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Sample records for targeted proteomics experiments

  1. Efficient visualization of high-throughput targeted proteomics experiments: TAPIR.

    Science.gov (United States)

    Röst, Hannes L; Rosenberger, George; Aebersold, Ruedi; Malmström, Lars

    2015-07-15

    Targeted mass spectrometry comprises a set of powerful methods to obtain accurate and consistent protein quantification in complex samples. To fully exploit these techniques, a cross-platform and open-source software stack based on standardized data exchange formats is required. We present TAPIR, a fast and efficient Python visualization software for chromatograms and peaks identified in targeted proteomics experiments. The input formats are open, community-driven standardized data formats (mzML for raw data storage and TraML encoding the hierarchical relationships between transitions, peptides and proteins). TAPIR is scalable to proteome-wide targeted proteomics studies (as enabled by SWATH-MS), allowing researchers to visualize high-throughput datasets. The framework integrates well with existing automated analysis pipelines and can be extended beyond targeted proteomics to other types of analyses. TAPIR is available for all computing platforms under the 3-clause BSD license at https://github.com/msproteomicstools/msproteomicstools. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  2. Skyline: an open source document editor for creating and analyzing targeted proteomics experiments.

    Science.gov (United States)

    MacLean, Brendan; Tomazela, Daniela M; Shulman, Nicholas; Chambers, Matthew; Finney, Gregory L; Frewen, Barbara; Kern, Randall; Tabb, David L; Liebler, Daniel C; MacCoss, Michael J

    2010-04-01

    Skyline is a Windows client application for targeted proteomics method creation and quantitative data analysis. It is open source and freely available for academic and commercial use. The Skyline user interface simplifies the development of mass spectrometer methods and the analysis of data from targeted proteomics experiments performed using selected reaction monitoring (SRM). Skyline supports using and creating MS/MS spectral libraries from a wide variety of sources to choose SRM filters and verify results based on previously observed ion trap data. Skyline exports transition lists to and imports the native output files from Agilent, Applied Biosystems, Thermo Fisher Scientific and Waters triple quadrupole instruments, seamlessly connecting mass spectrometer output back to the experimental design document. The fast and compact Skyline file format is easily shared, even for experiments requiring many sample injections. A rich array of graphs displays results and provides powerful tools for inspecting data integrity as data are acquired, helping instrument operators to identify problems early. The Skyline dynamic report designer exports tabular data from the Skyline document model for in-depth analysis with common statistical tools. Single-click, self-updating web installation is available at http://proteome.gs.washington.edu/software/skyline. This web site also provides access to instructional videos, a support board, an issues list and a link to the source code project.

  3. Panorama: a targeted proteomics knowledge base.

    Science.gov (United States)

    Sharma, Vagisha; Eckels, Josh; Taylor, Greg K; Shulman, Nicholas J; Stergachis, Andrew B; Joyner, Shannon A; Yan, Ping; Whiteaker, Jeffrey R; Halusa, Goran N; Schilling, Birgit; Gibson, Bradford W; Colangelo, Christopher M; Paulovich, Amanda G; Carr, Steven A; Jaffe, Jacob D; MacCoss, Michael J; MacLean, Brendan

    2014-09-05

    Panorama is a web application for storing, sharing, analyzing, and reusing targeted assays created and refined with Skyline,1 an increasingly popular Windows client software tool for targeted proteomics experiments. Panorama allows laboratories to store and organize curated results contained in Skyline documents with fine-grained permissions, which facilitates distributed collaboration and secure sharing of published and unpublished data via a web-browser interface. It is fully integrated with the Skyline workflow and supports publishing a document directly to a Panorama server from the Skyline user interface. Panorama captures the complete Skyline document information content in a relational database schema. Curated results published to Panorama can be aggregated and exported as chromatogram libraries. These libraries can be used in Skyline to pick optimal targets in new experiments and to validate peak identification of target peptides. Panorama is open-source and freely available. It is distributed as part of LabKey Server,2 an open source biomedical research data management system. Laboratories and organizations can set up Panorama locally by downloading and installing the software on their own servers. They can also request freely hosted projects on https://panoramaweb.org , a Panorama server maintained by the Department of Genome Sciences at the University of Washington.

  4. ExSTA: External Standard Addition Method for Accurate High-Throughput Quantitation in Targeted Proteomics Experiments.

    Science.gov (United States)

    Mohammed, Yassene; Pan, Jingxi; Zhang, Suping; Han, Jun; Borchers, Christoph H

    2018-03-01

    Targeted proteomics using MRM with stable-isotope-labeled internal-standard (SIS) peptides is the current method of choice for protein quantitation in complex biological matrices. Better quantitation can be achieved with the internal standard-addition method, where successive increments of synthesized natural form (NAT) of the endogenous analyte are added to each sample, a response curve is generated, and the endogenous concentration is determined at the x-intercept. Internal NAT-addition, however, requires multiple analyses of each sample, resulting in increased sample consumption and analysis time. To compare the following three methods, an MRM assay for 34 high-to-moderate abundance human plasma proteins is used: classical internal SIS-addition, internal NAT-addition, and external NAT-addition-generated in buffer using NAT and SIS peptides. Using endogenous-free chicken plasma, the accuracy is also evaluated. The internal NAT-addition outperforms the other two in precision and accuracy. However, the curves derived by internal vs. external NAT-addition differ by only ≈3.8% in slope, providing comparable accuracies and precision with good CV values. While the internal NAT-addition method may be "ideal", this new external NAT-addition can be used to determine the concentration of high-to-moderate abundance endogenous plasma proteins, providing a robust and cost-effective alternative for clinical analyses or other high-throughput applications. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  5. Halobacterium salinarum NRC-1 PeptideAtlas: toward strategies for targeted proteomics and improved proteome coverage.

    Science.gov (United States)

    Van, Phu T; Schmid, Amy K; King, Nichole L; Kaur, Amardeep; Pan, Min; Whitehead, Kenia; Koide, Tie; Facciotti, Marc T; Goo, Young Ah; Deutsch, Eric W; Reiss, David J; Mallick, Parag; Baliga, Nitin S

    2008-09-01

    The relatively small numbers of proteins and fewer possible post-translational modifications in microbes provide a unique opportunity to comprehensively characterize their dynamic proteomes. We have constructed a PeptideAtlas (PA) covering 62.7% of the predicted proteome of the extremely halophilic archaeon Halobacterium salinarum NRC-1 by compiling approximately 636 000 tandem mass spectra from 497 mass spectrometry runs in 88 experiments. Analysis of the PA with respect to biophysical properties of constituent peptides, functional properties of parent proteins of detected peptides, and performance of different mass spectrometry approaches has highlighted plausible strategies for improving proteome coverage and selecting signature peptides for targeted proteomics. Notably, discovery of a significant correlation between absolute abundances of mRNAs and proteins has helped identify low abundance of proteins as the major limitation in peptide detection. Furthermore, we have discovered that iTRAQ labeling for quantitative proteomic analysis introduces a significant bias in peptide detection by mass spectrometry. Therefore, despite identifying at least one proteotypic peptide for almost all proteins in the PA, a context-dependent selection of proteotypic peptides appears to be the most effective approach for targeted proteomics.

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

    Science.gov (United States)

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

    2013-12-16

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

  7. Elucidation of cross-species proteomic effects in human and hominin bone proteome identification through a bioinformatics experiment.

    Science.gov (United States)

    Welker, F

    2018-02-20

    The study of ancient protein sequences is increasingly focused on the analysis of older samples, including those of ancient hominins. The analysis of such ancient proteomes thereby potentially suffers from "cross-species proteomic effects": the loss of peptide and protein identifications at increased evolutionary distances due to a larger number of protein sequence differences between the database sequence and the analyzed organism. Error-tolerant proteomic search algorithms should theoretically overcome this problem at both the peptide and protein level; however, this has not been demonstrated. If error-tolerant searches do not overcome the cross-species proteomic issue then there might be inherent biases in the identified proteomes. Here, a bioinformatics experiment is performed to test this using a set of modern human bone proteomes and three independent searches against sequence databases at increasing evolutionary distances: the human (0 Ma), chimpanzee (6-8 Ma) and orangutan (16-17 Ma) reference proteomes, respectively. Incorrectly suggested amino acid substitutions are absent when employing adequate filtering criteria for mutable Peptide Spectrum Matches (PSMs), but roughly half of the mutable PSMs were not recovered. As a result, peptide and protein identification rates are higher in error-tolerant mode compared to non-error-tolerant searches but did not recover protein identifications completely. Data indicates that peptide length and the number of mutations between the target and database sequences are the main factors influencing mutable PSM identification. The error-tolerant results suggest that the cross-species proteomics problem is not overcome at increasing evolutionary distances, even at the protein level. Peptide and protein loss has the potential to significantly impact divergence dating and proteome comparisons when using ancient samples as there is a bias towards the identification of conserved sequences and proteins. Effects are minimized

  8. Halobacterium salinarum NRC-1 PeptideAtlas: strategies for targeted proteomics

    Science.gov (United States)

    Van, Phu T.; Schmid, Amy K.; King, Nichole L.; Kaur, Amardeep; Pan, Min; Whitehead, Kenia; Koide, Tie; Facciotti, Marc T.; Goo, Young-Ah; Deutsch, Eric W.; Reiss, David J.; Mallick, Parag; Baliga, Nitin S.

    2009-01-01

    The relatively small numbers of proteins and fewer possible posttranslational modifications in microbes provides a unique opportunity to comprehensively characterize their dynamic proteomes. We have constructed a Peptide Atlas (PA) for 62.7% of the predicted proteome of the extremely halophilic archaeon Halobacterium salinarum NRC-1 by compiling approximately 636,000 tandem mass spectra from 497 mass spectrometry runs in 88 experiments. Analysis of the PA with respect to biophysical properties of constituent peptides, functional properties of parent proteins of detected peptides, and performance of different mass spectrometry approaches has helped highlight plausible strategies for improving proteome coverage and selecting signature peptides for targeted proteomics. Notably, discovery of a significant correlation between absolute abundances of mRNAs and proteins has helped identify low abundance of proteins as the major limitation in peptide detection. Furthermore we have discovered that iTRAQ labeling for quantitative proteomic analysis introduces a significant bias in peptide detection by mass spectrometry. Therefore, despite identifying at least one proteotypic peptide for almost all proteins in the PA, a context-dependent selection of proteotypic peptides appears to be the most effective approach for targeted proteomics. PMID:18652504

  9. Nova target experiments

    International Nuclear Information System (INIS)

    Drake, R.P.

    1985-11-01

    The Nova laser, at the Lawrence Livermore National Laboratory, provides unique opportunities for target experiments. It has unprecedented energy on target and significant flexibility. The paper presented by John Hunt described the capabilities and the status of Nova. This paper discusses plans for future experiments using Nova, and the present status of target experiments. We plan to perform high-quality physics experiments that exploit the unique capabilities of Nova. Because this is our goal, we are fielding an extensive array of well-characterized target diagnostics to measure the emissions from the target. The first section of this paper discusses the basic target diagnostics. We are also taking care to quantify the performance of the laser

  10. CPTAC Collaborates with Molecular & Cellular Proteomics to Address Reproducibility in Targeted Assay Development | Office of Cancer Clinical Proteomics Research

    Science.gov (United States)

    The journal Molecular & Cellular Proteomics (MCP), in collaboration with the Clinical Proteomic Tumor Analysis Consortium (CPTAC) of the National Cancer Institute (NCI), part of the National Institutes of Health, announce new guidelines and requirements for papers describing the development and application of targeted mass spectrometry measurements of peptides, modified peptides and proteins (Mol Cell Proteomics 2017; PMID: 28183812).  NCI’s participation is part of NIH’s overall effort to address the r

  11. In silico proteome analysis to facilitate proteomics experiments using mass spectrometry

    Directory of Open Access Journals (Sweden)

    Lindo Micheal

    2003-08-01

    Full Text Available Abstract Proteomics experiments typically involve protein or peptide separation steps coupled to the identification of many hundreds to thousands of peptides by mass spectrometry. Development of methodology and instrumentation in this field is proceeding rapidly, and effective software is needed to link the different stages of proteomic analysis. We have developed an application, proteogest, written in Perl that generates descriptive and statistical analyses of the biophysical properties of multiple (e.g. thousands protein sequences submitted by the user, for instance protein sequences inferred from the complete genome sequence of a model organism. The application also carries out in silico proteolytic digestion of the submitted proteomes, or subsets thereof, and the distribution of biophysical properties of the resulting peptides is presented. proteogest is customizable, the user being able to select many options, for instance the cleavage pattern of the digestion treatment or the presence of modifications to specific amino acid residues. We show how proteogest can be used to compare the proteomes and digested proteome products of model organisms, to examine the added complexity generated by modification of residues, and to facilitate the design of proteomics experiments for optimal representation of component proteins.

  12. Proteomics Core

    Data.gov (United States)

    Federal Laboratory Consortium — Proteomics Core is the central resource for mass spectrometry based proteomics within the NHLBI. The Core staff help collaborators design proteomics experiments in a...

  13. Supramolecular Affinity Chromatography for Methylation-Targeted Proteomics.

    Science.gov (United States)

    Garnett, Graham A E; Starke, Melissa J; Shaurya, Alok; Li, Janessa; Hof, Fraser

    2016-04-05

    Proteome-wide studies of post-translationally methylated species using mass spectrometry are complicated by high sample diversity, competition for ionization among peptides, and mass redundancies. Antibody-based enrichment has powered methylation proteomics until now, but the reliability, pan-specificity, polyclonal nature, and stability of the available pan-specific antibodies are problematic and do not provide a standard, reliable platform for investigators. We have invented an anionic supramolecular host that can form host-guest complexes selectively with methyllysine-containing peptides and used it to create a methylysine-affinity column. The column resolves peptides on the basis of methylation-a feat impossible with a comparable commercial cation-exchange column. A proteolyzed nuclear extract was separated on the methyl-affinity column prior to standard proteomics analysis. This experiment demonstrates that such chemical methyl-affinity columns are capable of enriching and improving the analysis of methyllysine residues from complex protein mixtures. We discuss the importance of this advance in the context of biomolecule-driven enrichment methods.

  14. Targeted proteomics as a tool for porcine acute phase proteins measurements

    DEFF Research Database (Denmark)

    Marco-Ramell, Anna; Bassols, Anna; Bislev, Stine Lønnerup

    2013-01-01

    . Selected reaction monitoring (SRM), a targeted quantitative proteomic technique, may be used as an alternative to commercial kits for the measurement and validation of target proteins. Acute phase proteins (APPs) are widely recognized inflammation and infection biomarkers (Eckersall, 2010...

  15. A Miniaturized Chemical Proteomic Approach for Target Profiling of Clinical Kinase Inhibitors in Tumor Biopsies

    Science.gov (United States)

    Chamrád, Ivo; Rix, Uwe; Stukalov, Alexey; Gridling, Manuela; Parapatics, Katja; Müller, André C.; Altiok, Soner; Colinge, Jacques; Superti-Furga, Giulio; Haura, Eric B.; Bennett, Keiryn L.

    2014-01-01

    While targeted therapy based on the idea of attenuating the activity of a preselected, therapeutically relevant protein has become one of the major trends in modern cancer therapy, no truly specific targeted drug has been developed and most clinical agents have displayed a degree of polypharmacology. Therefore, the specificity of anticancer therapeutics has emerged as a highly important but severely underestimated issue. Chemical proteomics is a powerful technique combining postgenomic drug-affinity chromatography with high-end mass spectrometry analysis and bioinformatic data processing to assemble a target profile of a desired therapeutic molecule. Due to high demands on the starting material, however, chemical proteomic studies have been mostly limited to cancer cell lines. Herein, we report a down-scaling of the technique to enable the analysis of very low abundance samples, as those obtained from needle biopsies. By a systematic investigation of several important parameters in pull-downs with the multikinase inhibitor bosutinib, the standard experimental protocol was optimized to 100 µg protein input. At this level, more than 30 well-known targets were detected per single pull-down replicate with high reproducibility. Moreover, as presented by the comprehensive target profile obtained from miniaturized pull-downs with another clinical drug, dasatinib, the optimized protocol seems to be extendable to other drugs of interest. Sixty distinct human and murine targets were finally identified for bosutinib and dasatinib in chemical proteomic experiments utilizing core needle biopsy samples from xenotransplants derived from patient tumor tissue. Altogether, the developed methodology proves robust and generic and holds many promises for the field of personalized health care. PMID:23901793

  16. Clinical proteomics-driven precision medicine for targeted cancer therapy: current overview and future perspectives.

    Science.gov (United States)

    Zhou, Li; Wang, Kui; Li, Qifu; Nice, Edouard C; Zhang, Haiyuan; Huang, Canhua

    2016-01-01

    Cancer is a common disease that is a leading cause of death worldwide. Currently, early detection and novel therapeutic strategies are urgently needed for more effective management of cancer. Importantly, protein profiling using clinical proteomic strategies, with spectacular sensitivity and precision, offer excellent promise for the identification of potential biomarkers that would direct the development of targeted therapeutic anticancer drugs for precision medicine. In particular, clinical sample sources, including tumor tissues and body fluids (blood, feces, urine and saliva), have been widely investigated using modern high-throughput mass spectrometry-based proteomic approaches combined with bioinformatic analysis, to pursue the possibilities of precision medicine for targeted cancer therapy. Discussed in this review are the current advantages and limitations of clinical proteomics, the available strategies of clinical proteomics for the management of precision medicine, as well as the challenges and future perspectives of clinical proteomics-driven precision medicine for targeted cancer therapy.

  17. Implementation of statistical process control for proteomic experiments via LC MS/MS.

    Science.gov (United States)

    Bereman, Michael S; Johnson, Richard; Bollinger, James; Boss, Yuval; Shulman, Nick; MacLean, Brendan; Hoofnagle, Andrew N; MacCoss, Michael J

    2014-04-01

    Statistical process control (SPC) is a robust set of tools that aids in the visualization, detection, and identification of assignable causes of variation in any process that creates products, services, or information. A tool has been developed termed Statistical Process Control in Proteomics (SProCoP) which implements aspects of SPC (e.g., control charts and Pareto analysis) into the Skyline proteomics software. It monitors five quality control metrics in a shotgun or targeted proteomic workflow. None of these metrics require peptide identification. The source code, written in the R statistical language, runs directly from the Skyline interface, which supports the use of raw data files from several of the mass spectrometry vendors. It provides real time evaluation of the chromatographic performance (e.g., retention time reproducibility, peak asymmetry, and resolution), and mass spectrometric performance (targeted peptide ion intensity and mass measurement accuracy for high resolving power instruments) via control charts. Thresholds are experiment- and instrument-specific and are determined empirically from user-defined quality control standards that enable the separation of random noise and systematic error. Finally, Pareto analysis provides a summary of performance metrics and guides the user to metrics with high variance. The utility of these charts to evaluate proteomic experiments is illustrated in two case studies.

  18. The Proteomics Big Challenge for Biomarkers and New Drug-Targets Discovery

    Science.gov (United States)

    Savino, Rocco; Paduano, Sergio; Preianò, Mariaimmacolata; Terracciano, Rosa

    2012-01-01

    In the modern process of drug discovery, clinical, functional and chemical proteomics can converge and integrate synergies. Functional proteomics explores and elucidates the components of pathways and their interactions which, when deregulated, lead to a disease condition. This knowledge allows the design of strategies to target multiple pathways with combinations of pathway-specific drugs, which might increase chances of success and reduce the occurrence of drug resistance. Chemical proteomics, by analyzing the drug interactome, strongly contributes to accelerate the process of new druggable targets discovery. In the research area of clinical proteomics, proteome and peptidome mass spectrometry-profiling of human bodily fluid (plasma, serum, urine and so on), as well as of tissue and of cells, represents a promising tool for novel biomarker and eventually new druggable targets discovery. In the present review we provide a survey of current strategies of functional, chemical and clinical proteomics. Major issues will be presented for proteomic technologies used for the discovery of biomarkers for early disease diagnosis and identification of new drug targets. PMID:23203042

  19. From protein catalogues towards targeted proteomics approaches in cereal grains

    DEFF Research Database (Denmark)

    Finnie, Christine; Sultan, Abida; Grasser, Klaus D.

    2011-01-01

    Due to their importance for human nutrition, the protein content of cereal grains has been a subject of intense study for over a century and cereal grains were not surprisingly one of the earliest subjects for 2D-gel-based proteome analysis. Over the last two decades, countless cereal grain prote...

  20. Elucidation of cross-species proteomic effects in human and hominin bone proteome identification through a bioinformatics experiment

    DEFF Research Database (Denmark)

    Welker, F.

    2018-01-01

    Background: The study of ancient protein sequences is increasingly focused on the analysis of older samples, including those of ancient hominins. The analysis of such ancient proteomes thereby potentially suffers from "cross-species proteomic effects": the loss of peptide and protein identificati......Background: The study of ancient protein sequences is increasingly focused on the analysis of older samples, including those of ancient hominins. The analysis of such ancient proteomes thereby potentially suffers from "cross-species proteomic effects": the loss of peptide and protein...... not been demonstrated. If error-tolerant searches do not overcome the cross-species proteomic issue then there might be inherent biases in the identified proteomes. Here, a bioinformatics experiment is performed to test this using a set of modern human bone proteomes and three independent searches against......), but roughly half of the mutable PSMs were not recovered. As a result, peptide and protein identification rates are higher in error-tolerant mode compared to non-error-tolerant searches but did not recover protein identifications completely. Data indicates that peptide length and the number of mutations...

  1. Target identification of natural and traditional medicines with quantitative chemical proteomics approaches.

    Science.gov (United States)

    Wang, Jigang; Gao, Liqian; Lee, Yew Mun; Kalesh, Karunakaran A; Ong, Yong Siang; Lim, Jaehong; Jee, Joo-Eun; Sun, Hongyan; Lee, Su Seong; Hua, Zi-Chun; Lin, Qingsong

    2016-06-01

    Natural and traditional medicines, being a great source of drugs and drug leads, have regained wide interests due to the limited success of high-throughput screening of compound libraries in the past few decades and the recent technology advancement. Many drugs/bioactive compounds exert their functions through interaction with their protein targets, with more and more drugs showing their ability to target multiple proteins, thus target identification has an important role in drug discovery and biomedical research fields. Identifying drug targets not only furthers the understanding of the mechanism of action (MOA) of a drug but also reveals its potential therapeutic applications and adverse side effects. Chemical proteomics makes use of affinity chromatography approaches coupled with mass spectrometry to systematically identify small molecule-protein interactions. Although traditional affinity-based chemical proteomics approaches have made great progress in the identification of cellular targets and elucidation of MOAs of many bioactive molecules, nonspecific binding remains a major issue which may reduce the accuracy of target identification and may hamper the drug development process. Recently, quantitative proteomics approaches, namely, metabolic labeling, chemical labeling, or label-free approaches, have been implemented in target identification to overcome such limitations. In this review, we will summarize and discuss the recent advances in the application of various quantitative chemical proteomics approaches for the identification of targets of natural and traditional medicines. Copyright © 2016. Published by Elsevier Inc.

  2. Advances in the proteomic discovery of novel therapeutic targets in cancer

    Directory of Open Access Journals (Sweden)

    Guo S

    2013-10-01

    Full Text Available Shanchun Guo,1 Jin Zou,2 Guangdi Wang3 1Department of Microbiology, Biochemistry, and Immunology, Morehouse School of Medicine, 2Center for Cancer Research and Therapeutic Development, Clark Atlanta University, Atlanta, GA, USA; 3Research Centers in Minority Institutions Cancer Research Program, Xavier University of Louisiana, New Orleans, LA, USA Abstract: Proteomic approaches are continuing to make headways in cancer research by helping to elucidate complex signaling networks that underlie tumorigenesis and disease progression. This review describes recent advances made in the proteomic discovery of drug targets for therapeutic development. A variety of technical and methodological advances are overviewed with a critical assessment of challenges and potentials. A number of potential drug targets, such as baculoviral inhibitor of apoptosis protein repeat-containing protein 6, macrophage inhibitory cytokine 1, phosphoglycerate mutase 1, prohibitin 1, fascin, and pyruvate kinase isozyme 2 were identified in the proteomic analysis of drug-resistant cancer cells, drug action, and differential disease state tissues. Future directions for proteomics-based target identification and validation to be more translation efficient are also discussed. Keywords: proteomics, cancer, therapeutic target, signaling network, tumorigenesis

  3. Quantitative targeted proteomics for understanding the blood-brain barrier: towards pharmacoproteomics.

    Science.gov (United States)

    Ohtsuki, Sumio; Hirayama, Mio; Ito, Shingo; Uchida, Yasuo; Tachikawa, Masanori; Terasaki, Tetsuya

    2014-06-01

    The blood-brain barrier (BBB) is formed by brain capillary endothelial cells linked together via complex tight junctions, and serves to prevent entry of drugs into the brain. Multiple transporters are expressed at the BBB, where they control exchange of materials between the circulating blood and brain interstitial fluid, thereby supporting and protecting the CNS. An understanding of the BBB is necessary for efficient development of CNS-acting drugs and to identify potential drug targets for treatment of CNS diseases. Quantitative targeted proteomics can provide detailed information on protein expression levels at the BBB. The present review highlights the latest applications of quantitative targeted proteomics in BBB research, specifically to evaluate species and in vivo-in vitro differences, and to reconstruct in vivo transport activity. Such a BBB quantitative proteomics approach can be considered as pharmacoproteomics.

  4. Enhancing cognate target elution efficiency in gel-free chemical proteomics

    Directory of Open Access Journals (Sweden)

    Branka Radic-Sarikas

    2015-12-01

    Full Text Available Gel-free liquid chromatography mass spectrometry coupled to chemical proteomics is a powerful approach for characterizing cellular target profiles of small molecules. We have previously described a fast and efficient elution protocol; however, altered target profiles were observed. We hypothesised that elution conditions critically impact the effectiveness of disrupting drug-protein interactions. Thus, a number of elution conditions were systematically assessed with the aim of improving the recovery of all classes of proteins whilst maintaining compatibility with immunoblotting procedures. A double elution with formic acid combined with urea emerged as the most efficient and generically applicable elution method for chemical proteomics

  5. The Scottish Structural Proteomics Facility: targets, methods and outputs

    DEFF Research Database (Denmark)

    Oke, Muse; Carter, Lester G; Johnson, Kenneth A

    2010-01-01

    The Scottish Structural Proteomics Facility was funded to develop a laboratory scale approach to high throughput structure determination. The effort was successful in that over 40 structures were determined. These structures and the methods harnessed to obtain them are reported here. This report...... reflects on the value of automation but also on the continued requirement for a high degree of scientific and technical expertise. The efficiency of the process poses challenges to the current paradigm of structural analysis and publication. In the 5 year period we published ten peer-reviewed papers...

  6. Proteomic Identification of Non-Gal Antibody Targets After Pig-to-Primate Cardiac Xenotransplantation

    Science.gov (United States)

    Byrne, Guerard W.; Stalboerger, Paul G.; Davila, Eduardo; Heppelmann, Carrie J.; Gazi, Mozammel H.; McGregor, Hugh C. J.; LaBreche, Peter T.; Davies, William R.; Rao, Vinay P.; Oi, Keiji; Tazelaar, Henry D.; Logan, John S.; McGregor, Christopher G. A.

    2008-01-01

    Background Experience with non-antigenic galactose α1,3 galactose (αGal) polymers and development of αGal deficient pigs has reduced or eliminated the significance of this antigen in xenograft rejection. Despite these advances, delayed xenograft rejection (DXR) continues to occur most likely due to antibody responses to non-Gal endothelial cell (EC) antigens. Methods To gauge the diversity of the non-Gal antibody response we used antibody derived from CD46 transgenic heterotopic cardiac xenografts performed without T-cell immunosuppression, Group A (n = 4) and Gal knockout (GT-KO) heart transplants under tacrolimus and sirolimus immunosuppression, Group B (n = 8). Non-Gal antibody was measured by flow cytometry and by Western blots using GT-KO EC membrane antigens. A nanoLC/MS/MS analysis of proteins recovered from 2D gels was used to identify target antigens. Results Group A recipients exhibited a mixed cellular and humoral rejection. Group B recipients mainly exhibited classical DXR. Western blot analysis showed a non-Gal antibody response induced by GT+ and GT-KO hearts to an overlapping set of pig aortic EC membrane antigens. Proteomic analysis identified 14 potential target antigens but failed to define several immunodominant targets. Conclusions These experiments indicate that the non-Gal antibody response is directed to a number of stress response and inflammation related pig EC antigens and a few undefined targets. Further analysis of these antibody specificities using alternative methods is required to more fully define the repertoire of non-Gal antibody responses. PMID:18957049

  7. Differential proteomics of human seminal plasma: A potential target for searching male infertility marker proteins.

    Science.gov (United States)

    Tomar, Anil Kumar; Sooch, Balwinder Singh; Singh, Sarman; Yadav, Savita

    2012-04-01

    The clinical fertility tests, available in the market, fail to define the exact cause of male infertility in almost half of the cases and point toward a crucial need of developing better ways of infertility investigations. The protein biomarkers may help us toward better understanding of unknown cases of male infertility that, in turn, can guide us to find better therapeutic solutions. Many clinical attempts have been made to identify biomarkers of male infertility in sperm proteome but only few studies have targeted seminal plasma. Human seminal plasma is a rich source of proteins that are essentially required for development of sperm and successful fertilization. This viewpoint article highlights the importance of human seminal plasma proteome in reproductive physiology and suggests that differential proteomics integrated with functional analysis may help us in searching potential biomarkers of male infertility. © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  8. Targeted proteomics guided by label-free global proteome analysis in saliva reveal transition signatures from health to periodontal disease.

    Science.gov (United States)

    Bostanci, Nagihan; Selevsek, Nathalie; Wolski, Witold; Grossmann, Jonas; Bao, Kai; Wahlander, Asa; Trachsel, Christian; Schlapbach, Ralph; Özturk, Veli Özgen; Afacan, Beral; Emingil, Gulnur; Belibasakis, Georgios N

    2018-04-02

    Periodontal diseases are among the most prevalent worldwide, but largely silent, chronic diseases. They affect the tooth-supporting tissues with multiple ramifications on life quality. Their early diagnosis is still challenging, due to lack of appropriate molecular diagnostic methods. Saliva offers a non-invasively collectable reservoir of clinically relevant biomarkers, which, if utilized efficiently, could facilitate early diagnosis and monitoring of ongoing disease. Despite several novel protein markers being recently enlisted by discovery proteomics, their routine diagnostic application is hampered by the lack of validation platforms that allow for rapid, accurate and simultaneous quantification of multiple proteins in large cohorts. We carried out a pipeline of two proteomic platforms; firstly, we applied open ended label-free quantitative (LFQ) proteomics for discovery in saliva (n=67, health, gingivitis, and periodontitis), followed by selected-reaction monitoring (SRM)-targeted proteomics for validation in an independent cohort (n=82). The LFQ platform led to the discovery of 119 proteins with at least two-fold significant difference between health and disease. The 65 proteins chosen for the subsequent SRM platform included 50 related proteins derived from the significantly enriched processes of the LFQ data, 11 from literature-mining, and four house-keeping ones. Among those, 60 were reproducibly quantifiable proteins (92% success rate), represented by a total of 143 peptides. Machine-learning modeling led to a narrowed-down panel of five proteins of high predictive value for periodontal diseases (higher in disease: Matrix metalloproteinase-9, Ras-related protein-1, Actin-related protein 2/3 complex subunit 5; lower in disease: Clusterin, Deleted in Malignant Brain Tumors 1), with maximum area under the receiver operating curve >0.97. This panel enriches the pool of credible clinical biomarker candidates for diagnostic assay development. Yet, the quantum

  9. The OPERA experiment Target Tracker

    CERN Document Server

    Adam, T; Borer, K.; Campagne, Jean-Eric; Con-Sen, N.; de La Taille, C.; Dick, N.; Dracos, M.; Gaudiot, G.; Goeltzenlichter, T.; Gornushkin, Y.; Grapton, J.-N.; Guyonnet, J.-L.; Hess, M.; Igersheim, R.; Janicsko Csathy, J.; Jollet, C.; Juget, F.; Kocher, H.; Krasnoperov, A.; Krumstein, Z.; Martin-Chassard, G.; Moser, U.; Nozdrin, A.; Olchevski, A.; Porokhovoi, S.; Raux, L.; Sadovski, A.; Schuler, J.; Schutz, H.-U.; Schwab, C.; Smolnikov, A.; Van Beek, G.; Vilain, P.; Walchli, T.; Wilquet, G.; Wurtz, J.

    2007-01-01

    The main task of the Target Tracker detector of the long baseline neutrino oscillation OPERA experiment is to locate in which of the target elementary constituents, the lead/emulsion bricks, the neutrino interactions have occurred and also to give calorimetric information about each event. The technology used consists in walls of two planes of plastic scintillator strips, one per transverse direction. Wavelength shifting fibres collect the light signal emitted by the scintillator strips and guide it to both ends where it is read by multi-anode photomultiplier tubes. All the elements used in the construction of this detector and its main characteristics are described.

  10. Chemical Proteomics Reveals Ferrochelatase as a Common Off-target of Kinase Inhibitors.

    Science.gov (United States)

    Klaeger, Susan; Gohlke, Bjoern; Perrin, Jessica; Gupta, Vipul; Heinzlmeir, Stephanie; Helm, Dominic; Qiao, Huichao; Bergamini, Giovanna; Handa, Hiroshi; Savitski, Mikhail M; Bantscheff, Marcus; Médard, Guillaume; Preissner, Robert; Kuster, Bernhard

    2016-05-20

    Many protein kinases are valid drug targets in oncology because they are key components of signal transduction pathways. The number of clinical kinase inhibitors is on the rise, but these molecules often exhibit polypharmacology, potentially eliciting desired and toxic effects. Therefore, a comprehensive assessment of a compound's target space is desirable for a better understanding of its biological effects. The enzyme ferrochelatase (FECH) catalyzes the conversion of protoporphyrin IX into heme and was recently found to be an off-target of the BRAF inhibitor Vemurafenib, likely explaining the phototoxicity associated with this drug in melanoma patients. This raises the question of whether FECH binding is a more general feature of kinase inhibitors. To address this, we applied a chemical proteomics approach using kinobeads to evaluate 226 clinical kinase inhibitors for their ability to bind FECH. Surprisingly, low or submicromolar FECH binding was detected for 29 of all compounds tested and isothermal dose response measurements confirmed target engagement in cells. We also show that Vemurafenib, Linsitinib, Neratinib, and MK-2461 reduce heme levels in K562 cells, verifying that drug binding leads to a loss of FECH activity. Further biochemical and docking experiments identified the protoporphyrin pocket in FECH as one major drug binding site. Since the genetic loss of FECH activity leads to photosensitivity in humans, our data strongly suggest that FECH inhibition by kinase inhibitors is the molecular mechanism triggering photosensitivity in patients. We therefore suggest that a FECH assay should generally be part of the preclinical molecular toxicology package for the development of kinase inhibitors.

  11. Identification of lactoferricin B intracellular targets using an Escherichia coli proteome chip.

    Science.gov (United States)

    Tu, Yu-Hsuan; Ho, Yu-Hsuan; Chuang, Ying-Chih; Chen, Po-Chung; Chen, Chien-Sheng

    2011-01-01

    Lactoferricin B (LfcinB) is a well-known antimicrobial peptide. Several studies have indicated that it can inhibit bacteria by affecting intracellular activities, but the intracellular targets of this antimicrobial peptide have not been identified. Therefore, we used E. coli proteome chips to identify the intracellular target proteins of LfcinB in a high-throughput manner. We probed LfcinB with E. coli proteome chips and further conducted normalization and Gene Ontology (GO) analyses. The results of the GO analyses showed that the identified proteins were associated with metabolic processes. Moreover, we validated the interactions between LfcinB and chip assay-identified proteins with fluorescence polarization (FP) assays. Sixteen proteins were identified, and an E. coli interaction database (EcID) analysis revealed that the majority of the proteins that interact with these 16 proteins affected the tricarboxylic acid (TCA) cycle. Knockout assays were conducted to further validate the FP assay results. These results showed that phosphoenolpyruvate carboxylase was a target of LfcinB, indicating that one of its mechanisms of action may be associated with pyruvate metabolism. Thus, we used pyruvate assays to conduct an in vivo validation of the relationship between LfcinB and pyruvate level in E. coli. These results showed that E. coli exposed to LfcinB had abnormal pyruvate amounts, indicating that LfcinB caused an accumulation of pyruvate. In conclusion, this study successfully revealed the intracellular targets of LfcinB using an E. coli proteome chip approach.

  12. Targeted Proteomics to Assess the Response to Anti-Angiogenic Treatment in Human Glioblastoma (GBM).

    Science.gov (United States)

    Demeure, Kevin; Fack, Fred; Duriez, Elodie; Tiemann, Katja; Bernard, Amandine; Golebiewska, Anna; Bougnaud, Sébastien; Bjerkvig, Rolf; Domon, Bruno; Niclou, Simone P

    2016-02-01

    Glioblastoma (GBM) is a highly aggressive primary brain tumor with dismal outcome for affected patients. Because of the significant neo-angiogenesis exhibited by GBMs, anti-angiogenic therapies have been intensively evaluated during the past years. Recent clinical studies were however disappointing, although a subpopulation of patients may benefit from such treatment. We have previously shown that anti-angiogenic targeting in GBM increases hypoxia and leads to a metabolic adaptation toward glycolysis, suggesting that combination treatments also targeting the glycolytic phenotype may be effective in GBM patients. The aim of this study was to identify marker proteins that are altered by treatment and may serve as a short term readout of anti-angiogenic therapy. Ultimately such proteins could be tested as markers of efficacy able to identify patient subpopulations responsive to the treatment. We applied a proteomics approach based on selected reaction monitoring (SRM) to precisely quantify targeted protein candidates, selected from pathways related to metabolism, apoptosis and angiogenesis. The workflow was developed in the context of patient-derived intracranial GBM xenografts developed in rodents and ensured the specific identification of human tumor versus rodent stroma-derived proteins. Quality control experiments were applied to assess sample heterogeneity and reproducibility of SRM assays at different levels. The data demonstrate that tumor specific proteins can be precisely quantified within complex biological samples, reliably identifying small concentration differences induced by the treatment. In line with previous work, we identified decreased levels of TCA cycle enzymes, including isocitrate dehydrogenase, whereas malectin, calnexin, and lactate dehydrogenase A were augmented after treatment. We propose the most responsive proteins of our subset as potential novel biomarkers to assess treatment response after anti-angiogenic therapy that warrant future

  13. Automated selected reaction monitoring data analysis workflow for large-scale targeted proteomic studies.

    Science.gov (United States)

    Surinova, Silvia; Hüttenhain, Ruth; Chang, Ching-Yun; Espona, Lucia; Vitek, Olga; Aebersold, Ruedi

    2013-08-01

    Targeted proteomics based on selected reaction monitoring (SRM) mass spectrometry is commonly used for accurate and reproducible quantification of protein analytes in complex biological mixtures. Strictly hypothesis-driven, SRM assays quantify each targeted protein by collecting measurements on its peptide fragment ions, called transitions. To achieve sensitive and accurate quantitative results, experimental design and data analysis must consistently account for the variability of the quantified transitions. This consistency is especially important in large experiments, which increasingly require profiling up to hundreds of proteins over hundreds of samples. Here we describe a robust and automated workflow for the analysis of large quantitative SRM data sets that integrates data processing, statistical protein identification and quantification, and dissemination of the results. The integrated workflow combines three software tools: mProphet for peptide identification via probabilistic scoring; SRMstats for protein significance analysis with linear mixed-effect models; and PASSEL, a public repository for storage, retrieval and query of SRM data. The input requirements for the protocol are files with SRM traces in mzXML format, and a file with a list of transitions in a text tab-separated format. The protocol is especially suited for data with heavy isotope-labeled peptide internal standards. We demonstrate the protocol on a clinical data set in which the abundances of 35 biomarker candidates were profiled in 83 blood plasma samples of subjects with ovarian cancer or benign ovarian tumors. The time frame to realize the protocol is 1-2 weeks, depending on the number of replicates used in the experiment.

  14. Development and application of a quantitative multiplexed small GTPase activity assay using targeted proteomics.

    Science.gov (United States)

    Zhang, Cheng-Cheng; Li, Ru; Jiang, Honghui; Lin, Shujun; Rogalski, Jason C; Liu, Kate; Kast, Juergen

    2015-02-06

    Small GTPases are a family of key signaling molecules that are ubiquitously expressed in various types of cells. Their activity is often analyzed by western blot, which is limited by its multiplexing capability, the quality of isoform-specific antibodies, and the accuracy of quantification. To overcome these issues, a quantitative multiplexed small GTPase activity assay has been developed. Using four different binding domains, this assay allows the binding of up to 12 active small GTPase isoforms simultaneously in a single experiment. To accurately quantify the closely related small GTPase isoforms, a targeted proteomic approach, i.e., selected/multiple reaction monitoring, was developed, and its functionality and reproducibility were validated. This assay was successfully applied to human platelets and revealed time-resolved coactivation of multiple small GTPase isoforms in response to agonists and differential activation of these isoforms in response to inhibitor treatment. This widely applicable approach can be used for signaling pathway studies and inhibitor screening in many cellular systems.

  15. Proteomics analysis of antimalarial targets of Garcinia mangostana Linn.

    Institute of Scientific and Technical Information of China (English)

    Wanna; Chaijaroenkul; Artitiya; Thiengsusuk; Kanchana; Rungsihirunrat; Stephen; Andrew; Ward; Kesara; Na-Bangchang

    2014-01-01

    Objective:To investigate possible protein targets for antimalarial activity of Garcina mangostana Linn.(G.mangostana)(pericarp)in 3D7 Plasmodium falciparum clone using 2-dimensional electrophoresis and liquid chromatography mass-spectrometry(LC/MS/MS).Methods:3D7 Plasmodium falciparum was exposed to the crude ethanolic extract of G.mangostana Linn.(pericarp)at the concentrations of 12μg/mL(1C50level:concentration that inhibits parasite growth by 50%)and 30μg/mL(1C90level:concentration that inhibits parasite growth by 90%)for 12 h.Parasite proteins were separated by 2-dimensional electrophoresis and identified by LC/MS/MS.Results:At the IC50concentration,about 82%of the expressed parasite proteins were matched with the control(non-exposed),while at the IC90concentration,only 15%matched proteins were found.The selected protein spots from parasite exposed to the plant extract at the concentration of 12μg/mL were identified as eneymes that play role in glycolysis pathway,i.e.,phosphoglyeerate mutase putative,L-lactate dehydrogenase/glyceraldehyde-3-phosphate dehydrogenase,and fruetose-bisphosphate aldolase/phosphoglyeerate kinase.The proteosome was found in parasite exposed to 30μg/mL of the extract.Conclusions:Results suggest that proteins involved in the glycolysis pathway may be the targets for antimalarial activity of G.mangostana Linn.(pericarp).

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

    Science.gov (United States)

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

    2014-01-01

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

  17. A quality control of proteomic experiments based on multiple isotopologous internal standards

    Directory of Open Access Journals (Sweden)

    Adele Bourmaud

    2015-09-01

    Full Text Available The harmonization of proteomics experiments facilitates the exchange and comparison of results. The definition of standards and metrics ensures reliable and consistent data quality. An internal quality control procedure was developed to assess the different steps of a proteomic analysis workflow and perform a system suitability test. The method relies on a straightforward protocol using a simple mixture of exogenous proteins, and the sequential addition of two sets of isotopically labeled peptides added to reference samples. This internal quality control procedure was applied to plasma samples to demonstrate its easy implementation, which makes it generic for most proteomics applications.

  18. Identification of lactoferricin B intracellular targets using an Escherichia coli proteome chip.

    Directory of Open Access Journals (Sweden)

    Yu-Hsuan Tu

    Full Text Available Lactoferricin B (LfcinB is a well-known antimicrobial peptide. Several studies have indicated that it can inhibit bacteria by affecting intracellular activities, but the intracellular targets of this antimicrobial peptide have not been identified. Therefore, we used E. coli proteome chips to identify the intracellular target proteins of LfcinB in a high-throughput manner. We probed LfcinB with E. coli proteome chips and further conducted normalization and Gene Ontology (GO analyses. The results of the GO analyses showed that the identified proteins were associated with metabolic processes. Moreover, we validated the interactions between LfcinB and chip assay-identified proteins with fluorescence polarization (FP assays. Sixteen proteins were identified, and an E. coli interaction database (EcID analysis revealed that the majority of the proteins that interact with these 16 proteins affected the tricarboxylic acid (TCA cycle. Knockout assays were conducted to further validate the FP assay results. These results showed that phosphoenolpyruvate carboxylase was a target of LfcinB, indicating that one of its mechanisms of action may be associated with pyruvate metabolism. Thus, we used pyruvate assays to conduct an in vivo validation of the relationship between LfcinB and pyruvate level in E. coli. These results showed that E. coli exposed to LfcinB had abnormal pyruvate amounts, indicating that LfcinB caused an accumulation of pyruvate. In conclusion, this study successfully revealed the intracellular targets of LfcinB using an E. coli proteome chip approach.

  19. Identification and characterization of angiogenesis targets through proteomic profiling of endothelial cells in human cancer tissues.

    Directory of Open Access Journals (Sweden)

    Mehdi Mesri

    Full Text Available Genomic and proteomic analysis of normal and cancer tissues has yielded abundant molecular information for potential biomarker and therapeutic targets. Considering potential advantages in accessibility to pharmacological intervention, identification of targets resident on the vascular endothelium within tumors is particularly attractive. By employing mass spectrometry (MS as a tool to identify proteins that are over-expressed in tumor-associated endothelium relative to normal cells, we aimed to discover targets that could be utilized in tumor angiogenesis cancer therapy. We developed proteomic methods that allowed us to focus our studies on the discovery of cell surface/secreted proteins, as they represent key antibody therapeutic and biomarker opportunities. First, we isolated endothelial cells (ECs from human normal and kidney cancer tissues by FACS using CD146 as a marker. Additionally, dispersed human colon and lung cancer tissues and their corresponding normal tissues were cultured ex-vivo and their endothelial content were preferentially expanded, isolated and passaged. Cell surface proteins were then preferentially captured, digested with trypsin and subjected to MS-based proteomic analysis. Peptides were first quantified, and then the sequences of differentially expressed peptides were resolved by MS analysis. A total of 127 unique non-overlapped (157 total tumor endothelial cell over-expressed proteins identified from directly isolated kidney-associated ECs and those identified from ex-vivo cultured lung and colon tissues including known EC markers such as CD146, CD31, and VWF. The expression analyses of a panel of the identified targets were confirmed by immunohistochemistry (IHC including CD146, B7H3, Thy-1 and ATP1B3. To determine if the proteins identified mediate any functional role, we performed siRNA studies which led to previously unidentified functional dependency for B7H3 and ATP1B3.

  20. Clinical proteomics

    DEFF Research Database (Denmark)

    Albrethsen, Jakob; Frederiksen, Hanne; Johannsen, Trine Holm

    2018-01-01

    Clinical proteomics aims to deliver cost-effective multiplexing of potentially hundreds of diagnostic proteins, including distinct protein isoforms. The analytical strategy known as targeted proteomics is particularly promising because it is compatible with robust mass spectrometry (MS)-platforms...... standards and calibrants. The present challenge is to examine if targeted proteomics of IGF-I can truly measure up to the routine performance that must be expected from a clinical testing platform.......Clinical proteomics aims to deliver cost-effective multiplexing of potentially hundreds of diagnostic proteins, including distinct protein isoforms. The analytical strategy known as targeted proteomics is particularly promising because it is compatible with robust mass spectrometry (MS......)-platforms already implemented in many clinical laboratories for routine quantitation of small molecules (i.e. uHPLC coupled to triple-quadrupole MS). Progress in targeted proteomics of circulating insulin-like growth factor 1 (IGF-I) have provided valuable insights about tryptic peptides, transitions, internal...

  1. In silico design of targeted SRM-based experiments

    Directory of Open Access Journals (Sweden)

    Nahnsen Sven

    2012-11-01

    Full Text Available Abstract Selected reaction monitoring (SRM-based proteomics approaches enable highly sensitive and reproducible assays for profiling of thousands of peptides in one experiment. The development of such assays involves the determination of retention time, detectability and fragmentation properties of peptides, followed by an optimal selection of transitions. If those properties have to be identified experimentally, the assay development becomes a time-consuming task. We introduce a computational framework for the optimal selection of transitions for a given set of proteins based on their sequence information alone or in conjunction with already existing transition databases. The presented method enables the rapid and fully automated initial development of assays for targeted proteomics. We introduce the relevant methods, report and discuss a step-wise and generic protocol and we also show that we can reach an ad hoc coverage of 80 % of the targeted proteins. The presented algorithmic procedure is implemented in the open-source software package OpenMS/TOPP.

  2. Expression proteomics study to determine metallodrug targets and optimal drug combinations.

    Science.gov (United States)

    Lee, Ronald F S; Chernobrovkin, Alexey; Rutishauser, Dorothea; Allardyce, Claire S; Hacker, David; Johnsson, Kai; Zubarev, Roman A; Dyson, Paul J

    2017-05-08

    The emerging technique termed functional identification of target by expression proteomics (FITExP) has been shown to identify the key protein targets of anti-cancer drugs. Here, we use this approach to elucidate the proteins involved in the mechanism of action of two ruthenium(II)-based anti-cancer compounds, RAPTA-T and RAPTA-EA in breast cancer cells, revealing significant differences in the proteins upregulated. RAPTA-T causes upregulation of multiple proteins suggesting a broad mechanism of action involving suppression of both metastasis and tumorigenicity. RAPTA-EA bearing a GST inhibiting ethacrynic acid moiety, causes upregulation of mainly oxidative stress related proteins. The approach used in this work could be applied to the prediction of effective drug combinations to test in cancer chemotherapy clinical trials.

  3. Partitioning the proteome: phase separation for targeted analysis of membrane proteins in human post-mortem brain.

    Directory of Open Access Journals (Sweden)

    Jane A English

    Full Text Available Neuroproteomics is a powerful platform for targeted and hypothesis driven research, providing comprehensive insights into cellular and sub-cellular disease states, Gene × Environmental effects, and cellular response to medication effects in human, animal, and cell culture models. Analysis of sub-proteomes is becoming increasingly important in clinical proteomics, enriching for otherwise undetectable proteins that are possible markers for disease. Membrane proteins are one such sub-proteome class that merit in-depth targeted analysis, particularly in psychiatric disorders. As membrane proteins are notoriously difficult to analyse using traditional proteomics methods, we evaluate a paradigm to enrich for and study membrane proteins from human post-mortem brain tissue. This is the first study to extensively characterise the integral trans-membrane spanning proteins present in human brain. Using Triton X-114 phase separation and LC-MS/MS analysis, we enriched for and identified 494 membrane proteins, with 194 trans-membrane helices present, ranging from 1 to 21 helices per protein. Isolated proteins included glutamate receptors, G proteins, voltage gated and calcium channels, synaptic proteins, and myelin proteins, all of which warrant quantitative proteomic investigation in psychiatric and neurological disorders. Overall, our sub-proteome analysis reduced sample complexity and enriched for integral membrane proteins by 2.3 fold, thus allowing for more manageable, reproducible, and targeted proteomics in case vs. control biomarker studies. This study provides a valuable reference for future neuroproteomic investigations of membrane proteins, and validates the use Triton X-114 detergent phase extraction on human post mortem brain.

  4. Targets for the APEX experiment at ATLAS

    International Nuclear Information System (INIS)

    Greene, J.P.; Thomas, G.E.; Leonard, R.H.

    1994-01-01

    Targets of lead, tantalum, thorium and uranium have been produced for experiments with the APEX (Argonne Positron Experiment) apparatus at ATLAS (Argonne Tandem Linac Accelerator System). APEX is a device built at Argonne National Laboratory to investigate the anomalous positrons observed in collisions of very heavy ion beams on heavy targets. Both fixed and rotating targets have been used. The rotating target system involves a 4-quadrant wheel rotating at speeds up to 700 rpm with the position encoded into the data stream. In addition to the hundreds of targets produced for the heavy-ion reactions studied, a wide variety of targets were employed for beam diagnostics, detector calibration and target wheel development. The experiment used very heavy ion beams ( 238 U, 206 Pb and 208 Pb) from ATLAS and targets of 206 Pb, 208 Pb, 232 Th and 238 U produced in the laboratory

  5. Technological advances and proteomic applications in drug discovery and target deconvolution: identification of the pleiotropic effects of statins.

    Science.gov (United States)

    Banfi, Cristina; Baetta, Roberta; Gianazza, Erica; Tremoli, Elena

    2017-06-01

    Proteomic-based techniques provide a powerful tool for identifying the full spectrum of protein targets of a drug, elucidating its mechanism(s) of action, and identifying biomarkers of its efficacy and safety. Herein, we outline the technological advancements in the field, and illustrate the contribution of proteomics to the definition of the pharmacological profile of statins, which represent the cornerstone of the prevention and treatment of cardiovascular diseases (CVDs). Statins act by inhibiting 3-hydroxy-3-methyl-glutaryl-coenzyme A (HMG-CoA) reductase, thus reducing cholesterol biosynthesis and consequently enhancing the clearance of low-density lipoproteins from the blood; however, HMG-CoA reductase inhibition can result in a multitude of additional effects beyond lipid lowering, known as 'pleiotropic effects'. The case of statins highlights the unique contribution of proteomics to the target profiling of a drug molecule. Copyright © 2017 Elsevier Ltd. All rights reserved.

  6. Identification of BAG3 target proteins in anaplastic thyroid cancer cells by proteomic analysis.

    Science.gov (United States)

    Galdiero, Francesca; Bello, Anna Maria; Spina, Anna; Capiluongo, Anna; Liuu, Sophie; De Marco, Margot; Rosati, Alessandra; Capunzo, Mario; Napolitano, Maria; Vuttariello, Emilia; Monaco, Mario; Califano, Daniela; Turco, Maria Caterina; Chiappetta, Gennaro; Vinh, Joëlle; Chiappetta, Giovanni

    2018-01-30

    BAG3 protein is an apoptosis inhibitor and is highly expressed in Anaplastic Thyroid Cancer. We investigated the entire set of proteins modulated by BAG3 silencing in the human anaplastic thyroid 8505C cancer cells by using the Stable-Isotope Labeling by Amino acids in Cell culture strategy combined with mass spectrometry analysis. By this approach we identified 37 up-regulated and 54 down-regulated proteins in BAG3-silenced cells. Many of these proteins are reportedly involved in tumor progression, invasiveness and resistance to therapies. We focused our attention on an oncogenic protein, CAV1, and a tumor suppressor protein, SERPINB2, that had not previously been reported to be modulated by BAG3. Their expression levels in BAG3-silenced cells were confirmed by qRT-PCR and western blot analyses, disclosing two novel targets of BAG3 pro-tumor activity. We also examined the dataset of proteins obtained by the quantitative proteomics analysis using two tools, Downstream Effect Analysis and Upstream Regulator Analysis of the Ingenuity Pathways Analysis software. Our analyses confirm the association of the proteome profile observed in BAG3-silenced cells with an increase in cell survival and a decrease in cell proliferation and invasion, and highlight the possible involvement of four tumor suppressor miRNAs and TP53/63 proteins in BAG3 activity.

  7. Chemical proteomics for target discovery of head-to-tail cyclized mini-proteins

    Science.gov (United States)

    Hellinger, Roland; Thell, Kathrin; Vasileva, Mina; Muhammad, Taj; Gunasekera, Sunithi; Kümmel, Daniel; Göransson, Ulf; Becker, Christian W.; Gruber, Christian W.

    2017-10-01

    Target deconvolution is one of the most challenging tasks in drug discovery, but a key step in drug development. In contrast to small molecules, there is a lack of validated and robust methodologies for target elucidation of peptides. In particular, it is difficult to apply these methods to cyclic and cysteine-stabilized peptides since they exhibit reduced amenability to chemical modification and affinity capture; however, such ribosomal synthesized and post-translationally modified peptide natural products are rich sources of promising drug candidates. For example, plant-derived circular peptides called cyclotides have recently attracted much attention due to their immunosuppressive effects and oral activity in the treatment of multiple sclerosis in mice, but their molecular target has hitherto not been reported. In this study a chemical proteomics approach using photo-affinity crosslinking was developed to determine a target of the circular peptide [T20K]kalata B1. Using this prototypic nature-derived peptide enabled the identification of a possible modulation of 14-3-3 proteins. This biochemical interaction was validated via competition pull down assays as well as a cellular reporter assay indicating an effect on 14-3-3-dependent transcriptional activity. As proof of concept, the presented approach may be applicable for target elucidation of various cyclic peptides and mini-proteins, in particular cyclotides, which represent a promising class of molecules in drug discovery and development.

  8. Mapping in vivo target interaction profiles of covalent inhibitors using chemical proteomics with label-free quantification.

    Science.gov (United States)

    van Rooden, Eva J; Florea, Bogdan I; Deng, Hui; Baggelaar, Marc P; van Esbroeck, Annelot C M; Zhou, Juan; Overkleeft, Herman S; van der Stelt, Mario

    2018-04-01

    Activity-based protein profiling (ABPP) has emerged as a valuable chemical proteomics method to guide the therapeutic development of covalent drugs by assessing their on-target engagement and off-target activity. We recently used ABPP to determine the serine hydrolase interaction landscape of the experimental drug BIA 10-2474, thereby providing a potential explanation for the adverse side effects observed with this compound. ABPP allows mapping of protein interaction landscapes of inhibitors in cells, tissues and animal models. Whereas our previous protocol described quantification of proteasome activity using stable-isotope labeling, this protocol describes the procedures for identifying the in vivo selectivity profile of covalent inhibitors with label-free quantitative proteomics. The optimization of our protocol for label-free quantification methods results in high proteome coverage and allows the comparison of multiple biological samples. We demonstrate our protocol by assessing the protein interaction landscape of the diacylglycerol lipase inhibitor DH376 in mouse brain, liver, kidney and testes. The stages of the protocol include tissue lysis, probe incubation, target enrichment, sample preparation, liquid chromatography-mass spectrometry (LC-MS) measurement, data processing and analysis. This approach can be used to study target engagement in a native proteome and to identify potential off targets for the inhibitor under investigation. The entire protocol takes at least 4 d, depending on the number of samples.

  9. AGS Spallation Target Experiment (ASTE) Collaboration

    International Nuclear Information System (INIS)

    Oyama, Yukio

    1999-01-01

    An experiment on mercury spallation target with high energy proton beam, called as the AGS Spallation Target Experiment (ASTE) Collaboration, has been performed at Alternating Gradient Synchrotron (AGS) of Brookhaven National Laboratory (BNL) in USA, in cooperation among the laboratories in Japan, Europe and USA. The experimental setup, scope and preliminary results are presented in the paper. (author)

  10. Specter: linear deconvolution for targeted analysis of data-independent acquisition mass spectrometry proteomics.

    Science.gov (United States)

    Peckner, Ryan; Myers, Samuel A; Jacome, Alvaro Sebastian Vaca; Egertson, Jarrett D; Abelin, Jennifer G; MacCoss, Michael J; Carr, Steven A; Jaffe, Jacob D

    2018-05-01

    Mass spectrometry with data-independent acquisition (DIA) is a promising method to improve the comprehensiveness and reproducibility of targeted and discovery proteomics, in theory by systematically measuring all peptide precursors in a biological sample. However, the analytical challenges involved in discriminating between peptides with similar sequences in convoluted spectra have limited its applicability in important cases, such as the detection of single-nucleotide polymorphisms (SNPs) and alternative site localizations in phosphoproteomics data. We report Specter (https://github.com/rpeckner-broad/Specter), an open-source software tool that uses linear algebra to deconvolute DIA mixture spectra directly through comparison to a spectral library, thus circumventing the problems associated with typical fragment-correlation-based approaches. We validate the sensitivity of Specter and its performance relative to that of other methods, and show that Specter is able to successfully analyze cases involving highly similar peptides that are typically challenging for DIA analysis methods.

  11. A qualitative and quantitative evaluation of the peptide characteristics of microwave- and ultrasound-assisted digestion in discovery and targeted proteomic analyses.

    Science.gov (United States)

    Guo, Zhengguang; Cheng, Jie; Sun, Haidan; Sun, Wei

    2017-08-30

    Fast digestion methods can dramatically accelerate enzyme digestion and increase the throughput of proteomic analysis. However, the peptide characteristics of fast digestion methods and their performance in discovery and targeted proteomic analysis must be systematically evaluated. Three digestion methods, including overnight digestion, microwave-assisted protein enzymatic digestion (MAPED), and high-intensity focused ultrasonic-assisted enzymatic digestion (HIFUSAED), in trypsin or in trypsin/Lys-C were comprehensively compared in both discovery and targeted proteomics analysis using the HeLa cell proteome. In discovery proteomic analysis, the highest numbers of peptides and proteins were identified when the sample was digested via the MAPED method with trypsin/Lys-C. The fast digestion methods showed a higher mis-cleavage rate and a lower semi-tryptic rate than the overnight digestion method. In both label-free quantitative analysis and targeted proteomic analysis, both fully cleaved peptides (FCPs) and mis-cleaved peptides (MCPs) from the fast digestion methods and the overnight digestion method showed good reproducibility if they showed good abundance. When both the FCPs and MCPs were included in the analysis, the MAPED with trypsin/Lys-C method showed the best results for both discovery proteomic analysis and relative quantitative targeted proteomic analysis. These results will be beneficial for the application of fast digestion methods to proteomics. Copyright © 2017 John Wiley & Sons, Ltd.

  12. Genomes2Drugs: identifies target proteins and lead drugs from proteome data.

    LENUS (Irish Health Repository)

    Toomey, David

    2009-01-01

    BACKGROUND: Genome sequencing and bioinformatics have provided the full hypothetical proteome of many pathogenic organisms. Advances in microarray and mass spectrometry have also yielded large output datasets of possible target proteins\\/genes. However, the challenge remains to identify new targets for drug discovery from this wealth of information. Further analysis includes bioinformatics and\\/or molecular biology tools to validate the findings. This is time consuming and expensive, and could fail to yield novel drugs if protein purification and crystallography is impossible. To pre-empt this, a researcher may want to rapidly filter the output datasets for proteins that show good homology to proteins that have already been structurally characterised or proteins that are already targets for known drugs. Critically, those researchers developing novel antibiotics need to select out the proteins that show close homology to any human proteins, as future inhibitors are likely to cross-react with the host protein, causing off-target toxicity effects later in clinical trials. METHODOLOGY\\/PRINCIPAL FINDINGS: To solve many of these issues, we have developed a free online resource called Genomes2Drugs which ranks sequences to identify proteins that are (i) homologous to previously crystallized proteins or (ii) targets of known drugs, but are (iii) not homologous to human proteins. When tested using the Plasmodium falciparum malarial genome the program correctly enriched the ranked list of proteins with known drug target proteins. CONCLUSIONS\\/SIGNIFICANCE: Genomes2Drugs rapidly identifies proteins that are likely to succeed in drug discovery pipelines. This free online resource helps in the identification of potential drug targets. Importantly, the program further highlights proteins that are likely to be inhibited by FDA-approved drugs. These drugs can then be rapidly moved into Phase IV clinical studies under \\'change-of-application\\' patents.

  13. Genomes2Drugs: identifies target proteins and lead drugs from proteome data.

    Directory of Open Access Journals (Sweden)

    David Toomey

    Full Text Available BACKGROUND: Genome sequencing and bioinformatics have provided the full hypothetical proteome of many pathogenic organisms. Advances in microarray and mass spectrometry have also yielded large output datasets of possible target proteins/genes. However, the challenge remains to identify new targets for drug discovery from this wealth of information. Further analysis includes bioinformatics and/or molecular biology tools to validate the findings. This is time consuming and expensive, and could fail to yield novel drugs if protein purification and crystallography is impossible. To pre-empt this, a researcher may want to rapidly filter the output datasets for proteins that show good homology to proteins that have already been structurally characterised or proteins that are already targets for known drugs. Critically, those researchers developing novel antibiotics need to select out the proteins that show close homology to any human proteins, as future inhibitors are likely to cross-react with the host protein, causing off-target toxicity effects later in clinical trials. METHODOLOGY/PRINCIPAL FINDINGS: To solve many of these issues, we have developed a free online resource called Genomes2Drugs which ranks sequences to identify proteins that are (i homologous to previously crystallized proteins or (ii targets of known drugs, but are (iii not homologous to human proteins. When tested using the Plasmodium falciparum malarial genome the program correctly enriched the ranked list of proteins with known drug target proteins. CONCLUSIONS/SIGNIFICANCE: Genomes2Drugs rapidly identifies proteins that are likely to succeed in drug discovery pipelines. This free online resource helps in the identification of potential drug targets. Importantly, the program further highlights proteins that are likely to be inhibited by FDA-approved drugs. These drugs can then be rapidly moved into Phase IV clinical studies under 'change-of-application' patents.

  14. Identification of Thioredoxin Disulfide Targets Using a Quantitative Proteomics Approach Based on Isotope-Coded Affinity Tags

    DEFF Research Database (Denmark)

    Hägglund, Per; Bunkenborg, Jakob; Maeda, Kenji

    2008-01-01

    Thioredoxin (Trx) is a ubiquitous protein disulfide reductase involved in a wide range of cellular redox processes. A large number of putative target proteins have been identified using proteomics approaches, but insight into target specificity at the molecular level is lacking since the reactivity...... of Trx toward individual disulfides has not been quantified. Here, a novel proteomics procedure is described for quantification of Trx-mediated target disulfide reduction based on thiol-specific differential labeling with the iodoacetamide-based isotope-coded affinity tag (ICAT) reagents. Briefly......, protein extract of embryos from germinated barley seeds was treated +/- Trx, and thiols released from target protein disulfides were irreversibly blocked with iodoacetamide. The remaining cysteine residues in the Trx-treated and the control (-Trx) samples were then chemically reduced and labeled...

  15. Determination of variation parameters as a crucial step in designing TMT-based clinical proteomics experiments.

    Directory of Open Access Journals (Sweden)

    Evelyne Maes

    Full Text Available In quantitative shotgun proteomic analyses by liquid chromatography and mass spectrometry, a rigid study design is necessary in order to obtain statistically relevant results. Hypothesis testing, sample size calculation and power estimation are fundamental concepts that require consideration upon designing an experiment. For this reason, the reproducibility and variability of the proteomic platform needs to be assessed. In this study, we evaluate the technical (sample preparation, labeling (isobaric labels, and total (biological + technical + labeling + experimental variability and reproducibility of a workflow that employs a shotgun LC-MS/MS approach in combination with TMT peptide labeling for the quantification of peripheral blood mononuclear cell (PBMC proteome. We illustrate that the variability induced by TMT labeling is small when compared to the technical variation. The latter is also responsible for a substantial part of the total variation. Prior knowledge about the experimental variability allows for a correct design, a prerequisite for the detection of biologically significant disease-specific differential proteins in clinical proteomics experiments.

  16. Quantitative Proteomics Analysis Identifies Mitochondria as Therapeutic Targets of Multidrug-Resistance in Ovarian Cancer

    Science.gov (United States)

    Chen, Xiulan; Wei, Shasha; Ma, Ying; Lu, Jie; Niu, Gang; Xue, Yanhong; Chen, Xiaoyuan; Yang, Fuquan

    2014-01-01

    Doxorubicin is a widely used chemotherapeutic agent for the treatment of a variety of solid tumors. However, resistance to this anticancer drug is a major obstacle to the effective treatment of tumors. As mitochondria play important roles in cell life and death, we anticipate that mitochondria may be related to drug resistance. Here, stable isotope labeling by amino acids in cell culture (SILAC)-based quantitative proteomic strategy was applied to compare mitochondrial protein expression in doxorubicin sensitive OVCAR8 cells and its doxorubicin-resistant variant NCI_ADR/RES cells. A total of 2085 proteins were quantified, of which 122 proteins displayed significant changes in the NCI_ADR/RES cells. These proteins participated in a variety of cell processes including cell apoptosis, substance metabolism, transport, detoxification and drug metabolism. Then qRT-PCR and western blot were applied to validate the differentially expressed proteins quantified by SILAC. Further functional studies with RNAi demonstrated TOP1MT, a mitochondrial protein participated in DNA repair, was involved in doxorubicin resistance in NCI_ADR/RES cells. Besides the proteomic study, electron microscopy and fluorescence analysis also observed that mitochondrial morphology and localization were greatly altered in NCI_ADR/RES cells. Mitochondrial membrane potential was also decreased in NCI_ADR/RES cells. All these results indicate that mitochondrial function is impaired in doxorubicin-resistant cells and mitochondria play an important role in doxorubicin resistance. This research provides some new information about doxorubicin resistance, indicating that mitochondria could be therapeutic targets of doxorubicin resistance in ovarian cancer cells. PMID:25285166

  17. Normalization for triple-target microarray experiments

    Directory of Open Access Journals (Sweden)

    Magniette Frederic

    2008-04-01

    Full Text Available Abstract Background Most microarray studies are made using labelling with one or two dyes which allows the hybridization of one or two samples on the same slide. In such experiments, the most frequently used dyes are Cy3 and Cy5. Recent improvements in the technology (dye-labelling, scanner and, image analysis allow hybridization up to four samples simultaneously. The two additional dyes are Alexa488 and Alexa494. The triple-target or four-target technology is very promising, since it allows more flexibility in the design of experiments, an increase in the statistical power when comparing gene expressions induced by different conditions and a scaled down number of slides. However, there have been few methods proposed for statistical analysis of such data. Moreover the lowess correction of the global dye effect is available for only two-color experiments, and even if its application can be derived, it does not allow simultaneous correction of the raw data. Results We propose a two-step normalization procedure for triple-target experiments. First the dye bleeding is evaluated and corrected if necessary. Then the signal in each channel is normalized using a generalized lowess procedure to correct a global dye bias. The normalization procedure is validated using triple-self experiments and by comparing the results of triple-target and two-color experiments. Although the focus is on triple-target microarrays, the proposed method can be used to normalize p differently labelled targets co-hybridized on a same array, for any value of p greater than 2. Conclusion The proposed normalization procedure is effective: the technical biases are reduced, the number of false positives is under control in the analysis of differentially expressed genes, and the triple-target experiments are more powerful than the corresponding two-color experiments. There is room for improving the microarray experiments by simultaneously hybridizing more than two samples.

  18. Plasma membrane proteomics of human breast cancer cell lines identifies potential targets for breast cancer diagnosis and treatment.

    Directory of Open Access Journals (Sweden)

    Yvonne S Ziegler

    Full Text Available The use of broad spectrum chemotherapeutic agents to treat breast cancer results in substantial and debilitating side effects, necessitating the development of targeted therapies to limit tumor proliferation and prevent metastasis. In recent years, the list of approved targeted therapies has expanded, and it includes both monoclonal antibodies and small molecule inhibitors that interfere with key proteins involved in the uncontrolled growth and migration of cancer cells. The targeting of plasma membrane proteins has been most successful to date, and this is reflected in the large representation of these proteins as targets of newer therapies. In view of these facts, experiments were designed to investigate the plasma membrane proteome of a variety of human breast cancer cell lines representing hormone-responsive, ErbB2 over-expressing and triple negative cell types, as well as a benign control. Plasma membranes were isolated by using an aqueous two-phase system, and the resulting proteins were subjected to mass spectrometry analysis. Overall, each of the cell lines expressed some unique proteins, and a number of proteins were expressed in multiple cell lines, but in patterns that did not always follow traditional clinical definitions of breast cancer type. From our data, it can be deduced that most cancer cells possess multiple strategies to promote uncontrolled growth, reflected in aberrant expression of tyrosine kinases, cellular adhesion molecules, and structural proteins. Our data set provides a very rich and complex picture of plasma membrane proteins present on breast cancer cells, and the sorting and categorizing of this data provides interesting insights into the biology, classification, and potential treatment of this prevalent and debilitating disease.

