Sample records for reaction monitoring mrm

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

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


    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. Quantitation of human milk proteins and their glycoforms using multiple reaction monitoring (MRM).

    Huang, Jincui; Kailemia, Muchena J; Goonatilleke, Elisha; Parker, Evan A; Hong, Qiuting; Sabia, Rocchina; Smilowitz, Jennifer T; German, J Bruce; Lebrilla, Carlito B


    Human milk plays a substantial role in the child growth, development and determines their nutritional and health status. Despite the importance of the proteins and glycoproteins in human milk, very little quantitative information especially on their site-specific glycosylation is known. As more functions of milk proteins and other components continue to emerge, their fine-detailed quantitative information is becoming a key factor in milk research efforts. The present work utilizes a sensitive label-free MRM method to quantify seven milk proteins (α-lactalbumin, lactoferrin, secretory immunoglobulin A, immunoglobulin G, immunoglobulin M, α1-antitrypsin, and lysozyme) using their unique peptides while at the same time, quantifying their site-specific N-glycosylation relative to the protein abundance. The method is highly reproducible, has low limit of quantitation, and accounts for differences in glycosylation due to variations in protein amounts. The method described here expands our knowledge about human milk proteins and provides vital details that could be used in monitoring the health of the infant and even the mother. Graphical Abstract The glycopeptides EICs generated from QQQ.

  3. A multiple reaction monitoring (MRM method to detect Bcr-Abl kinase activity in CML using a peptide biosensor.

    Tzu-Yi Yang

    Full Text Available The protein kinase Bcr-Abl plays a major role in the pathogenesis of chronic myelogenous leukemia (CML, and is the target of the breakthrough drug imatinib (Gleevec™. While most patients respond well to imatinib, approximately 30% never achieve remission or develop resistance within 1-5 years of starting imatinib treatment. Evidence from clinical studies suggests that achieving at least 50% inhibition of a patient's Bcr-Abl kinase activity (relative to their level at diagnosis is associated with improved patient outcomes, including reduced occurrence of resistance and longer maintenance of remission. Accordingly, sensitive assays for detecting Bcr-Abl kinase activity compatible with small amounts of patient material are desirable as potential companion diagnostics for imatinib. Here we report the detection of Bcr-Abl activity and inhibition by imatinib in the human CML cell line K562 using a cell-penetrating peptide biosensor and multiple reaction monitoring (MRM on a triple quadrupole mass spectrometer. MRM enabled reproducible, selective detection of the peptide biosensor at fmol levels from aliquots of cell lysate equivalent to ~15,000 cells. This degree of sensitivity will facilitate the miniaturization of the entire assay procedure down to cell numbers approaching 15,000, making it practical for translational applications in patient cells in which the limited amount of available patient material often presents a major challenge.

  4. A Focused Multiple Reaction Monitoring (MRM Quantitative Method for Bioactive Grapevine Stilbenes by Ultra-High-Performance Liquid Chromatography Coupled to Triple-Quadrupole Mass Spectrometry (UHPLC-QqQ

    Elías Hurtado-Gaitán


    Full Text Available Grapevine stilbenes are a family of polyphenols which derive from trans-resveratrol having antifungal and antimicrobial properties, thus being considered as phytoalexins. In addition to their diverse bioactive properties in animal models, they highlight a strong potential in human health maintenance and promotion. Due to this relevance, highly-specific qualitative and quantitative methods of analysis are necessary to accurately analyze stilbenes in different matrices derived from grapevine. Here, we developed a rapid, sensitive, and specific analysis method using ultra-high-performance liquid chromatography coupled to triple-quadrupole mass spectrometry (UHPLC-QqQ in MRM mode to detect and quantify five grapevine stilbenes, trans-resveratrol, trans-piceid, trans-piceatannol, trans-pterostilbene, and trans-ε-viniferin, whose interest in relation to human health is continuously growing. The method was optimized to minimize in-source fragmentation of piceid and to avoid co-elution of cis-piceid and trans-resveratrol, as both are detected with resveratrol transitions. The applicability of the developed method of stilbene analysis was tested successfully in different complex matrices including cellular extracts of Vitis vinifera cell cultures, reaction media of biotransformation assays, and red wine.

  5. An alpha-synuclein MRM assay with diagnostic potential for Parkinson's disease and monitoring disease progression

    Yang, Li [Department of Pathology, University of Washington, Seattle WA USA; Stewart, Tessandra [Department of Pathology, University of Washington, Seattle WA USA; Shi, Min [Department of Pathology, University of Washington, Seattle WA USA; Pottiez, Gwenael [Department of Pathology, University of Washington, Seattle WA USA; Dator, Romel [Department of Pathology, University of Washington, Seattle WA USA; Wu, Rui [Department of Pathology, University of Washington, Seattle WA USA; Department of Pathology, No. 3 Hospital of Beijing University, Beijing China; Aro, Patrick [Department of Pathology, University of Washington, Seattle WA USA; Schuster, Robert J. [Department of Pathology, University of Washington, Seattle WA USA; Ginghina, Carmen [Department of Pathology, University of Washington, Seattle WA USA; Pan, Catherine [Department of Pathology, University of Washington, Seattle WA USA; Gao, Yuqian [Pacific Northwest National Laboratory, Richland WA USA; Qian, Weijun [Pacific Northwest National Laboratory, Richland WA USA; Zabetian, Cyrus P. [Parkinson' s Disease Research and Geriatric Research, Education and Clinical Center, Veterans Affairs Puget Sound Health Care System, Seattle WA USA; Department of Neurology, University of Washington School of Medicine, Seattle WA USA; Hu, Shu-Ching [Department of Neurology, University of Washington School of Medicine, Seattle WA USA; Quinn, Joseph F. [Department of Neurology, Oregon Health and Science University, Portland OR USA; Zhang, Jing [Department of Pathology, University of Washington, Seattle WA USA; Department of Pathology, Peking University Health Science Centre and Third Hospital, Beijing 100083 China


    Aim: The alpha-synuclein (α-syn) level in human cerebrospinal fluid (CSF), as measured by immunoassays, is promising as a Parkinson’s disease (PD) biomarker. However, the levels of total α-syn are inconsistent among studies with large cohorts and different measurement platforms. Total α-syn level also does not correlate with disease severity or progression. Here, we developed a highly sensitive Multiple Reaction Monitoring (MRM) method to measure absolute CSF α-syn peptide concentrations without prior enrichment or fractionation, aiming to discover new candidate biomarkers. Results: Six peptides covering 73% of protein sequence were reliably identified, and two were consistently quantified in cross-sectional and longitudinal cohorts. Absolute concentration of α-syn in human CSF was determined to be 2.1ng/mL. A unique α-syn peptide, TVEGAGSIAAATGFVK (81-96), displayed excellent correlation with previous immunoassay results in two independent PD cohorts (p < 0.001), correlated with disease severity, and its changes significantly tracked the disease progression longitudinally. Conclusions: An MRM assay to quantify human CSF α-syn was developed and optimized. Sixty clinical samples from cross-sectional and longitudinal PD cohorts were analyzed with this approach. Although further larger-scale validation is needed, the results suggest that α-syn peptide could serve as a promising biomarker in PD diagnosis and progression.

  6. MaRiMba: A Software Application for Spectral Library-Based MRM Transition List Assembly

    Sherwood, Carly A.; Eastham, Ashley; Lee, Lik Wee; Peterson, Amelia; Eng, Jimmy K.; Shteynberg, David; Mendoza, Luis; Deutsch, Eric W.; Risler, Jenni; Tasman, Natalie; Aebersold, Ruedi; Lam, Henry; Martin, Daniel B


    Multiple reaction monitoring mass spectrometry (MRM-MS) is a targeted analysis method that has been increasingly viewed as an avenue to explore proteomes with unprecedented sensitivity and throughput. We have developed a software tool, called MaRiMba, to automate the creation of explicitly defined MRM transition lists required to program triple quadrupole mass spectrometers in such analyses. MaRiMba creates MRM transition lists from downloaded or custom-built spectral libraries, restricts out...

  7. MR Mammography (MRM). MR-Mammographie (MRM)

    Kaiser, W.A. (Radiologische Universitaetsklinik Bonn (Germany))


    MR mammography is carried out using a special breast coil. Gd-DTPA is injected as a contrast medium. Gradient-echo sequences are superior to the formerly used spin-echo sequences in that they show a greater sensitivity to contrast media. After the advent of gradient-echo sequences, the 0.2 mmol/kg dose that used to be injected in connection with spin-echo sequences was regarded as being too high. The best results were then achieved with 0.1 mmol/kg injections amounting to no more than 50% of the former dose. Provided that magnetic resonance imaging of the breast is carried out using the spexial examination technique discussed here, it may justly be described as magnetic resonance mammography (MRM). MR criteria are defined for such conditions as carcinoma, fibroadenoma, scars, mastopathy and cysts. (GDG).

  8. The application of multiple reaction monitoring and multi-analyte profiling to HDL proteins


    Background HDL carries a rich protein cargo and examining HDL protein composition promises to improve our understanding of its functions. Conventional mass spectrometry methods can be lengthy and difficult to extend to large populations. In addition, without prior enrichment of the sample, the ability of these methods to detect low abundance proteins is limited. Our objective was to develop a high-throughput approach to examine HDL protein composition applicable to diabetes and cardiovascular disease (CVD). Methods We optimized two multiplexed assays to examine HDL proteins using a quantitative immunoassay (Multi-Analyte Profiling- MAP) and mass spectrometric-based quantitative proteomics (Multiple Reaction Monitoring-MRM). We screened HDL proteins using human xMAP (90 protein panel) and MRM (56 protein panel). We extended the application of these two methods to HDL isolated from a group of participants with diabetes and prior cardiovascular events and a group of non-diabetic controls. Results We were able to quantitate 69 HDL proteins using MAP and 32 proteins using MRM. For several common proteins, the use of MRM and MAP was highly correlated (p HDL. On the other hand, MRM allowed the examination of several HDL proteins not available by MAP. Conclusions MAP and MRM offer a sensitive and high-throughput approach to examine changes in HDL proteins in diabetes and CVD. This approach can be used to measure the presented HDL proteins in large clinical studies. PMID:24397693

  9. MaRiMba: a software application for spectral library-based MRM transition list assembly.

    Sherwood, Carly A; Eastham, Ashley; Lee, Lik Wee; Peterson, Amelia; Eng, Jimmy K; Shteynberg, David; Mendoza, Luis; Deutsch, Eric W; Risler, Jenni; Tasman, Natalie; Aebersold, Ruedi; Lam, Henry; Martin, Daniel B


    Multiple reaction monitoring mass spectrometry (MRM-MS) is a targeted analysis method that has been increasingly viewed as an avenue to explore proteomes with unprecedented sensitivity and throughput. We have developed a software tool, called MaRiMba, to automate the creation of explicitly defined MRM transition lists required to program triple quadrupole mass spectrometers in such analyses. MaRiMba creates MRM transition lists from downloaded or custom-built spectral libraries, restricts output to specified proteins or peptides, and filters based on precursor peptide and product ion properties. MaRiMba can also create MRM lists containing corresponding transitions for isotopically heavy peptides, for which the precursor and product ions are adjusted according to user specifications. This open-source application is operated through a graphical user interface incorporated into the Trans-Proteomic Pipeline, and it outputs the final MRM list to a text file for upload to MS instruments. To illustrate the use of MaRiMba, we used the tool to design and execute an MRM-MS experiment in which we targeted the proteins of a well-defined and previously published standard mixture.

  10. A Targeted MRM Approach for Tempo-Spatial Proteomics Analyses.

    Moradian, Annie; Porras-Yakushi, Tanya R; Sweredoski, Michael J; Hess, Sonja


    When deciding to perform a quantitative proteomics analysis, selectivity, sensitivity, and reproducibility are important criteria to consider. The use of multiple reaction monitoring (MRM) has emerged as a powerful proteomics technique in that regard since it avoids many of the problems typically observed in discovery-based analyses. A prerequisite for such a targeted approach is that the protein targets are known, either as a result of previous global proteomics experiments or because a specific hypothesis is to be tested. When guidelines that have been established in the pharmaceutical industry many decades ago are taken into account, setting up an MRM assay is relatively straightforward. Typically, proteotypic peptides with favorable mass spectrometric properties are synthesized with a heavy isotope for each protein that is to be monitored. Retention times and calibration curves are determined using triple-quadrupole mass spectrometers. The use of iRT peptide standards is both recommended and fully integrated into the bioinformatics pipeline. Digested biological samples are mixed with the heavy and iRT standards and quantified. Here we present a generic protocol for the development of an MRM assay.

  11. MR mammography (MRM)

    Kaiser, W.A.


    The book deals with MRI for the diagnostic evaluation of malignant breast lesions. A survey of methods available for breast examination, magnetic resonance mammography (MRM) is briefly explained in terms of development and technical problems encountered in the various examinations. The clinical aspects from a central part of the book, giving information relating to the various neoplasms and a comprehensive review of cases. The book concludes with a chapter discussing the interpretation of data and images, presenting examples of normal findings and of manifestations of carcinoma, fibroadenoma, cysts, mastopathies, scars due to plastic surgery, and the lactating breast. (UWA). 648 figs., 25 tabs.

  12. Optimized Protocol for Quantitative Multiple Reaction Monitoring-Based Proteomic Analysis of Formalin-Fixed, Paraffin-Embedded Tissues.

    Kennedy, Jacob J; Whiteaker, Jeffrey R; Schoenherr, Regine M; Yan, Ping; Allison, Kimberly; Shipley, Melissa; Lerch, Melissa; Hoofnagle, Andrew N; Baird, Geoffrey Stuart; Paulovich, Amanda G


    Despite a clinical, economic, and regulatory imperative to develop companion diagnostics, precious few new biomarkers have been successfully translated into clinical use, due in part to inadequate protein assay technologies to support large-scale testing of hundreds of candidate biomarkers in formalin-fixed paraffin-embedded (FFPE) tissues. Although the feasibility of using targeted, multiple reaction monitoring mass spectrometry (MRM-MS) for quantitative analyses of FFPE tissues has been demonstrated, protocols have not been systematically optimized for robust quantification across a large number of analytes, nor has the performance of peptide immuno-MRM been evaluated. To address this gap, we used a test battery approach coupled to MRM-MS with the addition of stable isotope-labeled standard peptides (targeting 512 analytes) to quantitatively evaluate the performance of three extraction protocols in combination with three trypsin digestion protocols (i.e., nine processes). A process based on RapiGest buffer extraction and urea-based digestion was identified to enable similar quantitation results from FFPE and frozen tissues. Using the optimized protocols for MRM-based analysis of FFPE tissues, median precision was 11.4% (across 249 analytes). There was excellent correlation between measurements made on matched FFPE and frozen tissues, both for direct MRM analysis (R(2) = 0.94) and immuno-MRM (R(2) = 0.89). The optimized process enables highly reproducible, multiplex, standardizable, quantitative MRM in archival tissue specimens.

  13. Precision of multiple reaction monitoring mass spectrometry analysis of formalin-fixed, paraffin-embedded tissue.

    Sprung, Robert W; Martinez, Misti A; Carpenter, Kristen L; Ham, Amy-Joan L; Washington, Mary Kay; Arteaga, Carlos L; Sanders, Melinda E; Liebler, Daniel C


    We compared the reproducibility of multiple reaction monitoring (MRM) mass spectrometry-based peptide quantitation in tryptic digests from formalin-fixed, paraffin-embedded (FFPE) and frozen clear cell renal cell carcinoma tissues. The analyses targeted a candidate set of 114 peptides previously identified in shotgun proteomic analyses, of which 104 were detectable in FFPE and frozen tissue. Although signal intensities for MRM of peptides from FFPE tissue were on average 66% of those in frozen tissue, median coefficients of variation (CV) for measurements in FFPE and frozen tissues were nearly identical (18-20%). Measurements of lysine C-terminal peptides and arginine C-terminal peptides from FFPE tissue were similarly reproducible (19.5% and 18.3% median CV, respectively). We further evaluated the precision of MRM-based quantitation by analysis of peptides from the Her2 receptor in FFPE and frozen tissues from a Her2 overexpressing mouse xenograft model of breast cancer and in human FFPE breast cancer specimens. We obtained equivalent MRM measurements of HER2 receptor levels in FFPE and frozen mouse xenografts derived from HER2-overexpressing BT474 cells and HER2-negative Sum159 cells. MRM analyses of 5 HER2-positive and 5 HER-negative human FFPE breast tumors confirmed the results of immunohistochemical analyses, thus demonstrating the feasibility of HER2 protein quantification in FFPE tissue specimens. The data demonstrate that MRM analyses can be performed with equal precision on FFPE and frozen tissues and that lysine-containing peptides can be selected for quantitative comparisons, despite the greater impact of formalin fixation on lysine residues. The data further illustrate the feasibility of applying MRM to quantify clinically important tissue biomarkers in FFPE specimens.

  14. Optimal de novo design of MRM experiments for rapid assay development in targeted proteomics.

    Bertsch, Andreas; Jung, Stephan; Zerck, Alexandra; Pfeifer, Nico; Nahnsen, Sven; Henneges, Carsten; Nordheim, Alfred; Kohlbacher, Oliver


    Targeted proteomic approaches such as multiple reaction monitoring (MRM) overcome problems associated with classical shotgun mass spectrometry experiments. Developing MRM quantitation assays can be time consuming, because relevant peptide representatives of the proteins must be found and their retention time and the product ions must be determined. Given the transitions, hundreds to thousands of them can be scheduled into one experiment run. However, it is difficult to select which of the transitions should be included into a measurement. We present a novel algorithm that allows the construction of MRM assays from the sequence of the targeted proteins alone. This enables the rapid development of targeted MRM experiments without large libraries of transitions or peptide spectra. The approach relies on combinatorial optimization in combination with machine learning techniques to predict proteotypicity, retention time, and fragmentation of peptides. The resulting potential transitions are scheduled optimally by solving an integer linear program. We demonstrate that fully automated construction of MRM experiments from protein sequences alone is possible and over 80% coverage of the targeted proteins can be achieved without further optimization of the assay.

  15. Method and platform standardization in MRM-based quantitative plasma proteomics.

    Percy, Andrew J; Chambers, Andrew G; Yang, Juncong; Jackson, Angela M; Domanski, Dominik; Burkhart, Julia; Sickmann, Albert; Borchers, Christoph H


    There exists a growing demand in the proteomics community to standardize experimental methods and liquid chromatography-mass spectrometry (LC/MS) platforms in order to enable the acquisition of more precise and accurate quantitative data. This necessity is heightened by the evolving trend of verifying and validating candidate disease biomarkers in complex biofluids, such as blood plasma, through targeted multiple reaction monitoring (MRM)-based approaches with stable isotope-labeled standards (SIS). Considering the lack of performance standards for quantitative plasma proteomics, we previously developed two reference kits to evaluate the MRM with SIS peptide approach using undepleted and non-enriched human plasma. The first kit tests the effectiveness of the LC/MRM-MS platform (kit #1), while the second evaluates the performance of an entire analytical workflow (kit #2). Here, these kits have been refined for practical use and then evaluated through intra- and inter-laboratory testing on 6 common LC/MS platforms. For an identical panel of 22 plasma proteins, similar concentrations were determined, regardless of the kit, instrument platform, and laboratory of analysis. These results demonstrate the value of the kit and reinforce the utility of standardized methods and protocols. The proteomics community needs standardized experimental protocols and quality control methods in order to improve the reproducibility of MS-based quantitative data. This need is heightened by the evolving trend for MRM-based validation of proposed disease biomarkers in complex biofluids such as blood plasma. We have developed two kits to assist in the inter- and intra-laboratory quality control of MRM experiments: the first kit tests the effectiveness of the LC/MRM-MS platform (kit #1), while the second evaluates the performance of an entire analytical workflow (kit #2). In this paper, we report the use of these kits in intra- and inter-laboratory testing on 6 common LC/MS platforms. This

  16. New High-Performance Liquid Chromatography Coupled Mass Spectrometry Method for the Detection of Lobster and Shrimp Allergens in Food Samples via Multiple Reaction Monitoring and Multiple Reaction Monitoring Cubed.

    Korte, Robin; Monneuse, Jean-Marc; Gemrot, Elodie; Metton, Isabelle; Humpf, Hans-Ulrich; Brockmeyer, Jens


    Crustacean shellfish allergy ranks among the most frequent and severe food allergies for adults, demanding rugged and sensitive analytical routine methods. The objective of this study was therefore to develop a mass spectrometric approach for the detection of contamination with shrimp and lobster, two economically important types of crustaceans, in complex food matrices. Following a biomarker approach, we identified proteotypic peptides and developed a multiple reaction monitoring (MRM) method allowing for the identification and differentiation of shrimp and lobster in the food matrix at concentrations down to 0.1%. To further enhance sensitivity, we employed the MRM-cubed (MRM(3)) mode, which allowed us to detect crustaceans down to concentrations of 25 μg/g (crustacean/food, 0.0025%). We hereby present the first mass spectrometric method for the detection of shrimp and lobster in food matrices.

  17. A Database of Reaction Monitoring Mass Spectrometry Assays for Elucidating Therapeutic Response in Cancer

    Remily-Wood, Elizabeth R.; Liu, Richard Z.; Xiang, Yun; Chen, Yi; Thomas, C. Eric; Rajyaguru, Neal; Kaufman, Laura M.; Ochoa, Joana E.; Hazlehurst, Lori; Pinilla-Ibarz, Javier; Lancet, Jeffrey; Zhang, Guolin; Haura, Eric; Shibata, David; Yeatman, Timothy; Smalley, Keiran S.M.; Dalton, William S.; Huang, Emina; Scott, Ed; Bloom, Gregory C.; Eschrich, Steven A.; Koomen, John M.


    Purpose The Quantitative Assay Database (QuAD),, facilitates widespread implementation of quantitative mass spectrometry in cancer biology and clinical research through sharing of methods and reagents for monitoring protein expression and modification. Experimental Design Liquid chromatography coupled to multiple reaction monitoring mass spectrometry (LC-MRM) assays are developed using SDS-PAGE fractionated lysates from cancer cell lines. Pathway maps created using GeneGO Metacore provide the biological relationships between proteins and illustrate concepts for multiplexed analysis; each protein can be selected to examine assay development at the protein and peptide level. Results The coupling of SDS-PAGE and LC-MRM screening has been used to detect 876 peptides from 218 cancer-related proteins in model systems including colon, lung, melanoma, leukemias, and myeloma, which has led to the development of 95 quantitative assays including stable-isotope labeled peptide standards. Methods are published online and peptide standards are made available to the research community. Protein expression measurements for heat shock proteins, including a comparison with ELISA and monitoring response to the HSP90 inhibitor, 17-DMAG, are used to illustrate the components of the QuAD and its potential utility. Conclusions and Clinical Relevance This resource enables quantitative assessment of protein components of signaling pathways and biological processes and holds promise for systematic investigation of treatment responses in cancer. PMID:21656910

  18. P202-S Expanding the Capabilities of Peptide MRM-Based Assays in Plasma Using a Hybrid Triple-Quadrupole Linear Ion-Trap Mass Spectrometer

    Hunter, C.


    As the study of protein biomarkers increases in importance, technical limitations to the detection of low-abundance proteins and high-throughput, high-precision quantitation remain to be overcome. The complexity and dynamic range of the plasma proteome makes the task of specific, quantitative detection even more challenging. Multiple reaction monitoring (MRM) capabilities of triple quadrupole MS systems have been explored as solutions to this challenge due to their well-known sensitivity and ...

  19. A Generic Multiple Reaction Monitoring Based Approach for Plant Flavonoids Profiling Using a Triple Quadrupole Linear Ion Trap Mass Spectrometry

    Yan, Zhixiang; Lin, Ge; Ye, Yang; Wang, Yitao; Yan, Ru


    Flavonoids are one of the largest classes of plant secondary metabolites serving a variety of functions in plants and associating with a number of health benefits for humans. Typically, they are co-identified with many other secondary metabolites using untargeted metabolomics. The limited data quality of untargeted workflow calls for a shift from the breadth-first to the depth-first screening strategy when a specific biosynthetic pathway is focused on. Here we introduce a generic multiple reaction monitoring (MRM)-based approach for flavonoids profiling in plants using a hybrid triple quadrupole linear ion trap (QTrap) mass spectrometer. The approach includes four steps: (1) preliminary profiling of major aglycones by multiple ion monitoring triggered enhanced product ion scan (MIM-EPI); (2) glycones profiling by precursor ion triggered EPI scan (PI-EPI) of major aglycones; (3) comprehensive aglycones profiling by combining MIM-EPI and neutral loss triggered EPI scan (NL-EPI) of major glycone; (4) in-depth flavonoids profiling by MRM-EPI with elaborated MRM transitions. Particularly, incorporation of the NH3 loss and sugar elimination proved to be very informative and confirmative for flavonoids screening. This approach was applied for profiling flavonoids in Astragali radix ( Huangqi), a famous herb widely used for medicinal and nutritional purposes in China. In total, 421 flavonoids were tentatively characterized, among which less than 40 have been previously reported in this medicinal plant. This MRM-based approach provides versatility and sensitivity that required for flavonoids profiling in plants and serves as a useful tool for plant metabolomics.

  20. Application of LC-MS/MS MRM to Determine Staphylococcal Enterotoxins (SEB and SEA) in Milk.

    Andjelkovic, Mirjana; Tsilia, Varvara; Rajkovic, Andreja; De Cremer, Koen; Van Loco, Joris


    Staphylococcus aureus is one of the important aetiological agents of food intoxications in Europe and can cause gastro-enteritis through the production of various staphylococcal enterotoxins (SEs) in foods. Due to their stability and ease of production and dissemination, some SEs have also been studied as potential agents for bioterrorism. Therefore, specific and accurate analytical tools are required to detect and quantify SEs. Online solid-phase extraction liquid chromatography electrospray ionization tandem mass spectrometry (online SPE-LC-ESI-MS/MS) based on multiple reaction monitoring (MRM) was used to detect and quantify two types of SE (A and B) spiked in milk and buffer solution. SE extraction and concentration was performed according to the European Screening Method developed by the European Reference Laboratory for Coagulase Positive Staphylococci. Trypsin digests were screened for the presence of SEs using selected proteotypic heavy-labeled peptides as internal standards. SEA and SEB were successfully detected in milk samples using LC-MS/MS in MRM mode. The selected SE peptides were proteotypic for each toxin, allowing the discrimination of SEA and SEB in a single run. The detection limit of SEA and SEB was approximately 8 and 4 ng/g, respectively.

  1. Development of a dynamic multiple reaction monitoring method for determination of digoxin and six active components of Ginkgo biloba leaf extract in rat plasma.

    Rao, Zhi; Qin, Hongyan; Wei, Yuhui; Zhou, Yan; Zhang, Guoqiang; Zhang, Fan; Shao, Yunyun; Huang, Jing; Wu, Xin'an


    A new liquid chromatography-tandem mass spectrometry (LC-MS/MS) method by using dynamic multiple reaction monitoring (DMRM) has been developed and validated for the simultaneous determination of digoxin (DGX) and six main components of Ginkgo biloba leaf extract (GBE) in rat plasma. Comparing with the conventional multiple reaction monitoring (MRM), DMRM dramatically decreases the number of concurrent MRM transitions, and significantly extended the dwell time, which provided much higher sensitivity and reproducibility than MRM when complex multi-component samples were quantified. The plasma samples were protein precipitated with methanol, the detection was accomplished with electro-spray ionization (ESI) as the ion source operating in the negative ionization mode, with methanol and water as mobile phase, and with an Agilent Zorbax eclipse plus C18 column (4.6 × 100 mm, 3.5 μm) as the analytical column. The total run time was 12.0 min. The validation of the method was implemented including specificity, linearity, accuracy, precision, recovery, matrix effect and stability. This method was successfully applied to the herb-drug pharmacokinetic interaction study of DGX combined with GBE after oral administration to rats. The result indicated that co-administration of GBE and DGX significantly influenced the pharmacokinetics of DGX when compared to that of single DGX-treated rats.

  2. Selective and sensitive quantification of the cytochrome P450 3A4 protein in human liver homogenates through multiple reaction monitoring mass spectrometry.

    Cieślak, Anna; Kelly, Isabelle; Trottier, Jocelyn; Verreault, Mélanie; Wunsch, Ewa; Milkiewicz, Piotr; Poirier, Guy; Droit, Arnaud; Barbier, Olivier


    This study aimed at establishing a sensitive multiple reaction monitoring-mass spectrometry (MRM-MS) method for the quantification of the drug metabolizing cytochrome P450 (CYP)3A4 enzyme in human liver homogenates. Liver samples were subjected to trypsin digestion. MRM-MS analyses were performed using three transitions optimized on one purified synthetic peptide unique to CYP3A4 and the standardizing protein, calnexin. Coefficient of variations for the precision and reproducibility of the MRM-MS measurement were also determined. The method was applied to liver samples from ten non-cholestatic donors and 34 cholestatic patients with primary biliary cholangitis (n = 12; PBC), primary sclerosing cholangitis (n = 10; PSC) or alcoholic liver disease (n = 12; ALD). The established method presented high sensitivity with limit of detection lower than 5 fmol, and was successfully applied for the absolute and relative quantification of CYP3A4 in both whole liver homogenate and microsomal fractions. When all groups were analyzed together, a significant correlation was observed for the MRM-based CYP3A4 protein quantification in homogenates and microsomes (r = 0.49, p < 0.001). No statistically significant difference was detected between CYP3A4 levels in PSC, PBC, ALD and control samples. Finally, the MRM-MS quantification of CYP3A4 in homogenates also correlated (r = 0.44; p < 0.05) with the level of enzyme activity in the same samples, as determined by measuring the chenodeoxycholic to hyocholic acid conversion. The established method provides a sensitive tool to evaluate the CYP3A4 protein in human liver homogenates from patients with normal or chronic/severe hepatic injury.

  3. Diagnosis of Morquio Syndrome in Dried Blood Spots Based on a New MRM-MS Assay.

    Claudia Cozma

    Full Text Available Mucopolysaccharidosis IVA (MPS IVA; Morquio A disease is an autosomal recessive disease caused and characterized by a decreased activity of N-acetylgalactosamine-6-sulfate sulfatase (GALNS, resulting in accumulation of keratan sulfate and chondroitin-6-sulfate in tissues and secondary organ damage. Recently approved enzyme replacement therapy renders the easy and early identification of MPS IVA of out-most importance.We propose a completely new assay for the stable and reproducible detection of GALNS deficiency in dry blood spots (DBS. For the validation blood samples were taken from 59 healthy individuals and 24 randomly selected genetically confirmed MPS IVA patients. The material extracted from DBS was incubated with a 4-methylumbelliferyl-β-D-galactopyranoside-6-sulfate as a specific substrate. Final enzymatic product, 4-methylumbelliferone, obtained after adding exogenous beta-galactosidase, was quantified by LC/MRM-MS (liquid-chromatography/multiple-reaction-monitoring mass-spectrometry. 4-propyl-5-hydroxy-7-methyl-2h-chromen-2-one was used as internal standard, a compound with a similar molecular structure and fragmentation pattern in negative ion mode as 4-methylumbelliferone.The enzymatic assay yielded a positive and negative predictive value of 1.0 for genetically confirmed MPS IVA patients (GALNS activity of 0.35 ± 0.21 μmol/L/h and for controls with normal GALNS activity (23.1 ± 5.3 μmol/L /h. With present enzymatic conditions, the reaction yield in dried blood spots is at least 20 fold higher than any previously reported data with other assays.The present LC/MRM-MS based assay for MPS IVA diagnosis provides an easy, highly-standardized, accurate and innovative quantification of the enzymatic product in vitro and distinguishes perfectly between MPS IVA affected patients and normal controls. This technique will significantly simplify the early detection of MPS IVA patients.

  4. NMR reaction monitoring in flow synthesis

    M. Victoria Gomez


    Full Text Available Recent advances in the use of flow chemistry with in-line and on-line analysis by NMR are presented. The use of macro- and microreactors, coupled with standard and custom made NMR probes involving microcoils, incorporated into high resolution and benchtop NMR instruments is reviewed. Some recent selected applications have been collected, including synthetic applications, the determination of the kinetic and thermodynamic parameters and reaction optimization, even in single experiments and on the μL scale. Finally, software that allows automatic reaction monitoring and optimization is discussed.

  5. Quantitative analysis of low-abundance serological proteins with peptide affinity-based enrichment and pseudo-multiple reaction monitoring by hybrid quadrupole time-of-flight mass spectrometry.

    Kim, Kwang Hoe; Ahn, Yeong Hee; Ji, Eun Sun; Lee, Ju Yeon; Kim, Jin Young; An, Hyun Joo; Yoo, Jong Shin


    Multiple reaction monitoring (MRM) is commonly used for the quantitative analysis of proteins during mass pectrometry (MS), and has excellent specificity and sensitivity for an analyte in a complex sample. In this study, a pseudo-MRM method for the quantitative analysis of low-abundance serological proteins was developed using hybrid quadrupole time-of-flight (hybrid Q-TOF) MS and peptide affinity-based enrichment. First, a pseudo-MRM-based analysis using hybrid Q-TOF MS was performed for synthetic peptides selected as targets and spiked into tryptic digests of human serum. By integrating multiple transition signals corresponding to fragment ions in the full scan MS/MS spectrum of a precursor ion of the target peptide, a pseudo-MRM MS analysis of the target peptide showed an increased signal-to-noise (S/N) ratio and sensitivity, as well as an improved reproducibility. The pseudo-MRM method was then used for the quantitative analysis of the tryptic peptides of two low-abundance serological proteins, tissue inhibitor of metalloproteinase 1 (TIMP1) and tissue-type protein tyrosine phosphatase kappa (PTPκ), which were prepared with peptide affinity-based enrichment from human serum. Finally, this method was used to detect femtomolar amounts of target peptides derived from TIMP1 and PTPκ, with good coefficients of variation (CV 2.7% and 9.8%, respectively), using a few microliters of human serum from colorectal cancer patients. The results suggest that pseudo-MRM using hybrid Q-TOF MS, combined with peptide affinity-based enrichment, could become a promising alternative for the quantitative analysis of low-abundance target proteins of interest in complex serum samples that avoids protein depletion.

  6. Multiple-reaction monitoring for multiplex detection of three bacterial toxins using liquid chromatography-tandem mass spectrometry.

    Alam, S I; Uppal, A; Gupta, P; Kamboj, D V


    Clostridium perfringens epsilon toxin, staphylococcal enterotoxin B and shiga toxin are implicated in a number of diseases and food-borne intoxications and are considered potential agents for bioterrorism and warfare. Artificially generated aerosol is the likely mode of delivery of these for nefarious uses, potentially capable of causing mass destruction to human and animal health by inhalation of toxic bioaerosol. Multiplex and unambiguous detection of these agents is of paramount importance for emergency response in a biothreat scenario and for food safety. Multiple-reaction monitoring (MRM) assay for simultaneous monitoring of the three toxins is reported here using reverse-phase high-performance liquid chromatography-electrospray ionization-tandem mass spectrometry. Three different peptides with two fragment ions each were considered for quantification and confirmation. One of the three MRM transitions from each toxin, which exhibited the best sensitivity, was selected for multiplexing of the assay. Simulating a biothreat scenario wherein the bioaerosol is collected in 10 ml of buffer, the multiplex assay was tested with blind samples with one or more of the three toxins even in the presence of interfering Escherichia coli lysate proteins. © 2016 The Society for Applied Microbiology.

  7. Multiple reaction monitoring and multiple reaction monitoring cubed based assays for the quantitation of apolipoprotein F.

    Kumar, Abhinav; Gangadharan, Bevin; Zitzmann, Nicole


    Apolipoprotein F (APO-F) is a novel low abundance liver fibrosis biomarker and its concentration decreases in human serum and plasma across liver fibrosis stages. Current antibody based assays for APO-F suffer from limitations such as unspecific binding, antibody availability and undetectable target if the protein is degraded; and so an antibody-free assay has the potential to be a valuable diagnostic tool. We report an antibody-free, rapid, sensitive, selective and robust LC-MS/MS (MRM and MRM(3)) method for the detection and quantitation of APO-F in healthy human plasma. With further analysis of clinical samples, this LC-MS based method could be established as the first ever antibody-free biomarker assay for liver fibrosis. We explain the use of Skyline software for peptide selection and the creation of a reference library to aid in true peak identification of endogenous APO-F peptides in digests of human plasma without protein or peptide enrichment. Detection of a glycopeptide using MRM-EPI mode and reduction of interferences using MRM3 are explained. The amount of APO-F in human plasma from a healthy volunteer was determined to be 445.2ng/mL, the coefficient of variation (CV) of precision for 20 injections was <12% and the percentage error of each point along the calibration curve was calculated to be <8%, which is in line with the assay requirements for clinical samples.

  8. PChopper: high throughput peptide prediction for MRM/SRM transition design

    Huang Jeffrey T-J


    Full Text Available Abstract Background The use of selective reaction monitoring (SRM based LC-MS/MS analysis for the quantification of phosphorylation stoichiometry has been rapidly increasing. At the same time, the number of sites that can be monitored in a single LC-MS/MS experiment is also increasing. The manual processes associated with running these experiments have highlighted the need for computational assistance to quickly design MRM/SRM candidates. Results PChopper has been developed to predict peptides that can be produced via enzymatic protein digest; this includes single enzyme digests, and combinations of enzymes. It also allows digests to be simulated in 'batch' mode and can combine information from these simulated digests to suggest the most appropriate enzyme(s to use. PChopper also allows users to define the characteristic of their target peptides, and can automatically identify phosphorylation sites that may be of interest. Two application end points are available for interacting with the system; the first is a web based graphical tool, and the second is an API endpoint based on HTTP REST. Conclusions Service oriented architecture was used to rapidly develop a system that can consume and expose several services. A graphical tool was built to provide an easy to follow workflow that allows scientists to quickly and easily identify the enzymes required to produce multiple peptides in parallel via enzymatic digests in a high throughput manner.

  9. Monitoring enzymatic reactions with in situ sensors

    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.


    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.

  10. An MRM-based workflow for absolute quantitation of lysine-acetylated metabolic enzymes in mouse liver.

    Xu, Leilei; Wang, Fang; Xu, Ying; Wang, Yi; Zhang, Cuiping; Qin, Xue; Yu, Hongxiu; Yang, Pengyuan


    As a key post-translational modification mechanism, protein acetylation plays critical roles in regulating and/or coordinating cell metabolism. Acetylation is a prevalent modification process in enzymes. Protein acetylation modification occurs in sub-stoichiometric amounts; therefore extracting biologically meaningful information from these acetylation sites requires an adaptable, sensitive, specific, and robust method for their quantification. In this work, we combine immunoassays and multiple reaction monitoring-mass spectrometry (MRM-MS) technology to develop an absolute quantification for acetylation modification. With this hybrid method, we quantified the acetylation level of metabolic enzymes, which could demonstrate the regulatory mechanisms of the studied enzymes. The development of this quantitative workflow is a pivotal step for advancing our knowledge and understanding of the regulatory effects of protein acetylation in physiology and pathophysiology.

  11. Analysis of polymer molecules including reaction monitoring and control

    Schoenmakers, P.; van Herk, A.M.


    To monitor, control, and optimize emulsion polymerisations, there is a need to perform a variety of different measurements. The monomer conversion is a key parameter to monitor and control the reaction. A rapid response is required for real-time reaction monitoring. This chapter considers on-line an

  12. Multiple Reaction Monitoring for Direct Quantitation of Intact Proteins Using a Triple Quadrupole Mass Spectrometer.

    Wang, Evelyn H; Combe, Peter C; Schug, Kevin A


    Methods that can efficiently and effectively quantify proteins are needed to support increasing demand in many bioanalytical fields. Triple quadrupole mass spectrometry (QQQ-MS) is sensitive and specific, and it is routinely used to quantify small molecules. However, low resolution fragmentation-dependent MS detection can pose inherent difficulties for intact proteins. In this research, we investigated variables that affect protein and fragment ion signals to enable protein quantitation using QQQ-MS. Collision induced dissociation gas pressure and collision energy were found to be the most crucial variables for optimization. Multiple reaction monitoring (MRM) transitions for seven standard proteins, including lysozyme, ubiquitin, cytochrome c from both equine and bovine, lactalbumin, myoglobin, and prostate-specific antigen (PSA) were determined. Assuming the eventual goal of applying such methodology is to analyze protein in biological fluids, a liquid chromatography method was developed. Calibration curves of six standard proteins (excluding PSA) were obtained to show the feasibility of intact protein quantification using QQQ-MS. Linearity (2-3 orders), limits of detection (0.5-50 μg/mL), accuracy (protein. Sensitivities for different proteins varied considerably. Biological fluids, including human urine, equine plasma, and bovine plasma were used to demonstrate the specificity of the approach. The purpose of this model study was to identify, study, and demonstrate the advantages and challenges for QQQ-MS-based intact protein quantitation, a largely underutilized approach to date.

  13. Multiple Reaction Monitoring for Direct Quantitation of Intact Proteins Using a Triple Quadrupole Mass Spectrometer

    Wang, Evelyn H.; Combe, Peter C.; Schug, Kevin A.


    Methods that can efficiently and effectively quantify proteins are needed to support increasing demand in many bioanalytical fields. Triple quadrupole mass spectrometry (QQQ-MS) is sensitive and specific, and it is routinely used to quantify small molecules. However, low resolution fragmentation-dependent MS detection can pose inherent difficulties for intact proteins. In this research, we investigated variables that affect protein and fragment ion signals to enable protein quantitation using QQQ-MS. Collision induced dissociation gas pressure and collision energy were found to be the most crucial variables for optimization. Multiple reaction monitoring (MRM) transitions for seven standard proteins, including lysozyme, ubiquitin, cytochrome c from both equine and bovine, lactalbumin, myoglobin, and prostate-specific antigen (PSA) were determined. Assuming the eventual goal of applying such methodology is to analyze protein in biological fluids, a liquid chromatography method was developed. Calibration curves of six standard proteins (excluding PSA) were obtained to show the feasibility of intact protein quantification using QQQ-MS. Linearity (2-3 orders), limits of detection (0.5-50 μg/mL), accuracy (protein. Sensitivities for different proteins varied considerably. Biological fluids, including human urine, equine plasma, and bovine plasma were used to demonstrate the specificity of the approach. The purpose of this model study was to identify, study, and demonstrate the advantages and challenges for QQQ-MS-based intact protein quantitation, a largely underutilized approach to date.

  14. Evaluation of interspecimen trypsin digestion efficiency prior to multiple reaction monitoring-based absolute protein quantification with native protein calibrators.

    van den Broek, Irene; Smit, Nico P M; Romijn, Fred P H T M; van der Laarse, Arnoud; Deelder, André M; van der Burgt, Yuri E M; Cobbaert, Christa M


    Implementation of quantitative clinical chemistry proteomics (qCCP) requires targeted proteomics approaches, usually involving bottom-up multiple reaction monitoring-mass spectrometry (MRM-MS) with stable-isotope labeled standard (SIS) peptides, to move toward more accurate measurements. Two aspects of qCCP that deserve special attention are (1) proper calibration and (2) the assurance of consistent digestion. Here, we describe the evaluation of tryptic digestion efficiency by monitoring various signature peptides, missed cleavages, and modifications during proteolysis of apolipoprotein A-I and B in normo- and hypertriglyceridemic specimens. Absolute quantification of apolipoprotein A-I and B was performed by LC-MRM-MS with SIS peptide internal standards at two time points (4 and 20 h), using three native protein calibrators. Comparison with an immunoturbidimetric assay revealed recoveries of 99.4 ± 6.5% for apolipoprotein A-I and 102.6 ± 7.2% for apolipoprotein B after 4 h of trypsin digestion. Protein recoveries after 20 h trypsin incubation equaled 95.9 ± 6.9% and 106.0 ± 10.0% for apolipoproteins A-I and B, respectively. In conclusion, the use of metrologically traceable, native protein calibrators looks promising for accurate quantification of apolipoprotein A-I and B. Selection of rapidly formed peptides, that is, with no or minor missed cleavages, and the use of short trypsin incubation times for these efficiently cleaved peptides are likely to further reduce the variability introduced by trypsin digestion and to improve the traceability of test results to reach the desirable analytical performance for clinical chemistry application.

  15. Acyl chains of phospholipase D transphosphatidylation products in Arabidopsis cells: a study using multiple reaction monitoring mass spectrometry.

    Dominique Rainteau

    Full Text Available BACKGROUND: Phospholipases D (PLD are major components of signalling pathways in plant responses to some stresses and hormones. The product of PLD activity is phosphatidic acid (PA. PAs with different acyl chains do not have the same protein targets, so to understand the signalling role of PLD it is essential to analyze the composition of its PA products in the presence and absence of an elicitor. METHODOLOGY/PRINCIPAL FINDINGS: Potential PLD substrates and products were studied in Arabidopsis thaliana suspension cells treated with or without the hormone salicylic acid (SA. As PA can be produced by enzymes other than PLD, we analyzed phosphatidylbutanol (PBut, which is specifically produced by PLD in the presence of n-butanol. The acyl chain compositions of PBut and the major glycerophospholipids were determined by multiple reaction monitoring (MRM mass spectrometry. PBut profiles of untreated cells or cells treated with SA show an over-representation of 160/18:2- and 16:0/18:3-species compared to those of phosphatidylcholine and phosphatidylethanolamine either from bulk lipid extracts or from purified membrane fractions. When microsomal PLDs were used in in vitro assays, the resulting PBut profile matched exactly that of the substrate provided. Therefore there is a mismatch between the acyl chain compositions of putative substrates and the in vivo products of PLDs that is unlikely to reflect any selectivity of PLDs for the acyl chains of substrates. CONCLUSIONS: MRM mass spectrometry is a reliable technique to analyze PLD products. Our results suggest that PLD action in response to SA is not due to the production of a stress-specific molecular species, but that the level of PLD products per se is important. The over-representation of 160/18:2- and 16:0/18:3-species in PLD products when compared to putative substrates might be related to a regulatory role of the heterogeneous distribution of glycerophospholipids in membrane sub-domains.

  16. MRM screening/biomarker discovery with linear ion trap MS: a library of human cancer-specific peptides

    Lazar Iulia M


    Full Text Available Abstract Background The discovery of novel protein biomarkers is essential in the clinical setting to enable early disease diagnosis and increase survivability rates. To facilitate differential expression analysis and biomarker discovery, a variety of tandem mass spectrometry (MS/MS-based protein profiling techniques have been developed. For achieving sensitive detection and accurate quantitation, targeted MS screening approaches, such as multiple reaction monitoring (MRM, have been implemented. Methods MCF-7 breast cancer protein cellular extracts were analyzed by 2D-strong cation exchange (SCX/reversed phase liquid chromatography (RPLC separations interfaced to linear ion trap MS detection. MS data were interpreted with the Sequest-based Bioworks software (Thermo Electron. In-house developed Perl-scripts were used to calculate the spectral counts and the representative fragment ions for each peptide. Results In this work, we report on the generation of a library of 9,677 peptides (p a, b, y ions in the spectrum, the retention time, and the top 10 most intense product ions that correspond to a given peptide. Only proteins identified by at least two spectral counts are listed. The experimental distribution of protein frequencies, as a function of molecular weight, closely matched the theoretical distribution of proteins in the human proteome, as provided in the SwissProt database. The amino acid sequence coverage of the identified proteins ranged from 0.04% to 98.3%. The highest-abundance proteins in the cellular extract had a molecular weight (MW Conclusion Preliminary experiments have demonstrated that putative biomarkers, that are not detectable by conventional data dependent MS acquisition methods in complex un-fractionated samples, can be reliable identified with the information provided in this library. Based on the spectral count, the quality of a tandem mass spectrum and the m/z values for a parent peptide and its most abundant daughter

  17. Stepped MS(All) Relied Transition (SMART): An approach to rapidly determine optimal multiple reaction monitoring mass spectrometry parameters for small molecules.

    Ye, Hui; Zhu, Lin; Wang, Lin; Liu, Huiying; Zhang, Jun; Wu, Mengqiu; Wang, Guangji; Hao, Haiping


    Multiple reaction monitoring (MRM) is a universal approach for quantitative analysis because of its high specificity and sensitivity. Nevertheless, optimization of MRM parameters remains as a time and labor-intensive task particularly in multiplexed quantitative analysis of small molecules in complex mixtures. In this study, we have developed an approach named Stepped MS(All) Relied Transition (SMART) to predict the optimal MRM parameters of small molecules. SMART requires firstly a rapid and high-throughput analysis of samples using a Stepped MS(All) technique (sMS(All)) on a Q-TOF, which consists of serial MS(All) events acquired from low CE to gradually stepped-up CE values in a cycle. The optimal CE values can then be determined by comparing the extracted ion chromatograms for the ion pairs of interest among serial scans. The SMART-predicted parameters were found to agree well with the parameters optimized on a triple quadrupole from the same vendor using a mixture of standards. The parameters optimized on a triple quadrupole from a different vendor was also employed for comparison, and found to be linearly correlated with the SMART-predicted parameters, suggesting the potential applications of the SMART approach among different instrumental platforms. This approach was further validated by applying to simultaneous quantification of 31 herbal components in the plasma of rats treated with a herbal prescription. Because the sMS(All) acquisition can be accomplished in a single run for multiple components independent of standards, the SMART approach are expected to find its wide application in the multiplexed quantitative analysis of complex mixtures.

  18. Quantification of emerging micropollutants in an amphipod crustacean by nanoliquid chromatography coupled to mass spectrometry using multiple reaction monitoring cubed mode.

    Sordet, Martin; Berlioz-Barbier, Alexandra; Buleté, Audrey; Garric, Jeanne; Vulliet, Emmanuelle


    An innovative analytical method has been developed to quantify the bioaccumulation in an amphipod crustacean (Gammarus fossarum) of three micropollutants regarded as anthropic-pollution markers: carbamazepine, oxazepam, and testosterone. A liquid-liquid extraction assisted by salts, known as QuEChERS (Quick, Easy, Cheap, Effective, Rugged, and Safe) was miniaturised and optimised, so it could be adapted to the low mass samples (approximatively 5mg dry weight). For this same reason and in order to obtain good sensitivity, ultra-trace analyses were carried out by means of nanoliquid chromatography. A preconcentration system by on-column trapping was optimised to increase the injection volume. In order to improve both sensitivity and selectivity, the multiple reaction monitoring cubed mode analyses (MRM(3)) were carried out, validated and compared to the classic MRM. To the best of our knowledge, this is the first time that MRM(3) is coupled to nanoliquid chromatography for the analysis and detection of organic micropollutants <300Da. The optimised extraction method exhibited recoveries superior to 80%. The limits of quantification of the target compounds were 0.3, 0.7 and 4.7ng/g (wet weight) for oxazepam, carbamazepine and testosterone, respectively and the limits of detection were 0.1, 0.3 and 2.2ng/g (wet weight), respectively. The intra- and inter-day precisions were inferior to 7.7% and 10.9%, respectively, for the three levels of concentration tested. The analytical strategy developed allowed to obtain limits of quantification lower than 1ng/g (wet weight) and to establish the kinetic bioconcentration of contaminants within G. fossarum. Copyright © 2016 Elsevier B.V. All rights reserved.

  19. Absolute Quantification of Prion Protein (90-231) Using Stable Isotope-Labeled Chymotryptic Peptide Standards in a LC-MRM AQUA Workflow

    Sturm, Robert; Sheynkman, Gloria; Booth, Clarissa; Smith, Lloyd M.; Pedersen, Joel A.; Li, Lingjun


    Substantial evidence indicates that the disease-associated conformer of the prion protein (PrPTSE) constitutes the etiologic agent in prion diseases. These diseases affect multiple mammalian species. PrPTSE has the ability to convert the conformation of the normal prion protein (PrPC) into a β-sheet rich form resistant to proteinase K digestion. Common immunological techniques lack the sensitivity to detect PrPTSE at subfemtomole levels, whereas animal bioassays, cell culture, and in vitro conversion assays offer higher sensitivity but lack the high-throughput the immunological assays offer. Mass spectrometry is an attractive alternative to the above assays as it offers high-throughput, direct measurement of a protein's signature peptide, often with subfemtomole sensitivities. Although a liquid chromatography-multiple reaction monitoring (LC-MRM) method has been reported for PrPTSE, the chemical composition and lack of amino acid sequence conservation of the signature peptide may compromise its accuracy and make it difficult to apply to multiple species. Here, we demonstrate that an alternative protease (chymotrypsin) can produce signature peptides suitable for a LC-MRM absolute quantification (AQUA) experiment. The new method offers several advantages, including: (1) a chymotryptic signature peptide lacking chemically active residues (Cys, Met) that can confound assay accuracy; (2) low attomole limits of detection and quantitation (LOD and LOQ); and (3) a signature peptide retaining the same amino acid sequence across most mammals naturally susceptible to prion infection as well as important laboratory models. To the authors' knowledge, this is the first report on the use of a non-tryptic peptide in a LC-MRM AQUA workflow.

  20. Flavanol Quantification of Grapes via Multiple Reaction Monitoring Mass Spectrometry. Application to Differentiation among Clones of Vitis vinifera L. cv. Rufete Grapes.

    García-Estévez, Ignacio; Alcalde-Eon, Cristina; Escribano-Bailón, M Teresa


    The determination of the detailed flavanol composition in food matrices is not a simple task because of the structural similarities of monomers and, consequently, oligomers and polymers. The aim of this study was the development and validation of an HPLC-MS/MS-multiple reaction monitoring (MRM) method that would allow the accurate and precise quantification of catechins, gallocatechins, and oligomeric proanthocyanidins. The high correlation coefficients of the calibration curves (>0.993), the recoveries not statistically different from 100%, the good intra- and interday precisions (Vitis vinifera L. cv. Rufete grapes. Seventy-two (38 nongalloylated and 34 galloylated) and 53 (24 procyanidins and 29 prodelphinidins) flavanols have been identified and quantified in grape seed and grape skin, respectively. The use of HCA and PCA on the detailed flavanol composition has allowed differentiation among Rufete clones.

  1. Quantitative Raman reaction monitoring using the solvent as internal standard.

    P.A. Aarnoutse; J.A. Westerhuis


    Despite its potential, the use of Raman spectroscopy for real-time quantitative reaction monitoring is still rather limited. The problems of fluorescence, laser instability, low intensities, and the inner filter effect often outscore the advantages as narrow bands, the use of glass fibers, and low s

  2. A Fast and Robust UHPLC-MRM-MS Method to Characterize and Quantify Grape Skin Tannins after Chemical Depolymerization

    Lucie Pinasseau


    Full Text Available A rapid, sensitive, and selective analysis method using ultra high performance liquid chromatography coupled with triple-quadrupole mass spectrometry (UHPLC-QqQ-MS has been developed for the characterization and quantification of grape skin flavan-3-ols after acid-catalysed depolymerization in the presence of phloroglucinol (phloroglucinolysis. The compound detection being based on specific MS transitions in Multiple Reaction Monitoring (MRM mode, this fast gradient robust method allows analysis of constitutive units of grape skin proanthocyanidins, including some present in trace amounts, in a single injection, with a throughput of 6 samples per hour. This method was applied to a set of 214 grape skin samples from 107 different red and white grape cultivars grown under two conditions in the vineyard, irrigated or non-irrigated. The results of triplicate analyses confirmed the robustness of the method, which was thus proven to be suitable for high-throughput and large-scale metabolomics studies. Moreover, these preliminary results suggest that analysis of tannin composition is relevant to investigate the genetic bases of grape response to drought.

  3. UPLC-MRM Mass Spectrometry Method for Measurement of the Coagulation Inhibitors Dabigatran and Rivaroxaban in Human Plasma and Its Comparison with Functional Assays.

    Joachim Kuhn

    Full Text Available The fast, precise, and accurate measurement of the new generation of oral anticoagulants such as dabigatran and rivaroxaban in patients' plasma my provide important information in different clinical circumstances such as in the case of suspicion of overdose, when patients switch from existing oral anticoagulant, in patients with hepatic or renal impairment, by concomitant use of interaction drugs, or to assess anticoagulant concentration in patients' blood before major surgery.Here, we describe a quick and precise method to measure the coagulation inhibitors dabigatran and rivaroxaban using ultra-performance liquid chromatography electrospray ionization-tandem mass spectrometry in multiple reactions monitoring (MRM mode (UPLC-MRM MS. Internal standards (ISs were added to the sample and after protein precipitation; the sample was separated on a reverse phase column. After ionization of the analytes the ions were detected using electrospray ionization-tandem mass spectrometry. Run time was 2.5 minutes per injection. Ion suppression was characterized by means of post-column infusion.The calibration curves of dabigatran and rivaroxaban were linear over the working range between 0.8 and 800 μg/L (r >0.99. Limits of detection (LOD in the plasma matrix were 0.21 μg/L for dabigatran and 0.34 μg/L for rivaroxaban, and lower limits of quantification (LLOQ in the plasma matrix were 0.46 μg/L for dabigatran and 0.54 μg/L for rivaroxaban. The intraassay coefficients of variation (CVs for dabigatran and rivaroxaban were < 4% and 6%; respectively, the interassay CVs were < 6% for dabigatran and < 9% for rivaroxaban. Inaccuracy was < 5% for both substances. The mean recovery was 104.5% (range 83.8-113.0% for dabigatran and 87.0% (range 73.6-105.4% for rivaroxaban. No significant ion suppressions were detected at the elution times of dabigatran or rivaroxaban. Both coagulation inhibitors were stable in citrate plasma at -20°C, 4°C and even at RT for at

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

    Feindel, Kirk W


    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.

  5. Spontaneous adverse drug reaction monitoring in oncology: Our experience

    K Kaur


    Full Text Available Background: Adverse drug reaction (ADR monitoring is slowly developing as an important aspect of healthcare. The aim of the study was to study the pattern of adverse drug reactions in the Oncology department of a tertiary care hospital. Materials And Methods: This was a prospective study conducted in the Oncology department of a tertiary care hospital in which ADRs were reported spontaneously. The ADRs were noted from 1st January, 2007 to 30th June, 2011. Following were noted: demographics, premedication (if any, diagnosis, chemotherapy (regimen, cycles, medication history, and alteration in the treatment or co morbidities, ADRs (severity and management. Adverse drug reactions were noted by patient interview, collaborating with information on file, recording changes in the prescribing chart and investigations, consulting the doctor on duty. Results: During this study period, there were total of 14,475 visits of patients from which 2500 ADRs were recorded. Maximum number of ADRs were noted with platinum compounds (25.52% followed by pyrimidine antagonists (19.88%. The most common malignancy reported in our hospital was Carcinoma breast (20% followed by leukemia (12% and Ca ovary (12%. Alopecia (27.76% was the most common ADR followed by anemia (7.48%, thrombocytopenia (6.96% and constipation (6.16%. Conclusion: Alopecia is the most common ADR and platinum compounds were responsible for the maximum number of ADRs. The most common carcinoma reported during this period was carcinoma breast.

  6. Comparison of targeted peptide quantification assays for reductive dehalogenases by selective reaction monitoring (SRM) and precursor reaction monitoring (PRM).

    Schiffmann, Christian; Hansen, Rasmus; Baumann, Sven; Kublik, Anja; Nielsen, Per Halkjær; Adrian, Lorenz; von Bergen, Martin; Jehmlich, Nico; Seifert, Jana


    Targeted absolute protein quantification yields valuable information about physiological adaptation of organisms and is thereby of high interest. Especially for this purpose, two proteomic mass spectrometry-based techniques namely selective reaction monitoring (SRM) and precursor reaction monitoring (PRM) are commonly applied. The objective of this study was to establish an optimal quantification assay for proteins with the focus on those involved in housekeeping functions and putative reductive dehalogenase proteins from the strictly anaerobic bacterium Dehalococcoides mccartyi strain CBDB1. This microbe is small and slow-growing; hence, it provides little biomass for comprehensive proteomic analysis. We therefore compared SRM and PRM techniques. Eleven peptides were successfully quantified by both methods. In addition, six peptides were solely quantified by SRM and four by PRM, respectively. Peptides were spiked into a background of Escherichia coli lysate and the majority of peptides were quantifiable down to 500 amol absolute on column by both methods. Peptide quantification in CBDB1 lysate resulted in the detection of 15 peptides using SRM and 14 peptides with the PRM assay. Resulting quantification of five dehalogenases revealed copy numbers of <10 to 115 protein molecules per cell indicating clear differences in abundance of RdhA proteins during growth on hexachlorobenzene. Our results indicated that both methods show comparable sensitivity and that the combination of the mass spectrometry assays resulted in higher peptide coverage and thus more reliable protein quantification.

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

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


    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.

  8. Benchtop monitoring of reaction progress via visual recognition with a handheld UV lamp: in situ monitoring of boronic acids in the Suzuki-Miyaura reaction.

    Barder, Timothy E; Buchwald, Stephen L


    [reaction: see text] Although boronic acids are widely used in metal-catalyzed reactions, it is difficult to assay their consumption. As such, we developed a reversible fluorescent sensor that is activated upon binding a boronic acid. The sensor can be used to monitor consumption of a boronic acid in Suzuki-Miyaura reactions. Importantly, only a standard handheld long-wave UV lamp (365 nm) is required and fluorescence is easily detectable with the naked eye without disturbing the reaction mixture.

  9. Development and validation of LC-MS/MS method with multiple reactions monitoring mode for quantification of vanillin and syringaldehyde in plum brandies

    Tešević Vele


    Full Text Available An ultra-performance liquid chromatography-triple quadrupole mass spectrometry (UPLC-QqQ-MS/MS method with multiple reactions monitoring mode (MRM has been developed and validated for quantification of vanillin and syringaldehyde in plum brandy. The method showed good linearity (0.05 to 10 mgL−1 and low limits of detection and quantification (LOD and LOQ were 11.6 µgL−1 and 38.2 µgL−1 for vanillin, and 12.7 µgL−1 and 42.0 µgL−1 for syringaldehyde, respectively. The overall intra-day and inter-day variations were less than 4.21%, and the overall recovery over 93.0%. The correlation coefficients (R2 of the calibration curves were higher than 0.9999. In order to evaluate if the method is suitable for use as a routine analytical tool, in 31 Serbian plum brandy samples vanillin and syringaldehide were determined. [Projekat Ministarstva nauke Republike Srbije, br. 172053

  10. Tools and Techniques for Evaluating the Effects of Maintenance Resource Management (MRM) in Air Safety

    Taylor, James C.


