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Sample records for selected reaction monitoring

  1. Selected Reaction Monitoring Mass Spectrometry for Absolute Protein Quantification.

    PubMed

    Manes, Nathan P; Mann, Jessica M; Nita-Lazar, Aleksandra

    2015-01-01

    Absolute quantification of target proteins within complex biological samples is critical to a wide range of research and clinical applications. This protocol provides step-by-step instructions for the development and application of quantitative assays using selected reaction monitoring (SRM) mass spectrometry (MS). First, likely quantotypic target peptides are identified based on numerous criteria. This includes identifying proteotypic peptides, avoiding sites of posttranslational modification, and analyzing the uniqueness of the target peptide to the target protein. Next, crude external peptide standards are synthesized and used to develop SRM assays, and the resulting assays are used to perform qualitative analyses of the biological samples. Finally, purified, quantified, heavy isotope labeled internal peptide standards are prepared and used to perform isotope dilution series SRM assays. Analysis of all of the resulting MS data is presented. This protocol was used to accurately assay the absolute abundance of proteins of the chemotaxis signaling pathway within RAW 264.7 cells (a mouse monocyte/macrophage cell line). The quantification of Gi2 (a heterotrimeric G-protein α-subunit) is described in detail. PMID:26325288

  2. Protein Significance Analysis in Selected Reaction Monitoring (SRM) Measurements*

    PubMed Central

    Chang, Ching-Yun; Picotti, Paola; Hüttenhain, Ruth; Heinzelmann-Schwarz, Viola; Jovanovic, Marko; Aebersold, Ruedi; Vitek, Olga

    2012-01-01

    Selected reaction monitoring (SRM) is a targeted mass spectrometry technique that provides sensitive and accurate protein detection and quantification in complex biological mixtures. Statistical and computational tools are essential for the design and analysis of SRM experiments, particularly in studies with large sample throughput. Currently, most such tools focus on the selection of optimized transitions and on processing signals from SRM assays. Little attention is devoted to protein significance analysis, which combines the quantitative measurements for a protein across isotopic labels, peptides, charge states, transitions, samples, and conditions, and detects proteins that change in abundance between conditions while controlling the false discovery rate. We propose a statistical modeling framework for protein significance analysis. It is based on linear mixed-effects models and is applicable to most experimental designs for both isotope label-based and label-free SRM workflows. We illustrate the utility of the framework in two studies: one with a group comparison experimental design and the other with a time course experimental design. We further verify the accuracy of the framework in two controlled data sets, one from the NCI-CPTAC reproducibility investigation and the other from an in-house spike-in study. The proposed framework is sensitive and specific, produces accurate results in broad experimental circumstances, and helps to optimally design future SRM experiments. The statistical framework is implemented in an open-source R-based software package SRMstats, and can be used by researchers with a limited statistics background as a stand-alone tool or in integration with the existing computational pipelines. PMID:22190732

  3. Monitoring PPARG-Induced Changes in Glycolysis by Selected Reaction Monitoring Mass Spectrometry.

    PubMed

    Hentschel, Andreas; Ahrends, Robert

    2016-01-01

    As cells develop and differentiate, they change in function and morphology, which often precede earlier changes in signaling and metabolic control. Here we present a selected reaction monitoring (SRM) approach which allows for the parallel quantification of metabolic regulators and their downstream targets.In particular we explain and describe how to monitor abundance changes of glycolytic enzymes upon PPARγ activation by using a label-free or a stable isotope-labeled standard peptide (SIS peptides) approach applying triple-quadrupole mass spectrometry. We further outline how to fractionate the cell lysate into cytosolic and nuclear fractions to enhance the sensitivity of the measurements and to investigate the dynamic concentration changes in those compartments. PMID:26700041

  4. Photo-SRM: laser-induced dissociation improves detection selectivity of Selected Reaction Monitoring mode.

    PubMed

    Enjalbert, Quentin; Simon, Romain; Salvador, Arnaud; Antoine, Rodolphe; Redon, Sébastien; Ayhan, Mehmet Menaf; Darbour, Florence; Chambert, Stéphane; Bretonnière, Yann; Dugourd, Philippe; Lemoine, Jérôme

    2011-11-30

    Selected Reaction Monitoring (SRM) carried out on triple-quadrupole mass spectrometers coupled to liquid chromatography has been a reference method to develop quantitative analysis of small molecules in biological or environmental matrices for years and is currently emerging as a promising tool in clinical proteomic. However, sensitive assays in complex matrices are often hampered by the presence of co-eluted compounds that share redundant transitions with the target species. On-the-fly better selection of the precursor ion by high-field asymmetric waveform ion mobility spectrometry (FAIMS) or increased quadrupole resolution is one way to escape from interferences. In the present work we document the potential interest of substituting classical gas-collision activation mode by laser-induced dissociation in the visible wavelength range to improve the specificity of the fragmentation step. Optimization of the laser beam pathway across the different quadrupoles to ensure high photo-dissociation yield in Q2 without detectable fragmentation in Q1 was assessed with sucrose tagged with a push-pull chromophore. Next, the proof of concept that photo-SRM ensures more specific detection than does conventional collision-induced dissociation (CID)-based SRM was carried out with oxytocin peptide. Oxytocin was derivatized by the thiol-reactive QSY® 7 C(5)-maleimide quencher on cysteine residues to shift its absorption property into the visible range. Photo-SRM chromatograms of tagged oxytocin spiked in whole human plasma digest showed better detection specificity and sensitivity than CID, that resulted in extended calibration curve linearity. We anticipate that photo-SRM might significantly improve the limit of quantification of classical SRM-based assays targeting cysteine-containing peptides. PMID:22002689

  5. Rapid Bacterial Identification, Resistance, Virulence and Type Profiling using Selected Reaction Monitoring Mass Spectrometry.

    PubMed

    Charretier, Yannick; Dauwalder, Olivier; Franceschi, Christine; Degout-Charmette, Elodie; Zambardi, Gilles; Cecchini, Tiphaine; Bardet, Chloe; Lacoux, Xavier; Dufour, Philippe; Veron, Laurent; Rostaing, Hervé; Lanet, Veronique; Fortin, Tanguy; Beaulieu, Corinne; Perrot, Nadine; Dechaume, Dominique; Pons, Sylvie; Girard, Victoria; Salvador, Arnaud; Durand, Géraldine; Mallard, Frédéric; Theretz, Alain; Broyer, Patrick; Chatellier, Sonia; Gervasi, Gaspard; Van Nuenen, Marc; Roitsch, Carolyn Ann; Van Belkum, Alex; Lemoine, Jérôme; Vandenesch, François; Charrier, Jean-Philippe

    2015-01-01

    Mass spectrometry (MS) in Selected Reaction Monitoring (SRM) mode is proposed for in-depth characterisation of microorganisms in a multiplexed analysis. Within 60-80 minutes, the SRM method performs microbial identification (I), antibiotic-resistance detection (R), virulence assessment (V) and it provides epidemiological typing information (T). This SRM application is illustrated by the analysis of the human pathogen Staphylococcus aureus, demonstrating its promise for rapid characterisation of bacteria from positive blood cultures of sepsis patients. PMID:26350205

  6. Rapid Bacterial Identification, Resistance, Virulence and Type Profiling using Selected Reaction Monitoring Mass Spectrometry

    PubMed Central

    Charretier, Yannick; Dauwalder, Olivier; Franceschi, Christine; Degout-Charmette, Elodie; Zambardi, Gilles; Cecchini, Tiphaine; Bardet, Chloe; Lacoux, Xavier; Dufour, Philippe; Veron, Laurent; Rostaing, Hervé; Lanet, Veronique; Fortin, Tanguy; Beaulieu, Corinne; Perrot, Nadine; Dechaume, Dominique; Pons, Sylvie; Girard, Victoria; Salvador, Arnaud; Durand, Géraldine; Mallard, Frédéric; Theretz, Alain; Broyer, Patrick; Chatellier, Sonia; Gervasi, Gaspard; Van Nuenen, Marc; Ann Roitsch, Carolyn; Van Belkum, Alex; Lemoine, Jérôme; Vandenesch, François; Charrier, Jean-Philippe

    2015-01-01

    Mass spectrometry (MS) in Selected Reaction Monitoring (SRM) mode is proposed for in-depth characterisation of microorganisms in a multiplexed analysis. Within 60–80 minutes, the SRM method performs microbial identification (I), antibiotic-resistance detection (R), virulence assessment (V) and it provides epidemiological typing information (T). This SRM application is illustrated by the analysis of the human pathogen Staphylococcus aureus, demonstrating its promise for rapid characterisation of bacteria from positive blood cultures of sepsis patients. PMID:26350205

  7. Targeted Phosphoproteome Analysis Using Selected/Multiple Reaction Monitoring (SRM/MRM).

    PubMed

    Adachi, Jun; Narumi, Ryohei; Tomonaga, Takeshi

    2016-01-01

    Mass spectrometry-based phosphoproteomics has been rapidly spread based on the advancement of mass spectrometry and development of efficient enrichment techniques for phosphorylated proteins or peptides. Non-targeted approach has been employed in most of the studies for phosphoproteome analysis. However, targeted approach using selected/multiple reaction monitoring (SRM/MRM) is an indispensible technique used for the quantitation of known targets especially when we have many samples to quantitate phosphorylation events on proteins in biological or clinical samples. We herein describe the application of a large-scale phosphoproteome analysis and SRM-based quantitation for the systematic discovery and validation of biomarkers. PMID:26700043

  8. Direct and Absolute Quantification of over 1800 Yeast Proteins via Selected Reaction Monitoring*

    PubMed Central

    Lawless, Craig; Holman, Stephen W.; Brownridge, Philip; Lanthaler, Karin; Harman, Victoria M.; Watkins, Rachel; Hammond, Dean E.; Miller, Rebecca L.; Sims, Paul F. G.; Grant, Christopher M.; Eyers, Claire E.; Beynon, Robert J.

    2016-01-01

    Defining intracellular protein concentration is critical in molecular systems biology. Although strategies for determining relative protein changes are available, defining robust absolute values in copies per cell has proven significantly more challenging. Here we present a reference data set quantifying over 1800 Saccharomyces cerevisiae proteins by direct means using protein-specific stable-isotope labeled internal standards and selected reaction monitoring (SRM) mass spectrometry, far exceeding any previous study. This was achieved by careful design of over 100 QconCAT recombinant proteins as standards, defining 1167 proteins in terms of copies per cell and upper limits on a further 668, with robust CVs routinely less than 20%. The selected reaction monitoring-derived proteome is compared with existing quantitative data sets, highlighting the disparities between methodologies. Coupled with a quantification of the transcriptome by RNA-seq taken from the same cells, these data support revised estimates of several fundamental molecular parameters: a total protein count of ∼100 million molecules-per-cell, a median of ∼1000 proteins-per-transcript, and a linear model of protein translation explaining 70% of the variance in translation rate. This work contributes a “gold-standard” reference yeast proteome (including 532 values based on high quality, dual peptide quantification) that can be widely used in systems models and for other comparative studies. PMID:26750110

  9. Direct and Absolute Quantification of over 1800 Yeast Proteins via Selected Reaction Monitoring.

    PubMed

    Lawless, Craig; Holman, Stephen W; Brownridge, Philip; Lanthaler, Karin; Harman, Victoria M; Watkins, Rachel; Hammond, Dean E; Miller, Rebecca L; Sims, Paul F G; Grant, Christopher M; Eyers, Claire E; Beynon, Robert J; Hubbard, Simon J

    2016-04-01

    Defining intracellular protein concentration is critical in molecular systems biology. Although strategies for determining relative protein changes are available, defining robust absolute values in copies per cell has proven significantly more challenging. Here we present a reference data set quantifying over 1800Saccharomyces cerevisiaeproteins by direct means using protein-specific stable-isotope labeled internal standards and selected reaction monitoring (SRM) mass spectrometry, far exceeding any previous study. This was achieved by careful design of over 100 QconCAT recombinant proteins as standards, defining 1167 proteins in terms of copies per cell and upper limits on a further 668, with robust CVs routinely less than 20%. The selected reaction monitoring-derived proteome is compared with existing quantitative data sets, highlighting the disparities between methodologies. Coupled with a quantification of the transcriptome by RNA-seq taken from the same cells, these data support revised estimates of several fundamental molecular parameters: a total protein count of ∼100 million molecules-per-cell, a median of ∼1000 proteins-per-transcript, and a linear model of protein translation explaining 70% of the variance in translation rate. This work contributes a "gold-standard" reference yeast proteome (including 532 values based on high quality, dual peptide quantification) that can be widely used in systems models and for other comparative studies. PMID:26750110

  10. Advancing the sensitivity of selected reaction monitoring-based targeted quantitative proteomics

    SciTech Connect

    Shi, Tujin; Su, Dian; Liu, Tao; Tang, Keqi; Camp, David G.; Qian, Weijun; Smith, Richard D.

    2012-04-01

    Selected reaction monitoring (SRM)—also known as multiple reaction monitoring (MRM)—has emerged as a promising high-throughput targeted protein quantification technology for candidate biomarker verification and systems biology applications. A major bottleneck for current SRM technology, however, is insufficient sensitivity for e.g., detecting low-abundance biomarkers likely present at the pg/mL to low ng/mL range in human blood plasma or serum, or extremely low-abundance signaling proteins in the cells or tissues. Herein we review recent advances in methods and technologies, including front-end immunoaffinity depletion, fractionation, selective enrichment of target proteins/peptides or their posttranslational modifications (PTMs), as well as advances in MS instrumentation, which have significantly enhanced the overall sensitivity of SRM assays and enabled the detection of low-abundance proteins at low to sub- ng/mL level in human blood plasma or serum. General perspectives on the potential of achieving sufficient sensitivity for detection of pg/mL level proteins in plasma are also discussed.

  11. Protein quantification by MALDI-selected reaction monitoring mass spectrometry using sulfonate derivatized peptides.

    PubMed

    Lesur, Antoine; Varesio, Emmanuel; Hopfgartner, Gérard

    2010-06-15

    The feasibility of protein absolute quantification with matrix-assisted laser desorption/ionization (MALDI) using the selected reaction monitoring (SRM) acquisition mode on a triple quadrupole linear ion trap mass spectrometer (QqQ(LIT)) equipped with a high-frequency laser is demonstrated. A therapeutic human monoclonal antibody (mAb) was used as a model protein, and four tryptic peptides generated by fast tryptic digestion were selected as quantification surrogates. MALDI produces mostly singly charged peptides which hardly fragment under low-energy collision-induced dissociation (CID), and therefore the benefits of using 4-sulfophenyl isothiocyanate (SPITC) as a fragmentation enhancer derivatization agent were evaluated. Despite a moderate impact on the sensitivity, the N-terminus sulfonated peptides generate nearly complete y-ion ladders when native peptides produce few fragments. This aspect provides an alternative SRM transition set for each peptide. As a consequence, SRM transitions selectivity can be tuned more easily for peptide quantitation in complex matrices when monitoring several SRM transitions. From a quantitative point of view, the signal response depending on mAb concentration was found to be linear over 2.5 orders of magnitude for the most sensitive peptide, allowing precise and accurate measurement by MALDI-SRM/MS. PMID:20481516

  12. Ultrasensitive Sample Quantitation via Selected Reaction Monitoring Using CITP/CZE-ESI-Triple Quadrupole MS

    PubMed Central

    Wang, Chenchen; Lee, Cheng S.; Smith, Richard D.; Tang, Keqi

    2013-01-01

    We demonstrate the direct coupling of transient capillary isotachophoresis/ capillary zone electrophoresis (CITP/CZE) with a high sensitivity triple quadrupole mass spectrometer operating in selected reaction monitoring (SRM) mode for sample quantitation. The capability of CITP/CZE for in situ sample enrichment and separation has been shown to significantly improve the analytical figures of merit. A linear dynamic range spanning 4 orders of magnitude was observed. An average signal-to-noise ratio (S/N) of 49.6 was observed for 50 attomoles of targeted peptide in the presence of a complex and much more abundant bovine serum albumin (BSA) digest product. A correlation of variation (CV) less than 10 % for peak area was measured from triplicate sample analyses at 50 pM peptide concentration, showing good reproducibility of this online CITP/CZE-SRM mass spectrometry (MS) platform, and with limit of quantitation (LOQ) demonstrated to be well below 50 pM. PMID:23140208

  13. Ultrasensitive Sample Quantitation via Selected Reaction Monitoring Using CITP/CZE-ESI-Triple Quadrupole MS

    SciTech Connect

    Wang, Chenchen; Lee, Cheng S.; Smith, Richard D.; Tang, Keqi

    2012-11-10

    We demonstrate the direct coupling of transient capillary isotachophoresis/ capillary zone electrophoresis (CITP/CZE) with a high sensitivity triple quadrupole mass spectrometer operating in selected reaction monitoring (SRM) mode for sample quantitation. The capability of CITP/CZE for in situ sample enrichment and separation has been shown to significantly improve the analytical figures of merit. A linear dynamic range spanning more than 4 orders of magnitude was observed. An average signal-to-noise ratio (S/N) of 49.6 was observed for 50 attomoles of targeted peptide in the presence of a complex and much more abundant bovine serum albumin (BSA) digest products. A correlation of variation (CV) less than 10 % for peak area was measured from triplicate sample analyses at 50 pM peptide concentration, showing good reproducibility of this online CITP/CZE-SRM mass spectrometry (MS) platform, and with limit of quantitation (LOQ) demonstrated to be well below 50 pM.

  14. Estimation of absolute protein quantities of unlabeled samples by selected reaction monitoring mass spectrometry.

    PubMed

    Ludwig, Christina; Claassen, Manfred; Schmidt, Alexander; Aebersold, Ruedi

    2012-03-01

    For many research questions in modern molecular and systems biology, information about absolute protein quantities is imperative. This information includes, for example, kinetic modeling of processes, protein turnover determinations, stoichiometric investigations of protein complexes, or quantitative comparisons of different proteins within one sample or across samples. To date, the vast majority of proteomic studies are limited to providing relative quantitative comparisons of protein levels between limited numbers of samples. Here we describe and demonstrate the utility of a targeting MS technique for the estimation of absolute protein abundance in unlabeled and nonfractionated cell lysates. The method is based on selected reaction monitoring (SRM) mass spectrometry and the "best flyer" hypothesis, which assumes that the specific MS signal intensity of the most intense tryptic peptides per protein is approximately constant throughout a whole proteome. SRM-targeted best flyer peptides were selected for each protein from the peptide precursor ion signal intensities from directed MS data. The most intense transitions per peptide were selected from full MS/MS scans of crude synthetic analogs. We used Monte Carlo cross-validation to systematically investigate the accuracy of the technique as a function of the number of measured best flyer peptides and the number of SRM transitions per peptide. We found that a linear model based on the two most intense transitions of the three best flying peptides per proteins (TopPep3/TopTra2) generated optimal results with a cross-correlated mean fold error of 1.8 and a squared Pearson coefficient R(2) of 0.88. Applying the optimized model to lysates of the microbe Leptospira interrogans, we detected significant protein abundance changes of 39 target proteins upon antibiotic treatment, which correlate well with literature values. The described method is generally applicable and exploits the inherent performance advantages of SRM

  15. Automated Selected Reaction Monitoring Software for Accurate Label-Free Protein Quantification

    PubMed Central

    2012-01-01

    Selected reaction monitoring (SRM) is a mass spectrometry method with documented ability to quantify proteins accurately and reproducibly using labeled reference peptides. However, the use of labeled reference peptides becomes impractical if large numbers of peptides are targeted and when high flexibility is desired when selecting peptides. We have developed a label-free quantitative SRM workflow that relies on a new automated algorithm, Anubis, for accurate peak detection. Anubis efficiently removes interfering signals from contaminating peptides to estimate the true signal of the targeted peptides. We evaluated the algorithm on a published multisite data set and achieved results in line with manual data analysis. In complex peptide mixtures from whole proteome digests of Streptococcus pyogenes we achieved a technical variability across the entire proteome abundance range of 6.5–19.2%, which was considerably below the total variation across biological samples. Our results show that the label-free SRM workflow with automated data analysis is feasible for large-scale biological studies, opening up new possibilities for quantitative proteomics and systems biology. PMID:22658081

  16. Selective monitoring

    NASA Astrophysics Data System (ADS)

    Homem-de-Mello, Luiz S.

    1992-04-01

    While in NASA's earlier space missions such as Voyager the number of sensors was in the hundreds, future platforms such as the Space Station Freedom will have tens of thousands sensors. For these planned missions it will be impossible to use the comprehensive monitoring strategy that was used in the past in which human operators monitored all sensors all the time. A selective monitoring strategy must be substituted for the current comprehensive strategy. This selective monitoring strategy uses computer tools to preprocess the incoming data and direct the operators' attention to the most critical parts of the physical system at any given time. There are several techniques that can be used to preprocess the incoming information. This paper presents an approach to using diagnostic reasoning techniques to preprocess the sensor data and detect which parts of the physical system require more attention because components have failed or are most likely to have failed. Given the sensor readings and a model of the physical system, a number of assertions are generated and expressed as Boolean equations. The resulting system of Boolean equations is solved symbolically. Using a priori probabilities of component failure and Bayes' rule, revised probabilities of failure can be computed. These will indicate what components have failed or are the most likely to have failed. This approach is suitable for systems that are well understood and for which the correctness of the assertions can be guaranteed. Also, the system must be such that assertions can be made from instantaneous measurements. And the system must be such that changes are slow enough to allow the computation.

  17. Targeted Selected Reaction Monitoring Mass Spectrometric Immunoassay for Insulin-like Growth Factor 1

    PubMed Central

    Niederkofler, Eric E.; Phillips, David A.; Krastins, Bryan; Kulasingam, Vathany; Kiernan, Urban A.; Tubbs, Kemmons A.; Peterman, Scott M.; Prakash, Amol; Diamandis, Eleftherios P.; Lopez, Mary F.; Nedelkov, Dobrin

    2013-01-01

    Insulin-like growth factor 1 (IGF1) is an important biomarker of human growth disorders that is routinely analyzed in clinical laboratories. Mass spectrometry-based workflows offer a viable alternative to standard IGF1 immunoassays, which utilize various pre-analytical preparation strategies. In this work we developed an assay that incorporates a novel sample preparation method for dissociating IGF1 from its binding proteins. The workflow also includes an immunoaffinity step using antibody-derivatized pipette tips, followed by elution, trypsin digestion, and LC-MS/MS separation and detection of the signature peptides in a selected reaction monitoring (SRM) mode. The resulting quantitative mass spectrometric immunoassay (MSIA) exhibited good linearity in the range of 1 to 1,500 ng/mL IGF1, intra- and inter-assay precision with CVs of less than 10%, and lowest limits of detection of 1 ng/mL. The linearity and recovery characteristics of the assay were also established, and the new method compared to a commercially available immunoassay using a large cohort of human serum samples. The IGF1 SRM MSIA is well suited for use in clinical laboratories. PMID:24278387

  18. Detection and quantification of plasma amyloid-β by selected reaction monitoring mass spectrometry.

    PubMed

    Kim, Jun Seok; Ahn, Hee-Sung; Cho, Soo Min; Lee, Ji Eun; Kim, YoungSoo; Lee, Cheolju

    2014-08-20

    Amyloid-β (Aβ) in human plasma was detected and quantified by an antibody-free method, selected reaction monitoring mass spectrometry (SRM-MS) in the current study. Due to its low abundance, SRM-based quantification in 10 μL plasma was a challenge. Prior to SRM analysis, human plasma proteins as a whole were digested by trypsin and high pH reversed-phase liquid chromatography (RPLC) was used to fractionate the tryptic digests and to collect peptides, Aβ(1-5), Aβ(6-16), Aβ(17-28) and Aβ(29-40(42)) of either Aβ(1-40) or Aβ(1-42). Among those peptides, Aβ(17-28) was selected as a surrogate to measure the total Aβ level. Human plasma samples obtained from triplicate sample preparations were analyzed, obtaining 4.20 ng mL(-1) with a CV of 25.3%. Triplicate measurements for each sample preparation showed CV of <5%. Limit of quantification was obtained as 132 pM, which corresponded to 570 pg mL(-1) of Aβ(1-40). Until now, most quantitative measurements of Aβ in plasma or cerebrospinal fluid have required antibody-based immunoassays. Since quantification of Aβ by immunoassays is highly dependent on the extent of epitope exposure due to aggregation or plasma protein binding, it is difficult to accurately measure the actual concentration of Aβ in plasma. Our diagnostic method based on SRM using a surrogate peptide of Aβ is promising in that actual amounts of total Aβ can be measured regardless of the conformational status of the biomarker. PMID:25086887

  19. Determination of alkanolamines in cattails (Typha latifolia) utilizing electrospray ionization with selected reaction monitoring and ion-exchange chromatography.

    PubMed

    Peru, Kerry M; Headley, John V; Doucette, William J

    2004-01-01

    Selected reaction monitoring (SRM) with electrospray ionization was used as a specific detection technique for the analysis of alkanolamines in plant tissue extracts. Ion-exchange chromatography was used as the method of separation. Quantification was based on monitoring the loss of either H2O or 2(H2O) from the protonated molecule [M+H]+. The method provided increased selectivity for all analytes and better detection limits for three of the six analytes investigated compared with an earlier method using selected ion monitoring with liquid chromatography. Instrumental detection limits ranged from 6-300 pg injected for monoethanolamine (MEA), monoisopropanolamine (MIPA), diethanolamine (DEA), methyldiethanolamine (MDEA), diisopropanolamine (DIPA), and triethanolamine (TEA). Method robustness and selectivity were demonstrated by the determination of DIPA and a known transformation product MIPA in over 35 plant extract samples derived from a laboratory study of plant uptake mechanisms. PMID:15282789

  20. Development of Mass Spectrometry Selected Reaction Monitoring Method for Quantitation and Pharmacokinetic Study of Stepharine in Rabbit Plasma

    PubMed Central

    Kopylov, Arthur T.; Kuznetsova, Ksenia G.; Mikhailova, Olga M.; Moshkin, Andrey G.; Turkin, Vladimir V.; Alimov, Andrei A.

    2014-01-01

    Highly sensitive liquid chromatography mass spectrometry method on triple quadrupole (QQQ) mass spectrometer was successfully applied for pharmacokinetic study of stepharine in rabbit plasma. Specific ion transitions of stepharine protonated precursor ion were selected and recorded in the certain retention time employing dynamic selected reaction monitoring mode. The developed method facilitated quantitative measurements of stepharine in plasma samples in linear range of five orders of magnitude with high accuracy and low standard deviation coefficient and pharmacokinetics parameters were calculated. The apparent volume of stepharine distribution (estimated as ratio of clearance to elimination rate constant, data not shown) allows us to assume that stepharine was extensively distributed throughout the body. PMID:24696679

  1. Targeted Multiplexed Selected Reaction Monitoring Analysis Evaluates Protein Expression Changes of Molecular Risk Factors for Major Psychiatric Disorders

    PubMed Central

    Wesseling, Hendrik; Gottschalk, Michael G.

    2015-01-01

    Background: Extensive research efforts have generated genomic, transcriptomic, proteomic, and functional data hoping to elucidate psychiatric pathophysiology. Selected reaction monitoring, a recently developed targeted proteomic mass spectrometric approach, has made it possible to evaluate previous findings and hypotheses with high sensitivity, reproducibility, and quantitative accuracy. Methods: Here, we have developed a labelled multiplexed selected reaction monitoring assay, comprising 56 proteins previously implicated in the aetiology of major psychiatric disorders, including cell type markers or targets and effectors of known psychopharmacological interventions. We analyzed postmortem anterior prefrontal cortex (Brodmann area 10) tissue of patients diagnosed with schizophrenia (n=22), bipolar disorder (n=23), and major depressive disorder with (n=11) and without (n=11) psychotic features compared with healthy controls (n=22). Results: Results agreed with several previous studies, with the finding of alterations of Wnt-signalling and glutamate receptor abundance predominately in bipolar disorder and abnormalities in energy metabolism across the neuropsychiatric disease spectrum. Calcium signalling was predominantly affected in schizophrenia and affective psychosis. Interestingly, we were able to show a decrease of all 4 tested oligodendrocyte specific proteins (MOG, MBP, MYPR, CNPase) in bipolar disorder and to a lesser extent in schizophrenia and affective psychosis. Finally, we provide new evidence linking ankyrin 3 specifically to affective psychosis and the 22q11.2 deletion syndrome-associated protein septin 5 to schizophrenia. Conclusions: Our study highlights the potential of selected reaction monitoring to evaluate the protein abundance levels of candidate markers of neuropsychiatric spectrum disorders, providing a high throughput multiplex platform for validation of putative disease markers and drug targets. PMID:25539505

  2. ANALYSIS FOR B-LACTAM ANTIBIOTICS IN KIDNEY TISSUE BY LIQUID CHROMATOGRAPHY WITH ELECTROSPRAY IONIZATION AND SELECTIVE REACTION MONITORING/TANDEM ION TRAP MASS SPECTROMETRY

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Eleven B-lactams antibiotics were analyzed in fortified and incurred beef kidney tissue using high-performance liquid chromatography/selective reaction monitoring/tandem ion trap mass spectrometry. The analytes included: deacetylcephapirin, amoxicillin, cephapirin, desfuroylceftiofur cysteine disul...

  3. Diet-induced neuropeptide expression: feasibility of quantifying extended and highly charged endogenous peptide sequences by selected reaction monitoring.

    PubMed

    Schmidlin, Thierry; Boender, Arjen J; Frese, Christian K; Heck, Albert J R; Adan, Roger A H; Altelaar, A F Maarten

    2015-10-01

    Understanding regulation and action of endogenous peptides, especially neuropeptides, which serve as inter- and intracellular signal transmitters, is key in understanding a variety of functional processes, such as energy balance, memory, circadian rhythm, drug addiction, etc. Therefore, accurate and reproducible quantification of these bioactive endogenous compounds is highly relevant. The biosynthesis of endogenous peptides, involving multiple possible trimming and modification events, hinders the de novo prediction of the active peptide sequences, making MS-based measurements very valuable in determining the actual active compounds. Here, we report an extended selected reaction monitoring (SRM)-based strategy to reproducibly and quantitatively monitor the abundances of a set of 15 endogenously occurring peptides from Rattus norvegicus hypothalamus. We demonstrate that SRM can be extended toward reproducible detection and quantification of peptides, bearing characteristics very different from tryptic peptides. We show that long peptide sequences, producing precursors with up to five and MS2 fragment ions with up to three charges, can be targeted by SRM on a triple quadrupole instrument. Using this approach to quantify endogenous peptide levels in hypothalami of animals subjected to different diets revealed several significant changes, most notably the significant upregulation of VGF-derived signaling peptide AQEE-30 upon high caloric feeding. PMID:26376940

  4. Mass Spectrometric-Based Selected Reaction Monitoring of Protein Phosphorylation during Symbiotic Signaling in the Model Legume, Medicago truncatula

    PubMed Central

    Maeda, Junko; Barrett-Wilt, Gregory A.; Sussman, Michael R.

    2016-01-01

    Unlike the major cereal crops corn, rice, and wheat, leguminous plants such as soybean and alfalfa can meet their nitrogen requirement via endosymbiotic associations with soil bacteria. The establishment of this symbiosis is a complex process playing out over several weeks and is facilitated by the exchange of chemical signals between these partners from different kingdoms. Several plant components that are involved in this signaling pathway have been identified, but there is still a great deal of uncertainty regarding the early events in symbiotic signaling, i.e., within the first minutes and hours after the rhizobial signals (Nod factors) are perceived at the plant plasma membrane. The presence of several protein kinases in this pathway suggests a mechanism of signal transduction via posttranslational modification of proteins in which phosphate is added to the hydroxyl groups of serine, threonine and tyrosine amino acid side chains. To monitor the phosphorylation dynamics and complement our previous untargeted 'discovery' approach, we report here the results of experiments using a targeted mass spectrometric technique, Selected Reaction Monitoring (SRM) that enables the quantification of phosphorylation targets with great sensitivity and precision. Using this approach, we confirm a rapid change in the level of phosphorylation in 4 phosphosites of at least 4 plant phosphoproteins that have not been previously characterized. This detailed analysis reveals aspects of the symbiotic signaling mechanism in legumes that, in the long term, will inform efforts to engineer this nitrogen-fixing symbiosis in important non-legume crops such as rice, wheat and corn. PMID:27203723

  5. Mass Spectrometric-Based Selected Reaction Monitoring of Protein Phosphorylation during Symbiotic Signaling in the Model Legume, Medicago truncatula.

    PubMed

    Van Ness, Lori K; Jayaraman, Dhileepkumar; Maeda, Junko; Barrett-Wilt, Gregory A; Sussman, Michael R; Ané, Jean-Michel

    2016-01-01

    Unlike the major cereal crops corn, rice, and wheat, leguminous plants such as soybean and alfalfa can meet their nitrogen requirement via endosymbiotic associations with soil bacteria. The establishment of this symbiosis is a complex process playing out over several weeks and is facilitated by the exchange of chemical signals between these partners from different kingdoms. Several plant components that are involved in this signaling pathway have been identified, but there is still a great deal of uncertainty regarding the early events in symbiotic signaling, i.e., within the first minutes and hours after the rhizobial signals (Nod factors) are perceived at the plant plasma membrane. The presence of several protein kinases in this pathway suggests a mechanism of signal transduction via posttranslational modification of proteins in which phosphate is added to the hydroxyl groups of serine, threonine and tyrosine amino acid side chains. To monitor the phosphorylation dynamics and complement our previous untargeted 'discovery' approach, we report here the results of experiments using a targeted mass spectrometric technique, Selected Reaction Monitoring (SRM) that enables the quantification of phosphorylation targets with great sensitivity and precision. Using this approach, we confirm a rapid change in the level of phosphorylation in 4 phosphosites of at least 4 plant phosphoproteins that have not been previously characterized. This detailed analysis reveals aspects of the symbiotic signaling mechanism in legumes that, in the long term, will inform efforts to engineer this nitrogen-fixing symbiosis in important non-legume crops such as rice, wheat and corn. PMID:27203723

  6. Rapid determination of parabens in personal care products by stable isotope GC-MS/MS with dynamic selected reaction monitoring.

    PubMed

    Wang, Perry G; Zhou, Wanlong

    2013-06-01

    In this study, a rapid and sensitive analytical method for the determination of methyl-, ethyl-, propyl-, and butyl esters of para-hydroxy benzoic acid (parabens) in personal care products was developed and fully validated. Test portions were extracted with methanol followed by vortexing, sonication, centrifugation, and filtration without derivatization. The four parabens were quantified by GC-MS/MS in the electron ionization mode. Four corresponding isotopically labeled parabens were selected as internal standards, which were added at the beginning of the sample preparation and used to correct for recovery and matrix effects. Sensitivity, extraction efficiency, and recovery of the respective analytes were evaluated. The coefficients of determination (r(2)) were all greater than 0.995 for the four parabens investigated. The recoveries ranged from 97 to 107% at three spiked levels and a one-time (single) extraction efficiency greater than 97% was obtained. This method has been applied to screen 26 personal care products. This is the first time that a unique GC-MS/MS method with dynamic selected reaction monitoring and confirmation of analytes has been used to determine these parabens in cosmetic personal care products. PMID:23494853

  7. Selected reaction monitoring as an effective method for reliable quantification of disease-associated proteins in maple syrup urine disease.

    PubMed

    Fernández-Guerra, Paula; Birkler, Rune I D; Merinero, Begoña; Ugarte, Magdalena; Gregersen, Niels; Rodríguez-Pombo, Pilar; Bross, Peter; Palmfeldt, Johan

    2014-09-01

    Selected reaction monitoring (SRM) mass spectrometry can quantitatively measure proteins by specific targeting of peptide sequences, and allows the determination of multiple proteins in one single analysis. Here, we show the feasibility of simultaneous measurements of multiple proteins in mitochondria-enriched samples from cultured fibroblasts from healthy individuals and patients with mutations in branched-chain α-ketoacid dehydrogenase (BCKDH) complex. BCKDH is a mitochondrial multienzyme complex and its defective activity causes maple syrup urine disease (MSUD), a rare but severe inherited metabolic disorder. Four different genes encode the catalytic subunits of BCKDH: E1α (BCKDHA), E1β (BCKDHB), E2 (DBT), and E3 (DLD). All four proteins were successfully quantified in healthy individuals. However, the E1α and E1β proteins were not detected in patients carrying mutations in one of those genes, whereas mRNA levels were almost unaltered, indicating instability of E1α and E1β monomers. Using SRM we elucidated the protein effects of mutations generating premature termination codons or misfolded proteins. SRM is a complement to transcript level measurements and a valuable tool to shed light on molecular mechanisms and on effects of pharmacological therapies at protein level. SRM is particularly effective for inherited disorders caused by multiple proteins such as defects in multienzyme complexes. PMID:25333063

  8. Orthogonal Injection Ion Funnel Interface Providing Enhanced Performance for Selected Reaction Monitoring-Triple Quadrupole Mass Spectrometry

    DOE PAGESBeta

    Chen, Tsung-Chi; Fillmore, Thomas L.; Prost, Spencer A.; Moore, Ronald J.; Ibrahim, Yehia M.; Smith, Richard D.

    2015-06-24

    The electrodynamic ion funnel facilitates efficient focusing and transfer of charged particles in the higher pressure regions (e.g. ion source interfaces) of mass spectrometers, and thus providing increased sensitivity. An “off-axis” ion funnel design has been developed to reduce the source contamination and interferences from, e.g. ESI droplet residue and other poorly focused neutral or charged particles with very high mass-to charge ratios. In this study a dual ion funnel interface consisting of an orthogonal higher pressure electrodynamic ion funnel (HPIF) and an ion funnel trap combined with a triple quadruple mass spectrometer was developed and characterized. An orthogonal ionmore » injection inlet and a repeller plate electrode was used to direct ions to an ion funnel HPIF at 9-10 Torr pressure. Several critical factors for the HPIF were characterized, including the effects of RF amplitude, DC gradient and operating pressure. Compared to the triple quadrupole standard interface more than 4-fold improvement in the limit of detection for the direct quantitative MS analysis of low abundance peptides was observed. Lastly, the sensitivity enhancement in liquid chromatography selected reaction monitoring (SRM) analyses of low abundance peptides spiked into a highly complex mixture was also compared with that obtained using a both commercial s-lens interface and a in-line dual ion funnel interface.« less

  9. Orthogonal Injection Ion Funnel Interface Providing Enhanced Performance for Selected Reaction Monitoring-Triple Quadrupole Mass Spectrometry

    SciTech Connect

    Chen, Tsung-Chi; Fillmore, Thomas L.; Prost, Spencer A.; Moore, Ronald J.; Ibrahim, Yehia M.; Smith, Richard D.