  19. Conserved peptide fragmentation as a benchmarking tool for mass spectrometers and a discriminating feature for targeted proteomics.

    Science.gov (United States)

    Toprak, Umut H; Gillet, Ludovic C; Maiolica, Alessio; Navarro, Pedro; Leitner, Alexander; Aebersold, Ruedi

    2014-08-01

    Quantifying the similarity of spectra is an important task in various areas of spectroscopy, for example, to identify a compound by comparing sample spectra to those of reference standards. In mass spectrometry based discovery proteomics, spectral comparisons are used to infer the amino acid sequence of peptides. In targeted proteomics by selected reaction monitoring (SRM) or SWATH MS, predetermined sets of fragment ion signals integrated over chromatographic time are used to identify target peptides in complex samples. In both cases, confidence in peptide identification is directly related to the quality of spectral matches. In this study, we used sets of simulated spectra of well-controlled dissimilarity to benchmark different spectral comparison measures and to develop a robust scoring scheme that quantifies the similarity of fragment ion spectra. We applied the normalized spectral contrast angle score to quantify the similarity of spectra to objectively assess fragment ion variability of tandem mass spectrometric datasets, to evaluate portability of peptide fragment ion spectra for targeted mass spectrometry across different types of mass spectrometers and to discriminate target assays from decoys in targeted proteomics. Altogether, this study validates the use of the normalized spectral contrast angle as a sensitive spectral similarity measure for targeted proteomics, and more generally provides a methodology to assess the performance of spectral comparisons and to support the rational selection of the most appropriate similarity measure. The algorithms used in this study are made publicly available as an open source toolset with a graphical user interface. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

  20. Analysis of biostimulated microbial communities from two field experiments reveals temporal and spatial differences in proteome profiles

    Energy Technology Data Exchange (ETDEWEB)

    Callister, S.J.; Wilkins, M.J.; Nicora, C.D.; Williams, K.H.; Banfield, J.F.; VerBerkmoes, N.C.; Hettich, R.L.; NGuessan, A.L.; Mouser, P.J.; Elifantz, H.; Smith, R.D.; Lovley, D.R.; Lipton, M.S.; Long, P.E.

    2010-07-15

    Stimulated by an acetate-amendment field experiment conducted in 2007, anaerobic microbial populations in the aquifer at the Rifle Integrated Field Research Challenge site in Colorado reduced mobile U(VI) to insoluble U(IV). During this experiment, planktonic biomass was sampled at various time points to quantitatively evaluate proteomes. In 2008, an acetate-amended field experiment was again conducted in a similar manner to the 2007 experiment. As there was no comprehensive metagenome sequence available for use in proteomics analysis, we systematically evaluated 12 different organism genome sequences to generate sets of aggregate genomes, or “pseudo-metagenomes”, for supplying relative quantitative peptide and protein identifications. Proteomics results support previous observations of the dominance of Geobacteraceae during biostimulation using acetate as sole electron donor, and revealed a shift from an early stage of iron reduction to a late stage of iron reduction. Additionally, a shift from iron reduction to sulfate reduction was indicated by changes in the contribution of proteome information contributed by different organism genome sequences within the aggregate set. In addition, the comparison of proteome measurements made between the 2007 field experiment and 2008 field experiment revealed differences in proteome profiles. These differences may be the result of alterations in abundance and population structure within the planktonic biomass samples collected for analysis.

  1. Polarized internal targets for electronuclear experiments

    International Nuclear Information System (INIS)

    van den Brand, J.F.J.

    1993-01-01

    Polarized internal gas targets represent a unique opportunity for the measurement of spin observables in electro-nuclear physics. Two measurements will be discussed. First, spin observables have been measured in elastic and quasi-free scattering of 45, 200, 300, and 415 MeV polarized protons from a polarized 3 He internal gas target at the Indiana University Cyclotron Facility Cooler Ring. The data obtained constitute the first measurement of spin correlation parameters using a storage ring with polarized beam and polarized internal gas target. Second, a quasi-free (e,e'p) experiment using tensor polarized deuterium will be discussed. Here, the goal is the measurement of the S- and D-state parts of the proton spectral function by scattering 700 MeV electrons from an atomic beam source. Large acceptance detectors have been used in both experiments. The internal-target technique has broad applicability in nuclear and particle physics

  2. A high-power target experiment

    CERN Document Server

    Kirk, H G; Ludewig, H; Palmer, Robert; Samulyak, V; Simos, N; Tsang, Thomas; Bradshaw, T W; Drumm, Paul V; Edgecock, T R; Ivanyushenkov, Yury; Bennett, Roger; Efthymiopoulos, Ilias; Fabich, Adrian; Haseroth, H; Haug, F; Lettry, Jacques; Hayato, Y; Yoshimura, Koji; Gabriel, Tony A; Graves, Van; Spampinato, P; Haines, John; McDonald, Kirk T

    2005-01-01

    We describe an experiment designed as a proof-of-principle test for a target system capable of converting a 4 MW proton beam into a high-intensity muon beam suitable for incorporation into either a neutrino factory complex or a muon collider. The target system is based on exposing a free mercury jet to an intense proton beam in the presence of a high strength solenoidal field.

  3. Quantitative proteomics identify molecular targets that are crucial in larval settlement and metamorphosis of bugula neritina

    KAUST Repository

    Zhang, Huoming

    2011-01-07

    The marine invertebrate Bugula neritina has a biphasic life cycle that consists of a swimming larval stage and a sessile juvenile and adult stage. The attachment of larvae to the substratum and their subsequent metamorphosis have crucial ecological consequences. Despite many studies on this species, little is known about the molecular mechanism of these processes. Here, we report a comparative study of swimming larvae and metamorphosing individuals at 4 and 24 h postattachment using label-free quantitative proteomics. We identified more than 1100 proteins at each stage, 61 of which were differentially expressed. Specifically, proteins involved in energy metabolism and structural molecules were generally down-regulated, whereas proteins involved in transcription and translation, the extracellular matrix, and calcification were strongly up-regulated during metamorphosis. Many tightly regulated novel proteins were also identified. Subsequent analysis of the temporal and spatial expressions of some of the proteins and an assay of their functions indicated that they may have key roles in metamorphosis of B. neritina. These findings not only provide molecular evidence with which to elucidate the substantial changes in morphology and physiology that occur during larval attachment and metamorphosis but also identify potential targets for antifouling treatment. © 2011 American Chemical Society.

  4. Thermal experiments in the ADS target model

    International Nuclear Information System (INIS)

    Efanov, A.D.; Orlov, Yu.I.; Sorokin, A.P.; Ivanov, E.F.; Bogoslovskaya, G.P.; Li, N.

    2002-01-01

    Experiments on the development of the target heat model project and method of investigation into heat exchange in target were conducted with the aim of analysis of thermomechanical and strength characteristics of device; experimental data on the temperature distribution in coolant and membrane were obtained. Obtained data demonstrate that the temperature heterogeneity of membrane and coolant are connected with the temperature distribution variability near the membrane. Peculiarities of the experiment are noted: maximal temperature of oscillations at high point of the membrane, and power bearing temperature oscillations in the range 0 - 1 Hz [ru

  5. Statistical methods for quantitative mass spectrometry proteomic experiments with labeling

    Directory of Open Access Journals (Sweden)

    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.

  6. Statistical methods for quantitative mass spectrometry proteomic experiments with labeling.

    Science.gov (United States)

    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.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2017-08-15

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

  8. Babelomics: advanced functional profiling of transcriptomics, proteomics and genomics experiments

    Science.gov (United States)

    Al-Shahrour, Fátima; Carbonell, José; Minguez, Pablo; Goetz, Stefan; Conesa, Ana; Tárraga, Joaquín; Medina, Ignacio; Alloza, Eva; Montaner, David; Dopazo, Joaquín

    2008-01-01

    We present a new version of Babelomics, a complete suite of web tools for the functional profiling of genome scale experiments, with new and improved methods as well as more types of functional definitions. Babelomics includes different flavours of conventional functional enrichment methods as well as more advanced gene set analysis methods that makes it a unique tool among the similar resources available. In addition to the well-known functional definitions (GO, KEGG), Babelomics includes new ones such as Biocarta pathways or text mining-derived functional terms. Regulatory modules implemented include transcriptional control (Transfac, CisRed) and other levels of regulation such as miRNA-mediated interference. Moreover, Babelomics allows for sub-selection of terms in order to test more focused hypothesis. Also gene annotation correspondence tables can be imported, which allows testing with user-defined functional modules. Finally, a tool for the ‘de novo’ functional annotation of sequences has been included in the system. This allows using yet unannotated organisms in the program. Babelomics has been extensively re-engineered and now it includes the use of web services and Web 2.0 technology features, a new user interface with persistent sessions and a new extended database of gene identifiers. Babelomics is available at http://www.babelomics.org PMID:18515841

  9. Plasticity in the proteome of Emiliania huxleyi CCMP 1516 to extremes of light is highly targeted.

    Science.gov (United States)

    McKew, Boyd A; Lefebvre, Stephane C; Achterberg, Eric P; Metodieva, Gergana; Raines, Christine A; Metodiev, Metodi V; Geider, Richard J

    2013-10-01

    Optimality principles are often applied in theoretical studies of microalgal ecophysiology to predict changes in allocation of resources to different metabolic pathways, and optimal acclimation is likely to involve changes in the proteome, which typically accounts for > 50% of cellular nitrogen (N). We tested the hypothesis that acclimation of the microalga Emiliania huxleyi CCMP 1516 to suboptimal vs supraoptimal light involves large changes in the proteome as cells rebalance the capacities to absorb light, fix CO2 , perform biosynthesis and resist photooxidative stress. Emiliania huxleyi was grown in nutrient-replete continuous culture at 30 (LL) and 1000 μmol photons m(-2) s(-1) (HL), and changes in the proteome were assessed by LC-MS/MS shotgun proteomics. Changes were most evident in proteins involved in the light reactions of photosynthesis; the relative abundance of photosystem I (PSI) and PSII proteins was 70% greater in LL, light-harvesting fucoxanthin-chlorophyll proteins (Lhcfs) were up to 500% greater in LL and photoprotective LI818 proteins were 300% greater in HL. The marked changes in the abundances of Lhcfs and LI818s, together with the limited plasticity in the bulk of the E. huxleyi proteome, probably reflect evolutionary pressures to provide energy to maintain metabolic capabilities in stochastic light environments encountered by this species in nature. © 2013 The Authors. New Phytologist © 2013 New Phytologist Trust.

  10. Proton targets for the PHOENICS experiment

    International Nuclear Information System (INIS)

    Kraemer, D.

    1988-10-01

    In the first part of the thesis the construction and test operation of a hydrogen target for the PHOENICS experiment at the Bonn 3.5 GeV accelerator ELSA is described. First of all it shall serve as target for calibration measurements of the counter arrangement. The cooling time of the hydrogen liquefier until the complete filling of the target cell was determined to 4 h 30 m. Via a magnet valve the clearance of the cell into a storage container is possible. In the second part of the thesis measurements on the polarization properties of the target material ammonia are presented. The maximal nucleon polarization in the dilution operation of the cryostat at about 250 mK was determined to 77 -3 +2 % for positive and to 72 -3 +2 % for negative polarization direction and is by this comparable with the values reached for butanol. The required build-up time is with 2.1 h by a factor about two larger than for butanol targets. A determination of Landes g factor of the NH 3 radicals present in the target yielded the value of g = 2.0037. By variation of the magnet field a microwave absorption signal could be taken up which can be identified by the ESR line of the ammonia radical. The half width resulted to 60 ± 5 Gauss. Experiments on the magnet-field dependence of the relaxation time at 1 K and 250 mK showed that in the field-range from 0.4 to 2.5 Tesla the relaxation time varied at 1 K from 16 sec to 14 min and at 250 mK from 2.7 h to 40.3 h. A ratio-formation yielded a crude estimation of the relaxation time to be expected at 50 mK and 0.4 T in the order of magnitude of 2 months. (orig./HSI) [de

  11. An Anti-proteome Nanobody Library Approach Yields a Specific Immunoassay for Trypanosoma congolense Diagnosis Targeting Glycosomal Aldolase.

    Directory of Open Access Journals (Sweden)

    Steven Odongo

    2016-02-01

    Full Text Available Infectious diseases pose a severe worldwide threat to human and livestock health. While early diagnosis could enable prompt preventive interventions, the majority of diseases are found in rural settings where basic laboratory facilities are scarce. Under such field conditions, point-of-care immunoassays provide an appropriate solution for rapid and reliable diagnosis. The limiting steps in the development of the assay are the identification of a suitable target antigen and the selection of appropriate high affinity capture and detection antibodies. To meet these challenges, we describe the development of a Nanobody (Nb-based antigen detection assay generated from a Nb library directed against the soluble proteome of an infectious agent. In this study, Trypanosoma congolense was chosen as a model system.An alpaca was vaccinated with whole-parasite soluble proteome to generate a Nb library from which the most potent T. congolense specific Nb sandwich immunoassay (Nb474H-Nb474B was selected. First, the Nb474-homologous sandwich ELISA (Nb474-ELISA was shown to detect experimental infections with high Positive Predictive Value (98%, Sensitivity (87% and Specificity (94%. Second, it was demonstrated under experimental conditions that the assay serves as test-of-cure after Berenil treatment. Finally, this assay allowed target antigen identification. The latter was independently purified through immuno-capturing from (i T. congolense soluble proteome, (ii T. congolense secretome preparation and (iii sera of T. congolense infected mice. Subsequent mass spectrometry analysis identified the target as T. congolense glycosomal aldolase.The results show that glycosomal aldolase is a candidate biomarker for active T. congolense infections. In addition, and by proof-of-principle, the data demonstrate that the Nb strategy devised here offers a unique approach to both diagnostic development and target discovery that could be widely applied to other infectious

  12. Identification of targets of miR-200b by a SILAC-based quantitative proteomic approach

    Directory of Open Access Journals (Sweden)

    Arivusudar Marimuthu

    2014-09-01

    Full Text Available miRNAs regulate gene expression by binding to cognate mRNAs causing mRNA degradation or translational repression. Mass spectrometry-based proteomic analysis is being widely used to identify miRNA targets. The miR-200b miRNA cluster is often overexpressed in multiple cancer types, but the identity of the targets remains elusive. Using SILAC-based analysis, we examined the effects of overexpression of a miR-200b mimic or a control miRNA in fibrosarcoma cells. We identified around 300 potential targets of miR-200b based on a change in the expression of protein levels. We validated a subset of potential targets at the transcript level using quantitative PCR.

  13. Laser capture microdissection in the genomic and proteomic era: targeting the genetic basis of cancer.

    Science.gov (United States)

    Domazet, Barbara; Maclennan, Gregory T; Lopez-Beltran, Antonio; Montironi, Rodolfo; Cheng, Liang

    2008-03-15

    The advent of new technologies has enabled deeper insight into processes at subcellular levels, which will ultimately improve diagnostic procedures and patient outcome. Thanks to cell enrichment methods, it is now possible to study cells in their native environment. This has greatly contributed to a rapid growth in several areas, such as gene expression analysis, proteomics, and metabolonomics. Laser capture microdissection (LCM) as a method of procuring subpopulations of cells under direct visual inspection is playing an important role in these areas. This review provides an overview of existing LCM technology and its downstream applications in genomics, proteomics, diagnostics and therapy.

  14. The beauty of being (label)-free: sample preparation methods for SWATH-MS and next-generation targeted proteomics

    Science.gov (United States)

    Campbell, Kate; Deery, Michael J.; Lilley, Kathryn S.; Ralser, Markus

    2014-01-01

    The combination of qualitative analysis with label-free quantification has greatly facilitated the throughput and flexibility of novel proteomic techniques. However, such methods rely heavily on robust and reproducible sample preparation procedures. Here, we benchmark a selection of in gel, on filter, and in solution digestion workflows for their application in label-free proteomics. Each procedure was associated with differing advantages and disadvantages. The in gel methods interrogated were cost effective, but were limited in throughput and digest efficiency. Filter-aided sample preparations facilitated reasonable processing times and yielded a balanced representation of membrane proteins, but led to a high signal variation in quantification experiments. Two in solution digest protocols, however, gave optimal performance for label-free proteomics. A protocol based on the detergent RapiGest led to the highest number of detected proteins at second-best signal stability, while a protocol based on acetonitrile-digestion, RapidACN, scored best in throughput and signal stability but came second in protein identification. In addition, we compared label-free data dependent (DDA) and data independent (SWATH) acquisition on a TripleTOF 5600 instrument. While largely similar in protein detection, SWATH outperformed DDA in quantification, reducing signal variation and markedly increasing the number of precisely quantified peptides. PMID:24741437

  15. A Timely shift from shotgun to targeted proteomics and how it can be groundbreaking for cancer research

    DEFF Research Database (Denmark)

    Faria, Sara S.; Morris, Carlos F.M.; Silva, Adriano R.

    2017-01-01

    shifting potential of modern targeted proteomics applied to cancer research can be demonstrated by the large number of advancements and increasing examples of new and more useful biomarkers found during the course of this review in different aspects of cancer research. Out of the many studies dedicated...... to cancer biomarker discovery, we were able to devise some clear trends, such as the fact that breast cancer is the most common type of tumor studied and that most of the research for any given type of cancer is focused on the discovery diagnostic biomarkers, with the exception of those that rely on samples...... applicable results have called for the implementation of more direct, hypothesis-based studies such as those made available through targeted approaches, that might be able to streamline biomarker discovery and validation as a means to increase survivability of affected patients. In fact, the paradigm...

  16. Integration analysis of quantitative proteomics and transcriptomics data identifies potential targets of frizzled-8 protein-related antiproliferative factor in vivo.

    Science.gov (United States)

    Yang, Wei; Kim, Yongsoo; Kim, Taek-Kyun; Keay, Susan K; Kim, Kwang Pyo; Steen, Hanno; Freeman, Michael R; Hwang, Daehee; Kim, Jayoung

    2012-12-01

    identify more differentially expressed genes with a lower false discovery rate from a previously published microarray data set, an integrative hypothesis-testing statistical approach was applied. • For validation experiments, expression and phosphorylation levels of select proteins were evaluated by western blotting. • Integration analysis of this transcriptomics data set with our own quantitative proteomics data set identified 10 genes that are potentially regulated by APF in vivo from 4140 differentially expressed genes identified with a false discovery rate of 1%. • Of these, five (i.e. JUP, MAPKSP1, GSPT1, PTGS2/COX-2 and XPOT) were found to be prominent after network modelling of the common genes identified in the proteomics and microarray studies. • This molecular signature reflects the biological processes of cell adhesion, cell proliferation and inflammation, which is consistent with the known physiological effects of APF. • Lastly, we found the mammalian target of rapamycin pathway was down-regulated in response to APF. • This unbiased integration analysis of in vitro quantitative proteomics data with in vivo quantitative transcriptomics data led to the identification of potential downstream mediators of the APF signal transduction pathway. © 2012 THE AUTHORS. BJU INTERNATIONAL © 2012 BJU INTERNATIONAL.

  17. Biomarker Discovery and Mechanistic Studies of Prostate Cancer Using Targeted Proteomic Approaches

    Science.gov (United States)

    2010-07-01

    EMMPRIN is implicated in metastasis via its ability to confer resistance of breast cancer cells to anoikis by inhibiting BIM [21], and its association with...of Bim . J Biol Chem 2006;281:9719–9727. 22. Gupta N, Wollscheid B, Watts JD, Scheer B, Aebersold R, DeFranco AL. Quantitative proteomic analysis of B...disseminated in electronic form, nor  deployed in part or in whole in any  marketing , promotional or educational  contexts without authorization from

  18. Combining phenotypic and proteomic approaches to identify membrane targets in a ‘triple negative’ breast cancer cell type

    Directory of Open Access Journals (Sweden)

    Rust Steven

    2013-02-01

    Full Text Available Abstract Background The continued discovery of therapeutic antibodies, which address unmet medical needs, requires the continued discovery of tractable antibody targets. Multiple protein-level target discovery approaches are available and these can be used in combination to extensively survey relevant cell membranomes. In this study, the MDA-MB-231 cell line was selected for membranome survey as it is a ‘triple negative’ breast cancer cell line, which represents a cancer subtype that is aggressive and has few treatment options. Methods The MDA-MB-231 breast carcinoma cell line was used to explore three membranome target discovery approaches, which were used in parallel to cross-validate the significance of identified antigens. A proteomic approach, which used membrane protein enrichment followed by protein identification by mass spectrometry, was used alongside two phenotypic antibody screening approaches. The first phenotypic screening approach was based on hybridoma technology and the second was based on phage display technology. Antibodies isolated by the phenotypic approaches were tested for cell specificity as well as internalisation and the targets identified were compared to each other as well as those identified by the proteomic approach. An anti-CD73 antibody derived from the phage display-based phenotypic approach was tested for binding to other ‘triple negative’ breast cancer cell lines and tested for tumour growth inhibitory activity in a MDA-MB-231 xenograft model. Results All of the approaches identified multiple cell surface markers, including integrins, CD44, EGFR, CD71, galectin-3, CD73 and BCAM, some of which had been previously confirmed as being tractable to antibody therapy. In total, 40 cell surface markers were identified for further study. In addition to cell surface marker identification, the phenotypic antibody screening approaches provided reagent antibodies for target validation studies. This is illustrated

  19. Quantification of pancreatic cancer proteome and phosphorylome: indicates molecular events likely contributing to cancer and activity of drug targets.

    Directory of Open Access Journals (Sweden)

    David Britton

    Full Text Available LC-MS/MS phospho-proteomics is an essential technology to help unravel the complex molecular events that lead to and propagate cancer. We have developed a global phospho-proteomic workflow to determine activity of signaling pathways and drug targets in pancreatic cancer tissue for clinical application.Peptides resulting from tryptic digestion of proteins extracted from frozen tissue of pancreatic ductal adenocarcinoma and background pancreas (n = 12, were labelled with tandem mass tags (TMT 8-plex, separated by strong cation exchange chromatography, then were analysed by LC-MS/MS directly or first enriched for phosphopeptides using IMAC and TiO2, prior to analysis. In-house, commercial and freeware bioinformatic platforms were used to identify relevant biological events from the complex dataset.Of 2,101 proteins identified, 152 demonstrated significant difference in abundance between tumor and non-tumor tissue. They included proteins that are known to be up-regulated in pancreatic cancer (e.g. Mucin-1, but the majority were new candidate markers such as HIPK1 & MLCK. Of the 6,543 unique phosphopeptides identified (6,284 unique phosphorylation sites, 635 showed significant regulation, particularly those from proteins involved in cell migration (Rho guanine nucleotide exchange factors & MRCKα and formation of focal adhesions. Activator phosphorylation sites on FYN, AKT1, ERK2, HDAC1 and other drug targets were found to be highly modulated (≥2 fold in different cases highlighting their predictive power.Here we provided critical information enabling us to identify the common and unique molecular events likely contributing to cancer in each case. Such information may be used to help predict more bespoke therapy suitable for an individual case.

  20. Quantification of pancreatic cancer proteome and phosphorylome: indicates molecular events likely contributing to cancer and activity of drug targets.

    Science.gov (United States)

    Britton, David; Zen, Yoh; Quaglia, Alberto; Selzer, Stefan; Mitra, Vikram; Löβner, Christopher; Jung, Stephan; Böhm, Gitte; Schmid, Peter; Prefot, Petra; Hoehle, Claudia; Koncarevic, Sasa; Gee, Julia; Nicholson, Robert; Ward, Malcolm; Castellano, Leandro; Stebbing, Justin; Zucht, Hans Dieter; Sarker, Debashis; Heaton, Nigel; Pike, Ian

    2014-01-01

    LC-MS/MS phospho-proteomics is an essential technology to help unravel the complex molecular events that lead to and propagate cancer. We have developed a global phospho-proteomic workflow to determine activity of signaling pathways and drug targets in pancreatic cancer tissue for clinical application. Peptides resulting from tryptic digestion of proteins extracted from frozen tissue of pancreatic ductal adenocarcinoma and background pancreas (n = 12), were labelled with tandem mass tags (TMT 8-plex), separated by strong cation exchange chromatography, then were analysed by LC-MS/MS directly or first enriched for phosphopeptides using IMAC and TiO2, prior to analysis. In-house, commercial and freeware bioinformatic platforms were used to identify relevant biological events from the complex dataset. Of 2,101 proteins identified, 152 demonstrated significant difference in abundance between tumor and non-tumor tissue. They included proteins that are known to be up-regulated in pancreatic cancer (e.g. Mucin-1), but the majority were new candidate markers such as HIPK1 & MLCK. Of the 6,543 unique phosphopeptides identified (6,284 unique phosphorylation sites), 635 showed significant regulation, particularly those from proteins involved in cell migration (Rho guanine nucleotide exchange factors & MRCKα) and formation of focal adhesions. Activator phosphorylation sites on FYN, AKT1, ERK2, HDAC1 and other drug targets were found to be highly modulated (≥2 fold) in different cases highlighting their predictive power. Here we provided critical information enabling us to identify the common and unique molecular events likely contributing to cancer in each case. Such information may be used to help predict more bespoke therapy suitable for an individual case.

  1. Targeting S100P Inhibits Colon Cancer Growth and Metastasis by Lentivirus-Mediated RNA Interference and Proteomic Analysis

    Science.gov (United States)

    Jiang, Lei; Lai, Yiu-Kay; Zhang, Jinfang; Wang, Hua; Lin, Marie CM; He, Ming-liang; Kung, Hsiang-fu

    2011-01-01

    S100P was recently found to be overexpressed in a variety of cancers and is considered a potential target for cancer therapy, but the functional role or mechanism of action of S100P in colon cancer is not fully understood. In the present study, we knocked down the gene expression of S100P in colon cancer cells using lentivirus-mediated RNA interference. This step resulted in significant inhibition of cancer cell growth, migration and invasion in vitro and tumor growth and liver metastasis in vivo. Moreover, S100P downstream target proteins were identified by proteomic analysis in colon cancer DLD-1 cells with deletion of S100P. Knockdown of S100P led to downregulation of thioredoxin 1 and β-tubulin and upregulation of Rho guanosine diphosphate (GDP) dissociation inhibitor α (RhoGDIA), all potential therapeutic targets in cancer. Taken together, these findings suggest that S100P plays an important role in colon tumorigenesis and metastasis, and the comprehensive and comparative analyses of proteins associated with S100P could contribute to understanding the downstream signal cascade of S100P, leading to tumorigenesis and metastasis. PMID:21327297

  2. [ProteoСat: a tool for planning of proteomic experiments].

    Science.gov (United States)

    Skvortsov, V S; Alekseychuk, N N; Khudyakov, D V; Mikurova, A V; Rybina, A V; Novikova, S E; Tikhonova, O V

    2015-01-01

    ProteoCat is a computer program has been designed to help researchers in the planning of large-scale proteomic experiments. The central part of this program is the subprogram of hydrolysis simulation that supports 4 proteases (trypsin, lysine C, endoproteinases AspN and GluC). For the peptides obtained after virtual hydrolysis or loaded from data file a number of properties important in mass-spectrometric experiments can be calculated or predicted. The data can be analyzed or filtered to reduce a set of peptides. The program is using new and improved modification of our methods developed to predict pI and probability of peptide detection; pI can also be predicted for a number of popular pKa's scales, proposed by other investigators. The algorithm for prediction of peptide retention time was realized similar to the algorithm used in the program SSRCalc. ProteoCat can estimate the coverage of amino acid sequences of proteins under defined limitation on peptides detection, as well as the possibility of assembly of peptide fragments with user-defined size of "sticky" ends. The program has a graphical user interface, written on JAVA and available at http://www.ibmc.msk.ru/LPCIT/ProteoCat.

  3. Comparative proteomics of cerebrospinal fluid reveals a predictive model for differential diagnosis of pneumococcal, meningococcal, and enteroviral meningitis, and novel putative therapeutic targets

    Science.gov (United States)

    2015-01-01

    Background Meningitis is the inflammation of the meninges in response to infection or chemical agents. While aseptic meningitis, most frequently caused by enteroviruses, is usually benign with a self-limiting course, bacterial meningitis remains associated with high morbidity and mortality rates, despite advances in antimicrobial therapy and intensive care. Fast and accurate differential diagnosis is crucial for assertive choice of the appropriate therapeutic approach for each form of meningitis. Methods We used 2D-PAGE and mass spectrometry to identify the cerebrospinal fluid proteome specifically related to the host response to pneumococcal, meningococcal, and enteroviral meningitis. The disease-specific proteome signatures were inspected by pathway analysis. Results Unique cerebrospinal fluid proteome signatures were found to the three aetiological forms of meningitis investigated, and a qualitative predictive model with four protein markers was developed for the differential diagnosis of these diseases. Nevertheless, pathway analysis of the disease-specific proteomes unveiled that Kallikrein-kinin system may play a crucial role in the pathophysiological mechanisms leading to brain damage in bacterial meningitis. Proteins taking part in this cellular process are proposed as putative targets to novel adjunctive therapies. Conclusions Comparative proteomics of cerebrospinal fluid disclosed candidate biomarkers, which were combined in a qualitative and sequential predictive model with potential to improve the differential diagnosis of pneumococcal, meningococcal and enteroviral meningitis. Moreover, we present the first evidence of the possible implication of Kallikrein-kinin system in the pathophysiology of bacterial meningitis. PMID:26040285

  4. Modern proteomic methodologies for the characterization of lactosylation protein targets in milk.

    Science.gov (United States)

    Arena, Simona; Renzone, Giovanni; Novi, Gianfranco; Paffetti, Alessandro; Bernardini, Giulia; Santucci, Annalisa; Scaloni, Andrea

    2010-10-01

    Heat treatment of milk induces the Maillard reaction between lactose and proteins; in this context, β-lactoglobulin and α-lactalbumin adducts have been used as markers to monitor milk quality. Since some milk proteins have been reported as essential for the delivery of microelements and, being resistant against proteolysis in the gastrointestinal tract, also contributing to the acquired immune response against pathogens and the stimulation of cellular proliferation, it is crucial to systematically determine the milk subproteome affected by the Maillard reaction for a careful evaluation of aliment functional properties. This is more important when milk is the unique nutritional source, as in infant diet. To this purpose, a combination of proteomic procedures based on analyte capture by combinatorial peptide ligand libraries, selective trapping of lactosylated peptides by m-aminophenylboronic acid-agarose chromatography and collision-induced dissociation and electron transfer dissociation MS was used for systematic identification of the lactosylated proteins in milk samples subjected to different thermal treatments. An exhaustive modification of proteins was observed in milk powdered preparations for infant nutrition. Globally, this approach allowed the identification of 271 non-redundant modification sites in 33 milk proteins, which also included low-abundance components involved in nutrient delivery, defence response against virus/microorganisms and cellular proliferative events. A comparison of the modified peptide identification percentages resulting from electron transfer dissociation or collision-induced dissociation fragmentation spectra confirmed the first activation mode as most advantageous for the analysis of lactosylated proteins. Nutritional, biological and toxicological consequences of these findings are discussed on the basis of the recent literature on this subject, emphasizing their impact on newborn diet.

  5. Hadron and photon experiments at fixed-target accelerators

    International Nuclear Information System (INIS)

    Diddens, A.N.; Diebold, R.; Gaillard, J.M.; Galaktionov, Yu.V.; Gerstein, S.S.; Pilcheer, J.; Sosnowski, R.

    1979-01-01

    Possible hadron and photon experiments at 20 TeV stationary-target proton accelerator have been considered in order to see typical limitations and possibilities of the experiments in this new energy domain

  6. GE781: a Monte Carlo package for fixed target experiments

    Science.gov (United States)

    Davidenko, G.; Funk, M. A.; Kim, V.; Kuropatkin, N.; Kurshetsov, V.; Molchanov, V.; Rud, S.; Stutte, L.; Verebryusov, V.; Zukanovich Funchal, R.

    The Monte Carlo package for the fixed target experiment B781 at Fermilab, a third generation charmed baryon experiment, is described. This package is based on GEANT 3.21, ADAMO database and DAFT input/output routines.

  7. NCI Requests Cancer Targets for Monoclonal Antibody Production and Characterization | Office of Cancer Clinical Proteomics Research

    Science.gov (United States)

    In an effort to provide well-characterized monoclonal antibodies to the scientific community, NCI's Antibody Characterization Program requests cancer-related protein targets for affinity production and distribution. Submissions will be accepted through July 11, 2014.

  8. NCI Requests Targets for Monoclonal Antibody Production and Characterization | Office of Cancer Clinical Proteomics Research

    Science.gov (United States)

    In an effort to provide well-characterized monoclonal antibodies to the scientific community, NCI's Antibody Characterization Program requests cancer-related protein targets for affinity production and distribution. Submissions will be accepted through July 9, 2012.

  9. Experiments with radioactive target samples at FRANZ

    Science.gov (United States)

    Sonnabend, K.; Altstadt, S.; Beinrucker, C.; Berger, M.; Endres, A.; Fiebiger, S.; Gerbig, J.; Glorius, J.; Göbel, K.; Heftrich, T.; Hinrichs, O.; Koloczek, A.; Lazarus, A.; Lederer, C.; Lier, A.; Mei, B.; Meusel, O.; Mevius, E.; Ostermöller, J.; Plag, R.; Pohl, M.; Reifarth, R.; Schmidt, S.; Slavkovská, Z.; Thomas, B.; Thomas, T.; Weigand, M.; Wolf, C.

    2016-01-01

    The FRANZ facility is currently under construction at Goethe Universität Frankfurt a.M., Germany. It is designed to produce the world's highest neutron intensities in the astrophysically relevant energy range between 10 keV and 1 MeV and consists of a high-intensity proton linac providing energies close to the threshold of the 7Li(p,n) reaction at Ep = 1880 keV. The high intensities of both the proton and the neutron beam allow the investigation of reactions of unstable target isotopes since the needed amount of target material is significantly reduced. We will present two examplary reactions relevant for the s process and the nucleosynthesis of p nuclei, respectively.

  10. Proteome-wide analysis of SUMO2 targets in response to pathological DNA replication stress in human cells.

    Science.gov (United States)

    Bursomanno, Sara; Beli, Petra; Khan, Asif M; Minocherhomji, Sheroy; Wagner, Sebastian A; Bekker-Jensen, Simon; Mailand, Niels; Choudhary, Chunaram; Hickson, Ian D; Liu, Ying

    2015-01-01

    SUMOylation is a form of post-translational modification involving covalent attachment of SUMO (Small Ubiquitin-like Modifier) polypeptides to specific lysine residues in the target protein. In human cells, there are four SUMO proteins, SUMO1-4, with SUMO2 and SUMO3 forming a closely related subfamily. SUMO2/3, in contrast to SUMO1, are predominantly involved in the cellular response to certain stresses, including heat shock. Substantial evidence from studies in yeast has shown that SUMOylation plays an important role in the regulation of DNA replication and repair. Here, we report a proteomic analysis of proteins modified by SUMO2 in response to DNA replication stress in S phase in human cells. We have identified a panel of 22 SUMO2 targets with increased SUMOylation during DNA replication stress, many of which play key functions within the DNA replication machinery and/or in the cellular response to DNA damage. Interestingly, POLD3 was found modified most significantly in response to a low dose aphidicolin treatment protocol that promotes common fragile site (CFS) breakage. POLD3 is the human ortholog of POL32 in budding yeast, and has been shown to act during break-induced recombinational repair. We have also shown that deficiency of POLD3 leads to an increase in RPA-bound ssDNA when cells are under replication stress, suggesting that POLD3 plays a role in the cellular response to DNA replication stress. Considering that DNA replication stress is a source of genome instability, and that excessive replication stress is a hallmark of pre-neoplastic and tumor cells, our characterization of SUMO2 targets during a perturbed S-phase should provide a valuable resource for future functional studies in the fields of DNA metabolism and cancer biology. Copyright © 2014 Elsevier B.V. All rights reserved.

  11. Particle production and targeting experience at the Brookhaven AGS

    International Nuclear Information System (INIS)

    Lazarus, D.M.

    1986-01-01

    Experience in production of secondary pions (neutrinos), kaons and antiprotons by 28.5 GeV/c protons incident on various target materials is given. The problems associated with various target materials with respect to target heating, physical degradation and in some cases, disintegration, are discussed. The effect of target length and production angle on secondary beam flux and optical quality will be illustrated by some incomplete but nonetheless informative data

  12. Reagent Target Request for Monoclonal Antibody Production and Characterization | Office of Cancer Clinical Proteomics Research

    Science.gov (United States)

    NCI's Antibody Characterization Program provides reagents and other critical resources to support protein/peptide measurements and analysis. In an effort to produce and distribute well-characterized monoclonal antibodies to the scientific community, the program is seeking cancer related protein targets for antibody production and characterization for distribution to the research community. Submission Period: May 20, 2011 - July 1, 2011.

  13. Proteomic characterization of Aspergillus fumigatus treated with an antifungal coumarin for identification of novel target molecules of key pathways.

    Science.gov (United States)

    Singh, Seema; Gupta, Shilpi; Singh, Bharat; Sharma, Sunil K; Gupta, Vijay K; Sharma, Gainda L

    2012-06-01

    A synthetic coumarin, N,N,N-triethyl-11-(4-methyl-2-oxo-2H-chromen-7-yloxy)-11-oxoundecan-1-aminium bromide (SCD-1), having potent activity against pathogenic Aspergilli (MIC90 15.62 μg/mL), was investigated to identify its molecular targets in the pathogen. The proteome of Aspergillus fumigatus was developed after treatment with sublethal doses of compound and analyzed. The results demonstrated 143 differentially expressed proteins on treatment with SCD-1. The expression of four proteins, namely cell division control protein, ubiquitin-like activating enzyme, vacuolar ATP synthase catalytic subunit A, and UTP-glucose-1-phosphate uridylyltransferase of A. fumigatus, was completely inhibited, whereas there were 13 newly expressed and 96 overexpressed proteins, mainly belonging to stress pathway. The treatment of A. fumigatus with SCD-1 also led to attenuation of proteins involved in cell replication and other important biosynthetic processes, including riboflavin biosynthesis, which has been pathogen-specific. In addition to key enzymatic players and antioxidants, nine hypothetical proteins were also identified, seven of which have been novel, being described for the first time. As no cellular functions have yet been described for these hypothetical proteins, their alteration in response to SCD-1 provides significant information about their putative roles in pathogen defense.

  14. Mercury erosion experiments for spallation target system

    International Nuclear Information System (INIS)

    Kinoshita, Hidetaka; Kaminaga, Masanori; Haga, Katsuhiro; Hino, Ryutaro

    2003-01-01

    The Japan Atomic Energy Research Institute (JAERI) and the High Energy Accelerator Research Organization (KEK) are promoting a plan to construct the spallation neutron source at the Tokai Research Establishment, JAERI, under the High-Intensity Proton Accelerator Project (J-PARC). A mercury circulation system has been designed so as to supply mercury to the target stably under the rated flow rate of 41 m 3 /hr. Then, it was necessary to confirm a mercury pump performance from the viewpoint of making the mercury circulation system feasible, and more, to investigate erosion rate under the mercury flow as well as an amount of mercury remained on the surface after drain from the viewpoints of mechanical strength relating to the lifetime and remote handling of mercury components. The mercury pump performance was tested under the mercury flow conditions by using an experimental gear pump, which had almost the same structure as a practical mercury pump to be expected in the mercury circulation system, and the erosion rates in a mercury pipeline as well as the amount of mercury remained on the surface were also investigated. The discharged flow rates of the experimental gear pump increased linearly with the rotation speed, so that the gear pump would work as the flow meter. Erosion rates obtained under the mercury velocity less than 1.6 m/s was found to be so small that decrease of pipeline wall thickness would be 390 μm after 30-year operation under the rated mercury velocity of 0.7 m/s. For the amount of remaining mercury on the pipeline, remaining rates of weight and volume were estimated at 50.7 g/m 2 and 3.74 Hg-cm 3 /m 2 , respectively. Applying these remaining rates of weight and volume to the mercury target, the remaining mercury was estimated at about 106.5 g and 7.9 cm 3 . Radioactivity of this remaining mercury volume was found to be three-order lower than that of the target casing. (author)

  15. Electron beam facility for divertor target experiments

    International Nuclear Information System (INIS)

    Anisimov, A.; Gagen-Torn, V.; Giniyatulin, R.N.

    1994-01-01

    To test different concepts of divertor targets and bumpers an electron beam facility was assembled in Efremov Institute. It consists of a vacuum chamber (3m 3 ), vacuum pump, electron beam gun, manipulator to place and remove the samples, water loop and liquid metal loop. The following diagnostics of mock-ups is stipulated: (1) temperature distribution on the mock-up working surface (scanning pyrometer and infra-red imager); (2) temperature distribution over mocked-up thickness in 3 typical cross-sections (thermo-couples); (3) cracking dynamics during thermal cycling (acoustic-emission method), (4) defects in the mock-up before and after tests (ultra-sonic diagnostics, electron and optical microscopes). Carbon-based and beryllium mock-ups are made for experimental feasibility study of water and liquid-metal-cooled divertor/bumper concepts

  16. Proteomic Identification of Target Proteins of Thiodigalactoside in White Adipose Tissue from Diet-Induced Obese Rats

    Directory of Open Access Journals (Sweden)

    Hilal Ahmad Parray

    2015-06-01

    Full Text Available Previously, galectin-1 (GAL1 was found to be up-regulated in obesity-prone subjects, suggesting that use of a GAL1 inhibitor could be a novel therapeutic approach for treatment of obesity. We evaluated thiodigalactoside (TDG as a potent inhibitor of GAL1 and identified target proteins of TDG by performing comparative proteome analysis of white adipose tissue (WAT from control and TDG-treated rats fed a high fat diet (HFD using two dimensional gel electrophoresis (2-DE combined with MALDI-TOF-MS. Thirty-two spots from a total of 356 matched spots showed differential expression between control and TDG-treated rats, as identified by peptide mass fingerprinting. These proteins were categorized into groups such as carbohydrate metabolism, tricarboxylic acid (TCA cycle, signal transduction, cytoskeletal, and mitochondrial proteins based on functional analysis using Protein Annotation Through Evolutionary Relationship (PANTHER and Database for Annotation, Visualization, Integrated Discovery (DAVID classification. One of the most striking findings of this study was significant changes in Carbonic anhydrase 3 (CA3, Voltage-dependent anion channel 1 (VDAC1, phosphatidylethanolamine-binding protein 1 (PEBP1, annexin A2 (ANXA2 and lactate dehydrogenase A chain (LDHA protein levels between WAT from control and TDG-treated groups. In addition, we confirmed increased expression of thermogenic proteins as well as reduced expression of lipogenic proteins in response to TDG treatment. These results suggest that TDG may effectively prevent obesity, and TDG-responsive proteins can be used as novel target proteins for obesity treatment.

  17. Wetted foam liquid fuel ICF target experiments

    International Nuclear Information System (INIS)

    Olson, R E; Leeper, R J; Yi, S A; Kline, J L; Zylstra, A B; Peterson, R R; Shah, R; Braun, T; Biener, J; Kozioziemski, B J; Sater, J D; Biener, M M; Hamza, A V; Nikroo, A; Hopkins, L Berzak; Ho, D; LePape, S; Meezan, N B

    2016-01-01

    We are developing a new NIF experimental platform that employs wetted foam liquid fuel layer ICF capsules. We will use the liquid fuel layer capsules in a NIF sub-scale experimental campaign to explore the relationship between hot spot convergence ratio (CR) and the predictability of hot spot formation. DT liquid layer ICF capsules allow for flexibility in hot spot CR via the adjustment of the initial cryogenic capsule temperature and, hence, DT vapor density. Our hypothesis is that the predictive capability of hot spot formation is robust and 1D-like for a relatively low CR hot spot (CR∼15), but will become less reliable as hot spot CR is increased to CR>20. Simulations indicate that backing off on hot spot CR is an excellent way to reduce capsule instability growth and to improve robustness to low-mode x-ray flux asymmetries. In the initial experiments, we will test our hypothesis by measuring hot spot size, neutron yield, ion temperature, and burn width to infer hot spot pressure and compare to predictions for implosions with hot spot CR's in the range of 12 to 25. Larger scale experiments are also being designed, and we will advance from sub-scale to full-scale NIF experiments to determine if 1D-like behavior at low CR is retained as the scale-size is increased. The long-term objective is to develop a liquid fuel layer ICF capsule platform with robust thermonuclear burn, modest CR, and significant α-heating with burn propagation. (paper)

  18. Preliminary performance and ICF target experiments with Nova

    International Nuclear Information System (INIS)

    Drake, R.P.

    1985-11-01

    In December 1984, the Nova facility fired all ten laser arms, converted the output 1.05 micron energy to 0.35 micron light, and focused the 0.35 micron light through a 4 mm pinhole in the ten-beam target chamber. Since that time, a two-beam target chamber has been added, the performance of the laser evaluated, and preparation has been made for target experiments. This paper summarizes the performance of Nova and describes progress and plans for target experiments

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2012-04-01

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

  20. Targets with thin ferromagnetic layers for transient field experiments

    International Nuclear Information System (INIS)

    Gallant, J.L.; Dmytrenko, P.

    1982-01-01

    Multilayer targets containing a central layer sufficiently thin so that all recoil nuclei can traverse it and subsequently stop in a suitable cubic environment have been prepared. Such targets are required in experiments making use of a magnetic field acting on an ion moving through a ferromagnetic material. The preparation and annealing of the ferromagnetic foils (iron and gadolinium) and the fabrication of the multilayer targets are described. (orig.)

  1. Target bombardment by ion beams generated in the Focus experiment

    International Nuclear Information System (INIS)

    Bernard, Alain; Coudeville, Alain; Garconnet, J.-P.; Jolas, A.; Mascureau, J. de; Nazet, Christian.

    1976-01-01

    In a Mather-Focus experiment, it was shown that 80% of the neutron emitted were generated through bombardment. The apparatus was operated with various targets at a distance of 13mm from the anode. In the low pressure regime, a deuteron beam of high energy was produced. Its emission duration was measured using a CD 2 target [fr

  2. Proteomic amino-termini profiling reveals targeting information for protein import into complex plastids.

    Directory of Open Access Journals (Sweden)

    Pitter F Huesgen

    Full Text Available In organisms with complex plastids acquired by secondary endosymbiosis from a photosynthetic eukaryote, the majority of plastid proteins are nuclear-encoded, translated on cytoplasmic ribosomes, and guided across four membranes by a bipartite targeting sequence. In-depth understanding of this vital import process has been impeded by a lack of information about the transit peptide part of this sequence, which mediates transport across the inner three membranes. We determined the mature N-termini of hundreds of proteins from the model diatom Thalassiosira pseudonana, revealing extensive N-terminal modification by acetylation and proteolytic processing in both cytosol and plastid. We identified 63 mature N-termini of nucleus-encoded plastid proteins, deduced their complete transit peptide sequences, determined a consensus motif for their cleavage by the stromal processing peptidase, and found evidence for subsequent processing by a plastid methionine aminopeptidase. The cleavage motif differs from that of higher plants, but is shared with other eukaryotes with complex plastids.

  3. Differential proteomic analysis of Aspergillus fumigatus morphotypes reveals putative drug targets.

    Science.gov (United States)

    Kubitschek-Barreira, Paula H; Curty, Nathalia; Neves, Gabriela W P; Gil, Concha; Lopes-Bezerra, Leila M

    2013-01-14

    Aspergillus fumigatus is the main etiological agent of invasive aspergillosis, an important opportunistic infection for neutropenic patients. The main risk groups are patients with acute leukemia and bone marrow transplantation recipients. The lack of an early diagnostic test together with the limited spectrum of antifungal drugs remains a setback to the successful treatment of this disease. During invasive infection the inhaled fungal conidia enter the morphogenic cycle leading to angioinvasive hyphae. This work aimed to study differentially expressed proteins of A. fumigatus during morphogenesis. To achieve this goal, a 2D-DIGE approach was applied to study surface proteins extractable by reducing agents of two A. fumigatus morphotypes: germlings and hyphae. Sixty-three differentially expressed proteins were identified by MALDI-ToF/MS. We observed that proteins associated with biosynthetic pathways and proteins with multiple functions (miscellaneous) were over-expressed in the early stages of germination, while in hyphae, the most abundant proteins detected were related to metabolic processes or have unknown functions. Among the most interesting proteins regulated during morphogenesis, two putative drug targets were identified, the translational factor, eEF3 and the CipC-like protein. Neither of these proteins are present in mammalian cells. Copyright © 2012 Elsevier B.V. All rights reserved.

  4. Proteomics as a Tool to Identify New Targets Against Aspergillus and Scedosporium in the Context of Cystic Fibrosis.

    Science.gov (United States)

    Ramirez-Garcia, Andoni; Pellon, Aize; Buldain, Idoia; Antoran, Aitziber; Arbizu-Delgado, Aitana; Guruceaga, Xabier; Rementeria, Aitor; Hernando, Fernando L

    2018-02-01

    Cystic fibrosis (CF) is a genetic disorder that increases the risk of suffering microbial, including fungal, infections. In this paper, proteomics-based information was collated relating to secreted and cell wall proteins with potential medical applications from the most common filamentous fungi in CF, i.e., Aspergillus and Scedosporium/Lomentospora species. Among the Aspergillus fumigatus secreted allergens, β-1,3-endoglucanase, the alkaline protease 1 (Alp1/oryzin), Asp f 2, Asp f 13/15, chitinase, chitosanase, dipeptidyl-peptidase V (DppV), the metalloprotease Asp f 5, mitogillin/Asp f 1, and thioredoxin reductase receive a special mention. In addition, the antigens β-glucosidase 1, catalase, glucan endo-1,3-β-glucosidase EglC, β-1,3-glucanosyltransferases Gel1 and Gel2, and glutaminase A were also identified in secretomes of other Aspergillus species associated with CF: Aspergillus flavus, Aspergillus niger, Aspergillus nidulans, and Aspergillus terreus. Regarding cell wall proteins, cytochrome P450 and eEF-3 were proposed as diagnostic targets, and alkaline protease 2 (Alp2), Asp f 3 (putative peroxiredoxin pmp20), probable glycosidases Asp f 9/Crf1 and Crf2, GPI-anchored protein Ecm33, β-1,3-glucanosyltransferase Gel4, conidial hydrophobin Hyp1/RodA, and secreted aspartyl protease Pep2 as protective vaccines in A. fumigatus. On the other hand, for Scedosporium/Lomentospora species, the heat shock protein Hsp70 stands out as a relevant secreted and cell wall antigen. Additionally, the secreted aspartyl proteinase and an ortholog of Asp f 13, as well as the cell wall endo-1,3-β-D-glucosidase and 1,3-β-glucanosyl transferase, were also found to be significant proteins. In conclusion, proteins mentioned in this review may be promising candidates for developing innovative diagnostic and therapeutic tools for fungal infections in CF patients.

  5. PeptideManager: A Peptide Selection Tool for Targeted Proteomic Studies Involving Mixed Samples from Different Species

    Directory of Open Access Journals (Sweden)

    Kevin eDemeure

    2014-09-01

    Full Text Available The search for clinically useful protein biomarkers using advanced mass spectrometry approaches represents a major focus in cancer research. However, the direct analysis of human samples may be challenging due to limited availability, the absence of appropriate control samples, or the large background variability observed in patient material. As an alternative approach, human tumors orthotopically implanted into a different species (xenografts are clinically relevant models that have proven their utility in pre-clinical research. Patient derived xenografts for glioblastoma have been extensively characterized in our laboratory and have been shown to retain the characteristics of the parental tumor at the phenotypic and genetic level. Such models were also found to adequately mimic the behavior and treatment response of human tumors. The reproducibility of such xenograft models, the possibility to identify their host background and perform tumor-host interaction studies, are major advantages over the direct analysis of human samples.At the proteome level, the analysis of xenograft samples is challenged by the presence of proteins from two different species which, depending on tumor size, type or location, often appear at variable ratios. Any proteomics approach aimed at quantifying proteins within such samples must consider the identification of species specific peptides in order to avoid biases introduced by the host proteome. Here, we present an in-house methodology and tool developed to select peptides used as surrogates for protein candidates from a defined proteome (e.g., human in a host proteome background (e.g., mouse, rat suited for a mass spectrometry analysis. The tools presented here are applicable to any species specific proteome, provided a protein database is available. By linking the information from both proteomes, PeptideManager significantly facilitates and expedites the selection of peptides used as surrogates to analyze

  6. Design choices and issues in fixed-target B experiments

    International Nuclear Information System (INIS)

    Camilleri, L.

    1993-01-01

    The main priority of any experiment on B physics in the years to come will be an endeavour to observe CP violation in the B sector. Such measurements imply the following requirements of the experiment. Trigger: a muon trigger will be sensitive to J/ψ reactions and muon tags; an electron trigger will double the number of lepton events; in order to include kaon tags and self-tagging reactions, the experiment must not rely entirely on lepton triggers. Secondary Vertex triggers and hadron p T triggers should be included in order to have the maximum flexibility. Detector: vertex detector; particle identification; good momentum resolution; electromagnetic and hadronic calorimeters; muon detector. In addition the following issues have to be addressed: Collider or fixed-target mode? If fixed target, extracted beam or internal target? If internal target, gas jet or wire target? If a gas jet, hydrogen or a heavy gas? Beam pipe design. Silicon microvertex design and radiation damage. K s 0 decay path. Particle identification. Momentum resolution. Order of detectors. No single method stands out as the open-quotes obvious one.close quotes An extracted beam yields better vertex resolution and an internal target easier triggering. A flexible and diverse triggering scheme is of prime importance in order to be sensitive to as many reactions as possible, the experiment should not be limited to lepton triggers only. Proposed experiments (P867, HERA B) at existing machines will be invaluable for testing new devices and strategies for the LHC and SSC experiments

  7. Practical methods of target preparation for use in nuclear experiments

    International Nuclear Information System (INIS)

    Sugai, Isao.

    1976-01-01

    This is the fifth report on the practical methods of target preparation for use in nuclear experiments following the previous one (INS-J-152, 1975). Electro-deposition is a very powerful technique well suited to the preparation of self-supporting targets of Ni, Cr, Zn, Rh, Cd, Sb and Pb metals over a wide range of thickness from 1 to 20 mg/cm 2 . The uniformities of the thicknesses of Cr, Zn, Rh, Cd and Pb targets were measured with α- and β-ray thickness gauges. The impurities in Cr target were checked by the measurement of elastically scattered protons, and by a optical spectrometer. (auth.)

  8. Operational Experience of an Open-Access, Subscription-Based Mass Spectrometry and Proteomics Facility

    Science.gov (United States)

    Williamson, Nicholas A.

    2018-03-01

    This paper discusses the successful adoption of a subscription-based, open-access model of service delivery for a mass spectrometry and proteomics facility. In 2009, the Mass Spectrometry and Proteomics Facility at the University of Melbourne (Australia) moved away from the standard fee for service model of service provision. Instead, the facility adopted a subscription- or membership-based, open-access model of service delivery. For a low fixed yearly cost, users could directly operate the instrumentation but, more importantly, there were no limits on usage other than the necessity to share available instrument time with all other users. All necessary training from platform staff and many of the base reagents were also provided as part of the membership cost. These changes proved to be very successful in terms of financial outcomes for the facility, instrument access and usage, and overall research output. This article describes the systems put in place as well as the overall successes and challenges associated with the operation of a mass spectrometry/proteomics core in this manner. [Figure not available: see fulltext.

  9. Beauty and charm production in fixed target experiments

    International Nuclear Information System (INIS)

    Kidonakis, Nikolaos; Vogt, Ramona

    2004-01-01

    We present calculations of NNLO threshold corrections for beauty and charm production in π - p and pp interactions at fixed-target experiments. Recent calculations for heavy quark hadroproduction have included next-to-next-to-leading-order (NNLO) soft-gluon corrections [1] to the double differential cross section from threshold resummation techniques [2]. These corrections are important for near-threshold beauty and charm production at fixed-target experiments, including HERA-B and some of the current and future heavy ion experiments

  10. Target selection biases from recent experience transfer across effectors.

    Science.gov (United States)

    Moher, Jeff; Song, Joo-Hyun

    2016-02-01

    Target selection is often biased by an observer's recent experiences. However, not much is known about whether these selection biases influence behavior across different effectors. For example, does looking at a red object make it easier to subsequently reach towards another red object? In the current study, we asked observers to find the uniquely colored target object on each trial. Randomly intermixed pre-trial cues indicated the mode of action: either an eye movement or a visually guided reach movement to the target. In Experiment 1, we found that priming of popout, reflected in faster responses following repetition of the target color on consecutive trials, occurred regardless of whether the effector was repeated from the previous trial or not. In Experiment 2, we examined whether an inhibitory selection bias away from a feature could transfer across effectors. While priming of popout reflects both enhancement of the repeated target features and suppression of the repeated distractor features, the distractor previewing effect isolates a purely inhibitory component of target selection in which a previewed color is presented in a homogenous display and subsequently inhibited. Much like priming of popout, intertrial suppression biases in the distractor previewing effect transferred across effectors. Together, these results suggest that biases for target selection driven by recent trial history transfer across effectors. This indicates that representations in memory that bias attention towards or away from specific features are largely independent from their associated actions.

  11. A Feasibility Experiment of a W-powder Target

    CERN Multimedia

    Charitonidis, N; Carreta, O; Densham, C; Davenne, T; Fabich, A; Loveridge, P; Rivkin, L

    2014-01-01

    The development of high‐power targets remains a key R&D activity for future facilities presently under study like the Neutrino Factory, Muon Collider or upgraded high‐ power super beams for long‐baseline neutrino experiments.  The choice of materials to sustain the beam power ranging up to MW levels is not trivial. Granular solid targets have been proposed and are being studied as a candidate for such high‐power target systems. In the recently commissioned HiRadMat facility at CERN, a feasibility  experiment of a tungsten powder target was performed. The experiment was designed to explore for first time the impact of a high‐power proton beam on a static W-powder target in a thimble configuration. The diagnostics of the experiment were based on remote high speed photography as well as on laser‐doppler vibration measurements of the target containers. Results from the experimental findings are presented ...

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

    Science.gov (United States)

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

    2014-12-05

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

  13. A targeted proteomics approach to the quantitative analysis of ERK/Bcl-2-mediated anti-apoptosis and multi-drug resistance in breast cancer.

    Science.gov (United States)

    Yang, Ting; Xu, Feifei; Sheng, Yuan; Zhang, Wen; Chen, Yun

    2016-10-01

    Apoptosis suppression caused by overexpression of anti-apoptotic proteins is a central factor to the acquisition of multi-drug resistance (MDR) in breast cancer. As a highly conserved anti-apoptotic protein, Bcl-2 can initiate an anti-apoptosis response via an ERK1/2-mediated pathway. However, the details therein are still far from completely understood and a quantitative description of the associated proteins in the biological context may provide more insights into this process. Following our previous attempts in the quantitative analysis of MDR mechanisms, liquid chromatography-tandem mass spectrometry (LC-MS/MS)-based targeted proteomics was continually employed here to describe ERK/Bcl-2-mediated anti-apoptosis. A targeted proteomics assay was developed and validated first for the simultaneous quantification of ERK1/2 and Bcl-2. In particular, ERK isoforms (i.e., ERK1 and ERK2) and their differential phosphorylated forms including isobaric ones were distinguished. Using this assay, differential protein levels and site-specific phosphorylation stoichiometry were observed in parental drug-sensitive MCF-7/WT cancer cells and drug-resistant MCF-7/ADR cancer cells and breast tissue samples from two groups of patients who were either suspected or diagnosed to have drug resistance. In addition, quantitative analysis of the time course of both ERK1/2 and Bcl-2 in doxorubicin (DOX)-treated MCF-7/WT cells confirmed these findings. Overall, we propose that targeted proteomics can be used generally to resolve more complex cellular events.

  14. The primary target for the hypernuclear experiment at PANDA

    Energy Technology Data Exchange (ETDEWEB)

    Bleser, Sebastian; Martinez Rojo, Marta; Sanchez Lorente, Alicia; Steinen, Marcell [Helmholtz-Institut Mainz (Germany); Iazzi, Felice [INFN, Torino (Italy); Politecnico di Torino (Italy); Pochodzalla, Josef [Helmholtz-Institut Mainz (Germany); Institut fuer Kernphysik, JGU Mainz (Germany); Rausch, Nicolas [Institut fuer Kernphysik, JGU Mainz (Germany); Collaboration: PANDA-Collaboration

    2016-07-01

    A key aspect of the PANDA experiment at the future FAIR facility is the production and spectroscopy of ΛΛ hypernuclei. The double hypernuclei are produced in a two-stage target system consisting of a primary in-beam filament to produce low momentum Ξ{sup -} hyperons which are stopped and converted into two Λ hyperons in a secondary external target. A system of piezo motors will be used to steer the primary target in two dimensions. This allows to achieve a constant luminosity by adjusting the position and provides the replacement of eventually broken target wires. The poster shows the mechanical integration of this system within the vacuum chamber attached to the beampipe. Its motion is controlled using the EPICS framework as planned for PANDA. In addition the results of radiation tests with foreseen target wires are presented.

  15. Review of calorimetry in Fermilab fixed-target experiments

    International Nuclear Information System (INIS)

    Crisler, M.B.

    1995-04-01

    The fixed-target program at Fermilab comprises as many as thirteen simultaneous experiments in ten separate beamlines using beams of primary protons, pions, kaons, electrons, neutrinos, and muons. The fixed target beamlines were last in operation in the latter half of 1991, shutting down in 1992. The next fixed target run is scheduled for early 1996. This article describes some of the wide variety of calorimetric devices that were in use in the past run or to be used in the coming run. Special attention is devoted to the new devices currently under construction

  16. Reproducibility and consistency of proteomic experiments on natural populations of a non-model aquatic insect.

    Science.gov (United States)

    Hidalgo-Galiana, Amparo; Monge, Marta; Biron, David G; Canals, Francesc; Ribera, Ignacio; Cieslak, Alexandra

    2014-01-01

    Population proteomics has a great potential to address evolutionary and ecological questions, but its use in wild populations of non-model organisms is hampered by uncontrolled sources of variation. Here we compare the response to temperature extremes of two geographically distant populations of a diving beetle species (Agabus ramblae) using 2-D DIGE. After one week of acclimation in the laboratory under standard conditions, a third of the specimens of each population were placed at either 4 or 27°C for 12 h, with another third left as a control. We then compared the protein expression level of three replicated samples of 2-3 specimens for each treatment. Within each population, variation between replicated samples of the same treatment was always lower than variation between treatments, except for some control samples that retained a wider range of expression levels. The two populations had a similar response, without significant differences in the number of protein spots over- or under-expressed in the pairwise comparisons between treatments. We identified exemplary proteins among those differently expressed between treatments, which proved to be proteins known to be related to thermal response or stress. Overall, our results indicate that specimens collected in the wild are suitable for proteomic analyses, as the additional sources of variation were not enough to mask the consistency and reproducibility of the response to the temperature treatments.

  17. Tools for monitoring system suitability in LC MS/MS centric proteomic experiments.

    Science.gov (United States)

    Bereman, Michael S

    2015-03-01

    With advances in liquid chromatography coupled to tandem mass spectrometry technologies combined with the continued goals of biomarker discovery, clinical applications of established biomarkers, and integrating large multiomic datasets (i.e. "big data"), there remains an urgent need for robust tools to assess instrument performance (i.e. system suitability) in proteomic workflows. To this end, several freely available tools have been introduced that monitor a number of peptide identification (ID) and/or peptide ID free metrics. Peptide ID metrics include numbers of proteins, peptides, or peptide spectral matches identified from a complex mixture. Peptide ID free metrics include retention time reproducibility, full width half maximum, ion injection times, and integrated peptide intensities. The main driving force in the development of these tools is to monitor both intra- and interexperiment performance variability and to identify sources of variation. The purpose of this review is to summarize and evaluate these tools based on versatility, automation, vendor neutrality, metrics monitored, and visualization capabilities. In addition, the implementation of a robust system suitability workflow is discussed in terms of metrics, type of standard, and frequency of evaluation along with the obstacles to overcome prior to incorporating a more proactive approach to overall quality control in liquid chromatography coupled to tandem mass spectrometry based proteomic workflows. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  18. Event Display for the Fixed Target Experiment BM@N

    Directory of Open Access Journals (Sweden)

    Gertsenberger Konstantin

    2016-01-01

    Full Text Available One of the main problems to be solved in modern high energy physics experiments on particle collisions with a fixed target is the visual representation of the events during the experiment run. The article briefly describes the structure of the BM@N facility at the Nuclotron being under construction at the Joint Institute for Nuclear Research with the aim to study properties of the baryonic matter in collisions of ions with fixed target at energies up to 4 GeV/nucleon (for Au79+. Aspects concerning the visualization of data and detector details at the modern experiments and possibilities of practical applications are discussed. We present event display system intended to visualize the detector geometries and events of particle collisions with the fixed target, its options and features as well as integration with BMNRoot software. The examples of graphical representation of simulated and reconstructed points and particle tracks with BM@N geometry are given for central collisions of Au79+ ions with gold target and deuterons with carbon target.

  19. Introduction to charm decay analysis in fixed target experiments

    Energy Technology Data Exchange (ETDEWEB)

    Bediaga, Ignacio; Goebel, Carla

    1996-01-01

    We present an introduction to data analysis in Experimental High Energy Physics, and some concepts and useful tools are discussed. To illustrate, we use the data of E-791, a fixed target experiment recently realized at Fermilab. In particular, we analyse decay modes of D{sup +} meson with three charged particles in the final state. (author). 8 refs., 22 figs., 1 tab.

  20. Recent heavy flavor physics results from fixed target experiments

    International Nuclear Information System (INIS)

    Spiegel, L.

    1991-11-01

    Recent results from fixed target experiments in the field of heavy quark flavors, as published or otherwise disseminated in the last year, are reviewed. Emphasis is placed on distilling the main conclusions from these results. 35 refs., 5 figs., 4 tabs

  1. Recent heavy flavor physics results from fixed target experiments

    Energy Technology Data Exchange (ETDEWEB)

    Spiegel, L.

    1991-11-01

    Recent results from fixed target experiments in the field of heavy quark flavors, as published or otherwise disseminated in the last year, are reviewed. Emphasis is placed on distilling the main conclusions from these results. 35 refs., 5 figs., 4 tabs.

  2. Testing light dark matter coannihilation with fixed-target experiments

    Energy Technology Data Exchange (ETDEWEB)

    Izaguirre, Eder; Kahn, Yonatan; Krnjaic, Gordan; Moschella, Matthew

    2017-09-01

    In this paper, we introduce a novel program of fixed-target searches for thermal-origin Dark Matter (DM), which couples inelastically to the Standard Model. Since the DM only interacts by transitioning to a heavier state, freeze-out proceeds via coannihilation and the unstable heavier state is depleted at later times. For sufficiently large mass splittings, direct detection is kinematically forbidden and indirect detection is impossible, so this scenario can only be tested with accelerators. Here we propose new searches at proton and electron beam fixed-target experiments to probe sub-GeV coannihilation, exploiting the distinctive signals of up- and down-scattering as well as decay of the excited state inside the detector volume. We focus on a representative model in which DM is a pseudo-Dirac fermion coupled to a hidden gauge field (dark photon), which kinetically mixes with the visible photon. We define theoretical targets in this framework and determine the existing bounds by reanalyzing results from previous experiments. We find that LSND, E137, and BaBar data already place strong constraints on the parameter space consistent with a thermal freeze-out origin, and that future searches at Belle II and MiniBooNE, as well as recently-proposed fixed-target experiments such as LDMX and BDX, can cover nearly all remaining gaps. We also briefly comment on the discovery potential for proposed beam dump and neutrino experiments which operate at much higher beam energies.

  3. Introduction to charm decay analysis in fixed target experiments

    International Nuclear Information System (INIS)

    Bediaga, Ignacio; Goebel, Carla.

    1996-01-01

    We present an introduction to data analysis in Experimental High Energy Physics, and some concepts and useful tools are discussed. To illustrate, we use the data of E-791, a fixed target experiment recently realized at Fermilab. In particular, we analyse decay modes of D + meson with three charged particles in the final state. (author). 8 refs., 22 figs., 1 tab

  4. Data from a targeted proteomics approach to discover biomarkers in saliva for the clinical diagnosis of periodontitis

    Directory of Open Access Journals (Sweden)

    V. Orti

    2018-06-01

    Full Text Available This study focused on the search for new biomarkers based on liquid chromatography-multiple reaction monitoring (LC-MRM proteomics profiling of whole saliva from patients with periodontitis compared to healthy subjects. The LC-MRM profiling approach is a new and innovative method that has already been validated for the absolute and multiplexed quantification of biomarkers in several diseases. The dataset for this study was produced using LC-MRM to monitor protein levels in a multiplex assay, it provides clinical information on salivary biomarkers of periodontitis. The data presented here is an extension of our recently published research article (Mertens et al., 2017 [1]. Keywords: Clinical chemistry, Mass spectrometry, Proteomics, Saliva biochemistry, Oral disease, Periodontitis

  5. Thermal experiments in the model of ADS target

    International Nuclear Information System (INIS)

    Alexander, Efanov; Yuri, Orlov; Alexander, Sorokin; Eugeni, Ivanov; Galina, Bogoslovskaia; Ning, Li

    2002-01-01

    The paper presents thermal experiments performed in the SSC RF IPPE on the ADS window target model. Brief description of the model, specific features of structure, measurement system and some methodological approaches are presented. Eutectic lead-bismuth alloy is modeled here by eutectic sodium-potassium alloy. The following characteristics of the target model were measured directly and estimated by processing: coolant flow rate, model power, absolute temperature of the coolant with a distance from the membrane of the target, absolute temperature of the membrane surface, mean square value and pulsating component of coolant temperature, as well as membrane temperature. Measurements have shown a great pulsations of temperature existing at the membrane surface that must be taken into account in analysis of strength of real target system. Experimental temperature fields (present work) and velocity fields measured earlier make up a complete database for verification of 2D and 3D thermohydraulic codes. (author)

  6. A Proteomic Screen Identified Stress-Induced Chaperone Proteins as Targets of Akt Phosphorylation in Mesangial Cells

    OpenAIRE

    Barati, Michelle T.; Rane, Madhavi J.; Klein, Jon B.; McLeish, Kenneth R.

    2006-01-01

    The serine-threonine kinase Akt regulates mesangial cell apoptosis, proliferation, and hypertrophy. To define Akt signaling pathways in mesangial cells, we performed a functional proteomic screen for rat mesangial cell proteins phosphorylated by Akt. A group of chaperone proteins, heat shock protein (Hsp) 70, Hsp90α, Hsp90β, Glucose-regulated protein (Grp) Grp78, Grp94, and protein disulfide isomerase (PDI) were identified as potential Akt substrates by two techniques: (a) in vitro phosphoryl...

  7. Prospects of polarized fixed target Drell-Yan experiments

    International Nuclear Information System (INIS)

    Liu, M X; Jiang, X; Crabb, D G; Chen, J P; Bai, M

    2011-01-01

    It has been proposed that the Siverse transverse single spin asymmetry in Drell-Yan production in transversely polarized p+p collisions would have an opposite sign compared to what has been observed in the polarized Semi-Inclusive Deep Inelastic Scattering (SIDIS) experiments. Experimental confirmation or disproval of this prediction would provide a novel fundamental test of QCD and shed new light on our theoretical understanding of the transverse spin physics phenomena. We discuss the prospects and physics sensitivities of polarized fixed target Drell-Yan experiments that could utilize the existing proton and other hadron beams at Fermilab, and polarized proton beams at RHIC with a polarized solid proton and/or neutron target option. We show that if realized, the new experiments would provide critical measurements of not only the sign change (or not) of Sivers functions, but also the information of quark and antiquark's Sivers distributions over a wide kinematic range.

