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  1. Mass spectrometry identifies multiple organophosphorylated sites on tubulin

    Grigoryan, Hasmik; Schopfer, Lawrence M.; Peeples, Eric S.; Duysen, Ellen G.; Grigoryan, Marine; Thompson, Charles M.; Lockridge, Oksana

    2009-01-01

    Acute toxicity of organophosphorus poisons (OP) is explained by inhibition of acetylcholinesterase in nerve synapses. Low-dose effects are hypothesized to result from modification of other proteins, whose identity is not yet established. The goal of the present work was to obtain information that would make it possible to identify tubulin as a target of OP exposure. Tubulin was selected for study because live mice injected with a nontoxic dose of a biotinylated organophosphorus agent appeared to have OP-labeled tubulin in brain as determined by binding to avidin beads and mass spectrometry. The experiments with live mice were not conclusive because binding to avidin beads could be nonspecific. To be convincing, it is necessary to find and characterize the OP-labeled tubulin peptide. The search for OP-labeled tubulin peptides was begun by identifying residues capable of making a covalent bond with OP. Pure bovine tubulin (0.012 mM) was treated with 0.01-0.5 mM chlorpyrifos oxon for 24 h at 37 o C in pH 8.3 buffer. The identity of labeled amino acids and percent labeling was determined by mass spectrometry. Chlorpyrifos oxon bound covalently to tyrosines 83, 103, 108, 161, 224, 262, 272, 357, and 399 in bovine alpha tubulin, and to tyrosines 50, 51, 59, 106, 159, 281, 310, and 340 in bovine beta tubulin. The most reactive were tyrosine 83 in alpha and tyrosine 281 in beta tubulin. In the presence of 1 mM GTP, percent labeling increased 2-fold. Based on the crystal structure of the tubulin heterodimer (PDB 1jff) tyrosines 83 and 281 are well exposed to solvent. In conclusion seventeen tyrosines in tubulin have the potential to covalently bind chlorpyrifos oxon. These results will be useful when searching for OP-labeled tubulin in live animals.

  2. Identifying the Multiple Intelligences of Your Students

    McClellan, Joyce A.; Conti, Gary J.

    2008-01-01

    One way of addressing individual differences among adult learners is to identify the Multiple Intelligences of the learner. Multiple Intelligences refers to the concept developed by Howard Gardner that challenges the traditional view of intelligence and explains the presence of nine different Multiple Intelligences. The purpose of this study was…

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

    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

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

    Janice M Leung

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

  5. Major roles for minor bacterial lipids identified by mass spectrometry.

    Garrett, Teresa A

    2017-11-01

    Mass spectrometry of lipids, especially those isolated from bacteria, has ballooned over the past two decades, affirming in the process the complexity of the lipidome. With this has come the identification of new and interesting lipid structures. Here is an overview of several novel lipids, from both Gram-negative and Gram-positive bacteria with roles in health and disease, whose structural identification was facilitated using mass spectrometry. This article is part of a Special Issue entitled: Bacterial Lipids edited by Russell E. Bishop. Copyright © 2016 Elsevier B.V. All rights reserved.

  6. Identify multiple myeloma stem cells: Utopia?

    Saltarella, Ilaria; Lamanuzzi, Aurelia; Reale, Antonia; Vacca, Angelo; Ria, Roberto

    2015-01-26

    Multiple myeloma (MM) is a hematologic malignancy of monoclonal plasma cells which remains incurable despite recent advances in therapies. The presence of cancer stem cells (CSCs) has been demonstrated in many solid and hematologic tumors, so the idea of CSCs has been proposed for MM, even if MM CSCs have not been define yet. The existence of myeloma CSCs with clonotypic B and clonotypic non B cells was postulated by many groups. This review aims to focus on these distinct clonotypic subpopulations and on their ability to develop and sustain MM. The bone marrow microenvironment provides to MM CSCs self-renewal, survival and drug resistance thanks to the presence of normal and cancer stem cell niches. The niches and CSCs interact each other through adhesion molecules and the interplay between ligands and receptors activates stemness signaling (Hedgehog, Wnt and Notch pathways). MM CSCs are also supposed to be responsible for drug resistance that happens in three steps from the initial cancer cell homing microenvironment-mediated to development of microenvironment-independent drug resistance. In this review, we will underline all these aspects of MM CSCs.

  7. Identifying modifications in RNA by MALDI mass spectrometry

    Douthwaite, Stephen; Kirpekar, Finn

    2007-01-01

    as RNA modifications added in cell-free in vitro systems. MALDI-MS is particularly useful in cases in which other techniques such as those involving primer extension or chromatographic analyses are not practicable. To date, MALDI-MS has been used to localize rRNA modifications that are involved......Posttranscriptional modifications on the base or sugar of ribonucleosides generally result in mass increases that can be measured by mass spectrometry. Matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) is a direct and accurate means of determining the masses of RNAs. Mass...... spectra produced by MALDI are relatively straightforward to interpret, because they are dominated by singly charged ions, making it possible to analyze complex mixtures of RNA oligonucleotides ranging from trinucleotides up to 20-mers. Analysis of modifications within much longer RNAs, such as ribosomal...

  8. Simulation of multiple scattering background in heavy ion backscattering spectrometry

    Li, M.M.; O'Connor, D.J.

    1999-01-01

    With the development of heavy ion backscattering spectrometry (HIBS) for the detection of trace quantities of heavy-atom impurities on Si surfaces, it is necessary to quantify the multiple scattering contribution to the spectral background. In the present work, the Monte Carlo computer simulation program TRIM has been used to study the backscattering spectrum and the multiple scattering background features for heavy ions C, Ne, Si, Ar and Kr impinging on four types of targets: (1) a single ultra-thin (free standing) Au film of 10 A thickness, (2) a 10 A Au film on a 50 A Si surface, (3) a 10 A Au film on an Si substrate (10 000 A), and (4) a thick target (10 000 A) of pure Si. The ratio of the signal from the Au thin layer to the background due to multiple scattering has been derived by fitting the simulation results. From the simulation results, it is found that the Au film contributes to the background which the Si plays a role in developing due to the ion's multiple scattering in the substrate. Such a background is generated neither by only the Au thin layer nor by the pure Si substrate independently. The corresponding mechanism of multiple scattering in the target can be explained as one large-angle scattering in the Au layer and subsequently several small angle scatterings in the substrate. This study allows an appropriate choice of incident beam species and energy range when the HIBS is utilized to analyse low level impurities in Si wafers

  9. Hierarchical cluster analysis of technical replicates to identify interferents in untargeted mass spectrometry metabolomics.

    Caesar, Lindsay K; Kvalheim, Olav M; Cech, Nadja B

    2018-08-27

    Mass spectral data sets often contain experimental artefacts, and data filtering prior to statistical analysis is crucial to extract reliable information. This is particularly true in untargeted metabolomics analyses, where the analyte(s) of interest are not known a priori. It is often assumed that chemical interferents (i.e. solvent contaminants such as plasticizers) are consistent across samples, and can be removed by background subtraction from blank injections. On the contrary, it is shown here that chemical contaminants may vary in abundance across each injection, potentially leading to their misidentification as relevant sample components. With this metabolomics study, we demonstrate the effectiveness of hierarchical cluster analysis (HCA) of replicate injections (technical replicates) as a methodology to identify chemical interferents and reduce their contaminating contribution to metabolomics models. Pools of metabolites with varying complexity were prepared from the botanical Angelica keiskei Koidzumi and spiked with known metabolites. Each set of pools was analyzed in triplicate and at multiple concentrations using ultraperformance liquid chromatography coupled to mass spectrometry (UPLC-MS). Before filtering, HCA failed to cluster replicates in the data sets. To identify contaminant peaks, we developed a filtering process that evaluated the relative peak area variance of each variable within triplicate injections. These interferent peaks were found across all samples, but did not show consistent peak area from injection to injection, even when evaluating the same chemical sample. This filtering process identified 128 ions that appear to originate from the UPLC-MS system. Data sets collected for a high number of pools with comparatively simple chemical composition were highly influenced by these chemical interferents, as were samples that were analyzed at a low concentration. When chemical interferent masses were removed, technical replicates clustered in

  10. Identifying multiple influential spreaders based on generalized closeness centrality

    Liu, Huan-Li; Ma, Chuang; Xiang, Bing-Bing; Tang, Ming; Zhang, Hai-Feng

    2018-02-01

    To maximize the spreading influence of multiple spreaders in complex networks, one important fact cannot be ignored: the multiple spreaders should be dispersively distributed in networks, which can effectively reduce the redundance of information spreading. For this purpose, we define a generalized closeness centrality (GCC) index by generalizing the closeness centrality index to a set of nodes. The problem converts to how to identify multiple spreaders such that an objective function has the minimal value. By comparing with the K-means clustering algorithm, we find that the optimization problem is very similar to the problem of minimizing the objective function in the K-means method. Therefore, how to find multiple nodes with the highest GCC value can be approximately solved by the K-means method. Two typical transmission dynamics-epidemic spreading process and rumor spreading process are implemented in real networks to verify the good performance of our proposed method.

  11. Robust modal curvature features for identifying multiple damage in beams

    Ostachowicz, Wiesław; Xu, Wei; Bai, Runbo; Radzieński, Maciej; Cao, Maosen

    2014-03-01

    Curvature mode shape is an effective feature for damage detection in beams. However, it is susceptible to measurement noise, easily impairing its advantage of sensitivity to damage. To deal with this deficiency, this study formulates an improved curvature mode shape for multiple damage detection in beams based on integrating a wavelet transform (WT) and a Teager energy operator (TEO). The improved curvature mode shape, termed the WT - TEO curvature mode shape, has inherent capabilities of immunity to noise and sensitivity to damage. The proposed method is experimentally validated by identifying multiple cracks in cantilever steel beams with the mode shapes acquired using a scanning laser vibrometer. The results demonstrate that the improved curvature mode shape can identify multiple damage accurately and reliably, and it is fairly robust to measurement noise.

  12. Identifying multiple influential spreaders by a heuristic clustering algorithm

    Bao, Zhong-Kui [School of Mathematical Science, Anhui University, Hefei 230601 (China); Liu, Jian-Guo [Data Science and Cloud Service Research Center, Shanghai University of Finance and Economics, Shanghai, 200133 (China); Zhang, Hai-Feng, E-mail: haifengzhang1978@gmail.com [School of Mathematical Science, Anhui University, Hefei 230601 (China); Department of Communication Engineering, North University of China, Taiyuan, Shan' xi 030051 (China)

    2017-03-18

    The problem of influence maximization in social networks has attracted much attention. However, traditional centrality indices are suitable for the case where a single spreader is chosen as the spreading source. Many times, spreading process is initiated by simultaneously choosing multiple nodes as the spreading sources. In this situation, choosing the top ranked nodes as multiple spreaders is not an optimal strategy, since the chosen nodes are not sufficiently scattered in networks. Therefore, one ideal situation for multiple spreaders case is that the spreaders themselves are not only influential but also they are dispersively distributed in networks, but it is difficult to meet the two conditions together. In this paper, we propose a heuristic clustering (HC) algorithm based on the similarity index to classify nodes into different clusters, and finally the center nodes in clusters are chosen as the multiple spreaders. HC algorithm not only ensures that the multiple spreaders are dispersively distributed in networks but also avoids the selected nodes to be very “negligible”. Compared with the traditional methods, our experimental results on synthetic and real networks indicate that the performance of HC method on influence maximization is more significant. - Highlights: • A heuristic clustering algorithm is proposed to identify the multiple influential spreaders in complex networks. • The algorithm can not only guarantee the selected spreaders are sufficiently scattered but also avoid to be “insignificant”. • The performance of our algorithm is generally better than other methods, regardless of real networks or synthetic networks.

  13. Identifying multiple influential spreaders by a heuristic clustering algorithm

    Bao, Zhong-Kui; Liu, Jian-Guo; Zhang, Hai-Feng

    2017-01-01

    The problem of influence maximization in social networks has attracted much attention. However, traditional centrality indices are suitable for the case where a single spreader is chosen as the spreading source. Many times, spreading process is initiated by simultaneously choosing multiple nodes as the spreading sources. In this situation, choosing the top ranked nodes as multiple spreaders is not an optimal strategy, since the chosen nodes are not sufficiently scattered in networks. Therefore, one ideal situation for multiple spreaders case is that the spreaders themselves are not only influential but also they are dispersively distributed in networks, but it is difficult to meet the two conditions together. In this paper, we propose a heuristic clustering (HC) algorithm based on the similarity index to classify nodes into different clusters, and finally the center nodes in clusters are chosen as the multiple spreaders. HC algorithm not only ensures that the multiple spreaders are dispersively distributed in networks but also avoids the selected nodes to be very “negligible”. Compared with the traditional methods, our experimental results on synthetic and real networks indicate that the performance of HC method on influence maximization is more significant. - Highlights: • A heuristic clustering algorithm is proposed to identify the multiple influential spreaders in complex networks. • The algorithm can not only guarantee the selected spreaders are sufficiently scattered but also avoid to be “insignificant”. • The performance of our algorithm is generally better than other methods, regardless of real networks or synthetic networks.

  14. Identifying multiple submissions in Internet research: preserving data integrity.

    Bowen, Anne M; Daniel, Candice M; Williams, Mark L; Baird, Grayson L

    2008-11-01

    Internet-based sexuality research with hidden populations has become increasingly popular. Respondent anonymity may encourage participation and lower social desirability, but associated disinhibition may promote multiple submissions, especially when incentives are offered. The goal of this study was to identify the usefulness of different variables for detecting multiple submissions from repeat responders and to explore incentive effects. The data included 1,900 submissions from a three-session Internet intervention with a pretest and three post-test questionnaires. Participants were men who have sex with men and incentives were offered to rural participants for completing each questionnaire. The final number of submissions included 1,273 "unique", 132 first submissions by "repeat responders" and 495 additional submissions by the "repeat responders" (N = 1,900). Four categories of repeat responders were identified: "infrequent" (2-5 submissions), "persistent" (6-10 submissions), "very persistent" (11-30 submissions), and "hackers" (more than 30 submissions). Internet Provider (IP) addresses, user names, and passwords were the most useful for identifying "infrequent" repeat responders. "Hackers" often varied their IP address and identifying information to prevent easy identification, but investigating the data for small variations in IP, using reverse telephone look up, and patterns across usernames and passwords were helpful. Incentives appeared to play a role in stimulating multiple submissions, especially from the more sophisticated "hackers". Finally, the web is ever evolving and it will be necessary to have good programmers and staff who evolve as fast as "hackers".

  15. Identifying Multiple Populations in M71 using CN

    Gerber, Jeffrey M.; Friel, Eileen D.; Vesperini, Enrico

    2018-01-01

    It is now well established that globular clusters (GCs) host multiple stellar populations characterized by differences in several light elements. While these populations have been found in nearly all GCs, we still lack an entirely successful model to explain their formation. A key constraint to these models is the detailed pattern of light element abundances seen among the populations; different techniques for identifying these populations probe different elements and do not always yield the same results. We study a large sample of stars in the GC M71 for light elements C and N, using the CN and CH band strength to identify multiple populations. Our measurements come from low-resolution spectroscopy obtained with the WIYN-3.5m telescope for ~150 stars from the tip of the red-giant branch down to the main-sequence turn-off. The large number of stars and broad spatial coverage of our sample (out to ~3.5 half-light radii) allows us to carry out a comprehensive characterization of the multiple populations in M71. We use a combination of the various spectroscopic and photometric indicators to draw a more complete picture of the properties of the populations and to investigate the consistency of classifications using different techniques.

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

    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.

  17. Chagas disease vector blood meal sources identified by protein mass spectrometry.

    Judith I Keller

    Full Text Available Chagas disease is a complex vector borne parasitic disease involving blood feeding Triatominae (Hemiptera: Reduviidae insects, also known as kissing bugs, and the vertebrates they feed on. This disease has tremendous impacts on millions of people and is a global health problem. The etiological agent of Chagas disease, Trypanosoma cruzi (Kinetoplastea: Trypanosomatida: Trypanosomatidae, is deposited on the mammalian host in the insect's feces during a blood meal, and enters the host's blood stream through mucous membranes or a break in the skin. Identifying the blood meal sources of triatomine vectors is critical in understanding Chagas disease transmission dynamics, can lead to identification of other vertebrates important in the transmission cycle, and aids management decisions. The latter is particularly important as there is little in the way of effective therapeutics for Chagas disease. Several techniques, mostly DNA-based, are available for blood meal identification. However, further methods are needed, particularly when sample conditions lead to low-quality DNA or to assess the risk of human cross-contamination. We demonstrate a proteomics-based approach, using liquid chromatography tandem mass spectrometry (LC-MS/MS to identify host-specific hemoglobin peptides for blood meal identification in mouse blood control samples and apply LC-MS/MS for the first time to Triatoma dimidiata insect vectors, tracing blood sources to species. In contrast to most proteins, hemoglobin, stabilized by iron, is incredibly stable even being preserved through geologic time. We compared blood stored with and without an anticoagulant and examined field-collected insect specimens stored in suboptimal conditions such as at room temperature for long periods of time. To our knowledge, this is the first study using LC-MS/MS on field-collected arthropod disease vectors to identify blood meal composition, and where blood meal identification was confirmed with more

  18. Multivariate two-part statistics for analysis of correlated mass spectrometry data from multiple biological specimens.

    Taylor, Sandra L; Ruhaak, L Renee; Weiss, Robert H; Kelly, Karen; Kim, Kyoungmi

    2017-01-01

    High through-put mass spectrometry (MS) is now being used to profile small molecular compounds across multiple biological sample types from the same subjects with the goal of leveraging information across biospecimens. Multivariate statistical methods that combine information from all biospecimens could be more powerful than the usual univariate analyses. However, missing values are common in MS data and imputation can impact between-biospecimen correlation and multivariate analysis results. We propose two multivariate two-part statistics that accommodate missing values and combine data from all biospecimens to identify differentially regulated compounds. Statistical significance is determined using a multivariate permutation null distribution. Relative to univariate tests, the multivariate procedures detected more significant compounds in three biological datasets. In a simulation study, we showed that multi-biospecimen testing procedures were more powerful than single-biospecimen methods when compounds are differentially regulated in multiple biospecimens but univariate methods can be more powerful if compounds are differentially regulated in only one biospecimen. We provide R functions to implement and illustrate our method as supplementary information CONTACT: sltaylor@ucdavis.eduSupplementary information: 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.

  19. Identifying TF-MiRNA Regulatory Relationships Using Multiple Features.

    Mingyu Shao

    Full Text Available MicroRNAs are known to play important roles in the transcriptional and post-transcriptional regulation of gene expression. While intensive research has been conducted to identify miRNAs and their target genes in various genomes, there is only limited knowledge about how microRNAs are regulated. In this study, we construct a pipeline that can infer the regulatory relationships between transcription factors and microRNAs from ChIP-Seq data with high confidence. In particular, after identifying candidate peaks from ChIP-Seq data, we formulate the inference as a PU learning (learning from only positive and unlabeled examples problem. Multiple features including the statistical significance of the peaks, the location of the peaks, the transcription factor binding site motifs, and the evolutionary conservation are derived from peaks for training and prediction. To further improve the accuracy of our inference, we also apply a mean reciprocal rank (MRR-based method to the candidate peaks. We apply our pipeline to infer TF-miRNA regulatory relationships in mouse embryonic stem cells. The experimental results show that our approach provides very specific findings of TF-miRNA regulatory relationships.

  20. The Protein Identifier Cross-Referencing (PICR service: reconciling protein identifiers across multiple source databases

    Leinonen Rasko

    2007-10-01

    Full Text Available Abstract Background Each major protein database uses its own conventions when assigning protein identifiers. Resolving the various, potentially unstable, identifiers that refer to identical proteins is a major challenge. This is a common problem when attempting to unify datasets that have been annotated with proteins from multiple data sources or querying data providers with one flavour of protein identifiers when the source database uses another. Partial solutions for protein identifier mapping exist but they are limited to specific species or techniques and to a very small number of databases. As a result, we have not found a solution that is generic enough and broad enough in mapping scope to suit our needs. Results We have created the Protein Identifier Cross-Reference (PICR service, a web application that provides interactive and programmatic (SOAP and REST access to a mapping algorithm that uses the UniProt Archive (UniParc as a data warehouse to offer protein cross-references based on 100% sequence identity to proteins from over 70 distinct source databases loaded into UniParc. Mappings can be limited by source database, taxonomic ID and activity status in the source database. Users can copy/paste or upload files containing protein identifiers or sequences in FASTA format to obtain mappings using the interactive interface. Search results can be viewed in simple or detailed HTML tables or downloaded as comma-separated values (CSV or Microsoft Excel (XLS files suitable for use in a local database or a spreadsheet. Alternatively, a SOAP interface is available to integrate PICR functionality in other applications, as is a lightweight REST interface. Conclusion We offer a publicly available service that can interactively map protein identifiers and protein sequences to the majority of commonly used protein databases. Programmatic access is available through a standards-compliant SOAP interface or a lightweight REST interface. The PICR

  1. Identifying the related compounds using electrospray ionization tandem mass spectrometry: bromotyrosine alkaloids from marine sponge Psammaplysilla purpurea

    Tilvi, S.; DeSouza, L.

    electrospray ionization tandem mass spectrometry (ESI-MS/MS). This sponge has tremendous chemical diversity of bromotyrosine alkaloids. Here we have used the proteomics approach in identifying related bromotyrosine alkaloids based on the predicated mass...

  2. Imaging mass spectrometry identifies prognostic ganglioside species in rodent intracranial transplants of glioma and medulloblastoma.

    Leonardo Ermini

    Full Text Available Matrix-assisted laser desorption ionization (MALDI imaging mass spectrometry (MALDI-MSI allows us to investigate the distribution of lipid molecules within tissues. We used MALDI-MSI to identify prognostic gangliosides in tissue sections of rat intracranial allografts of rat glioma and mouse intracranial xenografts of human medulloblastoma. In the healthy adult rodent brain, GM1 and GD1 were the main types of glycolipids. Both gangliosides were absent in both intracranial transplants. The ganglioside GM3 was not present in the healthy adult brain but was highly expressed in rat glioma allografts. In combination with tandem mass spectrometry GM3 (d18:1/C24:0 was identified as the most abundant ganglioside species in the glioma allotransplant. By contrast, mouse xenografts of human medulloblastoma were characterized by prominent expression of the ganglioside GM2 (d18:0/C18:0. Together, these data demonstrate that tissue-based MALDI-MSI of gangliosides is able to discriminate between different brain tumors and may be a useful clinical tool for their classification and grading.

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

    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.

  4. Identifying specific protein interaction partners using quantitative mass spectrometry and bead proteomes

    Trinkle-Mulcahy, Laura; Boulon, Séverine; Lam, Yun Wah; Urcia, Roby; Boisvert, François-Michel; Vandermoere, Franck; Morrice, Nick A.; Swift, Sam; Rothbauer, Ulrich; Leonhardt, Heinrich; Lamond, Angus

    2008-01-01

    The identification of interaction partners in protein complexes is a major goal in cell biology. Here we present a reliable affinity purification strategy to identify specific interactors that combines quantitative SILAC-based mass spectrometry with characterization of common contaminants binding to affinity matrices (bead proteomes). This strategy can be applied to affinity purification of either tagged fusion protein complexes or endogenous protein complexes, illustrated here using the well-characterized SMN complex as a model. GFP is used as the tag of choice because it shows minimal nonspecific binding to mammalian cell proteins, can be quantitatively depleted from cell extracts, and allows the integration of biochemical protein interaction data with in vivo measurements using fluorescence microscopy. Proteins binding nonspecifically to the most commonly used affinity matrices were determined using quantitative mass spectrometry, revealing important differences that affect experimental design. These data provide a specificity filter to distinguish specific protein binding partners in both quantitative and nonquantitative pull-down and immunoprecipitation experiments. PMID:18936248

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

    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...

  6. Phosphopeptide derivatization signatures to identify serine and threonine phosphorylated peptides by mass spectrometry.

    Molloy, M P; Andrews, P C

    2001-11-15

    The development of rapid, global methods for monitoring states of protein phosphorylation would provide greater insight for understanding many fundamental biological processes. Current best practices use mass spectrometry (MS) to profile digests of purified proteins for evidence of phosphorylation. However, this approach is beset by inherent difficulties in both identifying phosphopeptides from within a complex mixture containing many other unmodified peptides and ionizing phosphopeptides in positive-ion MS. We have modified an approach that uses barium hydroxide to rapidly eliminate the phosphoryl group of serine and threonine modified amino acids, creating dehydroamino acids that are susceptible to nucleophilic derivatization. By derivatizing a protein digest with a mixture of two different alkanethiols, phosphopeptide-specific derivatives were readily distinguished by MS due to their characteristic ion-pair signature. The resulting tagged ion pairs accommodate simple and rapid screening for phosphopeptides in a protein digest, obviating the use of isotopically labeled samples for qualitative phosphopeptide detection. MALDI-MS is used in a first pass manner to detect derivatized phosphopeptides, while the remaining sample is available for tandem MS to reveal the site of derivatization and, thus, phosphorylation. We demonstrated the technique by identifying phosphopeptides from beta-casein and ovalbumin. The approach was further used to examine in vitro phosphorylation of recombinant human HSP22 by protein kinase C, revealing phosphorylation of Thr-63.

  7. Financial crisis and market risk premium: Identifying multiple structural changes

    Juan J. García-Machado

    2011-03-01

    Full Text Available The relationship between macroeconomic variables and stock market returns is, by now, well-documented in the literature. However, in this article we examine the long-run relationship between stock and bond markets returns over the period from 1991:11 to 2009:11, using Bai and Perron’s multiple structural change approach. Findings indicate that while the market risk premium is usually positive, periods with negative values appear only in three periods (1991:1-1993:2, 1998:3-2002:2 and from 2007:1-2009:11 leading to changes in the GDP evolution. Thereby, the study shows the presence of structural breaks in the Spanish market risk premium and its relationship with business cycle. These findings contribute to a better understanding of close linkages between the financial markets and the macroeconomic variables such as GDP. Implications of the study and suggestions for future research are provided.

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

    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

  9. Comparative and bioinformatics analyses of pathogenic bacterial secretomes identified by mass spectrometry in Burkholderia species.

    Nguyen, Thao Thi; Chon, Tae-Soo; Kim, Jaehan; Seo, Young-Su; Heo, Muyoung

    2017-07-01

    Secreted proteins (secretomes) play crucial roles during bacterial pathogenesis in both plant and human hosts. The identification and characterization of secretomes in the two plant pathogens Burkholderia glumae BGR1 and B. gladioli BSR3, which cause diseases in rice such as seedling blight, panicle blight, and grain rot, are important steps to not only understand the disease-causing mechanisms but also find remedies for the diseases. Here, we identified two datasets of secretomes in B. glumae BGR1 and B. gladioli BSR3, which consist of 118 and 111 proteins, respectively, using mass spectrometry approach and literature curation. Next, we characterized the functional properties, potential secretion pathways and sequence information properties of secretomes of two plant pathogens in a comparative analysis by various computational approaches. The ratio of potential non-classically secreted proteins (NCSPs) to classically secreted proteins (CSPs) in B. glumae BGR1 was greater than that in B. gladioli BSR3. For CSPs, the putative hydrophobic regions (PHRs) which are essential for secretion process of CSPs were screened in detail at their N-terminal sequences using hidden Markov model (HMM)-based method. Total 31 pairs of homologous proteins in two bacterial secretomes were indicated based on the global alignment (identity ≥ 70%). Our results may facilitate the understanding of the species-specific features of secretomes in two plant pathogenic Burkholderia species.

  10. Reduction of interferences in graphite furnace atomic absorption spectrometry by multiple linear regression modelling

    Grotti, Marco; Abelmoschi, Maria Luisa; Soggia, Francesco; Tiberiade, Christian; Frache, Roberto

    2000-12-01

    The multivariate effects of Na, K, Mg and Ca as nitrates on the electrothermal atomisation of manganese, cadmium and iron were studied by multiple linear regression modelling. Since the models proved to efficiently predict the effects of the considered matrix elements in a wide range of concentrations, they were applied to correct the interferences occurring in the determination of trace elements in seawater after pre-concentration of the analytes. In order to obtain a statistically significant number of samples, a large volume of the certified seawater reference materials CASS-3 and NASS-3 was treated with Chelex-100 resin; then, the chelating resin was separated from the solution, divided into several sub-samples, each of them was eluted with nitric acid and analysed by electrothermal atomic absorption spectrometry (for trace element determinations) and inductively coupled plasma optical emission spectrometry (for matrix element determinations). To minimise any other systematic error besides that due to matrix effects, accuracy of the pre-concentration step and contamination levels of the procedure were checked by inductively coupled plasma mass spectrometric measurements. Analytical results obtained by applying the multiple linear regression models were compared with those obtained with other calibration methods, such as external calibration using acid-based standards, external calibration using matrix-matched standards and the analyte addition technique. Empirical models proved to efficiently reduce interferences occurring in the analysis of real samples, allowing an improvement of accuracy better than for other calibration methods.

  11. Simultaneous imaging of multiple neurotransmitters and neuroactive substances in the brain by desorption electrospray ionization mass spectrometry.

    Shariatgorji, Mohammadreza; Strittmatter, Nicole; Nilsson, Anna; Källback, Patrik; Alvarsson, Alexandra; Zhang, Xiaoqun; Vallianatou, Theodosia; Svenningsson, Per; Goodwin, Richard J A; Andren, Per E

    2016-08-01

    With neurological processes involving multiple neurotransmitters and neuromodulators, it is important to have the ability to directly map and quantify multiple signaling molecules simultaneously in a single analysis. By utilizing a molecular-specific approach, namely desorption electrospray ionization mass spectrometry imaging (DESI-MSI), we demonstrated that the technique can be used to image multiple neurotransmitters and their metabolites (dopamine, dihydroxyphenylacetic acid, 3-methoxytyramine, serotonin, glutamate, glutamine, aspartate, γ-aminobutyric acid, adenosine) as well as neuroactive drugs (amphetamine, sibutramine, fluvoxamine) and drug metabolites in situ directly in brain tissue sections. The use of both positive and negative ionization modes increased the number of identified molecular targets. Chemical derivatization by charge-tagging the primary amines of molecules significantly increased the sensitivity, enabling the detection of low abundant neurotransmitters and other neuroactive substances previously undetectable by MSI. The sensitivity of the imaging approach of neurochemicals has a great potential in many diverse applications in fields such as neuroscience, pharmacology, drug discovery, neurochemistry, and medicine. Copyright © 2016 Elsevier Inc. All rights reserved.

  12. Simultaneous imaging of multiple neurotransmitters and neuroactive substances in the brain by desorption electrospray ionization mass spectrometry

    Shariatgorji, Mohammadreza; Strittmatter, Nicole; Nilsson, Anna; Kallbäck, Patrik; Alvarsson, Alexandra; Zhang, Xiaoqun; Vallianatou, Theodosia; Svenningsson, Per; Goodwin, Richard J. A.; Andrén, Per E.

    2016-01-01

    With neurological processes involving multiple neurotransmitters and neuromodulators, it is important to have the ability to directly map and quantify multiple signaling molecules simultaneously in a single analysis. By utilizing a molecular-specific approach, namely desorption electrospray ionization mass spectrometry imaging (DESI-MSI), we demonstrated that the technique can be used to image multiple neurotransmitters and their metabolites (dopamine, dihydroxyphenylacetic acid, 3-methoxytyr...

  13. Affinity purification combined with mass spectrometry to identify herpes simplex virus protein-protein interactions.

    Meckes, David G

    2014-01-01

    The identification and characterization of herpes simplex virus protein interaction complexes are fundamental to understanding the molecular mechanisms governing the replication and pathogenesis of the virus. Recent advances in affinity-based methods, mass spectrometry configurations, and bioinformatics tools have greatly increased the quantity and quality of protein-protein interaction datasets. In this chapter, detailed and reliable methods that can easily be implemented are presented for the identification of protein-protein interactions using cryogenic cell lysis, affinity purification, trypsin digestion, and mass spectrometry.

  14. Genome-wide association study identifies multiple susceptibility loci for multiple myeloma

    Mitchell, Jonathan S; Li, Ni; Weinhold, Niels

    2016-01-01

    Multiple myeloma (MM) is a plasma cell malignancy with a significant heritable basis. Genome-wide association studies have transformed our understanding of MM predisposition, but individual studies have had limited power to discover risk loci. Here we perform a meta-analysis of these GWAS, add a ...

  15. Analysis of immune-related loci identifies 48 new susceptibility variants for multiple sclerosis

    Beecham, Ashley H; Patsopoulos, Nikolaos A; Xifara, Dionysia K

    2013-01-01

    Using the ImmunoChip custom genotyping array, we analyzed 14,498 subjects with multiple sclerosis and 24,091 healthy controls for 161,311 autosomal variants and identified 135 potentially associated regions (P...

  16. Melatonin in edible plants identified by radioimmunoassay and by high performance liquid chromatography-mass spectrometry

    Dubbels, R.; Klenke, E.; Schnakenberg, E.; Ehlers, C.; Schloot, W.; Reiter, R.J.; Goebel, A.; Schiware, H.W.

    1995-01-01

    Melatonin, the chief hormone of the pineal gland in vertebrates, is widely distributed in the animal kingdom. Among many functions, melatonin synchronizes circadian and circannual rhythms, stimulates immune function, may increase life span, inhibits growth of cancer cells in vitro and cancer progression and promotion in vivo, and was recently shown to be a potent hydroxyl radical scavenger and antioxidant. Hydroxyl radicals are highly toxic by-products of oxygen metabolism that damage cellular DNA and other macromolecules. Herein we report that melatonin, in varying concentrations, is also found in a variety of plants. Melatonin concentrations, measured in nine different plants by radioimmunoassay, ranged from 0 to 862 pg melatonin/mg protein. The presence of melatonin was verified by gas chromatography/mass spectrometry. Our findings suggest that the consumption of plant materials that contain high levels of melatonin could alter blood melatonin levels of the indole as well as provide protection of macromolecules against oxidative damage. (au) 30 refs

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

    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.

  18. Analysis of immune-related loci identifies 48 new susceptibility variants for multiple sclerosis

    Beecham, Ashley H; Patsopoulos, Nikolaos A; Xifara, Dionysia K; Davis, Mary F; Kemppinen, Anu; Cotsapas, Chris; Shahi, Tejas S; Spencer, Chris; Booth, David; Goris, An; Oturai, Annette; Saarela, Janna; Fontaine, Bertrand; Hemmer, Bernhard; Martin, Claes; Zipp, Frauke; D’alfonso, Sandra; Martinelli-Boneschi, Filippo; Taylor, Bruce; Harbo, Hanne F; Kockum, Ingrid; Hillert, Jan; Olsson, Tomas; Ban, Maria; Oksenberg, Jorge R; Hintzen, Rogier; Barcellos, Lisa F; Agliardi, Cristina; Alfredsson, Lars; Alizadeh, Mehdi; Anderson, Carl; Andrews, Robert; Søndergaard, Helle Bach; Baker, Amie; Band, Gavin; Baranzini, Sergio E; Barizzone, Nadia; Barrett, Jeffrey; Bellenguez, Céline; Bergamaschi, Laura; Bernardinelli, Luisa; Berthele, Achim; Biberacher, Viola; Binder, Thomas M C; Blackburn, Hannah; Bomfim, Izaura L; Brambilla, Paola; Broadley, Simon; Brochet, Bruno; Brundin, Lou; Buck, Dorothea; Butzkueven, Helmut; Caillier, Stacy J; Camu, William; Carpentier, Wassila; Cavalla, Paola; Celius, Elisabeth G; Coman, Irène; Comi, Giancarlo; Corrado, Lucia; Cosemans, Leentje; Cournu-Rebeix, Isabelle; Cree, Bruce A C; Cusi, Daniele; Damotte, Vincent; Defer, Gilles; Delgado, Silvia R; Deloukas, Panos; di Sapio, Alessia; Dilthey, Alexander T; Donnelly, Peter; Dubois, Bénédicte; Duddy, Martin; Edkins, Sarah; Elovaara, Irina; Esposito, Federica; Evangelou, Nikos; Fiddes, Barnaby; Field, Judith; Franke, Andre; Freeman, Colin; Frohlich, Irene Y; Galimberti, Daniela; Gieger, Christian; Gourraud, Pierre-Antoine; Graetz, Christiane; Graham, Andrew; Grummel, Verena; Guaschino, Clara; Hadjixenofontos, Athena; Hakonarson, Hakon; Halfpenny, Christopher; Hall, Gillian; Hall, Per; Hamsten, Anders; Harley, James; Harrower, Timothy; Hawkins, Clive; Hellenthal, Garrett; Hillier, Charles; Hobart, Jeremy; Hoshi, Muni; Hunt, Sarah E; Jagodic, Maja; Jelčić, Ilijas; Jochim, Angela; Kendall, Brian; Kermode, Allan; Kilpatrick, Trevor; Koivisto, Keijo; Konidari, Ioanna; Korn, Thomas; Kronsbein, Helena; Langford, Cordelia; Larsson, Malin; Lathrop, Mark; Lebrun-Frenay, Christine; Lechner-Scott, Jeannette; Lee, Michelle H; Leone, Maurizio A; Leppä, Virpi; Liberatore, Giuseppe; Lie, Benedicte A; Lill, Christina M; Lindén, Magdalena; Link, Jenny; Luessi, Felix; Lycke, Jan; Macciardi, Fabio; Männistö, Satu; Manrique, Clara P; Martin, Roland; Martinelli, Vittorio; Mason, Deborah; Mazibrada, Gordon; McCabe, Cristin; Mero, Inger-Lise; Mescheriakova, Julia; Moutsianas, Loukas; Myhr, Kjell-Morten; Nagels, Guy; Nicholas, Richard; Nilsson, Petra; Piehl, Fredrik; Pirinen, Matti; Price, Siân E; Quach, Hong; Reunanen, Mauri; Robberecht, Wim; Robertson, Neil P; Rodegher, Mariaemma; Rog, David; Salvetti, Marco; Schnetz-Boutaud, Nathalie C; Sellebjerg, Finn; Selter, Rebecca C; Schaefer, Catherine; Shaunak, Sandip; Shen, Ling; Shields, Simon; Siffrin, Volker; Slee, Mark; Sorensen, Per Soelberg; Sorosina, Melissa; Sospedra, Mireia; Spurkland, Anne; Strange, Amy; Sundqvist, Emilie; Thijs, Vincent; Thorpe, John; Ticca, Anna; Tienari, Pentti; van Duijn, Cornelia; Visser, Elizabeth M; Vucic, Steve; Westerlind, Helga; Wiley, James S; Wilkins, Alastair; Wilson, James F; Winkelmann, Juliane; Zajicek, John; Zindler, Eva; Haines, Jonathan L; Pericak-Vance, Margaret A; Ivinson, Adrian J; Stewart, Graeme; Hafler, David; Hauser, Stephen L; Compston, Alastair; McVean, Gil; De Jager, Philip; Sawcer, Stephen; McCauley, Jacob L

    2013-01-01

    Using the ImmunoChip custom genotyping array, we analysed 14,498 multiple sclerosis subjects and 24,091 healthy controls for 161,311 autosomal variants and identified 135 potentially associated regions (p-value multiple sclerosis subjects and 26,703 healthy controls. In these 80,094 individuals of European ancestry we identified 48 new susceptibility variants (p-value multiple sclerosis risk variants in 103 discrete loci outside of the Major Histocompatibility Complex. With high resolution Bayesian fine-mapping, we identified five regions where one variant accounted for more than 50% of the posterior probability of association. This study enhances the catalogue of multiple sclerosis risk variants and illustrates the value of fine-mapping in the resolution of GWAS signals. PMID:24076602

  19. Rapid Classification and Identification of Multiple Microorganisms with Accurate Statistical Significance via High-Resolution Tandem Mass Spectrometry.

    Alves, Gelio; Wang, Guanghui; Ogurtsov, Aleksey Y; Drake, Steven K; Gucek, Marjan; Sacks, David B; Yu, Yi-Kuo

    2018-06-05

    Rapid and accurate identification and classification of microorganisms is of paramount importance to public health and safety. With the advance of mass spectrometry (MS) technology, the speed of identification can be greatly improved. However, the increasing number of microbes sequenced is complicating correct microbial identification even in a simple sample due to the large number of candidates present. To properly untwine candidate microbes in samples containing one or more microbes, one needs to go beyond apparent morphology or simple "fingerprinting"; to correctly prioritize the candidate microbes, one needs to have accurate statistical significance in microbial identification. We meet these challenges by using peptide-centric representations of microbes to better separate them and by augmenting our earlier analysis method that yields accurate statistical significance. Here, we present an updated analysis workflow that uses tandem MS (MS/MS) spectra for microbial identification or classification. We have demonstrated, using 226 MS/MS publicly available data files (each containing from 2500 to nearly 100,000 MS/MS spectra) and 4000 additional MS/MS data files, that the updated workflow can correctly identify multiple microbes at the genus and often the species level for samples containing more than one microbe. We have also shown that the proposed workflow computes accurate statistical significances, i.e., E values for identified peptides and unified E values for identified microbes. Our updated analysis workflow MiCId, a freely available software for Microorganism Classification and Identification, is available for download at https://www.ncbi.nlm.nih.gov/CBBresearch/Yu/downloads.html . Graphical Abstract ᅟ.

  20. Multiple breath washout with a sidestream ultrasonic flow sensor and mass spectrometry: a comparative study.

    Fuchs, Susanne I; Buess, Christian; Lum, Sooky; Kozlowska, Wanda; Stocks, Janet; Gappa, Monika

    2006-12-01

    Over recent years, there has been renewed interest in the multiple breath wash-out (MBW) technique for assessing ventilation inhomogeneity (VI) as a measure of early lung disease in children. While currently considered the gold standard, use of mass spectrometry (MS) to measure MBW is not commercially available, thereby limiting widespread application of this technique. A mainstream ultrasonic flow sensor was marketed for MBW a few years ago, but its use was limited to infants. We have recently undertaken intensive modifications of both hardware and software for the ultrasonic system to extend its use for older children. The aim of the current in vivo study was to compare simultaneous measurements of end-tidal tracer gas concentrations and lung clearance index (LCI) from this modified ultrasonic device with those from a mass spectrometer. Paired measurements of three MBW, using 4% sulfur hexafluoride (SF(6)) as the tracer gas and the two systems in series, were obtained in nine healthy adult volunteers. End-tidal tracer gas concentrations (n = 675 paired values) demonstrated close agreement (95% CI of difference -0.23; -0.17%, r(2) = 1). FRC was slightly higher from the MS (95%CI 0.08;0.17 L), but there was no difference in LCI (95%CI -0.10; 0.3). We conclude, that this ultrasonic prototype system measures end-tidal tracer gas concentration accurately and may therefore be a valid tool for MBW beyond early childhood. This prototype system could be the basis for a commercial device allowing more widespread application of MBW in the near future.

  1. Quantitative Analysis of Bioactive Compounds from Aromatic Plants by Means of Dynamic Headspace Extraction and Multiple Headspace Extraction-Gas Chromatography-Mass Spectrometry

    Omar, Jone; Olivares, Maitane; Alonso, Ibone; Vallejo, Asier; Aizpurua-Olaizola, Oier; Etxebarria, Nestor

    2016-01-01

    Seven monoterpenes in 4 aromatic plants (sage, cardamom, lavender, and rosemary) were quantified in liquid extracts and directly in solid samples by means of dynamic headspace-gas chromatography-mass spectrometry (DHS-GC-MS) and multiple headspace extraction-gas chromatography-mass spectrometry

  2. Cell Surface Proteome of Dental Pulp Stem Cells Identified by Label-Free Mass Spectrometry.

    Christian Niehage

    Full Text Available Multipotent mesenchymal stromal cells (MSCs are promising tools for regenerative medicine. They can be isolated from different sources based on their plastic-adherence property. The identification of reliable cell surface markers thus becomes the Holy Grail for their prospective isolation. Here, we determine the cell surface proteomes of human dental pulp-derived MSCs isolated from single donors after culture expansion in low (2% or high (10% serum-containing media. Cell surface proteins were tagged on intact cells using cell impermeable, cleavable sulfo-NHS-SS-biotin, which allows their enrichment by streptavidin pull-down. For the proteomic analyses, we first compared label-free methods to analyze cell surface proteomes i.e. composition, enrichment and proteomic differences, and we developed a new mathematical model to determine cell surface protein enrichment using a combinatorial gene ontology query. Using this workflow, we identified 101 cluster of differentiation (CD markers and 286 non-CD cell surface proteins. Based on this proteome profiling, we identified 14 cell surface proteins, which varied consistently in abundance when cells were cultured under low or high serum conditions. Collectively, our analytical methods provide a basis for identifying the cell surface proteome of dental pulp stem cells isolated from single donors and its evolution during culture or differentiation. Our data provide a comprehensive cell surface proteome for the precise identification of dental pulp-derived MSC populations and their isolation for potential therapeutic intervention.

  3. BSDB: A New Consistent Designation Scheme for Identifying Objects in Binary and Multiple Stars

    Kovaleva D. A.

    2015-06-01

    Full Text Available The new consistent scheme for designation of objects in binary and multiple systems, BSDB, is described. It was developed in the frame of the Binary star DataBase, BDB (http://www.inasan.ru, due to necessity of a unified and consistent system for designation of objects in the database, and the name of the designation scheme was derived from that of the database. The BSDB scheme covers all types of observational data. Three classes of objects introduced within the BSDB nomenclature provide correct links between objects and data, what is especially important for complex multiple stellar systems. The final stage of establishing the BSDB scheme is compilation of the Identification List of Binaries, ILB, where all known objects in binary and multiple stars are presented with their BSDB identifiers along with identifiers according to major catalogues and lists.

  4. Rational polypharmacology: systematically identifying and engaging multiple drug targets to promote axon growth

    Al-Ali, Hassan; Lee, Do-Hun; Danzi, Matt C.; Nassif, Houssam; Gautam, Prson; Wennerberg, Krister; Zuercher, Bill; Drewry, David H.; Lee, Jae K.; Lemmon, Vance P.; Bixby, John L.

    2016-01-01

    Mammalian Central Nervous System (CNS) neurons regrow their axons poorly following injury, resulting in irreversible functional losses. Identifying therapeutics that encourage CNS axon repair has been difficult, in part because multiple etiologies underlie this regenerative failure. This suggests a particular need for drugs that engage multiple molecular targets. Although multi-target drugs are generally more effective than highly selective alternatives, we lack systematic methods for discovering such drugs. Target-based screening is an efficient technique for identifying potent modulators of individual targets. In contrast, phenotypic screening can identify drugs with multiple targets; however, these targets remain unknown. To address this gap, we combined the two drug discovery approaches using machine learning and information theory. We screened compounds in a phenotypic assay with primary CNS neurons and also in a panel of kinase enzyme assays. We used learning algorithms to relate the compounds’ kinase inhibition profiles to their influence on neurite outgrowth. This allowed us to identify kinases that may serve as targets for promoting neurite outgrowth, as well as others whose targeting should be avoided. We found that compounds that inhibit multiple targets (polypharmacology) promote robust neurite outgrowth in vitro. One compound with exemplary polypharmacology, was found to promote axon growth in a rodent spinal cord injury model. A more general applicability of our approach is suggested by its ability to deconvolve known targets for a breast cancer cell line, as well as targets recently shown to mediate drug resistance. PMID:26056718

  5. Simultaneous Quantification of Apolipoprotein A-I and Apolipoprotein B by Liquid-Chromatography–Multiple-Reaction–Monitoring Mass Spectrometry

    Agger, Sean A.; Marney, Luke C.; Hoofnagle, Andrew N.

    2011-01-01

    BACKGROUND If liquid-chromatography–multiple-reaction–monitoring mass spectrometry (LC-MRM/MS) could be used in the large-scale preclinical verification of putative biomarkers, it would obviate the need for the development of expensive immunoassays. In addition, the translation of novel biomarkers to clinical use would be accelerated if the assays used in preclinical studies were the same as those used in the clinical laboratory. To validate this approach, we developed a multiplexed assay for the quantification of 2 clinically well-known biomarkers in human plasma, apolipoprotein A-I and apolipoprotein B (apoA-I and apoB). METHODS We used PeptideAtlas to identify candidate peptides. Human samples were denatured with urea or trifluoroethanol, reduced and alkylated, and digested with trypsin. We compared reversed-phase chromatographic separation of peptides with normal flow and microflow, and we normalized endogenous peptide peak areas to internal standard peptides. We evaluated different methods of calibration and compared the final method with a nephelometric immunoassay. RESULTS We developed a final method using trifluoroethanol denaturation, 21-h digestion, normal flow chromatography-electrospray ionization, and calibration with a single normal human plasma sample. For samples injected in duplicate, the method had intraassay CVs <6% and interassay CVs <12% for both proteins, and compared well with immunoassay (n = 47; Deming regression, LC-MRM/MS = 1.17 × immunoassay – 36.6; Sx|y = 10.3 for apoA-I and LC-MRM/MS = 1.21 × immunoassay + 7.0; Sx|y = 7.9 for apoB). CONCLUSIONS Multiplexed quantification of proteins in human plasma/serum by LC-MRM/MS is possible and compares well with clinically useful immunoassays. The potential application of single-point calibration to large clinical studies could simplify efforts to reduce day-to-day digestion variability. PMID:20923952

  6. Accurate quantification of 5 German cockroach (GCr) allergens in complex extracts using multiple reaction monitoring mass spectrometry (MRM MS).

    Mindaye, S T; Spiric, J; David, N A; Rabin, R L; Slater, J E

    2017-12-01

    German cockroach (GCr) allergen extracts are complex and heterogeneous products, and methods to better assess their potency and composition are needed for adequate studies of their safety and efficacy. The objective of this study was to develop an assay based on liquid chromatography and multiple reaction monitoring mass spectrometry (LC-MRM MS) for rapid, accurate, and reproducible quantification of 5 allergens (Bla g 1, Bla g 2, Bla g 3, Bla g 4, and Bla g 5) in crude GCr allergen extracts. We first established a comprehensive peptide library of allergens from various commercial extracts as well as recombinant allergens. Peptide mapping was performed using high-resolution MS, and the peptide library was then used to identify prototypic and quantotypic peptides to proceed with MRM method development. Assay development included a systematic optimization of digestion conditions (buffer, digestion time, and trypsin concentration), chromatographic separation, and MS parameters. Robustness and suitability were assessed following ICH (Q2 [R1]) guidelines. The method is precise (RSD  0.99, 0.01-1384 fmol/μL), and sensitive (LLOD and LLOQ MS, we quantified allergens from various commercial GCr extracts and showed considerable variability that may impact clinical efficacy. Our data demonstrate that the LC-MRM MS method is valuable for absolute quantification of allergens in GCr extracts and likely has broader applicability to other complex allergen extracts. Definitive quantification provides a new standard for labelling of allergen extracts, which will inform patient care, enable personalized therapy, and enhance the efficacy of immunotherapy for environmental and food allergies. © 2017 The Authors. Clinical & Experimental Allergy published by John Wiley & Sons Ltd. This article has been contributed to by US Government employees and their work is in the public domain in the USA.

  7. Oligomers, organosulfates, and nitrooxy organosulfates in rainwater identified by ultra-high resolution electrospray ionization FT-ICR mass spectrometry

    K. E. Altieri

    2009-04-01

    Full Text Available Wet deposition is an important removal mechanism for atmospheric organic matter, and a potentially important input for receiving ecosystems, yet less than 50% of rainwater organic matter is considered chemically characterized. Precipitation samples collected in New Jersey, USA, were analyzed by negative ion ultra-high resolution electrospray ionization Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS. Elemental compositions of 552 unique molecular species were determined in the mass range 50–500 Da in the rainwater. Four main groups of organic compounds were identified: compounds containing carbon, hydrogen, and oxygen (CHO only, sulfur (S containing CHOS compounds, nitrogen (N containing CHON compounds, and S- and N- containing CHONS compounds. Organic acids commonly identified in precipitation were detected in the rainwater. Within the four main groups of compounds detected in the rainwater, oligomers, organosulfates, and nitrooxy-organosulfates were assigned based on elemental formula comparisons. The majority of the compounds identified are products of atmospheric reactions and are known contributors to secondary organic aerosol (SOA formed from gas phase, aerosol phase, and in-cloud reactions in the atmosphere. It is suggested that the large uncharacterized component of SOA is the main contributor to the large uncharacterized component of rainwater organic matter.

  8. A search engine to identify pathway genes from expression data on multiple organisms

    Zambon Alexander C

    2007-05-01

    Full Text Available Abstract Background The completion of several genome projects showed that most genes have not yet been characterized, especially in multicellular organisms. Although most genes have unknown functions, a large collection of data is available describing their transcriptional activities under many different experimental conditions. In many cases, the coregulatation of a set of genes across a set of conditions can be used to infer roles for genes of unknown function. Results We developed a search engine, the Multiple-Species Gene Recommender (MSGR, which scans gene expression datasets from multiple organisms to identify genes that participate in a genetic pathway. The MSGR takes a query consisting of a list of genes that function together in a genetic pathway from one of six organisms: Homo sapiens, Drosophila melanogaster, Caenorhabditis elegans, Saccharomyces cerevisiae, Arabidopsis thaliana, and Helicobacter pylori. Using a probabilistic method to merge searches, the MSGR identifies genes that are significantly coregulated with the query genes in one or more of those organisms. The MSGR achieves its highest accuracy for many human pathways when searches are combined across species. We describe specific examples in which new genes were identified to be involved in a neuromuscular signaling pathway and a cell-adhesion pathway. Conclusion The search engine can scan large collections of gene expression data for new genes that are significantly coregulated with a pathway of interest. By integrating searches across organisms, the MSGR can identify pathway members whose coregulation is either ancient or newly evolved.

  9. Identifying multiple influential spreaders in term of the distance-based coloring

    Guo, Lei; Lin, Jian-Hong; Guo, Qiang [Research Center of Complex Systems Science, University of Shanghai for Science and Technology, Shanghai 200093 (China); Liu, Jian-Guo, E-mail: liujg004@ustc.edu.cn [Research Center of Complex Systems Science, University of Shanghai for Science and Technology, Shanghai 200093 (China); Data Science and Cloud Service Research Centre, Shanghai University of Finance and Economics, Shanghai 200433 (China)

    2016-02-22

    Identifying influential nodes is of significance for understanding the dynamics of information diffusion process in complex networks. In this paper, we present an improved distance-based coloring method to identify the multiple influential spreaders. In our method, each node is colored by a kind of color with the rule that the distance between initial nodes is close to the average distance of a network. When all nodes are colored, nodes with the same color are sorted into an independent set. Then we choose the nodes at the top positions of the ranking list according to their centralities. The experimental results for an artificial network and three empirical networks show that, comparing with the performance of traditional coloring method, the improvement ratio of our distance-based coloring method could reach 12.82%, 8.16%, 4.45%, 2.93% for the ER, Erdős, Polblogs and Routers networks respectively. - Highlights: • We present an improved distance-based coloring method to identify the multiple influential spreaders. • Each node is colored by a kind of color where the distance between initial nodes is close to the average distance. • For three empirical networks show that the improvement ratio of our distance-based coloring method could reach 8.16% for the Erdos network.

  10. Identifying multiple influential spreaders in term of the distance-based coloring

    Guo, Lei; Lin, Jian-Hong; Guo, Qiang; Liu, Jian-Guo

    2016-01-01

    Identifying influential nodes is of significance for understanding the dynamics of information diffusion process in complex networks. In this paper, we present an improved distance-based coloring method to identify the multiple influential spreaders. In our method, each node is colored by a kind of color with the rule that the distance between initial nodes is close to the average distance of a network. When all nodes are colored, nodes with the same color are sorted into an independent set. Then we choose the nodes at the top positions of the ranking list according to their centralities. The experimental results for an artificial network and three empirical networks show that, comparing with the performance of traditional coloring method, the improvement ratio of our distance-based coloring method could reach 12.82%, 8.16%, 4.45%, 2.93% for the ER, Erdős, Polblogs and Routers networks respectively. - Highlights: • We present an improved distance-based coloring method to identify the multiple influential spreaders. • Each node is colored by a kind of color where the distance between initial nodes is close to the average distance. • For three empirical networks show that the improvement ratio of our distance-based coloring method could reach 8.16% for the Erdos network.

  11. Multiple strategies of oxygen supply in Drosophila malignancies identify tracheogenesis as a novel cancer hallmark.

    Grifoni, Daniela; Sollazzo, Manuela; Fontana, Elisabetta; Froldi, Francesca; Pession, Annalisa

    2015-03-12

    Angiogenesis is the term used to describe all the alterations in blood vessel growth induced by a tumour mass following hypoxic stress. The occurrence of multiple strategies of vessel recruitment favours drug resistance, greatly complicating the treatment of certain tumours. In Drosophila, oxygen is conveyed to the internal organs by the tracheal system, a closed tubular network whose role in cancer growth is so far unexplored. We found that, as observed in human cancers, Drosophila malignant cells suffer from oxygen shortage, release pro-tracheogenic factors, co-opt nearby vessels and get incorporated into the tracheal walls. We also found that the parallelisms observed in cellular behaviours are supported by genetic and molecular conservation. Finally, we identified a molecular circuitry associated with the differentiation of cancer cells into tracheal cells. In summary, our findings identify tracheogenesis as a novel cancer hallmark in Drosophila, further expanding the power of the fly model in cancer research.

  12. Biomarkers that Discriminate Multiple Myeloma Patients with or without Skeletal Involvement Detected Using SELDI-TOF Mass Spectrometry and Statistical and Machine Learning Tools

    Sudeepa Bhattacharyya

    2006-01-01

    Full Text Available Multiple Myeloma (MM is a severely debilitating neoplastic disease of B cell origin, with the primary source of morbidity and mortality associated with unrestrained bone destruction. Surface enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF MS was used to screen for potential biomarkers indicative of skeletal involvement in patients with MM. Serum samples from 48 MM patients, 24 with more than three bone lesions and 24 with no evidence of bone lesions were fractionated and analyzed in duplicate using copper ion loaded immobilized metal affinity SELDI chip arrays. The spectra obtained were compiled, normalized, and mass peaks with mass-to-charge ratios (m/z between 2000 and 20,000 Da identified. Peak information from all fractions was combined together and analyzed using univariate statistics, as well as a linear, partial least squares discriminant analysis (PLS-DA, and a non-linear, random forest (RF, classification algorithm. The PLS-DA model resulted in prediction accuracy between 96–100%, while the RF model was able to achieve a specificity and sensitivity of 87.5% each. Both models as well as multiple comparison adjusted univariate analysis identified a set of four peaks that were the most discriminating between the two groups of patients and hold promise as potential biomarkers for future diagnostic and/or therapeutic purposes.

  13. SoftSearch: integration of multiple sequence features to identify breakpoints of structural variations.

    Steven N Hart

    Full Text Available BACKGROUND: Structural variation (SV represents a significant, yet poorly understood contribution to an individual's genetic makeup. Advanced next-generation sequencing technologies are widely used to discover such variations, but there is no single detection tool that is considered a community standard. In an attempt to fulfil this need, we developed an algorithm, SoftSearch, for discovering structural variant breakpoints in Illumina paired-end next-generation sequencing data. SoftSearch combines multiple strategies for detecting SV including split-read, discordant read-pair, and unmated pairs. Co-localized split-reads and discordant read pairs are used to refine the breakpoints. RESULTS: We developed and validated SoftSearch using real and synthetic datasets. SoftSearch's key features are 1 not requiring secondary (or exhaustive primary alignment, 2 portability into established sequencing workflows, and 3 is applicable to any DNA-sequencing experiment (e.g. whole genome, exome, custom capture, etc.. SoftSearch identifies breakpoints from a small number of soft-clipped bases from split reads and a few discordant read-pairs which on their own would not be sufficient to make an SV call. CONCLUSIONS: We show that SoftSearch can identify more true SVs by combining multiple sequence features. SoftSearch was able to call clinically relevant SVs in the BRCA2 gene not reported by other tools while offering significantly improved overall performance.

  14. Multiplicity of identified particles in e+e- at the Z0

    Henriques, R.P.

    1999-01-01

    The production rates as a function of ξ p for the identified hadrons π, K and p have been measured by DELPHI in inclusive hadronic Z 0 decays, as well as separately in decays into light and heavy flavors. The RICH detector (ring imaging Cerenkov detector) of DELPHI was used to identify charged hadrons. The vertex detector was used to tag high-purity samples of light and heavy quark flavour events. The results, based on a data sample of 1400000 Z 0 decays collected by DELPHI during 1994, have been compared with the predictions from the JETSET parton shower model and the HERWIG cluster fragmentation model. In general, JETSET describes the measured spectra better. In particular, HERWIG seems to fail in the case of the proton spectra in all flavor samples; overestimates the spectra for all charged particles, pions and kaons in Z 0 →b anti b events and underestimates the corresponding spectra in Z 0 → u anti u, d anti d, s anti s events. The DELPHI results on pions, kaons and protons in the inclusive flavor sample agree well with the results from the ALEPH and SLD collaborations, whereas the proton spectrum in the low ξ p region is in disagreement with the results from the OPAL collaboration. The particle multiplicities in Z 0 →q anti q, Z 0 →b anti b and Z 0 →u anti u, d anti d, s anti s events have been measured; improved results were obtained for kaons and protons in the inclusive and b samples and new results were obtained on the multiplicity of pions, kaons and protons in Z 0 →u anti u, d anti d, s anti s events and on the multiplicity of pions in Z 0 →b anti b events. (orig.)

  15. Database-augmented Mass Spectrometry Analysis of Exosomes Identifies Claudin 3 as a Putative Prostate Cancer Biomarker.

    Worst, Thomas Stefan; von Hardenberg, Jost; Gross, Julia Christina; Erben, Philipp; Schnölzer, Martina; Hausser, Ingrid; Bugert, Peter; Michel, Maurice Stephan; Boutros, Michael

    2017-06-01

    In prostate cancer and other malignancies sensitive and robust biomarkers are lacking or have relevant limitations. Prostate specific antigen (PSA), the only biomarker widely used in prostate cancer, is suffering from low specificity. Exosomes offer new perspectives in the discovery of blood-based biomarkers. Here we present a proof-of principle study for a proteomics-based identification pipeline, implementing existing data sources, to exemplarily identify exosome-based biomarker candidates in prostate cancer.Exosomes from malignant PC3 and benign PNT1A cells and from FBS-containing medium were isolated using sequential ultracentrifugation. Exosome and control samples were analyzed on an LTQ-Orbitrap XL mass spectrometer. Proteomic data is available via ProteomeXchange with identifier PXD003651. We developed a scoring scheme to rank 64 proteins exclusively found in PC3 exosomes, integrating data from four public databases and published mass spectrometry data sets. Among the top candidates, we focused on the tight junction protein claudin 3. Retests under serum-free conditions using immunoblotting and immunogold labeling confirmed the presence of claudin 3 on PC3 exosomes. Claudin 3 levels were determined in the blood plasma of patients with localized ( n = 58; 42 with Gleason score 6-7, 16 with Gleason score ≥8) and metastatic prostate cancer ( n = 11) compared with patients with benign prostatic hyperplasia ( n = 15) and healthy individuals ( n = 15) using ELISA, without prior laborious exosome isolation. ANOVA showed different CLDN3 plasma levels in these groups ( p = 0.004). CLDN3 levels were higher in patients with Gleason ≥8 tumors compared with patients with benign prostatic hyperplasia ( p = 0.012) and Gleason 6-7 tumors ( p = 0.029). In patients with localized tumors CLDN3 levels predicted a Gleason score ≥ 8 (AUC = 0.705; p = 0.016) and did not correlate with serum PSA.By using the described workflow claudin 3 was identified and validated as a

  16. Large-scale neurochemical metabolomics analysis identifies multiple compounds associated with methamphetamine exposure.

    McClay, Joseph L; Adkins, Daniel E; Vunck, Sarah A; Batman, Angela M; Vann, Robert E; Clark, Shaunna L; Beardsley, Patrick M; van den Oord, Edwin J C G

    2013-04-01

    Methamphetamine (MA) is an illegal stimulant drug of abuse with serious negative health consequences. The neurochemical effects of MA have been partially characterized, with a traditional focus on classical neurotransmitter systems. However, these directions have not yet led to novel drug treatments for MA abuse or toxicity. As an alternative approach, we describe here the first application of metabolomics to investigate the neurochemical consequences of MA exposure in the rodent brain. We examined single exposures at 3 mg/kg and repeated exposures at 3 mg/kg over 5 days in eight common inbred mouse strains. Brain tissue samples were assayed using high-throughput gas and liquid chromatography mass spectrometry, yielding quantitative data on >300 unique metabolites. Association testing and false discovery rate control yielded several metabolome-wide significant associations with acute MA exposure, including compounds such as lactate ( p = 4.4 × 10 -5 , q = 0.013), tryptophan ( p = 7.0 × 10 -4 , q = 0.035) and 2-hydroxyglutarate ( p = 1.1 × 10 -4 , q = 0.022). Secondary analyses of MA-induced increase in locomotor activity showed associations with energy metabolites such as succinate ( p = 3.8 × 10 -7 ). Associations specific to repeated (5 day) MA exposure included phosphocholine ( p = 4.0 × 10 -4 , q = 0.087) and ergothioneine ( p = 3.0 × 10 -4 , q = 0.087). Our data appear to confirm and extend existing models of MA action in the brain, whereby an initial increase in energy metabolism, coupled with an increase in behavioral locomotion, gives way to disruption of mitochondria and phospholipid pathways and increased endogenous antioxidant response. Our study demonstrates the power of comprehensive MS-based metabolomics to identify drug-induced changes to brain metabolism and to develop neurochemical models of drug effects.

  17. Development of precise analytical methods for strontium and lanthanide isotopic ratios using multiple collector inductively coupled plasma mass spectrometry

    Ohno, Takeshi; Takaku, Yuichi; Hisamatsu, Shun'ichi

    2007-01-01

    We have developed precise analytical methods for strontium and lanthanide isotopic ratios using multiple collector-ICP-mass spectrometry (MC-ICP-MS) for experimental and environmental studies of their behavior. In order to obtain precise isotopic data using MC-ICP-MS, the mass discrimination effect was corrected by an exponential law correction method. The resulting isotopic data demonstrated that highly precise isotopic analyses (better than 0.1 per mille as 2SD) could be achieved. We also adopted a de-solvating nebulizer system to improve the sensitivity. This system could minimize the water load into the plasma and provided about five times larger intensity of analyte than a conventional nebulizer system did. (author)

  18. High-precision lead isotope ratio measurement by inductively coupled plasma multiple collector mass spectrometry

    Walder, A.J.; Furuta, Naoki.

    1993-01-01

    An inductively coupled plasma (ICP) ion source coupled to a magnetic sector mass analyser equipped with seven Faraday detectors has been used to measure the lead isotope ratios in solutions of Sanshiro Pond sediment collected at the University of Tokyo, airborne particulates collected at Shinjuku in Tokyo and Merck multielement standard product number 97279494. A thallium correction technique was utilized to allow a simultaneous correction for mass bias. This work followed an earlier interlaboratory comparison study of the above-mentioned solutions using ICP quadrupole mass spectrometry, and has demonstrated a considerable improvement in analytical precision. The following isotope ratio measurements were recorded. Pond sediment solution containing 82 ng ml -1 lead: 206 Pb/ 204 Pb=17.762±0.014; 206 Pb/ 207 Pb=1.1424±0.0009; 208 Pb/ 204 Pb=37.678±0.034. Airborne particulate solution containing 45 ng ml -1 lead: 206 Pb/ 204 Pb=17.969±0.006; 206 Pb/ 207 Pb=1.1528±0.0003; 208 Pb/ 204 Pb=37.915±0.021. Merck multielement standard solution containing 100 ng ml -1 lead: 206 Pb/ 204 Pb=19.255±0.015; 206 Pb/ 207 Pb=1.2238±0.0004; 208 Pb/ 204 Pb=38.476±0.021 (All errors are given as ±2 standard deviations). (author)

  19. Identifying the Micro-relations Underpinning Familiarity Detection in Dynamic Displays Containing Multiple Objects

    Jamie S. North

    2017-06-01

    Full Text Available We identified the important micro-relations that are perceived when attempting to recognize patterns in stimuli consisting of multiple dynamic objects. Skilled and less-skilled participants were presented with point light display sequences representing dynamic patterns in an invasion sport and were subsequently required to make familiarity based recognition judgments in three different conditions, each of which contained only a select number of features that were present at initial viewing. No differences in recognition accuracy were observed between skilled and less-skilled participants when just objects located in the periphery were presented. Yet, when presented with the relative motions of two centrally located attacking objects only, skilled participants were significantly more accurate than less-skilled participants and their recognition accuracy improved further when a target object was included against which these relative motions could be judged. Skilled participants can perceive and recognize global patterns on the basis of centrally located relational information.

  20. Serum metabolomic profiling in acute alcoholic hepatitis identifies multiple dysregulated pathways.

    Rachakonda, Vikrant; Gabbert, Charles; Raina, Amit; Bell, Lauren N; Cooper, Sara; Malik, Shahid; Behari, Jaideep

    2014-01-01

    While animal studies have implicated derangements of global energy homeostasis in the pathogenesis of acute alcoholic hepatitis (AAH), the relevance of these findings to the development of human AAH remains unclear. Using global, unbiased serum metabolomics analysis, we sought to characterize alterations in metabolic pathways associated with severe AAH and identify potential biomarkers for disease prognosis. This prospective, case-control study design included 25 patients with severe AAH and 25 ambulatory patients with alcoholic cirrhosis. Serum samples were collected within 24 hours of the index clinical encounter. Global, unbiased metabolomics profiling was performed. Patients were followed for 180 days after enrollment to determine survival. Levels of 234 biochemicals were altered in subjects with severe AAH. Random-forest analysis, principal component analysis, and integrated hierarchical clustering methods demonstrated that metabolomics profiles separated the two cohorts with 100% accuracy. Severe AAH was associated with enhanced triglyceride lipolysis, impaired mitochondrial fatty acid beta oxidation, and upregulated omega oxidation. Low levels of multiple lysolipids and related metabolites suggested decreased plasma membrane remodeling in severe AAH. While most measured bile acids were increased in severe AAH, low deoxycholate and glycodeoxycholate levels indicated intestinal dysbiosis. Several changes in substrate utilization for energy homeostasis were identified in severe AAH, including increased glucose consumption by the pentose phosphate pathway, altered tricarboxylic acid (TCA) cycle activity, and enhanced peptide catabolism. Finally, altered levels of small molecules related to glutathione metabolism and antioxidant vitamin depletion were observed in patients with severe AAH. Univariable logistic regression revealed 15 metabolites associated with 180-day survival in severe AAH. Severe AAH is characterized by a distinct metabolic phenotype spanning

  1. Simultaneous quantification of multiple urinary naphthalene metabolites by liquid chromatography tandem mass spectrometry.

    Daniel C Ayala

    Full Text Available Naphthalene is an environmental toxicant to which humans are exposed. Naphthalene causes dose-dependent cytotoxicity to murine airway epithelial cells but a link between exposure and human pulmonary disease has not been established. Naphthalene toxicity in rodents depends on P450 metabolism. Subsequent biotransformation results in urinary elimination of several conjugated metabolites. Glucuronide and sulfate conjugates of naphthols have been used as markers of naphthalene exposure but, as the current studies demonstrate, these assays provide a limited view of the range of metabolites generated from the parent hydrocarbon. Here, we present a liquid chromatography tandem mass spectrometry method for measurement of the glucuronide and sulfate conjugates of 1-naphthol as well as the mercapturic acids and N-acetyl glutathione conjugates from naphthalene epoxide. Standard curves were linear over 2 log orders. On column detection limits varied from 0.91 to 3.4 ng; limits of quantitation from 1.8 to 6.4 ng. The accuracy of measurement of spiked urine standards was -13.1 to + 5.2% of target and intra-day and inter-day variability averaged 7.2 (± 4.5 and 6.8 (± 5.0 %, respectively. Application of the method to urine collected from mice exposed to naphthalene at 15 ppm (4 hrs showed that glutathione-derived metabolites accounted for 60-70% of the total measured metabolites and sulfate and glucuronide conjugates were eliminated in equal amounts. The method is robust and directly measures several major naphthalene metabolites including those derived from glutathione conjugation of naphthalene epoxide. The assays do not require enzymatic deconjugation, extraction or derivatization thus simplifying sample work up.

  2. Subtle differences in molecular recognition between modified glycopeptide antibiotics and bacterial receptor peptides identified by electrospray ionization mass spectrometry

    Jørgensen, Thomas J. D.; Staroske, T; Roepstorff, P

    1999-01-01

    showing that electrospray ionization mass spectrometry (ESI-MS) can be used in the rapid quantitative analysis of mixtures of vancomycin-group antibiotics and their bacterial cell-wall receptors allowing the identification of even subtle differences in binding constants. Differences in affinities...

  3. Multiplicity fluctuations of identified hadrons in p+p interactions at SPS energies

    Maćkowiak-Pawłowska, Maja

    2014-01-01

    Study of energy and system size fluctuations of identified hadrons is one of the key goals of NA61/SHINE at the CERN SPS. Results may allow to discover the critical point (CP) of strongly interacting matter as well as to uncover properties of the onset of deconfinement (OD). But fluctuations exhibit numerous other sources starting from most basic ones like volume effects and conservation laws. NA49 seems to observe fluctuations related to CP in collisions of medium size nuclei at top SPS energy. However, this result will remain inconclusive until systematic data on energy and system size dependence will be available. Moreover, fluctuations in p+p as well as in Pb+Pb interactions should be better understood. In this contribution results on multiplicity fluctuations of identified hadrons in p+p interactions at the CERN SPS energies will be presented. The NA61 data will be compared with the corresponding results from central Pb+Pb collisions of NA49 in the common acceptance region of both experiments. Moreover, ...

  4. Quantitative analysis of multiple fatty acid ethanolamides using ultra-performance liquid chromatography-tandem mass spectrometry.

    Lin, Lin; Yang, Haifeng; Jones, Peter J H

    2012-12-01

    Fatty acid ethanolamides (FAE) represent a group of lipid signaling molecules associated with many physiological and pharmacological actions; however, low FAE tissue levels pose challenges in terms of analytical characterization. The objective was to develop a competent ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method for analysis of multiple FAE in animal and human tissue samples. Analytes were extracted using lipid-phase and solid-phase extraction procedures. Chromatographic separation was achieved using a gradient elution in 8 min. FAE were quantified by MS/MS in positive electrospray ionization mode. Linearity was shown in lower and higher FAE concentration ranges, with a limit of quantification (LOQ) ≤0.2 ng/ml for FAE including alpha-linolenoylethanolamide (ALEA), arachidonoylethanolamide (AEA), docosahexaenoylethanolamide (DHEA), linoleoylethanolamide (LEA), oleoylethanolamide (OEA) and palmitoylethanolamide (PEA). Accuracy was shown to be between 92.4% and 108.8%, and precision was <10% for all FAE species. In sum, this sensitive and reproducible method can be used to simultaneously determine multiple FAE at low concentrations in order to facilitate further study of the role of FAE on physiological state. Copyright © 2012 Elsevier Ltd. All rights reserved.

  5. FDRAnalysis: a tool for the integrated analysis of tandem mass spectrometry identification results from multiple search engines.

    Wedge, David C; Krishna, Ritesh; Blackhurst, Paul; Siepen, Jennifer A; Jones, Andrew R; Hubbard, Simon J

    2011-04-01

    Confident identification of peptides via tandem mass spectrometry underpins modern high-throughput proteomics. This has motivated considerable recent interest in the postprocessing of search engine results to increase confidence and calculate robust statistical measures, for example through the use of decoy databases to calculate false discovery rates (FDR). FDR-based analyses allow for multiple testing and can assign a single confidence value for both sets and individual peptide spectrum matches (PSMs). We recently developed an algorithm for combining the results from multiple search engines, integrating FDRs for sets of PSMs made by different search engine combinations. Here we describe a web-server and a downloadable application that makes this routinely available to the proteomics community. The web server offers a range of outputs including informative graphics to assess the confidence of the PSMs and any potential biases. The underlying pipeline also provides a basic protein inference step, integrating PSMs into protein ambiguity groups where peptides can be matched to more than one protein. Importantly, we have also implemented full support for the mzIdentML data standard, recently released by the Proteomics Standards Initiative, providing users with the ability to convert native formats to mzIdentML files, which are available to download.

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

    Dominique Rainteau

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

  7. Improved environmental and forensics measurements using multiple ion counters in isotope ratio mass spectrometry

    Goldberg, S.A.; Richter, S.; Schwieters, H.

    2002-01-01

    Full text: A new detector system designed for isotope ratio mass spectrometers provides improved precision on measurements of samples with very low amounts ( -11 grams) of analyte. An array of continuous dynode electron multipliers has been installed on a new ThermoFinnigan MAT Triton thermal ionization mass spectrometer acquired by the New Brunswick Laboratory. These ion counters are modifications of miniaturized, commercially-available continuous dynode electron multipliers. They can be readily installed to replace individual Faraday cups in a multi-detector mass spectrometer or bundled together and located along the detector plane with a set of Faraday cups. On the New Brunswick Laboratory mass spectrometer, nine Faraday cups, one conventional discrete dynode electron multiplier, and seven miniaturized ion counters were installed. Six of the small ion counters were bundled together and positioned on the high mass side of the Low 4 Faraday cup. One additional ion counter was positioned on the low mass side of the Low 4 Faraday cup. This arrangement allows for the simultaneous measurement of all uranium (including 233 U) or plutonium (including 244 Pu) isotopes, and allows for the measurement of larger 238 U intensities on the Faraday cup if needed. Unit mass spacing of U, Pu, or other actinides is readily achieved by the use of a mass dispersion zoom lens. The advantage of multiple ion counting is the simultaneous collection of isotopes. It overcomes many of the problems such as transient signal variation in sample emission and ionization. For a given sample, multiple ion counting generates a greater number of counts for each isotope relative to single detector ion counting and provides improved counting statistics by a factor of two or more. Initial tests indicate that the multiple ion counters exhibit high counting efficiency, a dark noise of less than 10 counts per minute and typically less than 1 count per minute, and show linear response characteristics over

  8. Identifying College Students' Multiple Intelligences to Enhance Motivation and Language Proficiency

    Madkour, Magda; Mohamed, Rafik Ahmed Abdel Moati

    2016-01-01

    While most research studies on the theory of multiple intelligences focused on the application of the multiple intelligences domains as separate components, this quasi-experimental research targeted the effect of multiple intelligences as integrated abilities for teaching and learning English at higher education. The purpose of this study was to…

  9. Characterization of the human plasma phosphoproteome using linear ion trap mass spectrometry and multiple search engines.