    2015-06-24

    The electrodynamic ion funnel facilitates efficient focusing and transfer of charged particles in the higher pressure regions (e.g. ion source interfaces) of mass spectrometers, and thus providing increased sensitivity. An “off-axis” ion funnel design has been developed to reduce the source contamination and interferences from, e.g. ESI droplet residue and other poorly focused neutral or charged particles with very high mass-to charge ratios. In this study a dual ion funnel interface consisting of an orthogonal higher pressure electrodynamic ion funnel (HPIF) and an ion funnel trap combined with a triple quadruple mass spectrometer was developed and characterized. An orthogonal ion injection inlet and a repeller plate electrode was used to direct ions to an ion funnel HPIF at 9-10 Torr pressure. Several critical factors for the HPIF were characterized, including the effects of RF amplitude, DC gradient and operating pressure. Compared to the triple quadrupole standard interface more than 4-fold improvement in the limit of detection for the direct quantitative MS analysis of low abundance peptides was observed. Lastly, the sensitivity enhancement in liquid chromatography selected reaction monitoring (SRM) analyses of low abundance peptides spiked into a highly complex mixture was also compared with that obtained using a both commercial s-lens interface and a in-line dual ion funnel interface.

  10. Orthogonal Injection Ion Funnel Interface Providing Enhanced Performance for Selected Reaction Monitoring-Triple Quadruple Mass Spectrometry

    SciTech Connect

    Chen, Tsung-Chi; Fillmore, Thomas L.; Prost, Spencer A.; Moore, Ronald J.; Ibrahim, Yehia M.; Smith, Richard D.

    2015-07-21

    The electrodynamic ion funnel facilitates efficient focusing and transfer of charged particles in the higher pressure regions (e.g. ion source interfaces) of mass spectrometers, and thus providing increased sensitivity. An “off-axis” ion funnel design has been developed to reduce the source contamination and interferences from, e.g. ESI droplet residue and other poorly focused neutral or charged particles with very high mass-to charge ratios. In this study a dual ion funnel interface consisting of an orthogonal higher pressure electrodynamic ion funnel (HPIF) and an ion funnel trap combined with a triple quadruple mass spectrometer was developed and characterized. An orthogonal ion injection inlet and a repeller plate electrode was used to direct ions to an ion funnel HPIF at 9-10 Torr pressure. Several critical factors for the HPIF were characterized, including the effects of RF amplitude, DC gradient and operating pressure. Compared to the triple quadrupole standard interface more than 4-fold improvement in the limit of detection for the direct quantitative MS analysis of low abundance peptides was observed. The sensitivity enhancement in liquid chromatography selected reaction monitoring (SRM) analyses of low abundance peptides spiked into a highly complex mixture was also compared with that obtained using a both commercial s-lens interface and a in-line dual ion funnel interface.

  11. 18O-Labeled Proteome Reference as Global Internal Standards for Targeted Quantification by Selected Reaction Monitoring-Mass Spectrometry

    SciTech Connect

    Kim, Jong Seo; Fillmore, Thomas L.; Liu, Tao; Robinson, Errol W.; Hossain, Mahmud; Champion, Boyd L.; Moore, Ronald J.; Camp, David G.; Smith, Richard D.; Qian, Weijun

    2011-10-11

    Selected reaction monitoring-mass spectrometry (SRM-MS) is an emerging technology for high throughput targeted protein quantification and verification in biological and biomarker discovery studies; however, the cost associated with the use of stable isotope labeled synthetic peptides as internal standards is prohibitive for quantitatively screening large numbers of candidate proteins as often required in the pre-verification phase of biomarker discovery. Herein we present the proof-of-concept experiments of using an 18O-labeled 'universal' reference as comprehensive internal standards for quantitative SRM-MS analysis. With an 18O-labeled whole proteome sample as reference, every peptide of interest will have its own corresponding heavy isotope labeled internal standard, thus providing an ideal approach for quantitative screening of a large number of candidates using SRM-MS. Our results showed that the 18O incorporation efficiency using a recently improved protocol was >99.5% for most peptides investigated, a level comparable to 13C/15N labeled synthetic peptides in terms of heavy isotope incorporation. The accuracy, reproducibility, and linear dynamic range of quantification were further assessed based on known ratios of standard proteins spiked into mouse plasma with an 18O-labeled mouse plasma reference. A dynamic range of four orders of magnitude in relative concentration was obtained with high reproducibility (i.e., coefficient of variance <10%) based on the 16O/18O peak area ratios. Absolute and relative quantification of C-reactive protein and prostate-specific antigen were demonstrated by coupling an 18O-labeled reference with standard additions of protein standards. Collectively, our results demonstrated that the use of 18O-labeled reference provides a convenient and effective strategy for quantitative SRM screening of large number of candidate proteins.

  12. Peptides quantification by liquid chromatography with matrix-assisted laser desorption/ionization and selected reaction monitoring detection.

    PubMed

    Lesur, Antoine; Varesio, Emmanuel; Domon, Bruno; Hopfgartner, Gérard

    2012-10-01

    We present a novel analytical platform for peptides quantitative assays in biological matrices based on microscale liquid chromatography fractionation and matrix-assisted laser desorption/ionization mass spectrometric detection using the selected reaction monitoring (SRM) mode. The MALDI source was equipped with a high frequency Nd:YAG laser (1000 Hz) and mounted on a triple quadrupole/linear ion trap mass spectrometer (MALDI-QqQ(LIT)). Compared to conventional LC-ESI-SRM/MS, the separated analytes are "time-frozen" onto the MALDI plate in fractions, and navigation through the LC chromatogram makes it possible to perform SRM experiments as well as enhanced product ion spectra acquisition for confirmatory analyses without time constraints. The LC spots were analyzed using different rastering speeds ranging from 0.25 to 4 mm/sec with the shortest analysis time of 425 ms/spot. Since the LC runs can be multiplexed and do not need a comprehensive investigation, the present platform offers a valuable alternative to LC-ESI-SRM/MS for high throughput proteomic analyses. In addition, the derivatization of the N-terminal α-amino group by sulfonation was found to be key for the fragmentation of singly charged peptides under low collision energy regime. Under such conditions, y-ion series were observed in the MS/MS spectra, and thus the design of SRM experiments was greatly simplified. The quantitative performance of the platform was compared to that of LC-ESI-SRM/MS by spiking yeast tryptic peptides in human plasma digests. Both platforms exhibited similar sensitivities, accuracy (within ±20%) and precision (under 20%) in the relative quantification mode. As a proof of principle, the relative and absolute quantification of proteins associated with glycolysis, glyoxylate and tricarboxylic acid (TCA) cycles over a growth time course of Saccharomyces cerevisiae on glucose media was successfully performed using isotopic dilution. PMID:22897511

  13. Enhanced Sensitivity for Selected Reaction Monitoring Mass Spectrometry-based Targeted Proteomics Using a Dual Stage Electrodynamic Ion Funnel Interface*

    PubMed Central

    Hossain, Mahmud; Kaleta, David T.; Robinson, Errol W.; Liu, Tao; Zhao, Rui; Page, Jason S.; Kelly, Ryan T.; Moore, Ronald J.; Tang, Keqi; Camp, David G.; Qian, Wei-Jun; Smith, Richard D.

    2011-01-01

    Selected reaction monitoring mass spectrometry (SRM-MS) is playing an increasing role in quantitative proteomics and biomarker discovery studies as a method for high throughput candidate quantification and verification. Although SRM-MS offers advantages in sensitivity and quantification compared with other MS-based techniques, current SRM technologies are still challenged by detection and quantification of low abundance proteins (e.g. present at ∼10 ng/ml or lower levels in blood plasma). Here we report enhanced detection sensitivity and reproducibility for SRM-based targeted proteomics by coupling a nanospray ionization multicapillary inlet/dual electrodynamic ion funnel interface to a commercial triple quadrupole mass spectrometer. Because of the increased efficiency in ion transmission, significant enhancements in overall signal intensities and improved limits of detection were observed with the new interface compared with the original interface for SRM measurements of tryptic peptides from proteins spiked into non-depleted mouse plasma over a range of concentrations. Overall, average SRM peak intensities were increased by ∼70-fold. The average level of detection for peptides also improved by ∼10-fold with notably improved reproducibility of peptide measurements as indicated by the reduced coefficients of variance. The ability to detect proteins ranging from 40 to 80 ng/ml within mouse plasma was demonstrated for all spiked proteins without the application of front-end immunoaffinity depletion and fractionation. This significant improvement in detection sensitivity for low abundance proteins in complex matrices is expected to enhance a broad range of SRM-MS applications including targeted protein and metabolite validation. PMID:20410378

  14. ATAQS: A computational software tool for high throughput transition optimization and validation for selected reaction monitoring mass spectrometry

    PubMed Central

    2011-01-01

    Background Since its inception, proteomics has essentially operated in a discovery mode with the goal of identifying and quantifying the maximal number of proteins in a sample. Increasingly, proteomic measurements are also supporting hypothesis-driven studies, in which a predetermined set of proteins is consistently detected and quantified in multiple samples. Selected reaction monitoring (SRM) is a targeted mass spectrometric technique that supports the detection and quantification of specific proteins in complex samples at high sensitivity and reproducibility. Here, we describe ATAQS, an integrated software platform that supports all stages of targeted, SRM-based proteomics experiments including target selection, transition optimization and post acquisition data analysis. This software will significantly facilitate the use of targeted proteomic techniques and contribute to the generation of highly sensitive, reproducible and complete datasets that are particularly critical for the discovery and validation of targets in hypothesis-driven studies in systems biology. Result We introduce a new open source software pipeline, ATAQS (Automated and Targeted Analysis with Quantitative SRM), which consists of a number of modules that collectively support the SRM assay development workflow for targeted proteomic experiments (project management and generation of protein, peptide and transitions and the validation of peptide detection by SRM). ATAQS provides a flexible pipeline for end-users by allowing the workflow to start or end at any point of the pipeline, and for computational biologists, by enabling the easy extension of java algorithm classes for their own algorithm plug-in or connection via an external web site. This integrated system supports all steps in a SRM-based experiment and provides a user-friendly GUI that can be run by any operating system that allows the installation of the Mozilla Firefox web browser. Conclusions Targeted proteomics via SRM is a powerful

  15. Bioanalytical high-throughput selected reaction monitoring-LC/MS determination of selected estrogen receptor modulators in human plasma: 2000 samples/day.

    PubMed

    Zweigenbaum, J; Henion, J

    2000-06-01

    The high-throughput determination of small molecules in biological matrixes has become an important part of drug discovery. This work shows that increased throughput LC/MS/MS techniques can be used for the analysis of selected estrogen receptor modulators in human plasma where more than 2000 samples may be analyzed in a 24-h period. The compounds used to demonstrate the high-throughput methodology include tamoxifen, raloxifene, 4-hydroxytamoxifen, nafoxidine, and idoxifene. Tamoxifen and raloxifene are used in both breast cancer therapy and osteoporosis and have shown prophylactic potential for the reduction of the risk of breast cancer. The described strategy provides LC/MS/MS separation and quantitation for each of the five test articles in control human plasma. The method includes sample preparation employing liquid-liquid extraction in the 96-well format, an LC separation of the five compounds in less than 30 s, and selected reaction monitoring detection from low nano- to microgram per milliter levels. Precision and accuracy are determined where each 96-well plate is considered a typical "tray" having calibration standards and quality control (QC) samples dispersed through each plate. A concept is introduced where 24 96-well plates analyzed in 1 day is considered a "grand tray", and the method is cross-validated with standards placed only at the beginning of the first plate and the end of the last plate. Using idoxifene-d5 as an internal standard, the results obtained for idoxifene and tamoxifen satisfy current bioanalytical method validation criteria on two separate days where 2112 and 2304 samples were run, respectively. Method validation included 24-h autosampler stability and one freeze-thaw cycle stability for the extracts. Idoxifene showed acceptable results with accuracy ranging from 0.3% for the high quality control (QC) to 15.4% for the low QC and precision of 3.6%-13.9% relative standard deviation. Tamoxifen showed accuracy ranging from 1.6% to 13

  16. Simultaneous selected reaction monitoring, MS/MS and MS3 quantitation for the analysis of pharmaceutical compounds in human plasma using chip-based infusion.

    PubMed

    Leuthold, Luc Alexis; Grivet, Chantal; Allen, Mark; Baumert, Mark; Hopfgartner, Gérard

    2004-01-01

    An assay method with mass spectrometric detection was developed for the quantitative analysis of a pharmaceutical compound and its major metabolite in human plasma using chip-based infusion. Liquid-liquid extraction sample preparation was found to be essential to minimize matrix suppression and to achieve a limit of quantitation (LOQ) of 2.5 ng/mL using a 100 microL plasma aliquot. The potential for simultaneous quantitation in selected reaction monitoring (SRM), tandem mass spectrometry (MS/MS) (enhanced product ion), and MS(3) was investigated and found to be very beneficial in improving assay selectivity. A novel concept for monitoring quantitative assay performance using a SRM/MS(3) ratio is proposed. PMID:15329867

  17. Reaction Selectivity in Heterogeneous Catalysis

    SciTech Connect

    Somorjai, Gabor A.; Kliewer, Christopher J.

    2009-02-02

    The understanding of selectivity in heterogeneous catalysis is of paramount importance to our society today. In this review we outline the current state of the art in research on selectivity in heterogeneous catalysis. Current in-situ surface science techniques have revealed several important features of catalytic selectivity. Sum frequency generation vibrational spectroscopy has shown us the importance of understanding the reaction intermediates and mechanism of a heterogeneous reaction, and can readily yield information as to the effect of temperature, pressure, catalyst geometry, surface promoters, and catalyst composition on the reaction mechanism. DFT calculations are quickly approaching the ability to assist in the interpretation of observed surface spectra, thereby making surface spectroscopy an even more powerful tool. HP-STM has revealed three vitally important parameters in heterogeneous selectivity: adsorbate mobility, catalyst mobility, and selective site-blocking. The development of size controlled nanoparticles from 0.8 to 10 nm, of controlled shape, and of controlled bimetallic composition has revealed several important variables for catalytic selectivity. Lastly, DFT calculations may be paving the way to guiding the composition choice for multi-metallic heterogeneous catalysis for the intelligent design of catalysts incorporating the many factors of selectivity we have learned.

  18. A Label-free Selected Reaction Monitoring Workflow Identifies a Subset of Pregnancy Specific Glycoproteins as Potential Predictive Markers of Early-onset Pre-eclampsia*

    PubMed Central

    Blankley, Richard T.; Fisher, Christal; Westwood, Melissa; North, Robyn; Baker, Philip N.; Walker, Michael J.; Williamson, Andrew; Whetton, Anthony D.; Lin, Wanchang; McCowan, Lesley; Roberts, Claire T.; Cooper, Garth J. S.; Unwin, Richard D.; Myers, Jenny E.

    2013-01-01

    Pre-eclampsia (PE) is a serious complication of pregnancy with potentially life threatening consequences for both mother and baby. Presently there is no test with the required performance to predict which healthy first-time mothers will go on to develop PE. The high specificity, sensitivity, and multiplexed nature of selected reaction monitoring holds great potential as a tool for the verification and validation of putative candidate biomarkersfor disease states. Realization of this potential involves establishing a high throughput, cost effective, reproducible sample preparation workflow. We have developed a semi-automated HPLC-based sample preparation workflow before a label-free selected reaction monitoring approach. This workflow has been applied to the search for novel predictive biomarkers for PE. To discover novel candidate biomarkers for PE, we used isobaric tagging to identify several potential biomarker proteins in plasma obtained at 15 weeks gestation from nulliparous women who later developed PE compared with pregnant women who remained healthy. Such a study generates a number of “candidate” biomarkers that require further testing in larger patient cohorts. As proof-of-principle, two of these proteins were taken forward for verification in a 100 women (58 PE, 42 controls) using label-free SRM. We obtained reproducible protein quantitation across the 100 samples and demonstrated significant changes in protein levels, even with as little as 20% change in protein concentration. The SRM data correlated with a commercial ELISA, suggesting that this is a robust workflow suitable for rapid, affordable, label-free verification of which candidate biomarkers should be taken forward for thorough investigation. A subset of pregnancy-specific glycoproteins (PSGs) had value as novel predictive markers for PE. PMID:23897580

  19. Fast and selective determination of triterpenic compounds in olive leaves by liquid chromatography-tandem mass spectrometry with multiple reaction monitoring after microwave-assisted extraction.

    PubMed

    Sánchez-Avila, N; Priego-Capote, F; Ruiz-Jiménez, J; de Castro, M D Luque

    2009-04-15

    A method for fast and selective determination of the main triterpenic compounds present in olive leaves - oleanolic, ursolic and maslinic acids as triterpenic acids and, uvaol and erythrodiol as triterpenic dialcohols - is reported here. Quantitative isolation of the analytes has been accomplished in 5min by microwave assistance using ethanol as extractant. Due to the medium polarity of triterpenic acids and dialcohols, different ethanol-water ratios were tested in order to select the optimum extractant composition for their solubilisation. Microwave assistance provided a significant shortening of the leaching time as compared to conventional procedures by maceration, which usually requires at least 5h. After extraction, determination was carried out by liquid chromatography-tandem mass spectrometry (LC-MS-MS) with a triple quadrupole (qQq) mass detector without any clean-up step prior to chromatographic analysis. Highly selective identification of triterpenes was confirmed by multiple reaction monitoring (MRM) using the most representative transitions from the precursor ion to the different product ions, while the most sensitive transitions were used for MS-MS quantitation. Total analysis performed in 25 min enables the characterization of a fraction with particular interest in the pharmacological area. PMID:19174200

  20. Immunoaffinity enrichment and liquid chromatography-selected reaction monitoring mass spectrometry for quantitation of carbonic anhydrase 12 in cultured renal carcinoma cells

    PubMed Central

    Rafalko, Agnes; Iliopoulos, Othon; Fusaro, Vincent A.; Hancock, William; Hincapie, Marina

    2010-01-01

    Liquid chromatography-selected reaction monitoring (LC-SRM) is a highly specific and sensitive mass spectrometry (MS) technique that is widely being applied to selectively qualify and validate candidate markers within complex biological samples. However, in order for LC-SRM methods to take on these attributes, target-specific optimization of sample processing is required, in order to reduce analyte complexity, prior to LC-SRM. In this study, we have developed a targeted platform consisting of protein immunoaffinity enrichment on magnetic beads and LC-SRM for measuring carbonic anhydrase 12 (CA12) protein in a renal cell carcinoma (RCC) cell line (PRC3), a candidate biomarker for RCC whose expression at the protein level has not been previously reported. Sample processing and LC-SRM assay were optimized for signature peptides selected as surrogate markers of CA12 protein. Using LC-SRM coupled with stable isotope dilution, we achieved limits of quantitation in the low fmol range sufficient for measuring clinically relevant biomarkers with good intra- and inter-assay accuracy and precision (≤17%). Our results show that using a quantitative immunoaffinity capture approach provides specific, accurate, and robust assays amenable to high-throughput verification of potential biomarkers. PMID:20936840

  1. Immunoaffinity enrichment and liquid chromatography-selected reaction monitoring mass spectrometry for quantitation of carbonic anhydrase 12 in cultured renal carcinoma cells.

    PubMed

    Rafalko, Agnes; Iliopoulos, Othon; Fusaro, Vincent A; Hancock, William; Hincapie, Marina

    2010-11-01

    Liquid chromatography-selected reaction monitoring (LC-SRM) is a highly specific and sensitive mass spectrometry (MS) technique that is widely being applied to selectively qualify and validate candidate markers within complex biological samples. However, in order for LC-SRM methods to take on these attributes, target-specific optimization of sample processing is required, in order to reduce analyte complexity, prior to LC-SRM. In this study, we have developed a targeted platform consisting of protein immunoaffinity enrichment on magnetic beads and LC-SRM for measuring carbonic anhydrase 12 (CA12) protein in a renal cell carcinoma (RCC) cell line (PRC3), a candidate biomarker for RCC whose expression at the protein level has not been previously reported. Sample processing and LC-SRM assay were optimized for signature peptides selected as surrogate markers of CA12 protein. Using LC-SRM coupled with stable isotope dilution, we achieved limits of quantitation in the low fmol range sufficient for measuring clinically relevant biomarkers with good intra- and interassay accuracy and precision (≤17%). Our results show that using a quantitative immunoaffinity capture approach provides specific, accurate, and robust assays amenable to high-throughput verification of potential biomarkers. PMID:20936840

  2. Multi-mycotoxin analysis of animal feed and animal-derived food using LC-MS/MS system with timed and highly selective reaction monitoring.

    PubMed

    Zhao, Zhiyong; Liu, Na; Yang, Lingchen; Deng, Yifeng; Wang, Jianhua; Song, Suquan; Lin, Shanhai; Wu, Aibo; Zhou, Zhenlei; Hou, Jiafa

    2015-09-01

    Mycotoxins have the potential to enter the human food chain through carry-over of contaminants from feed into animal-derived products. The objective of the study was to develop a reliable and sensitive method for the analysis of 30 mycotoxins in animal feed and animal-derived food (meat, edible animal tissues, and milk) using liquid chromatography-tandem mass spectrometry (LC-MS/MS). In the study, three extraction procedures, as well as various cleanup procedures, were evaluated to select the most suitable sample preparation procedure for different sample matrices. In addition, timed and highly selective reaction monitoring on LC-MS/MS was used to filter out isobaric matrix interferences. The performance characteristics (linearity, sensitivity, recovery, precision, and specificity) of the method were determined according to Commission Decision 2002/657/EC and 401/2006/EC. The established method was successfully applied to screening of mycotoxins in animal feed and animal-derived food. The results indicated that mycotoxin contamination in feed directly influenced the presence of mycotoxin in animal-derived food. Graphical abstract Multi-mycotoxin analysis of animal feed and animal-derived food using LC-MS/MS. PMID:26198112

  3. Dilute and shoot: analysis of drugs of abuse using selected reaction monitoring for quantification and full scan product ion spectra for identification.

    PubMed

    Fitzgerald, Robert L; Griffin, Terrance L; Yun, Yeo-Min; Godfrey, Richard A; West, Robert; Pesce, Amadeo J; Herold, David A

    2012-03-01

    Our objective was to develop a "dilute and shoot" liquid chromatography-tandem mass spectrometry confirmatory procedure that uses full scan product ion spectra to identify drugs that are present above cutoff values as determined by isotope dilution relative to a deuterium-labeled internal standard. Deuterium-labeled internal standards are added to urine which is then diluted prior to analysis. Full scan product ion spectra were obtained in the data-dependent mode using a linear ion trap (ABI 4000 Qtrap). Identification was based on a purity fit of greater than 70. Ninety-seven urine specimens were analyzed by the method described, and results were compared to values obtained from a reference laboratory using selected reaction monitoring (SRM). The ion trap provided about 30-fold increase in signal-to-noise ratio as compared with the same instrument operated in a traditional full scan product ion mode. The assays were linear to at least 10 times the cutoff. Selecting appropriate triggers for obtaining full scan product ion spectra minimized space charging for specimens that contained high concentrations of drugs. There was 100% concordance between the full scan identification and the SRM results for identification of amphetamine, methamphetamine, benzoylecgonine, morphine, codeine, hydrocodone, and hydromorphone. The ability to "dilute and shoot" reduces the turnaround time for results. The data acquired with SRM and full scan product ion spectra provide accurate quantification and a high degree of specificity. PMID:22337779

  4. Ultra-fast quantitation of saquinavir in human plasma by matrix-assisted laser desorption/ionization and selected reaction monitoring mode detection.

    PubMed

    Wagner, Michel; Varesio, Emmanuel; Hopfgartner, Gérard

    2008-09-01

    We present herein an ultra-fast quantitative assay for the quantitation of saquinavir in human plasma, without prior chromatographic separation, with matrix-assisted laser desorption/ionization using the selected reaction monitoring quantitation mode (MALDI-SRM/MS). The method was found to be linear from 5 to 10,000 ng/ml using pentadeuterated saquinavir (SQV-d5) as an internal standard, and from 5 to 1000 ng/ml using reserpine as internal standard (IS). Accuracy and precision were in the range of 101-108%, 3.9-11% with SQV-d5 and in the range 93-108%, 3.5-15% with reserpine. Plasma samples (250 microl) were extracted with a mixture of ethyl acetate/hexane. MALDI spotting of the extract was automated using electrodeposition and the dried droplet method using alpha-cyano-4-hydroxycinnamic acid (CHCA) as matrix. A 96 spots MALDI plate was prepared within 20 min in a fully unattended manner. Each sample was spotted four times and quantitation was based on the average of their analyte/IS area ratio. Samples were analyzed on a triple quadrupole linear ion trap (QqQ(LIT)) equipped with a high repetition laser source (1000 Hz). The analysis time of one sample was approximately 6 s, therefore 96 samples could be analyzed in less than 10 min. With liquid-liquid extraction sample preparation no significant matrix effects were observed. Moreover, the assay showed sufficient selectivity for samples to be analyzed at the lower limit of quantification (LLOQ) in the presence of other antiretroviral drugs, without prior chromatographic steps. In parallel, to assess the selectivity of the assay with real samples, a liquid chromatography (LC)-SRM/MS method was developed and a cross validation with clinical samples was successfully performed. PMID:18657486

  5. A Quantitative Proteomic Profile of the Nrf2-Mediated Antioxidant Response of Macrophages to Oxidized LDL Determined by Multiplexed Selected Reaction Monitoring

    PubMed Central

    Kinter, Caroline S.; Lundie, Jillian M.; Patel, Halee; Rindler, Paul M.; Szweda, Luke I.; Kinter, Michael

    2012-01-01

    The loading of macrophages with oxidized low density lipoprotein (LDL) is a key part of the initiation and progression of atherosclerosis. Oxidized LDL contains a wide ranging set of toxic species, yet the molecular events that allow macrophages to withstand loading with these toxic species are not completely characterized. The transcription factor nuclear factor (erythroid-derived 2)-like 2 (Nrf2) is a master regulator of the cellular stress response. However, the specific parts of the Nrf2-dependent stress response are diverse, with both tissue- and treatment-dependent components. The goal of these experiments was to develop and use a quantitative proteomic approach to characterize the Nrf2-dependent response in macrophages to oxidized LDL. Cultured mouse macrophages, the J774 macrophage-like cell line, were treated with a combination of oxidized LDL, the Nrf2-stabilizing reagent tert- butylhydroquinone (tBHQ), and/or Nrf2 siRNA. Protein expression was determined using a quantitative proteomics assay based on selected reaction monitoring. The assay was multiplexed to monitor a set of 28 antioxidant and stress response proteins, 6 housekeeping proteins, and 1 non-endogenous standard protein. The results have two components. The first component is the validation of the multiplexed, quantitative proteomics assay. The assay is shown to be fundamentally quantitative, precise, and accurate. The second component is the characterization of the Nrf2-mediated stress response. Treatment with tBHQ and/or Nrf2 siRNA gave statistically significant changes in the expression of a subset of 11 proteins. Treatment with oxidized LDL gave statistically significant increases in the expression of 7 of those 11 proteins plus one additional protein. All of the oxLDL-mediated increases were attenuated by Nrf2 siRNA. These results reveal a specific, multifaceted response of the foam cells to the incoming toxic oxidized LDL. PMID:23166812

  6. Liquid chromatography-selected reaction monitoring (LC-SRM) approach for the separation and quantitation of sialylated N-glycans linkage isomers.

    PubMed

    Tao, Shujuan; Huang, Yining; Boyes, Barry E; Orlando, Ron

    2014-11-01

    The study of N-linked glycans is among the most challenging bioanalytical tasks because of their complexity and variety. The presence of glycoform families that differ only in branching and/or linkage position makes the identification and quantitation of individual glycans exceedingly difficult. Quantitation of these individual glycans is important because changes in the abundance of these isomers are often associated with significant biomedical events. For instance, previous studies have shown that the ratio of α2-3 to α2-6 linked sialic acid (SA) plays an important role in cancer biology. Consequently, quantitative methods to detect alterations in the ratios of glycans based on their SA linkages could serve as a diagnostic tool in oncology, yet traditional glycomic profiling cannot readily differentiate between these linkage isomers. Here, we present a liquid chromatography-selected reaction monitoring (LC-SRM) approach that we demonstrate is capable of quantitating the individual SA linkage isomers. The LC method is capable of separating sialylated N-glycan isomers differing in α2-3 and α2-6 linkages using a novel superficially porous particle (Fused-Core) Penta-HILIC (hydrophilic interaction liquid chromatography) column. SRM detection provides the relative quantitation of each SA linkage isomer, and minimizes interferences from coeluting glycans that are problematic for UV/Fluorescence based quantitation. With our approach, the relative quantitation of each SA linkage isomer is obtained from a straightforward liquid chromatography-mass spectrometry (LC-MS) experiment. PMID:25299151

  7. Immunocapture-Selected Reaction Monitoring Screening Facilitates the Development of ELISA for the Measurement of Native TEX101 in Biological Fluids*

    PubMed Central

    Korbakis, Dimitrios; Brinc, Davor; Schiza, Christina; Soosaipillai, Antoninus; Jarvi, Keith; Drabovich, Andrei P.; Diamandis, Eleftherios P.

    2015-01-01

    Monoclonal antibodies that bind the native conformation of proteins are indispensable reagents for the development of immunoassays, production of therapeutic antibodies and delineating protein interaction networks by affinity purification-mass spectrometry. Antibodies generated against short peptides, protein fragments, or even full length recombinant proteins may not bind the native protein form in biological fluids, thus limiting their utility. Here, we report the application of immunocapture coupled with selected reaction monitoring measurements (immunocapture-SRM), in the rapid screening of hybridoma culture supernatants for monoclonal antibodies that bind the native protein conformation. We produced mouse monoclonal antibodies, which detect in human serum or seminal plasma the native form of the human testis-expressed sequence 101 (TEX101) protein—a recently proposed biomarker of male infertility. Pairing of two monoclonal antibodies against unique TEX101 epitopes led to the development of an ELISA for the measurement of TEX101 in seminal plasma (limit of detection: 20 pg/ml) and serum (limit of detection: 40 pg/ml). Measurements of matched seminal plasma samples, obtained from men pre- and post-vasectomy, confirmed the absolute diagnostic specificity and sensitivity of TEX101 for noninvasive identification of physical obstructions in the male reproductive tract. Measurement of male and female serum samples revealed undetectable levels of TEX101 in the systemic circulation of healthy individuals. Immunocapture-SRM screening may facilitate development of monoclonal antibodies and immunoassays against native forms of challenging protein targets. PMID:25813379

  8. Liquid Chromatography-Selected Reaction Monitoring (LC-SRM) Approach for the Separation and Quantitation of Sialylated N-Glycans Linkage Isomers

    PubMed Central

    2015-01-01

    The study of N-linked glycans is among the most challenging bioanalytical tasks because of their complexity and variety. The presence of glycoform families that differ only in branching and/or linkage position makes the identification and quantitation of individual glycans exceedingly difficult. Quantitation of these individual glycans is important because changes in the abundance of these isomers are often associated with significant biomedical events. For instance, previous studies have shown that the ratio of α2-3 to α2-6 linked sialic acid (SA) plays an important role in cancer biology. Consequently, quantitative methods to detect alterations in the ratios of glycans based on their SA linkages could serve as a diagnostic tool in oncology, yet traditional glycomic profiling cannot readily differentiate between these linkage isomers. Here, we present a liquid chromatography-selected reaction monitoring (LC-SRM) approach that we demonstrate is capable of quantitating the individual SA linkage isomers. The LC method is capable of separating sialylated N-glycan isomers differing in α2-3 and α2-6 linkages using a novel superficially porous particle (Fused-Core) Penta-HILIC (hydrophilic interaction liquid chromatography) column. SRM detection provides the relative quantitation of each SA linkage isomer, and minimizes interferences from coeluting glycans that are problematic for UV/Fluorescence based quantitation. With our approach, the relative quantitation of each SA linkage isomer is obtained from a straightforward liquid chromatography-mass spectrometry (LC-MS) experiment. PMID:25299151

  9. Immunocapture-Selected Reaction Monitoring Screening Facilitates the Development of ELISA for the Measurement of Native TEX101 in Biological Fluids.

    PubMed

    Korbakis, Dimitrios; Brinc, Davor; Schiza, Christina; Soosaipillai, Antoninus; Jarvi, Keith; Drabovich, Andrei P; Diamandis, Eleftherios P

    2015-06-01

    Monoclonal antibodies that bind the native conformation of proteins are indispensable reagents for the development of immunoassays, production of therapeutic antibodies and delineating protein interaction networks by affinity purification-mass spectrometry. Antibodies generated against short peptides, protein fragments, or even full length recombinant proteins may not bind the native protein form in biological fluids, thus limiting their utility. Here, we report the application of immunocapture coupled with selected reaction monitoring measurements (immunocapture-SRM), in the rapid screening of hybridoma culture supernatants for monoclonal antibodies that bind the native protein conformation. We produced mouse monoclonal antibodies, which detect in human serum or seminal plasma the native form of the human testis-expressed sequence 101 (TEX101) protein-a recently proposed biomarker of male infertility. Pairing of two monoclonal antibodies against unique TEX101 epitopes led to the development of an ELISA for the measurement of TEX101 in seminal plasma (limit of detection: 20 pg/ml) and serum (limit of detection: 40 pg/ml). Measurements of matched seminal plasma samples, obtained from men pre- and post-vasectomy, confirmed the absolute diagnostic specificity and sensitivity of TEX101 for noninvasive identification of physical obstructions in the male reproductive tract. Measurement of male and female serum samples revealed undetectable levels of TEX101 in the systemic circulation of healthy individuals. Immunocapture-SRM screening may facilitate development of monoclonal antibodies and immunoassays against native forms of challenging protein targets. PMID:25813379

  10. Long-Gradient Separations Coupled with Selected Reaction Monitoring for Highly Sensitive, Large Scale Targeted Protein Quantification in a Single Analysis

    SciTech Connect

    Shi, Tujin; Fillmore, Thomas L.; Gao, Yuqian; Zhao, Rui; He, Jintang; Schepmoes, Athena A.; Nicora, Carrie D.; Wu, Chaochao; Chambers, Justin L.; Moore, Ronald J.; Kagan, Jacob; Srivastava, Sudhir; Liu, Alvin Y.; Rodland, Karin D.; Liu, Tao; Camp, David G.; Smith, Richard D.; Qian, Weijun

    2013-10-01

    Long-gradient separations coupled to tandem MS were recently demonstrated to provide a deep proteome coverage for global proteomics; however, such long-gradient separations have not been explored for targeted proteomics. Herein, we investigate the potential performance of the long-gradient separations coupled with selected reaction monitoring (LG-SRM) for targeted protein quantification. Direct comparison of LG-SRM (5 h gradient) and conventional LC-SRM (45 min gradient) showed that the long-gradient separations significantly reduced background interference levels and provided an 8- to 100-fold improvement in LOQ for target proteins in human female serum. Based on at least one surrogate peptide per protein, an LOQ of 10 ng/mL was achieved for the two spiked proteins in non-depleted human serum. The LG-SRM detection of seven out of eight endogenous plasma proteins expressed at ng/mL or sub-ng/mL levels in clinical patient sera was also demonstrated. A correlation coefficient of >0.99 was observed for the results of LG-SRM and ELISA measurements for prostate-specific antigen (PSA) in selected patient sera. Further enhancement of LG-SRM sensitivity was achieved by applying front-end IgY14 immunoaffinity depletion. Besides improved sensitivity, LG-SRM offers at least 3 times higher multiplexing capacity than conventional LC-SRM due to ~3-fold increase in average peak widths for a 300-min gradient compared to a 45-min gradient. Therefore, LG-SRM holds great potential for bridging the gap between global and targeted proteomics due to its advantages in both sensitivity and multiplexing capacity.

  11. A selected reaction monitoring-based analysis of acute phase proteins in interstitial fluids from experimental equine wounds healing by secondary intention.

    PubMed

    Bundgaard, Louise; Bendixen, Emøke; Sørensen, Mette Aa; Harman, Victoria M; Beynon, Robert J; Petersen, Lars J; Jacobsen, Stine

    2016-05-01

    In horses, pathological healing with formation of exuberant granulation tissue (EGT) is a particular problem in limb wounds, whereas body wounds tend to heal without complications. Chronic inflammation has been proposed to be central to the pathogenesis of EGT. This study aimed to investigate levels of inflammatory acute phase proteins (APPs) in interstitial fluid from wounds in horses. A novel approach for absolute quantification of proteins, selected reaction monitoring (SRM)-based mass spectrometry in combination with a quantification concatamer (QconCAT), was used for the quantification of five established equine APPs (fibrinogen, serum amyloid A, ceruloplasmin, haptoglobin, and plasminogen) and three proposed equine APPs (prothrombin, α-2-macroglobulin, and α-1-antitrypsin). Wound interstitial fluid was recovered by large pore microdialysis from experimental body and limb wounds from five horses at days 1, 2, 7, and 14 after wounding and healing without (body) and with (limb) the formation of EGT. The QconCAT included proteotypic peptides representing each of the protein targets and was used to direct the design of a gene, which was expressed in Escherichia coli in a media supplemented with stable isotopes for metabolically labeling of standard peptides. Co-analysis of wound interstitial fluid samples with the stable isotope-labeled QconCAT tryptic peptides in known amounts enabled quantification of the APPs in absolute terms. The concentrations of fibrinogen, haptoglobin, ceruloplasmin, prothrombin, and α-1-antitrypsin in dialysate from limb wounds were significantly higher than in dialysate from body wounds. This is the first report of simultaneous analysis of a panel of APPs using the QconCAT-SRM technology. The microdialysis technique in combination with the QconCAT-SRM-based approach proved useful for quantification of the investigated proteins in the wound interstitial fluid, and the results indicated that there is a state of sustained inflammation in

  12. Quantification in MALDI-MS imaging: what can we learn from MALDI-selected reaction monitoring and what can we expect for imaging?