  8. Mining the nucleus accumbens proteome for novel targets of alcohol self-administration in male C57BL/6J mice.

    Science.gov (United States)

    Faccidomo, Sara; Swaim, Katarina S; Saunders, Briana L; Santanam, Taruni S; Taylor, Seth M; Kim, Michelle; Reid, Grant T; Eastman, Vallari R; Hodge, Clyde W

    2018-03-03

    There is a clear need for discovery of effective medications to treat behavioral pathologies associated with alcohol addiction, such as chronic drinking. The goal of this preclinical study was to assess effects of chronic alcohol drinking on the nucleus accumbens (NAcb) proteome to identify and validate novel targets for medications development. Two-dimensional difference in-gel electrophoresis (2D-DIGE) with matrix-assisted laser desorption ionization tandem time-of-flight (MALDI-TOF/TOF) was used to assess effects of chronic voluntary home-cage (24-h access) alcohol drinking on the NAcb proteome of C57BL/6J mice. To extend these findings to a model of alcohol self-administration and reinforcement, we investigated potential regulation of the positive reinforcing effects of alcohol by the target protein glutathione S-transferase Pi 1 (GSTP1) using a pharmacological inhibition strategy in mice trained to self-administer alcohol or sucrose. Expression of 52 unique proteins in the NAcb was changed by chronic alcohol drinking relative to water control (23 upregulated, 29 downregulated). Ingenuity Pathway Analysis showed that alcohol drinking altered an array of protein networks associated with neurological and psychological disorders, molecular and cellular functions, and physiological systems and development. DAVID functional annotation analysis identified 9 proteins (SNCA, GSTP1, PRDX3, PPP3R1, EIF5A, PHB, PEBP1/RKIP, GAPDH, AND SOD1) that were significantly overrepresented in a functional cluster that included the Gene Ontology categories "response to alcohol" and "aging." Immunoblots confirmed changes in Pebp1 (RKIP) and GSTP1 in NAcb with no change in amygdala or frontal cortex, suggesting anatomical specificity. Systemic inhibition of GSTP1 with Ezatiostat (0-30 mg/kg, i.p.) dose-dependently reduced the reinforcing effects of alcohol as measured by operant self-administration, in the absence of motor effects. Sucrose self-administration was also reduced but in a

  9. Nanodiamond targets for accelerator X-ray experiments

    Energy Technology Data Exchange (ETDEWEB)

    Lobko, A., E-mail: lobko@inp.bsu.by [Research Institute for Nuclear Problems, 11 Bobrujskaya Str., Minsk 220030 (Belarus); Golubeva, E. [Belarusian State University, 4 Nezavisimosti Prosp., Minsk 220030 (Belarus); Kuzhir, P.; Maksimenko, S. [Research Institute for Nuclear Problems, 11 Bobrujskaya Str., Minsk 220030 (Belarus); Ryazan State RadioEngineering University, 59/1 Gagarina Street, Ryazan 390005 (Russian Federation); Paddubskaya, A. [Research Institute for Nuclear Problems, 11 Bobrujskaya Str., Minsk 220030 (Belarus); Shenderova, O. [International Technology Center, 8100 Brownleigh Dr., S. 120, Raleigh, NC 27617 (United States); Uglov, V. [Belarusian State University, 4 Nezavisimosti Prosp., Minsk 220030 (Belarus); Valynets, N. [Research Institute for Nuclear Problems, 11 Bobrujskaya Str., Minsk 220030 (Belarus)

    2015-07-15

    Results of fabrication of a nanodiamond target for accelerator X-ray experiments are reported. Nanodiamond film with dimensions 5 × 7 mm and thickness of 500 nm has been made of the high pressure high temperature nanodiamonds using a filtration method. The average crystallite size of primary nanodiamond particles varies around 100 nm. Source nanodiamonds and fabricated nanodiamond film were characterized using Raman spectroscopy, electron microscopy, and X-ray diffractometry. Preliminary results show that targets made of nanodiamonds are perspective in generating crystal-assisted radiation by the relativistic charged particles, such as parametric X-rays, diffracted transition radiation, diffracted Bremsstrahlung, etc.

  10. Nanodiamond targets for accelerator X-ray experiments

    International Nuclear Information System (INIS)

    Lobko, A.; Golubeva, E.; Kuzhir, P.; Maksimenko, S.; Paddubskaya, A.; Shenderova, O.; Uglov, V.; Valynets, N.

    2015-01-01

    Results of fabrication of a nanodiamond target for accelerator X-ray experiments are reported. Nanodiamond film with dimensions 5 × 7 mm and thickness of 500 nm has been made of the high pressure high temperature nanodiamonds using a filtration method. The average crystallite size of primary nanodiamond particles varies around 100 nm. Source nanodiamonds and fabricated nanodiamond film were characterized using Raman spectroscopy, electron microscopy, and X-ray diffractometry. Preliminary results show that targets made of nanodiamonds are perspective in generating crystal-assisted radiation by the relativistic charged particles, such as parametric X-rays, diffracted transition radiation, diffracted Bremsstrahlung, etc

  11. Evaluation of a Genome-Scale In Silico Metabolic Model for Geobacter metallireducens by Using Proteomic Data from a Field Biostimulation Experiment

    Science.gov (United States)

    Fang, Yilin; Yabusaki, Steven B.; Lipton, Mary S.; Long, Philip E.

    2012-01-01

    Accurately predicting the interactions between microbial metabolism and the physical subsurface environment is necessary to enhance subsurface energy development, soil and groundwater cleanup, and carbon management. This study was an initial attempt to confirm the metabolic functional roles within an in silico model using environmental proteomic data collected during field experiments. Shotgun global proteomics data collected during a subsurface biostimulation experiment were used to validate a genome-scale metabolic model of Geobacter metallireducens—specifically, the ability of the metabolic model to predict metal reduction, biomass yield, and growth rate under dynamic field conditions. The constraint-based in silico model of G. metallireducens relates an annotated genome sequence to the physiological functions with 697 reactions controlled by 747 enzyme-coding genes. Proteomic analysis showed that 180 of the 637 G. metallireducens proteins detected during the 2008 experiment were associated with specific metabolic reactions in the in silico model. When the field-calibrated Fe(III) terminal electron acceptor process reaction in a reactive transport model for the field experiments was replaced with the genome-scale model, the model predicted that the largest metabolic fluxes through the in silico model reactions generally correspond to the highest abundances of proteins that catalyze those reactions. Central metabolism predicted by the model agrees well with protein abundance profiles inferred from proteomic analysis. Model discrepancies with the proteomic data, such as the relatively low abundances of proteins associated with amino acid transport and metabolism, revealed pathways or flux constraints in the in silico model that could be updated to more accurately predict metabolic processes that occur in the subsurface environment. PMID:23042184

  12. ProteomicsDB.

    Science.gov (United States)

    Schmidt, Tobias; Samaras, Patroklos; Frejno, Martin; Gessulat, Siegfried; Barnert, Maximilian; Kienegger, Harald; Krcmar, Helmut; Schlegl, Judith; Ehrlich, Hans-Christian; Aiche, Stephan; Kuster, Bernhard; Wilhelm, Mathias

    2018-01-04

    ProteomicsDB (https://www.ProteomicsDB.org) is a protein-centric in-memory database for the exploration of large collections of quantitative mass spectrometry-based proteomics data. ProteomicsDB was first released in 2014 to enable the interactive exploration of the first draft of the human proteome. To date, it contains quantitative data from 78 projects totalling over 19k LC-MS/MS experiments. A standardized analysis pipeline enables comparisons between multiple datasets to facilitate the exploration of protein expression across hundreds of tissues, body fluids and cell lines. We recently extended the data model to enable the storage and integrated visualization of other quantitative omics data. This includes transcriptomics data from e.g. NCBI GEO, protein-protein interaction information from STRING, functional annotations from KEGG, drug-sensitivity/selectivity data from several public sources and reference mass spectra from the ProteomeTools project. The extended functionality transforms ProteomicsDB into a multi-purpose resource connecting quantification and meta-data for each protein. The rich user interface helps researchers to navigate all data sources in either a protein-centric or multi-protein-centric manner. Several options are available to download data manually, while our application programming interface enables accessing quantitative data systematically. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

  13. Modelling hot electron generation in short pulse target heating experiments

    Directory of Open Access Journals (Sweden)

    Sircombe N.J.

    2013-11-01

    Full Text Available Target heating experiments planned for the Orion laser facility, and electron beam driven fast ignition schemes, rely on the interaction of a short pulse high intensity laser with dense material to generate a flux of energetic electrons. It is essential that the characteristics of this electron source are well known in order to inform transport models in radiation hydrodynamics codes and allow effective evaluation of experimental results and forward modelling of future campaigns. We present results obtained with the particle in cell (PIC code EPOCH for realistic target and laser parameters, including first and second harmonic light. The hot electron distributions are characterised and their implications for onward transport and target heating are considered with the aid of the Monte-Carlo transport code THOR.

  14. Experiment of ambient temperature distribution in ICF driver's target building

    International Nuclear Information System (INIS)

    Zhou Yi; He Jie; Yang Shujuan; Zhang Junwei; Zhou Hai; Feng Bin; Xie Na; Lin Donghui

    2009-01-01

    An experiment is designed to explore the ambient temperature distribution in an ICF driver's target building, Multi-channel PC-2WS temperature monitoring recorders and PTWD-2A precision temperature sensors are used to measure temperatures on the three vertical cross-sections in the building, and the collected data have been handled by MATLAB. The experiment and analysis show that the design of the heating ventilation and air conditioning (HVAC) system can maintain the temperature stability throughout the building. However, because of the impact of heat in the target chamber, larger local environmental temperature gradients appear near the marshalling yard, the staff region on the middle floor, and equipments on the lower floor which needs to be controlled. (authors)

  15. A super fixed target beauty experiment at the SSC

    International Nuclear Information System (INIS)

    Spiegel, L.; Murphy, C.T.; Cox, B.; Arenton, M.; Conetti, S.; Corti, G.; Dukes, C.; Golovatyuk, V.; Lawry, T.; McManus, A.

    1993-01-01

    The observation and precision measurement of CP violation asymmetries and the phase of the CKM matrix is a major objective of B experiments at the SSC. The yields of reconstructed and tagged B decays and the various factors which minimize the dilution factors make measurements of CP asymmetries in the fixed target option known as the SFT more than competitive with much more expensive hadron collider experiments and significantly better than asymmetric e + e - B factories. Moreover, the superior time resolution possible in the SFT configuration allows a precision in the measurement of the CKM matrix element phases possible with the SFT option for various B decay modes

  16. Hadron identification in a fixed target experiment at the SSC

    International Nuclear Information System (INIS)

    Nelson, K.S.; Cox, B.

    1993-01-01

    This article presents the design criteria and expected performance of a hadron identification system in a fixed target experiment at the SSC. The proposed SFT spectrometer will be used as a model for the discussion. Two primary uses of hadron identification is a B physics experiment are flavor tagging and the rejection of background due to particle reflections in the reconstruction of exclusive decay modes. In the first case it is shown that use of kaons can increase substantially the number of events which can be tagged. In the latter case, decays in which particles are mis-identified can form a background to a desired decay mode

  17. Targeting Inflation in a Dollarized Economy: The Peruvian Experience

    OpenAIRE

    Adrián Armas; Francisco Grippa

    2005-01-01

    This discusses the unique experience of Peru`s Central Bank with inflation targeting in an economy characterized by a high degree of financial dollarization. The paper outlines how Peru has taken financial dollarization into consideration in the design of monetary policy, then deals with monetary policy implementation and the Central Bank`s strategy for controlling financial dollarization risks. The paper concludes with analysis and lessons drawn from the Peruvian case.

  18. 2DB: a Proteomics database for storage, analysis, presentation, and retrieval of information from mass spectrometric experiments.

    Science.gov (United States)

    Allmer, Jens; Kuhlgert, Sebastian; Hippler, Michael

    2008-07-07

    The amount of information stemming from proteomics experiments involving (multi dimensional) separation techniques, mass spectrometric analysis, and computational analysis is ever-increasing. Data from such an experimental workflow needs to be captured, related and analyzed. Biological experiments within this scope produce heterogenic data ranging from pictures of one or two-dimensional protein maps and spectra recorded by tandem mass spectrometry to text-based identifications made by algorithms which analyze these spectra. Additionally, peptide and corresponding protein information needs to be displayed. In order to handle the large amount of data from computational processing of mass spectrometric experiments, automatic import scripts are available and the necessity for manual input to the database has been minimized. Information is in a generic format which abstracts from specific software tools typically used in such an experimental workflow. The software is therefore capable of storing and cross analysing results from many algorithms. A novel feature and a focus of this database is to facilitate protein identification by using peptides identified from mass spectrometry and link this information directly to respective protein maps. Additionally, our application employs spectral counting for quantitative presentation of the data. All information can be linked to hot spots on images to place the results into an experimental context. A summary of identified proteins, containing all relevant information per hot spot, is automatically generated, usually upon either a change in the underlying protein models or due to newly imported identifications. The supporting information for this report can be accessed in multiple ways using the user interface provided by the application. We present a proteomics database which aims to greatly reduce evaluation time of results from mass spectrometric experiments and enhance result quality by allowing consistent data handling

  19. 2DB: a Proteomics database for storage, analysis, presentation, and retrieval of information from mass spectrometric experiments

    Directory of Open Access Journals (Sweden)

    Hippler Michael

    2008-07-01

    Full Text Available Abstract Background The amount of information stemming from proteomics experiments involving (multi dimensional separation techniques, mass spectrometric analysis, and computational analysis is ever-increasing. Data from such an experimental workflow needs to be captured, related and analyzed. Biological experiments within this scope produce heterogenic data ranging from pictures of one or two-dimensional protein maps and spectra recorded by tandem mass spectrometry to text-based identifications made by algorithms which analyze these spectra. Additionally, peptide and corresponding protein information needs to be displayed. Results In order to handle the large amount of data from computational processing of mass spectrometric experiments, automatic import scripts are available and the necessity for manual input to the database has been minimized. Information is in a generic format which abstracts from specific software tools typically used in such an experimental workflow. The software is therefore capable of storing and cross analysing results from many algorithms. A novel feature and a focus of this database is to facilitate protein identification by using peptides identified from mass spectrometry and link this information directly to respective protein maps. Additionally, our application employs spectral counting for quantitative presentation of the data. All information can be linked to hot spots on images to place the results into an experimental context. A summary of identified proteins, containing all relevant information per hot spot, is automatically generated, usually upon either a change in the underlying protein models or due to newly imported identifications. The supporting information for this report can be accessed in multiple ways using the user interface provided by the application. Conclusion We present a proteomics database which aims to greatly reduce evaluation time of results from mass spectrometric experiments and enhance

  20. A comprehensive target selectivity survey of the BCR-ABL kinase inhibitor INNO-406 by kinase profiling and chemical proteomics in chronic myeloid leukemia cells.

    Science.gov (United States)

    Rix, U; Remsing Rix, L L; Terker, A S; Fernbach, N V; Hantschel, O; Planyavsky, M; Breitwieser, F P; Herrmann, H; Colinge, J; Bennett, K L; Augustin, M; Till, J H; Heinrich, M C; Valent, P; Superti-Furga, G

    2010-01-01

    Resistance to the BCR-ABL tyrosine kinase inhibitor imatinib poses a pressing challenge in treating chronic myeloid leukemia (CML). This resistance is often caused by point mutations in the ABL kinase domain or by overexpression of LYN. The second-generation BCR-ABL inhibitor INNO-406 is known to inhibit most BCR-ABL mutants and LYN efficiently. Knowledge of its full target spectrum would provide the molecular basis for potential side effects or suggest novel therapeutic applications and possible combination therapies. We have performed an unbiased chemical proteomics native target profile of INNO-406 in CML cells combined with functional assays using 272 recombinant kinases thereby identifying several new INNO-406 targets. These include the kinases ZAK, DDR1/2 and various ephrin receptors. The oxidoreductase NQO2, inhibited by both imatinib and nilotinib, is not a relevant target of INNO-406. Overall, INNO-406 has an improved activity over imatinib but a slightly broader target profile than both imatinib and nilotinib. In contrast to dasatinib and bosutinib, INNO-406 does not inhibit all SRC kinases and most TEC family kinases and is therefore expected to elicit fewer side effects. Altogether, these properties may make INNO-406 a valuable component in the drug arsenal against CML.

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

    Science.gov (United States)

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

    2015-06-03

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

  2. Generation of accurate peptide retention data for targeted and data independent quantitative LC-MS analysis: Chromatographic lessons in proteomics.

    Science.gov (United States)

    Krokhin, Oleg V; Spicer, Vic

    2016-12-01

    The emergence of data-independent quantitative LC-MS/MS analysis protocols further highlights the importance of high-quality reproducible chromatographic procedures. Knowing, controlling and being able to predict the effect of multiple factors that alter peptide RP-HPLC separation selectivity is critical for successful data collection for the construction of ion libraries. Proteomic researchers have often regarded RP-HPLC as a "black box", while vast amount of research on peptide separation is readily available. In addition to obvious parameters, such as the type of ion-pairing modifier, stationary phase and column temperature, we describe the "mysterious" effects of gradient slope, column size and flow rate on peptide separation selectivity. Retention time variations due to these parameters are governed by the linear solvent strength (LSS) theory on a peptide level by the value of its slope S in the basic LSS equation-a parameter that can be accurately predicted. Thus, the application of shallower gradients, higher flow rates, or smaller columns will each increases the relative retention of peptides with higher S-values (long species with multiple positively charged groups). Simultaneous changes to these parameters that each drive shifts in separation selectivity in the same direction should be avoided. The unification of terminology represents another pressing issue in this field of applied proteomics that should be addressed to facilitate further progress. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  3. On the configuration of an active target for a fixed-target B experiment at SSC energies

    International Nuclear Information System (INIS)

    Dukes, E.C.

    1993-01-01

    The optimal configuration of target and silicon microvertex detector for fixed-target B experiments has yet to be determined. For fixed-target charm experiments the usual setup consists of a series of inert target foils - typically a few millimeters thick and separated by a few centimeters - immediately followed by a silicon microvertex detector. Because of the larger boost at the SSC, the efficacy of using active target foils - tightly packed silicon microstrip detectors - has been considered by at least one group: the SFT collaboration. It is hoped that with an active target the tracks of charged B's themselves can be measured, improving charged B reconstruction efficiencies. The author examines two issues concerning silicon active targets for fixed-target experiments at the SSC: (1) the effect on the acceptance of the requirement that the B decay vertices occur outside of the target foils, and (2) the ability of an active target to directly track charged B's

  4. Target designs for energetics experiments on the National Ignition Facility

    International Nuclear Information System (INIS)

    Meezan, N B; Glenzer, S H; Suter, L J

    2008-01-01

    The goal of the first hohlraum energetics experiments on the National Ignition Facility (NIF) [G. H. Miller et al, Optical Eng. 43, 2841 (2004)] is to select the hohlraum design for the first ignition experiments. Sub-scale hohlraums heated by 96 of the 192 laser beams on the NIF are used to emulate the laser-plasma interaction behavior of ignition hohlraums. These 'plasma emulator' targets are 70% scale versions of the 1.05 MJ, 300 eV ignition hohlraum and have the same energy-density as the full-scale ignition designs. Radiation-hydrodynamics simulations show that the sub-scale target is a good emulator of plasma conditions inside the ignition hohlraum, reproducing density n e within 10% and temperature T e within 15% along a laser beam path. Linear backscatter gain analysis shows the backscatter risk to be comparable to that of the ignition target. A successful energetics campaign will allow the National Ignition Campaign to focus its efforts on optimizing ignition hohlraums with efficient laser coupling

  5. Proteomics dataset

    DEFF Research Database (Denmark)

    Bennike, Tue Bjerg; Carlsen, Thomas Gelsing; Ellingsen, Torkell

    2017-01-01

    The datasets presented in this article are related to the research articles entitled “Neutrophil Extracellular Traps in Ulcerative Colitis: A Proteome Analysis of Intestinal Biopsies” (Bennike et al., 2015 [1]), and “Proteome Analysis of Rheumatoid Arthritis Gut Mucosa” (Bennike et al., 2017 [2])...... been deposited to the ProteomeXchange Consortium via the PRIDE partner repository with the dataset identifiers PXD001608 for ulcerative colitis and control samples, and PXD003082 for rheumatoid arthritis samples....

  6. The SPS Target Station for CHORUS and NOMAD Neutrino Experiments

    CERN Document Server

    Péraire, S; Zazula, J M

    1996-01-01

    A new SPS target station, T9, has been constructed for the CHORUS and NOMAD neutrino experiments at CERN. The heart of the station is the target box : 11 beryllium rods are aligned in a cast aluminium box ; they are cooled by a closed circuit helium gas with adjusted flow to each rod. The box is motorised horizontally and vertically at both ends, to remotely optimise the secondary particle production by aligning the target with the incident proton beam. Radiation protection around the station is guaranteed by more than 100 tons of shielding material (iron, copper, marble). This presentation describes briefly the various components of the target station ; it emphasises particularly the thermal and mechanical calculations which define a safe maximum beam intensity on the beryllium rods. Over the first two years of successful operation, the station has received more than 2€1019 protons at 450 GeV/c, with intensity peaks of 2.8€1013 protons per machine cycle.

  7. Advances in target design and fabrication for experiments on NIF

    Directory of Open Access Journals (Sweden)

    Obrey K.

    2013-11-01

    Full Text Available The ability to build target platforms for National Ignition Facility (NIF is a key feature in LANL's (Los Alamos National Laboratory Target Fabrication Program. We recently built and manufactured the first LANL targets to be fielded on NIF in March 2011. Experiments on NIF require precision component manufacturing and accurate knowledge of the materials used in the targets. The characterization of foams and aerogels, the Be ignition capsule, and machining unique components are of main material focus. One important characterization metric the physics' have determined is that the knowledge of density gradients in foams is important. We are making strides in not only locating these density gradients in aerogels and foams as a result of how they are manufactured and machined but also quantifying the density within the foam using 3D confocal micro x-ray fluorescence (μXRF imaging and 3D x-ray computed tomography (CT imaging. In addition, collaborative efforts between General Atomics (GA and LANL in the characterization of the NIF Ignition beryllium capsule have shown that the copper in the capsule migrates radially from the capsule center.

  8. Feasibility study of an active target for the MEG experiment

    Energy Technology Data Exchange (ETDEWEB)

    Papa, A., E-mail: angela.papa@psi.ch [Paul Scherrer Institut PSI, CH-5232 Villigen (Switzerland); Cavoto, G. [INFN Sezione di Roma, P.le Aldo Moro, 2, 00185 Roma (Italy); Ripiccini, E. [INFN Sezione di Roma, P.le Aldo Moro, 2, 00185 Roma (Italy); Dipartimento di Fisica dell' Università degli studi di Roma, P.le Aldo Moro, 2, 00185 Roma (Italy)

    2014-03-01

    We consider the possibility to have an active target for the upgrade of the MEG experiment (MEG II). The active target should work as (1) a beam monitoring, to continuously measure the muon stopping rate and therefore provide a direct evaluation of the detector acceptance (or an absolute normalization of the stopped muon); and as (2) an auxiliary device for the spectrometer, to improve the determination of the muon decay vertex and consequently to achieve a better positron momentum and angular resolutions, detecting the positron from the muon decay. In this work we studied the feasibility of detecting minimum ionizing particle with a single layer of 250 μm fiber and the capability to discriminate between the signal induced by either a muon or a positron.

  9. New designs of LMJ targets for early ignition experiments

    International Nuclear Information System (INIS)

    Clerouin, C; Bonnefille, M; Dattolo, E; Fremerye, P; Galmiche, D; Gauthier, P; Giorla, J; Laffite, S; Liberatore, S; Loiseau, P; Malinie, G; Masse, L; Poggi, F; Seytor, P

    2008-01-01

    The LMJ experimental plans include the attempt of ignition and burn of an ICF capsule with 40 laser quads, delivering up to 1.4MJ and 380TW. New targets needing reduced laser energy with only a small decrease in robustness are then designed for this purpose. A first strategy is to use scaled-down cylindrical hohlraums and capsules, taking advantage of our better understanding of the problem, set on theoretical modelling, simulations and experiments. Another strategy is to work specifically on the coupling efficiency parameter, i.e. the ratio of the energy absorbed by the capsule to the laser energy, which is with parametric instabilities a crucial drawback of indirect drive. An alternative design is proposed, made up of the nominal 60 quads capsule, named A1040, in a rugby-shaped hohlraum. Robustness evaluations of these different targets are in progress

  10. New designs of LMJ targets for early ignition experiments

    Energy Technology Data Exchange (ETDEWEB)

    Clerouin, C; Bonnefille, M; Dattolo, E; Fremerye, P; Galmiche, D; Gauthier, P; Giorla, J; Laffite, S; Liberatore, S; Loiseau, P; Malinie, G; Masse, L; Poggi, F; Seytor, P [Commissariat a l' Energie Atomique, DAM-Ile de France, BP 12 91680 Bruyeres-le-Chatel (France)], E-mail: catherine.cherfils@cea.fr

    2008-05-15

    The LMJ experimental plans include the attempt of ignition and burn of an ICF capsule with 40 laser quads, delivering up to 1.4MJ and 380TW. New targets needing reduced laser energy with only a small decrease in robustness are then designed for this purpose. A first strategy is to use scaled-down cylindrical hohlraums and capsules, taking advantage of our better understanding of the problem, set on theoretical modelling, simulations and experiments. Another strategy is to work specifically on the coupling efficiency parameter, i.e. the ratio of the energy absorbed by the capsule to the laser energy, which is with parametric instabilities a crucial drawback of indirect drive. An alternative design is proposed, made up of the nominal 60 quads capsule, named A1040, in a rugby-shaped hohlraum. Robustness evaluations of these different targets are in progress.

  11. Feasibility study of an active target for the MEG experiment

    International Nuclear Information System (INIS)

    Papa, A.; Cavoto, G.; Ripiccini, E.

    2014-01-01

    We consider the possibility to have an active target for the upgrade of the MEG experiment (MEG II). The active target should work as (1) a beam monitoring, to continuously measure the muon stopping rate and therefore provide a direct evaluation of the detector acceptance (or an absolute normalization of the stopped muon); and as (2) an auxiliary device for the spectrometer, to improve the determination of the muon decay vertex and consequently to achieve a better positron momentum and angular resolutions, detecting the positron from the muon decay. In this work we studied the feasibility of detecting minimum ionizing particle with a single layer of 250 μm fiber and the capability to discriminate between the signal induced by either a muon or a positron

  12. Proteomic analysis of the action of the Mycobacterium ulcerans toxin mycolactone: targeting host cells cytoskeleton and collagen.

    Directory of Open Access Journals (Sweden)

    José B Gama

    2014-08-01

    Full Text Available Buruli ulcer (BU is a neglected tropical disease caused by Mycobacterium ulcerans. The tissue damage characteristic of BU lesions is known to be driven by the secretion of the potent lipidic exotoxin mycolactone. However, the molecular action of mycolactone on host cell biology mediating cytopathogenesis is not fully understood. Here we applied two-dimensional electrophoresis (2-DE to identify the mechanisms of mycolactone's cellular action in the L929 mouse fibroblast proteome. This revealed 20 changed spots corresponding to 18 proteins which were clustered mainly into cytoskeleton-related proteins (Dync1i2, Cfl1, Crmp2, Actg1, Stmn1 and collagen biosynthesis enzymes (Plod1, Plod3, P4ha1. In line with cytoskeleton conformational disarrangements that are observed by immunofluorescence, we found several regulators and constituents of both actin- and tubulin-cytoskeleton affected upon exposure to the toxin, providing a novel molecular basis for the effect of mycolactone. Consistent with these cytoskeleton-related alterations, accumulation of autophagosomes as well as an increased protein ubiquitination were observed in mycolactone-treated cells. In vivo analyses in a BU mouse model revealed mycolactone-dependent structural changes in collagen upon infection with M. ulcerans, associated with the reduction of dermal collagen content, which is in line with our proteomic finding of mycolactone-induced down-regulation of several collagen biosynthesis enzymes. Our results unveil the mechanisms of mycolactone-induced molecular cytopathogenesis on exposed host cells, with the toxin compromising cell structure and homeostasis by inducing cytoskeleton alterations, as well as disrupting tissue structure, by impairing the extracellular matrix biosynthesis.

  13. Proteomic analysis of the action of the Mycobacterium ulcerans toxin mycolactone: targeting host cells cytoskeleton and collagen.

    Science.gov (United States)

    Gama, José B; Ohlmeier, Steffen; Martins, Teresa G; Fraga, Alexandra G; Sampaio-Marques, Belém; Carvalho, Maria A; Proença, Fernanda; Silva, Manuel T; Pedrosa, Jorge; Ludovico, Paula

    2014-08-01

    Buruli ulcer (BU) is a neglected tropical disease caused by Mycobacterium ulcerans. The tissue damage characteristic of BU lesions is known to be driven by the secretion of the potent lipidic exotoxin mycolactone. However, the molecular action of mycolactone on host cell biology mediating cytopathogenesis is not fully understood. Here we applied two-dimensional electrophoresis (2-DE) to identify the mechanisms of mycolactone's cellular action in the L929 mouse fibroblast proteome. This revealed 20 changed spots corresponding to 18 proteins which were clustered mainly into cytoskeleton-related proteins (Dync1i2, Cfl1, Crmp2, Actg1, Stmn1) and collagen biosynthesis enzymes (Plod1, Plod3, P4ha1). In line with cytoskeleton conformational disarrangements that are observed by immunofluorescence, we found several regulators and constituents of both actin- and tubulin-cytoskeleton affected upon exposure to the toxin, providing a novel molecular basis for the effect of mycolactone. Consistent with these cytoskeleton-related alterations, accumulation of autophagosomes as well as an increased protein ubiquitination were observed in mycolactone-treated cells. In vivo analyses in a BU mouse model revealed mycolactone-dependent structural changes in collagen upon infection with M. ulcerans, associated with the reduction of dermal collagen content, which is in line with our proteomic finding of mycolactone-induced down-regulation of several collagen biosynthesis enzymes. Our results unveil the mechanisms of mycolactone-induced molecular cytopathogenesis on exposed host cells, with the toxin compromising cell structure and homeostasis by inducing cytoskeleton alterations, as well as disrupting tissue structure, by impairing the extracellular matrix biosynthesis.

  14. Studies on the target detector of the LAND experiment

    International Nuclear Information System (INIS)

    Zinser, M.

    1991-09-01

    In the framework of this diploma thesis the target detector of the LAND experiment was for the first time taken into operation. The target detector consists of 48 BaF 2 crystals and 36 plastic scintillators. The BaF 2 detectors shall be mainly applied to the measurements of Γ quanta from giant resonance excitations and transitions in exotic nuclei. The plastic scintillators serve for the determination of the multiplicity of the charged particles emitted in a reaction. The electronics of the target detector were for the first experiment of the LAND collaboration on the electromagnetic excitation in peripheral heavy ion reactions at near-relativistic energies together constructed and tested. In the following for the BaF 2 crystals calibration measurements with two γ sources and for the plastic scintillators with a β preparate were performed. The evaluation of the measurements was performed on a VAX station of the Mainz University, on which a by the LAND collaboration modified version of the analysis program PAW was installed. The analysis of the plastic scintillators yields a bad energy resolution of at least 0.6. For the BaF 2 detectors PAW was extended by a comand, which allows a semi-automatic performation of the calibration. The results obtained by this procedure are consistent with calibrations, which were performed independently on this in the collaboration. By the new routine it is possible to perform the energy calibration of the BaF 2 crystals fastly and efficiently. The resolution of the BaF 2 detectors lies around 10%. By this experiments on the giant-resonance excitation and first studies on γ transitions with exotic nuclei are performable. (orig./HSI) [de

  15. Tensor polarized deuteron targets for intermediate energy physics experiments

    International Nuclear Information System (INIS)

    Meyer, W.; Schilling, E.

    1985-03-01

    At intermediate energies measurements from a tensor polarized deuteron target are being prepared for the following reactions: the photodisintegration of the deuteron, the elastic pion-deuteron scattering and the elastic electron-deuteron scattering. The experimental situation of the polarization experiments for these reactions is briefly discussed in section 2. In section 3 the definitions of the deuteron polarization and the possibilities to determine the vector and tensor polarization are given. Present tensor polarization values and further improvements in this field are reported in section 4. (orig.)

  16. Proteomics in pulmonary research: selected methodical aspects

    Directory of Open Access Journals (Sweden)

    Martin Petrek

    2007-10-01

    Full Text Available Recent years witness rapid expansion of applications of proteomics to clinical research including non-malignant lung disorders. These developments bring along the need for standardisation of proteomic experiments. This paper briefly reviews basic methodical aspects of appliedproteomic studies using SELDI-TOF mass spectrometry platform as example but also emphasizes general aspects of quality assurance in proteomics. Key-words: lung proteome, quality assurance, SELDI-TOF MS

  17. PLANS FOR WARM DENSE MATTER EXPERIMENTS AND IFE TARGET EXPERIMENTS ON NDCX-II

    International Nuclear Information System (INIS)

    Waldron, W.L.; Barnard, J.J.; Bieniosek, F.M.; Friedman, A.; Henestroza, E.; Leitner, M.; Logan, B.G.; Ni, P.A.; Roy, P.K.; Seidl, P.A.; Sharp, W.M.

    2008-01-01

    The Heavy Ion Fusion Science Virtual National Laboratory (HIFS-VNL) is currently developing design concepts for NDCX-II, the second phase of the Neutralized Drift Compression Experiment, which will use ion beams to explore Warm Dense Matter (WDM) and Inertial Fusion Energy (IFE) target hydrodynamics. The ion induction accelerator will consist of a new short pulse injector and induction cells from the decommissioned Advanced Test Accelerator (ATA) at Lawrence Livermore National Laboratory (LLNL). To fit within an existing building and to meet the energy and temporal requirements of various target experiments, an aggressive beam compression and acceleration schedule is planned. WDM physics and ion-driven direct drive hydrodynamics will initially be explored with 30 nC of lithium ions in experiments involving ion deposition, ablation, acceleration and stability of planar targets. Other ion sources which may deliver higher charge per bunch will be explored. A test stand has been built at Lawrence Berkeley National Laboratory (LBNL) to test refurbished ATA induction cells and pulsed power hardware for voltage holding and ability to produce various compression and acceleration waveforms. Another test stand is being used to develop and characterize lithium-doped aluminosilicate ion sources. The first experiments will include heating metallic targets to 10,000 K and hydrodynamics studies with cryogenic hydrogen targets

  18. A proteomic screen reveals the mitochondrial outer membrane protein Mdm34p as an essential target of the F-box protein Mdm30p.

    Science.gov (United States)

    Ota, Kazuhisa; Kito, Keiji; Okada, Satoshi; Ito, Takashi

    2008-10-01

    Ubiquitination plays various critical roles in eukaryotic cellular regulation and is mediated by a cascade of enzymes including ubiquitin protein ligase (E3). The Skp1-Cullin-F-box protein complex comprises the largest E3 family, in each member of which a unique F-box protein binds its targets to define substrate specificity. Although genome sequencing uncovers a growing number of F-box proteins, most of them have remained as "orphans" because of the difficulties in identification of their substrates. To address this issue, we tested a quantitative proteomic approach by combining the stable isotope labeling by amino acids in cell culture (SILAC), parallel affinity purification (PAP) that we had developed for efficient enrichment of ubiquitinated proteins, and mass spectrometry (MS). We applied this SILAC-PAP-MS approach to compare ubiquitinated proteins between yeast cells with and without over-expressed Mdm30p, an F-box protein implicated in mitochondrial morphology. Consequently, we identified the mitochondrial outer membrane protein Mdm34p as a target of Mdm30p. Furthermore, we found that mitochondrial defects induced by deletion of MDM30 are not only recapitulated by a mutant Mdm34p defective in interaction with Mdm30p but alleviated by ubiquitination-mimicking forms of Mdm34p. These results indicate that Mdm34p is a physiologically important target of Mdm30p.

  19. Target experiments with high-power proton beams

    Energy Technology Data Exchange (ETDEWEB)

    Baumung, K; Bluhm, H; Hoppe, P; Rusch, D; Singer, J; Stoltz, O [Forschungszentrum Karlsruhe (Germany); Kanel, G I; Razorenov, S V; Utkin, A V [Russian Academy of Sciences, Chernogolovka (Russian Federation). Inst. of Chemical Physics

    1997-12-31

    At the Karlsruhe Light Ion Facility KALE a pulsed high-power proton beam (50 ns, 0.15 TW/cm{sup 2}, 8 mm fwhm focus diameter, 1.7 MeV peak proton energy) is used to generate short, intense pressure pulses or to ablatively accelerate targets 10-100 {mu}m thick to velocities > 10 km/s. The velocity history of the rear target surface is recorded by line-imaging laser Doppler velocimetry with high spatial ({>=} 10 {mu}m) and temporal ({>=} 200 ps) resolution, and provides information on proton beam parameters, and on the state of the matter at high energy densities and intense loading. Utilizing the bell-shaped power density profile the authors demonstrated a new straightforward method for measuring the shock pressure that leads to material melting in the rarefaction wave. For the first time, the dynamic tensile strength was measured across a crystal grain boundary, and using targets with a 1D periodic structure, the growth rate of a Rayleigh Taylor instability could be measured for the first time in direct drive experiments with an ion beam. (author). 8 figs., 15 refs.

  20. Baseball II-T, a new target plasma startup experiment

    International Nuclear Information System (INIS)

    Chargin, A.; Denhoy, B.; Frank, A.; Thomas, S.

    1975-01-01

    A brief description is given of modifications and additions to the existing Baseball II experiment. These changes will make it possible to study target plasma buildup in a steady-state magnetic field. This experiment, now called Baseball II-T + will use a pellet generator to deliver ammonia pellets into the center of the magnetic mirror field where they will be heated with a 300-J, 50-ns, CO 2 laser. The plasma created by this method will have a density of approximately 10 13 cm -3 and a temperature of about 1 keV. This target plasma will be used for neutral beam injection startup studies with a 50-A, 20-keV neutral beam. Later, the beam power will be increased to study buildup. With ion injection energies of up to 50 keV, it may be possible to achieve etatau as high as 10 12 cm -3 s. The new components necessary to achieve these goals are described

  1. Evolution of Clinical Proteomics and its Role in Medicine | Office of Cancer Clinical Proteomics Research

    Science.gov (United States)

    NCI's Office of Cancer Clinical Proteomics Research authored a review of the current state of clinical proteomics in the peer-reviewed Journal of Proteome Research. The review highlights outcomes from the CPTC program and also provides a thorough overview of the different technologies that have pushed the field forward. Additionally, the review provides a vision for moving the field forward through linking advances in genomic and proteomic analysis to develop new, molecularly targeted interventions.

  2. Proteomic Profiling of Radiation-Induced Skin Fibrosis in Rats: Targeting the Ubiquitin-Proteasome System

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Wenjie [School of Radiation Medicine and Protection and Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions, Soochow University, Suzhou (China); Cyrus Tang Hematology Center, Soochow University, Suzhou (China); Luo, Judong [Department of Radiotherapy, Changzhou Tumor Hospital, Soochow University, Changzhou (China); Sheng, Wenjiong; Xue, Jiao; Li, Ming [School of Radiation Medicine and Protection and Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions, Soochow University, Suzhou (China); Ji, Jiang [Department of Dermatology, the Second Affiliated Hospital of Soochow University, Suzhou (China); Liu, Pengfei [Department of Gastroenterology, the Affiliated Jiangyin Hospital of Southeast University, Jiangyin (China); Zhang, Xueguang [Institute of Medical Biotechnology and Jiangsu Stem Cell Key Laboratory, Medical College of Soochow University, Suzhou (China); Cao, Jianping [School of Radiation Medicine and Protection and Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions, Soochow University, Suzhou (China); Zhang, Shuyu, E-mail: zhang.shuyu@hotmail.com [School of Radiation Medicine and Protection and Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions, Soochow University, Suzhou (China); Cyrus Tang Hematology Center, Soochow University, Suzhou (China)

    2016-06-01

    Purpose: To investigate the molecular changes underlying the pathogenesis of radiation-induced skin fibrosis. Methods and Materials: Rat skin was irradiated to 30 or 45 Gy with an electron beam. Protein expression in fibrotic rat skin and adjacent normal tissues was quantified by label-free protein quantitation. Human skin cells HaCaT and WS-1 were treated by x-ray irradiation, and the proteasome activity was determined with a fluorescent probe. The effect of proteasome inhibitors on Transforming growth factor Beta (TGF-B) signaling was measured by Western blot and immunofluorescence. The efficacy of bortezomib in wound healing of rat skin was assessed by the skin injury scale. Results: We found that irradiation induced epidermal and dermal hyperplasia in rat and human skin. One hundred ninety-six preferentially expressed and 80 unique proteins in the irradiated fibrotic skin were identified. Through bioinformatic analysis, the ubiquitin-proteasome pathway showed a significant fold change and was investigated in greater detail. In vitro experiments demonstrated that irradiation resulted in a decline in the activity of the proteasome in human skin cells. The proteasome inhibitor bortezomib suppressed profibrotic TGF-β downstream signaling but not TGF-β secretion stimulated by irradiation in HaCaT and WS-1 cells. Moreover, bortezomib ameliorated radiation-induced skin injury and attenuated epidermal hyperplasia. Conclusion: Our findings illustrate the molecular changes during radiation-induced skin fibrosis and suggest that targeting the ubiquitin-proteasome system would be an effective countermeasure.

  3. Proteomics approaches for identification of tumor relevant protein targets in pulmonary squamous cell carcinoma by 2D-DIGE-MS.

    Directory of Open Access Journals (Sweden)

    Hao Lihong

    Full Text Available Potential markers for progression of pulmonary squamous cell carcinoma (SCC were identified by examining samples of lung SCC and adjacent normal tissues using a combination of fluorescence two-dimensional difference gel electrophoresis (2D-DIGE, matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF-MS, and electrospray ionization quadrupole-time of flight mass spectrometry (ESI-Q-TOF. The PANTHER System was used for gel image based quantification and statistical analysis. An analysis of proteomic data revealed that 323 protein spots showed significantly different levels of expression (P ≤ 0.05 in lung SCC tissue compared to expression in normal lung tissue. A further analysis of these protein spots by MALDI-TOF-MS identified 81 different proteins. A systems biology approach was used to map these proteins to major pathways involved in numerous cellular processes, including localization, transport, cellular component organization, apoptosis, and reproduction. Additionally, the expression of several proteins in lung SCC and normal tissues was examined using immunohistochemistry and western blot. The functions of individual proteins are being further investigated and validated, and the results might provide new insights into the mechanism of lung SCC progression, potentially leading to the design of novel diagnostic and therapeutic strategies.

  4. The first target experiments on the National Ignition Facility

    International Nuclear Information System (INIS)

    Landen, O.L.; Glenzer, S.H.; Froula, D.H.; Dewald, E.L.; Suter, L.J.; Schneider, M.B.; Hinkel, D.E.; Fernandez, J.C.; Kline, J.L.; Goldman, S.R.; Braun, D.G.; Celliers, P.M.; Moon, S.J.; Robey, H.S.; Lanier, N.E.; Glendinning, S.G.; Blue, B.E.; Wilde, B.H.; Jones, O.S.; Schein, J.; Divol, L.; Kalantar, D.H.; Campbell, K.M.; Holder, J.P.; McDonald, J.W.; Niemann, C.; Mackinnon, A.J.; Collins, G.W.; Bradley, D.K.; Eggert, J.H.; Hicks, D.G.; Gregori, G.; Kirkwood, R.K.; Young, B.K.; Foster, J.M.; Hansen, J.F.; Perry, T.S.; Munro, D.H.; Baldis, H.A.; Grim, G.P.; Heeter, R.F.; Hegelich, M.B.; Montgomery, D.S.; Rochau, G.A.; Olson, R.E.; Turner, R.E.; Workman, J.B.; Berger, R.L.; Cohen, B.I.; Kruer, W.L.; Langdon, A.B.; Langer, S.H.; Meezan, N.B.; Rose, H.A.; Still, C.H.; Williams, E.A.; Dodd, E.A.; Edwards, M.J.; Monteil, M.C.; Stevenson, R.M.; Thomas, B.R.; Coker, R.F.; Magelssen, G.R.; Rosen, P.A.; Stry, P.E.; Woods, D.; Weber, S.V.; Young, P.E.; Alvarez, S.; Armstrong, G.; Bahr, R.; Bourgade, G.L.; Bower, D.; Celeste, J.; Chrisp, M.; Compton, S.; Cox, J.; Constantin, C.; Costa, R.; Duncan, J.; Ellis, A.; Emig, J.; Gautier, C.; Greenwood, A.; Griffith, R.; Holdner, F.; Holtmeier, G.; Hargrove, D.; James, T.; Kamperschroer, J.; Kimbrough, J.; Landon, M.; Lee, F.D.; Malone, R.; May, M.; Montelongo, S.; Moody, J.; Ng, E.; Nikitin, A.; Pellinen, D.; Piston, K.; Poole, M.; Rekow, V.; Rhodes, M.; Shepherd, R.; Shiromizu, S.; Voloshin, D.; Warrick, A.; Watts, P.; Weber, F.; Young, P.; Arnold, P.

    2007-01-01

    A first set of shock timing, laser-plasma interaction, hohlraum energetics and hydrodynamic experiments have been performed using the first 4 beams of the National Ignition Facility (NIF), in support of indirect drive Inertial Confinement Fusion (ICF) and High Energy Density Physics (HEDP). In parallel, a robust set of optical and X-ray spectrometers, interferometer, calorimeters and imagers have been activated. The experiments have been undertaken with laser powers and energies of up to 8 TW and 17 kJ in flattop and shaped 1-9 ns pulses focused with various beam smoothing options. The experiments have demonstrated excellent agreement between measured and predicted laser-target coupling in foils and hohlraums, even when extended to a longer pulse regime unattainable at previous laser facilities, validated the predicted effects of beam smoothing on intense laser beam propagation in long scale-length plasmas and begun to test 3-dimensional codes by extending the study of laser driven hydrodynamic jets to 3-dimensional geometries. (authors)

  5. The first target experiments on the National Ignition Facility

    Energy Technology Data Exchange (ETDEWEB)

    Landen, O.L.; Glenzer, S.H.; Froula, D.H.; Dewald, E.L.; Suter, L.J.; Schneider, M.B.; Hinkel, D.E.; Fernandez, J.C.; Kline, J.L.; Goldman, S.R.; Braun, D.G.; Celliers, P.M.; Moon, S.J.; Robey, H.S.; Lanier, N.E.; Glendinning, S.G.; Blue, B.E.; Wilde, B.H.; Jones, O.S.; Schein, J.; Divol, L.; Kalantar, D.H.; Campbell, K.M.; Holder, J.P.; McDonald, J.W.; Niemann, C.; Mackinnon, A.J.; Collins, G.W.; Bradley, D.K.; Eggert, J.H.; Hicks, D.G.; Gregori, G.; Kirkwood, R.K.; Young, B.K.; Foster, J.M.; Hansen, J.F.; Perry, T.S.; Munro, D.H.; Baldis, H.A.; Grim, G.P.; Heeter, R.F.; Hegelich, M.B.; Montgomery, D.S.; Rochau, G.A.; Olson, R.E.; Turner, R.E.; Workman, J.B.; Berger, R.L.; Cohen, B.I.; Kruer, W.L.; Langdon, A.B.; Langer, S.H.; Meezan, N.B.; Rose, H.A.; Still, C.H.; Williams, E.A.; Dodd, E.A.; Edwards, M.J.; Monteil, M.C.; Stevenson, R.M.; Thomas, B.R.; Coker, R.F.; Magelssen, G.R.; Rosen, P.A.; Stry, P.E.; Woods, D.; Weber, S.V.; Young, P.E.; Alvarez, S.; Armstrong, G.; Bahr, R.; Bourgade, G.L.; Bower, D.; Celeste, J.; Chrisp, M.; Compton, S.; Cox, J.; Constantin, C.; Costa, R.; Duncan, J.; Ellis, A.; Emig, J.; Gautier, C.; Greenwood, A.; Griffith, R.; Holdner, F.; Holtmeier, G.; Hargrove, D.; James, T.; Kamperschroer, J.; Kimbrough, J.; Landon, M.; Lee, F.D.; Malone, R.; May, M.; Montelongo, S.; Moody, J.; Ng, E.; Nikitin, A.; Pellinen, D.; Piston, K.; Poole, M.; Rekow, V.; Rhodes, M.; Shepherd, R.; Shiromizu, S.; Voloshin, D.; Warrick, A.; Watts, P.; Weber, F.; Young, P.; Arnold, P

    2007-08-15

    A first set of shock timing, laser-plasma interaction, hohlraum energetics and hydrodynamic experiments have been performed using the first 4 beams of the National Ignition Facility (NIF), in support of indirect drive Inertial Confinement Fusion (ICF) and High Energy Density Physics (HEDP). In parallel, a robust set of optical and X-ray spectrometers, interferometer, calorimeters and imagers have been activated. The experiments have been undertaken with laser powers and energies of up to 8 TW and 17 kJ in flattop and shaped 1-9 ns pulses focused with various beam smoothing options. The experiments have demonstrated excellent agreement between measured and predicted laser-target coupling in foils and hohlraums, even when extended to a longer pulse regime unattainable at previous laser facilities, validated the predicted effects of beam smoothing on intense laser beam propagation in long scale-length plasmas and begun to test 3-dimensional codes by extending the study of laser driven hydrodynamic jets to 3-dimensional geometries. (authors)

  6. Complete fabrication of target experimental chamber and implement initial target diagnostics to be used for the first target experiments in NDCX-1

    International Nuclear Information System (INIS)

    Bieniosek, F.M.; Bieniosek, F.M.; Dickinson, M.R.; Henestroza, E.; Katayanagi, T.; Jung, J.Y.; Lee, C.W.; Leitner, M.; Ni, P.; Roy, P.; Seidl, P.; Waldron, W.; Welch, D.

    2008-01-01

    The Heavy Ion Fusion Science Virtual National Laboratory (HIFS-VNL) has completed the fabrication of a new experimental target chamber facility for future Warm Dense Matter (WDM) experiments, and implemented initial target diagnostics to be used for the first target experiments in NDCX-1. The target chamber has been installed on the NDCX-I beamline. This achievement provides to the HIFS-VNL unique and state-of-the-art experimental capabilities in preparation for the planned target heating experiments using intense heavy ion beams

  7. Cooling System for the Merit High-Power Target Experiment

    CERN Document Server

    Haug, F; Silva, P; Pezzeti, M; Pavlov, O; Pirotte, O; Metselaar, J; Efthymiopoulos, I; Fabich, A; Lettry, J; Kirk, H G; McDonald, K T; Titus, P; Bennett, J R J

    2010-01-01

    MERIT is a proof-of-principle experiment of a target station suitable as source for future muon colliders or neutrino factories. When installed at the CERN (European Organization for Nuclear Research) PS (Proton Synchrotron)complex fast-extracted high-intensity proton beams intercepted a free mercury jet inside a normal-conducting, pulsed 15-T capture solenoid magnet cooled with liquid nitrogen. Up to 25 MJ of Joule heat was dissipated in the magnet during a pulse. The fully automated, remotely controlled cryogenic system of novel design permitted the transfer of nitrogen by the sole means of differential pressures inside the vessels. This fast cycling system permitted several hundred tests in less than three weeks during the 2007 data taking campaign.

  8. 'Targeting' sedation: the lived experience of the intensive care nurse.

    Science.gov (United States)

    Everingham, Kirsty; Fawcett, Tonks; Walsh, Tim

    2014-03-01

    To discuss the findings from a phenomenological study that provides insights into the intensive care nurses' 'world' following changes in the sedation management of patients in an intensive care unit. Intensive care sedation practices have undergone significant changes. Patients, where possible, are now managed on lighter levels of sedation, often achieved through the performance of sedation holds (SHs). The performance of SHs is normally carried out by the bedside nurse but compliance is reported to be poor. There has been little exploration of the nurses' experiences of these changes and the implications of SHs and subsequent wakefulness on their delivery of care. Following ethical approval, 16 intensive care nurses, experienced and inexperienced, from within a general intensive care unit. A Heideggerian phenomenological approach was used. Data collection consisted of interviews guided by an aide memoir and a framework adapted from Van Manen informed the analysis. The findings reveal new insights into the world of the intensive care nurse in the light of the changes to sedation management. They demonstrate that there have been unforeseen outcomes from well-intentioned initiatives to improve the quality of patients' care. There were implications from the changes introduced for the nurses care delivery. The main themes that emerged were 'working priorities' and 'unintended consequences', in turn revealing embedded tensions between evidence-based targets and holistic care. Intensive care nurses find that the current approach to the changes in sedation management can threaten their professional obligation and personal desire to provide holistic care. The 'targeted' approach by healthcare organisations is perceived to militate against the patient-centred care they want to deliver. Sedation management is complex and needs further consideration particularly the potential constraints 'target-led' care has on nursing practice. © 2013 Blackwell Publishing Ltd.

  9. Cylindrical target Li-beam-driven hohlraum experiments

    International Nuclear Information System (INIS)

    Derzon, M.S.; Aubert, J.; Chandler, G.A.

    1998-06-01

    The authors performed a series of experiments on the Particle Beam Fusion Accelerator II (PBFA II) in May, 1994, and obtained a brightness temperature of 61 ± 2 eV for an ion-beam heated hohlraum. The hohlraum was a 4-mm-diameter, right-circular cylinder with a 1.5-mm-thick gold wall, a low-density CH foam fill, and a 1.5- or 3-mm-diameter diagnostic aperture in the top. The nominal parameters of the radially-incident PBFA II Li ion beam were 9 MeV peak energy (∼10 MeV at the gas cell) at the target at a peak power of 2.5 ± 0.3 TW/cm 2 and a 15 ns pulse width. Azimuthal variations in intensity of a factor of 3, with respect to the mean, were observed. Nonuniformities in thermal x-ray emission across the area of the diagnostic hole were also observed. Time-dependent hole-closure velocities were measured: the time-averaged velocity of ∼2 cm/micros is in good agreement with sound speed estimates. Unfolded x-ray spectra and brightness temperatures as a function of time are reported and compared to simulations. Hole closure corrections are discussed with comparisons between XRD and bolometer measurements. Temperature scaling with power on target is also presented

  10. Proposed Fermilab fixed target experiment: Kaons at the Tevatron

    International Nuclear Information System (INIS)

    1993-12-01

    The US Department of Energy (DOE) has prepared an Environmental Assessment (EA), DOE/EA-0898, evaluating the impacts associated with the proposed fixed target experiment at the Fermi National Accelerator Laboratory (Femilab) in Batavia, Illinois, known as Kaons at the Tevatron (KTeV). The proposed KTeV project includes reconfiguration of an existing target station, enhancement of an existing beam transport system connected to existing utility facilities, and construction of a new experimental detector hall area. The study of the K meson, a type of subatomic particle, has been going on at Fermilab for 20 years. The proposed KTEV project advances the search for the origins of a violation of a fundamental symmetry of nature called charge parity (CP) violation. Based on the analysis in the EA, the DOE has determined that the proposed action does not constitute a major Federal action significantly affecting the quality of the human environment, within the meaning of the National Environmental Policy Act (NEPA) of 1969. Therefore, the preparation of an Environmental Impact Statement is not required

  11. Application of targeted quantitative proteomics analysis in human cerebrospinal fluid using a liquid chromatography matrix-assisted laser desorption/ionization time-of-flight tandem mass spectrometer (LC MALDI TOF/TOF) platform.

    Science.gov (United States)

    Pan, Sheng; Rush, John; Peskind, Elaine R; Galasko, Douglas; Chung, Kathryn; Quinn, Joseph; Jankovic, Joseph; Leverenz, James B; Zabetian, Cyrus; Pan, Catherine; Wang, Yan; Oh, Jung Hun; Gao, Jean; Zhang, Jianpeng; Montine, Thomas; Zhang, Jing

    2008-02-01

    Targeted quantitative proteomics by mass spectrometry aims to selectively detect one or a panel of peptides/proteins in a complex sample and is particularly appealing for novel biomarker verification/validation because it does not require specific antibodies. Here, we demonstrated the application of targeted quantitative proteomics in searching, identifying, and quantifying selected peptides in human cerebrospinal spinal fluid (CSF) using a matrix-assisted laser desorption/ionization time-of-flight tandem mass spectrometer (MALDI TOF/TOF)-based platform. The approach involved two major components: the use of isotopic-labeled synthetic peptides as references for targeted identification and quantification and a highly selective mass spectrometric analysis based on the unique characteristics of the MALDI instrument. The platform provides high confidence for targeted peptide detection in a complex system and can potentially be developed into a high-throughput system. Using the liquid chromatography (LC) MALDI TOF/TOF platform and the complementary identification strategy, we were able to selectively identify and quantify a panel of targeted peptides in the whole proteome of CSF without prior depletion of abundant proteins. The effectiveness and robustness of the approach associated with different sample complexity, sample preparation strategies, as well as mass spectrometric quantification were evaluated. Other issues related to chromatography separation and the feasibility for high-throughput analysis were also discussed. Finally, we applied targeted quantitative proteomics to analyze a subset of previously identified candidate markers in CSF samples of patients with Parkinson's disease (PD) at different stages and Alzheimer's disease (AD) along with normal controls.

  12. Chemical proteomics approach reveals the direct targets and the heme-dependent activation mechanism of artemisinin in Plasmodium falciparum using an activity-based artemisinin probe

    Directory of Open Access Journals (Sweden)

    Jigang Wang

    2016-04-01

    Full Text Available Artemisinin and its analogues are currently the most effective anti-malarial drugs. The activation of artemisinin requires the cleavage of the endoperoxide bridge in the presence of iron sources. Once activated, artemisinins attack macromolecules through alkylation and propagate a series of damages, leading to parasite death. Even though several parasite proteins have been reported as artemisinin targets, the exact mechanism of action (MOA of artemisinin is still controversial and its high potency and specificity against the malaria parasite could not be fully accounted for. Recently, we have developed an unbiased chemical proteomics approach to directly probe the MOA of artemisinin in P. falciparum. We synthesized an activity-based artemisinin probe with an alkyne tag, which can be coupled with biotin through click chemistry. This enabled selective purification and identification of 124 protein targets of artemisinin. Many of these targets are critical for the parasite survival. In vitro assays confirmed the specific artemisinin binding and inhibition of selected targets. We thus postulated that artemisinin kills the parasite through disrupting its biochemical landscape. In addition, we showed that artemisinin activation requires heme, rather than free ferrous iron, by monitoring the extent of protein binding using a fluorescent dye coupled with the alkyne-tagged artemisinin. The extremely high level of heme released from the hemoglobin digestion by the parasite makes artemisinin exceptionally potent against late-stage parasites (trophozoite and schizont stages compared to parasites at early ring stage, which have low level of heme, possibly derived from endogenous synthesis. Such a unique activation mechanism also confers artemisinin with extremely high specificity against the parasites, while the healthy red blood cells are unaffected. Our results provide a sound explanation of the MOA of artemisinin and its specificity against malaria

  13. The Drosophila melanogaster PeptideAtlas facilitates the use of peptide data for improved fly proteomics and genome annotation

    Directory of Open Access Journals (Sweden)

    King Nichole L

    2009-02-01

    Full Text Available Abstract Background Crucial foundations of any quantitative systems biology experiment are correct genome and proteome annotations. Protein databases compiled from high quality empirical protein identifications that are in turn based on correct gene models increase the correctness, sensitivity, and quantitative accuracy of systems biology genome-scale experiments. Results In this manuscript, we present the Drosophila melanogaster PeptideAtlas, a fly proteomics and genomics resource of unsurpassed depth. Based on peptide mass spectrometry data collected in our laboratory the portal http://www.drosophila-peptideatlas.org allows querying fly protein data observed with respect to gene model confirmation and splice site verification as well as for the identification of proteotypic peptides suited for targeted proteomics studies. Additionally, the database provides consensus mass spectra for observed peptides along with qualitative and quantitative information about the number of observations of a particular peptide and the sample(s in which it was observed. Conclusion PeptideAtlas is an open access database for the Drosophila community that has several features and applications that support (1 reduction of the complexity inherently associated with performing targeted proteomic studies, (2 designing and accelerating shotgun proteomics experiments, (3 confirming or questioning gene models, and (4 adjusting gene models such that they are in line with observed Drosophila peptides. While the database consists of proteomic data it is not required that the user is a proteomics expert.

  14. Protein interaction networks by proteome peptide scanning.

    Directory of Open Access Journals (Sweden)

    Christiane Landgraf

    2004-01-01

    Full Text Available A substantial proportion of protein interactions relies on small domains binding to short peptides in the partner proteins. Many of these interactions are relatively low affinity and transient, and they impact on signal transduction. However, neither the number of potential interactions mediated by each domain nor the degree of promiscuity at a whole proteome level has been investigated. We have used a combination of phage display and SPOT synthesis to discover all the peptides in the yeast proteome that have the potential to bind to eight SH3 domains. We first identified the peptides that match a relaxed consensus, as deduced from peptides selected by phage display experiments. Next, we synthesized all the matching peptides at high density on a cellulose membrane, and we probed them directly with the SH3 domains. The domains that we have studied were grouped by this approach into five classes with partially overlapping specificity. Within the classes, however, the domains display a high promiscuity and bind to a large number of common targets with comparable affinity. We estimate that the yeast proteome contains as few as six peptides that bind to the Abp1 SH3 domain with a dissociation constant lower than 100 microM, while it contains as many as 50-80 peptides with corresponding affinity for the SH3 domain of Yfr024c. All the targets of the Abp1 SH3 domain, identified by this approach, bind to the native protein in vivo, as shown by coimmunoprecipitation experiments. Finally, we demonstrate that this strategy can be extended to the analysis of the entire human proteome. We have developed an approach, named WISE (whole interactome scanning experiment, that permits rapid and reliable identification of the partners of any peptide recognition module by peptide scanning of a proteome. Since the SPOT synthesis approach is semiquantitative and provides an approximation of the dissociation constants of the several thousands of interactions that are

  15. Development of target capsules for muon catalyzed fusion experiments

    International Nuclear Information System (INIS)

    Watts, K.D.; Jones, S.E.; Caffrey, A.J.

    1983-01-01

    A series of Muon Catalyzed Fusion experiments has been conducted at the Los Alamos Meson Physics Facility to determine how many fusion reactions one muon would catalyze under various temperature, pressure, contamination, and tritium concentration conditions. Target capsules to contain deuterium and tritium at elevated temperatures and pressures were engineered for a maximum temperature of 540 K (512 0 F) and a maximum pressure of 103 MPa (15,000 psig). Experimental data collected with these capsules indicated that the number of fusion reactions per muon continued to increase with temperature up to the 540-K design limit. Theory had indicated that the reaction rate should peak at approximately 540 K, but this was not confirmed during the experiments. A second generation of capsules which have a maximum design temperature of 800 K (980 0 F) and a maximum design pressure of 103 MPa (15,000 psig) has now been engineered. These new capsules will be used to further study the muon catalysis rate versus deuterium-tritium mixture temperature

  16. Cutting edge proteomics

    DEFF Research Database (Denmark)

    Bunkenborg, Jakob; Espadas, Guadalupe; Molina, Henrik

    2013-01-01

    Tryptic digestion is an important component of most proteomics experiments, and trypsin is available from many sources with a cost that varies by more than 1000-fold. This high-mass-accuracy LC-MS study benchmarks six commercially available trypsins with respect to autolytic species and sequence ...

  17. Proteomics dataset

    DEFF Research Database (Denmark)

    Bennike, Tue Bjerg; Carlsen, Thomas Gelsing; Ellingsen, Torkell

    2017-01-01

    patients (Morgan et al., 2012; Abraham and Medzhitov, 2011; Bennike, 2014) [8–10. Therefore, we characterized the proteome of colon mucosa biopsies from 10 inflammatory bowel disease ulcerative colitis (UC) patients, 11 gastrointestinal healthy rheumatoid arthritis (RA) patients, and 10 controls. We...... been deposited to the ProteomeXchange Consortium via the PRIDE partner repository with the dataset identifiers PXD001608 for ulcerative colitis and control samples, and PXD003082 for rheumatoid arthritis samples....

  18. Genomics and proteomics: Applications in autoimmune diseases

    Directory of Open Access Journals (Sweden)

    Wolfgang Hueber

    2009-08-01

    Full Text Available Wolfgang Hueber1,2,3, William H Robinson1,21VA Palo Alto Health Care System, Palo Alto, CA, USA; 2Division of Immunology and Rheumatology, Stanford University School of Medicine, Stanford, CA, USA; 3Novartis Institutes of Biomedical Research, Novartis, Basle, SwitzerlandAbstract: Tremendous progress has been made over the past decade in the development and refinement of genomic and proteomic technologies for the identification of novel drug targets and molecular signatures associated with clinically important disease states, disease subsets, or differential responses to therapies. The rapid progress in high-throughput technologies has been preceded and paralleled by the elucidation of cytokine networks, followed by the stepwise clinical development of pathway-specific biological therapies that revolutionized the treatment of autoimmune diseases. Together, these advances provide opportunities for a long-anticipated personalized medicine approach to the treatment of autoimmune disease. The ever-increasing numbers of novel, innovative therapies will need to be harnessed wisely to achieve optimal long-term outcomes in as many patients as possible while complying with the demands of health authorities and health care providers for evidence-based, economically sound prescription of these expensive drugs. Genomic and proteomic profiling of patients with autoimmune diseases holds great promise in two major clinical areas: (1 rapid identification of new targets for the development of innovative therapies and (2 identification of patients who will experience optimal benefit and minimal risk from a specific (targeted therapy. In this review, we attempt to capture important recent developments in the application of genomic and proteomic technologies to translational research by discussing informative examples covering a diversity of autoimmune diseases.Keywords: proteomics, genomics, autoimmune diseases, antigen microarrays, 2-Dih, rheumatoid arthritis

  19. Proteome-wide analysis of SUMO2 targets in response to pathological DNA replication stress in human cells

    DEFF Research Database (Denmark)

    Bursomanno, Sara; Beli, Petra; Khan, Asif M

    2015-01-01

    SUMOylation is a form of post-translational modification involving covalent attachment of SUMO (Small Ubiquitin-like Modifier) polypeptides to specific lysine residues in the target protein. In human cells, there are four SUMO proteins, SUMO1-4, with SUMO2 and SUMO3 forming a closely related subf......, and that excessive replication stress is a hallmark of pre-neoplastic and tumor cells, our characterization of SUMO2 targets during a perturbed S-phase should provide a valuable resource for future functional studies in the fields of DNA metabolism and cancer biology....

  20. Target focusing configuration for X-ray laser experiments

    International Nuclear Information System (INIS)

    Seppala, L.G.

    1985-01-01

    X-ray laser experiments imposed a new demand on the Novette focusing optics. These optics had to provide highly uniform, double-sided illumination on a target region 1.0 cm long by 100 to 200 μm wide. This line focus requirement had to be achieved without degrading the diagnostic reflection from the last surface of the focus lens and without potential ghost focus problems. The only optical configuration that preserves the diagnostic reflection is shown. A negative focal length cylinder lens is placed between the focus lens and the debris shield, with the concave surface facing toward the focus lens. Any ghost reflections from the cylinder lens or debris shield are degraded by astigmatism, making them less hazardous. In practice, the uniformity of illumination is probably about the same for a positive or a negative cylinder lens. The minimum Novette focused spot was approximately 50 to 75 μm in diameter, and the fabrication errors in the 80-cm-diam precision cylinder lens produced a line focus 25 μm wide. a negative cylinder lens design was chosen, however, to optimize the illumination uniformity in the case of line widths of several hundred microns

  1. Stressor-induced proteome alterations in zebrafish: A meta-analysis of response patterns

    Energy Technology Data Exchange (ETDEWEB)

    Groh, Ksenia J., E-mail: ksenia.groh@eawag.ch [Eawag, Swiss Federal Institute of Aquatic Science and Technology, 8600 Dübendorf (Switzerland); ETH Zürich, Swiss Federal Institute of Technology, Department of Chemistry and Applied Biosciences, 8093 Zürich (Switzerland); Suter, Marc J.-F. [Eawag, Swiss Federal Institute of Aquatic Science and Technology, 8600 Dübendorf (Switzerland); ETH Zürich, Swiss Federal Institute of Technology, Department of Environmental Systems Science, 8092 Zürich (Switzerland)

    2015-02-15

    . We suggest that the results of any differential proteomics experiment performed with zebrafish should be interpreted keeping in mind the list of the most frequent responders that we have identified. Similar reservations should apply to any other species where proteome responses are analyzed by global proteomics methods. Careful consideration of the reliability and significance of observed changes is necessary in order not to over-interpret the experimental results and to prevent the proliferation of false positive linkages between the chemical and the cellular functions it perturbs. We further discuss the implications of the identified “top lists” of frequently responding proteins and protein families, and suggest further directions for proteomics research in ecotoxicology. Apart from improving the proteome coverage, further research should focus on defining the significance of the observed stress response patterns for organism phenotypes and on searching for common upstream regulators that can be targeted by specific assays.

  2. Stressor-induced proteome alterations in zebrafish: A meta-analysis of response patterns

    International Nuclear Information System (INIS)

    Groh, Ksenia J.; Suter, Marc J.-F.

    2015-01-01

    . We suggest that the results of any differential proteomics experiment performed with zebrafish should be interpreted keeping in mind the list of the most frequent responders that we have identified. Similar reservations should apply to any other species where proteome responses are analyzed by global proteomics methods. Careful consideration of the reliability and significance of observed changes is necessary in order not to over-interpret the experimental results and to prevent the proliferation of false positive linkages between the chemical and the cellular functions it perturbs. We further discuss the implications of the identified “top lists” of frequently responding proteins and protein families, and suggest further directions for proteomics research in ecotoxicology. Apart from improving the proteome coverage, further research should focus on defining the significance of the observed stress response patterns for organism phenotypes and on searching for common upstream regulators that can be targeted by specific assays

  3. Proteomic screening of human targets of viral microRNAs reveals functions associated with immune evasion and angiogenesis.

    Directory of Open Access Journals (Sweden)

    Amelia M Gallaher

    Full Text Available Kaposi's sarcoma (KS is caused by infection with Kaposi's sarcoma-associated herpesvirus (KSHV. The virus expresses unique microRNAs (miRNAs, but the targets and functions of these miRNAs are not completely understood. In order to identify human targets of viral miRNAs, we measured protein expression changes caused by multiple KSHV miRNAs using pulsed stable labeling with amino acids in cell culture (pSILAC in primary endothelial cells. This led to the identification of multiple human genes that are repressed at the protein level, but not at the miRNA level. Further analysis also identified that KSHV miRNAs can modulate activity or expression of upstream regulatory factors, resulting in suppressed activation of a protein involved in leukocyte recruitment (ICAM1 following lysophosphatidic acid treatment, as well as up-regulation of a pro-angiogenic protein (HIF1α, and up-regulation of a protein involved in stimulating angiogenesis (HMOX1. This study aids in our understanding of miRNA mechanisms of repression and miRNA contributions to viral pathogenesis.

  4. Tracking considerations for fixed target B experiments at SSC and LHC

    International Nuclear Information System (INIS)

    McManus, A.P.; Conetti, S.; Corti, G.; Cox, B.; Dukes, E.C.; Lawry, T.; Nelson, K.; Tzamouranis, I.

