMR spectra of complex mixtures

    Directory of Open Access Journals (Sweden)

    Culf Adrian

    2011-10-01

    Full Text Available Abstract Background One-dimensional 1H-NMR spectroscopy is widely used for high-throughput characterization of metabolites in complex biological mixtures. However, the accurate identification of individual compounds is still a challenging task, particularly in spectral regions with higher peak densities. The need for automatic tools to facilitate and further improve the accuracy of such tasks, while using increasingly larger reference spectral libraries becomes a priority of current metabolomics research. Results We introduce a web server application, called MetaboHunter, which can be used for automatic assignment of 1H-NMR spectra of metabolites. MetaboHunter provides methods for automatic metabolite identification based on spectra or peak lists with three different search methods and with possibility for peak drift in a user defined spectral range. The assignment is performed using as reference libraries manually curated data from two major publicly available databases of NMR metabolite standard measurements (HMDB and MMCD. Tests using a variety of synthetic and experimental spectra of single and multi metabolite mixtures show that MetaboHunter is able to identify, in average, more than 80% of detectable metabolites from spectra of synthetic mixtures and more than 50% from spectra corresponding to experimental mixtures. This work also suggests that better scoring functions improve by more than 30% the performance of MetaboHunter's metabolite identification methods. Conclusions MetaboHunter is a freely accessible, easy to use and user friendly 1H-NMR-based web server application that provides efficient data input and pre-processing, flexible parameter settings, fast and automatic metabolite fingerprinting and results visualization via intuitive plotting and compound peak hit maps. Compared to other published and freely accessible metabolomics tools, MetaboHunter implements three efficient methods to search for metabolites in manually curated

  10. Speciation and identification of tellurium-containing metabolites in garlic, Allium sativum.

    Science.gov (United States)

    Anan, Yasumi; Yoshida, Miyuki; Hasegawa, Saki; Katai, Ryota; Tokumoto, Maki; Ouerdane, Laurent; Łobiński, Ryszard; Ogra, Yasumitsu

    2013-09-01

    Tellurium (Te) is a widely used metalloid in industry because of its unique chemical and physical properties. However, information about the biological and toxicological activities of Te in plants and animals is limited. Although Te is expected to be metabolized in organisms via the same pathway as sulfur and selenium (Se), no precise metabolic pathways are known in organisms, particularly in plants. To reveal the metabolic pathway of Te in plants, garlic, a well-known Se accumulator, was chosen as the model plant. Garlic was hydroponically cultivated and exposed to sodium tellurate, and Te-containing metabolites in the water extract of garlic leaves were identified using HPLC coupled with inductively coupled plasma mass spectrometry (ICP-MS) or electrospray tandem mass spectrometry (ESI-MS-MS). At least three Te-containing metabolites were detected using HPLC-ICP-MS, and two of them were subjected to HPLC-ESI-MS-MS for identification. The MS spectra obtained by ESI-MS-MS indicated that the metabolite was Te-methyltellurocysteine oxide (MeTeCysO). Then, MeTeCysO was chemically synthesized and its chromatographic behavior matched with that of the Te-containing metabolite in garlic. The other was assigned as cysteine S-methyltellurosulfide. These results suggest that garlic can assimilate tellurate, an inorganic Te compound, and tellurate is transformed into a Te-containing amino acid, the so-called telluroamino acid. This is the first report addressing that telluroamino acid is de novo synthesized in a higher plant.

  11. pISTil: a pipeline for yeast two-hybrid Interaction Sequence Tags identification and analysis

    Directory of Open Access Journals (Sweden)

    de Chassey Benoît

    2009-10-01

    Full Text Available Abstract Background High-throughput screening of protein-protein interactions opens new systems biology perspectives for the comprehensive understanding of cell physiology in normal and pathological conditions. In this context, yeast two-hybrid system appears as a promising approach to efficiently reconstruct protein interaction networks at the proteome-wide scale. This protein interaction screening method generates a large amount of raw sequence data, i.e. the ISTs (Interaction Sequence Tags, which urgently need appropriate tools for their systematic and standardised analysis. Findings We develop pISTil, a bioinformatics pipeline combined with a user-friendly web-interface: (i to establish a standardised system to analyse and to annotate ISTs generated by two-hybrid technologies with high performance and flexibility and (ii to provide high-quality protein-protein interaction datasets for systems-level approach. This pipeline has been validated on a large dataset comprising more than 11.000 ISTs. As a case study, a detailed analysis of ISTs obtained from yeast two-hybrid screens of Hepatitis C Virus proteins against human cDNA libraries is also provided. Conclusion We have developed pISTil, an open source pipeline made of a collection of several applications governed by a Perl script. The pISTil pipeline is intended to laboratories, with IT-expertise in system administration, scripting and database management, willing to automatically process large amount of ISTs data for accurate reconstruction of protein interaction networks in a systems biology perspective. pISTil is publicly available for download at http://sourceforge.net/projects/pistil.

  12. Pharmacokinetics, bioavailability, tissue distribution, excretion, and metabolite identification of methoxyflavones in Kaempferia parviflora extract in rats.

    Science.gov (United States)

    Mekjaruskul, Catheleeya; Jay, Michael; Sripanidkulchai, Bungorn

    2012-12-01

    Kaempferia parviflora (KP) is an herbal plant in the family of Zingiberaceae. KP mainly contains methoxyflavones, especially 5,7-dimethoxyflavone (DMF), 5,7,4'-trimethoxyflavone (TMF), and 3,5,7,3',4'-pentamethoxyflavone (PMF). The present study was designed to characterize the pharmacokinetics, including bioavailability, distribution, excretion, and identification of metabolites after administration of a KP ethanolic extract. Male rats were orally or intravenously administered a 250 mg/kg concentration of a KP extract, and blood samples were obtained at selected times to determine pharmacokinetic parameters of PMF, TMF, and DMF. For distribution and excretion studies, the organs, urine, and feces samples were collected at various times after oral administration of a larger (750 mg/kg) dose of KP extract. Methoxyflavones in the biological samples were quantified by high-performance liquid chromatography-UV, and the metabolites in urine and feces were further identified by using liquid chromatography-tandem mass spectrometry. After oral administration, concentrations of the three methoxyflavones quickly approached their maximal concentration, ranging from 0.55 to 0.88 μg/ml within 1 to 2 h after administration, and then were gradually excreted with half-lives of 3 to 6 h. The methoxyflavones showed low oral bioavailability of 1 to 4%. Three methoxyflavones were detected at their highest levels in liver followed by kidney. They were also found in lung, testes, and brain. After absorption, organ distribution, and metabolism, the components of KP were mainly eliminated through urine in the forms of demethylated, sulfated, and glucuronidated products and as demethylated metabolites in the feces. The parent compounds were found to have 0.79, 1.76, and 3.10% dose recovery in urine and 1.06, 1.77, and 0.96% dose recovery in feces for PMF, TMF, and DMF, respectively. These studies are the first to describe the pharmacokinetics of KP extract to provide the information on

  13. MutAid: Sanger and NGS Based Integrated Pipeline for Mutation Identification, Validation and Annotation in Human Molecular Genetics.

    Science.gov (United States)

    Pandey, Ram Vinay; Pabinger, Stephan; Kriegner, Albert; Weinhäusel, Andreas

    2016-01-01

    Traditional Sanger sequencing as well as Next-Generation Sequencing have been used for the identification of disease causing mutations in human molecular research. The majority of currently available tools are developed for research and explorative purposes and often do not provide a complete, efficient, one-stop solution. As the focus of currently developed tools is mainly on NGS data analysis, no integrative solution for the analysis of Sanger data is provided and consequently a one-stop solution to analyze reads from both sequencing platforms is not available. We have therefore developed a new pipeline called MutAid to analyze and interpret raw sequencing data produced by Sanger or several NGS sequencing platforms. It performs format conversion, base calling, quality trimming, filtering, read mapping, variant calling, variant annotation and analysis of Sanger and NGS data under a single platform. It is capable of analyzing reads from multiple patients in a single run to create a list of potential disease causing base substitutions as well as insertions and deletions. MutAid has been developed for expert and non-expert users and supports four sequencing platforms including Sanger, Illumina, 454 and Ion Torrent. Furthermore, for NGS data analysis, five read mappers including BWA, TMAP, Bowtie, Bowtie2 and GSNAP and four variant callers including GATK-HaplotypeCaller, SAMTOOLS, Freebayes and VarScan2 pipelines are supported. MutAid is freely available at https://sourceforge.net/projects/mutaid.

  14. Neural Resilience to Traumatic Brain Injury: Identification of Bioactive Metabolites of Docosahexaenoic Acids Involved in Neuroprotection and Recovery

    Science.gov (United States)

    2015-05-01

    Lancet 1998; 352: 688–91. 22. Birch EE, Garfield S, Hoffman DR, Uauy R, Birch DG: A randomized controlled trial of early dietary supply of long- chain ...AWARD NUMBER: W81XWH-11-2-0074 TITLE: Neural Resilience to Traumatic Brain Injury: identification of Bioactive Metabolites of Docosahexaenoic Acids...REPORT TYPE Final 3. DATES COVERED 01 March, 2011 - 28 Feb 2015 4. TITLE AND SUBTITLE Neural Resilience to Traumatic Brain Injury: Identification of

  15. Various extraction and analytical techniques for isolation and identification of secondary metabolites from Nigella sativa seeds.

    Science.gov (United States)

    Liu, X; Abd El-Aty, A M; Shim, J-H

    2011-10-01

    Nigella sativa L. (black cumin), commonly known as black seed, is a member of the Ranunculaceae family. This seed is used as a natural remedy in many Middle Eastern and Far Eastern countries. Extracts prepared from N. sativa have, for centuries, been used for medical purposes. Thus far, the organic compounds in N. sativa, including alkaloids, steroids, carbohydrates, flavonoids, fatty acids, etc. have been fairly well characterized. Herein, we summarize some new extraction techniques, including microwave assisted extraction (MAE) and supercritical extraction techniques (SFE), in addition to the classical method of hydrodistillation (HD), which have been employed for isolation and various analytical techniques used for the identification of secondary metabolites in black seed. We believe that some compounds contained in N. sativa remain to be identified, and that high-throughput screening could help to identify new compounds. A study addressing environmentally-friendly techniques that have minimal or no environmental effects is currently underway in our laboratory.

  16. Identification of ionic chloroacetanilide-herbicide metabolites in surface water and groundwater by HPLC/MS using negative ion spray

    Science.gov (United States)

    Ferrer, I.; Thurman, E.M.; Barcelo, D.

    1997-01-01

    Solid-phase extraction (SPE) was combined with high-performance liquid chromatography/high-flow pneumatically assisted electrospray mass spectrometry (HPLC/ESP/MS) for the trace analysis of oxanilic and sulfonic acids of acetochlor, alachlor, and metolachlor. The isolation procedure separated the chloroacetanilide metabolites from the parent herbicides during the elution from C18 cartridges using ethyl acetate for parent compounds, followed by methanol for the anionic metabolites. The metabolites were separated chromatographically using reversed-phase HPLC and analyzed by negative-ion MS using electrospray ionization in selected ion mode. Quantitation limits were 0.01 ??g/L for both the oxanilic and sulfonic acids based on a 100-mL water sample. This combination of methods represents an important advance in environmental analysis of chloroacetanilide-herbicide metabolites in surface water and groundwater for two reasons. First, anionic chloroacetanilide metabolites are a major class of degradation products that are readily leached to groundwater in agricultural areas. Second, anionic metabolites, which are not able to be analyzed by conventional methods such as liquid extraction and gas chromatography/mass spectrometry, are effectively analyzed by SPE and high-flow pneumatically assisted electrospray mass spectrometry. This paper reports the first HPLC/MS identification of these metabolites in surface water and groundwater.

  17. Identification and quantification of bio-actives and metabolites in physiological matrices by automated HPLC-MS

    NARCIS (Netherlands)

    van Platerink, C.J.

    2010-01-01

    Identification and quantification of bio-actives and metabolites in physiological matrices by automated HPLC-MS > Food plays an important role in human health. Nowadays there is an increasing interest in the health effects of so-calles functional foods, e.g. effects on blood pressure, cholesterol le

  18. Identification and quantification of bio-actives and metabolites in physiological matrices by automated HPLC-MS

    NARCIS (Netherlands)

    van Platerink, C.J.

    2010-01-01

    Identification and quantification of bio-actives and metabolites in physiological matrices by automated HPLC-MS > Food plays an important role in human health. Nowadays there is an increasing interest in the health effects of so-calles functional foods, e.g. effects on blood pressure, cholesterol

  19. Identification of organic compounds migrating from polyethylene pipelines into drinking water

    DEFF Research Database (Denmark)

    Brocca, D.; Arvin, Erik; Mosbæk, Hans

    2002-01-01

    A study of the diffusion of organic additives from four polyethylene (PE) materials into drinking water was conducted. Various structures of organic chemicals were identified in the water extracts by means of gas chromatography–mass spectrometry analysis. Most of them presented a basic common str...... was tested under field conditions, i.e. in water samples from newly installed pipelines in a distribution system. Here, the presence of three of the compounds identified in vitro was detected. r 2002 Elsevier Science Ltd. All rights reserved....

  20. Mapping the mouse brain with rs-fMRI: An optimized pipeline for functional network identification.

    Science.gov (United States)

    Zerbi, Valerio; Grandjean, Joanes; Rudin, Markus; Wenderoth, Nicole

    2015-12-01

    The use of resting state fMRI (rs-fMRI) in translational research is a powerful tool to assess brain connectivity and investigate neuropathology in mouse models. However, despite encouraging initial results, the characterization of consistent and robust resting state networks in mice remains a methodological challenge. One key reason is that the quality of the measured MR signal is degraded by the presence of structural noise from non-neural sources. Notably, in the current pipeline of the Human Connectome Project, a novel approach has been introduced to clean rs-fMRI data, which involves automatic artifact component classification and data cleaning (FIX). FIX does not require any external recordings of physiology or the segmentation of CSF and white matter. In this study, we evaluated the performance of FIX for analyzing mouse rs-fMRI data. Our results showed that FIX can be easily applied to mouse datasets and detects true signals with 100% accuracy and true noise components with very high accuracy (>98%), thus reducing both within- and between-subject variability of rs-fMRI connectivity measurements. Using this improved pre-processing pipeline, maps of 23 resting state circuits in mice were identified including two networks that displayed default mode network-like topography. Hierarchical clustering grouped these neural networks into meaningful larger functional circuits. These mouse resting state networks, which are publicly available, might serve as a reference for future work using mouse models of neurological disorders.

  1. Identification of imine or enamine drug metabolites using online hydrogen/deuterium exchange and exact mass measurements.

    Science.gov (United States)

    Li, Austin C; Yu, Erya; Ring, Steven C; Chovan, James P

    2012-04-30

    Drug metabolites that have imine or enamine partial structures cause extra mass-to-charge (m/z) increases in online hydrogen/deuterium exchange (HDX) in addition to hydroxyl or amine protons. Online HDX and exact mass measurement were used herein to characterize this extra increase property, and to further confirm proposed metabolite structures. Metabolites of two proprietary compounds as well as two commercially available compounds were analyzed using aqueous and HDX liquid chromatography coupled with an LTQ-Orbitrap. The exact mass measurements of both the precursor ions and product ions were acquired through data-dependent acquisition and compared with theoretical values of proposed fragment ions. Analysis of exact mass measurements of metabolite product ions under both normal aqueous and HDX conditions led to the identification of the isoxazole ring opening of compound C-1, and a double-bond formation on the methylpyrrolidine ring of compound C-2 during biotransformation. In both cases, imine or enamine structures formed in the metabolites caused extra m/z increases upon HDX that contributed confirmatory information to the structure identification. The compound 3,3-diphenyl-2-ethyl-1-pyrroline also demonstrated that the methylene protons adjacent to the imine were exchanged during online HDX. The exchangeability of methylene protons adjacent to imine or enamine moieties proved to be useful to narrow down or even pinpoint the metabolism sites of parent drugs when high-resolution exact mass measurement and online HDX were used. Copyright © 2012 John Wiley & Sons, Ltd.

  2. IQMNMR: Open source software using time-domain NMR data for automated identification and quantification of metabolites in batches

    Directory of Open Access Journals (Sweden)

    Song Xu

    2011-08-01

    Full Text Available Abstract Background One of the most promising aspects of metabolomics is metabolic modeling and simulation. Central to such applications is automated high-throughput identification and quantification of metabolites. NMR spectroscopy is a reproducible, nondestructive, and nonselective method that has served as the foundation of metabolomics studies. However, the automated high-throughput identification and quantification of metabolites in NMR spectroscopy is limited by severe spectral overlap. Although numerous software programs have been developed for resolving overlapping resonances, as well as for identifying and quantifying metabolites, most of these programs are frequency-domain methods, considerably influenced by phase shifts and baseline distortions, and effective only in small-scale studies. Almost all these programs require multiple spectra for each application, and do not automatically identify and quantify metabolites in batches. Results We created IQMNMR, an R package that integrates a relaxation algorithm, digital filter, and similarity search algorithm. It differs from existing software in that it is a time-domain method; it uses not only frequency to resolve overlapping resonances but also relaxation time constants; it requires only one NMR spectrum per application; is uninfluenced by phase shifts and baseline distortions; and most important, yields a batch of quantified metabolites. Conclusions IQMNMR provides a solution that can automatically identify and quantify metabolites by one-dimensional proton NMR spectroscopy. Its time-domain nature, stability against phase shifts and baseline distortions, requirement for only one NMR spectrum, and capability to output a batch of quantified metabolites are of considerable significance to metabolic modeling and simulation. IQMNMR is available at http://cran.r-project.org/web/packages/IQMNMR/.

  3. Degradation properties and identification of metabolites of 6-Cl-PMNI in soil and water.

    Science.gov (United States)

    Wang, Yihu; Sun, Qianqian; Tian, Chunxia; Gui, Wenjun; Zhu, Guonian

    2016-03-01

    In order to provide the scientific basis for the environmental risk assessment of cycloxaprid and 6-Cl-PMNI (intermediate of cycloxaprid), the degradation properties of 6-Cl-PMNI in aerobic, anaerobic and/or sterile soil, as well as in water with different pH values at different temperature were explored under laboratory conditions using HPLC for its kinetics study and UPLC-MS/MS for the identification of its metabolites/degradation products. Fortification study showed that the recoveries of 71.4-100.5% with the maximum coefficient variation (CV) of 7.47% were obtained. The linear range was 0.1-10 mg/L with the good linearity of R(2) = 0.9990. For standard, the method LOD (limit of detection) and LOQ (limit of quantification) was 0.03 mg/L and 0.1 mg/L, respectively. Results demonstrated the good performance of the developed method. Kinetics study indicated that the degradation half-lives (t0.5) in pH 3-pH 10 buffers varied from 111.8 d to 288.8 d at 25 °C but rapidly shortened to 1.6-25.7 d at 70 °C. Good negative linear ships (R(2) ≥ 0.8423) between half life and temperature were found. 6-Cl-PMNI could be readily degraded in non-sterile soil (t0.5 0.8-7.5 d) while slowly degraded in sterile soil (t0.5 64.8-91.2 d). Three hydrolytic products and one metabolite of 6-Cl-PMNI in aerobic soil were identified. The CC olefinic bond reacted with H2O by Markovnikov Additive Reaction and the split of C-Cl were mainly proposed as the possible reaction pathway for 6-Cl-PMNI degradation in water and in soil, respectively.

  4. Pipeline engineering

    CERN Document Server

    Liu, Henry

    2003-01-01

    PART I: PIPE FLOWSINTRODUCTIONDefinition and Scope Brief History of PipelinesExisting Major PipelinesImportance of PipelinesFreight (Solids) Transport by PipelinesTypes of PipelinesComponents of PipelinesAdvantages of PipelinesReferencesSINGLE-PHASE INCOMPRESSIBLE NEWTONIAN FLUIDIntroductionFlow RegimesLocal Mean Velocity and Its Distribution (Velocity Profile)Flow Equations for One-Dimensional AnalysisHydraulic and Energy Grade LinesCavitation in Pipeline SystemsPipe in Series and ParallelInterconnected ReservoirsPipe NetworkUnsteady Flow in PipeSINGLE-PHASE COMPRESSIBLE FLOW IN PIPEFlow Ana

  5. Cross Platform Standardisation of an Experimental Pipeline for Use in the Identification of Dysregulated Human Circulating MiRNAs.

    Directory of Open Access Journals (Sweden)

    Helena Kelly

    Full Text Available Micro RNAs (miRNAs are a class of highly conserved small non-coding RNAs that play an important part in the post-transcriptional regulation of gene expression. A substantial number of miRNAs have been proposed as biomarkers for diseases. While reverse transcriptase Real-time PCR (RT-qPCR is considered the gold standard for the evaluation and validation of miRNA biomarkers, small RNA sequencing is now routinely being adopted for the identification of dysregulated miRNAs. However, in many cases where putative miRNA biomarkers are identified using small RNA sequencing, they are not substantiated when RT-qPCR is used for validation. To date, there is a lack of consensus regarding optimal methodologies for miRNA detection, quantification and standardisation when different platform technologies are used.In this study we present an experimental pipeline that takes into consideration sample collection, processing, enrichment, and the subsequent comparative analysis of circulating small ribonucleic acids using small RNA sequencing and RT-qPCR.Initially, a panel of miRNAs dysregulated in circulating blood from breast cancer patients compared to healthy women were identified using small RNA sequencing. MiR-320a was identified as the most dysregulated miRNA between the two female cohorts. Total RNA and enriched small RNA populations (<30 bp isolated from peripheral blood from the same female cohort samples were then tested for using a miR-320a RT-qPCR assay. When total RNA was analysed with this miR-320a RT-qPCR assay, a 2.3-fold decrease in expression levels was observed between blood samples from healthy controls and breast cancer patients. However, upon enrichment for the small RNA population and subsequent analysis of miR-320a using RT-qPCR, its dysregulation in breast cancer patients was more pronounced with an 8.89-fold decrease in miR-320a expression. We propose that the experimental pipeline outlined could serve as a robust approach for the

  6. Rapid metabolite discovery, identification, and accurate comparison of the stereoselective metabolism of metalaxyl in rat hepatic microsomes.

    Science.gov (United States)

    Wang, Xinru; Qiu, Jing; Xu, Peng; Zhang, Ping; Wang, Yao; Zhou, Zhiqiang; Zhu, Wentao

    2015-01-28

    Metabolite identification and quantitation impose great challenges on risk assessment of agrochemicals, as many metabolite standards are generally unavailable. In this study, metalaxyl metabolites were identified by time-of-flight mass spectrometry and semiquantified by triple quadrupole tandem mass spectrometry with self-prepared (13)C-labeled metalaxyl metabolites as internal standards. Such methodology was employed to characterize the stereoselective metabolism of metalaxyl in rat hepatic microsomes successfully. Metabolites derived from hydroxylation, demethylation, and didemethylation were identified and semiquantified. The results indicated that (+)-S-metalaxyl eliminated preferentially as the enantiomer fraction was 0.32 after 60 min incubation. The amounts of hydroxymetalaxyl and demethylmetalaxyl derived from (-)-R-metalaxyl were 1.76 and 1.82 times higher than that of (+)-S-metalaxyl, whereas didemethylmetalaxyl derived from (+)-S-metalaxyl was 1.44 times larger than that from (-)-R-metalaxyl. This study highlights a new quantitation approach for stereoselective metabolism of chiral agrochemicals and provides more knowledge on metalaxyl risk assessment.

  7. Metabolism of 4-hydroxyandrostenedione and 4-hydroxytestosterone: Mass spectrometric identification of urinary metabolites.

    Science.gov (United States)

    Kohler, Maxie; Parr, Maria K; Opfermann, Georg; Thevis, Mario; Schlörer, Nils; Marner, Franz-Josef; Schänzer, Wilhelm

    2007-03-01

    4-Hydroxyandrost-4-ene-3,17-dione is a second generation, irreversible aromatase inhibitor and commonly used as anti breast cancer medication for postmenopausal women. 4-Hydroxytestosterone is advertised as anabolic steroid and does not have any therapeutic indication. Both substances are prohibited in sports by the World Anti-Doping Agency, and, due to a considerable increase of structurally related steroids with anabolic effects offered via the internet, the metabolism of two representative candidates was investigated. Excretion studies were conducted with oral applications of 100mg of 4-hydroxyandrostenedione or 200mg of 4-hydroxytestosterone to healthy male volunteers. Urine samples were analyzed for metabolic products using conventional gas chromatography-mass spectrometry approaches, and the identification of urinary metabolites was based on reference substances, which were synthesized and structurally characterized by nuclear magnetic resonance spectroscopy and high resolution/high accuracy mass spectrometry. Identified phase-I as well as phase-II metabolites were identical for both substances. Regarding phase-I metabolism 4-hydroxyandrostenedione (1) and its reduction products 3beta-hydroxy-5alpha-androstane-4,17-dione (2) and 3alpha-hydroxy-5beta-androstane-4,17-dione (3) were detected. Further reductive conversion led to all possible isomers of 3xi,4xi-dihydroxy-5xi-androstan-17-one (4, 6-11) except 3alpha,4alpha-dihydroxy-5beta-androstan-17-one (5). Out of the 17beta-hydroxylated analogs 4-hydroxytestosterone (18), 3beta,17beta-dihydroxy-5alpha-androstan-4-one (19), 3alpha,17beta-dihydroxy-5beta-androstan-4-one (20), 5alpha-androstane-3beta,4beta,17beta-triol (21), 5alpha-androstane-3alpha,4beta,17beta-triol (26) and 5alpha-androstane-3alpha,4alpha,17beta-triol (28) were identified in the post administration urine specimens. Furthermore 4-hydroxyandrosta-4,6-diene-3,17-dione (29) and 4-hydroxyandrosta-1,4-diene-3,17-dione (30) were determined as

  8. SRIdent: A novel pipeline for real-time identification of species from high-throughput sequencing reads in Metagenomics and clinical diagnostic assays.

    Science.gov (United States)

    Karimi, Ramin; Hajdu, Andras

    2015-01-01

    New advances in rapid sequencing of large amounts of DNA have brought a great potential for the study of complex communities of microorganisms. One of the challenging problems is rapid identification of species from sequenced reads. Delays in the identification of pathogens are a barrier to the early diagnosis and proper treatment of infectious diseases. In this paper we proposed SRIdent (Short Read Identifier), an effective pipeline for real-time identification of species from high-throughput sequencing reads in Metagenomics and clinical diagnostic assays. This pipeline is based on generating k-mers from the short reads and searching the existence of DNA signatures in the Reads k-mers, by using Apache Hive data-warehousing. RkmerG (Read k-mers Generator) is a software program presented in this paper, for producing k-mers of the short reads, in order to use in the pipeline. The purpose of this study is to identify the species in a sample, directly from the reads without assembling and alignment.

  9. Chemical Screening Method for the Rapid Identification of Microbial Sources of Marine Invertebrate-Associated Metabolites

    Directory of Open Access Journals (Sweden)

    Russell G. Kerr

    2011-03-01

    Full Text Available Marine invertebrates have proven to be a rich source of secondary metabolites. The growing recognition that marine microorganisms associated with invertebrate hosts are involved in the biosynthesis of secondary metabolites offers new alternatives for the discovery and development of marine natural products. However, the discovery of microorganisms producing secondary metabolites previously attributed to an invertebrate host poses a significant challenge. This study describes an efficient chemical screening method utilizing a 96-well plate-based bacterial cultivation strategy to identify and isolate microbial producers of marine invertebrate-associated metabolites.

  10. MetaboMiner – semi-automated identification of metabolites from 2D NMR spectra of complex biofluids

    Directory of Open Access Journals (Sweden)

    Tang Peter

    2008-11-01

    Full Text Available Abstract Background One-dimensional (1D 1H nuclear magnetic resonance (NMR spectroscopy is widely used in metabolomic studies involving biofluids and tissue extracts. There are several software packages that support compound identification and quantification via 1D 1H NMR by spectral fitting techniques. Because 1D 1H NMR spectra are characterized by extensive peak overlap or spectral congestion, two-dimensional (2D NMR, with its increased spectral resolution, could potentially improve and even automate compound identification or quantification. However, the lack of dedicated software for this purpose significantly restricts the application of 2D NMR methods to most metabolomic studies. Results We describe a standalone graphics software tool, called MetaboMiner, which can be used to automatically or semi-automatically identify metabolites in complex biofluids from 2D NMR spectra. MetaboMiner is able to handle both 1H-1H total correlation spectroscopy (TOCSY and 1H-13C heteronuclear single quantum correlation (HSQC data. It identifies compounds by comparing 2D spectral patterns in the NMR spectrum of the biofluid mixture with specially constructed libraries containing reference spectra of ~500 pure compounds. Tests using a variety of synthetic and real spectra of compound mixtures showed that MetaboMiner is able to identify >80% of detectable metabolites from good quality NMR spectra. Conclusion MetaboMiner is a freely available, easy-to-use, NMR-based metabolomics tool that facilitates automatic peak processing, rapid compound identification, and facile spectrum annotation from either 2D TOCSY or HSQC spectra. Using comprehensive reference libraries coupled with robust algorithms for peak matching and compound identification, the program greatly simplifies the process of metabolite identification in complex 2D NMR spectra.

  11. Combined data mining strategy for the systematic identification of sport drug metabolites in urine by liquid chromatography time-of-flight mass spectrometry.

    Science.gov (United States)

    Domínguez-Romero, Juan C; García-Reyes, Juan F; Martínez-Romero, Rubén; Berton, Paula; Martínez-Lara, Esther; Del Moral-Leal, María L; Molina-Díaz, Antonio

    2013-01-25

    The development of comprehensive methods able to tackle with the systematic identification of drug metabolites in an automated fashion is of great interest. In this article, a strategy based on the combined use of two complementary data mining tools is proposed for the screening and systematic detection and identification of urinary drug metabolites by liquid chromatography full-scan high resolution mass spectrometry. The proposed methodology is based on the use of accurate mass extraction of diagnostic ions (compound-dependent information) from in-source CID fragmentation without precursor ion isolation along with the use of automated mass extraction of accurate-mass shifts corresponding to typical biotransformations (non compound-dependent information) that xenobiotics usually undergo when metabolized. The combined strategy was evaluated using LC-TOFMS with a suite of nine sport drugs representative from different classes (propranolol, bumetanide, clenbuterol, ephedrine, finasteride, methoxyphenamine, methylephedrine, salbutamol and terbutaline), after single doses administered to rats. The metabolite identification coverage rate obtained with the systematic method (compared to existing literature) was satisfactory, and provided the identification of several non-previously reported metabolites. In addition, the combined information obtained helps to minimize the number of false positives. As an example, the systematic identification of urinary metabolites of propranolol enabled the identification of up to 24 metabolites, 15 of them non previously described in literature, which is a valuable indicator of the usefulness of the proposed systematic procedure.

  12. The genetic-algorithm-enhanced blind system identification for water distribution pipeline leak detection

    Science.gov (United States)

    Yang, Jin; Wen, Yumei; Li, Ping

    2007-07-01

    The conventional leak location is based on the correlation of leak acoustic signals acquired spatially separately. By correlation, the time lag is estimated for localizing the leakage. In these methods, the detection distance is a prerequisite that has to be known beforehand. However, in practice, this prerequisite is not always satisfied. In this case, the correlation-based methods are not feasible. Actually, the acquired signals contain the characteristics related to the acoustic propagation channels; thus the blind system identification strategy is applied to estimate the transmission performances of acoustic channels. Then the times due to the propagation of the leak source signal travelling from the leak point to sensors are determined. In this way, for leak location, the detection distance is no longer a prerequisite. In blind system identification, due to the long impulse responses of the leak acoustic channels, the channels are inevitably ill conditioned and sensitive to the initial values. To overcome the ill conditions, the overlap-save and cross-correlation fitting techniques are utilized to identify the long impulse sequences under a built constraint. In order to avoid converging to the local minima, the genetic algorithm is used to minimize the cost functions. The practical detection results show the validity of the proposed scheme.

  13. A sparse sensor network topologized for cylindrical wave-based identification of damage in pipeline structures

    Science.gov (United States)

    Wang, Qiang; Hong, Ming; Su, Zhongqing

    2016-07-01

    A sparse sensor network, based on the concept of semi-decentralized and standardized sensing, is developed, to actively excite and acquire cylindrical waves for damage identification and health monitoring of pipe structures. Differentiating itself from conventional ‘ring-style’ transducer arrays which attempt to steer longitudinal axisymmetric cylindrical waves via transducer synchronism, this sparse sensor network shows advantages in some aspects, including the use of fewer sensors, simpler manipulation, quicker configuration, less mutual dependence among sensors, and an improved signal-to-noise ratio. The sparse network is expanded topologically, aimed at eliminating the presence of ‘blind zones’ and the challenges associated with multi-path propagation of cylindrical waves. Theoretical analysis is implemented to comprehend propagation characteristics of waves guided by a cylindrical structure. A probability-based diagnostic imaging algorithm is introduced to visualize damage in pixelated images in an intuitive, prompt, and automatic manner. A self-contained health monitoring system is configured for experimental validation, via which quantitative identification of mono- and multi-damage in a steel cylinder is demonstrated. The results highlight an expanded sensing coverage of the sparse sensor network and its enhanced capacity of acquiring rich information, avoiding the cost of augmenting the number of sensors in a sensor network.

  14. Identification of Secondary Metabolites Compounds and Antibacterial Activities on The Extract of Soursop Leaf

    Directory of Open Access Journals (Sweden)

    Dian Riana Ningsih

    2016-05-01

    Full Text Available Treatment of bacterial infectious diseases using semi-synthetic antibiotics can lead to resistance, so as to overcome it necessary to search for natural ingredients from plant extracts that has potential as an antibacterial, one of which is the leaf extract of soursop (Annona muricata L.. This study aims to determine the antibacterial activity of soursop leaf against E. coli and identify groups most active chemical compounds from the extracts. Soursop leaves extracted by maceration using n-hexane, chloroform and methanol. The extracts were tested for antibacterial activity using the diffusion method. Extract with the highest activity determined the minimum inhibitory concentrations grow (MIC and tested the content of secondary metabolites with phytochemical test, subsequently identified using IR spectrophotometer. Soursop leaves with extraction solvent n-hexane, chloroform and methanol to produce n-hexane extract (E1, the chloroform extract (E2, and the methanol extract (E3 with a yield respectively 0.82%; 5.21%; 8.2% and produce antibacterial activity with consecutive inhibition zone of 3.52 mm; 8.34 mm; 3.00 mm. MIC of soursop leaf chloroform extract of the E. coli bacteria that is at a concentration of 1 ppm with inhibition zone of 3.23 mm. Based on the test results phytochemical soursop leaf chloroform extract showed the presence of compounds alkaloids, steroids, saponins and tannins. IR spectrophotometer identification results showed that the chloroform extract of the leaves of the soursop has functional groups OH, aliphatic C-H, C = O, C = C aromatic, CH3, C-O ether and C-H outside the field.

  15. Sensomics mapping and identification of the key bitter metabolites in Gouda cheese.

    Science.gov (United States)

    Toelstede, Simone; Hofmann, Thomas

    2008-04-23

    Application of a sensomics approach on the water-soluble extract of a matured Gouda cheese including gel permeation chromatography, ultrafiltration, solid phase extraction, preparative RP-HPLC, and HILIC combined with analytical sensory tools enabled the comprehensive mapping of bitter-tasting metabolites. LC-MS-TOF and LC-MS/MS, independent synthesis, and sensory analysis revealed the identification of a total of 16 bitter peptides formed by proteolysis of caseins. Eleven previously unreported bitter peptides were aligned to beta-casein, among which 6 peptides were released from the sequence beta-CN(57-69) of the N terminus of beta-casein and 2 peptides originated from the C-terminal sequence beta-CN(198-206). The other peptides were liberated from miscellaneous regions of beta-casein, namely, beta-CN(22-28), beta-CN(74-86), beta-CN(74-77), and beta-CN(135-138), respectively. Six peptides were found to originate from alpha(s1)-casein and were shown to have the sequences alpha(s1)-CN(11-14), alpha(s1)-CN(56-60), alpha(s1)-CN(70/71-74), alpha(s1)-CN(110/111-114), and alpha(s1)-CN(135-136). Sensory evaluation of the purified, synthesized peptides revealed that 12 of these peptides showed pronounced bitter taste with recognition thresholds between 0.05 and 6.0 mmol/L. Among these peptides, the decapeptide YPFPGPIHNS exhibited a caffeine-like bitter taste quality at the lowest threshold concentration of 0.05 mmol/L.

  16. In silico fragmentation for computer assisted identification of metabolite mass spectra

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    Müller-Hannemann Matthias

    2010-03-01

    Full Text Available Abstract Background Mass spectrometry has become the analytical method of choice in metabolomics research. The identification of unknown compounds is the main bottleneck. In addition to the precursor mass, tandem MS spectra carry informative fragment peaks, but the coverage of spectral libraries of measured reference compounds are far from covering the complete chemical space. Compound libraries such as PubChem or KEGG describe a larger number of compounds, which can be used to compare their in silico fragmentation with spectra of unknown metabolites. Results We created the MetFrag suite to obtain a candidate list from compound libraries based on the precursor mass, subsequently ranked by the agreement between measured and in silico fragments. In the evaluation MetFrag was able to rank most of the correct compounds within the top 3 candidates returned by an exact mass query in KEGG. Compared to a previously published study, MetFrag obtained better results than the commercial MassFrontier software. Especially for large compound libraries, the candidates with a good score show a high structural similarity or just different stereochemistry, a subsequent clustering based on chemical distances reduces this redundancy. The in silico fragmentation requires less than a second to process a molecule, and MetFrag performs a search in KEGG or PubChem on average within 30 to 300 seconds, respectively, on an average desktop PC. Conclusions We presented a method that is able to identify small molecules from tandem MS measurements, even without spectral reference data or a large set of fragmentation rules. With today's massive general purpose compound libraries we obtain dozens of very similar candidates, which still allows a confident estimate of the correct compound class. Our tool MetFrag improves the identification of unknown substances from tandem MS spectra and delivers better results than comparable commercial software. MetFrag is available through a web

  17. Metabolites of tamoxifen in animals and man: identification, pharmacology, and significance.

    Science.gov (United States)

    Jordan, V C

    1982-01-01

    Over the past decade, the non-steroidal antiestrogen tamoxifen has gained general acceptance for the palliative treatment of breast cancer. Although there has been much interest in the pharmacology of tamoxifen, our knowledge of its metabolism in laboratory animals and patients is incomplete and the precise mechanism of action within target tissue and breast tumor cells is unknown. This review briefly describes the pharmacology of tamoxifen in various laboratory species and patients. Several metabolites of tamoxifen are known and their relative potencies as estrogens and antiestrogens are compared with the parent compound. Apart from monohydroxytamoxifen, none of tamoxifen's metabolites are more potent antiestrogens, but a metabolite in the dog, Metabolite E, is fully estrogenic. Routine assays (tlc, HPLC, glc/ms) are available to detect tamoxifen, N-desmethyltamoxifen, monohydroxytamoxifen, and a newly identified metabolite, designated Metabolite Y, in biological fluids. Continuous therapy with tamoxifen (10 mg bid) produces steady-state levels (100-200 ng/ml serum) within 4 weeks. Levels of N-desmethyltamoxifen are often up to twice the levels achieved with tamoxifen, while levels of monohydroxytamoxifen and Metabolite Y are below 10 ng/ml. Although monohydroxytamoxifen has a high binding affinity for the estrogen receptor, the metabolic activation of tamoxifen is an advantage rather than a requirement for antiestrogenic activity. The action of tamoxifen in vivo is the net result of the individual actions of the parent compound and its metabolites competing for the occupation of receptors within target tissues and tumors.

  18. Identification of bupropion urinary metabolites by liquid chromatography/mass spectrometry.

    Science.gov (United States)

    Petsalo, Aleksanteri; Turpeinen, Miia; Tolonen, Ari

    2007-01-01

    Human urinary metabolism of the antidepressant bupropion was studied using liquid chromatography/time-of-flight mass spectrometry (LC/TOFMS) and liquid chromatography/tandem mass spectrometry (LC/MS/MS). A total of 20 metabolites were detected and identified. The phase I metabolism included formation of morpholinohydroxybupropion, threo- and erythrohydrobupropion, aromatic hydroxylation, butyl group hydroxylation with ketone hydrogenation and dihydroxylation. These metabolites were detected either as the free form or as glucuronide and/or sulphate conjugates. In addition also m-chlorohippuric acid was detected. Of the phase I metabolites, a dihydroxylation to the aromatic ring and to the methyl group in the middle of the substrate molecule was reported here for the first time, as well as eight of the glucuronide conjugates (to hydroxy, dihydroxy, hydroxy and hydrogenation metabolites) and three of the sulphate conjugates (to aromatic hydroxy and hydroxy and hydrogenation metabolites). Copyright (c) 2007 John Wiley & Sons, Ltd.

  19. Metabolic profiling identification of metabolites formed in Mediterranean mussels (Mytilus galloprovincialis) after diclofenac exposure.

    Science.gov (United States)

    Bonnefille, Bénilde; Arpin-Pont, Lauren; Gomez, Elena; Fenet, Hélène; Courant, Frédérique

    2017-04-01

    Despite the growing concern on the presence of pharmaceutically active compounds in the environment, few studies have been conducted on their metabolism in marine organisms. In this study, a non-targeted strategy based on the generation of chemical profiles generated by liquid chromatography combined with high resolution mass spectrometry was used to highlight metabolite production by the Mediterranean mussel (Mytilus galloprovincialis) after diclofenac exposure. This method allowed revealing the production of 13 metabolites in mussel tissues. Three of them were phase I metabolites, including 4'-hydroxy-diclofenac and 5-hydroxy-diclofenac. The remaining 10 were phase II metabolites, including sulfate and amino acids conjugates. Among all of the metabolites highlighted, 5 were reported for the first time in an aquatic organism exposed to diclofenac.

  20. Metabolism of cycloate in radish leaf: metabolite identification by packed capillary flow fast atom bombardment tandem mass spectrometry.

    Science.gov (United States)

    Onisko, B C; Barnes, J P; Staub, R E; Walker, F H; Kerlinger, N

    1994-10-01

    The metabolism of cycloate, a thiocarbamate herbicide, was investigated in mature radish leaf. Twelve new metabolites were identified by liquid chromatographic/mass spectrometric analysis using fast atom bombardment and packed capillary liquid chromatography columns. Full-scan and tandem mass spectrometric methods were employed. Application of the on-column focusing technique resulted in identifications with injections of as little as 15 ng of metabolite (20 ppb in radish). This injection technique allows the practical use of packed capillary liquid chromatography/mass spectrometry in sample-limited applications. Cycloate is oxidized to several ring-hydroxylated isomers that are subsequently glucosylated and esterified with malonic acid. Cycloate is also conjugated with glutathione. Metabolic hydrolysis of the glutathione conjugate formed a cysteine conjugate that is further metabolized by amidation with either malonic or acetic acid. Transamination of the cysteine conjugate gave a thiolactic acid derivative. Metabolites were also identified that were the result of both ring-hydroxylation and conjugation with glutathione. One of these, an N-acetylcysteine conjugate, is the first report of a mercapturic acid in plants. The structures of two of the new metabolites were confirmed by chemical synthesis.

  1. Identification of some benproperine metabolites in humans and investigation of their antitussive effect

    Institute of Scientific and Technical Information of China (English)

    Yan LI; Da-fang ZHONG; Si-wei CHEN; Isamu MAEBA

    2005-01-01

    Aim: To identify 4 unknown metabolites of benproperine (BPP, 1) in human urine after a po dose, and to investigate the antitussive effect of monohydroxylate metabolites. Methods: The putative metabolite references were prepared using chemical synthesis. Their structures were identified using 1H and 13C nuclear magnetic resonance, and mass spectrometry. The metabolites in human urine were separated and assayed using liquid chromatography-ion trap mass spectrometry (LC/MS/MS), and further confirmed by comparison of their mass spectra and chromatographic retention times with those of synthesized reference substances. The antitussive effects of metabolites were evaluated on coughs induced by 7.5% citric acid in conscious guinea pigs. Results: 1-[1-Methyl-2-[2-(phenylmethyl)phenoxy] -ethyl] -4-piperidinol (2), 1- [ 1-methyl-2- [2-(phenylmethyl)phenoxy] ethyl]-3-piperidinol (3) and their glucuronides 4 and 5 were obtained from chemical synthesis. Four urinary metabolites in human urine showed peaks with the same chromatographic retention times and mass spectra in LC/MS/MS as synthetic substances 2, 3, 4 and 5. Phosphates of compounds 2 and 3 prolonged the latency of cough and reduced the number of coughs during the 3 min test using citric acid, but did not reduce the number of coughs during the 5 min immediately after the test in conscious guinea pigs. Conclusion: Compounds 2, 3, 4,and 5 were identified as the metabolites of BPP in human urine. Among them,compounds 2 and 3 are inactive in the antitussive effect.

  2. Identification of a Solanum pennellii Chromosome 4 Fruit Flavor and Nutritional Quality-Associated Metabolite QTL

    Directory of Open Access Journals (Sweden)

    ZHONGYUAN LIU

    2016-11-01

    Full Text Available A major resource for tomato quality improvement and gene discovery is the collection of introgression lines (ILs of cultivated Solanum lycopersicum that contain different, defined chromosomal segments derived from the wild tomato relative, S. pennellii. Among these lines, IL4-4, in which the bottom of S. lycopersicum (cv. M82 chromosome 4 is replaced by the corresponding S. pennellii segment, is altered in many primary and secondary metabolites, including many related to fruit flavor and nutritional quality. Here, we provide a comprehensive profile of IL4-4 ripe fruit metabolites, the transcriptome and fine mapping of sub-ILs. Remarkably, out of 327 quantified metabolites, 185 were significantly changed in IL4-4 fruit, compared to the control. These altered metabolites include volatile organic compounds, primary and secondary metabolites. Partial least squares enhanced discriminant analysis of the metabolite levels among sub-ILs indicated that a genome region encompassing 20 putative open reading frames is responsible for most of the metabolic changes in IL4-4 fruit. This work provides comprehensive insights into IL4-4 fruit biochemistry, identifying a small region of the genome that has major effects on a large and diverse set of metabolites.

  3. Identification of rat faecal metabolites of ebastine by B/E linked scanning liquid secondary ion mass spectrometry.

    Science.gov (United States)

    Yoshida, K; Hatoyama, T; Fujii, T; Kagemoto, A; Miyazaki, H; Naruto, S

    1994-07-01

    The identification of rat faecal metabolites of a new antihistaminic agent, ebastine, 4'-tert-butyl-4-[4-(diphenylmethoxy)piperidino]butyrophenone, is presented. After oral administration of (14C)ebastine (20 mg kg-1) to rats, 84% of the radioactive dose was excreted in the 24 h faeces. Unchanged drug and five metabolites were isolated from the faeces by thin-layer chromatography and solid-phase extraction, and their structures were identified by liquid secondary ion mass spectrometry using the B/E linked scanning technique. The main metabolic pathways were oxidation of a terminal methyl group to give the hydroxymethyl and carboxyl derivatives, and hydroxylation of a phenyl ring in the diphenylmethoxy moiety. In addition to the oxidative mechanism, metabolism of ebastine involved sulphate conjugation. It is noteworthy that M-4, having both phenolic and alcoholic hydroxyl groups, was sulphated selectively in the latter position.

  4. Microbial biotransformation of cryptotanshinone by Cunninghamella elegans and its application for metabolite identification in rat bile.

    Science.gov (United States)

    Sun, Jiang-Hao; Yang, Min; Ma, Xiao-Chi; Kang, Jie; Han, Jian; Guo, De-An

    2009-06-01

    Cryptotanshinone (1) is one of the major bioactive constituents in Salvia miltiorrhiza Bunge. Preparative-scale biotransformation of cryptotanshinone by Cunninghamella elegans (AS 3.2082) produced three new products, which were identified as (3R,15R)-3-hydroxycryptotanshinone (2), (3S,15R)-3-hydroxycryptotanshinone (3), and (4S,15R)-18-hydroxycryptotanshinone (4), respectively. The structural elucidation was based primarily on 1D and 2D NMR and HR-ESI-MS analyses. The absolute configuration of these three products was confirmed by comparison of their circular dichroism spectra with those of the known compounds. These biotransformed metabolites were used as for the comparison of in vivo metabolites in rat bile sample after intravenous administration and they are identical to three of the minor hydroxylated metabolites in vivo, which suggested that microbial biotransformation model was a useful and feasible approach for the preparation of mammalian metabolites in trace.

  5. Microbial metabolism of loganin by intestinal bacteria and identification of new metabolites in rat.

    Science.gov (United States)

    Li, Xiaona; Huo, Changhong; Wang, Qiao; Zhang, Xiaowei; Sheng, Xiaona; Zhang, Lantong

    2008-04-01

    Loganin is an important constituent of the traditional Chinese medicine Fructus Corni, with several bioactivities. Microbial metabolism of loganin by intestinal bacteria was investigated. Two metabolites (log-1 and log-2) were isolated from anaerobic culture and their structures were identified by means of their ESI-MS, (1)H-NMR, (13)C-NMR and 2D-NMR spectral data. Log-1 was an aglycone of loganin and log-2 was proved to be a new compound. In vivo metabolites of loganin were detected in rat urine, bile and feces after oral administration of loganin and the structures were proved to be identical with that of the microbial metabolites log-1 and log-2 by HPLC-PDA analysis and comparison with the reference standards. Therefore we can prepare metabolites by anaerobic culture with intestinal bacteria.

  6. Identification of urine metabolites associated with 5-year changes in biomarkers of glucose homoeostasis

    DEFF Research Database (Denmark)

    Friedrich, N.; Skaaby, T.; Pietzner, Maik

    2017-01-01

    Aim: Metabolomics provides information on pathogenetic mechanisms and targets for interventions, and may improve risk stratification. During the last decade, metabolomics studies were used to gain deeper insight into the pathogenesis of diabetes mellitus. However, longitudinal metabolomics studies...... urine metabolites were found to be associated with detrimental longitudinal changes in biomarkers of glucose homoeostasis. The identified metabolites point to mechanisms involving betaine and coffee metabolism as well as the possible influence of the gut microbiome....

  7. Identification of new flavone-8-acetic acid metabolites using mouse microsomes and comparison with human microsomes.

    Science.gov (United States)

    Pham, Minh Hien; Auzeil, Nicolas; Regazzetti, Anne; Dauzonne, Daniel; Dugay, Annabelle; Menet, Marie-Claude; Scherman, Daniel; Chabot, Guy G

    2007-11-01

    Flavone-8-acetic acid (FAA) is a potent anticancer agent in mouse but has not shown activity in humans. Because FAA metabolism could play a role in this interspecies difference, our aim was to identify the metabolites formed in vitro using mouse microsomes compared with those in human microsomes. Mouse microsomes produced six metabolites as detected by reversed-phase high-performance liquid chromatography-mass spectrometry (MS). Three metabolites were identified as the 3'-, 4'-, or 6-hydroxy-FAA, by comparison with retention times and UV and MS spectra of standards. Two metabolites presented a molecular weight of 296 (FAA = 280) indicating the presence of one oxygen but did not correspond to any monohydroxylated FAA derivative. These two metabolites were identified as epoxides because they were sensitive to epoxide hydrolase. The position of the oxygen was determined by the formation of the corresponding phenols under soft acidic conditions: one epoxide yielded the 3'- and 4'-hydroxy-FAA, thus corresponding to the 3',4'-epoxy-FAA, whereas the other epoxide yielded 5- and 6-hydroxy-FAA, thus identifying the 5,6-epoxy-FAA. The last metabolite was assigned to the 3',4'-dihydrodiol-FAA because of its molecular weight (314) and sulfuric acid dehydration that indicated that the 3'- and 4'-positions were involved. Compared with mouse microsomes, human microsomes (2 pools and 15 individual microsomes) were unable to metabolize FAA to a significant extent. In conclusion, we have identified six new FAA metabolites formed by mouse microsomes, whereas human microsomes could not metabolize this flavonoid to a significant extent. The biological importance of the new metabolites identified herein remains to be evaluated.

  8. Identification and determination of phase II nabumetone metabolites by high-performance liquid chromatography with photodiode array and mass spectrometric detection.

    Science.gov (United States)

    Nobilis, M; Holcapek, M; Kolárová, L; Kopecký, J; Kunes, M; Svoboda, Z; Kvetina, J

    2004-03-26

    Chromatographic analyses play an important role in the identification and determination of phase I and phase II drug metabolites. While the chemical standards of phase I metabolites are usually available from commercial sources or by various synthetic, degradation or isolation methods, the phase II drug metabolites have usually more complicated structures, their standards are in general inaccessible and their identification and determination require a comprehensive analytical approach involving the use of xenobiochemical methods and the employment of hyphenated analytical techniques. In this work, various high-performance liquid chromatography (HPLC) methods were employed in the evaluation of xenobiochemical experiments leading to the identification and determination of phase II nabumetone metabolites. Optimal conditions for the quantitative enzymatic deconjugation of phase II metabolites were found for the samples of minipig bile, small intestine contents and urine. Comparative HPLC analyses of the samples of above-mentioned biomatrices and of the same biomatrices after their enzymatic treatment using beta-glucuronidase and arylsulfatase afforded the qualitative and quantitative information about phase II nabumetone metabolites. Hereby, three principal phase II nabumetone metabolites (ether glucuronides) were discovered in minipig's body fluids and their structures were confirmed using liquid chromatography (LC)-electrospray ionization mass spectrometric (MS) analyses.

  9. NMR identification of endogenous metabolites interacting with fatted and non-fatted human serum albumin in blood plasma: Fatty acids influence the HSA-metabolite interaction

    Science.gov (United States)

    Jupin, Marc; Michiels, Paul J.; Girard, Frederic C.; Spraul, Manfred; Wijmenga, Sybren S.

    2013-03-01

    Metabolites and their concentrations are direct reporters on body biochemistry. Thanks to technical developments metabolic profiling of body fluids, such as blood plasma, by for instance NMR has in the past decade become increasingly accurate enabling successful clinical diagnostics. Human Serum Albumin (HSA) is the main plasma protein (∼60% of all plasma protein) and responsible for the transport of endogenous (e.g. fatty acids) and exogenous metabolites, which it achieves thanks to its multiple binding sites and its flexibility. HSA has been extensively studied with regard to its binding of drugs (exogenous metabolites), but only to a lesser extent with regard to its binding of endogenous (non-fatty acid) metabolites. To obtain correct NMR measured metabolic profiles of blood plasma and/or potentially extract information on HSA and fatty acids content, it is necessary to characterize these endogenous metabolite/plasma protein interactions. Here, we investigate these metabolite-HSA interactions in blood plasma and blood plasma mimics. The latter contain the roughly twenty metabolites routinely detected by NMR (also most abundant) in normal relative concentrations with fatted or non-fatted HSA added or not. First, we find that chemical shift changes are small and seen only for a few of the metabolites. In contrast, a significant number of the metabolites display reduced resonance integrals and reduced free concentrations in the presence of HSA or fatted HSA. For slow-exchange (or strong) interactions, NMR resonance integrals report the free metabolite concentration, while for fast exchange (weak binding) the chemical shift reports on the binding. Hence, these metabolites bind strongly to HSA and/or fatted HSA, but to a limited degree because for most metabolites their concentration is smaller than the HSA concentration. Most interestingly, fatty acids decrease the metabolite-HSA binding quite significantly for most of the interacting metabolites. We further find

  10. Identification of a sulfate metabolite of PCB 11 in human serum.

    Science.gov (United States)

    Grimm, Fabian A; Lehmler, Hans-Joachim; Koh, Wen Xin; DeWall, Jeanne; Teesch, Lynn M; Hornbuckle, Keri C; Thorne, Peter S; Robertson, Larry W; Duffel, Michael W

    2017-01-01

    Despite increasing evidence for a major role for sulfation in the metabolism of lower-chlorinated polychlorinated biphenyls in vitro and in vivo, and initial evidence for potential bioactivities of the resulting sulfate ester metabolites, the formation of PCB sulfates in PCB exposed human populations had not been explored. The primary goal of this study was to determine if PCB sulfates, and potentially other conjugated PCB derivatives, are relevant classes of PCB metabolites in the serum of humans with known exposures to PCBs. In order to detect and quantify dichlorinated PCB sulfates in serum samples of 46 PCB-exposed individuals from either rural or urban communities, we developed a high-resolution mass spectrometry-based protocol using 4-PCB 11 sulfate as a model compound. The method also allowed the preliminary analysis of these 46 human serum extracts for the presence of other metabolites, such as glucuronic acid conjugates and hydroxylated PCBs. Sulfate ester metabolites derived from dichlorinated PCBs were detectable and quantifiable in more than 20% of analyzed serum samples. Moreover, we were able to utilize this method to detect PCB glucuronides and hydroxylated PCBs, albeit at lower frequencies than PCB sulfates. Altogether, our results provide initial evidence for the presence of PCB sulfates in human serum. Considering the inability of previously employed analytical protocols for PCBs to extract these sulfate ester metabolites and the concentrations of these metabolites observed in our current study, our data support the hypothesis that total serum levels of PCB metabolites in exposed individuals may have been underestimated in the past.

  11. Biotransformation of aesculin by human gut bacteria and identification of its metabolites in rat urine

    Institute of Scientific and Technical Information of China (English)

    Wei-Jun Ding; Yun Deng; Hao Feng; Wei-Wei Liu; Rong Hu; Xiang Li; Zhe-Ming Gu; Xiao-Ping Dong

    2009-01-01

    AIM:To observe the biotransformation process of a Chinese compound, aesculin, by human gut bacteria, and to identify its metabolites in rat urine. METHODS:Representative human gut bacteria were collected from 20 healthy volunteers, and then utilized in vitro to biotransform aesculin under anaerobic conditions. At 0, 2, 4, 8, 12, 16, 24, 48 and 72 h postincubation, 10 mL of culture medium was collected. Metabolites of aesculin were extracted 3 × from rat urine with methanol and analyzed by HPLC. For in vivo metabolite analysis, aesculetin (100 mg/kg) was administered to rats via stomach gavage, rat urine was collected from 6 to 48 h post-administration, and metabolite analysis was performed by LC/ESI-MS and MS/MS in the positive and negative modes. RESULTS:Human gut bacteria could completely convert aesculin into aesculetin in vitro. The biotransformation process occurred from 8 to 24 h post-incubation, with its highest activity was seen from 8 to 12 h. The in vitro process was much slower than the in vivo process. In contrast to the in vitro model, six aesculetin metabolites were identified in rat urine, including 6-hydroxy-7-glucocoumarin (M1), 6-hydroxy-7-sulf-coumarin (M2), 6, 7-digluco- coumarin (M3), 6-glc-7-gluco-coumarin (M4), 6-O-methyl-7-gluco-coumarin (M5) and 6-O-methyl-7- sulf-coumarin (M6). Of which, M2 and M6 were novel metabolites. CONCLUSION:Aesculin can be transferred into aesculetin by human gut bacteria and is furth er modifiedby the host in vivo. The diverse metabolites of aesculin may explain its pleiotropic pharmaceutical effects.

  12. Identification of signatory secondary metabolites during mycoparasitism of Rhizoctonia solani by Stachybotrys elegans

    Directory of Open Access Journals (Sweden)

    Rony eChamoun

    2015-04-01

    Full Text Available Stachybotrys elegans is able to parasitize the fungal plant pathogen Rhizoctonia solani AG-3 following a complex and intimate interaction, which, among others, includes the production of cell wall-degrading enzymes, intracellular colonization, and expression of pathogenic process encoding genes. However, information on the metabolome level is non-existent during mycoparasitism. Here, we performed a direct-infusion mass spectrometry (DIMS metabolomics analysis using an LTQ Orbitrap analyzer in order to detect changes in the profiles of induced secondary metabolites of both partners during this mycoparasitic interaction four and five days following its establishment. The diketopiperazine(s (DKPs cyclo(S-Pro-S-Leu/cyclo(S-Pro-S-Ile, ethyl 2-phenylacetate, and 3-nitro-4-hydroxybenzoic acid were detected as the primary response of Rhizoctonia four days following dual-culturing with Stachybotrys, whereas only the latter metabolite was up-regulated one day later. On the other hand, trichothecenes and atranones were mycoparasite-derived metabolites identified during mycoparasitism four and five days following dual-culturing. All the above secondary metabolites are known to exhibit bioactivity, including fungitoxicity, and represent key elements that determine the outcome of the interaction being studied. Results could be further exploited in programs for the evaluation of the bioactivity of these metabolites per se or their chemical analogues, and/or genetic engineering programs to obtain more efficient mycoparasite strains with improved efficacy and toxicological profiles.

  13. Identification of polyphenols and their metabolites in human urine after cranberry-syrup consumption.

    Science.gov (United States)

    Iswaldi, Ihsan; Arráez-Román, David; Gómez-Caravaca, Ana María; Contreras, María Del Mar; Uberos, José; Segura-Carretero, Antonio; Fernández-Gutiérrez, Alberto

    2013-05-01

    As the beneficial effects of American cranberry (Vaccinium macrocarpon) can be partly attributed to its phenolic composition, the evaluation of the physiological behaviour of this fraction is crucial. A rapid and sensitive method by ultra-performance liquid chromatography coupled to quadrupole-time-of-flight mass spectrometry (UPLC-Q-TOF-MS) has been used to identify phenolic metabolites in human urine after a single dose of cranberry syrup. Prior to the analysis, metabolites were extracted using an optimised solid-phase extraction procedure. All possible metabolites were investigated based on retention time, accurate mass data and isotope and fragmentation patterns. Free coumaroyl hexose (isomer 1 and 2), dihydroxybenzoic acid, caffeoyl glucose, dihydroferulic acid 4-O-β-d-glucuronide, methoxyquercetin 3-O-galactoside, scopoletin, myricetin and quercetin, together with other 23 phase-I and phase-II metabolites, including various isomers, could be tentatively identified in the urine. Afterwards, the metabolites were simultaneously screened in the urine of different subjects at 0, 2, 4, and 6h after the ingestion of cranberry syrup by Target Analysis(TM) software.

  14. Identification of signatory secondary metabolites during mycoparasitism of Rhizoctonia solani by Stachybotrys elegans

    Science.gov (United States)

    Chamoun, Rony; Aliferis, Konstantinos A.; Jabaji, Suha

    2015-01-01

    Stachybotrys elegans is able to parasitize the fungal plant pathogen Rhizoctonia solani AG-3 following a complex and intimate interaction, which, among others, includes the production of cell wall-degrading enzymes, intracellular colonization, and expression of pathogenic process encoding genes. However, information on the metabolome level is non-existent during mycoparasitism. Here, we performed a direct-infusion mass spectrometry (DIMS) metabolomics analysis using an LTQ Orbitrap analyzer in order to detect changes in the profiles of induced secondary metabolites of both partners during this mycoparasitic interaction 4 and 5 days following its establishment. The diketopiperazine(s) (DKPs) cyclo(S-Pro-S-Leu)/cyclo(S-Pro-S-Ile), ethyl 2-phenylacetate, and 3-nitro-4-hydroxybenzoic acid were detected as the primary response of Rhizoctonia 4 days following dual-culturing with Stachybotrys, whereas only the latter metabolite was up-regulated 1 day later. On the other hand, trichothecenes and atranones were mycoparasite-derived metabolites identified during mycoparasitism 4 and 5 days following dual-culturing. All the above secondary metabolites are known to exhibit bioactivity, including fungitoxicity, and represent key elements that determine the outcome of the interaction being studied. Results could be further exploited in programs for the evaluation of the bioactivity of these metabolites per se or their chemical analogs, and/or genetic engineering programs to obtain more efficient mycoparasite strains with improved efficacy and toxicological profiles. PMID:25972848

  15. Identification of a flunixin metabolite in camel by gas chromatography-mass spectrometry.

    Science.gov (United States)

    Wasfi, I A; Hadi, A A; Alkatheeri, N A; Barezaiq, I M; ElGhazali, M; Boni, N S; Zorob, O

    1998-05-29

    A flunixin metabolite, a hydroxylated product, has been identified in camel urine and plasma samples using gas chromatography-mass spectrometry (GC-MS) and GC-MS-MS in the electron impact and chemical ionization modes. Its major fragmentation pattern has been verified by GC-MS-MS in daughter ion and parent ion scan modes. The method could detect flunixin and its metabolite in camel urine after a single intravenous dose of 2.2 mg of flunixin/kg body weight for 96 and 48 h, respectively, which increases the reliability of antidoping control analysis.

  16. Identification of Ruta graveolens L. metabolites accumulated in the presence of abiotic elicitors.

    Science.gov (United States)

    Orlita, Aleksandra; Sidwa-Gorycka, Matylda; Kumirska, Jolanta; Maliński, Edmund; Siedlecka, Ewa M; Gajdus, Jerzy; Lojkowska, Ewa; Stepnowski, Piotr

    2008-01-01

    The study aimed to elucidate the effects of benzothiadiazole (BTH) and saccharin on the biosynthesis of simple coumarins, linear furanocoumarins, dihydrofuranocoumarins, and furoquinolone alkaloids in shoots of R. graveolens cultivated in vitro. The biosynthesized metabolites were analyzed and identified by GC-MS and by comparison of Kovats indices. Eight coumarin metabolites were identified: bergapten, chalepin, isopimpinelin, pinnarin, psoralen, rutacultin, rutamarin, and xanthotoxin, and also four alkaloids: dictamnine, gamma-fagarine, skimmianine, and kokusaginine. Each of the tested BTH concentrations induced a significant production of furanocoumarins and furoquinolone alkaloids. The use of saccharin also increased the production of bergapten, isopimpinelin, pinnarin, psoralen, and xanthotoxin several times.

  17. Residues of Salbutamol and Identification of Its Metabolites in Beef Cattle.

    Science.gov (United States)

    Zhang, Kai; Tang, Chaohua; Meng, Qingshi; Du, Wei; Bo, Tao; Zhao, Qingyu; Liang, Xiaowei; Liu, Shengsheng; Zhang, Zhixu; Zhang, Junmin

    2017-04-05

    Salbutamol, a selective β2-agonist, endangers the safety of animal products because of its illegal use in food animals. In this work, residues of salbutamol and its metabolites were investigated to select appropriate targets and marker residues for monitoring the illegal use of salbutamol. Ten metabolites of salbutamol were identified from plasma, urine, liver, and kidney samples; of these, six were newly identified. There were significant differences (P withdrawal time. Total salbutamol was identified as more preferable than parent salbutamol as a marker residue, and urine and eye tissues were found to be more suitable as targets for preslaughter and postslaughter monitoring of the illegal use of salbutamol in beef cattle.