    Carrascal, Montserrat; Gay, Marina; Ovelleiro, David; Casas, Vanessa; Gelpí, Emilio; Abian, Joaquin

    2010-02-05

    Major plasma protein families play different roles in blood physiology and hemostasis and in immunodefense. Other proteins in plasma can be involved in signaling as chemical messengers or constitute biological markers of the status of distant tissues. In this respect, the plasma phosphoproteome holds potentially relevant information on the mechanisms modulating these processes through the regulation of protein activity. In this work we describe for the first time a collection of phosphopeptides identified in human plasma using immunoaffinity separation of the seven major serum protein families from other plasma proteins, SCX fractionation, and TiO(2) purification prior to LC-MS/MS analysis. One-hundred and twenty-seven phosphosites in 138 phosphopeptides mapping 70 phosphoproteins were identified with FDR search engines.

  10. Liquid chromatography-electrospray ionization tandem mass spectrometry and dynamic multiple reaction monitoring method for determining multiple pesticide residues in tomato.

    Andrade, G C R M; Monteiro, S H; Francisco, J G; Figueiredo, L A; Botelho, R G; Tornisielo, V L

    2015-05-15

    A quick and sensitive liquid chromatography-electrospray ionization tandem mass spectrometry method, using dynamic multiple reaction monitoring and a 1.8-μm particle size analytical column, was developed to determine 57 pesticides in tomato in a 13-min run. QuEChERS (quick, easy, cheap, effective, rugged, and safe) method for samples preparations and validations was carried out in compliance with EU SANCO guidelines. The method was applied to 58 tomato samples. More than 84% of the compounds investigated showed limits of detection equal to or lower than 5 mg kg(-1). A mild (50%) matrix effect was observed for 72%, 25%, and 3% of the pesticides studied, respectively. Eighty-one percent of the pesticides showed recoveries ranging between 70% and 120%. Twelve pesticides were detected in 35 samples, all below the maximum residue levels permitted in the Brazilian legislation; 15 samples exceeded the maximum residue levels established by the EU legislation for methamidophos; and 10 exceeded limits for acephate and four for bromuconazole. Copyright © 2014 Elsevier Ltd. All rights reserved.

  11. Medical chart validation of an algorithm for identifying multiple sclerosis relapse in healthcare claims.

    Chastek, Benjamin J; Oleen-Burkey, Merrikay; Lopez-Bresnahan, Maria V

    2010-01-01

    Relapse is a common measure of disease activity in relapsing-remitting multiple sclerosis (MS). The objective of this study was to test the content validity of an operational algorithm for detecting relapse in claims data. A claims-based relapse detection algorithm was tested by comparing its detection rate over a 1-year period with relapses identified based on medical chart review. According to the algorithm, MS patients in a US healthcare claims database who had either (1) a primary claim for MS during hospitalization or (2) a corticosteroid claim following a MS-related outpatient visit were designated as having a relapse. Patient charts were examined for explicit indication of relapse or care suggestive of relapse. Positive and negative predictive values were calculated. Medical charts were reviewed for 300 MS patients, half of whom had a relapse according to the algorithm. The claims-based criteria correctly classified 67.3% of patients with relapses (positive predictive value) and 70.0% of patients without relapses (negative predictive value; kappa 0.373: p value of the operational algorithm. Limitations of the algorithm include lack of differentiation between relapsing-remitting MS and other types, and that it does not incorporate measures of function and disability. The claims-based algorithm appeared to successfully detect moderate-to-severe MS relapse. This validated definition can be applied to future claims-based MS studies.

  12. Multiple binding modes of ibuprofen in human serum albumin identified by absolute binding free energy calculations

    Evoli, Stefania

    2016-11-10

    Human serum albumin possesses multiple binding sites and transports a wide range of ligands that include the anti-inflammatory drug ibuprofen. A complete map of the binding sites of ibuprofen in albumin is difficult to obtain in traditional experiments, because of the structural adaptability of this protein in accommodating small ligands. In this work, we provide a set of predictions covering the geometry, affinity of binding and protonation state for the pharmaceutically most active form (S-isomer) of ibuprofen to albumin, by using absolute binding free energy calculations in combination with classical molecular dynamics (MD) simulations and molecular docking. The most favorable binding modes correctly reproduce several experimentally identified binding locations, which include the two Sudlow\\'s drug sites (DS2 and DS1) and the fatty acid binding sites 6 and 2 (FA6 and FA2). Previously unknown details of the binding conformations were revealed for some of them, and formerly undetected binding modes were found in other protein sites. The calculated binding affinities exhibit trends which seem to agree with the available experimental data, and drastically degrade when the ligand is modeled in a protonated (neutral) state, indicating that ibuprofen associates with albumin preferentially in its charged form. These findings provide a detailed description of the binding of ibuprofen, help to explain a wide range of results reported in the literature in the last decades, and demonstrate the possibility of using simulation methods to predict ligand binding to albumin.

  13. A principal component meta-analysis on multiple anthropometric traits identifies novel loci for body shape

    Ried, Janina S.; Jeff M., Janina; Chu, Audrey Y.; Bragg-Gresham, Jennifer L.; van Dongen, Jenny; Huffman, Jennifer E.; Ahluwalia, Tarunveer S.; Cadby, Gemma; Eklund, Niina; Eriksson, Joel; Esko, Tõnu; Feitosa, Mary F.; Goel, Anuj; Gorski, Mathias; Hayward, Caroline; Heard-Costa, Nancy L.; Jackson, Anne U.; Jokinen, Eero; Kanoni, Stavroula; Kristiansson, Kati; Kutalik, Zoltán; Lahti, Jari; Luan, Jian'an; Mägi, Reedik; Mahajan, Anubha; Mangino, Massimo; Medina-Gomez, Carolina; Monda, Keri L.; Nolte, Ilja M.; Pérusse, Louis; Prokopenko, Inga; Qi, Lu; Rose, Lynda M.; Salvi, Erika; Smith, Megan T.; Snieder, Harold; Stančáková, Alena; Ju Sung, Yun; Tachmazidou, Ioanna; Teumer, Alexander; Thorleifsson, Gudmar; van der Harst, Pim; Walker, Ryan W.; Wang, Sophie R.; Wild, Sarah H.; Willems, Sara M.; Wong, Andrew; Zhang, Weihua; Albrecht, Eva; Couto Alves, Alexessander; Bakker, Stephan J. L.; Barlassina, Cristina; Bartz, Traci M.; Beilby, John; Bellis, Claire; Bergman, Richard N.; Bergmann, Sven; Blangero, John; Blüher, Matthias; Boerwinkle, Eric; Bonnycastle, Lori L.; Bornstein, Stefan R.; Bruinenberg, Marcel; Campbell, Harry; Chen, Yii-Der Ida; Chiang, Charleston W. K.; Chines, Peter S.; Collins, Francis S; Cucca, Fracensco; Cupples, L Adrienne; D'Avila, Francesca; de Geus, Eco J .C.; Dedoussis, George; Dimitriou, Maria; Döring, Angela; Eriksson, Johan G.; Farmaki, Aliki-Eleni; Farrall, Martin; Ferreira, Teresa; Fischer, Krista; Forouhi, Nita G.; Friedrich, Nele; Gjesing, Anette Prior; Glorioso, Nicola; Graff, Mariaelisa; Grallert, Harald; Grarup, Niels; Gräßler, Jürgen; Grewal, Jagvir; Hamsten, Anders; Harder, Marie Neergaard; Hartman, Catharina A.; Hassinen, Maija; Hastie, Nicholas; Hattersley, Andrew Tym; Havulinna, Aki S.; Heliövaara, Markku; Hillege, Hans; Hofman, Albert; Holmen, Oddgeir; Homuth, Georg; Hottenga, Jouke-Jan; Hui, Jennie; Husemoen, Lise Lotte; Hysi, Pirro G.; Isaacs, Aaron; Ittermann, Till; Jalilzadeh, Shapour; James, Alan L.; Jørgensen, Torben; Jousilahti, Pekka; Jula, Antti; Marie Justesen, Johanne; Justice, Anne E.; Kähönen, Mika; Karaleftheri, Maria; Tee Khaw, Kay; Keinanen-Kiukaanniemi, Sirkka M.; Kinnunen, Leena; Knekt, Paul B.; Koistinen, Heikki A.; Kolcic, Ivana; Kooner, Ishminder K.; Koskinen, Seppo; Kovacs, Peter; Kyriakou, Theodosios; Laitinen, Tomi; Langenberg, Claudia; Lewin, Alexandra M.; Lichtner, Peter; Lindgren, Cecilia M.; Lindström, Jaana; Linneberg, Allan; Lorbeer, Roberto; Lorentzon, Mattias; Luben, Robert; Lyssenko, Valeriya; Männistö, Satu; Manunta, Paolo; Leach, Irene Mateo; McArdle, Wendy L.; Mcknight, Barbara; Mohlke, Karen L.; Mihailov, Evelin; Milani, Lili; Mills, Rebecca; Montasser, May E.; Morris, Andrew P.; Müller, Gabriele; Musk, Arthur W.; Narisu, Narisu; Ong, Ken K.; Oostra, Ben A.; Osmond, Clive; Palotie, Aarno; Pankow, James S.; Paternoster, Lavinia; Penninx, Brenda W.; Pichler, Irene; Pilia, Maria G.; Polašek, Ozren; Pramstaller, Peter P.; Raitakari, Olli T; Rankinen, Tuomo; Rao, D. C.; Rayner, Nigel W.; Ribel-Madsen, Rasmus; Rice, Treva K.; Richards, Marcus; Ridker, Paul M.; Rivadeneira, Fernando; Ryan, Kathy A.; Sanna, Serena; Sarzynski, Mark A.; Scholtens, Salome; Scott, Robert A.; Sebert, Sylvain; Southam, Lorraine; Sparsø, Thomas Hempel; Steinthorsdottir, Valgerdur; Stirrups, Kathleen; Stolk, Ronald P.; Strauch, Konstantin; Stringham, Heather M.; Swertz, Morris A.; Swift, Amy J.; Tönjes, Anke; Tsafantakis, Emmanouil; van der Most, Peter J.; Van Vliet-Ostaptchouk, Jana V.; Vandenput, Liesbeth; Vartiainen, Erkki; Venturini, Cristina; Verweij, Niek; Viikari, Jorma S.; Vitart, Veronique; Vohl, Marie-Claude; Vonk, Judith M.; Waeber, Gérard; Widén, Elisabeth; Willemsen, Gonneke; Wilsgaard, Tom; Winkler, Thomas W.; Wright, Alan F.; Yerges-Armstrong, Laura M.; Hua Zhao, Jing; Carola Zillikens, M.; Boomsma, Dorret I.; Bouchard, Claude; Chambers, John C.; Chasman, Daniel I.; Cusi, Daniele; Gansevoort, Ron T.; Gieger, Christian; Hansen, Torben; Hicks, Andrew A.; Hu, Frank; Hveem, Kristian; Jarvelin, Marjo-Riitta; Kajantie, Eero; Kooner, Jaspal S.; Kuh, Diana; Kuusisto, Johanna; Laakso, Markku; Lakka, Timo A.; Lehtimäki, Terho; Metspalu, Andres; Njølstad, Inger; Ohlsson, Claes; Oldehinkel, Albertine J.; Palmer, Lyle J.; Pedersen, Oluf; Perola, Markus; Peters, Annette; Psaty, Bruce M.; Puolijoki, Hannu; Rauramaa, Rainer; Rudan, Igor; Salomaa, Veikko; Schwarz, Peter E. H.; Shudiner, Alan R.; Smit, Jan H.; Sørensen, Thorkild I. A.; Spector, Timothy D.; Stefansson, Kari; Stumvoll, Michael; Tremblay, Angelo; Tuomilehto, Jaakko; Uitterlinden, André G.; Uusitupa, Matti; Völker, Uwe; Vollenweider, Peter; Wareham, Nicholas J.; Watkins, Hugh; Wilson, James F.; Zeggini, Eleftheria; Abecasis, Goncalo R.; Boehnke, Michael; Borecki, Ingrid B.; Deloukas, Panos; van Duijn, Cornelia M.; Fox, Caroline; Groop, Leif C.; Heid, Iris M.; Hunter, David J.; Kaplan, Robert C.; McCarthy, Mark I.; North, Kari E.; O'Connell, Jeffrey R.; Schlessinger, David; Thorsteinsdottir, Unnur; Strachan, David P.; Frayling, Timothy; Hirschhorn, Joel N.; Müller-Nurasyid, Martina; Loos, Ruth J. F.

    2016-01-01

    Large consortia have revealed hundreds of genetic loci associated with anthropometric traits, one trait at a time. We examined whether genetic variants affect body shape as a composite phenotype that is represented by a combination of anthropometric traits. We developed an approach that calculates averaged PCs (AvPCs) representing body shape derived from six anthropometric traits (body mass index, height, weight, waist and hip circumference, waist-to-hip ratio). The first four AvPCs explain >99% of the variability, are heritable, and associate with cardiometabolic outcomes. We performed genome-wide association analyses for each body shape composite phenotype across 65 studies and meta-analysed summary statistics. We identify six novel loci: LEMD2 and CD47 for AvPC1, RPS6KA5/C14orf159 and GANAB for AvPC3, and ARL15 and ANP32 for AvPC4. Our findings highlight the value of using multiple traits to define complex phenotypes for discovery, which are not captured by single-trait analyses, and may shed light onto new pathways. PMID:27876822

  14. Multiple gene analyses identify distinct “bois noir” phytoplasma genotypes in the Republic of Macedonia

    Emilija KOSTADINOVSKA

    2015-01-01

    Full Text Available “Bois noir” (BN is a grapevine yellows disease, associated with phytoplasma strains related to ‘Candidatus Phytoplasma solani’, that causes severe losses to viticulture in the Euro-Mediterranean basin. Due to the complex ecological cycle of its etiological agent, BN epidemiology is only partially known, and no effective control strategies have been developed. Numerous studies have focused on molecular characterization of BN phytoplasma strains, to identify molecular markers useful to accurately describe their genetic diversity, geographic distribution and host range. In the present study, a multiple gene analysess were carried out on 16S rRNA, tuf, vmp1, and stamp genes to study the genetic variability among 18 BN phytoplasma strains detected in diverse regions of the Republic of Macedonia. Restriction fragment length polymorphism (RFLP assays showed the presence of one 16S rRNA (16SrXII-A, two tuf (tuf-type a, tuf-type b, five vmp1 (V2-TA, V3, V4, V14, V18, and three stamp (S1, S2, S3 gene patterns among the examined strains. Based on the collective RFLP patterns, seven genotypes (Mac1 to Mac7 were described as evidence for genetic heterogeneity, and highlighting their prevalence and distribution in the investigated regions. Phylogenetic analyses on vmp1 and stamp genes underlined the affiliation of Macedonian BN phytoplasma strains to clusters associated with distinct ecologies.

  15. Multiple-reflection time-of-flight mass spectrometry for in situ applications

    Dickel, T.; Plaß, W.R.; Lang, J.; Ebert, J.; Geissel, H.; Haettner, E.; Jesch, C.; Lippert, W.; Petrick, M.; Scheidenberger, C.; Yavor, M.I.

    2013-01-01

    Highlights: • MR-TOF-MS: huge potential in chemistry, medicine, space science, homeland security. • Compact MR-TOF-MS (length ∼30 cm) with very high mass resolving powers (10 5 ). • Combination of high resolving power (>10 5 ), mobility, API for in situ measurements. • Envisaged applications of mobile MR-TOF-MS. -- Abstract: Multiple-reflection time-of-flight mass spectrometers (MR-TOF-MS) have recently been installed at different low-energy radioactive ion beam facilities. They are used as isobar separators with high ion capacity and as mass spectrometers with high mass resolving power and accuracy for short-lived nuclei. Furthermore, MR-TOF-MS have a huge potential for applications in other fields, such as chemistry, biology, medicine, space science, and homeland security. The development, commissioning and results of an MR-TOF-MS is presented, which serves as proof-of-principle to show that very high mass resolving powers (∼10 5 ) can be achieved in a compact device (length ∼30 cm). Based on this work, an MR-TOF-MS for in situ application has been designed. For the first time, this device combines very high mass resolving power (>10 5 ), mobility, and an atmospheric pressure inlet in one instrument. It will enable in situ measurements without sample preparation at very high mass accuracy. Envisaged applications of this mobile MR-TOF-MS are discussed

  16. Multiple-reflection time-of-flight mass spectrometry for in situ applications

    Dickel, T., E-mail: t.dickel@gsi.de [II. Physikalisches Institut, Justus-Liebig-Universität Gießen, 35392 Gießen (Germany); GSI Helmholtzzentrum für Schwerionenforschung GmbH, Planckstraße 1, 64291 Darmstadt (Germany); Plaß, W.R. [II. Physikalisches Institut, Justus-Liebig-Universität Gießen, 35392 Gießen (Germany); GSI Helmholtzzentrum für Schwerionenforschung GmbH, Planckstraße 1, 64291 Darmstadt (Germany); Lang, J.; Ebert, J. [II. Physikalisches Institut, Justus-Liebig-Universität Gießen, 35392 Gießen (Germany); Geissel, H.; Haettner, E. [II. Physikalisches Institut, Justus-Liebig-Universität Gießen, 35392 Gießen (Germany); GSI Helmholtzzentrum für Schwerionenforschung GmbH, Planckstraße 1, 64291 Darmstadt (Germany); Jesch, C.; Lippert, W.; Petrick, M. [II. Physikalisches Institut, Justus-Liebig-Universität Gießen, 35392 Gießen (Germany); Scheidenberger, C. [II. Physikalisches Institut, Justus-Liebig-Universität Gießen, 35392 Gießen (Germany); GSI Helmholtzzentrum für Schwerionenforschung GmbH, Planckstraße 1, 64291 Darmstadt (Germany); Yavor, M.I. [Institute for Analytical Instrumentation, Russian Academy of Sciences, 190103 St. Petersburg (Russian Federation)

    2013-12-15

    Highlights: • MR-TOF-MS: huge potential in chemistry, medicine, space science, homeland security. • Compact MR-TOF-MS (length ∼30 cm) with very high mass resolving powers (10{sup 5}). • Combination of high resolving power (>10{sup 5}), mobility, API for in situ measurements. • Envisaged applications of mobile MR-TOF-MS. -- Abstract: Multiple-reflection time-of-flight mass spectrometers (MR-TOF-MS) have recently been installed at different low-energy radioactive ion beam facilities. They are used as isobar separators with high ion capacity and as mass spectrometers with high mass resolving power and accuracy for short-lived nuclei. Furthermore, MR-TOF-MS have a huge potential for applications in other fields, such as chemistry, biology, medicine, space science, and homeland security. The development, commissioning and results of an MR-TOF-MS is presented, which serves as proof-of-principle to show that very high mass resolving powers (∼10{sup 5}) can be achieved in a compact device (length ∼30 cm). Based on this work, an MR-TOF-MS for in situ application has been designed. For the first time, this device combines very high mass resolving power (>10{sup 5}), mobility, and an atmospheric pressure inlet in one instrument. It will enable in situ measurements without sample preparation at very high mass accuracy. Envisaged applications of this mobile MR-TOF-MS are discussed.

  17. Multiple-reflection time-of-flight mass spectrometry for in situ applications

    Dickel, T.; Plaß, W. R.; Lang, J.; Ebert, J.; Geissel, H.; Haettner, E.; Jesch, C.; Lippert, W.; Petrick, M.; Scheidenberger, C.; Yavor, M. I.

    2013-12-01

    Multiple-reflection time-of-flight mass spectrometers (MR-TOF-MS) have recently been installed at different low-energy radioactive ion beam facilities. They are used as isobar separators with high ion capacity and as mass spectrometers with high mass resolving power and accuracy for short-lived nuclei. Furthermore, MR-TOF-MS have a huge potential for applications in other fields, such as chemistry, biology, medicine, space science, and homeland security. The development, commissioning and results of an MR-TOF-MS is presented, which serves as proof-of-principle to show that very high mass resolving powers (∼105) can be achieved in a compact device (length ∼30 cm). Based on this work, an MR-TOF-MS for in situ application has been designed. For the first time, this device combines very high mass resolving power (>105), mobility, and an atmospheric pressure inlet in one instrument. It will enable in situ measurements without sample preparation at very high mass accuracy. Envisaged applications of this mobile MR-TOF-MS are discussed.

  18. MrTADFinder: A network modularity based approach to identify topologically associating domains in multiple resolutions.

    Koon-Kiu Yan

    2017-07-01

    Full Text Available Genome-wide proximity ligation based assays such as Hi-C have revealed that eukaryotic genomes are organized into structural units called topologically associating domains (TADs. From a visual examination of the chromosomal contact map, however, it is clear that the organization of the domains is not simple or obvious. Instead, TADs exhibit various length scales and, in many cases, a nested arrangement. Here, by exploiting the resemblance between TADs in a chromosomal contact map and densely connected modules in a network, we formulate TAD identification as a network optimization problem and propose an algorithm, MrTADFinder, to identify TADs from intra-chromosomal contact maps. MrTADFinder is based on the network-science concept of modularity. A key component of it is deriving an appropriate background model for contacts in a random chain, by numerically solving a set of matrix equations. The background model preserves the observed coverage of each genomic bin as well as the distance dependence of the contact frequency for any pair of bins exhibited by the empirical map. Also, by introducing a tunable resolution parameter, MrTADFinder provides a self-consistent approach for identifying TADs at different length scales, hence the acronym "Mr" standing for Multiple Resolutions. We then apply MrTADFinder to various Hi-C datasets. The identified domain boundaries are marked by characteristic signatures in chromatin marks and transcription factors (TF that are consistent with earlier work. Moreover, by calling TADs at different length scales, we observe that boundary signatures change with resolution, with different chromatin features having different characteristic length scales. Furthermore, we report an enrichment of HOT (high-occupancy target regions near TAD boundaries and investigate the role of different TFs in determining boundaries at various resolutions. To further explore the interplay between TADs and epigenetic marks, as tumor mutational

  19. High-precision measurement of variations in calcium isotope ratios in urine by multiple collector inductively coupled plasma mass spectrometry

    Morgan, J.L.L.; Gordon, G.W.; Arrua, R.C.; Skulan, J.L.; Anbar, A.D.; Bullen, T.D.

    2011-01-01

    We describe a new chemical separation method to isolate Ca from other matrix elements in biological samples, developed with the long-term goal of making high-precision measurement of natural stable Ca isotope variations a clinically applicable tool to assess bone mineral balance. A new two-column procedure utilizing HBr achieves the purity required to accurately and precisely measure two Ca isotope ratios (44Ca/42Ca and 44Ca/43Ca) on a Neptune multiple collector inductively coupled plasma mass spectrometer (MC-ICPMS) in urine. Purification requirements for Sr, Ti, and K (Ca/Sr > 10000; Ca/Ti > 10000000; and Ca/K > 10) were determined by addition of these elements to Ca standards of known isotopic composition. Accuracy was determined by (1) comparing Ca isotope results for samples and standards to published data obtained using thermal ionization mass spectrometry (TIMS), (2) adding a Ca standard of known isotopic composition to a urine sample purified of Ca, and (3) analyzing mixtures of urine samples and standards in varying proportions. The accuracy and precision of δ44/42Ca measurements of purified samples containing 25 μg of Ca can be determined with typical errors less than ±0.2‰ (2σ).

  20. PACOM: A Versatile Tool for Integrating, Filtering, Visualizing, and Comparing Multiple Large Mass Spectrometry Proteomics Data Sets.

    Martínez-Bartolomé, Salvador; Medina-Aunon, J Alberto; López-García, Miguel Ángel; González-Tejedo, Carmen; Prieto, Gorka; Navajas, Rosana; Salazar-Donate, Emilio; Fernández-Costa, Carolina; Yates, John R; Albar, Juan Pablo

    2018-04-06

    Mass-spectrometry-based proteomics has evolved into a high-throughput technology in which numerous large-scale data sets are generated from diverse analytical platforms. Furthermore, several scientific journals and funding agencies have emphasized the storage of proteomics data in public repositories to facilitate its evaluation, inspection, and reanalysis. (1) As a consequence, public proteomics data repositories are growing rapidly. However, tools are needed to integrate multiple proteomics data sets to compare different experimental features or to perform quality control analysis. Here, we present a new Java stand-alone tool, Proteomics Assay COMparator (PACOM), that is able to import, combine, and simultaneously compare numerous proteomics experiments to check the integrity of the proteomic data as well as verify data quality. With PACOM, the user can detect source of errors that may have been introduced in any step of a proteomics workflow and that influence the final results. Data sets can be easily compared and integrated, and data quality and reproducibility can be visually assessed through a rich set of graphical representations of proteomics data features as well as a wide variety of data filters. Its flexibility and easy-to-use interface make PACOM a unique tool for daily use in a proteomics laboratory. PACOM is available at https://github.com/smdb21/pacom .

  1. Multiple microflame quartz tube atomizer: Study and minimization of interferences in quartz tube atomizers in hydride generation atomic absorption spectrometry

    Moraes Flores, Erico Marlon de [Departamento de Quimica, Universidade Federal de Santa Maria, 97105-900, Santa Maria, RS (Brazil)], E-mail: flores@quimica.ufsm.br; Medeiros Nunes, Adriane; Luiz Dressler, Valderi [Departamento de Quimica, Universidade Federal de Santa Maria, 97105-900, Santa Maria, RS (Brazil); Dedina, Jiri [Institute of Analytical Chemistry of the ASCR, v.v.i., Videnska 1083, CZ-142 20 Prague (Czech Republic)

    2009-02-15

    A systematic study was performed to evaluate the performance of a multiple microflame (MM) quartz tube atomizer (QTA) for minimizing interferences and to improve the extent of the calibration range using a batch system for hydride generation atomic absorption spectrometry (HG AAS). A comparison of the results with conventional QTA on the determination of antimony, arsenic, bismuth and selenium was performed. The interference of As, Bi, Se, Pb, Sn and Sb was investigated using QTA and MMQTA atomizers. Better performance was found for MMQTA, and no loss of linearity was observed up to 160 ng for Se and Sb and 80 ng for As, corresponding to an enhancement of two times for both analytes when compared to QTA (analyte mass refers to a volume of 200 {mu}l). For Bi, the linear range was the same for QTA and MMQTA (140 ng). With the exception of Bi, the tolerance limits for hydride-forming elements were improved more than 50% in comparison to the conventional QTA system, especially for the interferences of As, Sb and Se. However, for Sn as an interferent, no difference was observed in the determination of Se and Sb using the MMQTA system. The use of MMQTA-HG AAS complied with the relatively high sensitivity of conventional QTA and also provided better performance for interferences and the linear range of calibration.

  2. Nanoelectrospray high capacity ion trap multiple stage mass spectrometry for the structural analysis of human brain gangliosides

    Vukelic, Zeljka; Ratiu, Cornelia; Grozescu, Ioan; Zamfir, Alina Diana

    2006-01-01

    Full text: A novel protocol based on electrospray ionization (ESI) multiple stage high capacity ion trap (HCT) mass spectrometry (MS) was developed for glycosphingolipidomic surveys. The method was optimized for detailed structural elucidation of human brain gangliosides and particularly applied to human hippocampus-associated structures. The multiple stage MS experiments allowed for a complete structural characterization of GM1 ganglioside species, which was achieved by elucidation of the oligosaccharide sequence, identification of the GM1 a structural isomer from the data upon sialic acid localization along the sugar backbone and determination of the d18:1/18:0 of fatty acid/sphingoid base composition of the ceramide moiety. The methodology developed here is of general practical applicability for glycolipids and represents a step forward in the implementation of the advanced and most modern MS methods in glycomics. Gangliosides are glycosphingolipids, which consist of a mono- to polysialylated oligosaccharide chain of variable length attached to a ceramide portion of different composition with respect to the type of sphingoid base and fatty acid residues. Among all body systems, the central nervous system (CNS) possesses the highest content of gangliosides and they are playing a particularly important biological role at this level. Specific changes in the ganglioside expression and type of the expressed structures were observed to occur during brain development, maturation, and aging, and due to diseases or neurodegeneration processes. Gangliosides represent, therefore, an important class of biomarkers, carriers of information upon various CNS processes and events. Though in the human brain, their expression was observed to have a regional and tissue development induced specificity, the differences in ganglioside structure, composition and quantity were not systematically investigated or rigorously determined so far. (authors)

  3. Mass spectrometry and site-directed mutagenesis identify several autophosphorylated residues required for the activity of PrkC, a Ser/Thr kinase from Bacillus subtilis

    Madec, Edwige; Stensballe, Allan; Kjellström, Sven

    2003-01-01

    We have shown recently that PrkC, which is involved in developmental processes in Bacillus subtilis, is a Ser/Thr kinase with features of the receptor kinase family of eukaryotic Hanks kinases. In this study, we expressed and purified from Escherichia coli the cytoplasmic domain of PrkC containing...... the kinase and a short juxtamembrane region. This fragment, which we designate PrkCc, undergoes autophosphorylation in E.coli. PrkCc is further autophosphorylated in vitro, apparently through a trans-kinase, intermolecular reaction. PrkC also displays kinase activity with myelin basic protein. Using high...... mass accuracy electrospray tandem mass spectrometry (LC-MS/MS) and nanoelectrospray tandem mass spectrometry, we identified seven phosphorylated threonine and one serine residue in PrkCc. All the corresponding residues were replaced by systematic site-directed mutagenesis and the purified mutant...

  4. Identifying the Transition between Single and Multiple Mating of Queens in Fungus-Growing Ants

    Villesen, Palle; Murakami, Takahiro; Schultz, Ted R.

    2002-01-01

    Obligate mating of females (queens) with multiple males has evolved only rarely in social Hymenoptera (ants, social bees, social wasps) and for reasons that are fundamentally different from those underlying multiple mating in other animals. The monophyletic tribe of ('attine') fungus-growing ants...

  5. Identifying the transition between single and multiple mating of queens in fungus-growing ants

    Villesen, Palle; Murakami, Takahiro; Schultz, Ted R

    2002-01-01

    Obligate mating of females (queens) with multiple males has evolved only rarely in social Hymenoptera (ants, social bees, social wasps) and for reasons that are fundamentally different from those underlying multiple mating in other animals. The monophyletic tribe of ('attine') fungus-growing ants...

  6. Simultaneous determination of components released from dental composite resins in human saliva by liquid chromatography/multiple-stage ion trap mass spectrometry.

    Hsu, Wei-Yi; Wang, Ven-Shing; Lai, Chien-Chen; Tsai, Fuu-Jen

    2012-02-01

    Dental composite resins are widely used for fixing teeth; however, the monomers used in dental composite resins have been found to be cytotoxic and genotoxic, namely triethylene glycol dimethacrylate (TEGDMA), urethane dimethacrylate (UDMA), and bisphenol A glycol dimethacrylate (Bis-GMA). In this study, we incubated dental composite resins with human saliva for demonstrating the released monomers and biodegradation products. A simple saliva sample dilution method without purification or derivatization was used for quantification. We found that liquid chromatography coupled with multiple-stage ion trap mass spectrometry (LC-MS(n) ) operated in selected reaction monitoring (SRM) mode was able to separate the three monomers within 10 min. The calibration curves were linear (R² >0.996) over a wide range for each monomer in saliva: TEGDMA, 5-500 ppb; UDMA, 5-100 ppb, and Bis-GMA, 5-700 ppb. Furthermore, several biodegradation products were discovered with data-dependent MS/MS scan techniques. Although TEGMA degradation products have previously been reported, we identified two previously unknown UDMA degradation products. The LC-MS/MS method developed in this study was able to successfully quantify monomers and their principal biodegradation products from dental composite resins in human saliva. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  7. Determination of Trace Iron in Red Wine by Isotope Dilution Mass Spectrometry Using Multiple-Collector Inductively Coupled Plasma Mass Spectrometry

    Zhou Tao; Wang Jun; Lu Hai; Zhou Yuanjing; Li Haifeng

    2009-01-01

    This paper introduces determination of trace iron in red wine certified reference material by isotope dilution mass spectrometry (IDMS) method using a multiplecollector inductively coupled plasma mass spectrometry, equipped with a hexapole collision cell. The measurement procedure of iron isotopic abundance ratios was deeply researched. Reduced polyatomic ion interferences to iron isotopes ion by collision reaction using Ar and H 2 gas, high precise isotopic abundance ratios were achieved. Two relative measurement methods (ICP-MS and ICP-OES) were used to analyze trace iron in red wine. The results are compared with IDMS results, which indicate that they are accordant. The uncertainty analyses include each uncertainty factor in whole experiment and the uncertainty of used certified reference material and it shows that the procedure blank is not neglectable to detect limit and precision of the method. The establishment of IDMS method for analysis of trace iron in red wine supports the certification of certified reference materials. (authors)

  8. Multiple inert gas elimination technique by micropore membrane inlet mass spectrometry--a comparison with reference gas chromatography.

    Kretzschmar, Moritz; Schilling, Thomas; Vogt, Andreas; Rothen, Hans Ulrich; Borges, João Batista; Hachenberg, Thomas; Larsson, Anders; Baumgardner, James E; Hedenstierna, Göran

    2013-10-15

    The mismatching of alveolar ventilation and perfusion (VA/Q) is the major determinant of impaired gas exchange. The gold standard for measuring VA/Q distributions is based on measurements of the elimination and retention of infused inert gases. Conventional multiple inert gas elimination technique (MIGET) uses gas chromatography (GC) to measure the inert gas partial pressures, which requires tonometry of blood samples with a gas that can then be injected into the chromatograph. The method is laborious and requires meticulous care. A new technique based on micropore membrane inlet mass spectrometry (MMIMS) facilitates the handling of blood and gas samples and provides nearly real-time analysis. In this study we compared MIGET by GC and MMIMS in 10 piglets: 1) 3 with healthy lungs; 2) 4 with oleic acid injury; and 3) 3 with isolated left lower lobe ventilation. The different protocols ensured a large range of normal and abnormal VA/Q distributions. Eight inert gases (SF6, krypton, ethane, cyclopropane, desflurane, enflurane, diethyl ether, and acetone) were infused; six of these gases were measured with MMIMS, and six were measured with GC. We found close agreement of retention and excretion of the gases and the constructed VA/Q distributions between GC and MMIMS, and predicted PaO2 from both methods compared well with measured PaO2. VA/Q by GC produced more widely dispersed modes than MMIMS, explained in part by differences in the algorithms used to calculate VA/Q distributions. In conclusion, MMIMS enables faster measurement of VA/Q, is less demanding than GC, and produces comparable results.

  9. Isotopic analysis of calcium in blood plasma and bone from mouse samples by multiple collector-ICP-mass spectrometry

    Hirata, Takafumi; Tanoshima, Mina; Suga, Akinobu; Tanaka, Yu-ki; Nagata, Yuichi; Shinohara, Atsuko; Chiba, Momoko

    2008-01-01

    The biological processing of Ca produces significant stable isotope fractionation. The level of isotopic fractionation can provide key information about the variation in dietary consumption or Ca metabolism. To investigate this, we measured the 43 Ca/ 42 Ca and 44 Ca/ 42 Ca ratios for bone and blood plasma samples collected from mice of various ages using multiple collector-ICP-mass spectrometry (MC-ICP-MS). The 44 Ca/ 42 Ca ratio in bones was significantly (0.44 - 0.84 per mille) lower than the corresponding ratios in the diet, suggesting that Ca was isotopically fractionated during Ca metabolism for bone formation. The resulting 44 Ca/ 42 Ca ratios for blood plasma showed almost identical, or slightly higher, values (0.03 - 0.2 per mille) than found in a corresponding diet. This indicates that a significant amount of Ca in the blood plasma was from dietary sources. Unlike that discovered for Fe, there were not significant differences in the measured 44 Ca/ 42 Ca ratios between female and male specimens (for either bone or blood plasma samples). Similarity, the 44 Ca/ 42 Ca ratios suggests that there were no significant differences in Ca dietary consumption or Ca metabolism between female and male specimens. In contrast, the 44 Ca/ 42 Ca ratios of blood plasma from mother mice during the lactation period were significantly higher than those for all other adult specimens. This suggests that Ca supplied to infants through lactation was isotopically lighter, and the preferential supply of isotropically lighter Ca resulted in isotopically heavier Ca in blood plasma of mother mice during the lactation period. The data obtained here clearly demonstrate that the Ca isotopic ratio has a potential to become a new tool for evaluating changes in dietary consumption, or Ca metabolism of animals. (author)

  10. Improved detection of multiple environmental antibiotics through an optimized sample extraction strategy in liquid chromatography-mass spectrometry analysis.

    Yi, Xinzhu; Bayen, Stéphane; Kelly, Barry C; Li, Xu; Zhou, Zhi

    2015-12-01

    A solid-phase extraction/liquid chromatography/electrospray ionization/multi-stage mass spectrometry (SPE-LC-ESI-MS/MS) method was optimized in this study for sensitive and simultaneous detection of multiple antibiotics in urban surface waters and soils. Among the seven classes of tested antibiotics, extraction efficiencies of macrolides, lincosamide, chloramphenicol, and polyether antibiotics were significantly improved under optimized sample extraction pH. Instead of only using acidic extraction in many existing studies, the results indicated that antibiotics with low pK a values (antibiotics with high pK a values (>7) were extracted more efficiently under neutral conditions. The effects of pH were more obvious on polar compounds than those on non-polar compounds. Optimization of extraction pH resulted in significantly improved sample recovery and better detection limits. Compared with reported values in the literature, the average reduction of minimal detection limits obtained in this study was 87.6% in surface waters (0.06-2.28 ng/L) and 67.1% in soils (0.01-18.16 ng/g dry wt). This method was subsequently applied to detect antibiotics in environmental samples in a heavily populated urban city, and macrolides, sulfonamides, and lincomycin were frequently detected. Antibiotics with highest detected concentrations were sulfamethazine (82.5 ng/L) in surface waters and erythromycin (6.6 ng/g dry wt) in soils. The optimized sample extraction strategy can be used to improve the detection of a variety of antibiotics in environmental surface waters and soils.

  11. Identifying the transition between single and multiple mating of queens in fungus-growing ants

    Villesen, Palle; Murakami, Takahiro; Schultz, Ted R

    2002-01-01

    Obligate mating of females (queens) with multiple males has evolved only rarely in social Hymenoptera (ants, social bees, social wasps) and for reasons that are fundamentally different from those underlying multiple mating in other animals. The monophyletic tribe of ('attine') fungus-growing ants...... is known to include evolutionarily derived genera with obligate multiple mating (the Acromyrmex and Atta leafcutter ants) as well as phylogenetically basal genera with exclusively single mating (e.g. Apterostigma, Cyphomyrmex, Myrmicocrypta). All attine genera share the unique characteristic of obligate...... dependence on symbiotic fungus gardens for food, but the sophistication of this symbiosis differs considerably across genera. The lower attine genera generally have small, short-lived colonies and relatively non-specialized fungal symbionts (capable of living independently of their ant hosts), whereas...

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

    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....

  13. Freedom poverty: a new tool to identify the multiple disadvantages affecting those with CVD.

    Callander, Emily J; Schofield, Deborah J; Shrestha, Rupendra N

    2013-06-20

    It is recognised that CVD affects an individual's financial situation, placing them in income poverty. However, recent developments in poverty measurement practice recognises other forms of disadvantage other than low income, such as poor health and insufficient education also affect living standards. Using the Freedom Poverty Measure, the multiple forms of disadvantage experienced by those with no health condition, heart disease, other diseases of the circulatory system, and all other health conditions was assessed using data on the adult Australian population contained in the 2003 Survey of Disability, Ageing and Carers. 24% of those with heart disease and 23% of those with other diseases of the circulatory system were in freedom poverty, suffering from multiple forms of disadvantage. Those with heart disease and those with other diseases of the circulatory system were around three times more likely to be in freedom poverty (OR 3.02, 95% CI: 2.29-3.99, p<.0001; OR 2.78, 95% CI: 1.94-3.98, p<.0001) than those with no health condition. Recognising the multiple forms of disadvantage suffered by those with CVD provides a clearer picture of their living standards than just looking at their income alone and the high proportion of individuals with CVD that are suffering from multiple forms of disadvantage should make them a target for policy makers wishing to improve living standards. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  14. Touching Mercury in Community Media: Identifying Multiple Literacy Learning through Digital Arts Production

    Arndt, Angela E.

    2011-01-01

    Educational paradigm shifts call for 21st century learners to possess the knowledge, skills, abilities, values, and experiences associated with multiple forms of literacy in a participatory learning culture. Contemporary educational systems are slow to adapt. Outside of school, people have to be self-motivated and have access to resources in order…

  15. Detection of a rare BCR-ABL tyrosine kinase fusion protein in H929 multiple myeloma cells using immunoprecipitation (IP)-tandem mass spectrometry (MS/MS).

    Breitkopf, Susanne B; Yuan, Min; Pihan, German A; Asara, John M

    2012-10-02

    Hypothesis directed proteomics offers higher throughput over global analyses. We show that immunoprecipitation (IP)-tandem mass spectrometry (LC-MS/MS) in H929 multiple myeloma (MM) cancer cells led to the discovery of a rare and unexpected BCR-ABL fusion, informing a therapeutic intervention using imatinib (Gleevec). BCR-ABL is the driving mutation in chronic myeloid leukemia (CML) and is uncommon to other cancers. Three different IP-MS experiments central to cell signaling pathways were sufficient to discover a BCR-ABL fusion in H929 cells: phosphotyrosine (pY) peptide IP, p85 regulatory subunit of phosphoinositide-3-kinase (PI3K) IP, and the GRB2 adaptor IP. The pY peptides inform tyrosine kinase activity, p85 IP informs the activating adaptors and receptor tyrosine kinases (RTKs) involved in AKT activation and GRB2 IP identifies RTKs and adaptors leading to ERK activation. Integration of the bait-prey data from the three separate experiments identified the BCR-ABL protein complex, which was confirmed by biochemistry, cytogenetic methods, and DNA sequencing revealed the e14a2 fusion transcript. The tyrosine phosphatase SHP2 and the GAB2 adaptor protein, important for MAPK signaling, were common to all three IP-MS experiments. The comparative treatment of tyrosine kinase inhibitor (TKI) drugs revealed only imatinib, the standard of care in CML, was inhibitory to BCR-ABL leading to down-regulation of pERK and pS6K and inhibiting cell proliferation. These data suggest a model for directed proteomics from patient tumor samples for selecting the appropriate TKI drug(s) based on IP and LC-MS/MS. The data also suggest that MM patients, in addition to CML patients, may benefit from BCR-ABL diagnostic screening.

  16. Mass Spectrometry Imaging Reveals Elevated Glomerular ATP/AMP in Diabetes/obesity and Identifies Sphingomyelin as a Possible Mediator

    Satoshi Miyamoto

    2016-05-01

    Full Text Available AMP-activated protein kinase (AMPK is suppressed in diabetes and may be due to a high ATP/AMP ratio, however the quantitation of nucleotides in vivo has been extremely difficult. Via matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI to localize renal nucleotides we found that the diabetic kidney had a significant increase in glomerular ATP/AMP ratio. Untargeted MALDI-MSI analysis revealed that a specific sphingomyelin species (SM(d18:1/16:0 accumulated in the glomeruli of diabetic and high-fat diet-fed mice compared with wild-type controls. In vitro studies in mesangial cells revealed that exogenous addition of SM(d18:1/16:0 significantly elevated ATP via increased glucose consumption and lactate production with a consequent reduction of AMPK and PGC1α. Furthermore, inhibition of sphingomyelin synthases reversed these effects. Our findings suggest that AMPK is reduced in the diabetic kidney due to an increase in the ATP/AMP ratio and that SM(d18:1/16:0 could be responsible for the enhanced ATP production via activation of the glycolytic pathway.

  17. Tandem affinity purification of histones, coupled to mass spectrometry, identifies associated proteins and new sites of post-translational modification in Saccharomyces cerevisiae.

    Valero, M Luz; Sendra, Ramon; Pamblanco, Mercè

    2016-03-16

    Histones and their post-translational modifications contribute to regulating fundamental biological processes in all eukaryotic cells. We have applied a conventional tandem affinity purification strategy to histones H3 and H4 of the yeast Saccharomyces cerevisiae. Mass spectrometry analysis of the co-purified proteins revealed multiple associated proteins, including core histones, which indicates that tagged histones may be incorporated to the nucleosome particle. Among the many other co-isolated proteins there are histone chaperones, elements of chromatin remodeling, of nucleosome assembly/disassembly, and of histone modification complexes. The histone chaperone Rtt106p, two members of chromatin assembly FACT complex and Psh1p, an ubiquitin ligase, were the most abundant proteins obtained with both H3-TAP and H4-TAP, regardless of the cell extraction medium stringency. Our mass spectrometry analyses have also revealed numerous novel post-translational modifications, including 30 new chemical modifications in histones, mainly by ubiquitination. We have discovered not only new sites of ubiquitination but that, besides lysine, also serine and threonine residues are targets of ubiquitination on yeast histones. Our results show the standard tandem affinity purification procedure is suitable for application to yeast histones, in order to isolate and characterize histone-binding proteins and post-translational modifications, avoiding the bias caused by histone purification from a chromatin-enriched fraction. Copyright © 2016 Elsevier B.V. All rights reserved.

  18. Cross-species multiple environmental stress responses: An integrated approach to identify candidate genes for multiple stress tolerance in sorghum (Sorghum bicolor (L. Moench and related model species.

    Adugna Abdi Woldesemayat

    Full Text Available Crop response to the changing climate and unpredictable effects of global warming with adverse conditions such as drought stress has brought concerns about food security to the fore; crop yield loss is a major cause of concern in this regard. Identification of genes with multiple responses across environmental stresses is the genetic foundation that leads to crop adaptation to environmental perturbations.In this paper, we introduce an integrated approach to assess candidate genes for multiple stress responses across-species. The approach combines ontology based semantic data integration with expression profiling, comparative genomics, phylogenomics, functional gene enrichment and gene enrichment network analysis to identify genes associated with plant stress phenotypes. Five different ontologies, viz., Gene Ontology (GO, Trait Ontology (TO, Plant Ontology (PO, Growth Ontology (GRO and Environment Ontology (EO were used to semantically integrate drought related information.Target genes linked to Quantitative Trait Loci (QTLs controlling yield and stress tolerance in sorghum (Sorghum bicolor (L. Moench and closely related species were identified. Based on the enriched GO terms of the biological processes, 1116 sorghum genes with potential responses to 5 different stresses, such as drought (18%, salt (32%, cold (20%, heat (8% and oxidative stress (25% were identified to be over-expressed. Out of 169 sorghum drought responsive QTLs associated genes that were identified based on expression datasets, 56% were shown to have multiple stress responses. On the other hand, out of 168 additional genes that have been evaluated for orthologous pairs, 90% were conserved across species for drought tolerance. Over 50% of identified maize and rice genes were responsive to drought and salt stresses and were co-located within multifunctional QTLs. Among the total identified multi-stress responsive genes, 272 targets were shown to be co-localized within QTLs

  19. Genome-wide association study identifies multiple risk loci for chronic lymphocytic leukemia

    Berndt, S.I.; Skibola, C.F.; Joseph, V.; Camp, N.J.; Nieters, A.; Wang, Z.; Cozen, W.; Monnereau, A.; Wang, S.S.; Kelly, R.S.; Lan, Q.; Teras, L.R.; Chatterjee, N.; Chung, C.C.; Yeager, M.

    2013-01-01

    Genome-wide association studies (GWAS) have previously identified 13 loci associated with risk of chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL). To identify additional CLL susceptibility loci, we conducted the largest meta-analysis for CLL thus far, including four GWAS with a total of 3,100 individuals with CLL (cases) and 7,667 controls. In the meta-analysis, we identified ten independent associated SNPs in nine new loci at 10q23.31 (ACTA2 or FAS (ACTA2/FAS), P = 1.22 × 10...

  20. Differential Mobility Spectrometry-Mass Spectrometry (DMS-MS) in Radiation Biodosimetry: Rapid and High-Throughput Quantitation of Multiple Radiation Biomarkers in Nonhuman Primate Urine

    Chen, Zhidan; Coy, Stephen L.; Pannkuk, Evan L.; Laiakis, Evagelia C.; Fornace, Albert J.; Vouros, Paul

    2018-05-01

    High-throughput methods to assess radiation exposure are a priority due to concerns that include nuclear power accidents, the spread of nuclear weapon capability, and the risk of terrorist attacks. Metabolomics, the assessment of small molecules in an easily accessible sample, is the most recent method to be applied for the identification of biomarkers of the biological radiation response with a useful dose-response profile. Profiling for biomarker identification is frequently done using an LC-MS platform which has limited throughput due to the time-consuming nature of chromatography. We present here a chromatography-free simplified method for quantitative analysis of seven metabolites in urine with radiation dose-response using urine samples provided from the Pannkuk et al. (2015) study of long-term (7-day) radiation response in nonhuman primates (NHP). The stable isotope dilution (SID) analytical method consists of sample preparation by strong cation exchange-solid phase extraction (SCX-SPE) to remove interferences and concentrate the metabolites of interest, followed by differential mobility spectrometry (DMS) ion filtration to select the ion of interest and reduce chemical background, followed by mass spectrometry (overall SID-SPE-DMS-MS). Since no chromatography is used, calibration curves were prepared rapidly, in under 2 h (including SPE) for six simultaneously analyzed radiation biomarkers. The seventh, creatinine, was measured separately after 2500× dilution. Creatinine plays a dual role, measuring kidney glomerular filtration rate (GFR), and indicating kidney damage at high doses. The current quantitative method using SID-SPE-DMS-MS provides throughput which is 7.5 to 30 times higher than that of LC-MS and provides a path to pre-clinical radiation dose estimation. [Figure not available: see fulltext.

  1. Differential Mobility Spectrometry-Mass Spectrometry (DMS-MS) in Radiation Biodosimetry: Rapid and High-Throughput Quantitation of Multiple Radiation Biomarkers in Nonhuman Primate Urine.

    Chen, Zhidan; Coy, Stephen L; Pannkuk, Evan L; Laiakis, Evagelia C; Fornace, Albert J; Vouros, Paul

    2018-05-07

    High-throughput methods to assess radiation exposure are a priority due to concerns that include nuclear power accidents, the spread of nuclear weapon capability, and the risk of terrorist attacks. Metabolomics, the assessment of small molecules in an easily accessible sample, is the most recent method to be applied for the identification of biomarkers of the biological radiation response with a useful dose-response profile. Profiling for biomarker identification is frequently done using an LC-MS platform which has limited throughput due to the time-consuming nature of chromatography. We present here a chromatography-free simplified method for quantitative analysis of seven metabolites in urine with radiation dose-response using urine samples provided from the Pannkuk et al. (2015) study of long-term (7-day) radiation response in nonhuman primates (NHP). The stable isotope dilution (SID) analytical method consists of sample preparation by strong cation exchange-solid phase extraction (SCX-SPE) to remove interferences and concentrate the metabolites of interest, followed by differential mobility spectrometry (DMS) ion filtration to select the ion of interest and reduce chemical background, followed by mass spectrometry (overall SID-SPE-DMS-MS). Since no chromatography is used, calibration curves were prepared rapidly, in under 2 h (including SPE) for six simultaneously analyzed radiation biomarkers. The seventh, creatinine, was measured separately after 2500× dilution. Creatinine plays a dual role, measuring kidney glomerular filtration rate (GFR), and indicating kidney damage at high doses. The current quantitative method using SID-SPE-DMS-MS provides throughput which is 7.5 to 30 times higher than that of LC-MS and provides a path to pre-clinical radiation dose estimation. Graphical Abstract.

  2. Use of multiple correspondence analysis (MCA) to identify interactive meteorological conditions affecting relative throughfall

    Van Stan, John T.; Gay, Trent E.; Lewis, Elliott S.

    2016-02-01

    Forest canopies alter rainfall reaching the surface by redistributing it as throughfall. Throughfall supplies water and nutrients to a variety of ecohydrological components (soil microbial communities, stream water discharge/chemistry, and stormflow pathways) and is controlled by canopy structural interactions with meteorological conditions across temporal scales. This work introduces and applies multiple correspondence analyses (MCAs) to a range of meteorological thresholds (median intensity, median absolute deviation (MAD) of intensity, median wind-driven droplet inclination angle, and MAD of wind speed) for an example throughfall problem: identification of interacting storm conditions corresponding to temporal concentration in relative throughfall beyond the median observation (⩾73% of rain). MCA results from the example show that equalling or exceeding rain intensity thresholds (median and MAD) corresponded with temporal concentration of relative throughfall across all storms. Under these intensity conditions, two wind mechanisms produced significant correspondences: (1) high, steady wind-driven droplet inclination angles increased surface wetting; and (2) sporadic winds shook entrained droplets from surfaces. A discussion is provided showing that these example MCA findings agree well with previous work relying on more historically common methods (e.g., multiple regression and analytical models). Meteorological threshold correspondences to temporal concentration of relative throughfall at our site may be a function of heavy Tillandsia usneoides coverage. Applications of MCA within other forests may provide useful insights to how temporal throughfall dynamics are affected for drainage pathways dependent on different structures (leaves, twigs, branches, etc.).

  3. An Efficient Stepwise Statistical Test to Identify Multiple Linked Human Genetic Variants Associated with Specific Phenotypic Traits.

    Iksoo Huh

    Full Text Available Recent advances in genotyping methodologies have allowed genome-wide association studies (GWAS to accurately identify genetic variants that associate with common or pathological complex traits. Although most GWAS have focused on associations with single genetic variants, joint identification of multiple genetic variants, and how they interact, is essential for understanding the genetic architecture of complex phenotypic traits. Here, we propose an efficient stepwise method based on the Cochran-Mantel-Haenszel test (for stratified categorical data to identify causal joint multiple genetic variants in GWAS. This method combines the CMH statistic with a stepwise procedure to detect multiple genetic variants associated with specific categorical traits, using a series of associated I × J contingency tables and a null hypothesis of no phenotype association. Through a new stratification scheme based on the sum of minor allele count criteria, we make the method more feasible for GWAS data having sample sizes of several thousands. We also examine the properties of the proposed stepwise method via simulation studies, and show that the stepwise CMH test performs better than other existing methods (e.g., logistic regression and detection of associations by Markov blanket for identifying multiple genetic variants. Finally, we apply the proposed approach to two genomic sequencing datasets to detect linked genetic variants associated with bipolar disorder and obesity, respectively.

  4. GWAS of clinically defined gout and subtypes identifies multiple susceptibility loci that include urate transporter genes

    Nakayama, A.; Nakaoka, H.; Yamamoto, K.; Sakiyama, M.; Shaukat, A.; Toyoda, Y.; Okada, Y.; Kamatani, Y.; Nakamura, T.; Takada, T.; Inoue, K.; Yasujima, T.; Yuasa, H.; Shirahama, Y.; Nakashima, H.; Shimizu, S.; Higashino, T.; Kawamura, Y.; Ogata, H.; Kawaguchi, M.; Ohkawa, Y.; Danjoh, I.; Tokumasu, A.; Ooyama, K.; Ito, T.; Kondo, T.; Wakai, K.; Stiburkova, B.; Pavelka, K.; Stamp, L.K.; Dalbeth, N.; Sakurai, Y.; Suzuki, H; Hosoyamada, M.; Fujimori, S.; Yokoo, T.; Hosoya, T.; Inoue, I.; Takahashi, A.; Kubo, M.; Ooyama, H.; Shimizu, T.; Ichida, K.; Shinomiya, N.; Merriman, T.R.; Matsuo, H.; Andres, M; Joosten, L.A.; Janssen, M.C.H.; Jansen, T.L.; Liote, F.; Radstake, T.R.; Riches, P.L.; So, A.; Tauches, A.K.

    2017-01-01

    OBJECTIVE: A genome-wide association study (GWAS) of gout and its subtypes was performed to identify novel gout loci, including those that are subtype-specific. METHODS: Putative causal association signals from a GWAS of 945 clinically defined gout cases and 1213 controls from Japanese males were

  5. Transcriptome analysis of recurrently deregulated genes across multiple cancers identifies new pan-cancer biomarkers

    Kaczkowski, Bogumil; Tanaka, Yuji; Kawaji, Hideya

    2016-01-01

    Genes that are commonly deregulated in cancer are clinically attractive as candidate pan-diagnostic markers and therapeutic targets. To globally identify such targets, we compared Cap Analysis of Gene Expression (CAGE) profiles from 225 different cancer cell lines and 339 corresponding primary cell...

  6. Integration of multiple networks and pathways identifies cancer driver genes in pan-cancer analysis.

    Cava, Claudia; Bertoli, Gloria; Colaprico, Antonio; Olsen, Catharina; Bontempi, Gianluca; Castiglioni, Isabella

    2018-01-06

    Modern high-throughput genomic technologies represent a comprehensive hallmark of molecular changes in pan-cancer studies. Although different cancer gene signatures have been revealed, the mechanism of tumourigenesis has yet to be completely understood. Pathways and networks are important tools to explain the role of genes in functional genomic studies. However, few methods consider the functional non-equal roles of genes in pathways and the complex gene-gene interactions in a network. We present a novel method in pan-cancer analysis that identifies de-regulated genes with a functional role by integrating pathway and network data. A pan-cancer analysis of 7158 tumour/normal samples from 16 cancer types identified 895 genes with a central role in pathways and de-regulated in cancer. Comparing our approach with 15 current tools that identify cancer driver genes, we found that 35.6% of the 895 genes identified by our method have been found as cancer driver genes with at least 2/15 tools. Finally, we applied a machine learning algorithm on 16 independent GEO cancer datasets to validate the diagnostic role of cancer driver genes for each cancer. We obtained a list of the top-ten cancer driver genes for each cancer considered in this study. Our analysis 1) confirmed that there are several known cancer driver genes in common among different types of cancer, 2) highlighted that cancer driver genes are able to regulate crucial pathways.

  7. Genome-wide association study identifies multiple susceptibility loci for diffuse large B cell lymphoma

    Cerhan, James R.; Berndt, Sonja I.; Vijai, Joseph; Ghesquières, Hervé; McKay, James; Wang, Sophia S.; Wang, Zhaoming; Yeager, Meredith; Conde, Lucia; De Bakker, Paul I W; Nieters, Alexandra; Cox, David; Burdett, Laurie; Monnereau, Alain; Flowers, Christopher R.; De Roos, Anneclaire J.; Brooks-Wilson, Angela R.; Lan, Qing; Severi, Gianluca; Melbye, Mads; Gu, Jian; Jackson, Rebecca D.; Kane, Eleanor; Teras, Lauren R.; Purdue, Mark P.; Vajdic, Claire M.; Spinelli, John J.; Giles, Graham G.; Albanes, Demetrius; Kelly, Rachel S.; Zucca, Mariagrazia; Bertrand, Kimberly A.; Zeleniuch-Jacquotte, Anne; Lawrence, Charles; Hutchinson, Amy; Zhi, Degui; Habermann, Thomas M.; Link, Brian K.; Novak, Anne J.; Dogan, Ahmet; Asmann, Yan W.; Liebow, Mark; Thompson, Carrie A.; Ansell, Stephen M.; Witzig, Thomas E.; Weiner, George J.; Veron, Amelie S.; Zelenika, Diana; Tilly, Hervé; Haioun, Corinne; Molina, Thierry Jo; Hjalgrim, Henrik; Glimelius, Bengt; Adami, Hans Olov; Bracci, Paige M.; Riby, Jacques; Smith, Martyn T.; Holly, Elizabeth A.; Cozen, Wendy; Hartge, Patricia; Morton, Lindsay M.; Severson, Richard K.; Tinker, Lesley F.; North, Kari E.; Becker, Nikolaus; Benavente, Yolanda; Boffetta, Paolo; Brennan, Paul; Foretova, Lenka; Maynadie, Marc; Staines, Anthony; Lightfoot, Tracy; Crouch, Simon; Smith, Alex; Roman, Eve; Diver, W. Ryan; Offit, Kenneth; Zelenetz, Andrew; Klein, Robert J.; Villano, Danylo J.; Zheng, Tongzhang; Zhang, Yawei; Holford, Theodore R.; Kricker, Anne; Turner, Jenny; Southey, Melissa C.; Clavel, Jacqueline; Virtamo, Jarmo; Weinstein, Stephanie; Riboli, Elio; Vineis, Paolo; Kaaks, Rudolph; Trichopoulos, Dimitrios; Vermeulen, Roel C H; Boeing, Heiner; Tjonneland, Anne; Angelucci, Emanuele; Di Lollo, Simonetta; Rais, Marco; Birmann, Brenda M.; Laden, Francine; Giovannucci, Edward; Kraft, Peter; Huang, Jinyan; Ma, Baoshan; Ye, Yuanqing; Chiu, Brian C H; Sampson, Joshua; Liang, Liming; Park, Ju Hyun; Chung, Charles C.; Weisenburger, Dennis D.; Chatterjee, Nilanjan; Fraumeni, Joseph F.; Slager, Susan L.; Wu, Xifeng; De Sanjose, Silvia; Smedby, Karin E.; Salles, Gilles; Skibola, Christine F.; Rothman, Nathaniel; Chanock, Stephen J.

    2014-01-01

    Diffuse large B cell lymphoma (DLBCL) is the most common lymphoma subtype and is clinically aggressive. To identify genetic susceptibility loci for DLBCL, we conducted a meta-analysis of 3 new genome-wide association studies (GWAS) and 1 previous scan, totaling 3,857 cases and 7,666 controls of

  8. Identifying Multiple Levels of Discussion-Based Teaching Strategies for Constructing Scientific Models

    Williams, Grant; Clement, John

    2015-01-01

    This study sought to identify specific types of discussion-based strategies that two successful high school physics teachers using a model-based approach utilized in attempting to foster students' construction of explanatory models for scientific concepts. We found evidence that, in addition to previously documented dialogical strategies that…

  9. Peptides identify multiple hotspots within the ligand binding domain of the TNF receptor 2

    Lennick Michael

    2003-01-01

    Full Text Available Abstract Background Hotspots are defined as the minimal functional domains involved in protein:protein interactions and sufficient to induce a biological response. Results Here we describe the use of complex and high diversity phage display libraries to isolate peptides (called Hotspot Ligands or HSPLs which sub-divide the ligand binding domain of the tumor necrosis factor receptor 2 (TNFR2; p75 into multiple hotspots. We have shown that these libraries could generate HSPLs which not only subdivide hotspots on protein and non-protein targets but act as agonists or antagonists. Using this approach, we generated peptides which were specific for human TNFR2, could be competed by the natural ligands, TNFα and TNFβ and induced an unexpected biological response in a TNFR2-specific manner. Conclusions To our knowledge, this is the first report describing the dissection of the TNFR2 into biologically active hotspots with the concomitant identification of a novel and unexpected biological activity.

  10. GWAS of clinically defined gout and subtypes identifies multiple susceptibility loci that include urate transporter genes

    Nakayama, Akiyoshi; Nakaoka, Hirofumi; Yamamoto, Ken; Sakiyama, Masayuki; Shaukat, Amara; Toyoda, Yu; Okada, Yukinori; Kamatani, Yoichiro; Nakamura, Takahiro; Takada, Tappei; Inoue, Katsuhisa; Yasujima, Tomoya; Yuasa, Hiroaki; Shirahama, Yuko; Nakashima, Hiroshi

    2016-01-01

    Objective A genome-wide association study (GWAS) of gout and its subtypes was performed to identify novel gout loci, including those that are subtype-specific. Methods Putative causal association signals from a GWAS of 945 clinically defined gout cases and 1213 controls from Japanese males were replicated with 1396 cases and 1268 controls using a custom chip of 1961 single nucleotide polymorphisms (SNPs). We also first conducted GWASs of gout subtypes. Replication with Caucasian and New Zeala...

  11. Metastasis-related plasma membrane proteins of human breast cancer cells identified by comparative quantitative mass spectrometry

    Leth-Larsen, Rikke; Lund, Rikke; Hansen, Helle V

    2009-01-01

    The spread of cancer cells from a primary tumor to form metastasis at distant sites is a complex multi-step process. The cancer cell proteins, and plasma membrane proteins in particular, involved in this process are poorly defined and a study of the very early events of the metastatic process using...... clinical samples or in vitro assays is not feasible. We have used a unique model system consisting of two isogenic human breast cancer cell lines that are equally tumorigenic in mice, but while one gives rise to metastasis, the other disseminates single cells that remain dormant at distant organs. Membrane...... purification and comparative quantitative LC-MS/MS proteomic analysis identified 13 membrane proteins that were expressed at higher levels and 3 that were under-expressed in the metastatic compared to the non-metastatic cell line from a total of 1919 identified protein entries. Among the proteins were ecto-5...

  12. CSF Proteomics Identifies Specific and Shared Pathways for Multiple Sclerosis Clinical Subtypes.

    Timucin Avsar

    Full Text Available Multiple sclerosis (MS is an immune-mediated, neuro-inflammatory, demyelinating and neurodegenerative disease of the central nervous system (CNS with a heterogeneous clinical presentation and course. There is a remarkable phenotypic heterogeneity in MS, and the molecular mechanisms underlying it remain unknown. We aimed to investigate further the etiopathogenesis related molecular pathways in subclinical types of MS using proteomic and bioinformatics approaches in cerebrospinal fluids of patients with clinically isolated syndrome, relapsing remitting MS and progressive MS (n=179. Comparison of disease groups with controls revealed a total of 151 proteins that are differentially expressed in clinically different MS subtypes. KEGG analysis using PANOGA tool revealed the disease related pathways including aldosterone-regulated sodium reabsorption (p=8.02x10-5 which is important in the immune cell migration, renin-angiotensin (p=6.88x10-5 system that induces Th17 dependent immunity, notch signaling (p=1.83x10-10 pathway indicating the activated remyelination and vitamin digestion and absorption pathways (p=1.73x10-5. An emerging theme from our studies is that whilst all MS clinical forms share common biological pathways, there are also clinical subtypes specific and pathophysiology related pathways which may have further therapeutic implications.

  13. Synthetic Minority Oversampling Technique and Fractal Dimension for Identifying Multiple Sclerosis

    Zhang, Yu-Dong; Zhang, Yin; Phillips, Preetha; Dong, Zhengchao; Wang, Shuihua

    Multiple sclerosis (MS) is a severe brain disease. Early detection can provide timely treatment. Fractal dimension can provide statistical index of pattern changes with scale at a given brain image. In this study, our team used susceptibility weighted imaging technique to obtain 676 MS slices and 880 healthy slices. We used synthetic minority oversampling technique to process the unbalanced dataset. Then, we used Canny edge detector to extract distinguishing edges. The Minkowski-Bouligand dimension was a fractal dimension estimation method and used to extract features from edges. Single hidden layer neural network was used as the classifier. Finally, we proposed a three-segment representation biogeography-based optimization to train the classifier. Our method achieved a sensitivity of 97.78±1.29%, a specificity of 97.82±1.60% and an accuracy of 97.80±1.40%. The proposed method is superior to seven state-of-the-art methods in terms of sensitivity and accuracy.

  14. A multiple-dimension liquid chromatography coupled with mass spectrometry data strategy for the rapid discovery and identification of unknown compounds from a Chinese herbal formula (Er-xian decoction).

    Wang, Caihong; Zhang, Jinlan; Wu, Caisheng; Wang, Zhe

    2017-10-06

    It is very important to rapidly discover and identify the multiple components of traditional Chinese medicine (TCM) formula. High performance liquid chromatography with high resolution tandem mass spectrometry (HPLC-HRMS/MS) has been widely used to analyze TCM formula and contains multiple-dimension data including retention time (RT), high resolution mass (HRMS), multiple-stage mass spectrometric (MS n ), and isotope intensity distribution (IID) data. So it is very necessary to exploit a useful strategy to utilize multiple-dimension data to rapidly probe structural information and identify chemical compounds. In this study, a new strategy to initiatively use the multiple-dimension LC-MS data has been developed to discover and identify unknown compounds of TCM in many styles. The strategy guarantees the fast discovery of candidate structural information and provides efficient structure clues for identification. The strategy contains four steps in sequence: (1) to discover potential compounds and obtain sub-structure information by the mass spectral tree similarity filter (MTSF) technique, based on HRMS and MS n data; (2) to classify potential compounds into known chemical classes by discriminant analysis (DA) on the basis of RT and HRMS data; (3) to hit the candidate structural information of compounds by intersection sub-structure between MTSF and DA (M,D-INSS); (4) to annotate and confirm candidate structures by IID data. This strategy allowed for the high exclusion efficiency (greater than 41%) of irrelevant ions in er-xian decoction (EXD) while providing accurate structural information of 553 potential compounds and identifying 66 candidates, therefore accelerating and simplifying the discovery and identification of unknown compounds in TCM formula. Copyright © 2017 Elsevier B.V. All rights reserved.

  15. GWAS of clinically defined gout and subtypes identifies multiple susceptibility loci that include urate transporter genes.

    Nakayama, Akiyoshi; Nakaoka, Hirofumi; Yamamoto, Ken; Sakiyama, Masayuki; Shaukat, Amara; Toyoda, Yu; Okada, Yukinori; Kamatani, Yoichiro; Nakamura, Takahiro; Takada, Tappei; Inoue, Katsuhisa; Yasujima, Tomoya; Yuasa, Hiroaki; Shirahama, Yuko; Nakashima, Hiroshi; Shimizu, Seiko; Higashino, Toshihide; Kawamura, Yusuke; Ogata, Hiraku; Kawaguchi, Makoto; Ohkawa, Yasuyuki; Danjoh, Inaho; Tokumasu, Atsumi; Ooyama, Keiko; Ito, Toshimitsu; Kondo, Takaaki; Wakai, Kenji; Stiburkova, Blanka; Pavelka, Karel; Stamp, Lisa K; Dalbeth, Nicola; Sakurai, Yutaka; Suzuki, Hiroshi; Hosoyamada, Makoto; Fujimori, Shin; Yokoo, Takashi; Hosoya, Tatsuo; Inoue, Ituro; Takahashi, Atsushi; Kubo, Michiaki; Ooyama, Hiroshi; Shimizu, Toru; Ichida, Kimiyoshi; Shinomiya, Nariyoshi; Merriman, Tony R; Matsuo, Hirotaka

    2017-05-01

    A genome-wide association study (GWAS) of gout and its subtypes was performed to identify novel gout loci, including those that are subtype-specific. Putative causal association signals from a GWAS of 945 clinically defined gout cases and 1213 controls from Japanese males were replicated with 1396 cases and 1268 controls using a custom chip of 1961 single nucleotide polymorphisms (SNPs). We also first conducted GWASs of gout subtypes. Replication with Caucasian and New Zealand Polynesian samples was done to further validate the loci identified in this study. In addition to the five loci we reported previously, further susceptibility loci were identified at a genome-wide significance level (pgout cases, and NIPAL1 and FAM35A for the renal underexcretion gout subtype. While NIPAL1 encodes a magnesium transporter, functional analysis did not detect urate transport via NIPAL1, suggesting an indirect association with urate handling. Localisation analysis in the human kidney revealed expression of NIPAL1 and FAM35A mainly in the distal tubules, which suggests the involvement of the distal nephron in urate handling in humans. Clinically ascertained male patients with gout and controls of Caucasian and Polynesian ancestries were also genotyped, and FAM35A was associated with gout in all cases. A meta-analysis of the three populations revealed FAM35A to be associated with gout at a genome-wide level of significance (p meta =3.58×10 -8 ). Our findings including novel gout risk loci provide further understanding of the molecular pathogenesis of gout and lead to a novel concept for the therapeutic target of gout/hyperuricaemia. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  16. Prediction potential of candidate biomarker sets identified and validated on gene expression data from multiple datasets

    Karacali Bilge

    2007-10-01

    Full Text Available Abstract Background Independently derived expression profiles of the same biological condition often have few genes in common. In this study, we created populations of expression profiles from publicly available microarray datasets of cancer (breast, lymphoma and renal samples linked to clinical information with an iterative machine learning algorithm. ROC curves were used to assess the prediction error of each profile for classification. We compared the prediction error of profiles correlated with molecular phenotype against profiles correlated with relapse-free status. Prediction error of profiles identified with supervised univariate feature selection algorithms were compared to profiles selected randomly from a all genes on the microarray platform and b a list of known disease-related genes (a priori selection. We also determined the relevance of expression profiles on test arrays from independent datasets, measured on either the same or different microarray platforms. Results Highly discriminative expression profiles were produced on both simulated gene expression data and expression data from breast cancer and lymphoma datasets on the basis of ER and BCL-6 expression, respectively. Use of relapse-free status to identify profiles for prognosis prediction resulted in poorly discriminative decision rules. Supervised feature selection resulted in more accurate classifications than random or a priori selection, however, the difference in prediction error decreased as the number of features increased. These results held when decision rules were applied across-datasets to samples profiled on the same microarray platform. Conclusion Our results show that many gene sets predict molecular phenotypes accurately. Given this, expression profiles identified using different training datasets should be expected to show little agreement. In addition, we demonstrate the difficulty in predicting relapse directly from microarray data using supervised machine

  17. Functional Magnetic Resonance Imaging with Concurrent Urodynamic Testing Identifies Brain Structures Involved in Micturition Cycle in Patients with Multiple Sclerosis.

    Khavari, Rose; Karmonik, Christof; Shy, Michael; Fletcher, Sophie; Boone, Timothy

    2017-02-01

    Neurogenic lower urinary tract dysfunction, which is common in patients with multiple sclerosis, has a significant impact on quality of life. In this study we sought to determine brain activity processes during the micturition cycle in female patients with multiple sclerosis and neurogenic lower urinary tract dysfunction. We report brain activity on functional magnetic resonance imaging and simultaneous urodynamic testing in 23 ambulatory female patients with multiple sclerosis. Individual functional magnetic resonance imaging activation maps at strong desire to void and at initiation of voiding were calculated and averaged at Montreal Neuroimaging Institute. Areas of significant activation were identified in these average maps. Subgroup analysis was performed in patients with elicitable neurogenic detrusor overactivity or detrusor-sphincter dyssynergia. Group analysis of all patients at strong desire to void yielded areas of activation in regions associated with executive function (frontal gyrus), emotional regulation (cingulate gyrus) and motor control (putamen, cerebellum and precuneus). Comparison of the average change in activation between previously reported healthy controls and patients with multiple sclerosis showed predominantly stronger, more focal activation in the former and lower, more diffused activation in the latter. Patients with multiple sclerosis who had demonstrable neurogenic detrusor overactivity and detrusor-sphincter dyssynergia showed a trend toward distinct brain activation at full urge and at initiation of voiding respectively. We successfully studied brain activation during the entire micturition cycle in female patients with neurogenic lower urinary tract dysfunction and multiple sclerosis using a concurrent functional magnetic resonance imaging/urodynamic testing platform. Understanding the central neural processes involved in specific parts of micturition in patients with neurogenic lower urinary tract dysfunction may identify areas

  18. Multiple oncogenic viruses identified in Ocular surface squamous neoplasia in HIV-1 patients

    Bisson Gregory

    2010-03-01

    Full Text Available Abstract Background Ocular surface squamous neoplasia (OSSN is a rare cancer that has increased in incidence with the HIV pandemic in Africa. The underlying cause of this cancer in HIV-infected patients from Botswana is not well defined. Results Tissues were obtained from 28 OSSN and 8 pterygia patients. The tissues analyzed from OSSN patients were 83% positive for EBV, 75% were HPV positive, 70% were KSHV positive, 75% were HSV-1/2 positive, and 61% were CMV positive by PCR. Tissues from pterygium patients were 88% positive for EBV, 75% were HPV positive, 50% were KSHV positive, and 60% were CMV positive. None of the patients were JC or BK positive. In situ hybridization and immunohistochemistry analyses further identified HPV, EBV, and KSHV in a subset of the tissue samples. Conclusion We identified the known oncogenic viruses HPV, KSHV, and EBV in OSSN and pterygia tissues. The presence of these tumor viruses in OSSN suggests that they may contribute to the development of this malignancy in the HIV population. Further studies are necessary to characterize the molecular mechanisms associated with viral antigens and their potential role in the development of OSSN.

  19. A proteomics method using immunoaffinity fluorogenic derivatization-liquid chromatography/tandem mass spectrometry (FD-LC-MS/MS) to identify a set of interacting proteins.

    Nakata, Katsunori; Saitoh, Ryoichi; Ishigai, Masaki; Imai, Kazuhiro

    2018-02-01

    Biological functions in organisms are usually controlled by a set of interacting proteins, and identifying the proteins that interact is useful for understanding the mechanism of the functions. Immunoprecipitation is a method that utilizes the affinity of an antibody to isolate and identify the proteins that have interacted in a biological sample. In this study, the FD-LC-MS/MS method, which involves fluorogenic derivatization followed by separation and quantification by HPLC and finally identification of proteins by HPLC-tandem mass spectrometry, was used to identify proteins in immunoprecipitated samples, using heat shock protein 90 (HSP90) as a model of an interacting protein in HepaRG cells. As a result, HSC70 protein, which was known to form a complex with HSP90, was isolated, together with three different types of HSP90-beta. The results demonstrated that the proposed immunoaffinity-FD-LC-MS/MS method could be useful for simultaneously detecting and identifying the proteins that interact with a certain protein. Copyright © 2017 John Wiley & Sons, Ltd.

  20. Effective spreading from multiple leaders identified by percolation in the susceptible-infected-recovered (SIR) model

    Ji, Shenggong; Lü, Linyuan; Yeung, Chi Ho; Hu, Yanqing

    2017-07-01

    Social networks constitute a new platform for information propagation, but its success is crucially dependent on the choice of spreaders who initiate the spreading of information. In this paper, we remove edges in a network at random and the network segments into isolated clusters. The most important nodes in each cluster then form a set of influential spreaders, such that news propagating from them would lead to extensive coverage and minimal redundancy. The method utilizes the similarities between the segmented networks before percolation and the coverage of information propagation in each social cluster to obtain a set of distributed and coordinated spreaders. Our tests of implementing the susceptible-infected-recovered model on Facebook and Enron email networks show that this method outperforms conventional centrality-based methods in terms of spreadability and coverage redundancy. The suggested way of identifying influential spreaders thus sheds light on a new paradigm of information propagation in social networks.