    This research project was designed as part of a larger effort to help Human Factors (HF) implementers, and others in the aviation maintenance community, understand, evaluate, and validate the impact of Maintenance Resource Management (MRM) training programs, and other MRM interventions; on participant attitudes, opinions, behaviors, and ultimately on enhanced safety performance. It includes research and development of evaluation methodology as well as examination of psychological constructs and correlates of maintainer performance. In particular, during 2001, three issues were addressed. First a prototype process for measuring performance was developed and used. Second an automated calculator was developed to aid the HF implementer user in analyzing and evaluating local survey data. These results include being automatically compared with the experience from all MRM programs studied since 1991. Third the core survey (the Maintenance Resource Management Technical Operations Questionnaire, or 'MRM/TOQ') was further developed and tested to include topics of added relevance to the industry.

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

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


    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

  12. Discovery of colorectal cancer biomarker candidates by membrane proteomic analysis and subsequent verification using selected reaction monitoring (SRM) and tissue microarray (TMA) analysis.

    Kume, Hideaki; Muraoka, Satoshi; Kuga, Takahisa; Adachi, Jun; Narumi, Ryohei; Watanabe, Shio; Kuwano, Masayoshi; Kodera, Yoshio; Matsushita, Kazuyuki; Fukuoka, Junya; Masuda, Takeshi; Ishihama, Yasushi; Matsubara, Hisahiro; Nomura, Fumio; Tomonaga, Takeshi


    Recent advances in quantitative proteomic technology have enabled the large-scale validation of biomarkers. We here performed a quantitative proteomic analysis of membrane fractions from colorectal cancer tissue to discover biomarker candidates, and then extensively validated the candidate proteins identified. A total of 5566 proteins were identified in six tissue samples, each of which was obtained from polyps and cancer with and without metastasis. GO cellular component analysis predicted that 3087 of these proteins were membrane proteins, whereas TMHMM algorithm predicted that 1567 proteins had a transmembrane domain. Differences were observed in the expression of 159 membrane proteins and 55 extracellular proteins between polyps and cancer without metastasis, while the expression of 32 membrane proteins and 17 extracellular proteins differed between cancer with and without metastasis. A total of 105 of these biomarker candidates were quantitated using selected (or multiple) reaction monitoring (SRM/MRM) with stable synthetic isotope-labeled peptides as an internal control. The results obtained revealed differences in the expression of 69 of these proteins, and this was subsequently verified in an independent set of patient samples (polyps (n = 10), cancer without metastasis (n = 10), cancer with metastasis (n = 10)). Significant differences were observed in the expression of 44 of these proteins, including ITGA5, GPRC5A, PDGFRB, and TFRC, which have already been shown to be overexpressed in colorectal cancer, as well as proteins with unknown function, such as C8orf55. The expression of C8orf55 was also shown to be high not only in colorectal cancer, but also in several cancer tissues using a multicancer tissue microarray, which included 1150 cores from 14 cancer tissues. This is the largest verification study of biomarker candidate membrane proteins to date; our methods for biomarker discovery and subsequent validation using SRM/MRM will contribute to the

  13. A simple LC/MRM-MS-based method to quantify free linker-payload in antibody-drug conjugate preparations.

    Zmolek, Wesley; Bañas, Stefanie; Barfield, Robyn M; Rabuka, David; Drake, Penelope M


    Antibody-drug conjugates represent a growing class of biologic drugs that use the targeted specificity of an antibody to direct the localization of a small molecule drug, often a cytotoxic payload. After conjugation, antibody-drug conjugate preparations typically retain a residual amount of free (unconjugated) linker-payload. Monitoring this free small molecule drug component is important due to the potential for free payload to mediate unintended (off-target) toxicity. We developed a simple RP-HPLC/MRM-MS-based assay that can be rapidly employed to quantify free linker-payload. The method uses low sample volumes and offers an LLOQ of 10nM with 370pg on column. This analytical approach was used to monitor free linker-payload removal during optimization of the tangential flow filtration manufacturing step.

  14. Real time monitoring of accelerated chemical reactions by ultrasonication-assisted spray ionization mass spectrometry.

    Lin, Shu-Hsuan; Lo, Ta-Ju; Kuo, Fang-Yin; Chen, Yu-Chie


    Ultrasonication has been used to accelerate chemical reactions. It would be ideal if ultrasonication-assisted chemical reactions could be monitored by suitable detection tools such as mass spectrometry in real time. It would be helpful to clarify reaction intermediates/products and to have a better understanding of reaction mechanism. In this work, we developed a system for ultrasonication-assisted spray ionization mass spectrometry (UASI-MS) with an ~1.7 MHz ultrasonic transducer to monitor chemical reactions in real time. We demonstrated that simply depositing a sample solution on the MHz-based ultrasonic transducer, which was placed in front of the orifice of a mass spectrometer, the analyte signals can be readily detected by the mass spectrometer. Singly and multiply charged ions from small and large molecules, respectively, can be observed in the UASI mass spectra. Furthermore, the ultrasonic transducer used in the UASI setup accelerates the chemical reactions while being monitored via UASI-MS. The feasibility of using this approach for real-time acceleration/monitoring of chemical reactions was demonstrated. The reactions of Girard T reagent and hydroxylamine with steroids were used as the model reactions. Upon the deposition of reactant solutions on the ultrasonic transducer, the intermediate/product ions are readily generated and instantaneously monitored using MS within 1 s. Additionally, we also showed the possibility of using this reactive UASI-MS approach to assist the confirmation of trace steroids from complex urine samples by monitoring the generation of the product ions.

  15. Quantitative changes in proteins responsible for flavonoid and anthocyanin biosynthesis in strawberry fruit at different ripening stages: A targeted quantitative proteomic investigation employing multiple reaction monitoring.

    Song, Jun; Du, Lina; Li, Li; Kalt, Wilhelmina; Palmer, Leslie Campbell; Fillmore, Sherry; Zhang, Ying; Zhang, ZhaoQi; Li, XiHong


    To better understand the regulation of flavonoid and anthocyanin biosynthesis, a targeted quantitative proteomic investigation employing LC-MS with multiple reaction monitoring was conducted on two strawberry cultivars at three ripening stages. This quantitative proteomic workflow was improved through an OFFGEL electrophoresis to fractionate peptides from total protein digests. A total of 154 peptide transitions from 47 peptides covering 21 proteins and isoforms related to anthocyanin biosynthesis were investigated. The normalized protein abundance, which was measured using isotopically-labeled standards, was significantly changed concurrently with increased anthocyanin content and advanced fruit maturity. The protein abundance of phenylalanine ammonia-lyase; anthocyanidin synthase, chalcone isomerase; flavanone 3-hydroxylase; dihydroflavonol 4-reductase, UDP-glucose:flavonoid-3-O-glucosyltransferase, cytochrome c and cytochrome C oxidase subunit 2, was all significantly increased in fruit of more advanced ripeness. An interaction between cultivar and maturity was also shown with respect to chalcone isomerase. The good correlation between protein abundance and anthocyanin content suggested that a metabolic control point may exist for anthocyanin biosynthesis. This research provides insights into the process of anthocyanin formation in strawberry fruit at the level of protein concentration and reveals possible candidates in the regulation of anthocyanin formation during fruit ripening. To gain insight into the molecular mechanisms contributing to flavonoids and anthocyanin biosynthesis and regulation of strawberry fruit during ripening is challenging due to limited molecular biology tools and established hypothesis. Our targeted proteomic approach employing LC-MS/MS analysis and MRM technique to quantify proteins in relation to flavonoids and anthocyanin biosynthesis and regulation in strawberry fruit during fruit ripening is novel. The identification of peptides

  16. Application of enhanced gas chromatography/triple quadrupole mass spectrometry for monitoring petroleum weathering and forensic source fingerprinting in samples impacted by the Deepwater Horizon oil spill.

    Adhikari, Puspa L; Wong, Roberto L; Overton, Edward B


    Accurate characterization of petroleum hydrocarbons in complex and weathered oil residues is analytically challenging. This is primarily due to chemical compositional complexity of both the oil residues and environmental matrices, and the lack of instrumental selectivity due to co-elution of interferences with the target analytes. To overcome these analytical selectivity issues, we used an enhanced resolution gas chromatography coupled with triple quadrupole mass spectrometry in Multiple Reaction Monitoring (MRM) mode (GC/MS/MS-MRM) to eliminate interferences within the ion chromatograms of target analytes found in environmental samples. This new GC/MS/MS-MRM method was developed and used for forensic fingerprinting of deep-water and marsh sediment samples containing oily residues from the Deepwater Horizon oil spill. The results showed that the GC/MS/MS-MRM method increases selectivity, eliminates interferences, and provides more accurate quantitation and characterization of trace levels of alkyl-PAHs and biomarker compounds, from weathered oil residues in complex sample matrices. The higher selectivity of the new method, even at low detection limits, provides greater insights on isomer and homolog compositional patterns and the extent of oil weathering under various environmental conditions. The method also provides flat chromatographic baselines for accurate and unambiguous calculation of petroleum forensic biomarker compound ratios. Thus, this GC/MS/MS-MRM method can be a reliable analytical strategy for more accurate and selective trace level analyses in petroleum forensic studies, and for tacking continuous weathering of oil residues. Copyright © 2017 Elsevier Ltd. All rights reserved.

  17. Nanoreactors for simultaneous remote thermal activation and optical monitoring of chemical reactions.

    Vázquez-Vázquez, Carmen; Vaz, Belén; Giannini, Vincenzo; Pérez-Lorenzo, Moisés; Alvarez-Puebla, Ramon A; Correa-Duarte, Miguel A


    We report herein the design of plasmonic hollow nanoreactors capable of concentrating light at the nanometer scale for the simultaneous performance and optical monitoring of thermally activated reactions. These reactors feature the encapsulation of plasmonic nanoparticles on the inner walls of a mesoporous silica capsule. A Diels-Alder cycloaddition reaction was carried out in the inner cavities of these nanoreactors to evidence their efficacy. Thus, it is demonstrated that reactions can be accomplished in a confined volume without alteration of the temperature of the bulk solvent while allowing real-time monitoring of the reaction progress.

  18. mRM - multiscale Routing Model for Land Surface and Hydrologic Models

    Cuntz, M.; Thober, S.; Mai, J.; Samaniego, L. E.; Gochis, D. J.; Kumar, R.


    Routing streamflow through a river network is a basic step within any distributed hydrologic model. It integrates the generated runoff and allows comparison with observed discharge at the outlet of a catchment. The Muskingum routing is a textbook river routing scheme that has been implemented in Earth System Models (e.g., WRF-HYDRO), stand-alone routing schemes (e.g., RAPID), and hydrologic models (e.g., the mesoscale Hydrologic Model). Most implementations suffer from a high computational demand because the spatial routing resolution is fixed to that of the elevation model irrespective of the hydrologic modeling resolution. This is because the model parameters are scale-dependent and cannot be used at other resolutions without re-estimation. Here, we present the multiscale Routing Model (mRM) that allows for a flexible choice of the routing resolution. mRM exploits the Multiscale Parameter Regionalization (MPR) included in the open-source mesoscale Hydrologic Model (mHM, that relates model parameters to physiographic properties and allows to estimate scale-independent model parameters. mRM is currently coupled to mHM and is presented here as stand-alone Free and Open Source Software (FOSS). The mRM source code is highly modular and provides a subroutine for internal re-use in any land surface scheme. mRM is coupled in this work to the state-of-the-art land surface model Noah-MP. Simulation results using mRM are compared with those available in WRF-HYDRO for the Red River during the period 1990-2000. mRM allows to increase the routing resolution from 100m to more than 10km without deteriorating the model performance. Therefore, it speeds up model calculation by reducing the contribution of routing to total runtime from over 80% to less than 5% in the case of WRF-HYDRO. mRM thus makes discharge data available to land surface modeling with only little extra calculations.

  19. Substrate-Coated Illumination Droplet Spray Ionization: Real-Time Monitoring of Photocatalytic Reactions

    Zhang, Hong; Li, Na; Zhao, Dandan; Jiang, Jie; You, Hong


    Real-time monitoring of photocatalytic reactions facilitates the elucidation of the mechanisms of the reactions. However, suitable tools for real-time monitoring are lacking. Herein, a novel method based on droplet spray ionization named substrate-coated illumination droplet spray ionization (SCI-DSI) for direct analysis of photocatalytic reaction solution is reported. SCI-DSI addresses many of the analytical limitations of electrospray ionization (ESI) for analysis of photocatalytic-reaction intermediates, and has potential for both in situ analysis and real-time monitoring of photocatalytic reactions. In SCI-DSI-mass spectrometry (MS), a photocatalytic reaction occurs by loading sample solutions onto the substrate-coated cover slip and by applying UV light above the modified slip; one corner of this slip adjacent to the inlet of a mass spectrometer is the high-electric-field location for launching a charged-droplet spray. After both testing and optimizing the performance of SCI-DSI, the value of this method for in situ analysis and real-time monitoring of photocatalytic reactions was demonstrated by the removal of cyclophosphamide (CP) in TiO2/UV. Reaction times ranged from seconds to minutes, and the proposed reaction intermediates were captured and identified by tandem mass spectrometry. Moreover, the free hydroxyl radical (·OH) was identified as the main radicals for CP removal. These results show that SCI-DSI is suitable for in situ analysis and real-time monitoring of CP removal under TiO2-based photocatalytic reactions. SCI-DSI is also a potential tool for in situ analysis and real-time assessment of the roles of radicals during CP removal under TiO2-based photocatalytic reactions. Graphical Abstract[Figure not available: see fulltext.

  20. Monitoring of enzymatic reactions using capillary electrophoresis with conductivity detection


    Capillary electrophoresis combined with contactless conductivity detection allows to separate and detect the ionic species, which are neither UV absorbing nor fluorescent. This thesis focuses on the applications of this method on enzymatic reactions in different analytical tasks. First, the non-ionic species ethanol, glucose, ethyl acetate and ethyl butyrate were made accessible for analysis by capillary electrophoresis via charged products or byproducts obtained in enzymati...

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

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


    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.…

  2. Quantitative in situ and real-time monitoring of mechanochemical reactions.

    Halasz, Ivan; Friščić, Tomislav; Kimber, Simon A J; Užarević, Krunoslav; Puškarić, Andreas; Mottillo, Cristina; Julien, Patrick; Strukil, Vjekoslav; Honkimäki, Veijo; Dinnebier, Robert E


    An experimental technique for in situ and real-time monitoring of mechanochemical reactions in a shaker ball mill was recently described, which utilises highly penetrating X-ray radiation available at the ID15B beamline of the European Synchrotron Radiation Facility. Herein, we describe the first attempts to perform such reaction monitoring in a quantitative fashion, by introducing an internal X-ray diffraction standard. The use of silicon as an internal standard resolved the issue with variations of the amount of the sample in the X-ray beam due to the non-uniform distribution of the sample in the reaction jar and allowed, via Rietveld analysis, the first quantitative estimate of the amorphous phase content in a mechanochemical reaction as it is being milled. We also highlight problems associated with the non-ideal mixing of the reaction mixture.

  3. Measurement of the activation cross section for the (p,xn) reactions in niobium with potential applications as monitor reactions

    Avila-Rodriguez, M.A. [Edmonton PET Centre, Cross Cancer Institute, Edmonton, AB, T6G 1Z2 (Canada)], E-mail:; Wilson, J.S. [Edmonton PET Centre, Cross Cancer Institute, Edmonton, AB, T6G 1Z2 (Canada); Schueller, M.J. [Brookhaven National Laboratory, Upton, NY 11973 (United States); McQuarrie, S.A. [Edmonton PET Centre, Cross Cancer Institute, Edmonton, AB, T6G 1Z2 (Canada)


    Excitation functions of the {sup 93}Nb(p,n){sup 93m}Mo, {sup 93}Nb(p,pn){sup 92m}Nb and {sup 93}Nb(p,{alpha}n){sup 89}Zr nuclear reactions were measured up to 17.4 MeV by the conventional activation method using the stacked-foil technique. Stacks were irradiated at different incident energies on the TR19/9 cyclotron at the Edmonton PET Centre. The potential of the measured excitation functions for use as monitor reactions was evaluated and tested by measuring activity ratios at a different facility. Single Nb foils were irradiated at incident energies in the range from 12 to 19 MeV on the TR19/9 cyclotron at Brookhaven National Laboratory. Results are compared with the published data and with theoretical values as determined by the nuclear reaction model code EMPIRE.

  4. Monitoring infection: from blood culture to polymerase chain reaction (PCR).

    Book, Malte; Lehmann, Lutz Eric; Zhang, XiangHong; Stüber, Frank


    In patients with sepsis, diagnosis of blood stream infection (BSI) is a key concern to the therapist. Direct verification of pathogens in the blood stream executed by blood cultures (BC) still is regarded as the gold standard up to date. The quickest possible initiation of an appropriate antimicrobial therapy is a cornerstone of an effective therapy. Moreover, in this view BC can also serve to identify antimicrobial agents to target the pathogen. However, when employing BC the time needed until microbiological results are available ranges from 24 up to 72 h. Moreover, infections caused by multiple pathogens often remain undetected and concurrent antibiotic therapy may lower the overall sensitivity. Alternative pathogen characterization can be performed by polymerase chain reaction (PCR) based amplification methods. Results using PCR can be obtained within 6-8 h. Therefore, the time delay until an appropriate therapy can be reduced enormously. Moreover, these methods have the potential to enhance the sensitivity in the diagnosis of blood stream infections. Therefore, PCR based methods might be a valuable adjunct to present procedures of diagnosing bacteraemia.

  5. Monitorizing nitinol alloy surface reactions for biofouling studies

    Dinu, C.Z. [Max Planck Institute of Molecular Cell Biology and Genetics, Photenhauerstrasse 108, Dresden (Germany); Dinca, V.C. [National Institute for Laser, Plasma and Radiation Physics, PO Box MG-16, RO 77125 Bucharest (Romania)]. E-mail:; Soare, S. [UNIBUC-MICROGEN, University of Bucharest, Centre for Research, Education and Consulting in Microbiology, Genetics and Biotechnology (MICROGEN), Splaiul Independentei, 91-95, RO 76201 Bucharest (Romania); Moldovan, A. [Max Planck Institute of Molecular Cell Biology and Genetics, Photenhauerstrasse 108, Dresden (Germany); Smarandache, D. [UNIBUC-MICROGEN, University of Bucharest, Centre for Research, Education and Consulting in Microbiology, Genetics and Biotechnology (MICROGEN), Splaiul Independentei, 91-95, RO 76201 Bucharest (Romania); Scarisoareanu, N. [National Institute for Laser, Plasma and Radiation Physics, PO Box MG-16, RO 77125 Bucharest (Romania); Barbalat, A. [National Institute for Laser, Plasma and Radiation Physics, PO Box MG-16, RO 77125 Bucharest (Romania); Birjega, R. [National Institute for Laser, Plasma and Radiation Physics, PO Box MG-16, RO 77125 Bucharest (Romania); Dinescu, M. [National Institute for Laser, Plasma and Radiation Physics, PO Box MG-16, RO 77125 Bucharest (Romania); DiStefano, V. Ferrari [University of Rome La Sapienza, Department of Electronics, Rome (Italy)


    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.

  6. Monitorizing nitinol alloy surface reactions for biofouling studies

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


    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.

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

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


    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.

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

    Meher, Anil Kumar; Chen, Yu-Chie


    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.

  9. Monitoring the reaction between AlCl3 and o-xylene by using terahertz spectroscopy

    Jin, Wu-Jun; Li, Tao; Zhao, Kun; Zhao, Hui


    Terahertz time-domain spectroscopy (THz-TDS) is used to study the interaction between AlCl3 and o-xylene in a temperature range from 300 K to 368 K. For comparison, the three isomers of o-, m-, and p-xylene are measured by using THz-TDS. The o-xylene carries out isomerization reaction in the presence of catalyst AlCl3. The absorption coefficient of the mixed reaction solution is extracted and analyzed in the frequency range from 0.2 THz to 1.4 THz. The temperature dependence of the absorption coefficient, which is influenced by both the dissolution of AlCl3 and the production of the two other isomer resultants, is obtained, and it can indicate the process of the isomerization reaction. The results suggest that THz spectroscopy can be used to monitor the isomerization reaction and other reactions in chemical synthesis, petrochemical and biomedical fields.

  10. Sensitivity and specificity of unenhanced MR mammography (DWI combined with T2-weighted TSE imaging, ueMRM) for the differentiation of mass lesions

    Baltzer, Pascal A.T.; Benndorf, Matthias; Dietzel, Matthias; Kaiser, Werner A. [Friedrich Schiller University Jena, Institute of Diagnostic and Interventional Radiology, Jena (Germany); Gajda, Mieczyslaw [Institute of Pathology, Friedrich Schiller University Jena, Jena (Germany); Camara, Oumar [Friedrich Schiller University Jena, Clinic of Gynecology, Jena (Germany)


    This study was performed to assess the sensitivity and specificity for malignant and benign mass lesions of a diagnostic approach combining DWI with T2-weighted images (unenhanced MR mammography, ueMRM) and compare the results with contrast-enhanced MR mammography (ceMRM). Consecutive patients undergoing histopathological verification of mass lesions after MR mammography without prior breast interventions (contrast-enhanced T1-weighted, T2-weighted and DWI sequences) were eligible for this retrospective investigation. Two blinded observers first rated ueMRM and then ceMRM according to the BIRADS scale. Lesion size, ADC values and T2-weighted TSE descriptors were assessed. This study examined 81 lesions (27 benign, 54 malignant). Sensitivity of ueMRM was 93% (observer 1) and 86% (observer 2), respectively. Sensitivity of ceMRM was 96.5% (observer 1) and 98.3% (observer 2). Specificity was 85.2% (ueMRM) and 92.6% (ceMRM) for both observers. The differences between both methods and observers were not significant (P {>=} 0.09). Lesion size measurements did not differ significantly among all sequences analyzed. Tumor visibility was worse using ueMRM for both benign (P < 0.001) and malignant lesions (P = 0.004). Sensitivity and specificity of ueMRM in mass lesions equal that of ceMRM. However, a reduced lesion visibility in ueMRM may lead to more false-negative findings. (orig.)

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

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


    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…

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

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


    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…


    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...

  14. A Doctrine-oriented MRM Method in HLA-based Simulation

    HUSiquan; FANZhihua


    MRM (Multi-resolution modeling) is becoming more important as large complex distributed simulations are carried out inside and out of military simulation community. Most current distributed simulations are implemented in the framework of HLA (High level architecture), which was originally defined by US DOD (Department of defense) and has been accepted by IEEE and OMG as an industrial simulation standard. This paper analyzes the requirements of MRM in HLA (High level architecture)-based simulations. Traditional most adopted practical method "aggregation/disaggregation" has temporal inconsistency problem because it discard the other level as it's at one level. The mainstream theoretic method "MRE (Multiple representation entity)" conquers this problem by propagating changes at one resolution to others, but it has weakness in mapping consistence. This paper suggested a doctrine-oriented MRM method. This novel method has good operational easiness and keeps the consistency problem simpler than MRE by enforcing unidirectional map between entities in different resolutions. A case study is also provided to illustrate its advantage to aggregation/disaggregation method.

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

    Frank F. Roberto


    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.

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

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


    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.

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

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


    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.

  18. Large-scale multiplex absolute protein quantification of drug-metabolizing enzymes and transporters in human intestine, liver, and kidney microsomes by SWATH-MS: Comparison with MRM/SRM and HR-MRM/PRM.

    Nakamura, Kenji; Hirayama-Kurogi, Mio; Ito, Shingo; Kuno, Takuya; Yoneyama, Toshihiro; Obuchi, Wataru; Terasaki, Tetsuya; Ohtsuki, Sumio


    The purpose of the present study was to examine simultaneously the absolute protein amounts of 152 membrane and membrane-associated proteins, including 30 metabolizing enzymes and 107 transporters, in pooled microsomal fractions of human liver, kidney, and intestine by means of SWATH-MS with stable isotope-labeled internal standard peptides, and to compare the results with those obtained by MRM/SRM and high resolution (HR)-MRM/PRM. The protein expression levels of 27 metabolizing enzymes, 54 transporters, and six other membrane proteins were quantitated by SWATH-MS; other targets were below the lower limits of quantitation. Most of the values determined by SWATH-MS differed by less than 50% from those obtained by MRM/SRM or HR-MRM/PRM. Various metabolizing enzymes were expressed in liver microsomes more abundantly than in other microsomes. Ten, 13, and eight transporters listed as important for drugs by International Transporter Consortium were quantified in liver, kidney, and intestinal microsomes, respectively. Our results indicate that SWATH-MS enables large-scale multiplex absolute protein quantification while retaining similar quantitative capability to MRM/SRM or HR-MRM/PRM. SWATH-MS is expected to be useful methodology in the context of drug development for elucidating the molecular mechanisms of drug absorption, metabolism, and excretion in the human body based on protein profile information.

  19. Evaluation of multiple reaction monitoring cubed for the analysis of tachykinin related peptides in rat spinal cord using a hybrid triple quadrupole-linear ion trap mass spectrometer.

    Pailleux, Floriane; Beaudry, Francis


    Targeted peptide methods generally use HPLC-MS/MRM approaches. Although dependent on the instrumental resolution, interferences may occur while performing analysis of complex biological matrices. HPLC-MS/MRM(3) is a technique, which provides a significantly better selectivity, compared with HPLC-MS/MRM assay. HPLC-MS/MRM(3) allows the detection and quantitation by enriching standard MRM with secondary product ions that are generated within the linear ion trap. Substance P (SP) and neurokinin A (NKA) are tachykinin peptides playing a central role in pain transmission. The objective of this study was to verify whether HPLC-MS/MRM(3) could provide significant advantages over a more traditional HPLC-MS/MRM assay for the quantification of SP and NKA in rat spinal cord. The results suggest that reconstructed MRM(3) chromatograms display significant improvements with the nearly complete elimination of interfering peaks but the sensitivity (i.e. signal-to-noise ratio) was severely reduced. The precision (%CV) observed was between 3.5% and 24.1% using HPLC-MS/MRM and in the range of 4.3-13.1% with HPLC-MS/MRM(3), for SP and NKA. The observed accuracy was within 10% of the theoretical concentrations tested. HPLC-MS/MRM(3) may improve the assay sensitivity to detect difference between samples by reducing significantly the potential of interferences and therefore reduce instrumental errors.

  20. Crosschecking of alpha particle monitor reactions up to 50 MeV

    Takács, S., E-mail: [Institute for Nuclear Research, Hungarian Academy of Sciences, 4026 Debrecen (Hungary); Ditrói, F.; Szűcs, Z. [Institute for Nuclear Research, Hungarian Academy of Sciences, 4026 Debrecen (Hungary); Haba, H.; Komori, Y. [Nishina Center for Accelerator-Based Science, RIKEN, Wako 351-0198 (Japan); Aikawa, M. [Faculty of Science, Hokkaido University, Sapporo 060-0810 (Japan); Nishina Center for Accelerator-Based Science, RIKEN, Wako 351-0198 (Japan); Saito, M. [Graduate School of Science, Hokkaido University, Sapporo 060-0810 (Japan); Nishina Center for Accelerator-Based Science, RIKEN, Wako 351-0198 (Japan)


    Selected reactions with well-defined excitation functions can be used to monitor the parameters of charged particle beams. The frequently used reactions for monitoring alpha particle beams are the {sup 27}Al(α,x){sup 22,24}Na, {sup nat}Ti(α,x){sup 51}Cr, {sup nat}Cu(α,x){sup 66,67}Ga and {sup nat}Cu(α,x){sup 65}Zn reactions. The excitation functions for these reactions were studied using the activation method and stacked target irradiation technique to crosscheck and to compare the above six reactions. Thin metallic foils with natural isotopic composition and well defined thickness were stacked together in sandwich targets and were irradiated at the AVF cyclotron of RIKEN with an alpha particle beam of 51.2 MeV. The activity of the target foils were assessed by using high-resolution gamma spectrometers of high purity Ge detectors. The data sets of the six processes were crosschecked with each other to provide consistent, cross-linked numerical cross section data.

  1. On-line reaction monitoring of lithiation of halogen substituted acetanilides via in situ calorimetry, ATR spectroscopy, and endoscopy.

    Godany, Tamas A; Neuhold, Yorck-Michael; Hungerbühler, Konrad


    Lithiation of N-(4-chlorophenyl)-pivalamide (NCP) and two additional substituted acetanilides: 4-fluoroacetanilide (4-F) and 4-chloroacetanilide (4-Cl) has been monitored by means of calorimetry, on-line ATR-IR and UV/vis spectroscopy and endoscopy. The combined on-line monitoring revealed the differences between the reaction paths of the chosen substrates. Thus the product structure and the reaction times for the individual reaction steps can be determined in situ.

  2. mRM - multiscale Routing Model for Scale-Independent Streamflow Simulations

    Thober, Stephan; Kumar, Rohini; Samaniego, Luis; Mai, Juliane; Rakovec, Oldrich; Cuntz, Matthias


    Routing streamflow through a river network is a basic step within any distributed hydrologic model. It integrates the generated runoff and allows comparison with observed discharge at the outlet of a catchment. The Muskingum routing is a textbook river routing scheme that has been implemented in Earth System Models (e.g., WRF-HYDRO), stand-alone routing schemes (e.g., RAPID) , and hydrologic models (e.g., the mesoscale Hydrologic Model - mHM). Two types of implementations are mostly used. In the first one, the spatial routing resolution is fixed to that of the elevation model irrespective of the hydrologic modeling resolution. This implementation suffers from a high computational demand. In the second one, the spatial resolution is always applied at the hydrologic modelling resolution. This approach requires a scale-independent model behaviour which is often not evaluated. Here, we present the multiscale Routing Model (mRM) that provides a flexible choice of the routing resolution independent of the hydrologic modelling resolution. It incorporates a triangular unit hydrograph for overland flow routing and a Muskingum routing scheme for river routing. mRM provides a scale-independent model behaviour by exploiting the Multiscale Parameter Regionalisation (MPR) included in the open-source mHM ( MPR reflects the structure of the landscape within the parametrisation of hydrologic processes. Effective model parameters are derived by upscaling of high-resolution (i.e., landscape resolution) parameters to the hydrologic modelling/routing resolution as proposed in Samaniego et al. 2010 and Kumar et al. 2013. mRM is coupled in this work to the state-of-the-art land surface model Noah-MP. Simulated streamflow is derived for the Ohio River (≈~525 000 km^2) during the period 1990-2000 at resolutions of 0.0625

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

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


    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.

  4. Monitoring bacterial resistance to chloramphenicol and other antibiotics by liquid chromatography electrospray ionization tandem mass spectrometry using selected reaction monitoring.

    Haag, Anthony M; Medina, Audrie M; Royall, Ariel E; Herzog, Norbert K; Niesel, David W


    Antibiotic resistance is a growing problem worldwide. For this reason, clinical laboratories often determine the susceptibility of the bacterial isolate to a number of different antibiotics in order to establish the most effective antibiotic for treatment. Unfortunately, current susceptibility assays are time consuming. Antibiotic resistance often involves the chemical modification of an antibiotic to an inactive form by an enzyme expressed by the bacterium. Selected reaction monitoring (SRM) has the ability to quickly monitor and identify these chemical changes in an unprecedented time scale. In this work, we used SRM as a technique to determine the susceptibility of several different antibiotics to the chemically modifying enzymes β-lactamase and chloramphenicol acetyltransferase, enzymes used by bacteria to confer resistance to major classes of commonly used antibiotics. We also used this technique to directly monitor the effects of resistant bacteria grown in a broth containing a specific antibiotic. Because SRM is highly selective and can also identify chemical changes in a multitude of antibiotics in a single assay, SRM has the ability to detect organisms that are resistant to multiple antibiotics in a single assay. For these reasons, the use of SRM greatly reduces the time it takes to determine the susceptibility or resistance of an organism to a multitude of antibiotics by eliminating the time-consuming process found in other currently used methods.

  5. When big brother is watching: goal orientation shapes reactions to electronic monitoring during online training.

    Watson, Aaron M; Foster Thompson, Lori; Rudolph, Jane V; Whelan, Thomas J; Behrend, Tara S; Gissel, Amanda L


    Web-based training is frequently used by organizations as a convenient and low-cost way to teach employees new knowledge and skills. As web-based training is typically unproctored, employees may be held accountable to the organization by computer software that monitors their behaviors. The current study examines how the introduction of electronic performance monitoring may provoke negative emotional reactions and decrease learning among certain types of e-learners. Through motivated action theory and trait activation theory, we examine the role of performance goal orientation when e-learners are exposed to asynchronous and synchronous monitoring. We show that some e-learners are more susceptible than others to evaluation apprehension when they perceive their activities are being monitored electronically. Specifically, e-learners higher in avoid performance goal orientation exhibited increased evaluation apprehension if they believed asynchronous monitoring was present, and they showed decreased skill attainment as a result. E-learners higher on prove performance goal orientation showed greater evaluation apprehension if they believed real-time monitoring was occurring, resulting in decreased skill attainment.

  6. The New Zealand Centre for Adverse Reactions Monitoring: a source of practice-based evidence

    Savage R


    Full Text Available The database of the New Zealand Centre for Adverse Reactions Monitoring (CARM is an example of the practice-based evidence discussed in the June issue of the Journal of Primary Health Care. Databases of reported adverse drug reactions (ADRs were established to generate hypotheses to be tested about previously unrecognised adverse reactions and interactions. Occasionally they are sufficient evidence in themselves. They can also identify prescribing practices that might increase the potential for ADRs to occur and provide feedback into guidelines in terms of the consequences of their use or non-use. Well-documented ADR reports can also highlight risk factors, thus providing a valuable contribution to risk benefit assessments in individual patients. Examples are discussed that support the use of ADRs as practice-based evidence in a non-hierarchical system in which case reports and case series, observational studies and randomised clinical trials contribute in a flexible relationship depending on the issue under investigation.

  7. 液质联用多反应监测法定量目标多肽或蛋白质%Quantification of Target Peptides or Proteins by Liquid ChromatographyMass Spectrometry with Multiple Reaction Monitoring

    刘永福; 贾小芳; 腾珍林; 尹林; 刘保池; 张丽军


    为建立优化的血浆内源性多肽提取方法,并且构建目标多肽和蛋白质的质谱定量方法,本研究考察了超滤法、有机溶剂沉淀法和固相萃取法对血浆内源性多肽的提取效果,并通过Tricine-SDS-PAGE对提取效果进行比较.通过液相色谱串联质谱多反应监测(MRM)分析,建立了多肽标准品ESAT-6定量方法,并将ESAT-6定量建立的液相色谱和质谱条件应用于蛋白质的定量,对多肽和蛋白质MRM定量的标准曲线进行了考察.Tricine-SDS-PAGE结果表明,乙腈沉淀法是最佳的血浆内源性多肽提取方法,低分子量的多肽可以得到很好的富集,且能有效地去除高分子蛋白质的污染.液相色谱串联质谱MRM法检测血浆内提取的多肽,标准曲线的线性较好,相关系数为0.999.另外,采用MRM法对胶内分离的蛋白质进行定量,标准曲线的线性相关系数为0.995.综上所述,本研究构建了一种简单有效的血浆多肽提取方法,通过液质联用MRM法成功地实现了目标多肽和蛋白质定量测定.该定量方法可以推广应用于复杂样品中的多肽和蛋白质的定量分析.%This study was to establish a modified plasma peptide extraction method and to develop a mass spectrometry quantification method for target peptides or proteins. Three techniques of ultrafiltration, organic solvent extraction and solid phase extraction were used to extract peptides from plasma samples. Tricine-SDS-PAGE was used to determine the extraction efficiency. Peptide and protein quantification were completed by liquid chromatography combined with mass spectrometry in multiple reaction monitoring (MRM) mode. The Tricine-SDS-PAGE results showed that acetonitrile (CAN) precipitation was the most efficient approach for low molecular plasma peptides enrichment besides for excluding the high molecular protein contaminations. The correlation coefficients of the standard curves were 0. 995 and 0. 999 in the quantification of

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

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


    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.

  9. Optical fiber sensor for an on-line monitoring of epoxy resin/amine reaction

    Fouchal, F.; Knight, J. A. G.; Garrington, N.; Cope, B.


    An optical fiber sensor is described; it permits a rapid determination of the state of chemical reaction in epoxy resin diglycidyl ether of bisphenol A (DGEBA), and Triethylenetetramine stoichiometric reaction. Mid infrared Fourier transform technique was used to analyze the mixture via a pair of embedded optical fibers connected to an FTIR spectrometer, which operates in the region 4000-700 cm-1 of the electromagnetic waves. An accurate monitoring of the concentration changes over time of epoxy, amine and hydroxyl groups gave a good estimate of extent of reaction and description of physical state of the produced matrix. The chemical group peaks 1130 cm-1 and 3300-3400 cm-1 where used to follow the disappearance of the epoxy, and the amine respectively, while the peak 2970 cm-1 was used as reference peak. A review of a number of other techniques used to study the curing of epoxy resins together with on-line monitoring methods applied in processing thermoset resin is referred to.

  10. Interfacing supercritical fluid reaction apparatus with on-line liquid chromatography: monitoring the progress of a synthetic organic reaction performed in supercritical fluid solution.

    Ramsey, Edward D; Li, Ben; Guo, Wei; Liu, Jing Y


    An interface has been developed that connects a supercritical fluid reaction (SFR) vessel directly on-line to a liquid chromatograph. The combined SFR-LC system has enabled the progress of the esterification reaction between phenol and benzoyl chloride to synthesize phenyl benzoate in supercritical fluid carbon dioxide solution to be dynamically monitored. This was achieved by the periodic SFR-LC analysis of samples directly withdrawn from the esterification reaction mixture. Using the series of SFR-LC analysis results obtained for individual esterification reactions, the reaction progress profile for each esterification reaction was obtained by expressing the measured yield of phenyl benzoate as a function of reaction time. With reaction temperature fixed at 75°C, four sets (n=3) of SFR-LC reaction progress profiles were obtained at four different SFR pressures ranging from 13.79 to 27.58 MPa. The maximum SFR yield obtained for phenyl benzoate using a standard set of reactant concentrations was 85.2% (R.S.D. 4.2%) when the reaction was performed at 13.79 MPa for 90 min. In comparison, a phenyl benzoate yield of less than 0.3% was obtained using the same standard reactant concentrations after 90 min reaction time at 75°C using either: heptane, ethyl acetate or acetonitrile as conventional organic reaction solvents.

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

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


    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 analysis of

  12. Direct monitoring of the strand passage reaction of DNA topoisomerase II triggers checkpoint activation.

    Katherine L Furniss

    Full Text Available By necessity, the ancient activity of type II topoisomerases co-evolved with the double-helical structure of DNA, at least in organisms with circular genomes. In humans, the strand passage reaction of DNA topoisomerase II (Topo II is the target of several major classes of cancer drugs which both poison Topo II and activate cell cycle checkpoint controls. It is important to know the cellular effects of molecules that target Topo II, but the mechanisms of checkpoint activation that respond to Topo II dysfunction are not well understood. Here, we provide evidence that a checkpoint mechanism monitors the strand passage reaction of Topo II. In contrast, cells do not become checkpoint arrested in the presence of the aberrant DNA topologies, such as hyper-catenation, that arise in the absence of Topo II activity. An overall reduction in Topo II activity (i.e. slow strand passage cycles does not activate the checkpoint, but specific defects in the T-segment transit step of the strand passage reaction do induce a cell cycle delay. Furthermore, the cell cycle delay depends on the divergent and catalytically inert C-terminal region of Topo II, indicating that transmission of a checkpoint signal may occur via the C-terminus. Other, well characterized, mitotic checkpoints detect DNA lesions or monitor unattached kinetochores; these defects arise via failures in a variety of cell processes. In contrast, we have described the first example of a distinct category of checkpoint mechanism that monitors the catalytic cycle of a single specific enzyme in order to determine when chromosome segregation can proceed faithfully.

  13. Time resolved bovine host reponse to virulence factors mapped in milk by selected reaction monitoring

    Bislev, Stine Lønnerup; Kusebauch, Ulrike; Codrea, Marius Cosmin

    in food production. Rapid diagnostic methods are still not available, and particularly pathogen-specific biomarkers would be highly valuable, as these may allow correct antibiotic treatment to be applied shortly after an udder infection has been observed. Moreover, with automatic milking systems and on-line....... Furthermore, this SRM approach provides a strong tool for investigating these proteins in very large scale experiments, particularly with the scope to investigate whether these candidate biomarkers are suited for monitoring animal health in milk production.......TIME RESOLVED BOVINE HOST RESPONSE TO VIRULENCE FACTORS, MAPPED IN MILK BY SELECTED REACTION MONITORING S.L. Bislev1, U. Kusebauch2, M.C. Codrea1, R. Moritz2, C.M. Røntved1, E. Bendixen1 1 Department of Animal Science, Faculty of Science and Technology, Aarhus University, Tjele, Denmark; 2...

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

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


    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...

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

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


    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

  16. A Demonstration of Concrete Structural Health Monitoring Framework for Degradation due to Alkali-Silica Reaction

    Mahadevan, Sankaran [Idaho National Lab. (INL), Idaho Falls, ID (United States); Agarwal, Vivek [Idaho National Lab. (INL), Idaho Falls, ID (United States); Neal, Kyle [Idaho National Lab. (INL), Idaho Falls, ID (United States); Nath, Paromita [Idaho National Lab. (INL), Idaho Falls, ID (United States); Bao, Yanqing [Idaho National Lab. (INL), Idaho Falls, ID (United States); Cai, Guowei [Idaho National Lab. (INL), Idaho Falls, ID (United States); Orme, Peter [Idaho National Lab. (INL), Idaho Falls, ID (United States); Adams, Douglas [Idaho National Lab. (INL), Idaho Falls, ID (United States); Kosson, David [Idaho National Lab. (INL), Idaho Falls, ID (United States)


    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 ongoing research project is seeking to develop a probabilistic framework for health diagnosis and prognosis of aging concrete structures in a nuclear power plant that is subjected to physical, chemical, environment, and mechanical degradation. The proposed framework consists of four elements: monitoring, data analytics, uncertainty quantification and prognosis. This report focuses on degradation caused by ASR (alkali-silica reaction). Controlled specimens were prepared to develop accelerated ASR degradation. Different monitoring techniques – thermography, digital image correlation (DIC), mechanical deformation measurements, nonlinear impact resonance acoustic spectroscopy (NIRAS), and vibro-acoustic modulation (VAM) -- were used to detect the damage caused by ASR. Heterogeneous data from the multiple techniques was used for damage diagnosis and prognosis, and quantification of the associated uncertainty using a Bayesian network approach. Additionally, MapReduce technique has been demonstrated with synthetic data. This technique can be used in future to handle large amounts of observation data obtained from the online monitoring of realistic structures.

  17. On-line monitoring of the transesterification reaction between triglycerides and ethanol using near infrared spectroscopy combined with gas chromatography.

    Richard, Romain; Li, Ying; Dubreuil, Brigitte; Thiebaud-Roux, Sophie; Prat, Laurent


    Many analytical procedures have been developed to determine the composition of reaction mixtures during transesterification of vegetable oils with alcohols. However, despite their accuracy, these methods are time consuming and cannot be easily used for on-line monitoring. In this work, a fast analytical method was developed to on-line monitor the transesterification reaction of high oleic sunflower oil with ethanol using Near InfraRed spectroscopy and a multivariate approach. The reactions were monitored through sequential scans of the reaction medium with a probe in a one-liter batch reactor without collecting and preparing samples. To calibrate the NIR analytical method, gas chromatography-flame ionization detection was used as a reference method. The method was validated by studying the kinetics of the EtONa-catalyzed transesterification reaction. Activation energy (51.0 kJ/mol) was also determined by considering a pseudo second order kinetics model. Copyright © 2011 Elsevier Ltd. All rights reserved.

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

    Agarwal, Vivek [Idaho National Lab. (INL), Idaho Falls, ID (United States); Cai, Guowei [Idaho National Lab. (INL), Idaho Falls, ID (United States); Gribok, Andrei V. [Idaho National Lab. (INL), Idaho Falls, ID (United States); Mahadevan, Sankaran [Idaho National Lab. (INL), Idaho Falls, ID (United States)


    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.

  19. Parallel reaction monitoring using quadrupole-Orbitrap mass spectrometer: Principle and applications.

    Bourmaud, Adele; Gallien, Sebastien; Domon, Bruno


    Targeted mass spectrometry-based approaches are nowadays widely used for quantitative proteomics studies and more recently have been implemented on high resolution/accurate mass (HRAM) instruments resulting in a considerable performance improvement. More specifically, the parallel reaction monitoring technique (PRM) performed on quadrupole-Orbitrap mass spectrometers, leveraging the high resolution and trapping capabilities of the instrument, offers a clear advantage over the conventional selected reaction monitoring (SRM) measurements executed on triple quadrupole instruments. Analyses performed in HRAM mode allow for an improved discrimination between signals derived from analytes and those resulting from matrix interferences translating in the reliable quantification of low abundance components. The purpose of the study defines various implementation schemes of PRM, namely: (i) exploratory experiments assessing the detectability of very large sets of peptides (100-1000), (ii) wide-screen analyses using (crude) internal standards to obtain statistically meaningful (relative) quantitative analyses, and (iii) precise/accurate quantification of a limited number of analytes using calibrated internal standards. Each of the three implementation schemes requires specific acquisition methods with defined parameters to appropriately control the acquisition during the actual peptide elution. This tutorial describes the different PRM approaches and discusses their benefits and limitations in terms of quantification performance and confidence in analyte identification.

  20. Real-time and in situ monitoring of mechanochemical milling reactions.

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


    Chemical and structural transformations have long been carried out by milling. Such mechanochemical steps are now ubiquitous in a number of industries (such as the pharmaceutical, chemical and metallurgical industries), and are emerging as excellent environmentally friendly alternatives to solution-based syntheses. However, mechanochemical transformations are typically difficult to monitor in real time, which leaves a large gap in the mechanistic understanding required for their development. We now report the real-time study of mechanochemical transformations in a ball mill by means of in situ diffraction of high-energy synchrotron X-rays. Focusing on the mechanosynthesis of metal-organic frameworks, we have directly monitored reaction profiles, the formation of intermediates, and interconversions of framework topologies. Our results reveal that mechanochemistry is highly dynamic, with reaction rates comparable to or greater than those in solution. The technique also enabled us to probe directly how catalytic additives recently introduced in the mechanosynthesis of metal-organic frameworks, such as organic liquids or ionic species, change the reactivity pathways and kinetics.

  1. A Reversible Nanolamp for Instantaneous Monitoring of Cyanide Based on an Elsner-Like Reaction.

    Qing, Zhihe; Hou, Lina; Yang, Le; Zhu, Lixuan; Yang, Sheng; Zheng, Jing; Yang, Ronghua


    It is well-known that cyanide ion (CN(-)) is a hypertoxic anion, which can cause adverse effects in both the environment and living beings; thus, it is highly desirable to develop strategies for detecting CN(-), especially in water and food. However, due to the short half-life of free cyanide, long analysis time and/or interference from other competitive ions are general challenges for accurate monitoring of CN(-). In this work, through the investigation on the sequence-dependent optical interaction of DNA-CuNPs with the fluorophore (e.g., EBMVC-B), we found, for the first time, that DNA-CuNPs were an ideal alternative as fluorescence quencher in constructing a sensor which could be illuminated by CN(-) based on an Elsner-like reaction and that the signal switching was dependent on poly(AT/TA) dsDNA sequence. By virtue of CuNPs' small size and its high chemical reactivity with cyanide, the lighting of fluorescence was ultrarapid and similar to the hairtrigger "turn-on" of a lamp, which is significant for accurately monitoring a target of short half-life (e.g., cyanide). Attributed to the unique Elsner-like reaction between CN(-) and the Cu atoms, high selectivity was achieved for CN(-) monitoring by the nanolamp, with practical applications in real water and food samples. In addition, because of the highly efficient in situ formation of DNA-CuNPs and the approximative stoichiometry between CN(-) and Cu(2+) in the fluorescence switching, the nanolamp could be reversibly turned on and off through the alternate regulation of CN(-) and Cu(2+), displaying potential for developing reusable nanosensors and constructing optical molecular logic circuits.

  2. Reaction monitoring of toluenediisocyanate (TDI) polymerization on a non-mixable aqueous surface by MALDI mass spectrometry.

    Ahn, Yeong Hee; Kim, Ji Seok; Kim, Sung Ho


    The polymerization reaction of toluene diisocyanate (TDI) and hydroxyl compounds has been widely used for the production of polyurea resins. Since the composition and molecular-weight distribution of polymer adducts greatly influence the final properties of the resuting polymer, the development of analytical tools capable of monitoring the polyaddition reactions is important to control them as well as the properties of the resuting polymer. Here we report that matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI TOF MS) is useful to precisely monitor time-dependent dynamic events occurring in the polymerization reaction of TDI with water. For this purpose, the polymerization reactions were conducted in two different reaction systems, continuously supplying sufficient water and depleting water after an initial exposure of water to provide an anhydrous storage condition of prepolymer adducts. Samples prepared in a time course from the two different reaction systems were analyzed by a MALDI TOF mass spectrometer. The polymerization adducts of TDI and water were monitored and showed to consist of three structural types of polymer adduct series, including diisocyanate, monoamino, and diamino series. These MALDI mass data efficiently reflected changes in the reaction conditions of each TDI polymerization reaction, thereby providing precise information at the molecular level for time-dependent events occurring during the polymerization reaction. These events included changes between the polymer adduct series and in the molecular-weight distribution of each polymer adduct series. The results obtained in this study suggest that high-throughput MALDI MS-based dynamic monitoring of polymerization can be used to precisely control the polymerization reaction as well as to rapidly monitor the state of prepolymers in storage.

  3. Monitoring Chemical and Biological Electron Transfer Reactions with a Fluorogenic Vitamin K Analogue Probe.

    Belzile, Mei-Ni; Godin, Robert; Durantini, Andrés M; Cosa, Gonzalo


    We report herein the design, synthesis, and characterization of a two-segment fluorogenic analogue of vitamin K, B-VKQ, prepared by coupling vitamin K3, also known as menadione (a quinone redox center), to a boron-dipyrromethene (BODIPY) fluorophore (a lipophilic reporter segment). Oxidation-reduction reactions, spectroelectrochemical studies, and enzymatic assays conducted in the presence of DT-diaphorase illustrate that the new probe shows reversible redox behavior on par with that of vitamin K, provides a high-sensitivity fluorescence signal, and is compatible with biological conditions, opening the door to monitor remotely (i.e., via imaging) redox processes in real time. In its oxidized form, B-VKQ is non-emissive, while upon reduction to the hydroquinone form, B-VKQH2, BODIPY fluorescence is restored, with emission quantum yield values of ca. 0.54 in toluene. Density functional theory studies validate a photoinduced electron transfer intramolecular switching mechanism, active in the non-emissive quinone form and deactivated upon reduction to the emissive dihydroquinone form. Our results highlight the potential of B-VKQ as a fluorogenic probe to study electron transfer and transport in model systems and biological structures with optimal sensitivity and desirable chemical specificity. Use of such a probe may enable a better understanding of the role that vitamin K plays in biological redox reactions ubiquitous in key cellular processes, and help elucidate the mechanism and pathological significance of these reactions in biological systems.

  4. Quantitative determination of free D-Asp, L-Asp and N-methyl-D-aspartate in mouse brain tissues by chiral separation and Multiple Reaction Monitoring tandem mass spectrometry.

    Fontanarosa, Carolina; Pane, Francesca; Sepe, Nunzio; Pinto, Gabriella; Trifuoggi, Marco; Squillace, Marta; Errico, Francesco; Usiello, Alessandro; Pucci, Piero; Amoresano, Angela


    Several studies have suggested that free d-Asp has a crucial role in N-methyl d-Asp receptor-mediated neurotransmission playing very important functions in physiological and pathological processes. This paper describes the development of an analytical procedure for the direct and simultaneous determination of free d-Asp, l-Asp and N-methyl d-Asp in specimens of different mouse brain tissues using chiral LC-MS/MS in Multiple Reaction Monitoring scan mode. After comparing three procedures and different buffers and extraction solvents, a simple preparation procedure was selected the analytes of extraction. The method was validated by analyzing l-Asp, d-Asp and N-methyl d-Asp recovery at different spiked concentrations (50, 100 and 200 pg/μl) yielding satisfactory recoveries (75-110%), and good repeatability. Limits of detection (LOD) resulted to be 0.52 pg/μl for d-Asp, 0.46 pg/μl for l-Asp and 0.54 pg/μl for NMDA, respectively. Limits of quantification (LOQ) were 1.57 pg/μl for d-Asp, 1.41 pg/μl for l-Asp and 1.64 pg/μl for NMDA, respectively. Different concentration levels were used for constructing the calibration curves which showed good linearity. The validated method was then successfully applied to the simultaneous detection of d-Asp, l-Asp and NMDA in mouse brain tissues. The concurrent, sensitive, fast, and reproducible measurement of these metabolites in brain tissues will be useful to correlate the amount of free d-Asp with relevant neurological processes, making the LC-MS/MS MRM method well suited, not only for research work but also for clinical analyses.

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

    Silva Elipe, Maria Victoria; Milburn, Robert R


    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.

  6. Time resolved bovine host reponse to virulence factors mapped in milk by selected reaction monitoring

    Bislev, Stine Lønnerup; Kusebauch, Ulrike; Codrea, Marius Cosmin

    TIME RESOLVED BOVINE HOST RESPONSE TO VIRULENCE FACTORS, MAPPED IN MILK BY SELECTED REACTION MONITORING S.L. Bislev1, U. Kusebauch2, M.C. Codrea1, R. Moritz2, C.M. Røntved1, E. Bendixen1 1 Department of Animal Science, Faculty of Science and Technology, Aarhus University, Tjele, Denmark; 2...... Institute for Systems Biology, Seattle, Washington, USA Mastitis is beyond doubt the largest health problem in modern milk production. Many different pathogens can cause infections in the mammary gland, and give rise to severe toll on animal welfare, economic gain as well as on excessive use of antibiotics...... in food production. Rapid diagnostic methods are still not available, and particularly pathogen-specific biomarkers would be highly valuable, as these may allow correct antibiotic treatment to be applied shortly after an udder infection has been observed. Moreover, with automatic milking systems and on...

  7. Targeted proteomics by selected reaction monitoring mass spectrometry: applications to systems biology and biomarker discovery.

    Elschenbroich, Sarah; Kislinger, Thomas


    Mass Spectrometry-based proteomics is now considered a relatively established strategy for protein analysis, ranging from global expression profiling to the identification of protein complexes and specific post-translational modifications. Recently, Selected Reaction Monitoring Mass Spectrometry (SRM-MS) has become increasingly popular in proteome research for the targeted quantification of proteins and post-translational modifications. Using triple quadrupole instrumentation (QqQ), specific analyte molecules are targeted in a data-directed mode. Used routinely for the quantitative analysis of small molecular compounds for at least three decades, the technology is now experiencing broadened application in the proteomics community. In the current review, we will provide a detailed summary of current developments in targeted proteomics, including some of the recent applications to biological research and biomarker discovery.

  8. Adverse drug reaction monitoring of newer oral anti diabetic drugs – a pharmacovigilance perspective

    Ankita Bhattacharjee


    Full Text Available Objective: To monitor and evaluate adverse drug reactions (ADRs of newer oral anti-diabetic drugs in type II diabetics by spontaneous/solicited ADR monitoring.Material and methods: Two hundred and thirty two diabetic patients on newer oral antidiabetic drugs were evaluated prospectively in a cross-sectional study over a period of eighteen months. All patients were followed up for ADRs which were evaluated for incidence, frequency, severity and causality. ADR severity was graded according to University of Virginia Health System Adverse Drug Reaction Reporting program criteria and causality assessment was done using WHO-UMC scale.Results: 190 out of 232 patients (42 patients lost to follow up were evaluated. ADRs were observed in 34 cases (17.9%. Most common ADRs were gastrointestinal (44.2% followed by musculoskeletal (17.6%, metabolic (14.7%, infections (5.9% and others (17.6%. The maximal frequency of ADRs was seen with sitagliptin (6.4% followed by vildagliptin(3.8%, saxagliptin(2.7%, saroglitazar(2.1%, linagliptin(1.6%, canagliflozin(1.6%. 25(73.5%, 8(23.5% and 1(3% ADRs were mild, moderate and severe respectively. 24(70% ADRs were classified as possible, 9(27% probable and 1(3% unlikely on causality assessment. Conclusion: Newer oral antidiabetic drugs like gliptins and SGLT-2 inhibitors have potential to cause ADRs. Gastro-intestinal, musculoskeletal, metabolic were most common ADRs. Active pharmacovigilance should be carried out for risk identification and management. 

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

    Tsuchiya, Hikaru; Tanaka, Keiji, E-mail:; Saeki, Yasushi, E-mail:


    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.

  10. In-situ nanoelectrospray for high-throughput screening of enzymes and real-time monitoring of reactions.

    Yang, Yuhan; Han, Feifei; Ouyang, Jin; Zhao, Yunling; Han, Juan; Na, Na


    The in-situ and high-throughput evaluation of enzymes and real-time monitoring of enzyme catalyzed reactions in liquid phase is quite significant in the catalysis industry. In-situ nanoelectrospray, the direct sampling and ionization method for mass spectrometry, has been applied for high-throughput evaluation of enzymes, as well as the on-line monitoring of reactions. Simply inserting a capillary into a liquid system with high-voltage applied, analytes in liquid reaction system can be directly ionized at the capillary tip with small volume consumption. With no sample pre-treatment or injection procedure, different analytes such as saccharides, amino acids, alkaloids, peptides and proteins can be rapidly and directly extracted from liquid phase and ionized at the capillary tip. Taking irreversible transesterification reaction of vinyl acetate and ethanol as an example, this technique has been used for the high-throughput evaluation of enzymes, fast optimizations, as well as real-time monitoring of reaction catalyzed by different enzymes. In addition, it is even softer than traditional electrospray ionization. The present method can also be used for the monitoring of other homogenous and heterogeneous reactions in liquid phases, which will show potentials in the catalysis industry.

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

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


    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.

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

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


    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.

  13. Light-induced reactions of Escherichia coli DNA photolyase monitored by Fourier transform infrared spectroscopy.

    Schleicher, Erik; Hessling, Benedikt; Illarionova, Viktoria; Bacher, Adelbert; Weber, Stefan; Richter, Gerald; Gerwert, Klaus


    Cyclobutane-type pyrimidine dimers generated by ultraviolet irradiation of DNA can be cleaved by DNA photolyase. The enzyme-catalysed reaction is believed to be initiated by the light-induced transfer of an electron from the anionic FADH- chromophore of the enzyme to the pyrimidine dimer. In this contribution, first infrared experiments using a novel E109A mutant of Escherichia coli DNA photolyase, which is catalytically active but unable to bind the second cofactor methenyltetrahydrofolate, are described. A stable blue-coloured form of the enzyme carrying a neutral FADH radical cofactor can be interpreted as an intermediate analogue of the light-driven DNA repair reaction and can be reduced to the enzymatically active FADH- form by red-light irradiation. Difference Fourier transform infrared (FT-IR) spectroscopy was used to monitor vibronic bands of the blue radical form and of the fully reduced FADH- form of the enzyme. Preliminary band assignments are based on experiments with 15N-labelled enzyme and on experiments with D2O as solvent. Difference FT-IR measurements were also used to observe the formation of thymidine dimers by ultraviolet irradiation and their repair by light-driven photolyase catalysis. This study provides the basis for future time-resolved FT-IR studies which are aimed at an elucidation of a detailed molecular picture of the light-driven DNA repair process.

  14. A low power sub- μW chemical gilbert cell for ISFET differential reaction monitoring.

    Kalofonou, Melpomeni; Toumazou, Christofer


    This paper presents a low power current-mode method for monitoring differentially derived changes in pH from ion-sensitive field-effect transistor (ISFET) sensors, by adopting the Chemical Gilbert Cell. The fabricated system, with only a few transistors, achieves differential measurements and therefore drift minimisation of continuously recorded pH signals obtained from biochemical reactions such as DNA amplification in addition to combined gain tunability using only a single current. Experimental results are presented, demonstrating the capabilities of the front-end at a microscopic level through integration in a lab-on-chip (LoC) setup combining a microfluidic assembly, suitable for applications that require differential monitoring in small volumes, such as DNA detection where more than one gene needs to be studied. The system was designed and fabricated in a typical 0.35 μ m CMOS process with the resulting topology achieving good differential pH sensitivity with a measured low power consumption of only 165 nW due to weak inversion operation. A tunable gain is demonstrated with results confirming 15.56 dB gain at 20 nA of ISFET bias current and drift reduction of up to 100 times compared to a single-ended measurement is also reported due to the differential current output, making it ideal for robust, low-power chemical measurement.

  15. Spontaneous monitoring of adverse reactions to drugs by Italian dermatologists: a pilot study. Gruppo Italiano Studi Epidemiologici in Dermatologia.


    During 1988, the Gruppo Italiano Studi Epidemiologici in Dermatologia (GISED) coordinated a pilot study aimed at evaluating the feasibility of a system for spontaneous monitoring of adverse drug reactions in dermatological practice in Italy. Approximately 400 dermatologists were asked to collaborate, and 141 agreed to the study. Procedures similar to those well established in other surveillance programs (including the use of standard forms and standardized assessment procedure) were adopted. In a 2-month period 775 reports were collected, of which 711 were maintained after careful evaluation. The general profile of the adverse reactions reported was in accordance with the experience derived by other spontaneous surveillance programs. The main purpose of spontaneous reporting systems is the identification of new reactions, and a model analysis was proposed, in our study, with reference to skin reactions to bamifylline. The demonstration of the feasibility of a drug-monitoring program in Italy, where little tradition exists in the area, is the most important result of our study.