    PubMed

    Porta, Tiffany; Lesur, Antoine; Varesio, Emmanuel; Hopfgartner, Gérard

    2015-03-01

    Quantification by mass spectrometry imaging (Q-MSI) is one of the hottest topics of the current discussions among the experts of the MS imaging community. If MSI is established as a powerful qualitative tool in drug and biomarker discovery, its reliability for absolute and accurate quantification (QUAN) is still controversial. Indeed, Q-MSI has to deal with several fundamental aspects that are difficult to control, and to account for absolute quantification. The first objective of this manuscript is to review the state-of-the-art of Q-MSI and the current strategies developed for absolute quantification by direct surface sampling from tissue sections. This includes comments on the quest for the perfect matrix-matched standards and signal normalization approaches. Furthermore, this work investigates quantification at a pixel level to determine how many pixels must be considered for accurate quantification by ultraviolet matrix-assisted laser desorption/ionization (MALDI), the most widely used technique for MSI. Particularly, this study focuses on the MALDI-selected reaction monitoring (SRM) in rastering mode, previously demonstrated as a quantitative and robust approach for small analyte and peptide-targeted analyses. The importance of designing experiments of good quality and the use of a labeled compound for signal normalization is emphasized to minimize the signal variability. This is exemplified by measuring the signal for cocaine and a tryptic peptide (i.e., obtained after digestion of a monoclonal antibody) upon different experimental conditions, such as sample stage velocity, laser power and frequency, or distance between two raster lines. Our findings show that accurate quantification cannot be performed on a single pixel but requires averaging of at least 4-5 pixels. The present work demonstrates that MALDI-SRM/MSI is quantitative with precision better than 10-15 %, which meets the requirements of most guidelines (i.e., in bioanalysis or toxicology) for

  13. A critical assessment of the performance criteria in confirmatory analysis for veterinary drug residue analysis using mass spectrometric detection in selected reaction monitoring mode.

    PubMed

    Berendsen, Bjorn J A; Meijer, Thijs; Wegh, Robin; Mol, Hans G J; Smyth, Wesley G; Armstrong Hewitt, S; van Ginkel, Leen; Nielen, Michel W F

    2016-05-01

    Besides the identification point system to assure adequate set-up of instrumentation, European Commission Decision 2002/657/EC includes performance criteria regarding relative ion abundances in mass spectrometry and chromatographic retention time. In confirmatory analysis, the relative abundance of two product ions, acquired in selected reaction monitoring mode, the ion ratio should be within certain ranges for confirmation of the identity of a substance. The acceptable tolerance of the ion ratio varies with the relative abundance of the two product ions and for retention time, CD 2002/657/EC allows a tolerance of 5%. Because of rapid technical advances in analytical instruments and new approaches applied in the field of contaminant testing in food products (multi-compound and multi-class methods) a critical assessment of these criteria is justified. In this study a large number of representative, though challenging sample extracts were prepared, including muscle, urine, milk and liver, spiked with 100 registered and banned veterinary drugs at levels ranging from 0.5 to 100 µg/kg. These extracts were analysed using SRM mode using different chromatographic conditions and mass spectrometers from different vendors. In the initial study, robust data was collected using four different instrumental set-ups. Based on a unique and highly relevant data set, consisting of over 39 000 data points, the ion ratio and retention time criteria for applicability in confirmatory analysis were assessed. The outcomes were verified based on a collaborative trial including laboratories from all over the world. It was concluded that the ion ratio deviation is not related to the value of the ion ratio, but rather to the intensity of the lowest product ion. Therefore a fixed ion ratio deviation tolerance of 50% (relative) is proposed, which also is applicable for compounds present at sub-ppb levels or having poor ionisation efficiency. Furthermore, it was observed that retention time

  14. Quantification of activated NF-kappaB/RelA complexes using ssDNA aptamer affinity-stable isotope dilution-selected reaction monitoring-mass spectrometry.

    PubMed

    Zhao, Yingxin; Widen, Steven G; Jamaluddin, Mohammad; Tian, Bing; Wood, Thomas G; Edeh, Chukwudi B; Brasier, Allan R

    2011-06-01

    Nuclear Factor-κB (NF-κB) is a family of inducible transcription factors regulated by stimulus-induced protein interactions. In the cytoplasm, the NF-κB member RelA transactivator is inactivated by binding inhibitory IκBs, whereas in its activated state, the serine-phosphorylated protein binds the p300 histone acetyltransferase. Here we describe the isolation of a ssDNA aptamer (termed P028F4) that binds to the activated (IκBα-dissociated) form of RelA with a K(D) of 6.4 × 10(-10), and its application in an enrichment-mass spectrometric quantification assay. ssDNA P028F4 competes with cognate duplex high affinity NF-κB binding sites for RelA binding in vitro, binds activated RelA in eukaryotic nuclei and reduces TNFα-stimulated endogenous NF-κB dependent gene expression. Incorporation of P028F4 as an affinity isolation step enriches for serine 536 phosphorylated and p300 coactivator complexed RelA, simultaneously depleting IκBα·RelA complexes. A stable isotope dilution (SID)-selected reaction monitoring (SRM)- mass spectrometry (MS) assay for RelA was developed that produced a linear response over 1,000 fold dilution range of input protein and had a 200 amol lower limit of quantification. This multiplex SID-SRM-MS RelA assay was used to quantify activated endogenous RelA in cytokine-stimulated eukaryotic cells isolated by single-step P028F4 enrichment. The aptamer-SID-SRM-MS assay quantified the fraction of activated RelA in subcellular extracts, detecting the presence of a cytoplasmic RelA reservoir unresponsive to TNFα stimulation. We conclude that aptamer-SID-SRM-MS is a versatile tool for quantification of activated NF-κB/RelA and its associated complexes in response to pathway activation. PMID:21502374

  15. Selective simulation and selective sensor interpretation in monitoring

    NASA Technical Reports Server (NTRS)

    Doyle, Richard J.; Berleant, Daniel; Falcone, Loretta P.; Fayyad, Usama M.

    1989-01-01

    An approach to selective processing in monitoring is described. The approach is designed to provide informative feedback on whether a system is performing nominally in the current operating context without exceeding available resources for prediction and interpretation. At the center of the approach to selective sensor interpretation and simulation is a causal model of the system being monitored. The architecture of the monitoring system, called PREMON, is described as well as how causal models of physical systems are represented and simulated.

  16. Capillary Electrophoresis-Nanoelectrospray Ionization-Selected Reaction Monitoring Mass Spectrometry via a True Sheathless Metal-Coated Emitter Interface for Robust and High-Sensitivity Sample Quantification.

    PubMed

    Guo, Xuejiang; Fillmore, Thomas L; Gao, Yuqian; Tang, Keqi

    2016-04-19

    A new sheathless transient capillary isotachophoresis (CITP)/capillary zone electrophoresis (CZE)-MS interface, based on a commercially available capillary with an integrated metal-coated ESI emitter, was developed in this study aiming at overcoming the reproducibility and ruggedness problems suffered to a certain degree by almost all the available CE-MS interfaces, and pushing the CE-MS technology suitable for routine sample analysis with high sensitivity. The new CITP/CZE-MS interface allows the electric contact between ESI voltage power supply and the CE separation liquid by using a conductive liquid that comes in contact with the metal-coated surface of the ESI emitter, making it a true sheathless CE-MS interface. Stable electrospray was established by avoiding the formation of gas bubbles from electrochemical reaction inside the CE capillary. Crucial operating parameters, such as sample loading volume, flow rate, and separation voltage, were systematically evaluated for their effects on both CITP/CZE separation efficiency and MS detection sensitivity. Around one hundred CITP/CZE-MS analyses can be easily achieved by using the new sheathless CITP/CZE interface without a noticeable loss of metal coating on the ESI emitter surface, or degrading of the ESI emitter performance. The reproducibility in analyte migration time and quantitative performance of the new interface was experimentally evaluated to demonstrate a LOQ below 5 attomole. PMID:27028594

  17. Monitoring enzymatic reactions with in situ sensors

    NASA Astrophysics Data System (ADS)

    Young, Ian T.; Iordanov, V.; Kroon, Arthur; Dietrich, Heidi R. C.; Moerman, R.; van den Doel, L. R.; van Dedem, G. W. K.; Bossche, Andre; Gray, Bonnie L.; Sarro, Lina; Verbeek, Piet W.; van Vliet, Lucas J.

    2003-07-01

    In previous publications and presentations we have described our construction of a laboratory-on-a-chip based on nanoliter capacity wells etched in silicon. We have described methods for dispensing reagents as well as samples, for preventing evaporation, for embedding electronics in each well to measure fluid volume per well in real-time, and for monitoring the production or consumption of NADH in enzyme-catalyzed reactions such as those found in the glycolytic pathway of yeast. In this paper we describe the use of light sensors (photodiodes) in each well to measure both fluorescence (such as that evidenced in NADH) as well as bioluminescence (such as evidenced in ATP assays). We show that our detection limit for NADH fluorescence in 100 μM and for ATP/luciferase bioluminescence is 2.4 μM.

  18. High Field Optomagnetic (OM) Polarization-Phase Selective (PPS) Monitoring of Structures and Controlling Reaction Agents Mechanisms in Complex Molecular Systems

    NASA Astrophysics Data System (ADS)

    Rupnik, Kresimir

    2014-03-01

    Using OM techniques, including new high filed 25T Split-Florida magnet at NHMF Laboratory, we have recently observed unusual metal cluster structures and electron transfer patterns in complex molecular systems of biomedical and material science interest. We report here some of the new technological solutions and (many) challenges that face OM and (quantum) control research. Of particular interest is identification of fast (10-100s fs) highly correlated electrons spin and vibrational coupling interpreted using adaptive molecular-photonic interaction models. Our observations question interpretations of previously proposed electron spin structure models and mechanisms and\\ indicate possible new controlling mechanisms through highly selective coupled channels that combine different specific redox and photonic agents. A portion of this work from 2008 to 2013 was performed at the National High Magnetic Field Laboratory, which is supported by National Science Foundation Cooperative Agreement No. DMR-1157490, and 0654118 and the U.S. Department of Energy.

  19. Identification of known chemicals and their metabolites from Alpinia oxyphylla fruit extract in rat plasma using liquid chromatography/tandem mass spectrometry (LC-MS/MS) with selected reaction monitoring.

    PubMed

    Chen, Feng; Li, Hai-Long; Tan, Yin-Feng; Li, Yong-Hui; Lai, Wei-Yong; Guan, Wei-Wei; Zhang, Jun-Qing; Zhao, Yuan-Sheng; Qin, Zhen-Miao

    2014-08-01

    Alpinia oxyphylla (Yizhi) capsularfruits are commonly used in traditional medicine. Pharmacological studies have demonstrated that A. oxyphylla capsularfruits have some beneficial roles. Besides volatile oil, sesquiterpenes, diarylheptanoids and flavonoids are main bioactive constituents occurring in the Yizhi capsularfruits. The representative constituents include tectochrysin, izalpinin, chrysin, apigenin-4',7-dimethylether, kaempferide, yakuchinone A, yakuchinone B, oxyphyllacinol and nootkatone. Their content levels in the fruit and its pharmaceutical preparations have been reported by our group. The nine phytochemicals are also the major components present in the Yizhi alcoholic extracts, which have anti-diarrheal activities. However, the fates of these constituents in the body after oral or intravenous administration remain largely unknown. In the present study, we focus on these phytochemicals albeit other concomitant compounds. The chemicals and their metabolites in rat plasma were identified using liquid chromatography/tandem mass spectrometry with selected reaction monitoring mode after orally administered Yizhi extract to rats. Rat plasma samples were treated by methanol precipitation, acidic or enzymatic hydrolysis. This target analysis study revealed that: (1) low or trace plasma levels of parent chemicals were measured after p.o. administration of Yizhi extract, Suoquan capsules and pills to rats; (2) flavonoids and diarylheptanoids formed mainly monoglucuronide metabolites; however, diglucuronide metabolites for chrysin, izalpinin and kaempferide were also detected; (3) metabolic reduction of Yizhi diarylheptanoids occurred in rats. Yakuchinone B was reduced to yakuchinone A and then to oxyphyllacinol in a stepwise manner and subsequently glucuronidated by UDP-glucuronosyl transferase. Further research is needed to characterize the UDP-glucuronosyl transferase and reductase involved in the biotransformation of Yizhi chemicals. PMID:24879483

  20. A Generalized Selection Rule for Pericyclic Reactions.

    ERIC Educational Resources Information Center

    He, Fu-Cheng; Pfeiffer, Gary V.

    1984-01-01

    Describes a convenient procedure, the Odd-Even Rule, for predicting the allowedness of forbiddenness of ground-state, pericyclic reactions. The rule is applied to a number of specific reactions. In contrast to the Woodward-Hoffman approach, the application to each reaction is always the same. (JN)

  1. State- and bond-selected unimolecular reactions

    SciTech Connect

    Crim, F.F. )

    1990-09-21

    Unimolecular reactions are crucial chemical events that have been the focus of increasingly sophisticated investigation in the past decade. Unraveling their details is one fundamental goal of experimental and theoretical studies of chemical dynamics. New techniques are revealing the possibilities, and challenges, of eigenstate- and bond-specific unimolecular reactions. These experiments clearly demonstrate the intimate connection between intramolecular processes and unimolecular reaction dynamics and suggest means of exploiting molecular properties to study and control reactions at the level of individual quantum states. 55 refs., 3 figs.

  2. Diagnostic reasoning techniques for selective monitoring

    NASA Technical Reports Server (NTRS)

    Homem-De-mello, L. S.; Doyle, R. J.

    1991-01-01

    An architecture for using diagnostic reasoning techniques in selective monitoring is presented. Given the sensor readings and a model of the physical system, a number of assertions are generated and expressed as Boolean equations. The resulting system of Boolean equations is solved symbolically. Using a priori probabilities of component failure and Bayes' rule, revised probabilities of failure can be computed. These will indicate what components have failed or are the most likely to have failed. This approach is suitable for systems that are well understood and for which the correctness of the assertions can be guaranteed. Also, the system must be such that changes are slow enough to allow the computation.

  3. COPD Exacerbation Biomarkers Validated Using Multiple Reaction Monitoring Mass Spectrometry

    PubMed Central

    Leung, Janice M.; Chen, Virginia; Hollander, Zsuzsanna; Dai, Darlene; Tebbutt, Scott J.; Aaron, Shawn D.; Vandemheen, Kathy L.; Rennard, Stephen I.; FitzGerald, J. Mark; Woodruff, Prescott G.; Lazarus, Stephen C.; Connett, John E.; Coxson, Harvey O.; Miller, Bruce; Borchers, Christoph; McManus, Bruce M.; Ng, Raymond T.; Sin, Don D.

    2016-01-01

    Background Acute exacerbations of chronic obstructive pulmonary disease (AECOPD) result in considerable morbidity and mortality. However, there are no objective biomarkers to diagnose AECOPD. Methods We used multiple reaction monitoring mass spectrometry to quantify 129 distinct proteins in plasma samples from patients with COPD. This analytical approach was first performed in a biomarker cohort of patients hospitalized with AECOPD (Cohort A, n = 72). Proteins differentially expressed between AECOPD and convalescent states were chosen using a false discovery rate <0.01 and fold change >1.2. Protein selection and classifier building were performed using an elastic net logistic regression model. The performance of the biomarker panel was then tested in two independent AECOPD cohorts (Cohort B, n = 37, and Cohort C, n = 109) using leave-pair-out cross-validation methods. Results Five proteins were identified distinguishing AECOPD and convalescent states in Cohort A. Biomarker scores derived from this model were significantly higher during AECOPD than in the convalescent state in the discovery cohort (p<0.001). The receiver operating characteristic cross-validation area under the curve (CV-AUC) statistic was 0.73 in Cohort A, while in the replication cohorts the CV-AUC was 0.77 for Cohort B and 0.79 for Cohort C. Conclusions A panel of five biomarkers shows promise in distinguishing AECOPD from convalescence and may provide the basis for a clinical blood test to diagnose AECOPD. Further validation in larger cohorts is necessary for future clinical translation. PMID:27525416

  4. Monitoring reactions for the calibration of relativistic hadron beams

    NASA Astrophysics Data System (ADS)

    Ferrari, A.; La Torre, F. P.; Manessi, G. P.; Pozzi, F.; Silari, M.

    2014-11-01

    The well-known foil activation technique was used to calibrate an ionisation chamber employed for the on-line beam monitoring of a 120 GeV c-1 mixed proton/pion beam at CERN. Two monitoring reactions were employed: the standard 27Al(p,3pn)24Na and the alternative natCu(p,x)24Na. The parameters on which the technique critically depends and the adopted solutions are thoroughly analysed are the cross-section, the contribution of the competing reactions to the induced activity and the recoil nuclei effect. The experimental results are compared with FLUKA Monte Carlo simulations and with past results obtained with various calibration techniques. The comparison confirms that both reactions can be effectively employed. The natCu(p,x)24Na reaction shows advantages because its cross-section is known at very high energies with a low uncertainty and the production of 24Na is not affected by competing low energy neutron-induced reactions. The contribution of the competing reactions in the case of the 27Al(p,3pn)24Na reaction has been estimated to be 4.3%/100 mg cm-2, whereas the effect of recoil nuclei is negligible.

  5. CHEMICAL REACTIONS OF AQUATIC HUMIC MATERIALS WITH SELECTED OXIDANTS

    EPA Science Inventory

    A study was conducted to identify the specific organic reaction products of natural aquatic humic materials with selected oxidants (KMnO4, HOCl, Cl02, O3 and monochloramine). Reaction products were identified by GC/MS after solvent extraction and derivatization. The two most reac...

  6. Online monitoring of chemical reactions by polarization-induced electrospray ionization.

    PubMed

    Meher, Anil Kumar; Chen, Yu-Chie

    2016-09-21

    Polarization-induced electrospray ionization (PI-ESI) is a simple technique for instant generation of gas-phase ions directly from a microliter-sized droplet for mass spectrometric analysis. A sample droplet was placed over a dielectric substrate and in proximity (2-3 mm) to the inlet of a mass spectrometer. Owing to the polarization effect induced by the high electric field provided by the mass spectrometer, the droplet was polarized and the electrospray was generated from the apex of the droplet. The polarization-induced electrospray could last for tens of seconds, which was sufficiently long to monitor fast reactions occurring within few seconds. Thus, we demonstrated the feasibility of using the droplet-based PI-ESI MS for the online monitoring of fast reactions by simply mixing two droplets (5-10 μL) containing reactants on a dielectric substrate placed in front of a mass spectrometer applied with a high voltage (-4500 V). Schiff base reactions and oxidation reactions that can generate intermediates/products within a few seconds were selected as the model reactions. The ionic reaction species generated from intermediates and products can be simultaneously monitored by PI-ESI MS in real time. We also used this approach to selectively detect acetone from a urine sample, in which acetone was derivatized in situ. In addition, the possibility of using this approach for quantitative analysis of acetone from urine samples was examined. PMID:27590551

  7. Psychological Reactions Associated With Continuous Glucose Monitoring in Youth.

    PubMed

    Patton, Susana R; Clements, Mark A

    2016-05-01

    Glucose monitoring is prerequisite to all other diabetes self-care behaviors and helps patients to reduce their risk for diabetes-related complications due to elevated glycemia. Because of the amount of information available and the ability to deliver glucose results in real-time, continuous glucose monitoring (CGM) has the ability to improve on self-monitoring blood glucose. However, epidemiologic data demonstrate slow uptake of CGM by patients, especially among youth. Several new diabetes therapies rely on CGM for feedback on patients' glucose levels to optimize treatment (eg, the low-glucose suspend insulin pump) and there are new technologies currently in development that will also need this information to work (eg, the artificial pancreas). To help patients to realize the potential benefits of these new treatments, it is essential to explore patients' psychological and behavioral reactions to CGM and then target device enhancements and/or the development of behavioral therapies to minimize negative reactions and to improve patients' CGM adoption rates. Limited research is available examining the psychological and behavioral reactions of CGM use in youth exclusively, but there are more studies examining these reactions in mixed samples of youth, parents, and adults. The purpose of this review is to summarize the available literature examining psychological and behavioral reactions to CGM use in young people with diabetes and to highlight how the results of past and future studies can inform device updates and/or behavioral intervention development to minimize barriers. PMID:26969141

  8. Automatic, continuous online monitoring of polymerization reactions (ACOMP): Progress in characterization of polymers and polymerization reactions

    NASA Astrophysics Data System (ADS)

    Alb, Alina M.

    An original method is presented as an efficient technique for characterizing polymers, and understanding the kinetics of the polymerization reactions. The Automatic Continuous Online Monitoring of Polymerization Reactions (ACOMP) method developed at Tulane University involves following one or more characteristics of a polymerization reaction: monomer conversion, different molecular weight averages, intrinsic viscosity, etc. By performing an automatic withdrawal and dilution of the polymer solution to create a small stream which flows through a detector train, including light scattering, viscometer, refractive index, Ultraviolet/Visible detectors, a continuum of data points can be obtained, allowing powerful analysis methods to be developed. The goal of this work is to expand ACOMP to new polymerization reactions, such as free radical copolymerization, controlled radical polymerization, inverse emulsion polymerization, both to achieve a complete physical characterization of the polymers synthesized and a better understanding of the reaction mechanisms. For each of the reactions ACOMP brings significant innovations in the analysis of the kinetics. Other new methods, such as Automatic Continuous Mixing (ACM) and Simultaneous Multiple Sample Light Scattering (SMSLS) are also used, as well as traditional multi-detector Size Exclusion Chromatography (SEC). As an immediate consequence it is hoped that the information on reaction kinetics and mechanisms offer a better fundamental knowledge, control and ability to optimize reactions. At the industrial scale, online monitoring should allow a more efficient use of resources, energy, reactor and personnel time as well as a higher product quality.

  9. 21 CFR 812.43 - Selecting investigators and monitors.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Selecting investigators and monitors. 812.43... investigators and monitors. (a) Selecting investigators. A sponsor shall select investigators qualified by... investigational devices only to qualified investigators participating in the investigation. (c)...

  10. State-to-state reaction dynamics: A selective review

    NASA Astrophysics Data System (ADS)

    Teslja, Alexey; Valentini, James J.

    2006-10-01

    A selective review of state-to-state reaction dynamics experiments is presented. The review focuses on three classes of reactions that exemplify the rich history and illustrate the current state of the art in such work. These three reactions are (1) the hydrogen exchange reaction, H +H2→H2+H and its isotopomers; (2) the H +RH→H2+R reactions, where RH is an alkane, beginning with H +CH4→H2+CH3 and extending to much larger alkanes; and (3) the Cl +RH→HCl+R reactions, principally Cl +CH4→HCl+CH3. We describe the experiments, discuss their results, present comparisons with theory, and introduce heuristic models.

  11. Select a continuous emissions monitoring system

    SciTech Connect

    Walker, K.

    1996-02-01

    The Environmental Protection Agency (EPA) is incorporating flexibility in the new regulations it is writing to implement the monitoring requirements of Title VII of the Clean Air Act Amendments of 1990. These requirements are commonly known as compliance assurance monitoring (CAM), which is the new name for enhanced monitoring. The new flexibility being written into the CAM regulations is likely to result in reduced costs for industry and additional headaches for the engineer or manager responsible for implementing CAM. Continuous emissions monitoring systems (CEMS) were once the only choice available for continuous compliance monitoring. The primary monitoring strategies expected to be allowed under the CAM rules include not only CEMS, but also predictive emissions monitoring systems, parametric monitoring, and operation and maintenance recordkeeping. These four methods are discussed and compared.

  12. Mass-spectrometric monitoring of the stress reaction during anesthesia

    NASA Astrophysics Data System (ADS)

    Elizarov, A. Yu.; Levshankov, A. I.; Faizov, I. I.; Shchegolev, A. V.

    2013-10-01

    Clinical testing data for a mass-spectrometric method of estimating the patient's stress reaction to an injury done during anesthesia are presented. The essence of the method is monitoring the respiratory coefficient, which is defined as ratio N of the expiratory mass concentration of CO2 to the inspiratory mass concentration of O2 at each breathing cycle. For on-line monitoring of N, an electron ionization mass spectrometer connected to the breathing circuit of an inhalational anesthesia machine is used. Estimates of the anesthesia adequacy obtained with this method are compared with those obtained with the method that analyzes induced acoustic encephalographic potentials. It is shown that the method suggested is more sensitive to the level of the patient's stress reaction during anesthesia than the induced potential method.

  13. System and process for pulsed multiple reaction monitoring

    DOEpatents

    Belov, Mikhail E

    2013-05-17

    A new pulsed multiple reaction monitoring process and system are disclosed that uses a pulsed ion injection mode for use in conjunction with triple-quadrupole instruments. The pulsed injection mode approach reduces background ion noise at the detector, increases amplitude of the ion signal, and includes a unity duty cycle that provides a significant sensitivity increase for reliable quantitation of proteins/peptides present at attomole levels in highly complex biological mixtures.

  14. Spatially resolved chemical reaction monitoring using magnetic resonance imaging.

    PubMed

    Feindel, Kirk W

    2016-06-01

    Over the previous three decades, the use of MRI for studying dynamic physical and chemical processes of materials systems has grown significantly. This mini-review provides a brief introduction to relevant principles of MRI, including methods of spatial localization, factors contributing to image contrast, and chemical shift imaging. A few historical examples of (1) H MRI for reaction monitoring will be presented, followed by a review of recent research including (1) H MRI studies of gelation and biofilms, (1) H, (7) Li, and (11) B MRI studies of electrochemical systems, in vivo glucose metabolism monitored with (19) F MRI, and in situ temperature monitoring with (27) Al MRI. Copyright © 2015 John Wiley & Sons, Ltd. PMID:25589470

  15. Online monitoring of polymerization reactions in inverse emulsions.

    PubMed

    Alb, Alina M; Farinato, Ray; Calbick, Joe; Reed, Wayne F

    2006-01-17

    Automatic continuous online monitoring of polymerization reactions (ACOMP) was adapted to the monitoring of acrylamide polymerization in inverse emulsions. This is the first application of ACOMP to heterogeneous phase polymerization. The conversion and reduced viscosity were monitored by continuously inverting and diluting the emulsion phase using a small reactor sample stream and a breaker surfactant solution, followed by UV absorption and viscometric detection. This inversion into a stable portion of the polymer/surfactant phase diagram is accomplished in tens of seconds, yielding dilute solutions containing acrylamide (Aam), polyacrylamide (PA), oil droplets, and small quantities of surfactant, initiator and other debris, and low molecular weight compounds. After establishing the means of making ACOMP measurements, a first application of the method is made to resolving some of the kinetic issues involved in emulsion polymerization, including the evolution of molecular mass, and the simultaneous action of an "intrinsic" initiator and an added chemical initiator. PMID:16401138

  16. Parallel Reaction Monitoring: A Targeted Experiment Performed Using High Resolution and High Mass Accuracy Mass Spectrometry

    PubMed Central

    Rauniyar, Navin

    2015-01-01

    The parallel reaction monitoring (PRM) assay has emerged as an alternative method of targeted quantification. The PRM assay is performed in a high resolution and high mass accuracy mode on a mass spectrometer. This review presents the features that make PRM a highly specific and selective method for targeted quantification using quadrupole-Orbitrap hybrid instruments. In addition, this review discusses the label-based and label-free methods of quantification that can be performed with the targeted approach. PMID:26633379

  17. Sensor selection for outdoor air quality monitoring

    NASA Astrophysics Data System (ADS)

    Dorsey, K. L.; Herr, John R.; Pisano, A. P.

    2014-06-01

    Gas chemical monitoring for next-generation robotics applications such as fire fighting, explosive gas detection, ubiquitous urban monitoring, and mine safety require high performance, reliable sensors. In this work, we discuss the performance requirements of fixed-location, mobile vehicle, and personal sensor nodes for outdoor air quality sensing. We characterize and compare the performance of a miniature commercial electrochemical and a metal oxide gas sensor and discuss their suitability for environmental monitoring applications. Metal oxide sensors are highly cross-sensitive to factors that affect chemical adsorption (e.g., air speed, pressure) and require careful enclosure design or compensation methods. In contrast, electrochemical sensors are less susceptible to environmental variations, have very low power consumption, and are well matched for mobile air quality monitoring.

  18. Activity and selectivity of molybdenum catalysts in coal liquefaction reactions

    SciTech Connect

    Curtis, C.W.; Pellegrino, J.L. )

    1988-06-01

    During coal liquefaction, coal fragments forming a liquid product with reduced heteroatom content. Coal can be considered to be a large network of polynuclear aromatic species connected by heteroatoms and alkyl bridging structures. Predominant heteroatoms contained in coal are sulfur, oxygen, and nitrogen. Predominant alkyl bridges are methylene and ethylene structures. The purpose of this work is to evaluate how effectively three different molybdenum catalysts promote reactions involving heteroatom removal and cleavage of alkyl bridge structures. The reactions studied include: hydrogenation (HYD), hydrodeoxygenation (HDO), hydrosulfurization (HDS), hydrodenitrogenation (HDN) and hydrocracking (HYC). Both model and coal liquefaction reactions were performed to test the activity and selectivity of three different molybdenum catalysts. The three catalysts used were molybdenum napththenate, molybdenum supported on gamma alumina (Mo/Al/sub 2/O/sub 3/) and precipitated, poorly crystalline molybdenum disulfide (MoS/sub 2/). The model compounds, chosen to mimic coal structure, on which the effectiveness of the catalysts for the model reactions was tested were: 1-methylnaphthalene, representing aromatic hydrocarbons, for hydrogenation; 1-naphthol, representing oxygen containing compounds, for deoxygenation; benzothiophene, representing sulfur containing compounds, for desulfurization; indole, representing nitrogen containing compounds, for denitrogenation; and bibenzyl, representing alkyl bridging structures, for hydrocracking. Catalytic reactions of combinations of reactants were performed to simulate a complex coal matrix. Thermal and catalytic coal liquefaction reactions were performed using Illinois No. 6 coal with anthracene as a solvent. The efficacy of the catalysts was determined by comparing the product and compound class fractions obtained from the liquefaction reactions.

  19. Activity and selectivity of molybdenum catalysts in coal liquefaction reactions

    SciTech Connect

    Curtis, C.W.; Pellegrino, J.L. )

    1988-01-01

    The purpose of this work is to evaluate how effectively three different molybdenum catalysts promote reactions involving heteroatom removal and cleavage of alkyl bridge hydrodeoxygenation (HDO), hydrodesulfurization (HDS), hydrodenitrogenation (HDN) and hydrocracking (HYC). Both model and coal liquefaction reactions were performed to test the activity and selectivity of three different molybdenum catalysts. The three catalysts used were molybdenum naphthenate, molybdenum supported on gamma alumina (Mo/Al{sub 2}O{sub 3}) and precipitated, poorly crystalline molybdenum disulfide (MoS{sub 2}). The model compounds, chosen to mimic coal structure, on which the effectiveness of the catalysts for the model reactions was tested were: 1-methylnaphthalene, representing aromatic hydrocarbons, for hydrogenation; 1-naphthol, representing oxygen containing compounds, for deoxygenation; benzothiophene, representing sulfur containing compounds, for desulfurization; indole, representing nitrogen containing compounds, for denitrogenation; and bibenzyl, representing alkyl bridging structures, for hydrocracking. Catalytic reactions of combinations of reactants were performed to simulate a complex coal matrix. Thermal and catalytic coal liquefaction reactions were performed using Illinois No. 6 coal with anthracene as a solvent. The efficacy of the catalysts was determined by comparing the product and compound class fractions obtained from the liquefaction reactions.

  20. Selective effects of physical exercise on choice reaction processes.

    PubMed

    Arcelin, R; Delignieres, D; Brisswalter, J

    1998-08-01

    The aim of the present study was to examine the effects of an exercise of moderate intensity (60% of maximal aerobic power) on specific information-processing mechanisms. 22 students completed 3 10-min. exercise bouts on a bicycle ergometer. Concomitantly, participants performed six manual-choice-reaction tasks manipulating task variables (Signal Intensity, Stimulus-Response Compatibility, and Time Uncertainty) on two levels. Reaction tests, randomly ordered, were administered at rest and during exercise. A significant underadditive interaction between Time Uncertainty and exercise was found for the highest quartiles of the distribution of reaction times. No other interaction effects were obtained for the other variables. These results reasonably support that moderate aerobic exercise showed selective rather than general influences on information processing. PMID:9760644

  1. Switchable selectivity in an NHC-catalysed dearomatizing annulation reaction

    NASA Astrophysics Data System (ADS)

    Guo, Chang; Fleige, Mirco; Janssen-Müller, Daniel; Daniliuc, Constantin G.; Glorius, Frank

    2015-10-01

    The development of general catalytic methods for the regio- and stereoselective construction of chiral N-heterocycles in a diversity-oriented fashion remains a formidable challenge in organic synthesis. N-heterocyclic carbene (NHC) catalysis has been shown to produce a variety of outcomes, but control of the reactivity has rarely been demonstrated. Here we report a switchable catalytic activation of enals with aromatic azomethine imines that provides high selectivity using NHC organocatalysts. The original selectivity corresponds to the acidity of the base used in the reaction. The catalytically generated chiral homoenolate or enol intermediate undergoes enantioselective annulation with electrophiles such as N-iminoquinolinium ylides, N-iminoisoquinolinium ylides and β-N-iminocarboline ylides. The good-to-high overall yields, high regioselectivities and excellent enantioselectivities observed are controlled by the catalyst and reaction conditions.

  2. Thermal selectivity of intermolecular versus intramolecular reactions on surfaces

    PubMed Central

    Cirera, Borja; Giménez-Agulló, Nelson; Björk, Jonas; Martínez-Peña, Francisco; Martin-Jimenez, Alberto; Rodriguez-Fernandez, Jonathan; Pizarro, Ana M.; Otero, Roberto; Gallego, José M.; Ballester, Pablo; Galan-Mascaros, José R.; Ecija, David

    2016-01-01

    On-surface synthesis is a promising strategy for engineering heteroatomic covalent nanoarchitectures with prospects in electronics, optoelectronics and photovoltaics. Here we report the thermal tunability of reaction pathways of a molecular precursor in order to select intramolecular versus intermolecular reactions, yielding monomeric or polymeric phthalocyanine derivatives, respectively. Deposition of tetra-aza-porphyrin species bearing ethyl termini on Au(111) held at room temperature results in a close-packed assembly. Upon annealing from room temperature to 275 °C, the molecular precursors undergo a series of covalent reactions via their ethyl termini, giving rise to phthalocyanine tapes. However, deposition of the tetra-aza-porphyrin derivatives on Au(111) held at 300 °C results in the formation and self-assembly of monomeric phthalocyanines. A systematic scanning tunnelling microscopy study of reaction intermediates, combined with density functional calculations, suggests a [2+2] cycloaddition as responsible for the initial linkage between molecular precursors, whereas the monomeric reaction is rationalized as an electrocyclic ring closure. PMID:26964764

  3. Thermal selectivity of intermolecular versus intramolecular reactions on surfaces

    NASA Astrophysics Data System (ADS)

    Cirera, Borja; Giménez-Agulló, Nelson; Björk, Jonas; Martínez-Peña, Francisco; Martin-Jimenez, Alberto; Rodriguez-Fernandez, Jonathan; Pizarro, Ana M.; Otero, Roberto; Gallego, José M.; Ballester, Pablo; Galan-Mascaros, José R.; Ecija, David

    2016-03-01

    On-surface synthesis is a promising strategy for engineering heteroatomic covalent nanoarchitectures with prospects in electronics, optoelectronics and photovoltaics. Here we report the thermal tunability of reaction pathways of a molecular precursor in order to select intramolecular versus intermolecular reactions, yielding monomeric or polymeric phthalocyanine derivatives, respectively. Deposition of tetra-aza-porphyrin species bearing ethyl termini on Au(111) held at room temperature results in a close-packed assembly. Upon annealing from room temperature to 275 °C, the molecular precursors undergo a series of covalent reactions via their ethyl termini, giving rise to phthalocyanine tapes. However, deposition of the tetra-aza-porphyrin derivatives on Au(111) held at 300 °C results in the formation and self-assembly of monomeric phthalocyanines. A systematic scanning tunnelling microscopy study of reaction intermediates, combined with density functional calculations, suggests a [2+2] cycloaddition as responsible for the initial linkage between molecular precursors, whereas the monomeric reaction is rationalized as an electrocyclic ring closure.

  4. Thermal selectivity of intermolecular versus intramolecular reactions on surfaces.

    PubMed

    Cirera, Borja; Giménez-Agulló, Nelson; Björk, Jonas; Martínez-Peña, Francisco; Martin-Jimenez, Alberto; Rodriguez-Fernandez, Jonathan; Pizarro, Ana M; Otero, Roberto; Gallego, José M; Ballester, Pablo; Galan-Mascaros, José R; Ecija, David

    2016-01-01

    On-surface synthesis is a promising strategy for engineering heteroatomic covalent nanoarchitectures with prospects in electronics, optoelectronics and photovoltaics. Here we report the thermal tunability of reaction pathways of a molecular precursor in order to select intramolecular versus intermolecular reactions, yielding monomeric or polymeric phthalocyanine derivatives, respectively. Deposition of tetra-aza-porphyrin species bearing ethyl termini on Au(111) held at room temperature results in a close-packed assembly. Upon annealing from room temperature to 275 °C, the molecular precursors undergo a series of covalent reactions via their ethyl termini, giving rise to phthalocyanine tapes. However, deposition of the tetra-aza-porphyrin derivatives on Au(111) held at 300 °C results in the formation and self-assembly of monomeric phthalocyanines. A systematic scanning tunnelling microscopy study of reaction intermediates, combined with density functional calculations, suggests a [2+2] cycloaddition as responsible for the initial linkage between molecular precursors, whereas the monomeric reaction is rationalized as an electrocyclic ring closure. PMID:26964764

  5. Controlling bimolecular reactions: Mode and bond selected reaction of water with hydrogen atoms

    SciTech Connect

    Sinha, A.; Hsiao, M.C.; Crim, F.F. )

    1991-04-01

    Vibrational overtone excitation prepares water molecules in the {vert bar}13{r angle}{sup {minus}}, {vert bar}04{r angle}{sup {minus}}, {vert bar}12{r angle}{sup {minus}}, {vert bar}02{r angle}{sup {minus}}{vert bar}2{r angle}, and {vert bar}03{r angle}{sup {minus}} local mode states for a study of the influence of reagent vibration on the endothermic bimolecular reaction H+H{sub 2}O{r arrow}OH+H{sub 2}. The reaction of water molecules excited to the {vert bar}04{r angle}{sup {minus}} vibrational state predominantly produces OH({ital v}=0) while reaction from the {vert bar}13{r angle}{sup {minus}} state forms mostly OH({ital v}=1). These results support a spectator model for reaction in which the vibrational excitation of the products directly reflects the nodal pattern of the vibrational wave function in the energized molecule. Relative rate measurements for the three vibrational states {vert bar}03{r angle}{sup {minus}}, {vert bar}02{r angle}{sup {minus}}{vert bar}2{r angle}, and {vert bar}12{r angle}{sup {minus}}, which have similar total energies but correspond to very different distributions of vibrational energy, demonstrate the control that initially selected vibrations exert on reaction rates. The local mode stretching state {vert bar}03{r angle}{sup {minus}} promotes the H+H{sub 2}O reaction much more efficiently than either the state having part of its energy in bending excitation ({vert bar}02{r angle}{sup {minus}}{vert bar}2{r angle}) or the stretching state with the excitation shared between the two O--H oscillators ({vert bar}12{r angle}{sup {minus}}). The localized character of the vibrational overtone excitation in water has permitted the first observation of a bond selected bimolecular reaction using this approach.