  1. Meta-analytic framework for sparse K-means to identify disease subtypes in multiple transcriptomic studies.

    Huo, Zhiguang; Ding, Ying; Liu, Silvia; Oesterreich, Steffi; Tseng, George

    Disease phenotyping by omics data has become a popular approach that potentially can lead to better personalized treatment. Identifying disease subtypes via unsupervised machine learning is the first step towards this goal. In this paper, we extend a sparse K -means method towards a meta-analytic framework to identify novel disease subtypes when expression profiles of multiple cohorts are available. The lasso regularization and meta-analysis identify a unique set of gene features for subtype characterization. An additional pattern matching reward function guarantees consistent subtype signatures across studies. The method was evaluated by simulations and leukemia and breast cancer data sets. The identified disease subtypes from meta-analysis were characterized with improved accuracy and stability compared to single study analysis. The breast cancer model was applied to an independent METABRIC dataset and generated improved survival difference between subtypes. These results provide a basis for diagnosis and development of targeted treatments for disease subgroups.

  2. A Common Ancestral Mutation in CRYBB3 Identified in Multiple Consanguineous Families with Congenital Cataracts.

    Xiaodong Jiao

    Full Text Available This study was performed to investigate the genetic determinants of autosomal recessive congenital cataracts in large consanguineous families.Affected individuals underwent a detailed ophthalmological examination and slit-lamp photographs of the cataractous lenses were obtained. An aliquot of blood was collected from all participating family members and genomic DNA was extracted from white blood cells. Initially, a genome-wide scan was performed with genomic DNAs of family PKCC025 followed by exclusion analysis of our familial cohort of congenital cataracts. Protein-coding exons of CRYBB1, CRYBB2, CRYBB3, and CRYBA4 were sequenced bidirectionally. A haplotype was constructed with SNPs flanking the causal mutation for affected individuals in all four families, while the probability that the four familial cases have a common founder was estimated using EM and CHM-based algorithms. The expression of Crybb3 in the developing murine lens was investigated using TaqMan assays.The clinical and ophthalmological examinations suggested that all affected individuals had nuclear cataracts. Genome-wide linkage analysis localized the causal phenotype in family PKCC025 to chromosome 22q with statistically significant two-point logarithm of odds (LOD scores. Subsequently, we localized three additional families, PKCC063, PKCC131, and PKCC168 to chromosome 22q. Bidirectional Sanger sequencing identified a missense variation: c.493G>C (p.Gly165Arg in CRYBB3 that segregated with the disease phenotype in all four familial cases. This variation was not found in ethnically matched control chromosomes, the NHLBI exome variant server, or the 1000 Genomes or dbSNP databases. Interestingly, all four families harbor a unique disease haplotype that strongly suggests a common founder of the causal mutation (p<1.64E-10. We observed expression of Crybb3 in the mouse lens as early as embryonic day 15 (E15, and expression remained relatively steady throughout development.Here, we

  3. Multiple distinct subtypes of GABAergic neurons in mouse visual cortex identified by triple immunostaining

    Yuri Gonchar

    2008-03-01

    Full Text Available The majority of cortical interneurons use GABA (gamma amino butyric acid as inhibitory neurotransmitter. GABAergic neurons are morphologically, connectionally, electrically and chemically heterogeneous. In rat cerebral cortex three distinct groups of GABAergic interneurons have been identifi ed by the expression of parvalbumin (PV, calretinin (CR and somatostatin (SOM. Recent studies in mouse cerebral cortex have revealed a different organization in which the CR and SOM populations are partially overlapping. Because CR and SOM neurons derive from different progenitors located in different embryonic structures, the coexpression of CR + SOM suggests that the chemical differentiation of interneurons is regulated postmitotically. Here, we have taken an important fi rst step towards understanding this process by triple immunostaining mouse visual cortex with a panel of antibodies, which has been used extensively for classifying developing interneurons. We have found at least 13 distinct groups of GABAergic neurons which include PV, CR, SOM, CCK (cholecystokinin, CR + SOM, CR + NPY (neuropeptide Y, CR + VIP (vasointestinal polypeptide, SOM + NPY, SOM + VIP, VIP + ChAT (choline acetyltransferase, CCK + NPY, CR + SOM + NPY and CR + SOM + VIP expressing cells. Triple immunostaining with PV, CR and SOM antibodies during postnatal development further showed that PV is never colocalized with CR and SOM. Importantly, expression of SOM and CR + SOM developed after the percentage of CR cells that do not express SOM has reached the mature level, suggesting that the chemical differentiation of SOM and CR + SOM neurons is a postnatal event, which may be controlled by transcriptional regulation.

  4. Efficient genome-wide association in biobanks using topic modeling identifies multiple novel disease loci.

    McCoy, Thomas H; Castro, Victor M; Snapper, Leslie A; Hart, Kamber L; Perlis, Roy H

    2017-08-31

    Biobanks and national registries represent a powerful tool for genomic discovery, but rely on diagnostic codes that may be unreliable and fail to capture the relationship between related diagnoses. We developed an efficient means of conducting genome-wide association studies using combinations of diagnostic codes from electronic health records (EHR) for 10845 participants in a biobanking program at two large academic medical centers. Specifically, we applied latent Dirichilet allocation to fit 50 disease topics based on diagnostic codes, then conducted genome-wide common-variant association for each topic. In sensitivity analysis, these results were contrasted with those obtained from traditional single-diagnosis phenome-wide association analysis, as well as those in which only a subset of diagnostic codes are included per topic. In meta-analysis across three biobank cohorts, we identified 23 disease-associated loci with p<1e-15, including previously associated autoimmune disease loci. In all cases, observed significant associations were of greater magnitude than for single phenome-wide diagnostic codes, and incorporation of less strongly-loading diagnostic codes enhanced association. This strategy provides a more efficient means of phenome-wide association in biobanks with coded clinical data.

  5. Quantification of methionine and selenomethionine in biological samples using multiple reaction monitoring high performance liquid chromatography tandem mass spectrometry (MRM-HPLC-MS/MS).

    Vu, Dai Long; Ranglová, Karolína; Hájek, Jan; Hrouzek, Pavel

    2018-05-01

    Quantification of selenated amino-acids currently relies on methods employing inductively coupled plasma mass spectrometry (ICP-MS). Although very accurate, these methods do not allow the simultaneous determination of standard amino-acids, hampering the comparison of the content of selenated versus non-selenated species such as methionine (Met) and selenomethionine (SeMet). This paper reports two approaches for the simultaneous quantification of Met and SeMet. In the first approach, standard enzymatic hydrolysis employing Protease XIV was applied for the preparation of samples. The second approach utilized methanesulfonic acid (MA) for the hydrolysis of samples, either in a reflux system or in a microwave oven, followed by derivatization with diethyl ethoxymethylenemalonate. The prepared samples were then analyzed by multiple reaction monitoring high performance liquid chromatography tandem mass spectrometry (MRM-HPLC-MS/MS). Both approaches provided platforms for the accurate determination of selenium/sulfur substitution rate in Met. Moreover the second approach also provided accurate simultaneous quantification of Met and SeMet with a low limit of detection, low limit of quantification and wide linearity range, comparable to the commonly used gas chromatography mass spectrometry (GC-MS) method or ICP-MS. The novel method was validated using certified reference material in conjunction with the GC-MS reference method. Copyright © 2018. Published by Elsevier B.V.

  6. Genome-wide meta-analyses identify multiple loci associated with smoking behavior.

    2010-05-01

    Consistent but indirect evidence has implicated genetic factors in smoking behavior. We report meta-analyses of several smoking phenotypes within cohorts of the Tobacco and Genetics Consortium (n = 74,053). We also partnered with the European Network of Genetic and Genomic Epidemiology (ENGAGE) and Oxford-GlaxoSmithKline (Ox-GSK) consortia to follow up the 15 most significant regions (n > 140,000). We identified three loci associated with number of cigarettes smoked per day. The strongest association was a synonymous 15q25 SNP in the nicotinic receptor gene CHRNA3 (rs1051730[A], beta = 1.03, standard error (s.e.) = 0.053, P = 2.8 x 10(-73)). Two 10q25 SNPs (rs1329650[G], beta = 0.367, s.e. = 0.059, P = 5.7 x 10(-10); and rs1028936[A], beta = 0.446, s.e. = 0.074, P = 1.3 x 10(-9)) and one 9q13 SNP in EGLN2 (rs3733829[G], beta = 0.333, s.e. = 0.058, P = 1.0 x 10(-8)) also exceeded genome-wide significance for cigarettes per day. For smoking initiation, eight SNPs exceeded genome-wide significance, with the strongest association at a nonsynonymous SNP in BDNF on chromosome 11 (rs6265[C], odds ratio (OR) = 1.06, 95% confidence interval (Cl) 1.04-1.08, P = 1.8 x 10(-8)). One SNP located near DBH on chromosome 9 (rs3025343[G], OR = 1.12, 95% Cl 1.08-1.18, P = 3.6 x 10(-8)) was significantly associated with smoking cessation.

  7. Newborn blood spot screening for sickle cell disease by using tandem mass spectrometry: implementation of a protocol to identify only the disease states of sickle cell disease.

    Moat, Stuart J; Rees, Derek; King, Lawrence; Ifederu, Adeboye; Harvey, Katie; Hall, Kate; Lloyd, Geoff; Morrell, Christine; Hillier, Sharon

    2014-02-01

    The currently recommended technologies of HPLC and isoelectric focusing for newborn blood spot screening for sickle cell disease (SCD) identify both the disease and carrier states, resulting in large numbers of infants being followed up unnecessarily. Analysis of blood spot tryptic peptides performed by using tandem mass spectrometry (MS/MS) is an alternative technology to detect hemoglobin (Hb) variant disorders. We analyzed 2154 residual newborn blood spots and 675 newborn blood spots from infants with Hb variants by using MS/MS after trypsin digestion. Screening cutoffs were developed by using the ratio between the variant peptide-to-wild-type peptide abundance for HbS, C, D(Punjab), O(Arab), Lepore, and E peptides. A postanalytical data analysis protocol was developed using these cutoffs to detect only the disease states of SCD and not to identify carrier states. A parallel study of 13 249 newborn blood spots from a high-prevalence SCD area were analyzed by both MS/MS and HPLC. Screening cutoffs developed distinguished the infants with the disease states of SCD, infants who were carriers of SCD, and infants with normal Hb. In the parallel study no false-negative results were identified, and all clinically relevant cases were correctly identified using the MS/MS protocol. Unblinding the data revealed a total of 328 carrier infants that were successfully excluded by the protocol. The screening protocol developed correctly identified infants with the disease states of SCD. Furthermore, large numbers of sickle cell carrier infants were successfully not identified, thereby avoiding unnecessary follow-up testing and referral for genetic counseling.

  8. Semi-automated literature mining to identify putative biomarkers of disease from multiple biofluids

    2014-01-01

    Background Computational methods for mining of biomedical literature can be useful in augmenting manual searches of the literature using keywords for disease-specific biomarker discovery from biofluids. In this work, we develop and apply a semi-automated literature mining method to mine abstracts obtained from PubMed to discover putative biomarkers of breast and lung cancers in specific biofluids. Methodology A positive set of abstracts was defined by the terms ‘breast cancer’ and ‘lung cancer’ in conjunction with 14 separate ‘biofluids’ (bile, blood, breastmilk, cerebrospinal fluid, mucus, plasma, saliva, semen, serum, synovial fluid, stool, sweat, tears, and urine), while a negative set of abstracts was defined by the terms ‘(biofluid) NOT breast cancer’ or ‘(biofluid) NOT lung cancer.’ More than 5.3 million total abstracts were obtained from PubMed and examined for biomarker-disease-biofluid associations (34,296 positive and 2,653,396 negative for breast cancer; 28,355 positive and 2,595,034 negative for lung cancer). Biological entities such as genes and proteins were tagged using ABNER, and processed using Python scripts to produce a list of putative biomarkers. Z-scores were calculated, ranked, and used to determine significance of putative biomarkers found. Manual verification of relevant abstracts was performed to assess our method’s performance. Results Biofluid-specific markers were identified from the literature, assigned relevance scores based on frequency of occurrence, and validated using known biomarker lists and/or databases for lung and breast cancer [NCBI’s On-line Mendelian Inheritance in Man (OMIM), Cancer Gene annotation server for cancer genomics (CAGE), NCBI’s Genes & Disease, NCI’s Early Detection Research Network (EDRN), and others]. The specificity of each marker for a given biofluid was calculated, and the performance of our semi-automated literature mining method assessed for breast and lung cancer

  9. Identifying and exploiting trait-relevant tissues with multiple functional annotations in genome-wide association studies

    Zhang, Shujun

    2018-01-01

    Genome-wide association studies (GWASs) have identified many disease associated loci, the majority of which have unknown biological functions. Understanding the mechanism underlying trait associations requires identifying trait-relevant tissues and investigating associations in a trait-specific fashion. Here, we extend the widely used linear mixed model to incorporate multiple SNP functional annotations from omics studies with GWAS summary statistics to facilitate the identification of trait-relevant tissues, with which to further construct powerful association tests. Specifically, we rely on a generalized estimating equation based algorithm for parameter inference, a mixture modeling framework for trait-tissue relevance classification, and a weighted sequence kernel association test constructed based on the identified trait-relevant tissues for powerful association analysis. We refer to our analytic procedure as the Scalable Multiple Annotation integration for trait-Relevant Tissue identification and usage (SMART). With extensive simulations, we show how our method can make use of multiple complementary annotations to improve the accuracy for identifying trait-relevant tissues. In addition, our procedure allows us to make use of the inferred trait-relevant tissues, for the first time, to construct more powerful SNP set tests. We apply our method for an in-depth analysis of 43 traits from 28 GWASs using tissue-specific annotations in 105 tissues derived from ENCODE and Roadmap. Our results reveal new trait-tissue relevance, pinpoint important annotations that are informative of trait-tissue relationship, and illustrate how we can use the inferred trait-relevant tissues to construct more powerful association tests in the Wellcome trust case control consortium study. PMID:29377896

  10. Identifying and exploiting trait-relevant tissues with multiple functional annotations in genome-wide association studies.

    Xingjie Hao

    2018-01-01

    Full Text Available Genome-wide association studies (GWASs have identified many disease associated loci, the majority of which have unknown biological functions. Understanding the mechanism underlying trait associations requires identifying trait-relevant tissues and investigating associations in a trait-specific fashion. Here, we extend the widely used linear mixed model to incorporate multiple SNP functional annotations from omics studies with GWAS summary statistics to facilitate the identification of trait-relevant tissues, with which to further construct powerful association tests. Specifically, we rely on a generalized estimating equation based algorithm for parameter inference, a mixture modeling framework for trait-tissue relevance classification, and a weighted sequence kernel association test constructed based on the identified trait-relevant tissues for powerful association analysis. We refer to our analytic procedure as the Scalable Multiple Annotation integration for trait-Relevant Tissue identification and usage (SMART. With extensive simulations, we show how our method can make use of multiple complementary annotations to improve the accuracy for identifying trait-relevant tissues. In addition, our procedure allows us to make use of the inferred trait-relevant tissues, for the first time, to construct more powerful SNP set tests. We apply our method for an in-depth analysis of 43 traits from 28 GWASs using tissue-specific annotations in 105 tissues derived from ENCODE and Roadmap. Our results reveal new trait-tissue relevance, pinpoint important annotations that are informative of trait-tissue relationship, and illustrate how we can use the inferred trait-relevant tissues to construct more powerful association tests in the Wellcome trust case control consortium study.

  11. Variant-aware saturating mutagenesis using multiple Cas9 nucleases identifies regulatory elements at trait-associated loci.

    Canver, Matthew C; Lessard, Samuel; Pinello, Luca; Wu, Yuxuan; Ilboudo, Yann; Stern, Emily N; Needleman, Austen J; Galactéros, Frédéric; Brugnara, Carlo; Kutlar, Abdullah; McKenzie, Colin; Reid, Marvin; Chen, Diane D; Das, Partha Pratim; A Cole, Mitchel; Zeng, Jing; Kurita, Ryo; Nakamura, Yukio; Yuan, Guo-Cheng; Lettre, Guillaume; Bauer, Daniel E; Orkin, Stuart H

    2017-04-01

    Cas9-mediated, high-throughput, saturating in situ mutagenesis permits fine-mapping of function across genomic segments. Disease- and trait-associated variants identified in genome-wide association studies largely cluster at regulatory loci. Here we demonstrate the use of multiple designer nucleases and variant-aware library design to interrogate trait-associated regulatory DNA at high resolution. We developed a computational tool for the creation of saturating-mutagenesis libraries with single or multiple nucleases with incorporation of variants. We applied this methodology to the HBS1L-MYB intergenic region, which is associated with red-blood-cell traits, including fetal hemoglobin levels. This approach identified putative regulatory elements that control MYB expression. Analysis of genomic copy number highlighted potential false-positive regions, thus emphasizing the importance of off-target analysis in the design of saturating-mutagenesis experiments. Together, these data establish a widely applicable high-throughput and high-resolution methodology to identify minimal functional sequences within large disease- and trait-associated regions.

  12. Metabolites of 5F-AKB-48, a synthetic cannabinoid receptor agonist, identified in human urine and liver microsomal preparations using liquid chromatography high-resolution mass spectrometry.

    Holm, Niels Bjerre; Pedersen, Anders Just; Dalsgaard, Petur Weihe; Linnet, Kristian

    2015-03-01

    New types of synthetic cannabinoid designer drugs are constantly introduced to the illicit drug market to circumvent legislation. Recently, N-​(1-Adamant​yl)-​1-​(5-​fluoropentyl)-​1H-​indazole-​3-​carboxamide (5F-AKB-48), also known as 5F-APINACA, was identified as an adulterant in herbal products. This compound deviates from earlier JHW-type synthetic cannabinoids by having an indazole ring connected to an adamantyl group via a carboxamide linkage. Synthetic cannabinoids are completely metabolized, and identification of the metabolites is thus crucial when using urine as the sample matrix. Using an authentic urine sample and high-resolution accurate-mass Fourier transform Orbitrap mass spectrometry, we identified 16 phase-I metabolites of 5F-AKB-48. The modifications included mono-, di-, and trihydroxylation on the adamantyl ring alone or in combination with hydroxylation on the N-fluoropentylindazole moiety, dealkylation of the N-fluoropentyl side chain, and oxidative loss of fluorine as well as combinations thereof. The results were compared to human liver microsomal (HLM) incubations, which predominantly showed time-dependent formation of mono-, di-, and trihydroxylated metabolites having the hydroxyl groups on the adamantyl ring. The results presented here may be used to select metabolites specific of 5F-AKB-48 for use in clinical and forensic screening. Copyright © 2014 John Wiley & Sons, Ltd.

  13. Urinary Metabolomic Profiling to Identify Potential Biomarkers for the Diagnosis of Behcet’s Disease by Gas Chromatography/Time-of-Flight−Mass Spectrometry

    Joong Kyong Ahn

    2017-11-01

    Full Text Available Diagnosing Behcet’s disease (BD is challenging because of the lack of a diagnostic biomarker. The purposes of this study were to investigate distinctive metabolic changes in urine samples of BD patients and to identify urinary metabolic biomarkers for diagnosis of BD using gas chromatography/time-of-flight–mass spectrometry (GC/TOF−MS. Metabolomic profiling of urine samples from 44 BD patients and 41 healthy controls (HC were assessed using GC/TOF−MS, in conjunction with multivariate statistical analysis. A total of 110 urinary metabolites were identified. The urine metabolite profiles obtained from GC/TOF−MS analysis could distinguish BD patients from the HC group in the discovery set. The parameter values of the orthogonal partial least squared-discrimination analysis (OPLS-DA model were R2X of 0.231, R2Y of 0.804, and Q2 of 0.598. A biomarker panel composed of guanine, pyrrole-2-carboxylate, 3-hydroxypyridine, mannose, l-citrulline, galactonate, isothreonate, sedoheptuloses, hypoxanthine, and gluconic acid lactone were selected and adequately validated as putative biomarkers of BD (sensitivity 96.7%, specificity 93.3%, area under the curve 0.974. OPLS-DA showed clear discrimination of BD and HC groups by a biomarker panel of ten metabolites in the independent set (accuracy 88%. We demonstrated characteristic urinary metabolic profiles and potential urinary metabolite biomarkers that have clinical value in the diagnosis of BD using GC/TOF−MS.

  14. Novel fluorinated surfactants tentatively identified in firefighters using liquid chromatography quadrupole time-of-flight tandem mass spectrometry and a case-control approach.

    Rotander, Anna; Kärrman, Anna; Toms, Leisa-Maree L; Kay, Margaret; Mueller, Jochen F; Gómez Ramos, María José

    2015-02-17

    Fluorinated surfactant-based aqueous film-forming foams (AFFFs) are made up of per- and polyfluorinated alkyl substances (PFAS) and are used to extinguish fires involving highly flammable liquids. The use of perfluorooctanesulfonic acid (PFOS) and other perfluoroalkyl acids (PFAAs) in some AFFF formulations has been linked to substantial environmental contamination. Recent studies have identified a large number of novel and infrequently reported fluorinated surfactants in different AFFF formulations. In this study, a strategy based on a case-control approach using quadrupole time-of-flight tandem mass spectrometry (QTOF-MS/MS) and advanced statistical methods has been used to extract and identify known and unknown PFAS in human serum associated with AFFF-exposed firefighters. Two target sulfonic acids [PFOS and perfluorohexanesulfonic acid (PFHxS)], three non-target acids [perfluoropentanesulfonic acid (PFPeS), perfluoroheptanesulfonic acid (PFHpS), and perfluorononanesulfonic acid (PFNS)], and four unknown sulfonic acids (Cl-PFOS, ketone-PFOS, ether-PFHxS, and Cl-PFHxS) were exclusively or significantly more frequently detected at higher levels in firefighters compared to controls. The application of this strategy has allowed for identification of previously unreported fluorinated chemicals in a timely and cost-efficient way.

  15. A Meta-analysis of Multiple Myeloma Risk Regions in African and European Ancestry Populations Identifies Putatively Functional Loci.

    Rand, Kristin A; Song, Chi; Dean, Eric; Serie, Daniel J; Curtin, Karen; Sheng, Xin; Hu, Donglei; Huff, Carol Ann; Bernal-Mizrachi, Leon; Tomasson, Michael H; Ailawadhi, Sikander; Singhal, Seema; Pawlish, Karen; Peters, Edward S; Bock, Cathryn H; Stram, Alex; Van Den Berg, David J; Edlund, Christopher K; Conti, David V; Zimmerman, Todd; Hwang, Amie E; Huntsman, Scott; Graff, John; Nooka, Ajay; Kong, Yinfei; Pregja, Silvana L; Berndt, Sonja I; Blot, William J; Carpten, John; Casey, Graham; Chu, Lisa; Diver, W Ryan; Stevens, Victoria L; Lieber, Michael R; Goodman, Phyllis J; Hennis, Anselm J M; Hsing, Ann W; Mehta, Jayesh; Kittles, Rick A; Kolb, Suzanne; Klein, Eric A; Leske, Cristina; Murphy, Adam B; Nemesure, Barbara; Neslund-Dudas, Christine; Strom, Sara S; Vij, Ravi; Rybicki, Benjamin A; Stanford, Janet L; Signorello, Lisa B; Witte, John S; Ambrosone, Christine B; Bhatti, Parveen; John, Esther M; Bernstein, Leslie; Zheng, Wei; Olshan, Andrew F; Hu, Jennifer J; Ziegler, Regina G; Nyante, Sarah J; Bandera, Elisa V; Birmann, Brenda M; Ingles, Sue A; Press, Michael F; Atanackovic, Djordje; Glenn, Martha J; Cannon-Albright, Lisa A; Jones, Brandt; Tricot, Guido; Martin, Thomas G; Kumar, Shaji K; Wolf, Jeffrey L; Deming Halverson, Sandra L; Rothman, Nathaniel; Brooks-Wilson, Angela R; Rajkumar, S Vincent; Kolonel, Laurence N; Chanock, Stephen J; Slager, Susan L; Severson, Richard K; Janakiraman, Nalini; Terebelo, Howard R; Brown, Elizabeth E; De Roos, Anneclaire J; Mohrbacher, Ann F; Colditz, Graham A; Giles, Graham G; Spinelli, John J; Chiu, Brian C; Munshi, Nikhil C; Anderson, Kenneth C; Levy, Joan; Zonder, Jeffrey A; Orlowski, Robert Z; Lonial, Sagar; Camp, Nicola J; Vachon, Celine M; Ziv, Elad; Stram, Daniel O; Hazelett, Dennis J; Haiman, Christopher A; Cozen, Wendy

    2016-12-01

    Genome-wide association studies (GWAS) in European populations have identified genetic risk variants associated with multiple myeloma. We performed association testing of common variation in eight regions in 1,318 patients with multiple myeloma and 1,480 controls of European ancestry and 1,305 patients with multiple myeloma and 7,078 controls of African ancestry and conducted a meta-analysis to localize the signals, with epigenetic annotation used to predict functionality. We found that variants in 7p15.3, 17p11.2, 22q13.1 were statistically significantly (P ancestry and persons of European ancestry, and the variant in 3p22.1 was associated in European ancestry only. In a combined African ancestry-European ancestry meta-analysis, variation in five regions (2p23.3, 3p22.1, 7p15.3, 17p11.2, 22q13.1) was statistically significantly associated with multiple myeloma risk. In 3p22.1, the correlated variants clustered within the gene body of ULK4 Correlated variants in 7p15.3 clustered around an enhancer at the 3' end of the CDCA7L transcription termination site. A missense variant at 17p11.2 (rs34562254, Pro251Leu, OR, 1.32; P = 2.93 × 10 -7 ) in TNFRSF13B encodes a lymphocyte-specific protein in the TNF receptor family that interacts with the NF-κB pathway. SNPs correlated with the index signal in 22q13.1 cluster around the promoter and enhancer regions of CBX7 CONCLUSIONS: We found that reported multiple myeloma susceptibility regions contain risk variants important across populations, supporting the use of multiple racial/ethnic groups with different underlying genetic architecture to enhance the localization and identification of putatively functional alleles. A subset of reported risk loci for multiple myeloma has consistent effects across populations and is likely to be functional. Cancer Epidemiol Biomarkers Prev; 25(12); 1609-18. ©2016 AACR. ©2016 American Association for Cancer Research.

  16. Chiral separation and chemical profile of Dengzhan Shengmai by integrating comprehensive with multiple heart-cutting two-dimensional liquid chromatography coupled with quadrupole time-of-flight mass spectrometry.

    Sheng, Ning; Zheng, Hao; Xiao, Yao; Wang, Zhe; Li, Menglin; Zhang, Jinlan

    2017-09-29

    Chemical profile for Chinese medicine formulas composed of several herbs is always a challenge due to a big array of small molecules with high chemical diversity so much as isomers. The present paper develops a feasible strategy to characterize and identify complex chemical constituents of a four-herb traditional Chinese medicine formula, Denzhan Shenmai (DZSM) by integrating comprehensive two-dimensional liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (LC×LC-qTOF-MS) with multiple heart-cutting two-dimensional liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (MHC-qTOF-MS). DZSM was separated by C8×C18 HPLC column system for comprehensive two-dimensional liquid chromatography system and 283 compounds most of which belonged to phenolic acid, flavonoid, saponin and lignan families were characterized and identified within 75min. Some isomers and compounds at low level were analyzed on C8×Chiral HPLC column system for multiple heart-cutting two-dimensional liquid chromatography system with 1D and 2D optimized gradient elution program. These 1D cutting fractions were successively separated on 2D chiral chromatographic column under extended the 2D gradient elution time from 30s to 5.0min. 12 pairs of isomer compounds were separated with good resolution. The combination of LC×LC and MHC system provides a powerful technique for global chemical profiling of DZSM and provided feasible strategy for other complex systems. Copyright © 2017 Elsevier B.V. All rights reserved.

  17. MZDASoft: a software architecture that enables large-scale comparison of protein expression levels over multiple samples based on liquid chromatography/tandem mass spectrometry.

    Ghanat Bari, Mehrab; Ramirez, Nelson; Wang, Zhiwei; Zhang, Jianqiu Michelle

    2015-10-15

    Without accurate peak linking/alignment, only the expression levels of a small percentage of proteins can be compared across multiple samples in Liquid Chromatography/Mass Spectrometry/Tandem Mass Spectrometry (LC/MS/MS) due to the selective nature of tandem MS peptide identification. This greatly hampers biomedical research that aims at finding biomarkers for disease diagnosis, treatment, and the understanding of disease mechanisms. A recent algorithm, PeakLink, has allowed the accurate linking of LC/MS peaks without tandem MS identifications to their corresponding ones with identifications across multiple samples collected from different instruments, tissues and labs, which greatly enhanced the ability of comparing proteins. However, PeakLink cannot be implemented practically for large numbers of samples based on existing software architectures, because it requires access to peak elution profiles from multiple LC/MS/MS samples simultaneously. We propose a new architecture based on parallel processing, which extracts LC/MS peak features, and saves them in database files to enable the implementation of PeakLink for multiple samples. The software has been deployed in High-Performance Computing (HPC) environments. The core part of the software, MZDASoft Parallel Peak Extractor (PPE), can be downloaded with a user and developer's guide, and it can be run on HPC centers directly. The quantification applications, MZDASoft TandemQuant and MZDASoft PeakLink, are written in Matlab, which are compiled with a Matlab runtime compiler. A sample script that incorporates all necessary processing steps of MZDASoft for LC/MS/MS quantification in a parallel processing environment is available. The project webpage is http://compgenomics.utsa.edu/zgroup/MZDASoft. The proposed architecture enables the implementation of PeakLink for multiple samples. Significantly more (100%-500%) proteins can be compared over multiple samples with better quantification accuracy in test cases. MZDASoft

  18. The development and validation of a two-tiered multiple-choice instrument to identify alternative conceptions in earth science

    Mangione, Katherine Anna

    This study was to determine reliability and validity for a two-tiered, multiple- choice instrument designed to identify alternative conceptions in earth science. Additionally, this study sought to identify alternative conceptions in earth science held by preservice teachers, to investigate relationships between self-reported confidence scores and understanding of earth science concepts, and to describe relationships between content knowledge and alternative conceptions and planning instruction in the science classroom. Eighty-seven preservice teachers enrolled in the MAT program participated in this study. Sixty-eight participants were female, twelve were male, and seven chose not to answer. Forty-seven participants were in the elementary certification program, five were in the middle school certification program, and twenty-nine were pursuing secondary certification. Results indicate that the two-tiered, multiple-choice format can be a reliable and valid method for identifying alternative conceptions. Preservice teachers in all certification areas who participated in this study may possess common alternative conceptions previously identified in the literature. Alternative conceptions included: all rivers flow north to south, the shadow of the Earth covers the Moon causing lunar phases, the Sun is always directly overhead at noon, weather can be predicted by animal coverings, and seasons are caused by the Earth's proximity to the Sun. Statistical analyses indicated differences, however not all of them significant, among all subgroups according to gender and certification area. Generally males outperformed females and preservice teachers pursuing middle school certification had higher scores on the questionnaire followed by those obtaining secondary certification. Elementary preservice teachers scored the lowest. Additionally, self-reported scores of confidence in one's answers and understanding of the earth science concept in question were analyzed. There was a

  19. Evaluation of multiple approaches to identify genome-wide polymorphisms in closely related genotypes of sweet cherry (Prunus avium L.

    Seanna Hewitt

    Full Text Available Identification of genetic polymorphisms and subsequent development of molecular markers is important for marker assisted breeding of superior cultivars of economically important species. Sweet cherry (Prunus avium L. is an economically important non-climacteric tree fruit crop in the Rosaceae family and has undergone a genetic bottleneck due to breeding, resulting in limited genetic diversity in the germplasm that is utilized for breeding new cultivars. Therefore, it is critical to recognize the best platforms for identifying genome-wide polymorphisms that can help identify, and consequently preserve, the diversity in a genetically constrained species. For the identification of polymorphisms in five closely related genotypes of sweet cherry, a gel-based approach (TRAP, reduced representation sequencing (TRAPseq, a 6k cherry SNParray, and whole genome sequencing (WGS approaches were evaluated in the identification of genome-wide polymorphisms in sweet cherry cultivars. All platforms facilitated detection of polymorphisms among the genotypes with variable efficiency. In assessing multiple SNP detection platforms, this study has demonstrated that a combination of appropriate approaches is necessary for efficient polymorphism identification, especially between closely related cultivars of a species. The information generated in this study provides a valuable resource for future genetic and genomic studies in sweet cherry, and the insights gained from the evaluation of multiple approaches can be utilized for other closely related species with limited genetic diversity in the breeding germplasm. Keywords: Polymorphisms, Prunus avium, Next-generation sequencing, Target region amplification polymorphism (TRAP, Genetic diversity, SNParray, Reduced representation sequencing, Whole genome sequencing (WGS

  20. Use of gas chromatography-mass spectrometry-olfactometry and a conventional flask test to identify off-flavor compounds generated from phenylalanine during chlorination of drinking water.

    Matsushita, Taku; Sakuma, Miki; Tazawa, Shiori; Hatase, Taiki; Shirasaki, Nobutaka; Matsui, Yoshihiko

    2017-11-15

    Off-flavor in drinking water can be caused by transformation products (TPs) generated from organic compounds, such as amino acids, present during chlorination. However, the contributions of many of these TPs to overall off-flavor have not been quantified, mainly because the lack of appropriate chemical standards prevents sensory evaluation by means of a conventional flask test. In the present study, we used gas chromatography-mass spectrometry-olfactometry (GC-MS-O) to identify compounds responsible for the off-flavor generated by chlorination of an aqueous solution of the amino acid phenylalanine, and we propose a sensory evaluation procedure for quantification of the contributions of the identified TPs to the overall off-flavor, regardless of the availability of chemical standards of the TPs. GC-MS-O revealed that two TPs, N-chlorophenylacetaldimine and 2-chloro-2-phenylacetaldehyde, for which chemical standards are not commercially available, were the main components responsible for the off-flavor of the chlorinated solution. By using a sensory evaluation procedure involving a combination of GC-MS-O and a conventional flask test, we quantified the contributions of TPs to the overall off-flavor of the chlorinated solution. Approximately 60% of the off-flavor was attributable to free chlorine (13%), 2-chloro-2-phenylacetaldehyde (13%), trichloramine (12%) phenylacetaldehyde (11%) phenylacetonitrile (8%), and N-chlorophenylacetaldimine (2%). Treatment with powdered activated carbon (PAC) removed the off-flavor. Experiments with chlorination of 15 N-labeled phenylalanine suggested that PAC reductively decomposed trichloramine into N 2 gas and adsorbed all of the other identified TPs. Superfine PAC (median diameter, 0.7 μm) removed the off-flavor more rapidly than normal-size PAC (median diameter, 8.0 μm). Copyright © 2017 Elsevier Ltd. All rights reserved.

  1. Cross-linking mass spectrometry identifies new interfaces of Augmin required to localise the γ-tubulin ring complex to the mitotic spindle

    Jack W. C. Chen

    2017-05-01

    Full Text Available The hetero-octameric protein complex, Augmin, recruits γ-Tubulin ring complex (γ-TuRC to pre-existing microtubules (MTs to generate branched MTs during mitosis, facilitating robust spindle assembly. However, despite a recent partial reconstitution of the human Augmin complex in vitro, the molecular basis of this recruitment remains unclear. Here, we used immuno-affinity purification of in vivo Augmin from Drosophila and cross-linking/mass spectrometry to identify distance restraints between residues within the eight Augmin subunits in the absence of any other structural information. The results allowed us to predict potential interfaces between Augmin and γ-TuRC. We tested these predictions biochemically and in the Drosophila embryo, demonstrating that specific regions of the Augmin subunits, Dgt3, Dgt5 and Dgt6 all directly bind the γ-TuRC protein, Dgp71WD, and are required for the accumulation of γ-TuRC, but not Augmin, to the mitotic spindle. This study therefore substantially increases our understanding of the molecular mechanisms underpinning MT-dependent MT nucleation.

  2. Profiling analysis of low molecular weight heparins by multiple heart-cutting two dimensional chromatography with quadruple time-of-flight mass spectrometry.

    Ouyang, Yilan; Zeng, Yangyang; Rong, Yinxiu; Song, Yue; Shi, Lv; Chen, Bo; Yang, Xinlei; Xu, Naiyu; Linhardt, Robert J; Zhang, Zhenqing

    2015-09-01

    Low molecular weight heparins (LMWHs) are polydisperse and microheterogenous mixtures of polysaccharides used as anticoagulant drugs. Profiling analysis is important for obtaining deeper insights into the structure of LMWHs. Previous oligosaccharide mapping methods are relatively low resolution and are unable to show an entire picture of the structural complexity of LMWHs. In the current study a profiling method was developed relying on multiple heart-cutting, two-dimensional, ultrahigh performance liquid chromatography with quadruple time-of-flight mass spectrometry. This represents an efficient, automated, and robust approach for profiling LMWHs. Using size-exclusion chromatography and ion-pairing reversed-phase chromatography in a two-dimensional separation, LMW components of different sizes and LMW components of the same size but with different charges and polarities can be resolved, providing a more complete picture of a LMWH. Structural information on each component was then obtained with quadrupole time-of-flight mass spectrometry. More than 80 and 120 oligosaccharides were observed and unambiguously assigned from the LMWHs, nadroparin and enoxaparin, respectively. This method might be useful for quality control of LMWHs and as a powerful tool for heparin-related glycomics.

  3. Histogram analysis parameters identify multiple associations between DWI and DCE MRI in head and neck squamous cell carcinoma.

    Meyer, Hans Jonas; Leifels, Leonard; Schob, Stefan; Garnov, Nikita; Surov, Alexey

    2018-01-01

    Nowadays, multiparametric investigations of head and neck squamous cell carcinoma (HNSCC) are established. These approaches can better characterize tumor biology and behavior. Diffusion weighted imaging (DWI) can by means of apparent diffusion coefficient (ADC) quantitatively characterize different tissue compartments. Dynamic contrast-enhanced magnetic resonance imaging (DCE MRI) reflects perfusion and vascularization of tissues. Recently, a novel approach of data acquisition, namely histogram analysis of different images is a novel diagnostic approach, which can provide more information of tissue heterogeneity. The purpose of this study was to analyze possible associations between DWI, and DCE parameters derived from histogram analysis in patients with HNSCC. Overall, 34 patients, 9 women and 25 men, mean age, 56.7±10.2years, with different HNSCC were involved in the study. DWI was obtained by using of an axial echo planar imaging sequence with b-values of 0 and 800s/mm 2 . Dynamic T1w DCE sequence after intravenous application of contrast medium was performed for estimation of the following perfusion parameters: volume transfer constant (K trans ), volume of the extravascular extracellular leakage space (Ve), and diffusion of contrast medium from the extravascular extracellular leakage space back to the plasma (Kep). Both ADC and perfusion parameters maps were processed offline in DICOM format with custom-made Matlab-based application. Thereafter, polygonal ROIs were manually drawn on the transferred maps on each slice. For every parameter, mean, maximal, minimal, and median values, as well percentiles 10th, 25th, 75th, 90th, kurtosis, skewness, and entropy were estimated. Сorrelation analysis identified multiple statistically significant correlations between the investigated parameters. Ve related parameters correlated well with different ADC values. Especially, percentiles 10 and 75, mode, and median values showed stronger correlations in comparison to other

  4. Prognostic index to identify patients who may not benefit from whole brain radiotherapy for multiple brain metastases from lung cancer

    Sundaresan, P.; Yeghiaian, R.; Gebski, V.

    2010-01-01

    Full text: Palliative whole brain radiotherapy (WBRT) is often recommended in the management of multiple brain metastases. Allowing for WBRT waiting time, duration of the WBRT course and time to clinical response, it may take 6 weeks from the point of initial assessment for a benefit from WBRT to manifest. Patients who die within 6 weeks ('early death') may not benefit from WBRT and may instead experience a decline in quality of life. This study aimed to develop a prognostic index (PI) that identifies the subset of patients with lung cancer with multiple brain metastases who may not benefit from WBRT because of'early death'. The medical records of patients with lung cancer who had WBRT recommended for multiple brain metastases over a 10-year period were retrospectively reviewed. Patients were classified as either having died within 6 weeks or having lived beyond 6 weeks. Potential prognostic indicators were evaluated for correlation with 'early death'. A PI was constructed by modelling the survival classification to determine the contribution of these factors towards shortened survival. Of the 275 patients recommended WBRT, 64 (23.22%) died within 6 weeks. The main prognostic factor predicting early death was Eastern Cooperative Oncology Group (ECOG) status >2. Patients with a high PI score (>13) were at higher risk of'early death'. Twenty-three per cent of patients died prior to benefit from WBRT. ECOG status was the most predictive for 'early death'. Other factors may also contribute towards a poor outcome. With further refinement and validation, the PI could be a valuable clinical decision tool.

  5. ICP magnetic sector multiple collector mass spectrometry and the precise measurement of isotopic compositions using nebulization of solutions and laser ablation of solids

    Halliday, A.N.; Lee, D-C.; Christensen, J.N.; Yi, W.; Hall, C.M.; Jones, C.E.; Teagle, D.A.H.; Freedman, P.A.

    1996-01-01

    Inductively-coupled plasma (ICP) sources offer considerable advantages over thermal sources because the high ionization efficiency facilitates measurements of relatively high sensitivity for elements such as Hf or Sn, which can be difficult to measure precisely with thermal ionization mass spectrometry (TIMS). The mass discrimination (bias) is larger than for TIMS, favours the heavier ions, and decreases in magnitude with increasing mass. However, in contrast to TIMS, this discrimination is largely independent of the chemical or physical properties of the element or the duration of the analysis. This has been demonstrated to high precision with a double focussing multiple collector magnetic sector mass spectrometer with an ICP source. The principle of this instrument is briefly described. The potential of the instrument for high precision isotopic measurements of a very broad range of elements, using solution aspiration or laser ablation, is indicated. 15 refs

  6. Multiple analyte adduct formation in liquid chromatography-tandem mass spectrometry - Advantages and limitations in the analysis of biologically-related samples.

    Dziadosz, Marek

    2018-05-01

    Multiple analyte adduct formation was examined and discussed in the context of reproducible signal detection in liquid chromatography-tandem mass spectrometry applied in the analysis of biologically-related samples. Appropriate infusion solutions were prepared in H 2 O/methanol (3/97, v/v) with 1 mM sodium acetate and 10 mM acetic acid. An API 4000 QTrap tandem mass spectrometer was used for experiments performed in the negative scan mode (-Q1 MS) and the negative enhanced product ion mode (-EPI). γ‑Hydroxybutyrate and its deuterated form were used as model compounds to highlight both the complexity of adduct formation in popular mobile phases used and the effective signal compensation by the application of isotope-labelled analytes as internal standards. Copyright © 2018 Elsevier B.V. All rights reserved.

  7. Fine-mapping identifies multiple prostate cancer risk loci at 5p15, one of which associates with TERT expression

    Kote-Jarai, Zsofia; Saunders, Edward J.; Leongamornlert, Daniel A.; Tymrakiewicz, Malgorzata; Dadaev, Tokhir; Jugurnauth-Little, Sarah; Ross-Adams, Helen; Al Olama, Ali Amin; Benlloch, Sara; Halim, Silvia; Russel, Roslin; Dunning, Alison M.; Luccarini, Craig; Dennis, Joe; Neal, David E.; Hamdy, Freddie C.; Donovan, Jenny L.; Muir, Ken; Giles, Graham G.; Severi, Gianluca; Wiklund, Fredrik; Gronberg, Henrik; Haiman, Christopher A.; Schumacher, Fredrick; Henderson, Brian E.; Le Marchand, Loic; Lindstrom, Sara; Kraft, Peter; Hunter, David J.; Gapstur, Susan; Chanock, Stephen; Berndt, Sonja I.; Albanes, Demetrius; Andriole, Gerald; Schleutker, Johanna; Weischer, Maren; Canzian, Federico; Riboli, Elio; Key, Tim J.; Travis, Ruth C.; Campa, Daniele; Ingles, Sue A.; John, Esther M.; Hayes, Richard B.; Pharoah, Paul; Khaw, Kay-Tee; Stanford, Janet L.; Ostrander, Elaine A.; Signorello, Lisa B.; Thibodeau, Stephen N.; Schaid, Dan; Maier, Christiane; Vogel, Walther; Kibel, Adam S.; Cybulski, Cezary; Lubinski, Jan; Cannon-Albright, Lisa; Brenner, Hermann; Park, Jong Y.; Kaneva, Radka; Batra, Jyotsna; Spurdle, Amanda; Clements, Judith A.; Teixeira, Manuel R.; Govindasami, Koveela; Guy, Michelle; Wilkinson, Rosemary A.; Sawyer, Emma J.; Morgan, Angela; Dicks, Ed; Baynes, Caroline; Conroy, Don; Bojesen, Stig E.; Kaaks, Rudolf; Vincent, Daniel; Bacot, François; Tessier, Daniel C.; Easton, Douglas F.; Eeles, Rosalind A.

    2013-01-01

    Associations between single nucleotide polymorphisms (SNPs) at 5p15 and multiple cancer types have been reported. We have previously shown evidence for a strong association between prostate cancer (PrCa) risk and rs2242652 at 5p15, intronic in the telomerase reverse transcriptase (TERT) gene that encodes TERT. To comprehensively evaluate the association between genetic variation across this region and PrCa, we performed a fine-mapping analysis by genotyping 134 SNPs using a custom Illumina iSelect array or Sequenom MassArray iPlex, followed by imputation of 1094 SNPs in 22 301 PrCa cases and 22 320 controls in The PRACTICAL consortium. Multiple stepwise logistic regression analysis identified four signals in the promoter or intronic regions of TERT that independently associated with PrCa risk. Gene expression analysis of normal prostate tissue showed evidence that SNPs within one of these regions also associated with TERT expression, providing a potential mechanism for predisposition to disease. PMID:23535824

  8. APPLICATION OF MULTIPLE LOGISTIC REGRESSION, BAYESIAN LOGISTIC AND CLASSIFICATION TREE TO IDENTIFY THE SIGNIFICANT FACTORS INFLUENCING CRASH SEVERITY

    MILAD TAZIK

    2017-11-01

    Full Text Available Identifying cases in which road crashes result in fatality or injury of drivers may help improve their safety. In this study, datasets of crashes happened in TehranQom freeway, Iran, were examined by three models (multiple logistic regression, Bayesian logistic and classification tree to analyse the contribution of several variables to fatal accidents. For multiple logistic regression and Bayesian logistic models, the odds ratio was calculated for each variable. The model which best suited the identification of accident severity was determined based on AIC and DIC criteria. Based on the results of these two models, rollover crashes (OR = 14.58, %95 CI: 6.8-28.6, not using of seat belt (OR = 5.79, %95 CI: 3.1-9.9, exceeding speed limits (OR = 4.02, %95 CI: 1.8-7.9 and being female (OR = 2.91, %95 CI: 1.1-6.1 were the most important factors in fatalities of drivers. In addition, the results of the classification tree model have verified the findings of the other models.

  9. Tandem mass spectrometry, but not T-cell receptor excision circle analysis, identifies newborns with late-onset adenosine deaminase deficiency.

    la Marca, Giancarlo; Canessa, Clementina; Giocaliere, Elisa; Romano, Francesca; Duse, Marzia; Malvagia, Sabrina; Lippi, Francesca; Funghini, Silvia; Bianchi, Leila; Della Bona, Maria Luisa; Valleriani, Claudia; Ombrone, Daniela; Moriondo, Maria; Villanelli, Fabio; Speckmann, Carsten; Adams, Stuart; Gaspar, Bobby H; Hershfield, Michael; Santisteban, Ines; Fairbanks, Lynette; Ragusa, Giovanni; Resti, Massimo; de Martino, Maurizio; Guerrini, Renzo; Azzari, Chiara

    2013-06-01

    Adenosine deaminase (ADA)-severe combined immunodeficiency (SCID) is caused by genetic variants that disrupt the function of ADA. In its early-onset form, it is rapidly fatal to infants. Delayed or late-onset ADA-SCID is characterized by insidious progressive immunodeficiency that leads to permanent organ damage or death. Quantification of T-cell receptor excision circles (TRECs) or tandem mass spectrometry (tandem-MS) analysis of dried blood spots (DBSs) collected at birth can identify newborns with early-onset ADA-SCID and are used in screening programs. However, it is not clear whether these analyses can identify newborns who will have delayed or late-onset ADA-SCID before symptoms appear. We performed a retrospective study to evaluate whether tandem-MS and quantitative TREC analyses of DBSs could identify newborns who had delayed-onset ADA-SCID later in life. We tested stored DBSs collected at birth from 3 patients with delayed-onset ADA-SCID using tandem-MS (PCT EP2010/070517) to evaluate levels of adenosine and 2'-deoxyadenosine and real-time PCR to quantify TREC levels. We also analyzed DBSs from 3 newborns with early-onset ADA-SCID and 2 healthy newborn carriers of ADA deficiency. The DBSs taken at birth from the 3 patients with delayed-onset ADA-SCID had adenosine levels of 10, 25, and 19 μmol/L (normal value, <1.5 μmol/L) and 2'-deoxyadenosine levels of 0.7, 2.7, and 2.4 μmol/L (normal value, <0.07 μmol/L); the mean levels of adenosine and 2'-deoxyadenosine were respectively 12.0- and 27.6-fold higher than normal values. DBSs taken at birth from all 3 patients with delayed-onset ADA deficiency had normal TREC levels, but TRECs were undetectable in blood samples taken from the same patients at the time of diagnosis. Tandem-MS but not TREC quantification identifies newborns with delayed- or late-onset ADA deficiency. Copyright © 2013 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.

  10. Identifying location and severity of multiple cracks in reinforced concrete cantilever beams using modal and wavelet analysis

    Tahere Arefzade

    2016-06-01

    Full Text Available In this paper, a method of multiple cracks detection in a cantilever reinforced concrete beam based on wavelet transform is presented. For this purpose, different damage scenarios in concrete beam were considered. Then, the four first mode shapes of undamaged and damaged beam using ABAQUS software were extracted. The estimated mode shapes of the beam are analyzed by the continuous and discrete wavelet transform (CWT & DWT to detect the damage scenarios. It was found that DWT is more sensitive to damage location than CWT in the concrete beam which introduced in this paper. Also, the influence of the mode order and the effect of damage distance from support on the effectiveness of damage detection was evaluated. It was observed that the distance of cracks to each other have no effect on identifying their location.

  11. In silico analysis to identify vaccine candidates common to multiple serotypes of Shigella and evaluation of their immunogenicity

    Pahil, Sapna

    2017-08-02

    Shigellosis or bacillary dysentery is an important cause of diarrhea, with the majority of the cases occurring in developing countries. Considering the high disease burden, increasing antibiotic resistance, serotype-specific immunity and the post-infectious sequelae associated with shigellosis, there is a pressing need of an effective vaccine against multiple serotypes of the pathogen. In the present study, we used bio-informatics approach to identify antigens shared among multiple serotypes of Shigella spp. This approach led to the identification of many immunogenic peptides. The five most promising peptides based on MHC binding efficiency were a putative lipoprotein (EL PGI I), a putative heat shock protein (EL PGI II), Spa32 (EL PGI III), IcsB (EL PGI IV) and a hypothetical protein (EL PGI V). These peptides were synthesized and the immunogenicity was evaluated in BALB/c mice by ELISA and cytokine assays. The putative heat shock protein (HSP) and the hypothetical protein elicited good humoral response, whereas putative lipoprotein, Spa32 and IcsB elicited good T-cell response as revealed by increased IFN-γ and TNF-α cytokine levels. The patient sera from confirmed cases of shigellosis were also evaluated for the presence of peptide specific antibodies with significant IgG and IgA antibodies against the HSP and the hypothetical protein, bestowing them as potential future vaccine candidates. The antigens reported in this study are novel and have not been tested as vaccine candidates against Shigella. This study offers time and cost-effective way of identifying unprecedented immunogenic antigens to be used as potential vaccine candidates. Moreover, this approach should easily be extendable to find new potential vaccine candidates for other pathogenic bacteria.

  12. In silico analysis to identify vaccine candidates common to multiple serotypes of Shigella and evaluation of their immunogenicity

    Pahil, Sapna; Taneja, Neelam; Ansari, Hifzur Rahman; Raghava, G. P. S.

    2017-01-01

    Shigellosis or bacillary dysentery is an important cause of diarrhea, with the majority of the cases occurring in developing countries. Considering the high disease burden, increasing antibiotic resistance, serotype-specific immunity and the post-infectious sequelae associated with shigellosis, there is a pressing need of an effective vaccine against multiple serotypes of the pathogen. In the present study, we used bio-informatics approach to identify antigens shared among multiple serotypes of Shigella spp. This approach led to the identification of many immunogenic peptides. The five most promising peptides based on MHC binding efficiency were a putative lipoprotein (EL PGI I), a putative heat shock protein (EL PGI II), Spa32 (EL PGI III), IcsB (EL PGI IV) and a hypothetical protein (EL PGI V). These peptides were synthesized and the immunogenicity was evaluated in BALB/c mice by ELISA and cytokine assays. The putative heat shock protein (HSP) and the hypothetical protein elicited good humoral response, whereas putative lipoprotein, Spa32 and IcsB elicited good T-cell response as revealed by increased IFN-γ and TNF-α cytokine levels. The patient sera from confirmed cases of shigellosis were also evaluated for the presence of peptide specific antibodies with significant IgG and IgA antibodies against the HSP and the hypothetical protein, bestowing them as potential future vaccine candidates. The antigens reported in this study are novel and have not been tested as vaccine candidates against Shigella. This study offers time and cost-effective way of identifying unprecedented immunogenic antigens to be used as potential vaccine candidates. Moreover, this approach should easily be extendable to find new potential vaccine candidates for other pathogenic bacteria.

  13. In silico analysis to identify vaccine candidates common to multiple serotypes of Shigella and evaluation of their immunogenicity.

    Pahil, Sapna; Taneja, Neelam; Ansari, Hifzur Rahman; Raghava, G P S

    2017-01-01

    Shigellosis or bacillary dysentery is an important cause of diarrhea, with the majority of the cases occurring in developing countries. Considering the high disease burden, increasing antibiotic resistance, serotype-specific immunity and the post-infectious sequelae associated with shigellosis, there is a pressing need of an effective vaccine against multiple serotypes of the pathogen. In the present study, we used bio-informatics approach to identify antigens shared among multiple serotypes of Shigella spp. This approach led to the identification of many immunogenic peptides. The five most promising peptides based on MHC binding efficiency were a putative lipoprotein (EL PGI I), a putative heat shock protein (EL PGI II), Spa32 (EL PGI III), IcsB (EL PGI IV) and a hypothetical protein (EL PGI V). These peptides were synthesized and the immunogenicity was evaluated in BALB/c mice by ELISA and cytokine assays. The putative heat shock protein (HSP) and the hypothetical protein elicited good humoral response, whereas putative lipoprotein, Spa32 and IcsB elicited good T-cell response as revealed by increased IFN-γ and TNF-α cytokine levels. The patient sera from confirmed cases of shigellosis were also evaluated for the presence of peptide specific antibodies with significant IgG and IgA antibodies against the HSP and the hypothetical protein, bestowing them as potential future vaccine candidates. The antigens reported in this study are novel and have not been tested as vaccine candidates against Shigella. This study offers time and cost-effective way of identifying unprecedented immunogenic antigens to be used as potential vaccine candidates. Moreover, this approach should easily be extendable to find new potential vaccine candidates for other pathogenic bacteria.

  14. In silico analysis to identify vaccine candidates common to multiple serotypes of Shigella and evaluation of their immunogenicity.

    Sapna Pahil

    Full Text Available Shigellosis or bacillary dysentery is an important cause of diarrhea, with the majority of the cases occurring in developing countries. Considering the high disease burden, increasing antibiotic resistance, serotype-specific immunity and the post-infectious sequelae associated with shigellosis, there is a pressing need of an effective vaccine against multiple serotypes of the pathogen. In the present study, we used bio-informatics approach to identify antigens shared among multiple serotypes of Shigella spp. This approach led to the identification of many immunogenic peptides. The five most promising peptides based on MHC binding efficiency were a putative lipoprotein (EL PGI I, a putative heat shock protein (EL PGI II, Spa32 (EL PGI III, IcsB (EL PGI IV and a hypothetical protein (EL PGI V. These peptides were synthesized and the immunogenicity was evaluated in BALB/c mice by ELISA and cytokine assays. The putative heat shock protein (HSP and the hypothetical protein elicited good humoral response, whereas putative lipoprotein, Spa32 and IcsB elicited good T-cell response as revealed by increased IFN-γ and TNF-α cytokine levels. The patient sera from confirmed cases of shigellosis were also evaluated for the presence of peptide specific antibodies with significant IgG and IgA antibodies against the HSP and the hypothetical protein, bestowing them as potential future vaccine candidates. The antigens reported in this study are novel and have not been tested as vaccine candidates against Shigella. This study offers time and cost-effective way of identifying unprecedented immunogenic antigens to be used as potential vaccine candidates. Moreover, this approach should easily be extendable to find new potential vaccine candidates for other pathogenic bacteria.

  15. Quantitative Isotope-Dilution High-Resolution-Mass-Spectrometry Analysis of Multiple Intracellular Metabolites in Clostridium autoethanogenum with Uniformly 13C-Labeled Standards Derived from Spirulina.

    Schatschneider, Sarah; Abdelrazig, Salah; Safo, Laudina; Henstra, Anne M; Millat, Thomas; Kim, Dong-Hyun; Winzer, Klaus; Minton, Nigel P; Barrett, David A

    2018-04-03

    We have investigated the applicability of commercially available lyophilized spirulina ( Arthrospira platensis), a microorganism uniformly labeled with 13 C, as a readily accessible source of multiple 13 C-labeled metabolites suitable as internal standards for the quantitative determination of intracellular bacterial metabolites. Metabolites of interest were analyzed by hydrophilic-interaction liquid chromatography coupled with high-resolution mass spectrometry. Multiple internal standards obtained from uniformly (U)- 13 C-labeled extracts from spirulina were used to enable isotope-dilution mass spectrometry (IDMS) in the identification and quantification of intracellular metabolites. Extraction of the intracellular metabolites of Clostridium autoethanogenum using 2:1:1 chloroform/methanol/water was found to be the optimal method in comparison with freeze-thaw, homogenization, and sonication methods. The limits of quantification were ≤1 μM with excellent linearity for all of the calibration curves ( R 2 ≥ 0.99) for 74 metabolites. The precision and accuracy were found to be within relative standard deviations (RSDs) of 15% for 49 of the metabolites and within RSDs of 20% for all of the metabolites. The method was applied to study the effects of feeding different levels of carbon monoxide (as a carbon source) on the central metabolism and Wood-Ljungdahl pathway of C. autoethanogenum grown in continuous culture over 35 days. Using LC-IDMS with U- 13 C spirulina allowed the successful quantification of 52 metabolites in the samples, including amino acids, carboxylic acids, sugar phosphates, purines, and pyrimidines. The method provided absolute quantitative data on intracellular metabolites that was suitable for computational modeling to understand and optimize the C. autoethanogenum metabolic pathways active in gas fermentation.

  16. Quantitative analysis of multiple high-resolution mass spectrometry images using chemometric methods: quantitation of chlordecone in mouse liver.

    Mohammadi, Saeedeh; Parastar, Hadi

    2018-05-15

    In this work, a chemometrics-based strategy is developed for quantitative mass spectrometry imaging (MSI). In this regard, quantification of chlordecone as a carcinogenic organochlorinated pesticide (C10Cll0O) in mouse liver using the matrix-assisted laser desorption ionization MSI (MALDI-MSI) method is used as a case study. The MSI datasets corresponded to 1, 5 and 10 days of mouse exposure to the standard chlordecone in the quantity range of 0 to 450 μg g-1. The binning approach in the m/z direction is used to group high resolution m/z values and to reduce the big data size. To consider the effect of bin size on the quality of results, three different bin sizes of 0.25, 0.5 and 1.0 were chosen. Afterwards, three-way MSI data arrays (two spatial and one m/z dimensions) for seven standards and four unknown samples were column-wise augmented with m/z values as the common mode. Then, these datasets were analyzed using multivariate curve resolution-alternating least squares (MCR-ALS) using proper constraints. The resolved mass spectra were used for identification of chlordecone in the presence of a complex background and interference. Additionally, the augmented spatial profiles were post-processed and 2D images for each component were obtained in calibration and unknown samples. The sum of these profiles was utilized to set the calibration curve and to obtain the analytical figures of merit (AFOMs). Inspection of the results showed that the lower bin size (i.e., 0.25) provides more accurate results. Finally, the obtained results by MCR for three datasets were compared with those of gas chromatography-mass spectrometry (GC-MS) and MALDI-MSI. The results showed that the MCR-assisted method gives a higher amount of chlordecone than MALDI-MSI and a lower amount than GC-MS. It is concluded that a combination of chemometric methods with MSI can be considered as an alternative way for MSI quantification.

  17. Simultaneous screening and confirmation of multiple classes of drug residues in fish by liquid chromatography-ion trap mass spectrometry.

    Smith, Shani; Gieseker, Charles; Reimschuessel, Renate; Decker, Christie-Sue; Carson, Mary C

    2009-11-13

    LC-ion trap mass spectrometry was used to screen and confirm 38 compounds from a variety of drug classes in four species of fish: trout, salmon, catfish, and tilapia. Samples were extracted with acetonitrile and hexane. The acetonitrile phase was evaporated, redissolved in water and acetonitrile, and analyzed by gradient chromatography on a phenyl column. MS(2) or MS(3) spectra were monitored for each compound. Qualitative method performance was evaluated by the analysis over several days of replicate samples of control fish, fish fortified with a drug mixture at 1 ppm, 0.1 ppm and 0.01 ppm, and fish dosed with a representative from each drug class. Half of the 38 drugs were confirmed at 0.01 ppm, the lowest fortification level. This included all of the quinolones and fluoroquinolones, the macrolides, malachite green, and most of the imidazoles. Florfenicol amine, metronidazole, sulfonamides, tetracyclines, and most of the betalactams were confirmed at 0.1 ppm. Ivermectin and penicillin G were only detectable in the 1 ppm fortified samples. With the exception of amoxicillin, emamectin, metronidazole, and tylosin, residue presence was confirmed in all the dosed fish.

  18. In silico repositioning-chemogenomics strategy identifies new drugs with potential activity against multiple life stages of Schistosoma mansoni.

    Bruno J Neves

    2015-01-01

    Full Text Available Morbidity and mortality caused by schistosomiasis are serious public health problems in developing countries. Because praziquantel is the only drug in therapeutic use, the risk of drug resistance is a concern. In the search for new schistosomicidal drugs, we performed a target-based chemogenomics screen of a dataset of 2,114 proteins to identify drugs that are approved for clinical use in humans that may be active against multiple life stages of Schistosoma mansoni. Each of these proteins was treated as a potential drug target, and its amino acid sequence was used to interrogate three databases: Therapeutic Target Database (TTD, DrugBank and STITCH. Predicted drug-target interactions were refined using a combination of approaches, including pairwise alignment, conservation state of functional regions and chemical space analysis. To validate our strategy, several drugs previously shown to be active against Schistosoma species were correctly predicted, such as clonazepam, auranofin, nifedipine, and artesunate. We were also able to identify 115 drugs that have not yet been experimentally tested against schistosomes and that require further assessment. Some examples are aprindine, gentamicin, clotrimazole, tetrabenazine, griseofulvin, and cinnarizine. In conclusion, we have developed a systematic and focused computer-aided approach to propose approved drugs that may warrant testing and/or serve as lead compounds for the design of new drugs against schistosomes.

  19. Multiple heart-cutting two dimensional liquid chromatography quadrupole time-of-flight mass spectrometry of pyrrolizidine alkaloids.

    van de Schans, Milou G M; Blokland, Marco H; Zoontjes, Paul W; Mulder, Patrick P J; Nielen, Michel W F

    2017-06-23

    Pyrrolizidine alkaloids (PAs) and their and the corresponding N-oxides (PAs-ox) are genotoxic plant metabolites which can be present as unwanted contaminants in food products of herbal origin like tea and food supplements. PAs and PAs-ox come in a wide variety of molecular structures including many structural isomers. For toxicity assessment it is important to determine the composition of a sample and to resolve all isomeric PAs and PAs-ox, which is currently not possible in one liquid or gas chromatographic (LC or GC) run. In this study an online two dimensional liquid chromatography quadrupole time-of-flight mass spectrometry (2D-LC QToF-MS) method was developed to resolve isomeric PAs and PAs-ox. After comprehensive column and mobile phase selection a polar endcapped C 18 column was used at pH 3 in the first dimension, and a cross-linked C 18 column at pH 10 in the second dimension. Injection solvents, column IDs, flow rates and temperatures were carefully optimized. The method with column selection valve switching described in this study was able to resolve and visualize 20 individual PAs/PAs-ox (6 sets of isomers) in one 2D-LC QToF-MS run. Moreover, it was shown that all isomeric PAs/PAs-ox could be unambiguously annotated. The method was shown to be applicable for the determination and quantification of isomeric PAs/PAs-ox in plant extracts and could be easily extended to include other PAs and PAs-ox. Copyright © 2017 Elsevier B.V. All rights reserved.

  20. The ability of clinical balance measures to identify falls risk in multiple sclerosis: a systematic review and meta-analysis.

    Quinn, Gillian; Comber, Laura; Galvin, Rose; Coote, Susan

    2018-05-01

    To determine the ability of clinical measures of balance to distinguish fallers from non-fallers and to determine their predictive validity in identifying those at risk of falls. AMED, CINAHL, Medline, Scopus, PubMed Central and Google Scholar. First search: July 2015. Final search: October 2017. Inclusion criteria were studies of adults with a definite multiple sclerosis diagnosis, a clinical balance assessment and method of falls recording. Data were extracted independently by two reviewers. Study quality was assessed using the Quality Assessment of Diagnostic Accuracy Studies-2 scale and the modified Newcastle-Ottawa Quality Assessment Scale. Statistical analysis was conducted for the cross-sectional studies using Review Manager 5. The mean difference with 95% confidence interval in balance outcomes between fallers and non-fallers was used as the mode of analysis. We included 33 studies (19 cross-sectional, 5 randomised controlled trials, 9 prospective) with a total of 3901 participants, of which 1917 (49%) were classified as fallers. The balance measures most commonly reported were the Berg Balance Scale, Timed Up and Go and Falls Efficacy Scale International. Meta-analysis demonstrated fallers perform significantly worse than non-fallers on all measures analysed except the Timed Up and Go Cognitive ( p Balance Confidence Scale had the highest area under the receiver operating characteristic curve value (0.92), but without reporting corresponding measures of clinical utility. Clinical measures of balance differ significantly between fallers and non-fallers but have poor predictive ability for falls risk in people with multiple sclerosis.

  1. Clinical significance of coryneform Gram-positive rods from blood identified by MALDI-TOF mass spectrometry and their susceptibility profiles - a retrospective chart review.

    Mushtaq, Ammara; Chen, Derrick J; Strand, Gregory J; Dylla, Brenda L; Cole, Nicolynn C; Mandrekar, Jayawant; Patel, Robin

    2016-07-01

    With the advent of matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS), most Gram-positive rods (GPRs) are readily identified; however, their clinical relevance in blood cultures remains unclear. Herein, we assessed the clinical significance of GPRs isolated from blood and identified in the era of MALDI-TOF MS. A retrospective chart review of patients presenting to the Mayo Clinic, Rochester, MN, from January 1, 2013, to October 13, 2015, was performed. Any episode of a positive blood culture for a GPR was included. We assessed the number of bottles positive for a given isolate, time to positivity of blood cultures, patient age, medical history, interpretation of culture results by the healthcare team and whether infectious diseases consultation was obtained. We also evaluated the susceptibility profiles of a larger collection of GPRs tested in the clinical microbiology laboratory of the Mayo Clinic, Rochester, MN from January 1, 2013, to October 31, 2015. There were a total of 246 GPRs isolated from the blood of 181 patients during the study period. 56% (n = 101) were deemed contaminants by the healthcare team and were not treated; 33% (n = 59) were clinically determined to represent true bacteremia and were treated; and 8% (n = 14) were considered of uncertain significance, with patients prescribed treatment regardless. Patient characteristics associated with an isolate being treated on univariate analysis included younger age (P = 0.02), identification to the species level (P = 0.02), higher number of positive blood culture sets (P < 0.0001), lower time to positivity (P < 0.0001), immunosuppression (P = 0.03), and recommendation made by an infectious disease consultant (P = 0.0005). On multivariable analysis, infectious diseases consultation (P = 0.03), higher number of positive blood culture sets (P = 0.0005) and lower time to positivity (P = 0.03) were associated with an isolate being treated. 100, 83, 48 and 34% of GPRs

  2. In house validation of a high resolution mass spectrometry Orbitrap-based method for multiple allergen detection in a processed model food.

    Pilolli, Rosa; De Angelis, Elisabetta; Monaci, Linda

    2018-02-13

    In recent years, mass spectrometry (MS) has been establishing its role in the development of analytical methods for multiple allergen detection, but most analyses are being carried out on low-resolution mass spectrometers such as triple quadrupole or ion traps. In this investigation, performance provided by a high resolution (HR) hybrid quadrupole-Orbitrap™ MS platform for the multiple allergens detection in processed food matrix is presented. In particular, three different acquisition modes were compared: full-MS, targeted-selected ion monitoring with data-dependent fragmentation (t-SIM/dd2), and parallel reaction monitoring. In order to challenge the HR-MS platform, the sample preparation was kept as simple as possible, limited to a 30-min ultrasound-aided protein extraction followed by clean-up with disposable size exclusion cartridges. Selected peptide markers tracing for five allergenic ingredients namely skim milk, whole egg, soy flour, ground hazelnut, and ground peanut were monitored in home-made cookies chosen as model processed matrix. Timed t-SIM/dd2 was found the best choice as a good compromise between sensitivity and accuracy, accomplishing the detection of 17 peptides originating from the five allergens in the same run. The optimized method was validated in-house through the evaluation of matrix and processing effects, recoveries, and precision. The selected quantitative markers for each allergenic ingredient provided quantification of 60-100 μg ingred /g allergenic ingredient/matrix in incurred cookies.

  3. The Multimorbidity Cluster Analysis Tool: Identifying Combinations and Permutations of Multiple Chronic Diseases Using a Record-Level Computational Analysis

    Kathryn Nicholson

    2017-12-01

    Full Text Available Introduction: Multimorbidity, or the co-occurrence of multiple chronic health conditions within an individual, is an increasingly dominant presence and burden in modern health care systems.  To fully capture its complexity, further research is needed to uncover the patterns and consequences of these co-occurring health states.  As such, the Multimorbidity Cluster Analysis Tool and the accompanying Multimorbidity Cluster Analysis Toolkit have been created to allow researchers to identify distinct clusters that exist within a sample of participants or patients living with multimorbidity.  Development: The Tool and Toolkit were developed at Western University in London, Ontario, Canada.  This open-access computational program (JAVA code and executable file was developed and tested to support an analysis of thousands of individual records and up to 100 disease diagnoses or categories.  Application: The computational program can be adapted to the methodological elements of a research project, including type of data, type of chronic disease reporting, measurement of multimorbidity, sample size and research setting.  The computational program will identify all existing, and mutually exclusive, combinations and permutations within the dataset.  An application of this computational program is provided as an example, in which more than 75,000 individual records and 20 chronic disease categories resulted in the detection of 10,411 unique combinations and 24,647 unique permutations among female and male patients.  Discussion: The Tool and Toolkit are now available for use by researchers interested in exploring the complexities of multimorbidity.  Its careful use, and the comparison between results, will be valuable additions to the nuanced understanding of multimorbidity.

  4. Newly Identified Gait Patterns in Patients With Multiple Sclerosis May Be Related to Push-off Quality.

    Kempen, Jiska C E; Doorenbosch, Caroline A M; Knol, Dirk L; de Groot, Vincent; Beckerman, Heleen

    2016-11-01

    Limited walking ability is an important problem for patients with multiple sclerosis. A better understanding of how gait impairments lead to limited walking ability may help to develop more targeted interventions. Although gait classifications are available in cerebral palsy and stroke, relevant knowledge in MS is scarce. The aims of this study were: (1) to identify distinctive gait patterns in patients with MS based on a combined evaluation of kinematics, gait features, and muscle activity during walking and (2) to determine the clinical relevance of these gait patterns. This was a cross-sectional study of 81 patients with MS of mild-to-moderate severity (Expanded Disability Status Scale [EDSS] median score=3.0, range=1.0-7.0) and an age range of 28 to 69 years. The patients participated in 2-dimensional video gait analysis, with concurrent measurement of surface electromyography and ground reaction forces. A score chart of 73 gait items was used to rate each gait analysis. A single rater performed the scoring. Latent class analysis was used to identify gait classes. Analysis of the 73 gait variables revealed that 9 variables could distinguish 3 clinically meaningful gait classes. The 9 variables were: (1) heel-rise in terminal stance, (2) push-off, (3) clearance in initial swing, (4) plantar-flexion position in mid-swing, (5) pelvic rotation, (6) arm-trunk movement, (7) activity of the gastrocnemius muscle in pre-swing, (8) M-wave, and (9) propulsive force. The EDSS score and gait speed worsened in ascending classes. Most participants had mild-to-moderate limitations in walking ability based on their EDSS scores, and the number of walkers who were severely limited was small. Based on a small set of 9 variables measured with 2-dimensional clinical gait analysis, patients with MS could be divided into 3 different gait classes. The gait variables are suggestive of insufficient ankle push-off. © 2016 American Physical Therapy Association.

  5. Metabolomic approach to human brain spectroscopy identifies associations between clinical features and the frontal lobe metabolome in multiple sclerosis

    Vingara, Lisa K.; Yu, Hui Jing; Wagshul, Mark E.; Serafin, Dana; Christodoulou, Christopher; Pelczer, István; Krupp, Lauren B.; Maletić-Savatić, Mirjana

    2013-01-01

    Proton magnetic resonance spectroscopy (1H-MRS) is capable of noninvasively detecting metabolic changes that occur in the brain tissue in vivo. Its clinical utility has been limited so far, however, by analytic methods that focus on independently evaluated metabolites and require prior knowledge about which metabolites to examine. Here, we applied advanced computational methodologies from the field of metabolomics, specifically partial least squares discriminant analysis and orthogonal partial least squares, to in vivo 1H-MRS from frontal lobe white matter of 27 patients with relapsing–remitting multiple sclerosis (RRMS) and 14 healthy controls. We chose RRMS, a chronic demyelinating disorder of the central nervous system, because its complex pathology and variable disease course make the need for reliable biomarkers of disease progression more pressing. We show that in vivo MRS data, when analyzed by multivariate statistical methods, can provide reliable, distinct profiles of MRS-detectable metabolites in different patient populations. Specifically, we find that brain tissue in RRMS patients deviates significantly in its metabolic profile from that of healthy controls, even though it appears normal by standard MRI techniques. We also identify, using statistical means, the metabolic signatures of certain clinical features common in RRMS, such as disability score, cognitive impairments, and response to stress. This approach to human in vivo MRS data should promote understanding of the specific metabolic changes accompanying disease pathogenesis, and could provide biomarkers of disease progression that would be useful in clinical trials. PMID:23751863

  6. Determination of multiple pesticides in fruits and vegetables using a modified quick, easy, cheap, effective, rugged and safe method with magnetic nanoparticles and gas chromatography tandem mass spectrometry.

    Li, Yan-Fei; Qiao, Lu-Qin; Li, Fang-Wei; Ding, Yi; Yang, Zi-Jun; Wang, Ming-Lin

    2014-09-26

    Based on a modified quick, easy, cheap, effective, rugged and safe (QuEChERS) sample preparation method with Fe3O4 magnetic nanoparticles (MNPs) as the adsorbing material and gas chromatography-tandem mass spectrometry (GC-MS/MS) determination in multiple reaction monitoring (MRM) mode, we established a new method for the determination of multiple pesticides in vegetables and fruits. It was determined that bare MNPs have excellent function as adsorbent when purified, and it is better to be separated from the extract. The amount of MNPs influenced the clean-up performance and recoveries. To achieve the optimum performance of modified QuEChERS towards the target analytes, several parameters including the amount of the adsorbents and purification time were investigated. Under the optimum conditions, recoveries were evaluated in four representative matrices (tomato, cucumber, orange and apple) with the spiked concentrations of 10 μg kg(-1), 50 μg kg(-1)and 200 μg kg(-1) in all cases. The results showed that the recovery of 101 pesticides ranged between 71.5 and 111.7%, and the relative standard deviation was less than 10.5%. The optimum clean-up system improved the purification efficiency and simultaneously obtained satisfactory recoveries of multiple pesticides, including planar-ring pesticides. In short, the modified QuEChERS method in addition to MNPs used for removing impurities improved the speed of sample pre-treatment and exhibited an enhanced performance and purifying effect. Copyright © 2014 Elsevier B.V. All rights reserved.

  7. A method for determining the analytical form of a radionuclide depth distribution using multiple gamma spectrometry measurements

    Dewey, Steven Clifford, E-mail: sdewey001@gmail.com [United States Air Force School of Aerospace Medicine, Occupational Environmental Health Division, Health Physics Branch, Radiation Analysis Laboratories, 2350 Gillingham Drive, Brooks City-Base, TX 78235 (United States); Whetstone, Zachary David, E-mail: zacwhets@umich.edu [Radiological Health Engineering Laboratory, Department of Nuclear Engineering and Radiological Sciences, University of Michigan, 2355 Bonisteel Boulevard, 1906 Cooley Building, Ann Arbor, MI 48109-2104 (United States); Kearfott, Kimberlee Jane, E-mail: kearfott@umich.edu [Radiological Health Engineering Laboratory, Department of Nuclear Engineering and Radiological Sciences, University of Michigan, 2355 Bonisteel Boulevard, 1906 Cooley Building, Ann Arbor, MI 48109-2104 (United States)

    2011-06-15

    When characterizing environmental radioactivity, whether in the soil or within concrete building structures undergoing remediation or decommissioning, it is highly desirable to know the radionuclide depth distribution. This is typically modeled using continuous analytical expressions, whose forms are believed to best represent the true source distributions. In situ gamma ray spectroscopic measurements are combined with these models to fully describe the source. Currently, the choice of analytical expressions is based upon prior experimental core sampling results at similar locations, any known site history, or radionuclide transport models. This paper presents a method, employing multiple in situ measurements at a single site, for determining the analytical form that best represents the true depth distribution present. The measurements can be made using a variety of geometries, each of which has a different sensitivity variation with source spatial distribution. Using non-linear least squares numerical optimization methods, the results can be fit to a collection of analytical models and the parameters of each model determined. The analytical expression that results in the fit with the lowest residual is selected as the most accurate representation. A cursory examination is made of the effects of measurement errors on the method. - Highlights: > A new method for determining radionuclide distribution as a function of depth is presented. > Multiple measurements are used, with enough measurements to determine the unknowns in analytical functions that might describe the distribution. > The measurements must be as independent as possible, which is achieved through special collimation of the detector. > Although the effects of measurements errors may be significant on the results, an improvement over other methods is anticipated.

