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Sample records for mass spectrometry-based approaches

  1. [Advances in mass spectrometry-based approaches for neuropeptide analysis].

    Science.gov (United States)

    Ji, Qianyue; Ma, Min; Peng, Xin; Jia, Chenxi; Ji, Qianyue

    2017-07-25

    Neuropeptides are an important class of endogenous bioactive substances involved in the function of the nervous system, and connect the brain and other neural and peripheral organs. Mass spectrometry-based neuropeptidomics are designed to study neuropeptides in a large-scale manner and obtain important molecular information to further understand the mechanism of nervous system regulation and the pathogenesis of neurological diseases. This review summarizes the basic strategies for the study of neuropeptides using mass spectrometry, including sample preparation and processing, qualitative and quantitative methods, and mass spectrometry imagining.

  2. A hybrid approach to protein differential expression in mass spectrometry-based proteomics

    KAUST Repository

    Wang, X.; Anderson, G. A.; Smith, R. D.; Dabney, A. R.

    2012-01-01

    MOTIVATION: Quantitative mass spectrometry-based proteomics involves statistical inference on protein abundance, based on the intensities of each protein's associated spectral peaks. However, typical MS-based proteomics datasets have substantial

  3. A hybrid approach to protein differential expression in mass spectrometry-based proteomics

    KAUST Repository

    Wang, X.

    2012-04-19

    MOTIVATION: Quantitative mass spectrometry-based proteomics involves statistical inference on protein abundance, based on the intensities of each protein\\'s associated spectral peaks. However, typical MS-based proteomics datasets have substantial proportions of missing observations, due at least in part to censoring of low intensities. This complicates intensity-based differential expression analysis. RESULTS: We outline a statistical method for protein differential expression, based on a simple Binomial likelihood. By modeling peak intensities as binary, in terms of \\'presence/absence,\\' we enable the selection of proteins not typically amenable to quantitative analysis; e.g. \\'one-state\\' proteins that are present in one condition but absent in another. In addition, we present an analysis protocol that combines quantitative and presence/absence analysis of a given dataset in a principled way, resulting in a single list of selected proteins with a single-associated false discovery rate. AVAILABILITY: All R code available here: http://www.stat.tamu.edu/~adabney/share/xuan_code.zip.

  4. Determination of the binding sites for oxaliplatin on insulin using mass spectrometry-based approaches

    DEFF Research Database (Denmark)

    Møller, Charlotte; Sprenger, Richard R.; Stürup, Stefan

    2011-01-01

    Using insulin as a model protein for binding of oxaliplatin to proteins, various mass spectrometric approaches and techniques were compared. Several different platinum adducts were observed, e.g. addition of one or two diaminocyclohexane platinum(II) (Pt(dach)) molecules. By top-down analysis...... and fragmentation of the intact insulin-oxaliplatin adduct using nano-electrospray ionisation quadrupole time-of-flight mass spectrometry (nESI-Q-ToF-MS), the major binding site was assigned to histidine5 on the insulin B chain. In order to simplify the interpretation of the mass spectrum, the disulphide bridges...... were reduced. This led to the additional identification of cysteine6 on the A chain as a binding site along with histidine5 on the B chain. Digestion of insulin-oxaliplatin with endoproteinase Glu-C (GluC) followed by reduction led to the formation of five peptides with Pt(dach) attached...

  5. Multiplatform Mass Spectrometry-Based Approach Identifies Extracellular Glycolipids of the Yeast Rhodotorula babjevae UCDFST 04-877.

    Science.gov (United States)

    Cajka, Tomas; Garay, Luis A; Sitepu, Irnayuli R; Boundy-Mills, Kyria L; Fiehn, Oliver

    2016-10-28

    A multiplatform mass spectrometry-based approach was used for elucidating extracellular lipids with biosurfactant properties produced by the oleaginous yeast Rhodotorula babjevae UCDFST 04-877. This strain secreted 8.6 ± 0.1 g/L extracellular lipids when grown in a benchtop bioreactor fed with 100 g/L glucose in medium without addition of hydrophobic substrate, such as oleic acid. Untargeted reversed-phase liquid chromatography-quadrupole/time-of-flight mass spectrometry (QTOFMS) detected native glycolipid molecules with masses of 574-716 Da. After hydrolysis into the fatty acid and sugar components and hydrophilic interaction chromatography-QTOFMS analysis, the extracellular lipids were found to consist of hydroxy fatty acids and sugar alcohols. Derivatization and chiral separation gas chromatography-mass spectrometry (GC-MS) identified these components as d-arabitol, d-mannitol, (R)-3-hydroxymyristate, (R)-3-hydroxypalmitate, and (R)-3-hydroxystearate. In order to assemble these substructures back into intact glycolipids that were detected in the initial screen, potential structures were in-silico acetylated to match the observed molar masses and subsequently characterized by matching predicted and observed MS/MS fragmentation using the Mass Frontier software program. Eleven species of acetylated sugar alcohol esters of hydroxy fatty acids were characterized for this yeast strain.

  6. "Polymeromics": Mass spectrometry based strategies in polymer science toward complete sequencing approaches: a review.

    Science.gov (United States)

    Altuntaş, Esra; Schubert, Ulrich S

    2014-01-15

    Mass spectrometry (MS) is the most versatile and comprehensive method in "OMICS" sciences (i.e. in proteomics, genomics, metabolomics and lipidomics). The applications of MS and tandem MS (MS/MS or MS(n)) provide sequence information of the full complement of biological samples in order to understand the importance of the sequences on their precise and specific functions. Nowadays, the control of polymer sequences and their accurate characterization is one of the significant challenges of current polymer science. Therefore, a similar approach can be very beneficial for characterizing and understanding the complex structures of synthetic macromolecules. MS-based strategies allow a relatively precise examination of polymeric structures (e.g. their molar mass distributions, monomer units, side chain substituents, end-group functionalities, and copolymer compositions). Moreover, tandem MS offer accurate structural information from intricate macromolecular structures; however, it produces vast amount of data to interpret. In "OMICS" sciences, the software application to interpret the obtained data has developed satisfyingly (e.g. in proteomics), because it is not possible to handle the amount of data acquired via (tandem) MS studies on the biological samples manually. It can be expected that special software tools will improve the interpretation of (tandem) MS output from the investigations of synthetic polymers as well. Eventually, the MS/MS field will also open up for polymer scientists who are not MS-specialists. In this review, we dissect the overall framework of the MS and MS/MS analysis of synthetic polymers into its key components. We discuss the fundamentals of polymer analyses as well as recent advances in the areas of tandem mass spectrometry, software developments, and the overall future perspectives on the way to polymer sequencing, one of the last Holy Grail in polymer science. Copyright © 2013 Elsevier B.V. All rights reserved.

  7. Mass Spectrometry-based Approaches to Understand the Molecular Basis of Memory

    Directory of Open Access Journals (Sweden)

    Arthur Henriques Pontes

    2016-10-01

    Full Text Available The central nervous system is responsible for an array of cognitive functions such as memory, learning, language and attention. These processes tend to take place in distinct brain regions; yet, they need to be integrated to give rise to adaptive or meaningful behavior. Since cognitive processes result from underlying cellular and molecular changes, genomics and transcriptomics assays have been applied to human and animal models to understand such events. Nevertheless, genes and RNAs are not the end products of most biological functions. In order to gain further insights toward the understanding of brain processes, the field of proteomics has been of increasing importance in the past years. Advancements in liquid chromatography-tandem mass spectrometry (LC-MS/MS have enable the identification and quantification of thousand of proteins with high accuracy and sensitivity, fostering a revolution in the neurosciences. Herein, we review the molecular bases of explicit memory in the hippocampus. We outline the principles of mass spectrometry (MS-based proteomics, highlighting the use of this analytical tool to study memory formation. In addition, we discuss MS-based targeted approaches as the future of protein analysis.

  8. Optimization of information content in a mass spectrometry based flow-chemistry system by investigating different ionization approaches.

    Science.gov (United States)

    Martha, Cornelius T; Hoogendoorn, Jan-Carel; Irth, Hubertus; Niessen, Wilfried M A

    2011-05-15

    Current development in catalyst discovery includes combinatorial synthesis methods for the rapid generation of compound libraries combined with high-throughput performance-screening methods to determine the associated activities. Of these novel methodologies, mass spectrometry (MS) based flow chemistry methods are especially attractive due to the ability to combine sensitive detection of the formed reaction product with identification of introduced catalyst complexes. Recently, such a mass spectrometry based continuous-flow reaction detection system was utilized to screen silver-adducted ferrocenyl bidentate catalyst complexes for activity in a multicomponent synthesis of a substituted 2-imidazoline. Here, we determine the merits of different ionization approaches by studying the combination of sensitive detection of product formation in the continuous-flow system with the ability to simultaneous characterize the introduced [ferrocenyl bidentate+Ag](+) catalyst complexes. To this end, we study the ionization characteristics of electrospray ionization (ESI), atmospheric-pressure chemical ionization (APCI), no-discharge APCI, dual ESI/APCI, and dual APCI/no-discharge APCI. Finally, we investigated the application potential of the different ionization approaches by the investigation of ferrocenyl bidentate catalyst complex responses in different solvents. Copyright © 2011 Elsevier B.V. All rights reserved.

  9. A comparison of labeling and label-free mass spectrometry-based proteomics approaches.

    Science.gov (United States)

    Patel, Vibhuti J; Thalassinos, Konstantinos; Slade, Susan E; Connolly, Joanne B; Crombie, Andrew; Murrell, J Colin; Scrivens, James H

    2009-07-01

    The proteome of the recently discovered bacterium Methylocella silvestris has been characterized using three profiling and comparative proteomics approaches. The organism has been grown on two different substrates enabling variations in protein expression to be identified. The results obtained using the experimental approaches have been compared with respect to number of proteins identified, confidence in identification, sequence coverage and agreement of regulated proteins. The sample preparation, instrumental time and sample loading requirements of the differing experiments are compared and discussed. A preliminary screen of the protein regulation results for biological significance has also been performed.

  10. A Stable-Isotope Mass Spectrometry-Based Metabolic Footprinting Approach to Analyze Exudates from Phytoplankton

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    Mark R. Viant

    2013-10-01

    Full Text Available Phytoplankton exudates play an important role in pelagic ecology and biogeochemical cycles of elements. Exuded compounds fuel the microbial food web and often encompass bioactive secondary metabolites like sex pheromones, allelochemicals, antibiotics, or feeding attractants that mediate biological interactions. Despite this importance, little is known about the bioactive compounds present in phytoplankton exudates. We report a stable-isotope metabolic footprinting method to characterise exudates from aquatic autotrophs. Exudates from 13C-enriched alga were concentrated by solid phase extraction and analysed by high-resolution Fourier transform ion cyclotron resonance mass spectrometry. We used the harmful algal bloom forming dinoflagellate Alexandrium tamarense to prove the method. An algorithm was developed to automatically pinpoint just those metabolites with highly 13C-enriched isotope signatures, allowing us to discover algal exudates from the complex seawater background. The stable-isotope pattern (SIP of the detected metabolites then allowed for more accurate assignment to an empirical formula, a critical first step in their identification. This automated workflow provides an effective way to explore the chemical nature of the solutes exuded from phytoplankton cells and will facilitate the discovery of novel dissolved bioactive compounds.

  11. Postmortem interval estimation: a novel approach utilizing gas chromatography/mass spectrometry-based biochemical profiling.

    Science.gov (United States)

    Kaszynski, Richard H; Nishiumi, Shin; Azuma, Takeshi; Yoshida, Masaru; Kondo, Takeshi; Takahashi, Motonori; Asano, Migiwa; Ueno, Yasuhiro

    2016-05-01

    While the molecular mechanisms underlying postmortem change have been exhaustively investigated, the establishment of an objective and reliable means for estimating postmortem interval (PMI) remains an elusive feat. In the present study, we exploit low molecular weight metabolites to estimate postmortem interval in mice. After sacrifice, serum and muscle samples were procured from C57BL/6J mice (n = 52) at seven predetermined postmortem intervals (0, 1, 3, 6, 12, 24, and 48 h). After extraction and isolation, low molecular weight metabolites were measured via gas chromatography/mass spectrometry (GC/MS) and examined via semi-quantification studies. Then, PMI prediction models were generated for each of the 175 and 163 metabolites identified in muscle and serum, respectively, using a non-linear least squares curve fitting program. A PMI estimation panel for muscle and serum was then erected which consisted of 17 (9.7%) and 14 (8.5%) of the best PMI biomarkers identified in muscle and serum profiles demonstrating statistically significant correlations between metabolite quantity and PMI. Using a single-blinded assessment, we carried out validation studies on the PMI estimation panels. Mean ± standard deviation for accuracy of muscle and serum PMI prediction panels was -0.27 ± 2.88 and -0.89 ± 2.31 h, respectively. Ultimately, these studies elucidate the utility of metabolomic profiling in PMI estimation and pave the path toward biochemical profiling studies involving human samples.

  12. Mass Spectrometry-Based Biomarker Discovery.

    Science.gov (United States)

    Zhou, Weidong; Petricoin, Emanuel F; Longo, Caterina

    2017-01-01

    The discovery of candidate biomarkers within the entire proteome is one of the most important and challenging goals in proteomic research. Mass spectrometry-based proteomics is a modern and promising technology for semiquantitative and qualitative assessment of proteins, enabling protein sequencing and identification with exquisite accuracy and sensitivity. For mass spectrometry analysis, protein extractions from tissues or body fluids and subsequent protein fractionation represent an important and unavoidable step in the workflow for biomarker discovery. Following extraction of proteins, the protein mixture must be digested, reduced, alkylated, and cleaned up prior to mass spectrometry. The aim of our chapter is to provide comprehensible and practical lab procedures for sample digestion, protein fractionation, and subsequent mass spectrometry analysis.

  13. Oligosaccharide substrate preferences of human extracellular sulfatase Sulf2 using liquid chromatography-mass spectrometry based glycomics approaches.

    Directory of Open Access Journals (Sweden)

    Yu Huang

    Full Text Available Sulfs are extracellular endosulfatases that selectively remove the 6-O-sulfate groups from cell surface heparan sulfate (HS chain. By altering the sulfation at these particular sites, Sulfs function to remodel HS chains. As a result of the remodeling activity, HSulf2 regulates a multitude of cell-signaling events that depend on interactions between proteins and HS. Previous efforts to characterize the substrate specificity of human Sulfs (HSulfs focused on the analysis of HS disaccharides and synthetic repeating units. In this study, we characterized the substrate preferences of human HSulf2 using HS oligosaccharides with various lengths and sulfation degrees from several naturally occurring HS sources by applying liquid chromatography mass spectrometry based glycomics methods. The results showed that HSulf2 preferentially digests highly sulfated HS oligosaccharides with zero acetyl groups and this preference is length dependent. In terms of length of oligosaccharides, HSulf2 digestion induced more sulfation decrease on DP6 (DP: degree of polymerization compared to DP2, DP4 and DP8. In addition, the HSulf2 preferentially digests the oligosaccharide domain located at the non-reducing end (NRE of the HS and heparin chain. In addition, the HSulf2 digestion products were altered only for specific isomers. HSulf2 treated NRE oligosaccharides also showed greater decrease in cell proliferation than those from internal domains of the HS chain. After further chromatographic separation, we identified the three most preferred unsaturated hexasaccharide for HSulf2.

  14. Brute-Force Approach for Mass Spectrometry-Based Variant Peptide Identification in Proteogenomics without Personalized Genomic Data

    Science.gov (United States)

    Ivanov, Mark V.; Lobas, Anna A.; Levitsky, Lev I.; Moshkovskii, Sergei A.; Gorshkov, Mikhail V.

    2018-02-01

    In a proteogenomic approach based on tandem mass spectrometry analysis of proteolytic peptide mixtures, customized exome or RNA-seq databases are employed for identifying protein sequence variants. However, the problem of variant peptide identification without personalized genomic data is important for a variety of applications. Following the recent proposal by Chick et al. (Nat. Biotechnol. 33, 743-749, 2015) on the feasibility of such variant peptide search, we evaluated two available approaches based on the previously suggested "open" search and the "brute-force" strategy. To improve the efficiency of these approaches, we propose an algorithm for exclusion of false variant identifications from the search results involving analysis of modifications mimicking single amino acid substitutions. Also, we propose a de novo based scoring scheme for assessment of identified point mutations. In the scheme, the search engine analyzes y-type fragment ions in MS/MS spectra to confirm the location of the mutation in the variant peptide sequence.

  15. Vitroprocines, new antibiotics against Acinetobacter baumannii, discovered from marine Vibrio sp. QWI-06 using mass-spectrometry-based metabolomics approach

    Science.gov (United States)

    Liaw, Chih-Chuang; Chen, Pei-Chin; Shih, Chao-Jen; Tseng, Sung-Pin; Lai, Ying-Mi; Hsu, Chi-Hsin; Dorrestein, Pieter C.; Yang, Yu-Liang

    2015-08-01

    A robust and convenient research strategy integrating state-of-the-art analytical techniques is needed to efficiently discover novel compounds from marine microbial resources. In this study, we identified a series of amino-polyketide derivatives, vitroprocines A-J, from the marine bacterium Vibrio sp. QWI-06 by an integrated approach using imaging mass spectroscopy and molecular networking, as well as conventional bioactivity-guided fractionation and isolation. The structure-activity relationship of vitroprocines against Acinetobacter baumannii is proposed. In addition, feeding experiments with 13C-labeled precursors indicated that a pyridoxal 5‧-phosphate-dependent mechanism is involved in the biosynthesis of vitroprocines. Elucidation of amino-polyketide derivatives from a species of marine bacteria for the first time demonstrates the potential of this integrated metabolomics approach to uncover marine bacterial biodiversity.

  16. An efficient algorithmic approach for mass spectrometry-based disulfide connectivity determination using multi-ion analysis

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    Yen Ten-Yang

    2011-02-01

    Full Text Available Abstract Background Determining the disulfide (S-S bond pattern in a protein is often crucial for understanding its structure and function. In recent research, mass spectrometry (MS based analysis has been applied to this problem following protein digestion under both partial reduction and non-reduction conditions. However, this paradigm still awaits solutions to certain algorithmic problems fundamental amongst which is the efficient matching of an exponentially growing set of putative S-S bonded structural alternatives to the large amounts of experimental spectrometric data. Current methods circumvent this challenge primarily through simplifications, such as by assuming only the occurrence of certain ion-types (b-ions and y-ions that predominate in the more popular dissociation methods, such as collision-induced dissociation (CID. Unfortunately, this can adversely impact the quality of results. Method We present an algorithmic approach to this problem that can, with high computational efficiency, analyze multiple ions types (a, b, bo, b*, c, x, y, yo, y*, and z and deal with complex bonding topologies, such as inter/intra bonding involving more than two peptides. The proposed approach combines an approximation algorithm-based search formulation with data driven parameter estimation. This formulation considers only those regions of the search space where the correct solution resides with a high likelihood. Putative disulfide bonds thus obtained are finally combined in a globally consistent pattern to yield the overall disulfide bonding topology of the molecule. Additionally, each bond is associated with a confidence score, which aids in interpretation and assimilation of the results. Results The method was tested on nine different eukaryotic Glycosyltransferases possessing disulfide bonding topologies of varying complexity. Its performance was found to be characterized by high efficiency (in terms of time and the fraction of search space

  17. Recent advances in mass spectrometry-based approaches for proteomics and biologics: Great contribution for developing therapeutic antibodies.

    Science.gov (United States)

    Iwamoto, Noriko; Shimada, Takashi

    2018-05-01

    Since the turn of the century, mass spectrometry (MS) technologies have continued to improve dramatically, and advanced strategies that were impossible a decade ago are increasingly becoming available. The basic characteristics behind these advancements are MS resolution, quantitative accuracy, and information science for appropriate data processing. The spectral data from MS contain various types of information. The benefits of improving the resolution of MS data include accurate molecular structural-derived information, and as a result, we can obtain a refined biomolecular structure determination in a sequential and large-scale manner. Moreover, in MS data, not only accurate structural information but also the generated ion amount plays an important rule. This progress has greatly contributed a research field that captures biological events as a system by comprehensively tracing the various changes in biomolecular dynamics. The sequential changes of proteome expression in biological pathways are very essential, and the amounts of the changes often directly become the targets of drug discovery or indicators of clinical efficacy. To take this proteomic approach, it is necessary to separate the individual MS spectra derived from each biomolecule in the complexed biological samples. MS itself is not so infinite to perform the all peak separation, and we should consider improving the methods for sample processing and purification to make them suitable for injection into MS. The above-described characteristics can only be achieved using MS with any analytical instrument. Moreover, MS is expected to be applied and expand into many fields, not only basic life sciences but also forensic medicine, plant sciences, materials, and natural products. In this review, we focus on the technical fundamentals and future aspects of the strategies for accurate structural identification, structure-indicated quantitation, and on the challenges for pharmacokinetics of high

  18. Discovery of safety biomarkers for atorvastatin in rat urine using mass spectrometry based metabolomics combined with global and targeted approach

    International Nuclear Information System (INIS)

    Kumar, Bhowmik Salil; Lee, Young-Joo; Yi, Hong Jae; Chung, Bong Chul; Jung, Byung Hwa

    2010-01-01

    In order to develop a safety biomarker for atorvastatin, this drug was orally administrated to hyperlipidemic rats, and a metabolomic study was performed. Atorvastatin was given in doses of either 70 mg kg -1 day -1 or 250 mg kg -1 day -1 for a period of 7 days (n = 4 for each group). To evaluate any abnormal effects of the drug, physiological and plasma biochemical parameters were measured and histopathological tests were carried out. Safety biomarkers were derived by comparing these parameters and using both global and targeted metabolic profiling. Global metabolic profiling was performed using liquid chromatography/time of flight/mass spectrometry (LC/TOF/MS) with multivariate data analysis. Several safety biomarker candidates that included various steroids and amino acids were discovered as a result of global metabolic profiling, and they were also confirmed by targeted metabolic profiling using gas chromatography/mass spectrometry (GC/MS) and capillary electrophoresis/mass spectrometry (CE/MS). Serum biochemical and histopathological tests were used to detect abnormal drug reactions in the liver after repeating oral administration of atorvastatin. The metabolic differences between control and the drug-treated groups were compared using PLS-DA score plots. These results were compared with the physiological and plasma biochemical parameters and the results of a histopathological test. Estrone, cortisone, proline, cystine, 3-ureidopropionic acid and histidine were proposed as potential safety biomarkers related with the liver toxicity of atorvastatin. These results indicate that the combined application of global and targeted metabolic profiling could be a useful tool for the discovery of drug safety biomarkers.

  19. Discovery of safety biomarkers for atorvastatin in rat urine using mass spectrometry based metabolomics combined with global and targeted approach

    Energy Technology Data Exchange (ETDEWEB)

    Kumar, Bhowmik Salil [Bioanalysis and Biotransformation Research Center, Korea Institute of Science and Technology, P.O. Box 131, Cheongryang, Seoul 130-650 (Korea, Republic of); University of Science and Technology, (305-333) 113 Gwahangno, Yuseong-gu, Daejeon (Korea, Republic of); Lee, Young-Joo; Yi, Hong Jae [College of Pharmacy, Kyung Hee University, Hoegi-dong, Dongdaemun-gu, Seoul 130-791 (Korea, Republic of); Chung, Bong Chul [Bioanalysis and Biotransformation Research Center, Korea Institute of Science and Technology, P.O. Box 131, Cheongryang, Seoul 130-650 (Korea, Republic of); Jung, Byung Hwa, E-mail: jbhluck@kist.re.kr [Bioanalysis and Biotransformation Research Center, Korea Institute of Science and Technology, P.O. Box 131, Cheongryang, Seoul 130-650 (Korea, Republic of); University of Science and Technology, (305-333) 113 Gwahangno, Yuseong-gu, Daejeon (Korea, Republic of)

    2010-02-19

    In order to develop a safety biomarker for atorvastatin, this drug was orally administrated to hyperlipidemic rats, and a metabolomic study was performed. Atorvastatin was given in doses of either 70 mg kg{sup -1} day{sup -1} or 250 mg kg{sup -1} day{sup -1} for a period of 7 days (n = 4 for each group). To evaluate any abnormal effects of the drug, physiological and plasma biochemical parameters were measured and histopathological tests were carried out. Safety biomarkers were derived by comparing these parameters and using both global and targeted metabolic profiling. Global metabolic profiling was performed using liquid chromatography/time of flight/mass spectrometry (LC/TOF/MS) with multivariate data analysis. Several safety biomarker candidates that included various steroids and amino acids were discovered as a result of global metabolic profiling, and they were also confirmed by targeted metabolic profiling using gas chromatography/mass spectrometry (GC/MS) and capillary electrophoresis/mass spectrometry (CE/MS). Serum biochemical and histopathological tests were used to detect abnormal drug reactions in the liver after repeating oral administration of atorvastatin. The metabolic differences between control and the drug-treated groups were compared using PLS-DA score plots. These results were compared with the physiological and plasma biochemical parameters and the results of a histopathological test. Estrone, cortisone, proline, cystine, 3-ureidopropionic acid and histidine were proposed as potential safety biomarkers related with the liver toxicity of atorvastatin. These results indicate that the combined application of global and targeted metabolic profiling could be a useful tool for the discovery of drug safety biomarkers.

  20. Introduction to mass spectrometry-based proteomics

    DEFF Research Database (Denmark)

    Matthiesen, R.; Bunkenborg, J.

    2013-01-01

    Mass spectrometry has been widely applied to study biomolecules and one rapidly developing field is the global analysis of proteins, proteomics. Understanding and handling mass spectrometry data is a multifaceted task that requires many decisions to be made to get the most comprehensive informati...

  1. Fusion of mass spectrometry-based metabolomics data

    NARCIS (Netherlands)

    Smilde, Age K.; van der Werf, Mariët J.; Bijlsma, Sabina; van der Werff-van der Vat, Bianca J. C.; Jellema, Renger H.

    2005-01-01

    A general method is presented for combining mass spectrometry-based metabolomics data. Such data are becoming more and more abundant, and proper tools for fusing these types of data sets are needed. Fusion of metabolomics data leads to a comprehensive view on the metabolome of an organism or

  2. Dissecting plasmodesmata molecular composition by mass spectrometry-based proteomics.

    Directory of Open Access Journals (Sweden)

    Emmanuelle Maria Françoise Bayer

    2013-01-01

    Full Text Available In plants, the intercellular communication through the membranous channels called plasmodesmata (PD; singular plasmodesma plays pivotal roles in the orchestration of development, defence responses and viral propagation. PD are dynamic structures embedded in the plant cell wall that are defined by specialised domains of the endoplasmic reticulum and the plasma membrane. PD structure and unique functions are guaranteed by their particular molecular composition. Yet, up to recent years and despite numerous approaches such as mutant screens, immunolocalisation or screening of random cDNAs, only few PD proteins had been conclusively identified and characterised. A clear breakthrough in the search of PD constituents came from mass-spectrometry-based proteomic approaches coupled with subcellular fractionation strategies. Due to their position, firmly anchored in the extracellular matrix, PD are notoriously difficult to isolate for biochemical analysis. Proteomic-based approaches have therefore first relied on the use of cell wall fractions containing embedded PD then on free PD fractions whereby PD membranes were released from the walls by enzymatic degradation. To discriminate between likely contaminants and PD protein candidates, bioinformatics tools have often been used in combination with proteomic approaches. GFP fusion proteins of selected candidates have confirmed the PD association of several protein families. Here we review the accomplishments and limitations of the proteomic based strategies to unravel the functional and structural complexity of PD. We also discuss the role of the identified PD associated proteins.

  3. Dissecting plasmodesmata molecular composition by mass spectrometry-based proteomics.

    Science.gov (United States)

    Salmon, Magali S; Bayer, Emmanuelle M F

    2012-01-01

    In plants, the intercellular communication through the membranous channels called plasmodesmata (PD; singular plasmodesma) plays pivotal roles in the orchestration of development, defence responses, and viral propagation. PD are dynamic structures embedded in the plant cell wall that are defined by specialized domains of the endoplasmic reticulum (ER) and the plasma membrane (PM). PD structure and unique functions are guaranteed by their particular molecular composition. Yet, up to recent years and despite numerous approaches such as mutant screens, immunolocalization, or screening of random cDNAs, only few PD proteins had been conclusively identified and characterized. A clear breakthrough in the search of PD constituents came from mass-spectrometry-based proteomic approaches coupled with subcellular fractionation strategies. Due to their position, firmly anchored in the extracellular matrix, PD are notoriously difficult to isolate for biochemical analysis. Proteomic-based approaches have therefore first relied on the use of cell wall fractions containing embedded PD then on "free" PD fractions whereby PD membranes were released from the walls by enzymatic degradation. To discriminate between likely contaminants and PD protein candidates, bioinformatics tools have often been used in combination with proteomic approaches. GFP fusion proteins of selected candidates have confirmed the PD association of several protein families. Here we review the accomplishments and limitations of the proteomic-based strategies to unravel the functional and structural complexity of PD. We also discuss the role of the identified PD-associated proteins.

  4. Novel TIA biomarkers identified by mass spectrometry-based proteomics.

    Science.gov (United States)

    George, Paul M; Mlynash, Michael; Adams, Christopher M; Kuo, Calvin J; Albers, Gregory W; Olivot, Jean-Marc

    2015-12-01

    Transient ischemic attacks remain a clinical diagnosis with significant variability between physicians. Finding reliable biomarkers to identify transient ischemic attacks would improve patient care and optimize treatment. Our aim is to identify novel serum TIA biomarkers through the use of mass spectroscopy-based proteomics. Patients with transient neurologic symptoms were prospectively enrolled. Mass spectrometry-based proteomics, an unbiased method to identify candidate proteins, was used to test the serum of the patients for biomarkers of cerebral ischemia. Three candidate proteins were found, and serum concentrations of these proteins were measured by enzyme-linked immunosorbent assay in a second cohort of prospectively enrolled patients. The Student's t-test was used for comparison. The Benjamini-Hochberg false discovery rate controlling procedure for multiple comparison adjustments determined significance for the proteomic screen. Patients with transient ischemic attacks (n = 20), minor strokes (n = 15), and controls (i.e. migraine, seizure, n = 12) were enrolled in the first cohort. Ceruloplasmin, complement component C8 gamma (C8γ), and platelet basic protein were significantly different between the ischemic group (transient ischemic attack and minor stroke) and the controls (P = 0·0001, P = 0·00027, P = 0·00105, respectively). A second cohort of patients with transient ischemic attack (n = 22), minor stroke (n = 20), and controls' (n = 12) serum was enrolled. Platelet basic protein serum concentrations were increased in the ischemic samples compared with control (for transient ischemic attack alone, P = 0·019, for the ischemic group, P = 0·046). Ceruloplasmin trended towards increased concentrations in the ischemic group (P = 0·127); no significant difference in C8γ (P = 0·44) was found. Utilizing mass spectrometry-based proteomics, platelet basic protein has been identified as a candidate serum

  5. Centrosome isolation and analysis by mass spectrometry-based proteomics

    DEFF Research Database (Denmark)

    Jakobsen, Lis; Schrøder, Jacob Morville; Larsen, Katja M

    2013-01-01

    Centrioles are microtubule-based scaffolds that are essential for the formation of centrosomes, cilia, and flagella with important functions throughout the cell cycle, in physiology and during development. The ability to purify centriole-containing organelles on a large scale, combined with advan...... to isolate centrosomes from human cells and strategies to selectively identify and study the properties of the associated proteins using quantitative mass spectrometry-based proteomics.......Centrioles are microtubule-based scaffolds that are essential for the formation of centrosomes, cilia, and flagella with important functions throughout the cell cycle, in physiology and during development. The ability to purify centriole-containing organelles on a large scale, combined...... with advances in protein identification using mass spectrometry-based proteomics, have revealed multiple centriole-associated proteins that are conserved during evolution in eukaryotes. Despite these advances, the molecular basis for the plethora of processes coordinated by cilia and centrosomes is not fully...

  6. Application of mass spectrometry-based proteomics for biomarker discovery in neurological disorders

    Directory of Open Access Journals (Sweden)

    Venugopal Abhilash

    2009-01-01

    Full Text Available Mass spectrometry-based quantitative proteomics has emerged as a powerful approach that has the potential to accelerate biomarker discovery, both for diagnostic as well as therapeutic purposes. Proteomics has traditionally been synonymous with 2D gels but is increasingly shifting to the use of gel-free systems and liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS. Quantitative proteomic approaches have already been applied to investigate various neurological disorders, especially in the context of identifying biomarkers from cerebrospinal fluid and serum. This review highlights the scope of different applications of quantitative proteomics in understanding neurological disorders with special emphasis on biomarker discovery.

  7. Variability in Mass Spectrometry-based Quantification of Clinically Relevant Drug Transporters and Drug Metabolizing Enzymes

    NARCIS (Netherlands)

    Wegler, C.; Gaugaz, F.Z.; Andersson, T.B.; Wiśniewski, J.R.; Busch, D.; Gröer, C.; Oswald, S.; Norén, A.; Weiss, F.; Hammer, H.S.; Joos, T.O.; Poetz, O.; Achour, B.; Rostami-Hodjegan, A.; Steeg, E. van de; Wortelboer, H.M.; Artursson, P.

    2017-01-01

    Many different methods are used for mass-spectrometry-based protein quantification in pharmacokinetics and systems pharmacology. It has not been established to what extent the results from these various methods are comparable. Here, we compared six different mass spectrometry-based proteomics

  8. Simultaneous quantification of protein phosphorylation sites using liquid chromatography-tandem mass spectrometry-based targeted proteomics: a linear algebra approach for isobaric phosphopeptides.

    Science.gov (United States)

    Xu, Feifei; Yang, Ting; Sheng, Yuan; Zhong, Ting; Yang, Mi; Chen, Yun

    2014-12-05

    As one of the most studied post-translational modifications (PTM), protein phosphorylation plays an essential role in almost all cellular processes. Current methods are able to predict and determine thousands of phosphorylation sites, whereas stoichiometric quantification of these sites is still challenging. Liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS)-based targeted proteomics is emerging as a promising technique for site-specific quantification of protein phosphorylation using proteolytic peptides as surrogates of proteins. However, several issues may limit its application, one of which relates to the phosphopeptides with different phosphorylation sites and the same mass (i.e., isobaric phosphopeptides). While employment of site-specific product ions allows for these isobaric phosphopeptides to be distinguished and quantified, site-specific product ions are often absent or weak in tandem mass spectra. In this study, linear algebra algorithms were employed as an add-on to targeted proteomics to retrieve information on individual phosphopeptides from their common spectra. To achieve this simultaneous quantification, a LC-MS/MS-based targeted proteomics assay was first developed and validated for each phosphopeptide. Given the slope and intercept of calibration curves of phosphopeptides in each transition, linear algebraic equations were developed. Using a series of mock mixtures prepared with varying concentrations of each phosphopeptide, the reliability of the approach to quantify isobaric phosphopeptides containing multiple phosphorylation sites (≥ 2) was discussed. Finally, we applied this approach to determine the phosphorylation stoichiometry of heat shock protein 27 (HSP27) at Ser78 and Ser82 in breast cancer cells and tissue samples.

  9. MULTI-DIMENSIONAL MASS SPECTROMETRY-BASED SHOTGUN LIPIDOMICS AND NOVEL STRATEGIES FOR LIPIDOMIC ANALYSES

    Science.gov (United States)

    Han, Xianlin; Yang, Kui; Gross, Richard W.

    2011-01-01

    Since our last comprehensive review on multi-dimensional mass spectrometry-based shotgun lipidomics (Mass Spectrom. Rev. 24 (2005), 367), many new developments in the field of lipidomics have occurred. These developments include new strategies and refinements for shotgun lipidomic approaches that use direct infusion, including novel fragmentation strategies, identification of multiple new informative dimensions for mass spectrometric interrogation, and the development of new bioinformatic approaches for enhanced identification and quantitation of the individual molecular constituents that comprise each cell’s lipidome. Concurrently, advances in liquid chromatography-based platforms and novel strategies for quantitative matrix-assisted laser desorption/ionization mass spectrometry for lipidomic analyses have been developed. Through the synergistic use of this repertoire of new mass spectrometric approaches, the power and scope of lipidomics has been greatly expanded to accelerate progress toward the comprehensive understanding of the pleiotropic roles of lipids in biological systems. PMID:21755525

  10. Analytical strategies in mass spectrometry-based phosphoproteomics

    DEFF Research Database (Denmark)

    Rosenqvist, Heidi; Ye, Juanying; Jensen, Ole N

    2011-01-01

    then discuss various tandem mass spectrometry approaches for phosphopeptide sequencing and quantification, and we consider aspects of phosphoproteome data analysis and interpretation. Efficient integration of these stages of phosphoproteome analysis is highly important to ensure a successful outcome of large...

  11. Gas chromatography-mass spectrometry based metabolomic approach for optimization and toxicity evaluation of earthworm sub-lethal responses to carbofuran.

    Directory of Open Access Journals (Sweden)

    Mohana Krishna Reddy Mudiam

    Full Text Available Despite recent advances in understanding mechanism of toxicity, the development of biomarkers (biochemicals that vary significantly with exposure to chemicals for pesticides and environmental contaminants exposure is still a challenging task. Carbofuran is one of the most commonly used pesticides in agriculture and said to be most toxic carbamate pesticide. It is necessary to identify the biochemicals that can vary significantly after carbofuran exposure on earthworms which will help to assess the soil ecotoxicity. Initially, we have optimized the extraction conditions which are suitable for high-throughput gas chromatography mass spectrometry (GC-MS based metabolomics for the tissue of earthworm, Metaphire posthuma. Upon evaluation of five different extraction solvent systems, 80% methanol was found to have good extraction efficiency based on the yields of metabolites, multivariate analysis, total number of peaks and reproducibility of metabolites. Later the toxicity evaluation was performed to characterize the tissue specific metabolomic perturbation of earthworm, Metaphire posthuma after exposure to carbofuran at three different concentration levels (0.15, 0.3 and 0.6 mg/kg of soil. Seventeen metabolites, contributing to the best classification performance of highest dose dependent carbofuran exposed earthworms from healthy controls were identified. This study suggests that GC-MS based metabolomic approach was precise and sensitive to measure the earthworm responses to carbofuran exposure in soil, and can be used as a promising tool for environmental eco-toxicological studies.

  12. The collaboratory for MS3D: a new cyberinfrastructure for the structural elucidation of biological macromolecules and their assemblies using mass spectrometry-based approaches.

    Science.gov (United States)

    Yu, Eizadora T; Hawkins, Arie; Kuntz, Irwin D; Rahn, Larry A; Rothfuss, Andrew; Sale, Kenneth; Young, Malin M; Yang, Christine L; Pancerella, Carmen M; Fabris, Daniele

    2008-11-01

    Modern biomedical research is evolving with the rapid growth of diverse data types, biophysical characterization methods, computational tools and extensive collaboration among researchers spanning various communities and having complementary backgrounds and expertise. Collaborating researchers are increasingly dependent on shared data and tools made available by other investigators with common interests, thus forming communities that transcend the traditional boundaries of the single research laboratory or institution. Barriers, however, remain to the formation of these virtual communities, usually due to the steep learning curve associated with becoming familiar with new tools, or with the difficulties associated with transferring data between tools. Recognizing the need for shared reference data and analysis tools, we are developing an integrated knowledge environment that supports productive interactions among researchers. Here we report on our current collaborative environment, which focuses on bringing together structural biologists working in the area of mass spectrometric based methods for the analysis of tertiary and quaternary macromolecular structures (MS3D) called the Collaboratory for MS3D (C-MS3D). C-MS3D is a Web-portal designed to provide collaborators with a shared work environment that integrates data storage and management with data analysis tools. Files are stored and archived along with pertinent meta data in such a way as to allow file handling to be tracked (data provenance) and data files to be searched using keywords and modification dates. While at this time the portal is designed around a specific application, the shared work environment is a general approach to building collaborative work groups. The goal of this is to not only provide a common data sharing and archiving system, but also to assist in the building of new collaborations and to spur the development of new tools and technologies.

  13. Assessment of protein modifications in liver of rats under chronic treatment with paracetamol (acetaminophen) using two complementary mass spectrometry-based metabolomic approaches.

    Science.gov (United States)

    Mast, Carole; Lyan, Bernard; Joly, Charlotte; Centeno, Delphine; Giacomoni, Franck; Martin, Jean-François; Mosoni, Laurent; Dardevet, Dominique; Pujos-Guillot, Estelle; Papet, Isabelle

    2015-04-29

    Liver protein can be altered under paracetamol (APAP) treatment. APAP-protein adducts and other protein modifications (oxidation/nitration, expression) play a role in hepatotoxicity induced by acute overdoses, but it is unknown whether liver protein modifications occur during long-term treatment with non-toxic doses of APAP. We quantified APAP-protein adducts and assessed other protein modifications in the liver from rats under chronic (17 days) treatment with two APAP doses (0.5% or 1% of APAP in the diet w/w). A targeted metabolomic method was validated and used to quantify APAP-protein adducts as APAP-cysteine adducts following proteolytic hydrolysis. The limit of detection was found to be 7ng APAP-cysteine/mL hydrolysate i.e. an APAP-Cys to tyrosine ratio of 0.016‰. Other protein modifications were assessed on the same protein hydrolysate by untargeted metabolomics including a new strategy to process the data and identify discriminant molecules. These two complementary mass spectrometry (MS)-based metabolic approaches enabled the assessment of a wide range of protein modifications induced by chronic treatment with APAP. APAP-protein adducts were detected even in the absence of glutathione depletion and hepatotoxicity, i.e. in the 0.5% APAP group, and increased by 218% in the 1% APAP group compared to the 0.5% APAP group. At the same time, the untargeted metabolomic method revealed a decrease in the binding of cysteine, cysteinyl-glycine and GSH to thiol groups of protein cysteine residues, an increase in the oxidation of tryptophan and proline residues and a modification in protein expression. This wide range of modifications in liver proteins occurred in rats under chronic treatment with APAP that did not induce hepatotoxicity. Copyright © 2015 Elsevier B.V. All rights reserved.

  14. Rapid resolution liquid chromatography coupled with quadrupole time-of-flight mass spectrometry-based metabolomics approach to study the effects of jieduquyuziyin prescription on systemic lupus erythematosus.

    Science.gov (United States)

    Ding, Xinghong; Hu, Jinbo; Wen, Chengping; Ding, Zhishan; Yao, Li; Fan, Yongsheng

    2014-01-01

    Jieduquyuziyin prescription (JP), a traditional Chinese medicine (TCM) prescription, has been widely used for the clinical treatment of systemic lupus erythematosus (SLE). However, the complex chemical constituents of JP and the multifactorial pathogenesis of SLE make research on the therapeutic mechanism of JP in SLE challenging. In this paper, a serum metabolomics approach based on rapid resolution liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (RRLC-Q-TOF/MS) was employed to acquire the metabolic characteristics of serum samples obtained from mice in the SLE model group, JP-treated group, prednisone acetate (PA)-treated group and control group. The orthogonal partial least squares (OPLS) was applied to recognize metabolic patterns, and an obvious separation of groups was obtained. Thirteen metabolites, namely, phosphatidylethanolamine (PE 20:3), hepoxilin B3, lyso- phosphatidylethanolamine (lyso-PE 22:6), 12S-hydroxypentaenoic acid (12S-HEPE), traumatic acid, serotonin, platelet-activating factor (PAF), phosphatidylcholine (PC 20:5),eicosapentaenoic acid (EPA), 12(S)-hydroxyei- cosatetraenoic acid (12S-HETE), 14-hydroxy docosahexaenoic acid (14-HDOHE), lyso-phosphatidylcholine (lyso-PC 20:4), and indole acetaldehyde, were identified and characterized as differential metabolites involved in the pathogenesis of SLE. After treatment with JP, the relative content of 12(S)-HETE, PAF, 12(S)-HEPE, EPA, PE (20:3), Lyso-PE(22:6), and 14-HDOHE were effectively regulated, which suggested that the therapeutic effects of JP on SLE may involve regulating disturbances to the metabolism of unsaturated fatty acid, tryptophan and phospholipid. This research also demonstrated that metabolomics is a powerful tool for researching complex disease mechanisms and evaluating the mechanism of action of TCM.

  15. Mass Spectrometry-Based Proteomics in Molecular Diagnostics: Discovery of Cancer Biomarkers Using Tissue Culture

    Science.gov (United States)

    Paul, Debasish; Kumar, Avinash; Gajbhiye, Akshada; Santra, Manas K.; Srikanth, Rapole

    2013-01-01

    Accurate diagnosis and proper monitoring of cancer patients remain a key obstacle for successful cancer treatment and prevention. Therein comes the need for biomarker discovery, which is crucial to the current oncological and other clinical practices having the potential to impact the diagnosis and prognosis. In fact, most of the biomarkers have been discovered utilizing the proteomics-based approaches. Although high-throughput mass spectrometry-based proteomic approaches like SILAC, 2D-DIGE, and iTRAQ are filling up the pitfalls of the conventional techniques, still serum proteomics importunately poses hurdle in overcoming a wide range of protein concentrations, and also the availability of patient tissue samples is a limitation for the biomarker discovery. Thus, researchers have looked for alternatives, and profiling of candidate biomarkers through tissue culture of tumor cell lines comes up as a promising option. It is a rich source of tumor cell-derived proteins, thereby, representing a wide array of potential biomarkers. Interestingly, most of the clinical biomarkers in use today (CA 125, CA 15.3, CA 19.9, and PSA) were discovered through tissue culture-based system and tissue extracts. This paper tries to emphasize the tissue culture-based discovery of candidate biomarkers through various mass spectrometry-based proteomic approaches. PMID:23586059

  16. Mass Spectrometry-Based Proteomics in Molecular Diagnostics: Discovery of Cancer Biomarkers Using Tissue Culture

    Directory of Open Access Journals (Sweden)

    Debasish Paul

    2013-01-01

    Full Text Available Accurate diagnosis and proper monitoring of cancer patients remain a key obstacle for successful cancer treatment and prevention. Therein comes the need for biomarker discovery, which is crucial to the current oncological and other clinical practices having the potential to impact the diagnosis and prognosis. In fact, most of the biomarkers have been discovered utilizing the proteomics-based approaches. Although high-throughput mass spectrometry-based proteomic approaches like SILAC, 2D-DIGE, and iTRAQ are filling up the pitfalls of the conventional techniques, still serum proteomics importunately poses hurdle in overcoming a wide range of protein concentrations, and also the availability of patient tissue samples is a limitation for the biomarker discovery. Thus, researchers have looked for alternatives, and profiling of candidate biomarkers through tissue culture of tumor cell lines comes up as a promising option. It is a rich source of tumor cell-derived proteins, thereby, representing a wide array of potential biomarkers. Interestingly, most of the clinical biomarkers in use today (CA 125, CA 15.3, CA 19.9, and PSA were discovered through tissue culture-based system and tissue extracts. This paper tries to emphasize the tissue culture-based discovery of candidate biomarkers through various mass spectrometry-based proteomic approaches.

  17. Mass Spectrometry Based Lipidomics: An Overview of Technological Platforms

    Science.gov (United States)

    Köfeler, Harald C.; Fauland, Alexander; Rechberger, Gerald N.; Trötzmüller, Martin

    2012-01-01

    One decade after the genomic and the proteomic life science revolution, new ‘omics’ fields are emerging. The metabolome encompasses the entity of small molecules—Most often end products of a catalytic process regulated by genes and proteins—with the lipidome being its fat soluble subdivision. Within recent years, lipids are more and more regarded not only as energy storage compounds but also as interactive players in various cellular regulation cycles and thus attain rising interest in the bio-medical community. The field of lipidomics is, on one hand, fuelled by analytical technology advances, particularly mass spectrometry and chromatography, but on the other hand new biological questions also drive analytical technology developments. Compared to fairly standardized genomic or proteomic high-throughput protocols, the high degree of molecular heterogeneity adds a special analytical challenge to lipidomic analysis. In this review, we will take a closer look at various mass spectrometric platforms for lipidomic analysis. We will focus on the advantages and limitations of various experimental setups like ‘shotgun lipidomics’, liquid chromatography—Mass spectrometry (LC-MS) and matrix assisted laser desorption ionization-time of flight (MALDI-TOF) based approaches. We will also examine available software packages for data analysis, which nowadays is in fact the rate limiting step for most ‘omics’ workflows. PMID:24957366

  18. Mass Spectrometry Based Lipidomics: An Overview of Technological Platforms

    Directory of Open Access Journals (Sweden)

    Harald C. Köfeler

    2012-01-01

    Full Text Available One decade after the genomic and the proteomic life science revolution, new ‘omics’ fields are emerging. The metabolome encompasses the entity of small molecules—Most often end products of a catalytic process regulated by genes and proteins—with the lipidome being its fat soluble subdivision. Within recent years, lipids are more and more regarded not only as energy storage compounds but also as interactive players in various cellular regulation cycles and thus attain rising interest in the bio-medical community. The field of lipidomics is, on one hand, fuelled by analytical technology advances, particularly mass spectrometry and chromatography, but on the other hand new biological questions also drive analytical technology developments. Compared to fairly standardized genomic or proteomic high-throughput protocols, the high degree of molecular heterogeneity adds a special analytical challenge to lipidomic analysis. In this review, we will take a closer look at various mass spectrometric platforms for lipidomic analysis. We will focus on the advantages and limitations of various experimental setups like ‘shotgun lipidomics’, liquid chromatography—Mass spectrometry (LC-MS and matrix assisted laser desorption ionization-time of flight (MALDI-TOF based approaches. We will also examine available software packages for data analysis, which nowadays is in fact the rate limiting step for most ‘omics’ workflows.

  19. Guidelines for reporting quantitative mass spectrometry based experiments in proteomics.

    Science.gov (United States)

    Martínez-Bartolomé, Salvador; Deutsch, Eric W; Binz, Pierre-Alain; Jones, Andrew R; Eisenacher, Martin; Mayer, Gerhard; Campos, Alex; Canals, Francesc; Bech-Serra, Joan-Josep; Carrascal, Montserrat; Gay, Marina; Paradela, Alberto; Navajas, Rosana; Marcilla, Miguel; Hernáez, María Luisa; Gutiérrez-Blázquez, María Dolores; Velarde, Luis Felipe Clemente; Aloria, Kerman; Beaskoetxea, Jabier; Medina-Aunon, J Alberto; Albar, Juan P

    2013-12-16

    Mass spectrometry is already a well-established protein identification tool and recent methodological and technological developments have also made possible the extraction of quantitative data of protein abundance in large-scale studies. Several strategies for absolute and relative quantitative proteomics and the statistical assessment of quantifications are possible, each having specific measurements and therefore, different data analysis workflows. The guidelines for Mass Spectrometry Quantification allow the description of a wide range of quantitative approaches, including labeled and label-free techniques and also targeted approaches such as Selected Reaction Monitoring (SRM). The HUPO Proteomics Standards Initiative (HUPO-PSI) has invested considerable efforts to improve the standardization of proteomics data handling, representation and sharing through the development of data standards, reporting guidelines, controlled vocabularies and tooling. In this manuscript, we describe a key output from the HUPO-PSI-namely the MIAPE Quant guidelines, which have developed in parallel with the corresponding data exchange format mzQuantML [1]. The MIAPE Quant guidelines describe the HUPO-PSI proposal concerning the minimum information to be reported when a quantitative data set, derived from mass spectrometry (MS), is submitted to a database or as supplementary information to a journal. The guidelines have been developed with input from a broad spectrum of stakeholders in the proteomics field to represent a true consensus view of the most important data types and metadata, required for a quantitative experiment to be analyzed critically or a data analysis pipeline to be reproduced. It is anticipated that they will influence or be directly adopted as part of journal guidelines for publication and by public proteomics databases and thus may have an impact on proteomics laboratories across the world. This article is part of a Special Issue entitled: Standardization and

  20. Probing Conformational Changes of Human DNA Polymerase λ Using Mass Spectrometry-Based Protein Footprinting

    Science.gov (United States)

    Fowler, Jason D.; Brown, Jessica A.; Kvaratskhelia, Mamuka; Suo, Zucai

    2009-01-01

    SUMMARY Crystallographic studies of the C-terminal, DNA polymerase β-like domain of human DNA polymerase lambda (fPolλ) suggested that the catalytic cycle might not involve a large protein domain rearrangement as observed with several replicative DNA polymerases and DNA polymerase β. To examine solution-phase protein conformation changes in fPolλ, which also contains a breast cancer susceptibility gene 1 C-terminal domain and a Proline-rich domain at its N-terminus, we used a mass spectrometry - based protein footprinting approach. In parallel experiments, surface accessibility maps for Arg residues were compared for the free fPolλ versus the binary complex of enzyme•gapped DNA and the ternary complex of enzyme•gapped DNA•dNTP. These experiments suggested that fPolλ does not undergo major conformational changes during the catalysis in the solution phase. Furthermore, the mass spectrometry-based protein footprinting experiments revealed that active site residue R386 was shielded from the surface only in the presence of both a gapped DNA substrate and an incoming nucleotide dNTP. Site-directed mutagenesis and pre-steady state kinetic studies confirmed the importance of R386 for the enzyme activity, and indicated the key role for its guanidino group in stabilizing the negative charges of an incoming nucleotide and the leaving pyrophosphate product. We suggest that such interactions could be shared by and important for catalytic functions of other DNA polymerases. PMID:19467241

  1. Advantages and Pitfalls of Mass Spectrometry Based Metabolome Profiling in Systems Biology.

    Science.gov (United States)

    Aretz, Ina; Meierhofer, David

    2016-04-27

    Mass spectrometry-based metabolome profiling became the method of choice in systems biology approaches and aims to enhance biological understanding of complex biological systems. Genomics, transcriptomics, and proteomics are well established technologies and are commonly used by many scientists. In comparison, metabolomics is an emerging field and has not reached such high-throughput, routine and coverage than other omics technologies. Nevertheless, substantial improvements were achieved during the last years. Integrated data derived from multi-omics approaches will provide a deeper understanding of entire biological systems. Metabolome profiling is mainly hampered by its diversity, variation of metabolite concentration by several orders of magnitude and biological data interpretation. Thus, multiple approaches are required to cover most of the metabolites. No software tool is capable of comprehensively translating all the data into a biologically meaningful context yet. In this review, we discuss the advantages of metabolome profiling and main obstacles limiting progress in systems biology.

  2. Advantages and Pitfalls of Mass Spectrometry Based Metabolome Profiling in Systems Biology

    Directory of Open Access Journals (Sweden)

    Ina Aretz

    2016-04-01

    Full Text Available Mass spectrometry-based metabolome profiling became the method of choice in systems biology approaches and aims to enhance biological understanding of complex biological systems. Genomics, transcriptomics, and proteomics are well established technologies and are commonly used by many scientists. In comparison, metabolomics is an emerging field and has not reached such high-throughput, routine and coverage than other omics technologies. Nevertheless, substantial improvements were achieved during the last years. Integrated data derived from multi-omics approaches will provide a deeper understanding of entire biological systems. Metabolome profiling is mainly hampered by its diversity, variation of metabolite concentration by several orders of magnitude and biological data interpretation. Thus, multiple approaches are required to cover most of the metabolites. No software tool is capable of comprehensively translating all the data into a biologically meaningful context yet. In this review, we discuss the advantages of metabolome profiling and main obstacles limiting progress in systems biology.

  3. Mass spectrometry-based metabolomics for tuberculosis meningitis.

    Science.gov (United States)

    Zhang, Peixu; Zhang, Weiguanliu; Lang, Yue; Qu, Yan; Chu, Fengna; Chen, Jiafeng; Cui, Li

    2018-04-18

    Tuberculosis meningitis (TBM) is a prevalent form of extra-pulmonary tuberculosis that causes substantial morbidity and mortality. Diagnosis of TBM is difficult because of the limited sensitivity of existing laboratory techniques. A metabolomics approach can be used to investigate the sets of metabolites of both bacteria and host, and has been used to clarify the mechanisms underlying disease development, and identify metabolic changes, leadings to improved methods for diagnosis, treatment, and prognostication. Mass spectrometry (MS) is a major analysis platform used in metabolomics, and MS-based metabolomics provides wide metabolite coverage, because of its high sensitivity, and is useful for the investigation of Mycobacterium tuberculosis (Mtb) and related diseases. It has been used to investigate TBM diagnosis; however, the processes involved in the MS-based metabolomics approach are complex and flexible, and often consist of several steps, and small changes in the methods used can have a huge impact on the final results. Here, the process of MS-based metabolomics is summarized and its applications in Mtb and Mtb-related diseases discussed. Moreover, the current status of TBM metabolomics is described. Copyright © 2018. Published by Elsevier B.V.

  4. Statistical methods for mass spectrometry-based clinical proteomics

    NARCIS (Netherlands)

    Kakourou, A.

    2018-01-01

    The work presented in this thesis focuses on methods for the construction of diagnostic rules based on clinical mass spectrometry proteomic data. Mass spectrometry has become one of the key technologies for jointly measuring the expression of thousands of proteins in biological samples.

  5. Quantification in untargeted mass spectrometry-based metabolomics

    NARCIS (Netherlands)

    Kloet, Frans Meindert van der

    2014-01-01

    The aim of this thesis was to develop concepts and methods to extract qualitative and quantitative information about metabolites from untargeted mass spectrometric data of biological samples. Several typical challenges in data handling were addressed that prevent a straightforward interpretation

  6. Mass spectrometry based proteomics profiling as diagnostic tool in oncology: current status and future perspective.

    Science.gov (United States)

    Findeisen, Peter; Neumaier, Michael

    2009-01-01

    Proteomics analysis has been heralded as a novel tool for identifying new and specific biomarkers that may improve diagnosis and monitoring of various disease states. Recent years have brought a number of proteomics profiling technologies. Although proteomics profiling has resulted in the detection of disease-associated differences and modification of proteins, current proteomics technologies display certain limitations that are hampering the introduction of these new technologies into clinical laboratory diagnostics and routine applications. In this review, we summarize current advances in mass spectrometry based biomarker discovery. The promises and challenges of this new technology are discussed with particular emphasis on diagnostic perspectives of mass-spectrometry based proteomics profiling for malignant diseases.

  7. Mass spectrometry-based analysis of whole-grain phytochemicals.

    Science.gov (United States)

    Koistinen, Ville Mikael; Hanhineva, Kati

    2017-05-24

    Whole grains are a rich source of several classes of phytochemicals, such as alkylresorcinols, benzoxazinoids, flavonoids, lignans, and phytosterols. A high intake of whole grains has been linked to a reduced risk of some major noncommunicable diseases, and it has been postulated that a complex mixture of phytochemicals works in synergy to generate beneficial health effects. Mass spectrometry, especially when coupled with liquid chromatography, is a widely used method for the analysis of phytochemicals owing to its high sensitivity and dynamic range. In this review, the current knowledge of the mass spectral properties of the most important classes of phytochemicals found in cereals of common wheat, barley, oats, and rye is discussed.

  8. Mass Spectrometry-Based N-Glycomics of Colorectal Cancer

    Directory of Open Access Journals (Sweden)

    Manveen K. Sethi

    2015-12-01

    Full Text Available Colorectal cancer (CRC is one of the most prevalent cancers worldwide. An increased molecular understanding of the CRC pathology is warranted to gain insights into the underlying molecular and cellular mechanisms of the disease. Altered protein glycosylation patterns are associated with most diseases including malignant transformation. Recent advances in mass spectrometry and bioinformatics have accelerated glycomics research and present a new paradigm for cancer biomarker discovery. Mass spectrometry (MS-based glycoproteomics and glycomics, therefore, hold considerable promise to improve the discovery of novel biomarkers with utility in disease diagnosis and therapy. This review focuses on the emerging field of glycomics to present a comprehensive review of advances in technologies and their application in studies aimed at discovering novel glycan-based biomarkers. We will also discuss some of the challenges associated with using glycans as biomarkers.

  9. Mass spectrometry based proteomics in cell biology and signaling research

    International Nuclear Information System (INIS)

    Mann, M.; Andersen, J.; Ishihama, Y.; Rappsilber, J.; Ong, S.; Foster, L.; Blagoev, B.; Kratchmarova, I.; Lasonder, E.

    2002-01-01

    Full text: Proteomics is one of the most powerful post-genomics technologies. Recently accomplishments include large scale protein-protein interaction mapping, large scale mapping of phosphorylation sites and the cloning of key signaling molecules. In this talk, current state of the art of the technology will be reviewed. Applications of proteomics to the mapping of multiprotein complexes will be illustrated with recent work on the spliceosome and the nucleolus. More than 300 proteins have been mapped to each of these complexes. Quantitative techniques are becoming more and more essential in proteomics. They are usually performed by the incorporation of stable isotopes - a light form in cell state 'A' and a heavy form in cell state 'E' - and subsequent comparison of mass spectrometric peak heights. A new technique called, SILAC for Stable isotope Incorporation by Amino acids in Cell culture, has been applied to studying cell differentiation and mapping secreted proteins from adipocytes. A number of known and novel proteins important in adipocyte differentiation have been identified by this technique. Some of these proved to be upregulated at the 1 mRNA level, too, whereas others appear to be regulated post-translationally. We have also applied the SILAC method to protein-protein interaction mapping. For example, we compared immunoprecipitates from stimulated and non-stimulated cells to find binding partners recruited to the bait due to the stimulus. Several novel substrates in the EGF pathway were found in this way. An important application of proteomics in the signaling field is the mapping of post-translational modifications. In particular, there are a number of techniques for phosphotyrosine phosphorylation mapping which have proven very useful. Making use of the mass deficiency of the phosphogroup, 'parent ion scans' con be performed, which selectively reveal phosphotyrosine peptides from complex peptides mixtures. This technique has been used to clone several

  10. Mass spectrometry-based proteomic quest for diabetes biomarkers.

    Science.gov (United States)

    Shao, Shiying; Guo, Tiannan; Aebersold, Ruedi

    2015-06-01

    Diabetes mellitus (DM) is a metabolic disorder characterized by chronic hyperglycemia, which affects hundreds of millions of individuals worldwide. Early diagnosis and complication prevention of DM are helpful for disease treatment. However, currently available DM diagnostic markers fail to achieve the goals. Identification of new diabetic biomarkers assisted by mass spectrometry (MS)-based proteomics may offer solution for the clinical challenges. Here, we review the current status of biomarker discovery in DM, and describe the pressure cycling technology (PCT)-Sequential Window Acquisition of all Theoretical fragment-ion (SWATH) workflow for sample-processing, biomarker discovery and validation, which may accelerate the current quest for DM biomarkers. This article is part of a Special Issue entitled: Medical Proteomics. Copyright © 2014 Elsevier B.V. All rights reserved.

  11. Decoding signalling networks by mass spectrometry-based proteomics

    DEFF Research Database (Denmark)

    Choudhary, Chuna Ram; Mann, Matthias

    2010-01-01

    Signalling networks regulate essentially all of the biology of cells and organisms in normal and disease states. Signalling is often studied using antibody-based techniques such as western blots. Large-scale 'precision proteomics' based on mass spectrometry now enables the system......-wide characterization of signalling events at the levels of post-translational modifications, protein-protein interactions and changes in protein expression. This technology delivers accurate and unbiased information about the quantitative changes of thousands of proteins and their modifications in response to any...... perturbation. Current studies focus on phosphorylation, but acetylation, methylation, glycosylation and ubiquitylation are also becoming amenable to investigation. Large-scale proteomics-based signalling research will fundamentally change our understanding of signalling networks....

  12. MSQuant, an Open Source Platform for Mass Spectrometry-Based Quantitative Proteomics

    DEFF Research Database (Denmark)

    Mortensen, Peter; Gouw, Joost W; Olsen, Jesper V

    2010-01-01

    Mass spectrometry-based proteomics critically depends on algorithms for data interpretation. A current bottleneck in the rapid advance of proteomics technology is the closed nature and slow development cycle of vendor-supplied software solutions. We have created an open source software environment...

  13. Effective representation and storage of mass spectrometry-based proteomic data sets for the scientific community

    DEFF Research Database (Denmark)

    Olsen, Jesper V; Mann, Matthias

    2011-01-01

    Mass spectrometry-based proteomics has emerged as a technology of choice for global analysis of cell signaling networks. However, reporting and sharing of MS data are often haphazard, limiting the usefulness of proteomics to the signaling community. We argue that raw data should always be provided...... mechanisms for community-wide sharing of these data....

  14. Biomarker discovery in mass spectrometry-based urinary proteomics.

    Science.gov (United States)

    Thomas, Samuel; Hao, Ling; Ricke, William A; Li, Lingjun

    2016-04-01

    Urinary proteomics has become one of the most attractive topics in disease biomarker discovery. MS-based proteomic analysis has advanced continuously and emerged as a prominent tool in the field of clinical bioanalysis. However, only few protein biomarkers have made their way to validation and clinical practice. Biomarker discovery is challenged by many clinical and analytical factors including, but not limited to, the complexity of urine and the wide dynamic range of endogenous proteins in the sample. This article highlights promising technologies and strategies in the MS-based biomarker discovery process, including study design, sample preparation, protein quantification, instrumental platforms, and bioinformatics. Different proteomics approaches are discussed, and progresses in maximizing urinary proteome coverage and standardization are emphasized in this review. MS-based urinary proteomics has great potential in the development of noninvasive diagnostic assays in the future, which will require collaborative efforts between analytical scientists, systems biologists, and clinicians. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  15. Liquid chromatography-mass spectrometry-based quantitative proteomics.

    Science.gov (United States)

    Linscheid, Michael W; Ahrends, Robert; Pieper, Stefan; Kühn, Andreas

    2009-01-01

    During the last decades, molecular sciences revolutionized biomedical research and gave rise to the biotechnology industry. During the next decades, the application of the quantitative sciences--informatics, physics, chemistry, and engineering--to biomedical research brings about the next revolution that will improve human healthcare and certainly create new technologies, since there is no doubt that small changes can have great effects. It is not a question of "yes" or "no," but of "how much," to make best use of the medical options we will have. In this context, the development of accurate analytical methods must be considered a cornerstone, since the understanding of biological processes will be impossible without information about the minute changes induced in cells by interactions of cell constituents with all sorts of endogenous and exogenous influences and disturbances. The first quantitative techniques, which were developed, allowed monitoring relative changes only, but they clearly showed the significance of the information obtained. The recent advent of techniques claiming to quantify proteins and peptides not only relative to each other, but also in an absolute fashion, promised another quantum leap, since knowing the absolute amount will allow comparing even unrelated species and the definition of parameters will permit to model biological systems much more accurate than before. To bring these promises to life, several approaches are under development at this point in time and this review is focused on those developments.

  16. History of inductively coupled plasma mass spectrometry-based immunoassays

    International Nuclear Information System (INIS)

    Giesen, Charlotte; Waentig, Larissa; Panne, Ulrich; Jakubowski, Norbert

    2012-01-01

    The analysis of biomolecules requires highly sensitive and selective detection methods capable of tolerating a complex, biological matrix. First applications of biomolecule detection by ICP-MS relied on the use of heteroelements as a label for quantification. However, the combination of immunoassays and ICP-MS facilitates multiparametric analyses through elemental tagging, and provides a powerful alternative to common bioanalytical methods. This approach extends the detection of biomarkers in clinical diagnosis, and has the potential to provide a deeper understanding of the investigated biological system. The results might lead to the detection of diseases at an early stage, or guide treatment plans. Immunoassays are well accepted and established for diagnostic purposes, albeit ICP-MS is scarcely applied for the detection of immune-based assays. However, the screening of biomarkers demands high throughput and multiplex/multiparametric techniques, considering the variety of analytes to be queried. Finally, quantitative information on the expression level of biomarkers is highly desirable to identify abnormalities in a given organism. Thus, it is the aim of this review to introduce the fundamentals, and to discuss the enormous strength of ICP-MS for the detection of different immunoassays on the basis of selected applications, with a special focus on LA‐ICP‐MS. - Highlights: ► We discuss the fundamentals of elemental tagging for ICP‐MS applications. ► We propose a definition for the expressions “label” and “tag”. ► We highlight LA‐ICP‐MS‐based heteroelement detection. ► We give an historic overview on ICP-MS and LA‐ICP‐MS-based immunoassays. ► In a personal outlook, we discuss future improvements realistically attainable.

  17. Biomarkers of systemic lupus erythematosus identified using mass spectrometry-based proteomics: a systematic review.

    Science.gov (United States)

    Nicolaou, Orthodoxia; Kousios, Andreas; Hadjisavvas, Andreas; Lauwerys, Bernard; Sokratous, Kleitos; Kyriacou, Kyriacos

    2017-05-01

    Advances in mass spectrometry technologies have created new opportunities for discovering novel protein biomarkers in systemic lupus erythematosus (SLE). We performed a systematic review of published reports on proteomic biomarkers identified in SLE patients using mass spectrometry-based proteomics and highlight their potential disease association and clinical utility. Two electronic databases, MEDLINE and EMBASE, were systematically searched up to July 2015. The methodological quality of studies included in the review was performed according to Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. Twenty-five studies were included in the review, identifying 241 SLE candidate proteomic biomarkers related to various aspects of the disease including disease diagnosis and activity or pinpointing specific organ involvement. Furthermore, 13 of the 25 studies validated their results for a selected number of biomarkers in an independent cohort, resulting in the validation of 28 candidate biomarkers. It is noteworthy that 11 candidate biomarkers were identified in more than one study. A significant number of potential proteomic biomarkers that are related to a number of aspects of SLE have been identified using mass spectrometry proteomic approaches. However, further studies are required to assess the utility of these biomarkers in routine clinical practice. © 2016 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

  18. Improving mass measurement accuracy in mass spectrometry based proteomics by combining open source tools for chromatographic alignment and internal calibration.

    Science.gov (United States)

    Palmblad, Magnus; van der Burgt, Yuri E M; Dalebout, Hans; Derks, Rico J E; Schoenmaker, Bart; Deelder, André M

    2009-05-02

    Accurate mass determination enhances peptide identification in mass spectrometry based proteomics. We here describe the combination of two previously published open source software tools to improve mass measurement accuracy in Fourier transform ion cyclotron resonance mass spectrometry (FTICRMS). The first program, msalign, aligns one MS/MS dataset with one FTICRMS dataset. The second software, recal2, uses peptides identified from the MS/MS data for automated internal calibration of the FTICR spectra, resulting in sub-ppm mass measurement errors.

  19. Mass spectrometry-based metabolomics: applications to biomarker and metabolic pathway research.

    Science.gov (United States)

    Zhang, Aihua; Sun, Hui; Yan, Guangli; Wang, Ping; Wang, Xijun

    2016-01-01

    Mass spectrometry-based metabolomics has become increasingly popular in molecular medicine. High-definition mass spectrometry (MS), coupled with pattern recognition methods, have been carried out to obtain comprehensive metabolite profiling and metabolic pathway of large biological datasets. This sets the scene for a new and powerful diagnostic approach. Analysis of the key metabolites in body fluids has become an important part of improving disease diagnosis. With technological advances in analytical techniques, the ability to measure low-molecular-weight metabolites in bio-samples provides a powerful platform for identifying metabolites that are uniquely correlated with a specific human disease. MS-based metabolomics can lead to enhanced understanding of disease mechanisms and to new diagnostic markers and has a strong potential to contribute to improving early diagnosis of diseases. This review will highlight the importance and benefit with certain characteristic examples of MS-metabolomics for identifying metabolic pathways and metabolites that accurately screen for potential diagnostic biomarkers of diseases. Copyright © 2015 John Wiley & Sons, Ltd.

  20. Advancement of mass spectrometry-based proteomics technologies to explore triple negative breast cancer.

    Science.gov (United States)

    Miah, Sayem; Banks, Charles A S; Adams, Mark K; Florens, Laurence; Lukong, Kiven E; Washburn, Michael P

    2016-12-20

    Understanding the complexity of cancer biology requires extensive information about the cancer proteome over the course of the disease. The recent advances in mass spectrometry-based proteomics technologies have led to the accumulation of an incredible amount of such proteomic information. This information allows us to identify protein signatures or protein biomarkers, which can be used to improve cancer diagnosis, prognosis and treatment. For example, mass spectrometry-based proteomics has been used in breast cancer research for over two decades to elucidate protein function. Breast cancer is a heterogeneous group of diseases with distinct molecular features that are reflected in tumour characteristics and clinical outcomes. Compared with all other subtypes of breast cancer, triple-negative breast cancer is perhaps the most distinct in nature and heterogeneity. In this review, we provide an introductory overview of the application of advanced proteomic technologies to triple-negative breast cancer research.

  1. A new liquid chromatography-mass spectrometry-based method to quantitate exogenous recombinant transferrin in cerebrospinal fluid: a potential approach for pharmacokinetic studies of transferrin-based therapeutics in the central nervous systems.

    Science.gov (United States)

    Wang, Shunhai; Bobst, Cedric E; Kaltashov, Igor A

    2015-01-01

    Transferrin (Tf) is an 80 kDa iron-binding protein that is viewed as a promising drug carrier to target the central nervous system as a result of its ability to penetrate the blood-brain barrier. Among the many challenges during the development of Tf-based therapeutics, the sensitive and accurate quantitation of the administered Tf in cerebrospinal fluid (CSF) remains particularly difficult because of the presence of abundant endogenous Tf. Herein, we describe the development of a new liquid chromatography-mass spectrometry-based method for the sensitive and accurate quantitation of exogenous recombinant human Tf in rat CSF. By taking advantage of a His-tag present in recombinant Tf and applying Ni affinity purification, the exogenous human serum Tf can be greatly enriched from rat CSF, despite the presence of the abundant endogenous protein. Additionally, we applied a newly developed (18)O-labeling technique that can generate internal standards at the protein level, which greatly improved the accuracy and robustness of quantitation. The developed method was investigated for linearity, accuracy, precision, and lower limit of quantitation, all of which met the commonly accepted criteria for bioanalytical method validation.

  2. Comparative Analysis of two Helicobacter pylori Strains using Genomics and Mass Spectrometry-Based Proteomics

    Directory of Open Access Journals (Sweden)

    Roger Karlsson

    2016-11-01

    Full Text Available Helicobacter pylori, a gastroenteric pathogen believed to have co-evolved with humans over 100,000 years, shows significant genetic variability. This motivates the study of different H. pylori strains and the diseases they cause in order to identify determinants for disease evolution. In this study, we used proteomics tools to compare two H. pylori strains. Nic25_A was isolated in Nicaragua from a patient with intestinal metaplasia, and P12 was isolated in Europe from a patient with duodenal ulcers. Differences in the abundance of surface proteins between the two strains were determined with two mass spectrometry-based methods, label-free quantification (MaxQuant or the use of tandem mass tags (TMT. Each approach used a lipid-based protein immobilization (LPI™ technique to enrich peptides of surface proteins. Using the MaxQuant software, we found 52 proteins that differed significantly in abundance between the two strains (up- or downregulated by a factor of 1.5; with TMT, we found 18 proteins that differed in abundance between the strains. Strain P12 had a higher abundance of proteins encoded by the cag pathogenicity island, while levels of the acid response regulator ArsR and its regulatory targets (KatA, AmiE, and proteins involved in urease production were higher in strain Nic25_A. Our results show that differences in protein abundance between H. pylori strains can be detected with proteomic approaches; this could have important implications for the study of disease progression.

  3. Mass spectrometry-based metabolomics: Targeting the crosstalk between gut microbiota and brain in neurodegenerative disorders.