  6. Optimal Sensor Selection for Health Monitoring Systems

    NASA Technical Reports Server (NTRS)

    Santi, L. Michael; Sowers, T. Shane; Aguilar, Robert B.

    2005-01-01

    Sensor data are the basis for performance and health assessment of most complex systems. Careful selection and implementation of sensors is critical to enable high fidelity system health assessment. A model-based procedure that systematically selects an optimal sensor suite for overall health assessment of a designated host system is described. This procedure, termed the Systematic Sensor Selection Strategy (S4), was developed at NASA John H. Glenn Research Center in order to enhance design phase planning and preparations for in-space propulsion health management systems (HMS). Information and capabilities required to utilize the S4 approach in support of design phase development of robust health diagnostics are outlined. A merit metric that quantifies diagnostic performance and overall risk reduction potential of individual sensor suites is introduced. The conceptual foundation for this merit metric is presented and the algorithmic organization of the S4 optimization process is described. Representative results from S4 analyses of a boost stage rocket engine previously under development as part of NASA's Next Generation Launch Technology (NGLT) program are presented.

  7. Applications of Multiple Reaction Monitoring to Clinical Glycomics

    PubMed Central

    Ruhaak, L. Renee; Lebrilla, Carlito B.

    2014-01-01

    Multiple reaction monitoring or MRM is widely acknowledged for its accuracy of quantitation. The applications have mostly been in the analysis of small molecules and proteins, but its utility is expanding. Protein glycosylation was recently identified as a new paradigm in biomarker discovery for health and disease. A number of recent studies have now identified differential glycosylation patterns associated with health and disease states, including aging, pregnancy, rheumatoid arthritis and different types of cancer. While the use of MRM in clinical glycomics is still in its infancy, it can likely play a role in the quantitation of protein glycosylation in the clinical setting. Here, we aim to review the current advances in the nascent application of MRM in the field of glycomics. PMID:25892741

  8. Deciphering Selectivity in Organic Reactions: A Multifaceted Problem.

    PubMed

    Balcells, David; Clot, Eric; Eisenstein, Odile; Nova, Ainara; Perrin, Lionel

    2016-05-17

    Computational chemistry has made a sustained contribution to the understanding of chemical reactions. In earlier times, half a century ago, the goal was to distinguish allowed from forbidden reactions (e.g., Woodward-Hoffmann rules), that is, reactions with low or high to very high activation barriers. A great achievement of computational chemistry was also to contribute to the determination of structures with the bonus of proposing a rationalization (e.g., anomeric effect, isolobal analogy, Gillespie valence shell pair electron repulsion rules and counter examples, Wade-Mingos rules for molecular clusters). With the development of new methods and the constant increase in computing power, computational chemists move to more challenging problems, close to the daily concerns of the experimental chemists, in determining the factors that make a reaction both efficient and selective: a key issue in organic synthesis. For this purpose, experimental chemists use advanced synthetic and analytical techniques to which computational chemists added other ways of determining reaction pathways. The transition states and intermediates contributing to the transformation of reactants into the desired and undesired products can now be determined, including their geometries, energies, charges, spin densities, spectroscopy properties, etc. Such studies remain challenging due to the large number of chemical species commonly present in the reactive media whose role may have to be determined. Calculating chemical systems as they are in the experiment is not always possible, bringing its own share of complexity through the large number of atoms and the associated large number of conformers to consider. Modeling the chemical species with smaller systems is an alternative that historically led to artifacts. Another important topic is the choice of the computational method. While DFT is widely used, the vast diversity of functionals available is both an opportunity and a challenge. Though

  9. Warmth and legitimacy beliefs contextualize adolescents' negative reactions to parental monitoring.

    PubMed

    LaFleur, Laura K; Zhao, Yinan; Zeringue, Megan M; Laird, Robert D

    2016-08-01

    This study sought to identify conditions under which parents' monitoring behaviors are most strongly linked to adolescents' negative reactions (i.e., feelings of being controlled and invaded). 242 adolescents (49.2% male; M age = 15.4 years) residing in the United States of America reported parental monitoring and warmth, and their own feelings of being controlled and invaded and beliefs in the legitimacy of parental authority. Analyses tested whether warmth and legitimacy beliefs moderate and/or suppress the link between parents' monitoring behaviors and adolescents' negative reactions. Monitoring was associated with more negative reactions, controlling for legitimacy beliefs and warmth. More monitoring was associated with more negative reactions only at weaker levels of legitimacy beliefs, and at lower levels of warmth. The link between monitoring and negative reactions is sensitive to the context within which monitoring occurs with the strongest negative reactions found in contexts characterized by low warmth and weak legitimacy beliefs. PMID:27310724

  10. Reaction monitoring using online vs tube NMR spectroscopy: seriously different results.

    PubMed

    Foley, David A; Dunn, Anna L; Zell, Mark T

    2016-06-01

    We report findings from the qualitative evaluation of nuclear magnetic resonance (NMR) reaction monitoring techniques of how each relates to the kinetic profile of a reaction process. The study highlights key reaction rate differences observed between the various NMR reaction monitoring methods investigated: online NMR, static NMR tubes, and periodic inversion of NMR tubes. The analysis of three reaction processes reveals that rates derived from NMR analysis are highly dependent on monitoring method. These findings indicate that users must be aware of the effect of their monitoring method upon the kinetic rate data derived from NMR analysis. Copyright © 2015 John Wiley & Sons, Ltd. PMID:26248898

  11. Site-Selective Reactions with Peptide-Based Catalysts.

    PubMed

    Giuliano, Michael W; Miller, Scott J

    2016-01-01

    The problem of catalyst-controlled site-selectivity can potentially require a catalyst to overcome energetic barriers larger than those associated with enantioselective reactions. This challenge is a signature of substrates that present reactive sites that are not of equivalent reactivity. Herein we present a narrative of our laboratory's efforts to overcome this challenge using peptide-based catalysts. We highlight the interplay between understanding the inherent reactivity preferences of a given target molecule and the development of catalysts that can overcome intrinsic preferences embedded within a substrate. PMID:26307403

  12. Copper-catalysed selective hydroamination reactions of alkynes

    NASA Astrophysics Data System (ADS)

    Shi, Shi-Liang; Buchwald, Stephen L.

    2015-01-01

    The development of selective reactions that utilize easily available and abundant precursors for the efficient synthesis of amines is a long-standing goal of chemical research. Despite the centrality of amines in a number of important research areas, including medicinal chemistry, total synthesis and materials science, a general, selective and step-efficient synthesis of amines is still needed. Here, we describe a set of mild catalytic conditions utilizing a single copper-based catalyst that enables the direct preparation of three distinct and important amine classes (enamines, α-chiral branched alkylamines and linear alkylamines) from readily available alkyne starting materials with high levels of chemo-, regio- and stereoselectivity. This methodology was applied to the asymmetric synthesis of rivastigmine and the formal synthesis of several other pharmaceutical agents, including duloxetine, atomoxetine, fluoxetine and tolterodine.

  13. Copper-catalysed selective hydroamination reactions of alkynes.

    PubMed

    Shi, Shi-Liang; Buchwald, Stephen L

    2015-01-01

    The development of selective reactions that utilize easily available and abundant precursors for the efficient synthesis of amines is a long-standing goal of chemical research. Despite the centrality of amines in a number of important research areas, including medicinal chemistry, total synthesis and materials science, a general, selective and step-efficient synthesis of amines is still needed. Here, we describe a set of mild catalytic conditions utilizing a single copper-based catalyst that enables the direct preparation of three distinct and important amine classes (enamines, α-chiral branched alkylamines and linear alkylamines) from readily available alkyne starting materials with high levels of chemo-, regio- and stereoselectivity. This methodology was applied to the asymmetric synthesis of rivastigmine and the formal synthesis of several other pharmaceutical agents, including duloxetine, atomoxetine, fluoxetine and tolterodine. PMID:25515888

  14. Copper-catalyzed selective hydroamination reactions of alkynes

    PubMed Central

    Shi, Shi-Liang; Buchwald, Stephen L.

    2014-01-01

    The development of selective reactions that utilize easily available and abundant precursors for the efficient synthesis of amines is a longstanding goal of chemical research. Despite the centrality of amines in a number of important research areas, including medicinal chemistry, total synthesis and materials science, a general, selective, and step-efficient synthesis of amines is still needed. In this work we describe a set of mild catalytic conditions utilizing a single copper-based catalyst that enables the direct preparation of three distinct and important amine classes (enamines, α-chiral branched alkylamines, and linear alkylamines) from readily available alkyne starting materials with high levels of chemo-, regio-, and stereoselectivity. This methodology was applied to the asymmetric synthesis of rivastigmine and the formal synthesis of several other pharmaceutical agents, including duloxetine, atomoxetine, fluoxetine, and tolterodine. PMID:25515888

  15. Still shimming or already measuring? - Quantitative reaction monitoring for small molecules on the sub minute timescale by NMR

    NASA Astrophysics Data System (ADS)

    Kind, J.; Thiele, C. M.

    2015-11-01

    In order to enable monitoring of rapidly occurring reactions Wagner et al. recently presented a simple scheme for 1D NMR experiments with continuous data acquisition, without inter-scan delays, using a spatially-selective and frequency-shifted excitation approach (Wagner et al., 2013). This scheme allows acquisition of proton spectra with temporal resolutions on the millisecond timescale. Such high temporal resolutions are desired in the case of reaction monitoring using stopped flow setups. In regular 1H NMR-spectra without spatial selection the line width increases for a given shim setting with changes in sample volume, susceptibility, convection and temperature or concentration gradients due to the disturbance of magnetic field homogeneity. Concerning reaction monitoring this is unfortunate as shimming prior to acquisition becomes necessary to obtain narrow signals after injection of a reactant into an NMR sample. Even automatic shim routines may last up to minutes. Thus fast reactions can hardly be monitored online without large hardware dead times in a single stopped flow experiment. This problem is reduced in the spatially-selective and frequency-shifted continuous NMR experiment as magnetic field inhomogeneties are less pronounced and negative effects on the obtained line shapes are reduced as pointed out by Bax and Freeman (1980) [2] and demonstrated by Wagner et al. (2013). Here we present the utilization of this technique for observation of reactions in small molecule systems in which chemical conversion and longitudinal relaxation occur on the same timescale. By means of the alkaline ethyl acetate hydrolysis, a stoichiometric reaction, we show advantages of spatially-selective excitation on both temporal resolution and line shapes in stopped flow experiments. Results are compared to data obtained by non-selective small angle excitation experiments.

  16. Tuning selectivity of electrochemical reactions by atomically dispersed platinum catalyst

    PubMed Central

    Choi, Chang Hyuck; Kim, Minho; Kwon, Han Chang; Cho, Sung June; Yun, Seongho; Kim, Hee-Tak; Mayrhofer, Karl J. J.; Kim, Hyungjun; Choi, Minkee

    2016-01-01

    Maximum atom efficiency as well as distinct chemoselectivity is expected for electrocatalysis on atomically dispersed (or single site) metal centres, but its realization remains challenging so far, because carbon, as the most widely used electrocatalyst support, cannot effectively stabilize them. Here we report that a sulfur-doped zeolite-templated carbon, simultaneously exhibiting large sulfur content (17 wt% S), as well as a unique carbon structure (that is, highly curved three-dimensional networks of graphene nanoribbons), can stabilize a relatively high loading of platinum (5 wt%) in the form of highly dispersed species including site isolated atoms. In the oxygen reduction reaction, this catalyst does not follow a conventional four-electron pathway producing H2O, but selectively produces H2O2 even over extended times without significant degradation of the activity. Thus, this approach constitutes a potentially promising route for producing important fine chemical H2O2, and also offers opportunities for tuning the selectivity of other electrochemical reactions on various metal catalysts. PMID:26952517

  17. Tuning selectivity of electrochemical reactions by atomically dispersed platinum catalyst

    NASA Astrophysics Data System (ADS)

    Choi, Chang Hyuck; Kim, Minho; Kwon, Han Chang; Cho, Sung June; Yun, Seongho; Kim, Hee-Tak; Mayrhofer, Karl J. J.; Kim, Hyungjun; Choi, Minkee

    2016-03-01

    Maximum atom efficiency as well as distinct chemoselectivity is expected for electrocatalysis on atomically dispersed (or single site) metal centres, but its realization remains challenging so far, because carbon, as the most widely used electrocatalyst support, cannot effectively stabilize them. Here we report that a sulfur-doped zeolite-templated carbon, simultaneously exhibiting large sulfur content (17 wt% S), as well as a unique carbon structure (that is, highly curved three-dimensional networks of graphene nanoribbons), can stabilize a relatively high loading of platinum (5 wt%) in the form of highly dispersed species including site isolated atoms. In the oxygen reduction reaction, this catalyst does not follow a conventional four-electron pathway producing H2O, but selectively produces H2O2 even over extended times without significant degradation of the activity. Thus, this approach constitutes a potentially promising route for producing important fine chemical H2O2, and also offers opportunities for tuning the selectivity of other electrochemical reactions on various metal catalysts.

  18. Large-Scale Targeted Proteomics Using Internal Standard Triggered-Parallel Reaction Monitoring (IS-PRM)*

    PubMed Central

    Gallien, Sebastien; Kim, Sang Yoon; Domon, Bruno

    2015-01-01

    Targeted high-resolution and accurate mass analyses performed on fast sequencing mass spectrometers have opened new avenues for quantitative proteomics. More specifically, parallel reaction monitoring (PRM) implemented on quadrupole-orbitrap instruments exhibits exquisite selectivity to discriminate interferences from analytes. Furthermore, the instrument trapping capability enhances the sensitivity of the measurements. The PRM technique, applied to the analysis of limited peptide sets (typically 50 peptides or less) in a complex matrix, resulted in an improved detection and quantification performance as compared with the reference method of selected reaction monitoring performed on triple quadrupole instruments. However, the implementation of PRM for the analysis of large peptide numbers requires the adjustment of mass spectrometry acquisition parameters, which affects dramatically the quality of the generated data, and thus the overall output of an experiment. A newly designed data acquisition scheme enabled the analysis of moderate-to-large peptide numbers while retaining a high performance level. This new method, called internal standard triggered-parallel reaction monitoring (IS-PRM), relies on added internal standards and the on-the-fly adjustment of acquisition parameters to drive in real-time measurement of endogenous peptides. The acquisition time management was designed to maximize the effective time devoted to measure the analytes in a time-scheduled targeted experiment. The data acquisition scheme alternates between two PRM modes: a fast low-resolution “watch mode” and a “quantitative mode” using optimized parameters ensuring data quality. The IS-PRM method exhibited a highly effective use of the instrument time. Applied to the analysis of large peptide sets (up to 600) in complex samples, the method showed an unprecedented combination of scale and analytical performance, with limits of quantification in the low amol range. The successful

  19. Hypersensitivity Reactions to Nonsteroidal Anti-inflammatory Drugs in Children and Adolescents: Selective Reactions.

    PubMed

    Blanca-López, N; Cornejo-García, J A; Pérez-Alzate, D; Pérez-Sánchez, N; Plaza-Serón, M C; Doña, I; Torres, M J; Canto, G; Kidon, M; Perkins, J R; Blanca, M

    2015-01-01

    Nonsteroidal anti-inflammatory drugs (NSAIDs) are used throughout the world to treat pain and inflammation; however, they can trigger several types of drug hypersensitivity reactions (DHRs) in all age groups. Although most such reactions occur through activation of the leukotriene pathway without specific immunological recognition (cross-intolerance), a significant number of DHRs to NSAIDs are due to immunological mechanisms (selective reactions [SRs]). SRs are thought to be induced by specific IgE antibodies or by T cells. In this manuscript, we focus on SRs, which are of great concern in children and adolescents and comprise a heterogeneous set of clinical pictures ranging from mild entities such as urticaria/angioedema to potentially life-threatening conditions such as Stevens-Johnson syndrome/toxic epidermal necrolysis. Paracetamol and ibuprofen are the most frequent elicitors of IgE-mediated SRs, although pyrazolones have also been implicated. T cell-mediated reactions are infrequent in children but have been associated with ibuprofen, naproxen, and dipyrone. In this review, we analyze the available literature on SRs in children and adolescents, with emphasis on epidemiological data, mechanisms, and drugs involved, as well as on diagnostic procedures. PMID:26817135

  20. Spin-selective recombination reactions of radical pairs: Experimental test of validity of reaction operators

    SciTech Connect

    Maeda, Kiminori; Liddell, Paul; Gust, Devens; Hore, P. J.

    2013-12-21

    Spin-selective reactions of radical pairs are conventionally modelled using an approach that dates back to the 1970s [R. Haberkorn, Mol. Phys. 32, 1491 (1976)]. An alternative approach based on the theory of quantum measurements has recently been suggested [J. A. Jones and P. J. Hore, Chem. Phys. Lett. 488, 90 (2010)]. We present here the first experimental attempt to discriminate between the two models. Pulsed electron paramagnetic resonance spectroscopy has been used to investigate intramolecular electron transfer in the radical pair form of a carotenoid-porphyrin-fullerene molecular triad. The rate of spin-spin relaxation of the fullerene radical in the triad was found to be inconsistent with the quantum measurement description of the spin-selective kinetics, and in accord with the conventional model when combined with spin-dephasing caused by rotational modulation of the anisotropic g-tensor of the fullerene radical.

  1. Multichannel quench-flow microreactor chip for parallel reaction monitoring.

    PubMed

    Bula, Wojciech P; Verboom, Willem; Reinhoudt, David N; Gardeniers, Han J G E

    2007-12-01

    This paper describes a multichannel silicon-glass microreactor which has been utilized to investigate the kinetics of a Knoevenagel condensation reaction under different reaction conditions. The reaction is performed on the chip in four parallel channels under identical conditions but with different residence times. A special topology of the reaction coils overcomes the common problem arising from the difference in pressure drop of parallel channels having different length. The parallelization of reaction coils combined with chemical quenching at specific locations results in a considerable reduction in experimental effort and cost. The system was tested and showed good reproducibility in flow properties and reaction kinetic data generation. PMID:18030392

  2. 21 CFR 312.53 - Selecting investigators and monitors.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... investigational purposes and will ensure that the requirements relating to obtaining informed consent (21 CFR part 50) and institutional review board review and approval (21 CFR part 56) are met; (e) Will report to... 21 Food and Drugs 5 2010-04-01 2010-04-01 false Selecting investigators and monitors....

  3. Monitorizing nitinol alloy surface reactions for biofouling studies

    NASA Astrophysics Data System (ADS)

    Dinu, C. Z.; Dinca, V. C.; Soare, S.; Moldovan, A.; Smarandache, D.; Scarisoareanu, N.; Barbalat, A.; Birjega, R.; Dinescu, M.; DiStefano, V. Ferrari

    2007-07-01

    Growth and deposition of unwanted bacteria on implant metal alloys affect their use as biomedical samples. Monitoring any bacterial biofilm accumulation will provide early countermeasures. For a reliable antifouling strategy we prepared nitinol (NiTi) thin films on Ti-derived substrates by using a pulsed laser deposition (PLD) method. As the microstructure of Ti-alloy is dictated by the tensile strength, fatigue and the fracture toughness we tested the use of hydrogen as an alloying element. X-ray diffraction (XRD), scanning electron microscopy (SEM) and atomic force microscopy (AFM) investigated the crystalline structure, chemical composition and respectively the surface morphology of the nitinol hydrogen and hydrogen-free samples. Moreover, the alloys were integrated and tested using a cellular metric and their responses were systematic evaluated and quantified. Our attractive approach is meant to select the suitable components for an effective and trustworthy anti-fouling strategy. A greater understanding of such processes should lead to novel and effective control methods that would improve in the future implant stability and capabilities.

  4. Early Identification of Acute Hemolytic Transfusion Reactions: Realistic Implications for Best Practice in Patient Monitoring.

    PubMed

    Menendez, Juliet Battard; Edwards, Barbara

    2016-01-01

    Acute hemolytic transfusion reactions can result in severe complications and death. Through early identification and prompt intervention, nurses can reduce the risks associated with these serious reactions. Realistic evidence-based patient monitoring protocols can help guide identification of acute hemolytic transfusion reactions and facilitate lifesaving interventions to avert critical patient situations. PMID:27323466

  5. Targeted Quantitative Analysis of Streptococcus pyogenes Virulence Factors by Multiple Reaction Monitoring*S⃞

    PubMed Central

    Lange, Vinzenz; Malmström, Johan A.; Didion, John; King, Nichole L.; Johansson, Björn P.; Schäfer, Juliane; Rameseder, Jonathan; Wong, Chee-Hong; Deutsch, Eric W.; Brusniak, Mi-Youn; Bühlmann, Peter; Björck, Lars; Domon, Bruno; Aebersold, Ruedi

    2008-01-01

    In many studies, particularly in the field of systems biology, it is essential that identical protein sets are precisely quantified in multiple samples such as those representing differentially perturbed cell states. The high degree of reproducibility required for such experiments has not been achieved by classical mass spectrometry-based proteomics methods. In this study we describe the implementation of a targeted quantitative approach by which predetermined protein sets are first identified and subsequently quantified at high sensitivity reliably in multiple samples. This approach consists of three steps. First, the proteome is extensively mapped out by multidimensional fractionation and tandem mass spectrometry, and the data generated are assembled in the PeptideAtlas database. Second, based on this proteome map, peptides uniquely identifying the proteins of interest, proteotypic peptides, are selected, and multiple reaction monitoring (MRM) transitions are established and validated by MS2 spectrum acquisition. This process of peptide selection, transition selection, and validation is supported by a suite of software tools, TIQAM (Targeted Identification for Quantitative Analysis by MRM), described in this study. Third, the selected target protein set is quantified in multiple samples by MRM. Applying this approach we were able to reliably quantify low abundance virulence factors from cultures of the human pathogen Streptococcus pyogenes exposed to increasing amounts of plasma. The resulting quantitative protein patterns enabled us to clearly define the subset of virulence proteins that is regulated upon plasma exposure. PMID:18408245

  6. Meat Authentication via Multiple Reaction Monitoring Mass Spectrometry of Myoglobin Peptides.

    PubMed

    Watson, Andrew D; Gunning, Yvonne; Rigby, Neil M; Philo, Mark; Kemsley, E Kate

    2015-10-20

    A rapid multiple reaction monitoring (MRM) mass spectrometric method for the detection and relative quantitation of the adulteration of meat with that of an undeclared species is presented. Our approach uses corresponding proteins from the different species under investigation and corresponding peptides from those proteins, or CPCP. Selected peptide markers can be used for species detection. The use of ratios of MRM transition peak areas for corresponding peptides is proposed for relative quantitation. The approach is introduced by use of myoglobin from four meats: beef, pork, horse and lamb. Focusing in the present work on species identification, by use of predictive tools, we determine peptide markers that allow the identification of all four meats and detection of one meat added to another at levels of 1% (w/w). Candidate corresponding peptide pairs to be used for the relative quantification of one meat added to another have been observed. Preliminary quantitation data presented here are encouraging. PMID:26366801

  7. Model Selection for Monitoring CO2 Plume during Sequestration

    SciTech Connect

    2014-12-31

    The model selection method developed as part of this project mainly includes four steps: (1) assessing the connectivity/dynamic characteristics of a large prior ensemble of models, (2) model clustering using multidimensional scaling coupled with k-mean clustering, (3) model selection using the Bayes' rule in the reduced model space, (4) model expansion using iterative resampling of the posterior models. The fourth step expresses one of the advantages of the method: it provides a built-in means of quantifying the uncertainty in predictions made with the selected models. In our application to plume monitoring, by expanding the posterior space of models, the final ensemble of representations of geological model can be used to assess the uncertainty in predicting the future displacement of the CO2 plume. The software implementation of this approach is attached here.

  8. Model Selection for Monitoring CO2 Plume during Sequestration

    Energy Science and Technology Software Center (ESTSC)

    2014-12-31

    The model selection method developed as part of this project mainly includes four steps: (1) assessing the connectivity/dynamic characteristics of a large prior ensemble of models, (2) model clustering using multidimensional scaling coupled with k-mean clustering, (3) model selection using the Bayes' rule in the reduced model space, (4) model expansion using iterative resampling of the posterior models. The fourth step expresses one of the advantages of the method: it provides a built-in means ofmore » quantifying the uncertainty in predictions made with the selected models. In our application to plume monitoring, by expanding the posterior space of models, the final ensemble of representations of geological model can be used to assess the uncertainty in predicting the future displacement of the CO2 plume. The software implementation of this approach is attached here.« less

  9. Monitoring biochemical reactions using Y-cut quartz thermal sensors.

    PubMed

    Ren, Kailiang; Kao, Ping; Pisani, Marcelo B; Tadigadapa, Srinivas

    2011-07-21

    In this paper, we present a micromachined Y-cut quartz resonator based thermal sensor array which is configured with a reaction chamber that is physically separated but located in close proximity to the resonator for sensitive calorimetric biosensing applications. The coupling of heat from the reaction chamber to the quartz resonator is achieved via radiation and conduction through ambient gas. The sensor was packaged onto a 300 μm thick stainless plate with an opening in the middle. The sensor array was aligned to the opening and mounted from the underside of the plate. A reaction chamber designed for performing (bio)chemical reactions was used in the measurements. This configuration of the sensor allows for a very robust sensing platform with no fouling of the sensor surface or degradation in its performance metrics. Impedance-based tracking of resonance frequency was used for chemical, enzymatic, and cellular activity measurements. The sensor described has an impedance sensitivity of 852 Ω °C(-1) or a frequency sensitivity of 7.32 kHz °C(-1) for the 91 MHz resonator used in this work. Results on exothermic reaction between hydrochloric acid and ammonium hydroxide, the hydrolysis reaction of urea by urease and the catalytic reaction of glucose with glucose dehydrogenase are reported. From the signal to noise ratio analysis of the glucose sensor, <10 μM glucose sensitivity could be obtained improving the detection limit by a factor of 250 in comparison to our previous work using thermopile sensors. Finally, calcium ionophore induced cellular activity was measured in pancreatic cancer cells using the sensor. PMID:21655628

  10. Rheological monitoring of phase separation induced by chemical reaction in thermoplastic-modified epoxy

    SciTech Connect

    Vinh-Tung, C.; Lachenal, G.; Chabert, B.

    1996-12-31

    The phase separation induced by chemical reaction in blends of tetraglycidyl-diaminodiphenylmethane epoxy resin with an aromatic diamine hardener and a thermoplastic was monitored. Rheological measurements and morphologies are described.

  11. Monitoring Of Landslide Hazard In Selected Areas Of Uzbekistan

    NASA Astrophysics Data System (ADS)

    Lazecky, Milan; Balaha, Pavel; Khasankhanova, Gulchekhra; Minchenko, Venscelas

    2013-12-01

    Republic of Uzbekistan is situated in the heart of Central Asia. Dangerous phenomena such as drought, flooding, mud flows, landslides and others, that are becoming frequent in conditions of climate changes, increase instability of an agricultural production, and threaten rural livelihoods. In connection with weather and climate natural disasters, these phenomena become reasons of declining food production, water contamination, and economical damages. Within the Project granted by NATO: Science for Peace and Security programme, modern advanced remote sensing technologies will be applied to perform large scale monitoring of (early) slope deformations, including Satellite SAR Interferometry (InSAR) techniques, Ground Laser Scanning for in-situ refinement of detected movements or Multibeam Echosounding for monitoring slope deformation advancement into water objects. First results involving InSAR processing of selected sites in Uzbekistan are presented within this contribution.

  12. Esterification Reaction Utilizing Sense of Smell and Eyesight for Conversion and Catalyst Recovery Monitoring

    ERIC Educational Resources Information Center

    Janssens, Nikki; Wee, Lik H.; Martens, Johan A.

    2014-01-01

    The esterification reaction of salicylic acid with ethanol is performed in presence of dissolved 12-tungstophosphoric Brønsted-Lowry acid catalyst, a Keggin-type polyoxometalate (POM). The monitoring of the reaction with smell and the recovery of the catalyst with sight is presented. Formation of the sweet-scented ester is apparent from the smell.…

  13. How to select a continuous emission monitoring system

    SciTech Connect

    Radigan, M.J. )

    1994-02-01

    Selecting a continuous emission monitoring system (CEMS) involves more than picking an analyzer. Successful CEMS interface sampling and data-management systems to produce accurate, reliable reports required by regulatory agencies. Following objective guidelines removes some of the misery from CEMS shopping. However, prospective CEMS buyers should do their homework and develop well-thought-out, detailed specification for the processes' sampling criteria. Fine tuning the analyzer/data management system can eliminate maintenance costs and keep the facility operating within its permit restrictions.

  14. Strategy Developed for Selecting Optimal Sensors for Monitoring Engine Health

    NASA Technical Reports Server (NTRS)

    2004-01-01

    Sensor indications during rocket engine operation are the primary means of assessing engine performance and health. Effective selection and location of sensors in the operating engine environment enables accurate real-time condition monitoring and rapid engine controller response to mitigate critical fault conditions. These capabilities are crucial to ensure crew safety and mission success. Effective sensor selection also facilitates postflight condition assessment, which contributes to efficient engine maintenance and reduced operating costs. Under the Next Generation Launch Technology program, the NASA Glenn Research Center, in partnership with Rocketdyne Propulsion and Power, has developed a model-based procedure for systematically selecting an optimal sensor suite for assessing rocket engine system health. This optimization process is termed the systematic sensor selection strategy. Engine health management (EHM) systems generally employ multiple diagnostic procedures including data validation, anomaly detection, fault-isolation, and information fusion. The effectiveness of each diagnostic component is affected by the quality, availability, and compatibility of sensor data. Therefore systematic sensor selection is an enabling technology for EHM. Information in three categories is required by the systematic sensor selection strategy. The first category consists of targeted engine fault information; including the description and estimated risk-reduction factor for each identified fault. Risk-reduction factors are used to define and rank the potential merit of timely fault diagnoses. The second category is composed of candidate sensor information; including type, location, and estimated variance in normal operation. The final category includes the definition of fault scenarios characteristic of each targeted engine fault. These scenarios are defined in terms of engine model hardware parameters. Values of these parameters define engine simulations that generate

  15. Microporous polyurethane material for size selective heterogeneous catalysis of the Knoevenagel reaction.

    PubMed

    Dey, Sandeep Kumar; de Sousa Amadeu, Nader; Janiak, Christoph

    2016-06-14

    The first polyurethane material which is microporous (BET surface area of 312 m(2) g(-1)) is prepared by solvothermal synthesis and acts as highly efficient and recyclable heterogeneous catalyst in the Knoevenagel condensation showing size selectivity, and in the Henry reaction showing substrate selectivity under mild reaction conditions. PMID:27240738

  16. Multiplexed parallel reaction monitoring targeting histone modifications on the QExactive mass spectrometer.

    PubMed

    Tang, Hui; Fang, Huasheng; Yin, Eric; Brasier, Allan R; Sowers, Lawrence C; Zhang, Kangling

    2014-06-01

    Histone acetylation and methylation play an important role in the regulation of gene expression. Irregular patterns of histone global acetylation and methylation have frequently been seen in various diseases. Quantitative analysis of these patterns is of high value for the evaluation of disease development and of outcomes from therapeutic treatment. Targeting histone acetylation and methylation by selected reaction monitoring (SRM) is one of the current quantitative methods. Here, we reported the use of the multiplexed parallel reaction monitoring (PRM) method on the QExactive mass spectrometer to target previously known lysine acetylation and methylation sites of histone H3 and H4 for the purpose of establishing precursor-product pairs for SRM. 55 modified peptides among which 29 were H3 K27/K36 modified peptides were detected from 24 targeted precursor ions included in the inclusion list. The identification was carried out directly from the trypsin digests of core histones that were separated without derivatization on a homemade capillary column packed with Waters YMC ODS-AQ reversed phase materials. Besides documenting the higher-energy c-trap dissociation (HCD) MS(2) spectra of previously known histone H3/H4 acetylated and methylated tryptic peptides, we identified novel H3 K18 methylation, H3 K27 monomethyl/acetyl duel modifications, H2B K23 acetylation, and H4 K20 acetylation in mammalian histones. The information gained from these experiments sets the foundation for quantification of histone modifications by targeted mass spectrometry methods directly from core histone samples. PMID:24823915

  17. The use of performance parameters in monitoring the safety of dams experiencing alkali-aggregate reaction

    SciTech Connect

    Veesaert, C.J.; LaBoon, J.H.

    1995-12-31

    As the Bureau of Reclamation (Reclamation) moves away from design and construction of new water resource projects toward optimizing the management of existing water resource projects, monitoring the condition of high risk structures such as dams becomes very important. To address this need, Reclamation has developed a logical approach of monitoring the safety of a dam over time. This approach analyzes visual and instrumentation performance parameters unique to each dam, Performance parameters specify the expected performance (behavior) of both embankment and concrete dams, including those concrete dams effected by alkali-aggregate reaction. This paper presents an overview of the concept of performance parameters in monitoring the safety of dams, which have experienced alkali-aggregate reaction. Three case studies are presented to illustrate the use of performance parameters in monitoring a dam`s behavior over time, relative to the effects of alkali-aggregate reaction.

  18. Thermodynamically driven, syn-selective vinylogous aldol reaction of tetronamides.

    PubMed

    Karak, Milandip; Barbosa, Luiz C A; Acosta, Jaime A M; Sarotti, Ariel M; Boukouvalas, John

    2016-06-01

    A stereoselective vinylogous aldol reaction of N-monosubstituted tetronamides with aldehydes is described. The procedure is simple and scalable, works well with both aromatic and aliphatic aldehydes, and affords mainly the corresponding syn-aldol adducts. In many cases, the latter are obtained essentially free of their anti-isomers (dr > 99 : 1) in high yields (70-90%). Experimental and computational studies suggest that the observed diastereoselectivity arises through anti-syn isomer interconversion, enabled by an iterative retro-aldol/aldol reaction. PMID:27163151

  19. Intrinsic selectivity in some prebiotic reactions of urazole with sugars

    NASA Astrophysics Data System (ADS)

    Kolb, Vera M.; Colloton, Patricia A.

    2004-02-01

    Urazole (1,2,4-triazolidine-3,5-dione) (1), 4-methylurazole (12), and its carbon analog, 4,4-dimethylpyrazolidine-3,5-dione (18), react with 2-deoxy-D-ribose (2-deoxy-D-erythro-pentose; 6) in an aqueous solution at room temperature in a regioselective manner (a single substitution on a hydrazidic nitrogen, no reaction on the imide nitrogen) to give a mixture of four nucleosides. These are α and β pyranosides (p) and α and β furanosides (f). The α p forms in a stereoselective manner. A crystalline precipitate is formed in each of the above reactions, which is an exclusive enantiospecific product, 1R, 2R α p. 1 with 2-deoxy-L-ribose (10) gives a precipitate with the exclusive 1S, 2S α p stereochemistry. With 2-deoxy-D-glucose (2-deoxy-D-arabino-hexose; 7) the reaction with 1 is stereospecific, since only one isomer, β p, forms in the solution. Causes of enhanced reactivity of 1 with sugars were also studied. It was found that cyclic hydrazide analogs of 1, such as 12 and 18, are reactive, but open-chain analogs, 1,2,-diacetylhydrazine (21) and 1,2-dicarbethoxyhydrazine (22), are not. Although this reactivity assessment was done qualitatively and under restrictive reaction conditions, it still may be valuable for understanding α -effect of hydrazide nucleophiles. The prebiotic significance of our results is discussed.

  20. Excitation functions for production of 46Sc by deuteron and proton beams in natTi: A basis for additional monitor reactions

    NASA Astrophysics Data System (ADS)

    Hermanne, A.; Tárkányi, F.; Takács, S.; Ditrói, F.; Amjed, N.

    2014-11-01

    An objective of a new Coordinated Research Program launched recently by IAEA is to strengthen and broaden the cross section database for monitoring of charged particle beams given in IAEA-TECDOC-1211. One of the suggestions is to complement the widely used natTi(d,x)48V monitor reaction by the natTi(d,x)46Sc reaction having a maximum in a somewhat higher energy. After compilation of the data sets for this reaction available in literature and unpublished data from our earlier experiments, a selection of 20 sets is proposed for statistical fitting and extraction of recommended values. A similar analysis is presented for the natTi(p,x)46Sc reaction where 16 datasets are finally selected.

  1. Language Control in Bilinguals: Monitoring and Response Selection.

    PubMed

    Branzi, Francesca M; Della Rosa, Pasquale A; Canini, Matteo; Costa, Albert; Abutalebi, Jubin

    2016-06-01

    Language control refers to the cognitive mechanism that allows bilinguals to correctly speak in one language avoiding interference from the nontarget language. Bilinguals achieve this feat by engaging brain areas closely related to cognitive control. However, 2 questions still await resolution: whether this network is differently engaged when controlling nonlinguistic representations, and whether this network is differently engaged when control is exerted upon a restricted set of lexical representations that were previously used (i.e., local control) as opposed to control of the entire language system (i.e., global control). In the present event-related functional magnetic resonance imaging study, we investigated these 2 questions by employing linguistic and nonlinguistic blocked switching tasks in the same bilingual participants. We first report that the left prefrontal cortex is driven similarly for control of linguistic and nonlinguistic representations, suggesting its domain-general role in the implementation of response selection. Second, we propose that language control in bilinguals is hierarchically organized with the dorsal anterior cingulate cortex/presupplementary motor area acting as the supervisory attentional system, recruited for increased monitoring demands such as local control in the second language. On the other hand, prefrontal, inferior parietal areas and the caudate would act as the response selection system, tailored for language selection for both local and global control. PMID:25838037

  2. Polyhedral Interpolation for Optimal Reaction Control System Jet Selection

    NASA Technical Reports Server (NTRS)

    Gefert, Leon P.; Wright, Theodore

    2014-01-01

    An efficient algorithm is described for interpolating optimal values for spacecraft Reaction Control System jet firing duty cycles. The algorithm uses the symmetrical geometry of the optimal solution to reduce the number of calculations and data storage requirements to a level that enables implementation on the small real time flight control systems used in spacecraft. The process minimizes acceleration direction errors, maximizes control authority, and minimizes fuel consumption.