  8. Fine-scale mapping of 8q24 locus identifies multiple independent risk variants for breast cancer.

    Shi, Jiajun; Zhang, Yanfeng; Zheng, Wei; Michailidou, Kyriaki; Ghoussaini, Maya; Bolla, Manjeet K; Wang, Qin; Dennis, Joe; Lush, Michael; Milne, Roger L; Shu, Xiao-Ou; Beesley, Jonathan; Kar, Siddhartha; Andrulis, Irene L; Anton-Culver, Hoda; Arndt, Volker; Beckmann, Matthias W; Zhao, Zhiguo; Guo, Xingyi; Benitez, Javier; Beeghly-Fadiel, Alicia; Blot, William; Bogdanova, Natalia V; Bojesen, Stig E; Brauch, Hiltrud; Brenner, Hermann; Brinton, Louise; Broeks, Annegien; Brüning, Thomas; Burwinkel, Barbara; Cai, Hui; Canisius, Sander; Chang-Claude, Jenny; Choi, Ji-Yeob; Couch, Fergus J; Cox, Angela; Cross, Simon S; Czene, Kamila; Darabi, Hatef; Devilee, Peter; Droit, Arnaud; Dork, Thilo; Fasching, Peter A; Fletcher, Olivia; Flyger, Henrik; Fostira, Florentia; Gaborieau, Valerie; García-Closas, Montserrat; Giles, Graham G; Guenel, Pascal; Haiman, Christopher A; Hamann, Ute; Hartman, Mikael; Miao, Hui; Hollestelle, Antoinette; Hopper, John L; Hsiung, Chia-Ni; Ito, Hidemi; Jakubowska, Anna; Johnson, Nichola; Torres, Diana; Kabisch, Maria; Kang, Daehee; Khan, Sofia; Knight, Julia A; Kosma, Veli-Matti; Lambrechts, Diether; Li, Jingmei; Lindblom, Annika; Lophatananon, Artitaya; Lubinski, Jan; Mannermaa, Arto; Manoukian, Siranoush; Le Marchand, Loic; Margolin, Sara; Marme, Frederik; Matsuo, Keitaro; McLean, Catriona; Meindl, Alfons; Muir, Kenneth; Neuhausen, Susan L; Nevanlinna, Heli; Nord, Silje; Børresen-Dale, Anne-Lise; Olson, Janet E; Orr, Nick; van den Ouweland, Ans M W; Peterlongo, Paolo; Putti, Thomas Choudary; Rudolph, Anja; Sangrajrang, Suleeporn; Sawyer, Elinor J; Schmidt, Marjanka K; Schmutzler, Rita K; Shen, Chen-Yang; Hou, Ming-Feng; Shrubsole, Matha J; Southey, Melissa C; Swerdlow, Anthony; Teo, Soo Hwang; Thienpont, Bernard; Toland, Amanda E; Tollenaar, Robert A E M; Tomlinson, Ian; Truong, Therese; Tseng, Chiu-Chen; Wen, Wanqing; Winqvist, Robert; Wu, Anna H; Yip, Cheng Har; Zamora, Pilar M; Zheng, Ying; Floris, Giuseppe; Cheng, Ching-Yu; Hooning, Maartje J; Martens, John W M; Seynaeve, Caroline; Kristensen, Vessela N; Hall, Per; Pharoah, Paul D P; Simard, Jacques; Chenevix-Trench, Georgia; Dunning, Alison M; Antoniou, Antonis C; Easton, Douglas F; Cai, Qiuyin; Long, Jirong

    2016-09-15

    Previous genome-wide association studies among women of European ancestry identified two independent breast cancer susceptibility loci represented by single nucleotide polymorphisms (SNPs) rs13281615 and rs11780156 at 8q24. A fine-mapping study across 2.06 Mb (chr8:127,561,724-129,624,067, hg19) in 55,540 breast cancer cases and 51,168 controls within the Breast Cancer Association Consortium was conducted. Three additional independent association signals in women of European ancestry, represented by rs35961416 (OR = 0.95, 95% CI = 0.93-0.97, conditional p = 5.8 × 10(-6) ), rs7815245 (OR = 0.94, 95% CI = 0.91-0.96, conditional p = 1.1 × 10(-6) ) and rs2033101 (OR = 1.05, 95% CI = 1.02-1.07, conditional p = 1.1 × 10(-4) ) were found. Integrative analysis using functional genomic data from the Roadmap Epigenomics, the Encyclopedia of DNA Elements project, the Cancer Genome Atlas and other public resources implied that SNPs rs7815245 in Signal 3, and rs1121948 in Signal 5 (in linkage disequilibrium with rs11780156, r(2)  = 0.77), were putatively functional variants for two of the five independent association signals. The results highlighted multiple 8q24 variants associated with breast cancer susceptibility in women of European ancestry. © 2016 UICC.

  9. Metaproteomics: Harnessing the power of high performance mass spectrometry to identify the suite of proteins that control metabolic activities in microbial communities

    Hettich, Robert L.; Pan, Chongle; Chourey, Karuna; Giannone, Richard J.

    2013-01-01

    Summary The availability of extensive genome information for many different microbes, including unculturable species in mixed communities from environmental samples, has enabled systems-biology interrogation by providing a means to access genomic, transcriptomic, and proteomic information. To this end, metaproteomics exploits the power of high performance mass spectrometry for extensive characterization of the complete suite of proteins expressed by a microbial community in an environmental sample. PMID:23469896

  10. Characterization of the multiple components of Acanthopanax Senticosus stem by ultra high performance liquid chromatography with quadrupole time-of-flight tandem mass spectrometry.

    Sun, Hui; Liu, Jianhua; Zhang, Aihua; Zhang, Ying; Meng, Xiangcai; Han, Ying; Zhang, Yingzhi; Wang, Xijun

    2016-02-01

    Acanthopanax Senticosus Harms. has been used widely in traditional Chinese medicine for the treatment of chronic bronchitis, neurasthenia, hypertension and ischemic heart disease. However, the in vivo constituents of the stem of Acanthopanax Senticosus remain unknown. In this paper, ultra high performance liquid chromatography with electrospray ionization quadrupole time-of-flight mass spectrometry and the MarkerLynx(TM) software combined with multiple data processing approach were used to study the constituents in vitro and in vivo. The aqueous extract from the Acanthopanax Senticosus stem and the compositions in rat serum after intragastric administration were completely analyzed. Consequently, 115 compounds in the aqueous extract from Acanthopanax Senticosus stem and 41 compounds absorbed into blood were characterized. Of the 115 compounds in vitro, 54 were reported for first time, including sinapyl alcohol, sinapyl alcohol diglucoside, and 1-O-sinapoyl-β-D-glucose. In the 41 compounds in vivo, 7 were prototype components and 34 were metabolites which were from 21 components of aqueous extract from Acanthopanax Senticosus stem, and the metabolic pathways of the metabolites were elucidated for first time. The results narrowed the range of screening the active components and provided a basis for the study of action mechanism and pharmacology. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  11. Targeted Quantitation of Site-Specific Cysteine Oxidation in Endogenous Proteins Using a Differential Alkylation and Multiple Reaction Monitoring Mass Spectrometry Approach

    Held, Jason M.; Danielson, Steven R.; Behring, Jessica B.; Atsriku, Christian; Britton, David J.; Puckett, Rachel L.; Schilling, Birgit; Campisi, Judith; Benz, Christopher C.; Gibson, Bradford W.

    2010-01-01

    Reactive oxygen species (ROS) are both physiological intermediates in cellular signaling and mediators of oxidative stress. The cysteine-specific redox-sensitivity of proteins can shed light on how ROS are regulated and function, but low sensitivity has limited quantification of the redox state of many fundamental cellular regulators in a cellular context. Here we describe a highly sensitive and reproducible oxidation analysis approach (OxMRM) that combines protein purification, differential alkylation with stable isotopes, and multiple reaction monitoring mass spectrometry that can be applied in a targeted manner to virtually any cysteine or protein. Using this approach, we quantified the site-specific cysteine oxidation status of endogenous p53 for the first time and found that Cys182 at the dimerization interface of the DNA binding domain is particularly susceptible to diamide oxidation intracellularly. OxMRM enables analysis of sulfinic and sulfonic acid oxidation levels, which we validate by assessing the oxidation of the catalytic Cys215 of protein tyrosine phosphatase-1B under numerous oxidant conditions. OxMRM also complements unbiased redox proteomics discovery studies as a verification tool through its high sensitivity, accuracy, precision, and throughput. PMID:20233844

  12. Identification of Multiple Ingredients for a Traditional Chinese Medicine Preparation (Bu-yang-huan-wu-tang by Liquid Chromatography Coupled with Tandem Mass Spectrometry

    Tung-Hu Tsai

    2013-09-01

    Full Text Available Bu-yang-huan-wu-tang (BYHWT is a popular Traditional Chinese Medicine formula consisting of seven herbal medicines (Astragalus membranaceus, Angelica sinensis, Paeonia lactiflora, Ligusticum chuanxiong, Carthamus tinctorius, Amygdalus persica and Pheretima aspergillum, that has been used in China for centuries to overcome stroke-induced disability. To ensure the consistency of quality, a reliable analytical method is required, therefore, we developed a liquid chromatography with tandem mass spectrometry (LC-MS/MS method for quantitative analysis of the major constituents in BYHWT. The herbal ingredients consisting of the cycloartane-type triterpene glycosides of astragaloside I, astragaloside II and astragaloside IV; isoflavones of formononetin, ononin calycosin, calycosin-7-O-β-d-glucoside; ligustilide and paeoniflorin were separated on a C18 column with gradient elution of methanol/10 mM ammonium acetate buffer–formic acid (100:0.1, v/v. This study was performed by a mass spectrometer using electrospray ionization (ESI with positive ionization ions monitored in the multiple reaction-monitoring (MRM mode. The linearity, accuracy, precision, limit of detection (LOD and lower limit of quantification (LLOQ were validated for this quantification method, and the sensitivity, reliability and reproducibility were all confirmed. The experiments provided a good method for analyzing BYHWT extracts. This study also quantitated the active components in various brands of commercially available products. The results indicated that the pharmaceutical industrial products of BYHWT exhibited considerable variation in their contents of the herbal compounds.

  13. Accurate Molecular Orientation Analysis Using Infrared p-Polarized Multiple-Angle Incidence Resolution Spectrometry (pMAIRS) Considering the Refractive Index of the Thin Film Sample.

    Shioya, Nobutaka; Shimoaka, Takafumi; Murdey, Richard; Hasegawa, Takeshi

    2017-06-01

    Infrared (IR) p-polarized multiple-angle incidence resolution spectrometry (pMAIRS) is a powerful tool for analyzing the molecular orientation in an organic thin film. In particular, pMAIRS works powerfully for a thin film with a highly rough surface irrespective of degree of the crystallinity. Recently, the optimal experimental condition has comprehensively been revealed, with which the accuracy of the analytical results has largely been improved. Regardless, some unresolved matters still remain. A structurally isotropic sample, for example, yields different peak intensities in the in-plane and out-of-plane spectra. In the present study, this effect is shown to be due to the refractive index of the sample film and a correction factor has been developed using rigorous theoretical methods. As a result, with the use of the correction factor, organic materials having atypical refractive indices such as perfluoroalkyl compounds ( n = 1.35) and fullerene ( n = 1.83) can be analyzed with high accuracy comparable to a compound having a normal refractive index of approximately 1.55. With this improved technique, we are also ready for discriminating an isotropic structure from an oriented sample having the magic angle of 54.7°.

  14. High-performance multiple-reflection time-of-flight mass spectrometers for research with exotic nuclei and for analytical mass spectrometry

    Plaß, Wolfgang R.; Dickel, Timo; Ayet San Andres, Samuel; Ebert, Jens; Greiner, Florian; Hornung, Christine; Jesch, Christian; Lang, Johannes; Lippert, Wayne; Majoros, Tamas; Short, Devin; Geissel, Hans; Haettner, Emma; Reiter, Moritz P.; Rink, Ann-Kathrin; Scheidenberger, Christoph; Yavor, Mikhail I.

    2015-11-01

    A class of multiple-reflection time-of-flight mass spectrometers (MR-TOF-MSs) has been developed for research with exotic nuclei at present and future accelerator facilities such as GSI and FAIR (Darmstadt), and TRIUMF (Vancouver). They can perform highly accurate mass measurements of exotic nuclei, serve as high-resolution, high-capacity mass separators and be employed as diagnostics devices to monitor the production, separation and manipulation of beams of exotic nuclei. In addition, a mobile high-resolution MR-TOF-MS has been developed for in situ applications in analytical mass spectrometry ranging from environmental research to medicine. Recently, the MR-TOF-MS for GSI and FAIR has been further developed. A novel RF quadrupole-based ion beam switchyard has been developed that allows merging and splitting of ion beams as well as transport of ions into different directions. It efficiently connects a test and reference ion source and an auxiliary detector to the system. Due to an increase in the kinetic energy of the ions in the time-of-flight analyzer of the MR-TOF-MS, a given mass resolving power is now achieved in less than half the time-of-flight. Conversely, depending on the time-of-flight, the mass resolving power has been increased by a factor of more than two.

  15. jmzReader: A Java parser library to process and visualize multiple text and XML-based mass spectrometry data formats.

    Griss, Johannes; Reisinger, Florian; Hermjakob, Henning; Vizcaíno, Juan Antonio

    2012-03-01

    We here present the jmzReader library: a collection of Java application programming interfaces (APIs) to parse the most commonly used peak list and XML-based mass spectrometry (MS) data formats: DTA, MS2, MGF, PKL, mzXML, mzData, and mzML (based on the already existing API jmzML). The library is optimized to be used in conjunction with mzIdentML, the recently released standard data format for reporting protein and peptide identifications, developed by the HUPO proteomics standards initiative (PSI). mzIdentML files do not contain spectra data but contain references to different kinds of external MS data files. As a key functionality, all parsers implement a common interface that supports the various methods used by mzIdentML to reference external spectra. Thus, when developing software for mzIdentML, programmers no longer have to support multiple MS data file formats but only this one interface. The library (which includes a viewer) is open source and, together with detailed documentation, can be downloaded from http://code.google.com/p/jmzreader/. © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  16. Identifying the Average Causal Mediation Effects with Multiple Mediators in the Presence of Treatment Non-Compliance

    Park, Soojin

    2015-01-01

    Identifying the causal mechanisms is becoming more essential in social and medical sciences. In the presence of treatment non-compliance, the Intent-To-Treated effect (hereafter, ITT effect) is identified as long as the treatment is randomized (Angrist et al., 1996). However, the mediated portion of effect is not identified without additional…

  17. Use of thermal desorption gas chromatography-olfactometry/mass spectrometry for the comparison of identified and unidentified odor active compounds emitted from building products containing linseed oil

    Clausen, P. A.; Knudsen, Henrik Nellemose; Larsen, K.

    2008-01-01

    The emission of odor active volatile organic compounds (VOCs) from a floor oil based on linseed oil, the linseed oil itself and a low-odor linseed oil was investigated by thermal desorption gas chromatography combined with olfactometry and mass spectrometry (TD-GC-O/MS). The oils were applied...... to filters and conditioned in the micro emission cell, FLEC, for 1-3 days at ambient temperature, an air exchange rate of 26.9 h-1 and a 30% relative humidity. These conditions resulted in dynamic headspace concentrations and composition of the odor active VOCs that may be similar to real indoor setting...

  18. Tandem Affinity Purification Approach Coupled to Mass Spectrometry to Identify Post-translational Modifications of Histones Associated with Chromatin-Binding Proteins.

    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.

  19. Fine-scale mapping of 8q24 locus identifies multiple independent risk variants for breast cancer

    Shi, Jiajun; Zhang, Yanfeng; Zheng, Wei

    2016-01-01

    public resources implied that SNPs rs7815245 in Signal 3, and rs1121948 in Signal 5 (in linkage disequilibrium with rs11780156, r(2)  = 0.77), were putatively functional variants for two of the five independent association signals. The results highlighted multiple 8q24 variants associated with breast...

  20. Fine-mapping identifies multiple prostate cancer risk loci at 5p15, one of which associates with TERT expression

    Kote-Jarai, Zsofia; Saunders, Edward J; Leongamornlert, Daniel A

    2013-01-01

    Associations between single nucleotide polymorphisms (SNPs) at 5p15 and multiple cancer types have been reported. We have previously shown evidence for a strong association between prostate cancer (PrCa) risk and rs2242652 at 5p15, intronic in the telomerase reverse transcriptase (TERT) gene that...

  1. Multiple response optimization for Cu, Fe and Pb determination in naphtha by graphite furnace atomic absorption spectrometry with sample injection as detergent emulsion

    Brum, Daniel M.; Lima, Claudio F.; Robaina, Nicolle F.; Fonseca, Teresa Cristina O.; Cassella, Ricardo J.

    2011-01-01

    The present paper reports the optimization for Cu, Fe and Pb determination in naphtha by graphite furnace atomic absorption spectrometry (GF AAS) employing a strategy based on the injection of the samples as detergent emulsions. The method was optimized in relation to the experimental conditions for the emulsion formation and taking into account that the three analytes (Cu, Fe and Pb) should be measured in the same emulsion. The optimization was performed in a multivariate way by employing a three-variable Doehlert design and a multiple response strategy. For this purpose, the individual responses of the three analytes were combined, yielding a global response that was employed as a dependent variable. The three factors related to the optimization process were: the concentration of HNO 3 , the concentration of the emulsifier agent (Triton X-100 or Triton X-114) in aqueous solution used to emulsify the sample and the volume of solution. At optimum conditions, it was possible to obtain satisfactory results with an emulsion formed by mixing 4 mL of the samples with 1 mL of a 4.7% w/v Triton X-100 solution prepared in 10% v/v HNO 3 medium. The resulting emulsion was stable for 250 min, at least, and provided enough sensitivity to determine the three analytes in the five samples tested. A recovery test was performed to evaluate the accuracy of the optimized procedure and recovery rates, in the range of 88-105%; 94-118% and 95-120%, were verified for Cu, Fe and Pb, respectively.

  2. Multiple response optimization for Cu, Fe and Pb determination in naphtha by graphite furnace atomic absorption spectrometry with sample injection as detergent emulsion

    Brum, Daniel M.; Lima, Claudio F. [Departamento de Quimica, Universidade Federal de Vicosa, A. Peter Henry Rolfs s/n, Vicosa/MG, 36570-000 (Brazil); Robaina, Nicolle F. [Departamento de Quimica Analitica, Universidade Federal Fluminense, Outeiro de S.J. Batista s/n, Centro, Niteroi/RJ, 24020-141 (Brazil); Fonseca, Teresa Cristina O. [Petrobras, Cenpes/PDEDS/QM, Av. Horacio Macedo 950, Ilha do Fundao, Rio de Janeiro/RJ, 21941-915 (Brazil); Cassella, Ricardo J., E-mail: cassella@vm.uff.br [Departamento de Quimica Analitica, Universidade Federal Fluminense, Outeiro de S.J. Batista s/n, Centro, Niteroi/RJ, 24020-141 (Brazil)

    2011-05-15

    The present paper reports the optimization for Cu, Fe and Pb determination in naphtha by graphite furnace atomic absorption spectrometry (GF AAS) employing a strategy based on the injection of the samples as detergent emulsions. The method was optimized in relation to the experimental conditions for the emulsion formation and taking into account that the three analytes (Cu, Fe and Pb) should be measured in the same emulsion. The optimization was performed in a multivariate way by employing a three-variable Doehlert design and a multiple response strategy. For this purpose, the individual responses of the three analytes were combined, yielding a global response that was employed as a dependent variable. The three factors related to the optimization process were: the concentration of HNO{sub 3}, the concentration of the emulsifier agent (Triton X-100 or Triton X-114) in aqueous solution used to emulsify the sample and the volume of solution. At optimum conditions, it was possible to obtain satisfactory results with an emulsion formed by mixing 4 mL of the samples with 1 mL of a 4.7% w/v Triton X-100 solution prepared in 10% v/v HNO{sub 3} medium. The resulting emulsion was stable for 250 min, at least, and provided enough sensitivity to determine the three analytes in the five samples tested. A recovery test was performed to evaluate the accuracy of the optimized procedure and recovery rates, in the range of 88-105%; 94-118% and 95-120%, were verified for Cu, Fe and Pb, respectively.

  3. Multiple viral infections in Agaricus bisporus - Characterisation of 18 unique RNA viruses and 8 ORFans identified by deep sequencing

    Deakin, Gregory; Dobbs, Edward; Bennett, Julie M.; Jones, Ian M.; Grogan, Helen M.; Burton, Kerry S.

    2017-01-01

    Thirty unique non-host RNAs were sequenced in the cultivated fungus, Agaricus bisporus, comprising 18 viruses each encoding an RdRp domain with an additional 8 ORFans (non-host RNAs with no similarity to known sequences). Two viruses were multipartite with component RNAs showing correlative abundances and common 3′ motifs. The viruses, all positive sense single-stranded, were classified into diverse orders/families. Multiple infections of Agaricus may represent a diverse, dynamic and interact...

  4. Speciation analysis of arsenic in biological matrices by automated hydride generation-cryotrapping-atomic absorption spectrometry with multiple microflame quartz tube atomizer (multiatomizer).

    This paper describes an automated system for the oxidation state specific speciation of inorganic and methylated arsenicals by selective hydride generation - cryotrapping- gas chromatography - atomic absorption spectrometry with the multiatomizer. The corresponding arsines are ge...

  5. EPA CRL MS014: Analysis of Aldicarb, Bromadiolone, Carbofuran, Oxamyl and Methomyl in Water by Multiple Reaction Monitoring Liquid Chromatography / Tandem Mass Spectrometry (LC/MS/MS)

    Method MS014 describes procedures for solvent extraction of aldicarb, bromadiolone, carbofuran, oxamyl and methomyl from water samples, followed by analysis using liquid chromatography tandem mass spectrometry (LC-MS-MS).

  6. Principal component analysis of normalized full spectrum mass spectrometry data in multiMS-toolbox: An effective tool to identify important factors for classification of different metabolic patterns and bacterial strains.

    Cejnar, Pavel; Kuckova, Stepanka; Prochazka, Ales; Karamonova, Ludmila; Svobodova, Barbora

    2018-06-15

    Explorative statistical analysis of mass spectrometry data is still a time-consuming step. We analyzed critical factors for application of principal component analysis (PCA) in mass spectrometry and focused on two whole spectrum based normalization techniques and their application in the analysis of registered peak data and, in comparison, in full spectrum data analysis. We used this technique to identify different metabolic patterns in the bacterial culture of Cronobacter sakazakii, an important foodborne pathogen. Two software utilities, the ms-alone, a python-based utility for mass spectrometry data preprocessing and peak extraction, and the multiMS-toolbox, an R software tool for advanced peak registration and detailed explorative statistical analysis, were implemented. The bacterial culture of Cronobacter sakazakii was cultivated on Enterobacter sakazakii Isolation Agar, Blood Agar Base and Tryptone Soya Agar for 24 h and 48 h and applied by the smear method on an Autoflex speed MALDI-TOF mass spectrometer. For three tested cultivation media only two different metabolic patterns of Cronobacter sakazakii were identified using PCA applied on data normalized by two different normalization techniques. Results from matched peak data and subsequent detailed full spectrum analysis identified only two different metabolic patterns - a cultivation on Enterobacter sakazakii Isolation Agar showed significant differences to the cultivation on the other two tested media. The metabolic patterns for all tested cultivation media also proved the dependence on cultivation time. Both whole spectrum based normalization techniques together with the full spectrum PCA allow identification of important discriminative factors in experiments with several variable condition factors avoiding any problems with improper identification of peaks or emphasis on bellow threshold peak data. The amounts of processed data remain still manageable. Both implemented software utilities are available

  7. MUSI: an integrated system for identifying multiple specificity from very large peptide or nucleic acid data sets.

    Kim, Taehyung; Tyndel, Marc S; Huang, Haiming; Sidhu, Sachdev S; Bader, Gary D; Gfeller, David; Kim, Philip M

    2012-03-01

    Peptide recognition domains and transcription factors play crucial roles in cellular signaling. They bind linear stretches of amino acids or nucleotides, respectively, with high specificity. Experimental techniques that assess the binding specificity of these domains, such as microarrays or phage display, can retrieve thousands of distinct ligands, providing detailed insight into binding specificity. In particular, the advent of next-generation sequencing has recently increased the throughput of such methods by several orders of magnitude. These advances have helped reveal the presence of distinct binding specificity classes that co-exist within a set of ligands interacting with the same target. Here, we introduce a software system called MUSI that can rapidly analyze very large data sets of binding sequences to determine the relevant binding specificity patterns. Our pipeline provides two major advances. First, it can detect previously unrecognized multiple specificity patterns in any data set. Second, it offers integrated processing of very large data sets from next-generation sequencing machines. The results are visualized as multiple sequence logos describing the different binding preferences of the protein under investigation. We demonstrate the performance of MUSI by analyzing recent phage display data for human SH3 domains as well as microarray data for mouse transcription factors.

  8. Integration of paper-based microarray and time-of-flight secondary ion mass spectrometry (ToF-SIMS) for parallel detection and quantification of molecules in multiple samples automatically.

    Chu, Kuo-Jui; Chen, Po-Chun; You, Yun-Wen; Chang, Hsun-Yun; Kao, Wei-Lun; Chu, Yi-Hsuan; Wu, Chen-Yi; Shyue, Jing-Jong

    2018-04-16

    With its low-cost fabrication and ease of modification, paper-based analytical devices have developed rapidly in recent years. Microarrays allow automatic analysis of multiple samples or multiple reactions with minimal sample consumption. While cellulose paper is generally used, its high backgrounds in spectrometry outside of the visible range has limited its application to be mostly colorimetric analysis. In this work, glass-microfiber paper is used as the substrate for a microarray. The glass-microfiber is essentially chemically inert SiO x , and the lower background from this inorganic microfiber can avoid interference from organic analytes in various spectrometers. However, generally used wax printing fails to wet glass microfibers to form hydrophobic barriers. Therefore, to prepare the hydrophobic-hydrophilic pattern, the glass-microfiber paper was first modified with an octadecyltrichlorosilane (OTS) self-assembled monolayer (SAM) to make the paper hydrophobic. A hydrophilic microarray was then prepared using a CO 2 laser scriber that selectively removed the OTS layer with a designed pattern. One microliter of aqueous drops of peptides at various concentrations were then dispensed inside the round patterns where OTS SAM was removed while the surrounding area with OTS layer served as a barrier to separate each drop. The resulting specimen of multiple spots was automatically analyzed with a time-of-flight secondary ion mass spectrometer (ToF-SIMS), and all of the secondary ions were collected. Among the various cluster ions that have developed over the past decade, pulsed C 60 + was selected as the primary ion because of its high secondary ion intensity in the high mass region, its minimal alteration of the surface when operating within the static-limit and spatial resolution at the ∼μm level. In the resulting spectra, parent ions of various peptides (in the forms [M+H] + and [M+Na] + ) were readily identified for parallel detection of molecules in a mixture

  9. Meta-analysis of five genome-wide association studies identifies multiple new loci associated with testicular germ cell tumor

    Wang, Zhaoming; McGlynn, Katherine A.; Rajpert-De Meyts, Ewa

    2017-01-01

    The international Testicular Cancer Consortium (TECAC) combined five published genome-wide association studies of testicular germ cell tumor (TGCT; 3,558 cases and 13,970 controls) to identify new susceptibility loci. We conducted a fixed-effects meta-analysis, including, to our knowledge, the fi...

  10. Fine-scale mapping of 8q24 locus identifies multiple independent risk variants for breast cancer

    J. Shi (Jiajun); Zhang, Y. (Yanfeng); W. Zheng (Wei); K. Michailidou (Kyriaki); M. Ghoussaini (Maya); M.K. Bolla (Manjeet K.); Wang, Q. (Qin); J. Dennis (Joe); Lush, M. (Michael); R.L. Milne (Roger); X.-O. Shu (Xiao-Ou); J. Beesley (Jonathan); S. Kar (Siddhartha); I.L. Andrulis (Irene); H. Anton-Culver (Hoda); Arndt, V. (Volker); M.W. Beckmann (Matthias); Z. Zhao (Zhiguo); Guo, X. (Xingyi); J. Benítez (Javier); A. Beeghly-Fadiel (Alicia); W.J. Blot (William); N.V. Bogdanova (Natalia); S.E. Bojesen (Stig); H. Brauch (Hiltrud); H. Brenner (Hermann); L.A. Brinton (Louise); A. Broeks (Annegien); T. Brüning (Thomas); B. Burwinkel (Barbara); H. Cai (Hui); S. Canisius (Sander); J. Chang-Claude (Jenny); Choi, J.-Y. (Ji-Yeob); F.J. Couch (Fergus); A. Cox (Angela); S.S. Cross (Simon); K. Czene (Kamila); H. Darabi (Hatef); P. Devilee (Peter); A. Droit (Arnaud); T. Dörk (Thilo); P.A. Fasching (Peter); O. Fletcher (Olivia); H. Flyger (Henrik); F. Fostira (Florentia); Gaborieau, V. (Valerie); M. García-Closas (Montserrat); G.G. Giles (Graham); Grip, M. (Mervi); P. Guénel (Pascal); C.A. Haiman (Christopher A.); U. Hamann (Ute); J.M. Hartman (Joost); X. Miao; A. Hollestelle (Antoinette); J.L. Hopper (John); Hsiung, C.-N. (Chia-Ni); H. Ito (Hidemi); A. Jakubowska (Anna); Johnson, N. (Nichola); D. Torres (Diana); M. Kabisch (Maria); D. Kang (Daehee); S. Khan (Sofia); J.A. Knight (Julia); V-M. Kosma (Veli-Matti); Lambrechts, D. (Diether); J. Li (Jingmei); A. Lindblom (Annika); A. Lophatananon (Artitaya); J. Lubinski (Jan); A. Mannermaa (Arto); S. Manoukian (Siranoush); L. Le Marchand (Loic); S. Margolin (Sara); Marme, F. (Frederik); K. Matsuo (Keitaro); C.A. McLean (Catriona Ann); A. Meindl (Alfons); K.R. Muir (K.); S.L. Neuhausen (Susan); H. Nevanlinna (Heli); S. Nord (Silje); A.-L. Borresen-Dale (Anne-Lise); J.E. Olson (Janet); N. Orr (Nick); A.M.W. van den Ouweland (Ans); P. Peterlongo (Paolo); T.C. Putti (Thomas Choudary); Rudolph, A. (Anja); Sangrajrang, S. (Suleeporn); E.J. Sawyer (Elinor); M.K. Schmidt (Marjanka); R.K. Schmutzler (Rita); C.-Y. Shen (Chen-Yang); M.-F. Hou (Ming-Feng); M. Shrubsole (Martha); M.C. Southey (Melissa); A.J. Swerdlow (Anthony ); Hwang Teo, S. (Soo); B. Thienpont (Bernard); A.E. Toland (Amanda); R.A.E.M. Tollenaar (Rob); I.P. Tomlinson (Ian); T. Truong (Thérèse); C.-C. Tseng (Chiu-Chen); W. Wen (Wanqing); R. Winqvist (Robert); A.H. Wu (Anna); C. Har Yip (Cheng); P.M. Zamora (Pilar M.); Zheng, Y. (Ying); O.A.M. Floris; Cheng, C.-Y. (Ching-Yu); M.J. Hooning (Maartje); J.W.M. Martens (John); C.M. Seynaeve (Caroline); V. Kristensen (Vessela); P. Hall (Per); P.D.P. Pharoah (Paul); J. Simard (Jacques); G. Chenevix-Trench (Georgia); A.M. Dunning (Alison); A.C. Antoniou (Antonis C.); D.F. Easton (Douglas F.); Q. Cai (Qiuyin); J. Long (Jirong)

    2016-01-01

    textabstractPrevious genome-wide association studies among women of European ancestry identified two independent breast cancer susceptibility loci represented by single nucleotide polymorphisms (SNPs) rs13281615 and rs11780156 at 8q24. A fine-mapping study across 2.06 Mb

  11. A meta-analysis identifies adolescent idiopathic scoliosis association with LBX1 locus in multiple ethnic groups

    Londono, Douglas; Kou, Ikuyo; Johnson, Todd A

    2014-01-01

    BACKGROUND: Adolescent idiopathic scoliosis (AIS) is a common rotational deformity of the spine that presents in children worldwide, yet its etiology is poorly understood. Recent genome-wide association studies (GWAS) have identified a few candidate risk loci. One locus near the chromosome 10q24....

  12. A Comparison of Multiple Facets of Self-Concept in Gifted vs. Non-Identified Israeli Students

    Zeidner, Moshe; Shani-Zinovich, Inbal

    2015-01-01

    This study compares facets of self-concept in gifted and non-identified Israeli adolescent students. The self-concept mean score profile of gifted vs. non-selected Israeli students was significantly different, with gifted students reporting higher mean levels of academic self-concept, but lower mean levels of social, personal, and physical…

  13. Quadrupole time-of-flight mass spectrometry: a method to study the actual expression of allergen isoforms identified by PCR cloning

    Helsper, Johannes P. F. G.; Gilissen, Luud J. W. J.; van Ree, Ronald; America, Antoine H. P.; Cordewener, Jan H. G.; Bosch, Dirk

    2002-01-01

    BACKGROUND: Over the past 2 decades, molecular biology has shown that most major allergens exist in multiple isoforms. Very little is known about the relevance of allergen isoforms at the level of expressed protein (ie, actual allergen exposure). OBJECTIVE: The aim of this study was to evaluate the

  14. Cellular Proliferation by Multiplex Immunohistochemistry Identifies High-Risk Multiple Myeloma in Newly Diagnosed, Treatment-Naive Patients.

    Ely, Scott; Forsberg, Peter; Ouansafi, Ihsane; Rossi, Adriana; Modin, Alvin; Pearse, Roger; Pekle, Karen; Perry, Arthur; Coleman, Morton; Jayabalan, David; Di Liberto, Maurizio; Chen-Kiang, Selina; Niesvizky, Ruben; Mark, Tomer M

    2017-12-01

    Therapeutic options for multiple myeloma (MM) are growing, yet clinical outcomes remain heterogeneous. Cytogenetic analysis and disease staging are mainstays of risk stratification, but data suggest a complex interplay between numerous abnormalities. Myeloma cell proliferation is a metric shown to predict outcomes, but available methods are not feasible in clinical practice. Multiplex immunohistochemistry (mIHC), using multiple immunostains simultaneously, is universally available for clinical use. We tested mIHC as a method to calculate a plasma cell proliferation index (PCPI). By mIHC, marrow trephine core biopsy samples were costained for CD138, a plasma cell-specific marker, and Ki-67. Myeloma cells (CD138 + ) were counted as proliferating if coexpressing Ki-67. Retrospective analysis was performed on 151 newly diagnosed, treatment-naive patients divided into 2 groups on the basis of myeloma cell proliferation: low (PCPI ≤ 5%, n = 87), and high (PCPI > 5%, n = 64). Median overall survival (OS) was not reached versus 78.9 months (P = .0434) for the low versus high PCPI groups. Multivariate analysis showed that only high-risk cytogenetics (hazard ratio [HR] = 2.02; P = .023), International Staging System (ISS) stage > I (HR = 2.30; P = .014), and PCPI > 5% (HR = 1.70; P = .041) had independent effects on OS. Twenty-three (36%) of the 64 patients with low-risk disease (ISS stage 1, without high-risk cytogenetics) were uniquely reidentified as high risk by PCPI. PCPI is a practical method that predicts OS in newly diagnosed myeloma and facilitates broader use of MM cell proliferation for risk stratification. Copyright © 2017 Elsevier Inc. All rights reserved.

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

    Jia Yan

    2012-07-01

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

  16. Integrated microarray and ChIP analysis identifies multiple Foxa2 dependent target genes in the notochord.

    Tamplin, Owen J; Cox, Brian J; Rossant, Janet

    2011-12-15

    The node and notochord are key tissues required for patterning of the vertebrate body plan. Understanding the gene regulatory network that drives their formation and function is therefore important. Foxa2 is a key transcription factor at the top of this genetic hierarchy and finding its targets will help us to better understand node and notochord development. We performed an extensive microarray-based gene expression screen using sorted embryonic notochord cells to identify early notochord-enriched genes. We validated their specificity to the node and notochord by whole mount in situ hybridization. This provides the largest available resource of notochord-expressed genes, and therefore candidate Foxa2 target genes in the notochord. Using existing Foxa2 ChIP-seq data from adult liver, we were able to identify a set of genes expressed in the notochord that had associated regions of Foxa2-bound chromatin. Given that Foxa2 is a pioneer transcription factor, we reasoned that these sites might represent notochord-specific enhancers. Candidate Foxa2-bound regions were tested for notochord specific enhancer function in a zebrafish reporter assay and 7 novel notochord enhancers were identified. Importantly, sequence conservation or predictive models could not have readily identified these regions. Mutation of putative Foxa2 binding elements in two of these novel enhancers abrogated reporter expression and confirmed their Foxa2 dependence. The combination of highly specific gene expression profiling and genome-wide ChIP analysis is a powerful means of understanding developmental pathways, even for small cell populations such as the notochord. Copyright © 2011 Elsevier Inc. All rights reserved.

  17. Accurately Identifying New QoS Violation Driven by High-Distributed Low-Rate Denial of Service Attacks Based on Multiple Observed Features

    Jian Kang

    2015-01-01

    Full Text Available We propose using multiple observed features of network traffic to identify new high-distributed low-rate quality of services (QoS violation so that detection accuracy may be further improved. For the multiple observed features, we choose F feature in TCP packet header as a microscopic feature and, P feature and D feature of network traffic as macroscopic features. Based on these features, we establish multistream fused hidden Markov model (MF-HMM to detect stealthy low-rate denial of service (LDoS attacks hidden in legitimate network background traffic. In addition, the threshold value is dynamically adjusted by using Kaufman algorithm. Our experiments show that the additive effect of combining multiple features effectively reduces the false-positive rate. The average detection rate of MF-HMM results in a significant 23.39% and 44.64% improvement over typical power spectrum density (PSD algorithm and nonparametric cumulative sum (CUSUM algorithm.

  18. Use of diffusion tensor imaging to identify similarities and differences between cerebellar and Parkinsonism forms of multiple system atrophy

    Wang, Po-Shan; Wu, Hsiu-Mei; Lin, Ching-Po; Soong, Bing-Wen

    2011-01-01

    We performed diffusion tensor imaging to determine if multiple system atrophy (MSA)-cerebellar (C) and MSA-Parkinsonism (P) show similar changes, as shown in pathological studies. Nineteen patients with MSA-C, 12 patients with MSA-P, 20 patients with Parkinson disease, and 20 healthy controls were evaluated with the use of voxel-based morphometry analysis of diffusion tensor imaging. There was an increase in apparent diffusion coefficient values in the middle cerebellar peduncles and cerebellum and a decrease in fractional anisotropy in the pyramidal tract, middle cerebellar peduncles, and white matter of the cerebellum in patients with MSA-C and MSA-P compared to the controls (P<0.001). In addition, isotropic diffusion-weighted image values were reduced in the cerebellar cortex and deep cerebellar nuclei in patients with MSA-C and increased in the basal ganglia in patients with MSA-P. These results indicate that despite their disparate clinical manifestations, patients with MSA-C and MSA-P share similar diffusion tensor imaging features in the infratentorial region. Further, the combination of FA, ADC and iDWI images can be used to distinguish between MSA (either form) and Parkinson disease, which has potential therapeutic implications. (orig.)

  19. Use of diffusion tensor imaging to identify similarities and differences between cerebellar and Parkinsonism forms of multiple system atrophy

    Wang, Po-Shan [National Yang-Ming University, Department of Neurology, School of Medicine, Taipei (China); Taipei Veterans General Hospital, Neurological Institute, Taipei (China); Taipei Municipal Gan-Dau Hospital, Neurological Institute, Taipei (China); National Yang-Ming University, Institute of Brain Science, Taipei (China); Wu, Hsiu-Mei [National Yang-Ming University, Department of Neurology, School of Medicine, Taipei (China); Taipei Veterans General Hospital, Department of Radiology, Taipei (China); Lin, Ching-Po [National Yang-Ming University, Institute of Brain Science, Taipei (China); Soong, Bing-Wen [National Yang-Ming University, Department of Neurology, School of Medicine, Taipei (China); Taipei Veterans General Hospital, Neurological Institute, Taipei (China)

    2011-07-15

    We performed diffusion tensor imaging to determine if multiple system atrophy (MSA)-cerebellar (C) and MSA-Parkinsonism (P) show similar changes, as shown in pathological studies. Nineteen patients with MSA-C, 12 patients with MSA-P, 20 patients with Parkinson disease, and 20 healthy controls were evaluated with the use of voxel-based morphometry analysis of diffusion tensor imaging. There was an increase in apparent diffusion coefficient values in the middle cerebellar peduncles and cerebellum and a decrease in fractional anisotropy in the pyramidal tract, middle cerebellar peduncles, and white matter of the cerebellum in patients with MSA-C and MSA-P compared to the controls (P<0.001). In addition, isotropic diffusion-weighted image values were reduced in the cerebellar cortex and deep cerebellar nuclei in patients with MSA-C and increased in the basal ganglia in patients with MSA-P. These results indicate that despite their disparate clinical manifestations, patients with MSA-C and MSA-P share similar diffusion tensor imaging features in the infratentorial region. Further, the combination of FA, ADC and iDWI images can be used to distinguish between MSA (either form) and Parkinson disease, which has potential therapeutic implications. (orig.)

  20. Use of diffusion tensor imaging to identify similarities and differences between cerebellar and Parkinsonism forms of multiple system atrophy.

    Wang, Po-Shan; Wu, Hsiu-Mei; Lin, Ching-Po; Soong, Bing-Wen

    2011-07-01

    We performed diffusion tensor imaging to determine if multiple system atrophy (MSA)-cerebellar (C) and MSA-Parkinsonism (P) show similar changes, as shown in pathological studies. Nineteen patients with MSA-C, 12 patients with MSA-P, 20 patients with Parkinson disease, and 20 healthy controls were evaluated with the use of voxel-based morphometry analysis of diffusion tensor imaging. There was an increase in apparent diffusion coefficient values in the middle cerebellar peduncles and cerebellum and a decrease in fractional anisotropy in the pyramidal tract, middle cerebellar peduncles, and white matter of the cerebellum in patients with MSA-C and MSA-P compared to the controls (P < 0.001). In addition, isotropic diffusion-weighted image values were reduced in the cerebellar cortex and deep cerebellar nuclei in patients with MSA-C and increased in the basal ganglia in patients with MSA-P. These results indicate that despite their disparate clinical manifestations, patients with MSA-C and MSA-P share similar diffusion tensor imaging features in the infratentorial region. Further, the combination of FA, ADC and iDWI images can be used to distinguish between MSA (either form) and Parkinson disease, which has potential therapeutic implications.

  1. Is it possible to rapidly and noninvasively identify different plants from Asteraceae using electronic nose with multiple mathematical algorithms?

    Hui-Qin Zou

    2015-12-01

    Full Text Available Many plants originating from the Asteraceae family are applied as herbal medicines and also beverage ingredients in Asian areas, particularly in China. However, they may be confused due to their similar odor, especially when ground into powder, losing their typical macroscopic characteristics. In this paper, 11 different multiple mathematical algorithms, which are commonly used in data processing, were utilized and compared to analyze the electronic nose (E-nose response signals of different plants from Asteraceae family. Results demonstrate that three-dimensional plot scatter figure of principal component analysis with less extracted components could offer the identification results more visually; simultaneously, all nine kinds of artificial neural network could give classification accuracies at 100%. This paper presents a rapid, accurate, and effective method to distinguish Asteraceae plants based on their response signals in E-nose. It also gives insights to further studies, such as to find unique sensors that are more sensitive and exclusive to volatile components in Chinese herbal medicines and to improve the identification ability of E-nose. Screening sensors made by other novel materials would be also an interesting way to improve identification capability of E-nose.

  2. Multiple novel prostate cancer susceptibility signals identified by fine-mapping of known risk loci among Europeans

    Amin Al Olama, Ali; Dadaev, Tokhir; Hazelett, Dennis J

    2015-01-01

    associated lead SNP, while the originally reported variant remained as the lead SNP only in 4 regions. We also confirmed two association signals in Europeans that had been previously reported only in East-Asian GWAS. Based on statistical evidence and linkage disequilibrium (LD) structure, we have curated...... identified here alongside the refined data for existing association signals, we estimate that these loci now explain ∼38.9% of the familial relative risk of PrCa, an 8.9% improvement over the previously reported GWAS tag SNPs. This suggests that a significant fraction of the heritability of PrCa may have...

  3. A common rejection module (CRM) for acute rejection across multiple organs identifies novel therapeutics for organ transplantation.

    Khatri, Purvesh; Roedder, Silke; Kimura, Naoyuki; De Vusser, Katrien; Morgan, Alexander A; Gong, Yongquan; Fischbein, Michael P; Robbins, Robert C; Naesens, Maarten; Butte, Atul J; Sarwal, Minnie M

    2013-10-21

    Using meta-analysis of eight independent transplant datasets (236 graft biopsy samples) from four organs, we identified a common rejection module (CRM) consisting of 11 genes that were significantly overexpressed in acute rejection (AR) across all transplanted organs. The CRM genes could diagnose AR with high specificity and sensitivity in three additional independent cohorts (794 samples). In another two independent cohorts (151 renal transplant biopsies), the CRM genes correlated with the extent of graft injury and predicted future injury to a graft using protocol biopsies. Inferred drug mechanisms from the literature suggested that two FDA-approved drugs (atorvastatin and dasatinib), approved for nontransplant indications, could regulate specific CRM genes and reduce the number of graft-infiltrating cells during AR. We treated mice with HLA-mismatched mouse cardiac transplant with atorvastatin and dasatinib and showed reduction of the CRM genes, significant reduction of graft-infiltrating cells, and extended graft survival. We further validated the beneficial effect of atorvastatin on graft survival by retrospective analysis of electronic medical records of a single-center cohort of 2,515 renal transplant patients followed for up to 22 yr. In conclusion, we identified a CRM in transplantation that provides new opportunities for diagnosis, drug repositioning, and rational drug design.

  4. Multiple choice questions are superior to extended matching questions to identify medicine and biomedical sciences students who perform poorly.

    Eijsvogels, Thijs M H; van den Brand, Tessa L; Hopman, Maria T E

    2013-11-01

    In recent years, medical faculties at Dutch universities have implemented a legally binding study advice to students of medicine and biomedical sciences during their propaedeutic phase. Appropriate examination is essential to discriminate between poor (grade age and examination preference on this score. Data were collected for 452 first-year medical and biomedical science students during three distinct course examinations: one examination with EMQ only, one with MCQ only and one mixed examination (including EMQ and MCQ). Logistic regression analysis revealed that MCQ examination was 3 times better in identifying poor students compared with EMQ (RR 3.0, CI 2.0-4.5), whereas EMQ better detected excellent students (average grade ≥8) (RR 1.93, CI 1.47-2.53). Mixed examination had comparable characteristics to MCQ. Sex and examination preference did not impact the score of the student. Students ≥20 years had a 4-fold higher risk ratio of obtaining a poor grade (<6) compared with students ≤18 years old (RR 4.1, CI 2.1-8.0). Given the strong discriminative capacity of MCQ examinations to identify poor students, we recommend the use of this type of examination during the propaedeutic phase of medicine and biomedical science study programmes, in the light of the binding study advice.

  5. Genome-wide association study identifies multiple loci associated with both mammographic density and breast cancer risk

    Lindström, Sara; Thompson, Deborah J.; Paterson, Andrew D.; Li, Jingmei; Gierach, Gretchen L.; Scott, Christopher; Stone, Jennifer; Douglas, Julie A.; dos-Santos-Silva, Isabel; Fernandez-Navarro, Pablo; Verghase, Jajini; Smith, Paula; Brown, Judith; Luben, Robert; Wareham, Nicholas J.; Loos, Ruth J.F.; Heit, John A.; Pankratz, V. Shane; Norman, Aaron; Goode, Ellen L.; Cunningham, Julie M.; deAndrade, Mariza; Vierkant, Robert A.; Czene, Kamila; Fasching, Peter A.; Baglietto, Laura; Southey, Melissa C.; Giles, Graham G.; Shah, Kaanan P.; Chan, Heang-Ping; Helvie, Mark A.; Beck, Andrew H.; Knoblauch, Nicholas W.; Hazra, Aditi; Hunter, David J.; Kraft, Peter; Pollan, Marina; Figueroa, Jonine D.; Couch, Fergus J.; Hopper, John L.; Hall, Per; Easton, Douglas F.; Boyd, Norman F.; Vachon, Celine M.; Tamimi, Rulla M.

    2015-01-01

    Mammographic density reflects the amount of stromal and epithelial tissues in relation to adipose tissue in the breast and is a strong risk factor for breast cancer. Here we report the results from meta-analysis of genome-wide association studies (GWAS) of three mammographic density phenotypes: dense area, non-dense area and percent density in up to 7,916 women in stage 1 and an additional 10,379 women in stage 2. We identify genome-wide significant (P<5×10−8) loci for dense area (AREG, ESR1, ZNF365, LSP1/TNNT3, IGF1, TMEM184B, SGSM3/MKL1), non-dense area (8p11.23) and percent density (PRDM6, 8p11.23, TMEM184B). Four of these regions are known breast cancer susceptibility loci, and four additional regions were found to be associated with breast cancer (P<0.05) in a large meta-analysis. These results provide further evidence of a shared genetic basis between mammographic density and breast cancer and illustrate the power of studying intermediate quantitative phenotypes to identify putative disease susceptibility loci. PMID:25342443

  6. Item and test analysis to identify quality multiple choice questions (MCQS from an assessment of medical students of Ahmedabad, Gujarat

    Sanju Gajjar

    2014-01-01

    Full Text Available Background: Multiple choice questions (MCQs are frequently used to assess students in different educational streams for their objectivity and wide reach of coverage in less time. However, the MCQs to be used must be of quality which depends upon its difficulty index (DIF I, discrimination index (DI and distracter efficiency (DE. Objective: To evaluate MCQs or items and develop a pool of valid items by assessing with DIF I, DI and DE and also to revise/ store or discard items based on obtained results. Settings: Study was conducted in a medical school of Ahmedabad. Materials and Methods: An internal examination in Community Medicine was conducted after 40 hours teaching during 1 st MBBS which was attended by 148 out of 150 students. Total 50 MCQs or items and 150 distractors were analyzed. Statistical Analysis: Data was entered and analyzed in MS Excel 2007 and simple proportions, mean, standard deviations, coefficient of variation were calculated and unpaired t test was applied. Results: Out of 50 items, 24 had "good to excellent" DIF I (31 - 60% and 15 had "good to excellent" DI (> 0.25. Mean DE was 88.6% considered as ideal/ acceptable and non functional distractors (NFD were only 11.4%. Mean DI was 0.14. Poor DI (< 0.15 with negative DI in 10 items indicates poor preparedness of students and some issues with framing of at least some of the MCQs. Increased proportion of NFDs (incorrect alternatives selected by < 5% students in an item decrease DE and makes it easier. There were 15 items with 17 NFDs, while rest items did not have any NFD with mean DE of 100%. Conclusion: Study emphasizes the selection of quality MCQs which truly assess the knowledge and are able to differentiate the students of different abilities in correct manner.

  7. Identifying conditions for inducible protein production in E. coli: combining a fed-batch and multiple induction approach

    Choi Young J

    2006-08-01

    Full Text Available Abstract Background In the interest of generating large amounts of recombinant protein, inducible systems have been studied to maximize both the growth of the culture and the production of foreign proteins. Even though thermo-inducible systems were developed in the late 1970's, the number of studies that focus on strategies for the implementation at bioreactor scale is limited. In this work, the bacteriophage lambda PL promoter is once again investigated as an inducible element but for the production of green fluorescent protein (GFP. Culture temperature, induction point, induction duration and number of inductions were considered as factors to maximize GFP production in a 20-L bioreactor. Results It was found that cultures carried out at 37°C resulted in a growth-associated production of GFP without the need of an induction at 42°C. Specific production was similar to what was achieved when separating the growth and production phases. Shake flask cultures were used to screen for desirable operating conditions. It was found that multiple inductions increased the production of GFP. Induction decreased the growth rate and substrate yield coefficients; therefore, two time domains (before and after induction having different kinetic parameters were created to fit a model to the data collected. Conclusion Based on two batch runs and the simulation of culture dynamics, a pre-defined feeding and induction strategy was developed to increase the volumetric yield of a temperature regulated expression system and was successfully implemented in a 20-L bioreactor. An overall cell density of 5.95 g DW l-1 was achieved without detriment to the cell specific production of GFP; however, the production of GFP was underestimated in the simulations due to a significant contribution of non-growth associated product formation under limiting nutrient conditions.

  8. Investigation of Pseudomonas aeruginosa quorum-sensing signaling system for identifying multiple inhibitors using molecular docking and structural analysis methodology.

    Soheili, Vahid; Bazzaz, Bibi Sedigheh Fazly; Abdollahpour, Nooshin; Hadizadeh, Farzin

    2015-12-01

    Pseudomonas aeruginosa is an opportunistic human pathogen and a common Gram-negative bacterium in hospital-acquired infections. It causes death in many burn victims, cystic-fibrosis and neutropenic-cancer patients. It is known that P. aeruginosa biofilm maturation and production of cell-associated and extracellular virulence factors such as pyocyanin, elastase and rhamnolipids are under the control of a quorum-sensing (QS) system. Among several proteins involved in the Pseudomonas QS mechanism, LasR and PqsE play an important role in its cascade signaling system. They can cause increases in QS factors, biofilm maturation, and the production of virulence factors. Therefore, inhibition of these proteins can reduce the pathogenicity of P. aeruginosa. According to the structure of corresponding auto-inducers bound to these proteins, in silico calculations were performed with some non-steroidal anti-inflammatory drugs (NSAIDs) to estimate possible interactions and find the co-inhibitors of LasR and PqsE. The results showed that oxicams (Piroxicam and Meloxicam) can interact well with active sites of both proteins with the Ki of 119.43 nM and 4.0 μM for Meloxicam and 201.39 nM and 4.88 μM against LasR and PqsE, respectively. These findings suggested that Piroxicam and Meloxicam can be used as potential inhibitors for control of the P. aeruginosa QS signaling system and biofilm formation, and may be used in the design of multiple inhibitors. Copyright © 2015 Elsevier Ltd. All rights reserved.

  9. Identifying multiple timescale rainfall controls on Mojave Desert ecohydrology using an integrated data and modeling approach for Larrea tridentata

    Ng, Gene-Hua Crystal; Bedford, David R.; Miller, David M.

    2015-01-01

    The perennial shrub Larrea tridentata is widely successful in North American warm deserts but is also susceptible to climatic perturbations. Understanding its response to rainfall variability requires consideration of multiple timescales. We examine intra-annual to multi-year relationships using model simulations of soil moisture and vegetation growth over 50 years in the Mojave National Preserve in southeastern California (USA). Ecohydrological model parameters are conditioned on field and remote sensing data using an ensemble Kalman filter. Although no specific periodicities were detected in the rainfall record, simulated leaf-area-index exhibits multi-year dynamics that are driven by multi-year (∼3-years) rains, but with up to a 1-year delay in peak response. Within a multi-year period, Larrea tridentata is more sensitive to winter rains than summer. In the most active part of the root zone (above ∼80 cm), >1-year average soil moisture drives vegetation growth, but monthly average soil moisture is controlled by root uptake. Moisture inputs reach the lower part of the root zone (below ∼80 cm) infrequently, but once there they can persist over a year to help sustain plant growth. Parameter estimates highlight efficient plant physiological properties facilitating persistent growth and high soil hydraulic conductivity allowing deep soil moisture stores. We show that soil moisture as an ecological indicator is complicated by bidirectional interactions with vegetation that depend on timescale and depth. Under changing climate, Larrea tridentata will likely be relatively resilient to shorter-term moisture variability but will exhibit higher sensitivity to shifts in seasonal to multi-year moisture inputs.

  10. Using empirical models of species colonization under multiple threatening processes to identify complementary threat-mitigation strategies.

    Tulloch, Ayesha I T; Mortelliti, Alessio; Kay, Geoffrey M; Florance, Daniel; Lindenmayer, David

    2016-08-01

    Approaches to prioritize conservation actions are gaining popularity. However, limited empirical evidence exists on which species might benefit most from threat mitigation and on what combination of threats, if mitigated simultaneously, would result in the best outcomes for biodiversity. We devised a way to prioritize threat mitigation at a regional scale with empirical evidence based on predicted changes to population dynamics-information that is lacking in most threat-management prioritization frameworks that rely on expert elicitation. We used dynamic occupancy models to investigate the effects of multiple threats (tree cover, grazing, and presence of an hyperaggressive competitor, the Noisy Miner (Manorina melanocephala) on bird-population dynamics in an endangered woodland community in southeastern Australia. The 3 threatening processes had different effects on different species. We used predicted patch-colonization probabilities to estimate the benefit to each species of removing one or more threats. We then determined the complementary set of threat-mitigation strategies that maximized colonization of all species while ensuring that redundant actions with little benefit were avoided. The single action that resulted in the highest colonization was increasing tree cover, which increased patch colonization by 5% and 11% on average across all species and for declining species, respectively. Combining Noisy Miner control with increasing tree cover increased species colonization by 10% and 19% on average for all species and for declining species respectively, and was a higher priority than changing grazing regimes. Guidance for prioritizing threat mitigation is critical in the face of cumulative threatening processes. By incorporating population dynamics in prioritization of threat management, our approach helps ensure funding is not wasted on ineffective management programs that target the wrong threats or species. © 2016 Society for Conservation Biology.

  11. Genome-wide association identifies multiple genomic regions associated with susceptibility to and control of ovine lentivirus.

    Stephen N White

    Full Text Available BACKGROUND: Like human immunodeficiency virus (HIV, ovine lentivirus (OvLV is macrophage-tropic and causes lifelong infection. OvLV infects one quarter of U.S. sheep and induces pneumonia and body condition wasting. There is no vaccine to prevent OvLV infection and no cost-effective treatment for infected animals. However, breed differences in prevalence and proviral concentration have indicated a genetic basis for susceptibility to OvLV. A recent study identified TMEM154 variants in OvLV susceptibility. The objective here was to identify additional loci associated with odds and/or control of OvLV infection. METHODOLOGY/PRINCIPAL FINDINGS: This genome-wide association study (GWAS included 964 sheep from Rambouillet, Polypay, and Columbia breeds with serological status and proviral concentration phenotypes. Analytic models accounted for breed and age, as well as genotype. This approach identified TMEM154 (nominal P=9.2×10(-7; empirical P=0.13, provided 12 additional genomic regions associated with odds of infection, and provided 13 regions associated with control of infection (all nominal P<1 × 10(-5. Rapid decline of linkage disequilibrium with distance suggested many regions included few genes each. Genes in regions associated with odds of infection included DPPA2/DPPA4 (empirical P=0.006, and SYTL3 (P=0.051. Genes in regions associated with control of infection included a zinc finger cluster (ZNF192, ZSCAN16, ZNF389, and ZNF165; P=0.001, C19orf42/TMEM38A (P=0.047, and DLGAP1 (P=0.092. CONCLUSIONS/SIGNIFICANCE: These associations provide targets for mutation discovery in sheep susceptibility to OvLV. Aside from TMEM154, these genes have not been associated previously with lentiviral infection in any species, to our knowledge. Further, data from other species suggest functional hypotheses for future testing of these genes in OvLV and other lentiviral infections. Specifically, SYTL3 binds and may regulate RAB27A, which is required for enveloped

  12. Genome-wide association study of clinically defined gout identifies multiple risk loci and its association with clinical subtypes.

    Matsuo, Hirotaka; Yamamoto, Ken; Nakaoka, Hirofumi; Nakayama, Akiyoshi; Sakiyama, Masayuki; Chiba, Toshinori; Takahashi, Atsushi; Nakamura, Takahiro; Nakashima, Hiroshi; Takada, Yuzo; Danjoh, Inaho; Shimizu, Seiko; Abe, Junko; Kawamura, Yusuke; Terashige, Sho; Ogata, Hiraku; Tatsukawa, Seishiro; Yin, Guang; Okada, Rieko; Morita, Emi; Naito, Mariko; Tokumasu, Atsumi; Onoue, Hiroyuki; Iwaya, Keiichi; Ito, Toshimitsu; Takada, Tappei; Inoue, Katsuhisa; Kato, Yukio; Nakamura, Yukio; Sakurai, Yutaka; Suzuki, Hiroshi; Kanai, Yoshikatsu; Hosoya, Tatsuo; Hamajima, Nobuyuki; Inoue, Ituro; Kubo, Michiaki; Ichida, Kimiyoshi; Ooyama, Hiroshi; Shimizu, Toru; Shinomiya, Nariyoshi

    2016-04-01

    Gout, caused by hyperuricaemia, is a multifactorial disease. Although genome-wide association studies (GWASs) of gout have been reported, they included self-reported gout cases in which clinical information was insufficient. Therefore, the relationship between genetic variation and clinical subtypes of gout remains unclear. Here, we first performed a GWAS of clinically defined gout cases only. A GWAS was conducted with 945 patients with clinically defined gout and 1213 controls in a Japanese male population, followed by replication study of 1048 clinically defined cases and 1334 controls. Five gout susceptibility loci were identified at the genome-wide significance level (pgenes (ABCG2 and SLC2A9) and additional genes: rs1260326 (p=1.9×10(-12); OR=1.36) of GCKR (a gene for glucose and lipid metabolism), rs2188380 (p=1.6×10(-23); OR=1.75) of MYL2-CUX2 (genes associated with cholesterol and diabetes mellitus) and rs4073582 (p=6.4×10(-9); OR=1.66) of CNIH-2 (a gene for regulation of glutamate signalling). The latter two are identified as novel gout loci. Furthermore, among the identified single-nucleotide polymorphisms (SNPs), we demonstrated that the SNPs of ABCG2 and SLC2A9 were differentially associated with types of gout and clinical parameters underlying specific subtypes (renal underexcretion type and renal overload type). The effect of the risk allele of each SNP on clinical parameters showed significant linear relationships with the ratio of the case-control ORs for two distinct types of gout (r=0.96 [p=4.8×10(-4)] for urate clearance and r=0.96 [p=5.0×10(-4)] for urinary urate excretion). Our findings provide clues to better understand the pathogenesis of gout and will be useful for development of companion diagnostics. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

  13. Genome-wide association study in discordant sibships identifies multiple inherited susceptibility alleles linked to lung cancer.

    Galvan, Antonella; Falvella, Felicia S; Frullanti, Elisa; Spinola, Monica; Incarbone, Matteo; Nosotti, Mario; Santambrogio, Luigi; Conti, Barbara; Pastorino, Ugo; Gonzalez-Neira, Anna; Dragani, Tommaso A

    2010-03-01

    We analyzed a series of young (median age = 52 years) non-smoker lung cancer patients and their unaffected siblings as controls, using a genome-wide 620 901 single-nucleotide polymorphism (SNP) array analysis and a case-control DNA pooling approach. We identified 82 putatively associated SNPs that were retested by individual genotyping followed by use of the sib transmission disequilibrium test, pointing to 36 SNPs associated with lung cancer risk in the discordant sibs series. Analysis of these 36 SNPs in a polygenic model characterized by additive and interchangeable effects of rare alleles revealed a highly statistically significant dosage-dependent association between risk allele carrier status and proportion of cancer cases. Replication of the same 36 SNPs in a population-based series confirmed the association with lung cancer for three SNPs, suggesting that phenocopies and genetic heterogeneity can play a major role in the complex genetics of lung cancer risk in the general population.

  14. ApicoAP: the first computational model for identifying apicoplast-targeted proteins in multiple species of Apicomplexa.

    Gokcen Cilingir

    Full Text Available Most of the parasites of the phylum Apicomplexa contain a relict prokaryotic-derived plastid called the apicoplast. This organelle is important not only for the survival of the parasite, but its unique properties make it an ideal drug target. The majority of apicoplast-associated proteins are nuclear encoded and targeted post-translationally to the organellar lumen via a bipartite signaling mechanism that requires an N-terminal signal and transit peptide (TP. Attempts to define a consensus motif that universally identifies apicoplast TPs have failed.In this study, we propose a generalized rule-based classification model to identify apicoplast-targeted proteins (ApicoTPs that use a bipartite signaling mechanism. Given a training set specific to an organism, this model, called ApicoAP, incorporates a procedure based on a genetic algorithm to tailor a discriminating rule that exploits the known characteristics of ApicoTPs. Performance of ApicoAP is evaluated for four labeled datasets of Plasmodium falciparum, Plasmodium yoelii, Babesia bovis, and Toxoplasma gondii proteins. ApicoAP improves the classification accuracy of the published dataset for P. falciparum to 94%, originally 90% using PlasmoAP.We present a parametric model for ApicoTPs and a procedure to optimize the model parameters for a given training set. A major asset of this model is that it is customizable to different parasite genomes. The ApicoAP prediction software is available at http://code.google.com/p/apicoap/ and http://bcb.eecs.wsu.edu.

  15. Identifying Shifts in Leaf-Litter Ant Assemblages (Hymenoptera: Formicidae across Ecosystem Boundaries Using Multiple Sampling Methods.

    Michal Wiezik

    Full Text Available Global or regional environmental changes in climate or land use have been increasingly implied in shifts in boundaries (ecotones between adjacent ecosystems such as beech or oak-dominated forests and forest-steppe ecotones that frequently co-occur near the southern range limits of deciduous forest biome in Europe. Yet, our ability to detect changes in biological communities across these ecosystems, or to understand their environmental drivers, can be hampered when different sampling methods are required to characterize biological communities of the adjacent but ecologically different ecosystems. Ants (Hymenoptera: Formicidae have been shown to be particularly sensitive to changes in temperature and vegetation and they require different sampling methods in closed vs. open habitats. We compared ant assemblages of closed-forests (beech- or oak-dominated and open forest-steppe habitats in southwestern Carpathians using methods for closed-forest (litter sifting and open habitats (pitfall trapping, and developed an integrated sampling approach to characterize changes in ant assemblages across these adjacent ecosystems. Using both methods, we collected 5,328 individual ant workers from 28 species. Neither method represented ant communities completely, but pitfall trapping accounted for more species (24 than litter sifting (16. Although pitfall trapping characterized differences in species richness and composition among the ecosystems better, with beech forest being most species poor and ecotone most species rich, litter sifting was more successful in identifying characteristic litter-dwelling species in oak-dominated forest. The integrated sampling approach using both methods yielded more accurate characterization of species richness and composition, and particularly so in species-rich forest-steppe habitat where the combined sample identified significantly higher number of species compared to either of the two methods on their own. Thus, an integrated

  16. Identifying Shifts in Leaf-Litter Ant Assemblages (Hymenoptera: Formicidae) across Ecosystem Boundaries Using Multiple Sampling Methods.

    Wiezik, Michal; Svitok, Marek; Wieziková, Adela; Dovčiak, Martin

    2015-01-01

    Global or regional environmental changes in climate or land use have been increasingly implied in shifts in boundaries (ecotones) between adjacent ecosystems such as beech or oak-dominated forests and forest-steppe ecotones that frequently co-occur near the southern range limits of deciduous forest biome in Europe. Yet, our ability to detect changes in biological communities across these ecosystems, or to understand their environmental drivers, can be hampered when different sampling methods are required to characterize biological communities of the adjacent but ecologically different ecosystems. Ants (Hymenoptera: Formicidae) have been shown to be particularly sensitive to changes in temperature and vegetation and they require different sampling methods in closed vs. open habitats. We compared ant assemblages of closed-forests (beech- or oak-dominated) and open forest-steppe habitats in southwestern Carpathians using methods for closed-forest (litter sifting) and open habitats (pitfall trapping), and developed an integrated sampling approach to characterize changes in ant assemblages across these adjacent ecosystems. Using both methods, we collected 5,328 individual ant workers from 28 species. Neither method represented ant communities completely, but pitfall trapping accounted for more species (24) than litter sifting (16). Although pitfall trapping characterized differences in species richness and composition among the ecosystems better, with beech forest being most species poor and ecotone most species rich, litter sifting was more successful in identifying characteristic litter-dwelling species in oak-dominated forest. The integrated sampling approach using both methods yielded more accurate characterization of species richness and composition, and particularly so in species-rich forest-steppe habitat where the combined sample identified significantly higher number of species compared to either of the two methods on their own. Thus, an integrated sampling

  17. Simultaneous identification of multiple β-lactamases in Acinetobacter baumannii in relation to carbapenem and ceftazidime resistance, using liquid chromatography-tandem mass spectrometry

    Trip, H.; Mende, K.; Majchrzykiewicz-Koehorst, J.A.; Sedee, N.J.A.; Hulst, A.G.; Jansen, H.J.; Murray, C.K.; Paauw, A.

    2015-01-01

    Shotgun proteomics using liquid chromatography-tandem mass spectrometry (LC-MS/MS) was applied to detect β-lactamases in clinical Acinetobacter baumannii isolates. The correlation of the detection of β-lactamase proteins (rather than PCR detection of the corresponding genes) with the resistance

  18. A targeted sequencing panel identifies rare damaging variants in multiple genes in the cranial neural tube defect, anencephaly.

    Ishida, M; Cullup, T; Boustred, C; James, C; Docker, J; English, C; Lench, N; Copp, A J; Moore, G E; Greene, N D E; Stanier, P

    2018-04-01

    Neural tube defects (NTDs) affecting the brain (anencephaly) are lethal before or at birth, whereas lower spinal defects (spina bifida) may lead to lifelong neurological handicap. Collectively, NTDs rank among the most common birth defects worldwide. This study focuses on anencephaly, which despite having a similar frequency to spina bifida and being the most common type of NTD observed in mouse models, has had more limited inclusion in genetic studies. A genetic influence is strongly implicated in determining risk of NTDs and a molecular diagnosis is of fundamental importance to families both in terms of understanding the origin of the condition and for managing future pregnancies. Here we used a custom panel of 191 NTD candidate genes to screen 90 patients with cranial NTDs (n = 85 anencephaly and n = 5 craniorachischisis) with a targeted exome sequencing platform. After filtering and comparing to our in-house control exome database (N = 509), we identified 397 rare variants (minor allele frequency, MAF < 1%), 21 of which were previously unreported and predicted damaging. This included 1 frameshift (PDGFRA), 2 stop-gained (MAT1A; NOS2) and 18 missense variations. Together with evidence for oligogenic inheritance, this study provides new information on the possible genetic causation of anencephaly. © 2017 The Authors. Clinical Genetics published by John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  19. Application of multiple tracers (SF6 and chloride) to identify the transport by characteristics of contaminant at two separate contaminated sites

    Lee, K. K.; Lee, S. S.; Kim, H. H.; Koh, E. H.; Kim, M. O.; Lee, K.; Kim, H. J.

    2016-12-01

    Multiple tracers were applied for source and pathway detection at two different sites. CO2 gas injected in the subsurface for a shallow-depth CO2 injection and leak test can be regarded as a potential contaminant source. Therefore, it is necessary to identify the migration pattern of CO2 gas. Also, at a DNAPL contaminated site, it is important to figure out the characteristics of plume evolution from the source zone. In this study, multiple tracers (SF6 and chloride) were used to evaluate the applicability of volatile and non-volatile tracers and to identify the characteristics of contaminant transport at each CO2 injection and leak test site and DNAPL contaminated site. Firstly, at the CO2 test site, multiple tracers were used to perform the single well push-drift-pull tracer test at total 3 specific depth zones. As results of tests, volatile and non-volatile tracers showed different mass recovery percentage. Most of chloride mass was recovered but less than half of SF6 mass was recovered due to volatile property. This means that only gaseous SF6 leak out to unsaturated zone. However, breakthrough curves of both tracers indicated similar peak time, effective porosity, and regional groundwater velocity. Also, at both contaminated sites, natural gradient tracer tests were performed with multiple tracers. With the results of natural gradient tracer test, it was possible to confirm the applicability of multiple tracers and to understand the contaminant transport in highly heterogeneous aquifer systems through the long-term monitoring of tracers. Acknowledgement: financial support was provided by the R&D Project on Environmental Management of Geologic CO2 Storage)" from the KEITI (Project Number: 2014001810003) and Korea Ministry of Environment as "The GAIA project (2014000540010)".

  20. Multiple lines of evidence to identify sewage as the cause of water quality impairment in an urbanized tropical watershed.

    Kirs, Marek; Kisand, Veljo; Wong, Mayee; Caffaro-Filho, Roberto A; Moravcik, Philip; Harwood, Valerie J; Yoneyama, Bunnie; Fujioka, Roger S

    2017-06-01

    Indicator bacteria, which are conventionally used to evaluate recreational water quality, can originate from various non-human enteric and extra-enteric sources, hence they may not be indicative of human health risk nor do they provide information on the sources of contamination. In this study we utilized traditional (enterococci and Escherichia coli) and alternative (Clostridium perfringens) indicator bacteria, F + -specific coliphage, molecular markers for microorganisms associated with human sewage (human-associated Bacteroides and polyomaviruses), and microbial community analysis tools (16S rRNA gene fragment amplicon sequencing), to identify and evaluate human sewage-related impact in the Manoa watershed in Honolulu, Hawaii. Elevated concentrations of enterococci (geometric mean ranging from 1604 to 2575 CFU 100 mL -1 ) and C. perfringens (45-77 CFU 100 mL -1 ) indicated impairment of the urbanized section of the stream, while indicator bacteria concentrations decreased downstream in the tidally influenced Ala Wai Canal. The threshold values triggering water quality violation notifications in Hawaii were exceeded in 33.3-75.0% of samples collected at sites in the urbanized section of Manoa Stream, but were not exceeded in any of the samples collected at an upstream site located in a forested area. Correlation between indicator bacteria concentrations and rainfall amounts was weak to moderate but significant (E. coli R = 0.251, P = 0.009; enterococci R = 0.369, P watershed, it was lower in the impaired section. Leaking sewer systems and illegal cross-connections are implicated in the impairment of the watershed, hence both the sewer and the storm water lines should be routinely inspected. Collectively, our data suggest that information derived from the analysis of microbial communities complements current marker-based microbial source tracking techniques and environmental monitoring programs. Copyright © 2017 Elsevier Ltd. All rights reserved.

  1. Metabolites of 5F-AKB-48, a synthetic cannabinoid receptor agonist, identified in human urine and liver microsomal preparations using liquid chromatography high-resolution mass spectrometry

    Holm, Niels Bjerre; Pedersen, Anders Just; Dalsgaard, Petur Weihe

    2015-01-01

    New types of synthetic cannabinoid designer drugs are constantly introduced to the illicit drug market to circumvent legislation. Recently, N-​(1-Adamant​yl)-​1-​(5-​fluoropentyl)-​1H-​indazole-​3-​carboxamide (5F-AKB-48), also known as 5F-APINACA, was identified as an adulterant in herbal products...

  2. Simultaneously combining AOD and multiple trace gas measurements to identify decadal changes in urban and biomass burning aerosols

    Cohen, Jason

    2017-04-01

    This work presents a methodology by which to comprehensively analyze simultaneous tropospheric measurements of AOD and associated trace gasses. It then applies this methodology by focusing over the past 11 years (2006-2016) on one of the most rapidly changing regions of the troposphere: Eastern and Southeastern Asia. The specific work presented incorporates measurements of both aerosol and related gas phase tropospheric measurements across different spectral, spatial, temporal, and passive/active sensors and properties, including: MODIS, MISR, OMI, CALIOP, and others. This new characterization reveals a trio of new information, including a time-invariant urban signal, slowly-time-varying new-urbanization signal, and a rapidly time-varying biomass burning signal. Additionally, due to the different chemical properties of the various species analyzed, analyzing the different spatial domains of the resulting products allows for further information in terms of the amounts of aerosols produced both through primary emissions as well as secondary processing. The end result is a new characterization, in space, time, and magnitude, of both anthropogenic and biomass burning aerosols. These results are then used to drive an advanced modeling system including aerosol chemistry, physics, optics, and transport, and employing an aerosol routine based on multi-modal and both externally mixed and core-shell mixing. The resulting characterization in space, time, and quantity is analyzed and compared against AERONET, NOAA, and other ground networks, with the results comparing consistently to or better than present approaches which set up net emissions separately from urban and biomass burning products. Scientifically, new source regions of emissions are identified, some of which were previously non-urbanized or found to not contain any fire hotspots. This new approach is consistent with the underlying economic and development pathways of expanding urban areas and rapid economic growth

  3. Identifying Topics for E-Cigarette User-Generated Contents: A Case Study From Multiple Social Media Platforms.

    Zhan, Yongcheng; Liu, Ruoran; Li, Qiudan; Leischow, Scott James; Zeng, Daniel Dajun

    2017-01-20

    Electronic cigarette (e-cigarette) is an emerging product with a rapid-growth market in recent years. Social media has become an important platform for information seeking and sharing. We aim to mine hidden topics from e-cigarette datasets collected from different social media platforms. This paper aims to gain a systematic understanding of the characteristics of various types of social media, which will provide deep insights into how consumers and policy makers effectively use social media to track e-cigarette-related content and adjust their decisions and policies. We collected data from Reddit (27,638 e-cigarette flavor-related posts from January 1, 2011, to June 30, 2015), JuiceDB (14,433 e-juice reviews from June 26, 2013 to November 12, 2015), and Twitter (13,356 "e-cig ban"-related tweets from January, 1, 2010 to June 30, 2015). Latent Dirichlet Allocation, a generative model for topic modeling, was used to analyze the topics from these data. We found four types of topics across the platforms: (1) promotions, (2) flavor discussions, (3) experience sharing, and (4) regulation debates. Promotions included sales from vendors to users, as well as trades among users. A total of 10.72% (2,962/27,638) of the posts from Reddit were related to trading. Promotion links were found between social media platforms. Most of the links (87.30%) in JuiceDB were related to Reddit posts. JuiceDB and Reddit identified consistent flavor categories. E-cigarette vaping methods and features such as steeping, throat hit, and vapor production were broadly discussed both on Reddit and on JuiceDB. Reddit provided space for policy discussions and majority of the posts (60.7%) holding a negative attitude toward regulations, whereas Twitter was used to launch campaigns using certain hashtags. Our findings are based on data across different platforms. The topic distribution between Reddit and JuiceDB was significantly different (Puser discussions focused on different perspectives across the

  4. Development of the policy indicator checklist: a tool to identify and measure policies for calorie-dense foods and sugar-sweetened beverages across multiple settings.