    Science.gov (United States)

    Luan, Hemi; Wang, Xian; Cai, Zongwei

    2017-11-12

    Metabolomics seeks to take a "snapshot" in a time of the levels, activities, regulation and interactions of all small molecule metabolites in response to a biological system with genetic or environmental changes. The emerging development in mass spectrometry technologies has shown promise in the discovery and quantitation of neuroactive small molecule metabolites associated with gut microbiota and brain. Significant progress has been made recently in the characterization of intermediate role of small molecule metabolites linked to neural development and neurodegenerative disorder, showing its potential in understanding the crosstalk between gut microbiota and the host brain. More evidence reveals that small molecule metabolites may play a critical role in mediating microbial effects on neurotransmission and disease development. Mass spectrometry-based metabolomics is uniquely suitable for obtaining the metabolic signals in bidirectional communication between gut microbiota and brain. In this review, we summarized major mass spectrometry technologies including liquid chromatography-mass spectrometry, gas chromatography-mass spectrometry, and imaging mass spectrometry for metabolomics studies of neurodegenerative disorders. We also reviewed the recent advances in the identification of new metabolites by mass spectrometry and metabolic pathways involved in the connection of intestinal microbiota and brain. These metabolic pathways allowed the microbiota to impact the regular function of the brain, which can in turn affect the composition of microbiota via the neurotransmitter substances. The dysfunctional interaction of this crosstalk connects neurodegenerative diseases, including Parkinson's disease, Alzheimer's disease and Huntington's disease. The mass spectrometry-based metabolomics analysis provides information for targeting dysfunctional pathways of small molecule metabolites in the development of the neurodegenerative diseases, which may be valuable for the

  4. Catch and measure-mass spectrometry-based immunoassays in biomarker research.

    Science.gov (United States)

    Weiß, Frederik; van den Berg, Bart H J; Planatscher, Hannes; Pynn, Christopher J; Joos, Thomas O; Poetz, Oliver

    2014-05-01

    Mass spectrometry-based (MS) methods are effective tools for discovering protein biomarker candidates that can differentiate between physiological and pathophysiological states. Promising candidates are validated in studies comprising large patient cohorts. Here, targeted protein analytics are used to increase sample throughput. Methods involving antibodies, such as sandwich immunoassays or Western blots, are commonly applied at this stage. Highly-specific and sensitive mass spectrometry-based immunoassays that have been established in recent years offer a suitable alternative to sandwich immunoassays for quantifying proteins. Mass Spectrometric ImmunoAssays (MSIA) and Stable Isotope Standards and Capture by Anti-Peptide Antibodies (SISCAPA/iMALDI) are two prominent types of MS-based immunoassays in which the capture is done either at the protein or the peptide level. We present an overview of these emerging types of immunoassays and discuss their suitability for the discovery and validation of protein biomarkers. This article is part of a Special Issue entitled: Biomarkers: A Proteomic Challenge. © 2013.

  5. The Role of Mass Spectrometry-Based Metabolomics in Medical Countermeasures Against Radiation

    Science.gov (United States)

    Patterson, Andrew D.; Lanz, Christian; Gonzalez, Frank J.; Idle, Jeffrey R.

    2013-01-01

    Radiation metabolomics can be defined as the global profiling of biological fluids to uncover latent, endogenous small molecules whose concentrations change in a dose-response manner following exposure to ionizing radiation. In response to the potential threat of nuclear or radiological terrorism, the Center for High-Throughput Minimally Invasive Radiation Biodosimetry (CMCR) was established to develop field-deployable biodosimeters based, in principle, on rapid analysis by mass spectrometry of readily and easily obtainable biofluids. In this review, we briefly summarize radiation biology and key events related to actual and potential nuclear disasters, discuss the important contributions the field of mass spectrometry has made to the field of radiation metabolomics, and summarize current discovery efforts to use mass spectrometry-based metabolomics to identify dose-responsive urinary constituents, and ultimately to build and deploy a noninvasive high-throughput biodosimeter. PMID:19890938

  6. A guide through the computational analysis of isotope-labeled mass spectrometry-based quantitative proteomics data: an application study

    Directory of Open Access Journals (Sweden)

    Haußmann Ute

    2011-06-01

    Full Text Available Abstract Background Mass spectrometry-based proteomics has reached a stage where it is possible to comprehensively analyze the whole proteome of a cell in one experiment. Here, the employment of stable isotopes has become a standard technique to yield relative abundance values of proteins. In recent times, more and more experiments are conducted that depict not only a static image of the up- or down-regulated proteins at a distinct time point but instead compare developmental stages of an organism or varying experimental conditions. Results Although the scientific questions behind these experiments are of course manifold, there are, nevertheless, two questions that commonly arise: 1 which proteins are differentially regulated regarding the selected experimental conditions, and 2 are there groups of proteins that show similar abundance ratios, indicating that they have a similar turnover? We give advice on how these two questions can be answered and comprehensively compare a variety of commonly applied computational methods and their outcomes. Conclusions This work provides guidance through the jungle of computational methods to analyze mass spectrometry-based isotope-labeled datasets and recommends an effective and easy-to-use evaluation strategy. We demonstrate our approach with three recently published datasets on Bacillus subtilis 12 and Corynebacterium glutamicum 3. Special focus is placed on the application and validation of cluster analysis methods. All applied methods were implemented within the rich internet application QuPE 4. Results can be found at http://qupe.cebitec.uni-bielefeld.de.

  7. Web-based resources for mass-spectrometry-based metabolomics: a user's guide.

    Science.gov (United States)

    Tohge, Takayuki; Fernie, Alisdair R

    2009-03-01

    In recent years, a plethora of web-based tools aimed at supporting mass-spectrometry-based metabolite profiling and metabolomics applications have appeared. Given the huge hurdles presented by the chemical diversity and dynamic range of the metabolites present in the plant kingdom, profiling the levels of a broad range of metabolites is highly challenging. Given the scale and costs involved in defining the plant metabolome, it is imperative that data are effectively shared between laboratories pursuing this goal. However, ensuring accurate comparison of samples run on the same machine within the same laboratory, let alone cross-machine and cross-laboratory comparisons, requires both careful experimentation and data interpretation. In this review, we present an overview of currently available software that aids either in peak identification or in the related field of peak alignment as well as those with utility in defining structural information of compounds and metabolic pathways.

  8. Mass Spectrometry-Based Proteomics for Pre-Eclampsia and Preterm Birth

    Science.gov (United States)

    Law, Kai P.; Han, Ting-Li; Tong, Chao; Baker, Philip N.

    2015-01-01

    Pregnancy-related complications such as pre-eclampsia and preterm birth now represent a notable burden of adverse health. Pre-eclampsia is a hypertensive disorder unique to pregnancy. It is an important cause of maternal death worldwide and a leading cause of fetal growth restriction and iatrogenic prematurity. Fifteen million infants are born preterm each year globally, but more than one million of those do not survive their first month of life. Currently there are no predictive tests available for diagnosis of these pregnancy-related complications and the biological mechanisms of the diseases have not been fully elucidated. Mass spectrometry-based proteomics have all the necessary attributes to provide the needed breakthrough in understanding the pathophysiology of complex human diseases thorough the discovery of biomarkers. The mass spectrometry methodologies employed in the studies for pregnancy-related complications are evaluated in this article. Top-down proteomic and peptidomic profiling by laser mass spectrometry, liquid chromatography or capillary electrophoresis coupled to mass spectrometry, and bottom-up quantitative proteomics and targeted proteomics by liquid chromatography mass spectrometry have been applied to elucidate protein biomarkers and biological mechanism of pregnancy-related complications. The proteomes of serum, urine, amniotic fluid, cervical-vaginal fluid, placental tissue, and cytotrophoblastic cells have all been investigated. Numerous biomarkers or biomarker candidates that could distinguish complicated pregnancies from healthy controls have been proposed. Nevertheless, questions as to the clinically utility and the capacity to elucidate the pathogenesis of the pre-eclampsia and preterm birth remain to be answered. PMID:26006232

  9. Mass Spectrometry-Based Proteomics for Pre-Eclampsia and Preterm Birth

    Directory of Open Access Journals (Sweden)

    Kai P. Law

    2015-05-01

    Full Text Available Pregnancy-related complications such as pre-eclampsia and preterm birth now represent a notable burden of adverse health. Pre-eclampsia is a hypertensive disorder unique to pregnancy. It is an important cause of maternal death worldwide and a leading cause of fetal growth restriction and iatrogenic prematurity. Fifteen million infants are born preterm each year globally, but more than one million of those do not survive their first month of life. Currently there are no predictive tests available for diagnosis of these pregnancy-related complications and the biological mechanisms of the diseases have not been fully elucidated. Mass spectrometry-based proteomics have all the necessary attributes to provide the needed breakthrough in understanding the pathophysiology of complex human diseases thorough the discovery of biomarkers. The mass spectrometry methodologies employed in the studies for pregnancy-related complications are evaluated in this article. Top-down proteomic and peptidomic profiling by laser mass spectrometry, liquid chromatography or capillary electrophoresis coupled to mass spectrometry, and bottom-up quantitative proteomics and targeted proteomics by liquid chromatography mass spectrometry have been applied to elucidate protein biomarkers and biological mechanism of pregnancy-related complications. The proteomes of serum, urine, amniotic fluid, cervical-vaginal fluid, placental tissue, and cytotrophoblastic cells have all been investigated. Numerous biomarkers or biomarker candidates that could distinguish complicated pregnancies from healthy controls have been proposed. Nevertheless, questions as to the clinically utility and the capacity to elucidate the pathogenesis of the pre-eclampsia and preterm birth remain to be answered.

  10. YPED: an integrated bioinformatics suite and database for mass spectrometry-based proteomics research.

    Science.gov (United States)

    Colangelo, Christopher M; Shifman, Mark; Cheung, Kei-Hoi; Stone, Kathryn L; Carriero, Nicholas J; Gulcicek, Erol E; Lam, TuKiet T; Wu, Terence; Bjornson, Robert D; Bruce, Can; Nairn, Angus C; Rinehart, Jesse; Miller, Perry L; Williams, Kenneth R

    2015-02-01

    We report a significantly-enhanced bioinformatics suite and database for proteomics research called Yale Protein Expression Database (YPED) that is used by investigators at more than 300 institutions worldwide. YPED meets the data management, archival, and analysis needs of a high-throughput mass spectrometry-based proteomics research ranging from a single laboratory, group of laboratories within and beyond an institution, to the entire proteomics community. The current version is a significant improvement over the first version in that it contains new modules for liquid chromatography-tandem mass spectrometry (LC-MS/MS) database search results, label and label-free quantitative proteomic analysis, and several scoring outputs for phosphopeptide site localization. In addition, we have added both peptide and protein comparative analysis tools to enable pairwise analysis of distinct peptides/proteins in each sample and of overlapping peptides/proteins between all samples in multiple datasets. We have also implemented a targeted proteomics module for automated multiple reaction monitoring (MRM)/selective reaction monitoring (SRM) assay development. We have linked YPED's database search results and both label-based and label-free fold-change analysis to the Skyline Panorama repository for online spectra visualization. In addition, we have built enhanced functionality to curate peptide identifications into an MS/MS peptide spectral library for all of our protein database search identification results. Copyright © 2015 The Authors. Production and hosting by Elsevier Ltd.. All rights reserved.

  11. Mass Spectrometry-Based Proteomics for the Analysis of Chromatin Structure and Dynamics

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    Monica Soldi

    2013-03-01

    Full Text Available Chromatin is a highly structured nucleoprotein complex made of histone proteins and DNA that controls nearly all DNA-dependent processes. Chromatin plasticity is regulated by different associated proteins, post-translational modifications on histones (hPTMs and DNA methylation, which act in a concerted manner to enforce a specific “chromatin landscape”, with a regulatory effect on gene expression. Mass Spectrometry (MS has emerged as a powerful analytical strategy to detect histone PTMs, revealing interplays between neighbouring PTMs and enabling screens for their readers in a comprehensive and quantitative fashion. Here we provide an overview of the recent achievements of state-of-the-art mass spectrometry-based proteomics for the detailed qualitative and quantitative characterization of histone post-translational modifications, histone variants, and global interactomes at specific chromatin regions. This synopsis emphasizes how the advances in high resolution MS, from “Bottom Up” to “Top Down” analysis, together with the uptake of quantitative proteomics methods by chromatin biologists, have made MS a well-established method in the epigenetics field, enabling the acquisition of original information, highly complementary to that offered by more conventional, antibody-based, assays.

  12. A versatile mass spectrometry-based method to both identify kinase client-relationships and characterize signaling network topology

    Science.gov (United States)

    While more than a thousand protein kinases (PK) have been identified in the Arabidopsis thaliana genome, relatively little progress has been made towards identifying their individual client proteins. Herein we describe use of a mass spectrometry-based in vitro phosphorylation strategy, termed Kinase...

  13. Ultra-high performance liquid chromatography coupled with quadrupole/time of flight mass spectrometry based chemical profiling approach for the holistic quality control of complex Kang-Jing formula preparations.

    Science.gov (United States)

    Yang, Xiao-Huan; Cheng, Xiao-Lan; Qin, Bing; Cai, Zhuo-Ya; Cai, Xiong; Liu, Shao; Wang, Qi; Qin, Yong

    2016-05-30

    The Kang-Jing (KJ) formula is a compound preparation made from 12 kinds of herbs. So far, four different methods (M1-M4) have been documented for KJ preparation, but the influence of preparation methods on the holistic quality of KJ have remained unknown. In this study, a strategy was proposed to investigate the influence of different preparation methods on the holistic quality of KJ using ultra-high performance liquid chromatography coupled with quadrupole/time of flight mass spectrometry (UHPLC-QTOF-MS/MS) based chemical profiling. A total of 101 compounds mainly belonging to flavonoids, tanshinones, monoterpene glycosides, triterpenoid saponins, alkaloids, phenolic acids and volatile oils, were identified. Among these compounds, glaucine was detected only in M3/M4 samples, while two dehydrocorydaline isomers merely detected in M2/M3/M4 samples. Tetrahydrocolumbamine, ethylic lithospermic acid, salvianolic acid E and rosmarimic acid were only detected in M1/M3/M4 samples. In the subsequent quantitative analysis, 12 major compounds were determined by UHPLC-MS/MS. The proposed method was validated with respect to linearity, accuracy, precision and recovery. It was found that the contents of marker compounds varied significantly in samples prepared by different methods. These results demonstrated that preparation method does significantly affect the holistic quality of KJ. UHPLC-QTOF-MS/MS based chemical profiling approach is efficient and reliable for comprehensive quality evaluation of KJ. Collectively, this study provide the chemical evidence for revealing the material basis of KJ, and establish a simple and accurate chemical profiling method for its quality control. Copyright © 2016 Elsevier B.V. All rights reserved.

  14. A mass spectrometry-based assay for improved quantitative measurements of efflux pump inhibition.

    Directory of Open Access Journals (Sweden)

    Adam R Brown

    Full Text Available Bacterial efflux pumps are active transport proteins responsible for resistance to selected biocides and antibiotics. It has been shown that production of efflux pumps is up-regulated in a number of highly pathogenic bacteria, including methicillin resistant Staphylococcus aureus. Thus, the identification of new bacterial efflux pump inhibitors is a topic of great interest. Existing assays to evaluate efflux pump inhibitory activity rely on fluorescence by an efflux pump substrate. When employing these assays to evaluate efflux pump inhibitory activity of plant extracts and some purified compounds, we observed severe optical interference that gave rise to false negative results. To circumvent this problem, a new mass spectrometry-based method was developed for the quantitative measurement of bacterial efflux pump inhibition. The assay was employed to evaluate efflux pump inhibitory activity of a crude extract of the botanical Hydrastis Canadensis, and to compare the efflux pump inhibitory activity of several pure flavonoids. The flavonoid quercetin, which appeared to be completely inactive with a fluorescence-based method, showed an IC50 value of 75 μg/mL with the new method. The other flavonoids evaluated (apigenin, kaempferol, rhamnetin, luteolin, myricetin, were also active, with IC50 values ranging from 19 μg/mL to 75 μg/mL. The assay described herein could be useful in future screening efforts to identify efflux pump inhibitors, particularly in situations where optical interference precludes the application of methods that rely on fluorescence.

  15. Mass Spectrometry-Based Quantitative Metabolomics Revealed a Distinct Lipid Profile in Breast Cancer Patients

    Directory of Open Access Journals (Sweden)

    Yun Yen

    2013-04-01

    Full Text Available Breast cancer accounts for the largest number of newly diagnosed cases in female cancer patients. Although mammography is a powerful screening tool, about 20% of breast cancer cases cannot be detected by this method. New diagnostic biomarkers for breast cancer are necessary. Here, we used a mass spectrometry-based quantitative metabolomics method to analyze plasma samples from 55 breast cancer patients and 25 healthy controls. A number of 30 patients and 20 age-matched healthy controls were used as a training dataset to establish a diagnostic model and to identify potential biomarkers. The remaining samples were used as a validation dataset to evaluate the predictive accuracy for the established model. Distinct separation was obtained from an orthogonal partial least squares-discriminant analysis (OPLS-DA model with good prediction accuracy. Based on this analysis, 39 differentiating metabolites were identified, including significantly lower levels of lysophosphatidylcholines and higher levels of sphingomyelins in the plasma samples obtained from breast cancer patients compared with healthy controls. Using logical regression, a diagnostic equation based on three metabolites (lysoPC a C16:0, PC ae C42:5 and PC aa C34:2 successfully differentiated breast cancer patients from healthy controls, with a sensitivity of 98.1% and a specificity of 96.0%.

  16. A Mass Spectrometry-Based Predictive Strategy Reveals ADAP1 is Phosphorylated at Tyrosine 364

    Energy Technology Data Exchange (ETDEWEB)

    Littrell, BobbiJo R [National Renewable Energy Laboratory (NREL), Golden, CO (United States)

    2018-04-16

    The goal of this work was to identify phosphorylation sites within the amino acid sequence of human ADAP1. Using traditional mass spectrometry-based techniques we were unable to produce interpretable spectra demonstrating modification by phosphorylation. This prompted us to employ a strategy in which phosphorylated peptides were first predicted using peptide mapping followed by targeted MS/MS acquisition. ADAP1 was immunoprecipitated from extracts of HEK293 cells stably-transfected with ADAP1 cDNA. Immunoprecipitated ADAP1 was digested with proteolytic enzymes and analyzed by LC-MS in MS1 mode by high-resolution quadrupole time-of-flight mass spectrometry (QTOF-MS). Peptide molecular features were extracted using an untargeted data mining algorithm. Extracted peptide neutral masses were matched against the ADAP1 amino acid sequence with phosphorylation included as a predicted modification. Peptides with predicted phosphorylation sites were analyzed by targeted LC-MS2. Acquired MS2 spectra were then analyzed using database search engines to confirm phosphorylation. Spectra of phosphorylated peptides were validated by manual interpretation. Further confirmation was performed by manipulating phospho-peptide abundance using calf intestinal phosphatase (CIP) and the phorbol ester, phorbol 12-myristate 13-acetate (PMA). Of five predicted phosphopeptides, one, comprised of the sequence AVDRPMLPQEYAVEAHFK, was confirmed to be phosphorylated on a Tyrosine at position 364. Pre-treatment of cells with PMA prior to immunoprecipitation increased the ratio of phosphorylated to unphosphorylated peptide as determined by area counts of extracted ion chromatograms (EIC). Addition of CIP to immunoprecipitation reactions eliminated the phosphorylated form. A novel phosphorylation site was identified at Tyrosine 364. Phosphorylation at this site is increased by treatment with PMA. PMA promotes membrane translocation and activation of protein kinase C (PKC), indicating that Tyrosine 364

  17. An integrated strategy for in vivo metabolite profiling using high-resolution mass spectrometry based data processing techniques

    International Nuclear Information System (INIS)

    Guo, Jian; Zhang, Minli; Elmore, Charles S.; Vishwanathan, Karthick

    2013-01-01

    Graphical abstract: -- Highlights: •Profiling the metabolites of model compounds in rats using high resolution mass spectrometry based data processing techniques. •Demonstrating an integrated strategy in vivo metabolite profiling using data mining tools. •Unusual metabolites generated via thiazole-ring opening were characterized based on processed LC–MS.data. -- Abstract: An ongoing challenge of drug metabolite profiling is to detect and identify unknown or low-level metabolites in complex biological matrices. Here we present a generic strategy for metabolite detection using multiple accurate-mass-based data processing tools via the analysis of rat samples of two model drug candidates, AZD6280 and AZ12488024. First, the function of isotopic pattern recognition was proved to be highly effective in the detection of metabolites derived from [ 14 C]-AZD6280 that possesses a distinct isotopic pattern. The metabolites revealed using this approach were in excellent qualitative correlation to those observed in radiochromatograms. Second, the effectiveness of accurate mass based untargeted data mining tools such as background subtraction, mass defect filtering, or a data mining package (MZmine) used for metabolomic analysis in detection of metabolites of [ 14 C]-AZ12488024 in rat urine, feces, bile and plasma samples was examined and a total of 33 metabolites of AZ12488024 were detected. Among them, at least 16 metabolites were only detected by the aid of the data mining packages and not via radiochromatograms. New metabolic pathways such as S-oxidation and thiomethylation reactions occurring on the thiazole ring were proposed based on the processed data. The results of these experiments also demonstrated that accurate mass-based mass defect filtering (MDF) and data mining techniques used in metabolomics are complementary and can be valuable tools for delineating low-level metabolites in complex matrices. Furthermore, the application of distinct multiple data

  18. Conventional and Advanced Separations in Mass Spectrometry-Based Metabolomics: Methodologies and Applications

    Energy Technology Data Exchange (ETDEWEB)

    Heyman, Heino M.; Zhang, Xing; Tang, Keqi; Baker, Erin Shammel; Metz, Thomas O.

    2016-02-16

    Metabolomics is the quantitative analysis of all metabolites in a given sample. Due to the chemical complexity of the metabolome, optimal separations are required for comprehensive identification and quantification of sample constituents. This chapter provides an overview of both conventional and advanced separations methods in practice for reducing the complexity of metabolite extracts delivered to the mass spectrometer detector, and covers gas chromatography (GC), liquid chromatography (LC), capillary electrophoresis (CE), supercritical fluid chromatography (SFC) and ion mobility spectrometry (IMS) separation techniques coupled with mass spectrometry (MS) as both uni-dimensional and as multi-dimensional approaches.

  19. The application of mass-spectrometry-based protein biomarker discovery to theragnostics

    OpenAIRE

    Street, Jonathan M; Dear, James W

    2010-01-01

    Over the last decade rapid developments in mass spectrometry have allowed the identification of multiple proteins in complex biological samples. This proteomic approach has been applied to biomarker discovery in the context of clinical pharmacology (the combination of biomarker and drug now being termed ‘theragnostics’). In this review we provide a roadmap for early protein biomarker discovery studies, focusing on some key questions that regularly confront researchers.

  20. MALDI mass spectrometry based molecular phenotyping of CNS glial cells for prediction in mammalian brain tissue

    DEFF Research Database (Denmark)

    Hanrieder, Jørg; Wicher, Grzegorz; Bergquist, Jonas

    2011-01-01

    . Complementary proteomic experiments revealed the identity of these signature proteins that were predominantly expressed in the different glial cell types, including histone H4 for oligodendrocytes and S100-A10 for astrocytes. MALDI imaging MS was performed, and signature masses were employed as molecular...... tracers for prediction of oligodendroglial and astroglial localization in brain tissue. The different cell type specific protein distributions in tissue were validated using immunohistochemistry. ICMS of intact neuroglia is a simple and straightforward approach for characterization and discrimination...

  1. Discovery and characterization of antibody variants using mass spectrometry-based comparative analysis for biosimilar candidates of monoclonal antibody drugs.

    Science.gov (United States)

    Li, Wenhua; Yang, Bin; Zhou, Dongmei; Xu, Jun; Ke, Zhi; Suen, Wen-Chen

    2016-07-01

    Liquid chromatography mass spectrometry (LC-MS) is the most commonly used technique for the characterization of antibody variants. MAb-X and mAb-Y are two approved IgG1 subtype monoclonal antibody drugs recombinantly produced in Chinese hamster ovary (CHO) cells. We report here that two unexpected and rare antibody variants have been discovered during cell culture process development of biosimilars for these two approved drugs through intact mass analysis. We then used comprehensive mass spectrometry-based comparative analysis including reduced light, heavy chains, and domain-specific mass as well as peptide mapping analysis to fully characterize the observed antibody variants. The "middle-up" mass comparative analysis demonstrated that the antibody variant from mAb-X biosimilar candidate was caused by mass variation of antibody crystalline fragment (Fc), whereas a different variant with mass variation in antibody antigen-binding fragment (Fab) from mAb-Y biosimilar candidate was identified. Endoproteinase Lys-C digested peptide mapping and tandem mass spectrometry analysis further revealed that a leucine to glutamine change in N-terminal 402 site of heavy chain was responsible for the generation of mAb-X antibody variant. Lys-C and trypsin coupled non-reduced and reduced peptide mapping comparative analysis showed that the formation of the light-heavy interchain trisulfide bond resulted in the mAb-Y antibody variant. These two cases confirmed that mass spectrometry-based comparative analysis plays a critical role for the characterization of monoclonal antibody variants, and biosimilar developers should start with a comprehensive structural assessment and comparative analysis to decrease the risk of the process development for biosimilars. Copyright © 2016 Elsevier B.V. All rights reserved.

  2. Mass Spectrometry-Based Methods for Identifying Oxidized Proteins in Disease: Advances and Challenges

    Directory of Open Access Journals (Sweden)

    Ivan Verrastro

    2015-04-01

    Full Text Available Many inflammatory diseases have an oxidative aetiology, which leads to oxidative damage to biomolecules, including proteins. It is now increasingly recognized that oxidative post-translational modifications (oxPTMs of proteins affect cell signalling and behaviour, and can contribute to pathology. Moreover, oxidized proteins have potential as biomarkers for inflammatory diseases. Although many assays for generic protein oxidation and breakdown products of protein oxidation are available, only advanced tandem mass spectrometry approaches have the power to localize specific oxPTMs in identified proteins. While much work has been carried out using untargeted or discovery mass spectrometry approaches, identification of oxPTMs in disease has benefitted from the development of sophisticated targeted or semi-targeted scanning routines, combined with chemical labeling and enrichment approaches. Nevertheless, many potential pitfalls exist which can result in incorrect identifications. This review explains the limitations, advantages and challenges of all of these approaches to detecting oxidatively modified proteins, and provides an update on recent literature in which they have been used to detect and quantify protein oxidation in disease.

  3. Clinical diagnosis and typing of systemic amyloidosis in subcutaneous fat aspirates by mass spectrometry-based proteomics.

    Science.gov (United States)

    Vrana, Julie A; Theis, Jason D; Dasari, Surendra; Mereuta, Oana M; Dispenzieri, Angela; Zeldenrust, Steven R; Gertz, Morie A; Kurtin, Paul J; Grogg, Karen L; Dogan, Ahmet

    2014-07-01

    Examination of abdominal subcutaneous fat aspirates is a practical, sensitive and specific method for the diagnosis of systemic amyloidosis. Here we describe the development and implementation of a clinical assay using mass spectrometry-based proteomics to type amyloidosis in subcutaneous fat aspirates. First, we validated the assay comparing amyloid-positive (n=43) and -negative (n=26) subcutaneous fat aspirates. The assay classified amyloidosis with 88% sensitivity and 96% specificity. We then implemented the assay as a clinical test, and analyzed 366 amyloid-positive subcutaneous fat aspirates in a 4-year period as part of routine clinical care. The assay had a sensitivity of 90%, and diverse amyloid types, including immunoglobulin light chain (74%), transthyretin (13%), serum amyloid A (%1), gelsolin (1%), and lysozyme (1%), were identified. Using bioinformatics, we identified a universal amyloid proteome signature, which has high sensitivity and specificity for amyloidosis similar to that of Congo red staining. We curated proteome databases which included variant proteins associated with systemic amyloidosis, and identified clonotypic immunoglobulin variable gene usage in immunoglobulin light chain amyloidosis, and the variant peptides in hereditary transthyretin amyloidosis. In conclusion, mass spectrometry-based proteomic analysis of subcutaneous fat aspirates offers a powerful tool for the diagnosis and typing of systemic amyloidosis. The assay reveals the underlying pathogenesis by identifying variable gene usage in immunoglobulin light chains and the variant peptides in hereditary amyloidosis. Copyright© Ferrata Storti Foundation.

  4. Advances in high-resolution mass spectrometry based on metabolomics studies for food--a review.

    Science.gov (United States)

    Rubert, Josep; Zachariasova, Milena; Hajslova, Jana

    2015-01-01

    Food authenticity becomes a necessity for global food policies, since food placed in the market without fail has to be authentic. It has always been a challenge, since in the past minor components, called also markers, have been mainly monitored by chromatographic methods in order to authenticate the food. Nevertheless, nowadays, advanced analytical methods have allowed food fingerprints to be achieved. At the same time they have been also combined with chemometrics, which uses statistical methods in order to verify food and to provide maximum information by analysing chemical data. These sophisticated methods based on different separation techniques or stand alone have been recently coupled to high-resolution mass spectrometry (HRMS) in order to verify the authenticity of food. The new generation of HRMS detectors have experienced significant advances in resolving power, sensitivity, robustness, extended dynamic range, easier mass calibration and tandem mass capabilities, making HRMS more attractive and useful to the food metabolomics community, therefore becoming a reliable tool for food authenticity. The purpose of this review is to summarise and describe the most recent metabolomics approaches in the area of food metabolomics, and to discuss the strengths and drawbacks of the HRMS analytical platforms combined with chemometrics.

  5. Mass spectrometry-based serum proteome pattern analysis in molecular diagnostics of early stage breast cancer

    Directory of Open Access Journals (Sweden)

    Stobiecki Maciej

    2009-07-01

    Full Text Available Abstract Background Mass spectrometric analysis of the blood proteome is an emerging method of clinical proteomics. The approach exploiting multi-protein/peptide sets (fingerprints detected by mass spectrometry that reflect overall features of a specimen's proteome, termed proteome pattern analysis, have been already shown in several studies to have applicability in cancer diagnostics. We aimed to identify serum proteome patterns specific for early stage breast cancer patients using MALDI-ToF mass spectrometry. Methods Blood samples were collected before the start of therapy in a group of 92 patients diagnosed at stages I and II of the disease, and in a group of age-matched healthy controls (104 women. Serum specimens were purified and the low-molecular-weight proteome fraction was examined using MALDI-ToF mass spectrometry after removal of albumin and other high-molecular-weight serum proteins. Protein ions registered in a mass range between 2,000 and 10,000 Da were analyzed using a new bioinformatic tool created in our group, which included modeling spectra as a sum of Gaussian bell-shaped curves. Results We have identified features of serum proteome patterns that were significantly different between blood samples of healthy individuals and early stage breast cancer patients. The classifier built of three spectral components that differentiated controls and cancer patients had 83% sensitivity and 85% specificity. Spectral components (i.e., protein ions that were the most frequent in such classifiers had approximate m/z values of 2303, 2866 and 3579 Da (a biomarker built from these three components showed 88% sensitivity and 78% specificity. Of note, we did not find a significant correlation between features of serum proteome patterns and established prognostic or predictive factors like tumor size, nodal involvement, histopathological grade, estrogen and progesterone receptor expression. In addition, we observed a significantly (p = 0

  6. Mass spectrometry-based proteomics: basic principles and emerging technologies and directions.

    Science.gov (United States)

    Van Riper, Susan K; de Jong, Ebbing P; Carlis, John V; Griffin, Timothy J

    2013-01-01

    As the main catalytic and structural molecules within living systems, proteins are the most likely biomolecules to be affected by radiation exposure. Proteomics, the comprehensive characterization of proteins within complex biological samples, is therefore a research approach ideally suited to assess the effects of radiation exposure on cells and tissues. For comprehensive characterization of proteomes, an analytical platform capable of quantifying protein abundance, identifying post-translation modifications and revealing members of protein complexes on a system-wide level is necessary. Mass spectrometry (MS), coupled with technologies for sample fractionation and automated data analysis, provides such a versatile and powerful platform. In this chapter we offer a view on the current state of MS-proteomics, and focus on emerging technologies within three areas: (1) New instrumental methods; (2) New computational methods for peptide identification; and (3) Label-free quantification. These emerging technologies should be valuable for researchers seeking to better understand biological effects of radiation on living systems.

  7. Mass Spectrometry Based Proteomic Analysis of Salivary Glands of Urban Malaria Vector Anopheles stephensi

    Directory of Open Access Journals (Sweden)

    Sonam Vijay

    2014-01-01

    Full Text Available Salivary gland proteins of Anopheles mosquitoes offer attractive targets to understand interactions with sporozoites, blood feeding behavior, homeostasis, and immunological evaluation of malaria vectors and parasite interactions. To date limited studies have been carried out to elucidate salivary proteins of An. stephensi salivary glands. The aim of the present study was to provide detailed analytical attributives of functional salivary gland proteins of urban malaria vector An. stephensi. A proteomic approach combining one-dimensional electrophoresis (1DE, ion trap liquid chromatography mass spectrometry (LC/MS/MS, and computational bioinformatic analysis was adopted to provide the first direct insight into identification and functional characterization of known salivary proteins and novel salivary proteins of An. stephensi. Computational studies by online servers, namely, MASCOT and OMSSA algorithms, identified a total of 36 known salivary proteins and 123 novel proteins analysed by LC/MS/MS. This first report describes a baseline proteomic catalogue of 159 salivary proteins belonging to various categories of signal transduction, regulation of blood coagulation cascade, and various immune and energy pathways of An. stephensi sialotranscriptome by mass spectrometry. Our results may serve as basis to provide a putative functional role of proteins in concept of blood feeding, biting behavior, and other aspects of vector-parasite host interactions for parasite development in anopheline mosquitoes.

  8. Recent mass spectrometry-based proteomics for biomarker discovery in lung cancer, COPD, and asthma.

    Science.gov (United States)

    Fujii, Kiyonaga; Nakamura, Haruhiko; Nishimura, Toshihide

    2017-04-01

    Lung cancer and related diseases have been one of the most common causes of deaths worldwide. Genomic-based biomarkers may hardly reflect the underlying dynamic molecular mechanism of functional protein interactions, which is the center of a disease. Recent developments in mass spectrometry (MS) have made it possible to analyze disease-relevant proteins expressed in clinical specimens by proteomic challenges. Areas covered: To understand the molecular mechanisms of lung cancer and its subtypes, chronic obstructive pulmonary disease (COPD), asthma and others, great efforts have been taken to identify numerous relevant proteins by MS-based clinical proteomic approaches. Since lung cancer is a multifactorial disease that is biologically associated with asthma and COPD among various lung diseases, this study focused on proteomic studies on biomarker discovery using various clinical specimens for lung cancer, COPD, and asthma. Expert commentary: MS-based exploratory proteomics utilizing clinical specimens, which can incorporate both experimental and bioinformatic analysis of protein-protein interaction and also can adopt proteogenomic approaches, makes it possible to reveal molecular networks that are relevant to a disease subgroup and that could differentiate between drug responders and non-responders, good and poor prognoses, drug resistance, and so on.

  9. Global mass spectrometry based metabolomics profiling of erythrocytes infected with Plasmodium falciparum.

    Directory of Open Access Journals (Sweden)

    Theodore R Sana

    Full Text Available Malaria is a global infectious disease that threatens the lives of millions of people. Transcriptomics, proteomics and functional genomics studies, as well as sequencing of the Plasmodium falciparum and Homo sapiens genomes, have shed new light on this host-parasite relationship. Recent advances in accurate mass measurement mass spectrometry, sophisticated data analysis software, and availability of biological pathway databases, have converged to facilitate our global, untargeted biochemical profiling study of in vitro P. falciparum-infected (IRBC and uninfected (NRBC erythrocytes. In order to expand the number of detectable metabolites, several key analytical steps in our workflows were optimized. Untargeted and targeted data mining resulted in detection of over one thousand features or chemical entities. Untargeted features were annotated via matching to the METLIN metabolite database. For targeted data mining, we queried the data using a compound database derived from a metabolic reconstruction of the P. falciparum genome. In total, over one hundred and fifty differential annotated metabolites were observed. To corroborate the representation of known biochemical pathways from our data, an inferential pathway analysis strategy was used to map annotated metabolites onto the BioCyc pathway collection. This hypothesis-generating approach resulted in over-representation of many metabolites onto several IRBC pathways, most prominently glycolysis. In addition, components of the "branched" TCA cycle, partial urea cycle, and nucleotide, amino acid, chorismate, sphingolipid and fatty acid metabolism were found to be altered in IRBCs. Interestingly, we detected and confirmed elevated levels for cyclic ADP ribose and phosphoribosyl AMP in IRBCs, a novel observation. These metabolites may play a role in regulating the release of intracellular Ca(2+ during P. falciparum infection. Our results support a strategy of global metabolite profiling by untargeted

  10. Ranked solutions to a class of combinatorial optimizations - with applications in mass spectrometry based peptide sequencing

    Science.gov (United States)

    Doerr, Timothy; Alves, Gelio; Yu, Yi-Kuo

    2006-03-01

    Typical combinatorial optimizations are NP-hard; however, for a particular class of cost functions the corresponding combinatorial optimizations can be solved in polynomial time. This suggests a way to efficiently find approximate solutions - - find a transformation that makes the cost function as similar as possible to that of the solvable class. After keeping many high-ranking solutions using the approximate cost function, one may then re-assess these solutions with the full cost function to find the best approximate solution. Under this approach, it is important to be able to assess the quality of the solutions obtained, e.g., by finding the true ranking of kth best approximate solution when all possible solutions are considered exhaustively. To tackle this statistical issue, we provide a systematic method starting with a scaling function generated from the fininte number of high- ranking solutions followed by a convergent iterative mapping. This method, useful in a variant of the directed paths in random media problem proposed here, can also provide a statistical significance assessment for one of the most important proteomic tasks - - peptide sequencing using tandem mass spectrometry data.

  11. Purification and mass spectrometry based characterization of a pediocin produced by Pediococcus acidilactici 13.

    Science.gov (United States)

    Altuntaş, Evrim Güneş; Ayhan, Kamuran; Peker, Selen; Ayhan, Beycan; Demiralp, Duygu Ozel

    2014-10-01

    Bacteriocins are antimicrobial peptides produced by several bacterial species. Among the bacteriocins pediocin-like bacteriocins have a significant inhibitory activity on the foodborne pathogens especially on Listeria monocytogenes. This study aims to select a simple and usable purification method to purify/concentrate the antimicrobial peptide and characterization of the bacteriocin produced by Pediococcus acidilactici 13 by using proteomic approaches which is a recent omic technology. For purification dialysis, ultrafiltration method was used, and as a result of this study the bacteriocin activity reached 819,200 AU/mL from 102,400 AU/mL initially. Two dimensional gel electrophoresis and then matrix-assisted laser desorption ionization/time of flight mass spectrometry (MALDI-TOF MS) analysis were carried out to identify the current bacteriocin and related proteins. Obtained data revealed similarity to pediocin PA-1 transport/processing ATP-binding protein PedD (accession number: P36497), pediocin operon PedC (accession number: Q68GC4) and bacteriocin pediocin PA-1 (accession number: P29430) from UniProtKB/Swiss-Prot databank, thus the bacteriocin produced by P. acidilactici 13 is considered similar to pediocin PA-1.

  12. Real-Time Particle Mass Spectrometry Based on Resonant Micro Strings

    DEFF Research Database (Denmark)

    Schmid, Silvan; Dohn, Søren; Boisen, Anja

    2010-01-01

    by measuring the resonant frequency shifts of the first two bending modes. The method has been tested by detecting the mass spectrum of micro particles placed on a micro string. This method enables real-time mass spectrometry necessary for applications such as personal monitoring devices for the assessment......Micro- and nanomechanical resonators are widely being used as mass sensors due to their unprecedented mass sensitivity. We present a simple closed-form expression which allows a fast and quantitative calculation of the position and mass of individual particles placed on a micro or nano string...

  13. RAId_DbS: mass-spectrometry based peptide identification web server with knowledge integration

    Directory of Open Access Journals (Sweden)

    Ogurtsov Aleksey Y

    2008-10-01

    Full Text Available Abstract Background Existing scientific literature is a rich source of biological information such as disease markers. Integration of this information with data analysis may help researchers to identify possible controversies and to form useful hypotheses for further validations. In the context of proteomics studies, individualized proteomics era may be approached through consideration of amino acid substitutions/modifications as well as information from disease studies. Integration of such information with peptide searches facilitates speedy, dynamic information retrieval that may significantly benefit clinical laboratory studies. Description We have integrated from various sources annotated single amino acid polymorphisms, post-translational modifications, and their documented disease associations (if they exist into one enhanced database per organism. We have also augmented our peptide identification software RAId_DbS to take into account this information while analyzing a tandem mass spectrum. In principle, one may choose to respect or ignore the correlation of amino acid polymorphisms/modifications within each protein. The former leads to targeted searches and avoids scoring of unnecessary polymorphism/modification combinations; the latter explores possible polymorphisms in a controlled fashion. To facilitate new discoveries, RAId_DbS also allows users to conduct searches permitting novel polymorphisms as well as to search a knowledge database created by the users. Conclusion We have finished constructing enhanced databases for 17 organisms. The web link to RAId_DbS and the enhanced databases is http://www.ncbi.nlm.nih.gov/CBBResearch/qmbp/RAId_DbS/index.html. The relevant databases and binaries of RAId_DbS for Linux, Windows, and Mac OS X are available for download from the same web page.

  14. Applying mass spectrometry-based qualitative proteomics to human amygdaloid complex

    Directory of Open Access Journals (Sweden)

    Joaquín eFernández-Irigoyen

    2014-03-01

    Full Text Available The amygdaloid complex is a key brain structure involved in the expression of behaviours and emotions such as learning, fear, and anxiety. Brain diseases including depression, epilepsy, autism, schizophrenia, and Alzheimer`s disease, have been associated with amygdala dysfunction. For several decades, neuroanatomical, neurophysiological, volumetric, and cognitive approaches have been the gold standard techniques employed to characterize the amygdala functionality. However, little attention has been focused specifically on the molecular composition of the human amygdala from the perspective of proteomics. We have performed a global proteome analysis employing protein and peptide fractionation methods followed by nano-liquid chromatography tandem mass spectrometry (nanoLC-MS/MS, detecting expression of at least 1820 protein species in human amygdala, corresponding to 1814 proteins which represent a 9-fold increase in proteome coverage with respect to previous proteomic profiling of the rat amygdala. Gene ontology analysis were used to determine biological process represented in human amygdala highlighting molecule transport, nucleotide binding, and oxidoreductase and GTPase activities. Bioinformatic analyses have revealed that nearly 4% of identified proteins have been previously associated to neurodegenerative syndromes, and 26% of amygdaloid proteins were also found to be present in cerebrospinal fluid (CSF. In particular, a subset of amygdaloid proteins was mainly involved in axon guidance, synaptic vesicle release, L1CAM interactome, and signaling pathways transduced by NGF and NCAM1. Taken together, our data contributes to the repertoire of the human brain proteome, serving as a reference library to provide basic information for understanding the neurobiology of the human amygdala.

  15. Mass spectrometry-based proteomic analysis of human liver cytochrome(s) P450

    Energy Technology Data Exchange (ETDEWEB)

    Shrivas, Kamlesh; Mindaye, Samuel T.; Getie-Kebtie, Melkamu; Alterman, Michail A., E-mail: Michail.Alterman@fda.hhs.gov

    2013-02-15

    The major objective of personalized medicine is to select optimized drug therapies and to a large degree such mission is determined by the expression profiles of cytochrome(s) P450 (CYP). Accordingly, a proteomic case study in personalized medicine is provided by the superfamily of cytochromes P450. Our knowledge about CYP isozyme expression on a protein level is very limited and based exclusively on DNA/mRNA derived data. Such information is not sufficient because transcription and translation events do not lead to correlated levels of expressed proteins. Here we report expression profiles of CYPs in human liver obtained by mass spectrometry (MS)-based proteomic approach. We analyzed 32 samples of human liver microsomes (HLM) of different sexes, ages and ethnicity along with samples of recombinant human CYPs. We have experimentally confirmed that each CYP isozyme can be effectively differentiated by their unique isozyme-specific tryptic peptide(s). Trypsin digestion patterns for almost 30 human CYP isozymes were established. Those findings should assist in selecting tryptic peptides suitable for MS-based quantitation. The data obtained demonstrate remarkable differences in CYP expression profiles. CYP2E1, CYP2C8 and CYP4A11 were the only isozymes found in all HLM samples. Female and pediatric HLM samples revealed much more diverse spectrum of expressed CYPs isozymes compared to male HLM. We have confirmed expression of a number of “rare” CYP (CYP2J2, CYP4B1, CYP4V2, CYP4F3, CYP4F11, CYP8B1, CYP19A1, CYP24A1 and CYP27A1) and obtained first direct experimental data showing expression of such CYPs as CYP2F1, CYP2S1, CYP2W1, CYP4A22, CYP4X1, and CYP26A1 on a protein level. - Highlights: ► First detailed proteomic analysis of CYP isozymes expression in human liver ► Trypsin digestion patterns for almost 30 human CYP isozymes established ► The data obtained demonstrate remarkable differences in CYP expression profiles. ► Female HLM samples revealed more

  16. Mass spectrometry-based proteomic analysis of human liver cytochrome(s) P450

    International Nuclear Information System (INIS)

    Shrivas, Kamlesh; Mindaye, Samuel T.; Getie-Kebtie, Melkamu; Alterman, Michail A.

    2013-01-01

    The major objective of personalized medicine is to select optimized drug therapies and to a large degree such mission is determined by the expression profiles of cytochrome(s) P450 (CYP). Accordingly, a proteomic case study in personalized medicine is provided by the superfamily of cytochromes P450. Our knowledge about CYP isozyme expression on a protein level is very limited and based exclusively on DNA/mRNA derived data. Such information is not sufficient because transcription and translation events do not lead to correlated levels of expressed proteins. Here we report expression profiles of CYPs in human liver obtained by mass spectrometry (MS)-based proteomic approach. We analyzed 32 samples of human liver microsomes (HLM) of different sexes, ages and ethnicity along with samples of recombinant human CYPs. We have experimentally confirmed that each CYP isozyme can be effectively differentiated by their unique isozyme-specific tryptic peptide(s). Trypsin digestion patterns for almost 30 human CYP isozymes were established. Those findings should assist in selecting tryptic peptides suitable for MS-based quantitation. The data obtained demonstrate remarkable differences in CYP expression profiles. CYP2E1, CYP2C8 and CYP4A11 were the only isozymes found in all HLM samples. Female and pediatric HLM samples revealed much more diverse spectrum of expressed CYPs isozymes compared to male HLM. We have confirmed expression of a number of “rare” CYP (CYP2J2, CYP4B1, CYP4V2, CYP4F3, CYP4F11, CYP8B1, CYP19A1, CYP24A1 and CYP27A1) and obtained first direct experimental data showing expression of such CYPs as CYP2F1, CYP2S1, CYP2W1, CYP4A22, CYP4X1, and CYP26A1 on a protein level. - Highlights: ► First detailed proteomic analysis of CYP isozymes expression in human liver ► Trypsin digestion patterns for almost 30 human CYP isozymes established ► The data obtained demonstrate remarkable differences in CYP expression profiles. ► Female HLM samples revealed more

  17. Computational and statistical methods for high-throughput mass spectrometry-based PTM analysis

    DEFF Research Database (Denmark)

    Schwämmle, Veit; Vaudel, Marc

    2017-01-01

    Cell signaling and functions heavily rely on post-translational modifications (PTMs) of proteins. Their high-throughput characterization is thus of utmost interest for multiple biological and medical investigations. In combination with efficient enrichment methods, peptide mass spectrometry analy...

  18. Laser microdissection and mass spectrometry-based proteomics aids the diagnosis and typing of renal amyloidosis.

    Science.gov (United States)

    Sethi, Sanjeev; Vrana, Julie A; Theis, Jason D; Leung, Nelson; Sethi, Anjali; Nasr, Samih H; Fervenza, Fernando C; Cornell, Lynn D; Fidler, Mary E; Dogan, Ahmet

    2012-07-01

    Accurate diagnosis and typing of renal amyloidosis is critical for prognosis, genetic counseling, and treatment. Laser microdissection and mass spectrometry are emerging techniques for the analysis and diagnosis of many renal diseases. Here we present the results of laser microdissection and mass spectrometry performed on 127 cases of renal amyloidosis during 2008-2010. We found the following proteins in the amyloid deposits: immunoglobulin light and heavy chains, secondary reactive serum amyloid A protein, leukocyte cell-derived chemotaxin-2, fibrinogen-α chain, transthyretin, apolipoprotein A-I and A-IV, gelsolin, and β-2 microglobulin. Thus, laser microdissection of affected areas within the kidney followed by mass spectrometry provides a direct test of the composition of the deposit and forms a useful ancillary technique for the accurate diagnosis and typing of renal amyloidosis in a single procedure.

  19. Systemic sclerosis biomarkers discovered using mass-spectrometry-based proteomics: a systematic review.

    Science.gov (United States)

    Bălănescu, Paul; Lădaru, Anca; Bălănescu, Eugenia; Băicuş, Cristian; Dan, Gheorghe Andrei

    2014-08-01

    Systemic sclerosis (SSc) is an autoimmune disease with incompletely known physiopathology. There is a great challenge to predict its course and therapeutic response using biomarkers. To critically review proteomic biomarkers discovered from biological specimens from systemic sclerosis patients using mass spectrometry technologies. Medline and Embase databases were searched in February 2014. Out of the 199 records retrieved, a total of 20 records were included, identifying 116 candidate proteomic biomarkers. Research in SSc proteomic biomarkers should focus on biomarker validation, as there are valuable mass-spectrometry proteomics studies in the literature.

  20. Application of mass spectrometry based electronic nose and chemometrics for fingerprinting radiation treatment

    International Nuclear Information System (INIS)

    Gupta, Sumit; Variyar, Prasad S.; Sharma, Arun

    2015-01-01

    Volatile compounds were isolated from apples and grapes employing solid phase micro extraction (SPME) and subsequently analyzed by GC/MS equipped with a transfer line without stationary phase. Single peak obtained was integrated to obtain total mass spectrum of the volatile fraction of samples. A data matrix having relative abundance of all mass-to-charge ratios was subjected to principal component analysis (PCA) and linear discriminant analysis (LDA) to identify radiation treatment. PCA results suggested that there is sufficient variability between control and irradiated samples to build classification models based on supervised techniques. LDA successfully aided in segregating control from irradiated samples at all doses (0.1, 0.25, 0.5, 1.0, 1.5, 2.0 kGy). SPME-MS with chemometrics was successfully demonstrated as simple screening method for radiation treatment. - Highlights: • Total mass spectra obtained from HS-MS for control and irradiated fruits. • Grapes and apples are chosen for present study. • Total mass spectrum was analyzed by two chemometric techniques (PCA and LDA). • Successful segregation of control and irradiated samples achieved using chemometrics

  1. Substrate and cofactor binding to nitrile reductase : A mass spectrometry based study

    NARCIS (Netherlands)

    Gjonaj, L.; Pinkse, M.W.H.; Fernandez Fueyo, E.; Hollmann, F.; Hanefeld, U.

    2016-01-01

    Nitrile reductases catalyse a two-step reduction of nitriles to amines. This requires the binding of two NADPH molecules during one catalytic cycle. For the nitrile reductase from E. coli (EcoNR) mass spectrometry studies of the catalytic mechanism were performed. EcoNR is dimeric and has no Rossman

  2. Application of mass spectrometry based electronic nose and chemometrics for fingerprinting radiation treatment

    Science.gov (United States)

    Gupta, Sumit; Variyar, Prasad S.; Sharma, Arun

    2015-01-01

    Volatile compounds were isolated from apples and grapes employing solid phase micro extraction (SPME) and subsequently analyzed by GC/MS equipped with a transfer line without stationary phase. Single peak obtained was integrated to obtain total mass spectrum of the volatile fraction of samples. A data matrix having relative abundance of all mass-to-charge ratios was subjected to principal component analysis (PCA) and linear discriminant analysis (LDA) to identify radiation treatment. PCA results suggested that there is sufficient variability between control and irradiated samples to build classification models based on supervised techniques. LDA successfully aided in segregating control from irradiated samples at all doses (0.1, 0.25, 0.5, 1.0, 1.5, 2.0 kGy). SPME-MS with chemometrics was successfully demonstrated as simple screening method for radiation treatment.

  3. Reproducibility of mass spectrometry based protein profiles for diagnosis of breast cancer across clinical studies

    DEFF Research Database (Denmark)

    Callesen, Anne Kjærgaard; Vach, Werner; Jørgensen, Per E

    2008-01-01

    Serum protein profiling by mass spectrometry has achieved attention as a promising technology in oncoproteomics. We performed a systematic review of published reports on protein profiling as a diagnostic tool for breast cancer. The MEDLINE, EMBASE, and COCHRANE databases were searched for original...... studies reporting discriminatory protein peaks for breast cancer as either protein identity or as m/ z values in the period from January 1995 to October 2006. To address the important aspect of reproducibility of mass spectrometry data across different clinical studies, we compared the published lists...... of potential discriminatory peaks with those peaks detected in an original MALDI MS protein profiling study performed by our own research group. A total of 20 protein/peptide profiling studies were eligible for inclusion in the systematic review. Only 3 reports included information on protein identity...

  4. Mass spectrometry-based methods for detection and differentiation of botulinum neurotoxins

    Science.gov (United States)

    Schmidt, Jurgen G [Los Alamos, NM; Boyer, Anne E [Atlanta, GA; Kalb, Suzanne R [Atlanta, GA; Moura, Hercules [Tucker, GA; Barr, John R [Suwannee, GA; Woolfitt, Adrian R [Atlanta, GA

    2009-11-03

    The present invention is directed to a method for detecting the presence of clostridial neurotoxins in a sample by mixing a sample with a peptide that can serve as a substrate for proteolytic activity of a clostridial neurotoxin; and measuring for proteolytic activity of a clostridial neurotoxin by a mass spectroscopy technique. In one embodiment, the peptide can have an affinity tag attached at two or more sites.

  5. Development and validation of mass spectrometry-based methods for food quality and food safety assessment

    OpenAIRE

    Bignardi, Chiara

    2014-01-01

    In this PhD thesis, analytical chemistry plays a significant role in the assessment of food quality and safety; in particular, three different topics have been addressed to and they are presented into three chapters in which different analytical methodologies have been developed, validated and applied successfully in different topics of food chemistry research. The first chapter is focused on an innovative analytical technique, capillary zone electrophoresis coupled to tandem mass spectrom...

  6. Mass Spectrometry-Based Serum Proteomics for Biomarker Discovery and Validation.

    Science.gov (United States)

    Bhosale, Santosh D; Moulder, Robert; Kouvonen, Petri; Lahesmaa, Riitta; Goodlett, David R

    2017-01-01

    Blood protein measurements are used frequently in the clinic in the assessment of patient health. Nevertheless, there remains the need for new biomarkers with better diagnostic specificities. With the advent of improved technology for bioanalysis and the growth of biobanks including collections from specific disease risk cohorts, the plasma proteome has remained a target of proteomics research toward the characterization of disease-related biomarkers. The following protocol presents a workflow for serum/plasma proteomics including details of sample preparation both with and without immunoaffinity depletion of the most abundant plasma proteins and methodology for selected reaction monitoring mass spectrometry validation.

  7. Biomarkers in Alzheimer’s Disease Analysis by Mass Spectrometry-Based Proteomics

    Directory of Open Access Journals (Sweden)

    Yahui Liu

    2014-05-01

    Full Text Available Alzheimer’s disease (AD is a common chronic and destructive disease. The early diagnosis of AD is difficult, thus the need for clinically applicable biomarkers development is growing rapidly. There are many methods to biomarker discovery and identification. In this review, we aim to summarize Mass spectrometry (MS-based proteomics studies on AD and discuss thoroughly the methods to identify candidate biomarkers in cerebrospinal fluid (CSF and blood. This review will also discuss the potential research areas on biomarkers.

  8. The Recent Developments in Sample Preparation for Mass Spectrometry-Based Metabolomics.

    Science.gov (United States)

    Gong, Zhi-Gang; Hu, Jing; Wu, Xi; Xu, Yong-Jiang

    2017-07-04

    Metabolomics is a critical member in systems biology. Although great progress has been achieved in metabolomics, there are still some problems in sample preparation, data processing and data interpretation. In this review, we intend to explore the roles, challenges and trends in sample preparation for mass spectrometry- (MS-) based metabolomics. The newly emerged sample preparation methods were also critically examined, including laser microdissection, in vivo sampling, dried blood spot, microwave, ultrasound and enzyme-assisted extraction, as well as microextraction techniques. Finally, we provide some conclusions and perspectives for sample preparation in MS-based metabolomics.

  9. Quantitative Mass Spectrometry-Based Proteomic Profiling for Precision Medicine in Prostate Cancer

    DEFF Research Database (Denmark)

    Flores-Morales, Amilcar; Iglesias-Gato, Diego

    2017-01-01

    are proteins, including the widely-used prostate-specific antigen (PSA). Recent developments in mass spectrometry allow the identification and quantification of thousands of proteins and posttranslational modifications from small amounts of biological material, including formalin-fixed paraffin......Prostate cancer (PCa) is one of the most frequently diagnosed cancer among men in the western societies. Many PCa patients bear tumors that will not threat their lives if left untreated or if treatment is delayed. Our inability for early identification of these patients has resulted in massive...

  10. Open source libraries and frameworks for mass spectrometry based proteomics: A developer's perspective☆

    Science.gov (United States)

    Perez-Riverol, Yasset; Wang, Rui; Hermjakob, Henning; Müller, Markus; Vesada, Vladimir; Vizcaíno, Juan Antonio

    2014-01-01

    Data processing, management and visualization are central and critical components of a state of the art high-throughput mass spectrometry (MS)-based proteomics experiment, and are often some of the most time-consuming steps, especially for labs without much bioinformatics support. The growing interest in the field of proteomics has triggered an increase in the development of new software libraries, including freely available and open-source software. From database search analysis to post-processing of the identification results, even though the objectives of these libraries and packages can vary significantly, they usually share a number of features. Common use cases include the handling of protein and peptide sequences, the parsing of results from various proteomics search engines output files, and the visualization of MS-related information (including mass spectra and chromatograms). In this review, we provide an overview of the existing software libraries, open-source frameworks and also, we give information on some of the freely available applications which make use of them. This article is part of a Special Issue entitled: Computational Proteomics in the Post-Identification Era. Guest Editors: Martin Eisenacher and Christian Stephan. PMID:23467006

  11. Open source libraries and frameworks for mass spectrometry based proteomics: a developer's perspective.

    Science.gov (United States)

    Perez-Riverol, Yasset; Wang, Rui; Hermjakob, Henning; Müller, Markus; Vesada, Vladimir; Vizcaíno, Juan Antonio

    2014-01-01

    Data processing, management and visualization are central and critical components of a state of the art high-throughput mass spectrometry (MS)-based proteomics experiment, and are often some of the most time-consuming steps, especially for labs without much bioinformatics support. The growing interest in the field of proteomics has triggered an increase in the development of new software libraries, including freely available and open-source software. From database search analysis to post-processing of the identification results, even though the objectives of these libraries and packages can vary significantly, they usually share a number of features. Common use cases include the handling of protein and peptide sequences, the parsing of results from various proteomics search engines output files, and the visualization of MS-related information (including mass spectra and chromatograms). In this review, we provide an overview of the existing software libraries, open-source frameworks and also, we give information on some of the freely available applications which make use of them. This article is part of a Special Issue entitled: Computational Proteomics in the Post-Identification Era. Guest Editors: Martin Eisenacher and Christian Stephan. Copyright © 2013 Elsevier B.V. All rights reserved.

  12. Hybrid Imaging Labels: Providing the Link Between Mass Spectrometry-Based Molecular Pathology and Theranostics

    Science.gov (United States)

    Buckle, Tessa; van der Wal, Steffen; van Malderen, Stijn J.M.; Müller, Larissa; Kuil, Joeri; van Unen, Vincent; Peters, Ruud J.B.; van Bemmel, Margaretha E.M.; McDonnell, Liam A.; Velders, Aldrik H.; Koning, Frits; Vanhaeke, Frank; van Leeuwen, Fijs W. B.

    2017-01-01

    Background: Development of theranostic concepts that include inductively coupled plasma mass spectrometry (ICP-MS) and laser ablation ICP-MS (LA-ICP-MS) imaging can be hindered by the lack of a direct comparison to more standardly used methods for in vitro and in vivo evaluation; e.g. fluorescence or nuclear medicine. In this study a bimodal (or rather, hybrid) tracer that contains both a fluorescent dye and a chelate was used to evaluate the existence of a direct link between mass spectrometry (MS) and in vitro and in vivo molecular imaging findings using fluorescence and radioisotopes. At the same time, the hybrid label was used to determine whether the use of a single isotope label would allow for MS-based diagnostics. Methods: A hybrid label that contained both a DTPA chelate (that was coordinated with either 165Ho or 111In) and a Cy5 fluorescent dye was coupled to the chemokine receptor 4 (CXCR4) targeting peptide Ac-TZ14011 (hybrid-Cy5-Ac-TZ4011). This receptor targeting tracer was used to 1) validate the efficacy of (165Ho-based) mass-cytometry in determining the receptor affinity via comparison with fluorescence-based flow cytometry (Cy5), 2) evaluate the microscopic binding pattern of the tracer in tumor cells using both fluorescence confocal imaging (Cy5) and LA-ICP-MS-imaging (165Ho), 3) compare in vivo biodistribution patterns obtained with ICP-MS (165Ho) and radiodetection (111In) after intravenous administration of hybrid-Cy5-Ac-TZ4011 in tumor-bearing mice. Finally, LA-ICP-MS-imaging (165Ho) was linked to fluorescence-based analysis of excised tissue samples (Cy5). Results: Analysis with both mass-cytometry and flow cytometry revealed a similar receptor affinity, respectively 352 ± 141 nM and 245 ± 65 nM (p = 0.08), but with a much lower detection sensitivity for the first modality. In vitro LA-ICP-MS imaging (165Ho) enabled clear discrimination between CXCR4 positive and negative cells, but fluorescence microscopy was required to determine the

  13. High-field asymmetric waveform ion mobility spectrometry for mass spectrometry-based proteomics.

    Science.gov (United States)

    Swearingen, Kristian E; Moritz, Robert L

    2012-10-01

    High-field asymmetric waveform ion mobility spectrometry (FAIMS) is an atmospheric pressure ion mobility technique that separates gas-phase ions by their behavior in strong and weak electric fields. FAIMS is easily interfaced with electrospray ionization and has been implemented as an additional separation mode between liquid chromatography (LC) and mass spectrometry (MS) in proteomic studies. FAIMS separation is orthogonal to both LC and MS and is used as a means of on-line fractionation to improve the detection of peptides in complex samples. FAIMS improves dynamic range and concomitantly the detection limits of ions by filtering out chemical noise. FAIMS can also be used to remove interfering ion species and to select peptide charge states optimal for identification by tandem MS. Here, the authors review recent developments in LC-FAIMS-MS and its application to MS-based proteomics.

  14. Advances in mass spectrometry-based cancer research and analysis: from cancer proteomics to clinical diagnostics.

    Science.gov (United States)

    Timms, John F; Hale, Oliver J; Cramer, Rainer

    2016-06-01

    The last 20 years have seen significant improvements in the analytical capabilities of biological mass spectrometry (MS). Studies using advanced MS have resulted in new insights into cell biology and the etiology of diseases as well as its use in clinical applications. This review discusses recent developments in MS-based technologies and their cancer-related applications with a focus on proteomics. It also discusses the issues around translating the research findings to the clinic and provides an outline of where the field is moving. Expert commentary: Proteomics has been problematic to adapt for the clinical setting. However, MS-based techniques continue to demonstrate potential in novel clinical uses beyond classical cancer proteomics.

  15. High Field Asymmetric Waveform Ion Mobility Spectrometry (FAIMS) for Mass Spectrometry-Based Proteomics

    Science.gov (United States)

    Swearingen, Kristian E.; Moritz, Robert L.

    2013-01-01

    SUMMARY High field asymmetric waveform ion mobility spectrometry (FAIMS) is an atmospheric pressure ion mobility technique that separates gas-phase ions by their behavior in strong and weak electric fields. FAIMS is easily interfaced with electrospray ionization and has been implemented as an additional separation mode between liquid chromatography (LC) and mass spectrometry (MS) in proteomic studies. FAIMS separation is orthogonal to both LC and MS and is used as a means of on-line fractionation to improve detection of peptides in complex samples. FAIMS improves dynamic range and concomitantly the detection limits of ions by filtering out chemical noise. FAIMS can also be used to remove interfering ion species and to select peptide charge states optimal for identification by tandem MS. Here, we review recent developments in LC-FAIMS-MS and its application to MS-based proteomics. PMID:23194268

  16. Fast mass spectrometry-based enantiomeric excess determination of proteinogenic amino acids.

    Science.gov (United States)

    Fleischer, Heidi; Thurow, Kerstin

    2013-03-01

    A rapid determination of the enantiomeric excess of proteinogenic amino acids is of great importance in various fields of chemical and biologic research and industries. Owing to their different biologic effects, enantiomers are interesting research subjects in drug development for the design of new and more efficient pharmaceuticals. Usually, the enantiomeric composition of amino acids is determined by conventional analytical methods such as liquid or gas chromatography or capillary electrophoresis. These analytical techniques do not fulfill the requirements of high-throughput screening due to their relative long analysis times. The method presented allows a fast analysis of chiral amino acids without previous time consuming chromatographic separation. The analytical measurements base on parallel kinetic resolution with pseudoenantiomeric mass tagged auxiliaries and were carried out by mass spectrometry with electrospray ionization. All 19 chiral proteinogenic amino acids were tested and Pro, Ser, Trp, His, and Glu were selected as model substrates for verification measurements. The enantiomeric excesses of amino acids with non-polar and aliphatic side chains as well as Trp and Phe (aromatic side chains) were determined with maximum deviations of the expected value less than or equal to 10ee%. Ser, Cys, His, Glu, and Asp were determined with deviations lower or equal to 14ee% and the enantiomeric excess of Tyr were calculated with 17ee% deviation. The total screening process is fully automated from the sample pretreatment to the data processing. The method presented enables fast measurement times about 1.38 min per sample and is applicable in the scope of high-throughput screenings.

  17. Recent mass spectrometry-based techniques and considerations for disulfide bond characterization in proteins.

    Science.gov (United States)

    Lakbub, Jude C; Shipman, Joshua T; Desaire, Heather

    2018-04-01

    Disulfide bonds are important structural moieties of proteins: they ensure proper folding, provide stability, and ensure proper function. With the increasing use of proteins for biotherapeutics, particularly monoclonal antibodies, which are highly disulfide bonded, it is now important to confirm the correct disulfide bond connectivity and to verify the presence, or absence, of disulfide bond variants in the protein therapeutics. These studies help to ensure safety and efficacy. Hence, disulfide bonds are among the critical quality attributes of proteins that have to be monitored closely during the development of biotherapeutics. However, disulfide bond analysis is challenging because of the complexity of the biomolecules. Mass spectrometry (MS) has been the go-to analytical tool for the characterization of such complex biomolecules, and several methods have been reported to meet the challenging task of mapping disulfide bonds in proteins. In this review, we describe the relevant, recent MS-based techniques and provide important considerations needed for efficient disulfide bond analysis in proteins. The review focuses on methods for proper sample preparation, fragmentation techniques for disulfide bond analysis, recent disulfide bond mapping methods based on the fragmentation techniques, and automated algorithms designed for rapid analysis of disulfide bonds from liquid chromatography-MS/MS data. Researchers involved in method development for protein characterization can use the information herein to facilitate development of new MS-based methods for protein disulfide bond analysis. In addition, individuals characterizing biotherapeutics, especially by disulfide bond mapping in antibodies, can use this review to choose the best strategies for disulfide bond assignment of their biologic products. Graphical Abstract This review, describing characterization methods for disulfide bonds in proteins, focuses on three critical components: sample preparation, mass

  18. Mass Spectrometry-based Assay for High Throughput and High Sensitivity Biomarker Verification

    Energy Technology Data Exchange (ETDEWEB)

    Guo, Xuejiang; Tang, Keqi

    2017-06-14

    Searching for disease specific biomarkers has become a major undertaking in the biomedical research field as the effective diagnosis, prognosis and treatment of many complex human diseases are largely determined by the availability and the quality of the biomarkers. A successful biomarker as an indicator to a specific biological or pathological process is usually selected from a large group of candidates by a strict verification and validation process. To be clinically useful, the validated biomarkers must be detectable and quantifiable by the selected testing techniques in their related tissues or body fluids. Due to its easy accessibility, protein biomarkers would ideally be identified in blood plasma or serum. However, most disease related protein biomarkers in blood exist at very low concentrations (<1ng/mL) and are “masked” by many none significant species at orders of magnitude higher concentrations. The extreme requirements of measurement sensitivity, dynamic range and specificity make the method development extremely challenging. The current clinical protein biomarker measurement primarily relies on antibody based immunoassays, such as ELISA. Although the technique is sensitive and highly specific, the development of high quality protein antibody is both expensive and time consuming. The limited capability of assay multiplexing also makes the measurement an extremely low throughput one rendering it impractical when hundreds to thousands potential biomarkers need to be quantitatively measured across multiple samples. Mass spectrometry (MS)-based assays have recently shown to be a viable alternative for high throughput and quantitative candidate protein biomarker verification. Among them, the triple quadrupole MS based assay is the most promising one. When it is coupled with liquid chromatography (LC) separation and electrospray ionization (ESI) source, a triple quadrupole mass spectrometer operating in a special selected reaction monitoring (SRM) mode

  19. Mass spectrometry-based bacterial proteomics: focus on dermatological associated microbial pathogens

    Directory of Open Access Journals (Sweden)

    Youcef eSoufi

    2016-02-01

    Full Text Available The composition of human skin acts as a natural habitat for various bacterial species that function in a commensal and symbiotic fashion. In a healthy individual, bacterial flora serves to protect the host. Under certain conditions such as minor trauma, impaired host immunity, or environmental factors, the risk of developing skin infections is increased. Although a large majority of bacterial associated skin infections are common, a portion can potentially manifest into clinically significant morbidity. For example, Gram positive species that typically reside on the skin such as Staphylococcus and Streptococcus can cause numerous epidermal (impetigo, ecthyma and dermal (cellulitis, necrotizing fasciitis, erysipelas skin infections. Moreover, the increasing incidence of bacterial antibiotic resistance represents a serious challenge to modern medicine and threatens the health care system. Therefore, it is critical to develop tools and strategies that can allow us to better elucidate the nature and mechanism of bacterial virulence. To this end, mass spectrometry (MS-based proteomics has been revolutionizing biomedical research, and has positively impacted the microbiology field. Advances in MS technologies have paved the way for numerous bacterial proteomes and their respective post translational modifications (PTMs to be accurately identified and quantified in a high throughput and robust fashion. This technological platform offers critical information with regards to signal transduction, adherence, and microbial-host interactions associated with bacterial pathogenesis. This mini-review serves to highlight the current progress proteomics has contributed towards the understanding of bacteria that are associated with skin related diseases, infections, and antibiotic resistance.

  20. Data set for the mass spectrometry based exoproteome analysis of Aspergillus flavus isolates

    Directory of Open Access Journals (Sweden)

    Ramu Muthu Selvam

    2015-03-01

    Full Text Available Aspergillus flavus is one of the predominant causative organisms of mycotic keratitis in tropical parts of the world. Extracellular proteins are the earliest proteins that come in contact with the host and have a role in the infection process. Exoproteins of A. flavus isolated from infected cornea, sputum and a saprophyte were pooled and identified using high resolution mass spectrometry in order to get the total exoproteome from cultures isolated from different sources. A total of 637 proteins was identified from the pooled A. flavus exoproteome. Analysis based on GO annotations of the 637 identified proteins revealed that hydrolases form the predominant class of proteins in the exoproteome. Interestingly, a greater proportion of the exoproteins seem to be secreted through the non-classical pathways. This data represent the first in-depth analysis of the representative A. flavus exoproteome of a large set of isolates from distinct sources. This data have been deposited to the ProteomeXchange with identifier PXD001296.

  1. Automated Sample Preparation Platform for Mass Spectrometry-Based Plasma Proteomics and Biomarker Discovery

    Directory of Open Access Journals (Sweden)

    Vilém Guryča

    2014-03-01

    Full Text Available The identification of novel biomarkers from human plasma remains a critical need in order to develop and monitor drug therapies for nearly all disease areas. The discovery of novel plasma biomarkers is, however, significantly hampered by the complexity and dynamic range of proteins within plasma, as well as the inherent variability in composition from patient to patient. In addition, it is widely accepted that most soluble plasma biomarkers for diseases such as cancer will be represented by tissue leakage products, circulating in plasma at low levels. It is therefore necessary to find approaches with the prerequisite level of sensitivity in such a complex biological matrix. Strategies for fractionating the plasma proteome have been suggested, but improvements in sensitivity are often negated by the resultant process variability. Here we describe an approach using multidimensional chromatography and on-line protein derivatization, which allows for higher sensitivity, whilst minimizing the process variability. In order to evaluate this automated process fully, we demonstrate three levels of processing and compare sensitivity, throughput and reproducibility. We demonstrate that high sensitivity analysis of the human plasma proteome is possible down to the low ng/mL or even high pg/mL level with a high degree of technical reproducibility.

  2. Quantification of mutant SPOP proteins in prostate cancer using mass spectrometry-based targeted proteomics

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Hui; Barbieri, Christopher E.; He, Jintang; Gao, Yuqian; Shi, Tujin; Wu, Chaochao; Schepmoes, Athena A.; Fillmore, Thomas L.; Chae, Sung-Suk; Huang, Dennis; Mosquera, Juan Miguel; Qian, Wei-Jun; Smith, Richard D.; Srivastava, Sudhir; Kagan, Jacob; Camp, David G.; Rodland, Karin D.; Rubin, Mark A.; Liu, Tao

    2017-08-15

    Speckle-type POZ protein (SPOP) is an E3 ubiquitin ligase adaptor protein that functions as a potential tumor suppressor, and SPOP mutations have been identified in ~10% of human prostate cancers. However, it remains unclear if mutant SPOP proteins can be utilized as biomarkers for early detection, diagnosis, prognosis or targeted therapy of prostate cancer. Moreover, the SPOP mutation sites are distributed in a relatively short region where multiple lysine residues, posing significant challenges for bottom-up proteomics analysis of the SPOP mutations. To address this issue, PRISM (high-pressure, high-resolution separations coupled with intelligent selection and multiplexing)-SRM (selected reaction monitoring) mass spectrometry assays have been developed for quantifying wild-type SPOP protein and 11 prostate cancer-derived SPOP mutations. Despite inherent limitations due to amino acid sequence constraints, all the PRISM-SRM assays developed using Arg-C digestion showed a linear dynamic range of at least two orders of magnitude, with limits of quantification range from 0.1 to 1 fmol/μg of total protein in the cell lysate. Applying these SRM assays to analyze HEK293T cells with and without expression of the three most frequent SPOP mutations in prostate cancer (Y87N, F102C or F133V) led to confident detection of all three SPOP mutations in corresponding positive cell lines but not in the negative cell lines. Expression of the F133V mutation and wild-type SPOP was at much lower levels compared to that of F102C and Y87N mutations; however, at present it is unknown if this also affects the activity of the SPOP protein. In summary, PRISM-SRM enables multiplexed, isoform-specific detection of mutant SPOP proteins in cell lysates, which holds great potential in biomarker development for prostate cancer.

