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Sample records for based phosphoproteomic analysis

  1. Phosphoproteomics-based systems analysis of signal transduction networks

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    Hiroko eKozuka-Hata

    2012-01-01

    Full Text Available Signal transduction systems coordinate complex cellular information to regulate biological events such as cell proliferation and differentiation. Although the accumulating evidence on widespread association of signaling molecules has revealed essential contribution of phosphorylation-dependent interaction networks to cellular regulation, their dynamic behavior is mostly yet to be analyzed. Recent technological advances regarding mass spectrometry-based quantitative proteomics have enabled us to describe the comprehensive status of phosphorylated molecules in a time-resolved manner. Computational analyses based on the phosphoproteome dynamics accelerate generation of novel methodologies for mathematical analysis of cellular signaling. Phosphoproteomics-based numerical modeling can be used to evaluate regulatory network elements from a statistical point of view. Integration with transcriptome dynamics also uncovers regulatory hubs at the transcriptional level. These omics-based computational methodologies, which have firstly been applied to representative signaling systems such as the epidermal growth factor receptor pathway, have now opened up a gate for systems analysis of signaling networks involved in immune response and cancer.

  2. Quantitative phosphoproteomic analysis of postmortem muscle development

    DEFF Research Database (Denmark)

    Huang, Honggang

    )-based quantitative phosphoproteomic strategies were employed to analyze PM muscle with the aim to intensively characterize the protein phosphorylation involved in meat quality development. Firstly, gel-based phosphoproteomic studies were performed to analyze the protein phosphorylation in both sarcoplasmic proteins...... proteins in beef. The majority of the identified phosphoproteins were glycometabolism related enzymes in the sarcoplasmic fraction and contraction related proteins in the myofibrillar fraction. Subsequently, the quantitative LC-MS/MS-based phosphoproteomic strategy was used to identify and quantify...

  3. Phosphotyrosine-based-phosphoproteomics scaled-down to biopsy level for analysis of individual tumor biology and treatment selection.

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    Labots, Mariette; van der Mijn, Johannes C; Beekhof, Robin; Piersma, Sander R; de Goeij-de Haas, Richard R; Pham, Thang V; Knol, Jaco C; Dekker, Henk; van Grieken, Nicole C T; Verheul, Henk M W; Jiménez, Connie R

    2017-06-06

    Mass spectrometry-based phosphoproteomics of cancer cell and tissue lysates provides insight in aberrantly activated signaling pathways and potential drug targets. For improved understanding of individual patient's tumor biology and to allow selection of tyrosine kinase inhibitors in individual patients, phosphoproteomics of small clinical samples should be feasible and reproducible. We aimed to scale down a pTyr-phosphopeptide enrichment protocol to biopsy-level protein input and assess reproducibility and applicability to tumor needle biopsies. To this end, phosphopeptide immunoprecipitation using anti-phosphotyrosine beads was performed using 10, 5 and 1mg protein input from lysates of colorectal cancer (CRC) cell line HCT116. Multiple needle biopsies from 7 human CRC resection specimens were analyzed at the 1mg-level. The total number of phosphopeptides captured and detected by LC-MS/MS ranged from 681 at 10mg input to 471 at 1mg HCT116 protein. ID-reproducibility ranged from 60.5% at 10mg to 43.9% at 1mg. Per 1mg-level biopsy sample, >200 phosphopeptides were identified with 57% ID-reproducibility between paired tumor biopsies. Unsupervised analysis clustered biopsies from individual patients together and revealed known and potential therapeutic targets. This study demonstrates the feasibility of label-free pTyr-phosphoproteomics at the tumor biopsy level based on reproducible analyses using 1mg of protein input. The considerable number of identified phosphopeptides at this level is attributed to an effective down-scaled immuno-affinity protocol as well as to the application of ID propagation in the data processing and analysis steps. Unsupervised cluster analysis reveals patient-specific profiles. Together, these findings pave the way for clinical trials in which pTyr-phosphoproteomics will be performed on pre- and on-treatment biopsies. Such studies will improve our understanding of individual tumor biology and may enable future pTyr-phosphoproteomics-based

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

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

    2016-08-22

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

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

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    Maria Hernandez-Valladares

    2016-08-01

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

  6. SILAC-Based Temporal Phosphoproteomics

    DEFF Research Database (Denmark)

    Francavilla, Chiara; Hekmat, Omid; Blagoev, Blagoy

    2014-01-01

    In recent years, thanks to advances in Mass Spectrometry (MS)-based quantitative proteomics, studies on signaling pathways have moved from a detailed description of individual components to system-wide analysis of entire signaling cascades, also providing spatio-temporal views of intracellular...... pathways. Quantitative proteomics that combines stable isotope labeling by amino acid in cell culture (SILAC) with enrichment strategies for post-translational modification-bearing peptides and high-performance tandem mass spectrometry represents a powerful and unbiased approach to monitor dynamic...

  7. Assessment of phosphopeptide enrichment/precipitation method for LC-MS/MS based phosphoproteomic analysis of plant tissue

    DEFF Research Database (Denmark)

    Ye, Juanying; Rudashevskaya, Elena; Hansen, Thomas Aarup

    selectivity. The overlap between the 3 enrichment experiments was quite small. We are currently investigating further combination of enrichment methods: SIMAC enrichment and the combination of CPP and IMAC enrichment. Samples will be analyzed by LTQ-Orbitrap-ETD MS, and the behavior of phosphopeptides on CID...... is necessary. At present, numerous phosphopeptide enrichment approaches have been established and applied to complex biological samples. We and others have reported that multi-step phosphopeptide purification methods enable better recovery of phosphopeptide and achieve higher selectivity and sensitivity than...... stardand sample preparation protocols. Here, we combine 3 phosphpeptide enrichment methods (IMAC, TiO2 and Calcium Phosphate Precipitation (CPP)), and apply them to phosphoproteomic analysis of Arabidopsis thaliana plasma membrane preparation. Method Plant plasma membranes were isolated from Arabidopsis...

  8. Interleukin-2 signaling pathway analysis by quantitative phosphoproteomics

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    Osinalde, Nerea; Moss, Helle; Arrizabalaga, Onetsine

    2011-01-01

    among which 79 were found with increased abundance in the tyrosine-phosphorylated complexes, including several previously not reported IL-2 downstream effectors. Combinatorial site-specific phosphoproteomic analysis resulted in identification of 99 phosphorylated sites mapping to the identified proteins...

  9. Dataset of the Botrytis cinerea phosphoproteome induced by different plant-based elicitors

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    Eva Liñeiro

    2016-06-01

    Full Text Available Phosphorylation is one of the main post-translational modification (PTM involved in signaling network in the ascomycete Botrytis cinerea, one of the most relevant phytopathogenic fungus. The data presented in this article provided a differential mass spectrometry-based analysis of the phosphoproteome of B. cinerea under two different phenotypical conditions induced by the use of two different elicitors: glucose and deproteinized Tomate Cell Walls (TCW. A total 1138 and 733 phosphoproteins were identified for glucose and TCW culture conditions respectively. Raw data are deposited at the ProteomeXchange Consortium via the PRIDE partner repository with the data set identifier (PRIDE: http://www.ebi.ac.uk/pride/archive/projects/PXD003099. Further interpretation and discussion of these data are provided in our research article entitled “Phosphoproteome analysis of B.cinerea in response to different plant-based elicitors” (Liñeiro et al., 2016 [1].

  10. Dataset of the Botrytis cinerea phosphoproteome induced by different plant-based elicitors.

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    Liñeiro, Eva; Chiva, Cristina; Cantoral, Jesús M; Sabido, Eduard; Fernández-Acero, Francisco Javier

    2016-06-01

    Phosphorylation is one of the main post-translational modification (PTM) involved in signaling network in the ascomycete Botrytis cinerea , one of the most relevant phytopathogenic fungus. The data presented in this article provided a differential mass spectrometry-based analysis of the phosphoproteome of B. cinerea under two different phenotypical conditions induced by the use of two different elicitors: glucose and deproteinized Tomate Cell Walls (TCW). A total 1138 and 733 phosphoproteins were identified for glucose and TCW culture conditions respectively. Raw data are deposited at the ProteomeXchange Consortium via the PRIDE partner repository with the data set identifier (PRIDE: http://www.ebi.ac.uk/pride/archive/projects/PXD003099). Further interpretation and discussion of these data are provided in our research article entitled "Phosphoproteome analysis of B.cinerea in response to different plant-based elicitors" (Liñeiro et al., 2016) [1].

  11. Dataset of the Botrytis cinerea phosphoproteome induced by different plant-based elicitors

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    Eva Liñeiro; Cristina Chiva; Jesús M. Cantoral; Eduard Sabido; Francisco Javier Fernández-Acero

    2016-01-01

    Phosphorylation is one of the main post-translational modification (PTM) involved in signaling network in the ascomycete Botrytis cinerea, one of the most relevant phytopathogenic fungus. The data presented in this article provided a differential mass spectrometry-based analysis of the phosphoproteome of B. cinerea under two different phenotypical conditions induced by the use of two different elicitors: glucose and deproteinized Tomate Cell Walls (TCW). A total 1138 and 733 phosphoproteins w...

  12. Phosphoproteomics analysis of a clinical Mycobacterium tuberculosis Beijing isolate: expanding the mycobacterial phosphoproteome catalog.

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    Fortuin, Suereta; Tomazella, Gisele G; Nagaraj, Nagarjuna; Sampson, Samantha L; Gey van Pittius, Nicolaas C; Soares, Nelson C; Wiker, Harald G; de Souza, Gustavo A; Warren, Robin M

    2015-01-01

    Reversible protein phosphorylation, regulated by protein kinases and phosphatases, mediates a switch between protein activity and cellular pathways that contribute to a large number of cellular processes. The Mycobacterium tuberculosis genome encodes 11 Serine/Threonine kinases (STPKs) which show close homology to eukaryotic kinases. This study aimed to elucidate the phosphoproteomic landscape of a clinical isolate of M. tuberculosis. We performed a high throughput mass spectrometric analysis of proteins extracted from an early-logarithmic phase culture. Whole cell lysate proteins were processed using the filter-aided sample preparation method, followed by phosphopeptide enrichment of tryptic peptides by strong cation exchange (SCX) and Titanium dioxide (TiO2) chromatography. The MaxQuant quantitative proteomics software package was used for protein identification. Our analysis identified 414 serine/threonine/tyrosine phosphorylated sites, with a distribution of S/T/Y sites; 38% on serine, 59% on threonine and 3% on tyrosine; present on 303 unique peptides mapping to 214 M. tuberculosis proteins. Only 45 of the S/T/Y phosphorylated proteins identified in our study had been previously described in the laboratory strain H37Rv, confirming previous reports. The remaining 169 phosphorylated proteins were newly identified in this clinical M. tuberculosis Beijing strain. We identified 5 novel tyrosine phosphorylated proteins. These findings not only expand upon our current understanding of the protein phosphorylation network in clinical M. tuberculosis but the data set also further extends and complements previous knowledge regarding phosphorylated peptides and phosphorylation sites in M. tuberculosis.

  13. Quantitative Phosphoproteomics Analysis of ERBB3/ERBB4 Signaling.

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    Sebastian K Wandinger

    Full Text Available The four members of the epidermal growth factor receptor (EGFR/ERBB family form homo- and heterodimers which mediate ligand-specific regulation of many key cellular processes in normal and cancer tissues. While signaling through the EGFR has been extensively studied on the molecular level, signal transduction through ERBB3/ERBB4 heterodimers is less well understood. Here, we generated isogenic mouse Ba/F3 cells that express full-length and functional membrane-integrated ERBB3 and ERBB4 or ERBB4 alone, to serve as a defined cellular model for biological and phosphoproteomics analysis of ERBB3/ERBB4 signaling. ERBB3 co-expression significantly enhanced Ba/F3 cell proliferation upon neuregulin-1 (NRG1 treatment. For comprehensive signaling studies we performed quantitative mass spectrometry (MS experiments to compare the basal ERBB3/ERBB4 cell phosphoproteome to NRG1 treatment of ERBB3/ERBB4 and ERBB4 cells. We employed a workflow comprising differential isotope labeling with mTRAQ reagents followed by chromatographic peptide separation and final phosphopeptide enrichment prior to MS analysis. Overall, we identified 9686 phosphorylation sites which could be confidently localized to specific residues. Statistical analysis of three replicate experiments revealed 492 phosphorylation sites which were significantly changed in NRG1-treated ERBB3/ERBB4 cells. Bioinformatics data analysis recapitulated regulation of mitogen-activated protein kinase and Akt pathways, but also indicated signaling links to cytoskeletal functions and nuclear biology. Comparative assessment of NRG1-stimulated ERBB4 Ba/F3 cells revealed that ERBB3 did not trigger defined signaling pathways but more broadly enhanced phosphoproteome regulation in cells expressing both receptors. In conclusion, our data provide the first global picture of ERBB3/ERBB4 signaling and provide numerous potential starting points for further mechanistic studies.

  14. Phosphoproteomics-based modeling defines the regulatory mechanism underlying aberrant EGFR signaling.

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    Shinya Tasaki

    Full Text Available BACKGROUND: Mutation of the epidermal growth factor receptor (EGFR results in a discordant cell signaling, leading to the development of various diseases. However, the mechanism underlying the alteration of downstream signaling due to such mutation has not yet been completely understood at the system level. Here, we report a phosphoproteomics-based methodology for characterizing the regulatory mechanism underlying aberrant EGFR signaling using computational network modeling. METHODOLOGY/PRINCIPAL FINDINGS: Our phosphoproteomic analysis of the mutation at tyrosine 992 (Y992, one of the multifunctional docking sites of EGFR, revealed network-wide effects of the mutation on EGF signaling in a time-resolved manner. Computational modeling based on the temporal activation profiles enabled us to not only rediscover already-known protein interactions with Y992 and internalization property of mutated EGFR but also further gain model-driven insights into the effect of cellular content and the regulation of EGFR degradation. Our kinetic model also suggested critical reactions facilitating the reconstruction of the diverse effects of the mutation on phosphoproteome dynamics. CONCLUSIONS/SIGNIFICANCE: Our integrative approach provided a mechanistic description of the disorders of mutated EGFR signaling networks, which could facilitate the development of a systematic strategy toward controlling disease-related cell signaling.

  15. Gel-based phosphoproteomics analysis of sarcoplasmic proteins in postmortem porcine muscle with pH decline rate and time differences

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    Huang, Honggang; Larsen, Martin Røssel; Karlsson, Anders H

    2011-01-01

    Meat quality development is highly influenced by the pH decline caused by the postmortem (PM) glycolysis. Protein phosphorylation is an important mechanism in regulating the activity of glycometabolic enzymes. Here, a gel-based phosphoproteomic study was performed to analyze the protein...... observed in most individual bands in 1-DE. The protein phosphorylation levels of 12 bands were significantly affected by the synergy effects of pH and time (p...... phosphorylation in sarcoplasmic proteins from three groups of pigs with different pH decline rates from PM 1 to 24¿h. Globally, the fast pH decline group had the highest phosphorylation level at PM 1¿h, but lowest at 24¿h, whereas the slow pH decline group showed the reverse case. The same pattern was also...

  16. Quantitative Proteomic and Phosphoproteomic Analysis of Trypanosoma cruzi Amastigogenesis

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    Queiroz, Rayner M L; Charneau, Sebastien; Mandacaru, Samuel C

    2014-01-01

    this well-established differentiation protocol to perform a comprehensive quantitative proteomic and phosphoproteomic analysis of the T. cruzi amastigogenesis. Samples from fully differentiated forms and two biologically relevant intermediate time points were Lys-C/trypsin digested, i......TRAQ-labeled and multiplexed. Subsequently, phosphopeptides were enriched using TiO2 matrix. Non-phosphorylated peptides were HILIC-fractionated prior to LC-MS/MS analysis. LC-MS/MS and bioinformatics procedures were used for protein and phosphopeptide quantitation, identification and phosphorylation site assignment. We could...... induced by incubation in acidic medium were also evinced. To our knowledge, this work is the most comprehensive quantitative proteomics study of the T. cruzi amastigogenesis and this data will provide trustworthy basis for future studies and possibly for new potential drug targets....

  17. Quantitative phosphoproteomic analysis of porcine muscle within 24 h postmortem

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    Huang, Honggang; Larsen, Martin Røssel; Palmisano, Giuseppe

    2014-01-01

    UNLABELLED: Protein phosphorylation can regulate most of the important processes in muscle, such as metabolism and contraction. The postmortem (PM) metabolism and rigor mortis have essential effects on meat quality. In order to identify and characterize the protein phosphorylation events involved...... in meat quality development, a quantitative mass spectrometry-based phosphoproteomic study was performed to analyze the porcine muscle within 24h PM using dimethyl labeling combined with the TiSH phosphopeptide enrichment strategy. In total 305 unique proteins were identified, including 160...... phosphoproteins with 784 phosphorylation sites. Among these, 184 phosphorylation sites on 93 proteins had their phosphorylation levels significantly changed. The proteins involved in glucose metabolism and muscle contraction were the two largest clusters of phosphoproteins with significantly changed...

  18. In Vivo SILAC-Based Proteomics Reveals Phosphoproteome Changes during Mouse Skin Carcinogenesis

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    Sara Zanivan

    2013-02-01

    Full Text Available Cancer progresses through distinct stages, and mouse models recapitulating traits of this progression are frequently used to explore genetic, morphological, and pharmacological aspects of tumor development. To complement genomic investigations of this process, we here quantify phosphoproteomic changes in skin cancer development using the SILAC mouse technology coupled to high-resolution mass spectrometry. We distill protein expression signatures from our data that distinguish between skin cancer stages. A distinct phosphoproteome of the two stages of cancer progression is identified that correlates with perturbed cell growth and implicates cell adhesion as a major driver of malignancy. Importantly, integrated analysis of phosphoproteomic data and prediction of kinase activity revealed PAK4-PKC/SRC network to be highly deregulated in SCC but not in papilloma. This detailed molecular picture, both at the proteome and phosphoproteome level, will prove useful for the study of mechanisms of tumor progression.

  19. Phosphoproteomics analysis of postmortem porcine muscle with pH decline rate and time difference

    DEFF Research Database (Denmark)

    Huang, Honggang; Larsen, Martin R; Karlsson, Anders H

    2012-01-01

    The aim of this study was to characterize the protein phosphorylation in postmortem (PM) muscle and reveal the change during meat quality development. The gel-based phosphoproteomic analysis of PM porcine muscle was performed in three pig groups with different pH decline rates from PM 1h to 24 h....... The sarcoplasmic and myofibrillar fractions were analyzed using gel electrophoresis in combination with a phosphoprotein specific staining. Globally, the group with fast pH decline rate had the highest phosphorylation level at PM 1 h, but lowest at PM 24 h, whereas the group with slow pH decline rate showed...

  20. Identifying Novel Signaling Pathways: An Exercise Scientists Guide to Phosphoproteomics.

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    Wilson, Gary M; Blanco, Rocky; Coon, Joshua J; Hornberger, Troy A

    2018-01-15

    We propose that phosphoproteomic-based studies will radically advance our knowledge about exercise regulated signaling events. However, these studies utilize cutting-edge technologies that can be difficult for non-specialists to understand. Hence, this review is intended to help non-specialists: 1) understand the fundamental technologies behind phosphoproteomic analysis and 2) employ various bioinformatic tools that can be used to interrogate phosphoproteomic datasets.

  1. Quantitative phosphoproteomics to characterize signaling networks

    DEFF Research Database (Denmark)

    Rigbolt, Kristoffer T G; Blagoev, Blagoy

    2012-01-01

    for analyzing protein phosphorylation at a system-wide scale and has become the intuitive strategy for comprehensive characterization of signaling networks. Contemporary phosphoproteomics use highly optimized procedures for sample preparation, mass spectrometry and data analysis algorithms to identify...... in phosphoproteomics technology that have facilitated the application of phosphoproteomics to signaling networks and introduce examples of recent system-wide applications of quantitative phosphoproteomics. Despite the great advances in phosphoproteomics technology there are still several outstanding issues and we...

  2. Kinomic and phospho-proteomic analysis of breast cancer stem-like cells

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    Leth-Larsen, Rikke; Christensen, Anne Geske Lindhard; Ehmsen, Sidse

    Kinomic and phospho-proteomic analysis of breast cancer stem-like cells Rikke Leth-Larsen1, Anne G Christensen1, Sidse Ehmsen1, Mark Møller1, Giuseppe Palmisano2, Martin R Larsen2, Henrik J Ditzel1,3 1Institute of Molecular Medicine, University of Southern Denmark, Odense, Denmark 2Institute...

  3. Multidimensional electrostatic repulsion-hydrophilic interaction chromatography (ERLIC) for quantitative analysis of the proteome and phosphoproteome in clinical and biomedical research.

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    Loroch, Stefan; Schommartz, Tim; Brune, Wolfram; Zahedi, René Peiman; Sickmann, Albert

    2015-05-01

    Quantitative proteomics and phosphoproteomics have become key disciplines in understanding cellular processes. Fundamental research can be done using cell culture providing researchers with virtually infinite sample amounts. In contrast, clinical, pre-clinical and biomedical research is often restricted to minute sample amounts and requires an efficient analysis with only micrograms of protein. To address this issue, we generated a highly sensitive workflow for combined LC-MS-based quantitative proteomics and phosphoproteomics by refining an ERLIC-based 2D phosphoproteomics workflow into an ERLIC-based 3D workflow covering the global proteome as well. The resulting 3D strategy was successfully used for an in-depth quantitative analysis of both, the proteome and the phosphoproteome of murine cytomegalovirus-infected mouse fibroblasts, a model system for host cell manipulation by a virus. In a 2-plex SILAC experiment with 150 μg of a tryptic digest per condition, the 3D strategy enabled the quantification of ~75% more proteins and even ~134% more peptides compared to the 2D strategy. Additionally, we could quantify ~50% more phosphoproteins by non-phosphorylated peptides, concurrently yielding insights into changes on the levels of protein expression and phosphorylation. Beside its sensitivity, our novel three-dimensional ERLIC-strategy has the potential for semi-automated sample processing rendering it a suitable future perspective for clinical, pre-clinical and biomedical research. Copyright © 2015. Published by Elsevier B.V.

  4. Global analysis of neuronal phosphoproteome regulation by chondroitin sulfate proteoglycans.

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    Panpan Yu

    Full Text Available Chondroitin sulfate proteoglycans (CSPGs are major components of the extracellular matrix which mediate inhibition of axonal regeneration after injury to the central nervous system (CNS. Several neuronal receptors for CSPGs have recently been identified; however, the signaling pathways by which CSPGs restrict axonal growth are still largely unknown. In this study, we applied quantitative phosphoproteomics to investigate the global changes in protein phosphorylation induced by CSPGs in primary neurons. In combination with isobaric Tags for Relative and Absolute Quantitation (iTRAQ labeling, strong cation exchange chromatography (SCX fractionation, immobilized metal affinity chromatography (IMAC and LC-MS/MS, we identified and quantified 2214 unique phosphopeptides corresponding to 1118 phosphoproteins, with 118 changing significantly in abundance with CSPG treatment. The proteins that were regulated by CSPGs included key components of synaptic vesicle trafficking, axon guidance mediated by semaphorins, integrin signaling, cadherin signaling and EGF receptor signaling pathways. A significant number of the regulated proteins are cytoskeletal and related proteins that have been implicated in regulating neurite growth. Another highly represented protein category regulated by CSPGs is nucleic acid binding proteins involved in RNA post-transcriptional regulation. Together, by screening the overall phosphoproteome changes induced by CSPGs, this data expand our understanding of CSPG signaling, which provides new insights into development of strategies for overcoming CSPG inhibition and promoting axonal regeneration after CNS injury.

  5. Phosphoproteomic analysis of the resistant and susceptible genotypes of maize infected with sugarcane mosaic virus.

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    Wu, Liuji; Wang, Shunxi; Wu, Jianyu; Han, Zanping; Wang, Rui; Wu, Liancheng; Zhang, Huimin; Chen, Yanhui; Hu, Xiuli

    2015-03-01

    Protein phosphorylation plays a pivotal role in the regulation of many cellular events. No information is yet available, however, on protein phosphorylation in plants in response to virus infection. In this study, we characterized phosphoproteomes of resistant and susceptible genotypes of maize (Zea mays L.) in response to Sugarcane mosaic virus (SCMV) infection. Based on isotope tags for relative and absolute quantification technology, TiO2 enrichment method and LC-MS/MS analysis, we identified 65 and 59 phosphoproteins respectively, whose phosphorylation level regulated significantly in susceptible and resistant plants. Some identified phosphoproteins were shared by both genotypes, suggesting a partial overlapping of the responsive pathways to virus infection. While several phosphoproteins are well-known pathogen response phosphoproteins, virus infection differentially regulates most other phosphoproteins, which has not been reported in literature. Changes in protein phosphorylation status indicated that response to SCMV infection encompass a reformatting of major cellular processes. Our data provide new valuable insights into plant-virus interactions.

  6. Phosphoproteome analysis of functional mitochondria isolated from resting human muscle reveals extensive phosphorylation of inner membrane protein complexes and enzymes

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    Zhao, Xiaolu; Leon, Ileana R; Bak, Steffen

    2011-01-01

    . In skeletal muscle, mitochondrial dysfunction is linked to insulin resistance in humans with obesity and type 2 diabetes. We performed a phosphoproteomic study of functional mitochondria isolated from human muscle biopsies with the aim to obtain a comprehensive overview of mitochondrial phosphoproteins....... Future comparative phosphoproteome analysis of mitochondria from healthy and diseased individuals will provide insights into the role of abnormal phosphorylation in pathologies, such as type 2 diabetes....... in insulin resistance. We also assigned phosphorylation sites in mitochondrial proteins involved in amino acid degradation, importers and transporters, calcium homeostasis, and apoptosis. Bioinformatics analysis of kinase motifs revealed that many of these mitochondrial phosphoproteins are substrates...

  7. Integrative Network Analysis Combined with Quantitative Phosphoproteomics Reveals Transforming Growth Factor-beta Receptor type-2 (TGFBR2) as a Novel Regulator of Glioblastoma Stem Cell Properties.

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    Narushima, Yuta; Kozuka-Hata, Hiroko; Koyama-Nasu, Ryo; Tsumoto, Kouhei; Inoue, Jun-ichiro; Akiyama, Tetsu; Oyama, Masaaki

    2016-03-01

    Glioblastoma is one of the most malignant brain tumors with poor prognosis and their development and progression are known to be driven by glioblastoma stem cells. Although glioblastoma stem cells lose their cancer stem cell properties during cultivation in serum-containing medium, little is known about the molecular mechanisms regulating signaling alteration in relation to reduction of stem cell-like characteristics. To elucidate the global phosphorylation-related signaling events, we performed a SILAC-based quantitative phosphoproteome analysis of serum-induced dynamics in glioblastoma stem cells established from the tumor tissues of the patient. Among a total of 2876 phosphorylation sites on 1584 proteins identified in our analysis, 732 phosphorylation sites on 419 proteins were regulated through the alteration of stem cell-like characteristics. The integrative computational analyses based on the quantified phosphoproteome data revealed the relevant changes of phosphorylation levels regarding the proteins associated with cytoskeleton reorganization such as Rho family GTPase and Intermediate filament signaling, in addition to transforming growth factor-β receptor type-2 (TGFBR2) as a prominent upstream regulator involved in the serum-induced phosphoproteome regulation. The functional association of transforming growth factor-β receptor type-2 with stem cell-like properties was experimentally validated through signaling perturbation using the corresponding inhibitors, which indicated that transforming growth factor-β receptor type-2 could play an important role as a novel cell fate determinant in glioblastoma stem cell regulation. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  8. Quantitative Phosphoproteomic Analysis of Soybean Root Hairs Inoculated with Bradyrhizobium japonicum

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    Nguyen, Tran H.; Brechenmacher, Laurent; Aldrich, Joshua T.; Clauss, Therese RW; Gritsenko, Marina A.; Hixson, Kim K.; Libault, Marc; Tanaka, Kiwamu; Yang, Feng; Yao, Qiuming; Pasa-Tolic, Ljiljana; Xu, Dong; Nguyen, Henry T.; Stacey, Gary

    2012-11-11

    Root hairs are single hair-forming cells on roots that function to increase root surface area, enhancing water and nutrient uptake. In leguminous plants, root hairs also play a critical role as the site of infection by symbiotic nitrogen fixing rhizobia, leading to the formation of a novel organ, the nodule. The initial steps in the rhizobia-root hair infection process are known to involve specific receptor kinases and subsequent kinase cascades. Here, we characterize the phosphoproteome of the root hairs and the corresponding stripped roots (i.e., roots from which root hairs were removed) during rhizobial colonization and infection to gain insight into the molecular mechanism of root hair cell biology. We chose soybean (Glycine max L.), one of the most important crop plants in the legume family, for this study because of its larger root size, which permits isolation of sufficient root hair material for phosphoproteomic analysis. Phosphopeptides derived from root hairs and stripped roots, mock inoculated or inoculated with the soybean-specific rhizobium Bradyrhizobium japonicum, were labeled with the isobaric tag 8-plex ITRAQ, enriched using Ni-NTA magnetic beads and subjected to nRPLC-MS/MS analysis using HCD and decision tree guided CID/ETD strategy. A total of 1,625 unique phosphopeptides, spanning 1,659 non-redundant phosphorylation sites, were detected from 1,126 soybean phosphoproteins. Among them, 273 phosphopeptides corresponding to 240 phosphoproteins were found to be significantly regulated (>1.5 fold abundance change) in response to inoculation with B. japonicum. The data reveal unique features of the soybean root hair phosphoproteome, including root hair and stripped root-specific phosphorylation suggesting a complex network of kinase-substrate and phosphatase-substrate interactions in response to rhizobial inoculation.

  9. Novel Host Proteins and Signaling Pathways in Enteropathogenic E. coli Pathogenesis Identified by Global Phosphoproteome Analysis*

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    Scholz, Roland; Imami, Koshi; Scott, Nichollas E.; Trimble, William S.; Foster, Leonard J.; Finlay, B. Brett

    2015-01-01

    Enteropathogenic Escherichia coli (EPEC) uses a type III secretion system (T3SS) to directly translocate effector proteins into host cells where they play a pivotal role in subverting host cell signaling needed for disease. However, our knowledge of how EPEC affects host protein phosphorylation is limited to a few individual protein studies. We employed a quantitative proteomics approach to globally map alterations in the host phosphoproteome during EPEC infection. By characterizing host phosphorylation events at various time points throughout infection, we examined how EPEC dynamically impacts the host phosphoproteome over time. This experimental setup also enabled identification of T3SS-dependent and -independent changes in host phosphorylation. Specifically, T3SS-regulated events affected various cellular processes that are known EPEC targets, including cytoskeletal organization, immune signaling, and intracellular trafficking. However, the involvement of phosphorylation in these events has thus far been poorly studied. We confirmed the MAPK family as an established key host player, showed its central role in signal transduction during EPEC infection, and extended the repertoire of known signaling hubs with previously unrecognized proteins, including TPD52, CIN85, EPHA2, and HSP27. We identified altered phosphorylation of known EPEC targets, such as cofilin, where the involvement of phosphorylation has so far been undefined, thus providing novel mechanistic insights into the roles of these proteins in EPEC infection. An overlap of regulated proteins, especially those that are cytoskeleton-associated, was observed when compared with the phosphoproteome of Shigella-infected cells. We determined the biological relevance of the phosphorylation of a novel protein in EPEC pathogenesis, septin-9 (SEPT9). Both siRNA knockdown and a phosphorylation-impaired SEPT9 mutant decreased bacterial adherence and EPEC-mediated cell death. In contrast, a phosphorylation

  10. Predicting Kinase Activity in Angiotensin Receptor Phosphoproteomes Based on Sequence-Motifs and Interactions

    DEFF Research Database (Denmark)

    Bøgebo, Rikke; Horn, Heiko; Olsen, Jesper V

    2014-01-01

    Recent progress in the understanding of seven-transmembrane receptor (7TMR) signalling has promoted the development of a new generation of pathway selective ligands. The angiotensin II type I receptor (AT1aR) is one of the most studied 7TMRs with respect to selective activation of the β-arrestin ......Recent progress in the understanding of seven-transmembrane receptor (7TMR) signalling has promoted the development of a new generation of pathway selective ligands. The angiotensin II type I receptor (AT1aR) is one of the most studied 7TMRs with respect to selective activation of the β......-arrestin dependent signalling. Two complimentary global phosphoproteomics studies have analyzed the complex signalling induced by the AT1aR. Here we integrate the data sets from these studies and perform a joint analysis using a novel method for prediction of differential kinase activity from phosphoproteomics data....... The method builds upon NetworKIN, which applies sophisticated linear motif analysis in combination with contextual network modelling to predict kinase-substrate associations with high accuracy and sensitivity. These predictions form the basis for subsequently nonparametric statistical analysis to identify...

  11. Analysis of EGFR signaling pathway in nasopharyngeal carcinoma cells by quantitative phosphoproteomics

    Directory of Open Access Journals (Sweden)

    He Qiu-Yan

    2011-06-01

    Full Text Available Abstract Background The epidermal growth factor receptor (EGFR is usually overexpressed in nasopharyngeal carcinoma (NPC and is associated with pathogenesis of NPC. However, the downstream signaling proteins of EGFR in NPC have not yet been completely understood at the system level. The aim of this study was identify novel downstream proteins of EGFR signaling pathway in NPC cells. Results We analyzed EGFR-regulated phosphoproteome in NPC CNE2 cells using 2D-DIGE and mass spectrometry analysis after phosphoprotein enrichment. As a result, 33 nonredundant phosphoproteins including five known EGFR-regulated proteins and twenty-eight novel EGFR-regulated proteins in CNE2 were identified, three differential phosphoproteins were selectively validated, and two differential phosphoproteins (GSTP1 and GRB2 were showed interacted with phospho-EGFR. Bioinformatics analysis showed that 32 of 33 identified proteins contain phosphorylation modification sites, and 17 identified proteins are signaling proteins. GSTP1, one of the EGFR-regulated proteins, associated with chemoresistance was analyzed. The results showed that GSTP1 could contribute to paclitaxel resistance in EGF-stimulated CNE2 cells. Furthermore, an EGFR signaling network based on the identified EGFR-regulated phosphoproteins were constructed using Pathway Studio 5.0 software, which includes canonical and novel EGFR-regulated proteins and implicates the possible biological roles for those proteins. Conclusion The data not only can extend our knowledge of canonical EGFR signaling, but also will be useful to understand the molecular mechanisms of EGFR in NPC pathogenesis and search therapeutic targets for NPC.

  12. Quantitative phosphoproteomics analysis of nitric oxide-responsive phosphoproteins in cotton leaf.

    Directory of Open Access Journals (Sweden)

    Shuli Fan

    Full Text Available Knowledge of phosphorylation events and their regulation is crucial to understanding the functional biology of plant proteins, but very little is currently known about nitric oxide-responsive phosphorylation in plants. Here, we report the first large-scale, quantitative phosphoproteome analysis of cotton (Gossypium hirsutum treated with sodium nitroprusside (nitric oxide donor by utilizing the isobaric tag for relative and absolute quantitation (iTRAQ method. A total of 1315 unique phosphopeptides, spanning 1528 non-redundant phosphorylation sites, were detected from 1020 cotton phosphoproteins. Among them, 183 phosphopeptides corresponding to 167 phosphoproteins were found to be differentially phosphorylated in response to sodium nitroprusside. Several of the phosphorylation sites that we identified, including RQxS, DSxE, TxxxxSP and SPxT, have not, to our knowledge, been reported to be protein kinase sites in other species. The phosphoproteins identified are involved in a wide range of cellular processes, including signal transduction, RNA metabolism, intracellular transport and so on. This study reveals unique features of the cotton phosphoproteome and provides new insight into the biochemical pathways that are regulated by nitric oxide.

  13. Comparative gel-based phosphoproteomics in response to signaling molecules

    KAUST Repository

    Marondedze, Claudius

    2013-09-03

    The gel-based proteomics approach is a valuable technique for studying the characteristics of proteins. This technique has diverse applications ranging from analysis of a single protein to the study of the total cellular proteins. Further, protein quality and to some extent distribution can be first assessed by means of one-dimensional gel electrophoresis and then more informatively, for comparative analysis, using the two-dimensional gel electrophoresis technique. Here, we describe how to take advantage of the availability of fluorescent dyes to stain for a selective class of proteins on the same gel for the detection of both phospho- and total proteomes. This enables the co-detection of phosphoproteins as well as total proteins from the same gel and is accomplished by utilizing two different fluorescent stains, the ProQ-Diamond, which stains only phosphorylated proteins, and Sypro Ruby, which stains the entire subset of proteins. This workflow can be applied to gain insights into the regulatory mechanisms induced by signaling molecules such as cyclic nucleotides through the quantification and subsequent identification of responsive phospho- and total proteins. © Springer Science+Business Media New York 2013.