    1993-01-01

    Fixed target beauty (B) experiments proposed at the SSC or LHC come in two basic types. Extracted beam experiments use a bent crystal of silicon or some other method to extract a beam of protons parasitically from the circulating beam as the collider experiments are taking data. The two chief extracted beam experiments are the LHB collaboration at the LHC and the SFT collaboration at the SSC. The second type of fixed target experiment places the detector around the circulating beam using a gas jet or thin wire(s) as a target. The (GAJET) experiment proposed at CERN for LHC and the Hera-B experiment at DESY are of this type

  5. Pilot Study on Mass Spectrometry–Based Analysis of the Proteome of CD34+CD123+ Progenitor Cells for the Identification of Potential Targets for Immunotherapy in Acute Myeloid Leukemia

    Directory of Open Access Journals (Sweden)

    Johannes R. Schmidt

    2018-02-01

    Full Text Available Targeting of leukemic stem cells with specific immunotherapy would be an ideal approach for the treatment of myeloid malignancies, but suitable epitopes are unknown. The comparative proteome-level characterization of hematopoietic stem and progenitor cells from healthy stem cell donors and patients with acute myeloid leukemia has the potential to reveal differentially expressed proteins which can be used as surface-markers or as proxies for affected molecular pathways. We employed mass spectrometry methods to analyze the proteome of the cytosolic and the membrane fraction of CD34 and CD123 co-expressing FACS-sorted leukemic progenitors from five patients with acute myeloid leukemia. As a reference, CD34+CD123+ normal hematopoietic progenitor cells from five healthy, granulocyte-colony stimulating factor (G-CSF mobilized stem cell donors were analyzed. In this Tandem Mass Tag (TMT 10-plex labelling–based approach, 2070 proteins were identified with 171 proteins differentially abundant in one or both cellular compartments. This proof-of-principle-study demonstrates the potential of mass spectrometry to detect differentially expressed proteins in two compartment fractions of the entire proteome of leukemic stem cells, compared to their non-malignant counterparts. This may contribute to future immunotherapeutic target discoveries and individualized AML patient characterization.

  6. Optical system for Argus 355-nm 90-mm aperture target-illumination experiments

    Energy Technology Data Exchange (ETDEWEB)

    Johnson, B.C.; Boyd, R.; Hermes, G.; Hildum, J.S.; Linford, G.; Martin, W.E.

    1982-02-01

    The requirements of laser alignment, crystal tuning, target alignment, and laser beam diagnosis are provided by this optical system. Initial setup and preshot alignment techniques are discussed. Layout and operation are contrasted with the 532 nm target experiments.

  7. Genomes to Proteomes

    Energy Technology Data Exchange (ETDEWEB)

    Panisko, Ellen A. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Grigoriev, Igor [USDOE Joint Genome Inst., Walnut Creek, CA (United States); Daly, Don S. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Webb-Robertson, Bobbie-Jo [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Baker, Scott E. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States)

    2009-03-01

    Biologists are awash with genomic sequence data. In large part, this is due to the rapid acceleration in the generation of DNA sequence that occurred as public and private research institutes raced to sequence the human genome. In parallel with the large human genome effort, mostly smaller genomes of other important model organisms were sequenced. Projects following on these initial efforts have made use of technological advances and the DNA sequencing infrastructure that was built for the human and other organism genome projects. As a result, the genome sequences of many organisms are available in high quality draft form. While in many ways this is good news, there are limitations to the biological insights that can be gleaned from DNA sequences alone; genome sequences offer only a bird's eye view of the biological processes endemic to an organism or community. Fortunately, the genome sequences now being produced at such a high rate can serve as the foundation for other global experimental platforms such as proteomics. Proteomic methods offer a snapshot of the proteins present at a point in time for a given biological sample. Current global proteomics methods combine enzymatic digestion, separations, mass spectrometry and database searching for peptide identification. One key aspect of proteomics is the prediction of peptide sequences from mass spectrometry data. Global proteomic analysis uses computational matching of experimental mass spectra with predicted spectra based on databases of gene models that are often generated computationally. Thus, the quality of gene models predicted from a genome sequence is crucial in the generation of high quality peptide identifications. Once peptides are identified they can be assigned to their parent protein. Proteins identified as expressed in a given experiment are most useful when compared to other expressed proteins in a larger biological context or biochemical pathway. In this chapter we will discuss the automatic

  8. Targeted changes of the cell wall proteome influence Candida albicans ability to form single- and multi-strain biofilms.

    Directory of Open Access Journals (Sweden)

    Vitor Cabral

    2014-12-01

    Full Text Available Biofilm formation is an important virulence trait of the pathogenic yeast Candida albicans. We have combined gene overexpression, strain barcoding and microarray profiling to screen a library of 531 C. albicans conditional overexpression strains (∼10% of the genome for genes affecting biofilm development in mixed-population experiments. The overexpression of 16 genes increased strain occupancy within a multi-strain biofilm, whereas overexpression of 4 genes decreased it. The set of 16 genes was significantly enriched for those encoding predicted glycosylphosphatidylinositol (GPI-modified proteins, namely Ihd1/Pga36, Phr2, Pga15, Pga19, Pga22, Pga32, Pga37, Pga42 and Pga59; eight of which have been classified as pathogen-specific. Validation experiments using either individually- or competitively-grown overexpression strains revealed that the contribution of these genes to biofilm formation was variable and stage-specific. Deeper functional analysis of PGA59 and PGA22 at a single-cell resolution using atomic force microscopy showed that overexpression of either gene increased C. albicans ability to adhere to an abiotic substrate. However, unlike PGA59, PGA22 overexpression led to cell cluster formation that resulted in increased sensitivity to shear forces and decreased ability to form a single-strain biofilm. Within the multi-strain environment provided by the PGA22-non overexpressing cells, PGA22-overexpressing cells were protected from shear forces and fitter for biofilm development. Ultrastructural analysis, genome-wide transcript profiling and phenotypic analyses in a heterologous context suggested that PGA22 affects cell adherence through alteration of cell wall structure and/or function. Taken together, our findings reveal that several novel predicted GPI-modified proteins contribute to the cooperative behaviour between biofilm cells and are important participants during C. albicans biofilm formation. Moreover, they illustrate the power

  9. Remote manipulator experience in target train maintenance at Fermilab

    International Nuclear Information System (INIS)

    Butala, S.W.

    1984-01-01

    When Fermilab was designed in the late 1960's and early 1970's, it was anticipated that Neutrino target train servicing could be costly in terms of personnel radiation exposure. This was based in part on the expectation that target intensities of at least 1E13 protons/pulse would be required to produce several neutrino interactions in a large bubble chamber detector. This was indeed later proven to be the case and historically the Neutrino beamline has been targeted with about one half of the protons available from the Main Ring. It was believed that much of the occupational radiation dose from the Neutrino Area could be spared by utilization of a remote manipulator system, which was eventually installed. It is the purpose of this report to examine the use of the Fermilab remote manipulator system and evaluate its cost effectiveness and success as an ALARA (As Low As Reasonably Achievable) tool. 16 references, 11 figures

  10. Targets and Witnesses: Middle School Students' Sexual Harassment Experiences

    Science.gov (United States)

    Lichty, Lauren F.; Campbell, Rebecca

    2012-01-01

    School-based peer-to-peer sexual harassment (SH) emerged as an issue of concern in the early 1990s. As a developing field, this literature has several notable gaps. The current study extends previous research by, (a) exploring the understudied experiences of middle school students, (b) assessing students' experiences witnessing SH, and (c)…

  11. SuperQuant-assisted comparative proteome analysis of glioblastoma subpopulations allows for identification of potential novel therapeutic targets and cell markers

    DEFF Research Database (Denmark)

    Verano-Braga, Thiago; Gorshkov, Vladimir; Munthe, Sune

    2018-01-01

    Glioblastoma (GBM) is a highly aggressive brain cancer with poor prognosis and low survival rate. Invasive cancer stem-like cells (CSCs) are responsible for tumor recurrence because they escape current treatments. Our main goal was to study the proteome of three GBM subpopulations to identify key...... molecules behind GBM cell phenotypes and potential cell markers for migrating cells. We used SuperQuant-an enhanced quantitative proteome approach-to increase proteome coverage. We found 148 proteins differentially regulated in migrating CSCs and 199 proteins differentially regulated in differentiated cells...... migration. Moreover, our data suggested that microRNA-122 (miR-122) is a potential upstream regulator of GBM phenotypes as miR-122 activation was predicted for differentiated cells while its inhibition was predicted for migrating CSCs. Finally, we validated transferrin (TF) and procollagen-lysine 2...

  12. Contributed Review: The novel gas puff targets for laser-matter interaction experiments

    Energy Technology Data Exchange (ETDEWEB)

    Wachulak, Przemyslaw W., E-mail: wachulak@gmail.com [Institute of Optoelectronics, Military University of Technology, Ul. Gen. S. Kaliskiego 2, 00-908 Warsaw (Poland)

    2016-09-15

    Various types of targetry are used nowadays in laser matter interaction experiments. Such targets are characterized using different methods capable of acquiring information about the targets such as density, spatial distribution, and temporal behavior. In this mini-review paper, a particular type of target will be presented. The targets under consideration are gas puff targets of various and novel geometries. Those targets were investigated using extreme ultraviolet (EUV) and soft X-ray (SXR) imaging techniques, such as shadowgraphy, tomography, and pinhole camera imaging. Details about characterization of those targets in the EUV and SXR spectral regions will be presented.

  13. The proteome of human saliva

    Science.gov (United States)

    Griffin, Timothy J.

    2013-05-01

    Human saliva holds tremendous potential for transforming disease and health diagnostics given its richness of molecular information and non-invasive collection. Enumerating its molecular constituents is an important first step towards reaching this potential. Among the molecules in saliva, proteins and peptides arguably have the most value: they can directly indicate biochemical functions linked to a health condition/disease state, and they are attractive targets for biomarker assay development. However, cataloging and defining the human salivary proteome is challenging given the dynamic, chemically heterogeneous and complex nature of the system. In addition, the overall human saliva proteome is composed of several "sub-proteomes" which include: intact full length proteins, proteins carrying post-translational modifications (PTMs), low molecular weight peptides, and the metaproteome, derived from protein products from nonhuman organisms (e.g. microbes) present in the oral cavity. Presented here will be a summary of communal efforts to meet the challenge of characterizing the multifaceted saliva proteome, focusing on the use of mass spectrometry as the proteomic technology of choice. Implications of these efforts to characterize the salivary proteome in the context of disease diagnostics will also be discussed.

  14. Proteomics of Aggregatibacter actinomycetemcomitans Outer Membrane Vesicles.

    Directory of Open Access Journals (Sweden)

    Thomas Kieselbach

    Full Text Available Aggregatibacter actinomycetemcomitans is an oral and systemic pathogen associated with aggressive forms of periodontitis and with endocarditis. Outer membrane vesicles (OMVs released by this species have been demonstrated to deliver effector proteins such as cytolethal distending toxin (CDT and leukotoxin (LtxA into human host cells and to act as triggers of innate immunity upon carriage of NOD1- and NOD2-active pathogen-associated molecular patterns (PAMPs. To improve our understanding of the pathogenicity-associated functions that A. actinomycetemcomitans exports via OMVs, we studied the proteome of density gradient-purified OMVs from a rough-colony type clinical isolate, strain 173 (serotype e using liquid chromatography-tandem mass spectrometry (LC-MS/MS. This analysis yielded the identification of 151 proteins, which were found in at least three out of four independent experiments. Data are available via ProteomeXchange with identifier PXD002509. Through this study, we not only confirmed the vesicle-associated release of LtxA, and the presence of proteins, which are known to act as immunoreactive antigens in the human host, but we also identified numerous additional putative virulence-related proteins in the A. actinomycetemcomitans OMV proteome. The known and putative functions of these proteins include immune evasion, drug targeting, and iron/nutrient acquisition. In summary, our findings are consistent with an OMV-associated proteome that exhibits several offensive and defensive functions, and they provide a comprehensive basis to further disclose roles of A. actinomycetemcomitans OMVs in periodontal and systemic disease.

  15. Few-body experiments with polarized beams and polarized targets

    International Nuclear Information System (INIS)

    Simmons, J.E.

    1983-01-01

    A survey is presented concerning recent polarization experiments in the elastic p-d, p- 3 He, and p- 4 He systems. Mention is made of selected neutron experiments. The nominal energy range is 10 to 1000 MeV. Recent results and interpretations of the p-d system near 10 MeV are discussed. New experiments on the energy dependence of back angle p-d tensor polarization are discussed with respect to resolution of discrepancies and difficulty of theoretical interpretation. Progress is noted concerning multiple scattering interpretation of forward p-d deuteron polarization. Some new results are presented concerning the p- 3 He system and higher energy p- 4 He polarization experiments. 52 references

  16. Secondary emission detectors for fixed target experiments at Fermilab

    International Nuclear Information System (INIS)

    Drucker, R.; Ford, R.; Tassotto, G.

    1998-02-01

    A description of a Secondary Emission Electron Detector (SEED) is given. The SEEDs provide accurate profiles and positions at small wire spacing (125-500 mm) in a high energy, high rate environment that exceeds the capabilities of traditional segmented wire ion chambers (SWICs). This device has been designed and constructed to monitor beam position and profile of two fixed target beamlines, namely, KTeV (FNAL E-799, E-832) with an average beam sigma at target of 0.22 mm and NuTeV (FNAL E-815) with a sigma = 0.6 mm. KTeV took beam at an intensity of up to 5E12 800 GeV protons over a 20 sec spill and NuTeV received 1E13 800 GeV protons in five pings/spill

  17. The tagged photon beam polarization of the jet target experiment

    International Nuclear Information System (INIS)

    Bianchi, N.; Muccifora, V.

    1989-01-01

    The applicability of the residual electron selection method to the tagging method of the jet target laboratory has been studied. With this end in view the behaviour of the polarized bremsstrahlung cross section in the range considered has been analysed, while the polarization increase by means of the RES has been evaluated. The vertical conditions of the focusing of the tagging spectrometer as a function of energy have been determined. Finally the gamma beam density and the tagging efficiency have been calculated

  18. First Nuclear Reaction Experiment with Stored Radioactive 56Ni Beam and Internal Hydrogen and Helium Targets

    NARCIS (Netherlands)

    Egelhof, P.; Bagchi, Soumya; Csatlós, M.; Dillmann, I.; Dimopoulou, C.; Furuno, T; Geissel, H.; Gernhauser, R.; Kalantar-Nayestanaki, Nasser; Kuilman, M.; Mahjour-Shafiei, M.; Najafi, M.A.; Rigollet, C.; Streicher, B.

    2014-01-01

    The investigation of light-ion induced direct reactions using stored and cooled radioactive beams, interacting with internal targets of storage rings, can lead to substantial advantages over external target experiments, in particular for direct reaction experiments in inverse kinematics at very low

  19. Parametric investigations of target normal sheath acceleration experiments

    International Nuclear Information System (INIS)

    Zani, Alessandro; Sgattoni, Andrea; Passoni, Matteo

    2011-01-01

    One of the most important challenges related to laser-driven ion acceleration research is to actively control some important ion beam features. This is a peculiar topic in the light of future possible technological applications. In the present work we make use of one theoretical model for target normal sheath acceleration in order to reproduce recent experimental parametric studies about maximum ion energy dependencies on laser parameters. The key role played by pulse energy and intensity is enlightened. Finally the effective dependence of maximum ion energy on intensity is evaluated using a combined theoretical approach, obtained by means of an analytical and a particle-in-cell numerical investigation.

  20. Parametric investigations of target normal sheath acceleration experiments

    Science.gov (United States)

    Zani, Alessandro; Sgattoni, Andrea; Passoni, Matteo

    2011-10-01

    One of the most important challenges related to laser-driven ion acceleration research is to actively control some important ion beam features. This is a peculiar topic in the light of future possible technological applications. In the present work we make use of one theoretical model for target normal sheath acceleration in order to reproduce recent experimental parametric studies about maximum ion energy dependencies on laser parameters. The key role played by pulse energy and intensity is enlightened. Finally the effective dependence of maximum ion energy on intensity is evaluated using a combined theoretical approach, obtained by means of an analytical and a particle-in-cell numerical investigation.

  1. Muon-catalyzed fusion experiment target and detector system. Preliminary design report

    International Nuclear Information System (INIS)

    Jones, S.E.; Watts, K.D.; Caffrey, A.J.; Walter, J.B.

    1982-03-01

    We present detailed plans for the target and particle detector systems for the muon-catalyzed fusion experiment. Requirements imposed on the target vessel by experimental conditions and safety considerations are delineated. Preliminary designs for the target vessel capsule and secondary containment vessel have been developed which meet these requirements. In addition, the particle detection system is outlined, including associated fast electronics and on-line data acquisition. Computer programs developed to study the target and detector system designs are described

  2. Clinical veterinary proteomics: Techniques and approaches to decipher the animal plasma proteome.

    Science.gov (United States)

    Ghodasara, P; Sadowski, P; Satake, N; Kopp, S; Mills, P C

    2017-12-01

    Over the last two decades, technological advancements in the field of proteomics have advanced our understanding of the complex biological systems of living organisms. Techniques based on mass spectrometry (MS) have emerged as powerful tools to contextualise existing genomic information and to create quantitative protein profiles from plasma, tissues or cell lines of various species. Proteomic approaches have been used increasingly in veterinary science to investigate biological processes responsible for growth, reproduction and pathological events. However, the adoption of proteomic approaches by veterinary investigators lags behind that of researchers in the human medical field. Furthermore, in contrast to human proteomics studies, interpretation of veterinary proteomic data is difficult due to the limited protein databases available for many animal species. This review article examines the current use of advanced proteomics techniques for evaluation of animal health and welfare and covers the current status of clinical veterinary proteomics research, including successful protein identification and data interpretation studies. It includes a description of an emerging tool, sequential window acquisition of all theoretical fragment ion mass spectra (SWATH-MS), available on selected mass spectrometry instruments. This newly developed data acquisition technique combines advantages of discovery and targeted proteomics approaches, and thus has the potential to advance the veterinary proteomics field by enhancing identification and reproducibility of proteomics data. Copyright © 2017 Elsevier Ltd. All rights reserved.

  3. Light dark sector at colliders and fixed target experiments

    OpenAIRE

    Darmé, Luc; Rao, Soumya; Roszkowski, Leszek

    2018-01-01

    Minimal scenarios with light (sub-GeV) thermal dark matter are usually accompanied by a correspondingly light "dark sector". Taking as an example a simple fermionic dark matter model, we will show that the presence of the dark sector plays a key role in constraining such scenarios at accelerators experiments. The effect of including a dark Higgs boson in the light spectrum is in particular investigated.

  4. CENTRAL BANK INDEPENDENCE AND INFLATION TARGETING - THE BRITISH EXPERIENCE

    Directory of Open Access Journals (Sweden)

    David Delia

    2010-07-01

    Full Text Available Known as the ‘Old Lady’ of Threadneedle Street, the Bank of England is the central bank of the United Kingdom. Founded in 1694, the Bank of England is standing at the centre of the United Kingdom’s financial system, and is committed to promoting and maintaining monetary and financial stability as its contribution to a healthy economy. In our opinion, it is very important to analyze the Bank of England’s monetary policy strategy, starting from 1992 – adoption of the inflation target and the evolution of it’s monetary policy strategy, through an important feature – delegating operational accountability regarding the monetary policy in 1997 as well as the appropriate institutional framework. More over, it is important to analyze the Bank of England’s performances before and after granting central bank independence.

  5. Experience of targeted Usher exome sequencing as a clinical test

    Science.gov (United States)

    Besnard, Thomas; García-García, Gema; Baux, David; Vaché, Christel; Faugère, Valérie; Larrieu, Lise; Léonard, Susana; Millan, Jose M; Malcolm, Sue; Claustres, Mireille; Roux, Anne-Françoise

    2014-01-01

    We show that massively parallel targeted sequencing of 19 genes provides a new and reliable strategy for molecular diagnosis of Usher syndrome (USH) and nonsyndromic deafness, particularly appropriate for these disorders characterized by a high clinical and genetic heterogeneity and a complex structure of several of the genes involved. A series of 71 patients including Usher patients previously screened by Sanger sequencing plus newly referred patients was studied. Ninety-eight percent of the variants previously identified by Sanger sequencing were found by next-generation sequencing (NGS). NGS proved to be efficient as it offers analysis of all relevant genes which is laborious to reach with Sanger sequencing. Among the 13 newly referred Usher patients, both mutations in the same gene were identified in 77% of cases (10 patients) and one candidate pathogenic variant in two additional patients. This work can be considered as pilot for implementing NGS for genetically heterogeneous diseases in clinical service. PMID:24498627

  6. Shock-ignition relevant experiments with planar targets on OMEGA

    Energy Technology Data Exchange (ETDEWEB)

    Hohenberger, M.; Hu, S. X.; Anderson, K. S.; Boehly, T. R.; Sangster, T. C.; Seka, W.; Stoeckl, C.; Yaakobi, B. [Laboratory for Laser Energetics, University of Rochester, 250 East River Road, Rochester, New York 14623 (United States); Theobald, W.; Lafon, M.; Nora, R. [Laboratory for Laser Energetics, University of Rochester, 250 East River Road, Rochester, New York 14623 (United States); Fusion Science Center, University of Rochester, Rochester, New York 14623 (United States); Betti, R.; Meyerhofer, D. D. [Laboratory for Laser Energetics, University of Rochester, 250 East River Road, Rochester, New York 14623 (United States); Fusion Science Center, University of Rochester, Rochester, New York 14623 (United States); Departments of Mechanical Engineering and Physics, University of Rochester, Rochester, New York 14627 (United States); Casner, A. [CEA, DAM, DIF, Arpajon (France); Fratanduono, D. E. [Lawrence Livermore National Laboratory, P.O. Box 808, Livermore, California 94550 (United States); Ribeyre, X.; Schurtz, G. [Centre Lasers Intenses et Applications, CELIA, Université Bordeaux 1-CEA-CNRS, Talence (France)

    2014-02-15

    We report on laser-driven, strong-shock generation and hot-electron production in planar targets in the presence of a pre-plasma at shock-ignition (SI) relevant laser and pre-plasma conditions. 2-D simulations reproduce the shock dynamics well, indicating ablator shocks of up to 75 Mbar have been generated. We observe hot-electron temperatures of ∼70 keV at intensities of 1.4 × 10{sup 15} W/cm{sup 2} with multiple overlapping beams driving the two-plasmon decay instability. When extrapolated to SI-relevant intensities of ∼10{sup 16} W/cm{sup 2}, the hot electron temperature will likely exceed 100 keV, suggesting that tightly focused beams without overlap are better suited for launching the ignitor shock.

  7. SKIN TOXICITY OF TARGETED THERAPY: VEMURAFENIB, FIRST EXPERIENCES FROM MONTENEGRO

    Directory of Open Access Journals (Sweden)

    Todorović Vladimir

    2015-07-01

    Full Text Available Introduction: Data on melanoma incidence and mortality in Montenegro is only partially complete. GLOBOCAN and EUCAN reports estimate melanoma incidence in Montenegro to be between 4.6-7.3 cases/100 000. At least 50% of all metastatic melanoma cell lines carry an activating mutation in the BRAF oncogene. The treatment of advanced melanoma with the selective BRAF inhibitors, such as vemurafenib demonstrated improvement in progression free interval and overall survival when compared to conventional chemotherapy treatment. Up to 95% of patients treated with vemurafenib experience skin toxicity. Material and methods: Five patients with metastatic melanoma have been treated with vemurafenib at the Clinic for Oncology and Radiotherapy Podgorica, Montenegro, during the period 2013-2014. They were treated with standard dose (960 mg twice a day, per os. Data about the occurrence and management of skin side-effects in these patients were retrospectively collected from medical charts. Severity of side-effects was graded using the National Cancer Institute's Common Terminology Criteria for Adverse Events, version 4.0. Results: In 2013, 41 new cases of melanoma were registered in Montenegro, 20 (48.7% male and 21 (51.3% female. In 2014, 49 new cases of melanoma were registered, 27 (55.1% male and 22 (44.9% female. Two out of five (40% vemurafenib treated patients experienced photosensitivity, three (60% had rash eruptions, four (80% developed alopecia, and two (40% had dry skin problems. Alteration in nevus color and size occurred in one (20% patient, and two (40% patients developed new pigmented lesions. Conclusion: Skin side effects associated with vemurafenib are plentiful, but generally manageable with supportive care measures. In our experience, majority of described side-effects were of grade 1 or 2, and none required dose modifications, or discontinuation of the therapy. Our experience suggests that patients taking BRAF inhibitors should have regular

  8. Fixed target experiments with heavy ions at CERN

    International Nuclear Information System (INIS)

    Bialkowska, H.

    1997-11-01

    A concise review of recent results from CERN experiments with relativistic ion beams, from oxygen and sulphur up to lead, at 160 and 200 GeV/c/N, is presented. Both leptonic and hadronic signals are reviewed. Two results from leptonic signals look very promising. One is an excess (over conventional expectations) in the invariant mass spectrum of electron pairs produced in nuclear collisions, for masses up to 1.5 GeV. Another is a strong psi resonance suppression, observed in central lead-lead collisions. These effects could possibly indicate the importance of partonic degrees of freedom, and may be a harbinger of the quark-gluon plasma creation. The hadronic signals concern the nuclear stopping power, transverse mass spectra and their relation to temperature, strange particle production and particle source sizes, as determined by the interferometric method. (author)

  9. Color film spectral properties test experiment for target simulation

    Science.gov (United States)

    Liu, Xinyue; Ming, Xing; Fan, Da; Guo, Wenji

    2017-04-01

    In hardware-in-loop test of the aviation spectra camera, the liquid crystal light valve and digital micro-mirror device could not simulate the spectrum characteristics of the landmark. A test system frame was provided based on the color film for testing the spectra camera; and the spectrum characteristics of the color film was test in the paper. The result of the experiment shows that difference was existed between the landmark and the film spectrum curse. However, the spectrum curse peak should change according to the color, and the curse is similar with the standard color traps. So, if the quantity value of error between the landmark and the film was calibrated and the error could be compensated, the film could be utilized in the hardware-in-loop test for the aviation spectra camera.

  10. Beauty hadroproduction at fixed target in the WA92 experiment

    International Nuclear Information System (INIS)

    Gemme, C.

    1999-01-01

    Using a sample of 10 8 triggered events, produced in π-Cu interactions at 350 GeV/c, we have identified 26 beauty events. The estimated background in this sample is 0.6 ± 0.6 events. From these data, assuming a linear A-dependence, we measure a beauty production cross-section integrated over all x F of 5.7 +1.3 -1.1 (stat.) +0.6 -0.5 (syst.) nb/N. Differential distributions with respect to x F and p 2 T have been determined as well as some two-particle kinematic variables. Our results are compared with previous experiments and with a next-to-leading-order QCD calculation

  11. Commissioning experiment of the polarized internal gas target with deuterium at ANKE/COSY

    Energy Technology Data Exchange (ETDEWEB)

    Gou, Boxing [Institut fuer Kernphysik, Forschungszentrum Juelich (Germany); Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou (China); Collaboration: ANKE-Collaboration

    2012-07-01

    In order to conduct the production experiments with polarized deuterium target and (un)polarized proton beam at ANKE/COSY, a commissioning experiment of the polarized internal target with deuterium is imperative. The commissioning experiment includes the measurements of both the vector (Q{sub y}) and tensor (Q{sub yy}) polarization of the deuterium gas target through the nuclear reactions with large and well known analyzing powers, which can be detected in ANKE. The dependence of the polarizations along the storage cell is also determined. The poster presents the physics case for the experiments with deuterium polarized internal target and the apparatus needed for the commissioning experiment, as well as the procedure of extraction for spin observables.

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

    Science.gov (United States)

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

    2009-12-01

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

  13. A Probabilistic Framework for Peptide and Protein Quantification from Data-Dependent and Data-Independent LC-MS Proteomics Experiments

    Science.gov (United States)

    Richardson, Keith; Denny, Richard; Hughes, Chris; Skilling, John; Sikora, Jacek; Dadlez, Michał; Manteca, Angel; Jung, Hye Ryung; Jensen, Ole Nørregaard; Redeker, Virginie; Melki, Ronald; Langridge, James I.; Vissers, Johannes P.C.

    2013-01-01

    A probability-based quantification framework is presented for the calculation of relative peptide and protein abundance in label-free and label-dependent LC-MS proteomics data. The results are accompanied by credible intervals and regulation probabilities. The algorithm takes into account data uncertainties via Poisson statistics modified by a noise contribution that is determined automatically during an initial normalization stage. Protein quantification relies on assignments of component peptides to the acquired data. These assignments are generally of variable reliability and may not be present across all of the experiments comprising an analysis. It is also possible for a peptide to be identified to more than one protein in a given mixture. For these reasons the algorithm accepts a prior probability of peptide assignment for each intensity measurement. The model is constructed in such a way that outliers of any type can be automatically reweighted. Two discrete normalization methods can be employed. The first method is based on a user-defined subset of peptides, while the second method relies on the presence of a dominant background of endogenous peptides for which the concentration is assumed to be unaffected. Normalization is performed using the same computational and statistical procedures employed by the main quantification algorithm. The performance of the algorithm will be illustrated on example data sets, and its utility demonstrated for typical proteomics applications. The quantification algorithm supports relative protein quantification based on precursor and product ion intensities acquired by means of data-dependent methods, originating from all common isotopically-labeled approaches, as well as label-free ion intensity-based data-independent methods. PMID:22871168

  14. Spin and diffractive physics with a fixed-target experiment at the LHC (AFTER-LHC)

    Energy Technology Data Exchange (ETDEWEB)

    Lorce, C.; Chambert, V.; Didelez, J. P.; Genolini, B.; Hadjidakis, C.; Lansberg, J. P.; Rosier, P. [IPNO, Universite Paris-Sud, CNRS/IN2P3, F-91406, Orsay (France); Anselmino, M.; Arnaldi, R.; Scomparin, E. [INFN Sez. Torino, Via P. Giuria 1,1-10125, Torino (Italy); Brodsky, S. J. [SLAC National Accelerator Laboratory, Stanford U, Stanford, CA 94309, (United States); Ferreiro, E. G. [Departamento de Fisica de Particulas, Univ. de Santiago de C, 15782 Santiago de C (Spain); Fleuret, F. [Laboratoire Leprince Ringuet, Ecole Polytechnique, CNRS/IN2P3, 91128 Palaiseau (France); Rakotozafindrabe, A. [IRFU/SPhN, CFA Society, 91191 Gifsur-Yvette Cedex (France); Schienbein, I. [LPSC, Universite Joseph Fourier, CNRS/IN2P3/INPG, F-38026 Grenoble (France); Uggerhoj, U. I. [Department of Physics and Astronomy, University of Aarhus (Denmark)

    2013-04-15

    We report on the spin and diffractive physics at a future multi-purpose f xed-target experiment with proton and lead LHC beams extracted by a bent crystal. The LHC multi-TeV beams allow for the most energetic f xed-target experiments ever performed, opening new domains of particle and nuclear physics and complementing that of collider physics, in particular that of RHIC and the EIC projects. The luminosity achievable with AFTER using typical targets would surpass that of RHIC by more than 3 orders of magnitude. The f xed-target mode has the advantage to allow for measurements of single-spin asymmetries with polarized target as well as of single-diffractive processes in the target region.

  15. Spin and diffractive physics with a fixed-target experiment at the LHC (AFTER-LHC)

    International Nuclear Information System (INIS)

    Lorcé, C.; Chambert, V.; Didelez, J. P.; Genolini, B.; Hadjidakis, C.; Lansberg, J. P.; Rosier, P.; Anselmino, M.; Arnaldi, R.; Scomparin, E.; Brodsky, S. J.; Ferreiro, E. G.; Fleuret, F.; Rakotozafindrabe, A.; Schienbein, I.; Uggerhøj, U. I.

    2013-01-01

    We report on the spin and diffractive physics at a future multi-purpose f xed-target experiment with proton and lead LHC beams extracted by a bent crystal. The LHC multi-TeV beams allow for the most energetic f xed-target experiments ever performed, opening new domains of particle and nuclear physics and complementing that of collider physics, in particular that of RHIC and the EIC projects. The luminosity achievable with AFTER using typical targets would surpass that of RHIC by more than 3 orders of magnitude. The f xed-target mode has the advantage to allow for measurements of single-spin asymmetries with polarized target as well as of single-diffractive processes in the target region.

  16. Systematic Analysis of Intracellular-targeting Antimicrobial Peptides, Bactenecin 7, Hybrid of Pleurocidin and Dermaseptin, Proline-Arginine-rich Peptide, and Lactoferricin B, by Using Escherichia coli Proteome Microarrays.

    Science.gov (United States)

    Ho, Yu-Hsuan; Shah, Pramod; Chen, Yi-Wen; Chen, Chien-Sheng

    2016-06-01

    Antimicrobial peptides (AMPs) act either through membrane lysis or by attacking intracellular targets. Intracellular targeting AMPs are a resource for antimicrobial agent development. Several AMPs have been identified as intracellular targeting peptides; however, the intracellular targets of many of these peptides remain unknown. In the present study, we used an Escherichia coli proteome microarray to systematically identify the protein targets of three intracellular targeting AMPs: bactenecin 7 (Bac7), a hybrid of pleurocidin and dermaseptin (P-Der), and proline-arginine-rich peptide (PR-39). In addition, we also included the data of lactoferricin B (LfcinB) from our previous study for a more comprehensive analysis. We analyzed the unique protein hits of each AMP in the Kyoto Encyclopedia of Genes and Genomes. The results indicated that Bac7 targets purine metabolism and histidine kinase, LfcinB attacks the transcription-related activities and several cellular carbohydrate biosynthetic processes, P-Der affects several catabolic processes of small molecules, and PR-39 preferentially recognizes proteins involved in RNA- and folate-metabolism-related cellular processes. Moreover, both Bac7 and LfcinB target purine metabolism, whereas LfcinB and PR-39 target lipopolysaccharide biosynthesis. This suggested that LfcinB and Bac7 as well as LfcinB and PR-39 have a synergistic effect on antimicrobial activity, which was validated through antimicrobial assays. Furthermore, common hits of all four AMPs indicated that all of them target arginine decarboxylase, which is a crucial enzyme for Escherichia coli survival in extremely acidic environments. Thus, these AMPs may display greater inhibition to bacterial growth in extremely acidic environments. We have also confirmed this finding in bacterial growth inhibition assays. In conclusion, this comprehensive identification and systematic analysis of intracellular targeting AMPs reveals crucial insights into the intracellular

  17. Systematic Analysis of Intracellular-targeting Antimicrobial Peptides, Bactenecin 7, Hybrid of Pleurocidin and Dermaseptin, Proline–Arginine-rich Peptide, and Lactoferricin B, by Using Escherichia coli Proteome Microarrays*

    Science.gov (United States)

    Ho, Yu-Hsuan; Shah, Pramod; Chen, Yi-Wen; Chen, Chien-Sheng

    2016-01-01

    Antimicrobial peptides (AMPs) act either through membrane lysis or by attacking intracellular targets. Intracellular targeting AMPs are a resource for antimicrobial agent development. Several AMPs have been identified as intracellular targeting peptides; however, the intracellular targets of many of these peptides remain unknown. In the present study, we used an Escherichia coli proteome microarray to systematically identify the protein targets of three intracellular targeting AMPs: bactenecin 7 (Bac7), a hybrid of pleurocidin and dermaseptin (P-Der), and proline-arginine-rich peptide (PR-39). In addition, we also included the data of lactoferricin B (LfcinB) from our previous study for a more comprehensive analysis. We analyzed the unique protein hits of each AMP in the Kyoto Encyclopedia of Genes and Genomes. The results indicated that Bac7 targets purine metabolism and histidine kinase, LfcinB attacks the transcription-related activities and several cellular carbohydrate biosynthetic processes, P-Der affects several catabolic processes of small molecules, and PR-39 preferentially recognizes proteins involved in RNA- and folate-metabolism-related cellular processes. Moreover, both Bac7 and LfcinB target purine metabolism, whereas LfcinB and PR-39 target lipopolysaccharide biosynthesis. This suggested that LfcinB and Bac7 as well as LfcinB and PR-39 have a synergistic effect on antimicrobial activity, which was validated through antimicrobial assays. Furthermore, common hits of all four AMPs indicated that all of them target arginine decarboxylase, which is a crucial enzyme for Escherichia coli survival in extremely acidic environments. Thus, these AMPs may display greater inhibition to bacterial growth in extremely acidic environments. We have also confirmed this finding in bacterial growth inhibition assays. In conclusion, this comprehensive identification and systematic analysis of intracellular targeting AMPs reveals crucial insights into the intracellular

  18. Proteomic profiling of the rat hypothalamus

    Directory of Open Access Journals (Sweden)

    Pedroso Amanda P

    2012-04-01

    Full Text Available Abstract Background The hypothalamus plays a pivotal role in numerous mechanisms highly relevant to the maintenance of body homeostasis, such as the control of food intake and energy expenditure. Impairment of these mechanisms has been associated with the metabolic disturbances involved in the pathogenesis of obesity. Since rodent species constitute important models for metabolism studies and the rat hypothalamus is poorly characterized by proteomic strategies, we performed experiments aimed at constructing a two-dimensional gel electrophoresis (2-DE profile of rat hypothalamus proteins. Results As a first step, we established the best conditions for tissue collection and protein extraction, quantification and separation. The extraction buffer composition selected for proteome characterization of rat hypothalamus was urea 7 M, thiourea 2 M, CHAPS 4%, Triton X-100 0.5%, followed by a precipitation step with chloroform/methanol. Two-dimensional (2-D gels of hypothalamic extracts from four-month-old rats were analyzed; the protein spots were digested and identified by using tandem mass spectrometry and database query using the protein search engine MASCOT. Eighty-six hypothalamic proteins were identified, the majority of which were classified as participating in metabolic processes, consistent with the finding of a large number of proteins with catalytic activity. Genes encoding proteins identified in this study have been related to obesity development. Conclusion The present results indicate that the 2-DE technique will be useful for nutritional studies focusing on hypothalamic proteins. The data presented herein will serve as a reference database for studies testing the effects of dietary manipulations on hypothalamic proteome. We trust that these experiments will lead to important knowledge on protein targets of nutritional variables potentially able to affect the complex central nervous system control of energy homeostasis.

  19. Laboratory facility for production of cryogenic targets for hot plasma experiments

    International Nuclear Information System (INIS)

    Sadowski, M.; Szydlowski, A.; Jakubowski, L.; Cwiek, E.

    1990-10-01

    Results of preliminary operational tests of the cryogenic stand designed for the production of small droplets of liquid hydrogen or deuterium are presented. Such cryogenic micro-targets are needed for nuclear and thermonuclear experiments. (author)

  20. Hadroproduction and photoproduction of beauty and charm in fixed-target experiments

    International Nuclear Information System (INIS)

    Slaughter, J.

    1996-01-01

    The authors summarize the current experimental situation for charm and beauty production in fixed-target experiments. Particular emphasis is placed on beauty cross-sections and charm pair correlations

  1. Maximizing the sensitivity and reliability of peptide identification in large-scale proteomic experiments by harnessing multiple search engines.

    Science.gov (United States)

    Yu, Wen; Taylor, J Alex; Davis, Michael T; Bonilla, Leo E; Lee, Kimberly A; Auger, Paul L; Farnsworth, Chris C; Welcher, Andrew A; Patterson, Scott D

    2010-03-01

    Despite recent advances in qualitative proteomics, the automatic identification of peptides with optimal sensitivity and accuracy remains a difficult goal. To address this deficiency, a novel algorithm, Multiple Search Engines, Normalization and Consensus is described. The method employs six search engines and a re-scoring engine to search MS/MS spectra against protein and decoy sequences. After the peptide hits from each engine are normalized to error rates estimated from the decoy hits, peptide assignments are then deduced using a minimum consensus model. These assignments are produced in a series of progressively relaxed false-discovery rates, thus enabling a comprehensive interpretation of the data set. Additionally, the estimated false-discovery rate was found to have good concordance with the observed false-positive rate calculated from known identities. Benchmarking against standard proteins data sets (ISBv1, sPRG2006) and their published analysis, demonstrated that the Multiple Search Engines, Normalization and Consensus algorithm consistently achieved significantly higher sensitivity in peptide identifications, which led to increased or more robust protein identifications in all data sets compared with prior methods. The sensitivity and the false-positive rate of peptide identification exhibit an inverse-proportional and linear relationship with the number of participating search engines.

  2. Status of the hydrogen and deuterium atomic beam polarized target for NEPTUN experiment

    International Nuclear Information System (INIS)

    Balandikov, N.I.; Ershov, V.P.; Fimushkin, V.V.; Kulikov, M.V.; Pilipenko, Y.K.; Shutov, V.B.

    1995-01-01

    NEPTUN-NEPTUN-A is a polarized experiment at Accelerating and Storage Complex (UNK, IHEP) with two internal targets. Status of the atomic beam polarized target that is being developed at the Joint Institute for Nuclear Research, Dubna is presented. copyright 1995 American Institute of Physics

  3. Repetitive laser fusion experiment and operation using a target injection system

    International Nuclear Information System (INIS)

    Nishimura, Yasuhiko; Komeda, Osamu; Mori, Yoshitaka

    2017-01-01

    Since 2008, a collaborative research project on laser fusion development based on a high-speed ignition method using repetitive laser has been carried out with several collaborative research institutes. This paper reports the current state of operation of high repetition laser fusion experiments, such as target introduction and control based on a target injection system that allows free falling under 1 Hz, using a high repetition laser driver that has been under research and development, as well as the measurement of targets that freely fall. The HAMA laser driver that enabled high repetition fusion experiments is a titanium sapphire laser using a diode-pumped solid-state laser KURE-I of green light output as a driver pump light source. In order to carry out high repetition laser fusion experiments, the target injection device allows free falling of deuterated polystyrene solid sphere targets of 1 mm in diameter under 1 Hz. The authors integrated the developed laser and injection system, and succeeded first in the world in making the nuclear fusion reaction continuously by hitting the target to be injected with laser, which is essential technology for future laser nuclear fusion reactor. In order to realize repetition laser fusion experiments, stable laser, target synchronization control, and target position measurement technologies are indispensable. (A.O.)

  4. High gain direct drive target designs and supporting experiments with KrF

    International Nuclear Information System (INIS)

    Karasik, Max; Bates, Jason W.; Aglitskiy, Yefim

    2013-01-01

    Krypton-fluoride laser is an attractive inertial fusion energy driver from the standpoint of target physics. Target designs taking advantage of zooming, shock ignition, and favorable physics with KrF reach energy gains of 200 with sub-MJ laser energy. The designs are robust under 2D simulations. Experiments on the Nike KrF laser support the physics basis. (author)

  5. Proton and neutron polarized targets for nucleon-nucleon experiments at SATURNE II

    International Nuclear Information System (INIS)

    Ball, J.; Combet, M.; Sans, J.L.; Benda, B.; Chaumette, P.; Deregel, J.; Durand, G.; Dzyubak, A.P.; Gaudron, C.; Lehar, F.; Janout, Z.; Khachaturov, B.A.

    1996-01-01

    A SATURNE polarized target has been used for nucleon-nucleon elastic scattering and transmission experiments for 15 years. The polarized proton target is a 70 cm 3 cartridge loaded with Pentanol-2. For polarized neutron target, two cartridges loaded with 6 LiD and 6 LiH are set in the refrigerator and can be quickly inserted in the beam. First experiments using 6 Li products in quasielastic pp or pn analyzing power measurements are compared with the same observables measured in a free nucleon-nucleon scattering using polarized proton targets. Angular distribution as a function of a kinematically conjugate angle and coplanarity in nucleon-nucleon scattering is shown for different targets. (author)

  6. MEGAPIE, a 1 MW pilot experiment for a liquid metal spallation target

    International Nuclear Information System (INIS)

    Bauer, G.S.; Salvatores, M.; Heusener, G.

    2001-01-01

    MEGAPIE (Megawatt Pilot Target Experiment) is an initiative launched by Commissariat a l'Energie Atomique, Cadarache (France) and Forschungszentrum Karlsruhe (Germany) in collaboration with Paul Scherrer Institut (Switzerland), to demonstrate, in an international collaboration, the feasibility of a liquid lead bismuth target for spallation facilities at a beam power level of 1 MW. Such a target is under consideration for various concepts of accelerator driven systems (ADS) to be used in transmutation of nuclear waste and other applications world-wide. It also has the potential of increasing significantly the thermal neutron flux available at the spallation neutron source (SINQ) for neutron scattering. SINQ's beam power being close to 1 MW already, this facility offers a unique opportunity to realize such an experiment with a reasonably small number of new ancillary systems. The paper describes the basic features of the experiment and its boundary conditions, the technical concept of the target and underlying research carried out at participating laboratories. (author)

  7. Production of direct drive cylindrical targets for inertial confinement fusion experiments

    International Nuclear Information System (INIS)

    Elliott, N.E.; Day, R.D.; Hatch, D.J.; Sandoval, D.L.; Gomez, V.M.; Pierce, T.H.; Elliott, J.E.; Manzanares, R.

    2002-01-01

    We have made targets with cylindrical geometry for Inertial Confinement Fusion (ICF) experiments. These targets are used in hydrodynamic experiments on the OMEGA laser at the University of Rochester. The cylindrical design allows the study of three dimensional hydrodynamic effects in a pseudo 2D mode, simplifying data gathering and analysis. Direct drive refers to the fact that the target is illuminated directly by approximately 50 laser beams and is imploded by the material pressure generated from ablation of the outside of the target. The production of cylindrical targets involves numerous steps. These steps are shared in common with many other types of ICF targets but no other single target type encompasses such a wide range of fabrication techniques. These targets consist of a large number of individual parts, all fabricated from commercially purchased raw material, requiring many machining, assembly, electroplating and chemical process steps. Virtually every manufacturing and assembly process we currently possess is involved in the production of these targets. The generic target consists of a plastic cylinder (ablator) that is roughly lmm in diameter by 2.25mm long. The wall of the cylinder is roughly 0.07mm thick. There is an aluminum cylinder 0.5mm wide and O.Olmm thick centered on the inside of the plastic cylinder and coaxial with the outside plastic cylinder. The outside of this aluminum band has surface finishes of differing random average roughness. The required average surface roughness is determined in advance by experimental design based on the amount of turbulent mix to be observed. The interior of the cylinder is filled with low density polystyrene foam that is made in house. To produce a finished target additional features are added to each target. X-ray backlighters are cantilevered off the target that allow time resolved x-ray images of the imploding target to be recorded during the experiment. The x-ray backlighters are driven by additional

  8. Simultaneous Detection of Human C-Terminal p53 Isoforms by Single Template Molecularly Imprinted Polymers (MIPs) Coupled with Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS)-Based Targeted Proteomics.

    Science.gov (United States)

    Jiang, Wenting; Liu, Liang; Chen, Yun

    2018-03-06

    Abnormal expression of C-terminal p53 isoforms α, β, and γ can cause the development of cancers including breast cancer. To date, much evidence has demonstrated that these isoforms can differentially regulate target genes and modulate their expression. Thus, quantification of individual isoforms may help to link clinical outcome to p53 status and to improve cancer patient treatment. However, there are few studies on accurate determination of p53 isoforms, probably due to sequence homology of these isoforms and also their low abundance. In this study, a targeted proteomics assay combining molecularly imprinted polymers (MIPs) and liquid chromatography-tandem mass spectrometry (LC-MS/MS) was developed for simultaneous quantification of C-terminal p53 isoforms. Isoform-specific surrogate peptides (i.e., KPLDGEYFTLQIR (peptide-α) for isoform α, KPLDGEYFTLQDQTSFQK (peptide-β) for isoform β, and KPLDGEYFTLQMLLDLR (peptide-γ) for isoform γ) were first selected and used in both MIPs enrichment and mass spectrometric detection. The common sequence KPLDGEYFTLQ of these three surrogate peptides was used as single template in MIPs. In addition to optimization of imprinting conditions and characterization of the prepared MIPs, binding affinity and cross-reactivity of the MIPs for each surrogate peptide were also evaluated. As a result, a LOQ of 5 nM was achieved, which was >15-fold more sensitive than that without MIPs. Finally, the assay was validated and applied to simultaneous quantitative analysis of C-terminal p53 isoforms α, β, and γ in several human breast cell lines (i.e., MCF-10A normal cells, MCF-7 and MDA-MB-231 cancer cells, and drug-resistant MCF-7/ADR cancer cells). This study is among the first to employ single template MIPs and cross-reactivity phenomenon to select isoform-specific surrogate peptides and enable simultaneous quantification of protein isoforms in LC-MS/MS-based targeted proteomics.

  9. Gas-filled targets for large scalelength plasma interaction experiments on Nova

    International Nuclear Information System (INIS)

    Powers, L.V.; Berger, R.L.; Munro, D.H.

    1994-11-01

    Stimulated Brillouin backscatter from large scale length gas-filled targets has been measured on Nova. These targets were designed to approximate conditions in indirect drive ignition target designs in underdense plasma electron density (n e ∼10 21 /cm 3 ), temperature (T e >3 keV), and gradient scale lengths (L n ∼ mm, L v >6 mm) as well as calculated gain for stimulated Brillouin scattering (SBS). The targets used in these experiments were gas-filled balloons with polyimide walls (gasbags) and gas-filled hohlraums. Detailed characterization using x-ray imaging and x-ray and optical spectroscopy verifies that the calculated plasma conditions are achieved. Time-resolved SBS backscatter from these targets is <3% for conditions similar to ignition target designs

  10. Mining the granule proteome

    DEFF Research Database (Denmark)

    Albrethsen, Jakob; Goetze, Jens P; Johnsen, Anders H

    2015-01-01

    Proteomics of secretory granules is an emerging strategy for identifying secreted proteins, including potentially novel candidate biomarkers and peptide hormones. In addition, proteomics can provide information about the abundance, localization and structure (post-translational modification) of g...

  11. The Merit(nTOF-11) High Intensity Liquid Mercury Target Experiment at the CERN PS

    CERN Document Server

    Efthymiopoulos, I; Caretta, O; Carroll, A J; Fabich, A; Graves, V B; Grudiev, A; Haug, F; Kirk, H G; Lettry, Jacques; Loveridge, P; McDonald, K T; Mokhov, N; Palm, M; Park, H; Pernegger, H; Spampinato, P T; Steerenberg, R; Striganov, S; Tsang, T

    2008-01-01

    The MERIT(nTOF-11) experiment is a proof-ofprinciple test of a target system for a high power proton beam to be used as front-end for a neutrino factory or a muon collider. The experiment took data in autumn 2007 with the fast-extracted beam from the CERN Proton Synchrotron (PS) to a maximum intensity of $30 × 10^{12}$ per pulse. The target system, based on a free mercury jet, is capable of intercepting a 4-MW proton beam inside a 15-T magnetic field required to capture the low energy secondary pions as the source for intense muon beams. Partice detectors installed around the target setup measure the secondary particle flux out of the target and can probe cavitation effects in the mercury jet when excited by an intense proton beam.Preliminary results of the data analysis will be presented here.

  12. Time Structure of Particle Production in the Merit High-Power Target Experiment

    CERN Document Server

    Efthymiopoulos, I; Palm, M; Lettry, J; Haug, F; Pereira, H; Pernegger, H; Steerenberg, R; Grudiev, A; Kirk, H G; Park, H; Tsang, T; Mokhov, N; Striganov, S; Carroll, A J; Graves, V B; Spampinato, P T; McDonald, K T; Bennett, J R J; Caretta, O; Loveridge, P

    2010-01-01

    The MERIT experiment is a proof-of-principle test of a target system for high power proton beam to be used as front-end for a neutrino factory complex or amuon collider. The experiment took data in autumn 2007 with the fast extracted beam from the CERN Proton Synchrotron (PS) to a maximum intensity of about 30 × 1012 protons per pulse. We report results from the portion of the MERIT experiment in which separated beam pulses were delivered to a free mercury jet target with time intervals between pulses varying from 2 to 700 μs. The analysis is based on the responses of particle detectors placed along side and downstream of the target.

  13. Making proteomics data accessible and reusable: current state of proteomics databases and repositories.

    Science.gov (United States)

    Perez-Riverol, Yasset; Alpi, Emanuele; Wang, Rui; Hermjakob, Henning; Vizcaíno, Juan Antonio

    2015-03-01

    Compared to other data-intensive disciplines such as genomics, public deposition and storage of MS-based proteomics, data are still less developed due to, among other reasons, the inherent complexity of the data and the variety of data types and experimental workflows. In order to address this need, several public repositories for MS proteomics experiments have been developed, each with different purposes in mind. The most established resources are the Global Proteome Machine Database (GPMDB), PeptideAtlas, and the PRIDE database. Additionally, there are other useful (in many cases recently developed) resources such as ProteomicsDB, Mass Spectrometry Interactive Virtual Environment (MassIVE), Chorus, MaxQB, PeptideAtlas SRM Experiment Library (PASSEL), Model Organism Protein Expression Database (MOPED), and the Human Proteinpedia. In addition, the ProteomeXchange consortium has been recently developed to enable better integration of public repositories and the coordinated sharing of proteomics information, maximizing its benefit to the scientific community. Here, we will review each of the major proteomics resources independently and some tools that enable the integration, mining and reuse of the data. We will also discuss some of the major challenges and current pitfalls in the integration and sharing of the data. © 2014 The Authors. PROTEOMICS published by Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  14. Cannonball target experiment with the GEKKO laser system at ILE Osaka

    International Nuclear Information System (INIS)

    Yamanaka, C.; Azechi, H.; Fujiwara, E.

    1985-01-01

    The GEKKO series glass laser systems are now in operation for the Cannonball target experiments. GEKKO XII is a twelve-beam 30 kJ, 50 TW laser provided with two target chambers. Three types of GEKKO lasers cover the UV, blue, green and red frequency ranges. The Cannonball target displays an excellent performance in implosion. Two kinds of Cannonball target are proposed: the plasma Cannonball and the radiation Cannonball. The neutron yield is 4x10 10 , and the DT fuel density attains 10 g.cm -3 . Laser-to-X-ray conversion has been investigated. Cryogenic target implosion has been performed by using a tailored laser pulse to produce the flush at the core. Various kinds of new diagnostics are being developed. (author)

  15. NMR parallel Q-meter with double-balanced-mixer detection for polarized target experiments

    International Nuclear Information System (INIS)

    Boissevain, J.; Tippens, W.B.

    1983-01-01

    A constant-voltage, parallel-tuned nuclear magnetic resonance (NMR) circuit, patterned after a Liverpool design, has been developed for polarized target experiments. Measuring the admittance of the resonance circuit allows advantageous use of double-balanced mixer detection. The resonant circuit is tolerant of stray capacitance between the NMR coil and the target cavity, thus easing target-cell-design constraints. The reference leg of the circuit includes a voltage-controlled attenuator and phase shifter for ease of tuning. The NMR output features a flat background and has good linearity and stability

  16. New Fixed-Target Experiments to Search for Dark Gauge Forces

    Energy Technology Data Exchange (ETDEWEB)

    Bjorken, James D.; Essig, Rouven; Schuster, Philip; /SLAC; Toro, Natalia; /Stanford U., ITP

    2010-06-11

    Fixed-target experiments are ideally suited for discovering new MeV-GeV mass U(1) gauge bosons through their kinetic mixing with the photon. In this paper, we identify the production and decay properties of new light gauge bosons that dictate fixed-target search strategies. We summarize existing limits and suggest five new experimental approaches that we anticipate can cover most of the natural parameter space, using currently operating GeV-energy beams and well-established detection methods. Such experiments are particularly timely in light of recent terrestrial and astrophysical anomalies (PAMELA, FERMI, DAMA/LIBRA, etc.) consistent with dark matter charged under a new gauge force.

  17. The Human Plasma Proteome Draft of 2017: Building on the Human Plasma PeptideAtlas from Mass Spectrometry and Complementary Assays.

    Science.gov (United States)

    Schwenk, Jochen M; Omenn, Gilbert S; Sun, Zhi; Campbell, David S; Baker, Mark S; Overall, Christopher M; Aebersold, Ruedi; Moritz, Robert L; Deutsch, Eric W

    2017-12-01

    Human blood plasma provides a highly accessible window to the proteome of any individual in health and disease. Since its inception in 2002, the Human Proteome Organization's Human Plasma Proteome Project (HPPP) has been promoting advances in the study and understanding of the full protein complement of human plasma and on determining the abundance and modifications of its components. In 2017, we review the history of the HPPP and the advances of human plasma proteomics in general, including several recent achievements. We then present the latest 2017-04 build of Human Plasma PeptideAtlas, which yields ∼43 million peptide-spectrum matches and 122,730 distinct peptide sequences from 178 individual experiments at a 1% protein-level FDR globally across all experiments. Applying the latest Human Proteome Project Data Interpretation Guidelines, we catalog 3509 proteins that have at least two non-nested uniquely mapping peptides of nine amino acids or more and >1300 additional proteins with ambiguous evidence. We apply the same two-peptide guideline to historical PeptideAtlas builds going back to 2006 and examine the progress made in the past ten years in plasma proteome coverage. We also compare the distribution of proteins in historical PeptideAtlas builds in various RNA abundance and cellular localization categories. We then discuss advances in plasma proteomics based on targeted mass spectrometry as well as affinity assays, which during early 2017 target ∼2000 proteins. Finally, we describe considerations about sample handling and study design, concluding with an outlook for future advances in deciphering the human plasma proteome.

  18. LH2 Target Design & Position Survey Techniques for the MUSE experiment for Precise Proton Radius Measurement

    Science.gov (United States)

    Le Pottier, Luc; Roy, Pryiashee; Lorenzon, Wolfgang; Raymond, Richard; Steinberg, Noah; Rossi de La Fuente, Erick; MUSE (MUon proton Scattering Experiment) Collaboration

    2017-09-01

    The proton radius puzzle is a currently unresolved problem which has intrigued the scientific community, dealing with a 7 σ discrepancy between the proton radii determined from muonic hydrogen spectroscopy and electron scattering measurements. The MUon Scattering Experiment (MUSE) aims to resolve this puzzle by performing the first simultaneous elastic scattering measurements of both electrons and muons on the proton, which will allow the comparison of the radii from the two interactions with reduced systematic uncertainties. The data from this experiment is expected to provide the best test of lepton universality to date. The experiment will take place at the Paul Scherrer Institute in Switzerland in 2018. An essential component of the experiment is a liquid hydrogen (LH2) cryotarget system. Our group at the University of Michigan is responsible for the design, fabrication and installation of this system. Here we present our LH2 target cell design and fabrication techniques for successful operation at 20 K and 1 atm, and our computer vision-based target position survey system which will determine the position of the target, installed inside a vacuum chamber, with 0.01 mm or better precision at the height of the liquid hydrogen target and along the beam direction during the experiment.

  19. [Proteomics and transfusion medicine].

    Science.gov (United States)

    Lion, N; Prudent, M; Crettaz, D; Tissot, J-D

    2011-04-01

    The term "proteomics" covers tools and techniques that are used to analyze and characterize complex mixtures of proteins from various biological samples. In this short review, a typical proteomic approach, related to the study of particular and illustrative situation related to transfusion medicine is reported. This "case report" will allow the reader to be familiar with a practical proteomic approach of a real situation, and will permit to describe the tools that are usually used in proteomic labs, and, in a second part, to present various proteomic applications in transfusion medicine. Copyright © 2011 Elsevier Masson SAS. All rights reserved.

  20. PIQMIe: A web server for semi-quantitative proteomics data management and analysis

    NARCIS (Netherlands)

    A. Kuzniar (Arnold); R. Kanaar (Roland)

    2014-01-01

    textabstractWe present the Proteomics Identifications and Quantitations Data Management and Integration Service or PIQMIe that aids in reliable and scalable data management, analysis and visualization of semi-quantitative mass spectrometry based proteomics experiments. PIQMIe readily integrates

  1. The fixed target experiment for studies of baryonic matter at the Nuclotron (BM rate at N)

    Energy Technology Data Exchange (ETDEWEB)

    Kapishin, Mikhail [Joint Institute for Nuclear Research, Dubna, Moscow region (Russian Federation)

    2016-08-15

    BM rate at N (Baryonic Matter at Nuclotron) is the first experiment to be realized at the accelerator complex of NICA-Nuclotron. The aim of the BM rate at N experiment is to study interactions of relativistic heavy-ion beams with fixed targets. The BM rate at N setup, results of Monte Carlo simulations and the BM rate at N experimental program are presented. (orig.)

  2. Annotated Gene and Proteome Data Support Recognition of Interconnections Between the Results of Different Experiments in Space Research

    Science.gov (United States)

    Bauer, Johann; Wehland, Markus; Pietsch, Jessica; Sickmann, Albert; Weber, Gerhard; Grimm, Daniela

    2016-06-01

    In a series of studies, human thyroid and endothelial cells exposed to real or simulated microgravity were analyzed in terms of changes in gene expression patterns or protein content. Due to the limitation of available cells in many space research experiments, comparative and control experiments had to be done in a serial manner. Therefore, detected genes or proteins were annotated with gene names and SwissProt numbers, in order to allow searches for interconnections between results obtained in different experiments by different methods. A crosscheck of several studies on the behavior of cytoskeletal genes and proteins suggested that clusters of cytoskeletal components change differently under the influence of microgravity and/or vibration in different cell types. The result that LOX and ISG15 gene expression were clearly altered during the Shenzhou-8 spaceflight mission could be estimated by comparison with the results of other experiments. The more than 100-fold down-regulation of LOX supports our hypothesis that the amount and stability of extracellular matrix have a great influence on the formation of three-dimensional aggregates under microgravity. The approximately 40-fold up-regulation of ISG15 cannot yet be explained in detail, but strongly suggests that ISGylation, an alternative form of posttranslational modification, plays a role in longterm cultures.

  3. The Jet Experiments in Nuclear Structure and Astrophysics (JENSA) gas jet target

    International Nuclear Information System (INIS)

    Chipps, K.A.; Greife, U.; Bardayan, D.W.; Blackmon, J.C.; Kontos, A.; Linhardt, L.E.; Matos, M.; Pain, S.D.; Pittman, S.T.; Sachs, A.; Schatz, H.; Schmitt, K.T.; Smith, M.S.; Thompson, P.

    2014-01-01

    New radioactive ion beam (RIB) facilities will push further away from stability and enable the next generation of nuclear physics experiments. Of great importance to the future of RIB physics are scattering, transfer, and capture reaction measurements of rare, exotic, and unstable nuclei on light targets such as hydrogen and helium. These measurements require targets that are dense, highly localized, and pure. Targets must also accommodate the use of large area silicon detector arrays, high-efficiency gamma arrays, and heavy ion detector systems to efficiently measure the reaction products. To address these issues, the Jet Experiments in Nuclear Structure and Astrophysics (JENSA) Collaboration has designed, built, and characterized a supersonic gas jet target, capable of providing gas areal densities on par with commonly used solid targets within a region of a few millimeters diameter. Densities of over 5×10 18 atoms/cm 2 of helium have been achieved, making the JENSA gas jet target the most dense helium jet achieved so far

  4. The cryogenic target for the G0 experiment at Jefferson lab

    International Nuclear Information System (INIS)

    Covrig, S.D.; Beise, E.J.; Carr, R.; Gustafsson, K.K.; Hannelius, L.; Herda, M.-C.; Jones, C.E.; Liu, J.; McKeown, R.D.; Neveling, R.; Rauf, A.W.; Smith, G.

    2005-01-01

    A cryogenic horizontal single loop target has been designed, built, tested and operated for the G 0 experiment in Hall C at Jefferson Lab. The target cell is 20cm long, the loop volume is 6.5l and the target operates with the cryogenic pump fully immersed in the fluid. The target has been designed to operate at 30Hz rotational pump speed with either liquid hydrogen or liquid deuterium. The high-power heat exchanger is able to remove 1000W of heat from the liquid hydrogen, while the nominal electron beam with current of 40μA and energy of 3GeV deposits about 320W of heat into the liquid. The increase in the systematic uncertainty due to the liquid hydrogen target is negligible on the scale of a parity violation experiment. The global normalized yield reduction for 40μA beam is about 1.5% and the target density fluctuations contribute less than 238ppm (parts per million) to the total asymmetry width, typically about 1200ppm, in a Q 2 bin

  5. Proteogenomics Dashboard for the Human Proteome Project.

    Science.gov (United States)

    Tabas-Madrid, Daniel; Alves-Cruzeiro, Joao; Segura, Victor; Guruceaga, Elizabeth; Vialas, Vital; Prieto, Gorka; García, Carlos; Corrales, Fernando J; Albar, Juan Pablo; Pascual-Montano, Alberto

    2015-09-04

    dasHPPboard is a novel proteomics-based dashboard that collects and reports the experiments produced by the Spanish Human Proteome Project consortium (SpHPP) and aims to help HPP to map the entire human proteome. We have followed the strategy of analog genomics projects like the Encyclopedia of DNA Elements (ENCODE), which provides a vast amount of data on human cell lines experiments. The dashboard includes results of shotgun and selected reaction monitoring proteomics experiments, post-translational modifications information, as well as proteogenomics studies. We have also processed the transcriptomics data from the ENCODE and Human Body Map (HBM) projects for the identification of specific gene expression patterns in different cell lines and tissues, taking special interest in those genes having little proteomic evidence available (missing proteins). Peptide databases have been built using single nucleotide variants and novel junctions derived from RNA-Seq data that can be used in search engines for sample-specific protein identifications on the same cell lines or tissues. The dasHPPboard has been designed as a tool that can be used to share and visualize a combination of proteomic and transcriptomic data, providing at the same time easy access to resources for proteogenomics analyses. The dasHPPboard can be freely accessed at: http://sphppdashboard.cnb.csic.es.

  6. Evidence for reduction of turbulent mixing at the ablation front in experiments with shell targets

    International Nuclear Information System (INIS)

    Lykov, V.A.; Avrorin, E.N.; Karlykhanov, N.G.; Murashkina, V.A.; Myalitsin, L.A.; Neuvazhaev, V.E.; Pasyukova, A.F.; Yakovlev, V.G.

    1994-01-01

    The results of the computation analysis of the turbulent mixing in the direct and indirect-driven shell targets are presented. The simulation were carried out by TURLINA-code based on phenomenological mixing model. The effects of the mixing are studied numerically for the SOKOL-laser experiments and for the indirect-driven targets. The comparison of the TURLINA-code simulations with the SOKOL experimental X-ray picture gives the evidence for reduction of turbulent mixing at the ablation front in experiments with shell targets. The estimates of the initial roughness and the effect of ablation-stabilization influence on the turbulent mixing and neutron yield from DT-filled glass microballoon are carried out. The allowable compression asymmetry for thermonuclear ignition is discussed. copyright 1994 American Institute of Physics

  7. Proteomics of Plant Pathogenic Fungi

    Directory of Open Access Journals (Sweden)

    Raquel González-Fernández

    2010-01-01

    Full Text Available Plant pathogenic fungi cause important yield losses in crops. In order to develop efficient and environmental friendly crop protection strategies, molecular studies of the fungal biological cycle, virulence factors, and interaction with its host are necessary. For that reason, several approaches have been performed using both classical genetic, cell biology, and biochemistry and the modern, holistic, and high-throughput, omic techniques. This work briefly overviews the tools available for studying Plant Pathogenic Fungi and is amply focused on MS-based Proteomics analysis, based on original papers published up to December 2009. At a methodological level, different steps in a proteomic workflow experiment are discussed. Separate sections are devoted to fungal descriptive (intracellular, subcellular, extracellular and differential expression proteomics and interactomics. From the work published we can conclude that Proteomics, in combination with other techniques, constitutes a powerful tool for providing important information about pathogenicity and virulence factors, thus opening up new possibilities for crop disease diagnosis and crop protection.

  8. Proteomic interrogation of human chromatin.

    Directory of Open Access Journals (Sweden)

    Mariana P Torrente

    Full Text Available Chromatin proteins provide a scaffold for DNA packaging and a basis for epigenetic regulation and genomic maintenance. Despite understanding its functional roles, mapping the chromatin proteome (i.e. the "Chromatome" is still a continuing process. Here, we assess the biological specificity and proteomic extent of three distinct chromatin preparations by identifying proteins in selected chromatin-enriched fractions using mass spectrometry-based proteomics. These experiments allowed us to produce a chromatin catalog, including several proteins ranging from highly abundant histone proteins to less abundant members of different chromatin machinery complexes. Using a Normalized Spectral Abundance Factor approach, we quantified relative abundances of the proteins across the chromatin enriched fractions giving a glimpse into their chromosomal abundance. The large-scale data sets also allowed for the discovery of a variety of novel post-translational modifications on the identified chromatin proteins. With these comparisons, we find one of the probed methods to be qualitatively superior in specificity for chromatin proteins, but inferior in proteomic extent, evidencing a compromise that must be made between biological specificity and broadness of characterization. Additionally, we attempt to identify proteins in eu- and heterochromatin, verifying the enrichments by characterizing the post-translational modifications detected on histone proteins from these chromatin regions. In summary, our results provide insights into the value of different methods to extract chromatin-associated proteins and provide starting points to study the factors that may be involved in directing gene expression and other chromatin-related processes.

  9. Construction and performance of a plastic scintillating fiber target for a rare kaon decay experiment

    International Nuclear Information System (INIS)

    Frank, J.S.; Strand, R.C.

    1988-01-01

    A K + stopping target consisting of 2269 plastic fibers, 2 mm diameter and 3.12 m long has been installed in an experiment searching for the rare decay K + to πν/bar nu/ at Brookhaven National Laboratory. The fibers are bundled onto 379 photomultiplier tube and base assemblies with single photoelectron resolution. After routing to the counting room, the signals are amplified and then distributed to TDC's and high-pass filter circuits that provide signals to ADC's and to fan-ins that provide a target energy-sum pulse used in the fast triggering logic. A minimum ionizing particle 3 m from the photomultiplier yields 1 photoelectron/mm path. The target provides transverse spatial resolution of 4 mm (FWHM) for the vertex of the K + decay and 2 ns timing resolution (FWHM) on the difference between the K + stop and the subsequent decay. Details of the target construction and operating performance are provided. 4 refs., 7 figs

  10. Pripper: prediction of caspase cleavage sites from whole proteomes

    Directory of Open Access Journals (Sweden)

    Salmi Jussi

    2010-06-01

    Full Text Available Abstract Background Caspases are a family of proteases that have central functions in programmed cell death (apoptosis and inflammation. Caspases mediate their effects through aspartate-specific cleavage of their target proteins, and at present almost 400 caspase substrates are known. There are several methods developed to predict caspase cleavage sites from individual proteins, but currently none of them can be used to predict caspase cleavage sites from multiple proteins or entire proteomes, or to use several classifiers in combination. The possibility to create a database from predicted caspase cleavage products for the whole genome could significantly aid in identifying novel caspase targets from tandem mass spectrometry based proteomic experiments. Results Three different pattern recognition classifiers were developed for predicting caspase cleavage sites from protein sequences. Evaluation of the classifiers with quality measures indicated that all of the three classifiers performed well in predicting caspase cleavage sites, and when combining different classifiers the accuracy increased further. A new tool, Pripper, was developed to utilize the classifiers and predict the caspase cut sites from an arbitrary number of input sequences. A database was constructed with the developed tool, and it was used to identify caspase target proteins from tandem mass spectrometry data from two different proteomic experiments. Both known caspase cleavage products as well as novel cleavage products were identified using the database demonstrating the usefulness of the tool. Pripper is not restricted to predicting only caspase cut sites, but it gives the possibility to scan protein sequences for any given motif(s and predict cut sites once a suitable cut site prediction model for any other protease has been developed. Pripper is freely available and can be downloaded from http://users.utu.fi/mijopi/Pripper. Conclusions We have developed Pripper, a tool for

  11. Mitochondrial-targeted aryl hydrocarbon receptor and the impact of 2,3,7,8-tetrachlorodibenzo-p-dioxin on cellular respiration and the mitochondrial proteome

    Energy Technology Data Exchange (ETDEWEB)

    Hwang, Hye Jin [Department of Biochemistry and Molecular Biology, Michigan State University, East Lansing, MI 48824 (United States); Center for Mitochondrial Science and Medicine, Michigan State University, East Lansing, MI 48824 (United States); Dornbos, Peter [Department of Biochemistry and Molecular Biology, Michigan State University, East Lansing, MI 48824 (United States); Institute for Integrative Toxicology, Michigan State University, East Lansing, MI 48824-1319 (United States); Steidemann, Michelle [Institute for Integrative Toxicology, Michigan State University, East Lansing, MI 48824-1319 (United States); Department of Pharmacology and Toxicology, Michigan State University, East Lansing, MI 48824 (United States); Dunivin, Taylor K. [Department of Microbiology and Molecular Genetics, Michigan State University, East Lansing, MI 48824 (United States); Rizzo, Mike [Institute for Integrative Toxicology, Michigan State University, East Lansing, MI 48824-1319 (United States); Cell and Molecular Biology Graduate Program, Michigan State University, East Lansing, MI 48824 (United States); LaPres, John J., E-mail: lapres@msu.edu [Department of Biochemistry and Molecular Biology, Michigan State University, East Lansing, MI 48824 (United States); Center for Mitochondrial Science and Medicine, Michigan State University, East Lansing, MI 48824 (United States)

    2016-08-01

    The aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor within the Per-Arnt-Sim (PAS) domain superfamily. Exposure to the most potent AHR ligand, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), is associated with various pathological effects including metabolic syndrome. While research over the last several years has demonstrated a role for oxidative stress and metabolic dysfunction in AHR-dependent TCDD-induced toxicity, the role of the mitochondria in this process has not been fully explored. Our previous research suggested that a portion of the cellular pool of AHR could be found in the mitochondria (mitoAHR). Using a protease protection assay with digitonin extraction, we have now shown that this mitoAHR is localized to the inter-membrane space (IMS) of the organelle. TCDD exposure induced a degradation of mitoAHR similar to that of cytosolic AHR. Furthermore, siRNA-mediated knockdown revealed that translocase of outer-mitochondrial membrane 20 (TOMM20) was involved in the import of AHR into the mitochondria. In addition, TCDD altered cellular respiration in an AHR-dependent manner to maintain respiratory efficiency as measured by oxygen consumption rate (OCR). Stable isotope labeling by amino acids in cell culture (SILAC) identified a battery of proteins within the mitochondrial proteome influenced by TCDD in an AHR-dependent manner. Among these, 17 proteins with fold changes ≥ 2 are associated with various metabolic pathways, suggesting a role of mitochondrial retrograde signaling in TCDD-mediated pathologies. Collectively, these studies suggest that mitoAHR is localized to the IMS and AHR-dependent TCDD-induced toxicity, including metabolic dysfunction, wasting syndrome, and hepatic steatosis, involves mitochondrial dysfunction. - Highlights: • The mitoAHR is localized in the mitochondrial intermembrane space. • TOMM20 participates in mitoAHR translocation. • AHR contributes to the maintenance of respiratory control ratio following

  12. Efficient and robust identification of cortical targets in concurrent TMS-fMRI experiments

    Science.gov (United States)

    Yau, Jeffrey M.; Hua, Jun; Liao, Diana A.; Desmond, John E.