  3. Identifying Predictors of Taxane-Induced Peripheral Neuropathy Using Mass Spectrometry-Based Proteomics Technology.

    Directory of Open Access Journals (Sweden)

    Emily I Chen

    Full Text Available Major advances in early detection and therapy have significantly increased the survival of breast cancer patients. Unfortunately, most cancer therapies are known to carry a substantial risk of adverse long-term treatment-related effects. Little is known about patient susceptibility to severe side effects after chemotherapy. Chemotherapy-induced peripheral neuropathy (CIPN is a common side effect of taxanes. Recent advances in genome-wide genotyping and sequencing technologies have supported the discoveries of a number of pharmacogenetic markers that predict response to chemotherapy. However, effectively implementing these pharmacogenetic markers in the clinic remains a major challenge. On the other hand, recent advances in proteomic technologies incorporating mass spectrometry (MS for biomarker discovery show great promise to provide clinically relevant protein biomarkers. In this study, we evaluated the association between protein content in serum exosomes and severity of CIPN. Women with early stage breast cancer receiving adjuvant taxane chemotherapy were assessed with the FACT-Ntx score and serum was collected before and after the taxane treatment. Based on the change in FACT-Ntx score from baseline to 12 month follow-up, we separated patients into two groups: those who had no change (Group 1, N = 9 and those who had a ≥20% worsening (Group 1, N = 8. MS-based proteomics technology was used to identify proteins present in serum exosomes to determine potential biomarkers. Mann-Whitney-Wilcoxon analysis was applied and maximum FDR was controlled at 20%. From the serum exosomes derived from this cohort, we identified over 700 proteins known to be in different subcellular locations and have different functions. Statistical analysis revealed a 12-protein signature that resulted in a distinct separation between baseline serum samples of both groups (q<0.2 suggesting that the baseline samples can predict subsequent neurotoxicity. These toxicity

  4. Gas chromatography/mass spectrometry based component profiling and quality prediction for Japanese sake.

    Science.gov (United States)

    Mimura, Natsuki; Isogai, Atsuko; Iwashita, Kazuhiro; Bamba, Takeshi; Fukusaki, Eiichiro

    2014-10-01

    Sake is a Japanese traditional alcoholic beverage, which is produced by simultaneous saccharification and alcohol fermentation of polished and steamed rice by Aspergillus oryzae and Saccharomyces cerevisiae. About 300 compounds have been identified in sake, and the contribution of individual components to the sake flavor has been examined at the same time. However, only a few compounds could explain the characteristics alone and most of the attributes still remain unclear. The purpose of this study was to examine the relationship between the component profile and the attributes of sake. Gas chromatography coupled with mass spectrometry (GC/MS)-based non-targeted analysis was employed to obtain the low molecular weight component profile of Japanese sake including both nonvolatile and volatile compounds. Sake attributes and overall quality were assessed by analytical descriptive sensory test and the prediction model of the sensory score from the component profile was constructed by means of orthogonal projections to latent structures (OPLS) regression analysis. Our results showed that 12 sake attributes [ginjo-ka (aroma of premium ginjo sake), grassy/aldehydic odor, sweet aroma/caramel/burnt odor, sulfury odor, sour taste, umami, bitter taste, body, amakara (dryness), aftertaste, pungent/smoothness and appearance] and overall quality were accurately explained by component profiles. In addition, we were able to select statistically significant components according to variable importance on projection (VIP). Our methodology clarified the correlation between sake attribute and 200 low molecular components and presented the importance of each component thus, providing new insights to the flavor study of sake. Copyright © 2014 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

  5. A Comprehensive, Open-source Platform for Mass Spectrometry-based Glycoproteomics Data Analysis.

    Science.gov (United States)

    Liu, Gang; Cheng, Kai; Lo, Chi Y; Li, Jun; Qu, Jun; Neelamegham, Sriram

    2017-11-01

    Glycosylation is among the most abundant and diverse protein post-translational modifications (PTMs) identified to date. The structural analysis of this PTM is challenging because of the diverse monosaccharides which are not conserved among organisms, the branched nature of glycans, their isomeric structures, and heterogeneity in the glycan distribution at a given site. Glycoproteomics experiments have adopted the traditional high-throughput LC-MS n proteomics workflow to analyze site-specific glycosylation. However, comprehensive computational platforms for data analyses are scarce. To address this limitation, we present a comprehensive, open-source, modular software for glycoproteomics data analysis called GlycoPAT (GlycoProteomics Analysis Toolbox; freely available from www.VirtualGlycome.org/glycopat). The program includes three major advances: (1) "SmallGlyPep," a minimal linear representation of glycopeptides for MS n data analysis. This format allows facile serial fragmentation of both the peptide backbone and PTM at one or more locations. (2) A novel scoring scheme based on calculation of the "Ensemble Score (ES)," a measure that scores and rank-orders MS/MS spectrum for N- and O-linked glycopeptides using cross-correlation and probability based analyses. (3) A false discovery rate (FDR) calculation scheme where decoy glycopeptides are created by simultaneously scrambling the amino acid sequence and by introducing artificial monosaccharides by perturbing the original sugar mass. Parallel computing facilities and user-friendly GUIs (Graphical User Interfaces) are also provided. GlycoPAT is used to catalogue site-specific glycosylation on simple glycoproteins, standard protein mixtures and human plasma cryoprecipitate samples in three common MS/MS fragmentation modes: CID, HCD and ETD. It is also used to identify 960 unique glycopeptides in cell lysates from prostate cancer cells. The results show that the simultaneous consideration of peptide and glycan

  6. An improved mass spectrometry-based measurement of NO metabolites in biological fluids.

    Science.gov (United States)

    Yang, Xingbin; Bondonno, Catherine P; Indrawan, Adeline; Hodgson, Jonathan M; Croft, Kevin D

    2013-03-01

    Assessment of NO metabolism in vivo relies on the accurate measurement of its metabolites nitrite (NO(2)(-)), nitrate (NO(3)(-)), and nitrosothiols (RSNOs) in biological fluids. We report a sensitive method to simultaneously determine NO(2)(-) and NO(3)(-) in biological matrixes. Tetraoctylammonium was used to catalyze the complete conversion of NO(2)(-) and NO(3)(-) to stable pentafluorobenzyl (PFB) derivatives directly from aqueous acetone medium before gas chromatography and negative-ion chemical ionization mass spectrometry (GC/NICI/MS). This catalyst dramatically improved the yield of PFB derivatives for NO(2)(-) (4.5 times) and NO(3)(-) (55 times) compared to noncatalyzed derivatization methods. Analysis was performed using (15)N-labeled internal standards by selected-ion monitoring at m/z 46 for fragment NO(2)(-) and m/z 47 for its isotope analogue, (15)NO(2)(-), and m/z 62 for NO(3)(-) and m/z 63 for (15)NO(3)(-). This method allowed specific detection of both PFB derivatives over a wide dynamic range with a limit of detection below 4.5 pg for NO(2)(-) and 2.5 pg for NO(3)(-). After the specific conversion of RSNOs by HgCl(2) to NO(2)(-), this GC/NICI/MS analysis was used to measure RSNOs in plasma. A further comparison with the widely used tri-iodide chemiluminescence (I(3)(-)-CL) assay indicated that the GC/MS assay validated the lower physiological RSNO and nitrite levels reported using I(3)(-)-CL detection compared with values obtained using UV-photolysis methods. Plasma levels of RSNOs determined by GC/MS and I(3)(-)-CL were well correlated (r = 0.8). The improved GC/MS method was successfully used to determine the changes in plasma, urinary, and salivary NO(2)(-) and NO(3)(-) as well as plasma RSNOs in humans after either a low-NO(3)(-) or a high-NO(3)(-) meal. Copyright © 2012 Elsevier Inc. All rights reserved.

  7. Mass-Spectrometry-Based Proteomics Reveals Organ-Specific Expression Patterns To Be Used as Forensic Evidence.

    Science.gov (United States)

    Dammeier, Sascha; Nahnsen, Sven; Veit, Johannes; Wehner, Frank; Ueffing, Marius; Kohlbacher, Oliver

    2016-01-04

    Standard forensic procedures to examine bullets after an exchange of fire include a mechanical or ballistic reconstruction of the event. While this is routine to identify which projectile hit a subject by DNA analysis of biological material on the surface of the projectile, it is rather difficult to determine which projectile caused the lethal injury--often the crucial point with regard to legal proceedings. With respect to fundamental law it is the duty of the public authority to make every endeavor to solve every homicide case. To improve forensic examinations, we present a forensic proteomic method to investigate biological material from a projectile's surface and determine the tissues traversed by it. To obtain a range of relevant samples, different major bovine organs were penetrated with projectiles experimentally. After tryptic "on-surface" digestion, mass-spectrometry-based proteome analysis, and statistical data analysis, we were able to achieve a cross-validated organ classification accuracy of >99%. Different types of anticipated external variables exhibited no prominent influence on the findings. In addition, shooting experiments were performed to validate the results. Finally, we show that these concepts could be applied to a real case of murder to substantially improve the forensic reconstruction.

  8. Classification of Tempranillo wines according to geographic origin: Combination of mass spectrometry based electronic nose and chemometrics

    Energy Technology Data Exchange (ETDEWEB)

    Cynkar, Wies, E-mail: wies.cynkar@awri.com.au [Australian Wine Research Institute, PO Box 197, Glen Osmond, SA 5064 (Australia); Dambergs, Robert [Australian Wine Research Institute, Tasmanian Institute of Agricultural Research, University of Tasmania, Private Bag 98, Hobart Tasmania 7001 (Australia); Smith, Paul; Cozzolino, Daniel [Australian Wine Research Institute, PO Box 197, Glen Osmond, SA 5064 (Australia)

    2010-02-15

    Rapid methods employing instruments such as electronic noses (EN) or gas sensors are used in the food and beverage industries to monitor and assess the composition and quality of products. Similar to other food industries, the wine industry has a clear need for simple, rapid and cost effective techniques for objectively evaluating the quality of grapes, wine and spirits. In this study a mass spectrometry based electronic nose (MS-EN) instrument combined with chemometrics was used to predict the geographical origin of Tempranillo wines produced in Australia and Spain. The MS-EN data generated were analyzed using principal components analysis (PCA), partial least squares discriminant analysis (PLS-DA) and stepwise linear discriminant analysis (SLDA) with full cross validation (leave-one-out method). The SLDA classified correctly 86% of the samples while PLS-DA 85% of Tempranillo wines according to their geographical origin. The relative benefits of using MS-EN will provide capability for rapid screening of wines. However, this technique does not provide the identification and quantitative determination of individual compounds responsible for the different aroma notes in the wine.

  9. Classification of Tempranillo wines according to geographic origin: Combination of mass spectrometry based electronic nose and chemometrics

    International Nuclear Information System (INIS)

    Cynkar, Wies; Dambergs, Robert; Smith, Paul; Cozzolino, Daniel

    2010-01-01

    Rapid methods employing instruments such as electronic noses (EN) or gas sensors are used in the food and beverage industries to monitor and assess the composition and quality of products. Similar to other food industries, the wine industry has a clear need for simple, rapid and cost effective techniques for objectively evaluating the quality of grapes, wine and spirits. In this study a mass spectrometry based electronic nose (MS-EN) instrument combined with chemometrics was used to predict the geographical origin of Tempranillo wines produced in Australia and Spain. The MS-EN data generated were analyzed using principal components analysis (PCA), partial least squares discriminant analysis (PLS-DA) and stepwise linear discriminant analysis (SLDA) with full cross validation (leave-one-out method). The SLDA classified correctly 86% of the samples while PLS-DA 85% of Tempranillo wines according to their geographical origin. The relative benefits of using MS-EN will provide capability for rapid screening of wines. However, this technique does not provide the identification and quantitative determination of individual compounds responsible for the different aroma notes in the wine.

  10. Untargeted mass spectrometry-based metabolomic profiling of pleural effusions: fatty acids as novel cancer biomarkers for malignant pleural effusions.

    Science.gov (United States)

    Lam, Ching-Wan; Law, Chun-Yiu

    2014-09-05

    Untargeted mass spectrometry-based metabolomic profiling is a powerful analytical method used for broad-spectrum identification and quantification of metabolites in biofluids in human health and disease states. In this study, we exploit metabolomic profiling for cancer biomarker discovery for diagnosis of malignant pleural effusions. We envisage the result will be clinically useful since currently there are no cancer biomarkers that are accurate enough for the diagnosis of malignant pleural effusions. Metabolomes of 32 malignant pleural effusions from lung cancer patients and 18 benign effusions from patients with pulmonary tuberculosis were analyzed using reversed-phase liquid chromatography tandem mass spectrometry (LC-MS/MS) using AB SCIEX TripleTOF 5600. MS spectra were analyzed using XCMS, PeakView, and LipidView. Metabolome-Wide Association Study (MWAS) was performed by Receiver Operating Characteristic Curve Explorer and Tester (ROCCET). Insignificant markers were filtered out using a metabolome-wide significance level (MWSL) with p-value pleural effusions. Using a ratio of FFA 18:1-to-ceramide (d18:1/16:0), the area-under-ROC was further increased to 0.99 (95% CI = 0.91-1.00) with sensitivity 93.8% and specificity 100.0%. Using untargeted metabolomic profiling, the diagnostic cancer biomarker with the largest area-under-ROC can be determined objectively. This lipogenic phenotype could be explained by overexpression of fatty acid synthase (FASN) in cancer cells. The diagnostic performance of FFA 18:1-to-ceramide (d18:1/16:0) ratio supports its use for diagnosis of malignant pleural effusions.

  11. Mass spectrometry-based proteomic exploration of the human immune system: focus on the inflammasome, global protein secretion, and T cells.

    Science.gov (United States)

    Nyman, Tuula A; Lorey, Martina B; Cypryk, Wojciech; Matikainen, Sampsa

    2017-05-01

    The immune system is our defense system against microbial infections and tissue injury, and understanding how it works in detail is essential for developing drugs for different diseases. Mass spectrometry-based proteomics can provide in-depth information on the molecular mechanisms involved in immune responses. Areas covered: Summarized are the key immunology findings obtained with MS-based proteomics in the past five years, with a focus on inflammasome activation, global protein secretion, mucosal immunology, immunopeptidome and T cells. Special focus is on extracellular vesicle-mediated protein secretion and its role in immune responses. Expert commentary: Proteomics is an essential part of modern omics-scale immunology research. To date, MS-based proteomics has been used in immunology to study protein expression levels, their subcellular localization, secretion, post-translational modifications, and interactions in immune cells upon activation by different stimuli. These studies have made major contributions to understanding the molecular mechanisms involved in innate and adaptive immune responses. New developments in proteomics offer constantly novel possibilities for exploring the immune system. Examples of these techniques include mass cytometry and different MS-based imaging approaches which can be widely used in immunology.

  12. Adapting mass spectrometry-based platforms for clinical proteomics applications: The capillary electrophoresis coupled mass spectrometry paradigm

    Science.gov (United States)

    Metzger, Jochen; Luppa, Peter B.; Good, David M.; Mischak, Harald

    2018-01-01

    Single biomarker detection is common in clinical laboratories due to the currently available method spectrum. For various diseases, however, no specific single biomarker could be identified. A strategy to overcome this diagnostic void is to shift from single analyte detection to multiplexed biomarker profiling. Mass spectrometric methods were employed for biomarker discovery in body fluids. The enormous complexity of biofluidic proteome compartments implies upstream fractionation. For this reason, mass spectrometry (MS) was coupled to two-dimensional gel electrophoresis, liquid chromatography, surface-enhanced laser desorption/ionization, or capillary electrophoresis (CE). Differences in performance and operating characteristics make them differentially suited for routine laboratory applications. Progress in the field of clinical proteomics relies not only on the use of an adequate technological platform, but also on a fast and efficient proteomic workflow including standardized sample preparation, proteomic data processing, statistical validation of biomarker selection, and sample classification. Based on CE-MS analysis, we describe how proteomic technology can be implemented in a clinical laboratory environment. In the last part of this review, we give an overview of CE-MS-based clinical studies and present information on identity and biological significance of the identified peptide biomarkers providing evidence of disease-induced changes in proteolytic processing and posttranslational modification. PMID:19404829

  13. Sodium laurate, a novel protease- and mass spectrometry-compatible detergent for mass spectrometry-based membrane proteomics.

    Directory of Open Access Journals (Sweden)

    Yong Lin

    Full Text Available The hydrophobic nature of most membrane proteins severely complicates their extraction, proteolysis and identification. Although detergents can be used to enhance the solubility of the membrane proteins, it is often difficult for a detergent not only to have a strong ability to extract membrane proteins, but also to be compatible with the subsequent proteolysis and mass spectrometric analysis. In this study, we made evaluation on a novel application of sodium laurate (SL to the shotgun analysis of membrane proteomes. SL was found not only to lyse the membranes and solubilize membrane proteins as efficiently as SDS, but also to be well compatible with trypsin and chymotrypsin. Furthermore, SL could be efficiently removed by phase transfer method from samples after acidification, thus ensuring not to interfere with the subsequent CapLC-MS/MS analysis of the proteolytic peptides of proteins. When SL was applied to assist the digestion and identification of a standard protein mixture containing bacteriorhodoposin and the proteins in rat liver plasma membrane-enriched fractions, it was found that, compared with other two representative enzyme- and MS-compatible detergents RapiGest SF (RGS and sodium deoxycholate (SDC, SL exhibited obvious superiority in the identification of membrane proteins particularly those with high hydrophobicity and/or multiple transmembrane domains.

  14. Mass spectrometry-based analysis of the HLA-ligandomes of renal cell carcinoma and benign renal tissue

    OpenAIRE

    Rabsteyn, Armin

    2018-01-01

    Peptide vaccination is a promising immunotherapeutic approach for the treatment of malignancies. In this project, the unique opportunity to analyze HLA ligandomes of samples from tumor and adjacent benign tissue of renal cell carcinoma (RCC) patients by mass spectrometry was given. This allowed for the establishment of a novel approach of antigen definition by comparative profiling of malignant and benign HLA ligandomes. Analyses were performed for HLA class I and II of tumor and benign tissu...

  15. Anatomy and evolution of database search engines-a central component of mass spectrometry based proteomic workflows.

    Science.gov (United States)

    Verheggen, Kenneth; Raeder, Helge; Berven, Frode S; Martens, Lennart; Barsnes, Harald; Vaudel, Marc

    2017-09-13

    Sequence database search engines are bioinformatics algorithms that identify peptides from tandem mass spectra using a reference protein sequence database. Two decades of development, notably driven by advances in mass spectrometry, have provided scientists with more than 30 published search engines, each with its own properties. In this review, we present the common paradigm behind the different implementations, and its limitations for modern mass spectrometry datasets. We also detail how the search engines attempt to alleviate these limitations, and provide an overview of the different software frameworks available to the researcher. Finally, we highlight alternative approaches for the identification of proteomic mass spectrometry datasets, either as a replacement for, or as a complement to, sequence database search engines. © 2017 Wiley Periodicals, Inc.

  16. Oxyntomodulin Identified as a Marker of Type 2 Diabetes and Gastric Bypass Surgery by Mass-spectrometry Based Profiling of Human Plasma

    DEFF Research Database (Denmark)

    Wewer Albrechtsen, Nicolai J; Hornburg, Daniel; Albrechtsen, Reidar

    2016-01-01

    applicability of this platform by studying a hitherto neglected glucose- and appetite-regulating gut hormone, namely, oxyntomodulin. Our results show that the secretion of oxyntomodulin in patients with type 2 diabetes is significantly impaired, and that its level is increased by more than 10-fold after gastric......, oxyntomodulin may participate with GLP-1 in the regulation of glucose metabolism and appetite in humans. In conclusion, this mass spectrometry-based platform is a powerful resource for identifying and characterizing metabolically active low-abundance peptides....

  17. Solid-Phase Extraction Strategies to Surmount Body Fluid Sample Complexity in High-Throughput Mass Spectrometry-Based Proteomics

    Science.gov (United States)

    Bladergroen, Marco R.; van der Burgt, Yuri E. M.

    2015-01-01

    For large-scale and standardized applications in mass spectrometry- (MS-) based proteomics automation of each step is essential. Here we present high-throughput sample preparation solutions for balancing the speed of current MS-acquisitions and the time needed for analytical workup of body fluids. The discussed workflows reduce body fluid sample complexity and apply for both bottom-up proteomics experiments and top-down protein characterization approaches. Various sample preparation methods that involve solid-phase extraction (SPE) including affinity enrichment strategies have been automated. Obtained peptide and protein fractions can be mass analyzed by direct infusion into an electrospray ionization (ESI) source or by means of matrix-assisted laser desorption ionization (MALDI) without further need of time-consuming liquid chromatography (LC) separations. PMID:25692071

  18. A Comprehensive Workflow of Mass Spectrometry-Based Untargeted Metabolomics in Cancer Metabolic Biomarker Discovery Using Human Plasma and Urine

    Directory of Open Access Journals (Sweden)

    Jianwen She

    2013-09-01

    Full Text Available Current available biomarkers lack sensitivity and/or specificity for early detection of cancer. To address this challenge, a robust and complete workflow for metabolic profiling and data mining is described in details. Three independent and complementary analytical techniques for metabolic profiling are applied: hydrophilic interaction liquid chromatography (HILIC–LC, reversed-phase liquid chromatography (RP–LC, and gas chromatography (GC. All three techniques are coupled to a mass spectrometer (MS in the full scan acquisition mode, and both unsupervised and supervised methods are used for data mining. The univariate and multivariate feature selection are used to determine subsets of potentially discriminative predictors. These predictors are further identified by obtaining accurate masses and isotopic ratios using selected ion monitoring (SIM and data-dependent MS/MS and/or accurate mass MSn ion tree scans utilizing high resolution MS. A list combining all of the identified potential biomarkers generated from different platforms and algorithms is used for pathway analysis. Such a workflow combining comprehensive metabolic profiling and advanced data mining techniques may provide a powerful approach for metabolic pathway analysis and biomarker discovery in cancer research. Two case studies with previous published data are adapted and included in the context to elucidate the application of the workflow.

  19. Development of an improved high resolution mass spectrometry based multi-residue method for veterinary drugs in various food matrices.

    Science.gov (United States)

    Kaufmann, A; Butcher, P; Maden, K; Walker, S; Widmer, M

    2011-08-26

    Multi-residue methods for veterinary drugs or pesticides in food are increasingly often based on ultra performance liquid chromatography (UPLC) coupled to high resolution mass spectrometry (HRMS). Previous available time of flight (TOF) technologies, showing resolutions up to 15,000 full width at half maximum (FWHM), were not sufficiently selective for monitoring low residue concentrations in difficult matrices (e.g. hormones in tissue or antibiotics in honey). The approach proposed in this paper is based on a single stage Orbitrap mass spectrometer operated at 50,000 FWHM. Extracts (liver and kidney) which were produced according to a validated multi-residue method (time of flight detection based) could not be analyzed by Orbitrap because of extensive signal suppression. This required the improvement of established extraction and clean-up procedures. The introduced, more extensive deproteinzation steps and dedicated instrumental settings successfully eliminated these detrimental suppression effects. The reported method, covering more than 100 different veterinary dugs, was validated according to the EU Commission Decision 2002/657/EEC. Validated matrices include muscle, kidney, liver, fish and honey. Significantly better performance parameters (e.g. linearity, reproducibility and detection limits) were obtained when comparing the new method with the older, TOF based method. These improvements are attributed to the higher resolution (50,000 versus 12,000 FWHM) and the superior mass stability of the of the Orbitrap over the previously utilized TOF instrument. Copyright © 2010 Elsevier B.V. All rights reserved.

  20. Ultra-high performance liquid chromatography coupled with photo-diode array and quadrupole/time-of-flight mass spectrometry based chemical profiling approach to evaluate the influence of preparation methods on the holistic quality of Qiong-Yu-Gao, a traditional complex herbal medicine.

    Science.gov (United States)

    Xu, Jin-Di; Mao, Qian; Shen, Hong; Zhu, Ling-Ying; Li, Song-Lin; Yan, Ru

    2013-08-23

    Qiong-Yu-Gao (QYG), consisting of Rehmanniae Radix (RR), Poriae (PO) and Ginseng Radix (GR), is a commonly used tonic traditional complex herbal medicine (CHM). So far, three different methods have been documented for preparation of QYG, i.e. method 1 (M1): mixing powders of GR and PO with decoction of RR; method 2 (M2): combining the decoction of RR and PO with the decoction of GR; method 3 (M3): decocting the mixture of RR, GR and PO. In present study, an ultra-high performance liquid chromatography coupled with photo-diode array and quadrupole/time-of-flight mass spectrometry (UHPLC-PDA-QTOF-MS/MS) based chemical profiling approach was developed to investigate the influence of the three preparation methods on the holistic quality of QYG. All detected peaks were unambiguously identified by comparing UV spectra, accurate mass data/characteristic mass fragments and retention times with those of reference compounds, and/or tentatively assigned by matching empirical molecular formula with that of known compounds, and/or elucidating quasi-molecular ions and fragment ions referring to information available in literature. A total of 103 components, mainly belonging to ginsenosides, phenethylalcohol glycosides, iridoid glycosides and triterpenoid acids, were identified, of which 5 degraded ginsenosides were putatively determined to be newly generated during preparation procedures of QYG samples. Triterpenoid acids and malonyl-ginsenosides were detected only in M1 samples, while degraded ginsenosides were merely detectable in M2/M3 samples. The possible reasons for the difference among chemical profiles of QYG samples prepared with three methods were also discussed. It could be concluded that preparation method do significantly affect the holistic quality of QYG. The influence of the altered chemical profiles on the bioactivity of QYG needs further investigation. The present study demonstrated that UHPLC-PDA-QTOF-MS/MS based chemical profiling approach is efficient and

  1. Mass Spectrometry-Based Proteomic Profiling of Thrombotic Material Obtained by Endovascular Thrombectomy in Patients with Ischemic Stroke

    Directory of Open Access Journals (Sweden)

    Roberto Muñoz

    2018-02-01

    Full Text Available Thrombotic material retrieved from acute ischemic stroke (AIS patients represents a valuable source of biological information. In this study, we have developed a clinical proteomics workflow to characterize the protein cargo of thrombi derived from AIS patients. To analyze the thrombus proteome in a large-scale format, we developed a workflow that combines the isolation of thrombus by endovascular thrombectomy and peptide chromatographic fractionation coupled to mass-spectrometry. Using this workflow, we have characterized a specific proteomic expression profile derived from four AIS patients included in this study. Around 1600 protein species were unambiguously identified in the analyzed material. Functional bioinformatics analyses were performed, emphasizing a clustering of proteins with immunological functions as well as cardiopathy-related proteins with blood-cell dependent functions and peripheral vascular processes. In addition, we established a reference proteomic fingerprint of 341 proteins commonly detected in all patients. Protein interactome network of this subproteome revealed protein clusters involved in the interaction of fibronectin with 14-3-3 proteins, TGFβ signaling, and TCP complex network. Taken together, our data contributes to the repertoire of the human thrombus proteome, serving as a reference library to increase our knowledge about the molecular basis of thrombus derived from AIS patients, paving the way toward the establishment of a quantitative approach necessary to detect and characterize potential novel biomarkers in the stroke field.

  2. Mass spectrometry-based metabolic profiling of gemcitabine-sensitive and gemcitabine-resistant pancreatic cancer cells.

    Science.gov (United States)

    Fujimura, Yoshinori; Ikenaga, Naoki; Ohuchida, Kenoki; Setoyama, Daiki; Irie, Miho; Miura, Daisuke; Wariishi, Hiroyuki; Murata, Masaharu; Mizumoto, Kazuhiro; Hashizume, Makoto; Tanaka, Masao

    2014-03-01

    Gemcitabine resistance (GR) is one of the critical issues for therapy for pancreatic cancer, but the mechanism still remains unclear. Our aim was to increase the understanding of GR by metabolic profiling approach. To establish GR cells, 2 human pancreatic cancer cell lines, SUIT-2 and CAPAN-1, were exposed to increasing concentration of gemcitabine. Both parental and chemoresistant cells obtained by this treatment were subjected to metabolic profiling based on liquid chromatography-mass spectrometry. Multivariate statistical analyses, both principal component analysis and orthogonal partial least squares discriminant analysis, distinguished metabolic signature of responsiveness and resistance to gemcitabine in both SUIT-2 and CAPAN-1 cells. Among significantly different (P metabolic pathways such as amino acid, nucleotide, energy, cofactor, and vitamin pathways. Decreases in glutamine and proline levels as well as increases in aspartate, hydroxyproline, creatine, and creatinine levels were observed in chemoresistant cells from both cell lines. These results suggest that metabolic profiling can isolate distinct features of pancreatic cancer in the metabolome of gemcitabine-sensitive and GR cells. These findings may contribute to the biomarker discovery and an enhanced understanding of GR in pancreatic cancer.

  3. RNA-Seq and Mass-Spectrometry-Based Lipidomics Reveal Extensive Changes of Glycerolipid Pathways in Brown Adipose Tissue in Response to Cold

    DEFF Research Database (Denmark)

    Marcher, Ann-Britt; Loft, Anne; Nielsen, Ronni

    2015-01-01

    involved in glycerophospholipid synthesis and fatty acid elongation. This is accompanied by significant changes in the acyl chain composition of triacylglycerols (TAGs) as well as subspecies-selective changes of acyl chains in glycerophospholipids. These results indicate that cold adaptation of BAT......Cold exposure greatly alters brown adipose tissue (BAT) gene expression and metabolism to increase thermogenic capacity. Here, we used RNA sequencing and mass-spectrometry-based lipidomics to provide a comprehensive resource describing the molecular signature of cold adaptation at the level...... of the transcriptome and lipidome. We show that short-term (3-day) cold exposure leads to a robust increase in expression of several brown adipocyte genes related to thermogenesis as well as the gene encoding the hormone irisin. However, pathway analysis shows that the most significantly induced genes are those...

  4. Pre-analytic evaluation of volumetric absorptive microsampling and integration in a mass spectrometry-based metabolomics workflow.

    Science.gov (United States)

    Volani, Chiara; Caprioli, Giulia; Calderisi, Giovanni; Sigurdsson, Baldur B; Rainer, Johannes; Gentilini, Ivo; Hicks, Andrew A; Pramstaller, Peter P; Weiss, Guenter; Smarason, Sigurdur V; Paglia, Giuseppe

    2017-10-01

    Volumetric absorptive microsampling (VAMS) is a novel approach that allows single-drop (10 μL) blood collection. Integration of VAMS with mass spectrometry (MS)-based untargeted metabolomics is an attractive solution for both human and animal studies. However, to boost the use of VAMS in metabolomics, key pre-analytical questions need to be addressed. Therefore, in this work, we integrated VAMS in a MS-based untargeted metabolomics workflow and investigated pre-analytical strategies such as sample extraction procedures and metabolome stability at different storage conditions. We first evaluated the best extraction procedure for the polar metabolome and found that the highest number and amount of metabolites were recovered upon extraction with acetonitrile/water (70:30). In contrast, basic conditions (pH 9) resulted in divergent metabolite profiles mainly resulting from the extraction of intracellular metabolites originating from red blood cells. In addition, the prolonged storage of blood samples at room temperature caused significant changes in metabolome composition, but once the VAMS devices were stored at - 80 °C, the metabolome remained stable for up to 6 months. The time used for drying the sample did also affect the metabolome. In fact, some metabolites were rapidly degraded or accumulated in the sample during the first 48 h at room temperature, indicating that a longer drying step will significantly change the concentration in the sample. Graphical abstract Volumetric absorptive microsampling (VAMS) is a novel technology that allows single-drop blood collection and, in combination with mass spectrometry (MS)-based untargeted metabolomics, represents an attractive solution for both human and animal studies. In this work, we integrated VAMS in a MS-based untargeted metabolomics workflow and investigated pre-analytical strategies such as sample extraction procedures and metabolome stability at different storage conditions. The latter revealed that

  5. High-performance liquid chromatography-mass spectrometry-based acetylcholinesterase assay for the screening of inhibitors in natural extracts

    NARCIS (Netherlands)

    de Jong, C.F.; Derks, R.J.E.; Bruyneel, B.; Niessen, W.M.A.; Irth, H.

    2006-01-01

    The present paper describes a High-performance liquid chromatography-mass spectrometry (LC-MS) methodology for the screening of acetylcholinesterase (AChE) inhibitors in natural extracts. AChE activity of sample components is monitored by a post-column biochemical assay that is based on the

  6. Combined experimental and statistical strategy for mass spectrometry based serum protein profiling for diagnosis of breast cancer

    DEFF Research Database (Denmark)

    Callesen, Anne Kjærgaard; Vach, Werner; Jørgensen, Per E

    2008-01-01

    it in a well-described breast cancer case-control study. A rigorous sample collection protocol ensured high quality specimen and reduced bias from preanalytical factors. Preoperative serum samples obtained from 48 breast cancer patients and 28 controls were used to generate MALDI MS protein profiles. A total...... and controls. A diagnostic rule based on these 72 mass values was constructed and exhibited a cross-validated sensitivity and specificity of approximately 85% for the detection of breast cancer. With this method, it was possible to distinguish early stage cancers from controls without major loss of sensitivity...... and specificity. We conclude that optimized serum sample handling and mass spectrometry data acquisition strategies in combination with statistical analysis provide a viable platform for serum protein profiling in cancer diagnosis....

  7. A Quantitative Tool to Distinguish Isobaric Leucine and Isoleucine Residues for Mass Spectrometry-Based De Novo Monoclonal Antibody Sequencing

    Science.gov (United States)

    Poston, Chloe N.; Higgs, Richard E.; You, Jinsam; Gelfanova, Valentina; Hale, John E.; Knierman, Michael D.; Siegel, Robert; Gutierrez, Jesus A.

    2014-07-01

    De novo sequencing by mass spectrometry (MS) allows for the determination of the complete amino acid (AA) sequence of a given protein based on the mass difference of detected ions from MS/MS fragmentation spectra. The technique relies on obtaining specific masses that can be attributed to characteristic theoretical masses of AAs. A major limitation of de novo sequencing by MS is the inability to distinguish between the isobaric residues leucine (Leu) and isoleucine (Ile). Incorrect identification of Ile as Leu or vice versa often results in loss of activity in recombinant antibodies. This functional ambiguity is commonly resolved with costly and time-consuming AA mutation and peptide sequencing experiments. Here, we describe a set of orthogonal biochemical protocols, which experimentally determine the identity of Ile or Leu residues in monoclonal antibodies (mAb) based on the selectivity that leucine aminopeptidase shows for n-terminal Leu residues and the cleavage preference for Leu by chymotrypsin. The resulting observations are combined with germline frequencies and incorporated into a logistic regression model, called Predictor for Xle Sites (PXleS) to provide a statistical likelihood for the identity of Leu at an ambiguous site. We demonstrate that PXleS can generate a probability for an Xle site in mAbs with 96% accuracy. The implementation of PXleS precludes the expression of several possible sequences and, therefore, reduces the overall time and resources required to go from spectra generation to a biologically active sequence for a mAb when an Ile or Leu residue is in question.

  8. Newborn screening by matrix-assisted laser desorption/ionization mass spectrometry based on parylene-matrix chip.

    Science.gov (United States)

    Kim, Jo-Il; Noh, Joo-Yoon; Kim, Mira; Park, Jong-Min; Song, Hyun-Woo; Kang, Min-Jung; Pyun, Jae-Chul

    2017-08-01

    Newborn screening for diagnosis of phenylketonuria, homocystinuria, and maple syrup urine disease have been conducted by analyzing the concentration of target amino acids using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-ToF MS) based on parylene-matrix chip. Parylene-matrix chip was applied to MALDI-ToF MS analysis reducing the matrix peaks significantly at low mass-to-charge ratio range (m/z  0.98) and the LODs were ranging from 9.0 to 22.9 μg/mL. Effect of proteins in serum was estimated by comparing MALDI-ToF mass spectra of amino acids-spiked serum before and after the methanol extraction. Interference of other amino acids on analysis of target analyte was determined to be insignificant. From these results, MALDI-ToF MS based on parylene-matrix chip could be applicable to medical diagnosis of neonatal metabolic disorders. Copyright © 2017 Elsevier Inc. All rights reserved.

  9. An analytical platform for mass spectrometry-based identification and chemical analysis of RNA in ribonucleoprotein complexes.

    Science.gov (United States)

    Taoka, Masato; Yamauchi, Yoshio; Nobe, Yuko; Masaki, Shunpei; Nakayama, Hiroshi; Ishikawa, Hideaki; Takahashi, Nobuhiro; Isobe, Toshiaki

    2009-11-01

    We describe here a mass spectrometry (MS)-based analytical platform of RNA, which combines direct nano-flow reversed-phase liquid chromatography (RPLC) on a spray tip column and a high-resolution LTQ-Orbitrap mass spectrometer. Operating RPLC under a very low flow rate with volatile solvents and MS in the negative mode, we could estimate highly accurate mass values sufficient to predict the nucleotide composition of a approximately 21-nucleotide small interfering RNA, detect post-transcriptional modifications in yeast tRNA, and perform collision-induced dissociation/tandem MS-based structural analysis of nucleolytic fragments of RNA at a sub-femtomole level. Importantly, the method allowed the identification and chemical analysis of small RNAs in ribonucleoprotein (RNP) complex, such as the pre-spliceosomal RNP complex, which was pulled down from cultured cells with a tagged protein cofactor as bait. We have recently developed a unique genome-oriented database search engine, Ariadne, which allows tandem MS-based identification of RNAs in biological samples. Thus, the method presented here has broad potential for automated analysis of RNA; it complements conventional molecular biology-based techniques and is particularly suited for simultaneous analysis of the composition, structure, interaction, and dynamics of RNA and protein components in various cellular RNP complexes.

  10. An update on MALDI mass spectrometry based technology for the analysis of fingermarks - stepping into operational deployment.

    Science.gov (United States)

    Francese, S; Bradshaw, R; Denison, N

    2017-07-10

    Since 2009, when Matrix Assisted Laser Desorption Ionisation Mass Spectrometry Imaging (MALDI MSI) was firstly reported for the molecular mapping of latent fingermarks, the range of information and operational capabilities have steadily increased. Pioneering work from our Fingermark Research Group exploited different modalities, including Profiling (MALDI MSP), tandem mass spectrometry (MS/MS) and Ion Mobility MS/MS; a number of methodologies were also developed to conquer a main challenge, namely profiling the suspect and their actions prior to or whilst committing the crime. Suspect profiling here is no longer based on behavioural science but complements this discipline and the investigations by detecting and visualising the molecular make-up of fingermarks onto the identifying ridges. This forensic opportunity provides the link between the biometric information (ridge detail) and the corpus delicti or intelligence on the circumstances of the crime. In 2013, a review was published covering the research work and developments of four years supported by the Home Office, UK, and the local regional Police with some insights (and comparison) into similar research being reported employing other mass spectrometric techniques. The present review is an extensive update on the MALDI MS based methods' achievements, limitations and work in progress in fingermark analysis; it also offers an outlook on further necessary research into this subject. The main highlights are the increased number of possible information retrievable around a suspect and the more extended compatibility of this technology. The latter has allowed MALDI MS based methods to integrate well with current forensic fingerprinting, leading to the investigation of real police casework.

  11. Influences of Normalization Method on Biomarker Discovery in Gas Chromatography-Mass Spectrometry-Based Untargeted Metabolomics: What Should Be Considered?

    Science.gov (United States)

    Chen, Jiaqing; Zhang, Pei; Lv, Mengying; Guo, Huimin; Huang, Yin; Zhang, Zunjian; Xu, Fengguo

    2017-05-16

    Data reduction techniques in gas chromatography-mass spectrometry-based untargeted metabolomics has made the following workflow of data analysis more lucid. However, the normalization process still perplexes researchers, and its effects are always ignored. In order to reveal the influences of normalization method, five representative normalization methods (mass spectrometry total useful signal, median, probabilistic quotient normalization, remove unwanted variation-random, and systematic ratio normalization) were compared in three real data sets with different types. First, data reduction techniques were used to refine the original data. Then, quality control samples and relative log abundance plots were utilized to evaluate the unwanted variations and the efficiencies of normalization process. Furthermore, the potential biomarkers which were screened out by the Mann-Whitney U test, receiver operating characteristic curve analysis, random forest, and feature selection algorithm Boruta in different normalized data sets were compared. The results indicated the determination of the normalization method was difficult because the commonly accepted rules were easy to fulfill but different normalization methods had unforeseen influences on both the kind and number of potential biomarkers. Lastly, an integrated strategy for normalization method selection was recommended.

  12. False-Positive Rate Determination of Protein Target Discovery using a Covalent Modification- and Mass Spectrometry-Based Proteomics Platform

    Science.gov (United States)

    Strickland, Erin C.; Geer, M. Ariel; Hong, Jiyong; Fitzgerald, Michael C.

    2014-01-01

    Detection and quantitation of protein-ligand binding interactions is important in many areas of biological research. Stability of proteins from rates of oxidation (SPROX) is an energetics-based technique for identifying the proteins targets of ligands in complex biological mixtures. Knowing the false-positive rate of protein target discovery in proteome-wide SPROX experiments is important for the correct interpretation of results. Reported here are the results of a control SPROX experiment in which chemical denaturation data is obtained on the proteins in two samples that originated from the same yeast lysate, as would be done in a typical SPROX experiment except that one sample would be spiked with the test ligand. False-positive rates of 1.2-2.2 % and analysis of the isobaric mass tag (e.g., iTRAQ®) reporter ions used for peptide quantitation. Our results also suggest that technical replicates can be used to effectively eliminate such false positives that result from this random error, as is demonstrated in a SPROX experiment to identify yeast protein targets of the drug, manassantin A. The impact of ion purity in the tandem mass spectral analyses and of background oxidation on the false-positive rate of protein target discovery using SPROX is also discussed.

  13. Paper Spray Tandem Mass Spectrometry Based on Molecularly Imprinted Polymer Substrate for Cocaine Analysis in Oral Fluid

    Science.gov (United States)

    Tavares, Ludmyla S.; Carvalho, Thays C.; Romão, Wanderson; Vaz, Boniek G.; Chaves, Andréa R.

    2018-03-01

    This study proposes a new direct and fast method of analysis employing paper spray mass spectrometry (PS-MS). The paper used in the proposed method was modified with molecularly imprinted polymers (MIP) to create a specific site for cocaine analysis in oral fluid. MIP membrane was successfully synthetized and employed. The developed method showed to be linear in a concentration range from LOQ to 100 ng mL-1. The experimental value of LOQ obtained was 1 ng mL-1. The inter-day and intra-day precision and accuracy of the PS-MS method presented values lower than 15%. The total recoveries were also evaluated. The PS-MS method for the analysis of cocaine in oral fluid showed to be very promising and the validation parameters showed a good correlation with the literature. [Figure not available: see fulltext.

  14. Mass spectrometry based biomarker discovery, verification, and validation--quality assurance and control of protein biomarker assays.

    Science.gov (United States)

    Parker, Carol E; Borchers, Christoph H

    2014-06-01

    In its early years, mass spectrometry (MS)-based proteomics focused on the cataloging of proteins found in different species or different tissues. By 2005, proteomics was being used for protein quantitation, typically based on "proteotypic" peptides which act as surrogates for the parent proteins. Biomarker discovery is usually done by non-targeted "shotgun" proteomics, using relative quantitation methods to determine protein expression changes that correlate with disease (output given as "up-or-down regulation" or "fold-increases"). MS-based techniques can also perform "absolute" quantitation which is required for clinical applications (output given as protein concentrations). Here we describe the differences between these methods, factors that affect the precision and accuracy of the results, and some examples of recent studies using MS-based proteomics to verify cancer-related biomarkers. Copyright © 2014 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

  15. Trace isotope analysis using resonance ionization mass spectrometry based on isotope selection with doppler shift of laser ablated atoms

    International Nuclear Information System (INIS)

    Higuchi, Yuki; Watanabe, Kenichi; Kawarabayashi, Jun; Iguchi, Tetsuo

    2005-01-01

    We have proposed a novel isotope selective Resonance Ionization Mass Spectroscopy (RIMS) concept, which can avoid the Doppler broadening on solid sample direct measurement based on laser ablation technique. We have succeeded in experimentally demonstrating the principle of our RIMS concept. Through comparison between the simulated and experimental results, we have validated the simulation model. It would be concluded from these results that we could achieve the isotope selectivity defined as the ratio of 41 Ca to 40 Ca sensitivity to be 4.5x10 10 by adopting the multi-step excitation scheme in the present method. As future works, we will try to experimentally perform the multi-step excitation scheme and improve the detection efficiency by modifying the ion extraction configuration. (author)

  16. Evaluation of matrix effect in isotope dilution mass spectrometry based on quantitative analysis of chloramphenicol residues in milk powder

    International Nuclear Information System (INIS)

    Li, Xiu Qin; Yang, Zong; Zhang, Qing He; Li, Hong Mei

    2014-01-01

    Graphical abstract: -- Highlights: •We develop a strategy to evaluate matrix effect and its impact on the IDMS results. •Matrix effect and IDMS correction factor from different conditions are evaluated. •Ion suppression effect is observed in LLE and HLB pre-treated sample solutions. •Ion enhancement effect is found in MCX pre-treated sample solution. •IDMS correction factor in HLB and MCX solutions in three instruments is close to 1 -- Abstract: In the present study, we developed a comprehensive strategy to evaluate matrix effect (ME) and its impact on the results of isotope dilution mass spectrometry (IDMS) in analysis of chloramphenicol (CAP) residues in milk powder. Stable isotope-labeled internal standards do not always compensate ME, which brings the variation of the ratio (the peak area of analyte/the peak area of isotope). In our investigation, impact factors of this variation were studied in the extraction solution of milk powder using three mass spectrometers coupled with different ion source designs, and deuterium-labeled chloramphenicol (D5-CAP) was used as the internal standard. ME from mobile phases, sample solvents, pre-treatment methods, sample origins and instruments was evaluated, and its impact on the results of IDMS was assessed using the IDMS correction factor (θ). Our data showed that the impact of ME of mobile phase on the correction factor was significantly greater than that of sample solvent. Significant ion suppression and enhancement effects were observed in different pre-treated sample solutions. The IDMS correction factor in liquid–liquid extraction (LLE) and molecular imprinted polymer (MIP) extract with different instruments was greater or less 1.0, and the IDMS correction factor in hydrophilic lipophilic balance (HLB) and mix-mode cation exchange (MCX) extract with different instruments was all close to 1.0. To the instrument coupled with different ion source design, the impact of ME on IDMS quantitative results was

  17. Tandem mass spectrometry-based newborn screening strategy could be used to facilitate rapid and sensitive lung cancer diagnosis

    Directory of Open Access Journals (Sweden)

    Huang T

    2016-04-01

    Full Text Available Ting Huang,1,* Yunfeng Cao,1,* Jia Zeng,1 Jun Dong,2 Xiaoyu Sun,2 Jianxing Chen,1 Peng Gao2,3 1Key Laboratory of Contraceptives and Devices Research (NPFPC, Shanghai Engineer and Technology Research Center of Reproductive Health Drug and Devices, Shanghai Institute of Planned Parenthood Research, Shanghai, 2Clinical Laboratory, Dalian Sixth People’s Hospital, 3CASKey Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, People’s Republic of China *These authors contributed equally to this work Objective: Newborn screening (NBS helps in the early detection of inborn errors of metabolism (IEM. The most effective NBS strategy prevailing in clinics is tandem mass spectrometry (MS/MS analysis using dried blood spot (DBS samples. Taking lung cancer (LC as an example, this study tried to explore if this technique could be of any assistance for the discovery of tumor metabolite markers.Materials and methods: Twenty-six acylcarnitines and 23 amino acids, which are commonly used in IEM screening, were quantified using DBS samples from 222 LC patients, 118 benign lung disease (LD patients, and 96 healthy volunteers (CONT. Forty-four calculated ratios based on the abovementioned metabolites were also included using MS/MS quantification results.Results: This pilot study led to the findings of 65 significantly changed amino acids, acylcarnitines, and some of their ratios for the LC, LD, and CONT groups. Among the differential parameters, 12 items showed reverse changing trends between the LC and LD groups compared to the CONT group. Regression analysis demonstrated that six of them – Arg, Pro, C10:1, Arg/Orn, Cit/Arg, and C5-OH/C0 – could be used to diagnose LC with a sensitivity of 91.3% and a specificity of 92.7%.Conclusion: This study demonstrated the DBS-based MS/MS strategy was a promising tool for the discovery of tumor metabolite markers. Remarkably, this MS

  18. Investigation of Pokemon-regulated proteins in hepatocellular carcinoma using mass spectrometry-based multiplex quantitative proteomics.

    Science.gov (United States)

    Bi, Xin; Jin, Yibao; Gao, Xiang; Liu, Feng; Gao, Dan; Jiang, Yuyang; Liu, Hongxia

    2013-01-01

    Pokemon is a transcription regulator involved in embryonic development, cellular differentiation and oncogenesis. It is aberrantly overexpressed in multiple human cancers including Hepatocellular carcinoma (HCC) and is considered as a promising biomarker for HCC. In this work, the isobaric tags for relative and absolute quantitation (iTRAQ)-based quantitative proteomics strategy was used to investigate the proteomic profile associated with Pokemon in human HCC cell line QGY7703 and human hepatocyte line HL7702. Samples were labeled with four-plex iTRAQ reagents followed by two-dimensional liquid chromatography coupled with tandem mass spectrometry analysis. A total of 24 differentially expressed proteins were selected as significant. Nine proteins were potentially up-regulated by Pokemon while 15 proteins were potentially down-regulated and many proteins were previously identified as potential biomarkers for HCC. Gene ontology (GO) term enrichment revealed that the listed proteins were mainly involved in DNA metabolism and biosynthesis process. The changes of glucose-6-phosphate 1-dehydrogenase (G6PD, up-regulated) and ribonucleoside-diphosphate reductase large sub-unit (RIM1, down-regulated) were validated by Western blotting analysis and denoted as Pokemon's function of oncogenesis. We also found that Pokemon potentially repressed the expression of highly clustered proteins (MCM3, MCM5, MCM6, MCM7) which played key roles in promoting DNA replication. Altogether, our results may help better understand the role of Pokemon in HCC and promote the clinical applications.

  19. Mass spectrometry-based phytochemical screening for hypoglycemic activity of Fagioli di Sarconi beans (Phaseolus vulgaris L.).

    Science.gov (United States)

    Pascale, Raffaella; Bianco, Giuliana; Cataldi, Tommaso R I; Kopplin, Philippe-Schmitt; Bosco, Federica; Vignola, Lisiana; Uhl, Jenny; Lucio, Marianna; Milella, Luigi

    2018-03-01

    The present study deals with the evaluation of antidiabetic activities of Fagioli di Sarconi beans (Phaseolus vulgaris), including 21 ecotypes protected by the European Union with the mark PGI (i.e., Protected Geographical Indication), and cultivated in Basilicata (southern Italy). For this purpose, α-glucosidase and α-amylase assays were assessed; among all bean ecotypes, the tight green seed colour of Verdolino extracts exhibited the highest α-glucosidase and α-amylase inhibitory activity with IC 50 =1.1±0.1μg/ml and IC 50 =19.3±1.1μg/ml, respectively. Phytochemical compound screening of all Fagioli di Sarconi beans performed by flow injection-electrospray ionization-ultrahigh resolution mass spectrometry (uHRMS) and based on the calculation of elemental formulas from accurate m/z values, was helpful to annotate specific compounds, such as alkaloids, saponins, flavonoids, and terpenoids, which are most likely responsible for their biological activity. Copyright © 2017. Published by Elsevier Ltd.

  20. Selecting Sample Preparation Workflows for Mass Spectrometry-Based Proteomic and Phosphoproteomic Analysis of Patient Samples with Acute Myeloid Leukemia.

    Science.gov (United States)

    Hernandez-Valladares, Maria; Aasebø, Elise; Selheim, Frode; Berven, Frode S; Bruserud, Øystein

    2016-08-22

    Global mass spectrometry (MS)-based proteomic and phosphoproteomic studies of acute myeloid leukemia (AML) biomarkers represent a powerful strategy to identify and confirm proteins and their phosphorylated modifications that could be applied in diagnosis and prognosis, as a support for individual treatment regimens and selection of patients for bone marrow transplant. MS-based studies require optimal and reproducible workflows that allow a satisfactory coverage of the proteome and its modifications. Preparation of samples for global MS analysis is a crucial step and it usually requires method testing, tuning and optimization. Different proteomic workflows that have been used to prepare AML patient samples for global MS analysis usually include a standard protein in-solution digestion procedure with a urea-based lysis buffer. The enrichment of phosphopeptides from AML patient samples has previously been carried out either with immobilized metal affinity chromatography (IMAC) or metal oxide affinity chromatography (MOAC). We have recently tested several methods of sample preparation for MS analysis of the AML proteome and phosphoproteome and introduced filter-aided sample preparation (FASP) as a superior methodology for the sensitive and reproducible generation of peptides from patient samples. FASP-prepared peptides can be further fractionated or IMAC-enriched for proteome or phosphoproteome analyses. Herein, we will review both in-solution and FASP-based sample preparation workflows and encourage the use of the latter for the highest protein and phosphorylation coverage and reproducibility.

  1. Selecting Sample Preparation Workflows for Mass Spectrometry-Based Proteomic and Phosphoproteomic Analysis of Patient Samples with Acute Myeloid Leukemia

    Directory of Open Access Journals (Sweden)

    Maria Hernandez-Valladares

    2016-08-01

    Full Text Available Global mass spectrometry (MS-based proteomic and phosphoproteomic studies of acute myeloid leukemia (AML biomarkers represent a powerful strategy to identify and confirm proteins and their phosphorylated modifications that could be applied in diagnosis and prognosis, as a support for individual treatment regimens and selection of patients for bone marrow transplant. MS-based studies require optimal and reproducible workflows that allow a satisfactory coverage of the proteome and its modifications. Preparation of samples for global MS analysis is a crucial step and it usually requires method testing, tuning and optimization. Different proteomic workflows that have been used to prepare AML patient samples for global MS analysis usually include a standard protein in-solution digestion procedure with a urea-based lysis buffer. The enrichment of phosphopeptides from AML patient samples has previously been carried out either with immobilized metal affinity chromatography (IMAC or metal oxide affinity chromatography (MOAC. We have recently tested several methods of sample preparation for MS analysis of the AML proteome and phosphoproteome and introduced filter-aided sample preparation (FASP as a superior methodology for the sensitive and reproducible generation of peptides from patient samples. FASP-prepared peptides can be further fractionated or IMAC-enriched for proteome or phosphoproteome analyses. Herein, we will review both in-solution and FASP-based sample preparation workflows and encourage the use of the latter for the highest protein and phosphorylation coverage and reproducibility.

  2. A rapid liquid chromatography tandem mass spectrometry-based method for measuring propranolol on dried blood spots.

    Science.gov (United States)

    Della Bona, Maria Luisa; Malvagia, Sabrina; Villanelli, Fabio; Giocaliere, Elisa; Ombrone, Daniela; Funghini, Silvia; Filippi, Luca; Cavallaro, Giacomo; Bagnoli, Paola; Guerrini, Renzo; la Marca, Giancarlo

    2013-05-05

    Propranolol, a non-selective beta blocker drug, is used in young infants and newborns for treating several heart diseases; its pharmacokinetics has been extensively evaluated in adult patients using extrapolation to treat pediatric population. The purpose of the present study was to develop and validate a method to measure propranolol levels in dried blood spots. The analysis was performed by using liquid chromatography/tandem mass spectrometry operating in multiple reaction monitoring mode. The calibration curve in matrix was linear in the concentration range of 2.5-200 μg/L with correlation coefficient r=0.9996. Intra-day and inter-day precisions and biases were less than 8.0% (n=10) and 11.5% (n=10) respectively. The recoveries ranged from 94 to 100% and the matrix effect did not result in a severe signal suppression. Propranolol on dried blood spot showed a good stability at three different temperatures for one month. This paper describes a micromethod for measuring propranolol levels on dried blood spot, which determines a great advantage in neonates or young infants during pharmacokinetic studies because of less invasive sampling and small blood volume required. Copyright © 2013 Elsevier B.V. All rights reserved.

  3. Combined Mass Spectrometry-Based Metabolite Profiling of Different Pigmented Rice (Oryza sativa L. Seeds and Correlation with Antioxidant Activities

    Directory of Open Access Journals (Sweden)

    Ga Ryun Kim

    2014-09-01

    Full Text Available Nine varieties of pigmented rice (Oryza sativa L. seeds that were black, red, or white were used to perform metabolite profiling by using ultra-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry (UPLC-Q-TOF-MS and gas chromatography (GC TOF-MS, to measure antioxidant activities. Clear grouping patterns determined by the color of the rice seeds were identified in principle component analysis (PCA derived from UPLC-Q-TOF-MS. Cyanidin-3-glucoside, peonidin-3-glucoside, proanthocyanidin dimer, proanthocyanidin trimer, apigenin-6-C-glugosyl-8-C-arabiboside, tricin-O-rhamnoside-O-hexoside, and lipids were identified as significantly different secondary metabolites. In PCA score plots derived from GC-TOF-MS, Jakwangdo (JKD and Ilpoom (IP species were discriminated from the other rice seeds by PC1 and PC2. Valine, phenylalanine, adenosine, pyruvate, nicotinic acid, succinic acid, maleic acid, malonic acid, gluconic acid, xylose, fructose, glucose, maltose, and myo-inositol were significantly different primary metabolites in JKD species, while GABA, asparagine, xylitol, and sucrose were significantly distributed in IP species. Analysis of antioxidant activities revealed that black and red rice seeds had higher activity than white rice seeds. Cyanidin-3-glucoside, peonidin-3-glucoside, proanthocyanidin dimers, proanthocyanidin trimers, and catechin were highly correlated with antioxidant activities, and were more plentiful in black and red rice seeds. These results are expected to provide valuable information that could help improve and develop rice-breeding techniques.

  4. Mass spectrometry-based cDNA profiling as a potential tool for human body fluid identification.

    Science.gov (United States)

    Donfack, Joseph; Wiley, Anissa

    2015-05-01

    Several mRNA markers have been exhaustively evaluated for the identification of human venous blood, saliva, and semen in forensic genetics. As new candidate human body fluid specific markers are discovered, evaluated, and reported in the scientific literature, there is an increasing trend toward determining the ideal markers for cDNA profiling of body fluids of forensic interest. However, it has not been determined which molecular genetics-based technique(s) should be utilized to assess the performance of these markers. In recent years, only a few confirmatory, mRNA/cDNA-based methods have been evaluated for applications in body fluid identification. The most frequently described methods tested to date include quantitative polymerase chain reaction (qPCR) and capillary electrophoresis (CE). However these methods, in particular qPCR, often favor narrow multiplex PCR due to the availability of a limited number of fluorescent dyes/tags. In an attempt to address this technological constraint, this study explored matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF MS) for human body fluid identification via cDNA profiling of venous blood, saliva, and semen. Using cDNA samples at 20pg input phosphoglycerate kinase 1 (PGK1) amounts, body fluid specific markers for the candidate genes were amplified in their corresponding body fluid (i.e., venous blood, saliva, or semen) and absent in the remaining two (100% specificity). The results of this study provide an initial indication that MALDI-TOF MS is a potential fluorescent dye-free alternative method for body fluid identification in forensic casework. However, the inherent issues of low amounts of mRNA, and the damage caused to mRNA by environmental exposures, extraction processes, and storage conditions are important factors that significantly hinder the implementation of cDNA profiling into forensic casework. Published by Elsevier Ireland Ltd.

  5. QC-ART: A tool for real-time quality control assessment of mass spectrometry-based proteomics data.

    Science.gov (United States)

    Stanfill, Bryan A; Nakayasu, Ernesto S; Bramer, Lisa M; Thompson, Allison M; Ansong, Charles K; Clauss, Therese; Gritsenko, Marina A; Monroe, Matthew E; Moore, Ronald J; Orton, Daniel J; Piehowski, Paul D; Schepmoes, Athena A; Smith, Richard D; Webb-Robertson, Bobbie-Jo; Metz, Thomas O; TEDDY Study Group, The Environmental Determinants Of Diabetes In The Young

    2018-04-17

    Liquid chromatography-mass spectrometry (LC-MS)-based proteomics studies of large sample cohorts can easily require from months to years to complete. Acquiring consistent, high-quality data in such large-scale studies is challenging because of normal variations in instrumentation performance over time, as well as artifacts introduced by the samples themselves, such as those due to collection, storage and processing. Existing quality control methods for proteomics data primarily focus on post-hoc analysis to remove low-quality data that would degrade downstream statistics; they are not designed to evaluate the data in near real-time, which would allow for interventions as soon as deviations in data quality are detected.  In addition to flagging analyses that demonstrate outlier behavior, evaluating how the data structure changes over time can aide in understanding typical instrument performance or identify issues such as a degradation in data quality due to the need for instrument cleaning and/or re-calibration.  To address this gap for proteomics, we developed Quality Control Analysis in Real-Time (QC-ART), a tool for evaluating data as they are acquired in order to dynamically flag potential issues with instrument performance or sample quality.  QC-ART has similar accuracy as standard post-hoc analysis methods with the additional benefit of real-time analysis.  We demonstrate the utility and performance of QC-ART in identifying deviations in data quality due to both instrument and sample issues in near real-time for LC-MS-based plasma proteomics analyses of a sample subset of The Environmental Determinants of Diabetes in the Young cohort. We also present a case where QC-ART facilitated the identification of oxidative modifications, which are often underappreciated in proteomic experiments. Published under license by The American Society for Biochemistry and Molecular Biology, Inc.

  6. UV irradiation-induced methionine oxidation in human skin keratins: Mass spectrometry-based non-invasive proteomic analysis.

    Science.gov (United States)

    Lee, Seon Hwa; Matsushima, Keita; Miyamoto, Kohei; Oe, Tomoyuki

    2016-02-05

    Ultraviolet (UV) radiation is the major environmental factor that causes oxidative skin damage. Keratins are the main constituents of human skin and have been identified as oxidative target proteins. We have recently developed a mass spectrometry (MS)-based non-invasive proteomic methodology to screen oxidative modifications in human skin keratins. Using this methodology, UV effects on methionine (Met) oxidation in human skin keratins were investigated. The initial screening revealed that Met(259), Met(262), and Met(296) in K1 keratin were the most susceptible oxidation sites upon UVA (or UVB) irradiation of human tape-stripped skin. Subsequent liquid chromatography/electrospray ionization-MS and tandem MS analyses confirmed amino acid sequences and oxidation sites of tryptic peptides D(290)VDGAYMTK(298) (P1) and N(258)MQDMVEDYR(267) (P2). The relative oxidation levels of P1 and P2 increased in a time-dependent manner upon UVA irradiation. Butylated hydroxytoluene was the most effective antioxidant for artifactual oxidation of Met residues. The relative oxidation levels of P1 and P2 after UVA irradiation for 48 h corresponded to treatment with 100mM hydrogen peroxide for 15 min. In addition, Met(259) was oxidized by only UVA irradiation. The Met sites identified in conjunction with the current proteomic methodology can be used to evaluate skin damage under various conditions of oxidative stress. We demonstrated that the relative Met oxidation levels in keratins directly reflected UV-induced damages to human tape-stripped skin. Human skin proteins isolated by tape stripping were analyzed by MS-based non-invasive proteomic methodology. Met(259), Met(262), and Met(296) in K1 keratin were the most susceptible oxidation sites upon UV irradiation. Met(259) was oxidized by only UVA irradiation. Quantitative LC/ESI-SRM/MS analyses confirmed a time-dependent increase in the relative oxidation of target peptides (P1 and P2) containing these Met residues, upon UVA irradiation

  7. Combination of mass spectrometry-based targeted lipidomics and supervised machine learning algorithms in detecting adulterated admixtures of white rice.

    Science.gov (United States)

    Lim, Dong Kyu; Long, Nguyen Phuoc; Mo, Changyeun; Dong, Ziyuan; Cui, Lingmei; Kim, Giyoung; Kwon, Sung Won

    2017-10-01

    The mixing of extraneous ingredients with original products is a common adulteration practice in food and herbal medicines. In particular, authenticity of white rice and its corresponding blended products has become a key issue in food industry. Accordingly, our current study aimed to develop and evaluate a novel discrimination method by combining targeted lipidomics with powerful supervised learning methods, and eventually introduce a platform to verify the authenticity of white rice. A total of 30 cultivars were collected, and 330 representative samples of white rice from Korea and China as well as seven mixing ratios were examined. Random forests (RF), support vector machines (SVM) with a radial basis function kernel, C5.0, model averaged neural network, and k-nearest neighbor classifiers were used for the classification. We achieved desired results, and the classifiers effectively differentiated white rice from Korea to blended samples with high prediction accuracy for the contamination ratio as low as five percent. In addition, RF and SVM classifiers were generally superior to and more robust than the other techniques. Our approach demonstrated that the relative differences in lysoGPLs can be successfully utilized to detect the adulterated mixing of white rice originating from different countries. In conclusion, the present study introduces a novel and high-throughput platform that can be applied to authenticate adulterated admixtures from original white rice samples. Copyright © 2017 Elsevier Ltd. All rights reserved.

  8. Mass spectrometry based approach for identification and characterisation of fluorescent proteins from marine organisms

    DEFF Research Database (Denmark)

    Wojdyla, Katarzyna Iwona; Rogowska-Wrzesinska, Adelina; Wrzesinski, Krzysztof

    2011-01-01

    We present here a new analytical strategy for identification and characterisation of fluorescent proteins from marine organisms. By applying basic proteomics tools it is possible to screen large sample collections for fluorescent proteins of desired characteristics prior to gene cloning. Our...

  9. A stable-isotope mass spectrometry-based metabolic footprinting approach to analyze exudates from phytoplankton

    DEFF Research Database (Denmark)

    Weber, Ralf J. M.; Selander, Erik; Sommer, Ulf

    2013-01-01

    Phytoplankton exudates play an important role in pelagic ecology and biogeochemical cycles of elements. Exuded compounds fuel the microbial food web and often encompass bioactive secondary metabolites like sex pheromones, allelochemicals, antibiotics, or feeding attractants that mediate biological...... interactions. Despite this importance, little is known about the bioactive compounds present in phytoplankton exudates. We report a stable-isotope metabolic footprinting method to characterise exudates from aquatic autotrophs. Exudates from 13C-enriched alga were concentrated by solid phase extraction...

  10. Biochemical and Mass Spectrometry-Based Approaches to Profile SUMOylation in Human Cells

    DEFF Research Database (Denmark)

    Kessler, Benedikt M; Bursomanno, Sara; McGouran, Joanna F

    2017-01-01

    Posttranslational modification of proteins with the small ubiquitin-like modifier (SUMO) regulates protein function in the context of cell cycle and DNA repair. The occurrence of SUMOylation is less frequent as compared to protein modification with ubiquitin, and appears to be controlled by a sma...

  11. Mass Spectrometry-Based Metabolomics of Agave Sap (Agave salmiana after Its Inoculation with Microorganisms Isolated from Agave Sap Concentrate Selected to Enhance Anticancer Activity

    Directory of Open Access Journals (Sweden)

    Luis M. Figueroa

    2017-11-01

    Full Text Available Saponins have been correlated with the reduction of cancer cell growth and the apoptotic effect of agave sap concentrate. Empirical observations of this artisanal Mexican food have shown that fermentation occurs after agave sap is concentrated, but little is known about the microorganisms that survive after cooking, or their effects on saponins and other metabolites. The aim of this study was to evaluate the changes in metabolites found in agave (A. salmiana sap after its fermentation with microorganisms isolated from agave sap concentrate, and demonstrate its potential use to enhance anticancer activity. Microorganisms were isolated by dilution plating and identified by 16S rRNA analysis. Isolates were used to ferment agave sap, and their corresponding butanolic extracts were compared with those that enhanced the cytotoxic activity on colon (Caco-2 and liver (Hep-G2 cancer cells. Metabolite changes were investigated by mass spectrometry-based metabolomics. Among 69 isolated microorganisms, the actinomycetes Arthrobacter globiformis and Gordonia sp. were used to analyze the metabolites, along with bioactivity changes. From the 939 ions that were mainly responsible for variation among fermented samples at 48 h, 96 h, and 192 h, four were correlated to anticancer activity. It was shown that magueyoside B, a kammogenin glycoside, was found at higher intensities in the samples fermented with Gordonia sp. that reduced Hep-G2 viability better than controls. These findings showed that microorganisms from agave sap concentrate change agave sap metabolites such as saponins. Butanolic extracts obtained after agave sap fermentation with Arthrobacter globiformis or Gordonia sp. increased the cancer cell growth inhibitory effect on colon or liver cancer cells, respectively.

  12. A Machine Learning Application Based in Random Forest for Integrating Mass Spectrometry-Based Metabolomic Data: A Simple Screening Method for Patients With Zika Virus

    Directory of Open Access Journals (Sweden)

    Carlos Fernando Odir Rodrigues Melo

    2018-04-01

    Full Text Available Recent Zika outbreaks in South America, accompanied by unexpectedly severe clinical complications have brought much interest in fast and reliable screening methods for ZIKV (Zika virus identification. Reverse-transcriptase polymerase chain reaction (RT-PCR is currently the method of choice to detect ZIKV in biological samples. This approach, nonetheless, demands a considerable amount of time and resources such as kits and reagents that, in endemic areas, may result in a substantial financial burden over affected individuals and health services veering away from RT-PCR analysis. This study presents a powerful combination of high-resolution mass spectrometry and a machine-learning prediction model for data analysis to assess the existence of ZIKV infection across a series of patients that bear similar symptomatic conditions, but not necessarily are infected with the disease. By using mass spectrometric data that are inputted with the developed decision-making algorithm, we were able to provide a set of features that work as a “fingerprint” for this specific pathophysiological condition, even after the acute phase of infection. Since both mass spectrometry and machine learning approaches are well-established and have largely utilized tools within their respective fields, this combination of methods emerges as a distinct alternative for clinical applications, providing a diagnostic screening—faster and more accurate—with improved cost-effectiveness when compared to existing technologies.

  13. A Machine Learning Application Based in Random Forest for Integrating Mass Spectrometry-Based Metabolomic Data: A Simple Screening Method for Patients With Zika Virus.

    Science.gov (United States)

    Melo, Carlos Fernando Odir Rodrigues; Navarro, Luiz Claudio; de Oliveira, Diogo Noin; Guerreiro, Tatiane Melina; Lima, Estela de Oliveira; Delafiori, Jeany; Dabaja, Mohamed Ziad; Ribeiro, Marta da Silva; de Menezes, Maico; Rodrigues, Rafael Gustavo Martins; Morishita, Karen Noda; Esteves, Cibele Zanardi; de Amorim, Aline Lopes Lucas; Aoyagui, Caroline Tiemi; Parise, Pierina Lorencini; Milanez, Guilherme Paier; do Nascimento, Gabriela Mansano; Ribas Freitas, André Ricardo; Angerami, Rodrigo; Costa, Fábio Trindade Maranhão; Arns, Clarice Weis; Resende, Mariangela Ribeiro; Amaral, Eliana; Junior, Renato Passini; Ribeiro-do-Valle, Carolina C; Milanez, Helaine; Moretti, Maria Luiza; Proenca-Modena, Jose Luiz; Avila, Sandra; Rocha, Anderson; Catharino, Rodrigo Ramos

    2018-01-01

    Recent Zika outbreaks in South America, accompanied by unexpectedly severe clinical complications have brought much interest in fast and reliable screening methods for ZIKV (Zika virus) identification. Reverse-transcriptase polymerase chain reaction (RT-PCR) is currently the method of choice to detect ZIKV in biological samples. This approach, nonetheless, demands a considerable amount of time and resources such as kits and reagents that, in endemic areas, may result in a substantial financial burden over affected individuals and health services veering away from RT-PCR analysis. This study presents a powerful combination of high-resolution mass spectrometry and a machine-learning prediction model for data analysis to assess the existence of ZIKV infection across a series of patients that bear similar symptomatic conditions, but not necessarily are infected with the disease. By using mass spectrometric data that are inputted with the developed decision-making algorithm, we were able to provide a set of features that work as a "fingerprint" for this specific pathophysiological condition, even after the acute phase of infection. Since both mass spectrometry and machine learning approaches are well-established and have largely utilized tools within their respective fields, this combination of methods emerges as a distinct alternative for clinical applications, providing a diagnostic screening-faster and more accurate-with improved cost-effectiveness when compared to existing technologies.

  14. Ranked solutions to a class of combinatorial optimizations—with applications in mass spectrometry based peptide sequencing and a variant of directed paths in random media

    Science.gov (United States)

    Doerr, Timothy P.; Alves, Gelio; Yu, Yi-Kuo

    2005-08-01

    Typical combinatorial optimizations are NP-hard; however, for a particular class of cost functions the corresponding combinatorial optimizations can be solved in polynomial time using the transfer matrix technique or, equivalently, the dynamic programming approach. This suggests a way to efficiently find approximate solutions-find a transformation that makes the cost function as similar as possible to that of the solvable class. After keeping many high-ranking solutions using the approximate cost function, one may then re-assess these solutions with the full cost function to find the best approximate solution. Under this approach, it is important to be able to assess the quality of the solutions obtained, e.g., by finding the true ranking of the kth best approximate solution when all possible solutions are considered exhaustively. To tackle this statistical issue, we provide a systematic method starting with a scaling function generated from the finite number of high-ranking solutions followed by a convergent iterative mapping. This method, useful in a variant of the directed paths in random media problem proposed here, can also provide a statistical significance assessment for one of the most important proteomic tasks-peptide sequencing using tandem mass spectrometry data. For directed paths in random media, the scaling function depends on the particular realization of randomness; in the mass spectrometry case, the scaling function is spectrum-specific.

  15. Qupe--a Rich Internet Application to take a step forward in the analysis of mass spectrometry-based quantitative proteomics experiments.

    Science.gov (United States)

    Albaum, Stefan P; Neuweger, Heiko; Fränzel, Benjamin; Lange, Sita; Mertens, Dominik; Trötschel, Christian; Wolters, Dirk; Kalinowski, Jörn; Nattkemper, Tim W; Goesmann, Alexander

    2009-12-01

    The goal of present -omics sciences is to understand biological systems as a whole in terms of interactions of the individual cellular components. One of the main building blocks in this field of study is proteomics where tandem mass spectrometry (LC-MS/MS) in combination with isotopic labelling techniques provides a common way to obtain a direct insight into regulation at the protein level. Methods to identify and quantify the peptides contained in a sample are well established, and their output usually results in lists of identified proteins and calculated relative abundance values. The next step is to move ahead from these abstract lists and apply statistical inference methods to compare measurements, to identify genes that are significantly up- or down-regulated, or to detect clusters of proteins with similar expression profiles. We introduce the Rich Internet Application (RIA) Qupe providing comprehensive data management and analysis functions for LC-MS/MS experiments. Starting with the import of mass spectra data the system guides the experimenter through the process of protein identification by database search, the calculation of protein abundance ratios, and in particular, the statistical evaluation of the quantification results including multivariate analysis methods such as analysis of variance or hierarchical cluster analysis. While a data model to store these results has been developed, a well-defined programming interface facilitates the integration of novel approaches. A compute cluster is utilized to distribute computationally intensive calculations, and a web service allows to interchange information with other -omics software applications. To demonstrate that Qupe represents a step forward in quantitative proteomics analysis an application study on Corynebacterium glutamicum has been carried out. Qupe is implemented in Java utilizing Hibernate, Echo2, R and the Spring framework. We encourage the usage of the RIA in the sense of the 'software as a

  16. Interrogating the Plasmodium Sporozoite Surface: Identification of Surface-Exposed Proteins and Demonstration of Glycosylation on CSP and TRAP by Mass Spectrometry-Based Proteomics.

    Directory of Open Access Journals (Sweden)

    Kristian E Swearingen

    2016-04-01

    Full Text Available Malaria parasite infection is initiated by the mosquito-transmitted sporozoite stage, a highly motile invasive cell that targets hepatocytes in the liver for infection. A promising approach to developing a malaria vaccine is the use of proteins located on the sporozoite surface as antigens to elicit humoral immune responses that prevent the establishment of infection. Very little of the P. falciparum genome has been considered as potential vaccine targets, and candidate vaccines have been almost exclusively based on single antigens, generating the need for novel target identification. The most advanced malaria vaccine to date, RTS,S, a subunit vaccine consisting of a portion of the major surface protein circumsporozoite protein (CSP, conferred limited protection in Phase III trials, falling short of community-established vaccine efficacy goals. In striking contrast to the limited protection seen in current vaccine trials, sterilizing immunity can be achieved by immunization with radiation-attenuated sporozoites, suggesting that more potent protection may be achievable with a multivalent protein vaccine. Here, we provide the most comprehensive analysis to date of proteins located on the surface of or secreted by Plasmodium falciparum salivary gland sporozoites. We used chemical labeling to isolate surface-exposed proteins on sporozoites and identified these proteins by mass spectrometry. We validated several of these targets and also provide evidence that components of the inner membrane complex are in fact surface-exposed and accessible to antibodies in live sporozoites. Finally, our mass spectrometry data provide the first direct evidence that the Plasmodium surface proteins CSP and TRAP are glycosylated in sporozoites, a finding that could impact the selection of vaccine antigens.

  17. Determination of total concentration of chemically labeled metabolites as a means of metabolome sample normalization and sample loading optimization in mass spectrometry-based metabolomics.