  16. Noncovalent chirality sensing ensembles for the detection and reaction monitoring of amino acids, peptides, proteins, and aromatic drugs.

    Biedermann, Frank; Nau, Werner M


    Ternary complexes between the macrocyclic host cucurbit[8]uril, dicationic dyes, and chiral aromatic analytes afford strong induced circular dichroism (ICD) signals in the near-UV and visible regions. This allows for chirality sensing and peptide-sequence recognition in water at low micromolar analyte concentrations. The reversible and noncovalent mode of binding ensures an immediate response to concentration changes, which allows the real-time monitoring of chemical reactions. The introduced supramolecular method is likely to find applications in bioanalytical chemistry, especially enzyme assays, for drug-related analytical applications, and for continuous monitoring of enantioselective reactions, particularly asymmetric catalysis.

  17. Diagnostic value of preoperative contrast-enhanced MR imaging of the breast; Diagnostischer Stellenwert der praeoperativen MR-Mammographie (MRM)

    Winnekendonk, G.; Krug, B.; Lackner, K. [Inst. und Poliklinik fuer Radiologische Diagnostik der Univ. zu Koeln (Germany); Warm, M.; Goehring, U.J.; Mallmann, P. [Klinik und Poliklinik fuer Frauenheilkunde und Geburtshilfe der Univ. zu Koeln (Germany)


    Purpose: to evaluate preoperative contrast enhanced MR imaging in clinically, mammographically and/or ultrasonographically established breast cancer. Materials and method: from September 1998 to August 1999, preoperative contrast-enhanced MR imaging of the breast was performed in 91 patients with lesions highly suggestive of malignancy (BIRADS IV and V) by clinical, mammographic, and/or ultrasonographic criteria. MR imaging findings were postsurgically correlated with other imaging, intraoperative and histopathologic results. Results: histopathologic analysis revealed 61 (66%) malignant and 31 (34%) benign lesions. In 63 (69%) of the 91 investigated patients, MR mammographies were classified as tumor suspect and in the remaining 28 (31%) cases as benign. The sensitivity, specificity and accuracy were 90%, 67% and 81% for contrast-enhanced MR imaging. Additional tumor manifestations (multifocal or multicentric disease, contralateral carcinoma) were found by MR imaging alone in 10 patients (11%). Conclusion: contrast-enhanced MR imaging may reveal unsuspected multifocal, multicentric or contralateral breast carcinoma that changes the surgical therapy if the intention is total tumor removal. The prognostic role of a potentially more radical surgical therapy on the basis of these findings is not clear. (orig.) [German] Fragestellung: lst der praeoperative Einsatz der MR-Mammographie (MRM) bei palpatorischem, sonographischem und/oder roentgenmammographischem Tumorverdacht sinnvoll? Material und Methoden: Vom 1.9.1998 bis zum 31.8.1999 wurde konsekutiv bei allen Patientinnen, bei denen aufgrund eines palpatorischen, roentgenmammographischen (BIRADS IV und V) und/oder sonographischen Malignomverdachtes die Indikation zur Operation bestand, praeoperativ eine MRM angefertigt. Die Ergebnisse der MRM wurden postoperativ mit dem Operationsbefund und den histologischen Ergebnissen verglichen. Ergebnisse: Bei den 91 operierten Patientinnen wurden histologisch 61 Karzinome (66

  18. Monitoring the inorganic chemical reaction by surface-enhanced Raman spectroscopy: A case of Fe³⁺ to Fe²⁺ conversion.

    Qin, Suhua; Meng, Juan; Tang, Xianghu; Yang, Liangbao


    Monitoring the process of organic chemical reactions to study the kinetics by surface-enhanced Raman spectroscopy (SERS) is currently of immense interest. However, monitoring the inorganic chemical reaction is still an extremely difficulty for researchers. This study exactly focused on the monitor of inorganic chemical reaction. Capillary coated with silver nanoparticles was introduced, which was an efficient platform for monitoring reactions with SERS due to the advantages of sensitivity and excellent reproducibility. The photoreduction of [Fe(phen)3](3+) to [Fe(phen)3](2+) was used as model reaction to demonstrated the feasibility of SERS monitoring inorganic chemical reaction by involving in metal-organic complexes. Moreover, the preliminary implementation demonstrated that the kinetics of photoreduction can be real-time monitored by in situ using the SERS technique on a single constructed capillary, which may be useful for the practical application of SERS technique.

  19. Adverse drug reactions monitoring of psychotropic drugs: a tertiary care centre study

    Hemendra Singh


    Full Text Available Background: Many new psychotropic drugs/ agents have been developed and found to be effective in the treatment of psychiatric disorders. However, these drugs also exhibit adverse drug reactions (ADRs which may affect compliance in psychiatric patients. Hence the present study was aimed at monitoring and assessing ADRs caused by psychotropic drugs. Methods: A hospital based prospective observational study was carried out in the psychiatry outpatient department of a tertiary care teaching hospital for the duration of six months. Two hundred and two patients were included in the study and ADRs were documented using a predesigned data collection form. The causality assessment was carried out as per the criteria of both the World Health Organization- Uppsala Monitoring Centre (WHO-UMC and Naranjo scale. Severity and predictability assessment of ADRs were also performed. Results: A total of 106 ADRs were observed during the study period with majority of them occurring in 25-35 years of age group (40.56%. Weight gain (18.86% followed by sedation (16.03% and insomnia (11.32% were found to be the commonest ADRs. Risperidone (19.8% and escitalopram (12.3% were the drugs responsible for majority of the ADRs. Causality assessment showed that most of ADRs were possible and probable. 94.33% of ADRs were found to be mild and 89% of them were predictable. Conclusion: A wide range of ADRs affecting central nervous and metabolic systems were reported with psychotropic drugs. The study findings necessitate the need for an active pharmacovigilance programme for the safe and effective use of psychotropics.

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

    Jennifer M Neugebauer

    Full Text Available 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.

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

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


    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).


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


    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

  3. Protein turnover measurement using selected reaction monitoring-mass spectrometry (SRM-MS).

    Holman, Stephen W; Hammond, Dean E; Simpson, Deborah M; Waters, John; Hurst, Jane L; Beynon, Robert J


    Protein turnover represents an important mechanism in the functioning of cells, with deregulated synthesis and degradation of proteins implicated in many diseased states. Therefore, proteomics strategies to measure turnover rates with high confidence are of vital importance to understanding many biological processes. In this study, the more widely used approach of non-targeted precursor ion signal intensity (MS1) quantification is compared with selected reaction monitoring (SRM), a data acquisition strategy that records data for specific peptides, to determine if improved quantitative data would be obtained using a targeted quantification approach. Using mouse liver as a model system, turnover measurement of four tricarboxylic acid cycle proteins was performed using both MS1 and SRM quantification strategies. SRM outperformed MS1 in terms of sensitivity and selectivity of measurement, allowing more confident determination of protein turnover rates. SRM data are acquired using cheaper and more widely available tandem quadrupole mass spectrometers, making the approach accessible to a larger number of researchers than MS1 quantification, which is best performed on high mass resolution instruments. SRM acquisition is ideally suited to focused studies where the turnover of tens of proteins is measured, making it applicable in determining the dynamics of proteins complexes and complete metabolic pathways.This article is part of the themed issue 'Quantitative mass spectrometry'.

  4. Automated selected reaction monitoring software for accurate label-free protein quantification.

    Teleman, Johan; Karlsson, Christofer; Waldemarson, Sofia; Hansson, Karin; James, Peter; Malmström, Johan; Levander, Fredrik


    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.

  5. Towards continuous and real-time attention monitoring at work: reaction time versus brain response.

    Mijović, Pavle; Ković, Vanja; De Vos, Maarten; Mačužić, Ivan; Todorović, Petar; Jeremić, Branislav; Gligorijević, Ivan


    Continuous and objective measurement of the user attention state still represents a major challenge in the ergonomics research. Recently available wearable electroencephalography (EEG) opens new opportunities for objective and continuous evaluation of operators' attention, which may provide a new paradigm in ergonomics. In this study, wearable EEG was recorded during simulated assembly operation, with the aim to analyse P300 event-related potential component, which provides reliable information on attention processing. In parallel, reaction times (RTs) were recorded and the correlation between these two attention-related modalities was investigated. Negative correlation between P300 amplitudes and RTs has been observed on the group level (p attention monitoring in ergonomics research. On the other hand, no significant correlation between RTs and P300 latency was found on group, neither on individual level. Practitioner Summary: Ergonomic studies of assembly operations mainly investigated physical aspects, while mental states of the assemblers were not sufficiently addressed. Presented study aims at attention tracking, using realistic workplace replica. It is shown that drops in attention could be successfully traced only by direct brainwave observation, using wireless electroencephalographic measurements.

  6. Oxidized fatty acid analysis by charge-switch derivatization, selected reaction monitoring, and accurate mass quantitation.

    Liu, Xinping; Moon, Sung Ho; Mancuso, David J; Jenkins, Christopher M; Guan, Shaoping; Sims, Harold F; Gross, Richard W


    A highly sensitive, specific, and robust method for the analysis of oxidized metabolites of linoleic acid (LA), arachidonic acid (AA), and docosahexaenoic acid (DHA) was developed using charge-switch derivatization, liquid chromatography-electrospray ionization tandem mass spectrometry (LC-ESI MS/MS) with selected reaction monitoring (SRM) and quantitation by high mass accuracy analysis of product ions, thereby minimizing interferences from contaminating ions. Charge-switch derivatization of LA, AA, and DHA metabolites with N-(4-aminomethylphenyl)-pyridinium resulted in a 10- to 30-fold increase in ionization efficiency. Improved quantitation was accompanied by decreased false positive interferences through accurate mass measurements of diagnostic product ions during SRM transitions by ratiometric comparisons with stable isotope internal standards. The limits of quantitation were between 0.05 and 6.0pg, with a dynamic range of 3 to 4 orders of magnitude (correlation coefficient r(2)>0.99). This approach was used to quantitate the levels of representative fatty acid metabolites from wild-type (WT) and iPLA2γ(-/-) mouse liver identifying the role of iPLA2γ in hepatic lipid second messenger production. Collectively, these results demonstrate the utility of high mass accuracy product ion analysis in conjunction with charge-switch derivatization for the highly specific quantitation of diminutive amounts of LA, AA, and DHA metabolites in biologic systems. Copyright © 2013 Elsevier Inc. All rights reserved.

  7. Generic HPLC platform for automated enzyme reaction monitoring: Advancing the assay toolbox for transaminases and other PLP-dependent enzymes.

    Börner, Tim; Grey, Carl; Adlercreutz, Patrick


    Methods for rapid and direct quantification of enzyme kinetics independent of the substrate stand in high demand for both fundamental research and bioprocess development. This study addresses the need for a generic method by developing an automated, standardizable HPLC platform monitoring reaction progress in near real-time. The method was applied to amine transaminase (ATA) catalyzed reactions intensifying process development for chiral amine synthesis. Autosampler-assisted pipetting facilitates integrated mixing and sampling under controlled temperature. Crude enzyme formulations in high and low substrate concentrations can be employed. Sequential, small (1 µL) sample injections and immediate detection after separation permits fast reaction monitoring with excellent sensitivity, accuracy and reproducibility. Due to its modular design, different chromatographic techniques, e.g. reverse phase and size exclusion chromatography (SEC) can be employed. A novel assay for pyridoxal 5'-phosphate-dependent enzymes is presented using SEC for direct monitoring of enzyme-bound and free reaction intermediates. Time-resolved changes of the different cofactor states, e.g. pyridoxal 5'-phosphate, pyridoxamine 5'-phosphate and the internal aldimine were traced in both half reactions. The combination of the automated HPLC platform with SEC offers a method for substrate-independent screening, which renders a missing piece in the assay and screening toolbox for ATAs and other PLP-dependent enzymes.

  8. Using NMR, SIP, and MS measurements for monitoring subsurface biogeochemical reactions at the Rifle IFRC site

    Rosier, C. L.; Keating, K.; Williams, K. H.; Robbins, M.; Ntarlagiannis, D.; Grunewald, E.; Walsh, D. O.


    The Rifle Integrated Field Research Challenge (IFRC) site is located on a former uranium ore-processing facility in Rifle, Colorado (USA). Although removal of tailings and contaminated surface materials was completed in 1996, residual uranium contamination of groundwater and subsurface sediments remains. Since 2002, research at the site has primarily focused on quantifying uranium mobility associated with stimulated and natural biogeochemical processes. Uranium mobility at the Rifle IFRC site is typically quantified through direct sampling of groundwater; however, direct sampling does not provide information about the solid phase material outside of the borehole and continuous measurements are not always possible due to multiple constraints. Geophysical methods have been suggested as a minimally invasive alternative approach for long term monitoring of biogeochemical reactions associated with uranium remediation. In this study, nuclear magnetic resonance (NMR), spectral induced polarization (SIP), and magnetic susceptibility (MS) are considered as potential geophysical methods for monitoring the biogeochemical reactions occurring at the Rifle IFRC site. Additionally, a pilot field study using an NMR borehole-logging tool was carried out at the Rifle IFRC site. These methods are sensitive to changes in the chemical and physical subsurface properties that occur as a result of bioremediation efforts; specifically, changes in the redox state and chemical form of iron, production of iron sulfide minerals, production of the magnetic mineral magnetite, and associated changes in the pore geometry. Laboratory experiments consisted of monitoring changes in the NMR, SIP and MS response of an acetate-amended columns packed with sediments from the Rifle IFRC site over the course of two months. The MS values remained relatively stable throughout the course of the experiment suggesting negligible production of magnetic phases (e.g. magnetite, pyrrhotite) as a result of enhanced

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

    Kind, J.; Thiele, C. M.


    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.

  10. Monitoring of Adverse Drug Reactions Associated with Antihypertensive Medicines at a University Teaching Hospital in New Delhi

    Fowad Khurshid


    Full Text Available Aim To monitor the adverse drug reactions (ADRs caused by antihypertensive medicines prescribed in a university teaching hospital.Methods:he present work was an open, non-comparative, observational study conducted on hypertensive patients attending the Medicine OPD of Majeedia Hospital, Jamia Hamdard, New Delhi, India by conducting patient interviews and recording the data on ADR monitoring form as recommended by Central Drugs Standard Control Organization (CDSCO, Government of India.Results:A total of 21 adverse drug reactions were observed in 192 hypertensive patients. Incidence of adverse drug reactions was found to be higher in patients more than 40 years in age, and females experienced more ADRs (n = 14, 7.29 % than males, 7 (3.64 %. Combination therapy was associated with more number of adverse drug reactions (66.7 % as against monotherapy (33.3 %. Calcium channel blockers were found to be the most frequently associated drugs with adverse drug reactions (n = 7, followed by diuretics (n = 5, and beta- blockers (n = 4. Among individual drugs, amlodipine was found to be the commonest drug associated with adverse drug reactions (n = 7, followed by torasemide (n = 3. Adverse drug reactions associated with central nervous system were found to be the most frequent (42.8 % followed by musculo-skeletal complaints (23.8 % and gastro-intestinal disorders (14.3 %. Conclusions:The present pharmacovigilance study represents the adverse drug reaction profile of the antihypertensive medicines prescribed in our university teaching hospital. The above findings would be useful for physicians in rational prescribing. Calcium channel blockers were found to be the most frequently associated drugs with adverse drug reactions.

  11. Real-time monitoring of mass-transport-related enzymatic reaction kinetics in a nanochannel-array reactor.

    Li, Su-Juan; Wang, Chen; Wu, Zeng-Qiang; Xu, Jing-Juan; Xia, Xing-Hua; Chen, Hong-Yuan


    To understand the fundamentals of enzymatic reactions confined in micro-/nanosystems, the construction of a small enzyme reactor coupled with an integrated real-time detection system for monitoring the kinetic information is a significant challenge. Nano-enzyme array reactors were fabricated by covalently linking enzymes to the inner channels of a porous anodic alumina (PAA) membrane. The mechanical stability of this nanodevice enables us to integrate an electrochemical detector for the real-time monitoring of the formation of the enzyme reaction product by sputtering a thin Pt film on one side of the PAA membrane. Because the enzymatic reaction is confined in a limited nanospace, the mass transport of the substrate would influence the reaction kinetics considerably. Therefore, the oxidation of glucose by dissolved oxygen catalyzed by immobilized glucose oxidase was used as a model to investigate the mass-transport-related enzymatic reaction kinetics in confined nanospaces. The activity and stability of the enzyme immobilized in the nanochannels was enhanced. In this nano-enzyme reactor, the enzymatic reaction was controlled by mass transport if the flux was low. With an increase in the flux (e.g., >50 microL min(-1)), the enzymatic reaction kinetics became the rate-determining step. This change resulted in the decrease in the conversion efficiency of the nano-enzyme reactor and the apparent Michaelis-Menten constant with an increase in substrate flux. This nanodevice integrated with an electrochemical detector could help to understand the fundamentals of enzymatic reactions confined in nanospaces and provide a platform for the design of highly efficient enzyme reactors. In addition, we believe that such nanodevices will find widespread applications in biosensing, drug screening, and biochemical synthesis.

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

    Fernández-Guerra, Paula; Birkler, Rune I D; Merinero, Begoña


    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 mitocho......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......, 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...


    Kunarti, Eko Sri


    Monitoring of hydrolysis and condensation polymerization reactions of tetramethylorthosilicate-organosiloxane have been carried out. Proton transfer from the excited state of 8-hydroxy-1,3,6-pyrenetrisulfonic acid trisodium salt (pyranine) to surrounding water molecules was used as a sensitive fluorescence method for following the kinetics of water consumption during the early stages of the sol-gel polymerisation process. Changes in water/silane ratio, type of organosiloxane, mol ratio of or...

  14. Real-time electrochemical monitoring of the polymerase chain reaction by mediated redox catalysis.

    Deféver, Thibaut; Druet, Michel; Rochelet-Dequaire, Murielle; Joannes, Martine; Grossiord, Céline; Limoges, Benoit; Marchal, Damien


    We described the proof-of-principle of a nonoptical real-time PCR that uses cyclic voltammetry for indirectly monitoring the amplified DNA product generated in the PCR reaction solution after each PCR cycle. To enable indirect measurement of the amplicon produced throughout PCR, we monitor electrochemically the progressive consumption (i.e., the decrease of concentration) of free electroactive deoxynucleoside triphosphates (dNTPs) used for DNA synthesis. This is accomplished by exploiting the fast catalytic oxidation of native deoxyguanosine triphosphate (dGTP) or its unnatural analogue 7-deaza-dGTP by the one-electron redox catalysts Ru(bpy)(3)(3+) (with bpy = 2,2'-bipyridine) or Os(bpy)(3)(3+) generated at an electrode. To demonstrate the feasibility of the method, a disposable array of eight miniaturized self-contained electrochemical cells (working volume of 50 microL) has been developed and implemented in a classical programmable thermal cycler and then tested with the PCR amplification of two illustrated examples of real-world biological target DNA sequences (i.e., a relatively long 2300-bp sequence from the bacterial genome of multidrug-resistant Achromobacter xylosoxidans and a shorter 283-bp target from the human cytomegalovirus). Although the method works with both mediator/base couples, the catalytic peak current responses recorded with the Ru(bpy)(3)(3+)/dGTP couple under real-time PCR conditions are significantly affected by a continuous current drift and interference with the background solvent discharge, thus leading to poorly reproducible data. Much more reproducible and reliable results are finally obtained with the Os(bpy)(3)(3+)/7-deaza-dGTP, a result that is attributed to the much lower anodic potential at which the catalytic oxidation of 7-deaza-dGTP by Os(bpy)(3)(3+) is detected. Under these conditions, an exponential decrease of the catalytic signal as a function of the number of PCR cycles is obtained, allowing definition of a cycle

  15. Journey to the $M_{\\rm BH} - \\sigma$ relation: the fate of low mass black holes in the Universe

    Volonteri, Marta


    In this paper, we explore the establishment and evolution of the empirical correlation between black hole mass and velocity dispersion with redshift. We track the growth and accretion history of massive black holes starting from high redshift using two seeding models:(i) Population III remnants, and (ii) massive seeds from direct gas collapse. Although the seeds do not initially satisfy the $M_{\\rm BH} - \\sigma$ relation, the correlation is established and maintained at all times if self-regulating accretion episodes are associated with major mergers. The massive end of the $M_{\\rm BH} - \\sigma$ relation is established early, and lower mass MBHs migrate over time. How MBHs migrate toward the relation, the slope and the scatter of the relation all depend critically on the seeding model as well as the adopted self-regulation prescription. We expect flux limited AGN surveys and LISA to select accreting and merging MBHs respectively that have already migrated onto the $\\msigma$ relation. This is a consequence of ...

  16. Key role of temperature monitoring in interpretation of microwave effect on transesterification and esterification reactions for biodiesel production.

    Mazubert, Alex; Taylor, Cameron; Aubin, Joelle; Poux, Martine


    Microwave effects have been quantified, comparing activation energies and pre-exponential factors to those obtained in a conventionally-heated reactor for biodiesel production from waste cooking oils via transesterification and esterification reactions. Several publications report an enhancement of biodiesel production using microwaves, however recent reviews highlight poor temperature measurements in microwave reactors give misleading reaction performances. Operating conditions have therefore been carefully chosen to investigate non-thermal microwave effects alone. Temperature is monitored by an optical fiber sensor, which is more accurate than infrared sensors. For the transesterification reaction, the activation energy is 37.1kJ/mol (20.1-54.2kJ/mol) in the microwave-heated reactor compared with 31.6kJ/mol (14.6-48.7kJ/mol) in the conventionally-heated reactor. For the esterification reaction, the activation energy is 45.4kJ/mol (31.8-58.9kJ/mol) for the microwave-heated reactor compared with 56.1kJ/mol (55.7-56.4kJ/mol) for conventionally-heated reactor. The results confirm the absence of non-thermal microwave effects for homogenous-catalyzed reactions.

  17. Monitoring of incidence, severity, and causality of adverse drug reactions in hospitalized patients with cardiovascular disease

    Sharminder Kaur


    Conclusion : Development of ADR in one of every five cardiac patient points toward a grave situation, but a higher incidence of Type A reactions in cardiology department means that these can be avoided.

  18. Selected Reaction Monitoring (SRM Analysis of Epidermal Growth Factor Receptor (EGFR in Formalin Fixed Tumor Tissue

    Hembrough Todd


    Full Text Available Abstract Background Analysis of key therapeutic targets such as epidermal growth factor receptor (EGFR in clinical tissue samples is typically done by immunohistochemistry (IHC and is only subjectively quantitative through a narrow dynamic range. The development of a standardized, highly-sensitive, linear, and quantitative assay for EGFR for use in patient tumor tissue carries high potential for identifying those patients most likely to benefit from EGFR-targeted therapies. Methods A mass spectrometry-based Selected Reaction Monitoring (SRM assay for the EGFR protein (EGFR-SRM was developed utilizing the Liquid Tissue®-SRM technology platform. Tissue culture cells (n = 4 were analyzed by enzyme-linked immunosorbent assay (ELISA to establish quantitative EGFR levels. Matching formalin fixed cultures were analyzed by the EGFR-SRM assay and benchmarked against immunoassay of the non-fixed cultured cells. Xenograft human tumor tissue (n = 10 of non-small cell lung cancer (NSCLC origin and NSCLC patient tumor tissue samples (n = 23 were microdissected and the EGFR-SRM assay performed on Liquid Tissue lysates prepared from microdissected tissue. Quantitative curves and linear regression curves for correlation between immunoassay and SRM methodology were developed in Excel. Results The assay was developed for quantitation of a single EGFR tryptic peptide for use in FFPE patient tissue with absolute specificity to uniquely distinguish EGFR from all other proteins including the receptor tyrosine kinases, IGF-1R, cMet, Her2, Her3, and Her4. The assay was analytically validated against a collection of tissue culture cell lines where SRM analysis of the formalin fixed cells accurately reflects EGFR protein levels in matching non-formalin fixed cultures as established by ELISA sandwich immunoassay (R2 = 0.9991. The SRM assay was applied to a collection of FFPE NSCLC xenograft tumors where SRM data range from 305amol/μg to 12,860amol/μg and


    AbstractThe mechanism of pulsed potential waveform for monitoring antibody¯antigen interactions at immunosensor interfaces is discussed. Some examples of antibody¯antigen interactions at quartz crystal microbalance and polymer-modified ...


    M.Yadollahi; H.Bouhendi; M.J.Zohuriaan-Mehr; K.Kabiri


    This paper deals with the monitoring cyclo-addition of CO2 to methyl methacrylate (MMA)-glycidyl methacrylate (GMA) copolymers using spectral (1H-NMR and FTIR) and chemical (elemental analysis and titration) methods.Thus,poly(MMA-co-GMA),was first prepared via solution polymerization.The copolymer was then treated with CO2 gas flow in the presence of cetyltrimethyl ammoniumbromide as a catalyst.In terms of the carbonation reaction time,the terpolymer poly(MMA-co-GMA-co-2-oxo-l,3-dioxolane-4-yl-methyl methacrylate) was prepared in various yield of CO2 fixation (> 90%).The peak intensity changes in the 1H-NMR and FTIR spectra provided excellent demonstrative techniques to monitor the carbonation reaction progression.In a comparative analytical viewpoint,the NMR and elemental analysis were recognized to be the most accurate ways to follow the cyclo-addition reaction progression.However,titration was recognized to be the most preferred method,because it is a very inexpensive,facile and available method with a reasonable costaccuracy balance.

  1. Micro flow reactor chips with integrated luminescent chemosensors for spatially resolved on-line chemical reaction monitoring.

    Gitlin, Leonid; Hoera, Christian; Meier, Robert J; Nagl, Stefan; Belder, Detlev


    Real-time chemical reaction monitoring in microfluidic environments is demonstrated using luminescent chemical sensors integrated in PDMS/glass-based microscale reactors. A fabrication procedure is presented that allows for straightforward integration of thin polymer layers with optical sensing functionality in microchannels of glass-PDMS chips of only 150 μm width and of 10 to 35 μm height. Sensor layers consisting of polystyrene and an oxygen-sensitive platinum porphyrin probe with film thicknesses of about 0.5 to 4 μm were generated by combining spin coating and abrasion techniques. Optimal coating procedures were developed and evaluated. The chip-integrated sensor layers were calibrated and investigated with respect to stability, reproducibility and response times. These microchips allowed observation of dissolved oxygen concentration in the range of 0 to over 40 mg L(-1) with a detection limit of 368 μg L(-1). The sensor layers were then used for observation of a model reaction, the oxidation of sulphite to sulphate in a microfluidic chemical reactor and could observe sulphite concentrations of less than 200 μM. Real-time on-line monitoring of this chemical reaction was realized at a fluorescence microscope setup with 405 nm LED excitation and CCD camera detection.

  2. Determination of molecular weight and other characteristics of co- and terpolymers using automatic continuous online monitoring of polymerization reactions (ACOMP)

    Enohnyaket, Pascal E. A.

    The Automatic Continuous Online Monitoring of Polymerization reactions (ACOMP), is a technique developed by the Reed Research Group at Tulane University. By simultaneously monitoring and combining signals from a continuously dilute reactor stream, detectors such as a multi-angle light scattering detector, near infra-red spectrometer, viscometer, differential refractive index, and a full wavelength UV/Visible detector were used in a model-independent fashion to follow the weight-average molecular weight, intrinsic viscosity, the concentrations of each comonomer, and hence the evolution of the average instantaneous and cumulative compositions along the chains as comonomers are consumed. The goal of this dissertation is to make the ACOMP system more useful in very complex polymerization situations by improving it with additional detectors and formalisms (such as a new expression for computing the molecular weight a copolymer of nth degree) and to exploit its robustness in situations where traditional routes fail or are of limited value. By providing a continuum of data, ACOMP allows polymer scientists to better understand and control new reaction schemes. At the pilot plant, it can be used to optimize reaction conditions. Because the ACOMP system is relatively cheap, user friendly, can be environmentally friendly, less bulky and very efficient, it is my desire to use ACOMP to solve some of the problems in the petroleum, plastic and drug manufacturing industries in Cameroon (and Africa).

  3. Real-time monitoring of viscosity changes triggered by chemical reactions using a high-speed imaging method

    Wooseok Jung


    Full Text Available We present a method to monitor in real time peptide self-assembly or polymerization events. The temperature controlled modification of a previously reported splash test setup using high speed imaging enables to observe and measure rheological changes in liquid samples and can, in turn, monitor a peptide self-assembly or polymerization reaction accompanied with specific changes in solution viscosity. A series of 2 mm glass beads were dropped into an Fmoc-L3-OMe (methylated Fluorenylmethyloxycarbonyl-trileucine solution mixed with Alcalase 2.4 L (EC or first dipped in Tetramethylethylenediamine (TEMED, a catalyst for acrylamide polymerization, then dropped into acrylamide. The resulting splashes were observed using a high speed camera. The results demonstrate that the viscosity changes of the peptide sample during the peptide self-assembly or acrylamide polymerization affect the specific shape and evolution of the splashing event. Typically, the increase in viscosity while the reaction occurs decreased the size of the splash and the amount of time for the splash to reach maximum extension from the moment for the beads to impact the sample. The ability to observe rheological changes of sample state presents the opportunity to monitor the real time dynamics of peptide self-assembly or cross-polymerization.

  4. Raman spectroscopy as a tool for monitoring mesoscale continuous-flow organic synthesis: Equipment interface and assessment in four medicinally-relevant reactions

    Trevor A. Hamlin


    Full Text Available An apparatus is reported for real-time Raman monitoring of reactions performed using continuous-flow processing. Its capability is assessed by studying four reactions, all involving formation of products bearing α,β-unsaturated carbonyl moieties; synthesis of 3-acetylcoumarin, Knoevenagel and Claisen–Schmidt condensations, and a Biginelli reaction. In each case it is possible to monitor the reactions and also in one case, by means of a calibration curve, determine product conversion from Raman spectral data as corroborated by data obtained using NMR spectroscopy.

  5. Using an infrared probe for in situ monitoring of esterifying reactions

    Francisco José Sánchez Castellanos


    Full Text Available A batch reactor was employed having pH meter, IR probe and continuous operation detectors so that it could work as a CSTR reactor. As esterification advanced, then IR bands corresponding to the carboxyl acid COOH group and the alcohol C-OH group decreased whilst a parallel increase was presented in the ester -COOR group band which was forming. Reaction progress could be observed by continuous IR spectrum registration. The IR band for HOH (water could not be studied because it needed a completely anhydrous medium for doing so. Standard solutions could be prepared for quantifying IR band peak intensity, according to a component’s composition in the mixture. However, when phase changes occurred in the reaction mixture, this method could not be employed for following the course of a particular reaction because random variation was detected in band intensity.

  6. Straightforward method to quantify GSH, GSSG, GRP, and hydroxycinnamic acids in wines by UPLC-MRM-MS.

    Vallverdú-Queralt, Anna; Verbaere, Arnaud; Meudec, Emmanuelle; Cheynier, Veronique; Sommerer, Nicolas


    A novel, robust and fast ultrahigh performance liquid chromatography–multiple reaction monitoring mass spectrometry method has been developed for the simultaneous quantification of reduced glutathione (GSH), oxidized glutathione (GSSG), grape reaction product (GRP) and hydroxycinnamic acids in wine. The method was evaluated in terms of linearity, precision, accuracy, limits of detection and quantification, stability and matrix effects. Quantitative recovery (74–110%) and satisfactory interday precision (RSD wine samples with different levels of oxidation were analyzed. Levels of GSH and GSSG varied from 1.63 to 9.91 mg/L and from 0.32 to 3.33 mg/L, respectively. Levels of caftaric acid ranged from 2.57 to 293.07 mg/L. Levels of GRP were between 28.35 and 114.20 mg/L.

  7. Postmarketing surveillance of adverse drug reactions in general practice. II: Prescription-event monitoring at the University of Southampton.

    Inman, W H


    An independent, non-regulatory drug surveillance research unit has been established at the University of Southampton. Its first task will be to set up a prescription-event monitoring scheme in general practice to enable the pattern of adverse events, as distinct from suspected adverse reactions associated with new drugs to be compared with that of older medicines. Prescriptions for selected drugs will identify patients and a simple questionnaire, designed to be completed in under five minutes, will be used to obtain the required information. Medical opinions about causation need not be given, and the scheme will not interfere with normal prescribing practice.

  8. IAEA coordinated research project on nuclear data for charged-particle monitor reactions and medical isotope production

    Capote, Roberto; Nichols, Alan L.; Nortier, Francois Meiring; Carlson, Brett V.; Engle, Jonathan W.; Hermanne, Alex; Hussain, Mazhar; Ignatyuk, Anatoly V.; Kellett, Mark A.; Kibédi, Tibor; Kim, Guinyun; Kondev, Filip G.; Lebeda, Ondrej; Luca, Aurelian; Naik, Haladhara; Nagai, Yasuki; Spahn, Ingo; Suryanarayana, Saraswatula V.; Tárkányi, Ferenc T.; Verpelli, Marco


    An IAEA coordinated research project was launched in December 2012 to establish and improve the nuclear data required to characterise charged-particle monitor reactions and extend data for medical radionuclide production. An international team was assembled to undertake work addressing the requirements for more accurate cross-section data over a wide range of targets and projectiles, undertaken in conjunction with a limited number of measurements and more extensive evaluations of the decay data of specific radionuclides. These studies are nearing completion, and are briefly described below.

  9. Radioactive phosphorylation of alcohols to monitor biocatalytic Diels-Alder reactions.

    Alexander Nierth

    Full Text Available Nature has efficiently adopted phosphorylation for numerous biological key processes, spanning from cell signaling to energy storage and transmission. For the bioorganic chemist the number of possible ways to attach a single phosphate for radioactive labeling is surprisingly small. Here we describe a very simple and fast one-pot synthesis to phosphorylate an alcohol with phosphoric acid using trichloroacetonitrile as activating agent. Using this procedure, we efficiently attached the radioactive phosphorus isotope (32P to an anthracene diene, which is a substrate for the Diels-Alderase ribozyme-an RNA sequence that catalyzes the eponymous reaction. We used the (32P-substrate for the measurement of RNA-catalyzed reaction kinetics of several dye-labeled ribozyme variants for which precise optical activity determination (UV/vis, fluorescence failed due to interference of the attached dyes. The reaction kinetics were analyzed by thin-layer chromatographic separation of the (32P-labeled reaction components and densitometric analysis of the substrate and product radioactivities, thereby allowing iterative optimization of the dye positions for future single-molecule studies. The phosphorylation strategy with trichloroacetonitrile may be applicable for labeling numerous other compounds that contain alcoholic hydroxyl groups.

  10. Monitoring of reinforced concrete structures affected by alkali-silica reaction

    Siemes, A.J.M.; Gulikers, J.J.W.


    Recent inspections of 20 bridges in a highway in The Netherlands revealed that ASR had affected the concrete. Until then alkali-silica reaction (ASR) was a rather rare phenomenon. In view of the expected, future importance of the maintenance of Dutch infrastructure, it was decided to start a

  11. Manipulating and Monitoring On-Surface Biological Reactions by Light-Triggered Local pH Alterations.

    Peretz-Soroka, Hagit; Pevzner, Alexander; Davidi, Guy; Naddaka, Vladimir; Kwiat, Moria; Huppert, Dan; Patolsky, Fernando


    Significant research efforts have been dedicated to the integration of biological species with electronic elements to yield smart bioelectronic devices. The integration of DNA, proteins, and whole living cells and tissues with electronic devices has been developed into numerous intriguing applications. In particular, the quantitative detection of biological species and monitoring of biological processes are both critical to numerous areas of medical and life sciences. Nevertheless, most current approaches merely focus on the "monitoring" of chemical processes taking place on the sensing surfaces, and little efforts have been invested in the conception of sensitive devices that can simultaneously "control" and "monitor" chemical and biological reactions by the application of on-surface reversible stimuli. Here, we demonstrate the light-controlled fine modulation of surface pH by the use of photoactive molecularly modified nanomaterials. Through the use of nanowire-based FET devices, we showed the capability of modulating the on-surface pH, by intensity-controlled light stimulus. This allowed us simultaneously and locally to control and monitor pH-sensitive biological reactions on the nanodevices surfaces, such as the local activation and inhibition of proteolytic enzymatic processes, as well as dissociation of antigen-antibody binding interactions. The demonstrated capability of locally modulating the on-surface effective pH, by a light stimuli, may be further applied in the local control of on-surface DNA hybridization/dehybridization processes, activation or inhibition of living cells processes, local switching of cellular function, local photoactivation of neuronal networks with single cell resolution and so forth.

  12. Benzoin Condensation: Monitoring a Chemical Reaction by High-Pressure Liquid Chromatography

    Bhattacharya, Apurba; Purohit, Vikram C.; Bellar, Nicholas R.


    High-pressure liquid chromatography (HPLC) is the preferred method of separating a variety of materials in complex mixtures such as pharmaceuticals, polymers, soils, food products and biological fluids and is also considered to be a powerful analytical tool in both academia and industry. The use of HPLC analysis as a means of monitoring and…

  13. Reaction monitoring using hyperpolarized NMR with scaling of heteronuclear couplings by optimal tracking

    Zhang, Guannan; Schilling, Franz; Glaser, Steffen J.; Hilty, Christian


    Off-resonance decoupling using the method of Scaling of Heteronuclear Couplings by Optimal Tracking (SHOT) enables determination of heteronuclear correlations of chemical shifts in single scan NMR spectra. Through modulation of J-coupling evolution by shaped radio frequency pulses, off resonance decoupling using SHOT pulses causes a user-defined dependence of the observed J-splitting, such as the splitting of 13C peaks, on the chemical shift offset of coupled nuclei, such as 1H. Because a decoupling experiment requires only a single scan, this method is suitable for characterizing on-going chemical reactions using hyperpolarization by dissolution dynamic nuclear polarization (D-DNP). We demonstrate the calculation of [13C, 1H] chemical shift correlations of the carbanionic active sites from hyperpolarized styrene polymerized using sodium naphthalene as an initiator. While off resonance decoupling by SHOT pulses does not enhance the resolution in the same way as a 2D NMR spectrum would, the ability to obtain the correlations in single scans makes this method ideal for determination of chemical shifts in on-going reactions on the second time scale. In addition, we present a novel SHOT pulse that allows to scale J-splittings 50% larger than the respective J-coupling constant. This feature can be used to enhance the resolution of the indirectly detected chemical shift and reduce peak overlap, as demonstrated in a model reaction between p-anisaldehyde and isobutylamine. For both pulses, the accuracy is evaluated under changing signal-to-noise ratios (SNR) of the peaks from reactants and reaction products, with an overall standard deviation of chemical shift differences compared to reference spectra of 0.02 ppm when measured on a 400 MHz NMR spectrometer. Notably, the appearance of decoupling side-bands, which scale with peak intensity, appears to be of secondary importance.

  14. Real-time monitoring of the setting reaction of brushite-forming cement using isothermal differential scanning calorimetry.

    Hofmann, M P; Nazhat, S N; Gbureck, U; Barralet, J E


    The setting behavior of a brushite-forming cement (beta-tricalcium phosphate/mono calcium monophosphate) was investigated using an indentation technique (the Gillmore needles method) and isothermal differential scanning calorimetry (DSC). The two objectives of the study were to investigate whether DSC could be used to real-time monitor a fast-setting calcium phosphate cement (CPC) and to determine if it is possible to correlate DSC results directly with conventional setting-time measurements. Best-fit linear correlation analysis revealed that both the initial and final setting time (T(i) and T(f)) measured by indentation were strongly correlated to the maximum heat flow measured with DSC. It seems therefore possible to predict the setting times, usually achieved with user dependent indentation methods, of this specific fast setting CPC on the basis of objective DSC measurements. The drawbacks of DSC, however, are its overall complexity and expense and the fact that only exothermal reactions can be investigated in comparison to the Gillmore needles method, furthermore, it is not possible to monitor the complete reaction as the first 2 or 3 min are lost due to sample preparation and apparatus set up.

  15. Process spectroscopy in microemulsions—setup and multi-spectral approach for reaction monitoring of a homogeneous hydroformylation process

    Meyer, K.; Ruiken, J.-P.; Illner, M.; Paul, A.; Müller, D.; Esche, E.; Wozny, G.; Maiwald, M.


    Reaction monitoring in disperse systems, such as emulsions, is of significant technical importance in various disciplines like biotechnological engineering, chemical industry, food science, and a growing number other technical fields. These systems pose several challenges when it comes to process analytics, such as heterogeneity of mixtures, changes in optical behavior, and low optical activity. Concerning this, online nuclear magnetic resonance (NMR) spectroscopy is a powerful technique for process monitoring in complex reaction mixtures due to its unique direct comparison abilities, while at the same time being non-invasive and independent of optical properties of the sample. In this study the applicability of online-spectroscopic methods on the homogeneously catalyzed hydroformylation system of 1-dodecene to tridecanal is investigated, which is operated in a mini-plant scale at Technische Universität Berlin. The design of a laboratory setup for process-like calibration experiments is presented, including a 500 MHz online NMR spectrometer, a benchtop NMR device with 43 MHz proton frequency as well as two Raman probes and a flow cell assembly for an ultraviolet and visible light (UV/VIS) spectrometer. Results of high-resolution online NMR spectroscopy are shown and technical as well as process-specific problems observed during the measurements are discussed.

  16. Sensitive electrochemical monitoring of nucleic acids coupling DNA nanostructures with hybridization chain reaction

    Zhuang, Junyang; Fu, Libing; Xu, Mingdi; Yang, Huanghao; Chen, Guonan; Tang, Dianping, E-mail:


    Graphical abstract: -- Highlights: •A new signal-on metallobioassay was developed for detection of nucleic acids. •Target-triggered long-range self-assembled DNA nanostructures are used for amplification of electronic signal. •Hybridization chain reaction is utilized for construction of long-range DNA nanostructures. -- Abstract: Methods based on metal nanotags have been developed for metallobioassay of nucleic acids, but most involve complicated labeling or stripping procedures and are unsuitable for routine use. Herein, we report the proof-of-concept of a novel and label-free metallobioassay for ultrasensitive electronic determination of human immunodeficiency virus (HIV)-related gene fragments at an ultralow concentration based on target-triggered long-range self-assembled DNA nanostructures and DNA-based hybridization chain reaction (HCR). The signal is amplified by silver nanotags on the DNA duplex. The assay mainly consists of capture probe, detection probe, and two different DNA hairpins. In the presence of target DNA, the capture probe immobilized on the sensor sandwiches target DNA with the 3′ end of detection probe. Another exposed part of detection probe at the 5′ end opens two alternating DNA hairpins in turn, and propagates a chain reaction of hybridization events to form a nicked double-helix. Finally, numerous silver nanotags are immobilized onto the long-range DNA nanostructures, each of which produces a strong electronic signal within the applied potentials. Under optimal conditions, the target-triggered long-range DNA nanostructures present good electrochemical behaviors for the detection of HIV DNA at a concentration as low as 0.5 fM. Importantly, the outstanding sensitivity can make this approach a promising scheme for development of next-generation DNA sensors without the need of enzyme labeling or fluorophore labeling.

  17. Monitoring the wild black bear's reaction to human and environmental stressors

    Iaizzo Paul A


    Full Text Available Abstract Background Bears are among the most physiologically remarkable mammals. They spend half their life in an active state and the other half in a state of dormancy without food or water, and without urinating, defecating, or physical activity, yet can rouse and defend themselves when disturbed. Although important data have been obtained in both captive and wild bears, long-term physiological monitoring of bears has not been possible until the recent advancement of implantable devices. Results Insertable cardiac monitors that were developed for use in human heart patients (Reveal® XT, Medtronic, Inc were implanted in 15 hibernating bears. Data were recovered from 8, including 2 that were legally shot by hunters. Devices recorded low heart rates (pauses of over 14 seconds and low respiration rates (1.5 breaths/min during hibernation, dramatic respiratory sinus arrhythmias in the fall and winter months, and elevated heart rates in summer (up to 214 beats/min (bpm and during interactions with hunters (exceeding 250 bpm. The devices documented the first and last day of denning, a period of quiescence in two parturient females after birthing, and extraordinary variation in the amount of activity/day, ranging from 0 (winter to 1084 minutes (summer. Data showed a transition toward greater nocturnal activity in the fall, preceding hibernation. The data-loggers also provided evidence of the physiological and behavioral responses of bears to our den visits to retrieve the data. Conclusions Annual variations in heart rate and activity have been documented for the first time in wild black bears. This technique has broad applications to wildlife management and physiological research, enabling the impact of environmental stressors from humans, changing seasons, climate change, social interactions and predation to be directly monitored over multiple years.

  18. Monitoring Wnt Protein Acylation Using an In Vitro Cyclo-Addition Reaction

    Tuladhar, Rubina; Yarravarapu, Nageswari; Lum, Lawrence


    We describe here a technique for visualizing the lipidation status of Wnt proteins using azide-alkyne cycloaddition chemistry (click chemistry) and SDS-PAGE. This protocol incorporates in vivo labeling of a Wnt-IgG Fc fusion protein using an alkynylated palmitate probe but departs from a traditional approach by incorporating a secondary cycloaddition reaction performed on single-step purified Wnt protein immobilized on protein A resin. This approach mitigates experimental noise by decreasing the contribution of labeling from other palmitoylated proteins and by providing a robust method for normalizing labeling efficiency based on protein abundance. PMID:27590147

  19. In-Situ Cure Monitoring of the Immidization Reaction of PMR-15

    Cossins, Sheryl; Kellar, Jon J.; Winter, Robb M.


    Glass fiber reinforced polymer composites are becoming widely used in industry. With this increase in production, an in-situ method of quality control for the curing of the polymer is desirable. This would allow for the production of high-quality parts having more uniform properties.' Recently, in-situ fiber optic monitoring of polymer curing has primarily focused on epoxy resins and has been performed by Raman or fluorescence methods. In addition, some infrared (IR) investigations have been performed using transmission or ATR cells. An alternate IR approach involves using optical fibers as a sensor by utilizing evanescent wave spectroscopy.

  20. Video and thermal imaging system for monitoring interiors of high temperature reaction vessels

    Saveliev, Alexei V [Chicago, IL; Zelepouga, Serguei A [Hoffman Estates, IL; Rue, David M [Chicago, IL


    A system and method for real-time monitoring of the interior of a combustor or gasifier wherein light emitted by the interior surface of a refractory wall of the combustor or gasifier is collected using an imaging fiber optic bundle having a light receiving end and a light output end. Color information in the light is captured with primary color (RGB) filters or complimentary color (GMCY) filters placed over individual pixels of color sensors disposed within a digital color camera in a BAYER mosaic layout, producing RGB signal outputs or GMCY signal outputs. The signal outputs are processed using intensity ratios of the primary color filters or the complimentary color filters, producing video images and/or thermal images of the interior of the combustor or gasifier.


    N. A. Onishchenko


    Full Text Available In this review article the necessity of adaptation and introduction into clinical practice of simultaneous monitoring of immune blood cells and cytokines in patients with grafted organs for a choice of individual tactic of immuno- suppressive therapy, determination of its efficiency and forecasting is proved. It is emphasized, that with the spe- cial attention it ought to concern to characteristic of CD4 + T-lymphocytes and to definition of an interrelation of their separate populations in peripheral blood (Treg, Th17, Tact memory cells – CD4+CD25hiCD127hiCD45RO since they are the basic participants of immune system reaction on grafts. 

  2. Enantioselective reaction monitoring utilizing two-dimensional heart-cut liquid chromatography on an integrated microfluidic chip.

    Lotter, Carsten; Poehler, Elisabeth; Heiland, Josef J; Mauritz, Laura; Belder, Detlev


    Chip-integrated, two-dimensional high performance liquid chromatography is introduced to monitor enantioselective continuous micro-flow synthesis. The herein described development of the first two-dimensional HPLC-chip was realized by the integration of two different columns packed with reversed-phase and chiral stationary phase material on a microfluidic glass chip, coupled to mass spectrometry. Directed steering of the micro-flows at the joining transfer cross enabled a heart-cut operation mode to transfer the chiral compound of interest from the first to the second chromatographic dimension. This allows for an interference-free determination of the enantiomeric excess by seamless hyphenation to electrospray mass spectrometry. The application for rapid reaction optimization at micro-flow conditions is exemplarily shown for the asymmetric organocatalytic continuous micro-flow synthesis of warfarin.

  3. Detection of Legionella by quantitative-polymerase chain reaction (qPCR) for monitoring and risk assessment

    Krøjgaard, Louise H.; Krogfelt, Karen A.; Albrechtsen, Hans-Jorgen


    Background: Culture and quantitative polymerase chain reaction (qPCR) assays for the detection of Legionella were compared on samples from a residential area before and after two interventions. A total of 84 samples were collected from shower hoses and taps as first flush samples and at constant...... temperature. Samples were grouped according to the origin of the sample, a) circulation water b) water from empty apartments c) water from shower hoses. The aims were to investigate the usefulness of qPCR compared to culture for monitoring remedial actions for elimination of Legionella bacteria and as a tool...... for risk assessment. Results: In water collected from the apartments Legionella spp were detected by qPCR in the concentration range from LOQ to 9.6* 10(5)GU/L while L. pneumophila were detected in a range from LOQ to 6.8*10(5) GU/L. By culturing, the legionellae were detected in the range from below...

  4. Infrared Thermography-based Biophotonics: Integrated Diagnostic Technique for Systemic Reaction Monitoring

    Vainer, Boris G.; Morozov, Vitaly V.

    A peculiar branch of biophotonics is a measurement, visualisation and quantitative analysis of infrared (IR) radiation emitted from living object surfaces. Focal plane array (FPA)-based IR cameras make it possible to realize in medicine the so called interventional infrared thermal diagnostics. An integrated technique aimed at the advancement of this new approach in biomedical science and practice is described in the paper. The assembled system includes a high-performance short-wave (2.45-3.05 μm) or long-wave (8-14 μm) IR camera, two laser Doppler flowmeters (LDF) and additional equipment and complementary facilities implementing the monitoring of human cardiovascular status. All these means operate synchronously. It is first ascertained the relationship between infrared thermography (IRT) and LDF data in humans in regard to their systemic cardiovascular reactivity. Blood supply real-time dynamics in a narcotized patient is first visualized and quantitatively represented during surgery in order to observe how the general hyperoxia influences thermoregulatory mechanisms; an abrupt increase in temperature of the upper limb is observed using IRT. It is outlined that the IRT-based integrated technique may act as a take-off runway leading to elaboration of informative new methods directly applicable to medicine and biomedical sciences.

  5. In situ monitoring of brain tissue reaction of chronically implanted electrodes with an optical coherence tomography fiber system

    Xie, Yijing; Hassler, Christina; Stieglitz, Thomas; Seifert, Andreas; Hofmann, Ulrich G.


    Neural microelectrodes are well established tools for delivering therapeutic electrical pulses, and recording neural electrophysiological signals. However, long term implanted neural probes often become functionally impaired by tissue encapsulation. At present, analyzing this immune reaction is only feasible with post-mortem histology; currently no means for specific in vivo monitoring exist and most applicable imaging modalities provide no sufficient resolution for a cellular measurement in deep brain regions. Optical coherence tomography (OCT) is a well developed imaging modality, providing cellular resolution and up to 1.2 mm imaging depth in brain tissue. Further more, a fiber based spectral domain OCT was shown to be capable of minimally invasive brain intervention. In the present study, we propose to use a fiber based spectral domain OCT to monitor the the progression of the tissue's immune response and scar encapsulation of microprobes in a rat animal model. We developed an integrated OCT fiber catheter consisting of an implantable ferrule based fiber cannula and a fiber patch cable. The fiber cannula was 18.5 mm long, including a 10.5 mm ceramic ferrule and a 8.0 mm long, 125 μm single mode fiber. A mating sleeve was used to fix and connect the fiber cannula to the OCT fiber cable. Light attenuation between the OCT fiber cable and the fiber cannula through the mating sleeve was measured and minimized. The fiber cannula was implanted in rat brain together with a microelectrode in sight used as a foreign body to induce the brain tissue immune reaction. Preliminary data showed a significant enhancement of the OCT backscattering signal during the brain tissue scarring process, while the OCT signal of the flexible microelectrode was getting weaker consequentially.

  6. Improvement of estradiol esters monitoring in bovine hair by dansylation and liquid chromatography/tandem mass spectrometry analysis in multiple reaction monitoring and precursor ion scan modes.

    Bichon, E; Béasse, A; Prevost, S; Christien, S; Courant, F; Monteau, F; Le Bizec, B


    The control of forbidden anabolic practices in cattle in the European Union has become challenging since endogenous compounds such as estradiol derivatives can potentially be used as growth promoters. Due to the great difficulty in establishing a reference threshold value for endogenous steroids, the direct detection of steroid esters in hair is an efficient strategy for the detection of 'natural' steroid abuse in cattle. The present study aimed to develop and validate according to the current European standards a specific liquid chromatography/tandem mass spectrometry (LC/MS/MS) analytical strategy to monitor estrogen esters in bovine hair. The analysis was performed by positive ion electrospray ionisation (ESI+) after dansylation. Two acquisition modes were then assessed: single reaction monitoring and precursor ion scanning. The results showed that the introduction of a dansylation step strongly improves the sensitivity of the detection of estradiol-17-esters by LC/(ESI+)-MS/MS. The CCα values are in the range 1-10 ng g(-1) after optimisation, except for estradiol decanoate for which the derivatisation is not efficient. In addition, this LC/MS/MS approach makes it possible to carry out a precursor ion scan to screen for the presence of these estradiol 17-esters in hair samples. Based on the specific product ions, i.e. m/z 255 in native conditions or m/z 171 after dansylation, this strategy has the advantage of detecting any (un)known estradiol ester and of giving access to the [M + H](+) ion of the suspected ester through only a single analysis. Copyright © 2012 John Wiley & Sons, Ltd.

  7. The electronic behavior of a photosynthetic reaction center monitored by conductive atomic force microscopy.

    Mikayama, Takeshi; Iida, Kouji; Suemori, Yoshiharu; Dewa, Takehisa; Miyashita, Tokuji; Nango, Mamoru; Gardiner, Alastair T; Cogdell, Richard J


    The conductivity of a photosynthetic reaction center (RC) from Rhodobacter sphaeroides was measured with conductive atomic force microscopy (CAFM) on SAM-modified Au(111) substrates. 2-mercaptoethanol (2ME), 2-mercaptoacetic acid (MAC), 2-mercaptopyridine (2MP) and 4-mercaptopyridine (4MP) were prepared as SAM materials to investigate the stability and morphology of RCs on the substrate by using near-IR absorption spectroscopy and AFM, respectively. The clear presence of the three well known RC near-IR absorption peaks indicates that the RCs were native on the SAM-modified Au(111). Dense grains with various diameters of 5-20 nm, which corresponded to mixtures of single RCs up to aggregates of 10, were observed in topographs of RCs adsorbed on all the different SAM-modified Au(111) substrates. The size of currents obtained from the RC using a bare conductive cantilever were produced in the following order for SAM molecules: 2MP > 2ME > 4MP > MAC. A clear rectification of this current was observed for the modification of the Au(111) substrate with the pi-conjugated thiol, 2MP, indicating that 2MP was effective in both promoting the specific orientation of the RCs on the electrode and electron injection into the RC. Cyclic voltammetry measurements indicate that the 2MP is better mediator for the electron transfer between a quinone and substrate. The current with 2MP-modified cantilever was twice as high as that obtained with the Au-coated one alone, indicating that 2MP has an important role in lowering the electron injection barrier between special pair side of RC and gold electrode.

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

    Lori K Van Ness

    Full Text Available 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.

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

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


    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.

  10. Continuous monitoring of the zinc-phosphate acid-base cement setting reaction by proton nuclear magnetic relaxation

    Apih, T.; Lebar, A.; Pawlig, O.; Trettin, R.


    Proton nuclear magnetic relaxation is a well-established technique for continuous and non destructive monitoring of hydration of conventional Portland building cements. Here, we demonstrate the feasibility of nuclear magnetic resonance (NMR) monitoring of the setting reaction of zinc-phosphate acid-base dental cements, which harden in minutes as compared to days, as in the case of Portland cements. We compare the setting of cement powder (mainly, zinc oxide) prepared with clinically used aluminum-modified orthophosphoric acid solution with the setting of a model system where cement powder is mixed with pure orthophosphoric acid solution. In contrast to previously published NMR studies of setting Portland cements, where a decrease of spin-lattice relaxation time is attributed to enhanced relaxation at the growing internal surface, spin-lattice relaxation time T1 increases during the set of clinically used zinc-phosphate cement. Comparison of these results with a detailed study of diffusion, viscosity, and magnetic-field dispersion of T1 in pure and aluminum-modified orthophosphoric acid demonstrates that the increase of T1 in the setting cement is connected with the increase of molecular mobility in the residual phosphoric acid solution. Although not taken into account so far, such effects may also significantly influence the relaxation times in setting Portland cements, particularly when admixtures with an effect on water viscosity are used.

  11. Quantitative label-free and real-time surface-enhanced Raman scattering monitoring of reaction kinetics using self-assembled bifunctional nanoparticle arrays.

    Zhang, Kun; Zhao, Jingjing; Ji, Ji; Li, Yixin; Liu, Baohong


    Although surface-enhanced Raman scattering (SERS) has proven to be an effective tool for label-free monitoring of catalytic reactions, quantitative characterization of reaction kinetics via this technique remains challenging owing to the difficulty in integrating catalytic and plasmonic activities into a single platform. In this work, we report on an easy access to highly sensitive plasmonic nanoarrays for direct and label-free monitoring of a gold-catalyzed reaction by SERS. The hierarchically structured three-dimensional assemblies, which consist of small gold catalyst nanoparticles distributed on a self-assembled monolayer of larger gold nanoparticles, were formed through a simple and rapid stepwise interfacial self-assembling process (fabrication time quantitative determination of the rate constant and activation energy of the catalytic reaction with SERS.

  12. Infrared tunable diode laser applications: (i) atmospheric pollutants monitoring (ii) gas phase kinetics of elementary reactions; Application des diodes laser infrarouge accordables a deux problematiques: (i) la metrologie de polluants (ii) la cinetique des reactions elementaires

    Dusanter, S.


    Infrared Tunable Diode Laser Absorption Spectroscopy provides sensibility, selectivity and high temporal resolution. We have applied this technique to atmospheric trace pollutants monitoring and to gas phase kinetics of elementary reactions. For metrology, we have developed a novel and effective protocol: pressure increase measurements. It has been applied to monitoring nitrous oxide, formaldehyde, acetaldehyde and 1,3-butadiene, in air or car exhausts. This work represents a first step toward the elaboration of a compact and portable instrument. The kinetic setup, where reactions are initiated by laser photolysis, has been validated with the well-known reactions of formyl and hydroxymethyl radicals with oxygen. A preliminary study of the rate constant for the unimolecular decomposition of pivaloyl radical has been performed. (author)

  13. Optical fiber chemical sensors with sol-gel derived nanomaterials for monitoring high temperature/high pressure reactions in clean energy technologies

    Tao, Shiquan


    The development of sensor technologies for in situ, real time monitoring the high temperature/high pressure (HTP) chemical processes used in clean energy technologies is a tough challenge, due to the HTP, high dust and corrosive chemical environment of the reaction systems. A silica optical fiber is corrosive resistance, and can work in HTP conditions. This paper presents our effort in developing fiber optic sensors for in situ, real time monitoring the concentration of trace ammonia and hydrogen in high temperature gas samples. Preliminary test results illustrate the feasibility of using fiber optic sensor technologies for monitoring HTP processes for next generation energy industry.

  14. Quantification of matrix metalloprotease-9 in bronchoalveolar lavage fluid by selected reaction monitoring with microfluidics nano-liquid-chromatography-mass spectrometry

    Prely, Laurette M.; Paal, Krisztina; Hermans, Jos; van der Heide, Sicco; van Oosterhout, Antoon J. M.; Bischoff, Rainer


    Quantitative protein analysis by liquid chromatography-tandem mass spectrometry (LC-MS/MS) in the selected reaction monitoring (SRM) mode was used to quantify matrix metalloprotease-9 (MMP-9; similar to 90 kDa) in bronchoalveolar lavage fluid (BALF) from patients having undergone lung transplantatio

  15. Use of a high resolution melt real-time polymerase chain reaction (PCR) assay for the environmental monitoring of Vibrio cholerae

    Le Rouw, Wouter J


    Full Text Available A real-time polymerase chain reaction (PCR) assay utilizing high resolution melt (HRM) curve analysis was developed and tested for the monitoring of Vibrio cholerae in water samples. The assay utilized previously published primers that are specific...

  16. Simultaneous determination of cholecalciferol (vitamin D3) and ergocalciferol (vitamin D2) in foods by selected reaction monitoring.

    Dimartino, Gianluca


    Cholecalciferol (vitamin D3) and ergocalciferol (vitamin D2) were determined simultaneously by selected reaction monitoring (SRM) mass spectrometry for different food matrixes. A small amount of starting sample was saponified and extracted before injection into a linear ion trap mass spectrometer equipped with an atmospheric pressure chemical ionization source. Dihydrotachysterol, which is absent from food and has a structure similar to that of vitamins D3 and D2, was used as an internal standard. Calibration curves for the 2 vitamins showed linearity with R2 values of 0.9999 and 0.9989 for vitamins D3 and D2, respectively. Limits of detection for vitamins D3 and D2 were 0.5 ng/g (1.3 pmol/g) and 1.75 ng/g (4.4 pmol/g) and limits of quantitation were 1.25 ng/g (3.24 pmol/g), and 3.75 ng/g (9.45 pmol/g), respectively. Accuracy and precision of the method were tested with the infant formula reference standard of the National Institute of Standards and Technology, which showed a relative standard deviation of 6%. Recoveries ranged from 95 to 105%. Several food products were tested with AOAC Method 982.29, which is currently in use for vitamins D3 and D2, and results were comparable within 6%.