  18. The simultaneous identification of metoprolol and its major acidic and basic metabolites in human urine by gas chromatography-mass spectrometry

    Energy Technology Data Exchange (ETDEWEB)

    Li, Feng; Cooper, S.F. [Universite du Quebec, Pointe-Claire (Canada)

    1996-12-31

    A novel gas chromatography-mass spectrometric (GC-MS) method was developed to confirm and identify metoprolol and its metabolites by double derivatization with S-(-)menthyl chloroformate [(-)-MCF] and N-methyl(trimethylsilyl-trifluoroacetamide) (MSTFA). This is the first report, which describes the simultaneous identification of metoprolol, its one major acidc and other basic metabolites in human urine based on solid-phase extraction with C{sub 18} reversed-phase cartridges. 12 refs., 4 figs.

  19. An Integrated Pipeline of Open Source Software Adapted for Multi-CPU Architectures: Use in the Large-Scale Identification of Single Nucleotide Polymorphisms

    Directory of Open Access Journals (Sweden)

    B. Jayashree

    2007-01-01

    Full Text Available The large amounts of EST sequence data available from a single species of an organism as well as for several species within a genus provide an easy source of identification of intra- and interspecies single nucleotide polymorphisms (SNPs. In the case of model organisms, the data available are numerous, given the degree of redundancy in the deposited EST data. There are several available bioinformatics tools that can be used to mine this data; however, using them requires a certain level of expertise: the tools have to be used sequentially with accompanying format conversion and steps like clustering and assembly of sequences become time-intensive jobs even for moderately sized datasets. We report here a pipeline of open source software extended to run on multiple CPU architectures that can be used to mine large EST datasets for SNPs and identify restriction sites for assaying the SNPs so that cost-effective CAPS assays can be developed for SNP genotyping in genetics and breeding applications. At the International Crops Research Institute for the Semi-Arid Tropics (ICRISAT, the pipeline has been implemented to run on a Paracel high-performance system consisting of four dual AMD Opteron processors running Linux with MPICH. The pipeline can be accessed through user-friendly web interfaces at http://hpc.icrisat.cgiar.org/PBSWeb and is available on request for academic use. We have validated the developed pipeline by mining chickpea ESTs for interspecies SNPs, development of CAPS assays for SNP genotyping, and confirmation of restriction digestion pattern at the sequence level.

  20. An integrated pipeline of open source software adapted for multi-CPU architectures: use in the large-scale identification of single nucleotide polymorphisms.

    Science.gov (United States)

    Jayashree, B; Hanspal, Manindra S; Srinivasan, Rajgopal; Vigneshwaran, R; Varshney, Rajeev K; Spurthi, N; Eshwar, K; Ramesh, N; Chandra, S; Hoisington, David A

    2007-01-01

    The large amounts of EST sequence data available from a single species of an organism as well as for several species within a genus provide an easy source of identification of intra- and interspecies single nucleotide polymorphisms (SNPs). In the case of model organisms, the data available are numerous, given the degree of redundancy in the deposited EST data. There are several available bioinformatics tools that can be used to mine this data; however, using them requires a certain level of expertise: the tools have to be used sequentially with accompanying format conversion and steps like clustering and assembly of sequences become time-intensive jobs even for moderately sized datasets. We report here a pipeline of open source software extended to run on multiple CPU architectures that can be used to mine large EST datasets for SNPs and identify restriction sites for assaying the SNPs so that cost-effective CAPS assays can be developed for SNP genotyping in genetics and breeding applications. At the International Crops Research Institute for the Semi-Arid Tropics (ICRISAT), the pipeline has been implemented to run on a Paracel high-performance system consisting of four dual AMD Opteron processors running Linux with MPICH. The pipeline can be accessed through user-friendly web interfaces at http://hpc.icrisat.cgiar.org/PBSWeb and is available on request for academic use. We have validated the developed pipeline by mining chickpea ESTs for interspecies SNPs, development of CAPS assays for SNP genotyping, and confirmation of restriction digestion pattern at the sequence level.

  1. Metabolite Identification Using Automated Comparison of High-Resolution Multistage Mass Spectral Trees

    NARCIS (Netherlands)

    Rojas-Cherto, M.; Peironcely, J.E.; Kasper, P.T.; Hooft, van der J.J.J.; Vos, de R.C.H.; Vreeken, R.; Hankemeier, T.; Reijmers, T.

    2012-01-01

    Multistage mass spectrometry (MSn) generating so-called spectral trees is a powerful tool in the annotation and structural elucidation of metabolites and is increasingly used in the area of accurate mass LC/MS-based metabolomics to identify unknown, but biologically relevant, compounds. As a consequ

  2. Biotransformation of the citrus flavone tangeretin in rats. Identification of metabolites with intact flavane nucleus

    DEFF Research Database (Denmark)

    Nielsen, S. E.; Breinholt, V.; Cornett, Claus;

    2000-01-01

    The present study mas carried out in order to investigate the in vivo biotransformation and excretion of the flavone, tangeretin, found in citrus fruits, by analysing urine and faeces samples from rats after repeated administration of 100 mg/kg body weight/day tangeretin. The formed metabolites w...

  3. Identification of wild chamomile species and secondary metabolites in Bushehr province

    Directory of Open Access Journals (Sweden)

    Mohammad Amin Kohanmoo

    2014-11-01

    Full Text Available Background: Chamomile is medicinal and hygienic plants which have anti -inflammatory and anti-spasmodic characteristics. Its secondary metabolites (and etc. were varied by biodiversity and environmental effect. There is little information about the wild chamomile in natural habitats of the Bushehr province. In this study, different chamomile species were selected for essential oil content and active substances. Material and methods: In this field study, several samples of chamomile from different natural habitats were collected and screened for extraction of essential oil and secondary metabolites. The essential oil and methanolic extract were prepared by water distillation liquid and flask reflux condenser stirrer, respectively these were determined by the United States and Iran pharmacopeia methods. Essential oil and methanolic extract were analyzed by GC/Mass and HPLC devices, respectively. Results: Four species, Anthemis pseudocotula, Anthemis austro-iranica, Matricaria recotita and Matricaria aurea were indicated based on screening methods. Matricaria species was observed to have essential oil and beneficiary secondary metabolites, but were not observed to be present in Anthemis species. Results of the chemical analysis showed that, Matricaria species contained Essential oil (0.6 %, Apigenin 7-Glycoside (0.62%, Chamazulen (5.5% and other substances such as derivatives of Bisabolole , Bisaboleneand Farenzene. Conclusion: Two species of wild chamomiles, Matricaria recotita and Matricaria aurea, were found in Bushehr province containing significant amount of essential oil and secondary metabolites such as Chamazulen, -αBisabolole and Apigenin. Thus these species can be cultivated for commercial proposes.

  4. Identification and quantification of metabolites of orally administered naringenin chalcone in rats.

    Science.gov (United States)

    Yoshimura, Mineka; Sano, Atsushi; Kamei, Jun-Ichi; Obata, Akio

    2009-07-22

    Naringenin chalcone is the main active component of tomato skin extract, which has an antiallergic activity. In this study, naringenin chalcone was orally administered to rats, and the chemical structures and levels of the major metabolites in the plasma and urine of rats were determined. HPLC analysis indicated the presence of three major metabolites in the urine. LC-MS and NMR analyses tentatively identified these as naringenin chalcone-2'-O-beta-D-glucuronide, naringenin-7-O-beta-D-glucuronide, and naringenin-4'-O-beta-D-glucuronide. Naringenin chalcone-2'-O-beta-D-glucuronide was the only metabolite detected in the plasma, and its peak plasma level was observed 1 h after naringenin chalcone administration. Naringenin chalcone-2'-O-beta-D-glucuronide also inhibited histamine release from rat peritoneal mast cells stimulated with compound 48/80. This activity might contribute to the antiallergic activity of naringenin chalcone in vivo. To the best of the authors' knowledge, this study is the first to report determination of naringenin chalcone metabolites in rat plasma and urine.

  5. Identification of novel metabolites from Aspergillus flavus by high resolution and multiple stage mass spectrometry.

    Science.gov (United States)

    Malysheva, Svetlana V; Arroyo-Manzanares, Natalia; Cary, Jeffrey W; Ehrlich, Kenneth C; Vanden Bussche, Julie; Vanhaecke, Lynn; Bhatnagar, Deepak; Di Mavungu, José Diana; De Saeger, Sarah

    2014-01-01

    The filamentous fungus Aspergillus flavus is one of the most important species in the Aspergillus genus and is distributed worldwide as a prevalent aflatoxin-producing food and feed contaminant. A. flavus contains more than 55 gene clusters that are predicted to encode proteins involved in secondary metabolite production. One of these, cluster 27, contains a polyketide synthase (pks27) gene that encodes a protein that is highly homologous to the aflatoxin cluster PKS. Comparative metabolomics, using ultra-high performance liquid chromatography (UHPLC) coupled to high resolution Orbitrap mass spectrometry (MS) was used to detect metabolites differentially expressed in the A. flavus wild-type and ∆pks27 mutant strains. Metabolite profiling was aided by a statistical differential analysis of MS data using SIEVE software. This differential analysis combined with accurate mass data from the Orbitrap and ion trap multiple stage MS allowed four metabolites to be identified that were produced only by the wild-type culture. These included asparasone A (358 Da), an anthraquinone pigment, and related anthraquinones with masses of 316, 340 and 374 Da. These latter three compounds had similar fragmentation patterns to that of asparasone A. The 316 Da anthraquinone is particularly interesting because it is most likely formed by incorporation of seven malonyl-CoA units rather than the eight units required for the formation of asparasone A. The 340 and 374 Da metabolites are the dehydration and an oxy-derivative of asparasone A, respectively. Asparasone A was also identified in extracts from several other Aspergillus species.

  6. Dereplication of Natural Products Using GC-TOF Mass Spectrometry: Improved Metabolite Identification by Spectral Deconvolution Ratio Analysis

    Science.gov (United States)

    Carnevale Neto, Fausto; Pilon, Alan C.; Selegato, Denise M.; Freire, Rafael T.; Gu, Haiwei; Raftery, Daniel; Lopes, Norberto P.; Castro-Gamboa, Ian

    2016-01-01

    Dereplication based on hyphenated techniques has been extensively applied in plant metabolomics, thereby avoiding re-isolation of known natural products. However, due to the complex nature of biological samples and their large concentration range, dereplication requires the use of chemometric tools to comprehensively extract information from the acquired data. In this work we developed a reliable GC-MS-based method for the identification of non-targeted plant metabolites by combining the Ratio Analysis of Mass Spectrometry deconvolution tool (RAMSY) with Automated Mass Spectral Deconvolution and Identification System software (AMDIS). Plants species from Solanaceae, Chrysobalanaceae and Euphorbiaceae were selected as model systems due to their molecular diversity, ethnopharmacological potential, and economical value. The samples were analyzed by GC-MS after methoximation and silylation reactions. Dereplication was initiated with the use of a factorial design of experiments to determine the best AMDIS configuration for each sample, considering linear retention indices and mass spectral data. A heuristic factor (CDF, compound detection factor) was developed and applied to the AMDIS results in order to decrease the false-positive rates. Despite the enhancement in deconvolution and peak identification, the empirical AMDIS method was not able to fully deconvolute all GC-peaks, leading to low MF values and/or missing metabolites. RAMSY was applied as a complementary deconvolution method to AMDIS to peaks exhibiting substantial overlap, resulting in recovery of low-intensity co-eluted ions. The results from this combination of optimized AMDIS with RAMSY attested to the ability of this approach as an improved dereplication method for complex biological samples such as plant extracts. PMID:27747213

  7. Dereplication of Natural Products Using GC-TOF Mass Spectrometry: Improved Metabolite Identification By Spectral Deconvolution Ratio Analysis

    Directory of Open Access Journals (Sweden)

    Fausto Carnevale Neto

    2016-09-01

    Full Text Available Dereplication based on hyphenated techniques has been extensively applied in plant metabolomics, avoiding re-isolation of known natural products. However, due to the complex nature of biological samples and their large concentration range, dereplication requires the use of chemometric tools to comprehensively extract information from the acquired data. In this work we developed a reliable GC-MS-based method for the identification of non-targeted plant metabolites by combining the Ratio Analysis of Mass Spectrometry deconvolution tool (RAMSY with Automated Mass Spectral Deconvolution and Identification System software (AMDIS. Plants species from Solanaceae, Chrysobalanaceae and Euphorbiaceae were selected as model systems due to their molecular diversity, ethnopharmacological potential and economical value. The samples were analyzed by GC-MS after methoximation and silylation reactions. Dereplication initiated with the use of a factorial design of experiments to determine the best AMDIS configuration for each sample, considering linear retention indices and mass spectral data. A heuristic factor (CDF, compound detection factor was developed and applied to the AMDIS results in order to decrease the false-positive rates. Despite the enhancement in deconvolution and peak identification, the empirical AMDIS method was not able to fully deconvolute all GC-peaks, leading to low MF values and/or missing metabolites. RAMSY was applied as a complementary deconvolution method to AMDIS to peaks exhibiting substantial overlap, resulting in recovery of low-intensity co-eluted ions. The results from this combination of optimized AMDIS with RAMSY attested to the ability of this approach as an improved dereplication method for complex biological samples such as plant extracts.

  8. Ultra high performance liquid chromatography-quadrupole-time of flight analysis for the identification and the determination of resveratrol and its metabolites in mouse plasma

    Energy Technology Data Exchange (ETDEWEB)

    Menet, M.C., E-mail: marie-claude.menet@parisdescartes.fr [Universite Paris Descartes, Sorbonne Paris cite, EA 4463, Faculte des Sciences Pharmaceutiques et Biologiques, 4 avenue de l' Observatoire, Paris 75270 (France); Cottart, C.H. [APHP, Groupe hospitalier Pitie-Salpetriere, Charles Foix, Service de Biochimie, 7 avenue de la Republique, Ivry sur Seine 94205 (France); Universite Paris Descartes, Sorbonne Paris cite, EA 4466, Faculte des Sciences Pharmaceutiques et Biologiques, 4 avenue de l' Observatoire, Paris 75270 (France); Taghi, M. [Universite Paris Descartes, Sorbonne Paris cite, EA 4463, Faculte des Sciences Pharmaceutiques et Biologiques, 4 avenue de l' Observatoire, Paris 75270 (France); Nivet-Antoine, V. [Universite Paris Descartes, Sorbonne Paris cite, EA 4466, Faculte des Sciences Pharmaceutiques et Biologiques, 4 avenue de l' Observatoire, Paris 75270 (France); APHP, Hopital Europeen Georges Pompidou, Service de Biochimie, 20 rue Leblanc, Paris 75015 (France); Dargere, D. [Universite Paris Descartes, Sorbonne Paris cite, EA 4463, Faculte des Sciences Pharmaceutiques et Biologiques, 4 avenue de l' Observatoire, Paris 75270 (France); and others

    2013-01-25

    Graphical abstract: Simultaneous identification and determination of new resveratrol metabolites in mice by UHPLC-Q-TOF in full scan mode. Highlights: Black-Right-Pointing-Pointer Fast method to quantify resveratrol and its main metabolites in the mouse plasma. Black-Right-Pointing-Pointer Isotope-labeled standards to build a linear calibration curve. Black-Right-Pointing-Pointer Linear calibration curve on a wide range of concentrations. Black-Right-Pointing-Pointer Simultaneous identification and quantification of metabolites by using full scan mode. Black-Right-Pointing-Pointer Detection of uncommon metabolites not yet described in mice. - Abstract: Resveratrol is a polyphenol that has numerous interesting biological properties, but, per os, it is quickly metabolized. Some of its metabolites are more concentrated than resveratrol, may have greater biological activities, and may act as a kind of store for resveratrol. Thus, to understand the biological impact of resveratrol on a physiological system, it is crucial to simultaneously analyze resveratrol and its metabolites in plasma. This study presents an analytical method based on UHPLC-Q-TOF mass spectrometry for the quantification of resveratrol and of its most common hydrophilic metabolites. The use of {sup 13}C- and D-labeled standards specific to each molecule led to a linear calibration curve on a larger concentration range than described previously. The use of high resolution mass spectrometry in the full scan mode enabled simultaneous identification and quantification of some hydrophilic metabolites not previously described in mice. In addition, UHPLC separation, allowing run times lower than 10 min, can be used in studies that requiring analysis of many samples.

  9. Subpathway-CorSP: Identification of metabolic subpathways via integrating expression correlations and topological features between metabolites and genes of interest within pathways.

    Science.gov (United States)

    Feng, Chenchen; Zhang, Jian; Li, Xuecang; Ai, Bo; Han, Junwei; Wang, Qiuyu; Wei, Taiming; Xu, Yong; Li, Meng; Li, Shang; Song, Chao; Li, Chunquan

    2016-09-14

    Metabolic pathway analysis is a popular strategy for comprehensively researching metabolites and genes of interest associated with specific diseases. However, the traditional pathway identification methods do not accurately consider the combined effect of these interesting molecules and neglects expression correlations or topological features embedded in the pathways. In this study, we propose a powerful method, Subpathway-CorSP, for identifying metabolic subpathway regions. This method improved on original pathway identification methods by using a subpathway identification strategy and emphasizing expression correlations between metabolites and genes of interest based on topological features within the metabolic pathways. We analyzed a prostate cancer data set and its metastatic sub-group data set with detailed comparison of Subpathway-CorSP with four traditional pathway identification methods. Subpathway-CorSP was able to identify multiple subpathway regions whose entire corresponding pathways were not detected by traditional pathway identification methods. Further evidences indicated that Subpathway-CorSP provided a robust and efficient way of reliably recalling cancer-related subpathways and locating novel subpathways by the combined effect of metabolites and genes. This was a novel subpathway strategy based on systematically considering expression correlations and topological features between metabolites and genes of interest within given pathways.

  10. Identification and validation of urinary metabolite biomarkers for major depressive disorder.

    Science.gov (United States)

    Zheng, Peng; Wang, Ying; Chen, Liang; Yang, Deyu; Meng, Huaqing; Zhou, Dezhi; Zhong, Jiaju; Lei, Yang; Melgiri, N D; Xie, Peng

    2013-01-01

    Major depressive disorder (MDD) is a widespread and debilitating mental disorder. However, there are no biomarkers available to aid in the diagnosis of this disorder. In this study, a nuclear magnetic resonance spectroscopy-based metabonomic approach was employed to profile urine samples from 82 first-episode drug-naïve depressed subjects and 82 healthy controls (the training set) in order to identify urinary metabolite biomarkers for MDD. Then, 44 unselected depressed subjects and 52 healthy controls (the test set) were used to independently validate the diagnostic generalizability of these biomarkers. A panel of five urinary metabolite biomarkers-malonate, formate, N-methylnicotinamide, m-hydroxyphenylacetate, and alanine-was identified. This panel was capable of distinguishing depressed subjects from healthy controls with an area under the receiver operating characteristic curve (AUC) of 0.81 in the training set. Moreover, this panel could classify blinded samples from the test set with an AUC of 0.89. These findings demonstrate that this urinary metabolite biomarker panel can aid in the future development of a urine-based diagnostic test for MDD.

  11. Identification of metabolites, clinical chemistry markers and transcripts associated with hepatotoxicity.

    Directory of Open Access Journals (Sweden)

    Andreas Buness

    Full Text Available Early and accurate pre-clinical and clinical biomarkers of hepatotoxicity facilitate the drug development process and the safety monitoring in clinical studies. We selected eight known model compounds to be administered to male Wistar rats to identify biomarkers of drug induced liver injury (DILI using transcriptomics, metabolite profiling (metabolomics and conventional endpoints. We specifically explored early biomarkers in serum and liver tissue associated with histopathologically evident acute hepatotoxicity. A tailored data analysis strategy was implemented to better differentiate animals with no treatment-related findings in the liver from animals showing evident hepatotoxicity as assessed by histopathological analysis. From the large number of assessed parameters, our data analysis strategy allowed us to identify five metabolites in serum and five in liver tissue, 58 transcripts in liver tissue and seven clinical chemistry markers in serum that were significantly associated with acute hepatotoxicity. The identified markers comprised metabolites such as taurocholic acid and putrescine (measured as sum parameter together with agmatine, classical clinical chemistry markers like AST (aspartate aminotransferase, ALT (alanine aminotransferase, and bilirubin, as well as gene transcripts like Igfbp1 (insulin-like growth factor-binding protein 1 and Egr1 (early growth response protein 1. The response pattern of the identified biomarkers was concordant across all types of parameters and sample matrices. Our results suggest that a combination of several of these biomarkers could significantly improve the robustness and accuracy of an early diagnosis of hepatotoxicity.

  12. Phylogenetic Identification of Fungi Isolated from the Marine Sponge Tethya aurantium and Identification of Their Secondary Metabolites

    Directory of Open Access Journals (Sweden)

    Jutta Wiese

    2011-04-01

    Full Text Available Fungi associated with the marine sponge Tethya aurantium were isolated and identified by morphological criteria and phylogenetic analyses based on internal transcribed spacer (ITS regions. They were evaluated with regard to their secondary metabolite profiles. Among the 81 isolates which were characterized, members of 21 genera were identified. Some genera like Acremonium, Aspergillus, Fusarium, Penicillium, Phoma, and Trichoderma are quite common, but we also isolated strains belonging to genera like Botryosphaeria, Epicoccum, Parasphaeosphaeria, and Tritirachium which have rarely been reported from sponges. Members affiliated to the genera Bartalinia and Volutella as well as to a presumably new Phoma species were first isolated from a sponge in this study. On the basis of their classification, strains were selected for analysis of their ability to produce natural products. In addition to a number of known compounds, several new natural products were identified. The scopularides and sorbifuranones have been described elsewhere. We have isolated four additional substances which have not been described so far. The new metabolite cillifuranone (1 was isolated from Penicillium chrysogenum strain LF066. The structure of cillifuranone (1 was elucidated based on 1D and 2D NMR analysis and turned out to be a previously postulated intermediate in sorbifuranone biosynthesis. Only minor antibiotic bioactivities of this compound were found so far.

  13. Leadership Pipeline

    DEFF Research Database (Denmark)

    Elmholdt, Claus Westergård

    2012-01-01

    Artiklen analyserer grundlaget for Leadership Pipeline modellen med henblik på en vurdering af substansen bag modellen, og perspektiverne for generalisering af modellen til en dansk organisatorisk kontekst.......Artiklen analyserer grundlaget for Leadership Pipeline modellen med henblik på en vurdering af substansen bag modellen, og perspektiverne for generalisering af modellen til en dansk organisatorisk kontekst....

  14. CYP450 phenotyping and accurate mass identification of metabolites of the 8-aminoquinoline, anti-malarial drug primaquine

    Directory of Open Access Journals (Sweden)

    Pybus Brandon S

    2012-08-01

    Full Text Available Abstract Background The 8-aminoquinoline (8AQ drug primaquine (PQ is currently the only approved drug effective against the persistent liver stage of the hypnozoite forming strains Plasmodium vivax and Plasmodium ovale as well as Stage V gametocytes of Plasmodium falciparum. To date, several groups have investigated the toxicity observed in the 8AQ class, however, exact mechanisms and/or metabolic species responsible for PQ’s haemotoxic and anti-malarial properties are not fully understood. Methods In the present study, the metabolism of PQ was evaluated using in vitro recombinant metabolic enzymes from the cytochrome P450 (CYP and mono-amine oxidase (MAO families. Based on this information, metabolite identification experiments were performed using nominal and accurate mass measurements. Results Relative activity factor (RAF-weighted intrinsic clearance values show the relative role of each enzyme to be MAO-A, 2C19, 3A4, and 2D6, with 76.1, 17.0, 5.2, and 1.7% contributions to PQ metabolism, respectively. CYP 2D6 was shown to produce at least six different oxidative metabolites along with demethylations, while MAO-A products derived from the PQ aldehyde, a pre-cursor to carboxy PQ. CYPs 2C19 and 3A4 produced only trace levels of hydroxylated species. Conclusions As a result of this work, CYP 2D6 and MAO-A have been implicated as the key enzymes associated with PQ metabolism, and metabolites previously identified as potentially playing a role in efficacy and haemolytic toxicity have been attributed to production via CYP 2D6 mediated pathways.

  15. Krebs cycle metabolite profiling for identification and stratification of pheochromocytomas/paragangliomas due to succinate dehydrogenase deficiency.

    Science.gov (United States)

    Richter, Susan; Peitzsch, Mirko; Rapizzi, Elena; Lenders, Jacques W; Qin, Nan; de Cubas, Aguirre A; Schiavi, Francesca; Rao, Jyotsna U; Beuschlein, Felix; Quinkler, Marcus; Timmers, Henri J; Opocher, Giuseppe; Mannelli, Massimo; Pacak, Karel; Robledo, Mercedes; Eisenhofer, Graeme

    2014-10-01

    Mutations of succinate dehydrogenase A/B/C/D genes (SDHx) increase susceptibility to development of pheochromocytomas and paragangliomas (PPGLs), with particularly high rates of malignancy associated with SDHB mutations. We assessed whether altered succinate dehydrogenase product-precursor relationships, manifested by differences in tumor ratios of succinate to fumarate or other metabolites, might aid in identifying and stratifying patients with SDHx mutations. PPGL tumor specimens from 233 patients, including 45 with SDHx mutations, were provided from eight tertiary referral centers for mass spectrometric analyses of Krebs cycle metabolites. Diagnostic performance of the succinate:fumarate ratio for identification of pathogenic SDHx mutations. SDH-deficient PPGLs were characterized by 25-fold higher succinate and 80% lower fumarate, cis-aconitate, and isocitrate tissue levels than PPGLs without SDHx mutations. Receiver-operating characteristic curves for use of ratios of succinate to fumarate or to cis-aconitate and isocitrate to identify SDHx mutations indicated areas under curves of 0.94 to 0.96; an optimal cut-off of 97.7 for the succinate:fumarate ratio provided a diagnostic sensitivity of 93% at a specificity of 97% to identify SDHX-mutated PPGLs. Succinate:fumarate ratios were higher in both SDHB-mutated and metastatic tumors than in those due to SDHD/C mutations or without metastases. Mass spectrometric-based measurements of ratios of succinate:fumarate and other metabolites in PPGLs offer a useful method to identify patients for testing of SDHx mutations, with additional utility to quantitatively assess functionality of mutations and metabolic factors responsible for malignant risk.

  16. Identification of combined conjugation of nabumetone phase I metabolites with glucuronic acid and glycine in minipig biotransformation using coupling high-performance liquid chromatography with electrospray ionization mass spectrometry.

    Science.gov (United States)

    Česlová, Lenka; Holčapek, Michal; Nobilis, Milan

    2014-01-01

    High-performance liquid chromatography (HPLC) coupled with electrospray ionization mass spectrometry (ESI-MS) was applied for the analysis of nabumetone metabolites during the biotransformation in minipigs. In addition to known phase I metabolites, the identification of phase II metabolites was achieved on the basis of their full-scan mass spectra and subsequent MS(n) analysis using both positive-ion and negative-ion ESI mode. Some phase I metabolites are conjugated with both glucuronide acid and glycine, which is quite unusual type of phase II metabolite not presented so far for nabumetone. These metabolites were found in small intestine content, but they were absent in minipigs urine.

  17. Target identification of volatile metabolites to allow the differentiation of lactic acid bacteria by gas chromatography-ion mobility spectrometry.

    Science.gov (United States)

    Gallegos, Janneth; Arce, Cristina; Jordano, Rafael; Arce, Lourdes; Medina, Luis M

    2017-04-01

    The purpose of this work was to study the potential of gas chromatography-ion mobility spectrometry (GC-IMS) to differentiate lactic acid bacteria (LAB) through target identification and fingerprints of volatile metabolites. The LAB selected were used as reference strains for their influence in the flavour of cheese. The four strains of LAB can be distinguished by the fingerprints generated by the volatile organic compounds (VOCs) emitted. 2-butanone, 2-pentanone, 2-heptanone and 3-methyl-1-butanol were identified as relevant VOCs for Lactobacillus casei and Lactobacillus paracasei subsp. paracasei. 2-Butanone and 3-methyl-1-butanol were identified in Lactococcus lactis subsp. lactis and Lactococcus cremoris subsp. cremoris. The IMS signals monitoring during a 24-30h period showed the growth of the LAB in vitro. The results demonstrated that GC-IMS is a useful technology for bacteria recognition and also for screening the aromatic potential of new isolates of LAB.

  18. Identification and quantification of metabolites of the fungicide tebuconazole in human urine.

    Science.gov (United States)

    Mercadante, R; Polledri, E; Scurati, S; Moretto, A; Fustinoni, S

    2014-11-17

    Tebuconazole (TEB) is a fungicide used in agriculture; the objective of this work was to identify and quantify TEB metabolites in human urine. Samples from seven vineyard workers exposed to TEB were submitted to liquid chromatography interfaced with a triple quadrupole mass spectrometer, equipped with an electron spray source, and a linear ion trap to gain a profile of candidate metabolites. Based on the presence of the ion m/z 70 in the MS/MS spectra, which corresponds to protonated triazole (a specific moiety of TEB), and the isotopic pattern of the molecular ions, typical of molecules with one chlorine atom, hydroxyl and carboxyl derivatives of TEB, that is, TEB-OH and TEB-COOH, were identified as major metabolites, both as free molecules and as glucuronide (Glc) conjugates. The mean molar fractions were 0.67, 0.13, 0.13, and 0.07 for TEB-O-Glc, TEB-OH, TEB-COO-Glc, and TEB-COOH. Urine samples were submitted to hydrolysis with β-glucuronidase, and the free compounds were quantified in the presence of deuterated TEB (TEB-d6) as the internal standard (IS), by multiple reaction monitoring (MRM) mode. The assay was linear in the ranges of 0.2-600 μg/L and 0.1-240 μg/L for TEB-OH and TEB-COOH, respectively; precision, accuracy, and the limit of quantification (LOQ) were <3.1%, 98-103%, and 0.3 μg/L for both analytes. An evaluation of matrix effects showed that the use of TEB-d6 controlled these sources of bias. The urinary levels of TEB-OH and TEB-COOH in specimens collected from farmers exposed to TEB ranged from 10 to 473 and from 3 to 159 μg/L, respectively.

  19. The identification of lobeglitazone metabolites in rat liver microsomes and the kinetics of the in vivo formation of the major metabolite M1 in rats.

    Science.gov (United States)

    Lee, Jong-Hwa; Ahn, Sung Hoon; Maeng, Han-Joo; Lee, Wooin; Kim, Dae-Duk; Chung, Suk-Jae

    2015-11-10

    The objective of this study was to elucidate the chemical structure of the metabolites derived from lobeglitazone (LB) during its incubation with rat liver microsomes and to characterize the kinetics of formation of the major metabolite M1 in vivo. Using high performance liquid chromatography coupled with a hybrid quadrupole linear ion trap, the metabolites were derived from LB during its incubation with rat liver microsomes. From various fragmentation patterns obtained from the metabolites, LB was biotransformed into 5 metabolites in the incubation, in which demethylation and hydroxylation appeared to be the principle metabolic pathways in vitro; Amongst the five primary metabolites, M1, a demethylated derivative of LB, appeared to be the major metabolite of LB, based on a comparison on the peak intensities in the ion chromatogram. In a study of the in vivo kinetics of formation of M1 in rats, the rate of formation of M1 from LB was determined to be 0.252 and 0.216mL/min/kg at doses of 0.5mg/kg and 2mg/kg of LB, respectively, suggesting that the kinetics of M1 formation were linear in the dose range tested. Considering the fact that LB is primarily eliminated by hepatic metabolism in rats, the formation of M1 accounts for approximately 7.50-9.76% of the overall elimination of LB in rats.

  20. Definitive Metabolite Identification Coupled with Automated Ligand Identification System (ALIS) Technology: A Novel Approach to Uncover Structure-Activity Relationships and Guide Drug Design in a Factor IXa Inhibitor Program.

    Science.gov (United States)

    Zhang, Ting; Liu, Yong; Yang, Xianshu; Martin, Gary E; Yao, Huifang; Shang, Jackie; Bugianesi, Randal M; Ellsworth, Kenneth P; Sonatore, Lisa M; Nizner, Peter; Sherer, Edward C; Hill, Susan E; Knemeyer, Ian W; Geissler, Wayne M; Dandliker, Peter J; Helmy, Roy; Wood, Harold B

    2016-03-10

    A potent and selective Factor IXa (FIXa) inhibitor was subjected to a series of liver microsomal incubations, which generated a number of metabolites. Using automated ligand identification system-affinity selection (ALIS-AS) methodology, metabolites in the incubation mixture were prioritized by their binding affinities to the FIXa protein. Microgram quantities of the metabolites of interest were then isolated through microisolation analytical capabilities, and structurally characterized using MicroCryoProbe heteronuclear 2D NMR techniques. The isolated metabolites recovered from the NMR experiments were then submitted directly to an in vitro FIXa enzymatic assay. The order of the metabolites' binding affinity to the Factor IXa protein from the ALIS assay was completely consistent with the enzymatic assay results. This work showcases an innovative and efficient approach to uncover structure-activity relationships (SARs) and guide drug design via microisolation-structural characterization and ALIS capabilities.

  1. Identification of glutathione and related cysteine conjugates derived from reactive metabolites of methyleugenol in rats.

    Science.gov (United States)

    Yao, Huina; Peng, Ying; Zheng, Jiang

    2016-06-25

    Methyleugenol (ME), an alkenylbenzene compound, is a constituent of many foods and is used as flavoring agent in foodstuffs and as fragrance in cosmetics. It has been reported that exposure to ME can cause carcinogenicity, cytotoxicity, and genotoxicity. Metabolic activation is suggested to play an important role in ME-induced toxicities. Electrophilic metabolites of ME have been reported to covalently bind to proteins and nucleic acids. The objective of this study was to identify GSH and related cysteine conjugates derived from these reactive metabolites in vivo. Five biliary GSH (M1-M5) and four urinary cysteine conjugates (M6-M9) were detected in rats given ME. M1 and M2 were GSH conjugates derived from the epoxide of ME. M3, M4, and M5 were GSH conjugates possibly generated from the corresponding α,β-unsaturated aldehyde, carbonium ion, and quinone methide, respectively. The structures of the GSH conjugates were verified by chemical synthesis. Cysteine conjugates M6, M7, M8, and M9 were found to correspond to the respective M1/M2, M3, M4, and M5. The data obtained from the present in vivo work facilitate the understanding of mechanism action of ME toxicities and may provide information suitable for use as biomarkers of exposure to ME.

  2. Identification of a novel human deoxynivalenol metabolite enhancing proliferation of intestinal and urinary bladder cells

    Science.gov (United States)

    Warth, Benedikt; Del Favero, Giorgia; Wiesenberger, Gerlinde; Puntscher, Hannes; Woelflingseder, Lydia; Fruhmann, Philipp; Sarkanj, Bojan; Krska, Rudolf; Schuhmacher, Rainer; Adam, Gerhard; Marko, Doris

    2016-09-01

    The mycotoxin deoxynivalenol (DON) is an abundant contaminant of cereal based food and a severe issue for global food safety. We report the discovery of DON-3-sulfate as a novel human metabolite and potential new biomarker of DON exposure. The conjugate was detectable in 70% of urine samples obtained from pregnant women in Croatia. For the measurement of urinary metabolites, a highly sensitive and selective LC-MS/MS method was developed and validated. The method was also used to investigate samples from a duplicate diet survey for studying the toxicokinetics of DON-3-sulfate. To get a preliminary insight into the biological relevance of the newly discovered DON-sulfates, in vitroexperiments were performed. In contrast to DON, sulfate conjugates lacked potency to suppress protein translation. However, surprisingly we found that DON-sulfates enhanced proliferation of human HT-29 colon carcinoma cells, primary human colon epithelial cells (HCEC-1CT) and, to some extent, also T24 bladder cancer cells. A proliferative stimulus, especially in tumorigenic cells raises concern on the potential impact of DON-sulfates on consumer health. Thus, a further characterization of their toxicological relevance should be of high priority.

  3. Pharmacologically active metabolites, combination screening and target identification-driven drug repositioning in antituberculosis drug discovery.

    Science.gov (United States)

    Kigondu, Elizabeth M; Wasuna, Antonina; Warner, Digby F; Chibale, Kelly

    2014-08-15

    There has been renewed interest in alternative strategies to address bottlenecks in antibiotic development. These include the repurposing of approved drugs for use as novel anti-infective agents, or their exploitation as leads in drug repositioning. Such approaches are especially attractive for tuberculosis (TB), a disease which remains a leading cause of morbidity and mortality globally and, increasingly, is associated with the emergence of drug-resistance. In this review article, we introduce a refinement of traditional drug repositioning and repurposing strategies involving the development of drugs that are based on the active metabolite(s) of parental compounds with demonstrated efficacy. In addition, we describe an approach to repositioning the natural product antibiotic, fusidic acid, for use against Mycobacterium tuberculosis. Finally, we consider the potential to exploit the chemical matter arising from these activities in combination screens and permeation assays which are designed to confirm mechanism of action (MoA), elucidate potential synergies in polypharmacy, and to develop rules for drug permeability in an organism that poses a special challenge to new drug development. Copyright © 2014 Elsevier Ltd. All rights reserved.

  4. Identification of a novel human deoxynivalenol metabolite enhancing proliferation of intestinal and urinary bladder cells

    Science.gov (United States)

    Warth, Benedikt; Del Favero, Giorgia; Wiesenberger, Gerlinde; Puntscher, Hannes; Woelflingseder, Lydia; Fruhmann, Philipp; Sarkanj, Bojan; Krska, Rudolf; Schuhmacher, Rainer; Adam, Gerhard; Marko, Doris

    2016-01-01

    The mycotoxin deoxynivalenol (DON) is an abundant contaminant of cereal based food and a severe issue for global food safety. We report the discovery of DON-3-sulfate as a novel human metabolite and potential new biomarker of DON exposure. The conjugate was detectable in 70% of urine samples obtained from pregnant women in Croatia. For the measurement of urinary metabolites, a highly sensitive and selective LC-MS/MS method was developed and validated. The method was also used to investigate samples from a duplicate diet survey for studying the toxicokinetics of DON-3-sulfate. To get a preliminary insight into the biological relevance of the newly discovered DON-sulfates, in vitroexperiments were performed. In contrast to DON, sulfate conjugates lacked potency to suppress protein translation. However, surprisingly we found that DON-sulfates enhanced proliferation of human HT-29 colon carcinoma cells, primary human colon epithelial cells (HCEC-1CT) and, to some extent, also T24 bladder cancer cells. A proliferative stimulus, especially in tumorigenic cells raises concern on the potential impact of DON-sulfates on consumer health. Thus, a further characterization of their toxicological relevance should be of high priority. PMID:27659167

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

    Directory of Open Access Journals (Sweden)

    Miranda Y Fong

    Full Text Available 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, p<0.001; 1.88 fold in MOC, p<0.001, acetylcarnitine (1.75 fold in EOC, p<0.001; 2.39 fold in MOC, p<0.001, and butyrylcarnitine (3.62 fold, p<0.0094 in EOC; 7.88 fold, p<0.001 in MOC. There were also significant changes in phenylalanine catabolism marked by increases in phenylpyruvate (4.21 fold; p = 0.0098 and phenyllactate (195.45 fold; p<0.0023 in EOC. Ovarian cancer 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, p<0.001 and several isoforms of tocopherols. We have also identified novel metabolites in the ovary, 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.

  6. Comparison of trapping profiles between d-peptides and glutathione in the identification of reactive metabolites

    Directory of Open Access Journals (Sweden)

    Jaana E. Laine

    2015-01-01

    Full Text Available Qualitative trapping profile of reactive metabolites arising from six structurally different compounds was tested with three different d-peptide isomers (Peptide 1, gly–tyr–pro–cys–pro–his-pro; Peptide 2, gly–tyr–pro–ala–pro–his–pro; Peptide 3, gly–tyr–arg–pro–cys–pro–his–lys–pro and glutathione (GSH using mouse and human liver microsomes as the biocatalyst. The test compounds were classified either as clinically “safe” (amlodipine, caffeine, ibuprofen, or clinically as “risky” (clozapine, nimesulide, ticlopidine; i.e., associated with severe clinical toxicity outcomes. Our working hypothesis was as follows: could the use of short different amino acid sequence containing d-peptides in adduct detection confer any add-on value to that obtained with GSH? All “risky” agents’ resulted in the formation of several GSH adducts in the incubation mixture and with at least one peptide adduct with both microsomal preparations. Amlodipine did not form any adducts with any of the trapping agents. No GSH and peptide 2 and 3 adducts were found with caffeine, but with peptide 1 one adduct with human liver microsomes was detected. Ibuprofen produced one Peptide 1-adduct with human and mouse liver microsomes but not with GSH. In conclusion, GSH still remains the gold trapping standard for reactive metabolites. However, targeted d-peptides could provide additional information about protein binding potential of electrophilic agents, but their clinical significance needs to be clarified using a wider spectrum of chemicals together with other safety estimates.

  7. The application of a new microfluidic device for the simultaneous identification and quantitation of midazolam metabolites obtained from a single micro-litre of chimeric mice blood.

    Science.gov (United States)

    Gallagher, Richard; Dillon, Leonard; Grimsley, Aidan; Murphy, Jim; Samuelsson, Kristin; Douce, David

    2014-06-15

    Improvements in the design of low-flow highly sensitive chromatographic ion source interfaces allow the detection and characterisation of drugs and metabolites from smaller sample volumes. This in turn improves the ethical treatment of animals by reducing both the number of animals needed and the blood sampling volumes required. A new microfluidic device combining an ultra-high pressure liquid chromatography (UHPLC) analytical column with a nano-flow electrospray source is described. All microfluidic, gas and electrical connections are automatically engaged when the ceramic microfluidic device is inserted into the source enclosure. The system was used in conjunction with a hybrid quadrupole-time-of-flight mass spectrometer. The improved sensitivity of the system is highlighted in its application in the quantification and qualification of midazolam and its metabolites detected in whole blood from chimeric and wild-type mice. Metabolite identification and full pharmacokinetic profiles were obtained from a single micro-litre of whole blood at each sampling time and significant pharmacokinetic differences were observed between the two types of mice. Improvements in the enhanced ionisation efficiency from the microfluidic device in conjunction with nanoUHPLC/MS was sufficiently sensitive for the identification and quantification of midazolam metabolites from a single micro-litre of whole blood. Detection of metabolites not previously recorded from the chimeric mouse in vivo model was made. Copyright © 2014 John Wiley & Sons, Ltd.

  8. Liquid Chromatography/Quadrupole Time-of-Flight Mass Spectrometry for Identification of In Vitro and In Vivo Metabolites of Bornyl Gallate in Rats

    Directory of Open Access Journals (Sweden)

    Wei Lan

    2013-01-01

    Full Text Available Bornyl gallate (BG is a potential drug candidate synthesized by the reaction of two natural products, gallic acid and borneol. Previous studies have strongly suggested that BG is worthy of further investigation due to antioxidant, antiatherosclerosis activities, and obvious activity of stimulating intersegmental vessel growth in zebrafish. This work was designed to elucidate the metabolic profile of BG through analyzing its metabolites in vitro and in vivo by a chromatographic separation coupled with a mass spectrometry. The metabolites of BG were characterized from the rat liver microsome incubation solution, as well as rat urine and plasma after oral administration. Chromatographic separation was performed on an Agilent TC-C18 column (250 mm × 4.6 mm, 5 μm with gradient elution using methanol and water containing 0.2% (V : V formic acid as the mobile phase. Metabolites identification involved analyzing the retention behaviors, changes of molecular weights and MS/MS fragment patterns of BG and the metabolites. Five compounds were identified as isomers of hydroxylated BG metabolites in vitro. The major metabolites of BG in rat urine and plasma proved to be BG-O-glucuronide and O-methyl BG-O-glucuronide. The proposed method confirmed to be a reliable and sensitive alternative for characterizing metabolic pathways of BG.

  9. Proposal of 5-methoxy-N-methyl-N-isopropyltryptamine consumption biomarkers through identification of in vivo metabolites from mice.

    Science.gov (United States)

    Fabregat-Safont, D; Barneo-Muñoz, M; Martinez-Garcia, F; Sancho, J V; Hernández, F; Ibáñez, M

    2017-07-28

    New psychoactive substances (NPS) are a new breed of synthetically produced substances designed to mimic the effects of traditional illegal drugs. Synthetic cannabinoids and synthetic cathinones are the two most common groups, which try to mimic the effects of the natural compounds (9)Δ-tetrahydrocannabinol and cathinone, respectively. Similarly, synthetic tryptamines are designer compounds which are based on the compounds psilocin, N,N-dimethyltryptamine and 5-methoxy-N,N-dimethyltryptamine found in some mushrooms. One of the most important tryptamine compounds found in seizures is 5-methoxy-N,N-diisopropyltryptamine, which has been placed as controlled substance in USA and some European countries. The control of this compound has promoted the rising of another tryptamine, the 5-methoxy-N-methyl-N-isopropyltryptamine, which at the time of writing this article has not been banned yet. So, it is undeniable that this new substance should be monitored. 5-methoxy-N-methyl-N-isopropyltryptamine has been reported by the Spanish Early Warning System and detected in our laboratory in two pill samples purchased in a local smart shop. This has promoted the need of stablishing consumption markers for this compound in consumers' urine. In the present work, the metabolism and pharmacokinetic of 5-methoxy-N-methyl-N-isopropyltryptamine has been studied by an in vivo approach, using adult male mice of the inbred strain C57BLJ/6. The use of ultra-high performance liquid chromatography coupled to high resolution mass spectrometry allowed the identification of four metabolites. After the pharmacokinetic study in serum and urine, the O-demethylated metabolite and the non-metabolised parent compound are proposed as consumption markers in hydrolysed urine. Data reported in this work will help hospitals and forensic laboratories to monitor the consumption and potential intoxication cases related to this tryptamine. Copyright © 2017 Elsevier B.V. All rights reserved.

  10. Identification of a new metabolite of GHB: gamma-hydroxybutyric acid glucuronide.

    Science.gov (United States)

    Petersen, Ida Nymann; Tortzen, Christian; Kristensen, Jesper Langgaard; Pedersen, Daniel Sejer; Breindahl, Torben

    2013-06-01

    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-GLUC and a deuterated analogue for chromatography were synthesized. Liquid chromatography and tandem mass spectrometry were used for targeted analysis in anonymous clinical urine samples (n = 50). GHB-GLUC was found in concentrations ranging from 0.11 to 5.0 µg/mL (mean: 1.3 ± 1.2 µg/mL). Thus far, this is the first report of a GHB glucuronide detected in biological samples. Given that glucuronides generally have longer half-life values than their corresponding free drugs, GHB-GLUC should theoretically be a biomarker of GHB intoxication. It is also proposed that the hitherto unexplained reports of elevated GHB concentrations in some biological samples, which has caused the setting of a relatively high cutoff value (10 µg/mL), represent total GHB measurements (sum of free GHB and actively chemically hydrolyzed GHB-GLUC). To address these challenges, the present study must be followed by comprehensive pharmacokinetic and stability studies after the controlled administration of GHB.

  11. Identification and analysis of metabolite production with biotechnological potential in Xanthophyllomyces dendrorhous isolates.

    Science.gov (United States)

    Contreras, Gabriela; Barahona, Salvador; Sepúlveda, Dionisia; Baeza, Marcelo; Cifuentes, Víctor; Alcaíno, Jennifer

    2015-03-01

    Antarctic microorganisms have developed different strategies to live in their environments, including modifications to their membrane components to regulate fluidity and the production of photoprotective metabolites such as carotenoids. Three yeast colonies (ANCH01, ANCH06 and ANCH08) were isolated from soil samples collected at King George Island, which according to their rDNA sequence analyses, were determined to be Xanthophyllomyces dendrorhous. This yeast is of biotechnological interest, because it can synthesize astaxanthin as its main carotenoid, which is a powerful antioxidant pigment used in aquaculture. Then, the aim of this work was to characterize the ANCH isolates at their molecular and phenotypic level. The isolates did not display any differences in their rDNA and COX1 gene nucleotide sequences. However, ANCH01 produces approximately sixfold more astaxanthin than other wild type strains. Moreover, even though ANCH06 and ANCH08 produce astaxanthin, their main carotenoid was β-carotene. In contrast to other X. dendrorhous strains, the ANCH isolates did not produce mycosporines. Finally, the ANCH isolates had a higher proportion of polyunsaturated fatty acids than other wild type strains. In conclusion, the reported X. dendrorhous isolates are phenotypically different from other wild type strains, including characteristics that could make them more resistant and better able to inhabit their original habitat, which may also have biotechnological potential.

  12. HPLC-DAD-MS identification of bioactive secondary metabolites from Ferula communis roots.

    Science.gov (United States)

    Arnoldi, Lolita; Ballero, Mauro; Fuzzati, Nicola; Maxia, Andrea; Mercalli, Enrico; Pagni, Luca

    2004-06-01

    A simple HPLC method was developed to distinguish between 'poisonous' and 'non-poisonous' chemotypes of Ferula communis. The method was performed on a C8 reverse phase analytical column using a binary eluent (aqueous TFA 0.01%-TFA 0.01% in acetonitrile) under gradient condition. The two chemotypes showed different fingerprints. The identification of five coumarins and eleven daucane derivatives by HPLC-diode array detection (HPLC-DAD) and HPLC-MS is described. A coumarin, not yet described, was detected.

  13. 1H NMR metabolite fingerprinting as a new tool for body fluid identification in forensic science.

    Science.gov (United States)

    Scano, Paola; Locci, Emanuela; Noto, Antonio; Navarra, Gabriele; Murgia, Federica; Lussu, Milena; Barberini, Luigi; Atzori, Luigi; De Giorgio, Fabio; Rosa, Maria Francesca; d'Aloja, Ernesto

    2013-08-01

    In this feasibility study, we propose, for the first time, (1)H NMR spectroscopy coupled with mathematical strategies as a valid tool for body fluid (BF) trace identification in forensic science. In order to assess the ability of this approach to identify traces composed either by a single or by two different BFs, samples of blood, urine, saliva, and semen were collected from different donors, and binary mixtures were prepared. (1)H NMR analyses were carried out for all samples. Spectral data of the whole set were firstly submitted to unsupervised principal component analysis (PCA); it showed that samples of the same BF cluster well on the basis of their characterizing molecular components and that mixtures exhibit intermediate characteristics among BF typologies. Furthermore, samples were divided into a training set and a test set. An average NMR spectral profile for each typology of BF was obtained from the training set and validated as representative of each BF class. Finally, a fitting procedure, based on a system of linear equations with the four obtained average spectral profiles, was applied to the test set and the mixture samples; it showed that BFs can be unambiguously identified, even as components of a mixture. The successful use of this mathematical procedure has the advantage, in forensics, of overcoming bias due to the analyst's personal judgment. We therefore propose this combined approach as a valid, fast, and non-destructive tool for addressing the challenges in the identification of composite traces in forensics.

  14. Leadership Pipeline

    DEFF Research Database (Denmark)

    Elmholdt, Claus Westergård

    2013-01-01

    I artiklen undersøges det empiriske grundlag for Leader- ship Pipeline. Først beskrives Leadership Pipeline modellen om le- delsesbaner og skilleveje i opadgående transitioner mellem orga- nisatoriske ledelsesniveauer (Freedman, 1998; Charan, Drotter and Noel, 2001). Dernæst sættes fokus på det...... forholdet mellem kontinuitet- og diskontinuitet i ledel- seskompetencer på tværs af organisatoriske niveauer præsenteres og diskuteres. Afslutningsvis diskuteres begrænsningerne i en kompetencebaseret tilgang til Leadership Pipeline, og det foreslås, at succesfuld ledelse i ligeså høj grad afhænger af...

  15. Leadership Pipeline

    DEFF Research Database (Denmark)

    Elmholdt, Claus Westergård

    2013-01-01

    I artiklen undersøges det empiriske grundlag for Leader- ship Pipeline. Først beskrives Leadership Pipeline modellen om le- delsesbaner og skilleveje i opadgående transitioner mellem orga- nisatoriske ledelsesniveauer (Freedman, 1998; Charan, Drotter and Noel, 2001). Dernæst sættes fokus på det...... forholdet mellem kontinuitet- og diskontinuitet i ledel- seskompetencer på tværs af organisatoriske niveauer præsenteres og diskuteres. Afslutningsvis diskuteres begrænsningerne i en kompetencebaseret tilgang til Leadership Pipeline, og det foreslås, at succesfuld ledelse i ligeså høj grad afhænger af...

  16. Identification of minor secondary metabolites from the latex of Croton lechleri (Muell-Arg) and evaluation of their antioxidant activity.

    Science.gov (United States)

    De Marino, Simona; Gala, Fulvio; Zollo, Franco; Vitalini, Sara; Fico, Gelsomina; Visioli, Francesco; Iorizzi, Maria

    2008-01-01

    Dragon's blood (Sangre de drago), a viscous red sap derived from Croton lechleri Muell-Arg (Euphorbiaceae), is extensively used by indigenous cultures of the Amazonian basin for its wound healing properties. The aim of this study was to identify the minor secondary metabolites and test the antioxidant activity of this sustance. A bioguided fractionation of the n-hexane, chloroform, n-butanol, and aqueous extracts led to the isolation of 15 compounds: three megastigmanes, four flavan-3-ols, three phenylpropanoids, three lignans, a clerodane, and the alkaloid taspine. In addition to these known molecules, six compounds were isolated and identified for the first time in the latex: blumenol B, blumenol C, 4,5-dihydroblumenol A, erythro-guaiacyl-glyceryl-beta-O-4'- dihydroconiferyl ether, 2-[4-(3-hydroxypropyl)-2-methoxyphenoxy]-propane-1,3-diol and floribundic acid glucoside. Combinations of spectroscopic methods ((1)H-, (13)C- NMR and 2D-NMR experiments), ESI-MS, and literature comparisons were used for compound identification. In vitro antioxidant activities were assessed by DPPH, total antioxidant capacity and lipid peroxidation assays. Flavan-3-ols derivatives (as major phenolic compounds in the latex) exhibited the highest antioxidant activity.

  17. Bioactivity-guided identification of antimicrobial metabolites in Alnus glutinosa bark and optimization of oregonin purification by Centrifugal Partition Chromatography.

    Science.gov (United States)

    Abedini, Amin; Chollet, Sébastien; Angelis, Apostolis; Borie, Nicolas; Nuzillard, Jean-Marc; Skaltsounis, Alexios-Leandros; Reynaud, Romain; Gangloff, Sophie C; Renault, Jean-Hugues; Hubert, Jane

    2016-09-01

    Barks from conifers and broadleaved trees constitute abundant wastes generated from wood harvesting and logging activities. Extracts of such residues obtained from Alnus trees have been reported as interesting resources with potent antibacterial activities. The present study aims to determine the antimicrobial activity of a crude methanol extract prepared from the bark of Alnus glutinosa against a panel of 22 bacteria and yeasts and to optimize a purification method enabling the high production of the most active substances. Fractionation of the crude extract was performed by Centrifugal Partition Chromatography (CPC) using a three-phase solvent system composed of n-heptane, methyl-ter-butyl ether, acetonitrile and water. The major known compounds contained in the fractions produced by CPC were chemically profiled by (13)C NMR dereplication, resulting in the unambiguous identification of oregonin, hirsutanonol, betulinic acid, and alusenone 1a. The antibacterial evaluation of the fractions by bioautography on Staphylococcus aureus revealed that oregonin, in addition to being the major metabolite of the crude extract (∼32% w/w), was the most active with an antibacterial inhibitory effect comparable to antibiotics. The purification of oregonin was optimized at the laboratory-scale by CPC. A single injection of 3.7g of crude extract resulted in a recovery of 72% (850mg) of the available oregonin at purity higher than 94%.

  18. Identification of Minor Secondary Metabolites from the Latex of Croton lechleri (Muell-Arg and Evaluation of Their Antioxidant Activity

    Directory of Open Access Journals (Sweden)

    Maria Iorizzi

    2008-06-01

    Full Text Available Dragon’s blood (Sangre de drago, a viscous red sap derived from Croton lechleri Muell-Arg (Euphorbiaceae, is extensively used by indigenous cultures of the Amazonian basin for its wound healing properties. The aim of this study was to identify the minor secondary metabolites and test the antioxidant activity of this sustance. A bioguided fractionation of the n-hexane, chloroform, n-butanol, and aqueous extracts led to the isolation of 15 compounds: three megastigmanes, four flavan-3-ols, three phenylpropanoids, three lignans, a clerodane, and the alkaloid taspine. In addition to these known molecules, six compounds were isolated and identified for the first time in the latex: blumenol B, blumenol C, 4,5-dihydroblumenol A, erythro-guaiacyl-glyceryl-β-O-4’- dihydroconiferyl ether, 2-[4-(3-hydroxypropyl-2-methoxyphenoxy]-propane-1,3-diol and floribundic acid glucoside. Combinations of spectroscopic methods (1H-, 13C- NMR and 2D-NMR experiments, ESI-MS, and literature comparisons were used for compound identification. In vitro antioxidant activities were assessed by DPPH, total antioxidant capacity and lipid peroxidation assays. Flavan-3-ols derivatives (as major phenolic compounds in the latex exhibited the highest antioxidant activity.

  19. Identification of polybrominated diphenyl ether metabolites based on calculated boiling points from COSMO-RS, experimental retention times, and mass spectral fragmentation patterns.

    Science.gov (United States)

    Simpson, Scott; Gross, Michael S; Olson, James R; Zurek, Eva; Aga, Diana S

    2015-02-17

    The COnductor-like Screening MOdel for Realistic Solvents (COSMO-RS) was used to predict the boiling points of several polybrominated diphenyl ethers (PBDEs) and methylated derivatives (MeO-BDEs) of monohydroxylated BDE (OH-BDE) metabolites. The linear correlation obtained by plotting theoretical boiling points calculated by COSMO-RS against experimentally determined retention times from gas chromatography-mass spectrometry facilitated the identification of PBDEs and OH-BDEs. This paper demonstrates the applicability of COSMO-RS in identifying unknown PBDE metabolites of 2,2',4,4'-tetrabromodiphenyl ether (BDE-47) and 2,2',4,4',6-pentabromodiphenyl ether (BDE-100). Metabolites of BDE-47 and BDE-100 were formed through individual incubations of each PBDE with recombinant cytochrome P450 2B6. Using calculated boiling points and characteristic mass spectral fragmentation patterns of the MeO-BDE positional isomers, the identities of the unknown monohydroxylated metabolites were proposed to be 2'-hydroxy-2,3',4,4'-tetrabromodiphenyl ether (2'-OH-BDE-66) from BDE-47, and 2'-hydroxy-2,3',4,4',6-pentabromodiphenyl ether (2'-OH-BDE-119) and 4-hydroxy-2,2',3,4',6-pentabromodiphenyl ether (4-OH-BDE-91) from BDE-100. The collective use of boiling points predicted with COSMO-RS, and characteristic mass spectral fragmentation patterns provided a valuable tool toward the identification of isobaric compounds.

  20. A STRATEGY FOR THE RAPID IDENTIFICATION OF FUNGAL METABOLITES AND THE DISCOVERY OF THE ANTIVIRAL ACTIVITY OF PYRENOCINE A AND HARZIANOPYRIDONE

    Directory of Open Access Journals (Sweden)

    Laura P. Ióca

    2016-07-01

    Full Text Available The isolation and identification of bioactive metabolites from complex extracts obtained from microbial growth media is a time consuming, costly, and labor-intensive task. A strategy to rapidly identify secondary metabolites isolated from extracts obtained from the culture media of marine-derived and endophytic fungal strains is described. Identification was achieved by HPLC-UV-MS and 1H NMR analyses in combination with data obtained from the Dictionary of Natural Products. Among the compounds identified, (--naphthoquinoneimine, citreorosein, emodin, pyrenocine A and harzianopyridone displayed moderate to potent antiviral activity. (--Naphthoquinoneimine was isolated as the enantiomer of its previously reported dextrorotatory congener, while 6,7-dihydroxy-2,2-dimethyl-4-chromanone is herein reported for the first time as a natural product.

  1. Mass spectrometric evaluation of mephedrone in vivo human metabolism: identification of phase I and phase II metabolites, including a novel succinyl conjugate.

    Science.gov (United States)

    Pozo, Óscar J; Ibáñez, María; Sancho, Juan V; Lahoz-Beneytez, Julio; Farré, Magí; Papaseit, Esther; de la Torre, Rafael; Hernández, Félix

    2015-02-01

    In recent years, many new designer drugs have emerged, including the group of cathinone derivatives. One frequently occurring drug is mephedrone; although mephedrone was originally considered as a "legal high" product, it is currently banned in most Western countries. Despite the banning, abuse of the drug and seizures are continuously reported. Although the metabolism of mephedrone has been studied in rats or in vitro using human liver microsomes, to the best of our knowledge, no dedicated study with human volunteers has been performed for studying the in vivo metabolism of mephedrone in humans. Therefore, the aim of this study was to establish the actual human metabolism of mephedrone and to compare it with other models. For this purpose, urine samples of two healthy volunteers, who ingested 200 mg mephedrone orally, were taken before administration and 4 hours after substance intake. The discovery and identification of the phase I and phase II metabolites of mephedrone were based on ultra-high-performance liquid chromatography coupled to hybrid quadrupole time-of-flight mass spectrometry, operating in the so-called MS(E) mode. Six phase I metabolites and four phase II metabolites were identified, four of them not previously reported in the literature. The structure of four of the detected metabolites was confirmed by synthesis of the suggested compounds. Remarkably, a mephedrone metabolite conjugated with succinic acid has been identified and confirmed by synthesis. According to the reviewed literature, this is the first time that this type of conjugate is reported for human metabolism.

  2. Motif-independent de novo detection of secondary metabolite gene clusters-toward identification from filamentous fungi.

    Science.gov (United States)

    Umemura, Myco; Koike, Hideaki; Machida, Masayuki

    2015-01-01

    Secondary metabolites are produced mostly by clustered genes that are essential to their biosynthesis. The transcriptional expression of these genes is often cooperatively regulated by a transcription factor located inside or close to a cluster. Most of the secondary metabolism biosynthesis (SMB) gene clusters identified to date contain so-called core genes with distinctive sequence features, such as polyketide synthase (PKS) and non-ribosomal peptide synthetase (NRPS). Recent efforts in sequencing fungal genomes have revealed far more SMB gene clusters than expected based on the number of core genes in the genomes. Several bioinformatics tools have been developed to survey SMB gene clusters using the sequence motif information of the core genes, including SMURF and antiSMASH. More recently, accompanied by the development of sequencing techniques allowing to obtain large-scale genomic and transcriptomic data, motif-independent prediction methods of SMB gene clusters, including MIDDAS-M, have been developed. Most these methods detect the clusters in which the genes are cooperatively regulated at transcriptional levels, thus allowing the identification of novel SMB gene clusters regardless of the presence of the core genes. Another type of the method, MIPS-CG, uses the characteristics of SMB genes, which are highly enriched in non-syntenic blocks (NSBs), enabling the prediction even without transcriptome data although the results have not been evaluated in detail. Considering that large portion of SMB gene clusters might be sufficiently expressed only in limited uncommon conditions, it seems that prediction of SMB gene clusters by bioinformatics and successive experimental validation is an only way to efficiently uncover hidden SMB gene clusters. Here, we describe and discuss possible novel approaches for the determination of SMB gene clusters that have not been identified using conventional methods.

  3. Motif-independent de novo detection of secondary metabolite gene clusters—toward identification from filamentous fungi

    Science.gov (United States)

    Umemura, Myco; Koike, Hideaki; Machida, Masayuki

    2015-01-01

    Secondary metabolites are produced mostly by clustered genes that are essential to their biosynthesis. The transcriptional expression of these genes is often cooperatively regulated by a transcription factor located inside or close to a cluster. Most of the secondary metabolism biosynthesis (SMB) gene clusters identified to date contain so-called core genes with distinctive sequence features, such as polyketide synthase (PKS) and non-ribosomal peptide synthetase (NRPS). Recent efforts in sequencing fungal genomes have revealed far more SMB gene clusters than expected based on the number of core genes in the genomes. Several bioinformatics tools have been developed to survey SMB gene clusters using the sequence motif information of the core genes, including SMURF and antiSMASH. More recently, accompanied by the development of sequencing techniques allowing to obtain large-scale genomic and transcriptomic data, motif-independent prediction methods of SMB gene clusters, including MIDDAS-M, have been developed. Most these methods detect the clusters in which the genes are cooperatively regulated at transcriptional levels, thus allowing the identification of novel SMB gene clusters regardless of the presence of the core genes. Another type of the method, MIPS-CG, uses the characteristics of SMB genes, which are highly enriched in non-syntenic blocks (NSBs), enabling the prediction even without transcriptome data although the results have not been evaluated in detail. Considering that large portion of SMB gene clusters might be sufficiently expressed only in limited uncommon conditions, it seems that prediction of SMB gene clusters by bioinformatics and successive experimental validation is an only way to efficiently uncover hidden SMB gene clusters. Here, we describe and discuss possible novel approaches for the determination of SMB gene clusters that have not been identified using conventional methods. PMID:25999925

  4. Continuous degradation of a mixture of sulfonamides by Trametes versicolor and identification of metabolites from sulfapyridine and sulfathiazole

    Energy Technology Data Exchange (ETDEWEB)

    Rodriguez-Rodriguez, Carlos E., E-mail: CarlosEsteban.Rodriguez@uab.cat [Unitat asociada de Biocatalisi Aplicada IQAC-CSIC, Escola d' Enginyeria, Universitat Autonoma de Barcelona, 08193 Bellaterra, Barcelona (Spain); Centro de Investigacion en Contaminacion Ambiental, Universidad de Costa Rica, 2060 San Jose (Costa Rica); Jesus Garcia-Galan, Ma. [Departament de Quimica Ambiental, IDAEA-CSIC, C/Jordi Girona 18-26, 08034, Barcelona (Spain); Blanquez, Paqui [Departament d' Enginyeria Quimica, Escola d' Enginyeria, Universitat Autonoma de Barcelona, 08193 Bellaterra, Barcelona (Spain); Diaz-Cruz, M. Silvia [Departament de Quimica Ambiental, IDAEA-CSIC, C/Jordi Girona 18-26, 08034, Barcelona (Spain); Barcelo, Damia [Departament de Quimica Ambiental, IDAEA-CSIC, C/Jordi Girona 18-26, 08034, Barcelona (Spain); Catalan Institute for Water Research (ICRA), Parc Cientific i Tecnologic de la Universitat de Girona, C/Emili Grahit, 101 Edifici H2O, E-17003 Girona (Spain); Caminal, Gloria [Unitat asociada de Biocatalisi Aplicada IQAC-CSIC, Escola d' Enginyeria, Universitat Autonoma de Barcelona, 08193 Bellaterra, Barcelona (Spain); Vicent, Teresa [Departament d' Enginyeria Quimica, Escola d' Enginyeria, Universitat Autonoma de Barcelona, 08193 Bellaterra, Barcelona (Spain)

    2012-04-30

    Highlights: Black-Right-Pointing-Pointer Degradation of sulfapyridine and sulfathiazole by Trametes versicolor was evaluated. Black-Right-Pointing-Pointer The role of laccase and cytochrome P450 was determined. Black-Right-Pointing-Pointer Degradation metabolites were identified for sulfapyridine (8) and sulfathiazole (5). Black-Right-Pointing-Pointer A mixture of three sulfonamides was degraded in a continuous fluidized bed reactor. - Abstract: In this study, we assessed the degradation of the sulfonamides sulfapyridine (SPY) and sulfathiazole (STZ) by the white-rot fungus Trametes versicolor. Complete degradation was accomplished in fungal cultures at initial pollutant concentrations of approximately 10 mg L{sup -1}, although a longer period of time was needed to completely remove STZ in comparison to SPY. When cytochrome P450 inhibitors were added to the fungal cultures, STZ degradation was partially suppressed, while no additional effect was observed for SPY. Experiments with purified laccase and laccase mediators caused the removal of greater than 75% of each antibiotic. Ultra-performance liquid chromatography-quadupole time of flight mass spectrometry (UPLC-QqTOF-MS) analyses allowed the identification of a total of eight degradation intermediates of SPY in both the in vivo and the laccase experiments, being its desulfonated moiety the commonly detected product. For STZ, a total of five products were identified. A fluidized bed reactor with T. versicolor pellets degraded a mixture of sulfonamides (SPY, STZ and sulfamethazine, SMZ) by greater than 94% each at a hydraulic residence time of 72 h. Because wastewater contains many diverse pollutants, these results highlight the potential of T. versicolor as a bioremediation agent not only for the removal of antibiotics but also for the elimination of a wide range of contaminants.