    Science.gov (United States)

    Wu, Yiman; Li, Liang

    2012-12-18

    For mass spectrometry (MS)-based metabolomics, it is important to use the same amount of starting materials from each sample to compare the metabolome changes in two or more comparative samples. Unfortunately, for biological samples, the total amount or concentration of metabolites is difficult to determine. In this work, we report a general approach of determining the total concentration of metabolites based on the use of chemical labeling to attach a UV absorbent to the metabolites to be analyzed, followed by rapid step-gradient liquid chromatography (LC) UV detection of the labeled metabolites. It is shown that quantification of the total labeled analytes in a biological sample facilitates the preparation of an appropriate amount of starting materials for MS analysis as well as the optimization of the sample loading amount to a mass spectrometer for achieving optimal detectability. As an example, dansylation chemistry was used to label the amine- and phenol-containing metabolites in human urine samples. LC-UV quantification of the labeled metabolites could be optimally performed at the detection wavelength of 338 nm. A calibration curve established from the analysis of a mixture of 17 labeled amino acid standards was found to have the same slope as that from the analysis of the labeled urinary metabolites, suggesting that the labeled amino acid standard calibration curve could be used to determine the total concentration of the labeled urinary metabolites. A workflow incorporating this LC-UV metabolite quantification strategy was then developed in which all individual urine samples were first labeled with (12)C-dansylation and the concentration of each sample was determined by LC-UV. The volumes of urine samples taken for producing the pooled urine standard were adjusted to ensure an equal amount of labeled urine metabolites from each sample was used for the pooling. The pooled urine standard was then labeled with (13)C-dansylation. Equal amounts of the (12)C

  18. Metrological traceability in mass spectrometry-based targeted protein quantitation: a proof-of-principle study for serum apolipoproteins A-I and B100.

    Science.gov (United States)

    Smit, Nico P M; Romijn, Fred P H T M; van den Broek, Irene; Drijfhout, Jan W; Haex, Martin; van der Laarse, Arnoud; van der Burgt, Yuri E M; Cobbaert, Christa M

    2014-09-23

    In this study, we have followed up on previous liquid chromatography (LC) multiple reaction monitoring (MRM) mass spectrometry (MS) approaches for measurement of apolipoprotein (apo) A-I and apo B100 in serum aiming for implementation of a multiplexed assay in a clinical chemistry laboratory with full metrological traceability. Signature peptides were selected and detected by dynamic MRM, and stable isotope labeled (SIL)-peptides were used as internal standards. Five apo A-I and four apo B100 peptides were measured in serum digests with linearity (R(2)>0.992) in the physiologically relevant concentration ranges. Linearity with regard to protein concentration was ascertained at five concentration levels (R(2)>0.926 and R(2)>0.965, for the apo A-I and apo B100 peptides, respectively). Three native value-assigned sera were used as external calibrators for further method verification. Imprecision values on sample preparation and LC-MS/MS acquisition were below the established minimal specifications for apo A-I and apo B100 (5.0% and 5.3%, respectively). Correlation of LC-MS/MS results with immunoturbidimetric assay results, for normo- and hypertriglyceridemic samples, showed R(2)>0.944 for apo A-I and R(2)>0.964 for apo B100. This LC-MS/MS method has potential for clinical application in normo- and dyslipidemic patients. Measurement of apo A-I and apo B100 may offer an alternative to high and low density lipoprotein cholesterol (HDL-c and LDL-c) methods for cardiovascular disease risk assessment in dyslipidemic patients [1]. An LC-MS/MS method for apo A-I and apo B100 has the advantage of antibody independent and specific detection of protein signature peptides. The introduction of an LC-MS/MS method for apo A-I and apo B100 can serve as an example for many existing and newly developed (multiplex) biomarker methods in quantitative clinical chemistry proteomics (qCCP). Such LC-MS/MS methods should meet basic clinical chemistry principles with regard to test evaluation

  19. Analysis of drugs of forensic interest with capillary zone electrophoresis/time-of-flight mass spectrometry based on the use of non-volatile buffers.

    Science.gov (United States)

    Gottardo, Rossella; Mikšík, Ivan; Aturki, Zeineb; Sorio, Daniela; Seri, Catia; Fanali, Salvatore; Tagliaro, Franco

    2012-02-01

    The present work is aimed at investigating the influence of the background electrolyte composition and concentration on the separation efficiency and resolution and mass spectrometric detection of illicit drugs in a capillary zone electrophoresis-electrospray ionization-time of flight mass spectrometry (CZE-ESI-TOF MS) system. The effect of phosphate, borate and Tris buffers on the separation and mass spectrometry response of a mixture of 3,4-methylenedioxyamphetamine, 3,4-methylenedioxymethamphetamine, methadone, cocaine, morphine, codeine and 6-monoacetylmorphine was studied, in comparison with a reference ammonium formate separation buffer. Inorganic non-volatile borate and Tris buffers proved hardly suitable for capillary electrophoresis-mass spectrometry (CE-MS) analysis, but quite unexpectedly ammonium phosphate buffers showed good separation and ionization performances for all the analytes tested. Applications of this method to real samples of hair from drug addicts are also provided. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  20. Ion trace detection algorithm to extract pure ion chromatograms to improve untargeted peak detection quality for liquid chromatography/time-of-flight mass spectrometry-based metabolomics data.

    Science.gov (United States)

    Wang, San-Yuan; Kuo, Ching-Hua; Tseng, Yufeng J

    2015-03-03

    Able to detect known and unknown metabolites, untargeted metabolomics has shown great potential in identifying novel biomarkers. However, elucidating all possible liquid chromatography/time-of-flight mass spectrometry (LC/TOF-MS) ion signals in a complex biological sample remains challenging since many ions are not the products of metabolites. Methods of reducing ions not related to metabolites or simply directly detecting metabolite related (pure) ions are important. In this work, we describe PITracer, a novel algorithm that accurately detects the pure ions of a LC/TOF-MS profile to extract pure ion chromatograms and detect chromatographic peaks. PITracer estimates the relative mass difference tolerance of ions and calibrates the mass over charge (m/z) values for peak detection algorithms with an additional option to further mass correction with respect to a user-specified metabolite. PITracer was evaluated using two data sets containing 373 human metabolite standards, including 5 saturated standards considered to be split peaks resultant from huge m/z fluctuation, and 12 urine samples spiked with 50 forensic drugs of varying concentrations. Analysis of these data sets show that PITracer correctly outperformed existing state-of-art algorithm and extracted the pure ion chromatograms of the 5 saturated standards without generating split peaks and detected the forensic drugs with high recall, precision, and F-score and small mass error.

  1. Custom database development and biomarker discovery methods for MALDI-TOF mass spectrometry-based identification of high-consequence bacterial pathogens.

    Science.gov (United States)

    Tracz, Dobryan M; Tyler, Andrea D; Cunningham, Ian; Antonation, Kym S; Corbett, Cindi R

    2017-03-01

    A high-quality custom database of MALDI-TOF mass spectral profiles was developed with the goal of improving clinical diagnostic identification of high-consequence bacterial pathogens. A biomarker discovery method is presented for identifying and evaluating MALDI-TOF MS spectra to potentially differentiate biothreat bacteria from less-pathogenic near-neighbour species. Crown Copyright © 2017. Published by Elsevier B.V. All rights reserved.

  2. PhosProtect - a novel and superior compound to tag and protect phospho-groups during mass spectrometry based phospho-proteomics

    DEFF Research Database (Denmark)

    2012-01-01

    Value Proposition The PhosProtect compound alone (developed and tested, IP secured)* • protects phospho-groups during tandem mass spectrometry, thus reducing problematic neutral loss of phosphate. • provides unique phospho-tag by causing isotopic distribution patterns in MS and MS/MS data. The PhosProtect...... compound covalently bound to column material (in progress , IP secured)** • Combines enrichment, protection and tagging of phospho-peptides and phospho-lipids in one easy workflow....

  3. Fenofibrate Metabolism in the Cynomolgus Monkey using Ultraperformance Liquid Chromatography-Quadrupole Time-of-Flight Mass Spectrometry-Based MetabolomicsS⃞

    Science.gov (United States)

    Liu, Aiming; Patterson, Andrew D.; Yang, Zongtao; Zhang, Xinying; Liu, Wei; Qiu, Fayang; Sun, He; Krausz, Kristopher W.; Idle, Jeffrey R.; Gonzalez, Frank J.; Dai, Renke

    2009-01-01

    Fenofibrate, widely used for the treatment of dyslipidemia, activates the nuclear receptor, peroxisome proliferator-activated receptor α. However, liver toxicity, including liver cancer, occurs in rodents treated with fibrate drugs. Marked species differences occur in response to fibrate drugs, especially between rodents and humans, the latter of which are resistant to fibrate-induced cancer. Fenofibrate metabolism, which also shows species differences, has not been fully determined in humans and surrogate primates. In the present study, the metabolism of fenofibrate was investigated in cynomolgus monkeys by ultraperformance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-QTOFMS)-based metabolomics. Urine samples were collected before and after oral doses of fenofibrate. The samples were analyzed in both positive-ion and negative-ion modes by UPLC-QTOFMS, and after data deconvolution, the resulting data matrices were subjected to multivariate data analysis. Pattern recognition was performed on the retention time, mass/charge ratio, and other metabolite-related variables. Synthesized or purchased authentic compounds were used for metabolite identification and structure elucidation by liquid chromatographytandem mass spectrometry. Several metabolites were identified, including fenofibric acid, reduced fenofibric acid, fenofibric acid ester glucuronide, reduced fenofibric acid ester glucuronide, and compound X. Another two metabolites (compound B and compound AR), not previously reported in other species, were characterized in cynomolgus monkeys. More importantly, previously unknown metabolites, fenofibric acid taurine conjugate and reduced fenofibric acid taurine conjugate were identified, revealing a previously unrecognized conjugation pathway for fenofibrate. PMID:19251819

  4. Galaxy-M: a Galaxy workflow for processing and analyzing direct infusion and liquid chromatography mass spectrometry-based metabolomics data.

    Science.gov (United States)

    Davidson, Robert L; Weber, Ralf J M; Liu, Haoyu; Sharma-Oates, Archana; Viant, Mark R

    2016-01-01

    Metabolomics is increasingly recognized as an invaluable tool in the biological, medical and environmental sciences yet lags behind the methodological maturity of other omics fields. To achieve its full potential, including the integration of multiple omics modalities, the accessibility, standardization and reproducibility of computational metabolomics tools must be improved significantly. Here we present our end-to-end mass spectrometry metabolomics workflow in the widely used platform, Galaxy. Named Galaxy-M, our workflow has been developed for both direct infusion mass spectrometry (DIMS) and liquid chromatography mass spectrometry (LC-MS) metabolomics. The range of tools presented spans from processing of raw data, e.g. peak picking and alignment, through data cleansing, e.g. missing value imputation, to preparation for statistical analysis, e.g. normalization and scaling, and principal components analysis (PCA) with associated statistical evaluation. We demonstrate the ease of using these Galaxy workflows via the analysis of DIMS and LC-MS datasets, and provide PCA scores and associated statistics to help other users to ensure that they can accurately repeat the processing and analysis of these two datasets. Galaxy and data are all provided pre-installed in a virtual machine (VM) that can be downloaded from the GigaDB repository. Additionally, source code, executables and installation instructions are available from GitHub. The Galaxy platform has enabled us to produce an easily accessible and reproducible computational metabolomics workflow. More tools could be added by the community to expand its functionality. We recommend that Galaxy-M workflow files are included within the supplementary information of publications, enabling metabolomics studies to achieve greater reproducibility.

  5. Development of SI-traceable C-peptide certified reference material NMIJ CRM 6901-a using isotope-dilution mass spectrometry-based amino acid analyses.

    Science.gov (United States)

    Kinumi, Tomoya; Goto, Mari; Eyama, Sakae; Kato, Megumi; Kasama, Takeshi; Takatsu, Akiko

    2012-07-01

    A certified reference material (CRM) is a higher-order calibration material used to enable a traceable analysis. This paper describes the development of a C-peptide CRM (NMIJ CRM 6901-a) by the National Metrology Institute of Japan using two independent methods for amino acid analysis based on isotope-dilution mass spectrometry. C-peptide is a 31-mer peptide that is utilized for the evaluation of β-cell function in the pancreas in clinical testing. This CRM is a lyophilized synthetic peptide having the human C-peptide sequence, and contains deamidated and pyroglutamylated forms of C-peptide. By adding water (1.00 ± 0.01) g into the vial containing the CRM, the C-peptide solution in 10 mM phosphate buffer saline (pH 6.6) is reconstituted. We assigned two certified values that represent the concentrations of total C-peptide (mixture of C-peptide, deamidated C-peptide, and pyroglutamylated C-peptide) and C-peptide. The certified concentration of total C-peptide was determined by two amino acid analyses using pre-column derivatization liquid chromatography-mass spectrometry and hydrophilic chromatography-mass spectrometry following acid hydrolysis. The certified concentration of C-peptide was determined by multiplying the concentration of total C-peptide by the ratio of the relative area of C-peptide to that of the total C-peptide measured by liquid chromatography. The certified value of C-peptide (80.7 ± 5.0) mg/L represents the concentration of the specific entity of C-peptide; on the other hand, the certified value of total C-peptide, (81.7 ± 5.1) mg/L can be used for analyses that does not differentiate deamidated and pyroglutamylated C-peptide from C-peptide itself, such as amino acid analyses and immunochemical assays.

  6. MetCCS predictor: a web server for predicting collision cross-section values of metabolites in ion mobility-mass spectrometry based metabolomics.

    Science.gov (United States)

    Zhou, Zhiwei; Xiong, Xin; Zhu, Zheng-Jiang

    2017-07-15

    In metabolomics, rigorous structural identification of metabolites presents a challenge for bioinformatics. The use of collision cross-section (CCS) values of metabolites derived from ion mobility-mass spectrometry effectively increases the confidence of metabolite identification, but this technique suffers from the limit number of available CCS values. Currently, there is no software available for rapidly generating the metabolites' CCS values. Here, we developed the first web server, namely, MetCCS Predictor, for predicting CCS values. It can predict the CCS values of metabolites using molecular descriptors within a few seconds. Common users with limited background on bioinformatics can benefit from this software and effectively improve the metabolite identification in metabolomics. The web server is freely available at: http://www.metabolomics-shanghai.org/MetCCS/ . jiangzhu@sioc.ac.cn. Supplementary data are available at Bioinformatics online. © The Author (2017). Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com

  7. High performance mass spectrometry based proteomics reveals enzyme and signaling pathway regulation in neutrophils during the early stage of surgical trauma

    DEFF Research Database (Denmark)

    Arshid, Samina; Tahir, Muhammad; Fontes, Belchor

    2017-01-01

    and surgical trauma rats in this study. Extracted proteins were analyzed using nano liquid chromatography coupled to tandem mass spectrometry. A total of 2924 rat neutrophil proteins were identified in our analysis, of which 393 were found differentially regulated between control and trauma groups. By using...... functional pathways analysis of the 190 proteins up-regulated in surgical trauma we found proteins related to transcription initiation and protein biosynthesis. On the other hand, among the 203 proteins down-regulated in surgical trauma we found enrichment for proteins of the immune response, proteasome...... degradation and actin cytoskeleton. Overall, enzyme prediction analysis revealed that regulated enzymes are directly involved in neutrophil apoptosis, directional migration and chemotaxis. Our observations were then confirmed by in silico protein-protein interaction analysis. Collectively, our results reveal...

  8. Liquid Chromatography–Mass Spectrometry Based Metabolomics Study of Cloned versus Normal Pigs Fed Either Restricted or Ad Libitum High-Energy Diets

    DEFF Research Database (Denmark)

    Christensen, Kirstine Lykke; Hedemann, Mette Skou; Jørgensen, Henry

    2012-01-01

    Genetically identical cloned pigs should in principle eliminate biological variation and provide more pronounced effects when subjected to, e.g., dietary interventions, but little is known about how phenotype and phenotypic variation is affected by cloning. Therefore, an investigation...... of the metabolome of cloned pigs compared to normal control pigs was performed to elucidate the variation and possible differences in the metabolic phenotypes during a dietary intervention. A total of 19 control pigs and 17 cloned pigs were given the same high-energy dense diet either ad libitum or in a restricted...... manner (60% of ad libitum) for 6 months, and plasma was subjected to liquid chromatography–mass spectrometry nontargeted metabolomics and biochemical analyses. Low systemic levels of IGF-1 could indicate altered growth conditions and energy metabolism in cloned pigs. In response to ad libitum feeding...

  9. Synthesis of stable isotopically labeled peptides with filter-assisted enzymatic labeling for the diagnosis of hepatitis B virus infection utilizing mass spectrometry-based proteomics strategy

    International Nuclear Information System (INIS)

    Tsai, Hsing-Fen; Hsiao, He-Hsuan

    2017-01-01

    A facile method for the preparation of stable isotopically labeled peptides was developed by means of filter-assisted tryptic "1"6O/"1"8O water labeling, which could be directly applied to the determination of hepatitis B virus infection from human serum with tandem mass spectrometry. Tryptic peptides of hepatitis B surface antigen or hepatitis B e antigen from different subtypes of hepatitis B virus were synthesized with traditional solid-phase peptide synthesis as potential biomarkers. Trypsin catalyzed oxygen-18 exchange at their amidated c-terminus of arginine or lysine residue. The protease catalyzed oxygen-18 to oxygen-16 back exchange reaction was eliminated due to the complete removal of trypsin by the centrifugal filter containing a thin membrane associated with molecular weight cut-off of 10 KDa. The synthetic isotopic peptides were spiked into trichloroacetic acid/acetone precipitated human serum as internal standards and were selectively detected with multiplexed parallel reaction monitoring on a hybrid quadrupole-orbitrap mass spectrometer. The limit of detection for all synthetic peptides were in the range of 0.09 fmol–1.13 fmol. The results indicated that the peptide YLWEWASVR derived from hepatitis B surface antigen was quantified approximately 200 fmol per μl serum and may serve as a diagnostic biomarker for the detection of hepatitis B virus infected disease. - Highlights: • Facile synthesis of an inexpensive and highly reproducible stable isotopically labeled peptides. • Complete incorporation of two "1"8O atoms into synthesized peptides with filter-assisted enzymatic labeling. • Targeted analysis with parallel reaction monitoring assay for the disease diagnosis.

  10. Synthesis of stable isotopically labeled peptides with filter-assisted enzymatic labeling for the diagnosis of hepatitis B virus infection utilizing mass spectrometry-based proteomics strategy

    Energy Technology Data Exchange (ETDEWEB)

    Tsai, Hsing-Fen; Hsiao, He-Hsuan, E-mail: hhhsiao@dragon.nchu.edu.tw

    2017-03-01

    A facile method for the preparation of stable isotopically labeled peptides was developed by means of filter-assisted tryptic {sup 16}O/{sup 18}O water labeling, which could be directly applied to the determination of hepatitis B virus infection from human serum with tandem mass spectrometry. Tryptic peptides of hepatitis B surface antigen or hepatitis B e antigen from different subtypes of hepatitis B virus were synthesized with traditional solid-phase peptide synthesis as potential biomarkers. Trypsin catalyzed oxygen-18 exchange at their amidated c-terminus of arginine or lysine residue. The protease catalyzed oxygen-18 to oxygen-16 back exchange reaction was eliminated due to the complete removal of trypsin by the centrifugal filter containing a thin membrane associated with molecular weight cut-off of 10 KDa. The synthetic isotopic peptides were spiked into trichloroacetic acid/acetone precipitated human serum as internal standards and were selectively detected with multiplexed parallel reaction monitoring on a hybrid quadrupole-orbitrap mass spectrometer. The limit of detection for all synthetic peptides were in the range of 0.09 fmol–1.13 fmol. The results indicated that the peptide YLWEWASVR derived from hepatitis B surface antigen was quantified approximately 200 fmol per μl serum and may serve as a diagnostic biomarker for the detection of hepatitis B virus infected disease. - Highlights: • Facile synthesis of an inexpensive and highly reproducible stable isotopically labeled peptides. • Complete incorporation of two {sup 18}O atoms into synthesized peptides with filter-assisted enzymatic labeling. • Targeted analysis with parallel reaction monitoring assay for the disease diagnosis.

  11. Web Server for Peak Detection, Baseline Correction, and Alignment in Two-Dimensional Gas Chromatography Mass Spectrometry-Based Metabolomics Data.

    Science.gov (United States)

    Tian, Tze-Feng; Wang, San-Yuan; Kuo, Tien-Chueh; Tan, Cheng-En; Chen, Guan-Yuan; Kuo, Ching-Hua; Chen, Chi-Hsin Sally; Chan, Chang-Chuan; Lin, Olivia A; Tseng, Y Jane

    2016-11-01

    Two-dimensional gas chromatography time-of-flight mass spectrometry (GC×GC/TOF-MS) is superior for chromatographic separation and provides great sensitivity for complex biological fluid analysis in metabolomics. However, GC×GC/TOF-MS data processing is currently limited to vendor software and typically requires several preprocessing steps. In this work, we implement a web-based platform, which we call GC 2 MS, to facilitate the application of recent advances in GC×GC/TOF-MS, especially for metabolomics studies. The core processing workflow of GC 2 MS consists of blob/peak detection, baseline correction, and blob alignment. GC 2 MS treats GC×GC/TOF-MS data as pictures and clusters the pixels as blobs according to the brightness of each pixel to generate a blob table. GC 2 MS then aligns the blobs of two GC×GC/TOF-MS data sets according to their distance and similarity. The blob distance and similarity are the Euclidean distance of the first and second retention times of two blobs and the Pearson's correlation coefficient of the two mass spectra, respectively. GC 2 MS also directly corrects the raw data baseline. The analytical performance of GC 2 MS was evaluated using GC×GC/TOF-MS data sets of Angelica sinensis compounds acquired under different experimental conditions and of human plasma samples. The results show that GC 2 MS is an easy-to-use tool for detecting peaks and correcting baselines, and GC 2 MS is able to align GC×GC/TOF-MS data sets acquired under different experimental conditions. GC 2 MS is freely accessible at http://gc2ms.web.cmdm.tw .

  12. Data on mass spectrometry-based proteomics for studying the involvement of CYLD in the ubiquitination events downstream of EGFR activation

    Directory of Open Access Journals (Sweden)

    Virginia Sanchez-Quiles

    2018-06-01

    Full Text Available The present data article corresponds to the proteomic data of the involvement of Cylindromatosis protein (CYLD in the ubiquitination signaling initiated by EGF stimulation. CYLD tumor suppressor protein has Lys63-chain deubiquitinase activity that has been proved essential for the negative regulation of crucial signaling mechanisms, namely the NFkB pathway. Previous results have suggested the involvement of CYLD in the EGF-dependent signal transduction as well, showing its engagement within the tyrosine-phosphorylated complexes formed following the addition of the growth factor. EGFR signaling participates in central cellular processes and its tight regulation, partly through ubiquitination cascades, is decisive for a balanced cellular homeostasis. We carried out the substitution of the endogenous pool of ubiquitin for a His-FLAG-tagged ubiquitin (Stable Ubiquitin Exchange, StUbEx, in combination with the shRNA silencing of CYLD and SILAC-labeling on HeLa cells. The subsequent tandem affinity purification of ubiquitinated proteins in control and CYLD-depleted cells was followed by mass spectrometric analysis. Therefore, we present an unbiased study investigating the impact of CYLD in the EGF-dependent ubiquitination. The data supplied herein is related to the research article entitled “Cylindromatosis tumor suppressor protein (CYLD deubiquitinase is necessary for proper ubiquitination and degradation of the epidermal growth factor receptor” (Sanchez-Quiles et al., 2017 [1]. We provide the associated mass spectrometry raw files, excel tables and gene ontology enrichments. The data have been deposited in the ProteomeXchange with the identifier PXD003423.

  13. [Determination of 51 carbamate pesticide residues in vegetables by liquid chromatography-tandem mass spectrometry based on optimization of QuEChERS sample preparation method].

    Science.gov (United States)

    Wang, Lianzhu; Zhou, Yu; Huang, Xiaoyan; Wang, Ruilong; Lin, Zixu; Chen, Yong; Wang, Dengfei; Lin, Dejuan; Xu, Dunming

    2013-12-01

    The raw extracts of six vegetables (tomato, green bean, shallot, broccoli, ginger and carrot) were analyzed using gas chromatography-mass spectrometry (GC-MS) in full scan mode combined with NIST library search to confirm main matrix compounds. The effects of cleanup and adsorption mechanisms of primary secondary amine (PSA) , octadecylsilane (C18) and PSA + C18 on co-extractives were studied by the weight of evaporation residue for extracts before and after cleanup. The suitability of the two versions of QuEChERS method for sample preparation was evaluated for the extraction of 51 carbamate pesticides in the six vegetables. One of the QuEChERS methods was the original un-buffered method published in 2003, and the other was AOAC Official Method 2007.01 using acetate buffer. As a result, the best effects were obtained from using the combination of C18 and PSA for extract cleanup in vegetables. The acetate-buffered version was suitable for the determination of all pesticides except dioxacarb. Un-buffered QuEChERS method gave satisfactory results for determining dioxacarb. Based on these results, the suitable QuEChERS sample preparation method and liquid chromatography-positive electrospray ionization-tandem mass spectrometry under the optimized conditions were applied to determine the 51 carbamate pesticide residues in six vegetables. The analytes were quantified by matrix-matched standard solution. The recoveries at three levels of 10, 20 and 100 microg/kg spiked in six vegetables ranged from 58.4% to 126% with the relative standard deviations of 3.3%-26%. The limits of quantification (LOQ, S/N > or = 10) were 0.2-10 microg/kg except that the LOQs of cartap and thiofanox were 50 microg/kg. The method is highly efficient, sensitive and suitable for monitoring the 51 carbamate pesticide residues in vegetables.

  14. Ultra-performance liquid chromatography-tandem mass spectrometry-based multiplex enzyme assay for six enzymes associated with hereditary hemolytic anemia.

    Science.gov (United States)

    Park, Chul Min; Lee, Kyunghoon; Jun, Sun-Hee; Song, Sang Hoon; Song, Junghan

    2017-08-15

    Deficiencies in erythrocyte metabolic enzymes are associated with hereditary hemolytic anemia. Here, we report the development of a novel multiplex enzyme assay for six major enzymes, namely glucose-6-phosphate dehydrogenase, pyruvate kinase, pyrimidine 5'-nucleotidase, hexokinase, triosephosphate isomerase, and adenosine deaminase, deficiencies in which are implicated in erythrocyte enzymopathies. To overcome the drawbacks of traditional spectrophotometric enzyme assays, the present assay was based on ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). The products of the six enzymes were directly measured by using ion pairing UPLC-MS/MS, and the precision, linearity, ion suppression, optimal sample amounts, and incubation times were evaluated. Eighty-three normal individuals and 13 patients with suspected enzymopathy were analyzed. The UPLC running time was within 5min. No ion suppression was observed at the retention time for the products or internal standards. We selected an optimal dilution factor and incubation time for each enzyme system. The intra- and inter-assay imprecision values (CVs) were 2.5-12.1% and 2.9-14.3%, respectively. The linearity of each system was good, with R 2 values >0.97. Patient samples showed consistently lower enzyme activities than those from normal individuals. The present ion paring UPLC-MS/MS assay enables facile and reproducible multiplex evaluation of the activity of enzymes implicated in enzymopathy-associated hemolytic anemia. Copyright © 2017 Elsevier B.V. All rights reserved.

  15. The mzTab data exchange format: communicating mass-spectrometry-based proteomics and metabolomics experimental results to a wider audience.

    Science.gov (United States)

    Griss, Johannes; Jones, Andrew R; Sachsenberg, Timo; Walzer, Mathias; Gatto, Laurent; Hartler, Jürgen; Thallinger, Gerhard G; Salek, Reza M; Steinbeck, Christoph; Neuhauser, Nadin; Cox, Jürgen; Neumann, Steffen; Fan, Jun; Reisinger, Florian; Xu, Qing-Wei; Del Toro, Noemi; Pérez-Riverol, Yasset; Ghali, Fawaz; Bandeira, Nuno; Xenarios, Ioannis; Kohlbacher, Oliver; Vizcaíno, Juan Antonio; Hermjakob, Henning

    2014-10-01

    The HUPO Proteomics Standards Initiative has developed several standardized data formats to facilitate data sharing in mass spectrometry (MS)-based proteomics. These allow researchers to report their complete results in a unified way. However, at present, there is no format to describe the final qualitative and quantitative results for proteomics and metabolomics experiments in a simple tabular format. Many downstream analysis use cases are only concerned with the final results of an experiment and require an easily accessible format, compatible with tools such as Microsoft Excel or R. We developed the mzTab file format for MS-based proteomics and metabolomics results to meet this need. mzTab is intended as a lightweight supplement to the existing standard XML-based file formats (mzML, mzIdentML, mzQuantML), providing a comprehensive summary, similar in concept to the supplemental material of a scientific publication. mzTab files can contain protein, peptide, and small molecule identifications together with experimental metadata and basic quantitative information. The format is not intended to store the complete experimental evidence but provides mechanisms to report results at different levels of detail. These range from a simple summary of the final results to a representation of the results including the experimental design. This format is ideally suited to make MS-based proteomics and metabolomics results available to a wider biological community outside the field of MS. Several software tools for proteomics and metabolomics have already adapted the format as an output format. The comprehensive mzTab specification document and extensive additional documentation can be found online. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

  16. The mzTab Data Exchange Format: Communicating Mass-spectrometry-based Proteomics and Metabolomics Experimental Results to a Wider Audience*

    Science.gov (United States)

    Griss, Johannes; Jones, Andrew R.; Sachsenberg, Timo; Walzer, Mathias; Gatto, Laurent; Hartler, Jürgen; Thallinger, Gerhard G.; Salek, Reza M.; Steinbeck, Christoph; Neuhauser, Nadin; Cox, Jürgen; Neumann, Steffen; Fan, Jun; Reisinger, Florian; Xu, Qing-Wei; del Toro, Noemi; Pérez-Riverol, Yasset; Ghali, Fawaz; Bandeira, Nuno; Xenarios, Ioannis; Kohlbacher, Oliver; Vizcaíno, Juan Antonio; Hermjakob, Henning

    2014-01-01

    The HUPO Proteomics Standards Initiative has developed several standardized data formats to facilitate data sharing in mass spectrometry (MS)-based proteomics. These allow researchers to report their complete results in a unified way. However, at present, there is no format to describe the final qualitative and quantitative results for proteomics and metabolomics experiments in a simple tabular format. Many downstream analysis use cases are only concerned with the final results of an experiment and require an easily accessible format, compatible with tools such as Microsoft Excel or R. We developed the mzTab file format for MS-based proteomics and metabolomics results to meet this need. mzTab is intended as a lightweight supplement to the existing standard XML-based file formats (mzML, mzIdentML, mzQuantML), providing a comprehensive summary, similar in concept to the supplemental material of a scientific publication. mzTab files can contain protein, peptide, and small molecule identifications together with experimental metadata and basic quantitative information. The format is not intended to store the complete experimental evidence but provides mechanisms to report results at different levels of detail. These range from a simple summary of the final results to a representation of the results including the experimental design. This format is ideally suited to make MS-based proteomics and metabolomics results available to a wider biological community outside the field of MS. Several software tools for proteomics and metabolomics have already adapted the format as an output format. The comprehensive mzTab specification document and extensive additional documentation can be found online. PMID:24980485

  17. Automation of dimethylation after guanidination labeling chemistry and its compatibility with common buffers and surfactants for mass spectrometry-based shotgun quantitative proteome analysis

    Energy Technology Data Exchange (ETDEWEB)

    Lo, Andy; Tang, Yanan; Chen, Lu; Li, Liang, E-mail: Liang.Li@ualberta.ca

    2013-07-25

    Graphical abstract: -- Highlights: •Dimethylation after guanidination (2MEGA) uses inexpensive reagents for isotopic labeling of peptides. •2MEGA can be optimized and automated for labeling peptides with high efficiency. •2MEGA is compatible with several commonly used cell lysis and protein solubilization reagents. •The automated 2MEGA labeling method can be used to handle a variety of protein samples for relative proteome quantification. -- Abstract: Isotope labeling liquid chromatography–mass spectrometry (LC–MS) is a major analytical platform for quantitative proteome analysis. Incorporation of isotopes used to distinguish samples plays a critical role in the success of this strategy. In this work, we optimized and automated a chemical derivatization protocol (dimethylation after guanidination, 2MEGA) to increase the labeling reproducibility and reduce human intervention. We also evaluated the reagent compatibility of this protocol to handle biological samples in different types of buffers and surfactants. A commercially available liquid handler was used for reagent dispensation to minimize analyst intervention and at least twenty protein digest samples could be prepared in a single run. Different front-end sample preparation methods for protein solubilization (SDS, urea, Rapigest™, and ProteaseMAX™) and two commercially available cell lysis buffers were evaluated for compatibility with the automated protocol. It was found that better than 94% desired labeling could be obtained in all conditions studied except urea, where the rate was reduced to about 92% due to carbamylation on the peptide amines. This work illustrates the automated 2MEGA labeling process can be used to handle a wide range of protein samples containing various reagents that are often encountered in protein sample preparation for quantitative proteome analysis.

  18. Determination of avian influenza A (H9N2) virions by inductively coupled plasma mass spectrometry based magnetic immunoassay with gold nanoparticles labeling

    Science.gov (United States)

    Xiao, Guangyang; Chen, Beibei; He, Man; Shi, Kaiwen; Zhang, Xing; Li, Xiaoting; Wu, Qiumei; Pang, Daiwen; Hu, Bin

    2017-12-01

    Avian influenza viruses are the pathogens of global poultry epidemics, and may even cause the human infections. Here, we proposed a novel inductively coupled plasma mass spectrometry (ICP-MS) based immunoassay with gold nanoparticles (Au NPs) labeling for the determination of H9N2 virions. Magnetic-beads modified with anti-influenza A H9N2 hemagglutinin mono-antibody (mAb-HA) were utilized for the capture of H9N2 virions in complex matrix; and Au NPs conjugated with mAb-HA were employed for the specific labeling of H9N2 virions for subsequent ICP-MS detection. With a sandwich immunoassay strategy, this method exhibited a high specificity for H9N2 among other influenza A virions such as H1N1 and H3N2. Under the optimized conditions, this method could detect as low as 0.63 ng mL- 1 H9N2 virions with the linear range of 2-400 ng mL- 1, the relative standard deviation for seven replicate detections of H9N2 virions was 7.2% (c = 10 ng mL- 1). The developed method was applied for the detection of H9N2 virions in real-world chicken dung samples, and the recovery for the spiking samples was 91.4-116.9%. This method is simple, rapid, sensitive, selective, reliable and has a good application potential for virions detection in real-world samples.

  19. Gas Chromatography/Mass Spectrometry-Based Metabolomic Profiling Reveals Alterations in Mouse Plasma and Liver in Response to Fava Beans.

    Science.gov (United States)

    Xiao, Man; Du, Guankui; Zhong, Guobing; Yan, Dongjing; Zeng, Huazong; Cai, Wangwei

    2016-01-01

    Favism is a life-threatening hemolytic anemia resulting from the intake of fava beans by susceptible individuals with low erythrocytic glucose 6-phosphate dehydrogenase (G6PD) activity. However, little is known about the metabolomic changes in plasma and liver after the intake of fava beans in G6PD normal and deficient states. In this study, gas chromatography/mass spectrometry was used to analyze the plasma and liver metabolic alterations underlying the effects of fava beans in C3H- and G6PD-deficient (G6PDx) mice, and to find potential biomarkers and metabolic changes associated with favism. Our results showed that fava beans induced oxidative stress in both C3H and G6PDx mice. Significantly, metabolomic differences were observed in plasma and liver between the control and fava bean treated groups of both C3H and G6PDx mice. The levels of 7 and 21 metabolites in plasma showed significant differences between C3H-control (C3H-C)- and C3H fava beans-treated (C3H-FB) mice, and G6PDx-control (G6PDx-C)- and G6PDx fava beans-treated (G6PDx-FB) mice, respectively. Similarly, the levels of 7 and 25 metabolites in the liver showed significant differences between C3H and C3H-FB, and G6PDx and G6PDx-FB, respectively. The levels of oleic acid, linoleic acid, and creatinine were significantly increased in the plasma of both C3H-FB and G6PDx-FB mice. In the liver, more metabolic alterations were observed in G6PDx-FB mice than in C3H-FB mice, and were involved in a sugar, fatty acids, amino acids, cholesterol biosynthesis, the urea cycle, and the nucleotide metabolic pathway. These findings suggest that oleic acid, linoleic acid, and creatinine may be potential biomarkers of the response to fava beans in C3H and G6PDx mice and therefore that oleic acid and linoleic acid may be involved in oxidative stress induced by fava beans. This study demonstrates that G6PD activity in mice can affect their metabolic pathways in response to fava beans.

  20. Gas Chromatography/Mass Spectrometry-Based Metabolomic Profiling Reveals Alterations in Mouse Plasma and Liver in Response to Fava Beans.

    Directory of Open Access Journals (Sweden)

    Man Xiao

    Full Text Available Favism is a life-threatening hemolytic anemia resulting from the intake of fava beans by susceptible individuals with low erythrocytic glucose 6-phosphate dehydrogenase (G6PD activity. However, little is known about the metabolomic changes in plasma and liver after the intake of fava beans in G6PD normal and deficient states. In this study, gas chromatography/mass spectrometry was used to analyze the plasma and liver metabolic alterations underlying the effects of fava beans in C3H- and G6PD-deficient (G6PDx mice, and to find potential biomarkers and metabolic changes associated with favism. Our results showed that fava beans induced oxidative stress in both C3H and G6PDx mice. Significantly, metabolomic differences were observed in plasma and liver between the control and fava bean treated groups of both C3H and G6PDx mice. The levels of 7 and 21 metabolites in plasma showed significant differences between C3H-control (C3H-C- and C3H fava beans-treated (C3H-FB mice, and G6PDx-control (G6PDx-C- and G6PDx fava beans-treated (G6PDx-FB mice, respectively. Similarly, the levels of 7 and 25 metabolites in the liver showed significant differences between C3H and C3H-FB, and G6PDx and G6PDx-FB, respectively. The levels of oleic acid, linoleic acid, and creatinine were significantly increased in the plasma of both C3H-FB and G6PDx-FB mice. In the liver, more metabolic alterations were observed in G6PDx-FB mice than in C3H-FB mice, and were involved in a sugar, fatty acids, amino acids, cholesterol biosynthesis, the urea cycle, and the nucleotide metabolic pathway. These findings suggest that oleic acid, linoleic acid, and creatinine may be potential biomarkers of the response to fava beans in C3H and G6PDx mice and therefore that oleic acid and linoleic acid may be involved in oxidative stress induced by fava beans. This study demonstrates that G6PD activity in mice can affect their metabolic pathways in response to fava beans.

  1. Development of a high performance liquid chromatography tandem mass spectrometry based analysis for the simultaneous quantification of various Alternaria toxins in wine, vegetable juices and fruit juices.

    Science.gov (United States)

    Zwickel, Theresa; Klaffke, Horst; Richards, Keith; Rychlik, Michael

    2016-07-15

    An analytical method based on high performance liquid chromatography (HPLC) and tandem mass spectrometry (MS/MS) detection for the simultaneous quantification of 12 Alternaria toxins in wine, vegetable juices and fruit juices was developed. Excellent chromatographic performance was demonstrated for tenuazonic acid (TeA) in a multi-analyte method. This comprehensive study is also the first to report the determination of TeA, alternariol (AOH), alternariol monomethyl ether (AME), tentoxin (TEN) and altenuene (ALT), altertoxin I (ATX-I), altertoxin II (ATX-II), altenuisol (ATL), iso-altenuene (isoALT), altenuic acid III (AA-III) and the AAL toxins TB1 und TB2 in samples from the German market. Several types of HPLC columns were tested for the liquid chromatographic separation of the toxins of interest that widely differ in their polarities. The focus was on gaining suitable retention while avoiding derivatization steps especially for TeA and AA-III. Three atmospheric pressure ionization techniques used with liquid chromatography (electrospray, chemical and photo ionization) were tested to obtain the best selectivity and sensitivity. Samples were diluted with sodium hydrogen carbonate buffer and extracted on a diatomaceous earth solid phase extraction cartridge. Method validation was carried out by using tomato juice, citrus juice and white wine as blank matrices. Limits of detection ranged from 0.10 to 0.59μgL(-1) and limits of quantification ranged from 0.4-3.1μgL(-1) depending on the toxin and matrix. Recoveries were around 100±9% for all toxins except stemphyltoxin III (STTX-III) and altenusin (ALS) due to instability during sample clean up. Matrix-induced effects leading to ion suppression especially for ATX-I, ATX-II and AA-III were investigated. Relative standard deviations of repeatability (RSDr) and intermediate reproducibility (RSDR) were ≤9.3 and ≤17.1, respectively, for the toxins in different matrices at levels of 5 and 30μgL(-1). Finally, 103

  2. Fast and efficient proteolysis by reusable pepsin-encapsulated magnetic sol-gel material for mass spectrometry-based proteomics applications.

    Science.gov (United States)

    Kayili, H Mehmet; Salih, Bekir

    2016-08-01

    Hydrophobic silicon-based material having magnetic properties was fairly synthesized by a classical sol-gel approach. Pepsin enzyme was encapsulated in the sol-gel material and the enzyme activity was evaluated in consequence of the digestion of some common proteins such as α- and β-casein, cytochrome c, myoglobin, and bovine serum albumin (BSA) both in a single protein batch and in the protein mixture. The optimum digestion time of the studied proteins using pepsin-encapsulated magnetic sol-gel material was found to be 20min. To produce the magnetic sol-gel material for convenient and easy proteomics applications, Fe3O4 was doped inside sol-gel material during the gelation step. It was observed that the activity of encapsulated pepsin was not affected by the amount of Fe3O4. Poly(ethylene glycol) was also inserted in sol-gel bulk to obtain suitable roughness and increase the hydrophilicity of the material surface to let protein molecules reach to the sol-gel material easily. The digestion of the protein mixture and non-fat bovine milk was performed with the pepsin-encapsulated magnetic sol-gel material and the digested solutions were analyzed using SDS-PAGE, MALDI-TOF-MS and LC-MS/MS for the protein identification. Reusability of the pepsin-encapsulated sol-gel material was examined and it was determined that they could be used at least 20 times. Finally, IgG digestions with a fast incubation time period were carried out using pepsin-encapsulated sol-gel material for generation of (Fab)2 product to evaluate the kinetic performance of the material. Copyright © 2016 Elsevier B.V. All rights reserved.

  3. Comparison of simple extraction procedures in liquid chromatography-mass spectrometry based determination of serum 7α-hydroxy-4-cholesten-3-one, a surrogate marker of bile acid synthesis.

    Science.gov (United States)

    LeníĿek, Martin; Vecka, Marek; Žížalová, Kateſina; Vítek, Libor

    2016-10-15

    The serum concentration of 7α-hydroxy-4-cholesten-3-one (C4), a marker of cholesterol 7α-hydroxylase activity, has recently become an attractive diagnostic tool for researchers interested in cholesterol and bile acid metabolism. The rapidly increasing demand of C4 measurement led to the development of various fast, mostly mass spectrometry-based analytical methods. Our aim was to compare four simple (i.e., not requiring solid phase extraction) extraction procedures (two "one-phase", and two "two-phase") in terms of basic analytical performance and their labouriousness. All methods exhibited comparable extraction recoveries (ranging from 88 to 97%) and intra-assay precision (variation coefficients below 10%), and failed in the removal of phospholipids. Although marked differences were observed in desalting and deproteination, all methods can be considered satisfactory. Simple acetonitrile precipitation can be recommended if a fast extraction and minimal hands-on time is preferred; while two-phase ammonium sulphate:acetonitrile extraction should be chosen when maximal deproteination is required. Copyright © 2016 Elsevier B.V. All rights reserved.

  4. Determination of bovine lactoferrin in dairy products by ultra-high performance liquid chromatography–tandem mass spectrometry based on tryptic signature peptides employing an isotope-labeled winged peptide as internal standard

    International Nuclear Information System (INIS)

    Zhang, Jingshun; Lai, Shiyun; Cai, Zengxuan; Chen, Qi; Huang, Baifen; Ren, Yiping

    2014-01-01

    Highlights: • A UHPLC–MS/MS method for quantification of bovine lactoferrin was developed. • Tryptic fragment LRPVAAEIYGTK was chosen as signature peptide of bovine lactoferrin. • A winged peptide containing isotopically-labeled signature peptide was designed as internal standard. • The method for determining lactoferrin does not discriminate between the different forms of lactoferrin. • Meet the growing demand to quantify bovine lactoferrin in different dairy products. - Abstract: A new and sensitive determination method was developed for bovine lactoferrin in dairy products including infant formulas based on the signature peptide by ultra high-performance liquid chromatography and triple-quadrupole tandem mass spectrometry under the multiple reaction monitoring mode. The simple pretreatment procedures included the addition of a winged peptide containing the isotope-labeled signature peptide as internal standard, followed by an enzymatic digestion with trypsin. The signature peptide was chosen and identified from the tryptic hydrolyzates of bovine lactoferrin by ultra high-performance liquid chromatography and quadrupole-time-of-flight tandem mass spectrometry based on sequence database search. Analytes were separated on an ACQUITY UPLC BEH 300 C18 column and monitored by MS/MS in seven minutes. Quantitative result bias due to matrix effect and tryptic efficiency was corrected through the use of synthetic isotope-labeled standards. The limit of detection and limit of quantification were 0.3 mg/100 g and 1.0 mg/100 g, respectively. Bovine lactoferrin within the concentration range of 10–1000 nmol L −1 showed a strong linear relationship with a linear correlation coefficient (r) of >0.998. The intra- and inter-day precision of the method were RSD < 6.5% and RSD < 7.1%, respectively. Excellent repeatability (RSD < 6.4%) substantially supported the application of this method for the determination of bovine lactoferrin in dairy samples. The present

  5. Determination of bovine lactoferrin in dairy products by ultra-high performance liquid chromatography–tandem mass spectrometry based on tryptic signature peptides employing an isotope-labeled winged peptide as internal standard

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Jingshun [Zhejiang Provincial Center for Disease Control and Prevention, Hangzhou 310051 (China); Lai, Shiyun [Beingmate Research Institute, Beingmate Baby and Child Food Co., Ltd., Hangzhou 310007 (China); Cai, Zengxuan [Zhejiang Provincial Center for Disease Control and Prevention, Hangzhou 310051 (China); Chen, Qi [Beingmate Research Institute, Beingmate Baby and Child Food Co., Ltd., Hangzhou 310007 (China); Huang, Baifen [Zhejiang Provincial Center for Disease Control and Prevention, Hangzhou 310051 (China); Ren, Yiping, E-mail: renyiping@263.net [Zhejiang Provincial Center for Disease Control and Prevention, Hangzhou 310051 (China)

    2014-06-01

    Highlights: • A UHPLC–MS/MS method for quantification of bovine lactoferrin was developed. • Tryptic fragment LRPVAAEIYGTK was chosen as signature peptide of bovine lactoferrin. • A winged peptide containing isotopically-labeled signature peptide was designed as internal standard. • The method for determining lactoferrin does not discriminate between the different forms of lactoferrin. • Meet the growing demand to quantify bovine lactoferrin in different dairy products. Abstract: A new and sensitive determination method was developed for bovine lactoferrin in dairy products including infant formulas based on the signature peptide by ultra high-performance liquid chromatography and triple-quadrupole tandem mass spectrometry under the multiple reaction monitoring mode. The simple pretreatment procedures included the addition of a winged peptide containing the isotope-labeled signature peptide as internal standard, followed by an enzymatic digestion with trypsin. The signature peptide was chosen and identified from the tryptic hydrolyzates of bovine lactoferrin by ultra high-performance liquid chromatography and quadrupole-time-of-flight tandem mass spectrometry based on sequence database search. Analytes were separated on an ACQUITY UPLC BEH 300 C18 column and monitored by MS/MS in seven minutes. Quantitative result bias due to matrix effect and tryptic efficiency was corrected through the use of synthetic isotope-labeled standards. The limit of detection and limit of quantification were 0.3 mg/100 g and 1.0 mg/100 g, respectively. Bovine lactoferrin within the concentration range of 10–1000 nmol L⁻¹ showed a strong linear relationship with a linear correlation coefficient (r) of >0.998. The intra- and inter-day precision of the method were RSD < 6.5% and RSD < 7.1%, respectively. Excellent repeatability (RSD < 6.4%) substantially supported the application of this method for the determination of bovine lactoferrin in dairy samples. The present method

  6. Screening of 439 Pesticide Residues in Fruits and Vegetables by Gas Chromatography-Quadrupole-Time-of-Flight Mass Spectrometry Based on TOF Accurate Mass Database and Q-TOF Spectrum Library.

    Science.gov (United States)

    Li, Jian-Xun; Li, Xiao-Ying; Chang, Qiao-Ying; Li, Yan; Jin, Ling-He; Pang, Guo-Fang; Fan, Chun-Lin

    2018-05-03

    Because of its unique characteristics of accurate mass full-spectrum acquisition, high resolution, and fast acquisition rates, GC-quadrupole-time-of-flight MS (GC-Q-TOF/MS) has become a powerful tool for pesticide residue analysis. In this study, a TOF accurate mass database and Q-TOF spectrum library of 439 pesticides were established, and the parameters of the TOF database were optimized. Through solid-phase extraction (SPE), whereby pesticides are extracted from fruit and vegetable substrates by using 40 mL 1% acetic acid in acetonitrile (v/v), purified by the Carbon/NH₂ SPE cartridge, and finally detected by GC-Q-TOF/MS, the rapid analysis of 439 pesticides in fruits and vegetables can be achieved. The methodology verification results show that more than 70 and 91% of pesticides, spiked in fruits and vegetables with concentrations of 10 and 100 μg/kg, respectively, saw recoveries that conform to the European Commission's criterion of between 70 and 120% with RSD ≤20%. Eighty-one percent of pesticides have screening detection limits lower than 10 μg/kg, which makes this a reliable analysis technology for the monitoring of pesticide residues in fruits and vegetables. This technology was further validated for its characteristics of high precision, high speed, and high throughput through successful detection of 9817 samples during 2013-2015.

  7. Screening of 485 Pesticide Residues in Fruits and Vegetables by Liquid Chromatography-Quadrupole-Time-of-Flight Mass Spectrometry Based on TOF Accurate Mass Database and QTOF Spectrum Library.

    Science.gov (United States)

    Pang, Guo-Fang; Fan, Chun-Lin; Chang, Qiao-Ying; Li, Jian-Xun; Kang, Jian; Lu, Mei-Ling

    2018-03-22

    This paper uses the LC-quadrupole-time-of-flight MS technique to evaluate the behavioral characteristics of MSof 485 pesticides under different conditions and has developed an accurate mass database and spectra library. A high-throughput screening and confirmation method has been developed for the 485 pesticides in fruits and vegetables. Through the optimization of parameters such as accurate mass number, time of retention window, ionization forms, etc., the method has improved the accuracy of pesticide screening, thus avoiding the occurrence of false-positive and false-negative results. The method features a full scan of fragments, with 80% of pesticide qualitative points over 10, which helps increase pesticide qualitative accuracy. The abundant differences of fragment categories help realize the effective separation and qualitative identification of isomer pesticides. Four different fruits and vegetables-apples, grapes, celery, and tomatoes-were chosen to evaluate the efficiency of the method at three fortification levels of 5, 10, and 20 μg/kg, and satisfactory results were obtained. With this method, a national survey of pesticide residues was conducted between 2012 and 2015 for 12 551 samples of 146 different fruits and vegetables collected from 638 sampling points in 284 counties across 31 provincial capitals/cities directly under the central government, which provided scientific data backup for ensuring pesticide residue safety of the fruits and vegetables consumed daily by the public. Meanwhile, the big data statistical analysis of the new technique also further proves it to be of high speed, high throughput, high accuracy, high reliability, and high informatization.

  8. Describing the Diapause-Preparatory Proteome of the Beetle Colaphellus bowringi and Identifying Candidates Affecting Lipid Accumulation Using Isobaric Tags for Mass Spectrometry-Based Proteome Quantification (iTRAQ

    Directory of Open Access Journals (Sweden)

    Daniel A. Hahn

    2017-04-01

    Full Text Available Prior to entering diapause, insects must prepare themselves physiologically to withstand the stresses of arresting their development for a lengthy period. While studies describing the biochemical and cellular milieu of the maintenance phase of diapause are accumulating, few studies have taken an “omics” approach to describing molecular events during the diapause preparatory phase. We used isobaric tags and mass spectrometry (iTRAQ to quantitatively compare the expression profiles of proteins identified during the onset of diapause preparation phase in the heads of adult female cabbage beetles, Colaphellus bowringi. A total of 3,175 proteins were identified, 297 of which were differentially expressed between diapause-destined and non-diapause-destined female adults and could therefore be involved in diapause preparation in this species. Comparison of identified proteins with protein function databases shows that many of these differentially expressed proteins enhanced in diapause destined beetles are involved in energy production and conversion, carbohydrate metabolism and transport, and lipid metabolism. Further hand annotation of differentially abundant peptides nominates several associated with stress hardiness, including HSPs and antioxidants, as well as neural development. In contrast, non-diapause destined beetles show substantial increases in cuticle proteins, suggesting additional post-emergence growth. Using RNA interference to silence a fatty acid-binding protein (FABP that was highly abundant in the head of diapause-destined females prevented the accumulation of lipids in the fat body, a common product of diapause preparation in this species and others. Surprisingly, RNAi against the FABP also affected the transcript abundance of several heat shock proteins. These results suggest that the identified differentially expressed proteins that play vital roles in lipid metabolism may also contribute somehow to enhanced hardiness to

  9. A mass spectrometry-based proteomic approach for identification of serine/threonine-phosphorylated proteins by enrichment with phospho-specific antibodies

    DEFF Research Database (Denmark)

    Grønborg, Mads; Kristiansen, Troels Zakarias; Stensballe, Allan

    2002-01-01

    /threonine-phosphorylated proteins including drebrin 1, alpha-actinin 4, and filamin-1. We also identified a protein, poly(A)-binding protein 2, which was previously not known to be phosphorylated, in addition to a novel protein without any obvious domains that we designate as Frigg. Frigg is widely expressed and was demonstrated...

  10. Application of ultraperformance liquid chromatography/mass spectrometry-based metabonomic techniques to analyze the joint toxic action of long-term low-level exposure to a mixture of organophosphate pesticides on rat urine profile.

    Science.gov (United States)

    Du, Longfei; Wang, Hong; Xu, Wei; Zeng, Yan; Hou, Yurong; Zhang, Yuqiu; Zhao, Xiujuan; Sun, Changhao

    2013-07-01

    In previously published articles, we evaluated the toxicity of four organophosphate (OP) pesticides (dichlorvos, dimethoate, acephate, and phorate) to rats using metabonomic technology at their corresponding no observed adverse effect level (NOAEL). Results show that a single pesticide elicits no toxic response. This study aimed to determine whether chronic exposure to a mixture of the above four pesticides (at their corresponding NOAEL) can lead to joint toxic action in rats using the same technology. Pesticides were administered daily to rats through drinking water for 24 weeks. The above mixture of the four pesticides showed joint toxic action at the NOAEL of each pesticide. The metabonomic profiles of rats urine were analyzed by ultraperformance liquid chromatography/mass spectrometry. The 16 metabolites statistically significantly changed in all treated groups compared with the control group. Dimethylphosphate and dimethyldithiophosphate exclusively detected in all treated groups can be used as early, sensitive biomarkers for exposure to a mixture of the OP pesticides. Moreover, exposure to the OP pesticides resulted in increased 7-methylguanine, ribothymidine, cholic acid, 4-pyridoxic acid, kynurenine, and indoxyl sulfate levels, as well as decreased hippuric acid, creatinine, uric acid, gentisic acid, C18-dihydrosphingosine, phytosphingosine, suberic acid, and citric acid. The results indicated that a mixture of OP pesticides induced DNA damage and oxidative stress, disturbed the metabolism of lipids, and interfered with the tricarboxylic acid cycle. Ensuring food safety requires not only the toxicology test data of each pesticide for the calculation of the acceptable daily intake but also the joint toxic action.

  11. Genetic, phenotypic and matrix-assisted laser desorption ionization time-of-flight mass spectrometry-based identification of anaerobic bacteria and determination of their antimicrobial susceptibility at a University Hospital in Japan.

    Science.gov (United States)

    Yunoki, Tomoyuki; Matsumura, Yasufumi; Nakano, Satoshi; Kato, Karin; Hotta, Go; Noguchi, Taro; Yamamoto, Masaki; Nagao, Miki; Takakura, Shunji; Ichiyama, Satoshi

    2016-05-01

    The accuracies of matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) and the phenotypic method using VITEK 2 were compared to the accuracy of 16S rRNA sequence analysis for the identification of 170 clinically isolated anaerobes. The antimicrobial susceptibility of the isolates was also evaluated. Genetic analysis identified 21 Gram-positive species in 14 genera and 29 Gram-negative species in 11 genera. The most frequently isolated genera were Prevotella spp. (n = 46), Bacteroides spp. (n = 25) and Clostridium spp. (n = 25). MALDI-TOF MS correctly identified more isolates compared with VITEK 2 at the species (80 vs. 58%, respectively; p anaerobic agents indicated that the isolates of the three most frequently identified anaerobic genera exhibited good antimicrobial susceptibility. Copyright © 2016 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

  12. Validation of an online dual-loop cleanup device with an electrospray ionization tandem mass spectrometry-based system for simultaneous quantitative analysis of urinary benzene exposure biomarkers trans, trans-muconic acid and S-phenylmercapturic acid

    International Nuclear Information System (INIS)

    Lin, L.-C.; Chiung, Y.-M.; Shih, J.-F.; Shih, T.-S.G; Liao, P.-C.

    2006-01-01

    The aim of this study is to validate isotope-dilution electrospray ionization tandem mass spectrometry (ESI-MS-MS) method with a dual-loop cleanup device for simultaneous quantitation of two benzene metabolites, trans, trans-muconic acid (ttMA) and S-phenylmercapturic acid (SPMA), in human urine. In this study, a pooled blank urine matrix from rural residents was adopted for validation of the analytical method. The calibration curve, detection limit, recovery, precision, accuracy and the stability of sample storage for the system have been characterized. Calibration plots of ttMA and SPMA standards spiked into two kinds of urine matrixes over a wide concentration range, 1/32-8-fold biological exposure indices (BEIs) values, showed good linearity (R > 0.9992). The detection limits in pooled urine matrix for ttMA and SPMA were 1.27 and 0.042 μg g -1 creatinine, respectively. For both of ttMA and SPMA, the intra- and inter-day precision values were considered acceptable well below 25% at the various spiked concentrations. The intra- and inter-day apparent recovery values were also considered acceptable (apparent recovery >90%). The ttMA accuracy was estimated by urinary standard reference material (SRM). The accuracy reported in terms of relative error (RE) was 5.0 ± 2.0% (n = 3). The stability of sample storage at 4 or -20 deg. C were assessed. Urinary ttMA and SPMA were found to be stable for at least 8 weeks when stored at 4 or -20 deg. C. In addition, urine samples from different benzene exposure groups were collected and measured in this system. Without tedious manual sample preparation procedure, the analytical system was able to quantify simultaneously ttMA and SPMA in less than 20 min

  13. Development, validation and application of a micro-liquid chromatography-tandem mass spectrometry based method for simultaneous quantification of selected protein biomarkers of endothelial dysfunction in murine plasma.

    Science.gov (United States)

    Suraj, Joanna; Kurpińska, Anna; Olkowicz, Mariola; Niedzielska-Andres, Ewa; Smolik, Magdalena; Zakrzewska, Agnieszka; Jasztal, Agnieszka; Sitek, Barbara; Chlopicki, Stefan; Walczak, Maria

    2018-02-05

    The objective of this study was to develop and validate the method based on micro-liquid chromatography-tandem mass spectrometry (microLC/MS-MRM) for simultaneous determination of adiponectin (ADN), von Willebrand factor (vWF), soluble form of vascular cell adhesion molecule 1 (sVCAM-1), soluble form of intercellular adhesion molecule 1 (sICAM-1) and syndecan-1 (SDC-1) in mouse plasma. The calibration range was established from 2.5pmol/mL to 5000pmol/mL for ADN; 5pmol/mL to 5000pmol/mL for vWF; 0.375pmol/mL to 250pmol/mL for sVCAM-1 and sICAM-1; and 0.25pmol/mL to 250pmol/mL for SDC-1. The method was applied to measure the plasma concentration of selected proteins in mice fed high-fat diet (HFD), and revealed the pro-thrombotic status by increased concentration of vWF (1.31±0.17 nmol/mL (Control) vs 1.98±0.09 nmol/mL (HFD), p <0.05) and the dysregulation of adipose tissue metabolism by decreased concentration of ADN (0.62±0.08 nmol/mL (Control) vs 0.37±0.06 nmol/mL (HFD), p <0.05). In conclusion, the microLC/MS-MRM-based method allows for reliable measurements of selected protein biomarkers of endothelial dysfunction in mouse plasma. Copyright © 2017 Elsevier B.V. All rights reserved.

  14. A rapid matrix-assisted laser desorption ionization-time of flight mass spectrometry-based method for single-plasmid tracking in an outbreak of carbapenem-resistant Enterobacteriaceae.

    Science.gov (United States)

    Lau, Anna F; Wang, Honghui; Weingarten, Rebecca A; Drake, Steven K; Suffredini, Anthony F; Garfield, Mark K; Chen, Yong; Gucek, Marjan; Youn, Jung-Ho; Stock, Frida; Tso, Hanna; DeLeo, Jim; Cimino, James J; Frank, Karen M; Dekker, John P

    2014-08-01

    Carbapenem-resistant Enterobacteriaceae (CRE) have spread globally and represent a serious and growing threat to public health. Rapid methods for tracking plasmids carrying carbapenemase genes could greatly benefit infection control efforts. Here, we demonstrate that real-time, direct tracking of a single plasmid in a bacterial strain responsible for an outbreak is possible using a commercial matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) system. In this case, we retrospectively tracked the bla(KPC) carbapenemase gene-bearing pKpQIL plasmid responsible for a CRE outbreak that occurred at the NIH Clinical Center in 2011. An ∼ 11,109-Da MS peak corresponding to a gene product of the bla(KPC) pKpQIL plasmid was identified and characterized using a combination of proteomics and molecular techniques. This plasmid peak was present in spectra from retrospectively analyzed K. pneumoniae outbreak isolates, concordant with results from whole-genome sequencing, and absent from a diverse control set of bla(KPC)-negative clinical Enterobacteriaceae isolates. Notably, the gene characterized here is located adjacent to the bla(KPC) Tn4401 transposon on the pKpQIL plasmid. Sequence analysis demonstrates the presence of this gene in other bla(KPC) Tn4401-containing plasmids and suggests that this signature MS peak may be useful in tracking other plasmids conferring carbapenem resistance. Plasmid identification using this MALDI-TOF MS method was accomplished in as little as 10 min from isolated colonies and 30 min from positive (spiked) blood cultures, demonstrating the potential clinical utility for real-time plasmid tracking in an outbreak. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

  15. A Rapid Matrix-Assisted Laser Desorption Ionization–Time of Flight Mass Spectrometry-Based Method for Single-Plasmid Tracking in an Outbreak of Carbapenem-Resistant Enterobacteriaceae

    Science.gov (United States)

    Lau, Anna F.; Wang, Honghui; Weingarten, Rebecca A.; Drake, Steven K.; Suffredini, Anthony F.; Garfield, Mark K.; Chen, Yong; Gucek, Marjan; Youn, Jung-Ho; Stock, Frida; Tso, Hanna; DeLeo, Jim; Cimino, James J.; Frank, Karen M.

    2014-01-01

    Carbapenem-resistant Enterobacteriaceae (CRE) have spread globally and represent a serious and growing threat to public health. Rapid methods for tracking plasmids carrying carbapenemase genes could greatly benefit infection control efforts. Here, we demonstrate that real-time, direct tracking of a single plasmid in a bacterial strain responsible for an outbreak is possible using a commercial matrix-assisted laser desorption ionization–time of flight mass spectrometry (MALDI-TOF MS) system. In this case, we retrospectively tracked the blaKPC carbapenemase gene-bearing pKpQIL plasmid responsible for a CRE outbreak that occurred at the NIH Clinical Center in 2011. An ∼11,109-Da MS peak corresponding to a gene product of the blaKPC pKpQIL plasmid was identified and characterized using a combination of proteomics and molecular techniques. This plasmid peak was present in spectra from retrospectively analyzed K. pneumoniae outbreak isolates, concordant with results from whole-genome sequencing, and absent from a diverse control set of blaKPC-negative clinical Enterobacteriaceae isolates. Notably, the gene characterized here is located adjacent to the blaKPC Tn4401 transposon on the pKpQIL plasmid. Sequence analysis demonstrates the presence of this gene in other blaKPC Tn4401-containing plasmids and suggests that this signature MS peak may be useful in tracking other plasmids conferring carbapenem resistance. Plasmid identification using this MALDI-TOF MS method was accomplished in as little as 10 min from isolated colonies and 30 min from positive (spiked) blood cultures, demonstrating the potential clinical utility for real-time plasmid tracking in an outbreak. PMID:24850353

  16. Mass spectrometry based proteomics, background, status and future needs

    DEFF Research Database (Denmark)

    Roepstorff, Peter

    2012-01-01

    An overview of the background for proteomics and a description of the present state of art are given with a description of the main strategies in proteomics. The advantages and limitations of the two major strategies, 2D-gel based and LC-MS based, are discussed and a combination for the two, CeLC...

  17. New approaches for metabolomics by mass spectrometry

    Energy Technology Data Exchange (ETDEWEB)

    Vertes, Akos [George Washington Univ., Washington, DC (United States)

    2017-07-10

    Small molecules constitute a large part of the world around us, including fossil and some renewable energy sources. Solar energy harvested by plants and bacteria is converted into energy rich small molecules on a massive scale. Some of the worst contaminants of the environment and compounds of interest for national security also fall in the category of small molecules. The development of large scale metabolomic analysis methods lags behind the state of the art established for genomics and proteomics. This is commonly attributed to the diversity of molecular classes included in a metabolome. Unlike nucleic acids and proteins, metabolites do not have standard building blocks, and, as a result, their molecular properties exhibit a wide spectrum. This impedes the development of dedicated separation and spectroscopic methods. Mass spectrometry (MS) is a strong contender in the quest for a quantitative analytical tool with extensive metabolite coverage. Although various MS-based techniques are emerging for metabolomics, many of these approaches include extensive sample preparation that make large scale studies resource intensive and slow. New ionization methods are redefining the range of analytical problems that can be solved using MS. This project developed new approaches for the direct analysis of small molecules in unprocessed samples, as well as pushed the limits of ultratrace analysis in volume limited complex samples. The projects resulted in techniques that enabled metabolomics investigations with enhanced molecular coverage, as well as the study of cellular response to stimuli on a single cell level. Effectively individual cells became reaction vessels, where we followed the response of a complex biological system to external perturbation. We established two new analytical platforms for the direct study of metabolic changes in cells and tissues following external perturbation. For this purpose we developed a novel technique, laser ablation electrospray

  18. Multiple diagnostic approaches to palpable breast mass

    Energy Technology Data Exchange (ETDEWEB)

    Chin, Soo Yil; Kim, Kie Hwan; Moon, Nan Mo; Kim, Yong Kyu; Jang, Ja June [Korea Cancer Center Hospital, Seoul (Korea, Republic of)

    1985-12-15

    The combination of the various diagnostic methods of palpable breast mass has improved the diagnostic accuracy. From September 1983 to August 1985 pathologically proven 85 patients with palpable breast masses examined with x-ray mammography, ultrasonography, penumomammography and aspiration cytology at Korea Cancer Center Hospital were analyzed. The diagnostic accuracies of each methods were 77.6% of mammogram, 74.1% of ultrasonogram, 90.5% of penumomammogram and 92.4% of aspiration cytology. Pneumomammograms was accomplished without difficulty or complication and depicted more clearly delineated mass with various pathognomonic findings; air-ductal pattern in fibroadenoma (90.4%) and cystosarcoma phylloides (100%), air-halo in fibrocystic disease (14.2%), fibroadenoma (100%), cystosarcoma phylloides (100%), air-cystogram in cystic type of fibrocystic disease (100%) and vaculoar pattern or irregular air collection without retained peripheral gas in carcinoma.

  19. Multiple diagnostic approaches to palpable breast mass

    International Nuclear Information System (INIS)

    Chin, Soo Yil; Kim, Kie Hwan; Moon, Nan Mo; Kim, Yong Kyu; Jang, Ja June

    1985-01-01

    The combination of the various diagnostic methods of palpable breast mass has improved the diagnostic accuracy. From September 1983 to August 1985 pathologically proven 85 patients with palpable breast masses examined with x-ray mammography, ultrasonography, penumomammography and aspiration cytology at Korea Cancer Center Hospital were analyzed. The diagnostic accuracies of each methods were 77.6% of mammogram, 74.1% of ultrasonogram, 90.5% of penumomammogram and 92.4% of aspiration cytology. Pneumomammograms was accomplished without difficulty or complication and depicted more clearly delineated mass with various pathognomonic findings; air-ductal pattern in fibroadenoma (90.4%) and cystosarcoma phylloides (100%), air-halo in fibrocystic disease (14.2%), fibroadenoma (100%), cystosarcoma phylloides (100%), air-cystogram in cystic type of fibrocystic disease (100%) and vaculoar pattern or irregular air collection without retained peripheral gas in carcinoma

  20. Review: Management of adnexal masses: An age-guided approach ...

    African Journals Online (AJOL)

    Adnexal masses in different age groups may need different management approaches. By elimination of the type of mass that is less likely in a specific age group one can identify the most prevalent group which can guide management. Most important of all, the probability of malignancy must either be identified or ruled out.

  1. Mass spectrometry in life science research.

    Science.gov (United States)

    Lehr, Stefan; Markgraf, Daniel

    2016-12-01

    Investigating complex signatures of biomolecules by mass spectrometry approaches has become indispensable in molecular life science research. Nowadays, various mass spectrometry-based omics technologies are available to monitor qualitative and quantitative changes within hundreds or thousands of biological active components, including proteins/peptides, lipids and metabolites. These comprehensive investigations have the potential to decipher the pathophysiology of disease development at a molecular level and to monitor the individual response of pharmacological treatment or lifestyle intervention.

  2. Mass-spectrometry analysis of histone post-translational modifications in pathology tissue using the PAT-H-MS approach

    Directory of Open Access Journals (Sweden)

    Roberta Noberini

    2016-06-01

    Full Text Available Aberrant histone post-translational modifications (hPTMs have been implicated with various pathologies, including cancer, and may represent useful epigenetic biomarkers. The data described here provide a mass spectrometry-based quantitative analysis of hPTMs from formalin-fixed paraffin-embedded (FFPE tissues, from which histones were extracted through the recently developed PAT-H-MS method. First, we analyzed FFPE samples from mouse spleen and liver or human breast cancer up to six years old, together with their corresponding fresh frozen tissue. We then combined the PAT-H-MS approach with a histone-focused version of the super-SILAC strategy-using a mix of histones from four breast cancer cell lines as a spike-in standard- to accurately quantify hPTMs from breast cancer specimens belonging to different subtypes. The data, which are associated with a recent publication (Pathology tissue-quantitative mass spectrometry analysis to profile histone post-translational modification patterns in patient samples (Noberini, 2015 [1], are deposited at the ProteomeXchange Consortium via the PRIDE partner repository with the dataset identifier http://www.ebi.ac.uk/pride/archive/projects/PXD002669.

  3. Amputations in natural disasters and mass casualties: staged approach.

    Science.gov (United States)

    Wolfson, Nikolaj

    2012-10-01

    Amputation is a commonly performed procedure during natural disasters and mass casualties related to industrial accidents and military conflicts where large civilian populations are subjected to severe musculoskeletal trauma. Crush injuries and crush syndrome, an often-overwhelming number of casualties, delayed presentations, regional cultural and other factors, all can mandate a surgical approach to amputation that is different than that typically used under non-disaster conditions. The following article will review the subject of amputation during natural disasters and mass casualties with emphasis on a staged approach to minimise post-surgical complications, especially infection.

  4. An approach to the neck mass | Thandar | Continuing Medical ...

    African Journals Online (AJOL)

    An approach to the neck mass. MA Thandar, NE Jonas. Abstract. No Abstract. Full Text: EMAIL FREE FULL TEXT EMAIL FREE FULL TEXT · DOWNLOAD FULL TEXT DOWNLOAD FULL TEXT · AJOL African Journals Online. HOW TO USE AJOL... for Researchers · for Librarians · for Authors · FAQ's · More about AJOL ...

  5. Model-Based Systems Engineering Approach to Managing Mass Margin

    Science.gov (United States)

    Chung, Seung H.; Bayer, Todd J.; Cole, Bjorn; Cooke, Brian; Dekens, Frank; Delp, Christopher; Lam, Doris

    2012-01-01

    When designing a flight system from concept through implementation, one of the fundamental systems engineering tasks ismanaging the mass margin and a mass equipment list (MEL) of the flight system. While generating a MEL and computing a mass margin is conceptually a trivial task, maintaining consistent and correct MELs and mass margins can be challenging due to the current practices of maintaining duplicate information in various forms, such as diagrams and tables, and in various media, such as files and emails. We have overcome this challenge through a model-based systems engineering (MBSE) approach within which we allow only a single-source-of-truth. In this paper we describe the modeling patternsused to capture the single-source-of-truth and the views that have been developed for the Europa Habitability Mission (EHM) project, a mission concept study, at the Jet Propulsion Laboratory (JPL).

  6. Endoscopic endonasal approach for mass resection of the pterygopalatine fossa

    Directory of Open Access Journals (Sweden)

    Jan Plzák

    Full Text Available OBJECTIVES: Access to the pterygopalatine fossa is very difficult due to its complex anatomy. Therefore, an open approach is traditionally used, but morbidity is unavoidable. To overcome this problem, an endoscopic endonasal approach was developed as a minimally invasive procedure. The surgical aim of the present study was to evaluate the utility of the endoscopic endonasal approach for the management of both benign and malignant tumors of the pterygopalatine fossa. METHOD: We report our experience with the endoscopic endonasal approach for the management of both benign and malignant tumors and summarize recent recommendations. A total of 13 patients underwent surgery via the endoscopic endonasal approach for pterygopalatine fossa masses from 2014 to 2016. This case group consisted of 12 benign tumors (10 juvenile nasopharyngeal angiofibromas and two schwannomas and one malignant tumor. RESULTS: No recurrent tumor developed during the follow-up period. One residual tumor (juvenile nasopharyngeal angiofibroma that remained in the cavernous sinus was stable. There were no significant complications. Typical sequelae included hypesthesia of the maxillary nerve, trismus, and dry eye syndrome. CONCLUSION: The low frequency of complications together with the high efficacy of resection support the use of the endoscopic endonasal approach as a feasible, safe, and beneficial technique for the management of masses in the pterygopalatine fossa.

  7. Endoscopic endonasal approach for mass resection of the pterygopalatine fossa

    Science.gov (United States)

    Plzák, Jan; Kratochvil, Vít; Kešner, Adam; Šurda, Pavol; Vlasák, Aleš; Zvěřina, Eduard

    2017-01-01

    OBJECTIVES: Access to the pterygopalatine fossa is very difficult due to its complex anatomy. Therefore, an open approach is traditionally used, but morbidity is unavoidable. To overcome this problem, an endoscopic endonasal approach was developed as a minimally invasive procedure. The surgical aim of the present study was to evaluate the utility of the endoscopic endonasal approach for the management of both benign and malignant tumors of the pterygopalatine fossa. METHOD: We report our experience with the endoscopic endonasal approach for the management of both benign and malignant tumors and summarize recent recommendations. A total of 13 patients underwent surgery via the endoscopic endonasal approach for pterygopalatine fossa masses from 2014 to 2016. This case group consisted of 12 benign tumors (10 juvenile nasopharyngeal angiofibromas and two schwannomas) and one malignant tumor. RESULTS: No recurrent tumor developed during the follow-up period. One residual tumor (juvenile nasopharyngeal angiofibroma) that remained in the cavernous sinus was stable. There were no significant complications. Typical sequelae included hypesthesia of the maxillary nerve, trismus, and dry eye syndrome. CONCLUSION: The low frequency of complications together with the high efficacy of resection support the use of the endoscopic endonasal approach as a feasible, safe, and beneficial technique for the management of masses in the pterygopalatine fossa. PMID:29069259

  8. Thomas-Fermi approach to nuclear mass formula. Pt. 1

    International Nuclear Information System (INIS)

    Dutta, A.K.; Arcoragi, J.P.; Pearson, J.M.; Tondeur, F.