  3. Energy disposal in the vibrational-state- and bond-selected reaction of water with hydrogen atoms

    SciTech Connect

    Hsiao, M.C.; Sinha, A.; Crim, F.F. )

    1991-10-17

    The importance of the reaction of water and hydrogen atoms to atmospheric and combustion processes has motivated both theoretical and experimental studies of its dynamics. The measured OH product state distribution from the reaction of vibrationally excited water with thermal hydrogen atoms supports an intuitive picture of selective disposal in this reaction. Excitation of the third overtone of the O-H stretch (4v{sub OH}) in either water or HOD provides enough energy to initiate the reaction, and laser-induced fluorescence (LIF) monitors the state populations of the reaction product OH or OD. The internal energy of the detected product is small compared to the roughly 9,000 cm{sup {minus}1} of available energy. The average rotational and vibrational energies of OH produced from reaction of H{sub 2}O(4v{sub OH}) are 320 {plus minus} 10 and 100 {plus minus} 30 cm{sup {minus}1}. The reaction of HOD(4v{sub OH}) produces OD with average rotational and vibrational energies of 190 {plus minus} 10 and 440 {plus minus} 90 cm{sup {minus}1}. Analysis of Doppler profiles in the LIF excitation spectra shows that the energy in relative translation of the products is no more than 5,000 cm{sup {minus}1}, leaving the substantial balance of available energy in the H{sub 2} product, most likely as vibrational excitation.

  4. Bond-selected chemistry: Vibrational state control of photodissociation and bimolecular reaction

    SciTech Connect

    Crim, F.F.

    1996-08-01

    Controlling chemical reactions with light rests on the idea of exciting a vibration that becomes the reaction coordinate in subsequent chemistry. Vibrational excitation techniques such as infrared or stimulated Raman excitation of fundamental vibrations or vibrational overtone excitation of higher levels permit the preferential cleavage of a bond in a photodissociation or bimolecular reaction. The key to bond-selected chemistry is the initial preparation of a suitable vibrational state followed, in the case of bond-selected photodissociation, by electronic excitation or, in the case of bond-selected bimolecular reaction, by collision with a reactive atom. Such experiments demonstrate bond-selected chemistry, permit detailed comparison to theory, and reveal general principles of vibrational state control of chemical reactions. 76 refs., 8 figs.

  5. Directing reaction pathways by catalyst active-site selection using self-assembled monolayers.

    PubMed

    Pang, Simon H; Schoenbaum, Carolyn A; Schwartz, Daniel K; Medlin, J Will

    2013-01-01

    One key route for controlling reaction selectivity in heterogeneous catalysis is to prepare catalysts that exhibit only specific types of sites required for desired product formation. Here we show that alkanethiolate self-assembled monolayers with varying surface densities can be used to tune selectivity to desired hydrogenation and hydrodeoxygenation products during the reaction of furfural on supported palladium catalysts. Vibrational spectroscopic studies demonstrate that the selectivity improvement is achieved by controlling the availability of specific sites for the hydrogenation of furfural on supported palladium catalysts through the selection of an appropriate alkanethiolate. Increasing self-assembled monolayer density by controlling the steric bulk of the organic tail ligand restricts adsorption on terrace sites and dramatically increases selectivity to desired products furfuryl alcohol and methylfuran. This technique of active-site selection simultaneously serves both to enhance selectivity and provide insight into the reaction mechanism. PMID:24025780

  6. Real-time reaction monitoring by ultrafast 2D NMR on a benchtop spectrometer.

    PubMed

    Gouilleux, Boris; Charrier, Benoît; Danieli, Ernesto; Dumez, Jean-Nicolas; Akoka, Serge; Felpin, François-Xavier; Rodriguez-Zubiri, Mireia; Giraudeau, Patrick

    2015-12-01

    Reaction monitoring is widely used to follow chemical processes in a broad range of application fields. Recently, the development of robust benchtop NMR spectrometers has brought NMR under the fume hood, making it possible to monitor chemical reactions in a safe and accessible environment. However, these low-field NMR approaches suffer from limited resolution leading to strong peak overlaps, which can limit their application range. Here, we propose an approach capable of recording ultrafast 2D NMR spectra on a compact spectrometer and of following in real time reactions in the synthetic chemistry laboratory. This approach--whose potential is shown here on a Heck-Matsuda reaction--is highly versatile; the duration of the measurement can be optimized to follow reactions whose time scale ranges from between a few tens of seconds to a few hours. It makes it possible to monitor complex reactions in non-deuterated solvents, and to confirm in real time the molecular structure of the compounds involved in the reaction while giving access to relevant kinetic parameters. PMID:26501887

  7. Controlling Catalytic Selectivity via Adsorbate Orientation on the Surface: From Furfural Deoxygenation to Reactions of Epoxides.

    PubMed

    Pang, Simon H; Medlin, J Will

    2015-04-16

    Specificity to desired reaction products is the key challenge in designing solid catalysts for reactions involving addition or removal of oxygen to/from organic reactants. This challenge is especially acute for reactions involving multifunctional compounds such as biomass-derived aromatic molecules (e.g., furfural) and functional epoxides (e.g., 1-epoxy-3-butene). Recent surface-level studies have shown that there is a relationship between adsorbate surface orientation and reaction selectivity in the hydrogenation pathways of aromatic oxygenates and the ring-opening or ring-closing pathways of epoxides. Control of the orientation of reaction intermediates on catalytic surfaces by modifying the surface or near-surface environment has been shown to be a promising method of affecting catalytic selectivity for reactions of multifunctional molecules. In this Perspective, we review recent model studies aimed at understanding the surface chemistry for these reactions and studies that utilize this insight to rationally design supported catalysts. PMID:26263134

  8. Investigating the mechanism of the selective hydrogenation reaction of cinnamaldehyde catalyzed by Ptn clusters.

    PubMed

    Li, Laicai; Wang, Wei; Wang, Xiaolan; Zhang, Lin

    2016-08-01

    Cinnamaldehyde (CAL) belongs to the group of aromatic α,β-unsaturated aldehydes; the selective hydrogenation of CAL plays an important role in the fine chemical and pharmaceutical industries. Using Ptn clusters as catalytic models, we studied the selective hydrogenation reaction mechanism for CAL catalyzed by Ptn (n = 6, 10, 14, 18) clusters by means of B3LYP in density functional theory at the 6-31+ G(d) level (the LanL2DZ extra basis set was used for the Pt atom). The rationality of the transition state was proved by vibration frequency analysis and intrinsic reaction coordinate computation. Moreover, atoms in molecules theory and nature bond orbital theory were applied to discuss the interaction among orbitals and the bonding characteristics. The results indicate that three kinds of products, namely 3-phenylpropyl aldehyde, 3-phenyl allyl alcohol and cinnamyl alcohol, are produced in the selective hydrogenation reaction catalyzed by Ptn clusters; each pathway possesses two reaction channels. Ptn clusters are more likely to catalyze the activation and hydrogenation of the C = O bond in CAL molecules, eventually producing cinnamic alcohol, which proves that Ptn clusters have a strong reaction selectivity to catalyze CAL. The reaction selectivity of the catalyzer cluster is closely related to the size of the Ptn cluster, with Pt14 clusters having the greatest reaction selectivity. Graphical Abstract The reaction mechanism for the selective hydrogenation reaction ofcinnamaldehyde catalyzed by Ptn clusters was studied by densityfunctional theory. The reactionselectivity of cluster catalyzer was concluded to be closely related to the size of Ptn clusters, with Pt14 clusters having the greatest reaction selectivity. PMID:27444877

  9. Monitoring method for surface contamination caused by selected antineoplastic agents.

    PubMed

    Larson, R R; Khazaeli, M B; Dillon, H Kenneth

    2002-02-01

    A method of evaluating surface contamination caused by selected antineoplastic agents was studied. The antineoplastic agents tested were cyclophosphamide, ifosfamide, doxorubicin hydrochloride, fluorouracil, and paclitaxel. Each agent was reconstituted and prepared as a stock solution. A 0.1-mL portion of each solution was spread evenly over a 600-cm2 area of a stainless steel surface, a resin countertop surface, and a vinyl flooring surface. After drying, the surfaces were wiped with each of two types of commercially available wiping materials (What-man no. 42 filters and Kimberly-Clark Kimwipes). A blend of methanol, acetonitrile, and buffered water was used both as the wetting agent for wiping the surfaces and as a desorbing solution. The desorbate was analyzed for drug concentration by reverse-phase high-performance liquid chromatography (HPLC). Mean +/- S.D. percent total recovery ranged from 72.4% +/- 17.6% to 95.3% +/- 2.9% for the vinyl surface wiped with filters, 91.5% +/- 5.4% to 104.7% +/- 0.8% for the resin surface wiped with filters, 73.9% +/- 2.3% to 95.3% +/- 1.7% for the stainless steel surface wiped with filters, and 18.2% +/- 1.4% to 372.8% +/- 8.0% for the stainless steel surface wiped with Kimwipes. Results were best for ifosfamide and cyclophosphamide. Kimwipes were deemed ineffective for this monitoring method because an ingredient interfered with the quantitative analytical tests. A wipe-sampling, desorption, and HPLC method for monitoring surface contamination by selected antineoplastic agents was sufficiently accurate and sensitive to evaluate surfaces typically found in both the pharmacy and drug administration areas of oncology treatment facilities. PMID:11862639

  10. Use of electrophysiological monitoring in selective rhizotomy treating glossopharyngeal neuralgia.

    PubMed

    Zhang, Wenhao; Chen, Minjie; Zhang, Weijie; Chai, Ying

    2014-07-01

    The aim of this study was to evaluate the effects of electrophysiological monitoring on selective rhizotomy of the glossopharyngeal nerve (SRGN) in treatment of glossopharyngeal neuralgia (GPN). From December, 2009 to May, 2012, SRGN was carried out on 8 patients with GPN, through a suboccipital sigmoid sinus posterior approach. The electrodes were placed on the cricothyroid muscle (vagus nerve). Two groups of amplitudes (A1 and A2) were recorded. A1 was recorded when the mixed nerve root was stimulated, and A2 when the part of the vagus nerve was stimulated. The glossopharyngeal nerve was sectioned and the vagus nerve was preserved. If A1/A2 < 50%, the mixed nerve root should be sectioned, otherwise the mixed nerve root should be retained. As the representation of vagus nerve, the averages of A1 and A2 were 22 and 36 μV respectively. The 8 patients were followed up for 9-39 months. Seven patients (87.5%) obtained complete pain relief (excellent) without complications such as hoarseness, dysphagia, and cough. One case (12.5%) obtained moderate relief (good), and was under control with carbamazepine at a dosage of 600 mg/d. Cough was occurred in this patient, but relieved in two months. Electrophysiological monitoring in SRGN can improve the efficiency of pain relief and reduce the incidence of complications. PMID:24095216

  11. The Psychophysiological Reactions of Film Viewers While Viewing Selected Cinemagraphic Elements.

    ERIC Educational Resources Information Center

    Smeltzer, Dennis K.

    This study focused on the psychophysiological reactions of viewers seeing such selected cinemagraphic elements as varying camera distances, tracking shots, panning shots, and zooming shots. Subjects (N=29), randomly selected from introductory speech courses, viewed five films that varied in the presence or absence of the selected filmic elements.…

  12. Analysis of selected allergic reactions among psoriatic patients

    PubMed Central

    Filipowska-Grońska, Agata; Kalemba, Michał; Krajewska, Anna; Grzanka, Alicja; Bożek, Andrzej; Jarząb, Jerzy

    2016-01-01

    Introduction Psoriasis is a chronic and recurrent inflammatory skin disease. The aetiology is still unknown in spite of numerous scientific researches. There is very little evidence which does not provide enough knowledge about allergic reactions in psoriatic patients. Based on the fact that the epidermal barrier damage allows different allergen types to penetrate into deep layers of epidermis and skin, we can assume that it may lead to immunological reactions. Aim To investigate the allergic reaction indicators and hypersensitivity assessment about contact, inhalant and food allergens. The results were analysed with regard to clinical disease indicators and progression stage of dermal lesions. Material and methods Eighty patients with psoriasis were examined. The concentration of total IgE antibodies and allergen specific IgE antibodies (asIgE) were analysed. Standard epidermal tests and atopy patch tests were performed. All the patients were estimated for their dermatological condition based on the PASI scale. The control group consisted of 50 patients without psoriasis and allergic history. Results Significantly higher concentration of total E immunoglobulin has been stated in the patients with psoriasis. Higher concentrations of specific allergic IgE antibodies were more often observed in the examined group but the most frequently observed values were present in 1–3 class. The most common airborne allergens were birch, artemisia, timothy and rye pollens. There have not been any significant statistical differences in the case of positive epidermal test results. Conclusions There is slightly expressed hypersensitivity in psoriatic patients. This hypersensitivity degree correlates with the intensification of symptoms. PMID:26985174

  13. Monitoring biodiesel reactions of soybean oil and sunflower oil using ultrasonic parameters

    NASA Astrophysics Data System (ADS)

    Figueiredo, M. K. K.; Silva, C. E. R.; Alvarenga, A. V.; Costa-Félix, R. P. B.

    2015-01-01

    Biodiesel is an innovation that attempts to substitute diesel oil with biomass. The aim of this paper is to show the development of a real-time method to monitor transesterification reactions by using low-power ultrasound and pulse/echo techniques. The results showed that it is possible to identify different events during the transesterification process by using the proposed parameters, showing that the proposed method is a feasible way to monitor the reactions of biodiesel during its fabrication, in real time, and with relatively low- cost equipment.

  14. Interfacial electronic effects control the reaction selectivity of platinum catalysts.

    PubMed

    Chen, Guangxu; Xu, Chaofa; Huang, Xiaoqing; Ye, Jinyu; Gu, Lin; Li, Gang; Tang, Zichao; Wu, Binghui; Yang, Huayan; Zhao, Zipeng; Zhou, Zhiyou; Fu, Gang; Zheng, Nanfeng

    2016-05-01

    Tuning the electronic structure of heterogeneous metal catalysts has emerged as an effective strategy to optimize their catalytic activities. By preparing ethylenediamine-coated ultrathin platinum nanowires as a model catalyst, here we demonstrate an interfacial electronic effect induced by simple organic modifications to control the selectivity of metal nanocatalysts during catalytic hydrogenation. This we apply to produce thermodynamically unfavourable but industrially important compounds, with ultrathin platinum nanowires exhibiting an unexpectedly high selectivity for the production of N-hydroxylanilines, through the partial hydrogenation of nitroaromatics. Mechanistic studies reveal that the electron donation from ethylenediamine makes the surface of platinum nanowires highly electron rich. During catalysis, such an interfacial electronic effect makes the catalytic surface favour the adsorption of electron-deficient reactants over electron-rich substrates (that is, N-hydroxylanilines), thus preventing full hydrogenation. More importantly, this interfacial electronic effect, achieved through simple organic modifications, may now be used for the optimization of commercial platinum catalysts. PMID:26808458

  15. Interfacial electronic effects control the reaction selectivity of platinum catalysts

    NASA Astrophysics Data System (ADS)

    Chen, Guangxu; Xu, Chaofa; Huang, Xiaoqing; Ye, Jinyu; Gu, Lin; Li, Gang; Tang, Zichao; Wu, Binghui; Yang, Huayan; Zhao, Zipeng; Zhou, Zhiyou; Fu, Gang; Zheng, Nanfeng

    2016-05-01

    Tuning the electronic structure of heterogeneous metal catalysts has emerged as an effective strategy to optimize their catalytic activities. By preparing ethylenediamine-coated ultrathin platinum nanowires as a model catalyst, here we demonstrate an interfacial electronic effect induced by simple organic modifications to control the selectivity of metal nanocatalysts during catalytic hydrogenation. This we apply to produce thermodynamically unfavourable but industrially important compounds, with ultrathin platinum nanowires exhibiting an unexpectedly high selectivity for the production of N-hydroxylanilines, through the partial hydrogenation of nitroaromatics. Mechanistic studies reveal that the electron donation from ethylenediamine makes the surface of platinum nanowires highly electron rich. During catalysis, such an interfacial electronic effect makes the catalytic surface favour the adsorption of electron-deficient reactants over electron-rich substrates (that is, N-hydroxylanilines), thus preventing full hydrogenation. More importantly, this interfacial electronic effect, achieved through simple organic modifications, may now be used for the optimization of commercial platinum catalysts.

  16. Entropic factors provide unusual reactivity and selectivity in epoxide-opening reactions promoted by water

    PubMed Central

    Byers, Jeffery A.; Jamison, Timothy F.

    2013-01-01

    Despite the myriad of selective enzymatic reactions that occur in water, chemists have rarely capitalized on the unique properties of this medium to govern selectivity in reactions. Here we report detailed mechanistic investigations of a water-promoted reaction that displays high selectivity for what is generally a disfavored product. A combination of structural and kinetic data indicates not only that synergy between substrate and water suppresses undesired pathways but also that water promotes the desired pathway by stabilizing charge in the transition state, facilitating proton transfer, doubly activating the substrate for reaction, and perhaps most remarkably, reorganizing the substrate into a reactive conformation that leads to the observed product. This approach serves as an outline for a general strategy of exploiting solvent-solute interactions to achieve unusual reactivity in chemical reactions. These findings may also have implications in the biosynthesis of the ladder polyether natural products, such as the brevetoxins and ciguatoxins. PMID:24046369

  17. Entropic factors provide unusual reactivity and selectivity in epoxide-opening reactions promoted by water.

    PubMed

    Byers, Jeffery A; Jamison, Timothy F

    2013-10-15

    Despite the myriad of selective enzymatic reactions that occur in water, chemists have rarely capitalized on the unique properties of this medium to govern selectivity in reactions. Here we report detailed mechanistic investigations of a water-promoted reaction that displays high selectivity for what is generally a disfavored product. A combination of structural and kinetic data indicates not only that synergy between substrate and water suppresses undesired pathways but also that water promotes the desired pathway by stabilizing charge in the transition state, facilitating proton transfer, doubly activating the substrate for reaction, and perhaps most remarkably, reorganizing the substrate into a reactive conformation that leads to the observed product. This approach serves as an outline for a general strategy of exploiting solvent-solute interactions to achieve unusual reactivity in chemical reactions. These findings may also have implications in the biosynthesis of the ladder polyether natural products, such as the brevetoxins and ciguatoxins. PMID:24046369

  18. Mode specificity in bond selective reactions F + HOD → HF + OD and DF + OH

    SciTech Connect

    Song, Hongwei; Guo, Hua

    2015-05-07

    The influence of vibrational excitations in the partially deuterated water (HOD) reactant on its bond selective reactions with F is investigated using a full-dimensional quantum wave packet method on an accurate global potential energy surface. Despite the decidedly early barrier of the F + H{sub 2}O reaction, reactant vibrational excitation in each local stretching mode of HOD is found to significantly enhance the reaction which breaks the excited bond. In the mean time, excitation of the HOD bending mode also enhances the reaction, but with much lower efficacy and weaker bond selectivity. Except for low collision energies, all vibrational modes are more effective in promoting the bond selective reactions than the translational energy. These results are compared with the predictions of the recently proposed sudden vector projection model.

  19. Chiral polymerization in open systems from chiral-selective reaction rates.

    PubMed

    Gleiser, Marcelo; Nelson, Bradley J; Walker, Sara Imari

    2012-08-01

    We investigate the possibility that prebiotic homochirality can be achieved exclusively through chiral-selective reaction rate parameters without any other explicit mechanism for chiral bias. Specifically, we examine an open network of polymerization reactions, where the reaction rates can have chiral-selective values. The reactions are neither autocatalytic nor do they contain explicit enantiomeric cross-inhibition terms. We are thus investigating how rare a set of chiral-selective reaction rates needs to be in order to generate a reasonable amount of chiral bias. We quantify our results adopting a statistical approach: varying both the mean value and the rms dispersion of the relevant reaction rates, we show that moderate to high levels of chiral excess can be achieved with fairly small chiral bias, below 10%. Considering the various unknowns related to prebiotic chemical networks in early Earth and the dependence of reaction rates to environmental properties such as temperature and pressure variations, we argue that homochirality could have been achieved from moderate amounts of chiral selectivity in the reaction rates. PMID:22610131

  20. Photocycloaddition reaction of atropisomeric maleimides: mechanism and selectivity.

    PubMed

    Chang, Xue-Ping; Zheng, Yiying; Cui, Ganglong; Fang, Wei-Hai; Thiel, Walter

    2016-09-21

    We report a density functional study on the mechanism of the [2+2] photocyclization of atropisomeric maleimides. Experimentally, the reaction is known to proceed through the triplet state. We have located all relevant S0 and T1 minima and transition states, as well as the T1/S0 crossing points, and mapped eight stepwise photocyclization pathways for four different conformers in the T1 state that lead to distinct regioisomers. In the preferred four pathways (one for each conformer) the initially formed C-C bond involves the terminal carbon atom of the alkene moiety. This regioselectivity originates from electrostatic preferences (arising from the charge distribution in the polarized C[double bond, length as m-dash]C double bonds) and from the different thermodynamic stability of the resulting triplet diradical intermediates (caused by electron donation effects that stabilize the radical centers). The formation of the second C-C bond is blocked in the T1 state by prohibitively high barriers and thus occurs after intersystem crossing to the ground state. Furthermore, we rationalize substitution effects on enantioselectivity and diastereoselectivity and identify their origin. PMID:27545206

  1. MRMaid, the web-based tool for designing multiple reaction monitoring (MRM) transitions.

    PubMed

    Mead, Jennifer A; Bianco, Luca; Ottone, Vanessa; Barton, Chris; Kay, Richard G; Lilley, Kathryn S; Bond, Nicholas J; Bessant, Conrad

    2009-04-01

    Multiple reaction monitoring (MRM) of peptides uses tandem mass spectrometry to quantify selected proteins of interest, such as those previously identified in differential studies. Using this technique, the specificity of precursor to product transitions is harnessed for quantitative analysis of multiple proteins in a single sample. The design of transitions is critical for the success of MRM experiments, but predicting signal intensity of peptides and fragmentation patterns ab initio is challenging given existing methods. The tool presented here, MRMaid (pronounced "mermaid") offers a novel alternative for rapid design of MRM transitions for the proteomics researcher. The program uses a combination of knowledge of the properties of optimal MRM transitions taken from expert practitioners and literature with MS/MS evidence derived from interrogation of a database of peptide identifications and their associated mass spectra. The tool also predicts retention time using a published model, allowing ordering of transition candidates. By exploiting available knowledge and resources to generate the most reliable transitions, this approach negates the need for theoretical prediction of fragmentation and the need to undertake prior "discovery" MS studies. MRMaid is a modular tool built around the Genome Annotating Proteomic Pipeline framework, providing a web-based solution with both descriptive and graphical visualizations of transitions. Predicted transition candidates are ranked based on a novel transition scoring system, and users may filter the results by selecting optional stringency criteria, such as omitting frequently modified residues, constraining the length of peptides, or omitting missed cleavages. Comparison with published transitions showed that MRMaid successfully predicted the peptide and product ion pairs in the majority of cases with appropriate retention time estimates. As the data content of the Genome Annotating Proteomic Pipeline repository increases

  2. Deuteration of pentacene in benzoic acid: Monitoring the reaction kinetics via low-temperature optical spectroscopy

    SciTech Connect

    Corval, A.; Casalegno, R.; Astilean, S.; Trommsdorff, H.P.

    1992-06-25

    In the deuteration of pentacene in benzoic acid, this reaction is monitored via low-temperature optical spectroscopy to observe the proton-deuterium rate of exchange between the solvent and solute molecules. Of the 14 pentacene protons, 6 have an exchange rate 2 orders of magnitude greater than the remaining 8. 20 refs., 3 figs.

  3. Employing Magnetic Levitation to Monitor Reaction Kinetics and Measure Activation Energy

    ERIC Educational Resources Information Center

    Benz, Lauren; Cesafsky, Karen E.; Le, Tran; Park, Aileen; Malicky, David

    2012-01-01

    This article describes a simple and inexpensive undergraduate-level kinetics experiment that uses magnetic levitation to monitor the progress and determine the activation energy of a condensation reaction on a polymeric solid support. The method employs a cuvette filled with a paramagnetic solution positioned between two strong magnets. The…

  4. RAPID MONITORING BY QUANTITATIVE POLYMERASE CHAIN REACTION FOR PATHOGENIC ASPERGILLUS DURING CARPET REMOVAL FROM A HOSPITAL

    EPA Science Inventory

    Monitoring for pathogenic Aspergillus species using a rapid, highly sensitive, quantitative polumerase chain reaction technique during carpet removal in a burn unit provided data which allowed the patients to be safely returned to the re-floored area sooner than if only conventio...

  5. Monitoring of water quality of selected wells in Brno district

    NASA Astrophysics Data System (ADS)

    Marková, Jana; Harbuľáková, Vlasta Ondrejka

    2016-06-01

    The article deals with two wells in the country of Brno-district (Brčálka well and Well Olšová). The aim of work was monitoring of elementary parameters of water at regular monthly intervals to measure: water temperature, pH values, solubility oxygen and spring yield. According to the client's requirements (Lesy města Brno) laboratory analyzes of selected parameters were done twice a year and their results were compared with Ministry of Health Decree no. 252/2004 Coll.. These parameters: nitrate, chemical oxygen demand (COD), calcium and magnesium and its values are presented in graphs, for ammonium ions and nitrite in the table. Graphical interpretation of spring yields dependence on the monthly total rainfall and dependence of water temperature on ambient temperature was utilized. The most important features of wells include a water source, a landmark in the landscape, aesthetic element or resting and relaxing place. Maintaining wells is important in terms of future generations.

  6. Weighted next reaction method and parameter selection for efficient simulation of rare events in biochemical reaction systems

    PubMed Central

    2011-01-01

    The weighted stochastic simulation algorithm (wSSA) recently developed by Kuwahara and Mura and the refined wSSA proposed by Gillespie et al. based on the importance sampling technique open the door for efficient estimation of the probability of rare events in biochemical reaction systems. In this paper, we first apply the importance sampling technique to the next reaction method (NRM) of the stochastic simulation algorithm and develop a weighted NRM (wNRM). We then develop a systematic method for selecting the values of importance sampling parameters, which can be applied to both the wSSA and the wNRM. Numerical results demonstrate that our parameter selection method can substantially improve the performance of the wSSA and the wNRM in terms of simulation efficiency and accuracy. PMID:21910924

  7. Quantitative high-resolution on-line NMR spectroscopy in reaction and process monitoring.

    PubMed

    Maiwald, Michael; Fischer, Holger H; Kim, Young-Kyu; Albert, Klaus; Hasse, Hans

    2004-02-01

    On-line nuclear magnetic resonance spectroscopy (on-line NMR) is a powerful technique for reaction and process monitoring. Different set-ups for direct coupling of reaction and separation equipment with on-line NMR spectroscopy are described. NMR spectroscopy can be used to obtain both qualitative and quantitative information from complex reacting multicomponent mixtures for equilibrium or reaction kinetic studies. Commercial NMR probes can be used at pressures up to 35 MPa and temperatures up to 400 K. Applications are presented for studies of equilibria and kinetics of complex formaldehyde-containing mixtures as well as homogeneously and heterogeneously catalyzed esterification kinetics. Direct coupling of a thin-film evaporator is described as an example for the benefits of on-line NMR spectroscopy in process monitoring. PMID:14729025

  8. Real-time monitoring of single-molecule reactions in aqueous solution

    SciTech Connect

    Hong, Xiao; Xu, N.; Yeung, E.S. |

    1997-12-31

    Direct measurement of dynamics of single molecules, e.g., rhodamine 6G (R-6G) and single R-6G tagged with single biological molecules in aqueous solution, was achieved by using thin-layer laser-induced total internal reflection fluorescence microscopy (TLTIRFM). Single-molecule reactions can be directly and simultaneously monitored with spatial resolution down to 0.2 {mu}m and temporal resolution down to 0.2 ms. Dynamics of single-molecule reactions, for example, single dye molecules reacting with a proton and single proteins adsorbing on an active surface, are investigated and evident by monitoring their reaction environment, e.g., temperature and pH. Novel approaches and applications of these studies will be prospected in this presentation.

  9. Catalytic conversion reactions in nanoporous systems with concentration-dependent selectivity: Statistical mechanical modeling

    DOE PAGESBeta

    Garcia, Andres; Wang, Jing; Windus, Theresa L.; Sadow, Aaron D.; Evans, James W.

    2016-05-20

    Statistical mechanical modeling is developed to describe a catalytic conversion reaction A → Bc or Bt with concentration-dependent selectivity of the products, Bc or Bt, where reaction occurs inside catalytic particles traversed by narrow linear nanopores. The associated restricted diffusive transport, which in the extreme case is described by single-file diffusion, naturally induces strong concentration gradients. Hence, by comparing kinetic Monte Carlo simulation results with analytic treatments, selectivity is shown to be impacted by strong spatial correlations induced by restricted diffusivity in the presence of reaction and also by a subtle clustering of reactants, A.

  10. Catalytic conversion reactions in nanoporous systems with concentration-dependent selectivity: Statistical mechanical modeling

    NASA Astrophysics Data System (ADS)

    García, Andrés; Wang, Jing; Windus, Theresa L.; Sadow, Aaron D.; Evans, James W.

    2016-05-01

    Statistical mechanical modeling is developed to describe a catalytic conversion reaction A →Bc or Bt with concentration-dependent selectivity of the products, Bc or Bt, where reaction occurs inside catalytic particles traversed by narrow linear nanopores. The associated restricted diffusive transport, which in the extreme case is described by single-file diffusion, naturally induces strong concentration gradients. Furthermore, by comparing kinetic Monte Carlo simulation results with analytic treatments, selectivity is shown to be impacted by strong spatial correlations induced by restricted diffusivity in the presence of reaction and also by a subtle clustering of reactants, A .

  11. Lewis Acid Catalyzed Selective Reactions of Donor-Acceptor Cyclopropanes with 2-Naphthols.

    PubMed

    Kaicharla, Trinadh; Roy, Tony; Thangaraj, Manikandan; Gonnade, Rajesh G; Biju, Akkattu T

    2016-08-16

    Lewis acid-catalyzed reactions of 2-substituted cyclopropane 1,1-dicarboxylates with 2-naphthols is reported. The reaction exhibits tunable selectivity depending on the nature of Lewis acid employed and proceed as a dearomatization/rearomatization sequence. With Bi(OTf)3 as the Lewis acid, a highly selective dehydrative [3+2] cyclopentannulation takes place leading to the formation of naphthalene-fused cyclopentanes. Interestingly, engaging Sc(OTf)3 as the Lewis acid, a Friedel-Crafts-type addition of 2-naphthols to cyclopropanes takes place, thus affording functionalized 2-naphthols. Both reactions furnished the target products in high regioselectivity and moderate to high yields. PMID:27391792

  12. Monitoring Acidophilic Microbes with Real-Time Polymerase Chain Reaction (PCR) Assays

    SciTech Connect

    Frank F. Roberto

    2008-08-01

    Many techniques that are used to characterize and monitor microbial populations associated with sulfide mineral bioleaching require the cultivation of the organisms on solid or liquid media. Chemolithotrophic species, such as Acidithiobacillus ferrooxidans and Leptospirillum ferrooxidans, or thermophilic chemolithotrophs, such as Acidianus brierleyi and Sulfolobus solfataricus can grow quite slowly, requiring weeks to complete efforts to identify and quantify these microbes associated with bioleach samples. Real-time PCR (polymerase chain reaction) assays in which DNA targets are amplified in the presence of fluorescent oligonucleotide primers, allowing the monitoring and quantification of the amplification reactions as they progress, provide a means of rapidly detecting the presence of microbial species of interest, and their relative abundance in a sample. This presentation will describe the design and use of such assays to monitor acidophilic microbes in the environment and in bioleaching operations. These assays provide results within 2-3 hours, and can detect less than 100 individual microbial cells.

  13. Method and reaction pathway for selectively oxidizing organic compounds

    DOEpatents

    Camaioni, Donald M.; Lilga, Michael A.

    1998-01-01

    A method of selectively oxidizing an organic compound in a single vessel comprises: a) combining an organic compound, an acid solution in which the organic compound is soluble, a compound containing two oxygen atoms bonded to one another, and a metal ion reducing agent capable of reducing one of such oxygen atoms, and thereby forming a mixture; b) reducing the compound containing the two oxygen atoms by reducing one of such oxygen atoms with the metal ion reducing agent to, 1) oxidize the metal ion reducing agent to a higher valence state, and 2) produce an oxygen containing intermediate capable of oxidizing the organic compound; c) reacting the oxygen containing intermediate with the organic compound to oxidize the organic compound into an oxidized organic intermediate, the oxidized organic intermediate having an oxidized carbon atom; d) reacting the oxidized organic intermediate with the acid counter ion and higher valence state metal ion to bond the acid counter ion to the oxidized carbon atom and thereby produce a quantity of an ester incorporating the organic intermediate and acid counter ion; and e) reacting the oxidized organic intermediate with the higher valence state metal ion and water to produce a quantity of alcohol which is less than the quantity of ester, the acid counter ion incorporated in the ester rendering the carbon atom bonded to the counter ion less reactive with the oxygen containing intermediate in the mixture than is the alcohol with the oxygen containing intermediate.

  14. Thermostatted micro-reactor NMR probe head for monitoring fast reactions

    NASA Astrophysics Data System (ADS)

    Brächer, A.; Hoch, S.; Albert, K.; Kost, H. J.; Werner, B.; von Harbou, E.; Hasse, H.

    2014-05-01

    A novel nuclear magnetic resonance (NMR) probe head for monitoring fast chemical reactions is described. It combines micro-reaction technology with capillary flow NMR spectroscopy. Two reactants are fed separately into the probe head where they are effectively mixed in a micro-mixer. The mixed reactants then pass through a capillary NMR flow cell that is equipped with a solenoidal radiofrequency coil where the NMR signal is acquired. The whole flow path of the reactants is thermostatted using the liquid FC-43 (perfluorotributylamine) so that exothermic and endothermic reactions can be studied under almost isothermal conditions. The set-up enables kinetic investigation of reactions with time constants of only a few seconds. Non-reactive mixing experiments carried out with the new probe head demonstrate that it facilitates the acquisition of constant highly resolved NMR signals suitable for quantification of different species in technical mixtures. Reaction kinetic measurements on a test system are presented that prove the applicability of the novel NMR probe head for monitoring fast reactions.

  15. Thermostatted micro-reactor NMR probe head for monitoring fast reactions.

    PubMed

    Brächer, A; Hoch, S; Albert, K; Kost, H J; Werner, B; von Harbou, E; Hasse, H

    2014-05-01

    A novel nuclear magnetic resonance (NMR) probe head for monitoring fast chemical reactions is described. It combines micro-reaction technology with capillary flow NMR spectroscopy. Two reactants are fed separately into the probe head where they are effectively mixed in a micro-mixer. The mixed reactants then pass through a capillary NMR flow cell that is equipped with a solenoidal radiofrequency coil where the NMR signal is acquired. The whole flow path of the reactants is thermostatted using the liquid FC-43 (perfluorotributylamine) so that exothermic and endothermic reactions can be studied under almost isothermal conditions. The set-up enables kinetic investigation of reactions with time constants of only a few seconds. Non-reactive mixing experiments carried out with the new probe head demonstrate that it facilitates the acquisition of constant highly resolved NMR signals suitable for quantification of different species in technical mixtures. Reaction kinetic measurements on a test system are presented that prove the applicability of the novel NMR probe head for monitoring fast reactions. PMID:24650728

  16. Monitors.

    ERIC Educational Resources Information Center

    Powell, David

    1984-01-01

    Provides guidelines for selecting a monitor to suit specific applications, explains the process by which graphics images are produced on a CRT monitor, and describes four types of flat-panel displays being used in the newest lap-sized portable computers. A comparison chart provides prices and specifications for over 80 monitors. (MBR)

  17. Cavitands as Reaction Vessels and Blocking Groups for Selective Reactions in Water.

    PubMed

    Masseroni, Daniele; Mosca, Simone; Mower, Matthew P; Blackmond, Donna G; Rebek, Julius

    2016-07-11

    The majority of reactions currently performed in the chemical industry take place in organic solvents, compounds that are generally derived from petrochemicals. To promote chemical processes in water, we examined the use of synthetic, deep water-soluble cavitands in the Staudinger reduction of long-chain aliphatic diazides (C8 , C10 , and C12 ). The diazide substrates are taken up by the cavitand in D2 O in folded, dynamic conformations. The reduction of one azide group to an amine gives a complex in which the substrate is fixed in an unsymmetrical conformation, with the amine terminal exposed and the azide terminal deep and inaccessible within the cavitand. Accordingly, the reduction of the second azide group is inhibited, even with excess phosphine, and good yields of the monofunctionalized products are obtained. In contrast, the reduction of the free diazides in bulk solution yields diamine products. PMID:27254667

  18. Investigations of natTi(d,x)48V nuclear reactions for beam monitoring purposes

    NASA Astrophysics Data System (ADS)

    Khandaker, Mayeen Uddin; Haba, Hiromitsu; Kanaya, Jumpei; Otuka, Naohiko; Kassim, Hasan Abu; Amin, Yusoff Mohd

    2013-05-01

    We investigated the natTi(d,x)48V reaction cross-sections by using a stacked-foil activation technique in combination with HPGe γ-ray spectrometry at the AVF cyclotron facility of the RIKEN RI Beam Factory, Wako, Japan. An overall good agreement is found between the measured data and the literature ones, whereas partial agreement is obtained with the theoretical data extracted from the TENDL-2011 library provided by the TALYS model calculations. Measured cross-sections of natTi(d,x)48V reactions find significance in monitoring of deuteron beam parameters from threshold to 50 MeV. Furthermore, IAEA recommended cross-sections of natTi(d,x)48V reaction has been verified here, and found a very good agreement. Additionally, measured cross-sections of the natTi(d,x)48V reactions find significance in various practical applications including nuclear medicine.

  19. FutureGen 2.0 Monitoring Program: An Overview of the Monitoring Approach and Technologies Selected for Implementation

    SciTech Connect

    Vermeul, Vince R.; Strickland, Chris E.; Thorne, Paul D.; Bjornstad, Bruce N.; Mackley, Rob D.; Kelly, Mark E.; Sullivan, Charlotte; Williams, Mark D.; Amonette, James E.; Downs, Janelle L.; Fritz, Brad G.; Szecsody, Jim E.; Bonneville, Alain; Gilmore, Tyler J.