  5. Anchor Loads on Pipelines

    OpenAIRE

    Wei, Ying

    2015-01-01

    Anchor hooking on a subsea pipeline has been investigated in this thesis. Anchor loads on pipelines is in general a rarely occurring event, however, the severity when it occurs could easily jeopardize the integrity of any pipeline. It is considered as an accidental load in the design of pipelines. Pipeline Loads, limit state criteria and anchor categories are defined by the DNV standards. For pipeline, DNV-OS-F101 (08.2012), Submarine Pipeline Systems is adopted. Offshore standard DNV-RP...

  6. Identification of ginkgolide B metabolites in urine and rat liver cytochrome P450 enzymes responsible for their formation in vitro

    Institute of Scientific and Technical Information of China (English)

    Dian-lei WANG; Yan LIANG; Wei-dong CHEN; Lin XIE; Guang-ji WANG; Xiao-dong LIU

    2008-01-01

    Aim:To identify metabolites of ginkgolide B in rat urine,the predominant metabo-lism of ginkgolide B and the major cytochrome (CYP) P450 enzymes responsible for the metabolism of ginkgolide B in rat liver microsomes.Methods:A liquid chromatography quadrupole mass spectrometer and liquid chromatography ion-trap-time-of-flight mass spectrometer with electrospray ionization in negative-ion mode were used for the structure elucidation of metabolites in rat urine and liver microsome incubation.Various selective CYP450 inhibitors were applied to inves-tigate their effects on the metabolism of ginkgolide B and the formation of the major metabolite in rat liver microsomes.Results:Three metabolites were identi-fied in rat urine.One hydroxyl metabolite of ginkgolide B were identified in rat liver microsomes,and quinidine uncompetitively inhibited the formation of the metabolite;its inhibitor constant (Ki) value for the inhibition of hydroxyl metabo-lite was estimated to be 8 μmol/L,whileα-naphthoflavone,ketoconazole,sulfaphenazole,and diethyidithiocarbamate had no inhibitory effects.Conclusion:Ginkgolide B was metabolized to its hydroxyl metabolite in rats,and CYP2D6 was the major rat CYP isoform responsible for the ginkgolide B metabolism in rat liver microsomes.

  7. Detection and identification of plasma progesterone metabolites in the female Florida manatee (Trichechus manatus latirostris) using GC/MS/MS.

    Science.gov (United States)

    Tripp, K M; Dubois, M; Delahaut, P; Verstegen, J P

    2009-08-01

    Florida manatees (Trichechus manatus latirostris) have relatively low peripheral concentrations of progesterone (P4). The objective of this study was to determine if these relatively low P4 concentrations are associated with a high ratio of progestin metabolites and to document metabolite concentrations from individual blood samples obtained from manatees during diestrus or pregnancy. Metabolites known to exist in elephants-terrestrial manatee relatives-were targeted. These included 5alpha-reduced progestins (5alpha-pregnane-3,20-dione [5alpha-DHP] and 3alpha-hydroxy-5alpha-pregnan-20-one [5alpha-P3-OH]) and 17alpha-hydroxyprogesterone (17alpha-OHP), which occurs in Asian elephants. An additional, inactive metabolite, 20alpha-hydroxyprogesterone (20alpha-OHP), indicative of P4 overproduction, was also targeted. Progesterone itself was the predominant progestin detected in pregnant and nonpregnant manatee plasma (n = 10) using gas chromatography-mass spectrometry with tandem quadrupole detectors (GC/MS/MS). Progesterone concentrations in pregnant females varied from early (moderate to high) through mid and late (low) pregnancy. Progesterone concentrations ranged from low to high in nonpregnant, nonlactating females. The most commonly detected metabolite was 5alpha-P3-OH (n = 7), which occurred in pregnant (lower limit of detection [LLOD] to high) and nonpregnant (trace to high) females. The 5alpha-DHP metabolite was also detected in pregnant (LLOD to moderate) and nonpregnant (low) females. The 17alpha-OHP metabolite was not detected in any tested female. The 20alpha-OHP metabolite was detected in one nonpregnant, nonlactating, captive female (LLOD). Metabolites were most prevalent during early pregnancy, concurrent with maximum P4 concentrations. Based on their concentrations in peripheral circulation, we inferred that these metabolites may have, opposite to elephants, a limited physiologic role during luteal, pregnant, and nonpregnant phases in the manatee.

  8. Synthesis, microsome-mediated metabolism, and identification of major metabolites of environmental pollutant naphtho(8,1,2-ghi)chrysene

    Energy Technology Data Exchange (ETDEWEB)

    Sharma, A.K.; Gowdahalli, K.; Gimbor, M.; Amin, S. [Penn State College of Medicine, Hershey, PA (United States)

    2008-05-15

    Naphtho(8,1,2-ghi)chrysene, commonly known as naphtho(1,2-e)pyrene (N(1,2-e)P) is a widespread environmental pollutant, identified in coal tar extract, air borne particulate matter, marine sediment, cigarette smoke condensate, and vehicle exhaust. Herein, we determined the ability of rat liver microsomes to metabolize N(1,2-e)P and an unequivocal assignment of the metabolites by comparing them with independently,synthesized standards. We developed the synthesis of both the fjord region and the K-region dihydrodiols and various phenolic derivatives for metabolite identification. In summary, N(1,2-e)P trans-11, 12-dihydrodiol was the major metabolite formed along with N(1,2-e)P 4,5-trtins-dihydrodiol and 12-OH-N(1,2-e)P on exposure of rat liver microsomes to N(1,2-e)P. The presence of N(1,2-e)P in the environment and formation of fjord region dihydrodiol 14 as a major metabolite in in vitro metabolism studies strongly suggest the role of N(1,2-e)P as a potential health hazard.

  9. Identification of in vitro metabolites of Indinavir by "intelligent automated LC-MS/MS" (INTAMS) utilizing triple quadrupole tandem mass spectrometry.

    Science.gov (United States)

    Yu, X; Cui, D; Davis, M R

    1999-02-01

    In an effort to improve the efficiency of the TSQ 7000 LC-MS/MS system for identification of drug metabolites in biological matrices in support of drug discovery programs, a combination of instrument control language procedures for the Finnigan MAT TSQ 7000 mass spectrometer, referred to as INTAMS, were composed. INTAMS was designed to conduct unattended, automatic liquid chromatography/mass spectrometry (LC-MS) and LC-MS/MS analyses of drugs and metabolites in commonly encountered in vitro biological matrices. A novel peak detection algorithm was developed to automatically detect and record the pseudomolecular ions and retention times of chromatographic components, even if not fully resolved. This algorithm was used in combination with an automated technique for predicting the molecular weights of metabolites based on incremental changes of the molecular weight of the parent drug resulting from well-known biotransformation processes. When applied to a sample of an incubation mixture of the HIV protease inhibitor Indinavir with a rat liver S9 preparation, the results obtained by the automatic metabolite detection procedures for LC-MS and LC-MS/MS analyses in real time were the same as those which were determined manually, by a knowledgeable operator.

  10. Identification of 3′,4′-Dimethoxy Flavonol-3-β-d-Glucopyranoside Metabolites in Rats by Liquid Chromatography-Electrospray Ionization Ion Trap Mass Spectrometry

    Directory of Open Access Journals (Sweden)

    Yuan Zhu

    2016-04-01

    Full Text Available A method using liquid chromatography-electrospray ionization ion trap mass spectrometry was established for the identification of metabolites in feces, urine and bile in rats after oral administration of 3′,4′-dimethoxy flavonol-3-β-d-glucopyranoside (abbreviated DF3G. Seven metabolites in rat feces, urine and bile were firstly identified on the basis of their MS fragmentation behaviors. Three metabolites were identified in the feces, 6 in the urine and 2 in the bile, which suggested that demethylation, deglycosylation and deglycosylation followed by glucuronide conjugation were the major metabolic pathways for DF3G in vivo. Hydrolyzation might be the first step in the absorption and metabolism of DF3G. The possible metabolic pathway was proposed for the first time. The established method was simple, reliable and sensitive, revealing that it could be used to rapidly screen and identify the structures of metabolites of DF3G to better understand its metabolism in vivo.

  11. The Impact of Genotyping-by-Sequencing Pipelines on SNP Discovery and Identification of Markers Associated with Verticillium Wilt Resistance in Autotetraploid Alfalfa (Medicago sativa L.)

    Science.gov (United States)

    Yu, Long-Xi; Zheng, Ping; Bhamidimarri, Suresh; Liu, Xiang-Ping; Main, Dorie

    2017-01-01

    Verticillium wilt (VW) of alfalfa is a soilborne disease causing severe yield loss in alfalfa. To identify molecular markers associated with VW resistance, we used an integrated framework of genome-wide association study (GWAS) with high-throughput genotyping by sequencing (GBS) to identify loci associated with VW resistance in an F1 full-sib alfalfa population. Phenotyping was performed using manual inoculation of the pathogen to cloned plants of each individual and disease severity was scored using a standard scale. Genotyping was done by GBS, followed by genotype calling using three bioinformatics pipelines including the TASSEL-GBS pipeline (TASSEL), the Universal Network Enabled Analysis Kit (UNEAK), and the haplotype-based FreeBayes pipeline (FreeBayes). The resulting numbers of SNPs, marker density, minor allele frequency (MAF) and heterozygosity were compared among the pipelines. The TASSEL pipeline generated more markers with the highest density and MAF, whereas the highest heterozygosity was obtained by the UNEAK pipeline. The FreeBayes pipeline generated tetraploid genotypes, with the least number of markers. SNP markers generated from each pipeline were used independently for marker-trait association. Markers significantly associated with VW resistance identified by each pipeline were compared. Similar marker loci were found on chromosomes 5, 6, and 7, whereas different loci on chromosome 1, 2, 3, and 4 were identified by different pipelines. Most significant markers were located on chromosome 6 and they were identified by all three pipelines. Of those identified, several loci were linked to known genes whose functions are involved in the plants’ resistance to pathogens. Further investigation on these loci and their linked genes would provide insight into understanding molecular mechanisms of VW resistance in alfalfa. Functional markers closely linked to the resistance loci would be useful for MAS to improve alfalfa cultivars with enhanced resistance

  12. Identification, quantification, spatiotemporal distribution and genetic variation of major latex secondary metabolites in the common dandelion (Taraxacum officinale agg.).

    Science.gov (United States)

    Huber, Meret; Triebwasser-Freese, Daniella; Reichelt, Michael; Heiling, Sven; Paetz, Christian; Chandran, Jima N; Bartram, Stefan; Schneider, Bernd; Gershenzon, Jonathan; Erb, Matthias

    2015-07-01

    The secondary metabolites in the roots, leaves and flowers of the common dandelion (Taraxacum officinale agg.) have been studied in detail. However, little is known about the specific constituents of the plant's highly specialized laticifer cells. Using a combination of liquid and gas chromatography, mass spectrometry and nuclear magnetic resonance spectrometry, we identified and quantified the major secondary metabolites in the latex of different organs across different growth stages in three genotypes, and tested the activity of the metabolites against the generalist root herbivore Diabrotica balteata. We found that common dandelion latex is dominated by three classes of secondary metabolites: phenolic inositol esters (PIEs), triterpene acetates (TritAc) and the sesquiterpene lactone taraxinic acid β-D-glucopyranosyl ester (TA-G). Purification and absolute quantification revealed concentrations in the upper mgg(-1) range for all compound classes with up to 6% PIEs, 5% TritAc and 7% TA-G per gram latex fresh weight. Contrary to typical secondary metabolite patterns, concentrations of all three classes increased with plant age. The highest concentrations were measured in the main root. PIE profiles differed both quantitatively and qualitatively between plant genotypes, whereas TritAc and TA-G differed only quantitatively. Metabolite concentrations were positively correlated within and between the different compound classes, indicating tight biosynthetic co-regulation. Latex metabolite extracts strongly repelled D. balteata larvae, suggesting that the latex constituents are biologically active. Copyright © 2015 Elsevier Ltd. All rights reserved.

  13. Unambiguous metabolite identification in high-throughput metabolomics by hybrid 1D 1 H NMR/ESI MS 1 approach: Hybrid 1D 1 H NMR/ESI MS 1 metabolomics method

    Energy Technology Data Exchange (ETDEWEB)

    Walker, Lawrence R. [Environmental Molecular Sciences Laboratory, Pacific Northwest National Laboratory, Richland WA 99354 USA; Hoyt, David W. [Environmental Molecular Sciences Laboratory, Pacific Northwest National Laboratory, Richland WA 99354 USA; Walker, S. Michael [Department of Ecology and Evolutionary Biology, University of Kansas, Lawrence KS 66045 USA; Ward, Joy K. [Department of Ecology and Evolutionary Biology, University of Kansas, Lawrence KS 66045 USA; Nicora, Carrie D. [Environmental Molecular Sciences Laboratory, Pacific Northwest National Laboratory, Richland WA 99354 USA; Bingol, Kerem [Environmental Molecular Sciences Laboratory, Pacific Northwest National Laboratory, Richland WA 99354 USA

    2016-09-16

    We present a novel approach to improve accuracy of metabolite identification by combining direct infusion ESI MS1 with 1D 1H NMR spectroscopy. The new approach first applies standard 1D 1H NMR metabolite identification protocol by matching the chemical shift, J-coupling and intensity information of experimental NMR signals against the NMR signals of standard metabolites in metabolomics library. This generates a list of candidate metabolites. The list contains false positive and ambiguous identifications. Next, we constrained the list with the chemical formulas derived from high-resolution direct infusion ESI MS1 spectrum of the same sample. Detection of the signals of a metabolite both in NMR and MS significantly improves the confidence of identification and eliminates false positive identification. 1D 1H NMR and direct infusion ESI MS1 spectra of a sample can be acquired in parallel in several minutes. This is highly beneficial for rapid and accurate screening of hundreds of samples in high-throughput metabolomics studies. In order to make this approach practical, we developed a software tool, which is integrated to Chenomx NMR Suite. The approach is demonstrated on a model mixture, tomato and Arabidopsis thaliana metabolite extracts, and human urine.

  14. Identification of Volatile Metabolites from Fungal Endophytes with Biocontrol Potential towards Fusarium oxysporum F. sp. cubense Race 4

    Directory of Open Access Journals (Sweden)

    A. S. Y. Ting

    2010-01-01

    Full Text Available Problem statement: Fungal endophytes are widely studied for their potential as biocontrol agents towards fungal pathogens. In vitro assessments usually reveal their antibiosis and mycoparasitism nature, but little is understood regarding their production of volatile metabolites as mechanisms of antagonism. Approach: This study explored the potential of fungal endophytes in controlling the pathogen responsible for Fusarium wilt disease. Nine fungal endophytes were tested for their ability to inhibit the growth of the pathogenic Fusarium oxysporum F. sp. cubense race 4 (FocR4 via production of volatile inhibitory metabolites. The type of volatile metabolites produced were subsequently characterized and identified using the Gas-Chromatography Mass-Spectrophotometry (GCMS. Results: Eight of the isolates (BTF05, BTF07, BTF08, BTF15, BTF21, WAA03, WAA02, MIF01 showed positive results with percentages of inhibition varying from 1.43-31.43% while one isolate (ALF01, showed negative result (0% inhibition. Volatile profiles showed that these fungal endophytes produced between 15-47 volatile metabolites per isolate. However, the more volatile metabolites produced by a single endophyte does not indicate better biocontrol potential. Isolate BTF05 produced 47 different volatile metabolites, but has only 8.57% inhibition, compared to isolate BTF21 with 15 metabolites but a percentage of 11.43% inhibition. The potency of the volatile metabolites produced may also influenced the biocontrol potential of the fungal endophytes as some isolates such as BTF08 and MIF01 have only two to three known inhibitory metabolites but have higher PIDG values at 31.43 and 11.43%, respectively. Contrary, isolates WAA02 and WAA03 which has five to six metabolites but PIDG values of less than 3%. Conclusion: Fungal endophytes have the ability to produce several types of volatile metabolites to inhibit the growth of FocR4. These volatile inhibitory metabolites can be further

  15. High-resolution mass spectrometry applied to the identification of transformation products of quinolones from stability studies and new metabolites of enrofloxacin in chicken muscle tissues.

    Science.gov (United States)

    Morales-Gutiérrez, F J; Hermo, M P; Barbosa, J; Barrón, D

    2014-04-01

    The aim of this work was the identification of new metabolites and transformation products (TPs) in chicken muscle from enrofloxacin (ENR), ciprofloxacin (CIP), difloxacin (DIF) and sarafloxacin (SAR), which are antibiotics that belong to the fluoroquinolones family. The stability of ENR, CIP, DIF and SAR standard solutions versus pH degradation process (from pH 1.5 to 8.0, simulating the pH since the drug is administered until its excretion) and freeze-thawing (F/T) cycles was tested. In addition, chicken muscle samples from medicated animals with ENR were analyzed in order to identify new metabolites and TPs. The identification of the different metabolites and TPs was accomplished by comparison of mass spectral data from samples and blanks, using liquid chromatography coupled to quadrupole time-of-flight (LC-QqToF) and multiple mass defect filter (MMDF) technique as a pre-filter to remove most of the background noise and endogenous components. Confirmation and structure elucidation was performed by liquid chromatography coupled to linear ion trap quadrupole Orbitrap (LC-LTQ-Orbitrap), due to its mass accuracy and MS/MS capacity for elemental composition determination. As a result, 21 TPs from ENR, 6 TPs from CIP, 14 TPs from DIF and 12 TPs from SAR were identified due to the pH shock and F/T cycles. On the other hand, 14 metabolites were identified from the medicated chicken muscle samples. Formation of CIP and SAR, from ENR and DIF, respectively, and the formation of desethylene-quinolone were the most remarkable identified compounds.

  16. Identification of in vitro metabolites of ethylphenidate by liquid chromatography coupled to quadrupole time-of-flight mass spectrometry

    OpenAIRE

    Negreira, Noelia; Erratico, Claudio; Nuijs, van, Alexander L.N.; Covaci, Adrian

    2016-01-01

    Abstract: Ethylphenidate is a new potent synthetic psychoactive drug, structurally related to methylphenidate. Using human liver microsomes and cytosol, we have investigated for the first time the Phase-I and Phase-II in vitro metabolism of ethylphenidate. The structure of the metabolites was elucidated by hybrid quadrupole time-of-flight mass spectrometry. Overall, seven Phase-I, but no Phase-II metabolites were detected. Ethylphenidate underwent hydroxylation forming two primary mono-hydrox...

  17. Identification of in vitro metabolites of ethylphenidate by liquid chromatography coupled to quadrupole time-of-flight mass spectrometry.

    Science.gov (United States)

    Negreira, Noelia; Erratico, Claudio; van Nuijs, Alexander L N; Covaci, Adrian

    2016-01-05

    Ethylphenidate is a new potent synthetic psychoactive drug, structurally related to methylphenidate. Using human liver microsomes and cytosol, we have investigated for the first time the Phase-I and Phase-II in vitro metabolism of ethylphenidate. The structure of the metabolites was elucidated by hybrid quadrupole time-of-flight mass spectrometry. Overall, seven Phase-I, but no Phase-II metabolites were detected. Ethylphenidate underwent hydroxylation forming two primary mono-hydroxylated metabolites and, subsequently, dehydration and ring opening with an additional hydroxylation, forming secondary metabolites. The involvement of different human cytochrome P450 (CYP) enzymes in the formation of ethylphenidate metabolites was investigated using a panel of human recombinant CYPs (rCYPs). rCYP2C19 was the most active recombinant enzyme involved in the formation of all seven ethylphenidate metabolites detected, although other rCYPs (rCYP1A2, rCYP2B6, rCYPC9, rCYP2D6, and rCYP3A4, but not rCYP2E1) played a role in the metabolism of ethylphenidate. All metabolites identified in the present study can be considered as potential specific biomarkers of ethylphenidate in toxicological studies. Additionally, ritalinic acid and methylphenidate were formed by non-enzymatic hydrolysis and trans-esterification, and, therefore, they cannot be considered as (oxidative) metabolites of ethylphenidate. The presence of methylphenidate and ritalinic acid cannot be exclusively associated to the use of ethylphenidate, since methylphenidate is a drug itself and ritanilic acid can be formed from both ethylphenidate and methylphenidate.

  18. 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.

  19. Identification of metabolites of fosinopril produced by human and rat liver microsomes with liquid chromatography-mass spectrometry.

    Science.gov (United States)

    Uutela, Päivi; Monto, Matti; Iso-Mustajärvi, Ilona; Madetoja, Mari; Yliperttula, Marjo; Ketola, Raimo A

    2014-03-12

    Metabolic profiles of prodrug fosinopril and pharmacologically active metabolite fosinoprilat were studied using human or rat liver microsomes and S9 fractions. Metabolites were identified by ultra high-performance liquid chromatography/quadrupole time-of-flight mass spectrometry (UHPLC/Q-TOF-MS) using electrospray ionization in the positive and negative ion mode. They were characterized by accurate MS and MS/MS spectra and based on their different fragmentation pathways. With human liver microsomes fosinopril was metabolized via hydroxylation, glucuronidation, and hydrolysis to fosinoprilat. As expected the main metabolite was fosinoprilat and it was further hydroxylated and glucuronidated. However, these metabolites were not detected after incubation of fosinoprilat with human liver microsomes, indicating that metabolic reactions occur in sequence and fosinopril is hydrolyzed after glucuronidation or hydroxylation. With the developed UHPLC/Q-TOF-MS method once or twice hydroxylated fosinopril metabolites were detected for the first time and different regioisomers were separated. It was observed that the hydrolysis of fosinopril to fosinoprilat was more efficient with rat than with human liver microsomes, and therefore more hydroxylated fosinoprilat metabolites were detected when rat liver microsomes were used. Glucuronidation of fosinopril was not observed with rat liver microsomes.

  20. Age as a determinant of phosphate flame retardant exposure of the Australian population and identification of novel urinary PFR metabolites.

    Science.gov (United States)

    Van den Eede, Nele; Heffernan, Amy L; Aylward, Lesa L; Hobson, Peter; Neels, Hugo; Mueller, Jochen F; Covaci, Adrian

    2015-01-01

    The demand for alternative flame retardant materials such as phosphate flame retardants and plasticizers (PFRs) is increasing, although little is known of their possible effects on human health and development. To date, no information on the exposure of children or general Australian population to PFRs is available. The objectives of this study were to characterize the average levels and age-related patterns of PFR metabolites in urine in the general Australian population and to identify novel hydroxylated PFR metabolites in urine. Surplus pathology urine samples from Queensland, Australia were stratified and pooled by age and sex (3224 individuals aged 0 to 75years into 95 pools) according to two different pooling strategies at two different time periods. Samples were analyzed by solid phase extraction and liquid chromatography-tandem mass spectrometry following enzymatic treatment. Nine PFR metabolites were measured in the Australian population, including the first report of a hydroxylated metabolite of TCIPP (BCIPHIPP). Diphenyl phosphate (DPHP), BCIPHIPP and bis(1,3-dichloro-2-propyl) phosphate (BDCIPP) were detected in >95% of samples. DPHP, a metabolite of aryl-PFRs, was found in several samples at levels which were one order of magnitude higher than previously reported (up to 730ng/mL). Weighted linear regression revealed a significant negative association between log-normalized BDCIPP and DPHP levels and age (pPFR biomonitoring studies.

  1. Identification of stereoisomeric metabolites of meisoindigo in rat liver microsomes by achiral and chiral liquid chromatography/tandem mass spectrometry.

    Science.gov (United States)

    Huang, Meng; Goh, Lin Tang; Ho, Paul C

    2008-11-01

    N-methylisoindigotin, abbreviated as meisoindigo, has been a routine therapeutic agent in the clinical treatment of chronic myelogenous leukemia in China since the 1980s. However, information relevant to in vitro metabolism of meisoindigo is limited. In this study, in vitro stereoisomeric metabolites of meisoindigo in rat liver microsomes were identified for the first time by achiral and chiral liquid chromatography/tandem mass spectrometry, together with proton NMR spectroscopy and synchrotron infrared spectroscopy. The major in vitro phase I metabolites of meisoindigo were tentatively identified as stereoselective-reduced meisoindigo, which comprised a pair of (3-R, 3'-R) and (3-S, 3'-S) enantiomers with lower abundance, as well as another pair of (3-R, 3'-S) and (3-S, 3'-R) enantiomers with higher abundance. One type of minor in vitro metabolites was tentatively identified as stereoselective N-demethyl-reduced meisoindigo including a pair of (3-R, 3'-R) and (3-S, 3'-S) enantiomers, as well as one meso compound. Another type of minor in vitro metabolites was tentatively identified as both stereoselective and regioselective monohydroxyl-reduced meisoindigo. Based on the metabolite profiling, three parallel metabolic pathways of meisoindigo in rat liver microsomes were proposed.

  2. Identification of fentanyl metabolites in rat urine by gas chromatography-mass spectrometry with stable-isotope tracers

    Energy Technology Data Exchange (ETDEWEB)

    Goromaru, T.; Matsuura, H.; Furuta, T.; Baba, S.; Yoshimura, N.; Miyawaki, T.; Sameshima, T.

    The metabolites of fentanyl (l), which has been widely used as a neuroleptic analgesic agent, were identified in urine of rats by gas chromatography-mass spectrometry combined with a stable-isotope tracer technique. After the oral administration of an equimolar mixture of l and deuterium-labeled l (l/l-d5), the urinary metabolites were extracted with chloroform at pH 9.0. Extracts were derivatized and analyzed by GC/MS. Metabolites were identified by the presence of doublet ion peaks separated by 5 amu, and chemical structures were established from analyses of fragmentation pathways. The metabolites were identified as 4-N-(N-propionylanilino)-piperidine, 4-N-(N-hydroxypropionylanilino)piperidine, 4-N-(N-propionylanilino) hydroxypiperidine, 1-(2-phenethyl)-4-N-(N-hydroxypropionylanilino)piperidine and 1-(2-phenethyl)-4-N-(N-propionylanilino)hydroxypiperidine. These metabolites, together with unchanged l, were also detected in urine of rats receiving l/l-d5 intravenously, by selected-ion monitoring of the specific cluster ions.

  3. Biotransformation of 17-alkylsteroids in the equine: gas chromatographic-mass spectral identification of ten intermediate metabolites of methyltestosterone.

    Science.gov (United States)

    Stanley, S M; Smith, L; Rodgers, J P

    1997-03-01

    The metabolism of the orally active anabolic steroid methyltestosterone in the equine was investigated by administration of the drug along with a tritiated radiolabel tracer. In this study some of the metabolites were identified and a radio immunoassay screen and immunoaffinity chromatography gel for methyltestosterone were also evaluated. Pathway intermediates, in particular the 17-methylandrostanediols, were studied to gain an insight into the most likely stereochemistry of the major metabolites. The predominant phase I biotransformations involve reduction of the A ring 3-oxo and 4-ene groups to yield predominantly 3 beta-hydroxy-5 alpha-androstane products and hydroxylation of the steroid nucleus at several positions. Epimerisation of the 17 alpha-methyl group also occurred. Ten steroids could be positively identified by comparison with authentic reference materials and many other triol, tetrol and pentols were also observed. Phase II metabolites and sulphate conjugates in particular, were common.

  4. Identification of an overabundant cholesterol precursor in hepatitis B virus replicating cells by untargeted lipid metabolite profiling.

    Science.gov (United States)

    Rodgers, Mary A; Saghatelian, Alan; Yang, Priscilla L

    2009-04-15

    Viruses rely upon host lipid metabolic pathways for successful replication, and there is increasing interest in these pathways as novel therapeutic targets for antiviral drug discovery. Despite this, relatively little is known about the impact of viral infection on cellular lipid metabolism, and the specific lipid metabolites utilized by viruses have not yet been examined. We have applied liquid chromatography-mass spectroscopy (LC-MS) based untargeted metabolite profiling to identify lipid metabolites whose steady-state abundance is significantly altered by replication of hepatitis B virus (HBV), a major human pathogen. Untargeted metabolite profiling indicated that although major lipid classes were unaffected by HBV, an ion of 367 m/z was overabundant in HBV+ cells by 18-fold. As shown by ion fragmentation mass spectrometry and coinjection with standard, the identity of this ion is 7-dehydrocholesterol (7-DHC), an immediate dehydrogenated precursor to cholesterol. While cholesterol has previously been demonstrated to be essential in the replication of many viruses, this is the first to show that viral replication is associated with the selective accumulation of 7-DHC. Most virological studies to date have relied upon methods that deplete all sterols and preclude the observation of any selectivity in sterol utilization by viral pathogens. Our study suggests that HBV may selectively utilize 7-DHC versus other sterols and prompts experiments investigating the functional significance of this enrichment and the elucidation of the mechanism by which it is achieved. The results also highlight the value of untargeted metabolite profiling as a method for identifying critical metabolites for viral infection.

  5. Identification of urolithin a as a metabolite produced by human colon microflora from ellagic acid and related compounds.

    Science.gov (United States)

    Cerdá, Begoña; Periago, Paula; Espín, Juan Carlos; Tomás-Barberán, Francisco A

    2005-07-13

    Dietary ellagic acid and related polyphenols are metabolized in humans to dibenzopyran-6-one derivatives, and the microbial origin of these metabolites has been suggested. However, this has not been demonstrated so far. Fecal samples donated by six volunteers were incubated under anaerobic conditions, and aliquots were used to evaluate the fecal metabolism of ellagic acid, the ellagitannin punicalagin, and an ellagitannin rich extract from walnuts. The isoflavone daidzein was also incubated with the same fecal samples to follow the production of the microbial metabolites previously reported (dihydrogenistein, O-demethylangolensin, and equol) as a positive control of the system and to evaluate similarities between isoflavone and ellagic acid fecal flora metabolism. After fermentation the metabolite "urolithin A" (3,8-dihydroxy-6H-dibenzo[b,d]pyran-6-one) was produced from ellagic acid, punicalagin, and the ellagitannin extract in all the fecal cultures from different volunteers, but with very different production rates and concentrations. This large variability in the concentration of metabolite and kinetics of metabolite production is consistent with the large variability found in the excretion of these metabolites in urine in vivo after human consumption of ellagitannins, and with differences in the composition of the fecal microflora. No correlation between isoflavone and ellagic acid metabolism by fecal microflora was observed. The present study confirms the microbial origin of the recently reported in vivo generated hydroxy-6H-dibenzo[b,d]pyran-6-one derivatives in humans and is a further step in the study of the bioavailability and metabolism of ellagic acid and ellagitannins.

  6. Analytical power of LLE-HPLC-PDA-MS/MS in drug metabolism studies: identification of new nabumetone metabolites.

    Science.gov (United States)

    Nobilis, Milan; Mikušek, Jiří; Szotáková, Barbora; Jirásko, Robert; Holčapek, Michal; Chamseddin, Chamseddin; Jira, Thomas; Kučera, Radim; Kuneš, Jiří; Pour, Milan

    2013-06-01

    Nabumetone is a non-acidic, nonsteroidal anti-inflammatory prodrug. Following oral administration, the prodrug is converted in the liver to 6-methoxy-2-naphthylacetic acid (6-MNA), which was found to be the principal metabolite responsible for the NSAID effect. The pathway of nabumetone transformation to 6-MNA has not been clarified, with no intermediates between nabumetone and 6-MNA having been identified to date. In this study, a new, as yet unreported phase I metabolite was discovered within the evaluation of nabumetone metabolism by human and rat liver microsomal fractions. Extracts from the biomatrices were subjected to chiral LLE-HPLC-PDA and achiral LLE-UHPLC-MS/MS analyses to elucidate the chemical structure of this metabolite. UHPLC-MS/MS experiments detected the presence of a structure corresponding to elemental composition C15H16O3, which was tentatively assigned as a hydroxylated nabumetone. Identical nabumetone and HO-nabumetone UV spectra obtained from the PDA detector ruled out the presence of the hydroxy group in the aromatic moiety of nabumetone. Hence, the most likely structure of the new metabolite was 4-(6-methoxy-2-naphthyl)-3-hydroxybutan-2-one (3-hydroxy nabumetone). To confirm this structure, the standard of this nabumetone metabolite was synthesized, its spectral (UV, CD, NMR, MS/MS) and retention properties on chiral and achiral chromatographic columns were evaluated and compared with those of the authentic nabumetone metabolite. To elucidate the subsequent biotransformation of 3-hydroxy nabumetone, the compound was used as a substrate in incubation with human and rat liver microsomal fraction. A number of 3-hydroxy nabumetone metabolites (products of conjugation with glucuronic acid, O-desmethylation, carbonyl reduction and their combination) were discovered in the extracts from the incubated microsomes using LLE-HPLC-PDA-MS/MS experiments. On the other hand, when 3-hydroxy nabumetone was incubated with isolated rat hepatocytes, 6-MNA was

  7. UV and MS identification of Urolithins and Nasutins, the bioavailable metabolites of ellagitannins and ellagic acid in different mammals.

    Science.gov (United States)

    González-Barrio, Rocío; Truchado, Pilar; Ito, Hideyuki; Espín, Juan C; Tomás-Barberán, Francisco A

    2011-02-23

    Urolithins are microbial metabolites produced from ellagic acid after the intake of dietary ellagitannins by different animals. Urolithin metabolites have distinct UV spectra that enable their detection and differentiation by HPLC coupled with UV photodiode array detectors. Correlations between structural characteristics, including conjugation, with the UV spectra and retention times are established. The production of urolithin derivatives in different animals feeding on ellagitannins, including rodents (rats and mice), humans, pigs, squirrels, beavers, sheep, bull calves, birds, and insects, was investigated. All mammals produced urolithins, and their glucuronyl and sulfate conjugates were the main metabolites detected in plasma and urine. Unconjugated urolithins were detected in feces, ruminal content, and beaver castoreum. Different urolithin hydroxylation patterns were observed for different animal species, suggesting that the microbiota responsible for the metabolism of ellagitannins in each animal species produces dehydroxylases for the removal of specific hydroxyls from the ellagic acid residue. Metabolites were characterized using HR HPLC-TOF-MS and ion trap MS/MS. Insects and birds feeding on ellagitannin-containing foods did not produce urolithins, although they released ellagic acid. Beavers and pigs were able to produce dehydroxyellagic acid derivatives (nasutin A), showing that in some cases the removal of hydroxyl groups from the ellagic acid nucleus can be carried out before the lactone ring is opened to produce urolithins.

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

    Science.gov (United States)

    Fipronil is a phenylpyrazole insecticide commonly used in residential and agricultural applications. To understand more about the potential risks associated with fipronil, dosed Long Evans rats were evaluated for metabolites to develop a set of biomarkers for use in human exposur...

  9. Identification of 4-hydroxyheptachlorostyrene in polar bear plasma and its binding affinity to transthyretin : a metabolite of octachlorostyrene?

    NARCIS (Netherlands)

    Standau, C.D.; Meerts, I.A.T.M.; Letcher, R.J.; McAlees, A.J.; Chittim, B.; Brouwer, A.; Norstrom, R.J.

    2000-01-01

    A new compound, 4-hydroxyheptachlorostyrene (4-OH-HpCS), was identified as a major component in the chlorinated phenolic compound fraction of polar bear plasma. The structure was hypothesized to be 4-OH-HpCS based on mass spectral interpretation, the assumption that it was a metabolite of octachloro

  10. Identification of 4-hydroxyheptachlorostyrene in polar bear plasma and its binding affinity to transthyretin : a metabolite of octachlorostyrene?

    NARCIS (Netherlands)

    Standau, C.D.; Meerts, I.A.T.M.; Letcher, R.J.; McAlees, A.J.; Chittim, B.; Brouwer, A.; Norstrom, R.J.

    2000-01-01

    A new compound, 4-hydroxyheptachlorostyrene (4-OH-HpCS), was identified as a major component in the chlorinated phenolic compound fraction of polar bear plasma. The structure was hypothesized to be 4-OH-HpCS based on mass spectral interpretation, the assumption that it was a metabolite of

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

    Science.gov (United States)

    Fipronil is a phenylpyrazole insecticide commonly used in residential and agricultural applications. To understand more about the potential risks associated with fipronil, dosed Long Evans rats were evaluated for metabolites to develop a set of biomarkers for use in human exposur...

  12. Submarine Pipeline Routing Risk Quantitative Analysis

    Institute of Scientific and Technical Information of China (English)

    徐慧; 于莉; 胡云昌; 王金英

    2004-01-01

    A new method for submarine pipeline routing risk quantitative analysis was provided, and the study was developed from qualitative analysis to quantitative analysis.The characteristics of the potential risk of the submarine pipeline system were considered, and grey-mode identification theory was used. The study process was composed of three parts: establishing the indexes system of routing risk quantitative analysis, establishing the model of grey-mode identification for routing risk quantitative analysis, and establishing the standard of mode identification result. It is shown that this model can directly and concisely reflect the hazard degree of the routing through computing example, and prepares the routing selection for the future.

  13. Underground pipeline corrosion

    CERN Document Server

    Orazem, Mark

    2014-01-01

    Underground pipelines transporting liquid petroleum products and natural gas are critical components of civil infrastructure, making corrosion prevention an essential part of asset-protection strategy. Underground Pipeline Corrosion provides a basic understanding of the problems associated with corrosion detection and mitigation, and of the state of the art in corrosion prevention. The topics covered in part one include: basic principles for corrosion in underground pipelines, AC-induced corrosion of underground pipelines, significance of corrosion in onshore oil and gas pipelines, n

  14. 77 FR 70543 - Pipeline Safety: Meeting of the Gas Pipeline Advisory Committee and the Liquid Pipeline Advisory...

    Science.gov (United States)

    2012-11-26

    ... for natural gas pipelines and for hazardous liquid pipelines. Both committees were established under... TRANSPORTATION Pipeline and Hazardous Materials Safety Administration Pipeline Safety: Meeting of the Gas Pipeline Advisory Committee and the Liquid Pipeline Advisory Committee AGENCY: Pipeline and...

  15. Identification of phase I and II metabolites of the new designer drug α-pyrrolidinohexiophenone (α-PHP) in human urine by liquid chromatography quadrupole time-of-flight mass spectrometry (LC-QTOF-MS).

    Science.gov (United States)

    Paul, Michael; Bleicher, Sergej; Guber, Susanne; Ippisch, Josef; Polettini, Aldo; Schultis, Wolfgang

    2015-11-01

    Pyrrolidinophenones represent one emerging class of newly encountered drugs of abuse, also known as 'new psychoactive substances', with stimulating psychoactive effects. In this work, we report on the detection of the new designer drug α-pyrrolidinohexiophenone (α-PHP) and its phase I and II metabolites in a human urine sample of a drug abuser. Determination and structural elucidation of these metabolites have been achieved by liquid chromatography electrospray ionisation quadrupole time-of-flight mass spectrometry (LC-ESI-QTOF-MS). By tentative identification, the exact and approximate structures of 19 phase I metabolites and nine phase II glucuronides were elucidated. Major metabolic pathways revealed the reduction of the ß-keto moieties to their corresponding alcohols, didesalkylation of the pyrrolidine ring, hydroxylation and oxidation of the aliphatic side chain leading to n-hydroxy, aldehyde and carboxylate metabolites, and oxidation of the pyrrolidine ring to its lactam followed by ring cleavage and additional hydroxylation, reduction and oxidation steps and combinations thereof. The most abundant phase II metabolites were glucuronidated ß-keto-reduced alcohols. Besides the great number of metabolites detected in this sample, α-PHP is still one of the most abundant ions together with its ß-keto-reduced alcoholic dihydro metabolite. Monitoring of these metabolites in clinical and forensic toxicology may unambiguously prove the abuse of the new designer drug α-PHP.

  16. [Identification of the metabolites of Sinisan extract in rat plasma, urine, feces and bile after intragastric administration].

    Science.gov (United States)

    Lu, Lin-ling; Shu, Yan; Qian, Da-wei; Su, Shu-lan; Duan, Jin-ao; Qian, Ye-fei; Xue, Cai-fu

    2011-11-01

    Sinisan is a widely used traditional Chinese medicine (TCM) in treating various diseases; however, the in vivo metabolic profile of its multiple components remains unknown. In this paper, ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS) was applied to identify the metabolites of Sinisan extract in rat plasma, urine, feces and bile after intragastric administration. Using MS(E) and mass defect filter techniques, 41 metabolites of 10 parent compounds (naringin, naringenin, hesperidin, neohesperidin, liquiritin, liquiritigenin, glycyrrhizic acid, glycyrrhetinic acid, saikosaponin a and saikosaponin d) were detected and tentatively identified. It was shown by our results that these compounds was metabolized to the forms of hydroxylation, glucuronidation, sulfation, glucuronidation with sulfation and glucuronidation with hydroxylation in vivo.

  17. Pattern recognition analysis of chromatographic fingerprints of Crocus sativus L. secondary metabolites towards source identification and quality control.

    Science.gov (United States)

    Aliakbarzadeh, Ghazaleh; Sereshti, Hassan; Parastar, Hadi

    2016-05-01

    Chromatographic fingerprinting is an effective methodology for authentication and quality control of herbal products. In the presented study, a chemometric strategy based on multivariate curve resolution-alternating least squares (MCR-ALS) and multivariate pattern recognition methods was used to establish a gas chromatography-mass spectrometry (GC-MS) fingerprint of saffron. For this purpose, the volatile metabolites of 17 Iranian saffron samples, collected from different geographical regions, were determined using the combined method of ultrasound-assisted solvent extraction (UASE) and dispersive liquid-liquid microextraction (DLLME), coupled with GC-MS. The resolved elution profiles and the related mass spectra obtained by an extended MCR-ALS algorithm were then used to estimate the relative concentrations and to identify the saffron volatile metabolites, respectively. Consequently, 77 compounds with high reversed match factors (RMFs > 850) were successfully determined. The relative concentrations of these compounds were used to generate a new data set which was analyzed by multivariate data analysis methods including principal component analysis (PCA) and k-means. Accordingly, the saffron samples were categorized into five classes using these techniques. The results revealed that 11 compounds, as biomarkers of saffron, contributed to the class discrimination and characterization. Eleven biomarkers including nine secondary metabolites of saffron (safranal, α- and β-isophorone, phenylethyl alcohol, ketoisophorone, 2,2,6-trimethyl-1,4-cyclohexanedione, 2,6,6-trimethyl-4-oxo-2-cyclohexen-1-carbaldehyde, 2,4,4-trimethyl-3-carboxaldehyde-5-hydroxy-2,5-cyclohexadien-1-one, and 2,6,6-trimethyl-4-hydroxy-1-cyclohexene-1-carboxaldehyde (HTCC)), a primary metabolite (linoleic acid), and a long chain fatty alcohol (nanocosanol) were distinguished as the saffron fingerprint. Finally, the individual contribution of each biomarker to the classes was determined by the

  18. Metabolism of BYZX in human liver microsomes and cytosol: identification of the metabolites and metabolic pathways of BYZX.

    Directory of Open Access Journals (Sweden)

    Lushan Yu

    Full Text Available BYZX, [(E-2-(4-((diethylaminomethylbenzylidene-5,6-dimethoxy-2,3-dihydroinden-one], belongs to a series of novel acetylcholinesterase inhibitors and has been synthesized as a new chemical entity for the treatment of Alzheimer's disease symptoms. When incubated with human liver microsomes (HLMs, BYZX was rapidly transformed into its metabolites M1, M2, and M3. The chemical structures of these metabolites were identified using liquid chromatography tandem mass spectrometry and nuclear magnetic resonance, which indicated that M1 was an N-desethylated and C = C hydrogenation metabolite of BYZX. M2 and M3 were 2 precursor metabolites, which resulted from the hydrogenation and desethylation of BYZX, respectively. Further studies with chemical inhibitors and human recombinant cytochrome P450s (CYPs, and correlation studies were performed. The results indicated that the N-desethylation of BYZX and M2 was mediated by CYP3A4 and CYP2C8. The reduced form of β-nicotinamide adenine dinucleotide 2'-phosphate was involved in the hydrogenation of BYZX and M3, and this reaction occurred in the HLMs and in the human liver cytosol. The hydrogenation reaction was not inhibited by any chemical inhibitors of CYPs, but it was significantly inhibited by some substrates of α,β-ketoalkene C = C reductases and their inhibitors such as benzylideneacetone, dicoumarol, and indomethacin. Our results suggest that α,β-ketoalkene C = C reductases may play a role in the hydrogenation reaction, but this issue requires further clarification.

  19. Using Nuclear Magnetic Resonance and MS/MS Spectroscopy for the Identification of Brodimoprim Metabolites in Rat Urine

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    Eight metabolites of brodimoprim (BDP) in rat urine were detected by NMR and ESI-MS/MS. They were demethyl-BDP glucuronide, demethyl-BDP sulfurate, demethyl-BDP glucuronide sulfurate, a-hydroxyl-BDP, a-hydroxyl-BDP glucuronide, BDP sulfurate, N-oxide-BDP sulfurate, and a-hydroxyl-N-oxide-BDP sulfurate. All the sulfurates are reported for the first time.

  20. Fisetin disposition and metabolism in mice: Identification of geraldol as an active metabolite. : Fisetin disposition and metabolism in mice

    OpenAIRE

    Touil, Yasmine; Auzeil, Nicolas; Boulinguez, François; Saighi, Hanane; Regazzetti, Anne; Scherman, Daniel; Chabot, Guy,

    2011-01-01

    International audience; Although the natural flavonoid fisetin (3,3',4',7-tetrahydroxyflavone) has been recently identified as an anticancer agent with antiangiogenic properties in mice, its in vivo pharmacokinetics and metabolism are presently not characterized. Our purpose was to determine the pharmacokinetics and metabolism of fisetin in mice and determine the biological activity of a detected fisetin metabolite. After fisetin administration of an efficacious dose of 223 mg/kg i.p. in mice...

  1. Fisetin disposition and metabolism in mice: Identification of geraldol as an active metabolite. : Fisetin disposition and metabolism in mice

    OpenAIRE

    Touil, Yasmine; Auzeil, Nicolas; Boulinguez, François; Saighi, Hanane; Regazzetti, Anne; Scherman, Daniel; Chabot, Guy

    2011-01-01

    International audience; Although the natural flavonoid fisetin (3,3',4',7-tetrahydroxyflavone) has been recently identified as an anticancer agent with antiangiogenic properties in mice, its in vivo pharmacokinetics and metabolism are presently not characterized. Our purpose was to determine the pharmacokinetics and metabolism of fisetin in mice and determine the biological activity of a detected fisetin metabolite. After fisetin administration of an efficacious dose of 223 mg/kg i.p. in mice...

  2. [Identification of metabolites of epiberberine in rat liver microsomes and its inhibiting effects on CYP2D6].

    Science.gov (United States)

    Yang, Xiao-Yan; Ye, Jing; Sun, Gui-Xia; Xue, Bao-Juan; Zhao, Yuan-Yuan; Miao, Pei-Pei; Su, Jin; Zhang, Yu-Jie

    2014-10-01

    Epiberberine, one of the most important isoquinoline alkaloid in Coptidis Rhizoma, possesses extensive pharmacological activities. In this paper, the liquid chromatography-tandem mass spectrometry (LC-MS/MS) was used to study phase I and phase II metabolites. A Thermo HPLC system (including Surveyor AS, Surveyor LC Pump, Surveyor PDA. USA) was used. The cocktail probe drugs method was imposed to determine the content change of metoprolol, dapsone, phenacetin, chlorzoxazone and tolbutamide simultaneously for evaluating the activity of CYP2D6, CYP3A4, CYP1A2, CYP2E1 and CYP2C9 under different concentrations of epiberberine in rat liver microsomes. The result showed that epiberberine may have phase I and phase II metabolism in the rat liver and two metabolites in phase I and three metabolites in phase II are identified in the temperature incubation system of in vitro liver microsomes. Epiberberine showed significant inhibition on CYP2D6 with IC50 value of 35.22 μmol L(-1), but had no obvious inhibiting effect on the activities of CYP3A4, CYP1A2, CYP2E1 and CYP2C9. The results indicated that epiberberine may be caused drug interactions based on CYP2D6 enzyme. This study aims to provide a reliable experimental basis for its further research and development of epiberberine.

  3. Screening, identification, optimization of fermentation conditions, and extraction of secondary metabolites for the biocontrol of Rhizoctonia Solani AG-3

    Directory of Open Access Journals (Sweden)

    Taswar Ahsan

    2017-01-01

    Full Text Available In this study a strain of Streptomyces sp. was isolated from soil and identified by 16S rRNA gene sequencing technology. The strain was screened for antibiotics production effective against biocontrol of Rhizoctonia solani AG-3 to cure the target spot disease in tobacco. For enhance production of secondary metabolites, central composite design of response surface methodology (RSM was applied in submerged fermentation. The maximum metabolite production was using medium volume of 55 mL in 250 mL flask, agitation speed of 165 rpm, incubation temperature 30 °C, initial medium pH of 6.8 and inoculum size of 7%. Solvent extraction method was used to extract the secondary metabolites and active compounds were purified by silica gel column chromatography. The purified fractions were further investigated by gas chromatography-mass spectrophotometer (GC-MS. GC-MS analysis showed 48 compounds, among them 12 were active against pathogen. These findings indicated that the strain Streptomyces TA 1123 was a potential antagonist against R. solani AG-3.

  4. Transformation of tamoxifen and its major metabolites during water chlorination: Identification and in silico toxicity assessment of their disinfection byproducts.

    Science.gov (United States)

    Negreira, Noelia; Regueiro, Jorge; López de Alda, Miren; Barceló, Damià

    2015-11-15

    The selective estrogen receptor modulator tamoxifen is the most commonly used drug for the treatment and prevention of breast cancer. Tamoxifen is considered as a pro-drug since it is known to exert its pharmacological effect through its major active metabolites, 4-hydroxy-tamoxifen and 4-hydroxy-N-desmethyl-tamoxifen, which are mainly excreted in the urine in the days following administration. In the present work, the reactivity of tamoxifen and its major active metabolites in free chlorine-containing water was investigated for the first time. Under the studied chlorination conditions, tamoxifen was fairly stable whereas its metabolites were quickly degraded. A total of thirteen chlorinated byproducts were tentatively identified by ultra-high performance liquid chromatography coupled to high-resolution hybrid quadrupole-Orbitrap tandem mass spectrometry. Time-course profiles of the identified byproducts were followed in real wastewater samples under conditions that simulate wastewater disinfection. A preliminary assessment of their acute aquatic toxicity at two trophic levels by means of quantitative structure-activity relationship models showed that the identified byproducts were up to 110-fold more toxic than the parent compounds.

  5. Dose-Independent ADME Properties and Tentative Identification of Metabolites of α-Mangostin from Garcinia mangostana in Mice by Automated Microsampling and UPLC-MS/MS Methods.

    Science.gov (United States)

    Han, Seung Yon; You, Byoung Hoon; Kim, Yu Chul; Chin, Young-Won; Choi, Young Hee

    2015-01-01

    The information about a marker compound's pharmacokinetics in herbal products including the characteristics of absorption, distribution, metabolism, excretion (ADME) is closely related to the efficacy/toxicity. Also dose range and administration route are critical factors to determine the ADME profiles. Since the supply of a sufficient amount of a marker compound in in vivo study is still difficult, pharmacokinetic investigations which overcome the limit of blood collection in mice are desirable. Thus, we have attempted to investigate concurrently the ADME and proposed metabolite identification of α-mangostin, a major constituent of mangosteen, Garcinia mangostana L, in mice with a wide dose range using an in vitro as well as in vivo automated micro-sampling system together. α-mangostin showed dose-proportional pharmacokinetics at intravenous doses of 5-20 mg/kg and oral doses of 10-100 mg/kg. The gastrointestinal absorption of α-mangostin was poor and the distribution of α-mangostin was relatively high in the liver, intestine, kidney, fat, and lung. α-mangostin was extensively metabolized in the liver and intestine. With regards to the formation of metabolites, the glucuronidated, bis-glucuronidated, dehydrogenated, hydrogenated, oxidized, and methylated α-mangostins were tentatively identified. We suggest that these dose-independent pharmacokinetic characteristics of α-mangostin in mice provide an important basis for preclinical applications of α-mangostin as well as mangosteen. In addition, these experimental methods can be applied to evaluate the pharmacokinetics of natural products in mice.

  6. Using silver and bighead carp cell lines for the identification of a unique metabolite fingerprint from thiram-specific chemical exposure

    Science.gov (United States)

    Putnam, Joel G.; Nelson, Justine; Leis, Eric M; Erickson, Richard A.; Hubert, Terrance D.; Amberg, Jon J.

    2017-01-01

    Conservation biology often requires the control of invasive species. One method is the development and use of biocides. Identifying new chemicals as part of the biocide registration approval process can require screening millions of compounds. Traditionally, screening new chemicals has been done in vivo using test organisms. Using in vitro (e.g., cell lines) and in silico (e.g., computer models) methods decrease test organism requirements and increase screening speed and efficiency. These methods, however, would be greatly improved by better understanding how individual fish species metabolize selected compounds.We combined cell assays and metabolomics to create a powerful tool to facilitate the identification of new control chemicals. Specifically, we exposed cell lines established from bighead carp and silver carp larvae to thiram (7 concentrations) then completed metabolite profiling to assess the dose-response of the bighead carp and silver carp metabolome to thiram. Forty one of the 700 metabolomic markers identified in bighead carp exhibited a dose-response to thiram exposure compared to silver carp in which 205 of 1590 metabolomic markers exhibited a dose-response. Additionally, we identified 11 statistically significant metabolomic markers based upon volcano plot analysis common between both species. This smaller subset of metabolites formed a thiram-specific metabolomic fingerprint which allowed for the creation of a toxicant specific, rather than a species-specific, metabolomic fingerprint. Metabolomic fingerprints may be used in biocide development and improve our understanding of ecologically significant events, such as mass fish kills.

  7. Using silver and bighead carp cell lines for the identification of a unique metabolite fingerprint from thiram-specific chemical exposure.

    Science.gov (United States)

    Putnam, Joel G; Nelson, Justine E; Leis, Eric M; Erickson, Richard A; Hubert, Terrance D; Amberg, Jon J

    2017-02-01

    Conservation biology often requires the control of invasive species. One method is the development and use of biocides. Identifying new chemicals as part of the biocide registration approval process can require screening millions of compounds. Traditionally, screening new chemicals has been done in vivo using test organisms. Using in vitro (e.g., cell lines) and in silico (e.g., computer models) methods decrease test organism requirements and increase screening speed and efficiency. These methods, however, would be greatly improved by better understanding how individual fish species metabolize selected compounds. We combined cell assays and metabolomics to create a powerful tool to facilitate the identification of new control chemicals. Specifically, we exposed cell lines established from bighead carp and silver carp larvae to thiram (7 concentrations) then completed metabolite profiling to assess the dose-response of the bighead carp and silver carp metabolome to thiram. Forty one of the 700 metabolomic markers identified in bighead carp exhibited a dose-response to thiram exposure compared to silver carp in which 205 of 1590 metabolomic markers exhibited a dose-response. Additionally, we identified 11 statistically significant metabolomic markers based upon volcano plot analysis common between both species. This smaller subset of metabolites formed a thiram-specific metabolomic fingerprint which allowed for the creation of a toxicant specific, rather than a species-specific, metabolomic fingerprint. Metabolomic fingerprints may be used in biocide development and improve our understanding of ecologically significant events, such as mass fish kills.

  8. Metabolite identification of a radiotracer by electrochemistry coupled to liquid chromatography with mass spectrometric and radioactivity detection.

    Science.gov (United States)

    Baumann, Anne; Faust, Andreas; Law, Marylin P; Kuhlmann, Michael T; Kopka, Klaus; Schäfers, Michael; Karst, Uwe

    2011-07-01

    Radioligands, which specifically bind to a receptor or enzyme (target), enable molecular imaging of the target expression by positron emission tomography (PET). One very promising PET tracer is (S)-1-(4-(2-[(18)F]-fluoroethoxy)benzyl)-5-[1-(2-methoxymethylpyrrolidinyl)sulfonyl]isatin (isatin), a caspase-3 inhibitor, which has been developed at the University Hospital of Münster to image cell death (apoptosis). The translation of this novel tracer from preclinical evaluation to clinical examinations requires biodistribution studies, which characterize the pharmakodynamics and metabolic fate of the compound. This information is used to further optimize the radioligands and to interpret radioactive signals from tissues upon injection of the radioligand in vivo with respect to their specificity. The analysis of the metabolism of radioligands is hampered by the low amount of the compound being typically injected (nano/picomolar amount per injection). In the present study, electrochemistry (EC) is applied to elucidate the oxidative metabolism pathway of the radiotracer. Previous studies have demonstrated that EC can be utilized as a complementary tool to conventional in vitro approaches in drug metabolism studies. Thereby, potential oxidative metabolites of the isatin are determined by EC coupled to electrospray ionization mass spectrometry (EC/ESI-MS). Moreover, using EC/liquid chromatography (LC) and ESI-ion trap MS(n), structural elucidation of the oxidation products is performed. Comparatively to EC, in vitro metabolism studies with rat liver microsomes are conducted. Finally, the developed LC/ESI-MS method is applied to determine metabolites in body fluids and cell extracts from in vivo studies with the nonradioactive ((19)F) and radioactive isatin ((18)F). On the basis of the electrochemically generated oxidation products of the radioligand, the major radioactive metabolite occurring in vivo was successfully identified.

  9. Identification of Minor Secondary Metabolites from the Latex of Croton lechleri (Muell-Arg) and Evaluation of Their Antioxidant Activity

    OpenAIRE

    Maria Iorizzi; Francesco Visioli; Gelsomina Fico; Sara Vitalini; Franco Zollo; Fulvio Gala; Simona De Marino

    2008-01-01

    Dragon’s blood (Sangre de drago), a viscous red sap derived from Croton lechleri Muell-Arg (Euphorbiaceae), is extensively used by indigenous cultures of the Amazonian basin for its wound healing properties. The aim of this study was to identify the minor secondary metabolites and test the antioxidant activity of this sustance. A bioguided fractionation of the n-hexane, chloroform, n-butanol, and aqueous extracts led to the isolation of 15 compounds: three megastigmanes, four flavan-3-ol...

  10. Identification of Three New N-Demethylated and O-Demethyled Bisbenzylisoquinoline Alkaloid Metabolites of Isoliensinine from Dog Hepatic Microsomes

    Directory of Open Access Journals (Sweden)

    Su Zeng

    2012-10-01

    Full Text Available Isoliensinine, a natural phenolic bisbenzyltetrahydroisoquinoline alkaloid, has received considerable attention for its potential biological effects such as antioxidant and anti-HIV activities. From the dog hepatic microsomes of isoliensinine, three new N-demethylated and O-demethylated metabolites, 2-N-desmethyl-isoliensinine (M1, 2'-N-desmethylisoliensinine (M2, and 2'-N-6-O-didesmethylisoliensinine (M3, were identified by high-performance liquid chromatography and data-dependent electrospray ionization tandem mass spectrometry. Possible metabolic pathways for isoliensinine have been proposed. The result should prove very helpful for evaluation of the drug-like properties of isoliensinine and other bisbenzylisoquinoline alkaloids.

  11. Pipeline integrity: ILI baseline data for QRA

    Energy Technology Data Exchange (ETDEWEB)

    Porter, Todd R. [Tuboscope Pipeline Services, Houston, TX (United States)]. E-mail: tporter@varco.com; Silva, Jose Augusto Pereira da [Pipeway Engenharia, Rio de Janeiro, RJ (Brazil)]. E-mail: guto@pipeway.com; Marr, James [MARR and Associates, Calgary, AB (Canada)]. E-mail: jmarr@marr-associates.com

    2003-07-01

    The initial phase of a pipeline integrity management program (IMP) is conducting a baseline assessment of the pipeline system and segments as part of Quantitative Risk Assessment (QRA). This gives the operator's integrity team the opportunity to identify critical areas and deficiencies in the protection, maintenance, and mitigation strategies. As a part of data gathering and integration of a wide variety of sources, in-line inspection (ILI) data is a key element. In order to move forward in the integrity program development and execution, the baseline geometry of the pipeline must be determined with accuracy and confidence. From this, all subsequent analysis and conclusions will be derived. Tuboscope Pipeline Services (TPS), in conjunction with Pipeway Engenharia of Brazil, operate ILI inertial navigation system (INS) and Caliper geometry tools, to address this integrity requirement. This INS and Caliper ILI tool data provides pipeline trajectory at centimeter level resolution and sub-metre 3D position accuracy along with internal geometry - ovality, dents, misalignment, and wrinkle/buckle characterization. Global strain can be derived from precise INS curvature measurements and departure from the initial pipeline state. Accurate pipeline elevation profile data is essential in the identification of sag/over bend sections for fluid dynamic and hydrostatic calculations. This data, along with pipeline construction, operations, direct assessment and maintenance data is integrated in LinaViewPRO{sup TM}, a pipeline data management system for decision support functions, and subsequent QRA operations. This technology provides the baseline for an informed, accurate and confident integrity management program. This paper/presentation will detail these aspects of an effective IMP, and experience will be presented, showing the benefits for liquid and gas pipeline systems. (author)

  12. Identification of gene-specific polymorphisms and association with capsaicin pathway metabolites in Capsicum annuum L. collections.

    Science.gov (United States)

    Reddy, Umesh K; Almeida, Aldo; Abburi, Venkata L; Alaparthi, Suresh Babu; Unselt, Desiree; Hankins, Gerald; Park, Minkyu; Choi, Doil; Nimmakayala, Padma

    2014-01-01

    Pepper (Capsicum annuum L.) is an economically important crop with added nutritional value. Production of capsaicin is an important quantitative trait with high environmental variance, so the development of markers regulating capsaicinoid accumulation is important for pepper breeding programs. In this study, we performed association mapping at the gene level to identify single nucleotide polymorphisms (SNPs) associated with capsaicin pathway metabolites in a diverse Capsicum annuum collection during two seasons. The genes Pun1, CCR, KAS and HCT were sequenced and matched with the whole-genome sequence draft of pepper to identify SNP locations and for further characterization. The identified SNPs for each gene underwent candidate gene association mapping. Association mapping results revealed Pun1 as a key regulator of major metabolites in the capsaicin pathway mainly affecting capsaicinoids and precursors for acyl moieties of capsaicinoids. Six different SNPs in the promoter sequence of Pun1 were found associated with capsaicin in plants from both seasons. Our results support that CCR is an important control point for the flux of p-coumaric acid to specific biosynthesis pathways. KAS was found to regulate the major precursors for acyl moieties of capsaicinoids and may play a key role in capsaicinoid production. Candidate gene association mapping of Pun1 suggested that the accumulation of capsaicinoids depends on the expression of Pun1, as revealed by the most important associated SNPs found in the promoter region of Pun1.

  13. Identification of Taxus cuspidata Sieb. et Zucc. endophytic fungi-new species, species known and their metabolite

    Institute of Scientific and Technical Information of China (English)

    XlANGYong; LUAn-guo; WUWen-fang

    2003-01-01

    A total of 94 isolates of endophytic fungi were isolated from the bark of 200-yr.-old Taxus cuspidata Sieb. et Zucc.in the primeval forest of the Changbai Mountain Natural Reserve, and 19 species of endophytic fungi were identified, including 10 new recorded-genus-species, 2 new species (Phomopsis Iongiscoleosporu Y. Xiang et Lu An Guo Wu Wen Fang, Coniothyrium macrospoum Y. Xiang J.X. et Lu An Guo Wu Wen Fang), 1 new varied species (Alternaria alternata (Fr.) Keissler var. taxi Y.Xiang et Lu An Guo) and 6 known species of China (Eurotium amstelodomi Mgngin, Eurotium repens de Bary, Botrytis sp.,Penicillium citrinum Thom, Epicoccum nigrium LinK, Fusarium sp.). Through thin layer chromatography (TLC), liquid fermentation metabolite of the strains was determined, and four strains (Alternaria alternata (Fr.) Keissler var. taxi Y. Xiang et Lu An Guo Wu Wen Fang, Botrytis sp., Eurotium amsteloodomi Mgngin, Eurotium repens de Bary) were screened out, whose metabolites reacted positively with the vanillic aldehyde that was one special taxoid developer. Among the four strains, Alternaria alternata (Fr.) Keissler var. taxi Y. Xiang et Lu An Guo, produced one compound largely, which positively reacted with one alkaloids developer-Bismuth potassium iodide. The compound is identified as taxoids type through spectrum analysis. This demonstrates that Alternaria alternata (Fr.) Keissler var. taxiY. Xiang et Lu An Guo can highly produce taxoids largely.