    2014-01-01

    Transcranial magnetic stimulation (TMS) can be delivered during fMRI scans to evoke BOLD responses in distributed brain networks. While concurrent TMS-fMRI offers a potentially powerful tool for non-invasively investigating functional human neuroanatomy, the technique is currently limited by the lack of methods to rapidly and precisely localize targeted brain regions – a reliable procedure is necessary for validly relating stimulation targets to BOLD activation patterns, especially for cortical targets outside of motor and visual regions. Here we describe a convenient and practical method for visualizing coil position (in the scanner) and identifying the cortical location of TMS targets without requiring any calibration or any particular coil-mounting device. We quantified the precision and reliability of the target position estimates by testing the marker processing procedure on data from 9 scan sessions: Rigorous testing of the localization procedure revealed minimal variability in coil and target position estimates. We validated the marker processing procedure in concurrent TMS-fMRI experiments characterizing motor network connectivity. Together, these results indicate that our efficient method accurately and reliably identifies TMS targets in the MR scanner, which can be useful during scan sessions for optimizing coil placement and also for post-scan outlier identification. Notably, this method can be used generally to identify the position and orientation of MR-compatible hardware placed near the head in the MR scanner. PMID:23507384

  13. A Biotin Switch-Based Proteomics Approach Identifies 14-3-3ζ as a Target of Sirt1 in the Metabolic Regulation of Caspase-2

    Science.gov (United States)

    Andersen, Joshua L.; Thompson, J. Will; Lindblom, Kelly R.; Johnson, Erika S.; Yang, Chih-Sheng; Lilley, Lauren R.; Freel, Christopher D.; Moseley, M. Arthur; Kornbluth, Sally

    2011-01-01

    While lysine acetylation in the nucleus is well characterized, comparatively little is known about its significance in cytoplasmic signaling. Here we show that inhibition of the Sirt1 deacetylase, which is primarily cytoplasmic in cancer cell lines, sensitizes these cells to caspase-2-dependent death. To identify relevant Sirt1 substrates, we developed a novel proteomics strategy, enabling the identification of a range of putative substrates, including 14-3-3ζ, a known direct regulator of caspase-2. We show here that inhibition of Sirtuin activity accelerates caspase activation and overrides caspase-2 suppression by nutrient abundance. Furthermore, 14-3-3ζ is acetylated prior to caspase activation, and supplementation of Xenopus egg extract with glucose-6-phosphate, which promotes caspase-2/14-3-3ζ binding, enhances 14-3-3ζ-directed Sirtuin activity. Conversely, inhibiting Sirtuin activity promotes 14-3-3ζ dissociation from caspase-2 in both egg extract and human cell lines. These data reveal a role for Sirt1 in modulating apoptotic sensitivity, in response to metabolic changes, by antagonizing 14-3-3ζ acetylation. PMID:21884983

  14. MERIT - The high intensity liquid mercury target experiment at the CERN PS

    CERN Document Server

    Efthymiopoulos, I

    2009-01-01

    The MERIT experiment is a proof-of-principle test of a target system for high power proton beams to be used as front-end for a Neutrino Factory complex or a Muon Collider. The experiment took data in autumn 2007 with the fast extracted beam from the CERN Proton Synchrotron (PS) to a maximum intensity of about 30 × 1012 protons per pulse. The target system, based on a free mercury jet, allowed investigation of the interseption of a 4-MW proton beam inside a 15-T magnetic field required to capture the low-energy secondary pions as the source of the required intense muon beams. Particle detectors have been installed around the target setup to measure the secondary particle flux out of the target and probe cavitation effects in the mercury jet when exited with a beam of variable intensity. With the analysis of the data ongoing, results will be presented here that demonstrate the validity of the liquid target concept.

  15. Performance of a Liner-on-Target Injector for Staged Z-Pinch Experiments

    Science.gov (United States)

    Conti, F.; Valenzuela, J. C.; Narkis, J.; Krasheninnikov, I.; Beg, F.; Wessel, F. J.; Ruskov, E.; Rahman, H. U.; McGee, E.

    2016-10-01

    We present the design and characterization of a compact liner-on-target injector, used in the Staged Z-pinch experiments conducted on the UNR-NTF Zebra Facility. Previous experiments and analysis indicate that high-Z gas liners produce a uniform and efficient implosion on a low-Z target plasma. The liner gas shell is produced by an annular solenoid valve and a converging-diverging nozzle designed to achieve a collimated, supersonic, Mach-5 flow. The on-axis target is produced by a coaxial plasma gun, where a high voltage pulse is applied to ionize neutral gas and accelerate the plasma by the J-> × B-> force. Measurements of the liner and target dynamics, resolved by interferometry in space and time, fast imaging, and collection of the emitted light, are presented. The results are compared to the predictions from Computational Fluid Dynamics and MHD simulations that model the injector. Optimization of the design parameters, for upcoming Staged Z-pinch experiments, will be discussed. Advanced Research Projects Agency - Energy, DE-AR0000569.

  16. MEGAPIE, a 1 MW pilot experiment for a liquid metal spallation target

    Energy Technology Data Exchange (ETDEWEB)

    Bauer, G.S. [Paul Scherrer Institut, Spallation Neutron Source Division, Villigen-PSI (Switzerland); Salvatores, M. [CEA Cadarache, Direction des Reacteurs Nucleaires, Saint-Paul-lez-Durance Cedex (France); Heusener, G. [Forschungszentrum Karlsruhe, Projekt Nukleare Sicherheitsforschung, Karlsruhe (Germany)

    2001-03-01

    MEGAPIE (Megawatt Pilot Target Experiment) is an initiative launched by Commissariat a l'Energie Atomique, Cadarache (France) and Forschungszentrum Karlsruhe (Germany) in collaboration with Paul Scherrer Institut (Switzerland), to demonstrate, in an international collaboration, the feasibility of a liquid lead bismuth target for spallation facilities at a beam power level of 1 MW. Such a target is under consideration for various concepts of accelerator driven systems (ADS) to be used in transmutation of nuclear waste and other applications world-wide. It also has the potential of increasing significantly the thermal neutron flux available at the spallation neutron source (SINQ) for neutron scattering. SINQ's beam power being close to 1 MW already, this facility offers a unique opportunity to realize such an experiment with a reasonably small number of new ancillary systems. The paper describes the basic features of the experiment and its boundary conditions, the technical concept of the target and underlying research carried out at participating laboratories. (author)

  17. A T0/Trigger detector for the External Target Experiment at CSR

    Science.gov (United States)

    Hu, D.; Shao, M.; Sun, Y.; Li, C.; Chen, H.; Tang, Z.; Zhang, Y.; Zhou, J.; Zeng, H.; Zhao, X.; You, W.; Song, G.; Deng, P.; Lu, J.; Zhao, L.

    2017-06-01

    A new T0/Trigger detector based on multi-gap resistive plate chamber (MRPC) technology has been constructed and tested for the external target experiment (ETE) at HIRFL-CSR. It measures the multiplicity and timing information of particles produced in heavy-ion collisions at the target region, providing necessary event collision time (T0) and collision centrality with high precision. Monte-Carlo simulation shows a time resolution of several tens of picosecond can be achieved at central collisions. The experimental tests have been performed for this prototype detector at the CSR-ETE. The preliminary results are shown to demonstrate the performance of the T0/Trigger detector.

  18. All-optical atom trap as a target for MOTRIMS-like collision experiments

    Science.gov (United States)

    Sharma, S.; Acharya, B. P.; De Silva, A. H. N. C.; Parris, N. W.; Ramsey, B. J.; Romans, K. L.; Dorn, A.; de Jesus, V. L. B.; Fischer, D.

    2018-04-01

    Momentum-resolved scattering experiments with laser-cooled atomic targets have been performed since almost two decades with magneto-optical trap recoil ion momentum spectroscopy (MOTRIMS) setups. Compared to experiments with gas-jet targets, MOTRIMS features significantly lower target temperatures allowing for an excellent recoil ion momentum resolution. However, the coincident and momentum-resolved detection of electrons was long rendered impossible due to incompatible magnetic field requirements. Here we report on an experimental approach which is based on an all-optical 6Li atom trap that—in contrast to magneto-optical traps—does not require magnetic field gradients in the trapping region. Atom temperatures of about 2 mK and number densities up to 109 cm-3 make this trap ideally suited for momentum-resolved electron-ion coincidence experiments. The overall configuration of the trap is very similar to conventional magneto-optical traps. It mainly requires small modifications of laser beam geometries and polarization which makes it easily implementable in other existing MOTRIMS experiments.

  19. Recent Developments in Fabrication of Direct Drive Cylinder Targets for Hydrodynamics Experiments at the OMEGA Laser

    International Nuclear Information System (INIS)

    Nobile, A.; Balkey, M.M.; Bartos, J.J.; Batha, S.H.; Day, R.D.; Elliott, J.E.; Elliott, N.E.; Gomez, V.M.; Hatch, D.J.; Lanier, N.E.; Fincke, J.R.; Manzanares, R.; Pierce, T.H.; Sandoval, D.L.; Schmidt, D.W.; Steckle, W.P.

    2004-01-01

    Experimental campaigns are being conducted at the 60 beam OMEGA laser at the University of Rochester's Laboratory for Laser Energetics to acquire data to validate hydrodynamic models in the high energy-density regime. This paper describes targets that have been developed and constructed for these experimental campaigns. Targets are 860 μm inner diameter by 2.2 mm length cylinders with 70 μm thick polymer ablator. On the ablator inner surface and located halfway along the axis of the cylinder is a 500 μm wide Al marker band. Band thicknesses in the range 8-16 microns are used. CH foam with densities in the range 30-90 mg/cc fills the inside of the cylinder. While these targets have been fabricated for years, several new improvements and features have recently been developed. Improvements include the use of epoxy instead of polystyrene for the ablator, and the use of electrodeposited Al for the marker band. A critical feature of the target is the surface feature that is placed on the marker band. Experiments are aimed at understanding the hydrodynamic behavior of imploding cylinders as a function of this surface feature. Recent development work has focused on production of engineered surface features on the target marker band. Using a fast tool servo on a diamond turning lathe, a wide range of specified surface features have been produced. This paper will address improvements to the cylinder targets as well as current development efforts

  20. A Probabilistic Framework for Peptide and Protein Quantification from Data-Dependent and Data-Independent LC-MS Proteomics Experiments

    DEFF Research Database (Denmark)

    Richardson, Katherine; Denny, R.; Hughes, C.

    2012-01-01

    A probability-based quantification framework is presented for the calculation of relative peptide and protein abundance in label-free and label-dependent LC-MS proteomics data. The results are accompanied by credible intervals and regulation probabilities. The algorithm takes into account data un...

  1. A thin gold coated hydrogen heat pipe -cryogenic target for external experiments at cosy

    International Nuclear Information System (INIS)

    Abdel-Bary, M.; Abdel-Samad, S.; Elawadi, G.A.; Kilian, K.; Ritman, J.

    2008-01-01

    A gravity assisted Gold Coated Heat Pipe (GCHP) with 5-mm diameter has been developed and tested to cool a liquid hydrogen target for external beam experiments at COSY. The need for a narrow target diameter leads us to study the effect of reducing the heat pipe diameter to 5 mm instead of 7 mm, to study the effect of coating the external surface of the heat pipe by a polished gold layer (to decrease the radiation heat load), and to study the effect of using the heat pipe without using 20 layers super isolation around it (aluminized Mylar foil) to keep the target diameter as small as possible. The developed gold coated heat pipe was tested with 20 layers of super isolation and without. The operating characteristics for both conditions were compared to show the advantages and disadvantages

  2. A thin gold coated hydrogen heat pipe-cryogenic target for external experiments at COSY

    Science.gov (United States)

    Abdel-Bary, M.; Abdel-Samad, S.; Elawadi, G. A.; Kilian, K.; Ritman, J.

    2009-05-01

    A gravity assisted Gold coated heat pipe (GCHP) with 5-mm diameter has been developed and tested to cool a liquid hydrogen target for external beam experiments at COSY. The need for a narrow target diameter leads us to study the effect of reducing the heat pipe diameter to 5 mm instead of 7 mm, to study the effect of coating the external surface of the heat pipe by a shiny gold layer (to decrease the radiation heat load), and to study the effect of using the heat pipe without using 20 layers of' super-insulation around it (aluminized Mylar foil) to keep the target diameter as small as possible. The developed gold coated heat pipe was tested with 20 layers of super-insulation (WI) and without super-insulation (WOI). The operating characteristics for both conditions were compared to show the advantages and disadvantages.

  3. Manufacturing of calcium, lithium and molybdenum targets for use in nuclear physics experiments

    Science.gov (United States)

    Kheswa, N. Y.; Papka, P.; Buthelezi, E. Z.; Lieder, R. M.; Neveling, R.; Newman, R. T.

    2010-02-01

    This paper describes methods used in the manufacturing of chemically reactive targets such as calcium ( natCa), lithium-6 ( 6Li) and molybdenum-97 ( 97Mo) for nuclear physics experiments at the iThemba LABS cyclotron facility (Faure, South Africa). Due to the chemical properties of these materials a suitable and controlled environment was established in order to minimize oxygen contamination of targets. Calcium was prepared by means of vacuum evaporation while lithium was cold rolled to a desired thickness. In the case of molybdenum, the metallic powder was melted under vacuum using an e-gun followed by cold rolling of the metal bead to a desired thickness. In addition, latest developments toward the establishment of a dedicated nuclear physics target laboratory are discussed.

  4. Manufacturing of calcium, lithium and molybdenum targets for use in nuclear physics experiments

    Energy Technology Data Exchange (ETDEWEB)

    Kheswa, N.Y., E-mail: kheswa@tlabs.ac.z [iThemba Laboratory for Accelerator Based Science, P.O. Box 722, Somerset West 7129, Western Cape (South Africa); Papka, P.; Buthelezi, E.Z.; Lieder, R.M.; Neveling, R.; Newman, R.T. [iThemba Laboratory for Accelerator Based Science, P.O. Box 722, Somerset West 7129, Western Cape (South Africa)

    2010-02-11

    This paper describes methods used in the manufacturing of chemically reactive targets such as calcium ({sup nat}Ca), lithium-6 ({sup 6}Li) and molybdenum-97 ({sup 97}Mo) for nuclear physics experiments at the iThemba LABS cyclotron facility (Faure, South Africa). Due to the chemical properties of these materials a suitable and controlled environment was established in order to minimize oxygen contamination of targets. Calcium was prepared by means of vacuum evaporation while lithium was cold rolled to a desired thickness. In the case of molybdenum, the metallic powder was melted under vacuum using an e-gun followed by cold rolling of the metal bead to a desired thickness. In addition, latest developments toward the establishment of a dedicated nuclear physics target laboratory are discussed.

  5. [Methods of quantitative proteomics].

    Science.gov (United States)

    Kopylov, A T; Zgoda, V G

    2007-01-01

    In modern science proteomic analysis is inseparable from other fields of systemic biology. Possessing huge resources quantitative proteomics operates colossal information on molecular mechanisms of life. Advances in proteomics help researchers to solve complex problems of cell signaling, posttranslational modification, structure and functional homology of proteins, molecular diagnostics etc. More than 40 various methods have been developed in proteomics for quantitative analysis of proteins. Although each method is unique and has certain advantages and disadvantages all these use various isotope labels (tags). In this review we will consider the most popular and effective methods employing both chemical modifications of proteins and also metabolic and enzymatic methods of isotope labeling.

  6. A transition radiation detector interleaved with low-density targets for the NOE experiment

    CERN Document Server

    Alexandrov, K V; Bernardini, P; Brigida, M; Campana, D; Candela, A M; Caruso, R; Cassese, F; Ceres, A; D'Aquino, B; De Cataldo, G; De Mitri, I; Di Credico, A; Favuzzi, C; Fusco, P; Gargano, F; Giglietto, N; Giordano, F; Grillo, A; Guarino, F; Gustavino, C; Lamanna, E; Lauro, A; Leone, A; Loparco, F; Mancarella, G; Martello, D; Mazziotta, M N; Mikheyev, S P; Mongelli, M; Osteria, G; Palladino, Vittorio; Passeggio, G; Perchiazzi, M; Pontoniere, G; Rainó, A; Rocco, R; Romanucci, E; Rubizzo, U; Sacchetti, A; Scapparone, E; Spinelli, P; Tikhomirov, V; Vaccina, A; Vanzanella, E; Weber, M

    2001-01-01

    The NOE Collaboration has proposed a transition radiation detector (TRD) interleaved with marble targets to tag the electron decay channel of tau leptons produced by nu /sub tau /, eventually originated by nu /sub mu / oscillations in a long base line experiment. A reduced scale TRD detector prototype has been built and exposed to an electron/pion beam at the CERN PS. Discrimination capabilities between electrons and both charged and neutral pions, representing the main source of background for our measurement, have been determined obtaining rejection factors of the order of the tenth of percent for charged pions, and of a few percent for the neutral pion, matching the experiment requirements. The capabilities of this detector to measure the energy released by particles that start showering inside the targets are shown. A momentum resolution sigma /sub p//P

  7. Integrated Laser-Target Interaction Experiments on the RAL Petawatt Laser

    International Nuclear Information System (INIS)

    Patel, P. K.; Key, M. H.; Mackinnon, A. J.; Akli, K.; Berry, R.; Borghesi, M.; Brummit, P. A.; Chambers, D.; Clarke, R. J.; Damian, C.; Chen, H.; Eagleton, R.; Freeman, R.; Glenzer, S.; Gregori, G.; Heathcote, R.; Izumi, N.; Kar, S.; King, J. A.; Kock, J.; Kuba, J.; May, M.; Moon, S.; Neely, D.; Neville, D. R.; Nikroo, A.; Niles, A.; Pasley, J.; Patel, N.; Park, H. S.; Romagnani, L.; Shepherd, R.; Snavely, R. A.; Stephens, R.; Stoeckl, C.; Storm, M.; Theobald, W.; Van Maren, R.; Wilks, S. C.; Zhang, B.

    2005-01-01

    We report on two recent experimental campaigns performed on the new Petawatt laser at the Rutherford Appleton Laboratory in the UK.The laser has recently demonstrated performance characteristics of 400 J of laser energy being delivered on target in a sub 400 fs pulse, reaching a peak focal intensity on the order of 10''21 W/cm''2. The experiments covered multiplic areas of investigation including hot electron transport in planar foil and cone focus geometries, relativistic laser-solid interactions proton beam focusing and heating, and high energy K-alpha production and radiography. A somewhat novel approach was taken to the experiments in that all of the diagnostics required for the different areas of study were fielded simultaneously and operated on all shots. Thus, we were able to obtain extensive sets of measurements on a single-shot basis which provides significant benefit to our understanding of the laser-target interaction conditions and plasma properties. (Author)

  8. The Development of a Framework for Target Diagnostic Centralized Control System (TDCCS) in ICF Experiments

    International Nuclear Information System (INIS)

    Zhang Chi; Wang Jian; Yu Xiaoqi; Yang Dong

    2008-01-01

    A framework for target diagnostic centralized control system (TDCCS) in inertial confinement fusion (ICF) experiment has been developed. The developed framework is based on the common object request broker architecture (CORBA) standard and part of the concept from the ICFRoot (a framework based on ROOT for ICF experiments) framework design. This framework is of a component architecture, including a message bus, command executer, status processor, parser and proxy. To test the function of the framework, a simplified prototype of the TDCCS has been developed as well.

  9. Electron cooling application for luminosity preservation in an experiment with internal targets at COSY

    CERN Document Server

    Meshkov, I N; Maier, R; Prasuhn, D; Sidorin, A O; Smirnov, A V; Stein, H J; Stockhorst, H; Trubnikov, G V

    2003-01-01

    This report is an investigation of the beam parameter evolution in the experiments with internal target. In calculations of the proton and deuteron beams we concentrated on cluster, atomic beam, storage cell and pellet targets at ANKE experiment mainly. In these calculations electron and stochastic cooling, intrabeam scattering, scattering on the target and residual gas atoms are taken into account. Beam parameter evolution is investigated in the long-term time scale, up to one hour, at different beam energies in the range from 1.0 to 2.7 GeV for proton beam and from 1 to 2.11 GeV for deuteron beam. The results of numerical simulations of the proton and deuteron beam parameters at different energies obtained using new version of BETACOOL program (elaborated at the first stage of this work [1]) are presented. Optimum parameters of the electron cooling system are estimated. The COSY experiment requirements can be satisfied even when electron cooling time is rather long. That allows to apply an electron cooling ...

  10. Design Optimisation of a High Intensity Beam Facility and Feasibility Experiment of a Solid Fragmented Target

    CERN Document Server

    Charitonidis, Nikolaos; Rivkin, Leonid

    2014-06-13

    The present PhD thesis describes the design, execution and results of the HRMT-10 experiment performed at the HiRadMat facility of the CERN/SPS complex. The first part of the thesis covers the design optimization studies of the HiRadMat facility, focusing in particular on the radiation protection issues. A detailed Monte-Carlo model of the facility has been developed and validated through comparison with measurements. A very satisfactory agreement between the simulation and the experimental data is observed. In the second part of this thesis, a novel feasibility experiment of a fragmented solid target for a future Neutrino Factory or a Super Beam facility, able to support high beam powers ( 1 MW) is presented in detail. A solid granular target has been proposed as an interesting alternative to an open Hg jet target, presently considered as the baseline for such facilities, but posing considerable technical challenges. The HRMT-10 experiment seeks to address the lack of experimental data of the feasibility of...

  11. High pressure deuterium-tritium gas target vessels for muon-catalyzed fusion experiments

    International Nuclear Information System (INIS)

    Caffrey, A.J.; Spaletta, H.W.; Ware, A.G.; Zabriskie, J.M.; Hardwick, D.A.; Maltrud, H.R.; Paciotti, M.A.

    1989-01-01

    In experimental studies of muon-catalyzed fusion, the density of the hydrogen gas mixture is an important parameter. Catalysis of up to 150 fusions per muon has been observed in deuterium-tritium gas mixtures at liquid hydrogen density; at room temperature, such densities require a target gas pressure of the order of 1000 atmospheres (100 MPa, 15,000 psi). We report here the design considerations for hydrogen gas target vessels for muon-catalyzed fusion experiments that operate at 1000 and 10,000 atmospheres. The 1000 atmosphere high pressure target vessels are fabricated of Type A-286 stainless steel and lined with oxygen-free, high-conductivity (OFHC) copper to provide a barrier to hydrogen permeation of the stainless steel. The 10,000 atmosphere ultrahigh pressure target vessels are made from 18Ni (200 grade) maraging steel and are lined with OFHC copper, again to prevent hydrogen permeation of the steel. In addition to target design features, operating requirements, fabrication procedures, and secondary containment are discussed. 13 refs., 3 figs., 1 tab

  12. Optimization of the target system for the hypernuclear experiment at PANDA

    Energy Technology Data Exchange (ETDEWEB)

    Bleser, Sebastian; Sanchez Lorente, Alicia; Steinen, Marcell [Helmholtz-Institut Mainz (Germany); Iazzi, Felice [Politecnico, Torino (Italy); INFN, Torino (Italy); Pochodzalla, Josef; Rittgen, Kai; Sahin, Cihan [Institut fuer Kernphysik, Johannes Gutenberg-Universitaet, Mainz (Germany)

    2014-07-01

    Gamma spectroscopy of double Λ hypernuclei will be one of the main topics addressed by the PANDA experiment at the planned FAIR-facility at Darmstadt, Germany. For this project a dedicated hypernuclear detector setup will be installed. In addition to the general purpose of the PANDA detector it consists of a primary nuclear target for the production of Ξ{sup -} + anti Ξ pairs, a secondary active target for the formation of hypernuclei and the identification of associated decay products as well as a germanium detector array to perform γ spectroscopy. Results of the current hardware development will be presented in the talk: For the positioning of the primary filament target in the beam halo the functionality of piezo motors is investigated in vacuum. Stability tests of the primary target chamber are performed with various thin materials. For the secondary target the readout of silicon microstrip detectors with ultra-thin flexible cables is checked to fan out the readout electronics. Furthermore, design studies of support structures for the whole detector setup are considered. On the simulation side a compromise between the stopping probability of Ξ{sup -} hyperons and the reconstruction accuracy of weak decay pions is discussed.

  13. The Path to Enlightenment: Making Sense of Genomic and Proteomic Information

    OpenAIRE

    Maurer, Martin H.

    2016-01-01

    Whereas genomics describes the study of genome, mainly represented by its gene expression on the DNA or RNA level, the term proteomics denotes the study of the proteome, which is the protein complement encoded by the genome. In recent years, the number of proteomic experiments increased tremendously. While all fields of proteomics have made major technological advances, the biggest step was seen in bioinformatics. Biological information management relies on sequence and structure databases an...

  14. Hunting for CDF multi-muon ''ghost'' events at collider and fixed-target experiments

    International Nuclear Information System (INIS)

    Bornhauser, Nicki; Drees, Manuel

    2011-01-01

    In 2008 the CDF collaboration discovered a large excess of events containing two or more muons, at least one of which seemed to have been produced outside the beam pipe. We investigate whether similar ''ghost'' events could (and should) have been seen in already completed experiments. The CDF di-muon data can be reproduced by a simple model where a relatively light X particle undergoes 4-body decay. This model predicts a large number of ghost events in Fermilab fixed-target experiments E772, E789 and E866, applying the cuts optimized for analyses of Drell-Yan events. A correct description of events with more than two muons requires a more complicated model, where two X particles are produced from a very broad resonance Y. This model can be tested in fixed-target experiments only if the cut on the angles, or rapidities, of the muons can be relaxed. Either way, the UA1 experiment at the CERN p anti p collider should have observed O(100) ghost events. (orig.)

  15. A comprehensive compilation of SUMO proteomics

    DEFF Research Database (Denmark)

    Hendriks, Ivo A; Vertegaal, Alfred C O

    2016-01-01

    Small ubiquitin-like modifiers (SUMOs) are essential for the regulation of several cellular processes and are potential therapeutic targets owing to their involvement in diseases such as cancer and Alzheimer disease. In the past decade, we have witnessed a rapid expansion of proteomic approaches ...

  16. Quarkonium Physics at a Fixed-Target Experiment Using the LHC Beams

    Energy Technology Data Exchange (ETDEWEB)

    Lansberg, J.P.; /Orsay, IPN; Brodsky, S.J.; /SLAC; Fleuret, F.; /Ecole Polytechnique; Hadjidakis, C.; /Orsay, IPN

    2012-04-09

    We outline the many quarkonium-physics opportunities offered by a multi-purpose fixed-target experiment using the p and Pb LHC beams extracted by a bent crystal. This provides an integrated luminosity of 0.5 fb{sup -1} per year on a typical 1cm-long target. Such an extraction mode does not alter the performance of the collider experiments at the LHC. With such a high luminosity, one can analyse quarkonium production in great details in pp, pd and pA collisions at {radical}s{sub NN} {approx_equal} 115 GeV and at {radical}s{sub NN} {approx_equal} 72 GeV in PbA collisions. In a typical pp (pA) run, the obtained quarkonium yields per unit of rapidity are 2-3 orders of magnitude larger than those expected at RHIC and about respectively 10 (70) times larger than for ALICE. In PbA, they are comparable. By instrumenting the target-rapidity region, the large negative-x{sub F} domain can be accessed for the first time, greatly extending previous measurements by Hera-B and E866. Such analyses should help resolving the quarkonium-production controversies and clear the way for gluon PDF extraction via quarkonium studies. The nuclear target-species versatility provides a unique opportunity to study nuclear matter and the features of the hot and dense matter formed in PbA collisions. A polarised proton target allows the study of transverse-spin asymmetries in J/{Psi} and {Upsilon} production, providing access to the gluon and charm Sivers functions.

  17. When the target may know better : Effects of experience and information asymmetries on value from mergers and acquisitions

    NARCIS (Netherlands)

    Cuypers, I.R.P.; Cuypers, Y.K.; Martin, Xavier

    2017-01-01

    Research Summary: Extending research on the effect of experience on acquisition outcomes, we examine how the differential in previous M&A experience between the target and the acquirer affects the value they respectively obtain when the acquirer takes over the target. Drawing on literature about

  18. An improved method of sample preparation on AnchorChip targets for MALDI-MS and MS/MS and its application in the liver proteome project

    DEFF Research Database (Denmark)

    Zhang, Xumin; Shi, Liang; Shu, Shaokung

    2007-01-01

    An improved method for sample preparation for MALDI-MS and MS/MS using AnchorChip targets is presented. The method, termed the SMW method (sample, matrix wash), results in better sensitivity for peptide mass fingerprinting as well as for sequencing by MS/MS than previously published methods. The ...

  19. Intraoperative Boost Radiotherapy during Targeted Oncoplastic Breast Surgery: Overview and Single Center Experiences

    Directory of Open Access Journals (Sweden)

    Wolfram Malter

    2014-01-01

    Full Text Available Breast-conserving surgery followed by whole-breast irradiation is the standard local therapy for early breast cancer. The international discussion of reduced importance of wider tumor-free resection margins than “tumor not touching ink” leads to the development of five principles in targeted oncoplastic breast surgery. IORT improves local recurrence risk and diminishes toxicity since there is less irradiation of healthy tissue. Intraoperative radiotherapy (IORT can be delivered in two settings: an IORT boost followed by a conventional regimen of external beam radiotherapy or a single IORT dose. The data from TARGIT-A and ELIOT reinforce the conviction that intraoperative radiotherapy during breast-conserving surgery is a reliable alternative to conventional postoperative fractionated irradiation, but only in a carefully selected population at low risk of local recurrence. We describe our experiences with IORT boost (50 kV energy X-rays; 20 Gy in combination with targeted oncoplastic breast surgery in a routine clinical setting. Our experiences demonstrate the applicability and reliability of combining IORT boost with targeted oncoplastic breast surgery in breast-conserving therapy of early breast cancer.

  20. Virtual Labs in proteomics: new E-learning tools.

    Science.gov (United States)

    Ray, Sandipan; Koshy, Nicole Rachel; Reddy, Panga Jaipal; Srivastava, Sanjeeva

    2012-05-17

    Web-based educational resources have gained enormous popularity recently and are increasingly becoming a part of modern educational systems. Virtual Labs are E-learning platforms where learners can gain the experience of practical experimentation without any direct physical involvement on real bench work. They use computerized simulations, models, videos, animations and other instructional technologies to create interactive content. Proteomics being one of the most rapidly growing fields of the biological sciences is now an important part of college and university curriculums. Consequently, many E-learning programs have started incorporating the theoretical and practical aspects of different proteomic techniques as an element of their course work in the form of Video Lectures and Virtual Labs. To this end, recently we have developed a Virtual Proteomics Lab at the Indian Institute of Technology Bombay, which demonstrates different proteomics techniques, including basic and advanced gel and MS-based protein separation and identification techniques, bioinformatics tools and molecular docking methods, and their applications in different biological samples. This Tutorial will discuss the prominent Virtual Labs featuring proteomics content, including the Virtual Proteomics Lab of IIT-Bombay, and E-resources available for proteomics study that are striving to make proteomic techniques and concepts available and accessible to the student and research community. This Tutorial is part of the International Proteomics Tutorial Programme (IPTP 14). Details can be found at: http://www.proteomicstutorials.org/. Copyright © 2012 Elsevier B.V. All rights reserved.

  1. The DESI Experiment Part I: Science,Targeting, and Survey Design

    Energy Technology Data Exchange (ETDEWEB)

    Aghamousa, Amir; et al.

    2016-10-31

    DESI (Dark Energy Spectroscopic Instrument) is a Stage IV ground-based dark energy experiment that will study baryon acoustic oscillations (BAO) and the growth of structure through redshift-space distortions with a wide-area galaxy and quasar redshift survey. To trace the underlying dark matter distribution, spectroscopic targets will be selected in four classes from imaging data. We will measure luminous red galaxies up to $z=1.0$. To probe the Universe out to even higher redshift, DESI will target bright [O II] emission line galaxies up to $z=1.7$. Quasars will be targeted both as direct tracers of the underlying dark matter distribution and, at higher redshifts ($ 2.1 < z < 3.5$), for the Ly-$\\alpha$ forest absorption features in their spectra, which will be used to trace the distribution of neutral hydrogen. When moonlight prevents efficient observations of the faint targets of the baseline survey, DESI will conduct a magnitude-limited Bright Galaxy Survey comprising approximately 10 million galaxies with a median $z\\approx 0.2$. In total, more than 30 million galaxy and quasar redshifts will be obtained to measure the BAO feature and determine the matter power spectrum, including redshift space distortions.

  2. Pose Measurement Method and Experiments for High-Speed Rolling Targets in a Wind Tunnel

    Directory of Open Access Journals (Sweden)

    Zhenyuan Jia

    2014-12-01

    Full Text Available High-precision wind tunnel simulation tests play an important role in aircraft design and manufacture. In this study, a high-speed pose vision measurement method is proposed for high-speed and rolling targets in a supersonic wind tunnel. To obtain images with high signal-to-noise ratio and avoid impacts on the aerodynamic shape of the rolling targets, a high-speed image acquisition method based on ultrathin retro-reflection markers is presented. Since markers are small-sized and some of them may be lost when the target is rolling, a novel markers layout with which markers are distributed evenly on the surface is proposed based on a spatial coding method to achieve highly accurate pose information. Additionally, a pose acquisition is carried out according to the mentioned markers layout after removing mismatching points by Case Deletion Diagnostics. Finally, experiments on measuring the pose parameters of high-speed targets in the laboratory and in a supersonic wind tunnel are conducted to verify the feasibility and effectiveness of the proposed method. Experimental results indicate that the position measurement precision is less than 0.16 mm, the pitching and yaw angle precision less than 0.132° and the roll angle precision 0.712°.

  3. Pose measurement method and experiments for high-speed rolling targets in a wind tunnel.

    Science.gov (United States)

    Jia, Zhenyuan; Ma, Xin; Liu, Wei; Lu, Wenbo; Li, Xiao; Chen, Ling; Wang, Zhengqu; Cui, Xiaochun

    2014-12-12

    High-precision wind tunnel simulation tests play an important role in aircraft design and manufacture. In this study, a high-speed pose vision measurement method is proposed for high-speed and rolling targets in a supersonic wind tunnel. To obtain images with high signal-to-noise ratio and avoid impacts on the aerodynamic shape of the rolling targets, a high-speed image acquisition method based on ultrathin retro-reflection markers is presented. Since markers are small-sized and some of them may be lost when the target is rolling, a novel markers layout with which markers are distributed evenly on the surface is proposed based on a spatial coding method to achieve highly accurate pose information. Additionally, a pose acquisition is carried out according to the mentioned markers layout after removing mismatching points by Case Deletion Diagnostics. Finally, experiments on measuring the pose parameters of high-speed targets in the laboratory and in a supersonic wind tunnel are conducted to verify the feasibility and effectiveness of the proposed method. Experimental results indicate that the position measurement precision is less than 0.16 mm, the pitching and yaw angle precision less than 0.132° and the roll angle precision 0.712°.

  4. Optimization of the target system for the hypernuclear experiment at anti PANDA

    Energy Technology Data Exchange (ETDEWEB)

    Bleser, Sebastian; Sanchez Lorente, Alicia; Steinen, Marcell [Helmholtz-Institut Mainz (Germany); Iazzi, Felice [Politecnico di Torino, Turin (Italy); INFN, Turin (Italy); Pochodzalla, Josef; Rittgen, Kai; Sahin, Cihan [Mainz Univ. (Germany). Inst. fuer Kernphysik; Collaboration: PANDA-Collaboration

    2013-07-01

    Gamma spectroscopy of double Λ hypernuclei will be one of the main topics addressed by the anti PANDA experiment at the planned FAIR-Facility at Darmstadt, Germany. For this project a dedicated hypernuclear detector setup will be installed. In addition to the general purpose of the anti PANDA detector it consists of a primary nuclear target for the production of Ξ{sup -}+ anti Ξ pairs, a secondary active target for the formation of hypernuclei and the identification of associated decay products as well as a germanium detector array to perform γ spectroscopy. In order to stop the Ξ{sup -} particles and track pions from the decay of the produced hypernuclei, the secondary target is composed as a compact structure of silicon microstrip detectors and absorber material. Results of the current hardware development will be presented on the poster including stability tests for the primary target chamber, the readout of silicon microstrip detectors with ultra-thin flexible cables to fan out the readout electronics and design studies of support structures for the whole detector setup. On the simulation side a compromise between the stopping of Ξ{sup -} hyperons and the reconstruction accuracy of weak decay pions is discussed.

  5. Muonium production target for the muon g-2/EDM experiment at J-PARC

    Energy Technology Data Exchange (ETDEWEB)

    Kanda, Sohtaro

    2014-08-15

    There is more than three standard-deviations discrepancy between measurement and theoretical prediction of the muon anomalous magnetic moment. We are going to measure the precision value of muon g−2 and search for physics beyond standard model. In addition, we can search for muon EDM which violates CP symmetry. CP violation in charged lepton sector is currently not found. We are developing the “Ultra Cold Muon Beam” instead of tertiary muon beam with electric focusing. Ultra cold muon is realized by laser ionization of muonium (bound state of a muon and an electron) from the production target. Increase of muonium yield is essential for our experimental goal; 0.1ppm statistical precision. Muonium production experiment at J-PARC MLF MUSE is planned in 2012 autumn. In this paper, we discuss the development of muonium production target and positron detector for the study.

  6. Optimization of accelerator target and detector for portal imaging using Monte Carlo simulation and experiment

    International Nuclear Information System (INIS)

    Flampouri, S.; Evans, P.M.; Partridge, M.; Nahum, A.E.; Verhaegen, A.E.; Spezi, E.

    2002-01-01

    Megavoltage portal images suffer from poor quality compared to those produced with kilovoltage x-rays. Several authors have shown that the image quality can be improved by modifying the linear accelerator to generate more low-energy photons. This work addresses the problem of using Monte Carlo simulation and experiment to optimize the beam and detector combination to maximize image quality for a given patient thickness. A simple model of the whole imaging chain was developed for investigation of the effect of the target parameters on the quality of the image. The optimum targets (6 mm thick aluminium and 1.6 mm copper) were installed in an Elekta SL25 accelerator. The first beam will be referred to as Al6 and the second as Cu1.6. A tissue-equivalent contrast phantom was imaged with the 6 MV standard photon beam and the experimental beams with standard radiotherapy and mammography film/screen systems. The arrangement with a thin Al target/mammography system improved the contrast from 1.4 cm bone in 5 cm water to 19% compared with 2% for the standard arrangement of a thick, high-Z target/radiotherapy verification system. The linac/phantom/detector system was simulated with the BEAM/EGS4 Monte Carlo code. Contrast calculated from the predicted images was in good agreement with the experiment (to within 2.5%). The use of MC techniques to predict images accurately, taking into account the whole imaging system, is a powerful new method for portal imaging system design optimization. (author)

  7. Mass Spectrometry for Translational Proteomics: Progress and Clinical Implications

    Energy Technology Data Exchange (ETDEWEB)

    Baker, Erin Shammel; Liu, Tao; Petyuk, Vladislav A.; Burnum-Johnson, Kristin E.; Ibrahim, Yehia M.; Anderson, Gordon A.; Smith, Richard D.

    2012-08-31

    Mass spectrometry (MS)-based proteomics measurements have become increasingly utilized in a wide range of biological and biomedical applications, and have significantly enhanced the understanding of the complex and dynamic nature of the proteome and its connections to biology and diseases. While some MS techniques such as those for targeted analysis are increasingly applied with great success, others such as global quantitative analysis (for e.g. biomarker discovery) are more challenging and continue to be developed and refined to provide the desired throughput, sensitivity and/ or specificity. New MS capabilities and proteomics-based pipelines/strategies also keep enhancing for the advancement of clinical proteomics applications such as protein biomarker discovery and validation. Herein, we provide a brief review to summarize the current state of MS-based proteomics with respect to its advantages and present limitations, while highlighting its potential in future clinical applications.

  8. Proteome alteration induced by hTERT transfection of human fibroblast cells.

    Science.gov (United States)

    Mazzucchelli, Gabriel D; Gabelica, Valérie; Smargiasso, Nicolas; Fléron, Maximilien; Ashimwe, Wilson; Rosu, Frédéric; De Pauw-Gillet, Marie-Claire; Riou, Jean-François; De Pauw, Edwin

    2008-04-17

    Telomerase confers cellular immortality by elongating telomeres, thereby circumventing the Hayflick limit. Extended-life-span cells have been generated by transfection with the human telomerase reverse transcriptase (hTERT) gene. hTERT transfected cell lines may be of outstanding interest to monitor the effect of drugs targeting the telomerase activity. The incidence of hTERT gene transfection at the proteome level is a prerequisite to that purpose. The effect of the transfection has been studied on the proteome of human fibroblast (WI38). Cytosolic and nuclear fractions of WI38 cells, empty vector transfected WI38 (WI38-HPV) and hTERT WI38 cells were submitted to a 2D-DIGE (Two-Dimensional Differential In-Gel Electrophoresis) analysis. Only spots that had a similar abundance in WI38 and WI38-HPV, but were differentially expressed in WI38 hTERT were selected for MS identification. This method directly points to the proteins linked with the hTERT expression. Number of false positive differentially expressed proteins has been excluded by using control WI38-HPV cells. The proteome alteration induced by hTERT WI38 transfection should be taken into account in subsequent use of the cell line for anti-telomerase drugs evaluation. 2D-DIGE experiment shows that 57 spots out of 2246 are significantly differentially expressed in the cytosolic fraction due to hTERT transfection, and 38 were confidently identified. In the nuclear fraction, 44 spots out of 2172 were selected in the differential proteome analysis, and 14 were identified. The results show that, in addition to elongating telomeres, hTERT gene transfection has other physiological roles, among which an enhanced ER capacity and a potent cell protection against apoptosis. We show that the methodology reduces the complexity of the proteome analysis and highlights proteins implicated in other processes than telomere elongation. hTERT induced proteome changes suggest that telomerase expression enhances natural cell repair

  9. Proteome alteration induced by hTERT transfection of human fibroblast cells

    Directory of Open Access Journals (Sweden)

    Riou Jean-François

    2008-04-01

    Full Text Available Abstract Background Telomerase confers cellular immortality by elongating telomeres, thereby circumventing the Hayflick limit. Extended-life-span cells have been generated by transfection with the human telomerase reverse transcriptase (hTERT gene. hTERT transfected cell lines may be of outstanding interest to monitor the effect of drugs targeting the telomerase activity. The incidence of hTERT gene transfection at the proteome level is a prerequisite to that purpose. The effect of the transfection has been studied on the proteome of human fibroblast (WI38. Cytosolic and nuclear fractions of WI38 cells, empty vector transfected WI38 (WI38-HPV and hTERT WI38 cells were submitted to a 2D-DIGE (Two-Dimensional Differential In-Gel Electrophoresis analysis. Only spots that had a similar abundance in WI38 and WI38-HPV, but were differentially expressed in WI38 hTERT were selected for MS identification. This method directly points to the proteins linked with the hTERT expression. Number of false positive differentially expressed proteins has been excluded by using control WI38-HPV cells. The proteome alteration induced by hTERT WI38 transfection should be taken into account in subsequent use of the cell line for anti-telomerase drugs evaluation. Results 2D-DIGE experiment shows that 57 spots out of 2246 are significantly differentially expressed in the cytosolic fraction due to hTERT transfection, and 38 were confidently identified. In the nuclear fraction, 44 spots out of 2172 were selected in the differential proteome analysis, and 14 were identified. The results show that, in addition to elongating telomeres, hTERT gene transfection has other physiological roles, among which an enhanced ER capacity and a potent cell protection against apoptosis. Conclusion We show that the methodology reduces the complexity of the proteome analysis and highlights proteins implicated in other processes than telomere elongation. hTERT induced proteome changes suggest

  10. Proteomic Technologies for the Study of Osteosarcoma

    Directory of Open Access Journals (Sweden)

    Stephanie D. Byrum

    2012-01-01

    Full Text Available Osteosarcoma is the most common primary bone cancer of children and is established during stages of rapid bone growth. The disease is a consequence of immature osteoblast differentiation, which gives way to a rapidly synthesized incompletely mineralized and disorganized bone matrix. The mechanism of osteosarcoma tumorogenesis is poorly understood, and few proteomic studies have been used to interrogate the disease thus far. Accordingly, these studies have identified proteins that have been known to be associated with other malignancies, rather than being osteosarcoma specific. In this paper, we focus on the growing list of available state-of-the-art proteomic technologies and their specific application to the discovery of novel osteosarcoma diagnostic and therapeutic targets. The current signaling markers/pathways associated with primary and metastatic osteosarcoma that have been identified by early-stage proteomic technologies thus far are also described.

  11. Advances in Proteomics of Mycobacterium leprae.

    Science.gov (United States)

    Parkash, O; Singh, B P

    2012-04-01

    Although Mycobacterium leprae was the first bacterial pathogen identified causing human disease, it remains one of the few that is non-cultivable. Understanding the biology of M. leprae is one of the primary challenges in current leprosy research. Genomics has been extremely valuable, nonetheless, functional proteins are ultimately responsible for controlling most aspects of cellular functions, which in turn could facilitate parasitizing the host. Furthermore, bacterial proteins provide targets for most of the vaccines and immunodiagnostic tools. Better understanding of the proteomics of M. leprae could also help in developing new drugs against M. leprae. During the past nearly 15 years, there have been several developments towards the identification of M. leprae proteins employing contemporary proteomics tools. In this review, we discuss the knowledge gained on the biology and pathogenesis of M. leprae from current proteomic studies. © 2012 The Authors. Scandinavian Journal of Immunology © 2012 Blackwell Publishing Ltd.

  12. The Use of Proteomics in Assisted Reproduction.

    Science.gov (United States)

    Kosteria, Ioanna; Anagnostopoulos, Athanasios K; Kanaka-Gantenbein, Christina; Chrousos, George P; Tsangaris, George T

    2017-01-01

    Despite the explosive increase in the use of Assisted Reproductive Technologies (ART) over the last 30 years, their success rates remain suboptimal. Proteomics is a rapidly-evolving technology-driven science that has already been widely applied in the exploration of human reproduction and fertility, providing useful insights into its physiology and leading to the identification of numerous proteins that may be potential biomarkers and/or treatment targets of a successful ART pregnancy. Here we present a brief overview of the techniques used in proteomic analyses and attempt a comprehensive presentation of recent data from mass spectrometry-based proteomic studies in humans, regarding all components of ARTs, including the male and female gamete, the derived zygote and embryo, the endometrium and, finally, the ART offspring both pre- and postnatally. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  13. Knowledge Translation: Moving Proteomics Science to Innovation in Society.

    Science.gov (United States)

    Holmes, Christina; McDonald, Fiona; Jones, Mavis; Graham, Janice

    2016-06-01

    Proteomics is one of the pivotal next-generation biotechnologies in the current "postgenomics" era. Little is known about the ways in which innovative proteomics science is navigating the complex socio-political space between laboratory and society. It cannot be assumed that the trajectory between proteomics laboratory and society is linear and unidirectional. Concerned about public accountability and hopes for knowledge-based innovations, funding agencies and citizens increasingly expect that emerging science and technologies, such as proteomics, are effectively translated and disseminated as innovation in society. Here, we describe translation strategies promoted in the knowledge translation (KT) and science communication literatures and examine the use of these strategies within the field of proteomics. Drawing on data generated from qualitative interviews with proteomics scientists and ethnographic observation of international proteomics conferences over a 5-year period, we found that proteomics science incorporates a variety of KT strategies to reach knowledge users outside the field. To attain the full benefit of KT, however, proteomics scientists must challenge their own normative assumptions and approaches to innovation dissemination-beyond the current paradigm relying primarily on publication for one's scientific peers within one's field-and embrace the value of broader (interdisciplinary) KT strategies in promoting the uptake of their research. Notably, the Human Proteome Organization (HUPO) is paying increasing attention to a broader range of KT strategies, including targeted dissemination, integrated KT, and public outreach. We suggest that increasing the variety of KT strategies employed by proteomics scientists is timely and would serve well the omics system sciences community.

  14. HTCAP-1: a program for calcuating operating temperatures in HFIR target irradiation experiments

    International Nuclear Information System (INIS)

    Kania, M.J.; Howard, A.M.

    1980-06-01

    The thermal modeling code, HTCAP-1, calculates in-reactor operating temperatures of fueled specimens contained in the High Flux Isotope Reactor (HFIR) target irradiation experiments (HT-series). Temperature calculations are made for loose particle and bonded fuel rod specimens. Maximum particle surface temperatures are calculated for the loose particles and centerline and surface temperatures for the fuel rods. Three computational models are employed to determine fission heat generation rates, capsule heat transfer analysis, and specimen temperatures. This report is also intended to be a users' manual, and the application of HTCAP-1 to the HT-34 irradiation capsule is presented

  15. Do non-monetary prices target the poor? Evidence from a field experiment in India

    OpenAIRE

    Hoffmann, Bridget

    2016-01-01

    This paper uses willingness to pay (WTP) data from a field experiment in Hyderabad, India in 2013 to determine whether non-monetary prices better target health products to the poor than monetary prices. Monetary WTP is increasing in income and non-monetary WTP is weakly decreasing in income. Household fixed effects in a pooled sample of monetary WTP and non-monetary WTP are used to compare the correlation of income and WTP across price types. It is found that non-monetary WTP falls relative t...

  16. A monocrystal of 59Co as a nuclear orientation thermometer in neutron experiments with oriented targets

    International Nuclear Information System (INIS)

    Fasoli, U.; Galeazzi, G.; Pavan, P.; Toniolo, D.; Zago, G.; Zannoni, R.

    1980-01-01

    An apparatus for measuring temperatures in the millikelvin region is described based on the 'deformation effect' on fast neutron transmission through an aligned 59 Co monocrystal, employing a 252 Cf pill as the neutron source. A statistical accuracy of a few percent in a few minutes is obtainable with a heat input of some tens of pW. The apparatus is suitable in neutron experiments with oriented targets when the gamma-ray background hinders the use of gamma-ray anisotropy thermometers. In these and similar cases, in which the temperature must be held constant for long periods, the large heat capacity of the cobalt sample is not a drawback. (orig.)

  17. HIV/STI interventions targeting women who experience forced sex: A systematic review of global literature.

    Science.gov (United States)

    Deming, Michelle E; Bhochhibhoya, Amir; Ingram, LaDrea; Stafford, Crystal; Li, Xiaoming

    2018-04-12

    Women are disproportionately affected by HIV in many regions of the world and they represent the fastest growing demographic in the HIV epidemic. In addition, sexual violence against women is a global public health issue which increases women's vulnerability of HIV/STI acquisition. However, the relationship between sexual violence and HIV/STI risk are complex and contribute to the growing epidemic of women infected with HIV/STIs. Our purpose for this review is to examine existing HIV/STI interventions that target women who experience forced sex. Interventions designed to address women's unique needs in HIV/STI prevention are critical in reducing women's vulnerability to HIV/STIs.

  18. Comparative Proteomic Analysis Provides insight into the Key Proteins as Possible Targets Involved in Aspirin Inhibiting Biofilm Formation of Staphylococcus xylosus

    Directory of Open Access Journals (Sweden)

    Chang-Geng Xu

    2017-08-01

    Full Text Available Staphylococcus xylosus is an opportunistic pathogen that causes infection in humans and cow mastitis. And S. xylosus possesses a strong ability to form biofilms in vitro. As biofilm formation facilitates resistance to antimicrobial agents, the discovery of new medicinal properties for classic drugs is highly desired. Aspirin, which is the most common active component of non-steroidal anti-inflammatory compounds, affects the biofilm-forming capacity of various bacterial species. We have found that aspirin effectively inhibits biofilm formation of S. xylosus by Crystal violet (CV staining and scanning electron microscopy analyses. The present study sought to elucidate possible targets of aspirin in suppressing S. xylosus biofilm formation. Based on an isobaric tag for relative and absolute quantitation (iTRAQ fold-change of >1.2 or <0.8 (P-value < 0.05, 178 differentially expressed proteins, 111 down-regulated and 67 up-regulated, were identified after application of aspirin to cells at a 1/2 minimal inhibitory concentration. Gene ontology analysis indicated enrichment in metabolic processes for the majority of the differentially expressed proteins. We then used the Kyoto Encyclopedia of Genes and Genomes (KEGG pathway database to analyze a large number of differentially expressed proteins and identified genes involved in biosynthesis of amino acids pathway, carbon metabolism (pentose phosphate and glycolytic pathways, tricarboxylic acid cycle and nitrogen metabolism (histidine metabolism. These novel proteins represent candidate targets in aspirin-mediated inhibition of S. xylosus biofilm formation at sub-MIC levels. The findings lay the foundation for further studies to identify potential aspirin targets.

  19. Observation of the charge neutrality of the ions from target short-pulse laser interaction experiments

    International Nuclear Information System (INIS)

    Yasuike, Kazuhito

    2003-01-01

    Intended to simulate the early stage of the plasma (preformed plasma) formation in the higher (10 20 W cm -2 ) intensity experiments (in which the plasma density profile rules laser absorption thus conversion efficiency from laser into hot electrons, ions and x-rays) experiments using solid target were done under a peak intensity (main laser pulse) of up to ∼10 15 W cm -2 and pre-pulse and pedestal intensity of ∼10 3 times lower than main pulse. With pedestal, significant enhancement of laser absorption was observed with pedestal condition. Charge neutralization of the ions from the plasma was measured by biased charge collectors. Earlier part of the ion were almost un-neutralized in with or without pedestal condition, and the later part of the ions (≤ few keV) were partially neutralized (≥40%). These not-perfect charge neutralization results is different from the longer nano-seconds pulse experimental results. (author)

  20. Use of a track and vertex processor in a fixed-target charm experiment

    International Nuclear Information System (INIS)

    Schub, M.H.; Carey, T.A.; Hsiung, Y.B.; Kaplan, D.M.; Lee, C.; Miller, G.; Sa, J.; Teng, P.K.

    1996-01-01

    We have constructed and operated a high-speed parallel-pipelined track and vertex processor and used it to trigger data acquisition in a high-rate charm and beauty experiment at Fermilab. The processor uses information from hodoscopes and wire chambers to reconstruct tracks in the bend view of a magnetic spectrometer, and uses these tracks to find the corresponding tracks in a set of silicon-strip detectors. The processor then forms vertices and triggers the experiment if at least one vertex is downstream of the target. Under typical charm running conditions, with an interaction rate of ∼5 MHz, the processor rejects 80-90% of lower-level triggers while maintaining efficiency of ∼70% for two-prong D-meson decays. (orig.)

  1. Proteomics in medical microbiology.

    Science.gov (United States)

    Cash, P

    2000-04-01

    The techniques of proteomics (high resolution two-dimensional electrophoresis and protein characterisation) are widely used for microbiological research to analyse global protein synthesis as an indicator of gene expression. The rapid progress in microbial proteomics has been achieved through the wide availability of whole genome sequences for a number of bacterial groups. Beyond providing a basic understanding of microbial gene expression, proteomics has also played a role in medical areas of microbiology. Progress has been made in the use of the techniques for investigating the epidemiology and taxonomy of human microbial pathogens, the identification of novel pathogenic mechanisms and the analysis of drug resistance. In each of these areas, proteomics has provided new insights that complement genomic-based investigations. This review describes the current progress in these research fields and highlights some of the technical challenges existing for the application of proteomics in medical microbiology. The latter concern the analysis of genetically heterogeneous bacterial populations and the integration of the proteomic and genomic data for these bacteria. The characterisation of the proteomes of bacterial pathogens growing in their natural hosts remains a future challenge.

  2. Quantitative Proteome Analysis of Mouse Liver Lysosomes Provides Evidence for Mannose 6-phosphate-independent Targeting Mechanisms of Acid Hydrolases in Mucolipidosis II.

    Science.gov (United States)

    Markmann, Sandra; Krambeck, Svenja; Hughes, Christopher J; Mirzaian, Mina; Aerts, Johannes M F G; Saftig, Paul; Schweizer, Michaela; Vissers, Johannes P C; Braulke, Thomas; Damme, Markus

    2017-03-01

    The efficient receptor-mediated targeting of soluble lysosomal proteins to lysosomes requires the modification with mannose 6-phosphate (M6P) residues. Although the absence of M6P results in misrouting and hypersecretion of lysosomal enzymes in many cells, normal levels of lysosomal enzymes have been reported in liver of patients lacking the M6P-generating phosphotransferase (PT). The identity of lysosomal proteins depending on M6P has not yet been comprehensively analyzed. In this study we purified lysosomes from liver of PT-defective mice and 67 known soluble lysosomal proteins were identified that illustrated quantitative changes using an ion mobility-assisted data-independent label-free LC-MS approach. After validation of various differentially expressed lysosomal components by Western blotting and enzyme activity assays, the data revealed a small number of lysosomal proteins depending on M6P, including neuraminidase 1, cathepsin F, Npc2, and cathepsin L, whereas the majority reach lysosomes by alternative pathways. These data were compared with findings on cultured hepatocytes and liver sinusoid endothelial cells isolated from the liver of wild-type and PT-defective mice. Our findings show that the relative expression, targeting efficiency and lysosomal localization of lysosomal proteins tested in cultured hepatic cells resemble their proportion in isolated liver lysosomes. Hypersecretion of newly synthesized nonphosphorylated lysosomal proteins suggest that secretion-recapture mechanisms contribute to maintain major lysosomal functions in liver. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  3. Deeply Virtual Compton Scattering off a deuterium target at the HERMES experiment

    International Nuclear Information System (INIS)

    Movsisyan, Aram

    2011-05-01

    Deeply virtual Compton scattering is studied in this report, using all data collected at the HERMES experiment from 1996 to 2005. Azimuthal asymmetries with respect to beam-helicity, beam-charge and target polarization alone and also to their different combinations for hard exclusive electroproduction of real photons in deep-inelastic scattering from a both unpolarized and longitudinally polarized deuterium targets are measured. The asymmetries are attributed to the interference between the deeply virtual Compton scattering and Bethe-Heitler processes. The asymmetries are observed in the exclusive region -(1.5) 2 GeV 2 2 X 2 GeV 2 of the squared missing mass. The dependences of these asymmetries on -t, x N , or Q 2 are investigated. The results include the coherent process ed→edγ and the incoherent process ed→epnγ where in addition a nucleon may be excited to a resonance. For an unpolarized deuterium target, the leading Fourier amplitude of the beam-helicity asymmetry that is sensitive to the interference term is found to be substantial, but no significant t dependence is observed. The leading amplitude of the beam-charge asymmetry is substantial at large -t, but becomes small at small values of -t. The amplitudes of the beam-helicity asymmetry that are sensitive to the squared DVCS term are found to be consistent with zero. The deuteron Compton form factor H 1 appears to have a similar behavior as H of the proton. (orig.)

  4. Injector design for liner-on-target gas-puff experiments

    Science.gov (United States)

    Valenzuela, J. C.; Krasheninnikov, I.; Conti, F.; Wessel, F.; Fadeev, V.; Narkis, J.; Ross, M. P.; Rahman, H. U.; Ruskov, E.; Beg, F. N.

    2017-11-01

    We present the design of a gas-puff injector for liner-on-target experiments. The injector is composed of an annular high atomic number (e.g., Ar and Kr) gas and an on-axis plasma gun that delivers an ionized deuterium target. The annular supersonic nozzle injector has been studied using Computational Fluid Dynamics (CFD) simulations to produce a highly collimated (M > 5), ˜1 cm radius gas profile that satisfies the theoretical requirement for best performance on ˜1-MA current generators. The CFD simulations allowed us to study output density profiles as a function of the nozzle shape, gas pressure, and gas composition. We have performed line-integrated density measurements using a continuous wave (CW) He-Ne laser to characterize the liner gas density. The measurements agree well with the CFD values. We have used a simple snowplow model to study the plasma sheath acceleration in a coaxial plasma gun to help us properly design the target injector.

  5. Physics perspectives with AFTER@LHC (A Fixed Target ExpeRiment at LHC

    Directory of Open Access Journals (Sweden)

    Massacrier L.

    2018-01-01

    Full Text Available AFTER@LHC is an ambitious fixed-target project in order to address open questions in the domain of proton and neutron spins, Quark Gluon Plasma and high-x physics, at the highest energy ever reached in the fixed-target mode. Indeed, thanks to the highly energetic 7 TeV proton and 2.76 A.TeV lead LHC beams, center-of-mass energies as large as sNN = 115 GeV in pp/pA and sNN = 72 GeV in AA can be reached, corresponding to an uncharted energy domain between SPS and RHIC. We report two main ways of performing fixed-target collisions at the LHC, both allowing for the usage of one of the existing LHC experiments. In these proceedings, after discussing the projected luminosities considered for one year of data taking at the LHC, we will present a selection of projections for light and heavy-flavour production.

  6. Development And Characterization Of A Liner-On-Target Injector For Staged Z-Pinch Experiments

    Science.gov (United States)

    Valenzuela, J. C.; Conti, F.; Krasheninnikov, I.; Narkis, J.; Beg, F.; Wessel, F. J.; Rahman, H. U.

    2016-10-01

    We present the design and optimization of a liner-on-target injector for Staged Z-pinch experiments. The injector is composed of an annular high atomic number (e.g. Ar, Kr) gas-puff and an on-axis plasma gun that delivers the ionized deuterium target. The liner nozzle injector has been carefully studied using Computational Fluid Dynamics (CFD) simulations to produce a highly collimated 1 cm radius gas profile that satisfies the theoretical requirement for best performance on the 1 MA Zebra current driver. The CFD simulations produce density profiles as a function of the nozzle shape and gas. These profiles are initialized in the MHD MACH2 code to find the optimal liner density for a stable, uniform implosion. We use a simple Snowplow model to study the plasma sheath acceleration in a coaxial plasma gun to help us properly design the target injector. We have performed line-integrated density measurements using a CW He-Ne laser to characterize the liner gas and the plasma gun density as a function of time. The measurements are compared with models and calculations and benchmarked accordingly. Advanced Research Projects Agency - Energy, DE-AR0000569.

  7. Optimized beryllium target design for indirectly driven inertial confinement fusion experiments on the National Ignition Facility

    Energy Technology Data Exchange (ETDEWEB)

    Simakov, Andrei N., E-mail: simakov@lanl.gov; Wilson, Douglas C.; Yi, Sunghwan A.; Kline, John L.; Batha, Steven H. [Los Alamos National Laboratory, P.O. Box 1663, Los Alamos, New Mexico 87545 (United States); Clark, Daniel S.; Milovich, Jose L.; Salmonson, Jay D. [Lawrence Livermore National Laboratory, P.O. Box 808, Livermore, California 94551 (United States)

    2014-02-15

    For indirect drive inertial confinement fusion, Beryllium (Be) ablators offer a number of important advantages as compared with other ablator materials, e.g., plastic and high density carbon. In particular, the low opacity and relatively high density of Be lead to higher rocket efficiencies giving a higher fuel implosion velocity for a given X-ray drive; and to higher ablation velocities providing more ablative stabilization and reducing the effect of hydrodynamic instabilities on the implosion performance. Be ablator advantages provide a larger target design optimization space and can significantly improve the National Ignition Facility (NIF) [J. D. Lindl et al., Phys. Plasmas 11, 339 (2004)] ignition margin. Herein, we summarize the Be advantages, briefly review NIF Be target history, and present a modern, optimized, low adiabat, Revision 6 NIF Be target design. This design takes advantage of knowledge gained from recent NIF experiments, including more realistic levels of laser-plasma energy backscatter, degraded hohlraum-capsule coupling, and the presence of cross-beam energy transfer.

  8. NCI Blog Post: CPTAC, the Complementary Sibling of TCGA (An Interview with Dr. Henry Rodriguez about NCI’s Proteomics Program) | Office of Cancer Clinical Proteomics Research

    Science.gov (United States)

    What is proteomics? Proteomics is a highly automated and rapid method for measuring all the proteins in a biological sample. Proteins are the molecules that actually do most of the work inside a cell. When researchers develop cancer drugs, those drugs typically target proteins, so scientists and clinicians really have to understand what the proteins are doing. Proteomics researchers are now able to measure up to 10,000 proteins per tumor sample.

  9. On the feasibility to perform integral transmission experiments in the GELINA target hall at IRMM

    Science.gov (United States)

    Leconte, Pierre; Jean, Cyrille De Saint; Geslot, Benoit; Plompen, Arjan; Belloni, Francesca; Nyman, Markus

    2017-09-01

    Shielding experiments are relevant to validate elastic and inelastic scattering cross sections in the fast energy range. In this paper, we are focusing on the possibility to use the pulsed white neutron time-of-flight facility GELINA to perform this kind of measurement. Several issues need to be addressed: neutron source intensity, room return effect, distance of the materials to be irradiated from the source, and the sensitivity of various reaction rate distributions through the material to different input cross sections. MCNP6 and TRIPOLI4 calculations of the outgoing neutron spectrum are compared, based on electron/positron/gamma/neutron simulations. A first guess of an integral transmission experiment through a 238U slab is considered. It shows that a 10 cm thickness of uranium is sufficient to reach a high sensitivity to the 238U inelastic scattering cross section in the [2-5 MeV] energy range, with small contributions from elastic and fission cross sections. This experiment would contribute to reduce the uncertainty on this nuclear data, which has a significant impact on the power distribution in large commercial reactors. Other materials that would be relevant for the ASTRID 4th generation prototype reactor are also tested, showing that a sufficient sensitivity to nuclear data would be obtained by using a 50 to 100cm thick slab of side 60x60cm. This study concludes on the feasibility and interest of such experiments in the target hall of the GELINA facility.

  10. Anomalons, recent copper-target experiments and the first law of thermodynamics

    International Nuclear Information System (INIS)

    Brandt, R.; Khan, H.A.; Krivopustov, M.I.

    1991-01-01

    A reanalysis of the old Alexander experiment, reporting on the anomalous behavior of pie in K-decays indicates that this anomalous behavior may be connected to a state of lower entropy or in other words to 'anomalous information', considering the well-known relation: negative entropy information. Now, recent copper-target experiments from the Synchrophasotron entail, that the wide-angle emission of hadrons in the reaction (44 GeV/sup 12/c + Cu) cannot be understood with concepts of physics, as known to the authors. However, this could be understood with 'anomalous information'. Further effects of this 'anomalous information' may be obtained in future studies with very massive heavy element targets irradiated with relativistic ions. The total production of neutrons in such a system could both be measured experimentally and calculated theoretically. As the calculations are based on the 1st Law of Thermodynamic, a significant excess of neutron fluxes beyond calculations may indicate the effete of anomalous information, even on the expense of the 1st law of Thermodynamics. (Orig./A.B.)

  11. Quantitative Proteomics Reveals Temporal Proteomic Changes in Signaling Pathways during BV2 Mouse Microglial Cell Activation.

    Science.gov (United States)

    Woo, Jongmin; Han, Dohyun; Wang, Joseph Injae; Park, Joonho; Kim, Hyunsoo; Kim, Youngsoo

    2017-09-01

    The development of systematic proteomic quantification techniques in systems biology research has enabled one to perform an in-depth analysis of cellular systems. We have developed a systematic proteomic approach that encompasses the spectrum from global to targeted analysis on a single platform. We have applied this technique to an activated microglia cell system to examine changes in the intracellular and extracellular proteomes. Microglia become activated when their homeostatic microenvironment is disrupted. There are varying degrees of microglial activation, and we chose to focus on the proinflammatory reactive state that is induced by exposure to such stimuli as lipopolysaccharide (LPS) and interferon-gamma (IFN-γ). Using an improved shotgun proteomics approach, we identified 5497 proteins in the whole-cell proteome and 4938 proteins in the secretome that were associated with the activation of BV2 mouse microglia by LPS or IFN-γ. Of the differentially expressed proteins in stimulated microglia, we classified pathways that were related to immune-inflammatory responses and metabolism. Our label-free parallel reaction monitoring (PRM) approach made it possible to comprehensively measure the hyper-multiplex quantitative value of each protein by high-resolution mass spectrometry. Over 450 peptides that corresponded to pathway proteins and direct or indirect interactors via the STRING database were quantified by label-free PRM in a single run. Moreover, we performed a longitudinal quantification of secreted proteins during microglial activation, in which neurotoxic molecules that mediate neuronal cell loss in the brain are released. These data suggest that latent pathways that are associated with neurodegenerative diseases can be discovered by constructing and analyzing a pathway network model of proteins. Furthermore, this systematic quantification platform has tremendous potential for applications in large-scale targeted analyses. The proteomics data for

  12. Scattering from extended targets in range-dependent fluctuating ocean-waveguides with clutter from theory and experiments.

    Science.gov (United States)

    Jagannathan, Srinivasan; Küsel, Elizabeth T; Ratilal, Purnima; Makris, Nicholas C

    2012-08-01

    Bistatic, long-range measurements of acoustic scattered returns from vertically extended, air-filled tubular targets were made during three distinct field experiments in fluctuating continental shelf waveguides. It is shown that Sonar Equation estimates of mean target-scattered intensity lead to large errors, differing by an order of magnitude from both the measurements and waveguide scattering theory. The use of the Ingenito scattering model is also shown to lead to significant errors in estimating mean target-scattered intensity in the field experiments because they were conducted in range-dependent ocean environments with large variations in sound speed structure over the depth of the targets, scenarios that violate basic assumptions of the Ingenito model. Green's theorem based full-field modeling that describes scattering from vertically extended tubular targets in range-dependent ocean waveguides by taking into account nonuniform sound speed structure over the target's depth extent is shown to accurately describe the statistics of the targets' scattered field in all three field experiments. Returns from the man-made targets are also shown to have a very different spectral dependence from the natural target-like clutter of the dominant fish schools observed, suggesting that judicious multi-frequency sensing may often provide a useful means of distinguishing fish from man-made targets.