    Lee, Rebecca E; Hallett, Allen M; Parker, Nathan; Kudia, Ousswa; Kao, Dennis; Modelska, Maria; Rifai, Hanadi; O'Connor, Daniel P

    2015-05-01

    We developed the policy indicator checklist (PIC) to identify and measure policies for calorie-dense foods and sugar-sweetened beverages to determine how policies are clustered across multiple settings. In 2012 and 2013 we used existing literature, policy documents, government recommendations, and instruments to identify key policies. We then developed the PIC to examine the policy environments across 3 settings (communities, schools, and early care and education centers) in 8 communities participating in the Childhood Obesity Research Demonstration Project. Principal components analysis revealed 5 components related to calorie-dense food policies and 4 components related to sugar-sweetened beverage policies. Communities with higher youth and racial/ethnic minority populations tended to have fewer and weaker policy environments concerning calorie-dense foods and healthy foods and beverages. The PIC was a helpful tool to identify policies that promote healthy food environments across multiple settings and to measure and compare the overall policy environments across communities. There is need for improved coordination across settings, particularly in areas with greater concentration of youths and racial/ethnic minority populations. Policies to support healthy eating are not equally distributed across communities, and disparities continue to exist in nutrition policies.

  5. Physical activity and exercise training in multiple sclerosis: a review and content analysis of qualitative research identifying perceived determinants and consequences.

    Learmonth, Yvonne C; Motl, Robert W

    2016-01-01

    This systematic review was conducted to provide rich and deep evidence of the perceived determinants and consequences of physical activity and exercise based on qualitative research in multiple sclerosis (MS). Electronic databases and article reference lists were searched to identify qualitative studies of physical activity and exercise in MS. Studies were included if they were written in English and examined consequences/determinants of physical activity in persons with MS. Content analysis of perceived determinants and consequences of physical activity and exercise was undertaken using an inductive analysis guided by the Physical Activity for people with Disabilities framework and Social Cognitive Theory, respectively. Nineteen articles were reviewed. The most commonly identified perceived barriers of physical activity and exercise were related to the environmental (i.e. minimal or no disabled facilities, and minimal or conflicting advice from healthcare professionals) and related to personal barriers (i.e. fatigue, and fear and apprehension). The most commonly identified perceived facilitators of physical activity were related to the environment (i.e. the type of exercise modality and peer support) and related to personal facilitators (i.e. appropriate exercise and feelings of accomplishment). The most commonly identified perceived beneficial consequences of physical activity and exercise were maintaining physical functions, increased social participation and feelings of self-management and control. The most commonly identified perceived adverse consequences were increased fatigue and feelings of frustration and lost control. Results will inform future research on the perceived determinants and consequences of physical activity and exercise in those with MS and can be adopted for developing professional education and interventions for physical activity and exercise in MS. Physical activity and exercise behaviour in people with multiple sclerosis (MS) is subject

  6. Nuclear magnetic resonance and liquid chromatography-mass spectrometry combined with an incompleted separation strategy for identifying the natural products in crude extract

    Dai Dongmei; He Jiuming [Key Laboratory of Bioactive Substances and Resource Utilization of Chinese Herbal Medicine, Ministry of Education, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, 1 Xian Nong Tan Street, Beijing 100050 (China); Sun Ruixiang [Institute of Computing Technology, Chinese Academy of Sciences, Beijing 100080 (China); Zhang Ruiping [Key Laboratory of Bioactive Substances and Resource Utilization of Chinese Herbal Medicine, Ministry of Education, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, 1 Xian Nong Tan Street, Beijing 100050 (China); Aisa, Haji Akber [Xinjiang Technological Institute of Physics and Chemistry, Chinese Academy of Sciences, Urumqi 830011 (China); Abliz, Zeper [Key Laboratory of Bioactive Substances and Resource Utilization of Chinese Herbal Medicine, Ministry of Education, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, 1 Xian Nong Tan Street, Beijing 100050 (China)], E-mail: zeper@imm.ac.cn

    2009-01-26

    NMR and LC-MS combined with an incompleted separation strategy were proposed to the simultaneous structure identification of natural products in crude extracts, and a novel method termed as NMR/LC-MS parallel dynamic spectroscopy (NMR/LC-MS PDS) was developed to discover the intrinsic correlation between retention time (Rt), mass/charge (m/z) and chemical shift ({delta}) data of the same constituent from mixture spectra by the co-analysis of parallelly visualized multispectroscopic datasets from LC-MS and {sup 1}H NMR. The extracted ion chromatogram (XIC) and {sup 1}H NMR signals deriving from the same individual constituent were correlated through fraction ranges and intensity changing profiles in NMR/LC-MS PDS spectrum due to the signal amplitude co-variation resulted from the concentration variation of constituents in a series of incompletely separated fractions. NMR/LC-MS PDS was applied to identify 12 constituents in an active herbal extract including flavonol glycosides, which was separated into a series of fractions by flash column chromatography. The complementary spectral information of the same individual constituent in the crude extract was discovered simultaneously from mixture spectra. Especially, two groups of co-eluted isomers were identified successfully. The results demonstrated that NMR/LC-MS PDS combined with the incompleted separation strategy achieved the similar function of on-line LC-NMR-MS analysis in off-line mode and had the potential for simplifying and accelerating the analytical routes for structure identification of constituents in herbs or their active extracts.

  7. Nuclear magnetic resonance and liquid chromatography-mass spectrometry combined with an incompleted separation strategy for identifying the natural products in crude extract

    Dai Dongmei; He Jiuming; Sun Ruixiang; Zhang Ruiping; Aisa, Haji Akber; Abliz, Zeper

    2009-01-01

    NMR and LC-MS combined with an incompleted separation strategy were proposed to the simultaneous structure identification of natural products in crude extracts, and a novel method termed as NMR/LC-MS parallel dynamic spectroscopy (NMR/LC-MS PDS) was developed to discover the intrinsic correlation between retention time (Rt), mass/charge (m/z) and chemical shift (δ) data of the same constituent from mixture spectra by the co-analysis of parallelly visualized multispectroscopic datasets from LC-MS and 1 H NMR. The extracted ion chromatogram (XIC) and 1 H NMR signals deriving from the same individual constituent were correlated through fraction ranges and intensity changing profiles in NMR/LC-MS PDS spectrum due to the signal amplitude co-variation resulted from the concentration variation of constituents in a series of incompletely separated fractions. NMR/LC-MS PDS was applied to identify 12 constituents in an active herbal extract including flavonol glycosides, which was separated into a series of fractions by flash column chromatography. The complementary spectral information of the same individual constituent in the crude extract was discovered simultaneously from mixture spectra. Especially, two groups of co-eluted isomers were identified successfully. The results demonstrated that NMR/LC-MS PDS combined with the incompleted separation strategy achieved the similar function of on-line LC-NMR-MS analysis in off-line mode and had the potential for simplifying and accelerating the analytical routes for structure identification of constituents in herbs or their active extracts

  8. HAMS: High-Affinity Mass Spectrometry Screening. A High-Throughput Screening Method for Identifying the Tightest-Binding Lead Compounds for Target Proteins with No False Positive Identifications.

    Imaduwage, Kasun P; Go, Eden P; Zhu, Zhikai; Desaire, Heather

    2016-11-01

    A major challenge in drug discovery is the identification of high affinity lead compounds that bind a particular target protein; these leads are typically identified by high throughput screens. Mass spectrometry has become a detection method of choice in drug screening assays because the target and the ligand need not be modified. Label-free assays are advantageous because they can be developed more rapidly than assays requiring labels, and they eliminate the risk of the label interfering with the binding event. However, in commonly used MS-based screening methods, detection of false positives is a major challenge. Here, we describe a detection strategy designed to eliminate false positives. In this approach, the protein and the ligands are incubated together, and the non-binders are separated for detection. Hits (protein binders) are not detectable by MS after incubation with the protein, but readily identifiable by MS when the target protein is not present in the incubation media. The assay was demonstrated using three different proteins and hundreds of non-inhibitors; no false positive hits were identified in any experiment. The assay can be tuned to select for ligands of a particular binding affinity by varying the quantity of protein used and the immobilization method. As examples, the method selectively detected inhibitors that have K i values of 0.2 μM, 50 pM, and 700 pM. These findings demonstrate that the approach described here compares favorably with traditional MS-based screening methods. Graphical Abstract ᅟ.

  9. Nontargeted SWATH acquisition for identifying 47 synthetic cannabinoid metabolites in human urine by liquid chromatography-high-resolution tandem mass spectrometry.

    Scheidweiler, Karl B; Jarvis, Michael J Y; Huestis, Marilyn A

    2015-01-01

    Clandestine laboratories constantly produce new synthetic cannabinoids to circumvent legislative scheduling efforts, challenging and complicating toxicological analysis. Sundstrom et al. (Anal Bioanal Chem 405(26):8463-8474, [9]) and Kronstrand et al. (Anal Bioanal Chem 406(15):3599-3609, [10]) published nontargeted liquid chromatography, high-resolution, quadrupole/time-of-flight mass spectrometric (LC-QTOF) assays with validated detection of 18 and 38 urinary synthetic cannabinoid metabolites, respectively. We developed and validated a LC-QTOF urine method for simultaneously identifying the most current 47 synthetic cannabinoid metabolites from 21 synthetic cannabinoid families (5-fluoro AB-PINACA, 5-fluoro-AKB48, 5-fluoro PB-22, AB-PINACA, ADB-PINACA, AKB48, AM2201, JWH-018, JWH-019, JWH-073, JWH-081, JWH-122, JWH-200, JWH-210, JWH-250, JWH-398, MAM2201, PB-22, RCS-4, UR-144, and XLR11). β-Glucuronidase-hydrolyzed urine was extracted with 1-mL Biotage SLE+ columns. Specimens were reconstituted in 150-μL mobile phase consisting of 80% A (0.1% formic acid in water) and 20% B (0.1% formic acid in acetonitrile). Fifty microliters was injected, and SWATH™ MS data were acquired in positive electrospray mode. The LC-QTOF instrument consisted of a Shimadzu UFLCxr system and an ABSciex 5600+ TripleTOF® mass spectrometer. Gradient chromatographic separation was achieved with a Restek Ultra Biphenyl column with a 0.5-mL/min flow rate and an overall run time of 15 min. Identification criteria included molecular ion mass error, isotopic profiles, retention time, and library fit criteria. Limits of detection were 0.25-5 μg/L (N = 10 unique fortified urine samples), except for two PB-22 metabolites with limits of 10 and 20 μg/L. Extraction efficiencies and matrix effects (N = 10) were 55-104 and -65-107%, respectively. We present a highly useful novel LC-QTOF method for simultaneously confirming 47 synthetic cannabinoid metabolites in human urine.

  10. Recurrent TERT promoter mutations identified in a large-scale study of multiple tumor types are associated with increased TERT expression and telomerase activation

    Huang, Dong-Sheng; Wang, Zhaohui; He, Xu-Jun; Diplas, Bill H.; Yang, Rui; Killela, Patrick J.; Liang, Junbo; Meng, Qun; Ye, Zai-Yuan; Wang, Wei; Jiang, Xiao-Ting; Xu, Li; He, Xiang-Lei; Zhao, Zhong-Sheng; Xu, Wen-Juan; Wang, Hui-Ju; Ma, Ying-Yu; Xia, Ying-Jie; Li, Li; Zhang, Ru-Xuan; Jin, Tao; Zhao, Zhong-Kuo; Xu, Ji; Yu, Sheng; Wu, Fang; Wang, Si-Zhen; Jiao, Yu-Chen; Yan, Hai; Tao, Hou-Quan

    2015-01-01

    Background Several somatic mutation hotspots were recently identified in the TERT promoter region in human cancers. Large scale studies of these mutations in multiple tumor types are limited, in particular in Asian populations. This study aimed to: analyze TERT promoter mutations in multiple tumor types in a large Chinese patient cohort, investigate novel tumor types and assess the functional significance of the mutations. Methods TERT promoter mutation status was assessed by Sanger sequencing for 13 different tumor types and 799 tumor tissues from Chinese cancer patients. Thymic epithelial tumors, gastrointestinal leiomyoma, and gastric schwannoma were included, for which the TERT promoter has not been previously sequenced. Functional studies included TERT expression by RT-qPCR, telomerase activity by the TRAP assay, and promoter activity by the luciferase reporter assay. Results TERT promoter mutations were highly frequent in glioblastoma (83.9%), urothelial carcinoma (64.5%), oligodendroglioma (70.0%), medulloblastoma (33.3%), and hepatocellular carcinoma (31.4%). C228T and C250T were the most common mutations. In urothelial carcinoma, several novel rare mutations were identified. TERT promoter mutations were absent in GIST, thymic epithelial tumors, gastrointestinal leiomyoma, gastric schwannoma, cholangiocarcinoma, gastric and pancreatic cancer. TERT promoter mutations highly correlated with upregulated TERT mRNA expression and telomerase activity in adult gliomas. These mutations differentially enhanced the transcriptional activity of the TERT core promoter. Conclusions TERT promoter mutations are frequent in multiple tumor types and have similar distributions in Chinese cancer patients. The functional significance of these mutations reflect the importance to telomere maintenance and hence tumorigenesis, making them potential therapeutic targets. PMID:25843513

  11. Combination of Multiple Spectral Libraries Improves the Current Search Methods Used to Identify Missing Proteins in the Chromosome-Centric Human Proteome Project.

    Cho, Jin-Young; Lee, Hyoung-Joo; Jeong, Seul-Ki; Kim, Kwang-Youl; Kwon, Kyung-Hoon; Yoo, Jong Shin; Omenn, Gilbert S; Baker, Mark S; Hancock, William S; Paik, Young-Ki

    2015-12-04

    Approximately 2.9 billion long base-pair human reference genome sequences are known to encode some 20 000 representative proteins. However, 3000 proteins, that is, ~15% of all proteins, have no or very weak proteomic evidence and are still missing. Missing proteins may be present in rare samples in very low abundance or be only temporarily expressed, causing problems in their detection and protein profiling. In particular, some technical limitations cause missing proteins to remain unassigned. For example, current mass spectrometry techniques have high limits and error rates for the detection of complex biological samples. An insufficient proteome coverage in a reference sequence database and spectral library also raises major issues. Thus, the development of a better strategy that results in greater sensitivity and accuracy in the search for missing proteins is necessary. To this end, we used a new strategy, which combines a reference spectral library search and a simulated spectral library search, to identify missing proteins. We built the human iRefSPL, which contains the original human reference spectral library and additional peptide sequence-spectrum match entries from other species. We also constructed the human simSPL, which contains the simulated spectra of 173 907 human tryptic peptides determined by MassAnalyzer (version 2.3.1). To prove the enhanced analytical performance of the combination of the human iRefSPL and simSPL methods for the identification of missing proteins, we attempted to reanalyze the placental tissue data set (PXD000754). The data from each experiment were analyzed using PeptideProphet, and the results were combined using iProphet. For the quality control, we applied the class-specific false-discovery rate filtering method. All of the results were filtered at a false-discovery rate of libraries, iRefSPL and simSPL, were designed to ensure no overlap of the proteome coverage. They were shown to be complementary to spectral library

  12. Application of a new procedure for liquid chromatography/mass spectrometry profiling of plasma amino acid-related metabolites and untargeted shotgun proteomics to identify mechanisms and biomarkers of calcific aortic stenosis.

    Olkowicz, Mariola; Debski, Janusz; Jablonska, Patrycja; Dadlez, Michal; Smolenski, Ryszard T

    2017-09-29

    Calcific aortic valve stenosis (CAS) increasingly affects our ageing population, but the mechanisms of the disease and its biomarkers are not well established. Recently, plasma amino acid-related metabolite (AA) profiling has attracted attention in studies on pathology and development of biomarkers of cardiovascular diseases, but has not been studied in CAS. To evaluate the potential relationship between CAS and AA metabolome, a new ion-pairing reversed-phase liquid chromatography-tandem mass spectrometry (IP-RPLC-MS/MS) method has been developed and validated for simultaneous determination of 43 AAs in plasma of stenotic patients and age-matched control subjects. Furthermore, untargeted mass spectrometry-based proteomic analysis and confirmatory ELISA assays were performed. The method developed offered high accuracy (intra-assay imprecision averaged 4.4% for all compounds) and sensitivity (LOQ within 0.01-0.5μM). We found that 22 AAs and three AA ratios significantly changed in the CAS group as compared to control. The most pronounced differences were observed in urea cycle-related AAs and branched-chain AA (BCAA)-related AAs. The contents of asymmetric dimethylarginine (ADMA) and its monomethylated derivative (NMMA) were increased by 30-64% with CAS. The arginine/ADMA and Fischer's ratios as well as arginine, homoarginine, ADMA, symmetric dimethylarginine, hydroxyproline, betaine and 3-methylhistidine correlated with cardiac function-related parameters and concomitant systemic factors in the CAS patients. The results of proteomic analysis were consistent with involvement of inflammation, lipid abnormalities, hemostasis and extracellular matrix remodeling in CAS. In conclusion, changes in plasma AA profile and protein pattern that we identified in CAS provide information relevant to pathomechanisms and may deliver new biomarkers of the disease. Copyright © 2017 Elsevier B.V. All rights reserved.

  13. The use of selective adsorbents in capillary electrophoresis-mass spectrometry for analyte preconcentration and microreactions: a powerful three-dimensional tool for multiple chemical and biological applications.

    Guzman, N A; Stubbs, R J

    2001-10-01

    Much attention has recently been directed to the development and application of online sample preconcentration and microreactions in capillary electrophoresis using selective adsorbents based on chemical or biological specificity. The basic principle involves two interacting chemical or biological systems with high selectivity and affinity for each other. These molecular interactions in nature usually involve noncovalent and reversible chemical processes. Properly bound to a solid support, an "affinity ligand" can selectively adsorb a "target analyte" found in a simple or complex mixture at a wide range of concentrations. As a result, the isolated analyte is enriched and highly purified. When this affinity technique, allowing noncovalent chemical interactions and biochemical reactions to occur, is coupled on-line to high-resolution capillary electrophoresis and mass spectrometry, a powerful tool of chemical and biological information is created. This paper describes the concept of biological recognition and affinity interaction on-line with high-resolution separation, the fabrication of an "analyte concentrator-microreactor", optimization conditions of adsorption and desorption, the coupling to mass spectrometry, and various applications of clinical and pharmaceutical interest.

  14. Source-identifying biomarker ions between environmental and clinical Burkholderia pseudomallei using whole-cell matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS).

    Niyompanich, Suthamat; Jaresitthikunchai, Janthima; Srisanga, Kitima; Roytrakul, Sittiruk; Tungpradabkul, Sumalee

    2014-01-01

    Burkholderia pseudomallei is the causative agent of melioidosis, which is an endemic disease in Northeast Thailand and Northern Australia. Environmental reservoirs, including wet soils and muddy water, serve as the major sources for contributing bacterial infection to both humans and animals. The whole-cell matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (whole-cell MALDI-TOF MS) has recently been applied as a rapid, accurate, and high-throughput tool for clinical diagnosis and microbiological research. In this present study, we employed a whole-cell MALDI-TOF MS approach for assessing its potency in clustering a total of 11 different B. pseudomallei isolates (consisting of 5 environmental and 6 clinical isolates) with respect to their origins and to further investigate the source-identifying biomarker ions belonging to each bacterial group. The cluster analysis demonstrated that six out of eleven isolates were grouped correctly to their sources. Our results revealed a total of ten source-identifying biomarker ions, which exhibited statistically significant differences in peak intensity between average environmental and clinical mass spectra using ClinProTools software. Six out of ten mass ions were assigned as environmental-identifying biomarker ions (EIBIs), including, m/z 4,056, 4,214, 5,814, 7,545, 7,895, and 8,112, whereas the remaining four mass ions were defined as clinical-identifying biomarker ions (CIBIs) consisting of m/z 3,658, 6,322, 7,035, and 7,984. Hence, our findings represented, for the first time, the source-specific biomarkers of environmental and clinical B. pseudomallei.

  15. 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

    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

  16. Enriching an intraspecific genetic map and identifying QTL for fiber quality and yield component traits across multiple environments in Upland cotton (Gossypium hirsutum L.).

    Liu, Xueying; Teng, Zhonghua; Wang, Jinxia; Wu, Tiantian; Zhang, Zhiqin; Deng, Xianping; Fang, Xiaomei; Tan, Zhaoyun; Ali, Iftikhar; Liu, Dexin; Zhang, Jian; Liu, Dajun; Liu, Fang; Zhang, Zhengsheng

    2017-12-01

    Cotton is a significant commercial crop that plays an indispensable role in many domains. Constructing high-density genetic maps and identifying stable quantitative trait locus (QTL) controlling agronomic traits are necessary prerequisites for marker-assisted selection (MAS). A total of 14,899 SSR primer pairs designed from the genome sequence of G. raimondii were screened for polymorphic markers between mapping parents CCRI 35 and Yumian 1, and 712 SSR markers showing polymorphism were used to genotype 180 lines from a (CCRI 35 × Yumian 1) recombinant inbred line (RIL) population. Genetic linkage analysis was conducted on 726 loci obtained from the 712 polymorphic SSR markers, along with 1379 SSR loci obtained in our previous study, and a high-density genetic map with 2051 loci was constructed, which spanned 3508.29 cM with an average distance of 1.71 cM between adjacent markers. Marker orders on the linkage map are highly consistent with the corresponding physical orders on a G. hirsutum genome sequence. Based on fiber quality and yield component trait data collected from six environments, 113 QTLs were identified through two analytical methods. Among these 113 QTLs, 50 were considered stable (detected in multiple environments or for which phenotypic variance explained by additive effect was greater than environment effect), and 18 of these 50 were identified with stability by both methods. These 18 QTLs, including eleven for fiber quality and seven for yield component traits, could be priorities for MAS.

  17. Therapeutic molecules for multiple human diseases identified from pigeon pea (Cajanus cajan L. Millsp. through GC–MS and molecular docking

    Deepu Mathew

    2017-12-01

    Full Text Available Molecular mechanism behind the therapeutic potential of pigeon pea over the human diseases such as rheumatoid arthritis, breast cancer, type II diabetes, malaria, measles and sickle cell disease were revealed through docking of GC–MS identified phyto-compound ligands with candidate disease proteins. Of the 242 ligands, three dimensional structures of 47 compounds had to be drawn using ChemSketch and the remaining structures were retrieved from PubChem and docked with the active sites of candidate proteins. The molecules identified through docking were further subjected to ADMET analysis and promising drug candidates were identified for each disease. This paper presents a precise account of the chemoprofile of pigeon pea leaves, stems and seeds, interaction of these molecules with target proteins and suggests 26 highly potential molecules which are drug candidates for multiple human diseases. Pigeon pea seeds are especially proven as invaluable source for therapeutic molecules. Keywords: Breast cancer, Drug discovery, Herbal medicine, In silico, Malaria, Measles, Phyto-compounds, Rheumatoid arthritis, Sickle cell disease, Type II diabetes

  18. Identifying Patient-Specific Epstein-Barr Nuclear Antigen-1 Genetic Variation and Potential Autoreactive Targets Relevant to Multiple Sclerosis Pathogenesis.

    Monika Tschochner

    Full Text Available Epstein-Barr virus (EBV infection represents a major environmental risk factor for multiple sclerosis (MS, with evidence of selective expansion of Epstein-Barr Nuclear Antigen-1 (EBNA1-specific CD4+ T cells that cross-recognize MS-associated myelin antigens in MS patients. HLA-DRB1*15-restricted antigen presentation also appears to determine susceptibility given its role as a dominant risk allele. In this study, we have utilised standard and next-generation sequencing techniques to investigate EBNA-1 sequence variation and its relationship to HLA-DR15 binding affinity, as well as examining potential cross-reactive immune targets within the central nervous system proteome.Sanger sequencing was performed on DNA isolated from peripheral blood samples from 73 Western Australian MS cases, without requirement for primary culture, with additional FLX 454 Roche sequencing in 23 samples to identify low-frequency variants. Patient-derived viral sequences were used to predict HLA-DRB1*1501 epitopes (NetMHCII, NetMHCIIpan and candidates were evaluated for cross recognition with human brain proteins.EBNA-1 sequence variation was limited, with no evidence of multiple viral strains and only low levels of variation identified by FLX technology (8.3% nucleotide positions at a 1% cut-off. In silico epitope mapping revealed two known HLA-DRB1*1501-restricted epitopes ('AEG': aa 481-496 and 'MVF': aa 562-577, and two putative epitopes between positions 502-543. We identified potential cross-reactive targets involving a number of major myelin antigens including experimentally confirmed HLA-DRB1*15-restricted epitopes as well as novel candidate antigens within myelin and paranodal assembly proteins that may be relevant to MS pathogenesis.This study demonstrates the feasibility of obtaining autologous EBNA-1 sequences directly from buffy coat samples, and confirms divergence of these sequences from standard laboratory strains. This approach has identified a number of

  19. Mass spectrometry

    Nyvang Hartmeyer, Gitte; Jensen, Anne Kvistholm; Böcher, Sidsel

    2010-01-01

    Matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) is currently being introduced for the rapid and accurate identification of bacteria. We describe 2 MALDI-TOF MS identification cases - 1 directly on spinal fluid and 1 on grown bacteria. Rapidly obtained...

  20. Identifying preferred format and source of exercise information in persons with multiple sclerosis that can be delivered by health-care providers.

    Learmonth, Yvonne C; Adamson, Brynn C; Balto, Julia M; Chiu, Chung-Yi; Molina-Guzman, Isabel M; Finlayson, Marcia; Riskin, Barry J; Motl, Robert W

    2017-10-01

    There is increasing recognition of the benefits of exercise in individuals with multiple sclerosis (MS), yet the MS population does not engage in sufficient amounts of exercise to accrue health benefits. There has been little qualitative inquiry to establish the preferred format and source for receiving exercise information from health-care providers among persons with MS. We sought to identify the desired and preferred format and source of exercise information for persons with MS that can be delivered through health-care providers. Participants were adults with MS who had mild or moderate disability and participated in a range of exercise levels. All participants lived in the Midwest of the United States. Fifty semi-structured interviews were conducted and analysed using thematic analysis. Two themes emerged, (i) approach for receiving exercise promotion and (ii) ideal person for promoting exercise. Persons with MS want to receive exercise information through in-person consultations with health-care providers, print media and electronic media. Persons with MS want to receive exercise promotion from health-care providers with expertise in MS (ie neurologists) and with expertise in exercise (eg physical therapists). These data support the importance of understanding how to provide exercise information to persons with MS and identifying that health-care providers including neurologists and physical therapists should be involved in exercise promotion. © 2017 The Authors Health Expectations Published by John Wiley & Sons Ltd.

  1. Microorganisms in cryopreserved semen and culture media used in the in vitro production (IVP) of bovine embryos identified by matrix-assisted laser desorption ionization mass spectrometry (MALDI-MS).

    Zampieri, Dávila; Santos, Vanessa G; Braga, Patrícia A C; Ferreira, Christina R; Ballottin, Daniela; Tasic, Ljubica; Basso, Andréa C; Sanches, Bruno V; Pontes, José H F; da Silva, Bárbara Pereira; Garboggini, Fabiana Fantinatti; Eberlin, Marcos N; Tata, Alessandra

    2013-09-01

    Commercial cattle breeders produce their own herd offspring for the dairy and beef market using artificial insemination. The procedure involves sanitary risks associated with the collection and commercialization of the germplasm, and the in vitro production and transfer of the bovine embryos must be monitored by strict health surveillance. To avoid the spreading of infectious diseases, one must rely on using controlled and monitored germplasm, media, and reagents that are guaranteed free of pathogens. In this article, we investigated the use of a new mass spectrometric approach for fast and accurate identification of bacteria and fungi in bovine semen and in culture media employed in the embryo in vitro production process. The microorganisms isolated from samples obtained in a commercial bovine embryo IVP setting were identified in a few minutes by their conserved peptide/protein profile, obtained applying matrix-assisted laser desorption ionization mass spectrometry (MALDI-MS), matched against a commercial database. The successful microorganisms MS identification has been confirmed by DNA amplification and sequencing. Therefore, the MS technique seems to offer a powerful tool for rapid and accurate microorganism identification in semen and culture media samples. Copyright © 2013 Elsevier Inc. All rights reserved.

  2. COMPARISON OF IMMUNOASSAY AND GAS CHROMATOGRAPHY/MASS SPECTROMETRY METHODS FOR MEASURING 3,5,6-TRICHLORO-2PYRIDINOL IN MULTIPLE SAMPLE MEDIA

    Two enzyme-linked immunosorbent assay (ELISA) methods were evaluated for the determination of 3,5,6-trichloro-2-pyridinol (3,5,6-TCP) in multiple sample media (dust, soil, food, and urine). The dust and soil samples were analyzed by a commercial RaPID immunoassay testing kit. ...

  3. High-Throughput Proteomics Using High Efficiency Multiple-Capillary Liquid Chromatography With On-Line High-Performance ESI FTICR Mass Spectrometry

    Shen, Yufeng (BATTELLE (PACIFIC NW LAB)); Tolic, Nikola (BATTELLE (PACIFIC NW LAB)); Zhao, Rui (ASSOC WESTERN UNIVERSITY); Pasa Tolic, Ljiljana (BATTELLE (PACIFIC NW LAB)); Li, Lingjun (Illinois Univ Of-Urbana/Champa); Berger, Scott J.(ASSOC WESTERN UNIVERSITY); Harkewicz, Richard (BATTELLE (PACIFIC NW LAB)); Anderson, Gordon A.(BATTELLE (PACIFIC NW LAB)); Belov, Mikhail E.(BATTELLE (PACIFIC NW LAB)); Smith, Richard D.(BATTELLE (PACIFIC NW LAB))

    2000-12-01

    We report on the design and application of a high-efficiency multiple-capillary liquid chromatography (LC) system for high-throughput proteome analysis. The multiple-capillary LC system was operated at the pressure of 10,000 psi using commercial LC pumps to deliver the mobile phase and newly developed passive feedback valves to switch the mobile phase flow and introduce samples. The multiple-capillary LC system was composed of several serially connected dual-capillary column devices. The dual-capillary column approach was designed to eliminate the time delay for regeneration (or equilibrium) of the capillary column after its use under the mobile phase gradient condition (i.e. one capillary column was used in separation and the other was washed using mobile phase A). The serially connected dual-capillary columns and ESI sources were operated independently, and could be used for either''backup'' operation or with other mass spectrometer(s). This high-efficiency multiple-capillary LC system uses switching valves for all operations and is highly amenable to automation. The separations efficiency of dual-capillary column device, optimal capillary dimensions (column length and packed particle size), suitable mobile phases for electrospray, and the capillary re-generation were investigated. A high magnetic field (11.5 tesla) Fourier transform ion cyclotron resonance (FTICR) mass spectrometer was coupled on-line with this high-efficiency multiple-capillary LC system through an electrospray ionization source. The capillary LC provided a peak capacity of {approx}600, and the 2-D capillary LC-FTICR provided a combined resolving power of > 6 x 10 7 polypeptide isotopic distributions. For yeast cellular tryptic digests, > 100,000 polypeptides were typically detected, and {approx}1,000 proteins can be characterized in a single run.

  4. High-resolution continuum source atomic absorption spectrometry for the simultaneous or sequential monitoring of multiple lines. A critical review of current possibilities

    Resano, M.; Flórez, M.R.; García-Ruiz, E.

    2013-01-01

    This work examines the capabilities and limitations of commercially available high-resolution continuum source atomic absorption spectrometry instrumentation for multi-line monitoring, discussing in detail the possible strategies to develop multi-element methodologies that are truly simultaneous, or else sequential, but from the same sample aliquot. Moreover, the simultaneous monitoring of various atomic or molecular lines may bring other important analytical advantages, such as: i) expansion of the linear range by monitoring multiplets; ii) improvements in the limit of detection and in precision by summing the signals from different lines of the same element or molecule; iii) simple correction for matrix-effects by selecting a suitable internal standard; or iv) accurate mathematical correction of spectral overlaps by simultaneous monitoring of free lines of the interfering molecule or element. This work discusses how authors have made use of these strategies to develop analytical methodologies that permit the straightforward analysis of complex samples. - Highlights: • HR CS AAS potential for simultaneous multi-line monitoring is critically examined. • Strategies to develop simultaneous multi-element methods are discussed. • Other benefits of multi-line monitoring (e.g., use of an IS or LSBC) are highlighted. • Selected examples from the literature are discussed in detail

  5. A Method for Multiple Mycotoxin Analysis in Wines by Solid Phase Extraction and Multifunctional Cartridge Purification, and Ultra-High-Performance Liquid Chromatography Coupled to Tandem Mass Spectrometry

    Tamura, Masayoshi; Takahashi, Ayumi; Uyama, Atsuo; Mochizuki, Naoki

    2012-01-01

    An analytical method using two solid phase extractions and ultra-high-performance liquid chromatography coupled to tandem mass spectrometry (UHPLC-MS/MS) was developed for the identification and quantification of 14 mycotoxins (patulin, deoxynivalenol, aflatoxins B1, B2, G1, G2, M1, T-2 toxin, HT-2 toxin, zearalenone, fumonisins B1, B2, B3, and ochratoxin A) in domestic and imported wines. Mycotoxins were purified with an Oasis HLB cartridge, followed by a MultiSepTM #229 Ochra. As a result, sufficient removal of the pigments and highly polar matrices from the red wines was achieved. UHPLC conditions were optimized, and 14 mycotoxins were separated in a total of 13 min. Determinations performed using this method produced high correlation coefficients for the 14 mycotoxins (R > 0.990) and recovery rates ranging from 76 to 105% with good repeatability (relative standard deviation RSD < 12%). Twenty-seven samples of domestic and imported wines were analyzed using this method. Although ochratoxin A (OTA) and fumonisins (FMs) were detected in several samples, the FM levels were less than limits of quantification (LOQs) (1 μg/L), and even the largest of the OTA levels was below the EU regulatory level (2 μg/L). These results suggest that the health risk posed to consumers from the wines available in Japan is relatively low. PMID:22822458

  6. On the possibilities of high-resolution continuum source graphite furnace atomic absorption spectrometry for the simultaneous or sequential monitoring of multiple atomic lines

    Resano, M.; Rello, L.; Florez, M.; Belarra, M.A.

    2011-01-01

    This paper explores the potential of commercially available high-resolution continuum source graphite furnace atomic absorption spectrometry instrumentation for the simultaneous or sequential monitoring of various atomic lines, in an attempt to highlight the analytical advantages that can be derived from this strategy. In particular, it is demonstrated how i) the monitoring of multiplets may allow for the simple expansion of the linear range, as shown for the measurement of Ni using the triplet located in the vicinity of 234.6 nm; ii) the use of a suitable internal standard may permit improving the precision and help in correcting for matrix-effects, as proved for the monitoring of Ni in different biological samples; iii) direct and multi-element analysis of solid samples may be feasible on some occasions, either by monitoring various atomic lines that are sufficiently close (truly simultaneous monitoring, as demonstrated in the determination of Co, Fe and Ni in NIST 1566a Oyster tissue) or, alternatively, by opting for a selective and sequential atomization of the elements of interest during every single replicate. Determination of Cd and Ni in BCR 679 White cabbage is attempted using both approaches, which permits confirming that both methods can offer very similar and satisfactory results. However, it is important to stress that the second approach provides more flexibility, since analysis is no longer limited to those elements that show very close atomic lines (closer than 0.3 nm in the ultraviolet region) with a sensitivity ratio similar to the concentration ratio of the analytes in the samples investigated.

  7. Quantitative analysis of fragrance in selectable one dimensional or two dimensional gas chromatography-mass spectrometry with simultaneous detection of multiple detectors in single injection.

    Tan, Hui Peng; Wan, Tow Shi; Min, Christina Liew Shu; Osborne, Murray; Ng, Khim Hui

    2014-03-14

    A selectable one-dimensional ((1)D) or two-dimensional ((2)D) gas chromatography-mass spectrometry (GC-MS) system coupled with flame ionization detector (FID) and olfactory detection port (ODP) was employed in this study to analyze perfume oil and fragrance in shower gel. A split/splitless (SSL) injector and a programmable temperature vaporization (PTV) injector are connected via a 2-way splitter of capillary flow technology (CFT) in this selectable (1)D/(2)D GC-MS/FID/ODP system to facilitate liquid sample injections and thermal desorption (TD) for stir bar sorptive extraction (SBSE) technique, respectively. The dual-linked injectors set-up enable the use of two different injector ports (one at a time) in single sequence run without having to relocate the (1)D capillary column from one inlet to another. Target analytes were separated in (1)D GC-MS/FID/ODP and followed by further separation of co-elution mixture from (1)D in (2)D GC-MS/FID/ODP in single injection without any instrumental reconfiguration. A (1)D/(2)D quantitative analysis method was developed and validated for its repeatability - tR; calculated linear retention indices (LRI); response ratio in both MS and FID signal, limit of detection (LOD), limit of quantitation (LOQ), as well as linearity over a concentration range. The method was successfully applied in quantitative analysis of perfume solution at different concentration level (RSD≤0.01%, n=5) and shower gel spiked with perfume at different dosages (RSD≤0.04%, n=5) with good recovery (96-103% for SSL injection; 94-107% for stir bar sorptive extraction-thermal desorption (SBSE-TD). Copyright © 2014 Elsevier B.V. All rights reserved.

  8. Using systems thinking to identify workforce enablers for a whole systems approach to urgent and emergency care delivery: a multiple case study.

    Manley, Kim; Martin, Anne; Jackson, Carolyn; Wright, Toni

    2016-08-09

    Overcrowding in emergency departments is a global issue, which places pressure on the shrinking workforce and threatens the future of high quality, safe and effective care. Healthcare reforms aimed at tackling this crisis have focused primarily on structural changes, which alone do not deliver anticipated improvements in quality and performance. The purpose of this study was to identify workforce enablers for achieving whole systems urgent and emergency care delivery. A multiple case study design framed around systems thinking was conducted in South East England across one Trust consisting of five hospitals, one community healthcare trust and one ambulance trust. Data sources included 14 clinical settings where upstream or downstream pinch points are likely to occur including discharge planning and rapid response teams; ten regional stakeholder events (n = 102); a qualitative survey (n = 48); and a review of literature and analysis of policy documents including care pathways and protocols. The key workforce enablers for whole systems urgent and emergency care delivery identified were: clinical systems leadership, a single integrated career and competence framework and skilled facilitation of work based learning. In this study, participants agreed that whole systems urgent and emergency care allows for the design and implementation of care delivery models that meet complexity of population healthcare needs, reduce duplication and waste and improve healthcare outcomes and patients' experiences. For this to be achieved emphasis needs to be placed on holistic changes in structures, processes and patterns of the urgent and emergency care system. Often overlooked, patterns that drive the thinking and behavior in the workplace directly impact on staff recruitment and retention and the overall effectiveness of the organization. These also need to be attended to for transformational change to be achieved and sustained. Research to refine and validate a single

  9. Multiplicity evolution of identified particle charge-dependent correlations in Pb-Pb, p-Pb and pp collisions at the LHC with ALICE

    Pan, Jinjin; Alice Collaboration

    2017-09-01

    The charge pair creation and transport processes in heavy-ion collisions are investigated experimentally by measurements of charge-dependent correlations of identified particle pairs, related to the Balance Function. The produced pair separation in rapidity is expected to be larger for hadrons arising from quark-antiquark pair creation in the early stages of the collision than for hadrons emerging from the later hadronization stage. Correlations are reported for charged-pion pairs in Pb-Pb, p-Pb and pp collisions at √{sNN } = 2.76, 5.02 and 7 TeV, respectively; and for charged-kaon pairs in Pb-Pb collisions at √{sNN } = 2.76 TeV. The correlations are measured as a function of relative rapidity Δy and azimuthal angle Δϕ , and are dominated by a peak centered at Δy = Δϕ = 0. We observe that the peak widths in Δy and Δϕ are narrower in higher multiplicity events in Pb-Pb, p-Pb, and pp collisions, which is consistent with the effects of radial flow, as well as the two-wave quark production mechanism. We investigate the charge transport and system evolution further by studying the Δϕ width of the peak as a function of Δy. Funded by the US Department of Energy.

  10. Effect modification of air pollution on Urinary 8-Hydroxy-2'-Deoxyguanosine by genotypes: an application of the multiple testing procedure to identify significant SNP interactions

    Christiani David C

    2010-12-01

    Full Text Available Abstract Background Air pollution is associated with adverse human health, but mechanisms through which pollution exerts effects remain to be clarified. One suggested pathway is that pollution causes oxidative stress. If so, oxidative stress-related genotypes may modify the oxidative response defenses to pollution exposure. Methods We explored the potential pathway by examining whether an array of oxidative stress-related genes (twenty single nucleotide polymorphisms, SNPs in nine genes modified associations of pollutants (organic carbon (OC, ozone and sulfate with urinary 8-hydroxy-2-deoxygunosine (8-OHdG, a biomarker of oxidative stress among the 320 aging men. We used a Multiple Testing Procedure in R modified by our team to identify the significance of the candidate genes adjusting for a priori covariates. Results We found that glutathione S-tranferase P1 (GSTP1, rs1799811, M1 and catalase (rs2284367 and group-specific component (GC, rs2282679, rs1155563 significantly or marginally significantly modified effects of OC and/or sulfate with larger effects among those carrying the wild type of GSTP1, catalase, non-wild type of GC and the non-null of GSTM1. Conclusions Polymorphisms of oxidative stress-related genes modified effects of OC and/or sulfate on 8-OHdG, suggesting that effects of OC or sulfate on 8-OHdG and other endpoints may be through the oxidative stress pathway.

  11. Hormone-induced protection against mammary tumorigenesis is conserved in multiple rat strains and identifies a core gene expression signature induced by pregnancy.

    Blakely, Collin M; Stoddard, Alexander J; Belka, George K; Dugan, Katherine D; Notarfrancesco, Kathleen L; Moody, Susan E; D'Cruz, Celina M; Chodosh, Lewis A

    2006-06-15

    Women who have their first child early in life have a substantially lower lifetime risk of breast cancer. The mechanism for this is unknown. Similar to humans, rats exhibit parity-induced protection against mammary tumorigenesis. To explore the basis for this phenomenon, we identified persistent pregnancy-induced changes in mammary gene expression that are tightly associated with protection against tumorigenesis in multiple inbred rat strains. Four inbred rat strains that exhibit marked differences in their intrinsic susceptibilities to carcinogen-induced mammary tumorigenesis were each shown to display significant protection against methylnitrosourea-induced mammary tumorigenesis following treatment with pregnancy levels of estradiol and progesterone. Microarray expression profiling of parous and nulliparous mammary tissue from these four strains yielded a common 70-gene signature. Examination of the genes constituting this signature implicated alterations in transforming growth factor-beta signaling, the extracellular matrix, amphiregulin expression, and the growth hormone/insulin-like growth factor I axis in pregnancy-induced alterations in breast cancer risk. Notably, related molecular changes have been associated with decreased mammographic density, which itself is strongly associated with decreased breast cancer risk. Our findings show that hormone-induced protection against mammary tumorigenesis is widely conserved among divergent rat strains and define a gene expression signature that is tightly correlated with reduced mammary tumor susceptibility as a consequence of a normal developmental event. Given the conservation of this signature, these pathways may contribute to pregnancy-induced protection against breast cancer.

  12. Intra-event correlations and the statistical moments of the identified particle multiplicity distributions in the RHIC beam energy scan data collected by STAR

    Llope, W. J.; STAR Collaboration

    2013-10-01

    Specific products of the statistical moments of the multiplicity distributions of identified particles can be directly compared to susceptibility ratios obtained from lattice QCD calculations. They may also diverge for nuclear systems formed close to a possible QCD critical point due to the phenomenon of critical opalescence. Of particular interest are the moments products for net-protons, net-kaons, and net-charge, as these are considered proxies for conserved quantum numbers. The moments products have been measured by the STAR experiment for Au+Au collisions at seven beam energies ranging from 7.7 to 200 GeV. In this presentation, the experimental results are compared to data-based calculations in which the intra-event correlations of the numbers of positive and negative particles are broken by construction. The importance of intra-event correlations to the moments products values for net-protons, net-kaons, and net-charge can thus be evaluated. Work supported by the U.S. Dept of Energy under grant DE-PS02-09ER09.

  13. Experimental assessment of the importance of amino acid positions identified by an entropy-based correlation analysis of multiple-sequence alignments.

    Dietrich, Susanne; Borst, Nadine; Schlee, Sandra; Schneider, Daniel; Janda, Jan-Oliver; Sterner, Reinhard; Merkl, Rainer

    2012-07-17

    The analysis of a multiple-sequence alignment (MSA) with correlation methods identifies pairs of residue positions whose occupation with amino acids changes in a concerted manner. It is plausible to assume that positions that are part of many such correlation pairs are important for protein function or stability. We have used the algorithm H2r to identify positions k in the MSAs of the enzymes anthranilate phosphoribosyl transferase (AnPRT) and indole-3-glycerol phosphate synthase (IGPS) that show a high conn(k) value, i.e., a large number of significant correlations in which k is involved. The importance of the identified residues was experimentally validated by performing mutagenesis studies with sAnPRT and sIGPS from the archaeon Sulfolobus solfataricus. For sAnPRT, five H2r mutant proteins were generated by replacing nonconserved residues with alanine or the prevalent residue of the MSA. As a control, five residues with conn(k) values of zero were chosen randomly and replaced with alanine. The catalytic activities and conformational stabilities of the H2r and control mutant proteins were analyzed by steady-state enzyme kinetics and thermal unfolding studies. Compared to wild-type sAnPRT, the catalytic efficiencies (k(cat)/K(M)) were largely unaltered. In contrast, the apparent thermal unfolding temperature (T(M)(app)) was lowered in most proteins. Remarkably, the strongest observed destabilization (ΔT(M)(app) = 14 °C) was caused by the V284A exchange, which pertains to the position with the highest correlation signal [conn(k) = 11]. For sIGPS, six H2r mutant and four control proteins with alanine exchanges were generated and characterized. The k(cat)/K(M) values of four H2r mutant proteins were reduced between 13- and 120-fold, and their T(M)(app) values were decreased by up to 5 °C. For the sIGPS control proteins, the observed activity and stability decreases were much less severe. Our findings demonstrate that positions with high conn(k) values have an

  14. Matrix-assisted Laser Desorption Ionization-Time-of-Flight Mass Spectrometry (MALDI-TOF MS) as a Reliable Tool to Identify Species of Catalase-negative Gram-positive Cocci not Belonging to the Streptococcus Genus.

    Almuzara, Marisa; Barberis, Claudia; Velázquez, Viviana Rojas; Ramirez, Maria Soledad; Famiglietti, Angela; Vay, Carlos

    2016-01-01

    To evaluate the performance of matrix-assisted laser desorption ionization-time-of-flight mass spectrometry (MALDI-TOF MS) by using 190 Catalase-negative Gram-Positive Cocci (GPC) clinical isolates. All isolates were identified by conventional phenotypic tests following the proposed scheme by Ruoff and Christensen and MALDI-TOF MS (Bruker Daltonics, BD, Bremen, Germany). Two different extraction methods (direct transfer formic acid method on spot and ethanol formic acid extraction method) and different cut-offs for genus/specie level identification were used. The score cut-offs recommended by the manufacturer (≥ 2.000 for species-level, 1.700 to 1.999 for genus level and genus level, ≥ 1.700 for species-level and score genus or species. MALDI-TOF MS identification was considered correct when the result obtained from MS database agreed with the phenotypic identification result. When both methods gave discordant results, the 16S rDNA or sodA genes sequencing was considered as the gold standard identification method. The results obtained by MS concordant with genes sequencing, although discordant with conventional phenotyping, were considered correct. MS results discordant with 16S or sod A identification were considered incorrect. Using the score cut-offs recommended by the manufacturer, 97.37% and 81.05% were correctly identified to genus and species level, respectively. On the other hand, using lower cut-off scores for identification, 97.89% and 94.21% isolates were correctly identified to genus and species level respectively by MALDI-TOF MS and no significant differences between the results obtained with two extraction methods were obtained. The results obtained suggest that MALDI-TOF MS has the potential of being an accurate tool for Catalase-negative GPC identification even for those species with difficult diagnosis as Helcococcus , Abiotrophia , Granulicatella , among others. Nevertheless, expansion of the library, especially including more strains with

  15. NAViGaTing the micronome--using multiple microRNA prediction databases to identify signalling pathway-associated microRNAs.

    Elize A Shirdel

    2011-02-01

    Full Text Available MicroRNAs are a class of small RNAs known to regulate gene expression at the transcript level, the protein level, or both. Since microRNA binding is sequence-based but possibly structure-specific, work in this area has resulted in multiple databases storing predicted microRNA:target relationships computed using diverse algorithms. We integrate prediction databases, compare predictions to in vitro data, and use cross-database predictions to model the microRNA:transcript interactome--referred to as the micronome--to study microRNA involvement in well-known signalling pathways as well as associations with disease. We make this data freely available with a flexible user interface as our microRNA Data Integration Portal--mirDIP (http://ophid.utoronto.ca/mirDIP.mirDIP integrates prediction databases to elucidate accurate microRNA:target relationships. Using NAViGaTOR to produce interaction networks implicating microRNAs in literature-based, KEGG-based and Reactome-based pathways, we find these signalling pathway networks have significantly more microRNA involvement compared to chance (p<0.05, suggesting microRNAs co-target many genes in a given pathway. Further examination of the micronome shows two distinct classes of microRNAs; universe microRNAs, which are involved in many signalling pathways; and intra-pathway microRNAs, which target multiple genes within one signalling pathway. We find universe microRNAs to have more targets (p<0.0001, to be more studied (p<0.0002, and to have higher degree in the KEGG cancer pathway (p<0.0001, compared to intra-pathway microRNAs.Our pathway-based analysis of mirDIP data suggests microRNAs are involved in intra-pathway signalling. We identify two distinct classes of microRNAs, suggesting a hierarchical organization of microRNAs co-targeting genes both within and between pathways, and implying differential involvement of universe and intra-pathway microRNAs at the disease level.

  16. Systematic approach to optimize a pretreatment method for ultrasensitive liquid chromatography with tandem mass spectrometry analysis of multiple target compounds in biological samples.

    Togashi, Kazutaka; Mutaguchi, Kuninori; Komuro, Setsuko; Kataoka, Makoto; Yamazaki, Hiroshi; Yamashita, Shinji

    2016-08-01

    In current approaches for new drug development, highly sensitive and robust analytical methods for the determination of test compounds in biological samples are essential. These analytical methods should be optimized for every target compound. However, for biological samples that contain multiple compounds as new drug candidates obtained by cassette dosing tests, it would be preferable to develop a single method that allows the determination of all compounds at once. This study aims to establish a systematic approach that enables a selection of the most appropriate pretreatment method for multiple target compounds without the use of their chemical information. We investigated the retention times of 27 known compounds under different mobile phase conditions and determined the required pretreatment of human plasma samples using several solid-phase and liquid-liquid extractions. From the relationship between retention time and recovery in a principal component analysis, appropriate pretreatments were categorized into several types. Based on the category, we have optimized a pretreatment method for the identification of three calcium channel blockers in human plasma. Plasma concentrations of these drugs in a cassette-dose clinical study at microdose level were successfully determined with a lower limit of quantitation of 0.2 pg/mL for diltiazem, 1 pg/mL for nicardipine, and 2 pg/mL for nifedipine. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  17. Compensation of matrix effects in gas chromatography-mass spectrometry analysis of pesticides using a combination of matrix matching and multiple isotopically labeled internal standards.

    Tsuchiyama, Tomoyuki; Katsuhara, Miki; Nakajima, Masahiro

    2017-11-17

    In the multi-residue analysis of pesticides using GC-MS, the quantitative results are adversely affected by a phenomenon known as the matrix effect. Although the use of matrix-matched standards is considered to be one of the most practical solutions to this problem, complete removal of the matrix effect is difficult in complex food matrices owing to their inconsistency. As a result, residual matrix effects can introduce analytical errors. To compensate for residual matrix effects, we have developed a novel method that employs multiple isotopically labeled internal standards (ILIS). The matrix effects of ILIS and pesticides were evaluated in spiked matrix extracts of various agricultural commodities, and the obtained data were subjected to simple statistical analysis. Based on the similarities between the patterns of variation in the analytical response, a total of 32 isotopically labeled compounds were assigned to 338 pesticides as internal standards. It was found that by utilizing multiple ILIS, residual matrix effects could be effectively compensated. The developed method exhibited superior quantitative performance compared with the common single-internal-standard method. The proposed method is more feasible for regulatory purposes than that using only predetermined correction factors and is considered to be promising for practical applications. Copyright © 2017 Elsevier B.V. All rights reserved.

  18. An improved pseudotargeted metabolomics approach using multiple ion monitoring with time-staggered ion lists based on ultra-high performance liquid chromatography/quadrupole time-of-flight mass spectrometry

    Wang, Yang; Liu, Fang; Li, Peng; He, Chengwei; Wang, Ruibing; Su, Huanxing; Wan, Jian-Bo

    2016-01-01

    Pseudotargeted metabolomics is a novel strategy integrating the advantages of both untargeted and targeted methods. The conventional pseudotargeted metabolomics required two MS instruments, i.e., ultra-high performance liquid chromatography/quadrupole-time- of-flight mass spectrometry (UHPLC/Q-TOF MS) and UHPLC/triple quadrupole mass spectrometry (UHPLC/QQQ-MS), which makes method transformation inevitable. Furthermore, the picking of ion pairs from thousands of candidates and the swapping of the data between two instruments are the most labor-intensive steps, which greatly limit its application in metabolomic analysis. In the present study, we proposed an improved pseudotargeted metabolomics method that could be achieved on an UHPLC/Q-TOF/MS instrument operated in the multiple ion monitoring (MIM) mode with time-staggered ion lists (tsMIM). Full scan-based untargeted analysis was applied to extract the target ions. After peak alignment and ion fusion, a stepwise ion picking procedure was used to generate the ion lists for subsequent single MIM and tsMIM. The UHPLC/Q-TOF tsMIM MS-based pseudotargeted approach exhibited better repeatability and a wider linear range than the UHPLC/Q-TOF MS-based untargeted metabolomics method. Compared to the single MIM mode, the tsMIM significantly increased the coverage of the metabolites detected. The newly developed method was successfully applied to discover plasma biomarkers for alcohol-induced liver injury in mice, which indicated its practicability and great potential in future metabolomics studies. - Highlights: • An UHPLC/Q-TOF tsMIM MS-based pseudotargeted metabolomics was proposed. • Compared to full scan, the improved method exhibits better repeatability and a wider linear range. • The proposed method could achieve pseudotargeted analysis on one UHPLC/Q-TOF/MS instrument. • The developed method was successfully used to discover biomarkers for alcohol-induced liver injury.

  19. An improved pseudotargeted metabolomics approach using multiple ion monitoring with time-staggered ion lists based on ultra-high performance liquid chromatography/quadrupole time-of-flight mass spectrometry

    Wang, Yang; Liu, Fang; Li, Peng; He, Chengwei; Wang, Ruibing; Su, Huanxing; Wan, Jian-Bo, E-mail: jbwan@umac.mo

    2016-07-13

    Pseudotargeted metabolomics is a novel strategy integrating the advantages of both untargeted and targeted methods. The conventional pseudotargeted metabolomics required two MS instruments, i.e., ultra-high performance liquid chromatography/quadrupole-time- of-flight mass spectrometry (UHPLC/Q-TOF MS) and UHPLC/triple quadrupole mass spectrometry (UHPLC/QQQ-MS), which makes method transformation inevitable. Furthermore, the picking of ion pairs from thousands of candidates and the swapping of the data between two instruments are the most labor-intensive steps, which greatly limit its application in metabolomic analysis. In the present study, we proposed an improved pseudotargeted metabolomics method that could be achieved on an UHPLC/Q-TOF/MS instrument operated in the multiple ion monitoring (MIM) mode with time-staggered ion lists (tsMIM). Full scan-based untargeted analysis was applied to extract the target ions. After peak alignment and ion fusion, a stepwise ion picking procedure was used to generate the ion lists for subsequent single MIM and tsMIM. The UHPLC/Q-TOF tsMIM MS-based pseudotargeted approach exhibited better repeatability and a wider linear range than the UHPLC/Q-TOF MS-based untargeted metabolomics method. Compared to the single MIM mode, the tsMIM significantly increased the coverage of the metabolites detected. The newly developed method was successfully applied to discover plasma biomarkers for alcohol-induced liver injury in mice, which indicated its practicability and great potential in future metabolomics studies. - Highlights: • An UHPLC/Q-TOF tsMIM MS-based pseudotargeted metabolomics was proposed. • Compared to full scan, the improved method exhibits better repeatability and a wider linear range. • The proposed method could achieve pseudotargeted analysis on one UHPLC/Q-TOF/MS instrument. • The developed method was successfully used to discover biomarkers for alcohol-induced liver injury.

  20. An improved pseudotargeted metabolomics approach using multiple ion monitoring with time-staggered ion lists based on ultra-high performance liquid chromatography/quadrupole time-of-flight mass spectrometry.

    Wang, Yang; Liu, Fang; Li, Peng; He, Chengwei; Wang, Ruibing; Su, Huanxing; Wan, Jian-Bo

    2016-07-13

    Pseudotargeted metabolomics is a novel strategy integrating the advantages of both untargeted and targeted methods. The conventional pseudotargeted metabolomics required two MS instruments, i.e., ultra-high performance liquid chromatography/quadrupole-time- of-flight mass spectrometry (UHPLC/Q-TOF MS) and UHPLC/triple quadrupole mass spectrometry (UHPLC/QQQ-MS), which makes method transformation inevitable. Furthermore, the picking of ion pairs from thousands of candidates and the swapping of the data between two instruments are the most labor-intensive steps, which greatly limit its application in metabolomic analysis. In the present study, we proposed an improved pseudotargeted metabolomics method that could be achieved on an UHPLC/Q-TOF/MS instrument operated in the multiple ion monitoring (MIM) mode with time-staggered ion lists (tsMIM). Full scan-based untargeted analysis was applied to extract the target ions. After peak alignment and ion fusion, a stepwise ion picking procedure was used to generate the ion lists for subsequent single MIM and tsMIM. The UHPLC/Q-TOF tsMIM MS-based pseudotargeted approach exhibited better repeatability and a wider linear range than the UHPLC/Q-TOF MS-based untargeted metabolomics method. Compared to the single MIM mode, the tsMIM significantly increased the coverage of the metabolites detected. The newly developed method was successfully applied to discover plasma biomarkers for alcohol-induced liver injury in mice, which indicated its practicability and great potential in future metabolomics studies. Copyright © 2016 Elsevier B.V. All rights reserved.

  1. Stable isotope ratiometer-multiple ion detector (SIRMID) unit for quantitative and qualitative stable isotope studies by gas chromatography-mass spectrometry

    Klein, P.D.; Haumann, J.R.; Hachey, D.L.

    1975-01-01

    A stable isotope ratiometer-multiple ion detector (SIRMID) unit which can drive existing gas chromatograph-quadrupole or magnetic sector mass spectrometers to monitor up to six ions in turn is described. Each of the three pairs of ions can be selected for quantitation; thus three different or successive components can be analyzed in a single GC run. A background subtraction option permits the ion intensity in the absence of sample to be subtracted automatically during sample measurement. Displays of accumulated counts and isotope ratio are updated twice per second during the measurement and can be printed out at its conclusion. All six ions can be monitored in the analog mode by parallel outputs to a multipen recorder. Experience gained in the construction of this prototype indicates that SIRMID units could be commercially available for $10K, or about 1 / 3 rd to 1 / 6 th of the cost of even an inexpensive computer system. (U.S.)

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

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

    2016-02-11

    Multiple reaction monitoring (MRM) is a universal approach for quantitative analysis because of its high specificity and sensitivity. Nevertheless, optimization of MRM parameters remains as a time and labor-intensive task particularly in multiplexed quantitative analysis of small molecules in complex mixtures. In this study, we have developed an approach named Stepped MS(All) Relied Transition (SMART) to predict the optimal MRM parameters of small molecules. SMART requires firstly a rapid and high-throughput analysis of samples using a Stepped MS(All) technique (sMS(All)) on a Q-TOF, which consists of serial MS(All) events acquired from low CE to gradually stepped-up CE values in a cycle. The optimal CE values can then be determined by comparing the extracted ion chromatograms for the ion pairs of interest among serial scans. The SMART-predicted parameters were found to agree well with the parameters optimized on a triple quadrupole from the same vendor using a mixture of standards. The parameters optimized on a triple quadrupole from a different vendor was also employed for comparison, and found to be linearly correlated with the SMART-predicted parameters, suggesting the potential applications of the SMART approach among different instrumental platforms. This approach was further validated by applying to simultaneous quantification of 31 herbal components in the plasma of rats treated with a herbal prescription. Because the sMS(All) acquisition can be accomplished in a single run for multiple components independent of standards, the SMART approach are expected to find its wide application in the multiplexed quantitative analysis of complex mixtures. Copyright © 2015 Elsevier B.V. All rights reserved.

  3. Beta spectrometry

    Dryak, P.; Zderadicka, J.; Plch, J.; Kokta, L.; Novotna, P.

    1977-01-01

    For the purpose of beta spectrometry, a semiconductor spectrometer with one Si(Li) detector cooled with liquid nitrogen was designed. Geometrical detection efficiency is about 10% 4 sr. The achieved resolution for 624 keV conversion electrons of sup(137m)Ba is 2.6 keV (FWHM). A program was written in the FORTRAN language for the correction of the deformation of the measured spectra by backscattering in the analysis of continuous beta spectra. The method permits the determination of the maximum energy of the beta spectrum with an accuracy of +-5 keV. (author)

  4. Mass spectrometry-assisted protease substrate screening

    Schlüter, Hartmut; Rykl, Jana; Thiemann, Joachim

    2007-01-01

    -phase chromatography they are analyzed by tandem mass spectrometry and the substrates identified by database searching. The proof of principle in this study is demonstrated by incubating immobilized human plasma proteins with thrombin and by identifying by tandem mass spectrometry the fibrinopeptides, released...

  5. Spectrometry techniques for radioactivity measurements

    Anilkumar, S.

    2016-01-01

    The energy of the radiation emission following the nuclear decay is unique and the characteristic of the radio nuclide which undergoes decay. Thus measurement of the energy of the radiation offers a method of identifying the radio nuclides. The prime requirement of the energy measurement is a suitable detector which shows response proportional to the energy of the radiation rather than the presence of the radiation. The response from such detectors are suitably processed and distributed with respect to the signal strength which is proportional to incident energy. This distribution is normally referred as energy spectrum and is recorded in the multichannel analyser. The measurement of energy and intensity of radiation from the spectrum is called radiation spectrometry. Thus the radiation spectrometry allows the identification and quantification of radioactive isotopes in variety of matrices. The radiation spectrometry has now become a popular radioanalytical technique in wide area of nuclear fuel cycle programs. The popular spectrometry techniques commonly used for the radioactivity measurement and analysis are Alpha spectrometry, Gamma ray spectrometry and Beta spectrometry

  6. Imaging mass spectrometry statistical analysis.

    Jones, Emrys A; Deininger, Sören-Oliver; Hogendoorn, Pancras C W; Deelder, André M; McDonnell, Liam A

    2012-08-30

    Imaging mass spectrometry is increasingly used to identify new candidate biomarkers. This clinical application of imaging mass spectrometry is highly multidisciplinary: expertise in mass spectrometry is necessary to acquire high quality data, histology is required to accurately label the origin of each pixel's mass spectrum, disease biology is necessary to understand the potential meaning of the imaging mass spectrometry results, and statistics to assess the confidence of any findings. Imaging mass spectrometry data analysis is further complicated because of the unique nature of the data (within the mass spectrometry field); several of the assumptions implicit in the analysis of LC-MS/profiling datasets are not applicable to imaging. The very large size of imaging datasets and the reporting of many data analysis routines, combined with inadequate training and accessible reviews, have exacerbated this problem. In this paper we provide an accessible review of the nature of imaging data and the different strategies by which the data may be analyzed. Particular attention is paid to the assumptions of the data analysis routines to ensure that the reader is apprised of their correct usage in imaging mass spectrometry research. Copyright © 2012 Elsevier B.V. All rights reserved.

  7. Meta-genome-wide association studies identify a locus on chromosome 1 and multiple variants in the MHC region for serum C-peptide in type 1 diabetes.

    Roshandel, Delnaz; Gubitosi-Klug, Rose; Bull, Shelley B; Canty, Angelo J; Pezzolesi, Marcus G; King, George L; Keenan, Hillary A; Snell-Bergeon, Janet K; Maahs, David M; Klein, Ronald; Klein, Barbara E K; Orchard, Trevor J; Costacou, Tina; Weedon, Michael N; Oram, Richard A; Paterson, Andrew D

    2018-05-01

    The aim of this study was to identify genetic variants associated with beta cell function in type 1 diabetes, as measured by serum C-peptide levels, through meta-genome-wide association studies (meta-GWAS). We performed a meta-GWAS to combine the results from five studies in type 1 diabetes with cross-sectionally measured stimulated, fasting or random C-peptide levels, including 3479 European participants. The p values across studies were combined, taking into account sample size and direction of effect. We also performed separate meta-GWAS for stimulated (n = 1303), fasting (n = 2019) and random (n = 1497) C-peptide levels. In the meta-GWAS for stimulated/fasting/random C-peptide levels, a SNP on chromosome 1, rs559047 (Chr1:238753916, T>A, minor allele frequency [MAF] 0.24-0.26), was associated with C-peptide (p = 4.13 × 10 -8 ), meeting the genome-wide significance threshold (p C>T, MAF 0.07-0.10, p = 8.43 × 10 -8 ). In the stimulated C-peptide meta-GWAS, rs61211515 (Chr6:30100975, T/-, MAF 0.17-0.19) in the MHC region was associated with stimulated C-peptide (β [SE] = - 0.39 [0.07], p = 9.72 × 10 -8 ). rs61211515 was also associated with the rate of stimulated C-peptide decline over time in a subset of individuals (n = 258) with annual repeated measures for up to 6 years (p = 0.02). In the meta-GWAS of random C-peptide, another MHC region, SNP rs3135002 (Chr6:32668439, C>A, MAF 0.02-0.06), was associated with C-peptide (p = 3.49 × 10 -8 ). Conditional analyses suggested that the three identified variants in the MHC region were independent of each other. rs9260151 and rs3135002 have been associated with type 1 diabetes, whereas rs559047 and rs61211515 have not been associated with a risk of developing type 1 diabetes. We identified a locus on chromosome 1 and multiple variants in the MHC region, at least some of which were distinct from type 1 diabetes risk loci, that were associated with C

  8. Identification of chemical components in Baidianling Capsule based on gas chromatography-mass spectrometry and high-performance liquid chromatography combined with Fourier transform ion cyclotron resonance mass spectrometry.

    Wu, Wenying; Chen, Yu; Wang, Binjie; Sun, Xiaoyang; Guo, Ping; Chen, Xiaohui

    2017-08-01

    Baidianling Capsule, which is made from 16 Chinese herbs, has been widely used for treating vitiligo clinically. In this study, the sensitive and rapid method has been developed for the analysis of chemical components in Baidianling Capsule by gas chromatography-mass spectrometry in combination with retention indices and high-performance liquid chromatography combined with Fourier transform ion cyclotron resonance mass spectrometry. Firstly, a total of 110 potential volatile compounds obtained from different extraction procedures including alkanes, alkenes, alkynes, ketones, ethers, aldehydes, alcohols, phenols, organic acids, esters, furans, pyrrole, acid amides, heterocycles, and oxides were detected from Baidianling Capsule by gas chromatography-mass spectrometry, of which 75 were identified by mass spectrometry in combination with the retention index. Then, a total of 124 components were tentatively identified by high-performance liquid chromatography combined with Fourier transform ion cyclotron resonance mass spectrometry. Fifteen constituents from Baidianling Capsule were accurately identified by comparing the retention times with those of reference compounds, others were identified by comparing the retention times and mass spectrometry data, as well as retrieving the reference literature. This study provides a practical strategy for rapidly screening and identifying the multiple constituents of a complex traditional Chinese medicine. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  9. Analysis of multiple vitamin D metabolites by ultra-performance supercritical fluid chromatography-tandem mass spectrometry (UPSFC-MS/MS).

    Jenkinson, Carl; Taylor, Angela; Storbeck, Karl-Heinz; Hewison, Martin

    2018-06-15

    In recent years, increased interest in the human health benefits of vitamin D has led to demand for improved analysis of patient vitamin D 'status'. Studies to date have focused primarily on a single vitamin D metabolite, 25-hydroxyvitamin D, despite the existence of a broad range of vitamin D metabolites, referred to as the vitamin D metabolome. This study reports on the development of a rapid UPSFC-MS/MS method for the analysis of nine vitamin D metabolites in human serum. Optimum separation was obtained with a Lux-Cellulose chiral column. We observed an orthogonal elution order when compared with ultra-high performance liquid chromatography (UHPLC). The order of elution was reversed based on hydroxyl- group number, however elution order did not differ between isomeric changes in hydroxyl- group position or epimers. Although UPSFC yielded superior resolution and selectivity over previously developed UHPLC-MS/MS methods, improvements in sensitivity could not be achieved owing to the lower injection volume required for UPSFC relative to UHPLC. Method validation was performed on the developed UPSFC-MS/MS method and found to be within acceptable limits. Applying the method to the analysis of human serum samples showed a significant correlation with serum concentrations of metabolites measured by UHPLC-MS/MS (25OHD3 r = 0.997, P=<0.001, and 3-epi-25OHD3 r = 0.996, P ≤0.001). These data indicate that UPSFC provides an efficient analytical platform for rapid analysis of multiple vitamin D metabolites from serum. Crown Copyright © 2018. Published by Elsevier B.V. All rights reserved.

  10. Inflammatory Response and Barrier Dysfunction by Different e-Cigarette Flavoring Chemicals Identified by Gas Chromatography-Mass Spectrometry in e-Liquids and e-Vapors on Human Lung Epithelial Cells and Fibroblasts.

    Gerloff, Janice; Sundar, Isaac K; Freter, Robert; Sekera, Emily R; Friedman, Alan E; Robinson, Risa; Pagano, Todd; Rahman, Irfan

    2017-03-01

    Recent studies suggest that electronic cigarette (e-cig) flavors can be harmful to lung tissue by imposing oxidative stress and inflammatory responses. The potential inflammatory response by lung epithelial cells and fibroblasts exposed to e-cig flavoring chemicals in addition to other risk-anticipated flavor enhancers inhaled by e-cig users is not known. The goal of this study was to evaluate the release of the proinflammatory cytokine (interleukin-8 [IL-8]) and epithelial barrier function in response to different e-cig flavoring chemicals identified in various e-cig e-liquid flavorings and vapors by chemical characterization using gas chromatography-mass spectrometry analysis. Flavorings, such as acetoin (butter), diacetyl, pentanedione, maltol (malt), ortho-vanillin (vanilla), coumarin, and cinnamaldehyde in comparison with tumor necrosis factor alpha (TNFα), were used in this study. Human bronchial epithelial cells (Beas2B), human mucoepidermoid carcinoma epithelial cells (H292), and human lung fibroblasts (HFL-1) were treated with each flavoring chemical for 24 hours. The cells and conditioned media were then collected and analyzed for toxicity (viability %), lung epithelial barrier function, and proinflammatory cytokine IL-8 release. Cell viability was not significantly affected by any of the flavoring chemicals tested at a concentration of 10 μM to 1 mM. Acetoin and diacetyl treatment induced IL-8 release in Beas2B cells. Acetoin- and pentanedione-treated HFL-1 cells produced a differential, but significant response for IL-8 release compared to controls and TNFα. Flavorings, such as ortho-vanillin and maltol, induced IL-8 release in Beas2B cells, but not in H292 cells. Of all the flavoring chemicals tested, acetoin and maltol were more potent inducers of IL-8 release than TNFα in Beas2B and HFL-1 cells. Flavoring chemicals rapidly impaired epithelial barrier function in human bronchial epithelial cells (16-HBE) as measured by electric cell surface

  11. Coincidence gamma-ray spectrometry

    Markovic, Nikola; Roos, Per; Nielsen, Sven Poul

    2017-01-01

    Gamma-ray spectrometry with high-purity germanium (HPGe) detectors is often the technique of choice in an environmental radioactivity laboratory. When measuring environmental samples associated activities are usually low so an important parameter that describes the performance of the spectrometer...... for a nuclide of interest is the minimum detectable activity (MDA). There are many ways for lowering the MDAs in gamma spectrometry. Recently, developments of fast and compact digital acquisition systems have led to growing number of multiple HPGe detector spectrometers. In these applications all detected...

  12. Qualitative and quantitative analysis of heparin and low molecular weight heparins using size exclusion chromatography with multiple angle laser scattering/refractive index and inductively coupled plasma/mass spectrometry detectors.

    Ouyang, Yilan; Zeng, Yangyang; Yi, Lin; Tang, Hong; Li, Duxin; Linhardt, Robert J; Zhang, Zhenqing

    2017-11-03

    Heparin, a highly sulfated glycosaminoglycan, has been used as a clinical anticoagulant over 80 years. Low molecular weight heparins (LMWHs), heparins partially depolymerized using different processes, are widely used as clinical anticoagulants. Qualitative molecular weight (MW) and quantitative mass content analysis are two important factors that contribute to LMWH quality control. Size exclusion chromatography (SEC), relying on multiple angle laser scattering (MALS)/refractive index (RI) detectors, has been developed for accurate analysis of heparin MW in the absence of standards. However, the cations, which ion-pair with the anionic polysaccharide chains of heparin and LMWHs, had not been considered in previous reports. In this study, SEC with MALS/RI and inductively coupled plasma/mass spectrometry detectors were used in a comprehensive analytical approach taking both anionic polysaccharide and ion-paired cations heparin products. This approach was also applied to quantitative analysis of heparin and LMWHs. Full profiles of MWs and mass recoveries for three commercial heparin/LMWH products, heparin sodium, enoxaparin sodium and nadroparin calcium, were obtained and all showed higher MWs than previously reported. This important improvement more precisely characterized the MW properties of heparin/LMWHs and potentially many other anionic polysaccharides. Copyright © 2017 Elsevier B.V. All rights reserved.

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

    Chen, Xiaocheng; Cao, Gang; Jiang, Jianping

    2014-01-01

    Objective: The present study examined the pharmacokinetic profiles of two iridoid glycosides named morroniside and loganin in rat plasma after oral administration of crude and processed Cornus officinals. Materials and Methods: A rapid, selective and specific high-performance liquid chromatography/electrospray ionization tandem mass spectrometry with multiple reactions monitoring mode was developed to simultaneously investigate the pharmacokinetic profiles of morroniside and loganin in rat plasma after oral administration of crude C. officinals and its jiuzhipin. Results: The morroniside and loganin in crude and processed C. officinals could be simultaneously determined within 7.4 min. Linear calibration curves were obtained over the concentration ranges of 45.45-4800 ng/mL for all the analytes. The intra-and inter-day precisions relative standard deviation was lesser than 2.84% and 4.12%, respectively. Conclusion: The pharmacokinetic parameters of two iridoid glucosides were also compared systematically between crude and processed C. officinals. This paper provides the theoretical proofs for further explaining the processing mechanism of Traditional Chinese Medicines. PMID:24914290

  14. Identification and analysis of chemical constituents and rat serum metabolites in Suan-Zao-Ren granule using ultra high performance liquid chromatography quadrupole time-of-flight mass spectrometry combined with multiple data processing approaches.

    Du, Yiyang; He, Bosai; Li, Qing; He, Jiao; Wang, Di; Bi, Kaishun

    2017-07-01

    Suan-Zao-Ren granule is widely used to treat insomnia in China. However, because of the complexity and diversity of the chemical compositions in traditional Chinese medicine formula, the comprehensive analysis of constituents in vitro and in vivo is rather difficult. In our study, an ultra high performance liquid chromatography with quadrupole time-of-flight mass spectrometry and the PeakView® software, which uses multiple data processing approaches including product ion filter, neutral loss filter, and mass defect filter, method was developed to characterize the ingredients and rat serum metabolites in Suan-Zao-Ren granule. A total of 101 constituents were detected in vitro. Under the same analysis conditions, 68 constituents were characterized in rat serum, including 35 prototype components and 33 metabolites. The metabolic pathways of main components were also illustrated. Among them, the metabolic pathways of timosaponin AI were firstly revealed. The bioactive compounds mainly underwent the phase I metabolic pathways including hydroxylation, oxidation, hydrolysis, and phase II metabolic pathways including sulfate conjugation, glucuronide conjugation, cysteine conjugation, acetycysteine conjugation, and glutathione conjugation. In conclusion, our results showed that this analysis approach was extremely useful for the in-depth pharmacological research of Suan-Zao-Ren granule and provided a chemical basis for its rational. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  15. New trends in nuclear spectrometry

    Westmeier, W.; Siemon, K.

    2013-01-01

    An overview on the status and function of current spectrometry hardware, of detectors having energy-dispersive (spectrometric) properties as well as of the latest developments in quantitative spectrometry software is presented. Making extensive use of modern computing power, new strategies in high-precision spectrum analysis have been developed which enhance the quality of results and also open new fields of spectrometric applications. Three principles have been newly introduced to spectrum analysis software: -use no approximations in modelling (Physics, no numerology) -apply all available models to find a solution (Fuzzy Logic) -repeat complete analyses for iterative improvement (Learn from results). -- Highlights: ► We present an overview of MCA hardware and detectors for nuclear spectrometry. ► Physics-oriented descriptions, Fuzzy Logic and multiple repetitive analyses lead to improved results in spectrum analysis. ► New strategies allow the successful deconvolution of spectra that could not be analysed before

  16. Multiplicity dependence of identified hadron production in pp collisions at √s = 7 TeV in the ALICE at LHC

    Nayak, Kishora

    2016-01-01

    Recent measurements in proton-lead (p-Pb) and high-multiplicity proton-proton (pp) collisions show some collective features that are similar to those observed in Pb-Pb collisions. We report the production of charged light flavour, strange and multi-strange hadrons (π; K; p; Λ; Ξ; Ω) at mid rapidity as a function of event multiplicity in pp collisions at √s = 7 TeV using the ALICE detectors. In the p_T -differential baryon to meson ratios (p/π; Λ/K"0_s), an enhancement of baryon production at intermediate p_T is observed in high-multiplicity pp collisions. This behavior is qualitatively similar to earlier measurements performed in p-Pb and Pb-Pb collisions as a function of event activity. The production rate of strange and multi-strange hadrons relative to pions exhibits a significant increase with multiplicity in the smaller colliding systems of pp and p-Pb, pointing to similar mechanisms at play in pp and p-Pb collisions. The results are also compared with QCD inspired model calculations. (author)

  17. GWAS of 972 autologous stem cell recipients with multiple myeloma identifies 11 genetic variants associated with chemotherapy-induced oral mucositis

    Coleman, Elizabeth Ann; Lee, Jeannette Y; Erickson, Stephen W

    2015-01-01

    PURPOSE: High-dose chemotherapy and autologous stem cell transplant (ASCT) to treat multiple myeloma (MM) and other cancers carries the risk of oral mucositis (OM) with sequelae including impaired nutritional and fluid intake, pain, and infectious complications. As a result of these problems, can...