  14. Degradation Kinetics of 6‴-p-Coumaroylspinosin and Identification of Its Metabolites by Rat Intestinal Flora.

    Science.gov (United States)

    Jiao, Lijuan; Li, Yaxin; Zhang, Yanqing; Liu, Junjun; Xie, Junbo; Zhang, Kunsheng; Zhou, Aimin

    2017-06-07

    6‴-p-Coumaroylspinosin (P-CS), a bioactive flavonoid, is typically extracted from Semen Ziziphi Spinosae (SZS). In this study, a high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method was developed to determine P-CS for investigating the degradation characteristics of P-CS incubated with rat feces. The results showed that P-CS degraded rapidly and the degradation speeds varied depending upon the P-CS concentrations (3, 15, and 30 μg/mL). The degradation of P-CS processes follow first-order kinetics. On the basis of the mass spectrometry (MS) spectrum mode of the product ions, two main metabolites of P-CS were identified. Swertisin was the main metabolite at 3 and 15 μg/mL, while spinosin was produced when the P-CS concentration was 30 μg/mL. Spinosin and swertisin could improve mRNA transcription levels of glutamate receptor K1, K2, and K3 (GluK1, GluK2, and GluK3) subunits in rat hippocampal neurons. In addition, they showed an obvious synergistic effect in this respect. Collectively, the results can be used to explain the metabolic and pharmacological mechanisms of P-CS.

  15. Effectiveness of different solid-phase microextraction fibres for differentiation of selected Madeira island fruits based on their volatile metabolite profile--identification of novel compounds.

    Science.gov (United States)

    Pereira, João; Pereira, Jorge; Câmara, José S

    2011-01-15

    A headspace solid-phase microextraction (HS-SPME) procedure based on five commercialised fibres (85 μm polyacrylate - PA, 100 μm polydimethylsiloxane - PDMS, 65 μm polydimethylsiloxane/divinylbenzene - PDMS/DVB, 70 μm carbowax/divinylbenzene - CW/DVB and 85 μm carboxen/polydimethylsiloxane - CAR/PDMS) is presented for the characterization of the volatile metabolite profile of four selected Madeira island fruit species, lemon (Citrus limon), kiwi (Actinidia deliciosa), papaya (Carica papaya L.) and Chickasaw plum (Prunus angustifolia). The isolation of metabolites was followed by thermal desorption gas chromatography-quadrupole mass spectrometry (GC-qMS) methodology. The performance of the target fibres was evaluated and compared. The SPME fibre coated with CW/DVB afforded the highest extraction efficiency in kiwi and papaya pulps, while in lemon and plum the same was achieved with PMDS/DVB fibre. This procedure allowed for the identification of 80 compounds, 41 in kiwi, 24 in plums, 23 in papaya and 20 in lemon. Considering the best extraction conditions, the most abundant volatiles identified in kiwi were the intense aldehydes and ethyl esters such as (E)-2-hexenal and ethyl butyrate, while in Chicasaw plum predominate 2-hexenal, 2-methyl-4-pentenal, hexanal, (Z)-3-hexenol and cyclohexylene oxide. The major compounds identified in the papaya pulp were benzyl isothiocyanate, linalool oxide, furfural, hydroxypropanone, linalool and acetic acid. Finally, lemon was shown to be the most divergent of the four fruits, being its aroma profile composed almost exclusively by terpens, namely limonene, γ-terpinene, o-cymene and α-terpinolene. Thirty two volatiles were identified for the first time in the fruit or close related species analysed and 14 volatiles are reported as novel volatile metabolites in fruits. This includes 5 new compounds in kiwi (2-cyclohexene-1,4-dione, furyl hydroxymethyl ketone, 4-hydroxydihydro-2(3H)-furanone, 5-acetoxymethyl-2-furaldehyde and

  16. Understanding and classifying metabolite space and metabolite-likeness.

    Directory of Open Access Journals (Sweden)

    Julio E Peironcely

    -likeness of candidate molecules during metabolite identification in the metabolomics field.

  17. 32P-postlabelling analysis of dibenz[a,j]acridine-DNA adducts in mice: identification of proximate metabolites.

    Science.gov (United States)

    Talaska, G; Roh, J; Schamer, M; Reilman, R; Xue, W; Warshawsky, D

    1995-03-30

    N-Heterocyclic polynuclear aromatics are widely-occurring environmental pollutants formed during the pyrolysis of nitrogen-containing organic chemicals. Dibenz[a,j]acridine (DBA), a member of this class, has been shown to be a skin carcinogen in mice. We undertook studies to determine the organ distribution of DBA-DNA adducts and to identify the DBA metabolites which lead to the formation of carcinogen-DNA adducts in vivo. DBA and its metabolites, trans-DBA-1,2-dihydrodiol (DBA-1,2-DHD) trans-DBA-3,4-dihydrodiol (DBA-3,4-DHD) and trans-DBA-5,6-dihydrodiol (DBA-5,6-DHD), were topically applied on mice. DNA was isolated using enzyme-solvent extraction methods, and analyzed for carcinogen-DNA adducts using 32P-postlabelling. In skin, DBA produced two distinct adducts (Adducts 1 and 2). The same two adducts were seen when DBA-3,4-DHD was applied. In addition, the total adduct level elicited by DBA-3,4-DHD was twice that of the parent compound. Two adducts (Adducts 3 and 4) were also seen in mouse skin when DBA-5,6-DHD was applied, but these differed chromatographically from adducts seen with DBA. However, when DBA-3,4-DHD was applied and analyzed using sensitive nuclease P1 32P-postlabelling, all four adducts could be detected. These results suggest that the major route of DBA activation to DNA-binding species in skin is through formation of DBA-3,4-DHD and subsequent metabolism of this compound to a bay-region diol-epoxide. However, we postulate that another activation pathway may proceed through a bis-dihydrodiol-epoxide.

  18. Degradation of fluoroquinolone antibiotics and identification of metabolites/transformation products by liquid chromatography-tandem mass spectrometry.

    Science.gov (United States)

    Maia, Alexandra S; Ribeiro, Ana R; Amorim, Catarina L; Barreiro, Juliana C; Cass, Quezia B; Castro, Paula M L; Tiritan, Maria Elizabeth

    2014-03-14

    Antibiotics are a therapeutic class widely found in environmental matrices and extensively studied due to its persistence and implications for multi-resistant bacteria development. This work presents an integrated approach of analytical multi-techniques on assessing biodegradation of fluorinated antibiotics at a laboratory-scale microcosmos to follow removal and formation of intermediate compounds. Degradation of four fluoroquinolone antibiotics, namely Ofloxacin (OFL), Norfloxacin (NOR), Ciprofloxacin (CPF) and Moxifloxacin (MOX), at 10 mg L(-1) using a mixed bacterial culture, was assessed for 60 days. The assays were followed by a developed and validated analytical method of LC with fluorescence detection (LC-FD) using a Luna Pentafluorophenyl (2) 3 μm column. The validated method demonstrated good selectivity, linearity (r(2)>0.999), intra-day and inter-day precisions (RSD<2.74%) and accuracy. The quantification limits were 5 μg L(-1) for OFL, NOR and CPF and 20 μg L(-1) for MOX. The optimized conditions allowed picturing metabolites/transformation products formation and accumulation during the process, stating an incomplete mineralization, also shown by fluoride release. OFL and MOX presented the highest (98.3%) and the lowest (80.5%) extent of degradation after 19 days of assay, respectively. A representative number of samples was selected and analyzed by LC-MS/MS with triple quadrupole and the molecular formulas were confirmed by a quadruple time of flight analyzer (QqTOF). Most of the intermediates were already described as biodegradation and/or photodegradation products in different conditions; however unknown metabolites were also identified. The microbial consortium, even when exposed to high levels of FQ, presented high percentages of degradation, never reported before for these compounds. Copyright © 2014 Elsevier B.V. All rights reserved.

  19. Common Data Analysis Pipeline | Office of Cancer Clinical Proteomics Research

    Science.gov (United States)

    CPTAC supports analyses of the mass spectrometry raw data (mapping of spectra to peptide sequences and protein identification) for the public using a Common Data Analysis Pipeline (CDAP). The data types available on the public portal are described below. A general overview of this pipeline can be downloaded here. Mass Spectrometry Data Formats RAW (Vendor) Format

  20. Trace Software Pipelining

    Institute of Scientific and Technical Information of China (English)

    王剑; AndreasKrall; 等

    1995-01-01

    Global software pipelining is a complex but efficient compilation technique to exploit instruction-level parallelism for loops with branches.This paper presents a novel global software pipelining technique,called Trace Software Pipelining,targeted to the instruction-level parallel processors such as Very Long Instruction Word (VLIW) and superscalar machines.Trace software pipelining applies a global code scheduling technique to compact the original loop body.The resulting loop is called a trace software pipelined (TSP) code.The trace softwrae pipelined code can be directly executed with special architectural support or can be transformed into a globally software pipelined loop for the current VLIW and superscalar processors.Thus,exploiting parallelism across all iterations of a loop can be completed through compacting the original loop body with any global code scheduling technique.This makes our new technique very promising in practical compilers.Finally,we also present the preliminary experimental results to support our new approach.

  1. Identification of in vivo and in vitro metabolites of 4,5-dimethoxycanthin-6-one by HPLC-Q-TOF-MS/MS.

    Science.gov (United States)

    Miao, Xiaolei; Wang, Junjun; Chen, Liang; Peng, Zhihong; Chen, Yong

    2016-05-01

    4,5-Dimthexycanthin-6-one and 5-hydroxy-4-methoxycanthin-6-one are the main active ingredients of Picrasma quassioides, which is a widely used herbal medicine for the treatment of gastroenteritis, snakebite, infection and hypertension in China. In the present study, the in vitro metabolites of 4,5-dimethoxycanthin-6-one in rat, mouse, dog and human liver microsomes, as well as the in vivo metabolites in rat plasma and urine following a single oral dose of 4,5-dimethoxycanthin-6-one, were identified by high-performance liquid chromatography combined with triple TOF mass spectrometry (HPLC-TOF/MS/MS). The metabolites were elucidated based on an accurate mass measurement, the MS/MS fragmentation patterns, the retention times of the parent drug and its metabolites, and the relevant drug biotransformation rules. After incubation in liver mcrosomes for 50 min, 4,5-dimethoxycanthin-6-one produced 8 phase I metabolites including 2 mono-demethylated metabolites (M1, M2), 3 mono-hydroxylated metabolites (M3-M5), and 3 mono-demethylated and mono-hydroxylated metabolites (M6-M8) in rat and mouse liver microsomes, 7 phase I metabolites (without M7) in dog and human liver microsomes. After a single oral administration of 4,5-dimethoxycanthin-6-one to rats, there were 3 phase I metabolites (M1, M2 and M5) detected in rat plasma and 5 phase I metabolites (M1-M5) in rat urine. Phase II metabolites were not detected in rat plasma and urine. Among these metabolites, mono-demethylated metabolites (M1 and M2) were the major metabolites of 4,5-dimethoxycanthin-6-one, mono-hydroxylated metabolites (M3-M5) were the minor metabolites of 4,5-dimethoxycanthin-6-one.

  2. Dose-Independent ADME Properties and Tentative Identification of Metabolites of α-Mangostin from Garcinia mangostana in Mice by Automated Microsampling and UPLC-MS/MS Methods.

    Directory of Open Access Journals (Sweden)

    Seung Yon Han

    Full Text Available The information about a marker compound's pharmacokinetics in herbal products including the characteristics of absorption, distribution, metabolism, excretion (ADME is closely related to the efficacy/toxicity. Also dose range and administration route are critical factors to determine the ADME profiles. Since the supply of a sufficient amount of a marker compound in in vivo study is still difficult, pharmacokinetic investigations which overcome the limit of blood collection in mice are desirable. Thus, we have attempted to investigate concurrently the ADME and proposed metabolite identification of α-mangostin, a major constituent of mangosteen, Garcinia mangostana L, in mice with a wide dose range using an in vitro as well as in vivo automated micro-sampling system together. α-mangostin showed dose-proportional pharmacokinetics at intravenous doses of 5-20 mg/kg and oral doses of 10-100 mg/kg. The gastrointestinal absorption of α-mangostin was poor and the distribution of α-mangostin was relatively high in the liver, intestine, kidney, fat, and lung. α-mangostin was extensively metabolized in the liver and intestine. With regards to the formation of metabolites, the glucuronidated, bis-glucuronidated, dehydrogenated, hydrogenated, oxidized, and methylated α-mangostins were tentatively identified. We suggest that these dose-independent pharmacokinetic characteristics of α-mangostin in mice provide an important basis for preclinical applications of α-mangostin as well as mangosteen. In addition, these experimental methods can be applied to evaluate the pharmacokinetics of natural products in mice.

  3. Polyamine metabolism in ripening tomato fruit. I. Identification of metabolites of putrescine and spermidine. [Lycopersicon esculentum Mill

    Energy Technology Data Exchange (ETDEWEB)

    Rastogi, R.; Davies, P.J. (Cornell Univ., Ithaca, NY (USA))

    1990-11-01

    The metabolism of (1,4-{sup 14}C)putrescine and (terminal methylene-{sup 3}H)spermidine was studied in the fruit pericarp (breaker stage) discs of tomato (Lycopersicon esculentum Mill.) cv Rutgers, and the metabolites identified by high performance liquid chromatography and gas chromatography-mass spectrometry. The metabolism of both putrescine and spermidine was relatively slow; in 24 hours about 15% of each amine was metabolized. The {sup 14}C label from putrescine was incorporated into spermidine, {gamma}-aminobutyric acid (GABA), glutamic acid, and a polar fraction eluting with sugars and organic acids. In the presence of gabaculine, a specific inhibitor of GABA:pyruvate transminase, the label going into glutamic acid, sugars and organic acids decreased by 80% while that in GABA increased about twofold, indicating that the transamination reaction is probably a major fate of GABA produced from putrescine in vivo. ({sup 3}H)Spermidine was catabolized into putrescine and {beta}-alanine. The conversion of putrescine into GABA, and that of spermidine into putrescine, suggests the presence of polyamine oxidizing enzymes in tomato pericarp tissues. The possible pathways of putrescine and spermidine metabolism are discussed.

  4. Pathway Analysis and Metabolites Identification by Metabolomics of Etiolation Substrate from Fresh-Cut Chinese Water Chestnut (Eleocharis tuberosa

    Directory of Open Access Journals (Sweden)

    Yi-Xiao Li

    2016-12-01

    Full Text Available Fresh-cut Chinese water chestnuts (CWC turn yellow after being peeled, reducing their shelf life and commercial value. Metabolomics, the systematic study of the full complement of small molecular metabolites, was useful for clarifying the mechanism of fresh-cut CWC etiolation and developing methods to inhibit yellowing. In this study, metabolic alterations associated with etiolation at different growth stages (0 day, 2 days, 3 days, 4 days, 5 days from fresh-cut CWC were investigated using LC–MS and analyzed by pattern recognition methods (principal component analysis (PCA, partial least squares-discriminant analysis (PLS-DA, and orthogonal projection to latent structures-discriminant analysis (OPLS-DA. The metabolic pathways of the etiolation molecules were elucidated. The main metabolic pathway appears to be the conversion of phenylalanine to p-coumaroyl-CoA, followed by conversion to naringenin chalcone, to naringenin, and naringenin then following different pathways. Firstly, it can transform into apigenin and its derivatives; secondly, it can produce eriodictyol and its derivatives; and thirdly it can produce dihydrokaempferol, quercetin, and myricetin. The eriodictyol can be further transformed to luteolin, cyanidin, dihydroquercetin, dihydrotricetin, and others. This is the first reported use of metabolomics to study the metabolic pathways of the etiolation of fresh-cut CWC.

  5. Pathway Analysis and Metabolites Identification by Metabolomics of Etiolation Substrate from Fresh-Cut Chinese Water Chestnut (Eleocharis tuberosa).

    Science.gov (United States)

    Li, Yi-Xiao; Pan, Yong-Gui; He, Feng-Ping; Yuan, Meng-Qi; Li, Shang-Bin

    2016-12-01

    Fresh-cut Chinese water chestnuts (CWC) turn yellow after being peeled, reducing their shelf life and commercial value. Metabolomics, the systematic study of the full complement of small molecular metabolites, was useful for clarifying the mechanism of fresh-cut CWC etiolation and developing methods to inhibit yellowing. In this study, metabolic alterations associated with etiolation at different growth stages (0 day, 2 days, 3 days, 4 days, 5 days) from fresh-cut CWC were investigated using LC-MS and analyzed by pattern recognition methods (principal component analysis (PCA), partial least squares-discriminant analysis (PLS-DA), and orthogonal projection to latent structures-discriminant analysis (OPLS-DA)). The metabolic pathways of the etiolation molecules were elucidated. The main metabolic pathway appears to be the conversion of phenylalanine to p-coumaroyl-CoA, followed by conversion to naringenin chalcone, to naringenin, and naringenin then following different pathways. Firstly, it can transform into apigenin and its derivatives; secondly, it can produce eriodictyol and its derivatives; and thirdly it can produce dihydrokaempferol, quercetin, and myricetin. The eriodictyol can be further transformed to luteolin, cyanidin, dihydroquercetin, dihydrotricetin, and others. This is the first reported use of metabolomics to study the metabolic pathways of the etiolation of fresh-cut CWC.

  6. Identification of antibacterial secondary metabolite from marine Streptomyces sp. VITBRK4 and its activity against drug resistant Gram positive bacteria

    Directory of Open Access Journals (Sweden)

    Benita Mercy R

    2013-12-01

    Full Text Available Drug resistance by bacterial pathogens becomes a major health problem worldwide. Hence, it is important to search for broad spectrum of antibiotic from natural sources. Marine actinomycetes isolated from marine sediments collected at different sampling sites along the southeast coast of Bay of Bengal, India were investigated for antagonistic activity against selected drug resistant Gram positivebacterial pathogens. All actinomycetes isolates were screened for antibacterial activity against standard drug resistant ATCC strains. The potential isolate which showed higher inhibitory activity against drug resistant pathogens was mass cultured and the ethyl acetate (EA extract of the cell free culture broth was tested for antibacterial activity. The biochemical, morphological and physiological characterisation of the isolate revealed that it was Gram-positive rod, sporulating and produced grey aerial mycelium. The spore chain morphology, and smooth surface morphology showed that it belongs to the genus Streptomyces.Based on Nonomura’s key for classification of Streptomycesand Bergey’s Manual of Determinative Bacteriology, the isolatewas identified as Streptomyces species and designated as Streptomyces sp. VITBRK4.Purification and characterization of EA extract of the isolate by thin layer chromatography (TLC and HPLC-DAD analysis showed the presence of indolo compound along with few other unidentified metabolites. The result of this study showed that the antibacterial activity of the EA extract against drug resistant strains may be due to indolo compound present in the extract.

  7. Green pipeline dreams; Gruene Pipeline-Traeume

    Energy Technology Data Exchange (ETDEWEB)

    Wiedemann, Karsten

    2010-11-15

    In theory, Germany and the other EU states would be able to cover their natural gas demand completely with pipeline-supplied biomethane. But will this be really possible in practice? The contribution takes a closer look. (orig.)

  8. Ultrasound monitoring of pipelines; Ultraschallueberwachung an Pipelines

    Energy Technology Data Exchange (ETDEWEB)

    Kircher, W.; Skerra, B.; Kobitsch-Meyer, S. [SONOTEC Ultraschallsensorik, Halle GmbH (Germany)

    2007-01-15

    Pipelines are the most modern, effective and safest transport system, which is world widely spread in a network of millions km length and is annually enlarged about thousands of km. It is sure that these systems, if they should stay save and effective, must be maintained adequately. A technique, which provides accurate and reliable measurement data without interrupting the pipeline operation, ''through the wall'', is the ultrasonic technology. This non-intrusive technology provides data for pig detection as well as it is used for recognising products in pipelines, detecting levels or full/empty states and accomplishment of sediment measurement, distance measurements, position detections and leak search. The article gives a review and describes some applications of ultrasonic technology in pipeline technique. (orig.)

  9. ALMA Pipeline: Current Status

    Science.gov (United States)

    Shinnaga, H.; Humphreys, E.; Indebetouw, R.; Villard, E.; Kern, J.; Davis, L.; Miura, R. E.; Nakazato, T.; Sugimoto, K.; Kosugi, G.; Akiyama, E.; Muders, D.; Wyrowski, F.; Williams, S.; Lightfoot, J.; Kent, B.; Momjian, E.; Hunter, T.; ALMA Pipeline Team

    2015-12-01

    The ALMA Pipeline is the automated data reduction tool that runs on ALMA data. Current version of the ALMA pipeline produces science quality data products for standard interferometric observing modes up to calibration process. The ALMA Pipeline is comprised of (1) heuristics in the form of Python scripts that select the best processing parameters, and (2) contexts that are given for book-keeping purpose of data processes. The ALMA Pipeline produces a "weblog" that showcases detailed plots for users to judge how each step of calibration processes are treated. The ALMA Interferometric Pipeline was conditionally accepted in March 2014 by processing Cycle 0 and Cycle 1 data sets. From Cycle 2, ALMA Pipeline is used for ALMA data reduction and quality assurance for the projects whose observing modes are supported by the ALMA Pipeline. Pipeline tasks are available based on CASA version 4.2.2, and the first public pipeline release called CASA 4.2.2-pipe has been available since October 2014. One can reduce ALMA data both by CASA tasks as well as by pipeline tasks by using CASA version 4.2.2-pipe.

  10. Determination and identification of synthetic cannabinoids and their metabolites in different matrices by modern analytical techniques – a review

    Energy Technology Data Exchange (ETDEWEB)

    Znaleziona, Joanna; Ginterová, Pavlína; Petr, Jan [Regional Centre of Advanced Technologies and Materials, Department of Analytical Chemistry, Faculty of Science, Palacký University, 17. Listopadu 12, Olomouc CZ-77146 (Czech Republic); Ondra, Peter; Válka, Ivo [Department of Forensic Medicine and Medical Law Faculty Hospital, Hněvotínská 3, Olomouc CZ-77146 (Czech Republic); Ševčík, Juraj [Regional Centre of Advanced Technologies and Materials, Department of Analytical Chemistry, Faculty of Science, Palacký University, 17. Listopadu 12, Olomouc CZ-77146 (Czech Republic); Chrastina, Jan [Institute of Special Education Studies, Faculty of Education, Palacký University, Žižkovo náměsti 5, Olomouc CZ-77146 (Czech Republic); Maier, Vítězslav, E-mail: vitezslav.maier@upol.cz [Regional Centre of Advanced Technologies and Materials, Department of Analytical Chemistry, Faculty of Science, Palacký University, 17. Listopadu 12, Olomouc CZ-77146 (Czech Republic)

    2015-05-18

    Highlights: • Synthetic cannabinoids from analytical point of view. • Determination and identification methods of synthetic cannabinoids in different matrices. • Analytical techniques used from thin layer chromatography to high resolution mass spectrometry. • Detailed survey of gas and liquid chromatography methods for synthetic cannabinoids analysis. - Abstract: Synthetic cannabinoids have gained popularity due to their easy accessibility and psychoactive effects. Furthermore, they cannot be detected in urine by routine drug monitoring. The wide range of active ingredients in analyzed matrices hinders the development of a standard analytical method for their determination. Moreover, their possible side effects are not well known which increases the danger. This review is focused on the sample preparation and the determination of synthetic cannabinoids in different matrices (serum, urine, herbal blends, oral fluid, hair) published since 2004. The review includes separation and identification techniques, such as thin layer chromatography, gas and liquid chromatography and capillary electrophoresis, mostly coupled with mass spectrometry. The review also includes results by spectral methods like infrared spectroscopy, nuclear magnetic resonance or direct-injection mass spectrometry.

  11. Identification of loci affecting accumulation of secondary metabolites in tomato fruit of a Solanum lycopersicum × Solanum chmielewskii introgression line population

    NARCIS (Netherlands)

    Ballester Frutos, A.R.; Tikunov, Yury; Molthoff, Jos; Grandillo, Silvana; Viquez-Zamora, Marcela; Vos, de Ric; Maagd, de Ruud A.; Heusden, van Sjaak; Bovy, Arnaud G.

    2016-01-01

    Semi-polar metabolites such as flavonoids, phenolic acids, and alkaloids are very important health-related compounds in tomato. As a first step to identify genes responsible for the synthesis of semi-polar metabolites, quantitative trait loci (QTLs) that influence the semi-polar metabolite

  12. Bioactive endophytic fungi isolated from Caesalpinia echinata Lam. (Brazilwood and identification of beauvericin as a trypanocidal metabolite from Fusarium sp.

    Directory of Open Access Journals (Sweden)

    Fernanda Fraga Campos

    2015-02-01

    Full Text Available Aiming to identify new sources of bioactive secondary metabolites, we isolated 82 endophytic fungi from stems and barks of the native Brazilian tree Caesalpinia echinata Lam. (Fabaceae. We tested their ethyl acetate extracts in several in vitro assays. The organic extracts from three isolates showed antibacterial activity against Staphylococcus aureus and Escherichia coli [minimal inhibitory concentration (MIC 32-64 μg/mL]. One isolate inhibited the growth of Salmonella typhimurium (MIC 64 μg/mL and two isolates inhibited the growth of Klebsiella oxytoca (MIC 64 μg/mL, Candida albicans and Candida tropicalis (MIC 64-128 μg/mL. Fourteen extracts at a concentration of 20 μg/mL showed antitumour activities against human breast cancer and human renal cancer cells, while two isolates showed anti-tumour activities against human melanoma cancer cells. Six extracts were able to reduce the proliferation of human peripheral blood mononuclear cells, indicating some degree of selective toxicity. Four isolates were able to inhibit Leishmania (Leishmania amazonensis and one isolate inhibited Trypanosoma cruzi by at least 40% at 20 μg/mL. The trypanocidal extract obtained from Fusarium sp. [KF611679] culture was subjected to bioguided fractionation, which revealed beauvericin as the compound responsible for the observed toxicity of Fusarium sp. to T. cruzi. This depsipeptide showed a half maximal inhibitory concentration of 1.9 μg/mL (2.43 μM in a T. cruzi cellular culture assay.

  13. CLUSEAN: a computer-based framework for the automated analysis of bacterial secondary metabolite biosynthetic gene clusters.

    Science.gov (United States)

    Weber, T; Rausch, C; Lopez, P; Hoof, I; Gaykova, V; Huson, D H; Wohlleben, W

    2009-03-10

    Bacterial secondary metabolites are an important source of antimicrobial and cytostatic drugs. These molecules are often synthesized in a stepwise fashion by multimodular megaenzymes that are encoded in clusters of genes encoding enzymes for precursor supply and modification. In this work,we present an open source software pipeline, CLUSEAN (CLUster SEquence ANalyzer) that helps to annotate and analyze such gene clusters. CLUSEAN integrates standard analysis tools, like BLAST and HMMer, with specific tools for the identification of the functional domains and motifs in nonribosomal peptide synthetases (NRPS)/type I polyketide synthases (PKS) and the prediction of specificities of NRPS.

  14. Toscana virus meningitis case in Switzerland: an example of the ezVIR bioinformatics pipeline utility for the identification of emerging viruses.

    Science.gov (United States)

    Cordey, S; Bel, M; Petty, T J; Docquier, M; Sacco, L; Turin, L; Cherpillod, P; Emonet, S; Louis-Simonet, M; Zdobnov, E M; Ambrosioni, J; Kaiser, L

    2015-04-01

    Toscana virus (TOSV) represents a frequent cause of viral meningitis in the Mediterranean Basin that remains neglected in neighbouring countries. We report a documented TOSV meningitis case in a traveller returning from Tuscany to Switzerland. While routine serological and PCR assays could not discriminate between TOSV and Sandfly fever Naples virus infection, a high-throughput sequencing performed directly on the cerebrospinal fluid specimen and analysed with the ezVIR pipeline provided an unequivocal viral diagnostic. TOSV could be unequivocally considered as the aetiological agent, proving the potential of ezVIR to improve standard diagnostics in cases of infection with uncommon or emerging viruses.

  15. A streamlined approach for pipeline integrity management

    Energy Technology Data Exchange (ETDEWEB)

    Porter, T.R. [Tuboscope Pipeline Services, Houston, TX (United States); Marr, J.E. [Marr and Associates, A Tuboscope Company, Calgary, AB (Canada)

    2004-07-01

    While regulations call for safe and reliable operation of pipelines, business calls for economic return and reduced liability. This paper presented a system that provides rapid, comprehensive and economic improvements for pipeline integrity decision support. The first phase of a pipeline integrity management plan (IMP) involves the identification of integrity threats to the pipeline. This may involve 22 root causes as defined by the Pipeline Research Council International (PRCI), grouped into 9 categories of related failure types, further grouped into time related defect types. Time dependent defects include external corrosion, internal corrosion and stress corrosion cracking. Stable defects include manufacturing related or welding defects, while time independent defects include mechanical damage, incorrect operations and outside forces. In designing an IMP, high consequence areas (HCAs) must be defined along with the integrity threats that could affect the pipeline. A baseline risk assessment is then performed using data from the integrity threat models to identify risks areas, individual lines, pipe segments or joints. Integrity management decisions are made based on the outcome of initial assessments, resulting in integrity assessment tools such as in line inspection (ILI) technologies, direct assessment (DA), and hydrostatic testing. Pipeline engineers benefit from having ILI, DA and other data integrated and interacting with geographic information system (GIS) data. This paper presented the LinaView PRO{sup TM} IMP tool developed by Tuboscope that enhances dig smart excavation decision making; remediation and mitigation planning; responding to one-call emergency response; implementation of government regulations; HCA identification; integration of a wide variety of data; comprehensive dynamic segmentation; and, data validation in support of risk assessment. The objective of an IMP is the safe and reliable delivery system for oil and gas product to markets. 9

  16. Identification of liver protein targets modified by tienilic acid metabolites using a two-dimensional Western blot-mass spectrometry approach

    Science.gov (United States)

    Methogo, Ruth Menque; Dansette, Patrick M.; Klarskov, Klaus

    2007-12-01

    A combined approach based on two-dimensional electrophoresis-immuno-blotting and nanoliquid chromatography coupled on-line with electrospray ionization mass spectrometry (nLC-MS/MS) was used to identify proteins modified by a reactive intermediate of tienilic acid (TA). Liver homogenates from rats exposed to TA were fractionated using ultra centrifugation; four fractions were obtained and subjected to 2D electrophoresis. Following transfer to PVDF membranes, modified proteins were visualized after India ink staining, using an anti-serum raised against TA and ECL detection. Immuno-reactive spots were localized on the PVDF membrane by superposition of the ECL image, protein spots of interest were excised, digested on the membrane with trypsin followed by nLC-MS/MS analysis and protein identification. A total of 15 proteins were identified as likely targets modified by a TA reactive metabolite. These include selenium binding protein 2, senescence marker protein SMP-30, adenosine kinase, Acy1 protein, adenosylhomocysteinase, capping protein (actin filament), protein disulfide isomerase, fumarylacetoacetase, arginase chain A, ketohexokinase, proteasome endopeptidase complex, triosephosphate isomerase, superoxide dismutase, dna-type molecular chaperone hsc73 and malate dehydrogenase.

  17. Global metabolite profiling and diagnostic ion filtering strategy by LC-QTOF MS for rapid identification of raw and processed pieces of Rheum palmatum L.

    Science.gov (United States)

    Liu, Ying; Li, Li; Xiao, Yong-Qing; Yao, Jia-Qi; Li, Peng-Yuan; Yu, Ding-Rong; Ma, Yin-Lian

    2016-02-01

    Due to its variety of functions, rhubarb has been used for thousands of years in many countries. It is commonly used after processing. Processing usually affect the chemical profile and the contents of active compounds in herbals, leading to changes of their bioactivities. Here, an approach of metabolite profiling and diagnostic ion filtering strategy with liquid chromatography-quadrupole/time-of-flight mass spectrometry was established for rapid identification of raw and processed pieces of Rheum palmatum L. (RPL). The comprehensive and unbiased information of 30 batches of RPL covering raw and two general processing methods were given by metabolomic profiles. Using molecular feature extraction algorithm, non-targeted compounds were analyzed in minutes. In total, 73 characteristic markers were extracted and identified by diagnostic ion filtering. They have been further analyzed by partial least squares-support vector machine-based pattern recognition. The comprehensive and rapid method for raw and processed pieces of RPL classification shows good sensitivity, specificity and prediction performance.

  18. Comparative in vitro metabolism of the 'designer' steroid estra-4,9-diene-3,17-dione between the equine, canine and human: identification of target metabolites for use in sports doping control.

    Science.gov (United States)

    Scarth, James P; Clarke, Adam D; Teale, Philip; Pearce, Clive M

    2010-10-01

    Effective detection of the abuse of androgenic-anabolic steroids in human and animal sports often requires knowledge of the drug's metabolism in order to target appropriate urinary metabolites. 'Designer' steroids are problematic since it is difficult to obtain ethical approval for in vivo metabolism studies due to a lack of a toxicological profile. In this study, the in vitro metabolism of estra-4,9-diene-3,17-dione is reported for the first time. This is also the first study comparing the metabolism of a designer steroid in the three major species subject to sport's doping control; namely the equine, canine and human. In order to allow the retrospective analysis of sample testing data, the use of a high-resolution (HR) accurate-mass Thermo LTQ-Orbitrap LC-MS instrument was employed for metabolite identification of underivatised sample extracts. The full scan HR-LC-MS Orbitrap data was complimented by several further experiments targeted at elucidating more detailed structural information for the most abundant metabolites. These included; HR-LC-MS/MS of the underivatised metabolites, functional group selective chemical derivatisation followed by full scan HR-LC-MS, enzyme inhibition experiments and full scan electron ionization GC-MS analysis of methoxyamine-trimethylsilyl derivatives. The major metabolite detected in all species, and therefore the most suitable candidate for screening of estra-4,9-diene-3,17-dione abuse, was proposed to be an isomer of 17-hydroxy-estra-4,9-dien-3-one. Less significant metabolic pathways in all species included hydroxylation and reduction followed by hydroxylation. Reductive metabolism in the canine was less significant than in the other two species, while the equine was unique in producing a di-reduced metabolite (proposed to be an isomer of estra-4,9-diene-3,17-diol) and also relatively large quantities of d-ring hydroxy and hydroxy-reduced metabolites.

  19. Liquid Chromatography Electrospray Ionization Tandem Mass Spectrometric (LC/ESI-MS/MS Study for the Identification and Characterization of In Vivo Metabolites of Cisplatin in Rat Kidney Cancer Tissues: Online Hydrogen/Deuterium (H/D Exchange Study.

    Directory of Open Access Journals (Sweden)

    Raju Bandu

    Full Text Available In vivo rat kidney tissue metabolites of an anticancer drug, cisplatin (cis-diamminedichloroplatinum [II] (CP which is used for the treatment of testicular, ovarian, bladder, cervical, esophageal, small cell lung, head and neck cancers, have been identified and characterized by using liquid chromatography positive ion electrospray ionization tandem mass spectrometry (LC/ESI-MS/MS in combination with on line hydrogen/deuterium exchange (HDX experiments. To identify in vivo metabolites, kidney tissues were collected after intravenous administration of CP to adult male Sprague-Dawley rats (n = 3 per group. The tissue samples were homogenized and extracted using newly optimized metabolite extraction procedure which involves liquid extraction with phosphate buffer containing ethyl acetate and protein precipitation with mixed solvents of methanol-water-chloroform followed by solid-phase clean-up procedure on Oasis HLB 3cc cartridges and then subjected to LC/ESI-HRMS analysis. A total of thirty one unknown in vivo metabolites have been identified and the structures of metabolites were elucidated using LC-MS/MS experiments combined with accurate mass measurements. Online HDX experiments have been used to further support the structural characterization of metabolites. The results showed that CP undergoes a series of ligand exchange biotransformation reactions with water and other nucleophiles like thio groups of methionine, cysteine, acetylcysteine, glutathione and thioether. This is the first research approach focused on the structure elucidation of biotransformation products of CP in rats, and the identification of metabolites provides essential information for further pharmacological and clinical studies of CP, and may also be useful to develop various effective new anticancer agents.

  20. Identification of 6-hydroxy-trans,trans-2,4-hexadienoic acid, a novel ring-opened urinary metabolite of benzene

    Energy Technology Data Exchange (ETDEWEB)

    Kline, S.A.; Robertson, J.F.; Grotz, V.L.; Goldstein, B.D.; Witz, G. (Robert Wood Johnson Medical School, Piscataway, NJ (United States) Environmental and Occupational Health Sciences Institute, Piscataway, NJ (United States))

    1993-09-01

    The authors have studied the in vivo metabolism of benzene in mice to ring-opened compounds excreted in urine. Male CD-1 mice were treated intraperitoneally with benzene (110-440 mg/kg), [[sup 14]C] benzene (220 mg/kg) or trans,trans-muconaldehyde (MUC; 4 mg/kg), a microsomal, hematotoxic metabolite of benzene. Urine, collected over 24 hr, was extracted and analyzed by HPLC with a diode-array detector and by scintillation counting. In addition to trans,trans-muconic acid, previously the only known ring-opened urinary benzene metabolite, a new metabolite, 6-hydroxy-trans,trans-2,4-hexadienoic acid, was detected in urine of mice treated with either benzene or MUC. The authors identified the new metabolite based on coelution of metabolites and UV spectral comparison with authentic standards in unmethylated and methylated urine extracts. Results presented here are consistent with the intermediacy of the ring-opened metabolites.

  1. Holdup Measurement of Pipeline

    Institute of Scientific and Technical Information of China (English)

    LU; Wen-guang; XU; Zheng

    2015-01-01

    This research mainly adopts gamma spectroscopy to detect the pipeline retention.The calculation of retention of uranium has been obtained based on the intensity of gamma rays of 185.715 keV emitted by 235U,and the analysis method for the pipeline retention has been established.

  2. Slurry pipeline hydrostatic testing

    Energy Technology Data Exchange (ETDEWEB)

    Betinol, Roy G.; Navarro Rojas, Luis Alejandro [BRASS Chile S.A., Santiago (Chile)

    2009-07-01

    The transportation of concentrates and tailings through long distance pipeline has been proven in recent years to be the most economic, environmentally friendly and secure means of transporting of mine products. This success has led to an increase in the demand for long distance pipeline throughout the mining industry. In year 2007 alone, a total of over 500 km of pipeline has been installed in South America alone and over 800 km are in the planning stages. As more pipelines are being installed, the need to ensure its operating integrity is ever increasing. Hydrostatic testing of long distance pipeline is one of the most economical and expeditious way to proving the operational integrity of the pipe. The intent of this paper is to show the sound reasoning behind construction hydro testing and the economic benefit it presents. It will show how hydro test pressures are determined based on ASME B31.11 criteria. (author)

  3. Slurry pipeline design approach

    Energy Technology Data Exchange (ETDEWEB)

    Betinol, Roy; Navarro R, Luis [Brass Chile S.A., Santiago (Chile)

    2009-12-19

    Compared to other engineering technologies, the design of a commercial long distance Slurry Pipeline design is a relatively new engineering concept which gained more recognition in the mid 1960 's. Slurry pipeline was first introduced to reduce cost in transporting coal to power generating units. Since then this technology has caught-up worldwide to transport other minerals such as limestone, copper, zinc and iron. In South America, the use of pipeline is commonly practiced in the transport of Copper (Chile, Peru and Argentina), Iron (Chile and Brazil), Zinc (Peru) and Bauxite (Brazil). As more mining operations expand and new mine facilities are opened, the design of the long distance slurry pipeline will continuously present a commercially viable option. The intent of this paper is to present the design process and discuss any new techniques and approach used today to ensure a better, safer and economical slurry pipeline. (author)

  4. Astronomical pipeline processing using fuzzy logic

    Science.gov (United States)

    Shamir, Lior; Nemiroff, Robert J. Nemiroff

    2008-01-01

    Fundamental astronomical questions on the composition of the universe, the abundance of Earth-like planets, and the cause of the brightest explosions in the universe are being attacked by robotic telescopes costing billions of dollars and returning vast pipelines of data. The success of these programs depends on the accuracy of automated real time processing of images never seen by a human, and all predicated on fast and accurate automatic identifications of known astronomical objects and new astronomical transients. In this paper the needs of modern astronomical pipelines are discussed in the light of fuzzy-logic based decision-making. Several specific fuzzy-logic algorithms have been develop for the first time for astronomical purposes, and tested with excellent results on a test pipeline of data from the existing Night Sky Live sky survey.

  5. Motif-Independent De Novo Detection of Secondary Metabolite Gene Clusters – Towards Identification of Novel Secondary Metabolisms from Filamentous Fungi -

    Directory of Open Access Journals (Sweden)

    Myco eUmemura

    2015-05-01

    Full Text Available Secondary metabolites are produced mostly by clustered genes that are essential to their biosynthesis. The transcriptional expression of these genes is often cooperatively regulated by a transcription factor located inside or close to a cluster. Most of the secondary metabolism biosynthesis (SMB gene clusters identified to date contain so-called core genes with distinctive sequence features, such as polyketide synthase (PKS and non-ribosomal peptide synthetase (NRPS. Recent efforts in sequencing fungal genomes have revealed far more SMB gene clusters than expected based on the number of core genes in the genomes. Several bioinformatics tools have been developed to survey SMB gene clusters using the sequence motif information of the core genes, including SMURF and antiSMASH.More recently, accompanied by the development of sequencing techniques allowing to obtain large-scale genomic and transcriptomic data, motif-independent prediction methods of SMB gene clusters, including MIDDAS-M, have been developed. Most these methods detect the clusters in which the genes are cooperatively regulated at transcriptional levels, thus allowing the identification of novel SMB gene clusters regardless of the presence of the core genes. Another type of the method, MIPS-CG, uses the characteristics of SMB genes, which are highly enriched in non-syntenic blocks (NSBs, enabling the prediction even without transcriptome data although the results have not been evaluated in detail. Considering that large portion of SMB gene clusters might be sufficiently expressed only in limited uncommon conditions, it seems that prediction of SMB gene clusters by bioinformatics and successive experimental validation is an only way to efficiently uncover hidden SMB gene clusters. Here, we describe and discuss possible novel approaches for the determination of SMB gene clusters that have not been identified using conventional methods.

  6. Toxicological screening of human plasma by on-line SPE-HPLC-DAD: identification and quantification of basic drugs and metabolites.

    Science.gov (United States)

    Mut, Ludmila; Grobosch, Thomas; Binscheck-Domaß, Torsten; Frenzel, Wolfgang

    2015-06-01

    An automated multi-analyte screening method for the identification and quantification of 92 drugs and metabolites based on on-line solid-phase extraction-high-performance liquid chromatography-diode array detection technique was developed and successfully validated. In addition, a database with 870 entries including UV-spectra, relative/retention times and response factors of toxicologically relevant compounds was created. Plasma samples (0.2 mL) were treated with methanol, diluted with buffer and on-line extracted (Strata X, 20 ×2 mm, 25 µm) at pH 9. Analytical separation was carried out on a Gemini NX column (150 ×4.6 mm, 3 µm) using gradient elution with acetonitrile-water (90:10,v/v) and 0.05 m potassium dihydrogen phosphate buffer (pH 2.3). Linear calibration curves with correlation coefficients ≥0.9950 were obtained for 78 analytes. As an additional benefit, the newly developed method allows the quantification of 42 analytes (e.g. antidepressants, neuroleptics and anticonvulsants) in a concentration range suitable for therapeutic drug monitoring. Limits of quantitation ranged from 0.02 mg/L (chlordiazepoxide) to 3.4 mg/L (mexiletine). Inter- and intra-day precisions of quality control samples (low/high) were better than 15% (zolpidem) and accuracy (bias) ranged from -11% (opipramol, venlafaxine) to 11% (venlafaxine, trazodone). Tests for carry-over and sample stability under different storage conditions were also performed and stability was adequate. Four cases of poisoning analysis are presented.

  7. Characterizing protein modifications by reactive metabolites using magnetic bead bioreactors and LC-MS/MS.

    Science.gov (United States)

    Li, Dandan; Fu, You-Jun; Rusling, James F

    2015-03-18

    We report here label-free metabolite-protein adduct detection and identification employing magnetic beads coated with metabolic enzymes as bioreactors to generate metabolites and possible metabolite-protein adducts for analysis by liquid chromatography-tandem mass spectrometry.

  8. Separation, purification and identification of the major selenium metabolite from human urine by multi-dimensional HPLC-ICP-MS and APCI-MS

    DEFF Research Database (Denmark)

    Gammelgaard, Bente; Madsen, K.G.; Bjerrum, J.

    2003-01-01

    volunteers were collected and analysed by ion-pair chromatography with ICP-MS detection for this major selenium metabolite. Samples containing the metabolite were pooled and solid phase extracted to remove ionic substances. The extracted pool was purified and preconcentrated twice by preparative reversed...

  9. SSR_pipeline--computer software for the identification of microsatellite sequences from paired-end Illumina high-throughput DNA sequence data

    Science.gov (United States)

    Miller, Mark P.; Knaus, Brian J.; Mullins, Thomas D.; Haig, Susan M.

    2013-01-01

    SSR_pipeline is a flexible set of programs designed to efficiently identify simple sequence repeats (SSRs; for example, microsatellites) from paired-end high-throughput Illumina DNA sequencing data. The program suite contains three analysis modules along with a fourth control module that can be used to automate analyses of large volumes of data. The modules are used to (1) identify the subset of paired-end sequences that pass quality standards, (2) align paired-end reads into a single composite DNA sequence, and (3) identify sequences that possess microsatellites conforming to user specified parameters. Each of the three separate analysis modules also can be used independently to provide greater flexibility or to work with FASTQ or FASTA files generated from other sequencing platforms (Roche 454, Ion Torrent, etc). All modules are implemented in the Python programming language and can therefore be used from nearly any computer operating system (Linux, Macintosh, Windows). The program suite relies on a compiled Python extension module to perform paired-end alignments. Instructions for compiling the extension from source code are provided in the documentation. Users who do not have Python installed on their computers or who do not have the ability to compile software also may choose to download packaged executable files. These files include all Python scripts, a copy of the compiled extension module, and a minimal installation of Python in a single binary executable. See program documentation for more information.

  10. Use of liquid chromatography/electrospray ionization tandem mass spectrometry to study the degradation pathways of terbuthylazine (TER) by Typha latifolia in constructed wetlands: identification of a new TER metabolite.

    Science.gov (United States)

    Gikas, Evagelos; Papadopoulos, Nikolaos G; Bazoti, Fotini N; Zalidis, Georgios; Tsarbopoulos, Anthony

    2012-01-30

    S-Triazines are used worldwide as herbicides for agricultural and non-agricultural purposes. Although terbuthylazine (TER) is the second most frequently used S-triazine, there is limited information on its metabolism. For this reason, an analytical method based on liquid chromatography/electrospray ionization tandem mass spectrometry (LC-ESI MS/MS) has been developed aiming at the identification of TER and its five major metabolites (desisopropyl-hydroxy-atrazine, desethyl-hydroxy-terbuthylazine, desisopropyl-atrazine, hydroxy-terbuthylazine and desethyl-terbuthylazine) in constructed wetland water samples. The separation of TER and its major metabolites was performed by reversed-phase high-performance liquid chromatography (HPLC) on a C(8) column using a gradient elution of aqueous acetic acid 1% (solvent A) and acetonitrile (solvent B), followed by MS/MS analysis on a triple quadrupole mass spectrometer. The data-depended analysis (DDA) scan approach has been employed and the main degradation pathways of both hydroxyl and chloro (dealkylated and alkylated) metabolites are elucidated through the tandem mass spectral (MS/MS) interpretation of triazine fragments under CID conditions. In addition, another major metabolite of TER, namely N2-tert-butyl-N4-ethyl-6-methoxy-1,3,5-triazine-2,4-diamine, has been identified. This methodology can be further employed in biodegradation studies of TER, thus assisting the assessment of its environmental impact. Copyright © 2011 John Wiley & Sons, Ltd.

  11. Metabolism is an important route of pentamidine elimination in the rat. Disposition of {sup 14}C-pentamidine and identification of metabolites in urine us liquid chromatography-tandem mass spectrometry

    Energy Technology Data Exchange (ETDEWEB)

    Bronner, U.; Nordin, J.; Abdi, Y.A.; Gustafsson, L.L. [Huddinge Univ. Hospital, Karolinska Inst., Unit of Tropical Pharmacology, Div. of Clinical Pharmacology and Div. of Infectious Diseases, huddinge (Sweden); Ericsson, Oe.; Wikstroem, I. [Huddinge Univ. Hospital, Hospital Pharmacy, Huddinge (Sweden); Hall, J.E. [Univ. of North Carolina at Chapel Hill, Dept. of Epidemiology, North Carolina (United States); Tidwell, R.R. [Univ. of North Carolina at Chapel Hill, Dept. of Pathology, North Carolina (United States)

    1995-08-01

    This study assesses the contribution of metabolism for the disposition of pentamidine in the rat. With the use of {sup 14}C-labelled compound, the excretion of radioactivity in urine and faeces has been studied in four rats during 44 days after a single intravenous injection of the drug. The urinary and faecal excretion of the radioactivity were of equal importance; 22{+-}2% (mean{+-}S.D.) and 25{+-}4% being detected in urine and faeces, respectively. The activity organs and tissues at 44 days after drug administration was also measured and amounted to 21{+-}5% of the administered dose. Using HPLC the proportion of metabolites in urine in relation to unchanged pentamidine increased with time after dose, being 76{+-}15% (mean{+-}S.D.) of the total excreted radioactivity on day 1 and 97{+-}1% on day 6. HPLC - tandem mass spectrometry was used for identification of metabolites in urine obtained from four rats given unlabelled pentamidine. Using synthetic reference compounds and the selective MS/MS mode four oxidized metabolites of pentamidine were identified either by direct injection into the system or by analyses of extracted urine. Thus, a substantial part of pentamidine is excreted as metabolites in urine. (au) 14 refs.

  12. Forecasting and Evaluation of Gas Pipelines Geometric Forms Breach Hazard

    Science.gov (United States)

    Voronin, K. S.

    2016-10-01

    Main gas pipelines during operation are under the influence of the permanent pressure drops which leads to their lengthening and as a result, to instability of their position in space. In dynamic systems that have feedback, phenomena, preceding emergencies, should be observed. The article discusses the forced vibrations of the gas pipeline cylindrical surface under the influence of dynamic loads caused by pressure surges, and the process of its geometric shape deformation. Frequency of vibrations, arising in the pipeline at the stage preceding its bending, is being determined. Identification of this frequency can be the basis for the development of a method of monitoring the technical condition of the gas pipeline, and forecasting possible emergency situations allows planning and carrying out in due time reconstruction works on sections of gas pipeline with a possible deviation from the design position.

  13. Natural Gas Liquid Pipelines

    Data.gov (United States)

    Department of Homeland Security — Natural gas interstate and intrastate pipelines in the United States. Based on a variety of sources with varying scales and levels of accuracy and therefore accuracy...

  14. BSEE_Pacific_Pipelines

    Data.gov (United States)

    Bureau of Ocean Energy Management, Department of the Interior — This data set contains the locations of oil and gas pipelines in the Bureau of Safety and Environmental Enforcement Pacific OCS Region

  15. Central oxygen pipeline failure

    African Journals Online (AJOL)

    Anaesthetic and critical care staff play a governing role in the comprehension of a ... complete central oxygen pipeline failure occurred throughout. Tygerberg Hospital. ..... emergency stations and at plant room emergency supply manifolds.

  16. 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...

  17. Nearshore Pipeline Installation Methods.

    Science.gov (United States)

    1981-08-01

    179. 5. Aldridge, R. G., and Bomba , J. G., "Deep Water Pipelines - Interdependence of Design and Construction", ASCE Paper. 6. American Society Civil...October 13, 1967. 24. Bomba , J. G. and Seeds, K. J., "Pipelining in 600 feet of water .... A Case Study of Washington Natural Gas Company’s Puget Sound...Crossing", Offshore Technology Conference, paper OTC 1188, 1970. 25. Bomba , J., "Submarine Pipe Construction Methods", Petroleum Engineer, Vol. 32

  18. Pipeline coating comparison methods for northern pipelines

    Energy Technology Data Exchange (ETDEWEB)

    Singh, P. [Shaw Pipe Protection, Calgary, AB (Canada); Purves, G.A. [Cimarron Engineering Ltd., Calgary, AB (Canada)

    2004-07-01

    Two high-quality pipe coatings designed for northern environments were compared for their relative costs and suitability for the conditions that will be encountered in the field. Coating selection should consider local conditions to achieve the optimum life-cycle costs for the system. Some of the key factors affecting the integrity of the protective coating on a pipe include the effects of cold temperature and soil types. In this study, both Fusion Bonded Epoxy (FBE) and High Performance Composite Coatings (HPCC) were evaluated for an entire pipeline installation in a northern environment, from the coating plant to the pipe trench. The evaluation focused on the advantages of better abrasion resistance of the HPCC coating. This was compared against the incremental cost of HPCC coating over FBE on large diameter NPS 30 to NPS 48 pipelines. The following parameters influenced the choice of coating: storage, transportation and handling; bending ability under cold weather conditions; pipe installation and backfilling; weld joint coatings; coating repair and cathodic protection and pipeline integrity. Some of the construction costs that are indirectly affected by the choice of pipe coating include right-of-way preparation and restoration; trenching; supervision, service and downtime and specialist crossings. It was concluded that HPCC has better resistance to abrasion than FBE and is more flexible in extremely cold temperatures. Standard FBE is about 10 per cent less expensive than HPCC. In general HPCC will require less coating protection than FBE, depending on site conditions. 3 refs., 18 tabs., 8 figs.

  19. Software for pipeline integrity administration

    Energy Technology Data Exchange (ETDEWEB)

    Soula, Gerardo; Perona, Lucas Fernandez [Gie SA., Buenos Aires (Argentina); Martinich, Carlos [Refinaria do Norte S. A. (REFINOR), Tartagal, Provincia de Salta (Argentina)

    2009-07-01

    A Software for 'pipeline integrity management' was developed. It allows to deal with Geographical Information and a PODS database (Pipeline Open database Standard) simultaneously, in a simple and reliable way. The premises for the design were the following: didactic, geo referenced, multiple reference systems. Program skills: 1.PODS+GIS: the PODS database in which the software is based on is completely integrated with the GIS module. 2 Management of different kinds of information: it allows to manage information on facilities, repairs, interventions, physical inspections, geographical characteristics, compliance with regulations, training, offline events, operation measures, O and M information treatment and importing specific data and studies in a massive way. It also assures the integrity of the loaded information. 3 Right of way survey: it allows to verify the class location, ROW occupation, sensitive areas identification and to manage landowners. 4 Risk analysis: it is done in a qualitative way, depending on the entered data, allowing the user to identify the riskiest stretches of the system. Either results from risk analysis, data and consultations made about the database, can be exported to standard formats. (author)

  20. Metabolic characterization of AH-7921, a synthetic opioid designer drug: in vitro metabolic stability assessment and metabolite identification, evaluation of in silico prediction, and in vivo confirmation.

    Science.gov (United States)

    Wohlfarth, Ariane; Scheidweiler, Karl B; Pang, Shaokun; Zhu, Mingshe; Castaneto, Marisol; Kronstrand, Robert; Huestis, Marilyn A

    2016-08-01

    AH-7921 (3,4-dichloro-N-[(1-dimethylamino)cyclohexylmethyl]benzamide) is a new synthetic opioid and has led to multiple non-fatal and fatal intoxications. To comprehensively study AH-7921 metabolism, we assessed human liver microsome (HLM) metabolic stability, determined AH-7921's metabolic profile after human hepatocytes incubation, confirmed our findings in a urine case specimen, and compared results to in silico predictions. For metabolic stability, 1 µmol/L AH-7921 was incubated with HLM for up to 1 h; for metabolite profiling, 10 µmol/L was incubated with pooled human hepatocytes for up to 3 h. Hepatocyte samples were analyzed by liquid chromatography quadrupole/time-of-flight high-resolution mass spectrometry (MS). High-resolution full scan MS and information-dependent acquisition MS/MS data were analyzed with MetabolitePilot™ (SCIEX) using multiple data processing algorithms. The presence of AH-7921 and metabolites was confirmed in the urine case specimen. In silico prediction of metabolite structures was performed with MetaSite™ (Molecular Discovery). AH-7921 in vitro half-life was 13.5 ± 0.4 min. We identified 12 AH-7921 metabolites after hepatocyte incubation, predominantly generated by demethylation, less dominantly by hydroxylation, and combinations of different biotransformations. Eleven of 12 metabolites identified in hepatocytes were found in the urine case specimen. One metabolite, proposed to be di-demethylated, N-hydroxylated and glucuronidated, eluted after AH-7921 and was the most abundant metabolite in non-hydrolyzed urine. MetaSite™ correctly predicted the two most abundant metabolites and the majority of observed biotransformations. The two most dominant metabolites after hepatocyte incubation (also identified in the urine case specimen) were desmethyl and di-desmethyl AH-7921. Together with the glucuronidated metabolites, these are likely suitable analytical targets for documenting AH-7921 intake. Copyright © 2015

  1. Comparison of triple quadrupole, hybrid linear ion trap triple quadrupole, time-of-flight and LTQ-Orbitrap mass spectrometers in drug discovery phase metabolite screening and identification in vitro--amitriptyline and verapamil as model compounds.

    Science.gov (United States)

    Rousu, Timo; Herttuainen, Jukka; Tolonen, Ari

    2010-04-15

    Liquid chromatography in combination with mass spectrometry (LC/MS) is a superior analytical technique for metabolite profiling and identification studies performed in drug discovery and development laboratories. In the early phase of drug discovery the analytical approach should be both time- and cost-effective, thus providing as much data as possible with only one visit to the laboratory, without the need for further experiments. Recent developments in mass spectrometers have created a situation where many different mass spectrometers are available for the task, each with their specific strengths and drawbacks. We compared the metabolite screening properties of four main types of mass spectrometers used in analytical laboratories, considering both the ability to detect the metabolites and provide structural information, as well as the issues related to time consumption in laboratory and thereafter in data processing. Human liver microsomal incubations with amitriptyline and verapamil were used as test samples, and early-phase 'one lab visit only' approaches were used with all instruments. In total, 28 amitriptyline and 69 verapamil metabolites were found and tentatively identified. Time-of-flight mass spectrometry (TOFMS) was the only approach detecting all of them, shown to be the most suitable instrument for elucidating as comprehensive metabolite profile as possible leading also to lowest overall time consumption together with the LTQ-Orbitrap approach. The latter however suffered from lower detection sensitivity and false negatives, and due to slow data acquisition rate required slower chromatography. Approaches with triple quadrupole mass spectrometry (QqQ) and hybrid linear ion trap triple quadrupole mass spectrometry (Q-Trap) provided the highest amount of fragment ion data for structural elucidation, but, in addition to being unable to produce very high-important accurate mass data, they suffered from many false negatives, and especially with the Qq

  2. Identification of an ISR-related metabolite produced by Pseudomonas chlororaphis O6 against the wildfire pathogen pseudomonas syringae pv.tabaci in tobacco.

    Science.gov (United States)

    Park, Myung Ryeol; Kim, Young Cheol; Park, Ju Yeon; Han, Song Hee; Kim, Kil Yong; Lee, Sun Woo; Kim, In Seon

    2008-10-01

    Pseudomonas chlororaphis O6 exhibits induced systemic resistance (ISR) against P. syringae pv. tabaci in tobacco. To identify one of the ISR metabolites, O6 cultures were extracted with organic solvents, and the organic extracts were subjected to column chromatography followed by spectroscopy analyses. The ISR bioassay-guided fractionation was carried out for isolation of the metabolite. Highresolution mass spectrometric analysis of the metabolite found C(9)H(9)O(3)N with an exact mass of 179.0582. LC/MS analysis in positive mode showed an (M+H)(+) peak at m/zeta 180. Nuclear magnetic resonance ((1)H, (13)C) analyses identified all protons and carbons of the metabolite. Based on the spectroscopy data, the metabolite was identified 4-(aminocarbonyl) phenylacetate (4-ACPA). 4-ACPA applied at 68.0 mM exhibited ISR activity at a level similar 1.0 mM salicylic acid. This is the first report to identify an ISR metabolite produced by P. chlororaphis O6 against the wildfire pathogen P. syringae pv. tabaci in tobacco.

  3. Identification and characterization of in vivo metabolites of asulacrine using advanced mass spectrophotometry technique in combination with improved data mining strategy.

    Science.gov (United States)

    Afzal, Attia; Zhong, Yunxi; Sarfraz, Muhammad; Peng, Ying; Sheng, Longsheng; Wu, Zimei; Sun, Jianguo; Wang, Guangji

    2016-04-29

    Asulacrine (ASL) is a broad-spectrum, antitumor drug whose data are promising for the treatment of breast and lung cancers; however, a high incidence of phlebitis hampered its further development. Phlebitis is associated with generation of reactive species. Asulacrine donates electrons and produces oxidative stress in chemical reactions. It was expected that ASL would actively metabolize to oxidized products through reactive intermediates and produce more products in vivo than reported and thus cause phlebitis. A comprehensive study was planned to investigate in vivo metabolism of ASL, using high-resolution mass spectrometry LC/IT-TOF MS in positive mode. Metabolites were detected by different software by applying annotated detection strategy. The possible metabolites and their product ions were simultaneously detected by segmented data acquisition to get accurate mass values. Segmented data acquisition improved signal-to-noise (S/N) ratio, which was helpful to detect metabolites and their fragments even when present in trace amounts. A total of 21 metabolites were detected in gender-based biological fluids and characterized by comparing their accurate mass values, fragmentation patterns, and relative retention times with that of ASL. Among previously reported glucuronosylation metabolites, some oxidation, hydroxylation, carboxylation, demethylation, hydrogenation, glutamination, and acetylcysteine conjugation were detected for the first time. Twenty metabolites were tentatively identified by using the annotated strategy for data acquisition and post-data mining.

  4. 77 FR 2126 - Pipeline Safety: Implementation of the National Registry of Pipeline and Liquefied Natural Gas...

    Science.gov (United States)

    2012-01-13

    ... Registry of Pipeline and Liquefied Natural Gas Operators AGENCY: Pipeline and Hazardous Materials Safety... registry of pipeline and liquefied natural gas operators. FOR FURTHER INFORMATION CONTACT: Jamerson Pender... 72878), titled: ``Pipeline Safety: Updates to Pipeline and Liquefied Natural Gas Reporting...

  5. Pipeliners go regulator shopping

    Energy Technology Data Exchange (ETDEWEB)

    Byfield, M.

    1996-12-09

    The weakening of Alberta`s regulatory grip on gas pipelines was discussed. Palliser Pipeline Limited has challenged Nova Corp`s monopoly by applying to the National Energy Board (NEB) for permission to build a 150-mile pipeline from Calgary to the Saskatchewan border. If the $350 million project proceeds, it would mean that gas would be flowing out of Alberta for the first time through a line that is not operated by Nova Corp. Palliser would operate with a lower shipping toll, set by the NEB rather than Alberta`s Energy and Utilities Board. Alliance Pipeline Ltd. will also apply to the NEB to build a 1850-mile pipeline that would originate in British Columbia, cross Alberta and terminate in Chicago. Nova Corp has implied that it might have to consider charging distance-based tolls if the Palliser bypass line proceeds. However, Palliser countered that it should not be necessary to change the postage stamp system for that small a fraction. Palliser suggested that Nova was simply reacting because it was facing competition for the first time. Final decision is in the hands of the federal government.

  6. Protecting a pipeline

    Energy Technology Data Exchange (ETDEWEB)

    Gray, D.H (Univ. of Michigan, Ann Arbor, MI (United States)); Garcia-Lopez, M. (Ingenieria y Geotecnia Ltda., Santafe de Bogota (Colombia))

    1994-12-01

    This article describes some of the difficulties in constructing an oil pipeline in Colombia across a forested mountain range that has erosion-prone slopes. Engineers are finding ways to protect the pipeline against slope failures and severe erosion problems while contending with threats of guerrilla attacks. Torrential rainfall, precipitous slopes, unstable soils, unfavorable geology and difficult access make construction of an oil pipeline in Colombia a formidable undertaking. Add the threat of guerrilla attacks, and the project takes on a new dimension. In the country's central uplands, a 76 cm pipeline traverses some of the most daunting and formidable terrain in the world. The right-of-way crosses rugged mountains with vertical elevations ranging from 300 m to 2,000 mm above sea level over a distance of some 30 km. The pipeline snakes up and down steep forested inclines in some spots and crosses streams and faults in others, carrying the country's major export--petroleum--from the Cusiana oil field, located in Colombia's lowland interior, to the coast.

  7. Pipelines. Economy's veins; Pipelines. Adern der Wirtschaft

    Energy Technology Data Exchange (ETDEWEB)

    Feizlmayr, Adolf; Goestl, Stefan [ILF Beratende Ingenieure, Muenchen (Germany)

    2011-02-15

    According to the existing prognoses more than 1 million km of gas pipelines, oil pipelines and water pipelines are built up to the year 2030. The predominant portion is from gas pipelines. The safe continued utilization of the aging pipelines is a large challenge. In addition, the diagnostic technology, the evaluation and risk assessment have to be developed further. With the design of new oil pipelines and gas pipelines, aspects of environmental protection, the energy efficiency of transport and thus the emission reduction of carbon dioxide, the public acceptance and the market strategy of the exporters gain in importance. With the offshore pipelines one soon will exceed the present border of 2,000 m depth of water and penetrate into larger sea depths.

  8. 77 FR 31827 - Pipeline Safety: Pipeline Damage Prevention Programs

    Science.gov (United States)

    2012-05-30

    ... Safety: Pipeline Damage Prevention Programs AGENCY: Pipeline and Hazardous Materials Safety... excavation damage prevention law enforcement programs; establish an administrative process for making... excavation damage prevention law enforcement programs; and establish the adjudication process...