  13. Proteome-wide dataset supporting the study of ancient metazoan macromolecular complexes

    Directory of Open Access Journals (Sweden)

    Sadhna Phanse

    2016-03-01

    Full Text Available Our analysis examines the conservation of multiprotein complexes among metazoa through use of high resolution biochemical fractionation and precision mass spectrometry applied to soluble cell extracts from 5 representative model organisms Caenorhabditis elegans, Drosophila melanogaster, Mus musculus, Strongylocentrotus purpuratus, and Homo sapiens. The interaction network obtained from the data was validated globally in 4 distant species (Xenopus laevis, Nematostella vectensis, Dictyostelium discoideum, Saccharomyces cerevisiae and locally by targeted affinity-purification experiments. Here we provide details of our massive set of supporting biochemical fractionation data available via ProteomeXchange (http://www.ebi.ac.uk/pride/archive/projects/PXD002319-http://www.ebi.ac.uk/pride/archive/projects/PXD002328, PPIs via BioGRID (185267; and interaction network projections via (http://metazoa.med.utoronto.ca made fully accessible to allow further exploration. The datasets here are related to the research article on metazoan macromolecular complexes in Nature [1]. Keywords: Proteomics, Metazoa, Protein complexes, Biochemical, Fractionation

  14. Proteomics of Trypanosoma evansi infection in rodents.

    Science.gov (United States)

    Roy, Nainita; Nageshan, Rishi Kumar; Pallavi, Rani; Chakravarthy, Harshini; Chandran, Syama; Kumar, Rajender; Gupta, Ashok Kumar; Singh, Raj Kumar; Yadav, Suresh Chandra; Tatu, Utpal

    2010-03-22

    Trypanosoma evansi infections, commonly called 'surra', cause significant economic losses to livestock industry. While this infection is mainly restricted to large animals such as camels, donkeys and equines, recent reports indicate their ability to infect humans. There are no World Animal Health Organization (WAHO) prescribed diagnostic tests or vaccines available against this disease and the available drugs show significant toxicity. There is an urgent need to develop improved methods of diagnosis and control measures for this disease. Unlike its related human parasites T. brucei and T. cruzi whose genomes have been fully sequenced T. evansi genome sequence remains unavailable and very little efforts are being made to develop improved methods of prevention, diagnosis and treatment. With a view to identify potential diagnostic markers and drug targets we have studied the clinical proteome of T. evansi infection using mass spectrometry (MS). Using shot-gun proteomic approach involving nano-lc Quadrupole Time Of Flight (QTOF) mass spectrometry we have identified over 160 proteins expressed by T. evansi in mice infected with camel isolate. Homology driven searches for protein identification from MS/MS data led to most of the matches arising from related Trypanosoma species. Proteins identified belonged to various functional categories including metabolic enzymes; DNA metabolism; transcription; translation as well as cell-cell communication and signal transduction. TCA cycle enzymes were strikingly missing, possibly suggesting their low abundances. The clinical proteome revealed the presence of known and potential drug targets such as oligopeptidases, kinases, cysteine proteases and more. Previous proteomic studies on Trypanosomal infections, including human parasites T. brucei and T. cruzi, have been carried out from lab grown cultures. For T. evansi infection this is indeed the first ever proteomic study reported thus far. In addition to providing a glimpse into the

  15. Proteomics of Trypanosoma evansi infection in rodents.

    Directory of Open Access Journals (Sweden)

    Nainita Roy

    2010-03-01

    Full Text Available Trypanosoma evansi infections, commonly called 'surra', cause significant economic losses to livestock industry. While this infection is mainly restricted to large animals such as camels, donkeys and equines, recent reports indicate their ability to infect humans. There are no World Animal Health Organization (WAHO prescribed diagnostic tests or vaccines available against this disease and the available drugs show significant toxicity. There is an urgent need to develop improved methods of diagnosis and control measures for this disease. Unlike its related human parasites T. brucei and T. cruzi whose genomes have been fully sequenced T. evansi genome sequence remains unavailable and very little efforts are being made to develop improved methods of prevention, diagnosis and treatment. With a view to identify potential diagnostic markers and drug targets we have studied the clinical proteome of T. evansi infection using mass spectrometry (MS.Using shot-gun proteomic approach involving nano-lc Quadrupole Time Of Flight (QTOF mass spectrometry we have identified over 160 proteins expressed by T. evansi in mice infected with camel isolate. Homology driven searches for protein identification from MS/MS data led to most of the matches arising from related Trypanosoma species. Proteins identified belonged to various functional categories including metabolic enzymes; DNA metabolism; transcription; translation as well as cell-cell communication and signal transduction. TCA cycle enzymes were strikingly missing, possibly suggesting their low abundances. The clinical proteome revealed the presence of known and potential drug targets such as oligopeptidases, kinases, cysteine proteases and more.Previous proteomic studies on Trypanosomal infections, including human parasites T. brucei and T. cruzi, have been carried out from lab grown cultures. For T. evansi infection this is indeed the first ever proteomic study reported thus far. In addition to providing a

  16. Bacterial membrane proteomics.

    Science.gov (United States)

    Poetsch, Ansgar; Wolters, Dirk

    2008-10-01

    About one quarter to one third of all bacterial genes encode proteins of the inner or outer bacterial membrane. These proteins perform essential physiological functions, such as the import or export of metabolites, the homeostasis of metal ions, the extrusion of toxic substances or antibiotics, and the generation or conversion of energy. The last years have witnessed completion of a plethora of whole-genome sequences of bacteria important for biotechnology or medicine, which is the foundation for proteome and other functional genome analyses. In this review, we discuss the challenges in membrane proteome analysis, starting from sample preparation and leading to MS-data analysis and quantification. The current state of available proteomics technologies as well as their advantages and disadvantages will be described with a focus on shotgun proteomics. Then, we will briefly introduce the most abundant proteins and protein families present in bacterial membranes before bacterial membrane proteomics studies of the last years will be presented. It will be shown how these works enlarged our knowledge about the physiological adaptations that take place in bacteria during fine chemical production, bioremediation, protein overexpression, and during infections. Furthermore, several examples from literature demonstrate the suitability of membrane proteomics for the identification of antigens and different pathogenic strains, as well as the elucidation of membrane protein structure and function.

  17. A proteomic perspective of inbuilt viral protein regulation: pUL46 tegument protein is targeted for degradation by ICP0 during herpes simplex virus type 1 infection.

    Science.gov (United States)

    Lin, Aaron E; Greco, Todd M; Döhner, Katinka; Sodeik, Beate; Cristea, Ileana M

    2013-11-01

    Much like the host cells they infect, viruses must also regulate their life cycles. Herpes simples virus type 1 (HSV-1), a prominent human pathogen, uses a promoter-rich genome in conjunction with multiple viral trans-activating factors. Following entry into host cells, the virion-associated outer tegument proteins pUL46 and pUL47 act to increase expression of viral immediate-early (α) genes, thereby helping initiate the infection life cycle. Because pUL46 has gone largely unstudied, we employed a hybrid mass spectrometry-based approach to determine how pUL46 exerts its functions during early stages of infection. For a spatio-temporal characterization of pUL46, time-lapse microscopy was performed in live cells to define its dynamic localization from 2 to 24 h postinfection. Next, pUL46-containing protein complexes were immunoaffinity purified during infection of human fibroblasts and analyzed by mass spectrometry to investigate virus-virus and virus-host interactions, as well as post-translational modifications. We demonstrated that pUL46 is heavily phosphorylated in at least 23 sites. One phosphorylation site matched the consensus 14-3-3 phospho-binding motif, consistent with our identification of 14-3-3 proteins and host and viral kinases as specific pUL46 interactions. Moreover, we determined that pUL46 specifically interacts with the viral E3 ubiquitin ligase ICP0. We demonstrated that pUL46 is partially degraded in a proteasome-mediated manner during infection, and that the catalytic activity of ICP0 is responsible for this degradation. This is the first evidence of a viral protein being targeted for degradation by another viral protein during HSV-1 infection. Together, these data indicate that pUL46 levels are tightly controlled and important for the temporal regulation of viral gene expression throughout the virus life cycle. The concept of a structural virion protein, pUL46, performing nonstructural roles is likely to reflect a theme common to many viruses

  18. Track reconstruction in the emulsion-lead target of the OPERA experiment using the ESS microscope

    Science.gov (United States)

    Arrabito, L.; Bozza, C.; Buontempo, S.; Consiglio, L.; Cozzi, M.; D'Ambrosio, N.; DeLellis, G.; DeSerio, M.; Di Capua, F.; Di Ferdinando, D.; Di Marco, N.; Ereditato, A.; Esposito, L. S.; Fini, R. A.; Giacomelli, G.; Giorgini, M.; Grella, G.; Ieva, M.; Janicsko Csathy, J.; Juget, F.; Kreslo, I.; Laktineh, I.; Manai, K.; Mandrioli, G.; Marotta, A.; Migliozzi, P.; Monacelli, P.; Moser, U.; Muciaccia, M. T.; Pastore, A.; Patrizii, L.; Petukhov, Y.; Pistillo, C.; Pozzato, M.; Romano, G.; Rosa, G.; Russo, A.; Savvinov, N.; Schembri, A.; Scotto Lavina, L.; Simone, S.; Sioli, M.; Sirignano, C.; Sirri, G.; Strolin, P.; Tioukov, V.; Waelchli, T.

    2007-05-01

    The OPERA experiment, designed to conclusively prove the existence of νμ→ντ oscillations in the atmospheric sector, makes use of a massive lead-nuclear emulsion target to observe the appearance of ντ's in the CNGS νμ beam. The location and analysis of the neutrino interactions in quasi real-time required the development of fast computer-controlled microscopes able to reconstruct particle tracks with sub-micron precision and high efficiency at a speed of ~20 cm2/h. This paper describes the performance in particle track reconstruction of the European Scanning System, a novel automatic microscope for the measurement of emulsion films developed for OPERA.

  19. Track reconstruction in the emulsion-lead target of the OPERA experiment using the ESS microscope

    International Nuclear Information System (INIS)

    Arrabito, L; Bozza, C; Buontempo, S

    2007-01-01

    The OPERA experiment, designed to conclusively prove the existence of ν μ →ν τ oscillations in the atmospheric sector, makes use of a massive lead-nuclear emulsion target to observe the appearance of ν τ 's in the CNGS ν μ beam. The location and analysis of the neutrino interactions in quasi real-time required the development of fast computer-controlled microscopes able to reconstruct particle tracks with sub-micron precision and high efficiency at a speed of ∼20 cm 2 /h. This paper describes the performance in particle track reconstruction of the European Scanning System, a novel automatic microscope for the measurement of emulsion films developed for OPERA

  20. Bremsstrahlung from Relativistic Heavy Ions in a Fixed Target Experiment at the LHC

    International Nuclear Information System (INIS)

    Mikkelsen, Rune E.; Uggerhøj, Ulrik I.; Sørensen, Allan H.

    2015-01-01

    We calculate the emission of bremsstrahlung from lead and argon ions in ultraperipheral collisions in a fixed target experiment (AFTER) that uses the LHC beams. With nuclear charges of Ze equal to 82e and 18e, respectively, these ions are accelerated to energies of 7 Tev × Z. The bremsstrahlung peaks around ≈100 GeV and the spectrum exposes the nuclear structure of the incoming ion. The peak structure is significantly different from the flat power spectrum pertaining to a point charge. Photons are predominantly emitted within an angle of 1/γ to the direction of ion propagation. Our calculations are based on the Weizsäcker-Williams method of virtual quanta with application of existing experimental data on photonuclear interactions.

  1. Deeply Virtual Compton Scattering off a deuterium target at the HERMES experiment

    Energy Technology Data Exchange (ETDEWEB)

    Movsisyan, Aram

    2011-05-15

    Deeply virtual Compton scattering is studied in this report, using all data collected at the HERMES experiment from 1996 to 2005. Azimuthal asymmetries with respect to beam-helicity, beam-charge and target polarization alone and also to their different combinations for hard exclusive electroproduction of real photons in deep-inelastic scattering from a both unpolarized and longitudinally polarized deuterium targets are measured. The asymmetries are attributed to the interference between the deeply virtual Compton scattering and Bethe-Heitler processes. The asymmetries are observed in the exclusive region -(1.5){sup 2} GeV{sup 2}target, the leading Fourier amplitude of the beam-helicity asymmetry that is sensitive to the interference term is found to be substantial, but no significant t dependence is observed. The leading amplitude of the beam-charge asymmetry is substantial at large -t, but becomes small at small values of -t. The amplitudes of the beam-helicity asymmetry that are sensitive to the squared DVCS term are found to be consistent with zero. The deuteron Compton form factor H{sub 1} appears to have a similar behavior as H of the proton. (orig.)

  2. Conception and fabrication of innovative Am-Based targets: the ca mix/Cochix experiment

    International Nuclear Information System (INIS)

    Schmidt, N.; Croixmarie, Y.; Abonneau, E.; Ottaviani, J.P.; Donnet, L.; Desmouliere, F.; Konings, R.J.M.; Fernandez, A.

    2003-01-01

    A large experimental programme has been planned to be carried out in the French PHENIX reactor. The purpose is to evaluate the technical feasibility of minor actinide transmutation in fast reactors. Two major series of experiments have been designed for the heterogeneous transmutation mode. The first one, the MATINA (Matrices for Incineration of Actinides) series, aims at testing both different inert matrices in a fast flux and different concepts. The study is generic and focuses on the material behaviour under representative irradiation conditions. Targets are free of minor actinides to make the fabrication and design steps easier and faster. The second one, ECRIX, CAMIX (Compounds of Americium in PHENIX) and COCHIX (Concept Optimized microstructure in PHENIX), is a further step in the demonstration phase of the ''once-through'' transmutation and deals with Am-bearing targets irradiated in a fast neutron spectrum ''locally'' moderated. The moderator materials tested will be calcium hydride CaH 2-x (cases of ECRIX-H, CAMIX and COCHIX) and boron carbide 11 B 4 C (case of ECRIX-B) in order to accelerate the process of transmutation significantly. (author)

  3. The polarized atomic-beam target for the EDDA experiment and the time-reversal invariance test at COSY

    International Nuclear Information System (INIS)

    Eversheim, P.D.; Altmeier, M.; Felden, O.

    1996-01-01

    For the the EDDA experiment, which was set up to measure the p-vector - p-vector excitation function during the acceleration ramp of the cooler synchrotron COSY at Juelich, a polarized atomic-beam target was designed regarding the restrictions imposed by the geometry of the EDDA detector. Later, when the time-reversal invariance experiment is to be performed, the EDDA detector will serve as efficient internal polarimeter and the source has to deliver tensor polarized deuterons. The modular design of this polarized atomic-beam target that allows to meet these conditions are discussed in comparison to other existing polarized atomic-beam targets. (orig.)

  4. The polarized atomic-beam target for the EDDA experiment and the time-reversal invariance test at COSY

    Science.gov (United States)

    Eversheim, P. D.; Altmeier, M.; Felden, O.

    1997-02-01

    For the the EDDA experiment, which was set up to measure the p¯-p¯ excitation function during the acceleration ramp of the cooler synchrotron COSY at Jülich, a polarized atomic-beam target was designed regarding the restrictions imposed by the geometry of the EDDA detector. Later, when the time-reversal invariance experiment is to be performed, the EDDA detector will serve as efficient internal polarimeter and the source has to deliver tensor polarized deuterons. The modular design of this polarized atomic-beam target that allows to meet these conditions will be discussed in comparison to other existing polarized atomic-beam targets.

  5. Development of Detector Systems for Internal and Fixed Target Heavy Ion Physics Experiments

    International Nuclear Information System (INIS)

    Golubev, Pavel

    2003-04-01

    This thesis deals with intermediate energy heavy ion reactions with the particular aim to study the nuclear matter equation of state which defines the relation between statistical parameters of a fermionic system. The development of equipment for two experiments, CA47 at The Svedberg Laboratory in Uppsala, Sweden and R16 at Kernfysisch Versneller Inst. (KVI), Groningen, The Netherlands, are described. CA47 contains the CHICSi detector, a modular, ultra-high vacuum (UHV) compatible, multi-detector system, covering a solid angle of 3pi sr around the collision point. Together with two auxiliary detector systems CHICSi is placed at the cluster-jet target chamber of the CELSIUS storage ring. This thesis gives a technical overview of the detector and the development carried out in order to achieve the desired detection performance. Some laboratory and in-beam tests are described and the analysis of the first experimental results is discussed. The nuclear intensity interferometry experiment (R16) was performed in a dedicated beam-line of the AGOR superconducting cyclotron. Small-angle two-particle correlations were measured for the E/A = 61 MeV 36 Ar + 27 Al, 112 Sn, 124 Sn reactions, together with singles spectra. The experimental energy distributions of neutrons and light charged particles for the 36 Ar + 27 Al reaction have been analyzed with a Maxwellian multi-source prescription. These results, together with correlation function data, are used to extract information on the size of the emitting sources and their time evolution

  6. A polarized hydrogen/deuterium atomic beam source for internal target experiments

    International Nuclear Information System (INIS)

    Szczerba, D.; Buuren, L.D. van; Brand, J.F.J. van den; Bulten, H.J.; Ferro-Luzzi, M.; Klous, S.; Kolster, H.; Lang, J.; Mul, F.; Poolman, H.R.; Simani, M.C.

    2000-01-01

    A high-brightness hydrogen/deuterium atomic beam source is presented. The apparatus, previously used in electron scattering experiments with tensor-polarized deuterium (Ferro-Luzzi et al., Phys. Rev. Lett. 77 (1996) 2630; van den Brand et al., Phys. Rev. Lett. 78 (1997) 1235; Zhou et al., Phys. Rev. Lett. 82 (1998) 687; Bouwhuis et al., Phys. Rev. Lett. 82 (1999) 3755), was configured as a source for internal target experiments to measure single- and double-polarization observables, with either polarized hydrogen or vector/tensor polarized deuterium. The atomic beam intensity was enhanced by a factor of ∼2.5 by optimizing the Stern-Gerlach focusing system using high tip-field (∼1.5 T) rare-earth permanent magnets, and by increasing the pumping speed in the beam-formation chamber. Fluxes of (5.9±0.2)x10 16 1 H/s were measured in a diameter 12 mmx122 mm compression tube with its entrance at a distance of 27 cm from the last focusing element. The total output flux amounted to (7.6±0.2)x10 16 1 H/s

  7. Proteomic analyses of host and pathogen responses during bovine mastitis.

    Science.gov (United States)

    Boehmer, Jamie L

    2011-12-01

    The pursuit of biomarkers for use as clinical screening tools, measures for early detection, disease monitoring, and as a means for assessing therapeutic responses has steadily evolved in human and veterinary medicine over the past two decades. Concurrently, advances in mass spectrometry have markedly expanded proteomic capabilities for biomarker discovery. While initial mass spectrometric biomarker discovery endeavors focused primarily on the detection of modulated proteins in human tissues and fluids, recent efforts have shifted to include proteomic analyses of biological samples from food animal species. Mastitis continues to garner attention in veterinary research due mainly to affiliated financial losses and food safety concerns over antimicrobial use, but also because there are only a limited number of efficacious mastitis treatment options. Accordingly, comparative proteomic analyses of bovine milk have emerged in recent years. Efforts to prevent agricultural-related food-borne illness have likewise fueled an interest in the proteomic evaluation of several prominent strains of bacteria, including common mastitis pathogens. The interest in establishing biomarkers of the host and pathogen responses during bovine mastitis stems largely from the need to better characterize mechanisms of the disease, to identify reliable biomarkers for use as measures of early detection and drug efficacy, and to uncover potentially novel targets for the development of alternative therapeutics. The following review focuses primarily on comparative proteomic analyses conducted on healthy versus mastitic bovine milk. However, a comparison of the host defense proteome of human and bovine milk and the proteomic analysis of common veterinary pathogens are likewise introduced.

  8. Progress on the HUPO Draft Human Proteome: 2017 Metrics of the Human Proteome Project.

    Science.gov (United States)

    Omenn, Gilbert S; Lane, Lydie; Lundberg, Emma K; Overall, Christopher M; Deutsch, Eric W

    2017-12-01

    The Human Proteome Organization (HUPO) Human Proteome Project (HPP) continues to make progress on its two overall goals: (1) completing the protein parts list, with an annual update of the HUPO draft human proteome, and (2) making proteomics an integrated complement to genomics and transcriptomics throughout biomedical and life sciences research. neXtProt version 2017-01-23 has 17 008 confident protein identifications (Protein Existence [PE] level 1) that are compliant with the HPP Guidelines v2.1 ( https://hupo.org/Guidelines ), up from 13 664 in 2012-12 and 16 518 in 2016-04. Remaining to be found by mass spectrometry and other methods are 2579 "missing proteins" (PE2+3+4), down from 2949 in 2016. PeptideAtlas 2017-01 has 15 173 canonical proteins, accounting for nearly all of the 15 290 PE1 proteins based on MS data. These resources have extensive data on PTMs, single amino acid variants, and splice isoforms. The Human Protein Atlas v16 has 10 492 highly curated protein entries with tissue and subcellular spatial localization of proteins and transcript expression. Organ-specific popular protein lists have been generated for broad use in quantitative targeted proteomics using SRM-MS or DIA-SWATH-MS studies of biology and disease.

  9. Proteomics - new analytical approaches

    International Nuclear Information System (INIS)

    Hancock, W.S.

    2001-01-01

    Full text: Recent developments in the sequencing of the human genome have indicated that the number of coding gene sequences may be as few as 30,000. It is clear, however, that the complexity of the human species is dependent on the much greater diversity of the corresponding protein complement. Estimates of the diversity (discrete protein species) of the human proteome range from 200,000 to 300,000 at the lower end to 2,000,000 to 3,000,000 at the high end. In addition, proteomics (the study of the protein complement to the genome) has been subdivided into two main approaches. Global proteomics refers to a high throughput examination of the full protein set present in a cell under a given environmental condition. Focused proteomics refers to a more detailed study of a restricted set of proteins that are related to a specified biochemical pathway or subcellular structure. While many of the advances in proteomics will be based on the sequencing of the human genome, de novo characterization of protein microheterogeneity (glycosylation, phosphorylation and sulfation as well as the incorporation of lipid components) will be required in disease studies. To characterize these modifications it is necessary to digest the protein mixture with an enzyme to produce the corresponding mixture of peptides. In a process analogous to sequencing of the genome, shot-gun sequencing of the proteome is based on the characterization of the key fragments produced by such a digest. Thus, a glycopeptide and hence a specific glycosylation motif will be identified by a unique mass and then a diagnostic MS/MS spectrum. Mass spectrometry will be the preferred detector in these applications because of the unparalleled information content provided by one or more dimensions of mass measurement. In addition, highly efficient separation processes are an absolute requirement for advanced proteomic studies. For example, a combination of the orthogonal approaches, HPLC and HPCE, can be very powerful

  10. Proteomics Insights into Autophagy.

    Science.gov (United States)

    Cudjoe, Emmanuel K; Saleh, Tareq; Hawkridge, Adam M; Gewirtz, David A

    2017-10-01

    Autophagy, a conserved cellular process by which cells recycle their contents either to maintain basal homeostasis or in response to external stimuli, has for the past two decades become one of the most studied physiological processes in cell biology. The 2016 Nobel Prize in Medicine and Biology awarded to Dr. Ohsumi Yoshinori, one of the first scientists to characterize this cellular mechanism, attests to its importance. The induction and consequent completion of the process of autophagy results in wide ranging changes to the cellular proteome as well as the secretome. MS-based proteomics affords the ability to measure, in an unbiased manner, the ubiquitous changes that occur when autophagy is initiated and progresses in the cell. The continuous improvements and advances in mass spectrometers, especially relating to ionization sources and detectors, coupled with advances in proteomics experimental design, has made it possible to study autophagy, among other process, in great detail. Innovative labeling strategies and protein separation techniques as well as complementary methods including immuno-capture/blotting/staining have been used in proteomics studies to provide more specific protein identification. In this review, we will discuss recent advances in proteomics studies focused on autophagy. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  11. Translational plant proteomics: A perspective

    NARCIS (Netherlands)

    Agrawal, G.K.; Pedreschi, R.; Barkla, B.J.; Bindschedler, L.V.; Cramer, R.; Sarkar, A.; Renaut, J.; Job, D.; Rakwal, R.

    2012-01-01

    Translational proteomics is an emerging sub-discipline of the proteomics field in the biological sciences. Translational plant proteomics aims to integrate knowledge from basic sciences to translate it into field applications to solve issues related but not limited to the recreational and economic

  12. Development of surface perturbation target and thin silicon foil target used to research Rayleigh-Taylor instability in inertial confinement fusion experiment

    International Nuclear Information System (INIS)

    Zhou Bin; Sun Qi; Huang Yaodong; Shen Jun; Wu Guangming; Wang Jue

    2004-01-01

    The developments of the surface perturbation target and the thin silicon foil target used to research Rayleigh-Taylor instability in the resolved experiments of Inertial Confinement Fusion (ICF) are carried out. Based on the laser interference process combined with the figure-transfer process, the surface perturbation target with sine modulated perturbation is gotten, the wavelength is in the range of 20-100 μm and the amplitude is several micrometers. The thin silicon foil within the thickness about 3-4 μm is prepared by semiconductor process together with heavy-doped self-stop etching. Combined with ion beam etching, the check or the stripe patterns are transferred to the surface of thin silicon foils, and then the silicon grating foil is obtained

  13. Letter of Intent for a Drell-Yan Experiment with a Polarized Proton Target

    International Nuclear Information System (INIS)

    Geesaman, D.; Reimer, P.; Brown, C.; Christian, D.; Diefenthaler, M.; Peng, J.C.; Chang, W.C.; Chen, Y.C.; Sawada, S.; Chang, T.H.; Huang, J.; Jiang, X.; Leitch, M.; Klein, A.; Liu, K.; Liu, M.; McGaughey, P.; Beise, E.; Nakahara, K.; Aidala, C.; Lorenzon, W.; Raymond, R.; Badman, T.; Long, E.; Slifer, K.; Zielinski, R.; Guo, R.S.; Goto, Y.; El Fassi, L.; Myers, K.; Ransome, R.; Tadepalli, A.; Tice, B.; Chen, J.P.; Nakano, K.; Shibata, T.A.; Crabb, D.; Day, D.; Keller, D.; Rondon, O.

    2014-01-01

    It is well known that the proton is a spin-1/2 particle, but how the constituents (quarks and gluons) assemble to this quantized spin is still a mystery. There is a worldwide effort to map out the individual contributions to the proton spin. It is established that the quark spins contribute around 30%, while the gluon intrinsic angular momentum is still under active investigation at the Relativistic Heavy Ion Collider. Fully resolving the proton spin puzzle requires information on the orbital angular momentum (OAM) of both quarks and gluons. Recent studies have shown that the so-called transverse momentum-dependent parton distribution functions (TMDs) can inform us about the OAM of the partons. One of the most important TMDs, and the main focus of this LOI, is the so-called Sivers function. To summarize, we propose to make the first measurement of the Sivers function of sea quarks, which is expected to be non-zero if the sea quarks contribute orbital angular momentum to the proton spin, as expected from the pion cloud model, which also partially explains the E866 results. Thus, we will be able to deduce whether or not sea quark orbital motion contributes significantly to the proton spin. Specifically, we will determine the contribution from the anti-up quarks, with Bjorken-x in the range of ~ 0.1 to 0.5. Drell-Yan production off a polarized proton target has never been measured, and is complementary to the recently approved (stage-1) experiment E1027 at Fermilab, which will measure the Sivers function of the valence quarks using a polarized proton beam on an unpolarized proton target. If the measured sea quark Sivers function is non-zero, we will also determine its sign.

  14. Proteomics in uveal melanoma.

    LENUS (Irish Health Repository)

    Ramasamy, Pathma

    2014-01-01

    Uveal melanoma is the most common primary intraocular malignancy in adults, with an incidence of 5-7 per million per year. It is associated with the development of metastasis in about 50% of cases, and 40% of patients with uveal melanoma die of metastatic disease despite successful treatment of the primary tumour. The survival rates at 5, 10 and 15 years are 65%, 50% and 45% respectively. Unlike progress made in many other areas of cancer, uveal melanoma is still poorly understood and survival rates have remained similar over the past 25 years. Recently, advances made in molecular genetics have improved our understanding of this disease and stratification of patients into low risk and high risk for developing metastasis. However, only a limited number of studies have been performed using proteomic methods. This review will give an overview of various proteomic technologies currently employed in life sciences research, and discuss proteomic studies of uveal melanoma.

  15. Establishing Substantial Equivalence: Proteomics

    Science.gov (United States)

    Lovegrove, Alison; Salt, Louise; Shewry, Peter R.

    Wheat is a major crop in world agriculture and is consumed after processing into a range of food products. It is therefore of great importance to determine the consequences (intended and unintended) of transgenesis in wheat and whether genetically modified lines are substantially equivalent to those produced by conventional plant breeding. Proteomic analysis is one of several approaches which can be used to address these questions. Two-dimensional PAGE (2D PAGE) remains the most widely available method for proteomic analysis, but is notoriously difficult to reproduce between laboratories. We therefore describe methods which have been developed as standard operating procedures in our laboratory to ensure the reproducibility of proteomic analyses of wheat using 2D PAGE analysis of grain proteins.

  16. Recent US target-physics-related research in heavy-ion inertial fusion: simulations for tamped targets and for disk experiments in accelerator test facilities

    International Nuclear Information System (INIS)

    Mark, J.W.K.

    1982-01-01

    Within the last few years, there have also appeared in the Heavy-Ion Fusion literature several studies of targets which have outer tampers. One-dimensional simulations indicate higher target gains with a judicious amount of tamping. But for these targets, a full investigation has not been carried through in regards to conservative criteria for fluid instabilities as well as reasonable imperfections in target fabrication and illumination symmetry which all affect target ignition and burn. Comparisons of these results with the gain survey of Part I would have to be performed with care. These calculations suggest that experiments relating to high temperature disk heating, as well as beam deposition, focusing and transport can be performed within the context of current design proposals for accelerator test-facilities. Since the test-facilities have lower ion kinetic energy and beam pulse power as compared to reactor drivers, we achieve high-beam intensities at the focal spot by using short focal distance and properly designed beam optics

  17. Development of Detector Systems for Internal and Fixed Target Heavy Ion Physics Experiments

    Energy Technology Data Exchange (ETDEWEB)

    Golubev, Pavel

    2003-04-01

    This thesis deals with intermediate energy heavy ion reactions with the particular aim to study the nuclear matter equation of state which defines the relation between statistical parameters of a fermionic system. The development of equipment for two experiments, CA47 at The Svedberg Laboratory in Uppsala, Sweden and R16 at Kernfysisch Versneller Inst. (KVI), Groningen, The Netherlands, are described. CA47 contains the CHICSi detector, a modular, ultra-high vacuum (UHV) compatible, multi-detector system, covering a solid angle of 3pi sr around the collision point. Together with two auxiliary detector systems CHICSi is placed at the cluster-jet target chamber of the CELSIUS storage ring. This thesis gives a technical overview of the detector and the development carried out in order to achieve the desired detection performance. Some laboratory and in-beam tests are described and the analysis of the first experimental results is discussed. The nuclear intensity interferometry experiment (R16) was performed in a dedicated beam-line of the AGOR superconducting cyclotron. Small-angle two-particle correlations were measured for the E/A = 61 MeV {sup 36}Ar + {sup 27}Al, {sup 112}Sn, {sup 124}Sn reactions, together with singles spectra. The experimental energy distributions of neutrons and light charged particles for the {sup 36}Ar + {sup 27}Al reaction have been analyzed with a Maxwellian multi-source prescription. These results, together with correlation function data, are used to extract information on the size of the emitting sources and their time evolution.

  18. Development of the jet-target system of the MAGIX experiment

    Energy Technology Data Exchange (ETDEWEB)

    Stephan, Aulenbacher [Institut fuer Kernphysik, JGU, Mainz (Germany); Collaboration: Magix/MESA-Collaboration

    2016-07-01

    Since the new accelerator MESA which will be built up in Mainz in the next years operates at low Energies (100 MeV), but at high beam currents (1 mA), a thin windowless target is required. Therefore the MAGIX collaboration is developing a Jet-Target. This target blasts a Gas-Jet perpendicular to the beam through the scattering chamber of MAGIX. This talk is about the development of this Target System.

  19. PROTEINCHALLENGE: Crowd sourcing in proteomics analysis and software development

    DEFF Research Database (Denmark)

    Martin, Sarah F.; Falkenberg, Heiner; Dyrlund, Thomas Franck

    2013-01-01

    , including arguments for community-wide open source software development and “big data” compatible solutions for the future. For the meantime, we have laid out ten top tips for data processing. With these at hand, a first large-scale proteomics analysis hopefully becomes less daunting to navigate.......However there is clearly a real need for robust tools, standard operating procedures and general acceptance of best practises. Thus we submit to the proteomics community a call for a community-wide open set of proteomics analysis challenges—PROTEINCHALLENGE—that directly target and compare data analysis workflows......In large-scale proteomics studies there is a temptation, after months of experimental work, to plug resulting data into a convenient—if poorly implemented—set of tools, which may neither do the data justice nor help answer the scientific question. In this paper we have captured key concerns...

  20. Proteomic approaches in cancer risk and response assessment.

    Science.gov (United States)

    Petricoin, Emanuel F; Liotta, Lance A

    2004-02-01

    Proteomics is more than just a list-generating exercise where increases or decreases in protein expression are identified. Proteomic technologies will ultimately characterize information-flow through the protein circuitry that interconnects the extracellular microenvironment to the serum or plasma macroenvironment through intracellular signaling systems and their control of gene transcription. The nature of this information can be a cause or a consequence of disease processes and how patients respond to therapy. Analysis of human cancer as a model for how proteomics can have an impact at the bedside can take advantage of several promising new proteomic technologies. These technologies are being developed for early detection and risk assessment, therapeutic targeting and patient-tailored therapy.

  1. The Redox Proteome*

    Science.gov (United States)

    Go, Young-Mi; Jones, Dean P.

    2013-01-01

    The redox proteome consists of reversible and irreversible covalent modifications that link redox metabolism to biologic structure and function. These modifications, especially of Cys, function at the molecular level in protein folding and maturation, catalytic activity, signaling, and macromolecular interactions and at the macroscopic level in control of secretion and cell shape. Interaction of the redox proteome with redox-active chemicals is central to macromolecular structure, regulation, and signaling during the life cycle and has a central role in the tolerance and adaptability to diet and environmental challenges. PMID:23861437

  2. High-velocity Penetration of Concrete Targets with Three Types of Projectiles: Experiments and Analysis

    Directory of Open Access Journals (Sweden)

    Shuang Zhang

    Full Text Available Abstract This study conducted high-velocity penetration experiments using conventional ogive-nose, double-ogive-nose, and grooved-tapered projectiles of approximately 2.5 kg and initial velocities between 1000 and 1360 m/s to penetrate or perforate concrete targets with unconfined compressive strengths of nominally 40MPa. The penetration performance data of these three types of projectiles with two different types of materials (i.e., AerMet100 and DT300 were obtained. The crater depth model considering both the projectile mass and the initial velocity was proposed based on the test results and a theoretical analysis. The penetration ability and the trajectory stability of these three projectile types were compared and analyzed accordingly. The results showed that, under these experimental conditions, the effects of these two different kinds of projectile materials on the penetration depth and mass erosion rate of projectile were not obvious. The existing models could not reflect the crater depths for projectiles of greater weights or higher velocities, whereas the new model established in this study was reliable. The double-ogive-nose has a certain effect of drag reduction. Thus, the double-ogive-nose projectile has a higher penetration ability than the conventional ogive-nose projectile. Meanwhile, the grooved-tapered projectile has a better trajectory stability, because the convex parts of tapered shank generated the restoring moment to stabilize the trajectory.

  3. Target Group Segmentation in the Horse Buyers' Market against the Background of Equestrian Experience.

    Science.gov (United States)

    Gille, Claudia; Kayser, Maike; Spiller, Achim

    2010-01-01

    Whereas in former times horses were reserved primarily for people involved in agriculture, elite equestrians or the military, nowadays equestrian sport has become an activity for people with a wide variety of backgrounds. However, as more and more people become involved with equestrian sport today, the knowledge concerning animal husbandry in general is diminishing due to an alienation from agricultural themes in modern societies. As a consequence, this development affects both riding ability and the appraisal of horses, especially with respect to the purchase of horses. In order to analyse which factors influence purchase decisions in the horse market in conjunction with equestrian experience, 739 horse riders were surveyed on their purchase behaviour in this study. Using cluster analysis, a typology was generated that provides a differentiated picture of the preferences of the various rider groups. Three clusters were distinguished: the "amateurs", the "experienced" and the "experts". Taking personal horse riding proficiency into account, it could be concluded that especially the "amateur" group required objective criteria for the evaluation of a horse they are considering purchasing. Alongside "measureable" qualities, such as previous showing success or the level of training of the horse, also other attributes such as the simple handling of the horse should be taken into consideration. As particularly the "amateur" group in equestrian sport is increasing in numbers, it is therefore advisable when preparing a horse for sale to align oneself to the needs of this customer segment in order to ensure an effective and targeted marketing of horses.

  4. Double-quarkonium production at a fixed-target experiment at the LHC (AFTER@LHC)

    CERN Document Server

    Lansberg, Jean-Philippe

    2015-01-01

    We present predictions for double-quarkonium production in the kinematical region relevant for the proposed fixed-target experiment using the LHC beams (dubbed as AFTER@LHC). These include all spin-triplet S -wave charmonium and bottomonium pairs, i.e. Psi(n_1S) + Psi(n_2S), Psi(n_1S) + Upsilon(m_1S) and Upsilon(m_1S) + Upsilon(m_2S ) with n_1,n_2 = 1,2 and m_1,m_2 = 1,2,3. We calculate the contributions from double-parton scatterings and single-parton scatterings. With an integrated luminosity of 20 fb-1 to be collected at AFTER@LHC, we find that the yields for double-charmonium production are large enough for differential distribution measurements. We discuss some differential distributions for J/Psi + J/Psi production, which can help to study the physics of double-parton and single-parton scatterings in a new energy range and which might also be sensitive to double intrinsic c-bar(c) coalescence at large negative Feynman x.

  5. Study of compact X-ray laser pumped by pulse-train laser. Double-target experiment

    International Nuclear Information System (INIS)

    Yamaguchi, Naohiro; Fujikawa, Chiemi; Hara, Tamio

    2000-01-01

    We have been developing a tabletop x-ray laser based on the recombination plasma scheme. An advanced experiment has been started to improve x-ray laser output substantially. Two 11-mm-long laser produced plasmas were produced so that their axis aligned into a line, the double-target configuration. X-ray intensity of the 15.47 nm transition line of the Li-like Al ion has been enhanced in the double-target configuration. (author)

  6. Account of magnetic field effects of polarized proton target on charged particle trajectories in experiments with magnetic spectrometers

    International Nuclear Information System (INIS)

    Telegin, Yu.N.; Ranyuk, Yu.N.; Karnaukhov, I.M.; Lukhanin, A.A.; Sporov, E.A.

    1980-01-01

    Some effects of the influence of magnetic field of a polarized proton target (PPT) on trajectories of secondary particles in experiments using magnetic spectrometers are considered. It is shown that these effects can be eliminated by the target shift relatively to the spectrometer rotation axis and variation of the spectrometer installation angle. Numerical calculations of the correction values were performed for emitted particle momenta of 100-800 MeB/s and working intensity of the H 0 magnetic field H 0 =27 kG. The influence of the PPT magnetic field on the functions of angular and energy resolution in the γp→π + n experiment is investigated. The results obtained can be used in experiments with a polarized proton target

  7. Proteomic analysis of protein phosphatase Z1 from Candida albicans.

    Directory of Open Access Journals (Sweden)

    Bernadett Márkus

    Full Text Available Protein phosphatase Z is a "novel type" fungus specific serine/threonine protein phosphatase. Previously our research group identified the CaPPZ1 gene in the opportunistic pathogen Candida albicans and reported that the gene deletion had several important physiological consequences. In order to reveal the protein targets and the associated mechanisms behind the functions of the phosphatase a proteomic method was adopted for the comparison of the cappz1 deletion mutant and the genetically matching QMY23 control strain. Proteins extracted from the control and deletion mutant strains were separated by two-dimensional gel electrophoresis and the protein spots were stained with RuBPS and Pro-Q Diamond in order to visualize the total proteome and the phosphoproteome, respectively. The alterations in spot intensities were determined by densitometry and were analysed with the Delta2D (Decodon software. Spots showing significantly different intensities between the mutant and control strains were excised from the gels and were digested with trypsin. The resulting peptides were identified by LC-MS/MS mass spectrometry. As many as 15 protein spots were found that exhibited significant changes in their intensity upon the deletion of the phosphatase and 20 phosphoproteins were identified in which the level of phosphorylation was modified significantly in the mutant. In agreement with previous findings we found that the affected proteins function in protein synthesis, oxidative stress response, regulation of morphology and metabolism. Among these proteins we identified two potential CaPpz1 substrates (Eft2 and Rpp0 that may regulate the elongation step of translation. RT-qPCR experiments revealed that the expression of the genes coding for the affected proteins was not altered significantly. Thus, the absence of CaPpz1 exerted its effects via protein synthesis/degradation and phosphorylation/dephosphorylation. In addition, our proteomics data strongly

  8. Proteomic analysis of protein phosphatase Z1 from Candida albicans

    Science.gov (United States)

    Pfliegler, Walter P.; Petrényi, Katalin; Boros, Enikő; Pócsi, István; Tőzsér, József; Dombrádi, Viktor

    2017-01-01

    Protein phosphatase Z is a “novel type” fungus specific serine/threonine protein phosphatase. Previously our research group identified the CaPPZ1 gene in the opportunistic pathogen Candida albicans and reported that the gene deletion had several important physiological consequences. In order to reveal the protein targets and the associated mechanisms behind the functions of the phosphatase a proteomic method was adopted for the comparison of the cappz1 deletion mutant and the genetically matching QMY23 control strain. Proteins extracted from the control and deletion mutant strains were separated by two-dimensional gel electrophoresis and the protein spots were stained with RuBPS and Pro-Q Diamond in order to visualize the total proteome and the phosphoproteome, respectively. The alterations in spot intensities were determined by densitometry and were analysed with the Delta2D (Decodon) software. Spots showing significantly different intensities between the mutant and control strains were excised from the gels and were digested with trypsin. The resulting peptides were identified by LC-MS/MS mass spectrometry. As many as 15 protein spots were found that exhibited significant changes in their intensity upon the deletion of the phosphatase and 20 phosphoproteins were identified in which the level of phosphorylation was modified significantly in the mutant. In agreement with previous findings we found that the affected proteins function in protein synthesis, oxidative stress response, regulation of morphology and metabolism. Among these proteins we identified two potential CaPpz1 substrates (Eft2 and Rpp0) that may regulate the elongation step of translation. RT-qPCR experiments revealed that the expression of the genes coding for the affected proteins was not altered significantly. Thus, the absence of CaPpz1 exerted its effects via protein synthesis/degradation and phosphorylation/dephosphorylation. In addition, our proteomics data strongly suggested a role for

  9. Exploring the Human Plasma Proteome for Humoral Mediators of Remote Ischemic Preconditioning - A Word of Caution

    Science.gov (United States)

    Helgeland, Erik; Breivik, Lars Ertesvåg; Vaudel, Marc; Svendsen, Øyvind Sverre; Garberg, Hilde; Nordrehaug, Jan Erik; Berven, Frode Steingrimsen; Jonassen, Anne Kristine

    2014-01-01

    Despite major advances in early revascularization techniques, cardiovascular diseases are still the leading cause of death worldwide, and myocardial infarctions contribute heavily to this. Over the past decades, it has become apparent that reperfusion of blood to a previously ischemic area of the heart causes damage in and of itself, and that this ischemia reperfusion induced injury can be reduced by up to 50% by mechanical manipulation of the blood flow to the heart. The recent discovery of remote ischemic preconditioning (RIPC) provides a non-invasive approach of inducing this cardioprotection at a distance. Finding its endogenous mediators and their operative mode is an important step toward increasing the ischemic tolerance. The release of humoral factor(s) upon RIPC was recently demonstrated and several candidate proteins were published as possible mediators of the cardioprotection. Before clinical applicability, these potential biomarkers and their efficiency must be validated, a task made challenging by the large heterogeneity in reported data and results. Here, in an attempt to reproduce and provide more experimental data on these mediators, we conducted an unbiased in-depth analysis of the human plasma proteome before and after RIPC. From the 68 protein markers reported in the literature, only 28 could be mapped to manually reviewed (Swiss-Prot) protein sequences. 23 of them were monitored in our untargeted experiment. However, their significant regulation could not be reproducibly estimated. In fact, among the 394 plasma proteins we accurately quantified, no significant regulation could be confidently and reproducibly assessed. This indicates that it is difficult to both monitor and reproduce published data from experiments exploring for RIPC induced plasma proteomic regulations, and suggests that further work should be directed towards small humoral factors. To simplify this task, we made our proteomic dataset available via ProteomeXchange, where

  10. Translational plant proteomics: a perspective.

    Science.gov (United States)

    Agrawal, Ganesh Kumar; Pedreschi, Romina; Barkla, Bronwyn J; Bindschedler, Laurence Veronique; Cramer, Rainer; Sarkar, Abhijit; Renaut, Jenny; Job, Dominique; Rakwal, Randeep

    2012-08-03

    Translational proteomics is an emerging sub-discipline of the proteomics field in the biological sciences. Translational plant proteomics aims to integrate knowledge from basic sciences to translate it into field applications to solve issues related but not limited to the recreational and economic values of plants, food security and safety, and energy sustainability. In this review, we highlight the substantial progress reached in plant proteomics during the past decade which has paved the way for translational plant proteomics. Increasing proteomics knowledge in plants is not limited to model and non-model plants, proteogenomics, crop improvement, and food analysis, safety, and nutrition but to many more potential applications. Given the wealth of information generated and to some extent applied, there is the need for more efficient and broader channels to freely disseminate the information to the scientific community. This article is part of a Special Issue entitled: Translational Proteomics. Copyright © 2012 Elsevier B.V. All rights reserved.

  11. An experiment to study CP violation in the B system using an internal target at the HERA proton ring

    International Nuclear Information System (INIS)

    Hofmann, W.

    1993-03-01

    A group of physicists centered around the ARGUS collaboration got interested in hadron accelerators as a prolific source of B hadrons. The group is presently studying the option of a major-B-physics experiment to be performed at the HERA proton storage ring in fixed target mode using an internal target. Basic goal of the experiment is the detection of CP violation in the 'gold plated' B 0 → J/Ψ K s decay mode, using a dedicated detector triggered on lepton pairs from J/Ψ decay. (orig./HSI)

  12. Proteomic approach to nanotoxicity.

    Science.gov (United States)

    Matysiak, Magdalena; Kapka-Skrzypczak, Lucyna; Brzóska, Kamil; Gutleb, Arno C; Kruszewski, Marcin

    2016-03-30

    In recent years a large number of engineered nanomaterials (NMs) have been developed with promising technical benefits for consumers and medical appliances. In addition to already known potentially advantageous biological properties (antibiotic, antifungal and antiviral activity) of NMs, many new medical applications of NMs are foreseen, such as drug carriers, contrast agents, radiopharmaceuticals and many others. However, there is increasing concern about potential environmental and health effects due to NMs exposure. An increasing body of evidence suggests that NMs may trigger undesirable hazardous interactions with biological systems with potential to generate harmful effects. In this review we summarized a current state of knowledge on the proteomics approaches to nanotoxicity, including protein corona formation, in vitro and in vivo effects of exposure to NMs on proteome of different classes of organisms, from bacteria and plants to mammals. The effects of NMs on the proteome of environmentally relevant organisms are also described. Despite the benefit that development of nanotechnology may bring to the society, there are still major gaps of knowledge on the influence of nanomaterials on human health and the environment. Thus, it seems necessary to conduct further interdisciplinary research to fill the knowledge gaps in NM toxicity, using more holistic approaches than offered by conventional biological techniques. “OMICS” techniques will certainly help researchers in this field. In this paper we summarized the current stage of knowledge of the effects of nanoparticles on the proteome of different organisms, including those commonly used as an environmentally relevant indicator organisms.

  13. Arabidopsis peroxisome proteomics

    Directory of Open Access Journals (Sweden)

    John D. Bussell

    2013-04-01

    Full Text Available The analytical depth of investigation of the peroxisomal proteome of the model plant Arabidopsis thaliana has not yet reached that of other major cellular organelles such as chloroplasts or mitochondria. This is primarily due to the difficulties associated with isolating and obtaining purified samples of peroxisomes from Arabidopsis. So far only a handful of research groups have been successful in obtaining such fractions. To make things worse, enriched peroxisome fractions frequently suffer from significant organellar contamination, lowering confidence in localization assignment of the identified proteins. As with other cellular compartments, identification of peroxisomal proteins forms the basis for investigations of the dynamics of the peroxisomal proteome. It is therefore not surprising that, in terms of functional analyses by proteomic means, there remains a considerable gap between peroxisomes and chloroplasts or mitochondria. Alternative strategies are needed to overcome the obstacle of hard-to-obtain organellar fractions. This will help to close the knowledge gap between peroxisomes and other organelles and provide a full picture of the physiological pathways shared between organelles. In this review we briefly summarize the status quo and discuss some of the methodological alternatives to classic organelle proteomic approaches.

  14. Xylem sap proteomics.

    Science.gov (United States)

    de Bernonville, Thomas Dugé; Albenne, Cécile; Arlat, Matthieu; Hoffmann, Laurent; Lauber, Emmanuelle; Jamet, Elisabeth

    2014-01-01

    Proteomic analysis of xylem sap has recently become a major field of interest to understand several biological questions related to plant development and responses to environmental clues. The xylem sap appears as a dynamic fluid undergoing changes in its proteome upon abiotic and biotic stresses. Unlike cell compartments which are amenable to purification in sufficient amount prior to proteomic analysis, the xylem sap has to be collected in particular conditions to avoid contamination by intracellular proteins and to obtain enough material. A model plant like Arabidopsis thaliana is not suitable for such an analysis because efficient harvesting of xylem sap is difficult. The analysis of the xylem sap proteome also requires specific procedures to concentrate proteins and to focus on proteins predicted to be secreted. Indeed, xylem sap proteins appear to be synthesized and secreted in the root stele or to originate from dying differentiated xylem cells. This chapter describes protocols to collect xylem sap from Brassica species and to prepare total and N-glycoprotein extracts for identification of proteins by mass spectrometry analyses and bioinformatics.

  15. Technology of solid-fuel-layer targets for laser-fusion experiments

    International Nuclear Information System (INIS)

    Musinski, D.L.; Henderson, T.M.; Pattinson, T.R.; Tarvin, J.A.

    1979-01-01

    An apparatus which produces uniform solid-fuel layers in glass-shell targets for laser irradiation is described. A low-power cw laser pulse is used to vaporize the fuel within a previously frozen target which is maintained in a cold-helium environment by a cryogenic shroud. The rapid refreezing that follows the pulse forms a uniform fuel layer on the inner surface of the glass shell. This apparatus and technique meet the restrictions imposed by the experimental target chamber. The method does not perturb the target position; nor does it preclude the usual diagnostic experimets since the shroud is retracted before the main laser pulse arrives. Successful laser irradiation and implosion of solid-fuel-layer targets at KMSF have confirmed the effectiveness and reliability of this system and extended the range of laser-target-interaction studies in the cryogenic regime

  16. Gothenburg Experience with At-211-MX35 for Targeting Ovarian Carcinomas

    International Nuclear Information System (INIS)

    Elgqvist, J.

    2009-01-01

    This review will cover the efforts in Gothenburg to evaluate the potential of 211 At radioimmunotherapy (RIT) in the treatment of small tumor deposits of ovarian cancer in the abdominal cavity. The lifetime risk of ovarian cancer is 1% - 2% in European and American women. Despite seemingly successful surgery followed by chemotherapy, most patients will relapse, most frequently in the abdominal cavity, and succumb to the disease. Despite newer systemic chemotherapy regimens, the outcome has not improved over the past decade. RIT with various β-emitters has displayed promising results, though an international Phase III study of 90Y-labeled antibody showed no improvement in time to relapse or survival. This disappointing result might be explained by the long range of β-emitters, which results in poor irradiation of tumors less than a few millimeters in size. In treating small tumors, the short range and high LET of α-emitters such as 211 At offer a significant advantage by more effectively irradiating targeted small cell clusters. The PET and Cyclotron Unit at Rigshospitalet in Copenhagen has regularly since ∼10 years delivered 211 At to the research group in Gothenburg led by Prof. Ragnar Hultborn and Prof. Lars Jacobsson. Astatine-211 is isolated from the irradiated target by dry distillation. The 211 At-labelling method gives stable radiochemical yields of 70% - 80% with the antibody conjugate's tumor-cell binding ability essentially preserved. The activity of an antibody batch of 0.1 - 0.5 mg is approximately 300 - 500 MBq, sufficient for extensive animal experiments or for treatment of one patient. The therapeutic effect has been studied in a series of experiments in vitro and in nude mice with intraperitoneal (i.p.) growth of microscopic ovarian cancer tumors. A number of parameters related to the injected antibody conjugate and stage of tumor growth have been investigated. Studies of toxic effects for bone-marrow, kidneys, and the peritoneal membrane

  17. Extreme Ultraviolet Imaging of Electron Heated Targets in Petawatt Laser Experiments

    International Nuclear Information System (INIS)

    Ma, T.; MacPhee, A.; Key, M.; Akli, K.; Mackinnon, A.; Chen, C.; Barbee, T.; Freeman, R.; King, J.; Link, A.; Offermann, D.; Ovchinnikov, V.; Patel, P.; Stephens, R.; VanWoerkom, L.; Zhang, B.; Beg, F.

    2007-01-01

    The study of the transport of electrons, and the flow of energy into a solid target or dense plasma, is instrumental in the development of fast ignition inertial confinement fusion. An extreme ultraviolet (XUV) imaging diagnostic at 256 eV and 68 eV provides information about heating and energy deposition within petawatt laser-irradiated targets. XUV images of several irradiated solid targets are presented

  18. Target Group Segmentation in the Horse Buyers’ Market against the Background of Equestrian Experience

    Science.gov (United States)

    GILLE, Claudia; KAYSER, Maike; SPILLER, Achim

    2011-01-01

    Whereas in former times horses were reserved primarily for people involved in agriculture, elite equestrians or the military, nowadays equestrian sport has become an activity for people with a wide variety of backgrounds. However, as more and more people become involved with equestrian sport today, the knowledge concerning animal husbandry in general is diminishing due to an alienation from agricultural themes in modern societies. As a consequence, this development affects both riding ability and the appraisal of horses, especially with respect to the purchase of horses. In order to analyse which factors influence purchase decisions in the horse market in conjunction with equestrian experience, 739 horse riders were surveyed on their purchase behaviour in this study. Using cluster analysis, a typology was generated that provides a differentiated picture of the preferences of the various rider groups. Three clusters were distinguished: the “amateurs”, the “experienced” and the “experts”. Taking personal horse riding proficiency into account, it could be concluded that especially the “amateur” group required objective criteria for the evaluation of a horse they are considering purchasing. Alongside “measureable” qualities, such as previous showing success or the level of training of the horse, also other attributes such as the simple handling of the horse should be taken into consideration. As particularly the “amateur” group in equestrian sport is increasing in numbers, it is therefore advisable when preparing a horse for sale to align oneself to the needs of this customer segment in order to ensure an effective and targeted marketing of horses. PMID:24833979

  19. Development of plasma targets for interaction experiments at Tokyo Institute of Technology

    International Nuclear Information System (INIS)

    Hosokai, T.; Miyamoto, S.; Ogawa, M.

    1996-01-01

    A plasma target of z-pinch discharge is developed to obtain a hydrogen plasma of density approaching 10 18 cm -3 . The target plasma has a duration of about 1 μs for an initial gas pressure of 80 Pa. Prior to the gas flow type of target, the z-pinch process of a gas-filled discharge tube was studied by comparison with a computer simulation. The behavior of the z pinch is understood in terms of the dynamics of a shock wave and a current boundary sheet. A laser-induced plasma is also examined as an alternative plasma target free from the plasma lens effect. (orig.)

  20. A polarized solid {sup 3}He target for neutron transmission experiments

    Energy Technology Data Exchange (ETDEWEB)

    Keith, C.D. [North Carolina State Univ., Raleigh, NC (United States)]|[Triangle Universities Nuclear Laboratory, Durham, NC 27708-0308 (United States); Gould, C.R. [North Carolina State Univ., Raleigh, NC (United States)]|[Triangle Universities Nuclear Laboratory, Durham, NC 27708-0308 (United States); Haase, D.G. [North Carolina State Univ., Raleigh, NC (United States)]|[Triangle Universities Nuclear Laboratory, Durham, NC 27708-0308 (United States); Huffman, P.R. [Duke University, Durham, NC 27708-0308 (United States)]|[Triangle Universities Nuclear Laboratory, Durham, NC 27708-0308 (United States); Roberson, N.R. [Duke University, Durham, NC 27708-0308 (United States)]|[Triangle Universities Nuclear Laboratory, Durham, NC 27708-0308 (United States); Seely, M.L. [North Carolina State Univ., Raleigh, NC (United States)]|[Triangle Universities Nuclear Laboratory, Durham, NC 27708-0308 (United States); Tornow, W. [Duke University, Durham, NC 27708-0308 (United States)]|[Triangle Universities Nuclear Laboratory, Durham, NC 27708-0308 (United States); Wilburn, W.S. [Duke University, Durham, NC 27708-0308 (United States)]|[Triangle Universities Nuclear Laboratory, Durham, NC 27708-0308 (United States)

    1995-04-01

    We describe the construction and operation of a solid {sup 3}He polarized nuclear target which we have used for measurements of the spin dependence of the n-{sup 3}He interaction at MeV energies. The target, which contains 0.4 mole of {sup 3}He was polarized to 38% at 12 mK in a field of 7 T. The target is suitable for nuclear physics measurements which are insensitive to the large magnetic field and produce beam heating of tenths of microwatts.We discuss refinements and paths to improved solid {sup 3}He targets at higher polarizations and lower fields. ((orig.)).

  1. From genomes to vaccines via the proteome

    Directory of Open Access Journals (Sweden)

    R Alan Wilson

    2004-08-01

    Full Text Available An effective vaccine against schistosomiasis mansoni would be a valuable control tool and the high levels of protection elicited in rodents and primates by radiation-attenuated cercariae provide proof of principle. A major obstacle to vaccine development is the difficulty of identifying the antigens that mediate protection, not least because of the size of the genome at 280Mb DNA encoding 14,000 to 20,000 genes. The technologies collectively called proteomics, including 2D electrophoresis, liquid chromatography and mass spectrometry, now permit any protein to be identified provided there is extensive DNA data, and preferably a genome sequence. Applied to soluble (cytosolic proteins from schistosomes, proteomics reveals the great similarity in composition between life cycle stages, with several WHO vaccine candidates amongst the most abundant constituents. The proteomic approach has been successfully applied to identify the secretions used by cercaria to penetrate host skin, the gut secretions of adult worms and the proteins exposed on the tegument surface. Soluble proteins can also be separated by 2D electrophoresis before western blotting to identify the full range of antigenic targets present in a parasite preparation. The next step is to discover which target proteins represent the weak points in the worm's defences.

  2. The quest of the human proteome and the missing proteins: digging deeper.

    Science.gov (United States)

    Reddy, Panga Jaipal; Ray, Sandipan; Srivastava, Sanjeeva

    2015-05-01

    view was to study the wider tissue range with multiple digesting enzymes and follow targeted proteomics workflow in particular. On the innovation trajectory from the proteomics laboratory to novel proteomics diagnostics and therapeutics in society, we will also need new conceptual frames for translation science and innovation strategy in proteomics. These will embody both technical as well as rigorous social science and humanities considerations to understand the correlates of the proteome from cell to society.

  3. Integrative analysis to select cancer candidate biomarkers to targeted validation

    Science.gov (United States)

    Heberle, Henry; Domingues, Romênia R.; Granato, Daniela C.; Yokoo, Sami; Canevarolo, Rafael R.; Winck, Flavia V.; Ribeiro, Ana Carolina P.; Brandão, Thaís Bianca; Filgueiras, Paulo R.; Cruz, Karen S. P.; Barbuto, José Alexandre; Poppi, Ronei J.; Minghim, Rosane; Telles, Guilherme P.; Fonseca, Felipe Paiva; Fox, Jay W.; Santos-Silva, Alan R.; Coletta, Ricardo D.; Sherman, Nicholas E.; Paes Leme, Adriana F.

    2015-01-01

    Targeted proteomics has flourished as the method of choice for prospecting for and validating potential candidate biomarkers in many diseases. However, challenges still remain due to the lack of standardized routines that can prioritize a limited number of proteins to be further validated in human samples. To help researchers identify candidate biomarkers that best characterize their samples under study, a well-designed integrative analysis pipeline, comprising MS-based discovery, feature selection methods, clustering techniques, bioinformatic analyses and targeted approaches was performed using discovery-based proteomic data from the secretomes of three classes of human cell lines (carcinoma, melanoma and non-cancerous). Three feature selection algorithms, namely, Beta-binomial, Nearest Shrunken Centroids (NSC), and Support Vector Machine-Recursive Features Elimination (SVM-RFE), indicated a panel of 137 candidate biomarkers for carcinoma and 271 for melanoma, which were differentially abundant between the tumor classes. We further tested the strength of the pipeline in selecting candidate biomarkers by immunoblotting, human tissue microarrays, label-free targeted MS and functional experiments. In conclusion, the proposed integrative analysis was able to pre-qualify and prioritize candidate biomarkers from discovery-based proteomics to targeted MS. PMID:26540631

  4. Possible interpretation of the scale invariance violation during a deep inelastic muons scattering experiment on an hadron target

    International Nuclear Information System (INIS)

    Salati, Pierre.

    1980-01-01

    The purpose of this work is to analyse the structure functions produced by a deep inelastic scattering experiment of muons upon a hadronic target. A non perturbative model is tested. In order to chek the quantum chromodynamics, the moments and the Altarelli-Parisi equations are used. The main result is the scaling parameter lambda [fr

  5. Feasibility of detecting B → h/sup plus/h/sup minus/ in a fixed-target experiment

    International Nuclear Information System (INIS)

    Peng, J.C.; Mishra, C.S.; Moss, J.M.; McGaughey, P.; Kapustinsky, J.

    1988-01-01

    We discuss a proposal to measure two-body, two-prong decays of neutral B mesons and Λ/sub b/ in an 800 GeV fixed-target experiment. We expect to obtain a large sample (/approximately/10 3 events) of these decays if the branching ratios are /approximately/5 /times/ 10/sup /minus/5/. 23 refs., 2 figs., 3 tabs

  6. The Proteome of Primary Prostate Cancer

    DEFF Research Database (Denmark)

    Iglesias-Gato, Diego; Wikström, Pernilla; Tyanova, Stefka

    2016-01-01

    for disease aggressiveness. DESIGN, SETTING, AND PARTICIPANTS: Mass spectrometry was used for genome-scale quantitative proteomic profiling of 28 prostate tumors (Gleason score 6-9) and neighboring nonmalignant tissue in eight cases, obtained from formalin-fixed paraffin-embedded prostatectomy samples. Two...... changes occurring during prostate cancer (PCa) initiation and progression can result in clinically relevant discoveries. OBJECTIVES: To study cellular processes altered in PCa using system-wide quantitative analysis of changes in protein expression in clinical samples and to identify prognostic biomarkers......BACKGROUND: Clinical management of the prostate needs improved prognostic tests and treatment strategies. Because proteins are the ultimate effectors of most cellular reactions, are targets for drug actions and constitute potential biomarkers; a quantitative systemic overview of the proteome...

  7. Lessons from the proteomic study of osteoarthritis.

    Science.gov (United States)

    Ruiz-Romero, Cristina; Fernández-Puente, Patricia; Calamia, Valentina; Blanco, Francisco J

    2015-08-01

    Osteoarthritis is the most common rheumatic pathology and one of the leading causes of disability worldwide. It is a very complex disease whose etiopathogenesis is not fully understood. Furthermore, there are serious limitations for its management, since it lacks specific and sensitive biomarkers for early diagnosis, prognosis and therapeutic monitoring. Proteomic approaches performed in the last few decades have contributed to the knowledge on the molecular mechanisms that participate in this pathology and they have also led to interesting panels of putative biomarker candidates. In the next few years, further efforts should be made for translating these findings into the clinical routines. It is expected that targeted proteomics strategies will be highly valuable for the verification and qualification of biomarkers of osteoarthritis.

  8. Application of Proteomics and Peptidomics to COPD

    Directory of Open Access Journals (Sweden)

    Girolamo Pelaia

    2014-01-01

    Full Text Available Chronic obstructive pulmonary disease (COPD is a complex disorder involving both airways and lung parenchyma, usually associated with progressive and poorly reversible airflow limitation. In order to better characterize the phenotypic heterogeneity and the prognosis of patients with COPD, there is currently an urgent need for discovery and validation of reliable disease biomarkers. Within this context, proteomic and peptidomic techniques are emerging as very valuable tools that can be applied to both systemic and pulmonary samples, including peripheral blood, induced sputum, exhaled breath condensate, bronchoalveolar lavage fluid, and lung tissues. Identification of COPD biomarkers by means of proteomic and peptidomic approaches can thus also lead to discovery of new molecular targets potentially useful to improve and personalize the therapeutic management of this widespread respiratory disease.

  9. Fabrication and testing of gas filled targets for large scale plasma experiments on Nova

    International Nuclear Information System (INIS)

    Stone, G.F.; Spragge, M.; Wallace, R.J.; Rivers, C.J.

    1995-01-01

    An experimental campaign on the Nova laser was started in July 1993 to study one st of target conditions for the point design of the National Ignition Facility (NIF). The targets were specified to investigate the current NIF target conditions--a plasma of ∼3 keV electron temperature and an electron density of ∼1.0 E + 21 cm -3 . A gas cell target design was chosen to confine as gas of ∼0.01 cm 3 in volume at ∼ 1 atmosphere. This paper will describe the major steps and processes necessary in the fabrication, testing and delivery of these targets for shots on the Nova Laser at LLNL

  10. Modelling of SOL flows and target asymmetries in JET field reversal experiments with EDGE2D code

    International Nuclear Information System (INIS)

    Chankin, A.; Coad, J.; Corrigan, G.

    1999-11-01

    The EDGE2D code with drifts can reproduce the main trends of target asymmetries observed in field reversal experiments. It also re-produces qualitatively the main feature of recent JET results obtained with double-sided reciprocating Langmuir probes introduced near the top of the torus: the reversal of parallel plasma flow with toroidal field reversal. The code results suggest that the major contributor to the observed target asymmetries is the co-current toroidal momentum generated inside the scrape-off layer (SOL) by j r xB forces due to the presence of large up-down pressure asymmetries. Contrary to previous expectations of the predominant role of ExB drifts in creating target asymmetries, ∇B and centrifugal drifts were found to be mainly responsible for both parallel flows and target asymmetries. (author)

  11. Proteomics Development and Application for Bioforensics

    Energy Technology Data Exchange (ETDEWEB)

    Wahl, Karen L.; Wunschel, David S.; Clowers, Brian H.

    2010-09-15

    Proteomics is a relatively new scientific discipline dedicated to the comprehensive study of the protein composition of biological systems. While genomic sequencing is an invaluable tool for bioforensic sample identification, proteomics complements genomics in that the genes present in an organism code for the proteins that can be present in a microorganism. Many proteins are conserved for general identification while other protein expression varies with environment/growth state/growth conditions (i.e. not all proteins are expressed at any given time or condition) providing additional information beyond genomic analysis. This expression specificity and the relative stability of proteins with respect to genetic material make them attractive targets for microorganism identification and forensic applications to complement genomic approaches. Proteomic analysis depends upon the availability of genome sequences of the relevant organisms or their near relatives. The known amino acid sequences for potential proteins within the database can be compared to amino acid sequences of actual proteins present in a sample as determined with high mass accuracy by mass spectrometry for identification of the proteins in the sample. With the development of technology for rapid genome sequencing of organisms, the known protein database is growing, supporting improved identification of the proteins present in a sample. Recent developments in mass spectrometry instrumentation and microbial sequencing are leading to an increased growth in application of proteomics to microbiology, pathogen detection, disease diagnosis and microbial forensics as well as other biological disciplines. Mass spectrometry analysis does not require a priori knowledge of the sample or expected targets to gain meaningful.

  12. International Experience with Key Program Elements of IndustrialEnergy Efficiency or Greenhouse Gas Emissions Reduction Target-SettingPrograms

    Energy Technology Data Exchange (ETDEWEB)

    Price, Lynn; Galitsky, Christina; Kramer, Klaas Jan

    2008-02-02

    Target-setting agreements, also known as voluntary ornegotiated agreements, have been used by a number of governments as amechanism for promoting energy efficiency within the industrial sector. Arecent survey of such target-setting agreement programs identified 23energy efficiency or GHG emissions reduction voluntary agreement programsin 18 countries. International best practice related to target-settingagreement programs calls for establishment of a coordinated set ofpolicies that provide strong economic incentives as well as technical andfinancial support to participating industries. The key program elementsof a target-setting program are the target-setting process,identification of energy-saving technologies and measures usingenergy-energy efficiency guidebooks and benchmarking as well as byconducting energy-efficiency audits, development of an energy-savingsaction plan, development and implementation of energy managementprotocols, development of incentives and supporting policies, monitoringprogress toward targets, and program evaluation. This report firstprovides a description of three key target-setting agreement programs andthen describes international experience with the key program elementsthat comprise such programs using information from the three keytarget-setting programs as well as from other international programsrelated to industrial energy efficiency or GHG emissionsreductions.

  13. Design and verification experiments for the windowless spallation target of the ADS prototype Myrrha

    International Nuclear Information System (INIS)

    Kantrien Van, Tichelen; Kupschus, P.; Arien, B.; Ait Abderrahim, H.