  18. Mass Spectrometry Imaging, an Emerging Technology in Neuropsychopharmacology

    Shariatgorji, Mohammadreza; Svenningsson, Per; Andrén, Per E

    2014-01-01

    Mass spectrometry imaging is a powerful tool for directly determining the distribution of proteins, peptides, lipids, neurotransmitters, metabolites and drugs in neural tissue sections in situ. Molecule-specific imaging can be achieved using various ionization techniques that are suited to different applications but which all yield data with high mass accuracies and spatial resolutions. The ability to simultaneously obtain images showing the distributions of chemical species ranging from metal ions to macromolecules makes it possible to explore the chemical organization of a sample and to correlate the results obtained with specific anatomical features. The imaging of biomolecules has provided new insights into multiple neurological diseases, including Parkinson's and Alzheimer's disease. Mass spectrometry imaging can also be used in conjunction with other imaging techniques in order to identify correlations between changes in the distribution of important chemical species and other changes in the properties of the tissue. Here we review the applications of mass spectrometry imaging in neuroscience research and discuss its potential. The results presented demonstrate that mass spectrometry imaging is a useful experimental method with diverse applications in neuroscience. PMID:23966069

  19. Mass spectrometry imaging, an emerging technology in neuropsychopharmacology.

    Shariatgorji, Mohammadreza; Svenningsson, Per; Andrén, Per E

    2014-01-01

    Mass spectrometry imaging is a powerful tool for directly determining the distribution of proteins, peptides, lipids, neurotransmitters, metabolites and drugs in neural tissue sections in situ. Molecule-specific imaging can be achieved using various ionization techniques that are suited to different applications but which all yield data with high mass accuracies and spatial resolutions. The ability to simultaneously obtain images showing the distributions of chemical species ranging from metal ions to macromolecules makes it possible to explore the chemical organization of a sample and to correlate the results obtained with specific anatomical features. The imaging of biomolecules has provided new insights into multiple neurological diseases, including Parkinson's and Alzheimer's disease. Mass spectrometry imaging can also be used in conjunction with other imaging techniques in order to identify correlations between changes in the distribution of important chemical species and other changes in the properties of the tissue. Here we review the applications of mass spectrometry imaging in neuroscience research and discuss its potential. The results presented demonstrate that mass spectrometry imaging is a useful experimental method with diverse applications in neuroscience.

  20. Analysis of the genetic phylogeny of multifocal prostate cancer identifies multiple independent clonal expansions in neoplastic and morphologically normal prostate tissue.

    Cooper, Colin S; Eeles, Rosalind; Wedge, David C; Van Loo, Peter; Gundem, Gunes; Alexandrov, Ludmil B; Kremeyer, Barbara; Butler, Adam; Lynch, Andrew G; Camacho, Niedzica; Massie, Charlie E; Kay, Jonathan; Luxton, Hayley J; Edwards, Sandra; Kote-Jarai, ZSofia; Dennis, Nening; Merson, Sue; Leongamornlert, Daniel; Zamora, Jorge; Corbishley, Cathy; Thomas, Sarah; Nik-Zainal, Serena; O'Meara, Sarah; Matthews, Lucy; Clark, Jeremy; Hurst, Rachel; Mithen, Richard; Bristow, Robert G; Boutros, Paul C; Fraser, Michael; Cooke, Susanna; Raine, Keiran; Jones, David; Menzies, Andrew; Stebbings, Lucy; Hinton, Jon; Teague, Jon; McLaren, Stuart; Mudie, Laura; Hardy, Claire; Anderson, Elizabeth; Joseph, Olivia; Goody, Victoria; Robinson, Ben; Maddison, Mark; Gamble, Stephen; Greenman, Christopher; Berney, Dan; Hazell, Steven; Livni, Naomi; Fisher, Cyril; Ogden, Christopher; Kumar, Pardeep; Thompson, Alan; Woodhouse, Christopher; Nicol, David; Mayer, Erik; Dudderidge, Tim; Shah, Nimish C; Gnanapragasam, Vincent; Voet, Thierry; Campbell, Peter; Futreal, Andrew; Easton, Douglas; Warren, Anne Y; Foster, Christopher S; Stratton, Michael R; Whitaker, Hayley C; McDermott, Ultan; Brewer, Daniel S; Neal, David E

    2015-04-01

    Genome-wide DNA sequencing was used to decrypt the phylogeny of multiple samples from distinct areas of cancer and morphologically normal tissue taken from the prostates of three men. Mutations were present at high levels in morphologically normal tissue distant from the cancer, reflecting clonal expansions, and the underlying mutational processes at work in morphologically normal tissue were also at work in cancer. Our observations demonstrate the existence of ongoing abnormal mutational processes, consistent with field effects, underlying carcinogenesis. This mechanism gives rise to extensive branching evolution and cancer clone mixing, as exemplified by the coexistence of multiple cancer lineages harboring distinct ERG fusions within a single cancer nodule. Subsets of mutations were shared either by morphologically normal and malignant tissues or between different ERG lineages, indicating earlier or separate clonal cell expansions. Our observations inform on the origin of multifocal disease and have implications for prostate cancer therapy in individual cases.

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

    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...

  2. High-throughput ultra high performance liquid chromatography combined with mass spectrometry approach for the rapid analysis and characterization of multiple constituents of the fruit of Acanthopanax senticosus (Rupr. et Maxim.) Harms.

    Han, Yue; Zhang, Aihua; Sun, Hui; Zhang, Yingzhi; Meng, Xiangcai; Yan, Guangli; Liu, Liang; Wang, Xijun

    2017-05-01

    Acanthopanax senticosus (Rupr. et Maxim.) Harms, a traditional Chinese medicine, has been widely used to improve the function of skeleton, heart, spleen and kidney. This fruit is rich in nutrients, but the chemical constituents of Acanthopanax senticosus fruit are still unclear. A rapid method based on ultra high performance liquid chromatography with time-of-flight mass spectrometry was developed for the compound analysis of Acanthopanax senticosus fruit in vitro and in vivo. In this study, the Acanthopanax senticosus fruit could significantly increase the weight of immune organs, promote the proliferation of lymphatic T cells, regulate the lymphatic B cell function, and decrease the ability of natural killer cells. A total of 104 compounds of Acanthopanax senticosus fruit including lignans, flavones, triterpenoidsaponins, phenolic acids, and other constituents were identified. Among them, seven chemical compounds were reported for the first time in the Acanthopanax senticosus fruit. Compared with the serum sample of blank and dosed samples, 24 prototype compositions were characterized. The results of our experiment could be helpful to understand the complex compounds of Acanthopanax senticosus fruit in vitro and in vivo for further pharmacological activity studies. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  3. Simultaneous Qualitative and Quantitative Analysis of Multiple Chemical Constituents in YiQiFuMai Injection by Ultra-Fast Liquid Chromatography Coupled with Ion Trap Time-of-Flight Mass Spectrometry

    Chunhua Liu

    2016-05-01

    Full Text Available YiQiFuMai injection (YQFM is a modern lyophilized powder preparation derived from the traditional Chinese medicine Sheng-mai san (SMS used for treating cardiovascular diseases, such as chronic heart failure. However, its chemical composition has not been fully elucidated, particularly for the preparation derived from Ophiopogon japonicus. This study aimed to establish a systematic and reliable method to quickly and simultaneously analyze the chemical constituents in YQFM by ultra-fast liquid chromatography coupled with ion trap time-of-flight mass spectrometry (UFLC-IT-TOF/MS. Sixty-five compounds in YQFM were tentatively identified by comparison with reference substances or literature data. Furthermore, twenty-one compounds, including three ophiopogonins, fifteen ginsenosides and three lignans were quantified by UFLC-IT-TOF/MS. Notably, this is the first determination of steroidal saponins from O. japonicus in YQFM. The relative standard deviations (RSDs of intra- and inter-day precision, reproducibility and stability were <4.9% and all analytes showed good linearity (R2 ≥ 0.9952 and acceptable recovery of 91.8%–104.2% (RSD ≤ 5.4%, indicating that the methods were reliable. These methods were successfully applied to quantitative analysis of ten batches of YQFM. The developed approach can provide useful and comprehensive information for quality control, further mechanistic studies in vivo and clinical application of YQFM.

  4. The Impact of College Education on Geographic Mobility: Identifying Education Using Multiple Components of Vietnam Draft Risk. NBER Working Paper No. 16463

    Malamud, Ofer; Wozniak, Abigail K.

    2010-01-01

    We examine whether higher education is a causal determinant of geographic mobility using variation in college attainment induced by draft-avoidance behavior during the Vietnam War. We use national and state-level induction risk to identify both educational attainment and veteran status among cohorts of affected men observed in the 1980 Census. Our…

  5. Robust Selection Algorithm (RSA) for Multi-Omic Biomarker Discovery; Integration with Functional Network Analysis to Identify miRNA Regulated Pathways in Multiple Cancers.

    Sehgal, Vasudha; Seviour, Elena G; Moss, Tyler J; Mills, Gordon B; Azencott, Robert; Ram, Prahlad T

    2015-01-01

    MicroRNAs (miRNAs) play a crucial role in the maintenance of cellular homeostasis by regulating the expression of their target genes. As such, the dysregulation of miRNA expression has been frequently linked to cancer. With rapidly accumulating molecular data linked to patient outcome, the need for identification of robust multi-omic molecular markers is critical in order to provide clinical impact. While previous bioinformatic tools have been developed to identify potential biomarkers in cancer, these methods do not allow for rapid classification of oncogenes versus tumor suppressors taking into account robust differential expression, cutoffs, p-values and non-normality of the data. Here, we propose a methodology, Robust Selection Algorithm (RSA) that addresses these important problems in big data omics analysis. The robustness of the survival analysis is ensured by identification of optimal cutoff values of omics expression, strengthened by p-value computed through intensive random resampling taking into account any non-normality in the data and integration into multi-omic functional networks. Here we have analyzed pan-cancer miRNA patient data to identify functional pathways involved in cancer progression that are associated with selected miRNA identified by RSA. Our approach demonstrates the way in which existing survival analysis techniques can be integrated with a functional network analysis framework to efficiently identify promising biomarkers and novel therapeutic candidates across diseases.

  6. A Large-Scale Multi-ancestry Genome-wide Study Accounting for Smoking Behavior Identifies Multiple Significant Loci for Blood Pressure

    Sung, Yun J; Winkler, Thomas W; de Las Fuentes, Lisa

    2018-01-01

    Genome-wide association analysis advanced understanding of blood pressure (BP), a major risk factor for vascular conditions such as coronary heart disease and stroke. Accounting for smoking behavior may help identify BP loci and extend our knowledge of its genetic architecture. We performed genom...

  7. A Large-Scale Multi-ancestry Genome-wide Study Accounting for Smoking Behavior Identifies Multiple Significant Loci for Blood Pressure

    Sung, Yun J.; Winkler, Thomas W.; de las Fuentes, Lisa; Bentley, Amy R.; Brown, Michael R.; Kraja, Aldi T.; Schwander, Karen; Ntalla, Ioanna; Guo, Xiuqing; Franceschini, Nora; Lu, Yingchang; Cheng, Ching-Yu; Sim, Xueling; Vojinovic, Dina; Marten, Jonathan; Musani, Solomon K.; Li, Changwei; Feitosa, Mary F.; Kilpelainen, Tuomas O.; Richard, Melissa A.; Noordam, Raymond; Aslibekyan, Stella; Aschard, Hugues; Bartz, Traci M.; Dorajoo, Rajkumar; Liu, Yongmei; Manning, Alisa K.; Rankinen, Tuomo; Smith, Albert Vernon; Tajuddin, Salman M.; Tayo, Bamidele O.; Warren, Helen R.; Zhao, Wei; Zhou, Yanhua; Matoba, Nana; Sofer, Tamar; Alver, Maris; Amini, Marzyeh; Boissel, Mathilde; Chai, Jin Fang; Chen, Xu; Divers, Jasmin; Gandin, Ilaria; Gao, Chuan; Giulianini, Franco; Goel, Anuj; Harris, Sarah E.; Hartwig, Fernando Pires; Horimoto, Andrea R. V. R.; Hsu, Fang-Chi; Jackson, Anne U.; Kahonen, Mika; Kasturiratne, Anuradhani; Kuhnel, Brigitte; Leander, Karin; Lee, Wen-Jane; Lin, Keng-Hung; Luan, Jian' an; McKenzie, Colin A.; He Meian,; Nelson, Christopher P.; Rauramaa, Rainer; Schupf, Nicole; Scott, Robert A.; Sheu, Wayne H. H.; Stancakova, Alena; Takeuchi, Fumihiko; van der Most, Peter J.; Varga, Tibor V.; Wang, Heming; Wang, Yajuan; Ware, Erin B.; Weiss, Stefan; Wen, Wanqing; Yanek, Lisa R.; Zhang, Weihua; Zhao, Jing Hua; Afaq, Saima; Alfred, Tamuno; Amin, Najaf; Arking, Dan; Aung, Tin; Barr, R. Graham; Bielak, Lawrence F.; Boerwinkle, Eric; Bottinger, Erwin P.; Braund, Peter S.; Brody, Jennifer A.; Broeckel, Ulrich; Cabrera, Claudia P.; Cade, Brian; Yu Caizheng,; Campbell, Archie; Canouil, Mickael; Chakravarti, Aravinda; Chauhan, Ganesh; Christensen, Kaare; Cocca, Massimiliano; Collins, Francis S.; Connell, John M.; de Mutsert, Renee; de Silva, H. Janaka; Debette, Stephanie; Dorr, Marcus; Duan, Qing; Eaton, Charles B.; Ehret, Georg; Evangelou, Evangelos; Faul, Jessica D.; Fisher, Virginia A.; Forouhi, Nita G.; Franco, Oscar H.; Friedlander, Yechiel; Gao, He; Gigante, Bruna; Graff, Misa; Gu, C. Charles; Gu, Dongfeng; Gupta, Preeti; Hagenaars, Saskia P.; Harris, Tamara B.; He, Jiang; Heikkinen, Sami; Heng, Chew-Kiat; Hirata, Makoto; Hofman, Albert; Howard, Barbara V.; Hunt, Steven; Irvin, Marguerite R.; Jia, Yucheng; Joehanes, Roby; Justice, Anne E.; Katsuya, Tomohiro; Kaufman, Joel; Kerrison, Nicola D.; Khor, Chiea Chuen; Koh, Woon-Puay; Koistinen, Heikki A.; Komulainen, Pirjo; Kooperberg, Charles; Krieger, Jose E.; Kubo, Michiaki; Kuusisto, Johanna; Langefeld, Carl D.; Langenberg, Claudia; Launer, Lenore J.; Lehne, Benjamin; Lewis, Cora E.; Li, Yize; Lim, Sing Hui; Lin, Shiow; Liu, Ching-Ti; Liu, Jianjun; Liu, Jingmin; Liu, Kiang; Liu, Yeheng; Loh, Marie; Lohman, Kurt K.; Long, Jirong; Louie, Tin; Magi, Reedik; Mahajan, Anubha; Meitinger, Thomas; Metspalu, Andres; Milani, Lili; Momozawa, Yukihide; Morris, Andrew P.; Mosley, Thomas H.; Munson, Peter; Murray, Alison D.; Nalls, Mike A.; Nasri, Ubaydah; Norris, Jill M.; North, Kari; Ogunniyi, Adesola; Padmanabhan, Sandosh; Palmas, Walter R.; Palmer, Nicholette D.; Pankow, James S.; Pedersen, Nancy L.; Peters, Annette; Peyser, Patricia A.; Polasek, Ozren; Raitakari, Olli T.; Renstrom, Frida; Rice, Treva K.; Ridker, Paul M.; Robino, Antonietta; Robinson, Jennifer G.; Rose, Lynda M.; Rudan, Igor; Sabanayagam, Charumathi; Salako, Babatunde L.; Sandow, Kevin; Schmidt, Carsten O.; Schreiner, Pamela J.; Scott, William R.; Seshadri, Sudha; Sever, Peter; Sitlani, Colleen M.; Smith, Jennifer A.; Snieder, Harold; Starr, John M.; Strauch, Konstantin; Tang, Hua; Taylor, Kent D.; Teo, Yik Ying; Tham, Yih Chung; Ultterlinden, Andre G.; Waldenberger, Melanie; Wang, Lihua; Wang, Ya X.; Bin Wei, Wen; Williams, Christine; Wilson, Gregory; Wojczynski, Mary K.; Yao, Jie; Yuan, Jian-Min; Zonderman, Alan B.; Becker, Diane M.; Boehnke, Michael; Bowden, Donald W.; Chambers, John C.; Chen, Yii-Der Ida; de Faire, Ulf; Deary, Ian J.; Esko, Tonu; Farrall, Martin; Forrester, Terrence; Franks, Paul W.; Freedman, Barry I.; Froguel, Philippe; Gasparini, Paolo; Gieger, Christian; Horta, Bernardo Lessa; Hung, Yi-Jen; Jonas, Jost B.; Kato, Norihiro; Kooner, Jaspal S.; Laakso, Markku; Lehtimaki, Terho; Liang, Kae-Woei; Magnusson, Patrik K. E.; Newman, Anne B.; Oldehinkel, Albertine J.; Pereira, Alexandre C.; Redline, Susan; Rettig, Rainer; Samani, Nilesh J.; Scott, James; Shu, Xiao-Ou; van der Harst, Pim; Wagenknecht, Lynne E.; Wareham, Nicholas J.; Watkins, Hugh; Weir, David R.; Wickremasinghe, Ananda R.; Wu, Tangchun; Zheng, Wei; Kamatani, Yoichiro; Laurie, Cathy C.; Bouchard, Claude; Cooper, Richard S.; Evans, Michele K.; Gudnason, Vilmundur; Kardia, Sharon L. R.; Kritchevsky, Stephen B.; Levy, Daniel; O'Connell, Jeff R.; Psaty, Bruce M.; van Dam, Rob M.; Sims, Mario; Arnett, Donna K.; Mook-Kanamori, Dennis O.; Kelly, Tanika N.; Fox, Ervin R.; Hayward, Caroline; Fornage, Myriam; Rotimi, Charles N.; Province, Michael A.; van Duijn, Cornelia M.; Tai, E. Shyong; Wong, Tien Yin; Loos, Ruth J. F.; Reiner, Alex P.; Rotter, Jerome I.; Zhu, Xiaofeng; Bierut, Laura J.; Gauderman, W. James; Caulfield, Mark J.; Elliott, Paul; Rice, Kenneth; Munroe, Patricia B.; Morrison, Alanna C.; Cupples, L. Adrienne; Rao, Dabeeru C.; Chasman, Daniel I.; Study, Lifelines Cohort

    2018-01-01

    Genome-wide association analysis advanced understanding of blood pressure (BP), a major risk factor for vascular conditions such as coronary heart disease and stroke. Accounting for smoking behavior may help identify BP loci and extend our knowledge of its genetic architecture. We performed

  8. Pyrolysis - gas chromatography - mass spectrometry of lignins

    Martin, F; Saiz-Jimenez, C; Gonzalez-Vila, F J

    1979-01-01

    Milled wood lignins from spruce, beech and bamboo were pyrolysed. The high-boiling products of pyrolysis were studied by GLC and mass spectrometry. The forty-three products identified provide information on the structural units of lignin.

  9. Mass Spectrometry in Clinical Laboratory: Applications in Therapeutic Drug Monitoring and Toxicology.

    Garg, Uttam; Zhang, Yan Victoria

    2016-01-01

    Mass spectrometry (MS) has been used in research and specialized clinical laboratories for decades as a very powerful technology to identify and quantify compounds. In recent years, application of MS in routine clinical laboratories has increased significantly. This is mainly due to the ability of MS to provide very specific identification, high sensitivity, and simultaneous analysis of multiple analytes (>100). The coupling of tandem mass spectrometry with gas chromatography (GC) or liquid chromatography (LC) has enabled the rapid expansion of this technology. While applications of MS are used in many clinical areas, therapeutic drug monitoring, drugs of abuse, and clinical toxicology are still the primary focuses of the field. It is not uncommon to see mass spectrometry being used in routine clinical practices for those applications.

  10. Multiple nuclear and mitochondrial genotyping identifies emperors and large-eye breams (Teleostei : Lethrinidae) from New Caledonia and reveals new large-eye bream species

    Borsa, Philippe; Collet, Adeline; Carassou, Laure; Ponton, Dominique; Chen, W. J.

    2010-01-01

    International audience; Species identification is fundamental to address questions about community ecology, biodiversity, conservation and resource management, at any life history stage. Current studies on fish larval ecology of tropical species are hampered by the lack of reliable and effective tools for identifying larvae at the species level. Emperors and large-eye breams comprise fish species from the perciform fish family Lethrinidae. They inhabit coastal and coral-reef habitats of the t...

  11. Multiple Genes Related to Muscle Identified through a Joint Analysis of a Two-stage Genome-wide Association Study for Racing Performance of 1,156 Thoroughbreds

    Dong-Hyun Shin

    2015-06-01

    Full Text Available Thoroughbred, a relatively recent horse breed, is best known for its use in horse racing. Although myostatin (MSTN variants have been reported to be highly associated with horse racing performance, the trait is more likely to be polygenic in nature. The purpose of this study was to identify genetic variants strongly associated with racing performance by using estimated breeding value (EBV for race time as a phenotype. We conducted a two-stage genome-wide association study to search for genetic variants associated with the EBV. In the first stage of genome-wide association study, a relatively large number of markers (~54,000 single-nucleotide polymorphisms, SNPs were evaluated in a small number of samples (240 horses. In the second stage, a relatively small number of markers identified to have large effects (170 SNPs were evaluated in a much larger number of samples (1,156 horses. We also validated the SNPs related to MSTN known to have large effects on racing performance and found significant associations in the stage two analysis, but not in stage one. We identified 28 significant SNPs related to 17 genes. Among these, six genes have a function related to myogenesis and five genes are involved in muscle maintenance. To our knowledge, these genes are newly reported for the genetic association with racing performance of Thoroughbreds. It complements a recent horse genome-wide association studies of racing performance that identified other SNPs and genes as the most significant variants. These results will help to expand our knowledge of the polygenic nature of racing performance in Thoroughbreds.

  12. Integrating genome-wide association study and expression quantitative trait loci data identifies multiple genes and gene set associated with neuroticism.

    Fan, Qianrui; Wang, Wenyu; Hao, Jingcan; He, Awen; Wen, Yan; Guo, Xiong; Wu, Cuiyan; Ning, Yujie; Wang, Xi; Wang, Sen; Zhang, Feng

    2017-08-01

    Neuroticism is a fundamental personality trait with significant genetic determinant. To identify novel susceptibility genes for neuroticism, we conducted an integrative analysis of genomic and transcriptomic data of genome wide association study (GWAS) and expression quantitative trait locus (eQTL) study. GWAS summary data was driven from published studies of neuroticism, totally involving 170,906 subjects. eQTL dataset containing 927,753 eQTLs were obtained from an eQTL meta-analysis of 5311 samples. Integrative analysis of GWAS and eQTL data was conducted by summary data-based Mendelian randomization (SMR) analysis software. To identify neuroticism associated gene sets, the SMR analysis results were further subjected to gene set enrichment analysis (GSEA). The gene set annotation dataset (containing 13,311 annotated gene sets) of GSEA Molecular Signatures Database was used. SMR single gene analysis identified 6 significant genes for neuroticism, including MSRA (p value=2.27×10 -10 ), MGC57346 (p value=6.92×10 -7 ), BLK (p value=1.01×10 -6 ), XKR6 (p value=1.11×10 -6 ), C17ORF69 (p value=1.12×10 -6 ) and KIAA1267 (p value=4.00×10 -6 ). Gene set enrichment analysis observed significant association for Chr8p23 gene set (false discovery rate=0.033). Our results provide novel clues for the genetic mechanism studies of neuroticism. Copyright © 2017. Published by Elsevier Inc.

  13. Analysis of Sheng-Mai-San, a Ginseng-Containing Multiple Components Traditional Chinese Herbal Medicine Using Liquid Chromatography Tandem Mass Spectrometry and Physical Examination by Electron and Light Microscopies

    Yung-Yi Cheng

    2016-09-01

    Full Text Available Sheng-Mai-San is a multi-component traditional Chinese herbal preparation. Due to the fact granulated additives, such as starch, carboxymethyl cellulose, lactose and raw herbal powder may alter the content of the bioactive markers in the herbal products, a developed ultra-high performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS method was used to measure the herbal biomarkers of ginsenoside Rb1, Rb2, Rc, Rd, Re, Rg1, Rh1, compound K, ophiopogonin D and schizandrin from the Sheng-Mai-San herbal formulation. Besides, scanning electron microscopy (SEM was used to observe the morphology of the herbal granular powders. Light microscopy with Congo red and iodine-KI reagent staining was used to identify the cellulose fiber and cornstarch added to pharmaceutical herbal products. The swelling power (SP, water solubility index (WSI, and crude fiber analysis were used to determine the contents of cellulose fiber and cornstarch in pharmaceutical herbal products. In this study, we developed a novel skill to assess the quantification of appended cornstarch in pharmaceutical herbal products using Aperio ImageScope software. Compared with the traditional cornstarch analysis, our analysis method is a rapid, simple and conversion process which could be applied to detect the percentage of added cornstarch in unknown powder products. The various range of the herbal content for the five pharmaceutical manufacturers varied by up to several hundreds-fold. The physical examination reveals that the morphology of the herbal pharmaceutical products is rough and irregular with sharp layers. This study provides a reference standard operating procedure guide for the quality control of the Chinese herbal pharmaceutical products of Sheng-Mai-San.

  14. Analysis of Sheng-Mai-San, a Ginseng-Containing Multiple Components Traditional Chinese Herbal Medicine Using Liquid Chromatography Tandem Mass Spectrometry and Physical Examination by Electron and Light Microscopies.

    Cheng, Yung-Yi; Tsai, Tung-Hu

    2016-09-01

    Sheng-Mai-San is a multi-component traditional Chinese herbal preparation. Due to the fact granulated additives, such as starch, carboxymethyl cellulose, lactose and raw herbal powder may alter the content of the bioactive markers in the herbal products, a developed ultra-high performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS) method was used to measure the herbal biomarkers of ginsenoside Rb₁, Rb₂, Rc, Rd, Re, Rg₁, Rh₁, compound K, ophiopogonin D and schizandrin from the Sheng-Mai-San herbal formulation. Besides, scanning electron microscopy (SEM) was used to observe the morphology of the herbal granular powders. Light microscopy with Congo red and iodine-KI reagent staining was used to identify the cellulose fiber and cornstarch added to pharmaceutical herbal products. The swelling power (SP), water solubility index (WSI), and crude fiber analysis were used to determine the contents of cellulose fiber and cornstarch in pharmaceutical herbal products. In this study, we developed a novel skill to assess the quantification of appended cornstarch in pharmaceutical herbal products using Aperio ImageScope software. Compared with the traditional cornstarch analysis, our analysis method is a rapid, simple and conversion process which could be applied to detect the percentage of added cornstarch in unknown powder products. The various range of the herbal content for the five pharmaceutical manufacturers varied by up to several hundreds-fold. The physical examination reveals that the morphology of the herbal pharmaceutical products is rough and irregular with sharp layers. This study provides a reference standard operating procedure guide for the quality control of the Chinese herbal pharmaceutical products of Sheng-Mai-San.

  15. Novel anti-c-Mpl monoclonal antibodies identified multiple differentially glycosylated human c-Mpl proteins in megakaryocytic cells but not in human solid tumors.

    Zhan, Jinghui; Felder, Barbara; Ellison, Aaron R; Winters, Aaron; Salimi-Moosavi, Hossein; Scully, Sheila; Turk, James R; Wei, Ping

    2013-06-01

    Thrombopoietin and its cognate receptor, c-Mpl, are the primary molecular regulators of megakaryocytopoiesis and platelet production. To date the pattern of c-Mpl expression in human solid tumors and the distribution and biochemical properties of c-Mpl proteins in hematopoietic tissues are largely unknown. We have recently developed highly specific mouse monoclonal antibodies (MAb) against human c-Mpl. In this study we used these antibodies to demonstrate the presence of full-length and truncated human c-Mpl proteins in various megakaryocytic cell types, and their absence in over 100 solid tumor cell lines and in the 12 most common primary human tumor types. Quantitative assays showed a cell context-dependent distribution of full-length and truncated c-Mpl proteins. All forms of human c-Mpl protein were found to be modified with extensive N-linked glycosylation but different degrees of sialylation and O-linked glycosylation. Of note, different variants of full-length c-Mpl protein exhibiting differential glycosylation were expressed in erythromegakaryocytic leukemic cell lines and in platelets from healthy human donors. This work provides a comprehensive analysis of human c-Mpl mRNA and protein expression on normal and malignant hematopoietic and non-hematopoietic cells and demonstrates the multiple applications of several novel anti-c-Mpl antibodies.

  16. Transcriptome-wide analysis of the Trypanosoma cruzi proliferative cycle identifies the periodically expressed mRNAs and their multiple levels of control.

    Santiago Chávez

    Full Text Available Trypanosoma cruzi is the protozoan parasite causing American trypanosomiasis or Chagas disease, a neglected parasitosis with important human health impact in Latin America. The efficacy of current therapy is limited, and its toxicity is high. Since parasite proliferation is a fundamental target for rational drug design, we sought to progress into its understanding by applying a genome-wide approach. Treating a TcI linage strain with hydroxyurea, we isolated epimastigotes in late G1, S and G2/M cell cycle stages at 70% purity. The sequencing of each phase identified 305 stage-specific transcripts (1.5-fold change, p≤0.01, coding for conserved cell cycle regulated proteins and numerous proteins whose cell cycle dependence has not been recognized before. Comparisons with the parasite T. brucei and the human host reveal important differences. The meta-analysis of T. cruzi transcriptomic and ribonomic data indicates that cell cycle regulated mRNAs are subject to sub-cellular compartmentalization. Compositional and structural biases of these genes- including CAI, GC content, UTR length, and polycistron position- may contribute to their regulation. To discover nucleotide motifs responsible for the co-regulation of cell cycle regulated genes, we looked for overrepresented motifs at their UTRs and found a variant of the cell cycle sequence motif at the 3' UTR of most of the S and G2 stage genes. We additionally identified hairpin structures at the 5' UTRs of a high proportion of the transcripts, suggesting that periodic gene expression might also rely on translation initiation in T. cruzi. In summary, we report a comprehensive list of T. cruzi cell cycle regulated genes, including many previously unstudied proteins, we show evidence favoring a multi-step control of their expression, and we identify mRNA motifs that may mediate their regulation. Our results provide novel information of the T. cruzi proliferative proteins and the integrated levels of

  17. Multiple 5' ends of human cytomegalovirus UL57 transcripts identify a complex, cycloheximide-resistant promoter region that activates oriLyt

    Kiehl, Anita; Huang, Lili; Franchi, David; Anders, David G.

    2003-01-01

    The human cytomegalovirus (HCMV) UL57 gene lies adjacent to HCMV oriLyt, from which it is separated by an organizationally conserved, mostly noncoding region that is thought to both regulate UL57 expression and activate oriLyt function. However, the UL57 promoter has not been studied. We determined the 5' ends of UL57 transcripts toward an understanding of the potential relationship between UL57 expression and oriLyt activation. The results presented here identified three distinct 5' ends spread over 800 bp, at nt 90302, 90530, and 91138; use of these sites exhibited differential sensitivity to phosphonoformic acid treatment. Interestingly, a 10-kb UL57 transcript accumulated in cycloheximide-treated infected cells, even though other early transcripts were not detectable. However, the 10-kb transcript did not accumulate in cells treated with the more stringent translation inhibitor anisomycin. Consistent with the notion that the identified 5' ends arise from distinct transcription start sites, the sequences upstream of sites I and II functioned as promoters responsive to HCMV infection in transient assays. However, the origin-proximal promoter region III required downstream sequences for transcriptional activity. Mutation of candidate core promoter elements suggested that promoter III is regulated by an initiator region (Inr) and a downstream promoter element. Finally, a 42-bp sequence containing the candidate Inr activated a minimal oriLyt core construct in transient replication assays. Thus, these studies showed that a large, complex promoter region with novel features controls UL57 expression, and identified a sequence that regulates both UL57 transcription and oriLyt activation

  18. Structural and functional screening in human induced-pluripotent stem cell-derived cardiomyocytes accurately identifies cardiotoxicity of multiple drug types

    Doherty, Kimberly R., E-mail: kimberly.doherty@quintiles.com; Talbert, Dominique R.; Trusk, Patricia B.; Moran, Diarmuid M.; Shell, Scott A.; Bacus, Sarah

    2015-05-15

    Safety pharmacology studies that evaluate new drug entities for potential cardiac liability remain a critical component of drug development. Current studies have shown that in vitro tests utilizing human induced pluripotent stem cell-derived cardiomyocytes (hiPS-CM) may be beneficial for preclinical risk evaluation. We recently demonstrated that an in vitro multi-parameter test panel assessing overall cardiac health and function could accurately reflect the associated clinical cardiotoxicity of 4 FDA-approved targeted oncology agents using hiPS-CM. The present studies expand upon this initial observation to assess whether this in vitro screen could detect cardiotoxicity across multiple drug classes with known clinical cardiac risks. Thus, 24 drugs were examined for their effect on both structural (viability, reactive oxygen species generation, lipid formation, troponin secretion) and functional (beating activity) endpoints in hiPS-CM. Using this screen, the cardiac-safe drugs showed no effects on any of the tests in our panel. However, 16 of 18 compounds with known clinical cardiac risk showed drug-induced changes in hiPS-CM by at least one method. Moreover, when taking into account the Cmax values, these 16 compounds could be further classified depending on whether the effects were structural, functional, or both. Overall, the most sensitive test assessed cardiac beating using the xCELLigence platform (88.9%) while the structural endpoints provided additional insight into the mechanism of cardiotoxicity for several drugs. These studies show that a multi-parameter approach examining both cardiac cell health and function in hiPS-CM provides a comprehensive and robust assessment that can aid in the determination of potential cardiac liability. - Highlights: • 24 drugs were tested for cardiac liability using an in vitro multi-parameter screen. • Changes in beating activity were the most sensitive in predicting cardiac risk. • Structural effects add in

  19. Application of multiple-isotope and groundwater-age data to identify factors affecting the extent of denitrification in a shallow aquifer near a river in South Korea

    Kaown, Dugin; Koh, Eun-Hee; Mayer, Bernhard; Kim, Heejung; Park, Dong Kyu; Park, Byeong-Hak; Lee, Kang-Kun

    2018-01-01

    The extent of denitrification in a small agricultural area near a river in Yangpyeong, South Korea, was determined using multiple isotopes, groundwater age, and physicochemical data for groundwater. The shallow groundwater at one monitoring site had high concentrations of NO3-N (74-83 mg L-1). The δ15N-NO3 values for groundwater in the study area ranged between +9.1 and +24.6‰ in June 2014 and +12.2 to +21.6‰ in October 2014. High δ15N-NO3 values (+10.7 to +12.5‰) in both sampling periods indicated that the high concentrations of nitrate in the groundwater originated from application of organic fertilizers and manure. In the northern part of the study area, some groundwater samples showed elevated δ15N-NO3 and δ18O-NO3 values, which suggest that nitrate was removed from the groundwater via denitrification, with N isotope enrichment factors ranging between -4.8 and -7.9‰ and O isotope enrichment factors varying between -3.8 and -4.9‰. Similar δD and δ18O values of the surface water and groundwater in the south appear to indicate that groundwater in that area was affected by surface-water infiltration. The mean residence times (MRTs) of groundwater showed younger ages in the south (10-20 years) than in the north (20-30 years). Hence, it was concluded that denitrification processes under anaerobic conditions with longer groundwater MRT in the northern part of the study area removed considerable amounts of nitrate. This study demonstrates that multi-isotope data combined with physicochemical data and age-dating information can be effectively applied to characterize nitrate contaminant sources and attenuation processes.

  20. EcoIP: An Open Source Image Analysis Toolkit to Identify Different Stages of Plant Phenology for Multiple Species with Pan-Tilt-Zoom Cameras

    Granados, Joel; Bonnet, Philippe

    2013-01-01

    Because of the increased number of cameras employed in environmental sensing and the tremendous image output they produce, we have created a flexible, open-source software solution called EcoIP to help automatically determine different phenophases for different species from digital image sequences....... Onset and ending dates are calculated through an iterative process: (1) training images are chosen and areas of interest identified, (2) separation of foreground and background is accomplished based on a naive Bayesian method, (3) a signal is created based on the separation model and (4) it is then fit...... to a sigmoid that contains the dates of interest. Results using different phenological events of different species indicate that estimated dates fall within a few days of the observed dates for most cases. Our experiments indicate that color separability and scene illumination are contributing factors...

  1. Multiple Identified Neurons and Peripheral Nerves Innervating the Prothoracic Defense Glands in Stick Insects Reveal Evolutionary Conserved and Novel Elements of a Chemical Defense System

    Johannes Strauß

    2017-11-01

    Full Text Available The defense glands in the dorsal prothorax are an important autapomorphic trait of stick insects (Phasmatodea. Here, we study the functional anatomy and neuronal innervation of the defense glands in Anisomorpha paromalus (Westwood, 1859 (Pseudophasmatinae, a species which sprays its defense secretions when disturbed or attacked. We use a neuroanatomical approach to identify the nerves innervating the gland muscles and the motoneurons with axons in the different nerves. The defense gland is innervated by nerves originating from two segments, the subesophageal ganglion (SOG, and the prothoracic ganglion. Axonal tracing confirms the gland innervation via the anterior subesophageal nerve, and two intersegmental nerves, the posterior subesophageal nerve, and the anterior prothoracic nerve. Axonal tracing of individual nerves reveals eight identified neuron types in the subesophageal or prothoracic ganglion. The strongest innervating nerve of the gland is the anterior subesophageal nerve, which also supplies dorsal longitudinal thorax muscles (neck muscles by separate nerve branches. Tracing of individual nerve branches reveals different sets of motoneurons innervating the defense gland (one ipsilateral and one contralateral subesophageal neuron or the neck muscle (ventral median neurons. The ipsilateral and contralateral subesophageal neurons have no homologs in related taxa like locusts and crickets, and thus evolved within stick insects with the differentiation of the defense glands. The overall innervation pattern suggests that the longitudinal gland muscles derived from dorsal longitudinal neck muscles. In sum, the innervating nerves for dorsal longitudinal muscles are conserved in stick insects, while the neuronal control system was specialized with conserved motoneurons for the persisting neck muscles, and evolutionarily novel subesophageal and prothoracic motoneurons innervating the defense gland.

  2. Gene-based association identifies SPATA13-AS1 as a pharmacogenomic predictor of inhaled short-acting beta-agonist response in multiple population groups.

    Padhukasahasram, B; Yang, J J; Levin, A M; Yang, M; Burchard, E G; Kumar, R; Kwok, P-Y; Seibold, M A; Lanfear, D E; Williams, L K

    2014-08-01

    Inhaled short-acting beta-agonist (SABA) medication is commonly used in asthma patients to rapidly reverse airway obstruction and improve acute symptoms. We performed a genome-wide association study of SABA medication response using gene-based association tests. A linear mixed model approach was first used for single-nucleotide polymorphism associations, and the results were later combined using GATES to generate gene-based associations. Our results identified SPATA13-AS1 as being significantly associated with SABA bronchodilator response in 328 healthy African Americans. In replication, this gene was associated with SABA response among the two separate groups of African Americans with asthma (n=1073, P=0.011 and n=1968, P=0.014), 149 healthy African Americans (P=0.003) and 556 European Americans with asthma (P=0.041). SPATA13-AS1 was also associated with longitudinal SABA medication usage in the two separate groups of African Americans with asthma (n=658, P=0.047 and n=1968, P=0.025). Future studies are needed to delineate the precise mechanism by which SPATA13-AS1 may influence SABA response.

  3. Sequencing of a patient with balanced chromosome abnormalities and neurodevelopmental disease identifies disruption of multiple high risk loci by structural variation.

    Jonathon Blake

    Full Text Available Balanced chromosome abnormalities (BCAs occur at a high frequency in healthy and diseased individuals, but cost-efficient strategies to identify BCAs and evaluate whether they contribute to a phenotype have not yet become widespread. Here we apply genome-wide mate-pair library sequencing to characterize structural variation in a patient with unclear neurodevelopmental disease (NDD and complex de novo BCAs at the karyotype level. Nucleotide-level characterization of the clinically described BCA breakpoints revealed disruption of at least three NDD candidate genes (LINC00299, NUP205, PSMD14 that gave rise to abnormal mRNAs and could be assumed as disease-causing. However, unbiased genome-wide analysis of the sequencing data for cryptic structural variation was key to reveal an additional submicroscopic inversion that truncates the schizophrenia- and bipolar disorder-associated brain transcription factor ZNF804A as an equally likely NDD-driving gene. Deep sequencing of fluorescent-sorted wild-type and derivative chromosomes confirmed the clinically undetected BCA. Moreover, deep sequencing further validated a high accuracy of mate-pair library sequencing to detect structural variants larger than 10 kB, proposing that this approach is powerful for clinical-grade genome-wide structural variant detection. Our study supports previous evidence for a role of ZNF804A in NDD and highlights the need for a more comprehensive assessment of structural variation in karyotypically abnormal individuals and patients with neurocognitive disease to avoid diagnostic deception.

  4. Genome-wide Meta-analyses of Breast, Ovarian and Prostate Cancer Association Studies Identify Multiple New Susceptibility Loci Shared by At Least Two Cancer Types

    Kar, Siddhartha P.; Beesley, Jonathan; Al Olama, Ali Amin; Michailidou, Kyriaki; Tyrer, Jonathan; Kote-Jarai, ZSofia; Lawrenson, Kate; Lindstrom, Sara; Ramus, Susan J.; Thompson, Deborah J.; Kibel, Adam S.; Dansonka-Mieszkowska, Agnieszka; Michael, Agnieszka; Dieffenbach, Aida K.; Gentry-Maharaj, Aleksandra; Whittemore, Alice S.; Wolk, Alicja; Monteiro, Alvaro; Peixoto, Ana; Kierzek, Andrzej; Cox, Angela; Rudolph, Anja; Gonzalez-Neira, Anna; Wu, Anna H.; Lindblom, Annika; Swerdlow, Anthony; Ziogas, Argyrios; Ekici, Arif B.; Burwinkel, Barbara; Karlan, Beth Y.; Nordestgaard, Børge G.; Blomqvist, Carl; Phelan, Catherine; McLean, Catriona; Pearce, Celeste Leigh; Vachon, Celine; Cybulski, Cezary; Slavov, Chavdar; Stegmaier, Christa; Maier, Christiane; Ambrosone, Christine B.; Høgdall, Claus K.; Teerlink, Craig C.; Kang, Daehee; Tessier, Daniel C.; Schaid, Daniel J.; Stram, Daniel O.; Cramer, Daniel W.; Neal, David E.; Eccles, Diana; Flesch-Janys, Dieter; Velez Edwards, Digna R.; Wokozorczyk, Dominika; Levine, Douglas A.; Yannoukakos, Drakoulis; Sawyer, Elinor J.; Bandera, Elisa V.; Poole, Elizabeth M.; Goode, Ellen L.; Khusnutdinova, Elza; Høgdall, Estrid; Song, Fengju; Bruinsma, Fiona; Heitz, Florian; Modugno, Francesmary; Hamdy, Freddie C.; Wiklund, Fredrik; Giles, Graham G.; Olsson, Håkan; Wildiers, Hans; Ulmer, Hans-Ulrich; Pandha, Hardev; Risch, Harvey A.; Darabi, Hatef; Salvesen, Helga B.; Nevanlinna, Heli; Gronberg, Henrik; Brenner, Hermann; Brauch, Hiltrud; Anton-Culver, Hoda; Song, Honglin; Lim, Hui-Yi; McNeish, Iain; Campbell, Ian; Vergote, Ignace; Gronwald, Jacek; Lubiński, Jan; Stanford, Janet L.; Benítez, Javier; Doherty, Jennifer A.; Permuth, Jennifer B.; Chang-Claude, Jenny; Donovan, Jenny L.; Dennis, Joe; Schildkraut, Joellen M.; Schleutker, Johanna; Hopper, John L.; Kupryjanczyk, Jolanta; Park, Jong Y.; Figueroa, Jonine; Clements, Judith A.; Knight, Julia A.; Peto, Julian; Cunningham, Julie M.; Pow-Sang, Julio; Batra, Jyotsna; Czene, Kamila; Lu, Karen H.; Herkommer, Kathleen; Khaw, Kay-Tee; Matsuo, Keitaro; Muir, Kenneth; Offitt, Kenneth; Chen, Kexin; Moysich, Kirsten B.; Aittomäki, Kristiina; Odunsi, Kunle; Kiemeney, Lambertus A.; Massuger, Leon F.A.G.; Fitzgerald, Liesel M.; Cook, Linda S.; Cannon-Albright, Lisa; Hooning, Maartje J.; Pike, Malcolm C.; Bolla, Manjeet K.; Luedeke, Manuel; Teixeira, Manuel R.; Goodman, Marc T.; Schmidt, Marjanka K.; Riggan, Marjorie; Aly, Markus; Rossing, Mary Anne; Beckmann, Matthias W.; Moisse, Matthieu; Sanderson, Maureen; Southey, Melissa C.; Jones, Michael; Lush, Michael; Hildebrandt, Michelle A. T.; Hou, Ming-Feng; Schoemaker, Minouk J.; Garcia-Closas, Montserrat; Bogdanova, Natalia; Rahman, Nazneen; Le, Nhu D.; Orr, Nick; Wentzensen, Nicolas; Pashayan, Nora; Peterlongo, Paolo; Guénel, Pascal; Brennan, Paul; Paulo, Paula; Webb, Penelope M.; Broberg, Per; Fasching, Peter A.; Devilee, Peter; Wang, Qin; Cai, Qiuyin; Li, Qiyuan; Kaneva, Radka; Butzow, Ralf; Kopperud, Reidun Kristin; Schmutzler, Rita K.; Stephenson, Robert A.; MacInnis, Robert J.; Hoover, Robert N.; Winqvist, Robert; Ness, Roberta; Milne, Roger L.; Travis, Ruth C.; Benlloch, Sara; Olson, Sara H.; McDonnell, Shannon K.; Tworoger, Shelley S.; Maia, Sofia; Berndt, Sonja; Lee, Soo Chin; Teo, Soo-Hwang; Thibodeau, Stephen N.; Bojesen, Stig E.; Gapstur, Susan M.; Kjær, Susanne Krüger; Pejovic, Tanja; Tammela, Teuvo L.J.; Dörk, Thilo; Brüning, Thomas; Wahlfors, Tiina; Key, Tim J.; Edwards, Todd L.; Menon, Usha; Hamann, Ute; Mitev, Vanio; Kosma, Veli-Matti; Setiawan, Veronica Wendy; Kristensen, Vessela; Arndt, Volker; Vogel, Walther; Zheng, Wei; Sieh, Weiva; Blot, William J.; Kluzniak, Wojciech; Shu, Xiao-Ou; Gao, Yu-Tang; Schumacher, Fredrick; Freedman, Matthew L.; Berchuck, Andrew; Dunning, Alison M.; Simard, Jacques; Haiman, Christopher A.; Spurdle, Amanda; Sellers, Thomas A.; Hunter, David J.; Henderson, Brian E.; Kraft, Peter; Chanock, Stephen J.; Couch, Fergus J.; Hall, Per; Gayther, Simon A.; Easton, Douglas F.; Chenevix-Trench, Georgia; Eeles, Rosalind; Pharoah, Paul D.P.; Lambrechts, Diether

    2016-01-01

    Breast, ovarian, and prostate cancers are hormone-related and may have a shared genetic basis but this has not been investigated systematically by genome-wide association (GWA) studies. Meta-analyses combining the largest GWA meta-analysis data sets for these cancers totaling 112,349 cases and 116,421 controls of European ancestry, all together and in pairs, identified at P cancer loci: three associated with susceptibility to all three cancers (rs17041869/2q13/BCL2L11; rs7937840/11q12/INCENP; rs1469713/19p13/GATAD2A), two breast and ovarian cancer risk loci (rs200182588/9q31/SMC2; rs8037137/15q26/RCCD1), and two breast and prostate cancer risk loci (rs5013329/1p34/NSUN4; rs9375701/6q23/L3MBTL3). Index variants in five additional regions previously associated with only one cancer also showed clear association with a second cancer type. Cell-type specific expression quantitative trait locus and enhancer-gene interaction annotations suggested target genes with potential cross-cancer roles at the new loci. Pathway analysis revealed significant enrichment of death receptor signaling genes near loci with P cancer meta-analysis. PMID:27432226

  5. Sequencing of a Patient with Balanced Chromosome Abnormalities and Neurodevelopmental Disease Identifies Disruption of Multiple High Risk Loci by Structural Variation

    Blake, Jonathon; Riddell, Andrew; Theiss, Susanne; Gonzalez, Alexis Perez; Haase, Bettina; Jauch, Anna; Janssen, Johannes W. G.; Ibberson, David; Pavlinic, Dinko; Moog, Ute; Benes, Vladimir; Runz, Heiko

    2014-01-01

    Balanced chromosome abnormalities (BCAs) occur at a high frequency in healthy and diseased individuals, but cost-efficient strategies to identify BCAs and evaluate whether they contribute to a phenotype have not yet become widespread. Here we apply genome-wide mate-pair library sequencing to characterize structural variation in a patient with unclear neurodevelopmental disease (NDD) and complex de novo BCAs at the karyotype level. Nucleotide-level characterization of the clinically described BCA breakpoints revealed disruption of at least three NDD candidate genes (LINC00299, NUP205, PSMD14) that gave rise to abnormal mRNAs and could be assumed as disease-causing. However, unbiased genome-wide analysis of the sequencing data for cryptic structural variation was key to reveal an additional submicroscopic inversion that truncates the schizophrenia- and bipolar disorder-associated brain transcription factor ZNF804A as an equally likely NDD-driving gene. Deep sequencing of fluorescent-sorted wild-type and derivative chromosomes confirmed the clinically undetected BCA. Moreover, deep sequencing further validated a high accuracy of mate-pair library sequencing to detect structural variants larger than 10 kB, proposing that this approach is powerful for clinical-grade genome-wide structural variant detection. Our study supports previous evidence for a role of ZNF804A in NDD and highlights the need for a more comprehensive assessment of structural variation in karyotypically abnormal individuals and patients with neurocognitive disease to avoid diagnostic deception. PMID:24625750

  6. An in vivo cis-regulatory screen at the type 2 diabetes associated TCF7L2 locus identifies multiple tissue-specific enhancers.

    Daniel Savic

    Full Text Available Genome-wide association studies (GWAS have repeatedly shown an association between non-coding variants in the TCF7L2 locus and risk for type 2 diabetes (T2D, implicating a role for cis-regulatory variation within this locus in disease etiology. Supporting this hypothesis, we previously localized complex regulatory activity to the TCF7L2 T2D-associated interval using an in vivo bacterial artificial chromosome (BAC enhancer-trapping reporter strategy. To follow-up on this broad initial survey of the TCF7L2 regulatory landscape, we performed a fine-mapping enhancer scan using in vivo mouse transgenic reporter assays. We functionally interrogated approximately 50% of the sequences within the T2D-associated interval, utilizing sequence conservation within this 92-kb interval to determine the regulatory potential of all evolutionary conserved sequences that exhibited conservation to the non-eutherian mammal opossum. Included in this study was a detailed functional interrogation of sequences spanning both protective and risk alleles of single nucleotide polymorphism (SNP rs7903146, which has exhibited allele-specific enhancer function in pancreatic beta cells. Using these assays, we identified nine segments regulating various aspects of the TCF7L2 expression profile and that constitute nearly 70% of the sequences tested. These results highlight the regulatory complexity of this interval and support the notion that a TCF7L2 cis-regulatory disruption leads to T2D predisposition.

  7. Reactor gamma spectrometry: status

    Gold, R.; Kaiser, B.J.

    1979-01-01

    Current work is described for Compton Recoil Gamma-Ray Spectrometry including developments in experimental technique as well as recent reactor spectrometry measurements. The current status of the method is described concerning gamma spectromoetry probe design and response characteristics. Emphasis is given to gamma spectrometry work in US LWR and BR programs. Gamma spectrometry in BR environments are outlined by focussing on start-up plans for the Fast Test Reactor (FTR). Gamma spectrometry results are presented for a LWR pressure vessel mockup in the Poolside Critical Assembly (PCA) at Oak Ridge National Laboratory

  8. Using portable X-ray fluorescence spectrometry and GIS to assess environmental risk and identify sources of trace metals in soils of peri-urban areas in the Yangtze Delta region, China.

    Ran, Jing; Wang, Dejian; Wang, Can; Zhang, Gang; Yao, Lipeng

    2014-08-01

    Portable X-ray fluorescence (PXRF) spectrometry may be very suitable for a fast and effective environmental assessment and source identification of trace metals in soils. In this study, topsoils (0-10 cm) at 139 sites were in situ scanned for total trace metals (Cr, Cu, Ni, Pb and Zn) and arsenic concentrations by PXRF in a typical town in Yangtze Delta region of Jiangsu province, China. To validate the utility of PXRF, 53 samples were collected from the scanning sites for the determination of selected trace metals using conventional methods. Based on trace metal concentrations detected by in situ PXRF, the contamination extent and sources of trace metals were studied via geo-accumulation index, multivariate analysis and geostatistics. The trace metal concentrations determined by PXRF were similar to those obtained via conventional chemical analysis. The median concentration of As, Cr, Cu, Ni, Pb and Zn in soils were 10.8, 56.4, 41.5, 43.5, 33.5, and 77.7 mg kg(-1), respectively. The distribution patterns of Cr, Cu, Ni, Pb, and Zn were mostly affected by anthropogenic sources, while As was mainly derived from lithogenic sources. Overall, PXRF has been successfully applied to contamination assessment and source identification of trace metals in soils.

  9. Linked Patient-Reported Outcomes Data From Patients With Multiple Sclerosis Recruited on an Open Internet Platform to Health Care Claims Databases Identifies a Representative Population for Real-Life Data Analysis in Multiple Sclerosis.

    Risson, Valery; Ghodge, Bhaskar; Bonzani, Ian C; Korn, Jonathan R; Medin, Jennie; Saraykar, Tanmay; Sengupta, Souvik; Saini, Deepanshu; Olson, Melvin

    2016-09-22

    An enormous amount of information relevant to public health is being generated directly by online communities. To explore the feasibility of creating a dataset that links patient-reported outcomes data, from a Web-based survey of US patients with multiple sclerosis (MS) recruited on open Internet platforms, to health care utilization information from health care claims databases. The dataset was generated by linkage analysis to a broader MS population in the United States using both pharmacy and medical claims data sources. US Facebook users with an interest in MS were alerted to a patient-reported survey by targeted advertisements. Eligibility criteria were diagnosis of MS by a specialist (primary progressive, relapsing-remitting, or secondary progressive), ≥12-month history of disease, age 18-65 years, and commercial health insurance. Participants completed a questionnaire including data on demographic and disease characteristics, current and earlier therapies, relapses, disability, health-related quality of life, and employment status and productivity. A unique anonymous profile was generated for each survey respondent. Each anonymous profile was linked to a number of medical and pharmacy claims datasets in the United States. Linkage rates were assessed and survey respondents' representativeness was evaluated based on differences in the distribution of characteristics between the linked survey population and the general MS population in the claims databases. The advertisement was placed on 1,063,973 Facebook users' pages generating 68,674 clicks, 3719 survey attempts, and 651 successfully completed surveys, of which 440 could be linked to any of the claims databases for 2014 or 2015 (67.6% linkage rate). Overall, no significant differences were found between patients who were linked and not linked for educational status, ethnicity, current or prior disease-modifying therapy (DMT) treatment, or presence of a relapse in the last 12 months. The frequencies of the

  10. Identified Hadron Production as a Function of Event Multiplicity and Transverse Spherocity in pp Collisions at $\\sqrt{s}$ = 7 and 13 TeV with the ALICE Detector

    AUTHOR|(INSPIRE)INSPIRE-00510339; Oskarsson, Anders; Silvermyr, David

    This study reports on identified hadron production as a function of event multiplicity ($\\langle\\textrm{d}N_{\\textrm{ch}}/\\textrm{d}η\\rangle$) and transverse spherocity ($S_\\textrm{O}$ ) in proton-proton collisions at $\\sqrt{s}$ = 7 and 13 TeV measured with the ALICE detector at the LHC. The particle spectra and their ratios measured in high-multiplicity events show signatures of an expanding medium. Integrated particle yields as a function of multiplicity measured in pp collisions at $\\sqrt{s}$ = 7 and 13 TeV are compared to those measured in p-Pb and Pb-Pb collisions. Hadrochemical composition of particles are found to be similar in different colliding systems under different $\\sqrt{s}$, provided similar multiplicities are compared. This suggests that hadron yields are dominantly driven by $\\langle\\textrm{d}N_{\\textrm{ch}}/\\textrm{d}η\\rangle$, and not the colliding system or center-of-mass energy. On the other hand, particle spectra measured in pp collisions at $\\sqrt{s}$ = 13 TeV is harder than that at 7...

  11. A new multiple regression model to identify multi-family houses with a high prevalence of sick building symptoms "SBS", within the healthy sustainable house study in Stockholm (3H).

    Engvall, Karin; Hult, M; Corner, R; Lampa, E; Norbäck, D; Emenius, G

    2010-01-01

    The aim was to develop a new model to identify residential buildings with higher frequencies of "SBS" than expected, "risk buildings". In 2005, 481 multi-family buildings with 10,506 dwellings in Stockholm were studied by a new stratified random sampling. A standardised self-administered questionnaire was used to assess "SBS", atopy and personal factors. The response rate was 73%. Statistical analysis was performed by multiple logistic regressions. Dwellers owning their building reported less "SBS" than those renting. There was a strong relationship between socio-economic factors and ownership. The regression model, ended up with high explanatory values for age, gender, atopy and ownership. Applying our model, 9% of all residential buildings in Stockholm were classified as "risk buildings" with the highest proportion in houses built 1961-1975 (26%) and lowest in houses built 1985-1990 (4%). To identify "risk buildings", it is necessary to adjust for ownership and population characteristics.

  12. Mass spectrometry of long-lived radionuclides

    Becker, Johanna Sabine.

    2003-01-01

    The capability of determining element concentrations at the trace and ultratrace level and isotope ratios is a main feature of inorganic mass spectrometry. The precise and accurate determination of isotope ratios of long-lived natural and artificial radionuclides is required, e.g. for their environmental monitoring and health control, for studying radionuclide migration, for age dating, for determining isotope ratios of radiogenic elements in the nuclear industry, for quality assurance and determination of the burn-up of fuel material in a nuclear power plant, for reprocessing plants, nuclear material accounting and radioactive waste control. Inorganic mass spectrometry, especially inductively coupled plasma mass spectrometry (ICP-MS) as the most important inorganic mass spectrometric technique today, possesses excellent sensitivity, precision and good accuracy for isotope ratio measurements and practically no restriction with respect to the ionization potential of the element investigated--therefore, thermal ionization mass spectrometry (TIMS), which has been used as the dominant analytical technique for precise isotope ratio measurements of long-lived radionuclides for many decades, is being replaced increasingly by ICP-MS. In the last few years instrumental progress in improving figures of merit for the determination of isotope ratio measurements of long-lived radionuclides in ICP-MS has been achieved by the application of a multiple ion collector device (MC-ICP-MS) and the introduction of the collision cell interface in order to dissociate disturbing argon-based molecular ions, to reduce the kinetic energy of ions and neutralize the disturbing noble gas ions (e.g. of 129 Xe + for the determination of 129 I). The review describes the state of the art and the progress of different inorganic mass spectrometric techniques such as ICP-MS, laser ablation ICP-MS vs. TIMS, glow discharge mass spectrometry, secondary ion mass spectrometry, resonance ionization mass

  13. Methods of neutron spectrometry

    Doerschel, B.

    1981-01-01

    The different methods of neutron spectrometry are based on the direct measurement of neutron velocity or on the use of suitable energy-dependent interaction processes. In the latter case the measuring effect of a detector is connected with the searched neutron spectrum by an integral equation. The solution needs suitable unfolding procedures. The most important methods of neutron spectrometry are the time-of-flight method, the crystal spectrometry, the neutron spectrometry by use of elastic collisions with hydrogen nuclei, and neutron spectrometry with the aid of nuclear reactions, especially of the neutron-induced activation. The advantages and disadvantages of these methods are contrasted considering the resolution, the measurable energy range, the sensitivity, and the experimental and computational efforts. (author)

  14. Alpha spectrometry and the secondary ion mass spectrometry of thorium

    Strisovska, J.; Kuruc, J.; Galanda, D.; Matel, L.; Aranyosiova, M.; Velic, D.

    2009-01-01

    The main objective of this master thesis was preparation of samples with thorium content on the steel discs by electrodeposition for determination of natural thorium isotope by alpha spectrometry and the secondary ion mass spectrometry and finding out their possible linear correlation between these methods. The samples with electrolytically excluded isotope of 232 Th were prepared by electrodeposition from solution Th(NO 3 ) 4 ·12 H2 O on steel discs in electrodeposition cell with use of solutions Na 2 SO 4 , NaHSO 4 , KOH and (NH 4 ) 2 (C 2 O 4 ) by electric current 0.75 A. Discs were measured by alpha spectrometer. Activity was calculated from the registered impulses for 232 Th and surface's weight. After alpha spectrometry measurements discs were analyzed by TOF-SIMS IV which is installed in the International Laser Centre in Bratislava. Intensities of isotope of 232 Th and ions of ThO + , ThOH + , ThO 2 H + , Th 2 O 4 H + , ThO 2 - , ThO 3 H - , ThH 3 O 3 - and ThN 2 O 5 H - were identified. The linear correlation is between surface's weights of Th and intensities of ions of Th + from SIMS, however the correlation coefficient has relatively low value. We found out with SIMS method that oxidized and hydride forms of thorium are significantly represented in samples with electroplated thorium. (authors)

  15. Immunochip analyses identify a novel risk locus for primary biliary cirrhosis at 13q14, multiple independent associations at four established risk loci and epistasis between 1p31 and 7q32 risk variants

    Juran, Brian D.; Hirschfield, Gideon M.; Invernizzi, Pietro; Atkinson, Elizabeth J.; Li, Yafang; Xie, Gang; Kosoy, Roman; Ransom, Michael; Sun, Ye; Bianchi, Ilaria; Schlicht, Erik M.; Lleo, Ana; Coltescu, Catalina; Bernuzzi, Francesca; Podda, Mauro; Lammert, Craig; Shigeta, Russell; Chan, Landon L.; Balschun, Tobias; Marconi, Maurizio; Cusi, Daniele; Heathcote, E. Jenny; Mason, Andrew L.; Myers, Robert P.; Milkiewicz, Piotr; Odin, Joseph A.; Luketic, Velimir A.; Bacon, Bruce R.; Bodenheimer, Henry C.; Liakina, Valentina; Vincent, Catherine; Levy, Cynthia; Franke, Andre; Gregersen, Peter K.; Bossa, Fabrizio; Gershwin, M. Eric; deAndrade, Mariza; Amos, Christopher I.; Lazaridis, Konstantinos N.; Seldin, Michael F.; Siminovitch, Katherine A.

    2012-01-01

    To further characterize the genetic basis of primary biliary cirrhosis (PBC), we genotyped 2426 PBC patients and 5731 unaffected controls from three independent cohorts using a single nucleotide polymorphism (SNP) array (Immunochip) enriched for autoimmune disease risk loci. Meta-analysis of the genotype data sets identified a novel disease-associated locus near the TNFSF11 gene at 13q14, provided evidence for association at six additional immune-related loci not previously implicated in PBC and confirmed associations at 19 of 22 established risk loci. Results of conditional analyses also provided evidence for multiple independent association signals at four risk loci, with haplotype analyses suggesting independent SNP effects at the 2q32 and 16p13 loci, but complex haplotype driven effects at the 3q25 and 6p21 loci. By imputing classical HLA alleles from this data set, four class II alleles independently contributing to the association signal from this region were identified. Imputation of genotypes at the non-HLA loci also provided additional associations, but none with stronger effects than the genotyped variants. An epistatic interaction between the IL12RB2 risk locus at 1p31and the IRF5 risk locus at 7q32 was also identified and suggests a complementary effect of these loci in predisposing to disease. These data expand the repertoire of genes with potential roles in PBC pathogenesis that need to be explored by follow-up biological studies. PMID:22936693

  16. ENVIRONMENTAL ANALYSIS BY AB INITIO QUANTUM MECHANICAL COMPUTATION AND GAS CHROMATOGRAPHY/FOURIER TRANSFORM INFRARED SPECTROMETRY.

    Computational chemistry, in conjunction with gas chromatography/mass spectrometry/Fourier transform infrared spectrometry (GC/MS/FT-IR), was used to tentatively identify seven tetrachlorobutadiene (TCBD) isomers detected in an environmental sample. Computation of the TCBD infrare...

  17. Post-factum detection of radiation treatment of meat and fish by means of DNA alterations identified by gas chromatography-mass spectrometry or pulsed-field gel electrophoresis

    Mayer, M.

    1994-01-01

    The doctoral thesis explains methods and experiments for post-factum detection of radiation-induced alterations of DNA. There are various manifestations of such alterations. Ionizing radiation can directly alter the bases and/or sugar component, or can indirectly induce DNA damage by way of forming water radicals. Both mechanisms result in base derivatives, released for some part from the DNA strand, or formed by alterations of the 2-deoxyribose, inducing strand breaks ( single and double strand breaks). The first part of the thesis explains the approach applying GC-MS for detection of radiation-induced base derivatives, using herring sperm DNA as a model DNA. Some typical types of base derivatives were identified (thymine glycol, 5-hydroxycytosine).Some base derivatives were also found in DNA samples derived from poultry meat. These base derivatives are known to be indicators of food processing with ionizing radiation, but surprisingly were also found in non-irradiated controls, although in minor amounts. The second part discusses the identification of strand breaks applying the pused-field gel electrophoresis. This method is capable of producing evidence that irradiation markedly enhances the short-chain DNA molecules as compared to non-irradiated controls. DNA molecules of a size of approx. 2.2 million base pairs are almost completely broken into short-chain fragments. The method reliably detects radiation treatments down to 1500 Gy, even if applied long ago. (orig./MG) [de

  18. Atomic mass spectrometry

    Sanz-Medel, A.

    1997-01-01

    The elemental inorganic analysis seems to be dominated today by techniques based on atomic spectrometry. After an evaluation of advantages and limitations of using mass analysers (ion detectors) versus conventional photomultipliers (photon detector) a brief review of the more popular techniques of the emerging Atomic Mass spectrometry is carried out. Their huge potential for inorganic trace analysis is such that in the future we could well witness how this end of the century and millennium marked the fall of the photons empire in Analytical Atomic Spectrometry. (Author)

  19. Multiple strategies to identify HIV-positive black men who have sex with men and transgender women in New York City: a cross-sectional analysis of recruitment results.

    Franks, Julie; Mannheimer, Sharon B; Hirsch-Moverman, Yael; Hayes-Larson, Eleanor; Colson, Paul W; Ortega, Hugo; El-Sadr, Wafaa M

    2018-03-01

    Black men who have sex with men and transgender women are at high risk for HIV infection, but are more likely to be unaware of their infection or not in care for diagnosed HIV compared to other races. Respondent driven sampling has been advanced as a method to reach stigmatized and hidden populations for HIV testing. We compared strategies to recruit black, substance-using men who have sex with men and transgender women to identify newly diagnosed HIV infection, or those previously diagnosed but not in care. The STAR (Seek, Test, and Retain) study (ClinicalTrials.gov NCT01790360) used several recruitment strategies to identify black, substance-using men who have sex with men and transgender women with undiagnosed HIV infection or with previously diagnosed HIV infection but who were not in HIV care. Respondent-driven sampling, community-based recruitment and online advertising were used to recruit participants. Incentivized peer referral was integrated into all recruitment strategies. Participants completed interviewer-administered questionnaires and HIV testing. Demographic and HIV risk-related characteristics and recruitment strategy were summarized and stratified by HIV status. Associations were tested using Pearson's chi-squared, Fisher's exact, and Wilcoxon rank sum tests. Factors associated with HIV-positive diagnosis at p recruitment strategies, respondent driven sampling was least effective in identifying HIV-positive participants. Integrating multiple recruitment strategies yielded a large sample of black men who have sex with men and transgender women at substantial risk for HIV. Respondent-driven sampling was less effective than other strategies at identifying men who have sex with men and transgender women with HIV. © 2018 The Authors. Journal of the International AIDS Society published by John Wiley & sons Ltd on behalf of the International AIDS Society.

  20. Software for nuclear spectrometry

    1998-10-01

    The Advisory Group Meeting (AGM) on Software for Nuclear Spectrometry was dedicated to review the present status of software for nuclear spectrometry and to advise on future activities in this field. Because similar AGM and consultant's meetings had been held in the past; together with an attempt to get more streamlined, this AGM was devoted to the specific field of software for gamma ray spectrometry. Nevertheless, many of the issues discussed and the recommendations made are of general concern for any software on nuclear spectrometry. The report is organized by sections. The 'Summary' gives conclusions and recommendations adopted at the AGM. These conclusions and recommendations resulted from the discussions held during and after presentations of the scientific and technical papers. These papers are reported here in their integral form in the following Sections

  1. Tandem mass spectrometry at low kinetic energy

    Cooks, R.G.; Hand, O.W.

    1987-01-01

    Recent progress in mass spectrometry, as applied to molecular analysis, is reviewed with emphasis on tandem mass spectrometry. Tandem instruments use multiple analyzers (sector magnets, quadrupole mass filters and time-of-flight devices) to select particular molecules in ionic form, react them in the gas-phase and then record the mass, momenta or kinetic energies of their products. The capabilities of tandem mass spectrometry for identification of individual molecules or particular classes of compounds in complex mixtures are illustrated. Several different types of experiments can be run using a tandem mass spectrometer; all share the feature of sifting the molecular mixture being analyzed on the basis of chemical properties expressed in terms of ionic mass, kinetic energy or charge state. Applications of mass spectrometry to biological problems often depend upon desorption methods of ionization in which samples are bombarded with particle beams. Evaporation of preformed charged species from the condensed phase into the vacuum is a particularly effective method of ionization. It is suggested that the use of accelerator mass spectrometers be extended to include problems of molecular analysis. In such experiments, low energy tandem mass spectrometry conducted in the eV or keV range of energies, would be followed by further characterization of the production ion beam using high selective MeV collision processes

  2. [Imaging Mass Spectrometry in Histopathologic Analysis].

    Yamazaki, Fumiyoshi; Seto, Mitsutoshi

    2015-04-01

    Matrix-assisted laser desorption/ionization (MALDI)-imaging mass spectrometry (IMS) enables visualization of the distribution of a range of biomolecules by integrating biochemical information from mass spectrometry with positional information from microscopy. IMS identifies a target molecule. In addition, IMS enables global analysis of biomolecules containing unknown molecules by detecting the ratio of the molecular weight to electric charge without any target, which makes it possible to identify novel molecules. IMS generates data on the distribution of lipids and small molecules in tissues, which is difficult to visualize with either conventional counter-staining or immunohistochemistry. In this review, we firstly introduce the principle of imaging mass spectrometry and recent advances in the sample preparation method. Secondly, we present findings regarding biological samples, especially pathological ones. Finally, we discuss the limitations and problems of the IMS technique and clinical application, such as in drug development.

  3. Glycomics using mass spectrometry

    Wuhrer, Manfred

    2013-01-01

    Mass spectrometry plays an increasingly important role in structural glycomics. This review provides an overview on currently used mass spectrometric approaches such as the characterization of glycans, the analysis of glycopeptides obtained by proteolytic cleavage of proteins and the analysis of glycosphingolipids. The given examples are demonstrating the application of mass spectrometry to study glycosylation changes associated with congenital disorders of glycosylation, lysosomal storage di...

  4. Ion mobility spectrometry

    Eiceman, GA

    2005-01-01

    Key Developments for Faster, More Precise Detection Capabilities Driven by the demand for the rapid and advanced detection of explosives, chemical and biological warfare agents, and narcotics, ion mobility spectrometry (IMS) undergone significant refinements in technology, computational capabilities, and understanding of the principles of gas phase ion chemistry and mobility. Beginning with a thorough discussion of the fundamental theories and physics of ion mobility, Ion Mobility Spectrometry, Second Edition describes the recent advances in instrumentation and newly

  5. Mass spectrometry and tandem mass spectrometry of citrus limonoids.

    Tian, Qingguo; Schwartz, Steven J

    2003-10-15

    Methods for atmospheric pressure chemical ionization tandem mass spectrometry (APCI-MS/MS) of citrus limonoid aglycones and electrospray ionization tandem mass spectrometry (ESI-MS/MS) of limonoid glucosides are reported. The fragmentation patterns of four citrus limonoid aglycones (limonin, nomilin, obacunone, and deacetylnomilin) and six limonoid glucosides, that is, limonin 17-beta-D-glucopyranoside (LG), nomilin 17-beta-D-glucopyranoside (NG), nomilinic acid 17-beta-D-glucopyranoside (NAG), deacetyl nomilinic acid 17-beta-D-glucopyranoside (DNAG), obacunone 17-beta-D-glucopyranoside (OG), and obacunoic acid 17-beta-D-glucopyranoside (OAG) were investigated using a quadruple mass spectrometer in low-energy collisionally activated dissociation (CAD). The four limonoid aglycones and four limonoid glucosides (LG, OG, NAG, and DNAG) were purified from citrus seeds; the other two limonoid glucosides (NG and OAG) were tentatively identified in the crude extract of grapefruit seeds by ESI mass spectrometry in both positive and negative ion analysis. Ammonium hydroxide or acetic acid was added to the mobile phase to facilitate ionization. During positive ion APCI analysis of limonoid aglycones, protonated molecular ion, [M + H]+, or adduct ion, [M + NH3 + H]-, was formed as base peaks when ammonium hydroxide was added to the mobile phase. Molecular anions or adduct ions with acetic acid ([M + HOAc - H] and [M + HOAc]-) or a deprotonated molecular ion were produced during negative ion APCI analysis of limonoid aglycones, depending on the mobile-phase modifier used. Positive ion ESI-MS of limonoid glucosides produced adduct ions of [M + H + NH3]+, [M + Na]+, and [M + K]+ when ammonium hydroxide was added to the mobile phase. After collisionally activated dissociation (CAD) of the limonoid aglycone molecular ions in negative ion APCI analysis, fragment ions indicated structural information of the precursor ions, showing the presence of methyl, carboxyl, and oxygenated ring

  6. Determination of albendazole sulfoxide in human plasma by using liquid chromatography-tandem mass spectrometry.

    Saraner, Nihal; Özkan, Güler Yağmur; Güney, Berrak; Alkan, Erkin; Burul-Bozkurt, Nihan; Sağlam, Onursal; Fikirdeşici, Ezgi; Yıldırım, Mevlüt

    2016-06-01

    A rapid, simple and sensitive method was developed and validated using liquid chromatography-tandem mass spectrometry (LC-MS/MS) for determination of albendazole sulfoxide (ABZOX) in human plasma. The plasma samples were extracted by protein precipitation using albendazole sulfoxide-d3 as internal standard (IS). The chromatographic separation was performed on Waters Xbridge C18Column (100×4.6mm, 3.5μm) with a mobile phase consisting of ammonia solution, water and methanol at a flow rate of 0.70mL/min. ABZOX was detected and identified by mass spectrometry with electrospray ionization (ESI) in positive ion and multiple-reaction monitoring (MRM) mode. The method was linear in the range of 3-1500ng/mL for ABZOX. This method was successfully applied to the bioequivalence study in human plasma samples. Copyright © 2016 Elsevier B.V. All rights reserved.

  7. Acetonitrile Ion Suppression in Atmospheric Pressure Ionization Mass Spectrometry

    Colizza, Kevin; Mahoney, Keira E.; Yevdokimov, Alexander V.; Smith, James L.; Oxley, Jimmie C.

    2016-11-01

    Efforts to analyze trace levels of cyclic peroxides by liquid chromatography/mass spectrometry gave evidence that acetonitrile suppressed ion formation. Further investigations extended this discovery to ketones, linear peroxides, esters, and possibly many other types of compounds, including triazole and menadione. Direct ionization suppression caused by acetonitrile was observed for multiple adduct types in both electrospray ionization and atmospheric pressure chemical ionization. The addition of only 2% acetonitrile significantly decreased the sensitivity of analyte response. Efforts to identify the mechanism were made using various nitriles. The ion suppression was reduced by substitution of an acetonitrile hydrogen with an electron-withdrawing group, but was exacerbated by electron-donating or steric groups adjacent to the nitrile. Although current theory does not explain this phenomenon, we propose that polar interactions between the various functionalities and the nitrile may be forming neutral aggregates that manifest as ionization suppression.