  17. Real-Time Optical Monitoring of Flow Kinetics and Gas Phase Reactions Under High-Pressure OMCVD Conditions

    Dietz, N.; McCall, S.; Bachmann, K. J.


    This contribution addresses the real-time optical characterization of gas flow and gas phase reactions as they play a crucial role for chemical vapor phase depositions utilizing elevated and high pressure chemical vapor deposition (HPCVD) conditions. The objectives of these experiments are to validate on the basis of results on real-time optical diagnostics process models simulation codes, and provide input parameter sets needed for analysis and control of chemical vapor deposition at elevated pressures. Access to microgravity is required to retain high pressure conditions of laminar flow, which is essential for successful acquisition and interpretation of the optical data. In this contribution, we describe the design and construction of the HPCVD system, which include access ports for various optical methods of real-time process monitoring and to analyze the initial stages of heteroepitaxy and steady-state growth in the different pressure ranges. To analyze the onset of turbulence, provisions are made for implementation of experimental methods for in-situ characterization of the nature of flow. This knowledge will be the basis for the design definition of experiments under microgravity, where gas flow conditions, gas phase and surface chemistry, might be analyzed by remote controlled real-time diagnostics tools, developed in this research project.

  18. In-depth proteomics of ovarian cancer ascites: combining shotgun proteomics and selected reaction monitoring mass spectrometry.

    Elschenbroich, Sarah; Ignatchenko, Vladimir; Clarke, Blaise; Kalloger, Steve E; Boutros, Paul C; Gramolini, Anthony O; Shaw, Patricia; Jurisica, Igor; Kislinger, Thomas


    Epithelial ovarian cancer (EOC) is the most common gynecological cancer and the ninth most common cancer overall. Major problems associated with EOC include poorly characterized disease progression, disease heterogeneity, lack of early detection markers and the development of chemoresistance. Early detection and treatment of EOC would significantly benefit from routine screening tests on available biofluids. We built on our experience in analyzing ovarian cancer ascites and present an analysis pipeline that combines discovery-based proteomics, bioinformatics prioritization and targeted proteomics quantification using Selected Reaction Monitoring Mass Spectrometry (SRM-MS). Ascitic fluids from patients with serous-type epithelial ovarian cancer were analyzed using comprehensive shotgun proteomics and compared to noncancerous ascitic fluids from patients with benign ovarian tumors. Integration of our data with published mRNA transcriptomic and proteomic data sets led to a panel of 51 candidate proteins. Systematic SRM-MS assay development was performed for a subset of these proteins using both synthetic peptides (13 proteins) and stable isotope labeled standards (4 proteins). Subsequently, precise relative quantification by stable isotope dilution-SRM (SID-SRM) in independent ascites and serum samples was performed as a proof-of-concept validation. The analysis strategy outlined here lays the foundation for future experiments using both larger numbers of patient samples and additional candidate proteins, and provides a template for the proteomics-based discovery of cancer biomarkers.

  19. Automatic polymerase chain reaction product detection system for food safety monitoring using zinc finger protein fused to luciferase.

    Yoshida, Wataru; Kezuka, Aki; Murakami, Yoshiyuki; Lee, Jinhee; Abe, Koichi; Motoki, Hiroaki; Matsuo, Takafumi; Shimura, Nobuaki; Noda, Mamoru; Igimi, Shizunobu; Ikebukuro, Kazunori


    An automatic polymerase chain reaction (PCR) product detection system for food safety monitoring using zinc finger (ZF) protein fused to luciferase was developed. ZF protein fused to luciferase specifically binds to target double stranded DNA sequence and has luciferase enzymatic activity. Therefore, PCR products that comprise ZF protein recognition sequence can be detected by measuring the luciferase activity of the fusion protein. We previously reported that PCR products from Legionella pneumophila and Escherichia coli (E. coli) O157 genomic DNA were detected by Zif268, a natural ZF protein, fused to luciferase. In this study, Zif268-luciferase was applied to detect the presence of Salmonella and coliforms. Moreover, an artificial zinc finger protein (B2) fused to luciferase was constructed for a Norovirus detection system. In the luciferase activity detection assay, several bound/free separation process is required. Therefore, an analyzer that automatically performed the bound/free separation process was developed to detect PCR products using the ZF-luciferase fusion protein. By means of the automatic analyzer with ZF-luciferase fusion protein, target pathogenic genomes were specifically detected in the presence of other pathogenic genomes. Moreover, we succeeded in the detection of 10 copies of E. coli BL21 without extraction of genomic DNA by the automatic analyzer and E. coli was detected with a logarithmic dependency in the range of 1.0×10 to 1.0×10(6) copies.

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

    Wang, Perry G; Zhou, Wanlong


    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.

  1. Quantitation of low molecular weight sugars by chemical derivatization-liquid chromatography/multiple reaction monitoring/mass spectrometry.

    Han, Jun; Lin, Karen; Sequria, Carita; Yang, Juncong; Borchers, Christoph H


    A new method for the separation and quantitation of 13 mono- and disaccharides has been developed by chemical derivatization/ultra-HPLC/negative-ion ESI-multiple-reaction monitoring MS. 3-Nitrophenylhydrazine (at 50°C for 60 min) was shown to be able to quantitatively derivatize low-molecular weight (LMW) reducing sugars. The nonreducing sugar, sucrose, was not derivatized. A pentafluorophenyl-bonded phase column was used for the chromatographic separation of the derivatized sugars. This method exhibits femtomole-level sensitivity, high precision (CVs of ≤ 4.6%) and high accuracy for the quantitation of LMW sugars in wine. Excellent linearity (R(2) ≥ 0.9993) and linear ranges of ∼500-fold for disaccharides and ∼1000-4000-fold for monosaccharides were achieved. With internal calibration ((13) C-labeled internal standards), recoveries were between 93.6% ± 1.6% (xylose) and 104.8% ± 5.2% (glucose). With external calibration, recoveries ranged from 82.5% ± 0.8% (ribulose) to 105.2% ± 2.1% (xylulose). Quantitation of sugars in two red wines and two white wines was performed using this method; quantitation of the central carbon metabolism-related carboxylic acids and tartaric acid was carried out using a previously established derivatization procedure with 3-nitrophenylhydrazine as well. The results showed that these two classes of compounds-both of which have important organoleptic properties-had different compositions in red and white wines.

  2. Deciphering chemical interactions between Glycyrrhizae Radix and Coptidis Rhizoma by liquid chromatography with transformed multiple reaction monitoring mass spectrometry.

    Li, Zhenhao; Liu, Ting; Liao, Jie; Ai, Ni; Fan, Xiaohui; Cheng, Yiyu


    In this study, we propose an integrated strategy for the efficient identification and quantification of herbal constituents using liquid chromatography with mass spectrometry. First, liquid chromatography with quadrupole time-of-flight mass spectrometry was employed for the chemical profiling of herbs, where a targeted following nontargeted approach was developed to detect trace constituents by using structural correlations and extracted ion chromatograms. Next, ion pairs and parameters of MS(2) of quadrupole time-of-flight mass spectrometry were selected to design multiple reaction monitoring transitions for the identified compounds on liquid chromatography with triple quadrupole mass spectrometry. The relative concentration of each constituent was then calculated using a semiquantitative calibration curve. The proposed strategy was applied in a study of chemical interactions between Glycyrrhizae Radix and Coptidis Rhizoma. A total of 140 compounds were identified or tentatively characterized from the herbs, 132 of which were relatively quantified. The visualized quantitative results clearly showed codecoction produced significant constituent concentration variations especially for those with a low polarity. The case study also indicated that the present methodology could provide a reliable, accurate, and labor-saving solution for chemical studies of herbal medicines.

  3. Differential Mobility Spectrometry Coupled with Multiple Ion Monitoring in Regulated LC-MS/MS Bioanalysis of a Therapeutic Cyclic Peptide in Human Plasma.

    Fu, Yunlin; Xia, Yuan-Qing; Flarakos, Jimmy; Tse, Francis L S; Miller, Jeffrey D; Jones, Elliott B; Li, Wenkui


    A differential mobility spectrometry (DMS) in combination with a multiple ion monitoring (MIM) method was developed and validated for quantitative LC-MS/MS bioanalysis of pasireotide (SOM230) in human plasma. Pasireotide, a therapeutic cyclic peptide, exhibits poor collision-induced dissociation (CID) efficiency for multiple reaction monitoring (MRM) detection. Therefore, in an effort to increase the overall sensitivity of the assay, a DMS-MIM approach was explored. By selecting the most abundant doubly charged precursor ion in both the Q1 and Q3 of the mass analyzer in MIM and combining the DMS capability to significantly reduce the high matrix/chemical background noise, this new LC-DMS-MIM method overcomes the sensitivity challenge in the typical MRM method due to poor CID fragmentation of the analyte. Human plasma was spiked with pasireotide with concentrations in the range 0.01-50 ng/mL. Weak cation-exchange solid-phase extraction was employed for sample preparation. The sample extracts were analyzed with a SCIEX QTRAP 6500 system equipped with an ESI source and DMS device. The separation voltage and compensation voltage of the DMS and other parameters of the MS system were optimized to maximize signal responses. The performance of the LC-DMS-MIM assay for quantitative analysis of pasireotide in human plasma was evaluated and compared to those obtained via LC-MRM and LC-MIM without DMS. Overall, the assay sensitivity with DMS-MIM was approximately 5-fold better than that observed in MRM or MIM without DMS. The assay was validated with accuracy (% bias) and precision (% CV) of the QC results at eight concentration levels (0.01, 0.02, 0.05, 0.15, 0.3, 1.5, 15, and 37.5 ng/mL) evaluated ranging from -4.8 to 5.0% bias and 0.7 to 8.6% CV for the intraday and interday runs. The current LC-DMS-MIM workflow can be expanded to quantitative analysis of other molecules that have poor fragmentation efficiency in CID.

  4. Discriminative detection of low-abundance point mutations using a PCR/ligase detection reaction/capillary gel electrophoresis method and fluorescence dual-channel monitoring.

    Hamada, Mariko; Shimase, Koji; Tsukagoshi, Kazuhiko; Hashimoto, Masahiko


    We applied a facile LIF dual-channel monitoring system recently developed and reported by our group to the polymerase chain reaction/ligase detection reaction/CGE method for detecting low-abundance point mutations present in a wild-type sequence-dominated population. Mutation discrimination limits and signaling fidelity of the analytical system were evaluated using three mutant variations in codon 12 of the K-ras oncogene that have high diagnostic value for colorectal cancer. We demonstrated the high sensitivity of the present method by detecting rare mutations present among an excess of wild-type alleles (one mutation among ~100 normal sequences). This method also simultaneously interrogated the allelic compositions of the test samples with high specificity through spectral discrimination of the dye-tagged ligase detection reaction products using the dual-channel monitoring system. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  5. Monitoring and Control of a Continuous Grignard Reaction for the Synthesis of an Active Pharmaceutical Ingredient Intermediate Using Inline NIR spectroscopy

    Cervera Padrell, Albert Emili; Nielsen, Jesper; Jønch Pedersen, Michael


    Inline near-infrared (NIR) spectroscopy has been used to monitor a continuous synthesis of an active pharmaceutical ingredient (API) intermediate by a Grignard alkylation reaction. The reaction between a ketone substrate and allylmagnesium chloride may form significant impurities with excess...... feeding of the Grignard reagent beyond the stoichiometric ratio. On the other hand, limiting this reagent would imply a loss in yield. Therefore, accurate dosing of the two reactants is essential. A feedforward–feedback control loop was conceived in order to maintain the reaction as closely as possible...... to the stoichiometric ratio, leading the path to full process automation. The feedback control loop relies on NIR transmission measurements performed in a flow cell where, in contrast to labor-intensive offline HPLC analytical methods, the whole reaction product can be scanned in real time without sample dilution...

  6. CO2-water-mineral reactions during CO2 leakage into glauconitic sands: geochemical and isotopic monitoring of batch experiments

    Humez, P.; Lions, J.; Lagneau, V.; Negrel, Ph.


    experiment; (2) dissolved iron strongly decreases immediately after CO2 injection; (3) potassium, sodium and fluorine concentrations increase at the start of CO2 injection and then stabilize to levels higher than the pre-injection concentrations, (4) chlorides and sulfates are stable. These variations indicate dissolution/precipitation and surface reactions involving mineral phases such as glauconite, siderite/iron hydroxide. The experimental results were interpreted and the geochemical mechanisms involved were included in geochemical modeling using PHREEQC, an essential step to quantify the overall effect of the combined individual reactions and processes. These mechanisms were corroborated with isotopic ratio variations. E.g. the variations of δ13CDIC (from -15.7 ‰ to -21 ‰ vs. PDB) cannot be explained solely by the CO2 dissolution, and indicate additional chemical processes. Likewise, shifts of δ11B towards more negative values stress the implication of the glauconitic minerals, mainly B-bearing phase in the system. These experimental results, and their numerical simulation, are promising for the development of our indirect geochemical and isotopic monitoring technique.

  7. Enhanced sensitivity for selected reaction monitoring mass spectrometry-based targeted proteomics using a dual stage electrodynamic ion funnel interface.

    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


    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.

  8. Quantitative analysis of energy metabolic pathways in MCF-7 breast cancer cells by selected reaction monitoring assay.

    Drabovich, Andrei P; Pavlou, Maria P; Dimitromanolakis, Apostolos; Diamandis, Eleftherios P


    To investigate the quantitative response of energy metabolic pathways in human MCF-7 breast cancer cells to hypoxia, glucose deprivation, and estradiol stimulation, we developed a targeted proteomics assay for accurate quantification of protein expression in glycolysis/gluconeogenesis, TCA cycle, and pentose phosphate pathways. Cell growth conditions were selected to roughly mimic the exposure of cells in the cancer tissue to the intermittent hypoxia, glucose deprivation, and hormonal stimulation. Targeted proteomics assay allowed for reproducible quantification of 76 proteins in four different growth conditions after 24 and 48 h of perturbation. Differential expression of a number of control and metabolic pathway proteins in response to the change of growth conditions was found. Elevated expression of the majority of glycolytic enzymes was observed in hypoxia. Cancer cells, as opposed to near-normal MCF-10A cells, exhibited significantly increased expression of key energy metabolic pathway enzymes (FBP1, IDH2, and G6PD) that are known to redirect cellular metabolism and increase carbon flux through the pentose phosphate pathway. Our quantitative proteomic protocol is based on a mass spectrometry-compatible acid-labile detergent and is described in detail. Optimized parameters of a multiplex selected reaction monitoring (SRM) assay for 76 proteins, 134 proteotypic peptides, and 401 transitions are included and can be downloaded and used with any SRM-compatible mass spectrometer. The presented workflow is an integrated tool for hypothesis-driven studies of mammalian cells as well as functional studies of proteins, and can greatly complement experimental methods in systems biology, metabolic engineering, and metabolic transformation of cancer cells.

  9. Automatic polymerase chain reaction product detection system for food safety monitoring using zinc finger protein fused to luciferase

    Yoshida, Wataru; Kezuka, Aki; Murakami, Yoshiyuki; Lee, Jinhee; Abe, Koichi [Department of Biotechnology and Life Science, Tokyo University of Agriculture and Technology, 2-24-16 Naka-cho, Koganei, Tokyo 184-8588 (Japan); Motoki, Hiroaki; Matsuo, Takafumi; Shimura, Nobuaki [System Instruments Co., Ltd., 776-2 Komiya-cho, Hachioji, Tokyo 192-0031 (Japan); Noda, Mamoru; Igimi, Shizunobu [Division of Biomedical Food Research, National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya-ku, Tokyo 158-8501 (Japan); Ikebukuro, Kazunori, E-mail: [Department of Biotechnology and Life Science, Tokyo University of Agriculture and Technology, 2-24-16 Naka-cho, Koganei, Tokyo 184-8588 (Japan)


    Graphical abstract: -- Highlights: •Zif268 fused to luciferase was used for E. coli O157, Salmonella and coliform detection. •Artificial zinc finger protein fused to luciferase was constructed for Norovirus detection. •An analyzer that automatically detects PCR products by zinc finger protein fused to luciferase was developed. •Target pathogens were specifically detected by the automatic analyzer with zinc finger protein fused to luciferase. -- Abstract: An automatic polymerase chain reaction (PCR) product detection system for food safety monitoring using zinc finger (ZF) protein fused to luciferase was developed. ZF protein fused to luciferase specifically binds to target double stranded DNA sequence and has luciferase enzymatic activity. Therefore, PCR products that comprise ZF protein recognition sequence can be detected by measuring the luciferase activity of the fusion protein. We previously reported that PCR products from Legionella pneumophila and Escherichia coli (E. coli) O157 genomic DNA were detected by Zif268, a natural ZF protein, fused to luciferase. In this study, Zif268–luciferase was applied to detect the presence of Salmonella and coliforms. Moreover, an artificial zinc finger protein (B2) fused to luciferase was constructed for a Norovirus detection system. In the luciferase activity detection assay, several bound/free separation process is required. Therefore, an analyzer that automatically performed the bound/free separation process was developed to detect PCR products using the ZF–luciferase fusion protein. By means of the automatic analyzer with ZF–luciferase fusion protein, target pathogenic genomes were specifically detected in the presence of other pathogenic genomes. Moreover, we succeeded in the detection of 10 copies of E. coli BL21 without extraction of genomic DNA by the automatic analyzer and E. coli was detected with a logarithmic dependency in the range of 1.0 × 10 to 1.0 × 10{sup 6} copies.

  10. Quantitative real-time monitoring of chemical reactions by autosampling flow injection analysis coupled with atmospheric pressure chemical ionization mass spectrometry.

    Zhu, Zhenqian; Bartmess, John E; McNally, Mary Ellen; Hoffman, Ron M; Cook, Kelsey D; Song, Liguo


    Although qualitative and/or semiquantitative real-time monitoring of chemical reactions have been reported with a few mass spectrometric approaches, to our knowledge, no quantitative mass spectrometric approach has been reported so far to have a calibration valid up to molar concentrations as required by process control. This is mostly due to the absence of a practical solution that could well address the sample overloading issue. In this study, a novel autosampling flow injection analysis coupled with an atmospheric pressure chemical ionization mass spectrometry (FIA/APCI-MS) system, consisting of a 1 μL automatic internal sample injector, a postinjection splitter with 1:10 splitting ratio, and a detached APCI source connected to the mass spectrometer using a 4.5 in. long, 0.042 in. inner diameter (ID) stainless-steel capillary, was thus introduced. Using this system together with an optional FIA solvent modifier, e.g., 0.05% (v/v) isopropylamine, a linear quantitative calibration up to molar concentration has been achieved with 3.4-7.2% relative standard deviations (RSDs) for 4 replicates. As a result, quantitative real-time monitoring of a model reaction was successfully performed at the 1.63 M level. It is expected that this novel autosampling FIA/APCI-MS system can be used in quantitative real-time monitoring of a wide range of reactions under diverse reaction conditions.

  11. In situ monitoring of the acetylene decomposition and gas temperature at reaction conditions for the deposition of carbon nanotubes using linear Raman scattering.

    Reinhold-López, Karla; Braeuer, Andreas; Popovska, Nadejda; Leipertz, Alfred


    To understand the reaction mechanisms taking place by growing carbon nanotubes via the catalytic chemical vapor deposition process, a strategy to monitor in situ the gas phase at reaction conditions was developed applying linear Raman spectroscopy. The simultaneous determination of the gas temperature and composition was possible by a new strategy of the evaluation of the Raman spectra. In agreement to the well-known exothermic decomposition of acetylene, a gas temperature increase was quantified when acetylene was added to the incident flow. Information about exhaust gas recirculation and location of the maximal acetylene conversion was derived from the composition measurements.

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

    Ramos Hector


    Full Text Available Abstract 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

  13. Influence of Pichia pastoris cellular material on polymerase chain reaction performance as a synthetic biology standard for genome monitoring.

    Templar, Alexander; Woodhouse, Stefan; Keshavarz-Moore, Eli; Nesbeth, Darren N


    Advances in synthetic genomics are now well underway in yeasts due to the low cost of synthetic DNA. These new capabilities also bring greater need for quantitating the presence, loss and rearrangement of loci within synthetic yeast genomes. Methods for achieving this will ideally; i) be robust to industrial settings, ii) adhere to a global standard and iii) be sufficiently rapid to enable at-line monitoring during cell growth. The methylotrophic yeast Pichia pastoris (P. pastoris) is increasingly used for industrial production of biotherapeutic proteins so we sought to answer the following questions for this particular yeast species. Is time-consuming DNA purification necessary to obtain accurate end-point polymerase chain reaction (e-pPCR) and quantitative PCR (qPCR) data? Can the novel linear regression of efficiency qPCR method (LRE qPCR), which has properties desirable in a synthetic biology standard, match the accuracy of conventional qPCR? Does cell cultivation scale influence PCR performance? To answer these questions we performed e-pPCR and qPCR in the presence and absence of cellular material disrupted by a mild 30s sonication procedure. The e-pPCR limit of detection (LOD) for a genomic target locus was 50pg (4.91×10(3) copies) of purified genomic DNA (gDNA) but the presence of cellular material reduced this sensitivity sixfold to 300pg gDNA (2.95×10(4) copies). LRE qPCR matched the accuracy of a conventional standard curve qPCR method. The presence of material from bioreactor cultivation of up to OD600=80 did not significantly compromise the accuracy of LRE qPCR. We conclude that a simple and rapid cell disruption step is sufficient to render P. pastoris samples of up to OD600=80 amenable to analysis using LRE qPCR which we propose as a synthetic biology standard. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

  14. Global detection and semi-quantification of Fritillaria alkaloids in Fritillariae Ussuriensis Bulbus by a non-targeted multiple reaction monitoring approach.

    Wang, Li; Yao, Zhong Ping; Li, Ping; Chen, Si-Bao; So, Pui-Kin; Shi, Zi-Qi; Hu, Bin; Liu, Li-Fang; Xin, Gui-Zhong


    Methods based on triple quadrupole tandem mass spectrometry have been widely used and reported as highly selective and sensitive methods for quantifying substances of herbal medicines. However, most of them were limited to targeted components, due to the difficulties to optimize the multiple reaction monitoring transitions without authentic standards. This study proposed a novel strategy for non-targeted optimization of multiple reaction monitoring method based on the diagnostic ion guided family classifications, tandem mass spectrometry database establishment, and transitions and collision energy screening. Applying this strategy, 59 Fritillaria alkaloids in Fritillariae Ussuriensis Bulbus have been classified, and 51 of these Fritillaria alkaloids were successfully detected by the optimal multiple reaction monitoring method. For semi-quantification, the easy-to-obtain Fritillaria alkaloids of each type, such as verticinone for cevanine type and peimisine for jervine type, were used as the reference standards to calibrate the other Fritillaria alkaloids in the same type. The method was demonstrated a good linearity (R(2) > 0.998) with satisfactory accuracy and precision, and the lower limits of quantification of verticinone and peimisine were estimated to be 0.076 and 0.216 pg, respectively. In addition, the results suggested that the proposed strategy might obtained high quality metabolomics data in discrimination of Fritillaria unibracteata and Fritillaria ussuriensis.

  15. Quantitative analysis of serotonin secreted by human embryonic stem cells-derived serotonergic neurons via pH-mediated online stacking-CE-ESI-MRM.

    Zhong, Xuefei; Hao, Ling; Lu, Jianfeng; Ye, Hui; Zhang, Su-Chun; Li, Lingjun


    A CE-ESI-MRM-based assay was developed for targeted analysis of serotonin released by human embryonic stem cells-derived serotonergic neurons in a chemically defined environment. A discontinuous electrolyte system was optimized for pH-mediated online stacking of serotonin. Combining with a liquid-liquid extraction procedure, LOD of serotonin in the Krebs'-Ringer's solution by CE-ESI-MS/MS on a 3D ion trap MS was0.15 ng/mL. The quantitative results confirmed the serotonergic identity of the in vitro developed neurons and the capacity of these neurons to release serotonin in response to stimulus.

  16. Monitoring of galvanic replacement reaction between silver nanowires and HAuCl4 by in situ transmission X-ray microscopy.

    Sun, Yugang; Wang, Yuxin


    Galvanic replacement reaction between silver nanowires and an aqueous solution of HAuCl(4) has been successfully monitored in real time by using in situ transmission X-ray microscopy (TXM) in combination with a flow cell reactor. The in situ observations clearly show the morphological evolution of the solid silver nanowires to hollow gold nanotubes in the course of the reaction. Careful analysis of the images reveals that the galvanic replacement reaction on the silver nanowires involves multiple steps: (i) local initiation of pitting process; (ii) anisotropic etching of the silver nanowires and uniform deposition of the resulting gold atoms on the surfaces of the nanowires; and (iii) reconstruction of the nanotube walls via an Ostwald ripening process. The in situ TXM represents a promising approach for studying dynamic processes involved in the growth and chemical transformation of nanomaterials in solutions, in particular for nanostructures with dimensions larger than 50 nm.

  17. Monitoring of an esterification reaction by on-line direct liquid sampling mass spectrometry and in-line mid infrared spectrometry with an attenuated total reflectance probe

    Owen, Andrew W.; McAulay, Edith A.J. [WestCHEM, Department of Pure and Applied Chemistry and CPACT, University of Strathclyde, 295 Cathedral Street, Glasgow, G1 1XL (United Kingdom); Nordon, Alison, E-mail: [WestCHEM, Department of Pure and Applied Chemistry and CPACT, University of Strathclyde, 295 Cathedral Street, Glasgow, G1 1XL (United Kingdom); Littlejohn, David, E-mail: [WestCHEM, Department of Pure and Applied Chemistry and CPACT, University of Strathclyde, 295 Cathedral Street, Glasgow, G1 1XL (United Kingdom); Lynch, Thomas P. [WestCHEM, Department of Pure and Applied Chemistry and CPACT, University of Strathclyde, 295 Cathedral Street, Glasgow, G1 1XL (United Kingdom); Lancaster, J. Steven [Hull Research and Technology Centre, BP Chemicals, Hull, HU12 8DS (United Kingdom); Wright, Robert G. [Thermo Fisher Scientific, Winsford, Cheshire, CW7 3GA (United Kingdom)


    Highlights: • High efficiency thermal vaporiser designed and used for on-line reaction monitoring. • Concentration profiles of all reactants and products obtained from mass spectra. • By-product formed from the presence of an impurity detected by MS but not MIR. • Mass spectrometry can detect trace and bulk components unlike molecular spectrometry. - Abstract: A specially designed thermal vaporiser was used with a process mass spectrometer designed for gas analysis to monitor the esterification of butan-1-ol and acetic anhydride. The reaction was conducted at two scales: in a 150 mL flask and a 1 L jacketed batch reactor, with liquid delivery flow rates to the vaporiser of 0.1 and 1.0 mL min{sup −1}, respectively. Mass spectrometry measurements were made at selected ion masses, and classical least squares multivariate linear regression was used to produce concentration profiles for the reactants, products and catalyst. The extent of reaction was obtained from the butyl acetate profile and found to be 83% and 76% at 40 °C and 20 °C, respectively, at the 1 L scale. Reactions in the 1 L reactor were also monitored by in-line mid-infrared (MIR) spectrometry; off-line gas chromatography (GC) was used as a reference technique when building partial least squares (PLS) multivariate calibration models for prediction of butyl acetate concentrations from the MIR spectra. In validation experiments, good agreement was achieved between the concentration of butyl acetate obtained from in-line MIR spectra and off-line GC. In the initial few minutes of the reaction the profiles for butyl acetate derived from on-line direct liquid sampling mass spectrometry (DLSMS) differed from those of in-line MIR spectrometry owing to the 2 min transfer time between the reactor and mass spectrometer. As the reaction proceeded, however, the difference between the concentration profiles became less noticeable. DLSMS had advantages over in-line MIR spectrometry as it was easier to


    Sreenivasa Rao


    Full Text Available AIMS: This study was conducted to evaluate and compare the efficacy of two sequential sessions of tumescent analgesia in modified radical mastectomy patients for immediate postoperative pain relief. MATERIALS AND METHODS: In this prospective randomized controlled study 100 patients treated by MRM for operable breast carcinoma in S.V.R.R.G.G. Hospital and Sri Venkateswara Medical College , Tirupati , were included in the study. They were evaluated for two consecutive sessions of tumescent analgesia. Session I involved infiltration of 20 cc of 0.25% bupivacaine subcutaneously in to the incisional area plus wound i nstillation of 100 CC of 0.4% xylocaine with adrenaline with 1 mg of butorphanol through the axillary drains. Pain was assessed every 30 minutes by using visual analogue scale ( VAS . Pain of VAS - 3 was taken as cut off point and session II of wound instillation ( 100 CC of 0.4% xylocaine with adrenaline with 1 mg of butorphanol through the axillary drains alone was executed. The efficacy of these two methods of tumescent analgesia was assessed and compared. Statistical analysis was performe d using SPSS version. RESULTS : Session I tumescent analgesia conferred 9 to 10 hours of pain relief and session II for 7 to 8 hours. CONCLUSION : Incisional infiltration of bupivacaine showed cumulative effect and imporved the quality and duration of analgesia in MRM patients in the immediate postoperative period . Tumescent analgesia is a simple and effective means of providing good postoperative pain relief without any major side - effects.

  19. alpha1-acid glycoprotein as a putative biomarker for monitoring the development of the type II reactional stage of leprosy.

    Gupta, Nishma; Shankernarayan, Nallakandy P; Dharmalingam, Kuppamuthu


    Leprosy, a spectral disease manifested on the basis of host immune responses, is complicated by its reactional stages, namely type I reversal reaction (RR) and type II erythema nodosum leprosum (ENL). These reactional stages are characterized by uncontrolled and aberrant immune responses. Biomarkers for reactional stages would aid in early diagnosis, efficient treatment, prevention of neurological complications and prediction of predisposition to reactional stages. In this study, comparative analysis of the serum proteome of leprosy patients by two-dimensional electrophoresis (2DE) followed by mass spectrometry showed differential expression of acute-phase protein alpha (1)-acid glycoprotein (AGP; also known as orosomucoid). AGP levels in untreated ENL cases were significantly higher than in lepromatous leprosy (LL; a non-reactional disease stage) (P=0.0126), RR (P=0.0176) and healthy controls (P=0.0030). These data were confirmed using ELISA. The levels of AGP decreased to normal levels after treatment with multidrug therapy and thalidomide (P =0.0167). In a follow-up study, AGP levels, which were high in the untreated ENL stage, decreased significantly at 5 days ( P=0.0084) and 21 days (P=0.0027) post-treatment. A stage-dependent increase in AGP in an LL patient who progressed into the ENL stage was also shown. Glycosylation analysis by 2DE showed differential expression of acidic glycoforms of AGP in untreated ENL cases. Changes in AGP concentration and differential expression of isoforms correlated with the inflammatory condition in ENL and also with the treatment regimen. Thus, initial validation of AGP as an ENL-specific biomarker and treatment indicator was shown in this study.

  20. In Situ Solid-State Reactions Monitored by X-ray Absorption Spectroscopy: Temperature-Induced Proton Transfer Leads to Chemical Shifts.

    Stevens, Joanna S; Walczak, Monika; Jaye, Cherno; Fischer, Daniel A


    The dramatic colour and phase alteration with the solid-state, temperature-dependent reaction between squaric acid and 4,4'-bipyridine has been probed in situ with X-ray absorption spectroscopy. The electronic and chemical sensitivity to the local atomic environment through chemical shifts in the near-edge X-ray absorption fine structure (NEXAFS) revealed proton transfer from the acid to the bipyridine base through the change in nitrogen protonation state in the high-temperature form. Direct detection of proton transfer coupled with structural analysis elucidates the nature of the solid-state process, with intermolecular proton transfer occurring along an acid-base chain followed by a domino effect to the subsequent acid-base chains, leading to the rapid migration along the length of the crystal. NEXAFS thereby conveys the ability to monitor the nature of solid-state chemical reactions in situ, without the need for a priori information or long-range order.

  1. Short communication: prospective comparison of qualitative versus quantitative polymerase chain reaction for monitoring virologic treatment failure in HIV-infected patients.

    Jeong, Su Jin; Kim, Min Hyung; Song, Je Eun; Ahn, Jin Young; Kim, Sun Bean; Ann, Hea Won; Kim, Jae Kyung; Choi, Heun; Ku, Nam Su; Han, Sang Hoon; Kim, June Myung; Smith, Davey M; Kim, Hyon-Suk; Choi, Jun Yong


    Less costly but still accurate methods for monitoring HIV treatment response are needed. We prospectively evaluated if a qualitative polymerase chain reaction (PCR) amplification assay for virologic monitoring could maintain accuracy while reducing costs in Seoul, South Korea. We conducted the first prospective study comparing a qualitative PCR amplification of HIV-1 reverse transcriptase (RT) versus a commercial real time PCR assay (i.e., viral load) for virologic monitoring of 150 patients receiving antiretroviral therapy (ART) between November 2011 and August 2012 at an urban hospital in Seoul, South Korea. A total of 215 blood plasma samples from 150 patients receiving ART for more than 6 months were evaluated. Using the individual viral load assay, 12 of 215 (5.6%) plasma samples had more than 500 HIV RNA copies/ml. The qualitative PCR amplification assay detected individual samples with ≥500 HIV RNA copies/ml with 100% sensitivity. The specificities of the qualitative PCR amplification of the HIV-1 RT assay were 94.1%, 93.6%, and 93.2% compared to the real time PCR at 500, 1,000, and 5,000 threshold of HIV RNA copies/ml, respectively, and $24,940 USD would have been saved for 150 patients during 10 months. The qualitative PCR amplification of the HIV-1 RT assay might be a useful approach to effectively monitor patients receiving ART and save resources.

  2. In situ X-ray diffraction monitoring of a mechanochemical reaction reveals a unique topology metal-organic framework.

    Katsenis, Athanassios D; Puškarić, Andreas; Štrukil, Vjekoslav; Mottillo, Cristina; Julien, Patrick A; Užarević, Krunoslav; Pham, Minh-Hao; Do, Trong-On; Kimber, Simon A J; Lazić, Predrag; Magdysyuk, Oxana; Dinnebier, Robert E; Halasz, Ivan; Friščić, Tomislav


    Chemical and physical transformations by milling are attracting enormous interest for their ability to access new materials and clean reactivity, and are central to a number of core industries, from mineral processing to pharmaceutical manufacturing. While continuous mechanical stress during milling is thought to create an environment supporting nonconventional reactivity and exotic intermediates, such speculations have remained without proof. Here we use in situ, real-time powder X-ray diffraction monitoring to discover and capture a metastable, novel-topology intermediate of a mechanochemical transformation. Monitoring the mechanochemical synthesis of an archetypal metal-organic framework ZIF-8 by in situ powder X-ray diffraction reveals unexpected amorphization, and on further milling recrystallization into a non-porous material via a metastable intermediate based on a previously unreported topology, herein named katsenite (kat). The discovery of this phase and topology provides direct evidence that milling transformations can involve short-lived, structurally unusual phases not yet accessed by conventional chemistry.

  3. Peripheral Blood Leukocytes and Serum Nested Polymerase Chain Reaction Are Complementary Methods for Monitoring Active Cytomegalovirus Infection in Transplant Patients

    PD Andrade


    Full Text Available BACKGROUND: Human cytomegalovirus is an important cause of morbidity and mortality in immunocompromised patients. Qualitative polymerase chain reaction (PCR has proven to be a sensitive and effective technique in defining active cytomegalovirus infection, in addition to having low cost and being a useful test for situations in which there is no need for quantification. Real-time PCR has the advantage of quantification; however, the high cost of this methodology makes it impractical for routine use.

  4. 常见预防接种异常反应及监测分析%Monitoring Analysis of Abnormal Reaction and Common Inoculation



    Objective To analysis the common abnormal vaccination reaction and response to these anomalies reasonable monitor-ing, promote the scientific and reasonable getting vaccinated. Methods In April 2012 to December, the region of vaccination vac-cine were retrospectively analyzed. Results The region between Apr 2012 and Dec 14387 cases was preventive vaccination, 106 cases suspected immunization abnormal reaction occurred, was 0.74%. With the general reaction was 85 cases, was 80.2%, abnor-mal reaction 15 cases, was 14.2%. No quality accident of vaccine, vaccination accidents. The general reaction, mainly was the fever/red/induration 73 cases (85.9%), followed by allergic skin rashes 5 cases, was 5.9%;Abnormal reaction angioedema was most 10 cases, was 66.7%.Conclusion The region of inoculation against common abnormal reaction and monitoring analysis can reduce the adverse reaction appeared in the process of vaccination, improve the success rate of vaccination.%目的:分析常见预防接种异常反应并对这些异常反应进行合理的监测,促进科学合理的进行预防接种。方法于2012年2~12月对该地区预防接种的疫苗进行了回顾性分析。结果该地区2012年2~12月共预防接种疫苗14387例,发生疑似预防接种异常反应106例,发生率为0.74%。其中以一般反应为多见,共85例,占80.2%,异常反应15例,占14.2%。无疫苗质量事故、预防接种事故发生。发生不良反应的106例中,85例为一般反应,主要是发热/红肿/硬结73例,占85.9%,其次是过敏性皮疹5例,占5.9%;异常反应中最多的是血管性水肿为10例,占异常反应总数的66.7%。结论对该地区的常见预防接种异常反应及监测分析可以减少预防接种过程中出现的不良反应,提高接种的成功率。

  5. Photosynthesis light-independent reactions are sensitive biomarkers to monitor lead phytotoxicity in a Pb-tolerant Pisum sativum cultivar.

    Rodriguez, Eleazar; da Conceição Santos, Maria; Azevedo, Raquel; Correia, Carlos; Moutinho-Pereira, José; Ferreira de Oliveira, José Miguel Pimenta; Dias, Maria Celeste


    Lead (Pb) environmental contamination remains prevalent. Pisum sativum L. plants have been used in ecotoxicological studies, but some cultivars showed to tolerate and accumulate some levels of Pb, opening new perspectives to their use in phytoremediation approaches. However, the putative use of pea plants in phytoremediation requires reliable toxicity endpoints. Here, we evaluated the sensitivity of a large number of photosynthesis-related biomarkers in Pb-exposed pea plants. Plants (cv. "Corne de Bélier") were exposed to Pb concentrations up to 1,000 mg kg(-1) soil during 28 days. The photosynthetic potential biomarkers that were analyzed included pigments, chlorophyll (Chl) a fluorescence, gas exchange, ribulose-1,5-bisphosphate carboxylase/oxygenase (RuBisCO) activity, and carbohydrates. Flow cytometry (FCM) was also used to assess the morpho-functional status of chloroplasts. Finally, Pb-induced nutrient disorders were also evaluated. Net CO2 assimilation rate (A) and RuBisCO activity decreased strongly in Pb-exposed plants. Plant dry mass (DM) accumulation, however, was only reduced in the higher Pb concentrations tested (500 and 1,000 mg kg(-1) soil). Pigment contents increased solely in plants exposed to the largest Pb concentration, and in addition, the parameters related to the light-dependent reactions of photosynthesis, Fv/Fm and ΦPSII, were not affected by Pb exposure. In contrast to this, carbohydrates showed an overall tendency to increase in Pb-exposed plants. The morphological status of chloroplasts was affected by Pb exposure, with a general trend of volume decrease and granularity increase. These results point the endpoints related to the light-independent reactions of photosynthesis as more sensitive predictors of Pb-toxicity than the light-dependent reactions ones. Among the endpoints related to the light-independent photosynthesis reactions, RuBisCO activity and A were found to be the most sensitive. We discuss here the advantages of using

  6. Dynamic transformation of small Ni particles during methanation of CO2 under fluctuating reaction conditions monitored by operando X-ray absorption spectroscopy

    Mutz, B.; Carvalho, H. W. P.; Kleist, W.; Grunwaldt, J.-D.


    A 10 wt.-% Ni/Al2O3 catalyst with Ni particles of about 4 nm was prepared and applied in the methanation of CO2 under dynamic reaction conditions. Fast phase transformations between metallic Ni, NiO and NiCO3 were observed under changing reaction atmospheres using operando X-ray absorption spectroscopy (XAS). Removing H2 from the feed gas and, thus, simulating a H2 dropout during the methanation reaction led to oxidation of the active sites. The initial reduced state of the Ni particles could not be recovered under methanation atmosphere (H2/CO2 = 4); this was only possible with an effective reactivation step applying H2 at increased temperatures. Furthermore, the cycling of the gas atmospheres resulted in a steady deactivation of the catalyst. Operando XAS is a powerful tool to monitor these changes and the behavior of the catalyst under working conditions to improve the understanding of the catalytic processes and deactivation phenomena.

  7. Monitoring the efficacy of specific treatment in chronic Chagas disease by polymerase chain reaction and flow cytometry analysis

    Sánchez G.; Coronado X.; Zulantay I.; Apt W.; Gajardo M.; Solari S.; Venegas J.


    PCR and FC-ALTA were used to monitor parasite clearance in 54 chronic chagasic patients who had completed therapy with allopurinol (ALLO, n = 31) or itraconazole (ITRA, n = 23) ten years earlier. All patients maintained positive conventional serology. 25 of them showed positive XD (ALLO, n = 11 and ITRA, n = 14) and 29 negative XD (ALLO, n = 20 and ITRA, n = 9). 43 patients were positive by both techniques (ALLO, n = 23 and ITRA, n = 20). Seven of 54 patients were negative by PCR and positive...

  8. In situ nucleophilic substitution reaction of N,N-dialkylaminoethyl-2-chlorides monitored by gas chromatography/mass spectrometry.

    Lakshmi, V V S; Reddy, T Jagadeshwar; Murty, M R V S; Prabhakar, S; Vairamani, M


    The detection and identification of degradation products of scheduled chemicals, which are characteristic markers of Chemical Warfare agents (CWAs), plays a key role in verification analysis. Identification of such non-scheduled but specific markers of CWAs helps in deciphering the kind of agent that was present in the sample submitted for off-site analysis. This paper describes the stability of N,N-dialkylaminoethyl-2-chlorides, which are precursors for highly toxic chemicals like VX, in different solvents. These compounds are stable in chloroform, acetonitrile, hexane and dichloromethane but tend to undergo in situ nucleophilic substitution reaction in the presence of alcohols giving the corresponding alkyl ether. The study shows that N,N-dialkylaminoethyl alkyl ethers can be used as markers of N,N-dialkylaminoethyl-2-chlorides. A detailed degradation study of these compounds in the presence of alcohols was carried out and it was found that the reaction follows pseudo-first order kinetics. Electron ionization mass spectral data for the methyl ethers of all the compounds are briefly discussed.

  9. Silver Nanoprism-Loaded Eggshell Membrane: A Facile Platform for In Situ SERS Monitoring of Catalytic Reactions

    Yaling Li


    Full Text Available We reported the fabrication of an in situ surface-enhanced Raman scattering (SERS monitoring platform, comprised of a porous eggshell membrane (ESM bioscaffold loaded with Ag nanoprism via an electrostatic self-assembly approach. The localized surface plasmon resonance (LSPR property of silver nanoprism leads to the blue color of the treated ESMs. UV-vis diffuse reflectance spectroscopy, scanning electron microscope (SEM, X-ray diffraction (XRD and X-ray photoelectron spectroscopy (XPS measurements were employed to observe the microstructure and surface property of Ag nanoprisms on the ESMs. The silver nanoprism-loaded eggshell membrane (AgNP@ESM exhibited strong catalytic activity for the reduction of 4-nitrophenol by sodium borohydride (NaBH4 and it can be easily recovered and reused for more than six cycles. Significantly, the composites also display excellent SERS efficiency, allowing the in situ SERS monitoring of molecular transformation in heterogeneous catalysis. The results indicate that the AgNP@ESM biocomposite can achieve both SERS and catalytic functionalities simultaneously in a single entity with high performance, which promotes the potential applications of ESM modified with functional materials.

  10. 浅谈我院药品不良反应的监测及管理现状%Status monitoring and management of adverse drug reaction

    高寿宝; 邢娟


    目的:探讨我院药品不良反应的监测及管理现状。方法对患者实行药品的不良反应监测,包括分类方法、现状分析等措施,同时对处方药与非处方药的管理现状、抗生素的应用现状及执业药师的执业现状进行分别进行现状探讨、对药品分类管理实施中存在着的问题及时加以解决。结果经过实行药品的不良反应监测及药品的分类管理,有效地加强对处方药的监督管理,防止消费者因自我行为不当导致滥用、误用药物,危及生命健康,消除安全用药的隐患。最重要的是有利于克服药品的使用不当或药品滥用而造成的用药危害及资源浪费,保证人民的用药安全。结论通过药品的不良反应监测与分类管理对安全用药可得到明显的治疗效果,不良反应的发生率低,且用药安全有效。%Objective to investigate the status of monitoring and management of adverse drug reaction in our hospital. Monitoring of adverse reaction method to implement thedrugs to patients, including classification, analysis of the current situation of such measures, the prescription and non prescription drugs management status, antibioticapplication status and licensed pharmacist practicingstatus respectively, on the status of drug classificationmanagement implementation exists the question to be addressed in a timely manner. Results after classificationmanagement monitoring and adverse drug reactions todrugs, effectively strengthen the supervision and management of prescription drugs, to prevent consumers from the self misconduct lead to abuse, misuse of drugs,endangering the life and health, eliminate the drug safetyhidden danger. the most important is to overcome drugor drug abuse caused by improper use of the drug harm and the waste of resources, ensure the people's drug safety. Conclusion the adverse reaction monitoring anddrug classification management of safe medication can obtain

  11. Site-specific growth of Au-Pd alloy horns on Au nanorods: A platform for highly sensitive monitoring of catalytic reactions by surface enhancement raman spectroscopy

    Huang, Jianfeng


    Surface-enhanced Raman scattering (SERS) is a highly sensitive probe for molecular detection. The aim of this study was to develop an efficient platform for investigating the kinetics of catalytic reactions with SERS. To achieve this, we synthesized a novel Au-Pd bimetallic nanostructure (HIF-AuNR@AuPd) through site-specific epitaxial growth of Au-Pd alloy horns as catalytic sites at the ends of Au nanorods. Using high-resolution electron microscopy and tomography, we successfully reconstructed the complex three-dimensional morphology of HIF-AuNR@AuPd and identified that the horns are bound with high-index {11l} (0.25 < l < 0.43) facets. With an electron beam probe, we visualized the distribution of surface plasmon over the HIF-AuNR@AuPd nanorods, finding that strong longitudinal surface plasmon resonance concentrated at the rod ends. This unique crystal morphology led to the coupling of high catalytic activity with a strong SERS effect at the rod ends, making HIF-AuNR@AuPd an excellent bifunctional platform for in situ monitoring of surface catalytic reactions. Using the hydrogenation of 4-nitrothiophenol as a model reaction, we demonstrated that its first-order reaction kinetics could be accurately determined from this platform. Moreover, we clearly identified the superior catalytic activity of the rod ends relative to that of the rod bodies, owing to the different SERS activities at the two positions. In comparison with other reported Au-Pd bimetallic nanostructures, HIF-AuNR@AuPd offered both higher catalytic activity and greater detection sensitivity. © 2013 American Chemical Society.

  12. Recurrence of adverse drug reactions following inappropriate re-prescription: better documentation, availability of information and monitoring are needed.

    van der Linden, Carolien M J; Jansen, Paul A F; van Marum, Rob J; Grouls, René J E; Korsten, Erik H M; Egberts, Antoine C G


    Adverse drug reactions (ADRs) are a common, and often preventable, cause of hospital admission, especially in the elderly, and can occur during hospitalization. In this current opinion article, we present three cases of recurrence of a serious ADR due to re-prescription of a withdrawn medication that highlight the need for a system to prevent the undesirable re-prescription of medications withdrawn because of an ADR. In addition, we describe an electronic system that could help prevent undesirable re-prescription following an ADR. Such a system should document ADRs systematically at the patient level, make this information available to relevant healthcare providers and the patient, and flag re-prescription of the offending drug. The effectiveness and cost effectiveness of such a system would need to be determined.

  13. Monitoring the dissolution process of metals in the gas phase: reactions of nanoscale Al and Ga metal atom clusters and their relationship to similar metalloid clusters.

    Burgert, Ralf; Schnöckel, Hansgeorg


    Formation and dissolution of metals are two of the oldest technical chemical processes. On the atomic scale, these processes are based on the formation and cleavage of metal-metal bonds. During the past 15 years we have studied intensively the intermediates during the formation process of metals, i.e. the formation of compounds containing many metal-metal bonds between naked metal atoms in the center and ligand-bearing metal atoms at the surface. We have called the clusters metalloid or, more generally, elementoid clusters. Via a retrosynthetic route, the many different Al and Ga metalloid clusters which have been structurally characterized allow us to understand also the dissolution process; i.e. the cleavage of metal-metal (M-M) bonds. However, this process can be detected much more directly by the reaction of single metal atom clusters in the gas phase under high vacuum conditions. A suitable tool to monitor the dissolution process of a metal cluster in the gas phase is FT-ICR (Fourier transform ion cyclotron resonance) mass spectrometry. Snapshots during these cleavage processes are possible because only every 1-10 s is there a contact between a cluster molecule and an oxidizing molecule (e.g. Cl2). This period is long, i.e. the formation of the primary product (a smaller metal atom cluster) is finished before the next collision happens. We have studied three different types of reaction:(1) Step-by-step fragmentation of a structurally known metalloid cluster allows us to understand the bonding principle of these clusters because in every step only the weakest bond is broken.(2) There are three oxidation reactions of an Al13(-) cluster molecule with Cl2, HCl and O2 central to this review. These three reactions represent three different reaction types, (a) an exothermic reaction (Cl2), (b) an endothermic reaction (HCl), and (c) a kinetically limited reaction based on spin conservation rules (O2).(3) Finally, we present the reaction of a metalloid cluster with Cl2

  14. Interrater agreement of two adverse drug reaction causality assessment methods: A randomised comparison of the Liverpool Adverse Drug Reaction Causality Assessment Tool and the World Health Organization-Uppsala Monitoring Centre system

    Mehta, Ushma; Rossiter, Dawn P.; Maartens, Gary; Cohen, Karen


    Introduction A new method to assess causality of suspected adverse drug reactions, the Liverpool Adverse Drug Reaction Causality Assessment Tool (LCAT), showed high interrater agreement when used by its developers. Our aim was to compare the interrater agreement achieved by LCAT to that achieved by another causality assessment method, the World Health Organization-Uppsala Monitoring Centre system for standardised case causality assessment (WHO-UMC system), in our setting. Methods Four raters independently assessed adverse drug reaction causality of 48 drug-event pairs, identified during a hospital-based survey. A randomised design ensured that no washout period was required between assessments with the two methods. We compared the methods’ interrater agreement by calculating agreement proportions, kappa statistics, and the intraclass correlation coefficient. We identified potentially problematic questions in the LCAT by comparing raters’ responses to individual questions. Results Overall unweighted kappa was 0.61 (95% CI 0.43 to 0.80) on the WHO-UMC system and 0.27 (95% CI 0.074 to 0.46) on the LCAT. Pairwise unweighted Cohen kappa ranged from 0.33 to 1.0 on the WHO-UMC system and from 0.094 to 0.71 on the LCAT. The intraclass correlation coefficient was 0.86 (95% CI 0.74 to 0.92) on the WHO-UMC system and 0.61 (95% CI 0.39 to 0.77) on the LCAT. Two LCAT questions were identified as significant points of disagreement. Discussion We were unable to replicate the high interrater agreement achieved by the LCAT developers and instead found its interrater agreement to be lower than that achieved when using the WHO-UMC system. We identified potential reasons for this and recommend priority areas for improving the LCAT. PMID:28235001

  15. 3D-MR myelography (3D-MRM) for the diagnosis of lumbal nerve root compression syndrome. A comparison with conventional myelography. 3D-MR Myelographie (3D-MRM) zur Diagnose von lumbalen Nervenwurzelkompressionssyndromen. Vergleichsstudie zu konventioneller Myelographie

    Eberhardt, K.E.W. (Neuroradiologische Abt., Neurochirurgische Klinik, Nuernberg-Erlangen Univ., Erlangen (Germany)); Hollenbach, H.P.; Huk, W.J.


    65 patients with nerve root compression syndrome were examined using a new type of MR-technique, which is comparable to the conventional X-ray myelography. The results of the prospective case study were compared with previous clinical experiences (1). For the examinations a 1.0 T whole body MR-system (Siemens Magnetom Impact) was used. A strong T[sub 2]*-weighted 3D-FISP sequence (TR=73 ms, TE=21 ms, [alpha]=7 ) was applied in sagittal orientation using a circularly polarized oval spine coil. To obtain fat suppression a frequency selective 1-3-3-1 prepulse was applied prior to the imaging sequence. The acquired 3D-data set was evaluated using a Maximum Intensity Projection (MIP) program. Our results confirmed earlier experiences which showed that the diagnostic sensitivity of 3D-MR myelography (3D-MRM) is comparable to that of conventional X-ray myelography. In cases of severe spinal canal stenosis and spondylolisthesis, and in cases of postoperative scar tissue with nerve root compressions, the sensitivity of the 3D-MRM is higher as compared to that of conventional X-ray myelography. (orig.)

  16. Determination of the enantiomer ratio of PBB 149 by GC/NICI-tandem mass spectrometry in the selected reaction monitoring mode

    Recke, R. von der; Goetsch, A.; Vetter, W. [Hohenheim Univ., Stuttgart (Germany). Inst. fuer Lebensmittelchemie; Mariussen, E. [Norwegian Inst. for Air Research, Kjeller (Norway); Berger, U.; Herzke, D. [NILU, The Polar Environmental Centre, Tromso (Norway)


    Technical mixtures of polybrominated biphenyls (PBBs) have been extensively used as flameretardants in textile and electronic industries and as additives in plastics. Despite a continuous reduction of the worldwide annual production in the last decade, the presence of PBBs in the environment was recently confirmed in a wide range of samples. PBBs exist in a theoretical variety of 209 congeners. Many di-ortho, tri-ortho, and tetra-ortho PBBs form stable pairs of enantiomers, which was experimentally confirmed by enantioselective HPLC separation of chiral PBB in a technical mixture. It is known from the literature, that chiral organohalogen compounds can be degraded enantioselectively. In this work we used a chiral GC stationary phase and developed a method using GC/NICI-MSMS in the single reaction monitoring mode for the determination of the enantioratio of PBB 149 in extracts from Norwegian bird of prey eggs.

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

    Bundgaard, Louise; Bendixen, Emøke; Sørensen, Mette Aa


    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...... 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...

  18. Monitoring dynamic reactions of red blood cells to UHF electromagnetic waves radiation using a novel micro-imaging technology.

    Ruan, Ping; Yong, Junguang; Shen, Hongtao; Zheng, Xianrong


    Multiple state-of-the-art techniques, such as multi-dimensional micro-imaging, fast multi-channel micro-spetrophotometry, and dynamic micro-imaging analysis, were used to dynamically investigate various effects of cell under the 900 MHz electromagnetic radiation. Cell changes in shape, size, and parameters of Hb absorption spectrum under different power density electromagnetic waves radiation were presented in this article. Experimental results indicated that the isolated human red blood cells (RBCs) do not have obviously real-time responses to the ultra-low density (15 μW/cm(2), 31 μW/cm(2)) electromagnetic wave radiation when the radiation time is not more than 30 min; however, the cells do have significant reactions in shape, size, and the like, to the electromagnetic waves radiation with power densities of 1 mW/cm(2) and 5 mW/cm(2). The data also reveal the possible influences and statistical relationships among living human cell functions, radiation amount, and exposure time with high-frequency electromagnetic waves. The results of this study may be significant on protection of human being and other living organisms against possible radiation affections of the high-frequency electromagnetic waves.

  19. Adverse drug reaction monitoring with angiotensin converting enzyme inhibitors: A prospective, randomized, open-label, comparative study.

    Sangole, Nishant V; Dadkar, Vaishali N


    Angiotensin converting enzyme inhibitors (ACEIs) are known to possess different chemical structures, and change in structure of a drug can bring about change in its adverse drug reaction (ADR) profile. The study aims to observe the incidence and severity of ADRs between the di-carboxyl group containing ACEIs (d-ACEIs) versus phosphonate group containing ACEIs (p-ACEIs), in patients suffering from essential hypertension. One hundred and twenty patients with essential hypertension were randomized into four groups receiving enalapril, lisinopril, ramipril, and fosinopril. They were followed up for four months, to observe the clinical efficacy along with the associated ADRs. Mild, dry brassy cough (% incidence; 95% CI) was observed with d-ACEIs (6.6%; 0 to 15.6) versus p-ACEI (20%; 5.7 to 34.3), in which the cough observed was moderate-to-severe in intensity and two patients required treatment discontinuation (P ACEIs, whereas, two patients on p-ACEI (6.6%; 0 to15.6) had hypotension (P ACEIs had nausea, which was not observed with p-ACEI treatment (0%) (P ACEIs may have a probable relationship with increase in the incidence and severity of ADRs such as dry brassy cough and hypotension. The di-carboxyl group in d-ACEIs may have a probable relationship with increase in the incidence of ADRs like nausea.

  20. The Dutch Brucella abortus monitoring programme for cattle: the impact of false-positive serological reactions and comparison of serological tests.

    Emmerzaal, A; de Wit, J J; Dijkstra, Th; Bakker, D; van Zijderveld, F G


    The Dutch national Brucella abortus eradication programme for cattle started in 1959. Sporadic cases occurred yearly until 1995; the last infected herd was culled in 1996. In August 1999 the Netherlands was declared officially free of bovine brucellosis by the European Union. Before 1999, the programme to monitor the official Brucella-free status of bovine herds was primarily based on periodical testing of dairy herds with the milk ring test (MRT) and serological testing of all animals older than 1 year of age from non-dairy herds, using the micro-agglutination test (MAT) as screening test. In addition, serum samples of cattle that aborted were tested with the MAT. The high number of false positive reactions in both tests and the serum agglutination test (SAT) and complement fixation test (CFT) used for confirmation seemed to result in unnecessary blockade of herds, subsequent testing and slaughter of animals. For this reason, a validation study was performed in which three indirect enzyme-linked immunosorbent assays (ELISAs), the CFT and the SAT were compared using a panel of sera from brucellosis-free cattle, sera from experimentally infected cattle, and sera from cattle experimentally infected with bacteria which are known to induce cross-reactive antibodies (Pasteurella, Salmonella, Yersinia, and Escherichia). Moreover, four ELISAs and the MRT were compared using a panel of 1000 bulk milk samples from Brucella-free herds and 12 milk samples from Brucella abortus- infected cattle. It is concluded that the ELISA obtained from ID-Lelystad is the most suitable test to monitor the brucelosis free status of herds because it gives rise to fewer false-positive reactions than the SAT.

  1. Adverse Drug Reaction Monitoring in a Tertiary Care Psychiatry Setting: A Comparative Study between Inpatients and Outpatients.

    Gummadi, Tejaswi; Harave, Virupaksha Shanmugam; Aiyar, Lakshmi Narayan; RajaLekshmi, Saraswathy Ganesan; Kunnavil, Radhika


    Psychotropic medications are the mainstay of treatment in psychiatric disorders and are associated with ADRs which affect the compliance and treatment course. Previous studies have looked at the frequency, profile of ADRs and their management aspects. However, the systematic comparison between IP and OP was lacking even though there is a prescription pattern difference. Hence this study was aimed to compare the proportion, pattern, severity and resolution of ADRs once detected. This is a hospital based, prospective follow up study done in the psychiatry ward and outpatient setting for a period of 6 months. A total of 491 patients (200 IP, 291 OP) who received psychotropics were monitored in the study. UKU side effect rating scale was used to detect ADRs, WHO - UMC scale for causality, Modified Hartwig and Siegel Scale to assess severity of ADR and CDSCO suspected ADR form for reporting it. Out of 491 patients who were recruited for the study, 83 patients developed ADRs (34 IP, 49 OP, P = 0.963). The mean number of ADRs per patient was found to be higher in IP (IP-2.17±1.14, OP-1.65±1.12, P-0.01). Severe ADRs were observed to be higher IP (IP-67.64%, OP-38.7%, P-0.014) which was statistically significant. There is no statistically significant difference in distribution of ADRs across all age groups (P-0.475). The study results emphasises the need for active pharmacovigilance so that ADRs are detected and managed at the earliest, hence reducing the morbidity and improving compliance. There is also need for systematic long term, multicentric study to further examine and correlatethe observations of our study.

  2. A thermostat chip of indium tin oxide glass substrate for static polymerase chain reaction and in situ real time fluorescence monitoring.

    Wu, Zhi-Yong; Chen, Kun; Qu, Bai-Yan; Tian, Xiao-Xi; Wang, Xiao-Jie; Fang, Fang


    A thermostat chip of indium-tin oxide glass substrate for static chip polymerase chain reaction (PCR) is, for the first time, introduced in this paper. The transparent conductive layer was used as an electro-heating element. Pulse width modulation and fuzzy proportional integration-differentiation algorithm were adopted in the temperature programming of the chip. The temperature distribution was investigated, and a dynamic control precision within +/-2 degrees C was achieved. The highest ramping rates were 37 degrees Cs(-1) for heating and 8 degrees Cs(-1) for cooling with an electric fan. The PCR reaction vials were constructed with polyethylene tubes or poly(dimethylsiloxane) directly on the thermostat chip; the chip had a typical size of 25 mm x 25 mm and a thickness of 1.1mm. Static chip PCR was successfully demonstrated either in a single vial or in an up to 8-parallel array vials. In situ real time fluorescence monitoring during PCR of a lambda DNA fragments (236bp) with SYBR Green I was demonstrated using a blue light emission diode as a light source and a photomultiplier as a detector. The method proposed here is characterized by open access, easy fabrication and low cost. This work could be the basis for developing a portable real time PCR system with disposable chips for point of care tests.