    1986-01-01

    With a view to having a more secure basis for the nuclear mass formula than is provided by the drop(let) model, we make a preliminary study of the possibilities offered by the Skyrme-ETF method. Two ways of incorporating shell effects are considered: the ''Strutinsky-integral'' method of Chu et al., and the ''expectation-value'' method of Brack et al. Each of these methods is compared with the HF method in an attempt to see how reliably they extrapolate from the known region of the nuclear chart out to the neutron-drip line. The Strutinsky-integral method is shown to perform particularly well, and to offer a promising approach to a more reliable mass formula. (orig.)

  9. Variational approach to thermal masses in compactified models

    Energy Technology Data Exchange (ETDEWEB)

    Dominici, Daniele [Dipartimento di Fisica e Astronomia Università di Firenze and INFN - Sezione di Firenze,Via G. Sansone 1, 50019 Sesto Fiorentino (Italy); Roditi, Itzhak [Centro Brasileiro de Pesquisas Físicas - CBPF/MCT,Rua Dr. Xavier Sigaud 150, 22290-180, Rio de Janeiro, RJ (Brazil)

    2015-08-20

    We investigate by means of a variational approach the effective potential of a 5DU(1) scalar model at finite temperature and compactified on S{sup 1} and S{sup 1}/Z{sub 2} as well as the corresponding 4D model obtained through a trivial dimensional reduction. We are particularly interested in the behavior of the thermal masses of the scalar field with respect to the Wilson line phase and the results obtained are compared with those coming from a one-loop effective potential calculation. We also explore the nature of the phase transition.

  10. Differential population synthesis approach to mass segregation in M92

    International Nuclear Information System (INIS)

    Tobin, W.J.

    1979-01-01

    Spectra are presented of 26 low-metal stars and of the center and one-quarter intensity positions of M92. Spectral coverage is from 390 to 870 nm with resolution better than 1 nm in the blue and 2 nm in the red. Individual pixel signal-to-noise is about 100. Dwarf features are notably absent from the M92 spectra. Numerical estimates of 36 absorption features are extracted from every spectrum, as are two continuum indices. Mathematical models are constructed describing each feature's dependence on stellar color, luminosity, and metal content and then used to estimate the metal content of 6 of the stars for which the metal content is not known. For 10 features reliably measured in M92's center and edge a mass segregation sensitivity parameter is derived from each feature's deduced luminosity dependence. The ratio of feature equivalent widths at cluster edge and center are compared to this sensitivity: no convincing evidence of mass segregation is seen. The only possible edge-to-center difference seen is in the Mg b 517.4 nm feature. Three of the 10 cluster features can be of interstellar origin, at least in part; in particular the luminosity-sensitive Na D line cannot be used as a segregation indicator. The experience gained suggests that an integrated spectrum approach to globular cluster mass segregation is very difficult. An appendix describes in detail the capabilities of the Pine Bluff Observatory .91 m telescope, Cassegrain grating spectrograph, and intensified Reticon dual diode-array detector. It is possible to determine a highly consistent wavelength calibration

  11. Research of connection between mass audience and new media. Approaches to new model of mass communication measurement

    OpenAIRE

    Sibiriakova Olena Oleksandrivna

    2015-01-01

    In this research the author examines changes to approaches of observation of mass communication. As a result of systemization of key theoretical models of communication, the author comes to conclusion of evolution of ideas about the process of mass communication measurement from linear to multisided and multiple.

  12. Mass Society/Culture/Media: An Eclectic Approach.

    Science.gov (United States)

    Clavner, Jerry B.

    Instructors of courses in mass society, culture, and communication start out facing three types of difficulties: the historical orientation of learning, the parochialism of various disciplines, and negative intellectually elitist attitudes toward mass culture/media. Added to these problems is the fact that many instructors have little or no…

  13. Identification of a novel immunoreceptor tyrosine-based activation motif-containing molecule, STAM2, by mass spectrometry and its involvement in growth factor and cytokine receptor signaling pathways

    DEFF Research Database (Denmark)

    Pandey, A; Fernandez, M M; Steen, H

    2000-01-01

    In an effort to clone novel tyrosine-phosphorylated substrates of the epidermal growth factor receptor, we have initiated an approach coupling affinity purification using anti-phosphotyrosine antibodies to mass spectrometry-based identification. Here, we report the identification of a signaling m...

  14. Neutrino Mass Matrix Textures: A Data-driven Approach

    CERN Document Server

    Bertuzzo, E; Machado, P A N

    2013-01-01

    We analyze the neutrino mass matrix entries and their correlations in a probabilistic fashion, constructing probability distribution functions using the latest results from neutrino oscillation fits. Two cases are considered: the standard three neutrino scenario as well as the inclusion of a new sterile neutrino that potentially explains the reactor and gallium anomalies. We discuss the current limits and future perspectives on the mass matrix elements that can be useful for model building.

  15. On a mass independent approach leading to planetary orbit discretization

    International Nuclear Information System (INIS)

    Oliveira Neto, Marcal de

    2007-01-01

    The present article discusses a possible fractal approach for understanding orbit configurations around a central force field in well known systems of our infinitely small and infinitely large universes, based on quantum atomic models. This approach is supported by recent important theoretical investigations reported in the literature. An application presents a study involving the three star system HD 188753 Cygni in an approach similar to that employed in molecular quantum mechanics investigations

  16. Mass spectrometry imaging enriches biomarker discovery approaches with candidate mapping.

    Science.gov (United States)

    Scott, Alison J; Jones, Jace W; Orschell, Christie M; MacVittie, Thomas J; Kane, Maureen A; Ernst, Robert K

    2014-01-01

    Integral to the characterization of radiation-induced tissue damage is the identification of unique biomarkers. Biomarker discovery is a challenging and complex endeavor requiring both sophisticated experimental design and accessible technology. The resources within the National Institute of Allergy and Infectious Diseases (NIAID)-sponsored Consortium, Medical Countermeasures Against Radiological Threats (MCART), allow for leveraging robust animal models with novel molecular imaging techniques. One such imaging technique, MALDI (matrix-assisted laser desorption ionization) mass spectrometry imaging (MSI), allows for the direct spatial visualization of lipids, proteins, small molecules, and drugs/drug metabolites-or biomarkers-in an unbiased manner. MALDI-MSI acquires mass spectra directly from an intact tissue slice in discrete locations across an x, y grid that are then rendered into a spatial distribution map composed of ion mass and intensity. The unique mass signals can be plotted to generate a spatial map of biomarkers that reflects pathology and molecular events. The crucial unanswered questions that can be addressed with MALDI-MSI include identification of biomarkers for radiation damage that reflect the response to radiation dose over time and the efficacy of therapeutic interventions. Techniques in MALDI-MSI also enable integration of biomarker identification among diverse animal models. Analysis of early, sublethally irradiated tissue injury samples from diverse mouse tissues (lung and ileum) shows membrane phospholipid signatures correlated with histological features of these unique tissues. This paper will discuss the application of MALDI-MSI for use in a larger biomarker discovery pipeline.

  17. Constraining East Antarctic mass trends using a Bayesian inference approach

    Science.gov (United States)

    Martin-Español, Alba; Bamber, Jonathan L.

    2016-04-01

    East Antarctica is an order of magnitude larger than its western neighbour and the Greenland ice sheet. It has the greatest potential to contribute to sea level rise of any source, including non-glacial contributors. It is, however, the most challenging ice mass to constrain because of a range of factors including the relative paucity of in-situ observations and the poor signal to noise ratio of Earth Observation data such as satellite altimetry and gravimetry. A recent study using satellite radar and laser altimetry (Zwally et al. 2015) concluded that the East Antarctic Ice Sheet (EAIS) had been accumulating mass at a rate of 136±28 Gt/yr for the period 2003-08. Here, we use a Bayesian hierarchical model, which has been tested on, and applied to, the whole of Antarctica, to investigate the impact of different assumptions regarding the origin of elevation changes of the EAIS. We combined GRACE, satellite laser and radar altimeter data and GPS measurements to solve simultaneously for surface processes (primarily surface mass balance, SMB), ice dynamics and glacio-isostatic adjustment over the period 2003-13. The hierarchical model partitions mass trends between SMB and ice dynamics based on physical principles and measures of statistical likelihood. Without imposing the division between these processes, the model apportions about a third of the mass trend to ice dynamics, +18 Gt/yr, and two thirds, +39 Gt/yr, to SMB. The total mass trend for that period for the EAIS was 57±20 Gt/yr. Over the period 2003-08, we obtain an ice dynamic trend of 12 Gt/yr and a SMB trend of 15 Gt/yr, with a total mass trend of 27 Gt/yr. We then imposed the condition that the surface mass balance is tightly constrained by the regional climate model RACMO2.3 and allowed height changes due to ice dynamics to occur in areas of low surface velocities (solution that satisfies all the input data, given these constraints. By imposing these conditions, over the period 2003-13 we obtained a mass

  18. Computer-aided detection of masses in digital tomosynthesis mammography: Comparison of three approaches

    International Nuclear Information System (INIS)

    Chan Heangping; Wei Jun; Zhang Yiheng; Helvie, Mark A.; Moore, Richard H.; Sahiner, Berkman; Hadjiiski, Lubomir; Kopans, Daniel B.

    2008-01-01

    The authors are developing a computer-aided detection (CAD) system for masses on digital breast tomosynthesis mammograms (DBT). Three approaches were evaluated in this study. In the first approach, mass candidate identification and feature analysis are performed in the reconstructed three-dimensional (3D) DBT volume. A mass likelihood score is estimated for each mass candidate using a linear discriminant analysis (LDA) classifier. Mass detection is determined by a decision threshold applied to the mass likelihood score. A free response receiver operating characteristic (FROC) curve that describes the detection sensitivity as a function of the number of false positives (FPs) per breast is generated by varying the decision threshold over a range. In the second approach, prescreening of mass candidate and feature analysis are first performed on the individual two-dimensional (2D) projection view (PV) images. A mass likelihood score is estimated for each mass candidate using an LDA classifier trained for the 2D features. The mass likelihood images derived from the PVs are backprojected to the breast volume to estimate the 3D spatial distribution of the mass likelihood scores. The FROC curve for mass detection can again be generated by varying the decision threshold on the 3D mass likelihood scores merged by backprojection. In the third approach, the mass likelihood scores estimated by the 3D and 2D approaches, described above, at the corresponding 3D location are combined and evaluated using FROC analysis. A data set of 100 DBT cases acquired with a GE prototype system at the Breast Imaging Laboratory in the Massachusetts General Hospital was used for comparison of the three approaches. The LDA classifiers with stepwise feature selection were designed with leave-one-case-out resampling. In FROC analysis, the CAD system for detection in the DBT volume alone achieved test sensitivities of 80% and 90% at average FP rates of 1.94 and 3.40 per breast, respectively. With the

  19. Effective Lagrangian approach to the fermion mass problem

    International Nuclear Information System (INIS)

    Shaw, D.S.; Volkas, R.R.

    1994-01-01

    An effective theory is proposed, combining the standard gauge group SU(3) C direct-product SU(2) L direct-product U(1) Y with a horizontal discrete symmetry. By assigning appropriate charges under this discrete symmetry to the various fermion fields and to (at least) two Higgs doublets, the broad spread of the fermion mass and mixing angle spectrum can be explained as a result of suppressed, non-renormalizable terms. A particular model is constructed which achieves the above while simultaneously suppressing neutral Higgs-induced flavour-changing processes. 9 refs., 3 tabs., 1 fig

  20. (S)fermion masses and lepton flavor violation. A democratic approach

    International Nuclear Information System (INIS)

    Hamaguchi, K.; Kakizaki, Mitsuru; Yamaguchi, Masahiro

    2004-01-01

    It is well-known that flavor mixing among the sfermion masses must be quite suppressed to survive various FCNC experimental bounds. One of the solutions to this supersymmetric FCNC problem is an alignment mechanism in which sfermion masses and fermion masses have some common origin and thus they are somehow aligned to each other. We propose a democratic approach to realize this idea, and illustrate how it has different predictions in slepton masses as well as lepton flavor violation from a more conventional minimal supergravity approach. This talk is based on our work in Ref. 1. (author)

  1. Mass spectrometric based approaches in urine metabolomics and biomarker discovery.

    Science.gov (United States)

    Khamis, Mona M; Adamko, Darryl J; El-Aneed, Anas

    2017-03-01

    Urine metabolomics has recently emerged as a prominent field for the discovery of non-invasive biomarkers that can detect subtle metabolic discrepancies in response to a specific disease or therapeutic intervention. Urine, compared to other biofluids, is characterized by its ease of collection, richness in metabolites and its ability to reflect imbalances of all biochemical pathways within the body. Following urine collection for metabolomic analysis, samples must be immediately frozen to quench any biogenic and/or non-biogenic chemical reactions. According to the aim of the experiment; sample preparation can vary from simple procedures such as filtration to more specific extraction protocols such as liquid-liquid extraction. Due to the lack of comprehensive studies on urine metabolome stability, higher storage temperatures (i.e. 4°C) and repetitive freeze-thaw cycles should be avoided. To date, among all analytical techniques, mass spectrometry (MS) provides the best sensitivity, selectivity and identification capabilities to analyze the majority of the metabolite composition in the urine. Combined with the qualitative and quantitative capabilities of MS, and due to the continuous improvements in its related technologies (i.e. ultra high-performance liquid chromatography [UPLC] and hydrophilic interaction liquid chromatography [HILIC]), liquid chromatography (LC)-MS is unequivocally the most utilized and the most informative analytical tool employed in urine metabolomics. Furthermore, differential isotope tagging techniques has provided a solution to ion suppression from urine matrix thus allowing for quantitative analysis. In addition to LC-MS, other MS-based technologies have been utilized in urine metabolomics. These include direct injection (infusion)-MS, capillary electrophoresis-MS and gas chromatography-MS. In this article, the current progresses of different MS-based techniques in exploring the urine metabolome as well as the recent findings in providing

  2. Probing conserved helical modules of portal complexes by mass spectrometry-based hydrogen/deuterium exchange.

    Science.gov (United States)

    Kang, Sebyung; Poliakov, Anton; Sexton, Jennifer; Renfrow, Matthew B; Prevelige, Peter E

    2008-09-05

    The Double-stranded DNA bacteriophage P22 has a ring-shaped dodecameric complex composed of the 84 kDa portal protein subunit that forms the central channel of the phage DNA packaging motor. The overall morphology of the P22 portal complex is similar to that of the portal complexes of Phi29, SPP1, T3, T7 phages and herpes simplex virus. Secondary structure prediction of P22 portal protein and its threading onto the crystal structure of the Phi29 portal complexes suggested that the P22 portal protein complex shares conserved helical modules that were found in the dodecameric interfaces of the Phi29 portal complex. To identify the amino acids involved in intersubunit contacts in the P22 portal ring complexes and validate the threading model, we performed comparative hydrogen/deuterium exchange analysis of monomeric and in vitro assembled portal proteins of P22 and the dodecameric Phi29 portal. Hydrogen/deuterium exchange experiments provided evidence of intersubunit interactions in the P22 portal complex similar to those in the Phi29 portal that map to the regions predicted to be conserved helical modules.

  3. Fractional Analysis of Escherichia coli O157:H7 by Mass Spectrometry-Based Proteomics

    Science.gov (United States)

    2012-10-01

    Bacillus subtilis . J. Bacteriol. September 2011, 193, 4821–4831; published ahead of print 8 July 2011, DOI:10.1128/JB.00223-11. 3. Kuehn, M.J... Antibiotic Resistance and Virulence”. Certain extracellular proteins of pathogenic bacteria have been shown to function in survival mechanisms such as host...The identification of molecular level components important for survival could prove useful in arenas such as vaccine and antibiotic development

  4. Mass spectrometry-based metabolomic fingerprinting for screening cold tolerance in Arabidopsis thaliana accessions

    Czech Academy of Sciences Publication Activity Database

    Václavík, L.; Mishra, Anamika; Mishra, Kumud; Hajslova, J.

    2013-01-01

    Roč. 405, č. 8 (2013), s. 2671-2683 ISSN 1618-2642 R&D Projects: GA MŠk(CZ) ED1.1.00/02.0073; GA MŠk OC08055 Institutional support: RVO:67179843 Keywords : cold tolerance * Arabidopsis thaliana * metabolomic fingerprinting * LC-MS * DART-MS * chemometric analysis Subject RIV: EH - Ecology, Behaviour Impact factor: 3.578, year: 2013

  5. N-glycosylation of colorectal cancer tissues: a liquid chromatography and mass spectrometry-based investigation.

    Science.gov (United States)

    Balog, Crina I A; Stavenhagen, Kathrin; Fung, Wesley L J; Koeleman, Carolien A; McDonnell, Liam A; Verhoeven, Aswin; Mesker, Wilma E; Tollenaar, Rob A E M; Deelder, André M; Wuhrer, Manfred

    2012-09-01

    Colorectal cancer is the third most common cancer worldwide with an annual incidence of ~1 million cases and an annual mortality rate of ~655,000 individuals. There is an urgent need for identifying novel targets to develop more sensitive, reliable, and specific tests for early stage detection of colon cancer. Post-translational modifications are known to play an important role in cancer progression and immune surveillance of tumors. In the present study, we compared the N-glycan profiles from 13 colorectal cancer tumor tissues and corresponding control colon tissues. The N-glycans were enzymatically released, purified, and labeled with 2-aminobenzoic acid. Aliquots were profiled by hydrophilic interaction liquid chromatography (HILIC-HPLC) with fluorescence detection and by negative mode MALDI-TOF-MS. Using partial least squares discriminant analysis to investigate the N-glycosylation changes in colorectal cancer, an excellent separation and prediction ability were observed for both HILIC-HPLC and MALDI-TOF-MS data. For structure elucidation, information from positive mode ESI-ion trap-MS/MS and negative mode MALDI-TOF/TOF-MS was combined. Among the features with a high separation power, structures containing a bisecting GlcNAc were found to be decreased in the tumor, whereas sulfated glycans, paucimannosidic glycans, and glycans containing a sialylated Lewis type epitope were shown to be increased in tumor tissues. In addition, core-fucosylated high mannose N-glycans were detected in tumor samples. In conclusion, the combination of HILIC and MALDI-TOF-MS profiling of N-glycans with multivariate statistical analysis demonstrated its potential for identifying N-glycosylation changes in colorectal cancer tissues and provided new leads that might be used as candidate biomarkers.

  6. Mass Spectrometry-Based Adrenal and Peripheral Venous Steroid Profiling for Subtyping Primary Aldosteronism

    NARCIS (Netherlands)

    Eisenhofer, G.; Dekkers, T.; Peitzsch, M.; Dietz, A.S.; Bidlingmaier, M.; Treitl, M.; Williams, T.A.; Bornstein, S.R.; Haase, M.; Rump, L.C.; Willenberg, H.S.; Beuschlein, F.; Deinum, J.; Lenders, J.W.; Reincke, M.

    2016-01-01

    BACKGROUND: Differentiating patients with primary aldosteronism caused by aldosterone-producing adenomas (APAs) from those with bilateral adrenal hyperplasia (BAH), which is essential for choice of therapeutic intervention, relies on adrenal venous sampling (AVS)-based measurements of aldosterone

  7. Mass Optimization of Battery/Supercapacitors Hybrid Systems Based on a Linear Programming Approach

    Science.gov (United States)

    Fleury, Benoit; Labbe, Julien

    2014-08-01

    The objective of this paper is to show that, on a specific launcher-type mission profile, a 40% gain of mass is expected using a battery/supercapacitors active hybridization instead of a single battery solution. This result is based on the use of a linear programming optimization approach to perform the mass optimization of the hybrid power supply solution.

  8. A multifunctional design approach for sustainable concrete : with application to concrete mass products

    NARCIS (Netherlands)

    Hüsken, G.

    2010-01-01

    This thesis provides a multifunctional design approach for sustainable concrete, particularly earth-moist concrete (EMC), with application to concrete mass products. EMC is a concrete with low water content and stiff consistency that is used for the production of concrete mass products, such as

  9. Deference, Denial, and Beyond: A Repertoire Approach to Mass Media and Schooling

    Science.gov (United States)

    Rymes, Betsy

    2011-01-01

    In this article, the author outlines two general research approaches, within the education world, to these mass-mediated formations: "Deference" and "Denial." Researchers who recognize the social practices that give local meaning to mass media formations and ways of speaking do not attempt to recontextualize youth media in their own social…

  10. Unfolding code for neutron spectrometry based on neural nets technology

    International Nuclear Information System (INIS)

    Ortiz R, J. M.; Vega C, H. R.

    2012-10-01

    The most delicate part of neutron spectrometry, is the unfolding process. The derivation of the spectral information is not simple because the unknown is not given directly as a result of the measurements. The drawbacks associated with traditional unfolding procedures have motivated the need of complementary approaches. Novel methods based on Artificial Neural Networks have been widely investigated. In this work, a neutron spectrum unfolding code based on neural nets technology is presented. This unfolding code called Neutron Spectrometry and Dosimetry by means of Artificial Neural Networks was designed in a graphical interface under LabVIEW programming environment. The core of the code is an embedded neural network architecture, previously optimized by the R obust Design of Artificial Neural Networks Methodology . The main features of the code are: is easy to use, friendly and intuitive to the user. This code was designed for a Bonner Sphere System based on a 6 Lil(Eu) neutron detector and a response matrix expressed in 60 energy bins taken from an International Atomic Energy Agency compilation. The main feature of the code is that as entrance data, only seven rate counts measurement with a Bonner spheres spectrometer are required for simultaneously unfold the 60 energy bins of the neutron spectrum and to calculate 15 dosimetric quantities, for radiation protection porpoises. This code generates a full report in html format with all relevant information. (Author)

  11. Unfolding code for neutron spectrometry based on neural nets technology

    Energy Technology Data Exchange (ETDEWEB)

    Ortiz R, J. M.; Vega C, H. R., E-mail: morvymm@yahoo.com.mx [Universidad Autonoma de Zacatecas, Unidad Academica de Ingenieria Electrica, Apdo. Postal 336, 98000 Zacatecas (Mexico)

    2012-10-15

    The most delicate part of neutron spectrometry, is the unfolding process. The derivation of the spectral information is not simple because the unknown is not given directly as a result of the measurements. The drawbacks associated with traditional unfolding procedures have motivated the need of complementary approaches. Novel methods based on Artificial Neural Networks have been widely investigated. In this work, a neutron spectrum unfolding code based on neural nets technology is presented. This unfolding code called Neutron Spectrometry and Dosimetry by means of Artificial Neural Networks was designed in a graphical interface under LabVIEW programming environment. The core of the code is an embedded neural network architecture, previously optimized by the {sup R}obust Design of Artificial Neural Networks Methodology{sup .} The main features of the code are: is easy to use, friendly and intuitive to the user. This code was designed for a Bonner Sphere System based on a {sup 6}Lil(Eu) neutron detector and a response matrix expressed in 60 energy bins taken from an International Atomic Energy Agency compilation. The main feature of the code is that as entrance data, only seven rate counts measurement with a Bonner spheres spectrometer are required for simultaneously unfold the 60 energy bins of the neutron spectrum and to calculate 15 dosimetric quantities, for radiation protection porpoises. This code generates a full report in html format with all relevant information. (Author)

  12. OFFGEL electrophoresis and tandem mass spectrometry approach compared with DNA-based PCR method for authentication of meat species from raw and cooked ground meat mixtures containing cattle meat, water buffalo meat and sheep meat.

    Science.gov (United States)

    Naveena, Basappa M; Jagadeesh, Deepak S; Jagadeesh Babu, A; Madhava Rao, T; Kamuni, Veeranna; Vaithiyanathan, S; Kulkarni, Vinayak V; Rapole, Srikanth

    2017-10-15

    The present study compared the accuracy of an OFFGEL electrophoresis and tandem mass spectrometry-based proteomic approach with a DNA-based method for meat species identification from raw and cooked ground meat mixes containing cattle, water buffalo and sheep meat. The proteomic approach involved the separation of myofibrillar proteins using OFFGEL electrophoresis, SDS-PAGE and protein identification by MALDI-TOF MS. Species-specific peptides derived from myosin light chain-1 and 2 were identified for authenticating buffalo meat spiked at a minimum 0.5% level in sheep meat with high confidence. Relative quantification of buffalo meat mixed with sheep meat was done by quantitative label-free mass spectrometry using UPLC-QTOF and PLGS search engine to substantiate the confidence level of the data. In the DNA-based method, PCR amplification of mitochondrial D loop gene using species specific primers found 226bp and 126bp product amplicons for buffalo and cattle meat, respectively. The method was efficient in detecting a minimum of 0.5% and 1.0% when buffalo meat was spiked with cattle meat in raw and cooked meat mixes. Copyright © 2017 Elsevier Ltd. All rights reserved.

  13. Mass

    International Nuclear Information System (INIS)

    Quigg, Chris

    2007-01-01

    In the classical physics we inherited from Isaac Newton, mass does not arise, it simply is. The mass of a classical object is the sum of the masses of its parts. Albert Einstein showed that the mass of a body is a measure of its energy content, inviting us to consider the origins of mass. The protons we accelerate at Fermilab are prime examples of Einsteinian matter: nearly all of their mass arises from stored energy. Missing mass led to the discovery of the noble gases, and a new form of missing mass leads us to the notion of dark matter. Starting with a brief guided tour of the meanings of mass, the colloquium will explore the multiple origins of mass. We will see how far we have come toward understanding mass, and survey the issues that guide our research today.

  14. Heat and mass transfer intensification and shape optimization a multi-scale approach

    CERN Document Server

    2013-01-01

    Is the heat and mass transfer intensification defined as a new paradigm of process engineering, or is it just a common and old idea, renamed and given the current taste? Where might intensification occur? How to achieve intensification? How the shape optimization of thermal and fluidic devices leads to intensified heat and mass transfers? To answer these questions, Heat & Mass Transfer Intensification and Shape Optimization: A Multi-scale Approach clarifies  the definition of the intensification by highlighting the potential role of the multi-scale structures, the specific interfacial area, the distribution of driving force, the modes of energy supply and the temporal aspects of processes.   A reflection on the methods of process intensification or heat and mass transfer enhancement in multi-scale structures is provided, including porous media, heat exchangers, fluid distributors, mixers and reactors. A multi-scale approach to achieve intensification and shape optimization is developed and clearly expla...

  15. GIS-based Approaches to Catchment Area Analyses of Mass Transit

    DEFF Research Database (Denmark)

    Andersen, Jonas Lohmann Elkjær; Landex, Alex

    2009-01-01

    Catchment area analyses of stops or stations are used to investigate potential number of travelers to public transportation. These analyses are considered a strong decision tool in the planning process of mass transit especially railroads. Catchment area analyses are GIS-based buffer and overlay...... analyses with different approaches depending on the desired level of detail. A simple but straightforward approach to implement is the Circular Buffer Approach where catchment areas are circular. A more detailed approach is the Service Area Approach where catchment areas are determined by a street network...... search to simulate the actual walking distances. A refinement of the Service Area Approach is to implement additional time resistance in the network search to simulate obstacles in the walking environment. This paper reviews and compares the different GIS-based catchment area approaches, their level...

  16. Lattice Hamiltonian approach to the massless Schwinger model. Precise extraction of the mass gap

    International Nuclear Information System (INIS)

    Cichy, Krzysztof; Poznan Univ.; Kujawa-Cichy, Agnieszka; Szyniszewski, Marcin; Manchester Univ.

    2012-12-01

    We present results of applying the Hamiltonian approach to the massless Schwinger model. A finite basis is constructed using the strong coupling expansion to a very high order. Using exact diagonalization, the continuum limit can be reliably approached. This allows to reproduce the analytical results for the ground state energy, as well as the vector and scalar mass gaps to an outstanding precision better than 10 -6 %.

  17. Lattice Hamiltonian approach to the massless Schwinger model. Precise extraction of the mass gap

    Energy Technology Data Exchange (ETDEWEB)

    Cichy, Krzysztof [Deutsches Elektronen-Synchrotron (DESY), Zeuthen (Germany). John von Neumann-Inst. fuer Computing NIC; Poznan Univ. (Poland). Faculty of Physics; Kujawa-Cichy, Agnieszka [Poznan Univ. (Poland). Faculty of Physics; Szyniszewski, Marcin [Poznan Univ. (Poland). Faculty of Physics; Manchester Univ. (United Kingdom). NOWNano DTC

    2012-12-15

    We present results of applying the Hamiltonian approach to the massless Schwinger model. A finite basis is constructed using the strong coupling expansion to a very high order. Using exact diagonalization, the continuum limit can be reliably approached. This allows to reproduce the analytical results for the ground state energy, as well as the vector and scalar mass gaps to an outstanding precision better than 10{sup -6} %.

  18. Sliding Mode Control for Mass Moment Aerospace Vehicles Using Dynamic Inversion Approach

    Directory of Open Access Journals (Sweden)

    Xiao-Yu Zhang

    2013-01-01

    Full Text Available The moving mass actuation technique offers significant advantages over conventional aerodynamic control surfaces and reaction control systems, because the actuators are contained entirely within the airframe geometrical envelope. Modeling, control, and simulation of Mass Moment Aerospace Vehicles (MMAV utilizing moving mass actuators are discussed. Dynamics of the MMAV are separated into two parts on the basis of the two time-scale separation theory: the dynamics of fast state and the dynamics of slow state. And then, in order to restrain the system chattering and keep the track performance of the system by considering aerodynamic parameter perturbation, the flight control system is designed for the two subsystems, respectively, utilizing fuzzy sliding mode control approach. The simulation results describe the effectiveness of the proposed autopilot design approach. Meanwhile, the chattering phenomenon that frequently appears in the conventional variable structure systems is also eliminated without deteriorating the system robustness.

  19. Refining mass formulas for astrophysical applications: A Bayesian neural network approach

    Science.gov (United States)

    Utama, R.; Piekarewicz, J.

    2017-10-01

    Background: Exotic nuclei, particularly those near the drip lines, are at the core of one of the fundamental questions driving nuclear structure and astrophysics today: What are the limits of nuclear binding? Exotic nuclei play a critical role in both informing theoretical models as well as in our understanding of the origin of the heavy elements. Purpose: Our aim is to refine existing mass models through the training of an artificial neural network that will mitigate the large model discrepancies far away from stability. Methods: The basic paradigm of our two-pronged approach is an existing mass model that captures as much as possible of the underlying physics followed by the implementation of a Bayesian neural network (BNN) refinement to account for the missing physics. Bayesian inference is employed to determine the parameters of the neural network so that model predictions may be accompanied by theoretical uncertainties. Results: Despite the undeniable quality of the mass models adopted in this work, we observe a significant improvement (of about 40%) after the BNN refinement is implemented. Indeed, in the specific case of the Duflo-Zuker mass formula, we find that the rms deviation relative to experiment is reduced from σrms=0.503 MeV to σrms=0.286 MeV. These newly refined mass tables are used to map the neutron drip lines (or rather "drip bands") and to study a few critical r -process nuclei. Conclusions: The BNN approach is highly successful in refining the predictions of existing mass models. In particular, the large discrepancy displayed by the original "bare" models in regions where experimental data are unavailable is considerably quenched after the BNN refinement. This lends credence to our approach and has motivated us to publish refined mass tables that we trust will be helpful for future astrophysical applications.

  20. The development of an efficient mass balance approach for the purity assignment of organic calibration standards.

    Science.gov (United States)

    Davies, Stephen R; Alamgir, Mahiuddin; Chan, Benjamin K H; Dang, Thao; Jones, Kai; Krishnaswami, Maya; Luo, Yawen; Mitchell, Peter S R; Moawad, Michael; Swan, Hilton; Tarrant, Greg J

    2015-10-01

    The purity determination of organic calibration standards using the traditional mass balance approach is described. Demonstrated examples highlight the potential for bias in each measurement and the need to implement an approach that provides a cross-check for each result, affording fit for purpose purity values in a timely and cost-effective manner. Chromatographic techniques such as gas chromatography with flame ionisation detection (GC-FID) and high-performance liquid chromatography with UV detection (HPLC-UV), combined with mass and NMR spectroscopy, provide a detailed impurity profile allowing an efficient conversion of chromatographic peak areas into relative mass fractions, generally avoiding the need to calibrate each impurity present. For samples analysed by GC-FID, a conservative measurement uncertainty budget is described, including a component to cover potential variations in the response of each unidentified impurity. An alternative approach is also detailed in which extensive purification eliminates the detector response factor issue, facilitating the certification of a super-pure calibration standard which can be used to quantify the main component in less-pure candidate materials. This latter approach is particularly useful when applying HPLC analysis with UV detection. Key to the success of this approach is the application of both qualitative and quantitative (1)H NMR spectroscopy.

  1. Different top-down approaches to estimate measurement uncertainty of whole blood tacrolimus mass concentration values.

    Science.gov (United States)

    Rigo-Bonnin, Raül; Blanco-Font, Aurora; Canalias, Francesca

    2018-05-08

    Values of mass concentration of tacrolimus in whole blood are commonly used by the clinicians for monitoring the status of a transplant patient and for checking whether the administered dose of tacrolimus is effective. So, clinical laboratories must provide results as accurately as possible. Measurement uncertainty can allow ensuring reliability of these results. The aim of this study was to estimate measurement uncertainty of whole blood mass concentration tacrolimus values obtained by UHPLC-MS/MS using two top-down approaches: the single laboratory validation approach and the proficiency testing approach. For the single laboratory validation approach, we estimated the uncertainties associated to the intermediate imprecision (using long-term internal quality control data) and the bias (utilizing a certified reference material). Next, we combined them together with the uncertainties related to the calibrators-assigned values to obtain a combined uncertainty for, finally, to calculate the expanded uncertainty. For the proficiency testing approach, the uncertainty was estimated in a similar way that the single laboratory validation approach but considering data from internal and external quality control schemes to estimate the uncertainty related to the bias. The estimated expanded uncertainty for single laboratory validation, proficiency testing using internal and external quality control schemes were 11.8%, 13.2%, and 13.0%, respectively. After performing the two top-down approaches, we observed that their uncertainty results were quite similar. This fact would confirm that either two approaches could be used to estimate the measurement uncertainty of whole blood mass concentration tacrolimus values in clinical laboratories. Copyright © 2018 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

  2. Evaluation of a mass-balance approach to determine consumptive water use in northeastern Illinois

    Science.gov (United States)

    Mills, Patrick C.; Duncker, James J.; Over, Thomas M.; Marian Domanski,; ,; Engel, Frank

    2014-01-01

    A principal component of evaluating and managing water use is consumptive use. This is the portion of water withdrawn for a particular use, such as residential, which is evaporated, transpired, incorporated into products or crops, consumed by humans or livestock, or otherwise removed from the immediate water environment. The amount of consumptive use may be estimated by a water (mass)-balance approach; however, because of the difficulty of obtaining necessary data, its application typically is restricted to the facility scale. The general governing mass-balance equation is: Consumptive use = Water supplied - Return flows.

  3. A Clifford algebra approach to chiral symmetry breaking and fermion mass hierarchies

    Science.gov (United States)

    Lu, Wei

    2017-09-01

    We propose a Clifford algebra approach to chiral symmetry breaking and fermion mass hierarchies in the context of composite Higgs bosons. Standard model fermions are represented by algebraic spinors of six-dimensional binary Clifford algebra, while ternary Clifford algebra-related flavor projection operators control allowable flavor-mixing interactions. There are three composite electroweak Higgs bosons resulted from top quark, tau neutrino, and tau lepton condensations. Each of the three condensations gives rise to masses of four different fermions. The fermion mass hierarchies within these three groups are determined by four-fermion condensations, which break two global chiral symmetries. The four-fermion condensations induce axion-like pseudo-Nambu-Goldstone bosons and can be dark matter candidates. In addition to the 125 GeV Higgs boson observed at the Large Hadron Collider, we anticipate detection of tau neutrino composite Higgs boson via the charm quark decay channel.

  4. A data base approach for prediction of deforestation-induced mass wasting events

    Science.gov (United States)

    Logan, T. L.

    1981-01-01

    A major topic of concern in timber management is determining the impact of clear-cutting on slope stability. Deforestation treatments on steep mountain slopes have often resulted in a high frequency of major mass wasting events. The Geographic Information System (GIS) is a potentially useful tool for predicting the location of mass wasting sites. With a raster-based GIS, digitally encoded maps of slide hazard parameters can be overlayed and modeled to produce new maps depicting high probability slide areas. The present investigation has the objective to examine the raster-based information system as a tool for predicting the location of the clear-cut mountain slopes which are most likely to experience shallow soil debris avalanches. A literature overview is conducted, taking into account vegetation, roads, precipitation, soil type, slope-angle and aspect, and models predicting mass soil movements. Attention is given to a data base approach and aspects of slide prediction.

  5. A new approach for accurate mass assignment on a multi-turn time-of-flight mass spectrometer.

    Science.gov (United States)

    Hondo, Toshinobu; Jensen, Kirk R; Aoki, Jun; Toyoda, Michisato

    2017-12-01

    A simple, effective accurate mass assignment procedure for a time-of-flight mass spectrometer is desirable. External mass calibration using a mass calibration standard together with an internal mass reference (lock mass) is a common technique for mass assignment, however, using polynomial fitting can result in mass-dependent errors. By using the multi-turn time-of-flight mass spectrometer infiTOF-UHV, we were able to obtain multiple time-of-flight data from an ion monitored under several different numbers of laps that was then used to calculate a mass calibration equation. We have developed a data acquisition system that simultaneously monitors spectra at several different lap conditions with on-the-fly centroid determination and scan law estimation, which is a function of acceleration voltage, flight path, and instrumental time delay. Less than 0.9 mDa mass errors were observed for assigned mass to charge ratios ( m/z) ranging between 4 and 134 using only 40 Ar + as a reference. It was also observed that estimating the scan law on-the-fly provides excellent mass drift compensation.

  6. A Bayesian geostatistical approach for evaluating the uncertainty of contaminant mass discharges from point sources

    Science.gov (United States)

    Troldborg, M.; Nowak, W.; Binning, P. J.; Bjerg, P. L.

    2012-12-01

    Estimates of mass discharge (mass/time) are increasingly being used when assessing risks of groundwater contamination and designing remedial systems at contaminated sites. Mass discharge estimates are, however, prone to rather large uncertainties as they integrate uncertain spatial distributions of both concentration and groundwater flow velocities. For risk assessments or any other decisions that are being based on mass discharge estimates, it is essential to address these uncertainties. We present a novel Bayesian geostatistical approach for quantifying the uncertainty of the mass discharge across a multilevel control plane. The method decouples the flow and transport simulation and has the advantage of avoiding the heavy computational burden of three-dimensional numerical flow and transport simulation coupled with geostatistical inversion. It may therefore be of practical relevance to practitioners compared to existing methods that are either too simple or computationally demanding. The method is based on conditional geostatistical simulation and accounts for i) heterogeneity of both the flow field and the concentration distribution through Bayesian geostatistics (including the uncertainty in covariance functions), ii) measurement uncertainty, and iii) uncertain source zone geometry and transport parameters. The method generates multiple equally likely realizations of the spatial flow and concentration distribution, which all honour the measured data at the control plane. The flow realizations are generated by analytical co-simulation of the hydraulic conductivity and the hydraulic gradient across the control plane. These realizations are made consistent with measurements of both hydraulic conductivity and head at the site. An analytical macro-dispersive transport solution is employed to simulate the mean concentration distribution across the control plane, and a geostatistical model of the Box-Cox transformed concentration data is used to simulate observed

  7. A novel featureless approach to mass detection in digital mammograms based on support vector machines

    Energy Technology Data Exchange (ETDEWEB)

    Campanini, Renato [Department of Physics, University of Bologna, and INFN, Bologna (Italy); Dongiovanni, Danilo [Department of Physics, University of Bologna, and INFN, Bologna (Italy); Iampieri, Emiro [Department of Physics, University of Bologna, and INFN, Bologna (Italy); Lanconelli, Nico [Department of Physics, University of Bologna, and INFN, Bologna (Italy); Masotti, Matteo [Department of Physics, University of Bologna, and INFN, Bologna (Italy); Palermo, Giuseppe [Department of Physics, University of Bologna, and INFN, Bologna (Italy); Riccardi, Alessandro [Department of Physics, University of Bologna, and INFN, Bologna (Italy); Roffilli, Matteo [Department of Computer Science, University of Bologna, Bologna (Italy)

    2004-03-21

    In this work, we present a novel approach to mass detection in digital mammograms. The great variability of the appearance of masses is the main obstacle to building a mass detection method. It is indeed demanding to characterize all the varieties of masses with a reduced set of features. Hence, in our approach we have chosen not to extract any feature, for the detection of the region of interest; in contrast, we exploit all the information available on the image. A multiresolution overcomplete wavelet representation is performed, in order to codify the image with redundancy of information. The vectors of the very-large space obtained are then provided to a first support vector machine (SVM) classifier. The detection task is considered here as a two-class pattern recognition problem: crops are classified as suspect or not, by using this SVM classifier. False candidates are eliminated with a second cascaded SVM. To further reduce the number of false positives, an ensemble of experts is applied: the final suspect regions are achieved by using a voting strategy. The sensitivity of the presented system is nearly 80% with a false-positive rate of 1.1 marks per image, estimated on images coming from the USF DDSM database.

  8. A Real-Time Temperature Data Transmission Approach for Intelligent Cooling Control of Mass Concrete

    Directory of Open Access Journals (Sweden)

    Peng Lin

    2014-01-01

    Full Text Available The primary aim of the study presented in this paper is to propose a real-time temperature data transmission approach for intelligent cooling control of mass concrete. A mathematical description of a digital temperature control model is introduced in detail. Based on pipe mounted and electrically linked temperature sensors, together with postdata handling hardware and software, a stable, real-time, highly effective temperature data transmission solution technique is developed and utilized within the intelligent mass concrete cooling control system. Once the user has issued the relevant command, the proposed programmable logic controllers (PLC code performs all necessary steps without further interaction. The code can control the hardware, obtain, read, and perform calculations, and display the data accurately. Hardening concrete is an aggregate of complex physicochemical processes including the liberation of heat. The proposed control system prevented unwanted structural change within the massive concrete blocks caused by these exothermic processes based on an application case study analysis. In conclusion, the proposed temperature data transmission approach has proved very useful for the temperature monitoring of a high arch dam and is able to control thermal stresses in mass concrete for similar projects involving mass concrete.

  9. How mass spectrometric approaches applied to bacterial identification have revolutionized the study of human gut microbiota.

    Science.gov (United States)

    Grégory, Dubourg; Chaudet, Hervé; Lagier, Jean-Christophe; Raoult, Didier

    2018-03-01

    Describing the human hut gut microbiota is one the most exciting challenges of the 21 st century. Currently, high-throughput sequencing methods are considered as the gold standard for this purpose, however, they suffer from several drawbacks, including their inability to detect minority populations. The advent of mass-spectrometric (MS) approaches to identify cultured bacteria in clinical microbiology enabled the creation of the culturomics approach, which aims to establish a comprehensive repertoire of cultured prokaryotes from human specimens using extensive culture conditions. Areas covered: This review first underlines how mass spectrometric approaches have revolutionized clinical microbiology. It then highlights the contribution of MS-based methods to culturomics studies, paying particular attention to the extension of the human gut microbiota repertoire through the discovery of new bacterial species. Expert commentary: MS-based approaches have enabled cultivation methods to be resuscitated to study the human gut microbiota and thus to fill in the blanks left by high-throughput sequencing methods in terms of culturing minority populations. Continued efforts to recover new taxa using culture methods, combined with their rapid implementation in genomic databases, would allow for an exhaustive analysis of the gut microbiota through the use of a comprehensive approach.

  10. A survey of existing and proposed classical and quantum approaches to the photon mass

    Science.gov (United States)

    Spavieri, G.; Quintero, J.; Gillies, G. T.; Rodríguez, M.

    2011-02-01

    Over the past twenty years, there have been several careful experimental, observational and phenomenological investigations aimed at searching for and establishing ever tighter bounds on the possible mass of the photon. There are many fascinating and paradoxical physical implications that would arise from the presence of even a very small value for it, and thus such searches have always been well motivated in terms of the new physics that would result. We provide a brief overview of the theoretical background and classical motivations for this work and the early tests of the exactness of Coulomb's law that underlie it. We then go on to address the modern situation, in which quantum physics approaches come to attention. Among them we focus especially on the implications that the Aharonov-Bohm and Aharonov-Casher class of effects have on searches for a photon mass. These arise in several different ways and can lead to experiments that might involve the interaction of magnetic dipoles, electric dipoles, or charged particles with suitable potentials. Still other quantum-based approaches employ measurements of the g-factor of the electron. Plausible target sensitivities for limits on the photon mass as sought by the various quantum approaches are in the range of 10-53 to 10-54 g. Possible experimental arrangements for the associated experiments are discussed. We close with an assessment of the state of the art and a prognosis for future work.

  11. A survey of existing and proposed classical and quantum approaches to the photon mass

    International Nuclear Information System (INIS)

    Spavieri, G.; Quintero, J.; Gillies, G.T.; Rodriguez, M.

    2011-01-01

    Over the past twenty years, there have been several careful experimental, observational and phenomenological investigations aimed at searching for and establishing ever tighter bounds on the possible mass of the photon. There are many fascinating and paradoxical physical implications that would arise from the presence of even a very small value for it, and thus such searches have always been well motivated in terms of the new physics that would result. We provide a brief overview of the theoretical background and classical motivations for this work and the early tests of the exactness of Coulomb's law that underlie it. We then go on to address the modern situation, in which quantum physics approaches come to attention. Among them we focus especially on the implications that the Aharonov-Bohm and Aharonov-Casher class of effects have on searches for a photon mass. These arise in several different ways and can lead to experiments that might involve the interaction of magnetic dipoles, electric dipoles, or charged particles with suitable potentials. Still other quantum-based approaches employ measurements of the g-factor of the electron. Plausible target sensitivities for limits on the photon mass as sought by the various quantum approaches are in the range of 10 -53 to 10 -54 g. Possible experimental arrangements for the associated experiments are discussed. We close with an assessment of the state of the art and a prognosis for future work. (authors)

  12. An enhanced nonlinear damping approach accounting for system constraints in active mass dampers

    Science.gov (United States)

    Venanzi, Ilaria; Ierimonti, Laura; Ubertini, Filippo

    2015-11-01

    Active mass dampers are a viable solution for mitigating wind-induced vibrations in high-rise buildings and improve occupants' comfort. Such devices suffer particularly when they reach force saturation of the actuators and maximum extension of their stroke, which may occur in case of severe loading conditions (e.g. wind gust and earthquake). Exceeding actuators' physical limits can impair the control performance of the system or even lead to devices damage, with consequent need for repair or substitution of part of the control system. Controllers for active mass dampers should account for their technological limits. Prior work of the authors was devoted to stroke issues and led to the definition of a nonlinear damping approach, very easy to implement in practice. It consisted of a modified skyhook algorithm complemented with a nonlinear braking force to reverse the direction of the mass before reaching the stroke limit. This paper presents an enhanced version of this approach, also accounting for force saturation of the actuator and keeping the simplicity of implementation. This is achieved by modulating the control force by a nonlinear smooth function depending on the ratio between actuator's force and saturation limit. Results of a numerical investigation show that the proposed approach provides similar results to the method of the State Dependent Riccati Equation, a well-established technique for designing optimal controllers for constrained systems, yet very difficult to apply in practice.

  13. Mass Media as Actor in Political Process: Evolution of the Western Approaches since the 1950s. (Part 1)

    OpenAIRE

    Гуторов, Владимир Александрович

    2013-01-01

    The author analyses evolution of western political science’s approaches to mass media and mass media’s role in political process in liberal democracies. The author focuses on theories of “Minimal Effect,” “Mediocracy,” “Effects Research,” “Tеxt Analysis,” “Use and Gratification Approach.” The author discusses A. Giddens’s structuration theory as the most elaborate approach to interpreting the role of mass media in the western political and social science.Key words: mass and political communic...

  14. Recent advances in applying mass spectrometry and systems biology to determine brain dynamics.

    Science.gov (United States)

    Scifo, Enzo; Calza, Giulio; Fuhrmann, Martin; Soliymani, Rabah; Baumann, Marc; Lalowski, Maciej

    2017-06-01

    Neurological disorders encompass various pathologies which disrupt normal brain physiology and function. Poor understanding of their underlying molecular mechanisms and their societal burden argues for the necessity of novel prevention strategies, early diagnostic techniques and alternative treatment options to reduce the scale of their expected increase. Areas covered: This review scrutinizes mass spectrometry based approaches used to investigate brain dynamics in various conditions, including neurodegenerative and neuropsychiatric disorders. Different proteomics workflows for isolation/enrichment of specific cell populations or brain regions, sample processing; mass spectrometry technologies, for differential proteome quantitation, analysis of post-translational modifications and imaging approaches in the brain are critically deliberated. Future directions, including analysis of cellular sub-compartments, targeted MS platforms (selected/parallel reaction monitoring) and use of mass cytometry are also discussed. Expert commentary: Here, we summarize and evaluate current mass spectrometry based approaches for determining brain dynamics in health and diseases states, with a focus on neurological disorders. Furthermore, we provide insight on current trends and new MS technologies with potential to improve this analysis.

  15. Mass Spectrometry Imaging of Biological Tissue: An Approach for Multicenter Studies

    Energy Technology Data Exchange (ETDEWEB)

    Rompp, Andreas; Both, Jean-Pierre; Brunelle, Alain; Heeren, Ronald M.; Laprevote, Olivier; Prideaux, Brendan; Seyer, Alexandre; Spengler, Bernhard; Stoeckli, Markus; Smith, Donald F.

    2015-03-01

    Mass spectrometry imaging has become a popular tool for probing the chemical complexity of biological surfaces. This led to the development of a wide range of instrumentation and preparation protocols. It is thus desirable to evaluate and compare the data output from different methodologies and mass spectrometers. Here, we present an approach for the comparison of mass spectrometry imaging data from different laboratories (often referred to as multicenter studies). This is exemplified by the analysis of mouse brain sections in five laboratories in Europe and the USA. The instrumentation includes matrix-assisted laser desorption/ionization (MALDI)-time-of-flight (TOF), MALDI-QTOF, MALDIFourier transform ion cyclotron resonance (FTICR), atmospheric-pressure (AP)-MALDI-Orbitrap, and cluster TOF-secondary ion mass spectrometry (SIMS). Experimental parameters such as measurement speed, imaging bin width, and mass spectrometric parameters are discussed. All datasets were converted to the standard data format imzML and displayed in a common open-source software with identical parameters for visualization, which facilitates direct comparison of MS images. The imzML conversion also allowed exchange of fully functional MS imaging datasets between the different laboratories. The experiments ranged from overview measurements of the full mouse brain to detailed analysis of smaller features (depending on spatial resolution settings), but common histological features such as the corpus callosum were visible in all measurements. High spatial resolution measurements of AP-MALDI-Orbitrap and TOF-SIMS showed comparable structures in the low-micrometer range. We discuss general considerations for planning and performing multicenter studies in mass spectrometry imaging. This includes details on the selection, distribution, and preparation of tissue samples as well as on data handling. Such multicenter studies in combination with ongoing activities for reporting guidelines, a common

  16. Superconductivity. Quasiparticle mass enhancement approaching optimal doping in a high-T(c) superconductor.

    Science.gov (United States)

    Ramshaw, B J; Sebastian, S E; McDonald, R D; Day, James; Tan, B S; Zhu, Z; Betts, J B; Liang, Ruixing; Bonn, D A; Hardy, W N; Harrison, N

    2015-04-17

    In the quest for superconductors with higher transition temperatures (T(c)), one emerging motif is that electronic interactions favorable for superconductivity can be enhanced by fluctuations of a broken-symmetry phase. Recent experiments have suggested the existence of the requisite broken-symmetry phase in the high-T(c) cuprates, but the impact of such a phase on the ground-state electronic interactions has remained unclear. We used magnetic fields exceeding 90 tesla to access the underlying metallic state of the cuprate YBa2Cu3O(6+δ) over a wide range of doping, and observed magnetic quantum oscillations that reveal a strong enhancement of the quasiparticle effective mass toward optimal doping. This mass enhancement results from increasing electronic interactions approaching optimal doping, and suggests a quantum critical point at a hole doping of p(crit) ≈ 0.18. Copyright © 2015, American Association for the Advancement of Science.

  17. A Ligand-observed Mass Spectrometry Approach Integrated into the Fragment Based Lead Discovery Pipeline

    Science.gov (United States)

    Chen, Xin; Qin, Shanshan; Chen, Shuai; Li, Jinlong; Li, Lixin; Wang, Zhongling; Wang, Quan; Lin, Jianping; Yang, Cheng; Shui, Wenqing

    2015-01-01

    In fragment-based lead discovery (FBLD), a cascade combining multiple orthogonal technologies is required for reliable detection and characterization of fragment binding to the target. Given the limitations of the mainstream screening techniques, we presented a ligand-observed mass spectrometry approach to expand the toolkits and increase the flexibility of building a FBLD pipeline especially for tough targets. In this study, this approach was integrated into a FBLD program targeting the HCV RNA polymerase NS5B. Our ligand-observed mass spectrometry analysis resulted in the discovery of 10 hits from a 384-member fragment library through two independent screens of complex cocktails and a follow-up validation assay. Moreover, this MS-based approach enabled quantitative measurement of weak binding affinities of fragments which was in general consistent with SPR analysis. Five out of the ten hits were then successfully translated to X-ray structures of fragment-bound complexes to lay a foundation for structure-based inhibitor design. With distinctive strengths in terms of high capacity and speed, minimal method development, easy sample preparation, low material consumption and quantitative capability, this MS-based assay is anticipated to be a valuable addition to the repertoire of current fragment screening techniques. PMID:25666181

  18. Risk-oriented approach application at planning and orginizing antiepidemic provision of mass events

    Directory of Open Access Journals (Sweden)

    D.V. Efremenko

    2017-03-01

    Full Text Available Mass events tend to become more and more dangerous for population health, as they cause various health risks, including infectious pathologies risks. Our research goal was to work out scientifically grounded approaches to assessing and managing epidemiologic risks as well as analyze their application practices implemented during preparation to the Olympics-2014, the Games themselves, as well as other mass events which took place in 2014–2016. We assessed epidemiologic complications risks with the use of diagnostic test-systems and applying a new technique which allowed for mass events peculiarities. The technique is based on infections ranking as per 3 potential danger categories in accordance with created criteria which represented quantitative and qualitative predictive parameters (predictors. Application of risk-oriented approach and multi-factor analysis allowed us to detect exact possible maximum requirements for providing sanitary-epidemiologic welfare in terms of each separate nosologic form. As we enhanced our laboratory base with test-systems to provide specific indication as per accomplished calculations, it enabled us, on one hand, to secure the required preparations, and, on the other hand, to avoid unnecessary expenditures. To facilitate decision-making process during the Olympics-2014 we used an innovative product, namely, a computer program based on geoinformation system (GIS. It helped us to simplify and to accelerate information exchange within the frameworks of intra- and interdepartmental interaction. "Dynamic epidemiologic threshold" was daily calculated for measles, chickenpox, acute enteric infections and acute respiratory viral infections of various etiology. And if it was exceeded or possibility of "epidemiologic spot" for one or several nosologies occurred, an automatic warning appeared in GIS. Planning prevention activities regarding feral herd infections and zoogenous extremely dangerous infections which were endemic

  19. A Bayesian geostatistical approach for evaluating the uncertainty of contaminant mass discharges from point sources

    DEFF Research Database (Denmark)

    Troldborg, Mads; Nowak, Wolfgang; Binning, Philip John

    and the hydraulic gradient across the control plane and are consistent with measurements of both hydraulic conductivity and head at the site. An analytical macro-dispersive transport solution is employed to simulate the mean concentration distribution across the control plane, and a geostatistical model of the Box-Cox...... transformed concentration data is used to simulate observed deviations from this mean solution. By combining the flow and concentration realizations, a mass discharge probability distribution is obtained. Tests show that the decoupled approach is both efficient and able to provide accurate uncertainty...

  20. In silico approaches to study mass and energy flows in microbial consortia: a syntrophic case study

    Directory of Open Access Journals (Sweden)

    Mallette Natasha

    2009-12-01

    Full Text Available Abstract Background Three methods were developed for the application of stoichiometry-based network analysis approaches including elementary mode analysis to the study of mass and energy flows in microbial communities. Each has distinct advantages and disadvantages suitable for analyzing systems with different degrees of complexity and a priori knowledge. These approaches were tested and compared using data from the thermophilic, phototrophic mat communities from Octopus and Mushroom Springs in Yellowstone National Park (USA. The models were based on three distinct microbial guilds: oxygenic phototrophs, filamentous anoxygenic phototrophs, and sulfate-reducing bacteria. Two phases, day and night, were modeled to account for differences in the sources of mass and energy and the routes available for their exchange. Results The in silico models were used to explore fundamental questions in ecology including the prediction of and explanation for measured relative abundances of primary producers in the mat, theoretical tradeoffs between overall productivity and the generation of toxic by-products, and the relative robustness of various guild interactions. Conclusion The three modeling approaches represent a flexible toolbox for creating cellular metabolic networks to study microbial communities on scales ranging from cells to ecosystems. A comparison of the three methods highlights considerations for selecting the one most appropriate for a given microbial system. For instance, communities represented only by metagenomic data can be modeled using the pooled method which analyzes a community's total metabolic potential without attempting to partition enzymes to different organisms. Systems with extensive a priori information on microbial guilds can be represented using the compartmentalized technique, employing distinct control volumes to separate guild-appropriate enzymes and metabolites. If the complexity of a compartmentalized network creates an

  1. Complexified quantum field theory and 'mass without mass' from multidimensional fractional actionlike variational approach with dynamical fractional exponents

    International Nuclear Information System (INIS)

    El-Nabulsi, Ahmad Rami

    2009-01-01

    Multidimensional fractional actionlike variational problem with time-dependent dynamical fractional exponents is constructed. Fractional Euler-Lagrange equations are derived and discussed in some details. The results obtained are used to explore some novel aspects of fractional quantum field theory where many interesting consequences are revealed, in particular the complexification of quantum field theory, in particular Dirac operators and the novel notion of 'mass without mass'.

  2. A mass graph-based approach for the identification of modified proteoforms using top-down tandem mass spectra.

    Science.gov (United States)

    Kou, Qiang; Wu, Si; Tolic, Nikola; Paša-Tolic, Ljiljana; Liu, Yunlong; Liu, Xiaowen

    2017-05-01

    Although proteomics has rapidly developed in the past decade, researchers are still in the early stage of exploring the world of complex proteoforms, which are protein products with various primary structure alterations resulting from gene mutations, alternative splicing, post-translational modifications, and other biological processes. Proteoform identification is essential to mapping proteoforms to their biological functions as well as discovering novel proteoforms and new protein functions. Top-down mass spectrometry is the method of choice for identifying complex proteoforms because it provides a 'bird's eye view' of intact proteoforms. The combinatorial explosion of various alterations on a protein may result in billions of possible proteoforms, making proteoform identification a challenging computational problem. We propose a new data structure, called the mass graph, for efficient representation of proteoforms and design mass graph alignment algorithms. We developed TopMG, a mass graph-based software tool for proteoform identification by top-down mass spectrometry. Experiments on top-down mass spectrometry datasets showed that TopMG outperformed existing methods in identifying complex proteoforms. http://proteomics.informatics.iupui.edu/software/topmg/. xwliu@iupui.edu. Supplementary data are available at Bioinformatics online. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com

  3. Doping control analysis of trimetazidine and characterization of major metabolites using mass spectrometric approaches.

    Science.gov (United States)

    Sigmund, Gerd; Koch, Anja; Orlovius, Anne-Katrin; Guddat, Sven; Thomas, Andreas; Schänzer, Wilhelm; Thevis, Mario

    2014-01-01

    Since January 2014, the anti-anginal drug trimetazidine [1-(2,3,4-trimethoxybenzyl)-piperazine] has been classified as prohibited substance by the World Anti-Doping Agency (WADA), necessitating specific and robust detection methods in sports drug testing laboratories. In the present study, the implementation of the intact therapeutic agent into two different initial testing procedures based on gas chromatography-mass spectrometry (GC-MS) and liquid chromatography-tandem mass spectrometry (LC-MS/MS) is reported, along with the characterization of urinary metabolites by electrospray ionization-high resolution/high accuracy (tandem) mass spectrometry. For GC-MS analyses, urine samples were subjected to liquid-liquid extraction sample preparation, while LC-MS/MS analyses were conducted by established 'dilute-and-inject' approaches. Both screening methods were validated for trimetazidine concerning specificity, limits of detection (0.5-50 ng/mL), intra-day and inter-day imprecision (doping control samples were used to complement the LC-MS/MS-based assay, although intact trimetazidine was found at highest abundance of the relevant trimetazidine-related analytes in all tested sports drug testing samples. Retrospective data mining regarding doping control analyses conducted between 1999 and 2013 at the Cologne Doping Control Laboratory concerning trimetazidine revealed a considerable prevalence of the drug particularly in endurance and strength sports accounting for up to 39 findings per year. Copyright © 2014 John Wiley & Sons, Ltd.

  4. Coupled sulfur isotopic and chemical mass transfer modeling: Approach and application to dynamic hydrothermal processes

    International Nuclear Information System (INIS)

    Janecky, D.R.

    1988-01-01

    A computational modeling code (EQPSreverse arrowS) has been developed to examine sulfur isotopic distribution pathways coupled with calculations of chemical mass transfer pathways. A post processor approach to EQ6 calculations was chosen so that a variety of isotopic pathways could be examined for each reaction pathway. Two types of major bounding conditions were implemented: (1) equilibrium isotopic exchange between sulfate and sulfide species or exchange only accompanying chemical reduction and oxidation events, and (2) existence or lack of isotopic exchange between solution species and precipitated minerals, parallel to the open and closed chemical system formulations of chemical mass transfer modeling codes. All of the chemical data necessary to explicitly calculate isotopic distribution pathways is generated by most mass transfer modeling codes and can be input to the EQPS code. Routines are built in to directly handle EQ6 tabular files. Chemical reaction models of seafloor hydrothermal vent processes and accompanying sulfur isotopic distribution pathways illustrate the capabilities of coupling EQPSreverse arrowS with EQ6 calculations, including the extent of differences that can exist due to the isotopic bounding condition assumptions described above. 11 refs., 2 figs

  5. A High Throughput Ambient Mass Spectrometric Approach to Species Identification and Classification from Chemical Fingerprint Signatures

    Science.gov (United States)

    Musah, Rabi A.; Espinoza, Edgard O.; Cody, Robert B.; Lesiak, Ashton D.; Christensen, Earl D.; Moore, Hannah E.; Maleknia, Simin; Drijfhout, Falko P.

    2015-01-01

    A high throughput method for species identification and classification through chemometric processing of direct analysis in real time (DART) mass spectrometry-derived fingerprint signatures has been developed. The method entails introduction of samples to the open air space between the DART ion source and the mass spectrometer inlet, with the entire observed mass spectral fingerprint subjected to unsupervised hierarchical clustering processing. A range of both polar and non-polar chemotypes are instantaneously detected. The result is identification and species level classification based on the entire DART-MS spectrum. Here, we illustrate how the method can be used to: (1) distinguish between endangered woods regulated by the Convention for the International Trade of Endangered Flora and Fauna (CITES) treaty; (2) assess the origin and by extension the properties of biodiesel feedstocks; (3) determine insect species from analysis of puparial casings; (4) distinguish between psychoactive plants products; and (5) differentiate between Eucalyptus species. An advantage of the hierarchical clustering approach to processing of the DART-MS derived fingerprint is that it shows both similarities and differences between species based on their chemotypes. Furthermore, full knowledge of the identities of the constituents contained within the small molecule profile of analyzed samples is not required. PMID:26156000

  6. The charged Higgs boson mass of the MSSM in the Feynman-diagrammatic approach

    Energy Technology Data Exchange (ETDEWEB)

    Frank, M. [Karlsruhe Univ. (Germany). Inst. fuer Theoretische Physik; Galeta, L.; Heinemeyer, S. [Instituto de Fisica de Cantabria (CSIC-UC), Santander (Spain); Hahn, T.; Hollik, W. [Max-Planck-Institut fuer Physik (Werner-Heisenberg-Institut), Muenchen (Germany); Rzehak, H. [CERN, Geneva (Switzerland); Weiglein, G. [Deutsches Elektronen-Synchrotron (DESY), Hamburg (Germany)

    2013-06-15

    The interpretation of the Higgs signal at {proportional_to}126 GeV within the Minimal Supersymmetric Standard Model (MSSM) depends crucially on the predicted properties of the other Higgs states of the model, as the mass of the charged Higgs boson, M{sub H}{sup {sub {+-}}}. This mass is calculated in the Feynman-diagrammatic approach within the MSSM with real parameters. The result includes the complete one-loop contributions and the two-loop contributions of O({alpha}{sub t}{alpha}{sub s}). The one-loop contributions lead to sizable shifts in the M{sub H}{sup {sub {+-}}} prediction, reaching up to {proportional_to}8 GeV for relatively small values of M{sub A}. Even larger effects can occur depending on the sign and size of the {mu} parameter that enters the corrections affecting the relation between the bottom-quark mass and the bottom Yukawa coupling. The two-loop O({alpha}{sub t}{alpha}{sub s}) terms can shift M{sub H}{sup {sub {+-}}} by more than 2 GeV. The two-loop contributions amount to typically about 30% of the one-loop corrections for the examples that we have studied. These effects can be relevant for precision analyses of the charged MSSM Higgs boson.

  7. A mass balance approach to investigate arsenic cycling in a petroleum plume.

    Science.gov (United States)

    Ziegler, Brady A; Schreiber, Madeline E; Cozzarelli, Isabelle M; Crystal Ng, G-H

    2017-12-01

    Natural attenuation of organic contaminants in groundwater can give rise to a series of complex biogeochemical reactions that release secondary contaminants to groundwater. In a crude oil contaminated aquifer, biodegradation of petroleum hydrocarbons is coupled with the reduction of ferric iron (Fe(III)) hydroxides in aquifer sediments. As a result, naturally occurring arsenic (As) adsorbed to Fe(III) hydroxides in the aquifer sediment is mobilized from sediment into groundwater. However, Fe(III) in sediment of other zones of the aquifer has the capacity to attenuate dissolved As via resorption. In order to better evaluate how long-term biodegradation coupled with Fe-reduction and As mobilization can redistribute As mass in contaminated aquifer, we quantified mass partitioning of Fe and As in the aquifer based on field observation data. Results show that Fe and As are spatially correlated in both groundwater and aquifer sediments. Mass partitioning calculations demonstrate that 99.9% of Fe and 99.5% of As are associated with aquifer sediment. The sediments act as both sources and sinks for As, depending on the redox conditions in the aquifer. Calculations reveal that at least 78% of the original As in sediment near the oil has been mobilized into groundwater over the 35-year lifespan of the plume. However, the calculations also show that only a small percentage of As (∼0.5%) remains in groundwater, due to resorption onto sediment. At the leading edge of the plume, where groundwater is suboxic, sediments sequester Fe and As, causing As to accumulate to concentrations 5.6 times greater than background concentrations. Current As sinks can serve as future sources of As as the plume evolves over time. The mass balance approach used in this study can be applied to As cycling in other aquifers where groundwater As results from biodegradation of an organic carbon point source coupled with Fe reduction. Copyright © 2017 Elsevier Ltd. All rights reserved.

  8. FIRST DETERMINATION OF THE TRUE MASS OF CORONAL MASS EJECTIONS: A NOVEL APPROACH TO USING THE TWO STEREO VIEWPOINTS

    International Nuclear Information System (INIS)

    Colaninno, Robin C.; Vourlidas, Angelos

    2009-01-01

    The twin Sun Earth Connection Coronal and Heliospheric Investigation (SECCHI) COR2 coronagraphs of the Solar Terrestrial Relations Observatory (STEREO) provide images of the solar corona from two viewpoints in the solar system. Since their launch in late 2006, the STEREO Ahead (A) and Behind (B) spacecraft have been slowly separating from Earth at a rate of 22. 0 5 per year. By the end of 2007, the two spacecraft were separated by more than 40 deg. from each other. At that time, we began to see large-scale differences in the morphology and total intensity between coronal mass ejections (CMEs) observed with SECCHI-COR2 on STEREO-A and B. Due to the effects of the Thomson scattering geometry, the intensity of an observed CME is dependent on the angle it makes with the observed plane of the sky. From the intensity images, we can calculate the integrated line-of-sight electron density and mass. We demonstrate that it is possible to simultaneously derive the direction and true total mass of the CME if we make the simple assumption that the same mass should be observed in COR2-A and B.

  9. Improved EDELWEISS-III sensitivity for low-mass WIMPs using a profile likelihood approach

    Energy Technology Data Exchange (ETDEWEB)

    Hehn, L. [Karlsruher Institut fuer Technologie, Institut fuer Kernphysik, Karlsruhe (Germany); Armengaud, E.; Boissiere, T. de; Gros, M.; Navick, X.F.; Nones, C.; Paul, B. [CEA Saclay, DSM/IRFU, Gif-sur-Yvette Cedex (France); Arnaud, Q. [Univ Lyon, Universite Claude Bernard Lyon 1, CNRS/IN2P3, Institut de Physique Nucleaire de Lyon, Lyon (France); Queen' s University, Kingston (Canada); Augier, C.; Billard, J.; Cazes, A.; Charlieux, F.; Jesus, M. de; Gascon, J.; Juillard, A.; Queguiner, E.; Sanglard, V.; Vagneron, L. [Univ Lyon, Universite Claude Bernard Lyon 1, CNRS/IN2P3, Institut de Physique Nucleaire de Lyon, Lyon (France); Benoit, A.; Camus, P. [Institut Neel, CNRS/UJF, Grenoble (France); Berge, L.; Chapellier, M.; Dumoulin, L.; Giuliani, A.; Le-Sueur, H.; Marnieros, S.; Olivieri, E.; Poda, D. [CSNSM, Univ. Paris-Sud, CNRS/IN2P3, Universite Paris-Saclay, Orsay (France); Bluemer, J. [Karlsruher Institut fuer Technologie, Institut fuer Kernphysik, Karlsruhe (Germany); Karlsruher Institut fuer Technologie, Institut fuer Experimentelle Kernphysik, Karlsruhe (Germany); Broniatowski, A. [CSNSM, Univ. Paris-Sud, CNRS/IN2P3, Universite Paris-Saclay, Orsay (France); Karlsruher Institut fuer Technologie, Institut fuer Experimentelle Kernphysik, Karlsruhe (Germany); Eitel, K.; Kozlov, V.; Siebenborn, B. [Karlsruher Institut fuer Technologie, Institut fuer Kernphysik, Karlsruhe (Germany); Foerster, N.; Heuermann, G.; Scorza, S. [Karlsruher Institut fuer Technologie, Institut fuer Experimentelle Kernphysik, Karlsruhe (Germany); Jin, Y. [Laboratoire de Photonique et de Nanostructures, CNRS, Route de Nozay, Marcoussis (France); Kefelian, C. [Univ Lyon, Universite Claude Bernard Lyon 1, CNRS/IN2P3, Institut de Physique Nucleaire de Lyon, Lyon (France); Karlsruher Institut fuer Technologie, Institut fuer Experimentelle Kernphysik, Karlsruhe (Germany); Kleifges, M.; Tcherniakhovski, D.; Weber, M. [Karlsruher Institut fuer Technologie, Institut fuer Prozessdatenverarbeitung und Elektronik, Karlsruhe (Germany); Kraus, H. [University of Oxford, Department of Physics, Oxford (United Kingdom); Kudryavtsev, V.A. [University of Sheffield, Department of Physics and Astronomy, Sheffield (United Kingdom); Pari, P. [CEA Saclay, DSM/IRAMIS, Gif-sur-Yvette (France); Piro, M.C. [CSNSM, Univ. Paris-Sud, CNRS/IN2P3, Universite Paris-Saclay, Orsay (France); Rensselaer Polytechnic Institute, Troy, NY (United States); Rozov, S.; Yakushev, E. [JINR, Laboratory of Nuclear Problems, Dubna, Moscow Region (Russian Federation); Schmidt, B. [Karlsruher Institut fuer Technologie, Institut fuer Kernphysik, Karlsruhe (Germany); Lawrence Berkeley National Laboratory, Berkeley, CA (United States)

    2016-10-15

    We report on a dark matter search for a Weakly Interacting Massive Particle (WIMP) in the mass range m{sub χ} element of [4, 30] GeV/c{sup 2} with the EDELWEISS-III experiment. A 2D profile likelihood analysis is performed on data from eight selected detectors with the lowest energy thresholds leading to a combined fiducial exposure of 496 kg-days. External backgrounds from γ- and β-radiation, recoils from {sup 206}Pb and neutrons as well as detector intrinsic backgrounds were modelled from data outside the region of interest and constrained in the analysis. The basic data selection and most of the background models are the same as those used in a previously published analysis based on boosted decision trees (BDT) [1]. For the likelihood approach applied in the analysis presented here, a larger signal efficiency and a subtraction of the expected background lead to a higher sensitivity, especially for the lowest WIMP masses probed. No statistically significant signal was found and upper limits on the spin-independent WIMP-nucleon scattering cross section can be set with a hypothesis test based on the profile likelihood test statistics. The 90 % C.L. exclusion limit set for WIMPs with m{sub χ} = 4 GeV/c{sup 2} is 1.6 x 10{sup -39} cm{sup 2}, which is an improvement of a factor of seven with respect to the BDT-based analysis. For WIMP masses above 15 GeV/c{sup 2} the exclusion limits found with both analyses are in good agreement. (orig.)

  10. Simple, empirical approach to predict neutron capture cross sections from nuclear masses

    Science.gov (United States)

    Couture, A.; Casten, R. F.; Cakirli, R. B.

    2017-12-01

    Background: Neutron capture cross sections are essential to understanding the astrophysical s and r processes, the modeling of nuclear reactor design and performance, and for a wide variety of nuclear forensics applications. Often, cross sections are needed for nuclei where experimental measurements are difficult. Enormous effort, over many decades, has gone into attempting to develop sophisticated statistical reaction models to predict these cross sections. Such work has met with some success but is often unable to reproduce measured cross sections to better than 40 % , and has limited predictive power, with predictions from different models rapidly differing by an order of magnitude a few nucleons from the last measurement. Purpose: To develop a new approach to predicting neutron capture cross sections over broad ranges of nuclei that accounts for their values where known and which has reliable predictive power with small uncertainties for many nuclei where they are unknown. Methods: Experimental neutron capture cross sections were compared to empirical mass observables in regions of similar structure. Results: We present an extremely simple method, based solely on empirical mass observables, that correlates neutron capture cross sections in the critical energy range from a few keV to a couple hundred keV. We show that regional cross sections are compactly correlated in medium and heavy mass nuclei with the two-neutron separation energy. These correlations are easily amenable to predict unknown cross sections, often converting the usual extrapolations to more reliable interpolations. It almost always reproduces existing data to within 25 % and estimated uncertainties are below about 40 % up to 10 nucleons beyond known data. Conclusions: Neutron capture cross sections display a surprisingly strong connection to the two-neutron separation energy, a nuclear structure property. The simple, empirical correlations uncovered provide model-independent predictions of

  11. Tribocorrosion in pressurized high temperature water: a mass flow model based on the third body approach

    Energy Technology Data Exchange (ETDEWEB)

    Guadalupe Maldonado, S.