  8. Mass Spectrometry to Identify New Biomarkers of Nerve Agent Exposure

    2008-04-01

    µL precipitant solution containing 25 -38% PEG 3350 , 50 mM potassium phosphate pH 7.0 and 100 mM ammonium acetate. Similar looking crystals were...also obtained when the precipitant solution contained 0.17 M ammonium sulfate, 85 mM MES pH 6.5, 26% PEG 5000MME and 15% glycerol. Identification of the...obtained by vapor diffusion in high PEG conditions that were previously reported for preparation of other human serum albumin crystals (Carter et al

  9. Mass Spectrometry to Identify New Biomarkers of Nerve Agent Exposure

    2010-04-01

    preparations. Improving thermal stability by mutagene- sis or by selecting enzyme candidates in an extremophile biotope, e.g. thermophilic bacteria [36...target for oganophosphorus agent (OP) binding to enzymes is the active site serine in the consensus sequence GlyXSerXGly of acetylcholinesterase. By...human plasma. Task 6. Use a second method, for example enzyme activity assays or immunoprecipitation, to confirm the identity of soman-labeled proteins

  10. Mass Spectrometry to Identify New Biomarkers of Nerve Agent Exposure

    2009-04-01

    calculations for class C beta- lactamases: the role of Tyr-150. Proteins 40:23-28. Lewis SD, Johnson FA and Shafer JA (1976) Potentiometric determination of...example, in the presence of a 2-fold excess of soman, 100% inactivation of the AAA activity of albumin was never reached. The titration plot (not shown... Titration of trans- ferrin with ferric ion was performed as described (Welch and Skinner, 1989). A 1 mg/ml solution of apo-human transferrin was

  11. Nanostructure-initiator mass spectrometry biometrics

    Leclerc, Marion; Bowen, Benjamin; Northen, Trent

    2015-09-08

    Several embodiments described herein are drawn to methods of identifying an analyte on a subject's skin, methods of generating a fingerprint, methods of determining a physiological change in a subject, methods of diagnosing health status of a subject, and assay systems for detecting an analyte and generating a fingerprint, by nanostructure-initiator mass spectrometry (NIMS).

  12. Lipidomic mass spectrometry and its application in neuroscience

    Mabel; Enriquez-Algeciras; Sanjoy; K; Bhattacharya

    2013-01-01

    Central and peripheral nervous systems are lipid rich tissues. Lipids, in the context of lipid-protein complexes, surround neurons and provide electrical insulation for transmission of signals allowing neurons to remain embedded within a conducting environment. Lipids play a key role in vesicle formation and fusion in synapses. They provide means of rapid signaling, cell motility and migration for astrocytes and other cell types that surround and play supporting roles neurons. Unlike many other signaling molecules, lipids are capable of multiple signaling events based on the different fragments generated from a single precursor during each event. Lipidomics, until recently suffered from two major disadvantages:(1) level of expertise required an overwhelming amount of chemical detail to correctly identify a vast number of different lipids which could be close in their chemical reactivity; and(2) high amount of purified compounds needed by analytical techniques to determine their structures. Advances in mass spectrometry have enabled overcoming these two limitations. Mass spectrometry offers a great degree of simplicity in identification and quantification of lipids directly extracted from complex biological mixtures. Mass spectrometers can be regarded to as mass analyzers. There are those that separate and analyze the product ion fragments in space(spatial) and those which separate product ions in time in the same space(temporal). Databases and standardized instrument parameters have further aided the capabilities of the spatial instruments while recent advances in bioinformatics have made the identification and quantification possible using temporal instruments.

  13. Forensic Mass Spectrometry

    Hoffmann, William D.; Jackson, Glen P.

    2015-07-01

    Developments in forensic mass spectrometry tend to follow, rather than lead, the developments in other disciplines. Examples of techniques having forensic potential born independently of forensic applications include ambient ionization, imaging mass spectrometry, isotope ratio mass spectrometry, portable mass spectrometers, and hyphenated chromatography-mass spectrometry instruments, to name a few. Forensic science has the potential to benefit enormously from developments that are funded by other means, if only the infrastructure and personnel existed to adopt, validate, and implement the new technologies into casework. Perhaps one unique area in which forensic science is at the cutting edge is in the area of chemometrics and the determination of likelihood ratios for the evaluation of the weight of evidence. Such statistical techniques have been developed most extensively for ignitable-liquid residue analyses and isotope ratio analysis. This review attempts to capture the trends, motivating forces, and likely impact of developing areas of forensic mass spectrometry, with the caveat that none of this research is likely to have any real impact in the forensic community unless: (a) The instruments developed are turned into robust black boxes with red and green lights for positives and negatives, respectively, or (b) there are PhD graduates in the workforce who can help adopt these sophisticated techniques.

  14. Novel method for the rapid and specific extraction of multiple β2 -agonist residues in food by tailor-made Monolith-MIPs extraction disks and detection by gas chromatography with mass spectrometry.

    Liu, Haibo; Gan, Ning; Chen, Yinji; Ding, Qingqing; Huang, Jie; Lin, Saichai; Cao, Yuting; Li, Tianhua

    2016-09-01

    A quick and specific pretreatment method based on a series of extraction clean-up disks, consisting of molecularly imprinted polymer monoliths and C18 adsorbent, was developed for the specific enrichment of salbutamol and clenbuterol residues in food. The molecularly imprinted monolithic polymer disk was synthesized using salbutamol as a template through a one-step synthesis process. It can simultaneously and specifically recognize salbutamol and clenbuterol. The monolithic polymer disk and series of C18 disks were assembled with a syringe to form a set of tailor-made devices for the extraction of target molecules. In a single run, salbutamol and clenbuterol can be specifically extracted, cleaned, and eluted by methanol/acetic acid/H2 O. The target molecules, after a silylation derivatization reaction were detected by gas chromatography-mass spectrometry. The parameters including solvent desorption, sample pH, and the cycles of reloading were investigated and discussed. Under the optimized extraction and clean-up conditions, the limits of detection and quantitation were determined as 0.018-0.022 and 0.042-0.049 ng/g for salbutamol and clenbuterol, respectively. The assay described was convenient, rapid, and specific; thereby potentially efficient in the high-throughput analysis of β2 -agonists residues in real food samples. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  15. Fourier Transform Mass Spectrometry

    Scigelova, Michaela; Hornshaw, Martin; Giannakopulos, Anastassios; Makarov, Alexander

    2011-01-01

    This article provides an introduction to Fourier transform-based mass spectrometry. The key performance characteristics of Fourier transform-based mass spectrometry, mass accuracy and resolution, are presented in the view of how they impact the interpretation of measurements in proteomic applications. The theory and principles of operation of two types of mass analyzer, Fourier transform ion cyclotron resonance and Orbitrap, are described. Major benefits as well as limitations of Fourier transform-based mass spectrometry technology are discussed in the context of practical sample analysis, and illustrated with examples included as figures in this text and in the accompanying slide set. Comparisons highlighting the performance differences between the two mass analyzers are made where deemed useful in assisting the user with choosing the most appropriate technology for an application. Recent developments of these high-performing mass spectrometers are mentioned to provide a future outlook. PMID:21742802

  16. Mass spectrometry: a revolution in clinical microbiology?

    Lavigne, Jean-Philippe; Espinal, Paula; Dunyach-Remy, Catherine; Messad, Nourredine; Pantel, Alix; Sotto, Albert

    2013-02-01

    Recently, different bacteriological laboratory interventions that decrease reporting time have been developed. These promising new broad-based techniques have merit, based on their ability to identify rapidly many bacteria, organisms difficult to grow or newly emerging strains, as well as their capacity to track disease transmission. The benefit of rapid reporting of identification and/or resistance of bacteria can greatly impact patient outcomes, with an improvement in the use of antibiotics, in the reduction of the emergence of multidrug resistant bacteria and in mortality rates. Different techniques revolve around mass spectrometry (MS) technology: matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS), PCR combined with electrospray ionization-mass spectrometry (PCR/ESIMS), iPLEX MassArray system and other new evolutions combining different techniques. This report emphasizes the (r)evolution of these technologies in clinical microbiology.

  17. Ambient ionization mass spectrometry

    Lebedev, A T

    2015-01-01

    Ambient ionization mass spectrometry emerged as a new scientific discipline only about ten years ago. A considerable body of information has been reported since that time. Keeping the sensitivity, performance and informativity of classical mass spectrometry methods, the new approach made it possible to eliminate laborious sample preparation procedures and triggered the development of miniaturized instruments to work directly in the field. The review concerns the theoretical foundations and design of ambient ionization methods. Their advantages and drawbacks, as well as prospects for application in chemistry, biology, medicine, environmetal analysis, etc., are discussed. The bibliography includes 194 references

  18. RadNet Real-Time Monitoring Spectrometry Data Inventory

    U.S. Environmental Protection Agency — The RadNet Real-Time Monitoring Spectrometry Data Inventory contains measured data used to identify and measure specific radioactive materials in the atmosphere at...

  19. Mass spectrometry in nuclear science and technology

    Komori, Takuji

    1985-01-01

    Mass spectrometry has been widely used and playing a very important role in the field of nuclear science and technology. A major reason for this is that not only the types of element but also its isotopes have to be identified and measured in this field. Thus, some applications of this analytical method are reviewed and discussed in this article. Its application to analytical chemistry is described in the second section following an introductory section, which includes subsections for isotropic dilution mass spectrometry, resonance ionization mass spectrometry and isotopic correlation technique. The isotopic ratio measurement for hydrogen, uranium and plutonium as well as nuclear material control and safeguards are also reviewed in this section. In the third section, mass spectrometry is discussed in relation to nuclear reactors, with subsections on natural uranium reactor and neutron flux observation. Some techniques for measuring the burnup fraction, including the heavy isotopic ratio method and fission product monitoring, are also described. In the fourth section, application of mass spectrometry to measurement of nuclear constants, such as ratio of effective cross-sectional area for 235 U, half-life and fission yield is reviewed. (Nogami, K.)

  20. Identification of Vitamin D3 Oxidation Products Using High-Resolution and Tandem Mass Spectrometry

    Mahmoodani, Fatemeh; Perera, Conrad O.; Abernethy, Grant; Fedrizzi, Bruno; Greenwood, David; Chen, Hong

    2018-03-01

    In a successful fortification program, the stability of micronutrients added to the food is one of the most important factors. The added vitamin D3 is known to sometimes decline during storage of fortified milks, and oxidation through fatty acid lipoxidation could be suspected as the likely cause. Identification of vitamin D3 oxidation products (VDOPs) in natural foods is a challenge due to the low amount of their contents and their possible transformation to other compounds during analysis. The main objective of this study was to find a method to extract VDOPs in simulated whole milk powder and to identify these products using LTQ-ion trap, Q-Exactive Orbitrap and triple quadrupole mass spectrometry. The multistage mass spectrometry (MSn) spectra can help to propose plausible schemes for unknown compounds and their fragmentations. With the growth of combinatorial libraries, mass spectrometry (MS) has become an important analytical technique because of its speed of analysis, sensitivity, and accuracy. This study was focused on identifying the fragmentation rules for some VDOPs by incorporating MS data with in silico calculated MS fragmentation pathways. Diels-Alder derivatization was used to enhance the sensitivity and selectivity for the VDOPs' identification. Finally, the confirmed PTAD-derivatized target compounds were separated and analyzed using ESI(+)-UHPLC-MS/MS in multiple reaction monitoring (MRM) mode. [Figure not available: see fulltext.

  1. Miniaturization and Mass Spectrometry

    le Gac, S.; le Gac, Severine; van den Berg, Albert; van den Berg, A.; Unknown, [Unknown

    2009-01-01

    With this book we want to illustrate how two quickly growing fields of instrumentation and technology, both applied to life sciences, mass spectrometry and microfluidics (or microfabrication) naturally came to meet at the end of the last century and how this marriage impacts on several types of

  2. Fourier Transform Mass Spectrometry.

    Gross, Michael L.; Rempel, Don L.

    1984-01-01

    Discusses the nature of Fourier transform mass spectrometry and its unique combination of high mass resolution, high upper mass limit, and multichannel advantage. Examines its operation, capabilities and limitations, applications (ion storage, ion manipulation, ion chemistry), and future applications and developments. (JN)

  3. Analytical mass spectrometry

    1990-01-01

    This 43rd Annual Summer Symposium on Analytical Chemistry was held July 24--27, 1990 at Oak Ridge, TN and contained sessions on the following topics: Fundamentals of Analytical Mass Spectrometry (MS), MS in the National Laboratories, Lasers and Fourier Transform Methods, Future of MS, New Ionization and LC/MS Methods, and an extra session. (WET)

  4. Analytical mass spectrometry. Abstracts

    1990-12-31

    This 43rd Annual Summer Symposium on Analytical Chemistry was held July 24--27, 1990 at Oak Ridge, TN and contained sessions on the following topics: Fundamentals of Analytical Mass Spectrometry (MS), MS in the National Laboratories, Lasers and Fourier Transform Methods, Future of MS, New Ionization and LC/MS Methods, and an extra session. (WET)

  5. Characterizing the lipid and metabolite changes associated with placental function and pregnancy complications using ion mobility spectrometry-mass spectrometry and mass spectrometry imaging

    Burnum-Johnson, Kristin E.; Baker, Erin S.; Metz, Thomas O.

    2017-12-01

    Successful pregnancy is dependent upon discrete biological events, which include embryo implantation, decidualization, and placentation. Problems associated with each of these events can cause infertility or conditions such as preeclampsia. A greater understanding of the molecular changes associated with these complex processes is necessary to aid in identifying treatments for each condition. Previous nuclear magnetic resonance spectroscopy and mass spectrometry studies have been used to identify metabolites and lipids associated with pregnancy-related complications. However, due to limitations associated with conventional implementations of both techniques, novel technology developments are needed to more fully understand the initiation and development of pregnancy related problems at the molecular level. In this perspective, we describe current analytical techniques for metabolomic and lipidomic characterization of pregnancy complications and discuss the potential for new technologies such as ion mobility spectrometry-mass spectrometry and mass spectrometry imaging to contribute to a better understanding of the molecular changes that affect the placenta and pregnancy outcomes.

  6. Development of a highly sensitive methodology for quantitative determination of fexofenadine in a microdose study by multiple injection method using ultra-high performance liquid chromatography with tandem mass spectrometry.

    Tanaka, Yukari; Yoshikawa, Yutaka; Yasui, Hiroyuki

    2012-01-01

    An ultra high-sensitivity method for quantifying fexofenadine concentration in rat plasma samples by multiple injection method (MIM) was developed for a microdose study. In this study, MIM involved continuous injections of multiple samples containing the single compound into a column of the ultra-HPLC (UHPLC) system, and then, temporary trapping of the analyte at the column head. This was followed by elution of the compound from the column and detection by mass spectrometer. Fexofenadine, used as a model compound in this study, was extracted from the plasma samples by a protein precipitation method. Chromatographic separation was achieved on a reversed-phase C18 column by using a gradient method with 0.1% formic acid and 0.1% formic acid in acetonitrile as the mobile phase. The analyte was quantified in the positive-ion electrospray ionization mode using selected reaction monitoring. In this study, the analytical time per fexofenadine sample was approximately 2 min according to the UHPLC system. The method exhibited the linear dynamic ranges of 5-5000 pg/mL for fexofenadine in rat plasma. The intra-day precisions were from 3.2 to 8.7% and the accuracy range was 95.2-99.3%. The inter-day precisions and accuracies ranged from 3.5 to 8.4% and from 98.6 to 102.6%, respectively. The validated MIM was successfully applied to a microdose study in the rats that received oral administration of 100 µg/kg fexofenadine. We suggest that this method might be beneficial for the quantification of fexofenadine concentrations in a microdose clinical study.

  7. Mass Spectrometry and Antibody-Based Characterization of Blood Vessels from Brachylophosaurus canadensis.

    Cleland, Timothy P; Schroeter, Elena R; Zamdborg, Leonid; Zheng, Wenxia; Lee, Ji Eun; Tran, John C; Bern, Marshall; Duncan, Michael B; Lebleu, Valerie S; Ahlf, Dorothy R; Thomas, Paul M; Kalluri, Raghu; Kelleher, Neil L; Schweitzer, Mary H

    2015-12-04

    Structures similar to blood vessels in location, morphology, flexibility, and transparency have been recovered after demineralization of multiple dinosaur cortical bone fragments from multiple specimens, some of which are as old as 80 Ma. These structures were hypothesized to be either endogenous to the bone (i.e., of vascular origin) or the result of biofilm colonizing the empty osteonal network after degradation of original organic components. Here, we test the hypothesis that these structures are endogenous and thus retain proteins in common with extant archosaur blood vessels that can be detected with high-resolution mass spectrometry and confirmed by immunofluorescence. Two lines of evidence support this hypothesis. First, peptide sequencing of Brachylophosaurus canadensis blood vessel extracts is consistent with peptides comprising extant archosaurian blood vessels and is not consistent with a bacterial, cellular slime mold, or fungal origin. Second, proteins identified by mass spectrometry can be localized to the tissues using antibodies specific to these proteins, validating their identity. Data are available via ProteomeXchange with identifier PXD001738.

  8. Mass spectrometry in oceanography

    Aggarwal, Suresh K.

    2000-01-01

    Mass spectrometry plays an important role in oceanography for various applications. Different types of inorganic as well as organic mass spectrometric techniques are being exploited world-wide to understand the different aspects of marine science, for palaeogeography, palaeoclimatology and palaeoecology, for isotopic composition and concentrations of different elements as well as for speciation studies. The present paper reviews some of the applications of atomic mass spectrometric techniques in the area of oceanography

  9. Hydrogen Exchange Mass Spectrometry

    Mayne, Leland

    2018-01-01

    Hydrogen exchange (HX) methods can reveal much about the structure, energetics, and dynamics of proteins. The addition of mass spectrometry (MS) to an earlier fragmentation-separation HX analysis now extends HX studies to larger proteins at high structural resolution and can provide information not available before. This chapter discusses experimental aspects of HX labeling, especially with respect to the use of MS and the analysis of MS data. PMID:26791986

  10. Development of an on-line flow injection Sr/matrix separation method for accurate, high-throughput determination of Sr isotope ratios by multiple collector-inductively coupled plasma-mass spectrometry.

    Galler, Patrick; Limbeck, Andreas; Boulyga, Sergei F; Stingeder, Gerhard; Hirata, Takafumi; Prohaska, Thomas

    2007-07-01

    This work introduces a newly developed on-line flow injection (FI) Sr/Rb separation method as an alternative to the common, manual Sr/matrix batch separation procedure, since total analysis time is often limited by sample preparation despite the fast rate of data acquisition possible by inductively coupled plasma-mass spectrometers (ICPMS). Separation columns containing approximately 100 muL of Sr-specific resin were used for on-line FI Sr/matrix separation with subsequent determination of (87)Sr/(86)Sr isotope ratios by multiple collector ICPMS. The occurrence of memory effects exhibited by the Sr-specific resin, a major restriction to the repetitive use of this costly material, could successfully be overcome. The method was fully validated by means of certified reference materials. A set of two biological and six geological Sr- and Rb-bearing samples was successfully characterized for its (87)Sr/(86)Sr isotope ratios with precisions of 0.01-0.04% 2 RSD (n = 5-10). Based on our measurements we suggest (87)Sr/(86)Sr isotope ratios of 0.713 15 +/- 0.000 16 (2 SD) and 0.709 31 +/- 0.000 06 (2 SD) for the NIST SRM 1400 bone ash and the NIST SRM 1486 bone meal, respectively. Measured (87)Sr/(86)Sr isotope ratios for five basalt samples are in excellent agreement with published data with deviations from the published value ranging from 0 to 0.03%. A mica sample with a Rb/Sr ratio of approximately 1 was successfully characterized for its (87)Sr/(86)Sr isotope signature to be 0.718 24 +/- 0.000 29 (2 SD) by the proposed method. Synthetic samples with Rb/Sr ratios of up to 10/1 could successfully be measured without significant interferences on mass 87, which would otherwise bias the accuracy and uncertainty of the obtained data.

  11. Determination of 5-fluorouracil in plasma with HPLC-tandem mass spectrometry

    van Kuilenburg, A. B. P.; van Lenthe, H.; Maring, J. G.; van Gennip, A. H.

    2006-01-01

    In this article, we describe a fast and specific method to measure 5FU with HPLC tandem-mass spectrometry. Reversed-phase HPLC was combined with electrospray ionization tandem mass spectrometry and detection was performed by multiple-reaction monitoring. Stable-isotope-labeled 5FU (1,3-15N2-5FU) was

  12. Quantitation of mycotoxins using direct analysis in real time (DART)-mass spectrometry (MS)

    Ambient ionization represents a new generation of mass spectrometry ion sources which is used for rapid ionization of small molecules under ambient conditions. The combination of ambient ionization and mass spectrometry allows analyzing multiple food samples with simple or no sample treatment, or in...

  13. Mass spectrometry with accelerators.

    Litherland, A E; Zhao, X-L; Kieser, W E

    2011-01-01

    As one in a series of articles on Canadian contributions to mass spectrometry, this review begins with an outline of the history of accelerator mass spectrometry (AMS), noting roles played by researchers at three Canadian AMS laboratories. After a description of the unique features of AMS, three examples, (14)C, (10)Be, and (129)I are given to illustrate the methods. The capabilities of mass spectrometry have been extended by the addition of atomic isobar selection, molecular isobar attenuation, further ion acceleration, followed by ion detection and ion identification at essentially zero dark current or ion flux. This has been accomplished by exploiting the techniques and accelerators of atomic and nuclear physics. In 1939, the first principles of AMS were established using a cyclotron. In 1977 the selection of isobars in the ion source was established when it was shown that the (14)N(-) ion was very unstable, or extremely difficult to create, making a tandem electrostatic accelerator highly suitable for assisting the mass spectrometric measurement of the rare long-lived radioactive isotope (14)C in the environment. This observation, together with the large attenuation of the molecular isobars (13)CH(-) and (12)CH 2(-) during tandem acceleration and the observed very low background contamination from the ion source, was found to facilitate the mass spectrometry of (14)C to at least a level of (14)C/C ~ 6 × 10(-16), the equivalent of a radiocarbon age of 60,000 years. Tandem Accelerator Mass Spectrometry, or AMS, has now made possible the accurate radiocarbon dating of milligram-sized carbon samples by ion counting as well as dating and tracing with many other long-lived radioactive isotopes such as (10)Be, (26)Al, (36)Cl, and (129)I. The difficulty of obtaining large anion currents with low electron affinities and the difficulties of isobar separation, especially for the heavier mass ions, has prompted the use of molecular anions and the search for alternative

  14. Simultaneous drug identification in urine of sexual assault victims by using liquid chromatography tandem mass spectrometry.

    Lee, Hei Hwa; Chen, Suen Chi; Lee, Jong Feng; Lin, Hsin Yu; Chen, Bai Hsiun

    2018-01-01

    According to domestic and international epidemiological investigation, the proportion of substance involved sexual assault has the trend of ascent. In the past, laboratory methods that investigated urine sample of the sexual assault victims was to screen with enzyme immunoassay and then confirmed with mass spectrometry. The objective of the study is to simultaneously identify abused drugs in 126 decoded urine samples of sexual assault victims by liquid chromatography tandem mass spectrometry. The instrument was operated in multiple-reaction monitoring with an electro-spray positive ionization mode. Chromatograms were separated with ACE5 C18 column on a gradient of acetonitrile. After liquid-liquid extraction, samples were passed through a 0.22μm PVDF filter before injection into the system. The limits of quantitation ranged from 0.2 to 10ng/mL. The precision (CV) results were below 12.9% (intraday) and 15.0% (interday). The intraday accuracy ranged from 84.8 to 121.0%, interday accuracy ranged from 72.0 to 117.3%. We found that 29 (23.0%) were positive for drugs. The most common drug identified is flunitrazepam (11.1%), followed by nimetazepam and ketamine (7.9%), some new psychoactive substances, such as 2C-B, mephedrone, methylone, PMA and PMMA were also identified. We identified abused drugs, benzodiazepines, and new psychoactive substances in urine of sexual assault victims by using liquid chromatography tandem mass spectrometry. Copyright © 2017 Elsevier B.V. All rights reserved.

  15. Automated, parallel mass spectrometry imaging and structural identification of lipids

    Ellis, Shane R.; Paine, Martin R.L.; Eijkel, Gert B.

    2018-01-01

    We report a method that enables automated data-dependent acquisition of lipid tandem mass spectrometry data in parallel with a high-resolution mass spectrometry imaging experiment. The method does not increase the total image acquisition time and is combined with automatic structural assignments....... This lipidome-per-pixel approach automatically identified and validated 104 unique molecular lipids and their spatial locations from rat cerebellar tissue....

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

    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...

  17. TG/DTG, FT-ICR Mass Spectrometry, and NMR Spectroscopy Study of Heavy Fuel Oil

    Elbaz, Ayman M.; Abdul Jameel, Abdul Gani; Hourani, Nadim; Emwas, Abdul-Hamid M.; Sarathy, Mani; Roberts, William L.

    2015-01-01

    infusion atmospheric pressure chemical ionization Fourier transform ion cyclotron resonance mass spectrometry (APCI-FTICR MS), high resolution 1H nuclear magnetic resonance (NMR), 13C NMR, and two-dimensional heteronuclear multiple bond correlation (HMBC

  18. Quantitation of multisite EGF receptor phosphorylation using mass spectrometry and a novel normalization approach

    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...

  19. On-Line Synthesis and Analysis by Mass Spectrometry

    Bain, Ryan M.; Pulliam, Christopher J.; Raab, Shannon A.; Cooks, R. Graham

    2015-01-01

    In this laboratory experiment, students learn how to use ESI to accelerate chemical synthesis and to couple it with on-line mass spectrometry for structural analysis. The Hantzsch synthesis of symmetric 1,4-dihydropyridines is a classic example of a one-pot reaction in which multiple intermediates can serve to indicate the progress of the reaction…

  20. Mass spectrometry in clinical chemistry

    Pettersen, J.E.

    1977-01-01

    A brief description is given of the functional elements of a mass spectrometer and of some currently employed mass spectrometric techniques, such as combined gas chromatography-mass spectrometry, mass chromatography, and selected ion monitoring. Various areas of application of mass spectrometry in clinical chemistry are discussed, such as inborn errors of metabolism and other metabolic disorders, intoxications, quantitative determinations of drugs, hormones, gases, and trace elements, and the use of isotope dilution mass spectrometry as a definitive method for the establishment of true values for concentrations of various compounds in reference sera. It is concluded that mass spectrometry is of great value in clinical chemistry. (Auth.)

  1. Sample Preprocessing For Atomic Spectrometry

    Kim, Sun Tae

    2004-08-01

    This book gives descriptions of atomic spectrometry, which deals with atomic absorption spectrometry such as Maxwell-Boltzmann equation and Beer-Lambert law, atomic absorption spectrometry for solvent extraction, HGAAS, ETASS, and CVAAS and inductively coupled plasma emission spectrometer, such as basic principle, generative principle of plasma and device and equipment, and interferences, and inductively coupled plasma mass spectrometry like device, pros and cons of ICP/MS, sample analysis, reagent, water, acid, flux, materials of experiments, sample and sampling and disassembling of sample and pollution and loss in open system and closed system.

  2. Multiple Perspectives / Multiple Readings

    Simon Biggs

    2005-01-01

    Full Text Available People experience things from their own physical point of view. What they see is usually a function of where they are and what physical attitude they adopt relative to the subject. With augmented vision (periscopes, mirrors, remote cameras, etc we are able to see things from places where we are not present. With time-shifting technologies, such as the video recorder, we can also see things from the past; a time and a place we may never have visited.In recent artistic work I have been exploring the implications of digital technology, interactivity and internet connectivity that allow people to not so much space/time-shift their visual experience of things but rather see what happens when everybody is simultaneously able to see what everybody else can see. This is extrapolated through the remote networking of sites that are actual installation spaces; where the physical movements of viewers in the space generate multiple perspectives, linked to other similar sites at remote locations or to other viewers entering the shared data-space through a web based version of the work.This text explores the processes involved in such a practice and reflects on related questions regarding the non-singularity of being and the sense of self as linked to time and place.

  3. Fourier transform ion cyclotron resonance mass spectrometry

    Marshall, Alan G.

    1998-06-01

    As for Fourier transform infrared (FT-IR) interferometry and nuclear magnetic resonance (NMR) spectroscopy, the introduction of pulsed Fourier transform techniques revolutionized ion cyclotron resonance mass spectrometry: increased speed (factor of 10,000), increased sensitivity (factor of 100), increased mass resolution (factor of 10,000-an improvement not shared by the introduction of FT techniques to IR or NMR spectroscopy), increased mass range (factor of 500), and automated operation. FT-ICR mass spectrometry is the most versatile technique for unscrambling and quantifying ion-molecule reaction kinetics and equilibria in the absence of solvent (i.e., the gas phase). In addition, FT-ICR MS has the following analytically important features: speed (~1 second per spectrum); ultrahigh mass resolution and ultrahigh mass accuracy for analysis of mixtures and polymers; attomole sensitivity; MSn with one spectrometer, including two-dimensional FT/FT-ICR/MS; positive and/or negative ions; multiple ion sources (especially MALDI and electrospray); biomolecular molecular weight and sequencing; LC/MS; and single-molecule detection up to 108 Dalton. Here, some basic features and recent developments of FT-ICR mass spectrometry are reviewed, with applications ranging from crude oil to molecular biology.

  4. SPARQL-enabled identifier conversion with Identifiers.org

    Wimalaratne, Sarala M.; Bolleman, Jerven; Juty, Nick; Katayama, Toshiaki; Dumontier, Michel; Redaschi, Nicole; Le Novère, Nicolas; Hermjakob, Henning; Laibe, Camille

    2015-01-01

    Motivation: On the semantic web, in life sciences in particular, data is often distributed via multiple resources. Each of these sources is likely to use their own International Resource Identifier for conceptually the same resource or database record. The lack of correspondence between identifiers introduces a barrier when executing federated SPARQL queries across life science data. Results: We introduce a novel SPARQL-based service to enable on-the-fly integration of life science data. This service uses the identifier patterns defined in the Identifiers.org Registry to generate a plurality of identifier variants, which can then be used to match source identifiers with target identifiers. We demonstrate the utility of this identifier integration approach by answering queries across major producers of life science Linked Data. Availability and implementation: The SPARQL-based identifier conversion service is available without restriction at http://identifiers.org/services/sparql. Contact: sarala@ebi.ac.uk PMID:25638809

  5. SPARQL-enabled identifier conversion with Identifiers.org.

    Wimalaratne, Sarala M; Bolleman, Jerven; Juty, Nick; Katayama, Toshiaki; Dumontier, Michel; Redaschi, Nicole; Le Novère, Nicolas; Hermjakob, Henning; Laibe, Camille

    2015-06-01

    On the semantic web, in life sciences in particular, data is often distributed via multiple resources. Each of these sources is likely to use their own International Resource Identifier for conceptually the same resource or database record. The lack of correspondence between identifiers introduces a barrier when executing federated SPARQL queries across life science data. We introduce a novel SPARQL-based service to enable on-the-fly integration of life science data. This service uses the identifier patterns defined in the Identifiers.org Registry to generate a plurality of identifier variants, which can then be used to match source identifiers with target identifiers. We demonstrate the utility of this identifier integration approach by answering queries across major producers of life science Linked Data. The SPARQL-based identifier conversion service is available without restriction at http://identifiers.org/services/sparql. © The Author 2015. Published by Oxford University Press.

  6. Alpha spectrometry and secondary ion mass spectrometry of thorium

    Strisovska, Jana; Kuruc, Jozef; Galanda, Dusan; Matel, Lubomir; Velic, Dusan; Aranyosiova, Monika

    2009-01-01

    A sample of thorium content on steel discs was prepared by electrodeposition with a view to determining the natural thorium isotope. Thorium was determined by alpha spectrometry and by secondary ion mass spectrometry and the results of the two methods were compared

  7. Nanoscience, nanotechnology and spectrometry

    Adams, Freddy C.; Barbante, Carlo

    2013-01-01

    Nanoscience has outgrown its infancy, and nanotechnology has found important applications in our daily life — with many more to come. Although the central concepts of the nano world, namely the changes of particular physical properties on the length scale of individual atoms and molecules, have been known and developed for quite some time already, experimental advances since the 1980s and recognition of the potential of nanomaterials led to a genuine breakthrough of the inherently multidisciplinary nanoscience field. Analytical nanoscience and nanotechnology and especially the use of micro and nano electro mechanical systems, of the quantum dots and of mass spectrometry, currently provide one of the most promising avenues for developments in analytical science, derived from their two main fields of action, namely (a) the analysis of nano-structured materials and (b) their use as new tools for analysis. An overview is given of recent developments and trends in the field, highlighting the importance and point out future directions, while also touching drawbacks, such as emerging concerns about health and environmental issues. - Highlights: • We review the analysis of nano-structured materials. • Nano-structured materials can be used as new tools for analysis. • Use of nano electro mechanical systems, of quantum dots and of mass spectrometry • Nanotechnologies are among the most promising tools in analytical science

  8. Nanoscience, nanotechnology and spectrometry

    Adams, Freddy C. [Department of Chemistry, University of Antwerp, B-2610 Wilrijk (Belgium); Barbante, Carlo, E-mail: barbante@unive.it [Institute for the Dynamics of Environmental Processes — CNR, Venice (Italy); Department of Environmental Sciences, Informatics and Statistics, Ca' Foscari University, Venice (Italy)

    2013-08-01

    Nanoscience has outgrown its infancy, and nanotechnology has found important applications in our daily life — with many more to come. Although the central concepts of the nano world, namely the changes of particular physical properties on the length scale of individual atoms and molecules, have been known and developed for quite some time already, experimental advances since the 1980s and recognition of the potential of nanomaterials led to a genuine breakthrough of the inherently multidisciplinary nanoscience field. Analytical nanoscience and nanotechnology and especially the use of micro and nano electro mechanical systems, of the quantum dots and of mass spectrometry, currently provide one of the most promising avenues for developments in analytical science, derived from their two main fields of action, namely (a) the analysis of nano-structured materials and (b) their use as new tools for analysis. An overview is given of recent developments and trends in the field, highlighting the importance and point out future directions, while also touching drawbacks, such as emerging concerns about health and environmental issues. - Highlights: • We review the analysis of nano-structured materials. • Nano-structured materials can be used as new tools for analysis. • Use of nano electro mechanical systems, of quantum dots and of mass spectrometry • Nanotechnologies are among the most promising tools in analytical science.

  9. A mass spectrometry proteomics data management platform.

    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/.

  10. Preface Miniaturization and Mass Spectrometry

    Unknown, [Unknown; le Gac, Severine; le Gac, S.; van den Berg, Albert; van den Berg, A.

    2009-01-01

    Miniaturization and Mass Spectrometry illustrates this trend and focuses on one particular analysis technique, mass spectrometry whose popularity has "dramatically" increased in the last two decades with the explosion of the field of biological analysis and the development of two "soft" ionization

  11. Negative chemical ionization mass spectrometry

    Smit, A.L.C.

    1979-01-01

    This thesis describes some aspects of Negative Chemical Ionization (NCI) mass spectrometry. The reasons for the growing interest in NCI are: (i) to extend the basic knowledge of negative ions and their reactions in the gas phase; (ii) to investigate whether or not this knowledge of negative ions can be used successfully to elucidate the structure of molecules by mass spectrometry. (Auth.)

  12. Laboratory of acceleration mass spectrometry

    Hybler, P.; Chrapan, J.

    2002-01-01

    In this paper authors describe the principle of the method of acceleration mass spectrometry and the construction plans of this instrument at the Faculty of ecology and environmental sciences in Banska Stiavnica. Using of this instrument for radiocarbon dating is discussed. A review of laboratories with acceleration mass spectrometry is presented

  13. Accelerator-based ultrasensitive mass spectrometry

    Gove, H.E.

    1985-01-01

    This chapter describes a new mass spectrometry technique involving charged particle accelerators normally used for basic research in nuclear science. Topics considered include the limitations of conventional mass spectrometry, the limitations of the direct measurement of radioactive decay, mass spectrometry using a tandem electrostatic accelerator, mass spectrometry using a cyclotron, how accelerator mass spectrometry circumvents the limitations of conventional mass spectrometry, measurements of stable isotopes, nuclear physics and astrophysics applications, modifications to existing accelerators, descriptions of dedicated systems, and future applications

  14. Multiple sclerosis

    ... indwelling catheter Osteoporosis or thinning of the bones Pressure sores Side effects of medicines used to treat the ... Daily bowel care program Multiple sclerosis - discharge Preventing pressure ulcers Swallowing problems Images Multiple sclerosis MRI of the ...

  15. MULTIPLE OBJECTS

    A. A. Bosov

    2015-04-01

    Full Text Available Purpose. The development of complicated techniques of production and management processes, information systems, computer science, applied objects of systems theory and others requires improvement of mathematical methods, new approaches for researches of application systems. And the variety and diversity of subject systems makes necessary the development of a model that generalizes the classical sets and their development – sets of sets. Multiple objects unlike sets are constructed by multiple structures and represented by the structure and content. The aim of the work is the analysis of multiple structures, generating multiple objects, the further development of operations on these objects in application systems. Methodology. To achieve the objectives of the researches, the structure of multiple objects represents as constructive trio, consisting of media, signatures and axiomatic. Multiple object is determined by the structure and content, as well as represented by hybrid superposition, composed of sets, multi-sets, ordered sets (lists and heterogeneous sets (sequences, corteges. Findings. In this paper we study the properties and characteristics of the components of hybrid multiple objects of complex systems, proposed assessments of their complexity, shown the rules of internal and external operations on objects of implementation. We introduce the relation of arbitrary order over multiple objects, we define the description of functions and display on objects of multiple structures. Originality.In this paper we consider the development of multiple structures, generating multiple objects.Practical value. The transition from the abstract to the subject of multiple structures requires the transformation of the system and multiple objects. Transformation involves three successive stages: specification (binding to the domain, interpretation (multiple sites and particularization (goals. The proposed describe systems approach based on hybrid sets

  16. Atomic fluorescence spectrometry with the inductively coupled plasma

    Omenetto, N.; Winefordner, J.D.

    1987-01-01

    Atomic fluorescence spectrometry (AFS) is based on the radiational activation of atoms and ions produced in a suitable atomizer (ionizer) and the subsequent measurement of the resulting radiational deactivation, called fluorescence. Atomic fluorescence spectrometry has been of considerable interest to researchers in atomic spectrometry because of its use for both analytical and diagnostic purposes. Unfortunately, the analytical applications of AFS have suffered from the lack of commercial instrumentation until the recent marketing of the Baird multiple-element, hollow cathode lamp-excited inductively coupled plasma system. This chapter is concerned strictly with the use of the inductively coupled plasma (ICP) as a cell and as a source for AFS. Many of the major references concerning the ICP in analytical AFS are categorized in Table 9.1, along with several reviews and diagnostical studies. For more detailed discussions of the fundamental aspects of AFS, the reader is referred to previous reviews

  17. Neutron spectrometry for reactor applications: status, limitations, and future directions

    Gold, R.

    1975-08-01

    The ability of ''state-of-the-art'' reactor neutron spectrometry to provide definitive environmental results required for high fluence radiation damage experiments is reviewed. A formal definition of the neutron component is presented as well as general considerations which accrue from both this definition and the existence of the mixed radiation field generally encountered in reactors. A description of four selected methods of reactor neutron spectrometry is included, namely Proton Recoil (PR) methods, Time-Of-Flight (TOF) methods, the 6 Li(n,α) 3 H coincidence method, and Multiple Foil Activation (MFA) methods. These selected methods are compared. Future requirements and directions for reactor neutron spectrometry are discussed. In particular, the needs of future CTR research are stressed and the He 4 - recoil proportional counter spectroscopy method is advanced as a means of meeting these future requirements. 50 references. (auth)

  18. A de novo 1.58 Mb deletion, including MAP2K6 and mapping 1.28 Mb upstream to SOX9, identified in a patient with Pierre Robin sequence and osteopenia with multiple fractures.

    Smyk, Marta; Roeder, Elizabeth; Cheung, Sau Wai; Szafranski, Przemyslaw; Stankiewicz, Paweł

    2015-08-01

    Defects of long-range regulatory elements of dosage-sensitive genes represent an under-recognized mechanism underlying genetic diseases. Haploinsufficiency of SOX9, the gene essential for development of testes and differentiation of chondrocytes, results in campomelic dysplasia, a skeletal malformation syndrome often associated with sex reversal. Chromosomal rearrangements with breakpoints mapping up to 1.6 Mb up- and downstream to SOX9, and disrupting its distant cis-regulatory elements, have been described in patients with milder forms of campomelic dysplasia, Pierre Robin sequence, and sex reversal. We present an ∼1.58 Mb deletion mapping ∼1.28 Mb upstream to SOX9 that encompasses its putative long-range cis-regulatory element(s) and MAP2K6 in a patient with Pierre Robin sequence and osteopenia with multiple fractures. Low bone mass panel testing using massively parallel sequencing of 23 nuclear genes, including COL1A1 and COL1A2 was negative. Based on the previous mouse model of Map2k6, suggesting that Sox9 is likely a downstream target of the p38 MAPK pathway, and our previous chromosome conformation capture-on-chip (4C) data showing potential interactions between SOX9 promoter and MAP2K6, we hypothesize that deletion of MAP2K6 might have affected SOX9 expression and contributed to our patient's phenotype. © 2015 Wiley Periodicals, Inc.

  19. DETECTING LOW-LEVEL SYNTHESIS IMPURITIES IN MODIFIED PHOSPHOROTHIOATE OLIGONUCLEOTIDES USING LIQUID CHROMATOGRAPHY – HIGH RESOLUTION MASS SPECTROMETRY

    Nikcevic, Irena; Wyrzykiewicz, Tadeusz K.; Limbach, Patrick A.

    2010-01-01

    Summary An LC-MS method based on the use of high resolution Fourier transform ion cyclotron resonance mass spectrometry (FTIRCMS) for profiling oligonucleotides synthesis impurities is described. Oligonucleotide phosphorothioatediesters (phosphorothioate oligonucleotides), in which one of the non-bridging oxygen atoms at each phosphorus center is replaced by a sulfur atom, are now one of the most popular oligonucleotide modifications due to their ease of chemical synthesis and advantageous pharmacokinetic properties. Despite significant progress in the solid-phase oligomerization chemistry used in the manufacturing of these oligonucleotides, multiple classes of low-level impurities always accompany synthetic oligonucleotides. Liquid chromatography-mass spectrometry has emerged as a powerful technique for the identification of these synthesis impurities. However, impurity profiling, where the entire complement of low-level synthetic impurities is identified in a single analysis, is more challenging. Here we present an LC-MS method based the use of high resolution-mass spectrometry, specifically Fourier transform ion cyclotron resonance mass spectrometry (FTIRCMS or FTMS). The optimal LC-FTMS conditions, including the stationary phase and mobile phases for the separation and identification of phosphorothioate oligonucleotides, were found. The characteristics of FTMS enable charge state determination from single m/z values of low-level impurities. Charge state information then enables more accurate modeling of the detected isotopic distribution for identification of the chemical composition of the detected impurity. Using this approach, a number of phosphorothioate impurities can be detected by LC-FTMS including failure sequences carrying 3′-terminal phosphate monoester and 3′-terminal phosphorothioate monoester, incomplete backbone sulfurization and desulfurization products, high molecular weight impurities, and chloral, isobutyryl, and N3 (2-cyanoethyl) adducts

  20. Coupling Front-End Separations, Ion Mobility Spectrometry, and Mass Spectrometry For Enhanced Multidimensional Biological and Environmental Analyses

    Zheng, Xueyun; Wojcik, Roza; Zhang, Xing; Ibrahim, Yehia M.; Burnum-Johnson, Kristin E.; Orton, Daniel J.; Monroe, Matthew E.; Moore, Ronald J.; Smith, Richard D.; Baker, Erin S.

    2017-01-01

    Ion mobility spectrometry (IMS) is a widely used analytical technique for rapid molecular separations in the gas phase. Though IMS alone is useful, its coupling with mass spectrometry (MS) and front-end separations is extremely beneficial for increasing measurement sensitivity, peak capacity of complex mixtures, and the scope of molecular information available from biological and environmental sample analyses. In fact, multiple disease screening and environmental evaluations have illustrated that the IMS-based multidimensional separations extract information that cannot be acquired with each technique individually. This review highlights three-dimensional separations using IMS-MS in conjunction with a range of front-end techniques, such as gas chromatography, supercritical fluid chromatography, liquid chromatography, solid-phase extractions, capillary electrophoresis, field asymmetric ion mobility spectrometry, and microfluidic devices. The origination, current state, various applications, and future capabilities of these multidimensional approaches are described in detail to provide insight into their uses and benefits. PMID:28301728

  1. Coupling Front-End Separations, Ion Mobility Spectrometry, and Mass Spectrometry For Enhanced Multidimensional Biological and Environmental Analyses

    Zheng, Xueyun; Wojcik, Roza; Zhang, Xing; Ibrahim, Yehia M.; Burnum-Johnson, Kristin E.; Orton, Daniel J.; Monroe, Matthew E.; Moore, Ronald J.; Smith, Richard D.; Baker, Erin M.

    2017-06-12

    Ion mobility spectrometry (IMS) is a widely used analytical technique for rapid molecular separations in the gas phase. IMS alone is useful, but its coupling with mass spectrometry (MS) and front-end separations has been extremely beneficial for increasing measurement sensitivity, peak capacity of complex mixtures, and the scope of molecular information in biological and environmental sample analyses. Multiple studies in disease screening and environmental evaluations have even shown these IMS-based multidimensional separations extract information not possible with each technique individually. This review highlights 3-dimensional separations using IMS-MS in conjunction with a range of front-end techniques, such as gas chromatography (GC), supercritical fluid chromatography (SFC), liquid chromatography (LC), solid phase extractions (SPE), capillary electrophoresis (CE), field asymmetric ion mobility spectrometry (FAIMS), and microfluidic devices. The origination, current state, various applications, and future capabilities for these multidimensional approaches are described to provide insight into the utility and potential of each technique.

  2. X-ray spectrometry

    Markowicz, A.A.; Van Grieken, R.E.

    1986-01-01

    In the period under review, i.e, through 1984 and 1985, some 600 articles on XRS (X-ray spectrometry) were published; most of these have been scanned and the most fundamental ones are discussed. All references will refer to English-language articles, unless states otherwise. Also general books have appeared on quantitative EPXMA (electron-probe X-ray microanalysis) and analytical electron microscopy (AEM) as well as an extensive review on the application of XRS to trace analysis of environmental samples. In the period under review no radically new developments have been seen in XRS. However, significant improvements have been made. Gain in intensities has been achieved by more efficient excitation, higher reflectivity of dispersing media, and better geometry. Better understanding of the physical process of photon- and electron-specimen interactions led to complex but more accurate equations for correction of various interelement effects. Extensive use of micro- and minicomputers now enables fully automatic operation, including qualitative analysis. However, sample preparation and presentation still put a limit to further progress. Although some authors find XRS in the phase of stabilization or even stagnation, further gradual developments are expected, particularly toward more dedicated equipment, advanced automation, and image analysis systems. Ways are outlined in which XRS has been improved in the 2 last years by excitation, detection, instrumental, methodological, and theoretical advances. 340 references

  3. Accelerator mass spectrometry.

    Hellborg, Ragnar; Skog, Göran

    2008-01-01

    In this overview the technique of accelerator mass spectrometry (AMS) and its use are described. AMS is a highly sensitive method of counting atoms. It is used to detect very low concentrations of natural isotopic abundances (typically in the range between 10(-12) and 10(-16)) of both radionuclides and stable nuclides. The main advantages of AMS compared to conventional radiometric methods are the use of smaller samples (mg and even sub-mg size) and shorter measuring times (less than 1 hr). The equipment used for AMS is almost exclusively based on the electrostatic tandem accelerator, although some of the newest systems are based on a slightly different principle. Dedicated accelerators as well as older "nuclear physics machines" can be found in the 80 or so AMS laboratories in existence today. The most widely used isotope studied with AMS is 14C. Besides radiocarbon dating this isotope is used in climate studies, biomedicine applications and many other fields. More than 100,000 14C samples are measured per year. Other isotopes studied include 10Be, 26Al, 36Cl, 41Ca, 59Ni, 129I, U, and Pu. Although these measurements are important, the number of samples of these other isotopes measured each year is estimated to be less than 10% of the number of 14C samples. Copyright 2008 Wiley Periodicals, Inc.

  4. Fast Multi-blind Modification Search through Tandem Mass Spectrometry*

    Na, Seungjin; Bandeira, Nuno; Paek, Eunok

    2012-01-01

    With great biological interest in post-translational modifications (PTMs), various approaches have been introduced to identify PTMs using MS/MS. Recent developments for PTM identification have focused on an unrestrictive approach that searches MS/MS spectra for all known and possibly even unknown types of PTMs at once. However, the resulting expanded search space requires much longer search time and also increases the number of false positives (incorrect identifications) and false negatives (missed true identifications), thus creating a bottleneck in high throughput analysis. Here we introduce MODa, a novel “multi-blind” spectral alignment algorithm that allows for fast unrestrictive PTM searches with no limitation on the number of modifications per peptide while featuring over an order of magnitude speedup in relation to existing approaches. We demonstrate the sensitivity of MODa on human shotgun proteomics data where it reveals multiple mutations, a wide range of modifications (including glycosylation), and evidence for several putative novel modifications. Based on the reported findings, we argue that the efficiency and sensitivity of MODa make it the first unrestrictive search tool with the potential to fully replace conventional restrictive identification of proteomics mass spectrometry data. PMID:22186716

  5. Fast neutron spectrometry and dosimetry

    Blaize, S.; Ailloud, J.; Mariani, J.; Millot, J.P.

    1958-01-01

    We have studied fast neutron spectrometry and dosimetry through the recoil protons they produce in hydrogenated samples. In spectrometric, we used nuclear emulsions, in dosimetric, we used polyethylene coated with zinc sulphide and placed before a photomultiplier. (author) [fr

  6. Mass Spectrometry of Halopyrazolium Salts

    Larsen, Elfinn; Egsgaard, Helge; Pande, U. C.

    1983-01-01

    Eleven halogen substituted 1-methyl-2-phenylpyrazolium bromides or chlorides were investigated by field desorption, field ionization, and electron impact mass spectrometry. Dealkylation was found to be the predominant thermal decomposition. An exchange between covalent and ionic halogen prior...

  7. Simulation of Two Dimensional Electrophoresis and Tandem Mass Spectrometry for Teaching Proteomics

    Fisher, Amanda; Sekera, Emily; Payne, Jill; Craig, Paul

    2012-01-01

    In proteomics, complex mixtures of proteins are separated (usually by chromatography or electrophoresis) and identified by mass spectrometry. We have created 2DE Tandem MS, a computer program designed for use in the biochemistry, proteomics, or bioinformatics classroom. It contains two simulations--2D electrophoresis and tandem mass spectrometry.…

  8. Interrogating the Venom of the Viperid Snake Sistrurus catenatus edwardsii by a Combined Approach of Electrospray and MALDI Mass Spectrometry.

    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.

  9. The Spatial Distribution of Alkaloids in Psychotria prunifolia (Kunth) Steyerm and Palicourea coriacea (Cham.) K. Schum Leaves Analysed by Desorption Electrospray Ionisation Mass Spectrometry Imaging

    Kato, Lucilia; Moraes, Aline Pereira; de Oliveira, Cecília Maria Alves

    2018-01-01

    INTRODUCTION: Species of the genera Psychotria and Palicourea are sources of indole alkaloids, however, the distribution of alkaloids within the plants is not known. Analysing the spatial distribution using desorption electrospray ionisation mass spectrometry imaging (DESI-MSI) has become...... analyses. METHODOLOGY: Based upon previous structure elucidation studies, four alkaloids targeted in this study were identified using high resolution mass spectrometry by direct infusion of plant extracts, and their distributions were imaged by DESI-MSI via tissue imprints on a porous Teflon surface....... Relative quantitation of the four alkaloids was obtained by HPLC-MS/MS analysis performed using multiple-reaction monitoring (MRM) mode on a triple quadrupole mass spectrometer. RESULTS: Alkaloids showed distinct distributions on the leaf surfaces. Prunifoleine was mainly present in the midrib, while 10...

  10. Multiple sclerosis

    Grunwald, I.Q.; Kuehn, A.L.; Backens, M.; Papanagiotou, P.; Shariat, K.; Kostopoulos, P.

    2008-01-01

    Multiple sclerosis is the most common chronic inflammatory disease of myelin with interspersed lesions in the white matter of the central nervous system. Magnetic resonance imaging (MRI) plays a key role in the diagnosis and monitoring of white matter diseases. This article focuses on key findings in multiple sclerosis as detected by MRI. (orig.) [de

  11. Flame emission, atomic absorption and fluorescence spectrometry

    Horlick, G.

    1980-01-01

    Six hundred and thirty references are cited in this review. The information in the review is divided into 12 major areas: books, reviews, and bibliographies; fundamental studies in flames; developments in instrumentation; measurement techniques and procedure; flame emission spectrometry; flame atomic absorption spectrometry; flame molecular absorption spectrometry; electrothermal atomization atomic absorption spectroscopy; hydride generation techniques; graphite furnace atomic emission spectrometry; atomic fluorescence spectrometry; and analytical comparisons

  12. Ultra-sensitive radionuclide spectrometry. Radiometrics and mass spectrometry synergy

    Povinec, P.P.

    2005-01-01

    Recent developments in radiometrics and mass spectrometry techniques for ultra-sensitive analysis of radionuclides in the marine environment are reviewed. In the radiometrics sector the dominant development has been the utilization of large HPGe detectors in underground laboratories with anti-cosmic or anti-Compton shielding for the analysis of short and medium-lived radionuclides in the environment. In the mass spectrometry sector, applications of inductively coupled plasma mass spectrometry (ICP-MS) and accelerator mass spectrometry (AMS) for the analysis of long-lived radionuclides in the environment are the most important recent achievements. The recent developments do not only considerably decrease the detection limits for several radionuclides (up to several orders of magnitude), but they also enable to decrease sample volumes so that sampling, e.g., of the water column can be much easier and more effective. A comparison of radiometrics and mass spectrometry results for the analysis of radionuclides in the marine environment shows a reasonable agreement - within quoted uncertainties, for wide range of activities and different sample matrices analyzed. (author)

  13. Cluster secondary ion mass spectrometry microscope mode mass spectrometry imaging.

    Kiss, András; Smith, Donald F; Jungmann, Julia H; Heeren, Ron M A

    2013-12-30

    Microscope mode imaging for secondary ion mass spectrometry is a technique with the promise of simultaneous high spatial resolution and high-speed imaging of biomolecules from complex surfaces. Technological developments such as new position-sensitive detectors, in combination with polyatomic primary ion sources, are required to exploit the full potential of microscope mode mass spectrometry imaging, i.e. to efficiently push the limits of ultra-high spatial resolution, sample throughput and sensitivity. In this work, a C60 primary source was combined with a commercial mass microscope for microscope mode secondary ion mass spectrometry imaging. The detector setup is a pixelated detector from the Medipix/Timepix family with high-voltage post-acceleration capabilities. The system's mass spectral and imaging performance is tested with various benchmark samples and thin tissue sections. The high secondary ion yield (with respect to 'traditional' monatomic primary ion sources) of the C60 primary ion source and the increased sensitivity of the high voltage detector setup improve microscope mode secondary ion mass spectrometry imaging. The analysis time and the signal-to-noise ratio are improved compared with other microscope mode imaging systems, all at high spatial resolution. We have demonstrated the unique capabilities of a C60 ion microscope with a Timepix detector for high spatial resolution microscope mode secondary ion mass spectrometry imaging. Copyright © 2013 John Wiley & Sons, Ltd.

  14. Whole exome sequencing identified 1 base pair novel deletion in BCL2-associated athanogene 3 (BAG3) gene associated with severe dilated cardiomyopathy (DCM) requiring heart transplant in multiple family members.

    Rafiq, Muhammad Arshad; Chaudhry, Ayeshah; Care, Melanie; Spears, Danna A; Morel, Chantal F; Hamilton, Robert M

    2017-03-01

    Dilated cardiomyopathy (DCM) is characterized by dilation and impaired contraction of the left ventricle or both ventricles. Among hereditary DCM, the genetic causes are heterogeneous, and include mutations encoding cytoskeletal, nucleoskeletal, mitochondrial, and calcium-handling proteins. We report three severely affected males, in a four-generation pedigree, with DCM phenotype who underwent cardiac transplant. Cardiomegaly with marked biventricular dilation and fibrosis were noticeable histopathological findings. The affected males had tested negative on a 46-gene pancardiomyopathy panel. Whole Exome Sequencing (WES) was performed to reveal mutation in the gene responsible in generation of DCM phenotypes. The 1-bp (Chr10:121435979delC; c.913delC) novel heterozygous deletion in exon 4 of BAG3, was identified in three affected males, resulted in frame-shift and a premature termination codon (p.Met306-Stop) producing a truncated BAG3 protein lacking functionally important PXXP and BAG domains. WES data were further utilized to map 10 SNP markers around the discovered mutation to generate shared disease haplotype in all affected individuals encompassing 11 Mb on 10q25.3-26.2 harboring BAG3. Finally genotypes were inferred for the unavailable/deceased individuals in the pedigrees. Here we propose that Chr10:121435979delC in BAG3 is a causal mutation in these subjects. Our and earlier studies indicate that BAG3 mutations are associated with DCM phenotypes. BAG3 should be added to cardiomyopathy gene panels for screening of DCM patients, and patients previously considered gene elusive should undergo sequencing of the BAG3 gene. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  15. Identification of Secreted Candida Proteins Using Mass Spectrometry

    Gómez-Molero, E.; Dekker, H.L.; de Boer, A.D.; de Groot, P.W.; Calderone, R.; Cihlar, R.

    2016-01-01

    Analysis of fungal secretomes using mass spectrometry is a useful technique in cell biology. Knowledge of the secretome of a human fungal pathogen may yield important information of host-pathogen interactions and may be useful for identifying vaccines candidates or diagnostic markers for antifungal

  16. Mass Spectrometry Imaging for the Classification of Tumor Tissue

    Mascini, N.E.

    2016-01-01

    Mass spectrometry imaging (MSI) can detect and identify many different molecules without the need for labeling. In addition, it can provide their spatial distributions as ‘molecular maps’. These features make MSI well suited for studying the molecular makeup of tumor tissue. Currently, there is an

  17. Applications of accelerator mass spectrometry: advances and innovation

    Fifield, L.K.

    2004-01-01

    Emerging trends in the applications of accelerator mass spectrometry (AMS) are identified and illustrated with specific examples. Areas of application covered include rapid landscape evolution, calibration of the radiocarbon time scale, compound-specific radiocarbon studies, tracing of nuclear discharges, and searches for extraterrestrial isotopes

  18. Dynamic Secondary Ion Mass Spectrometry | Materials Science | NREL

    Ion Mass Spectrometry (SIMS) uses a continuous, focused beam of primary ions to remove material from the surface of a sample by sputtering. The fraction of sputtered material that is ionized is extracted Identifies all elements or isotopes present in a material, from hydrogen to uranium. Different primary-ion

  19. Multiple homicides.

    Copeland, A R

    1989-09-01

    A study of multiple homicides or multiple deaths involving a solitary incident of violence by another individual was performed on the case files of the Office of the Medical Examiner of Metropolitan Dade County in Miami, Florida, during 1983-1987. A total of 107 multiple homicides were studied: 88 double, 17 triple, one quadruple, and one quintuple. The 236 victims were analyzed regarding age, race, sex, cause of death, toxicologic data, perpetrator, locale of the incident, and reason for the incident. This article compares this type of slaying with other types of homicide including those perpetrated by serial killers. Suggestions for future research in this field are offered.

  20. Imputation and subset-based association analysis across different cancer types identifies multiple independent risk loci in the TERT-CLPTM1L region on chromosome 5p15.33

    Wang, Zhaoming; Zhu, Bin; Zhang, Mingfeng; Parikh, Hemang; Jia, Jinping; Chung, Charles C.; Sampson, Joshua N.; Hoskins, Jason W.; Hutchinson, Amy; Burdette, Laurie; Ibrahim, Abdisamad; Hautman, Christopher; Raj, Preethi S.; Abnet, Christian C.; Adjei, Andrew A.; Ahlbom, Anders; Albanes, Demetrius; Allen, Naomi E.; Ambrosone, Christine B.; Aldrich, Melinda; Amiano, Pilar; Amos, Christopher; Andersson, Ulrika; Andriole, Gerald; Andrulis, Irene L.; Arici, Cecilia; Arslan, Alan A.; Austin, Melissa A.; Baris, Dalsu; Barkauskas, Donald A.; Bassig, Bryan A.; Beane Freeman, Laura E.; Berg, Christine D.; Berndt, Sonja I.; Bertazzi, Pier Alberto; Biritwum, Richard B.; Black, Amanda; Blot, William; Boeing, Heiner; Boffetta, Paolo; Bolton, Kelly; Boutron-Ruault, Marie-Christine; Bracci, Paige M.; Brennan, Paul; Brinton, Louise A.; Brotzman, Michelle; Bueno-de-Mesquita, H. Bas; Buring, Julie E.; Butler, Mary Ann; Cai, Qiuyin; Cancel-Tassin, Geraldine; Canzian, Federico; Cao, Guangwen; Caporaso, Neil E.; Carrato, Alfredo; Carreon, Tania; Carta, Angela; Chang, Gee-Chen; Chang, I-Shou; Chang-Claude, Jenny; Che, Xu; Chen, Chien-Jen; Chen, Chih-Yi; Chen, Chung-Hsing; Chen, Constance; Chen, Kuan-Yu; Chen, Yuh-Min; Chokkalingam, Anand P.; Chu, Lisa W.; Clavel-Chapelon, Francoise; Colditz, Graham A.; Colt, Joanne S.; Conti, David; Cook, Michael B.; Cortessis, Victoria K.; Crawford, E. David; Cussenot, Olivier; Davis, Faith G.; De Vivo, Immaculata; Deng, Xiang; Ding, Ti; Dinney, Colin P.; Di Stefano, Anna Luisa; Diver, W. Ryan; Duell, Eric J.; Elena, Joanne W.; Fan, Jin-Hu; Feigelson, Heather Spencer; Feychting, Maria; Figueroa, Jonine D.; Flanagan, Adrienne M.; Fraumeni, Joseph F.; Freedman, Neal D.; Fridley, Brooke L.; Fuchs, Charles S.; Gago-Dominguez, Manuela; Gallinger, Steven; Gao, Yu-Tang; Gapstur, Susan M.; Garcia-Closas, Montserrat; Garcia-Closas, Reina; Gastier-Foster, Julie M.; Gaziano, J. Michael; Gerhard, Daniela S.; Giffen, Carol A.; Giles, Graham G.; Gillanders, Elizabeth M.; Giovannucci, Edward L.; Goggins, Michael; Gokgoz, Nalan; Goldstein, Alisa M.; Gonzalez, Carlos; Gorlick, Richard; Greene, Mark H.; Gross, Myron; Grossman, H. Barton; Grubb, Robert; Gu, Jian; Guan, Peng; Haiman, Christopher A.; Hallmans, Goran; Hankinson, Susan E.; Harris, Curtis C.; Hartge, Patricia; Hattinger, Claudia; Hayes, Richard B.; He, Qincheng; Helman, Lee; Henderson, Brian E.; Henriksson, Roger; Hoffman-Bolton, Judith; Hohensee, Chancellor; Holly, Elizabeth A.; Hong, Yun-Chul; Hoover, Robert N.; Hosgood, H. Dean; Hsiao, Chin-Fu; Hsing, Ann W.; Hsiung, Chao Agnes; Hu, Nan; Hu, Wei; Hu, Zhibin; Huang, Ming-Shyan; Hunter, David J.; Inskip, Peter D.; Ito, Hidemi; Jacobs, Eric J.; Jacobs, Kevin B.; Jenab, Mazda; Ji, Bu-Tian; Johansen, Christoffer; Johansson, Mattias; Johnson, Alison; Kaaks, Rudolf; Kamat, Ashish M.; Kamineni, Aruna; Karagas, Margaret; Khanna, Chand; Khaw, Kay-Tee; Kim, Christopher; Kim, In-Sam; Kim, Jin Hee; Kim, Yeul Hong; Kim, Young-Chul; Kim, Young Tae; Kang, Chang Hyun; Jung, Yoo Jin; Kitahara, Cari M.; Klein, Alison P.; Klein, Robert; Kogevinas, Manolis; Koh, Woon-Puay; Kohno, Takashi; Kolonel, Laurence N.; Kooperberg, Charles; Kratz, Christian P.; Krogh, Vittorio; Kunitoh, Hideo; Kurtz, Robert C.; Kurucu, Nilgun; Lan, Qing; Lathrop, Mark; Lau, Ching C.; Lecanda, Fernando; Lee, Kyoung-Mu; Lee, Maxwell P.; Le Marchand, Loic; Lerner, Seth P.; Li, Donghui; Liao, Linda M.; Lim, Wei-Yen; Lin, Dongxin; Lin, Jie; Lindstrom, Sara; Linet, Martha S.; Lissowska, Jolanta; Liu, Jianjun; Ljungberg, Börje; Lloreta, Josep; Lu, Daru; Ma, Jing; Malats, Nuria; Mannisto, Satu; Marina, Neyssa; Mastrangelo, Giuseppe; Matsuo, Keitaro; McGlynn, Katherine A.; McKean-Cowdin, Roberta; McNeill, Lorna H.; McWilliams, Robert R.; Melin, Beatrice S.; Meltzer, Paul S.; Mensah, James E.; Miao, Xiaoping; Michaud, Dominique S.; Mondul, Alison M.; Moore, Lee E.; Muir, Kenneth; Niwa, Shelley; Olson, Sara H.; Orr, Nick; Panico, Salvatore; Park, Jae Yong; Patel, Alpa V.; Patino-Garcia, Ana; Pavanello, Sofia; Peeters, Petra H. M.; Peplonska, Beata; Peters, Ulrike; Petersen, Gloria M.; Picci, Piero; Pike, Malcolm C.; Porru, Stefano; Prescott, Jennifer; Pu, Xia; Purdue, Mark P.; Qiao, You-Lin; Rajaraman, Preetha; Riboli, Elio; Risch, Harvey A.; Rodabough, Rebecca J.; Rothman, Nathaniel; Ruder, Avima M.; Ryu, Jeong-Seon; Sanson, Marc; Schned, Alan; Schumacher, Fredrick R.; Schwartz, Ann G.; Schwartz, Kendra L.; Schwenn, Molly; Scotlandi, Katia; Seow, Adeline; Serra, Consol; Serra, Massimo; Sesso, Howard D.; Severi, Gianluca; Shen, Hongbing; Shen, Min; Shete, Sanjay; Shiraishi, Kouya; Shu, Xiao-Ou; Siddiq, Afshan; Sierrasesumaga, Luis; Sierri, Sabina; Loon Sihoe, Alan Dart; Silverman, Debra T.; Simon, Matthias; Southey, Melissa C.; Spector, Logan; Spitz, Margaret; Stampfer, Meir; Stattin, Par; Stern, Mariana C.; Stevens, Victoria L.; Stolzenberg-Solomon, Rachael Z.; Stram, Daniel O.; Strom, Sara S.; Su, Wu-Chou; Sund, Malin; Sung, Sook Whan; Swerdlow, Anthony; Tan, Wen; Tanaka, Hideo; Tang, Wei; Tang, Ze-Zhang; Tardon, Adonina; Tay, Evelyn; Taylor, Philip R.; Tettey, Yao; Thomas, David M.; Tirabosco, Roberto; Tjonneland, Anne; Tobias, Geoffrey S.; Toro, Jorge R.; Travis, Ruth C.; Trichopoulos, Dimitrios; Troisi, Rebecca; Truelove, Ann; Tsai, Ying-Huang; Tucker, Margaret A.; Tumino, Rosario; Van Den Berg, David; Van Den Eeden, Stephen K.; Vermeulen, Roel; Vineis, Paolo; Visvanathan, Kala; Vogel, Ulla; Wang, Chaoyu; Wang, Chengfeng; Wang, Junwen; Wang, Sophia S.; Weiderpass, Elisabete; Weinstein, Stephanie J.; Wentzensen, Nicolas; Wheeler, William; White, Emily; Wiencke, John K.; Wolk, Alicja; Wolpin, Brian M.; Wong, Maria Pik; Wrensch, Margaret; Wu, Chen; Wu, Tangchun; Wu, Xifeng; Wu, Yi-Long; Wunder, Jay S.; Xiang, Yong-Bing; Xu, Jun; Yang, Hannah P.; Yang, Pan-Chyr; Yatabe, Yasushi; Ye, Yuanqing; Yeboah, Edward D.; Yin, Zhihua; Ying, Chen; Yu, Chong-Jen; Yu, Kai; Yuan, Jian-Min; Zanetti, Krista A.; Zeleniuch-Jacquotte, Anne; Zheng, Wei; Zhou, Baosen; Mirabello, Lisa; Savage, Sharon A.; Kraft, Peter; Chanock, Stephen J.; Yeager, Meredith; Landi, Maria Terese; Shi, Jianxin; Chatterjee, Nilanjan; Amundadottir, Laufey T.

    2014-01-01

    Genome-wide association studies (GWAS) have mapped risk alleles for at least 10 distinct cancers to a small region of 63 000 bp on chromosome 5p15.33. This region harbors the TERT and CLPTM1L genes; the former encodes the catalytic subunit of telomerase reverse transcriptase and the latter may play a role in apoptosis. To investigate further the genetic architecture of common susceptibility alleles in this region, we conducted an agnostic subset-based meta-analysis (association analysis based on subsets) across six distinct cancers in 34 248 cases and 45 036 controls. Based on sequential conditional analysis, we identified as many as six independent risk loci marked by common single-nucleotide polymorphisms: five in the TERT gene (Region 1: rs7726159, P = 2.10 × 10−39; Region 3: rs2853677, P = 3.30 × 10−36 and PConditional = 2.36 × 10−8; Region 4: rs2736098, P = 3.87 × 10−12 and PConditional = 5.19 × 10−6, Region 5: rs13172201, P = 0.041 and PConditional = 2.04 × 10−6; and Region 6: rs10069690, P = 7.49 × 10−15 and PConditional = 5.35 × 10−7) and one in the neighboring CLPTM1L gene (Region 2: rs451360; P = 1.90 × 10−18 and PConditional = 7.06 × 10−16). Between three and five cancers mapped to each independent locus with both risk-enhancing and protective effects. Allele-specific effects on DNA methylation were seen for a subset of risk loci, indicating that methylation and subsequent effects on gene expression may contribute to the biology of risk variants on 5p15.33. Our results provide strong support for extensive pleiotropy across this region of 5p15.33, to an extent not previously observed in other cancer susceptibility loci. PMID:25027329

  1. Energy and depth resolution in elastic recoil coincidence spectrometry

    Szilagyi, E., E-mail: szilagyi@rmki.kfki.h [KFKI Research Institute for Particle and Nuclear Physics, P.O. Box 49, H-1525 Budapest (Hungary)

    2010-06-15

    Elastic recoil coincidence spectrometry was implemented into the analytical ion beam simulation program DEPTH. In the calculations, effective detector geometry and multiple scattering effects are considered. Mott's cross section for the identical, spin zero particles is included. Spectra based on the individual detector signal and summing the energy of the recoiled and scattered particles originating from the same scattering events can also be calculated. To calculate this latter case, the dependency of the energy spread contributions had to be reconsidered.

  2. Energy and depth resolution in elastic recoil coincidence spectrometry

    Szilagyi, E.

    2010-01-01

    Elastic recoil coincidence spectrometry was implemented into the analytical ion beam simulation program DEPTH. In the calculations, effective detector geometry and multiple scattering effects are considered. Mott's cross section for the identical, spin zero particles is included. Spectra based on the individual detector signal and summing the energy of the recoiled and scattered particles originating from the same scattering events can also be calculated. To calculate this latter case, the dependency of the energy spread contributions had to be reconsidered.

  3. Recent development in isotope ratio mass spectrometry

    Platzner, I.

    1992-01-01

    Within the limited of this review the following topics will be briefly discussed: a) Accuracy, precision, internal relative standard deviation (RISD) and external relative standard deviation (RESD) of isotope ratio measurements. With advanced instrumentation and use of standard reference materials, high accuracy and RESD = 0.002% (or better) may be achieved; b) The advantages of modern automatic isotope ratio mass spectrometer are briefly described. Computer controlled operation and data acquisition, and multiple ion collection are the recent important improvement; c) The isotopic fractionation during the course of isotope ratio measurement is considered as a major source of errors in thermal ionization of metallic elements. The phenomenon in strontium, neodymium, uranium, lead and calcium and methods to correct the measured data are discussed; d) Applications of isotope ratio mass spectrometry in atomic weight determinations, the isotope dilution technique, isotope geology, and isotope effects in biological systems are described together with specific applications in various research and technology area. (author)

  4. Mass Spectrometry Identification of N-Chlorinated Dipeptides in Drinking Water.

    Huang, Guang; Jiang, Ping; Li, Xing-Fang

    2017-04-04

    We report the identification of N-chlorinated dipeptides as chlorination products in drinking water using complementary high-resolution quadrupole time-of-flight (QTOF) and quadrupole ion-trap mass spectrometry techniques. First, three model dipeptides, tyrosylglycine (Tyr-Gly), tyrosylalanine (Tyr-Ala), and phenylalanylglycine (Phe-Gly), reacted with sodium hypochlorite, and these reaction solutions were analyzed by QTOF. N-Cl-Tyr-Gly, N,N-di-Cl-Tyr-Gly, N-Cl-Phe-Gly, N,N-di-Cl-Phe-Gly, N-Cl-Tyr-Ala, and N,N-di-Cl-Tyr-Ala were identified as the major products based on accurate masses, 35 Cl/ 37 Cl isotopic patterns, and MS/MS spectra. These identified N-chlorinated dipeptides were synthesized and found to be stable in water over 10 days except N,N-di-Cl-Phe-Gly. To enable sensitive detection of N-chlorinated dipeptides in authentic water, we developed a high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method with multiple reaction monitoring (MRM) mode. N-Cl-Tyr-Gly, N,N-di-Cl-Tyr-Gly, N-Cl-Phe-Gly, N-Cl-Tyr-Ala, and N,N-di-Cl-Tyr-Ala along with their corresponding dipeptides were detected in authentic tap water samples. The dipeptides were clearly detected in the raw water, but the N-chlorinated dipeptides were at background levels. These results suggest that the N-chlorinated dipeptides are produced by chlorination. This study has identified N-chlorinated dipeptides as new disinfection byproducts in drinking water. The strategy developed in this study can be used to identify chlorination products of other peptides in drinking water.

  5. Multiple Sclerosis

    Multiple sclerosis (MS) is a nervous system disease that affects your brain and spinal cord. It damages the myelin sheath, the material that surrounds and protects your nerve cells. This damage slows down ...

  6. Multiple myeloma.

    Collins, Conor D

    2012-02-01

    Advances in the imaging and treatment of multiple myeloma have occurred over the past decade. This article summarises the current status and highlights how an understanding of both is necessary for optimum management.

  7. Multiple mononeuropathy

    ... with multiple mononeuropathy are prone to new nerve injuries at pressure points such as the knees and elbows. They should avoid putting pressure on these areas, for example, by not leaning on the elbows, crossing the knees, ...

  8. Critical Evaluation of Native Electrospray Ionization Mass Spectrometry for Fragment-Based Screening.

    Göth, Melanie; Badock, Volker; Weiske, Jörg; Pagel, Kevin; Kuropka, Benno

    2017-08-08

    Fragment-based screening presents a promising alternative to high-throughput screening and has gained great attention in recent years. So far, only a few studies have discussed mass spectrometry as a screening technology for fragments. Herein, we report the application of native electrospray ionization mass spectrometry (MS) for screening defined sets of fragments against four different target proteins. Fragments were selected from a primary screening conducted with a thermal shift assay (TSA) and represented different binding categories. Our data indicated that, beside specific complex formation, many fragments show extensive multiple binding and also charge-state shifts. Both of these factors complicate automated data analysis and decrease the attractiveness of native MS as a primary screening tool for fragments. A comparison of the hits identified by native MS and TSA showed good agreement for two of the proteins. Furthermore, we discuss general challenges, including the determination of an optimal fragment concentration and the question of how to rank fragment hits according to their affinity. In conclusion, we consider native MS to be a highly valuable tool for the validation and deeper investigation of promising fragment hits rather than a method for primary screening. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  9. Recent advancements and future trends in environmental analysis: Sample preparation, liquid chromatography and mass spectrometry.

    Pérez-Fernández, Virginia; Mainero Rocca, Lucia; Tomai, Pierpaolo; Fanali, Salvatore; Gentili, Alessandra

    2017-08-29

    Among the thousands of chemicals having potential to enter the environment, the NORMAN network has identified at least 700 substances categorized into 20 classes in the European surface waters. Pesticides, pharmaceuticals, disinfection by-products, wood preservation and industrial chemicals are the prominent classes. Since the impact of these substances on aquatic life and human health might be dramatic, action is urgently required at multiple levels; one of them is just related to the development of more and more sensible and selective analytical methods. This review highlights the latest advancements and trends in liquid chromatography-mass spectrometry based environmental analysis. Specific sections are dedicated to novelties in sample preparation, chromatographic separation and mass spectrometry detection of emerging pollutants. The review also offers insights on last generation chromatographic and extraction materials, technological progresses and innovative methodological approaches for target and non-target analysis. As numerous papers have been published in this field, this overview covers the most representative and original works published in the 2011-2016 period. Copyright © 2017 Elsevier B.V. All rights reserved.

  10. Beyond the ridge pattern: multi-informative analysis of latent fingermarks by MALDI mass spectrometry.

    Francese, S; Bradshaw, R; Ferguson, L S; Wolstenholme, R; Clench, M R; Bleay, S

    2013-08-07

    After over a century, fingerprints are still one of the most powerful means of biometric identification. The conventional forensic workflow for suspect identification consists of (i) recovering latent marks from crime scenes using the appropriate enhancement technique and (ii) obtaining an image of the mark to compare either against known suspect prints and/or to search in a Fingerprint Database. The suspect is identified through matching the ridge pattern and local characteristics of the ridge pattern (minutiae). However successful, there are a number of scenarios in which this process may fail; they include the recovery of partial, distorted or smudged marks, poor quality of the image resulting from inadequacy of the enhancement technique applied, extensive scarring/abrasion of the fingertips or absence of suspect's fingerprint records in the database. In all of these instances it would be very desirable to have a technology able to provide additional information from a fingermark exploiting its endogenous and exogenous chemical content. This opportunity could potentially provide new investigative leads, especially when the fingermark comparison and match process fails. We have demonstrated that Matrix Assisted Laser Desorption Ionisation Mass Spectrometry and Mass Spectrometry Imaging (MALDI MSI) can provide multiple images of the same fingermark in one analysis simultaneous with additional intelligence. Here, a review on the pioneering use and development of MALDI MSI for the analysis of latent fingermarks is presented along with the latest achievements on the forensic intelligence retrievable.