  9. Metabolic profile of mephedrone: Identification of nor-mephedrone conjugates with dicarboxylic acids as a new type of xenobiotic phase II metabolites.

    Science.gov (United States)

    Linhart, Igor; Himl, Michal; Židková, Monika; Balíková, Marie; Lhotková, Eva; Páleníček, Tomáš

    2016-01-01

    Metabolic profile of mephedrone (4-methylmethcathinone, 4-MMC), a frequently abused recreational drug, was determined in rats in vivo. The urine of rats dosed with a subcutaneous bolus dose of 20mg 4-MMC/kg was analysed by LC/MS. Ten phase I and five phase II metabolites were identified by comparison of their retention times and MS(2) spectra with those of authentic reference standards and/or with the MS(2) spectra of previously identified metabolites. The main metabolic pathway was N-demethylation leading to normephedrone (4-methylcathinone, 4-MC) which was further conjugated with succinic, glutaric and adipic acid. Other phase I metabolic pathways included oxidation of the 4-methyl group, carbonyl reduction leading to dihydro-metabolites and ω-oxidation at the position 3'. Five of the metabolites detected, namely, 4-carboxynormephedrone (4-carboxycathinone, 4-CC), 4-carboxydihydronormephedrone (4-carboxynorephedrine, 4-CNE), hydroxytolyldihydro-normephedrone (4-hydroxymethylnorephedrine, 4-OH-MNE) and conjugates of 4-MC with glutaric and adipic acid, have not been reported as yet. The last two conjugates represent a novel, hitherto unexploited, type of phase II metabolites in mammals together with an analogous succinic acid conjugate of 4-MC identified by Pozo et al. (2015). These conjugates might be potentially of great importance in the metabolism of other psychoactive amines.

  10. CPL: Common Pipeline Library

    Science.gov (United States)

    ESO CPL Development Team

    2014-02-01

    The Common Pipeline Library (CPL) is a set of ISO-C libraries that provide a comprehensive, efficient and robust software toolkit to create automated astronomical data reduction pipelines. Though initially developed as a standardized way to build VLT instrument pipelines, the CPL may be more generally applied to any similar application. The code also provides a variety of general purpose image- and signal-processing functions, making it an excellent framework for the creation of more generic data handling packages. The CPL handles low-level data types (images, tables, matrices, strings, property lists, etc.) and medium-level data access methods (a simple data abstraction layer for FITS files). It also provides table organization and manipulation, keyword/value handling and management, and support for dynamic loading of recipe modules using programs such as EsoRex (ascl:1504.003).

  11. Pipeline rehabilitation planning

    Energy Technology Data Exchange (ETDEWEB)

    Palmer-Jones, Roland; Hopkins, Phil; Eyre, David [PENSPEN (United Kingdom)

    2005-07-01

    An operator faced with an onshore pipeline that has extensive damage must consider the need for rehabilitation, the sort of rehabilitation to be used, and the rehabilitation schedule. This paper will consider pipeline rehabilitation based on the authors' experiences from recent projects, and recommend a simple strategy for planning pipeline rehabilitation. It will also consider rehabilitation options: external re-coating; internal lining; internal painting; programmed repairs. The main focus will be external re-coating. Consideration will be given to rehabilitation coating types, including tape wraps, epoxy, and polyurethane. Finally it will discuss different options for scheduling the rehabilitation of corrosion damage including: the statistical comparison of signals from inspection pigs; statistical comparison of selected measurements from inspection pigs and other inspections; the use of corrosion rates estimated for the mechanisms and conditions; expert judgement. (author)

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

    Science.gov (United States)

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

    2016-01-01

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

  13. Identification of metabolites and thermal transformation products of quinolones in raw cow's milk by liquid chromatography coupled to high-resolution mass spectrometry.

    Science.gov (United States)

    Junza, Alexandra; Barbosa, Sergio; Codony, M Rosa; Jubert, Anna; Barbosa, José; Barrón, Dolores

    2014-02-26

    The presence of residues of antibiotics, metabolites, and thermal transformation products (TPs), produced during thermal treatment to eliminate pathogenic microorganisms in milk, could represent a risk for people. Cow's milk samples spiked with enrofloxacin (ENR), ciprofloxacin (CIP), difloxacin (DIF), and sarafloxacin (SAR) and milk samples from cows medicated with ENR were submitted to several thermal treatments. The milk samples were analyzed by liquid chromatography-mass spectrometry (LC-MS) to find and identify TPs and metabolites. In this work, 27 TPs of 4 quinolones and 24 metabolites of ENR were found. Some of these compounds had been reported previously, but others were characterized for the first time, including lactose-conjugated CIP, the formamidation reaction for CIP and SAR, and hydroxylation or ketone formation to produce three different isomers for all quinolones studied.

  14. 78 FR 70623 - Pipeline Safety: Meeting of the Gas Pipeline Advisory Committee and the Liquid Pipeline Advisory...

    Science.gov (United States)

    2013-11-26

    ... gas pipelines and for hazardous liquid pipelines. Both committees were established under the Federal... Administration [Docket No. PHMSA-2009-0203] Pipeline Safety: Meeting of the Gas Pipeline Advisory Committee and the Liquid Pipeline Advisory Committee AGENCY: Pipeline and Hazardous Materials Safety...

  15. Crossing Active Faults on the Sakhalin II Onshore Pipeline Route: Pipeline Design and Risk Analysis

    Science.gov (United States)

    Mattiozzi, Pierpaolo; Strom, Alexander

    2008-07-01

    Twin oil (20 & 24 inch) and gas (20 & 48 inch) pipeline systems stretching 800 km are being constructed to connect offshore hydrocarbon deposits from the Sakhalin II concession in the North to an LNG plant and oil export terminal in the South of Sakhalin island. The onshore pipeline route follows a regional fault zone and crosses individual active faults at 19 locations. Sakhalin Energy, Design and Construction companies took significant care to ensure the integrity of the pipelines, should large seismic induced ground movements occur during the Operational life of the facilities. Complex investigations including the identification of the active faults, their precise location, their particular displacement values and assessment of the fault kinematics were carried out to provide input data for unique design solutions. Lateral and reverse offset displacements of 5.5 and 4.5 m respectively were determined as the single-event values for the design level earthquake (DLE)—the 1000-year return period event. Within the constraints of a pipeline route largely fixed, the underground pipeline fault crossing design was developed to define the optimum routing which would minimize stresses and strain using linepipe materials which had been ordered prior to the completion of detailed design, and to specify requirements for pipe trenching shape, materials, drainage system, etc. Detailed Design was performed with due regard to actual topography and to avoid the possibility of the trenches freezing in winter, the implementation of specific drainage solutions and thermal protection measures.

  16. Identification and comparison of marbofloxacin metabolites from the plasma of ball pythons (Python regius) and blue and gold macaws (Ara ararauna).

    Science.gov (United States)

    Hunter, R P; Koch, D E; Coke, R L; Carpenter, J W; Isaza, R

    2007-06-01

    Marbofloxacin is a veterinary only, synthetic, broad spectrum fluoroquinolone antimicrobial agent. In mammals, approximately 40% of the oral dose of marbofloxacin is excreted unchanged in the urine; the remaining is excreted via the bile as unchanged drug in the feces. The Vd ranges from 1.1 (cattle) to 1.3 (dog, goat, swine) L/kg. Because of extra-label use of marbofloxacin in birds and reptiles, this study was designed to determine the profile of metabolites in plasma and compare the circulating metabolite profile between a reptile and an avian species. Six adult ball pythons (Python regius) and 10 blue and gold macaws (Ara ararauna) were used in this study. The macaws were dosed both i.v. and p.o. with a single 2.5 mg/kg administration where as the pythons received a single 10 mg/kg dose both i.v. and p.o. The metabolite profiles of marbofloxacin in the plasma of these species were determined using a high performance liquid chromatography system with a mass spectrometer for detection (LC/MS/MS). Mass spectra data generated from the snake and bird plasma samples were compared with previously reported LC/MS/MS mass spectral data. Evidence does not suggest differences due to route of administration (i.v. vs. p.o.) in either species. Four chromatographic peaks with resulting daughter spectrum were identified and represent 12 possible metabolite structures. All of the proposed metabolites, except for the N-oxide, appear to be unique to macaws. The potential metabolites identified in macaws appear to be very different than those reported for chickens.

  17. The TROBAR pipeline

    Science.gov (United States)

    Stefanon, Mauro

    TROBAR is a 60cm robotic telescope installed at the Observatrio de Aras de los Olmos (OAO), approximately 100km north-west of Valencia (Spain). It is currently equipped with a 4K×4K optical camera covering a FoV of 30×30 arcmin^2. We are now implementing a pipeline for the automatic reduction of its data. In this paper we will present the main features of the pipeline, with particular care to some of the algorithms implemented to assess the quality of the produced data and showing their application to synthetic images.

  18. 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 b

  19. 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

  20. Characterization of a non-approved selective androgen receptor modulator drug candidate sold via the Internet and identification of in vitro generated phase-I metabolites for human sports drug testing.

    Science.gov (United States)

    Thevis, Mario; Lagojda, Andreas; Kuehne, Dirk; Thomas, Andreas; Dib, Josef; Hansson, Annelie; Hedeland, Mikael; Bondesson, Ulf; Wigger, Tina; Karst, Uwe; Schänzer, Wilhelm

    2015-06-15

    Potentially performance-enhancing agents, particularly anabolic agents, are advertised and distributed by Internet-based suppliers to a substantial extent. Among these anabolic agents, a substance referred to as LGD-4033 has been made available, comprising the core structure of a class of selective androgen receptor modulators (SARMs). In order to provide comprehensive analytical data for doping controls, the substance was obtained and characterized by nuclear magnetic resonance spectroscopy (NMR) and liquid chromatography/electrospray ionization high resolution/high accuracy tandem mass spectrometry (LC/ESI-HRMS). Following the identification of 4-(2-(2,2,2-trifluoro-1-hydroxyethyl)pyrrolidin-1-yl)-2-(trifluoromethyl)benzonitrile, the substance was subjected to in vitro metabolism studies employing human liver microsomes and Cunninghamella elegans (C. elegans) preparations as well as electrochemical metabolism simulations. By means of LC/ESI-HRMS, five main phase-I metabolites were identified as products of liver microsomal preparations including three monohydroxylated and two bishydroxylated species. The two most abundant metabolites (one mono- and one bishydroxylated product) were structurally confirmed by LC/ESI-HRMS and NMR. Comparing the metabolic conversion of 4-(2-(2,2,2-trifluoro-1-hydroxyethyl)pyrrolidin-1-yl)-2-(trifluoromethyl)benzonitrile observed in human liver microsomes with C. elegans and electrochemically derived metabolites, one monohydroxylated product was found to be predominantly formed in all three methodologies. The implementation of the intact SARM-like compound and its presumed urinary phase-I metabolites into routine doping controls is suggested to expand and complement existing sports drug testing methods. Copyright © 2015 John Wiley & Sons, Ltd.

  1. Volatile Metabolites

    Directory of Open Access Journals (Sweden)

    Daryl D. Rowan

    2011-11-01

    Full Text Available Volatile organic compounds (volatiles comprise a chemically diverse class of low molecular weight organic compounds having an appreciable vapor pressure under ambient conditions. Volatiles produced by plants attract pollinators and seed dispersers, and provide defense against pests and pathogens. For insects, volatiles may act as pheromones directing social behavior or as cues for finding hosts or prey. For humans, volatiles are important as flavorants and as possible disease biomarkers. The marine environment is also a major source of halogenated and sulfur-containing volatiles which participate in the global cycling of these elements. While volatile analysis commonly measures a rather restricted set of analytes, the diverse and extreme physical properties of volatiles provide unique analytical challenges. Volatiles constitute only a small proportion of the total number of metabolites produced by living organisms, however, because of their roles as signaling molecules (semiochemicals both within and between organisms, accurately measuring and determining the roles of these compounds is crucial to an integrated understanding of living systems. This review summarizes recent developments in volatile research from a metabolomics perspective with a focus on the role of recent technical innovation in developing new areas of volatile research and expanding the range of ecological interactions which may be mediated by volatile organic metabolites.

  2. Coherent pipeline for biomarker discovery using mass spectrometry and bioinformatics

    Directory of Open Access Journals (Sweden)

    Al-Shahib Ali

    2010-08-01

    Full Text Available Abstract Background Robust biomarkers are needed to improve microbial identification and diagnostics. Proteomics methods based on mass spectrometry can be used for the discovery of novel biomarkers through their high sensitivity and specificity. However, there has been a lack of a coherent pipeline connecting biomarker discovery with established approaches for evaluation and validation. We propose such a pipeline that uses in silico methods for refined biomarker discovery and confirmation. Results The pipeline has four main stages: Sample preparation, mass spectrometry analysis, database searching and biomarker validation. Using the pathogen Clostridium botulinum as a model, we show that the robustness of candidate biomarkers increases with each stage of the pipeline. This is enhanced by the concordance shown between various database search algorithms for peptide identification. Further validation was done by focusing on the peptides that are unique to C. botulinum strains and absent in phylogenetically related Clostridium species. From a list of 143 peptides, 8 candidate biomarkers were reliably identified as conserved across C. botulinum strains. To avoid discarding other unique peptides, a confidence scale has been implemented in the pipeline giving priority to unique peptides that are identified by a union of algorithms. Conclusions This study demonstrates that implementing a coherent pipeline which includes intensive bioinformatics validation steps is vital for discovery of robust biomarkers. It also emphasises the importance of proteomics based methods in biomarker discovery.

  3. Metabolism of Genipin in Rat and Identification of Metabolites by Using Ultraperformance Liquid Chromatography/Quadrupole Time-of-Flight Tandem Mass Spectrometry

    Directory of Open Access Journals (Sweden)

    Yue Ding

    2013-01-01

    Full Text Available The in vivo and in vitro metabolism of genipin was systematically investigated in the present study. Urine, plasma, feces, and bile were collected from rats after oral administration of genipin at a dose of 50 mg/kg body weight. A rapid and sensitive method using ultraperformance liquid chromatography coupled with electrospray ionization quadrupole time-of-flight tandem mass spectrometry (UPLC-Q/TOF MS was developed for analysis of metabolic profile of genipin in rat biological samples (urine, plasma, feces, and bile. A total of ten metabolites were detected and identified by comparing their fragmentation patterns with that of genipin using MetaboLynx software tools. On the basis of the chromatographic peak area, the sulfated and glucuronidated conjugates of genipin were identified as major metabolites. And the existence of major metabolites G1 and G2 was confirmed by the in vitro enzymatic study further. Then, metabolite G1 was isolated from rat bile by semipreparative HPLC. Its structure was unambiguously identified as genipin-1-o-glucuronic acid by comparison of its UV, IR, ESI-MS, 1H-NMR, and 13C-NMR spectra with conference. In general, genipin was a very active compound that would transform immediately, and the parent form of genipin could not be observed in rats biological samples. The biotransformation pathways of genipin involved demethylated, ring-opened, cysteine-conjugated, hydroformylated, glucuronidated, and sulfated transformations.

  4. Identification of glyceollin metabolites derived from conjugation with glutathione and glucuronic acid in rats by on-line liquid chromatography-electrospray ionization tandem mass spectrometry

    Science.gov (United States)

    Glyceollin-related metabolites produced in rats following oral glyceollin administration were screened and identified by precursor and product ion scanning using liquid chromatography, coupled on-line with electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS), to identify all glyceollin me...

  5. Condition Monitoring Of Operating Pipelines With Operational Modal Analysis Application

    Directory of Open Access Journals (Sweden)

    Mironov Aleksey

    2015-12-01

    Full Text Available In the petroleum, natural gas and petrochemical industries, great attention is being paid to safety, reliability and maintainability of equipment. There are a number of technologies to monitor, control, and maintain gas, oil, water, and sewer pipelines. The paper focuses on operational modal analysis (OMA application for condition monitoring of operating pipelines. Special focus is on the topicality of OMA for definition of the dynamic features of the pipeline (frequencies and mode shapes in operation. The research was conducted using two operating laboratory models imitated a part of the operating pipeline. The results of finite-element modeling, identification of pipe natural modes and its modification under the influence of virtual failure are discussed. The work considers the results of experimental research of dynamic behavior of the operating pipe models using one of OMA techniques and comparing dynamic properties with the modeled data. The study results demonstrate sensitivity of modal shape parameters to modification of operating pipeline technical state. Two strategies of pipeline repair – with continuously condition-based monitoring with proposed technology and without such monitoring, was discussed. Markov chain reliability models for each strategy were analyzed and reliability improvement factor for proposed technology of monitoring in compare with traditional one was evaluated. It is resumed about ability of operating pipeline condition monitoring by measuring dynamic deformations of the operating pipe and OMA techniques application for dynamic properties extraction.

  6. Sinopec: Pipeline Goes Ahead

    Institute of Scientific and Technical Information of China (English)

    Xie Ye

    2002-01-01

    @@ Asia's largest refinery, Sinopec Corp, will proceed with a 1,600-kilometre oil pipeline across southern provinces of China, although speculation continues to linger that the company will scrap the plan due to a postponement of the multi-million-dollar project.

  7. The NOAO Pipeline Data Manager

    Science.gov (United States)

    Hiriart, R.; Valdes, F.; Pierfederici, F.; Smith, C.; Miller, M.

    2004-07-01

    The Data Manager for NOAO Pipeline system is a set of interrelated components that are being developed to fulfill the pipeline system data needs. It includes: (1) management of calibration files (flat, bias, bad pixel mask and xtalk calibration data.); (2) management of the pipeline stages' configuration parameters; and (3) management of the pipeline processing historic information, for each of the data products generated by the pipeline. The Data Manager components uses a distributed, CORBA based architecture, providing a flexible and extensible object oriented framework, capable of accommodating the present and future pipeline data requirements. The Data Manager communicates with the pipeline modules, with internal and external databases, and with other NOAO systems such as the NOAO Archive and the NOAO Data Transport System.

  8. Assessment of Common and Emerging Bioinformatics Pipelines for Targeted Metagenomics

    Science.gov (United States)

    Siegwald, Léa; Touzet, Hélène; Lemoine, Yves; Hot, David

    2017-01-01

    Targeted metagenomics, also known as metagenetics, is a high-throughput sequencing application focusing on a nucleotide target in a microbiome to describe its taxonomic content. A wide range of bioinformatics pipelines are available to analyze sequencing outputs, and the choice of an appropriate tool is crucial and not trivial. No standard evaluation method exists for estimating the accuracy of a pipeline for targeted metagenomics analyses. This article proposes an evaluation protocol containing real and simulated targeted metagenomics datasets, and adequate metrics allowing us to study the impact of different variables on the biological interpretation of results. This protocol was used to compare six different bioinformatics pipelines in the basic user context: Three common ones (mothur, QIIME and BMP) based on a clustering-first approach and three emerging ones (Kraken, CLARK and One Codex) using an assignment-first approach. This study surprisingly reveals that the effect of sequencing errors has a bigger impact on the results that choosing different amplified regions. Moreover, increasing sequencing throughput increases richness overestimation, even more so for microbiota of high complexity. Finally, the choice of the reference database has a bigger impact on richness estimation for clustering-first pipelines, and on correct taxa identification for assignment-first pipelines. Using emerging assignment-first pipelines is a valid approach for targeted metagenomics analyses, with a quality of results comparable to popular clustering-first pipelines, even with an error-prone sequencing technology like Ion Torrent. However, those pipelines are highly sensitive to the quality of databases and their annotations, which makes clustering-first pipelines still the only reliable approach for studying microbiomes that are not well described. PMID:28052134

  9. Identification of metabolites of Radix Paeoniae Alba extract in rat bile, plasma and urine by ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry

    Institute of Scientific and Technical Information of China (English)

    Zheng-Wei Chen; Ling Tong; Shu-Ming Li; Dong-Xiang Li; Ying Zhang; Shui-Ping Zhou; Yong-Hong Zhu; He Sun

    2014-01-01

    Ultra-performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry (UPLC-Q-TOF/MS) was developed to identify the absorbed parent components and metabolites in rat bile, plasma and urine after oral administration of Radix Paeoniae Alba extract (RPAE). A total of 65 compounds were detected in rat bile, plasma and urine samples, including 11 parent compounds and 54 metabolites. The results indicated that glucuronidation, hydroxylation and methylation were the major metabolic pathways of the components of RPAE. Furthermore, the results of this work demonstrated that UPLC-Q-TOF/MS combined with MetaboLynx™ software and mass defect filtering (MDF) could provide unique high throughput capabilities for drug metabolism study, with excellent MS mass accuracy and enhanced MSE data acquisition. With the MSE technique, both precursor and fragment mass spectra can be simultaneously acquired by alternating between high and low collision energy during a single chromatographic run.

  10. Vulnerability of pipelines

    Energy Technology Data Exchange (ETDEWEB)

    Anon.

    2006-07-01

    Although pipelines may be damaged due to natural sources such as stress corrosion cracking (SCC) or hydrogen-induced cracking (HIC), most pipeline damages are a result of third-party interference, such as unauthorized construction in a right of way. Pipelines are also among the prime targets for sabotage because interruptions in energy distribution can render large segments of a population debilitated. The importance of protecting critical infrastructure was emphasized in this theme issue which disseminated information on vulnerability of pipelines due to third-party intrusions, both intentional and unintentional. It summarized the 10 presentations that were delivered at a pipelines security forum in Calgary, Alberta, addressing Canadian and U.S. government and industry approaches to oil and natural gas pipeline security. The opening keynote address remarked on the evolution of international terror networks, the targeting of the energy sector, and the terrorist threat and presence in Canada. Policies towards critical energy infrastructure protection (CIP) were then examined in light of these threats. A policy shift away from traditional defensive protective security towards an offensive intelligence-led strategy to forestall terrorist threats was advocated. Energy sector representatives agreed that Canada needs an effective national lead agency to provide threat assessments, alert notification, and coordination of information pertaining to CIP. It was agreed that early warning information must come from Canadian as well as U.S. sources in order to be pertinent. The conference session on information collection concentrated on defining what sort of threat information is needed by the energy sector, who should collect it and how should it be shared. It was emphasized that government leadership should coordinate threat reporting and disseminate information, set standards, and address the issues of terrorism risk insurance. Concern was raised about the lack of

  11. High performance liquid chromatography tandem mass spectrometry dual extraction method for identification of green tea catechin metabolites excreted in human urine.

    Science.gov (United States)

    Clarke, Kayleigh A; Dew, Tristan P; Watson, Rachel E B; Farrar, Mark D; Bennett, Susan; Nicolaou, Anna; Rhodes, Lesley E; Williamson, Gary

    2014-12-01

    The simultaneous analysis of free-form and conjugated flavonoids in the same sample is difficult but necessary to properly estimate their bioavailability. A method was developed to optimise the extraction of both free and conjugated forms of catechins and metabolites in a biological sample following the consumption of green tea. A double-blind randomised controlled trial was performed in which 26 volunteers consumed daily green tea and vitamin C supplements and 24 consumed a placebo for 3 months. Urine was collected for 24h at 4 separate time points (pre- and post-consumption) to confirm compliance to the supplementation and to distinguish between placebo and supplementation consumption. The urine was assessed for both free and conjugated metabolites of green tea using LC-MS(2) analysis, after a combination extraction method, which involved an ethyl acetate extraction followed by an acetonitrile protein precipitation. The combination method resulted in a good recovery of EC-O-sulphate (91±7%), EGC-O-glucuronide (94±6%), EC (95±6%), EGC (111±5%) and ethyl gallate (74±3%). A potential total of 55 catechin metabolites were investigated, and of these, 26 conjugated (with methyl, glucuronide or sulphate groups) and 3 free-form (unconjugated) compounds were identified in urine following green tea consumption. The majority of EC and EGC conjugates significantly increased post-consumption of green tea in comparison to baseline (pre-supplementation) samples. The conjugated metabolites associated with the highest peak areas were O-methyl-EC-O-sulphate and the valerolactones M6/M6'-O-sulphate. In line with previous studies, EC and EGC were only identified as conjugated derivatives, and EGCG and ECG were not found as mono-conjugated or free-forms. In summary, the method reported here provides a good recovery of catechin compounds and is appropriate for use in the assessment of flavonoid bioavailability, particularly for biological tissues that may contain endogenous

  12. Hydrolysis is the dominating in vivo metabolism pathway for arctigenin: identification of novel metabolites of arctigenin by LC/MS/MS after oral administration in rats.

    Science.gov (United States)

    Gao, Qiong; Zhang, Yufeng; Wo, Siukwan; Zuo, Zhong

    2013-04-01

    The phenylpropanoid dibenzylbutyrolactone lignan arctigenin, a key component found in Arctium lappa, or burdock, has been reported with a variety of therapeutic effects including anticancer, anti-inflammation, and antivirus effects. Using LC/MS/MS, three novel metabolites of arctigenin, namely, arctigenic acid, arctigenin-4-O'-glucuronide, and 4-O-demethylarctigenin were identified after oral administration of arctigenin in rats for the first time. Another potential metabolite of arctigenin, arctigenin-4'-O-sulfate, was identified in vitro but not in vivo. Structure of arctigenic acid, the major metabolite of arctigenin, was confirmed by 13C-NMR and 1H-NMR. Rapid hydrolysis in plasma was identified as the major metabolic pathway of arctigenin after its oral administration, with Vmax, Km, and Clint in rat plasma determined to be 2.21 ± 0.12 nmol/min/mg, 89.12 ± 9.44 µM, and 24.74 µL/min/mg, respectively. Paraoxonase 1 was further confirmed to be the enzyme responsible for arctigenin hydrolysis, with Vmax, Km, and Clint determined to be 55.39 ± 1.49 nmol/min/mg, 300.3 ± 10.86 µM, and 184.45 µL/min/mg, respectively.

  13. Instrumented Pipeline Initiative

    Energy Technology Data Exchange (ETDEWEB)

    Thomas Piro; Michael Ream

    2010-07-31

    This report summarizes technical progress achieved during the cooperative agreement between Concurrent Technologies Corporation (CTC) and U.S. Department of Energy to address the need for a for low-cost monitoring and inspection sensor system as identified in the Department of Energy (DOE) National Gas Infrastructure Research & Development (R&D) Delivery Reliability Program Roadmap.. The Instrumented Pipeline Initiative (IPI) achieved the objective by researching technologies for the monitoring of pipeline delivery integrity, through a ubiquitous network of sensors and controllers to detect and diagnose incipient defects, leaks, and failures. This report is organized by tasks as detailed in the Statement of Project Objectives (SOPO). The sections all state the objective and approach before detailing results of work.

  14. compMS2Miner: An Automatable Metabolite Identification, Visualization, and Data-Sharing R Package for High-Resolution LC-MS Data Sets.

    Science.gov (United States)

    Edmands, William M B; Petrick, Lauren; Barupal, Dinesh K; Scalbert, Augustin; Wilson, Mark J; Wickliffe, Jeffrey K; Rappaport, Stephen M

    2017-04-04

    A long-standing challenge of untargeted metabolomic profiling by ultrahigh-performance liquid chromatography-high-resolution mass spectrometry (UHPLC-HRMS) is efficient transition from unknown mass spectral features to confident metabolite annotations. The compMS(2)Miner (Comprehensive MS(2) Miner) package was developed in the R language to facilitate rapid, comprehensive feature annotation using a peak-picker-output and MS(2) data files as inputs. The number of MS(2) spectra that can be collected during a metabolomic profiling experiment far outweigh the amount of time required for pain-staking manual interpretation; therefore, a degree of software workflow autonomy is required for broad-scale metabolite annotation. CompMS(2)Miner integrates many useful tools in a single workflow for metabolite annotation and also provides a means to overview the MS(2) data with a Web application GUI compMS(2)Explorer (Comprehensive MS(2) Explorer) that also facilitates data-sharing and transparency. The automatable compMS(2)Miner workflow consists of the following steps: (i) matching unknown MS(1) features to precursor MS(2) scans, (ii) filtration of spectral noise (dynamic noise filter), (iii) generation of composite mass spectra by multiple similar spectrum signal summation and redundant/contaminant spectra removal, (iv) interpretation of possible fragment ion substructure using an internal database, (v) annotation of unknowns with chemical and spectral databases with prediction of mammalian biotransformation metabolites, wrapper functions for in silico fragmentation software, nearest neighbor chemical similarity scoring, random forest based retention time prediction, text-mining based false positive removal/true positive ranking, chemical taxonomic prediction and differential evolution based global annotation score optimization, and (vi) network graph visualizations, data curation, and sharing are made possible via the compMS(2)Explorer application. Metabolite identities and

  15. Pipeline ADC Design Methodology

    OpenAIRE

    Zhao, Hui

    2012-01-01

    Demand for high-performance analog-to-digital converter (ADC) integrated circuits (ICs) with optimal combined specifications of resolution, sampling rate and power consumption becomes dominant due to emerging applications in wireless communications, broad band transceivers, digital-intermediate frequency (IF) receivers and countless of digital devices. This research is dedicated to develop a pipeline ADC design methodology with minimum power dissipation, while keeping relatively high speed an...

  16. Pipeline ADC Design Methodology

    OpenAIRE

    Zhao, Hui

    2012-01-01

    Demand for high-performance analog-to-digital converter (ADC) integrated circuits (ICs) with optimal combined specifications of resolution, sampling rate and power consumption becomes dominant due to emerging applications in wireless communications, broad band transceivers, digital-intermediate frequency (IF) receivers and countless of digital devices. This research is dedicated to develop a pipeline ADC design methodology with minimum power dissipation, while keeping relatively high speed an...

  17. The MIS Pipeline Toolkit

    Science.gov (United States)

    Teuben, Peter J.; Pound, M. W.; Storm, S.; Mundy, L. G.; Salter, D. M.; Lee, K.; Kwon, W.; Fernandez Lopez, M.; Plunkett, A.

    2013-01-01

    A pipeline toolkit was developed to help organizing, reducing and analyzing a large number of near-identical datasets. This is a very general problem, for which many different solutions have been implemented. In this poster we present one such solution that lends itself to users of the Unix command line, using the Unix "make" utility, and adapts itself easily to observational as well as theoretical projects. Two examples are given, one from the CARMA CLASSy survey, and another from a simulated kinematic survey of early galaxy forming disks. The CLASSy survey (discussed in more detail in three accompanying posters) consists of 5 different star forming regions, observed with CARMA, each containing roughly 10-20 datasets in continuum and 3 different molecular lines, that need to be combined in final data cubes and maps. The strength of such a pipeline toolkit shows itself as new data are accumulated, the data reduction steps are improved and easily re-applied to previously taken data. For this we employed a master script that was run nightly, and collaborators submitted improved script and/or pipeline parameters that control these scripts. MIS is freely available for download.

  18. ALMA Pipeline Heuristics

    Science.gov (United States)

    Muders, D.; Boone, F.; Wyrowski, F.; Lightfoot, J.; Kosugi, G.; Wilson, C.; Davis, L.; Shepherd, D.

    2007-10-01

    The Atacama Large Millimeter Array / Atacama Compact Array (ALMA / ACA) Pipeline Heuristics system is being developed to automatically reduce data taken with the standard observing modes such as single fields, mosaics or on-the-fly maps. The goal is to make ALMA user-friendly to astronomers who are not experts in radio interferometry. The Pipeline Heuristics must capture the expert knowledge required to provide data products that can be used without further processing. The Pipeline Heuristics system is being developed as a set of Python scripts using as the data processing engines the Common Astronomy Software Applications (CASA[PY]) libraries and the ATNF Spectral Analysis Package (ASAP). The interferometry heuristics scripts currently provide an end-to-end process for the single field mode comprising flagging, initial calibration, re-flagging, re-calibration, and imaging of the target data. A Java browser provides user-friendly access to the heuristics results. The initial single-dish heuristics scripts implement automatic spectral line detection, baseline fitting and image gridding. The resulting data cubes are analyzed to detect source emission spectrally and spatially in order to calculate signal-to-noise ratios for comparison against the science goals specified by the observer.

  19. ALMA Pipeline Heuristics

    Science.gov (United States)

    Lightfoot, J.; Wyrowski, F.; Muders, D.; Boone, F.; Davis, L.; Shepherd, D.; Wilson, C.

    2006-07-01

    The ALMA (Atacama Large Millimeter Array) Pipeline Heuristics system is being developed to automatically reduce data taken with the standard observing modes. The goal is to make ALMA user-friendly to astronomers who are not experts in radio interferometry. The Pipeline Heuristics system must capture the expert knowledge required to provide data products that can be used without further processing. Observing modes to be processed by the system include single field interferometry, mosaics and single dish `on-the-fly' maps, and combinations of these modes. The data will be produced by the main ALMA array, the ALMA Compact Array (ACA) and single dish antennas. The Pipeline Heuristics system is being developed as a set of Python scripts. For interferometry these use as data processing engines the CASA/AIPS++ libraries and their bindings as CORBA objects within the ALMA Common Software (ACS). Initial development has used VLA and Plateau de Bure data sets to build and test a heuristic script capable of reducing single field data. In this paper we describe the reduction datapath and the algorithms used at each stage. Test results are presented. The path for future development is outlined.

  20. The inverse electroencephalography pipeline

    Science.gov (United States)

    Weinstein, David Michael

    The inverse electroencephalography (EEG) problem is defined as determining which regions of the brain are active based on remote measurements recorded with scalp EEG electrodes. An accurate solution to this problem would benefit both fundamental neuroscience research and clinical neuroscience applications. However, constructing accurate patient-specific inverse EEG solutions requires complex modeling, simulation, and visualization algorithms, and to date only a few systems have been developed that provide such capabilities. In this dissertation, a computational system for generating and investigating patient-specific inverse EEG solutions is introduced, and the requirements for each stage of this Inverse EEG Pipeline are defined and discussed. While the requirements of many of the stages are satisfied with existing algorithms, others have motivated research into novel modeling and simulation methods. The principal technical results of this work include novel surface-based volume modeling techniques, an efficient construction for the EEG lead field, and the Open Source release of the Inverse EEG Pipeline software for use by the bioelectric field research community. In this work, the Inverse EEG Pipeline is applied to three research problems in neurology: comparing focal and distributed source imaging algorithms; separating measurements into independent activation components for multifocal epilepsy; and localizing the cortical activity that produces the P300 effect in schizophrenia.

  1. Identification of trans,trans-2,4-decadienal metabolites in mouse and human cells using liquid chromatography-mass spectrometry.

    Science.gov (United States)

    Pan, Kao-Lu; Huang, Wei-Jan; Hsu, Ming-Hua; Lee, Hui-Ling; Liu, Huei-Ju; Cheng, Chia-Wei; Tsai, Ming-Hsien; Shen, Mei-Ya; Lin, Pinpin

    2014-10-20

    trans,trans-2,4-Decadienal (tt-DDE), a lipid peroxidation product of linolieic acid, is the most abundant aldehyde identified in cooking oil fumes and is readily detectable in food products as well as in restaurant emissions. Previously, we have reported the toxicological effects of tt-DDE in vitro and in vivo. However, the metabolic pathways of tt-DDE in vivo remain unclear. In our present study, we combined liquid chromatography-mass spectrometry with triple quadrupole and time-of-flight to identify tt-DDE metabolites in the urine of mice orally administered tt-DDE. We identified two tt-DDE metabolites, 2,4-decadienoic acid and cysteine-conjugated 2,4-decadien-1-ol, in the urine of mice gavaged with tt-DDE and in human hepatoma cell cultures. The structure of 2,4-decadienoic acid was confirmed upon comparison of its tandem mass spectrometry (MS/MS) spectrum and retention time with those of synthetic standards. The moieties of cysteine and alcohol on cysteine-conjugated 2,4-decadien-1-ol were validated by treating cell cultures with stable-isotope-labeled cysteine and 4-methylpyrazole, an alcohol dehydrogenase inhibitor. The MS/MS spectra of a cysteine standard and ionized cysteine detached from cysteine-conjugated 2,4-decadien-1-ol were identical. Two metabolic pathways for the biotransformation of tt-DDE in vivo are proposed: (i) the oxidation of tt-DDE to the corresponding carboxylic acid, 2,4-decadienoic acid, in liver cells and (ii) glutathione (GHS) conjugation, GSH breakdown, and aldehyde reduction, which generate cysteine-conjugated 2,4-decadien-1-ol in both liver and lung cells. In conclusion, this platform can be used to identify tt-DDE metabolites, and cysteine-conjugated 2,4-decadien-1-ol can serve as a biomarker for assessing exposure to tt-DDE.

  2. Metabolite signal identification in accurate mass metabolomics data with MZedDB, an interactive m/z annotation tool utilising predicted ionisation behaviour 'rules'

    Directory of Open Access Journals (Sweden)

    Snowdon Stuart

    2009-07-01

    Full Text Available Abstract Background Metabolomics experiments using Mass Spectrometry (MS technology measure the mass to charge ratio (m/z and intensity of ionised molecules in crude extracts of complex biological samples to generate high dimensional metabolite 'fingerprint' or metabolite 'profile' data. High resolution MS instruments perform routinely with a mass accuracy of Results Metabolite 'structures' harvested from publicly accessible databases were converted into a common format to generate a comprehensive archive in MZedDB. 'Rules' were derived from chemical information that allowed MZedDB to generate a list of adducts and neutral loss fragments putatively able to form for each structure and calculate, on the fly, the exact molecular weight of every potential ionisation product to provide targets for annotation searches based on accurate mass. We demonstrate that data matrices representing populations of ionisation products generated from different biological matrices contain a large proportion (sometimes > 50% of molecular isotopes, salt adducts and neutral loss fragments. Correlation analysis of ESI-MS data features confirmed the predicted relationships of m/z signals. An integrated isotope enumerator in MZedDB allowed verification of exact isotopic pattern distributions to corroborate experimental data. Conclusion We conclude that although ultra-high accurate mass instruments provide major insight into the chemical diversity of biological extracts, the facile annotation of a large proportion of signals is not possible by simple, automated query of current databases using computed molecular formulae. Parameterising MZedDB to take into account predicted ionisation behaviour and the biological source of any sample improves greatly both the frequency and accuracy of potential annotation 'hits' in ESI-MS data.

  3. Identification of selected in vitro generated phase-I metabolites of the steroidal selective androgen receptor modulator MK-0773 for doping control purposes.

    Science.gov (United States)

    Lagojda, Andreas; Kuehne, Dirk; Krug, Oliver; Thomas, Andreas; Wigger, Tina; Karst, Uwe; Schänzer, Wilhelm; Thevis, Mario

    2016-01-01

    Research into developing anabolic agents for various therapeutic purposes has been pursued for decades. As the clinical utility of anabolic-androgenic steroids has been found to be limited because of their lack of tissue selectivity and associated off-target effects, alternative drug entities have been designed and are commonly referred to as selective androgen receptor modulators (SARMs). While most of these SARMs are of nonsteroidal structure, the drug candidate MK-0773 comprises a 4-aza-steroidal nucleus. Besides the intended therapeutic use, SARMs have been found to be illicitly distributed and misused as doping agents in sport, necessitating frequently updated doping control analytical assays. As steroidal compounds reportedly undergo considerable metabolic transformations, the phase-I metabolism of MK-0773 was simulated using human liver microsomal (HLM) preparations and electrochemical conversion. Subsequently, major metabolic products were identified and characterized employing liquid chromatography-high-resolution/high- accuracy tandem mass spectrometry with electrospray (ESI) and atmospheric pressure chemical ionization (APCI) as well as nuclear magnetic resonance (NMR) spectroscopy. MK-0773 produced numerous phase-I metabolites under the chosen in vitro incubation reactions, mostly resulting from mono- and bisoxygenation of the steroid. HLM yielded at least 10 monooxygenated species, while electrochemistry-based experiments resulted predominantly in three monohydroxylated metabolites. Elemental composition data and product ion mass spectra were generated for these analytes, ESI/APCI measurements corroborated the formation of at least two N-oxygenated metabolites, and NMR data obtained from electrochemistry-derived products supported structures suggested for three monohydroxylated compounds. Hereby, the hydroxylation of the A-ring located N- bound methyl group was found to be of particular intensity. In the absence of controlled elimination studies, the

  4. Pipeline integrity : control by coatings

    Energy Technology Data Exchange (ETDEWEB)

    Khanna, A.S. [Indian Inst. of Technology, Bombay (India)

    2008-07-01

    This presentation provided background information on the history of cross-country pipelines in India. It discussed the major use of gas. The key users were described as being the power and fertilizer industries, followed by vehicles using compressed natural gas to replace liquid fuels and thereby reduce pollution. The presentation also addressed the integrity of pipelines in terms of high production, safety, and monitoring. Integrity issues of pipelines were discussed with reference to basic design, control of corrosion, and periodic health monitoring. Other topics that were outlined included integrity by corrosion control; integrity by health monitoring; coatings requirements; classification of UCC pipeline coatings; and how the pipeline integrity approach can help to achieve coatings which give design life without any failure. Surface cleanliness, coating conditions, and the relationship between temperature of Epoxy coating and the time of adhesive coating were also discussed. Last, the presentation provided the results of an audit of the HBJ pipeline conducted from 1999 to 2000. tabs., figs.

  5. Slurry pipeline technology: an overview

    Energy Technology Data Exchange (ETDEWEB)

    Chapman, Jay P. [Pipeline Systems Incorporated (PSI), Belo Horizonte, MG (Brazil); Lima, Rafael; Pinto, Daniel; Vidal, Alisson [Ausenco do Brasil Engenharia Ltda., Nova Lima, MG (Brazil). PSI Div.

    2009-12-19

    Slurry pipelines represent an economical and environmentally friendly transportation means for many solid materials. This paper provides an over-view of the technology, its evolution and current Brazilian activity. Mineral resources are increasingly moving farther away from ports, processing plants and end use points, and slurry pipelines are an important mode of solids transport. Application guidelines are discussed. State-of-the-Art technical solutions such as pipeline system simulation, pipe materials, pumps, valves, automation, telecommunications, and construction techniques that have made the technology successful are presented. A discussion of where long distant slurry pipelines fit in a picture that also includes thickened and paste materials pipe lining is included. (author)

  6. Identification and quantitation of ibogaine and an o-demethylated metabolite in brain and biological fluids using gas chromatography-mass spectrometry.

    Science.gov (United States)

    Hearn, W L; Pablo, J; Hime, G W; Mash, D C

    1995-10-01

    This report describes a sensitive method for quantitating ibogaine and a single major metabolite in biological fluids and brain tissue. We identified the metabolite as 12-hydroxy-ibogamine (12-OH-ibogamine or noribogaine) by full-scan, electron-impact gas chromatography-mass spectrometry (GC-MS). Ibogaine, 12-OH-ibogamine, and o-(methyl)-ibogaine-d3 (ibogaine-d3) internal standard were isolated by solvent extraction under basic conditions. The resulting organic extract was evaporated to dryness, and the residue was derivatized at room temperature with ethyl iodide in the presence of trimethyl anilinium hydroxide in dimethyl sulfoxide. The reaction was terminated by acidification and washed with organic solvents to remove impurities. The aqueous phase was then alkalinized and reextracted. The organic extract was concentrated and analyzed by GC-MS. Quantitation was based upon the ratios of the molecular ions at m/z 310 for ibogaine, m/z 313 for ibogaine-d3, and m/z 324 for 12-OH-ibogamine ethyl ether. The limit of detection was 5 ng/mL for both ibogaine and derivatized 12-OH-ibogamine, and limits of quantitation were between 5 and 10 ng/mL for all matrices tested. Calibration curves were linear in the range of 3-1000 ng/mL or ng/g for both analytes.

  7. Metabolite Profiling of Diverse Rice Germplasm and Identification of Conserved Metabolic Markers of Rice Roots in Response to Long-Term Mild Salinity Stress

    Directory of Open Access Journals (Sweden)

    Myung Hee Nam

    2015-09-01

    Full Text Available The sensitivity of rice to salt stress greatly depends on growth stages, organ types and cultivars. Especially, the roots of young rice seedlings are highly salt-sensitive organs that limit plant growth, even under mild soil salinity conditions. In an attempt to identify metabolic markers of rice roots responding to salt stress, metabolite profiling was performed by 1H-NMR spectroscopy in 38 rice genotypes that varied in biomass accumulation under long-term mild salinity condition. Multivariate statistical analysis showed separation of the control and salt-treated rice roots and rice genotypes with differential growth potential. By quantitative analyses of 1H-NMR data, five conserved salt-responsive metabolic markers of rice roots were identified. Sucrose, allantoin and glutamate accumulated by salt stress, whereas the levels of glutamine and alanine decreased. A positive correlation of metabolite changes with growth potential and salt tolerance of rice genotypes was observed for allantoin and glutamine. Adjustment of nitrogen metabolism in rice roots is likely to be closely related to maintain the growth potential and increase the stress tolerance of rice.

  8. Changes in Urinary Phthalate Metabolite Levels Before and After the Phthalate Contamination Event and Identification of Exposure Sources in a Cohort of Taiwanese Children.

    Science.gov (United States)

    Huang, Chian-Feng; Wang, I-Jen

    2017-08-19

    In 2011, the Taiwan Food and Drug Administration inadvertently discovered that, for decades, manufacturers had replaced expensive natural emulsifiers in food products with diethylhexyl phthalate (DEHP). We wanted to compare urinary phthalate metabolite levels of children before and after the DEHP food contamination event and identify source(s) of phthalate exposure in addition to the illegal food additives. In the present study, morning urine samples were collected from a cohort of 453 children in 2010 in Taipei. After the DEHP food contamination event, there were 200 cohort children left at follow-up in 2013. The geometric means (GMs) of urinary mono(2-ethyl-5-hydroxyhexyl) phthalate (5OH-MEHP) levels before and after the event were 9.39 and 13.34 µg/g of creatinine, respectively, with no significant difference (p = 0.093). After the DEHP food contamination event, we found that urinary phthalate metabolite levels were significantly higher in people who frequently consumed microwave-heated food and used fragrance-containing products (p event, thus, other sources must contribute to phthalate exposure in daily life. Public awareness of approaches to reducing phthalate exposure is necessary.

  9. Profiling and identification of the absorbed constituents and metabolites of schisandra lignans by ultra-performance liquid chromatography coupled to mass spectrometry.

    Science.gov (United States)

    Sun, Hui; Wu, Fangfang; Zhang, Aihua; Wei, Wenfeng; Han, Ying; Wang, Xijun

    2013-11-01

    Schisandra chinensis Baill grows wild in Russia, China, Korea and Japan, and its fruit has been found to be effective in amnesia and insomnia. It is enriched in schisandra lignans (SL) that are major components responsible for therapeutic action. However, there are no reports on the biotransformation analysis of SL. An ultra-performance liquid chromatography/electrospray-ionization high-definition mass spectrometry (UPLC-Q-TOF-HDMS) method was developed to investigate the metabolism of SL in vivo. MS was performed on a Waters Micromass high-definition system with an electrospray ionization source in positive ion mode and automated MetaboLynx software analysis with excellent MS accuracy and enhanced MS data acquisition. An improved mass defect filter (MDF) method employing both drug and core structure filter templates was applied to the processing of UPLC-Q-TOF-HDMS data for the detection and structural characterization of metabolites. In this study, 30 metabolites were detected and identified in vivo, and demethylation and hydroxylation were confirmed as the primacy metabolic pathway for SL in rat plasma. In conclusion, the presently developed methodology was suitable for biotransformation research of SL and will find wide use in metabolic studies for other herbal medicines.

  10. Oral Administration of the Japanese Traditional Medicine Keishibukuryogan-ka-yokuinin Decreases Reactive Oxygen Metabolites in Rat Plasma: Identification of Chemical Constituents Contributing to Antioxidant Activity

    Directory of Open Access Journals (Sweden)

    Yosuke Matsubara

    2017-02-01

    Full Text Available Insufficient detoxification and/or overproduction of reactive oxygen species (ROS induce cellular and tissue damage, and generated reactive oxygen metabolites become exacerbating factors of dermatitis. Keishibukuryogan-ka-yokuinin (KBGY is a traditional Japanese medicine prescribed to treat dermatitis such as acne vulgaris. Our aim was to verify the antioxidant properties of KBGY, and identify its active constituents by blood pharmacokinetic techniques. Chemical constituents were quantified in extracts of KBGY, crude components, and the plasma of rats treated with a single oral administration of KBGY. Twenty-three KBGY compounds were detected in plasma, including gallic acid, prunasin, paeoniflorin, and azelaic acid, which have been reported to be effective for inflammation. KBGY decreased level of the diacron-reactive oxygen metabolites (d-ROMs in plasma. ROS-scavenging and lipid hydroperoxide (LPO generation assays revealed that gallic acid, 3-O-methylgallic acid, (+-catechin, and lariciresinol possess strong antioxidant activities. Gallic acid was active at a similar concentration to the maximum plasma concentration, therefore, our findings indicate that gallic acid is an important active constituent contributing to the antioxidant effects of KBGY. KBGY and its active constituents may improve redox imbalances induced by oxidative stress as an optional treatment for skin diseases.

  11. INTERNAL REPAIR OF PIPELINES

    Energy Technology Data Exchange (ETDEWEB)

    Bill Bruce; Nancy Porter; George Ritter; Matt Boring; Mark Lozev; Ian Harris; Bill Mohr; Dennis Harwig; Robin Gordon; Chris Neary; Mike Sullivan

    2005-07-20

    The two broad categories of fiber-reinforced composite liner repair and deposited weld metal repair technologies were reviewed and evaluated for potential application for internal repair of gas transmission pipelines. Both are used to some extent for other applications and could be further developed for internal, local, structural repair of gas transmission pipelines. Principal conclusions from a survey of natural gas transmission industry pipeline operators can be summarized in terms of the following performance requirements for internal repair: (1) Use of internal repair is most attractive for river crossings, under other bodies of water, in difficult soil conditions, under highways, under congested intersections, and under railway crossings. (2) Internal pipe repair offers a strong potential advantage to the high cost of horizontal direct drilling when a new bore must be created to solve a leak or other problem. (3) Typical travel distances can be divided into three distinct groups: up to 305 m (1,000 ft.); between 305 m and 610 m (1,000 ft. and 2,000 ft.); and beyond 914 m (3,000 ft.). All three groups require pig-based systems. A despooled umbilical system would suffice for the first two groups which represents 81% of survey respondents. The third group would require an onboard self-contained power unit for propulsion and welding/liner repair energy needs. (4) The most common size range for 80% to 90% of operators surveyed is 508 mm (20 in.) to 762 mm (30 in.), with 95% using 558.8 mm (22 in.) pipe. Evaluation trials were conducted on pipe sections with simulated corrosion damage repaired with glass fiber-reinforced composite liners, carbon fiber-reinforced composite liners, and weld deposition. Additional un-repaired pipe sections were evaluated in the virgin condition and with simulated damage. Hydrostatic failure pressures for pipe sections repaired with glass fiber-reinforced composite liner were only marginally greater than that of pipe sections without

  12. Oxygen radical induced fluorescence in proteins; identification of the fluorescent tryptophan metabolite, N-formyl kynurenine, as a biological index of radical damage.

    Science.gov (United States)

    Griffiths, H R; Lunec, J; Blake, D R

    1992-06-01

    The effect of oxygen derived free radicals (OFR) on aromatic and sulphur containing amino acids has been investigated, both in their free form and within protein backbones. Aerated amino acids and proteins in solution were exposed to three discrete OFR generating systems; (1) gamma radiation in the presence or absence of formate (2) photolysis by UV light at 254 and 366 nm, and (3) site specific modification by H2O2 in the presence of CuII ions.A sensitive reverse-phase HPLC technique with dual detection systems (UV absorbance and fluorescence monitoring) was developed to analyse the products of amino acid oxidation. OFR denatured amino acids were chromatographed by this procedure, and all radical species generated, with the exception of the superoxide anion, resulted in the formation of identifiable fluorescent metabolites of tryptophan, kynurenines. The identity of peaks was confimed by spiking with authentic material and scanning absorption spectroscopy. After complete proteolytic hydrolysis, OFR treated proteins were also analysed by this technique; again the dose dependent production of kynurenines was detected in IgG,γ lens crystallins and albumin. Bityrosine was not detected in any of the proteins studied using this procedure, however, several novel unidentified fluorophores were detected in proteolytic hydrolysates, possibly the product of two different amino acid radicals.Immunoglobulin G isolated from the sera of normals and rheumatoid arthritis (RA) patients was examined for the presence of one specific tryptophan metabolite, N-formyl kynurenine. Significantly elevated levels of this metabolite were detected in rheumatoid sera, suggesting increased OFR activity in RA.These results have demonstrated firstly, that specific oxidised products of amino acids are retained in the protein backbone after exposure to OFR generating systems. Secondly, in aerated solution, oxidised tryptophan residues confer the major new visible fluorescence in non-haem proteins

  13. Kvitebjoern gas pipeline repair - baptism of remote pipeline repair system

    Energy Technology Data Exchange (ETDEWEB)

    Gjertveit, Erling

    2010-07-01

    On the 1st of November 2007, severe anchor damage was discovered on the 30 inch Kvitebjoern gas export pipeline. The damage constituted a localised dent and a 17deg buckle, but no leakage. Statoil has invested in building an effective repair contingency structure for the large pipeline network on the Norwegian Continental shelf, with particular focus on the large gas export pipelines. The repair method for the Kvitebjoern pipeline was remotely operated using two Morgrip couplings and a spool. The installation used the purpose built Pipeline Repair System stored at Killingoey and couplings produced and tested back in 2005. This presentation will cover the initial damage investigations, the temporary operational phase, the repair preparations, the actual repair and lessons learned. (Author)

  14. Electrosynthesis methods and approaches for the preparative production of metabolites from parent drugs

    NARCIS (Netherlands)

    Gül, Turan; Bischoff, Rainer; Permentier, Hjalmar

    2015-01-01

    Identification of potentially toxic metabolites is important for drug discovery and development. Synthesis of drug metabolites is typically performed by organic synthesis or enzymatic methods, but is not always straightforward. Electrochemical (EC) methods are increasingly used to study drug oxidati

  15. Secondary metabolite profiling of Alternaria dauci, A. porri, A. solani, and A. tomatophila

    DEFF Research Database (Denmark)

    Andersen, Birgitte; Dongo, Anita; Pryor, Barry M.

    2008-01-01

    Chemotaxonomy (secondary metabolite profiling) has been shown to be of great value in the classification and differentiation in Ascomycota. However, few studies have investigated the use of metabolite production for classification and identification purposes of plant pathogenic Alternaria species...

  16. Combined analysis of transcriptome and metabolite data reveals extensive differences between black and brown nearly-isogenic soybean (Glycine max seed coats enabling the identification of pigment isogenes

    Directory of Open Access Journals (Sweden)

    Arnason John T

    2011-07-01

    Full Text Available Abstract Background The R locus controls the color of pigmented soybean (Glycine max seeds. However information about its control over seed coat biochemistry and gene expressions remains limited. The seed coats of nearly-isogenic black (iRT and brown (irT soybean (Glycine max were known to differ by the presence or absence of anthocyanins, respectively, with genes for only a single enzyme (anthocyanidin synthase found to be differentially expressed between isolines. We recently identified and characterized a UDP-glycose:flavonoid-3-O-glycosyltransferase (UGT78K1 from the seed coat of black (iRT soybean with the aim to engineer seed coat color by suppression of an anthocyanin-specific gene. However, it remained to be investigated whether UGT78K1 was overexpressed with anthocyanin biosynthesis in the black (iRT seed coat compared to the nearly-isogenic brown (irT tissue. In this study, we performed a combined analysis of transcriptome and metabolite data to elucidate the control of the R locus over seed coat biochemistry and to identify pigment biosynthesis genes. Two differentially expressed late-stage anthocyanin biosynthesis isogenes were further characterized, as they may serve as useful targets for the manipulation of soybean grain color while minimizing the potential for unintended effects on the plant system. Results Metabolite composition differences were found to not be limited to anthocyanins, with specific proanthocyanidins, isoflavones, and phenylpropanoids present exclusively in the black (iRT or the brown (irT seed coat. A global analysis of gene expressions identified UGT78K1 and 19 other anthocyanin, (isoflavonoid, and phenylpropanoid isogenes to be differentially expressed between isolines. A combined analysis of metabolite and gene expression data enabled the assignment of putative functions to biosynthesis and transport isogenes. The recombinant enzymes of two genes were validated to catalyze late-stage steps in anthocyanin

  17. Separation and identification of Se-methylselenogalactosamine - a new metabolite in basal human urine - by HPLC-ICP-MS and CE-nano-ESI-(MS)(2)

    DEFF Research Database (Denmark)

    Bendahl, L.; Gammelgaard, Bente

    2004-01-01

    Three minor metabolites were isolated from human urine. Two of these were identified by nano electrospray ionisation mass spectrometry (nESI-MS) as Se-methylseleno-N-acetylglucosamine and Se-methylselenogalactosamine, respectively. A human urine pool was lyophilised and reconstituted in methanol....... It was not possible to identify this selenium compound on basis of the available data. The selenium compound in the second fraction showed co-elution with a Se-methylseleno-N-acetylglucosamine standard. The identity of this compound was verified by nESI-MS after further purification by size exclusion chromatography....... The third fraction was further purified by ion-pair and anion exchange chromatography, reconstituted and subjected to CE-nESI-MS. The m/z of the compound was 258 and ( MS) 2 resulted in a fragment at m/z 162, corresponding to loss of methylselenium. This indicated that the structure of the compound was Se...

  18. Nonanthocyanin secondary metabolites of black raspberry (Rubus occidentalis L.) fruits: identification by HPLC-DAD, NMR, HPLC-ESI-MS, and ESI-MS/MS analyses.

    Science.gov (United States)

    Paudel, Liladhar; Wyzgoski, Faith J; Scheerens, Joseph C; Chanon, Ann M; Reese, R Neil; Smiljanic, Danijela; Wesdemiotis, Chrys; Blakeslee, Joshua J; Riedl, Kenneth M; Rinaldi, Peter L

    2013-12-11

    Nonanthocyanin secondary metabolites potentially contributing to the antiproliferative bioactivity of black raspberry ( Rubus occidentalis L.) fruits were extracted in ethyl acetate and isolated by semipreparative and analytical HPLC and analyzed by NMR, HPLC-ESI-MS, and ESI-MS/MS techniques. Here we present complete and partial structures of a variety of the chemical entities such as quercetin 3-glucoside, quercetin 3-rutinoside, myricetin glucoside, dihydrokaempferol glucoside, benzoic acid β-d-glucopyranosyl ester, 3,4-dihydroxybenzoic acid, epicatechin, caffeic acid, p-coumaric acid, p-coumaryl glucoside, p-coumaryl sugar ester, ellagic acid, methyl ellagic acid acetylpentose, methyl ellagic acid valerylpentose, trans-piceid, phloretin glucoside (phloridzin), dihydrosinapic acid, salicylic acid β-d-glucopyranosyl ester, a salicylic acid derivative without attached sugar, p-alkylphenyl glucoside, and a citric acid derivative. To our knowledge, 15 of these compounds were not previously reported in black raspberry fruits.

  19. Transportation of coal by pipeline

    Energy Technology Data Exchange (ETDEWEB)

    Round, G.F.

    1982-01-01

    Discusses Canada's coal resources, technology of long distance coal slurry pipelines, existing and planned coal slurry pipelines, their economics, liquid carbon dioxide, methanol and crude oil instead of water as carrier fluid, and coal slurry research in Canada.

  20. PHOTOMETRYPIPELINE: An automated pipeline for calibrated photometry

    Science.gov (United States)

    Mommert, M.

    2017-01-01

    PHOTOMETRYPIPELINE (PP) is an automated pipeline that produces calibrated photometry from imaging data through image registration, aperture photometry, photometric calibration, and target identification with only minimal human interaction. PP utilizes the widely used Source Extractor software for source identification and aperture photometry; SCAMP is used for image registration. Both image registration and photometric calibration are based on matching field stars with star catalogs, requiring catalog coverage of the respective field. A number of different astrometric and photometric catalogs can be queried online. Relying on a sufficient number of background stars for image registration and photometric calibration, PP is well-suited to analyze data from small to medium-sized telescopes. Calibrated magnitudes obtained by PP are typically accurate within ≤0.03 mag and astrometric accuracies are of the order of 0.3 arcsec relative to the catalogs used in the registration. The pipeline consists of an open-source software suite written in Python 2.7, can be run on Unix-based systems on a simple desktop machine, and is capable of realtime data analysis. PP has been developed for observations of moving targets, but can be used for analyzing point source observations of any kind.

  1. Analyses and application of the magnetic field at girth welds in pipelines

    Science.gov (United States)

    Huang, Xinjing; Chen, Shili; Guo, Shixu; Zhao, Wei; Zhang, Yu; Jin, Shijiu

    2013-11-01

    This paper proposes a novel method of utilizing weld identification to improve the positioning accuracy of an in-pipe detector in pipelines. The distributions of the magnetic field inside a single pipe are analysed using the equivalent magnetic charge method. Then the causes and characteristics of abnormal magnetic fields near the welds in the pipelines when pipes are welded together are discussed. A spherical carrier equipped with a magnetic sensor is designed and is used to measure the magnetic field inside an annular experimental pipeline when the carrier is pushed forward by the fluid in the pipeline and is rolling along the pipeline. Theory and experimental research show that there are very obvious abnormalities of the magnetic field at the girth welds in the pipelines. The abnormal magnetic field near the welds can be remarkably enhanced and accurately located using the signal enhancement method of continuous wavelet transformation and the peak detection method based on quadratic polynomial fitting respectively, thus enabling the identification and location of the welds. Different approaches are adopted to process magnetic field signals of different intensities in the pipelines in different directions. Finally, by considering construction information on the pipelines recorded previously, the positioning error is kept to less than 5 cm.

  2. INTERNAL REPAIR OF PIPELINES

    Energy Technology Data Exchange (ETDEWEB)

    Robin Gordon; Bill Bruce; Ian Harris; Dennis Harwig; George Ritter; Bill Mohr; Matt Boring; Nancy Porter; Mike Sullivan; Chris Neary

    2004-08-17

    The two broad categories of fiber-reinforced composite liner repair and deposited weld metal repair technologies were reviewed and evaluated for potential application for internal repair of gas transmission pipelines. Both are used to some extent for other applications and could be further developed for internal, local, structural repair of gas transmission pipelines. Principal conclusions from a survey of natural gas transmission industry pipeline operators can be summarized in terms of the following performance requirements for internal repair: (1) Use of internal repair is most attractive for river crossings, under other bodies of water, in difficult soil conditions, under highways, under congested intersections, and under railway. (2) Internal pipe repair offers a strong potential advantage to the high cost of horizontal direct drilling when a new bore must be created to solve a leak or other problem. (3) Typical travel distances can be divided into three distinct groups: up to 305 m (1,000 ft.); between 305 m and 610 m (1,000 ft. and 2,000 ft.); and beyond 914 m (3,000 ft.). All three groups require pig-based systems. A despooled umbilical system would suffice for the first two groups which represents 81% of survey respondents. The third group would require an onboard self-contained power unit for propulsion and welding/liner repair energy needs. (4) The most common size range for 80% to 90% of operators surveyed is 508 mm (20 in.) to 762 mm (30 in.), with 95% using 558.8 mm (22 in.) pipe. Evaluation trials were conducted on pipe sections with simulated corrosion damage repaired with glass fiber-reinforced composite liners, carbon fiber-reinforced composite liners, and weld deposition. Additional un-repaired pipe sections were evaluated in the virgin condition and with simulated damage. Hydrostatic failure pressures for pipe sections repaired with glass fiber-reinforced composite liner were only marginally greater than that of pipe sections without liners

  3. INTERNAL REPAIR OF PIPELINES

    Energy Technology Data Exchange (ETDEWEB)

    Robin Gordon; Bill Bruce; Ian Harris; Dennis Harwig; George Ritter; Bill Mohr; Matt Boring; Nancy Porter; Mike Sullivan; Chris Neary

    2004-12-31

    The two broad categories of fiber-reinforced composite liner repair and deposited weld metal repair technologies were reviewed and evaluated for potential application for internal repair of gas transmission pipelines. Both are used to some extent for other applications and could be further developed for internal, local, structural repair of gas transmission pipelines. Principal conclusions from a survey of natural gas transmission industry pipeline operators can be summarized in terms of the following performance requirements for internal repair: (1) Use of internal repair is most attractive for river crossings, under other bodies of water, in difficult soil conditions, under highways, under congested intersections, and under railway crossings. (2) Internal pipe repair offers a strong potential advantage to the high cost of horizontal direct drilling when a new bore must be created to solve a leak or other problem. (3) Typical travel distances can be divided into three distinct groups: up to 305 m (1,000 ft.); between 305 m and 610 m (1,000 ft. and 2,000 ft.); and beyond 914 m (3,000 ft.). All three groups require pig-based systems. A despooled umbilical system would suffice for the first two groups which represents 81% of survey respondents. The third group would require an onboard self-contained power unit for propulsion and welding/liner repair energy needs. (4) The most common size range for 80% to 90% of operators surveyed is 508 mm (20 in.) to 762 mm (30 in.), with 95% using 558.8 mm (22 in.) pipe. Evaluation trials were conducted on pipe sections with simulated corrosion damage repaired with glass fiber-reinforced composite liners, carbon fiber-reinforced composite liners, and weld deposition. Additional un-repaired pipe sections were evaluated in the virgin condition and with simulated damage. Hydrostatic failure pressures for pipe sections repaired with glass fiber-reinforced composite liner were only marginally greater than that of pipe sections without

  4. INTERNAL REPAIR OF PIPELINES

    Energy Technology Data Exchange (ETDEWEB)

    Robin Gordon; Bill Bruce; Ian Harris; Dennis Harwig; Nancy Porter; Mike Sullivan; Chris Neary

    2004-04-12

    The two broad categories of deposited weld metal repair and fiber-reinforced composite liner repair technologies were reviewed for potential application for internal repair of gas transmission pipelines. Both are used to some extent for other applications and could be further developed for internal, local, structural repair of gas transmission pipelines. Preliminary test programs were developed for both deposited weld metal repair and for fiber-reinforced composite liner repair. Evaluation trials have been conducted using a modified fiber-reinforced composite liner provided by RolaTube and pipe sections without liners. All pipe section specimens failed in areas of simulated damage. Pipe sections containing fiber-reinforced composite liners failed at pressures marginally greater than the pipe sections without liners. The next step is to evaluate a liner material with a modulus of elasticity approximately 95% of the modulus of elasticity for steel. Preliminary welding parameters were developed for deposited weld metal repair in preparation of the receipt of Pacific Gas & Electric's internal pipeline welding repair system (that was designed specifically for 559 mm (22 in.) diameter pipe) and the receipt of 559 mm (22 in.) pipe sections from Panhandle Eastern. The next steps are to transfer welding parameters to the PG&E system and to pressure test repaired pipe sections to failure. A survey of pipeline operators was conducted to better understand the needs and performance requirements of the natural gas transmission industry regarding internal repair. Completed surveys contained the following principal conclusions: (1) Use of internal weld repair is most attractive for river crossings, under other bodies of water, in difficult soil conditions, under highways, under congested intersections, and under railway crossings. (2) Internal pipe repair offers a strong potential advantage to the high cost of horizontal direct drilling (HDD) when a new bore must be created

  5. Pipeline risk assessment

    Energy Technology Data Exchange (ETDEWEB)

    Kariyawasam, S. [TransCanada PipeLines Ltd., Calgary, AB (Canada); Weir, D. [Enbridge Pipelines Inc., Calgary, AB (Canada)] (comps.)