    2014-07-01

    Pressurized water reactors (PWR) used for power generation are operated at elevated temperatures (280-300 °C) and under higher pressure (120-150 bar). In addition to these harsh environmental conditions some components of the PWR assemblies are subject to mechanical loading (sliding, vibration and impacts) leading to undesirable and hardly controllable material degradation phenomena. In such situations wear is determined by the complex interplay (tribocorrosion) between mechanical, material and physical-chemical phenomena. Tribocorrosion in PWR conditions is at present little understood and models need to be developed in order to predict component lifetime over several decades. The goal of this project, carried out in collaboration with the French company AREVA NP, is to develop a predictive model based on the mechanistic understanding of tribocorrosion of specific PWR components (stainless steel control assemblies, stellite grippers). The approach taken here is to describe degradation in terms of electro-chemical and mechanical material flows (third body concept of tribology) from the metal into the friction film (i.e. the oxidized film forming during rubbing on the metal surface) and from the friction film into the environment instead of simple mass loss considerations. The project involves the establishment of mechanistic models for describing the single flows based on ad-hoc tribocorrosion measurements operating at low temperature. The overall behaviour at high temperature and pressure in investigated using a dedicated tribometer (Aurore) including electrochemical control of the contact during rubbing. Physical laws describing the individual flows according to defined mechanisms and as a function of defined physical parameters were identified based on the obtained experimental results and from literature data. The physical laws were converted into mass flow rates and solved as differential equation system by considering the mass balance in compartments

  12. Challenges ahead for mass spectrometry and proteomics applications in epigenetics.

    Science.gov (United States)

    Kessler, Benedikt M

    2010-02-01

    Inheritance of biological information to future generations depends on the replication of DNA and the Mendelian principle of distribution of genes. In addition, external and environmental factors can influence traits that can be propagated to offspring, but the molecular details of this are only beginning to be understood. The discoveries of DNA methylation and post-translational modifications on chromatin and histones provided entry points for regulating gene expression, an area now defined as epigenetics and epigenomics. Mass spectrometry turned out to be instrumental in uncovering molecular details involved in these processes. The central role of histone post-translational modifications in epigenetics related biological processes has revitalized mass spectrometry based investigations. In this special report, current approaches and future challenges that lay ahead due to the enormous complexity are discussed.

  13. Extensive characterization of Tupaia belangeri neuropeptidome using an integrated mass spectrometric approach.

    Science.gov (United States)

    Petruzziello, Filomena; Fouillen, Laetitia; Wadensten, Henrik; Kretz, Robert; Andren, Per E; Rainer, Gregor; Zhang, Xiaozhe

    2012-02-03

    Neuropeptidomics is used to characterize endogenous peptides in the brain of tree shrews (Tupaia belangeri). Tree shrews are small animals similar to rodents in size but close relatives of primates, and are excellent models for brain research. Currently, tree shrews have no complete proteome information available on which direct database search can be allowed for neuropeptide identification. To increase the capability in the identification of neuropeptides in tree shrews, we developed an integrated mass spectrometry (MS)-based approach that combines methods including data-dependent, directed, and targeted liquid chromatography (LC)-Fourier transform (FT)-tandem MS (MS/MS) analysis, database construction, de novo sequencing, precursor protein search, and homology analysis. Using this integrated approach, we identified 107 endogenous peptides that have sequences identical or similar to those from other mammalian species. High accuracy MS and tandem MS information, with BLAST analysis and chromatographic characteristics were used to confirm the sequences of all the identified peptides. Interestingly, further sequence homology analysis demonstrated that tree shrew peptides have a significantly higher degree of homology to equivalent sequences in humans than those in mice or rats, consistent with the close phylogenetic relationship between tree shrews and primates. Our results provide the first extensive characterization of the peptidome in tree shrews, which now permits characterization of their function in nervous and endocrine system. As the approach developed fully used the conservative properties of neuropeptides in evolution and the advantage of high accuracy MS, it can be portable for identification of neuropeptides in other species for which the fully sequenced genomes or proteomes are not available.

  14. Improvement of a sample preparation method assisted by sodium deoxycholate for mass-spectrometry-based shotgun membrane proteomics.

    Science.gov (United States)

    Lin, Yong; Lin, Haiyan; Liu, Zhonghua; Wang, Kunbo; Yan, Yujun

    2014-11-01

    In current shotgun-proteomics-based biological discovery, the identification of membrane proteins is a challenge. This is especially true for integral membrane proteins due to their highly hydrophobic nature and low abundance. Thus, much effort has been directed at sample preparation strategies such as use of detergents, chaotropes, and organic solvents. We previously described a sample preparation method for shotgun membrane proteomics, the sodium deoxycholate assisted method, which cleverly circumvents many of the challenges associated with traditional sample preparation methods. However, the method is associated with significant sample loss due to the slightly weaker extraction/solubilization ability of sodium deoxycholate when it is used at relatively low concentrations such as 1%. Hence, we present an enhanced sodium deoxycholate sample preparation strategy that first uses a high concentration of sodium deoxycholate (5%) to lyse membranes and extract/solubilize hydrophobic membrane proteins, and then dilutes the detergent to 1% for a more efficient digestion. We then applied the improved method to shotgun analysis of proteins from rat liver membrane enriched fraction. Compared with other representative sample preparation strategies including our previous sodium deoxycholate assisted method, the enhanced sodium deoxycholate method exhibited superior sensitivity, coverage, and reliability for the identification of membrane proteins particularly those with high hydrophobicity and/or multiple transmembrane domains. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  15. Chemical deamidation: a common pitfall in large-scale N-linked glycoproteomic mass spectrometry-based analyses

    DEFF Research Database (Denmark)

    Palmisano, Giuseppe; Melo-Braga, Marcella Nunes; Engholm-Keller, Kasper

    2012-01-01

    for false positives. The confusion arises since the protein N-glycosidase F (PNGase F) reaction used to separate N-glycans from formerly glycosylated peptides catalyses the cleavage and deamidates the asparagine residue. This is typically viewed as beneficial since it acts to highlight the modification site......-linked consensus sites based on common N-linked glycoproteomics strategies without proper control experiments. Beside showing the spontaneous deamidation we provide alternative methods for validation that should be used in such experiments....

  16. Fast and Simple Protocols for Mass Spectrometry-Based Proteomics of Small Fresh Frozen Uterine Tissue Sections

    NARCIS (Netherlands)

    Dapic, I.; Uwugiaren, N.; Jansen, P.J.; Corthals, G.L.

    2017-01-01

    Human tissues are an important link between organ-specific spatial molecular information, patient pathology, and patient treatment options. However, patient tissues are uniquely obtained by time and location, and limited in their availability and size. Currently, little knowledge exists about

  17. Covalent surface modification of prions: a mass spectrometry-based means of detecting distinctive structural features of prion strains

    Science.gov (United States)

    Prions (PrPSc) are molecular pathogens that are able to convert the isosequential normal cellular prion protein (PrPC) into a prion. The only demonstrated differences between PrPC and PrPSc is conformational, they are isoforms. A given host can be infected by more than one kind or strain of prion. F...

  18. Reproducibility of mass spectrometry based protein profiles for diagnosis of ovarian cancer across clinical studies: A systematic review

    DEFF Research Database (Denmark)

    Callesen, AK; Mogensen, O; Jensen, AK

    2012-01-01

    of published discriminatory peaks to peaks found in an original MALDI MS protein profiling study was made to address the key question of reproducibility across studies. An overlap was found despite substantial heterogeneity between studies relating to study design, biological material, pre-analytical treatment...

  19. THE PANCHROMATIC HUBBLE ANDROMEDA TREASURY. IV. A PROBABILISTIC APPROACH TO INFERRING THE HIGH-MASS STELLAR INITIAL MASS FUNCTION AND OTHER POWER-LAW FUNCTIONS

    Energy Technology Data Exchange (ETDEWEB)

    Weisz, Daniel R.; Fouesneau, Morgan; Dalcanton, Julianne J.; Clifton Johnson, L.; Beerman, Lori C.; Williams, Benjamin F. [Department of Astronomy, University of Washington, Box 351580, Seattle, WA 98195 (United States); Hogg, David W.; Foreman-Mackey, Daniel T. [Center for Cosmology and Particle Physics, New York University, 4 Washington Place, New York, NY 10003 (United States); Rix, Hans-Walter; Gouliermis, Dimitrios [Max Planck Institute for Astronomy, Koenigstuhl 17, D-69117 Heidelberg (Germany); Dolphin, Andrew E. [Raytheon Company, 1151 East Hermans Road, Tucson, AZ 85756 (United States); Lang, Dustin [Department of Astrophysical Sciences, Princeton University, Princeton, NJ 08544 (United States); Bell, Eric F. [Department of Astronomy, University of Michigan, 500 Church Street, Ann Arbor, MI 48109 (United States); Gordon, Karl D.; Kalirai, Jason S. [Space Telescope Science Institute, 3700 San Martin Drive, Baltimore, MD 21218 (United States); Skillman, Evan D., E-mail: dweisz@astro.washington.edu [Minnesota Institute for Astrophysics, University of Minnesota, 116 Church Street SE, Minneapolis, MN 55455 (United States)

    2013-01-10

    We present a probabilistic approach for inferring the parameters of the present-day power-law stellar mass function (MF) of a resolved young star cluster. This technique (1) fully exploits the information content of a given data set; (2) can account for observational uncertainties in a straightforward way; (3) assigns meaningful uncertainties to the inferred parameters; (4) avoids the pitfalls associated with binning data; and (5) can be applied to virtually any resolved young cluster, laying the groundwork for a systematic study of the high-mass stellar MF (M {approx}> 1 M {sub Sun }). Using simulated clusters and Markov Chain Monte Carlo sampling of the probability distribution functions, we show that estimates of the MF slope, {alpha}, are unbiased and that the uncertainty, {Delta}{alpha}, depends primarily on the number of observed stars and on the range of stellar masses they span, assuming that the uncertainties on individual masses and the completeness are both well characterized. Using idealized mock data, we compute the theoretical precision, i.e., lower limits, on {alpha}, and provide an analytic approximation for {Delta}{alpha} as a function of the observed number of stars and mass range. Comparison with literature studies shows that {approx}3/4 of quoted uncertainties are smaller than the theoretical lower limit. By correcting these uncertainties to the theoretical lower limits, we find that the literature studies yield ({alpha}) = 2.46, with a 1{sigma} dispersion of 0.35 dex. We verify that it is impossible for a power-law MF to obtain meaningful constraints on the upper mass limit of the initial mass function, beyond the lower bound of the most massive star actually observed. We show that avoiding substantial biases in the MF slope requires (1) including the MF as a prior when deriving individual stellar mass estimates, (2) modeling the uncertainties in the individual stellar masses, and (3) fully characterizing and then explicitly modeling the

  20. The Panchromatic Hubble Andromeda Treasury. IV. A Probabilistic Approach to Inferring the High-mass Stellar Initial Mass Function and Other Power-law Functions

    Science.gov (United States)

    Weisz, Daniel R.; Fouesneau, Morgan; Hogg, David W.; Rix, Hans-Walter; Dolphin, Andrew E.; Dalcanton, Julianne J.; Foreman-Mackey, Daniel T.; Lang, Dustin; Johnson, L. Clifton; Beerman, Lori C.; Bell, Eric F.; Gordon, Karl D.; Gouliermis, Dimitrios; Kalirai, Jason S.; Skillman, Evan D.; Williams, Benjamin F.

    2013-01-01

    We present a probabilistic approach for inferring the parameters of the present-day power-law stellar mass function (MF) of a resolved young star cluster. This technique (1) fully exploits the information content of a given data set; (2) can account for observational uncertainties in a straightforward way; (3) assigns meaningful uncertainties to the inferred parameters; (4) avoids the pitfalls associated with binning data; and (5) can be applied to virtually any resolved young cluster, laying the groundwork for a systematic study of the high-mass stellar MF (M >~ 1 M ⊙). Using simulated clusters and Markov Chain Monte Carlo sampling of the probability distribution functions, we show that estimates of the MF slope, α, are unbiased and that the uncertainty, Δα, depends primarily on the number of observed stars and on the range of stellar masses they span, assuming that the uncertainties on individual masses and the completeness are both well characterized. Using idealized mock data, we compute the theoretical precision, i.e., lower limits, on α, and provide an analytic approximation for Δα as a function of the observed number of stars and mass range. Comparison with literature studies shows that ~3/4 of quoted uncertainties are smaller than the theoretical lower limit. By correcting these uncertainties to the theoretical lower limits, we find that the literature studies yield langαrang = 2.46, with a 1σ dispersion of 0.35 dex. We verify that it is impossible for a power-law MF to obtain meaningful constraints on the upper mass limit of the initial mass function, beyond the lower bound of the most massive star actually observed. We show that avoiding substantial biases in the MF slope requires (1) including the MF as a prior when deriving individual stellar mass estimates, (2) modeling the uncertainties in the individual stellar masses, and (3) fully characterizing and then explicitly modeling the completeness for stars of a given mass. The precision on MF

  1. THE PANCHROMATIC HUBBLE ANDROMEDA TREASURY. IV. A PROBABILISTIC APPROACH TO INFERRING THE HIGH-MASS STELLAR INITIAL MASS FUNCTION AND OTHER POWER-LAW FUNCTIONS

    International Nuclear Information System (INIS)

    Weisz, Daniel R.; Fouesneau, Morgan; Dalcanton, Julianne J.; Clifton Johnson, L.; Beerman, Lori C.; Williams, Benjamin F.; Hogg, David W.; Foreman-Mackey, Daniel T.; Rix, Hans-Walter; Gouliermis, Dimitrios; Dolphin, Andrew E.; Lang, Dustin; Bell, Eric F.; Gordon, Karl D.; Kalirai, Jason S.; Skillman, Evan D.

    2013-01-01

    We present a probabilistic approach for inferring the parameters of the present-day power-law stellar mass function (MF) of a resolved young star cluster. This technique (1) fully exploits the information content of a given data set; (2) can account for observational uncertainties in a straightforward way; (3) assigns meaningful uncertainties to the inferred parameters; (4) avoids the pitfalls associated with binning data; and (5) can be applied to virtually any resolved young cluster, laying the groundwork for a systematic study of the high-mass stellar MF (M ∼> 1 M ☉ ). Using simulated clusters and Markov Chain Monte Carlo sampling of the probability distribution functions, we show that estimates of the MF slope, α, are unbiased and that the uncertainty, Δα, depends primarily on the number of observed stars and on the range of stellar masses they span, assuming that the uncertainties on individual masses and the completeness are both well characterized. Using idealized mock data, we compute the theoretical precision, i.e., lower limits, on α, and provide an analytic approximation for Δα as a function of the observed number of stars and mass range. Comparison with literature studies shows that ∼3/4 of quoted uncertainties are smaller than the theoretical lower limit. By correcting these uncertainties to the theoretical lower limits, we find that the literature studies yield (α) = 2.46, with a 1σ dispersion of 0.35 dex. We verify that it is impossible for a power-law MF to obtain meaningful constraints on the upper mass limit of the initial mass function, beyond the lower bound of the most massive star actually observed. We show that avoiding substantial biases in the MF slope requires (1) including the MF as a prior when deriving individual stellar mass estimates, (2) modeling the uncertainties in the individual stellar masses, and (3) fully characterizing and then explicitly modeling the completeness for stars of a given mass. The precision on MF

  2. Depression, body mass index, and chronic obstructive pulmonary disease – a holistic approach

    Directory of Open Access Journals (Sweden)

    Catalfo G

    2016-02-01

    Full Text Available Giuseppe Catalfo,1 Luciana Crea,1 Tiziana Lo Castro,1 Francesca Magnano San Lio,1 Giuseppe Minutolo,1 Gherardo Siscaro,2 Noemi Vaccino,1 Nunzio Crimi,3 Eugenio Aguglia1 1Department of Psychiatry, Policlinico “G. Rodolico” University Hospital, University of Catania, Catania, Italy; 2Operative Unit Neurorehabilitation, IRCCS Fondazione Salvatore Maugeri, Sciacca, Italy; 3Department of Pneumology, Policlinico “G. Rodolico” University Hospital, University of Catania, Catania, Italy Background: Several clinical studies suggest common underlying pathogenetic mechanisms of COPD and depressive/anxiety disorders. We aim to evaluate psychopathological and physical effects of aerobic exercise, proposed in the context of pulmonary rehabilitation, in a sample of COPD patients, through the correlation of some psychopathological variables and physical/pneumological parameters. Methods: Fifty-two consecutive subjects were enrolled. At baseline, the sample was divided into two subgroups consisting of 38 depression-positive and 14 depression-negative subjects according to the Hamilton Depression Rating Scale (HAM-D. After the rehabilitation treatment, we compared psychometric and physical examinations between the two groups. Results: The differences after the rehabilitation program in all assessed parameters demonstrated a significant improvement in psychiatric and pneumological conditions. The reduction of BMI was significantly correlated with fat mass but only in the depression-positive patients. Conclusion: Our results suggest that pulmonary rehabilitation improves depressive and anxiety symptoms in COPD. This improvement is significantly related to the reduction of fat mass and BMI only in depressed COPD patients, in whom these parameters were related at baseline. These findings suggest that depressed COPD patients could benefit from a rehabilitation program in the context of a multidisciplinary approach. Keywords: COPD, depression, aerobic exercise

  3. Integrative Mass Spectrometry Approaches to Monitor Protein Structures, Modifications, and Interactions

    NARCIS (Netherlands)

    Lössl, P.

    2017-01-01

    This thesis illustrates the current standing of mass spectrometry (MS) in molecular and structural biology. The primary aim of the herein described research is to facilitate protein characterization by combining mass spectrometric methods among each other and with complementary analytical

  4. Numerical probabilistic analysis for slope stability in fractured rock masses using DFN-DEM approach

    Directory of Open Access Journals (Sweden)

    Alireza Baghbanan

    2017-06-01

    Full Text Available Due to existence of uncertainties in input geometrical properties of fractures, there is not any unique solution for assessing the stability of slopes in jointed rock masses. Therefore, the necessity of applying probabilistic analysis in these cases is inevitable. In this study a probabilistic analysis procedure together with relevant algorithms are developed using Discrete Fracture Network-Distinct Element Method (DFN-DEM approach. In the right abutment of Karun 4 dam and downstream of the dam body, five joint sets and one major joint have been identified. According to the geometrical properties of fractures in Karun river valley, instability situations are probable in this abutment. In order to evaluate the stability of the rock slope, different combinations of joint set geometrical parameters are selected, and a series of numerical DEM simulations are performed on generated and validated DFN models in DFN-DEM approach to measure minimum required support patterns in dry and saturated conditions. Results indicate that the distribution of required bolt length is well fitted with a lognormal distribution in both circumstances. In dry conditions, the calculated mean value is 1125.3 m, and more than 80 percent of models need only 1614.99 m of bolts which is a bolt pattern with 2 m spacing and 12 m length. However, as for the slopes with saturated condition, the calculated mean value is 1821.8 m, and more than 80 percent of models need only 2653.49 m of bolts which is equivalent to a bolt pattern with 15 m length and 1.5 m spacing. Comparison between obtained results with numerical and empirical method show that investigation of a slope stability with different DFN realizations which conducted in different block patterns is more efficient than the empirical methods.

  5. Predicting polycyclic aromatic hydrocarbons using a mass fraction approach in a geostatistical framework across North Carolina.

    Science.gov (United States)

    Reyes, Jeanette M; Hubbard, Heidi F; Stiegel, Matthew A; Pleil, Joachim D; Serre, Marc L

    2018-01-09

    Currently in the United States there are no regulatory standards for ambient concentrations of polycyclic aromatic hydrocarbons (PAHs), a class of organic compounds with known carcinogenic species. As such, monitoring data are not routinely collected resulting in limited exposure mapping and epidemiologic studies. This work develops the log-mass fraction (LMF) Bayesian maximum entropy (BME) geostatistical prediction method used to predict the concentration of nine particle-bound PAHs across the US state of North Carolina. The LMF method develops a relationship between a relatively small number of collocated PAH and fine Particulate Matter (PM2.5) samples collected in 2005 and applies that relationship to a larger number of locations where PM2.5 is routinely monitored to more broadly estimate PAH concentrations across the state. Cross validation and mapping results indicate that by incorporating both PAH and PM2.5 data, the LMF BME method reduces mean squared error by 28.4% and produces more realistic spatial gradients compared to the traditional kriging approach based solely on observed PAH data. The LMF BME method efficiently creates PAH predictions in a PAH data sparse and PM2.5 data rich setting, opening the door for more expansive epidemiologic exposure assessments of ambient PAH.

  6. Quantifying in-stream retention of nitrate at catchment scales using a practical mass balance approach.

    Science.gov (United States)

    Schwientek, Marc; Selle, Benny

    2016-02-01

    As field data on in-stream nitrate retention is scarce at catchment scales, this study aimed at quantifying net retention of nitrate within the entire river network of a fourth-order stream. For this purpose, a practical mass balance approach combined with a Lagrangian sampling scheme was applied and seasonally repeated to estimate daily in-stream net retention of nitrate for a 17.4 km long, agriculturally influenced, segment of the Steinlach River in southwestern Germany. This river segment represents approximately 70% of the length of the main stem and about 32% of the streambed area of the entire river network. Sampling days in spring and summer were biogeochemically more active than in autumn and winter. Results obtained for the main stem of Steinlach River were subsequently extrapolated to the stream network in the catchment. It was demonstrated that, for baseflow conditions in spring and summer, in-stream nitrate retention could sum up to a relevant term of the catchment's nitrogen balance if the entire stream network was considered.

  7. Capillary-HPLC with tandem mass spectrometry in analysis of alkaloid dyestuffs - a new approach.

    Science.gov (United States)

    Dąbrowski, Damian; Lech, Katarzyna; Jarosz, Maciej

    2018-05-01

    Development of the identification method of alkaloid compounds in Amur cork tree as well as not examined so far Oregon grape and European Barberry shrubs are presented. The novel approach to separation of alkaloids was applied and the capillary-high-performance liquid chromatography (capillary-HPLC) system was used, which has never previously been reported for alkaloid-based dyestuffs analysis. Its optimization was conducted with three different stationary phases (unmodified octadecylsilane-bonded silica, octadecylsilane modified with polar groups and silica-bonded pentaflourophenyls) as well as with different solvent buffers. Detection of the isolated compounds was carried out using diode-array detector (DAD) and tandem mass spectrometer with electrospray ionization (ESI MS/MS). The working parameters of ESI were optimized, whereas the multiple reactions monitoring (MRM) parameters of MS/MS detection were chosen based on the product ion spectra of the quasi-molecular ions. Calibration curve of berberine has been estimated (y = 1712091x + 4785.03 with the correlation coefficient 0.9999). Limit of detection and limit of quantification were calculated to be 3.2 and 9.7 ng/mL, respectively. Numerous alkaloids (i.e., berberine, jatrorrhizine and magnoflorine, as well as phellodendrine, menisperine and berbamine) were identified in the extracts from alkaloid plants and silk and wool fibers dyed with these dyestuffs, among them their markers. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  8. Identification and Quantitation of Biomarkers for Radiation-Induced Injury via Mass Spectrometry

    Science.gov (United States)

    Jones, Jace W.; Scott, Alison J.; Tudor, Gregory; Xu, Pu-Ting; Jackson, Isabel L.; Vujaskovic, Zeljko; Booth, Catherine; MacVittie, Thomas J.; Ernst, Robert K.; Kane, Maureen A.

    2013-01-01

    Biomarker identification and validation for radiation exposure is a rapidly expanding field encompassing the need for well-defined animal models and advanced analytical techniques. The resources within the consortium, Medical Countermeasures Against Radiological Threats (MCART), provide a unique opportunity for accessing well-defined animal models that simulate the key sequelae of the acute radiation syndrome and the delayed effects of acute radiation exposure. Likewise, the use of mass spectrometry-based analytical techniques for biomarker discovery and validation enables a robust analytical platform that is amenable to a variety of sample matrices and considered the benchmark for bio-molecular identification and quantitation. Herein, we demonstrate the use of two targeted mass spectrometry approaches to link established MCART animal models to identified metabolite biomarkers. Circulating citrulline concentration was correlated to gross histological gastrointestinal tissue damage and retinoic acid production in lung tissue was established to be reduced at early and late time points post high dose irradiation. Going forward, the use of mass spectrometry-based metabolomics coupled to well-defined animal models provides the unique opportunity for comprehensive biomarker discovery. PMID:24276554

  9. Searching for intermediate-mass black holes in galaxies with low-luminosity AGN: a multiple-method approach

    Science.gov (United States)

    Koliopanos, F.; Ciambur, B.; Graham, A.; Webb, N.; Coriat, M.; Mutlu-Pakdil, B.; Davis, B.; Godet, O.; Barret, D.; Seigar, M.

    2017-10-01

    Intermediate Mass Black Holes (IMBHs) are predicted by a variety of models and are the likely seeds for super massive BHs (SMBHs). However, we have yet to establish their existence. One method, by which we can discover IMBHs, is by measuring the mass of an accreting BH, using X-ray and radio observations and drawing on the correlation between radio luminosity, X-ray luminosity and the BH mass, known as the fundamental plane of BH activity (FP-BH). Furthermore, the mass of BHs in the centers of galaxies, can be estimated using scaling relations between BH mass and galactic properties. We are initiating a campaign to search for IMBH candidates in dwarf galaxies with low-luminosity AGN, using - for the first time - three different scaling relations and the FP-BH, simultaneously. In this first stage of our campaign, we measure the mass of seven LLAGN, that have been previously suggested to host central IMBHs, investigate the consistency between the predictions of the BH scaling relations and the FP-BH, in the low mass regime and demonstrate that this multiple method approach provides a robust average mass prediction. In my talk, I will discuss our methodology, results and next steps of this campaign.

  10. Time-dependent mass of cosmological perturbations in the hybrid and dressed metric approaches to loop quantum cosmology

    Science.gov (United States)

    Elizaga Navascués, Beatriz; Martín de Blas, Daniel; Mena Marugán, Guillermo A.

    2018-02-01

    Loop quantum cosmology has recently been applied in order to extend the analysis of primordial perturbations to the Planck era and discuss the possible effects of quantum geometry on the cosmic microwave background. Two approaches to loop quantum cosmology with admissible ultraviolet behavior leading to predictions that are compatible with observations are the so-called hybrid and dressed metric approaches. In spite of their similarities and relations, we show in this work that the effective equations that they provide for the evolution of the tensor and scalar perturbations are somewhat different. When backreaction is neglected, the discrepancy appears only in the time-dependent mass term of the corresponding field equations. We explain the origin of this difference, arising from the distinct quantization procedures. Besides, given the privileged role that the big bounce plays in loop quantum cosmology, e.g. as a natural instant of time to set initial conditions for the perturbations, we also analyze the positivity of the time-dependent mass when this bounce occurs. We prove that the mass of the tensor perturbations is positive in the hybrid approach when the kinetic contribution to the energy density of the inflaton dominates over its potential, as well as for a considerably large sector of backgrounds around that situation, while this mass is always nonpositive in the dressed metric approach. Similar results are demonstrated for the scalar perturbations in a sector of background solutions that includes the kinetically dominated ones; namely, the mass then is positive for the hybrid approach, whereas it typically becomes negative in the dressed metric case. More precisely, this last statement is strictly valid when the potential is quadratic for values of the inflaton mass that are phenomenologically favored.

  11. Structure identification by Mass Spectrometry Non-Targeted Analysis using the US EPA’s CompTox Chemistry Dashboard

    Science.gov (United States)

    Identification of unknowns in mass spectrometry based non-targeted analyses (NTA) requires the integration of complementary pieces of data to arrive at a confident, consensus structure. Researchers use chemical reference databases, spectral matching, fragment prediction tools, r...

  12. Mass spectrometry techniques in the survey of steroid metabolites as potential disease biomarkers: a review.

    Science.gov (United States)

    Gouveia, Maria João; Brindley, Paul J; Santos, Lúcio Lara; Correia da Costa, José Manuel; Gomes, Paula; Vale, Nuno

    2013-09-01

    Mass spectrometric approaches have been fundamental to the identification of metabolites associated with steroid hormones, yet this topic has not been reviewed in depth in recent years. To this end, and given the increasing relevance of liquid chromatography-mass spectrometry (LC-MS) studies on steroid hormones and their metabolites, the present review addresses this subject. This review provides a timely summary of the use of various mass spectrometry-based analytical techniques during the evaluation of steroidal biomarkers in a range of human disease settings. The sensitivity and specificity of these technologies are clearly providing valuable new insights into breast cancer and cardiovascular disease. We aim to contribute to an enhanced understanding of steroid metabolism and how it can be profiled by LC-MS techniques. Crown Copyright © 2013. Published by Elsevier Inc. All rights reserved.

  13. Identification of hemoglobin variants by top-down mass spectrometry using selected diagnostic product ions.

    Science.gov (United States)

    Coelho Graça, Didia; Hartmer, Ralf; Jabs, Wolfgang; Beris, Photis; Clerici, Lorella; Stoermer, Carsten; Samii, Kaveh; Hochstrasser, Denis; Tsybin, Yury O; Scherl, Alexander; Lescuyer, Pierre

    2015-04-01

    Hemoglobin disorder diagnosis is a complex procedure combining several analytical steps. Due to the lack of specificity of the currently used protein analysis methods, the identification of uncommon hemoglobin variants (proteoforms) can become a hard task to accomplish. The aim of this work was to develop a mass spectrometry-based approach to quickly identify mutated protein sequences within globin chain variants. To reach this goal, a top-down electron transfer dissociation mass spectrometry method was developed for hemoglobin β chain analysis. A diagnostic product ion list was established with a color code strategy allowing to quickly and specifically localize a mutation in the hemoglobin β chain sequence. The method was applied to the analysis of rare hemoglobin β chain variants and an (A)γ-β fusion protein. The results showed that the developed data analysis process allows fast and reliable interpretation of top-down electron transfer dissociation mass spectra by nonexpert users in the clinical area.

  14. A High Throughput Ambient Mass Spectrometric Approach to Species Identification and Classification from Chemical Fingerprint Signatures

    OpenAIRE

    Musah, Rabi A.; Espinoza, Edgard O.; Cody, Robert B.; Lesiak, Ashton D.; Christensen, Earl D.; Moore, Hannah E.; Maleknia, Simin; Drijfhout, Falko P.

    2015-01-01

    A high throughput method for species identification and classification through chemometric processing of direct analysis in real time (DART) mass spectrometry-derived fingerprint signatures has been developed. The method entails introduction of samples to the open air space between the DART ion source and the mass spectrometer inlet, with the entire observed mass spectral fingerprint subjected to unsupervised hierarchical clustering processing. A range of both polar and non-polar chemotypes a...

  15. Targeted metabolite profile of food bioactive compounds by Orbitrap high resolution mass spectrometry: The 'FancyTiles' approach

    NARCIS (Netherlands)

    Troise, A.D.; Ferracane, R.; Palermo, M.; Fogliano, V.

    2014-01-01

    In this paper a new targeted metabolic profile approach using Orbitrap high resolution mass spectrometry was described. For each foodmatrix various classes of bioactive compounds and some specificmetabolites of interest were selected on the basis of the existing knowledge creating an easy-to-read

  16. Developing a discrimination rule between breast cancer patients and controls using proteomics mass spectrometric data: A three-step approach

    NARCIS (Netherlands)

    Heidema, A.G.; Nagelkerke, N.

    2008-01-01

    To discriminate between breast cancer patients and controls, we used a three-step approach to obtain our decision rule. First, we ranked the mass/charge values using random forests, because it generates importance indices that take possible interactions into account. We observed that the top ranked

  17. Statistically optimal estimation of Greenland Ice Sheet mass variations from GRACE monthly solutions using an improved mascon approach

    NARCIS (Netherlands)

    Ran, J.; Ditmar, P.G.; Klees, R.; Farahani, H.

    2017-01-01

    We present an improved mascon approach to transform monthly spherical harmonic solutions based on GRACE satellite data into mass anomaly estimates in Greenland. The GRACE-based spherical harmonic coefficients are used to synthesize gravity anomalies at satellite altitude, which are then inverted

  18. A deep learning approach for the analysis of masses in mammograms with minimal user intervention.

    Science.gov (United States)

    Dhungel, Neeraj; Carneiro, Gustavo; Bradley, Andrew P

    2017-04-01

    We present an integrated methodology for detecting, segmenting and classifying breast masses from mammograms with minimal user intervention. This is a long standing problem due to low signal-to-noise ratio in the visualisation of breast masses, combined with their large variability in terms of shape, size, appearance and location. We break the problem down into three stages: mass detection, mass segmentation, and mass classification. For the detection, we propose a cascade of deep learning methods to select hypotheses that are refined based on Bayesian optimisation. For the segmentation, we propose the use of deep structured output learning that is subsequently refined by a level set method. Finally, for the classification, we propose the use of a deep learning classifier, which is pre-trained with a regression to hand-crafted feature values and fine-tuned based on the annotations of the breast mass classification dataset. We test our proposed system on the publicly available INbreast dataset and compare the results with the current state-of-the-art methodologies. This evaluation shows that our system detects 90% of masses at 1 false positive per image, has a segmentation accuracy of around 0.85 (Dice index) on the correctly detected masses, and overall classifies masses as malignant or benign with sensitivity (Se) of 0.98 and specificity (Sp) of 0.7. Copyright © 2017 Elsevier B.V. All rights reserved.

  19. A population balance approach considering heat and mass transfer-Experiments and CFD simulations

    International Nuclear Information System (INIS)

    Krepper, Eckhard; Beyer, Matthias; Lucas, Dirk; Schmidtke, Martin

    2011-01-01

    Highlights: → The MUSIG approach was extended by mass transfer between the size groups to describe condensation or re-evaporation. → Experiments on steam bubble condensation in vertical co-current steam/water flows have been carried out. The cross sectional gas fraction distribution, the bubble size distribution ad the gas velocity profiles were measured. → The following phenomena could be reproduced with good agreement to the experiments: (a) Dependence of the condensation rate on the initial bubble size distribution and (b) re-evaporation over the height in tests with low inlet temperature subcooling. - Abstract: Bubble condensation in sub-cooled water is a complex process, to which various phenomena contribute. Since the condensation rate depends on the interfacial area density, bubble size distribution changes caused by breakup and coalescence play a crucial role. Experiments on steam bubble condensation in vertical co-current steam/water flows have been carried out in an 8 m long vertical DN200 pipe. Steam is injected into the pipe and the development of the bubbly flow is measured at different distances to the injection using a pair of wire mesh sensors. By varying the steam nozzle diameter the initial bubble size can be influenced. Larger bubbles come along with a lower interfacial area density and therefore condensate slower. Steam pressures between 1 and 6.5 MPa and sub-cooling temperatures from 2 to 12 K were applied. Due to the pressure drop along the pipe, the saturation temperature falls towards the upper pipe end. This affects the sub-cooling temperature and can even cause re-evaporation in the upper part of the test section. The experimental configurations are simulated with the CFD code CFX using an extended MUSIG approach, which includes the bubble shrinking or growth due to condensation or re-evaporation. The development of the vapour phase along the pipe with respect to vapour void fractions and bubble sizes is qualitatively well reproduced

  20. Bayesian approach to peak deconvolution and library search for high resolution gas chromatography - Mass spectrometry.

    Science.gov (United States)

    Barcaru, A; Mol, H G J; Tienstra, M; Vivó-Truyols, G

    2017-08-29

    A novel probabilistic Bayesian strategy is proposed to resolve highly coeluting peaks in high-resolution GC-MS (Orbitrap) data. Opposed to a deterministic approach, we propose to solve the problem probabilistically, using a complete pipeline. First, the retention time(s) for a (probabilistic) number of compounds for each mass channel are estimated. The statistical dependency between m/z channels was implied by including penalties in the model objective function. Second, Bayesian Information Criterion (BIC) is used as Occam's razor for the probabilistic assessment of the number of components. Third, a probabilistic set of resolved spectra, and their associated retention times are estimated. Finally, a probabilistic library search is proposed, computing the spectral match with a high resolution library. More specifically, a correlative measure was used that included the uncertainties in the least square fitting, as well as the probability for different proposals for the number of compounds in the mixture. The method was tested on simulated high resolution data, as well as on a set of pesticides injected in a GC-Orbitrap with high coelution. The proposed pipeline was able to detect accurately the retention times and the spectra of the peaks. For our case, with extremely high coelution situation, 5 out of the 7 existing compounds under the selected region of interest, were correctly assessed. Finally, the comparison with the classical methods of deconvolution (i.e., MCR and AMDIS) indicates a better performance of the proposed algorithm in terms of the number of correctly resolved compounds. Copyright © 2017 Elsevier B.V. All rights reserved.

  1. Assembly of a Vacuum Chamber: A Hands-On Approach to Introduce Mass Spectrometry

    Science.gov (United States)

    Bussie`re, Guillaume; Stoodley, Robin; Yajima, Kano; Bagai, Abhimanyu; Popowich, Aleksandra K.; Matthews, Nicholas E.

    2014-01-01

    Although vacuum technology is essential to many aspects of modern physical and analytical chemistry, vacuum experiments are rarely the focus of undergraduate laboratories. We describe an experiment that introduces students to vacuum science and mass spectrometry. The students first assemble a vacuum system, including a mass spectrometer. While…

  2. Total mass difference statistics algorithm: a new approach to identification of high-mass building blocks in electrospray ionization Fourier transform ion cyclotron mass spectrometry data of natural organic matter.

    Science.gov (United States)

    Kunenkov, Erast V; Kononikhin, Alexey S; Perminova, Irina V; Hertkorn, Norbert; Gaspar, Andras; Schmitt-Kopplin, Philippe; Popov, Igor A; Garmash, Andrew V; Nikolaev, Evgeniy N

    2009-12-15

    The ultrahigh-resolution Fourier transform ion cyclotron resonance (FTICR) mass spectrum of natural organic matter (NOM) contains several thousand peaks with dozens of molecules matching the same nominal mass. Such a complexity poses a significant challenge for automatic data interpretation, in which the most difficult task is molecular formula assignment, especially in the case of heavy and/or multielement ions. In this study, a new universal algorithm for automatic treatment of FTICR mass spectra of NOM and humic substances based on total mass difference statistics (TMDS) has been developed and implemented. The algorithm enables a blind search for unknown building blocks (instead of a priori known ones) by revealing repetitive patterns present in spectra. In this respect, it differs from all previously developed approaches. This algorithm was implemented in designing FIRAN-software for fully automated analysis of mass data with high peak density. The specific feature of FIRAN is its ability to assign formulas to heavy and/or multielement molecules using "virtual elements" approach. To verify the approach, it was used for processing mass spectra of sodium polystyrene sulfonate (PSS, M(w) = 2200 Da) and polymethacrylate (PMA, M(w) = 3290 Da) which produce heavy multielement and multiply-charged ions. Application of TMDS identified unambiguously monomers present in the polymers consistent with their structure: C(8)H(7)SO(3)Na for PSS and C(4)H(6)O(2) for PMA. It also allowed unambiguous formula assignment to all multiply-charged peaks including the heaviest peak in PMA spectrum at mass 4025.6625 with charge state 6- (mass bias -0.33 ppm). Application of the TMDS-algorithm to processing data on the Suwannee River FA has proven its unique capacities in analysis of spectra with high peak density: it has not only identified the known small building blocks in the structure of FA such as CH(2), H(2), C(2)H(2)O, O but the heavier unit at 154.027 amu. The latter was

  3. A dried blood spot mass spectrometry metabolomic approach for rapid breast cancer detection

    Directory of Open Access Journals (Sweden)

    Wang Q

    2016-03-01

    Full Text Available Qingjun Wang,1,2,* Tao Sun,3,* Yunfeng Cao,1,2,4,5 Peng Gao,2,4,6 Jun Dong,2,4 Yanhua Fang,2 Zhongze Fang,2 Xiaoyu Sun,2 Zhitu Zhu1,2 1Oncology Department 2, The First Affiliated Hospital of Liaoning Medical University, 2Personalized Treatment and Diagnosis Research Center, The First Affiliated Hospital of Liaoning Medical University and Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Jinzhou, 3Department of Internal Medicine 1, Cancer Hospital of China Medical University, Liaoning Cancer Hospital & Insititute, Shenyang, 4CAS Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, 5Key Laboratory of Contraceptives and Devices Research (NPFPC, Shanghai Engineer and Technology Research Center of Reproductive Health Drug and Devices, Shanghai Institute of Planned Parenthood Research, Shanghai, 6Clinical Laboratory, Dalian Sixth People’s Hospital, Dalian, People’s Republic of China *These authors contributed equally to this work Objective: Breast cancer (BC is still a lethal threat to women worldwide. An accurate screening and diagnosis strategy performed in an easy-to-operate manner is highly warranted in clinical perspective. Besides the routinely focused protein markers, blood is full of small molecular metabolites with diverse structures and properties. This study aimed to screen metabolite markers with BC diagnosis potentials.Methods: A dried blood spot-based direct infusion mass spectrometry (MS metabolomic analysis was conducted for BC and non-BC differentiation. The targeted analytes included 23 amino acids and 26 acylcarnitines.Results: Multivariate analysis screened out 21 BC-related metabolites in the blood. Regression analysis generated a diagnosis model consisting of parameters Pip, Asn, Pro, C14:1/C16, Phe/Tyr, and Gly/Ala. Tested with another set of BC and non-BC samples, this model showed a sensitivity of 92.2% and a specificity

  4. A Case Investigation of Product Structure Complexity in Mass Customization Using a Data Mining Approach

    DEFF Research Database (Denmark)

    Nielsen, Peter; Brunø, Thomas Ditlev; Nielsen, Kjeld

    2014-01-01

    This paper presents a data mining method for analyzing historical configuration data providing a number of opportunities for improving mass customization capabilities. The overall objective of this paper is to investigate how specific quantitative analyses, more specifically the association rule...

  5. Quantitation of multisite EGF receptor phosphorylation using mass spectrometry and a novel normalization approach

    DEFF Research Database (Denmark)

    Erba, Elisabetta Boeri; Matthiesen, Rune; Bunkenborg, Jakob

    2007-01-01

    Using stable isotope labeling and mass spectrometry, we performed a sensitive, quantitative analysis of multiple phosphorylation sites of the epidermal growth factor (EGF) receptor. Phosphopeptide detection efficiency was significantly improved by using the tyrosine phosphatase inhibitor sodium p...

  6. Mass Media and Religious Culture of the Audiences; Suggesting a Useful Approach to Media Productions for Children

    Directory of Open Access Journals (Sweden)

    Nasser Bahonar

    2008-10-01

    Full Text Available The religious program of mass media exclusively produced for children have had a significant growth in recent years. The artistic expression of stories related to the life of the great prophets and to the history of Islam as well as taking advantage of theatrical literature in religious occasions can herald successes in this neglected field. But, what is questionable in national religious policies in that why who are involved in the religious education of children whether in traditional media (family, mosques, religious communities, etc or in modern media (textbooks, press, radio and television do not follow an integrated and coherent policy based on a proved theoretical view of religious communications. In fact, this question results from the same old opposition between audience-oriented and media-oriented approaches in communications as well as the opposition between cognitivism and other approaches in psychology. The findings of the field of study conducted by the author along with psychological achievements of cognitivism in human communications and cultural audience-oriented approaches, especially reception theory in mass communications can solve some existing difficulties in the formulation of religious messages. Drawing upon the above mentioned theoretical schools, this article tries to introduce a useful approach to producing religious programs for children and describes the main tasks of mass media in this field accordingly.

  7. Demonstration of isotope-mass balance approach for water budget analyses of El-burulus Lake, Nile Delta, Egypt

    International Nuclear Information System (INIS)

    Sadek, M.A.

    2006-01-01

    The major elements of El-Burulus lake water system are rainfall, agricultural drainage discharge, groundwater, human activities, evaporation and water interaction between the lake and the Mediterranean sea. The principal input sources are agricultural drainage (8 drains at the southern borders of the lake), sea water as well as some contribution of precipitation, groundwater and human activities. Water is lost from the lake through evaporation and surface outflow. The present study has been conducted using isotopic / mass balance approach to investigate the water balance of El-Burulus lake and to emphasize the relative contribution of different input / output components which affect the environmental and hydrological terms of the system. An isotopic evaporation pan experiment was performed to estimate the parameters of relevance to water balance (isotopic composition of free air moisture and evaporating flux) and to simulate the isotopic enrichment of evaporation under atmospheric and hydraulic control. The isotopic mass balance approach employed herein facilitated the estimation of groundwater inflow to the lake, evaporated fraction of total lake inflow (E/I) and its fraction to outflow (E/O), ratio of surface inflow to surface outflow (I/O) as well as residence time of lake water. The isotopic mass balance approach has been validated by comparing the values of estimated parameters with the previous hydrological investigations; a quite good match has been indicated, the relevance of this approach is related to its integrative scale and the more simply implementation

  8. Mass transfer and slag-metal reaction in ladle refining : a CFD approach

    OpenAIRE

    Ramström, Eva

    2009-01-01

      In order to optimise the ladle treatment mass transfer modelling of aluminium addition and homogenisation time was carried out. It was stressed that incorporating slag-metal reactions into the mass transfer modelling strongly would enhance the reliability and amount of information to be analyzed from the CFD calculations.   In the present work, a thermodynamic model taking all the involved slag metal reactions into consideration was incorporated into a 2-D fluid flow model of an argon stirr...

  9. Approaches for the analysis of low molecular weight compounds with laser desorption/ionization techniques and mass spectrometry.

    Science.gov (United States)

    Bergman, Nina; Shevchenko, Denys; Bergquist, Jonas

    2014-01-01

    This review summarizes various approaches for the analysis of low molecular weight (LMW) compounds by different laser desorption/ionization mass spectrometry techniques (LDI-MS). It is common to use an agent to assist the ionization, and small molecules are normally difficult to analyze by, e.g., matrix assisted laser desorption/ionization mass spectrometry (MALDI-MS) using the common matrices available today, because the latter are generally small organic compounds themselves. This often results in severe suppression of analyte peaks, or interference of the matrix and analyte signals in the low mass region. However, intrinsic properties of several LDI techniques such as high sensitivity, low sample consumption, high tolerance towards salts and solid particles, and rapid analysis have stimulated scientists to develop methods to circumvent matrix-related issues in the analysis of LMW molecules. Recent developments within this field as well as historical considerations and future prospects are presented in this review.

  10. Slovenian National Landslide DataBase – A promising approach to slope mass movement prevention plan

    Directory of Open Access Journals (Sweden)

    Mihael Ribičič

    2007-12-01

    Full Text Available The Slovenian territory is, geologically speaking, very diverse and mainly composed of sediments or sedimentary rocks. Slope mass movements occur almost in all parts of the country. In the Alpine carbonate areas of the northern part of Slovenia rock falls, rock slides and even debris flows can be triggered.In the mountainous regions of central Slovenia composed from different clastic rocks, large soil landslides are quite usual, and in the young soil sediments of eastern part of Slovenia there is a large density of small soil landslides.The damage caused by slope mass movements is high, but still no common strategy and regulations to tackle this unwanted event, especially from the aspect of prevention, have been developed. One of the first steps towards an effective strategy of struggling against landslides and other slope mass movements is a central landslide database, where (ideally all known landslide occurrences would be reported, and described in as much detail as possible. At the end of the project of National Landslide Database construction which ended in May 2005 there were more than 6600 registered landslides, of which almost half occurred at a known location and were accompanied with the main characteristic descriptions.The erected database is a chance for Slovenia to once and for all start a solid slope mass movement prevention plan. The only part which is missing and which is the most important one is adopting a legal act that will legalise the obligation of reporting slope mass movement events to the database.

  11. New approach to 3-D, high sensitivity, high mass resolution space plasma composition measurements

    International Nuclear Information System (INIS)

    McComas, D.J.; Nordholt, J.E.

    1990-01-01

    This paper describes a new type of 3-D space plasma composition analyzer. The design combines high sensitivity, high mass resolution measurements with somewhat lower mass resolution but even higher sensitivity measurements in a single compact and robust design. While the lower resolution plasma measurements are achieved using conventional straight-through time-of-flight mass spectrometry, the high mass resolution measurements are made by timing ions reflected in a linear electric field (LEF), where the restoring force that an ion experiences is proportional to the depth it travels into the LEF region. Consequently, the ion's equation of motion in that dimension is that of a simple harmonic oscillator and its travel time is simply proportional to the square root of the ion's mass/charge (m/q). While in an ideal LEF, the m/q resolution can be arbitrarily high, in a real device the resolution is limited by the field linearity which can be achieved. In this paper we describe how a nearly linear field can be produced and discuss how the design can be optimized for various different plasma regimes and spacecraft configurations

  12. Comparison of a Mass Balance and an Ecosystem Model Approach when Evaluating the Carbon Cycling in a Lake Ecosystem

    International Nuclear Information System (INIS)

    Andersson, Eva; Sobek, Sebastian

    2006-01-01

    Carbon budgets are frequently used in order to understand the pathways of organic matter in ecosystems, and they also have an important function in the risk assessment of harmful substances. We compared two approaches, mass balance calculations and an ecosystem budget, to describe carbon processing in a shallow, oligotrophic hardwater lake. Both approaches come to the same main conclusion, namely that the lake is a net auto trophic ecosystem, in spite of its high dissolved organic carbon and low total phosphorus concentrations. However, there were several differences between the carbon budgets, e.g. in the rate of sedimentation and the air-water flux of CO 2 . The largest uncertainty in the mass balance is the contribution of emergent macrophytes to the carbon cycling of the lake, while the ecosystem budget is very sensitive towards the choice of conversion factors and literature values. While the mass balance calculations produced more robust results, the ecosystem budget gave valuable insights into the pathways of organic matter transfer in the ecosystem. We recommend that when using an ecosystem budget for the risk assessment of harmful substances, mass balance calculations should be performed in parallel in order to increase the robustness of the conclusions

  13. EXPOSURE TO MASS MEDIA AS A DOMINANT FACTOR INFLUENCING PUBLIC STIGMA TOWARD MENTAL ILLNESS BASED ON SUNRISE MODEL APPROACH

    Directory of Open Access Journals (Sweden)

    Ni Made Sintha Pratiwi

    2018-05-01

    Full Text Available Background: The person suffering mental disorders is not only burdened by his condition but also by the stigma. The impact of stigma extremely influences society that it is considered to be the obstacle in mental disorders therapy. Stigma as the society adverse view toward severe mental disorders is related with the cultural aspect. The interaction appeared from each component of nursing model namely sunrise model, which a model developed by Madeleine Leininger is connected with the wide society views about severe mental disorders condition in society. Objective: The aim of this study was to analyze the factors related to public stigma and to find out the dominant factors related to public stigma about severe mental illness through sunrise model approach in Sukonolo Village, Malang Regency. Methods: This study using observational analytical design with cross sectional approach. There were 150 respondents contributed in this study. The respondents were obtained using purposive sampling technique. Results: The results showed a significant relationship between mass media exposure, spiritual well-being, interpersonal contact, attitude, and knowledge with public stigma about mental illness. The result from multiple logistic regression shows the low exposure of mass media has the highest OR value at 26.744. Conclusion: There were significant correlation between mass media exposure, spiritual well-being, interpersonal contact, attitude, and knowledge with public stigma toward mental illness. Mass media exposure as a dominant factor influencing public stigma toward mental illness.

  14. A genome-wide approach accounting for body mass index identifies genetic variants influencing fasting glycemic traits and insulin resistance

    DEFF Research Database (Denmark)

    Manning, Alisa K; Hivert, Marie-France; Scott, Robert A

    2012-01-01

    pathways might be uncovered by accounting for differences in body mass index (BMI) and potential interactions between BMI and genetic variants. We applied a joint meta-analysis approach to test associations with fasting insulin and glucose on a genome-wide scale. We present six previously unknown loci...... associated with fasting insulin at P triglyceride and lower high-density lipoprotein (HDL) cholesterol levels, suggesting a role for these loci...

  15. Atomic spectrometry based on metallic tube atomizers heated by flame: Innovative strategies from fundamentals to analysis

    International Nuclear Information System (INIS)

    Arruda, Marco Aurelio Zezzi; Figueiredo, Eduardo Costa

    2009-01-01

    This review describes recent developments in atomic absorption spectrometry using metallic tube atomizers heated by flames. Sample introduction in spray or gaseous form is emphasized, describing some proposed systems for this task and the fundamentals involved in each context. The latest challenges and future possibilities for use of metallic tubes in atomic/mass spectrometry are also considered.

  16. Mass dispersions in a time-dependent mean-field approach

    International Nuclear Information System (INIS)

    Balian, R.; Bonche, P.; Flocard, H.; Veneroni, M.

    1984-05-01

    Characteristic functions for single-particle (s.p.) observables are evaluated by means of a time-dependent variational principle, which involves a state and an observable as conjugate variables. This provides a mean-field expression for fluctuations of s.p. observables, such as mass dispersions. The result differs from TDHF, it requires only the use of existing codes, and it presents attractive theoretical features. First numerical tests are encouraging. In particular, a calculation for 16 O + 16 O provides a significant increase of the predicted mass dispersion

  17. Reconnaissance Estimates of Recharge Based on an Elevation-dependent Chloride Mass-balance Approach

    Energy Technology Data Exchange (ETDEWEB)

    Charles E. Russell; Tim Minor

    2002-08-31

    Significant uncertainty is associated with efforts to quantity recharge in arid regions such as southern Nevada. However, accurate estimates of groundwater recharge are necessary to understanding the long-term sustainability of groundwater resources and predictions of groundwater flow rates and directions. Currently, the most widely accepted method for estimating recharge in southern Nevada is the Maxey and Eakin method. This method has been applied to most basins within Nevada and has been independently verified as a reconnaissance-level estimate of recharge through several studies. Recharge estimates derived from the Maxey and Eakin and other recharge methodologies ultimately based upon measures or estimates of groundwater discharge (outflow methods) should be augmented by a tracer-based aquifer-response method. The objective of this study was to improve an existing aquifer-response method that was based on the chloride mass-balance approach. Improvements were designed to incorporate spatial variability within recharge areas (rather than recharge as a lumped parameter), develop a more defendable lower limit of recharge, and differentiate local recharge from recharge emanating as interbasin flux. Seventeen springs, located in the Sheep Range, Spring Mountains, and on the Nevada Test Site were sampled during the course of this study and their discharge was measured. The chloride and bromide concentrations of the springs were determined. Discharge and chloride concentrations from these springs were compared to estimates provided by previously published reports. A literature search yielded previously published estimates of chloride flux to the land surface. {sup 36}Cl/Cl ratios and discharge rates of the three largest springs in the Amargosa Springs discharge area were compiled from various sources. This information was utilized to determine an effective chloride concentration for recharging precipitation and its associated uncertainty via Monte Carlo simulations

  18. Bilarge neutrino mixing and mass of the lightest neutrino from third generation dominance in a democratic approach

    International Nuclear Information System (INIS)

    Dermisek, Radovan

    2004-01-01

    We show that both small mixing in the quark sector and large mixing in the lepton sector can be obtained from a simple assumption of universality of Yukawa couplings and the right-handed neutrino Majorana mass matrix in leading order. We discuss conditions under which bilarge mixing in the lepton sector is achieved with a minimal amount of fine-tuning requirements for possible models. From knowledge of the solar and atmospheric mixing angles we determine the allowed values of sin θ 13 . If embedded into grand unified theories, the third generation Yukawa coupling unification is a generic feature while masses of the first two generations of charged fermions depend on small perturbations. In the neutrino sector, the heavier two neutrinos are model dependent, while the mass of the lightest neutrino in this approach does not depend on perturbations in the leading order. The right-handed neutrino mass scale can be identified with the GUT scale in which case the mass of the lightest neutrino is given as (m top 2 /M GUT )sin 2 θ 23 sin 2 θ 12 in the limit sin θ 13 ≅0. Discussing symmetries we make a connection with hierarchical models and show that the basis independent characteristic of this scenario is a strong dominance of the third generation right-handed neutrino, M 1 ,M 2 -4 M 3 , M 3 =M GUT

  19. Statistically optimal estimation of Greenland Ice Sheet mass variations from GRACE monthly solutions using an improved mascon approach

    Science.gov (United States)

    Ran, J.; Ditmar, P.; Klees, R.; Farahani, H. H.

    2018-03-01

    We present an improved mascon approach to transform monthly spherical harmonic solutions based on GRACE satellite data into mass anomaly estimates in Greenland. The GRACE-based spherical harmonic coefficients are used to synthesize gravity anomalies at satellite altitude, which are then inverted into mass anomalies per mascon. The limited spectral content of the gravity anomalies is properly accounted for by applying a low-pass filter as part of the inversion procedure to make the functional model spectrally consistent with the data. The full error covariance matrices of the monthly GRACE solutions are properly propagated using the law of covariance propagation. Using numerical experiments, we demonstrate the importance of a proper data weighting and of the spectral consistency between functional model and data. The developed methodology is applied to process real GRACE level-2 data (CSR RL05). The obtained mass anomaly estimates are integrated over five drainage systems, as well as over entire Greenland. We find that the statistically optimal data weighting reduces random noise by 35-69%, depending on the drainage system. The obtained mass anomaly time-series are de-trended to eliminate the contribution of ice discharge and are compared with de-trended surface mass balance (SMB) time-series computed with the Regional Atmospheric Climate Model (RACMO 2.3). We show that when using a statistically optimal data weighting in GRACE data processing, the discrepancies between GRACE-based estimates of SMB and modelled SMB are reduced by 24-47%.

  20. X-ray fluorescence spectrometry-based approach to precision management of bioavailable phosphorus in soil environments

    Science.gov (United States)

    Declining nutrient use efficiency in crop production has been a global priority to preserve high agricultural productivity with finite non-renewable nutrient resources, in particular phosphorus (P). Rapid spectroscopic methods increase measurement density of soil nutrients, and the availability of ...

  1. 20180318 - Structure identification by Mass Spectrometry Non-Targeted Analysis using the US EPA’s CompTox Chemistry Dashboard (ACS Spring)

    Science.gov (United States)

    Identification of unknowns in mass spectrometry based non-targeted analyses (NTA) requires the integration of complementary pieces of data to arrive at a confident, consensus structure. Researchers use chemical reference databases, spectral matching, fragment prediction tools, r...

  2. Data on coffee composition and mass spectrometry analysis of mixtures of coffee related carbohydrates, phenolic compounds and peptides

    Directory of Open Access Journals (Sweden)

    Ana S.P. Moreira

    2017-08-01

    Full Text Available The data presented here are related to the research paper entitled “Transglycosylation reactions, a main mechanism of phenolics incorporation in coffee melanoidins: inhibition by Maillard reaction” (Moreira et al., 2017 [1]. Methanolysis was applied in coffee fractions to quantify glycosidically-linked phenolics in melanoidins. Moreover, model mixtures mimicking coffee beans composition were roasted and analyzed using mass spectrometry-based approaches to disclose the regulatory role of proteins in transglycosylation reactions extension. This article reports the detailed chemical composition of coffee beans and derived fractions. In addition, it provides gas chromatography–mass spectrometry (GC–MS chromatograms and respective GC–MS spectra of silylated methanolysis products obtained from phenolic compounds standards, as well as the detailed identification of all compounds observed by electrospray mass spectrometry (ESI-MS analysis of roasted model mixtures, paving the way for the identification of the same type of compounds in other samples.

  3. The mass transfer approach to multivariate discrete first order stochastic dominance

    DEFF Research Database (Denmark)

    Østerdal, Lars Peter Raahave

    2010-01-01

    A fundamental result in the theory of stochastic dominance tells that first order dominance between two finite multivariate distributions is equivalent to the property that the one can be obtained from the other by shifting probability mass from one outcome to another that is worse a finite numbe...

  4. Novel approach to determine ghrelin analogs by liquid chromatography with mass spectrometry using a monolithic column

    Czech Academy of Sciences Publication Activity Database

    Zemenová, Jana; Sýkora, D.; Adámková, H.; Maletínská, Lenka; Elbert, Tomáš; Marek, Aleš; Blechová, Miroslava

    2017-01-01

    Roč. 40, č. 5 (2017), s. 1032-1039 ISSN 1615-9306 Institutional support: RVO:61388963 Keywords : enzyme-linked immunosorbent assay * ghrelin * lipopeptides * liquid chromatography mass spectrometry * monolithic columns Subject RIV: CB - Analytical Chemistry, Separation OBOR OECD: Analytical chemistry Impact factor: 2.557, year: 2016

  5. Integrated genomic approaches implicate osteoglycin (Ogn) in the regulation of left ventricular mass

    NARCIS (Netherlands)

    Petretto, Enrico; Sarwar, Rizwan; Grieve, Ian; Lu, Han; Kumaran, Mande K.; Muckett, Phillip J.; Mangion, Jonathan; Schroen, Blanche; Benson, Matthew; Punjabi, Prakash P.; Prasad, Sanjay K.; Pennell, Dudley J.; Kiesewetter, Chris; Tasheva, Elena S.; Corpuz, Lolita M.; Webb, Megan D.; Conrad, Gary W.; Kurtz, Theodore W.; Kren, Vladimir; Fischer, Judith; Hubner, Norbert; Pinto, Yigal M.; Pravenec, Michal; Aitman, Timothy J.; Cook, Stuart A.

    2008-01-01

    Left ventricular mass (LVM) and cardiac gene expression are complex traits regulated by factors both intrinsic and extrinsic to the heart. To dissect the major determinants of LVM, we combined expression quantitative trait locus1 and quantitative trait transcript (QTT) analyses of the cardiac

  6. Constraint specification in architecture : a user-oriented approach for mass customization

    NARCIS (Netherlands)

    Niemeijer, R.A.

    2011-01-01

    The last several decades, particularly those after the end of World War II, have seen an increasing industrialization of the housing industry. This was partially driven by the large demand for new houses that resulted from the baby boom and the destruction caused by the war. By adopting mass

  7. Sample collection and preparation of biofluids and extracts for gas chromatography-mass spectrometry.

    Science.gov (United States)

    Emwas, Abdul-Hamid M; Al-Talla, Zeyad A; Kharbatia, Najeh M

    2015-01-01

    To maximize the utility of gas chromatography-mass spectrometry (GC-MS) in metabonomics research, all stages of the experimental design should be standardized, including sample collection, storage, preparation, and sample separation. Moreover, the prerequisite for any GC-MS analysis is that a compound must be volatile and thermally stable if it is to be analyzed using this technique. Since many metabolites are nonvolatile and polar in nature, they are not readily amenable to analysis by GC-MS and require initial chemical derivatization of the polar functional groups in order to reduce the polarity and to increase the thermal stability and volatility of the analytes. In this chapter, an overview is presented of the optimum approach to sample collection, storage, and preparation for gas chromatography-mass spectrometry-based metabonomics with particular focus on urine samples as example of biofluids.

  8. Re-assessing Present Day Global Mass Transport and Glacial Isostatic Adjustment From a Data Driven Approach

    Science.gov (United States)

    Wu, X.; Jiang, Y.; Simonsen, S.; van den Broeke, M. R.; Ligtenberg, S.; Kuipers Munneke, P.; van der Wal, W.; Vermeersen, B. L. A.

    2017-12-01

    Determining present-day mass transport (PDMT) is complicated by the fact that most observations contain signals from both present day ice melting and Glacial Isostatic Adjustment (GIA). Despite decades of progress in geodynamic modeling and new observations, significant uncertainties remain in both. The key to separate present-day ice mass change and signals from GIA is to include data of different physical characteristics. We designed an approach to separate PDMT and GIA signatures by estimating them simultaneously using globally distributed interdisciplinary data with distinct physical information and a dynamically constructed a priori GIA model. We conducted a high-resolution global reappraisal of present-day ice mass balance with focus on Earth's polar regions and its contribution to global sea-level rise using a combination of ICESat, GRACE gravity, surface geodetic velocity data, and an ocean bottom pressure model. Adding ice altimetry supplies critically needed dual data types over the interiors of ice covered regions to enhance separation of PDMT and GIA signatures, and achieve half an order of magnitude expected higher accuracies for GIA and consequently ice mass balance estimates. The global data based approach can adequately address issues of PDMT and GIA induced geocenter motion and long-wavelength signatures important for large areas such as Antarctica and global mean sea level. In conjunction with the dense altimetry data, we solved for PDMT coefficients up to degree and order 180 by using a higher-resolution GRACE data set, and a high-resolution a priori PDMT model that includes detailed geographic boundaries. The high-resolution approach solves the problem of multiple resolutions in various data types, greatly reduces aliased errors from a low-degree truncation, and at the same time, enhances separation of signatures from adjacent regions such as Greenland and Canadian Arctic territories.

  9. Approach for domestic preparation of standard material (LSD spike) for isotope dilution mass spectrometry

    International Nuclear Information System (INIS)

    Ishikawa, Fumitaka; Sumi, Mika; Chiba, Masahiko; Suzuki, Toru; Abe, Tomoyuki; Kuno, Yusuke

    2008-01-01

    The accountancy analysis of the nuclear fuel material at Plutonium Fuel Development Center of JAEA is performed by isotope dilution mass spectrometry (IDMS; Isotope Dilution Mass Spectrometry). IDMS requires the standard material called LSD spike (Large Size Dried spike) which is indispensable for the accountancy in the facilities where the nuclear fuel materials are handled. Although the LSD spike and Pu source material have been supplied from foreign countries, the transportation for such materials has been getting more difficult recently. This difficulty may affect the operation of nuclear facilities in the future. Therefore, research and development of the domestic LSD spike and base material has been performed at JAEA. Certification for such standard nuclear materials including spikes produced in Japan is being studied. This report presents the current status and the future plan for the technological development. (author)

  10. Real estate market and building energy performance: Data for a mass appraisal approach.

    Science.gov (United States)

    Bonifaci, Pietro; Copiello, Sergio

    2015-12-01

    Mass appraisal is widely considered an advanced frontier in the real estate valuation field. Performing mass appraisal entails the need to get access to base information conveyed by a large amount of transactions, such as prices and property features. Due to the lack of transparency of many Italian real estate market segments, our survey has been addressed to gather data from residential property advertisements. The dataset specifically focuses on property offer prices and dwelling energy efficiency. The latter refers to the label expressed and exhibited by the energy performance certificate. Moreover, data are georeferenced with the highest possible accuracy: at the neighborhood level for a 76.8% of cases, at street or building number level for the remaining 23.2%. Data are related to the analysis performed in Bonifaci and Copiello [1], about the relationship between house prices and building energy performance, that is to say, the willingness to pay in order to benefit from more efficient dwellings.

  11. Westgate Shootings: An Emergency Department Approach to a Mass-casualty Incident.

    Science.gov (United States)

    Wachira, Benjamin W; Abdalla, Ramadhani O; Wallis, Lee A

    2014-10-01

    At approximately 12:30 pm on Saturday September 21, 2013, armed assailants attacked the upscale Westgate shopping mall in the Westlands area of Nairobi, Kenya. Using the seven key Major Incident Medical Management and Support (MIMMS) principles, command, safety, communication, assessment, triage, treatment, and transport, the Aga Khan University Hospital, Nairobi (AKUH,N) emergency department (ED) successfully coordinated the reception and care of all the casualties brought to the hospital. This report describes the AKUH,N ED response to the first civilian mass-casualty shooting incident in Kenya, with the hope of informing the development and implementation of mass-casualty emergency preparedness plans by other EDs and hospitals in Kenya, appropriate for the local health care system.

  12. Mathematical modelling of the mass-spring-damper system - A fractional calculus approach

    Directory of Open Access Journals (Sweden)

    Jesus Bernal Alvarado

    2012-08-01

    Full Text Available In this paper the fractional differential equation for the mass-spring-damper system in terms of the fractional time derivatives of the Caputo type is considered. In order to be consistent with the physical equation, a new parameter is introduced. This parameter char­acterizes the existence of fractional components in the system. A relation between the fractional order time derivative and the new parameter is found. Different particular cases are analyzed

  13. Mass lesions in chronic pancreatitis: benign or malignant? An "evidence-based practice" approach.

    LENUS (Irish Health Repository)

    Gerstenmaier, Jan F

    2012-02-01

    The diagnosis of a pancreatic mass lesion in the presence of chronic pancreatitis can be extremely challenging. At the same time, a high level of certainty about the diagnosis is necessary for appropriate management planning. The aim of this study was to establish current best evidence about which imaging methods reliably differentiate a benign from a malignant lesion, and show how that evidence is best applied. A diagnostic algorithm based on Bayesian analysis is proposed.

  14. Trip time prediction in mass transit companies. A machine learning approach

    OpenAIRE

    João M. Moreira; Alípio Jorge; Jorge Freire de Sousa; Carlos Soares

    2005-01-01

    In this paper we discuss how trip time prediction can be useful foroperational optimization in mass transit companies and which machine learningtechniques can be used to improve results. Firstly, we analyze which departmentsneed trip time prediction and when. Secondly, we review related work and thirdlywe present the analysis of trip time over a particular path. We proceed by presentingexperimental results conducted on real data with the forecasting techniques wefound most adequate, and concl...

  15. Mass Transfer and Chemical Reaction Approach of the Kinetics of the Acetylation of Gadung Flour using Glacial Acetic Acid

    Directory of Open Access Journals (Sweden)

    Andri Cahyo Kumoro

    2015-03-01

    Full Text Available Acetylation is one of the common methods of modifying starch properties by introducing acetil (CH3CO groups to starch molecules at low temperatures. While most acetylation is conducted using starch as anhidroglucose source and acetic anhydride or vinyl acetate as nucleophilic agents, this work employ reactants, namely flour and glacial acetic acid. The purpose of this work are to study the effect of pH reaction and GAA/GF mass ratio on the rate of acetylation reaction and to determine its rate constants. The acetylation of gadung flour with glacial acetic acid in the presence of sodium hydroxide as a homogenous catalyst was studied at ambient temperature with pH ranging from 8-10 and different mass ratio of acetic acid : gadung flour (1:3; 1:4; and 1:5. It was found that increasing pH, lead to increase the degree of substitution, while increasing GAA/GF mass ratio caused such decreases in the degree of substitution, due to the hydrolysis of the acetylated starch. The desired starch acetylation reaction is accompanied by undesirable hydrolysis reaction of the acetylated starch after 40-50 minutes reaction time. Investigation of kinetics of the reaction observed that the value of mass transfer rate constant (Kcs is smaller than the surface reaction rate constant (k. Thus, it can be concluded that rate controlling step is mass transfer.  © 2015 BCREC UNDIP. All rights reservedReceived: 7th August 2014; Revised: 8th September 2014; Accepted: 14th September 2014How to Cite: Kumoro, A.C., Amelia, R. (2015. Mass Transfer and Chemical Reaction Approach of the Kinetics of the Acetylation of Gadung Flour using Glacial Acetic Acid. Bulletin of Chemical Reaction Engineering & Catalysis, 10 (1: 30-37. (doi:10.9767/bcrec.10.1.7181.30-37Permalink/DOI: http://dx.doi.org/10.9767/bcrec.10.1.7181.30-37

  16. Windbreak effect on biomass and grain mass accumulation of corn: a modeling approach

    International Nuclear Information System (INIS)

    Zhang, H.; Brandle, J.R.

    1996-01-01

    While numerous studies have indicated that field windbreaks both improve crop growing conditions and generally enhance crop growth and yield, especially under less favorable conditions, the relationship between the two is not clearly understood. A simple model is proposed to simulate biomass and grain mass accumulation of corn (Zea mays L,) with a windbreak shelter or without (exposed condition). The model is based on the positive relationship between intercepted solar radiation and biomass accumulation and requires plant population and hourly inputs of solar radiation and air temperature. Using published data, radiation use efficiency (RUE) was related to plant population, and a temperature function was established between the relative corn growth and temperature for pre-silking stages. Biomass and grain mass simulated by the model agreed well with those measured for both sheltered and unsheltered plants from 1990 to 1992. Windbreaks did not significantly increase biomass or grain mass of corn for this study, even though air temperature was greater with than without shelter, probably indicating that the microclimatic changes induced by windbreaks were not physiologically significant for the 3-yr period studied. The model has potential use in future studies to relate windbreak effects to crop yield and to evaluate windbreak designs for maximum benefits

  17. The Impact of Microstructure Geometry on the Mass Transport in Artificial Pores: A Numerical Approach

    Directory of Open Access Journals (Sweden)

    Matthias Galinsky

    2014-01-01

    Full Text Available The microstructure of porous materials used in heterogeneous catalysis determines the mass transport inside networks, which may vary over many length scales. The theoretical prediction of mass transport phenomena in porous materials, however, is incomplete and is still not completely understood. Therefore, experimental data for every specific porous system is needed. One possible experimental technique for characterizing the mass transport in such pore networks is pulse experiments. The general evaluation of experimental outcomes of these techniques follows the solution of Fick’s second law where an integral and effective diffusion coefficient is recognized. However, a detailed local understanding of diffusion and sorption processes remains a challenge. As there is lack of proved models covering different length scales, existing classical concepts need to be evaluated with respect to their ability to reflect local geometries on the nanometer level. In this study, DSMC (Direct Simulation Monte Carlo models were used to investigate the impact of pore microstructures on the diffusion behaviour of gases. It can be understood as a virtual pulse experiment within a single pore or a combination of different pore geometries.

  18. A dynamical approach in exploring the unknown mass in the Solar system using pulsar timing arrays

    Science.gov (United States)

    Guo, Y. J.; Lee, K. J.; Caballero, R. N.

    2018-04-01

    The error in the Solar system ephemeris will lead to dipolar correlations in the residuals of pulsar timing array for widely separated pulsars. In this paper, we utilize such correlated signals, and construct a Bayesian data-analysis framework to detect the unknown mass in the Solar system and to measure the orbital parameters. The algorithm is designed to calculate the waveform of the induced pulsar-timing residuals due to the unmodelled objects following the Keplerian orbits in the Solar system. The algorithm incorporates a Bayesian-analysis suit used to simultaneously analyse the pulsar-timing data of multiple pulsars to search for coherent waveforms, evaluate the detection significance of unknown objects, and to measure their parameters. When the object is not detectable, our algorithm can be used to place upper limits on the mass. The algorithm is verified using simulated data sets, and cross-checked with analytical calculations. We also investigate the capability of future pulsar-timing-array experiments in detecting the unknown objects. We expect that the future pulsar-timing data can limit the unknown massive objects in the Solar system to be lighter than 10-11-10-12 M⊙, or measure the mass of Jovian system to a fractional precision of 10-8-10-9.

  19. Comparative Analysis of Mass Spectral Similarity Measures on Peak Alignment for Comprehensive Two-Dimensional Gas Chromatography Mass Spectrometry

    Science.gov (United States)

    2013-01-01

    Peak alignment is a critical procedure in mass spectrometry-based biomarker discovery in metabolomics. One of peak alignment approaches to comprehensive two-dimensional gas chromatography mass spectrometry (GC×GC-MS) data is peak matching-based alignment. A key to the peak matching-based alignment is the calculation of mass spectral similarity scores. Various mass spectral similarity measures have been developed mainly for compound identification, but the effect of these spectral similarity measures on the performance of peak matching-based alignment still remains unknown. Therefore, we selected five mass spectral similarity measures, cosine correlation, Pearson's correlation, Spearman's correlation, partial correlation, and part correlation, and examined their effects on peak alignment using two sets of experimental GC×GC-MS data. The results show that the spectral similarity measure does not affect the alignment accuracy significantly in analysis of data from less complex samples, while the partial correlation performs much better than other spectral similarity measures when analyzing experimental data acquired from complex biological samples. PMID:24151524

  20. Interrogating the Venom of the Viperid Snake Sistrurus catenatus edwardsii by a Combined Approach of Electrospray and MALDI Mass Spectrometry.

    Directory of Open Access Journals (Sweden)

    Alex Chapeaurouge

    Full Text Available The complete sequence characterization of snake venom proteins by mass spectrometry is rather challenging due to the presence of multiple isoforms from different protein families. In the present study, we investigated the tryptic digest of the venom of the viperid snake Sistrurus catenatus edwardsii by a combined approach of liquid chromatography coupled to either electrospray (online or MALDI (offline mass spectrometry. These different ionization techniques proved to be complementary allowing the identification a great variety of isoforms of diverse snake venom protein families, as evidenced by the detection of the corresponding unique peptides. For example, ten out of eleven predicted isoforms of serine proteinases of the venom of S. c. edwardsii were distinguished using this approach. Moreover, snake venom protein families not encountered in a previous transcriptome study of the venom gland of this snake were identified. In essence, our results support the notion that complementary ionization techniques of mass spectrometry allow for the detection of even subtle sequence differences of snake venom proteins, which is fundamental for future structure-function relationship and possible drug design studies.