    2014-12-31

    The FutureGen 2.0 Project will design and build a first-of-its-kind, near-zero emissions coal-fueled power plant with carbon capture and storage (CCS). To assess storage site performance and meet the regulatory requirements of the Class VI Underground Injection Control (UIC) Program for CO2 Geologic Sequestration, the FutureGen 2.0 project will implement a suite of monitoring technologies designed to 1) evaluate CO2 mass balance and 2) detect any unforeseen loss in CO2 containment. The monitoring program will include direct monitoring of the injection stream and reservoir, and early-leak-detection monitoring directly above the primary confining zone. It will also implement an adaptive monitoring strategy whereby monitoring results are continually evaluated and the monitoring network is modified as required, including the option to drill additional wells in out-years. Wells will be monitored for changes in CO2 concentration and formation pressure, and other geochemical/isotopic signatures that provide indication of CO2 or brine leakage. Indirect geophysical monitoring technologies that were selected for implementation include passive seismic, integrated surface deformation, time-lapse gravity, and pulsed neutron capture logging. Near-surface monitoring approaches that have been initiated include surficial aquifer and surface- water monitoring, soil-gas monitoring, atmospheric monitoring, and hyperspectral data acquisition for assessment of vegetation conditions. Initially, only the collection of baseline data sets is planned; the need for additional near- surface monitoring will be continually evaluated throughout the design and operational phases of the project, and selected approaches may be reinstituted if conditions warrant. Given the current conceptual understanding of the subsurface environment, early and appreciable impacts to near-surface environments are not expected.

  20. Implications of sterically constrained n-butane oxidation reactions on the reaction mechanism and selectivity to 1-butanol

    NASA Astrophysics Data System (ADS)

    Dix, Sean T.; Gómez-Gualdrón, Diego A.; Getman, Rachel B.

    2016-11-01

    Density functional theory (DFT) is used to analyze the reaction network in n-butane oxidation to 1-butanol over a Ag/Pd alloy catalyst under steric constraints, and the implications on the ability to produce 1-butanol selectively using MOF-encapsulated catalysts are discussed. MOFs are porous crystalline solids comprised of metal nodes linked by organic molecules. Recently, they have been successfully grown around metal nanoparticle catalysts. The resulting porous networks have been shown to promote regioselective chemistry, i.e., hydrogenation of trans-1,3-hexadiene to 3-hexene, presumably by forcing the linear alkene to stand "upright" on the catalyst surface and allowing only the terminal C-H bonds to be activated. In this work, we extend this concept to alkane oxidation. Our goal is to determine if a MOF-encapsulated catalyst could be used to selectively produce 1-butanol. Reaction energies and activation barriers are presented for more than 40 reactions in the pathway for n-butane oxidation. We find that C-H bond activation proceeds through an oxygen-assisted pathway and that butanal and 1-butanol are some of the possible products.

  1. Chemical profiling of cerebrospinal fluid by multiple reaction monitoring mass spectrometry.

    PubMed

    Ferreira, Christina R; Yannell, Karen E; Mollenhauer, Brit; Espy, Ryan D; Cordeiro, Fernanda B; Ouyang, Z; Cooks, R G

    2016-09-21

    We report an accelerated biomarker discovery workflow and results of sample screening by mass spectrometry based on multiple reaction monitoring (MRM). This methodology shows promising initial results for the currently unsolved challenge of Parkinson's disease (PD) laboratory diagnosis by biomarker screening. Small molecules present in cerebrospinal fluid (CSF) at low parts per million levels are monitored using specific transitions connecting ion pairs. A set of such transitions constitutes a multidimensional chemical profile used to distinguish and characterize different CSF samples using multivariate statistical methods. PMID:27517482

  2. Pulsed Multiple Reaction Monitoring Approach to Enhancing Sensitivity of a Tandem Quadrupole Mass Spectrometer

    PubMed Central

    Belov, Mikhail E.; Prasad, Satendra; Prior, David C.; Danielson, William F.; Weitz, Karl; Ibrahim, Yehia M.; Smith, Richard D.

    2011-01-01

    Liquid chromatography (LC)–triple quadrupole mass spectrometers operating in a multiple reaction monitoring (MRM) mode are increasingly used for quantitative analysis of low-abundance analytes in highly complex biochemical matrixes. After development and selection of optimum MRM transitions, sensitivity and data quality limitations are largely related to mass spectral peak interferences from sample or matrix constituents and statistical limitations at low number of ions reaching the detector. Herein, we report on a new approach to enhancing MRM sensitivity by converting the continuous stream of ions from the ion source into a pulsed ion beam through the use of an ion funnel trap (IFT). Evaluation of the pulsed MRM approach was performed with a tryptic digest of Shewanella oneidensis strain MR-1 spiked with several model peptides. The sensitivity improvement observed with the IFT coupled in to the triple quadrupole instrument is based on several unique features. First, ion accumulation radio frequency (rf) ion trap facilitates improved droplet desolvation, which is manifested in the reduced background ion noise at the detector. Second, signal amplitude for a given transition is enhanced because of an order-of-magnitude increase in the ion charge density compared to a continuous mode of operation. Third, signal detection at the full duty cycle is obtained, as the trap use eliminates dead times between transitions, which are inevitable with continuous ion streams. In comparison with the conventional approach, the pulsed MRM signals showed 5-fold enhanced peak amplitude and 2–3-fold reduced chemical background, resulting in an improvement in the limit of detection (LOD) by a factor of ~4–8. PMID:21344863

  3. Harnessing the Versatility of Continuous-Flow Processes: Selective and Efficient Reactions.

    PubMed

    Mándity, István M; Ötvös, Sándor B; Szőlősi, György; Fülöp, Ferenc

    2016-06-01

    There is a great need for effective transformations and a broad range of novel chemical entities. Continuous-flow (CF) approaches are of considerable current interest: highly efficient and selective reactions can be performed in CF reactors. The reaction setup of CF reactors offers a wide variety of possible points where versatility can be introduced. This article presents a number of selective and highly efficient gas-liquid-solid and liquid-solid reactions involving a range of reagents and immobilized catalysts. Enantioselective transformations through catalytic hydrogenation and organocatalytic reactions are included, and isotopically labelled compounds and pharmaceutically relevant 1,2,3-triazoles are synthesized in CF reactors. Importantly, the catalyst bed can be changed to a solid-phase peptide synthesis resin, with which peptide synthesis can be performed with the utilization of only 1.5 equivalents of the amino acid. PMID:26997251

  4. FutureGen 2.0 Monitoring Program: An Overview of the Monitoring Approach and Technologies Selected for Implementation

    DOE PAGESBeta

    Vermeul, Vince R.; Strickland, Chris E.; Thorne, Paul D.; Bjornstad, Bruce N.; Mackley, Rob D.; Kelly, Mark E.; Sullivan, Charlotte; Williams, Mark D.; Amonette, James E.; Downs, Janelle L.; et al

    2014-12-31

    The FutureGen 2.0 Project will design and build a first-of-its-kind, near-zero emissions coal-fueled power plant with carbon capture and storage (CCS). To assess storage site performance and meet the regulatory requirements of the Class VI Underground Injection Control (UIC) Program for CO2 Geologic Sequestration, the FutureGen 2.0 project will implement a suite of monitoring technologies designed to 1) evaluate CO2 mass balance and 2) detect any unforeseen loss in CO2 containment. The monitoring program will include direct monitoring of the injection stream and reservoir, and early-leak-detection monitoring directly above the primary confining zone. It will also implement an adaptive monitoringmore » strategy whereby monitoring results are continually evaluated and the monitoring network is modified as required, including the option to drill additional wells in out-years. Wells will be monitored for changes in CO2 concentration and formation pressure, and other geochemical/isotopic signatures that provide indication of CO2 or brine leakage. Indirect geophysical monitoring technologies that were selected for implementation include passive seismic, integrated surface deformation, time-lapse gravity, and pulsed neutron capture logging. Near-surface monitoring approaches that have been initiated include surficial aquifer and surface- water monitoring, soil-gas monitoring, atmospheric monitoring, and hyperspectral data acquisition for assessment of vegetation conditions. Initially, only the collection of baseline data sets is planned; the need for additional near- surface monitoring will be continually evaluated throughout the design and operational phases of the project, and selected approaches may be reinstituted if conditions warrant. Given the current conceptual understanding of the subsurface environment, early and appreciable impacts to near-surface environments are not expected.« less

  5. Metamorphosis of palladium and its relation to selectivity in the Rosenmund reaction

    SciTech Connect

    Maier, W.F.; Chettle, S.J.; Rai, R.S.; Thomas, G.

    1986-05-14

    Drastic changes in morphology and particle sizes of the Pd particles were detected during the classical catalyst pretreatment. These changes are connected to the increase in selectivity as well as to the problems encountered in the Rosenmund reaction. A major action of the poison in Rosenmund reactions was found to be the acceleration of the initial reconstruction of the surface of fresh catalysts to prevent overreduction. The instability of the Pd under reaction conditions appears to be responsible for typical problems encountered with the Rosenmund reaction such as irreproducibility and catalyst deactivation during the reaction. With the use of Pd single crystals stepped and kinked surfaces were found to be active for hydrogenolysis of acid chlorides to aldehydes. Transmission electron microscopy and diffraction have been employed to characterize the change in dispersion and structure of Pd particles on carbon supports after various pretreatments.

  6. Selective and Serial Suzuki-Miyaura Reactions of Polychlorinated Aromatics with Alkyl Pinacol Boronic Esters.

    PubMed

    Laulhé, Sébastien; Blackburn, J Miles; Roizen, Jennifer L

    2016-09-01

    Among cross-coupling reactions, the Suzuki-Miyaura transformation stands out because of its practical advantages, including the commercial availability and low toxicity of the required reagents, mild reaction conditions, and functional group compatibility. Nevertheless, few conditions can be used to cross-couple alkyl boronic acids or esters with aryl halides, especially 2-pyridyl halides. Herein, we describe two novel Suzuki-Miyaura protocols that enable selective conversion of polychlorinated aromatics, with a focus on reactions to convert 2,6-dichloropyridines to 2-chloro-6-alkylpyridines or 2-aryl-6-alkylpyridines. PMID:27537216

  7. Selective Functionalization of Antimycin A Through an N-Transacylation Reaction.

    PubMed

    Chevalier, Arnaud; Zhang, Yanmin; Khdour, Omar M; Hecht, Sidney M

    2016-05-20

    Acylation of 3-(N-formylamino)salicylic acids resulted in transacylation with loss of the formyl moiety. The reaction proceeds through a bis-N-acylated intermediate, which undergoes facile deformylation. This transacylation reaction has been employed for the site-specific functionalization of the mitochondrial poison antimycin A, affording several novel derivatives. The selective cytotoxicity of some of these derivatives toward cultured A549 human lung epithelial adenocarcinoma cells, in comparison with WI-38 normal human lung fibroblasts, illustrates one application of this transacylation reaction. PMID:27168333

  8. Vibrational Control of Bimolecular Reactions with Methane by Mode, Bond, and Stereo Selectivity.

    PubMed

    Liu, Kopin

    2016-05-27

    Vibrational motions of a polyatomic molecule are multifold and can be as simple as stretches or bends or as complex as concerted motions of many atoms. Different modes of excitation often possess different capacities in driving a bimolecular chemical reaction, with distinct dynamic outcomes. Reactions with vibrationally excited methane and its isotopologs serve as a benchmark for advancing our fundamental understanding of polyatomic reaction dynamics. Here, some recent progress in this area is briefly reviewed. Particular emphasis is placed on the key concepts developed from those studies. The interconnections among mode and bond selectivity, Polanyi's rules, and newly introduced vibrational-induced steric phenomena are highlighted. PMID:26980310

  9. Optofluidic UV-Vis spectrophotometer for online monitoring of photocatalytic reactions

    PubMed Central

    Wang, Ning; Tan, Furui; Zhao, Yu; Tsoi, Chi Chung; Fan, Xudong; Yu, Weixing; Zhang, Xuming

    2016-01-01

    On-chip integration of optical detection units into the microfluidic systems for online monitoring is highly desirable for many applications and is also well in line with the spirit of optofluidics technology–fusion of optics and microfluidics for advanced functionalities. This paper reports the construction of a UV-Vis spectrophotometer on a microreactor, and demonstrates the online monitoring of the photocatalytic degradations of methylene blue and methyl orange under different flow rates and different pH values by detecting the intensity change and/or the peak shift. The integrated device consists of a TiO2-coated glass substrate, a PDMS micro-sized reaction chamber and two flow cells. By comparing with the results of commercial equipment, we have found that the measuring range and the sensitivity are acceptable, especially when the transmittance is in the range of 0.01–0.9. This integrated optofluidic device can significantly cut down the test time and the sample volume, and would provide a versatile platform for real-time characterization of photochemical performance. Moreover, its online monitoring capability may enable to access the usually hidden information in biochemical reactions like intermediate products, time-dependent processes and reaction kinetics. PMID:27352840

  10. Immobilized Metal Affinity Chromatography Coupled to Multiple Reaction Monitoring Enables Reproducible Quantification of Phospho-signaling.

    PubMed

    Kennedy, Jacob J; Yan, Ping; Zhao, Lei; Ivey, Richard G; Voytovich, Uliana J; Moore, Heather D; Lin, Chenwei; Pogosova-Agadjanyan, Era L; Stirewalt, Derek L; Reding, Kerryn W; Whiteaker, Jeffrey R; Paulovich, Amanda G

    2016-02-01

    A major goal in cell signaling research is the quantification of phosphorylation pharmacodynamics following perturbations. Traditional methods of studying cellular phospho-signaling measure one analyte at a time with poor standardization, rendering them inadequate for interrogating network biology and contributing to the irreproducibility of preclinical research. In this study, we test the feasibility of circumventing these issues by coupling immobilized metal affinity chromatography (IMAC)-based enrichment of phosphopeptides with targeted, multiple reaction monitoring (MRM) mass spectrometry to achieve precise, specific, standardized, multiplex quantification of phospho-signaling responses. A multiplex immobilized metal affinity chromatography- multiple reaction monitoring assay targeting phospho-analytes responsive to DNA damage was configured, analytically characterized, and deployed to generate phospho-pharmacodynamic curves from primary and immortalized human cells experiencing genotoxic stress. The multiplexed assays demonstrated linear ranges of ≥3 orders of magnitude, median lower limit of quantification of 0.64 fmol on column, median intra-assay variability of 9.3%, median inter-assay variability of 12.7%, and median total CV of 16.0%. The multiplex immobilized metal affinity chromatography- multiple reaction monitoring assay enabled robust quantification of 107 DNA damage-responsive phosphosites from human cells following DNA damage. The assays have been made publicly available as a resource to the community. The approach is generally applicable, enabling wide interrogation of signaling networks. PMID:26621847

  11. Optofluidic UV-Vis spectrophotometer for online monitoring of photocatalytic reactions

    NASA Astrophysics Data System (ADS)

    Wang, Ning; Tan, Furui; Zhao, Yu; Tsoi, Chi Chung; Fan, Xudong; Yu, Weixing; Zhang, Xuming

    2016-06-01

    On-chip integration of optical detection units into the microfluidic systems for online monitoring is highly desirable for many applications and is also well in line with the spirit of optofluidics technology–fusion of optics and microfluidics for advanced functionalities. This paper reports the construction of a UV-Vis spectrophotometer on a microreactor, and demonstrates the online monitoring of the photocatalytic degradations of methylene blue and methyl orange under different flow rates and different pH values by detecting the intensity change and/or the peak shift. The integrated device consists of a TiO2-coated glass substrate, a PDMS micro-sized reaction chamber and two flow cells. By comparing with the results of commercial equipment, we have found that the measuring range and the sensitivity are acceptable, especially when the transmittance is in the range of 0.01–0.9. This integrated optofluidic device can significantly cut down the test time and the sample volume, and would provide a versatile platform for real-time characterization of photochemical performance. Moreover, its online monitoring capability may enable to access the usually hidden information in biochemical reactions like intermediate products, time-dependent processes and reaction kinetics.

  12. Optofluidic UV-Vis spectrophotometer for online monitoring of photocatalytic reactions.

    PubMed

    Wang, Ning; Tan, Furui; Zhao, Yu; Tsoi, Chi Chung; Fan, Xudong; Yu, Weixing; Zhang, Xuming

    2016-01-01

    On-chip integration of optical detection units into the microfluidic systems for online monitoring is highly desirable for many applications and is also well in line with the spirit of optofluidics technology-fusion of optics and microfluidics for advanced functionalities. This paper reports the construction of a UV-Vis spectrophotometer on a microreactor, and demonstrates the online monitoring of the photocatalytic degradations of methylene blue and methyl orange under different flow rates and different pH values by detecting the intensity change and/or the peak shift. The integrated device consists of a TiO2-coated glass substrate, a PDMS micro-sized reaction chamber and two flow cells. By comparing with the results of commercial equipment, we have found that the measuring range and the sensitivity are acceptable, especially when the transmittance is in the range of 0.01-0.9. This integrated optofluidic device can significantly cut down the test time and the sample volume, and would provide a versatile platform for real-time characterization of photochemical performance. Moreover, its online monitoring capability may enable to access the usually hidden information in biochemical reactions like intermediate products, time-dependent processes and reaction kinetics. PMID:27352840

  13. The selection reaction of homogeneous catalyst in soy-epoxide hydroxylation

    NASA Astrophysics Data System (ADS)

    Elvistia Firdaus, Flora

    2014-04-01

    Hydroxylation reaction of soy-epoxide has resulted soy-polyol; a prepolymeric material for polyurethane. The conversion and selectivity of soy-epoxide butanol based to hydroxylation was found higher than soy-ethylene glycol (EG) based. These reactions were performed by sulfur acid which commonly known as homogeneous catalyst. Conversion and selectivity of homogeneous catalyst compared to bentonite; a heteregeneous catalyst was lower as in fact the mixtures were more viscous. The catalysis were significantly effected to cell morphology. Foams were conducted by heterogeneous catalyst resulted an irregular form of windows while homogeneous catalyst are more ordered.

  14. Branched Arylalkenes from Cinnamates: Selectivity Inversion in Heck Reactions by Carboxylates as Deciduous Directing Groups.

    PubMed

    Tang, Jie; Hackenberger, Dagmar; Goossen, Lukas J

    2016-09-01

    A decarboxylative Mizoroki-Heck coupling of aryl halides with cinnamic acids has been developed in which the carboxylate group directs the arylation into its β-position before being tracelessly removed through protodecarboxylation. In the presence of a copper/palladium catalyst, both electron-rich and electron-deficient aryl bromides and chlorides bearing numerous functionalities were successfully coupled with broadly available cinnamates, with selective formation of 1,1-disubstituted alkenes. This reaction concept, in which the carboxylate acts as a deciduous directing group, ideally complements traditional 1,2-selective Heck reactions of styrenes. PMID:27485163

  15. To Track or Not to Track: User Reactions to Concepts in Longitudinal Health Monitoring

    PubMed Central

    Intille, Stephen S; Morris, Margaret E

    2006-01-01

    Background Advances in ubiquitous computing, smart homes, and sensor technologies enable novel, longitudinal health monitoring applications in the home. Many home monitoring technologies have been proposed to detect health crises, support aging-in-place, and improve medical care. Health professionals and potential end users in the lay public, however, sometimes question whether home health monitoring is justified given the cost and potential invasion of privacy. Objective The aim of the study was to elicit specific feedback from health professionals and laypeople about how they might use longitudinal health monitoring data for proactive health and well-being. Methods Interviews were conducted with 8 health professionals and 26 laypeople. Participants were asked to evaluate mock data visualization displays that could be generated by novel home monitoring systems. The mock displays were used to elicit reactions to longitudinal monitoring in the home setting as well as what behaviors, events, and physiological indicators people were interested in tracking. Results Based on the qualitative data provided by the interviews, lists of benefits of and concerns about health tracking from the perspectives of the practitioners and laypeople were compiled. Variables of particular interest to the interviewees, as well as their specific ideas for applications of collected data, were documented. Conclusions Based upon these interviews, we recommend that ubiquitous “monitoring” systems may be more readily adopted if they are developed as tools for personalized, longitudinal self-investigation that help end users learn about the conditions and variables that impact their social, cognitive, and physical health. PMID:17236264

  16. [Methods Used for Monitoring Cure Reactions in Real-time in an Autoclave

    NASA Technical Reports Server (NTRS)

    Cooper, John B.; Wise, Kent L.; Jensen, Brian J. (Technical Monitor)

    2000-01-01

    The goal of the research was to investigate methods for monitoring cure reactions in real-time in an autoclave. This is of particular importance to NASA Langley Research Center because polyimides were proposed for use in the High Speed Civil Transport (HSCT) program. Understanding the cure chemistry behind the polyimides would allow for intelligent processing of the composites made from their use. This work has led to two publications in peer-reviewed journals and a patent. The journal articles are listed as Appendix A which is on the instrument design of the research and Appendix B which is on the cure chemistry. Also, a patent has been awarded for the instrumental design developed under this grant which is given as Appendix C. There has been a significant amount of research directed at developing methods for monitoring cure reactions in real-time within the autoclave. The various research efforts can be categorized as methods providing either direct chemical bonding information or methods that provide indirect chemical bonding information. Methods falling into the latter category are fluorescence, dielectric loss, ultrasonic and similar type methods. Correlation of such measurements with the underlying chemistry is often quite difficult since these techniques do not allow monitoring of the curing chemistry which is ultimately responsible for material properties. Direct methods such as vibrational spectroscopy, however, can often be easily correlated with the underlying chemistry of a reaction. Such methods include Raman spectroscopy, mid-IR absorbance, and near-IR absorbance. With the recent advances in fiber-optics, these spectroscopic techniques can be applied to remote on-line monitoring.

  17. Site selection criteria for the optical atmospheric visibility monitoring telescopes

    NASA Technical Reports Server (NTRS)

    Cowles, K.

    1989-01-01

    A description of each of the criteria used to decide where to locate the Atmospheric Visibility Monitoring (AVM) telescope systems is given, along with a weighting factor for each of them. These criteria include low probability of clouds, fog, smog, haze, low scattering, low turbulence, availability of security and maintenance, and suitability of a site for a potential optical reception station. They will be used to determine which three of several sites under consideration will be used for monitoring visibility through the atmosphere as it applies to an optical ground-based receiving network as may be used in NASA space missions in decades to come.

  18. Process for chemical reaction of amino acids and amides yielding selective conversion products

    DOEpatents

    Holladay, Jonathan E.

    2006-05-23

    The invention relates to processes for converting amino acids and amides to desirable conversion products including pyrrolidines, pyrrolidinones, and other N-substituted products. L-glutamic acid and L-pyroglutamic acid provide general reaction pathways to numerous and valuable selective conversion products with varied potential industrial uses.

  19. Powerful fluoroalkoxy molybdenum(V) reagent for selective oxidative arene coupling reaction.

    PubMed

    Schubert, Moritz; Leppin, Jana; Wehming, Kathrin; Schollmeyer, Dieter; Heinze, Katja; Waldvogel, Siegfried R

    2014-02-24

    We introduce the novel fluoroalkoxy molybdenum(V) reagent 1 which has superior reactivity and selectivity in comparison to MoCl5 or the MoCl5 /TiCl4 reagent mixture in the oxidative coupling reactions of aryls. Common side reactions, such as chlorination and/or oligomer formation, are drastically diminished creating a powerful and useful reagent for oxidative coupling. Theoretical treatment of the reagent interaction with 1,2-dimethoxybenzene-type substrates indicates an inner-sphere electron transfer followed by a radical cationic reaction pathway for the oxidative-coupling process. EPR spectroscopic and electrochemical studies, X-ray analyses, computational investigations, and the experimental scope provide a highly consistent picture. The substitution of chlorido ligands by hexafluoroisopropoxido moieties seems to boost both the reactivity and selectivity of the metal center which might be applied to other reagents as well. PMID:24478061

  20. Multi-site assessment of the precision and reproducibility of multiple reaction monitoring-based measurements of proteins in plasma.

    PubMed

    Addona, Terri A; Abbatiello, Susan E; Schilling, Birgit; Skates, Steven J; Mani, D R; Bunk, David M; Spiegelman, Clifford H; Zimmerman, Lisa J; Ham, Amy-Joan L; Keshishian, Hasmik; Hall, Steven C; Allen, Simon; Blackman, Ronald K; Borchers, Christoph H; Buck, Charles; Cardasis, Helene L; Cusack, Michael P; Dodder, Nathan G; Gibson, Bradford W; Held, Jason M; Hiltke, Tara; Jackson, Angela; Johansen, Eric B; Kinsinger, Christopher R; Li, Jing; Mesri, Mehdi; Neubert, Thomas A; Niles, Richard K; Pulsipher, Trenton C; Ransohoff, David; Rodriguez, Henry; Rudnick, Paul A; Smith, Derek; Tabb, David L; Tegeler, Tony J; Variyath, Asokan M; Vega-Montoto, Lorenzo J; Wahlander, Asa; Waldemarson, Sofia; Wang, Mu; Whiteaker, Jeffrey R; Zhao, Lei; Anderson, N Leigh; Fisher, Susan J; Liebler, Daniel C; Paulovich, Amanda G; Regnier, Fred E; Tempst, Paul; Carr, Steven A

    2009-07-01

    Verification of candidate biomarkers relies upon specific, quantitative assays optimized for selective detection of target proteins, and is increasingly viewed as a critical step in the discovery pipeline that bridges unbiased biomarker discovery to preclinical validation. Although individual laboratories have demonstrated that multiple reaction monitoring (MRM) coupled with isotope dilution mass spectrometry can quantify candidate protein biomarkers in plasma, reproducibility and transferability of these assays between laboratories have not been demonstrated. We describe a multilaboratory study to assess reproducibility, recovery, linear dynamic range and limits of detection and quantification of multiplexed, MRM-based assays, conducted by NCI-CPTAC. Using common materials and standardized protocols, we demonstrate that these assays can be highly reproducible within and across laboratories and instrument platforms, and are sensitive to low mug/ml protein concentrations in unfractionated plasma. We provide data and benchmarks against which individual laboratories can compare their performance and evaluate new technologies for biomarker verification in plasma. PMID:19561596

  1. Morphological impact on the reaction kinetics of size-selected cobalt oxide nanoparticles

    SciTech Connect

    Bartling, Stephan Meiwes-Broer, Karl-Heinz; Barke, Ingo; Pohl, Marga-Martina

    2015-09-21

    Apart from large surface areas, low activation energies are essential for efficient reactions, particularly in heterogeneous catalysis. Here, we show that not only the size of nanoparticles but also their detailed morphology can crucially affect reaction kinetics, as demonstrated for mass-selected, soft-landed, and oxidized cobalt clusters in a 6 nm to 18 nm size range. The method of reflection high-energy electron diffraction is extended to the quantitative determination of particle activation energies which is applied for repeated oxidation and reduction cycles at the same particles. We find unexpectedly small activation barriers for the reduction reaction of the largest particles studied, despite generally increasing barriers for growing sizes. We attribute these observations to the interplay of reaction-specific material transport with a size-dependent inner particle morphology.

  2. Monitoring Enzymatic Reactions in Real Time Using Venturi Easy Ambient Sonic-Spray Ionization Mass Spectrometry

    PubMed Central

    2016-01-01

    We developed a technique to monitor spatially confined surface reactions with mass spectrometry under ambient conditions, without the need for voltage or organic solvents. Fused-silica capillaries immersed in an aqueous solution, positioned in close proximity to each other and the functionalized surface, created a laminar flow junction with a resulting reaction volume of ∼5 pL. The setup was operated with a syringe pump, delivering reagents to the surface through a fused-silica capillary. The other fused-silica capillary was connected to a Venturi easy ambient sonic-spray ionization source, sampling the resulting analytes at a slightly higher flow rate compared to the feeding capillary. The combined effects of the inflow and outflow maintains a chemical microenvironment, where the rate of advective transport overcomes diffusion. We show proof-of-concept where acetylcholinesterase was immobilized on an organosiloxane polymer through electrostatic interactions. The hydrolysis of acetylcholine by acetylcholinesterase into choline was monitored in real-time for a range of acetylcholine concentrations, fused-silica capillary geometries, and operating flow rates. Higher reaction rates and conversion yields were observed with increasing acetylcholine concentrations, as would be expected. PMID:27249533

  3. Monitoring Enzymatic Reactions in Real Time Using Venturi Easy Ambient Sonic-Spray Ionization Mass Spectrometry.

    PubMed

    Jansson, Erik T; Dulay, Maria T; Zare, Richard N

    2016-06-21

    We developed a technique to monitor spatially confined surface reactions with mass spectrometry under ambient conditions, without the need for voltage or organic solvents. Fused-silica capillaries immersed in an aqueous solution, positioned in close proximity to each other and the functionalized surface, created a laminar flow junction with a resulting reaction volume of ∼5 pL. The setup was operated with a syringe pump, delivering reagents to the surface through a fused-silica capillary. The other fused-silica capillary was connected to a Venturi easy ambient sonic-spray ionization source, sampling the resulting analytes at a slightly higher flow rate compared to the feeding capillary. The combined effects of the inflow and outflow maintains a chemical microenvironment, where the rate of advective transport overcomes diffusion. We show proof-of-concept where acetylcholinesterase was immobilized on an organosiloxane polymer through electrostatic interactions. The hydrolysis of acetylcholine by acetylcholinesterase into choline was monitored in real-time for a range of acetylcholine concentrations, fused-silica capillary geometries, and operating flow rates. Higher reaction rates and conversion yields were observed with increasing acetylcholine concentrations, as would be expected. PMID:27249533

  4. Analysis of the reactivity and selectivity of fullerene dimerization reactions at the atomic level

    NASA Astrophysics Data System (ADS)

    Koshino, Masanori; Niimi, Yoshiko; Nakamura, Eiichi; Kataura, Hiromichi; Okazaki, Toshiya; Suenaga, Kazutomo; Iijima, Sumio

    2010-02-01

    High-resolution transmission electron microscopy has proved useful for its ability to provide time-resolved images of small molecules and their movements. One of the next challenges in this area is to visualize chemical reactions by monitoring time-dependent changes in the atomic positions of reacting molecules. Such images may provide information that is not available with other experimental methods. Here we report a study on bimolecular reactions of fullerene and metallofullerene molecules inside carbon nanotubes as a function of electron dose. Images of how the fullerenes move during the dimerization process reveal the specific orientations in which two molecules interact, as well as how bond reorganization occurs after their initial contact. Studies on the concentration, specimen temperature, effect of catalyst and accelerating voltage indicate that the reactions can be imaged under a variety of conditions.

  5. Reactions of Propylene Oxide on Supported Silver Catalysts: Insights into Pathways Limiting Epoxidation Selectivity

    SciTech Connect

    Kulkarni, Apoorva; Bedolla-Pantoja, Marco; Singh, Suyash; Lobo, Raul F.; Mavrikakis, Manos; Barteau, Mark A.

    2012-02-04

    The reactions of propylene oxide (PO) on silver catalysts were studied to understand the network of parallel and sequential reactions that may limit the selectivity of propylene epoxidation by these catalysts. The products of the anaerobic reaction of PO on Ag/a-Al2O3 were propanal, acetone and allyl alcohol for PO conversions below 2–3%. As the conversion of PO was increased either by increasing the temperature or the contact time, acrolein was formed at the expense of propanal, indicating that acrolein is a secondary reaction product in PO decomposition. With addition of oxygen to the feedstream the conversion of PO increased moderately. In contrast to the experiments in absence of oxygen, CO2 was a significant product while the selectivity to propanal decreased as soon as oxygen was introduced in the system. Allyl alcohol disappeared completely from the product stream in the presence of oxygen, reacting to form acrolein and CO2. The product distribution may be explained by a network of reactions involving two types of oxametallacycles formed by ring opening of PO: one with the oxygen bonded to C1 (OMC1, linear) and the other with oxygen bonded to C2 (OMC2, branched). OMC1 reacts to form PO, propanal, and allyl alcohol.

  6. [Enlightenment of adverse reaction monitoring on safety evaluation of traditional Chinese medicines].

    PubMed

    Song, Hai-bo; Du, Xiao-xi; Ren, Jing-tian; Yang, Le; Guo, Xiao-xin; Pang, Yu

    2015-04-01

    The adverse reaction monitoring is important in warning the risks of traditional Chinese medicines at an early stage, finding potential quality problems and ensuring the safe clinical medication. In the study, efforts were made to investigate the risk signal mining techniques in line with the characteristics of traditional Chinese medicines, particularly the complexity in component, processing, compatibility, preparation and clinical medication, find early risk signals of traditional Chinese medicines and establish a traditional Chinese medicine safety evaluation system based on adverse reaction risk signals, in order to improve the target studies on traditional Chinese medicine safety, effective and timely control risks and solve the existing frequent safety issue in traditional Chinese medicines. PMID:26281610

  7. Model-based sensor location selection for helicopter gearbox monitoring

    NASA Technical Reports Server (NTRS)

    Jammu, Vinay B.; Wang, Keming; Danai, Kourosh; Lewicki, David G.

    1996-01-01

    A new methodology is introduced to quantify the significance of accelerometer locations for fault diagnosis of helicopter gearboxes. The basis for this methodology is an influence model which represents the effect of various component faults on accelerometer readings. Based on this model, a set of selection indices are defined to characterize the diagnosability of each component, the coverage of each accelerometer, and the relative redundancy between the accelerometers. The effectiveness of these indices is evaluated experimentally by measurement-fault data obtained from an OH-58A main rotor gearbox. These data are used to obtain a ranking of individual accelerometers according to their significance in diagnosis. Comparison between the experimentally obtained rankings and those obtained from the selection indices indicates that the proposed methodology offers a systematic means for accelerometer location selection.

  8. Issues in the Optimal Selection of a Cranial Nerve Monitoring System

    PubMed Central

    Selesnick, Samuel H.; Goldsmith, Daniel F.

    1993-01-01

    Intraoperative nerve monitoring (IONM) is a safe technique that is of clear clinical value in the preservation of cranial nerves in skull base surgery and is rapidly becoming the standard of care. Available nerve monitoring systems vary widely in capabilities and costs. A well-informed surgeon may best decide on monitoring needs based on surgical case selection, experience, operating room space, availability of monitoring personnel, and cost. Key system characteristics that should be reviewed in the decision-making process include the monitoring technique (electromyography, pressure transducer, direct nerve monitoring, brainstem auditory evoked potential) and the stimulus technique (stimulating parameters, probe selection). In the past, IONM has been primarily employed in posterior fossa and temporal bone surgery, but the value of IONM is being recognized in more skull base and head and neck surgeries. Suggested IONM strategies for specific surgeries are presented. PMID:17170916

  9. Simultaneous (19)F-(1)H medium resolution NMR spectroscopy for online reaction monitoring.

    PubMed

    Zientek, Nicolai; Laurain, Clément; Meyer, Klas; Kraume, Matthias; Guthausen, Gisela; Maiwald, Michael

    2014-10-18

    Medium resolution nuclear magnetic resonance (MR-NMR) spectroscopy is currently a fast developing field, which has an enormous potential to become an important analytical tool for reaction monitoring, in hyphenated techniques, and for systematic investigations of complex mixtures. The recent developments of innovative MR-NMR spectrometers are therefore remarkable due to their possible applications in quality control, education, and process monitoring. MR-NMR spectroscopy can beneficially be applied for fast, non-invasive, and volume integrating analyses under rough environmental conditions. Within this study, a simple 1/16″ fluorinated ethylene propylene (FEP) tube with an ID of 0.04″ (1.02mm) was used as a flow cell in combination with a 5mm glass Dewar tube inserted into a benchtop MR-NMR spectrometer with a (1)H Larmor frequency of 43.32MHz and 40.68MHz for (19)F. For the first time, quasi-simultaneous proton and fluorine NMR spectra were recorded with a series of alternating (19)F and (1)H single scan spectra along the reaction time coordinate of a homogeneously catalysed esterification model reaction containing fluorinated compounds. The results were compared to quantitative NMR spectra from a hyphenated 500MHz online NMR instrument for validation. Automation of handling, pre-processing, and analysis of NMR data becomes increasingly important for process monitoring applications of online NMR spectroscopy and for its technical and practical acceptance. Thus, NMR spectra were automatically baseline corrected and phased using the minimum entropy method. Data analysis schemes were designed such that they are based on simple direct integration or first principle line fitting, with the aim that the analysis directly revealed molar concentrations from the spectra. Finally, the performance of 1/16″ FEP tube set-up with an ID of 1.02mm was characterised regarding the limit of detection (LOQ ((1)H)=0.335molL(-1) and LOQ ((19)F)=0.130molL(-1) for trifluoroethanol

  10. Simultaneous 19F-1H medium resolution NMR spectroscopy for online reaction monitoring

    NASA Astrophysics Data System (ADS)

    Zientek, Nicolai; Laurain, Clément; Meyer, Klas; Kraume, Matthias; Guthausen, Gisela; Maiwald, Michael

    2014-12-01

    Medium resolution nuclear magnetic resonance (MR-NMR) spectroscopy is currently a fast developing field, which has an enormous potential to become an important analytical tool for reaction monitoring, in hyphenated techniques, and for systematic investigations of complex mixtures. The recent developments of innovative MR-NMR spectrometers are therefore remarkable due to their possible applications in quality control, education, and process monitoring. MR-NMR spectroscopy can beneficially be applied for fast, non-invasive, and volume integrating analyses under rough environmental conditions. Within this study, a simple 1/16″ fluorinated ethylene propylene (FEP) tube with an ID of 0.04″ (1.02 mm) was used as a flow cell in combination with a 5 mm glass Dewar tube inserted into a benchtop MR-NMR spectrometer with a 1H Larmor frequency of 43.32 MHz and 40.68 MHz for 19F. For the first time, quasi-simultaneous proton and fluorine NMR spectra were recorded with a series of alternating 19F and 1H single scan spectra along the reaction time coordinate of a homogeneously catalysed esterification model reaction containing fluorinated compounds. The results were compared to quantitative NMR spectra from a hyphenated 500 MHz online NMR instrument for validation. Automation of handling, pre-processing, and analysis of NMR data becomes increasingly important for process monitoring applications of online NMR spectroscopy and for its technical and practical acceptance. Thus, NMR spectra were automatically baseline corrected and phased using the minimum entropy method. Data analysis schemes were designed such that they are based on simple direct integration or first principle line fitting, with the aim that the analysis directly revealed molar concentrations from the spectra. Finally, the performance of 1/16″ FEP tube set-up with an ID of 1.02 mm was characterised regarding the limit of detection (LOQ (1H) = 0.335 mol L-1 and LOQ (19F) = 0.130 mol L-1 for trifluoroethanol in

  11. Determination of busulfan in plasma by GC-MS with selected-ion monitoring.

    PubMed

    Ehrsson, H; Hassan, M

    1983-10-01

    A GC-MS technique with selected-ion monitoring is described for the determination of busulfan in plasma. Busulfan is extracted from plasma with methylene chloride and converted to 1,4-diiodobutane. Analysis by GC-MS with selected-ion monitoring (m/z 183) gave a relative standard deviation of +/- 4.3% (n = 5) at the 10-ng/ml level. PMID:6644573

  12. PROCESS OF SELECTING INDICATORS FOR MONITORING CONDITIONS OF RANGELAND HEALTH

    EPA Science Inventory

    This paper reports on a process for selecting a suite of indicators that, in combination, can be useful in assessing the ecological conditions of rangelands. onceptual models that depict the structural and functional properties of ecological processes were used to show the linkag...