  14. Quantitative Analysis of Human Pluripotency and Neural Specification by In-Depth (PhosphoProteomic Profiling

    Directory of Open Access Journals (Sweden)

    Ilyas Singec

    2016-09-01

    Full Text Available Controlled differentiation of human embryonic stem cells (hESCs can be utilized for precise analysis of cell type identities during early development. We established a highly efficient neural induction strategy and an improved analytical platform, and determined proteomic and phosphoproteomic profiles of hESCs and their specified multipotent neural stem cell derivatives (hNSCs. This quantitative dataset (nearly 13,000 proteins and 60,000 phosphorylation sites provides unique molecular insights into pluripotency and neural lineage entry. Systems-level comparative analysis of proteins (e.g., transcription factors, epigenetic regulators, kinase families, phosphorylation sites, and numerous biological pathways allowed the identification of distinct signatures in pluripotent and multipotent cells. Furthermore, as predicted by the dataset, we functionally validated an autocrine/paracrine mechanism by demonstrating that the secreted protein midkine is a regulator of neural specification. This resource is freely available to the scientific community, including a searchable website, PluriProt.

  15. Novel Host Proteins and Signaling Pathways in Enteropathogenic E. coli Pathogenesis Identified by Global Phosphoproteome Analysis.

    Science.gov (United States)

    Scholz, Roland; Imami, Koshi; Scott, Nichollas E; Trimble, William S; Foster, Leonard J; Finlay, B Brett

    2015-07-01

    Enteropathogenic Escherichia coli (EPEC) uses a type III secretion system (T3SS) to directly translocate effector proteins into host cells where they play a pivotal role in subverting host cell signaling needed for disease. However, our knowledge of how EPEC affects host protein phosphorylation is limited to a few individual protein studies. We employed a quantitative proteomics approach to globally map alterations in the host phosphoproteome during EPEC infection. By characterizing host phosphorylation events at various time points throughout infection, we examined how EPEC dynamically impacts the host phosphoproteome over time. This experimental setup also enabled identification of T3SS-dependent and -independent changes in host phosphorylation. Specifically, T3SS-regulated events affected various cellular processes that are known EPEC targets, including cytoskeletal organization, immune signaling, and intracellular trafficking. However, the involvement of phosphorylation in these events has thus far been poorly studied. We confirmed the MAPK family as an established key host player, showed its central role in signal transduction during EPEC infection, and extended the repertoire of known signaling hubs with previously unrecognized proteins, including TPD52, CIN85, EPHA2, and HSP27. We identified altered phosphorylation of known EPEC targets, such as cofilin, where the involvement of phosphorylation has so far been undefined, thus providing novel mechanistic insights into the roles of these proteins in EPEC infection. An overlap of regulated proteins, especially those that are cytoskeleton-associated, was observed when compared with the phosphoproteome of Shigella-infected cells. We determined the biological relevance of the phosphorylation of a novel protein in EPEC pathogenesis, septin-9 (SEPT9). Both siRNA knockdown and a phosphorylation-impaired SEPT9 mutant decreased bacterial adherence and EPEC-mediated cell death. In contrast, a phosphorylation

  16. Plant Phosphoproteomics: Analysis of Plasma Membrane Transporters by Mass Spectrometry

    DEFF Research Database (Denmark)

    Ye, Juanying; Rudashevskaya, Elena; Young, Clifford

      Phosphorylation is a key regulatory factor in all aspects of eukaryotic biology including the regulation of plant membrane-bound transport proteins. To date, mass spectrometry (MS) has been introduced as powerful technology for study of post translational modifications (PTMs), including protein...... phosphorylation. Due to the low abundance of phosphoprotein, the specific enrichment prior to MS analysis is necessary. Plant proton pump (H+-ATPase) is an enzyme controls the major transport processes in the plant, such as root nutrient uptake. Moreover, this pump has been proposed to be involved in other...... important physiological functions, such as stomata aperture, cell elongation, or cellular pH regulation. It is known that the activity of plant plasma membrane H+-ATPase is regulated by phosphorylation. Therefore, we first investigated the phosphorylation profile of plant H+-ATPase by enriching...

  17. The Arabidopsis thaliana Cyclic-Nucleotide-Dependent Response – a Quantitative Proteomic and Phosphoproteomic Analysis

    KAUST Repository

    Alqurashi, May M.

    2013-11-01

    Protein phosphorylation governs many regulatory pathways and an increasing number of kinases, proteins that transfer phosphate groups, are in turn activated by cyclic nucleotides. One of the cyclic nucleotides, cyclic adenosine monophosphate (cAMP), has been shown to be a second messenger in abiotic and biotic stress responses. However, little is known about the precise role of cAMP in plants and in the down-stream activation of kinases, and hence cAMP-dependent phosphorylation. To increase our understanding of the role of cAMP, proteomic and phosphoproteomic profiles of Arabidopsis thaliana suspension culture cells were analyzed before and after treatment of cells with two different concentrations of 8-Bromo-cAMP (1 µM and 100 nM) and over a time-course of one hour. A comparative quantitative analysis was undertaken using two- dimensional gel electrophoresis and the Delta 2D software (DECODON) followed by protein spot identification by tandem mass spectrometry combined with Mascot and Scaffold. Differentially expressed proteins and regulated phosphoproteins were categorized according to their biological function using bioinformatics tools. The results revealed that the treatment with 1 µM and 100 nM 8-Bromo-cAMP was sufficient to induce specific concentration- and time-dependent changes at the proteome and phosphoproteome levels. In particular, different phosphorylation patterns were observed overtime preferentially affecting proteins in a number of functional categories, notably phosphatases, proteins that remove phosphate groups. This suggests that cAMP both transiently activates and deactivates proteins through specific phosphorylation events and provides new insight into biological mechanisms and functions at the systems level.

  18. In Vivo SILAC-Based Proteomics Reveals Phosphoproteome Changes during Mouse Skin Carcinogenesis

    NARCIS (Netherlands)

    Zanivan, S.; Meves, A.; Behrendt, K.; Schoof, E.M.; Neilson, L.J.; Cox, J.; Tang, H.R.; Kalna, G.; Ree, J.H. van; Deursen, J.M.A. van; Trempus, C.S.; Machesky, L.M.; Linding, R.; Wickstrom, S.A.; Fassler, R.; Mann, M.

    2013-01-01

    Cancer progresses through distinct stages, and mouse models recapitulating traits of this progression are frequently used to explore genetic, morphological, and pharmacological aspects of tumor development. To complement genomic investigations of this process, we here quantify phosphoproteomic

  19. Quantitative phosphoproteomics using acetone-based peptide labeling: Method evaluation and application to a cardiac ischemia/reperfusion model

    Science.gov (United States)

    Wijeratne, Aruna B.; Manning, Janet R.; Schultz, Jo El J.; Greis, Kenneth D.

    2013-01-01

    Mass spectrometry (MS) techniques to globally profile protein phosphorylation in cellular systems that are relevant to physiological or pathological changes have been of significant interest in biological research. In this report, an MS-based strategy utilizing an inexpensive acetone-based peptide labeling technique known as reductive alkylation by acetone (RABA) for quantitative phosphoproteomics was explored to evaluate its capacity. Since the chemistry for RABA-labeling for phosphorylation profiling had not been previously reported, it was first validated using a standard phosphoprotein and identical phosphoproteomes from cardiac tissue extracts. A workflow was then utilized to compare cardiac tissue phosphoproteomes from mouse hearts not expressing FGF2 vs. hearts expressing low molecular weight fibroblast growth factor-2 (LMW FGF2) to relate low molecular weight fibroblast growth factor-2 (LMW FGF2) mediated cardioprotective phenomena induced by ischemia/reperfusion (I/R) injury of hearts, with downstream phosphorylation changes in LMW FGF2 signaling cascades. Statistically significant phosphorylation changes were identified at 14 different sites on 10 distinct proteins including some with mechanisms already established for LMW FGF2-mediated cardioprotective signaling (e.g. connexin-43), some with new details linking LMW FGF2 to the cardioprotective mechanisms (e.g. cardiac myosin binding protein C or cMyBPC), and also several new downstream effectors not previously recognized for cardio-protective signaling by LMW FGF2. Additionally, one of the phosphopeptides, cMyBPC/pSer-282, identified was further verified with site-specific quantification using an SRM (selected reaction monitoring)-based approach that also relies on isotope labeling of a synthetic phosphopeptide with deuterated acetone as an internal standard. Overall, this study confirms that the inexpensive acetone-based peptide labeling can be used in both exploratory and targeted quantification

  20. Quantitative phosphoproteomic analysis reveals shared and specific targets of Arabidopsis MPK3, MPK4 and MPK6

    KAUST Repository

    Rayapuram, Naganand

    2017-11-23

    In Arabidopsis, mitogen-activated protein kinases MPK3, MPK4 and MPK6 constitute essential relays for a variety of functions including cell division, development and innate immunity. While some substrates of MPK3, MPK4 and MPK6 have been identified, the picture is still far from complete. To identify substrates of these MAPKs likely involved in cell division, growth and development we compared the phosphoproteomes of wild-type and mpk3, mpk4 and mpk6. To study the function of these MAPKs in innate immunity, we analyzed their phosphoproteomes following microbe-associated molecular pattern (MAMP) treatment. Partially overlapping substrates were retrieved for all three MAPKs, showing target specificity to one, two or all three MAPKs in different biological processes. More precisely, our results illustrate the fact that the entity to be defined as a specific or a shared substrate for MAPKs is not a phosphoprotein but a particular (S/T)P phosphorylation site in a given protein. As a whole, 152 peptides were identified to be differentially phosphorylated in response to MAMP treatment and/or when compared between genotypes and 70 of them could be classified as putative MAPK targets. Biochemical analysis of a number of putative MAPK substrates by phosphorylation and interaction assays confirmed the global phosphoproteome approach. Our study also expands the set of MAPK substrates to involve other protein kinases, including calcium-dependent (CDPK) and sugar non-fermenting (SnRK) protein kinases.

  1. Quantitative phosphoproteomic analysis reveals system-wide signaling pathways downstream of SDF-1/CXCR4 in breast cancer stem cells

    Science.gov (United States)

    Yi, Tingfang; Zhai, Bo; Yu, Yonghao; Kiyotsugu, Yoshikawa; Raschle, Thomas; Etzkorn, Manuel; Seo, Hee-Chan; Nagiec, Michal; Luna, Rafael E.; Reinherz, Ellis L.; Blenis, John; Gygi, Steven P.; Wagner, Gerhard

    2014-01-01

    Breast cancer is the leading cause of cancer-related mortality in women worldwide, with an estimated 1.7 million new cases and 522,000 deaths around the world in 2012 alone. Cancer stem cells (CSCs) are essential for tumor reoccurrence and metastasis which is the major source of cancer lethality. G protein-coupled receptor chemokine (C-X-C motif) receptor 4 (CXCR4) is critical for tumor metastasis. However, stromal cell-derived factor 1 (SDF-1)/CXCR4–mediated signaling pathways in breast CSCs are largely unknown. Using isotope reductive dimethylation and large-scale MS-based quantitative phosphoproteome analysis, we examined protein phosphorylation induced by SDF-1/CXCR4 signaling in breast CSCs. We quantified more than 11,000 phosphorylation sites in 2,500 phosphoproteins. Of these phosphosites, 87% were statistically unchanged in abundance in response to SDF-1/CXCR4 stimulation. In contrast, 545 phosphosites in 266 phosphoproteins were significantly increased, whereas 113 phosphosites in 74 phosphoproteins were significantly decreased. SDF-1/CXCR4 increases phosphorylation in 60 cell migration- and invasion-related proteins, of them 43 (>70%) phosphoproteins are unrecognized. In addition, SDF-1/CXCR4 upregulates the phosphorylation of 44 previously uncharacterized kinases, 8 phosphatases, and 1 endogenous phosphatase inhibitor. Using computational approaches, we performed system-based analyses examining SDF-1/CXCR4–mediated phosphoproteome, including construction of kinase–substrate network and feedback regulation loops downstream of SDF-1/CXCR4 signaling in breast CSCs. We identified a previously unidentified SDF-1/CXCR4-PKA-MAP2K2-ERK signaling pathway and demonstrated the feedback regulation on MEK, ERK1/2, δ-catenin, and PPP1Cα in SDF-1/CXCR4 signaling in breast CSCs. This study gives a system-wide view of phosphorylation events downstream of SDF-1/CXCR4 signaling in breast CSCs, providing a resource for the study of CSC-targeted cancer therapy. PMID

  2. Ultradeep Human Phosphoproteome Reveals a Distinct Regulatory Nature of Tyr and Ser/Thr-Based Signaling

    Directory of Open Access Journals (Sweden)

    Kirti Sharma

    2014-09-01

    Full Text Available Regulatory protein phosphorylation controls normal and pathophysiological signaling in eukaryotic cells. Despite great advances in mass-spectrometry-based proteomics, the extent, localization, and site-specific stoichiometry of this posttranslational modification (PTM are unknown. Here, we develop a stringent experimental and computational workflow, capable of mapping more than 50,000 distinct phosphorylated peptides in a single human cancer cell line. We detected more than three-quarters of cellular proteins as phosphoproteins and determined very high stoichiometries in mitosis or growth factor signaling by label-free quantitation. The proportion of phospho-Tyr drastically decreases as coverage of the phosphoproteome increases, whereas Ser/Thr sites saturate only for technical reasons. Tyrosine phosphorylation is maintained at especially low stoichiometric levels in the absence of specific signaling events. Unexpectedly, it is enriched on higher-abundance proteins, and this correlates with the substrate KM values of tyrosine kinases. Our data suggest that P-Tyr should be considered a functionally separate PTM of eukaryotic proteomes.

  3. Identifications of Putative PKA Substrates with Quantitative Phosphoproteomics and Primary-Sequence-Based Scoring.

    Science.gov (United States)

    Imamura, Haruna; Wagih, Omar; Niinae, Tomoya; Sugiyama, Naoyuki; Beltrao, Pedro; Ishihama, Yasushi

    2017-04-07

    Protein kinase A (PKA or cAMP-dependent protein kinase) is a serine/threonine kinase that plays essential roles in the regulation of proliferation, differentiation, and apoptosis. To better understand the functions of PKA, it is necessary to elucidate the direct interplay between PKA and their substrates in living human cells. To identify kinase target substrates in a high-throughput manner, we first quantified the change of phosphoproteome in the cells of which PKA activity was perturbed by drug stimulations. LC-MS/MS analyses identified 2755 and 3191 phosphopeptides from experiments with activator or inhibitor of PKA. To exclude potential indirect targets of PKA, we built a computational model to characterize the kinase sequence specificity toward the substrate target site based on known kinase-substrate relationships. Finally, by combining the sequence recognition model with the quantitative changes in phosphorylation measured in the two drug perturbation experiments, we identified 29 reliable candidates of PKA targeting residues in living cells including 8 previously known substrates. Moreover, 18 of these sites were confirmed to be site-specifically phosphorylated in vitro. Altogether this study proposed a confident list of PKA substrate candidates, expanding our knowledge of PKA signaling network.

  4. Online automated in vivo zebrafish phosphoproteomics: from large-scale analysis down to a single embryo.

    Science.gov (United States)

    Lemeer, Simone; Pinkse, Martijn W H; Mohammed, Shabaz; van Breukelen, Bas; den Hertog, Jeroen; Slijper, Monique; Heck, Albert J R

    2008-04-01

    In the developing embryo, as in many other biological processes, complex signaling pathways are under tight control of reversible phosphorylation, guiding cell proliferation, differentiation, and growth. Therefore the large-scale identification of signaling proteins and their post-translational modifications is crucial to understand the proteome biology of the developing zebrafish embryo. Here, we used an automated, robust, and sensitive online TiO 2-based LC-MS/MS setup to enrich for phosphorylated peptides from 1 day old zebrafish embryos. We identified, with high confidence, 1067 endogenous phosphorylation sites in a sample taken from 60 embryos (approximately 180 microg), 321 from 10 embryos, and 47 phosphorylation sites from a single embryo, illustrating the sensitivity of the method. This data set, representing by far the largest for zebrafish, was further exploited by searching for serine/threonine or tyrosine kinase motifs using Scansite. For one-third of the identified phosphopeptides a potential kinase motif could be predicted, where it appeared that Cdk5 kinase, p38MAPK, PKA, and Casein Kinase 2 substrates were the most predominant motifs present, underpinning the importance of these kinases in signaling pathways in embryonic development. The phosphopeptide data set was further interrogated using alignments with phosphopeptides identified in recent large-scale phosphoproteomics screens in human and mouse samples. These alignments revealed conservation of phosphorylation sites in several proteins suggesting preserved function in embryonic development.

  5. Time-resolved quantitative phosphoproteomics

    DEFF Research Database (Denmark)

    Verano-Braga, Thiago; Schwämmle, Veit; Sylvester, Marc

    2012-01-01

    proteins involved in the Ang-(1-7) signaling, we performed a mass spectrometry-based time-resolved quantitative phosphoproteome study of human aortic endothelial cells (HAEC) treated with Ang-(1-7). We identified 1288 unique phosphosites on 699 different proteins with 99% certainty of correct peptide...

  6. In Vivo SILAC-Based Proteomics Reveals Phosphoproteome Changes during Mouse Skin Carcinogenesis

    OpenAIRE

    Zanivan, Sara; Meves, Alexander; Behrendt, Kristina; Schoof, Erwin M.; Neilson, Lisa J.; Cox, Jürgen; Tang, Hao R.; Kalna, Gabriela; van Ree, Janine H.; van Deursen, Jan M.; Trempus, Carol S.; Machesky, Laura M.; Linding, Rune; Wickström, Sara A.; Fässler, Reinhard

    2013-01-01

    Cancer progresses through distinct stages, and mouse models recapitulating traits of this progression are frequently used to explore genetic, morphological, and pharmacological aspects of tumor development. To complement genomic investigations of this process, we here quantify phosphoproteomic changes in skin cancer development using the SILAC mouse technology coupled to high-resolution mass spectrometry. We distill protein expression signatures from our data that distinguish between skin can...

  7. Sample preparation for phosphoproteomic analysis of circadian time series in Arabidopsis thaliana.

    Science.gov (United States)

    Krahmer, Johanna; Hindle, Matthew M; Martin, Sarah F; Le Bihan, Thierry; Millar, Andrew J

    2015-01-01

    Systems biological approaches to study the Arabidopsis thaliana circadian clock have mainly focused on transcriptomics while little is known about the proteome, and even less about posttranslational modifications. Evidence has emerged that posttranslational protein modifications, in particular phosphorylation, play an important role for the clock and its output. Phosphoproteomics is the method of choice for a large-scale approach to gain more knowledge about rhythmic protein phosphorylation. Recent plant phosphoproteomics publications have identified several thousand phosphopeptides. However, the methods used in these studies are very labor-intensive and therefore not suitable to apply to a well-replicated circadian time series. To address this issue, we present and compare different strategies for sample preparation for phosphoproteomics that are compatible with large numbers of samples. Methods are compared regarding number of identifications, variability of quantitation, and functional categorization. We focus on the type of detergent used for protein extraction as well as methods for its removal. We also test a simple two-fraction separation of the protein extract. © 2015 Elsevier Inc. All rights reserved.

  8. Quantitative phosphoproteomic analysis of early seed development in rice (Oryza sativa L.).

    Science.gov (United States)

    Qiu, Jiehua; Hou, Yuxuan; Tong, Xiaohong; Wang, Yifeng; Lin, Haiyan; Liu, Qing; Zhang, Wen; Li, Zhiyong; Nallamilli, Babi R; Zhang, Jian

    2016-02-01

    Rice (Oryza sativa L.) seed serves as a major food source for over half of the global population. Though it has been long recognized that phosphorylation plays an essential role in rice seed development, the phosphorylation events and dynamics in this process remain largely unknown so far. Here, we report the first large scale identification of rice seed phosphoproteins and phosphosites by using a quantitative phosphoproteomic approach. Thorough proteomic studies in pistils and seeds at 3, 7 days after pollination resulted in the successful identification of 3885, 4313 and 4135 phosphopeptides respectively. A total of 2487 proteins were differentially phosphorylated among the three stages, including Kip related protein 1, Rice basic leucine zipper factor 1, Rice prolamin box binding factor and numerous other master regulators of rice seed development. Moreover, differentially phosphorylated proteins may be extensively involved in the biosynthesis and signaling pathways of phytohormones such as auxin, gibberellin, abscisic acid and brassinosteroid. Our results strongly indicated that protein phosphorylation is a key mechanism regulating cell proliferation and enlargement, phytohormone biosynthesis and signaling, grain filling and grain quality during rice seed development. Overall, the current study enhanced our understanding of the rice phosphoproteome and shed novel insight into the regulatory mechanism of rice seed development.

  9. Phosphoproteome analysis reveals new drought response and defense mechanisms of seedling leaves in bread wheat (Triticum aestivum L.).

    Science.gov (United States)

    Zhang, Ming; Lv, Dongwen; Ge, Pei; Bian, Yanwei; Chen, Guanxing; Zhu, Gengrui; Li, Xiaohui; Yan, Yueming

    2014-09-23

    Drought is a major form of abiotic stress that significantly affects plant growth and development. In this study, we performed the first phosphoproteome analysis of seedling leaves from two bread wheat cultivars (Hanxuan 10 and Ningchun 47) subjected to drought stress. As a result, a total of 191 and 251 unique phosphopeptides, representing 173 and 227 phosphoproteins in two cultivars, respectively, were identified as being significant changes in phosphorylation level (SCPL) under drought stress. Through the comparison of SCPL phosphoproteins between two cultivars, 31 common SCPL phosphoproteins were found in both cultivars. Function analysis showed that the SCPL phosphoproteins in the two cultivars are mainly involved in three biological processes: RNA transcription/processing, stress/detoxification/defense, and signal transduction. Further analyses revealed that some SCPL phosphoproteins may play key roles in signal transduction and the signaling cascade under drought stress. Furthermore, some phosphoproteins related to drought tolerance and osmotic regulation exhibited significant phosphorylation changes. This study used a series of bioinformatics tools to profile the phosphorylation status of wheat seedling leaves under drought stress with greater accuracy. Drought is of the most studied abiotic stresses, because it severely restricts the development and yield of plants. In this study, large numbers of stress-related phosphoproteins are identified from the two bread wheat cultivars. These phosphoproteins contribute to signal transduction, osmotic regulation and ROS scavenging under water stress. This work provides a detailed insight into the mechanisms of drought response and defense in bread wheat from the perspective of phosphoproteomics, and identifies some important drought-tolerant candidates for further transgenosis study and incorporation into the breeding of resistant cultivars. Copyright © 2014 Elsevier B.V. All rights reserved.

  10. Phosphoproteomic Analysis Identifies Signaling Pathways Regulated by Curcumin in Human Colon Cancer Cells.

    Science.gov (United States)

    Sato, Tatsuhiro; Higuchi, Yutaka; Shibagaki, Yoshio; Hattori, Seisuke

    2017-09-01

    Curcumin, a major polyphenol of the spice turmeric, acts as a potent chemopreventive and chemotherapeutic agent in several cancer types, including colon cancer. Although various proteins have been shown to be affected by curcumin, how curcumin exerts its anticancer activity is not fully understood. Phosphoproteomic analyses were performed using SW480 and SW620 human colon cancer cells to identify curcumin-affected signaling pathways. Curcumin inhibited the growth of the two cell lines in a dose-dependent manner. Thirty-nine curcumin-regulated phosphoproteins were identified, five of which are involved in cancer signaling pathways. Detailed analyses revealed that the mTORC1 and p53 signaling pathways are main targets of curcumin. Our results provide insight into the molecular mechanisms of the anticancer activities of curcumin and future molecular targets for its clinical application. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  11. Technologies and challenges in large-scale phosphoproteomics

    DEFF Research Database (Denmark)

    Engholm-Keller, Kasper; Larsen, Martin Røssel

    2013-01-01

    Phosphorylation, the reversible addition of a phosphate group to amino acid side chains of proteins, is a fundamental regulator of protein activity, stability, and molecular interactions. Most cellular processes, such as inter- and intracellular signaling, protein synthesis, degradation......, and apoptosis, rely on phosphorylation. This PTM is thus involved in many diseases, rendering localization and assessment of extent of phosphorylation of major scientific interest. MS-based phosphoproteomics, which aims at describing all phosphorylation sites in a specific type of cell, tissue, or organism, has...... become the main technique for discovery and characterization of phosphoproteins in a nonhypothesis driven fashion. In this review, we describe methods for state-of-the-art MS-based analysis of protein phosphorylation as well as the strategies employed in large-scale phosphoproteomic experiments...

  12. Analytical strategies for phosphoproteomics

    DEFF Research Database (Denmark)

    Thingholm, Tine E; Jensen, Ole N; Larsen, Martin R

    2009-01-01

    sensitive and specific strategies. Today, most phosphoproteomic studies are conducted by mass spectrometric strategies in combination with phospho-specific enrichment methods. This review presents an overview of different analytical strategies for the characterization of phosphoproteins. Emphasis...

  13. Phosphoproteomics by mass spectrometry: insights, implications, applications and limitations.

    Science.gov (United States)

    Mayya, Viveka; Han, David K

    2009-12-01

    Phosphorylation of proteins is a predominant, reversible post-translational modification. It is central to a wide variety of physiological responses and signaling mechanisms. Recent advances have allowed the global scope of phosphorylation to be addressed by mass spectrometry using phosphoproteomic approaches. In this perspective, we discuss four aspects of phosphoproteomics: the insights and implications from recently published phosphoproteomic studies and the applications and limitations of current phosphoproteomic strategies. Since approximately 50,000 known phosphorylation sites do not yet have any ascribed function, we present our perspectives on a major function of protein phosphorylation that may be of predictive value in hypothesis-based investigations. Finally, we discuss strategies to measure the stoichiometry of phosphorylation in a proteome-wide manner that is not provided by current phosphoproteomic approaches.

  14. Analysis of T4SS-induced signaling by H. pylori using quantitative phosphoproteomics

    Directory of Open Access Journals (Sweden)

    Frithjof eGlowinski

    2014-07-01

    Full Text Available Helicobacter pylori is a Gram-negative bacterial pathogen colonizing the human stomach. Infection with H. pylori causes chronic inflammation of the gastric mucosa and may lead to peptic ulceration and/or gastric cancer. A major virulence determinant of H. pylori is the type IV secretion system (T4SS, which is used to inject the virulence factor CagA into the host cell, triggering a wide range of cellular signaling events. Here, we used a phosphoproteomic approach to investigate tyrosine signaling in response to host-pathogen interaction, using stable isotope labeling in cell culture (SILAC of AGS cells to obtain a differential picture between multiple infection conditions. Cells were infected with wild type H. pylori P12, a P12ΔCagA deletion mutant, and a P12ΔT4SS deletion mutant to compare signaling changes over time and in the absence of CagA or the T4SS. Tryptic peptides were enriched for tyrosine (Tyr phosphopeptides and analysed by nano-LC-Orbitrap MS. In total, 58 different phosphosites were found to be regulated following infection. The majority of phosphosites identified were kinases of the MAPK familiy. CagA and the T4SS were found to be key regulators of Tyr phosphosites. Our findings indicate that CagA primarily induces activation of ERK1 and integrin linked factors, whereas the T4SS primarily modulates JNK and p38 activation.

  15. Correlating phosphoproteomic signaling with castration resistant prostate cancer survival through regression analysis.

    Science.gov (United States)

    Lescarbeau, Reynald; Kaplan, David L

    2014-03-04

    Prostate cancer most commonly presents as initially castration dependent, however in a minority of patients the disease will progress to a state of castration resistance. Here, approaches for correlating alterations in the phosphoproteome with androgen independent cell survival in the LNCaP, PC3, and MDa-PCa-2b cell lines are discussed. The performance of the regression techniques multiple linear, ridge, principal component, and partial least squares regression is compared. The predictive performance of these algorithms over randomized data sets and using the Akaike Information Criterion is explored, and principal component and partial least squares regression are found to outperform other regression approaches. The effect of altering the number of features versus observations on the R(2) value and predictive performance is also examined using the partial least squares regression model. Utilizing these approaches "drivers" of castration resistant disease can be identified whose modulation alters phenotypic outcomes. These data provide an empirical comparison of the various considerations when statistically analyzing phosphorylation data with the aim of correlating with phenotypic outcomes.

  16. Quantitative Phosphoproteomic Analysis Provides Insight into the Response to Short-Term Drought Stress in Ammopiptanthus mongolicus Roots

    Directory of Open Access Journals (Sweden)

    Huigai Sun

    2017-10-01

    Full Text Available Drought is one of the major abiotic stresses that negatively affects plant growth and development. Ammopiptanthus mongolicus is an ecologically important shrub in the mid-Asia desert region and used as a model for abiotic tolerance research in trees. Protein phosphorylation participates in the regulation of various biological processes, however, phosphorylation events associated with drought stress signaling and response in plants is still limited. Here, we conducted a quantitative phosphoproteomic analysis of the response of A. mongolicus roots to short-term drought stress. Data are available via the iProx database with project ID IPX0000971000. In total, 7841 phosphorylation sites were found from the 2019 identified phosphopeptides, corresponding to 1060 phosphoproteins. Drought stress results in significant changes in the abundance of 103 phosphopeptides, corresponding to 90 differentially-phosphorylated phosphoproteins (DPPs. Motif-x analysis identified two motifs, including [pSP] and [RXXpS], from these DPPs. Functional enrichment and protein-protein interaction analysis showed that the DPPs were mainly involved in signal transduction and transcriptional regulation, osmotic adjustment, stress response and defense, RNA splicing and transport, protein synthesis, folding and degradation, and epigenetic regulation. These drought-corresponsive phosphoproteins, and the related signaling and metabolic pathways probably play important roles in drought stress signaling and response in A. mongolicus roots. Our results provide new information for understanding the molecular mechanism of the abiotic stress response in plants at the posttranslational level.

  17. Analysis of the Rana catesbeiana tadpole tail fin proteome and phosphoproteome during T3-induced apoptosis: identification of a novel type I keratin.

    Science.gov (United States)

    Domanski, Dominik; Helbing, Caren C

    2007-08-06

    Thyroid hormones (THs) are vital in the maintenance of homeostasis and in the control of development. One postembryonic developmental process that is principally regulated by THs is amphibian metamorphosis. This process has been intensively studied at the genomic level yet very little information at the proteomic level exists. In addition, there is increasing evidence that changes in the phosphoproteome influence TH action. Here we identify components of the proteome and phosphoproteome in the tail fin that changed within 48 h of exposure of premetamorphic Rana catesbeiana tadpoles to 10 nM 3,5,3'-triiodothyronine (T3). To this end, we developed a cell and protein fractionation method combined with two-dimensional gel electrophoresis and phosphoprotein-specific staining. Altered proteins were identified using mass spectrometry (MS). We identified and cloned a novel Rana larval type I keratin, RLK I, which may be a target for caspase-mediated proteolysis upon exposure to T3. In addition, the RLK I transcript is reduced during T3-induced and natural metamorphosis which is consistent with a larval keratin. Furthermore, GILT, a protein involved in the immune system, is changed in phosphorylation state which is linked to its activation. Using a complementary MS technique for the analysis of differentially-expressed proteins, isobaric tags for relative and absolute quantitation (iTRAQ) revealed 15 additional proteins whose levels were altered upon T3 treatment. The success of identifying proteins whose levels changed upon T3 treatment with iTRAQ was enhanced through de novo sequencing of MS data and homology database searching. These proteins are involved in apoptosis, extracellular matrix structure, immune system, metabolism, mechanical function, and oxygen transport. We have demonstrated the ability to derive proteomics-based information from a model species for postembryonic development for which no genome information is currently available. The present study

  18. Analysis of the Rana catesbeiana tadpole tail fin proteome and phosphoproteome during T3-induced apoptosis: identification of a novel type I keratin

    Directory of Open Access Journals (Sweden)

    Helbing Caren C

    2007-08-01

    Full Text Available Abstract Background Thyroid hormones (THs are vital in the maintenance of homeostasis and in the control of development. One postembryonic developmental process that is principally regulated by THs is amphibian metamorphosis. This process has been intensively studied at the genomic level yet very little information at the proteomic level exists. In addition, there is increasing evidence that changes in the phosphoproteome influence TH action. Results Here we identify components of the proteome and phosphoproteome in the tail fin that changed within 48 h of exposure of premetamorphic Rana catesbeiana tadpoles to 10 nM 3,5,3'-triiodothyronine (T3. To this end, we developed a cell and protein fractionation method combined with two-dimensional gel electrophoresis and phosphoprotein-specific staining. Altered proteins were identified using mass spectrometry (MS. We identified and cloned a novel Rana larval type I keratin, RLK I, which may be a target for caspase-mediated proteolysis upon exposure to T3. In addition, the RLK I transcript is reduced during T3-induced and natural metamorphosis which is consistent with a larval keratin. Furthermore, GILT, a protein involved in the immune system, is changed in phosphorylation state which is linked to its activation. Using a complementary MS technique for the analysis of differentially-expressed proteins, isobaric tags for relative and absolute quantitation (iTRAQ revealed 15 additional proteins whose levels were altered upon T3 treatment. The success of identifying proteins whose levels changed upon T3 treatment with iTRAQ was enhanced through de novo sequencing of MS data and homology database searching. These proteins are involved in apoptosis, extracellular matrix structure, immune system, metabolism, mechanical function, and oxygen transport. Conclusion We have demonstrated the ability to derive proteomics-based information from a model species for postembryonic development for which no genome

  19. Proteomics and phosphoproteomics analysis of liver in male rats exposed to bisphenol A: Mechanism of hepatotoxicity and biomarker discovery.

    Science.gov (United States)

    Vahdati Hassani, Faezeh; Abnous, Khalil; Mehri, Soghra; Jafarian, Amirhossein; Birner-Gruenberger, Ruth; Yazdian Robati, Rezvan; Hosseinzadeh, Hossein

    2018-02-01

    Bisphenol A (BPA), discovered to be an artificial estrogen, has been shown to leach from some containers and mediate oxidative damage to cells and tissues and to be involved in reproductive disorders, obesity, diabetes, and liver dysfunction. In the current study, we investigated the effects of oral chronic exposure to low dose of BPA (0.5 mg kg -1 ) on the protein and phosphoprotein expression profiles in male Wistar rat liver using a gel-based proteomics approach based on two-dimensional gel electrophoresis followed by matrix-assisted laser desorption/ionization mass spectrometry identification. Our results showed that BPA exposure affected the levels of proteins and phosphoproteins involved in diverse biological processes associated with hepatotoxicity, fatty liver, and carcinoma. Moreover, we analyzed the effects of BPA on oxidative stress by assessing levels of malondialdehyde (MDA), a marker of lipid peroxidation, and reduced glutathione (GSH), a non-enzymatic antioxidant agent, in the liver. As expected BPA induced oxidative stress indicated by increased levels of MDA and decreased GSH content in the liver. In conclusion, chronic oral exposure of rats to BPA leads to increased oxidative stress in the liver and major alterations in the liver proteome and phosphoproteome, which may contribute to the pathophysiology of liver diseases. Copyright © 2017 Elsevier Ltd. All rights reserved.

  20. Robust phosphoproteome enrichment using monodisperse microsphere-based immobilized titanium (IV) ion affinity chromatography

    NARCIS (Netherlands)

    Zhou, H.; Ye, M.; Dong, J.; Corradini, E.; Cristobal, A.; Heck, A.J.R.; zou, H.; Mohammed, S.

    2013-01-01

    Mass spectrometry (MS)-based proteomics has become the preferred tool for the analysis of protein phosphorylation. To be successful at such an endeavor, there is a requirement for an efficient enrichment of phosphopeptides. This is necessary because of the substoichiometric nature of phosphorylation

  1. Phosphoproteomic Analysis of KSHV-Infected Cells Reveals Roles of ORF45-Activated RSK during Lytic Replication.

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    Denis Avey

    2015-07-01

    Full Text Available Kaposi's Sarcoma-Associated Herpesvirus (KSHV is an oncogenic virus which has adapted unique mechanisms to modulate the cellular microenvironment of its human host. The pathogenesis of KSHV is intimately linked to its manipulation of cellular signaling pathways, including the extracellular signal-regulated kinase (ERK mitogen-activated protein kinase (MAPK pathway. We have previously shown that KSHV ORF45 contributes to the sustained activation of both ERK and p90 ribosomal S6 kinase (RSK, a major functional mediator of ERK/MAPK signaling during KSHV lytic replication. ORF45-activated RSK is required for optimal KSHV lytic gene expression and progeny virion production, though the underlying mechanisms downstream of this activation are still unclear. We hypothesized that the activation of RSK by ORF45 causes differential phosphorylation of cellular and viral substrates, affecting biological processes essential for efficient KSHV lytic replication. Accordingly, we observed widespread and significant differences in protein phosphorylation upon induction of lytic replication. Mass-spectrometry-based phosphoproteomic screening identified putative substrates of ORF45-activated RSK in KSHV-infected cells. Bioinformatic analyses revealed that nuclear proteins, including several transcriptional regulators, were overrepresented among these candidates. We validated the ORF45/RSK-dependent phosphorylation of several putative substrates by employing KSHV BAC mutagenesis, kinase inhibitor treatments, and/or CRISPR-mediated knockout of RSK in KSHV-infected cells. Furthermore, we assessed the consequences of knocking out these substrates on ORF45/RSK-dependent regulation of gene expression and KSHV progeny virion production. Finally, we show data to support that ORF45 regulates the translational efficiency of a subset of viral/cellular genes with complex secondary structure in their 5' UTR. Altogether, these data shed light on the mechanisms by which KSHV ORF45

  2. Quantitative- and Phospho-Proteomic Analysis of the Yeast Response to the Tyrosine Kinase Inhibitor Imatinib to Pharmacoproteomics-Guided Drug Line Extension

    Science.gov (United States)

    dos Santos, Sandra C.; Mira, Nuno P.; Moreira, Ana S.