  1. Novel approaches in analysis of Fusarium mycotoxins in cereals employing ultra performance liquid chromatography coupled with high resolution mass spectrometry

    International Nuclear Information System (INIS)

    Zachariasova, M.; Lacina, O.; Malachova, A.; Kostelanska, M.; Poustka, J.; Godula, M.; Hajslova, J.

    2010-01-01

    Rapid, simple and cost-effective analytical methods with performance characteristics matching regulatory requirements are needed for effective control of occurrence of Fusarium toxins in cereals and cereal-based products to which they might be transferred during processing. Within this study, two alternative approaches enabling retrospective data analysis and identification of unknown signals in sample extracts have been implemented and validated for determination of 11 major Fusarium toxins. In both cases, ultra-high performance liquid chromatography (U-HPLC) coupled with high resolution mass spectrometry (HR MS) was employed. 13 C isotopically labeled surrogates as well as matrix-matched standards were employed for quantification. As far as time of flight mass analyzer (TOF-MS) was a detection tool, the use of modified QuEChERS (quick easy cheap effective rugged and safe) sample preparation procedure, widely employed in multi-pesticides residue analysis, was shown as an optimal approach to obtain low detection limits. The second challenging alternative, enabling direct analysis of crude extract, was the use of mass analyzer based on Orbitrap technology. In addition to demonstration of full compliance of the new methods with Commission Regulation (EC) No. 401/2006, also their potential to be used for confirmatory purposes according to Commission Decision 2002/657/EC has been critically assessed.

  2. Mass spectrometry for biomarker development

    Energy Technology Data Exchange (ETDEWEB)

    Wu, Chaochao; Liu, Tao; Baker, Erin Shammel; Rodland, Karin D.; Smith, Richard D.

    2015-06-19

    Biomarkers potentially play a crucial role in early disease diagnosis, prognosis and targeted therapy. In the past decade, mass spectrometry based proteomics has become increasingly important in biomarker development due to large advances in technology and associated methods. This chapter mainly focuses on the application of broad (e.g. shotgun) proteomics in biomarker discovery and the utility of targeted proteomics in biomarker verification and validation. A range of mass spectrometry methodologies are discussed emphasizing their efficacy in the different stages in biomarker development, with a particular emphasis on blood biomarker development.

  3. Combining genomic and proteomic approaches for epigenetics research

    Science.gov (United States)

    Han, Yumiao; Garcia, Benjamin A

    2014-01-01

    Epigenetics is the study of changes in gene expression or cellular phenotype that do not change the DNA sequence. In this review, current methods, both genomic and proteomic, associated with epigenetics research are discussed. Among them, chromatin immunoprecipitation (ChIP) followed by sequencing and other ChIP-based techniques are powerful techniques for genome-wide profiling of DNA-binding proteins, histone post-translational modifications or nucleosome positions. However, mass spectrometry-based proteomics is increasingly being used in functional biological studies and has proved to be an indispensable tool to characterize histone modifications, as well as DNA–protein and protein–protein interactions. With the development of genomic and proteomic approaches, combination of ChIP and mass spectrometry has the potential to expand our knowledge of epigenetics research to a higher level. PMID:23895656

  4. A novel approach to finely tuned supersymmetric standard models: The case of the non-universal Higgs mass model

    Science.gov (United States)

    Yamaguchi, Masahiro; Yin, Wen

    2018-02-01

    Discarding the prejudice about fine tuning, we propose a novel and efficient approach to identify relevant regions of fundamental parameter space in supersymmetric models with some amount of fine tuning. The essential idea is the mapping of experimental constraints at a low-energy scale, rather than the parameter sets, to those of the fundamental parameter space. Applying this method to the non-universal Higgs mass model, we identify a new interesting superparticle mass pattern where some of the first two generation squarks are light whilst the stops are kept heavy as 6 TeV. Furthermore, as another application of this method, we show that the discrepancy of the muon anomalous magnetic dipole moment can be filled by a supersymmetric contribution within the 1{σ} level of the experimental and theoretical errors, which was overlooked by previous studies due to the extremely fine tuning required.

  5. An Artificial Gravity Spacecraft Approach which Minimizes Mass, Fuel and Orbital Assembly Reg

    Science.gov (United States)

    Bell, L.

    2002-01-01

    The Sasakawa International Center for Space Architecture (SICSA) is undertaking a multi-year research and design study that is exploring near and long-term commercial space development opportunities. Space tourism in low-Earth orbit (LEO), and possibly beyond LEO, comprises one business element of this plan. Supported by a financial gift from the owner of a national U.S. hotel chain, SICSA has examined opportunities, requirements and facility concepts to accommodate up to 100 private citizens and crewmembers in LEO, as well as on lunar/planetary rendezvous voyages. SICSA's artificial gravity Science Excursion Vehicle ("AGSEV") design which is featured in this presentation was conceived as an option for consideration to enable round-trip travel to Moon and Mars orbits and back from LEO. During the course of its development, the AGSEV would also serve other important purposes. An early assembly stage would provide an orbital science and technology testbed for artificial gravity demonstration experiments. An ultimate mature stage application would carry crews of up to 12 people on Mars rendezvous missions, consuming approximately the same propellant mass required for lunar excursions. Since artificial gravity spacecraft that rotate to create centripetal accelerations must have long spin radii to limit adverse effects of Coriolis forces upon inhabitants, SICSA's AGSEV design embodies a unique tethered body concept which is highly efficient in terms of structural mass and on-orbit assembly requirements. The design also incorporates "inflatable" as well as "hard" habitat modules to optimize internal volume/mass relationships. Other important considerations and features include: maximizing safety through element and system redundancy; means to avoid destabilizing mass imbalances throughout all construction and operational stages; optimizing ease of on-orbit servicing between missions; and maximizing comfort and performance through careful attention to human needs. A

  6. A simple theoretical approach to determine relative ion yield (RIY) in glow discharge mass spectrometry (GDMS)

    Energy Technology Data Exchange (ETDEWEB)

    Born, Sabine [Degussa AG, Hanau (Germany); Matsunami, Noriaki [Nagoya Univ. (Japan). Faculty of Engineering; Tawara, Hiroyuki [National Inst. for Fusion Science, Toki, Gifu (Japan)

    2000-01-01

    Direct current glow discharge mass spectrometry (dc-GDMS) has been applied to detect impurities in metals. The aim of this study is to understand quantitatively the processes taking place in GDMS and establish a model to calculate the relative ion yield (RIY), which is inversely proportional to the relative sensitivity factor (RSF), in order to achieve better agreement between the calculated and the experimental RIYs. A comparison is made between the calculated RIY of the present model and the experimental RIY, and also with other models. (author)

  7. A perturbative approach to mass-generation - the non-linear sigma model

    International Nuclear Information System (INIS)

    Davis, A.C.; Nahm, W.

    1985-01-01

    A calculational scheme is presented to include non-perturbative effects into the perturbation expansion. As an example we use the O(N + 1) sigma model. The scheme uses a natural parametrisation such that the lagrangian can be written in a form normal-ordered with respect to the O(N + 1) symmetric vacuum plus vacuum expectation values, the latter calculated by symmetry alone. Including such expectation values automatically leads to the inclusion of a mass-gap in the perturbation series. (orig.)

  8. Symplectic no-core shell-model approach to intermediate-mass nuclei

    Science.gov (United States)

    Tobin, G. K.; Ferriss, M. C.; Launey, K. D.; Dytrych, T.; Draayer, J. P.; Dreyfuss, A. C.; Bahri, C.

    2014-03-01

    We present a microscopic description of nuclei in the intermediate-mass region, including the proximity to the proton drip line, based on a no-core shell model with a schematic many-nucleon long-range interaction with no parameter adjustments. The outcome confirms the essential role played by the symplectic symmetry to inform the interaction and the winnowing of shell-model spaces. We show that it is imperative that model spaces be expanded well beyond the current limits up through 15 major shells to accommodate particle excitations, which appear critical to highly deformed spatial structures and the convergence of associated observables.

  9. Modeling the effect of levothyroxine therapy on bone mass density in postmenopausal women: a different approach leads to new inference

    Directory of Open Access Journals (Sweden)

    Tavangar Seyed

    2007-06-01

    Full Text Available Abstract Background The diagnosis, treatment and prevention of osteoporosis is a national health emergency. Osteoporosis quietly progresses without symptoms until late stage complications occur. Older patients are more commonly at risk of fractures due to osteoporosis. The fracture risk increases when suppressive doses of levothyroxine are administered especially in postmenopausal women. The question is; "When should bone mass density be tested in postmenopausal women after the initiation of suppressive levothyroxine therapy?". Standard guidelines for the prevention of osteoporosis suggest that follow-up be done in 1 to 2 years. We were interested in predicting the level of bone mass density in postmenopausal women after the initiation of suppressive levothyroxine therapy with a novel approach. Methods The study used data from the literature on the influence of exogenous thyroid hormones on bone mass density. Four cubic polynomial equations were obtained by curve fitting for Ward's triangle, trochanter, spine and femoral neck. The behaviors of the models were investigated by statistical and mathematical analyses. Results There are four points of inflexion on the graphs of the first derivatives of the equations with respect to time at about 6, 5, 7 and 5 months. In other words, there is a maximum speed of bone loss around the 6th month after the start of suppressive L-thyroxine therapy in post-menopausal women. Conclusion It seems reasonable to check bone mass density at the 6th month of therapy. More research is needed to explain the cause and to confirm the clinical application of this phenomenon for osteoporosis, but such an approach can be used as a guide to future experimentation. The investigation of change over time may lead to more sophisticated decision making in a wide variety of clinical problems.

  10. Derivation of mass relations for composite W* and Z* from effective Lagrangian approach

    International Nuclear Information System (INIS)

    Yasue, Masaki; Oneda, Sadao.

    1985-04-01

    In an effective-Lagrangian model with gauge bosons (W,Z,γ) and their neighboring spin J=1 composites (W*,Z*), we find relations among their masses, m sub(W), m sub(Z), m sub(W*) and m sub(Z*): m sub(W) m sub(W*) = cos theta m sub(Z) m sub(Z*) (as a generalization of m sub(W) = cos theta m sub(Z)) and m sub(W) 2 + m sub(W*) 2 + tan 2 theta m sub(W0) 2 = m sub(Z) 2 + m sub(Z*) 2 with m sub(W0) being the mass of W in the standard model provided that the system respects the SU(2) sub(L) x U(1) sub(Y) symmetry. W* and Z* are taken as the lowest-lying excited states belonging to an SU(2) sub(L)-triplet in the symmetric limit. The existence of W* coupling to the V-A current modifies the relation between G sub(F) and M sub(W) and that of Z* generates a new interaction of the (Jsup(em)) 2 -type as well as the deviation of sin theta sub(W) observed at low energies from the mixing angle sin theta in neutral-current interactions. (author)

  11. New approach to the characterization of pyrolysis coal products by gas chromatography mass spectrometry

    Energy Technology Data Exchange (ETDEWEB)

    Cappiello, A.; Mangani, F.; Bruner, F.; Bonfanti, L. [University of Urbino, Urbino (Italy)

    1996-06-07

    A method for the characterization of coal thermal behaviour, based on gas chromatographic-mass spectrometric analysis of the pyrolysate, is presented. Twelve different coal samples representative of the entire coal rank, were selected. The pyrolysis products, obtained at 800{degree}C, were first collected and then analysed in two GC-MS systems. The sampling apparatus consisted of three different traps in order to separate the products into three fractions on the basis of their volatility. The GC-MS analysis was also arranged according to this criterion. A packed column, coupled to a double-focusing magnetic mass spectrometer, was used for the volatile fractions of the pyrolysate and a capillary column, coupled to a quadruple analyser, was employed for the analysis of the condensed fraction. Sampling and analysis procedures were carried out separately, thus allowing careful optimization of the strategy for the characterization of the pyrolysate. The condensate was analysed in the selected-ion monitoring mode for the determination of different classes of compounds. Some evaluations and comparisons, extrapolated from the results obtained, are presented.

  12. Mass Spectrometric Approaches to the Identification of Potential Ingredients in Cigarette Smoke Causing Cytotoxicity.

    Science.gov (United States)

    Horiyama, Shizuyo; Kunitomo, Masaru; Yoshikawa, Noriko; Nakamura, Kazuki

    2016-01-01

    Cigarette smoke contains many harmful chemicals that contribute to the pathogenesis of smoking-related diseases such as chronic obstructive pulmonary disease, cancer, and cardiovascular disease. Many studies have been done to identify cytotoxic chemicals in cigarette smoke and elucidate the onset of the above-mentioned diseases caused by smoking. However, definitive mechanisms for cigarette smoke toxicity remain unknown. As candidates for cytotoxic chemicals, we have recently found methyl vinyl ketone (MVK) and acetic anhydride in nicotine/tar-free cigarette smoke extract (CSE) using L-tyrosine (Tyr), an amino acid with highly reactive hydroxyl group. The presence of MVK and acetic anhydride in CSE was confirmed by gas chromatography-mass spectrometry (GC/MS). We also found new reaction products formed in B16-BL6 mouse melanoma (B16-BL6) cells treated with CSE using LC/MS. These were identified as glutathione (GSH) conjugates of α,β-unsaturated carbonyl compounds, MVK, crotonaldehyde (CA), and acrolein (ACR), by the mass value and product ion spectra of these new products. ACR and MVK are type-2 alkenes, which are well known as electron acceptors and form Michael-type adducts to nucleophilic side chain of amino acids on peptides. These α,β-unsaturated carbonyl compounds may have a key role in CSE-induced cell death.

  13. Estimating Regional Mass Balance of Himalayan Glaciers Using Hexagon Imagery: An Automated Approach

    Science.gov (United States)

    Maurer, J. M.; Rupper, S.

    2013-12-01

    Currently there is much uncertainty regarding the present and future state of Himalayan glaciers, which supply meltwater for river systems vital to more than 1.4 billion people living throughout Asia. Previous assessments of regional glacier mass balance in the Himalayas using various remote sensing and field-based methods give inconsistent results, and most assessments are over relatively short (e.g., single decade) timescales. This study aims to quantify multi-decadal changes in volume and extent of Himalayan glaciers through efficient use of the large database of declassified 1970-80s era Hexagon stereo imagery. Automation of the DEM extraction process provides an effective workflow for many images to be processed and glacier elevation changes quantified with minimal user input. The tedious procedure of manual ground control point selection necessary for block-bundle adjustment (as ephemeral data is not available for the declassified images) is automated using the Maximally Stable Extremal Regions algorithm, which matches image elements between raw Hexagon images and georeferenced Landsat 15 meter panchromatic images. Additional automated Hexagon DEM processing, co-registration, and bias correction allow for direct comparison with modern ASTER and SRTM elevation data, thus quantifying glacier elevation and area changes over several decades across largely inaccessible mountainous regions. As consistent methodology is used for all glaciers, results will likely reveal significant spatial and temporal patterns in regional ice mass balance. Ultimately, these findings could have important implications for future water resource management in light of environmental change.

  14. Bayesian approach to peak deconvolution and library search for high resolution gas chromatography - Mass spectrometry

    NARCIS (Netherlands)

    Barcaru, A.; Mol, H.G.J.; Tienstra, M.; Vivó-Truyols, G.

    2017-01-01

    A novel probabilistic Bayesian strategy is proposed to resolve highly coeluting peaks in high-resolution GC-MS (Orbitrap) data. Opposed to a deterministic approach, we propose to solve the problem probabilistically, using a complete pipeline. First, the retention time(s) for a (probabilistic) number

  15. Approaches towards the automated interpretation and prediction of electrospray tandem mass spectra of non-peptidic combinatorial compounds.

    Science.gov (United States)

    Klagkou, Katerina; Pullen, Frank; Harrison, Mark; Organ, Andy; Firth, Alistair; Langley, G John

    2003-01-01

    Combinatorial chemistry is widely used within the pharmaceutical industry as a means of rapid identification of potential drugs. With the growth of combinatorial libraries, mass spectrometry (MS) became the key analytical technique because of its speed of analysis, sensitivity, accuracy and ability to be coupled with other analytical techniques. In the majority of cases, electrospray mass spectrometry (ES-MS) has become the default ionisation technique. However, due to the absence of fragment ions in the resulting spectra, tandem mass spectrometry (MS/MS) is required to provide structural information for the identification of an unknown analyte. This work discusses the first steps of an investigation into the fragmentation pathways taking place in electrospray tandem mass spectrometry. The ultimate goal for this project is to set general fragmentation rules for non-peptidic, pharmaceutical, combinatorial compounds. As an aid, an artificial intelligence (AI) software package is used to facilitate interpretation of the spectra. This initial study has focused on determining the fragmentation rules for some classes of compound types that fit the remit as outlined above. Based on studies carried out on several combinatorial libraries of these compounds, it was established that different classes of drug molecules follow unique fragmentation pathways. In addition to these general observations, the specific ionisation processes and the fragmentation pathways involved in the electrospray mass spectra of these systems were explored. The ultimate goal will be to incorporate our findings into the computer program and allow identification of an unknown, non-peptidic compound following insertion of its ES-MS/MS spectrum into the AI package. The work herein demonstrates the potential benefit of such an approach in addressing the issue of high-throughput, automated MS/MS data interpretation. Copyright 2003 John Wiley & Sons, Ltd.

  16. Chromatographic, Spectroscopic and Mass Spectrometric Approaches for Exploring the Habitability of Mars in 2012 and Beyond with the Curiosity Rover

    Science.gov (United States)

    Mahaffy, Paul

    2012-01-01

    The Sample Analysis at Mars (SAM) suite of instruments on the Curiosity Rover of Mars Science Laboratory Mission is designed to provide chemical and isotopic analysis of organic and inorganic volatiles for both atmospheric and solid samples. The goals of the science investigation enabled by the gas chromatograph mass spectrometer and tunable laser spectrometer instruments of SAM are to work together with the other MSL investigations is to quantitatively assess habitability through a series of chemical and geological measurements. We describe the multi-column gas chromatograph system employed on SAM and the approach to extraction and analysis of organic compounds that might be preserved in ancient martian rocks.

  17. Tandem mass spectrometry: a convenient approach in the dosage of steviol glycosides in Stevia sweetened commercial food beverages.

    Science.gov (United States)

    Di Donna, L; Mazzotti, F; Santoro, I; Sindona, G

    2017-05-01

    The use of sweeteners extracted from leaves of the plant species Stevia rebaudiana is increasing worldwide. They are recognized as generally recognized as safe by the US-FDA and approved by EU-European Food Safety Authority, with some recommendation on the daily dosage that should not interfere with glucose metabolism. The results presented here introduce an easy analytical approach for the identification and assay of Stevia sweeteners in commercially available soft drink, based on liquid chromatography coupled to tandem mass spectrometry, using a natural statin-like molecule, Brutieridin, as internal standard. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

  18. Geochemical modelling of Na-SO4 type groundwater at Palmottu using a mass balance approach

    International Nuclear Information System (INIS)

    Pitkaenen, P.

    1993-01-01

    The mass balance chemical modelling technique has been applied to the groundwaters at the Palmottu analogue study site (in southwestern Finland) for radioactive waste disposal. The geochemical modelling concentrates on the evolution of Na-SO 4 type groundwater, which is spatially connected to the uranium mineralization. The results calculated along an assumed flow path are consistent with available field data and thermodynamic constraints. The results show that essential production of sulphides is unrealistic in the prevailing conditions. The increasing concentrations of Na, SO 4 and Cl along the evolution trend seem to have the same source and they could originate mainly from the leakage of fluid inclusions. Some mixing of relict sea water is also possible

  19. Global black p-brane world: a new approach to stable mass hierarchy

    International Nuclear Information System (INIS)

    Moon, Sei-Hoon; Rey, Soo-Jong; Kim, Yoonbai

    2001-01-01

    We find a class of extremal black hole-like global p-brane in higher-dimensional gravity with a negative cosmological constant. The region inside the p-brane horizon possesses all essential features required for the Randall-Sundrum type brane world scenario. The set-up allows to interpret the horizon size as the compactification size in that the Planck scale M Pl is determined by the fundamental scale M * and the horizon size r H via the familiar relation M Pl 2 ∼M * 2+n r H n , and the gravity behaves as expected in a world with n-extra dimensions compactified with size r H . Most importantly, a stable mass hierarchy between M Pl and M * can be generated from topological charge of the p-brane and the horizon size r H therein. We also offer a new perspective on various issues associated to the brane world scenarios including the cosmological constant problem

  20. Current mass spectrometry approaches and challenges for the bioanalysis of traditional Chinese medicines.

    Science.gov (United States)

    Dong, Xin; Wang, Rui; Zhou, Xu; Li, Ping; Yang, Hua

    2016-07-15

    Traditional Chinese medicines (TCMs) are gaining more and more attentions all over the world. The focus of TCMs researches were gradually shifted from chemical research to the combination study of chemical and life sciences. However, obtaining precise information of TCMs process in vivo or in vitro is still a bottleneck in bioanalysis of TCMs for their chemical composition complexity. This paper reviewed the recent analytical methods especially mass spectrometry technology in the bioanalysis of TCMs, and data processing techniques in the qualitative and quantitative analyses of metabolite of TCMs. Additionally, the difficulties encountered in the analyzing biological samples in TCMs and the solutions to these problems have been mentioned. Copyright © 2015 Elsevier B.V. All rights reserved.

  1. An Interprofessional Approach to Continuing Education With Mass Casualty Simulation: Planning and Execution.

    Science.gov (United States)

    Saber, Deborah A; Strout, Kelley; Caruso, Lisa Swanson; Ingwell-Spolan, Charlene; Koplovsky, Aiden

    2017-10-01

    Many natural and man-made disasters require the assistance from teams of health care professionals. Knowing that continuing education about disaster simulation training is essential to nursing students, nurses, and emergency first responders (e.g., emergency medical technicians, firefighters, police officers), a university in the northeastern United States planned and implemented an interprofessional mass casualty incident (MCI) disaster simulation using the Project Management Body of Knowledge (PMBOK) management framework. The school of nursing and University Volunteer Ambulance Corps (UVAC) worked together to simulate a bus crash with disaster victim actors to provide continued education for community first responders and train nursing students on the MCI process. This article explains the simulation activity, planning process, and achieved outcomes. J Contin Educ Nurs. 2017;48(10):447-453. Copyright 2017, SLACK Incorporated.

  2. Honeybee venom proteome profile of queens and winter bees as determined by a mass spectrometric approach.

    Science.gov (United States)

    Danneels, Ellen L; Van Vaerenbergh, Matthias; Debyser, Griet; Devreese, Bart; de Graaf, Dirk C

    2015-10-30

    Venoms of invertebrates contain an enormous diversity of proteins, peptides, and other classes of substances. Insect venoms are characterized by a large interspecific variation resulting in extended lists of venom compounds. The venom composition of several hymenopterans also shows different intraspecific variation. For instance, venom from different honeybee castes, more specifically queens and workers, shows quantitative and qualitative variation, while the environment, like seasonal changes, also proves to be an important factor. The present study aimed at an in-depth analysis of the intraspecific variation in the honeybee venom proteome. In summer workers, the recent list of venom proteins resulted from merging combinatorial peptide ligand library sample pretreatment and targeted tandem mass spectrometry realized with a Fourier transform ion cyclotron resonance mass spectrometer (FT-ICR MS/MS). Now, the same technique was used to determine the venom proteome of queens and winter bees, enabling us to compare it with that of summer bees. In total, 34 putative venom toxins were found, of which two were never described in honeybee venoms before. Venom from winter workers did not contain toxins that were not present in queens or summer workers, while winter worker venom lacked the allergen Api m 12, also known as vitellogenin. Venom from queen bees, on the other hand, was lacking six of the 34 venom toxins compared to worker bees, while it contained two new venom toxins, in particularly serine proteinase stubble and antithrombin-III. Although people are hardly stung by honeybees during winter or by queen bees, these newly identified toxins should be taken into account in the characterization of a putative allergic response against Apis mellifera stings.

  3. Honeybee Venom Proteome Profile of Queens and Winter Bees as Determined by a Mass Spectrometric Approach

    Science.gov (United States)

    Danneels, Ellen L.; Van Vaerenbergh, Matthias; Debyser, Griet; Devreese, Bart; de Graaf, Dirk C.

    2015-01-01

    Venoms of invertebrates contain an enormous diversity of proteins, peptides, and other classes of substances. Insect venoms are characterized by a large interspecific variation resulting in extended lists of venom compounds. The venom composition of several hymenopterans also shows different intraspecific variation. For instance, venom from different honeybee castes, more specifically queens and workers, shows quantitative and qualitative variation, while the environment, like seasonal changes, also proves to be an important factor. The present study aimed at an in-depth analysis of the intraspecific variation in the honeybee venom proteome. In summer workers, the recent list of venom proteins resulted from merging combinatorial peptide ligand library sample pretreatment and targeted tandem mass spectrometry realized with a Fourier transform ion cyclotron resonance mass spectrometer (FT-ICR MS/MS). Now, the same technique was used to determine the venom proteome of queens and winter bees, enabling us to compare it with that of summer bees. In total, 34 putative venom toxins were found, of which two were never described in honeybee venoms before. Venom from winter workers did not contain toxins that were not present in queens or summer workers, while winter worker venom lacked the allergen Api m 12, also known as vitellogenin. Venom from queen bees, on the other hand, was lacking six of the 34 venom toxins compared to worker bees, while it contained two new venom toxins, in particularly serine proteinase stubble and antithrombin-III. Although people are hardly stung by honeybees during winter or by queen bees, these newly identified toxins should be taken into account in the characterization of a putative allergic response against Apis mellifera stings. PMID:26529016

  4. Mass spectrometric approaches for the identification of anthracycline analogs produced by actinobacteria.

    Science.gov (United States)

    Bauermeister, Anelize; Zucchi, Tiago Domingues; Moraes, Luiz Alberto Beraldo

    2016-06-01

    Anthracyclines are a well-known chemical class produced by actinobacteria used effectively in cancer treatment; however, these compounds are usually produced in few amounts because of being toxic against their producers. In this work, we successfully explored the mass spectrometry versatility to detect 18 anthracyclines in microbial crude extract. From collision-induced dissociation and nuclear magnetic resonance spectra, we proposed structures for five new and identified three more anthracyclines already described in the literature, nocardicyclins A and B and nothramicin. One new compound 8 (4-[4-(dimethylamino)-5-hydroxy-4,6-dimethyloxan-2-yl]oxy-2,5,7,12-tetrahydroxy-3,10-dimethoxy-2-methyl-3,4-dihydrotetracene-1,6,11-trione) was isolated and had its structure confirmed by (1) H nuclear magnetic resonance. The anthracyclines identified in this work show an interesting aminoglycoside, poorly found in natural products, 3-methyl-rhodosamine and derivatives. This fact encouraged to develop a focused method to identify compounds with aminoglycosides (rhodosamine, m/z 158; 3-methyl-rhodosamine, m/z 172; 4'-O-acethyl-3-C-methyl-rhodosamine, m/z 214). This method allowed the detection of four more anthracyclines. This focused method can also be applied in the search of these aminoglycosides in other microbial crude extracts. Additionally, it was observed that nocardicyclin A, nothramicin and compound 8 were able to interact to DNA through a DNA-binding study by mass spectrometry, showing its potential as anticancer drugs. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  5. Quantifying non-linear dynamics of mass-springs in series oscillators via asymptotic approach

    Science.gov (United States)

    Starosta, Roman; Sypniewska-Kamińska, Grażyna; Awrejcewicz, Jan

    2017-05-01

    Dynamical regular response of an oscillator with two serially connected springs with nonlinear characteristics of cubic type and governed by a set of differential-algebraic equations (DAEs) is studied. The classical approach of the multiple scales method (MSM) in time domain has been employed and appropriately modified to solve the governing DAEs of two systems, i.e. with one- and two degrees-of-freedom. The approximate analytical solutions have been verified by numerical simulations.

  6. Challenging posterior mediastinal mass resection via a minimally invasive approach with neurological monitoring.

    Science.gov (United States)

    Smail, Hassiba; Baste, Jean Marc; Melki, Jean; Peillon, Christophe

    2013-02-01

    We report a novel surgical strategy for the resection of a rare type of posterior mediastinal tumour in a young patient. A melanotic schwannoma arose from the left thoracic sympathetic chain, adjacent to the origin of the artery of Adamkiewicz. Successful excision of this tumour via a minimally invasive approach without arterial or spinal cord injury was possible with the aid of neurological monitoring using spinal-evoked potentials.

  7. The influence of parent's body mass index on peer selection: an experimental approach using virtual reality.

    Science.gov (United States)

    Martarelli, Corinna S; Borter, Natalie; Bryjova, Jana; Mast, Fred W; Munsch, Simone

    2015-11-30

    Relatively little is known about the influence of psychosocial factors, such as familial role modeling and social network on the development and maintenance of childhood obesity. We investigated peer selection using an immersive virtual reality environment. In a virtual schoolyard, children were confronted with normal weight and overweight avatars either eating or playing. Fifty-seven children aged 7-13 participated. Interpersonal distance to the avatars, child's BMI, self-perception, eating behavior and parental BMI were assessed. Parental BMI was the strongest predictor for the children's minimal distance to the avatars. Specifically, a higher mothers' BMI was associated with greater interpersonal distance and children approached closer to overweight eating avatars. A higher father's BMI was associated with a lower interpersonal distance to the avatars. These children approached normal weight playing and overweight eating avatar peers closest. The importance of parental BMI for the child's social approach/avoidance behavior can be explained through social modeling mechanisms. Differential effects of paternal and maternal BMI might be due to gender specific beauty ideals. Interventions to promote social interaction with peer groups could foster weight stabilization or weight loss in children. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  8. Structural characterisation of medically relevant protein assemblies by integrating mass spectrometry with computational modelling.

    Science.gov (United States)

    Politis, Argyris; Schmidt, Carla

    2018-03-20

    Structural mass spectrometry with its various techniques is a powerful tool for the structural elucidation of medically relevant protein assemblies. It delivers information on the composition, stoichiometries, interactions and topologies of these assemblies. Most importantly it can deal with heterogeneous mixtures and assemblies which makes it universal among the conventional structural techniques. In this review we summarise recent advances and challenges in structural mass spectrometric techniques. We describe how the combination of the different mass spectrometry-based methods with computational strategies enable structural models at molecular levels of resolution. These models hold significant potential for helping us in characterizing the function of protein assemblies related to human health and disease. In this review we summarise the techniques of structural mass spectrometry often applied when studying protein-ligand complexes. We exemplify these techniques through recent examples from literature that helped in the understanding of medically relevant protein assemblies. We further provide a detailed introduction into various computational approaches that can be integrated with these mass spectrometric techniques. Last but not least we discuss case studies that integrated mass spectrometry and computational modelling approaches and yielded models of medically important protein assembly states such as fibrils and amyloids. Copyright © 2017 The Author(s). Published by Elsevier B.V. All rights reserved.

  9. Mass-spectrometric exploration of proteome structure and function

    DEFF Research Database (Denmark)

    Aebersold, Ruedi; Mann, Matthias

    2016-01-01

    , the structures and functions of selected proteins have been studied using biochemical and biophysical methods. However, the properties and behaviour of the proteome as an integrated system have largely remained elusive. Powerful mass-spectrometry-based technologies now provide unprecedented insights...

  10. Advances in characterizing ubiquitylation sites by mass spectrometry

    DEFF Research Database (Denmark)

    Sylvestersen, K.B.; Young, C.; Nielsen, M.L.

    2013-01-01

    of ubiquitylation is a two-fold challenge that involves the mapping of ubiquitylation sites and the determination of ubiquitin chain topology. This review focuses on the technical advances in the mass spectrometry-based characterization of ubiquitylation sites, which have recently involved the large...

  11. Automatic Compound Annotation from Mass Spectrometry Data Using MAGMa.

    NARCIS (Netherlands)

    Ridder, L.O.; Hooft, van der J.J.J.; Verhoeven, S.

    2014-01-01

    The MAGMa software for automatic annotation of mass spectrometry based fragmentation data was applied to 16 MS/MS datasets of the CASMI 2013 contest. Eight solutions were submitted in category 1 (molecular formula assignments) and twelve in category 2 (molecular structure assignment). The MS/MS

  12. Estimating the ice thickness of mountain glaciers with an inverse approach using surface topography and mass-balance

    International Nuclear Information System (INIS)

    Michel, Laurent; Picasso, Marco; Farinotti, Daniel; Bauder, Andreas; Funk, Martin; Blatter, Heinz

    2013-01-01

    We present a numerical method to estimate the ice thickness distribution within a two-dimensional, non-sliding mountain glacier, given a transient surface geometry and a mass-balance distribution, which are relatively easy to obtain for a large number of glaciers. The inverse approach is based on the shallow ice approximation (SIA) of ice flow and requires neither filtering of the surface topography with a lower slope limit nor approximation of constant basal shear stress. We first address this problem for a steady-state surface geometry. Next, we use an apparent surface mass-balance description that makes the transient evolution quasi-stationary. Then, we employ a more elaborated fixed-point method in which the bedrock solution is iteratively obtained by adding the difference between the computed and known surface geometries at the end of the considered time interval. In a sensitivity study, we show that the procedure is much more susceptible to small perturbations in surface geometry than mass-balance. Finally, we present preliminary results for bed elevations in three space dimensions. (paper)

  13. The mass-action law based algorithm for cost-effective approach for cancer drug discovery and development.

    Science.gov (United States)

    Chou, Ting-Chao

    2011-01-01

    The mass-action law based system analysis via mathematical induction and deduction lead to the generalized theory and algorithm that allows computerized simulation of dose-effect dynamics with small size experiments using a small number of data points in vitro, in animals, and in humans. The median-effect equation of the mass-action law deduced from over 300 mechanism specific-equations has been shown to be the unified theory that serves as the common-link for complicated biomedical systems. After using the median-effect principle as the common denominator, its applications are mechanism-independent, drug unit-independent, and dynamic order-independent; and can be used generally for single drug analysis or for multiple drug combinations in constant-ratio or non-constant ratios. Since the "median" is the common link and universal reference point in biological systems, these general enabling lead to computerized quantitative bio-informatics for econo-green bio-research in broad disciplines. Specific applications of the theory, especially relevant to drug discovery, drug combination, and clinical trials, have been cited or illustrated in terms of algorithms, experimental design and computerized simulation for data analysis. Lessons learned from cancer research during the past fifty years provide a valuable opportunity to reflect, and to improve the conventional divergent approach and to introduce a new convergent avenue, based on the mass-action law principle, for the efficient cancer drug discovery and the low-cost drug development.

  14. Body-mass or sex-biased tick parasitism in roe deer (Capreolus capreolus)? A GAMLSS approach.

    Science.gov (United States)

    Kiffner, C; Lödige, C; Alings, M; Vor, T; Rühe, F

    2011-03-01

    Macroparasites feeding on wildlife hosts follow skewed distributions for which basic statistical approaches are of limited use. To predict Ixodes spp. tick burden on roe deer, we applied Generalized Additive Models for Location, Scale and Shape (GAMLSS) which allow incorporating a variable dispersion. We analysed tick burden of 78 roe deer, sampled in a forest region of Germany over a period of 20 months. Assuming a negative binomial error distribution and controlling for ambient temperature, we analysed whether host sex and body mass affected individual tick burdens. Models for larval and nymphal tick burden included host sex, with male hosts being more heavily infested than female ones. However, the influence of host sex on immature tick burden was associated with wide standard errors (nymphs) or the factor was marginally significant (larvae). Adult tick burden was positively correlated with host body mass. Thus, controlled for host body mass and ambient temperature, there is weak support for sex-biased parasitism in this system. Compared with models which assume linear relationships, GAMLSS provided a better fit. Adding a variable dispersion term improved only one of the four models. Yet, the potential of modelling dispersion as a function of variables appears promising for larger datasets. © 2010 The Authors. Medical and Veterinary Entomology © 2010 The Royal Entomological Society.

  15. Analytical Approach for Estimating Preliminary Mass of ARES I Crew Launch Vehicle Upper Stage Structural Components

    Science.gov (United States)

    Aggarwal, Pravin

    2007-01-01

    electrical power functions to other Elements of the CLV, is included as secondary structure. The MSFC has an overall responsibility for the integrated US element as well as structural design an thermal control of the fuel tanks, intertank, interstage, avionics, main propulsion system, Reaction Control System (RCS) for both the Upper Stage and the First Stage. MSFC's Spacecraft and Vehicle Department, Structural and Analysis Design Division is developing a set of predicted mass of these elements. This paper details the methodology, criterion and tools used for the preliminary mass predictions of the upper stage structural assembly components. In general, weight of the cylindrical barrel sections are estimated using the commercial code Hypersizer, whereas, weight of the domes are developed using classical solutions. HyperSizer is software that performs automated structural analysis and sizing optimization based on aerospace methods for strength, stability, and stiffness. Analysis methods range from closed form, traditional hand calculations repeated every day in industry to more advanced panel buckling algorithms. Margin-of-safety reporting for every potential failure provides the engineer with a powerful insight into the structural problem. Optimization capabilities include finding minimum weight panel or beam concepts, material selections, cross sectional dimensions, thicknesses, and lay-ups from a library of 40 different stiffened and sandwich designs and a database of composite, metallic, honeycomb, and foam materials. Multiple different concepts (orthogrid, isogrid, and skin stiffener) were run for multiple loading combinations of ascent design load with and with out tank pressure as well as proof pressure condition. Subsequently, selected optimized concept obtained from Hypersizer runs was translated into a computer aid design (CAD) model to account for the wall thickness tolerance, weld land etc for developing the most probable weight of the components. The flow diram

  16. Mass transfer simulation of nanofiltration membranes for electrolyte solutions through generalized Maxwell-Stefan approach

    International Nuclear Information System (INIS)

    Hoshyargar, Vahid; Fadaei, Farzad; Ashrafizadeh, Seyed Nezameddin

    2015-01-01

    A comprehensive mathematical model is developed for simulation of ion transport through nanofiltration membranes. The model is based on the Maxwell-Stefan approach and takes into account steric, Donnan, and dielectric effects in the transport of mono and divalent ions. Theoretical ion rejection for multi-electrolyte mixtures was obtained by numerically solving the 'hindered transport' based on the generalized Maxwell-Stefan equation for the flux of ions. A computer simulation has been developed to predict the transport in the range of nanofiltration, a numerical procedure developed linearization and discretization form of the governing equations, and the finite volume method was employed for the numerical solution of equations. The developed numerical method is capable of solving equations for multicomponent systems of n species no matter to what extent the system shows stiffness. The model findings were compared and verified with the experimental data from literature for two systems of Na 2 SO 4 +NaCl and MgCl 2 +NaCl. Comparison showed great agreement for different concentrations. As such, the model is capable of predicting the rejection of different ions at various concentrations. The advantage of such a model is saving costs as a result of minimizing the number of required experiments, while it is closer to a realistic situation since the adsorption of ions has been taken into account. Using this model, the flux of permeates and rejections of multi-component liquid feeds can be calculated as a function of membrane properties. This simulation tool attempts to fill in the gap in methods used for predicting nanofiltration and optimization of the performance of charged nanofilters through generalized Maxwell-Stefan (GMS) approach. The application of the current model may weaken the latter gap, which has arisen due to the complexity of the fundamentals of ion transport processes via this approach, and may further facilitate the industrial development of

  17. A novel approach to signal normalisation in atmospheric pressure ionisation mass spectrometry.

    Science.gov (United States)

    Vogeser, Michael; Kirchhoff, Fabian; Geyer, Roland

    2012-07-01

    The aim of our study was to test an alternative principle of signal normalisation in LC-MS/MS. During analyses, post column infusion of the target analyte is done via a T-piece, generating an "area under the analyte peak" (AUP). The ratio of peak area to AUP is assessed as assay response. Acceptable analytical performance of this principle was found for an exemplary analyte. Post-column infusion may allow normalisation of ion suppression not requiring any additional standard compound. This approach can be useful in situations where no appropriate compound is available for classical internal standardisation. Copyright © 2012 Elsevier B.V. All rights reserved.

  18. Comparative mass spectrometry & nuclear magnetic resonance metabolomic approaches for nutraceuticals quality control analysis: a brief review.

    Science.gov (United States)

    Farag, Mohamed A

    2014-01-01

    The number of botanical dietary supplements in the market has recently increased primarily due to increased health awareness. Standardization and quality control of the constituents of these plant extracts is an important topic, particularly when such ingredients are used long term as dietary supplements, or in cases where higher doses are marketed as drugs. The development of fast, comprehensive, and effective untargeted analytical methods for plant extracts is of high interest. Nuclear magnetic resonance spectroscopy and mass spectrometry are the most informative tools, each of which enables high-throughput and global analysis of hundreds of metabolites in a single step. Although only one of the two techniques is utilized in the majority of plant metabolomics applications, there is a growing interest in combining the data from both platforms to effectively unravel the complexity of plant samples. The application of combined MS and NMR in the quality control of nutraceuticals forms the major part of this review. Finally I will look at the future developments and perspectives of these two technologies for the quality control of herbal materials.

  19. Identification of okadaic acid-induced phosphorylation events by a mass spectrometry approach

    International Nuclear Information System (INIS)

    Hill, Jennifer J.; Callaghan, Deborah A.; Ding Wen; Kelly, John F.; Chakravarthy, Balu R.

    2006-01-01

    Okadaic acid (OA) is a widely used small-molecule phosphatase inhibitor that is thought to selectively inhibit protein phosphatase 2A (PP2A). Multiple studies have demonstrated that PP2A activity is compromised in Brains of Alzheimer's disease patients. Thus, we set out to determine changes in phosphorylation that occur upon OA treatment of neuronal cells. Utilizing isotope-coded affinity tags and mass spectrometry analysis, we determined the relative abundance of proteins in a phosphoprotein enriched fraction from control and OA-treated primary cortical neurons. We identified many proteins whose phosphorylation state is regulated by OA, including glycogen synthase kinase 3β, collapsin-response mediator proteins (DRP-2, DPYSL-5, and CRMP-4), and the B subunit of PP2A itself. Most interestingly, we have found that complexin 2, an important regulator of neurotransmitter release and synaptic plasticity, is phosphorylated at serine 93 upon OA treatment of neurons. This is First report of a phosphorylation site on complexin 2

  20. Normalization Approaches for Removing Systematic Biases Associated with Mass Spectrometry and Label-Free Proteomics

    Energy Technology Data Exchange (ETDEWEB)

    Callister, Stephen J.; Barry, Richard C.; Adkins, Joshua N.; Johnson, Ethan T.; Qian, Weijun; Webb-Robertson, Bobbie-Jo M.; Smith, Richard D.; Lipton, Mary S.

    2006-02-01

    Central tendency, linear regression, locally weighted regression, and quantile techniques were investigated for normalization of peptide abundance measurements obtained from high-throughput liquid chromatography-Fourier transform ion cyclotron resonance mass spectrometry (LC-FTICR MS). Arbitrary abundances of peptides were obtained from three sample sets, including a standard protein sample, two Deinococcus radiodurans samples taken from different growth phases, and two mouse striatum samples from control and methamphetamine-stressed mice (strain C57BL/6). The selected normalization techniques were evaluated in both the absence and presence of biological variability by estimating extraneous variability prior to and following normalization. Prior to normalization, replicate runs from each sample set were observed to be statistically different, while following normalization replicate runs were no longer statistically different. Although all techniques reduced systematic bias, assigned ranks among the techniques revealed significant trends. For most LC-FTICR MS analyses, linear regression normalization ranked either first or second among the four techniques, suggesting that this technique was more generally suitable for reducing systematic biases.

  1. Stationarity and periodicities of linear speed of coronal mass ejection: a statistical signal processing approach

    Science.gov (United States)

    Chattopadhyay, Anirban; Khondekar, Mofazzal Hossain; Bhattacharjee, Anup Kumar

    2017-09-01

    In this paper initiative has been taken to search the periodicities of linear speed of Coronal Mass Ejection in solar cycle 23. Double exponential smoothing and Discrete Wavelet Transform are being used for detrending and filtering of the CME linear speed time series. To choose the appropriate statistical methodology for the said purpose, Smoothed Pseudo Wigner-Ville distribution (SPWVD) has been used beforehand to confirm the non-stationarity of the time series. The Time-Frequency representation tool like Hilbert Huang Transform and Empirical Mode decomposition has been implemented to unearth the underneath periodicities in the non-stationary time series of the linear speed of CME. Of all the periodicities having more than 95% Confidence Level, the relevant periodicities have been segregated out using Integral peak detection algorithm. The periodicities observed are of low scale ranging from 2-159 days with some relevant periods like 4 days, 10 days, 11 days, 12 days, 13.7 days, 14.5 and 21.6 days. These short range periodicities indicate the probable origin of the CME is the active longitude and the magnetic flux network of the sun. The results also insinuate about the probable mutual influence and causality with other solar activities (like solar radio emission, Ap index, solar wind speed, etc.) owing to the similitude between their periods and CME linear speed periods. The periodicities of 4 days and 10 days indicate the possible existence of the Rossby-type waves or planetary waves in Sun.

  2. A scale space approach for unsupervised feature selection in mass spectra classification for ovarian cancer detection.

    Science.gov (United States)

    Ceccarelli, Michele; d'Acierno, Antonio; Facchiano, Angelo

    2009-10-15

    Mass spectrometry spectra, widely used in proteomics studies as a screening tool for protein profiling and to detect discriminatory signals, are high dimensional data. A large number of local maxima (a.k.a. peaks) have to be analyzed as part of computational pipelines aimed at the realization of efficient predictive and screening protocols. With this kind of data dimensions and samples size the risk of over-fitting and selection bias is pervasive. Therefore the development of bio-informatics methods based on unsupervised feature extraction can lead to general tools which can be applied to several fields of predictive proteomics. We propose a method for feature selection and extraction grounded on the theory of multi-scale spaces for high resolution spectra derived from analysis of serum. Then we use support vector machines for classification. In particular we use a database containing 216 samples spectra divided in 115 cancer and 91 control samples. The overall accuracy averaged over a large cross validation study is 98.18. The area under the ROC curve of the best selected model is 0.9962. We improved previous known results on the problem on the same data, with the advantage that the proposed method has an unsupervised feature selection phase. All the developed code, as MATLAB scripts, can be downloaded from http://medeaserver.isa.cnr.it/dacierno/spectracode.htm.

  3. A CD45-based barcoding approach to multiplex mass-cytometry (CyTOF).

    Science.gov (United States)

    Lai, Liyun; Ong, Raymond; Li, Juntao; Albani, Salvatore

    2015-04-01

    CyTOF enables the study of the immune system with a complexity, depth, and multidimensionality never achieved before. However, the full potential of using CyTOF can be limited by scarce cell samples. Barcoding strategies developed based on direct labeling of cells using maleimido-monoamide-DOTA (m-DOTA) provide a very useful tool. However, using m-DOTA has some inherent problems, mainly associated with signal intensity. This may be a source of uncertainty when samples are multiplexed. As an alternative or complementary approach to m-DOTA, conjugating an antibody, specific for a membrane protein present on most immune cells, with different isotopes could address the issues of stability and signal intensity needed for effective barcoding. We chose for this purpose CD45, and designed experiments to address different types of cultures and the ability to detect extra- and intra-cellular targets. We show here that our approach provides an useful alternative to m-DOTA in terms of sensitivity, specificity, flexibility, and user-friendliness. Our manuscript provides details to effectively barcode immune cells, overcoming limitations in current technology and enabling the use of CyTOF with scarce samples (for instance precious clinical samples). © 2015 The Authors. Published by Wiley Periodicals, Inc.

  4. Mass balance modelling of contaminants in river basins: a flexible matrix approach.

    Science.gov (United States)

    Warren, Christopher; Mackay, Don; Whelan, Mick; Fox, Kay

    2005-12-01

    A novel and flexible approach is described for simulating the behaviour of chemicals in river basins. A number (n) of river reaches are defined and their connectivity is described by entries in an n x n matrix. Changes in segmentation can be readily accommodated by altering the matrix entries, without the need for model revision. Two models are described. The simpler QMX-R model only considers advection and an overall loss due to the combined processes of volatilization, net transfer to sediment and degradation. The rate constant for the overall loss is derived from fugacity calculations for a single segment system. The more rigorous QMX-F model performs fugacity calculations for each segment and explicitly includes the processes of advection, evaporation, water-sediment exchange and degradation in both water and sediment. In this way chemical exposure in all compartments (including equilibrium concentrations in biota) can be estimated. Both models are designed to serve as intermediate-complexity exposure assessment tools for river basins with relatively low data requirements. By considering the spatially explicit nature of emission sources and the changes in concentration which occur with transport in the channel system, the approach offers significant advantages over simple one-segment simulations while being more readily applicable than more sophisticated, highly segmented, GIS-based models.

  5. Impacts of invasive earthworms on soil mercury cycling: Two mass balance approaches to an earthworm invasion in a northern Minnesota forest

    Science.gov (United States)

    Sona Psarska; Edward A. Nater; Randy Kolka

    2016-01-01

    Invasive earthworms perturb natural forest ecosystems that initially developed without them, mainly by consuming the forest floor (an organic rich surficial soil horizon) and by mixing the upper parts of the soil. The fate of mercury (Hg) formerly contained in the forest floor is largely unknown. We used two mass balance approaches (simple mass balance and geochemical...

  6. Meeting Radiation Protection Requirements and Reducing Spacecraft Mass - A Multifunctional Materials Approach

    Science.gov (United States)

    Atwell, William; Koontz, Steve; Reddell, Brandon; Rojdev, Kristina; Franklin, Jennifer

    2010-01-01

    Both crew and radio-sensitive systems, especially electronics must be protected from the effects of the space radiation environment. One method of mitigating this radiation exposure is to use passive-shielding materials. In previous vehicle designs such as the International Space Station (ISS), materials such as aluminum and polyethylene have been used as parasitic shielding to protect crew and electronics from exposure, but these designs add mass and decrease the amount of usable volume inside the vehicle. Thus, it is of interest to understand whether structural materials can also be designed to provide the radiation shielding capability needed for crew and electronics, while still providing weight savings and increased useable volume when compared against previous vehicle shielding designs. In this paper, we present calculations and analysis using the HZETRN (deterministic) and FLUKA (Monte Carlo) codes to investigate the radiation mitigation properties of these structural shielding materials, which includes graded-Z and composite materials. This work is also a follow-on to an earlier paper, that compared computational results for three radiation transport codes, HZETRN, HETC, and FLUKA, using the Feb. 1956 solar particle event (SPE) spectrum. In the following analysis, we consider the October 1989 Ground Level Enhanced (GLE) SPE as the input source term based on the Band function fitting method. Using HZETRN and FLUKA, parametric absorbed doses at the center of a hemispherical structure on the lunar surface are calculated for various thicknesses of graded-Z layups and an all-aluminum structure. HZETRN and FLUKA calculations are compared and are in reasonable (18% to 27%) agreement. Both codes are in agreement with respect to the predicted shielding material performance trends. The results from both HZETRN and FLUKA are analyzed and the radiation protection properties and potential weight savings of various materials and materials lay-ups are compared.

  7. Mature forms of the major seed storage albumins in sunflower: A mass spectrometric approach.

    Science.gov (United States)

    Franke, Bastian; Colgrave, Michelle L; Mylne, Joshua S; Rosengren, K Johan

    2016-09-16

    Seed storage albumins are abundant, water-soluble proteins that are degraded to provide critical nutrients for the germinating seedling. It has been established that the sunflower albumins encoded by SEED STORAGE ALBUMIN 2 (SESA2), SESA20 and SESA3 are the major components of the albumin-rich fraction of the common sunflower Helianthus annuus. To determine the structure of sunflowers most important albumins we performed a detailed chromatographic and mass spectrometric characterization to assess what post-translational processing they receive prior to deposition in the protein storage vacuole. We found that SESA2 and SESA20 each encode two albumins. The first of the two SESA2 albumins (SESA2-1) exists as a monomer of 116 or 117 residues, differing by a threonine at the C-terminus. The second of the two SESA2 albumins (SESA2-2) is a monomer of 128 residues. SESA20 encodes the albumin SESA20-2, which is a 127-residue monomer, whereas SESA20-1 was not abundant enough to be structurally described. SESA3, which has been partly characterized previously, was found in several forms with methylation of its asparagine residues. In contrast to other dicot albumins, which are generally matured into a heterodimer, all the dominant mature sunflower albumins SESA2, SESA20-2, SESA3 and its post-translationally modified analogue SESA3-a are monomeric. Sunflower plants have been bred to thrive in various climate zones making them favored crops to meet the growing worldwide demand by humans for protein. The abundance of seed storage proteins makes them an important source of protein for animal and human nutrition. This study explores the structures of the dominant sunflower napin-type seed storage albumins to understand what structures evolution has favored in the most abundant proteins in sunflower seed. Crown Copyright © 2016. Published by Elsevier B.V. All rights reserved.

  8. Evolution of a Lowland Karst Landscape; A Mass-Balance Approach

    Science.gov (United States)

    Chamberlin, C.; Heffernan, J. B.; Cohen, M. J.; Quintero, C.; Pain, A.

    2016-12-01

    Karst landscapes are highly soluble, and are vulnerable to biological acid production as a major driving factor in their evolution. Big Cypress National Park (BICY) is a low-lying karst landscape in southern Florida displaying a distinctive morphology of isolated depressions likely influenced by biology. The goal of this study is to constrain timescales of landform development in BICY. This question was addressed through the construction of landscape-scale elemental budgets for both calcium and phosphorus. Precipitation and export fluxes were calculated using available chemistry and hydrology data, and stocks were calculated from a combination of existing data, field measurements, and laboratory chemical analysis. Estimates of expected mass export given no biological acid production and given an equivalent production of 100% of GPP were compared with observed rates. Current standing stocks of phosphorus are dominated by a large soil pool, and contain 500 Gg P. Inputs are largely dominated by precipitation, and 8000 years are necessary to accumulate standing stocks of phosphorus given modern fluxes. Calcium flux is vastly dominated by dissolution of the limestone bedrock, and though some calcium is retained in the soil, most is exported. Using LiDAR generated estimates of volume loss across the landscape and current export rates, an estimated 15,000 years would be necessary to create the modern landscape. Both of these estimates indicate that the BICY landscape is geologically very young. The different behaviors of these elements (calcium is largely exported, while phosphorus is largely retained) lend additional confidence to estimates of denudation rates of the landscape. These estimates can be even closer reconciled if calcium redistribution over the landscape is allowed for. This estimate is compared to the two bounding conditions for biological weathering to indicate a likely level of biological importance to landscape development in this system.

  9. Mass renormalization and unconventional pairing in multi-band Fe-based superconductors- a phenomenological approach

    Energy Technology Data Exchange (ETDEWEB)

    Drechsler, S.L.; Efremov, D.; Grinenko, V. [IFW-Dresden (Germany); Johnston, S. [Inst. of Quantum Matter, University of British Coulumbia, Vancouver (Canada); Rosner, H. [MPI-cPfS, Dresden, (Germany); Kikoin, K. [Tel Aviv University (Israel)

    2015-07-01

    Combining DFT calculations of the density of states and plasma frequencies with experimental thermodynamic, optical, ARPES, and dHvA data taken from the literature, we estimate both the high-energy (Coulomb, Hund's rule coupling) and the low-energy (el-boson coupling) electronic mass renormalization [H(L)EMR] for typical Fe-pnictides with T{sub c}<40 K, focusing on (K,Rb,Cs)Fe{sub 2}As{sub 2}, (Ca,Na)122, (Ba,K)122, LiFeAs, and LaFeO{sub 1-x}F{sub x}As with and without As-vacancies. Using Eliashberg theory we show that these systems can NOT be described by a very strong el-boson coupling constant λ ≥ ∝ 2, being in conflict with the HEMR as seen by DMFT, ARPES and optics. Instead, an intermediate s{sub ±} coupling regime is realized, mainly based on interband spin fluctuations from one predominant pair of bands. For (Ca,Na)122, there is also a non-negligible intraband el-phonon/orbital fluctuation intraband contribution. The coexistence of magnetic As-vacancies and high-T{sub c}=28 K for LaFeO{sub 1-x}F{sub x}As{sub 1-δ} excludes an orbital fluctuation dominated s{sub ++} scenario at least for that system. In contrast, the line nodal BaFe{sub 2}(As,P){sub 2} near the quantum critical point is found as a superstrongly coupled system. The role of a pseudo-gap is briefly discussed for some of these systems.

  10. Thirty years of precise gravity measurements at Mt. Vesuvius: an approach to detect underground mass movements

    Directory of Open Access Journals (Sweden)

    Giovanna Berrino

    2013-11-01

    Full Text Available Since 1982, high precision gravity measurements have been routinely carried out on Mt. Vesuvius. The gravity network consists of selected sites most of them coinciding with, or very close to, leveling benchmarks to remove the effect of the elevation changes from gravity variations. The reference station is located in Napoli, outside the volcanic area. Since 1986, absolute gravity measurements have been periodically made on a station on Mt. Vesuvius, close to a permanent gravity station established in 1987, and at the reference in Napoli. The results of the gravity measurements since 1982 are presented and discussed. Moderate gravity changes on short-time were generally observed. On long-term significant gravity changes occurred and the overall fields displayed well defined patterns. Several periods of evolution may be recognized. Gravity changes revealed by the relative surveys have been confirmed by repeated absolute measurements, which also confirmed the long-term stability of the reference site. The gravity changes over the recognized periods appear correlated with the seismic crises and with changes of the tidal parameters obtained by continuous measurements. The absence of significant ground deformation implies masses redistribution, essentially density changes without significant volume changes, such as fluids migration at the depth of the seismic foci, i.e. at a few kilometers. The fluid migration may occur through pre-existing geological structures, as also suggested by hydrological studies, and/or through new fractures generated by seismic activity. This interpretation is supported by the analyses of the spatial gravity changes overlapping the most significant and recent seismic crises.

  11. Migration of antioxidants from polylactic acid films: A parameter estimation approach and an overview of the current mass transfer models.

    Science.gov (United States)

    Samsudin, Hayati; Auras, Rafael; Mishra, Dharmendra; Dolan, Kirk; Burgess, Gary; Rubino, Maria; Selke, Susan; Soto-Valdez, Herlinda

    2018-01-01

    Migration studies of chemicals from contact materials have been widely conducted due to their importance in determining the safety and shelf life of a food product in their packages. The US Food and Drug Administration (FDA) and the European Food Safety Authority (EFSA) require this safety assessment for food contact materials. So, migration experiments are theoretically designed and experimentally conducted to obtain data that can be used to assess the kinetics of chemical release. In this work, a parameter estimation approach was used to review and to determine the mass transfer partition and diffusion coefficients governing the migration process of eight antioxidants from poly(lactic acid), PLA, based films into water/ethanol solutions at temperatures between 20 and 50°C. Scaled sensitivity coefficients were calculated to assess simultaneously estimation of a number of mass transfer parameters. An optimal experimental design approach was performed to show the importance of properly designing a migration experiment. Additional parameters also provide better insights on migration of the antioxidants. For example, the partition coefficients could be better estimated using data from the early part of the experiment instead at the end. Experiments could be conducted for shorter periods of time saving time and resources. Diffusion coefficients of the eight antioxidants from PLA films were between 0.2 and 19×10 -14 m 2 /s at ~40°C. The use of parameter estimation approach provided additional and useful insights about the migration of antioxidants from PLA films. Copyright © 2017 Elsevier Ltd. All rights reserved.

  12. Reconciling ocean mass content change based on direct and inverse approaches by utilizing data from GRACE, altimetry and Swarm

    Science.gov (United States)

    Rietbroek, R.; Uebbing, B.; Lück, C.; Kusche, J.

    2017-12-01

    Ocean mass content (OMC) change due to the melting of the ice-sheets in Greenland and Antarctica, melting of glaciers and changes in terrestrial hydrology is a major contributor to present-day sea level rise. Since 2002, the GRACE satellite mission serves as a valuable tool for directly measuring the variations in OMC. As GRACE has almost reached the end of its lifetime, efforts are being made to utilize the Swarm mission for the recovery of low degree time-variable gravity fields to bridge a possible gap until the GRACE-FO mission and to fill up periods where GRACE data was not existent. To this end we compute Swarm monthly normal equations and spherical harmonics that are found competitive to other solutions. In addition to directly measuring the OMC, combination of GRACE gravity data with altimetry data in a global inversion approach allows to separate the total sea level change into individual mass-driven and steric contributions. However, published estimates of OMC from the direct and inverse methods differ not only depending on the time window, but also are influenced by numerous post-processing choices. Here, we will look into sources of such differences between direct and inverse approaches and evaluate the capabilities of Swarm to derive OMC. Deriving time series of OMC requires several processing steps; choosing a GRACE (and altimetry) product, data coverage, masks and filters to be applied in either spatial or spectral domain, corrections related to spatial leakage, GIA and geocenter motion. In this study, we compare and quantify the effects of the different processing choices of the direct and inverse methods. Our preliminary results point to the GIA correction as the major source of difference between the two approaches.

  13. An integrated approach for determining plutonium mass in spent fuel assemblies with nondestructive assay

    International Nuclear Information System (INIS)

    Swinhoe, Martyn T.; Tobin, Stephen J.; Fensin, Mike L.; Menlove, Howard O.

    2009-01-01

    There are a variety of reasons for quantifying plutonium (Pu) in spent fuel. Below, five motivations are listed: (1) To verify the Pu content of spent fuel without depending on unverified information from the facility, as requested by the IAEA ('independent verification'). New spent fuel measurement techniques have the potential to allow the IAEA to recover continuity of knowledge and to better detect diversion. (2) To assure regulators that all of the nuclear material of interest leaving a nuclear facility actually arrives at another nuclear facility ('shipper/receiver'). Given the large stockpile of nuclear fuel at reactor sites around the world, it is clear that in the coming decades, spent fuel will need to be moved to either reprocessing facilities or storage sites. Safeguarding this transportation is of significant interest. (3) To quantify the Pu in spent fuel that is not considered 'self-protecting.' Fuel is considered self-protecting by some regulatory bodies when the dose that the fuel emits is above a given level. If the fuel is not self-protecting, then the Pu content of the fuel needs to be determined and the Pu mass recorded in the facility's accounting system. This subject area is of particular interest to facilities that have research-reactor spent fuel or old light-water reactor (LWR) fuel. It is also of interest to regulators considering changing the level at which fuel is considered self-protecting. (4) To determine the input accountability value at an electrochemical processing facility. It is not expected that an electrochemical reprocessing facility will have an input accountability tank, as is typical in an aqueous reprocessing facility. As such, one possible means of determining the input accountability value is to measure the Pu content in the spent fuel that arrives at the facility. (5) To fully understand the composition of the fuel in order to efficiently and safely pack spent fuel into a long-term repository. The NDA of spent fuel can

  14. A Multi-Step Approach to Assessing LIGO Test Mass Coatings

    Science.gov (United States)

    Glover, Lamar; Goff, Michael; Linker, Seth; Neilson, Joshua; Patel, Jignesh; Pinto, Innocenzo; Principe, Maria; Villarama, Ethan; Arriaga, Eddy; Barragan, Erik; Chao, Shiuh; Daneshgaran, Lara; DeSalvo, Riccardo; Do, Eric; Fajardo, Cameron

    2018-02-01

    Photographs of the LIGO Gravitational Wave detector mirrors illuminated by the standing beam were analyzed with an astronomical software tool designed to identify stars within images, which extracted hundreds of thousands of point-like scatterers uniformly distributed across the mirror surface, likely distributed through the depth of the coating layers. The sheer number of the observed scatterers implies a fundamental, thermodynamic origin during deposition or processing. If identified as crystallites, these scatterers would be a possible source of the mirror dissipation and thermal noise, which limit the sensitivity of observatories to Gravitational Waves. In order to learn more about the composition and location of the detected scatterers, a feasibility study is underway to develop a method that determines the location of the scatterers by producing a complete mapping of scatterers within test samples, including their depth distribution, optical amplitude distribution, and lateral distribution. Also, research is underway to accurately identify future materials and/or coating methods that possess the largest possible mechanical quality factor (Q). Current efforts propose a new experimental approach that will more precisely measure the Q of coatings by depositing them onto 100 nm Silicon Nitride membranes.

  15. A review of research on cytological approach in salivary gland masses

    Directory of Open Access Journals (Sweden)

    Arvind Babu Rajendra Santosh

    2018-01-01

    Full Text Available To evaluate the diagnostic accuracy of fine-needle aspirations (FNAs in salivary gland pathologies. A comprehensive literature search was conducted in the PubMed database using related Medical Subject Heading terms “sensitivity and specificity of FNA in salivary gland” and “diagnostic accuracy of FNA in salivary gland” for the period 1980–2016, and we found that 414 research studies had been published. PRISMA technology was utilized to prepare flow chart for displaying data search strategy. A total of 385 articles were excluded based on the established inclusion and exclusion criteria of the study. Twenty-nine research studies were included. Those twenty-nine studies on the sensitivity and specificity of FNAs in salivary gland pathology consisted of 5274 cases of benign, malignant and inflammatory salivary gland lesions. The present study identified a range of 87%–100% sensitivity and 90%–100% specificity for the usefulness of FNAs in distinguishing benign and malignant salivary gland lesions. Although a considerable number of studies have been identified that reported on sensitivity and specificity of FNAs in salivary gland pathologies, each study had a different approach in reporting the sensitivity and specificity. We emphasize that standardized reporting protocols of sensitivity and specificity report supported with checklists would help future researchers to interpret this cytological method and make more accurate clinical utility and usefulness reports on salivary gland pathologies.

  16. A new insert sample approach to paper spray mass spectrometry: a paper substrate with paraffin barriers.

    Science.gov (United States)

    Colletes, T C; Garcia, P T; Campanha, R B; Abdelnur, P V; Romão, W; Coltro, W K T; Vaz, B G

    2016-03-07

    The analytical performance for paper spray (PS) using a new insert sample approach based on paper with paraffin barriers (PS-PB) is presented. The paraffin barrier is made using a simple, fast and cheap method based on the stamping of paraffin onto a paper surface. Typical operation conditions of paper spray such as the solvent volume applied on the paper surface, and the paper substrate type are evaluated. A paper substrate with paraffin barriers shows better performance on analysis of a range of typical analytes when compared to the conventional PS-MS using normal paper (PS-NP) and PS-MS using paper with two rounded corners (PS-RC). PS-PB was applied to detect sugars and their inhibitors in sugarcane bagasse liquors from a second generation ethanol process. Moreover, the PS-PB proved to be excellent, showing results for the quantification of glucose in hydrolysis liquors with excellent linearity (R(2) = 0.99), limits of detection (2.77 mmol L(-1)) and quantification (9.27 mmol L(-1)). The results are better than for PS-NP and PS-RC. The PS-PB was also excellent in performance when compared with the HPLC-UV method for glucose quantification on hydrolysis of liquor samples.

  17. A mass spectrometry proteomics data management platform.

    Science.gov (United States)

    Sharma, Vagisha; Eng, Jimmy K; Maccoss, Michael J; Riffle, Michael

    2012-09-01

    Mass spectrometry-based proteomics is increasingly being used in biomedical research. These experiments typically generate a large volume of highly complex data, and the volume and complexity are only increasing with time. There exist many software pipelines for analyzing these data (each typically with its own file formats), and as technology improves, these file formats change and new formats are developed. Files produced from these myriad software programs may accumulate on hard disks or tape drives over time, with older files being rendered progressively more obsolete and unusable with each successive technical advancement and data format change. Although initiatives exist to standardize the file formats used in proteomics, they do not address the core failings of a file-based data management system: (1) files are typically poorly annotated experimentally, (2) files are "organically" distributed across laboratory file systems in an ad hoc manner, (3) files formats become obsolete, and (4) searching the data and comparing and contrasting results across separate experiments is very inefficient (if possible at all). Here we present a relational database architecture and accompanying web application dubbed Mass Spectrometry Data Platform that is designed to address the failings of the file-based mass spectrometry data management approach. The database is designed such that the output of disparate software pipelines may be imported into a core set of unified tables, with these core tables being extended to support data generated by specific pipelines. Because the data are unified, they may be queried, viewed, and compared across multiple experiments using a common web interface. Mass Spectrometry Data Platform is open source and freely available at http://code.google.com/p/msdapl/.

  18. Comparison of surface mass balance of ice sheets simulated by positive-degree-day method and energy balance approach

    Directory of Open Access Journals (Sweden)

    E. Bauer

    2017-07-01

    Full Text Available Glacial cycles of the late Quaternary are controlled by the asymmetrically varying mass balance of continental ice sheets in the Northern Hemisphere. Surface mass balance is governed by processes of ablation and accumulation. Here two ablation schemes, the positive-degree-day (PDD method and the surface energy balance (SEB approach, are compared in transient simulations of the last glacial cycle with the Earth system model of intermediate complexity CLIMBER-2. The standard version of the CLIMBER-2 model incorporates the SEB approach and simulates ice volume variations in reasonable agreement with paleoclimate reconstructions during the entire last glacial cycle. Using results from the standard CLIMBER-2 model version, we simulated ablation with the PDD method in offline mode by applying different combinations of three empirical parameters of the PDD scheme. We found that none of the parameter combinations allow us to simulate a surface mass balance of the American and European ice sheets that is similar to that obtained with the standard SEB method. The use of constant values for the empirical PDD parameters led either to too much ablation during the first phase of the last glacial cycle or too little ablation during the final phase. We then substituted the standard SEB scheme in CLIMBER-2 with the PDD scheme and performed a suite of fully interactive (online simulations of the last glacial cycle with different combinations of PDD parameters. The results of these simulations confirmed the results of the offline simulations: no combination of PDD parameters realistically simulates the evolution of the ice sheets during the entire glacial cycle. The use of constant parameter values in the online simulations leads either to a buildup of too much ice volume at the end of glacial cycle or too little ice volume at the beginning. Even when the model correctly simulates global ice volume at the last glacial maximum (21 ka, it is unable to simulate

  19. Protein biomarkers on tissue as imaged via MALDI mass spectrometry: A systematic approach to study the limits of detection.

    Science.gov (United States)

    van de Ven, Stephanie M W Y; Bemis, Kyle D; Lau, Kenneth; Adusumilli, Ravali; Kota, Uma; Stolowitz, Mark; Vitek, Olga; Mallick, Parag; Gambhir, Sanjiv S

    2016-06-01

    MALDI mass spectrometry imaging (MSI) is emerging as a tool for protein and peptide imaging across tissue sections. Despite extensive study, there does not yet exist a baseline study evaluating the potential capabilities for this technique to detect diverse proteins in tissue sections. In this study, we developed a systematic approach for characterizing MALDI-MSI workflows in terms of limits of detection, coefficients of variation, spatial resolution, and the identification of endogenous tissue proteins. Our goal was to quantify these figures of merit for a number of different proteins and peptides, in order to gain more insight in the feasibility of protein biomarker discovery efforts using this technique. Control proteins and peptides were deposited in serial dilutions on thinly sectioned mouse xenograft tissue. Using our experimental setup, coefficients of variation were biomarkers and a new benchmarking strategy that can be used for comparing diverse MALDI-MSI workflows. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  20. Migration of antioxidants from polylactic acid films, a parameter estimation approach: Part I - A model including convective mass transfer coefficient.

    Science.gov (United States)

    Samsudin, Hayati; Auras, Rafael; Burgess, Gary; Dolan, Kirk; Soto-Valdez, Herlinda

    2018-03-01

    A two-step solution based on the boundary conditions of Crank's equations for mass transfer in a film was developed. Three driving factors, the diffusion (D), partition (K p,f ) and convective mass transfer coefficients (h), govern the sorption and/or desorption kinetics of migrants from polymer films. These three parameters were simultaneously estimated. They provide in-depth insight into the physics of a migration process. The first step was used to find the combination of D, K p,f and h that minimized the sums of squared errors (SSE) between the predicted and actual results. In step 2, an ordinary least square (OLS) estimation was performed by using the proposed analytical solution containing D, K p,f and h. Three selected migration studies of PLA/antioxidant-based films were used to demonstrate the use of this two-step solution. Additional parameter estimation approaches such as sequential and bootstrap were also performed to acquire a better knowledge about the kinetics of migration. The proposed model successfully provided the initial guesses for D, K p,f and h. The h value was determined without performing a specific experiment for it. By determining h together with D, under or overestimation issues pertaining to a migration process can be avoided since these two parameters are correlated. Copyright © 2017 Elsevier Ltd. All rights reserved.

  1. Determination of Selected Polycyclic Aromatic Compounds in Particulate Matter Samples with Low Mass Loading: An Approach to Test Method Accuracy

    Directory of Open Access Journals (Sweden)

    Susana García-Alonso

    2017-01-01

    Full Text Available A miniaturized analytical procedure to determine selected polycyclic aromatic compounds (PACs in low mass loadings (<10 mg of particulate matter (PM is evaluated. The proposed method is based on a simple sonication/agitation method using small amounts of solvent for extraction. The use of a reduced sample size of particulate matter is often limiting for allowing the quantification of analytes. This also leads to the need for changing analytical procedures and evaluating its performance. The trueness and precision of the proposed method were tested using ambient air samples. Analytical results from the proposed method were compared with those of pressurized liquid and microwave extractions. Selected PACs (polycyclic aromatic hydrocarbons (PAHs and nitro polycyclic aromatic hydrocarbons (NPAHs were determined by liquid chromatography with fluorescence detection (HPLC/FD. Taking results from pressurized liquid extractions as reference values, recovery rates of sonication/agitation method were over 80% for the most abundant PAHs. Recovery rates of selected NPAHs were lower. Enhanced rates were obtained when methanol was used as a modifier. Intermediate precision was estimated by data comparison from two mathematical approaches: normalized difference data and pooled relative deviations. Intermediate precision was in the range of 10–20%. The effectiveness of the proposed method was evaluated in PM aerosol samples collected with very low mass loadings (<0.2 mg during characterization studies from turbofan engine exhausts.

  2. Targeted and untargeted high resolution mass approach for a putative profiling of glycosylated simple phenols in hybrid grapes.

    Science.gov (United States)

    Barnaba, Chiara; Dellacassa, Eduardo; Nicolini, Giorgio; Giacomelli, Mattia; Roman Villegas, Tomas; Nardin, Tiziana; Larcher, Roberto

    2017-08-01

    Vitis vinifera is one of the most widespread grapevines around the world representing the raw material for high quality wine production. The availability of more resistant interspecific hybrid vine varieties, developed from crosses between Vitis vinifera and other Vitis species, has generated much interest, also due to the low environmental effect of production. However, hybrid grape wine composition and varietal differences between interspecific hybrids have not been well defined, particularly for the simple phenols profile. The dynamic of these phenols in wines, where the glycosylated forms can be transformed into the free ones during winemaking, also raises an increasing health interest by their role as antoxidants in wine consumers. In this work an on-line SPE clean-up device, to reduce matrix interference, was combined with ultra-high liquid chromatography-high resolution mass spectrometry in order to increase understanding of the phenolic composition of hybrid grape varieties. Specifically, the phenolic composition of 4 hybrid grape varieties (red, Cabernet Cantor and Prior; white, Muscaris and Solaris) and 2 European grape varieties (red, Merlot; white, Chardonnay) was investigated, focusing on free and glycosidically bound simple phenols and considering compound distribution in pulp, skin, seeds and wine. Using a targeted approach 53 free simple phenols and 7 glycosidic precursors were quantified with quantification limits ranging from 0.001 to 2mgKg -1 and calibration R 2 of 0.99 for over 86% of compounds. The untargeted approach made it possible to tentatively identify 79 glycosylated precursors of selected free simple phenols in the form of -hexoside (N=30), -pentoside (21), -hexoside-hexoside (17), -hexoside-pentoside (4), -pentoside-hexoside (5) and -pentoside-pentoside (2) derivatives on the basis of accurate mass, isotopic pattern and MS/MS fragmentation. Copyright © 2017 Elsevier Ltd. All rights reserved.