  3. Detection of Onchocerca volvulus in Skin Snips by Microscopy and Real-Time Polymerase Chain Reaction: Implications for Monitoring and Evaluation Activities.

    Thiele, Elizabeth A; Cama, Vitaliano A; Lakwo, Thomson; Mekasha, Sindeaw; Abanyie, Francisca; Sleshi, Markos; Kebede, Amha; Cantey, Paul T


    Microscopic evaluation of skin biopsies is the monitoring and evaluation (M and E) method currently used by multiple onchocerciasis elimination programs in Africa. However, as repeated mass drug administration suppresses microfilarial loads, the sensitivity and programmatic utility of skin snip microscopy is expected to decrease. Using a pan-filarial real-time polymerase chain reaction with melt curve analysis (qPCR-MCA), we evaluated 1) the use of a single-step molecular assay for detecting and identifying Onchocerca volvulus microfilariae in residual skin snips and 2) the sensitivity of skin snip microscopy relative to qPCR-MCA. Skin snips were collected and examined with routine microscopy in hyperendemic regions of Uganda and Ethiopia (N= 500 each) and "residual" skin snips (tissue remaining after induced microfilarial emergence) were tested with qPCR-MCA. qPCR-MCA detected Onchocerca DNA in 223 residual snips: 139 of 147 microscopy(+) and 84 among microscopy(-) snips, suggesting overall sensitivity of microscopy was 62.3% (139/223) relative to qPCR-MCA (75.6% in Uganda and 28.6% in Ethiopia). These findings demonstrate the insufficient sensitivity of skin snip microscopy for reliable programmatic monitoring. Molecular tools such as qPCR-MCA can augment sensitivity and provide diagnostic confirmation of skin biopsies and will be useful for evaluation or validation of new onchocerciasis M and E tools.

  4. Design and realization of white emulsion reaction device monitoring system%白乳胶反应釜监控系统的设计与实现

    刘微; 金太东; 马跃强; 唐忠华


    In order to enhance the automated level and the control precision of the white emulsion production,the monitoring system of the white emulsion reaction device was designed.Taking use of PLC as core controller,matching its expansion unit controls measuring pump,pneumatic valve,temperature and so on,and combining configuration software,PC monitoring control platform is construted.It introduces working principle and design scheme of the system.The movement result indicates that the monitoring system takes some advantages of high control precision,low labour intensity,convenient datas storage and display,and so on.The system has been successfully applied in production in January,2011.%为提高白乳胶生产的自动化水平和控制精度,设计了一套白乳胶反应釜的监控系统。以PLC为核心控制器,配以其扩展的模拟单元控制计量泵、气动阀、温度等,并结合组态软件搭建PC监测控制平台,介绍整个监控系统的工作原理和设计方案。运行结果表明监控系统具有控制精度高、劳动强度低、数据存储显示方便等优点。系统已于2011年1月成功应用于生产。

  5. 避孕药具不良反应监测报告分析%Analysis of monitoring report for contraceptive adverse reactions ZHONG



    Objective To analyze monitoring report for contraceptive adverse reactions, and to provide reference for clinical choice of appropriate contraceptive and development of family planning work. Methods There were 51802 people using contraceptive as study subjects, and analysis was made on monitoring report for their contraceptive adverse reactions. Results A total of 51802 cases of contraceptive were provided with follow-up in 50766 cases as 98.0%. There were 9260 cases of short-term effect oral contraceptive, 128 cases of emergency contraceptive, 16002 cases of nonoxinol external contraceptive, 24564 cases of male condoms, 192 cases of contraceptive foam, and 620 cases of intra uterine device (IUD). Follow-up showed that there were 124 cases with contraceptive adverse reactions of these contraceptives, except male condoms and contraceptive foam. Conclusion Contraceptive has an important role in family planning, while its adverse reactions have influence on clinical effect. Monitoring and follow-up of contraceptive can provide timely information of various contraceptives. Timely judgment and clinical treatment can be applied, thus clinical effects of contraceptives can be improved, and users’safety can also be ensured.%目的:对避孕药具不良反应监测报告进行分析,为临床选取合适的避孕药具提供依据,同时为临床开展计划生育工作提供参考。方法51802例使用避孕药具人员为研究对象,对其不良反应监测报告进行分析。结果共发放避孕药具51802例,随访50766例,随访率为98.0%。其中包括发放短效口服避孕药9260例,紧急避孕药128例,壬苯醇醚外用避孕药16002例,男用安全套24564例,隐形避孕套192例,节育环(IUD)620例,随访过程中发现避孕药具不良反应124例,除男用避孕套、女用隐形避孕套在随访过程中未发现明显的不良反应外,其余均出现不同的不良反应。结论避孕药具是落实节育措施的

  6. Semivolatile organic compounds monitored using a proton transfer reaction mass spectrometer at 200m above ground in rural Netherlands

    Strickland, Jessica; Klinger, Andreas; Herbig, Jens; Holzinger, Rupert


    Semi-volatile organic compounds (SVOCs) are anthropogenically and naturally occurring chemical compounds that have vapor pressures such that they exist in both the gas and condensed phase at room temperature. Due to the fact SVOCs condense easily, they are interesting in the context of organic aerosol formation and these compounds impact atmospheric properties and human health. Proton Transfer Reaction Mass Spectrometry (PTR-MS, resolution 1200 FWHM) is a method that facilitates deeper analysis of SVOCs. Our setup, consisting of a PTR-MS with a time of flight mass spectrometer coupled to a denuder sampler (DS) was stationed as part of the European ACTRIS-2 program at 200m atop the Cabauw tower in the Netherlands as of September, 2016. The DS consists of three denuders in series. The first two denuders are coated with dimethylpolysiloxane (DB1, OD 4mm, 3cm long) and consists of an assemblage of micro-channels (ID 80 micrometer). The third denuder is an activated charcoal monolith of the same dimensions but with larger (thus fewer) channels (ID 800 micrometer). The air sampled at 800mL/min is pulled through these denuders as laminar flow and the SVOCs will collide and condense on the wall. Undesirable wall losses are minimized by using a short and high flow inlet lines. The collected SVOCs are thermally desorbed under a Nitrogen (N2) gas flow and transferred to the PTR-MS through heated lines to avoid re-condensation. Evaluation of the full mass spectra revealed over 200 different compounds in the range 15-500 Da. The majority of the mass of SVOCs was contained in m/z > 100 and typical mixing ratios of the detected SVOCs were a few pmol/mol in ambient air. Discernible contamination from the DB1 coating was detected and therefore, different blank methods have been tested and evaluated using a student T-test. Proper blank correction is an important issue of this method and will be discussed in detail. Data from October 19th, 2016, are used as case studies for analyzing

  7. Morphological features of Tarlov Cyst: a Comparative Study of MRM and Operation%Tarlov囊肿的MRM表现与术中形态学对比

    刘成环; 曹开明; 张蕾; 常时新; 任明思


    目的 通过对Tarlov囊肿的磁共振脊髓造影(MRM)表现与术中形态学比较,探讨MRM对Tarlov囊肿的分型诊断价值.资料与方法 回顾性分析21例术前MRM检查并经手术、病理证实的具有相关临床症状的Tarlov囊肿的MRM表现,比较Tarlov囊肿的MRM与手术分型.结果 21例患者共发现45个囊肿,其中硬膜囊周围型7例,神经根中央型4例,神经根周围型6例,灯笼状4例;MRM对Tarlov囊肿的分型诊断与手术结果有很好地一致性.结论 MRM可以很好地显示Tarlov囊肿,并能准确对其进行分型诊断,有利于术前的疗效评估.

  8. Lumbar spinal stenosis CAD from clinical MRM and MRI based on inter- and intra-context features with a two-level classifier

    Koh, Jaehan; Alomari, Raja S.; Chaudhary, Vipin; Dhillon, Gurmeet


    An imaging test has an important role in the diagnosis of lumbar abnormalities since it allows to examine the internal structure of soft tissues and bony elements without the need of an unnecessary surgery and recovery time. For the past decade, among various imaging modalities, magnetic resonance imaging (MRI) has taken the significant part of the clinical evaluation of the lumbar spine. This is mainly due to technological advancements that lead to the improvement of imaging devices in spatial resolution, contrast resolution, and multi-planar capabilities. In addition, noninvasive nature of MRI makes it easy to diagnose many common causes of low back pain such as disc herniation, spinal stenosis, and degenerative disc diseases. In this paper, we propose a method to diagnose lumbar spinal stenosis (LSS), a narrowing of the spinal canal, from magnetic resonance myelography (MRM) images. Our method segments the thecal sac in the preprocessing stage, generates the features based on inter- and intra-context information, and diagnoses lumbar disc stenosis. Experiments with 55 subjects show that our method achieves 91.3% diagnostic accuracy. In the future, we plan to test our method on more subjects.

  9. Isolation and measurement of the features of arrays of cell aggregates formed by dielectrophoresis using the user-specified Multi Regions Masking (MRM) technique

    Yusvana, Rama; Markx, Gerard H [School of Engineering and Physical Science, Department of Chemical Engineering, Heriot-Watt University, Riccarton Campus, Edinburgh - EH14 4AS (United Kingdom); Headon, Denis, E-mail: [Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Roslin, Midlothian, Edinburgh - EH25 9PS (United Kingdom)


    The use of dielectrophoresis for the construction of artificial skin tissue with skin cells in follicle-like 3D cell aggregates in well-defined patterns is demonstrated. To analyse the patterns produced and to study their development after their formation a Virtual Instrument (VI) system was developed using the LabVIEW IMAQ Vision Development Module. A series of programming functions (algorithms) was used to isolate the features on the image (in our case; the patterned aggregates) and separate them from all other unwanted regions on the image. The image was subsequently converted into a binary version, covering only the desired microarray regions which could then be analysed by computer for automatic object measurements. The analysis utilized the simple and easy-to-use User-Specified Multi-Regions Masking (MRM) technique, which allows one to concentrate the analysis on the desired regions specified in the mask. This simplified the algorithms for the analysis of images of cell arrays having similar geometrical properties. By having a collection of scripts containing masks of different patterns, it was possible to quickly and efficiently develop sets of custom virtual instruments for the offline or online analysis of images of cell arrays in the database.

  10. 同位素内标-多反应监测同步在线质谱全扫描确证火锅料中罂粟壳成分%Determination of poppy ingredients in chafing dish materials by isotopic internal standard coupled with multiple reaction monitoring and online full scan mass spectrometry

    祝伟霞; 孙转莲; 袁萍; 杨冀州; 刘亚风; 孙武勇


    A confirmative method was developed for determining five poppy alkaloids including morphine,codeine,papaverine,tibane,noscapine in chafing dish ingredients by high perform-ance liquid chromatography coupled with triple quadrupole linear ion trap mass spectrometry (HPLC-Q Trap MS). The sample was extracted with dilute HCl solution under heating condi-tion. The removal of lipid procedure was performed with hexane. The purification was carried out on a mixed-cation solid-phase extraction column( MCX)and ethyl acetate-methanol contai-ning 5% aqueous ammonia was used for elution. A PAK ST column was used to separate the analytes,and 5 mmol/L ammonium acetate methanol and 10 mmol/L ammonium acetate( pH 3. 6)were used as mobile phases. The five alkaloids was detected in the positive mode simulta-neously by multiple reaction monitoring ( MRM ) and online enhanced product ion full scan ( EPI). The LODs were 0. 05-0. 5 μg/kg and the LOQs were 0. 2-2 μg/kg for the five poppy alkaloids. The overall recoveries of the method varied from 64. 2% to 110. 6%,and the RSD were between 4. 2% and 12. 5%. The EPI mass spectra of positive samples were searched through standard library for qualitative confirmation. The detection of real hot pot material sam-ples showed this method can be used for the simple and accurate determination of the five pop-py alkaloid residues in chafing dish.%建立了高效液相色谱-三重四极杆线性离子阱质谱测定火锅料中吗啡、可待因、蒂巴因、罂粟碱、那可丁等5种生物碱残留的确证方法。样品采用稀盐酸加热提取,正己烷除脂,阳离子混合机理固相萃取柱净化,5%氨化乙酸乙酯-甲醇洗脱,PAK ST色谱柱分离,5 mmol/L乙酸铵甲醇溶液-10 mmol/L 乙酸铵水溶液( pH 3.6)作为流动相洗脱,电喷雾正离子模式下多反应监测同步增强子离子在线全扫描( EPI)。在该实验条件下,5种生物碱的 LOD在0.05~0.5μg/kg之间,增强型

  11. Quantification of intermediate-abundance proteins in serum by multiple reaction monitoring mass spectrometry in a single-quadrupole ion trap.

    Lin, Shanhua; Shaler, Thomas A; Becker, Christopher H


    A method is presented to quantify intermediate-abundance proteins in human serum using a single-quadrupole linear ion trap mass spectrometer-in contrast, for example, to a triple-quadrupole mass spectrometer. Stable-isotope-labeled (tryptic) peptides are spiked into digested protein samples as internal standards, aligned with the traditional isotope dilution approach. As a proof-of-concept experiment, four proteins of intermediate abundance were selected, coagulation factor V, adiponectin, C-reactive protein (CRP), and thyroxine binding globulin. Stable-isotope-labeled peptides were synthesized with one tryptic sequence from each of these proteins. The normal human serum concentration ranges of these proteins are from 1 to 30 microg/mL (or 20 to 650 pmol/mL). These labeled peptides and their endogenous counterparts were analyzed by LC-MS/MS using multiple reaction monitoring, a multiplexed form of the selected reaction monitoring technique. For these experiments, only one chromatographic dimension (on-line reversed-phase capillary column) was used. Improved limits of detection will result with multidimensional chromatographic methods utilizing more material per sample. Standard curves of the spiked calibrants were generated with concentrations ranging from 3 to 700 pmol/mL using both neat solutions and peptides spiked into the complex matrix of digested serum protein solution where ion suppression effects and interferences are common. Endogenous protein concentrations were determined by comparing MS/MS peak areas of the endogenous peptides to the isotopically labeled internal calibrants. The derived concentrations from a normal human serum pool (neglecting loss of material during sample processing) were 9.2, 110, 120, and 246 pmol/mL for coagulation factor V, adiponectin, CRP, and thyroxine binding globulin, respectively. These concentrations generally agree with the reported normal ranges for these proteins. As a measure of analytical reproducibility of this

  12. Paired emitter-detector diode detection with dual wavelength monitoring for enhanced sensitivity to transition metals in ion chromatography with post-column reaction.

    O' Toole, Martina; Barron, Leon; Shepherd, Roderick; Paull, Brett; Nesterenko, Pavel; Diamond, Dermot


    The combination of post-column derivatisation and visible detection are regularly employed in ion chromatography (IC) to detect poorly absorbing species. Although this mode is often highly sensitive, one disadvantage is the increase in repeating baseline artifacts associated with out-of-sync pumping systems. The work presented here will demonstrate the use of a second generation design paired emitter-detector diode (PEDD-II) detection mode offering enhanced sensitivity to transition metals in IC by markedly reducing this problem and also by improving signal noise. First generation designs demonstrated the use of a single integrated PEDD detector cell as a simple, small (15 x 5 mm), highly sensitive, low cost photometric detector for the detection of metals in IC. The basic principle of this detection mode lies in the employment of two linear light emitting diodes (LEDs), one operating in normal mode as a light source and the other in reverse bias serving as a light detector. The second generation PEDD-II design showed increased sensitivity for Mn(II)- and Co(II)-2-(pyridylazo)resorcinol (PAR) complexes as a result of two simultaneously acquiring detection cells--one analytical PEDD cell and one reference PEDD cell. Therefore, the PEDD-II employs two wavelengths whereby one monitors the analyte reaction product and the second monitors a wavelength close to the isosbestic point. The optimum LED wavelength to be used for the analytical cell was investigated to maximise peak response. The fabrication process for both the analytical and reference PEDD cells was validated by determining the reproducibility of detectors within a batch. The reproducibility and sensitivity of the PEDD-II detector was then investigated using signals obtained from both intra- and inter-day chromatograms.

  13. Unified ZnO Q-dot growth mechanism from simultaneous UV-Vis and EXAFS monitoring of sol-gel reactions induced by different alkali base

    Caetano, Bruno L.; Silva, Marlon N.; Santilli, Celso V.; Briois, Valérie; Pulcinelli, Sandra H.


    This article aims to give experimental evidences of the universality of main steps involved in ZnO nanoparticles formation and growth from sol-gel process. In this way, we revisit the effect of the alkali base (LiOH, NaOH, KOH) used to induce the hydrolysis-condensation reaction in order to unfold the ZnO Q-dot formation mechanisms by using simultaneous time resolved monitoring of zinc species and Q-dot size by combining EXAFS and UV-Vis spectroscopy. Irrespective of the alkali base used, nucleation and growth of ZnO Q-dots occur by consumption of zinc oxy-acetate precursor. Higher amounts of ZnO nanocrystal are produced as the strength of the base increases. After achieving the steady state equilibrium regime the Q-dot growth occurs initially by oriented attachment coalescence mechanism followed by the Ostwald ripening coarsening. The dependence of the formation and growth mechanisms on the base strength allows the fine tuning of the Q-dot size and photoluminescence properties.

  14. Real-time monitoring of respiratory absorption factors of volatile organic compounds in ambient air by proton transfer reaction time-of-flight mass spectrometry

    Huang, Zhonghui [State Key Laboratory of Organic Geochemistry and Guangdong Key Laboratory of Environmental Protection and Resources Utilization, Guangzhou Institute of Geochemistry, Chinese Academy of Sciences, Guangzhou 510640 (China); University of Chinese Academy of Sciences, Beijing 100049 (China); Zhang, Yanli [State Key Laboratory of Organic Geochemistry and Guangdong Key Laboratory of Environmental Protection and Resources Utilization, Guangzhou Institute of Geochemistry, Chinese Academy of Sciences, Guangzhou 510640 (China); Center for Excellence in Urban Atmospheric Environment, Institute of Urban Environment, Chinese Academy of Sciences, Xiamen 361021 (China); Yan, Qiong [Department of Respiratory Diseases, Guangzhou No. 12 People' s Hospital, Guangzhou 510620 (China); Zhang, Zhou [State Key Laboratory of Organic Geochemistry and Guangdong Key Laboratory of Environmental Protection and Resources Utilization, Guangzhou Institute of Geochemistry, Chinese Academy of Sciences, Guangzhou 510640 (China); Wang, Xinming, E-mail: [State Key Laboratory of Organic Geochemistry and Guangdong Key Laboratory of Environmental Protection and Resources Utilization, Guangzhou Institute of Geochemistry, Chinese Academy of Sciences, Guangzhou 510640 (China); Center for Excellence in Urban Atmospheric Environment, Institute of Urban Environment, Chinese Academy of Sciences, Xiamen 361021 (China)


    Respiratory absorption factors (AFs) are essential parameters in the evaluation of human health risks from toxic volatile organic compounds (VOCs) in ambient air. A method for the real time monitoring of VOCs in inhaled and exhaled air by proton transfer reaction time-of-flight mass spectrometry (PTR-TOF-MS) has been developed to permit the calculation of respiratory AFs of VOCs. Isoprene was found to be a better breath tracer than O{sub 2}, CO{sub 2}, humidity, or acetone for distinguishing between the expiratory and inspiratory phases, and a homemade online breath sampling device with a buffer tube was used to optimize signal peak shapes. Preliminary tests with seven subjects exposed to aromatic hydrocarbons in an indoor environment revealed mean respiratory AFs of 55.0%, 55.9%, and 66.9% for benzene, toluene, and C8-aromatics (ethylbenzene and xylenes), respectively. These AFs were lower than the values of 90% or 100% used in previous studies when assessing the health risks of inhalation exposure to hazardous VOCs. The mean respiratory AFs of benzene, toluene and C8-aromatics were 66.5%, 70.2% and 82.3% for the three female subjects; they were noticeably much higher than that of 46.4%, 45.2% and 55.3%, respectively, for the four male subjects.

  15. Stable isotopic internal standard correction for quantitative analysis of hydroxyeicosatetraenoic acids (HETEs) in serum by on-line SPE-LC-MS/MS in selected reaction monitoring mode.

    Fernández-Peralbo, M A; Ferreiro Vera, C; Priego-Capote, F; Luque de Castro, M D


    The influence of the inclusion of a stable isotopic labeled internal standard (SIL-IS) on the quantitative analysis of hydroxyeicosatetranoic acids (HETEs) in human serum is evaluated in this research. A solid-phase extraction-liquid chromatography-tandem mass spectrometry (SPE-LC-MS/MS) platform, one of the preferred approaches for targeted analysis of biofluids through the selected reaction monitoring (SRM) operational mode, was used to determine HETEs. These compounds were chosen as targeted metabolites because of their involvement in cardiovascular disease, cancer and osteoporosis. 15HETE-d8 was chosen as internal standard to evaluate matrix effects. Thus, the physico-chemical properties of the SIL-IS were the basis to evaluate the analytical features of the method for each metabolite through four calibration models. Two of the models were built with standard solutions at different concentration levels, but one of the calibration sets was spiked with an internal standard (IS). The other two models were built with the serum pool from osteoporotic patients, which was spiked at different concentrations with the target analytes. In this case, one of the serum calibration sets was also spiked with the IS. The study shows that the IS allowed noticeable correction of matrix effects for some HETE isomers at certain concentration levels, while accuracy was decreased at low concentration (15ng/mL) of them. Therefore, characterization of the method has been properly completed at different concentration levels. Copyright © 2014 Elsevier B.V. All rights reserved.

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

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


    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.

  17. Use of stable isotope dimethyl labeling coupled to selected reaction monitoring to enhance throughput by multiplexing relative quantitation of targeted proteins.

    Aye, Thin Thin; Low, Teck Yew; Bjørlykke, Yngvild; Barsnes, Harald; Heck, Albert J R; Berven, Frode S


    In this manuscript, we present a proof-of-concept study for targeted relative protein quantitation workflow using chemical labeling in the form of dimethylation, coupled with selected reaction monitoring (dimethyl-SRM). We first demonstrate close to complete isotope incorporation for all peptides tested. The accuracy, reproducibility, and linear dynamic range of quantitation are further assessed based on known ratios of nonhuman standard proteins spiked into human cerebrospinal fluid (CSF) as a model complex matrix. Quantitation reproducibility below 20% (CV < 20%) was obtained for analyte concentrations present at a dynamic range of 4 orders of magnitude lower than that of the background proteins. An error of less than 15% was observed when measuring the abundance of 44 out of 45 major human plasma proteins. Dimethyl-SRM was further examined by comparing the relative quantitation of eight proteins in human CSF with the relative quantitation obtained using synthetic heavy peptides coupled to stable isotope dilution-SRM (SID-SRM). Comparison between the two methods reveals that the correlation between dimethyl-SRM and SID-SRM is within 0.3-33% variation, demonstrating the accuracy of relative quantitation using dimethyl-SRM. Dimethyl labeling coupled with SRM provides a fast, convenient, and cost-effective alternative for relative quantitation of a large number of candidate proteins/peptides.

  18. Application of Selected Reaction Monitoring Mass Spectrometry to Field Grown Crop Plants To Allow Dissection of the Molecular Mechanisms of Abiotic Stress Tolerance.

    Richard P. Jacoby


    Full Text Available One major constraint upon the application of molecular crop breeding approaches is the small number of genes linked to agronomically desirable traits through defined biochemical mechanisms. Proteomic investigations of crop plants under abiotic stress treatments have identified many proteins that differ in control versus stress comparisons, however this broad profiling of cell physiology is poorly suited to ranking the effects and identifying the specific proteins that are causative in agronomically relevant traits. Here we will reason that insights into a protein’s function, its biochemical process and links to stress tolerance are more likely to arise through approaches that evaluate these differential abundances of proteins and include varietal comparisons, precise discrimination of protein isoforms, enrichment of functionally related proteins and integration of proteomic datasets with physiological measurements of both lab and field grown plants. We will briefly explain how applying the emerging proteomic technology of multiplexed selective reaction monitoring mass spectrometry with its accuracy and throughput can facilitate and enhance these approaches and provide a clear means to rank the growing cohort of stress responsive proteins. We will also highlight the benefit of integrating proteomic analyses with cultivar-specific genetic databases and physiological assessments of cultivar performance in relevant field environments for revealing deeper insights into molecular crop improvement.

  19. Accumulation of three important bioactive compounds in different plant parts of Withania somnifera and its determination by the LC-ESI-MS-MS (MRM) method.

    Gajbhiye, Narendra A; Makasana, Jayanti; Kumar, Satyanshu


    A comprehensive experiment was conducted to study the accumulation pattern and determination of three important bioactive compounds namely withaferin-A (WA), 12-deoxywithastramonolide (WO) and withanolide-A (WD) and its determination by the liquid chromatography/electrospray ionization tandem mass spectrometry (LC-ESI-MS-MS) method in root, stem, fruits and leaves of Withania somnifera. A rapid and sensitive LC-ESI-MS-MS method was developed and validated for the determination of these three important bioactive compounds, having same molecular weight. The multiple reaction monitoring method was established by two transitions for each analyte and intense transition used for quantification. Separation of the three analytes was achieved within a run time of 5 min on an RP-18 column using a mobile phase consisting of acetonitrile and 0.1% acetic acid in water in an isocratic condition. The developed method was validated as per the ICH guidelines. The developed method was found to be suitable for identification and quantification of WA, WO and WD in different plant parts such as roots, stems, fruits and leaves of W. somnifera. The accumulation of WA was highest in leaves samples (8.84 ± 0.37 mg/g) and it was 2.23, 5.85 and 27.26 times higher than its concentration in fruits, stems and roots, respectively. WO and WD contents were highest (0.44 ± 0.016 and 0.72 ± 0.016 mg/g, respectively) in root.

  20. Assessment of global reporting of adverse drug reactions for anti-malarials, including artemisinin-based combination therapy, to the WHO Programme for International Drug Monitoring

    Van Erps Jan


    Full Text Available Abstract Background In spite of enhanced control efforts, malaria remains a major public health problem causing close to a million deaths annually. With support from several donors, large amounts of artemisinin-based combination therapy (ACT are being deployed in endemic countries raising safety concerns as little is known about the use of ACT in several of the settings where they are deployed. This project was undertaken to profile the provenance of the pharmacovigilance reporting of all anti-malarials, including ACT to the WHO adverse drug reaction (ADR database (Vigibase™ over the past 40 years. Methods The WHO Programme for International Drug Monitoring, the Uppsala Monitoring Centre (UMC provided anonymized extracts of Vigibase™ covering the period 1968-2008. All countries in the programme were clustered according to their malaria control phase and income status. The number of individual case safety reports (ICSRs of anti-malarials was analyzed according to those clusters. Results From 1968 to 2008, 21,312 ICSRs suspecting anti-malarials were received from 64 countries. Low-income countries, that are also malaria-endemic (categorized as priority 1 countries submitted only 1.2% of the ICSRs. Only 60 out of 21,312 ICSRs were related to ACT, 51 of which were coming from four sub-Saharan African countries. Although very few ICSRs involved artemisinin-based compounds, many of the adverse events reported were potentially serious. Conclusions This paper illustrates the low reporting of ADRs to anti-malarials in general and ACT in particular. Most reports were submitted by non-endemic and/or high-income countries. Given the current mix of large donor funding, the insufficient information on safety of these drugs, increasing availability of ACT and artemisinin-based monotherapies in public and private sector channels, associated potential for inappropriate use and finally a pipeline of more than 10 new novel anti-malarials in various stages of

  1. In cleanroom, sub-ppb real-time monitoring of volatile organic compounds using proton-transfer reaction/time of flight/mass spectrometry

    Hayeck, Nathalie; Maillot, Philippe; Vitrani, Thomas; Pic, Nicolas; Wortham, Henri; Gligorovski, Sasho; Temime-Roussel, Brice; Mizzi, Aurélie; Poulet, Irène


    Refractory compounds such as Trimethylsilanol (TMS) and other organic compounds such as propylene glycol methyl ether acetate (PGMEA) used in the photolithography area of microelectronic cleanrooms have irreversible dramatic impact on optical lenses used on photolithography tools. There is a need for real-time, continuous measurements of organic contaminants in representative cleanroom environment especially in lithography zone. Such information is essential to properly evaluate the impact of organic contamination on optical lenses. In this study, a Proton-Transfer Reaction-Time-of-Flight Mass spectrometer (PTR-TOF-MS) was applied for real-time and continuous monitoring of fugitive organic contamination induced by the fabrication process. Three types of measurements were carried out using the PTR-TOF-MS in order to detect the volatile organic compounds (VOCs) next to the tools in the photolithography area and at the upstream and downstream of chemical filters used to purge the air in the cleanroom environment. A validation and verification of the results obtained with PTR-TOF-MS was performed by comparing these results with those obtained with an off-line technique that is Automated Thermal Desorber - Gas Chromatography - Mass Spectrometry (ATD-GC-MS) used as a reference analytical method. The emerged results from the PTR-TOF-MS analysis exhibited the temporal variation of the VOCs levels in the cleanroom environment during the fabrication process. While comparing the results emerging from the two techniques, a good agreement was found between the results obtained with PTR-TOF-MS and those obtained with ATD-GC-MS for the PGMEA, toluene and xylene. Regarding TMS, a significant difference was observed ascribed to the technical performance of both instruments.

  2. Medication monitoring in a nurse-led respiratory outpatient clinic: pragmatic randomised trial of the West Wales Adverse Drug Reaction Profile.

    Marie E Gabe

    Full Text Available OBJECTIVE: To assess the clinical effect of medication monitoring using the West Wales Adverse Drug Reaction (ADR Profile for Respiratory Medicine. DESIGN: Single-site parallel-arm pragmatic trial using stratified randomisation. SETTING: Nurse-led respiratory outpatient clinic in general hospital in South Wales. PARTICIPANTS: 54 patients with chronic respiratory disease receiving bronchodilators, corticosteroids or leukotriene receptor antagonists. INTERVENTION: Following initial observation of usual nursing care, we allocated participants at random to receive at follow up: either the West Wales ADR Profile for Respiratory Medicine in addition to usual care ('intervention arm' with 26 participants; or usual care alone ('control arm' with 28 participants. MAIN OUTCOME MEASURES: Problems reported and actions taken. RESULTS: We followed up all randomised participants, and analysed data in accordance with treatment allocated. The increase in numbers of problems per participant identified at follow up was significantly higher in the intervention arm, where the median increase was 20.5 [inter-quartile range (IQR 13-26], while that in the control arm was -1 [-3 to +2] [Mann-Whitney U test: z = 6.28, p<0.001]. The increase in numbers of actions per participant taken at follow up was also significantly higher in the intervention arm, where the median increase was 2.5 [1]-[4] while that in the control arm was 0 [-1.75 to +1] [Mann-Whitney U test: z = 4.40, p<0.001]. CONCLUSION: When added to usual nursing care, the West Wales ADR Profile identified more problems and prompted more nursing actions. Our ADR Profile warrants further investigation as a strategy to optimise medication management. TRIAL REGISTRATION: ISRCTN10386209.

  3. Rapid quantification of Escherichia coli in food and media using bacteriophage T7 amplification and liquid chromatography-multiple reaction monitoring tandem mass spectrometry.

    Banu, Mazlina; Ng, Daniel; Zheng, Lu; Goh, Lin-Tang; Bi, Xuezhi; Ow, Dave Siak-Wei


    Conventional microbiological assays have been a valuable tool for specific enumeration of indicative bacteria of relevance to food and public health, but these culture-based methods are time-consuming and require tedious biochemical and morphological identification. In this work, we exploit the ability of bacteriophage T7 to specifically infect Escherichia coli and amplify nearly a 100-fold in 1–2 h. Bacteriophage amplification is integrated with liquid chromatography-multiple reaction monitoring tandem mass spectrometry (LC-MRM–MS/MS) for quantitation of phage-specific peptides. Heavy isotopic 15N labeled T7 is introduced as the inoculum phage and internal standard. Quantification is performed by determining the ratio of phage-specific peptides over the internal standard which value is proportional to E. coli numbers. A broad dynamic range of 6-log orders ranging from 3.0 × 10(3) to 3.0 × 10(9) CFU/ml is attained in LB, while between 4.1 × 10(4)–2.7 × 10(9) CFU/ml and 1.9 × 10(3)–3.0 × 10(7) CFU/ml was enumerated respectively in coconut water and apple juice. With this method, viable E. coli are quantified in 4 h with a detection limit of 3.0 × 10(3) CFU/ml, 4.1 × 10(4) CFU/ml and 1.9 × 10(3) CFU/ml in LB, coconut water and apple juice, respectively. This method has potential as a rapid tool for detection of fecal contamination during food bioprocessing and distribution to safeguard public health.

  4. Magnetic resonance microscopy for monitoring osteogenesis in tissue-engineered construct in vitro

    Xu Huihui [Bioengineering Department (MC 063), University of Illinois at Chicago, 851 South Morgan Street, Chicago, IL 60607-7052 (United States); Othman, Shadi F [Bioengineering Department (MC 063), University of Illinois at Chicago, 851 South Morgan Street, Chicago, IL 60607-7052 (United States); Hong Liu [Bioengineering Department (MC 063), University of Illinois at Chicago, 851 South Morgan Street, Chicago, IL 60607-7052 (United States); Peptan, Ioana A [Bioengineering Department (MC 063), University of Illinois at Chicago, 851 South Morgan Street, Chicago, IL 60607-7052 (United States); Magin, Richard L [Bioengineering Department (MC 063), University of Illinois at Chicago, 851 South Morgan Street, Chicago, IL 60607-7052 (United States)


    Magnetic resonance microscopy (MRM) is used to monitor osteogenesis in tissue-engineered constructs. Measurements of the developing tissue's MR relaxation times (T{sub 1} and T{sub 2}), apparent diffusion coefficient (ADC) and elastic shear modulus were conducted over a 4-week growth period using an 11.74 T Bruker spectrometer with an imaging probe adapted for MR elastography (MRE). Both the relaxation times and the ADC show a statistically significant decrease after only one week of tissue development while the tissue stiffness increases progressively during the first two weeks of in vitro growth. The measured MR parameters are correlated with histologically monitored osteogenic tissue development. This study shows that MRM can provide quantitative data with which to characterize the growth and development of tissue-engineered bone.

  5. 4月9~13日连续暴雨和强对流天气过程成因分析和MRM2等模式预报性能检验%Clause Analysis And MRM2 Forecasting Capillarity Test On The Continuous Rainstorm And Strong Convective Process Occurred On April 9 To 13 2003 In Jiangxi

    毛连海; 刘志雄; 郭达烽



  6. Comparison of pharmacokinetic behavior of two iridoid glycosides in rat plasma after oral administration of crude Cornus officinals and its jiuzhipin by high performance liquid chromatography triple quadrupole mass spectrometry combined with multiple reactions monitoring mode

    Xiaocheng Chen; Gang Cao; Jianping Jiang


    Objective: The present study examined the pharmacokinetic profiles of two iridoid glycosides named morroniside and loganin in rat plasma after oral administration of crude and processed Cornus officinals. Materials and Methods: A rapid, selective and specific high-performance liquid chromatography/electrospray ionization tandem mass spectrometry with multiple reactions monitoring mode was developed to simultaneously investigate the pharmacokinetic profiles of morroniside and loganin in rat pl...

  7. Development of protein biomarkers in cerebrospinal fluid for secondary progressive multiple sclerosis using selected reaction monitoring mass spectrometry (SRM-MS

    Jia Yan


    Full Text Available Abstract Background Multiple sclerosis (MS is a chronic inflammatory disorder of the central nervous system (CNS. It involves damage to the myelin sheath surrounding axons and to the axons themselves. MS most often presents with a series of relapses and remissions but then evolves over a variable period of time into a slowly progressive form of neurological dysfunction termed secondary progressive MS (SPMS. The reasons for this change in clinical presentation are unclear. The absence of a diagnostic marker means that there is a lag time of several years before the diagnosis of SPMS can be established. At the same time, understanding the mechanisms that underlie SPMS is critical to the development of rational therapies for this untreatable stage of the disease. Results Using high performance liquid chromatography-coupled mass spectrometry (HPLC; we have established a highly specific and sensitive selected reaction monitoring (SRM assay. Our multiplexed SRM assay has facilitated the simultaneous detection of surrogate peptides originating from 26 proteins present in cerebrospinal fluid (CSF. Protein levels in CSF were generally ~200-fold lower than that in human sera. A limit of detection (LOD was determined to be as low as one femtomol. We processed and analysed CSF samples from a total of 22 patients with SPMS, 7 patients with SPMS treated with lamotrigine, 12 patients with non-inflammatory neurological disorders (NIND and 10 healthy controls (HC for the levels of these 26 selected potential protein biomarkers. Our SRM data found one protein showing significant difference between SPMS and HC, three proteins differing between SPMS and NIND, two proteins between NIND and HC, and 11 protein biomarkers showing significant difference between a lamotrigine-treated and untreated SPMS group. Principal component analysis (PCA revealed that these 26 proteins were correlated, and could be represented by four principal components. Overall, we established an

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

    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


    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

  9. Experimental cross-sections of deuteron-induced reaction on {sup 89}Y up to 20 MeV; comparison of {sup nat}Ti(d,x){sup 48}V and {sup 27}Al(d,x){sup 24}Na monitor reactions

    Lebeda, Ondřej, E-mail:; Štursa, Jan; Ráliš, Jan


    We measured cross-sections of the deuteron-induced reactions on {sup 89}Y in the energy range of 3.9–19.5 MeV. Excitation functions for formation of {sup 88}Zr, {sup 89m}Zr, {sup 89}Zr, {sup 88}Y, {sup 90m}Y and {sup 87m}Sr were determined and compared with previously published data and prediction of the TALYS code. Thick target yields for production of {sup 88}Zr, {sup 89}Zr{sup cum}, {sup 88}Y, {sup 90m}Y and {sup 87m}Sr were calculated from the measured cross-sections. Achievable activity versus radionuclidic purity of medically relevant {sup 89}Zr is discussed and compared with the production via the {sup 89}Y(p,n) reaction. Parallel use of titanium and aluminium beam monitors revealed systematic difference between the recommended cross-sections of both monitoring reactions and provided new cross-section data for formation of {sup 24}Na, {sup 27}Mg, {sup 43}Sc, {sup 44m}Sc, {sup 44}Sc, {sup 46}Sc, {sup 47}Sc and {sup 48}Sc. The cross-sections for the {sup nat}Ti(d,x){sup 46}Sc reactions agree very well with recently proposed recommended values.

  10. 宫内节育器避孕效果分析及不良反应监测%Analysis of Contraceptive Effect and Adverse Reaction Monitoring of Intrauterine Device



    ObjectiveTo observe the effect and adverse reaction of intrauterine device.Methods Chose 205 women with intrauterine device,analyzed their contraceptive effect and adverse reaction. Results 205 cases of women,including 14 cases(6.83%)with the pregnancy,adverse reactions included infection,abnormal vaginal discharge,intrauterine device down and abnormal menstruation.Conclusion We should choose the appropriate contraceptive device according to the individual differences,and regularly monitor to improve the contraceptive effect and reduce adverse reaction rate.%目的:观察宫内节育器的避孕效果及不良反应。方法选择205例行宫内节育器妇女的临床资料,分析其避孕效果及不良反应。结果205例女性,其中14例(6.83%)带器妊娠;不良反应主要包括感染、白带异常、宫内节育器下移及月经异常等。结论应根据个体化差异选择合适的节育器,并定期监测以提高避孕效果,降低不良反应率。

  11. Real-time air monitoring of mustard gas and Lewisite 1 by detecting their in-line reaction products by atmospheric pressure chemical ionization ion trap tandem mass spectrometry with counterflow ion introduction.

    Okumura, Akihiko; Takada, Yasuaki; Watanabe, Susumu; Hashimoto, Hiroaki; Ezawa, Naoya; Seto, Yasuo; Sekiguchi, Hiroshi; Maruko, Hisashi; Takayama, Yasuo; Sekioka, Ryoji; Yamaguchi, Shintaro; Kishi, Shintaro; Satoh, Takafumi; Kondo, Tomohide; Nagashima, Hisayuki; Nagoya, Tomoki


    A new method enabling sensitive real-time air monitoring of highly reactive chemical warfare agents, namely, mustard gas (HD) and Lewisite 1 (L1), by detecting ions of their in-line reaction products instead of intact agents, is proposed. The method is based on corona discharge-initiated atmospheric pressure chemical ionization coupled with ion trap tandem mass spectrometry (MS(n)) via counterflow ion introduction. Therefore, it allows for highly sensitive and specific real-time detection of a broad range of airborne compounds. In-line chemical reactions, ionization reactions, and ion fragmentations of these agents were investigated. Mustard gas is oxygenated in small quantity by reactive oxygen species generated in the corona discharge. With increasing air humidity, the MS(2) signal intensity of protonated molecules of mono-oxygenated HD decreases but exceeds that of dominantly existing intact HD. This result can be explained in view of proton affinity. Lewisite 1 is hydrolyzed and oxidized. As the humidity increases from zero, the signal of the final product, namely, didechlorinated, dihydroxylated, and mono-oxygenated L1, quickly increases and reaches a plateau, giving the highest MS(2) and MS(3) signals among those of L1 and its reaction products. The addition of minimal moisture gives the highest signal intensity, even under low humidity. The method was demonstrated to provide sufficient analytical performance to meet the requirements concerning hygienic management and counter-terrorism. It will be the first practical method, in view of sensitivity and specificity, for real-time air monitoring of HD and L1 without sample pretreatment.

  12. 基于MRM的小鼠脑模板创建的研究进展%Recent Advances in the Research of the Establishment of the MRM-based Mouse Brain Template

    付振荣; 林岚; 张柏雯; 宾光宇; 高宏建; 吴水才


    The high resolution magnetic resource microcopy(MRM)has been widely used in mouse brain neuroimaging study. The mouth brain template and atlas are the tools essential to the mouse brain neuroimaging study. The mouth brain is characterized by its small volume and subtle microscopic changes, which creates dififculty for the establishment of the brain template and atlas. Nowadays many domestic and overseas’ researchers have focused on setting up different kinds of mouse brain templates. This paper ifrst introduced the imaging principle and imaging collection methods of MRM and discussed the strategies to optimize MRM. Secondly, the paper discussed basic elements of the mouse brain template construction, such as comparison of templates, data acquisition, registration algorithms, andetc. Finally, the paper introduced the fundamental application of the mouse brain template in the research and treatment of diseases such as Alzheimer’s disease and Huntington’s disease.%高分辨率的磁共振显微成像(MRM)技术已被广泛应用于小鼠脑神经影像学的研究之中。脑模板和脑图谱是小鼠脑神经影像学研究中不可缺少的工具,但由于小鼠大脑具有体积小、微观变化细微等特点,为脑膜板和脑图谱的建立增加了很大的困难,当今国内外大量研究都致力于如何能更好的建立不同类型的小鼠脑模板。本文首先介绍了MRM的成像原理及图像的采集方式,探讨了MRM的优化措施。之后讨论了脑模板构建过程中的一些基本元素,如模板比较、配准算法等。最后介绍了小鼠脑模板在一些脑部疾病(如阿尔茨海默病、亨廷顿氏综合症等)动物模型上的基本应用。


    The paper describes a method of analyzing the production of mycotoxins at the genetic level by monitoring the intracellular levels of messenger RNA (mRNA). Initial work will focus on threshing out the mycotoxin gene clusters in Stachybotrys chartarum followed by analysis of toxin...


    The paper describes a method of analyzing the production of mycotoxins at the genetic level by monitoring the intracellular levels of messenger RNA (mRNA). Initial work will focus on threshing out the mycotoxin gene clusters in Stachybotrys chartarum followed by analysis of toxin...

  15. Modeler软件及其在药品不良反应监测中的应用%Modeler and Discussion on Application of Adverse Drug Reaction Monitoring

    王玲; 陈中; 陈安


    提供了一种技术方法,为药品不良反应监测工作提供参考.利用Modeler软件,通过利用数据挖掘技术的定性分析方法,对药品不良反应病例报告进行处理、分析.数据挖掘的定量分析方法为药品不良反应监测工作提供了一项有益的尝试.%This article provides a technical method for ADR monitoring.By using qualitative analysis of Data Mining technique, ADR case reports were processed and analyzed by using Modeler.The qualitative analysis of data mining method is a useful attempt for ADR monitoring.y

  16. Stable isotope-assisted LC-MS/MS monitoring of glyceryl trinitrate bioactivation in a cell culture model of nitrate tolerance.

    Axton, Elizabeth R; Hardardt, Elizabeth A; Stevens, Jan F


    The nitric oxide (NO) metabolites nitrite (NO2(-)) and nitrate (NO3(-)) can be quantified as an endpoint of endothelial function. We developed a LC-MS/MS method of measuring nitrite and nitrate isotopologues, which has a lower limit of quantification (LLOQ) of 1 nM. This method allows for isotopic labeling to differentiate newly formed nitrite and nitrate from nanomolar to micromolar background levels of nitrite and nitrate in biological matrices. This method utilizes 2,3-diaminonaphthalene (DAN) derivatization, which reacts with nitrite under acidic conditions to produce 2,3-naphthotriazole (NAT). NAT was chromatographically separated on a Shimadzu LC System with an Agilent Extend-C18 5 μm 2.1 × 150 mm column and detected using a multiple reaction monitoring (MRM) method on an ABSciex 3200 QTRAP mass spectrometer operated in positive mode. Mass spectrometry allows for the quantification of (14)N-NAT (m/z 170.1) and (15)N-NAT (m/z 171.1). Both nitrite and nitrate demonstrated a linear detector response (1 nM - 10 μM, 1 nM - 100 nM, respectively), and were unaffected by common interferences (Dulbecco's Modified Eagle Medium (DMEM), fetal bovine serum (FBS), phenol red, and NADPH). This method requires minimal sample preparation, making it ideal for most biological applications. We applied this method to develop a cell culture model to study the development of nitrate tolerance in human endothelial cells (EA.hy926).

  17. Validation of the concentration profiles obtained from the near infrared/multivariate curve resolution monitoring of reactions of epoxy resins using high performance liquid chromatography as a reference method.

    Garrido, M; Larrechi, M S; Rius, F X


    This paper reports the validation of the results obtained by combining near infrared spectroscopy and multivariate curve resolution-alternating least squares (MCR-ALS) and using high performance liquid chromatography as a reference method, for the model reaction of phenylglycidylether (PGE) and aniline. The results are obtained as concentration profiles over the reaction time. The trueness of the proposed method has been evaluated in terms of lack of bias. The joint test for the intercept and the slope showed that there were no significant differences between the profiles calculated spectroscopically and the ones obtained experimentally by means of the chromatographic reference method at an overall level of confidence of 5%. The uncertainty of the results was estimated by using information derived from the process of assessment of trueness. Such operational aspects as the cost and availability of instrumentation and the length and cost of the analysis were evaluated. The method proposed is a good way of monitoring the reactions of epoxy resins, and it adequately shows how the species concentration varies over time.

  18. Experimental verification of proton beam monitoring in a human body by use of activity image of positron-emitting nuclei generated by nuclear fragmentation reaction.

    Nishio, Teiji; Miyatake, Aya; Inoue, Kazumasa; Gomi-Miyagishi, Tomoko; Kohno, Ryosuke; Kameoka, Satoru; Nakagawa, Keiichi; Ogino, Takashi


    Proton therapy is a form of radiotherapy that enables concentration of dose on a tumor by use of a scanned or modulated Bragg peak. Therefore, it is very important to evaluate the proton-irradiated volume accurately. The proton-irradiated volume can be confirmed by detection of pair-annihilation gamma rays from positron-emitting nuclei generated by the nuclear fragmentation reaction of the incident protons on target nuclei using a PET apparatus. The activity of the positron-emitting nuclei generated in a patient was measured with a PET-CT apparatus after proton beam irradiation of the patient. Activity measurement was performed in patients with tumors of the brain, head and neck, liver, lungs, and sacrum. The 3-D PET image obtained on the CT image showed the visual correspondence with the irradiation area of the proton beam. Moreover, it was confirmed that there were differences in the strength of activity from the PET-CT images obtained at each irradiation site. The values of activity obtained from both measurement and calculation based on the reaction cross section were compared, and it was confirmed that the intensity and the distribution of the activity changed with the start time of the PET imaging after proton beam irradiation. The clinical use of this information about the positron-emitting nuclei will be important for promoting proton treatment with higher accuracy in the future.

  19. Bioimaging for the monitoring of the in vivo distribution of infused mesenchymal stem cells in a mouse model of the graft-versus-host reaction.

    Joo, Sun-Young; Cho, Kyung-Ah; Jung, Yun-Jae; Kim, Han-seong; Park, Seong-Yeol; Choi, Yong-Bock; Hong, Kyung-man; Woo, So-Youn; Seoh, Ju-Young; Ryu, Kyung-Ha


    Cell therapy using MSCs (mesenchymal stem cells) might be effective treatment for refractory GVHD (graft-versus-host disease). However, the fate and distribution of MSCs after transplantation remains unclear. In this study, an animal model was developed to monitor the dynamic distribution of MSCs in mice with GVHD. A GVHD mouse model was established by transplanting C57BL/6 donor bone marrow cells and C57BL/6 EGFP (enhanced green fluorescent protein) splenocytes into lethally irradiated BALB/c nude recipient mice. Donor MSCs were obtained from MHC-identical C57BL/6 RFP (red fluorescent protein) mice and infused into the recipient mice on the same transplantation day. In vivo movement of the donor splenocytes (EGFP) and MSCs (RFP) were evaluated by measuring the biofluorescence (IVIS-Xenogen system). Donor splenocytes and MSCs reached the lungs first, and then the gastrointestinal tract, lymph nodes and skin, in that order; the transit time and localization site of these cells were very similar. In the recipient mouse with GVHD, the number of detectable cells declined with time, as assessed by biofluorescence imaging and confirmed by RT (real-time)-PCR. This bioimaging system might be useful for preclinical testing and the design of therapeutic strategies for monitoring the dynamic distribution of MSCs with GVHD.

  20. Evolving factor analysis-based method for correcting monitoring delay in different batch runs for use with PLS: On-line monitoring of a transesterification reaction by ATR-FTIR.

    Trevisan, Marcello G; Garcia, Camila M; Schuchardt, Ulf; Poppi, Ronei J


    In this work, the base-catalyzed transesterification of soybean oil with ethanol was monitored on-line using mid-infrared spectroscopy (MIRS) and the yield of fatty acid ethyl esters (biodiesel) was obtained by (1)H NMR spectroscopy. The MIRS monitoring carried out for 12min, was performed using a cylindrical internal reflectance cell of PbSe in the range of 3707-814cm(-1) with eight co-added scans. Two different data treatment strategies were used: in the first, the models were built using the raw data and in the other, evolving factor analysis (EFA) was used to overcome the sensor time delay due to the on-line analysis, producing significantly better results. In addition, models based on partial least squares (PLS) using three batches for calibration and another for validation were compared with models with just one batch for calibration and three for validation. The models were compared between each other using root mean square error of prediction (RMSEP) and root mean square prediction difference (RMSPD), obtaining relative errors under 3%.

  1. Combining self-modeling curve resolution methods and partial least squares to develop a quantitative reaction monitoring method with minimal reference data.

    Pedge, Nicholas I; Walmsley, Anthony D


    An example of combining self-modeling curve resolution (SMCR) methods and partial least squares (PLS) to construct a quantitative model using minimal reference data is presented. The objective was to construct a quantitative calibration model to allow real-time in situ ultraviolet-attenuated total reflection (UV/ATR) measurements to determine the end-point during a chlorination reaction. Time restrictions for development combined with difficult reaction sampling conditions required the method to be developed using only a few key reference measurements. Utilizing evolving factor analysis (EFA) and the orthogonal projection approach (OPA), initial estimates of the concentration and spectral profiles for the intermediate and product were obtained. Further optimization by multivariate curve resolution-alternating least squares (MCR-ALS) led to refined estimates of the concentration profiles. A PLS2 model was then constructed using the calculated concentration profiles and the preprocessed UV spectra. Using a standard PLS model compatible with the spectrometer's standard process software facilitated real-time predictions for new batches. This method was applied to five 45 liter batches in a large-scale laboratory facility. The method successfully predicted the product concentration of batch 1 but exhibited larger prediction error for subsequent batches. The largest prediction error was attained during batch 3, for which a final concentration of 0.22 mole L(-1) was predicted, while the true measured value was 0.271 mole L(-1) (an error of 18.8%). However, the qualitative real-time profiles proved to be extremely useful as they allowed the end-point to be determined without sampling or performing off-line analysis. Furthermore, the concentration profile of the intermediate species, which could not be observed by the offline method, could also be observed in real-time and gave further confidence that the process was approaching the end-point. Another benefit of real

  2. In operando x-ray tomography for next-generation batteries: a systematic approach to monitor reaction product distribution and transport processes

    Schröder, D.; Bender, C. L.; Arlt, T.; Osenberg, M.; Hilger, A.; Risse, S.; Ballauff, M.; Manke, I.; Janek, J.


    Computed tomography with x-rays is a powerful tool to analyze the complex reaction and transport processes that occur inside electrochemical storage devices. To this day, a better insight into the occurring processes is needed and will yield improvements in energy density and cycling stability of next-generation batteries. Herein we present general considerations for the use of x-ray tomography of batteries to gain a detailed insight during operation. Furthermore, we present examples for the tomography of zinc-oxygen batteries, sodium-oxygen batteries and metal-sulfur batteries, elucidating performance limiting degradation processes such as dendrite formation and loss of liquid electrolyte. With the method applied, we aim to establish an effective link between the battery and x-ray community by offering a guideline on how to apply x-ray tomography to propel research on battery materials and entire batteries.

  3. The Role of Left Hemispheric Structures for Emotional Processing as a Monitor of Bodily Reaction and Felt Chill – a Case-Control Functional Imaging Study

    Grunkina, Viktoria; Holtz, Katharina; Klepzig, Kai; Neubert, Jörg; Horn, Ulrike; Domin, Martin; Hamm, Alfons O.; Lotze, Martin


    Background: The particular function of the left anterior human insula on emotional arousal has been illustrated with several case studies. Only after left hemispheric insula lesions, patients lose their pleasure in habits such as listening to joyful music. In functional magnetic resonance imaging studies (fMRI) activation in the left anterior insula has been associated with both processing of emotional valence and arousal. Tight interactions with different areas of the prefrontal cortex are involved in bodily response monitoring and cognitive appraisal of a given stimulus. Therefore, a large left hemispheric lesion including the left insula should impair the bodily response of chill experience (objective chill response) but leave the cognitive aspects of chill processing (subjective chill response) unaffected. Methods: We investigated a patient (MC) with a complete left hemispheric media cerebral artery stroke, testing fMRI representation of pleasant (music) and unpleasant (harsh sounds) chill response. Results: Although chill response to both pleasant and unpleasant rated sounds was confirmed verbally at passages also rated as chilling by healthy participants, skin conductance response was almost absent in MC. For a healthy control (HC) objective and subjective chill response was positively associated. Bilateral prefrontal fMRI-response to chill stimuli was sustained in MC whereas insula activation restricted to the right hemisphere. Diffusion imaging together with lesion maps revealed that left lateral tracts were completely damaged but medial prefrontal structures were intact. Conclusion: With this case study we demonstrate how bodily response and cognitive appraisal are differentially participating in the internal monitor of chill response. PMID:28111546

  4. A Selected Reaction Monitoring (SRM)-Based Method for Absolute Quantification of Aβ38, Aβ40, and Aβ42 in Cerebrospinal Fluid of Alzheimer's Disease Patients and Healthy Controls

    Pannee, Josef; Portelius, Erik; Oppermann, Madalina


    Cerebrospinal fluid (CSF) biomarkers for Alzheimer's disease (AD) are increasingly used in research centers, clinical trials, and clinical settings. However, their broad-scale use is hampered by lack of standardization across analytical platforms and by interference from binding of amyloid-β (Aβ......) to matrix proteins as well as self-aggregation. Here, we report on a matrix effect-resistant method for the measurement of the AD-associated 42 amino acid species of Aβ (Aβ42), together with Aβ40 and Aβ38 in human CSF based on mass spectrometric quantification using selected reaction monitoring (SRM...... with mild to moderate dementia. Analytical characteristics of the method include a lower limit of quantification of 62.5 pg/mL for Aβ42 and coefficients of variations below 10%. In a pilot study on AD patients and controls, we verified disease-association with decreased levels of Aβ42 similar...

  5. Use of ubiquitous, highly heterozygous copy number variants and digital droplet polymerase chain reaction to monitor chimerism after allogeneic haematopoietic stem cell transplantation.

    Whitlam, John B; Ling, Ling; Swain, Michael; Harrington, Tom; Mirochnik, Oksana; Brooks, Ian; Cronin, Sara; Challis, Jackie; Petrovic, Vida; Bruno, Damien L; Mechinaud, Francoise; Conyers, Rachel; Slater, Howard


    Chimerism analysis has an important role in the management of allogeneic hematopoietic stem cell transplantation. It informs response to disease relapse, graft rejection, and graft-versus-host disease. We have developed a method for chimerism analysis using ubiquitous copy number variation (CNV), which has the benefit of a "negative background" against which multiple independent informative markers are quantified using digital droplet polymerase chain reaction. A panel of up to 38 CNV markers with homozygous deletion frequencies of approximately 0.4-0.6 were used. Sensitivity, precision, reproducibility, and informativity were assessed. CNV chimerism results were compared against established fluorescence in situ hybridization, single nucleotide polymorphism, and short tandem repeat-based methods with excellent correlation. Using 30 ng of input DNA per well, the limit of detection was 0.05% chimerism and the limit of quantification was 0.5% chimerism. High informativity was seen with a median of four informative markers detectable per individual in 39 recipients and 43 donor genomes studied. The strength of this approach was exemplified in a multiple donor case involving four genomes (three related). The precision, sensitivity, and informativity of this approach recommend it for use in clinical practice.

  6. Capillary Electrophoresis-nanoelectrospray Ionization-selected Reaction Monitoring Mass Spectrometry Via A True Sheathless Metal-coated Emitter Interface For Robust And High Sensitivity Sample Quantification

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


    A new sheathless CITP/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 electro chemical reaction at the emitter tip or inside of 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 bellow 5 attomole.

  7. High-sensitivity capillary electrophoresis method for monitoring purine nucleoside phosphorylase and adenosine deaminase reactions by a reversed electrode polarity switching mode.

    Iqbal, Jamshed; Müller, Christa E


    A simple, efficient, and highly sensitive in-line CE method was developed for the characterization and for inhibition studies of the nucleoside-metabolizing enzymes purine nucleoside phosphorylase (PNP) and adenosine deaminase (ADA) present in membrane preparations of human 1539 melanoma cells. After filling the running buffer (50 mM borate buffer, 100 mM SDS, pH 9.10) into a fused-silica capillary (50 cm effective length × 75 μm), a large sample volume was loaded by hydrodynamic injection (5 psi, 36 s), followed by the removal of the large plug of sample matrix from the capillary using polarity switching (-20 kV). The current was monitored and the polarity was reversed when 95% of the current had been recovered. The separation of the neutral analytes (nucleosides and nucleobases) was performed by applying a voltage of 15 kV. An about 10-fold improvement of sensitivity for the five investigated analytes (adenosine, inosine, adenine, hypoxanthine, xanthine) was achieved by large-volume stacking with polarity switching when compared with CE without stacking. For inosine and adenine detection limits as low as 60 nM were achieved. To the best of our knowledge, this represents the highest sensitivity for nucleoside and nucleobase analysis using CE with UV detection reported so far. The Michaelis-Menten constants (K(m)) for PNP and ADA and the inhibition constants (K(i)) for standard inhibitors determined with the new method were consistent with literature data.

  8. Self-assembled dopamine nanolayers wrapped carbon nanotubes as carbon-carbon bi-functional nanocatalyst for highly efficient oxygen reduction reaction and antiviral drug monitoring

    Khalafallah, Diab; Akhtar, Naeem; Alothman, Othman Y.; Fouad, H.; Abdelrazek khalil, Khalil


    Oxygen reduction reaction (ORR) catalysts are the heart of eco-friendly energy resources particularly low temperature fuel cells. Although valuable efforts have been devoted to synthesize high performance catalysts for ORR, considerable challenges are extremely desirable in the development of energy technologies. Herein, we report a simple self-polymerization method to build a thin film of dopamine along the tubular nanostructures of multi-walled carbon nanotubes (CNT) in a weak alkaline solution. The dopamine@CNT hybrid (denoted as DA@CNT) reveals an enhanced electrocatalytic activity towards ORR with highly positive onset potential and cathodic current as a result of their outstanding features of longitudinal mesoporous structure, high surface area, and ornamentation of DA layers with nitrogen moieties, which enable fast electron transport and fully exposed electroactive sites. Impressively, the as-obtained hybrid afford remarkable electrochemical durability for prolonged test time of 60,000 s compared to benchmark Pt/C (20 wt%) catalyst. Furthermore, the developed DA@CNT electrode was successfully applied to access the quality of antiviral drug named Valacyclovir (VCR). The DA@CNT electrode shows enhanced sensing performance in terms of large linear range (3-75 nM), low limit of detection (2.55 nM) than CNT based electrode, indicating the effectiveness of the DA coating. Interestingly, the synergetic effect of nanostructured DA and CNT can significantly boost the electronic configuration and exposure level of active species for ORR and biomolecule recognition. Therefore, the existing carbon-based porous electrocatalyst may find numerous translational applications as attractive alternative to noble metals in polymer electrolyte membrane fuel cells and quality control assessment of pharmaceutical and therapeutic drugs.

  9. Hyphenation of Proton Transfer Reaction Mass Spectrometry with Thermal Analysis (TG/PTR-MS) for Monitoring the Thermal Degradation of Retinyl Acetate.