    2012-01-01

    Abstract Imatinib mesylate (IM) is a potent tyrosine kinase inhibitor used as front-line therapy in chronic myeloid leukemia, a disease caused by the oncogenic kinase Bcr-Abl. Although the clinical success of IM set a new paradigm in molecular-targeted therapy, the emergence of IM resistance is a clinically significant problem. In an effort to obtain new insights into the mechanisms of adaptation and tolerance to IM, as well as the signaling pathways potentially affected by this drug, we performed a two-dimensional electrophoresis-based quantitative- and phospho-proteomic analysis in the eukaryotic model Saccharomyces cerevisiae. We singled out proteins that were either differentially expressed or differentially phosphorylated in response to IM, using the phosphoselective dye Pro-Q® Diamond, and identified 18 proteins in total. Ten were altered only at the content level (mostly decreased), while the remaining 8 possessed IM-repressed phosphorylation. These 18 proteins are mainly involved in cellular carbohydrate processes (glycolysis/gluconeogenesis), translation, protein folding, ion homeostasis, and nucleotide and amino acid metabolism. Remarkably, all 18 proteins have human functional homologs. A role for HSP70 proteins in the response to IM, as well as decreased glycolysis as a metabolic marker of IM action are suggested, consistent with findings from studies in human cell lines. The previously-proposed effect of IM as an inhibitor of vacuolar H+-ATPase function was supported by the identification of an underexpressed protein subunit of this complex. Taken together, these findings reinforce the role of yeast as a valuable eukaryotic model for pharmacological studies and identification of new drug targets, with potential clinical implications in drug reassignment or line extension under a personalized medicine perspective. PMID:22775238

  3. Quantitative Phosphoproteome Analysis of Lysophosphatidic Acid Induced Chemotaxis applying Dual-step ¹⁸O Labeling Coupled with Immobilized Metal-ion Affinity Chromatography

    Energy Technology Data Exchange (ETDEWEB)

    Ding, Shi-Jian; Wang, Yingchun; Jacobs, Jon M.; Qian, Weijun; Yang, Feng; Tolmachev, Aleksey V.; Du, Xiuxia; Wang, Wei; Moore, Ronald J.; Monroe, Matthew E.; Purvine, Samuel O.; Waters, Katrina M.; Heibeck, Tyler H.; Adkins, Joshua N.; Camp, David G.; Klemke, Richard L.; Smith, Richard D.

    2008-10-01

    Reversible protein phosphorylation is a central cellular regulatory mechanism in modulating protein activity and propagating signals within cellular pathways and networks. Development of more effective methods for the simultaneous identification of phosphorylation sites and quantification of temporal changes in protein phosphorylation could provide important insights into molecular signaling mechanisms in a variety of different cellular processes. Here we present an integrated quantitative phosphoproteomics approach and its applications for comparative analysis of Cos-7 cells in response to lysophosphatidic acid (LPA) gradient stimulation. The approach combines trypsin-catalyzed 16O/18O labeling plus 16O/18O-methanol esterification labeling for quantitation, a macro- Immobilized Metal-ion Affinity Chromatography trap for phosphopeptide enrichment, and a monolithic capillary column with integrated electrospray emitter. LC separation and MS/MS is followed by neutral loss-dependent MS/MS/MS for phosphopeptide identification using a linear ion trap (LTQ)-FT mass spectrometer and complementary searching algorithms for interpreting MS/MS spectra. Protein phosphorylation involved in various signaling pathways of cell migration were identified and quantified, such as mitogen-activated protein kinase 1, dual-specificity mitogen-activated protein kinase kinase 2, and dual-specificity tyrosine-phosphorylation regulated kinase 1b, and a number of Rho GTPase-activating proteins. These results demonstrate the efficiency of this quantitative phosphoproteomics approach and its application for rapid discovery of phosphorylation events associated with gradient sensing and cell chemotaxis.

  4. Global analysis of phosphoproteome dynamics in embryonic development of zebrafish (Danio rerio).

    Science.gov (United States)

    Kwon, Oh Kwang; Kim, Sun Ju; Lee, You-Mie; Lee, Young-Hoon; Bae, Young-Seuk; Kim, Jin Young; Peng, Xiaojun; Cheng, Zhongyi; Zhao, Yingming; Lee, Sangkyu

    2016-01-01

    The zebrafish (Danio rerio) is a popular animal model used for studies on vertebrate development and organogenesis. Recent research has shown a similarity of approximately 70% between the human and zebrafish genomes and about 84% of human disease-causing genes have common ancestry with that of the zebrafish genes. Zebrafish embryos have a number of desirable features, including transparency, a large size, and rapid embryogenesis. Protein phosphorylation is a well-known PTM, which can carry out various biological functions. Recent MS developments have enabled the study of global phosphorylation patterns by using MS-based proteomics coupled with titanium dioxide phosphopeptide enrichment. In the present study, we identified 3500 nonredundant phosphorylation sites on 2166 phosphoproteins and quantified 1564 phosphoproteins in developing embryos of zebrafish. The distribution of Ser/Thr/Tyr phosphorylation sites in zebrafish embryos was found to be 88.9, 10.2, and 0.9%, respectively. A potential kinase motif was predicted using Motif-X analysis, for 80% of the identified phosphorylation sites, with the proline-directed motif appearing most frequently, and 35 phosphorylation sites having the pSF motif. In addition, we created six phosphoprotein clusters based on their dynamic pattern during the development of zebrafish embryos. Here, we report the largest dataset of phosphoproteins in zebrafish embryos and our results can be used for further studies on phosphorylation sites or phosphoprotein dynamics in zebrafish embryos. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  5. In Vivo Phosphoproteomics Analysis Reveals the Cardiac Targets of β-Adrenergic Receptor Signaling

    DEFF Research Database (Denmark)

    Lundby, Alicia; Andersen, Martin N; Steffensen, Annette B

    2013-01-01

    -X-X-pS/T), and integrative analysis of sequence motifs and interaction networks suggested that the kinases AMPK (adenosine 5'-monophosphate-activated protein kinase), Akt, and mTOR (mammalian target of rapamycin) mediate βAR signaling, in addition to the well-established pathways mediated by PKA (cyclic adenosine...

  6. Phosphoproteome analysis during larval development and metamorphosis in the spionid polychaete Pseudopolydora vexillosa

    KAUST Repository

    Chandramouli, Kondethimmanahalli

    2011-05-25

    Background: The metamorphosis of the spionid polychaete Pseudopolydora vexillosa includes spontaneous settlement onto soft-bottom habitats and morphogenesis that can be completed in a very short time. A previous study on the total changes to the proteome during the various developmental stages of P. vexillosa suggested that little or no de novo protein synthesis occurs during metamorphosis. In this study, we used multicolor fluorescence detection of proteins in 2-D gels for differential analysis of proteins and phosphoproteins to reveal the dynamics of post-translational modification proteins in this species. A combination of affinity chromatography, 2D-PAGE, and mass spectrometry was used to identify the phosphoproteins in pre-competent larvae, competent larvae, and newly metamorphosed juveniles. Results: We reproducibly detected 210, 492, and 172 phosphoproteins in pre-competent larvae, competent larvae, and newly metamorphosed juveniles, respectively. The highest percentage of phosphorylation was observed during the competent larval stage. About 64 stage-specific phosphoprotein spots were detected in the competent stage, and 32 phosphoproteins were found to be significantly differentially expressed in the three stages. We identified 38 phosphoproteins, 10 of which were differentially expressed during metamorphosis. These phosphoproteins belonged to six categories of biological processes: (1) development, (2) cell differentiation and integrity, (3) transcription and translation, (4) metabolism, (5) protein-protein interaction and proteolysis, and (6) receptors and enzymes. Conclusion: This is the first study to report changes in phosphoprotein expression patterns during the metamorphosis of the marine polychaete P. vexillosa. The higher degree of phosphorylation during the process of attaining competence to settle and metamorphose may be due to fast morphological transitions regulated by various mechanisms. Our data are consistent with previous studies showing a

  7. Simple and Reproducible Sample Preparation for Single-Shot Phosphoproteomics with High Sensitivity

    DEFF Research Database (Denmark)

    Jersie-Christensen, Rosa R.; Sultan, Abida; Olsen, Jesper V

    2016-01-01

    The traditional sample preparation workflow for mass spectrometry (MS)-based phosphoproteomics is time consuming and usually requires multiple steps, e.g., lysis, protein precipitation, reduction, alkylation, digestion, fractionation, and phosphopeptide enrichment. Each step can introduce chemical...... artifacts, in vitro protein and peptide modifications, and contaminations. Those often result in sample loss and affect the sensitivity, dynamic range and accuracy of the mass spectrometric analysis. Here we describe a simple and reproducible phosphoproteomics protocol, where lysis, denaturation, reduction......, and alkylation are performed in a single step, thus reducing sample loss and increasing reproducibility. Moreover, unlike standard cell lysis procedures the cell harvesting is performed at high temperatures (99 °C) and without detergents and subsequent need for protein precipitation. Phosphopeptides are enriched...

  8. Evaluation of HCD- and CID-type fragmentation within their respective detection platforms for murine phosphoproteomics.

    Science.gov (United States)

    Jedrychowski, Mark P; Huttlin, Edward L; Haas, Wilhelm; Sowa, Mathew E; Rad, Ramin; Gygi, Steven P

    2011-12-01

    Protein phosphorylation modulates a myriad of biological functions, and its regulation is vital for proper cellular activity. Mass spectrometry is the enabling tool for phosphopeptide analysis, where recent instrumentation advances in both speed and sensitivity in linear ion trap and orbitrap technologies may yield more comprehensive phosphoproteomic analyses in less time. Protein phosphorylation analysis by MS relies on structural information derived through controlled peptide fragmentation. Compared with traditional, ion-trap-based collision-induced dissociation (CID), a more recent type of fragmentation termed HCD (higher energy collisional dissociation) provides beam type CID tandem MS with detection of fragment ions at high resolution in the orbitrap mass analyzer. Here we compared HCD to traditional CID for large-scale phosphorylation analyses of murine brain under three separate experimental conditions. These included a same-precursor analysis where CID and HCD scans were performed back-to-back, separate analyses of a phosphotyrosine peptide immunoprecipitation experiment, and separate whole phosphoproteome analyses. HCD generally provided higher search engine scores with more peptides identified, thus out-performing CID for back-to-back experiments for most metrics tested. However, for phosphotyrosine IPs and in a full phosphoproteome study of mouse brain, the greater acquisition speed of CID-only analyses provided larger data sets. We reconciled our results with those in direct contradiction from Nagaraj N, D'Souza RCJ et al. (J. Proteome Res. 9:6786, 2010). We conclude, for large-scale phosphoproteomics, CID fragmentation with rapid detection in the ion trap still produced substantially richer data sets, but the back-to-back experiments demonstrated the promise of HCD and orbitrap detection for the future.

  9. Label-free quantitative analysis of the casein kinase 2-responsive phosphoproteome of the marine minimal model species Ostreococcus tauri.

    Science.gov (United States)

    Le Bihan, Thierry; Hindle, Matthew; Martin, Sarah F; Barrios-Llerena, Martin E; Krahmer, Johanna; Kis, Katalin; Millar, Andrew J; van Ooijen, Gerben

    2015-12-01

    Casein kinase 2 (CK2) is a protein kinase that phosphorylates a plethora of cellular target proteins involved in processes including DNA repair, cell cycle control, and circadian timekeeping. CK2 is functionally conserved across eukaryotes, although the substrate proteins identified in a range of complex tissues are often different. The marine alga Ostreococcus tauri is a unicellular eukaryotic model organism ideally suited to efficiently study generic roles of CK2 in the cellular circadian clock. Overexpression of CK2 leads to a slow circadian rhythm, verifying functional conservation of CK2 in timekeeping. The proteome was analysed in wild-type and CK2-overexpressing algae at dawn and dusk, revealing that differential abundance of the global proteome across the day is largely unaffected by overexpression. However, CK2 activity contributed more strongly to timekeeping at dusk than at dawn. The phosphoproteome of a CK2 overexpression line and cells treated with CK2 inhibitor was therefore analysed and compared to control cells at dusk. We report an extensive catalogue of 447 unique CK2-responsive differential phosphopeptide motifs to inform future studies into CK2 activity in the circadian clock of more complex tissues. All MS data have been deposited in the ProteomeXchange with identifier PXD000975 (http://proteomecentral.proteomexchange.org/dataset/PXD000975). © 2015 The Authors. PROTEOMICS Published by Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  10. The phosphoproteome of toll-like receptor-activated macrophages

    DEFF Research Database (Denmark)

    Weintz, Gabriele; Olsen, Jesper Velgaard; Frühauf, Katja

    2010-01-01

    other signalling modules (e.g. mTOR, ATM/ATR kinases) and the cytoskeleton as hotspots of LPS-regulated phosphorylation. Finally, weaving together phosphoproteome and nascent transcriptome data by in silico promoter analysis, we implicated several phosphorylated TFs in primary LPS-controlled gene...

  11. Strategies for quantitation of phosphoproteomic data

    DEFF Research Database (Denmark)

    Palmisano, Giuseppe; Thingholm, Tine Engberg

    2010-01-01

    Recent developments in phosphoproteomic sample-preparation techniques and sensitive mass spectrometry instrumentation have led to large-scale identifications of phosphoproteins and phosphorylation sites from highly complex samples. This has facilitated the implementation of different quantitation...... will be on different quantitation strategies. Methods for metabolic labeling, chemical modification and label-free quantitation and their applicability or inapplicability in phosphoproteomic studies are discussed....

  12. Benchmarking common quantification strategies for large-scale phosphoproteomics

    DEFF Research Database (Denmark)

    Hogrebe, Alexander; von Stechow, Louise; Bekker-Jensen, Dorte B

    2018-01-01

    Comprehensive mass spectrometry (MS)-based proteomics is now feasible, but reproducible quantification remains challenging, especially for post-translational modifications such as phosphorylation. Here, we compare the most popular quantification techniques for global phosphoproteomics: label......-free quantification (LFQ), stable isotope labeling by amino acids in cell culture (SILAC) and MS2- and MS3-measured tandem mass tags (TMT). In a mixed species comparison with fixed phosphopeptide ratios, we find LFQ and SILAC to be the most accurate techniques. MS2-based TMT yields the highest precision but lowest...... accuracy due to ratio compression, which MS3-based TMT can partly rescue. However, MS2-based TMT outperforms MS3-based TMT when analyzing phosphoproteome changes in the DNA damage response, since its higher precision and larger identification numbers allow detection of a greater number of significantly...

  13. Is phosphoproteomics ready for clinical research?

    Science.gov (United States)

    Iliuk, Anton B; Tao, W Andy

    2013-05-01

    For many diseases such as cancer where phosphorylation-dependent signaling is the foundation of disease onset and progression, single-gene testing and genomic profiling alone are not sufficient in providing most critical information. The reason for this is that in these activated pathways the signaling changes and drug resistance are often not directly correlated with changes in protein expression levels. In order to obtain the essential information needed to evaluate pathway activation or the effects of certain drugs and therapies on the molecular level, the analysis of changes in protein phosphorylation is critical. Existing approaches do not differentiate clinical disease subtypes on the protein and signaling pathway level, and therefore hamper the predictive management of the disease and the selection of therapeutic targets. The mini-review examines the impact of emerging systems biology tools and the possibility of applying phosphoproteomics to clinical research. Copyright © 2012 Elsevier B.V. All rights reserved.

  14. Quantitative phosphoproteomic analysis identifies activation of the RET and IGF-1R/IR signaling pathways in neuroblastoma.

    Directory of Open Access Journals (Sweden)

    Bradley D DeNardo

    Full Text Available Neuroblastoma is an embryonal tumor of childhood with a heterogenous clinical presentation that reflects differences in activation of complex biological signaling pathways. Protein phosphorylation is a key component of cellular signal transduction and plays a critical role in processes that control cancer cell growth and survival. We used shotgun LC/MS to compare phosphorylation between a human MYCN amplified neuroblastoma cell line (NB10, modeling a resistant tumor, and a human neural precursor cell line (NPC, modeling a normal baseline neural crest cell. 2181 unique phosphorylation sites representing 1171 proteins and 2598 phosphopeptides were found. Protein kinases accounted for 6% of the proteome, with a predominance of tyrosine kinases, supporting their prominent role in oncogenic signaling pathways. Highly abundant receptor tyrosine kinase (RTK phosphopeptides in the NB10 cell line relative to the NPC cell line included RET, insulin-like growth factor 1 receptor/insulin receptor (IGF-1R/IR, and fibroblast growth factor receptor 1 (FGFR1. Multiple phosphorylated peptides from downstream mediators of the PI3K/AKT/mTOR and RAS pathways were also highly abundant in NB10 relative to NPC. Our analysis highlights the importance of RET, IGF-1R/IR and FGFR1 as RTKs in neuroblastoma and suggests a methodology that can be used to identify potential novel biological therapeutic targets. Furthermore, application of this previously unexploited technology in the clinic opens the possibility of providing a new wide-scale molecular signature to assess disease progression and prognosis.

  15. Automated Immobilized Metal Affinity Chromatography System for Enrichment of Escherichia coli Phosphoproteome

    Energy Technology Data Exchange (ETDEWEB)

    Qu, Yi; Wu, Si; Zhao, Rui; Zink, Erika M.; Orton, Daniel J.; Moore, Ronald J.; Meng, Da; Clauss, Therese RW; Aldrich, Joshua T.; Lipton, Mary S.; Pasa-Tolic, Ljiljana

    2013-06-05

    Enrichment of bacterial phosphopeptides is an essential step prior to bottom-up mass spectrometry-based analysis of the phosphoproteome, which is fundamental to understanding the role of phosphoproteins in cell signaling and regulation of protein activity. We developed an automated IMAC system to enrich strong cation exchange-fractionated phosphopeptides from the soluble proteome of Escherichia coli MG1655 grown on minimal medium. Initial demonstration of the system resulted in identification of 75 phosphopeptides covering 52 phosphoproteins. Consistent with previous studies, many of these phosphoproteins are involved in the carbohydrate portion of central metabolism. The automated system utilizes a large capacity IMAC column that can effectively enrich phosphopeptides from a bacterial sample by increasing peptide loading and reducing the wash time. An additional benefit of the automated IMAC system is reduced labor and associated costs.

  16. Integration of conventional quantitative and phospho-proteomics reveals new elements in activated Jurkat T-cell receptor pathway maintenance.

    Science.gov (United States)

    Jouy, Florent; Müller, Stephan A; Wagner, Juliane; Otto, Wolfgang; von Bergen, Martin; Tomm, Janina M

    2015-01-01

    Recent years have seen a constant development of tools for the global assessment of phosphoproteins. Here, we outline a concept for integrating approaches for quantitative proteomics and phosphoproteomics. The strategy was applied to the analysis of changes in signalling and protein synthesis occurring after activation of the T-cell receptor (TCR) pathway in a T-cell line (Jurkat cells). For this purpose, peptides were obtained from four biological replicates of activated and control Jurkat T-cells and phosphopeptides enriched via a TiO2-based chromatographic step. Both phosphopeptide-enriched and flow-through fractions were analyzed by LC-MS. We observed 1314 phosphopeptides in the enriched fraction whereas 19 were detected in the flow-through, enabling the quantification of 414 and eight phosphoproteins in the respective fractions. Pathway analysis revealed the differential regulation of many metabolic pathways. Among the quantified proteins, 11 kinases with known TCR-related function were detected. A kinase-substrate database search for the phosphosites identified also confirmed the activity of a further ten kinases. In total, these two approaches provided evidence of 19 unique TCR-related kinases. The combination of phosphoproteomics and conventional quantitative shotgun analysis leads to a more comprehensive assessment of the signalling networks needed for the maintenance of the activated status of Jurkat T-cells. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  17. Characterization of the Phosphoproteome in SLE Patients.

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    Xinzhou Zhang

    Full Text Available Protein phosphorylation is a complex regulatory event that is involved in the signaling networks that affect virtually every cellular process. The protein phosphorylation may be a novel source for discovering biomarkers and drug targets. However, a systematic analysis of the phosphoproteome in patients with SLE has not been performed. To clarify the pathogenesis of systemic lupus erythematosus (SLE, we compared phosphoprotein expression in PBMCs from SLE patients and normal subjects using proteomics analyses. Phosphopeptides were enriched using TiO₂ from PBMCs isolated from 15 SLE patients and 15 healthy subjects and then analyzed by automated LC-MS/MS analysis. Phosphorylation sites were identified and quantitated by MASCOT and MaxQuant. A total of 1035 phosphorylation sites corresponding to 618 NCBI-annotated genes were identified in SLE patients compared with normal subjects. Differentially expressed proteins, peptides and phosphorylation sites were then subjected to bioinformatics analyses. Gene ontology(GO and pathway analyses showed that nucleic acid metabolism, cellular component organization, transport and multicellular organismal development pathways made up the largest proportions of the differentially expressed genes. Pathway analyses showed that the mitogen-activated protein kinase (MAPK signaling pathway and actin cytoskeleton regulators made up the largest proportions of the metabolic pathways. Network analysis showed that rous sarcoma oncogene (SRC, v-rel reticuloendotheliosis viral oncogene homolog A (RELA, histone deacetylase (HDA1C and protein kinase C, delta (PRKCD play important roles in the stability of the network. These data suggest that aberrant protein phosphorylation may contribute to SLE pathogenesis.

  18. Kinase activity ranking using phosphoproteomics data (KARP) quantifies the contribution of protein kinases to the regulation of cell viability.

    Science.gov (United States)

    Wilkes, Edmund H; Casado, Pedro; Rajeeve, Vinothini; Cutillas, Pedro R

    2017-09-01

    Cell survival is regulated by a signaling network driven by the activity of protein kinases; however, determining the contribution that each kinase in the network makes to such regulation remains challenging. Here, we report a computational approach that uses mass spectrometry-based phosphoproteomics data to rank protein kinases based on their contribution to cell regulation. We found that the scores returned by this algorithm, which we have termed kinase activity ranking using phosphoproteomics data (KARP), were a quantitative measure of the contribution that individual kinases make to the signaling output. Application of KARP to the analysis of eight hematological cell lines revealed that cyclin-dependent kinase (CDK) 1/2, casein kinase (CK) 2, extracellular signal-related kinase (ERK), and p21-activated kinase (PAK) were the most frequently highly ranked kinases in these cell models. The patterns of kinase activation were cell-line specific yet showed a significant association with cell viability as a function of kinase inhibitor treatment. Thus, our study exemplifies KARP as an untargeted approach to empirically and systematically identify regulatory kinases within signaling networks. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  19. Phosphoproteomic fingerprinting of epidermal growth factor signaling and anticancer drug action in human tumor cells.

    Science.gov (United States)

    Lim, Yoon-Pin; Diong, Lang-Shi; Qi, Robert; Druker, Brian J; Epstein, Richard J

    2003-12-01

    Many proteins regulating cancer cell growth are tyrosine phosphorylated. Using antiphosphotyrosine affinity chromatography, thiourea protein solubilization, two-dimensional PAGE, and mass spectrometry, we report here the characterization of the epidermal growth factor (EGF)-induced phosphoproteome in A431 human epidermoid carcinoma cells. Using this approach, more than 50 distinct tyrosine phosphoproteins are identifiable within five main clusters-cytoskeletal proteins, signaling enzymes, SH2-containing adaptors, chaperones, and focal adhesion proteins. Comparison of the phosphoproteomes induced in vitro by transforming growth factor-alpha and platelet-derived growth factor demonstrates the pathway- and cell-specific nature of the phosphoproteomes induced. Elimination of both basal and ligand-dependent phosphoproteins by cell exposure to the EGF receptor catalytic inhibitor gefitinib (Iressa, ZD1839) suggests either an autocrine growth loop or the presence of a second inhibited kinase in A431 cells. By identifying distinct patterns of phosphorylation involving novel signaling substrates, and by clarifying the mechanism of action of anticancer drugs, these findings illustrate the potential of immunoaffinity-based phosphoproteomics for guiding the discovery of new drug targets and the rational utilization of pathway-specific chemotherapies.

  20. Proteome and phosphoproteome of primary cultured pig urothelial cells.

    Science.gov (United States)

    Verma, Nisha; Bäuerlein, Carolin; Pink, Mario; Rettenmeier, Albert W; Schmitz-Spanke, Simone

    2011-12-01

    Epithelial tissue lining the inner side of the urinary bladder is the most common target for bladder cancer-related diseases. Bladders of freshly slaughtered pigs were utilised for a comprehensive analysis of the proteome and phosphoproteome of bladder epithelial cells. Following protein separation by 2-D gel electrophoresis and identification by matrix-assisted laser desorption/ionisation time-of-flight mass spectrometry (MALDI-TOF-MS) the first proteome and phosphoproteome maps of pig urinary bladder epithelial cells (PUBEC) were established. A total of 120 selected protein spots were identified. By using the La(3+) enrichment method further developed in our laboratory we identified 31 phosphoproteins with minimal contamination by non-phosphopeptides. The 2-DE map of pig urothelial cells may prove as a useful tool for studies on uroepithelial biology, and the analysed phosphoproteins expression pattern, together with the whole cell proteome, will be helpful for identifying the proteins involved in bladder-related diseases. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  1. Impact of Phosphoproteomics in the Era of Precision Medicine for Prostate Cancer

    Directory of Open Access Journals (Sweden)

    Johnny R. Ramroop

    2018-02-01

    Full Text Available Prostate cancer is the most common malignancy in men in the United States. While androgen deprivation therapy results in tumor responses initially, there is relapse and progression to metastatic castration-resistant prostate cancer. Currently, all prostate cancer patients receive essentially the same treatment, and there is a need for clinically applicable technologies to provide predictive biomarkers toward personalized therapies. Genomic analyses of tumors are used for clinical applications, but with a paucity of obvious driver mutations in metastatic castration-resistant prostate cancer, other applications, such as phosphoproteomics, may complement this approach. Immunohistochemistry and reverse phase protein arrays are limited by the availability of reliable antibodies and evaluates a preselected number of targets. Mass spectrometry-based phosphoproteomics has been used to profile tumors consisting of thousands of phosphopeptides from individual patients after surgical resection or at autopsy. However, this approach is time consuming, and while a large number of candidate phosphopeptides are obtained for evaluation, limitations are reduced reproducibility, sensitivity, and precision. Targeted mass spectrometry can help eliminate these limitations and is more cost effective and less time consuming making it a practical platform for future clinical testing. In this review, we discuss the use of phosphoproteomics in prostate cancer and other clinical cancer tissues for target identification, hypothesis testing, and possible patient stratification. We highlight the majority of studies that have used phosphoproteomics in prostate cancer tissues and cell lines and propose ways forward to apply this approach in basic and clinical research. Overall, the implementation of phosphoproteomics via targeted mass spectrometry has tremendous potential to aid in the development of more rational, personalized therapies that will result in increased survival

  2. Global investigation of interleukin-1β signaling in primary β-cells using quantitative phosphoproteomics

    DEFF Research Database (Denmark)

    Engholm-Keller, Kasper; Størling, Joachim; Pociot, Flemming

    Novel Aspect: Global phosphoproteomic analysis of cytokine signaling in primary β-cells Introduction The insulin-producing β-cells of the pancreatic islets of Langerhans are targeted by aberrant immune system responses in diabetes mellitus involving cytokines, especially interleukin-1β (IL-1 β......), which initiate apoptosis of the β-cells. As only limited amounts of primary β-cells can be isolated from model organisms like mouse and rat, global phosphoproteomic analysis of these signaling events by mass spectrometry has generally been unfeasible. We have therefore developed a strategy...... induced by the cytokine. Preliminary results indicate phosphorylation changes in response to the short-term IL-1β stimulation in for example the calcium/calmodulin-dependent protein kinase type II. This observation is in line with studies using inhibitors of this kinase, implicating it in IL-1β...

  3. SIMAC - A phosphoproteomic strategy for the rapid separation of mono-phosphorylated from multiply phosphorylated peptides

    DEFF Research Database (Denmark)

    Thingholm, Tine E; Jensen, Ole N; Robinson, Phillip J

    2008-01-01

    spectrometric analysis, such as immobilized metal affinity chromatography or titanium dioxide the coverage of the phosphoproteome of a given sample is limited. Here we report a simple and rapid strategy - SIMAC - for sequential separation of mono-phosphorylated peptides and multiply phosphorylated peptides from...... and an optimized titanium dioxide chromatographic method. More than double the total number of identified phosphorylation sites was obtained with SIMAC, primarily from a three-fold increase in recovery of multiply phosphorylated peptides....

  4. Quantitative phosphoproteomics dissection of seven-transmembrane receptor signaling using full and biased agonists

    DEFF Research Database (Denmark)

    Christensen, Gitte L; Kelstrup, Christian D; Lyngsø, Christina

    2010-01-01

    and an important drug target in cardiovascular diseases. "Biased agonists" with intrinsic "functional selectivity" that simultaneously blocks Galpha(q) protein activity and activates G protein-independent pathways of the AT(1)R confer important perspectives in treatment of cardiovascular diseases. In this study......, we performed a global quantitative phosphoproteomics analysis of the AT(1)R signaling network. We analyzed ligand-stimulated SILAC (stable isotope labeling by amino acids in cell culture) cells by high resolution (LTQ-Orbitrap) MS and compared the phosphoproteomes of the AT(1)R agonist angiotensin II...... and the biased agonist [Sar(1),Ile(4),Ile(8)]angiotensin II (SII angiotensin II), which only activates the Galpha(q) protein-independent signaling. We quantified more than 10,000 phosphorylation sites of which 1183 were regulated by angiotensin II or its analogue SII angiotensin II. 36% of the AT(1)R...

  5. Phosphoproteome profiling for cold temperature perception.

    Science.gov (United States)

    Park, Seyeon; Jang, Mi

    2011-02-01

    Temperature sensation initiates from the activation of cellular receptors when the cell is exposed to a decrease in temperature. Here, we applied a phosphoproteome profiling approach to the human lung epithelial cell line BEAS-2B to elucidate cellular cold-responsive processes. The primary aim of this study was to determine which intracellular changes of phosphorylation are accompanied by cold sensation. Eighteen protein spots that exhibited differentially phosphorylated changes in cells were identified. Most of the proteins that were phosphorylated after 5 or 10 min were returned to control levels after 30 or 60 min. Identified proteins were mainly RNA-related (i.e., they were involved in RNA binding and splicing). Temperature (18 and 10°C) stimuli showed homologies that were detected for time course changes in phosphoproteome. The data indicated a time-shift between two temperatures. The phosphorylation of putative cold responsive markers, such as ribosomal protein large P0 and heterochromatin-associated proteins 1, were verified by Western blotting in cells transfected with TRPM8 or TRPA1. Copyright © 2010 Wiley-Liss, Inc.

  6. Large-Scale Phosphoproteomics Reveals Shp-2 Phosphatase-Dependent Regulators of Pdgf Receptor Signaling

    Directory of Open Access Journals (Sweden)

    Tanveer S. Batth

    2018-03-01

    Full Text Available Despite its low cellular abundance, phosphotyrosine (pTyr regulates numerous cell signaling pathways in health and disease. We applied comprehensive phosphoproteomics to unravel differential regulators of receptor tyrosine kinase (RTK-initiated signaling networks upon activation by Pdgf-ββ, Fgf-2, or Igf-1 and identified more than 40,000 phosphorylation sites, including many phosphotyrosine sites without additional enrichment. The analysis revealed RTK-specific regulation of hundreds of pTyr sites on key signaling molecules. We found the tyrosine phosphatase Shp-2 to be the master regulator of Pdgfr pTyr signaling. Application of a recently introduced allosteric Shp-2 inhibitor revealed global regulation of the Pdgf-dependent tyrosine phosphoproteome, which significantly impaired cell migration. In addition, we present a list of hundreds of Shp-2-dependent targets and putative substrates, including Rasa1 and Cortactin with increased pTyr and Gab1 and Erk1/2 with decreased pTyr. Our study demonstrates that large-scale quantitative phosphoproteomics can precisely dissect tightly regulated kinase-phosphatase signaling networks.

  7. Quantitative cardiac phosphoproteomics profiling during ischemia-reperfusion in an immature swine model

    Energy Technology Data Exchange (ETDEWEB)

    Ledee, Dolena R.; Kang, Min A.; Kajimoto, Masaki; Purvine, Samuel O.; Brewer, Heather M.; Pasa Tolic, Ljiljana; Portman, Michael A.

    2017-07-01

    Ischemia-reperfusion (I/R) results in altered metabolic and molecular responses, and phosphorylation is one of the most noted regulatory mechanisms mediating signaling mechanisms during physiological stresses. To expand our knowledge of the potential phosphoproteomic changes in the myocardium during I/R, we used Isobaric Tags for Relative and Absolute Quantitation-based analyses in left ventricular samples obtained from porcine hearts under control or I/R conditions. The data are available via ProteomeXchange with identifier PXD006066. We identified 1,896 phosphopeptides within left ventricular control and I/R porcine samples. Significant differential phosphorylation between control and I/R groups was discovered in 111 phosphopeptides from 86 proteins. Analysis of the phosphopeptides using Motif-x identified five motifs: (..R..S..), (..SP..), (..S.S..), (..S…S..), and (..S.T..). Semiquantitative immunoblots confirmed site location and directional changes in phosphorylation for phospholamban and pyruvate dehydrogenase E1, two proteins known to be altered by I/R and identified by this study. Novel phosphorylation sites associated with I/R were also identified. Functional characterization of the phosphopeptides identified by our methodology could expand our understanding of the signaling mechanisms involved during I/R damage in the heart as well as identify new areas to target therapeutic strategies.

  8. Quantitative phosphoproteomic analysis of postmortem muscle development

    DEFF Research Database (Denmark)

    Huang, Honggang

    and myofibrillar proteins from PM porcine muscle. Generally, the porcine muscle with fast pH decline rate had the highest phosphorylation level at 1 h PM, but lowest at 24 h PM, whereas the group with slow pH decline rate showed the reverse case. The protein phosphorylation level of sarcoplasmic proteins...

  9. Systems Analysis for Interpretation of Phosphoproteomics Data

    DEFF Research Database (Denmark)

    Munk, Stephanie; Refsgaard, Jan C; Olsen, Jesper V

    2016-01-01

    provides the best means for extracting functional insights from such types of datasets, and this has primed a rapid development of bioinformatics tools and resources over the last decade. Many of these tools are specialized databases that can be mined for annotation and pathway enrichment, whereas others...

  10. Off-Line High-pH Reversed-Phase Fractionation for In-Depth Phosphoproteomics

    DEFF Research Database (Denmark)

    Batth, Tanveer S; Francavilla, Chiara; Olsen, Jesper V

    2014-01-01

    H) before subsequent titanium dioxide (TiO2) enrichment and LC-MS/MS analysis. Our results demonstrate that HpH is superior to standard strong-cation exchange (SCX) fractionation in the total number of phosphopeptides detected when analyzing the same number of fractions by identical LC-MS/MS gradients. From...... phosphorylated peptides over that with SCX. Further optimizations in the pooling and concatenation strategy increased the total number of multiphosphorylated peptides detected after HpH fractionation. In conclusion, we provide a basic framework and resource for performing in-depth phosphoproteome studies...

  11. TiO2-Based Phosphoproteomic Analysis of the Plasma Membrane and the Effects of Phosphatase Inhibitor Treatment

    DEFF Research Database (Denmark)

    Thingholm, Tine; Larsen, Martin Røssel; Ingrell, Christian

    2008-01-01

    . We used sucrose centrifugation in combination with sodium carbonate extraction to achieve efficient and reproducible purification of low microgram levels of plasma membrane proteins from human mesenchymal stem cells (hMSCs, 10 (7) cells), achieving more than 70% yield of membrane proteins....... Phosphopeptide enrichment by titanium dioxide chromatography followed by capillary liquid chromatography-tandem mass spectrometry allowed us to assign 703 unique phosphorylation sites in 376 phosphoproteins. Our experiments revealed that treatment of cell cultures with three different types of protein...

  12. Phosphoproteome and transcription factor activity profiling identify actions of the anti-inflammatory agent UTL-5g in LPS stimulated RAW 264.7 cells including disrupting actin remodeling and STAT-3 activation.

    Science.gov (United States)

    Carruthers, Nicholas J; Stemmer, Paul M; Chen, Ben; Valeriote, Frederick; Gao, Xiaohua; Guatam, Subhash C; Shaw, Jiajiu

    2017-09-15

    UTL-5g is a novel small-molecule TNF-alpha modulator. It reduces cisplatin-induced side effects by protecting kidney, liver, and platelets, thereby increasing tolerance for cisplatin. UTL-5g also reduces radiation-induced acute liver toxicity. The mechanism of action for UTL-5g is not clear at the present time. A phosphoproteomic analysis to a depth of 4943 phosphopeptides and a luminescence-based transcription factor activity assay were used to provide complementary analyses of signaling events that were disrupted by UTL-5g in RAW 264.7 cells. Transcriptional activity downstream of the interferon gamma, IL-6, type 1 Interferon, TGF-β, PKC/Ca 2+ and the glucocorticoid receptor pathways were disrupted by UTL-5g. Phosphoproteomic analysis indicated that hyperphosphorylation of proteins involved in actin remodeling was suppressed by UTL-5g (gene set analysis, FDR 5g. This global characterization of UTL-5g activity in a macrophage cell line discovered that it disrupts selected aspects of LPS signaling including Stat3 activation and actin remodeling providing new insight on how UTL-5g acts to reduce cisplatin-induced side effects. Copyright © 2017 Elsevier B.V. All rights reserved.