  11. Multiple Intelligences and quotient spaces

    Malatesta, Mike; Quintana, Yamilet

    2006-01-01

    The Multiple Intelligence Theory (MI) is one of the models that study and describe the cognitive abilities of an individual. In [7] is presented a referential system which allows to identify the Multiple Intelligences of the students of a course and to classify the level of development of such Intelligences. Following this tendency, the purpose of this paper is to describe the model of Multiple Intelligences as a quotient space, and also to study the Multiple Intelligences of an individual in...

  12. Large-scale analysis of peptide sequence variants: the case for high-field asymmetric waveform ion mobility spectrometry.

    Creese, Andrew J; Smart, Jade; Cooper, Helen J

    2013-05-21

    Large scale analysis of proteins by mass spectrometry is becoming increasingly routine; however, the presence of peptide isomers remains a significant challenge for both identification and quantitation in proteomics. Classes of isomers include sequence inversions, structural isomers, and localization variants. In many cases, liquid chromatography is inadequate for separation of peptide isomers. The resulting tandem mass spectra are composite, containing fragments from multiple precursor ions. The benefits of high-field asymmetric waveform ion mobility spectrometry (FAIMS) for proteomics have been demonstrated by a number of groups, but previously work has focused on extending proteome coverage generally. Here, we present a systematic study of the benefits of FAIMS for a key challenge in proteomics, that of peptide isomers. We have applied FAIMS to the analysis of a phosphopeptide library comprising the sequences GPSGXVpSXAQLX(K/R) and SXPFKXpSPLXFG(K/R), where X = ADEFGLSTVY. The library has defined limits enabling us to make valid conclusions regarding FAIMS performance. The library contains numerous sequence inversions and structural isomers. In addition, there are large numbers of theoretical localization variants, allowing false localization rates to be determined. The FAIMS approach is compared with reversed-phase liquid chromatography and strong cation exchange chromatography. The FAIMS approach identified 35% of the peptide library, whereas LC-MS/MS alone identified 8% and LC-MS/MS with strong cation exchange chromatography prefractionation identified 17.3% of the library.

  13. Identifying and annotating human bifunctional RNAs reveals their versatile functions.

    Chen, Geng; Yang, Juan; Chen, Jiwei; Song, Yunjie; Cao, Ruifang; Shi, Tieliu; Shi, Leming

    2016-10-01

    Bifunctional RNAs that possess both protein-coding and noncoding functional properties were less explored and poorly understood. Here we systematically explored the characteristics and functions of such human bifunctional RNAs by integrating tandem mass spectrometry and RNA-seq data. We first constructed a pipeline to identify and annotate bifunctional RNAs, leading to the characterization of 132 high-confidence bifunctional RNAs. Our analyses indicate that bifunctional RNAs may be involved in human embryonic development and can be functional in diverse tissues. Moreover, bifunctional RNAs could interact with multiple miRNAs and RNA-binding proteins to exert their corresponding roles. Bifunctional RNAs may also function as competing endogenous RNAs to regulate the expression of many genes by competing for common targeting miRNAs. Finally, somatic mutations of diverse carcinomas may generate harmful effect on corresponding bifunctional RNAs. Collectively, our study not only provides the pipeline for identifying and annotating bifunctional RNAs but also reveals their important gene-regulatory functions.

  14. MetaboSearch: tool for mass-based metabolite identification using multiple databases.

    Bin Zhou

    Full Text Available Searching metabolites against databases according to their masses is often the first step in metabolite identification for a mass spectrometry-based untargeted metabolomics study. Major metabolite databases include Human Metabolome DataBase (HMDB, Madison Metabolomics Consortium Database (MMCD, Metlin, and LIPID MAPS. Since each one of these databases covers only a fraction of the metabolome, integration of the search results from these databases is expected to yield a more comprehensive coverage. However, the manual combination of multiple search results is generally difficult when identification of hundreds of metabolites is desired. We have implemented a web-based software tool that enables simultaneous mass-based search against the four major databases, and the integration of the results. In addition, more complete chemical identifier information for the metabolites is retrieved by cross-referencing multiple databases. The search results are merged based on IUPAC International Chemical Identifier (InChI keys. Besides a simple list of m/z values, the software can accept the ion annotation information as input for enhanced metabolite identification. The performance of the software is demonstrated on mass spectrometry data acquired in both positive and negative ionization modes. Compared with search results from individual databases, MetaboSearch provides better coverage of the metabolome and more complete chemical identifier information.The software tool is available at http://omics.georgetown.edu/MetaboSearch.html.

  15. Development of stereotactic mass spectrometry for brain tumor surgery.

    Agar, Nathalie Y R; Golby, Alexandra J; Ligon, Keith L; Norton, Isaiah; Mohan, Vandana; Wiseman, Justin M; Tannenbaum, Allen; Jolesz, Ferenc A

    2011-02-01

    Surgery remains the first and most important treatment modality for the majority of solid tumors. Across a range of brain tumor types and grades, postoperative residual tumor has a great impact on prognosis. The principal challenge and objective of neurosurgical intervention is therefore to maximize tumor resection while minimizing the potential for neurological deficit by preserving critical tissue. To introduce the integration of desorption electrospray ionization mass spectrometry into surgery for in vivo molecular tissue characterization and intraoperative definition of tumor boundaries without systemic injection of contrast agents. Using a frameless stereotactic sampling approach and by integrating a 3-dimensional navigation system with an ultrasonic surgical probe, we obtained image-registered surgical specimens. The samples were analyzed with ambient desorption/ionization mass spectrometry and validated against standard histopathology. This new approach will enable neurosurgeons to detect tumor infiltration of the normal brain intraoperatively with mass spectrometry and to obtain spatially resolved molecular tissue characterization without any exogenous agent and with high sensitivity and specificity. Proof of concept is presented in using mass spectrometry intraoperatively for real-time measurement of molecular structure and using that tissue characterization method to detect tumor boundaries. Multiple sampling sites within the tumor mass were defined for a patient with a recurrent left frontal oligodendroglioma, World Health Organization grade II with chromosome 1p/19q codeletion, and mass spectrometry data indicated a correlation between lipid constitution and tumor cell prevalence. The mass spectrometry measurements reflect a complex molecular structure and are integrated with frameless stereotaxy and imaging, providing 3-dimensional molecular imaging without systemic injection of any agents, which can be implemented for surgical margins delineation of

  16. Symposium on accelerator mass spectrometry

    1981-01-01

    The area of accelerator mass spectrometry has expanded considerably over the past few years and established itself as an independent and interdisciplinary research field. Three years have passed since the first meeting was held at Rochester. A Symposium on Accelerator Mass Spectrometry was held at Argonne on May 11-13, 1981. In attendance were 96 scientists of whom 26 were from outside the United States. The present proceedings document the program and excitement of the field. Papers are arranged according to the original program. A few papers not presented at the meeting have been added to complete the information on the status of accelerator mass spectrometry. Individual papers were prepared separately for the data base

  17. Symposium on accelerator mass spectrometry

    None

    1981-01-01

    The area of accelerator mass spectrometry has expanded considerably over the past few years and established itself as an independent and interdisciplinary research field. Three years have passed since the first meeting was held at Rochester. A Symposium on Accelerator Mass Spectrometry was held at Argonne on May 11-13, 1981. In attendance were 96 scientists of whom 26 were from outside the United States. The present proceedings document the program and excitement of the field. Papers are arranged according to the original program. A few papers not presented at the meeting have been added to complete the information on the status of accelerator mass spectrometry. Individual papers were prepared separately for the data base.

  18. Mass spectrometry. [in organic chemistry

    Burlingame, A. L.; Shackleton, C. H. L.; Howe, I.; Chizhov, O. S.

    1978-01-01

    A review of mass spectrometry in organic chemistry is given, dealing with advances in instrumentation and computer techniques, selected topics in gas-phase ion chemistry, and applications in such fields as biomedicine, natural-product studies, and environmental pollution analysis. Innovative techniques and instrumentation are discussed, along with chromatographic-mass spectrometric on-line computer techniques, mass spectral interpretation and management techniques, and such topics in gas-phase ion chemistry as electron-impact ionization and decomposition, photoionization, field ionization and desorption, high-pressure mass spectrometry, ion cyclotron resonance, and isomerization reactions of organic ions. Applications of mass spectrometry are examined with respect to bio-oligomers and their constituents, biomedically important substances, microbiology, environmental organic analysis, and organic geochemistry.

  19. Plant trait detection with multi-scale spectrometry

    Gamon, J. A.; Wang, R.

    2017-12-01

    Proximal and remote sensing using imaging spectrometry offers new opportunities for detecting plant traits, with benefits for phenotyping, productivity estimation, stress detection, and biodiversity studies. Using proximal and airborne spectrometry, we evaluated variation in plant optical properties at various spatial and spectral scales with the goal of identifying optimal scales for distinguishing plant traits related to photosynthetic function. Using directed approaches based on physiological vegetation indices, and statistical approaches based on spectral information content, we explored alternate ways of distinguishing plant traits with imaging spectrometry. With both leaf traits and canopy structure contributing to the signals, results exhibit a strong scale dependence. Our results demonstrate the benefits of multi-scale experimental approaches within a clear conceptual framework when applying remote sensing methods to plant trait detection for phenotyping, productivity, and biodiversity studies.

  20. Screening and identification of steroidal saponins from Anemarrhena asphodeloides employing UPLC tandem triple quadrupole linear ion trap mass spectrometry.

    Xia, Yong-Gang; Guo, Xin-Dong; Liang, Jun; Yang, Bing-You; Kuang, Hai-Xue

    2017-09-01

    This study presents a practical and valid strategy for the screening and structural characterization of Anemarrhena asphodeloides Bge steroidal saponins (SSs) using ultra-high performance liquid chromatography coupled with triple quadrupole linear ion trap mass spectrometry. The whole analytical protocols integrate four-step procedures in the positive mode: (1) rational deduction of mass fragmentation pathways of A. asphodeloides SSs; (2) untargeted screening of potential A. asphodeloides SSs by multiple-ion monitoring-information-dependent-acquiring-enhanced product ion (MIM-IDA-EPI) scan through reverse phase liquid chromatography; (3) comprehensive construction of an ammoniated precursor ion database by combining untargeted MIM-IDA-EPI scans and data literature; and (4) structural interpretation of targeted A. asphodeloides SSs using MIM-IDA-EPI and multiple reaction monitoring (MRM)-IDA-EPI with an energy-resolved technique. The protocols were used to analyze SSs in A. asphodeloides; of the 87 detected SSs that were unambiguously characterized or tentatively identified, 19 compounds were the first to be reported from A. asphodeloides and 13 ones were characterized as potential new compounds. Accuracy of the analytical procedure was demonstrated by structural identification of three SSs by NMR spectroscopy. The proposed schemes hold an excellent promise in the structural prediction and interpretation of complex SSs from plant medicines by mass spectrometry. Copyright © 2017 Elsevier Inc. All rights reserved.

  1. Mass spectrometry for biomarker development

    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.

  2. [Multiple meningiomas].

    Terrier, L-M; François, P

    2016-06-01

    Multiple meningiomas (MMs) or meningiomatosis are defined by the presence of at least 2 lesions that appear simultaneously or not, at different intracranial locations, without the association of neurofibromatosis. They present 1-9 % of meningiomas with a female predominance. The occurrence of multiple meningiomas is not clear. There are 2 main hypotheses for their development, one that supports the independent evolution of these tumors and the other, completely opposite, that suggests the propagation of tumor cells of a unique clone transformation, through cerebrospinal fluid. NF2 gene mutation is an important intrinsic risk factor in the etiology of multiple meningiomas and some exogenous risk factors have been suspected but only ionizing radiation exposure has been proven. These tumors can grow anywhere in the skull but they are more frequently observed in supratentorial locations. Their histologic types are similar to unique meningiomas of psammomatous, fibroblastic, meningothelial or transitional type and in most cases are benign tumors. The prognosis of these tumors is eventually good and does not differ from the unique tumors except for the cases of radiation-induced multiple meningiomas, in the context of NF2 or when diagnosed in children where the outcome is less favorable. Each meningioma lesion should be dealt with individually and their multiple character should not justify their resection at all costs. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  3. Gray Matter Is Targeted in First-Attack Multiple Sclerosis

    Schutzer, Steven E.; Angel, Thomas E.; Liu, Tao; Schepmoes, Athena A.; Xie, Fang; Bergquist, Jonas P.; Vecsei, Lazlo' ; Zadori, Denes; Camp, David G.; Holland, Bart K.; Smith, Richard D.; Coyle, Patricia K.

    2013-09-10

    The cause of multiple sclerosis (MS), its driving pathogenesis at the earliest stages, and what factors allow the first clinical attack to manifest remain unknown. Some imaging studies suggest gray rather than white matter may be involved early, and some postulate this may be predictive of developing MS. Other imaging studies are in conflict. To determine if there was objective molecular evidence of gray matter involvement in early MS we used high-resolution mass spectrometry to identify proteins in the cerebrospinal fluid (CSF) of first-attack MS patients (two independent groups) compared to established relapsing remitting (RR) MS and controls. We found that the CSF proteins in first-attack patients were differentially enriched for gray matter components (axon, neuron, synapse). Myelin components did not distinguish these groups. The results support that gray matter dysfunction is involved early in MS, and also may be integral for the initial clinical presentation.

  4. Quantification of Fatty Acid Oxidation Products Using On-line High Performance Liquid Chromatography Tandem Mass Spectrometry

    Levison, Bruce S.; Zhang, Renliang; Wang, Zeneng; Fu, Xiaoming; DiDonato, Joseph A.; Hazen, Stanley L.

    2013-01-01

    Oxidized fatty acids formed via lipid peroxidation are implicated in pathological processes such as inflammation and atherosclerosis. A number of methods may be used to detect specific oxidized fatty acids containing a single or multiple combinations of epoxide, hydroxyl, ketone and hydroperoxide moieties on varying carbon chain lengths from C8 up to C30. Some of these methods are nonspecific and their use in biological systems is fraught with difficulty. Measures of specific-oxidized fatty acid derivatives help in identifying oxidation pathways in pathological processes. We used liquid chromatography coupled with electrospray ionization tandem mass spectrometry (LC-MS/MS) as efficient, selective and sensitive methods for identifying and analyzing multiple specific fatty acid peroxidation products in human plasma and other biological matrices. We then distilled the essential components of a number of these analyses to provide an efficient protocol by which fatty acid oxidation products and their parent compounds can be determined. In this protocol, addition of synthetic internal standard to the sample, followed by base hydrolysis at elevated temperature, and liquid-liquid phase sample extraction with lighter than water solvents facilitates isolation of the oxidized fatty acid species. These species can be identified and accurately quantified using stable isotope dilution and multiple reaction monitoring. Use of a coupled multiplexed gradient HPLC system on the front end enables high-throughput chromatography and more efficient use of mass spectrometer time. PMID:23499838

  5. Target and identify: triazene linker helps identify azidation sites of labelled proteins via click and cleave strategy.

    Lohse, Jonas; Schindl, Alexandra; Danda, Natasha; Williams, Chris P; Kramer, Karl; Kuster, Bernhard; Witte, Martin D; Médard, Guillaume

    2017-10-31

    A method for identifying probe modification of proteins via tandem mass spectrometry was developed. Azide bearing molecules are immobilized on functionalised sepharose beads via copper catalysed Huisgen-type click chemistry and selectively released under acidic conditions by chemical cleavage of the triazene linkage. We applied this method to identify the modification site of targeted-diazotransfer on BirA.

  6. On the analysis of glycomics mass spectrometry data via the regularized area under the ROC curve

    Lebrilla Carlito B

    2007-12-01

    Full Text Available Abstract Background Novel molecular and statistical methods are in rising demand for disease diagnosis and prognosis with the help of recent advanced biotechnology. High-resolution mass spectrometry (MS is one of those biotechnologies that are highly promising to improve health outcome. Previous literatures have identified some proteomics biomarkers that can distinguish healthy patients from cancer patients using MS data. In this paper, an MS study is demonstrated which uses glycomics to identify ovarian cancer. Glycomics is the study of glycans and glycoproteins. The glycans on the proteins may deviate between a cancer cell and a normal cell and may be visible in the blood. High-resolution MS has been applied to measure relative abundances of potential glycan biomarkers in human serum. Multiple potential glycan biomarkers are measured in MS spectra. With the objection of maximizing the empirical area under the ROC curve (AUC, an analysis method was considered which combines potential glycan biomarkers for the diagnosis of cancer. Results Maximizing the empirical AUC of glycomics MS data is a large-dimensional optimization problem. The technical difficulty is that the empirical AUC function is not continuous. Instead, it is in fact an empirical 0–1 loss function with a large number of linear predictors. An approach was investigated that regularizes the area under the ROC curve while replacing the 0–1 loss function with a smooth surrogate function. The constrained threshold gradient descent regularization algorithm was applied, where the regularization parameters were chosen by the cross-validation method, and the confidence intervals of the regression parameters were estimated by the bootstrap method. The method is called TGDR-AUC algorithm. The properties of the approach were studied through a numerical simulation study, which incorporates the positive values of mass spectrometry data with the correlations between measurements within person

  7. Multiple sclerosis

    Stenager, Egon; Stenager, E N; Knudsen, Lone

    1994-01-01

    In a cross-sectional study of 117 randomly selected patients (52 men, 65 women) with definite multiple sclerosis, it was found that 76 percent were married or cohabitant, 8 percent divorced. Social contacts remained unchanged for 70 percent, but outgoing social contacts were reduced for 45 percent......, need for structural changes in home and need for pension became greater with increasing physical handicap. No significant differences between gender were found. It is concluded that patients and relatives are under increased social strain, when multiple sclerosis progresses to a moderate handicap...

  8. Immunochip Analysis Identifies Multiple Susceptibility Loci for Systemic Sclerosis

    Mayes, Maureen D.; Bossini-Castillo, Lara; Gorlova, Olga; Martin, Jose Ezequiel; Zhou, Xiaodong; Chen, Wei V.; Assassi, Shervin; Ying, Jun; Tan, Filemon K.; Arnett, Frank C.; Reveille, John D.; Guerra, Sandra; Terue, Maria; Carmona, Francisco David; Gregersen, Peter K.; Lee, Annette T.; Lopez-Isac, Elena; Ochoa, Eguzkine; Carreira, Patricia; Simeon, Carmen Pilar; Castellvi, Ivan; Angel Gonzalez-Gay, Miguel; Zhernakova, Alexandra; Padyukov, Leonid; Aarcon-Riquelme, Marta; Wijmenga, Cisca; Beretta, Lorenzo; Riemekasten, Gabriela; Witte, Torsten; Hunzelmann, Nicolas; Kreuter, Alexander; Distler, Jorg H. W.; Voskuy, Alexandre E.; Schuerwegh, Annemie J.; Hesselstrand, Roger; Nordin, Annika; Airo, Paolo; Lunardi, Claudio; Shiels, Paul; van Laar, Jacob M.; Herrick, Ariane; Worthington, Jane; Denton, Christopher; Wigley, Fredrick M.; Hummers, Laura K.; Varga, John; Hinchcliff, Monique E.; Baron, Murray; Hudson, Marie; Pope, Janet E.

    2014-01-01

    In this study, 1,833 systemic sclerosis (SSc) cases and 3,466 controls were genotyped with the Immunochip array. Classical alleles, amino acid residues, and SNPs across the human leukocyte antigen (HLA) region were imputed and tested. These analyses resulted in a model composed of six polymorphic

  9. Some analytical aspects of the Moessbauer spectrometry

    Meisel, W.

    1975-01-01

    Analytical applications of Moessbauer spectrometry are reviewed. Various methods of analysis (qualitative, semiquantitative and quantitative) using the Moessbauer effect are dealt with. Sensitivity and accuracy of Moessbauer spectrometry in analytical applications are discussed. (Z.S.)

  10. Multiple Primary Cancer Monograph

    To identify groups of cancer survivors that are at increased risk for multiple primary cancers, investigators led an effort to provide the first comprehensive population-based analysis of the risk of subsequent cancer in the U.S., resulting in a monograph.

  11. A Review of the Emerging Field of Underwater Mass Spectrometry

    Emily Chua

    2016-11-01

    Full Text Available Mass spectrometers are versatile sensor systems, owing to their high sensitivity and ability to simultaneously measure multiple chemical species. Over the last two decades, traditional laboratory-based membrane inlet mass spectrometers have been adapted for underwater use. Underwater mass spectrometry has drastically improved our capability to monitor a broad suite of gaseous compounds (e.g., dissolved atmospheric gases, light hydrocarbons, and volatile organic compounds in the aquatic environment. Here we provide an overview of the progress made in the field of underwater mass spectrometry since its inception in the 1990s to the present. In particular, we discuss the approaches undertaken by various research groups in developing in situ mass spectrometers. We also provide examples to illustrate how underwater mass spectrometers have been used in the field. Finally, we present future trends in the field of in situ mass spectrometry. Most of these efforts are aimed at improving the quality and spatial and temporal scales of chemical measurements in the ocean. By providing up-to-date information on underwater mass spectrometry, this review offers guidance for researchers interested in adapting this technology as well as goals for future progress in the field.

  12. X-ray fluorescence spectrometry

    Vries, J.L. de.

    1976-01-01

    The seventh edition of Philips' Review of Literature on x-ray fluorescence spectrometry starts with a list of conference proceedings on the subject, organised by the Philips organisation at regular intervals in various European countries. It is followed by a list of bulletins. The bibliography is subdivided according to spectra, equipment, applications and absorption analysis

  13. Mass spectrometry in epigenetic research

    Beck, Hans Christian

    2010-01-01

    cancers has gained tremendous interest in recent years, and many of these inhibitors are currently undergoing clinical trials. Despite intense research, however, the exact molecular mechanisms of action of these molecules remain, to a wide extent, unclear. The recent application of mass spectrometry...

  14. X-ray fluorescence spectrometry

    Ray, N.B.

    1977-01-01

    The principle, instrument and procedure of X-ray fluorescence spectrometry are described. It is a rapid, simple and sensitive method for the trace analysis of elements from sodium to uranium in powder, liquid or metal samples. (M.G.B.)

  15. Mass spectrometry of large molecules

    Facchetti, S.

    1985-01-01

    The lectures in this volume were given at a course on mass spectrometry of large molecules, organized within the framework of the Training and Education programme of the Joint Research Centre of the European Communities. Although first presented in 1983, most of the lectures have since been updated by their authors. (orig.)

  16. Gamma and X 93 spectrometry

    1994-05-01

    The Meetings of Gamma and X 93 Spectrometry were held on 12-14 October 1993. The symposium was organized into six sessions: Instrumentation development, Nuclear matter measurement, Method and calibration, Medical applications, Environment survey (radioactive traces measurement), other applications (spent fuels analysis, various techniques). Separate abstracts were prepared for all the papers in this volume. (TEC)

  17. Mass spectrometry with particle accelerator

    Anon.

    1983-01-01

    The heavy ion accelerator use is renewing the ultrasensitive mass spectrometry in extending the detection limits. These new devices allow the measurement of rare isotope ratio, as 10 Be, 14 C, 26 Al, 36 Cl or 41 Ca, from the earth natural reservoirs [fr

  18. Eleventh ISMAS workshop on mass spectrometry

    Aggarwal, S.K.; Jaison, P.G.

    2004-10-01

    This volume deals with the latest developments in this field, exposing the innumerable applications of mass spectrometry. The topics covered include basic fundamentals of mass spectrometry, qualitative and quantitative aspects and data interpretation, maintenance of mass spectrometers, selection of a mass spectrometer, its applications in various branches of science as well as recent advances in mass spectrometry. Emphasis is also laid on the practical aspects of mass spectrometry. Papers relevant to INIS are indexed separately

  19. Urban gamma spectrometry. Report 1

    Aage, H.K.; Kuukankorpi, S.; Moring, M.; Smolander, P.; Toivonen, H.

    2009-06-01

    This report contains the present status and results for the NKS UGS-project per 1 June 2006 for NKS partners DTU, Denmark, and STUK, Finland. The Danish and Finnish CGS (Carborne Gamma Spectrometry) systems are not of similar types. The Danish CGS system(s) only make use of one NaI(Tl) detector whereas the Finnish CGS system consists of several detectors, NaI(Tl) and HPGe both and as an additional feature the Finnish detectors have position dependent different fields of view. Furthermore, the Finnish system is equipped with an air sampling system. In terms of operation, the Danish detector is located on the rooftop where as the Finnish detectors are located inside the vehicle. The Finnish and the Danish team use different methods for data processing. STUK uses a hypothesis test method to get robust real time alarms (within 10 seconds) when significant peaks from a previously defined set of nuclides are detected. An alarm for a significantly elevated total pulse rate is sent if none of the predefined nuclides is identified. All data are stored to the LINSSI database, which facilitates easy data retrieval for post processing. DEMA/DTU bases their calculations on full spectrum fitting using NASVD and the Danish software NucSpec. Source signals are found from spectrum fitting residuals or from stripping of energy windows - either by the standard 4-windows method or by a measurement based method where stripping factors for any window of interest can be derived from the measurements themselves. A thorough description of the two systems and data processing methods (including mathematics) are described in this report. For the Danish methods of data processing some comparisons have been made, but no final conclusion has been reached yet. Raw urban data has been investigated along with urban data sets to which source signals have been added and searched for. For the Finnish method calibration plots of the minimum detection limits for two different detector types have been

  20. Urban gamma spectrometry. Report 1

    Aage, H K [Technical Univ. of Denmark, Kgs. Lyngby (Denmark); Kuukankorpi, S; Moring, M; Smolander, P; Toivonen, H [Radiation and Nuclear Safety Authority, Helsinki (Finland)

    2009-06-15

    This report contains the present status and results for the NKS UGS-project per 1 June 2006 for NKS partners DTU, Denmark, and STUK, Finland. The Danish and Finnish CGS (Carborne Gamma Spectrometry) systems are not of similar types. The Danish CGS system(s) only make use of one NaI(Tl) detector whereas the Finnish CGS system consists of several detectors, NaI(Tl) and HPGe both and as an additional feature the Finnish detectors have position dependent different fields of view. Furthermore, the Finnish system is equipped with an air sampling system. In terms of operation, the Danish detector is located on the rooftop where as the Finnish detectors are located inside the vehicle. The Finnish and the Danish team use different methods for data processing. STUK uses a hypothesis test method to get robust real time alarms (within 10 seconds) when significant peaks from a previously defined set of nuclides are detected. An alarm for a significantly elevated total pulse rate is sent if none of the predefined nuclides is identified. All data are stored to the LINSSI database, which facilitates easy data retrieval for post processing. DEMA/DTU bases their calculations on full spectrum fitting using NASVD and the Danish software NucSpec. Source signals are found from spectrum fitting residuals or from stripping of energy windows - either by the standard 4-windows method or by a measurement based method where stripping factors for any window of interest can be derived from the measurements themselves. A thorough description of the two systems and data processing methods (including mathematics) are described in this report. For the Danish methods of data processing some comparisons have been made, but no final conclusion has been reached yet. Raw urban data has been investigated along with urban data sets to which source signals have been added and searched for. For the Finnish method calibration plots of the minimum detection limits for two different detector types have been

  1. Multiple myeloma

    Sohn, Jeong Ick; Ha, Choon Ho; Choi, Karp Shik

    1994-01-01

    Multiple myeloma is a malignant plasma cell tumor that is thought to originate proliferation of a single clone of abnormal plasma cell resulting production of a whole monoclonal paraprotein. The authors experienced a case of multiple myeloma with severe mandibular osteolytic lesions in 46-year-old female. As a result of careful analysis of clinical, radiological, histopathological features, and laboratory findings, we diagnosed it as multiple myeloma, and the following results were obtained. 1. Main clinical symptoms were intermittent dull pain on the mandibular body area, abnormal sensation of lip and pain due to the fracture on the right clavicle. 2. Laboratory findings revealed M-spike, reversed serum albumin-globulin ratio, markedly elevated ESR and hypercalcemia. 3. Radiographically, multiple osteolytic punched-out radiolucencies were evident on the skull, zygoma, jaw bones, ribs, clavicle and upper extremities. Enlarged liver and increased uptakes on the lesional sites in RN scan were also observed. 4. Histopathologically, markedly hypercellular marrow with sheets of plasmoblasts and megakaryocytes were also observed.

  2. Multiple sclerosis

    Stenager, E; Jensen, K

    1988-01-01

    Forty-two (12%) of a total of 366 patients with multiple sclerosis (MS) had psychiatric admissions. Of these, 34 (81%) had their first psychiatric admission in conjunction with or after the onset of MS. Classification by psychiatric diagnosis showed that there was a significant positive correlation...

  3. Multiple sclerosis

    Stenager, E; Knudsen, L; Jensen, K

    1991-01-01

    In a cross-sectional investigation of 116 patients with multiple sclerosis, the social and sparetime activities of the patient were assessed by both patient and his/her family. The assessments were correlated to physical disability which showed that particularly those who were moderately disabled...

  4. Multiple sclerosis

    Stenager, E; Jensen, K

    1990-01-01

    An investigation on the correlation between ability to read TV subtitles and the duration of visual evoked potential (VEP) latency in 14 patients with definite multiple sclerosis (MS), indicated that VEP latency in patients unable to read the TV subtitles was significantly delayed in comparison...

  5. Multiple sclerosis

    Stenager, E; Knudsen, L; Jensen, K

    1994-01-01

    In a cross-sectional study of 94 patients (42 males, 52 females) with definite multiple sclerosis (MS) in the age range 25-55 years, the correlation of neuropsychological tests with the ability to read TV-subtitles and with the use of sedatives is examined. A logistic regression analysis reveals...

  6. Multiple Sclerosis.

    Plummer, Nancy; Michael, Nancy, Ed.

    This module on multiple sclerosis is intended for use in inservice or continuing education programs for persons who administer medications in long-term care facilities. Instructor information, including teaching suggestions, and a listing of recommended audiovisual materials and their sources appear first. The module goal and objectives are then…

  7. Parenting Multiples

    ... when your babies do. Though it can be hard to let go of the thousand other things you need to do, remember that your well-being is key to your ability to take care of your babies. What Problems Can Happen? It may be hard to tell multiple babies apart when they first ...

  8. Lipid imaging by mass spectrometry - a review.

    Gode, David; Volmer, Dietrich A

    2013-03-07

    Mass spectrometry imaging (MSI) has proven to be extremely useful for applications such as the spatial analysis of peptides and proteins in biological tissue, the performance assessment of drugs in vivo or the measurement of protein or metabolite expression as tissue classifiers or biomarkers from disease versus control tissue comparisons. The most popular MSI technique is MALDI mass spectrometry. First invented by Richard Caprioli in the mid-1990s, it is the highest performing MSI technique in terms of spatial resolution, sensitivity for intact biomolecules and application range today. The unique ability to identify and spatially resolve numerous compounds simultaneously, based on m/z values has inter alia been applied to untargeted and targeted chemical mapping of biological compartments, revealing changes of physiological states, disease pathologies and metabolic faith and distribution of xenobiotics. Many MSI applications focus on lipid species because of the lipids' diverse roles as structural components of cell membranes, their function in the surfactant cycle, and their involvement as second messengers in signalling cascades of tissues and cells. This article gives a comprehensive overview of lipid imaging techniques and applications using established MALDI and SIMS methods but also other promising MSI techniques such as DESI.

  9. [Mass spectrometry in the clinical microbiology laboratory].

    Jordana-Lluch, Elena; Martró Català, Elisa; Ausina Ruiz, Vicente

    2012-12-01

    Infectious diseases are still a cause of high mortality and morbidity rates. Current microbiological diagnostic methods are based on culture and phenotypic identification of isolated microorganisms, which can be obtained in about 24-48 h. Given that the microbiological identification is of major importance for patient management, new diagnostic methods are needed in order to detect and identify microorganisms in a timely and accurate manner. Over the last few years, several molecular techniques based on the amplification of microbial nucleic acids have been developed with the aim of reducing the time needed for the identification of the microorganisms involved in different infectious processes. On the other hand, mass spectrometry has emerged as a rapid and consistent alternative to conventional methods for microorganism identification. This review describes the most widely used mass spectrometry technologies -matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) and electrospray ionization time-of-flight (ESI-TOF)-, both for protein and nucleic acid analysis, as well as the commercial platforms available. Related publications of most interest in clinical microbiology are also reviewed. Copyright © 2011 Elsevier España, S.L. All rights reserved.

  10. Multiple sclerosis

    Sadashima, Hiromichi; Kusaka, Hirofumi; Imai, Terukuni; Takahashi, Ryosuke; Matsumoto, Sadayuki; Yamamoto, Toru; Yamasaki, Masahiro; Maya, Kiyomi

    1986-01-01

    Eleven patients with a definite diagnosis of multiple sclerosis were examined in terms of correlations between the clinical features and the results of cranial computed tomography (CT), and magnetic resonance imaging (MRI). Results: In 5 of the 11 patients, both CT and MRI demonstrated lesions consistent with a finding of multiple sclerosis. In 3 patients, only MRI demonstrated lesions. In the remaining 3 patients, neither CT nor MRI revealed any lesion in the brain. All 5 patients who showed abnormal findings on both CT and MRI had clinical signs either of cerebral or brainstem - cerebellar lesions. On the other hand, two of the 3 patients with normal CT and MRI findings had optic-nerve and spinal-cord signs. Therefore, our results suggested relatively good correlations between the clinical features, CT, and MRI. MRI revealed cerebral lesions in two of the four patients with clinical signs of only optic-nerve and spinal-cord lesions. MRI demonstrated sclerotic lesions in 3 of the 6 patients whose plaques were not detected by CT. In conclusion, MRI proved to be more helpful in the demonstration of lesions attributable to chronic multiple sclerosis. (author)

  11. Ninth ISMAS workshop on mass spectrometry

    Aggarwal, S.K.

    2000-12-01

    Mass spectrometry has wide-ranging applications in such diverse areas as nuclear industry, agriculture, drugs, environment, petroleum and lentils. There is an urgent need to absorb and assimilate state-of-the-art technological developments in the field. Emerging trends in atomic mass spectrometry, advances in organic mass spectrometry, qualitative and quantitative analyses by mass spectrometry and mass spectrometry in oceanography are some of the areas that need to be expeditiously examined and are covered in this volume. Papers relevant to INIS are indexed separately

  12. Computational mass spectrometry for small molecules

    2013-01-01

    The identification of small molecules from mass spectrometry (MS) data remains a major challenge in the interpretation of MS data. This review covers the computational aspects of identifying small molecules, from the identification of a compound searching a reference spectral library, to the structural elucidation of unknowns. In detail, we describe the basic principles and pitfalls of searching mass spectral reference libraries. Determining the molecular formula of the compound can serve as a basis for subsequent structural elucidation; consequently, we cover different methods for molecular formula identification, focussing on isotope pattern analysis. We then discuss automated methods to deal with mass spectra of compounds that are not present in spectral libraries, and provide an insight into de novo analysis of fragmentation spectra using fragmentation trees. In addition, this review shortly covers the reconstruction of metabolic networks using MS data. Finally, we list available software for different steps of the analysis pipeline. PMID:23453222

  13. Cloud-based solution to identify statistically significant MS peaks differentiating sample categories.

    Ji, Jun; Ling, Jeffrey; Jiang, Helen; Wen, Qiaojun; Whitin, John C; Tian, Lu; Cohen, Harvey J; Ling, Xuefeng B

    2013-03-23

    Mass spectrometry (MS) has evolved to become the primary high throughput tool for proteomics based biomarker discovery. Until now, multiple challenges in protein MS data analysis remain: large-scale and complex data set management; MS peak identification, indexing; and high dimensional peak differential analysis with the concurrent statistical tests based false discovery rate (FDR). "Turnkey" solutions are needed for biomarker investigations to rapidly process MS data sets to identify statistically significant peaks for subsequent validation. Here we present an efficient and effective solution, which provides experimental biologists easy access to "cloud" computing capabilities to analyze MS data. The web portal can be accessed at http://transmed.stanford.edu/ssa/. Presented web application supplies large scale MS data online uploading and analysis with a simple user interface. This bioinformatic tool will facilitate the discovery of the potential protein biomarkers using MS.

  14. Statistical methods for quantitative mass spectrometry proteomic experiments with labeling

    Oberg Ann L

    2012-11-01

    Full Text Available Abstract Mass Spectrometry utilizing labeling allows multiple specimens to be subjected to mass spectrometry simultaneously. As a result, between-experiment variability is reduced. Here we describe use of fundamental concepts of statistical experimental design in the labeling framework in order to minimize variability and avoid biases. We demonstrate how to export data in the format that is most efficient for statistical analysis. We demonstrate how to assess the need for normalization, perform normalization, and check whether it worked. We describe how to build a model explaining the observed values and test for differential protein abundance along with descriptive statistics and measures of reliability of the findings. Concepts are illustrated through the use of three case studies utilizing the iTRAQ 4-plex labeling protocol.

  15. Statistical methods for quantitative mass spectrometry proteomic experiments with labeling.

    Oberg, Ann L; Mahoney, Douglas W

    2012-01-01

    Mass Spectrometry utilizing labeling allows multiple specimens to be subjected to mass spectrometry simultaneously. As a result, between-experiment variability is reduced. Here we describe use of fundamental concepts of statistical experimental design in the labeling framework in order to minimize variability and avoid biases. We demonstrate how to export data in the format that is most efficient for statistical analysis. We demonstrate how to assess the need for normalization, perform normalization, and check whether it worked. We describe how to build a model explaining the observed values and test for differential protein abundance along with descriptive statistics and measures of reliability of the findings. Concepts are illustrated through the use of three case studies utilizing the iTRAQ 4-plex labeling protocol.

  16. Membrane introduction proton-transfer-reaction mass spectrometry

    Alexander, M.; Boscaini, E.; Maerk, T.; Lindinger, W.

    2002-01-01

    Proton-transfer-reaction mass spectrometry (PTR-MS) is a rapidly expanding field with multiple applications in ion physics, atmospheric chemistry, food chemistry, volatile organic compounds monitoring and biology. Initial studies that combine PTR-MS and membrane introduction mass spectrometry (MIMS) were researched and outlined. First using PTR-MS, certain fundamental physical properties of a poly-dimethylsiloxane (PDMS) membrane including solubilities and diffusion coefficients were measured. Second, it was shown how the chemical selectivity of the (PDMS) can be used to extend the capabilities of the PTR-MS instrument by eliminating certain isobaric interferences and excluding water from volatile organic compounds (VOCs). Experiments with mixtures of several VOCs (toluene, benzene, acetone, propanal, methanol) are presented. (nevyjel)

  17. Imaging Mass Spectrometry in Neuroscience

    2013-01-01

    Imaging mass spectrometry is an emerging technique of great potential for investigating the chemical architecture in biological matrices. Although the potential for studying neurobiological systems is evident, the relevance of the technique for application in neuroscience is still in its infancy. In the present Review, a principal overview of the different approaches, including matrix assisted laser desorption ionization and secondary ion mass spectrometry, is provided with particular focus on their strengths and limitations for studying different neurochemical species in situ and in vitro. The potential of the various approaches is discussed based on both fundamental and biomedical neuroscience research. This Review aims to serve as a general guide to familiarize the neuroscience community and other biomedical researchers with the technique, highlighting its great potential and suitability for comprehensive and specific chemical imaging. PMID:23530951

  18. Automatic gamma spectrometry analytical apparatus

    Lamargot, J.-P.; Wanin, Maurice.

    1980-01-01

    This invention falls within the area of quantitative or semi-quantitative analysis by gamma spectrometry and particularly refers to a device for bringing the samples into the counting position. The purpose of this invention is precisely to provide an automatic apparatus specifically adapted to the analysis of hard gamma radiations. To this effect, the invention relates to a gamma spectrometry analytical device comprising a lead containment, a detector of which the sensitive part is located inside the containment and additionally comprising a transfer system for bringing the analyzed samples in succession to a counting position inside the containment above the detector. A feed compartment enables the samples to be brought in turn one by one on to the transfer system through a duct connecting the compartment to the transfer system. Sequential systems for the coordinated forward feed of the samples in the compartment and the transfer system complete this device [fr

  19. Mass Spectrometry Instrumentation in Proteomics

    Sprenger, Richard Remko; Roepstorff, Peter

    2012-01-01

    Mass spectrometry has evolved into a crucial technology for the field of proteomics, enabling the comprehensive study of proteins in biological systems. Innovative developments have yielded flexible and versatile mass spectrometric tools, including quadrupole time-of-flight, linear ion trap......, Orbitrap and ion mobility instruments. Together they offer various and complementary capabilities in terms of ionization, sensitivity, speed, resolution, mass accuracy, dynamic range and methods of fragmentation. Mass spectrometers can acquire qualitative and quantitative information on a large scale...

  20. Mass Spectrometry Applications for Toxicology

    Mbughuni, Michael M.; Jannetto, Paul J.; Langman, Loralie J.

    2016-01-01

    Toxicology is a multidisciplinary study of poisons, aimed to correlate the quantitative and qualitative relationships between poisons and their physiological and behavioural effects in living systems. Other key aspects of toxicology focus on elucidation of the mechanisms of action of poisons and development of remedies and treatment plans for associated toxic effects. In these endeavours, Mass spectrometry (MS) has become a powerful analytical technique with a wide range of application used i...

  1. The history of radiation spectrometry

    Mori, Kunishiro

    2007-01-01

    Recently combination of charge sensitive amplifier, pulse shape amplifier and multi-channel PHA (MCA) is regarded as standard configuration of radiation spectrometry. PHA history shows various kinds of MCA devices before we have obtained original digital ADC technology based MCA in 1960s. Those MCAs include interesting ones such as photographic type, which still keep fresh ideas even today. Room temperature preamplifiers are classified to low, medium range, and large capacitance (over 10000pF) detectors keeping ultra low noise. (author)

  2. Instrumentation for mass spectrometry: 1997

    McLuckey, S.A.

    1997-08-01

    All mass spectrometry experiments involve the manipulation of material, an interface with the mass spectrometer, ionization, ion manipulation/analysis, detection and data collection/reduction. Each of these elements involve instrumentation. The wide range of species now amenable to mass spectrometry and the diverse areas of physical science in which it plays a role have led to a seemingly unlimited array of instrumental combinations. However, only a limited number of mass analyzers, and their combinations, dominate. The dominant analyzers include time-of-flight, Fourier transform ion cyclotron resonance, the Paul trap, the mass filter, and the sector mass spectrometer. Why there are so few (or so many, depending upon one`s point of view) can be understood upon consideration of a set of mass analyzer figures of merit. These include mass resolution, mass accuracy, mass range, dynamic range, abundance sensitivity, precision, efficiency, speed, MS{sup n} capability, compatibility with the ionizer, cost, and size. The most appropriate form of mass spectrometry is determined by the priorities of the particular measurement placed on the various mass analyzer characteristics and the relative strengths of the analyzers in meeting the requirements. Each of the analyzer types has a unique set of figures of merit that makes it optimally suited for particular applications. This paper discusses these figures of merit, provides data illustrating recent developments for each analyzer type, and gives the figures of merit of each type of analyzer as they stand in 1997. 101 refs., 24 figs.

  3. Characterization of a Distributed Plasma Ionization Source (DPIS) for Ion Mobility Spectrometry and Mass Spectrometry

    Waltman, Melanie J.; Dwivedi, Prabha; Hill, Herbert; Blanchard, William C.; Ewing, Robert G.

    2008-01-01

    A recently developed atmospheric pressure ionization source, a distributed plasma ionization source (DPIS), was characterized and compared to commonly used atmospheric pressure ionization sources with both mass spectrometry and ion mobility spectrometry. The source consisted of two electrodes of different sizes separated by a thin dielectric. Application of a high RF voltage across the electrodes generated plasma in air yielding both positive and negative ions depending on the polarity of the applied potential. These reactant ions subsequently ionized the analyte vapors. The reactant ions generated were similar to those created in a conventional point-to-plane corona discharge ion source. The positive reactant ions generated by the source were mass identified as being solvated protons of general formula (H2O)nH+ with (H2O)2H+ as the most abundant reactant ion. The negative reactant ions produced were mass identified primarily as CO3-, NO3-, NO2-, O3- and O2- of various relative intensities. The predominant ion and relative ion ratios varied depending upon source construction and supporting gas flow rates. A few compounds including drugs, explosives and environmental pollutants were selected to evaluate the new ionization source. The source was operated continuously for several months and although deterioration was observed visually, the source continued to produce ions at a rate similar that of the initial conditions. The results indicated that the DPIS may have a longer operating life than a conventional corona discharge.

  4. Atmospheric pressure photo ionization hydrogen/deuterium exchange mass spectrometry--a method to differentiate isomers by mass spectrometry.

    Ahmed, Arif; Kim, Sunghwan

    2013-12-01

    In this report, a method for in-source hydrogen/deuterium (H/D) exchange at atmospheric pressure is reported. The method was named atmospheric pressure photo ionization hydrogen/deuterium exchange mass spectrometry (APPI HDX MS). H/D exchange was performed by mixing samples dissolved in toluene with CH3OD solvent and analyzing the mixture using atmospheric pressure photo ionization mass spectrometry (APPI-MS). The APPI HDX spectra obtained with contact times between the analyte solution and methanol-OD (CH3OD) of atmospheric pressure. H/D exchange can be performed in any laboratory with a mass spectrometer and a commercial APPI source. Using this method, multiple H/D exchanges of aromatic hydrogen and/or H/D exchange of active hydrogen were observed. These results demonstrated that H/D exchange can be used to distinguish between isomers containing primary, secondary, and tertiary amines, as well as pyridine and pyrrole functional groups.

  5. On the Reproducibility of Label-Free Quantitative Cross-Linking/Mass Spectrometry

    Müller, Fränze; Fischer, Lutz; Chen, Zhuo Angel; Auchynnikava, Tania; Rappsilber, Juri

    2018-02-01

    Quantitative cross-linking/mass spectrometry (QCLMS) is an emerging approach to study conformational changes of proteins and multi-subunit complexes. Distinguishing protein conformations requires reproducibly identifying and quantifying cross-linked peptides. Here we analyzed the variation between multiple cross-linking reactions using bis[sulfosuccinimidyl] suberate (BS3)-cross-linked human serum albumin (HSA) and evaluated how reproducible cross-linked peptides can be identified and quantified by LC-MS analysis. To make QCLMS accessible to a broader research community, we developed a workflow that integrates the established software tools MaxQuant for spectra preprocessing, Xi for cross-linked peptide identification, and finally Skyline for quantification (MS1 filtering). Out of the 221 unique residue pairs identified in our sample, 124 were subsequently quantified across 10 analyses with coefficient of variation (CV) values of 14% (injection replica) and 32% (reaction replica). Thus our results demonstrate that the reproducibility of QCLMS is in line with the reproducibility of general quantitative proteomics and we establish a robust workflow for MS1-based quantitation of cross-linked peptides.

  6. Protein Alterations in Infiltrating Ductal Carcinomas of the Breast as Detected by Nonequilibrium pH Gradient Electrophoresis and Mass Spectrometry

    Maria Kabbage

    2008-01-01

    Full Text Available Improvement of breast-cancer detection through the identification of potential cancer biomarkers is considered as a promising strategy for effective assessment of the disease. The current study has used nonequilibrium pH gradient electrophoresis with subsequent analysis by mass spectrometry to identify protein alterations in invasive ductal carcinomas of the breast from Tunisian women. We have identified multiple protein alterations in tumor tissues that were picked, processed, and unambiguously assigned identities by matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF. The proteins identified span a wide range of functions and are believed to have potential clinical applications as cancer biomarkers. They include glycolytic enzymes, molecular chaperones, cytoskeletal-related proteins, antioxydant enzymes, and immunologic related proteins. Among these proteins, enolase 1, phosphoglycerate kinase 1, deoxyhemoglobin, Mn-superoxyde dismutase, α-B-crystallin, HSP27, Raf kinase inhibitor protein, heterogeneous nuclear ribonucleoprotein A2/B1, cofilin 1, and peptidylprolyl isomerase A were overexpressed in tumors compared with normal tissues. In contrast, the IGHG1 protein, the complement C3 component C3c, which are two newly identified protein markers, were downregulated in IDCA tissues.

  7. Hadron multiplicities at COMPASS

    Du Fresne von Hohenesche, Nicolas [Institut fuer Kernphysik, Universitaet Mainz, Johann-Joachim-Becher-Weg 45, 55128 Mainz (Germany); Collaboration: COMPASS Collaboration

    2014-07-01

    Quark fragmentation functions (FF) D{sub q}{sup h}(z,Q{sup 2}) describe final-state hadronization of quarks q into hadrons h. The FFs can be extracted from hadron multiplicities produced in semi-inclusive deep inelastic scattering. The COMPASS collaboration has recently measured charged hadron multiplicities for identified pions and kaons using a 160 GeV/c muon beam impinging on an iso-scalar target. The data cover a large kinematical range and provide an important input for global QCD analyses of world data at NLO, aiming at the determination of FFs in particular in the strange quark sector. The newest results from COMPASS on pion and kaon multiplicities will be presented.

  8. Multiple inflation

    Murphy, P.J.

    1987-01-01

    The Theory of Inflation, namely, that at some point the entropy content of the universe was greatly increased, has much promise. It may solve the puzzles of homogeneity and the creation of structure. However, no particle physics model has yet been found that can successfully drive inflation. The difficulty in satisfying the constraint that the isotropy of the microwave background places on the effective potential of prospective models is immense. In this work we have codified the requirements of such models in a most general form. We have carefully calculated the amounts of inflation the various problems of the Standard Model need for their solution. We have derived a completely model independent upper bond on the inflationary Hubble parameter. We have developed a general notation with which to probe the possibilities of Multiple Inflation. We have shown that only in very unlikely circumstances will any evidence of an earlier inflation, survive the de Sitter period of its successor. In particular, it is demonstrated that it is most unlikely that two bouts of inflation will yield high amplitudes of density perturbations on small scales and low amplitudes on large. We conclude that, while multiple inflation will be of great theoretical interest, it is unlikely to have any observational impact

  9. Urban gamma spectrometry. Report 2

    Aage, H.K. (Technical Univ. of Denmark, Kgs. Lyngby (Denmark)); Kuukankorpi, S.; Moring, M.; Smolander, P.; Toivonen, H. (Radiation and Nuclear Safety Authority, Helsinki (Finland))

    2009-06-15

    Urban gamma spectrometry has been given only minor attention with the focus being on rural gamma spectrometry. However, in recent years the Nordic emergency management authorities have turned focus towards border control and lost or stolen sources. Gamma spectra measured in urban areas are characterized by a wide variety of spectrum shapes and very fast changes in environmental background. In 2004 a Danish CGS (Carborne Gamma Spectrometry) survey took place in Copenhagen. It was found that gamma spectrometry in urban areas is far more complicated to interpret than had previously been thought and a new method 'Fitting with Spectral Components', FSC, based on NASVD, was tested with some success. In Finland, a database 'LINSSI' has been developed for spectral data management. In CGS search mode a 'peak hypothesis test' is applied to the measured spectra. This system was tested during the Helsinki 2005 Athletics World Championship and it provides fast and reliable automated alarms for intermediate and high level signals. In Sweden mobile detector systems are used for border controls and problems are encountered when making measurement in harbour, container areas. The methods for handling data and for interpretation of urban gamma spectrometry measurements were compared and tested on the same data sets from Copenhagen and Helsinki. Software tools were developed for converting data between the Finnish LINSSI database and the binary file formats used in Denmark and Sweden. The Processing methods used at DTU and STUK have different goals. The ASSS and FSC methods are designed to optimize the overall detection capability of the system, while sacrificing speed, usability and to a certain level robustness. These methods cannot always be used for real time analysis. The Peak Significance method is designed to give robust alarms in real time, while sacrificing some of the detection capability. Thus these methods are not interchangeable, but rather

  10. Urban gamma spectrometry. Report 2

    Aage, H.K.; Kuukankorpi, S.; Moring, M.; Smolander, P.; Toivonen, H.

    2009-06-01

    Urban gamma spectrometry has been given only minor attention with the focus being on rural gamma spectrometry. However, in recent years the Nordic emergency management authorities have turned focus towards border control and lost or stolen sources. Gamma spectra measured in urban areas are characterized by a wide variety of spectrum shapes and very fast changes in environmental background. In 2004 a Danish CGS (Carborne Gamma Spectrometry) survey took place in Copenhagen. It was found that gamma spectrometry in urban areas is far more complicated to interpret than had previously been thought and a new method 'Fitting with Spectral Components', FSC, based on NASVD, was tested with some success. In Finland, a database 'LINSSI' has been developed for spectral data management. In CGS search mode a 'peak hypothesis test' is applied to the measured spectra. This system was tested during the Helsinki 2005 Athletics World Championship and it provides fast and reliable automated alarms for intermediate and high level signals. In Sweden mobile detector systems are used for border controls and problems are encountered when making measurement in harbour, container areas. The methods for handling data and for interpretation of urban gamma spectrometry measurements were compared and tested on the same data sets from Copenhagen and Helsinki. Software tools were developed for converting data between the Finnish LINSSI database and the binary file formats used in Denmark and Sweden. The Processing methods used at DTU and STUK have different goals. The ASSS and FSC methods are designed to optimize the overall detection capability of the system, while sacrificing speed, usability and to a certain level robustness. These methods cannot always be used for real time analysis. The Peak Significance method is designed to give robust alarms in real time, while sacrificing some of the detection capability. Thus these methods are not interchangeable, but rather complementary. An ideal system

  11. Identification of keratinocyte specific markers using phage display and mass spectrometry

    Jensen, K.B.; Jensen, O.N.; Ravn, P.

    2003-01-01

    and mass spectrometry that allows identification of cell type-specific protein markers. The most important features of the method are (i) reduction of experimental noise originating from background binding of phage particles and (ii) isolation of affinity binders after a single round of selection, which...... antigens were subsequently identified by mass spectrometry as laminin-5, plectin, and fibronectin. The combination of phage display technology with mass spectrometry methods for protein identification is a general and promising approach for proteomic analysis of cell surface complexity....

  12. spatially identifying vulnerable areas

    The model structure is aimed at understanding the critical vulnerable factors that ... This paper incorporates multiple criteria and rank risk factors. ..... In terms of quantifying vulnerable areas within the country, the analysis is done based on 9 ...

  13. Affinity purification mass spectrometry analysis of PD-1 uncovers SAP as a new checkpoint inhibitor.

    Peled, Michael; Tocheva, Anna S; Sandigursky, Sabina; Nayak, Shruti; Philips, Elliot A; Nichols, Kim E; Strazza, Marianne; Azoulay-Alfaguter, Inbar; Askenazi, Manor; Neel, Benjamin G; Pelzek, Adam J; Ueberheide, Beatrix; Mor, Adam

    2018-01-16

    Programmed cell death-1 (PD-1) is an essential inhibitory receptor in T cells. Antibodies targeting PD-1 elicit durable clinical responses in patients with multiple tumor indications. Nevertheless, a significant proportion of patients do not respond to anti-PD-1 treatment, and a better understanding of the signaling pathways downstream of PD-1 could provide biomarkers for those whose tumors respond and new therapeutic approaches for those whose tumors do not. We used affinity purification mass spectrometry to uncover multiple proteins associated with PD-1. Among these proteins, signaling lymphocytic activation molecule-associated protein (SAP) was functionally and mechanistically analyzed for its contribution to PD-1 inhibitory responses. Silencing of SAP augmented and overexpression blocked PD-1 function. T cells from patients with X-linked lymphoproliferative disease (XLP), who lack functional SAP, were hyperresponsive to PD-1 signaling, confirming its inhibitory role downstream of PD-1. Strikingly, signaling downstream of PD-1 in purified T cell subsets did not correlate with PD-1 surface expression but was inversely correlated with intracellular SAP levels. Mechanistically, SAP opposed PD-1 function by acting as a molecular shield of key tyrosine residues that are targets for the tyrosine phosphatase SHP2, which mediates PD-1 inhibitory properties. Our results identify SAP as an inhibitor of PD-1 function and SHP2 as a potential therapeutic target in patients with XLP.

  14. High Resolution Mass Spectrometry of Polyfluorinated Polyether-Based Formulation

    Dimzon, Ian Ken; Trier, Xenia; Frömel, Tobias

    2016-01-01

    High resolution mass spectrometry (HRMS) was successfully applied to elucidate the structure of a polyfluorinated polyether (PFPE)-based formulation. The mass spectrum generated from direct injection into the MS was examined by identifying the different repeating units manually and with the aid o......-fluorinated polymers. The information from MS is essential in studying the physico-chemical properties of PFPEs and can help in assessing the risks they pose to the environment and to human health. Graphical Abstract ᅟ....

  15. Structure of [M + H − H2O]+ from Protonated Tetraglycine Revealed by Tandem Mass Spectrometry and IRMPD Spectroscopy

    Bythell, B. J.; Dain, Ryan P.; Curtice, Stephanie S.; Oomens, Jos; Steill, Jeffrey D.; Groenewold, Gary S.; la Paizs, Bé; van Stipdonk, M. J.

    2010-01-01

    Multiple-stage tandem mass spectrometry and collision-induced dissociation were used to investigate loss of H2O or CH3OH from protonated versions of GGGX (where X = G, A, and V), GGGGG, and the methyl esters of these peptides. In addition, wavelength-selective infrared multiple photon dissociation

  16. Mapping posttranscriptional modifications in 5S ribosomal RNA by MALDI mass spectrometry.

    Kirpekar, F; Douthwaite, S; Roepstorff, P

    2000-01-01

    We present a method to screen RNA for posttranscriptional modifications based on Matrix Assisted Laser Desorption/Ionization mass spectrometry (MALDI-MS). After the RNA is digested to completion with a nucleotide-specific RNase, the fragments are analyzed by mass spectrometry. A comparison of the observed mass data with the data predicted from the gene sequence identifies fragments harboring modified nucleotides. Fragments larger than dinucleotides were valuable for the identification of post...

  17. Vascular comorbidities in multiple sclerosis

    Thormann, Anja; Magyari, Melinda; Koch-Henriksen, Nils

    2016-01-01

    To investigate the occurrence of vascular comorbidities before and after the clinical onset of multiple sclerosis. In this combined case-control and cohort study, all Danish born citizens with onset of multiple sclerosis 1980-2005 were identified from the Danish Multiple Sclerosis Registry...... and randomly matched with controls regarding year of birth, gender, and municipality on January 1st in the year of multiple sclerosis (MS) onset (index date). Individual-level information on comorbidities was obtained from several independent nationwide registries and linked to the study population by unique...

  18. Identifying known unknowns using the US EPA's CompTox Chemistry Dashboard

    Chemical features observed using high-resolution mass spectrometry can be tentatively identified using online chemical reference databases by searching molecular formulae and monoisotopic masses and then rank-ordering of the hits using appropriate relevance criteria. The most li...

  19. Applied gamma-ray spectrometry

    Dams, R; Crouthamel, Carl E

    1970-01-01

    Applied Gamma-Ray Spectrometry covers real life application of the gamma-ray and the devices used in their experimental studies. This book is organized into 9 chapters, and starts with discussions of the various decay processes, the possible interaction mechanisms of gamma radiation with matter, and the intrinsic and extrinsic variables, which affect the observed gamma-ray and X-ray spectra. The subsequent chapters deal with the properties and fabrication of scintillation detectors, semiconductor detectors, and proportional gas counters. These chapters present some of the most widely utilized

  20. Mass spectrometry. [review of techniques

    Burlingame, A. L.; Kimble, B. J.; Derrick, P. J.

    1976-01-01

    Advances in mass spectrometry (MS) and its applications over the past decade are reviewed in depth, with annotated literature references. New instrumentation and techniques surveyed include: modulated-beam MS, chromatographic MS on-line computer techniques, digital computer-compatible quadrupole MS, selected ion monitoring (mass fragmentography), and computer-aided management of MS data and interpretation. Areas of application surveyed include: organic MS and electron impact MS, field ionization kinetics, appearance potentials, translational energy release, studies of metastable species, photoionization, calculations of molecular orbitals, chemical kinetics, field desorption MS, high pressure MS, ion cyclotron resonance, biochemistry, medical/clinical chemistry, pharmacology, and environmental chemistry and pollution studies.

  1. Deuterium measurement by emission spectrometry

    Niemann, E.G.; Heilig, K.; Dumke, I.

    1978-01-01

    The method makes it possible to determine the relative deuterium content of enriched water samples. For this, the relative intensities of the Hα and Dα lines are measured which are emitted by a high-frequency discharge in water vapour. Although the method is not as exact as mass spectrometry, it has the following advantages: - Easy sample preparation (no reduction necessary); - samples of highly different enrichment can be measured one after the other without the danger of memory effects; - much lower apparatus and cost expenditure. The necessary sample size is about the same in both methods. (orig.) [de

  2. Functional genomics by mass spectrometry

    Andersen, Jens S.; Mann, M

    2000-01-01

    Systematic analysis of the function of genes can take place at the oligonucleotide or protein level. The latter has the advantage of being closest to function, since it is proteins that perform most of the reactions necessary for the cell. For most protein based ('proteomic') approaches to gene f...... numbers of intact proteins by mass spectrometry directly. Examples from this laboratory illustrate biological problem solving by modern mass spectrometric techniques. These include the analysis of the structure and function of the nucleolus and the analysis of signaling complexes....

  3. Principle of accelerator mass spectrometry

    Matsuzaki, Hiroyuki

    2007-01-01

    The principle of accelerator mass spectrometry (AMS) is described mainly on technical aspects: hardware construction of AMS, measurement of isotope ratio, sensitivity of measurement (measuring limit), measuring accuracy, and application of data. The content may be summarized as follows: rare isotope (often long-lived radioactive isotope) can be detected by various use of the ion energy obtained by the acceleration of ions, a measurable isotope ratio is one of rare isotope to abundant isotopes, and a measured value of isotope ratio is uncertainty to true one. Such a fact must be kept in mind on the use of AMS data to application research. (M.H.)

  4. Role of Mass Spectrometry in Clinical Endocrinology.

    Ketha, Siva S; Singh, Ravinder J; Ketha, Hemamalini

    2017-09-01

    The advent of mass spectrometry into the clinical laboratory has led to an improvement in clinical management of several endocrine diseases. Liquid chromatography tandem mass spectrometry found some of its first clinical applications in the diagnosis of inborn errors of metabolism, in quantitative steroid analysis, and in drug analysis laboratories. Mass spectrometry assays offer analytical sensitivity and specificity that is superior to immunoassays for many analytes. This article highlights several areas of clinical endocrinology that have witnessed the use of liquid chromatography tandem mass spectrometry to improve clinical outcomes. Copyright © 2017 Elsevier Inc. All rights reserved.

  5. Tandem mass spectrometry: analysis of complex mixtures

    Singleton, K.E.

    1985-01-01

    Applications of tandem mass spectrometry (MS/MS) for the analysis of complex mixtures results in increased specificity and selectivity by using a variety of reagent gases in both negative and positive ion modes. Natural isotopic abundance ratios were examined in both simple and complex mixtures using parent, daughter and neutral loss scans. MS/MS was also used to discover new compounds. Daughter scans were used to identify seven new alkaloids in a cactus species. Three of these alkaloids were novel compounds, and included the first simple, fully aromatic isoquinoline alkaloids reported in Cactaceae. MS/MS was used to characterize the chemical reaction products of coal in studies designed to probe its macromolecular structure. Negative ion chemical ionization was utilized to study reaction products resulting from the oxidation of coal. Possible structural units in the precursor coal were predicted based on the reaction products identified, aliphatic and aromatic acids and their anhydrides. The MS/MS method was also used to characterize reaction products resulting from coal liquefaction and/or extraction. These studies illustrate the types of problems for which MS/MS is useful. Emphasis has been placed on characterization of complex mixtures by selecting experimental parameters which enhance the information obtained. The value of using MS/MS in conjunction with other analytical techniques as well as the chemical pretreatment is demonstrated

  6. Quantitative mass spectrometry: an overview

    Urban, Pawel L.

    2016-10-01

    Mass spectrometry (MS) is a mainstream chemical analysis technique in the twenty-first century. It has contributed to numerous discoveries in chemistry, physics and biochemistry. Hundreds of research laboratories scattered all over the world use MS every day to investigate fundamental phenomena on the molecular level. MS is also widely used by industry-especially in drug discovery, quality control and food safety protocols. In some cases, mass spectrometers are indispensable and irreplaceable by any other metrological tools. The uniqueness of MS is due to the fact that it enables direct identification of molecules based on the mass-to-charge ratios as well as fragmentation patterns. Thus, for several decades now, MS has been used in qualitative chemical analysis. To address the pressing need for quantitative molecular measurements, a number of laboratories focused on technological and methodological improvements that could render MS a fully quantitative metrological platform. In this theme issue, the experts working for some of those laboratories share their knowledge and enthusiasm about quantitative MS. I hope this theme issue will benefit readers, and foster fundamental and applied research based on quantitative MS measurements. This article is part of the themed issue 'Quantitative mass spectrometry'.

  7. Mass Spectrometry Applications for Toxicology.

    Mbughuni, Michael M; Jannetto, Paul J; Langman, Loralie J

    2016-12-01

    Toxicology is a multidisciplinary study of poisons, aimed to correlate the quantitative and qualitative relationships between poisons and their physiological and behavioural effects in living systems. Other key aspects of toxicology focus on elucidation of the mechanisms of action of poisons and development of remedies and treatment plans for associated toxic effects. In these endeavours, Mass spectrometry (MS) has become a powerful analytical technique with a wide range of application used in the Toxicological analysis of drugs, poisons, and metabolites of both. To date, MS applications have permeated all fields of toxicology which include; environmental, clinical, and forensic toxicology. While many different analytical applications are used in these fields, MS and its hyphenated applications such as; gas chromatography MS (GC-MS), liquid chromatography MS (LC-MS), inductively coupled plasma ionization MS (ICP-MS), tandem mass spectrometry (MS/MS and MS n ) have emerged as powerful tools used in toxicology laboratories. This review will focus on these hyphenated MS technologies and their applications for toxicology.

  8. Mass Spectrometry Applications for Toxicology

    Mbughuni, Michael M.; Jannetto, Paul J.

    2016-01-01

    Toxicology is a multidisciplinary study of poisons, aimed to correlate the quantitative and qualitative relationships between poisons and their physiological and behavioural effects in living systems. Other key aspects of toxicology focus on elucidation of the mechanisms of action of poisons and development of remedies and treatment plans for associated toxic effects. In these endeavours, Mass spectrometry (MS) has become a powerful analytical technique with a wide range of application used in the Toxicological analysis of drugs, poisons, and metabolites of both. To date, MS applications have permeated all fields of toxicology which include; environmental, clinical, and forensic toxicology. While many different analytical applications are used in these fields, MS and its hyphenated applications such as; gas chromatography MS (GC-MS), liquid chromatography MS (LC-MS), inductively coupled plasma ionization MS (ICP-MS), tandem mass spectrometry (MS/MS and MSn) have emerged as powerful tools used in toxicology laboratories. This review will focus on these hyphenated MS technologies and their applications for toxicology. PMID:28149262

  9. Imaging and mapping of mouse bone using MALDI-imaging mass spectrometry

    Yoko Fujino

    2016-12-01

    Full Text Available Matrix-assisted laser desorption/ionization-imaging mass spectrometry (MALDI-IMS is an advanced method used globally to analyze the distribution of biomolecules on tissue cryosections without any probes. In bones, however, hydroxyapatite crystals make it difficult to determine the distribution of biomolecules using MALDI-IMS. Additionally, there is limited information regarding the use of this method to analyze bone tissues. To determine whether MALDI-IMS analysis of bone tissues can facilitate comprehensive mapping of biomolecules in mouse bone, we first dissected femurs and tibiae from 8-week-old male mice and characterized the quality of multiple fixation and decalcification methods for preparation of the samples. Cryosections were mounted on indium tin oxide-coated glass slides, dried, and then a matrix solution was sprayed on the tissue surface. Images were acquired using an iMScope at a mass-to-charge range of 100–1000. Hematoxylin-eosin, Alcian blue, Azan, and periodic acid-Schiff staining of adjacent sections was used to evaluate histological and histochemical features. Among the various fixation and decalcification conditions, sections from trichloroacetic acid-treated samples were most suitable to examine both histology and comprehensive MS images. However, histotypic MS signals were detected in all sections. In addition to the MS images, phosphocholine was identified as a candidate metabolite. These results indicate successful detection of biomolecules in bone using MALDI-IMS. Although analytical procedures and compositional adjustment regarding the performance of the device still require further development, IMS appears to be a powerful tool to determine the distribution of biomolecules in bone tissues. Keywords: Matrix-assisted laser desorption/ionization-imaging mass spectrometry, Tissue cryosection, Bone, Fixation, Decalcification

  10. Thoughts on identifiers

    CERN. Geneva

    2005-01-01

    As business processes and information transactions have become an inextricably intertwined with the Web, the importance of assignment, registration, discovery, and maintenance of identifiers has increased. In spite of this, integrated frameworks for managing identifiers have been slow to emerge. Instead, identification systems arise (quite naturally) from immediate business needs without consideration for how they fit into larger information architectures. In addition, many legacy identifier systems further complicate the landscape, making it difficult for content managers to select and deploy identifier systems that meet both the business case and long term information management objectives. This presentation will outline a model for evaluating identifier applications and the functional requirements of the systems necessary to support them. The model is based on a layered analysis of the characteristics of identifier systems, including: * Functional characteristics * Technology * Policy * Business * Social T...

  11. Simultaneous identification of abused drugs, benzodiazepines, and new psychoactive substances in urine by liquid chromatography tandem mass spectrometry

    Hei-Hwa Lee

    2016-03-01

    Full Text Available A literature search reveals no studies concerning simultaneous identification of commonly abused drugs, benzodiazepines, and new psychoactive substances in urine by liquid chromatography tandem mass spectrometry (LC–MS/MS. We developed and validated an LC–MS/MS method for simultaneous identification of multiple abused drugs, benzodiazepines, and new psychoactive substances in urine from suspected drug abusers. The instrument was operated in multiple-reaction monitoring using an electrospray ionization mode. Chromatograms were separated using an ACE5 C18 column on a gradient of acetonitrile. After liquid–liquid extraction, samples were passed through a 0.22-μm polyvinylidene difluoride filter before injection into the LC–MS/MS. The limits of quantitation ranged from 0.5 ng/mL to 31.3 ng/mL. The linearity ranged from 0.5 ng/mL to 200 ng/mL. The precision results were below 15.4% (intraday and 18.7% (interday. The intraday accuracy ranged from 85.9% to 121.0%; interday accuracy ranged from 66.1% to 128.7%. The proposed method was applied to 769 urine samples. The most common three drugs identified were ketamine, amphetamine, and opiates. The drug positive rate for one or more drugs was 79.6%. Our results demonstrate the suitability of the LC–MS/MS method for simultaneous identification of multiple abused drugs, benzodiazepines, and new psychoactive substances in urine.

  12. Identifiability in stochastic models

    1992-01-01

    The problem of identifiability is basic to all statistical methods and data analysis, occurring in such diverse areas as Reliability Theory, Survival Analysis, and Econometrics, where stochastic modeling is widely used. Mathematics dealing with identifiability per se is closely related to the so-called branch of ""characterization problems"" in Probability Theory. This book brings together relevant material on identifiability as it occurs in these diverse fields.

  13. Surface-Confined Aqueous Reversible Addition-Fragmentation Chain Transfer (SCARAFT) Polymerization Method for Preparation of Coated Capillary Leads to over 10 000 Peptides Identified from 25 ng HeLa Digest by Using Capillary Zone Electrophoresis-Tandem Mass Spectrometry.

    Zhang, Zhenbin; Peuchen, Elizabeth H; Dovichi, Norman J

    2017-06-20

    A surface-confined aqueous reversible addition-fragmentation chain transfer (SCARAFT) polymerization method was developed to coat capillaries for use in capillary zone electrophoresis (CZE). SCARAFT polymerization primarily takes place on the inner surface of the capillary instead of in solution, which greatly improves the homogeneity of the coating. Capillaries treated with this coating produced an electroosmotic mobility of 2.8 ± 0.2 × 10 -6 cm 2 ·V -1 ·s -1 (N = 3), which is roughly an order of magnitude lower than that of commercial linear polyacrylamide (LPA)-coated capillaries. Coated capillaries were evaluated for bottom-up proteomic analysis using CZE. The very low electroosmotic mobility results in a 200 min separation and improved single-shot analysis. An average of 977 protein groups and 5605 unique peptides were identified from 50 ng of an E. coli digest, and 2158 protein groups and 10 005 peptides were identified from 25 ng of a HeLa digest using single-shot analysis with a SCARAFT-acrylamide capillary coupled to a Q Exactive HF mass spectrometer. The coating is stable. A single capillary was used for over 200 h (8.4 days) of continuous operation. RSD in migration time was between 2 and 3% for selected ion electropherograms (SIEs) generated for six ions; median theoretical plate counts ranged from 240 000 to 600 000 for these SIEs. Various types of coatings could be prepared by simply changing the functional vinyl monomers in the polymerization mixture. Positively charged coatings using direct attachment and formation of a block copolymer were prepared and demonstrated for the separation of mixtures of intact proteins.

  14. T cells recognizing a peptide contaminant undetectable by mass spectrometry

    Brezar, Vedran; Culina, Slobodan; Østerbye, Thomas

    2011-01-01

    Synthetic peptides are widely used in immunological research as epitopes to stimulate their cognate T cells. These preparations are never completely pure, but trace contaminants are commonly revealed by mass spectrometry quality controls. In an effort to characterize novel major histocompatibility...... complex (MHC) Class I-restricted ß-cell epitopes in non-obese diabetic (NOD) mice, we identified islet-infiltrating CD8+ T cells recognizing a contaminating peptide. The amount of this contaminant was so small to be undetectable by direct mass spectrometry. Only after concentration by liquid...... chromatography, we observed a mass peak corresponding to an immunodominant islet-specific glucose-6-phosphatase catalytic subunit-related protein (IGRP)(206-214) epitope described in the literature. Generation of CD8+ T-cell clones recognizing IGRP(206-214) using a novel method confirmed the identity...

  15. Sharing and community curation of mass spectrometry data with GNPS

    Nguyen, Don Duy; Watrous, Jeramie; Kapono, Clifford A; Luzzatto-Knaan, Tal; Porto, Carla; Bouslimani, Amina; Melnik, Alexey V; Meehan, Michael J; Liu, Wei-Ting; Crüsemann, Max; Boudreau, Paul D; Esquenazi, Eduardo; Sandoval-Calderón, Mario; Kersten, Roland D; Pace, Laura A; Quinn, Robert A; Duncan, Katherine R; Hsu, Cheng-Chih; Floros, Dimitrios J; Gavilan, Ronnie G; Kleigrewe, Karin; Northen, Trent; Dutton, Rachel J; Parrot, Delphine; Carlson, Erin E; Aigle, Bertrand; Michelsen, Charlotte F; Jelsbak, Lars; Sohlenkamp, Christian; Pevzner, Pavel; Edlund, Anna; McLean, Jeffrey; Piel, Jörn; Murphy, Brian T; Gerwick, Lena; Liaw, Chih-Chuang; Yang, Yu-Liang; Humpf, Hans-Ulrich; Maansson, Maria; Keyzers, Robert A; Sims, Amy C; Johnson, Andrew R.; Sidebottom, Ashley M; Sedio, Brian E; Klitgaard, Andreas; Larson, Charles B; P., Cristopher A Boya; Torres-Mendoza, Daniel; Gonzalez, David J; Silva, Denise B; Marques, Lucas M; Demarque, Daniel P; Pociute, Egle; O'Neill, Ellis C; Briand, Enora; Helfrich, Eric J. N.; Granatosky, Eve A; Glukhov, Evgenia; Ryffel, Florian; Houson, Hailey; Mohimani, Hosein; Kharbush, Jenan J; Zeng, Yi; Vorholt, Julia A; Kurita, Kenji L; Charusanti, Pep; McPhail, Kerry L; Nielsen, Kristian Fog; Vuong, Lisa; Elfeki, Maryam; Traxler, Matthew F; Engene, Niclas; Koyama, Nobuhiro; Vining, Oliver B; Baric, Ralph; Silva, Ricardo R; Mascuch, Samantha J; Tomasi, Sophie; Jenkins, Stefan; Macherla, Venkat; Hoffman, Thomas; Agarwal, Vinayak; Williams, Philip G; Dai, Jingqui; Neupane, Ram; Gurr, Joshua; Rodríguez, Andrés M. C.; Lamsa, Anne; Zhang, Chen; Dorrestein, Kathleen; Duggan, Brendan M; Almaliti, Jehad; Allard, Pierre-Marie; Phapale, Prasad; Nothias, Louis-Felix; Alexandrov, Theodore; Litaudon, Marc; Wolfender, Jean-Luc; Kyle, Jennifer E; Metz, Thomas O; Peryea, Tyler; Nguyen, Dac-Trung; VanLeer, Danielle; Shinn, Paul; Jadhav, Ajit; Müller, Rolf; Waters, Katrina M; Shi, Wenyuan; Liu, Xueting; Zhang, Lixin; Knight, Rob; Jensen, Paul R; Palsson, Bernhard O; Pogliano, Kit; Linington, Roger G; Gutiérrez, Marcelino; Lopes, Norberto P; Gerwick, William H; Moore, Bradley S; Dorrestein, Pieter C; Bandeira, Nuno

    2017-01-01

    The potential of the diverse chemistries present in natural products (NP) for biotechnology and medicine remains untapped because NP databases are not searchable with raw data and the NP community has no way to share data other than in published papers. Although mass spectrometry techniques are well-suited to high-throughput characterization of natural products, there is a pressing need for an infrastructure to enable sharing and curation of data. We present Global Natural Products Social molecular networking (GNPS, http://gnps.ucsd.edu), an open-access knowledge base for community wide organization and sharing of raw, processed or identified tandem mass (MS/MS) spectrometry data. In GNPS crowdsourced curation of freely available community-wide reference MS libraries will underpin improved annotations. Data-driven social-networking should facilitate identification of spectra and foster collaborations. We also introduce the concept of ‘living data’ through continuous reanalysis of deposited data. PMID:27504778

  16. MALDI-TOF mass spectrometry for early identification of bacteria grown in blood culture bottles.

    Zabbe, Jean-Benoît; Zanardo, Laura; Mégraud, Francis; Bessède, Emilie

    2015-08-01

    This note reports an interesting way to rapidly identify bacteria grown from blood culture bottles. Chocolate agar plates were inoculated with 1 drop of the positive blood bottle medium. After a 3-hour incubation, the growth veil was submitted to MALDI-TOF mass spectrometry: 77% of the bacteria present have been correctly identified. Copyright © 2015 Elsevier B.V. All rights reserved.

  17. Mass spectrometry in grape and wine chemistry. Part II: The consumer protection.