    2009-07-01

    Risk assessments and risk analysis are system-wide activities that include site-specific risk and reliability-based decision-making, implementation, and monitoring. This working group discussed the risk management process in the pipeline industry, including reliability-based integrity management and risk control processes. Attendants at the group discussed reliability-based decision support and performance measurements designed to support corporate risk management policies. New developments and technologies designed to optimize risk management procedures were also presented. The group was divided into 3 sessions: (1) current practice, strengths and limitations of system-wide risk assessments for facility assets; (2) accounting for uncertainties to assure safety; and (3) reliability based excavation repair criteria and removing potentially unsafe corrosion defects. Presentations of risk assessment procedures used at various companies were given. The role of regulators, best practices, and effective networking environments in ensuring the success of risk assessment policies was discussed. Risk assessment models were also reviewed.

  6. Maglev crude oil pipeline

    Science.gov (United States)

    Knolle, Ernst G.

    1994-05-01

    This maglev crude oil pipeline consists of two conduits guiding an endless stream of long containers. One conduit carries loaded containers and the other empty returns. The containers are levitated by permanent magnets in repulsion and propelled by stationary linear induction motors. The containers are linked to each other in a manner that allows them, while in continuous motion, to be folded into side by side position at loading and unloading points. This folding causes a speed reduction in proportion to the ratio of container diameter to container length. While in side by side position, containers are opened at their ends to be filled or emptied. Container size and speed are elected to produce a desired carrying capacity.

  7. Isolation and identification of novel genes involved in artemisinin production from flowers of Artemisia annua using suppression subtractive hybridization and metabolite analysis.

    Science.gov (United States)

    Liu, Shuoqian; Tian, Na; Li, Juan; Huang, Jianan; Liu, Zhonghua

    2009-11-01

    Malaria is a global health problem that threatens 300-500 million people and kills more than one million people annually. Artemisinin is highly effective against multidrug-resistant Plasmodium falciparum and it has been widely used as part of the artemisinin-based combination therapies against malaria. To elucidate the biosynthetic pathway of artemisinin and to clone related genes in Artemisia annua, differentially expressed genes between blooming flowers and flower buds were isolated and characterized by a combined approach of suppression subtractive hybridization (SSH) and metabolite analysis. A total of 350 cDNA clones from a subtractive cDNA library were randomly picked, sequenced and analyzed and 253 high-quality sequences were obtained. BLASTX comparisons indicated that about 9.9 % of the clones encoded enzymes involved in isoprenoid (including artemisinin) biosynthesis. The expression of 4 gene transcripts involved in artemisinin biosynthesis was examined by RT-PCR and the results confirmed the higher expression of these transcripts in blooming flowers than in flower buds. In addition, 2 putative transcript factors transparenta testa glabra 1 (TTG1) and ENHANCER OF GLABRA3 (GL3), which promote trichome initiation, were presented in the library. Finally, this study demonstrated that the increase of expression level of the putative TTG1 gene correlated with the improvement of glandular trichome density and artemisinin production in A. annua leaves. The subtractive cDNA library described in the present study provides important candidate genes for future research in order to increase the artemisinin content in A. annua.

  8. Kernel-Based, Partial Least Squares Quantitative Structure-Retention Relationship Model for UPLC Retention Time Prediction: A Useful Tool for Metabolite Identification.

    Science.gov (United States)

    Falchi, Federico; Bertozzi, Sine Mandrup; Ottonello, Giuliana; Ruda, Gian Filippo; Colombano, Giampiero; Fiorelli, Claudio; Martucci, Cataldo; Bertorelli, Rosalia; Scarpelli, Rita; Cavalli, Andrea; Bandiera, Tiziano; Armirotti, Andrea

    2016-10-04

    We propose a new QSRR model based on a Kernel-based partial least-squares method for predicting UPLC retention times in reversed phase mode. The model was built using a combination of classical (physicochemical and topological) and nonclassical (fingerprints) molecular descriptors of 1383 compounds, encompassing different chemical classes and structures and their accurately measured retention time values. Following a random splitting of the data set into a training and a test set, we tested the ability of the model to predict the retention time of all the compounds. The best predicted/experimental R(2) value was higher than 0.86, while the best Q(2) value we observed was close to 0.84. A comparison of our model with traditional and simpler MLR and PLS regression models shows that KPLS better performs in term of correlation (R(2)), prediction (Q(2)), and support to MetID peak assignment. The KPLS model succeeded in two real-life MetID tasks by correctly predicting elution order of Phase I metabolites, including isomeric monohydroxylated compounds. We also show in this paper that the model's predictive power can be extended to different gradient profiles, by simple mathematical extrapolation using a known equation, thus offering very broad flexibility. Moreover, the current study includes a deep investigation of different types of chemical descriptors used to build the structure-retention relationship.

  9. Northern pipelines : challenges and needs

    Energy Technology Data Exchange (ETDEWEB)

    Dean, D.; Brownie, D. [ProLog Canada Inc., Calgary, AB (Canada); Fafara, R. [TransCanada PipeLines Ltd., Calgary, AB (Canada)

    2007-07-01

    Working Group 10 presented experiences acquired from the operation of pipeline systems in a northern environment. There are currently 3 pipelines operating north of 60, notably the Shiha gas pipeline near Fort Liard, the Ikhil gas pipeline in Inuvik and the Norman Wells oil pipeline. Each has its unique commissioning, operating and maintenance challenges, as well as specific training and logistical support requirements for the use of in-line inspection tools and other forms of integrity assessment. The effectiveness of cathodic protection systems in a permafrost northern environment was also discussed. It was noted that the delay of the Mackenzie Gas Pipeline Project by two to three years due to joint regulatory review may lead to resource constraints for the project as well as competition for already scarce human resources. The issue of a potential timing conflict with the Alaskan Pipeline Project was also addressed as well as land use issues for routing of supply roads. Integrity monitoring and assessment issues were outlined with reference to pipe soil interaction monitoring in discontinuous permafrost; south facing denuded slope stability; base lining projects; and reclamation issues. It was noted that automatic welding and inspection will increase productivity, while reducing the need for manual labour. In response to anticipated training needs, companies are planning to involve and train Aboriginal labour and will provide camp living conditions that will attract labour. tabs., figs.

  10. Pipeline clean-up : speed, environment drive pipelining equipment

    Energy Technology Data Exchange (ETDEWEB)

    Budd, G.

    2004-08-01

    Horizontal drilling technology is the single most important enhanced oil recovery technology which has resulted in a significant increase in pipeline utilization. Pipeline operators such as Calgary-based Denim Pipeline Construction Ltd. are responding by using the latest equipment, including excavation equipment, to avoid maintenance delays and downtime. The sales of Denim's horizontal pipe bending equipment have increased due to their attention to worker safety. Denim's horizontal bending machine does not require as much technical support, plus it is faster to install and speeds up production. The machine consists of 3 hydraulic jacks that move on a horizontal plate. Curved dies can be modified to accommodate various diameters of pipe. The bending operation is performed very near to the ground, thereby significantly reducing the risk of pipe injury. Environmental damage is minimized through the use of mechanized mulching which has replaced burning of unwanted trees and brush to clean for pipelines. 1 fig.

  11. RUSSIA AND ITS PIPELINE WEAPON

    Directory of Open Access Journals (Sweden)

    FODOR Cosmin

    2010-12-01

    Full Text Available In this paper we intend to present the new power which is given to Russia upon EU due to her great natural resources and due to her control upon pipelines. Now Moscow can exert influence upon countries in Europe not through its revolutionary zeal and its tanks and army, but through its resources. And she knows how to use them and how make the EU dependent on her will: this is a new geopolitics, a 21-th century geopolitics, which is centered upon the control of gas pipelines in Central Asian states and upon EU states great dependence on Russian pipeline system.

  12. Natural gas pipeline technology overview.

    Energy Technology Data Exchange (ETDEWEB)

    Folga, S. M.; Decision and Information Sciences

    2007-11-01

    The United States relies on natural gas for one-quarter of its energy needs. In 2001 alone, the nation consumed 21.5 trillion cubic feet of natural gas. A large portion of natural gas pipeline capacity within the United States is directed from major production areas in Texas and Louisiana, Wyoming, and other states to markets in the western, eastern, and midwestern regions of the country. In the past 10 years, increasing levels of gas from Canada have also been brought into these markets (EIA 2007). The United States has several major natural gas production basins and an extensive natural gas pipeline network, with almost 95% of U.S. natural gas imports coming from Canada. At present, the gas pipeline infrastructure is more developed between Canada and the United States than between Mexico and the United States. Gas flows from Canada to the United States through several major pipelines feeding U.S. markets in the Midwest, Northeast, Pacific Northwest, and California. Some key examples are the Alliance Pipeline, the Northern Border Pipeline, the Maritimes & Northeast Pipeline, the TransCanada Pipeline System, and Westcoast Energy pipelines. Major connections join Texas and northeastern Mexico, with additional connections to Arizona and between California and Baja California, Mexico (INGAA 2007). Of the natural gas consumed in the United States, 85% is produced domestically. Figure 1.1-1 shows the complex North American natural gas network. The pipeline transmission system--the 'interstate highway' for natural gas--consists of 180,000 miles of high-strength steel pipe varying in diameter, normally between 30 and 36 inches in diameter. The primary function of the transmission pipeline company is to move huge amounts of natural gas thousands of miles from producing regions to local natural gas utility delivery points. These delivery points, called 'city gate stations', are usually owned by distribution companies, although some are owned by

  13. Effort problem of chemical pipelines

    Energy Technology Data Exchange (ETDEWEB)

    Okrajni, J.; Ciesla, M.; Mutwil, K. [Silesian Technical University, Katowice (Poland)

    1998-12-31

    The problem of the technical state assessment of the chemical pipelines working under mechanical and thermal loading has been shown in the paper. The pipelines effort after the long time operating period has been analysed. Material geometrical and loading conditions of the crack initiation and crack growth process in the chosen object has been discussed. Areas of the maximal effort have been determined. The material structure charges after the long time operating period have been described. Mechanisms of the crack initiation and crack growth in the pipeline elements have been analysed and mutual relations between the chemical and mechanical influences have been shown. (orig.) 16 refs.

  14. Liquid chromatography tandem mass spectrometry method for the quantitation of mycophenolate mofetil in human plasma: Application to a bioequivalence study and metabolite identification.

    Science.gov (United States)

    Partani, Pankaj; Verma, Saurabh Manaswita; Monif, Tausif

    2015-10-01

    We established a sensitive, selective, and rapid analytical method for the quantitation and pharmacokinetic investigation of mycophenolate mofetil in human plasma. To our knowledge, this is the first method that characterizes presence of mycophenolate mofetil glucuronide in clinical samples through tandem mass spectrometry detection and resolves mycophenolate mofetil from its glucuronide metabolite. Liquid chromatography coupled to tandem mass spectrometry detection in positive ion mode was selected to provide optimal selectivity and sensitivity. Due to the ionizable characteristics of the mycophenolate mofetil, a mixed-mode cation-exchange disposable extraction cartridge was prudently chosen. The chromatographic separation was achieved on Luna(®) C18(2) (100×4.60 mm) column using mobile phase consisting of a mixture of 1±0.05 mM ammonium formate in water, titrated to pH 3.1±0.1 with formic acid, and methanol (20:80, v/v), at a flow rate of 0.7 mL/min. The detection was led at m/z ratios of 434.4→ 114.2 and 438.4→ 118.3, for mycophenolate mofetil and mycophenolate mofetil-D4, respectively. The developed method was linear between 40.2-4986.0 pg/mL. All validation parameters were within the defined limits. The validated method was then successfully applied for the evaluation of bioequivalence parameters of mycophenolate mofetil after an oral administration of 500 mg mycophenolate mofetil tablet to healthy male Indian volunteers.

  15. 75 FR 72877 - Pipeline Safety: Updates to Pipeline and Liquefied Natural Gas Reporting Requirements

    Science.gov (United States)

    2010-11-26

    ... Safety: Updates to Pipeline and Liquefied Natural Gas Reporting Requirements; Final Rule #0;#0;Federal... to Pipeline and Liquefied Natural Gas Reporting Requirements AGENCY: Pipeline and Hazardous Materials... collections from operators of natural gas pipelines, hazardous liquid pipelines, and liquefied natural......

  16. Logistics aspects of petroleum pipeline operations

    Directory of Open Access Journals (Sweden)

    W. J. Pienaar

    2010-11-01

    Full Text Available The paper identifies, assesses and describes the logistics aspects of the commercial operation of petroleum pipelines. The nature of petroleum-product supply chains, in which pipelines play a role, is outlined and the types of petroleum pipeline systems are described. An outline is presented of the nature of the logistics activities of petroleum pipeline operations. The reasons for the cost efficiency of petroleum pipeline operations are given. The relative modal service effectiveness of petroleum pipeline transport, based on the most pertinent service performance measures, is offered. The segments in the petroleum-products supply chain where pipelines can play an efficient and effective role are identified.

  17. Pipeline integrity handbook risk management and evaluation

    CERN Document Server

    Singh, Ramesh

    2013-01-01

    Based on over 40 years of experience in the field, Ramesh Singh goes beyond corrosion control, providing techniques for addressing present and future integrity issues. Pipeline Integrity Handbook provides pipeline engineers with the tools to evaluate and inspect pipelines, safeguard the life cycle of their pipeline asset and ensure that they are optimizing delivery and capability. Presented in easy-to-use, step-by-step order, Pipeline Integrity Handbook is a quick reference for day-to-day use in identifying key pipeline degradation mechanisms and threats to pipeline integrity. The book begins

  18. PIPELINES AS COMMUNICATION NETWORK LINKS

    Energy Technology Data Exchange (ETDEWEB)

    Kelvin T. Erickson; Ann Miller; E. Keith Stanek; C.H. Wu; Shari Dunn-Norman

    2005-03-14

    This report presents the results of an investigation into two methods of using the natural gas pipeline as a communication medium. The work addressed the need to develop secure system monitoring and control techniques between the field and control centers and to robotic devices in the pipeline. In the first method, the pipeline was treated as a microwave waveguide. In the second method, the pipe was treated as a leaky feeder or a multi-ground neutral and the signal was directly injected onto the metal pipe. These methods were tested on existing pipeline loops at UMR and Batelle. The results reported in this report indicate the feasibility of both methods. In addition, a few suitable communication link protocols for this network were analyzed.

  19. Nondestructive characterization of pipeline materials

    Science.gov (United States)

    Engle, Brady J.; Smart, Lucinda J.; Bond, Leonard J.

    2015-03-01

    There is a growing need to quantitatively and nondestructively evaluate the strength and toughness properties of pipeline steels, particularly in aging pipeline infrastructure. These strength and toughness properties, namely yield strength, tensile strength, transition temperature, and toughness, are essential for determining the safe operating pressure of the pipelines. For some older pipelines crucial information can be unknown, which makes determining the pressure rating difficult. Current inspection techniques address some of these issues, but they are not comprehensive. This paper will briefly discuss current inspection techniques and relevant literature for relating nondestructive measurements to key strength and toughness properties. A project is in progress to provide new in-trench tools that will give strength properties without the need for sample removal and destructive testing. Preliminary experimental ultrasonic methods and measurements will be presented, including velocity, attenuation, and backscatter measurements.

  20. Secondary metabolite gene clusters in the entomopathogen fungus Metarhizium anisopliae: genome identification and patterns of expression in a cuticle infection model

    Directory of Open Access Journals (Sweden)

    Nicolau Sbaraini

    2016-10-01

    Full Text Available Abstract Background The described species from the Metarhizium genus are cosmopolitan fungi that infect arthropod hosts. Interestingly, while some species infect a wide range of hosts (host-generalists, other species infect only a few arthropods (host-specialists. This singular evolutionary trait permits unique comparisons to determine how pathogens and virulence determinants emerge. Among the several virulence determinants that have been described, secondary metabolites (SMs are suggested to play essential roles during fungal infection. Despite progress in the study of pathogen-host relationships, the majority of genes related to SM production in Metarhizium spp. are uncharacterized, and little is known about their genomic organization, expression and regulation. To better understand how infection conditions may affect SM production in Metarhizium anisopliae, we have performed a deep survey and description of SM biosynthetic gene clusters (BGCs in M. anisopliae, analyzed RNA-seq data from fungi grown on cattle-tick cuticles, evaluated the differential expression of BGCs, and assessed conservation among the Metarhizium genus. Furthermore, our analysis extended to the construction of a phylogeny for the following three BGCs: a tropolone/citrinin-related compound (MaPKS1, a pseurotin-related compound (MaNRPS-PKS2, and a putative helvolic acid (MaTERP1. Results Among 73 BGCs identified in M. anisopliae, 20 % were up-regulated during initial tick cuticle infection and presumably possess virulence-related roles. These up-regulated BGCs include known clusters, such as destruxin, NG39x and ferricrocin, together with putative helvolic acid and, pseurotin and tropolone/citrinin-related compound clusters as well as uncharacterized clusters. Furthermore, several previously characterized and putative BGCs were silent or down-regulated in initial infection conditions, indicating minor participation over the course of infection. Interestingly, several up

  1. Application of an integrated LC-UV-MS-NMR platform to the identification of secondary metabolites from cell cultures: benzophenanthridine alkaloids from elicited Eschscholzia californica (california poppy) cell cultures().

    Science.gov (United States)

    Gathungu, Rose M; Oldham, John T; Bird, Susan S; Lee-Parsons, Carolyn W T; Vouros, Paul; Kautz, Roger

    2012-01-01

    Plant cell and tissue cultures are a scalable and controllable alternative to whole plants for obtaining natural products of medical relevance. Cultures can be optimized for high yields of desired metabolites using rapid profiling assays such as HPLC. We describe an approach to establishing a rapid assay for profiling cell culture expression systems using a novel microscale LC-UV-MS-NMR platform, designed to acquire both MS and NMR each at their optimal sensitivity, by using nanosplitter MS from 4 mm analytical HPLC columns, and offline microdroplet NMR. The approach is demonstrated in the analysis of elicited Eschscholzia californica cell cultures induced with purified yeast extract to produce benzophenanthridine alkaloids. Preliminary HPLC-UV provides an overview of the changes in the production of alkaloids with time after elicitation. At the time point corresponding to the production of the most alkaloids, the integrated LC-MS-microcoil NMR platform is used for structural identification of extracted alkaloids. Eight benzophenanthridine alkaloids were identified at the sub-microgram level. This paper demonstrates the utility of the nanosplitter LC-MS/microdroplet NMR platform when establishing cell culture expression systems.

  2. VLT Instruments Pipeline System Overview

    Science.gov (United States)

    Jung, Y.; Ballester, P.; Banse, K.; Hummel, W.; Izzo, C.; McKay, D. J.; Kiesgen, M.; Lundin, L. K.; Modigliani, A.; Palsa, R. M.; Sabet, C.

    2004-07-01

    Since the beginning of the VLT operations in 1998, substantial effort has been put in the development of automatic data reduction tools for the VLT instruments. A VLT instrument pipeline is a complex system that has to be able to identify and classify each produced FITS file, optionally retrieve calibration files from a database, use an image processing software to reduce the data, compute and log quality control parameters, produce FITS images or tables with the correct headers, optionally display them in the control room and send them to the archive. Each instrument has its own dedicated pipeline, based on a common infrastructure and installed with the VLT Data Flow System (DFS). With the increase in the number and the complexity of supported instruments and in the rate of produced data, these pipelines are becoming vital for both the VLT operations and the users, and request more and more resources for development and maintenance. This paper describes the different pipeline tasks with some real examples. It also explains how the development process has been improved to both decrease its cost and increase the pipelines quality using the lessons learned from the first instruments pipelines development.

  3. Numerical Recovery of Gas Flows in Pipeline Systems

    Directory of Open Access Journals (Sweden)

    Vadim E. Seleznev

    2012-01-01

    Full Text Available Optimal control, prevention and investigation of accidents, and detection of discrepancies in estimated gas supply and distribution volumes are relevant problems of trunkline operation. Efficient dealing with these production tasks is based on the numerical recovery of spacetime distribution of nonisothermal transient flow parameters of transmitted gas mixtures based on full-scale measurements in a substantially limited number of localities spaced considerable distances apart along the gas pipelines. The paper describes a practical method of such recovery by defining and solving a special identification problem. Simulations of product flow parameters in extended branched pipelines, involving calculations of the target function and constraint function for the identification problem of interest, are done in the 1D statement. In conclusion, results of practical application of the method in the gas industry are briefly discussed.

  4. Eight hours of nocturnal 915 MHz radiofrequency identification (RFID) exposure reduces urinary levels of melatonin and its metabolite via pineal arylalkylamine N-acetyltransferase activity in male rats.

    Science.gov (United States)

    Kim, Hye Sun; Paik, Man-Jeong; Lee, Yu Hee; Lee, Yun-Sil; Choi, Hyung Do; Pack, Jeong-Ki; Kim, Nam; Ahn, Young Hwan

    2015-01-01

    We investigated the effects of whole-body exposure to the 915 MHz radiofrequency identification (RFID) on melatonin biosynthesis and the activity of rat pineal arylalkylamine N-acetyltransferase (AANAT). Rats were exposed to RFID (whole-body specific absorption rate, 4 W/kg) for 8 h/day, 5 days/week, for weeks during the nighttime. Total volume of urine excreted during a 24-h period was collected after RFID exposure. Urinary melatonin and 6-hydroxymelatonin sulfate (6-OHMS) was measured by gas chromatography-mass spectrometry (GC-MS) and enzyme-linked immunosorbent assay (ELISA), respectively. AANAT enzyme activity was measured using liquid biphasic dif-13 fusion assay. Protein levels and mRNA expression of AANAT was 14 measured by Western blot and reverse transcription polymerase 15 chain reaction (RT-PCR) analysis, respectively. Eight hours of nocturnal RFID exposure caused a significant reduction in both urinary melatonin (p = 0. 003) and 6-OHMS (p = 0. 026). Activity, protein levels, and mRNA expression of AANAT were suppressed by exposure to RFID (p RFID exposure can cause reductions in the levels of both urinary melatonin and 6-OHMS, possibly due to decreased melatonin biosynthesis via suppression of Aanat gene transcription in the rat pineal gland.

  5. Recovery of blended product pipeline slops

    Energy Technology Data Exchange (ETDEWEB)

    Sloley, A.W. [Process Consulting Services, Inc., Houston, TX (United States)

    1996-09-01

    Both product pipeline operation and terminal blending often generate slops consisting of mixed hydrocarbon streams. Typical slops dispositions include local burning of the fuel for heat or power generation or reshipment to a refinery in a crude stream. Both of these dispositions can incur significant economic penalties. An alternative is the use of a small local plant for the separation of the streams back into pipeline products. This is achievable as long as blend stocks rather then final products containing performance additives are being separated. Final products (gasoline, diesel) contain additives and blending components difficult to handle within the constraints of a small process unit. A proposed multi-product separation unit is presented. The case investigated shows the process configuration required for a unit to process a range of mixtures containing material from LPG to atmospheric gas oil. The material presented includes the plant flow scheme, identification of major equipment, and overall sizing of major equipment. The study results summarize the investment and operating costs of the unit compared to the values of the recoverable products.

  6. Novel R Pipeline for Analyzing Biolog Phenotypic Microarray Data

    OpenAIRE

    Vehkala, Minna; Shubin, Mikhail; Connor, Thomas Richard; Thomson, Nicholas R.; Corander, Jukka

    2015-01-01

    Data produced by Biolog Phenotype MicroArrays are longitudinal measurements of cells' respiration on distinct substrates. We introduce a three-step pipeline to analyze phenotypic microarray data with novel procedures for grouping, normalization and effect identification. Grouping and normalization are standard problems in the analysis of phenotype microarrays defined as categorizing bacterial responses into active and non-active, and removing systematic errors from the experimental data, resp...

  7. Synthetic cannabinoids: analysis and metabolites.

    Science.gov (United States)

    Elsohly, Mahmoud A; Gul, Waseem; Wanas, Amira S; Radwan, Mohamed M

    2014-02-27

    Cannabimimetics (commonly referred to as synthetic cannabinoids), a group of compounds encompassing a wide range of chemical structures, have been developed by scientists with the hope of achieving selectivity toward one or the other of the cannabinoid receptors CB1 and CB2. The goal was to have compounds that could possess high therapeutic activity without many side effects. However, underground laboratories have used the information generated by the scientific community to develop these compounds for illicit use as marijuana substitutes. This chapter reviews the different classes of these "synthetic cannabinoids" with particular emphasis on the methods used for their identification in the herbal products with which they are mixed and identification of their metabolites in biological specimens.

  8. 75 FR 5244 - Pipeline Safety: Integrity Management Program for Gas Distribution Pipelines; Correction

    Science.gov (United States)

    2010-02-02

    ... implement integrity management programs. In addition to a minor correction in terminology, this document...: Integrity Management Program for Gas Distribution Pipelines; Correction AGENCY: Pipeline and...

  9. Local scour at submarine pipelines

    Institute of Scientific and Technical Information of China (English)

    Yee-Meng Chiew

    2010-01-01

    The rapid development of offshore oil_fields has increased the number of submarine pipelines being constructed for the transport of crude oil to onshore refineries.Interactions between the pipeline and an erodible bed under the influence of current and waves often lead to local scouring around the structure.When this occurs, the pipeline may be suspended on the seabed resulting in the formation of a span.If the free span is long enough, the pipe may experience resonant flow-induced oscillations,leading to structural failure.This study examines the complex flow-structure-sediment interaction leading to the development of local scour holes around submarine pipelines.It reviews published literature in this area,which primarily is confined to the development of 2-dimensional scour holes.Despite the abundance of such research studies,pipeline-scour in the field essentially is 3-dimensional in nature.Hence, most of these studies have overlooked the importance of the transverse dimension of the scour hole,while emphasizing on its vertical dimension.This dearly is an issue that must be re-examined in light of the potential hazard and environmental disaster that one faces in the event of a pipeline failure.Recent studies have begun to recognize this shortcoming,and attempts have been made to overcome the deficiency.The study presents the state-of-the-art knowledge on local scour at submarine pipelines,both from a 2-dimensional as well as the 3-dimensional perspective.

  10. China Oil & Gas Pipeline Survey & Design Institute, Pipeline

    Institute of Scientific and Technical Information of China (English)

    Bureau of CNPC; Zhao Surong

    1995-01-01

    @@ China Oil/Gas Pipeline Bureau(P.B) is the only professional organization in China specialized in oil/gas pipelines design and construction since 1980s. It has ever cooperated with certain number of well known companies from Japan,USA, Germany, Canada, as well as Italy in the designs of many large oil/gas pipeline projects, during the course of which, personnel from P.B accumulated much experience in international project designs. During the execution of each particular project, they strictly followed the common-use international codes and standards with computers as the auxiliary design system combined with the self-developed software. All its clients showed their trust in this organization and gave it high praise for its outstanding survey, design and technical service.

  11. Emergency preparedness of OSBRA Pipeline

    Energy Technology Data Exchange (ETDEWEB)

    Magalhaes, Milton P.; Torres, Carlos A.R.; Almeida, Francisco J.C. [TRANSPETRO, Rio de Janeiro, RJ (Brazil)

    2009-07-01

    This paper presents the experience of PETROBRAS Transporte S. A. - TRANSPETRO in the preparation for emergencies in the OSBRA pipeline, showing specific aspects and solutions developed. The company has a standardized approach for the emergency management, based on risk analysis studies, risk management plan and contingency plans. To cover almost 1,000 km of pipeline, the Company avails of Emergency Response Centers and Environmental Defense Center, located at strategic points. In order to achieve preparation, fire fighting training and oil leakage elimination training are provided. Additionally, simulation exercises are performed, following a schedule worked out according to specific criteria and guidelines. As a conclusion, a picture is presented of the evolution of the preparation for emergencies in the OSBRA System which bears the enormous responsibility of transporting flammable products for almost 1,000 km of pipeline, crossing 40 municipalities, 3 states and the Federal District. (author)

  12. Metabolism of cyadox by the intestinal mucosa microsomes and gut flora of swine, and identification of metabolites by high-performance liquid chromatography combined with ion trap/time-of-flight mass spectrometry.

    Science.gov (United States)

    Xu, Ning; Huang, Lingli; Liu, Zhenli; Pan, Yuanhu; Wang, Xu; Tao, Yanfei; Chen, Dongmei; Wang, Yulian; Peng, Dapeng; Yuan, Zong hui

    2011-08-30

    Cyadox (CYX), 2-formylquinoxaline-1,4-dioxide cyanoacetylhydrazone, is an antimicrobial and growth-promoting feed additive for food-producing animals. To reveal biotransformation of CYX in swine intestine, CYX was incubated with swine intestinal microsomes and mucosa in the presence of an NADPH-generating system and swine ileal flora and colonic flora, respectively. The metabolites of CYX were identified using high-performance liquid chromatography combined with ion trap/time-of-flight mass spectrometry (LC/MS-ITTOF). Structural elucidation of the metabolites was precisely performed by comparing their changes in molecular mass, full scan MS/MS spectra and accurate mass measurements with those of the parent drug. Finally, seven metabolites were identified as follows: three reduced metabolites (cyadox 1-monoxide (Cy1), cyadox 4-monoxide (Cy2) and bisdesoxycyadox (Cy4)); hydroxylation metabolite (3-hydroxylcyadox 1-monoxide (Cy3)); hydrolysis metabolite of the amide bond (N-decyanoacetyl cyadox (Cy5)); a hydrogenation metabolite (11,12-dihydro-bisdesoxycyadox (Cy6)) and a side-chain cleavage metabolite (2-hydromethylquinoxaline (Cy7)). Only one metabolite (Cy1) was found in intestinal microsomes. Cy1, Cy2 and Cy4 were detected in intestinal mucosa, ileal and colonic flora. In addition, Cy3 and Cy5 were only obtained from ileal flora, and Cy6 and Cy7 alone were observed in colonic bacteria. The results indicated that N→O group reduction was the main metabolic pathway of CYX metabolism in swine ileal flora, intestinal microsomes and mucosa. New metabolic profiles of hydrogenation and cleavage on the side chain were found in colonic bacteria. Among the identified metabolites, two new metabolites (Cy6, Cy7) were detected for the first time. These studies will contribute to clarify comprehensively the metabolism of CYX in animals, and provide evidence to explain the pharmacology and toxicology effects of CYX in animals.

  13. Identification of some Bioactive Metabolites in a Fractionated Methanol Extract from Ipomoea aquatica (Aerial Parts) through TLC, HPLC, UPLC-ESI-QTOF-MS and LC-SPE-NMR Fingerprints Analyses.

    Science.gov (United States)

    Hefny Gad, Mahmoud; Tuenter, Emmy; El-Sawi, Nagwa; Younes, Sabry; El-Ghadban, El-Mewafy; Demeyer, Kristiaan; Pieters, Luc; Vander Heyden, Yvan; Mangelings, Debby

    2017-08-04

    The plant species Ipomoea aquatica contains various bioactive constituents, e.g. phenols and flavonoids, which have several medical uses. All previous studies were executed in Asia; however, no reports are available from Africa, and the secondary metabolites of this plant species from Africa are still unknown. The present study aims finding suitable conditions to identify the bioactive compounds from different fractions. Chromatographic fingerprint profiles of different fractions were developed using high-performance liquid chromatography (HPLC) and then these conditions were transferred to thin-layer chromatography (TLC). Subsequently, the chemical structure of some bioactive compounds was elucidated using ultra-performance liquid chromatography-quadrupole time of flight-tandem mass spectrometry (UPLC-QTOF-MS) and liquid chromatography-solid phase extraction-nuclear magnetic resonance (LC-SPE-NMR) spectroscopy. The HPLC fingerprints, developed on two coupled Chromolith RP-18e columns, using a gradient mobile phase (methanol/water/trifluoroacetic acid, 5:95:0.05, v/v/v), showed more peaks than the TLC profile. The TLC fingerprint allows the identification of the types of chemical constituents, e.g. flavonoids. Two flavonoids (nicotiflorin and ramnazin-3-O-rutinoside) and two phenolic compounds (dihydroxybenzoic acid pentoside and di-pentoside) were tentatively identified by QTOF-MS, while NMR confirmed the structure of rutin and nicotiflorin. The HPLC and TLC results showed that HPLC fingerprints give more and better separated peaks, but TLC helped in determining the class of the active compounds in some fractions. Bioactive constituents were identified as well using MS and NMR analyses. Two flavonoids and two phenolic compounds were tentatively identified in this species for the first time, to the best of our knowledge. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

  14. Method and system for pipeline communication

    Science.gov (United States)

    Richardson,; John, G [Idaho Falls, ID

    2008-01-29

    A pipeline communication system and method includes a pipeline having a surface extending along at least a portion of the length of the pipeline. A conductive bus is formed to and extends along a portion of the surface of the pipeline. The conductive bus includes a first conductive trace and a second conductive trace with the first and second conductive traces being adapted to conformally couple with a pipeline at the surface extending along at least a portion of the length of the pipeline. A transmitter for sending information along the conductive bus on the pipeline is coupled thereto and a receiver for receiving the information from the conductive bus on the pipeline is also couple to the conductive bus.

  15. 77 FR 19799 - Pipeline Safety: Pipeline Damage Prevention Programs

    Science.gov (United States)

    2012-04-02

    ..., excavation, tunneling, or construction activity to establish the location of underground facilities in the demolition, excavation, tunneling, or construction area; 2. Disregard location information or markings... construction activity; and 3. Fail to report excavation damage to a pipeline facility to the owner or operator...

  16. 75 FR 13342 - Pipeline Safety: Workshop on Distribution Pipeline Construction

    Science.gov (United States)

    2010-03-19

    ... practices in natural gas distribution pipeline construction management and quality control. This workshop... St. Louis at the Ballpark, 1 South Broadway, St. Louis, MO 63102. Hotel reservations under the ``U.S...-845-7354. A daily base rate of $110.00 is available. The meeting room will be posted at the hotel on...

  17. 78 FR 41496 - Pipeline Safety: Meetings of the Gas and Liquid Pipeline Advisory Committees

    Science.gov (United States)

    2013-07-10

    ... Pipeline and Hazardous Materials Safety Administration Pipeline Safety: Meetings of the Gas and Liquid... for natural gas pipelines and for hazardous liquid pipelines. Both committees were established under.... ACTION: Notice of advisory committee meeting. SUMMARY: This notice announces a public meeting of the...

  18. California Natural Gas Pipelines: A Brief Guide

    Energy Technology Data Exchange (ETDEWEB)

    Neuscamman, Stephanie [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Price, Don [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Pezzola, Genny [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Glascoe, Lee [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States)

    2013-01-22

    The purpose of this document is to familiarize the reader with the general configuration and operation of the natural gas pipelines in California and to discuss potential LLNL contributions that would support the Partnership for the 21st Century collaboration. First, pipeline infrastructure will be reviewed. Then, recent pipeline events will be examined. Selected current pipeline industry research will be summarized. Finally, industry acronyms are listed for reference.

  19. PCE-1 oil pipeline/point A24 inch : inspection alternatives for a non-piggable pipeline

    Energy Technology Data Exchange (ETDEWEB)

    Franzoi, A.R.; Bueno, S.I.O. [Petrobras, Rio de Janeiro (Brazil); Camerini, C.S. [Petrobras, Rio de Janeiro (Brazil); Silva, J.A.P. [Pipeway Engenharia Ltda., Rio de Janeiro (Brazil); Vinicius, C.L. [Pontifica Univ. Catolica, Rio de Janeiro (Brazil)

    2004-07-01

    This paper provided details of flexpigs designed to both clean and inspect a 24 inch pipeline in Brazil. Originally built to be piggable, the pipeline had several areas with internal diameter restrictions. Small electronic devices were attached to the pigs in order to survey thermal profiles, pressure profiles and to locate areas with wax depositions. Additional corrosion detection instrumentation was also added to the flexpig due to its success in locating geometric obstructions. A differential magnetic coil (DMC) consisted of 2 coils with a core containing 2 permanent neodymium-iron-boron magnets. The DMC magnets generated a magnetic flux proportional to the quantity of material at the extremities of its poles. Corrosion defects caused imbalances in magnetic flux, which caused signals generated by the sensors to be amplified. The DMC sensors were mounted along the perimeter of the pig, while 2 odometers were fixed on the pig's rear flange. Initial trials of the pig resulted in damage to approximately 30 per cent of the sensors. Later attempts resulted in the successful identification of areas of corrosion along an 800 meter section of the pipeline. The areas were then excavated. Field verifications showed that the pig correctly identified areas of corrosion. Both the length and width of corrosion areas in the images obtained from the flexpig were identical to images recorded by an automatic ultrasonic tool. It was concluded that the modified flexpig is ideal for the inspection of non piggable pipelines. 2 refs., 13 figs.

  20. Research on Pipeline Holdup Measurement Technology

    Institute of Scientific and Technical Information of China (English)

    LU; Wen-guang; XU; Zheng; CHENG; Yi-mei; SUI; Hong-zhi; YIN; Hong-he

    2012-01-01

    <正>Some of the nuclear material could be deposited in the pipeline system of the nuclear facilities in the operation process. That kind of nuclear materials in the pipeline are called holdup. The measurement of pipeline holdup is not only important for the nuclear material accounting and control of facilities, but also important for the safe operation of facilities.

  1. Weight-of-evidence environmental risk assessment of dumped chemical weapons after WWII along the Nord-Stream gas pipeline in the Bornholm Deep.

    Science.gov (United States)

    Sanderson, Hans; Fauser, Patrik; Thomsen, Marianne; Larsen, Jørn Bo

    2012-05-15

    In connection with installation of two natural gas pipelines through the Baltic Sea between Russia and Germany, there has been concern regarding potential re-suspension of historically dumped chemical warfare agents (CWA) in a nearby dump site and the potential environmental risks associated. 192 sediment and 11 porewater samples were analyzed for CWA residues, both parent and metabolites in 2008 and 2010 along the pipeline corridor next to the dump site. Macrozoobenthos and background variables were also collected and compared to the observed CWA levels and predicted potential risks. Detection frequencies and levels of intact CWA found were low, whereas CWA metabolites were more frequently found. Re-suspension of CWA residue-containing sediment from installation of the pipelines contributes marginally to the overall background CWA residue exposure and risk along the pipeline route. The multivariate weight-of-evidence analysis showed that physical and background parameters of the sediment were of higher importance for the biota than observed CWA levels.

  2. Detecting abnormalities in gas pipelines

    Energy Technology Data Exchange (ETDEWEB)

    Smati, A. (Institut National des Hydrocarbures et de la Chimie, Bournerdes (Azerbaijan))

    1994-12-01

    The results of the measurement of the principal operating parameters can contain precious information on the condition of gas pipelines. This article explains how statistical tests may be useful in detecting anomalies that can occur on lines and in compressor stations. (author). 6 refs., 3 tabs., 1 fig.

  3. The data processing pipeline for the Herschel SPIRE Fourier Transform Spectrometer

    CERN Document Server

    Fulton, T; Polehampton, E T; Valtchanov, I; Hopwood, R; Lu, N; Baluteau, J -P; Mainetti, G; Pearson, C; Papageorgiou, A; Guest, S; Zhang, L; Imhof, P; Swinyard, B M; Griffin, M J; Lim, T L

    2016-01-01

    We present the data processing pipeline to generate calibrated data products from the Spectral and Photometric Imaging Receiver (SPIRE) imaging Fourier Transform Spectrometer on the Herschel Space Observatory. The pipeline processes telemetry from SPIRE observations and produces calibrated spectra for all resolution modes. The spectrometer pipeline shares some elements with the SPIRE photometer pipeline, including the conversion of telemetry packets into data timelines and calculation of bolometer voltages. We present the following fundamental processing steps unique to the spectrometer: temporal and spatial interpolation of the scan mechanism and detector data to create interferograms; Fourier transformation; apodization; and creation of a data cube. We also describe the corrections for various instrumental effects including first- and second-level glitch identification and removal, correction of the effects due to emission from the Herschel telescope and from within the spectrometer instrument, interferogra...

  4. Technical challenges of heavy wall HFW pipe production for Bord Gais Eireann pipeline project

    Energy Technology Data Exchange (ETDEWEB)

    O' Dwyer, Paul [Transmission Design Manager, Cork, (Ireland); Boothbym, Peter [MACAW Engineering Ltd., Newcastle, (United Kingdom); Tazedakis, Athanasios [Corinth Pipeworks S.A, Viotia, (Greece)

    2010-07-01

    This paper deals with the pipeline recently constructed by Bord Gais Eireann near the city of Cork in The Irish Republic. The 47.5 km pipeline comprises over 30 km of 9.5 mm and 17 km of 19.1 mm wall thickness for an outside diameter of 610 mm. This paper presents the global engineering approach adopted for the project and describes more in detail the specificities of the project and the challenges faced during production. One of the difficulties encountered was to manufacture a high strength pipeline of 19.1 mm wall thickness for HFW produced pipeline. The chemical composition of the 19.1 mm coil strip had also required new developments to accommodate the demanding drop weight tear test toughness requirement. Several methods were applied to mitigate potential risks such as increase of initial production test frequency, close monitoring during pipe production, identification of potential construction issues and the weldability performance were also tested.

  5. Shipbuilding pipeline production quality improvement

    Directory of Open Access Journals (Sweden)

    T. Buksa

    2010-06-01

    Full Text Available Purpose: The pipeline production is one of major processes in shipbuilding industry. Quality improvement and risk assessment in this process can yield significant savings, both in terms of internal quality costs as well as in terms of customer satisfactions.Design/methodology/approach: Shipbuilding pipeline production quality improvement has been carried out by application of FMEA (Failure Mode and Effect Analysis method. For the successful implementation of FMEA method it is necessary to identify process failure modes or possibility of the appearance of non-compliance, as well as their possible causes. For qualitative analysis of key input variables of the process, in the paper is used Ishikawa diagram and p-chart.Findings: It is shown that proposed approach to risk assessment in shipbuilding pipeline production is applicable to real casa scenario. The analysis has identified the points in the process with the highest probability of occurrence of nonconformities, or the highest risk for error.Research limitations/implications: As the experimenting has been conducted in shipyard, within production process, research schedule must have been set in accordance with production pace. Also, due to character of production process the data collecting was adopted to the production plan in that particular moment.Practical implications: Dealing with causes of potential nonconformities in the process can significantly contribute to the reliability and robustness of the process. Corrective actions that have been taken based on results of analysis significantly contributed to the level of quality in the pipeline production process.Originality/value: The pepper is dealing with a well known method applied in different production environment that are mostly conservative in production approach. It was shown that successful application of proposed approach can yield benefits especially in improved quality of produced pipelines within shipbuilding industry.

  6. Optical Fiber Pipeline Security Forewarning System

    Institute of Scientific and Technical Information of China (English)

    Jiang Qishan; Ren Ruijun; Ren Peikui

    2010-01-01

    @@ With the rapid development of China's economy,such incidents occurring to oil & gas pipelines as industrial and agricultural production,natural disasters,oil stealing,etc.have been prevailing and brought negative influences to the normal operation of pipelines.On account of all such destructive activities,firstly the soil around the pipeline should be vibrated,and then the cable laid in the pipe trench could respond to the vibration.Using this technology,the Department of Science & Technology of CNPC has embarked on the research of relevant equipment to monitor pipeline activities along the pipeline since 2001.

  7. A spectral-geophysical approach for detecting pipeline leakage

    Science.gov (United States)

    van der Meijde, M.; van der Werff, H. M. A.; Jansma, P. F.; van der Meer, F. D.; Groothuis, G. J.

    2009-02-01

    Leakage of hydrocarbon has a large economic and environmental impact. Traditional methods for investigating leakage and resulting pollution, such as drilling, are destructive, time consuming and expensive. Remote sensing is an alternative that is non-destructive and has been been tested extensively for exploration of onshore hydrocarbon reservoirs and detection of hydrocarbons at the Earth's surface. In this research, a leaking pipeline is investigated through field reflectance spectrometry and the findings are validated with traditional drilling and geophysical measurements. The measurements show a significant increase of vegetation anomalies on the pipeline with respect to areas further away. The observed anomalies are positively related to hydrocarbon pollution through chemical analysis of drillings. Subsurface geophysical measurements show a large correlation with observed surface vegetation stress, enhancing the identification of hydrocarbon-related vegetation stress through spectroscopy.

  8. Identification of a new metabolite of GHB

    DEFF Research Database (Denmark)

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

    2013-01-01

    report of a GHB glucuronide detected in biological samples. Given that glucuronides generally have longer half-life values than their corresponding free drugs, GHB-GLUC should theoretically be a biomarker of GHB intoxication. It is also proposed that the hitherto unexplained reports of elevated GHB...... concentrations in some biological samples, which has caused the setting of a relatively high cutoff value (10 µg/mL), represent total GHB measurements (sum of free GHB and actively chemically hydrolyzed GHB-GLUC). To address these challenges, the present study must be followed by comprehensive pharmacokinetic...

  9. Oil pipeline valve automation for spill reduction

    Energy Technology Data Exchange (ETDEWEB)

    Mohitpour, Mo; Trefanenko, Bill [Enbridge Technology Inc, Calgary (Canada); Tolmasquim, Sueli Tiomno; Kossatz, Helmut [TRANSPETRO - PETROBRAS Transporte S.A., Rio de Janeiro, RJ (Brazil)

    2003-07-01

    Liquid pipeline codes generally stipulate placement of block valves along liquid transmission pipelines such as on each side of major river crossings where environmental hazards could cause or are foreseen to potentially cause serious consequences. Codes, however, do not stipulate any requirement for block valve spacing for low vapour pressure petroleum transportation, nor for remote pipeline valve operations to reduce spills. A review of pipeline codes for valve requirement and spill limitation in high consequence areas is thus presented along with a criteria for an acceptable spill volume that could be caused by pipeline leak/full rupture. A technique for deciding economically and technically effective pipeline block valve automation for remote operation to reduce oil spilled and control of hazards is also provided. In this review, industry practice is highlighted and application of the criteria for maximum permissible oil spill and the technique for deciding valve automation thus developed, as applied to ORSUB pipeline is presented. ORSUB is one of the three initially selected pipelines that have been studied. These pipelines represent about 14% of the total length of petroleum transmission lines operated by PETROBRAS Transporte S.A. (TRANSPETRO) in Brazil. Based on the implementation of valve motorization on these three pipeline, motorization of block valves for remote operation on the remaining pipelines is intended, depending on the success of these implementations, on historical records of failure and appropriate ranking. (author)

  10. Upstream pipelines : inspection, corrosion and integrity management

    Energy Technology Data Exchange (ETDEWEB)

    Paez, J.; Stephenson, M. [Talisman Energy Inc., Calgary, AB (Canada)] (comps.)

    2009-07-01

    Accurate inspection techniques are needed to ensure the integrity of pipelines. This working group discussed methods of reducing pipeline failures for a variety of pipes. A summary of recent pipeline performance statistics was presented, as well as details of third party damage and fiberglass pipe failures. A batch inhibitor joint industry project was described. The session demonstrated that integrity program need to be developed at the field-level as well as at the upper management level. Fiberglass pipeline failures are significant problem for pipeline operators. Corrosion monitoring, pigging and specific budgets are needed in order to ensure the successful management of pipeline integrity. New software developed to predict pipeline corrosion rates was discussed, and methods of determining mole fractions and flow regimes were presented. The sessions included updates from regulators and standards agencies as well as discussions of best practices, regulations, codes and standards related to pipeline integrity. The working group was divided into 4 sessions: (1) updates since 2007 with input from the Canadian Association of Petroleum Producers (CAPP) and the Upstream Pipeline Integrity Management Association (UPIMA); (2) integrity of non-metallic pipelines; (3) upstream pipeline integrity issues; and (4) hot topics. tabs., figs.

  11. The MIRI Medium Resolution Spectrometer calibration pipeline

    CERN Document Server

    Labiano, A; Bailey, J I; Beard, S; Dicken, D; García-Marín, M; Geers, V; Glasse, A; Glauser, A; Gordon, K; Justtanont, K; Klaassen, P; Lahuis, F; Law, D; Morrison, J; Müller, M; Rieke, G; Vandenbussche, B; Wright, G

    2016-01-01

    The Mid-Infrared Instrument (MIRI) Medium Resolution Spectrometer (MRS) is the only mid-IR Integral Field Spectrometer on board James Webb Space Telescope. The complexity of the MRS requires a very specialized pipeline, with some specific steps not present in other pipelines of JWST instruments, such as fringe corrections and wavelength offsets, with different algorithms for point source or extended source data. The MRS pipeline has also two different variants: the baseline pipeline, optimized for most foreseen science cases, and the optimal pipeline, where extra steps will be needed for specific science cases. This paper provides a comprehensive description of the MRS Calibration Pipeline from uncalibrated slope images to final scientific products, with brief descriptions of its algorithms, input and output data, and the accessory data and calibration data products necessary to run the pipeline.

  12. Milk metabolites and their genetic variability.

    Science.gov (United States)

    Wittenburg, D; Melzer, N; Willmitzer, L; Lisec, J; Kesting, U; Reinsch, N; Repsilber, D

    2013-04-01

    The composition of milk is crucial to evaluate milk performance and quality measures. Milk components partly contribute to breeding scores, and they can be assessed to judge metabolic and energy status of the cow as well as to serve as predictive markers for diseases. In addition to the milk composition measures (e.g., fat, protein, lactose) traditionally recorded during milk performance test via infrared spectroscopy, novel techniques, such as gas chromatography-mass spectrometry, allow for a further analysis of milk into its metabolic components. Gas chromatography-mass spectrometry is suitable for measuring several hundred metabolites with high throughput, and thus it is applicable to study sources of genetic and nongenetic variation of milk metabolites in dairy cows. Heritability and mode of inheritance of metabolite measurements were studied in a linear mixed model approach including expected (pedigree) and realized (genomic) relationship between animals. The genetic variability of 190 milk metabolite intensities was analyzed from 1,295 cows held on 18 farms in Mecklenburg-Western Pomerania, Germany. Besides extensive pedigree information, genotypic data comprising 37,180 single nucleotide polymorphism markers were available. Goodness of fit and significance of genetic variance components based on likelihood ratio tests were investigated with a full model, including marker- and pedigree-based genetic effects. Broad-sense heritability varied from zero to 0.699, with a median of 0.125. Significant additive genetic variance was observed for highly heritable metabolites, but dominance variance was not significantly present. As some metabolites are particularly favorable for human nutrition, for instance, future research should address the identification of locus-specific genetic effects and investigate metabolites as the molecular basis of traditional milk performance test traits.

  13. A review: trichloroethylene metabolites: potential cardiac teratogens.

    OpenAIRE

    Johnson, P. D.; Dawson, B V; Goldberg, S J

    1998-01-01

    This review is a a series of the authors' studies designed to test the hypothesis that administration of trichloroethylene (TCE), dichloroethylene (DCE), their metabolites, and related compounds are responsible for fetal cardiac teratogenesis when given to pregnant rats during organogenesis. Identification of teratogenic compounds will allow more accurate assessment of environmental contaminants and public health risks. Epidemiologic studies and previous teratogenic studies using chick embryo...

  14. Russia: the pipeline diplomacy; Russie: la diplomatie du pipeline

    Energy Technology Data Exchange (ETDEWEB)

    Bourdillon, Y

    2005-01-15

    First world producer of oil and gas, Russia wishes to use its mastery of energy distribution to recover its great power status. The oil and gas pipelines network is the basement used by Russia to build up its hegemony in Europe. The Russian oil and gas companies are also carrying out a long-term strategy of international expansion, in particular thanks to investments in the neighboring countries for the building of new infrastructures or the purchase of oil refineries. (J.S.)

  15. Lowering of pipeline in the Peloneas's Beach and mechanical protection of pipeline in main and secondary piers; Rebaixamento de dutos na Praia das Peloneas e protecao mecanica de dutos nos piers principal e secundario

    Energy Technology Data Exchange (ETDEWEB)

    Teixeira, Ana Paula da Silva M.; Basilio, Kenia Afonso [PLANAVE, Rio de Janeiro, RJ (Brazil)

    2003-07-01

    The growing concern of PETROBRAS with the environmental protection aspects is intimately related with the need of developing preventive works of protection to the pipelines of the company. A study was accomplished in the pipelines inside the Guanabara Bay, whose goals was divided in three parts: identification of the risk areas for the pipelines; determination of the minimum depth of burying of the pipelines so that the risk in appreciation is minimized; identification of the areas in that the burying or a complemental burying make herself necessary. The study went based on to theory of conservation of energy, being admitted the non preservative embarkation system, and in the theory of the elasticity. For such a commercial program of finite elements was used. With base in the limits foreseen in the study, two critical areas of the Guanabara Bay were considered, which already suffered intervention with lowering. (author)

  16. Enhanced metabolite generation

    Science.gov (United States)

    Chidambaram, Devicharan [Middle Island, NY

    2012-03-27

    The present invention relates to the enhanced production of metabolites by a process whereby a carbon source is oxidized with a fermentative microbe in a compartment having a portal. An electron acceptor is added to the compartment to assist the microbe in the removal of excess electrons. The electron acceptor accepts electrons from the microbe after oxidation of the carbon source. Other transfers of electrons can take place to enhance the production of the metabolite, such as acids, biofuels or brewed beverages.

  17. Functional Genomics of Novel Secondary Metabolites from Diverse Cyanobacteria Using Untargeted Metabolomics

    Directory of Open Access Journals (Sweden)

    Muriel Gugger

    2013-09-01

    Full Text Available Mass spectrometry-based metabolomics has become a powerful tool for the detection of metabolites in complex biological systems and for the identification of novel metabolites. We previously identified a number of unexpected metabolites in the cyanobacterium Synechococcus sp. PCC 7002, such as histidine betaine, its derivatives and several unusual oligosaccharides. To test for the presence of these compounds and to assess the diversity of small polar metabolites in other cyanobacteria, we profiled cell extracts of nine strains representing much of the morphological and evolutionary diversification of this phylum. Spectral features in raw metabolite profiles obtained by normal phase liquid chromatography coupled to mass spectrometry (MS were manually curated so that chemical formulae of metabolites could be assigned. For putative identification, retention times and MS/MS spectra were cross-referenced with those of standards or available sprectral library records. Overall, we detected 264 distinct metabolites. These included indeed different betaines, oligosaccharides as well as additional unidentified metabolites with chemical formulae not present in databases of metabolism. Some of these metabolites were detected only in a single strain, but some were present in more than one. Genomic interrogation of the strains revealed that generally, presence of a given metabolite corresponded well with the presence of its biosynthetic genes, if known. Our results show the potential of combining metabolite profiling and genomics for the identification of novel biosynthetic genes.

  18. Functional Genomics of Novel Secondary Metabolites from Diverse Cyanobacteria Using Untargeted Metabolomics

    Science.gov (United States)

    Baran, Richard; Ivanova, Natalia N.; Jose, Nick; Garcia-Pichel, Ferran; Kyrpides, Nikos C.; Gugger, Muriel; Northen, Trent R.

    2013-01-01

    Mass spectrometry-based metabolomics has become a powerful tool for the detection of metabolites in complex biological systems and for the identification of novel metabolites. We previously identified a number of unexpected metabolites in the cyanobacterium Synechococcus sp. PCC 7002, such as histidine betaine, its derivatives and several unusual oligosaccharides. To test for the presence of these compounds and to assess the diversity of small polar metabolites in other cyanobacteria, we profiled cell extracts of nine strains representing much of the morphological and evolutionary diversification of this phylum. Spectral features in raw metabolite profiles obtained by normal phase liquid chromatography coupled to mass spectrometry (MS) were manually curated so that chemical formulae of metabolites could be assigned. For putative identification, retention times and MS/MS spectra were cross-referenced with those of standards or available sprectral library records. Overall, we detected 264 distinct metabolites. These included indeed different betaines, oligosaccharides as well as additional unidentified metabolites with chemical formulae not present in databases of metabolism. Some of these metabolites were detected only in a single strain, but some were present in more than one. Genomic interrogation of the strains revealed that generally, presence of a given metabolite corresponded well with the presence of its biosynthetic genes, if known. Our results show the potential of combining metabolite profiling and genomics for the identification of novel biosynthetic genes. PMID:24084783

  19. Analytic prognostic for petrochemical pipelines

    CERN Document Server

    Jaoude, Abdo Abou; El-Tawil, Khaled; Noura, Hassan; Ouladsine, Mustapha

    2012-01-01

    Pipelines tubes are part of vital mechanical systems largely used in petrochemical industries. They serve to transport natural gases or liquids. They are cylindrical tubes and are submitted to the risks of corrosion due to high PH concentrations of the transported liquids in addition to fatigue cracks due to the alternation of pressure-depression of gas along the time, initiating therefore in the tubes body micro-cracks that can propagate abruptly to lead to failure. The development of the prognostic process for such systems increases largely their performance and their availability, as well decreases the global cost of their missions. Therefore, this paper deals with a new prognostic approach to improve the performance of these pipelines. Only the first mode of crack, that is, the opening mode, is considered.

  20. The life of hydrotransport pipelines

    Energy Technology Data Exchange (ETDEWEB)

    Turchaninov, S.P.

    1973-01-01

    This book summarizes information on the hydroabrasive wear of pressurized pipes transporting bulk solid materials, such as coal. An analysis is presented of the operation of pipelines, and measures are recommended for their effective use. Methods of laboratory and production studies of hydroabrasive wear of pipes are described. The regularities of hydroabrasive wear of pipes are systematized as functions of the hydraulic characteristics of transportation and other operational factors. Methods are studied for increasing the durability of pipelines, and recommendations are given for determination of their throughput capacity through their entire service life. The book is designed for engineering and technical workers, planning-design and scientific research organizations, and may also be useful to university students. (87 refs.)

  1. Multi-level access control in the data pipeline of the international supply chain system

    NARCIS (Netherlands)

    Pruksasri, P.; Berg, J. van den; Hofman, W.; Daskapan, S.

    2013-01-01

    The Seamless Integrated Data Pipeline system was proposed to the European Union in order to overcome the information quality shortcomings of the current international supply chain information exchange systems. Next to identification and authorization of stakeholders, secure access control needs to b

  2. Airborne laser scanning to detect pipeline area invasions

    Energy Technology Data Exchange (ETDEWEB)

    Falat, Denise R.; Sallem Filho, Silas [ESTEIO Engenharia e Aerolevantamentos S.A, Curitiba, PR (Brazil)

    2009-07-01

    The occupation of the surface on the pipeline right-of-ways needs constant detailing and updating. The speed of changes in the vegetation areas and the irregular growth of urbanization prove the need for quick answers on the identification of invasions and on the elaboration of technical reports showing spatially referenced elements. In this context, this technical paper seeks to identify changes on the surface, making use of data derived from airborne LASER (Light Amplification by Stimulated Emission of Radiance) sensor scanning performed in different periods in the same study right-of-way. This technique has been successfully used in a number of applications, however, in most of the cases the LASER data are combined with digital photogrammetric products. This paper aims at the identification of alterations on the surface of right-of-ways and pipelines, using data exclusively from LASER scanning, performed in distinct periods. From the data processing are generated the DSM's (Digital Surface Models). The automatic comparison between the DSM's allows the identification of changes occurred between the surveys. Based on the configuration of the altered areas, we then expect to distinguish the several types of changes occurred as: new buildings, the advance of vegetation over right-of-ways and objects. For the validation of this methodology, photographic images of the regions have been used, obtained through photogrammetry in the same period of the LASER scanning. (author)

  3. Fragmentation trees for the structural characterisation of metabolites

    Science.gov (United States)

    Kasper, Piotr T; Rojas-Chertó, Miguel; Mistrik, Robert; Reijmers, Theo; Hankemeier, Thomas; Vreeken, Rob J

    2012-01-01

    Metabolite identification plays a crucial role in the interpretation of metabolomics research results. Due to its sensitivity and widespread implementation, a favourite analytical method used in metabolomics is electrospray mass spectrometry. In this paper, we demonstrate our results in attempting to incorporate the potentials of multistage mass spectrometry into the metabolite identification routine. New software tools were developed and implemented which facilitate the analysis of multistage mass spectra and allow for efficient removal of spectral artefacts. The pre-processed fragmentation patterns are saved as fragmentation trees. Fragmentation trees are characteristic of molecular structure. We demonstrate the reproducibility and robustness of the acquisition of such trees on a model compound. The specificity of fragmentation trees allows for distinguishing structural isomers, as shown on a pair of isomeric prostaglandins. This approach to the analysis of the multistage mass spectral characterisation of compounds is an important step towards formulating a generic metabolite identification method. Copyright © 2012 John Wiley & Sons, Ltd. PMID:22956319

  4. STATUS AND PROSPECT OF OIL AND GAS PIPELINES IN CHINA

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    @@ With the exploration and development of natural gas and the increase of crude oil import, the industry of China's Oil and Gas Pipelines has witnessed rapid development. Especially the gas pipeline industry is entering a peak period of development. Thanks to the completion and operation of large-scale pipeline projects including West-East Gas Transportation Pipeline project,Shanxi-Beijing Gas Pipeline Ⅱ, Ji-Ning Pipeline,Huaiyang-Wuhan Pipeline, Guangdong LNG Pipeline,Western Pipeline and Pearl River Delta Oil Product Pipeline, many trans-regional gas and oil pipeline networks with initial scale have been gradually established and improved in China. Meanwhile, the metallurgy,manufacturing and construction level of pipelines has been greatly developed, achieving world top level. The next five years is still a peak period of development for China's gas and oil pipeline industry which will enjoy a broader prospect.

  5. Metabolite identification of seven active components of Huan-Nao-Yi-Cong-Fang in rat plasma using high-performance liquid chromatography combined with hybrid ion trap/time-of-flight mass spectrometry.

    Science.gov (United States)

    Wang, Minchao; Lu, Yanzhen; Liu, Jiangang; Li, Hao; Wei, Yun

    2016-02-01

    Huan-Nao-Yi-Cong-Fang (HNYCF) is a potential prescription in treating Alzheimer's disease. Seven constituents [ferulic acid (FA), 2,3,5,4'-tetrahydroxystilbene-2-O-β-d-glucoside (THSG), berberine hydrochloride (BHCl), emodin, ginsenoside Rg1 (Rg1), ginsenoside Re (Re) and ginsenoside Rb1 (Rb1)] have been used as quality chemical markers of HNYCF owing to their biological significance and high contents in crude plant materials. This study explored the metabolites of the seven bioactive components in rat plasma to give useful data for further study of the action mechanism of HNYCF. LC/MS-IT-TOF was used to simultaneously characterize the metabolites of the seven components. Using the combination of MetID Solution 1.0 software and accurate mass measurements, the metabolites of HNYCF were reliably characterized. Their structures were elucidated based on the accurate MS(2) spectra and comparisons of their changes in accurate molecular masses and fragment ions with those of parent compounds. A total of five parent active compounds (BHCl, emodin, Rg1, Rb1 and Re) and 10 metabolites were found from the rat plasma 2 h after oral administration of HNYCF dosage, of which two metabolites of emodin were observed for the first time. The proposed metabolic pathways of the bioactive components in the rat plasma are helpful for further studies on the pharmacokinetics and real active compound forms of this drug.

  6. FPGA Implementation of Wave Pipelining CORDIC Algorithms

    Institute of Scientific and Technical Information of China (English)

    CUI Wei

    2008-01-01

    The implementation of the coordinate rotational digital computer (CORDIC) algorithm with wave pipelining technique on field programmable gate array (FPGA) is described. All data in FPGA-based wave pipelining pass through a number of logic gates, in the same way that all data pass through the same number of registers in a conventional pipeline. Moreover, all paths are routed using identical routing resources. The manual placement, timing driven routing and timing analyzing techniques are applied to optimize the layout for achieving good path balance. Experimental results show that a 256-LUT logic depth circuit mapped on XC4VLX15-12 runs as high as 330MHz, which is a little lower than the speed of 336MHz based on the conventional 16-stage pipelining in the same chip. The latency of the wave pipelining circuit is 30.3ns, which is 36.4% shorter than the latency of 16-stage conventional pipelining circuit.

  7. 49 CFR 195.9 - Outer continental shelf pipelines.

    Science.gov (United States)

    2010-10-01

    ... 49 Transportation 3 2010-10-01 2010-10-01 false Outer continental shelf pipelines. 195.9 Section... HAZARDOUS LIQUIDS BY PIPELINE General § 195.9 Outer continental shelf pipelines. Operators of transportation pipelines on the Outer Continental Shelf must identify on all their respective pipelines the specific...