  13. Phosphoproteome profiling provides insight into the mechanism of action for carvedilol-mediated cancer prevention.

    Science.gov (United States)

    Cleveland, Kristan H; Yeung, Steven; Huang, Kevin M; Liang, Sherry; Andresen, Bradley T; Huang, Ying

    2018-04-06

    Recent studies suggest that the β-blocker drug carvedilol prevents skin carcinogenesis but the mechanism is unknown. Carvedilol is one of a few β-blockers identified as biased agonist based on an ability to promote β-arrestin-mediated processes such as ERK phosphorylation. To understand the role of phosphoproteomic signaling in carvedilol's anticancer activity, the mouse epidermal JB6 P+ cells treated with EGF, carvedilol or their combination were analyzed using the Phospho Explorer Antibody Array containing 1318 site-specific and phospho-specific antibodies of over 30 signaling pathways. The array data indicated that both EGF and carvedilol increased phosphorylation of ERK's cytosolic target P70S6K while its nuclear target ELK-1 were activated only by EGF; Furthermore, EGF-induced phosphorylation of ELK-1 and c-Jun was attenuated by carvedilol. Subcellular fractionation analysis indicated that ERK nuclear translocation induced by EGF was blocked by co-treatment with carvedilol. Western blot and luciferase reporter assays confirmed that the biased β-blockers carvedilol and alprenolol blocked EGF-induced phosphorylation and activation of c-Jun/AP-1 and ELK-1. Consistently, both carvedilol and alprenolol strongly prevented EGF-induced neoplastic transformation of JB6 P+ cells. Remarkably, oral carvedilol treatment significantly inhibited the growth of A375 melanoma xenograft in SCID mice. Since nuclear translocation of ERK is a key step in carcinogenesis, inhibition of this event is proposed as a novel anticancer mechanism for biased β-blockers such as carvedilol. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  14. Selection of an Appropriate Protein Extraction Method to Study the Phosphoproteome of Maize Photosynthetic Tissue.

    Directory of Open Access Journals (Sweden)

    Inês M Luís

    Full Text Available Often plant tissues are recalcitrant and, due to that, methods relying on protein precipitation, such as TCA/acetone precipitation and phenol extraction, are usually the methods of choice for protein extraction in plant proteomic studies. However, the addition of precipitation steps to protein extraction methods may negatively impact protein recovery, due to problems associated with protein re-solubilization. Moreover, we show that when working with non-recalcitrant plant tissues, such as young maize leaves, protein extraction methods with precipitation steps compromise the maintenance of some labile post-translational modifications (PTMs, such as phosphorylation. Therefore, a critical issue when studying PTMs in plant proteins is to ensure that the protein extraction method is the most appropriate, both at qualitative and quantitative levels. In this work, we compared five methods for protein extraction of the C4-photosynthesis related proteins, in the tip of fully expanded third-leaves. These included: TCA/Acetone Precipitation; Phenol Extraction; TCA/Acetone Precipitation followed by Phenol Extraction; direct extraction in Lysis Buffer (a urea-based buffer; and direct extraction in Lysis Buffer followed by Cleanup with a commercial kit. Protein extraction in Lysis Buffer performed better in comparison to the other methods. It gave one of the highest protein yields, good coverage of the extracted proteome and phosphoproteome, high reproducibility, and little protein degradation. This was also the easiest and fastest method, warranting minimal sample handling. We also show that this method is adequate for the successful extraction of key enzymes of the C4-photosynthetic metabolism, such as PEPC, PPDK, PEPCK, and NADP-ME. This was confirmed by MALDI-TOF/TOF MS analysis of excised spots of 2DE analyses of the extracted protein pools. Staining for phosphorylated proteins in 2DE revealed the presence of several phosphorylated isoforms of PEPC, PPDK

  15. Dissection of the insulin signaling pathway via quantitative phosphoproteomics

    DEFF Research Database (Denmark)

    Krüger, Marcus; Kratchmarova, Irina; Blagoev, Blagoy

    2008-01-01

    spectrum of the tyrosine phosphorylation cascade, we have defined the tyrosine-phosphoproteome of the insulin signaling pathway, using high resolution mass spectrometry in combination with phosphotyrosine immunoprecipitation and stable isotope labeling by amino acids in cell culture (SILAC......The insulin signaling pathway is of pivotal importance in metabolic diseases, such as diabetes, and in cellular processes, such as aging. Insulin activates a tyrosine phosphorylation cascade that branches to create a complex network affecting multiple biological processes. To understand the full...

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

    Science.gov (United States)

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

    2010-02-05

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

  17. A quantitative map of the liver mitochondrial phosphoproteome reveals post-translational control of ketogenesis

    Science.gov (United States)

    Grimsrud, Paul A.; Carson, Joshua J.; Hebert, Alex S.; Hubler, Shane L.; Niemi, Natalie M.; Bailey, Derek J.; Jochem, Adam; Stapleton, Donald S.; Keller, Mark P.; Westphall, Michael S.; Yandell, Brian S.; Attie, Alan D.; Coon, Joshua J.; Pagliarini, David J.

    2012-01-01

    Summary Mitochondria are dynamic organelles that play a central role in a diverse array of metabolic processes. Elucidating mitochondrial adaptations to changing metabolic demands and the pathogenic alterations that underlie metabolic disorders represent principal challenges in cell biology. Here, we performed multiplexed quantitative mass spectrometry-based proteomics to chart the remodeling of the mouse liver mitochondrial proteome and phosphoproteome during both acute and chronic physiological transformations in more than 50 mice. Our analyses reveal that reversible phosphorylation is widespread in mitochondria, and is a key mechanism for regulating ketogenesis during the onset of obesity and type 2 diabetes. Specifically, we have demonstrated that phosphorylation of a conserved serine on Hmgcs2 (S456) significantly enhances its catalytic activity in response to increased ketogenic demand. Collectively, our work describes the plasticity of this organelle at high resolution and provides a framework for investigating the roles of proteome restructuring and reversible phosphorylation in mitochondrial adaptation. PMID:23140645

  18. Parallel reaction monitoring on a Q Exactive mass spectrometer increases reproducibility of phosphopeptide detection in bacterial phosphoproteomics measurements.

    Science.gov (United States)

    Taumer, Christoph; Griesbaum, Lena; Kovacevic, Alen; Soufi, Boumediene; Nalpas, Nicolas C; Macek, Boris

    2018-03-29

    Increasing number of studies report the relevance of protein Ser/Thr/Tyr phosphorylation in bacterial physiology, yet the analysis of this type of modification in bacteria still presents a considerable challenge. Unlike in eukaryotes, where tens of thousands of phosphorylation events likely occupy more than two thirds of the proteome, the abundance of protein phosphorylation is much lower in bacteria. Even the state-of-the-art phosphopeptide enrichment protocols fail to remove the high background of abundant unmodified peptides, leading to low signal intensity and undersampling of phosphopeptide precursor ions in consecutive data-dependent MS runs. Consequently, large-scale bacterial phosphoproteomic datasets often suffer from poor reproducibility and a high number of missing values. Here we explore the application of parallel reaction monitoring (PRM) on a Q Exactive mass spectrometer in bacterial phosphoproteome analysis, focusing especially on run-to-run sampling reproducibility. In multiple measurements of identical phosphopeptide-enriched samples, we show that PRM outperforms data-dependent acquisition (DDA) in terms of detection frequency, reaching almost complete sampling efficiency, compared to 20% in DDA. We observe a similar trend over multiple heterogeneous phosphopeptide-enriched samples and conclude that PRM shows a great promise in bacterial phosphoproteomics analyses where reproducible detection and quantification of a relatively small set of phosphopeptides is desired. Bacterial phosphorylated peptides occur in low abundance compared to their unmodified counterparts, and are therefore rarely reproducibly detected in shotgun (DDA) proteomics measurements. Here we show that parallel reaction monitoring complements DDA analyses and makes detection of known, targeted phosphopeptides more reproducible. This will be of significance in replicated MS measurements that have a goal to reproducibly detect and quantify phosphopeptides of interest. Copyright

  19. Unraveling Kinase Activation Dynamics Using Kinase-Substrate Relationships from Temporal Large-Scale Phosphoproteomics Studies.

    Science.gov (United States)

    Domanova, Westa; Krycer, James; Chaudhuri, Rima; Yang, Pengyi; Vafaee, Fatemeh; Fazakerley, Daniel; Humphrey, Sean; James, David; Kuncic, Zdenka

    2016-01-01

    In response to stimuli, biological processes are tightly controlled by dynamic cellular signaling mechanisms. Reversible protein phosphorylation occurs on rapid time-scales (milliseconds to seconds), making it an ideal carrier of these signals. Advances in mass spectrometry-based proteomics have led to the identification of many tens of thousands of phosphorylation sites, yet for the majority of these the kinase is unknown and the underlying network topology of signaling networks therefore remains obscured. Identifying kinase substrate relationships (KSRs) is therefore an important goal in cell signaling research. Existing consensus sequence motif based prediction algorithms do not consider the biological context of KSRs, and are therefore insensitive to many other mechanisms guiding kinase-substrate recognition in cellular contexts. Here, we use temporal information to identify biologically relevant KSRs from Large-scale In Vivo Experiments (KSR-LIVE) in a data-dependent and automated fashion. First, we used available phosphorylation databases to construct a repository of existing experimentally-predicted KSRs. For each kinase in this database, we used time-resolved phosphoproteomics data to examine how its substrates changed in phosphorylation over time. Although substrates for a particular kinase clustered together, they often exhibited a different temporal pattern to the phosphorylation of the kinase. Therefore, although phosphorylation regulates kinase activity, our findings imply that substrate phosphorylation likely serve as a better proxy for kinase activity than kinase phosphorylation. KSR-LIVE can thereby infer which kinases are regulated within a biological context. Moreover, KSR-LIVE can also be used to automatically generate positive training sets for the subsequent prediction of novel KSRs using machine learning approaches. We demonstrate that this approach can distinguish between Akt and Rps6kb1, two kinases that share the same linear consensus motif

  20. Unraveling Kinase Activation Dynamics Using Kinase-Substrate Relationships from Temporal Large-Scale Phosphoproteomics Studies.

    Directory of Open Access Journals (Sweden)

    Westa Domanova

    Full Text Available In response to stimuli, biological processes are tightly controlled by dynamic cellular signaling mechanisms. Reversible protein phosphorylation occurs on rapid time-scales (milliseconds to seconds, making it an ideal carrier of these signals. Advances in mass spectrometry-based proteomics have led to the identification of many tens of thousands of phosphorylation sites, yet for the majority of these the kinase is unknown and the underlying network topology of signaling networks therefore remains obscured. Identifying kinase substrate relationships (KSRs is therefore an important goal in cell signaling research. Existing consensus sequence motif based prediction algorithms do not consider the biological context of KSRs, and are therefore insensitive to many other mechanisms guiding kinase-substrate recognition in cellular contexts. Here, we use temporal information to identify biologically relevant KSRs from Large-scale In Vivo Experiments (KSR-LIVE in a data-dependent and automated fashion. First, we used available phosphorylation databases to construct a repository of existing experimentally-predicted KSRs. For each kinase in this database, we used time-resolved phosphoproteomics data to examine how its substrates changed in phosphorylation over time. Although substrates for a particular kinase clustered together, they often exhibited a different temporal pattern to the phosphorylation of the kinase. Therefore, although phosphorylation regulates kinase activity, our findings imply that substrate phosphorylation likely serve as a better proxy for kinase activity than kinase phosphorylation. KSR-LIVE can thereby infer which kinases are regulated within a biological context. Moreover, KSR-LIVE can also be used to automatically generate positive training sets for the subsequent prediction of novel KSRs using machine learning approaches. We demonstrate that this approach can distinguish between Akt and Rps6kb1, two kinases that share the same

  1. Celiac anti-type 2 transglutaminase antibodies induce phosphoproteome modification in intestinal epithelial Caco-2 cells.

    Directory of Open Access Journals (Sweden)

    Gaetana Paolella

    Full Text Available BACKGROUND: Celiac disease is an inflammatory condition of the small intestine that affects genetically predisposed individuals after dietary wheat gliadin ingestion. Type 2-transglutaminase (TG2 activity seems to be responsible for a strong autoimmune response in celiac disease, TG2 being the main autoantigen. Several studies support the concept that celiac anti-TG2 antibodies may contribute to disease pathogenesis. Our recent findings on the ability of anti-TG2 antibodies to induce a rapid intracellular mobilization of calcium ions, as well as extracellular signal-regulated kinase phosphorylation, suggest that they potentially act as signaling molecules. In line with this concept, we have investigated whether anti-TG2 antibodies can induce phosphoproteome modification in an intestinal epithelial cell line. METHODS AND PRINCIPAL FINDINGS: We studied phosphoproteome modification in Caco-2 cells treated with recombinant celiac anti-TG2 antibodies. We performed a two-dimensional electrophoresis followed by specific staining of phosphoproteins and mass spectrometry analysis of differentially phosphorylated proteins. Of 14 identified proteins (excluding two uncharacterized proteins, three were hypophosphorylated and nine were hyperphosphorylated. Bioinformatics analyses confirmed the presence of phosphorylation sites in all the identified proteins and highlighted their involvement in several fundamental biological processes, such as cell cycle progression, cell stress response, cytoskeletal organization and apoptosis. CONCLUSIONS: Identification of differentially phosphorylated proteins downstream of TG2-antibody stimulation suggests that in Caco-2 cells these antibodies perturb cell homeostasis by behaving as signaling molecules. We hypothesize that anti-TG2 autoantibodies may destabilize the integrity of the intestinal mucosa in celiac individuals, thus contributing to celiac disease establishment and progression. Since several proteins here

  2. Phosphoproteome Profiling of Human Skin Fibroplast Cells in Response to Low- and High-Dose Irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Yang, Feng; Stenoien, David L.; Strittmatter, Eric F.; Wang, Jeng-Han; Ding, Lianghao; Lipton, Mary S.; Monroe, Matthew E.; Nicora, Carrie D.; Gritsenko, Marina A.; Tang, Keqi; Fang, Ruihua; Adkins, Joshua N.; Camp, David G.; Chen, David J.; Smith, Richard D.

    2006-05-01

    The biological effect of low-dose radiation is currently not well understood. A hallmark of the response to radiation is the phosphorylation of proteins involved in DNA repair, DNA damage signaling, and cell cycle checkpoint control, which is important in prompt cellular response. The objective of the work presented here was to explore the phosphoproteome of normal human skin fibroblast (HSF) cells to reveal differences between low- and high-dose irradiation responses at the protein phosphorylation level. Several techniques —Trizol extract of proteins, methylation of the enzyme digest (peptides), enrichment of phosphopeptides with immobilized metal affinity chromatography (IMAC), nanoflow reversed-phase HPLC (nano-LC)/electrospray ionization, and tandem mass spectrometry— were combined for analysis of the HSF cell phosphoproteome following low- and high-doses of irradiation. More than 95% of the peptides identified after IMAC enrichment were phosphopeptides. Among the 493 unique phosphopeptides, 232 were singly phosphorylated, 220 were doubly phosphorylated, and 41 were triply phosphorylated, indicating the overall effectiveness of the IMAC technique to enrich both singly and multiple phosphorylated peptides. Over 700 phosphorylation sites were assigned to a total of 346 proteins, many of which are known or proposed to be highly relevant to a plethora of fundamental biological processes. The profile for proteins identified from the low-dose (2cGy) irradiated HSF cells was shown to be different from the profile obtained for proteins irradiated at the high-dose (4 Gy). This type of fundamental information regarding radiation-response to cellular events at the molecular level provides a mechanistic basis for identifying relevant molecular markers that can be used in future to better evaluate human health risks at low doses of irradiation and to develop low dose radiation counter measurements.

  3. Phosphoproteomic profiling of human myocardial tissues distinguishes ischemic from non-ischemic end stage heart failure.

    Directory of Open Access Journals (Sweden)

    Matthew A Schechter

    Full Text Available The molecular differences between ischemic (IF and non-ischemic (NIF heart failure are poorly defined. A better understanding of the molecular differences between these two heart failure etiologies may lead to the development of more effective heart failure therapeutics. In this study extensive proteomic and phosphoproteomic profiles of myocardial tissue from patients diagnosed with IF or NIF were assembled and compared. Proteins extracted from left ventricular sections were proteolyzed and phosphopeptides were enriched using titanium dioxide resin. Gel- and label-free nanoscale capillary liquid chromatography coupled to high resolution accuracy mass tandem mass spectrometry allowed for the quantification of 4,436 peptides (corresponding to 450 proteins and 823 phosphopeptides (corresponding to 400 proteins from the unenriched and phospho-enriched fractions, respectively. Protein abundance did not distinguish NIF from IF. In contrast, 37 peptides (corresponding to 26 proteins exhibited a ≥ 2-fold alteration in phosphorylation state (p<0.05 when comparing IF and NIF. The degree of protein phosphorylation at these 37 sites was specifically dependent upon the heart failure etiology examined. Proteins exhibiting phosphorylation alterations were grouped into functional categories: transcriptional activation/RNA processing; cytoskeleton structure/function; molecular chaperones; cell adhesion/signaling; apoptosis; and energetic/metabolism. Phosphoproteomic analysis demonstrated profound post-translational differences in proteins that are involved in multiple cellular processes between different heart failure phenotypes. Understanding the roles these phosphorylation alterations play in the development of NIF and IF has the potential to generate etiology-specific heart failure therapeutics, which could be more effective than current therapeutics in addressing the growing concern of heart failure.

  4. Quantitative proteomics and phosphoproteomics of sugar beet monosomic addition line M14 in response to salt stress.

    Science.gov (United States)

    Yu, Bing; Li, Jinna; Koh, Jin; Dufresne, Craig; Yang, Na; Qi, Shishi; Zhang, Yongxue; Ma, Chunquan; Duong, Benjamin V; Chen, Sixue; Li, Haiying

    2016-06-30

    Salinity is a major abiotic stress affecting plant growth, development and agriculture productivity. Understanding the molecular mechanisms of salt stress tolerance will provide valuable information for effective crop engineering and breeding. Sugar beet monosomic addition line M14 obtained from the intercross between Beta vulgaris L. and Beta corolliflora Zoss exhibits tolerance to salt stress. In this study, the changes in the M14 proteome and phosphoproteome induced by salt stress were analyzed. We report the characteristics of the M14 plants under 0, 200, and 400mM NaCl using label-free quantitative proteomics approaches. Protein samples were subjected to total proteome profiling using LC-MS/MS and phosphopeptide enrichment to identify phosphopeptides and phosphoproteins. A total of 2182 proteins were identified and 114 proteins showed differential levels under salt stress. Interestingly, 189 phosphoproteins exhibited significant changes at the phosphorylation level under salt stress. Several signaling components associated with salt stress were found, e.g. 14-3-3 and mitogen-activated protein kinases (MAPK). Fifteen differential phosphoproteins and proteins involved in signal transduction were tested at the transcriptional level. The results revealed the short-term salt responsive mechanisms of the special sugar beet M14 line using label-free quantitative phosphoproteomics. Sugar beet monosomic addition line M14 is a special germplasm with salt stress tolerance. Analysis of the M14 proteome and phosphoproteome under salt stress has provided insight into specific response mechanisms underlying salt stress tolerance. Reversible protein phosphorylation regulates a wide range of cellular processes such as transmembrane signaling, intracellular amplification of signals, and cell-cycle control. This study has identified significantly changed proteins and phosphoproteins, and determined their potential relevance to salt stress response. The knowledge gained can be

  5. The current state of the art of quantitative phosphoproteomics and its applications to diabetes research

    Energy Technology Data Exchange (ETDEWEB)

    Chan, Chi Yuet X’avia; Gritsenko, Marina A.; Smith, Richard D.; Qian, Wei-Jun

    2016-03-17

    Protein phosphorylation is a fundamental regulatory mechanism in many cellular processes and aberrant perturbation of phosphorylation has been revealed in various human diseases. Kinases and their cognate inhibitors have been hotspot for drug development. Therefore, the emerging tools, which enable a system-wide quantitative profiling of phosphoproteome, would offer a powerful impetus in unveiling novel signaling pathways, drug targets and/or biomarkers for the disease of interest. In this review, we will highlight recent advances in phosphoproteomics, the current state-of-the-art of the technologies, and the challenges and future perspectives of this research area. Finally, we will underscore some exemplary applications of phosphoproteomics in diabetes research.

  6. Multiplexed detection of O-GlcNAcome, phosphoproteome and whole proteome within the same gel

    Directory of Open Access Journals (Sweden)

    Caroline eCieniewski-Bernard

    2014-10-01

    Full Text Available The cellular diversity of proteins results in part from their post-translational modifications. Among all of them, the O-GlcNAcylation is an atypical glycosylation, more similar to phosphorylation than classical glycosylations. Highly dynamic, reversible, and exclusively localized on cytosolic, nuclear and mitochondrial proteins, O-GlcNAcylation is known to regulate almost all if not all cellular processes. Fundamental for the cell life, O-GlcNAcylation abnormalities are involved in the etiology of several inherited diseases. Assessing to O-GlcNAcylation pattern will permit to get relevant data about the role of O-GlcNAcylation in cell physiology. To get understanding about the role of O-GlcNAcylation, as also considering its interplay with phosphorylation, the O-GlcNAc profiling remains a real challenge for the community of proteomists/glycoproteomists. Due to development of multiplexed proteomics based on fluorescent detection of proteins, there is growing body of evidence about the proteome knowledge’s. We propose herein a multiplexed proteomic strategy to detect O-GlcNAcylated proteins, phosphoproteins, and the whole proteome within the same bidimensional gel. In particular, we investigated the phosphoproteome through the ProQ Diamond staining, while the whole proteome was visualized through Sypro Ruby staining, or after the labeling of proteins with a T-Dye fluorophore. The O-GlcNAcome was revealed by the way of the Click chemistry and the azide-alkyne cycloaddition of a fluorophore on GlcNAc moieties. This method permits, after sequential image acquisition, the direct in-gel detection of O-GlcNAcome, phosphoproteome and whole proteome.

  7. Evidence for a Minimal Eukaryotic Phosphoproteome?

    NARCIS (Netherlands)

    Diks, Sander H.; Parikh, Kaushal; van der Sijde, Marijke; Joore, Jos; Ritsema, Tita; Peppelenbosch, Maikel P.

    2007-01-01

    Background. Reversible phosphorylation catalysed by kinases is probably the most important regulatory mechanism in eukaryotes. Methodology/Principal Findings. We studied the in vitro phosphorylation of peptide arrays exhibiting the majority of PhosphoBase-deposited protein sequences, by factors in

  8. Implications of tyrosine phosphoproteomics in cervical carcinogenesis

    Directory of Open Access Journals (Sweden)

    DeFord James

    2008-01-01

    Full Text Available Abstract Background Worldwide cervical cancer remains a leading cause of mortality from gynecologic malignancies. The link between cervical cancer and persistent infection with HPV has been established. At a molecular level little is known about the transition from the precancerous state to invasive cancer. To elucidate this process, cervical biopsies from human specimens were obtained from precancerous state to stage III disease. Methods Cervical biopsies were obtained from patients with a diagnosis of cervical cancer undergoing definitive surgery or staging operation. Biopsies were obtained from patients with precancerous lesions at the time of their excisional procedure. Control samples were obtained from patients undergoing hysterectomy for benign conditions such as fibroids. Samples were subjected to proteomic profiling using two dimensional gel electrophoresis with subsequent trypsin digestion followed by MALDI-TOF protein identification. Candidate proteins were then further studied using western blotting, immunoprecipitation and immunohistochemistry. Results Annexin A1 and DNA-PKcs were found to be differentially expressed. Phosphorylated annexin A1 was up regulated in diseased states in comparison to control and its level was strongly detected in the serum of cervical cancer patients compared to controls. DNA-PKcs was noted to be hyperphosphorylated and fragmented in cancer when compared to controls. By immunohistochemistry annexin A1 was noted in the vascular environment in cancer and certain precancerous samples. Conclusion This study suggests a probable role for protein tyrosine phosphorylation in cervical carcinogenesis. Annexin A1 and DNA-PK cs may have synergistic effects with HPV infection. Precancerous lesions that may progress to cervical cancer may be differentiated from lesions that will not base on similar immunohistochemical profile to invasive squamous cell carcinoma.

  9. Nuclear phosphoproteome of developing chickpea seedlings (Cicer arietinum L.) and protein-kinase interaction network.

    Science.gov (United States)

    Kumar, Rajiv; Kumar, Amit; Subba, Pratigya; Gayali, Saurabh; Barua, Pragya; Chakraborty, Subhra; Chakraborty, Niranjan

    2014-06-13

    Nucleus, the control centre of eukaryotic cell, houses most of the genetic machineries required for gene expression and their regulation. Post translational modifications of proteins, particularly phosphorylation control a wide variety of cellular processes but its functional connectivity, in plants, is still elusive. This study profiled the nuclear phosphoproteome of a grain legume, chickpea, to gain better understanding of such event. Intact nuclei were isolated from 3-week-old seedlings using two independent methods, and nuclear proteins were resolved by 2-DE. In a separate set of experiments, phosphoproteins were enriched using IMAC method and resolved by 1-DE. The separated proteins were stained with phosphospecific Pro-Q Diamond stain. Proteomic analyses led to the identification of 107 putative phosphoproteins, of which 86 were non-redundant. Multiple sites of phosphorylation were predicted on several key elements, which included both regulatory and functional proteins. The analysis revealed an array of phosphoproteins, presumably involved in a variety of cellular functions, viz., protein folding (24%), signalling and gene regulation (22%), DNA replication, repair and modification (16%), and metabolism (13%), among others. These results represent the first nucleus-specific phosphoproteome map of a non-model legume, which would provide insights into the possible function of protein phosphorylation in plants. Chickpea is grown over 10 million hectares of land worldwide, and global production hovers around 8.5 million metric tons annually. Despite its nutritional merits, it is often referred to as 'orphan' legume and has remained outside the realm of large-scale functional genomics studies. While current chickpea genome initiative has primarily focused on sequence information and functional annotation, proteomics analyses are limited. It is thus important to study the proteome of the cell organelle particularly the nucleus, which harbors most of the genetic

  10. Phosphoproteomic dynamics of chickpea (Cicer arietinum L.) reveals shared and distinct components of dehydration response.

    Science.gov (United States)

    Subba, Pratigya; Barua, Pragya; Kumar, Rajiv; Datta, Asis; Soni, Kamlesh Kumar; Chakraborty, Subhra; Chakraborty, Niranjan

    2013-11-01

    Reversible protein phosphorylation is a ubiquitous regulatory mechanism that plays critical roles in transducing stress signals to bring about coordinated intracellular responses. To gain better understanding of dehydration response in plants, we have developed a differential phosphoproteome in a food legume, chickpea (Cicer arietinum L.). Three-week-old chickpea seedlings were subjected to progressive dehydration by withdrawing water, and the changes in the phosphorylation status of a large repertoire of proteins were monitored. The proteins were resolved by 2-DE and stained with phosphospecific fluorescent Pro-Q Diamond dye. Mass spectrometric analysis led to the identification of 91 putative phosphoproteins, presumably involved in a variety of functions including cell defense and rescue, photosynthesis and photorespiration, molecular chaperones, and ion transport, among others. Multiple sites of phosphorylation were predicted on several key elements, which include both the regulatory as well as the functional proteins. A critical survey of the phosphorylome revealed a DREPP (developmentally regulated plasma membrane protein) plasma membrane polypeptide family protein, henceforth designated CaDREPP1. The transcripts of CaDREPP1 were found to be differentially regulated under dehydration stress, further corroborating the proteomic results. This work provides new insights into the possible phosphorylation events triggered by the conditions of progressive water-deficit in plants.

  11. Quantitative Proteomic and Phosphoproteomic Approaches for Deciphering the Signaling Pathway for Tension Wood Formation in Poplar.

    Science.gov (United States)

    Mauriat, Mélanie; Leplé, Jean-Charles; Claverol, Stéphane; Bartholomé, Jérôme; Negroni, Luc; Richet, Nicolas; Lalanne, Céline; Bonneu, Marc; Coutand, Catherine; Plomion, Christophe

    2015-08-07

    Trees adjust their growth following forced changes in orientation to re-establish a vertical position. In angiosperms, this adjustment involves the differential regulation of vascular cambial activity between the lower (opposite wood) and upper (tension wood) sides of the leaning stem. We investigated the molecular mechanisms leading to the formation of differential wood types through a quantitative proteomic and phosphoproteomic analysis on poplar subjected to a gravitropic stimulus. We identified and quantified 675 phosphopeptides, corresponding to 468 phosphoproteins, and 3 763 nonphosphorylated peptides, corresponding to 1 155 proteins, in the differentiating xylem of straight-growing trees (control) and trees subjected to a gravitational stimulus during 8 weeks. About 1% of the peptides were specific to a wood type (straight, opposite, or tension wood). Proteins quantified in more than one type of wood were more numerous: a mixed linear model showed 389 phosphopeptides and 556 proteins to differ in abundance between tension wood and opposite wood. Twenty-one percent of the phosphoproteins identified here were described in their phosphorylated form for the first time. Our analyses revealed remarkable developmental molecular plasticity, with wood type-specific phosphorylation events, and highlighted the involvement of different proteins in the biosynthesis of cell wall components during the formation of the three types of wood.

  12. Comparative Proteome and Phosphoproteome Analyses during Cyprid Development of the Barnacle Balanus ( =Amphibalanus ) amphitrite

    KAUST Repository

    Zhang, Yu

    2010-06-04

    The barnacle Balanus amphitrite (=Amphibalanus amphitrite) is a major marine biofouling invertebrate worldwide. It has a complex life cycle during which the larva (called a nauplius) molts six times before transforming into the cyprid stage. The cyprid stage in B. amphitrite is the critical stage for the larval decision to attach and metamorphose. In this study, proteome and phosphoproteome alterations during cyprid development/aging and upon treatment with the antifouling agent butenolide were examined with a two-dimensional electrophoresis (2-DE) multiplexed fluorescent staining approach. Optimized protein separation strategies, including solution-phase isoelectric fractionation and narrow-pH-range 2-DE, were used in a proteomic analysis. Our results show that the differential regulation of the target proteins is highly dynamic on the levels of both protein expression and posttranslational modification. Two groups of proteins, stress-associated and energy metabolism-related proteins, are differentially expressed during cyprid development. Comparison of the control and treatment groups suggests that butenolide exerts its effects by sustaining the expression levels of these proteins. Altogether, our data suggest that proteins involved in stress regulation and energy metabolism play crucial roles in regulating larval attachment and metamorphosis of B. amphitrite. © 2010 American Chemical Society.

  13. Battle through signaling between wheat and the fungal pathogen Septoria tritici revealed by proteomics and phosphoproteomics

    DEFF Research Database (Denmark)

    Yang, Fen; Braga, Marcella Nunes de Melo; Larsen, Martin Røssel

    2013-01-01

    accumulation of signal molecules, including calcium, H2O2, NO, and sugars, in the resistant than in the susceptible cultivar in response to the infection. Additionally, 31 proteins and 5 phosphoproteins from the pathogen were identified, including metabolic proteins and signaling proteins such as GTP-binding...... proteins, 14-3-3 proteins, and calcium-binding proteins. Quantitative PCR analysis showed the expression of fungal signaling genes and genes encoding a superoxide dismutase and cell-wall degrading enzymes. These results indicate roles of signaling, antioxidative stress mechanisms, and nutrient acquisition...... resulting in a multiple-level activation of transcription and translation processes of defense responses. Our sensitive approaches and model provide a comprehensive (phospho)proteomics resource for studying signaling from the point of view of both host and pathogen during a plant-pathogen interaction....

  14. Targeted mass spectrometry: An emerging powerful approach to unblock the bottleneck in phosphoproteomics.

    Science.gov (United States)

    Osinalde, Nerea; Aloria, Kerman; Omaetxebarria, Miren J; Kratchmarova, Irina

    2017-06-15

    Following the rapid expansion of the proteomics field, the investigation of post translational modifications (PTM) has become extremely popular changing our perspective of how proteins constantly fine tune cellular functions. Reversible protein phosphorylation plays a pivotal role in virtually all biological processes in the cell and it is one the most characterized PTM up to date. During the last decade, the development of phosphoprotein/phosphopeptide enrichment strategies and mass spectrometry (MS) technology has revolutionized the field of phosphoproteomics discovering thousands of new site-specific phosphorylations and unveiling unprecedented evidence about their modulation under distinct cellular conditions. The field has expanded so rapidly that the use of traditional methods to validate and characterize the biological role of the phosphosites is not feasible any longer. Targeted MS holds great promise for becoming the method of choice to study with high precision and sensitivity already known site-specific phosphorylation events. This review summarizes the contribution of large-scale unbiased MS analyses and highlights the need of targeted MS-based approaches for follow-up investigation. Additionally, the article illustrates the biological relevance of protein phosphorylation by providing examples of disease-related phosphorylation events and emphasizes the benefits of applying targeted MS in clinics for disease diagnosis, prognosis and drug-response evaluation. Copyright © 2017 Elsevier B.V. All rights reserved.

  15. A quantitative map of the liver mitochondrial phosphoproteome reveals posttranslational control of ketogenesis.

    Science.gov (United States)

    Grimsrud, Paul A; Carson, Joshua J; Hebert, Alex S; Hubler, Shane L; Niemi, Natalie M; Bailey, Derek J; Jochem, Adam; Stapleton, Donald S; Keller, Mark P; Westphall, Michael S; Yandell, Brian S; Attie, Alan D; Coon, Joshua J; Pagliarini, David J

    2012-11-07

    Mitochondria are dynamic organelles that play a central role in a diverse array of metabolic processes. Elucidating mitochondrial adaptations to changing metabolic demands and the pathogenic alterations that underlie metabolic disorders represent principal challenges in cell biology. Here, we performed multiplexed quantitative mass spectrometry-based proteomics to chart the remodeling of the mouse liver mitochondrial proteome and phosphoproteome during both acute and chronic physiological transformations in more than 50 mice. Our analyses reveal that reversible phosphorylation is widespread in mitochondria, and is a key mechanism for regulating ketogenesis during the onset of obesity and type 2 diabetes. Specifically, we have demonstrated that phosphorylation of a conserved serine on Hmgcs2 (S456) significantly enhances its catalytic activity in response to increased ketogenic demand. Collectively, our work describes the plasticity of this organelle at high resolution and provides a framework for investigating the roles of proteome restructuring and reversible phosphorylation in mitochondrial adaptation. Copyright © 2012 Elsevier Inc. All rights reserved.

  16. Proteomic Analysis to Identify Functional Molecules in Drug Resistance Caused by E-Cadherin Knockdown in 3D-Cultured Colorectal Cancer Models

    Science.gov (United States)

    2013-09-01

    methods and developed a new method for phosphoproteomic studies, which was published in Journal of Proteome Research. In conclusion, during the...19) Zhai, B.; Villen, J.; Beausoleil, S. A.; Mintseris, J.; Gygi, S. P. Phosphoproteome analysis of Drosophila melanogaster embryos . J. Proteome ...P a g e | 1 AD_________________ Award Number: W81XWH-12-1-0412 TITLE: Proteomic Analysis to

  17. TiSH--a robust and sensitive global phosphoproteomics strategy employing a combination of TiO2, SIMAC, and HILIC

    DEFF Research Database (Denmark)

    Engholm-Keller, Kasper; Birck, Pernille; Størling, Joachim

    2012-01-01

    -phosphorylated peptides, and hydrophilic interaction liquid chromatography (HILIC) of the mono-phosphorylated peptides (collectively abbreviated "TiSH"). The advantages of the strategy include a high specificity and sample preparation workload reduction due to the TiO(2) pre-enrichment step, as well as low adsorptive......, with an enrichment specificity>94%. When doing network analysis of putative phosphorylation changes it could be noted that the identified protein interaction network centered upon proteins known to be affected by the interferon-¿ pathway, thereby supporting the utility of this global phosphoproteomics strategy...

  18. Proteome and phosphoproteome characterization reveals new response and defense mechanisms of Brachypodium distachyon leaves under salt stress.