    2003-01-01

    SCKxCEN, the Belgian Nuclear Research Centre, works on the conceptual design and basic engineering of a multipurpose ADS for R and D, dubbed MYRRHA, a small high-performance irradiation facility with fast neutron fluxes up to 1.10 15 n/cm 2 /s to start operation in about 2010. Specific to the MYRRHA ADS system is the choice for a windowless spallation target at the centre of the subcritical core. Apart from the space limitations and material property short-comings, the current and power density figures would make the design of a solid window for the spallation source next to impossible: the chosen 5 mA at the relative low energy of 350 MeV leads to a current density of order 150 μA/cm 2 (as far as we know at least a factor of 3 higher than any window design that has been attempted to meet). This is the main reason for adopting the windowless design for MYRRHA which has as a consequence that the free surface ultimately has to be compatible with the vacuum requirements of the beam transport system of the accelerator. The total beam energy will be dumped into a volume of ca 0.5 1 leading to a heating power density of ca 3 kW/cm 3 . In order to remove this heat from the LM with an average temperature increase of 100 deg C on top of the temperature of the inlet flow of 240 deg C a total flow rate of 101/s at an average flow speed of 2.5 m/s is required. It is suggested from estimates that the evaporation from 'hot spots' with elevated temperatures beyond the average 340 deg C - close to the free surface in the re-circulation zone - is then still acceptable. The design investigations are therefore directed to assess and minimise the re-circulation zone inherent in the free surface formation under the geometry and flow requirements. This paper will summarize the design programme for the windowless design of the spallation source at the centre of the subcritical core. It will include the main findings reported in (Van Tichelen, 2000) and (Van Tichelen, 2001) and the

  14. Redox Proteomics and Platelet Activation: Understanding the Redox Proteome to Improve Platelet Quality for Transfusion

    Science.gov (United States)

    Sonego, Giona; Abonnenc, Mélanie; Tissot, Jean-Daniel; Prudent, Michel; Lion, Niels

    2017-01-01

    Blood banks use pathogen inactivation (PI) technologies to increase the safety of platelet concentrates (PCs). The characteristics of PI-treated PCs slightly differ from those of untreated PCs, but the underlying reasons are not well understood. One possible cause is the generation of oxidative stress during the PI process. This is of great interest since reactive oxygen species (ROS) act as second messengers in platelet functions. Furthermore, there are links between protein oxidation and phosphorylation, another mechanism that is critical for cell regulation. Current research efforts focus on understanding the underlying mechanisms and identifying new target proteins. Proteomics technologies represent powerful tools for investigating signaling pathways involving ROS and post-translational modifications such as phosphorylation, while quantitative techniques enable the comparison of the platelet resting state versus the stimulated state. In particular, redox cysteine is a key player in platelet activation upon stimulation by different agonists. This review highlights the experiments that have provided insights into the roles of ROS in platelet function and the implications for platelet transfusion, and potentially in diseases such as inflammation and platelet hyperactivity. The review also describes the implication of redox mechanism in platelet storage considerations. PMID:28208668

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

    Science.gov (United States)

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

    2013-12-16

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

  16. The Nike KrF laser facility: Performance and initial target experiments

    Science.gov (United States)

    Obenschain, S. P.; Bodner, S. E.; Colombant, D.; Gerber, K.; Lehmberg, R. H.; McLean, E. A.; Mostovych, A. N.; Pronko, M. S.; Pawley, C. J.; Schmitt, A. J.; Sethian, J. D.; Serlin, V.; Stamper, J. A.; Sullivan, C. A.; Dahlburg, J. P.; Gardner, J. H.; Chan, Y.; Deniz, A. V.; Hardgrove, J.; Lehecka, T.; Klapisch, M.

    1996-05-01

    Krypton-fluoride (KrF) lasers are of interest to laser fusion because they have both the large bandwidth capability (≳THz) desired for rapid beam smoothing and the short laser wavelength (1/4 μm) needed for good laser-target coupling. Nike is a recently completed 56-beam KrF laser and target facility at the Naval Research Laboratory. Because of its bandwidth of 1 THz FWHM (full width at half-maximum), Nike produces more uniform focal distributions than any other high-energy ultraviolet laser. Nike was designed to study the hydrodynamic instability of ablatively accelerated planar targets. First results show that Nike has spatially uniform ablation pressures (Δp/pNike laser in producing uniform illumination, and its performance in correspondingly uniform acceleration of targets.

  17. The potato tuber mitochondrial proteome

    DEFF Research Database (Denmark)

    Salvato, Fernanda; Havelund, Jesper Foged; Chen, Mingjie

    2014-01-01

    Mitochondria are called the powerhouses of the cell. To better understand the role of mitochondria in maintaining and regulating metabolism in storage tissues, highly purified mitochondria were isolated from dormant potato tubers (Solanum tuberosum 'Folva') and their proteome investigated. Proteins...... manner using normalized spectral counts including as many as 5-fold more "extreme" proteins (low mass, high isoelectric point, hydrophobic) than previous mitochondrial proteome studies. We estimate that this compendium of proteins represents a high coverage of the potato tuber mitochondrial proteome...

  18. LANL sunnyside experiment: Study of neutron production in accelerator-driven targets

    International Nuclear Information System (INIS)

    Morgan, G.; Butler, G.; Cappiello, M.; Carius, S.; Daemen, L.; DeVolder, B.; Frehaut, J.; Goulding, C.; Grace, R.; Green, R.; Lisowski, P.; Littleton, P.; King, J.; King, N.; Prael, R.; Stratton, T.; Turner, S.; Ullmann, J.; Venneri, F.; Yates, M.

    1995-01-01

    Measurements have been made of the neutron production in prototypic targets for accelerator driven systems. Studies were conducted on four target assemblies containing lead, lithium, tungsten, and a thorium-salt mixture. Integral data on total neutron production were obtained as well as more differential data on neutron leakage and neutron flux profiles in the blanket/moderator region. Data analysis on total neutron production is complete and shows excellent agreement with calculations using the LAHET/MCNP code system

  19. LANL sunnyside experiment: Study of neutron production in accelerator-driven targets

    Energy Technology Data Exchange (ETDEWEB)

    Morgan, G.; Butler, G.; Cappiello, M. [Los Alamos National Laboratory, NM (United States)] [and others

    1995-10-01

    Measurements have been made of the neutron production in prototypic targets for accelerator driven systems. Studies were conducted on four target assemblies containing lead, lithium, tungsten, and a thorium-salt mixture. Integral data on total neutron production were obtained as well as more differential data on neutron leakage and neutron flux profiles in the blanket/moderator region. Data analysis on total neutron production is complete and shows excellent agreement with calculations using the LAHET/MCNP code system.

  20. The path to enlightenment: making sense of genomic and proteomic information.

    Science.gov (United States)

    Maurer, Martin H

    2004-05-01

    Whereas genomics describes the study of genome, mainly represented by its gene expression on the DNA or RNA level, the term proteomics denotes the study of the proteome, which is the protein complement encoded by the genome. In recent years, the number of proteomic experiments increased tremendously. While all fields of proteomics have made major technological advances, the biggest step was seen in bioinformatics. Biological information management relies on sequence and structure databases and powerful software tools to translate experimental results into meaningful biological hypotheses and answers. In this resource article, I provide a collection of databases and software available on the Internet that are useful to interpret genomic and proteomic data. The article is a toolbox for researchers who have genomic or proteomic datasets and need to put their findings into a biological context.

  1. Uranium fluoride and metallic uranium as target materials for heavy-element experiments at SHIP

    Energy Technology Data Exchange (ETDEWEB)

    Kindler, Birgit [Gesellschaft fuer Schwerionenforschung (GSI), Planckstrasse 1, D-64291 Darmstadt (Germany)], E-mail: b.kindler@gsi.de; Ackermann, Dieter; Hartmann, Willi; Hessberger, Fritz Peter; Hofmann, Sigurd; Huebner, Annett; Lommel, Bettina; Mann, Rido; Steiner, Jutta [Gesellschaft fuer Schwerionenforschung (GSI), Planckstrasse 1, D-64291 Darmstadt (Germany)

    2008-06-01

    In this contribution we describe the production and application of uranium targets for synthesis of heavy elements. The targets are prepared from uranium fluoride (UF{sub 4}) and from metallic uranium with thin carbon foils as backing. Targets of UF{sub 4} were produced by thermal evaporation in a similar way as the frequently applied targets out of Bi, Bi{sub 2}O{sub 3}, Pb, PbS, SmF{sub 3}, and NdF{sub 3,} prepared mostly from isotopically enriched material [Birgit Kindler, et al., Nucl. Instr. and Meth. A 561 (2006) 107; Bettina Lommel, et al., Nucl. Instr. and Meth. A 561 (2006) 100]. In order to use more intensive beams and to avoid scattering of the reaction products in the target, metallic uranium is favorable. However, evaporation of metallic uranium is not feasible at a sustainable yield. Therefore, we established magnetron sputtering of metallic uranium. We describe production and properties of these targets. First irradiation tests show promising results.

  2. Experience gained with the 3D machining of the W7-X HHF divertor target elements

    International Nuclear Information System (INIS)

    Junghanns, P.; Boscary, J.; Peacock, A.

    2015-01-01

    Highlights: • The Wendelstein 7-X surface of the actively cooled divertor is built up of 890 individually 3D machined target elements. • To date 300 target elements have been 3D machined with an accuracy of ±0.015 mm. • Copper discovered on the surface of few elements is no risk to operation. - Abstract: The high heat flux (HHF) divertor of W7-X consists of 100 target modules assembled from 890 actively water-cooled target elements protected with CFC tiles. The divertor surface will be built up of individually 3D machined target elements with 89 individual element types. To date 300 of the 890 target elements have been 3D machined with a very good accuracy. To achieve this successful result, a prototyping phase has been conducted to qualify the manufacturing route and to define the acceptance criteria with measures taken to minimize the risk of unacceptable damage during the manufacturing. After the 3D-machining, during the incoming inspection, copper infiltration from the interface between the CFC tiles and the CuCrZr heat sink to the plasma facing surface was detected in a small number of elements.

  3. Universal Versus Targeted Screening for Lynch Syndrome: Comparing Ascertainment and Costs Based on Clinical Experience.

    Science.gov (United States)

    Erten, Mujde Z; Fernandez, Luca P; Ng, Hank K; McKinnon, Wendy C; Heald, Brandie; Koliba, Christopher J; Greenblatt, Marc S

    2016-10-01

    Strategies to screen colorectal cancers (CRCs) for Lynch syndrome are evolving rapidly; the optimal strategy remains uncertain. We compared targeted versus universal screening of CRCs for Lynch syndrome. In 2010-2011, we employed targeted screening (age Lynch syndrome and estimated the 5-year costs of preventing CRC by colonoscopy screening, using a system dynamics model. Using targeted screening, 51/175 (29 %) cancers fit criteria and were tested by immunohistochemistry; 15/51 (29 %, or 8.6 % of all CRCs) showed suspicious loss of ≥1 mismatch repair protein. Germline mismatch repair gene mutations were found in 4/4 cases sequenced (11 suspected cases did not have germline testing). Using universal screening, 17/292 (5.8 %) screened cancers had abnormal immunohistochemistry suspicious for Lynch syndrome. Germline mismatch repair mutations were found in only 3/10 cases sequenced (7 suspected cases did not have germline testing). The mean cost to identify Lynch syndrome probands was ~$23,333/case for targeted screening and ~$175,916/case for universal screening at our institution. Estimated costs to identify and screen probands and relatives were: targeted, $9798/case and universal, $38,452/case. In real-world Lynch syndrome management, incomplete clinical follow-up was the major barrier to do genetic testing. Targeted screening costs 2- to 7.5-fold less than universal and rarely misses Lynch syndrome cases. Future changes in testing costs will likely change the optimal algorithm.

  4. Water flow experiments and analyses on the cross-flow type mercury target model with the flow guide plates

    CERN Document Server

    Haga, K; Kaminaga, M; Hino, R

    2001-01-01

    A mercury target is used in the spallation neutron source driven by a high-intensity proton accelerator. In this study, the effectiveness of the cross-flow type mercury target structure was evaluated experimentally and analytically. Prior to the experiment, the mercury flow field and the temperature distribution in the target container were analyzed assuming a proton beam energy and power of 1.5 GeV and 5 MW, respectively, and the feasibility of the cross-flow type target was evaluated. Then the average water flow velocity field in the target mock-up model, which was fabricated from Plexiglass for a water experiment, was measured at room temperature using the PIV technique. Water flow analyses were conducted and the analytical results were compared with the experimental results. The experimental results showed that the cross-flow could be realized in most of the proton beam path area and the analytical result of the water flow velocity field showed good correspondence to the experimental results in the case w...

  5. Functional genomics and proteomics - the role of nuclear medicine

    Energy Technology Data Exchange (ETDEWEB)

    Haberkorn, U. [Heidelberg Univ. (Germany). Abt. fuer Klinische Nuklearmedizin; German Cancer Research Center, Heidelberg (Germany); Altmann, A. [German Cancer Research Center, Heidelberg (Germany); Eisenhut, M. [German Cancer Research Center, Heidelberg (Germany). Dept. of Radiopharmacy

    2002-01-01

    Now that the sequencing of the human genome has been completed, the basic challenges are finding the genes, locating their coding regions and predicting their functions. This will result in a new understanding of human biology as well as in the design of new molecular structures as potential novel diagnostic or drug discovery targets. The assessment of gene function may be performed using the tools of the genome program. These tools represent high-throughput methods used to evaluate changes in the expression of many or all genes of an organism at the same time in order to investigate genetic pathways for normal development and disease. This will lead to a shift in the scientific paradigm: In the pre-proteomics era, functional assignments were derived from hypothesis-driven experiments designed to understand specific cellular processes. The new tools describe proteins on a proteome-wide scale, thereby creating a new way of doing cell research which results in the determination of three-dimensional protein structures and the description of protein networks. These descriptions may then be used for the design of new hypotheses and experiments in the traditional physiological, biochemical and pharmacological sense. The evaluation of genetically manipulated animals or newly designed biomolecules will require a thorough understanding of physiology, biochemistry and pharmacology and the experimental approaches will involve many new technologies, including in vivo imaging with single-photon emission tomography and positron emission tomography. Nuclear medicine procedures may be applied for the determination of gene function and regulation using established and new tracers or using in vivo reporter genes such as enzymes, receptors, antigens or transporters. Pharmacogenomics will identify new surrogate markers for therapy monitoring which may represent potential new tracers for imaging. Also, drug distribution studies for new therapeutic biomolecules are needed, at least

  6. Functional genomics and proteomics - the role of nuclear medicine

    International Nuclear Information System (INIS)

    Haberkorn, U.; Altmann, A.; Eisenhut, M.

    2002-01-01

    Now that the sequencing of the human genome has been completed, the basic challenges are finding the genes, locating their coding regions and predicting their functions. This will result in a new understanding of human biology as well as in the design of new molecular structures as potential novel diagnostic or drug discovery targets. The assessment of gene function may be performed using the tools of the genome program. These tools represent high-throughput methods used to evaluate changes in the expression of many or all genes of an organism at the same time in order to investigate genetic pathways for normal development and disease. This will lead to a shift in the scientific paradigm: In the pre-proteomics era, functional assignments were derived from hypothesis-driven experiments designed to understand specific cellular processes. The new tools describe proteins on a proteome-wide scale, thereby creating a new way of doing cell research which results in the determination of three-dimensional protein structures and the description of protein networks. These descriptions may then be used for the design of new hypotheses and experiments in the traditional physiological, biochemical and pharmacological sense. The evaluation of genetically manipulated animals or newly designed biomolecules will require a thorough understanding of physiology, biochemistry and pharmacology and the experimental approaches will involve many new technologies, including in vivo imaging with single-photon emission tomography and positron emission tomography. Nuclear medicine procedures may be applied for the determination of gene function and regulation using established and new tracers or using in vivo reporter genes such as enzymes, receptors, antigens or transporters. Pharmacogenomics will identify new surrogate markers for therapy monitoring which may represent potential new tracers for imaging. Also, drug distribution studies for new therapeutic biomolecules are needed, at least

  7. Plant redox proteomics

    DEFF Research Database (Denmark)

    Navrot, Nicolas; Finnie, Christine; Svensson, Birte

    2011-01-01

    PTMs in regulating enzymatic activities and controlling biological processes in plants. Notably, proteins controlling the cellular redox state, e.g. thioredoxin and glutaredoxin, appear to play dual roles to maintain oxidative stress resistance and regulate signal transduction pathways via redox PTMs......In common with other aerobic organisms, plants are exposed to reactive oxygen species resulting in formation of post-translational modifications related to protein oxidoreduction (redox PTMs) that may inflict oxidative protein damage. Accumulating evidence also underscores the importance of redox....... To get a comprehensive overview of these types of redox-regulated pathways there is therefore an emerging interest to monitor changes in redox PTMs on a proteome scale. Compared to some other PTMs, e.g. protein phosphorylation, redox PTMs have received less attention in plant proteome analysis, possibly...

  8. PROTEOMICS in aquaculture

    DEFF Research Database (Denmark)

    Rodrigues, Pedro M.; Silva, Tomé S.; Dias, Jorge

    2012-01-01

    Over the last forty years global aquaculture presented a growth rate of 6.9% per annum with an amazing production of 52.5million tonnes in 2008, and a contribution of 43% of aquatic animal food for human consumption. In order to meet the world's health requirements of fish protein, a continuous...... growth in production is still expected for decades to come. Aquaculture is, though, a very competitive market, and a global awareness regarding the use of scientific knowledge and emerging technologies to obtain a better farmed organism through a sustainable production has enhanced the importance...... questions and the role of proteomics in their investigation, outlining the advantages, disadvantages and future challenges. A brief description of the proteomics technical approaches will be presented. Special focus will be on the latest trends related to the aquaculture production of fish with defined...

  9. Improved techniques for the analysis of experiments with polarized targets. [1 to 2 GeV/c, polarization

    Energy Technology Data Exchange (ETDEWEB)

    Barrelet, E.

    1975-06-01

    An experiment was performed at the Bevatron to measure the polarization in the reaction ..pi../sup -/p ..-->.. ..pi../sup 0/n from a polarized target, at beam momenta between 1 and 2 GeV/c. Concentration is placed on the original aspects of our analysis, in particular: the geometrical reconstruction of the elastic events; the use of the high analyzing power of the reaction studied to probe the polarization of the target in magnitude and distribution; a study of the statistical estimation of the polarization parameter; a detailed study of the quasielastic background. (JFP)

  10. Radiation physics of high power spallation targets. State of the art simulation methods and experiments, the 'European Spallation Source' (ESS)

    International Nuclear Information System (INIS)

    Filges, D.; Cloth, P.; Neef, R.D.; Schaal, H.

    1998-01-01

    Particle transport and nuclear interactions of planned high power spallation targets with GeV proton beams can be simulated using widely developed Monte Carlo transport methods. This includes available high energy radiation transport codes and systems for low energy, earlier developed for reactor physics and fusion technology. Monte Carlo simulation codes and applied methods are discussed. The capabilities of the world-wide existing state-of-the-art computer code systems are demonstrated. Results of computational studies for the 'European Spallation Source' (ESS) mercury high power target station are given. The needs for spallation related data and planned experiments are shown. (author)

  11. The plant mitochondrial proteome

    DEFF Research Database (Denmark)

    Millar, A.H.; Heazlewood, J.L.; Kristensen, B.K.

    2005-01-01

    The plant mitochondrial proteome might contain as many as 2000-3000 different gene products, each of which might undergo post-translational modification. Recent studies using analytical methods, such as one-, two- and three-dimensional gel electrophoresis and one- and two-dimensional liquid...... context to be defined for them. There are indications that some of these proteins add novel activities to mitochondrial protein complexes in plants....

  12. MUMAL: Multivariate analysis in shotgun proteomics using machine learning techniques

    Directory of Open Access Journals (Sweden)

    Cerqueira Fabio R

    2012-10-01

    thus the turn around time of MS-based experiments in proteomics, but also improves the information content with benefits of a higher proteome coverage. This improvement, for instance, increases the chance to identify important drug targets or biomarkers for drug development or molecular diagnostics.

  13. A Review: Proteomics in Retinal Artery Occlusion, Retinal Vein Occlusion, Diabetic Retinopathy and Acquired Macular Disorders.

    Science.gov (United States)

    Cehofski, Lasse Jørgensen; Honoré, Bent; Vorum, Henrik

    2017-04-28

    Retinal artery occlusion (RAO), retinal vein occlusion (RVO), diabetic retinopathy (DR) and age-related macular degeneration (AMD) are frequent ocular diseases with potentially sight-threatening outcomes. In the present review we discuss major findings of proteomic studies of RAO, RVO, DR and AMD, including an overview of ocular proteome changes associated with anti-vascular endothelial growth factor (VEGF) treatments. Despite the severe outcomes of RAO, the proteome of the disease remains largely unstudied. There is also limited knowledge about the proteome of RVO, but proteomic studies suggest that RVO is associated with remodeling of the extracellular matrix and adhesion processes. Proteomic studies of DR have resulted in the identification of potential therapeutic targets such as carbonic anhydrase-I. Proliferative diabetic retinopathy is the most intensively studied stage of DR. Proteomic studies have established VEGF, pigment epithelium-derived factor (PEDF) and complement components as key factors associated with AMD. The aim of this review is to highlight the major milestones in proteomics in RAO, RVO, DR and AMD. Through large-scale protein analyses, proteomics is bringing new important insights into these complex pathological conditions.

  14. New developments in cryo-targets for the external COSY experiments

    CERN Document Server

    Abdel-Samad, S; Kilian, K

    2002-01-01

    For cooling the liquid hydrogen/deuterium target from room temperature to the operating temperature (15 K/19 K) until recently a long solid copper heat conductor and a short heat pipe was used between cooling machine and the target cell. Recently, a new target version with metallic heat conductor of minimal length and a long gravity-assisted heat pipe section was constructed. The target material is used as a heat transport medium and high heat transfer is achieved by liquid-gas circulation. This design drastically reduces the weight of the system to less than 10 g in the 32 cm long standard geometry as compared with the previous copper heat conductors of 600 g. Uncontrollable secondary interactions are thus avoided. The cycle time of cooling down or heating up is reduced. The characteristics at steady-state operating conditions of the new 32 cm heat pipe-target system have been measured for hydrogen, deuterium, nitrogen and methane as the working fluids. Also successful was the development of a 2 m long heat ...

  15. The Nike KrF laser facility: Performance and initial target experiments

    International Nuclear Information System (INIS)

    Obenschain, S.P.; Bodner, S.E.; Colombant, D.; Gerber, K.; Lehmberg, R.H.; McLean, E.A.; Mostovych, A.N.; Pronko, M.S.; Pawley, C.J.; Schmitt, A.J.; Sethian, J.D.; Serlin, V.; Stamper, J.A.; Sullivan, C.A.; Dahlburg, J.P.; Gardner, J.H.; Chan, Y.; Deniz, A.V.; Hardgrove, J.; Lehecka, T.; Klapisch, M.

    1996-01-01

    Krypton-fluoride (KrF) lasers are of interest to laser fusion because they have both the large bandwidth capability (approx-gt THz) desired for rapid beam smoothing and the short laser wavelength (1/4 μm) needed for good laser endash target coupling. Nike is a recently completed 56-beam KrF laser and target facility at the Naval Research Laboratory. Because of its bandwidth of 1 THz FWHM (full width at half-maximum), Nike produces more uniform focal distributions than any other high-energy ultraviolet laser. Nike was designed to study the hydrodynamic instability of ablatively accelerated planar targets. First results show that Nike has spatially uniform ablation pressures (Δp/p<2%). Targets have been accelerated for distances sufficient to study hydrodynamic instability while maintaining good planarity. In this review we present the performance of the Nike laser in producing uniform illumination, and its performance in correspondingly uniform acceleration of targets. copyright 1996 American Institute of Physics

  16. Targeting indoor residual spraying for malaria using epidemiological data: a case study of the Zambia experience.

    Science.gov (United States)

    Pinchoff, Jessie; Larsen, David A; Renn, Silvia; Pollard, Derek; Fornadel, Christen; Maire, Mark; Sikaala, Chadwick; Sinyangwe, Chomba; Winters, Benjamin; Bridges, Daniel J; Winters, Anna M

    2016-01-06

    In Zambia and other sub-Saharan African countries affected by ongoing malaria transmission, indoor residual spraying (IRS) for malaria prevention has typically been implemented over large areas, e.g., district-wide, and targeted to peri-urban areas. However, there is a recent shift in some countries, including Zambia, towards the adoption of a more strategic and targeted IRS approach, in coordination with increased emphasis on universal coverage of long-lasting insecticidal nets (LLINs) and effective insecticide resistance management. A true targeted approach would deliver IRS to sub-district areas identified as high-risk, with the goal of maximizing the prevention of malaria cases and deaths. Together with the Government of the Republic of Zambia, a new methodology was developed applying geographic information systems and satellite imagery to support a targeted IRS campaign during the 2014 spray season using health management information system data. This case study focuses on the developed methodology while also highlighting the significant research gaps which must be filled to guide countries on the most effective strategy for IRS targeting in the context of universal LLIN coverage and evolving insecticide resistance.

  17. Proteomics Standards Initiative: Fifteen Years of Progress and Future Work.

    Science.gov (United States)

    Deutsch, Eric W; Orchard, Sandra; Binz, Pierre-Alain; Bittremieux, Wout; Eisenacher, Martin; Hermjakob, Henning; Kawano, Shin; Lam, Henry; Mayer, Gerhard; Menschaert, Gerben; Perez-Riverol, Yasset; Salek, Reza M; Tabb, David L; Tenzer, Stefan; Vizcaíno, Juan Antonio; Walzer, Mathias; Jones, Andrew R

    2017-12-01

    The Proteomics Standards Initiative (PSI) of the Human Proteome Organization (HUPO) has now been developing and promoting open community standards and software tools in the field of proteomics for 15 years. Under the guidance of the chair, cochairs, and other leadership positions, the PSI working groups are tasked with the development and maintenance of community standards via special workshops and ongoing work. Among the existing ratified standards, the PSI working groups continue to update PSI-MI XML, MITAB, mzML, mzIdentML, mzQuantML, mzTab, and the MIAPE (Minimum Information About a Proteomics Experiment) guidelines with the advance of new technologies and techniques. Furthermore, new standards are currently either in the final stages of completion (proBed and proBAM for proteogenomics results as well as PEFF) or in early stages of design (a spectral library standard format, a universal spectrum identifier, the qcML quality control format, and the Protein Expression Interface (PROXI) web services Application Programming Interface). In this work we review the current status of all of these aspects of the PSI, describe synergies with other efforts such as the ProteomeXchange Consortium, the Human Proteome Project, and the metabolomics community, and provide a look at future directions of the PSI.

  18. Capture reactions at astrophysically relevant energies: extended gas target experiments and GEANT simulations

    CERN Document Server

    Kölle, V; Braitmayer, S E; Mohr, P J; Wilmes, S; Staudt, G; Hammer, J W; Jäger, M; Knee, H; Kunz, R; Mayer, A

    1999-01-01

    Several resonances of the capture reaction sup 2 sup 0 Ne(alpha, gamma) sup 2 sup 4 Mg were measured using an extended windowless gas target system. Detailed GEANT simulations were performed to derive the strength and the total width of the resonances from the measured yield curve. The crucial experimental parameters, which are mainly the density profile in the gas target and the efficiency of the gamma-ray detector, were analyzed by a comparison between the measured data and the corresponding simulation calculations. The excellent agreement between the experimental data and the simulations gives detailed insight into these parameters. (author)

  19. Hydrodynamic efficiency and thermal transport in planar target experiments at LLE

    International Nuclear Information System (INIS)

    Boehly, T.; Goldman, L.M.; Seka, W.; Craxton, R.S.

    1984-01-01

    The authors report the results of single beam irradiation of thin CH foils at laser intensities of 10 13 to 10 15 W/cm 2 in 0.8 ns pulses containing 20 to 50 J of 350 nm and 1054 nm light. They also discuss the hydrodynamic efficiency, thermal transport and preheat in these targets. Included is the measurement of the ion blowoff energy distribution and velocity. The efficient acceleration by short wavelength radiation causes target displacements comparable to the spot size resulting in two-dimension effects. The results are adequately modeled with the 2-D hydrocode SAGE using a flux limiter of f=0.04

  20. Proteomic cornerstones of hematopoietic stem cell differentiation

    DEFF Research Database (Denmark)

    Klimmeck, Daniel; Hansson, Jenny; Raffel, Simon

    2012-01-01

    Regenerative tissues such as the skin epidermis, the intestinal mucosa or the hematopoietic system are organized in a hierarchical manner with stem cells building the top of this hierarchy. Somatic stem cells harbor the highest self-renewal activity and generate a series of multipotent progenitors...... which differentiate into lineage committed progenitors and subsequently mature cells. In this report, we applied an in-depth quantitative proteomic approach to analyze and compare the full proteomes of ex vivo isolated and FACS-sorted populations highly enriched for either multipotent hematopoietic stem....../progenitor cells (HSPCs, Lin(neg)Sca-1(+)c-Kit(+)) or myeloid committed precursors (Lin(neg)Sca-1(-)c-Kit(+)). By employing stable isotope dimethyl labeling and high-resolution mass spectrometry, more than 5,000 proteins were quantified. From biological triplicate experiments subjected to rigorous statistical...

  1. Probing the Proteome on Earth and Beyond

    Science.gov (United States)

    Ostrom, P.

    2008-12-01

    Less than a decade ago, protein sequencing was the bane of paleobiology. Since that time researchers have completely sequenced proteins in >50 Ka fossils, been dazzled by reports of collagen peptides in dinosaur bones, and witnessed the development of phylogenetic trees from ancient protein sequences. Enlisting proteomics as biosignature is now in our grasp. In this talk the pitfalls and challenges of mass spectrometric approaches to protein sequencing will be illustrated and phylogenetic applications will be discussed. Work on extinct organisms at Michigan State University, University of Michigan and York University will provide a vantage point to assess methodologies, explore diagenetic alterations, evaluate mass spectra and illustrate issues associated with data base searching. Challenges encountered in the study of paleoproteomics, such as the absence of sequences for extinct organisms in commercially available databases, protein diagenesis and low concentrations of target are parallel to those that will be encountered when protein sequencing is extended to extreme and extraterrestrial environments. Thus, lessons learned from interrogating the ancient proteome are important and necessary step in developing proteomics as a biosignature tools.

  2. Experimental study of ablation pressures and target velocities obtained in 0. 26. mu. m wavelength laser experiments in planar geometry

    Energy Technology Data Exchange (ETDEWEB)

    Fabbro, R.; Faral, B.; Virmont, J.; Cottet, F.; Romain, J.P.; Pepin, H.

    1985-11-01

    In 0.26 ..mu..m wavelength laser experiments that were performed in planar geometry with irradiances between 10/sup 13/ and 10/sup 15/ W/cm/sup 2/, the ablation pressure and the target velocity have been measured using a shock-velocity measurement and the double foil technique, respectively. The conditions are discussed that must be satisfied if the double-foil technique is to give an accurate measurement of the velocity of the dense part of the target. The rocket model has also been improved using a time-dependent applied pressure pulse, in order to accurately describe the relation between ablation pressure, target velocity, and ablated fraction. Pressures up to 50 Mbar have been easily generated since lateral energy transport is rather low with a 0.26 ..mu..m wavelength laser.

  3. Nike Experiment to Observe Strong Areal Mass Oscillations in a Rippled Target Hit by a Short Laser Pulse

    Science.gov (United States)

    Aglitskiy, Y.; Karasik, M.; Velikovich, A. L.; Serlin, V.; Weaver, J. L.; Kessler, T. J.; Schmitt, A. J.; Obenschain, S. P.; Metzler, N.; Oh, J.

    2010-11-01

    When a short (sub-ns) laser pulse deposits finite energy in a target, the shock wave launched into it is immediately followed by a rarefaction wave. If the irradiated surface is rippled, theory and simulations predict strong oscillations of the areal mass perturbation amplitude in the target [A. L. Velikovich et al., Phys. Plasmas 10, 3270 (2003).] The first experiment designed to observe this effect has become possible by adding short-driving-pulse capability to the Nike laser, and has been scheduled for the fall of 2010. Simulations show that while the driving pulse of 0.3 ns is on, the areal mass perturbation amplitude grows by a factor ˜2 due to ablative Richtmyer-Meshkov instability. It then decreases, reverses phase, and reaches another maximum, also about twice its initial value, shortly after the shock breakout at the rear target surface. This signature behavior is observable with the monochromatic x-ray imaging diagnostics fielded on Nike.

  4. Small Molecule Sequential Dual-Targeting Theragnostic Strategy (SMSDTTS): from Preclinical Experiments towards Possible Clinical Anticancer Applications.

    Science.gov (United States)

    Li, Junjie; Oyen, Raymond; Verbruggen, Alfons; Ni, Yicheng

    2013-01-01

    Hitting the evasive tumor cells proves challenging in targeted cancer therapies. A general and unconventional anticancer approach namely small molecule sequential dual-targeting theragnostic strategy (SMSDTTS) has recently been introduced with the aims to target and debulk the tumor mass, wipe out the residual tumor cells, and meanwhile enable cancer detectability. This dual targeting approach works in two steps for systemic delivery of two naturally derived drugs. First, an anti-tubulin vascular disrupting agent, e.g., combretastatin A4 phosphate (CA4P), is injected to selectively cut off tumor blood supply and to cause massive necrosis, which nevertheless always leaves peripheral tumor residues. Secondly, a necrosis-avid radiopharmaceutical, namely (131)I-hypericin ((131)I-Hyp), is administered the next day, which accumulates in intratumoral necrosis and irradiates the residual cancer cells with beta particles. Theoretically, this complementary targeted approach may biologically and radioactively ablate solid tumors and reduce the risk of local recurrence, remote metastases, and thus cancer mortality. Meanwhile, the emitted gamma rays facilitate radio-scintigraphy to detect tumors and follow up the therapy, hence a simultaneous theragnostic approach. SMSDTTS has now shown promise from multicenter animal experiments and may demonstrate unique anticancer efficacy in upcoming preliminary clinical trials. In this short review article, information about the two involved agents, the rationale of SMSDTTS, its preclinical antitumor efficacy, multifocal targetability, simultaneous theragnostic property, and toxicities of the dose regimens are summarized. Meanwhile, possible drawbacks, practical challenges and future improvement with SMSDTTS are discussed, which hopefully may help to push forward this strategy from preclinical experiments towards possible clinical applications.

  5. Serum proteome profiling in canine idiopathic dilated cardiomyopathy using TMT-based quantitative proteomics approach.

    Science.gov (United States)

    Bilić, Petra; Guillemin, Nicolas; Kovačević, Alan; Beer Ljubić, Blanka; Jović, Ines; Galan, Asier; Eckersall, Peter David; Burchmore, Richard; Mrljak, Vladimir

    2018-05-15

    Idiopathic dilated cardiomyopathy (iDCM) is a primary myocardial disorder with an unknown aetiology, characterized by reduced contractility and ventricular dilation of the left or both ventricles. Naturally occurring canine iDCM was used herein to identify serum proteomic signature of the disease compared to the healthy state, providing an insight into underlying mechanisms and revealing proteins with biomarker potential. To achieve this, we used high-throughput label-based quantitative LC-MS/MS proteomics approach and bioinformatics analysis of the in silico inferred interactome protein network created from the initial list of differential proteins. To complement the proteomic analysis, serum biochemical parameters and levels of know biomarkers of cardiac function were measured. Several proteins with biomarker potential were identified, such as inter-alpha-trypsin inhibitor heavy chain H4, microfibril-associated glycoprotein 4 and apolipoprotein A-IV, which were validated using an independent method (Western blotting) and showed high specificity and sensitivity according to the receiver operating characteristic curve analysis. Bioinformatics analysis revealed involvement of different pathways in iDCM, such as complement cascade activation, lipoprotein particles dynamics, elastic fibre formation, GPCR signalling and respiratory electron transport chain. Idiopathic dilated cardiomyopathy is a severe primary myocardial disease of unknown cause, affecting both humans and dogs. This study is a contribution to the canine heart disease research by means of proteomic and bioinformatic state of the art analyses, following similar approach in human iDCM research. Importantly, we used serum as non-invasive and easily accessible biological source of information and contributed to the scarce data on biofluid proteome research on this topic. Bioinformatics analysis revealed biological pathways modulated in canine iDCM with potential of further targeted research. Also, several

  6. Farm animal proteomics - A review

    DEFF Research Database (Denmark)

    Bendixen, Emøke; Danielsen, Marianne; Hollung, Kristin

    2011-01-01

    In agricultural sciences as in all other areas of life science, the implementation of proteomics and other post-genomic tools is an important step towards more detailed understanding of the complex biological systems that control physiology and pathology of living beings. Farm animals are raised...... and cattle are relevant not only for farm animal sciences, but also for adding to our understanding of complex biological mechanisms of health and disease in humans. The aim of this review is to present an overview of the specific topics of interest within farm animal proteomics, and to highlight some...... of the areas where synergy between classic model organism proteomics and farm animal proteomics is rapidly emerging. Focus will be on introducing the special biological traits that play an important role in food production, and on how proteomics may help optimize farm animal production...

  7. Integrated laser-target interaction experiments on the RAL petawatt laser

    International Nuclear Information System (INIS)

    Patel, P K; Key, M H; Mackinnon, A J

    2005-01-01

    We review a recent experimental campaign to study the interaction physics of petawatt laser pulses incident at relativistic intensities on solid targets. The campaign was performed on the 500 J sub-picosecond petawatt laser at the Rutherford Appleton Laboratory. An extensive suite of optical, x-ray, and particle diagnostics was employed to characterise the processes of laser absorption, electron generation and transport, thermal and K-alpha x-ray generation, and proton acceleration

  8. Active target with plastic scintillating fibers for hyperon-proton scattering experiments

    Czech Academy of Sciences Publication Activity Database

    Ahn, J. K.; Akikawa, H.; Arvieux, H.; Bassalleck, B.; Chung, M. S.; En'yo, H.; Fukuda, T.; Funahashi, H.; Golovkin, SV.; Gorin, AM.; Goto, Y.; Hanabata, M.; Hayakawa, T.; Ichikawa, A.; Ieiri, M.; Imai, K.; Ishino, M.; Kanda, H.; Kim, Y. D.; Kondo, Y.; Kozarenko, E. N.; Kreslo, I. E.; Lee, J. M.; Masaike, A.; Mihara, S.; Nakai, K.; Nakazawa, K.; Ozawa, K.; Sato, A.; Sato, H. D.; Sim, K. S.; Tabaru, T.; Takeutchi, F.; Tlustý, Pavel; Torii, H.; Yamamoto, K.; Yokkaichi, S.; Yoshida, M.

    2002-01-01

    Roč. 49, č. 2 (2002), s. 592-596 ISSN 0018-9499 R&D Projects: GA AV ČR IAA1048304; GA AV ČR KSK1048102 Institutional research plan: CEZ:AV0Z1048901 Keywords : active target * hyperon-proton scattering * scintillating fibers Subject RIV: BG - Nuclear, Atomic and Molecular Physics, Colliders Impact factor: 1.431, year: 2002

  9. A simplified regimen of targeted antifungal prophylaxis in liver transplant recipients: A single-center experience.

    Science.gov (United States)

    Lavezzo, B; Patrono, D; Tandoi, F; Martini, S; Fop, F; Ballerini, V; Stratta, C; Skurzak, S; Lupo, F; Strignano, P; Donadio, P P; Salizzoni, M; Romagnoli, R; De Rosa, F G

    2018-04-01

    Invasive fungal infection (IFI) is a severe complication of liver transplantation burdened by high mortality. Guidelines recommend targeted rather than universal antifungal prophylaxis based on tiers of risk. We aimed to evaluate IFI incidence, risk factors, and outcome after implementation of a simplified two-tiered targeted prophylaxis regimen based on a single broad-spectrum antifungal drug (amphotericin B). Patients presenting 1 or more risk factors according to literature were administered prophylaxis. Prospectively collected data on all adult patients transplanted in Turin from January 2011 to December 2015 were reviewed. Patients re-transplanted before postoperative day 7 were considered once, yielding a study cohort of 581 cases. Prophylaxis was administered to 299 (51.4%) patients; adherence to protocol was 94.1%. Sixteen patients developed 18 IFIs for an overall rate of 2.8%. All IFI cases were in targeted prophylaxis group; none of the non-prophylaxis group developed IFI. Most cases (81.3%) presented within 30 days after transplantation during prophylaxis; predominant pathogens were molds (94.4%). Only 1 case of candidemia was observed. One-year mortality in IFI patients was 33.3% vs 6.4% in patients without IFI (P = .001); IFI attributable mortality was 6.3%. At multivariate analysis, significant risk factors for IFI were renal replacement therapy (OR = 8.1) and re-operation (OR = 5.2). The implementation of a simplified targeted prophylaxis regimen appeared to be safe and applicable and was associated with low IFI incidence and mortality. Association of IFI with re-operation and renal replacement therapy calls for further studies to identify optimal prophylaxis in this subset of patients. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  10. A 3 ps synchronised multi-frame photographic diagnostic for target experiments with the iodine laser

    International Nuclear Information System (INIS)

    Maaswinkel, A.G.M.; Sigel, R.; Baumhacker, H.; Brederlow, G.

    1982-10-01

    A laser system is described with which we obtain a sequence of 6 pictures (interferograms or shadowgrams) of the plasma produced by the iodine laser on solid targets. The system consists of a synchronously pumped dye laser amplified in dye cells pumped by an excimer laser. It delivers a pulse with an energy of 400 μJ and a length of 3 ps at a wavelength of 580 nm that is highly synchronous with the iodine pulse. (orig.)

  11. Being targeted: Young women's experience of being identified for a teenage pregnancy prevention programme.

    Science.gov (United States)

    Sorhaindo, Annik; Bonell, Chris; Fletcher, Adam; Jessiman, Patricia; Keogh, Peter; Mitchell, Kirstin

    2016-06-01

    Research on the unintended consequences of targeting 'high-risk' young people for health interventions is limited. Using qualitative data from an evaluation of the Teens & Toddlers Pregnancy Prevention programme, we explored how young women experienced being identified as at risk for teenage pregnancy to understand the processes via which unintended consequences may occur. Schools' lack of transparency regarding the targeting strategy and criteria led to feelings of confusion and mistrust among some young women. Black and minority ethnic young women perceived that the assessment of their risk was based on stereotyping. Others felt their outgoing character was misinterpreted as signifying risk. To manage these imposed labels, stigma and reputational risks, young women responded to being targeted by adopting strategies, such as distancing, silence and refusal. To limit harmful consequences, programmes could involve prospective participants in determining their need for intervention or introduce programmes for young people at all levels of risk. Copyright © 2016 The Foundation for Professionals in Services for Adolescents. Published by Elsevier Ltd. All rights reserved.

  12. Proteomics research in India: an update.

    Science.gov (United States)

    Reddy, Panga Jaipal; Atak, Apurva; Ghantasala, Saicharan; Kumar, Saurabh; Gupta, Shabarni; Prasad, T S Keshava; Zingde, Surekha M; Srivastava, Sanjeeva

    2015-09-08

    After a successful completion of the Human Genome Project, deciphering the mystery surrounding the human proteome posed a major challenge. Despite not being largely involved in the Human Genome Project, the Indian scientific community contributed towards proteomic research along with the global community. Currently, more than 76 research/academic institutes and nearly 145 research labs are involved in core proteomic research across India. The Indian researchers have been major contributors in drafting the "human proteome map" along with international efforts. In addition to this, virtual proteomics labs, proteomics courses and remote triggered proteomics labs have helped to overcome the limitations of proteomics education posed due to expensive lab infrastructure. The establishment of Proteomics Society, India (PSI) has created a platform for the Indian proteomic researchers to share ideas, research collaborations and conduct annual conferences and workshops. Indian proteomic research is really moving forward with the global proteomics community in a quest to solve the mysteries of proteomics. A draft map of the human proteome enhances the enthusiasm among intellectuals to promote proteomic research in India to the world.This article is part of a Special Issue entitled: Proteomics in India. Copyright © 2015 Elsevier B.V. All rights reserved.

  13. Tyrosine-Nitrated Proteins: Proteomic and Bioanalytical Aspects.

    Science.gov (United States)

    Batthyány, Carlos; Bartesaghi, Silvina; Mastrogiovanni, Mauricio; Lima, Analía; Demicheli, Verónica; Radi, Rafael

    2017-03-01

    "Nitroproteomic" is under active development, as 3-nitrotyrosine in proteins constitutes a footprint left by the reactions of nitric oxide-derived oxidants that are usually associated to oxidative stress conditions. Moreover, protein tyrosine nitration can cause structural and functional changes, which may be of pathophysiological relevance for human disease conditions. Biological protein tyrosine nitration is a free radical process involving the intermediacy of tyrosyl radicals; in spite of being a nonenzymatic process, nitration is selectively directed toward a limited subset of tyrosine residues. Precise identification and quantitation of 3-nitrotyrosine in proteins has represented a "tour de force" for researchers. Recent Advances: A small number of proteins are preferential targets of nitration (usually less than 100 proteins per proteome), contrasting with the large number of proteins modified by other post-translational modifications such as phosphorylation, acetylation, and, notably, S-nitrosation. Proteomic approaches have revealed key features of tyrosine nitration both in vivo and in vitro, including selectivity, site specificity, and effects in protein structure and function. Identification of 3-nitrotyrosine-containing proteins and mapping nitrated residues is challenging, due to low abundance of this oxidative modification in biological samples and its unfriendly behavior in mass spectrometry (MS)-based technologies, that is, MALDI, electrospray ionization, and collision-induced dissociation. The use of (i) classical two-dimensional electrophoresis with immunochemical detection of nitrated proteins followed by protein ID by regular MS/MS in combination with (ii) immuno-enrichment of tyrosine-nitrated peptides and (iii) identification of nitrated peptides by a MIDAS™ experiment is arising as a potent methodology to unambiguously map and quantitate tyrosine-nitrated proteins in vivo. Antioxid. Redox Signal. 26, 313-328.

  14. The gel electrophoresis markup language (GelML) from the Proteomics Standards Initiative.

    Science.gov (United States)

    Gibson, Frank; Hoogland, Christine; Martinez-Bartolomé, Salvador; Medina-Aunon, J Alberto; Albar, Juan Pablo; Babnigg, Gyorgy; Wipat, Anil; Hermjakob, Henning; Almeida, Jonas S; Stanislaus, Romesh; Paton, Norman W; Jones, Andrew R

    2010-09-01

    The Human Proteome Organisation's Proteomics Standards Initiative has developed the GelML (gel electrophoresis markup language) data exchange format for representing gel electrophoresis experiments performed in proteomics investigations. The format closely follows the reporting guidelines for gel electrophoresis, which are part of the Minimum Information About a Proteomics Experiment (MIAPE) set of modules. GelML supports the capture of metadata (such as experimental protocols) and data (such as gel images) resulting from gel electrophoresis so that laboratories can be compliant with the MIAPE Gel Electrophoresis guidelines, while allowing such data sets to be exchanged or downloaded from public repositories. The format is sufficiently flexible to capture data from a broad range of experimental processes, and complements other PSI formats for MS data and the results of protein and peptide identifications to capture entire gel-based proteome workflows. GelML has resulted from the open standardisation process of PSI consisting of both public consultation and anonymous review of the specifications.

  15. C-STrap Sample Preparation Method--In-Situ Cysteinyl Peptide Capture for Bottom-Up Proteomics Analysis in the STrap Format.

    Science.gov (United States)

    Zougman, Alexandre; Banks, Rosamonde E

    2015-01-01

    Recently we introduced the concept of Suspension Trapping (STrap) for bottom-up proteomics sample processing that is based upon SDS-mediated protein extraction, swift detergent removal and rapid reactor-type protein digestion in a quartz depth filter trap. As the depth filter surface is made of silica, it is readily modifiable with various functional groups using the silane coupling chemistries. Thus, during the digest, peptides possessing specific features could be targeted for enrichment by the functionalized depth filter material while non-targeted peptides could be collected as an unbound distinct fraction after the digest. In the example presented here the quartz depth filter surface is functionalized with the pyridyldithiol group therefore enabling reversible in-situ capture of the cysteine-containing peptides generated during the STrap-based digest. The described C-STrap method retains all advantages of the original STrap methodology and provides robust foundation for the conception of the targeted in-situ peptide fractionation in the STrap format for bottom-up proteomics. The presented data support the method's use in qualitative and semi-quantitative proteomics experiments.

  16. C-STrap Sample Preparation Method--In-Situ Cysteinyl Peptide Capture for Bottom-Up Proteomics Analysis in the STrap Format.

    Directory of Open Access Journals (Sweden)

    Alexandre Zougman

    Full Text Available Recently we introduced the concept of Suspension Trapping (STrap for bottom-up proteomics sample processing that is based upon SDS-mediated protein extraction, swift detergent removal and rapid reactor-type protein digestion in a quartz depth filter trap. As the depth filter surface is made of silica, it is readily modifiable with various functional groups using the silane coupling chemistries. Thus, during the digest, peptides possessing specific features could be targeted for enrichment by the functionalized depth filter material while non-targeted peptides could be collected as an unbound distinct fraction after the digest. In the example presented here the quartz depth filter surface is functionalized with the pyridyldithiol group therefore enabling reversible in-situ capture of the cysteine-containing peptides generated during the STrap-based digest. The described C-STrap method retains all advantages of the original STrap methodology and provides robust foundation for the conception of the targeted in-situ peptide fractionation in the STrap format for bottom-up proteomics. The presented data support the method's use in qualitative and semi-quantitative proteomics experiments.

  17. Target development and transmutation experiments in the frame of the EFTTRA European collaboration

    International Nuclear Information System (INIS)

    Prunier, C.; Salvatores, M.; Muehling, G.; Rome, M.

    1995-01-01

    The aim of the EFTTRA collaboration between CEA (France), ECN (The Netherlands), EDF (France), FZK (Germany), IAM and ITU (European Commission), is to organize joint experiments for the study of materials for transmutation in reactors. The work is focused on the transmutation of 99 Tc (metal), of 129 I (compound), and of Am (in an inert matrix). Irradiation experiments are taking place in parallel in the Phenix fast reactor in France, and in the high flux thermal reactor HFR in the Netherlands. Examination of iodine compounds and Tc samples, following irradiation in HFR, has started. (authors). 10 refs., 2 figs

  18. A free Hg jet system for use in a high-power target experiment

    CERN Document Server

    Spampinato, Philip; Gabriel, Tony A; Graves, Van; Haseroth, H; Kirk, Harold G; Lettry, Jacques; McDonald, Kirk T; Rennich, Mark; Simos, Nikolaos; Titus, P; Tsang, Thomas

    2005-01-01

    We describe a mercury jet system that is suitable for insertion into the 15cm diameter bore of a high-field solenoid magnet. The device features a hermetically sealed primary containment volume which is enclosed in a secondary containment system to insure isolation of mercury vapors from the remaining experimental environment. The jet diameter is 1-cm while the jet velocity will be up to 20 m/s. Optical diagnostics is incorporated into the target design to allow observation of the dispersal of the mercury as a result of interaction with a 24 GeV proton beam with up to 20 x 10

  19. Readout electronics validation and target detector assessment for the Neutrinos Angra experiment

    International Nuclear Information System (INIS)

    Alvarenga, T.A.; Anjos, J.C.; Azzi, G.; Cerqueira, A.S.; Chimenti, P.; Costa, J.A.; Dornelas, T.I.; Farias, P.C.M.A.; Guedes, G.P.; Gonzalez, L.F.G.; Kemp, E.; Lima, H.P.; Machado, R.; Nóbrega, R.A.; Pepe, I.M.; Ribeiro, D.B.S.; Simas Filho, E.F.; Valdiviesso, G.A.; Wagner, S.

    2016-01-01

    A compact surface detector designed to identify the inverse beta decay interaction produced by anti-neutrinos coming from near operating nuclear reactors is being developed by the Neutrinos Angra Collaboration. In this document we describe and test the detector and its readout system by means of cosmic rays acquisition. In this measurement campaign, the target detector has been equipped with 16 8-in PMTs and two scintillator paddles have been used to trigger cosmic ray events. The achieved results disclosed the main operational characteristics of the Neutrinos Angra system and have been used to assess the detector and to validate its readout system.

  20. One of the polarized targets that was developed for the S134 experiment

    CERN Multimedia

    1974-01-01

    The target is polarized dynamically as usual in a 25 kg homogeneous magnetic field. It is then cooled to some 50 millidegrees and moved into the large gap of the ETH spectrometer magnet, where the field is 10 kg, with a poorer homogeneity. It stands in front of the beam, in the centre of the detection system, for studying all the spin parameters in the reaction pi-p - K0LAMBDA0 at 5 GeV/c, with an available solid angle of nearly 4 p.

  1. Exploring the human plasma proteome for humoral mediators of remote ischemic preconditioning--a word of caution.

    Directory of Open Access Journals (Sweden)

    Erik Helgeland

    Full Text Available Despite major advances in early revascularization techniques, cardiovascular diseases are still the leading cause of death worldwide, and myocardial infarctions contribute heavily to this. Over the past decades, it has become apparent that reperfusion of blood to a previously ischemic area of the heart causes damage in and of itself, and that this ischemia reperfusion induced injury can be reduced by up to 50% by mechanical manipulation of the blood flow to the heart. The recent discovery of remote ischemic preconditioning (RIPC provides a non-invasive approach of inducing this cardioprotection at a distance. Finding its endogenous mediators and their operative mode is an important step toward increasing the ischemic tolerance. The release of humoral factor(s upon RIPC was recently demonstrated and several candidate proteins were published as possible mediators of the cardioprotection. Before clinical applicability, these potential biomarkers and their efficiency must be validated, a task made challenging by the large heterogeneity in reported data and results. Here, in an attempt to reproduce and provide more experimental data on these mediators, we conducted an unbiased in-depth analysis of the human plasma proteome before and after RIPC. From the 68 protein markers reported in the literature, only 28 could be mapped to manually reviewed (Swiss-Prot protein sequences. 23 of them were monitored in our untargeted experiment. However, their significant regulation could not be reproducibly estimated. In fact, among the 394 plasma proteins we accurately quantified, no significant regulation could be confidently and reproducibly assessed. This indicates that it is difficult to both monitor and reproduce published data from experiments exploring for RIPC induced plasma proteomic regulations, and suggests that further work should be directed towards small humoral factors. To simplify this task, we made our proteomic dataset available via Proteome

  2. Turbulent heat mixing of a heavy liquid metal flow in the MEGAPIE target geometry-The heated jet experiment

    International Nuclear Information System (INIS)

    Stieglitz, Robert; Daubner, Markus; Batta, A.; Lefhalm, C.-H.

    2007-01-01

    The MEGAPIE target installed at the Paul-Scherrer Institute is an example of a spallation target using eutectic liquid lead-bismuth (Pb 45 Bi 55 ) both as coolant and neutron source. An adequate cooling of the target requires a conditioning of the flow, which is realized by a main flow transported in an annular gap downwards, u-turned at a hemispherical shell into a cylindrical riser tube. In order to avoid a stagnation point close to the lowest part of the shell a jet flow is superimposed to the main flow, which is directed towards to the stagnation point and flows tangentially along the shell. The heated jet experiment conducted in the THEADES loop of the KALLA laboratory is nearly 1:1 representation of the lower part of the MEGAPIE target. It is aimed to study the cooling capability of this specific geometry in dependence on the flow rate ratio (Q main /Q jet ) of the main flow (Q main ) to the jet flow (Q jet ). Here, a heated jet is injected into a cold main flow at MEGAPIE relevant flow rate ratios. The liquid metal experiment is accompanied by a water experiment in almost the same geometry to study the momentum field as well as a three-dimensional turbulent numerical fluid dynamic simulation (CFD). Besides a detailed study of the envisaged nominal operation of the MEGAPIE target with Q main /Q jet = 15 deviations from this mode are investigated in the range from 7.5 ≤ Q main /Q jet ≤ 20 in order to give an estimate on the safe operational threshold of the target. The experiment shows that, the flow pattern establishing in this specific design and the turbulence intensity distribution essentially depends on the flow rate ratio (Q main /Q jet ). All Q main /Q jet -ratios investigated exhibit an unstable time dependent behavior. The MEGAPIE design is highly sensitive against changes of this ratio. Mainly three completely different flow patterns were identified. A sufficient cooling of the lower target shell, however, is only ensured if Q main /Q jet ≤ 12

  3. Monitoring the World Health Organization Global Target 2025 for Exclusive Breastfeeding: Experience From the United States.

    Science.gov (United States)

    Gupta, Priya M; Perrine, Cria G; Chen, Jian; Elam-Evans, Laurie D; Flores-Ayala, Rafael

    2017-08-01

    Exclusive breastfeeding under 6 months, calculated from a single 24-hour recall among mothers of children 0 to 5 months of age, is a World Health Organization (WHO) indicator used to monitor progress on the 2025 global breastfeeding target. Many upper-middle-income and high-income countries, including the United States, do not have estimates for this indicator. Research aim: To describe the prevalence of exclusive breastfeeding under 6 months in the United States. We used a single 24-hour dietary recall from the National Health and Nutrition Examination Survey 2009-2012 to calculate the prevalence of exclusive breastfeeding under 6 months. We discuss our results in the context of routine breastfeeding surveillance, which is reported from a national survey with different methodology. Among children younger than 6 months, 24.4%, 95% confidence interval [17.6, 31.1], were exclusively breastfed the previous day. To our knowledge, this is the first estimate of the WHO indicator of exclusive breastfeeding under 6 months for the United States. This study supports the global surveillance and data strategy for reporting to the WHO on the 2025 target for exclusive breastfeeding.

  4. Korea's nuclear public information experiences-target groups and communication strategies

    International Nuclear Information System (INIS)

    Chung, J.K.

    1996-01-01

    Why public information activities in Korea are needed is first explained. There are three basic reasons; 1) to secure necessary sites for construction of large nuclear facilities; such as nuclear power plants, radwaste management facilities, and nuclear fuel-cycle related facilities 2) to maintain a friendly relationship between the local communities and the nuclear industries, 3) to promote better understanding about the nation's peaceful nuclear programs to the various target groups. Categorization of target groups and messages are reviewed. By whom the public information programs are implemented is also explained. An orchestrated effort together with the third communicators is stressed. Basic philosophy of nuclear public information programs is introduced. A high-profile information campaign and a low-profile information campaign are explained. Particular information strategies suitable to Korean situation as examined. In addition, the Korean general public perception on nuclear energy is briefly introduced. Also, some real insights of anti-nuclear movement in Korea together with the arguments are reviewed. In conclusion, the paper stresses that nuclear arguments became no more technical matters but almost socio-political issues. (author)

  5. Detection of ROS Induced Proteomic Signatures by Mass Spectrometry

    Directory of Open Access Journals (Sweden)

    Brian McDonagh

    2017-07-01

    Full Text Available Reversible and irreversible post-translational modifications (PTMs induced by endogenously generated reactive oxygen species (ROS in regulatory enzymes and proteins plays an essential role in cellular signaling. Almost all cellular processes including metabolism, transcription, translation and degradation have been identified as containing redox regulated proteins. Specific redox modifications of key amino acids generated by ROS offers a dynamic and versatile means to rapidly alter the activity or functional structure of proteins in response to biochemical, environmental, genetic and pathological perturbations. How the proteome responds to these stimuli is of critical importance in oxidant physiology, as it can regulate the cell stress response by reversible and irreversible PTMs, affecting protein activity and protein-protein interactions. Due to the highly labile nature of many ROS species, applying redox proteomics can provide a signature footprint of the ROS species generated. Ideally redox proteomic approaches would allow; (1 the identification of the specific PTM, (2 identification of the amino acid residue that is modified and (3 the percentage of the protein containing the PTM. New developments in MS offer the opportunity of a more sensitive targeted proteomic approach and retrospective data analysis. Subsequent bioinformatics analysis can provide an insight into the biochemical and physiological pathways or cell signaling cascades that are affected by ROS generation. This mini-review will detail current redox proteomic approaches to identify and quantify ROS induced PTMs and the subsequent effects on cellular signaling.

  6. Recent advances and opportunities in proteomic analyses of tumour heterogeneity.

    Science.gov (United States)

    Bateman, Nicholas W; Conrads, Thomas P

    2018-04-01

    Solid tumour malignancies comprise a highly variable admixture of tumour and non-tumour cellular populations, forming a complex cellular ecosystem and tumour microenvironment. This tumour heterogeneity is not incidental, and is known to correlate with poor patient prognosis for many cancer types. Indeed, non-malignant cell populations, such as vascular endothelial and immune cells, are known to play key roles supporting and, in some cases, driving aggressive tumour biology, and represent targets of emerging therapeutics, such as antiangiogenesis and immune checkpoint inhibitors. The biochemical interplay between these cellular populations and how they contribute to molecular tumour heterogeneity remains enigmatic, particularly from the perspective of the tumour proteome. This review focuses on recent advances in proteomic methods, namely imaging mass spectrometry, single-cell proteomic techniques, and preanalytical sample processing, that are uniquely positioned to enable detailed analysis of discrete cellular populations within tumours to improve our understanding of tumour proteomic heterogeneity. This review further emphasizes the opportunity afforded by the application of these techniques to the analysis of tumour heterogeneity in formalin-fixed paraffin-embedded archival tumour tissues, as these represent an invaluable resource for retrospective analyses that is now routinely accessible, owing to recent technological and methodological advances in tumour tissue proteomics. Copyright © 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. Copyright © 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

  7. Magnetoresistive biosensors for quantitative proteomics

    Science.gov (United States)

    Zhou, Xiahan; Huang, Chih-Cheng; Hall, Drew A.

    2017-08-01

    Quantitative proteomics, as a developing method for study of proteins and identification of diseases, reveals more comprehensive and accurate information of an organism than traditional genomics. A variety of platforms, such as mass spectrometry, optical sensors, electrochemical sensors, magnetic sensors, etc., have been developed for detecting proteins quantitatively. The sandwich immunoassay is widely used as a labeled detection method due to its high specificity and flexibility allowing multiple different types of labels. While optical sensors use enzyme and fluorophore labels to detect proteins with high sensitivity, they often suffer from high background signal and challenges in miniaturization. Magnetic biosensors, including nuclear magnetic resonance sensors, oscillator-based sensors, Hall-effect sensors, and magnetoresistive sensors, use the specific binding events between magnetic nanoparticles (MNPs) and target proteins to measure the analyte concentration. Compared with other biosensing techniques, magnetic sensors take advantage of the intrinsic lack of magnetic signatures in biological samples to achieve high sensitivity and high specificity, and are compatible with semiconductor-based fabrication process to have low-cost and small-size for point-of-care (POC) applications. Although still in the development stage, magnetic biosensing is a promising technique for in-home testing and portable disease monitoring.

  8. Semi-inclusive DIS Experiments Using Transversely Polarized Targets in Hall-A: Current Results and Future Plans

    Directory of Open Access Journals (Sweden)

    Allada Kalyan

    2012-12-01

    Full Text Available Measurement of single (SSA and double spin asymmetries (DSA in semiinclusive DIS reactions using polarized targets provide a powerful method to probe transverse momentum dependent parton distribution functions (TMDs. In particular, the experimentally measured SSA on nucleon targets can help in extracting the transversity and Sivers distribution functions of u and d-quarks. Similarly, the measured DSA are sensitive to the quark spin-orbital correlations, and provide an access to the TMD parton distribution function (g1T. A recent experiment conducted in Hall-A Jefferson Lab using transversely polarized 3He provide first such measurements on “effective” neutron target. The measurement was performed using 5.9 GeV beam from CEBAF and measured the target SSA/DSA in the SIDIS reaction 3He↑(e, e′π±X. The kinematical range, x = 0.19 ~ 0.34, at Q2 = 1.77 ~ 2.73 (GeV/c2, was focused on the valence quark region. The results from this measurement along with our plans for future high precision measurements in Hall-A are presented.

  9. Proteomics of Maize Root Development.

    Science.gov (United States)

    Hochholdinger, Frank; Marcon, Caroline; Baldauf, Jutta A; Yu, Peng; Frey, Felix P

    2018-01-01

    Maize forms a complex root system with structurally and functionally diverse root types that are formed at different developmental stages to extract water and mineral nutrients from soil. In recent years proteomics has been intensively applied to identify proteins involved in shaping the three-dimensional architecture and regulating the function of the maize root system. With the help of developmental mutants, proteomic changes during the initiation and emergence of shoot-borne, lateral and seminal roots have been examined. Furthermore, root hairs were surveyed to understand the proteomic changes during the elongation of these single cell type structures. In addition, primary roots have been used to study developmental changes of the proteome but also to investigate the proteomes of distinct tissues such as the meristematic zone, the elongation zone as well as stele and cortex of the differentiation zone. Moreover, subcellular fractions of the primary root including cell walls, plasma membranes and secreted mucilage have been analyzed. Finally, the superior vigor of hybrid seedling roots compared to their parental inbred lines was studied on the proteome level. In summary, these studies provide novel insights into the complex proteomic interactions of the elaborate maize root system during development.

  10. Proteomics of Maize Root Development

    Directory of Open Access Journals (Sweden)

    Frank Hochholdinger

    2018-03-01

    Full Text Available Maize forms a complex root system with structurally and functionally diverse root types that are formed at different developmental stages to extract water and mineral nutrients from soil. In recent years proteomics has been intensively applied to identify proteins involved in shaping the three-dimensional architecture and regulating the function of the maize root system. With the help of developmental mutants, proteomic changes during the initiation and emergence of shoot-borne, lateral and seminal roots have been examined. Furthermore, root hairs were surveyed to understand the proteomic changes during the elongation of these single cell type structures. In addition, primary roots have been used to study developmental changes of the proteome but also to investigate the proteomes of distinct tissues such as the meristematic zone, the elongation zone as well as stele and cortex of the differentiation zone. Moreover, subcellular fractions of the primary root including cell walls, plasma membranes and secreted mucilage have been analyzed. Finally, the superior vigor of hybrid seedling roots compared to their parental inbred lines was studied on the proteome level. In summary, these studies provide novel insights into the complex proteomic interactions of the elaborate maize root system during development.

  11. Proteomic Signatures of Thymomas.

    Directory of Open Access Journals (Sweden)

    Linan Wang

    Full Text Available Based on the histological features and outcome, the current WHO classification separates thymomas into A, AB, B1, B2 and B3 subtypes. It is hypothesized that the type A thymomas are derived from the thymic medulla while the type B thymomas are derived from the cortex. Due to occasional histological overlap between the tumor subtypes creating difficulties in their separation, the aim of this study was to provide their proteomic characterization and identify potential immunohistochemical markers aiding in tissue diagnosis. Pair-wise comparison of neoplastic and normal thymus by liquid chromatography tandem mass spectrometry (LC-MS/MS of formalin fixed paraffin embedded tissue revealed 61 proteins differentially expressed in thymomas compared to normal tissue. Hierarchical clustering showed distinct segregation of subtypes AB, B1 and B2 from that of A and B3. Most notably, desmoyokin, a protein that is encoded by the AHNAK gene, was associated with type A thymomas and medulla of normal thymus, by LC-MS/MS and immunohistochemistry. In this global proteomic characterization of the thymoma, several proteins unique to different thymic compartments and thymoma subtypes were identified. Among differentially expressed proteins, desmoyokin is a marker specific for thymic medulla and is potentially promising immunohistochemical marker in separation of type A and B3 thymomas.

  12. Pre-fractionation strategies to resolve pea (Pisum sativum sub-proteomes

    Directory of Open Access Journals (Sweden)

    Claudia Nicole Meisrimler

    2015-10-01

    Full Text Available Legumes are important crop plants and pea (Pisum sativum L. has been investigated as a model with respect to several physiological aspects. The sequencing of the pea genome has not been completed. Therefore, proteomic approaches are currently limited. Nevertheless, the increasing numbers of available EST-databases as well as the high homology of the pea and medicago genome (Medicago truncatula G. allow the successful identification of proteins. Due to the un-sequenced pea genome, pre-fractionation approaches have been used in pea proteomic surveys in the past. Aside from a number of selective proteome studies on crude extracts and the chloroplast, few studies have targeted other components such as the pea secretome, an important sub-proteome of interest due to its role in abiotic and biotic stress processes. The secretome itself can be further divided into different sub-proteomes (plasma membrane, apoplast, cell wall proteins. Cell fractionation in combination with different gel-electrophoresis, chromatography methods and protein identification by mass spectrometry are important partners to gain insight into pea sub-proteomes, post-translational modifications and protein functions. Overall, pea proteomics needs to link numerous existing physiological and biochemical data to gain further insight into adaptation processes, which play important roles in field applications. Future developments and directions in pea proteomics are discussed.

  13. Endogenous structural change and climate targets: modeling experiments with Imaclim-R

    International Nuclear Information System (INIS)

    Crassous, R.; Hourcade, J.Ch.; Sassi, O.

    2006-01-01

    This paper envisages endogenous technical change as resulting from the interplay between the economic growth engine, consumption, technology and localization patterns. We perform numerical simulations with the recursive dynamic general equilibrium model IMACLIM-R to study how modeling induced technical change affects costs of CO 2 stabilization. IMACLIM-R incorporates innovative specifications about final consumption of transportation and energy to represent critical stylized facts such as rebound effects and demand induction by infrastructure and equipments. Doing so brings to light how induced technical change may not only lower stabilization costs thanks to pure technological progress, but also triggers induction of final demand - effects critical to both the level of the carbon tax and the costs of policy given a specific stabilization target. Finally, we study the sensitivity of total stabilization costs to various parameters including both technical assumptions as accelerated turnover of equipments and non-energy choices as alternative infrastructure policies. (authors)

  14. Technical advances in proteomics: new developments in data-independent acquisition [version 1; referees: 3 approved

    Directory of Open Access Journals (Sweden)

    Alex Hu

    2016-03-01

    Full Text Available The ultimate aim of proteomics is to fully identify and quantify the entire complement of proteins and post-translational modifications in biological samples of interest. For the last 15 years, liquid chromatography-tandem mass spectrometry (LC-MS/MS in data-dependent acquisition (DDA mode has been the standard for proteomics when sampling breadth and discovery were the main objectives; multiple reaction monitoring (MRM LC-MS/MS has been the standard for targeted proteomics when precise quantification, reproducibility, and validation were the main objectives. Recently, improvements in mass spectrometer design and bioinformatics algorithms have resulted in the rediscovery and development of another sampling method: data-independent acquisition (DIA. DIA comprehensively and repeatedly samples every peptide in a protein digest, producing a complex set of mass spectra that is difficult to interpret without external spectral libraries. Currently, DIA approaches the identification breadth of DDA while achieving the reproducible quantification characteristic of MRM or its newest version, parallel reaction monitoring (PRM. In comparative de novo identification and quantification studies in human cell lysates, DIA identified up to 89% of the proteins detected in a comparable DDA experiment while providing reproducible quantification of over 85% of them. DIA analysis aided by spectral libraries derived from prior DIA experiments or auxiliary DDA data produces identification and quantification as reproducible and precise as that achieved by MRM/PRM, except on low‑abundance peptides that are obscured by stronger signals. DIA is still a work in progress toward the goal of sensitive, reproducible, and precise quantification without external spectral libraries. New software tools applied to DIA analysis have to deal with deconvolution of complex spectra as well as proper filtering of false positives and false negatives. However, the future outlook is

  15. Characterization of the porcine synovial fluid proteome and a comparison to the plasma proteome

    Directory of Open Access Journals (Sweden)

    Tue Bjerg Bennike

    2015-12-01

    In addition, we analyzed the proteome of human plasma, and compared the proteomes to the obtained porcine synovial fluid proteome. The proteome of the two body fluids were found highly similar, underlining the detected plasma derived nature of many synovial fluid components. The healthy porcine synovial fluid proteomics data, human rheumatoid arthritis synovial fluid proteomics data used in the method optimization, human plasma proteomics data, and search results, have been deposited to the ProteomeXchange Consortium via the PRIDE partner repository with the dataset identifier PXD000935.