  8. Characterization of corrosive bacterial consortia isolated from petroleum-product-transporting pipelines.

    Science.gov (United States)

    Rajasekar, Aruliah; Anandkumar, Balakrishnan; Maruthamuthu, Sundaram; Ting, Yen-Peng; Rahman, Pattanathu K S M

    2010-01-01

    Microbiologically influenced corrosion is a problem commonly encountered in facilities in the oil and gas industries. The present study describes bacterial enumeration and identification in diesel and naphtha pipelines located in the northwest and southwest region in India, using traditional cultivation technique and 16S rDNA gene sequencing. Phylogenetic analysis of 16S rRNA sequences of the isolates was carried out, and the samples obtained from the diesel and naphtha-transporting pipelines showed the occurrence of 11 bacterial species namely Serratia marcescens ACE2, Bacillus subtilis AR12, Bacillus cereus ACE4, Pseudomonas aeruginosa AI1, Klebsiella oxytoca ACP, Pseudomonas stutzeri AP2, Bacillus litoralis AN1, Bacillus sp., Bacillus pumilus AR2, Bacillus carboniphilus AR3, and Bacillus megaterium AR4. Sulfate-reducing bacteria were not detected in samples from both pipelines. The dominant bacterial species identified in the petroleum pipeline samples were B. cereus and S. marcescens in the diesel and naphtha pipelines, respectively. Therefore, several types of bacteria may be involved in biocorrosion arising from natural biofilms that develop in industrial facilities. In addition, localized (pitting) corrosion of the pipeline steel in the presence of the consortia was observed by scanning electron microscopy analysis. The potential role of each species in biofilm formation and steel corrosion is discussed.

  9. Characterization of corrosive bacterial consortia isolated from petroleum-product-transporting pipelines

    Energy Technology Data Exchange (ETDEWEB)

    Rajasekar, Aruliah; Ting, Yen-Peng [National Univ. of Singapore (Singapore). Dept. of Chemical and Biomolecular Engineering; Anandkumar, Balakrishnan [Sourashtra Coll., Madurai (India). Dept. of Biotechnology; Maruthamuthu, Sundaram [Central Electrochemical Research Inst., Karaikudi (India). Biocorrosion Group; Rahman, Pattanathu K.S.M. [Teesside Univ., Tees Valley (United Kingdom). Chemical and Bioprocess Engineering Group

    2010-01-15

    Microbiologically influenced corrosion is a problem commonly encountered in facilities in the oil and gas industries. The present study describes bacterial enumeration and identification in diesel and naphtha pipelines located in the northwest and southwest region in India, using traditional cultivation technique and 16S rDNA gene sequencing. Phylogenetic analysis of 16S rRNA sequences of the isolates was carried out, and the samples obtained from the diesel and naphtha-transporting pipelines showed the occurrence of 11 bacterial species namely Serratia marcescens ACE2, Bacillus subtilis AR12, Bacillus cereus ACE4, Pseudomonas aeruginosa AI1, Klebsiella oxytoca ACP, Pseudomonas stutzeri AP2, Bacillus litoralis AN1, Bacillus sp., Bacillus pumilus AR2, Bacillus carboniphilus AR3, and Bacillus megaterium AR4. Sulfate-reducing bacteria were not detected in samples from both pipelines. The dominant bacterial species identified in the petroleum pipeline samples were B. cereus and S. marcescens in the diesel and naphtha pipelines, respectively. Therefore, several types of bacteria may be involved in biocorrosion arising from natural biofilms that develop in industrial facilities. In addition, localized (pitting) corrosion of the pipeline steel in the presence of the consortia was observed by scanning electron microscopy analysis. The potential role of each species in biofilm formation and steel corrosion is discussed. (orig.)

  10. The PREP pipeline: standardized preprocessing for large-scale EEG analysis.

    Science.gov (United States)

    Bigdely-Shamlo, Nima; Mullen, Tim; Kothe, Christian; Su, Kyung-Min; Robbins, Kay A

    2015-01-01

    The technology to collect brain imaging and physiological measures has become portable and ubiquitous, opening the possibility of large-scale analysis of real-world human imaging. By its nature, such data is large and complex, making automated processing essential. This paper shows how lack of attention to the very early stages of an EEG preprocessing pipeline can reduce the signal-to-noise ratio and introduce unwanted artifacts into the data, particularly for computations done in single precision. We demonstrate that ordinary average referencing improves the signal-to-noise ratio, but that noisy channels can contaminate the results. We also show that identification of noisy channels depends on the reference and examine the complex interaction of filtering, noisy channel identification, and referencing. We introduce a multi-stage robust referencing scheme to deal with the noisy channel-reference interaction. We propose a standardized early-stage EEG processing pipeline (PREP) and discuss the application of the pipeline to more than 600 EEG datasets. The pipeline includes an automatically generated report for each dataset processed. Users can download the PREP pipeline as a freely available MATLAB library from http://eegstudy.org/prepcode.

  11. Fungal metabolite screening: database of 474 mycotoxins and fungal metabolites for dereplication by standardised liquid chromatography-UV-mass spectrometry methodology

    DEFF Research Database (Denmark)

    Nielsen, Kristian Fog; Smedsgaard, Jørn

    2003-01-01

    A standardised LC-UV-MS micro-scale method for screening of fungal metabolites and mycotoxins in culture extracts is presented. The paper includes data for detection and dereplication of >400 fungal metabolites to facilitate detection and identification when standards are not available. The data...

  12. Tubular lining material for pipelines having bends

    Energy Technology Data Exchange (ETDEWEB)

    Moringa, A.; Sakaguchi, Y.; Hyodo, M.; Yagi, I.

    1987-03-24

    A tubular lining material for pipelines having bends or curved portions comprises a tubular textile jacket made of warps and wefts woven in a tubular form overlaid with a coating of a flexible synthetic resin. It is applicable onto the inner surface of a pipeline having bends or curved portions in such manner that the tubular lining material with a binder onto the inner surface thereof is inserted into the pipeline and allowed to advance within the pipeline, with or without the aid of a leading rope-like elongated element, while turning the tubular lining material inside out under fluid pressure. In this manner the tubular lining material is applied onto the inner surface of the pipeline with the binder being interposed between the pipeline and the tubular lining material. The lining material is characterized in that a part of all of the warps are comprised of an elastic yarn around which, over the full length thereof, a synthetic fiber yarn or yarns have been left-and/or right-handedly coiled. This tubular lining material is particularly suitable for lining a pipeline having an inner diameter of 25-200 mm and a plurality of bends, such as gas service pipelines or house pipelines, without occurrence of wrinkles in the lining material in a bend.

  13. Transmission pipeline calculations and simulations manual

    CERN Document Server

    Menon, E Shashi

    2014-01-01

    Transmission Pipeline Calculations and Simulations Manual is a valuable time- and money-saving tool to quickly pinpoint the essential formulae, equations, and calculations needed for transmission pipeline routing and construction decisions. The manual's three-part treatment starts with gas and petroleum data tables, followed by self-contained chapters concerning applications. Case studies at the end of each chapter provide practical experience for problem solving. Topics in this book include pressure and temperature profile of natural gas pipelines, how to size pipelines for specified f

  14. A quick guide to pipeline engineering

    CERN Document Server

    Alkazraji, D

    2008-01-01

    Pipeline engineering requires an understanding of a wide range of topics. Operators must take into account numerous pipeline codes and standards, calculation approaches, and reference materials in order to make accurate and informed decisions.A Quick Guide to Pipeline Engineering provides concise, easy-to-use, and accessible information on onshore and offshore pipeline engineering. Topics covered include: design; construction; testing; operation and maintenance; and decommissioning.Basic principles are discussed and clear guidance on regulations is provided, in a way that will

  15. Gas pipeline optimization using adaptive algorithms

    Energy Technology Data Exchange (ETDEWEB)

    Smati, A.; Zemmour, N. [INH, Boumerdes (Algeria)

    1996-12-31

    Transmission gas pipeline network consume significant amounts of energy. Then, minimizing the energy requirements is a challenging task. Due to the nonlinearity and poor knowledge of the system states, several results, based on the optimal control theory, are obtained only for simple configurations. In this paper an optimization scheme in the face of varying demand is carried out. It is based on the use of a dynamic simulation program as a plant model and the Pareto set technique to sell out useful experiments. Experiments are used for the identification of regression models based on an original class of functions. The nonlinear programming algorithm results. Its connection with regression models permits the definition off-line, and for a long time horizon, of the optimal discharge pressure trajectory for all the compressor stations. The use of adaptive algorithms, with high frequency, permits one to cancel the effect of unknown disturbances and errors in demand forecasts. In this way, an on-line optimization scheme using data of SCADA system is presented.

  16. Leadership Succession: Future-proofing Pipelines.

    Science.gov (United States)

    Taylor, Saul; Youngs, Howard

    2017-09-12

    The challenges in deaf education illustrate the requirement and importance of leadership in this specialized field. The significant and impending talent depletion unfolding as baby-boomers retire, positions leadership succession planning as a strategic issue. This mixed methods study is the first of its kind in New Zealand. The aim is to understand leadership demographics and assumptions to determine the need for strategic succession planning to identify and address leaky pipelines. The findings from 82% of the deaf education workforce through a questionnaire and interviews with seven senior leaders reveal that senior leaders do not appear aware of four key areas that dissuade and shrink the pool of potential leadership aspirants. The four areas are prioritizing family; safeguarding health; concerns about bureaucracy, paperwork, and workload; and, a reluctance to move away from teaching. Aspirant identification appears informal, as there is no formal succession plan in place, which suggests a leadership crisis is imminent in New Zealand deaf education provision. Recommendations are provided that may help address this situation in New Zealand and other first-world nations if sufficient leaders are in place to deal with the challenges facing deaf education today and in the future. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  17. 77 FR 16471 - Pipeline Safety: Implementation of the National Registry of Pipeline and Liquefied Natural Gas...

    Science.gov (United States)

    2012-03-21

    ...: Implementation of the National Registry of Pipeline and Liquefied Natural Gas Operators AGENCY: Pipeline and... registry of pipeline and liquefied natural gas operators. This notice provides updates to the information... and liquefied natural gas (LNG) operators. New operators use the national registry to obtain...

  18. A review: trichloroethylene metabolites: potential cardiac teratogens.

    Science.gov (United States)

    Johnson, P D; Dawson, B V; Goldberg, S J

    1998-08-01

    This review is a a series of the authors' studies designed to test the hypothesis that administration of trichloroethylene (TCE), dichloroethylene (DCE), their metabolites, and related compounds are responsible for fetal cardiac teratogenesis when given to pregnant rats during organogenesis. Identification of teratogenic compounds will allow more accurate assessment of environmental contaminants and public health risks. Epidemiologic studies and previous teratogenic studies using chick embryos and fetal rats have reported an increased number of congenital cardiac defects when exposed to TCE or DCE during fetal development. Metabolites of TCE and DCE studied in the drinking-water exposure study include trichloroacetic acid TCAA), monochloroacetic acid, trichloroethanol, carboxymethylcysteine, trichloroacetaldehyde, dichloroacetaldehyde, and dichlorovinyl cysteine. Varying doses of each were given in drinking water to pregnant rats during the period of fetal heart development. Rats receiving 2730 ppm TCAA in drinking water were the only metabolite group demonstrating a significant increase in the number of cardiac defects in fetuses on a per-litter basis (p = 0.0004 Wilcoxon test and p =0.0015 exact permutation test). Maternal and fetal variables showed no statistically significant differences between treated and untreated groups. When treated with TCAA the increased cardiac defects, as compared to controls, do not preclude the involvement of other metabolites as cardiac teratogens, but indicates TCAA as a specific cardiac teratogen. Further studies of drinking-water exposure and potential mechanisms of action on the developing heart are proceeding.

  19. The CARMA Data Reduction Pipeline

    Science.gov (United States)

    Friedel, D. N.

    2013-10-01

    The Combined Array for Millimeter-wave Astronomy (CARMA) data reduction pipeline (CADRE) has been developed to give investigators a first look at a fully reduced set of their data. It runs automatically on all data produced by the telescope as they arrive in the data archive. CADRE is written in Python and uses Python wrappers for MIRIAD subroutines for direct access to the data. It applies passband, gain and flux calibration to the data sets and produces a set of continuum and spectral line maps in both MIRIAD and FITS format. CADRE has been in production for a year and this poster will discuss the current capabilities and planned improvements.

  20. Addressing the workforce pipeline challenge

    Energy Technology Data Exchange (ETDEWEB)

    Leonard Bond; Kevin Kostelnik; Richard Holman

    2006-11-01

    A secure and affordable energy supply is essential for achieving U.S. national security, in continuing U.S. prosperity and in laying the foundations to enable future economic growth. To meet this goal the next generation energy workforce in the U.S., in particular those needed to support instrumentation, controls and advanced operations and maintenance, is a critical element. The workforce is aging and a new workforce pipeline, to support both current generation and new build has yet to be established. The paper reviews the challenges and some actions being taken to address this need.

  1. 77 FR 51848 - Pipeline Safety: Information Collection Activities

    Science.gov (United States)

    2012-08-27

    ... Pipeline and Hazardous Materials Safety Administration Pipeline Safety: Information Collection Activities...) Current expiration date; (4) Type of request; (5) Abstract of the information collection activity; (6... activity. PHMSA requests comments on the following information collections: Title: Pipeline Safety:...

  2. 75 FR 30099 - Pipeline Safety: Information Collection Activities

    Science.gov (United States)

    2010-05-28

    ... TRANSPORTATION Pipeline and Hazardous Materials Safety Administration Pipeline Safety: Information Collection Activities AGENCY: Pipeline and Hazardous Materials Safety Administration, DOT. ACTION: Notice. SUMMARY: In compliance with the Paperwork Reduction Act, PHMSA announces that the currently approved...

  3. Oil and Natural Gas Pipelines, North America, 2010, Platts

    Data.gov (United States)

    U.S. Environmental Protection Agency — The Oil and Natural Gas Pipeline geospatial data layer contains gathering, interstate, and intrastate natural gas pipelines, crude and product oil pipelines, and...

  4. 18 CFR 284.227 - Certain transportation by intrastate pipelines.

    Science.gov (United States)

    2010-04-01

    ... Interstate Pipelines on Behalf of Others and Services by Local Distribution Companies § 284.227 Certain... interstate pipeline or local distribution company served by an interstate pipeline. (e) Pregrant...

  5. Selective capture and rapid identification of Panax notoginseng metabolites in rat faeces by the integration of magnetic molecularly imprinted polymers and high-performance liquid chromatography coupled with orbitrap mass spectrometry.

    Science.gov (United States)

    Cai, Qizhi; Yang, Zaiyue; Chen, Ning; Zhou, Xuemin; Hong, Junli

    2016-07-15

    In the present work, an advanced pretreatment method magnetic molecular imprinted polymers-dispersive solid phase extraction (MMIPs-DSPE) combined with the high sensitivity LTQ-Orbitrap mass spectrometry was applied to the complicated metabolites analysis of Traditional Chinese Medicines (TCMs) in complex matrices. The ginsenoside Rb1 magnetic molecular imprinted polymers (Rb1-MMIPs) were successfully synthesized for specific recognition and selective enrichment of Panax notoginseng saponin metabolites in rat faeces. The polymers were prepared by using Fe3O4@SiO2 as the supporting material, APTES as the functional monomer and TEOS as the cross-linker. The Rb1-MMIPs showed quick separation (10.8 emu/g), large adsorption capacity (636μmol/g), high selectivity and fast binding kinetics (25min). Dispersion solid-phase extraction using Rb1-MMIPs (Rb1-MMIPs-DSPE) integrated with LTQ-Orbitrap MS was applied to fish out and identify saponin metabolites from rat faeces, and totally 58 related compounds were detected within 20min, including 26 PPD-group and 32 PPT-group notoginsenoside metabolites. Parallel tests showed that Rb1-MMIPs-DSPE obtained the lowest matrix effects of 0.98-14.84% and captured the largest number of structural analogues compared with traditional pretreatment methods organic solvent extraction (OSE) and solid phase extraction (SPE).

  6. Identification of a novel glucosylsulfate conjugate as a metabolite of 3,4-dihydro-2,2-dimethyl-2H-naphtho[1,2-b]pyran-5,6-dione (ARQ 501, beta-lapachone) in mammals.

    Science.gov (United States)

    Savage, Ronald E; Tyler, Andrew N; Miao, Xiu-Sheng; Chan, Thomas C K

    2008-04-01

    3,4-Dihydro-2,2-dimethyl-2H-naphtho[1,2-b]pyran-5,6-dione (ARQ 501) is a fully synthetic version of the natural product beta-lapachone, which has been isolated from the lapacho tree (Tabebuia impetiginosa or Tabebuia avellanedae) and has demonstrated promising anticancer activity. ARQ 501 formulated with hydroxypropyl-beta-cyclodextrin has successfully completed phase I clinical trials and is currently in several phase II human clinical trials for the treatment of pancreatic cancer, head and neck cancer, and leiomyosarcoma. The metabolites of ARQ 501 were investigated by low-resolution and high-resolution mass spectrometry in plasma from (nu/nu) mice, rats, and humans treated with the compound. The data for one of the metabolites identified are consistent with conjugation of ARQ 501 with a glucosylsulfate moiety (m/z 241; fragment ion). Although other glucosylsulfate conjugates have been identified as metabolites of pesticides in cotton plants and in crustaceans as phase II metabolites of pyrenes, none have been previously identified in mammals. Data reported here identify a novel metabolic pathway for humans.

  7. Identification of the Metabolic Enzyme Involved Morusin Metabolism and Characterization of Its Metabolites by Ultraperformance Liquid Chromatography Quadrupole Time-of-Flight Mass Spectrometry (UPLC/Q-TOF-MS/MS

    Directory of Open Access Journals (Sweden)

    Xianbao Shi

    2016-01-01

    Full Text Available Morusin, the important active component of a traditional Chinese medicine, Morus alba L., has been shown to exhibit many vital pharmacological activities. In this study, six recombinant CYP450 supersomes and liver microsomes were used to perform metabolic studies. Chemical inhibition studies and screening assays with recombinant human cytochrome P450s were also used to characterize the CYP450 isoforms involved in morusin metabolism. The morusin metabolites identified varied greatly among different species. Eight metabolites of morusin were detected in the liver microsomes from pigs (PLMs, rats (RLMs, and monkeys (MLMs by LC-MS/MS and six metabolites were detected in the liver microsomes from humans (HLMs, rabbits (RAMs, and dogs (DLMs. Four metabolites (M1, M2, M5, and M7 were found in all species and hydroxylation was the major metabolic transformation. CYP1A2, CYP2C9, CYP2D6, CYP2E1, CYP3A4, and CYP2C19 contributed differently to the metabolism of morusin. Compared to other CYP450 isoforms, CYP3A4 played the most significant role in the metabolism of morusin in human liver microsomes. These results are significant to better understand the metabolic behaviors of morusin among various species.

  8. IDENTIFICATION WITH LIQUID-CHROMATOGRAPHY IONSPRAY MASS-SPECTROMETRY OF THE METABOLITES OF THE ENANTIOMERS N-METHYL DEXTRORPHAN AND N-METHYL LEVORPHANOL AFTER RAT-LIVER PERFUSION

    NARCIS (Netherlands)

    LANTING, ABL; BRUINS, AP; DRENTH, BFH; DEJONGE, K; ENSING, K; DEZEEUW, RA; MEIJER, DKF

    1993-01-01

    To gather more information on stereochemical factors in the hepatic disposition of organic cations, mass spectrometry coupled to liquid chromatography was used to determine the identity of the metabolites excreted in bile after isolated rat liver perfusions with the quaternary ammonium derivatives o

  9. Model-Free Predictive Anti-Slug Control of a Well-Pipeline-Riser

    Directory of Open Access Journals (Sweden)

    Christer Dalen

    2016-01-01

    Full Text Available Simplified linearized discrete time dynamic state space models are developed for a 3-phase well-pipeline-riser and tested together with a high fidelity dynamic model built in K-Spice and LedaFlow. In addition the Meglio pipeline-riser model is used as an example process. These models are developed from a subspace algorithm, i.e. Deterministic and Stochastic system identification and Realization (DSR, and implemented in a Model Predictive Controller (MPC for stabilizing the slugging regime. The MPC, LQR and PI control strategies are tested.

  10. Isolation and identification of 1,23-dihydroxyl-24,25,26,27-tetranorvitamin D/sub 3/, a new metabolite of 1,25-dihydroxyvitamin D/sub 3/ produced in rat kidney

    Energy Technology Data Exchange (ETDEWEB)

    Reddy, G.S.; Tserng, K.Y.; Thomas, B.R.; Dayal, R.; Norman, A.W.

    1987-01-13

    A new metabolite of vitamin D/sub 3/ was produced in vitro by perfusing rat kidneys with 1,25-dihydroxyvitamin D/sub 3/ (4 x 10/sup -6/M). It was isolated and purified from the lipid extract of the kidney perfusate by high-performance liquid chromatography. By means of ultraviolet absorption spectrophotometry, mass spectrometry, chemical derivatization, and chemical synthesis, the new metabolite was identified as 1,23-dihydroxy-24,25,26,27-tetranorvitamin D/sub 3/. Along with the new metabolite, three other previously identified metabolites, namely, 1,24,25-trihydroxyvitamin D/sub 3/, 1,25-dihydroxy-24-oxovitamin D/sub 3/, and 1,23,25-trihydroxy-24-oxovitamin D/sub 3/, were also isolated. The new metabolite was also formed when 1,23,25-trihydroxy-24-oxovitamin D/sub 3/ was used as the substrate. Thus, the new metabolite fits into the following metabolic pathway: 1,25-dihydroxyvitamin D/sub 3/ ..-->.. 1,24 (R),25-trihydroxyvitamin D/sub 3/ ..-->.. 1,25-dihydroxy-24-oxovitamin D/sub 3/ ..-->.. 1,23,25-trihydroxy-24-oxovitamin D/sub 3/ ..-->.. 1,23-dihydroxy-24,25,26,27-tetranorvitamin D/sub 3/. Further, they used 1..cap alpha..,25-dihydroxy(1..beta..-/sup 3/H)vitamin D/sub 3/ in the kidney perfusion system and demonstrated 1,23-dihydroxy-24,25,26,27-tetranorvitamin D/sub 3/ as the major further metabolite of 1,25-dihydroxyvitamin D/sub 3/, circulating in the final perfusate when kidneys were perfused with 1,25-dihydroxyvitamin D/sub 3/. The biological activity of 1,23-dihydroxy-24,25,26,27-tetranorvitamin D/sub 3/ (C-23 alcohol) and its metabolic relationship to 1-hydroxy-23-carboxy-24,25,26,27-tetranorvitamin D/sub 3/ are unknown and are presently undergoing investigation.

  11. 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.

  12. Review of Oil and Gas Pipeline Construction in 2007

    Institute of Scientific and Technical Information of China (English)

    Qu Hong

    2008-01-01

    @@ China's pipeline industry has developed for 50 years till 2008. In the past 10 years, more than 50,000 kilometers of long-distance oil and gas pipelines have been constructed,of which gas pipelines reached about 30,000 kilometers,crude oil pipelines about 17,000 kilometers, and product oil pipelines about 7,000 kilometers. Oil and gas pipeline networks across regions have taken shape.

  13. NCBI prokaryotic genome annotation pipeline.

    Science.gov (United States)

    Tatusova, Tatiana; DiCuccio, Michael; Badretdin, Azat; Chetvernin, Vyacheslav; Nawrocki, Eric P; Zaslavsky, Leonid; Lomsadze, Alexandre; Pruitt, Kim D; Borodovsky, Mark; Ostell, James

    2016-08-19

    Recent technological advances have opened unprecedented opportunities for large-scale sequencing and analysis of populations of pathogenic species in disease outbreaks, as well as for large-scale diversity studies aimed at expanding our knowledge across the whole domain of prokaryotes. To meet the challenge of timely interpretation of structure, function and meaning of this vast genetic information, a comprehensive approach to automatic genome annotation is critically needed. In collaboration with Georgia Tech, NCBI has developed a new approach to genome annotation that combines alignment based methods with methods of predicting protein-coding and RNA genes and other functional elements directly from sequence. A new gene finding tool, GeneMarkS+, uses the combined evidence of protein and RNA placement by homology as an initial map of annotation to generate and modify ab initio gene predictions across the whole genome. Thus, the new NCBI's Prokaryotic Genome Annotation Pipeline (PGAP) relies more on sequence similarity when confident comparative data are available, while it relies more on statistical predictions in the absence of external evidence. The pipeline provides a framework for generation and analysis of annotation on the full breadth of prokaryotic taxonomy. For additional information on PGAP see https://www.ncbi.nlm.nih.gov/genome/annotation_prok/ and the NCBI Handbook, https://www.ncbi.nlm.nih.gov/books/NBK174280/.

  14. Pipelined Viterbi Decoder Using FPGA

    Directory of Open Access Journals (Sweden)

    Nayel Al-Zubi

    2013-02-01

    Full Text Available Convolutional encoding is used in almost all digital communication systems to get better gain in BER (Bit Error Rate, and all applications needs high throughput rate. The Viterbi algorithm is the solution in decoding process. The nonlinear and feedback nature of the Viterbi decoder makes its high speed implementation harder. One of promising approaches to get high throughput in the Viterbi decoder is to introduce a pipelining. This work applies a carry-save technique, which gets the advantage that the critical path in the ACS feedback becomes in one direction and get rid of carry ripple in the “Add” part of ACS unit. In this simulation and implementation show how this technique will improve the throughput of the Viterbi decoder. The design complexities for the bit-pipelined architecture are evaluated and demonstrated using Verilog HDL simulation. And a general algorithm in software that simulates a Viterbi Decoder was developed. Our research is concerned with implementation of the Viterbi Decoders for Field Programmable Gate Arrays (FPGA. Generally FPGA's are slower than custom integrated circuits but can be configured in the lab in few hours as compared to fabrication which takes few months. The design implemented using Verilog HDL and synthesized for Xilinx FPGA's.

  15. Electrical fingerprint of pipeline defects

    Energy Technology Data Exchange (ETDEWEB)

    Mica, Isabella [STMicroelectronics Srl, via C.Olivetti 2, 20041 Agrate Brianza (Italy)]. E-mail: isabella.mica@st.com; Polignano, Maria Luisa [STMicroelectronics Srl, via C.Olivetti 2, 20041 Agrate Brianza (Italy); Marco, Cinzia De [STMicroelectronics Srl, via C.Olivetti 2, 20041 Agrate Brianza (Italy)

    2004-12-15

    Pipeline defects are dislocations that connect the source region of the transistor with the drain region. They were widely reported to occur in CMOS, BiCMOS devices and recently in SOI technologies. They can reduce device yield either by affecting the devices functionality or by increasing the current consumption under stand-by conditions. In this work the electrical fingerprint of these dislocations is studied, its purpose is to enable us to identify these defects as the ones responsible for device failure. It is shown that the pipeline defects are responsible for a leakage current from source to drain in the transistors. This leakage has a resistive characteristic and it is lightly modulated by the body bias. It is not sensitive to temperature; vice versa the off-current of a good transistor exhibits the well-known exponential dependence on 1/T. The emission spectrum of these defects was studied and compared with the spectrum of a good transistor. The paper aims to show that the spectrum of a defective transistor is quite peculiar; it shows well defined peaks, whereas the spectrum of a good transistor under saturation conditions is characterized by a broad spectral light emission distribution. Finally the deep-level transient spectroscopy (DLTS) is tried on defective diodes.

  16. Offshore Pipeline Locations in the Gulf of Mexico, Geographic NAD27, MMS (2007) [pipelines_points_mms_2007

    Data.gov (United States)

    Louisiana Geographic Information Center — Offshore Minerals Management Pipeline Locations for the Gulf of Mexico (GOM). Contains the points of the pipeline in the GOM. All pipelines existing in the databases...

  17. Offshore Pipeline Locations in the Gulf of Mexico, Geographic NAD27, MMS (2007) [pipelines_vectors_mms_2007

    Data.gov (United States)

    Louisiana Geographic Information Center — Offshore Minerals Management Pipeline Locations for the Gulf of Mexico (GOM). Contains the lines of the pipeline in the GOM. All pipelines existing in the databases...

  18. PETROCHINA WEST EAST GAS PIPELINE & SALES COMPANY

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    @@ PetroChina West East Gas Pipeline & Sales Company, a regional company directly under PetroChina Company Limited (PetroChina), is responsible for the construction and operation of the West-East Gas Pipeline Project, and the gas marketing and sales of the natural gas market in China.

  19. Testing the School-to-Prison Pipeline

    Science.gov (United States)

    Owens, Emily G.

    2017-01-01

    The School-to-Prison Pipeline is a social phenomenon where students become formally involved with the criminal justice system as a result of school policies that use law enforcement, rather than discipline, to address behavioral problems. A potentially important part of the School-to-Prison Pipeline is the use of sworn School Resource Officers…

  20. China Pins Hopes on Pipeline with Russia

    Institute of Scientific and Technical Information of China (English)

    2004-01-01

    @@ China still has faith in the gigantic Sino-Russia oil pipeline, despite reports which said that Russia is inclined to build a competing pipeline in favor of Japan. CNPC, the company representing China to negotiate with Russia on the project, is reported to continue its preparation work to receive Russian crude.

  1. Maurer computers for pipelined instruction processing

    NARCIS (Netherlands)

    Bergstra, J.A.; Middelburg, C.A.

    2008-01-01

    We model micro-architectures with non-pipelined instruction processing and pipelined instruction processing using Maurer machines, basic thread algebra and program algebra. We show that stored programs are executed as intended with these micro-architectures. We believe that this work provides a new

  2. Pipeline Protection Has Its Own Law

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    @@ The Law of the People's Republic of China on the Protection of Oil and Natural Gas Pipelines (hereinafter called "the Law") will be implemented officially on October 1 this year.This is the first time that oil and natural gas pipelines were protected and managed on legal basis.

  3. Metabolite production by differnt Ulocladium species

    DEFF Research Database (Denmark)

    Andersen, Birgitte; Hollensted, Morten

    2008-01-01

    Ulocladium, which is phylogenetically related to Alternaria, contains species that are food spoilers and plant pathogens, but also species that have potential as enzyme producers and bio-control agents. Ulocladium spp. are often found on dead vegetation, in soil, air and dust, but also on food...... and feedstuffs and on water-damaged building materials. The aim was to study the morphological and chemical diversity within the genus Ulocladium. Cultures of 52 Ulocladium strains were identified morphologically, and then extracted and analyzed using automated Chemical Image Analysis. Production of individual...... metabolites was correlated to species identity and source of isolation (substratum). Chemical analyses corroborated the morphological identifications and showed the existence of several species species-specific metabolites, of which most were known Compounds. The production of curvularins was specific...

  4. Efficiency improvements in pipeline transportation systems

    Energy Technology Data Exchange (ETDEWEB)

    Banks, W. F.; Horton, J. F.

    1977-09-09

    This report identifies potential energy-conservative pipeline innovations that are most energy- and cost-effective and formulates recommendations for the R, D, and D programs needed to exploit those opportunities. From a candidate field of over twenty classes of efficiency improvements, eight systems are recommended for pursuit. Most of these possess two highly important attributes: large potential energy savings and broad applicability outside the pipeline industry. The R, D, and D program for each improvement and the recommended immediate next step are described. The eight technologies recommended for R, D, and D are gas-fired combined cycle compressor station; internally cooled internal combustion engine; methanol-coal slurry pipeline; methanol-coal slurry-fired and coal-fired engines; indirect-fired coal-burning combined-cycle pump station; fuel-cell pump station; drag-reducing additives in liquid pipelines; and internal coatings in pipelines.

  5. optimization for trenchless reconstruction of pipelines

    Directory of Open Access Journals (Sweden)

    Zhmakov Gennadiy Nikolaevich

    2015-01-01

    Full Text Available Today the technologies of trenchless reconstruction of pipelines are becoming and more widely used in Russia and abroad. One of the most perspective is methods is shock-free destruction of the old pipeline being replaced with the help of hydraulic installations with working mechanism representing a cutting unit with knife disks and a conic expander. A construction of a working mechanism, which allows making trenchless reconstruction of pipelines of different diameters, is optimized and patented and its developmental prototype is manufactured. The dependence of pipeline cutting force from knifes obtusion of the working mechanisms. The cutting force of old steel pipelines with obtuse knife increases proportional to the value of its obtusion. Two stands for endurance tests of the knifes in laboratory environment are offered and patented.

  6. Cartier Pipeline : tying it all together

    Energy Technology Data Exchange (ETDEWEB)

    Brochu, S. [Enbridge Consumers Gas, Calgary, AB (Canada); Gaz Metropolitain, Montreal, PQ (Canada)

    2001-07-01

    The Cartier Pipeline is a proposed stand-alone pipeline involving equal partnership between Alberta's Enbridge Consumers Gas and Quebec's Gaz Metropolitain to bring offshore Atlantic gas to markets in eastern Canada and the New England states. The inservice date for the proposed pipeline is November 2004. The $270 million dollar project will require 262 km of pipeline in Quebec with an annual transportation capacity of 67 Bcf initially with a cost effective expandability to 125 Bcf. Contracted commitments so far include 30 Bcf/year from Gaz Metropolitain and the same from Enbridge. Cartier offers attractive, base load, long term, complementary market diversification for Atlantic production. It also provides producers with a competitive channel to Ontario storage. In addition, the pipeline will contribute to lower tolls in Canada and the overall path to Dracut (Boston). Several graphs depicting expected costs of delivered gas supplies to Montreal were also included with this power point presentation. tabs., figs.

  7. Technical progress in pipeline design and construction

    Energy Technology Data Exchange (ETDEWEB)

    Hausken, K.B.

    1995-12-31

    This paper considers the technical progress in offshore pipeline construction with limitation to some general subjects covering pipeline design, installation and start-up. In future the use of limit state pipeline design philosophy, may be implemented as an alternative to the stress based design commonly used to day giving a potential for further optimisation of the pipeline design and consequently reduction of the initial investment. Comprehensive research and development efforts in Norway in the second half of the 1970`s, made it technically feasible to cross the deep water Norwegian Trench in the 1980`s. In addition, the development of several offshore pipeline systems until to day including gas distribution systems to the European continent, have brought Norway to the forefront of technical expertise

  8. Pipeline modeling and assessment in unstable slopes

    Energy Technology Data Exchange (ETDEWEB)

    Caceres, Carlos Nieves [Oleoducto Central S.A., Bogota, Cundinamarca (Colombia); Ordonez, Mauricio Pereira [SOLSIN S.A.S, Bogota, Cundinamarca (Colombia)

    2010-07-01

    The OCENSA pipeline system is vulnerable to geotechnical problems such as faults, landslides or creeping slopes, which are well-known in the Andes Mountains and tropical countries like Colombia. This paper proposes a methodology to evaluate the pipe behaviour during the soil displacements of slow landslides. Three different cases of analysis are examined, according to site characteristics. The process starts with a simplified analytical model and develops into 3D finite element numerical simulations applied to the on-site geometry of soil and pipe. Case 1 should be used when the unstable site is subject to landslides impacting significant lengths of pipeline, pipeline is straight, and landslide is simple from the geotechnical perspective. Case 2 should be used when pipeline is straight and landslide is complex (creeping slopes and non-conventional stabilization solutions). Case 3 should be used if the pipeline presents vertical or horizontal bends.

  9. 应用GC-MS技术分离鉴定木薯叶片代谢物的极性组分%Isolation and Identification of Polar Metabolites in Cassava Leaf Using GC-MS Method

    Institute of Scientific and Technical Information of China (English)

    何秀全; 谭德冠; 孙雪飘; 彭明; 张家明

    2012-01-01

    Polar metabolites were extracted from leaf tissues of two cassava varieties with methanol, and derivatized with MSTFA. 36 compounds were separated and identified by GC-MS. Compared with the databases, we discovered some of the primary metabolites, sugars and small amounts of secondary metabolites. 2-hydroxy-Cyclohexanecarbonitrile, L-rhamnose, 2-(hydroxymethyl)-6- methoxytetrahydropyran-3, 4, 5-triol and 3 kinds of unknown metabolites were detected in SC124 only. Methyl dihydrogen phosphate, malonic acid, palmitic acid, a-Lyxopyranose and 2 kinds of unknown metabolites were only found in SC5. Other compounds and the content were basically the same in both leaves. The results suggested that cassava metabolites could be isolated and identified initially by this way.%利用甲醇溶液提取2个木薯品种SC124和SC5叶片的极性代谢组分,再用MSTFA衍生化,通过GCMS技术进行分离鉴定.结果表明:分离到30多种代谢产物,与数据库比对鉴定出31种成分,包括糖类和少量的次生代谢物;多数产物为2个品种共有,而且含量基本一致;少数产物具有品种特异性,其中只在SC124中检测到的代谢物有2-hydroxy-Cyclohexanecarbonitrile、L-rhamnose、2- (hydroxymethyl) -6-methoxytetrahydropyran3,4,5-triol和3种未知代谢物,而只在SC5中检测到的有methyl dihydrogen phosphate、Malonic acid、palmitic acid、a-Lyxopyranose和2种未知代谢物.本研究结果说明GC-MS技术不仅可分离鉴定木薯的代谢产物,而且还可发现木薯品种间代谢组的差异,具有较高的灵敏度.

  10. Glucuronidation of deoxynivalenol (DON) by different animal species: identification of iso-DON glucuronides and iso-deepoxy-DON glucuronides as novel DON metabolites in pigs, rats, mice, and cows.

    Science.gov (United States)

    Schwartz-Zimmermann, Heidi E; Hametner, Christian; Nagl, Veronika; Fiby, Iris; Macheiner, Lukas; Winkler, Janine; Dänicke, Sven; Clark, Erica; Pestka, James J; Berthiller, Franz

    2017-06-21

    The Fusarium mycotoxin deoxynivalenol (DON) is a frequent contaminant of cereal-based food and feed. Mammals metabolize DON by conjugation to glucuronic acid (GlcAc), the extent and regioselectivity of which is species-dependent. So far, only DON-3-glucuronide (DON-3-GlcAc) and DON-15-GlcAc have been unequivocally identified as mammalian DON glucuronides, and DON-7-GlcAc has been proposed as further DON metabolite. In the present work, qualitative HPLC-MS/MS analysis of urine samples of animals treated with DON (rats: 2 mg/kg bw, single bolus, gavage; mice: 1 mg/kg bw, single i.p. injection; pigs: 74 µg/kg bw, single bolus, gavage; cows: 5.2 mg DON/kg dry mass, oral for 13 weeks) revealed additional DON and deepoxy-DON (DOM) glucuronides. To elucidate their structures, DON and DOM were incubated with human (HLM) and rat liver microsomes (RLM). Besides the expected DON/DOM-3- and 15-GlcAc, minor amounts of four DON- and four DOM glucuronides were formed. Isolation and enzymatic hydrolysis of four of these compounds yielded iso-DON and iso-DOM, the identities of which were eventually confirmed by NMR. Incubation of iso-DON and iso-DOM with RLM and HLM yielded two main glucuronides for each parent compound, which were isolated and identified as iso-DON/DOM-3-GlcAc and iso-DON/DOM-8-GlcAc by NMR. Iso-DON-3-GlcAc, most likely misidentified as DON-7-GlcAc in the literature, proved to be a major DON metabolite in rats and a minor metabolite in pigs. In addition, iso-DON-8-GlcAc turned out to be one of the major DON metabolites in mice. DOM-3-GlcAc was the dominant DON metabolite in urine of cows and an important DON metabolite in rat urine. Iso-DOM-3-GlcAc was detected in urine of DON-treated rats and cows. Finally, DON-8,15-hemiketal-8-glucuronide, a previously described by-product of DON-3-GlcAc production by RLM, was identified in urine of DON-exposed mice and rats. The discovery of several novel DON-derived glucuronides in animal urine requires adaptation of

  11. UPLC-Q-TOF-MS/MS鉴定马钱苷大鼠体内代谢产物%Identification of Loganin Metabolites in Rats by UPLC-Q-TOF-MS/MS

    Institute of Scientific and Technical Information of China (English)

    王玉峰; 靳茂礼; 李松; 赵韶华; 刘敏彦

    2014-01-01

    Objective To identify the metabolites of loganin in rat urine through using ultra high performance liquid chromatography combined with triple TOF mass spectrometry (UPLC-Q-TOF/MS/MS) after oral administration of loganin;To summarize the metabolic pathway of loganin. Methods Rats were given a gavage with loganin. The urine samples were prepared by use of solid phase extraction (SPE). The chromatographic separation was performed on an UPLC C18 column with gradient elution program of acetonitrile and 0.1% formic acid aqueous as mobile phase. Dynamic background subtraction (DBS) technology was employed to trigger information dependent acquisition (IDA) to obtain the characteristic fragment ions of metabolites. Results MetabolitePilot software including several data processing methods were employed to speculate the structures of liganin metabolites and three metabolites were identified. Then, the metabolic pathway of loganin in rats was summarized. Conclusion The analytical method was simple, credible and highly-sensible, which is useful for screening and identifying trace constituents in vivo.%目的:采用超高效液相色谱与串联四级杆飞行时间质谱仪联用技术(UPLC-Q-TOF-MS/MS)分析鉴定大鼠灌胃马钱苷后其在尿液中的代谢产物,阐明马钱苷代谢途径。方法大鼠灌胃给予马钱苷,收集给药前后的尿样,经固相萃取进行预处理,采用超高液相色谱 C18色谱柱,流动相为乙腈-1%甲酸水,梯度洗脱,采用动态背景扣除(DBS)触发信息关联采集(IDA)进行MS/MS数据采集。结果经MetabolitePilot代谢物分析软件处理后,根据MS/MS给出质谱碎片信息对代谢产物进行结构推测,共鉴定马钱苷代谢物3种,并归纳了马钱苷在大鼠体内的代谢过程。结论该方法简单可靠,灵敏度高,可用于体内微量成分的分析鉴定。

  12. 77 FR 17119 - Pipeline Safety: Cast Iron Pipe (Supplementary Advisory Bulletin)

    Science.gov (United States)

    2012-03-23

    ... Pipeline and Hazardous Materials Safety Administration Pipeline Safety: Cast Iron Pipe (Supplementary... operators of natural gas cast iron distribution pipelines and state pipeline safety representatives. Recent deadly explosions in Philadelphia and Allentown, Pennsylvania involving cast iron pipelines installed...

  13. Metabolomic and Metagenomic Analysis of Two Crude Oil Production Pipelines Experiencing Differential Rates of Corrosion

    Science.gov (United States)

    Bonifay, Vincent; Wawrik, Boris; Sunner, Jan; Snodgrass, Emily C.; Aydin, Egemen; Duncan, Kathleen E.; Callaghan, Amy V.; Oldham, Athenia; Liengen, Turid; Beech, Iwona

    2017-01-01

    Corrosion processes in two North Sea oil production pipelines were studied by analyzing pig envelope samples via metagenomic and metabolomic techniques. Both production systems have similar physico-chemical properties and injection waters are treated with nitrate, but one pipeline experiences severe corrosion and the other does not. Early and late pigging material was collected to gain insight into the potential causes for differential corrosion rates. Metabolites were extracted and analyzed via ultra-high performance liquid chromatography/high-resolution mass spectrometry with electrospray ionization (ESI) in both positive and negative ion modes. Metabolites were analyzed by comparison with standards indicative of aerobic and anaerobic hydrocarbon metabolism and by comparison to predicted masses for KEGG metabolites. Microbial community structure was analyzed via 16S rRNA gene qPCR, sequencing of 16S PCR products, and MySeq Illumina shotgun sequencing of community DNA. Metagenomic data were used to reconstruct the full length 16S rRNA genes and genomes of dominant microorganisms. Sequence data were also interrogated via KEGG annotation and for the presence of genes related to terminal electron accepting (TEA) processes as well as aerobic and anaerobic hydrocarbon degradation. Significant and distinct differences were observed when comparing the ‘high corrosion’ (HC) and the ‘low corrosion’ (LC) pipeline systems, especially with respect to the TEA utilization potential. The HC samples were dominated by sulfate-reducing bacteria (SRB) and archaea known for their ability to utilize simple carbon substrates, whereas LC samples were dominated by pseudomonads with the genetic potential for denitrification and aerobic hydrocarbon degradation. The frequency of aerobic hydrocarbon degradation genes was low in the HC system, and anaerobic hydrocarbon degradation genes were not detected in either pipeline. This is in contrast with metabolite analysis, which

  14. Assessment and management of SCC in a liquid pipeline: case study

    Energy Technology Data Exchange (ETDEWEB)

    Cazenave, Pablo; Tandon, Samarth; Gao, Ming; Krishnamurthy, Ravi [Blade Energy Partners, Houston, Texas (United States); Peverelli, Romina (PIMS of London, London (United Kingdom)); Moreno Ochoa, Carlos (Pemex Refinacion, Cd de Mexico, (Mexico)); Diaz Solis, Esau (Pemex Refinacion, Cd de Mexico, (Mexico))

    2010-07-01

    A 30-inch crude oil pipeline system was built between Nuevo Teapa to Venta de Carpjo from 1978 to 1980. It is owned by Pemex; its total length is 570 km, and it has strategic importance in Mexico's refining capability. In this oil pipeline, various degrees of external and internal corrosion have been found, and recent incidents occurred as a result of stress corrosion cracking (SCC). This paper presents an approach for managing high pH SCC in such a pipeline: it includes a comprehensive verification excavation plan, a strict in-ditch NDT investigation protocol, statistical models to determine the probability of detection and identification, sizing tolerance analyses, and an assessment methodology that is backed up by the material testing program. All the results provided by the application of the approach lead to the development of integrity management strategies. An integrity management plan is established and refined before the next inspection.

  15. 21 CFR 862.3250 - Cocaine and cocaine metabolite test system.

    Science.gov (United States)

    2010-04-01

    ... treatment of cocaine use or overdose. (b) Classification. Class II. ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Cocaine and cocaine metabolite test system. 862... Test Systems § 862.3250 Cocaine and cocaine metabolite test system. (a) Identification. A cocaine and...

  16. Purification and H-1 NMR spectroscopic characterization of phase II metabolites of tolfenamic acid

    DEFF Research Database (Denmark)

    Sidelmann, U. G.; Christiansen, E.; Krogh, L.;

    1997-01-01

    acid; the study shows the applicability of H-1 NMR for the identification of drug metabolites in biological fluids. In addition to NMR analysis, two metabolites were also identified by mass spectrometry (MS), The glucuronides of the following parent compounds, N-(2-methyl-3-chlorophenyl...

  17. 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.

  18. Secondary metabolites from polar fractions of Piper umbellatum.

    Science.gov (United States)

    Tabopda, Turibio Kuiate; Mitaine-Offer, Anne-Claire; Miyamoto, Tomofumi; Tanaka, Chiaki; Ngadjuic, Bonaventure Tchaleu; Lacaille-Dubois, Marie-Aleth

    2012-05-01

    Seven known secondary metabolites were isolated from the methanol extract of the branches of Piper umbellatum. The identification of these compounds was mainly achieved by 2D NMR spectroscopic techniques and FAB-MS. Among them, the known cepharadiones A and B can be considered aschemotaxonomic markers of the genus Piper.

  19. Structural elucidation of low abundant metabolites in complex sample matrices

    NARCIS (Netherlands)

    Hooft, van der J.J.J.; Vos, de R.C.H.; Ridder, L.O.; Vervoort, J.; Bino, R.J.

    2013-01-01

    Identification of metabolites is a major challenge in biological studies and relies in principle on mass spectrometry (MS) and nuclear magnetic resonance (NMR) methods. The increased sensitivity and stability of both NMR and MS systems have made dereplication of complex biological samples feasible.

  20. Oxidative metabolites of lycopene and their biological functions

    Science.gov (United States)

    To gain a better understanding of the beneficial biological activities of lycopene on cancer prevention, a greater knowledge of the metabolism of lycopene is needed. In particular, the identification of lycopene metabolites and oxidation products in vivo; the importance of tissue specific lycopene c...

  1. SNIT: SNP identification for strain typing

    Directory of Open Access Journals (Sweden)

    Reifman Jaques

    2011-09-01

    Full Text Available Abstract With ever-increasing numbers of microbial genomes being sequenced, efficient tools are needed to perform strain-level identification of any newly sequenced genome. Here, we present the SNP identification for strain typing (SNIT pipeline, a fast and accurate software system that compares a newly sequenced bacterial genome with other genomes of the same species to identify single nucleotide polymorphisms (SNPs and small insertions/deletions (indels. Based on this information, the pipeline analyzes the polymorphic loci present in all input genomes to identify the genome that has the fewest differences with the newly sequenced genome. Similarly, for each of the other genomes, SNIT identifies the input genome with the fewest differences. Results from five bacterial species show that the SNIT pipeline identifies the correct closest neighbor with 75% to 100% accuracy. The SNIT pipeline is available for download at http://www.bhsai.org/snit.html

  2. In vitro identification of metabolites of verapamil in rat liver microsomes%维拉帕米在大鼠肝微粒体中代谢产物的体外鉴定

    Institute of Scientific and Technical Information of China (English)

    孙璐; 张淑秋; 钟大放

    2004-01-01

    AIM: To investigate the metabolism of verapamil at low concentrations in rat liver microsomes. METHODS: Liver microsomes of Wistar rats were prepared using ultracentrifuge method. The in vitro metabolism of verapamil was studied with the rat liver microsomal incubation at concentration of 1.0 μmol/L and 5.0 μmol/L. The metabolites were separated and assayed by liquid chromatography-ion trap mass spectrometry (LC/MSn), and further identified by comparison of their mass spectra and chromatographic behaviors with reference substances. RESULTS: Eight metabolites, including two novel metabolites (M4 and M8), were found in rat liver microsomal incubates. They were identified as O-demethyl-verapamil isomers (M1 - M4), N-dealkylated derivatives of verapamil (M5-M7), and N, O-didemethyl-verapamil (M8). CONCLUSION: O-Demethylation and N-dealkylation were the main metabolic pathways of verapamil at low concentrations in rat liver microsomes, and the relative proportion of them in verapamil metabolism changed with different substrate concentrations.

  3. Identification of the metabolites of biologically active xanthones isolated from Halenia elliptica D.Don by high performance liquid chromatography coupled to ion trap time-of-flight mass spectrometry

    Institute of Scientific and Technical Information of China (English)

    Ru Feng; Jian Gong Shi; Xiao Wei Liu; Chun Tao Che; John H.K. Yeung; Yan Wang

    2011-01-01

    Metabolism study has been carried out on l-hydroxy-2,3,5-trimethoxyxanthone (HM-1) and l-hydroxy-2,3,4,7-tetramethoxyxanthone (HM-2), which are two biologically active ingredients isolated from the Tibetan herb, Halenia elliptica D. Don., in rat liver microsomes in vitro. A method of high performance liquid chromatography coupled to ion trap time-of-flight mass spectrometry (LCMSn-ESI-IT-TOF) was applied to analyze metabolites of HM-1 and HM-2 on line, and five metabolites were identified containing l,5-dihydroxy-2,3-dimethoxyxanthone (HM-5), l,7-dihydroxy-2,3,4-trimethoxyxanthone (HM-9), 1,4, 7-trihydroxy-2,3-dimethoxyxanthone (HM-10), l,4-dihydroxy-2,3,7-trimethoxyxanthone (HM-11) and l,2-dihydroxy-3,4,7-trimethoxyxanthone (HM-12). Among these metabolites, HM-9, HM-11, and HM-12 were isomers mutually. The results indicated that HM-1 and HM-2 occurred Phase I metabolic reaction of demethylation in rat microsomes in vitro.

  4. Plasma profiling of intact isoflavone metabolites by high-performance liquid chromatography and mass spectrometric identification of flavone glycosides daidzin and genistin in human plasma after administration of kinako.

    Science.gov (United States)

    Hosoda, Kaori; Furuta, Takashi; Yokokawa, Akitomo; Ogura, Kenichiro; Hiratsuka, Akira; Ishii, Kazuo

    2008-08-01

    The roles of isoflavones in the prevention of several hormone-dependent cancers and osteoporosis are of great interest. Despite many pharmacokinetics studies of the isoflavones, the actual types of conjugates circulating in the body and the position(s) of conjugation sites on the flavone skeleton are still uncertain because, in general, conjugated compounds in biological fluids have been evaluated by measuring the free aglycones obtained after selective enzymatic hydrolysis. Using an high-performance (HPLC)-UV-diode-array detector (DAD) method combined with solid-phase extraction, we have obtained HPLC profiles of isoflavone glycosides [daidzin (Din) and genistin (Gin)] and of intact isoflavone metabolites in human plasma: daidzein, genistein, daizein-7-glucuronide, daidzein-4'-glucuronide, genistein-7-glucuronide, genistein-4'-glucuronide, daidzein-7-sulfate, daidzein-4'-sulfate, genistein-7-sulfate, and genistein-4'-sulfate. We investigated the plasma profile of intact isoflavone metabolites in plasma obtained 1 to-7 h after orally administration of 50 g of kinako (baked soybean powder) to two healthy volunteers. The results of DAD analysis indicated that the main isoflavone metabolite peaks were identified on the HPLC chromatogram. Furthermore, the intact glycosides Din and Gin were detected in 1-h plasma samples by their positive electrospray ionization mass spectra, demonstrating that the glycosides Din and Gin can be absorbed from the gut.

  5. Biotransformation of Total Saponins in Siraitia Fructus by Human Intestinal Microbiota of Normal and Type 2 Diabetic Patients: Comprehensive Metabolite Identification and Metabolic Profile Elucidation Using LC-Q-TOF/MS.

    Science.gov (United States)

    Zhou, Guisheng; Peng, Ying; Zhao, Lijuan; Wang, Mengyue; Li, Xiaobo

    2017-03-01

    Siraitia fructus, known as Luo-Han-Guo (LHG) in Chinese, shows good antidiabetic activity. Gut microbiota have emerged as parameter of the pathophysiology of type 2 diabetes (t2D) mellitus. In this study, in vitro biotransformation of LHG extract by t2D and normal human intestinal microbiota was analyzed using ultraperformance liquid chromatography with time-of-flight mass spectrometry. A total of 19 and 12 metabolites were characterized in t2D and normal human intestinal microbiota, respectively. These metabolites were formed by a series of metabolic reactions including deglycosylation, oxidation, isomerization, and/or deoxidation. The metabolite classes of LHG extract in normal and t2D human intestinal microbiota were nearly the same, but oxidation and isomerization reactions were usually present in t2D human intestinal bacteria. This might be due to metabolic activation by pathological human intestinal bacteria. Our study indicates that there are differences in the biotransformation of LHG extract in normal and t2D human intestinal bacteria.

  6. Remote monitoring of pipeline operations

    Energy Technology Data Exchange (ETDEWEB)

    Bost, R.C. [ERM-Southwest, Inc., Houston, TX (United States); White, D. [Glenrose Systems, Austin, TX (United States)

    1995-12-31

    The demands for monitoring of pipeline operations have recently increased greatly due to new regulatory requirements. Most companies rely upon conventional System Control and Data Acquisition (SCADA) system architecture to meet their needs. Current systems are often plagued by limited data conversion and processing capacity at the workstations. A state-of-the-art Data Acquisition Node (DAN) that relieves the workstation of much of its workload is described in this paper. Use of this DAN may eliminate the need for installing completely new systems. It facilitates marrying foreign devices to existing operation monitoring systems to satisfy new regulatory requirements. The DAN allows a system to utilize commercial communications satellites or other communication networks and real-time, object oriented programming and different devices and data requirements without the necessity of custom software development.

  7. Current pipelines for neglected diseases.

    Directory of Open Access Journals (Sweden)

    Paolo di Procolo

    2014-09-01

    Full Text Available This paper scrutinises pipelines for Neglected Diseases (NDs, through freely accessible and at-least-weekly updated trials databases. It updates to 2012 data provided by recent publications, and integrates these analyses with information on location of trials coordinators and patients recruitment status. Additionally, it provides (i disease-specific information to better understand the rational of investments in NDs, (ii yearly data, to understand the investment trends. The search identified 650 clinical studies. Leishmaniasis, Arbovirus infection, and Dengue are the top three diseases by number of clinical studies. Disease diffusion risk seems to be the most important driver of the clinical trials target choice, whereas the role played by disease prevalence and unmet need is controversial. Number of trials is stable between 2005 and 2010, with an increase in the last two years. Patient recruitment was completed for most studies (57.6%, and Phases II and III account for 35% and 28% of trials, respectively. The primary purpose of clinical investigations is prevention (49.3%, especially for infectious diseases with mosquitoes and sand flies as the vector, and treatment (43.2%, which is the primary target for parasitic diseases Research centres and public organisations are the most important clinical studies sponsors (58.9%, followed by the pharmaceutical industry (24.1%, foundations and non-governmental organisations (9.3%. Many coordinator centres are located in less affluent countries (43.7%, whereas OECD countries and BRICS account for 34.7% and 17.5% of trials, respectively. Information was partially missing for some parameters. Notwithstanding, and despite its descriptive nature, this research has enhanced the evidence of the literature on pipelines for NDs. Future contributions may further investigate whether trials metrics are consistent with the characteristics of the interested countries and the explicative variables of trials location

  8. Current pipelines for neglected diseases.

    Science.gov (United States)

    di Procolo, Paolo; Jommi, Claudio

    2014-09-01

    This paper scrutinises pipelines for Neglected Diseases (NDs), through freely accessible and at-least-weekly updated trials databases. It updates to 2012 data provided by recent publications, and integrates these analyses with information on location of trials coordinators and patients recruitment status. Additionally, it provides (i) disease-specific information to better understand the rational of investments in NDs, (ii) yearly data, to understand the investment trends. The search identified 650 clinical studies. Leishmaniasis, Arbovirus infection, and Dengue are the top three diseases by number of clinical studies. Disease diffusion risk seems to be the most important driver of the clinical trials target choice, whereas the role played by disease prevalence and unmet need is controversial. Number of trials is stable between 2005 and 2010, with an increase in the last two years. Patient recruitment was completed for most studies (57.6%), and Phases II and III account for 35% and 28% of trials, respectively. The primary purpose of clinical investigations is prevention (49.3%), especially for infectious diseases with mosquitoes and sand flies as the vector, and treatment (43.2%), which is the primary target for parasitic diseases Research centres and public organisations are the most important clinical studies sponsors (58.9%), followed by the pharmaceutical industry (24.1%), foundations and non-governmental organisations (9.3%). Many coordinator centres are located in less affluent countries (43.7%), whereas OECD countries and BRICS account for 34.7% and 17.5% of trials, respectively. Information was partially missing for some parameters. Notwithstanding, and despite its descriptive nature, this research has enhanced the evidence of the literature on pipelines for NDs. Future contributions may further investigate whether trials metrics are consistent with the characteristics of the interested countries and the explicative variables of trials location, target

  9. The LOFAR Known Pulsar Data Pipeline

    CERN Document Server

    Alexov, A; Mol, J D; Stappers, B; van Leeuwen, J

    2010-01-01

    Transient radio phenomena and pulsars are one of six LOFAR Key Science Projects (KSPs). As part of the Transients KSP, the Pulsar Working Group (PWG) has been developing the LOFAR Pulsar Data Pipelines to both study known pulsars as well as search for new ones. The pipelines are being developed for the Blue Gene/P (BG/P) supercomputer and a large Linux cluster in order to utilize enormous amounts of computational capabilities (50Tflops) to process data streams of up to 23TB/hour. The LOFAR pipeline output will be using the Hierarchical Data Format 5 (HDF5) to efficiently store large amounts of numerical data, and to manage complex data encompassing a variety of data types, across distributed storage and processing architectures. We present the LOFAR Known Pulsar Data Pipeline overview, the pulsar beam-formed data format, the status of the pipeline processing as well as our future plans for developing the LOFAR Pulsar Search Pipeline. These LOFAR pipelines and software tools are being developed as the next gen...

  10. OPUS: the FUSE science data pipeline

    Science.gov (United States)

    Rose, James F.; Heller-Boyer, C.; Rose, M. A.; Swam, M.; Miller, W.; Kriss, G. A.; Oegerle, William R.

    1998-07-01

    This paper describes how the OPUS pipeline, currently used for processing science data from the Hubble Space Telescope (HST), was used as the backbone for developing the science data pipeline for a much smaller mission. The far ultraviolet spectroscopic explorer (FUSE) project selected OPUS for its data processing pipeline platform and selected the OPUS team at the STScI to write the FUSE pipeline applications. A total of 105 new modules were developed for the FUSE pipeline. The foundation of over 250 modules in the OPUS libraries allowed development to proceed quickly and with considerable confidence that the underlying functionality is reliable and robust. Each task represented roughly 90 percent reuse, and the project as a whole shows over 70 percent reuse of the existing OPUS system. Taking an existing system that is operational, and will be maintained for many years to come, was a key decision for the FUSE mission. Adding the extensive experience of the OPUS team to the task resulted in the development of a complete telemetry pipeline system within a matter of months. Reusable software has been the siren song of software engineering and object- oriented design for a decade or more. The development of inexpensive software systems by adapting existing code to new applications is as attractive as it has been elusive. The OPUS telemetry pipeline for the FUSE mission has proven to be a significant exception to that trend.

  11. Crossing Active Faults on the Sakhalin II Onshore Pipeline Route: Analysis Methodology and Basic Design

    Science.gov (United States)

    Vitali, Luigino; Mattiozzi, Pierpaolo

    2008-07-01

    Twin oil (20 & 24 inch) and gas (20 & 48 inch) pipeline systems stretching 800 km are being constructed to connect offshore hydrocarbon deposits from the Sakhalin II concession in the North to an LNG plant and oil export terminal in the South of Sakhalin island. The onshore pipeline route follows a regional fault zone and crosses individual active faults at 19 locations. Sakhalin Energy, Design and Construction companies took significant care to ensure the integrity of the pipelines, should large seismic induced ground movements occur during the Operational life of the facilities. Complex investigations including the identification of the active faults, their precise location, their particular displacement values and assessment of the fault kinematics were carried out to provide input data for unique design solutions. Lateral and reverse offset displacements of 5.5 and 4.5 m respectively were determined as the single-event values for the design level earthquake (DLE)—the 1000-year return period event. Within the constraints of a pipeline route largely fixed, the underground pipeline fault crossing design was developed to define the optimum routing which would minimize stresses and strain using linepipe materials which had been ordered prior to the completion of detailed design, and to specify requirements for pipe trenching shape, materials, drainage system, etc. This Paper describes the steps followed to formulate the concept of the special trenches and the analytical characteristics of the Model.

  12. Basic Block of Pipelined ADC Design Requirements

    Directory of Open Access Journals (Sweden)

    V. Kledrowetz

    2011-04-01

    Full Text Available The paper describes design requirements of a basic stage (called MDAC - Multiplying Digital-to- Analog Converter of a pipelined ADC. There exist error sources such as finite DC gain of opamp, capacitor mismatch, thermal noise, etc., arising when the switched capacitor (SC technique and CMOS technology are used. These non-idealities are explained and their influences on overall parameters of a pipelined ADC are studied. The pipelined ADC including non-idealities was modeled in MATLAB - Simulink simulation environment.

  13. Suriname installing first crude-oil pipeline

    Energy Technology Data Exchange (ETDEWEB)

    McAllister, E.W. (E.W. McAllister Engineering Services, Houston, TX (US))

    1992-04-27

    This paper reports that the first cross country crude-oil pipeline in the south American country of Suriname is currently under construction. The State Oil Co. of Suriname (Staatsolie) is building the 34.4-mile, 14-in. pipeline to deliver crude oil from the Catharina Sophia field (Tambaredjo) to the Tout Lui Faut terminal near the capital, Paramaribo. Crude oil from the Jossi Kreek field will be injected at mile point (MP) 3.4. Oil from these two fields is now being moved to tout Lui Faut by Staatsolie-owned motorized ocean barges. Increased production to meet requirements of a planned refinery near Tout Lui Faut prompted the pipeline.

  14. A Survey of Visual Analytic Pipelines

    Institute of Scientific and Technical Information of China (English)

    Xu-Meng Wang; Tian-Ye Zhang; Yu-Xin Ma; Jing Xia; Wei Chen

    2016-01-01

    Visual analytics has been widely studied in the past decade. One key to make visual analytics practical for both research and industrial applications is the appropriate definition and implementation of the visual analytics pipeline which provides effective abstractions for designing and implementing visual analytics systems. In this paper we review the previous work on visual analytics pipelines and individual modules from multiple perspectives: data, visualization, model and knowledge. In each module we discuss various representations and descriptions of pipelines inside the module, and compare the commonalities and the differences among them.

  15. Management of a multi-product pipeline

    Energy Technology Data Exchange (ETDEWEB)

    Bettoli, R.; Iacovoni, A. [Nuovo Pignone S.p.A., Roma (Italy). Div. Sistemi Automazione; Holden, D. [LICconsult, Stockton-on-Tees (United Kingdom)

    1996-09-01

    The paper describes the SCADA (System Control and Data Acquisition) Tele-supervisory System for the Kandla-Bhatinda (KBPL) multi-product pipeline. The KBPL pipeline is 1,443 km in length; it is to carry petroleum products, in a batch cycle organization, from the Kandla foreshore terminal to Bhatinda. It consists of two inlet stations, four pumping stations, five delivery stations, and two terminal stations, and is equipped with a total of 85 block valves. All the stations have the capability for launching and receiving scrapers. The SCADA system consists of 10 Station Control Centers (SCC) and one Master Control Center (MCC), all located along the pipeline.

  16. Python Bindings for the Common Pipeline Library

    Science.gov (United States)

    Streicher, O.; Weilbacher, P. M.

    2012-09-01

    The Common Pipeline Library is a set of routines written by ESO to provide a standard interface for VLT instrument data reduction tasks (“pipelines”). To control these pipelines from Python, we developed a wrapper called PYTHON-CPL that allows one to conveniently work interactively and to process data as part of an automated data reduction system. The package will be used to implement the MUSE pipeline in the AstroWISE data management system. We describe the features and design of the package.

  17. 49 CFR 192.513 - Test requirements for plastic pipelines.

    Science.gov (United States)

    2010-10-01

    ... 49 Transportation 3 2010-10-01 2010-10-01 false Test requirements for plastic pipelines. 192.513 Section 192.513 Transportation Other Regulations Relating to Transportation (Continued) PIPELINE AND... Test requirements for plastic pipelines. (a) Each segment of a plastic pipeline must be tested...

  18. 75 FR 66425 - Pipeline Safety: Request for Special Permit

    Science.gov (United States)

    2010-10-28

    ... the Federal Pipeline Safety Laws, PHMSA is publishing this notice of a special permit request we have received from Gulf South Pipeline Company, LP, a natural gas pipeline operator, seeking relief from compliance with certain requirements in the Federal Pipeline Safety Regulations. This notice seeks public...

  19. 49 CFR 192.10 - Outer continental shelf pipelines.

    Science.gov (United States)

    2010-10-01

    ... 49 Transportation 3 2010-10-01 2010-10-01 false Outer continental shelf pipelines. 192.10 Section... NATURAL AND OTHER GAS BY PIPELINE: MINIMUM FEDERAL SAFETY STANDARDS General § 192.10 Outer continental shelf pipelines. Operators of transportation pipelines on the Outer Continental Shelf (as defined in...