    Science.gov (United States)

    Lv, Dong-Wen; Subburaj, Saminathan; Cao, Min; Yan, Xing; Li, Xiaohui; Appels, Rudi; Sun, Dong-Fa; Ma, Wujun; Yan, Yue-Ming

    2014-02-01

    Salinity is a major abiotic stress affecting plant growth and development. Understanding the molecular mechanisms of salt response and defense in plants will help in efforts to improve the salt tolerance of crops. Brachypodium distachyon is a new model plant for wheat, barley, and several potential biofuel grasses. In the current study, proteome and phosphoproteome changes induced by salt stress were the focus. The Bd21 leaves were initially treated with salt in concentrations ranging from 80 to 320 mm and then underwent a recovery process prior to proteome analysis. A total of 80 differentially expressed protein spots corresponding to 60 unique proteins were identified. The sample treated with a median salt level of 240 mm and the control were selected for phosphopeptide purification using TiO2 microcolumns and LC-MS/MS for phosphoproteome analysis to identify the phosphorylation sites and phosphoproteins. A total of 1509 phosphoproteins and 2839 phosphorylation sites were identified. Among them, 468 phosphoproteins containing 496 phosphorylation sites demonstrated significant changes at the phosphorylation level. Nine phosphorylation motifs were extracted from the 496 phosphorylation sites. Of the 60 unique differentially expressed proteins, 14 were also identified as phosphoproteins. Many proteins and phosphoproteins, as well as potential signal pathways associated with salt response and defense, were found, including three 14-3-3s (GF14A, GF14B, and 14-3-3A) for signal transduction and several ABA signal-associated proteins such as ABF2, TRAB1, and SAPK8. Finally, a schematic salt response and defense mechanism in B. distachyon was proposed.

  19. Nuclear Phosphoproteomic Screen Uncovers ACLY as Mediator of IL-2-induced Proliferation of CD4+ T lymphocytes

    DEFF Research Database (Denmark)

    Osinalde, Nerea; Mitxelena, Jone; Sánchez-Quiles, Virginia

    2016-01-01

    that are not clearly understood. To study the role of IL-2 in the regulation of nuclear protein function we have performed an unbiased mass spectrometry-based study of the nuclear phosphoproteome of resting and IL-2-treated CD4(+) T lymphocytes. We detected 8521distinct phosphosites including many that are not yet......Anti-cancer immunotherapies commonly rely on the use of interleukin-2 (IL-2) to promote the expansion of T lymphocytes. IL-2- dependent proliferation is the culmination of a complex network of phosphorylation-driven signaling events that impact on gene transcription through mechanisms...... reported in curated phosphorylation databases. Although most phosphorylation sites remained unaffected upon IL-2 treatment, 391 sites corresponding to 288 gene products showed robust IL-2-dependent regulation. Importantly, we show that ATP-citrate lyase (ACLY) is a key phosphoprotein effector of IL-2...

  20. Phosphoproteomic profiling of in vivo signaling in liver by the mammalian target of rapamycin complex 1 (mTORC1.

    Directory of Open Access Journals (Sweden)

    Gokhan Demirkan

    Full Text Available Our understanding of signal transduction networks in the physiological context of an organism remains limited, partly due to the technical challenge of identifying serine/threonine phosphorylated peptides from complex tissue samples. In the present study, we focused on signaling through the mammalian target of rapamycin (mTOR complex 1 (mTORC1, which is at the center of a nutrient- and growth factor-responsive cell signaling network. Though studied extensively, the mechanisms involved in many mTORC1 biological functions remain poorly understood.We developed a phosphoproteomic strategy to purify, enrich and identify phosphopeptides from rat liver homogenates. Using the anticancer drug rapamycin, the only known target of which is mTORC1, we characterized signaling in liver from rats in which the complex was maximally activated by refeeding following 48 hr of starvation. Using protein and peptide fractionation methods, TiO(2 affinity purification of phosphopeptides and mass spectrometry, we reproducibly identified and quantified over four thousand phosphopeptides. Along with 5 known rapamycin-sensitive phosphorylation events, we identified 62 new rapamycin-responsive candidate phosphorylation sites. Among these were PRAS40, gephyrin, and AMP kinase 2. We observed similar proportions of increased and reduced phosphorylation in response to rapamycin. Gene ontology analysis revealed over-representation of mTOR pathway components among rapamycin-sensitive phosphopeptide candidates.In addition to identifying potential new mTORC1-mediated phosphorylation events, and providing information relevant to the biology of this signaling network, our experimental and analytical approaches indicate the feasibility of large-scale phosphoproteomic profiling of tissue samples to study physiological signaling events in vivo.

  1. Phosphoproteomics Reveals MAPK Inhibitors Enhance MET- and EGFR-Driven AKT Signaling in KRAS-Mutant Lung Cancer.

    Science.gov (United States)

    Kim, Jae-Young; Welsh, Eric A; Fang, Bin; Bai, Yun; Kinose, Fumi; Eschrich, Steven A; Koomen, John M; Haura, Eric B

    2016-10-01

    Pathway inhibition of the RAS-driven MAPK pathway using small-molecule kinase inhibitors has been a key focus for treating cancers driven by oncogenic RAS, yet significant clinical responses are lacking. Feedback reactivation of ERK driven by drug-induced RAF activity has been suggested as one of the major drug resistance mechanisms, especially in the context of oncogenic RAS. To determine whether additional adaptive resistance mechanisms may coexist, we characterized global phosphoproteomic changes after MEK inhibitor selumetinib (AZD6244) treatment in KRAS-mutant A427 and A549 lung adenocarcinoma cell lines employing mass spectrometry-based phosphoproteomics. We identified 9,075 quantifiable unique phosphosites (corresponding to 3,346 unique phosphoproteins), of which 567 phosphosites were more abundant and 512 phosphosites were less abundant after MEK inhibition. Selumetinib increased phosphorylation of KSR-1, a scaffolding protein required for assembly of MAPK signaling complex, as well as altered phosphorylation of GEF-H1, a novel regulator of KSR-1 and implicated in RAS-driven MAPK activation. Moreover, selumetinib reduced inhibitory serine phosphorylation of MET at Ser985 and potentiated HGF- and EGF-induced AKT phosphorylation. These results were recapitulated by pan-RAF (LY3009120), MEK (GDC0623), and ERK (SCH772984) inhibitors, which are currently under early-phase clinical development against RAS-mutant cancers. Our results highlight the unique adaptive changes in MAPK scaffolding proteins (KSR-1, GEF-H1) and in RTK signaling, leading to enhanced PI3K-AKT signaling when the MAPK pathway is inhibited. This study highlights the unique adaptive changes in MAPK scaffolding proteins (KSR-1, GEF-H1) and in RTK signaling, leading to enhanced PI3K/AKT signaling when the MAPK pathway is inhibited. Mol Cancer Res; 14(10); 1019-29. ©2016 AACR. ©2016 American Association for Cancer Research.

  2. Large-Scale Phosphoproteomics Reveals Shp-2 Phosphatase-Dependent Regulators of Pdgf Receptor Signaling

    DEFF Research Database (Denmark)

    Batth, Tanveer S; Papetti, Moreno; Pfeiffer, Anamarija

    2018-01-01

    of Pdgfr pTyr signaling. Application of a recently introduced allosteric Shp-2 inhibitor revealed global regulation of the Pdgf-dependent tyrosine phosphoproteome, which significantly impaired cell migration. In addition, we present a list of hundreds of Shp-2-dependent targets and putative substrates...

  3. Enhanced Phosphoproteomic Profiling Workflow For Growth Factor Signaling Analysis

    DEFF Research Database (Denmark)

    Sylvester, Marc; Burbridge, Mike; Leclerc, Gregory

    2010-01-01

    A549 lung carcinoma cells were used as a model and stimulated with hepatocyte growth factor, epidermal growth factor or fibroblast growth factor. We employed a quick protein digestion workflow with spin filters without using urea. Phosphopeptides in general were enriched by sequential elution from...... transfer dissociation adds confidence in modification site assignment. The workflow is relatively simple but the integration of complementary techniques leads to a deeper insight into cellular signaling networks and the potential pharmacological intervention thereof....

  4. Analysis of protein phosphorylation using mass spectrometry: deciphering the phosphoproteome

    DEFF Research Database (Denmark)

    Mann, Matthias; Ong, Shao En; Grønborg, Mads

    2002-01-01

    In signal transduction in eukaryotes, protein phosphorylation is a key event. To understand signaling processes, we must first acquire an inventory of phosphoproteins and their phosphorylation sites under different conditions. Because phosphorylation is a dynamic process, elucidation of signaling...

  5. Identifying Drug Effects via Pathway Alterations using an Integer Linear Programming Optimization Formulation on Phosphoproteomic Data

    Science.gov (United States)

    Mitsos, Alexander; Melas, Ioannis N.; Siminelakis, Paraskeuas; Chairakaki, Aikaterini D.; Saez-Rodriguez, Julio; Alexopoulos, Leonidas G.

    2009-01-01

    Understanding the mechanisms of cell function and drug action is a major endeavor in the pharmaceutical industry. Drug effects are governed by the intrinsic properties of the drug (i.e., selectivity and potency) and the specific signaling transduction network of the host (i.e., normal vs. diseased cells). Here, we describe an unbiased, phosphoproteomic-based approach to identify drug effects by monitoring drug-induced topology alterations. With our proposed method, drug effects are investigated under diverse stimulations of the signaling network. Starting with a generic pathway made of logical gates, we build a cell-type specific map by constraining it to fit 13 key phopshoprotein signals under 55 experimental conditions. Fitting is performed via an Integer Linear Program (ILP) formulation and solution by standard ILP solvers; a procedure that drastically outperforms previous fitting schemes. Then, knowing the cell's topology, we monitor the same key phosphoprotein signals under the presence of drug and we re-optimize the specific map to reveal drug-induced topology alterations. To prove our case, we make a topology for the hepatocytic cell-line HepG2 and we evaluate the effects of 4 drugs: 3 selective inhibitors for the Epidermal Growth Factor Receptor (EGFR) and a non-selective drug. We confirm effects easily predictable from the drugs' main target (i.e., EGFR inhibitors blocks the EGFR pathway) but we also uncover unanticipated effects due to either drug promiscuity or the cell's specific topology. An interesting finding is that the selective EGFR inhibitor Gefitinib inhibits signaling downstream the Interleukin-1alpha (IL1α) pathway; an effect that cannot be extracted from binding affinity-based approaches. Our method represents an unbiased approach to identify drug effects on small to medium size pathways which is scalable to larger topologies with any type of signaling interventions (small molecules, RNAi, etc). The method can reveal drug effects on pathways

  6. Salt-induced changes in cardiac phosphoproteome in a rat model of chronic renal failure.

    Directory of Open Access Journals (Sweden)

    Zhengxiu Su

    Full Text Available Heart damage is widely present in patients with chronic kidney disease. Salt diet is the most important environmental factor affecting development of chronic renal failure and cardiovascular diseases. The proteins involved in chronic kidney disease -induced heart damage, especially their posttranslational modifications, remain largely unknown to date. Sprague-Dawley rats underwent 5/6 nephrectomy (chronic renal failure model or sham operation were treated for 2 weeks with a normal-(0.4% NaCl, or high-salt (4% NaCl diet. We employed TiO2 enrichment, iTRAQ labeling and liquid-chromatography tandem mass spectrometry strategy for phosphoproteomic profiling of left ventricular free walls in these animals. A total of 1724 unique phosphopeptides representing 2551 non-redundant phosphorylation sites corresponding to 763 phosphoproteins were identified. During normal salt feeding, 89 (54% phosphopeptides upregulated and 76 (46% phosphopeptides downregulated in chronic renal failure rats relative to sham rats. In chronic renal failure rats, high salt intake induced upregulation of 84 (49% phosphopeptides and downregulation of 88 (51% phosphopeptides. Database searches revealed that most of the identified phospholproteins were important signaling molecules such as protein kinases, receptors and phosphatases. These phospholproteins were involved in energy metabolism, cell communication, cell differentiation, cell death and other biological processes. The Search Tool for the Retrieval of Interacting Genes analysis revealed functional links among 15 significantly regulated phosphoproteins in chronic renal failure rats compared to sham group, and 23 altered phosphoproteins induced by high salt intake. The altered phosphorylation levels of two proteins involved in heart damage, lamin A and phospholamban were validated. Expression of the downstream genes of these two proteins, desmin and SERCA2a, were also analyzed.

  7. Identification of BCAP-{sub L} as a negative regulator of the TLR signaling-induced production of IL-6 and IL-10 in macrophages by tyrosine phosphoproteomics

    Energy Technology Data Exchange (ETDEWEB)

    Matsumura, Takayuki [Consolidated Research Institute for Advanced Science and Medical Care, Waseda University, Shinjuku-ku, Tokyo 162-0041 (Japan); Department of Life Science and Medical Bio-Science, Waseda University, Shinjuku-ku, Tokyo 162-8480 (Japan); Oyama, Masaaki; Kozuka-Hata, Hiroko [Medical Proteomics Laboratory, Institute of Medical Science, University of Tokyo, Minato-ku, Tokyo 108-8639 (Japan); Ishikawa, Kosuke; Inoue, Takafumi [Consolidated Research Institute for Advanced Science and Medical Care, Waseda University, Shinjuku-ku, Tokyo 162-0041 (Japan); Department of Life Science and Medical Bio-Science, Waseda University, Shinjuku-ku, Tokyo 162-8480 (Japan); Muta, Tatsushi [Laboratory of Cell Recognition and Response, Graduate School of Life Sciences, Tohoku University, Sendai 980-8578 (Japan); Semba, Kentaro, E-mail: ksemba@waseda.jp [Consolidated Research Institute for Advanced Science and Medical Care, Waseda University, Shinjuku-ku, Tokyo 162-0041 (Japan); Department of Life Science and Medical Bio-Science, Waseda University, Shinjuku-ku, Tokyo 162-8480 (Japan); Inoue, Jun-ichiro, E-mail: jun-i@ims.u-tokyo.ac.jp [Medical Proteomics Laboratory, Institute of Medical Science, University of Tokyo, Minato-ku, Tokyo 108-8639 (Japan); Division of Cellular and Molecular Biology, Institute of Medical Science, University of Tokyo, Minato-ku, Tokyo 108-8639 (Japan)

    2010-09-17

    Research highlights: {yields} Twenty five tyrosine-phosphorylated proteins in LPS-stimulated macrophages were determined. {yields} BCAP is a novel tyrosine-phosphorylated protein in LPS-stimulated macrophages. {yields} BCAP-{sub L} inhibits IL-6 and IL-10 production in LPS-stimulated macrophages. -- Abstract: Toll-like receptor (TLR) signaling in macrophages is essential for anti-pathogen responses such as cytokine production and antigen presentation. Although numerous reports suggest that protein tyrosine kinases (PTKs) are involved in cytokine induction in response to lipopolysaccharides (LPS; TLR4 ligand) in macrophages, the PTK-mediated signal transduction pathway has yet to be analyzed in detail. Here, we carried out a comprehensive and quantitative dynamic tyrosine phosphoproteomic analysis on the TLR4-mediated host defense system in RAW264.7 macrophages using stable isotope labeling by amino acids in cell culture (SILAC). We determined the temporal profiles of 25 proteins based on SILAC-encoded peptide(s). Of these, we focused on the tyrosine phosphorylation of B-cell adaptor for phosphatidylinositol 3-kinase (BCAP) because the function of BCAP remains unknown in TLR signaling in macrophages. Furthermore, Bcap has two distinct transcripts, a full-length (Bcap-{sub L}) and an alternatively initiated or spliced (Bcap-{sub S}) mRNA, and little is known about the differential functions of the BCAP-{sub L} and BCAP-{sub S} proteins. Our study showed, for the first time, that RNAi-mediated selective depletion of BCAP-{sub L} enhanced IL-6 and IL-10 production but not TNF-{alpha} production in TLR ligand-stimulated macrophages. We propose that BCAP-{sub L} (but not BCAP-{sub S}) is a negative regulator of the TLR-mediated host defense system in macrophages.

  8. Hippocampal phosphoproteomics of F344 rats exposed to 1-bromopropane

    Energy Technology Data Exchange (ETDEWEB)

    Huang, Zhenlie [Guangdong Provincial Key Laboratory of Occupational Disease Prevention and Treatment, Guangdong Province Hospital for Occupational Disease Prevention and Treatment, Guangzhou 510-300 (China); Department of Occupational and Environmental Health, Nagoya University Graduate School of Medicine, Nagoya 466-8550 (Japan); Ichihara, Sahoko [Graduate School of Regional Innovation Studies, Mie University, Tsu 514-8507 (Japan); Oikawa, Shinji [Department of Environmental and Molecular Medicine, Mie University Graduate School of Medicine, Mie 514-8507 (Japan); Chang, Jie [Department of Occupational and Environmental Health, Nagoya University Graduate School of Medicine, Nagoya 466-8550 (Japan); Graduate School of Regional Innovation Studies, Mie University, Tsu 514-8507 (Japan); Zhang, Lingyi [Department of Occupational and Environmental Health, Nagoya University Graduate School of Medicine, Nagoya 466-8550 (Japan); Department of Occupational and Environmental Health, Faculty of Pharmaceutical Sciences, Tokyo University of Science, Noda 278-8510 (Japan); Hu, Shijie [Guangdong Provincial Key Laboratory of Occupational Disease Prevention and Treatment, Guangdong Province Hospital for Occupational Disease Prevention and Treatment, Guangzhou 510-300 (China); Huang, Hanlin, E-mail: huanghl@gdoh.org [Guangdong Provincial Key Laboratory of Occupational Disease Prevention and Treatment, Guangdong Province Hospital for Occupational Disease Prevention and Treatment, Guangzhou 510-300 (China); Ichihara, Gaku, E-mail: gak@rs.tus.ac.jp [Department of Occupational and Environmental Health, Nagoya University Graduate School of Medicine, Nagoya 466-8550 (Japan); Department of Occupational and Environmental Health, Faculty of Pharmaceutical Sciences, Tokyo University of Science, Noda 278-8510 (Japan)

    2015-01-15

    1-Bromopropane (1-BP) is neurotoxic in both experimental animals and human. To identify phosphorylated modification on the unrecognized post-translational modifications of proteins and investigate their role in 1-BP-induced neurotoxicity, changes in hippocampal phosphoprotein expression levels were analyzed quantitatively in male F344 rats exposed to 1-BP inhalation at 0, 400, or 1000 ppm for 8 h/day for 1 or 4 weeks. Hippocampal protein extracts were analyzed qualitatively and quantitatively by Pro-Q Diamond gel staining and SYPRO Ruby staining coupled with two-dimensional difference in gel electrophoresis (2D-DIGE), respectively, as well as by matrix-assisted laser-desorption ionization time-of-flight (MALDI-TOF) mass spectrometry (MS) to identify phosphoproteins. Changes in selected proteins were further confirmed by Manganese II (Mn{sup 2+})-Phos-tag SDS-polyacrylamide gel electrophoresis (SDS-PAGE). Bax and cytochrome c protein levels were determined by western blotting. Pro-Q Diamond gel staining combined with 2D-DIGE identified 26 phosphoprotein spots (p < 0.05), and MALDI-TOF/MS identified 18 up-regulated proteins and 8 down-regulated proteins. These proteins are involved in the biological process of response to stimuli, metabolic processes, and apoptosis signaling. Changes in the expression of phosphorylated 14-3-3 θ were further confirmed by Mn{sup 2+}-Phos-tag SDS-PAGE. Western blotting showed overexpression of Bax protein in the mitochondria with down-regulation in the cytoplasm, whereas cytochrome c expression was high in the cytoplasm but low in the mitochondria after 1-BP exposure. Our results suggest that the pathogenesis of 1-BP-induced hippocampal damage involves inhibition of antiapoptosis process. Phosphoproteins identified in this study can potentially serve as biomarkers for 1-BP-induced neurotoxicity. - Highlights: • 1-BP modified hippocampal phosphoproteome in rat and 23 altered proteins were identified. • 1-BP changed phosphorylation

  9. Phosphoproteome of the cyanobacterium Synechocystis sp. PCC 6803 and its dynamics during nitrogen starvation.

    Directory of Open Access Journals (Sweden)

    Philipp eSpät

    2015-03-01

    Full Text Available Cyanobacteria have shaped the earth’s biosphere as the first oxygenic photoautotrophs and still play an important role in many ecosystems. The ability to adapt to changing environmental conditions is an essential characteristic in order to ensure survival. To this end, numerous studies have shown that bacteria use protein post-translational modifications such as Ser/Thr/Tyr phosphorylation in cell signalling, adaptation and regulation. Nevertheless, our knowledge of cyanobacterial phosphoproteomes and their dynamic response to environmental stimuli is relatively limited. In this study, we applied gel-free methods and high accuracy mass spectrometry towards the unbiased detection of Ser/Thr/Tyr phosphorylation events in the model cyanobacterium Synechocystis sp. PCC 6803. We could identify over 300 phosphorylation events in cultures grown on nitrate as exclusive nitrogen source. Chemical dimethylation labelling was applied to investigate proteome and phosphoproteome dynamics during nitrogen starvation. Our dataset describes the most comprehensive (phosphoproteome of Synechocystis to date, identifying 2,382 proteins and 183 phosphorylation events and quantifying 2,111 proteins and 148 phosphorylation events during nitrogen starvation. Global protein phosphorylation levels were increased in response to nitrogen depletion after 24 hours. Among the proteins with increased phosphorylation, the PII signalling protein showed the highest fold-change, serving as positive control. Other proteins with increased phosphorylation levels comprised functions in photosynthesis and in carbon and nitrogen metabolism. This study reveals dynamics of Synechocystis phosphoproteome in response to environmental stimuli and suggests an important role of protein Ser/Thr/Tyr phosphorylation in fundamental mechanisms of homeostatic control in cyanobacteria.

  10. Comparative Phosphoproteomics Reveals an Important Role of MKK2 in Banana (Musa spp.) Cold Signal Network.

    Science.gov (United States)

    Gao, Jie; Zhang, Sheng; He, Wei-Di; Shao, Xiu-Hong; Li, Chun-Yu; Wei, Yue-Rong; Deng, Gui-Ming; Kuang, Rui-Bin; Hu, Chun-Hua; Yi, Gan-Jun; Yang, Qiao-Song

    2017-01-20

    Low temperature is one of the key environmental stresses, which greatly affects global banana production. However, little is known about the global phosphoproteomes in Musa spp. and their regulatory roles in response to cold stress. In this study, we conducted a comparative phosphoproteomic profiling of cold-sensitive Cavendish Banana and relatively cold tolerant Dajiao under cold stress. Phosphopeptide abundances of five phosphoproteins involved in MKK2 interaction network, including MKK2, HY5, CaSR, STN7 and kinesin-like protein, show a remarkable difference between Cavendish Banana and Dajiao in response to cold stress. Western blotting of MKK2 protein and its T31 phosphorylated peptide verified the phosphoproteomic results of increased T31 phosphopeptide abundance with decreased MKK2 abundance in Daojiao for a time course of cold stress. Meanwhile increased expression of MKK2 with no detectable T31 phosphorylation was found in Cavendish Banana. These results suggest that the MKK2 pathway in Dajiao, along with other cold-specific phosphoproteins, appears to be associated with the molecular mechanisms of high tolerance to cold stress in Dajiao. The results also provide new evidence that the signaling pathway of cellular MKK2 phosphorylation plays an important role in abiotic stress tolerance that likely serves as a universal plant cold tolerance mechanism.

  11. Comparative Phosphoproteomics Reveals an Important Role of MKK2 in Banana (Musa spp.) Cold Signal Network

    Science.gov (United States)

    Gao, Jie; Zhang, Sheng; He, Wei-Di; Shao, Xiu-Hong; Li, Chun-Yu; Wei, Yue-Rong; Deng, Gui-Ming; Kuang, Rui-Bin; Hu, Chun-Hua; Yi, Gan-Jun; Yang, Qiao-Song

    2017-01-01

    Low temperature is one of the key environmental stresses, which greatly affects global banana production. However, little is known about the global phosphoproteomes in Musa spp. and their regulatory roles in response to cold stress. In this study, we conducted a comparative phosphoproteomic profiling of cold-sensitive Cavendish Banana and relatively cold tolerant Dajiao under cold stress. Phosphopeptide abundances of five phosphoproteins involved in MKK2 interaction network, including MKK2, HY5, CaSR, STN7 and kinesin-like protein, show a remarkable difference between Cavendish Banana and Dajiao in response to cold stress. Western blotting of MKK2 protein and its T31 phosphorylated peptide verified the phosphoproteomic results of increased T31 phosphopeptide abundance with decreased MKK2 abundance in Daojiao for a time course of cold stress. Meanwhile increased expression of MKK2 with no detectable T31 phosphorylation was found in Cavendish Banana. These results suggest that the MKK2 pathway in Dajiao, along with other cold-specific phosphoproteins, appears to be associated with the molecular mechanisms of high tolerance to cold stress in Dajiao. The results also provide new evidence that the signaling pathway of cellular MKK2 phosphorylation plays an important role in abiotic stress tolerance that likely serves as a universal plant cold tolerance mechanism. PMID:28106078

  12. The Tec Kinase-Regulated Phosphoproteome Reveals a Mechanism for the Regulation of Inhibitory Signals in Murine Macrophages.

    Science.gov (United States)

    Tampella, Giacomo; Kerns, Hannah M; Niu, Deqiang; Singh, Swati; Khim, Socheath; Bosch, Katherine A; Garrett, Meghan E; Moguche, Albanus; Evans, Erica; Browning, Beth; Jahan, Tahmina A; Nacht, Mariana; Wolf-Yadlin, Alejandro; Plebani, Alessandro; Hamerman, Jessica A; Rawlings, David J; James, Richard G

    2015-07-01

    Previous work has shown conflicting roles for Tec family kinases in regulation of TLR-dependent signaling in myeloid cells. In the present study, we performed a detailed investigation of the role of the Tec kinases Btk and Tec kinases in regulating TLR signaling in several types of primary murine macrophages. We demonstrate that primary resident peritoneal macrophages deficient for Btk and Tec secrete less proinflammatory cytokines in response to TLR stimulation than do wild-type cells. In contrast, we found that bone marrow-derived and thioglycollate-elicited peritoneal macrophages deficient for Btk and Tec secrete more proinflammatory cytokines than do wild-type cells. We then compared the phosphoproteome regulated by Tec kinases and LPS in primary peritoneal and bone marrow-derived macrophages. From this analysis we determined that Tec kinases regulate different signaling programs in these cell types. In additional studies using bone marrow-derived macrophages, we found that Tec and Btk promote phosphorylation events necessary for immunoreceptor-mediated inhibition of TLR signaling. Taken together, our results are consistent with a model where Tec kinases (Btk, Tec, Bmx) are required for TLR-dependent signaling in many types of myeloid cells. However, our data also support a cell type-specific TLR inhibitory role for Btk and Tec that is mediated by immunoreceptor activation and signaling via PI3K. Copyright © 2015 by The American Association of Immunologists, Inc.

  13. Identification of novel protein functions and signaling mechanisms by genetics and quantitative phosphoproteomics in Caenorhabditis elegans

    DEFF Research Database (Denmark)

    Fredens, Julius; Engholm-Keller, Kasper; Møller-Jensen, Jakob

    2014-01-01

    knockdown by feeding the nematode on pre-labeled lysine auxotroph Escherichia coli. In this chapter, we describe in details the generation of the E. coli strain, incorporation of heavy isotope-labeled lysine in C. elegans, and the procedure for a comprehensive global phosphoproteomic experiment.......Stable isotope labeling by amino acids combined with mass spectrometry is a widely used methodology for measuring relative changes in protein and phosphorylation levels at a global level. We have applied this method to the model organism Caenorhabditis elegans in combination with RNAi-mediated gene...

  14. System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation

    DEFF Research Database (Denmark)

    Rigbolt, Kristoffer T G; Prokhorova, Tatyana A; Akimov, Vyacheslav

    2011-01-01

    To elucidate cellular events underlying the pluripotency of human embryonic stem cells (hESCs), we performed parallel quantitative proteomic and phosphoproteomic analyses of hESCs during differentiation initiated by a diacylglycerol analog or transfer to media that had not been conditioned...... by feeder cells. We profiled 6521 proteins and 23,522 phosphorylation sites, of which almost 50% displayed dynamic changes in phosphorylation status during 24 hours of differentiation. These data are a resource for studies of the events associated with the maintenance of hESC pluripotency and those...

  15. IKAP: A heuristic framework for inference of kinase activities from Phosphoproteomics data.

    Science.gov (United States)

    Mischnik, Marcel; Sacco, Francesca; Cox, Jürgen; Schneider, Hans-Christoph; Schäfer, Matthias; Hendlich, Manfred; Crowther, Daniel; Mann, Matthias; Klabunde, Thomas

    2016-02-01

    Phosphoproteomics measurements are widely applied in cellular biology to detect changes in signalling dynamics. However, due to the inherent complexity of phosphorylation patterns and the lack of knowledge on how phosphorylations are related to functions, it is often not possible to directly deduce protein activities from those measurements. Here, we present a heuristic machine learning algorithm that infers the activities of kinases from Phosphoproteomics data using kinase-target information from the PhosphoSitePlus database. By comparing the estimated kinase activity profiles to the measured phosphosite profiles, it is furthermore possible to derive the kinases that are most likely to phosphorylate the respective phosphosite. We apply our approach to published datasets of the human cell cycle generated from HeLaS3 cells, and insulin signalling dynamics in mouse hepatocytes. In the first case, we estimate the activities of 118 at six cell cycle stages and derive 94 new kinase-phosphosite links that can be validated through either database or motif information. In the second case, the activities of 143 kinases at eight time points are estimated and 49 new kinase-target links are derived. The algorithm is implemented in Matlab and be downloaded from github. It makes use of the Optimization and Statistics toolboxes. https://github.com/marcel-mischnik/IKAP.git. marcel.mischnik@gmail.com Supplementary data are available at Bioinformatics online. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  16. Proteomic and phosphoproteomic analyses of chromatin-associated proteins from Arabidopsis thaliana

    KAUST Repository

    Bigeard, Jean

    2014-07-10

    The nucleus is the organelle where basically all DNA-related processes take place in eukaryotes, such as replication, transcription, and splicing as well as epigenetic regulation. The identification and description of the nuclear proteins is one of the requisites toward a comprehensive understanding of the biological functions accomplished in the nucleus. Many of the regulatory mechanisms of protein functions rely on their PTMs among which phosphorylation is probably one of the most important properties affecting enzymatic activity, interaction with other molecules, localization, or stability. So far, the nuclear and subnuclear proteome and phosphoproteome of the model plant Arabidopsis thaliana have been the subject of very few studies. In this work, we developed a purification protocol of Arabidopsis chromatin-associated proteins and performed proteomic and phosphoproteomic analyses identifying a total of 879 proteins of which 198 were phosphoproteins that were mainly involved in chromatin remodeling, transcriptional regulation, and RNA processing. From 230 precisely localized phosphorylation sites (phosphosites), 52 correspond to hitherto unidentified sites. This protocol and data thereby obtained should be a valuable resource for many domains of plant research.

  17. Cardiac Phosphoproteomics during Remote Ischemic Preconditioning: A Role for the Sarcomeric Z-Disk Proteins

    Directory of Open Access Journals (Sweden)

    Safa Abdul-Ghani

    2014-01-01

    Full Text Available Remote ischemic preconditioning (RIPC induced by brief ischemia/reperfusion cycles of remote organ (e.g., limb is cardioprotective. The myocardial cellular changes during RIPC responsible for this phenomenon are not currently known. The aim of this work was to identify the activation by phosphorylation of cardiac proteins following RIPC. To achieve our aim we used isobaric tandem mass tagging (TMT and reverse phase nanoliquid chromatography tandem spectrometry using a Linear Trap Quadropole (LTQ Orbitrap Velos mass spectrometer. Male C57/Bl6 mice were anesthetized by an intraperitoneal injection of Tribromoethanol. A cuff was placed around the hind limb and inflated at 200 mmHg to prevent blood flow as confirmed by Laser Doppler Flowmetry. RIPC was induced by 4 cycles of 5 min of limb ischemia followed by 5 min of reperfusion. Hearts were extracted for phosphoproteomics. We identified approximately 30 phosphoproteins that were differentially expressed in response to RIPC protocol. The levels of several phosphoproteins in the Z-disk of the sarcomere including phospho-myozenin-2 were significantly higher than control. This study describes and validates a novel approach to monitor the changes in the cardiac phosphoproteome following the cardioprotective intervention of RIPC and prior to index ischemia. The increased level of phosphorylated sarcomeric proteins suggests they may have a role in cardiac signaling during RIPC.

  18. Searching for novel Cdk5 substrates in brain by comparative phosphoproteomics of wild type and Cdk5-/- mice.

    Directory of Open Access Journals (Sweden)

    Erick Contreras-Vallejos

    Full Text Available Protein phosphorylation is the most common post-translational modification that regulates several pivotal functions in cells. Cyclin-dependent kinase 5 (Cdk5 is a proline-directed serine/threonine kinase which is mostly active in the nervous system. It regulates several biological processes such as neuronal migration, cytoskeletal dynamics, axonal guidance and synaptic plasticity among others. In search for novel substrates of Cdk5 in the brain we performed quantitative phosphoproteomics analysis, isolating phosphoproteins from whole brain derived from E18.5 Cdk5+/+ and Cdk5-/- embryos, using an Immobilized Metal-Ion Affinity Chromatography (IMAC, which specifically binds to phosphorylated proteins. The isolated phosphoproteins were eluted and isotopically labeled for relative and absolute quantitation (iTRAQ and mass spectrometry identification. We found 40 proteins that showed decreased phosphorylation at Cdk5-/- brains. In addition, out of these 40 hypophosphorylated proteins we characterized two proteins, :MARCKS (Myristoylated Alanine-Rich protein Kinase C substrate and Grin1 (G protein regulated inducer of neurite outgrowth 1. MARCKS is known to be phosphorylated by Cdk5 in chick neural cells while Grin1 has not been reported to be phosphorylated by Cdk5. When these proteins were overexpressed in N2A neuroblastoma cell line along with p35, serine phosphorylation in their Cdk5 motifs was found to be increased. In contrast, treatments with roscovitine, the Cdk5 inhibitor, resulted in an opposite effect on serine phosphorylation in N2A cells and primary hippocampal neurons transfected with MARCKS. In summary, the results presented here identify Grin 1 as novel Cdk5 substrate and confirm previously identified MARCKS as a a bona fide Cdk5 substrate.

  19. Quantitative Phosphoproteomics Unravels Biased Phosphorylation of Serotonin 2A Receptor at Ser280 by Hallucinogenic versus Nonhallucinogenic Agonists*

    Science.gov (United States)

    Karaki, Samah; Becamel, Carine; Murat, Samy; Mannoury la Cour, Clotilde; Millan, Mark J.; Prézeau, Laurent; Bockaert, Joël; Marin, Philippe; Vandermoere, Franck

    2014-01-01

    The serotonin 5-HT2A receptor is a primary target of psychedelic hallucinogens such as lysergic acid diethylamine, mescaline, and psilocybin, which reproduce some of the core symptoms of schizophrenia. An incompletely resolved paradox is that only some 5-HT2A receptor agonists exhibit hallucinogenic activity, whereas structurally related agonists with comparable affinity and activity lack such a psychoactive activity. Using a strategy combining stable isotope labeling by amino acids in cell culture with enrichment in phosphorylated peptides by means of hydrophilic interaction liquid chromatography followed by immobilized metal affinity chromatography, we compared the phosphoproteome in HEK-293 cells transiently expressing the 5-HT2A receptor and exposed to either vehicle or the synthetic hallucinogen 1-[2,5-dimethoxy-4-iodophenyl]-2-aminopropane (DOI) or the nonhallucinogenic 5-HT2A agonist lisuride. Among the 5995 identified phosphorylated peptides, 16 sites were differentially phosphorylated upon exposure of cells to DOI versus lisuride. These include a serine (Ser280) located in the third intracellular loop of the 5-HT2A receptor, a region important for its desensitization. The specific phosphorylation of Ser280 by hallucinogens was further validated by quantitative mass spectrometry analysis of immunopurified receptor digests and by Western blotting using a phosphosite specific antibody. The administration of DOI, but not of lisuride, to mice, enhanced the phosphorylation of 5-HT2A receptors at Ser280 in the prefrontal cortex. Moreover, hallucinogens induced a less pronounced desensitization of receptor-operated signaling in HEK-293 cells and neurons than did nonhallucinogenic agonists. The mutation of Ser280 to aspartic acid (to mimic phosphorylation) reduced receptor desensitization by nonhallucinogenic agonists, whereas its mutation to alanine increased the ability of hallucinogens to desensitize the receptor. This study reveals a biased phosphorylation of

  20. Combined Quantification of the Global Proteome, Phosphoproteome, and Proteolytic Cleavage to Characterize Altered Platelet Functions in the Human Scott Syndrome.