    Peinado, Irene; Mason, Marco; Biasioli, Franco; Scampicchio, Matteo


    The processing of retinyl acetate, a vitamin and biomarker, at high temperatures causes significant decomposition of the compound and thus loss of its activity. The rate of mass loss can be conveniently studied by thermogravimetry (TG). However, this technique generally fails to reveal which compounds have been evolved from the compound. In this work we propose a new hyphenation approach to continuously monitor the thermal decomposition of retinyl acetate and follow the evolution of specific volatile organic compounds (VOCs). Thermal degradation of retinyl acetate was followed by TG coupled to a direct injection mass spectrometer based on proton transfer mass spectrometry (PTR-MS) to follow continuously the thermal decomposition of retinyl acetate. The results were also compared with those obtained by a second evolved gas analysis system based on the coupling of TG with FTIR. The TG results showed two main mass losses, at 180°C and 350°C. When the PTR-MS instrument was connected to the outlet of the TG instrument, specific fragment ions (m/z 43, 61, 75, 85 and 97) showed characteristic evolution profiles. The first mass loss was mainly associated with the release of acetic acid (m/z 43 and 61), whereas the second mass loss was connected with the degradation of the molecule backbone (m/z 43, 61, 75, 85 and 97). These results were substantially correlated with those achieved by TG coupled with FTIR, although PTR-MS showed superior performance in terms of the qualitative identification of specific fragments and better sensitivity toward complex organic VOCs. The proposed TG-PTR-MS technique shows a great potential for following in real time the thermal degradation of ingredients such as retinyl acetate and identifying compounds evolved at specific temperatures. This article is protected by copyright. All rights reserved.

  10. An in-house real-time polymerase chain reaction: standardisation and comparison with the Cobas Amplicor HBV monitor and Cobas AmpliPrep/Cobas TaqMan HBV tests for the quantification of hepatitis B virus DNA

    Santos, Ana Paula de Torres; Levi, José Eduardo; Lemos, Marcilio Figueiredo; Calux, Samira Julien; Oba, Isabel Takano; Moreira, Regina Célia


    This study aimed to standardise an in-house real-time polymerase chain reaction (rtPCR) to allow quantification of hepatitis B virus (HBV) DNA in serum or plasma samples, and to compare this method with two commercial assays, the Cobas Amplicor HBV monitor and the Cobas AmpliPrep/Cobas TaqMan HBV test. Samples from 397 patients from the state of São Paulo were analysed by all three methods. Fifty-two samples were from patients who were human immunodeficiency virus and hepatitis C virus positive, but HBV negative. Genotypes were characterised, and the viral load was measure in each sample. The in-house rtPCR showed an excellent success rate compared with commercial tests; inter-assay and intra-assay coefficients correlated with commercial tests (r = 0.96 and r = 0.913, p < 0.001) and the in-house test showed no genotype-dependent differences in detection and quantification rates. The in-house assay tested in this study could be used for screening and quantifying HBV DNA in order to monitor patients during therapy. PMID:26872342

  11. Surface-crosslinked poly(3-mercaptopropyl)methylsiloxane-coatings on silica as new platform for low-bleed mass spectrometry-compatible functionalized stationary phases synthesized via thiol-ene click reaction.

    Zimmermann, Aleksandra; Horak, Jeannie; Sievers-Engler, Adrian; Sanwald, Corinna; Lindner, Wolfgang; Kramer, Markus; Lämmerhofer, Michael


    A thin functional film of poly(3-mercaptopropyl)methylsiloxane was coated onto vinyl-modified silica particles (5μm, 100Å pore size) and chemically crosslinked to the surface. Excess of thiol functionalities allow bonding of alkene containing ligands by thiol-ene click reaction in a second step (QN-VII). Besides that a single step surface modification procedure was established in which alkene functional ligands were directly added to the polysiloxane coating solution and thus, after evaporation of the solvent, crosslinking to the vinylized surface and bonding of chromatographic ligand to the thiolated polysiloxane film occur simultaneously in one step (QN-VI). Successful bonding of the polysiloxane film was confirmed for both approaches by (29)Si cross-polarization/magic angle spinning NMR spectra. The new surface functionalization concept can be utilized as a new platform for the preparation of various low-bleed, mass spectrometry-compatible stationary phases with a variety of functional ligands. The concept was demonstrated by thiol-ene click reaction with quinine carbamate and its subsequent use for enantiomer separation by HPLC-UV and HPLC-ESI-QTOF-MS of acidic chiral analytes. Chromatographic enantioselectivities were similar to a comparable brush-type CSP (QN-V0). The greatly reduced background signal in LC-MS, however, comes at expense of somewhat lower chromatographic efficiencies (C-term by factor of 2 larger compared to brush-type CSP). For quantitative analysis in single reaction monitoring (MRM(HR)) in high sensitivity mode, limit of detection and limit of quantification results are comparable for both surface-polymer modified CSPs, with only slightly higher values for the conventional brush-type CSP (QN-V0). Copyright © 2016 Elsevier B.V. All rights reserved.


    陈立群; 邵丽文; 江爱玉


    Objective To discuss the effect of three -level monitoring to reduce the abnormal reaction incidence rate after bacillus calmette - guerin( BCG ) vaccination. Methods A total of 4 346 cases of newborn who were born in 2009 were assigned into control group ,3 999 cases of newborn born in 2010 into experimental group. Experimental group was given three-level monitoring on response after BCG vaccination and control group was observed traditionaly after the BCG vaccinaLion. The abnormal reaction incidence rate after BCG vaccination and the parents' satisfaction of BCG vaccination work were observed. Results The abnormal reactions of experimental group occurred at a rate of 1.50 per thousand, and the control group was 3.91 per thousand, the difference was statistically significant( P < 0. 05 ). The satisfaction of parents at discharge in experimental group was 96. 17% and control group was 94. 22% ; When the babies were six months old the satisfacLion of parenLs in experimental group was 91. 42% and control group was 88.47% with a significant difference( P<0.05 ). Conclusion Implementation of the three-level monitoring reduces the abnormal reaction incidence rate after vaccination, improves the parenLs'satisfaction with BCG vaccination work.%目的 探讨三级监控降低卡介苗接种后异常反应发生率的效果.方法 以2009年出生的新生儿4 346例为对照组,2010年出生的3 999例为试验组.试验组实施卡介苗接种后反应的三级监控,对照组采用传统的卡介苗接种后的观察.观察2组卡介苗接种后异常反应发生率及家长对卡介苗接种工作满意度.结果 试验组的异常反应发生率为1.50‰,对照组发生率为3.91‰,差异有统计学意义(P>0.05).出院时家长满意度试验组为96.17%,对照组为94.22%,婴儿6个月时满意度试验组为91.42%,对照组为88.47%,差异有统计学意义(P<0.01).结论 实施三级监控降低了接种后异常反应发生率,提高了家长对卡介苗预防接种工作的满意度.

  13. Correlation between y-Type Ions Observed in Ion Trap and Triple Quadrupole Mass Spectrometers

    Sherwood, Carly A.; Eastham, Ashley; Lee, Lik Wee; Risler, Jenni; Vitek, Olga; Martin, Daniel B.


    Multiple reaction monitoring mass spectrometry (MRM-MS) is a technique for high-sensitivity targeted analysis. In proteomics, MRM-MS can be used to monitor and quantify a peptide based on the production of expected fragment peaks from the selected peptide precursor ion. The choice of which fragment ions to monitor in order to achieve maximum sensitivity in MRM-MS can potentially be guided by existing MS/MS spectra. However, because the majority of discovery experiments are performed on ion tr...

  14. Application of infrared thermography in FCC reaction regeneration system monitoring%应用红外热像技术监测催化装置反再系统

    高建苹; 张建平; 梁学福; 柏海见


    The use of infrared thermography technology in Lanzhou Petrochemical Industries Co of the 1400000 ton/ year catalytic device for reaction-reproduction system monitoring, through the detection data to judge the heat equipment lining damage cases, judges the device part position of defect damage, if the process control of a slight negligence, with cases a serious accident. Through this special inspection, as a device to provide a scientific basis for safe operation. Through the application of non-destructive testing technology of key parts, executive key monitoring, safeguard the normal running of the device,to meet the needs of production and operation of the plant.%利用红外热像技术对兰州石化公司140万吨/年催化装置反再系统进行监测,通过检测数据判断热设备衬里损伤情况,经判断该套装置部分位置出现缺陷损伤,如果工艺控制稍有疏忽,会导致严重事故.通过本次特护检测,为装置的安全运行提供科学的参考依据.通过无损检测技术的应用,对重点部位实施重点监测,保障装置的正常运行,满足装置生产运行的需求.

  15. Reaction Graph



    The paper proposes reaction graphs as graphical representations of computational objects.A reaction graph is a directed graph with all its arrows and some of its nodes labeled.Computations are modled by graph rewriting of a simple nature.The basic rewriting rules embody the essence of both the communications among processes and cut-eliminations in proofs.Calculi of graphs are ideentified to give a formal and algebraic account of reaction graphs in the spirit of process algebra.With the help of the calculi,it is demonstrated that reaction graphs capture many interesting aspects of computations.

  16. Exposure to anti-malarial drugs and monitoring of adverse drug reactions using toll-free mobile phone calls in private retail sector in Sagamu, Nigeria: implications for pharmacovigilance

    Ogunwande Isiaka A


    Full Text Available Abstract Background Adverse drug reactions (ADRs contribute to ill-health or life-threatening outcomes of therapy during management of infectious diseases. The exposure to anti-malarial and use of mobile phone technology to report ADRs following drug exposures were investigated in Sagamu - a peri-urban community in Southwest Nigeria. Methods Purchase of medicines was actively monitored for 28 days in three Community Pharmacies (CP and four Patent and Proprietary Medicine Stores (PPMS in the community. Information on experience of ADRs was obtained by telephone from 100 volunteers who purchased anti-malarials during the 28-day period. Results and Discussion A total of 12,093 purchases were recorded during the period. Antibiotics, analgesics, vitamins and anti-malarials were the most frequently purchased medicines. A total of 1,500 complete courses of anti-malarials were purchased (12.4% of total purchases; of this number, purchases of sulphadoxine-pyrimethamine (SP and chloroquine (CQ were highest (39.3 and 25.2% respectiuvely. Other anti-malarials purchased were artesunate monotherapy (AS - 16.1%, artemether-lumefantrine (AL 10.0%, amodiaquine (AQ - 6.6%, quinine (QNN - 1.9%, halofantrine (HF - 0.2% and proguanil (PR - 0.2%. CQ was the cheapest (USD 0.3 and halofantrine the most expensive (USD 7.7. AL was 15.6 times ($4.68 more expensive than CQ. The response to mobile phone monitoring of ADRs was 57% in the first 24 hours (day 1 after purchase and decreased to 33% by day 4. Participants in this monitoring exercise were mostly with low level of education (54%. Conclusion The findings from this study indicate that ineffective anti-malaria medicines including monotherapies remain widely available and are frequently purchased in the study area. Cost may be a factor in the continued use of ineffective monotherapies. Availability of a toll-free telephone line may facilitate pharmacovigilance and follow up of response to medicines in a resource

  17. Simultaneous qualitative and quantitative method using liquid chromatography selected reaction monitoring-triggered quantitation-enhanced data-dependent tandem mass spectrometry for the identification and classification of amphetamine-type stimulant abusers in human urine.

    Lee, Sang Kyu; Kim, So-Hee; Kim, Ho Jun; Yoo, Hye Hyun; Kwon, Oh Seung; In, Moon Kyo; Jin, Changbae; Kim, Dong Hyun; Lee, Jaeick


    Amphetamine (AP) and amphetamine-type stimulants, methamphetamine (MA) and N,N-dimethylamphetamine (DMA), are known as central nervous system stimulants, and their abuse throughout the world has recently increased. Since it is difficult to physically distinguish among AP, MA and DMA, analysts may not be aware of what abusers have administered. In this study, following the detection of specific metabolites of AP, MA and DMA as biomarkers in abuser urines, a rapid and sensitive method was developed for the identification and classification of AP-type stimulants abusers. After the simple filtration of the urine samples, the samples were directly analyzed using a liquid chromatography/tandem mass spectrometry system with selected reaction monitoring (SRM)-triggered quantitation-enhanced data-dependent MS/MS (QED-MS/MS) for the simultaneous qualitative and quantitative analysis of p-hydroxy AP, p-hydroxy MA, p-hydroxy DMA, AP, MA, DMA and DMA N-oxide. The determination of p-hydroxy AP, p-hydroxy MA, AP, MA, DMA and DMA N-oxide was accurate and reproducible, with the limits of quantitation of 5 ng/mL in urine. When applied to the urine samples of suspected AP-type stimulants abusers, the abused drugs were precisely identified between MA and DMA abusers.

  18. Reaction Order Ambiguity in Integrated Rate Plots

    Lee, Joe


    Integrated rate plots are frequently used in reaction kinetics to determine orders of reactions. It is often emphasised, when using this methodology in practice, that it is necessary to monitor the reaction to a substantial fraction of completion for these plots to yield unambiguous orders. The present article gives a theoretical and statistical…

  19. Quantitative analysis of UV-A shock and short term stress using iTRAQ, pseudo selective reaction monitoring (pSRM) and GC-MS based metabolite analysis of the cyanobacterium Nostoc punctiforme ATCC 29133.

    Wase, Nishikant; Pham, Trong Khoa; Ow, Saw Yen; Wright, Phillip C


    A quantitative proteomics and metabolomics analysis was performed using iTRAQ, HPLC and GC-MS in the filamentous cyanobacterium Nostoc punctiforme ATCC 29133 to understand the effect of short and long term UV-A exposure. Changes in the proteome were measured for short-term stress (4-24h) using iTRAQ. Changes in the photosynthetic pigments and intracellular metabolites were observed at exposures of up to 7days (pigments) and up to 11days (intracellular metabolites). To assess iTRAQ measurement quality, pseudo selected reaction monitoring (pSRM) was used, with this confirming underestimation of protein abundance levels by iTRAQ. Our results suggest that short term UV-A radiation lowers the abundance of PS-I and PS-II proteins. We also observed an increase in abundance of intracellular redox homeostasis proteins and plastocyanin. Additionally, we observed statistically significant changes in scytonemin, Chlorophyll A, astaxanthin, zeaxanthin, and β-carotene. Assessment of intracellular metabolites showed significant changes in several, suggesting their potential role in the Nostoc's stress mitigation strategy. Cyanobacteria under UV-A radiation have reduced growth due to intensive damage to essential functions, but the organism shows a defense response by remodeling bioenergetics pathway, induction of the UV protection compound scytonemin and increased levels of proline and tyrosine as a mitigation response. The effect of UV-A radiation on the proteome and intracellular metabolites of N. punctiforme ATCC 29133 including photosynthetic pigments has been described. We also verify the expression of 13 iTRAQ quantified protein using LC-pSRM. Overall we observed that UV-A radiation has a drastic effect on the photosynthetic machinery, photosynthetic pigments and intracellular amino acids. As a mitigation strategy against UV-A radiation, proline, glycine, and tyrosine were accumulated. Copyright © 2014. Published by Elsevier B.V.

  20. Sensitive and rapid method for amino acid quantitation in malaria biological samples using AccQ.Tag ultra performance liquid chromatography-electrospray ionization-MS/MS with multiple reaction monitoring.

    Armenta, Jenny M; Cortes, Diego F; Pisciotta, John M; Shuman, Joel L; Blakeslee, Kenneth; Rasoloson, Dominique; Ogunbiyi, Oluwatosin; Sullivan, David J; Shulaev, Vladimir


    An AccQ*Tag ultra performance liquid chromatography-electrospray ionization-tandem mass spectrometry (AccQ*Tag-UPLC-ESI-MS/MS) method for fast, reproducible, and sensitive amino acid quantitation in biological samples, particularly, the malaria parasite Plasmodium falciparum is presented. The Waters Acquity TQD UPLC/MS system equipped with a photodiode array (PDA) detector was used for amino acid separation and detection. The method was developed and validated using amino acid standard mixtures containing acidic, neutral, and basic amino acids. For MS analysis, the optimum cone voltage implemented, based on direct infusion analysis of a few selected AccQ*Tag amino acids with multiple reaction monitoring, varied from 29 to 39 V, whereas the collision energy varied from 15 to 35 V. Calibration curves were built using both internal and external standardization. Typically, a linear response for all amino acids was observed at concentration ranges of 3 x 10(-3)-25 pmol/muL. For some amino acids, concentration limits of detection were as low as 1.65 fmol. The coefficients of variation for retention times were within the range of 0.08-1.08%. The coefficients of variation for amino acid quantitation, determined from triplicate UPLC-MS/MS runs, were below 8% on the average. The developed AccQ*Tag-UPLC-ESI-MS/MS method revealed good technical and biological reproducibility when applied to P. falciparum and human red blood cells samples. This study should provide a valuable insight into the performance of UPLC-ESI-MS/MS for amino acid quantitation using AccQ*Tag derivatization.

  1. Kinetics of onset of mouse sperm acrosome reaction induced by solubilized zona pellucida: fluorimetric determination of loss of pH gradient between acrosomal lumen and medium monitored by dapoxyl (2-aminoethyl) sulfonamide and of intracellular Ca(2+) changes monitored by fluo-3.

    Rockwell, P L; Storey, B T


    The onset of the zona pellucida-induced acrosome reaction in mouse sperm is marked by loss of the pH gradient existing in acrosome-intact sperm between the acidic acrosomal lumen and the suspending medium, due to pore formation between outer acrosomal and plasma membranes. In earlier work, it was shown that this pH gradient loss occurred in single sperm bound to structurally intact zonae pellucidae with a half-time of 2.1 min; the extended kinetics of this loss determined in a sperm population bound to intact zonae was due to a 180-min range of variable lag times. We hypothesized that this lag time range was due to steric constraints imposed by the three-dimensional structure of the structurally intact zona pellucida, and that this constraint should be removed in solubilized zonae. The fluorescent probe, Dapoxyl(TM) (2-aminoethyl)sulfonamide (DAES) allowed a test of this hypothesis in a population of sperm cells. It is a weak base that is non-fluorescent in aqueous solution, but which accumulates in the acidic acrosomal compartment due to the pH gradient with highly enhanced fluorescence; loss of the pH gradient leads to a decrease in fluorescence. The half-time for DAES fluorescence loss in a population of capacitated, acrosome-intact sperm in response to solubilized zona pellucida protein was 2.13 +/- 0.10 min (SEM, n = 9). The agreement between single cell and cell population kinetics validates the hypothesis of steric constraint in the structurally intact zona pellucida. The change in intracellular Ca(2+) concentration in response to solubilized zona pellucida, as monitored with fluo-3, was a rapid increase, followed by a decrease, with a half-time of 0.85 +/- 0.09 min (SEM, n = 6) to a steady state level higher than the initial level, indicating this Ca(2+) transient as the precursor reaction to onset of the zona-induced acrosome reaction. Copyright 2000 Wiley-Liss, Inc.

  2. A one-year monitoring of nicotine use in sport: frontier between potential performance enhancement and addiction issues.

    Marclay, François; Grata, Elia; Perrenoud, Laurent; Saugy, Martial


    Tobacco consumption is a global epidemic responsible for a vast burden of disease. With pharmacological properties sought-after by consumers and responsible for addiction issues, nicotine is the main reason of this phenomenon. Accordingly, smokeless tobacco products are of growing popularity in sport owing to potential performance enhancing properties and absence of adverse effects on the respiratory system. Nevertheless, nicotine does not appear on the 2011 World Anti-Doping Agency (WADA) Prohibited List or Monitoring Program by lack of a comprehensive large-scale prevalence survey. Thus, this work describes a one-year monitoring study on urine specimens from professional athletes of different disciplines covering 2010 and 2011. A method for the detection and quantification of nicotine, its major metabolites (cotinine, trans-3-hydroxycotinine, nicotine-N'-oxide and cotinine-N-oxide) and minor tobacco alkaloids (anabasine, anatabine and nornicotine) was developed, relying on ultra-high pressure liquid chromatography coupled to triple quadrupole mass spectrometry (UHPLC-TQ-MS/MS). A simple and fast dilute-and-shoot sample treatment was performed, followed by hydrophilic interaction chromatography-tandem mass spectrometry (HILIC-MS/MS) operated in positive electrospray ionization (ESI) mode with multiple reaction monitoring (MRM) data acquisition. After method validation, assessing the prevalence of nicotine consumption in sport involved analysis of 2185 urine samples, accounting for 43 different sports. Concentrations distribution of major nicotine metabolites, minor nicotine metabolites and tobacco alkaloids ranged from 10 (LLOQ) to 32,223, 6670 and 538 ng/mL, respectively. Compounds of interest were detected in trace levels in 23.0% of urine specimens, with concentration levels corresponding to an exposure within the last three days for 18.3% of samples. Likewise, hypothesizing conservative concentration limits for active nicotine consumption prior and/or during

  3. Capture reactions

    Endt, P.M.


    Capture reactions will be considered here from the viewpoint of the nuclear spectroscopist. Especially important to him are the capture of neutrons, protons, and alpha particles, which may proceed through narrow resonances, offering a well defined initial state for the subsequent deexcitation proces

  4. Allergic Reactions

    ... round, they may be caused by exposure to indoor allergens such as dust mites, indoor molds or pets. Urticaria, or hives, is characterized ... home. Video: What is an allergic reaction? » Utility navigation Donate Annual meeting Browse your conditions Check pollen ...

  5. Analysis and Prospect of the Present Situation of Grassroots Level Adverse Drug Reaction Monitoring System Construction in Our Country%我国基层药品不良反应监测体系建设现状分析及展望

    金锋; 曲毅; 樊若曦; 李馨龄


    Objective Through analyzing researches on the current status of the grassroots adverse drug reaction (ADR) monitoring organization in the country, to provide reference for the food and medicine monitoring organizations at different levels to develop ADR monitoring system, so as to better serve the overall safety monitoring of the medicine, medical device and cosmetic product. Methods Questionnaire survey was used to conduct research on the current status of the local adverse drug reaction monitoring system in our country. Results and Conclusion Through analyzing current status, common issues of the grassroots ADR monitoring organizations are discussed. These issues include incomplete reform progress, insufficient organization functions, most of the organizations not being independent, personnel team needing improvement, etc. The author makes proposals to the future local adverse drug reaction monitoring system development in the country and gives constructive advices to all levels of the monitoring departments to improve the monitoring system development.%目的:对当前全国基层药品不良反应监测机构现状进行分析,旨在为各级食品药品监督管理部门促进药品不良反应监测体系建设提供参考,更好地服务药品、医疗器械、化妆品上市后安全性监管工作大局。方法通过问卷调研的方式对我国目前基层药品不良反应监测体系建设现状进行了调研。结果与结论通过现状分析,讨论了基层药品不良反应监测技术机构存在的普遍问题,如改革进程尚未完成、机构职责还不健全、机构设置多未独立、人员队伍建设尚需加强等,并对未来全国基层药品不良反应监测体系建设提出了愿景,对各级监管部门完善监测体系建设工作提出了建设性的意见。

  6. Charge Tags for Most Comprehensive ESI-MS Monitoring of Morita-Baylis-Hillman (MBH)/aza-MBH Reactions: Solid Mechanistic View and the Dualistic Role of the Charge Tagged Acrylate.

    Galaverna, Renan; Camilo, Nilton S; Godoi, Marla N; Coelho, Fernando; Eberlin, Marcos N


    Neutral and charge tagged reagents were used to investigate the mechanism of the classical Morita-Baylis-Hillman (MBH) reaction as well as its aza-version using mass spectrometry with electrospray ionization (ESI-MS). The use of an acrylate (activated alkene) with a methylimidazolium ion as a charge tag eliminates the requirement for adding acids as ESI(+) additives, which are normally used to favor protonation and therefore detection of reaction partners (reagents, intermediates, and products) by ESI(+)-MS. For both charge tagged reactions (MBH/aza-MBH), most reactants, intermediates, and the final adducts were efficiently detected in the form of abundant doubly and singly charged ions. Characterization of the reactions partners was performed via both tandem mass spectrometry (ESI(+)-MS/MS) and accurate m/z measurements. The charge tagged reactions also showed faster conversion rates when compare to the neutral reaction, indicating a dualistic role for the charge tagged acrylate. It acts as both the reagent and a cocatalyst due to the inherent ionic-coordination nature of the methylimidazolium ion, which stabilizes the zwitterionic intermediates and reagents through different types of coordination ion pairs. Hemiacetal intermediates for the rate-limiting proton transfer step were also intercepted and characterized for both classical and aza-MBH charge tagged reactions.

  7. Advances and applications of selective reaction monitoring technology in proteomics study%选择性反应监测技术在蛋白质组学研究中的进展及应用

    单亦初; 张丽华; 张玉奎


    选择性反应监测(SRM)技术作为一种重要的定向蛋白质分析技术,通过选择性检测特定母离子和子离子来排除非目标组分的干扰,增强了检测灵敏度和定量准确度,具有选择性高、重复性好、灵敏度高、动态范围宽等优点,已被广泛应用于定量蛋白质组学研究,在生命科学领域发挥着至关重要的作用。本文从分析通量、检测灵敏度、定量方法以及相关软件资源4个方面,对近期 SRM 技术的研究进展进行了综述。然后,对 SRM 技术在蛋白质组学研究包括生物标志物验证、蛋白质翻译后修饰研究、生物工程以及信号通路分析等领域中的应用进行了概述。最后,本文对 SRM 技术的应用以及发展前景进行了展望。%As an important technology for targeted protein analysis,selective reaction monito-ring technology(SRM)improves the detection sensitivity and quantification accuracy by elimi-nating the interference of impurities and co-eluting peptides by selective detection of specific mother ions and daughter ions. It has been widely applied to the quantitative proteomics study due to the advantages of high selectivity,excellent reproducibility,high sensitivity and wide dynamic range and plays an important role in the area of life science. For the quantitative analy-sis of the complex samples with wide dynamic range,the throughput of analysis and detection sensitivity still need to be improved. Moreover,various quantification strategies have been pro-posed to improve the accuracy and precision of quantification. Furthermore,data processing becomes more and more important with the application of SRM technology to the analysis of complex samples. In this work,the recent development of SRM technology is reviewed from the above mentioned aspects. Since SRM technology gains wider applications along with the technological development,its applications in the area of proteomics quantitative study

  8. Spallation reactions; Reactions de spallation

    Cugon, J.


    Spallation reactions dominate the interactions of hadrons with nuclei in the GeV range (from {approx} 0.1 to {approx} 10 GeV). They correspond to a sometimes important ejection of light particles leaving most of the time a residue of mass commensurate with the target mass. The main features of the experimental data are briefly reviewed. The most successful theoretical model, namely the intranuclear cascade + evaporation model, is presented. Its physical content, results and possible improvements are critically discussed. Alternative approaches are shortly reviewed. (author). 84 refs.

  9. Monitoring madness

    Blankinship, S.


    High quality continuous emission monitoring capability can be as essential as high quality emission control equipment. Future mercury monitoring and control requirements add to the justification for better CEMS. The article discusses two prominent mercury measurement methods - the cold vapour atomic absorptive spectrometer (CVAAs) and the atomic absorptive spectrometer (AFS). It stresses the importance of maintaining a CEMS. 1 photo.

  10. Mobility Monitor

    Schæbel, Anne-Lise; Dybbro, Karina Løvendahl; Andersen, Lisbeth Støvring;


    Undersøgelse af digital monitorering af plejehjemsbeboeres vendinger under søvn på Fremtidens Plejehjem, Nørresundby......Undersøgelse af digital monitorering af plejehjemsbeboeres vendinger under søvn på Fremtidens Plejehjem, Nørresundby...

  11. Stochastic discrete event simulation of germinal center reactions

    Figge, MT


    We introduce a generic reaction-diffusion model for germinal center reactions and perform numerical simulations within a stochastic discrete event approach. In contrast to the frequently used deterministic continuum approach, each single reaction event is monitored in space and time in order to simu

  12. 药品不良反应信号的验证和统计分析研究方法的探索——基于克林霉素注射剂致肾毒性的不良反应监测数据%Exploration on Adverse Drug Reaction Signal Detection, Validation and Statistics Analysis Methods: Based on the Clindamycin Injection's Renal Toxicity Adverse Reaction Monitoring Data.

    路长飞; 田春华; 田月洁; 刘翠丽; 谢彦军


    目的 探索自愿报告药品不良反应信号的提取、验证及分析研究方法和模式.方法 利用比例失衡法和单因素分析方法,对国家药品不良反应数据库中有关克林霉素注射剂肾毒性的不良反应数据,进行信号的提取、验证和分析.结果 克林霉素注射剂致肾损害的ROR值为65.0,盐酸盐和磷酸酯致肾损害的ROR值分别为114.0、14.7;调整年龄、单次给药剂量后,盐酸克林霉素注射剂致肾损害的风险分别是克林霉素磷酸酯注射剂的6.6倍和5.5倍(P <0.001);药品不良反应评价流程包括药品不良反应信号的提取、药品不良反应信号的验证、药品不良反应信号的分析研究3个流程.结论 克林霉素注射剂与肾毒性不良反应存在关联性,盐酸克林霉素注射剂致肾损害风险高于克林霉素磷酸酯注射剂,但其机制仍需要进一步研究分析;综合运用数据挖掘和统计方法,可在药品不良反应信号提取、验证和分析研究中提供更有利的证据.%Objective To establish the model of adverse drug reaction signal detection, validation and statistics analysis methods. Methods Using the measures of disproportionality and stratified analysis to establish the model of adverse drug reaction signal detection, validation and analysis research by the clindamycin injection's renal toxicity adverse reaction monitoring data. Rssults The ROR of clindamycin injection, clindamycin hydrochloride injection and clindamycin phosphate injection were 65.0, 114.0 and 14.7, respectively. The risks of renal damage of clindamycin hydrochloride injection were 6.6 times and 5.5 times than clindamycin phosphate injection after adjusting the age and single drug dose(P <0.001). It has been successfully established the model of adverse drug reaction signal detection, validation and analysis research. Conclusion There is strong relevance between clindamycin and renal toxicity adverse reaction, and the risk of renal

  13. Controlling chemical reactions of a single particle

    Ratschbacher, Lothar; Sias, Carlo; Köhl, Michael


    The control of chemical reactions is a recurring theme in physics and chemistry. Traditionally, chemical reactions have been investigated by tuning thermodynamic parameters, such as temperature or pressure. More recently, physical methods such as laser or magnetic field control have emerged to provide completely new experimental possibilities, in particular in the realm of cold collisions. The control of reaction pathways is also a critical component to implement molecular quantum information processing. For these undertakings, single particles provide a clean and well-controlled experimental system. Here, we report on the experimental tuning of the exchange reaction rates of a single trapped ion with ultracold neutral atoms by exerting control over both their quantum states. We observe the influence of the hyperfine interaction on chemical reaction rates and branching ratios, and monitor the kinematics of the reaction products. These investigations advance chemistry with single trapped particles towards achi...

  14. Combustion kinetics and reaction pathways

    Klemm, R.B.; Sutherland, J.W. [Brookhaven National Laboratory, Upton, NY (United States)


    This project is focused on the fundamental chemistry of combustion. The overall objectives are to determine rate constants for elementary reactions and to elucidate the pathways of multichannel reactions. A multitechnique approach that features three independent experiments provides unique capabilities in performing reliable kinetic measurements over an exceptionally wide range in temperature, 300 to 2500 K. Recent kinetic work has focused on experimental studies and theoretical calculations of the methane dissociation system (CH{sub 4} + Ar {yields} CH{sub 3} + H + Ar and H + CH{sub 4} {yields} CH{sub 3} + H{sub 2}). Additionally, a discharge flow-photoionization mass spectrometer (DF-PIMS) experiment is used to determine branching fractions for multichannel reactions and to measure ionization thresholds of free radicals. Thus, these photoionization experiments generate data that are relevant to both reaction pathways studies (reaction dynamics) and fundamental thermochemical research. Two distinct advantages of performing PIMS with high intensity, tunable vacuum ultraviolet light at the National Synchrotron Light Source are high detection sensitivity and exceptional selectivity in monitoring radical species.

  15. Monarch Monitoring

    US Fish and Wildlife Service, Department of the Interior — The US Fish and Wildlife Service has engaged in a multi-partnered, integrated strategy for monitoring conservation of the monarch butterfly (Danaus plexippus...

  16. Monitoring Hadoop

    Singh, Gurmukh


    This book is useful for Hadoop administrators who need to learn how to monitor and diagnose their clusters. Also, the book will prove useful for new users of the technology, as the language used is simple and easy to grasp.

  17. Recombination monitor

    Zhang, S. Y. [Brookhaven National Lab. (BNL), Upton, NY (United States); Blaskiewicz, M. [Brookhaven National Lab. (BNL), Upton, NY (United States)


    This is a brief report on LEReC recombination monitor design considerations. The recombination produced Au78+ ion rate is reviewed. Based on this two designs are discussed. One is to use the large dispersion lattice. It is shown that even with the large separation of the Au78+ beam from the Au79+ beam, the continued monitoring of the recombination is not possible. Accumulation of Au78+ ions is needed, plus collimation of the Au79+ beam. In another design, it is shown that the recombination monitor can be built based on the proposed scheme with the nominal lattice. From machine operation point of view, this design is preferable. Finally, possible studies and the alternative strategies with the basic goal of the monitor are discussed.

  18. Bayesian Monitoring.

    Kirstein, Roland


    This paper presents a modification of the inspection game: The ?Bayesian Monitoring? model rests on the assumption that judges are interested in enforcing compliant behavior and making correct decisions. They may base their judgements on an informative but imperfect signal which can be generated costlessly. In the original inspection game, monitoring is costly and generates a perfectly informative signal. While the inspection game has only one mixed strategy equilibrium, three Perfect Bayesia...

  19. Catalysis of Photochemical Reactions.

    Albini, A.


    Offers a classification system of catalytic effects in photochemical reactions, contrasting characteristic properties of photochemical and thermal reactions. Discusses catalysis and sensitization, examples of catalyzed reactions of excepted states, complexing ground state substrates, and catalysis of primary photoproducts. (JM)

  20. Calibration of the radiation monitors from DESY and SPring-8 at the quasi-mono-energetic neutron beams using 100 and 300 MeV 7Li(p,n) reaction at RCNP in Osaka Japan in November 2014

    Leuschner, Albrecht; Asano, Yoshihiro; Klett, Alfred


    At the ring cyclotron facility of the Research Center for Nuclear Physics (RCNP) Osaka University, Osaka, Japan a series of measurement campaigns had been continued with quasi mono-energetic neutron beams in November 2014. A 7Li target was bombarded with 100 and 300 MeV protons and the generated neutron beams were directed into a long time-of-flight tunnel at 0 and 25 degrees deflection angle with respect to the proton beam. At a distance of 41 m the cross section of the neutron beam was large enough for the illumination of square meter sized objects like extended range rem-counters. The research institutes SPring-8/RIKEN, Japan, and DESY, Germany, participated in this campaign for the calibration of 4 different types of active ambient dose rate monitors: LB 6411, LB 6411-Pb, LB 6419 and LB 6420. The measurements of their responses are reported and compared with the calculated values.

  1. [Allergic reactions to transfusion].

    Hergon, E; Paitre, M L; Coeffic, B; Piard, N; Bidet, J M


    Frequent allergic reactions following transfusion are observed. Usually, they are benign but sometimes we observe severe allergic reactions. Adverse reactions may be brought about by least two mechanisms. First, immediate-type hypersensibility reactions due to IgE. Secondly, anaphylactic-type reactions due to interaction between transfused IgA and class specific anti IgA in the recipient's plasma. They are characterized by their severest form (anaphylactic shock). The frequency of severe reactions following the transfusion blood plasma is very low. These transfusion reactions are complement-mediated and kinins-mediated. Prevention of allergic reactions is necessary among blood donors and recipients.

  2. Liquid chromatographic-mass spectrometric method for ...

    spectrometric (LC-MS/MS) method for the quantitative determination of two dermatological drugs, ... analyte quantitation monitored by multiple reaction monitoring (MRM) mode. ... a correlation coefficient (r2) ≥ 0.999 and 0.998 for finasteride and ... of the split tablets fell outside of the proxy USP specification for at least.

  3. Air Quality Monitoring Programme

    Kemp, K.; Palmgren, F.

    The air quality in Danish cities has been monitored continuously since 1982 within the Danish Air Quality (LMP) network. The aim has been to follow the concentration levels of toxic pollutants in the urban atmosphere and to provide the necessary knowledge to assess the trends, to perform source...... apportionment, and to evaluate the chemical reactions and the dispersion of the pollutants in the atmosphere. In 2002 the air quality was measured in four Danish cities and at two background sites. NO2 and PM10 were at several stations found in concentrations above the new EU limit values, which the Member...

  4. Air Quality Monitoring Programme

    Kemp, K.; Palmgren, F.

    The air quality in Danish cities has been monitored continuously since 1982 within the Danish Air Quality (LMP) network. The aim has been to follow the concentration levels of toxic pollutants in the urban atmosphere and to provide the necessary knowledge to assess the trends, to perform source...... apportionment, and to evaluate the chemical reactions and the dispersion of the pollutants in the atmosphere. In 2002 the air quality was measured in four Danish cities and at two background sites. NO2 and PM10 were at several stations found in concentrations above the new EU limit values, which the Member...

  5. Action Monitoring and Perfectionism in Anorexia Nervosa

    Pieters, Guido L. M.; de Bruijn, Ellen R. A.; Maas, Yvonne; Hulstijn, Wouter; Vandereycken, Walter; Peuskens, Joseph; Sabbe, Bernard G.


    To study action monitoring in anorexia nervosa, behavioral and EEG measures were obtained in underweight anorexia nervosa patients (n=17) and matched healthy controls (n=19) while performing a speeded choice-reaction task. Our main measures of interest were questionnaire outcomes, reaction times, error rates, and the error-related negativity ERP…

  6. Action monitoring and perfectionism in anorexia nervosa

    Pieters, G.L.M.; Bruijn, E.R.A. de; Maas, Y.J.; Hulstijn, W.; Eycken, W. van der; Peuskens, J.; Sabbe, B.G.C.C.


    To study action monitoring in anorexia nervosa, behavioral and EEG measures were obtained in underweight anorexia nervosa patients (n = 17) and matched healthy controls (n = 19) while performing a speeded choice-reaction task. Our main measures of interest were questionnaire outcomes, reaction times

  7. Action monitoring and perfectionism in anorexia nervosa

    Pieters, G.L.M.; Bruijn, E.R.A. de; Maas, Y.J.; Hulstijn, W.; Eycken, W. van der; Peuskens, J.; Sabbe, B.G.C.C.


    To study action monitoring in anorexia nervosa, behavioral and EEG measures were obtained in underweight anorexia nervosa patients (n = 17) and matched healthy controls (n = 19) while performing a speeded choice-reaction task. Our main measures of interest were questionnaire outcomes, reaction times

  8. Action Monitoring and Perfectionism in Anorexia Nervosa

    Pieters, Guido L. M.; de Bruijn, Ellen R. A.; Maas, Yvonne; Hulstijn, Wouter; Vandereycken, Walter; Peuskens, Joseph; Sabbe, Bernard G.


    To study action monitoring in anorexia nervosa, behavioral and EEG measures were obtained in underweight anorexia nervosa patients (n=17) and matched healthy controls (n=19) while performing a speeded choice-reaction task. Our main measures of interest were questionnaire outcomes, reaction times, error rates, and the error-related negativity ERP…

  9. Autocatalysis-driven clock reaction II: kinetics of the pentathionate-periodate reaction.

    Xu, Li; Horváth, Attila K


    The pentathionate-periodate reaction has been investigated by spectrophotometrically monitoring the total amount of iodine evolved in the presence of phosphoric acid/dihydrogen phosphate buffer at 468 nm. The majority of the main characteristics of the title system is very reminiscent of that found recently in the pentathionate-iodate reaction, a system that led us to classify generally the clock reactions. Along with the pentathionate-iodate reaction the title system is proposed to belong to the autocatalysis-driven clock reactions as well. The kinetic model of the pentathionate-iodate system published recently was implemented by the necessary reactions of periodate to compose a 24-step kinetic model in which the mechanisms of the pentathionate-iodine, pentathionate-iodate, bisulfite-periodate, bisulfite-iodate, iodide-periodate, and the well-known Dushman reactions are combined. A thorough analysis revealed that the direct pentathionate-periodate reaction plays a role only to produce iodide ion via a finite sequence of reactions, and once its concentration reaches a certain level, the reaction is almost exclusively governed by the pentathionate-iodine, the iodide-periodate, and the Dushman reactions. As expected strong catalytic effect of the buffer composition is also found that can readily be explained by its well-known catalytic influence on the Dushman reaction.

  10. Condition Monitoring of Corrosive Sulfur Reaction in Transformer by Copper Ion Analysis%利用铜离子质量分数监测变压器中硫腐蚀状态的研究

    万涛; 钱晖; 冯兵; 周舟; 龚尚昆


    In order to investigate monitoring methods of sulfur corrosion in transformer,the copper content in oil and the sulfur-corrosion test results of 40 operating transformers were compared.Moreover,dynamic copper strip corrosion was tested by simulation in transformer oil samples filled with nitrogen,air and oxygen,respectively,and the change of copper content in oil and copper sulfide on copper strip and the influence of oxygen in the corrosion process were determined.The results showed that the consistency between the copper content tests and the corrosive sulfur tests exceeded 70%.The amounts of copper ion in oil and cuprous sulfide on copper strip both increased while the corrosion developed,indicating that copper corrosion of a transformer could be effectively monitored through copper content analysis.Meanwhile,corrosive sulfur tests could accurately reflect the accumulation of cuprous sulfide on copper strip from the color of copper strip.In the absence of oxygen,the main copper corrosion process should be copper→copper complex ion→cuprous sulfide,and the oxygen-contained copper corrosion process includes both copper→ copper oxide→copper complex ion→cuprous sulfide and copper→copper complex ion→cuprous sulfide.%为了研究变压器中硫腐蚀作用的监测方法,考察了40台运行变压器油中铜离子质量分数与腐蚀性硫测试结果的关系.将变压器油样品充入氮气、空气和氧气条件下进行了腐蚀过程动态模拟试验,确定了铜腐蚀过程中油中铜离子和铜片表面元素含量变化的规律和氧气含量的影响.结果表明,铜离子质量分数检测与腐蚀性硫试验一致性>70%,油中铜离子和铜片表面硫化亚铜离子质量分数随腐蚀过程不断增加,通过铜离子质量分数检测能够有效监测变压器铜腐蚀状态;腐蚀性硫试验中铜片颜色能够准确反映硫化亚铜离子质量分数变化.不含氧气时,铜的腐蚀过程主

  11. Discussion on the Inspiration for the Practice of Adverse Drug Reaction Monitoring in China by FDA "Sentinel Initiative"%试论FDA"哨点行动"对我国药品不良反应监测工作的启示



    By introducing the executive summary of sentinel initiative, the sentinel system vision, progress building the sentinel system, progress ensuring security and privacy, to analyse the practical meaning and inspiration for Adverse Drug Reaction(ADR) monitoring in China by the sentinel system and try to establish the fundamental principle and developmental trend of ADR monitoring in the current period.%通过全面介绍美国FDA 的哨点行动概况、哨点系统的特点和作用、哨点系统的建设进程、数据安全及隐私保护等方面内容,分析了哨点系统这种主动监测模式对于我国开展药品不良反应监测工作的现实意义和启发,并尝试提出现阶段我国药品不良反应监测工作发展的基本原则和方向.

  12. Targeting MUC1 mediated tumor stromal metabolic interaction in Triple negative Breast Cancer


    plate reader (Biotek, USA). Quantitative Real-Time Polymerase Chain Reaction Quantitative real-time polymerase chain reaction (qPCR) was 384 Well Optical Reaction Plates (Applied Biosystems) using SYBRGreen PCR Master Mix (Roche). Reactions were carried out on an ABI 7500...suspended in equal volumes of LC-MS grade water and 10 µl were utilized for LC-MS/MS using multiple reaction monitoring (MRM) method described

  13. Energy Monitoring

    Hansen, Claus T.; Madsen, Dines; Christiensen, Thomas

    Energy measurement has become an important aspect of our daily lives since we have learned that energy consumption, is one of the main source of global warming. Measuring instruments varies from a simple watt-meter to more sophisticated microprocessor control devices. The negative effects...... that fossil fuels induce on our environment has forced us to research renewable energy such as sunlight, wind etc. This new environmental awareness has also helped us to realize the importance of monitoring and controlling our energy use. The main purpose in this research is to introduce a more sophisticated...... but affordable way to monitor energy consumption of individuals or groups of home appliances. By knowing their consumption the utilization can be regulated for more efficient use. A prototype system has been constructed to demonstrate our idea....

  14. Energy Monitoring

    Hansen, Claus T.; Madsen, Dines; Christiensen, Thomas

    Energy measurement has become an important aspect of our daily lives since we have learned that energy consumption, is one of the main source of global warming. Measuring instruments varies from a simple watt-meter to more sophisticated microprocessor control devices. The negative effects...... that fossil fuels induce on our environment has forced us to research renewable energy such as sunlight, wind etc. This new environmental awareness has also helped us to realize the importance of monitoring and controlling our energy use. The main purpose in this research is to introduce a more sophisticated...... but affordable way to monitor energy consumption of individuals or groups of home appliances. By knowing their consumption the utilization can be regulated for more efficient use. A prototype system has been constructed to demonstrate our idea....

  15. Material monitoring

    Kotter, W.; Zirker, L.; Hancock, J.A.


    Waste Reduction Operations Complex (WROC) facilities are located at the Idaho National Engineering Laboratory (INEL). The overall goal for the Pollution Prevention/Waste Minimization Unit is to identify and establish the correct amount of waste generated so that it can be reduced. Quarterly, the INEL Pollution Prevention (P2) Unit compares the projected amount of waste generated per process with the actual amount generated. Examples of waste streams that would be addresses for our facility would include be are not limited to: Maintenance, Upgrades, Office and Scrap Metal. There are three potential sources of this variance: inaccurate identification of those who generate the waste; inaccurate identification of the process that generates the waste; and inaccurate measurement of the actual amount generated. The Materials Monitoring Program was proposed to identify the sources of variance and reduce the variance to an acceptable level. Prior to the implementation of the Material Monitoring Program, all information that was gathered and recorded was done so through an informal estimation of waste generated by various personnel concerned with each processes. Due to the inaccuracy of the prior information gathering system, the Material Monitoring Program was established. The heart of this program consists of two main parts. In the first part potential waste generators provide information on projected waste generation process. In the second part, Maintenance, Office, Scrap Metal and Facility Upgrade wastes from given processes is disposed within the appropriate bin dedicated to that process. The Material Monitoring Program allows for the more accurate gathering of information on the various waste types that are being generated quarterly.

  16. Double Pion Production Reactions

    Oset, E; Cano, F; Hernández, E; Kamalov, S S; Nacher, J C; Tejedor, J A G


    We report on reactions producing two pions induced by real and virtual photons or nucleons. The role of different resonances in these reactions is emphasized. Novel results on coherent two pion photoproduction in nuclei are also reported.

  17. Microfluidic chemical reaction circuits

    Lee, Chung-cheng; Sui, Guodong; Elizarov, Arkadij; Kolb, Hartmuth C.; Huang, Jiang; Heath, James R.; Phelps, Michael E.; Quake, Stephen R.; Tseng, Hsian-rong; Wyatt, Paul; Daridon, Antoine


    New microfluidic devices, useful for carrying out chemical reactions, are provided. The devices are adapted for on-chip solvent exchange, chemical processes requiring multiple chemical reactions, and rapid concentration of reagents.

  18. Microscale Thermite Reactions.

    Arnaiz, Francisco J.; Aguado, Rafael; Arnaiz, Susana


    Describes the adaptation of thermite (aluminum with metal oxides) reactions from whole-class demonstrations to student-run micro-reactions. Lists detailed directions and possible variations of the experiment. (WRM)

  19. Chemical transport reactions

    Schäfer, Harald


    Chemical Transport Reactions focuses on the processes and reactions involved in the transport of solid or liquid substances to form vapor phase reaction products. The publication first offers information on experimental and theoretical principles and the transport of solid substances and its special applications. Discussions focus on calculation of the transport effect of heterogeneous equilibria for a gas motion between equilibrium spaces; transport effect and the thermodynamic quantities of the transport reaction; separation and purification of substances by means of material transport; and

  20. Reaction systems with precipitation

    Marek Rogalski


    Full Text Available This article proposes expanding Reaction Systems of Ehrenfeucht and Rozenberg by incorporating precipitation reactions into it. This improves the computing power of Reaction Systems by allowing us to implement a stack. This addition enables us to implement a Deterministic Pushdown Automaton.

  1. Technology monitoring; Technologie-Monitoring

    Eicher, H.; Rigassi, R. [Eicher und Pauli AG, Liestal (Switzerland); Ott, W. [Econcept AG, Zuerich (Switzerland)


    This study made for the Swiss Federal Office of Energy (SFOE) examines ways of systematically monitoring energy technology development and the cost of such technologies in order to pave the way to a basis for judging the economic development of new energy technologies. Initial results of a survey of the past development of these technologies are presented and estimates are made of future developments in the areas of motor-based combined heat and power systems, fuel-cell heating units for single-family homes and apartment buildings, air/water heat pumps for new housing projects and high-performance thermal insulation. The methodology used for the monitoring and analysis of the various technologies is described. Tables and diagrams illustrate the present situation and development potential of various fields of technology.

  2. Monitoring microcirculation.

    Ocak, Işık; Kara, Atila; Ince, Can


    The clinical relevance of microcirculation and its bedside observation started gaining importance in the 1990s since the introduction of hand-held video microscopes. From then, this technology has been continuously developed, and its clinical relevance has been established in more than 400 studies. In this paper, we review the different types of video microscopes, their application techniques, the microcirculation of different organ systems, the analysis methods, and the software and scoring systems. The main focus of this review will be on the state-of-art technique, CytoCam-incident dark-field imaging, and the most recent technological and technical updates concerning microcirculation monitoring.

  3. Cardiac event monitors

    ... ECG) - ambulatory; Continuous electrocardiograms (EKGs); Holter monitors; Transtelephonic event monitors ... attached. You can carry or wear a cardiac event monitor up to 30 days. You carry the ...

  4. Enzyme Reactions in Nanoporous, Picoliter Volume Containers

    Siuti, Piro [ORNL; Retterer, Scott T [ORNL; Choi, Chang Kyoung [Michigan Technological University; Doktycz, Mitchel John [ORNL


    Advancements in nanoscale fabrication allow creation of small volume reaction containers that can facilitate the screening and characterization of enzymes. A porous, ~19 pL volume vessel has been used in this work to carry out enzyme reactions under varying substrate concentrations. Glucose oxidase and horseradish peroxidase can be contained in these structures and diffusively fed with a solution containing glucose and the fluorogenic substrate Amplex Red through the engineered nanoscale pore structure. Fluorescent microscopy was used to monitor the reaction, which was carried out under microfluidic control. Kinetic characteristics of the enzyme were evaluated and compared with results from conventional scale reactions. These picoliter, nanoporous containers can facilitate quick determination of enzyme kinetics in microfluidic systems without the requirement of surface tethering and can be used for applications in drug discovery, clinical diagnostics and high-throughput screening.

  5. Adverse drug reactions in hospitalized Colombian children.

    de Las Salas, Roxana; Díaz-Agudelo, Daniela; Burgos-Flórez, Francisco Javier; Vaca, Claudia; Serrano-Meriño, Dolores Vanessa


    The occurrence of adverse drug reactions is an important issue due to the lack of drug safety data in children. To describe the Adverse Drug Reactions in inpatient children under 6 years of age in two general pediatrics wards located in Barranquilla, Colombia. A prospective cohort study based on intensive pharmacovigilance was conducted during six months in order to monitor the emergence of Adverse Drug Reactions in inpatients children under 6 years of age with at least one medication prescribed. The study was conducted in two pediatric wards of two hospitals located in Barranquilla, Colombia. Naranjo´s Algorithm was used to evaluate imputability, the modified Hartwig and Siegel assessment scale to establish severity and the Schumock and Thornton criteria to determine preventability. Of a total of 772 monitored patients, 156 Adverse Drug Reactions were detected on 147 children. The cumulative incidence of Adverse Drug Reactions was 19.0% (147/772); the incidence density was 37.6 Adverse Drug Reactions per 1,000 patients-days (147/3,913). The frequency was higher in children under 2 years of age (12.7%). Emergence of Adverse Drug Reactions was higher in male patients (RR= 1.66; 95% CI= 1.22-2.22, p= 0.001) and in those who used systemic antibiotics (RR= 1.82; 95% CI= 1.17-2.82, p= 0.005). Adverse Drug Reactions are common among hospitalized children and represent an additional burden of morbidity and risk, particularly in those who used several medicines, including antibiotics.

  6. Monitoring Leverage

    Geanakoplos, John; Heje Pedersen, Lasse


    We argue that leverage is a central element of economic cycles and discuss how leverage can be properly monitored. While traditionally the interest rate has been regarded as the single key feature of a loan, we contend that the size of the loan, i.e., the leverage, is in fact a more important...... measure of systemic risk. Indeed, systemic crises tend to erupt when highly leveraged economic agents are forced to deleverage, sending the economy into recession. We emphasize the importance of measuring both the average leverage on old loans (which captures the economy's vulnerability) and the leverage...... offered on new loans (which captures current credit conditions) since the economy enters a crisis when leverage on new loans is low and leverage on old loans is high. While leverage plays an important role in several economic models, the data on leverage is model-free and simply needs to be collected...

  7. Treaty Monitoring

    Canty, M.; Lingenfelder, I.; Nielsen, Allan Aasbjerg;


    This volume provides the reader with an overview of the state-of-the-art Earth Observation (EO) related research that deals with national and international security. An interdisciplinary approach was adopted in this book in order to provide the reader with a broad understanding on the uses...... of remote sensing technologies. The book therefore comprises management aspects (issues and priorities of security research, crisis response), applied methodologies and process chains (treaty monitoring, estimation of population densities and characteristics, border permeability models, damage assessment......, as well as project managers and decision makers working in the field of security having an interest in technical solutions. The integrative use of many figures and sample images are ideal in enabling the non-technical reader to grasp quickly the modern technologies that are being researched in the area...

  8. Intracranial pressure monitoring

    ICP monitoring; CSF pressure monitoring ... There are 3 ways to monitor pressure in the skull (intracranial pressure). INTRAVENTRICULAR CATHETER The intraventricular catheter is the most accurate monitoring method. To insert an intraventricular catheter, a ...

  9. Cross section measurements of {sup 75}As(α,xn){sup 76,77,78}Br and {sup 75}As(α,x){sup 74}As nuclear reactions using the monitor radionuclides {sup 67}Ga and {sup 66}Ga for beam evaluation

    Breunig, Katharina; Spahn, Ingo; Spellerberg, Stefan; Scholten, Bernhard; Coenen, Heinz H. [Forschungszentrum Juelich (Germany). Inst. for Neuroscience and Medicine, INM-5: Nuclear Chemistry; Hermanne, Alex [Vrije Univ. Brussel (VUB) (Belgium). Cyclotron Lab.


    For the production of the medically interesting radionuclides {sup 76}Br and {sup 77}Br cross sections of α-particle induced reactions on arsenic, leading to the formation of {sup 76,77,78}Br as well as to the non-isotopic impurity {sup 74}As, were measured from their thresholds up to 37 MeV. Sediments of elemental arsenic were used as targets and irradiated, using the established stacked-foil technique. In order to remove discrepancies of the existing literature data, the cross section ratios of the monitor nuclides {sup 67}Ga/{sup 66}Ga were used for determination of the α-particle energies as well as the effective beam current through all the stacks, thus inferring the experimental cross sections. Compared with the available excitation functions the new data indicate slightly divergent curve shapes. In the case of {sup 76}Br the excitation function seems to be shifted to somewhat lower α-particle energies, and also the maximum cross section of the formation of {sup 77}Br tends to be slightly lower compared with the curve recommended to date. In the case of a re-evaluation, these new data should be taken into account, as they may contribute to enhance the accuracy of the excitation functions.

  10. Noncanonical Reactions of Flavoenzymes

    Pablo Sobrado


    Full Text Available Enzymes containing flavin cofactors are predominantly involved in redox reactions in numerous cellular processes where the protein environment modulates the chemical reactivity of the flavin to either transfer one or two electrons. Some flavoenzymes catalyze reactions with no net redox change. In these reactions, the protein environment modulates the reactivity of the flavin to perform novel chemistries. Recent mechanistic and structural data supporting novel flavin functionalities in reactions catalyzed by chorismate synthase, type II isopentenyl diphosphate isomerase, UDP-galactopyranose mutase, and alkyl-dihydroxyacetonephosphate synthase are presented in this review. In these enzymes, the flavin plays either a direct role in acid/base reactions or as a nucleophile or electrophile. In addition, the flavin cofactor is proposed to function as a “molecular scaffold” in the formation of UDP-galactofuranose and alkyl-dihydroxyacetonephosphate by forming a covalent adduct with reaction intermediates.

  11. Selected Reaction Monitoring (SRM) frente a Western Blot

    Heredia Ponce, Zahira Maria; Urbano Gámez, Jose Alberto


    We propose the SRM technology as a complementary method to the Western Blot for the detection and quantification of proteins in a sample. The technique Western Blot has its own limitations: i) only a protein-of-choice is detected, ignoring any non-relevant proteins, ii) the sensitivity of the technique depends on the specificity of the antibody and iii) Western Blot is expensive and time-consuming. The advantages of SRM with respect Western Blot are remarkable: i) you can detect up to h...

  12. Longitudinal Monitoring of Public Reactions to the U.S

    J.D. Absher; A.G. Graefe; R.C. Burns


    Natural resource managers need to better understand the impact of fees on outdoor recreationists. The debate about recreation fees involves both operational issues such as revenue use and social issues such as justice and fairness. The recreation fee program of the US Forest Service is over ten years old and it is now possible to gauge some of the longitudinal effects...

  13. Reaction kinetics of polybutylene terephthalate polycondensation reaction

    Darda, P. J.; Hogendoorn, J. A.; Versteeg, G. F.; Souren, F.


    The kinetics of the forward polycondensation reaction of polybutylene terephthalate (PBT) has been investigated using thermogravimetric analysis (TGA). PBT - prepolymer with an initial degree of polymerization of 5.5 was used as starting material. The PBT prepolymer was prepared from dimethyl tereph

  14. Transfusion reaction - hemolytic

    ... of allergic transfusion reactions that do not cause hemolysis. ... transfusion, the transfusion must be stopped right away. Blood samples from the recipient (person getting the transfusion) and ...

  15. Desosamine in multicomponent reactions

    Achatz, Sepp; Dömling, Alexander


    Desosamine occurring ubiquitously in natural products is introduced into isocyanide based multicomponent reaction chemistry. Corresponding products are of potential interest for the design of novel antibiotics. © 2006.

  16. Metal-mullite reactions

    Loehman, R.E. [Sandia National Labs., Albuquerque, NM (United States); Tomsia, A.P. [Pask Research and Engineering, Berkeley, CA (United States)


    Mullite was reacted with pure Al and with Ti or Zr dissolved in Ag-Cu eutectic alloys at 1100 C in Ar. Analysis of the Ti and Zr-containing specimens showed reaction zones with compositions of Ti{sub 50}Cu{sub 3O}O{sub 20} and ZrO{sub 2}, respectively. The Al-mullite specimen showed much more extensive penetration into the ceramic and a more diffuse reaction zone than the other two systems. Al{sub 2}O{sub 3} and Si were the main reaction products for Al-mullite reaction.

  17. Reactions at Solid Surfaces

    Ertl, Gerhard


    Expanding on the ideas first presented in Gerhard Ertl's acclaimed Baker Lectures at Cornell University, Reactions at Solid Surfaces comprises an authoritative, self-contained, book-length introduction to surface reactions for both professional chemists and students alike. Outlining our present understanding of the fundamental processes underlying reactions at solid surfaces, the book provides the reader with a complete view of how chemistry works at surfaces, and how to understand and probe the dynamics of surface reactions. Comparing traditional surface probes with more modern ones, and brin

  18. Desosamine in multicomponent reactions

    Achatz, Sepp; Dömling, Alexander


    Desosamine occurring ubiquitously in natural products is introduced into isocyanide based multicomponent reaction chemistry. Corresponding products are of potential interest for the design of novel antibiotics. © 2006.

  19. Automatic NMR-based identification of chemical reaction types in mixtures of co-occurring reactions.

    Latino, Diogo A R S; Aires-de-Sousa, João


    The combination of chemoinformatics approaches with NMR techniques and the increasing availability of data allow the resolution of problems far beyond the original application of NMR in structure elucidation/verification. The diversity of applications can range from process monitoring, metabolic profiling, authentication of products, to quality control. An application related to the automatic analysis of complex mixtures concerns mixtures of chemical reactions. We encoded mixtures of chemical reactions with the difference between the (1)H NMR spectra of the products and the reactants. All the signals arising from all the reactants of the co-occurring reactions were taken together (a simulated spectrum of the mixture of reactants) and the same was done for products. The difference spectrum is taken as the representation of the mixture of chemical reactions. A data set of 181 chemical reactions was used, each reaction manually assigned to one of 6 types. From this dataset, we simulated mixtures where two reactions of different types would occur simultaneously. Automatic learning methods were trained to classify the reactions occurring in a mixture from the (1)H NMR-based descriptor of the mixture. Unsupervised learning methods (self-organizing maps) produced a reasonable clustering of the mixtures by reaction type, and allowed the correct classification of 80% and 63% of the mixtures in two independent test sets of different similarity to the training set. With random forests (RF), the percentage of correct classifications was increased to 99% and 80% for the same test sets. The RF probability associated to the predictions yielded a robust indication of their reliability. This study demonstrates the possibility of applying machine learning methods to automatically identify types of co-occurring chemical reactions from NMR data. Using no explicit structural information about the reactions participants, reaction elucidation is performed without structure elucidation of

  20. Contamination monitoring

    Alamares, A.L. [Philippine Nuclear Research Inst., Diliman, Quezon City (Philippines)


    By virture of Republic Act 2067, as amended the Philippine Atomic Energy Commission (PAEC), now renamed Philippine Nuclear Research Institute (PNRI) is the government agency charged with the regulations and control of radioactive materials in the Philippines. The protection against the hazards of non-ionizing radiation is being monitored by the Radiological Health Service (RHS) of the Department of Health pursuant to the provision of Presidental Decree 480. The RHS issues licenses for possession, handling, and use of x-ray machines and equipment, both industrial and medical, and provide radiation protection training to x-ray technologists and technicians. As part of its regulatory function, the PNRI is charged with the responsibility of assuring that the radiation workers and the public are protected from the hazards associated with the possession, handling, production, manufacturing, and the use of radioactive materials and atomic energy facilities in the Philippines. The protection of radiation workers from the hazards of ionizing radiation has always been a primary concern of PNRI and by limiting the exposure of radiation workers, the risk to population is kept to within acceptable level. In this paper, the following items are described: radiation protection program, radiation protection services, radiation control, and problems encountered/recommendation. (G.K.)