  13. Blood-component therapy: selection, administration and monitoring.

    PubMed

    Chiaramonte, Deirdre

    2004-05-01

    Transfusion of blood products is a frequent necessity in small animal practice. Transfusion medicine has become more sophisticated with increased access to blood components, knowledge of blood types, and cross-matching requirements. Although potentially life saving, this procedure does carry some risk. In addition to selecting the appropriate blood product, several steps need to be completed to prepare the product for administration and the patient for receiving a transfusion. PMID:15179925

  14. SiC-BASED HYDROGEN SELECTIVE MEMBRANES FOR WATER-GAS-SHIFT REACTION

    SciTech Connect

    Unknown

    2000-12-01

    A hydrogen selective membrane as a membrane reactor (MR) can significantly improve the power generation efficiency with a reduced capital and operating cost for the waster-gas-shift reaction. Existing hydrogen selective ceramic membranes are not suitable for the proposed MR due to their poor hydrothermal stability. In this project we have focused on the development of innovative silicon carbide (SiC) based hydrogen selective membranes, which can potentially overcome this technical barrier. During Year I, we have successfully fabricated SiC macro porous membranes via extrusion of commercially available SiC powder, which were then deposited with thin, micro-porous (6 to 40{angstrom} in pore size) films via sol-gel technique as intermediate layers. Finally, an SiC hydrogen selective thin film was deposited on this substrate via our CVD/I technique. The composite membrane thus prepared demonstrated excellent hydrogen selectivity at high temperature ({approx}600 C). More importantly, this membrane also exhibited a much improved hydrothermal stability at 600 C with 50% steam (atmospheric pressure) for nearly 100 hours. In parallel, we have explored an alternative approach to develop a H{sub 2} selective SiC membrane via pyrolysis of selected pre-ceramic polymers. Building upon the positive progress made in the Year I preliminary study, we will conduct an optimization study in Year II to develop an optimized H{sub 2} selective SiC membrane with sufficient hydrothermal stability suitable for the WGS environment.

  15. Use of Nanostructure-Initiator Mass Spectrometry to Deduce Selectivity of Reaction in Glycoside Hydrolases.

    PubMed

    Deng, Kai; Takasuka, Taichi E; Bianchetti, Christopher M; Bergeman, Lai F; Adams, Paul D; Northen, Trent R; Fox, Brian G

    2015-01-01

    Chemically synthesized nanostructure-initiator mass spectrometry (NIMS) probes derivatized with tetrasaccharides were used to study the reactivity of representative Clostridium thermocellum β-glucosidase, endoglucanases, and cellobiohydrolase. Diagnostic patterns for reactions of these different classes of enzymes were observed. Results show sequential removal of glucose by the β-glucosidase and a progressive increase in specificity of reaction from endoglucanases to cellobiohydrolase. Time-dependent reactions of these polysaccharide-selective enzymes were modeled by numerical integration, which provides a quantitative basis to make functional distinctions among a continuum of naturally evolved catalytic properties. Consequently, our method, which combines automated protein translation with high-sensitivity and time-dependent detection of multiple products, provides a new approach to annotate glycoside hydrolase phylogenetic trees with functional measurements. PMID:26579511

  16. Selective Heterogeneous C-H Activation/Halogenation Reactions Catalyzed by Pd@MOF Nanocomposites.

    PubMed

    Pascanu, Vlad; Carson, Fabian; Solano, Marta Vico; Su, Jie; Zou, Xiaodong; Johansson, Magnus J; Martín-Matute, Belén

    2016-03-01

    A directed heterogeneous C-H activation/halogenation reaction catalyzed by readily synthesized Pd@MOF nanocatalysts was developed. The heterogeneous Pd catalysts used were a novel and environmentally benign Fe-based metal-organic framework (MOF) (Pd@MIL-88B-NH2 (Fe)) and the previously developed Pd@MIL-101-NH2 (Cr). Very high conversions and selectivities were achieved under very mild reaction conditions and in short reaction times. A wide variety of directing groups, halogen sources, and substitution patterns were well tolerated, and valuable polyhalogenated compounds were synthesized in a controlled manner. The synthesis of the Pd-functionalized Fe-based MOF and the recyclability of the two catalysts are also presented. PMID:26481867

  17. Use of Nanostructure-Initiator Mass Spectrometry to Deduce Selectivity of Reaction in Glycoside Hydrolases

    PubMed Central

    Deng, Kai; Takasuka, Taichi E.; Bianchetti, Christopher M.; Bergeman, Lai F.; Adams, Paul D.; Northen, Trent R.; Fox, Brian G.

    2015-01-01

    Chemically synthesized nanostructure-initiator mass spectrometry (NIMS) probes derivatized with tetrasaccharides were used to study the reactivity of representative Clostridium thermocellum β-glucosidase, endoglucanases, and cellobiohydrolase. Diagnostic patterns for reactions of these different classes of enzymes were observed. Results show sequential removal of glucose by the β-glucosidase and a progressive increase in specificity of reaction from endoglucanases to cellobiohydrolase. Time-dependent reactions of these polysaccharide-selective enzymes were modeled by numerical integration, which provides a quantitative basis to make functional distinctions among a continuum of naturally evolved catalytic properties. Consequently, our method, which combines automated protein translation with high-sensitivity and time-dependent detection of multiple products, provides a new approach to annotate glycoside hydrolase phylogenetic trees with functional measurements. PMID:26579511

  18. A study of ethanol reactions on O2-treated Au/TiO2. Effect of support and metal loading on reaction selectivity

    NASA Astrophysics Data System (ADS)

    Nadeem, M. A.; Waterhouse, G. I. N.; Idriss, H.

    2016-08-01

    The reactions of ethanol have been studied on bare and Au supported TiO2 polymorphs (anatase and rutile) in order to understand the effect of Au loading and prior O2 treatment on the reaction selectivity and conversion using temperature programmed desorption (TPD). Although O2 treatment has negligible effect on the reaction selectivity of ethanol on TiO2 alone it considerably affects the reaction on Au/TiO2. Au/TiO2 had three main effects on the reaction when compared to TiO2 alone. First, it switches the reaction selectivity of the dehydration (to ethylene) in favor of dehydrogenation (to acetaldehyde) on both polymorphs. Second, it decreases the desorption temperature of the main reaction products. Third, it increases secondary reaction products (mainly C4 (crotonaldehyde, butene, furan) reaching ca. 78% of the overall carbon selectivity for the 8 wt.% Au/TiO2 anatase. These effects are more pronounced on the anatase phase when compared to that on the rutile phase. Reasons for these are discussed.

  19. Reaction selectivity studies on nanolithographically-fabricated platinum model catalyst arrays

    SciTech Connect

    Grunes, Jeffrey Benjamin

    2004-05-15

    In an effort to understand the molecular ingredients of catalytic activity and selectivity toward the end of tuning a catalyst for 100% selectivity, advanced nanolithography techniques were developed and utilized to fabricate well-ordered two-dimensional model catalyst arrays of metal nanostructures on an oxide support for the investigation of reaction selectivity. In-situ and ex-situ surface science techniques were coupled with catalytic reaction data to characterize the molecular structure of the catalyst systems and gain insight into hydrocarbon conversion in heterogeneous catalysis. Through systematic variation of catalyst parameters (size, spacing, structure, and oxide support) and catalytic reaction conditions (hydrocarbon chain length, temperature, pressures, and gas composition), the data presented in this dissertation demonstrate the ability to direct a reaction by rationally adjusting, through precise control, the design of the catalyst system. Electron beam lithography (EBL) was employed to create platinum nanoparticles on an alumina (Al{sub 2}O{sub 3}) support. The Pt nanoparticle spacing (100-150-nm interparticle distance) was varied in these samples, and they were characterized using x-ray photoelectron spectroscopy (XPS), transmission electron microscopy (TEM), scanning electron microscopy (SEM), and atomic force microscopy (AFM), both before and after reactions. The TEM studies showed the 28-nm Pt nanoparticles with 100 and 150-nm interparticle spacing on alumina to be polycrystalline in nature, with crystalline sizes of 3-5 nm. The nanoparticle crystallites increased significantly after heat treatment. The nanoparticles were still mostly polycrystalline in nature, with 2-3 domains. The 28-nm Pt nanoparticles deposited on alumina were removed by the AFM tip in contact mode with a normal force of approximately 30 nN. After heat treatment at 500 C in vacuum for 3 hours, the AFM tip, even at 4000 nN, could not remove the platinum nanoparticles. The

  20. Fabrication of Ultrafine Soft-Matter Arrays by Selective Contact Thermochemical Reaction

    PubMed Central

    Cai, X.; Wang, Yue; Wang, Xiaowei; Ji, Junhui; Hong, Jian; Pan, Feng; Chen, Jitao; Xue, Mianqi

    2013-01-01

    Patterning of functional soft matters at different length scales is important for diverse research fields including cell biology, tissue engineering and medicinal science and the development of optics and electronics. Here we have further improved a simple but very efficient method, selective contact thermochemical reaction (SCTR), for patterning soft matters over large area with a sub-100 nm resolution. By selecting contact between different precursors through a topographically patterned PDMS stamp and subsequently any heating way for thermalchemical reaction, thermal-related soft matters can be patterned to form controllable micro or nano structures, even three-dimensional structures. The fine tunability and controllability of as-prepared micro and nano structures demonstrate this versatile approach a far wide range of uses than the merely academic.

  1. Single-Atom Catalyst of Platinum Supported on Titanium Nitride for Selective Electrochemical Reactions.

    PubMed

    Yang, Sungeun; Kim, Jiwhan; Tak, Young Joo; Soon, Aloysius; Lee, Hyunjoo

    2016-02-01

    As a catalyst, single-atom platinum may provide an ideal structure for platinum minimization. Herein, a single-atom catalyst of platinum supported on titanium nitride nanoparticles were successfully prepared with the aid of chlorine ligands. Unlike platinum nanoparticles, the single-atom active sites predominantly produced hydrogen peroxide in the electrochemical oxygen reduction with the highest mass activity reported so far. The electrocatalytic oxidation of small organic molecules, such as formic acid and methanol, also exhibited unique selectivity on the single-atom platinum catalyst. A lack of platinum ensemble sites changed the reaction pathway for the oxygen-reduction reaction toward a two-electron pathway and formic acid oxidation toward direct dehydrogenation, and also induced no activity for the methanol oxidation. This work demonstrates that single-atom platinum can be an efficient electrocatalyst with high mass activity and unique selectivity. PMID:26710326

  2. Multiple apolipoprotein kinetics measured in human HDL by high-resolution/accurate mass parallel reaction monitoring.

    PubMed

    Singh, Sasha A; Andraski, Allison B; Pieper, Brett; Goh, Wilson; Mendivil, Carlos O; Sacks, Frank M; Aikawa, Masanori

    2016-04-01

    Endogenous labeling with stable isotopes is used to study the metabolism of proteins in vivo. However, traditional detection methods such as GC/MS cannot measure tracer enrichment in multiple proteins simultaneously, and multiple reaction monitoring MS cannot measure precisely the low tracer enrichment in slowly turning-over proteins as in HDL. We exploited the versatility of the high-resolution/accurate mass (HR/AM) quadrupole Orbitrap for proteomic analysis of five HDL sizes. We identified 58 proteins in HDL that were shared among three humans and that were organized into five subproteomes according to HDL size. For seven of these proteins, apoA-I, apoA-II, apoA-IV, apoC-III, apoD, apoE, and apoM, we performed parallel reaction monitoring (PRM) to measure trideuterated leucine tracer enrichment between 0.03 to 1.0% in vivo, as required to study their metabolism. The results were suitable for multicompartmental modeling in all except apoD. These apolipoproteins in each HDL size mainly originated directly from the source compartment, presumably the liver and intestine. Flux of apolipoproteins from smaller to larger HDL or the reverse contributed only slightly to apolipoprotein metabolism. These novel findings on HDL apolipoprotein metabolism demonstrate the analytical breadth and scope of the HR/AM-PRM technology to perform metabolic research. PMID:26862155

  3. Monitoring, Modeling, and Diagnosis of Alkali-Silica Reaction in Small Concrete Samples

    SciTech Connect

    Agarwal, Vivek; Cai, Guowei; Gribok, Andrei V.; Mahadevan, Sankaran

    2015-09-01

    Assessment and management of aging concrete structures in nuclear power plants require a more systematic approach than simple reliance on existing code margins of safety. Structural health monitoring of concrete structures aims to understand the current health condition of a structure based on heterogeneous measurements to produce high-confidence actionable information regarding structural integrity that supports operational and maintenance decisions. This report describes alkali-silica reaction (ASR) degradation mechanisms and factors influencing the ASR. A fully coupled thermo-hydro-mechanical-chemical model developed by Saouma and Perotti by taking into consideration the effects of stress on the reaction kinetics and anisotropic volumetric expansion is presented in this report. This model is implemented in the GRIZZLY code based on the Multiphysics Object Oriented Simulation Environment. The implemented model in the GRIZZLY code is randomly used to initiate ASR in a 2D and 3D lattice to study the percolation aspects of concrete. The percolation aspects help determine the transport properties of the material and therefore the durability and service life of concrete. This report summarizes the effort to develop small-size concrete samples with embedded glass to mimic ASR. The concrete samples were treated in water and sodium hydroxide solution at elevated temperature to study how ingress of sodium ions and hydroxide ions at elevated temperature impacts concrete samples embedded with glass. Thermal camera was used to monitor the changes in the concrete sample and results are summarized.

  4. Long-Term Multiwaveband Monitoring of Selected Blazars (core Program)

    NASA Astrophysics Data System (ADS)

    The investigators request RXTE time to continue their long-term monitoring of the blazars 3C 279, PKS 1510-089, BL Lac, and 3C 273 2-3 times per week at radio, mm, IR, optical, X-ray, and, with the advent of GLAST, gamma-ray wavelengths. These, plus an added 5th object, CTA102, include blazars bright enough to detect strongly with RXTE and GLAST as well as to measure polarization on 7 mm VLBA images and at optical bands. By matching polarized features on VLBA images with variable polarization at optical bands and by associating X-ray and gamma-ray flares with similar events at these longer wavelengths, the investigators will locate where in the jet the emission occurs at all these wavebands. The relative timing of flares as a function of wavelength will overconstrain emission models.

  5. Unconventional application of the Mitsunobu reaction: Selective flavonolignan dehydration yielding hydnocarpins

    PubMed Central

    Huang, Guozheng; Schramm, Simon; Heilmann, Jörg; Biedermann, David; Křen, Vladimír

    2016-01-01

    Summary Various Mitsunobu conditions were investigated for a series of flavonolignans (silybin A, silybin B, isosilybin A, and silychristin A) to achieve either selective esterification in position C-23 or dehydration in a one-pot reaction yielding the biologically important enantiomers of hydnocarpin D, hydnocarpin and isohydnocarpin, respectively. This represents the only one-pot semi-synthetic method to access these flavonolignans in high yields. PMID:27340458

  6. Unconventional application of the Mitsunobu reaction: Selective flavonolignan dehydration yielding hydnocarpins.

    PubMed

    Huang, Guozheng; Schramm, Simon; Heilmann, Jörg; Biedermann, David; Křen, Vladimír; Decker, Michael

    2016-01-01

    Various Mitsunobu conditions were investigated for a series of flavonolignans (silybin A, silybin B, isosilybin A, and silychristin A) to achieve either selective esterification in position C-23 or dehydration in a one-pot reaction yielding the biologically important enantiomers of hydnocarpin D, hydnocarpin and isohydnocarpin, respectively. This represents the only one-pot semi-synthetic method to access these flavonolignans in high yields. PMID:27340458

  7. The Pressure Dependency of Stabilized Criegee Intermediate Yields of Selected Ozone-Alkene Reactions

    NASA Astrophysics Data System (ADS)

    Hakala, J. P.; Donahue, N. M.

    2014-12-01

    Stabilized Criegee Intermediates (SCI) play an important role as an oxidizing species in atmospheric reactions. The ozonolysis of alkenes in the atmosphere, i.e. the mechanism by which the SCIs are produced, is a major pathway to the formation of Secondary Organic Aerosols (SOA) in the atmosphere. Just how much SCIs contribute to the SOA formation is not well known and fundamental research in the kinetics of SCI formation need to be performed to shed light on this mystery. The alkene ozonolysis is highly exothermic reaction, so a third body is needed for stabilizing the SCI, thus making the SCI yield pressure dependent. We studied the production of SCIs at different pressures by studying their ability to oxidize sulfur dioxide in a pressure controlled flow reactor. We used a mixture of ultra-high purity nitrogen, oxygen, and a selective scavenger for hydroxyl radical (OH) as a carrier gas, and injected a mixture of nitrogen, sulfur dioxide and selected alkene to the center of the flow for ozonolysis to take place. With the OH radical scavenged, the SCI yield of the reaction was measured by measuring the amount of sulfuric acid formed in the reaction between SCI and sulfur dioxide with a Chemical Ionization Mass Spectrometer (CIMS). This work was supported by NASA/ROSES grant NNX12AE54G to CMU and Academy of Finland Center of Excellence project 1118615.

  8. Quantification of neurosteroids during pregnancy using selective ion monitoring mass spectrometry.

    PubMed

    Pennell, Kurt D; Woodin, Mark A; Pennell, Page B

    2015-03-01

    Analytical techniques used to quantify neurosteroids in biological samples are often compromised by non-specificity and limited dynamic range which can result in erroneous results. A relatively rapid and inexpensive gas chromatography-mass spectrometry (GC-MS) was developed to simultaneously measure nine neurosteroids, including allopregnanolone, estradiol, and progesterone, as well as 25-hydroxy-vitamin D3 in plasma samples collected from adult women subjects during and after pregnancy. Sample preparation involved solid-phase extraction and derivatization, followed by automated injection on a GC equipped with a mass selective detector (MSD) operated in single ion monitoring (SIM) mode to yield a run time of less than 11min. Method detection limits for all neurosteroids ranged from 30 to 200pg/mL (parts per trillion), with coefficients of variation that ranged from 3% to 5% based on intra-assay comparisons run in triplicate. Although concentrations of estradiol measured by chemiluminescent immunoassay (CIA) were consistent with values determined by GC-MS values, CIA yielded considerable higher values of progesterone, suggesting antibody cross reactions resulting from low specificity. Mean neurosteroid levels and representative time-course data demonstrate the ability of the method to quantify changes in multiple neurosteroids during pregnancy, including rapid declines in neurosteroid levels associated with delivery. This simplified GC-MS method holds particular promise for research and clinical laboratories that require simultaneous quantification of multiple neurosteroids, but lack the resources and expertise to support advanced liquid chromatography-tandem mass spectrometry facilities. PMID:25541057

  9. Quantification of Neurosteroids During Pregnancy Using Selective Ion Monitoring Mass Spectrometry

    PubMed Central

    Pennell, Kurt D.; Woodin, Mark A.; Pennell, Page B.

    2014-01-01

    Analytical techniques used to quantify neurosteroids in biological samples are often compromised by non-specificity and limited dynamic range which can result in erroneous results. A relatively rapid and inexpensive gas chromatography-mass spectrometry (GC-MS) was developed to simultaneously measure nine neurosteroids, including allopregnanolone, estradiol, and progesterone, as well as 25-hydroxy-vitamin D3 in plasma samples collected from adult women subjects during and after pregnancy. Sample preparation involved solid-phase extraction and derivatization, followed by automated injection on a GC equipped with a mass selective detector (MSD) operated in single ion monitoring (SIM) mode to yield a run time of less than 11 minutes. Method detection limits for all neurosteroids ranged from 30 to 200 pg/mL (parts per trillion), with coefficients of variation that ranged from 3 to 5% based on intra-assay comparisons run in triplicate. Although concentrations of estradiol measured by chemiluminescent immunoassay (CIA) were consistent with values determined by GC-MS values, CIA yielded considerable higher values of progesterone, suggesting antibody cross reactions resulting from low specificity. Mean neurosteroid levels and representative time-course data demonstrate the ability of the method to quantify changes in multiple neurosteroids during pregnancy, including rapid declines in neurosteroid levels associated with delivery. This simplified GC-MS method holds particular promise for research and clinical laboratories that require simultaneous quantification of multiple neurosteroids, but lack the resources and expertise to support advanced liquid chromatography-tandem mass spectrometry facilities. PMID:25541057

  10. The growing use of herbal medicines: issues relating to adverse reactions and challenges in monitoring safety

    PubMed Central

    Ekor, Martins

    2014-01-01

    The use of herbal medicinal products and supplements has increased tremendously over the past three decades with not less than 80% of people worldwide relying on them for some part of primary healthcare. Although therapies involving these agents have shown promising potential with the efficacy of a good number of herbal products clearly established, many of them remain untested and their use are either poorly monitored or not even monitored at all. The consequence of this is an inadequate knowledge of their mode of action, potential adverse reactions, contraindications, and interactions with existing orthodox pharmaceuticals and functional foods to promote both safe and rational use of these agents. Since safety continues to be a major issue with the use of herbal remedies, it becomes imperative, therefore, that relevant regulatory authorities put in place appropriate measures to protect public health by ensuring that all herbal medicines are safe and of suitable quality. This review discusses toxicity-related issues and major safety concerns arising from the use of herbal medicinal products and also highlights some important challenges associated with effective monitoring of their safety. PMID:24454289

  11. Quantitative Profiling of Long-Chain Bases by Mass Tagging and Parallel Reaction Monitoring

    PubMed Central

    Ejsing, Christer S.; Bilgin, Mesut; Fabregat, Andreu

    2015-01-01

    Long-chain bases (LCBs) are both intermediates in sphingolipid metabolism and potent signaling molecules that control cellular processes. To understand how regulation of sphingolipid metabolism and levels of individual LCB species impinge upon physiological and pathophysiological processes requires sensitive and specific assays for monitoring these molecules. Here we describe a shotgun lipidomics method for quantitative profiling of LCB molecules. The method employs a “mass-tag” strategy where LCBs are chemically derivatized with deuterated methyliodide (CD3I) to produce trimethylated derivatives having a positively charged quaternary amine group. This chemical derivatization minimizes unwanted in-source fragmentation of LCB analytes and prompts a characteristic trimethylaminium fragment ion that enables sensitive and quantitative profiling of LCB molecules by parallel reaction monitoring on a hybrid quadrupole time-of-flight mass spectrometer. Notably, the strategy provides, for the first time, a routine for monitoring endogenous 3-ketosphinganine molecules and distinguishing them from more abundant isomeric sphingosine molecules. To demonstrate the efficacy of the methodology we report an in-depth characterization of the LCB composition of yeast mutants with defective sphingolipid metabolism and the absolute levels of LCBs in mammalian cells. The strategy is generic, applicable to other types of mass spectrometers and can readily be applied as an additional routine in workflows for global lipidome quantification and for functional studies of sphingolipid metabolism. PMID:26660097

  12. Monitoring chemical reactions by low-field benchtop NMR at 45 MHz: pros and cons.

    PubMed

    Silva Elipe, Maria Victoria; Milburn, Robert R

    2016-06-01

    Monitoring chemical reactions is the key to controlling chemical processes where NMR can provide support. High-field NMR gives detailed structural information on chemical compounds and reactions; however, it is expensive and complex to operate. Conversely, low-field NMR instruments are simple and relatively inexpensive alternatives. While low-field NMR does not provide the detailed information as the high-field instruments as a result of their smaller chemical shift dispersion and the complex secondary coupling, it remains of practical value as a process analytical technology (PAT) tool and is complimentary to other established methods, such as ReactIR and Raman spectroscopy. We have tested a picoSpin-45 (currently under ThermoFisher Scientific) benchtop NMR instrument to monitor three types of reactions by 1D (1) H NMR: a Fischer esterification, a Suzuki cross-coupling, and the formation of an oxime. The Fischer esterification is a relatively simple reaction run at high concentration and served as proof of concept. The Suzuki coupling is an example of a more complex, commonly used reaction involving overlapping signals. Finally, the oxime formation involved a reaction in two phases that cannot be monitored by other PAT tools. Here, we discuss the pros and cons of monitoring these reactions at a low-field of 45 MHz by 1D (1) H NMR. Copyright © 2015 John Wiley & Sons, Ltd. PMID:25616193

  13. Rangeland assessment and monitoring methods guide - an interactive tool for selecting methods for assessment and monitoring

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A common concern expressed by land managers and biologists is that they do not know enough about the strengths and weaknesses of different field and remote-sensing methods for rangeland assessment and monitoring. The Methods Guide is a web-based tool and resource that provides researchers and manage...

  14. CRISPR/Cas9-Assisted Transformation-Efficient Reaction (CRATER) for Near-Perfect Selective Transformation

    NASA Technical Reports Server (NTRS)

    Rothschild, Lynn J.; Greenberg, Daniel T.; Takahashi, Jack R.; Thompson, Kirsten A.; Maheshwari, Akshay J.; Kent, Ryan E.; McCutcheon, Griffin; Shih, Joseph D.; Calvet, Charles; Devlin, Tyler D.; Ju, Tina; Kunin, Daniel; Lieberman, Erica; Nguyen, Thai; Tran, Forrest; Xiang, Daniel; Fujishima, Kosuke

    2015-01-01

    The CRISPR (Clustered, Regularly Interspaced, Short Palindromic Repeats)/Cas9 system has revolutionized genome editing by providing unprecedented DNA-targeting specificity. Here we demonstrate that this system can be also applied in vitro to fundamental cloning steps to facilitate efficient plasmid selection for transformation and selective gene insertion into plasmid vectors by cleaving unwanted plasmid byproducts with a single-guide RNA (sgRNA)-Cas9 nuclease complex. Using fluorescent and chromogenic proteins as reporters, we demonstrate that CRISPR/Cas9 cleavage excludes multiple plasmids as well as unwanted ligation byproducts resulting in an unprecedented increase in the transformation success rate from approximately 20% to nearly 100%. Thus, this CRISPR/Cas9-Assisted Transformation-Efficient Reaction (CRATER) protocol is a novel, inexpensive, and convenient application to conventional molecular cloning to achieve near-perfect selective transformation.

  15. Adverse drug reaction monitoring: support for pharmacovigilance at a tertiary care hospital in Northern Brazil

    PubMed Central

    2013-01-01

    Background Adverse drug reactions (ADRs) are recognised as a common cause of hospital admissions, and they constitute a significant economic burden for hospitals. Hospital-based ADR monitoring and reporting programmes aim to identify and quantify the risks associated with the use of drugs provided in a hospital setting. This information may be useful for identifying and minimising preventable ADRs and may enhance the ability of prescribers to manage ADRs more effectively. The main objectives of this study were to evaluate ADRs that occurred during inpatient stays at the Hospital Geral de Palmas (HGP) in Tocantins, Brazil, and to facilitate the development of a pharmacovigilance service. Methods A prospective study was conducted at HGP over a period of 8 months, from January 2009 to August 2009. This observational, cross-sectional, descriptive study was based on an analysis of medical records. Several parameters were utilised in the data evaluation, including patient demographics, drug and reaction characteristics, and reaction outcomes. The reaction severity and predisposing factors were also assessed. Results The overall incidence of ADRs in the patient population was 3.1%, and gender was not found to be a risk factor. The highest ADR rate (75.8%) was found in the adult age group 15 to 50 years, and the lowest ADR rate was found in children aged 3 to 13 years (7.4%). Because of the high frequency of ADRs in orthopaedic (25%), general medicine (22%), and oncology (16%) patients, improved control of the drugs used in these specialties is required. Additionally, the nurse team (52.7%) registered the most ADRs in medical records, most likely due to the job responsibilities of nurses. As expected, the most noticeable ADRs occurred in skin tissues, with such ADRs are more obvious to medical staff, with rashes being the most common reactions. Metamizole, tramadol, and vancomycin were responsible for 21, 11.6, and 8.4% of ADRs, respectively. The majority of ADRs had

  16. Cyanobacterial phycobilisomes: selective dissociation monitored by fluorescence and circular dichroism

    SciTech Connect

    Rigbi, M.; Rosinski, J.; Siegelman, H.W.; Sutherland, J.C.

    1980-04-01

    Phycobilisomes are supramolecular assemblies of phycobiliproteins responsible for photosynthetic light collection in red algae and cyanobacteria. They can be selectively dissociated by reduction of temperature and buffer concentration. Phycobilisomes isolated from Fremyella diplosiphon transfer energy collected by C-phycoerythrin and C-phycocyanin to allophycocyanin. The energy transfer to allophycocyanin is nearly abolished at 2/sup 0/C, as indicated by a blue shift in fluorescence emission, and is accompanied by a decrease in the circular dichroism in the region of allophycocyanin absorbance. Further dissociation of the phycobilisomes can be attained by reduction of buffer concentration and holding at 2/sup 0/C. Energy transfer to C-phycocyanin is nearly abolished, and decreases occur in the circular dichroism in the region of C-phycocyanin and C-phycoerythrin absorbance. Complete dissociation of the phycobilisomes at low buffer concentration and 2/sup 0/C requires extended time. Energy transfer to C-phycocyanin is further reduced and the circular dichroism maximum of C-phycoerythrin at 575 nm is lost. Circular dichroism provides information on the hexamer-monomer transitions of the phycobiliproteins, whereas fluorescence is indicative of hexamer-hexamer interactions. We consider that hydrophobic interactions are fundamental to the maintenance of the structure and function of phycobilisomes.

  17. SIC-BASED HYDROGEN SELECTIVE MEMBRANES FOR WATER-GAS-SHIFT REACTION

    SciTech Connect

    Paul K.T. Liu

    2003-12-01

    A hydrogen selective membrane as a membrane reactor (MR) can significantly improve the power generation efficiency with a reduced capital and operating cost for the waster-gas-shift reaction. Existing hydrogen selective ceramic membranes are not suitable for the proposed MR due to their poor hydrothermal stability. In this project we have focused on the development of innovative silicon carbide (SiC) based hydrogen selective membranes, which can potentially overcome this technical barrier. SiC macro-porous membranes have been successfully fabricated via extrusion of commercially available SiC powder. Also, an SiC hydrogen selective thin film was prepared via our CVD/I technique. This composite membrane demonstrated excellent hydrogen selectivity at high temperature ({approx}600 C). More importantly, this membrane also exhibited a much improved hydrothermal stability at 600 C with 50% steam (atmospheric pressure) for nearly 100 hours. In parallel, we have explored an alternative approach to develop a H{sub 2} selective SiC membrane via pyrolysis of selected pre-ceramic polymers and sol-gel techniques. Building upon the positive progress made in the membrane development study, we conducted an optimization study to develop an H{sub 2} selective SiC membrane with sufficient hydrothermal stability suitable for the WGS environment. In addition, mathematical simulation has been performed to compare the performance of the membrane reactor (MR) vs conventional packed bed reactor for WGS reaction. Our result demonstrates that >99.999% conversion can be accomplished via WGS-MR using the hydrogen selective membrane developed by us. Further, water/CO ratio can be reduced, and >97% hydrogen recovery and <200 ppm CO can be accomplished according to the mathematical simulation. Thus, we believe that the operating economics of WGS can be improved significantly based upon the proposed MR concept. In parallel, gas separations and hydrothermal and long-term-storage stability of the

  18. The proton transfer reaction mass spectrometer and its use in medical science: applications to drug assays and the monitoring of bacteria

    NASA Astrophysics Data System (ADS)

    Critchley, A.; Elliott, T. S.; Harrison, G.; Mayhew, C. A.; Thompson, J. M.; Worthington, T.

    2004-12-01

    Proton transfer reaction mass spectrometry (PTR-MS) enables monitoring of trace gases in air with high sensitivity without major gases interfering. In this paper, we present the potential use of a proton transfer reaction mass spectrometer for two medical applications; the monitoring of drugs and bacterial infection. The first study illustrates a feasibility trial to monitor the intravenous anaesthetic agent 2,6-di-isopropyl phenol (propofol), and two of its metabolites, on the breath of patients in real-time during surgery. Propofol is a commonly used intravenous anaesthetic. However, there is no method of instantaneously monitoring the plasma concentration of the agent during surgery, and therefore determining whether or not the plasma level is of such a value to ensure that the patient is correctly anaesthetized. That propofol and its metabolites were monitored in real-time using the PTR-MS suggests possibilities for routine intravenous anaesthesia monitoring analogous to that for volatile anaesthetic agents. In addition to the above work we also investigated proton transfer to another anaesthetic, sevoflurane. Comparisons between PTR-MS and selected ion flow tube (SIFT) investigations are presented. The second study presented in this paper investigated the volatile organic compounds emitted by microbial cell cultures. The objective was to show that different microbial cultures could be readily distinguished from the resulting mass spectra recorded using the PTR-MS. The initial results are encouraging, which taken together with the real-time analysis and high sensitivity of the PTR-MS, means that proton transfer reaction mass spectrometry has the potential to characterise bacterial infection rapidly.

  19. Reaction kinetics of selected micropollutants in ozonation and advanced oxidation processes.

    PubMed

    Jin, Xiaohui; Peldszus, Sigrid; Huck, Peter M

    2012-12-01

    Second-order reaction rate constants of micropollutants with ozone (k(O3)) and hydroxyl radicals (k(OH)) are essential for evaluating their removal efficiencies from water during ozonation and advanced oxidation processes. Kinetic data are unavailable for many of the emerging micropollutants. Twenty-four micropollutants with very diverse structures and applications including endocrine disrupting compounds, pharmaceuticals, and personal care products were selected, and their k(O3) and k(OH) values were determined using bench-scale reactors (at pH 7 and T = 20 °C). Reactions with molecular ozone are highly selective as indicated by their k(O3) values ranging from 10(-2)-10(7) M(-1) s(-1). The general trend of ozone reactivity can be explained by micropollutant structures in conjunction with the electrophilic nature of ozone reactions. All of the studied compounds are highly reactive with hydroxyl radicals as shown by their high k(OH) values (10(8)-10(10) M(-1) s(-1)) even though they are structurally very diverse. For compounds with a low reactivity toward ozone, hydroxyl radical based treatment such as O(3)/H(2)O(2) or UV/H(2)O(2) is a viable alternative. This study contributed to filling the data gap pertaining kinetic data of organic micropollutants while confirming results reported in the literature where available. PMID:23079129

  20. Development of a microspectrophotometer system for monitoring the redox reactions of respiratory pigments

    NASA Astrophysics Data System (ADS)

    Kavanagh, Karen Y.; Walsh, James E.; Murphy, J.; Harmey, M.; Farrell, M. A.; Hardimann, O.; Perryman, R.

    1997-05-01

    The continuing demand for non-invasive tools for use in clinical diagnosis has created the need for flexible and innovative optical systems which satisfy current requirements. We report the development of a microspectrophotometer system for use on mitochondrial respiratory pigments. This novel optical fiber set-up uses visible spectrophotometry to monitor the reduction of mitochondrial electron carriers. Preliminary data is presented for the reduction of cytochrome-c by two methods. In the first, cytochrome-c was reduced in isolation using sodium dithionite. The second was an in-vivo simulation of the reduction of cytochrome-c using the mitochondrial extract from rat liver. The key features of the system are; front end adaptability, high sensitivity and fast scanning capabilities which are essential for the rapid biological reactions which are observed.

  1. Detection, monitoring and modelling of alkali-aggregate reaction in Kouga Dam (South Africa)

    SciTech Connect

    Elges, H.; Lecocq, P.; Oosthuizen, C.; Geertsema, A.

    1995-12-31

    Kouga Dam (formerly Paul Sauer Dam) is a double curvature arch dam completed in 1969. The aggregates and the cement used for the construction have subsequently been proven to be alkali reactive. The results of the monitoring programme and the alkali-aggregate reaction (AAR) tests as well as the methodology developed to standardise the logging of cores for these investigations are presented. A brief description of the Finite Element Model used to approximate the AAR process in order to determine positions for in-situ stress measurements is also given. The aim with these tests is to refine the model for prediction of the long-term behaviour of the dam and to make an assessment of the possibility of raising the dam.

  2. The parallel reaction monitoring method contributes to a highly sensitive polyubiquitin chain quantification

    SciTech Connect

    Tsuchiya, Hikaru; Tanaka, Keiji Saeki, Yasushi

    2013-06-28

    Highlights: •The parallel reaction monitoring method was applied to ubiquitin quantification. •The ubiquitin PRM method is highly sensitive even in biological samples. •Using the method, we revealed that Ufd4 assembles the K29-linked ubiquitin chain. -- Abstract: Ubiquitylation is an essential posttranslational protein modification that is implicated in a diverse array of cellular functions. Although cells contain eight structurally distinct types of polyubiquitin chains, detailed function of several chain types including K29-linked chains has remained largely unclear. Current mass spectrometry (MS)-based quantification methods are highly inefficient for low abundant atypical chains, such as K29- and M1-linked chains, in complex mixtures that typically contain highly abundant proteins. In this study, we applied parallel reaction monitoring (PRM), a quantitative, high-resolution MS method, to quantify ubiquitin chains. The ubiquitin PRM method allows us to quantify 100 attomole amounts of all possible ubiquitin chains in cell extracts. Furthermore, we quantified ubiquitylation levels of ubiquitin-proline-β-galactosidase (Ub-P-βgal), a historically known model substrate of the ubiquitin fusion degradation (UFD) pathway. In wild-type cells, Ub-P-βgal is modified with ubiquitin chains consisting of 21% K29- and 78% K48-linked chains. In contrast, K29-linked chains are not detected in UFD4 knockout cells, suggesting that Ufd4 assembles the K29-linked ubiquitin chain(s) on Ub-P-βgal in vivo. Thus, the ubiquitin PRM is a novel, useful, quantitative method for analyzing the highly complicated ubiquitin system.