    Science.gov (United States)

    Solari, Fiorella A; Mattheij, Nadine J A; Burkhart, Julia M; Swieringa, Frauke; Collins, Peter W; Cosemans, Judith M E M; Sickmann, Albert; Heemskerk, Johan W M; Zahedi, René P

    2016-10-01

    The Scott syndrome is a very rare and likely underdiagnosed bleeding disorder associated with mutations in the gene encoding anoctamin-6. Platelets from Scott patients are impaired in various Ca 2+ -dependent responses, including phosphatidylserine exposure, integrin closure, intracellular protein cleavage, and cytoskeleton-dependent morphological changes. Given the central role of anoctamin-6 in the platelet procoagulant response, we used quantitative proteomics to understand the underlying molecular mechanisms and the complex phenotypic changes in Scott platelets compared with control platelets. Therefore, we applied an iTRAQ-based multi-pronged strategy to quantify changes in (1) the global proteome, (2) the phosphoproteome, and (3) proteolytic events between resting and stimulated Scott and control platelets. Our data indicate a limited number of proteins with decreased (70) or increased (64) expression in Scott platelets, among those we confirmed the absence of anoctamin-6 and the strong up-regulation of aquaporin-1 by parallel reaction monitoring. The quantification of 1566 phosphopeptides revealed major differences between Scott and control platelets after stimulation with thrombin/convulxin or ionomycin. In Scott platelets, phosphorylation levels of proteins regulating cytoskeletal or signaling events were increased. Finally, we quantified 1596 N-terminal peptides in activated Scott and control platelets, 180 of which we identified as calpain-regulated, whereas a distinct set of 23 neo-N termini was caspase-regulated. In Scott platelets, calpain-induced cleavage of cytoskeleton-linked and signaling proteins was downregulated, in accordance with an increased phosphorylation state. Thus, multipronged proteomic profiling of Scott platelets provides detailed insight into their protection against detrimental Ca 2+ -dependent changes that are normally associated with phosphatidylserine exposure. © 2016 by The American Society for Biochemistry and Molecular

  1. Quantitative phosphoproteomics applied to the yeast pheromone signaling pathway

    DEFF Research Database (Denmark)

    Gruhler, Albrecht; Olsen, Jesper Velgaard; Mohammed, Shabaz

    2005-01-01

    . Phosphopeptide fractions were analyzed by LC-MS using a linear ion trap-Fourier transform ion cyclotron resonance mass spectrometer. MS/MS and neutral loss-directed MS/MS/MS analysis allowed detection and sequencing of phosphopeptides with exceptional accuracy and specificity. Of more than 700 identified...

  2. Expansion of the toolbox to decipher the (phospho)proteome

    NARCIS (Netherlands)

    Hennrich, M.L.

    2012-01-01

    Nowadays, the method of choice to analyze proteins and peptides is mass spectrometry (MS). Still, several issues in the analysis of especially large pools of proteins like total cell lysates need to be solved to enable complete coverage of all proteins present in such a sample. In this thesis

  3. Developmentally-Dynamic Murine Brain Proteomes and Phosphoproteomes Revealed by Quantitative Proteomics

    Directory of Open Access Journals (Sweden)

    Peter F. Doubleday

    2014-04-01

    Full Text Available Developmental processes are governed by a diverse suite of signaling pathways employing reversible phosphorylation. Recent advances in large-scale phosphoproteomic methodologies have made possible the identification and quantification of hundreds to thousands of phosphorylation sites from primary tissues. Towards a global characterization of proteomic changes across brain development, we present the results of a large-scale quantitative mass spectrometry study comparing embryonic, newborn and adult murine brain. Using anti-phosphotyrosine immuno-affinity chromatography and strong cation exchange (SCX chromatography, coupled to immobilized metal affinity chromatography (IMAC, we identified and quantified over 1,750 phosphorylation sites and over 1,300 proteins between three developmental states. Bioinformatic analyses highlight functions associated with the identified proteins and phosphoproteins and their enrichment at distinct developmental stages. These results serve as a primary reference resource and reveal dynamic developmental profiles of proteins and phosphoproteins from the developing murine brain.

  4. ROS-activated ATM-dependent phosphorylation of cytoplasmic substrates identified by large scale phosphoproteomics screen

    DEFF Research Database (Denmark)

    Kozlov, Sergei V; Waardenberg, Ashley J; Engholm-Keller, Kasper

    2016-01-01

    checkpoints, initiating DNA repair and regulating gene expression. ATM kinase can be activated by a variety of stimuli, including oxidative stress. Here we confirmed activation of cytoplasmic ATM by autophosphorylation at multiple sites. Then we employed a global quantitative phosphoproteomics approach...... to identify cytoplasmic proteins altered in their phosphorylation state in control and A-T (ataxia-telangiectasia) cells in response to oxidative damage. We demonstrated that ATM was activated by oxidative damage in the cytoplasm as well as in the nucleus and identified a total of 9,833 phosphorylation sites......-dependent after H2O2 exposure and another protein (S100A11) demonstrated ATM-dependence for translocation from the cytoplasm to the nucleus. These data provide new insights into the activation of ATM by oxidative stress through identification of novel substrates for ATM in the cytoplasm. 2....

  5. The phosphoproteome of human Jurkat T cell clones upon costimulation with anti-CD3/anti-CD28 antibodies.

    Science.gov (United States)

    Nguyen, Tien Dung; Carrascal, Montserrat; Vidal-Cortes, Oriol; Gallardo, Oscar; Casas, Vanessa; Gay, Marina; Phan, Van Chi; Abian, Joaquin

    2016-01-10

    Phosphorylation is a reversible post-translational modification, playing a vital role in protein function. In T cells, protein phosphorylation is the key mechanism regulating T cell receptor-driven signaling pathways. In order to gain insights into the phosphoproteome evolution of T cell activation, we performed a large-scale quantitative phosphoproteomics study of Jurkat E6.1 (wild type) and Jurkat gamma1 (Phospholipase gamma1 null) cell clones upon costimulation with anti-CD3 and anti-CD28 antibodies at times ranging from 15min to as long as 120min. In total, we identified 5585 phosphopeptides belonging to 2008 phosphoproteins from both cell clones. We detected 130 and 114 novel phosphopeptides in Jurkat E6.1 and Jurkat gamma1 clones, respectively. A significantly lower number of proteins containing regulated phosphorylation sites were identified in Jurkat gamma1 in comparison to Jurkat E6.1, reflecting the vital role of Phospholipase gamma1 in T cell signaling. Several new phosphorylation sites from lymphocyte-specific protein tyrosine kinase (Lck) were identified. Of these, serine-121 showed significant changes in JE6.1 while only small changes in the Jgamma1 clone. Our data may contribute to the current human T cell phosphoproteome and provide a better understanding on T cell receptor signaling. Data are available via ProteomeXchange with identifier PXD002871. Copyright © 2015 Elsevier B.V. All rights reserved.

  6. Trajectory Based Traffic Analysis

    DEFF Research Database (Denmark)

    Krogh, Benjamin Bjerre; Andersen, Ove; Lewis-Kelham, Edwin

    2013-01-01

    -and-click analysis, due to a novel and efficient indexing structure. With the web-site daisy.aau.dk/its/spqdemo/we will demonstrate several analyses, using a very large real-world data set consisting of 1.9 billion GPS records (1.5 million trajectories) recorded from more than 13000 vehicles, and touching most...

  7. Quantitative Phosphoproteomic Study Reveals that Protein Kinase A Regulates Neural Stem Cell Differentiation Through Phosphorylation of Catenin Beta-1 and Glycogen Synthase Kinase 3β.

    Science.gov (United States)

    Wang, Shuxin; Li, Zheyi; Shen, Hongyan; Zhang, Zhong; Yin, Yuxin; Wang, Qingsong; Zhao, Xuyang; Ji, Jianguo

    2016-08-01

    Protein phosphorylation is central to the understanding of multiple cellular signaling pathways responsible for regulating the self-renewal and differentiation of neural stem cells (NSCs). Here we performed a large-scale phosphoproteomic analysis of rat fetal NSCs using strong cation exchange chromatography prefractionation and citric acid-assisted two-step enrichment with TiO2 strategy followed by nanoLC-MS/MS analysis. Totally we identified 32,546 phosphosites on 5,091 phosphoproteins, among which 23,945 were class I phosphosites, and quantified 16,000 sites during NSC differentiation. More than 65% of class I phosphosites were novel when compared with PhosphoSitePlus database. Quantification results showed that the early and late stage of NSC differentiation differ greatly. We mapped 69 changed phosphosites on 20 proteins involved in Wnt signaling pathway, including S552 on catenin beta-1 (Ctnnb1) and S9 on glycogen synthase kinase 3β (Gsk3β). Western blotting and real-time PCR results proved that Wnt signaling pathway plays critical roles in NSC fate determination. Furthermore, inhibition and activation of PKA dramatically affected the phosphorylation state of Ctnnb1 and Gsk3β, which regulates the differentiation of NSCs. Our data provides a valuable resource for studying the self-renewal and differentiation of NSCs. Stem Cells 2016;34:2090-2101. © 2016 AlphaMed Press.

  8. Non-alcoholic fatty liver disease phosphoproteomics: A functional piece of the precision puzzle.

    Science.gov (United States)

    Wattacheril, Julia; Rose, Kristie L; Hill, Salisha; Lanciault, Christian; Murray, Clark R; Washington, Kay; Williams, Brandon; English, Wayne; Spann, Matthew; Clements, Ronald; Abumrad, Naji; Flynn, Charles Robb

    2017-12-01

    Molecular signaling events associated with the necroinflammatory changes in nonalcoholic steatohepatitis (NASH) are not well understood. To understand the molecular basis of NASH, we evaluated reversible phosphorylation events in hepatic tissue derived from Class III obese subjects by phosphoproteomic means with the aim of highlighting key regulatory pathways that distinguish NASH from non-alcoholic fatty liver disease (also known as simple steatosis; SS). Class III obese subjects undergoing bariatric surgery underwent liver biopsy (eight normal patients, eight with simple steatosis, and eight NASH patients). Our strategy was unbiased, comparing global differences in liver protein reversible phosphorylation events across the 24 subjects. Of the 3078 phosphorylation sites assigned (2465 phosphoserine, 445 phosphothreonine, 165 phosphotyrosine), 53 were altered by a factor of 2 among cohorts, and of those, 12 were significantly increased or decreased by ANOVA (P < 0.05). Statistical analyses of canonical signaling pathways identified carbohydrate metabolism and RNA post-transcriptional modification among the most over-represented networks. Collectively, these results raise the possibility of abnormalities in carbohydrate metabolism as an important trigger for the development of NASH, in parallel with already established abnormalities in lipid metabolism. © 2017 The Japan Society of Hepatology.

  9. Effects of poly-ether B on proteome and phosphoproteome expression in biofouling Balanus amphitrite cyprids

    KAUST Repository

    Dash, Swagatika

    2012-04-01

    Biofouling is ubiquitous in marine environments, and the barnacle Balanus amphitrite is one of the most recalcitrant and aggressive biofoulers in tropical waters. Several natural antifoulants that were claimed to be non-toxic have been isolated in recent years, although the mechanism by which they inhibit fouling is yet to be investigated. Poly-ether B has shown promise in the non-toxic inhibition of larval barnacle attachment. Hence, in this study, multiplex two-dimensional electrophoresis (2-DE) was applied in conjunction with mass spectrometry to investigate the effects of poly-ether B on barnacle larvae at the molecular level. The cyprid proteome response to poly-ether B treatment was analyzed at the total proteome and phosphoproteome levels, with 65 protein and 19 phosphoprotein spots found to be up- or down-regulated. The proteins were found to be related to energy-metabolism, oxidative stress, and molecular chaperones, thus indicating that poly-ether B may interfere with the redox-regulatory mechanisms governing the settlement of barnacle larvae. The results of this study demonstrate the usefulness of the proteomic technique in revealing the working mechanisms of antifouling compounds. © 2012 Copyright Taylor and Francis Group, LLC.

  10. Site-Specific Ser/Thr/Tyr Phosphoproteome of Sinorhizobium meliloti at Stationary Phase.

    Directory of Open Access Journals (Sweden)

    Tao Liu

    Full Text Available Sinorhizobium meliloti, a facultative microsymbiont of alfalfa, should fine-tune its cellular processes to live saprophytically in soils characterized with limited nutrients and diverse stresses. In this study, TiO2 enrichment and LC-MS/MS were used to uncover the site-specific Ser/Thr/Tyr phosphoproteome of S. meliloti in minimum medium at stationary phase. There are a total of 96 unique phosphorylated sites, with a Ser/Thr/Tyr distribution of 63:28:5, in 77 proteins. Phosphoproteins identified in S. meliloti showed a wide distribution pattern regarding to functional categories, such as replication, transcription, translation, posttranslational modification, transport and metabolism of amino acids, carbohydrate, inorganic ion, succinoglycan etc. Ser/Thr/Tyr phosphosites identified within the conserved motif in proteins of key cellular function indicate a crucial role of phosphorylation in modulating cellular physiology. Moreover, phosphorylation in proteins involved in processes related to rhizobial adaptation was also discussed, such as those identified in SMa0114 and PhaP2 (polyhydroxybutyrate synthesis, ActR (pH stress and microaerobic adaption, SupA (potassium stress, chaperonin GroEL2 (viability and potentially symbiosis, and ExoP (succinoglycan synthesis and secretion. These Ser/Thr/Tyr phosphosites identified herein would be helpful for our further investigation and understanding of the role of phosphorylation in rhizobial physiology.

  11. FKBP12 contributes to α-synuclein toxicity by regulating the calcineurin-dependent phosphoproteome.

    Science.gov (United States)

    Caraveo, Gabriela; Soste, Martin; Cappelleti, Valentina; Fanning, Saranna; van Rossum, Damian B; Whitesell, Luke; Huang, Yanmei; Chung, Chee Yeun; Baru, Valeriya; Zaichick, Sofia; Picotti, Paola; Lindquist, Susan

    2017-12-26

    Calcineurin is an essential Ca 2+ -dependent phosphatase. Increased calcineurin activity is associated with α-synuclein (α-syn) toxicity, a protein implicated in Parkinson's Disease (PD) and other neurodegenerative diseases. Calcineurin can be inhibited with Tacrolimus through the recruitment and inhibition of the 12-kDa cis-trans proline isomerase FK506-binding protein (FKBP12). Whether calcineurin/FKBP12 represents a native physiologically relevant assembly that occurs in the absence of pharmacological perturbation has remained elusive. We leveraged α-syn as a model to interrogate whether FKBP12 plays a role in regulating calcineurin activity in the absence of Tacrolimus. We show that FKBP12 profoundly affects the calcineurin-dependent phosphoproteome, promoting the dephosphorylation of a subset of proteins that contributes to α-syn toxicity. Using a rat model of PD, partial elimination of the functional interaction between FKBP12 and calcineurin, with low doses of the Food and Drug Administration (FDA)-approved compound Tacrolimus, blocks calcineurin's activity toward those proteins and protects against the toxic hallmarks of α-syn pathology. Thus, FKBP12 can endogenously regulate calcineurin activity with therapeutic implications for the treatment of PD. Copyright © 2017 the Author(s). Published by PNAS.

  12. Phosphoproteomics reveals that Parkinson's disease kinase LRRK2 regulates a subset of Rab GTPases

    Science.gov (United States)

    Steger, Martin; Tonelli, Francesca; Ito, Genta; Davies, Paul; Trost, Matthias; Vetter, Melanie; Wachter, Stefanie; Lorentzen, Esben; Duddy, Graham; Wilson, Stephen; Baptista, Marco AS; Fiske, Brian K; Fell, Matthew J; Morrow, John A; Reith, Alastair D; Alessi, Dario R; Mann, Matthias

    2016-01-01

    Mutations in Park8, encoding for the multidomain Leucine-rich repeat kinase 2 (LRRK2) protein, comprise the predominant genetic cause of Parkinson's disease (PD). G2019S, the most common amino acid substitution activates the kinase two- to threefold. This has motivated the development of LRRK2 kinase inhibitors; however, poor consensus on physiological LRRK2 substrates has hampered clinical development of such therapeutics. We employ a combination of phosphoproteomics, genetics, and pharmacology to unambiguously identify a subset of Rab GTPases as key LRRK2 substrates. LRRK2 directly phosphorylates these both in vivo and in vitro on an evolutionary conserved residue in the switch II domain. Pathogenic LRRK2 variants mapping to different functional domains increase phosphorylation of Rabs and this strongly decreases their affinity to regulatory proteins including Rab GDP dissociation inhibitors (GDIs). Our findings uncover a key class of bona-fide LRRK2 substrates and a novel regulatory mechanism of Rabs that connects them to PD. DOI: http://dx.doi.org/10.7554/eLife.12813.001 PMID:26824392

  13. Phosphoproteomics identifies driver tyrosine kinases in sarcoma cell lines and tumors.

    Science.gov (United States)

    Bai, Yun; Li, Jiannong; Fang, Bin; Edwards, Arthur; Zhang, Guolin; Bui, Marilyn; Eschrich, Steven; Altiok, Soner; Koomen, John; Haura, Eric B

    2012-05-15

    Driver tyrosine kinase mutations are rare in sarcomas, and patterns of tyrosine phosphorylation are poorly understood. To better understand the signaling pathways active in sarcoma, we examined global tyrosine phosphorylation in sarcoma cell lines and human tumor samples. Anti-phosphotyrosine antibodies were used to purify tyrosine phosphorylated peptides, which were then identified by liquid chromatography and tandem mass spectrometry. The findings were validated with RNA interference, rescue, and small-molecule tyrosine kinase inhibitors. We identified 1,936 unique tyrosine phosphorylated peptides, corresponding to 844 unique phosphotyrosine proteins. In sarcoma cells alone, peptides corresponding to 39 tyrosine kinases were found. Four of 10 cell lines showed dependence on tyrosine kinases for growth and/or survival, including platelet-derived growth factor receptor (PDGFR)α, MET, insulin receptor/insulin-like growth factor receptor signaling, and SRC family kinase signaling. Rhabdomyosarcoma samples showed overexpression of PDGFRα in 13% of examined cases, and sarcomas showed abundant tyrosine phosphorylation and expression of a number of tyrosine phosphorylated tyrosine kinases, including DDR2, EphB4, TYR2, AXL, SRC, LYN, and FAK. Together, our findings suggest that integrating global phosphoproteomics with functional analyses with kinase inhibitors can identify drivers of sarcoma growth and survival. ©2012 AACR.

  14. Base compaction specification feasibility analysis.

    Science.gov (United States)

    2012-12-01

    The objective of this research is to establish the technical engineering and cost : analysis concepts that will enable WisDOT management to objectively evaluate the : feasibility of switching construction specification philosophies for aggregate base...

  15. Phosphoproteomics Reveals Regulatory T Cell-Mediated DEF6 Dephosphorylation That Affects Cytokine Expression in Human Conventional T Cells

    KAUST Repository

    Joshi, Rubin N.

    2017-09-25

    Regulatory T cells (Tregs) control key events of immune tolerance, primarily by suppression of effector T cells. We previously revealed that Tregs rapidly suppress T cell receptor (TCR)-induced calcium store depletion in conventional CD4CD25 T cells (Tcons) independently of IP levels, consequently inhibiting NFAT signaling and effector cytokine expression. Here, we study Treg suppression mechanisms through unbiased phosphoproteomics of primary human Tcons upon TCR stimulation and Treg-mediated suppression, respectively. Tregs induced a state of overall decreased phosphorylation as opposed to TCR stimulation. We discovered novel phosphosites (T595_S597) in the DEF6 (SLAT) protein that were phosphorylated upon TCR stimulation and conversely dephosphorylated upon coculture with Tregs. Mutation of these DEF6 phosphosites abrogated interaction of DEF6 with the IP receptor and affected NFAT activation and cytokine transcription in primary Tcons. This novel mechanism and phosphoproteomics data resource may aid in modifying sensitivity of Tcons to Treg-mediated suppression in autoimmune disease or cancer.

  16. Hand-Based Biometric Analysis

    Science.gov (United States)

    Bebis, George (Inventor); Amayeh, Gholamreza (Inventor)

    2015-01-01

    Hand-based biometric analysis systems and techniques are described which provide robust hand-based identification and verification. An image of a hand is obtained, which is then segmented into a palm region and separate finger regions. Acquisition of the image is performed without requiring particular orientation or placement restrictions. Segmentation is performed without the use of reference points on the images. Each segment is analyzed by calculating a set of Zernike moment descriptors for the segment. The feature parameters thus obtained are then fused and compared to stored sets of descriptors in enrollment templates to arrive at an identity decision. By using Zernike moments, and through additional manipulation, the biometric analysis is invariant to rotation, scale, or translation or an in put image. Additionally, the analysis utilizes re-use of commonly-seen terms in Zernike calculations to achieve additional efficiencies over traditional Zernike moment calculation.

  17. Desalting of phosphopeptides by tandem polypyrrole-c18 reverse phase micropipette tip (TMTip(PPY-C18)) based on hybrid electrostatic, Π-Π stacking and hydrophobic interactions for mass spectrometric analysis.

    Science.gov (United States)

    Zheng, Shi; Wang, Xiaoli; Fu, Jieying; Hu, Xuejiao; Xiao, Xiao; Huang, Lulu; Zhou, Youe; Zhong, Hongying

    2012-04-29

    Desalting and concentration of peptides using reverse phase (RP) C18 chromatographic material based on hydrophobic interaction is a routine approach used in mass spectrometry (MS)-based proteomics. However, MS detection of small hydrophilic peptides, in particular, phosphopeptides that bear multiple negative charges, is challenging due to the insufficient binding to C18 stationary phase. We described here the development of a new desalting method that takes the unique properties of polypyrrole (PPY). The presence of positively charged nitrogen atoms under acidic conditions and polyunsaturated bonds in polypyrrole provide a prospect for enhanced adsorption of phosphopeptides or hydrophilic peptides through extra electrostatic and Π-Π stacking interactions in addition to hydrophobic interactions. In tandem with reversed phase C18 chromatographic material, the new type of desalting method termed as TMTip(PPY-C18) can significantly improve the MS detection of phosphopeptides with multiple phosphate groups and other small hydrophilic peptides. It has been applied to not only tryptic digest of model proteins but also the analysis of complex lysates of zebrafish eggs. The number of detected phosphate groups on a peptide ranged from 1 to 6. Particularly, polypyrrole based method can also be used in basic condition. Thus it provides a useful means to handle peptides that may not be detectable in acidic condition. It can be envisioned that the TMTip(PPY-C18) should be able to facilitate the exploration of large scale phosphoproteome. Copyright © 2012 Elsevier B.V. All rights reserved.

  18. A novel multidimensional protein identification technology approach combining protein size exclusion prefractionation, peptide zwitterion-ion hydrophilic interaction chromatography, and nano-ultraperformance RP chromatography/nESI-MS2 for the in-depth analysis of the serum proteome and phosphoproteome: application to clinical sera derived from humans with benign prostate hyperplasia.

    Science.gov (United States)

    Garbis, Spiros D; Roumeliotis, Theodoros I; Tyritzis, Stavros I; Zorpas, Kostas M; Pavlakis, Kitty; Constantinides, Constantinos A

    2011-02-01

    The current proof-of-principle study was aimed toward development of a novel multidimensional protein identification technology (MudPIT) approach for the in-depth proteome analysis of human serum derived from patients with benign prostate hyperplasia (BPH) using rational chromatographic design principles. This study constituted an extension of our published work relating to the identification and relative quantification of potential clinical biomarkers in BPH and prostate cancer (PCa) tissue specimens. The proposed MudPIT approach encompassed the use of three distinct yet complementary liquid chromatographic chemistries. High-pressure size-exclusion chromatography (SEC) was used for the prefractionation of serum proteins followed by their dialysis exchange and solution phase trypsin proteolysis. The tryptic peptides were then subjected to offline zwitterion-ion hydrophilic interaction chromatography (ZIC-HILIC) fractionation followed by their online analysis with reversed-phase nano-ultraperformance chromatography (RP-nUPLC) hyphenated to nanoelectrospray ionization-tandem mass spectrometry using an ion trap mass analyzer. For the spectral processing, the sequential use of the SpectrumMill, Scaffold, and InsPecT software tools was applied for the tryptic peptide product ion MS(2) spectral processing, false discovery rate (FDR) assessment, validation, and protein identification. This milestone serum analysis study allowed the confident identification of over 1955 proteins (p ≤ 0.05; FDR ≤ 5%) with a broad spectrum of biological and physicochemical properties including secreted, tissue-specific proteins spanning approximately 12 orders of magnitude as they occur in their native abundance levels in the serum matrix. Also encompassed in this proteome was the confident identification of 375 phosphoproteins (p ≤ 0.05; FDR ≤ 5%) with potential importance to cancer biology. To demonstrate the performance characteristics of this novel MudPIT approach, a comparison

  19. Changes in the Phosphoproteome and Metabolome Link Early Signaling Events to Rearrangement of Photosynthesis and Central Metabolism in Salinity and Oxidative Stress Response in Arabidopsis.

    Science.gov (United States)

    Chen, Yanmei; Hoehenwarter, Wolfgang

    2015-12-01

    Salinity and oxidative stress are major factors affecting and limiting the productivity of agricultural crops. The molecular and biochemical processes governing the plant response to abiotic stress have often been researched in a reductionist manner. Here, we report a systemic approach combining metabolic labeling and phosphoproteomics to capture early signaling events with quantitative metabolome analysis and enzyme activity assays to determine the effects of salt and oxidative stress on plant physiology. K(+) and Na(+) transporters showed coordinated changes in their phosphorylation pattern, indicating the importance of dynamic ion homeostasis for adaptation to salt stress. Unique phosphorylation sites were found for Arabidopsis (Arabidopsis thaliana) SNF1 kinase homolog10 and 11, indicating their central roles in the stress-regulated responses. Seven Sucrose Non-fermenting1-Related Protein Kinase2 kinases showed varying levels of phosphorylation at multiple serine/threonine residues in their kinase domain upon stress, showing temporally distinct modulation of the various isoforms. Salinity and oxidative stress also lead to changes in protein phosphorylation of proteins central to photosynthesis, in particular the kinase State Transition Protein7 required for state transition and light-harvesting II complex proteins. Furthermore, stress-induced changes of the phosphorylation of enzymes of central metabolism were observed. The phosphorylation patterns of these proteins were concurrent with changes in enzyme activity. This was reflected by altered levels of metabolites, such as the sugars sucrose and fructose, glycolysis intermediates, and amino acids. Together, our study provides evidence for a link between early signaling in the salt and oxidative stress response that regulates the state transition of photosynthesis and the rearrangement of primary metabolism. © 2015 American Society of Plant Biologists. All Rights Reserved.

  20. Exploring signal transduction networks using mass spectrometry-based proteomics

    NARCIS (Netherlands)

    Meijer, L.A.T.

    2012-01-01

    Mass spectrometry (MS)-based proteomics can be used to answer a diversity of biological questions. In this thesis, we describe the application of several MS-based proteomics approaches to get insight into several aspects of signal transduction. In Chapter 2, quantitative global phosphoproteomics are

  1. Chemical phosphoproteomics and development of bisubstrate based inhibitors of protein kinase C isozymes

    NARCIS (Netherlands)

    Poot, A.J.

    2010-01-01

    Protein phosphorylation is one of the most abundant post-translational modifications. Phosphorylation is important for the function of the protein, for example it regulates enzyme activity, signal transduction and cell division. Protein phosphorylation plays a central role in virtually all crucial

  2. Unraveling the dynamics of sphingolipid metabolism by mass spectrometry based (phospho)proteomics

    NARCIS (Netherlands)

    Lebesgue, N.F.M.

    2016-01-01

    Sphingolipids (SLs) are essential components of cell membranes and are broad-range bioactive signaling molecules with imbalances affecting cellular function and contributing to pathologies ranging from neurodegenerative and metabolic disorders to cancer and aging. Deciphering how SL homeostasis is

  3. Relation chain based clustering analysis

    Science.gov (United States)

    Zhang, Cheng-ning; Zhao, Ming-yang; Luo, Hai-bo

    2011-08-01

    Clustering analysis is currently one of well-developed branches in data mining technology which is supposed to find the hidden structures in the multidimensional space called feature or pattern space. A datum in the space usually possesses a vector form and the elements in the vector represent several specifically selected features. These features are often of efficiency to the problem oriented. Generally, clustering analysis goes into two divisions: one is based on the agglomerative clustering method, and the other one is based on divisive clustering method. The former refers to a bottom-up process which regards each datum as a singleton cluster while the latter refers to a top-down process which regards entire data as a cluster. As the collected literatures, it is noted that the divisive clustering is currently overwhelming both in application and research. Although some famous divisive clustering methods are designed and well developed, clustering problems are still far from being solved. The k - means algorithm is the original divisive clustering method which initially assigns some important index values, such as the clustering number and the initial clustering prototype positions, and that could not be reasonable in some certain occasions. More than the initial problem, the k - means algorithm may also falls into local optimum, clusters in a rigid way and is not available for non-Gaussian distribution. One can see that seeking for a good or natural clustering result, in fact, originates from the one's understanding of the concept of clustering. Thus, the confusion or misunderstanding of the definition of clustering always derives some unsatisfied clustering results. One should consider the definition deeply and seriously. This paper demonstrates the nature of clustering, gives the way of understanding clustering, discusses the methodology of designing a clustering algorithm, and proposes a new clustering method based on relation chains among 2D patterns. In

  4. In vivo phosphoproteome characterization reveals key starch granule-binding phosphoproteins involved in wheat water-deficit response.

    Science.gov (United States)

    Chen, Guan-Xing; Zhen, Shou-Min; Liu, Yan-Lin; Yan, Xing; Zhang, Ming; Yan, Yue-Ming

    2017-10-23

    Drought stress during grain development causes significant yield loss in cereal production. The phosphorylated modification of starch granule-binding proteins (SGBPs) is an important mechanism regulating wheat starch biosynthesis. In this study, we performed the first proteomics and phosphoproteomics analyses of SGBPs in elite Chinese bread wheat (Triticum aestivum L.) cultivar Jingdong 17 under well-watered and water-stress conditions. Water stress treatment caused significant reductions in spike grain numbers and weight, total starch and amylopectin content, and grain yield. Two-dimensional gel electrophoresis revealed that the quantity of SGBPs was reduced significantly by water-deficit treatment. Phosphoproteome characterization of SGBPs under water-deficit treatment demonstrated a reduced level of phosphorylation of main starch synthesis enzymes, particularly for granule-bound starch synthase (GBSS I), starch synthase II-a (SS II-a), and starch synthase III (SS III). Specifically, the Ser34 site of the GBSSI protein, the Tyr358 site of SS II-a, and the Ser837 site of SS III-a exhibited significant less phosphorylation under water-deficit treatment than well-watered treatment. Furthermore, the expression levels of several key genes related with starch biosynthesis detected by qRT-PCR were decreased significantly at 15 days post-anthesis under water-deficit treatment. Immunolocalization showed a clear movement of GBSS I from the periphery to the interior of starch granules during grain development, under both water-deficit and well-watered conditions. Our results demonstrated that the reduction in gene expression or transcription level, protein expression and phosphorylation levels of starch biosynthesis related enzymes under water-deficit conditions is responsible for the significant decrease in total starch content and grain yield.

  5. Phosphoproteomic profiling analysis in pediatric acute leukemias and in solid tumors of the adult

    International Nuclear Information System (INIS)

    Basso, G.; Nitti, D.

    2009-01-01

    We analyzed 120 pediatric patients affected with B-cell AL (B-Acute Lymphoblastic Leukemia) by Reverse Phase Protein Arrays (RPPA). Leukemia cells from bone marrow aspirates were stored in liquid nitrogen in the Bio Bank of the Laboratory of Pediatric Onco hematology in Padova. Clinical data, such as immuno phenotype, outcome, response to therapy and chromosomal translocations, were collected for all the patients

  6. Phosphoproteomics analysis of postmortem porcine muscle with pH decline rate and time difference

    DEFF Research Database (Denmark)

    Huang, Honggang; Larsen, Martin R; Karlsson, Anders H

    2012-01-01

    . The sarcoplasmic and myofibrillar fractions were analyzed using gel electrophoresis in combination with a phosphoprotein specific staining. Globally, the group with fast pH decline rate had the highest phosphorylation level at PM 1 h, but lowest at PM 24 h, whereas the group with slow pH decline rate showed...

  7. Phosphoproteome analysis of E-coli reveals evolutionary conservation of bacterial Ser/Thr/Tyr phosphorylation

    DEFF Research Database (Denmark)

    Macek, B.; Gnad, F.; Soufi, Boumediene

    2008-01-01

    Protein phosphorylation on serine, threonine, and tyrosine (Ser/Thr/Tyr) is generally considered the major regulatory posttranslational modification in eukaryotic cells. Increasing evidence at the genome and proteome level shows that this modification is also present and functional in prokaryotes...

  8. Phosphoproteomic analysis of cells treated with longevity-related autophagy inducers

    DEFF Research Database (Denmark)

    Bennetzen, Martin V; Mariño, Guillermo; Pultz, Dennis

    2012-01-01

    Macroautophagy is a self-cannibalistic process that enables cells to adapt to various stresses and maintain energy homeostasis. Additionally, autophagy is an important route for turnover of misfolded proteins and damaged organelles, with important implications in cancer, neurodegenerative diseases...... to resveratrol and spermidine and that key proteins modulating the acetylation, phosphorylation, methylation and ubiquitination status were affected by changes in phosphorylation during the autophagic response. Essential parts of the apoptotic signaling network were subjected to post-translational modifications...

  9. Importance-performance analysis based SWOT analysis

    OpenAIRE

    Phadermrod, Boonyarat; Crowder, Richard M.; Wills, Gary B.

    2016-01-01

    SWOT analysis, a commonly used tool for strategic planning, is traditionally a form of brainstorming. Hence, it has been criticised that it is likely to hold subjective views of the individuals who participate in a brainstorming session and that SWOT factors are not prioritized by their significance thus it may result in an improper strategic action. While most studies of SWOT analysis have only focused on solving these shortcomings separately, this study offers an approach to diminish both s...

  10. Offline High pH Reversed-Phase Peptide Fractionation for Deep Phosphoproteome Coverage

    DEFF Research Database (Denmark)

    Batth, Tanveer S; Olsen, Jesper V

    2016-01-01

    peptide mixtures based on high pH (basic) reversed-phase chromatography prior to phosphopeptide enrichment and mass spectrometric analysis. Peptides are separated on a C18 reversed-phase column under basic conditions and fractions collected in timed intervals followed by concatenation of the fractions...

  11. 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.

  12. Complex Wavelet Based Modulation Analysis

    DEFF Research Database (Denmark)

    Luneau, Jean-Marc; Lebrun, Jérôme; Jensen, Søren Holdt

    2008-01-01

    Low-frequency modulation of sound carry important information for speech and music. The modulation spectrum i commonly obtained by spectral analysis of the sole temporal envelopes of the sub-bands out of a time-frequency analysis. Processing in this domain usually creates undesirable distortions...... polynomial trends. Moreover an analytic Hilbert-like transform is possible with complex wavelets implemented as an orthogonal filter bank. By working in an alternative transform domain coined as “Modulation Subbands”, this transform shows very promising denoising capabilities and suggests new approaches for joint...

  13. Salinity-Induced Palmella Formation Mechanism in Halotolerant Algae Dunaliella salina Revealed by Quantitative Proteomics and Phosphoproteomics

    Directory of Open Access Journals (Sweden)

    Sijia Wei

    2017-05-01

    Full Text Available Palmella stage is critical for some unicellular algae to survive in extreme environments. The halotolerant algae Dunaliella salina is a good single-cell model for studying plant adaptation to high salinity. To investigate the molecular adaptation mechanism in salinity shock-induced palmella formation, we performed a comprehensive physiological, proteomics and phosphoproteomics study upon palmella formation of D. salina using dimethyl labeling and Ti4+-immobilized metal ion affinity chromatography (IMAC proteomic approaches. We found that 151 salinity-responsive proteins and 35 salinity-responsive phosphoproteins were involved in multiple signaling and metabolic pathways upon palmella formation. Taken together with photosynthetic parameters and enzyme activity analyses, the patterns of protein accumulation and phosphorylation level exhibited the mechanisms upon palmella formation, including dynamics of cytoskeleton and cell membrane curvature, accumulation and transport of exopolysaccharides, photosynthesis and energy supplying (i.e., photosystem II stability and activity, cyclic electron transport, and C4 pathway, nuclear/chloroplastic gene expression regulation and protein processing, reactive oxygen species homeostasis, and salt signaling transduction. The salinity-responsive protein–protein interaction (PPI networks implied that signaling and protein synthesis and fate are crucial for modulation of these processes. Importantly, the 3D structure of phosphoprotein clearly indicated that the phosphorylation sites of eight proteins were localized in the region of function domain.

  14. Changes in the proteome and phosphoproteome expression in the bryozoan Bugula neritina larvae in response to the antifouling agent butenolide

    KAUST Repository

    Qian, Pei Yuan

    2010-09-08

    Larval attachment and metamorphosis, commonly referred to as larval settlement, of marine sessile invertebrates can be triggered or blocked by chemical cues and affected by changes in overall protein expression pattern and phosphorylation dynamics. This study focuses on the effects of butenolide, an effective larval settlement inhibitor, on larval settlement at the proteome level in the bryozoan Bugula neritina. Liquid-phase IEF sample prefractionation combined with 2-DE and MALDI-TOF MS was used to identify the differentially expressed proteins. Substantial changes occurred both in protein abundance and in phosphorylation status during larval settlement and when settling larvae were challenged with butenolide. The proteins that responded to treatment were identified as structural proteins, molecular chaperones, mitochondrial peptidases and calcium-binding proteins. Compared with our earlier results, both genistein and butenolide inhibited larval settlement of B. neritina primarily by changes in protein abundance and the phosphorylation status of proteins but have different protein targets in the same species. Clearly, to design potent antifouling compounds and to understand the mode of action of compounds, more studies on the effects of different compounds on proteome and phosphoproteome of different larval species are required. © 2010 Wiley-VCH Verlag GmbH & Co. KGaA.