  1. Fluorogenic organocatalytic reactions

    Raeisolsadati Oskouei, M.


    In this thesis, we introduce fluorescence spectroscopy as a new tool to gain insight into the interactions between the substrates and catalyst during organocatalytic reactions. The ultimate goal is to resolve the kinetics of the binding and reaction steps and obtain detailed understanding of the

  2. Chemical burn or reaction

    ... this page: // Chemical burn or reaction To use the sharing features on this page, please enable JavaScript. Chemicals that touch skin can lead to a reaction on the skin, throughout the body, or both. ...

  3. Reactions to Attitudinal Deviancy.

    Levine, John M.; Allen, Vernon L.

    This paper presents a critical review of empirical and theoretical treatments of group reaction to attitudinal deviancy. Inspired by Festinger's (1950) ideas on resolution of attitudinal discrepancies in groups, Schachter (1951) conducted an experiment that has greatly influenced subsequent research and theory concerning reaction to attitudinal…

  4. Allergic reactions to vaccines.

    Wood, Robert A


    Anaphylactic reactions to vaccines are rare but do occur, and have been reported for nearly every vaccine. And while the reaction rate per each dose of vaccine is low, this is a common clinical question due in large part to the enormous numbers of vaccines administered. Reactions are most often due to vaccine constituents rather than the microbial components of the vaccine, but in many instances, the specific ingredient triggering the reaction cannot be definitively identified. Evaluation of patients with suspected vaccine reactions should begin by determining whether the symptoms and timing of the reaction were consistent with a true allergic reaction, followed by an assessment to determine whether the patient needs further doses of the vaccine in question, or similar vaccines, in the future. Skin and serologic testing to vaccines and vaccine constituents can then be performed to further assess the potential cause of the reaction and to develop a plan for future immunizations. Specific guidelines for the administration of influenza vaccines to egg allergic patients have been revised to allow virtually all patients to receive this vaccine in a straightforward manner. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  5. Electroweak precision observables ({\\boldmath $m_{\\rm W}$}, {\\boldmath $m_{\\rm top}$}) from ATLAS and CMS

    Piedra Gomez, Jonatan


    We present the latest ATLAS and CMS measurements of the top quark mass, the W boson mass, the effective Electroweak (EW) mixing angle and the on-shell EW mixing angle. In addition, the uncertainties for current and future measurements of EW parameters at hadron colliders are investigated.

  6. Chemical reaction and separation method

    Jansen, J.C.; Kapteijn, F.; Strous, S.A.


    The invention is directed to process for performing a chemical reaction in a reaction mixture, which reaction produces water as by-product, wherein the reaction mixture is in contact with a hydroxy sodalite membrane, through which water produced during the reaction is removed from the reaction mixtu

  7. Identifying Understudied Nuclear Reactions by Text-mining the EXFOR Experimental Nuclear Reaction Library

    Hirdt, J. A.; Brown, D. A.


    The EXFOR library contains the largest collection of experimental nuclear reaction data available as well as the data's bibliographic information and experimental details. We text-mined the REACTION and MONITOR fields of the ENTRYs in the EXFOR library in order to identify understudied reactions and quantities. Using the results of the text-mining, we created an undirected graph from the EXFOR datasets with each graph node representing a single reaction and quantity and graph links representing the various types of connections between these reactions and quantities. This graph is an abstract representation of the connections in EXFOR, similar to graphs of social networks, authorship networks, etc. We use various graph theoretical tools to identify important yet understudied reactions and quantities in EXFOR. Although we identified a few cross sections relevant for shielding applications and isotope production, mostly we identified charged particle fluence monitor cross sections. As a side effect of this work, we learn that our abstract graph is typical of other real-world graphs.

  8. Adverse drug reactions in West Africa

    Cliff-Eribo, Kennedy O.


    Adverse drug reaction (ADR) reports of countries varies due to differences in the prevalence of diseases and hence the types of drugs used. ADRs are a major health and economic burden worldwide. National health authorities monitor the safety of medicines to protect consumers from the hazards of drugs. ADR databases are also maintained from where reports are regularly evaluated to detect signals of new ADRs and determine the increase of those already known. A review of paediatric and genera...

  9. Correlation between y-type ions observed in ion trap and triple quadrupole mass spectrometers.

    Sherwood, Carly A; Eastham, Ashley; Lee, Lik Wee; Risler, Jenni; Vitek, Olga; Martin, Daniel B


    Multiple reaction monitoring mass spectrometry (MRM-MS) is a technique for high-sensitivity targeted analysis. In proteomics, MRM-MS can be used to monitor and quantify a peptide based on the production of expected fragment peaks from the selected peptide precursor ion. The choice of which fragment ions to monitor in order to achieve maximum sensitivity in MRM-MS can potentially be guided by existing MS/MS spectra. However, because the majority of discovery experiments are performed on ion trap platforms, there is concern in the field regarding the generalizability of these spectra to MRM-MS on a triple quadrupole instrument. In light of this concern, many operators perform an optimization step to determine the most intense fragments for a target peptide on a triple quadrupole mass spectrometer. We have addressed this issue by targeting, on a triple quadrupole, the top six y-ion peaks from ion trap-derived consensus library spectra for 258 doubly charged peptides from three different sample sets and quantifying the observed elution curves. This analysis revealed a strong correlation between the y-ion peak rank order and relative intensity across platforms. This suggests that y-type ions obtained from ion trap-based library spectra are well-suited for generating MRM-MS assays for triple quadrupoles and that optimization is not required for each target peptide.

  10. The DEdicated MONitor of EXotransits (DEMONEX): Seven Transits of XO-4b

    Villanueva, S; Gaudi, B S


    The DEdicated MONitor of EXotransits (DEMONEX) was a 20 inch robotic and automated telescope to monitor bright stars hosting transiting exoplanets to discover new planets and improve constraints on the properties of known transiting planetary systems. We present results for the misaligned hot Jupiter XO-4b containing 7 new transits from the DEMONEX telescope, including 3 full and 4 partial transits. We combine these data with archival light curves and archival radial velocity measurements to derive the host star mass $M_{*}=1.293_{-0.029}^{+0.030} M_\\odot$ and radius $R_{*}=1.554_{-0.030}^{+0.042} R_\\odot$ as well as the planet mass $M_{P}=1.615_{-0.099}^{+0.10} M_{\\rm J}$ and radius $R_{P}=1.317_{-0.029}^{+0.040} R_{\\rm J}$ and a refined ephemeris of $P=4.1250687\\pm0.0000024$ days and $T_{0}=2454758.18978\\pm0.00024 \\rm {BJD_{TDB}}$. We include archival Rossiter-McLaughlin measurements of XO-4 to infer the stellar spin-planetary orbit alignment $\\lambda=-40.0_{-7.5}^{+8.8}$ degrees. We test the effects of inc...

  11. The Reaction Wheel Pendulum

    Block, Daniel J; Spong, Mark W


    This monograph describes the Reaction Wheel Pendulum, the newest inverted-pendulum-like device for control education and research. We discuss the history and background of the reaction wheel pendulum and other similar experimental devices. We develop mathematical models of the reaction wheel pendulum in depth, including linear and nonlinear models, and models of the sensors and actuators that are used for feedback control. We treat various aspects of the control problem, from linear control of themotor, to stabilization of the pendulum about an equilibrium configuration using linear control, t

  12. Electron transfer reactions

    Cannon, R D


    Electron Transfer Reactions deals with the mechanisms of electron transfer reactions between metal ions in solution, as well as the electron exchange between atoms or molecules in either the gaseous or solid state. The book is divided into three parts. Part 1 covers the electron transfer between atoms and molecules in the gas state. Part 2 tackles the reaction paths of oxidation states and binuclear intermediates, as well as the mechanisms of electron transfer. Part 3 discusses the theories and models of the electron transfer process; theories and experiments involving bridged electron transfe

  13. Firefighter Nozzle Reaction

    Chin, Selena K.; Sunderland, Peter B.; Jomaas, Grunde


    Nozzle reaction and hose tension are analyzed using conservation of fluid momentum and assuming steady, inviscid flow and a flexible hose in frictionless contact with the ground. An expression that is independent of the bend angle is derived for the hose tension. If this tension is exceeded owing...... to anchor forces, the hose becomes straight. The nozzle reaction is found to equal the jet momentum flow rate, and it does not change when an elbow connects the hose to the nozzle. A forward force must be exerted by a firefighter or another anchor that matches the forward force that the jet would exert...... on a perpendicular wall. Three reaction expressions are derived, allowing it to be determined in terms of hose diameter, jet diameter, flow rate, and static pressure upstream of the nozzle. The nozzle reaction predictions used by the fire service are 56% to 90% of those obtained here for typical firefighting hand...

  14. Oral Hypersensitivity Reactions

    ... food, food additives, drugs, oral hygiene products, and dental materials. Q: Are there any specific foods that are ... dental treatment trigger a hypersensitivity reaction? A: Some dental materials used by the dentist can cause a hypersensitivity ...

  15. Response reactions: equilibrium coupling.

    Hoffmann, Eufrozina A; Nagypal, Istvan


    It is pointed out and illustrated in the present paper that if a homogeneous multiple equilibrium system containing k components and q species is composed of the reactants actually taken and their reactions contain only k + 1 species, then we have a unique representation with (q - k) stoichiometrically independent reactions (SIRs). We define these as coupling reactions. All the other possible combinations with k + 1 species are the coupled reactions that are in equilibrium when the (q - k) SIRs are in equilibrium. The response of the equilibrium state for perturbation is determined by the coupling and coupled equilibria. Depending on the circumstances and the actual thermodynamic data, the effect of coupled equilibria may overtake the effect of the coupling ones, leading to phenomena that are in apparent contradiction with Le Chatelier's principle.

  16. Autocatalysis in reaction networks.

    Deshpande, Abhishek; Gopalkrishnan, Manoj


    The persistence conjecture is a long-standing open problem in chemical reaction network theory. It concerns the behavior of solutions to coupled ODE systems that arise from applying mass-action kinetics to a network of chemical reactions. The idea is that if all reactions are reversible in a weak sense, then no species can go extinct. A notion that has been found useful in thinking about persistence is that of "critical siphon." We explore the combinatorics of critical siphons, with a view toward the persistence conjecture. We introduce the notions of "drainable" and "self-replicable" (or autocatalytic) siphons. We show that: Every minimal critical siphon is either drainable or self-replicable; reaction networks without drainable siphons are persistent; and nonautocatalytic weakly reversible networks are persistent. Our results clarify that the difficulties in proving the persistence conjecture are essentially due to competition between drainable and self-replicable siphons.

  17. Translated chemical reaction networks.

    Johnston, Matthew D


    Many biochemical and industrial applications involve complicated networks of simultaneously occurring chemical reactions. Under the assumption of mass action kinetics, the dynamics of these chemical reaction networks are governed by systems of polynomial ordinary differential equations. The steady states of these mass action systems have been analyzed via a variety of techniques, including stoichiometric network analysis, deficiency theory, and algebraic techniques (e.g., Gröbner bases). In this paper, we present a novel method for characterizing the steady states of mass action systems. Our method explicitly links a network's capacity to permit a particular class of steady states, called toric steady states, to topological properties of a generalized network called a translated chemical reaction network. These networks share their reaction vectors with their source network but are permitted to have different complex stoichiometries and different network topologies. We apply the results to examples drawn from the biochemical literature.

  18. Ofloxacin induced hypersensitivity reaction

    Hari Babu Ramineni


    Full Text Available Ofloxacin is a commonly used antimicrobial agent to combat various infections. The adverse profile of quinolones includes gastrointestinal symptoms, which are the most frequent, neuropsychiatric symptoms, hematologic abnormalities are less common. We report a rare case of ofloxacin induced hypersensitivity reaction in a 57 year old female patient with complaints of rashes over the axilla, upper limb and back, abdomen, thorax associated with exfoliation of skin all over the axilla associated with severe itching. Based on history and clinical examination patient was diagnosed as ofloxacin induced hypersensitivity reaction and was successfully treated with antihistamines and corticosteroids. Pharmacovigilance should be a part of patient care in order to reduce occurrence of adverse drug reaction and also encourage practitioners in reporting so as to gather more and more data regarding adverse drug reactions. [Int J Res Med Sci 2015; 3(1.000: 349-351

  19. Chemisorption And Precipitation Reactions

    The transport and bioavailability of chemical components within soils is, in part, controlled by partitioning between solids and solution. General terms used to describe these partitioning reactions include chemisorption and precipitation. Chemisorption is inclusive of the suit...

  20. Adverse reactions to sulfites

    Yang, William H.; Purchase, Emerson C.R.


    Sulfites are widely used as preservatives in the food and pharmaceutical industries. In the United States more than 250 cases of sulfite-related adverse reactions, including anaphylactic shock, asthmatic attacks, urticaria and angioedema, nausea, abdominal pain and diarrhea, seizures and death, have been reported, including 6 deaths allegedly associated with restaurant food containing sulfites. In Canada 10 sulfite-related adverse reactions have been documented, and 1 death suspected to be sulfite-related has occurred. The exact mechanism of sulfite-induced reactions is unknown. Practising physicians should be aware of the clinical manifestations of sulfite-related adverse reactions as well as which foods and pharmaceuticals contain sulfites. Cases should be reported to health officials and proper advice given to the victims to prevent further exposure to sulfites. The food industry, including beer and wine manufacturers, and the pharmaceutical industry should consider using alternative preservatives. In the interim, they should list any sulfites in their products. PMID:4052897

  1. Allergic reactions in anaesthesia

    Krøigaard, M; Garvey, L H; Menné, T;


    BACKGROUND: The aim of this retrospective survey of possible allergic reactions during anaesthesia was to investigate whether the cause suspected by anaesthetists involved corresponded with the cause found on subsequent investigation in the Danish Anaesthesia Allergy Centre (DAAC). METHODS: Case...... notes and anaesthetic charts from 111 reactions in 107 patients investigated in the DAAC were scrutinized for either suspicions of or warnings against specific substances stated to be the cause of the supposed allergic reaction. RESULTS: In 67 cases, one or more substances were suspected. In 49...... match, the right substance being suspected, but investigations showed an additional allergen or several substances, including the right substance being suspected. CONCLUSIONS: An informed guess is not a reliable way of determining the cause of a supposed allergic reaction during anaesthesia and may put...

  2. Oxygen evolution reaction catalysis

    Haber, Joel A.; Jin, Jian; Xiang, Chengxiang; Gregoire, John M.; Jones, Ryan J.; Guevarra, Dan W.; Shinde, Aniketa A.


    An Oxygen Evolution Reaction (OER) catalyst includes a metal oxide that includes oxygen, cerium, and one or more second metals. In some instances, the cerium is 10 to 80 molar % of the metals in the metal oxide and/or the catalyst includes two or more second metals. The OER catalyst can be included in or on an electrode. The electrode can be arranged in an oxygen evolution system such that the Oxygen Evolution Reaction occurs at the electrode.

  3. Meson production in + reactions

    H Machner; M Betigeri; J Bojowald; A Budzanowski; A Chatterjee; J Ernst; L Freindl; D Frekers; W Garske; K Grewer; A Hamacher; J Ilieva; L Jarczyk; K Kilian; S Kliczewski; W Klimala; D Kolev; T Kutsarova; J Lieb; H Machner; A Magiera; H Nann; L Pentchev; H S Plendl; D Protić; B Razen; P Von Rossen; B J Roy; R Siudak; J Smyrski; R V Srikantiah; A Strzałkowski; R Tsenov; K Zwoll


    Total and differential cross sections for the reactions $p+d → 3He + 0 with = ; and + → 3H + + were measured with the GEM detector at COSY for beam momenta between threshold and the maximum of the corresponding baryon resonance. For both reactions a strong forward–backward asymmetry was found. The data were compared with model calculations. The aspect of isospin symmetry breaking is studied.

  4. Adverse reactions to sulfites

    Yang, William H; Purchase, Emerson C.R.


    Sulfites are widely used as preservatives in the food and pharmaceutical industries. In the United States more than 250 cases of sulfite-related adverse reactions, including anaphylactic shock, asthmatic attacks, urticaria and angioedema, nausea, abdominal pain and diarrhea, seizures and death, have been reported, including 6 deaths allegedly associated with restaurant food containing sulfites. In Canada 10 sulfite-related adverse reactions have been documented, and 1 death suspected to be su...

  5. Holter and Event Monitors

    ... Share this page from the NHLBI on Twitter. Holter and Event Monitors Also known as ambulatory EKG; continuous EKG; EKG event monitors. Holter and event monitors are small, portable electrocardiogram devices ...

  6. A clinical analysis of monitoring vancomycin plasma concentration and adverse reactions in 32 cases of elderly patients%32例老年患者万古霉素血药浓度监测与不良反应的临床分析

    付晶; 施阳; 荆晓明; 王一凡; 王雷


    impairment (7.69%) and none hearing damage in patients treated with combination of antibiotic therapy. Therefore no correlation was concluded between the occurrence of adverse reactions and the combination therapy ( r=0.15, P>0.05). Conclusions In elderly patients over the age of 70 years, there is a higher incidence of kidney damage in the application of vancomycin. Thus, the monitoring of vancomycin plasma concentration in elderly patients has instructive significance in its clinical use.

  7. Monitoring Knowledge Base (MKB)

    U.S. Environmental Protection Agency — The Monitoring Knowledge Base (MKB) is a compilation of emissions measurement and monitoring techniques associated with air pollution control devices, industrial...

  8. Conductometric Microbiosensors for Environmental Monitoring

    Sergei V. Dzyadevych


    Full Text Available This review presents the principles of conductometric measurements in ionic media and the equivalent electrical circuits of different designs for conductometric measurements. These types of measurements were first applied for monitoring biocatalytic reactions. The use of conductometric microtransducers is then presented and detailed in the case of pollutant detection for environmental monitoring. Conductometric biosensors have advantages over other types of transducers: they can be produced through inexpensive thinfilm standard technology, no reference electrode is needed and differential mode measurements allow cancellation of a lot of interferences. The specifications obtained for the detection of different pesticides, herbicides and heavy metal ions, based on enzyme inhibition, are presented as well as those obtained for the detection of formaldehyde, 4- chlorophenol, nitrate and proteins as markers of dissolved organic carbon based on enzymatic microbiosensors.

  9. Monitoring Control Applications at CERN

    Bernard, F; Milcent, H; Petrova, L B; Varela, F


    The Industrial Controls and Engineering (EN-ICE) group [1] of the Engineering Department at CERN has produced, and is responsible for the operation of around 60 applications, which control critical processes in the domains of cryogenics, quench protection systems, power interlocks for the Large Hadron Collider and other subsystems of the accelerator complex. These applications require 24/7 operation and a quick reaction to problems. For this reason the EN-ICE group is presently developing the Monitoring Operation of cOntrols Networks (MOON) tool to detect, anticipate and inform of possible anomalies in the integrity of the applications. The tool builds on top of Simatic WinCC Open Architecture (WinCC OA) [2] SCADA and makes usage of the Joint COntrols Project (JCOP) [3] and the UNified INdustrial COntrol System (UNICOS) [4] Frameworks developed at CERN. The tool provides centralized monitoring and software management of the different elements integrating the control systems like Windows and L...

  10. Isolating Reactions at the Picoliter Scale: Parallel Control of Reaction Kinetics at the Liquid-Liquid Interface.

    Phan-Quang, Gia Chuong; Lee, Hiang Kwee; Ling, Xing Yi


    Miniaturized liquid-liquid interfacial reactors offer enhanced surface area and rapid confinement of compounds of opposite solubility, yet they are unable to provide in situ reaction monitoring at a molecular level at the interface. A picoreactor operative at the liquid-liquid interface is described, comprising plasmonic colloidosomes containing Ag octahedra strategically assembled at the water-in-decane emulsion interface. The plasmonic colloidosomes isolate ultrasmall amounts of solutions (<200 pL), allowing parallel monitoring of multiple reactions simultaneously. Using the surface-enhanced Raman spectroscopy (SERS) technique, in situ monitoring of the interfacial protonation of dimethyl yellow (p-dimethylaminoazobenzene (DY)) is performed, revealing an apparent rate constant of 0.09 min(-1) for the first-order reaction. The presence of isomeric products with similar physical properties is resolved, which would otherwise be indiscernible by other analytical methods.

  11. A possible candidate to be classified as an autocatalysis-driven clock reaction: kinetics of the pentathionate-iodate reaction.

    Xu, Li; Horváth, Attila K


    The pentathionate-iodate reaction has been investigated by spectrophotometrically monitoring the formation of the total amount of iodine at 468 nm in the presence of phosphoric acid/dihydrogen phosphate buffer. We noticed that iodine forms only after a fairly long time lag, and the inverse of time necessary to produce a certain amount of iodine is linearly proportional to the initial concentration of iodate ion and the square of the hydrogen ion concentration, while depending complexly on the concentration of substrate pentathionate. This reaction can therefore be treated as a clock reaction but differs from the original Landolt reaction in the sense that substrate pentathionate and the clock species iodine coexist for a relatively long time--due to their relatively slow direct reaction--depending on the experimental circumstances. Furthermore, we also provided experimental evidence that iodide ion acts as an autocatalyst of the system. A 14-step kinetic model is proposed in which the mechanisms of the pentathionate-iodine, bisulfite-iodate, and the well-known Dushman reactions are combined. A thorough analysis revealed that the direct pentathionate-iodate reaction plays a role only to produce iodide ions via a finite sequence of reactions, and once its concentration reaches a certain level, the reaction is almost exclusively governed by the pentathionate-iodine and the Dushman reactions. As expected, a strong catalytic effect of the buffer composition is also found that can readily be explained by its well-known catalytic influence on the original Dushman reaction.

  12. Immediate reaction to clarithromycin.

    Gangemi, S; Ricciardi, L; Fedele, R; Isola, S; Purello-D'Ambrosio, F


    We present the case of bronchospastic reaction to clarithromycin had during a drug challenge test. Personal allergic history was negative for respiratory allergies and positive for adverse drug reactions to general and regional anesthesia and to ceftriaxone. After the administration of 1/4 of therapeutic dose of clarithromycin the patient showed dyspnea, cough and bronchospasm in all the lung fields. The positivity of the test was confirmed by the negativity to the administration of placebo. The quickness and the clinical characteristic of the adverse reaction suggest a pathogenic mechanism of immediate-type hypersensitivity. On reviewing the literature we have found no reports of bronchospastic reaction to clarithromycin. Macrolides are a class of antibiotics mainly used in the last years in place of beta-lactams because of a broad spectrum of action and a low allergic power. In fact, there are few reports on allergic reactions to these molecules. Clarithromycin is one of the latest macrolides, characterised by the presence of a 14-carbon-atom lactone ring as erythromycin, active on a wide spectrum of pathogens.

  13. A MALDI-chip integrated system with a monitoring window

    Brivio, Monica; Tas, Niels R.; Goedbloed, Martijn H.; Gardeniers, Han J.G.E.; Verboom, Willem; Berg, van den Albert; Reinhoudt, David N.


    The integration of a monitoring port along the microfluidic path of a MALDI-chip integrated device is described. Optimization of the microreactor design allows longer reaction and measuring times. The Schiff base reaction between 4-tert-butylaniline ( 1) and 4-tert-butylbenzaldehyde ( 2) in ethanol

  14. Chemical kinetics of gas reactions

    Kondrat'Ev, V N


    Chemical Kinetics of Gas Reactions explores the advances in gas kinetics and thermal, photochemical, electrical discharge, and radiation chemical reactions. This book is composed of 10 chapters, and begins with the presentation of general kinetic rules for simple and complex chemical reactions. The next chapters deal with the experimental methods for evaluating chemical reaction mechanisms and some theories of elementary chemical processes. These topics are followed by discussions on certain class of chemical reactions, including unimolecular, bimolecular, and termolecular reactions. The rema

  15. Reaction Qualifications Revisited

    Lippert-Rasmussen, Kasper


    of merit. Specifically, it preserves symmetry between negative evaluations of antimeritocratic bases of selection and negative evaluations of qualifications rooted in comparable antimeritocratic reactions. So if employers should not select among applicants on the basis of their (the employers') racial...... preferences, recipients should not respond to the applicant actually hired on the basis of their (the recipients') racial preferences. My account decomposes the meritocratic ideal into four separate norms, one of which applies to recipients rather than to selectors. Finally, it defends the view that reaction...... reaction-qualifications are entirely irrelevant from the point of view of merit, the view expounded here implies that the ideal of meritocracy and the norm of non-discrimination are less closely tied than theorists like Andrew Mason and David Miller believe.  ...

  16. Nanoparticle Reactions on Chip

    Köhler, J. M.; Kirner, Th.; Wagner, J.; Csáki, A.; Möller, R.; Fritzsche, W.

    The handling of heterogenous systems in micro reactors is difficult due to their adhesion and transport behaviour. Therefore, the formation of precipitates and gas bubbles has to be avoided in micro reaction technology, in most cases. But, micro channels and other micro reactors offer interesting possibilities for the control of reaction conditions and transport by diffusion and convection due to the laminar flow caused by small Reynolds numbers. This can be used for the preparation and modification of objects, which are much smaller than the cross section of microchannels. The formation of colloidal solutions and the change of surface states of nano particles are two important tasks for the application of chip reactors in nanoparticle technology. Some concepts for the preparation and reaction of nanoparticles in modular chip reactor arrangements will be discussed.

  17. Inflammatory reaction in chondroblastoma

    Yamamura, Sigeki [Dept. of Orthopedic Surgery, Nagoya Univ. School of Medicine (Japan); Sato, Keiji [Dept. of Orthopedic Surgery, Nagoya Univ. School of Medicine (Japan); Sugiura, Hideshi [Dept. of Orthopedic Surgery, Nagoya Univ. School of Medicine (Japan); Iwata, Hisashi [Dept. of Orthopedic Surgery, Nagoya Univ. School of Medicine (Japan)


    The objective of this study was to evaluate the inflammatory reaction accompanying chondroblastoma and to define the value of the finding in clinical practice. We reviewed the clinical, radiographic, and magnetic resonance (MR) findings in six patients with histologically proven chondroblastoma. In all cases, MR imaging showered marrow and soft tissue edema. In four of six cases, periosteal reaction related to intra-osseous edema was more clearly demonstrated on MR imaging than on radiographs. Follow-up MR studies after surgery were available in three patients and all showed disappearance of inflammatory responses such as marrow and soft tissue edema, and reactive synovitis. We propose that these inflammatory reactions of chondroblastomas are inportant signs for detecting residual tumor in recurrences after surgery, as well as for making a precise diagnosis. The MR changes may also be valuable in demonstrating eradication of the tumor. (orig./MG)

  18. Hipersensitivity Reactions to Corticosteroids.

    Berbegal, L; DeLeon, F J; Silvestre, J F


    Corticosteroids are widely used drugs in the clinical practice, especially by topic application in dermatology. These substances may act as allergens and produce immediate and delayed hypersensitivity reactions. Allergic contact dermatitis is the most frequent presentation of corticosteroid allergy and it should be studied by patch testing in specific units. The corticosteroids included in the Spanish standard battery are good markers but not ideal. Therefore, if those makers are positive, it is useful to apply a specific battery of corticosteroids and the drugs provided by patients. Immediate reactions are relatively rare but potentially severe, and it is important to confirm the sensitization profile and to guide the use of alternative corticosteroids, because they are often necessary in several diseases. In this article we review the main concepts regarding these two types of hypersensitivity reactions in corticosteroid allergy, as well as their approach in the clinical practice. Copyright © 2015 Elsevier España, S.L.U. and AEDV. All rights reserved.

  19. Adverse reactions to cosmetics

    Dogra A


    Full Text Available Adverse reaction to cosmetics constitute a small but significant number of cases of contact dermatitis with varied appearances. These can present as contact allergic dermatitis, photodermatitis, contact irritant dermatitis, contact urticaria, hypopigmentation, hyperpigmentotion or depigmentation, hair and nail breakage. Fifty patients were included for the study to assess the role of commonly used cosmetics in causing adverse reactions. It was found that hair dyes, lipsticks and surprisingly shaving creams caused more reaction as compared to other cosmetics. Overall incidence of contact allergic dermatitis seen was 3.3% with patients own cosmetics. Patch testing was also done with the basic ingredients and showed positive results in few cases where casual link could be established. It is recommended that labeling of the cosmetics should be done to help the dermatologists and the patients to identify the causative allergen in cosmetic preparation.

  20. Volatility Measurements Of Reaction Chamber-Generated Particles

    Paulsen, D. [PSI and ETH Zuerich (Switzerland); Duplissy, J.; Weingartner, E.; Alfarra, R. [University of Manchester (United Kingdom); Baltensperger, U.


    A volatility-tandem differential mobility analyzer (VTDMA) was designed to monitor the non-volatile fraction of reaction chamber-generated organic particles. Using a coiled-tube heater for particle volatilization, particle volume fraction remaining measurements were made for wall temperatures of 100, 150, and 200 C. Oligomerization of organic particles generated from irradiations of {alpha}-pinene/NO{sub x} in the reaction chamber shows a strong linear relationship with time. (author)

  1. The Intersection of Interfacial Forces and Electrochemical Reactions


    We review recent developments in experimental techniques that simultaneously combine measurements of the interaction forces or energies between two extended surfaces immersed in electrolyte solutions - primarily aqueous - with simultaneous monitoring of their (electro)chemical reactions and controlling the electrochemical surface potential of at least one of the surfaces. Combination of these complementary techniques allows for simultaneous real time monitoring of angstrom level changes in su...

  2. Monitor resultaten geluid 2000

    Jabben J; Potma CJM; Swart WJR; LLO


    As part of an enhanced effort in monitoring the environmental quality in 1999, the RIVM set up a noise monitoring programme. This programme forms part of the project, "Development of a monitoring system for noise and disturbance", which aims at establishing a number of permanent sites for monitoring

  3. Knockout reactions: experimental aspects

    Cortina Gil, D. [Santiago de Compostela Univ. (Spain)


    The availability of radioactive beams has given rise to intense activity in the field of direct reactions. The removal of one(two)-nucleon (referred to as nucleon knockout in this text) from a fast exotic projectile has been extensively investigated. This lecture provides a general overview of the experimental results achieved using this technique. The sensitivity of the method to different experimental aspects is illustrated with a few examples. Special attention is given to the application of nucleon-knockout reactions as a general purpose spectroscopic tool. (author)

  4. 甲氨蝶呤治疗侵蚀性葡萄胎的血药浓度监测及不良反应观察%Monitoring drug concentration and adverse reactions of methotrexate in the treatment of invasive hydatidiform mole

    宁俊红; 吴志刚; 雷莹; 张若梅


    Objective:To investigate the necessity of monitoring methotrexate (MTX) concentration and its adverse reactions in the treatment of invasive hydatidiform mole. Methods:Ten patients diagnosed as invasive hydatidiform mole were given intramuscular methotrexate 0.4 mg·kg-1·d-1 at the same time every day for five days. Blood concentrations of methotrexate were determined at 24, 72, 120 hours after the first intramuscular injection and ADRs induced by MTX were observed. Results:After one or more cycles of treatment, nine patients were cured, one patient changed the chemotherapy due to poor efficacy. Methotrexate concentrations in thirty plasma from ten patients were lower than the safety value. ADRs occurred in six patients including one patient with severe bone marrow suppression. Conclusion:It's not necessary to monitor methotrexate blood concentration in the treatment of invasive hydatidiform mole and use calcium folinate for ADRs. Although the plasma concentration was very low, ADRs induced by methotrexate should be paid more attention to.%  目的:探讨甲氨蝶呤治疗侵蚀性葡萄胎时,监测其血药浓度的必要性及不良反应的发生情况.方法:10例确诊为侵蚀性葡萄胎的患者,肌注甲氨蝶呤0.4 mg·kg-1·d-1,每天同一时间肌注,连续肌注5 d,并于第一次肌注后的24,72,120 h取2 mL静脉血,测定甲氨蝶呤的血药浓度,同时观察不良反应.结果:经过一个或多个周期的治疗后,9名患者治愈,1名患者由于疗效不佳,改用其他化疗方案.10例患者共30份甲氨蝶呤的血药浓度值均低于安全值;10例患者中,6例出现不良反应,其中1例患者出现严重的骨髓抑制.结论:治疗侵蚀性葡萄胎时,监测甲氨蝶呤血药浓度的意义不大,没有必要用四氢叶酸钙解毒;甲氨蝶呤的血药浓度很低时,仍然需要关注其所致的不良反应.

  5. 质谱智能选择反应监测用于蛋白质绝对定量中母子离子对确证的方法研究%Validation of Transitions by Intelligent Selected Reaction MonitoringMass Spectrometry for Protein Absolute Quantitation

    卫军营; 张养军; 赵炎; 陈希曙; 马岩; 应万涛; 钱小红


    Selected reaction monitoring (SRM)-mass spectrometry is increasingly applied to absolute quantitation of proteins. In large scale quantitative analyses, one of the main challenges is that the initial set of transitions should be optimized and validated to ensure that the quantified signals indeed derive from the targeted peptide. SRM-triggered MS/MS acquisition is an efficient way for validation, but still needs improvement. Recently, an innovative intelligent SRM (Isrm) was introduced to alleviate the challenge. In this study, iSRM was tested to validate the transitions of peptides of bovine serum albumin (BSA) and yeast proteins. The experimental results show that the method has increased selectivity and throughput for validation of transitions of peptides. Even for 1 fmol BSA, a set of transitions can be successfully validated, indicating that iSRM method is suitable for large scale validation of transitions of peptides in quantitative proteomics research.%质谱选择反应监测(SRM)技术在蛋白质绝对定量分析中的应用越来越广泛,其成功应用的关键是肽段母子离子对的正确选择与确证.触发采集二级图谱是目前常用的母子离子对确认方法,但分析效率有待于提高.质谱智能选择反应监测(iSRM)是新近发展的高通量分析方法.为了考察该方法用于通量化母子离子对确证时的效果,选用牛血清白蛋白(BSA)和酵母蛋白提取物作为样品进行分析.结果表明,该方法具有更高的分析灵敏度,可以对低至1 fmol BSA样品中的母子离子对进行确证,而且相对于触发采集二级图谱方法而言,具有更高的分析通量,为规模化母子离子对选择与确证提供了一种新的策略.

  6. Enantioselective Vinylogous Organocascade Reactions.

    Hepburn, Hamish B; Dell'Amico, Luca; Melchiorre, Paolo


    Cascade reactions are powerful tools for rapidly assembling complex molecular architectures from readily available starting materials in a single synthetic operation. Their marriage with asymmetric organocatalysis has led to the development of novel techniques, which are now recognized as reliable strategies for the one-pot enantioselective synthesis of stereochemically dense molecules. In recent years, even more complex synthetic challenges have been addressed by applying the principle of vinylogy to the realm of organocascade catalysis. The key to the success of vinylogous organocascade reactions is the unique ability of the chiral organocatalyst to transfer reactivity to a distal position without losing control on the stereo-determining events. This approach has greatly expanded the synthetic horizons of the field by providing the possibility of forging multiple stereocenters in remote positions from the catalyst's point of action with high selectivity, while simultaneously constructing multiple new bonds. This article critically describes the developments achieved in the field of enantioselective vinylogous organocascade reactions, charting the ideas, the conceptual advances, and the milestone reactions that have been essential for reaching highly practical levels of synthetic efficiency.

  7. Explaining competitive reaction effects

    Leeflang, P.S.H.; Wittink, D.R.

    Changes in promotional expenditure decisions for a brand, as in other marketing decisions, should be based on the expected impact on purchase and consumption behavior as well as on the likely reactions by competitors. Purchase behavior may be predicted from estimated demand functions. Competitive

  8. Reaction product imaging

    Chandler, D.W. [Sandia National Laboratories, Livermore, CA (United States)


    Over the past few years the author has investigated the photochemistry of small molecules using the photofragment imaging technique. Bond energies, spectroscopy of radicals, dissociation dynamics and branching ratios are examples of information obtained by this technique. Along with extending the technique to the study of bimolecular reactions, efforts to make the technique as quantitative as possible have been the focus of the research effort. To this end, the author has measured the bond energy of the C-H bond in acetylene, branching ratios in the dissociation of HI, the energetics of CH{sub 3}Br, CD{sub 3}Br, C{sub 2}H{sub 5}Br and C{sub 2}H{sub 5}OBr dissociation, and the alignment of the CD{sub 3} fragment from CD{sub 3}I photolysis. In an effort to extend the technique to bimolecular reactions the author has studied the reaction of H with HI and the isotopic exchange reaction between H and D{sub 2}.

  9. Cluster knockout reactions

    Arun K Jain; B N Joshi


    Cluster knockout reactions are expected to reveal the amount of clustering (such as that of , d and even of heavier clusters such as 12C, 16O etc.) in the target nucleus. In simple terms, incident medium high-energy nuclear projectile interacts strongly with the cluster (present in the target nucleus) as if it were existing as a free entity. Theoretically, the relatively softer interactions of the two outgoing particles with the residual nucleus lead to optical distortions and are treated in terms of distorted wave (DW) formalism. The long-range projectile–cluster interaction is accounted for, in terms of the finite range (FR) direct reaction formalism, as against the more commonly adopted zero-range (ZR) distorted wave impulse approximation (DWIA) formalism. Comparison of the DWIA calculations with the observed data provide information about the momentum distribution and the clustering spectroscopic factor of the target nucleus. Interesting results and some recent advancements in the area of (, 2) reactions and heavy cluster knockout reactions are discussed. Importance of the finite-range vertex and the final-state interactions are brought out.

  10. Reaction Formulation: A Bibliography.

    Pedrini, D. T.; Pedrini, Bonnie C.

    Reaction formation was studied by Sigmund Freud. This defense mechanism may be related to repression, substitution, reversal, and compensation (or over-compensation). Alfred Adler considered compensation a basic process in his individual psychology. Anna Freud discussed some defense mechanisms, and Bibring, Dwyer, Huntington, and Valenstein…

  11. Explaining competitive reaction effects

    Leeflang, P.S.H.; Wittink, D.R.


    Changes in promotional expenditure decisions for a brand, as in other marketing decisions, should be based on the expected impact on purchase and consumption behavior as well as on the likely reactions by competitors. Purchase behavior may be predicted from estimated demand functions. Competitive re

  12. HF Chain Reaction Laser


    reaction can develop uni2ormly in a subsonic flow with snall teemperatiu-e rise over a distance much longer than the time for mixing, thus tendiný to isolate...upper level population, moreover, the observed effects of H2, Tabla 3, appear to be predicted reasonably well by the model. In the calcula- tions 112

  13. Reactions of Negative Ions


    2 + H2 SO 4 + HS04 (HNO 3 ) 2 + HNO 3 1.1 0.6 * defined as 1 The most important results from an atmospheric viewpoint are the reactions of H SO with NO...constant HS04 >4.5 bracketing 22 0 C1 , 1.95 * 0.25 bracketlng 32 -4 __.. . .___,_=____,,_______... . . . -- . . . . One particularly interesting aspect of

  14. The Gewald multicomponent reaction

    Huang, Yijun; Doemling, Alexander


    The Gewald reaction of sulfur, cyanoacetic acid derivatives, and oxo-component (G-3CR) yielding highly substituted 2-aminothiophene derivatives has seen diverse applications in combinatorial and medicinal chemistry. Its products are of great use in pharmaceutical industry mainly as small molecular w




    Full Text Available OBJECTIVES: Physical exercise provides multiple benefits to an individual. It is known that exercising regularly can prevent coronary heart disease, hypertension and obesity and improve flexibility. The effect of exercise on visual reaction time needs to be studied, a s the existing data on the benefit of aerobic exercise on psychomotor functions is insufficient. MATERIALS AND METHODS: Online Visual reaction time is measured before and after exercise. Subjects were instructed to run on the spot with a springy step in ex aggerated motion for 50 to 60 counts at 2 counts per second, maintaining a constant rhythm. RESULTS: We observed that reaction time was significantly lower after performance of exercise. Individuals reported improved mental alertness, feel good factor, bet ter mood and increase circulation. CONCLUSION: Improving reaction times in sports can help the athlete to optimize his performance in making decisions and increasing attention span for example getting off the starting blocks sooner or successfully making c ontact with the ball. In addition this study shows that use of physical exercise helps improve cognitive function. Exercise proves to be a cheap non pharmacological alternative to improve cognitive performance.

  16. The human acrosome reaction

    H.W.G.Baker; D.Y.Liu; C.Garrett; M.Martic


    We developed tests of sperm-oocyte interaction: sperm-zona binding, zona-induced acrosome reaction, spermzona penetration and sperm-oolemma binding, using oocytes which failed to fertilise in clinical in vitro fertilization (IVF). Although oocyte defects contribute to failure of sperm oocyte interaction, rarely are all oocytes from one woman affected. Low or zero fertilization in standard IVFwas usually caused by sperm abnormalities. Poor sperm-zona pellucida binding was frequently associated with failure of standard IVF and obvious defects of sperm motility or morphology. The size and shape of the acrosome is particularly important for sperm binding to the oocyte. The proportion of acrosome intact sperm in the insemination medium was related to the IVF rate. Inducing the acrosome reaction with a calcium ionophore reduced sperm-zona binding. Blocking acrosome dispersal with an acrosin inhibitor prevented spermzona penetration. Sperm-zona penetration was even more highly related to IVF rates than was sperm-zona binding. Some patients had low or zero fertilization rates with standard IVF but normal sperm by conventional tests and normal sperm-zona binding. Few of their sperm underwent the acrosome reaction on the surface of the zona and none penetrated the zona. In contrast, fertilization and pregnancy rates were high with intracytoplasmic sperm injection. We call thiscondition defective zona pellucida induced acrosome reaction. Discovery of the nature of the abnormalities in the signal transduction and effector pathways of the human zona pellucida induced acrosome reaction should result in simpler tests and treatments for the patients and also provide new leads for contraceptive development.

  17. Inorganic Reaction Mechanisms. Part I

    Cooke, D. O.


    Provides a collection of data on the mechanistic aspects of inorganic chemical reactions. Wherever possible includes procedures for classroom demonstration or student project work. The material covered includes gas phase reactions, reactions in solution, mechanisms of electron transfer, the reaction between iron III and iodine, and hydrolysis. (GS)

  18. Severe infusion reaction induced by trastuzumab: a case report.

    Tada, Keiichiro; Ito, Yoshinori; Hatake, Kiyohiko; Okudaira, Taeko; Watanabe, Jun-ichiro; Arakawa, Masahiro; Miyazato, Masayo; Irie, Tetsuya; Mizunuma, Nobuyuki; Takahashi, Syunji; Aiba, Keisuke; Horikoshi, Noboru; Kasumi, Fujio


    We report a case of a severe infusion reaction caused by trastuzumab. A 59-year-old woman with metastatic breast cancer was treated with trastuzumab. During the first infusion, initial symptoms such as severe headache and general fatigue developed. Blood pressure fell 90 minutes after these initial symptoms. A collapsed lung was demonstrated by chest X-ray and computed tomography. Steroid therapy was successfully used for these reactions. Careful monitoring of vital signs, examination of the respiratory system, and the use of steroids are recommended for severe infusion reaction.

  19. Contactless optoelectronic technique for monitoring epoxy cure.

    Cusano, A; Buonocore, V; Breglio, G; Calabrò, A; Giordano, M; Cutolo, A; Nicolais, L


    We describe a novel noninvasive optical technique to monitor the refractive-index variation in an epoxy-based resin that is due to the polymerization process. This kind of resin is widely used in polymer matrix composites. It is well known that the process of fabricating a thermoset-based composite involves mass and heat transfer coupled with irreversible chemical reactions that induce physical changes. To improve the quality and the reliability of these materials, monitoring the cure and optimization of the manufacturing process are of key importance. We discuss the basic operating principles of an optical system based on angle deflection measurements and present typical cure-monitoring results obtained from optical characterization. The method provides a flexible, high-sensitivity, material-independent, low-cost, noninvasive tool for monitoring real-time refractive-index variation.

  20. Spin distribution in neutron induced preequilibrium reactions

    Dashdorj, D; Kawano, T; Chadwick, M; Devlin, M; Fotiades, N; Nelson, R O; Mitchell, G E; Garrett, P E; Agvaanluvsan, U; Becker, J A; Bernstein, L A; Macri, R; Younes, W


    The preequilibrium reaction mechanism makes an important contribution to neutron-induced reactions above E{sub n} {approx} 10 MeV. The preequilibrium process has been studied exclusively via the characteristic high energy neutrons produced at bombarding energies greater than 10 MeV. They are expanding the study of the preequilibrium reaction mechanism through {gamma}-ray spectroscopy. Cross-section measurements were made of prompt {gamma}-ray production as a function of incident neutron energy (E{sub n} = 1 to 250 MeV) on a {sup 48}Ti sample. Energetic neutrons were delivered by the Los Alamos National Laboratory spallation neutron source located at the Los Alamos Neutron Science Center facility. The prompt-reaction {gamma} rays were detected with the large-scale Compton-suppressed Germanium Array for Neutron Induced Excitations (GEANIE). Neutron energies were determined by the time-of-flight technique. The {gamma}-ray excitation functions were converted to partial {gamma}-ray cross sections taking into account the dead-time correction, target thickness, detector efficiency and neutron flux (monitored with an in-line fission chamber). Residual state population was predicted using the GNASH reaction code, enhanced for preequilibrium. The preequilibrium reaction spin distribution was calculated using the quantum mechanical theory of Feshback, Kerman, and Koonin (FKK). The multistep direct part of the FKK theory was calculated for a one-step process. The FKK preequilibrium spin distribution was incorporated into the GNASH calculations and the {gamma}-ray production cross sections were calculated and compared with experimental data. The difference in the partial {gamma}-ray cross sections using spin distributions with and without preequilibrium effects is significant.

  1. Curing Reaction Model of Epoxy Asphalt Binder

    QIAN Zhendong; CHEN Leilei; WANG Yaqi; SHEN Jialin


    In order to understand the strength developing law of the epoxy asphalt mixture,a curing reaction model of the epoxy asphalt binder was proposed based upon the thermokinetic analysis.Given some assumptions,the model was developed by applying the Kissinger law as well as Arrhenius equation,and the differential scanning calorimetry was performed for estimating the model parameters.To monitor the strength development of the epoxy asphalt mixture,a strength test program was employed and then results were compared to those produced from the proposed model.The comparative evaluation shows that a good consistency exists between the outputs from test program and the proposed model,indicating that the proposed model can be used effectively for simulating the curing reaction process for the epoxy asphalt binder and predicting the strength development for the epoxy asphalt mixture.

  2. Hydrogenation reactions in interstellar CO ice analogues

    Fuchs, G W; Ioppolo, S; Romanzin, C; Bisschop, S E; Andersson, S; Van Dishoeck, E F; Linnartz, H


    Hydrogenation reactions of CO in inter- and circumstellar ices are regarded as an important starting point in the formation of more complex species. Previous laboratory measurements by two groups on the hydrogenation of CO ices resulted in controversial results on the formation rate of methanol. Our aim is to resolve this controversy by an independent investigation of the reaction scheme for a range of H-atom fluxes and different ice temperatures and thicknesses. Reaction rates are determined by using a state-of-the-art ultra high vacuum experimental setup to bombard an interstellar CO ice analog with room temperature H atoms. The reaction of CO + H into H2CO and subsequently CH3OH is monitored by a Fourier transform infrared spectrometer in a reflection absorption mode. In addition, after each completed measurement a temperature programmed desorption experiment is performed to identify the produced species. Different H-atom fluxes, morphologies, and ice thicknesses are tested. The formation of both formaldeh...

  3. Molecular beam studies of reaction dynamics

    Lee, Y.T. [Lawrence Berkeley Laboratory, CA (United States)


    The major thrust of this research project is to elucidate detailed dynamics of simple elementary reactions that are theoretically important and to unravel the mechanism of complex chemical reactions or photochemical processes that play important roles in many macroscopic processes. Molecular beams of reactants are used to study individual reactive encounters between molecules or to monitor photodissociation events in a collision-free environment. Most of the information is derived from measurement of the product fragment energy, angular, and state distributions. Recent activities are centered on the mechanisms of elementary chemical reactions involving oxygen atoms with unsaturated hydrocarbons, the dynamics of endothermic substitution reactions, the dependence of the chemical reactivity of electronically excited atoms on the alignment of excited orbitals, the primary photochemical processes of polyatomic molecules, intramolecular energy transfer of chemically activated and locally excited molecules, the energetics of free radicals that are important to combustion processes, the infrared-absorption spectra of carbonium ions and hydrated hydronium ions, and bond-selective photodissociation through electric excitation.

  4. Enzyme Reactions in Nanoporous, Picoliter Volume Containers

    Siuti, Piro; Retterer, Scott T.; Choi, Chang-Kyoung; Doktycz, Mitchel J.


    Advancements in nanoscale fabrication allow creation of small volume reaction containers that can facilitate the screening and characterization of enzymes. A porous, ~19 pL volume vessel has been used in this work to carry out enzyme reactions under varying substrate concentrations. Assessment of small molecule and Green Fluorescent Protein diffusion from the vessels indicates that pore sizes on order of 10 nm can be obtained, allowing capture of proteins and diffusive exchange of small molecules. Glucose oxidase and horseradish peroxidase can be contained in these structures and diffusively fed with a solution containing glucose and the fluorogenic substrate Amplex Red™ through the engineered nanoscale pore structure. Fluorescent microscopy was used to monitor the reaction, which was carried out under microfluidic control. Kinetic characteristics of the enzyme (Km and Vmax) were evaluated and compared with results from conventional scale reactions. These picoliter, nanoporous containers can facilitate quick determination of enzyme kinetics in microfluidic systems without the requirement of surface tethering and can be used for applications in drug discovery, clinical diagnostics and high-throughput screening. PMID:22148720

  5. Reaction chemistry of cerium



    It is truly ironic that a synthetic organic chemist likely has far greater knowledge of the reaction chemistry of cerium(IV) than an inorganic colleague. Cerium(IV) reagents have long since been employed as oxidants in effecting a wide variety of organic transformations. Conversely, prior to the late 1980s, the number of well characterized cerium(IV) complexes did not extend past a handful of known species. Though in many other areas, interest in the molecular chemistry of the 4f-elements has undergone an explosive growth over the last twenty years, the chemistry of cerium(IV) has for the most part been overlooked. This report describes reactions of cerium complexes and structure.

  6. Reaction chemistry of cerium



    It is truly ironic that a synthetic organic chemist likely has far greater knowledge of the reaction chemistry of cerium(IV) than an inorganic colleague. Cerium(IV) reagents have long since been employed as oxidants in effecting a wide variety of organic transformations. Conversely, prior to the late 1980s, the number of well characterized cerium(IV) complexes did not extend past a handful of known species. Though in many other areas, interest in the molecular chemistry of the 4f-elements has undergone an explosive growth over the last twenty years, the chemistry of cerium(IV) has for the most part been overlooked. This report describes reactions of cerium complexes and structure.

  7. Photooxidative reactions of psoralens

    Potapenko, A.Ya.; Sukhorukov, V.L. (Vtoroj Moskovskij Gosudarstvennyj Meditsinskij Inst. (USSR))


    The mechanism and biological significance of photooxidative reactions of psoralens are reviewed. Skin-photosensitizing activities of bifunctional and monofunctional psoralens are compared. Antioxidants tocopherols and butilated hydroxytoluene inhibit photochemical reactions of psoralens responsible for induction of erythema. The same antioxidants do not inhibit PUVA-therapy of psriasis. Though psoralens can generate singlet oxygen under UVA-irradiation (315 - 400 nm), nevertheless singlet oxygen does not play a significant role in 8-methoxypsoralen (8-MOP) sensitized photooxidation of tocopherol or dihydroxyphenylalanine (DOPA). SH-compounds enhance the rate of 8-MOP sensitized photooxidation of DOPA by a factor of four, simultaneously the rate of oxidation of SH-groups is enhanced many fold in the presence of DOPA. Under UVA-irradiation in organic solvents psoralens are photooxidized. Dimeric photooxidized psoralens are easily destructed in water medium, their destruction induce oxidation of unsaturated lipids and DOPA.

  8. How reaction and permeability develop in dehydrating systems

    Leclère, H. J.; Faulkner, D. R.; Wheeler, J.; Bedford, J. D.


    The triggering of earthquakes at intermediate-depth along subduction zones is often explained by dehydration reactions, releasing free-water and allowing pore-fluid pressure build-up. During dehydration reactions, pore-fluid pressure is increased when permeability is low enough to prevent fluid escape. Permeability is not constant during dehydration reactions but is rather changed by porosity changes (i.e. solid volume reduction or pore compaction). The evolution of permeability during dehydration reactions will thus dictate the pore-fluid pressure evolution that will affect rock strength and earthquake triggering. However, our understanding on the coupling between permeability, pore-fluid pressure, microstructures, deformation and reaction rate is incomplete. In some cases, the development of reactions is distributed uniformly and permeability increases steadily throughout the reaction progress. In other cases, reactions will not proceed uniformly and nature along with previous experiments indicate that "reaction fronts" develop. On the large scale, reaction rate and fluid pressure evolution depend on the movement of these fronts. Experimental results are presented on permeability and reaction front evolution during gypsum dehydration - an analogue for silicate dehydration. Triaxial experiments were conducted using polycrystalline gypsum cores with very low initial porosity. Pore-fluid pressure is controlled at one end of the sample and monitored at the other in order to measure permeability. Gypsum cores were dehydrated at a constant temperature of 115°C. Two parameter spaces were explored: the pore-fluid pressure (20, 40 or 60 MPa) that influences reaction rate, and effective confining pressure (60 or 110 MPa) that influences pore-compaction. The evolution of permeability, porosity, reaction rate and pore-fluid pressure are measured throughout the reaction. SEM observations of post-mortem samples collected at three key stages during the reaction shows how the

  9. Photochemical reaction dynamics

    Moore, B.C. [Lawrence Berkeley Laboratory, Livermore, CA (United States)


    The purpose of the program is to develop a fundamental understanding of unimolecular and bimolecular reaction dynamics with application in combustion and energy systems. The energy dependence in ketene isomerization, ketene dissociation dynamics, and carbonyl substitution on organometallic rhodium complexes in liquid xenon have been studied. Future studies concerning unimolecular processes in ketene as well as energy transfer and kinetic studies of methylene radicals are discussed.

  10. Complex kinetics of a Landolt-type reaction: the later phase of the thiosulfate-iodate reaction.

    Varga, Dénes; Nagypál, István; Horváth, Attila K


    The thiosulfate-iodate reaction has been studied spectrophotometrically in slightly acidic medium at 25.0 +/- 0.1 degrees C in acetate/acetic acid buffer by monitoring the absorbance at 468 nm at the isosbestic point of iodine-triiodide ion system. The formation of iodine after the Landolt time follows a rather complex kinetic behavior depending on the pH and on the concentration of the reactants as well. It is shown that the key intermediate of the reaction is I(2)O(2), its equilibrium formation from the well-known Dushman reaction along with their further reactions followed by subsequent reactions of HOI, HIO(2), S(2)O(3)OH(-), and S(2)O(3)I(-) adequately accounts for all the experimentally measured characteristics of the kinetic curves. A 19-step kinetic model is proposed and discussed with 13 fitted and 7 fixed parameters in detail.

  11. Blazar Monitoring List

    National Aeronautics and Space Administration — This is a compilation of sources in major blazar monitoring programs. This list contains all blazars known to be regularly monitored, plus all the MOJAVE- &...

  12. Lunar Health Monitor Project

    National Aeronautics and Space Administration — During the Phase II Lunar Health Monitor program, Orbital Research will develop a second generation wearable sensor suite for astronaut physiologic monitoring. The...

  13. Inductive Monitoring System (IMS)

    National Aeronautics and Space Administration — IMS: Inductive Monitoring System The Inductive Monitoring System (IMS) is a tool that uses a data mining technique called clustering to extract models of normal...

  14. Flight Systems Monitor Project

    National Aeronautics and Space Administration — This SBIR Phase I project will develop the Flight System Monitor which will use non-intrusive electrical monitoring (NEMO). The electronic system health of...

  15. Spacecraft Power Monitor Project

    National Aeronautics and Space Administration — This SBIR Phase I project will develop the Spacecraft Power Monitor (SPM) which will use non-intrusive electrical monitoring (NEMO). NEMO transforms the power...

  16. Biological Monitoring Team

    US Fish and Wildlife Service, Department of the Interior — The Biological Monitoring Team (BMT) was a pilot project focused on addressing NWRS inventory and monitoring needs in Regions 3 and 5. The BMT was a precursor to the...

  17. Apnea monitor (image)

    An apnea monitor checks the heart rate and respiration of the baby to make sure he or she is ... When either one falls below normal levels, the apnea monitor beeps to notify the care provider that ...

  18. Expertise and responsibility effects on pilots' reactions to flight deck alerts in a simulator.

    Zheng, Yiyuan; Lu, Yanyu; Yang, Zheng; Fu, Shan


    Flight deck alerts provide system malfunction information designed to lead corresponding pilot reactions aimed at guaranteeing flight safety. This study examined the roles of expertise and flight responsibility and their relationship to pilots' reactions to flight deck alerts. There were 17 pilots composing 12 flight crews that were assigned into pairs according to flight hours and responsibilities. The experiment included 9 flight scenarios and was carried out in a CRJ-200 flight simulator. Pilot performance was recorded by a wide angle video camera, and four kinds of reactions to alerts were defined for analysis. Pilots tended to have immediate reactions to uninterrupted cautions, with a turning off rate as high as 75%. However, this rate decreased sharply when pilots encountered interrupted cautions and warnings; they also exhibited many wrong reactions to warnings. Pilots with more expertise had more reactions to uninterrupted cautions than those with less expertise, both as pilot flying and pilot monitoring. Meanwhile, the pilot monitoring, regardless of level of expertise, exhibited more reactions than the pilot flying. In addition, more experienced pilots were more likely to have wrong reactions to warnings while acting as the monitoring pilot. These results suggest that both expertise and flight responsibility influence pilots' reactions to alerts. Considering crew pairing strategy, when a pilot flying is a less experienced pilot, a more experience pilot is suggested to be the monitoring pilot. The results of this study have implications for understanding pilots' behaviors to flight deck alerts, calling for specialized training and design of approach alarms on the flight deck.

  19. Environmental monitoring lecture notes

    Soldat, J.K.


    Criteria for environmental monitoring programs for radioactivity are presented. Standards for public exposure and the basis for maximum permissible concentration values are discussed. The value of pre-operational surveys, operation surveys, and emergency surveys in environmental monitoring programs is considered. The environmental monitoring program at the Hanford Area is described. 90 references.

  20. Inside the Monitor Model

    Carl, Michael; Dragsted, Barbara


    a “monitor model” according to which translators start with a literal default rendering procedure and where a monitor interrupts the default procedure when a problem occurs. This paper suggests an extension of the monitor model in which comprehension and production are processed in parallel by the default...

  1. Life Span Differences in Electrophysiological Correlates of Monitoring Gains and Losses during Probabilistic Reinforcement Learning

    Hammerer, Dorothea; Li, Shu-Chen; Muller, Viktor; Lindenberger, Ulman


    By recording the feedback-related negativity (FRN) in response to gains and losses, we investigated the contribution of outcome monitoring mechanisms to age-associated differences in probabilistic reinforcement learning. Specifically, we assessed the difference of the monitoring reactions to gains and losses to investigate the monitoring of…

  2. Well sealing via thermite reactions

    Lowry, William Edward; Dunn, Sandra Dalvit


    A platform is formed in a well below a target plug zone by lowering a thermite reaction charge into the well and igniting it, whereby the products of the reaction are allowed to cool and expand to form a platform or support in the well. A main thermite reaction charge is placed above the platform and ignited to form a main sealing plug for the well. In some embodiments an upper plug is formed by igniting an upper thermite reaction charge above the main thermite reaction charge. The upper plug confines the products of ignition of the main thermite reaction charge.

  3. BPA genetic monitoring - BPA Genetic Monitoring Project

    National Oceanic and Atmospheric Administration, Department of Commerce — Initiated in 1989, this study monitors genetic changes associated with hatchery propagation in multiple Snake River sub-basins for Chinook salmon and steelhead. We...