  20. Vulnerability assessment of critical infrastructure : activity 2 progress report : information of SCADA systems and other security monitoring systems used in oil and gas pipelines

    Energy Technology Data Exchange (ETDEWEB)

    Gu, G.P. [Natural Resources Canada, Ottawa, ON (Canada). CANMET Materials Technology Laboratory

    2007-12-15

    Many pipelines are located in remote regions and subjected to harsh environmental conditions. Damage to pipelines can have significant economic and environmental impacts. This paper discussed the use of supervisory control and data acquisition (SCADA) systems to monitor and control oil and gas pipeline infrastructure. SCADA systems are a real time, distributed computerized system with an intelligent capability for condition identification and fault diagnosis. SCADA systems can be used to capture thousands of miles of pipeline system process data and distribute it to pipeline operators, whose work stations are networked with the SCADA central host computer. SCADA architectures include monolithic, distributed, and networked systems that can be distributed across wide area networks (WANs). SCADA security strategies must be implemented to ensure corporate network security. Case studies of SCADA systems currently used by oil and gas operators in Alberta were also presented. 15 refs., 1 fig.

  1. A homology-based pipeline for global prediction of post-translational modification sites

    Science.gov (United States)

    Chen, Xiang; Shi, Shao-Ping; Xu, Hao-Dong; Suo, Sheng-Bao; Qiu, Jian-Ding

    2016-05-01

    The pathways of protein post-translational modifications (PTMs) have been shown to play particularly important roles for almost any biological process. Identification of PTM substrates along with information on the exact sites is fundamental for fully understanding or controlling biological processes. Alternative computational strategies would help to annotate PTMs in a high-throughput manner. Traditional algorithms are suited for identifying the common organisms and tissues that have a complete PTM atlas or extensive experimental data. While annotation of rare PTMs in most organisms is a clear challenge. In this work, to this end we have developed a novel homology-based pipeline named PTMProber that allows identification of potential modification sites for most of the proteomes lacking PTMs data. Cross-promotion E-value (CPE) as stringent benchmark has been used in our pipeline to evaluate homology to known modification sites. Independent-validation tests show that PTMProber achieves over 58.8% recall with high precision by CPE benchmark. Comparisons with other machine-learning tools show that PTMProber pipeline performs better on general predictions. In addition, we developed a web-based tool to integrate this pipeline at http://bioinfo.ncu.edu.cn/PTMProber/index.aspx. In addition to pre-constructed prediction models of PTM, the website provides an extensional functionality to allow users to customize models.

  2. An image processing pipeline to detect and segment nuclei in muscle fiber microscopic images.

    Science.gov (United States)

    Guo, Yanen; Xu, Xiaoyin; Wang, Yuanyuan; Wang, Yaming; Xia, Shunren; Yang, Zhong

    2014-08-01

    Muscle fiber images play an important role in the medical diagnosis and treatment of many muscular diseases. The number of nuclei in skeletal muscle fiber images is a key bio-marker of the diagnosis of muscular dystrophy. In nuclei segmentation one primary challenge is to correctly separate the clustered nuclei. In this article, we developed an image processing pipeline to automatically detect, segment, and analyze nuclei in microscopic image of muscle fibers. The pipeline consists of image pre-processing, identification of isolated nuclei, identification and segmentation of clustered nuclei, and quantitative analysis. Nuclei are initially extracted from background by using local Otsu's threshold. Based on analysis of morphological features of the isolated nuclei, including their areas, compactness, and major axis lengths, a Bayesian network is trained and applied to identify isolated nuclei from clustered nuclei and artifacts in all the images. Then a two-step refined watershed algorithm is applied to segment clustered nuclei. After segmentation, the nuclei can be quantified for statistical analysis. Comparing the segmented results with those of manual analysis and an existing technique, we find that our proposed image processing pipeline achieves good performance with high accuracy and precision. The presented image processing pipeline can therefore help biologists increase their throughput and objectivity in analyzing large numbers of nuclei in muscle fiber images.

  3. An Optimized Informatics Pipeline for Mass Spectrometry-Based Peptidomics

    Science.gov (United States)

    Wu, Chaochao; Monroe, Matthew E.; Xu, Zhe; Slysz, Gordon W.; Payne, Samuel H.; Rodland, Karin D.; Liu, Tao; Smith, Richard D.

    2015-12-01

    The comprehensive MS analysis of the peptidome, the intracellular and intercellular products of protein degradation, has the potential to provide novel insights on endogenous proteolytic processing and its utility in disease diagnosis and prognosis. Along with the advances in MS instrumentation and related platforms, a plethora of proteomics data analysis tools have been applied for direct use in peptidomics; however, an evaluation of the currently available informatics pipelines for peptidomics data analysis has yet to be reported. In this study, we began by evaluating the results of several popular MS/MS database search engines, including MS-GF+, SEQUEST, and MS-Align+, for peptidomics data analysis, followed by identification and label-free quantification using the well-established accurate mass and time (AMT) tag and newly developed informed quantification (IQ) approaches, both based on direct LC-MS analysis. Our results demonstrated that MS-GF+ outperformed both SEQUEST and MS-Align+ in identifying peptidome peptides. Using a database established from MS-GF+ peptide identifications, both the AMT tag and IQ approaches provided significantly deeper peptidome coverage and less missing data for each individual data set than the MS/MS methods, while achieving robust label-free quantification. Besides having an excellent correlation with the AMT tag quantification results, IQ also provided slightly higher peptidome coverage. Taken together, we propose an optimized informatics pipeline combining MS-GF+ for initial database searching with IQ (or AMT tag) approaches for identification and label-free quantification for high-throughput, comprehensive, and quantitative peptidomics analysis.

  4. An Optimized Informatics Pipeline for Mass Spectrometry-Based Peptidomics

    Energy Technology Data Exchange (ETDEWEB)

    Wu, Chaochao; Monroe, Matthew E.; Xu, Zhe; Slysz, Gordon W.; Payne, Samuel H.; Rodland, Karin D.; Liu, Tao; Smith, Richard D.

    2015-12-26

    Comprehensive MS analysis of peptidome, the intracellular and intercellular products of protein degradation, has the potential to provide novel insights on endogenous proteolytic processing and their utility in disease diagnosis and prognosis. Along with the advances in MS instrumentation, a plethora of proteomics data analysis tools have been applied for direct use in peptidomics; however an evaluation of the currently available informatics pipelines for peptidomics data analysis has yet to be reported. In this study, we set off by evaluating the results of several popular MS/MS database search engines including MS-GF+, SEQUEST and MS-Align+ for peptidomics data analysis, followed by identification and label-free quantification using the well-established accurate mass and time (AMT) tag and newly developed informed quantification (IQ) approaches, both based on direct LC-MS analysis. Our result demonstrated that MS-GF+ outperformed both SEQUEST and MS-Align+ in identifying peptidome peptides. Using a database established from the MS-GF+ peptide identifications, both the AMT tag and IQ approaches provided significantly deeper peptidome coverage and less missing value for each individual data set than the MS/MS methods, while achieving robust label-free quantification. Besides having an excellent correlation with the AMT tag quantification results, IQ also provided slightly higher peptidome coverage than AMT. Taken together, we propose an optimal informatics pipeline combining MS-GF+ for initial database searching with IQ (or AMT) for identification and label-free quantification for high-throughput, comprehensive and quantitative peptidomics analysis.

  5. [Actinomycetes from mangrove and their secondary metabolites].

    Science.gov (United States)

    Hong, Kui

    2013-11-04

    Mangroves are woody plants located in tropical and subtropical intertidal coastal regions. Driven by the discovery of novel natural products from marine environment, mangrove is becoming a hot spot for actinomycetes resources collection and secondary metabolites (natural products) identification as well as their biosynthesis mechanism investigation. Salinaspora A produced by a Salinispora strain isolated from Bahamas mangrove environment, is in the first clinical trial. Till the time of writing this paper, 24 genera of 11 families and 8 suborders under the actinomycetale have been reported from mangrove, among which 3 are new genera, and 31 are new species. At the same time, secondary metabolites were identified from the mangrove actinomycetes culture, including alkanoids and quinines, azalomycins, antimycins, bezamides and quinazolines, divergolides, indole derivatives, kandenols, macrocyclic dilactones, and the attractive structures, such as the Streptocarbazoles, the multicyclic indolsesquiterpenes, and xiamycin presented unique structures. Their biosynthetic mechanism has also been investigated. Most of the metabolites were isolated from streptomycetes, with a few from Micromonospora and Saccharopolyspora.

  6. Identification of metabolites in urine and feces from rats dosed with the heterocyclic amine, 2-amino-3-methyl-9H-pyrido[2,3-b]indole (MeA alpha C)

    DEFF Research Database (Denmark)

    Frederiksen, H; Frandsen, H

    2004-01-01

    2-Amino-3-methyl-9H-pyrido[2,3-b]indole (MeA alpha C) is a proximate mutagenic and carcinogenic heterocyclic amine formed during ordinary cooking. In model systems, MeA alpha C can be formed by pyrolyses of either tryptophan or proteins of animal or vegetable origin. In the present study, the in ......2-Amino-3-methyl-9H-pyrido[2,3-b]indole (MeA alpha C) is a proximate mutagenic and carcinogenic heterocyclic amine formed during ordinary cooking. In model systems, MeA alpha C can be formed by pyrolyses of either tryptophan or proteins of animal or vegetable origin. In the present study......-metabolites was excreted during the first 24 h. Thirty-four percent of the dose was found in the rat urine samples collected to 24 h. In addition to unmetabolized MeA alpha C and two phase I metabolites, 6-OH-MeA alpha C and 7-OH-MeA alpha C, the following conjugated metabolites were identified: MeA alpha C-N(2......)-glucuronide, A alpha C-3-CH(2)O-glucuronide, 3-carboxy-A alpha C and 3-carboxy-A alpha C-glucuronide, and sulfate and glucuronide conjugates of 6-OH-MeA alpha C and 7-OH-MeA alpha C. Also, a large amount of a rather unstable compound proposed to be of MeA alpha C-N1-glucuronide was found. About 21...

  7. Isolation & Identification of an Actinomycetes Strain and Analysis of Its Metabolites%一株放线菌的分离鉴定及其代谢产物研究

    Institute of Scientific and Technical Information of China (English)

    杨帆; 陈良强; 林琳; 王和玉; 王莉

    2014-01-01

    利用高氏平板从酱香型白酒生产环境土壤中筛选分离得到1株放线菌NS01,利用形态学、16S rRNA序列同源性鉴定目的菌株为链霉菌属(Streptomyces sp.)。分别采用液态与固态培养基培养目的菌种,通过顶空固相微萃取技术进行萃取,再利用气相色谱质谱联用仪分析代谢产物,结果发现该菌代谢大量的萜烯类物质。代谢产物中的倍半萜烯类物质:2-甲基异莰醇、土臭素具有土臭味和霉味,该类物质可能与酱香型白酒酿造过程中出现霉味有关。%An actinomycetes strain NS01 was isolated from the soil in the production environment of Maotai by use of Gause's culture plate. And it was identified as Streptomyces sp. by 16S rRNA gene sequence analysis and morphological analysis. After the culture of strain NS01 by liquid culture medium and by solid culture medium respectively, its metabolites were extracted by HS-SPME and then analyzed by GC-MS. It was found that its metabolites contained a large number of terpenes. 2-methylisoborneol and geosmin in the sesquiterpenes in the metabolites might be relat ed to the musty-odor of base liquor.

  8. Liquid chromatography-high resolution/ high accuracy (tandem) mass spectrometry-based identification of in vivo generated metabolites of the selective androgen receptor modulator ACP-105 for doping control purposes.

    Science.gov (United States)

    Thevis, Mario; Thomas, Andreas; Piper, Thomas; Krug, Oliver; Delahaut, Philippe; Schänzer, Wilhelm

    2014-01-01

    Selective androgen receptor modulators (SARMs) represent an emerging class of therapeutics which have been prohibited in sport as anabolic agents according to the regulations of the World Anti-Doping Agency (WADA) since 2008. Within the past three years, numerous adverse analytical findings with SARMs in routine doping control samples have been reported despite missing clinical approval of these substances. Hence, preventive doping research concerning the metabolism and elimination of new therapeutic entities of the class of SARMs are vital for efficient and timely sports drug testing programs as banned compounds are most efficiently screened when viable targets (for example, characteristic metabolites) are identified. In the present study, the metabolism of ACP-105, a novel SARM drug candidate, was studied in vivo in rats. Following oral administration, urine samples were collected over a period of seven days and analyzed for metabolic products by Liquid chromatography-high resolution/high accuracy (tandem) mass spectrometry. Samples were subjected to enzymatic hydrolysis prior to liquid-liquid extraction and a total of seven major phase-I metabolites were detected, three of which were attributed to monohydroxylated and four to bishydroxylated ACP-105. The hydroxylation sites were assigned by means of diagnostic product ions and respective dissociation pathways of the analytes following positive or negative ionization and collisional activation as well as selective chemical derivatization. The identified metabolites were used as target compounds to investigate their traceability in a rat elimination urine samples study and monohydroxylated and bishydroxylated species were detectable for up to four and six days post-administration, respectively.

  9. Identification of a Classical Mutant in the Industrial Host Aspergillus niger by Systems Genetics: LaeA Is Required for Citric Acid Production and Regulates the Formation of Some Secondary Metabolites.

    Science.gov (United States)

    Niu, Jing; Arentshorst, Mark; Nair, P Deepa S; Dai, Ziyu; Baker, Scott E; Frisvad, Jens C; Nielsen, Kristian F; Punt, Peter J; Ram, Arthur F J

    2015-11-13

    The asexual filamentous fungus Aspergillus niger is an important industrial cell factory for citric acid production. In this study, we genetically characterized a UV-generated A. niger mutant that was originally isolated as a nonacidifying mutant, which is a desirable trait for industrial enzyme production. Physiological analysis showed that this mutant did not secrete large amounts of citric acid and oxalic acid, thus explaining the nonacidifying phenotype. As traditional complementation approaches to characterize the mutant genotype were unsuccessful, we used bulk segregant analysis in combination with high-throughput genome sequencing to identify the mutation responsible for the nonacidifying phenotype. Since A. niger has no sexual cycle, parasexual genetics was used to generate haploid segregants derived from diploids by loss of whole chromosomes. We found that the nonacidifying phenotype was caused by a point mutation in the laeA gene. LaeA encodes a putative methyltransferase-domain protein, which we show here to be required for citric acid production in an A. niger lab strain (N402) and in other citric acid production strains. The unexpected link between LaeA and citric acid production could provide new insights into the transcriptional control mechanisms related to citric acid production in A. niger. Interestingly, the secondary metabolite profile of a ΔlaeA strain differed from the wild-type strain, showing both decreased and increased metabolite levels, indicating that LaeA is also involved in regulating the production of secondary metabolites. Finally, we show that our systems genetics approach is a powerful tool to identify trait mutations. Copyright © 2016 Niu et al.

  10. Identification of a Classical Mutant in the Industrial Host Aspergillus niger by Systems Genetics: LaeA Is Required for Citric Acid Production and Regulates the Formation of Some Secondary Metabolites

    Directory of Open Access Journals (Sweden)

    Jing Niu

    2016-01-01

    Full Text Available The asexual filamentous fungus Aspergillus niger is an important industrial cell factory for citric acid production. In this study, we genetically characterized a UV-generated A. niger mutant that was originally isolated as a nonacidifying mutant, which is a desirable trait for industrial enzyme production. Physiological analysis showed that this mutant did not secrete large amounts of citric acid and oxalic acid, thus explaining the nonacidifying phenotype. As traditional complementation approaches to characterize the mutant genotype were unsuccessful, we used bulk segregant analysis in combination with high-throughput genome sequencing to identify the mutation responsible for the nonacidifying phenotype. Since A. niger has no sexual cycle, parasexual genetics was used to generate haploid segregants derived from diploids by loss of whole chromosomes. We found that the nonacidifying phenotype was caused by a point mutation in the laeA gene. LaeA encodes a putative methyltransferase-domain protein, which we show here to be required for citric acid production in an A. niger lab strain (N402 and in other citric acid production strains. The unexpected link between LaeA and citric acid production could provide new insights into the transcriptional control mechanisms related to citric acid production in A. niger. Interestingly, the secondary metabolite profile of a ΔlaeA strain differed from the wild-type strain, showing both decreased and increased metabolite levels, indicating that LaeA is also involved in regulating the production of secondary metabolites. Finally, we show that our systems genetics approach is a powerful tool to identify trait mutations.

  11. 75 FR 63774 - Pipeline Safety: Safety of On-Shore Hazardous Liquid Pipelines

    Science.gov (United States)

    2010-10-18

    ... an operator's Supervisory Control and Data Acquisition (SCADA) system for controlling the pipeline... activation timing, or methods for integration of EFRD operation with an operator's SCADA and leak...

  12. Pipelines in Louisiana, Geographic NAD83, USGS (1999) [pipelines_la_usgs_1999

    Data.gov (United States)

    Louisiana Geographic Information Center — This dataset contains vector line map information of various pipelines throughout the State of Louisiana. The vector data contain selected base categories of...

  13. Pipeline rules of thumb handbook a manual of quick, accurate solutions to everyday pipeline engineering problems

    CERN Document Server

    McAllister, EW

    2014-01-01

    Presented in easy-to-use, step-by-step order, Pipeline Rules of Thumb Handbook is a quick reference for day-to-day pipeline operations. For more than 35 years, the Pipeline Rules of Thumb Handbook has served as the ""go-to"" reference for solving even the most day-to-day vexing pipeline workflow problems. Now in its 8th edition, this handbook continues to set the standard by which all other piping books are judged. Along with over 30% new or updated material regarding codes, construction processes, and equipment, this book continues to offer hundreds of ""how-to"" methods and ha

  14. A Novel Method to Enhance Pipeline Trajectory Determination Using Pipeline Junctions.

    Science.gov (United States)

    Sahli, Hussein; El-Sheimy, Naser

    2016-04-21

    Pipeline inspection gauges (pigs) have been used for many years to perform various maintenance operations in oil and gas pipelines. Different pipeline parameters can be inspected during the pig journey. Although pigs use many sensors to detect the required pipeline parameters, matching these data with the corresponding pipeline location is considered a very important parameter. High-end, tactical-grade inertial measurement units (IMUs) are used in pigging applications to locate the detected problems of pipeline using other sensors, and to reconstruct the trajectories of the pig. These IMUs are accurate; however, their high cost and large sizes limit their use in small diameter pipelines (8″ or less). This paper describes a new methodology for the use of MEMS-based IMUs using an extended Kalman filter (EKF) and the pipeline junctions to increase the position parameters' accuracy and to reduce the total RMS errors even during the unavailability of above ground markers (AGMs). The results of this new proposed method using a micro-electro-mechanical systems (MEMS)-based IMU revealed that the position RMS errors were reduced by approximately 85% compared to the standard EKF solution. Therefore, this approach will enable the mapping of small diameter pipelines, which was not possible before.

  15. A Novel Method to Enhance Pipeline Trajectory Determination Using Pipeline Junctions

    Directory of Open Access Journals (Sweden)

    Hussein Sahli

    2016-04-01

    Full Text Available Pipeline inspection gauges (pigs have been used for many years to perform various maintenance operations in oil and gas pipelines. Different pipeline parameters can be inspected during the pig journey. Although pigs use many sensors to detect the required pipeline parameters, matching these data with the corresponding pipeline location is considered a very important parameter. High-end, tactical-grade inertial measurement units (IMUs are used in pigging applications to locate the detected problems of pipeline using other sensors, and to reconstruct the trajectories of the pig. These IMUs are accurate; however, their high cost and large sizes limit their use in small diameter pipelines (8″ or less. This paper describes a new methodology for the use of MEMS-based IMUs using an extended Kalman filter (EKF and the pipeline junctions to increase the position parameters’ accuracy and to reduce the total RMS errors even during the unavailability of above ground markers (AGMs. The results of this new proposed method using a micro-electro-mechanical systems (MEMS-based IMU revealed that the position RMS errors were reduced by approximately 85% compared to the standard EKF solution. Therefore, this approach will enable the mapping of small diameter pipelines, which was not possible before.

  16. Regular pipeline maintenance of gas pipeline using technical operational diagnostics methods

    Energy Technology Data Exchange (ETDEWEB)

    Volentic, J. [Gas Transportation Department, Slovensky plynarensky priemysel, Slovak Gas Industry, Bratislava (Slovakia)

    1997-12-31

    Slovensky plynarensky priemysel (SPP) has operated 17 487 km of gas pipelines in 1995. The length of the long-line pipelines reached 5 191 km, distribution network was 12 296 km. The international transit system of long-line gas pipelines ranged 1 939 km of pipelines of various dimensions. The described scale of transport and distribution system represents a multibillion investments stored in the ground, which are exposed to the environmental influences and to pipeline operational stresses. In spite of all technical and maintenance arrangements, which have to be performed upon operating gas pipelines, the gradual ageing takes place anyway, expressed in degradation process both in steel tube, as well as in the anti-corrosion coating. Within a certain time horizon, a consistent and regular application of methods and means of in-service technical diagnostics and rehabilitation of existing pipeline systems make it possible to save substantial investment funds, postponing the need in funds for a complex or partial reconstruction or a new construction of a specific gas section. The purpose of this presentation is to report on the implementation of the programme of in-service technical diagnostics of gas pipelines within the framework of regular maintenance of SPP s.p. Bratislava high pressure gas pipelines. (orig.) 6 refs.

  17. Oil and gas pipelines in nontechnical language

    National Research Council Canada - National Science Library

    Miesner, Thomas O; Leffler, William L

    2006-01-01

    Oil & Gas Pipelines in Nontechnical Language examines the processes, techniques, equipment, and facilities used to transport fluids such as refined products, crude oil, natural gas, and natural gas liquids...

  18. Communication systems vital to Colombian pipeline

    Energy Technology Data Exchange (ETDEWEB)

    Serrato, E. [Ecopetrol, Bogota (Colombia); Mailloux, R. [Bristol Babcock Inc., Watertown, CT (United States)

    1997-02-01

    Construction of the Centro Oriente Gas Pipeline represents a major step in Colombia`s goal to strengthen the emerging natural gas business. With construction beginning in 1995, the Centro Oriente is scheduled to begin operation early this year transporting 150 MMcf/d. The 779-kilometer (484-mile) pipeline ranging in diameter from 22-inch to 12-inches, provides the central transportation link between major gas suppliers in both the northern and western regions of Colombia and new markets throughout their immediate regions as well as in the central and eastern regions. TransCanada, operating company for the Centro Oriente pipeline, will develop and manage the support organizations required to operate and maintain the system. The central control system for the CPC is the Gas SCADA system, ADACS, provided by Bristol Babcock Inc. (BBI). This control system provides the data acquisition and control capabilities necessary to operate the entire pipeline safely and efficiently from Burcaramanga.

  19. Citizenship program in near communities of pipelines

    Energy Technology Data Exchange (ETDEWEB)

    Mascarenhas, Carina R.; Vilas Boas, Ianne P. [TELSAN Engenharia, Belo Horizonte, MG (Brazil); Bourscheid, Pitagoras [PETROBRAS S.A., Rio de Janeiro, RJ (Brazil)

    2009-12-19

    During the construction of a pipeline, the IENE - Engineering Unit of PETROBRAS, responsible for the construction and erection of pipelines and related plants in northeastern Brazil, crossed more than 7 states and 250 counties, had implemented a social responsibility program, in special a citizenship program. This action was the result of community studies located near of the pipelines AID - Direct Influence Area (438 yards right and left of the pipeline) and through the evidence that those locations were poor and have no personal documents and citizen position in society. This paper intents to share the experience of IENE about its citizen program that worked in three big lines: community mobilization; citizenship qualification; and citizenship board. This last one, turns possible to people obtains theirs personal documents and exercise the plenitude of citizenship. (author)

  20. Sinopec Fuels Development of Pipelines in East China

    Institute of Scientific and Technical Information of China (English)

    Li Xuemei

    2004-01-01

    @@ Crude pipeline completed in Yangtze River Delta The Ningbo-Shanghai-Nanjing crude pipeline was recently wound up for construction following completion of the subsea segment in Hangzhou Bay,the last part of the pipeline. The 711 mm-diameter crude pipeline, designed and constructed by Sinopec, adopts the advanced SCADA system for full automation control. The pipeline is designed to have an annual crude transmission capacity of 20million tons.

  1. 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...

  2. Developing Pipeline Transportation in West China

    Institute of Scientific and Technical Information of China (English)

    Yang Chenghan; Wang Wei

    1997-01-01

    @@ Since the late 1980s, focus of exploration and development for oil & gas has been diverted to thewest of China, resulting in the discovery and development of Shaanbei gas field followed by large-scale exploration and development of Tarim,Turpan and Hami basins. Responding to this situation, pipeline construction focus has also been transferred to west China where large-scale development of pipeline transportation, an opportunity as well as a challenge, is expected.

  3. Astronomical pipeline processing using fuzzy logic

    Science.gov (United States)

    Shamir, Lior

    In the past few years, pipelines providing astronomical data have been becoming increasingly important. The wide use of robotic telescopes has provided significant discoveries, and sky survey projects such as SDSS and the future LSST are now considered among the premier projects in the field astronomy. The huge amount of data produced by these pipelines raises the need for automatic processing. Astronomical pipelines introduce several well-defined problems such as astronomical image compression, cosmic-ray hit rejection, transient detection, meteor triangulation and association of point sources with their corresponding known stellar objects. We developed and applied soft computing algorithms that provide new or improved solutions to these growing problems in the field of pipeline processing of astronomical data. One new approach that we use is fuzzy logic-based algorithms, which enables the automatic analysis of the astronomical pipelines and allows mining the data for not-yet-known astronomical discoveries such as optical transients and variable stars. The developed algorithms have been tested with excellent results on the NightSkyLive sky survey, which provides a pipeline of 150 astronomical pictures per hour, and covers almost the entire global night sky.

  4. Consensus between pipelines in structural brain networks.

    Directory of Open Access Journals (Sweden)

    Christopher S Parker

    Full Text Available Structural brain networks may be reconstructed from diffusion MRI tractography data and have great potential to further our understanding of the topological organisation of brain structure in health and disease. Network reconstruction is complex and involves a series of processesing methods including anatomical parcellation, registration, fiber orientation estimation and whole-brain fiber tractography. Methodological choices at each stage can affect the anatomical accuracy and graph theoretical properties of the reconstructed networks, meaning applying different combinations in a network reconstruction pipeline may produce substantially different networks. Furthermore, the choice of which connections are considered important is unclear. In this study, we assessed the similarity between structural networks obtained using two independent state-of-the-art reconstruction pipelines. We aimed to quantify network similarity and identify the core connections emerging most robustly in both pipelines. Similarity of network connections was compared between pipelines employing different atlases by merging parcels to a common and equivalent node scale. We found a high agreement between the networks across a range of fiber density thresholds. In addition, we identified a robust core of highly connected regions coinciding with a peak in similarity across network density thresholds, and replicated these results with atlases at different node scales. The binary network properties of these core connections were similar between pipelines but showed some differences in atlases across node scales. This study demonstrates the utility of applying multiple structural network reconstrution pipelines to diffusion data in order to identify the most important connections for further study.

  5. The "PepSAVI-MS" Pipeline for Natural Product Bioactive Peptide Discovery.

    Science.gov (United States)

    Kirkpatrick, Christine L; Broberg, Christopher A; McCool, Elijah N; Lee, Woo Jean; Chao, Alex; McConnell, Evan W; Pritchard, David A; Hebert, Michael; Fleeman, Renee; Adams, Jessie; Jamil, Amer; Madera, Laurence; Strömstedt, Adam A; Göransson, Ulf; Liu, Yufeng; Hoskin, David W; Shaw, Lindsey N; Hicks, Leslie M

    2017-01-17

    The recent increase in extensively drug-resistant bacterial pathogens and the associated increase of morbidity and mortality demonstrate the immediate need for new antibiotic backbones with novel mechanisms of action. Here, we report the development of the PepSAVI-MS pipeline for bioactive peptide discovery. This highly versatile platform employs mass spectrometry and statistics to identify bioactive peptide targets from complex biological samples. We validate the use of this platform through the successful identification of known bioactive peptides from a botanical species, Viola odorata. Using this pipeline, we have widened the known antimicrobial spectrum for V. odorata cyclotides, including antibacterial activity of cycloviolacin O2 against A. baumannii. We further demonstrate the broad applicability of the platform through the identification of novel anticancer activities for cycloviolacins by their cytotoxicity against ovarian, breast, and prostate cancer cell lines.

  6. Identification of metabolites in urine and feces from rats dosed with the heterocyclic amine, 2-amino-3-methyl-9H-pyrido[2,3-b]indole (MeA alpha C)

    DEFF Research Database (Denmark)

    Frederiksen, H.; Frandsen, Henrik Lauritz

    2004-01-01

    2-Amino-3-methyl-9H-pyrido[2,3-b]indole (MeAalphaC) is a proximate mutagenic and carcinogenic heterocyclic amine formed during ordinary cooking. In model systems, MeAalphaC can be formed by pyrolyses of either tryptophan or proteins of animal or vegetable origin. In the present study, the in vivo...... the first 24 h. Thirty-four percent of the dose was found in the rat urine samples collected to 24 h. In addition to unmetabolized MeAalphaC and two phase I metabolites, 6-OH-MeAalphaC and 7-OH-MeAalphaC, the following conjugated metabolites were identified: MeAalphaC-N-2-glucuronide, AalphaC-3-CH2O......-glucuronide, 3-carboxy-AalphaC and 3-carboxy-AalphaC-glucuronide, and sulfate and glucuronide conjugates of 6-OH-MeAalphaC and 7-OH-MeAalphaC. Also, a large amount of a rather unstable compound proposed to be of MeAalphaC-N1-glucuronide was found. About 21% of the dose was excreted in feces during the first 24 h...

  7. Optimization of operational flow rates of an oil pipeline on the basis of a linear regression model

    Energy Technology Data Exchange (ETDEWEB)

    Smati, A.; Djelloul, A. (Institut National des Hydrocarbures et de la Chimie, Boumerdes (Algeria))

    Many uncontrollable factors cause random fluctuations in the properties of an oil pipeline. After a brief statistical analysis of the leading parameters used to identify the phenomenon, this article describes an optimization algorithm for minimizing energy consumption in pumping stations. The proposed algorithm is based on a linear regression model. Several very flexible approaches to multivariable identification are examined.

  8. Mining Bacterial Genomes for Secondary Metabolite Gene Clusters.

    Science.gov (United States)

    Adamek, Martina; Spohn, Marius; Stegmann, Evi; Ziemert, Nadine

    2017-01-01

    With the emergence of bacterial resistance against frequently used antibiotics, novel antibacterial compounds are urgently needed. Traditional bioactivity-guided drug discovery strategies involve laborious screening efforts and display high rediscovery rates. With the progress in next generation sequencing methods and the knowledge that the majority of antibiotics in clinical use are produced as secondary metabolites by bacteria, mining bacterial genomes for secondary metabolites with antimicrobial activity is a promising approach, which can guide a more time and cost-effective identification of novel compounds. However, what sounds easy to accomplish, comes with several challenges. To date, several tools for the prediction of secondary metabolite gene clusters are available, some of which are based on the detection of signature genes, while others are searching for specific patterns in gene content or regulation.Apart from the mere identification of gene clusters, several other factors such as determining cluster boundaries and assessing the novelty of the detected cluster are important. For this purpose, comparison of the predicted secondary metabolite genes with different cluster and compound databases is necessary. Furthermore, it is advisable to classify detected clusters into gene cluster families. So far, there is no standardized procedure for genome mining; however, different approaches to overcome all of these challenges exist and are addressed in this chapter. We give practical guidance on the workflow for secondary metabolite gene cluster identification, which includes the determination of gene cluster boundaries, addresses problems occurring with the use of draft genomes, and gives an outlook on the different methods for gene cluster classification. Based on comprehensible examples a protocol is set, which should enable the readers to mine their own genome data for interesting secondary metabolites.

  9. Black powder in gas pipelines

    Energy Technology Data Exchange (ETDEWEB)

    Sherik, Abdelmounam [Saudi Aramco, Dhahran (Saudi Arabia)

    2009-07-01

    Despite its common occurrence in the gas industry, black powder is a problem that is not well understood across the industry, in terms of its chemical and physical properties, source, formation, prevention or management of its impacts. In order to prevent or effectively manage the impacts of black powder, it is essential to have knowledge of its chemical and physical properties, formation mechanisms and sources. The present paper is divided into three parts. The first part of this paper is a synopsis of published literature. The second part reviews the recent laboratory and field work conducted at Saudi Aramco Research and Development Center to determine the compositions, properties, sources and formation mechanisms of black powder in gas transmission systems. Microhardness, nano-indentation, X-ray Diffraction (XRD), X-ray Fluorescence (XRF) and Scanning Electron Microscopy (SEM) techniques were used to analyze a large number of black powder samples collected from the field. Our findings showed that black powder is generated inside pipelines due to internal corrosion and that the composition of black powder is dependent on the composition of transported gas. The final part presents a summary and brief discussion of various black powder management methods. (author)

  10. Automated pipelines for spectroscopic analysis

    Science.gov (United States)

    Allende Prieto, C.

    2016-09-01

    The Gaia mission will have a profound impact on our understanding of the structure and dynamics of the Milky Way. Gaia is providing an exhaustive census of stellar parallaxes, proper motions, positions, colors and radial velocities, but also leaves some glaring holes in an otherwise complete data set. The radial velocities measured with the on-board high-resolution spectrograph will only reach some 10 % of the full sample of stars with astrometry and photometry from the mission, and detailed chemical information will be obtained for less than 1 %. Teams all over the world are organizing large-scale projects to provide complementary radial velocities and chemistry, since this can now be done very efficiently from the ground thanks to large and mid-size telescopes with a wide field-of-view and multi-object spectrographs. As a result, automated data processing is taking an ever increasing relevance, and the concept is applying to many more areas, from targeting to analysis. In this paper, I provide a quick overview of recent, ongoing, and upcoming spectroscopic surveys, and the strategies adopted in their automated analysis pipelines.

  11. The Ruptured Pipeline: Analysis of the Mining Engineering Faculty Pipeline

    Science.gov (United States)

    Poulton, M.

    2011-12-01

    The booming commodities markets of the past seven years have created an enormous demand for economic geologists, mining engineers, and extractive metallurgists. The mining sector has largely been recession proof due to demand drivers coming from developing rather than developed nations. The strong demand for new hires as well as mid-career hires has exposed the weakness of the U.S. university supply pipeline for these career fields. A survey of mining and metallurgical engineering faculty and graduate students was conducted in 2010 at the request of the Society for Mining, Metallurgy, and Exploration. The goals of the surveys were to determine the demographics of the U.S. faculty in mining and metallurgical engineering, the expected faculty turn over by 2010 and the potential supply of graduate students as the future professorate. All Mining Engineering and Metallurgical Engineering degrees in the U.S. are accredited by the Accreditation Board for Engineering and Technology (ABET) and the specific courses required are set by the sponsoring professional society, Society for Mining, Metallurgy, and Exploration. There are 13 universities in the U.S. that offer a degree in Mining Engineering accredited as Mining Engineering and 1 university that grants a Mining Engineering degree accredited under general engineering program requirements. Faculty numbers are approximately 87 tenure track positions with a total undergraduate enrollment of slightly over 1,000 in the 2008-2009 academic year. There are approximately 262 graduate students in mining engineering in the U.S. including 87 Ph.D. students. Mining Engineering department heads have identified 14 positions open in 2010 and 18 positions expected to be open in the next 5 years and an additional 21 positions open by 2020. The current survey predicts a 56% turn over in mining faculty ranks over the next 10 years but a retirement of 100% of senior faculty over 10 years. 63% of graduate students say they are interested in

  12. PGPB's pipeline integrity management system

    Energy Technology Data Exchange (ETDEWEB)

    Urencio, Claudio; Sanchez, Luis; Moreno, Carlos [PGPB - Pemex Gas y Petroquimica Basica (Mexico)

    2005-07-01

    Pemex Gas has 12,134 km of natural gas transmission pipelines, 1,835 Km for LPG and 1,216 Km for basic petrochemicals. The must part of this infrastructure was built in the 70's and reaching their 35 years of operating life. To manage the integrity of the three systems, Pemex Gas has a portfolio of technological tools. This tools allow the Company to improves the decision taking, align the budget with their strategic goals, achieve efficient asset utilization, and increase the value generation. The process of integrity management starts with the risk evaluation on assets, with the use of a software called IAP (Integrity Assessment Program). This information is integrated to the SIIA (Assets Identification System). The results of both software are used to the construction of the Risk Atlas, which identifies graphically each pipeline segment, with their related risk and factors that influence their behavior. The Risk Atlas gives us information about the consequences to the people, environment and facilities, so we can design customized plans to prevent or mitigate emergencies. Finally a detailed analysis of the resulting information and scenarios simulations help us to determine the best investment projects that will minimize the risk through all our assets. (author)

  13. PANGEA: pipeline for analysis of next generation amplicons.

    Science.gov (United States)

    Giongo, Adriana; Crabb, David B; Davis-Richardson, Austin G; Chauliac, Diane; Mobberley, Jennifer M; Gano, Kelsey A; Mukherjee, Nabanita; Casella, George; Roesch, Luiz F W; Walts, Brandon; Riva, Alberto; King, Gary; Triplett, Eric W

    2010-07-01

    High-throughput DNA sequencing can identify organisms and describe population structures in many environmental and clinical samples. Current technologies generate millions of reads in a single run, requiring extensive computational strategies to organize, analyze and interpret those sequences. A series of bioinformatics tools for high-throughput sequencing analysis, including pre-processing, clustering, database matching and classification, have been compiled into a pipeline called PANGEA. The PANGEA pipeline was written in Perl and can be run on Mac OSX, Windows or Linux. With PANGEA, sequences obtained directly from the sequencer can be processed quickly to provide the files needed for sequence identification by BLAST and for comparison of microbial communities. Two different sets of bacterial 16S rRNA sequences were used to show the efficiency of this workflow. The first set of 16S rRNA sequences is derived from various soils from Hawaii Volcanoes National Park. The second set is derived from stool samples collected from diabetes-resistant and diabetes-prone rats. The workflow described here allows the investigator to quickly assess libraries of sequences on personal computers with customized databases. PANGEA is provided for users as individual scripts for each step in the process or as a single script where all processes, except the chi(2) step, are joined into one program called the 'backbone'.

  14. Redefining the Data Pipeline Using GPUs

    Science.gov (United States)

    Warner, C.; Eikenberry, S. S.; Gonzalez, A. H.; Packham, C.

    2013-10-01

    There are two major challenges facing the next generation of data processing pipelines: 1) handling an ever increasing volume of data as array sizes continue to increase and 2) the desire to process data in near real-time to maximize observing efficiency by providing rapid feedback on data quality. Combining the power of modern graphics processing units (GPUs), relational database management systems (RDBMSs), and extensible markup language (XML) to re-imagine traditional data pipelines will allow us to meet these challenges. Modern GPUs contain hundreds of processing cores, each of which can process hundreds of threads concurrently. Technologies such as Nvidia's Compute Unified Device Architecture (CUDA) platform and the PyCUDA (http://mathema.tician.de/software/pycuda) module for Python allow us to write parallel algorithms and easily link GPU-optimized code into existing data pipeline frameworks. This approach has produced speed gains of over a factor of 100 compared to CPU implementations for individual algorithms and overall pipeline speed gains of a factor of 10-25 compared to traditionally built data pipelines for both imaging and spectroscopy (Warner et al., 2011). However, there are still many bottlenecks inherent in the design of traditional data pipelines. For instance, file input/output of intermediate steps is now a significant portion of the overall processing time. In addition, most traditional pipelines are not designed to be able to process data on-the-fly in real time. We present a model for a next-generation data pipeline that has the flexibility to process data in near real-time at the observatory as well as to automatically process huge archives of past data by using a simple XML configuration file. XML is ideal for describing both the dataset and the processes that will be applied to the data. Meta-data for the datasets would be stored using an RDBMS (such as mysql or PostgreSQL) which could be easily and rapidly queried and file I/O would be

  15. Overview of interstate hydrogen pipeline systems.

    Energy Technology Data Exchange (ETDEWEB)

    Gillette, J .L.; Kolpa, R. L

    2008-02-01

    The use of hydrogen in the energy sector of the United States is projected to increase significantly in the future. Current uses are predominantly in the petroleum refining sector, with hydrogen also being used in the manufacture of chemicals and other specialized products. Growth in hydrogen consumption is likely to appear in the refining sector, where greater quantities of hydrogen will be required as the quality of the raw crude decreases, and in the mining and processing of tar sands and other energy resources that are not currently used at a significant level. Furthermore, the use of hydrogen as a transportation fuel has been proposed both by automobile manufacturers and the federal government. Assuming that the use of hydrogen will significantly increase in the future, there would be a corresponding need to transport this material. A variety of production technologies are available for making hydrogen, and there are equally varied raw materials. Potential raw materials include natural gas, coal, nuclear fuel, and renewables such as solar, wind, or wave energy. As these raw materials are not uniformly distributed throughout the United States, it would be necessary to transport either the raw materials or the hydrogen long distances to the appropriate markets. While hydrogen may be transported in a number of possible forms, pipelines currently appear to be the most economical means of moving it in large quantities over great distances. One means of controlling hydrogen pipeline costs is to use common rights-of-way (ROWs) whenever feasible. For that reason, information on hydrogen pipelines is the focus of this document. Many of the features of hydrogen pipelines are similar to those of natural gas pipelines. Furthermore, as hydrogen pipeline networks expand, many of the same construction and operating features of natural gas networks would be replicated. As a result, the description of hydrogen pipelines will be very similar to that of natural gas pipelines

  16. 77 FR 6857 - Pipeline Safety: Notice of Public Meetings on Improving Pipeline Leak Detection System...

    Science.gov (United States)

    2012-02-09

    ... and Research 5:45 p.m. Wrap-Up/Next Steps 6 p.m. Adjournment Preliminary Agenda for the Public Meeting... Pipelines 12:30 p.m. Lunch 2 p.m. Panel 3: Valve Capabilities, Limitations and Research 4 p.m. Wrap-Up/Next... Administrator for Pipeline Safety. BILLING CODE 4910-60-P...

  17. The Dangers of Pipeline Thinking: How the School-to-Prison Pipeline Metaphor Squeezes out Complexity

    Science.gov (United States)

    McGrew, Ken

    2016-01-01

    In this essay Ken McGrew critically examines the "school-to-prison pipeline" metaphor and associated literature. The origins and influence of the metaphor are compared with the origins and influence of the competing "prison industrial complex" concept. Specific weaknesses in the "pipeline literature" are examined.…

  18. 77 FR 66830 - LNG Development Company, LLC and Oregon Pipeline Company; Northwest Pipeline GP; Notice of...

    Science.gov (United States)

    2012-11-07

    ... Energy Regulatory Commission LNG Development Company, LLC and Oregon Pipeline Company; Northwest Pipeline GP; Notice of Extension of Comment Period for the Oregon LNG Export and Washington Expansion Projects This notice announces the extension of the public scoping process and comment period for the Oregon...

  19. 75 FR 4134 - Pipeline Safety: Leak Detection on Hazardous Liquid Pipelines

    Science.gov (United States)

    2010-01-26

    ... safety study on pipeline Supervisory Control and Data Acquisition (SCADA) systems (NTSB/SS-05/02). The... indications of a leak on the SCADA interface was the impetus for this study. The NTSB examined 13 hazardous... large pipeline breaks. The line balance processes incorporating SCADA or other technology are geared...

  20. 78 FR 41991 - Pipeline Safety: Potential for Damage to Pipeline Facilities Caused by Flooding

    Science.gov (United States)

    2013-07-12

    ... gallons of crude oil into the Yellowstone River. The rupture was caused by debris washing downstream in... structure and by impact and/or waterborne forces. Washouts and erosion may result in loss of support for both buried and exposed pipelines. The flow of water against an exposed pipeline may also result...

  1. Marine Environmental Protection and Transboundary Pipeline Projects: A Case Study of the Nord Stream Pipeline

    NARCIS (Netherlands)

    Lott, Alexander

    2011-01-01

    The Nord Stream transboundary submarine pipeline, significant for its impact on the EU energy policy, has been a heav- ily debated issue in the Baltic Sea region during the past decade. This is partly due to the concerns over the effects that the pipeline might have on the Baltic Sea as a particular

  2. 76 FR 29333 - Pipeline Safety: Meetings of the Technical Pipeline Safety Standards Committee and the Technical...

    Science.gov (United States)

    2011-05-20

    ... staff to assist in the creation of a pipeline safety report to the nation. The subcommittee is made up...) and the creation of a subcommittee to assist PHMSA in the preparation of a pipeline safety report to the nation. PHMSA will host a series of meetings with a newly formed subcommittee to review and...

  3. 77 FR 61825 - Pipeline Safety: Notice of Public Meeting on Pipeline Data

    Science.gov (United States)

    2012-10-11

    ... (NAPSR) are sponsoring this public meeting to discuss how pipeline data is currently used by stakeholders... public meeting on pipeline data will be held on Monday, October 29, 2012, from 1 p.m. to 5:30 p.m. and... meeting are to: 1. Determine how stakeholders, including PHMSA, industry, and the public use the data....

  4. Pipeline design software and the simulation of liquid propane/butane-light oils pipeline operations

    Energy Technology Data Exchange (ETDEWEB)

    Peters, J. [Monenco AGRA Inc., Calgary, Alberta (Canada)

    1996-12-31

    A comprehensive and integrated suite of computer software routines has been developed to simulate the flow of liquids in pipelines. The fluid properties module accommodates Newtonian and non-Newtonian liquids or mixtures including corrections for changes in properties with temperature and pressure. The hydraulic model calculates pressure drop in single or looped pipelines based on the diameter, route (length) and profile data provided. For multi-product pipelines the hydraulics module estimates energy loss for any sequence of batches given the size and fluid properties of each batch, and the velocity in the pipeline. When the characteristics of existing or proposed pipeline pumps are included, location and size of pumps can be optimized. The effect of heat loss on pressure drop is predicted by invoking the module which calculates the fluid temperature profile based on operating conditions, fluid properties, pipe and insulation conductivity and soil heat transfer data. Modules, created to simulate heater or cooler operations, can be incorporated to compensate for changes in temperature. Input data and calculated results can be presented in a format customized by the user. The simulation software has been successfully applied to multi-product, fuel oil, and non-Newtonian emulsion pipelines. The simulation and operation of a refinery products pipeline for the transportation of propane, butane, gasline, jet and diesel batches will be discussed. The impact of high vapor pressure batches (i.e., propane and butane) on the operation of the pipeline and on the upstream and downstream facilities will be examined in detail.

  5. 77 FR 45417 - Pipeline Safety: Inspection and Protection of Pipeline Facilities After Railway Accidents

    Science.gov (United States)

    2012-07-31

    ... Pipeline Facilities After Railway Accidents AGENCY: Pipeline and Hazardous Materials Safety Administration... either during a railroad accident or other event occurring in the right-of-way. Further, the advisory... to identify and notify underground utilities that an incident has occurred in the vicinity of their...

  6. Development of fungal cell factories for the production of secondary metabolites: Linking genomics and metabolism

    Directory of Open Access Journals (Sweden)

    Jens Christian Nielsen

    2017-03-01

    Full Text Available The genomic era has revolutionized research on secondary metabolites and bioinformatics methods have in recent years revived the antibiotic discovery process after decades with only few new active molecules being identified. New computational tools are driven by genomics and metabolomics analysis, and enables rapid identification of novel secondary metabolites. To translate this increased discovery rate into industrial exploitation, it is necessary to integrate secondary metabolite pathways in the metabolic engineering process. In this review, we will describe the novel advances in discovery of secondary metabolites produced by filamentous fungi, highlight the utilization of genome-scale metabolic models (GEMs in the design of fungal cell factories for the production of secondary metabolites and review strategies for optimizing secondary metabolite production through the construction of high yielding platform cell factories.

  7. Novel R pipeline for analyzing Biolog Phenotypic MicroArray data.

    Directory of Open Access Journals (Sweden)

    Minna Vehkala

    Full Text Available Data produced by Biolog Phenotype MicroArrays are longitudinal measurements of cells' respiration on distinct substrates. We introduce a three-step pipeline to analyze phenotypic microarray data with novel procedures for grouping, normalization and effect identification. Grouping and normalization are standard problems in the analysis of phenotype microarrays defined as categorizing bacterial responses into active and non-active, and removing systematic errors from the experimental data, respectively. We expand existing solutions by introducing an important assumption that active and non-active bacteria manifest completely different metabolism and thus should be treated separately. Effect identification, in turn, provides new insights into detecting differing respiration patterns between experimental conditions, e.g. between different combinations of strains and temperatures, as not only the main effects but also their interactions can be evaluated. In the effect identification, the multilevel data are effectively processed by a hierarchical model in the Bayesian framework. The pipeline is tested on a data set of 12 phenotypic plates with bacterium Yersinia enterocolitica. Our pipeline is implemented in R language on the top of opm R package and is freely available for research purposes.

  8. Novel R pipeline for analyzing Biolog Phenotypic MicroArray data.

    Science.gov (United States)

    Vehkala, Minna; Shubin, Mikhail; Connor, Thomas R; Thomson, Nicholas R; Corander, Jukka

    2015-01-01

    Data produced by Biolog Phenotype MicroArrays are longitudinal measurements of cells' respiration on distinct substrates. We introduce a three-step pipeline to analyze phenotypic microarray data with novel procedures for grouping, normalization and effect identification. Grouping and normalization are standard problems in the analysis of phenotype microarrays defined as categorizing bacterial responses into active and non-active, and removing systematic errors from the experimental data, respectively. We expand existing solutions by introducing an important assumption that active and non-active bacteria manifest completely different metabolism and thus should be treated separately. Effect identification, in turn, provides new insights into detecting differing respiration patterns between experimental conditions, e.g. between different combinations of strains and temperatures, as not only the main effects but also their interactions can be evaluated. In the effect identification, the multilevel data are effectively processed by a hierarchical model in the Bayesian framework. The pipeline is tested on a data set of 12 phenotypic plates with bacterium Yersinia enterocolitica. Our pipeline is implemented in R language on the top of opm R package and is freely available for research purposes.

  9. Federal regulation of the pipeline industry: a summary review. [Effects on use of energy-conservation technology

    Energy Technology Data Exchange (ETDEWEB)

    Banks, W. F.

    1977-05-31

    The principal purposes of this report are: (1) identification of the jurisdiction areas of the Federal pipeline-regulating agencies, and (2) examination of the amenability of the regulatory system to the introduction of energy-conservative new technology into the pipeline industry. The history, scope, and agency structure of state and Federal regulation are recounted and some gaps, overlaps, and ambiguities are identified. The only significant inhibitory effects upon technological innovation are found to derive from the FPC and ICC limits upon profit, the 1941 Justice Department consent decree limiting dividends to shipper-owned pipelines, and the income tax rules governing recovery of investment credits and startup losses. Effects of these limits are explored by simulation studies using the Systems, Science and Software pipeline economic model (PEM). Two new concepts of regulation are proposed which would neutralize the inhibitory effect of the present regulatory system and would motivate pipeline operators to conserve energy: (1) use of a ''national equivalent value'' in the economic tradeoff analyses which justify entry of a technological innovation into the rate base (valuation), and (2) a ''valuation allowance'' which would reverse the presently often-existing situation and insure that the pipeline operator would realize a greater profit from saving energy than from wasting it.

  10. A Proposed Scalable Design and Simulation of Wireless Sensor Network-Based Long-Distance Water Pipeline Leakage Monitoring System

    Directory of Open Access Journals (Sweden)

    Abdulaziz S. Almazyad

    2014-02-01

    Full Text Available Anomalies such as leakage and bursts in water pipelines have severe consequences for the environment and the economy. To ensure the reliability of water pipelines, they must be monitored effectively. Wireless Sensor Networks (WSNs have emerged as an effective technology for monitoring critical infrastructure such as water, oil and gas pipelines. In this paper, we present a scalable design and simulation of a water pipeline leakage monitoring system using Radio Frequency IDentification (RFID and WSN technology. The proposed design targets long-distance aboveground water pipelines that have special considerations for maintenance, energy consumption and cost. The design is based on deploying a group of mobile wireless sensor nodes inside the pipeline and allowing them to work cooperatively according to a prescheduled order. Under this mechanism, only one node is active at a time, while the other nodes are sleeping. The node whose turn is next wakes up according to one of three wakeup techniques: location-based, time-based and interrupt-driven. In this paper, mathematical models are derived for each technique to estimate the corresponding energy consumption and memory size requirements. The proposed equations are analyzed and the results are validated using simulation.

  11. A proposed scalable design and simulation of wireless sensor network-based long-distance water pipeline leakage monitoring system.

    Science.gov (United States)

    Almazyad, Abdulaziz S; Seddiq, Yasser M; Alotaibi, Ahmed M; Al-Nasheri, Ahmed Y; BenSaleh, Mohammed S; Obeid, Abdulfattah M; Qasim, Syed Manzoor

    2014-02-20

    Anomalies such as leakage and bursts in water pipelines have severe consequences for the environment and the economy. To ensure the reliability of water pipelines, they must be monitored effectively. Wireless Sensor Networks (WSNs) have emerged as an effective technology for monitoring critical infrastructure such as water, oil and gas pipelines. In this paper, we present a scalable design and simulation of a water pipeline leakage monitoring system using Radio Frequency IDentification (RFID) and WSN technology. The proposed design targets long-distance aboveground water pipelines that have special considerations for maintenance, energy consumption and cost. The design is based on deploying a group of mobile wireless sensor nodes inside the pipeline and allowing them to work cooperatively according to a prescheduled order. Under this mechanism, only one node is active at a time, while the other nodes are sleeping. The node whose turn is next wakes up according to one of three wakeup techniques: location-based, time-based and interrupt-driven. In this paper, mathematical models are derived for each technique to estimate the corresponding energy consumption and memory size requirements. The proposed equations are analyzed and the results are validated using simulation.

  12. Emerging therapies in pipeline for chronic hepatitis C

    Directory of Open Access Journals (Sweden)

    Navjot Kaur

    2013-10-01

    Full Text Available Hepatitis C infection represents a major global public health problem; as it leads to significant morbidity, mortality, and financial burden on healthcare system. According to world health organization, nearly 2- 3% (130-170 million of the world’s population has been infected with hepatitis C. The current standard therapy is limited both in efficacy and tolerability which highlights the large unmet medical need in this area. Recent advances in the understanding of lifecycle of hepatitis C virus and host cell interactions have led to the identification of multiple novel antiviral targets. Intense research effort is currently being directed towards translating these targets into developing more efficacious and safe treatment options for patients living with HCV infection. Current review aims to discuss the emerging therapies in pipeline for chronic hepatitis C outlining their mode of action and current stage of development in clinical trials. [Int J Basic Clin Pharmacol 2013; 2(5.000: 500-506

  13. Cell-specific activation and detoxification of benzene metabolites in mouse and human bone marrow: Identification of target cells and a potential role for modulation of apoptosis in benzene toxicity

    Energy Technology Data Exchange (ETDEWEB)

    Ross, D.; Siegel, D.; Schattenberg, D.G. [Univ. of Colorado Health Sciences Center, Denver, CO (United States)] [and others

    1996-12-01

    The role of cell-specific metabolism in benzene toxicity was examined in both murine and human bone marrow. Hemopoietic progenitor cells and stromal cells are important control points for regulation of hemopoiesis. We show that the selective toxicity of hydroquinone at the level of the macrophage in murine bone marrow stroma may be explained by a high peroxidase/nicotanimicle adenine dinucleotide phosphate, reduced [NAD(P)H]:quinone oxidoreductase (NQO1) ratio. Peroxidases metabolize hydroquinone to the reactive 1,4-benzoquinone, whereas NQO1 reduces the quinones formed, resulting in detoxification. Peroxidase and NQO1 activity in human stromal cultures vary as a function of time in culture, with peroxidase activity decreasing and NQO1 activity increasing with time. Peroxidase activity and, more specifically, myeloperoxidase, which had previously been considered to be expressed at the promyelocyte level, was detected in murine lineage-negative and human CD34{sup +} progenitor cells. This provides a metabolic mechanism whereby phenolic metabolites of benzene can be bioactivated in progenitor cells, which are considered initial target cells for the development of leukemias. Consequences of a high peroxidase/NQO1 ratio in HL-60 cells were shown to include hydroquinone-induced apoptosis. Hydroquinone can also inhibit proteases known to play a role in induction of apoptosis, suggesting that it may be able to inhibit apoptosis induced by other stimuli. Modulation of apoptosis may lead to aberrant hemopoiesis and neoplastic progression. This enzyme-directed approach has identified target cells of the phenolic metabolites of benzene in bone marrow and provided a metabolic basis for benzene-induced toxicity at the level of the progenitor cell in both murine and human bone marrow. 60 refs., 8 figs.

  14. Pipeline four-dimension management is the trend of pipeline integrity management in the future

    Energy Technology Data Exchange (ETDEWEB)

    Shaohua, Dong; Feifan; Zhongchen, Han [China National Petroleum Corporation (CNPC), Beijing (China)

    2009-07-01

    Pipeline integrity management is essential for today's operators to operate their pipelines safety and cost effectively. The latest developments of pipeline integrity management around the world are involved with change of regulation, industry standard and innovation of technology. And who know the trend of PIM in the future, which can be answered in the paper. As a result, the concept of P4DM was set up firstly in the world. The paper analyzed the pipeline HSE management, pipeline integrity management (PIM) and asset integrity management (AIM), the problem of management was produced, and also the Pipeline 4-dimension Management (P4DM) theory was brought forward. According to P4DM, from the hierarchy of P4DM, the management elements, fields, space and time was analyzed. The main content is P4DM integrate the space geography location and time, control and manage the pipeline system in whole process, anywhere and anytime. It includes the pipeline integrity, pipeline operation and emergency, which is integrated by IT system. It come true that the idea, solution, technology, organization, manager alternately intelligently control the process of management. What the paper talks about included the definition of pipeline 4D management, the research develop of P4DM, the theory of P4DM, the relationship between P4DM and PIM, the technology basis of P4DM, how to perform the P4DM and conclusion. The P4DM was produced, which provide the development direction of PIM in the future, and also provide the new ideas for PetroChina in the field of technology and management. (author)

  15. ProteoCloud: a full-featured open source proteomics cloud computing pipeline.

    Science.gov (United States)

    Muth, Thilo; Peters, Julian; Blackburn, Jonathan; Rapp, Erdmann; Martens, Lennart

    2013-08-02

    We here present the ProteoCloud pipeline, a freely available, full-featured cloud-based platform to perform computationally intensive, exhaustive searches in a cloud environment using five different peptide identification algorithms. ProteoCloud is entirely open source, and is built around an easy to use and cross-platform software client with a rich graphical user interface. This client allows full control of the number of cloud instances to initiate and of the spectra to assign for identification. It also enables the user to track progress, and to visualize and interpret the results in detail. Source code, binaries and documentation are all available at http://proteocloud.googlecode.com.

  16. PHOTOMETRYPIPELINE - An Automated Pipeline for Calibrated Photometry

    Science.gov (United States)

    Mommert, Michael; Moskovitz, Nicholas; Trilling, David E.

    2016-10-01

    Telescopes acquire massive amounts of imaging data every night. The goal of a large fraction of these observations is to obtain calibrated photometry for point sources - stars or moving Solar System targets - in different filters.We present PHOTOMETRYPIPELINE (PP, github.com/mommermi/photometrypipeline), an automated pipeline to obtain calibrated photometry from imaging data. PP is an open-source Python 2.7 software suite that provides image registration, aperture photometry, photometric calibration, and target identification with only minimal human interaction. For image registration, PP utilizes Source Extractor (Bertin & Arnouts 1996, A&AS, 117) and SWARP (Bertin et al. 2002, ASP Conf. S., 228) to find a plate solution for each frame, providing accurate target astrometry. Circular aperture photometry is performed using Source Extractor; an optimum aperture radius is identified using a curve-of-growth analysis. Photometric calibration is obtained through matching the background source catalog with star catalogs with reliable photometry (e.g., SDSS, URAT-1) in an iterative process; magnitude zeropoint accuracies are usually of the order of 0.03 mag, or better. Final calibrated photometry for each field source is written into a queriable database; target photometry is extracted from this database. Moving targets are identified using JPL Horizons (Giorgini et al. 1996, BAAS, 28) ephemerides. Image combination capabilities (using SWARP, Bertin 2006, ASP Conf. S., 112) are also available to improve the target's signal.PP is well-suited for data covering a few square arcminutes of the sky due to its dependence on background sources for registration and calibration. PP can be run on Unix-based systems on a simple desktop machine and is capable of realtime data analysis. PP has been developed for observations of moving targets, but can also be used on other observations. Efforts to improve the sky coverage for phometric calibration are in progress. Also, a module will be

  17. Validation of pig operations through pipelines

    Energy Technology Data Exchange (ETDEWEB)

    Tolmasquim, Sueli Tiomno [TRANSPETRO - PETROBRAS Transporte S.A., Rio de Janeiro, RJ (Brazil); Nieckele, Angela O. [Pontificia Univ. Catolica do Rio de Janeiro, RJ (Brazil). Dept. de Engenharia Mecanica

    2005-07-01

    In the oil industry, pigging operations in pipelines have been largely applied for different purposes: pipe cleaning, inspection, liquid removal and product separation, among others. An efficient and safe pigging operation requires that a number of operational parameters, such as maximum and minimum pressures in the pipeline and pig velocity, to be well evaluated during the planning stage and maintained within stipulated limits while the operation is accomplished. With the objective of providing an efficient tool to assist in the control and design of pig operations through pipelines, a numerical code was developed, based on a finite difference scheme, which allows the simulation of two fluid transient flow, like liquid-liquid, gas-gas or liquid-gas products in the pipeline. Modules to automatically control process variables were included to employ different strategies to reach an efficient operation. Different test cases were investigated, to corroborate the robustness of the methodology. To validate the methodology, the results obtained with the code were compared with a real liquid displacement operation of a section of the OSPAR oil pipeline, belonging to PETROBRAS, with 30'' diameter and 60 km length, presenting good agreement. (author)

  18. Bauxite slurry pipeline: start up operation

    Energy Technology Data Exchange (ETDEWEB)

    Othon, Otilio; Babosa, Eder; Edvan, Francisco; Brittes, Geraldo; Melo, Gerson; Janir, Joao; Favacho, Orlando; Leao, Marcos; Farias, Obadias [Vale, Rio de Janeiro, RJ (Brazil); Goncalves, Nilton [Anglo Ferrous Brazil S.A., Rio de Janeiro, RJ (Brazil)

    2009-07-01

    The mine of Miltonia is located in Paragominas-PA, in the north of Brazil. Bauxite slurry pipeline starts at the Mine of Miltonia and finishes in the draining installation of Alunorte refinery at the port of Barcarena-PA, located approximately 244km away from the mine. The pipeline runs over seven cities and passes below four great rivers stream beds. The system was designed for an underground 24 inches OD steel pipe to carry 9.9 million dry metric tonnes per annum (dMTAs) of 50.5% solid concentration bauxite slurry, using only one pumping station. The system is composed by four storage tanks and six piston diaphragm pumps, supplying a flow of 1680 m3/h. There is a cathodic protection system along the pipeline extension to prevent external corrosion and five pressure monitoring stations to control hydraulic conditions, there is also a fiber optic cable interconnection between pump station and terminal station. Pipeline Systems Incorporated (PSI) was the designer and followed the commissioning program of the start up operations. This paper will describe the beginning of the pipeline operations, technical aspects of the project, the operational experiences acquired in these two years, the faced problems and also the future planning. (author)

  19. Fiber optic accelerometer for pipeline surveillance

    Energy Technology Data Exchange (ETDEWEB)

    Valente, Luiz C.G.; Cabral, Bruno S. [LUPATECH Monitoring Systems, Caxias do Sul, RS (Brazil); Braga, Arthur M.B. [Pontificia Universidade Catolica do Rio de Janeiro (PUC-Rio), Rio de Janeiro, RJ (Brazil). Dept. de Engenharia Mecanica

    2009-07-01

    The use of accelerometers for monitoring vibration due to impacts and other sources associated with pipeline operation is not new, but conventional electric accelerometers present practical problems to be deployed in the field. In this paper we evaluate the use of both commercially available and prototypes of new optical fiber accelerometers for this application. They all share the possibility of operating at long distances from the reading unit. All tests were performed at CTDUT facilities on free pipes as well as on a 14 pol-OD, 100 meters long pipeline loop. Using controlled impacts, several aspects of the application have been analyzed such as different ways of fixing the accelerometers to the pipeline wall, influence of barriers between impact and sensor, and signal propagation through buried sections of pipeline. Results of measurements performed during the operation of the loop are also presented. They include passing PIGs, pumping water out from the system, and working on the tubes to open the loop. Results indicate that the accelerometers can be placed at distances measuring hundreds of meters from the source of vibration, and that the difference in time and frequency behavior of signals measured by sensors placed in different locations along the pipeline may be used to locate and identify that source. (author)

  20. JGI Plant Genomics Gene Annotation Pipeline

    Energy Technology Data Exchange (ETDEWEB)

    Shu, Shengqiang; Rokhsar, Dan; Goodstein, David; Hayes, David; Mitros, Therese

    2014-07-14

    Plant genomes vary in size and are highly complex with a high amount of repeats, genome duplication and tandem duplication. Gene encodes a wealth of information useful in studying organism and it is critical to have high quality and stable gene annotation. Thanks to advancement of sequencing technology, many plant species genomes have been sequenced and transcriptomes are also sequenced. To use these vastly large amounts of sequence data to make gene annotation or re-annotation in a timely fashion, an automatic pipeline is needed. JGI plant genomics gene annotation pipeline, called integrated gene call (IGC), is our effort toward this aim with aid of a RNA-seq transcriptome assembly pipeline. It utilizes several gene predictors based on homolog peptides and transcript ORFs. See Methods for detail. Here we present genome annotation of JGI flagship green plants produced by this pipeline plus Arabidopsis and rice except for chlamy which is done by a third party. The genome annotations of these species and others are used in our gene family build pipeline and accessible via JGI Phytozome portal whose URL and front page snapshot are shown below.