  15. Feasibility of large-scale phosphoproteomics with higher energy collisional dissociation fragmentation

    DEFF Research Database (Denmark)

    Nagaraj, Nagarjuna; D'Souza, Rochelle C J; Cox, Juergen

    2010-01-01

    Mass spectrometry (MS)-based proteomics now enables the analysis of thousands of phosphorylation sites in single projects. Among a wide range of analytical approaches, the combination of high resolution MS scans in an Orbitrap analyzer with low resolution MS/MS scans in a linear ion trap has proven...... to be particularly successful ("high-low" strategy). Here we investigate if the improved sensitivity of higher energy collisional dissociation (HCD) on an LTQ-Orbitrap Velos instrument allows a "high-high" strategy. A high resolution MS scan was followed by up to 10 HCD MS/MS scans, and we achieved cycle times...

  16. Epoch-based analysis of speech signals

    Indian Academy of Sciences (India)

    Since the acoustic characteristics of ejective sounds differ from the corresponding voiced and voiceless pulmonic sound conjugates, mainly in the source of excitation, epoch-based analysis is useful, in addition to the spectral or spectrographic analysis. The most frequently used features for analysis of ejective sounds are: ...

  17. Target Tracking Based Scene Analysis

    Science.gov (United States)

    1984-08-01

    NATO Advanced Study PG Institute, Braunlage/ Harz , FRG, June 21 July 2, 1I82 Springer, Berlin, 1983, pp. 493-501. 141 B. Bhanu."Recognition of...Braunlage/ Harz . FRG, June 21 - July 2, 1082 Springer, Berlin, 1083. pp 10.1-124. [81 R.B. Cate, T.*1B. Dennis, J.T. Mallin, K.S. Nedelman, NEIL Trenchard, and...34Image, Sequence Processing and Dynamic Scene Analysis", Proceedings of NATO,. Advanced Study Institute, Braunlage/ Harz , FRG, June 21 - July 2, 1982

  18. Desalting of phosphopeptides by tandem polypyrrole-c18 reverse phase micropipette tip (TMTip{sub PPY-C18}) based on hybrid electrostatic, {Pi}-{Pi} stacking and hydrophobic interactions for mass spectrometric analysis

    Energy Technology Data Exchange (ETDEWEB)

    Zheng Shi; Wang Xiaoli; Fu Jieying; Hu Xuejiao; Xiao Xiao; Huang Lulu; Zhou Youe [Key Laboratory of Pesticides and Chemical Biology, Ministry of Education, College of Chemistry, Central China Normal University, Wuhan, Hubei 430079 (China); Zhong Hongying, E-mail: hyzhong@mail.ccnu.edu.cn [Key Laboratory of Pesticides and Chemical Biology, Ministry of Education, College of Chemistry, Central China Normal University, Wuhan, Hubei 430079 (China)

    2012-04-29

    Highlights: Black-Right-Pointing-Pointer A new micropipette tip TMTip{sub PPY-C18} was developed for desalting of phosphopeptides. Black-Right-Pointing-Pointer TMTip{sub PPY-C18} is based on polypyrrole in tandem with C18 chromatographic material. Black-Right-Pointing-Pointer TMTip{sub PPY-C18} combines electrostatic, {Pi}-{Pi} stacking and hydrophobic interactions. Black-Right-Pointing-Pointer TMTip{sub PPY-C18} can be used in both acidic and basic experimental conditions. - Abstract: Desalting and concentration of peptides using reverse phase (RP) C18 chromatographic material based on hydrophobic interaction is a routine approach used in mass spectrometry (MS)-based proteomics. However, MS detection of small hydrophilic peptides, in particular, phosphopeptides that bear multiple negative charges, is challenging due to the insufficient binding to C18 stationary phase. We described here the development of a new desalting method that takes the unique properties of polypyrrole (PPY). The presence of positively charged nitrogen atoms under acidic conditions and polyunsaturated bonds in polypyrrole provide a prospect for enhanced adsorption of phosphopeptides or hydrophilic peptides through extra electrostatic and {Pi}-{Pi} stacking interactions in addition to hydrophobic interactions. In tandem with reversed phase C18 chromatographic material, the new type of desalting method termed as TMTip{sub PPY-C18} can significantly improve the MS detection of phosphopeptides with multiple phosphate groups and other small hydrophilic peptides. It has been applied to not only tryptic digest of model proteins but also the analysis of complex lysates of zebrafish eggs. The number of detected phosphate groups on a peptide ranged from 1 to 6. Particularly, polypyrrole based method can also be used in basic condition. Thus it provides a useful means to handle peptides that may not be detectable in acidic condition. It can be envisioned that the TMTip{sub PPY-C18} should be able to

  19. Evidence based practice readiness: A concept analysis.

    Science.gov (United States)

    Schaefer, Jessica D; Welton, John M

    2018-01-15

    To analyse and define the concept "evidence based practice readiness" in nurses. Evidence based practice readiness is a term commonly used in health literature, but without a clear understanding of what readiness means. Concept analysis is needed to define the meaning of evidence based practice readiness. A concept analysis was conducted using Walker and Avant's method to clarify the defining attributes of evidence based practice readiness as well as antecedents and consequences. A Boolean search of PubMed and Cumulative Index for Nursing and Allied Health Literature was conducted and limited to those published after the year 2000. Eleven articles met the inclusion criteria for this analysis. Evidence based practice readiness incorporates personal and organisational readiness. Antecedents include the ability to recognize the need for evidence based practice, ability to access and interpret evidence based practice, and a supportive environment. The concept analysis demonstrates the complexity of the concept and its implications for nursing practice. The four pillars of evidence based practice readiness: nursing, training, equipping and leadership support are necessary to achieve evidence based practice readiness. Nurse managers are in the position to address all elements of evidence based practice readiness. Creating an environment that fosters evidence based practice can improve patient outcomes, decreased health care cost, increase nurses' job satisfaction and decrease nursing turnover. © 2018 John Wiley & Sons Ltd.

  20. Java based LCD reconstruction and analysis tools

    International Nuclear Information System (INIS)

    Bower, Gary; Cassell, Ron; Graf, Norman; Johnson, Tony; Ronan, Mike

    2001-01-01

    We summarize the current status and future developments of the North American Group's Java-based system for studying physics and detector design issues at a linear collider. The system is built around Java Analysis Studio (JAS) an experiment-independent Java-based utility for data analysis. Although the system is an integrated package running in JAS, many parts of it are also standalone Java utilities

  1. JAVA based LCD Reconstruction and Analysis Tools

    International Nuclear Information System (INIS)

    Bower, G.

    2004-01-01

    We summarize the current status and future developments of the North American Group's Java-based system for studying physics and detector design issues at a linear collider. The system is built around Java Analysis Studio (JAS) an experiment-independent Java-based utility for data analysis. Although the system is an integrated package running in JAS, many parts of it are also standalone Java utilities

  2. Preference-Based Recommendations for OLAP Analysis

    Science.gov (United States)

    Jerbi, Houssem; Ravat, Franck; Teste, Olivier; Zurfluh, Gilles

    This paper presents a framework for integrating OLAP and recommendations. We focus on the anticipatory recommendation process that assists the user during his OLAP analysis by proposing to him the forthcoming analysis step. We present a context-aware preference model that matches decision-makers intuition, and we discuss a preference-based approach for generating personalized recommendations.

  3. Combined Phosphoproteomics and Bioinformatics Strategy in Deciphering Drug Resistant Related Pathways in Triple Negative Breast Cancer

    Directory of Open Access Journals (Sweden)

    Xinyu Deng

    2014-01-01

    Full Text Available Because of the absence of a clear therapeutic target for triple negative breast cancer (TNBC, conventional chemotherapy is the only available systemic treatment option for these patients. Despite chemotherapy treatment, TNBC patients still have worse prognosis when compared with other breast cancer patients. The study is to investigate unique phosphorylated proteins expressed in chemoresistant TNBC cell lines. In the current study, twelve TNBC cell lines were subjected to drug sensitivity assays against chemotherapy drugs docetaxel, doxorubicin, gemcitabine, and cisplatin. Based on their half maximal inhibitory concentrations, four resistant and two sensitive cell lines were selected for further analysis. The phosphopeptides from these cells were enriched with TiO2 beads and fractionated using strong cation exchange. 1,645 phosphoprotein groups and 9,585 unique phosphopeptides were identified by a high throughput LC-MS/MS system LTQ-Orbitrap. The phosphopeptides were further filtered with Ascore system and 1,340 phosphoprotein groups, 2,760 unique phosphopeptides, and 4,549 unique phosphosites were identified. Our study suggested that differentially phosphorylated Cdk5, PML, AP-1, and HSF-1 might work together to promote vimentin induced epithelial to mesenchymal transition (EMT in the drug resistant cells. EGFR and HGF were also shown to be involved in this process.

  4. Team-Based Care: A Concept Analysis.

    Science.gov (United States)

    Baik, Dawon

    2017-10-01

    The purpose of this concept analysis is to clarify and analyze the concept of team-based care in clinical practice. Team-based care has garnered attention as a way to enhance healthcare delivery and patient care related to quality and safety. However, there is no consensus on the concept of team-based care; as a result, the lack of common definition impedes further studies on team-based care. This analysis was conducted using Walker and Avant's strategy. Literature searches were conducted using PubMed, Cumulative Index to Nursing and Allied Health Literature (CINAHL), and PsycINFO, with a timeline from January 1985 to December 2015. The analysis demonstrates that the concept of team-based care has three core attributes: (a) interprofessional collaboration, (b) patient-centered approach, and (c) integrated care process. This is accomplished through understanding other team members' roles and responsibilities, a climate of mutual respect, and organizational support. Consequences of team-based care are identified with three aspects: (a) patient, (b) healthcare professional, and (c) healthcare organization. This concept analysis helps better understand the characteristics of team-based care in the clinical practice as well as promote the development of a theoretical definition of team-based care. © 2016 Wiley Periodicals, Inc.

  5. Robust Mediation Analysis Based on Median Regression

    Science.gov (United States)

    Yuan, Ying; MacKinnon, David P.

    2014-01-01

    Mediation analysis has many applications in psychology and the social sciences. The most prevalent methods typically assume that the error distribution is normal and homoscedastic. However, this assumption may rarely be met in practice, which can affect the validity of the mediation analysis. To address this problem, we propose robust mediation analysis based on median regression. Our approach is robust to various departures from the assumption of homoscedasticity and normality, including heavy-tailed, skewed, contaminated, and heteroscedastic distributions. Simulation studies show that under these circumstances, the proposed method is more efficient and powerful than standard mediation analysis. We further extend the proposed robust method to multilevel mediation analysis, and demonstrate through simulation studies that the new approach outperforms the standard multilevel mediation analysis. We illustrate the proposed method using data from a program designed to increase reemployment and enhance mental health of job seekers. PMID:24079925

  6. Chip based electroanalytical systems for cell analysis

    DEFF Research Database (Denmark)

    Spegel, C.; Heiskanen, A.; Skjolding, L.H.D.

    2008-01-01

    ' measurements of processes related to living cells, i.e., systems without lysing the cells. The focus is on chip based amperometric and impedimetric cell analysis systems where measurements utilizing solely carbon fiber microelectrodes (CFME) and other nonchip electrode formats, such as CFME for exocytosis...

  7. Node-based analysis of species distributions

    DEFF Research Database (Denmark)

    Borregaard, Michael Krabbe; Rahbek, Carsten; Fjeldså, Jon

    2014-01-01

    with case studies on two groups with well-described biogeographical histories: a local-scale community data set of hummingbirds in the North Andes, and a large-scale data set of the distribution of all species of New World flycatchers. The node-based analysis of these two groups generates a set...

  8. Network-based analysis of proteomic profiles

    KAUST Repository

    Wong, Limsoon

    2016-01-26

    Mass spectrometry (MS)-based proteomics is a widely used and powerful tool for profiling systems-wide protein expression changes. It can be applied for various purposes, e.g. biomarker discovery in diseases and study of drug responses. Although RNA-based high-throughput methods have been useful in providing glimpses into the underlying molecular processes, the evidences they provide are indirect. Furthermore, RNA and corresponding protein levels have been known to have poor correlation. On the other hand, MS-based proteomics tend to have consistency issues (poor reproducibility and inter-sample agreement) and coverage issues (inability to detect the entire proteome) that need to be urgently addressed. In this talk, I will discuss how these issues can be addressed by proteomic profile analysis techniques that use biological networks (especially protein complexes) as the biological context. In particular, I will describe several techniques that we have been developing for network-based analysis of proteomics profile. And I will present evidence that these techniques are useful in identifying proteomics-profile analysis results that are more consistent, more reproducible, and more biologically coherent, and that these techniques allow expansion of the detected proteome to uncover and/or discover novel proteins.

  9. Texture-based analysis of COPD

    DEFF Research Database (Denmark)

    Sørensen, Lauge; Nielsen, Mads; Lo, Pechin Chien Pau

    2012-01-01

    This study presents a fully automatic, data-driven approach for texture-based quantitative analysis of chronic obstructive pulmonary disease (COPD) in pulmonary computed tomography (CT) images. The approach uses supervised learning where the class labels are, in contrast to previous work, based...... on measured lung function instead of on manually annotated regions of interest (ROIs). A quantitative measure of COPD is obtained by fusing COPD probabilities computed in ROIs within the lung fields where the individual ROI probabilities are computed using a k nearest neighbor (kNN ) classifier. The distance...... and subsequently applied to classify 200 independent images from the same screening trial. The texture-based measure was significantly better at discriminating between subjects with and without COPD than were the two most common quantitative measures of COPD in the literature, which are based on density...

  10. Differences in Beef Quality between Angus (Bos taurus taurus and Nellore (Bos taurus indicus Cattle through a Proteomic and Phosphoproteomic Approach.

    Directory of Open Access Journals (Sweden)

    Rafael Torres de Souza Rodrigues

    Full Text Available Proteins are the major constituents of muscle and are key molecules regulating the metabolic changes during conversion of muscle to meat. Brazil is one of the largest exporters of beef and most Brazilian cattle are composed by zebu (Nellore genotype. Bos indicus beef is generally leaner and tougher than Bos taurus such as Angus. The aim of this study was to compare the muscle proteomic and phosphoproteomic profile of Angus and Nellore. Seven animals of each breed previously subjected the same growth management were confined for 84 days. Proteins were extracted from Longissimus lumborum samples collected immediately after slaughter and separated by two-dimensional electrophoresis. Pro-Q Diamond stain was used in phosphoproteomics. Proteins identification was performed using matrix assisted laser desorption/ionization time-of-flight mass spectrometry. Tropomyosin alpha-1 chain, troponin-T, myosin light chain-1 fragment, cytoplasmic malate dehydrogenase, alpha-enolase and 78 kDa glucose-regulated protein were more abundant in Nellore, while myosin light chain 3, prohibitin, mitochondrial stress-70 protein and heat shock 70 kDa protein 6 were more abundant in Angus (P<0.05. Nellore had higher phosphorylation of myosin regulatory light chain-2, alpha actin-1, triosephosphate isomerase and 14-3-3 protein epsilon. However, Angus had greater phosphorylation of phosphoglucomutase-1 and troponin-T (P<0.05. Therefore, proteins involved in contraction and muscle organization, myofilaments expressed in fast or slow-twitch fibers and heat shock proteins localized in mitochondria or sarcoplasmic reticulum and involved in cell flux of calcium and apoptosis might be associated with differences in beef quality between Angus and Nellore. Furthermore, prohibitin appears to be a potential biomarker of intramuscular fat in cattle. Additionally, differences in phosphorylation of myofilaments and glycolytic enzymes could be involved with differences in muscle

  11. Hierarchically templated beads with tailored pore structure for phosphopeptide capture and phosphoproteomics

    DEFF Research Database (Denmark)

    Wierzbicka, Celina; Torsetnes, Silje B.; Jensen, Ole N.

    2017-01-01

    Two templating approaches to produce imprinted phosphotyrosine capture beads with a controllable pore structure are reported and compared with respect to their ability to enrich phosphopeptides from a tryptic peptide mixture. The beads were prepared by the polymerization of urea-based host monomers...... and crosslinkers inside the pores of macroporous silica beads with both free and immobilized template. In the final step the silica was removed by fluoride etching resulting in mesoporous polymer replicas with narrow pore size distributions, pore diameters ≈ 10 nm and surface area > 260 m2 g-1. The beads displayed...

  12. Watershed-based Morphometric Analysis: A Review

    Science.gov (United States)

    Sukristiyanti, S.; Maria, R.; Lestiana, H.

    2018-02-01

    Drainage basin/watershed analysis based on morphometric parameters is very important for watershed planning. Morphometric analysis of watershed is the best method to identify the relationship of various aspects in the area. Despite many technical papers were dealt with in this area of study, there is no particular standard classification and implication of each parameter. It is very confusing to evaluate a value of every morphometric parameter. This paper deals with the meaning of values of the various morphometric parameters, with adequate contextual information. A critical review is presented on each classification, the range of values, and their implications. Besides classification and its impact, the authors also concern about the quality of input data, either in data preparation or scale/the detail level of mapping. This review paper hopefully can give a comprehensive explanation to assist the upcoming research dealing with morphometric analysis.

  13. Characterization of the phosphoproteome and sialoproteome in brain tissues by mass spectrometry

    DEFF Research Database (Denmark)

    Ibáñez-Vea, María; Kempf, Stefan J.; Larsen, Martin R.

    2017-01-01

    Mass spectrometry is an essential tool for the characterization of proteins within neuroscience. The development of faster instruments enables neuroscientists to investigate a large proportion of the proteome in the brain in only short analysis time. Yet, a detailed functional investigation...... as well as intact sialylated N-linked glycopeptides and unmodified peptides from the same biological sample can be applied to bridge this gap in neuroscience, exemplified by a proteomic characterization of the murine brain growth spurt....... of the intrinsic biochemical processes of the brain by evaluation of the post-translational modifications in proteins is still missing. Phosphorylation and N-linked glycosylation are important protein modifications within the brain as they are involved in neural development, neurotransmission, neurite extension...

  14. Signal transduction in cerebral arteries after subarachnoid hemorrhage-a phosphoproteomic approach

    DEFF Research Database (Denmark)

    Parker, Benjamin; Larsen, Martin Røssel; Povlsen, Gro Klitgaard

    2013-01-01

    quantitative analysis of early SAH-induced phosphorylations in cerebral arteries and evaluated identified signaling components as targets for prevention of delayed vasculopathy and ischemia. Labeled phosphopeptides from rat cerebral arteries were quantified by high-resolution tandem mass spectrometry. Selected....... STAT3 inhibition partially mimicked these effects. The study shows that quantitative mass spectrometry is a strong approach to study in vivo vascular signaling. Moreover, it shows that targeting of ERK1/2 prevents delayed pathologic changes in cerebral arteries and improves outcome, and identifies SAH......-induced signaling components downstream and upstream of ERK1/2.Journal of Cerebral Blood Flow & Metabolism advance online publication, 29 May 2013; doi:10.1038/jcbfm.2013.78....

  15. A dictionary based informational genome analysis

    Directory of Open Access Journals (Sweden)

    Castellini Alberto

    2012-09-01

    Full Text Available Abstract Background In the post-genomic era several methods of computational genomics are emerging to understand how the whole information is structured within genomes. Literature of last five years accounts for several alignment-free methods, arisen as alternative metrics for dissimilarity of biological sequences. Among the others, recent approaches are based on empirical frequencies of DNA k-mers in whole genomes. Results Any set of words (factors occurring in a genome provides a genomic dictionary. About sixty genomes were analyzed by means of informational indexes based on genomic dictionaries, where a systemic view replaces a local sequence analysis. A software prototype applying a methodology here outlined carried out some computations on genomic data. We computed informational indexes, built the genomic dictionaries with different sizes, along with frequency distributions. The software performed three main tasks: computation of informational indexes, storage of these in a database, index analysis and visualization. The validation was done by investigating genomes of various organisms. A systematic analysis of genomic repeats of several lengths, which is of vivid interest in biology (for example to compute excessively represented functional sequences, such as promoters, was discussed, and suggested a method to define synthetic genetic networks. Conclusions We introduced a methodology based on dictionaries, and an efficient motif-finding software application for comparative genomics. This approach could be extended along many investigation lines, namely exported in other contexts of computational genomics, as a basis for discrimination of genomic pathologies.

  16. Energy-based dynamic reliability analysis

    International Nuclear Information System (INIS)

    Fukushima, S.; Mizutani, M.; Akao, Y.; Katukura, H.

    1993-01-01

    Dynamic reliability analysis (DRA) of structures subjected to strong ground motions is one of the most important parts of the safety assessment of structures. So far many DRA methods based on probabilistic theory have been developed. Generally, DRA methods are divided into three phases; seismic hazard analysis, fragility synthesis, and evaluation of probability of failure. In most DRA method, the seismic hazard curves of peak ground acceleration (PGA) or spectral acceleration at a certain period is evaluated to show the occurrence ratio of input motion in the seismic hazard analysis, and, in the fragility synthesis, random vibration theory is adopted to calculate the conditional probability of failure of structures given the occurrence of input motion. Since random vibration theory is developed in the frequency domain, PGAs are transformed into information in the frequency domain by means of introducing so-called peak factors and power spectra. This fact suggests that it is more convenient for DRA researchers to define the seismic hazardous the indices defined in the frequency domain from the first. In this paper, DRAs based on the two indices, i.e. PGA and total energy, are investigated in detail. Through the study, features and issues of DRA based on the total energy (hereafter called EDRA) are clarified from the viewpoint of the responses of the structure. (author)

  17. Videography-Based Unconstrained Video Analysis.

    Science.gov (United States)

    Li, Kang; Li, Sheng; Oh, Sangmin; Fu, Yun

    2017-05-01

    Video analysis and understanding play a central role in visual intelligence. In this paper, we aim to analyze unconstrained videos, by designing features and approaches to represent and analyze videography styles in the videos. Videography denotes the process of making videos. The unconstrained videos are defined as the long duration consumer videos that usually have diverse editing artifacts and significant complexity of contents. We propose to construct a videography dictionary, which can be utilized to represent every video clip as a sequence of videography words. In addition to semantic features, such as foreground object motion and camera motion, we also incorporate two novel interpretable features to characterize videography, including the scale information and the motion correlations. We then demonstrate that, by using statistical analysis methods, the unique videography signatures extracted from different events can be automatically identified. For real-world applications, we explore the use of videography analysis for three types of applications, including content-based video retrieval, video summarization (both visual and textual), and videography-based feature pooling. In the experiments, we evaluate the performance of our approach and other methods on a large-scale unconstrained video dataset, and show that the proposed approach significantly benefits video analysis in various ways.

  18. XML-based analysis interface for particle physics data analysis

    International Nuclear Information System (INIS)

    Hu Jifeng; Lu Xiaorui; Zhang Yangheng

    2011-01-01

    The letter emphasizes on an XML-based interface and its framework for particle physics data analysis. The interface uses a concise XML syntax to describe, in data analysis, the basic tasks: event-selection, kinematic fitting, particle identification, etc. and a basic processing logic: the next step goes on if and only if this step succeeds. The framework can perform an analysis without compiling by loading the XML-interface file, setting p in run-time and running dynamically. An analysis coding in XML instead of C++, easy-to-understood arid use, effectively reduces the work load, and enables users to carry out their analyses quickly. The framework has been developed on the BESⅢ offline software system (BOSS) with the object-oriented C++ programming. These functions, required by the regular tasks and the basic processing logic, are implemented with both standard modules or inherited from the modules in BOSS. The interface and its framework have been tested to perform physics analysis. (authors)

  19. Chapter 11. Community analysis-based methods

    Energy Technology Data Exchange (ETDEWEB)

    Cao, Y.; Wu, C.H.; Andersen, G.L.; Holden, P.A.

    2010-05-01

    Microbial communities are each a composite of populations whose presence and relative abundance in water or other environmental samples are a direct manifestation of environmental conditions, including the introduction of microbe-rich fecal material and factors promoting persistence of the microbes therein. As shown by culture-independent methods, different animal-host fecal microbial communities appear distinctive, suggesting that their community profiles can be used to differentiate fecal samples and to potentially reveal the presence of host fecal material in environmental waters. Cross-comparisons of microbial communities from different hosts also reveal relative abundances of genetic groups that can be used to distinguish sources. In increasing order of their information richness, several community analysis methods hold promise for MST applications: phospholipid fatty acid (PLFA) analysis, denaturing gradient gel electrophoresis (DGGE), terminal restriction fragment length polymorphism (TRFLP), cloning/sequencing, and PhyloChip. Specific case studies involving TRFLP and PhyloChip approaches demonstrate the ability of community-based analyses of contaminated waters to confirm a diagnosis of water quality based on host-specific marker(s). The success of community-based MST for comprehensively confirming fecal sources relies extensively upon using appropriate multivariate statistical approaches. While community-based MST is still under evaluation and development as a primary diagnostic tool, results presented herein demonstrate its promise. Coupled with its inherently comprehensive ability to capture an unprecedented amount of microbiological data that is relevant to water quality, the tools for microbial community analysis are increasingly accessible, and community-based approaches have unparalleled potential for translation into rapid, perhaps real-time, monitoring platforms.

  20. iTRAQ labeling is superior to mTRAQ for quantitative global proteomics and phosphoproteomics.

    Science.gov (United States)

    Mertins, Philipp; Udeshi, Namrata D; Clauser, Karl R; Mani, D R; Patel, Jinal; Ong, Shao-en; Jaffe, Jacob D; Carr, Steven A

    2012-06-01

    Labeling of primary amines on peptides with reagents containing stable isotopes is a commonly used technique in quantitative mass spectrometry. Isobaric labeling techniques such as iTRAQ™ or TMT™ allow for relative quantification of peptides based on ratios of reporter ions in the low m/z region of spectra produced by precursor ion fragmentation. In contrast, nonisobaric labeling with mTRAQ™ yields precursors with different masses that can be directly quantified in MS1 spectra. In this study, we compare iTRAQ- and mTRAQ-based quantification of peptides and phosphopeptides derived from EGF-stimulated HeLa cells. Both labels have identical chemical structures, therefore precursor ion- and fragment ion-based quantification can be directly compared. Our results indicate that iTRAQ labeling has an additive effect on precursor intensities, whereas mTRAQ labeling leads to more redundant MS2 scanning events caused by triggering on the same peptide with different mTRAQ labels. We found that iTRAQ labeling quantified nearly threefold more phosphopeptides (12,129 versus 4,448) and nearly twofold more proteins (2,699 versus 1,597) than mTRAQ labeling. Although most key proteins in the EGFR signaling network were quantified with both techniques, iTRAQ labeling allowed quantification of twice as many kinases. Accuracy of reporter ion quantification by iTRAQ is adversely affected by peptides that are cofragmented in the same precursor isolation window, dampening observed ratios toward unity. However, because of tighter overall iTRAQ ratio distributions, the percentage of statistically significantly regulated phosphopeptides and proteins detected by iTRAQ and mTRAQ was similar. We observed a linear correlation of logarithmic iTRAQ to mTRAQ ratios over two orders of magnitude, indicating a possibility to correct iTRAQ ratios by an average compression factor. Spike-in experiments using peptides of defined ratios in a background of nonregulated peptides show that i

  1. In vivo quantitative phosphoproteomic profiling identifies novel regulators of castration-resistant prostate cancer growth

    DEFF Research Database (Denmark)

    Jiang, Nan; Hjorth-Jensen, Kim; Hekmat, Omid

    2015-01-01

    timing. Interestingly, these phenotypic changes occur in the absence of obvious alterations in the activity of AKT, MAPK or mTORC1 pathways, suggesting that PAK2 and YAP1 may represent novel targets for the treatment of castration-resistant prostate cancer. Pharmacologic inhibitors of PAK2 (PF-3758309......Prostate cancer remains a leading cause of cancer-related mortality worldwide owing to our inability to treat effectively castration-resistant tumors. To understand the signaling mechanisms sustaining castration-resistant growth, we implemented a mass spectrometry-based quantitative proteomic...... approach and use it to compare protein phosphorylation in orthotopic xenograft tumors grown in either intact or castrated mice. This investigation identified changes in phosphorylation of signaling proteins such as MEK, LYN, PRAS40, YAP1 and PAK2, indicating the concomitant activation of several oncogenic...

  2. Web-based Analysis Services Report

    CERN Document Server

    AUTHOR|(CDS)2108758; Canali, Luca; Grancher, Eric; Lamanna, Massimo; McCance, Gavin; Mato Vila, Pere; Piparo, Danilo; Moscicki, Jakub; Pace, Alberto; Brito Da Rocha, Ricardo; Simko, Tibor; Smith, Tim; Tejedor Saavedra, Enric; CERN. Geneva. IT Department

    2017-01-01

    Web-based services (cloud services) is an important trend to innovate end-user services while optimising the service operational costs. CERN users are constantly proposing new approaches (inspired from services existing on the web, tools used in education or other science or based on their experience in using existing computing services). In addition, industry and open source communities have recently made available a large number of powerful and attractive tools and platforms that enable large scale data processing. “Big Data” software stacks notably provide solutions for scalable storage, distributed compute and data analysis engines, data streaming, web-based interfaces (notebooks). Some of those platforms and tools, typically available as open source products, are experiencing a very fast adoption in industry and science such that they are becoming “de facto” references in several areas of data engineering, data science and machine learning. In parallel to users' requests, WLCG is considering to c...

  3. Fault-based analysis of flexible ciphers

    Directory of Open Access Journals (Sweden)

    V.I.Korjik

    2002-07-01

    Full Text Available We consider security of some flexible ciphers against differential fault analysis (DFA. We present a description of the fault-based attack on two kinds of the flexible ciphers. The first kind is represented by the fast software-oriented cipher based on data-dependent subkey selection (DDSS, in which flexibility corresponds to the use of key-dependent operations. The second kind is represented by a DES-like cryptosystem GOST with secrete S-boxes. In general, the use of some secrete operations and procedures contributes to the security of the cryptosystem, however degree of this contribution depends significantly on the structure of the encryption mechanism. It is shown how to attack the DDSS-based flexible cipher using DFA though this cipher is secure against standard variants of the differential and linear cryptanalysis. We also give an outline of ciphers RC5 and GOST showing that they are also insecure against DFA-based attack. We suggest also a modification of the DDSS mechanism and a variant of the advanced DDSS-based flexible cipher that is secure against attacks based on random hardware faults.

  4. FINANCIAL ANALYSIS BASED ON THE ANNUAL BALANCE

    Directory of Open Access Journals (Sweden)

    ILIE RĂSCOLEAN

    2015-12-01

    Full Text Available This article demonstrates the fact that an important place in the statistical analysis of the financial management of the company goes to the analysis of the balance of assets, this representing a certain state of the capital in point of its existence, material structure and financial results obtained. It represents as well a consequence of the development of the processes forming the activity object of the company, constituting its financial framework. The balance of assets relies on the analysis liquidities-exigibility and highlights the company’s insolvency risk, namely the firm’s incapacity of honouring its commitments to third parties. The financial analysis aims to research the company’s balance statements and, especially, to measure the financial profitability starting from the balance sheet in the result account and from any other information given by the trading company or which could be obtained based on them. The authors of this article believe that by the financial analysis of the assets one can determine the net patrimony and also the accounting value of the shareholders’ shares and, respectively, one can establish the liquidity and solvency of the company, and the evaluation of the financial performances, detecting eventual situations of financial imbalance that could affect the continuity of the activity.

  5. Identifying novel targets of oncogenic EGF receptor signaling in lung cancer through global phosphoproteomics.

    Science.gov (United States)

    Zhang, Xu; Belkina, Natalya; Jacob, Harrys Kishore Charles; Maity, Tapan; Biswas, Romi; Venugopalan, Abhilash; Shaw, Patrick G; Kim, Min-Sik; Chaerkady, Raghothama; Pandey, Akhilesh; Guha, Udayan

    2015-01-01

    Mutations in the epidermal growth factor receptor (EGFR) kinase domain occur in 10-30% of lung adenocarcinoma and are associated with tyrosine kinase inhibitor (TKI) sensitivity. We sought to identify the immediate direct and indirect phosphorylation targets of mutant EGFRs in lung adenocarcinoma. We undertook SILAC strategy, phosphopeptide enrichment, and quantitative MS to identify dynamic changes of phosphorylation downstream of mutant EGFRs in lung adenocarcinoma cells harboring EGFR(L858R) and EGFR(L858R/T790M) , the TKI-sensitive, and TKI-resistant mutations, respectively. Top canonical pathways that were inhibited upon erlotinib treatment in sensitive cells, but not in the resistant cells include EGFR, insulin receptor, hepatocyte growth factor, mitogen-activated protein kinase, mechanistic target of rapamycin, ribosomal protein S6 kinase beta 1, and Janus kinase/signal transducer and activator of transcription signaling. We identified phosphosites in proteins of the autophagy network, such as ULK1 (S623) that is constitutively phosphorylated in these lung adenocarcinoma cells; phosphorylation is inhibited upon erlotinib treatment in sensitive cells, but not in resistant cells. Finally, kinase-substrate prediction analysis from our data indicated that substrates of basophilic kinases from, AGC and Calcium and calmodulin-dependent kinase groups, as well as STE group kinases were significantly enriched and those of proline-directed kinases from, CMGC and Casein kinase groups were significantly depleted among substrates that exhibited increased phosphorylation upon EGF stimulation and reduced phosphorylation upon TKI inhibition. This is the first study to date to examine global phosphorylation changes upon erlotinib treatment of lung adenocarcinoma cells and results from this study provide new insights into signaling downstream of mutant EGFRs in lung adenocarcinoma. All MS data have been deposited in the ProteomeXchange with identifier PXD001101 (http

  6. Risk analysis based on hazards interactions

    Science.gov (United States)

    Rossi, Lauro; Rudari, Roberto; Trasforini, Eva; De Angeli, Silvia; Becker, Joost

    2017-04-01

    Despite an increasing need for open, transparent, and credible multi-hazard risk assessment methods, models, and tools, the availability of comprehensive risk information needed to inform disaster risk reduction is limited, and the level of interaction across hazards is not systematically analysed. Risk assessment methodologies for different hazards often produce risk metrics that are not comparable. Hazard interactions (consecutive occurrence two or more different events) are generally neglected, resulting in strongly underestimated risk assessment in the most exposed areas. This study presents cases of interaction between different hazards, showing how subsidence can affect coastal and river flood risk (Jakarta and Bandung, Indonesia) or how flood risk is modified after a seismic event (Italy). The analysis of well documented real study cases, based on a combination between Earth Observation and in-situ data, would serve as basis the formalisation of a multi-hazard methodology, identifying gaps and research frontiers. Multi-hazard risk analysis is performed through the RASOR platform (Rapid Analysis and Spatialisation Of Risk). A scenario-driven query system allow users to simulate future scenarios based on existing and assumed conditions, to compare with historical scenarios, and to model multi-hazard risk both before and during an event (www.rasor.eu).

  7. NASA Lunar Base Wireless System Propagation Analysis

    Science.gov (United States)

    Hwu, Shian U.; Upanavage, Matthew; Sham, Catherine C.

    2007-01-01

    There have been many radio wave propagation studies using both experimental and theoretical techniques over the recent years. However, most of studies have been in support of commercial cellular phone wireless applications. The signal frequencies are mostly at the commercial cellular and Personal Communications Service bands. The antenna configurations are mostly one on a high tower and one near the ground to simulate communications between a cellular base station and a mobile unit. There are great interests in wireless communication and sensor systems for NASA lunar missions because of the emerging importance of establishing permanent lunar human exploration bases. Because of the specific lunar terrain geometries and RF frequencies of interest to the NASA missions, much of the published literature for the commercial cellular and PCS bands of 900 and 1800 MHz may not be directly applicable to the lunar base wireless system and environment. There are various communication and sensor configurations required to support all elements of a lunar base. For example, the communications between astronauts, between astronauts and the lunar vehicles, between lunar vehicles and satellites on the lunar orbits. There are also various wireless sensor systems among scientific, experimental sensors and data collection ground stations. This presentation illustrates the propagation analysis of the lunar wireless communication and sensor systems taking into account the three dimensional terrain multipath effects. It is observed that the propagation characteristics are significantly affected by the presence of the lunar terrain. The obtained results indicate the lunar surface material, terrain geometry and antenna location are the important factors affecting the propagation characteristics of the lunar wireless systems. The path loss can be much more severe than the free space propagation and is greatly affected by the antenna height, surface material and operating frequency. The

  8. Optimal depth-based regional frequency analysis

    Directory of Open Access Journals (Sweden)

    H. Wazneh

    2013-06-01

    Full Text Available Classical methods of regional frequency analysis (RFA of hydrological variables face two drawbacks: (1 the restriction to a particular region which can lead to a loss of some information and (2 the definition of a region that generates a border effect. To reduce the impact of these drawbacks on regional modeling performance, an iterative method was proposed recently, based on the statistical notion of the depth function and a weight function φ. This depth-based RFA (DBRFA approach was shown to be superior to traditional approaches in terms of flexibility, generality and performance. The main difficulty of the DBRFA approach is the optimal choice of the weight function ϕ (e.g., φ minimizing estimation errors. In order to avoid a subjective choice and naïve selection procedures of φ, the aim of the present paper is to propose an algorithm-based procedure to optimize the DBRFA and automate the choice of ϕ according to objective performance criteria. This procedure is applied to estimate flood quantiles in three different regions in North America. One of the findings from the application is that the optimal weight function depends on the considered region and can also quantify the region's homogeneity. By comparing the DBRFA to the canonical correlation analysis (CCA method, results show that the DBRFA approach leads to better performances both in terms of relative bias and mean square error.