  4. Insect bite reactions

    Sanjay Singh


    Full Text Available Insects are a class of living creatures within the arthropods. Insect bite reactions are commonly seen in clinical practice. The present review touches upon the medically important insects and their places in the classification, the sparse literature on the epidemiology of insect bites in India, and different variables influencing the susceptibility of an individual to insect bites. Clinical features of mosquito bites, hypersensitivity to mosquito bites Epstein-Barr virus NK (HMB-EBV-NK disease, eruptive pseudoangiomatosis, Skeeter syndrome, papular pruritic eruption of HIV/AIDS, and clinical features produced by bed bugs, Mexican chicken bugs, assassin bugs, kissing bugs, fleas, black flies, Blandford flies, louse flies, tsetse flies, midges, and thrips are discussed. Brief account is presented of the immunogenic components of mosquito and bed bug saliva. Papular urticaria is discussed including its epidemiology, the 5 stages of skin reaction, the SCRATCH principle as an aid in diagnosis, and the recent evidence supporting participation of types I, III, and IV hypersensitivity reactions in its causation is summarized. Recent developments in the treatment of pediculosis capitis including spinosad 0.9% suspension, benzyl alcohol 5% lotion, dimethicone 4% lotion, isopropyl myristate 50% rinse, and other suffocants are discussed within the context of evidence derived from randomized controlled trials and key findings of a recent systematic review. We also touch upon a non-chemical treatment of head lice and the ineffectiveness of egg-loosening products. Knockdown resistance (kdr as the genetic mechanism making the lice nerves insensitive to permethrin is discussed along with the surprising contrary clinical evidence from Europe about efficacy of permethrin in children with head lice carrying kdr-like gene. The review also presents a brief account of insects as vectors of diseases and ends with discussion of prevention of insect bites and some

  5. Organocatalytic Enantioselective Henry Reactions

    Raquel P. Herrera


    Full Text Available A large number of interesting organocatalytic enantioselective protocols have been explored and successfully applied in the last decade. Among them, the Henry (nitroaldol reaction represents a powerful carbon-carbon bond-forming procedure for the preparation of valuable synthetic intermediates, such as enantioenriched nitro alcohols, which can be further transformed in a number of important nitrogen and oxygen-containing compounds. This area of research is still in expansion and a more complex version of this useful process has recently emerged, the domino Michael/Henry protocol, affording highly functionalized cycles with multiple stereogenic centers.

  6. Multispecies pair annihilation reactions.

    Deloubrière, Olivier; Hilhorst, Henk J; Täuber, Uwe C


    We consider diffusion-limited reactions A(i)+A(j)--> (12 and d> or =2, we argue that the asymptotic density decay for such mutual annihilation processes with equal rates and initial densities is the same as for single-species pair annihilation A+A-->. In d=1, however, particle segregation occurs for all q< infinity. The total density decays according to a q dependent power law, rho(t) approximately t(-alpha(q)). Within a simplified version of the model alpha(q)=(q-1)/2q can be determined exactly. Our findings are supported through Monte Carlo simulations.

  7. Low Energy Nuclear Reactions?

    CERN. Geneva; Faccini, R.


    After an introduction to the controversial problem of Low Energy Nuclear Reactions (LENR) catalyzed by neutrons on metallic hydride surfaces we present the results of an experiment, made in collaboration with ENEA Labs in Frascati, to search neutrons from plasma discharges in electrolytic cells. The negative outcome of our experiment goes in the direction of ruling out those theoretical models expecting LENR to occur in condensed matter systems under specific conditions. Our criticism on the theoretical foundations of such models will also be presented.

  8. Nuclear reactor effluent monitoring

    Minns, J.L.; Essig, T.H. [Nuclear Regulatory Commission, Washington, DC (United States)


    Radiological environmental monitoring and effluent monitoring at nuclear power plants is important both for normal operations, as well as in the event of an accident. During normal operations, environmental monitoring verifies the effectiveness of in-plant measures for controlling the release of radioactive materials in the plant. Following an accident, it would be an additional mechanism for estimating doses to members of the general public. This paper identifies the U.S. Nuclear Regulatory Commission (NRC) regulatory basis for requiring radiological environmental and effluent monitoring, licensee conditions for effluent and environmental monitoring, NRC independent oversight activities, and NRC`s program results.

  9. Organic chemistry: Reactions triggered electrically

    Xiang, Limin; Tao, N. J.


    Single-molecule experiments have revealed that chemical reactions can be controlled using electric fields -- and that the reaction rate is sensitive to both the direction and the strength of the applied field. See Letter p.88

  10. Environmental Monitoring Plan

    Holland, R.C. [Science Applications International Corp., San Diego, CA (United States)


    This Environmental Monitoring Plan was written to fulfill the requirements of Department of Energy (DOE) Order 5400.1 and DOE Environmental Regulatory Guide DOE/EH 0173T. This Plan documents the background, organizational structure, and methods used for effluent monitoring and environmental surveillance at Sandia National Laboratories/California. The design, rationale, and historical results of the environmental monitoring system are discussed in detail. Throughout the Plan, recommendations for improvements to the monitoring system are made. This revision to the Environmental Monitoring Plan was written to document the changes made to the Monitoring Program during 1992. Some of the data (most notably the statistical analyses of past monitoring data) has not been changed.

  11. Theoretical Studies of Reaction Surfaces


    Similar levels of agreement are being found in studies of water clusters12 , the Menshutkin reaction 13 (ion separation reaction ), a prototypical SN2 ...of both reactants and products. These analyses reveal that Bery pseudorotation occurs repeatedly during the side attack, whereas the SN2 reaction H...31 Aug 97 4. TITLE AND SUBTITLE 5. FUNDING NUMBERS AASERT93 THEORETICAL STUDIES OF REACTION SURFACES F49620-93-1-0556 3484/XS 6. AUTHOR(S) 61103D DR

  12. Orbital Energy-Based Reaction Analysis of SN2 Reactions

    Takao Tsuneda


    Full Text Available An orbital energy-based reaction analysis theory is presented as an extension of the orbital-based conceptual density functional theory. In the orbital energy-based theory, the orbitals contributing to reactions are interpreted to be valence orbitals giving the largest orbital energy variation from reactants to products. Reactions are taken to be electron transfer-driven when they provide small variations for the gaps between the contributing occupied and unoccupied orbital energies on the intrinsic reaction coordinates in the initial processes. The orbital energy-based theory is then applied to the calculations of several S N2 reactions. Using a reaction path search method, the Cl− + CH3I → ClCH3 + I− reaction, for which another reaction path called “roundabout path” is proposed, is found to have a precursor process similar to the roundabout path just before this SN2 reaction process. The orbital energy-based theory indicates that this precursor process is obviously driven by structural change, while the successor SN2 reaction proceeds through electron transfer between the contributing orbitals. Comparing the calculated results of the SN2 reactions in gas phase and in aqueous solution shows that the contributing orbitals significantly depend on solvent effects and these orbitals can be correctly determined by this theory.

  13. Mass Transfer with Chemical Reaction.

    DeCoursey, W. J.


    Describes the organization of a graduate course dealing with mass transfer, particularly as it relates to chemical reactions. Discusses the course outline, including mathematics models of mass transfer, enhancement of mass transfer rates by homogeneous chemical reaction, and gas-liquid systems with chemical reaction. (TW)

  14. Mass Transfer with Chemical Reaction.

    DeCoursey, W. J.


    Describes the organization of a graduate course dealing with mass transfer, particularly as it relates to chemical reactions. Discusses the course outline, including mathematics models of mass transfer, enhancement of mass transfer rates by homogeneous chemical reaction, and gas-liquid systems with chemical reaction. (TW)

  15. Plasmonic smart dust for probing local chemical reactions.

    Tittl, Andreas; Yin, Xinghui; Giessen, Harald; Tian, Xiang-Dong; Tian, Zhong-Qun; Kremers, Christian; Chigrin, Dmitry N; Liu, Na


    Locally probing chemical reactions or catalytic processes on surfaces under realistic reaction conditions has remained one of the main challenges in materials science and heterogeneous catalysis. Where conventional surface interrogation techniques usually require high-vacuum conditions or ensemble average measurements, plasmonic nanoparticles excel in extreme light focusing and can produce highly confined electromagnetic fields in subwavelength volumes without the need for complex near-field microscopes. Here, we demonstrate an all-optical probing technique based on plasmonic smart dust for monitoring local chemical reactions in real time. The silica shell-isolated gold nanoparticles that form the smart dust can work as strong light concentrators and optically report subtle environmental changes at their pinning sites on the probed surface during reaction processes. As a model system, we investigate the hydrogen dissociation and subsequent uptake trajectory in palladium with both "dust-on-film" and "film-on-dust" platforms. Using time-resolved single particle measurements, we demonstrate that our technique can in situ encode chemical reaction information as optical signals for a variety of surface morphologies. The presented technique offers a unique scheme for real-time, label-free, and high-resolution probing of local reaction kinetics in a plethora of important chemical reactions on surfaces, paving the way toward the development of inexpensive and high-output reaction sensors for real-world applications.

  16. Reaction Decoder Tool (RDT): extracting features from chemical reactions

    Rahman, Syed Asad; Torrance, Gilliean; Baldacci, Lorenzo; Martínez Cuesta, Sergio; Fenninger, Franz; Gopal, Nimish; Choudhary, Saket; May, John W.; Holliday, Gemma L.; Steinbeck, Christoph; Thornton, Janet M.


    Summary: Extracting chemical features like Atom–Atom Mapping (AAM), Bond Changes (BCs) and Reaction Centres from biochemical reactions helps us understand the chemical composition of enzymatic reactions. Reaction Decoder is a robust command line tool, which performs this task with high accuracy. It supports standard chemical input/output exchange formats i.e. RXN/SMILES, computes AAM, highlights BCs and creates images of the mapped reaction. This aids in the analysis of metabolic pathways and the ability to perform comparative studies of chemical reactions based on these features. Availability and implementation: This software is implemented in Java, supported on Windows, Linux and Mac OSX, and freely available at Contact: or PMID:27153692

  17. Reaction Decoder Tool (RDT): extracting features from chemical reactions.

    Rahman, Syed Asad; Torrance, Gilliean; Baldacci, Lorenzo; Martínez Cuesta, Sergio; Fenninger, Franz; Gopal, Nimish; Choudhary, Saket; May, John W; Holliday, Gemma L; Steinbeck, Christoph; Thornton, Janet M


    Extracting chemical features like Atom-Atom Mapping (AAM), Bond Changes (BCs) and Reaction Centres from biochemical reactions helps us understand the chemical composition of enzymatic reactions. Reaction Decoder is a robust command line tool, which performs this task with high accuracy. It supports standard chemical input/output exchange formats i.e. RXN/SMILES, computes AAM, highlights BCs and creates images of the mapped reaction. This aids in the analysis of metabolic pathways and the ability to perform comparative studies of chemical reactions based on these features. This software is implemented in Java, supported on Windows, Linux and Mac OSX, and freely available at : or © The Author 2016. Published by Oxford University Press.

  18. Recommendations for the generation, quantification, storage and handling of peptides used for mass spectrometry-based assays

    Hoofnagle, Andrew N.; Whiteaker, Jeffrey R.; Carr, Steven A.; Kuhn, Eric; Liu, Tao; Massoni, Sam A.; Thomas, Stefani N.; Townsend, Reid; Zimmerman, Lisa J.; Boja, Emily; Chen, Jing; Crimmins, Daniel L.; Davies, Sherri; Gao, Yuqian; Hiltke, Tara R.; Ketchum, Karen; Kinsinger, Christopher; Mesri, Mehdi; Meyer, Matthew R.; Qian, Weijun; Schoenherr, Regine M.; Scott, Mitchell; Shi, Tujin; Whiteley, Gordon; Wrobel, John; Wu, Chaochao; Ackermann, Bradley L.; Aebersold, Ruedi; Barnidge, David R.; Bunk, David M.; Clarke, Nigel; Fishman, Jordan B.; Grant, Russ P.; Kusebauch, Ulrike; Kushnir, Mark M.; Lowenthal, Mark S.; Moritz, Robert; Neubert, Hendrik; Patterson, Scott D.; Rockwood, Alan L.; Rogers, John; Singh, Ravinder J.; Van Eyk, Jennifer; Wong, Steven H.; Zhang, Shucha; Chan, Daniel W.; Chen, Xian; Ellis, Matthew J.; Liebler, Daniel; Rodland, Karin D.; Rodriguez, Henry; Smith, Richard D.; Zhang, Zhen; Zhang, Hui; Paulovich, Amanda G.


    The Clinical Proteomic Tumor Analysis Consortium (1) (CPTAC) of the National Cancer Institute (NCI) is a comprehensive and coordinated effort to accelerate the understanding of the molecular basis of cancer through the application of robust technologies and workflows for the quantitative measurements of proteins. The Assay Development Working Group of the CPTAC Program aims to foster broad uptake of targeted mass spectrometry-based assays employing isotopically labeled peptides for confident assignment and quantification, including multiple reaction monitoring (MRM; also referred to as Selected Reaction Monitoring), parallel reaction monitoring (PRM), and other targeted methods.

  19. Early Detection of Cancer by Affinity Mass Spectrometry-Set Aside funds — EDRN Public Portal

    A.   RATIONALE The recent introduction of multiple reaction monitoring capabilities offers unprecedented capability to the research arsenal available to protein based biomarker discovery. Specific to the discovery process this technology offers an ability to monitor specific protein changes in concentration and/or post-translational modification. The ability to accurately confirm specific biomarkers in a sensitive and reproducible manner is critical to the confirmation and pre-validation process. We are proposing two collaborative studies that promise to develop Multiple Reaction Monitoring (MRM) work flows for the biomarker scientific community and specifically for EDRN. B.   GOALS The overall goal for this proposal is the identification of protein biomarkers that can be associated with prostate cancer detection. The underlying goal is the application of a novel technological approach aided by MRM toward biomarker discovery. An additional goal will be the dissemination of knowledge gained from these studies EDRN wide.

  20. Effect of heavy atoms in bioluminescent reactions.

    Kirillova, Tamara N; Kudryasheva, Nadezhda S


    Bioluminescent reactions of luminous organisms are excellent models for studying the effects of heavy atoms on enzymatic processes. The effects of potassium halides with halide anions of different atomic weight were compared in bioluminescent reactions of the firefly (Luciola mingrelica), a marine coelenterate (Obelia longissima), and a marine bacterium (Photobacterium leiognathi). Two mechanisms of the effects of the halides were examined-the physicochemical effect of the external heavy atom, based on spin-orbit interactions in electron-excited structures, and the biochemical effect, i.e. interactions with the enzymes resulting in changes of enzymatic activity. The physicochemical effect was evaluated by using photoexcitation of model fluorescent compounds (flavin mononucleotide, firefly luciferin, and coelenteramide) of similar structure to the bioluminescence emitters. The bioluminescent and photoluminescent inhibition coefficients were calculated and compared for the luminous organisms to evaluate the relative contributions of the two mechanisms. The biochemical mechanism was found to be dominant. Hence, the bioluminescent reactions can be used as assays to monitor enzyme inhibition, in metabolic processes, by Br or I-containing compounds.

  1. The Glaser–Hay reaction

    Vilhelmsen, Mie Højer; Jensen, Jonas; Tortzen, Christian


    . This unfavorable change in reaction profile could be avoided by adding molecular sieves to the reaction mixture, thereby removing the water that is accumulated from the air and produced in the reaction in which dioxygen acts as the oxidizing agent. Not unexpectedly, the stirring rate, and hence uptake of air (O2...... on the scope of this reaction by using both 13C NMR and UV/Vis spectroscopic methods. The former method was used to study the kinetics of the coupling of aryl-substituted alkynes as the aryl carbon resonances of the reactants and products have similar NOEs and relaxation times. The reaction was found...

  2. The foreign body reaction to a biodegradable biomaterial differs between rats and mice

    Khouw, IMSL; van Wachem, PB; Molema, G; Plantinga, JA; de Leij, LFMH; van Luyn, MJA


    Before a biomaterial can be applied in the clinic, biocompatibility must be tested in in vivo models, by monitoring the foreign body reaction. In this study, we compared the foreign body reaction (EBR) to the biodegradable biomaterial hexamethylenediisocyanate crosslinked dermal sheep collagen (HDSC

  3. One-pot conversion reactions of glycosyl boranophosphates into glycosyl phosphate derivatives via acyl phosphite intermediates.

    Sato, Kazuki; Wada, Takeshi


    A one-pot synthesis of glycosyl phosphates and their P-modified analogs from glycosyl boranophosphates under mild basic conditions has been conducted. (31)P NMR monitoring of the reaction mixture revealed that the key intermediates of these reactions were acyl phosphites, which could not be formed from the corresponding H-phosphonate diesters.

  4. A review on mass spectrometry-based quantitative proteomics: Targeted and data independent acquisition.

    Vidova, Veronika; Spacil, Zdenek


    Mass spectrometry (MS) based proteomics have achieved a near-complete proteome coverage in humans and in several other organisms, producing a wealth of information stored in databases and bioinformatics resources. Recent implementation of selected/multiple reaction monitoring (SRM/MRM) technology in targeted proteomics introduced the possibility of quantitatively follow-up specific protein targets in a hypothesis-driven experiment. In contrast to immunoaffinity-based workflows typically used in biological and clinical research for protein quantification, SRM/MRM is characterized by high selectivity, large capacity for multiplexing (approx. 200 proteins per analysis) and rapid, cost-effective transition from assay development to deployment. The concept of SRM/MRM utilizes triple quadrupole (QqQ) mass analyzer to provide inherent reproducibility, unparalleled sensitivity and selectivity to efficiently differentiate isoforms, post-translational modifications and mutated forms of proteins. SRM-like targeted acquisitions such as parallel reaction monitoring (PRM) are pioneered on high resolution/accurate mass (HR/AM) platforms based on the quadrupole-orbitrap (Q-orbitrap) mass spectrometer. The expansion of HR/AM also caused development in data independent acquisition (DIA). This review presents a step-by-step tutorial on development of SRM/MRM protein assay intended for researchers without prior experience in proteomics. We discus practical aspects of SRM-based quantitative proteomics workflow, summarize milestones in basic biological and medical research as well as recent trends and emerging techniques. Copyright © 2017 Elsevier B.V. All rights reserved.

  5. Nuclear reactions an introduction

    Paetz gen. Schieck, Hans


    Nuclei and nuclear reactions offer a unique setting for investigating three (and in some cases even all four) of the fundamental forces in nature. Nuclei have been shown – mainly by performing scattering experiments with electrons, muons, and neutrinos – to be extended objects with complex internal structures: constituent quarks; gluons, whose exchange binds the quarks together; sea-quarks, the ubiquitous virtual quark-antiquark pairs and, last but not least, clouds of virtual mesons, surrounding an inner nuclear region, their exchange being the source of the nucleon-nucleon interaction.   The interplay between the (mostly attractive) hadronic nucleon-nucleon interaction and the repulsive Coulomb force is responsible for the existence of nuclei; their degree of stability, expressed in the details and limits of the chart of nuclides; their rich structure and the variety of their interactions. Despite the impressive successes of the classical nuclear models and of ab-initio approaches, there is clearly no ...

  6. Laser induced nuclear reactions

    Ledingham, Ken; McCanny, Tom; Graham, Paul; Fang, Xiao; Singhal, Ravi; Magill, Joe; Creswell, Alan; Sanderson, David; Allott, Ric; Neely, David; Norreys, Peter; Santala, Marko; Zepf, Matthew; Watts, Ian; Clark, Eugene; Krushelnick, Karl; Tatarakis, Michael; Dangor, Bucker; Machecek, Antonin; Wark, Justin


    Dramatic improvements in laser technology since 1984 have revolutionised high power laser technology. Application of chirped-pulse amplification techniques has resulted in laser intensities in excess of 1019W/cm2. In the mid to late eighties, C. K. Rhodes and K. Boyer discussed the possibility of shining laser light of this intensity onto solid surfaces and to cause nuclear transitions. In particular, irradiation of a uranium target could induce electro- and photofission in the focal region of the laser. In this paper it is shown that μCi of 62Cu can be generated via the (γ,n) reaction by a laser with an intensity of about 1019Wcm-2.

  7. Eikonal reaction theory

    Yahiro, Masanobu; Minomo, Kosho


    We present an accurate method of treating the one-neutron removal reaction at intermediate incident energies induced by both nuclear and Coulomb interactions. In the method, the nuclear and Coulomb breakup processes are consistently treated by the method of continuum discretized coupled channels without making the adiabatic approximation to the Coulomb interaction, so that the removal cross section calculated never diverges. This method is applied to recently measured one-neutron removal cross section for $^{31}$Ne+$^{12}$C scattering at 230 MeV/nucleon and $^{31}$Ne+$^{208}$Pb scattering at 234 MeV/nucleon. The spectroscopic factor and the asymptotic normalization coefficient of the last neutron in $^{31}$Ne are evaluated.

  8. Hypersensitivity reaction with deferasirox

    Atul Sharma


    Full Text Available Thalassemias comprise a group of hereditary blood disorders. Thalassemia major presents with anemia within the first 2 years of life requiring frequent blood transfusions for sustaining life. Regular blood transfusions lead to iron overload-related complications. Prognosis of thalassemia has improved because of the availability of iron-chelating agents. Oral iron chelators are the mainstay of chelation therapy. Deferasirox is a new-generation oral iron chelator for once daily usage. We herein describe a patient of beta thalassemia major who developed an allergic manifestation in the form of erythematous pruritic skin rashes to the oral iron chelator deferasirox. This is a rare adverse reaction reported with deferasirox that led to a therapeutic dilemma in this particular case.

  9. Hypersensitivity reaction with deferasirox.

    Sharma, Atul; Arora, Ekta; Singh, Harmanjit


    Thalassemias comprise a group of hereditary blood disorders. Thalassemia major presents with anemia within the first 2 years of life requiring frequent blood transfusions for sustaining life. Regular blood transfusions lead to iron overload-related complications. Prognosis of thalassemia has improved because of the availability of iron-chelating agents. Oral iron chelators are the mainstay of chelation therapy. Deferasirox is a new-generation oral iron chelator for once daily usage. We herein describe a patient of beta thalassemia major who developed an allergic manifestation in the form of erythematous pruritic skin rashes to the oral iron chelator deferasirox. This is a rare adverse reaction reported with deferasirox that led to a therapeutic dilemma in this particular case.

  10. Nuclear reactions in astrophysics

    Arnould, M.; Rayet, M. (Universite Libre de Bruxelles (BE))


    At all times and at all astrophysical scales, nuclear reactions have played and continue to play a key role. This concerns the energetics as well as the production of nuclides (nucleosynthesis). After a brief review of the observed composition of various objects in the universe, and especially of the solar system, the basic ingredients that are required in order to build up models for the chemical evolution of galaxies are sketched. Special attention is paid to the evaluation of the stellar yields through an overview of the important burning episodes and nucleosynthetic processes that can develop in non-exploding or exploding stars. Emphasis is put on the remaining astrophysical and nuclear physics uncertainties that hamper a clear understanding of the observed characteristics, and especially compositions, of a large variety of astrophysical objects.

  11. Kinetics of Bio-Reactions


    his chapter predicts the specific rates of reaction by means of a mathematical expression, the kinetics of the reaction. This expression can be derived through a mechanistic interpretation of an enzymatically catalyzed reaction, but it is essentially of empirical nature for cell reactions....... The models can be used in mass balances for design of processes under process conditions not yet studied experimentally. The value of the predictive kinetic model depends on the quality of the experimental data on which the model is based, and well-founded kinetic models for enzyme reactions have...... a considerable predictive power. This is also true for cell reaction models, when the model is used in its proper context. The chapter first discusses the kinetics for enzymatically catalyzed reactions (“enzyme reactions”). The kinetics can be derived from a mechanistic model. Then, the chapter derives empirical...

  12. Polymerization reaction in restricted space of layered double hydroxides (LDHs)

    SI Lichun; WANG Ge; CAI Fuli; WANG Zhiqiang; DUAN Xue


    This paper reported the preparation of styrene sulfonate intercalated layered double hydroxides (LDHs) material, SS-LDHs by coprecipitation method, followed by in-situ polymerization of the monomers in the interlayer space of LDHs. The polymerization reaction was monitored by UV and NMR. It is confirmed that when the reaction occurred at 100℃ for 24 h, part of monomers did not react .When the reaction was carried out at 150℃, the polymeriza tion of the intercalated monomers is complete to afford the polymer intercalated product PSS-LDHs. During the polymerization process, the layered structure remains well. At thesame time the gallery height increases with the lengthening of reaction time. This is preliminarily because that the PSS becomes more swelling with the amount of water it absorbs due to its hygroscopicity property.

  13. Chemical research on red pigments after adverse reactions to tattoo.

    Tammaro, A; Toniolo, C; Giulianelli, V; Serafini, M; Persechino, S


    Currently, the incidence of tattooing is on the rise compared to the past, especially among adolescents, and it leads to the urgency of monitoring the security status of tattooing centers, as well as to inform people about the risks of tattoo practice. In our clinical experience, 20% of tattooed patients presented adverse reactions, like allergic contact dermatitis, psoriasis with Koebner's phenomena and granulomatous reactions, with the latter most prevalent and most often related to red pigment. Adverse reactions to tattoo pigments, especially the red one, are well known and described in literature. Great attention has to be focused on the pigments used, especially for the presence of new substances, often not well known. For this reason, we decided to perform a study on 12 samples of red tattoo ink, obtained by patients affected by different cutaneous reactions in the site of tattoo, to analyze their chemical composition.

  14. Sky monitoring with LOBSTER

    Hudec, R.; Tichy, V.


    The X--ray sky monitoring represents valuable energy spectral extension to optical sky monitoring. Lobster--Eye all--sky monitors are able to provide relatively high sensitivity and good time resolution in the soft X--ray energy range up to 10 keV. The fine time resolution can be used to alert optical robotic telescopes for follow--up and multispectral analyzes in the visible light.

  15. Loads Monitoring and Hums


    Strain Measurement Fibre Optic Strain Temperature Pressure Crack Gage Crack Growth Accelerometer C.G. or Local Acceleration, Vibration, Buffet Pressure...Fig. 3.3-3 Zone 4 sensor location and results 1-15 A different method of monitoring structural health is shown in Fig. 3.3-4, a fibre optic array...Computer System Fig. 3.3-4 Fibre Optic monitoring array embedded in structure The two major tasks of structural health monitoring: Identification of

  16. Monitoring of radiation exposure



    The guide specifies the requirements for the monitoring of radiation exposure in instances where radiation is used. In addition to workers, the guide covers students, apprentices and visitors. The guide shall also apply to exposure from natural radiation. However, the monitoring of radiation exposure in nuclear power plants is dealt with in YVL Guide 7.10 and 7.11. The guide defines the concepts relevant to the monitoring of radiation exposure and provides guidelines for determining the necessity of monitoring and subsequently arranging such in different operations. In addition, the guide specifies the criteria for the approval and regulatory control of the dosimetric service.

  17. Monitoring of radiation exposure



    The guide specifies the requirements for the monitoring of radiation exposure in instances where radiation is used. In addition to workers, the guide covers students, apprentices and visitors. The guide shall also apply to exposure from natural radiation. However, the monitoring of radiation exposure in nuclear power plants is dealt with in YVL Guide 7.10 and 7.11. The guide defines the concepts relevant to the monitoring of radiation exposure and provides guidelines for determining the necessity of monitoring and subsequently arranging such in different operations. In addition, the guide specifies the criteria for the approval and regulatory control of the dosimetric service.

  18. Environmental monitoring plan

    Holland, R.C.


    This Environmental Monitoring Plan was written to fulfill the requirements of Department of Energy (DOE) Order 5400.1 and DOE Environmental Regulatory Guide DOE/EH 0173T. This Plan documents the background, organizational structure, and methods used for effluent monitoring and environmental surveillance at Sandia National Laboratories/California. The design, rationale, and historical results of the environmental monitoring system are discussed in detail. Throughout the Plan, recommendations for improvements to the monitoring system are made. 52 refs., 10 figs., 12 tabs.

  19. Remote Maintenance Monitoring System -

    Department of Transportation — The Remote Maintenance and Monitoring System (RMMS) is a collection of subsystems that includes telecommunication components, hardware, and software, which serve to...

  20. Aerospace Systems Monitor Project

    National Aeronautics and Space Administration — Proposal Title: Aerospace Systems Monitor PHASE 1 Technical Abstract: This Phase II STTR project will continue development and commercialization of the Aerospace...

  1. Network Monitoring with Nagios

    Dondich, Taylor


    Network monitoring can be a complex task to implement and maintain in your IT infrastructure. Nagios, an open-source host, service and network monitoring program can help you streamline your network monitoring tasks and reduce the cost of operation.With this shortcut guide, we'll go over how Nagios fits in the overall network monitoring puzzle. We'll also cover installation and basic usage. Finally, we'll show you how to extend Nagios with other tools to extend functionality.

  2. Detection of buffalo mozzarella adulteration by an ultra-high performance liquid chromatography tandem mass spectrometry methodology.

    Russo, Rosita; Severino, Valeria; Mendez, Alberto; Lliberia, Josep; Parente, Augusto; Chambery, Angela


    Over the past years, LC-MS-based approaches have gained a growing interest in food analysis by using different platforms and methodologies. In particular, enhanced selectivity and sensitivity of multiple reaction monitoring (MRM) scan function offer powerful capabilities in detecting and quantifying specific analytes within complex mixtures such as food matrices. The MRM approach, traditionally applied in biomedical research, is particularly suitable for the detection of food adulteration and for the verification of authenticity to assure food safety and quality, both recognized as top priorities by the European Union Commission. Increasingly stringent legislation ensure products safety along every step 'from farm to fork', especially for traditional foods designed with the Protected Designation of Origin certification. Therefore, there is a growing demand of new methodologies for defining food authenticity in order to preserve their unique traits against frauds. In this work, an ultra performance liquid chromatopgraphy-electrospray ionization-tandem mass spectrometry (MS/MS) methodology based on MRM has been developed for the sensitive and selective detection of buffalo mozzarella adulteration. The targeted quantitative analysis was performed by monitoring specific transitions of the phosphorylated β-casein f33-48 peptide, identified as a novel species-specific proteotypic marker. The high sensitivity of MRM-based MS and the wide dynamic range of triple quadrupole spectrometers have proved to be a valuable tool for the analysis of food matrices such as dairy products, thus offering new opportunities for monitoring food quality and adulterations. Copyright © 2012 John Wiley & Sons, Ltd.


    Bernard, F; Milcent, H; Petrova, L B; Varlea, F


    The Industrial Controls and Engineering (EN-ICE) group [1] of the Engineering Department at CERN has produced, and is responsible for the operation of around 60 applications, which control critical processes in the domains of cryogenics, quench protection systems, power interlocks for the Large Hadron Collider and other sub-systems of the accelerator complex. These applications require 24/7 operation and a quick reaction to problems. For this reason the EN-ICE group is presently developing the Monitoring Operation of cOntrols Networks (MOON) tool to detect, anticipate and inform of possible anomalies in the integrity of the applications. The tool builds on top of Simatic WinCC Open Architecture (WinCC OA) [2] SCADA and makes usage of the Joint COntrols Project (JCOP) [3] and the UNified INdustrial COntrol System (UNICOS) [4] Frameworks developed at CERN. The tool provides centralized monitoring and software management of the different elements integrating the control systems like Windows and Linux servers, PL...

  4. Synchronous monitoring of muscle dynamics and electromyogram

    Zakir Hossain, M.; Grill, Wolfgang


    A non-intrusive novel detection scheme has been implemented to detect the lateral muscle extension, force of the skeletal muscle and the motor action potential (EMG) synchronously. This allows the comparison of muscle dynamics and EMG signals as a basis for modeling and further studies to determine which architectural parameters are most sensitive to changes in muscle activity. For this purpose the transmission time for ultrasonic chirp signal in the frequency range of 100 kHz to 2.5 MHz passing through the muscle under observation and respective motor action potentials are recorded synchronously to monitor and quantify biomechanical parameters related to muscle performance. Additionally an ultrasonic force sensor has been employed for monitoring. Ultrasonic traducers are placed on the skin to monitor muscle expansion. Surface electrodes are placed suitably to pick up the potential for activation of the monitored muscle. Isometric contraction of the monitored muscle is ensured by restricting the joint motion with the ultrasonic force sensor. Synchronous monitoring was initiated by a software activated audio beep starting at zero time of the subsequent data acquisition interval. Computer controlled electronics are used to generate and detect the ultrasonic signals and monitor the EMG signals. Custom developed software and data analysis is employed to analyze and quantify the monitored data. Reaction time, nerve conduction speed, latent period between the on-set of EMG signals and muscle response, degree of muscle activation and muscle fatigue development, rate of energy expenditure and motor neuron recruitment rate in isometric contraction, and other relevant parameters relating to muscle performance have been quantified with high spatial and temporal resolution.

  5. Click chemistry based biomolecular conjugation monitoring using surface-enhanced Raman spectroscopy mapping

    Palla, Mirko; Kumar, Shiv; Li, Zengmin


    We describe here a novel surface-enhanced Raman spectroscopy (SERS) based technique for monitoring the conjugation of small molecules by the well-known click reaction between an alkyne and azido moiety on the partner molecules. The monitoring principle is based on the loss of the characteristic...... alkyne/azide Raman signal with triazole formation in the reaction as a function of time. Since these universal Raman reporter groups are specific for click reactions, this method may facilitate a broad range of applications for monitoring the conjugation efficiency of molecules in diverse areas...

  6. Resonance Reaction in Diffusion-Influenced Bimolecular Reactions

    Kolb, Jakob J; Dzubiella, Joachim


    We investigate the influence of a stochastically fluctuating step-barrier potential on bimolecular reaction rates by exact analytical theory and stochastic simulations. We demonstrate that the system exhibits a new resonant reaction behavior with rate enhancement if an appropriately defined fluctuation decay length is of the order of the system size. Importantly, we find that in the proximity of resonance the standard reciprocal additivity law for diffusion and surface reaction rates is violated due to the dynamical coupling of multiple kinetic processes. Together, these findings may have important repercussions on the correct interpretation of various kinetic reaction problems in complex systems, as, e.g., in biomolecular association or catalysis.

  7. Photoinitiated reactions in weakly bonded complexes

    Wittig, C.


    This paper discusses photoinitiated reactions in weakly bonded binary complexes in which the constituents are only mildly perturbed by the intermolecular bond. Such complexes, with their large zero point excursions, set the stage for events that occur following electronic excitation of one of the constituents. This can take several forms, but in all cases, entrance channel specificity is imposed by the character of the complex as well as the nature of the photoinitiation process. This has enabled us to examine aspects of bimolecular processes: steric effects, chemical branching ratios, and inelastic scattering. Furthermore, monitoring reactions directly in the time domain can reveal mechanisms that cannot be inferred from measurements of nascent product excitations. Consequently, we examined several systems that had been studied previously by our group with product state resolution. With CO{sub 2}/HI, in which reaction occurs via a HOCO intermediate, the rates agree with RRKM predictions. With N{sub 2}O/HI, the gas phase single collision reaction yielding OH + N{sub 2} has been shown to proceed mainly via an HNNO intermediate that undergoes a 1,3-hydrogen shift to the OH + N{sub 2} channel. With complexes, ab initio calculations and high resolution spectroscopic studies of analogous systems suggest that the hydrogen, while highly delocalized, prefers the oxygen to the nitrogen. We observe that OH is produced with a fast risetime (< 250 fs) which can be attributed to either direct oxygen-side attack or rapid HNNO decomposition and/or a termolecular contribution involving the nearby iodine.

  8. Hemolytic Transfusion Reactions

    Fatih Mehmet Azık


    Full Text Available The prevalence of fatal hemolytic transfusion reactions (HTRs is approximately 1:200000 per unit. Acute HTRs occur during or within 24 h after administration of a blood product. Transfusion of incompatible red blood cells (RBCs, and, more rarely, of a large volume of incompatible plasma usually are the causative agents. Delayed HTRs are caused by a secondary immune response to an antigen on the donor’s RBCs. Different mechanisms lead to intra- and extravascular hemolysis, such as complete complement activation, phagocytosis of RBCs covered with C3b by macrophages after incomplete complement activation, or destruction of RBCs covered only with IgG by direct cell to cell contact with K cells. The clinical consequences of HTRs are triggered via several pathophysiological pathways. Formation of anaphylatoxins, release of cytokines causing a systemic inflammatory response syndrome, activation of the kinin system, the intrinsic clotting cascade and fibrinolysis result in hypotension, disseminated intravascular coagulation, diffuse bleeding, and disruption of microcirculation leading to renal failure and shock. In this review, the symptoms of HTR are introduced, laboratory investigations and treatment are described, and some recommendations for prevention are given. (Journal of Current Pediatrics 2011; 9: 127-32

  9. NIF Gamma Reaction History

    Herrmann, H. W.; Kim, Y.; Young, C. S.; Mack, J. M.; McEvoy, A. M.; Hoffman, N. M.; Wilson, D. C.; Langenbrunner, J. R.; Evans, S.; Batha, S. H.; Stoeffl, W.; Lee, A.; Horsfield, C. J.; Rubery, M.; Miller, E. K.; Malone, R. M.; Kaufman, M. I.


    The primary objective of the NIF Gamma Reaction History (GRH) diagnostics is to provide bang time and burn width information based upon measurement of fusion gamma-rays. This is accomplished with energy-thresholded Gas Cherenkov detectors that convert MeV gamma-rays into UV/visible photons for high-bandwidth optical detection. In addition, the GRH detectors can perform γ-ray spectroscopy to explore other nuclear processes from which additional significant implosion parameters may be inferred (e.g., plastic ablator areal density). Implementation is occurring in 2 phases: 1) four PMT-based channels mounted to the outside of the NIF target chamber at ˜6 m from TCC (GRH-6m) for the 3e13-3e16 DT neutron yield range expected during the early ignition-tuning campaigns; and 2) several channels located just inside the target bay shield wall at ˜15 m from TCC (GRH-15m) with optical paths leading through the wall into well-shielded streak cameras and PMTs for the 1e16-1e20 yield range expected during the DT ignition campaign. This suite of diagnostics will allow exploration of interesting γ-ray physics well beyond the ignition campaign. Recent data from OMEGA and NIF will be shown.

  10. Biological water quality monitoring using chemiluminescent and bioluminescent techniques

    Thomas, R. R.


    Automated chemiluminescence and bioluminescence sensors were developed for the continuous monitoring of microbial levels in water supplies. The optimal chemical procedures were determined for the chemiluminescence system to achieve maximum sensitivity. By using hydrogen peroxide, reaction rate differentiation, ethylene diamine tetraacetic acid (EDTA), and carbon monoxide pretreatments, factors which cause interference were eliminated and specificity of the reaction for living and dead bacteria was greatly increased. By employing existing technology with some modifications, a sensitive and specific bioluminescent system was developed.

  11. Targeted MS Assay Predicting Tamoxifen Resistance in Estrogen-Receptor-Positive Breast Cancer Tissues and Sera.

    De Marchi, Tommaso; Kuhn, Erik; Dekker, Lennard J; Stingl, Christoph; Braakman, Rene B H; Opdam, Mark; Linn, Sabine C; Sweep, Fred C G J; Span, Paul N; Luider, Theo M; Foekens, John A; Martens, John W M; Carr, Steven A; Umar, Arzu


    We recently reported on the development of a 4-protein-based classifier (PDCD4, CGN, G3BP2, and OCIAD1) capable of predicting outcome to tamoxifen treatment in recurrent, estrogen-receptor-positive breast cancer based on high-resolution MS data. A precise and high-throughput assay to measure these proteins in a multiplexed, targeted fashion would be favorable to measure large numbers of patient samples to move these findings toward a clinical setting. By coupling immunoprecipitation to multiple reaction monitoring (MRM) MS and stable isotope dilution, we developed a high-precision assay to measure the 4-protein signature in 38 primary breast cancer whole tissue lysates (WTLs). Furthermore, we evaluated the presence and patient stratification capabilities of our signature in an independent set of 24 matched (pre- and post-therapy) sera. We compared the performance of immuno-MRM (iMRM) with direct MRM in the absence of fractionation and shotgun proteomics in combination with label-free quantification (LFQ) on both WTL and laser capture microdissected (LCM) tissues. Measurement of the 4-proteins by iMRM showed not only higher accuracy in measuring proteotypic peptides (Spearman r: 0.74 to 0.93) when compared with MRM (Spearman r: 0.0 to 0.76) but also significantly discriminated patient groups based on treatment outcome (hazard ratio [HR]: 10.96; 95% confidence interval [CI]: 4.33 to 27.76; Log-rank P < 0.001) when compared with LCM (HR: 2.85; 95% CI: 1.24 to 6.54; Log-rank P = 0.013) and WTL (HR: 1.16; 95% CI: 0.57 to 2.33; Log-rank P = 0.680) LFQ-based predictors. Serum sample analysis by iMRM confirmed the detection of the four proteins in these samples. We hereby report that iMRM outperformed regular MRM, confirmed our previous high-resolution MS results in tumor tissues, and has shown that the 4-protein signature is measurable in serum samples.

  12. The Progression of Sequential Reactions

    Jack McGeachy


    Full Text Available Sequential reactions consist of linked reactions in which the product of the first reaction becomes the substrate of a second reaction. Sequential reactions occur in industrially important processes, such as the chlorination of methane. A generalized series of three sequential reactions was analyzed in order to determine the times at which each chemical species reaches its maximum. To determine the concentration of each species as a function of time, the differential rate laws for each species were solved. The solution of each gave the concentration curve of the chemical species. The concentration curves of species A1 and A2 possessed discreet maxima, which were determined through slope-analysis. The concentration curve of the final product, A3, did not possess a discreet maximum, but rather approached a finite limit.

  13. Microwave-Accelerated Organic Reactions

    LU; TaJung


    The use of microwave technology in accelerating organic reactions has received intense attention leading to immense growth recently. Accordingly, we have been interested in improving the efficacy of organic processes by microwave irradiation. Here we report our results on the microwave assisted 1,3-dipolar cycloaddition reaction of nitrile oxides with allylic alcohols, the cleavage reaction of 1,3-diketones under alkaline conditions, and the formation of carbamates from isocyanates with alcohols. The reactions carried out under microwave irradiation, in general, required considerably less reaction time and afforded the desired products in higher yields than those under classical conditions. In all the cases we have studied, the procedures are simplified, the purity of the products are higher, and the cost of reaction is greatly reduced employing microwave.  ……

  14. Microwave-Accelerated Organic Reactions

    LU TaJung


    @@ The use of microwave technology in accelerating organic reactions has received intense attention leading to immense growth recently. Accordingly, we have been interested in improving the efficacy of organic processes by microwave irradiation. Here we report our results on the microwave assisted 1,3-dipolar cycloaddition reaction of nitrile oxides with allylic alcohols, the cleavage reaction of 1,3-diketones under alkaline conditions, and the formation of carbamates from isocyanates with alcohols. The reactions carried out under microwave irradiation, in general, required considerably less reaction time and afforded the desired products in higher yields than those under classical conditions. In all the cases we have studied, the procedures are simplified, the purity of the products are higher, and the cost of reaction is greatly reduced employing microwave.

  15. Water Quality Monitoring Manual.

    Mason, Fred J.; Houdart, Joseph F.

    This manual is designed for students involved in environmental education programs dealing with water pollution problems. By establishing a network of Environmental Monitoring Stations within the educational system, four steps toward the prevention, control, and abatement of water pollution are proposed. (1) Train students to recognize, monitor,…

  16. Improved Marine Waters Monitoring

    Palazov, Atanas; Yakushev, Evgeniy; Milkova, Tanya; Slabakova, Violeta; Hristova, Ognyana


    IMAMO - Improved Marine Waters Monitoring is a project under the Programme BG02: Improved monitoring of marine waters, managed by Bulgarian Ministry of environment and waters and co-financed by the Financial Mechanism of the European Economic Area (EEA FM) 2009 - 2014. Project Beneficiary is the Institute of oceanology - Bulgarian Academy of Sciences with two partners: Norwegian Institute for Water Research and Bulgarian Black Sea Basin Directorate. The Project aims to improve the monitoring capacity and expertise of the organizations responsible for marine waters monitoring in Bulgaria to meet the requirements of EU and national legislation. The main outcomes are to fill the gaps in information from the Initial assessment of the marine environment and to collect data to assess the current ecological status of marine waters including information as a base for revision of ecological targets established by the monitoring programme prepared in 2014 under Art. 11 of MSFD. Project activities are targeted to ensure data for Descriptors 5, 8 and 9. IMAMO aims to increase the institutional capacity of the Bulgarian partners related to the monitoring and assessment of the Black Sea environment. The main outputs are: establishment of real time monitoring and set up of accredited laboratory facilities for marine waters and sediments chemical analysis to ensure the ability of Bulgarian partners to monitor progress of subsequent measures undertaken.

  17. Strategic Tutor Monitoring.

    Chee-kwong, Kenneth Chao


    Discusses effective tutor monitoring strategies based on experiences at the Open Learning Institute of Hong Kong. Highlights include key performance and strategic control points; situational factors, including tutor expectations and relevant culture; Theory X versus Theory Y leadership theories; and monitoring relationships with tutors. (LRW)

  18. Strategic Tutor Monitoring.

    Chee-kwong, Kenneth Chao


    Discusses effective tutor monitoring strategies based on experiences at the Open Learning Institute of Hong Kong. Highlights include key performance and strategic control points; situational factors, including tutor expectations and relevant culture; Theory X versus Theory Y leadership theories; and monitoring relationships with tutors. (LRW)

  19. Mariene monitoring & Natura 2000

    Paijmans, A.J.; Asjes, J.


    IMARES heeft in opdracht van het ministerie van EL&I een rapport opgesteld over de eisen die de Habitatrichtlijn en de Vogelrichtlijn stellen ten aanzien van de monitoring in de Nederlandse zoute wateren. Vervolgens is geanalyseerd waar de huidige monitoring die wordt uitgevoerd voldoet aan deze

  20. Global nuclear material monitoring

    Howell, J.A.; Monlove, H.O.; Goulding, C.A.; Martinez, B.J.; Coulter, C.A.


    This is the final report of a one-year Laboratory-Directed Research and Development (LDRD) project at the Los Alamos National Laboratory (LANL). This project provided a detailed systems design for advanced integrated facility monitoring and identified the components and enabling technologies required to facilitate the development of the monitoring system of the future.

  1. Facility effluent monitoring

    Gleckler, B.P.


    This section of the 1994 Hanford Site Environmental Report summarizes the facility effluent monitoring programs and provides an evaluation of effluent monitoring data. These evaluations are useful in assessing the effectiveness of effluent treatment and control systems, as well as management practices.

  2. Monitoring Evolution at CERN

    Andrade, P; Murphy, S; Pigueiras, L; Santos, M


    Over the past two years, the operation of the CERN Data Centres went through significant changes with the introduction of new mechanisms for hardware procurement, new services for cloud provisioning and configuration management, among other improvements. These changes resulted in an increase of resources being operated in a more dynamic environment. Today, the CERN Data Centres provide over 11000 multi-core processor servers, 130 PB disk servers, 100 PB tape robots, and 150 high performance tape drives. To cope with these developments, an evolution of the data centre monitoring tools was also required. This modernisation was based on a number of guiding rules: sustain the increase of resources, adapt to the new dynamic nature of the data centres, make monitoring data easier to share, give more flexibility to Service Managers on how they publish and consume monitoring metrics and logs, establish a common repository of monitoring data, optimise the handling of monitoring notifications, and replace the previous ...

  3. Job Oriented Monitoring Clusters

    Vijayalaxmi Cigala,


    Full Text Available There has been a lot of development in the field of clusters and grids. Recently, the use of clusters has been on rise in every possible field. This paper proposes a system that monitors jobs onlarge computational clusters. Monitoring jobs is essential to understand how jobs are being executed. This helps us in understanding the complete life cycle of the jobs being executed on large clusters. Also, this paper describes how the information obtained by monitoring the jobs would help in increasing the overall throughput of clusters. Heuristics help in efficient job distribution among the computational nodes, thereby accomplishing fair job distribution policy. The proposed system would be capable of loadbalancing among the computational nodes, detecting failures, taking corrective actions after failure detection, job monitoring, system resource monitoring, etc.

  4. Monitoring for conservation

    Nichols, J.D.; Williams, B.K.


    Human-mediated environmental changes have resulted in appropriate concern for the conservation of ecological systems and have led to the development of many ecological monitoring programs worldwide. Many programs that are identified with the purpose of `surveillance? represent an inefficient use of conservation funds and effort. Here, we revisit the 1964 paper by Platt and argue that his recommendations about the conduct of science are equally relevant to the conduct of ecological monitoring programs. In particular, we argue that monitoring should not be viewed as a stand-alone activity, but instead as a component of a larger process of either conservation-oriented science or management. Corresponding changes in monitoring focus and design would lead to substantial increases in the efficiency and usefulness of monitoring results in conservation.

  5. Monitoring Cray Cooling Systems

    Maxwell, Don E [ORNL; Ezell, Matthew A [ORNL; Becklehimer, Jeff [Cray, Inc.; Donovan, Matthew J [ORNL; Layton, Christopher C [ORNL


    While sites generally have systems in place to monitor the health of Cray computers themselves, often the cooling systems are ignored until a computer failure requires investigation into the source of the failure. The Liebert XDP units used to cool the Cray XE/XK models as well as the Cray proprietary cooling system used for the Cray XC30 models provide data useful for health monitoring. Unfortunately, this valuable information is often available only to custom solutions not accessible by a center-wide monitoring system or is simply ignored entirely. In this paper, methods and tools used to harvest the monitoring data available are discussed, and the implementation needed to integrate the data into a center-wide monitoring system at the Oak Ridge National Laboratory is provided.

  6. Speeding chemical reactions by focusing

    Lacasta, A M; Sancho, J M; Lindenberg, K


    We present numerical results for a chemical reaction of colloidal particles which are transported by a laminar fluid and are focused by periodic obstacles in such a way that the two components are well mixed and consequently the chemical reaction is speeded up. The roles of the various system parameters (diffusion coefficients, reaction rate, obstacles sizes) are studied. We show that focusing speeds up the reaction from the diffusion limited rate (t to the power -1/2) to very close to the perfect mixing rate, (t to the power -1).

  7. Radiation reaction in fusion plasmas.

    Hazeltine, R D; Mahajan, S M


    The effects of a radiation reaction on thermal electrons in a magnetically confined plasma, with parameters typical of planned burning plasma experiments, are studied. A fully relativistic kinetic equation that includes the radiation reaction is derived. The associated rate of phase-space contraction is computed and the relative importance of the radiation reaction in phase space is estimated. A consideration of the moments of the radiation reaction force show that its effects are typically small in reactor-grade confined plasmas, but not necessarily insignificant.

  8. [Situational reactions in suicidologic practice].

    Ambrumova, A G; Vrono, E M


    The paper is devoted to the description of suicidal manifestations in mentally normal adolescents among typical behavioural disorders characteristic of situational reactions of this age. Three types of suicido-dangerous situational responses of adolescents were specified with regard to their age and auto-and heteaggressiveness ratio: reaction of deprivation, explosive reaction and reaction of auto-elimination. Suicidogenic conflicts were analyzed and spheres of age-specific suicidal conflicts were defined. It is advisable that outpatient management of mentally normal adolescents with a history of a suicidal attempt be conducted in a special room of presentive suicidological service.

  9. Kinematically complete chemical reaction dynamics

    Trippel, S.; Stei, M.; Otto, R.; Hlavenka, P.; Mikosch, J.; Eichhorn, C.; Lourderaj, U.; Zhang, J. X.; Hase, W. L.; Weidemüller, M.; Wester, R.


    Kinematically complete studies of molecular reactions offer an unprecedented level of insight into the dynamics and the different mechanisms by which chemical reactions occur. We have developed a scheme to study ion-molecule reactions by velocity map imaging at very low collision energies. Results for the elementary nucleophilic substitution (SN2) reaction Cl- + CH3I → ClCH3 + I- are presented and compared to high-level direct dynamics trajectory calculations. Furthermore, an improved design of the crossed-beam imaging spectrometer with full three-dimensional measurement capabilities is discussed and characterization measurements using photoionization of NH3 and photodissociation of CH3I are presented.

  10. Pathophysiology of hemolytic transfusion reactions.

    Davenport, Robertson D


    Hemolytic transfusion reactions (HTR) are systemic reactions provoked by immunologic red blood cell (RBC) incompatibility. Clinical and experimental observations of such reactions indicate that they proceed through phases of humoral immune reaction, activation of phagocytes, productions of cytokine mediators, and wide-ranging cellular responses. HTR have many features in common with the systemic inflammatory response syndrome (SIRS). Knowledge of the pathophysiologic mechanisms in HTR suggest that newer biological agents that target complement intermediates or proinflammatory cytokines may be effective agents in the treatment of severe HTRs.

  11. Dynamic Reaction Figures: An Integrative Vehicle for Understanding Chemical Reactions

    Schultz, Emeric


    A highly flexible learning tool, referred to as a dynamic reaction figure, is described. Application of these figures can (i) yield the correct chemical equation by simply following a set of menu driven directions; (ii) present the underlying "mechanism" in chemical reactions; and (iii) help to solve quantitative problems in a number of different…

  12. Geoelectrical monitoring of bioremediation: the DNAPL problem

    Ntarlagiannis, D.; Slater, L. D.; Kulessa, B.; Kalin, R.


    Geo-electrical methods (e.g. resistivity, induced polarization and self potential) are increasingly being utilized as monitoring aids in remediation experiments. Recent field applications highlight the potential value of these methods in long-term monitoring, and current laboratory research is improving the quantitative interpretation of these geo-electrical signals. However, whereas this has proven true for the remediation of insoluble particles (e.g. heavy metals) and light non-aqueous phase liquids (LNAPLs), geoelectrical monitoring of dense non-aqueous phase liquid (DNAPL) has proven more challenging. Here we report the results of a column experiment aimed at monitoring bio-degradation of DNAPLs using geo-electrical and electrodic potential (based on reactions at the surface of electrodes) methods. We recorded strong electrodic potential signals concurrent with the degradation of the DNAPL as evident from geochemical monitoring (pH,Eh, total organic content, alkalinity, fluid conductivity, gas chromatography/and mass spectrometry). However, resistivity and induced polarization measurements were unresponsive to the degradation processes and apparently insensitive to microbial activity in this DNAPL contaminated system. Our results suggest that some of the characteristic biogeophysical signals associated with microbial growth detected in uncontaminated and LNAPL contaminated systems may not necessarily be observed during DNAPL biodegradation during the time-scale of typical laboratory and field geophysical experiments.

  13. Progress in microscopic direct reaction modeling of nucleon induced reactions

    Dupuis, M.; Bauge, E.; Hilaire, S.; Lechaftois, F.; Peru, S.; Pillet, N.; Robin, C. [CEA, DAM, DIF, Arpajon (France)


    A microscopic nuclear reaction model is applied to neutron elastic and direct inelastic scatterings, and pre-equilibrium reaction. The JLM folding model is used with nuclear structure information calculated within the quasi-particle random phase approximation implemented with the Gogny D1S interaction. The folding model for direct inelastic scattering is extended to include rearrangement corrections stemming from both isoscalar and isovector density variations occurring during a transition. The quality of the predicted (n,n), (n,n{sup '}), (n,xn) and (n,n{sup '}γ) cross sections, as well as the generality of the present microscopic approach, shows that it is a powerful tool that can help improving nuclear reactions data quality. Short- and long-term perspectives are drawn to extend the present approach to more systems, to include missing reactions mechanisms, and to consistently treat both structure and reaction problems. (orig.)

  14. Microscopic effective reaction theory for deuteron-induced reactions

    Neoh, Yuen Sim; Minomo, Kosho; Ogata, Kazuyuki


    The microscopic effective reaction theory is applied to deuteron-induced reactions. A reaction model-space characterized by a $p+n+{\\rm A}$ three-body model is adopted, where A is the target nucleus, and the nucleon-target potential is described by a microscopic folding model based on an effective nucleon-nucleon interaction in nuclear medium and a one-body nuclear density of A. The three-body scattering wave function in the model space is obtained with the continuum-discretized coupled-channels method (CDCC), and the eikonal reaction theory (ERT), an extension of CDCC, is applied to the calculation of neutron removal cross sections. Elastic scattering cross sections of deuteron on $^{58}$Ni and $^{208}$Pb target nuclei at several energies are compared with experimental data. The total reaction cross sections and the neutron removal cross sections at 56 MeV on 14 target nuclei are calculated and compared with experimental values.

  15. Microscopic effective reaction theory for deuteron-induced reactions

    Neoh, Yuen Sim; Yoshida, Kazuki; Minomo, Kosho; Ogata, Kazuyuki


    The microscopic effective reaction theory is applied to deuteron-induced reactions. A reaction model space characterized by a p +n +A three-body model is adopted, where A is the target nucleus, and the nucleon-target potential is described by a microscopic folding model based on an effective nucleon-nucleon interaction in nuclear medium and a one-body nuclear density of A . The three-body scattering wave function in the model space is obtained with the continuum-discretized coupled-channels (CDCC) method, and the eikonal reaction theory (ERT), an extension of CDCC, is applied to the calculation of neutron removal cross sections. Elastic scattering cross sections of deuteron on 58Ni and 208Pb target nuclei at several energies are compared with experimental data. The total reaction cross sections and the neutron removal cross sections at 56 MeV on 14 target nuclei are calculated and compared with experimental values.

  16. Dicarbonyl Intermediates in the Maillard Reaction



    A bstract : The complexity of the Maillard reaction arises partly from multiple fragmentation reactions of the sugar moiety, constituting branch points in the reaction progress and establishing many parallel reaction pathways...

  17. Safety system status monitoring

    Lewis, J.R.; Morgenstern, M.H.; Rideout, T.H.; Cowley, P.J.


    The Pacific Northwest Laboratory has studied the safety aspects of monitoring the preoperational status of safety systems in nuclear power plants. The goals of the study were to assess for the NRC the effectiveness of current monitoring systems and procedures, to develop near-term guidelines for reducing human errors associated with monitoring safety system status, and to recommend a regulatory position on this issue. A review of safety system status monitoring practices indicated that current systems and procedures do not adequately aid control room operators in monitoring safety system status. This is true even of some systems and procedures installed to meet existing regulatory guidelines (Regulatory Guide 1.47). In consequence, this report suggests acceptance criteria for meeting the functional requirements of an adequate system for monitoring safety system status. Also suggested are near-term guidelines that could reduce the likelihood of human errors in specific, high-priority status monitoring tasks. It is recommended that (1) Regulatory Guide 1.47 be revised to address these acceptance criteria, and (2) the revised Regulatory Guide 1.47 be applied to all plants, including those built since the issuance of the original Regulatory Guide.

  18. Monitoring that matters

    Johnson, Douglas H.; Gitzen, Robert A.; Millspaugh, Joshua J.; Cooper, Andrew B.; Licht, Daniel S.


    Monitoring is a critically important activity for assessing the status of a system, such as the health of an individual, the balance in one's checking account, profits and losses of a business, the economic activity of a nation, or the size of an animal population. Monitoring is especially vital for evaluating changes in the system associated with specific known impacts occurring to the system. It is also valuable for detecting unanticipated changes in the system and identifying plausible causes of such changes, all in time to take corrective action. Before proceeding, we should define "monitoring." One definition of "monitor" (Microsoft Corporation 2009) is "to check something at regular intervals in order to find out how it is progressing or developing." The key point here is "at regular intervals," suggesting a continuing process. Some definitions do not indicate the repetitive nature of monitoring and are basically synonymous with "observing." Most monitoring, in the strict sense of the word, is intended to persist for long periods of time, perhaps indefinitely or permanently. Similarly, Thompson et al. (1998: 3) referred to the "repeated assessment of status" of something, but noted that the term "monitor" is sometimes used for analogous activities such as collecting baseline information or evaluating projects for either implementation or effectiveness. For their purposes, they restricted the term to involve repeated measurements collected at a specified frequency of time units. Let us adopt that definition, recognizing that repeated measurements imply collecting comparable information on each occasion.

  19. Switchgear condition monitoring

    Budyn, M. [ABB Corporate Research, Krakow (Poland); Karandikar, H.M.; Urmson, M.G. [ABB Inc., Lake Mary, FL (United States)


    Electric utilities strive to keep switchgear in proper condition over their long life. Medium voltage switchgear are one of the key components in electrical power systems used to distribute electrical power, selectively isolate electrical loads and protect loads from cascading failure. They generally include a combination of electrical elements such as disconnectors, fuses, circuit breakers and distribution bus bars arranged in a lineup of frames. Since switchgear distributes electrical current, heat buildup becomes an important characteristic to monitor. The most significant amount of heat dissipation is on distribution elements like bus bars. Unexpected temperature rise at a particular location may indicate corrosion or a defect. If left uncorrected, this defect could result in catastrophic failure resulting in deactivated loads and potentially hazardous conditions to personnel. Currently, switchgear bus temperature monitoring is done periodically by manual inspections using IR cameras or by fibre-optic systems. Both methods have limitations, such as inaccurate and infrequent readouts, high implementation cost and limited monitoring area. This paper presented a modern approach for condition monitoring based on passive, SAW-based, wireless sensors, reducing installation costs and enhancing monitoring by allowing measurements in previously unreachable locations. A practical implementation of the wireless condition monitoring system was illustrated as a part of a general, built-in, switchgear diagnostics and maintenance system. The use of miniature SAW sensors proved effective in monitoring breaker connectors and non-invasive installation inside the switchgear. 8 refs., 5 figs.

  20. Space weather monitoring with neutron monitor measurements

    Steigies, Christian [Christian-Albrechts-Universitaet zu Kiel (Germany)


    Space Weather affects many areas of the modern society, advance knowledge about space weather events is important to protect personnel and infrastructure. Cosmic Rays (CR) measurements by ground-based Neutron Monitors are influenced by Coronal Mass Ejections (CME), the intensity of the ever present Cosmic Rays is reduced in a Forbush decrease (Fd). In the case of very energetic CMEs, the measured intensity can be significantly increased in a Ground Level Enhancement (GLE). By detecting the anisotropy of the CR environment, a CME can be detected hours before it arrives at Earth. During a GLE the high-energy particles from the Sun can be detected before the more abundant lower energy particles arrive at Earth, thus allowing to take protective measures. Since the beginning of the Neutron Monitor Database (NMDB) project, which has been started in 2008 with funding from the European Commission, real-time data from Neutron Monitors around the world has been made available through one web-portal. We have more than doubled the number of stations providing data since the start of the project to now over 30 stations. The effectiveness of the ALERT applications which are based on NMDB data has been shown by the recent GLE71. We present different applications through which the measurements and different data products are accessible.