  16. Retroauricular Approach for Targeted Cochlear Therapy Experiments in Wistar Albino Rats

    Directory of Open Access Journals (Sweden)

    Selçuk Mülazımoğlu

    2017-06-01

    Full Text Available Background: As the idea of stem cell technology in the treatment of sensorial hearing loss has emerged over the past decades, the need for in vivo models for related experiments has become explicit. One of the most common experimental models for inner ear stem cell delivery experiments is the Wistar albino rat. Aims: To investigate the surgical anatomy of the temporal bone of the Wistar albino rat with respect to the dissection steps, operative techniques and potential pitfalls of surgery. Study Design: Animal experimentation. Methods: Adult Wistar albino rats were operated on via the retroauricular approach under an operation microscope. The anatomy of the temporal bone, the surgical route to the temporal bulla and the inner ear were investigated. Technical details of surgical steps, complications and potential pitfalls during the surgery were noted. Results: The study group consisted of 40 adult Wistar albino rats. The mean times to reach the bulla and to achieve cochleostomy were 4.3 (2-13 min and 7.5 min (3.5-22 min, respectively. The mean width of the facial nerve was 0.84 mm (0.42-1.25 mm. The stapedial artery lay nearly perpendicular to the course of the facial nerve (88-93 °C. There were three major complications: two large cochleostomies and one massive bleed from the stapedial artery. Conclusion: The facial nerve was the key anatomical landmark in locating the bulla. By retrograde tracing of the facial nerve, it was possible to find the bulla ventral (inferior to the main trunk. The facial nerve trunk was the upper limit when drilling the bulla. By dissecting the main trunk of the facial nerve and retracting cranially, a large drilling space could be achieved. Our results suggest that the retroauricular approach is an effective, feasible route for inner ear drug delivery experiments in Wistar albino rats

  17. Proton activation of a natural neodymium target for the SNO+ experiment

    Energy Technology Data Exchange (ETDEWEB)

    Petzoldt, Johannes; Lozza, Valentina; Zuber, Kai [Technical University of Dresden, 01069 Dresden (Germany); Lebeda, Ondrej; Stursa, Jan [Nuclear Physics Institute of the ASCR, 25068 Husinec-Rez (Czech Republic)

    2013-07-01

    In experiments searching for rare events, like the neutrinoless double beta decay, background knowledge and reduction is essential. For SNO+, the follow up of the Sudbury Neutrino Observatory experiment, the investigated transition is {sup 150}Nd → {sup 150}Sm with an estimated half-life for the 0 ν-channel of T{sub 1/2} ∼ 10{sup 25} years. SNO+ is a liquid scintillator based detector with a total mass of 780 tons. In order to study the mentioned transition, the detector will be loaded with 0.3 % natural neodymium. Even with the desired amount of 131 kg of {sup 150}Nd in SNO+, only few decays are expected. Their observation and the measured half-life would not only give an answer on the effective neutrino mass, but also to other important questions in modern neutrino physics. Long-living radioisotopes, induced by cosmogenic activation on natural Nd, contribute to the background in SNO+ and are investigated at TU Dresden. Proton activation measurements for determining the excitation functions for different isotopes in the energy range of 10 to 30 MeV were done in 2010/2011 while in 2012 the lower and higher energies were investigated. The procedure and the latest results are presented.

  18. Multiclassifier combinatorial proteomics of organelle shadows at the example of mitochondria in chromatin data.

    Science.gov (United States)

    Kustatscher, Georg; Grabowski, Piotr; Rappsilber, Juri

    2016-02-01

    Subcellular localization is an important aspect of protein function, but the protein composition of many intracellular compartments is poorly characterized. For example, many nuclear bodies are challenging to isolate biochemically and thus remain inaccessible to proteomics. Here, we explore covariation in proteomics data as an alternative route to subcellular proteomes. Rather than targeting a structure of interest biochemically, we target it by machine learning. This becomes possible by taking data obtained for one organelle and searching it for traces of another organelle. As an extreme example and proof-of-concept we predict mitochondrial proteins based on their covariation in published interphase chromatin data. We detect about ⅓ of the known mitochondrial proteins in our chromatin data, presumably most as contaminants. However, these proteins are not present at random. We show covariation of mitochondrial proteins in chromatin proteomics data. We then exploit this covariation by multiclassifier combinatorial proteomics to define a list of mitochondrial proteins. This list agrees well with different databases on mitochondrial composition. This benchmark test raises the possibility that, in principle, covariation proteomics may also be applicable to structures for which no biochemical isolation procedures are available. © 2015 The Authors. Proteomics Published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  19. Oxidative proteome alterations during skeletal muscle ageing

    Directory of Open Access Journals (Sweden)

    Sofia Lourenço dos Santos

    2015-08-01

    Full Text Available Sarcopenia corresponds to the degenerative loss of skeletal muscle mass, quality, and strength associated with ageing and leads to a progressive impairment of mobility and quality of life. However, the cellular and molecular mechanisms involved in this process are not completely understood. A hallmark of cellular and tissular ageing is the accumulation of oxidatively modified (carbonylated proteins, leading to a decreased quality of the cellular proteome that could directly impact on normal cellular functions. Although increased oxidative stress has been reported during skeletal muscle ageing, the oxidized protein targets, also referred as to the ‘oxi-proteome’ or ‘carbonylome’, have not been characterized yet. To better understand the mechanisms by which these damaged proteins build up and potentially affect muscle function, proteins targeted by these modifications have been identified in human rectus abdominis muscle obtained from young and old healthy donors using a bi-dimensional gel electrophoresis-based proteomic approach coupled with immunodetection of carbonylated proteins. Among evidenced protein spots, 17 were found as increased carbonylated in biopsies from old donors comparing to young counterparts. These proteins are involved in key cellular functions such as cellular morphology and transport, muscle contraction and energy metabolism. Importantly, impairment of these pathways has been described in skeletal muscle during ageing. Functional decline of these proteins due to irreversible oxidation may therefore impact directly on the above-mentioned pathways, hence contributing to the generation of the sarcopenic phenotype.

  20. Design and fabrication of a CH/Al dual-layer perturbation target for hydrodynamic instability experiments in ICF

    Energy Technology Data Exchange (ETDEWEB)

    Tang, Jun [Shanghai Key Laboratory of Special Artificial Microstructure Materials and Technology, School of Physics Science and Engineering, Tongji University, Shanghai 200092 (China); Xie, Zhiyong [Shanghai Institute of Laser Plasma, Shanghai 201800 (China); Du, Ai [Shanghai Key Laboratory of Special Artificial Microstructure Materials and Technology, School of Physics Science and Engineering, Tongji University, Shanghai 200092 (China); Ye, Junjian [Shanghai Institute of Laser Plasma, Shanghai 201800 (China); Zhang, Zhihua; Shen, Jun [Shanghai Key Laboratory of Special Artificial Microstructure Materials and Technology, School of Physics Science and Engineering, Tongji University, Shanghai 200092 (China); Zhou, Bin, E-mail: zhoubin863@tongji.edu.cn [Shanghai Key Laboratory of Special Artificial Microstructure Materials and Technology, School of Physics Science and Engineering, Tongji University, Shanghai 200092 (China)

    2014-04-15

    Highlights: • Sinusoidal perturbed Al foil was prepared by single-point diamond turning. • Perturbed Al foil was measured by surface profiler and white light interferometer. • Perturbed Al foil and CH layer adhered with each other via a hot-press process. • Parameters and cross-section of the CH–Al perturbation target was characterized. - Abstract: A polystyrene (CH)/aluminum (Al) dual-layer perturbation target for hydrodynamic instability experiments in inertial confinement fusion (ICF) was designed and fabricated. The target was composed of a perturbed 40 μm Al foil and a CH layer. The detailed fabrication method consisted of four steps. The 40 μm Al foil was first prepared by roll and polish process; the perturbation patterns were then introduced on the surface of the Al foil by the single-point diamond turning (SPDT) technology; the CH layer was prepared via a simple method which called spin-coating process; finally, the CH layer was directly coated on the perturbation surface of Al foil by a hot-press process to avoid the use of a sticker and to eliminate the gaps between the CH layer and the Al foil. The parameters of the target, such as the perturbation wavelength (T) and perturbation amplitude (A), were characterized by a QC-5000 tool microscope, an alpha-step 500 surface profiler and a NT1100 white light interferometer. The results showed that T and A of the target were about 52 μm and 7.34 μm, respectively. Thickness of the Al foil (H1), thickness of the CH layer (H2), and cross-section of the dual-layer target were characterized by a QC-5000 tool microscope and a scanning electron microscope (SEM). H1 and H2 were about 40 μm and 15 μm, respectively, the cross-sectional photographs of the target showed that the CH layer and the Al foil adhered perfectly with each other.

  1. [Experience of knowledge translation in the ITSAL (immigration, work and health) research project with representatives of the target population].

    Science.gov (United States)

    Ronda, Elena; López-Jacob, M José; Paredes-Carbonell, Joan J; López, Pilar; Boix, Pere; García, Ana M

    2014-01-01

    This article describes the experience of knowledge translation between researchers of the ITSAL (immigration, work and health) project and representatives of organizations working with immigrants to discuss the results obtained in the project and future research lines. A meeting was held, attended by three researchers and 18 representatives from 11 institutions. Following a presentation of the methodology and results of the project, the participants discussed the results presented and research areas of interest, thus confirming matches between the two sides and obtaining proposals of interest for the ITSAL project. We understand the process described as an approach to social validation of some of the main results of this project. This experience has allowed us to open a channel of communication with the target population of the study, in line with the necessary two-way interaction between researchers and users. Copyright © 2013 SESPAS. Published by Elsevier Espana. All rights reserved.

  2. Fixed target B experiments and the angle alpha using B0 → ππ and B0 → a1π

    International Nuclear Information System (INIS)

    McManus, A.P.; Cox, B.; Dukes, E.C.; Lawry, T.

    1993-01-01

    Fixed target beauty (B) experiments proposed at the SSC or LHC come in two basic types. The first type is the extracted beam experiments using a bent crystal of silicon or some other method to extract a beam of protons parasitically from the circulating beam as the collider experiments are taking data. The two chief experiments proposing this method are the LHB collaboration which would use the LHC at CERN and the SFT collaboration which would use the SSC. The second type of fixed target experiment is one that would place the detector around the circulating beam using a gas jet or thin wire(s) as a target. Two experiments of this type are the one proposed at CERN for LHC (GAJET) and the Hera-B experiment proposed at DESY using the Hera collider

  3. Deeply Virtual Compton Scattering off an unpolarized hydrogen target at the HERMES experiment

    Energy Technology Data Exchange (ETDEWEB)

    Zeiler, Dietmar

    2009-11-15

    The structure of this thesis is as follows: In the second chapter the theoretical basis needed for the description of the exclusive electro-production of photons in the framework of GPDs is explained. Three different models are discussed and experimental observables are defined. The third chapter includes a description of the Hermes experiment and its components. The data analysis is discussed in chapter four, along with various studies both on real and Monte Carlo data and the derivations of the systematic uncertainties. In chapter five the present results are given and interpreted both from an experimental point of view, and in comparison to existing models. Conclusion from the results are drawn. Furthermore the calibration of the Recoil Silicon Detector and the performance of the complete Recoil Detector is outlined in chapter six. In chapter seven an outlook is presented followed by the summary. (orig.)

  4. Development of aerogel-lined targets for inertial confinement fusion experiments

    Energy Technology Data Exchange (ETDEWEB)

    Braun, Tom [Technical Univ. Munchen (Germany)

    2013-03-28

    This thesis explores the formation of ICF compatible foam layers inside of an ablator shell used for inertial confinement fusion experiments at the National Ignition Facility. In particular, the capability of p- DCPD polymer aerogels to serve as a scaffold for the deuterium-tritium mix was analyzed. Four different factors were evaluated: the dependency of different factors such as thickness or composition of a precursor solution on the uniformity of the aerogel layer, how to bring the optimal composition inside of the ablator shell, the mechanical stability of ultra-low density p-DCPD aerogel bulk pieces during wetting and freezing with hydrogen, and the wetting behavior of thin polymer foam layers in HDC carbon ablator shells with liquid deuterium. The research for thesis was done at Lawrence Livermore National Laboratory in cooperation with the Technical University Munich.

  5. Deeply Virtual Compton Scattering off an unpolarized hydrogen target at the HERMES experiment

    International Nuclear Information System (INIS)

    Zeiler, Dietmar

    2009-11-01

    The structure of this thesis is as follows: In the second chapter the theoretical basis needed for the description of the exclusive electro-production of photons in the framework of GPDs is explained. Three different models are discussed and experimental observables are defined. The third chapter includes a description of the Hermes experiment and its components. The data analysis is discussed in chapter four, along with various studies both on real and Monte Carlo data and the derivations of the systematic uncertainties. In chapter five the present results are given and interpreted both from an experimental point of view, and in comparison to existing models. Conclusion from the results are drawn. Furthermore the calibration of the Recoil Silicon Detector and the performance of the complete Recoil Detector is outlined in chapter six. In chapter seven an outlook is presented followed by the summary. (orig.)

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

    Science.gov (United States)

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

    2017-01-01

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

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

    Science.gov (United States)

    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 .

  8. Proteomics of Skeletal Muscle

    DEFF Research Database (Denmark)

    Deshmukh, Atul

    2016-01-01

    , of altered protein expressions profiles and/or their posttranslational modifications (PTMs). Mass spectrometry (MS)-based proteomics offer enormous promise for investigating the molecular mechanisms underlying skeletal muscle insulin resistance and exercise-induced adaptation; however, skeletal muscle......Skeletal muscle is the largest tissue in the human body and plays an important role in locomotion and whole body metabolism. It accounts for ~80% of insulin stimulated glucose disposal. Skeletal muscle insulin resistance, a primary feature of Type 2 diabetes, is caused by a decreased ability...... of muscle to respond to circulating insulin. Physical exercise improves insulin sensitivity and whole body metabolism and remains one of the most promising interventions for the prevention of Type 2 diabetes. Insulin resistance and exercise adaptations in skeletal muscle might be a cause, or consequence...

  9. A Model for the Application of Target-Controlled Intravenous Infusion for a Prolonged Immersive DMT Psychedelic Experience

    Directory of Open Access Journals (Sweden)

    Andrew Robert Gallimore

    2016-07-01

    Full Text Available The state of consciousness induced by N,N-dimethyltryptamine (DMT is one of the most extraordinary of any naturally-occurring psychedelic substance. Users consistently report the complete replacement of normal subjective experience with a novel alternate universe, often densely populated with a variety of strange objects and other highly complex visual content, including what appear to be sentient beings. The phenomenology of the DMT state is of great interest to psychology and calls for rigorous academic enquiry. The extremely short duration of DMT effects—less than 20 minutes—militates against single dose administration as the ideal model for such enquiry. Using pharmacokinetic modelling and DMT blood sampling data, we demonstrate that the unique pharmacological characteristics of DMT, which also include a rapid onset and lack of acute tolerance to its subjective effects, make it amenable to administration by target-controlled intravenous infusion. This is a technology developed to maintain a stable brain concentration of anaesthetic drugs during surgery. Simulations of our model demonstrate that this approach will allow research subjects to be induced into a stable and prolonged DMT experience, making it possible to carefully observe its psychological contents, and provide more extensive accounts for subsequent analyses. This model would also be valuable in performing functional neuroimaging, where subjects are required to remain under the influence of the drug for extended periods. Finally, target-controlled intravenous infusion of DMT may aid the development of unique psychotherapeutic applications of this psychedelic agent.

  10. The Succinated Proteome

    Energy Technology Data Exchange (ETDEWEB)

    Merkley, Eric D.; Metz, Thomas O.; Smith, Richard D.; Baynes, John; Frizell, Norma

    2014-03-30

    Succination is a chemical modification of cysteine in protein by the Krebs cycle intermediate, fumarate, yielding S-(2-succino)cysteine (2SC). Intracellular fumarate concentration and succination of proteins are increased by hyperpolarization of the inner mitochondrial membrane, in concert with mitochondrial, endoplasmic reticulum (ER) and oxidative stress in adipocytes grown in high glucose medium and in adipose tissue in obesity and diabetes. Increased succination of proteins is also detected in the kidney of a fumarase conditional knock-out mouse which develops renal tumors. Keap1, the gatekeeper of the antioxidant response, was identified as a major succinated protein in renal cancer cells, suggesting that succination may play a role in activation of the antioxidant response. A wide range of proteins is subject to succination, including enzymes, adipokines, cytoskeletal proteins and ER chaperones with functional cysteine residues. There is also significant overlap between succinated and glutathionylated proteins, and with proteins containing cysteine residues that are readily oxidized to the sulfenic (cysteic) acid. Succination of adipocyte proteins is inhibited by uncouplers, which discharge the mitochondrial membrane potential (Δψm) and by ER stress inhibitors. 2SC serves as a biomarker of mitochondrial stress or dysfunction in chronic diseases, such as obesity, diabetes and cancer, and recent studies suggest that succination is a mechanistic link between mitochondrial dysfunction, oxidative and ER stress, and cellular progression toward apoptosis. In this article, we review the history of the succinated proteome and the challenges associated with measuring this non-enzymatic post-translational modification of proteins by proteomics approaches.

  11. BioinformatiqTM - integrating data types for proteomic discovery

    International Nuclear Information System (INIS)

    Arthur, J.W.; Harrison, M.; Manoharan, A.; Traini, M.; Shaw, E.; Wilkins, M.

    2001-01-01

    Proteomics (Wilkins et al. 1997) involves the large-scale analysis of expressed proteins. At each stage of the discovery process the researcher accumulates large volumes of data. These include: clinical or biological data about the sample being studied; details of sample purification and separation; images of 2D gels and associated information; MALDI mass spectra; MS/MS and PSD spectra; as well as meta-data relating to the projects undertaken and experiments performed. All this must be combined with existing databases of protein and EST sequences, post-translational modifications, and protein glycosylation, then processed with sophisticated bioinformatics tools in order to extract meaningful answers to questions of biological, clinical, and agricultural significance. BioinformatlQ TM is a web-based application for the storage, management, and automated bioinformatic analysis of proteomic information. This poster will demonstrate the integration of these disparate data sources in proteomics

  12. Investigating the empirical support for therapeutic targets proposed by the temporal experience of pleasure model in schizophrenia: A systematic review.

    Science.gov (United States)

    Edwards, Clementine J; Cella, Matteo; Tarrier, Nicholas; Wykes, Til

    2015-10-01

    Anhedonia and amotivation are substantial predictors of poor functional outcomes in people with schizophrenia and often present a formidable barrier to returning to work or building relationships. The Temporal Experience of Pleasure Model proposes constructs which should be considered therapeutic targets for these symptoms in schizophrenia e.g. anticipatory pleasure, memory, executive functions, motivation and behaviours related to the activity. Recent reviews have highlighted the need for a clear evidence base to drive the development of targeted interventions. To review systematically the empirical evidence for each TEP model component and propose evidence-based therapeutic targets for anhedonia and amotivation in schizophrenia. Following PRISMA guidelines, PubMed and PsycInfo were searched using the terms "schizophrenia" and "anhedonia". Studies were included if they measured anhedonia and participants had a diagnosis of schizophrenia. The methodology, measures and main findings from each study were extracted and critically summarised for each TEP model construct. 80 independent studies were reviewed and executive functions, emotional memory and the translation of motivation into actions are highlighted as key deficits with a strong evidence base in people with schizophrenia. However, there are many relationships that are unclear because the empirical work is limited by over-general tasks and measures. Promising methods for research which have more ecological validity include experience sampling and behavioural tasks assessing motivation. Specific adaptations to Cognitive Remediation Therapy, Cognitive Behavioural Therapy and the utilisation of mobile technology to enhance representations and emotional memory are recommended for future development. Copyright © 2015. Published by Elsevier B.V.

  13. Application of proteomics to translational research

    International Nuclear Information System (INIS)

    Liotta, L.A.; Petricoin, E.; Garaci, E.; De Maria, R.; Belluco, C.

    2009-01-01

    Deriving public benefit from basic biomedical research requires a dedicated and highly coordinated effort between basic scientists, physicians, bioinformaticians, clinical trial coordinators, MD and PhD trainees and fellows, and a host of other skilled participants. The Istituto Superiore di Sanita/George Mason University US-Italy Oncoproteomics program, established in 2005, is a successful example of a synergistic creative collaboration between basic scientists and clinical investigators conducting translational research. This program focuses on the application of the new field of proteomics to three urgent and fundamental clinical needs in cancer medicine: 1.) Biomarkers for early diagnosis of cancer, when it is still treatable, 2.) Individualizing patient therapy for molecular targeted inhibitors that block signal pathways driving cancer pathogenesis and 3.) Cancer Progenitor Cells (CSCs): When do the lethal progenitors of cancer first emerge, and how can we treat these CSCs with molecular targeted inhibitors

  14. An individual urinary proteome analysis in normal human beings to define the minimal sample number to represent the normal urinary proteome

    Directory of Open Access Journals (Sweden)

    Liu Xuejiao

    2012-11-01

    Full Text Available Abstract Background The urinary proteome has been widely used for biomarker discovery. A urinary proteome database from normal humans can provide a background for discovery proteomics and candidate proteins/peptides for targeted proteomics. Therefore, it is necessary to define the minimum number of individuals required for sampling to represent the normal urinary proteome. Methods In this study, inter-individual and inter-gender variations of urinary proteome were taken into consideration to achieve a representative database. An individual analysis was performed on overnight urine samples from 20 normal volunteers (10 males and 10 females by 1DLC/MS/MS. To obtain a representative result of each sample, a replicate 1DLCMS/MS analysis was performed. The minimal sample number was estimated by statistical analysis. Results For qualitative analysis, less than 5% of new proteins/peptides were identified in a male/female normal group by adding a new sample when the sample number exceeded nine. In addition, in a normal group, the percentage of newly identified proteins/peptides was less than 5% upon adding a new sample when the sample number reached 10. Furthermore, a statistical analysis indicated that urinary proteomes from normal males and females showed different patterns. For quantitative analysis, the variation of protein abundance was defined by spectrum count and western blotting methods. And then the minimal sample number for quantitative proteomic analysis was identified. Conclusions For qualitative analysis, when considering the inter-individual and inter-gender variations, the minimum sample number is 10 and requires a balanced number of males and females in order to obtain a representative normal human urinary proteome. For quantitative analysis, the minimal sample number is much greater than that for qualitative analysis and depends on the experimental methods used for quantification.

  15. VIDEO: Dr. Henry Rodriguez - Proteogenomics in Cancer Medicine | Office of Cancer Clinical Proteomics Research

    Science.gov (United States)

    Dr. Henry Rodriguez, director of the Office of Cancer Clinical Proteomics Research (OCCPR) at NCI, speaks with ecancer television at WIN 2017 about the translation of the proteins expressed in a patient's tumor into a map for druggable targets. By combining genomic and proteomic information (proteogenomics), leading scientists are gaining new insights into ways to detect and treat cancer due to a more complete and unified understanding of complex biological processes.

  16. The single lineup paradigm: A new way to manipulate target presence in eyewitness identification experiments.

    Science.gov (United States)

    Oriet, Chris; Fitzgerald, Ryan J

    2018-02-01

    The suspect in eyewitness lineups may be guilty or innocent. These possibilities are traditionally simulated in eyewitness identification studies using a dual-lineup paradigm: All witnesses observe the same perpetrator and then receive one of two lineups. In this paradigm, the suspect's guilt is manipulated by including the perpetrator in one lineup and an innocent suspect in the other. The lineup is then filled with people matched to either the suspect (resulting in different fillers in perpetrator-present and perpetrator-absent lineups) or to the perpetrator (resulting in the same fillers in each lineup). An inescapable feature of the dual-lineup paradigm is that the perpetrator-present and perpetrator-absent lineups differ not only in the suspect's guilt, but also in their composition. Here, we describe a single-lineup paradigm: Subjects observe one of two perpetrators and then all subjects receive the same lineup containing one of the perpetrators. This alternative paradigm allows manipulation of the suspect's guilt without changing the lineup's composition. In three experiments, we applied the single-lineup paradigm to explore suspect-filler similarity and consistently found that increasing similarity reduced perpetrator identifications but did little to prevent innocent suspect misidentifications. Conversely, when fillers were matched to the perpetrator using a dual-lineup paradigm, increasing similarity reduced identification of perpetrators and innocent suspects. This finding suggests that the effect of filler similarity may depend on the person to whom the fillers are matched. We suggest that the single-lineup paradigm is a more ecologically valid and better controlled approach to creating suspect-matched lineups in laboratory investigations of eyewitness memory than existing procedures. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

  17. Targeted removal of ant colonies in ecological experiments, using hot water.

    Science.gov (United States)

    Tschinkel, Walter R; King, Joshua R

    2007-01-01

    Ecological experiments on fire ants cannot, or should not, use poison baits to eliminate the fire ants because such baits are not specific to fire ants, or even to ants. Hot water is an extremely effective and specific killing agent for fire ant colonies, but producing large amounts of hot water in the field, and making the production apparatus mobile have been problematical. The construction and use of a charcoal-fired kiln made from a 55-gal. oil drum lined with a sand-fireclay mixture is described. An automobile heater fan powered from a 12-v battery provided a draft. Dual bilge pumps pumped water from a large tank through a long coil of copper tubing within the kiln to produce 4 to 5 l. of hot water per min. The hot water was collected in 20 l. buckets and poured into fire ant nests previously opened by piercing with a stick. The entire assembly was transported in and operated from the back of a pickup truck. Five experimental plots containing 32 to 38 colonies of the fire ant, Solenopsis invicta, Buren (Hymenoptera: Formicidae), were treated with hot water over a period of two years. All colonies on the treatment plots were treated twice with hot water early in 2004, reducing their numbers to zero. However new colonies were formed, and mature colonies expanded into the plots. A third treatment was made in the spring of 2005, after which fire ant populations were suppressed for over a year. Whereas the 5 control plots contained a total of 166 mostly large colonies, the 5 treatment plots contained no live colonies at all. Averaged over a two-year period, a 70% reduction in total number of colonies was achieved (P ants.

  18. Quantitative Proteomic Analysis of Optimal Cutting Temperature (OCT) Embedded Core-Needle Biopsy of Lung Cancer

    Science.gov (United States)

    Zhao, Xiaozheng; Huffman, Kenneth E.; Fujimoto, Junya; Canales, Jamie Rodriguez; Girard, Luc; Nie, Guangjun; Heymach, John V.; Wistuba, Igacio I.; Minna, John D.; Yu, Yonghao

    2017-10-01

    With recent advances in understanding the genomic underpinnings and oncogenic drivers of pathogenesis in different subtypes, it is increasingly clear that proper pretreatment diagnostics are essential for the choice of appropriate treatment options for non-small cell lung cancer (NSCLC). Tumor tissue preservation in optimal cutting temperature (OCT) compound is commonly used in the surgical suite. However, proteins recovered from OCT-embedded specimens pose a challenge for LC-MS/MS experiments, due to the large amounts of polymers present in OCT. Here we present a simple workflow for whole proteome analysis of OCT-embedded NSCLC tissue samples, which involves a simple trichloroacetic acid precipitation step. Comparisons of protein recovery between frozen versus OCT-embedded tissue showed excellent consistency with more than 9200 proteins identified. Using an isobaric labeling strategy, we quantified more than 5400 proteins in tumor versus normal OCT-embedded core needle biopsy samples. Gene ontology analysis indicated that a number of proliferative as well as squamous cell carcinoma (SqCC) marker proteins were overexpressed in the tumor, consistent with the patient's pathology based diagnosis of "poorly differentiated SqCC". Among the most downregulated proteins in the tumor sample, we noted a number of proteins with potential immunomodulatory functions. Finally, interrogation of the aberrantly expressed proteins using a candidate approach and cross-referencing with publicly available databases led to the identification of potential druggable targets in DNA replication and DNA damage repair pathways. We conclude that our approach allows LC-MS/MS proteomic analyses on OCT-embedded lung cancer specimens, opening the way to bring powerful proteomics into the clinic. [Figure not available: see fulltext.

  19. The Effect of Ambient Temperatures of Two Threatened Caribbean Coral Species: a Proteomic Study

    Science.gov (United States)

    Ricaurte, M.; Schizas, N. V.; Weil, E.; Ciborowski, P.; Boukli, N. M.

    2016-02-01

    Coral reefs are among the most valuable ecosystems on the earth. Increasing water temperatures as a consequence of global warming have been identified, as an overriding cause of coral decline (e.g. increased incidence of diseases, bleaching), and one of the regions that has been identified vulnerable to climatic changes, is the Caribbean. Laboratory experiments have shown negative effects of different temperatures in coral growth, larval and adult survival, and gene expression. In order to understand the molecular and cellular basis in the protein regulation during changes in temperature in the field, a comparative proteomic analysis associated with thermal fluctuations was made from wet and dry season of 2014. In the study, we investigated alterations in proteins of Acropora palmata and Orbicella faveolata by two-dimensional gel electrophoresis (2D-GE) followed by liquid chromatography-tandem mass spectrometry, protein identification, and confirmation at the gene expression level by qRT-PCR.Proteomes of related samples demonstrated 195 differentially expressed proteins (DEP) in A. palmata during dry season and 108 (DEP) during wet season of 2014. O. faveolata overexpressed 62 (DEP) in dry season and 190 (DEP) during wet season of 2014. All proteins had a two-fold or greater change in expression due to temperature, altering several components of the cellular stress response that include chaperones, stress proteins, antioxidant enzymes, proteases, cytoskeletal and apoptosis regulating proteins. Our results suggest that A. palmata and O. faveolata display a distinct response by expressing these key protein signatures in dry and wet season. This proteomic approach may open new avenues of research to detect potential early biomarkers involved in response to these stressors, during seasonal changes in water temperatures. The results provide insight into targets and mechanistic strategies to detect potential markers involved in response to temperature change for A

  20. High energy density physics effects predicted in simulations of the CERN HiRadMat beam-target interaction experiments

    Science.gov (United States)

    Tahir, N. A.; Burkart, F.; Schmidt, R.; Shutov, A.; Wollmann, D.; Piriz, A. R.

    2016-12-01

    Experiments have been done at the CERN HiRadMat (High Radiation to Materials) facility in which large cylindrical copper targets were irradiated with 440 GeV proton beam generated by the Super Proton Synchrotron (SPS). The primary purpose of these experiments was to confirm the existence of hydrodynamic tunneling of ultra-relativistic protons and their hadronic shower in solid materials, that was predicted by previous numerical simulations. The experimental measurements have shown very good agreement with the simulation results. This provides confidence in our simulations of the interaction of the 7 TeV LHC (Large Hadron Collider) protons and the 50 TeV Future Circular Collider (FCC) protons with solid materials, respectively. This work is important from the machine protection point of view. The numerical simulations have also shown that in the HiRadMat experiments, a significant part of thetarget material is be converted into different phases of High Energy Density (HED) matter, including two-phase solid-liquid mixture, expanded as well as compressed hot liquid phases, two-phase liquid-gas mixture and gaseous state. The HiRadMat facility is therefore a unique ion beam facility worldwide that is currently available for studying the thermophysical properties of HED matter. In the present paper we discuss the numerical simulation results and present a comparison with the experimental measurements.

  1. The AFIS experiment: Detecting low energetic antiprotons in a low earth orbit, using an active target detector

    Energy Technology Data Exchange (ETDEWEB)

    Poeschl, Thomas; Gaisbauer, Dominic; Greenwald, Daniel; Hahn, Alexander; Hauptmann, Philipp; Konorov, Igor; Meng, Lingxin; Paul, Stephan [Physics Department E18, Technische Universitaet Muenchen (Germany); Losekamm, Martin [Physics Department E18, Technische Universitaet Muenchen (Germany); Institute of Astronautics, Technische Universitaet Muenchen (Germany); Renker, Dieter [Physics Department E17, Technische Universitaet Muenchen (Germany)

    2014-07-01

    Since the first observation of geomagnetically trapped antiprotons by the PAMELA experiment and the new results on the positron excess by the AMS-02 experiment, the creation and transport of antimatter in the Earth's upper atmosphere attracts more and more attention both at theoretical and experimental side. For this reason the AFIS experiment was initiated to measure the flux of low energetic antiprotons in the South Atlantic Anomaly (SAA). We developed an active target detector made from scintillating fibers connected to silicon photomultipliers which allows to detect antiprotons in the energy interval of about 30 MeV-100 MeV. The stopping curve of incoming antiprotons (Bragg peak) and the signal of outgoing pions created from the annihilation, are used for particle identification as well as triggering. We plan to implement this detector on a 3 unit cubesat satellite in the framework the 'Move2Warp' mission, which is carried out as a student project by the Technische Universitaet Muenchen.

  2. Novel uses of a wide beam saddle field ion source for producing targets used in nuclear physics experiments at the Argonne National Laboratory ATLAS facility

    International Nuclear Information System (INIS)

    Greene, J.P.; Thomas, G.E.

    1996-01-01

    The wide beam ion sputter source has several unique characteristics which make it very useful for producing, reducing the thickness or cleaning the surface of targets needed for nuclear physics experiments. A discussion of these techniques as well as the sputter source characteristics will be given. Sputter yields obtained utilizing the source are presented for a variety of materials common to nuclear target production

  3. Proteomic analysis of human tooth pulp: proteomics of human tooth.

    Science.gov (United States)

    Eckhardt, Adam; Jágr, Michal; Pataridis, Statis; Mikšík, Ivan

    2014-12-01

    The unique pulp-dentin complex demonstrates strong regenerative potential, which enables it to respond to disease and traumatic injury. Identifying the proteins of the pulp-dentin complex is crucial to understanding the mechanisms of regeneration, tissue calcification, defense processes, and the reparation of dentin by dental pulp. The lack of knowledge of these proteins limits the development of more efficient therapies. The proteomic profile of human tooth pulp was investigated and compared with the proteome of human dentin and blood. The samples of tooth pulp were obtained from 5 sound permanent human third molars of 5 adults (n = 5). The extracted proteins were separated by 2-dimensional gel electrophoresis, analyzed by nano-liquid chromatography tandem mass spectrometry, and identified by correlating mass spectra to the proteomic databases. A total of 342 proteins were identified with high confidence, and 2 proteins were detected for the first time in an actual human sample. The identified tooth pulp proteins have a variety of functions: structural, catalytic, transporter, protease activity, immune response, and many others. In a comparison with dentin and blood plasma, 140 (pulp/dentin) shared proteins were identified, 37 of which were not observed in plasma. It can be suggested that they might participate in the unique pulp-dentin complex. This proteomic investigation of human tooth pulp, together with the previously published study of human dentin, is one of the most comprehensive proteome lists of human teeth to date. Copyright © 2014 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

  4. Semen proteomics and male infertility.

    Science.gov (United States)

    Jodar, Meritxell; Soler-Ventura, Ada; Oliva, Rafael

    2017-06-06

    Semen is a complex body fluid containing an admixture of spermatozoa suspended in secretions from the testes and epididymis which are mixed at the time of ejaculation with secretions from other accessory sex glands such as the prostate and seminal vesicles. High-throughput technologies have revealed that, contrary to the idea that sperm cells are simply a silent delivery vehicle of the male genome to the oocyte, the sperm cells in fact provide both a specific epigenetically marked DNA together with a complex population of proteins and RNAs crucial for embryogenesis. Similarly, -omic technologies have also enlightened that seminal fluid seems to play a much greater role than simply being a medium to carry the spermatozoa through the female reproductive tract. In the present review, we briefly overview the sperm cell biology, consider the key issues in sperm and seminal fluid sample preparation for high-throughput proteomic studies, describe the current state of the sperm and seminal fluid proteomes generated by high-throughput proteomic technologies and provide new insights into the potential communication between sperm and seminal fluid. In addition, comparative proteomic studies open a window to explore the potential pathogenic mechanisms of infertility and the discovery of potential biomarkers with clinical significance. The review updates the numerous proteomics studies performed on semen, including spermatozoa and seminal fluid. In addition, an integrative analysis of the testes, sperm and seminal fluid proteomes is also included providing insights into the molecular mechanisms that regulate the generation, maturation and transit of spermatozoa. Furthermore, the compilation of several differential proteomic studies focused on male infertility reveals potential pathways disturbed in specific subtypes of male infertility and points out towards future research directions in the field. Copyright © 2016 Elsevier B.V. All rights reserved.

  5. Spaceflight induced changes in the human proteome.

    Science.gov (United States)

    Kononikhin, Alexey S; Starodubtseva, Natalia L; Pastushkova, Lyudmila Kh; Kashirina, Daria N; Fedorchenko, Kristina Yu; Brhozovsky, Alexander G; Popov, Igor A; Larina, Irina M; Nikolaev, Evgeny N

    2017-01-01

    Spaceflight is one of the most extreme conditions encountered by humans: Individuals are exposed to radiation, microgravity, hypodynamia, and will experience isolation. A better understanding of the molecular processes induced by these factors may allow us to develop personalized countermeasures to minimize risks to astronauts. Areas covered: This review is a summary of literature searches from PubMed, NASA, Roskosmos and the authors' research experiences and opinions. The review covers the available proteomic data on the effects of spaceflight factors on the human body, including both real space missions and ground-based model experiments. Expert commentary: Overall, the authors believe that the present background, methodology and equipment improvements will enhance spaceflight safety and support accumulation of new knowledge on how organisms adapt to extreme conditions.

  6. Proteomics in evolutionary ecology.

    Science.gov (United States)

    Baer, B; Millar, A H

    2016-03-01

    Evolutionary ecologists are traditionally gene-focused, as genes propagate phenotypic traits across generations and mutations and recombination in the DNA generate genetic diversity required for evolutionary processes. As a consequence, the inheritance of changed DNA provides a molecular explanation for the functional changes associated with natural selection. A direct focus on proteins on the other hand, the actual molecular agents responsible for the expression of a phenotypic trait, receives far less interest from ecologists and evolutionary biologists. This is partially due to the central dogma of molecular biology that appears to define proteins as the 'dead-end of molecular information flow' as well as technical limitations in identifying and studying proteins and their diversity in the field and in many of the more exotic genera often favored in ecological studies. Here we provide an overview of a newly forming field of research that we refer to as 'Evolutionary Proteomics'. We point out that the origins of cellular function are related to the properties of polypeptide and RNA and their interactions with the environment, rather than DNA descent, and that the critical role of horizontal gene transfer in evolution is more about coopting new proteins to impact cellular processes than it is about modifying gene function. Furthermore, post-transcriptional and post-translational processes generate a remarkable diversity of mature proteins from a single gene, and the properties of these mature proteins can also influence inheritance through genetic and perhaps epigenetic mechanisms. The influence of post-transcriptional diversification on evolutionary processes could provide a novel mechanistic underpinning for elements of rapid, directed evolutionary changes and adaptations as observed for a variety of evolutionary processes. Modern state-of the art technologies based on mass spectrometry are now available to identify and quantify peptides, proteins, protein

  7. Studies of the LBL CMOS integrated amplifier/discriminator for randomly timed inputs from fixed target experiments

    International Nuclear Information System (INIS)

    Russ, J.S.; Yarema, R.J.; Zimmerman, T.

    1988-12-01

    A group at Lawrence Berkeley Laboratory has reported an elegant CMOS VLSI circuit for amplifying, discriminating, and encoding the signals from highly-segmented charge output devices, e.g., silicon strip detectors or pad readout structures in gaseous detectors. The design exploits switched capacitor circuits and the well-known time structure of data acquisition in colliding beam accelerators to cancel leakage effects and switching noise. For random inputs, these methods are not directly applicable. However, the high speed of the reset switches makes possible a mode of operation for fixed target experiments that uses fast resets to erase unwanted data from random triggers. Data acquisition in this mode has been performed. Details of operation and measurements of noise and rate capability will be presented. 8 refs., 6 figs

  8. Cross Sections for Neutron-induced Reactions on Actinide Targets Extracted from Surrogate Experiments: A Status Report

    Energy Technology Data Exchange (ETDEWEB)

    Escher, J E; Burke, J T; Dietrich, F S; Lesher, S R; Scielzo, N D; Thompson, I J; Younes, W

    2009-10-01

    The Surrogate nuclear reactions method, an indirect approach for determining cross sections for compound-nuclear reactions involving difficult-to-measure targets, is reviewed. Focusing on cross sections for neutron-induced reactions on actinides, we review the successes of past and present applications of the method and assess its uncertainties and limitations. The approximations used in the analyses of most experiments work reasonably well for (n,f) cross sections for neutron energies above 1-2 MeV, but lead to discrepancies for low-energy (n,f) reactions, as well as for (n,{gamma}) applications. Correcting for some of the effects neglected in the approximate analyses leads to improved (n,f) results. We outline steps that will further improve the accuracy and reliability of the Surrogate method and extend its applicability to reactions that cannot be approached with the present implementation of the method.

  9. Cross Sections for Neutron-induced Reactions on Actinide Targets Extracted from Surrogate Experiments: A Status Report

    International Nuclear Information System (INIS)

    Escher, J.E.; Burke, J.T.; Dietrich, F.S.; Lesher, S.R.; Scielzo, N.D.; Thompson, I.J.; Younes, W.

    2009-01-01

    The Surrogate nuclear reactions method, an indirect approach for determining cross sections for compound-nuclear reactions involving difficult-to-measure targets, is reviewed. Focusing on cross sections for neutron-induced reactions on actinides, we review the successes of past and present applications of the method and assess its uncertainties and limitations. The approximations used in the analyses of most experiments work reasonably well for (n,f) cross sections for neutron energies above 1-2 MeV, but lead to discrepancies for low-energy (n,f) reactions, as well as for (n,γ) applications. Correcting for some of the effects neglected in the approximate analyses leads to improved (n,f) results. We outline steps that will further improve the accuracy and reliability of the Surrogate method and extend its applicability to reactions that cannot be approached with the present implementation of the method.

  10. Target laboratory

    International Nuclear Information System (INIS)

    Ephraim, D.C.; Pednekar, A.R.

    1993-01-01

    A target laboratory to make stripper foils for the accelerator and various targets for use in the experiments is set up in the pelletron accelerator facility. The facilities available in the laboratory are: (1) D.C. glow discharge setup, (2) carbon arc set up, and (3) vacuum evaporation set up (resistance heating), electron beam source, rolling mill - all for target preparation. They are described. Centrifugal deposition technique is used for target preparation. (author). 3 figs

  11. First systematic plant proteomics workshop in Botany Department, University of Delhi: transferring proteomics knowledge to next-generation researchers and students.

    Science.gov (United States)

    Deswal, Renu; Abat, Jasmeet Kaur; Sehrawat, Ankita; Gupta, Ravi; Kashyap, Prakriti; Sharma, Shruti; Sharma, Bhavana; Chaurasia, Satya Prakash; Chanu, Sougrakpam Yaiphabi; Masi, Antonio; Agrawal, Ganesh Kumar; Sarkar, Abhijit; Agrawal, Raj; Dunn, Michael J; Renaut, Jenny; Rakwal, Randeep

    2014-07-01

    International Plant Proteomics Organization (INPPO) outlined ten initiatives to promote plant proteomics in each and every country. With greater emphasis in developing countries, one of those was to "organize workshops at national and international levels to train manpower and exchange information". This third INPPO highlights covers the workshop organized for the very first time in a developing country, India, at the Department of Botany in University of Delhi on December 26-30, 2013 titled - "1(st) Plant Proteomics Workshop / Training Program" under the umbrella of INPPO India-Nepal chapter. Selected 20 participants received on-hand training mainly on gel-based proteomics approach along with manual booklet and parallel lectures on this and associated topics. In house, as well as invited experts drawn from other Universities and Institutes (national and international), delivered talks on different aspects of gel-based and gel-free proteomics. Importance of gel-free proteomics approach, translational proteomics, and INPPO roles were presented and interactively discussed by a group of three invited speakers Drs. Ganesh Kumar Agrawal (Nepal), Randeep Rakwal (Japan), and Antonio Masi (Italy). Given the output of this systematic workshop, it was proposed and thereafter decided to be organized every alternate year; the next workshop will be held in 2015. Furthermore, possibilities on providing advanced training to those students / researchers / teachers with basic knowledge in proteomics theory and experiments at national and international levels were discussed. INPPO is committed to generating next-generation trained manpower in proteomics, and it would only happen by the firm determination of scientists to come forward and do it. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  12. Target-plasma production by laser irradiation of a pellet in the Baseball II-T experiment

    International Nuclear Information System (INIS)

    Damm, C.C.; Foote, J.H.; Futch, A.H.; Goodman, R.K.; Hornady, R.S.; Osher, J.E.; Porter, G.D.

    1977-01-01

    One way to generate a plasma target that can be used in conjunction with an injected neutral beam to initiate a high-energy plasma in a steady-state, magnetic-mirror field is by the laser irradiation of a solid pellet located within the confinement region. In the Lawrence Livermore Laboratory Baseball II-T experiment, a CO 2 laser was used to provide a two-sided irradiation of an ammonia pellet; the maximum laser intensity on the pellet was approximately 4 x 10 12 W/cm 2 . The 150-μm-dia pellets were guided to the laser focal spot in the Baseball II-T magnetic field using steering voltages controlled by a microcomputer-based system. Diagnostics showed complete ionization of the pellet, average ion energies in the keV range, synchronized triggering of the laser and the neutral beam, and rapid expansion of the plasma to a diameter that was a good match to the diameter of the neutral beam. Predictions obtained from the LASNEX code compared well with measured results. Although the laser-pellet approach was proven usable as a target-plasma startup system, it would be much more complicated and expensive than the method in which streaming plasma is used to trap the neutal beams

  13. Implant-assisted magnetic drug targeting in permeable microvessels: Comparison of two-fluid statistical transport model with experiment

    Energy Technology Data Exchange (ETDEWEB)

    ChiBin, Zhang; XiaoHui, Lin, E-mail: lxh60@seu.edu.cn; ZhaoMin, Wang; ChangBao, Wang

    2017-03-15

    In experiments and theoretical analyses, this study examines the capture efficiency (CE) of magnetic drug carrier particles (MDCPs) for implant-assisted magnetic drug targeting (IA-MDT) in microvessels. It also proposes a three-dimensional statistical transport model of MDCPs for IA-MDT in permeable microvessels, which describes blood flow by the two-fluid (Casson and Newtonian) model. The model accounts for the permeable effect of the microvessel wall and the coupling effect between the blood flow and tissue fluid flow. The MDCPs move randomly through the microvessel, and their transport state is described by the Boltzmann equation. The regulated changes and factors affecting the CE of the MDCPs in the assisted magnetic targeting were obtained by solving the theoretical model and by experimental testing. The CE was negatively correlated with the blood flow velocity, and positively correlated with the external magnetic field intensity and microvessel permeability. The predicted CEs of the MDCPs were consistent with the experimental results. Additionally, under the same external magnetic field, the predicted CE was 5–8% higher in the IA-MDT model than in the model ignoring the permeability effect of the microvessel wall. - Highlights: • A model of MDCPs for IA-MDT in permeable microvessels was established. • An experimental device was established, the CE of MDCPs was measured. • The predicted CE of MDCPs was 5–8% higher in the IA-MDT model.

  14. Proteomic Analysis of Chinese Hamster Ovary Cells

    DEFF Research Database (Denmark)

    Baycin-Hizal, Deniz; Tabb, David L.; Chaerkady, Raghothama

    2012-01-01

    To complement the recent genomic sequencing of Chinese hamster ovary (CHO) cells, proteomic analysis was performed on CHO cells including the cellular proteome, secretome, and glycoproteome using tandem mass spectrometry (MS/MS) of multiple fractions obtained from gel electrophoresis, multidimens......To complement the recent genomic sequencing of Chinese hamster ovary (CHO) cells, proteomic analysis was performed on CHO cells including the cellular proteome, secretome, and glycoproteome using tandem mass spectrometry (MS/MS) of multiple fractions obtained from gel electrophoresis...

  15. An introduction to statistical process control in research proteomics.

    Science.gov (United States)

    Bramwell, David

    2013-12-16

    Statistical process control is a well-established and respected method which provides a general purpose, and consistent framework for monitoring and improving the quality of a process. It is routinely used in many industries where the quality of final products is critical and is often required in clinical diagnostic laboratories [1,2]. To date, the methodology has been little utilised in research proteomics. It has been shown to be capable of delivering quantitative QC procedures for qualitative clinical assays [3] making it an ideal methodology to apply to this area of biological research. To introduce statistical process control as an objective strategy for quality control and show how it could be used to benefit proteomics researchers and enhance the quality of the results they generate. We demonstrate that rules which provide basic quality control are easy to derive and implement and could have a major impact on data quality for many studies. Statistical process control is a powerful tool for investigating and improving proteomics research work-flows. The process of characterising measurement systems and defining control rules forces the exploration of key questions that can lead to significant improvements in performance. This work asserts that QC is essential to proteomics discovery experiments. Every experimenter must know the current capabilities of their measurement system and have an objective means for tracking and ensuring that performance. Proteomic analysis work-flows are complicated and multi-variate. QC is critical for clinical chemistry measurements and huge strides have been made in ensuring the quality and validity of results in clinical biochemistry labs. This work introduces some of these QC concepts and works to bridge their use from single analyte QC to applications in multi-analyte systems. This article is part of a Special Issue entitled: Standardization and Quality Control in Proteomics. Copyright © 2013 The Author. Published by Elsevier

  16. Maillard Proteomics: Opening New Pages

    Directory of Open Access Journals (Sweden)

    Alena Soboleva

    2017-12-01

    Full Text Available Protein glycation is a ubiquitous non-enzymatic post-translational modification, formed by reaction of protein amino and guanidino groups with carbonyl compounds, presumably reducing sugars and α-dicarbonyls. Resulting advanced glycation end products (AGEs represent a highly heterogeneous group of compounds, deleterious in mammals due to their pro-inflammatory effect, and impact in pathogenesis of diabetes mellitus, Alzheimer’s disease and ageing. The body of information on the mechanisms and pathways of AGE formation, acquired during the last decades, clearly indicates a certain site-specificity of glycation. It makes characterization of individual glycation sites a critical pre-requisite for understanding in vivo mechanisms of AGE formation and developing adequate nutritional and therapeutic approaches to reduce it in humans. In this context, proteomics is the methodology of choice to address site-specific molecular changes related to protein glycation. Therefore, here we summarize the methods of Maillard proteomics, specifically focusing on the techniques providing comprehensive structural and quantitative characterization of glycated proteome. Further, we address the novel break-through areas, recently established in the field of Maillard research, i.e., in vitro models based on synthetic peptides, site-based diagnostics of metabolism-related diseases (e.g., diabetes mellitus, proteomics of anti-glycative defense, and dynamics of plant glycated proteome during ageing and response to environmental stress.

  17. Proteomic profiling of triple-negative breast carcinomas in combination with a three-tier orthogonal technology approach identifies Mage-A4 as potential therapeutic target in estrogen receptor negative breast cancer

    DEFF Research Database (Denmark)

    Cabezón, Teresa; Gromova, Irina; Gromov, Pavel

    2013-01-01

    Breast cancer is a very heterogeneous disease, encompassing several intrinsic subtypes with various morphological and molecular features, natural history and response to therapy. Currently, molecular targeted therapies are available for estrogen receptor (ER)(-) and human epidermal growth factor ...

  18. Structural Proteomics of Herpesviruses

    Science.gov (United States)

    Leroy, Baptiste; Gillet, Laurent; Vanderplasschen, Alain; Wattiez, Ruddy

    2016-01-01

    Herpesviruses are highly prevalent viruses associated with numerous pathologies both in animal and human populations. Until now, most of the strategies used to prevent or to cure these infections have been unsuccessful because these viruses have developed numerous immune evasion mechanisms. Therefore, a better understanding of their complex lifecycle is needed. In particular, while the genome of numerous herpesviruses has been sequenced, the exact composition of virions remains unknown for most of them. Mass spectrometry has recently emerged as a central method and has permitted fundamental discoveries in virology. Here, we review mass spectrometry-based approaches that have recently allowed a better understanding of the composition of the herpesvirus virion. In particular, we describe strategies commonly used for proper sample preparation and fractionation to allow protein localization inside the particle but also to avoid contamination by nonstructural proteins. A collection of other important data regarding post-translational modifications or the relative abundance of structural proteins is also described. This review also discusses the poorly studied importance of host proteins in herpesvirus structural proteins and the necessity to develop a quantitative workflow to better understand the dynamics of the structural proteome. In the future, we hope that this collaborative effort will assist in the development of new strategies to fight these infections. PMID:26907323

  19. Proteomics of Eosinophil Activation

    Directory of Open Access Journals (Sweden)

    Deane F. Mosher

    2017-09-01

    Full Text Available We recently identified and quantified >7,000 proteins in non-activated human peripheral blood eosinophils using liquid chromatography coupled to tandem mass spectrometry (LC–MS/MS and described phosphoproteomic changes that accompany acute activation of eosinophils by interleukin-5 (IL5 (1. These data comprise a treasure trove of information about eosinophils. We illustrate the power of label-free LC–MS/MS quantification by considering four examples: complexity of eosinophil STATs, contribution of immunoproteasome subunits to eosinophil proteasomes, complement of integrin subunits, and contribution of platelet proteins originating from platelet–eosinophil complexes to the overall proteome. We describe how isobaric labeling enables robust sample-to-sample comparisons and relate the 220 phosphosites that changed significantly upon treatment with IL5 to previous studies of eosinophil activation. Finally, we review previous attempts to leverage the power of mass spectrometry to discern differences between eosinophils of healthy subjects and those with eosinophil-associated conditions and point out features of label-free quantification and isobaric labeling that are important in planning future mass spectrometric studies.

  20. 2D simulations of hohlraum targets for laser-plasma experiments and ion stopping measurement in hot plasmas

    Energy Technology Data Exchange (ETDEWEB)

    Basko, M.M. [Gesellschaft fuer Schwerionenforschung mbH, Darmstadt (Germany). ExtreMe Matter Institute EMMI; Maruhn, J.; Tauschwitz, Anna [Frankfurt Univ. (Germany); Novikov, V.G.; Grushin, A.S. [Keldysh Institute of Applied Mathematics, Moscow (Russian Federation)

    2011-12-15

    An attractive way to create uniform plasma states at high temperatures and densities is by using hohlraums - cavities with heavy-metal walls that are either directly or indirectly heated by intense laser pulses to x-ray temperatures of tens and hundreds electron volts. A sample material, whose plasma state is to be studied, can be placed inside such a hohlraum (usually in the form of a low-density foam) and uniformly heated to a high temperature. In this case a high-Z hohlraum enclosure serves a double purpose: it prevents the hot plasma from rapid disassembly due to hydrodynamic expansion and, at the same time, suppresses its rapid radiative cooling by providing high diffusive resistivity for X-rays. Of course, both the inertial and the thermal confinement of high-temperature plasmas can be achieved only for a limited period of time - on the order of nanoseconds for millimeter-scale hohlraums. Some time ago such hohlraum targets were proposed for measurements of the stopping power of hot dense plasmas for fast ions at GSI (Darmstadt). Theoretical modeling of hohlraum targets has always been a challenging task for computational physics because it should combine multidimensional hydrodynamic simulations with the solution of the spectral transfer equation for thermal radiation. In this work we report on our latest progress in this direction, namely, we present the results of 2D (two-dimensional) simulations with a newly developed radiation-hydrodynamics code RALEF-2D of two types of the hohlraum targets proposed for experiments on the PHELIX laser at GSI. The first configuration is a simple spherical hohlraum with gold walls and empty interior, which has two holes - one for laser beam entrance, and the other for diagnostics. The hohlraums of this type have already been used in several experimental sessions with the NHELIX and PHELIX lasers at GSI. The second type is a two-chamber cylindrical hohlraum with a characteristic {omega}-shaped cross-section of the enclosure

  1. Detecting differential protein expression in large-scale population proteomics

    Energy Technology Data Exchange (ETDEWEB)

    Ryu, Soyoung; Qian, Weijun; Camp, David G.; Smith, Richard D.; Tompkins, Ronald G.; Davis, Ronald W.; Xiao, Wenzhong

    2014-06-17

    Mass spectrometry-based high-throughput quantitative proteomics shows great potential in clinical biomarker studies, identifying and quantifying thousands of proteins in biological samples. However, methods are needed to appropriately handle issues/challenges unique to mass spectrometry data in order to detect as many biomarker proteins as possible. One issue is that different mass spectrometry experiments generate quite different total numbers of quantified peptides, which can result in more missing peptide abundances in an experiment with a smaller total number of quantified peptides. Another issue is that the quantification of peptides is sometimes absent, especially for less abundant peptides and such missing values contain the information about the peptide abundance. Here, we propose a Significance Analysis for Large-scale Proteomics Studies (SALPS) that handles missing peptide intensity values caused by the two mechanisms mentioned above. Our model has a robust performance in both simulated data and proteomics data from a large clinical study. Because varying patients’ sample qualities and deviating instrument performances are not avoidable for clinical studies performed over the course of several years, we believe that our approach will be useful to analyze large-scale clinical proteomics data.

  2. MASCP Gator: An overview of the Arabidopsis proteomic aggregation portal

    Directory of Open Access Journals (Sweden)

    Gregory W Mann

    2013-10-01

    Full Text Available A key challenge in the area of bioinformatics in the coming decades is the ability to manage the wealth of information that is being generated from the variety of high throughput methodologies currently being undertaken in laboratories across the world. While these approaches have made available large volumes of data to the research community, less attention has been given to the problem of how to intuitively present the data to enable greater biological insights. Recently, an attempt was made to tackle this problem in the area of Arabidopsis proteomics. The model plant has been the target of countless proteomics surveys producing an exhaustive array of data and online repositories. The MASCP Gator is an aggregation portal for proteomic data currently being produced by the community and unites a large collection of specialized resources to a single portal (http://gator.masc-proteomics.org/. Here we describe the latest additions, upgrades and features to this resource further expanding its role into protein modifications and genome sequence variations.

  3. Proteomics for discovery of candidate colorectal cancer biomarkers

    Science.gov (United States)

    Álvarez-Chaver, Paula; Otero-Estévez, Olalla; Páez de la Cadena, María; Rodríguez-Berrocal, Francisco J; Martínez-Zorzano, Vicenta S

    2014-01-01

    Colorectal cancer (CRC) is the second most common cause of cancer-related deaths in Europe and other Western countries, mainly due to the lack of well-validated clinically useful biomarkers with enough sensitivity and specificity to detect this disease at early stages. Although it is well known that the pathogenesis of CRC is a progressive accumulation of mutations in multiple genes, much less is known at the proteome level. Therefore, in the last years many proteomic studies have been conducted to find new candidate protein biomarkers for diagnosis, prognosis and as therapeutic targets for this malignancy, as well as to elucidate the molecular mechanisms of colorectal carcinogenesis. An important advantage of the proteomic approaches is the capacity to look for multiple differentially expressed proteins in a single study. This review provides an overview of the recent reports describing the different proteomic tools used for the discovery of new protein markers for CRC such as two-dimensional electrophoresis methods, quantitative mass spectrometry-based techniques or protein microarrays. Additionally, we will also focus on the diverse biological samples used for CRC biomarker discovery such as tissue, serum and faeces, besides cell lines and murine models, discussing their advantages and disadvantages, and summarize the most frequently identified candidate CRC markers. PMID:24744574

  4. The hemolymph proteome of fed and starved Drosophila larvae.

    Science.gov (United States)

    Handke, Björn; Poernbacher, Ingrid; Goetze, Sandra; Ahrens, Christian H; Omasits, Ulrich; Marty, Florian; Simigdala, Nikiana; Meyer, Imke; Wollscheid, Bernd; Brunner, Erich; Hafen, Ernst; Lehner, Christian F

    2013-01-01

    The co-operation of specialized organ systems in complex multicellular organisms depends on effective chemical communication. Thus, body fluids (like blood, lymph or intraspinal fluid) contain myriads of signaling mediators apart from metabolites. Moreover, these fluids are also of crucial importance for immune and wound responses. Compositional analyses of human body fluids are therefore of paramount diagnostic importance. Further improving their comprehensiveness should increase our understanding of inter-organ communication. In arthropods, which have trachea for gas exchange and an open circulatory system, the single dominating interstitial fluid is the hemolymph. Accordingly, a detailed analysis of hemolymph composition should provide an especially comprehensive picture of chemical communication and defense in animals. Therefore we used an extensive protein fractionation workflow in combination with a discovery-driven proteomic approach to map out the detectable protein composition of hemolymph isolated from Drosophila larvae. Combined mass spectrometric analysis revealed more than 700 proteins extending far beyond the previously known Drosophila hemolymph proteome. Moreover, by comparing hemolymph isolated from either fed or starved larvae, we provide initial provisional insights concerning compositional changes in response to nutritional state. Storage proteins in particular were observed to be strongly reduced by starvation. Our hemolymph proteome catalog provides a rich basis for data mining, as exemplified by our identification of potential novel cytokines, as well as for future quantitative analyses by targeted proteomics.

  5. The hemolymph proteome of fed and starved Drosophila larvae.

    Directory of Open Access Journals (Sweden)

    Björn Handke

    Full Text Available The co-operation of specialized organ systems in complex multicellular organisms depends on effective chemical communication. Thus, body fluids (like blood, lymph or intraspinal fluid contain myriads of signaling mediators apart from metabolites. Moreover, these fluids are also of crucial importance for immune and wound responses. Compositional analyses of human body fluids are therefore of paramount diagnostic importance. Further improving their comprehensiveness should increase our understanding of inter-organ communication. In arthropods, which have trachea for gas exchange and an open circulatory system, the single dominating interstitial fluid is the hemolymph. Accordingly, a detailed analysis of hemolymph composition should provide an especially comprehensive picture of chemical communication and defense in animals. Therefore we used an extensive protein fractionation workflow in combination with a discovery-driven proteomic approach to map out the detectable protein composition of hemolymph isolated from Drosophila larvae. Combined mass spectrometric analysis revealed more than 700 proteins extending far beyond the previously known Drosophila hemolymph proteome. Moreover, by comparing hemolymph isolated from either fed or starved larvae, we provide initial provisional insights concerning compositional changes in response to nutritional state. Storage proteins in particular were observed to be strongly reduced by starvation. Our hemolymph proteome catalog provides a rich basis for data mining, as exemplified by our identification of potential novel cytokines, as well as for future quantitative analyses by targeted proteomics.

  6. Analysis of proteomic changes of the serum of irradiated mice

    International Nuclear Information System (INIS)

    Wang Zhidong; Chen Xiaohua; Dong Bo; Zhang Junquan; Rao Yalan; Gao Ronglian; Hou Lili; Mao Bingzhi

    2005-01-01

    To explore the early diagnostic factors, new therapeutic targets and mechanisms of acute radiation disease. Proteomic changes of the serum of irradiated mice were studied using 2-DE and Q-TOF-MS approaches. One higher level expressed protein after the irradiation was found, and it was identified as α chain of haptoglobin by Q-TOF-MS. The authors confirmed the result by Western blotting with anti-haptoglobin antibody. Haptoglobin may involve in the process of acute radiation injury. (authors)

  7. Target gene expression levels and competition between transfected and endogenous microRNAs are strong confounding factors in microRNA high-throughput experiments

    Science.gov (United States)

    2012-01-01

    Background MicroRNA (miRNA) target genes tend to have relatively long and conserved 3' untranslated regions (UTRs), but to what degree these characteristics contribute to miRNA targeting is poorly understood. Different high-throughput experiments have, for example, shown that miRNAs preferentially regulate genes with both short and long 3' UTRs and that target site conservation is both important and irrelevant for miRNA targeting. Results We have analyzed several gene context-dependent features, including 3' UTR length, 3' UTR conservation, and messenger RNA (mRNA) expression levels, reported to have conflicting influence on miRNA regulation. By taking into account confounding factors such as technology-dependent experimental bias and competition between transfected and endogenous miRNAs, we show that two factors - target gene expression and competition - could explain most of the previously reported experimental differences. Moreover, we find that these and other target site-independent features explain about the same amount of variation in target gene expression as the target site-dependent features included in the TargetScan model. Conclusions Our results show that it is important to consider confounding factors when interpreting miRNA high throughput experiments and urge special caution when using microarray data to compare average regulatory effects between groups of genes that have different average gene expression levels. PMID:22325809

  8. Radiotherapy for Brain Metastases From Renal Cell Carcinoma in the Targeted Therapy Era: The University of Rochester Experience.

    Science.gov (United States)

    Bates, James E; Youn, Paul; Peterson, Carl R; Usuki, Kenneth Y; Walter, Kevin A; Okunieff, Paul; Milano, Michael T

    2017-10-01

    Radiotherapy remains the standard approach for brain metastases from renal cell carcinoma (RCC). Kinase inhibitors (KI) have become standard of care for metastatic RCC. They also increase the radiosensitivity of various tumor types in preclinical models. Data are lacking regarding the effect of KIs among RCC patients undergoing radiotherapy for brain metastases. We report our experience of radiotherapy for brain metastatic RCC in the era of targeted therapy and analyzed effects of concurrent KI therapy. We retrospectively analyzed 25 consecutive patients who received radiotherapy for brain metastases from RCC with whole-brain radiotherapy (WBRT), stereotactic radiosurgery (SRS), or both. Kaplan-Meier rates of overall survival (OS) and brain progression-free survival (BPFS) were calculated and univariate analyses performed. Lower diagnosis-specific graded prognostic assessment (DS-GPA) score and multiple intracranial metastases were associated with decreased OS and BPFS on univariate analysis; DS-GPA is also a prognostic factor on multivariate analysis. There was no significant difference in OS or BPFS for SRS compared with WBRT or WBRT and SRS combined. The concurrent use of KI was not associated with any change in OS or BPFS. This hypothesis-generating analysis suggests among patients with brain metastatic RCC treated with the most current therapies, those selected to undergo SRS did not experience significantly different survival or control outcomes than those selected to undergo WBRT. From our experience to date, limited in patient numbers, there seems to be neither harm nor benefit in using concurrent KI therapy during radiotherapy. Given that most patients progress systemically, we would recommend considering KI use during brain radiotherapy in these patients.

  9. The Seed Proteome Web Portal

    Directory of Open Access Journals (Sweden)

    Marc eGalland

    2012-06-01

    Full Text Available The Seed Proteome Web Portal (SPWP; http://www.seedproteome.com/ gives access to information both on quantitative seed proteomic data and on seed-related protocols. Firstly, the SPWP provides access to the 475 different Arabidopsis seed proteins annotated from 2 dimensional electrophoresis (2DE maps. Quantitative data are available for each protein according to their accumulation profile during the germination process. These proteins can be retrieved either in list format or directly on scanned 2DE maps. These proteomic data reveal that 40% of seed proteins maintain a stable abundance over germination, up to radicle protrusion. During sensu stricto germination (24 h upon imbibition about 50% of the proteins display quantitative variations, exhibiting an increased abundance (35% or a decreasing abundance (15%. Moreover, during radicle protrusion (24 h to 48 h upon imbibition, 41% proteins display quantitative variations with an increased (23% or a decreasing abundance (18%. In addition, an analysis of the seed proteome revealed the importance of protein post-translational modifications as demonstrated by the poor correlation (r2 = 0.29 between the theoretical (predicted from Arabidopsis genome and the observed protein isoelectric points. Secondly, the SPWP is a relevant technical resource for protocols specifically dedicated to Arabidopsis seed proteome studies. Concerning 2D electrophoresis, the user can find efficient procedures for sample preparation, electrophoresis coupled with gel analysis and protein identification by mass spectrometry, which we have routinely used during the last 12 years. Particular applications such as the detection of oxidized proteins or de novo synthetized proteins radiolabeled by [35S]-methionine are also given in great details. Future developments of this portal will include proteomic data from studies such as dormancy release and protein turnover through de novo protein synthesis analyses during germination.

  10. Advances of Proteomic Sciences in Dentistry.

    Science.gov (United States)

    Khurshid, Zohaib; Zohaib, Sana; Najeeb, Shariq; Zafar, Muhammad Sohail; Rehman, Rabia; Rehman, Ihtesham Ur

    2016-05-13

    Applications of proteomics tools revolutionized various biomedical disciplines such as genetics, molecular biology, medicine, and dentistry. The aim of this review is to highlight the major milestones in proteomics in dentistry during the last fifteen years. Human oral cavity contains hard and soft tissues and various biofluids including saliva and crevicular fluid. Proteomics has brought revolution in dentistry by helping in the early diagnosis of various diseases identified by the detection of numerous biomarkers present in the oral fluids. This paper covers the role of proteomics tools for the analysis of oral tissues. In addition, dental materials proteomics and their future directions are discussed.

  11. Proteomic classification of breast cancer.

    LENUS (Irish Health Repository)

    Kamel, Dalia

    2012-11-01

    Being a significant health problem that affects patients in various age groups, breast cancer has been extensively studied to date. Recently, molecular breast cancer classification has advanced significantly with the availability of genomic profiling technologies. Proteomic technologies have also advanced from traditional protein assays including enzyme-linked immunosorbent assay, immunoblotting and immunohistochemistry to more comprehensive approaches including mass spectrometry and reverse phase protein lysate arrays (RPPA). The purpose of this manuscript is to review the current protein markers that influence breast cancer prediction and prognosis and to focus on novel advances in proteomic classification of breast cancer.

  12. Scientific Workflow Management in Proteomics

    Science.gov (United States)

    de Bruin, Jeroen S.; Deelder, André M.; Palmblad, Magnus

    2012-01-01

    Data processing in proteomics can be a challenging endeavor, requiring extensive knowledge of many different software packages, all with different algorithms, data format requirements, and user interfaces. In this article we describe the integration of a number of existing programs and tools in Taverna Workbench, a scientific workflow manager currently being developed in the bioinformatics community. We demonstrate how a workflow manager provides a single, visually clear and intuitive interface to complex data analysis tasks in proteomics, from raw mass spectrometry data to protein identifications and beyond. PMID:22411703

  13. Proteome analysis of ofloxacin and moxifloxacin induced mycobacterium tuberculosis isolates by proteomic approach.

    Science.gov (United States)

    Lata, Manju; Sharma, Divakar; Kumar, Bhavnesh; Deo, Nirmala; Tiwari, Pramod Kumar; Bisht, Deepa; Venkatesan, Krishnamurthy

    2015-01-01

    Ofloxacin (OFX) and moxifloxacin (MOX) are the most promising second line drugs for tuberculosis treatment. Although the primary mechanism of action of OFX and MOX is gyrase inhibition, other possible mechanisms cannot be ruled out. Being the functional moiety of cell, the proteins act as primary targets for developing drugs, diagnostics and therapeutics. In this study we have investigated the proteomic changes of Mycobacterium tuberculosis isolates induced by OFX and MOX by applying comparative proteomic approaches based on two-dinensional gel electrophoresis (2DE) along with matrix assisted laser desorption ionisation time of flight mass spectrometry (MALDI TOF/TOF-MS) and bioinformatic tools. The findings are likely to provide new understanding of OFX and MOX mechanisms that might be helpful in exploring new diagnostics and drug targets. Our study explored eleven proteins (Rv2889c, Rv2623, Rv0952, Rv1827, Rv1932, Rv0054, Rv1080c, Rv3418c, Rv3914, Rv1636 and Rv0009) that were overexpressed in the presence of drugs. Among them, Rv2623, Rv1827 and Rv1636 were identified as proteins with unknown function. InterProScan and molecular docking revealed that the conserved domain of hypothetical proteins interact with OFX and MOX which indicate a probable inhibition/modulation of the functioning of these proteins by both drugs, which might be overexpressed to overcome this effect.

  14. Statistics in experimental design, preprocessing, and analysis of proteomics data.

    Science.gov (United States)

    Jung, Klaus

    2011-01-01

    High-throughput experiments in proteomics, such as 2-dimensional gel electrophoresis (2-DE) and mass spectrometry (MS), yield usually high-dimensional data sets of expression values for hundreds or thousands of proteins which are, however, observed on only a relatively small number of biological samples. Statistical methods for the planning and analysis of experiments are important to avoid false conclusions and to receive tenable results. In this chapter, the most frequent experimental designs for proteomics experiments are illustrated. In particular, focus is put on studies for the detection of differentially regulated proteins. Furthermore, issues of sample size planning, statistical analysis of expression levels as well as methods for data preprocessing are covered.

  15. Infectious Disease Proteome Biomarkers: Final Technical Report

    Energy Technology Data Exchange (ETDEWEB)

    Bailey, Charles L.

    2011-12-31

    Research for the DOE Infectious Disease Proteome Biomarkers focused on Rift Valley fever virus (RVFV) and Venezuelan Equine Encephalitis Virus (VEEV). RVFV and VEEV are Category A and B pathogens respectively. Among the priority threats, RVFV and VEEV rank high in their potential for being weaponized and introduced to the United States, spreading quickly, and having a large health and economic impact. In addition, they both have live attenuated vaccine, which allows work to be performed at BSL-2. While the molecular biology of RVFV and VEEV are increasingly well-characterized, little is known about its host-pathogen interactions. Our research is aimed at determining critical alterations in host signaling pathways to identify therapeutics targeted against the host.