  3. Absolute state-selected total cross sections for the O(+)(4S) + CO2 reactions

    NASA Astrophysics Data System (ADS)

    Flesch, G. D.; Ng, C. Y.

    1991-12-01

    Results are presented on measurements of absolute state-selected total cross sections for O2(+), CO2(+), CO(+), and C(+) produced in the reaction between O(+)(4S) and CO2, which were conducted in the center-of-mass collision energy (Ecm) range of 0.2-150 eV. It was found that, with increasing collisional energy, the cross section of O2(+) dropped off rapidly and became essentially zero at Ecm above 3 eV. The dependence of O2(+) cross section on the Ecm is consistent with a collision complex mechanism for the reaction between O(+)(4S) and CO2 yielding CO2(+) + O. The values for O2(+) obtained in this experiment were significantly higher than those reported by Rutherford and Vroom (1976).

  4. Indicators for Monitoring Water, Sanitation, and Hygiene: A Systematic Review of Indicator Selection Methods.

    PubMed

    Schwemlein, Stefanie; Cronk, Ryan; Bartram, Jamie

    2016-03-01

    Monitoring water, sanitation, and hygiene (WaSH) is important to track progress, improve accountability, and demonstrate impacts of efforts to improve conditions and services, especially in low- and middle-income countries. Indicator selection methods enable robust monitoring of WaSH projects and conditions. However, selection methods are not always used and there are no commonly-used methods for selecting WaSH indicators. To address this gap, we conducted a systematic review of indicator selection methods used in WaSH-related fields. We present a summary of indicator selection methods for environment, international development, and water. We identified six methodological stages for selecting indicators for WaSH: define the purpose and scope; select a conceptual framework; search for candidate indicators; determine selection criteria; score indicators against criteria; and select a final suite of indicators. This summary of indicator selection methods provides a foundation for the critical assessment of existing methods. It can be used to inform future efforts to construct indicator sets in WaSH and related fields. PMID:26999180

  5. Indicators for Monitoring Water, Sanitation, and Hygiene: A Systematic Review of Indicator Selection Methods

    PubMed Central

    Schwemlein, Stefanie; Cronk, Ryan; Bartram, Jamie

    2016-01-01

    Monitoring water, sanitation, and hygiene (WaSH) is important to track progress, improve accountability, and demonstrate impacts of efforts to improve conditions and services, especially in low- and middle-income countries. Indicator selection methods enable robust monitoring of WaSH projects and conditions. However, selection methods are not always used and there are no commonly-used methods for selecting WaSH indicators. To address this gap, we conducted a systematic review of indicator selection methods used in WaSH-related fields. We present a summary of indicator selection methods for environment, international development, and water. We identified six methodological stages for selecting indicators for WaSH: define the purpose and scope; select a conceptual framework; search for candidate indicators; determine selection criteria; score indicators against criteria; and select a final suite of indicators. This summary of indicator selection methods provides a foundation for the critical assessment of existing methods. It can be used to inform future efforts to construct indicator sets in WaSH and related fields. PMID:26999180

  6. Monitoring transcranial direct current stimulation induced changes in cortical excitability during the serial reaction time task.

    PubMed

    Ambrus, Géza Gergely; Chaieb, Leila; Stilling, Roman; Rothkegel, Holger; Antal, Andrea; Paulus, Walter

    2016-03-11

    The measurement of the motor evoked potential (MEP) amplitudes using single pulse transcranial magnetic stimulation (TMS) is a common method to observe changes in motor cortical excitability. The level of cortical excitability has been shown to change during motor learning. Conversely, motor learning can be improved by using anodal transcranial direct current stimulation (tDCS). In the present study, we aimed to monitor cortical excitability changes during an implicit motor learning paradigm, a version of the serial reaction time task (SRTT). Responses from the first dorsal interosseous (FDI) and forearm flexor (FLEX) muscles were recorded before, during and after the performance of the SRTT. Online measurements were combined with anodal, cathodal or sham tDCS for the duration of the SRTT. Negative correlations between the amplitude of online FDI MEPs and SRTT reaction times (RTs) were observed across the learning blocks in the cathodal condition (higher average MEP amplitudes associated with lower RTs) but no significant differences in the anodal and sham conditions. tDCS did not have an impact on SRTT performance, as would be predicted based on previous studies. The offline before-after SRTT MEP amplitudes showed an increase after anodal and a tendency to decrease after cathodal stimulation, but these changes were not significant. The combination of different interventions during tDCS might result in reduced efficacy of the stimulation that in future studies need further attention. PMID:26826607

  7. Derivatization Strategy for the Comprehensive Characterization of Endogenous Fatty Aldehydes Using HPLC-Multiple Reaction Monitoring.

    PubMed

    Tie, Cai; Hu, Ting; Jia, Zhi-Xin; Zhang, Jin-Lan

    2016-08-01

    Fatty aldehydes are crucial substances that mediate a wide range of vital physiological functions, particularly lipid peroxidation. Fatty aldehydes such as acrolein and 4-hydroxynonenal (4-HNE) are considered potential biomarkers of myocardial ischemia and dementia, but analytical techniques for fatty aldehydes are lacking. In the present study, a comprehensive characterization strategy with high sensitivity and facility for fatty aldehydes based on derivatization and high-performance liquid chromatography-multiple reaction monitoring (HPLC-MRM) was developed. The fatty aldehydes of a biosample were derivatized using 2,4-bis(diethylamino)-6-hydrazino-1,3,5-triazine under mild and efficient reaction conditions at 37 °C for 15 min. The limit of detection (LOD) of the fatty aldehydes varied from 0.1 to 1 pg/mL, depending on the structures of these molecules. General MRM parameters were forged for the analysis of endogenous fatty aldehydes. "Heavy" derivatization reagents with 20 deuterium atoms were synthesized for both the discovery and comprehensive characterization of fatty aldehydes. More than 80 fatty aldehydes were detected in the biosamples. The new strategy was successfully implemented in global fatty aldehyde profiling of plasma and brain tissue of the bilateral common carotid artery (2VO) dementia rat model. Dozens of fatty aldehydes were significantly changed between the control and model groups. These findings further highlight the importance of endogenous fatty aldehydes. PMID:27397858

  8. Determination of Free Fatty Acids and Triglycerides by Gas Chromatography Using Selective Esterification Reactions

    SciTech Connect

    Kail, Brian W; Link, Dirk D; Morreale, Bryan D

    2012-11-01

    A method for selectively determining both free fatty acids (FFA) and triacylglycerides (TAGs) in biological oils was investigated and optimized using gas chromatography after esterification of the target species to their corresponding fatty acid methyl esters (FAMEs). The method used acid catalyzed esterification in methanolic solutions under conditions of varying severity to achieve complete conversion of more reactive FFAs while preserving the concentration of TAGs. Complete conversion of both free acids and glycerides to corresponding FAMEs was found to require more rigorous reaction conditions involving heating to 120°C for up to 2 h. Method validation was provided using gas chromatography–flame ionization detection, gas chromatography–mass spectrometry, and liquid chromatography–mass spectrometry. The method improves on existing methods because it allows the total esterified lipid to be broken down by FAMEs contributed by FFA compared to FAMEs from both FFA and TAGs. Single and mixed-component solutions of pure fatty acids and triglycerides, as well as a sesame oil sample to simulate a complex biological oil, were used to optimize the methodologies. Key parameters that were investigated included: HCl-to-oil ratio, temperature and reaction time. Pure free fatty acids were found to esterify under reasonably mild conditions (10 min at 50°C with a 2.1:1 HCl to fatty acid ratio) with 97.6 ± 2.3% recovery as FAMEs, while triglycerides were largely unaffected under these reaction conditions. The optimized protocol demonstrated that it is possible to use esterification reactions to selectively determine the free acid content, total lipid content, and hence, glyceride content in biological oils. This protocol also allows gas chromatography analysis of FAMEs as a more ideal analyte than glyceride species in their native state.

  9. Design of an Optical system for the In Situ Process Monitoring of Selective Laser Melting (SLM)

    NASA Astrophysics Data System (ADS)

    Lott, Philipp; Schleifenbaum, Henrich; Meiners, Wilhelm; Wissenbach, Konrad; Hinke, Christian; Bültmann, Jan

    Selective Laser Melting (SLM) is an Additive Manufacturing technology that enables the production of complex shaped individual parts with series identical mechanical properties. Areas of improvement are up to now quality and reproducibility of parts made by SLM due to different kinds of errors. Therefore the integration of a monitoring and control module into a SLM-machine is aspired. The design of such an optical system capable of monitoring high scanning velocities and melt pool dynamics is introduced as a first step.

  10. Advanced online monitoring of cell culture off-gas using proton transfer reaction mass spectrometry.

    PubMed

    Schmidberger, Timo; Gutmann, Rene; Bayer, Karl; Kronthaler, Jennifer; Huber, Robert

    2014-01-01

    Mass spectrometry has been frequently applied to monitor the O₂ and CO₂ content in the off-gas of animal cell culture fermentations. In contrast to classical mass spectrometry the proton transfer reaction mass spectrometry (PTR-MS) provides additional information of volatile organic compounds by application of a soft ionization technology. Hence, the spectra show less fragments and can more accurately assigned to particular compounds. In order to discriminate between compounds of non-metabolic and metabolic origin cell free experiments and fed-batch cultivations with a recombinant CHO cell line were conducted. As a result, in total eight volatiles showing high relevance to individual cultivation or cultivation conditions could be identified. Among the detected compounds methanethiol, with a mass-to-charge ratio of 49, qualifies as a key candidate in process monitoring due to its strong connectivity to lactate formation. Moreover, the versatile and complex data sets acquired by PTR MS provide a valuable resource for statistical modeling to predict non direct measurable parameters. Hence, partial least square regression was applied to the complete spectra of volatiles measured and important cell culture parameters such as viable cell density estimated (R²  = 0.86). As a whole, the results of this study clearly show that PTR-MS provides a powerful tool to improve bioprocess-monitoring for mammalian cell culture. Thus, specific volatiles emitted by cells and measured online by the PTR-MS and complex variables gained through statistical modeling will contribute to a deeper process understanding in the future and open promising perspectives to bioprocess control. PMID:24376199

  11. Tuning the selectivity of Gd3N cluster endohedral metallofullerene reactions with Lewis acids.

    PubMed

    Stevenson, Steven; Rottinger, Khristina A; Fahim, Muska; Field, Jessica S; Martin, Benjamin R; Arvola, Kristine D

    2014-12-15

    We demonstrate the manipulation of the Lewis acid strength to selectively fractionate different types of Gd3N metallofullerenes that are present in complex mixtures. Carbon disulfide is used for all Lewis acid studies. CaCl2 exhibits the lowest reactivity but the highest selectivity by precipitating only those gadolinium metallofullerenes with the lowest first oxidation potentials. ZnCl2 selectively complexes Gd3N@C88 during the first 4 h of reaction. Reaction with ZnCl2 for an additional 7 days permits a selective precipitation of Gd3N@C84 as the dominant endohedral isolated. A third fraction is the filtrate, which possesses Gd3N@C86 and Gd3N@C80 as the two dominant metallofullerenes. The order of increasing reactivity and decreasing selectivity (left to right) is as follows: CaCl2 < ZnCl2 < NiCl2 < MgCl2 < MnCl2 < CuCl2 < WCl4 ≪ WCl6 < ZrCl4 < AlCl3 < FeCl3. As a group, CaCl2, ZnCl2, and NiCl2 are the weakest Lewis acids and have the highest selectivity because of their very low precipitation onsets, which are below +0.19 V (i.e., endohedrals with first oxidation potentials below +0.19 V are precipitated). For CaCl2, the precipitation threshold is estimated at a remarkably low value of +0.06 V. Because most endohedrals possess first oxidation potentials significantly higher than +0.06 V, CaCl2 is especially useful in its ability to precipitate only a select group of gadolinium metallofullerenes. The Lewis acids of intermediate reactivity (i.e., precipitation onsets estimated between +0.19 and +0.4 V) are MgCl2, MnCl2, CuCl2, and WCl4. The strongest Lewis acids (WCl6, ZrCl4, AlCl3, and FeCl3) are the least selective and tend to precipitate the entire family of gadolinium metallofullerenes. Tuning the Lewis acid for a specific type of endohedral should be useful in a nonchromatographic purification method. The ability to control which metallofullerenes are permitted to precipitate and which endohedrals would remain in solution is a key outcome of this work. PMID

  12. Elucidation of Mechanisms and Selectivities of Metal-Catalyzed Reactions using Quantum Chemical Methodology.

    PubMed

    Santoro, Stefano; Kalek, Marcin; Huang, Genping; Himo, Fahmi

    2016-05-17

    Quantum chemical techniques today are indispensable for the detailed mechanistic understanding of catalytic reactions. The development of modern density functional theory approaches combined with the enormous growth in computer power have made it possible to treat quite large systems at a reasonable level of accuracy. Accordingly, quantum chemistry has been applied extensively to a wide variety of catalytic systems. A huge number of problems have been solved successfully, and vast amounts of chemical insights have been gained. In this Account, we summarize some of our recent work in this field. A number of examples concerned with transition metal-catalyzed reactions are selected, with emphasis on reactions with various kinds of selectivities. The discussed cases are (1) copper-catalyzed C-H bond amidation of indoles, (2) iridium-catalyzed C(sp(3))-H borylation of chlorosilanes, (3) vanadium-catalyzed Meyer-Schuster rearrangement and its combination with aldol- and Mannich-type additions, (4) palladium-catalyzed propargylic substitution with phosphorus nucleophiles, (5) rhodium-catalyzed 1:2 coupling of aldehydes and allenes, and finally (6) copper-catalyzed coupling of nitrones and alkynes to produce β-lactams (Kinugasa reaction). First, the methodology adopted in these studies is presented briefly. The electronic structure method in the great majority of these kinds of mechanistic investigations has for the last two decades been based on density functional theory. In the cases discussed here, mainly the B3LYP functional has been employed in conjunction with Grimme's empirical dispersion correction, which has been shown to improve the calculated energies significantly. The effect of the surrounding solvent is described by implicit solvation techniques, and the thermochemical corrections are included using the rigid-rotor harmonic oscillator approximation. The reviewed examples are chosen to illustrate the usefulness and versatility of the adopted methodology in

  13. Characterisation of hydrocarbonaceous overlayers important in metal-catalysed selective hydrogenation reactions

    NASA Astrophysics Data System (ADS)

    Lennon, David; Warringham, Robbie; Guidi, Tatiana; Parker, Stewart F.

    2013-12-01

    The hydrogenation of alkynes to alkenes over supported metal catalysts is an important industrial process and it has been shown that hydrocarbonaceous overlayers are important in controlling selectivity profiles of metal-catalysed hydrogenation reactions. As a model system, we have selected propyne hydrogenation over a commercial Pd(5%)/Al2O3 catalyst. Inelastic neutron scattering studies show that the C-H stretching mode ranges from 2850 to 3063 cm-1, indicating the mostly aliphatic nature of the overlayer and this is supported by the quantification of the carbon and hydrogen on the surface. There is also a population of strongly hydrogen-bonded hydroxyls, their presence would indicate that the overlayer probably contains some oxygen functionality. There is little evidence for any olefinic or aromatic species. This is distinctly different from the hydrogen-poor overlayers that are deposited on Ni/Al2O3 catalysts during methane reforming.

  14. Do candidate reactions relate to job performance or affect criterion-related validity? A multistudy investigation of relations among reactions, selection test scores, and job performance.

    PubMed

    McCarthy, Julie M; Van Iddekinge, Chad H; Lievens, Filip; Kung, Mei-Chuan; Sinar, Evan F; Campion, Michael A

    2013-09-01

    Considerable evidence suggests that how candidates react to selection procedures can affect their test performance and their attitudes toward the hiring organization (e.g., recommending the firm to others). However, very few studies of candidate reactions have examined one of the outcomes organizations care most about: job performance. We attempt to address this gap by developing and testing a conceptual framework that delineates whether and how candidate reactions might influence job performance. We accomplish this objective using data from 4 studies (total N = 6,480), 6 selection procedures (personality tests, job knowledge tests, cognitive ability tests, work samples, situational judgment tests, and a selection inventory), 5 key candidate reactions (anxiety, motivation, belief in tests, self-efficacy, and procedural justice), 2 contexts (industry and education), 3 continents (North America, South America, and Europe), 2 study designs (predictive and concurrent), and 4 occupational areas (medical, sales, customer service, and technological). Consistent with previous research, candidate reactions were related to test scores, and test scores were related to job performance. Further, there was some evidence that reactions affected performance indirectly through their influence on test scores. Finally, in no cases did candidate reactions affect the prediction of job performance by increasing or decreasing the criterion-related validity of test scores. Implications of these findings and avenues for future research are discussed. PMID:23937298

  15. Survivability and Abiotic Reactions of Selected Amino Acids in Different Hydrothermal System Simulators

    NASA Astrophysics Data System (ADS)

    Chandru, Kuhan; Imai, Eiichi; Kaneko, Takeo; Obayashi, Yumiko; Kobayashi, Kensei

    2013-04-01

    We tested the stability and reaction of several amino acids using hydrothermal system simulators: an autoclave and two kinds of flow reactors at 200-250 °C. This study generally showed that there is a variation in the individual amino acids survivability in the simulators. This is mainly attributed to the following factors; heat time, cold quenching exposure, metal ions and also silica. We observed that, in a rapid heating flow reactor, high aggregation and/or condensation of amino acids could occur even during a heat exposure of 2 min. We also monitored their stability in a reflow-type of simulator for 120 min at 20 min intervals. The non-hydrolyzed and hydrolyzed samples for this system showed a similar degradation only in the absence of metal ions.

  16. Method and apparatus for monitoring a hydrocarbon-selective catalytic reduction device

    DOEpatents

    Schmieg, Steven J; Viola, Michael B; Cheng, Shi-Wai S; Mulawa, Patricia A; Hilden, David L; Sloane, Thompson M; Lee, Jong H

    2014-05-06

    A method for monitoring a hydrocarbon-selective catalytic reactor device of an exhaust aftertreatment system of an internal combustion engine operating lean of stoichiometry includes injecting a reductant into an exhaust gas feedstream upstream of the hydrocarbon-selective catalytic reactor device at a predetermined mass flowrate of the reductant, and determining a space velocity associated with a predetermined forward portion of the hydrocarbon-selective catalytic reactor device. When the space velocity exceeds a predetermined threshold space velocity, a temperature differential across the predetermined forward portion of the hydrocarbon-selective catalytic reactor device is determined, and a threshold temperature as a function of the space velocity and the mass flowrate of the reductant is determined. If the temperature differential across the predetermined forward portion of the hydrocarbon-selective catalytic reactor device is below the threshold temperature, operation of the engine is controlled to regenerate the hydrocarbon-selective catalytic reactor device.

  17. Automatic identification approach for high-performance liquid chromatography-multiple reaction monitoring fatty acid global profiling.

    PubMed

    Tie, Cai; Hu, Ting; Jia, Zhi-Xin; Zhang, Jin-Lan

    2015-08-18

    Fatty acids (FAs) are a group of lipid molecules that are essential to organisms. As potential biomarkers for different diseases, FAs have attracted increasing attention from both biological researchers and the pharmaceutical industry. A sensitive and accurate method for globally profiling and identifying FAs is required for biomarker discovery. The high selectivity and sensitivity of high-performance liquid chromatography-multiple reaction monitoring (HPLC-MRM) gives it great potential to fulfill the need to identify FAs from complicated matrices. This paper developed a new approach for global FA profiling and identification for HPLC-MRM FA data mining. Mathematical models for identifying FAs were simulated using the isotope-induced retention time (RT) shift (IRS) and peak area ratios between parallel isotope peaks for a series of FA standards. The FA structures were predicated using another model based on the RT and molecular weight. Fully automated FA identification software was coded using the Qt platform based on these mathematical models. Different samples were used to verify the software. A high identification efficiency (greater than 75%) was observed when 96 FA species were identified in plasma. This FAs identification strategy promises to accelerate FA research and applications. PMID:26189701

  18. Mode- and bond-selected reactions of vibrationally excited methane and monodeuterated methane with chlorine atoms

    NASA Astrophysics Data System (ADS)

    Yoon, Sangwoon

    Direct infrared absorption prepares CH4 in two nearly isoenergetic vibrationally excited states, the symmetric stretch-bend combination (nu 1 + nu4) and the antisymmetric stretch-bend combination (nu3 + nu4), for a study of the effect of stretching vibrations of CH4 on the reaction, CH4 + Cl( 2P3/2) → CH3 + HCl. Comparison of intensities in the action spectra with those in the simulated absorption spectra shows that vibrational excitation of methane to the nu1 + nu4 state promotes the reaction more efficiently than excitation to the nu3 + nu4 state by a factor of 1.9 +/- 0.5. The reduced symmetry of CH3D allows us to explore the relative reactivity of the fundamental symmetric and the antisymmetric C-H stretches. We excite three vibrational eigenstates of CH3D near 3000 cm -1 that contain different amounts of symmetric C-H stretch (nu 1), antisymmetric C-H stretch (nu4), and two quanta of bend (2nu5). Analyzing the action spectra with the simulation and the composition of the eigenstates reveals that the nu1 vibration is 6 +/- 1 times more reactive than the nu4 vibration. Ab initio calculations of the vibrational eigenfunctions along the reaction coordinate show that as the Cl atom approaches, the nu1 vibration of CH3D is transformed into localized vibrational excitation in the C-H bond pointing toward the Cl atom, promoting the reaction, and the nu 4 vibrational energy flows into the distal C-H bonds that remain unaffected during the reaction, consistent with our experimental results. Selective vibrational excitation permits control of the outcome of a reaction with two competing channels. Vibrational excitation of the first overtone of C-D stretch (2nu2) of CH3D at ˜4300 cm-1 exclusively increases the probability of breaking the C-D bond, yielding CH3 but no CH2D. By contrast, excitation of the nu1 vibration, the nu4 vibration, or the combination vibration of C-H stretch and CH3 umbrella bend (nu4 + nu3) preferentially promotes the H-atom abstraction to

  19. STATISTICAL INFERENCE PROCEDURES FOR PROBABILITY SELECTION FUNCTIONS IN LONG-TERM MONITORING PROGRAMS

    EPA Science Inventory

    This report develops the theory and illustrates the use of selection functions to describe changes over time in the distributions of environmentally important variables at sites sampled as part of environmental monitoring programs. he first part of the report provides a review of...

  20. In situ and real-time monitoring of mechanochemical milling reactions using synchrotron X-ray diffraction.

    PubMed

    Halasz, Ivan; Kimber, Simon A J; Beldon, Patrick J; Belenguer, Ana M; Adams, Frank; Honkimäki, Veijo; Nightingale, Richard C; Dinnebier, Robert E; Friščić, Tomislav

    2013-09-01

    We describe the only currently available protocol for in situ, real-time monitoring of mechanochemical reactions and intermediates by X-ray powder diffraction. Although mechanochemical reactions (inducing transformations by mechanical forces such as grinding and milling) are normally performed in commercially available milling assemblies, such equipment does not permit direct reaction monitoring. We now describe the design and in-house modification of milling equipment that allows the reaction jars of the operating mill to be placed in the path of a high-energy (∼90 keV) synchrotron X-ray beam while the reaction is taking place. Resulting data are analyzed using conventional software, such as TOPAS. Reaction intermediates and products are identified using the Cambridge Structural Database or Inorganic Crystal Structure Database. Reactions are analyzed by fitting the time-resolved diffractograms using structureless Pawley refinement for crystalline phases that are not fully structurally characterized (such as porous frameworks with disordered guests), or the Rietveld method for solids with fully determined crystal structures (metal oxides, coordination polymers). PMID:23949378

  1. On-line monitoring of chemical reactions by using bench-top nuclear magnetic resonance spectroscopy.

    PubMed

    Danieli, E; Perlo, J; Duchateau, A L L; Verzijl, G K M; Litvinov, V M; Blümich, B; Casanova, F

    2014-10-01

    Real-time nuclear magnetic resonance (NMR) spectroscopy measurements carried out with a bench-top system installed next to the reactor inside the fume hood of the chemistry laboratory are presented. To test the system for on-line monitoring, a transfer hydrogenation reaction was studied by continuously pumping the reaction mixture from the reactor to the magnet and back in a closed loop. In addition to improving the time resolution provided by standard sampling methods, the use of such a flow setup eliminates the need for sample preparation. Owing to the progress in terms of field homogeneity and sensitivity now available with compact NMR spectrometers, small molecules dissolved at concentrations on the order of 1 mmol L(-1) can be characterized in single-scan measurements with 1 Hz resolution. Owing to the reduced field strength of compact low-field systems compared to that of conventional high-field magnets, the overlap in the spectrum of different NMR signals is a typical situation. The data processing required to obtain concentrations in the presence of signal overlap are discussed in detail, methods such as plain integration and line-fitting approaches are compared, and the accuracy of each method is determined. The kinetic rates measured for different catalytic concentrations show good agreement with those obtained with gas chromatography as a reference analytical method. Finally, as the measurements are performed under continuous flow conditions, the experimental setup and the flow parameters are optimized to maximize time resolution and signal-to-noise ratio. PMID:25111845

  2. Multiplexed Quantitation of Endogenous Proteins in Dried Blood Spots by Multiple Reaction Monitoring - Mass Spectrometry

    PubMed Central

    Chambers, Andrew G.; Percy, Andrew J.; Yang, Juncong; Camenzind, Alexander G.; Borchers, Christoph H.

    2013-01-01

    Dried blood spot (DBS) sampling, coupled with multiple reaction monitoring mass spectrometry (MRM-MS), is a well-established approach for quantifying a wide range of small molecule biomarkers and drugs. This sampling procedure is simpler and less-invasive than those required for traditional plasma or serum samples enabling collection by minimally trained personnel. Many analytes are stable in the DBS format without refrigeration, which reduces the cost and logistical challenges of sample collection in remote locations. These advantages make DBS sample collection desirable for advancing personalized medicine through population-wide biomarker screening. Here we expand this technology by demonstrating the first multiplexed method for the quantitation of endogenous proteins in DBS samples. A panel of 60 abundant proteins in human blood was targeted by monitoring proteotypic tryptic peptides and their stable isotope-labeled analogs by MRM. Linear calibration curves were obtained for 40 of the 65 peptide targets demonstrating multiple proteins can be quantitatively extracted from DBS collection cards. The method was also highly reproducible with a coefficient of variation of <15% for all 40 peptides. Overall, this assay quantified 37 proteins spanning a range of more than four orders of magnitude in concentration within a single 25 min LC/MRM-MS analysis. The protein abundances of the 33 proteins quantified in matching DBS and whole blood samples showed an excellent correlation, with a slope of 0.96 and an R2 value of 0.97. Furthermore, the measured concentrations for 80% of the proteins were stable for at least 10 days when stored at −20 °C, 4 °C and 37 °C. This work represents an important first step in evaluating the integration of DBS sampling with highly-multiplexed MRM for quantitation of endogenous proteins. PMID:23221968

  3. Estimating youth locomotion ground reaction forces using an accelerometer-based activity monitor.

    PubMed

    Neugebauer, Jennifer M; Hawkins, David A; Beckett, Laurel

    2012-01-01

    To address a variety of questions pertaining to the interactions between physical activity, musculoskeletal loading and musculoskeletal health/injury/adaptation, simple methods are needed to quantify, outside a laboratory setting, the forces acting on the human body during daily activities. The purpose of this study was to develop a statistically based model to estimate peak vertical ground reaction force (pVGRF) during youth gait. 20 girls (10.9 ± 0.9 years) and 15 boys (12.5 ± 0.6 years) wore a Biotrainer AM over their right hip. Six walking and six running trials were completed after a standard warm-up. Average AM intensity (g) and pVGRF (N) during stance were determined. Repeated measures mixed effects regression models to estimate pVGRF from Biotrainer activity monitor acceleration in youth (girls 10-12, boys 12-14 years) while walking and running were developed. Log transformed pVGRF had a statistically significant relationship with activity monitor acceleration, centered mass, sex (girl), type of locomotion (run), and locomotion type-acceleration interaction controlling for subject as a random effect. A generalized regression model without subject specific random effects was also developed. The average absolute differences between the actual and predicted pVGRF were 5.2% (1.6% standard deviation) and 9% (4.2% standard deviation) using the mixed and generalized models, respectively. The results of this study support the use of estimating pVGRF from hip acceleration using a mixed model regression equation. PMID:23133564

  4. Control of laser induced reactions in solids using selected photon energies and pulse pairs

    NASA Astrophysics Data System (ADS)

    Hess, Wayne; Joly, Alan; Beck, Kenneth; Gerrity, Daniel; Dickinson, J. Thomas; Sushko, Peter; Shluger, Alexander

    2002-03-01

    Laser control of reaction dynamics is an intensely studied area of chemical physics. Sophisticated quantum and optimal control schemes have been developed to overcome difficulties associated with rapid energy redistribution from laser-prepared initial states. Experiment and theory have demonstrated how specific product pathways can be selected by irradiation with one or more laser beams. Although most laser control research has focused on small gas-phase molecules, product and quantum state control of laser desorption from solids is possible using delayed pulse pairs, selected pulse duration or by judicious choice of laser wavelength. Theory indicates that it is possible to excite the surface of ionic crystals, over the bulk, using tunable laser sources.[1] We recently demonstrated control of ion emission from MgO surfaces[2] using femtosecond pulse pairs and nearly exclusive emission of hyperthermal Br (2P3/2) from laser excited KBr.[3] Here, we explore the mechanism of laser desorption in experiments using delayed pulse pairs and tunable single pulses. The first laser pulse induces formation of transient species and the second pulse then excites the intermediate state to induce desorption of selected species or quantum states. Selective desorption raises the intriguing prospect of selective surface modification. The principles described here should be extendable to other alkali halides and metal oxides. References: [1] A.L. Shluger, P.V. Sushko, and L.N. Kantorovich, Phys. Rev. B. 59, (1999) 2417. [2] K.M. Beck, A.G. Joly, and W.P. Hess, Sur. Sci. 451, 166 (2000). [3] W. P. Hess, A. G. Joly, K. M. Beck, D. P. Gerrity, P. V. Sushko, and A. L. Shluger, J. Chem. Phys. 115, 9463 (2001).

  5. MONITORING POTENTIAL DRUG INTERACTIONS AND REACTIONS VIA NETWORK ANALYSIS OF INSTAGRAM USER TIMELINES.

    PubMed

    Correia, Rion Brattig; Li, Lang; Rocha, Luis M

    2016-01-01

    Much recent research aims to identify evidence for Drug-Drug Interactions (DDI) and Adverse Drug reactions (ADR) from the biomedical scientific literature. In addition to this "Bibliome", the universe of social media provides a very promising source of large-scale data that can help identify DDI and ADR in ways that have not been hitherto possible. Given the large number of users, analysis of social media data may be useful to identify under-reported, population-level pathology associated with DDI, thus further contributing to improvements in population health. Moreover, tapping into this data allows us to infer drug interactions with natural products-including cannabis-which constitute an array of DDI very poorly explored by biomedical research thus far. Our goal is to determine the potential of Instagram for public health monitoring and surveillance for DDI, ADR, and behavioral pathology at large. Most social media analysis focuses on Twitter and Facebook, but Instagram is an increasingly important platform, especially among teens, with unrestricted access of public posts, high availability of posts with geolocation coordinates, and images to supplement textual analysis. Using drug, symptom, and natural product dictionaries for identification of the various types of DDI and ADR evidence, we have collected close to 7000 user timelines spanning from October 2010 to June 2015.We report on 1) the development of a monitoring tool to easily observe user-level timelines associated with drug and symptom terms of interest, and 2) population-level behavior via the analysis of co-occurrence networks computed from user timelines at three different scales: monthly, weekly, and daily occurrences. Analysis of these networks further reveals 3) drug and symptom direct and indirect associations with greater support in user timelines, as well as 4) clusters of symptoms and drugs revealed by the collective behavior of the observed population. This demonstrates that Instagram

  6. MONITORING POTENTIAL DRUG INTERACTIONS AND REACTIONS VIA NETWORK ANALYSIS OF INSTAGRAM USER TIMELINES

    PubMed Central

    CORREIA, RION BRATTIG; LI, LANG; ROCHA, LUIS M.

    2015-01-01

    Much recent research aims to identify evidence for Drug-Drug Interactions (DDI) and Adverse Drug reactions (ADR) from the biomedical scientific literature. In addition to this “Bibliome”, the universe of social media provides a very promising source of large-scale data that can help identify DDI and ADR in ways that have not been hitherto possible. Given the large number of users, analysis of social media data may be useful to identify under-reported, population-level pathology associated with DDI, thus further contributing to improvements in population health. Moreover, tapping into this data allows us to infer drug interactions with natural products—including cannabis—which constitute an array of DDI very poorly explored by biomedical research thus far. Our goal is to determine the potential of Instagram for public health monitoring and surveillance for DDI, ADR, and behavioral pathology at large. Most social media analysis focuses on Twitter and Facebook, but Instagram is an increasingly important platform, especially among teens, with unrestricted access of public posts, high availability of posts with geolocation coordinates, and images to supplement textual analysis. Using drug, symptom, and natural product dictionaries for identification of the various types of DDI and ADR evidence, we have collected close to 7000 user timelines spanning from October 2010 to June 2015. We report on 1) the development of a monitoring tool to easily observe user-level timelines associated with drug and symptom terms of interest, and 2) population-level behavior via the analysis of co-occurrence networks computed from user timelines at three different scales: monthly, weekly, and daily occurrences. Analysis of these networks further reveals 3) drug and symptom direct and indirect associations with greater support in user timelines, as well as 4) clusters of symptoms and drugs revealed by the collective behavior of the observed population. This demonstrates that

  7. Model selection and change detection for a time-varying mean in process monitoring

    NASA Astrophysics Data System (ADS)

    Burr, Tom; Hamada, Michael S.; Ticknor, Larry; Weaver, Brian

    2014-07-01

    Process monitoring (PM) for nuclear safeguards sometimes requires estimation of thresholds corresponding to small false alarm rates. Threshold estimation is an old topic; however, because possible new roles for PM are being evaluated in nuclear safeguards, it is timely to consider modern model selection options in the context of alarm threshold estimation. One of the possible new PM roles involves PM residuals, where a residual is defined as residual=data-prediction. This paper briefly reviews alarm threshold estimation, introduces model selection options, and considers several assumptions regarding the data-generating mechanism for PM residuals. Four PM examples from nuclear safeguards are included. One example involves frequent by-batch material balance closures where a dissolution vessel has time-varying efficiency, leading to time-varying material holdup. Another example involves periodic partial cleanout of in-process inventory, leading to challenging structure in the time series of PM residuals. Our main focus is model selection to select a defensible model for normal behavior with a time-varying mean in a PM residual stream. We use approximate Bayesian computation to perform the model selection and parameter estimation for normal behavior. We then describe a simple lag-one-differencing option similar to that used to monitor non-stationary times series to monitor for off-normal behavior.

  8. Site selectivity in the reaction of Si(111)-(7 times 7) with Si sub 2 H sub 6

    SciTech Connect

    Avouris, Ph.; Bozso, F. )

    1990-03-22

    We find that the reaction of disilane with the Si(111)-(7{times}7) surface shows strong site selectivity. The reaction involves the fission of the Si-Si bond of Si{sub 2}H{sub 6} even at low temperatures and occurs preferentially at rest-atom sites of the 7{times}7 surface. The reaction of the products of the thermal dissociation of the surface-bound SiH{sub x} groups with surface dangling-bond sites is also site selective. We propose mechanisms to explain the above observations.

  9. Medium-Ring Effects on the Endo/Exo Selectivity of the Organocatalytic Intramolecular Diels-Alder Reaction.

    PubMed

    Hooper, Joel F; James, Natalie C; Bozkurt, Esra; Aviyente, Viktorya; White, Jonathan M; Holland, Mareike C; Gilmour, Ryan; Holmes, Andrew B; Houk, K N

    2015-12-18

    The intramolecular Diels-Alder reaction has been used as a powerful method to access the tricyclic core of the eunicellin natural products from a number of 9-membered-ring precursors. The endo/exo selectivity of this reaction can be controlled through a remarkable organocatalytic approach, employing MacMillan's imidazolidinone catalysts, although the mechanistic origin of this selectivity remains unclear. We present a combined experimental and density functional theory investigation, providing insight into the effects of medium-ring constraints on the organocatalyzed intramolecular Diels-Alder reaction to form the isobenzofuran core of the eunicellins. PMID:26560246

  10. Structure sensitive selectivity of the NO-CO reaction over rhodium single crystal catalysts

    SciTech Connect

    Peden, C.H.F.; Belton, D.N.; Schmieg, S.J.

    1995-05-01

    The control of automotive emissions of nitrogen oxides (NO{sub x}) in passenger cars is accomplished by a heavy reliance on after-treatment of the engine exhaust using catalytic converters that contain a mixture of platinum (Pt), rhodium (Rh), and sometimes palladium (Pd). In this paper we examine the effect of surface structure on the NO-CO activity and selectivity by comparing the reactivity of Rh(110) and Rh(111) single crystal catalysts. Selectivity for the two possible nitrogen containing products from NO reduction, N{sub 2}O and N{sub 2}, is particularly interesting. Here we report that the selectivity of the NO-CO reaction is quite sensitive to the structure of the Rh catalyst metal surface. (A more complete description of these studies will be published elsewhere.) The more open Rh(110) surface tends to make significantly less N{sub 2}O than Rh(111) under virtually all conditions that we probed with these experiments. Furthermore, under the conditions used in this study, the NO-CO activity over Rh(110), as measured by the rate of NO loss, is somewhat faster than over Rh(111) with a lower apparent activation energy (Ea), 27.6 vs. 35.4 kcal/mol. We attribute these results to the greater tendency of the more open (110) surface to dissociate NO. Notably, more facile NO dissociation on Rh(110) would lead to greater steady-state concentrations of adsorbed N-atoms; thus, the (110) surface favors N-atom recombination over the surface reaction between adsorbed NO and N-atoms to make N{sub 2}O. In support of this, post-reaction surface analysis shows only NO on the Rh(111) surface while the Rh(110) surface contains predominantly N-atoms and much lower concentrations of adsorbed NO. NO dissociation on Rh(110) is more favorable than on Rh(111), in part, because it is less-severely poisoned by high surface concentrations of NO. In addition, the more-open (110) surface may be intrinsically more active for the elementary process of dissociating adsorbed NO.