  3. Recent trends in application of multivariate curve resolution approaches for improving gas chromatography-mass spectrometry analysis of essential oils.

    Science.gov (United States)

    Jalali-Heravi, Mehdi; Parastar, Hadi

    2011-08-15

    Essential oils (EOs) are valuable natural products that are popular nowadays in the world due to their effects on the health conditions of human beings and their role in preventing and curing diseases. In addition, EOs have a broad range of applications in foods, perfumes, cosmetics and human nutrition. Among different techniques for analysis of EOs, gas chromatography-mass spectrometry (GC-MS) is the most important one in recent years. However, there are some fundamental problems in GC-MS analysis including baseline drift, spectral background, noise, low S/N (signal to noise) ratio, changes in the peak shapes and co-elution. Multivariate curve resolution (MCR) approaches cope with ongoing challenges and are able to handle these problems. This review focuses on the application of MCR techniques for improving GC-MS analysis of EOs published between January 2000 and December 2010. In the first part, the importance of EOs in human life and their relevance in analytical chemistry is discussed. In the second part, an insight into some basics needed to understand prospects and limitations of the MCR techniques are given. In the third part, the significance of the combination of the MCR approaches with GC-MS analysis of EOs is highlighted. Furthermore, the commonly used algorithms for preprocessing, chemical rank determination, local rank analysis and multivariate resolution in the field of EOs analysis are reviewed. Copyright © 2011 Elsevier B.V. All rights reserved.

  4. A Rational Approach for Discovering and Validating Cancer Markers in Very Small Samples Using Mass Spectrometry and ELISA Microarrays

    Directory of Open Access Journals (Sweden)

    Richard C. Zangar

    2004-01-01

    Full Text Available Identifying useful markers of cancer can be problematic due to limited amounts of sample. Some samples such as nipple aspirate fluid (NAF or early-stage tumors are inherently small. Other samples such as serum are collected in larger volumes but archives of these samples are very valuable and only small amounts of each sample may be available for a single study. Also, given the diverse nature of cancer and the inherent variability in individual protein levels, it seems likely that the best approach to screen for cancer will be to determine the profile of a battery of proteins. As a result, a major challenge in identifying protein markers of disease is the ability to screen many proteins using very small amounts of sample. In this review, we outline some technological advances in proteomics that greatly advance this capability. Specifically, we propose a strategy for identifying markers of breast cancer in NAF that utilizes mass spectrometry (MS to simultaneously screen hundreds or thousands of proteins in each sample. The best potential markers identified by the MS analysis can then be extensively characterized using an ELISA microarray assay. Because the microarray analysis is quantitative and large numbers of samples can be efficiently analyzed, this approach offers the ability to rapidly assess a battery of selected proteins in a manner that is directly relevant to traditional clinical assays.

  5. A problem-solving approach to effective insulin injection for patients at either end of the body mass index.

    Science.gov (United States)

    Juip, Micki; Fitzner, Karen

    2012-06-01

    People with diabetes require skills and knowledge to adhere to medication regimens and self-manage this complex disease. Effective self-management is contingent upon effective problem solving and decision making. Gaps existed regarding useful approaches to problem solving by individuals with very low and very high body mass index (BMI) who self-administer insulin injections. This article addresses those gaps by presenting findings from a patient survey, a symposium on the topic of problem solving, and recent interviews with diabetes educators to facilitate problem-solving approaches for people with diabetes with high and low BMI who inject insulin and/or other medications. In practice, problem solving involves problem identification, definition, and specification; goal and barrier identification are a prelude to generating a set of potential strategies for problem resolution and applying these strategies to implement a solution. Teaching techniques, such as site rotation and ensuring that people with diabetes use the appropriate equipment, increase confidence with medication adherence. Medication taking is more effective when people with diabetes are equipped with the knowledge, skills, and problem-solving behaviors to effectively self-manage their injections.

  6. An Alternative Humans to Mars Approach: Reducing Mission Mass with Multiple Mars Flyby Trajectories and Minimal Capability Investments

    Science.gov (United States)

    Whitley, Ryan J.; Jedrey, Richard; Landau, Damon; Ocampo, Cesar

    2015-01-01

    Mars flyby trajectories and Earth return trajectories have the potential to enable lower- cost and sustainable human exploration of Mars. Flyby and return trajectories are true minimum energy paths with low to zero post-Earth departure maneuvers. By emplacing the large crew vehicles required for human transit on these paths, the total fuel cost can be reduced. The traditional full-up repeating Earth-Mars-Earth cycler concept requires significant infrastructure, but a Mars only flyby approach minimizes mission mass and maximizes opportunities to build-up missions in a stepwise manner. In this paper multiple strategies for sending a crew of 4 to Mars orbit and back are examined. With pre-emplaced assets in Mars orbit, a transit habitat and a minimally functional Mars taxi, a complete Mars mission can be accomplished in 3 SLS launches and 2 Mars Flyby's, including Orion. While some years are better than others, ample opportunities exist within a given 15-year Earth-Mars alignment cycle. Building up a mission cadence over time, this approach can translate to Mars surface access. Risk reduction, which is always a concern for human missions, is mitigated by the use of flybys with Earth return (some of which are true free returns) capability.

  7. Identification of Serum Biomarkers for Biliary Tract Cancers by a Proteomic Approach Based on Time-of-Flight Mass Spectrometry

    International Nuclear Information System (INIS)

    Wang, Wen-Jing; Xu, Wang-Hong; Liu, Cha-Zhen; Rashid, Asif; Cheng, Jia-Rong; Liao, Ping; Hu, Heng; Chu, Lisa W.; Gao, Yu-Tang; Yu, Kai; Hsing, Ann W.

    2010-01-01

    Biliary tract cancers (BTCs) are lethal malignancies currently lacking satisfactory methods for early detection and accurate diagnosis. Surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF-MS) is a promising diagnostic tool for this disease. In this pilot study, sera samples from 50 BTCs and 30 cholelithiasis patients as well as 30 healthy subjects from a population-based case-control study were randomly grouped into training set (30 BTCs, 20 cholelithiasis and 20 controls), duplicate of training set, and blind set (20 BTCs, 10 cholelithiasis and 10 controls); all sets were analyzed on Immobilized Metal Affinity Capture ProteinChips via SELDI-TOF-MS. A decision tree classifier was built using the training set and applied to all test sets. The classification tree constructed with the 3,400, 4,502, 5,680, 7,598, and 11,242 mass-to-charge ratio (m/z) protein peaks had a sensitivity of 96.7% and a specificity of 85.0% when comparing BTCs with non-cancers. When applied to the duplicate set, sensitivity was 66.7% and specificity was 70.0%, while in the blind set, sensitivity was 95.0% and specificity was 75.0%. Positive predictive values of the training, duplicate, and blind sets were 82.9%, 62.5% and 79.2%, respectively. The agreement of the training and duplicate sets was 71.4% (Kappa = 0.43, u = 3.98, P < 0.01). The coefficient of variations based on 10 replicates of one sample for the five differential peaks were 15.8–68.8% for intensity and 0–0.05% for m/z. These pilot results suggest that serum protein profiling by SELDI-TOF-MS may be a promising approach for identifying BTCs but low assay reproducibility may limit its application in clinical practice

  8. MALDI-ISD Mass Spectrometry Analysis of Hemoglobin Variants: a Top-Down Approach to the Characterization of Hemoglobinopathies

    Science.gov (United States)

    Théberge, Roger; Dikler, Sergei; Heckendorf, Christian; Chui, David H. K.; Costello, Catherine E.; McComb, Mark E.

    2015-08-01

    Hemoglobinopathies are the most common inherited disorders in humans and are thus the target of screening programs worldwide. Over the past decade, mass spectrometry (MS) has gained a more important role as a clinical means to diagnose variants, and a number of approaches have been proposed for characterization. Here we investigate the use of matrix-assisted laser desorption/ionization time-of-flight MS (MALDI-TOF MS) with sequencing using in-source decay (MALDI-ISD) for the characterization of Hb variants. We explored the effect of matrix selection using super DHB or 1,5-diaminonaphthalene on ISD fragment ion yield and distribution. MALDI-ISD MS of whole blood using super DHB simultaneously provided molecular weights for the alpha and beta chains, as well as extensive fragmentation in the form of sequence defining c-, (z + 2)-, and y-ion series. We observed sequence coverage on the first 70 amino acids positions from the N- and C-termini of the alpha and beta chains in a single experiment. An abundant beta chain N-terminal fragment ion corresponding to βc34 was determined to be a diagnostic marker ion for Hb S (β6 Glu→Val, sickle cell), Hb C (β6 Glu→Lys), and potentially for Hb E (β26 Glu→Lys). The MALDI-ISD analysis of Hb S and HbSC yielded mass shifts corresponding to the variants, demonstrating the potential for high-throughput screening. Characterization of an alpha chain variant, Hb Westmead (α122 His→Gln), generated fragments that established the location of the variant. This study is the first clinical application of MALDI-ISD MS for the determination and characterization of hemoglobin variants.

  9. Surface analysis of lipids by mass spectrometry: more than just imaging.

    Science.gov (United States)

    Ellis, Shane R; Brown, Simon H; In Het Panhuis, Marc; Blanksby, Stephen J; Mitchell, Todd W

    2013-10-01

    Mass spectrometry is now an indispensable tool for lipid analysis and is arguably the driving force in the renaissance of lipid research. In its various forms, mass spectrometry is uniquely capable of resolving the extensive compositional and structural diversity of lipids in biological systems. Furthermore, it provides the ability to accurately quantify molecular-level changes in lipid populations associated with changes in metabolism and environment; bringing lipid science to the "omics" age. The recent explosion of mass spectrometry-based surface analysis techniques is fuelling further expansion of the lipidomics field. This is evidenced by the numerous papers published on the subject of mass spectrometric imaging of lipids in recent years. While imaging mass spectrometry provides new and exciting possibilities, it is but one of the many opportunities direct surface analysis offers the lipid researcher. In this review we describe the current state-of-the-art in the direct surface analysis of lipids with a focus on tissue sections, intact cells and thin-layer chromatography substrates. The suitability of these different approaches towards analysis of the major lipid classes along with their current and potential applications in the field of lipid analysis are evaluated. Copyright © 2013 Elsevier Ltd. All rights reserved.

  10. A genome-wide approach accounting for body mass index identifies genetic variants influencing fasting glycemic traits and insulin resistance

    Science.gov (United States)

    Manning, Alisa K.; Hivert, Marie-France; Scott, Robert A.; Grimsby, Jonna L.; Bouatia-Naji, Nabila; Chen, Han; Rybin, Denis; Liu, Ching-Ti; Bielak, Lawrence F.; Prokopenko, Inga; Amin, Najaf; Barnes, Daniel; Cadby, Gemma; Hottenga, Jouke-Jan; Ingelsson, Erik; Jackson, Anne U.; Johnson, Toby; Kanoni, Stavroula; Ladenvall, Claes; Lagou, Vasiliki; Lahti, Jari; Lecoeur, Cecile; Liu, Yongmei; Martinez-Larrad, Maria Teresa; Montasser, May E.; Navarro, Pau; Perry, John R. B.; Rasmussen-Torvik, Laura J.; Salo, Perttu; Sattar, Naveed; Shungin, Dmitry; Strawbridge, Rona J.; Tanaka, Toshiko; van Duijn, Cornelia M.; An, Ping; de Andrade, Mariza; Andrews, Jeanette S.; Aspelund, Thor; Atalay, Mustafa; Aulchenko, Yurii; Balkau, Beverley; Bandinelli, Stefania; Beckmann, Jacques S.; Beilby, John P.; Bellis, Claire; Bergman, Richard N.; Blangero, John; Boban, Mladen; Boehnke, Michael; Boerwinkle, Eric; Bonnycastle, Lori L.; Boomsma, Dorret I.; Borecki, Ingrid B.; Böttcher, Yvonne; Bouchard, Claude; Brunner, Eric; Budimir, Danijela; Campbell, Harry; Carlson, Olga; Chines, Peter S.; Clarke, Robert; Collins, Francis S.; Corbatón-Anchuelo, Arturo; Couper, David; de Faire, Ulf; Dedoussis, George V; Deloukas, Panos; Dimitriou, Maria; Egan, Josephine M; Eiriksdottir, Gudny; Erdos, Michael R.; Eriksson, Johan G.; Eury, Elodie; Ferrucci, Luigi; Ford, Ian; Forouhi, Nita G.; Fox, Caroline S; Franzosi, Maria Grazia; Franks, Paul W; Frayling, Timothy M; Froguel, Philippe; Galan, Pilar; de Geus, Eco; Gigante, Bruna; Glazer, Nicole L.; Goel, Anuj; Groop, Leif; Gudnason, Vilmundur; Hallmans, Göran; Hamsten, Anders; Hansson, Ola; Harris, Tamara B.; Hayward, Caroline; Heath, Simon; Hercberg, Serge; Hicks, Andrew A.; Hingorani, Aroon; Hofman, Albert; Hui, Jennie; Hung, Joseph; Jarvelin, Marjo Riitta; Jhun, Min A.; Johnson, Paul C.D.; Jukema, J Wouter; Jula, Antti; Kao, W.H.; Kaprio, Jaakko; Kardia, Sharon L. R.; Keinanen-Kiukaanniemi, Sirkka; Kivimaki, Mika; Kolcic, Ivana; Kovacs, Peter; Kumari, Meena; Kuusisto, Johanna; Kyvik, Kirsten Ohm; Laakso, Markku; Lakka, Timo; Lannfelt, Lars; Lathrop, G Mark; Launer, Lenore J.; Leander, Karin; Li, Guo; Lind, Lars; Lindstrom, Jaana; Lobbens, Stéphane; Loos, Ruth J. F.; Luan, Jian’an; Lyssenko, Valeriya; Mägi, Reedik; Magnusson, Patrik K. E.; Marmot, Michael; Meneton, Pierre; Mohlke, Karen L.; Mooser, Vincent; Morken, Mario A.; Miljkovic, Iva; Narisu, Narisu; O’Connell, Jeff; Ong, Ken K.; Oostra, Ben A.; Palmer, Lyle J.; Palotie, Aarno; Pankow, James S.; Peden, John F.; Pedersen, Nancy L.; Pehlic, Marina; Peltonen, Leena; Penninx, Brenda; Pericic, Marijana; Perola, Markus; Perusse, Louis; Peyser, Patricia A; Polasek, Ozren; Pramstaller, Peter P.; Province, Michael A.; Räikkönen, Katri; Rauramaa, Rainer; Rehnberg, Emil; Rice, Ken; Rotter, Jerome I.; Rudan, Igor; Ruokonen, Aimo; Saaristo, Timo; Sabater-Lleal, Maria; Salomaa, Veikko; Savage, David B.; Saxena, Richa; Schwarz, Peter; Seedorf, Udo; Sennblad, Bengt; Serrano-Rios, Manuel; Shuldiner, Alan R.; Sijbrands, Eric J.G.; Siscovick, David S.; Smit, Johannes H.; Small, Kerrin S.; Smith, Nicholas L.; Smith, Albert Vernon; Stančáková, Alena; Stirrups, Kathleen; Stumvoll, Michael; Sun, Yan V.; Swift, Amy J.; Tönjes, Anke; Tuomilehto, Jaakko; Trompet, Stella; Uitterlinden, Andre G.; Uusitupa, Matti; Vikström, Max; Vitart, Veronique; Vohl, Marie-Claude; Voight, Benjamin F.; Vollenweider, Peter; Waeber, Gerard; Waterworth, Dawn M; Watkins, Hugh; Wheeler, Eleanor; Widen, Elisabeth; Wild, Sarah H.; Willems, Sara M.; Willemsen, Gonneke; Wilson, James F.; Witteman, Jacqueline C.M.; Wright, Alan F.; Yaghootkar, Hanieh; Zelenika, Diana; Zemunik, Tatijana; Zgaga, Lina; Wareham, Nicholas J.; McCarthy, Mark I.; Barroso, Ines; Watanabe, Richard M.; Florez, Jose C.; Dupuis, Josée; Meigs, James B.; Langenberg, Claudia

    2013-01-01

    Recent genome-wide association studies have described many loci implicated in type 2 diabetes (T2D) pathophysiology and beta-cell dysfunction, but contributed little to our understanding of the genetic basis of insulin resistance. We hypothesized that genes implicated in insulin resistance pathways may be uncovered by accounting for differences in body mass index (BMI) and potential interaction between BMI and genetic variants. We applied a novel joint meta-analytical approach to test associations with fasting insulin (FI) and glucose (FG) on a genome-wide scale. We present six previously unknown FI loci at P<5×10−8 in combined discovery and follow-up analyses of 52 studies comprising up to 96,496non-diabetic individuals. Risk variants were associated with higher triglyceride and lower HDL cholesterol levels, suggestive of a role for these FI loci in insulin resistance pathways. The localization of these additional loci will aid further characterization of the role of insulin resistance in T2D pathophysiology. PMID:22581228

  11. Identification of clinically relevant Corynebacterium strains by Api Coryne, MALDI-TOF-mass spectrometry and molecular approaches.

    Science.gov (United States)

    Alibi, S; Ferjani, A; Gaillot, O; Marzouk, M; Courcol, R; Boukadida, J

    2015-09-01

    We evaluated the Bruker Biotyper matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) mass spectrometry (MS) for the identification of 97 Corynebacterium clinical in comparison to identification strains by Api Coryne and MALDI-TOF-MS using 16S rRNA gene and hypervariable region of rpoB genes sequencing as a reference method. C. striatum was the predominant species isolated followed by C. amycolatum. There was an agreement between Api Coryne strips and MALDI-TOF-MS identification in 88.65% of cases. MALDI-TOF-MS was unable to differentiate C. aurimucosum from C. minutissimum and C. minutissimum from C. singulare but reliably identify 92 of 97 (94.84%) strains. Two strains remained incompletely identified to the species level by MALDI-TOF-MS and molecular approaches. They belonged to Cellulomonas and Pseudoclavibacter genus. In conclusion, MALDI-TOF-MS is a rapid and reliable method for the identification of Corynebacterium species. However, some limits have been noted and have to be resolved by the application of molecular methods. Copyright © 2015. Published by Elsevier SAS.

  12. A novel approach to quantifying the sensitivity of current and future cosmological datasets to the neutrino mass ordering through Bayesian hierarchical modeling

    Science.gov (United States)

    Gerbino, Martina; Lattanzi, Massimiliano; Mena, Olga; Freese, Katherine

    2017-12-01

    We present a novel approach to derive constraints on neutrino masses, as well as on other cosmological parameters, from cosmological data, while taking into account our ignorance of the neutrino mass ordering. We derive constraints from a combination of current as well as future cosmological datasets on the total neutrino mass Mν and on the mass fractions fν,i =mi /Mν (where the index i = 1 , 2 , 3 indicates the three mass eigenstates) carried by each of the mass eigenstates mi, after marginalizing over the (unknown) neutrino mass ordering, either normal ordering (NH) or inverted ordering (IH). The bounds on all the cosmological parameters, including those on the total neutrino mass, take therefore into account the uncertainty related to our ignorance of the mass hierarchy that is actually realized in nature. This novel approach is carried out in the framework of Bayesian analysis of a typical hierarchical problem, where the distribution of the parameters of the model depends on further parameters, the hyperparameters. In this context, the choice of the neutrino mass ordering is modeled via the discrete hyperparameterhtype, which we introduce in the usual Markov chain analysis. The preference from cosmological data for either the NH or the IH scenarios is then simply encoded in the posterior distribution of the hyperparameter itself. Current cosmic microwave background (CMB) measurements assign equal odds to the two hierarchies, and are thus unable to distinguish between them. However, after the addition of baryon acoustic oscillation (BAO) measurements, a weak preference for the normal hierarchical scenario appears, with odds of 4 : 3 from Planck temperature and large-scale polarization in combination with BAO (3 : 2 if small-scale polarization is also included). Concerning next-generation cosmological experiments, forecasts suggest that the combination of upcoming CMB (COrE) and BAO surveys (DESI) may determine the neutrino mass hierarchy at a high statistical

  13. A comprehensive high-resolution mass spectrometry approach for characterization of metabolites by combination of ambient ionization, chromatography and imaging methods.

    Science.gov (United States)

    Berisha, Arton; Dold, Sebastian; Guenther, Sabine; Desbenoit, Nicolas; Takats, Zoltan; Spengler, Bernhard; Römpp, Andreas

    2014-08-30

    An ideal method for bioanalytical applications would deliver spatially resolved quantitative information in real time and without sample preparation. In reality these requirements can typically not be met by a single analytical technique. Therefore, we combine different mass spectrometry approaches: chromatographic separation, ambient ionization and imaging techniques, in order to obtain comprehensive information about metabolites in complex biological samples. Samples were analyzed by laser desorption followed by electrospray ionization (LD-ESI) as an ambient ionization technique, by matrix-assisted laser desorption/ionization (MALDI) mass spectrometry imaging for spatial distribution analysis and by high-performance liquid chromatography/electrospray ionization mass spectrometry (HPLC/ESI-MS) for quantitation and validation of compound identification. All MS data were acquired with high mass resolution and accurate mass (using orbital trapping and ion cyclotron resonance mass spectrometers). Grape berries were analyzed and evaluated in detail, whereas wheat seeds and mouse brain tissue were analyzed in proof-of-concept experiments. In situ measurements by LD-ESI without any sample preparation allowed for fast screening of plant metabolites on the grape surface. MALDI imaging of grape cross sections at 20 µm pixel size revealed the detailed distribution of metabolites which were in accordance with their biological function. HPLC/ESI-MS was used to quantify 13 anthocyanin species as well as to separate and identify isomeric compounds. A total of 41 metabolites (amino acids, carbohydrates, anthocyanins) were identified with all three approaches. Mass accuracy for all MS measurements was better than 2 ppm (root mean square error). The combined approach provides fast screening capabilities, spatial distribution information and the possibility to quantify metabolites. Accurate mass measurements proved to be critical in order to reliably combine data from different MS

  14. Implications of elevated CO2 on pelagic carbon fluxes in an Arctic mesocosm study – an elemental mass balance approach

    Directory of Open Access Journals (Sweden)

    J. Czerny

    2013-05-01

    Full Text Available Recent studies on the impacts of ocean acidification on pelagic communities have identified changes in carbon to nutrient dynamics with related shifts in elemental stoichiometry. In principle, mesocosm experiments provide the opportunity of determining temporal dynamics of all relevant carbon and nutrient pools and, thus, calculating elemental budgets. In practice, attempts to budget mesocosm enclosures are often hampered by uncertainties in some of the measured pools and fluxes, in particular due to uncertainties in constraining air–sea gas exchange, particle sinking, and wall growth. In an Arctic mesocosm study on ocean acidification applying KOSMOS (Kiel Off-Shore Mesocosms for future Ocean Simulation, all relevant element pools and fluxes of carbon, nitrogen and phosphorus were measured, using an improved experimental design intended to narrow down the mentioned uncertainties. Water-column concentrations of particulate and dissolved organic and inorganic matter were determined daily. New approaches for quantitative estimates of material sinking to the bottom of the mesocosms and gas exchange in 48 h temporal resolution as well as estimates of wall growth were developed to close the gaps in element budgets. However, losses elements from the budgets into a sum of insufficiently determined pools were detected, and are principally unavoidable in mesocosm investigation. The comparison of variability patterns of all single measured datasets revealed analytic precision to be the main issue in determination of budgets. Uncertainties in dissolved organic carbon (DOC, nitrogen (DON and particulate organic phosphorus (POP were much higher than the summed error in determination of the same elements in all other pools. With estimates provided for all other major elemental pools, mass balance calculations could be used to infer the temporal development of DOC, DON and POP pools. Future elevated pCO2 was found to enhance net autotrophic community carbon

  15. Mass spectrometry by means of tandem accelerators

    International Nuclear Information System (INIS)

    Tuniz, C.

    1985-01-01

    Mass spectrometry based on an accelerator allows to measure rare cosmogenic isotopes found in natural samples with isotopic abundances up to 10E-15. The XTU Tandem of Legnaro National Laboratories can measure mean heavy isotopes (36Cl, 41Ca, 129I) in applications interesting cosmochronology and Medicine. The TTT-3 Tandem of the Naples University has been modified in view of precision studies of C14 in Archeology, Paleantology and Geology. In this paper a review is made of principles and methodologies and of some applicationy in the framework of the National Program for mass spectrametry research with the aid of accelerators

  16. Design of pulsed perforated-plate columns for industrial scale mass transfer applications - present experience and the need for a model based approach

    International Nuclear Information System (INIS)

    Roy, Amitava

    2010-01-01

    Mass transfer is a vital unit operation in the processing of spent nuclear fuel in the backend of closed fuel cycle and Pulsed perforated plate extraction columns are used as mass transfer device for more than five decades. The pulsed perforated plate column is an agitated differential contactor, which has wide applicability due to its simplicity, high mass transfer efficiency, high through put, suitability for maintenance free remote operation, ease of cleaning/decontamination and cost effectiveness. Design of pulsed columns are based on a model proposed to describe the hydrodynamics and mass transfer. In equilibrium stage model, the HETS values are obtained from pilot plant experiments and then scaled empirically to design columns for industrial application. The dispersion model accounts for mass transfer kinetics and back-mixing. The drop population balance model can describe complex hydrodynamics of dispersed phase, that is, drop formation, break-up and drop-to-drop interactions. In recent years, significant progress has been made to model pulsed columns using CFD, which provides complete mathematical description of hydrodynamics in terms of spatial distribution of flow fields and 3D visualization. Under the condition of pulsation, the poly-dispersed nature of turbulent droplet swarm renders modeling difficult. In the absence of industry acceptance of proposed models, the conventional chemical engineering practice is to use HETS-NTS concept or HTU-NTU approach to design extraction columns. The practicability of HTU-NTU approach has some limitations due to the lack of experimental data on individual film mass transfer coefficients. Presently, the HETS-NTS concept has been used for designing the columns, which has given satisfactory performance. The design objective is mainly to arrive at the diameter and height of the mass transfer section for a specific plate geometry, fluid properties and pulsing condition to meet the intended throughput (capacity) and mass

  17. qcML : an exchange format for quality control metrics from mass spectrometry experiments

    NARCIS (Netherlands)

    Walzer, Mathias; Pernas, Lucia Espona; Nasso, Sara; Bittremieux, Wout; Nahnsen, Sven; Kelchtermans, Pieter; Pichler, Peter; van den Toorn, Henk W P|info:eu-repo/dai/nl/31093205X; Staes, An; Vandenbussche, Jonathan; Mazanek, Michael; Taus, Thomas; Scheltema, Richard A; Kelstrup, Christian D; Gatto, Laurent; van Breukelen, Bas|info:eu-repo/dai/nl/244219087; Aiche, Stephan; Valkenborg, Dirk; Laukens, Kris; Lilley, Kathryn S; Olsen, Jesper V; Heck, Albert J R|info:eu-repo/dai/nl/105189332; Mechtler, Karl; Aebersold, Ruedi; Gevaert, Kris; Vizcaíno, Juan Antonio; Hermjakob, Henning; Kohlbacher, Oliver; Martens, Lennart

    Quality control is increasingly recognized as a crucial aspect of mass spectrometry based proteomics. Several recent papers discuss relevant parameters for quality control and present applications to extract these from the instrumental raw data. What has been missing, however, is a standard data

  18. Mass-Spectrometry Based Structure Identification of "Known-Unknowns" Using the EPA's CompTox Dashboard (ACS Spring National Meeting) 4 of 7

    Science.gov (United States)

    The CompTox Dashboard is a publicly accessible database provided by the National Center for Computational Toxicology at the US-EPA. The dashboard provides access to a database containing ~720,000 chemicals and integrates a number of our public-facing projects (e.g. ToxCast and Ex...

  19. Investigation of the Antifatigue Effects of Korean Ginseng on Professional Athletes by Gas Chromatography-Time-of-Flight-Mass Spectrometry-Based Metabolomics.

    Science.gov (United States)

    Yan, Bei; Liu, Yao; Shi, Aixin; Wang, Zhihong; Aa, Jiye; Huang, Xiaoping; Liu, Yi

    2018-05-01

    Ginseng is usually used for alleviating fatigue. The purpose of this paper was to evaluate the regulatory effect of Korean ginseng on the metabolic pattern in professional athletes, and, further, to explore the underlying mechanism of the antifatigue effect of Korean ginseng. GC-time-of-flight-MS was used to profile serum samples from professional athletes before training and after 15 and 30 day training, and professional athletes administered with Korean ginseng in the meanwhile. Biochemical parameters of all athletes were also analyzed. For the athlete control group, strength-endurance training resulted in an elevation of creatine kinase (CK) and blood urea nitrogen (BUN), and a reduction in blood hemoglobin, and a dynamic trajectory of the metabolomic profile which were related to fatigue. Korean ginseng treatment not only lead to a marked reduction in CK and blood urea nitrogen (BUN) in serum, but also showed regulatory effects on the serum metabolic profile and restored scores plots close to normal, suggesting that the change in metabolic profiling could reflect the antifatigue effect of Korean ginseng. Furthermore, perturbed levels of 11 endogenous metabolites were regulated by Korean ginseng significantly, which might be primarily involved in lipid metabolism, energy balance, and chemical signaling. These findings suggest that metabolomics is a potential tool for the evaluation of the antifatigue effect of Korean ginseng and for the elucidation of its pharmacological mechanism.

  20. A sensitive and simple ultra-high-performance-liquid chromatography-tandem mass spectrometry based method for the quantification of D-amino acids in body fluids

    NARCIS (Netherlands)

    Visser, Wouter F; Verhoeven-Duif, Nanda M; Ophoff, Roel; Bakker, Steven; Klomp, Leo W; Berger, Ruud; de Koning, Tom J

    2011-01-01

    D-Amino acids are increasingly being recognized as important signaling molecules in mammals, including humans. D-Serine and D-aspartate are believed to act as signaling molecules in the central nervous system. Interestingly, several other D-amino acids also occur in human plasma, but very little is

  1. Deciphering of the Human Interferon-Regulated Proteome by Mass Spectrometry-Based Quantitative Analysis Reveals Extent and Dynamics of Protein Induction and Repression.

    Science.gov (United States)

    Megger, Dominik A; Philipp, Jos; Le-Trilling, Vu Thuy Khanh; Sitek, Barbara; Trilling, Mirko

    2017-01-01

    Interferons (IFNs) are pleotropic cytokines secreted upon encounter of pathogens and tumors. Applying their antipathogenic, antiproliferative, and immune stimulatory capacities, recombinant IFNs are frequently prescribed as drugs to treat different diseases. IFNs act by changing the gene expression profile of cells. Due to characteristics such as rapid gene induction and signaling, IFNs also represent prototypical model systems for various aspects of biomedical research (e.g., signal transduction). In regard to the signaling and activated promoters, IFNs can be subdivided into two groups. Here, alterations of the cellular proteome of human cells treated with IFNα and IFNγ were elucidated in a time-resolved manner by quantitative proteome analysis. The majority of protein regulations were strongly IFN type and time dependent. In addition to the expected upregulation of IFN-responsive proteins, an astonishing number of proteins became profoundly repressed especially by IFNγ. Thus, our comprehensive analysis revealed important insights into the human IFN-regulated proteome and its dynamics of protein induction and repression. Interestingly, the new class of IFN-repressed genes comprises known host factors for highly relevant pathogens such as HIV, dengue virus, and hepatitis C virus.

  2. Deciphering of the Human Interferon-Regulated Proteome by Mass Spectrometry-Based Quantitative Analysis Reveals Extent and Dynamics of Protein Induction and Repression

    Directory of Open Access Journals (Sweden)

    Dominik A. Megger

    2017-09-01

    Full Text Available Interferons (IFNs are pleotropic cytokines secreted upon encounter of pathogens and tumors. Applying their antipathogenic, antiproliferative, and immune stimulatory capacities, recombinant IFNs are frequently prescribed as drugs to treat different diseases. IFNs act by changing the gene expression profile of cells. Due to characteristics such as rapid gene induction and signaling, IFNs also represent prototypical model systems for various aspects of biomedical research (e.g., signal transduction. In regard to the signaling and activated promoters, IFNs can be subdivided into two groups. Here, alterations of the cellular proteome of human cells treated with IFNα and IFNγ were elucidated in a time-resolved manner by quantitative proteome analysis. The majority of protein regulations were strongly IFN type and time dependent. In addition to the expected upregulation of IFN-responsive proteins, an astonishing number of proteins became profoundly repressed especially by IFNγ. Thus, our comprehensive analysis revealed important insights into the human IFN-regulated proteome and its dynamics of protein induction and repression. Interestingly, the new class of IFN-repressed genes comprises known host factors for highly relevant pathogens such as HIV, dengue virus, and hepatitis C virus.

  3. Epitope mapping of salmonella flagellar hook-associated protein, FlgK, with mass spectrometry-based immuno-capture proteomics using chicken (gallus gallus domesticus] sera

    Science.gov (United States)

    Salmonella, a Gram-negative rod, is the leading foodborne pathogen associated with human acute bacterial gastroenteritis worldwide. The Salmonella flagellum is responsible for bacterial movement, colonization and invasion in the host gastrointestinal tract. The flagellum has a complex structure, c...

  4. Analysis of drugs of forensic interest with capillary zone electrophoresis/time-of-flight mass spectrometry based on the use of non-volatile buffers

    Czech Academy of Sciences Publication Activity Database

    Gottardo, R.; Mikšík, Ivan; Aturki, Z.; Sorio, D.; Seri, C.; Fanali, S.; Tagliaro, F.

    2012-01-01

    Roč. 33, č. 4 (2012), s. 599-606 ISSN 0173-0835 R&D Projects: GA ČR(CZ) GA203/08/1428 Institutional research plan: CEZ:AV0Z50110509 Keywords : capillary electrophoresis * drugs of abuse * non-volatile buffer * CE-MS Subject RIV: CB - Analytical Chemistry, Separation Impact factor: 3.261, year: 2012

  5. Rapid detection of atrazine and metolachlor in farm soils: gas chromatography-mass spectrometry-based analysis using the bubble-in-drop single drop microextraction enrichment method.

    Science.gov (United States)

    Williams, D Bradley G; George, Mosotho J; Marjanovic, Ljiljana

    2014-08-06

    Tracking of metolachlor and atrazine herbicides in agricultural soils, from spraying through to harvest, was conducted using our recently reported "bubble-in-drop single-drop microextraction" method. The method showed good linearity (R(2) = 0.999 and 0.999) in the concentration range of 0.01-1.0 ng/mL with LOD values of 0.01 and 0.02 ng/mL for atrazine and metolachlor, respectively. Sonication methods were poor at releasing these herbicides from the soil matrixes, while hot water extraction readily liberated them, providing an efficient accessible alternative to sonication techniques. Good recoveries of 97% and 105% were shown for atrazine and metolachlor, respectively, from the soil. The spiking protocol was also investigated, resulting in a traceless spiking method. We demonstrate a very sensitive technique by which to assess, for example, the length of residence of pesticides in given soils and thus risk of exposure.

  6. Development and validation of a mass spectrometry-based assay for quantification of insulin-like factor 3 in human serum

    DEFF Research Database (Denmark)

    Albrethsen, Jakob; Frederiksen, Hanne; Andersson, Anna-Maria

    2018-01-01

    BACKGROUND: The circulating level of the peptide hormone insulin-like factor 3 (INSL3) is a promising diagnostic marker reflecting Leydig cell function in the male. Few commercial immunoassays of varying quality exist. Therefore, we decided to develop and validate a precise method for quantificat......BACKGROUND: The circulating level of the peptide hormone insulin-like factor 3 (INSL3) is a promising diagnostic marker reflecting Leydig cell function in the male. Few commercial immunoassays of varying quality exist. Therefore, we decided to develop and validate a precise method...

  7. Some mass measurement problems

    International Nuclear Information System (INIS)

    Merritt, J.S.

    1976-01-01

    Concerning the problem of determining the thickness of a target, an uncomplicated approach is to measure its mass and area and take the quotient. This paper examines the mass measurement aspect of such an approach. (author)

  8. Combined effects of Mass and Velocity on forward displacement and phenomenological ratings: a functional measurement approach to the Momentum metaphor

    Directory of Open Access Journals (Sweden)

    Michel-Ange Amorim

    2010-01-01

    Full Text Available Representational Momentum (RepMo refers to the phenomenon that the vanishing position of a moving target is perceived as displaced ahead in the direction of movement. Originally taken to reflect a strict internalization of physical momentum, the finding that the target implied mass did not have an effect led to its subsequent reinterpretation as a second-order isomorphism between mental representations and principles of the physical world. However, very few studies have addressed the effects of mass on RepMo, and consistent replications of the null effect are lacking. The extent of motor engagement of the observers in RepMo tasks has, on the other hand, been suggested to determine the occurrence of the phenomenon; however, no systematic investigations were made of the degree to which it might modulate the effect of target mass. In the present work, we use Information Integration Theory to study the joint effects of different motor responses, target velocity and target mass on RepMo, and also of velocity and target mass on rating responses. Outcomes point not only to an effect of mass on RepMo, as to a differential effect of response modality on kinematic (e.g., velocity and dynamic (e.g., mass variables. Comparisons of patterns of mislocalisation with phenomenological ratings suggest that simplification of physical principles, rather than strict internalization or isomorphism per se, might underlie RepMo.

  9. A Proteomic Approach for Identification of Bacteria Using Tandem Mass Spectrometry Combined With a Translatome Database and Statistical Scoring

    National Research Council Canada - National Science Library

    Dworzanski, Jacek P; Snyder, A. P; Zhang, Haiyan; Wishart, David; Chen, Rui; Li, Liang

    2005-01-01

    ... mass spectra against a database translated from fully sequenced bacterial genomes. An in-house developed algorithm for filtering of search results have been tested with Bacillus subtilis and Escherichia coli microorganism...

  10. Sequence protein identification by randomized sequence database and transcriptome mass spectrometry (SPIDER-TMS): from manual to automatic application of a 'de novo sequencing' approach.

    Science.gov (United States)

    Pascale, Raffaella; Grossi, Gerarda; Cruciani, Gabriele; Mecca, Giansalvatore; Santoro, Donatello; Sarli Calace, Renzo; Falabella, Patrizia; Bianco, Giuliana

    Sequence protein identification by a randomized sequence database and transcriptome mass spectrometry software package has been developed at the University of Basilicata in Potenza (Italy) and designed to facilitate the determination of the amino acid sequence of a peptide as well as an unequivocal identification of proteins in a high-throughput manner with enormous advantages of time, economical resource and expertise. The software package is a valid tool for the automation of a de novo sequencing approach, overcoming the main limits and a versatile platform useful in the proteomic field for an unequivocal identification of proteins, starting from tandem mass spectrometry data. The strength of this software is that it is a user-friendly and non-statistical approach, so protein identification can be considered unambiguous.

  11. Profiling monoterpenol glycoconjugation in Vitis vinifera L. cv. Muscat of Alexandria using a novel putative compound database approach, high resolution mass spectrometry and collision induced dissociation fragmentation analysis.

    Science.gov (United States)

    Hjelmeland, Anna K; Zweigenbaum, Jerry; Ebeler, Susan E

    2015-08-05

    In this work we present a novel approach for the identification of plant metabolites using ultrahigh performance liquid chromatography coupled to accurate mass time-of-flight mass spectrometry. The workflow involves developing an in-house compound database consisting of exact masses of previously identified as well as putative compounds. The database is used to screen accurate mass spectrometry (MS) data to identify possible compound matches. Subsequent tandem MS data is acquired for possible matches and used for structural elucidation. The methodology is applied to profile monoterpene glycosides in Vitis vinifera cv. Muscat of Alexandria grape berries over three developmental stages. Monoterpenes are a subclass of terpenes, the largest class of plant secondary metabolites, and are found in two major forms in the plant, "bound" to one or more sugar moieties or "free" of said sugar moieties. In the free form, monoterpenes are noted for their fragrance and play important roles in plant defense and as attractants for pollinators. However, glycoconjugation renders these compounds odorless, and it is this form that the plant uses for monoterpene storage. In order to gain insight into monoterpene biochemistry and their fate in the plant an analysis of intact glycosides is essential. Eighteen monoterpene glycosides were identified including a monoterpene trisaccharide glycoside, which is tentatively identified here for this first time in any plant. Additionally, while previous studies have identified monoterpene malonylated glucosides in other grapevine tissue, we tentatively identify them for the first time in grape berries. This analytical approach can be readily applied to other plants and the workflow approach can also be used for other classes of compounds. This approach, in general, provides researchers with data to support the identification of putative compounds, which is especially useful when no standard is available. Copyright © 2015 Elsevier B.V. All rights

  12. Phenomenological approach to the modelling of elliptical galaxies: The problem of the mass-to-light ratio

    Directory of Open Access Journals (Sweden)

    Samurović S.

    2007-01-01

    Full Text Available In this paper the problem of the phenomenological modelling of elliptical galaxies using various available observational data is presented. Recently, Tortora, Cardona and Piedipalumbo (2007 suggested a double power law expression for the global cumulative mass-to-light ratio of elliptical galaxies. We tested their expression on a sample of ellipticals for which we have the estimates of the mass-to-light ratio beyond ~ 3 effective radii, a region where dark matter is expected to play an important dynamical role. We found that, for all the galaxies in our sample, we have α + β > 0, but that this does not necessarily mean a high dark matter content. The galaxies with higher mass (and higher dark matter content also have higher value of α+β. It was also shown that there is an indication that the galaxies with higher value of the effective radius also have higher dark matter content. .

  13. A novel approach to quantifying the sensitivity of current and future cosmological datasets to the neutrino mass ordering through Bayesian hierarchical modeling

    Directory of Open Access Journals (Sweden)

    Martina Gerbino

    2017-12-01

    Full Text Available We present a novel approach to derive constraints on neutrino masses, as well as on other cosmological parameters, from cosmological data, while taking into account our ignorance of the neutrino mass ordering. We derive constraints from a combination of current as well as future cosmological datasets on the total neutrino mass Mν and on the mass fractions fν,i=mi/Mν (where the index i=1,2,3 indicates the three mass eigenstates carried by each of the mass eigenstates mi, after marginalizing over the (unknown neutrino mass ordering, either normal ordering (NH or inverted ordering (IH. The bounds on all the cosmological parameters, including those on the total neutrino mass, take therefore into account the uncertainty related to our ignorance of the mass hierarchy that is actually realized in nature. This novel approach is carried out in the framework of Bayesian analysis of a typical hierarchical problem, where the distribution of the parameters of the model depends on further parameters, the hyperparameters. In this context, the choice of the neutrino mass ordering is modeled via the discrete hyperparameter htype, which we introduce in the usual Markov chain analysis. The preference from cosmological data for either the NH or the IH scenarios is then simply encoded in the posterior distribution of the hyperparameter itself. Current cosmic microwave background (CMB measurements assign equal odds to the two hierarchies, and are thus unable to distinguish between them. However, after the addition of baryon acoustic oscillation (BAO measurements, a weak preference for the normal hierarchical scenario appears, with odds of 4:3 from Planck temperature and large-scale polarization in combination with BAO (3:2 if small-scale polarization is also included. Concerning next-generation cosmological experiments, forecasts suggest that the combination of upcoming CMB (COrE and BAO surveys (DESI may determine the neutrino mass hierarchy at a high

  14. Next generation offline approaches to trace organic compound speciation: Approaching comprehensive speciation with soft ionization and very high resolution tandem mass spectrometry

    Science.gov (United States)

    Khare, P.; Marcotte, A.; Sheu, R.; Ditto, J.; Gentner, D. R.

    2017-12-01

    Intermediate- and semi-volatile organic compounds (IVOCs and SVOCs) have high secondary organic aerosol (SOA) yields, as well as significant ozone formation potentials. Yet, their emission sources and oxidation pathways remain largely understudied due to limitations in current analytical capabilities. Online mass spectrometers are able to collect real time data but their limited mass resolving power renders molecular level characterization of IVOCs and SVOCs from the unresolved complex mixture unfeasible. With proper sampling techniques and powerful analytical instrumentation, our offline tandem mass spectrometry (i.e. MS×MS) techniques provide molecular-level and structural identification over wide polarity and volatility ranges. We have designed a novel analytical system for offline analysis of gas-phase SOA precursors collected on custom-made multi-bed adsorbent tubes. Samples are desorbed into helium via a gradual temperature ramp and sample flow is split equally for direct-MS×MS analysis and separation via gas chromatography (GC). The effluent from GC separation is split again for analysis via atmospheric pressure chemical ionization quadrupole time-of-flight mass spectrometry (APCI-Q×TOF) and traditional electron ionization mass spectrometry (EI-MS). The compounds for direct-MS×MS analysis are delivered via a transfer line maintained at 70ºC directly to APCI-Q×TOF, thus preserving the molecular integrity of thermally-labile, or other highly-reactive, organic compounds. Both our GC-MS×MS and direct-MS×MS analyses report high accuracy parent ion masses as well as information on molecular structure via MS×MS, which together increase the resolution of unidentified complex mixtures. We demonstrate instrument performance and present preliminary results from urban atmospheric samples collected from New York City with a wide range of compounds including highly-functionalized organic compounds previously understudied in outdoor air. Our work offers new

  15. Payload Mass Identification of a Single-Link Flexible Arm Moving under Gravity: An Algebraic Identification Approach

    Directory of Open Access Journals (Sweden)

    Juan Carlos Cambera

    2015-01-01

    Full Text Available We deal with the online identification of the payload mass carried by a single-link flexible arm that moves on a vertical plane and therefore is affected by the gravity force. Specifically, we follow a frequency domain design methodology to develop an algebraic identifier. This identifier is capable of achieving robust and efficient mass estimates even in the presence of sensor noise. In order to highlight its performance, the proposed estimator is experimentally tested and compared with other classical methods in several situations that resemble the most typical operation of a manipulator.

  16. Effect of Astringent Stimuli on Salivary Protein Interactions Elucidated by Complementary Proteomics Approaches.

    Science.gov (United States)

    Delius, Judith; Médard, Guillaume; Kuster, Bernhard; Hofmann, Thomas

    2017-03-15

    The interaction of astringent substances with salivary proteins, which results in protein precipitation, is considered a key event in the molecular mechanism underlying the oral sensation of puckering astringency. As the chemical nature of orally active astringents is diverse and the knowledge of their interactions with salivary proteins rather fragmentary, human whole saliva samples were incubated with suprathreshold and isointensity solutions of the astringent polyphenol (-)-epigallocatechin gallate, the multivalent metal salt iron(III) sulfate, the amino-functionalized polysaccharide chitosan, and the basic protein lysozyme. After separation of the precipitated proteins, the proteins affected by the astringents were identified and relatively quantified for the first time by complementary bottom-up and top-down mass spectrometry-based proteomics approaches. Major salivary target proteins, which may be involved in astringency perception, are reported here for each astringent stimulus.

  17. Integrative Approaches for the Identification and Localization of Specialized Metabolites in Tripterygium Roots1[OPEN

    Science.gov (United States)

    Fischedick, Justin T.; Lange, Malte F.; Poirier, Brenton C.

    2017-01-01

    Members of the genus Tripterygium are known to contain an astonishing diversity of specialized metabolites. The lack of authentic standards has been an impediment to the rapid identification of such metabolites in extracts. We employed an approach that involves the searching of multiple, complementary chromatographic and spectroscopic data sets against the Spektraris database to speed up the metabolite identification process. Mass spectrometry-based imaging indicated a differential localization of triterpenoids to the periderm and sesquiterpene alkaloids to the cortex layer of Tripterygium roots. We further provide evidence that triterpenoids are accumulated to high levels in cells that contain suberized cell walls, which might indicate a mechanism for storage. To our knowledge, our data provide first insights into the cell type specificity of metabolite accumulation in Tripterygium and set the stage for furthering our understanding of the biological implications of specialized metabolites in this genus. PMID:27864443

  18. Large-scale retrospective evaluation of regulated liquid chromatography-mass spectrometry bioanalysis projects using different total error approaches.

    Science.gov (United States)

    Tan, Aimin; Saffaj, Taoufiq; Musuku, Adrien; Awaiye, Kayode; Ihssane, Bouchaib; Jhilal, Fayçal; Sosse, Saad Alaoui; Trabelsi, Fethi

    2015-03-01

    The current approach in regulated LC-MS bioanalysis, which evaluates the precision and trueness of an assay separately, has long been criticized for inadequate balancing of lab-customer risks. Accordingly, different total error approaches have been proposed. The aims of this research were to evaluate the aforementioned risks in reality and the difference among four common total error approaches (β-expectation, β-content, uncertainty, and risk profile) through retrospective analysis of regulated LC-MS projects. Twenty-eight projects (14 validations and 14 productions) were randomly selected from two GLP bioanalytical laboratories, which represent a wide variety of assays. The results show that the risk of accepting unacceptable batches did exist with the current approach (9% and 4% of the evaluated QC levels failed for validation and production, respectively). The fact that the risk was not wide-spread was only because the precision and bias of modern LC-MS assays are usually much better than the minimum regulatory requirements. Despite minor differences in magnitude, very similar accuracy profiles and/or conclusions were obtained from the four different total error approaches. High correlation was even observed in the width of bias intervals. For example, the mean width of SFSTP's β-expectation is 1.10-fold (CV=7.6%) of that of Saffaj-Ihssane's uncertainty approach, while the latter is 1.13-fold (CV=6.0%) of that of Hoffman-Kringle's β-content approach. To conclude, the risk of accepting unacceptable batches was real with the current approach, suggesting that total error approaches should be used instead. Moreover, any of the four total error approaches may be used because of their overall similarity. Lastly, the difficulties/obstacles associated with the application of total error approaches in routine analysis and their desirable future improvements are discussed. Copyright © 2015 Elsevier B.V. All rights reserved.

  19. Modelling the surface mass balance of the Greenland ice sheet and neighbouring ice caps : A dynamical and statistical downscaling approach

    NARCIS (Netherlands)

    Noël, B.P.Y.

    2018-01-01

    The Greenland ice sheet (GrIS) is the world’s second largest ice mass, storing about one tenth of the Earth’s freshwater. If totally melted, global sea level would rise by 7.4 m, affecting low-lying regions worldwide. Since the mid-1990s, increased atmospheric and oceanic temperatures have

  20. Heat and mass exchange within the soil - plant canopy-atmosphere system : a theroretical approach and its validation

    NARCIS (Netherlands)

    El-Kilani, R.M.M.

    1997-01-01

    Heat, mass and momentum transfer between the canopy air layer and the layer of air above has a very intermittent nature. This intermittent nature is due to the passage at the canopy top of coherent structures which have a length scale at least as large as the canopy height. The periodic

  1. Desorption atmospheric pressure photoionization high-resolution mass spectrometry: a complementary approach for the chemical analysis of atmospheric aerosols

    Czech Academy of Sciences Publication Activity Database

    Parshintsev, J.; Vaikkinen, A.; Lipponen, K.; Vrkoslav, Vladimír; Cvačka, Josef; Kostiainen, R.; Kotiaho, T.; Hartonen, K.; Riekkola, M. L.; Kauppila, T. J.

    2015-01-01

    Roč. 29, č. 13 (2015), s. 1233-1241 ISSN 0951-4198 Grant - others:GA AV ČR(CZ) M200551204 Institutional support: RVO:61388963 Keywords : atmospheric aerosols * mass spectrometry * ambient ionization Subject RIV: CB - Analytical Chemistry , Separation Impact factor: 2.226, year: 2015

  2. A New Approach to Determine the Density of Liquids and Solids without Measuring Mass and Volume: Introducing the "Solidensimeter"

    Science.gov (United States)

    Kiriktas, Halit; Sahin, Mehmet; Eslek, Sinan; Kiriktas, Irem

    2018-01-01

    This study aims to design a mechanism with which the density of any solid or liquid can be determined without measuring its mass and volume in order to help students comprehend the concept of density more easily. The "solidensimeter" comprises of two scaled and nested glass containers (graduated cylinder or beaker) and sufficient water.…

  3. Pep2Path: automated mass spectrometry-guided genome mining of peptidic natural products.

    Directory of Open Access Journals (Sweden)

    Marnix H Medema

    2014-09-01

    Full Text Available Nonribosomally and ribosomally synthesized bioactive peptides constitute a source of molecules of great biomedical importance, including antibiotics such as penicillin, immunosuppressants such as cyclosporine, and cytostatics such as bleomycin. Recently, an innovative mass-spectrometry-based strategy, peptidogenomics, has been pioneered to effectively mine microbial strains for novel peptidic metabolites. Even though mass-spectrometric peptide detection can be performed quite fast, true high-throughput natural product discovery approaches have still been limited by the inability to rapidly match the identified tandem mass spectra to the gene clusters responsible for the biosynthesis of the corresponding compounds. With Pep2Path, we introduce a software package to fully automate the peptidogenomics approach through the rapid Bayesian probabilistic matching of mass spectra to their corresponding biosynthetic gene clusters. Detailed benchmarking of the method shows that the approach is powerful enough to correctly identify gene clusters even in data sets that consist of hundreds of genomes, which also makes it possible to match compounds from unsequenced organisms to closely related biosynthetic gene clusters in other genomes. Applying Pep2Path to a data set of compounds without known biosynthesis routes, we were able to identify candidate gene clusters for the biosynthesis of five important compounds. Notably, one of these clusters was detected in a genome from a different subphylum of Proteobacteria than that in which the molecule had first been identified. All in all, our approach paves the way towards high-throughput discovery of novel peptidic natural products. Pep2Path is freely available from http://pep2path.sourceforge.net/, implemented in Python, licensed under the GNU General Public License v3 and supported on MS Windows, Linux and Mac OS X.

  4. Identification of urinary biomarkers of exposure to di-(2-propylheptyl) phthalate using high-resolution mass spectrometry and two data-screening approaches.

    Science.gov (United States)

    Shih, Chia-Lung; Liao, Pao-Mei; Hsu, Jen-Yi; Chung, Yi-Ning; Zgoda, Victor G; Liao, Pao-Chi

    2018-02-01

    Di-(2-propylheptyl) phthalate (DPHP) is a plasticizer used in polyvinyl chloride and vinyl chloride copolymer that has been suggested to be a toxicant in rats and may affect human health. Because the use of DPHP is increasing, the general German population is being exposed to DPHP. Toxicant metabolism is important for human toxicant exposure assessments. To date, the knowledge regarding DPHP metabolism has been limited, and only four metabolites have been identified in human urine. Ultra-performance liquid chromatography was coupled with Orbitrap high-resolution mass spectrometry (MS) and two data-screening approaches-the signal mining algorithm with isotope tracing (SMAIT) and the mass defect filter (MDF)-for DPHP metabolite candidate discovery. In total, 13 and 104 metabolite candidates were identified by the two approaches, respectively, in in vitro DPHP incubation samples. Of these candidates, 17 were validated as tentative exposure biomarkers using a rat model, 13 of which have not been reported in the literature. The two approaches generated rather different tentative DPHP exposure biomarkers, indicating that these approaches are complementary for discovering exposure biomarkers. Compared with the four previously reported DPHP metabolites, the three tentative novel biomarkers had higher peak intensity ratios, and two were confirmed as DPHP hydroxyl metabolites based on their MS/MS product ion profiles. These three tentative novel biomarkers should be further investigated for potential application in human exposure assessment. Copyright © 2017 Elsevier Ltd. All rights reserved.

  5. Sequential injection approach for simultaneous determination of ultratrace plutonium and neptunium in urine with accelerator mass spectrometry

    DEFF Research Database (Denmark)

    Qiao, Jixin; Hou, Xiaolin; Roos, Per

    2013-01-01

    An analytical method was developed for simultaneous determination of ultratrace level plutonium (Pu) and neptunium (Np) using iron hydroxide coprecipitation in combination with automated sequential injection extraction chromatography separation and accelerator mass spectrometry (AMS) measurement...... show that preboiling and aging are important for obtaining high chemical yields for both Pu and Np, which is possibly related to the aggregation and adsorption behavior of organic substances contained in urine. Although the optimal condition for Np and Pu simultaneous determination requires 5-day aging...

  6. Desorption atmospheric pressure photoionization high-resolution mass spectrometry: a complementary approach for the chemical analysis of atmospheric aerosols.

    Science.gov (United States)

    Parshintsev, Jevgeni; Vaikkinen, Anu; Lipponen, Katriina; Vrkoslav, Vladimir; Cvačka, Josef; Kostiainen, Risto; Kotiaho, Tapio; Hartonen, Kari; Riekkola, Marja-Liisa; Kauppila, Tiina J

    2015-07-15

    On-line chemical characterization methods of atmospheric aerosols are essential to increase our understanding of physicochemical processes in the atmosphere, and to study biosphere-atmosphere interactions. Several techniques, including aerosol mass spectrometry, are nowadays available, but they all suffer from some disadvantages. In this research, desorption atmospheric pressure photoionization high-resolution (Orbitrap) mass spectrometry (DAPPI-HRMS) is introduced as a complementary technique for the fast analysis of aerosol chemical composition without the need for sample preparation. Atmospheric aerosols from city air were collected on a filter, desorbed in a DAPPI source with a hot stream of toluene and nitrogen, and ionized using a vacuum ultraviolet lamp at atmospheric pressure. To study the applicability of the technique for ambient aerosol analysis, several samples were collected onto filters and analyzed, with the focus being on selected organic acids. To compare the DAPPI-HRMS data with results obtained by an established method, each filter sample was divided into two equal parts, and the second half of the filter was extracted and analyzed by liquid chromatography/mass spectrometry (LC/MS). The DAPPI results agreed with the measured aerosol particle number. In addition to the targeted acids, the LC/MS and DAPPI-HRMS methods were found to detect different compounds, thus providing complementary information about the aerosol samples. DAPPI-HRMS showed several important oxidation products of terpenes, and numerous compounds were tentatively identified. Thanks to the soft ionization, high mass resolution, fast analysis, simplicity and on-line applicability, the proposed methodology has high potential in the field of atmospheric research. Copyright © 2015 John Wiley & Sons, Ltd.

  7. New approach to the determination phosphorothioate oligonucleotides by ultra high performance liquid chromatography coupled with inductively coupled plasma mass spectrometry.

    Science.gov (United States)

    Studzińska, Sylwia; Mounicou, Sandra; Szpunar, Joanna; Łobiński, Ryszard; Buszewski, Bogusław

    2015-01-15

    This text presents a novel method for the separation and detection of phosphorothioate oligonucleotides with the use of ion pair ultra high performance liquid chromatography coupled with inductively coupled plasma mass spectrometry The research showed that hexafluoroisopropanol/triethylamine based mobile phases may be successfully used when liquid chromatography is coupled with such elemental detection. However, the concentration of both HFIP and TEA influences the final result. The lower concentration of HFIP, the lower the background in ICP-MS and the greater the sensitivity. The method applied for the analysis of serum samples was based on high resolution inductively coupled plasma mass spectrometry. Utilization of this method allows determination of fifty times lower quantity of phosphorothioate oligonucleotides than in the case of quadrupole mass analyzer. Monitoring of (31)P may be used to quantify these compounds at the level of 80 μg L(-1), while simultaneous determination of sulfur is very useful for qualitative analysis. Moreover, the results presented in this paper demonstrate the practical applicability of coupling LC with ICP-MS in determining phosphorothioate oligonucleotides and their metabolites in serum within 7 min with a very good sensitivity. The method was linear in the concentration range between 0.2 and 3 mg L(-1). The limit of detection was in the range of 0.07 and 0.13 mg L(-1). Accuracy varied with concentration, but was in the range of 3%. Copyright © 2014 Elsevier B.V. All rights reserved.

  8. A new approach to determine the density of liquids and solids without measuring mass and volume: introducing the solidensimeter

    Science.gov (United States)

    Kiriktaş, Halit; Şahin, Mehmet; Eslek, Sinan; Kiriktaş, İrem

    2018-05-01

    This study aims to design a mechanism with which the density of any solid or liquid can be determined without measuring its mass and volume in order to help students comprehend the concept of density more easily. The solidensimeter comprises of two scaled and nested glass containers (graduated cylinder or beaker) and sufficient water. In this method, the density measurement was made using the Archimedes’ principle stating that an object fully submerged in a liquid displaces the same amount of liquid as its volume, while an object partially submerged or floating displaces the same amount of liquid as its mass. Using this method, the density of any solids or liquids can be determined using a simple mathematical ratio. At the end of the process a mechanism that helps students to comprehend the density topic more easily was designed. The system is easy-to-design, uses low-cost equipment and enables one to determine the density of any solid or liquid without measuring its mass and volume.

  9. Regioisomers of octanoic acid-containing structured triacylglycerols analyzed by tandem mass spectrometry using ammonia negative ion chemical ionization

    DEFF Research Database (Denmark)

    Kurvinen, J.P.; Mu, Huiling; Kallio, H.

    2001-01-01

    Tandem mass spectrometry based on ammonia negative ion chemical ionization and sample introduction via direct exposure probe was applied to analysis of regioisomeric structures of octanoic acid containing structured triacylglycerols (TAG) of type MML, MLM, MLL, and LML (M, medium-chain fatty acid...

  10. A semi-automated approach to derive elevation time-series and calculate glacier mass balance from historical aerial imagery

    Science.gov (United States)

    Whorton, E.; Headman, A.; Shean, D. E.; McCann, E.

    2017-12-01

    Understanding the implications of glacier recession on water resources in the western U.S. requires quantifying glacier mass change across large regions over several decades. Very few glaciers in North America have long-term continuous field measurements of glacier mass balance. However, systematic aerial photography campaigns began in 1957 on many glaciers in the western U.S. and Alaska. These historical, vertical aerial stereo-photographs documenting glacier evolution have recently become publically available. Digital elevation models (DEM) of the transient glacier surface preserved in each imagery timestamp can be derived, then differenced to calculate glacier volume and mass change to improve regional geodetic solutions of glacier mass balance. In order to batch process these data, we use Python-based algorithms and Agisoft Photoscan structure from motion (SfM) photogrammetry software to semi-automate DEM creation, and orthorectify and co-register historical aerial imagery in a high-performance computing environment. Scanned photographs are rotated to reduce scaling issues, cropped to the same size to remove fiducials, and batch histogram equalization is applied to improve image quality and aid pixel-matching algorithms using the Python library OpenCV. Processed photographs are then passed to Photoscan through the Photoscan Python library to create DEMs and orthoimagery. To extend the period of record, the elevation products are co-registered to each other, airborne LiDAR data, and DEMs derived from sub-meter commercial satellite imagery. With the exception of the placement of ground control points, the process is entirely automated with Python. Current research is focused on: one, applying these algorithms to create geodetic mass balance time series for the 90 photographed glaciers in Washington State and two, evaluating the minimal amount of positional information required in Photoscan to prevent distortion effects that cannot be addressed during co

  11. Mass carbon monoxide poisoning at an ice-hockey game: initial approach and long-term follow-up.

    Science.gov (United States)

    Mortelmans, Luc J M; Populaire, Jacques; Desruelles, Didier; Sabbe, Marc B

    2013-12-01

    A mass carbon monoxide (CO) intoxication during an ice-hockey game is described. Two hundred and thirty-five patients were seen in different hospitals, 88 of them the same night at the nearby emergency department. To evaluate long-term implications and to identify relevant indicators, a follow-up study was organized 1 year after the incident. Apart from the file data from the emergency departments, a 1-year follow-up mailing was sent to all patients. One hundred and ninety-one patients returned their questionnaire (86%). The mean age of the patients was 28 years, with 61% men. The mean carboxyhaemoglobin (COHb) was 9.9%. COHb levels were significantly higher for individuals on the ice (referee, players and maintenance personnel). There was a significant relationship with the initial presence of dizziness, fatigue and the COHb level. Headache, abdominal pain, nausea and vomiting were not significantly related to the COHb levels. The relationship between symptoms and CO level, however, should be interpreted with caution as there was a wide range between exposure and blood tests. 5.2% of patients had residual complaints, all including headache, with a significant higher incidence with high COHb levels. Only two patients had an abnormal neurological control (one slightly disturbed electroencephalography and one persistent encephalopathic complaint). Work incapacity was also significantly related to COHb levels. CO mass poisonings remain a risk in indoor sporting events. Although it causes an acute mass casualty incident, it is limited in time and delayed problems are scarce. Symptomatology is a poor tool for triage. The best prevention is the use of nonmineral energy sources such as for example electricity.

  12. A new approach to develop computer-aided diagnosis scheme of breast mass classification using deep learning technology.

    Science.gov (United States)

    Qiu, Yuchen; Yan, Shiju; Gundreddy, Rohith Reddy; Wang, Yunzhi; Cheng, Samuel; Liu, Hong; Zheng, Bin

    2017-01-01

    To develop and test a deep learning based computer-aided diagnosis (CAD) scheme of mammograms for classifying between malignant and benign masses. An image dataset involving 560 regions of interest (ROIs) extracted from digital mammograms was used. After down-sampling each ROI from 512×512 to 64×64 pixel size, we applied an 8 layer deep learning network that involves 3 pairs of convolution-max-pooling layers for automatic feature extraction and a multiple layer perceptron (MLP) classifier for feature categorization to process ROIs. The 3 pairs of convolution layers contain 20, 10, and 5 feature maps, respectively. Each convolution layer is connected with a max-pooling layer to improve the feature robustness. The output of the sixth layer is fully connected with a MLP classifier, which is composed of one hidden layer and one logistic regression layer. The network then generates a classification score to predict the likelihood of ROI depicting a malignant mass. A four-fold cross validation method was applied to train and test this deep learning network. The results revealed that this CAD scheme yields an area under the receiver operation characteristic curve (AUC) of 0.696±0.044, 0.802±0.037, 0.836±0.036, and 0.822±0.035 for fold 1 to 4 testing datasets, respectively. The overall AUC of the entire dataset is 0.790±0.019. This study demonstrates the feasibility of applying a deep learning based CAD scheme to classify between malignant and benign breast masses without a lesion segmentation, image feature computation and selection process.

  13. A New Approach to Develop Computer-aided Diagnosis Scheme of Breast Mass Classification Using Deep Learning Technology

    Science.gov (United States)

    Qiu, Yuchen; Yan, Shiju; Gundreddy, Rohith Reddy; Wang, Yunzhi; Cheng, Samuel; Liu, Hong; Zheng, Bin

    2017-01-01

    PURPOSE To develop and test a deep learning based computer-aided diagnosis (CAD) scheme of mammograms for classifying between malignant and benign masses. METHODS An image dataset involving 560 regions of interest (ROIs) extracted from digital mammograms was used. After down-sampling each ROI from 512×512 to 64×64 pixel size, we applied an 8 layer deep learning network that involves 3 pairs of convolution-max-pooling layers for automatic feature extraction and a multiple layer perceptron (MLP) classifier for feature categorization to process ROIs. The 3 pairs of convolution layers contain 20, 10, and 5 feature maps, respectively. Each convolution layer is connected with a max-pooling layer to improve the feature robustness. The output of the sixth layer is fully connected with a MLP classifier, which is composed of one hidden layer and one logistic regression layer. The network then generates a classification score to predict the likelihood of ROI depicting a malignant mass. A four-fold cross validation method was applied to train and test this deep learning network. RESULTS The results revealed that this CAD scheme yields an area under the receiver operation characteristic curve (AUC) of 0.696±0.044, 0.802±0.037, 0.836±0.036, and 0.822±0.035 for fold 1 to 4 testing datasets, respectively. The overall AUC of the entire dataset is 0.790±0.019. CONCLUSIONS This study demonstrates the feasibility of applying a deep learning based CAD scheme to classify between malignant and benign breast masses without a lesion segmentation, image feature computation and selection process. PMID:28436410

  14. Development of a new certified reference material of diosgenin using mass balance approach and Coulometric titration method.

    Science.gov (United States)

    Gong, Ningbo; Zhang, Baoxi; Hu, Fan; Du, Hui; Du, Guanhua; Gao, Zhaolin; Lu, Yang

    2014-12-01

    Certified reference materials (CRMs) can be used as a valuable tool to validate the trueness of measurement methods and to establish metrological traceability of analytical results. Diosgenin has been selected as a candidate reference material. Characterization of the material relied on two different methods, mass balance method and Coulometric titration method (CT). The certified value of diosgenin CRM is 99.80% with an expanded uncertainty of 0.37% (k=2). The new CRM of diosgenin can be used to validate analytical methods, improve the accuracy of measurement data and control the quality of diosgenin in relevant pharmaceutical formulations. Copyright © 2014 Elsevier Inc. All rights reserved.

  15. MOOC Design – Dissemination to the Masses or Facilitation of Social Learning and a Deep Approach to Learning?

    DEFF Research Database (Denmark)

    Christensen, Inger-Marie F.; Dam Laursen, Mette; Bøggild, Jacob

    2016-01-01

    This article accounts for the design of the massive open online course (MOOC) Hans Christian Andersen’s Fairy tales on FutureLearn and reports on the effectiveness of this design in terms of engaging learners in social learning and encouraging a deep approach to learning. A learning pathway...... and increased educator feedback. Course data show that that some learners use the space provided for social interaction and mutual support. A learning pathway that engages learners in discussion and progression from week to week facilitates a deep approach to learning. However, this requires more support from...

  16. Approaching the CDF Top Quark Mass Legacy Measurement in the Lepton+Jets channel with the Matrix Element Method

    Energy Technology Data Exchange (ETDEWEB)

    Tosciri, Cecilia [Univ. of Pisa (Italy)

    2016-01-01

    The discovery of the bottom quark in 1977 at the Tevatron Collider triggered the search for its partner in the third fermion isospin doublet, the top quark, which was discovered 18 years later in 1995 by the CDF and D=0 experiments during the Tevatron Run I. By 1990, intensive efforts by many groups at several accelerators had lifted to over 90 GeV=c2 the lower mass limit, such that since then the Tevatron became the only accelerator with high-enough energy to possibly discover this amazingly massive quark. After its discovery, the determination of top quark properties has been one of the main goals of the Fermilab Tevatron Collider, and more recently also of the Large Hadron Collider (LHC) at CERN. Since the mass value plays an important role in a large number of theoretical calculations on fundamental processes, improving the accuracy of its measurement has been at any time a goal of utmost importance. The present thesis describes in detail the contributions given by the candidate to the massive preparation work needed to make the new analysis possible, during her 8 months long stay at Fermilab.

  17. Research Resource: A Dual Proteomic Approach Identifies Regulated Islet Proteins During β-Cell Mass Expansion In Vivo

    DEFF Research Database (Denmark)

    Horn, Signe; Kirkegaard, Jeannette S.; Hoelper, Soraya

    2016-01-01

    to be up regulated as a response to pregnancy. These included several proteins, not previously associated with pregnancy-induced islet expansion, such as CLIC1, STMN1, MCM6, PPIB, NEDD4, and HLTF. Confirming the validity of our approach, we also identified proteins encoded by genes known to be associated...

  18. An integrated approach for estimating global glacio isostatic adjustment, land ice, hydrology and ocean mass trends within a complete coupled Earth system framework

    Science.gov (United States)

    Schumacher, M.; Bamber, J. L.; Martin, A.

    2016-12-01

    Future sea level rise (SLR) is one of the most serious consequences of climate change. Therefore, understanding the drivers of past sea level change is crucial for improving predictions. SLR integrates many Earth system components including oceans, land ice, terrestrial water storage, as well as solid Earth effects. Traditionally, each component have been tackled separately, which has often lead to inconsistencies between discipline-specific estimates of each part of the sea level budget. To address these issues, the European Research Council has funded a five year project aimed at producing a physically-based, data-driven solution for the complete coupled land-ocean-solid Earth system that is consistent with the full suite of observations, prior knowledge and fundamental geophysical constraints. The project is called "GlobalMass" and based at University of Bristol. Observed mass movement from the GRACE mission plus vertical land motion from a global network of permanent GPS stations will be utilized in a data-driven approach to estimate glacial isostatic adjustment (GIA) without introducing any assumptions about the Earth structure or ice loading history. A Bayesian Hierarchical Model (BHM) will be used as the framework to combine the satellite and in-situ observations alongside prior information that incorporates the physics of the coupled system such as conservation of mass and characteristic length scales of different processes in both space and time. The BHM is used to implement a simultaneous solution at a global scale. It will produce a consistent partitioning of the integrated SLR signal into its steric (thermal) and barystatic (mass) component for the satellite era. The latter component is induced by hydrological mass trends and melting of land ice. The BHM was developed and tested on Antarctica, where it has been used to separate surface, ice dynamic and GIA signals simultaneously. We illustrate the approach and concepts with examples from this test case

  19. Tandem Affinity Purification Approach Coupled to Mass Spectrometry to Identify Post-translational Modifications of Histones Associated with Chromatin-Binding Proteins.

    Science.gov (United States)

    Beyer, Sophie; Robin, Philippe; Ait-Si-Ali, Slimane

    2017-01-01

    Protein purification by tandem affinity purification (TAP)-tag coupled to mass spectrometry analysis is usually used to reveal protein complex composition. Here we describe a TAP-tag purification of chromatin-bound proteins along with associated nucleosomes, which allow exhaustive identification of protein partners. Moreover, this method allows exhaustive identification of the post-translational modifications (PTMs) of the associated histones. Thus, in addition to partner characterization, this approach reveals the associated epigenetic landscape that can shed light on the function and properties of the studied chromatin-bound protein.

  20. Defining Diagnostic Biomarkers Using Shotgun Proteomics and MALDI-TOF Mass Spectrometry.

    Science.gov (United States)

    Armengaud, Jean

    2017-01-01

    Whole-cell MALDI-TOF has become a robust and widely used tool to quickly identify any pathogen. In addition to being routinely used in hospitals, it is also useful for low cost dereplication in large scale screening procedures of new environmental isolates for environmental biotechnology or taxonomical applications. Here, I describe how specific biomarkers can be defined using shotgun proteomics and whole-cell MALDI-TOF mass spectrometry. Based on MALDI-TOF spectra recorded on a given set of pathogens with internal calibrants, m/z values of interest are extracted. The proteins which contribute to these peaks are deduced from label-free shotgun proteomics measurements carried out on the same sample. Quantitative information based on the spectral count approach allows ranking the most probable candidates. Proteogenomic approaches help to define whether these proteins give the same m/z values along the whole taxon under consideration or result in heterogeneous lists. These specific biomarkers nicely complement conventional profiling approaches and may help to better define groups of organisms, for example at the subspecies level.

  1. Analysis of two-phase flow inter-subchannel mass and momentum exchanges by the two-fluid model approach

    Energy Technology Data Exchange (ETDEWEB)

    Ninokata, H. [Tokyo Institute of Technology (Japan); Deguchi, A. [ENO Mathematical Analysis, Tokyo (Japan); Kawahara, A. [Kumamoto Univ., Kumamoto (Japan)

    1995-09-01

    A new void drift model for the subchannel analysis method is presented for the thermohydraulics calculation of two-phase flows in rod bundles where the flow model uses a two-fluid formulation for the conservation of mass, momentum and energy. A void drift model is constructed based on the experimental data obtained in a geometrically simple inter-connected two circular channel test sections using air-water as working fluids. The void drift force is assumed to be an origin of void drift velocity components of the two-phase cross-flow in a gap area between two adjacent rods and to overcome the momentum exchanges at the phase interface and wall-fluid interface. This void drift force is implemented in the cross flow momentum equations. Computational results have been successfully compared to experimental data available including 3x3 rod bundle data.

  2. Mass movements in the Rio Grande Valley (Quebrada de Humahuaca, Northwestern Argentina): a methodological approach to reduce the risk

    Science.gov (United States)

    Marcato, G.; Pasuto, A.; Rivelli, F. R.

    2009-10-01

    Slope processes such as slides and debris flows, are among the main events that induce effects on the Rio Grande sediment transport capacity. The slides mainly affect the slope of the Rio Grande river basin while debris and mud flows phenomena take place in the tributary valleys. In the past decades several mass movements occurred causing victims and great damages to roads and villages and therefore hazard assessment and risk mitigation is of paramount importance for a correct development of the area. This is also an urgent need since the Quebrada de Humahuaca was recently included in the UNESCO World Cultural Heritage. The growing tourism business may lead to an uncontrolled urbanization of the valley with the consequent enlargement of threatened areas. In this framework mitigation measures have to take into acc