  9. Optimal depth-based regional frequency analysis

    Science.gov (United States)

    Wazneh, H.; Chebana, F.; Ouarda, T. B. M. J.

    2013-06-01

    Classical methods of regional frequency analysis (RFA) of hydrological variables face two drawbacks: (1) the restriction to a particular region which can lead to a loss of some information and (2) the definition of a region that generates a border effect. To reduce the impact of these drawbacks on regional modeling performance, an iterative method was proposed recently, based on the statistical notion of the depth function and a weight function φ. This depth-based RFA (DBRFA) approach was shown to be superior to traditional approaches in terms of flexibility, generality and performance. The main difficulty of the DBRFA approach is the optimal choice of the weight function ϕ (e.g., φ minimizing estimation errors). In order to avoid a subjective choice and naïve selection procedures of φ, the aim of the present paper is to propose an algorithm-based procedure to optimize the DBRFA and automate the choice of ϕ according to objective performance criteria. This procedure is applied to estimate flood quantiles in three different regions in North America. One of the findings from the application is that the optimal weight function depends on the considered region and can also quantify the region's homogeneity. By comparing the DBRFA to the canonical correlation analysis (CCA) method, results show that the DBRFA approach leads to better performances both in terms of relative bias and mean square error.

  10. Gait Correlation Analysis Based Human Identification

    Directory of Open Access Journals (Sweden)

    Jinyan Chen

    2014-01-01

    Full Text Available Human gait identification aims to identify people by a sequence of walking images. Comparing with fingerprint or iris based identification, the most important advantage of gait identification is that it can be done at a distance. In this paper, silhouette correlation analysis based human identification approach is proposed. By background subtracting algorithm, the moving silhouette figure can be extracted from the walking images sequence. Every pixel in the silhouette has three dimensions: horizontal axis (x, vertical axis (y, and temporal axis (t. By moving every pixel in the silhouette image along these three dimensions, we can get a new silhouette. The correlation result between the original silhouette and the new one can be used as the raw feature of human gait. Discrete Fourier transform is used to extract features from this correlation result. Then, these features are normalized to minimize the affection of noise. Primary component analysis method is used to reduce the features’ dimensions. Experiment based on CASIA database shows that this method has an encouraging recognition performance.

  11. Dependent failure analysis of NPP data bases

    International Nuclear Information System (INIS)

    Cooper, S.E.; Lofgren, E.V.; Samanta, P.K.; Wong Seemeng

    1993-01-01

    A technical approach for analyzing plant-specific data bases for vulnerabilities to dependent failures has been developed and applied. Since the focus of this work is to aid in the formulation of defenses to dependent failures, rather than to quantify dependent failure probabilities, the approach of this analysis is critically different. For instance, the determination of component failure dependencies has been based upon identical failure mechanisms related to component piecepart failures, rather than failure modes. Also, component failures involving all types of component function loss (e.g., catastrophic, degraded, incipient) are equally important to the predictive purposes of dependent failure defense development. Consequently, dependent component failures are identified with a different dependent failure definition which uses a component failure mechanism categorization scheme in this study. In this context, clusters of component failures which satisfy the revised dependent failure definition are termed common failure mechanism (CFM) events. Motor-operated valves (MOVs) in two nuclear power plant data bases have been analyzed with this approach. The analysis results include seven different failure mechanism categories; identified potential CFM events; an assessment of the risk-significance of the potential CFM events using existing probabilistic risk assessments (PRAs); and postulated defenses to the identified potential CFM events. (orig.)

  12. Online Nanoflow Multidimensional Fractionation for High Efficiency Phosphopeptide Analysis*

    Science.gov (United States)

    Ficarro, Scott B.; Zhang, Yi; Carrasco-Alfonso, Marlene J.; Garg, Brijesh; Adelmant, Guillaume; Webber, James T.; Luckey, C. John; Marto, Jarrod A.

    2011-01-01

    Despite intense, continued interest in global analyses of signaling cascades through mass spectrometry-based studies, the large-scale, systematic production of phosphoproteomics data has been hampered in-part by inefficient fractionation strategies subsequent to phosphopeptide enrichment. Here we explore two novel multidimensional fractionation strategies for analysis of phosphopeptides. In the first technique we utilize aliphatic ion pairing agents to improve retention of phosphopeptides at high pH in the first dimension of a two-dimensional RP-RP. The second approach is based on the addition of strong anion exchange as the second dimension in a three-dimensional reversed phase (RP)-strong anion exchange (SAX)-RP configuration. Both techniques provide for automated, online data acquisition, with the 3-D platform providing the highest performance both in terms of separation peak capacity and the number of unique phosphopeptide sequences identified per μg of cell lysate consumed. Our integrated RP-SAX-RP platform provides several analytical figures of merit, including: (1) orthogonal separation mechanisms in each dimension; (2) high separation peak capacity (3) efficient retention of singly- and multiply-phosphorylated peptides; (4) compatibility with automated, online LC-MS analysis. We demonstrate the reproducibility of RP-SAX-RP and apply it to the analysis of phosphopeptides derived from multiple biological contexts, including an in vitro model of acute myeloid leukemia in addition to primary polyclonal CD8+ T-cells activated in vivo through bacterial infection and then purified from a single mouse. PMID:21788404

  13. Rweb:Web-based Statistical Analysis

    Directory of Open Access Journals (Sweden)

    Jeff Banfield

    1999-03-01

    Full Text Available Rweb is a freely accessible statistical analysis environment that is delivered through the World Wide Web (WWW. It is based on R, a well known statistical analysis package. The only requirement to run the basic Rweb interface is a WWW browser that supports forms. If you want graphical output you must, of course, have a browser that supports graphics. The interface provides access to WWW accessible data sets, so you may run Rweb on your own data. Rweb can provide a four window statistical computing environment (code input, text output, graphical output, and error information through browsers that support Javascript. There is also a set of point and click modules under development for use in introductory statistics courses.

  14. Thermal-Signature-Based Sleep Analysis Sensor

    Directory of Open Access Journals (Sweden)

    Ali Seba

    2017-10-01

    Full Text Available This paper addresses the development of a new technique in the sleep analysis domain. Sleep is defined as a periodic physiological state during which vigilance is suspended and reactivity to external stimulations diminished. We sleep on average between six and nine hours per night and our sleep is composed of four to six cycles of about 90 min each. Each of these cycles is composed of a succession of several stages of sleep that vary in depth. Analysis of sleep is usually done via polysomnography. This examination consists of recording, among other things, electrical cerebral activity by electroencephalography (EEG, ocular movements by electrooculography (EOG, and chin muscle tone by electromyography (EMG. Recordings are made mostly in a hospital, more specifically in a service for monitoring the pathologies related to sleep. The readings are then interpreted manually by an expert to generate a hypnogram, a curve showing the succession of sleep stages during the night in 30s epochs. The proposed method is based on the follow-up of the thermal signature that makes it possible to classify the activity into three classes: “awakening,” “calm sleep,” and “restless sleep”. The contribution of this non-invasive method is part of the screening of sleep disorders, to be validated by a more complete analysis of the sleep. The measure provided by this new system, based on temperature monitoring (patient and ambient, aims to be integrated into the tele-medicine platform developed within the framework of the Smart-EEG project by the SYEL–SYstèmes ELectroniques team. Analysis of the data collected during the first surveys carried out with this method showed a correlation between thermal signature and activity during sleep. The advantage of this method lies in its simplicity and the possibility of carrying out measurements of activity during sleep and without direct contact with the patient at home or hospitals.

  15. Experimental data base for containment thermalhydraulic analysis

    International Nuclear Information System (INIS)

    Cheng, X.; Bazin, P.; Cornet, P.; Hittner, D.; Jackson, J.D.; Lopez Jimenez, J.; Naviglio, A.; Oriolo, F.; Petzold, H.

    2001-01-01

    This paper describes the joint research project DABASCO which is supported by the European Community under a cost-shared contract and participated by nine European institutions. The main objective of the project is to provide a generic experimental data base for the development of physical models and correlations for containment thermalhydraulic analysis. The project consists of seven separate-effects experimental programs which deal with new innovative conceptual features, e.g. passive decay heat removal and spray systems. The results of the various stages of the test programs will be assessed by industrial partners in relation to their applicability to reactor conditions

  16. Similarity-based pattern analysis and recognition

    CERN Document Server

    Pelillo, Marcello

    2013-01-01

    This accessible text/reference presents a coherent overview of the emerging field of non-Euclidean similarity learning. The book presents a broad range of perspectives on similarity-based pattern analysis and recognition methods, from purely theoretical challenges to practical, real-world applications. The coverage includes both supervised and unsupervised learning paradigms, as well as generative and discriminative models. Topics and features: explores the origination and causes of non-Euclidean (dis)similarity measures, and how they influence the performance of traditional classification alg

  17. Global phosphoproteomic analysis of human skeletal muscle reveals a network of exercise-regulated kinases and AMPK substrates

    DEFF Research Database (Denmark)

    Hoffman, Nolan J; Parker, Benjamin L; Chaudhuri, Rima

    2015-01-01

    -intensity exercise bout, revealing 1,004 unique exercise-regulated phosphosites on 562 proteins. These included substrates of known exercise-regulated kinases (AMPK, PKA, CaMK, MAPK, mTOR), yet the majority of kinases and substrate phosphosites have not previously been implicated in exercise signaling. Given...

  18. Nuclear phosphoproteome analysis of 3T3-L1 preadipocyte differentiation reveals system-wide phosphorylation of transcriptional regulators

    DEFF Research Database (Denmark)

    Rabiee, Atefeh; Schwämmle, Veit; Sidoli, Simone

    2017-01-01

    of which were assigned as regulators of gene expression. Among 288 identified transcriptional regulators, 49 were regulated within four hours of adipogenic stimulation including several known and many novel potential adipogenic regulators. A kinase-substrate database for 3T3-L1 preadipocytes established...... stages (4 hours) of preadipocyte differentiation. We identified a total of 4072 proteins including 2434 phosphorylated proteins, a majority of which were assigned as regulators of gene expression. Our results demonstrate that adipogenic stimuli increase the nuclear abundance and/or the phosphorylation...... for 3T3-L1 preadipocytes by investigating the relationship between protein kinases and protein phosphorylation sites identified in our dataset. A majority of the putative protein kinases belong to the cyclin-dependent kinase (CDK) family and the mitogen activated protein kinase (MAPK) family including P...

  19. Identification of novel PAMP-triggered phosphorylation and dephosphorylation events in arabidopsis thaliana by quantitative phosphoproteomic analysis

    KAUST Repository

    Rayapuram, Naganand

    2014-04-04

    Signaling cascades rely strongly on protein kinase-mediated substrate phosphorylation. Currently a major challenge in signal transduction research is to obtain high confidence substrate phosphorylation sites and assign them to specific kinases. In response to bacterial flagellin, a pathogen-associated molecular pattern (PAMP), we searched for rapidly phosphorylated proteins in Arabidopsis thaliana by combining multistage activation (MSA) and electron transfer dissociation (ETD) fragmentation modes, which generate complementary spectra and identify phosphopeptide sites with increased reliability. Of a total of 825 phosphopeptides, we identified 58 to be differentially phosphorylated. These peptides harbor kinase motifs of mitogen-activated protein kinases (MAPKs) and calcium-dependent protein kinases (CDPKs), as well as yet unknown protein kinases. Importantly, 12 of the phosphopeptides show reduced phosphorylation upon flagellin treatment. Since protein abundance levels did not change, these results indicate that flagellin induces not only various protein kinases but also protein phosphatases, even though a scenario of inhibited kinase activity may also be possible. © 2014 American Chemical Society.

  20. Motion Analysis Based on Invertible Rapid Transform

    Directory of Open Access Journals (Sweden)

    J. Turan

    1999-06-01

    Full Text Available This paper presents the results of a study on the use of invertible rapid transform (IRT for the motion estimation in a sequence of images. Motion estimation algorithms based on the analysis of the matrix of states (produced in the IRT calculation are described. The new method was used experimentally to estimate crowd and traffic motion from the image data sequences captured at railway stations and at high ways in large cities. The motion vectors may be used to devise a polar plot (showing velocity magnitude and direction for moving objects where the dominant motion tendency can be seen. The experimental results of comparison of the new motion estimation methods with other well known block matching methods (full search, 2D-log, method based on conventional (cross correlation (CC function or phase correlation (PC function for application of crowd motion estimation are also presented.

  1. Visibility Graph Based Time Series Analysis.

    Science.gov (United States)

    Stephen, Mutua; Gu, Changgui; Yang, Huijie

    2015-01-01

    Network based time series analysis has made considerable achievements in the recent years. By mapping mono/multivariate time series into networks, one can investigate both it's microscopic and macroscopic behaviors. However, most proposed approaches lead to the construction of static networks consequently providing limited information on evolutionary behaviors. In the present paper we propose a method called visibility graph based time series analysis, in which series segments are mapped to visibility graphs as being descriptions of the corresponding states and the successively occurring states are linked. This procedure converts a time series to a temporal network and at the same time a network of networks. Findings from empirical records for stock markets in USA (S&P500 and Nasdaq) and artificial series generated by means of fractional Gaussian motions show that the method can provide us rich information benefiting short-term and long-term predictions. Theoretically, we propose a method to investigate time series from the viewpoint of network of networks.

  2. DTI Analysis of Presbycusis Using Voxel-Based Analysis.

    Science.gov (United States)

    Ma, W; Li, M; Gao, F; Zhang, X; Shi, L; Yu, L; Zhao, B; Chen, W; Wang, G; Wang, X

    2016-07-14

    Presbycusis is the most common sensory deficit in the aging population. A recent study reported using a DTI-based tractography technique to identify a lack of integrity in a portion of the auditory pathway in patients with presbycusis. The aim of our study was to investigate the white matter pathology of patients with presbycusis by using a voxel-based analysis that is highly sensitive to local intensity changes in DTI data. Fifteen patients with presbycusis and 14 age- and sex-matched healthy controls were scanned on a 3T scanner. Fractional anisotropy, mean diffusivity, axial diffusivity, and radial diffusivity were obtained from the DTI data. Intergroup statistics were implemented on these measurements, which were transformed to Montreal Neurological Institute coordinates by using a nonrigid image registration method called large deformation diffeomorphic metric mapping. Increased axial diffusivity, radial diffusivity, and mean diffusivity and decreased fractional anisotropy were found near the right-side hearing-related areas in patients with presbycusis. Increased radial diffusivity and mean diffusivity were also found near a language-related area (Broca area) in patients with presbycusis. Our findings could be important for exploring reliable imaging evidence of presbycusis and could complement an ROI-based approach. © 2016 American Society of Neuroradiology.

  3. Curvelet based offline analysis of SEM images.

    Directory of Open Access Journals (Sweden)

    Syed Hamad Shirazi

    Full Text Available Manual offline analysis, of a scanning electron microscopy (SEM image, is a time consuming process and requires continuous human intervention and efforts. This paper presents an image processing based method for automated offline analyses of SEM images. To this end, our strategy relies on a two-stage process, viz. texture analysis and quantification. The method involves a preprocessing step, aimed at the noise removal, in order to avoid false edges. For texture analysis, the proposed method employs a state of the art Curvelet transform followed by segmentation through a combination of entropy filtering, thresholding and mathematical morphology (MM. The quantification is carried out by the application of a box-counting algorithm, for fractal dimension (FD calculations, with the ultimate goal of measuring the parameters, like surface area and perimeter. The perimeter is estimated indirectly by counting the boundary boxes of the filled shapes. The proposed method, when applied to a representative set of SEM images, not only showed better results in image segmentation but also exhibited a good accuracy in the calculation of surface area and perimeter. The proposed method outperforms the well-known Watershed segmentation algorithm.

  4. Cluster-based exposure variation analysis

    Science.gov (United States)

    2013-01-01

    Background Static posture, repetitive movements and lack of physical variation are known risk factors for work-related musculoskeletal disorders, and thus needs to be properly assessed in occupational studies. The aims of this study were (i) to investigate the effectiveness of a conventional exposure variation analysis (EVA) in discriminating exposure time lines and (ii) to compare it with a new cluster-based method for analysis of exposure variation. Methods For this purpose, we simulated a repeated cyclic exposure varying within each cycle between “low” and “high” exposure levels in a “near” or “far” range, and with “low” or “high” velocities (exposure change rates). The duration of each cycle was also manipulated by selecting a “small” or “large” standard deviation of the cycle time. Theses parameters reflected three dimensions of exposure variation, i.e. range, frequency and temporal similarity. Each simulation trace included two realizations of 100 concatenated cycles with either low (ρ = 0.1), medium (ρ = 0.5) or high (ρ = 0.9) correlation between the realizations. These traces were analyzed by conventional EVA, and a novel cluster-based EVA (C-EVA). Principal component analysis (PCA) was applied on the marginal distributions of 1) the EVA of each of the realizations (univariate approach), 2) a combination of the EVA of both realizations (multivariate approach) and 3) C-EVA. The least number of principal components describing more than 90% of variability in each case was selected and the projection of marginal distributions along the selected principal component was calculated. A linear classifier was then applied to these projections to discriminate between the simulated exposure patterns, and the accuracy of classified realizations was determined. Results C-EVA classified exposures more correctly than univariate and multivariate EVA approaches; classification accuracy was 49%, 47% and 52% for EVA (univariate

  5. Voxel-Based LIDAR Analysis and Applications

    Science.gov (United States)

    Hagstrom, Shea T.

    One of the greatest recent changes in the field of remote sensing is the addition of high-quality Light Detection and Ranging (LIDAR) instruments. In particular, the past few decades have been greatly beneficial to these systems because of increases in data collection speed and accuracy, as well as a reduction in the costs of components. These improvements allow modern airborne instruments to resolve sub-meter details, making them ideal for a wide variety of applications. Because LIDAR uses active illumination to capture 3D information, its output is fundamentally different from other modalities. Despite this difference, LIDAR datasets are often processed using methods appropriate for 2D images and that do not take advantage of its primary virtue of 3-dimensional data. It is this problem we explore by using volumetric voxel modeling. Voxel-based analysis has been used in many applications, especially medical imaging, but rarely in traditional remote sensing. In part this is because the memory requirements are substantial when handling large areas, but with modern computing and storage this is no longer a significant impediment. Our reason for using voxels to model scenes from LIDAR data is that there are several advantages over standard triangle-based models, including better handling of overlapping surfaces and complex shapes. We show how incorporating system position information from early in the LIDAR point cloud generation process allows radiometrically-correct transmission and other novel voxel properties to be recovered. This voxelization technique is validated on simulated data using the Digital Imaging and Remote Sensing Image Generation (DIRSIG) software, a first-principles based ray-tracer developed at the Rochester Institute of Technology. Voxel-based modeling of LIDAR can be useful on its own, but we believe its primary advantage is when applied to problems where simpler surface-based 3D models conflict with the requirement of realistic geometry. To

  6. Joint multifractal analysis based on wavelet leaders

    Science.gov (United States)

    Jiang, Zhi-Qiang; Yang, Yan-Hong; Wang, Gang-Jin; Zhou, Wei-Xing

    2017-12-01

    Mutually interacting components form complex systems and these components usually have long-range cross-correlated outputs. Using wavelet leaders, we propose a method for characterizing the joint multifractal nature of these long-range cross correlations; we call this method joint multifractal analysis based on wavelet leaders (MF-X-WL). We test the validity of the MF-X-WL method by performing extensive numerical experiments on dual binomial measures with multifractal cross correlations and bivariate fractional Brownian motions (bFBMs) with monofractal cross correlations. Both experiments indicate that MF-X-WL is capable of detecting cross correlations in synthetic data with acceptable estimating errors. We also apply the MF-X-WL method to pairs of series from financial markets (returns and volatilities) and online worlds (online numbers of different genders and different societies) and determine intriguing joint multifractal behavior.

  7. Bismuth-based electrochemical stripping analysis

    Science.gov (United States)

    Wang, Joseph

    2004-01-27

    Method and apparatus for trace metal detection and analysis using bismuth-coated electrodes and electrochemical stripping analysis. Both anodic stripping voltammetry and adsorptive stripping analysis may be employed.

  8. Operating cost analysis of anaesthesia: Activity based costing (ABC analysis

    Directory of Open Access Journals (Sweden)

    Majstorović Branislava M.

    2011-01-01

    Full Text Available Introduction. Cost of anaesthesiology represent defined measures to determine a precise profile of expenditure estimation of surgical treatment, which is important regarding planning of healthcare activities, prices and budget. Objective. In order to determine the actual value of anaestesiological services, we started with the analysis of activity based costing (ABC analysis. Methods. Retrospectively, in 2005 and 2006, we estimated the direct costs of anestesiological services (salaries, drugs, supplying materials and other: analyses and equipment. of the Institute of Anaesthesia and Resuscitation of the Clinical Centre of Serbia. The group included all anesthetized patients of both sexes and all ages. We compared direct costs with direct expenditure, “each cost object (service or unit” of the Republican Health-care Insurance. The Summary data of the Departments of Anaesthesia documented in the database of the Clinical Centre of Serbia. Numerical data were utilized and the numerical data were estimated and analyzed by computer programs Microsoft Office Excel 2003 and SPSS for Windows. We compared using the linear model of direct costs and unit costs of anaesthesiological services from the Costs List of the Republican Health-care Insurance. Results. Direct costs showed 40% of costs were spent on salaries, (32% on drugs and supplies, and 28% on other costs, such as analyses and equipment. The correlation of the direct costs of anaestesiological services showed a linear correlation with the unit costs of the Republican Healthcare Insurance. Conclusion. During surgery, costs of anaesthesia would increase by 10% the surgical treatment cost of patients. Regarding the actual costs of drugs and supplies, we do not see any possibility of costs reduction. Fixed elements of direct costs provide the possibility of rationalization of resources in anaesthesia.

  9. [Operating cost analysis of anaesthesia: activity based costing (ABC analysis)].

    Science.gov (United States)

    Majstorović, Branislava M; Kastratović, Dragana A; Vučović, Dragan S; Milaković, Branko D; Miličić, Biljana R

    2011-01-01

    Cost of anaesthesiology represent defined measures to determine a precise profile of expenditure estimation of surgical treatment, which is important regarding planning of healthcare activities, prices and budget. In order to determine the actual value of anaestesiological services, we started with the analysis of activity based costing (ABC) analysis. Retrospectively, in 2005 and 2006, we estimated the direct costs of anestesiological services (salaries, drugs, supplying materials and other: analyses and equipment.) of the Institute of Anaesthesia and Resuscitation of the Clinical Centre of Serbia. The group included all anesthetized patients of both sexes and all ages. We compared direct costs with direct expenditure, "each cost object (service or unit)" of the Republican Healthcare Insurance. The Summary data of the Departments of Anaesthesia documented in the database of the Clinical Centre of Serbia. Numerical data were utilized and the numerical data were estimated and analyzed by computer programs Microsoft Office Excel 2003 and SPSS for Windows. We compared using the linear model of direct costs and unit costs of anaesthesiological services from the Costs List of the Republican Healthcare Insurance. Direct costs showed 40% of costs were spent on salaries, (32% on drugs and supplies, and 28% on other costs, such as analyses and equipment. The correlation of the direct costs of anaestesiological services showed a linear correlation with the unit costs of the Republican Healthcare Insurance. During surgery, costs of anaesthesia would increase by 10% the surgical treatment cost of patients. Regarding the actual costs of drugs and supplies, we do not see any possibility of costs reduction. Fixed elements of direct costs provide the possibility of rationalization of resources in anaesthesia.

  10. OHBM 2017: Practical intensity based meta-analysis

    OpenAIRE

    Maumet, Camille

    2017-01-01

    "Practical intensity-based meta-analysis" slides from my talk in the OHBM 2017 educational talk on Neuroimaging meta-analysis.http://www.humanbrainmapping.org/files/2017/ED Courses/Neuroimaging Meta-Analysis.pdf

  11. Communication Base Station Log Analysis Based on Hierarchical Clustering

    Directory of Open Access Journals (Sweden)

    Zhang Shao-Hua

    2017-01-01

    Full Text Available Communication base stations generate massive data every day, these base station logs play an important value in mining of the business circles. This paper use data mining technology and hierarchical clustering algorithm to group the scope of business circle for the base station by recording the data of these base stations.Through analyzing the data of different business circle based on feature extraction and comparing different business circle category characteristics, which can choose a suitable area for operators of commercial marketing.

  12. Scope-Based Method Cache Analysis

    DEFF Research Database (Denmark)

    Huber, Benedikt; Hepp, Stefan; Schoeberl, Martin

    2014-01-01

    , as it requests memory transfers at well-defined instructions only. In this article, we present a new cache analysis framework that generalizes and improves work on cache persistence analysis. The analysis demonstrates that a global view on the cache behavior permits the precise analyses of caches which are hard......The quest for time-predictable systems has led to the exploration of new hardware architectures that simplify analysis and reasoning in the temporal domain, while still providing competitive performance. For the instruction memory, the method cache is a conceptually attractive solution...

  13. Canonical analysis based on mutual information

    DEFF Research Database (Denmark)

    Nielsen, Allan Aasbjerg; Vestergaard, Jacob Schack

    2015-01-01

    combinations with the information theoretical measure mutual information (MI). We term this type of analysis canonical information analysis (CIA). MI allows for the actual joint distribution of the variables involved and not just second order statistics. While CCA is ideal for Gaussian data, CIA facilitates...

  14. Using Willie's Acid-Base Box for Blood Gas Analysis

    Science.gov (United States)

    Dietz, John R.

    2011-01-01

    In this article, the author describes a method developed by Dr. William T. Lipscomb for teaching blood gas analysis of acid-base status and provides three examples using Willie's acid-base box. Willie's acid-base box is constructed using three of the parameters of standard arterial blood gas analysis: (1) pH; (2) bicarbonate; and (3) CO[subscript…

  15. Dynamic Chest Image Analysis: Evaluation of Model-Based Pulmonary Perfusion Analysis With Pyramid Images

    National Research Council Canada - National Science Library

    Liang, Jianming

    2001-01-01

    Dynamic Chest Image Analysis aims to develop model-based computer analysis and visualization methods for showing focal and general abnormalities of lung ventilation and perfusion based on a sequence...

  16. Phosphoproteomic Profiling Reveals Epstein-Barr Virus Protein Kinase Integration of DNA Damage Response and Mitotic Signaling.

    Directory of Open Access Journals (Sweden)

    Renfeng Li

    2015-12-01

    Full Text Available Epstein-Barr virus (EBV is etiologically linked to infectious mononucleosis and several human cancers. EBV encodes a conserved protein kinase BGLF4 that plays a key role in the viral life cycle. To provide new insight into the host proteins regulated by BGLF4, we utilized stable isotope labeling by amino acids in cell culture (SILAC-based quantitative proteomics to compare site-specific phosphorylation in BGLF4-expressing Akata B cells. Our analysis revealed BGLF4-mediated hyperphosphorylation of 3,046 unique sites corresponding to 1,328 proteins. Frequency analysis of these phosphosites revealed a proline-rich motif signature downstream of BGLF4, indicating a broader substrate recognition for BGLF4 than its cellular ortholog cyclin-dependent kinase 1 (CDK1. Further, motif analysis of the hyperphosphorylated sites revealed enrichment in ATM, ATR and Aurora kinase substrates while functional analyses revealed significant enrichment of pathways related to the DNA damage response (DDR, mitosis and cell cycle. Phosphorylation of proteins associated with the mitotic spindle assembly checkpoint (SAC indicated checkpoint activation, an event that inactivates the anaphase promoting complex/cyclosome, APC/C. Furthermore, we demonstrated that BGLF4 binds to and directly phosphorylates the key cellular proteins PP1, MPS1 and CDC20 that lie upstream of SAC activation and APC/C inhibition. Consistent with APC/C inactivation, we found that BGLF4 stabilizes the expression of many known APC/C substrates. We also noted hyperphosphorylation of 22 proteins associated the nuclear pore complex, which may contribute to nuclear pore disassembly and SAC activation. A drug that inhibits mitotic checkpoint activation also suppressed the accumulation of extracellular EBV virus. Taken together, our data reveal that, in addition to the DDR, manipulation of mitotic kinase signaling and SAC activation are mechanisms associated with lytic EBV replication. All MS data have been

  17. A Comprehensive Transcriptomic and Proteomic Analysis of Hydra Head Regeneration.

    Science.gov (United States)

    Petersen, Hendrik O; Höger, Stefanie K; Looso, Mario; Lengfeld, Tobias; Kuhn, Anne; Warnken, Uwe; Nishimiya-Fujisawa, Chiemi; Schnölzer, Martina; Krüger, Marcus; Özbek, Suat; Simakov, Oleg; Holstein, Thomas W

    2015-08-01

    The cnidarian freshwater polyp Hydra sp. exhibits an unparalleled regeneration capacity in the animal kingdom. Using an integrative transcriptomic and stable isotope labeling by amino acids in cell culture proteomic/phosphoproteomic approach, we studied stem cell-based regeneration in Hydra polyps. As major contributors to head regeneration, we identified diverse signaling pathways adopted for the regeneration response as well as enriched novel genes. Our global analysis reveals two distinct molecular cascades: an early injury response and a subsequent, signaling driven patterning of the regenerating tissue. A key factor of the initial injury response is a general stabilization of proteins and a net upregulation of transcripts, which is followed by a subsequent activation cascade of signaling molecules including Wnts and transforming growth factor (TGF) beta-related factors. We observed moderate overlap between the factors contributing to proteomic and transcriptomic responses suggesting a decoupled regulation between the transcriptional and translational levels. Our data also indicate that interstitial stem cells and their derivatives (e.g., neurons) have no major role in Hydra head regeneration. Remarkably, we found an enrichment of evolutionarily more recent genes in the early regeneration response, whereas conserved genes are more enriched in the late phase. In addition, genes specific to the early injury response were enriched in transposon insertions. Genetic dynamicity and taxon-specific factors might therefore play a hitherto underestimated role in Hydra regeneration. © The Author 2015. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

  18. Quantitative Phosphoproteomics after Auxin-stimulated Lateral Root Induction Identifies an SNX1 Protein Phosphorylation Site Required for Growth*

    Science.gov (United States)

    Zhang, Hongtao; Zhou, Houjiang; Berke, Lidija; Heck, Albert J. R.; Mohammed, Shabaz; Scheres, Ben; Menke, Frank L. H.

    2013-01-01

    Protein phosphorylation is instrumental to early signaling events. Studying system-wide phosphorylation in relation to processes under investigation requires a quantitative proteomics approach. In Arabidopsis, auxin application can induce pericycle cell divisions and lateral root formation. Initiation of lateral root formation requires transcriptional reprogramming following auxin-mediated degradation of transcriptional repressors. The immediate early signaling events prior to this derepression are virtually uncharacterized. To identify the signal molecules responding to auxin application, we used a lateral root-inducible system that was previously developed to trigger synchronous division of pericycle cells. To identify and quantify the early signaling events following this induction, we combined 15N-based metabolic labeling and phosphopeptide enrichment and applied a mass spectrometry-based approach. In total, 3068 phosphopeptides were identified from auxin-treated root tissue. This root proteome dataset contains largely phosphopeptides not previously reported and represents one of the largest quantitative phosphoprotein datasets from Arabidopsis to date. Key proteins responding to auxin treatment included the multidrug resistance-like and PIN2 auxin carriers, AUXIN RESPONSE FACTOR2 (ARF2), SUPPRESSOR OF AUXIN RESISTANCE 3 (SAR3), and SORTING NEXIN1 (SNX1). Mutational analysis of serine 16 of SNX1 showed that overexpression of the mutated forms of SNX1 led to retarded growth and reduction of lateral root formation due to the reduced outgrowth of the primordium, showing proof of principle for our approach. PMID:23328941

  19. Quantitative phosphoproteomics after auxin-stimulated lateral root induction identifies an SNX1 protein phosphorylation site required for growth.

    Science.gov (United States)

    Zhang, Hongtao; Zhou, Houjiang; Berke, Lidija; Heck, Albert J R; Mohammed, Shabaz; Scheres, Ben; Menke, Frank L H

    2013-05-01

    Protein phosphorylation is instrumental to early signaling events. Studying system-wide phosphorylation in relation to processes under investigation requires a quantitative proteomics approach. In Arabidopsis, auxin application can induce pericycle cell divisions and lateral root formation. Initiation of lateral root formation requires transcriptional reprogramming following auxin-mediated degradation of transcriptional repressors. The immediate early signaling events prior to this derepression are virtually uncharacterized. To identify the signal molecules responding to auxin application, we used a lateral root-inducible system that was previously developed to trigger synchronous division of pericycle cells. To identify and quantify the early signaling events following this induction, we combined (15)N-based metabolic labeling and phosphopeptide enrichment and applied a mass spectrometry-based approach. In total, 3068 phosphopeptides were identified from auxin-treated root tissue. This root proteome dataset contains largely phosphopeptides not previously reported and represents one of the largest quantitative phosphoprotein datasets from Arabidopsis to date. Key proteins responding to auxin treatment included the multidrug resistance-like and PIN2 auxin carriers, auxin response factor2 (ARF2), suppressor of auxin resistance 3 (SAR3), and sorting nexin1 (SNX1). Mutational analysis of serine 16 of SNX1 showed that overexpression of the mutated forms of SNX1 led to retarded growth and reduction of lateral root formation due to the reduced outgrowth of the primordium, showing proof of principle for our approach.

  20. Web Based Distributed Coastal Image Analysis System, Phase I

    Data.gov (United States)

    National Aeronautics and Space Administration — This project develops Web based distributed image analysis system processing the Moderate Resolution Imaging Spectroradiometer (MODIS) data to provide decision...

  1. Description-based and experience-based decisions: individual analysis

    Directory of Open Access Journals (Sweden)

    Andrey Kudryavtsev

    2012-05-01

    Full Text Available We analyze behavior in two basic classes of decision tasks: description-based and experience-based. In particular, we compare the prediction power of a number of decision learning models in both kinds of tasks. Unlike most previous studies, we focus on individual, rather than aggregate, behavioral characteristics. We carry out an experiment involving a battery of both description- and experience-based choices between two mixed binary prospects made by each of the participants, and employ a number of formal models for explaining and predicting participants' choices: Prospect theory (PT (Kahneman and Tversky, 1979; Expectancy-Valence model (EVL (Busemeyer and Stout, 2002; and three combinations of these well-established models. We document that the PT and the EVL models are best for predicting people's decisions in description- and experience-based tasks, respectively, which is not surprising as these two models are designed specially for these kinds of tasks. Furthermore, we find that models involving linear weighting of gains and losses perform better in both kinds of tasks, from the point of view of generalizability and individual parameter consistency. We therefore, conclude that, overall, when both prospects are mixed, the assumption of diminishing sensitivity does not improve models' prediction power for individual decision-makers. Finally, for some of the models' parameters, we document consistency at the individual level between description- and experience-based tasks.

  2. M-X Basing Area Analysis Process

    National Research Council Canada - National Science Library

    1980-01-01

    ... or unreasonable basing areas for the M-X missile in multiple protective structures (MPS). The process began in January 1977 with criteria involving geotechnical, cultural, safety and other concerns...

  3. Environmentally based Cost-Benefit Analysis

    International Nuclear Information System (INIS)

    Magnell, M.

    1993-11-01

    The fundamentals of the basic elements of a new comprehensive economic assessment, MILA, developed in Sweden with inspiration from the Total Cost Assessment-model are presented. The core of the MILA approach is an expanded cost and benefit inventory. But MILA also includes a complementary addition of an internal waste stream analysis, a tool for evaluation of environmental conflicts in monetary terms, an extended time horizon and direct allocation of costs and revenues to products and processes. However, MILA does not ensure profitability for environmentally sound projects. Essentially, MILA is an approach of refining investment and profitability analysis of a project, investment or product. 109 refs., 38 figs

  4. Epoch-based analysis of speech signals

    Indian Academy of Sciences (India)

    It is shown that knowledge of epochs can be used for analysis of speech for glottal activity detection, extrac- ..... The performance of the proposed GAD method was evaluated using the detection error trade- off (DET) curves ..... the oral closure is released more or less impulsively as the vocal tract moves towards a configu-.

  5. ANALYSIS OF A DATA BASE OF CHALCOPYRITE ...

    African Journals Online (AJOL)

    Université Aboubekr Belkaid de Tlemcen, Faculté des sciences, Département de physique, Unité de Recherche sur les Matériaux Energies Renouvelables, B.P 119,. 13000 Tlemcen Algerie. Received: 15 November 2011 / Accepted: 27 December 2011 / Published online: 31 December 2011. ABSTRACT. The analysis of ...

  6. Competence-based employability: A Rasch analysis

    NARCIS (Netherlands)

    Fröhlich, D.; Liu, M.; van der Heijden, B.

    2015-01-01

    Due to trends such as increasingly inter-organizational careers, the concept of employability is high on the agenda of employees, employers, and pol icy makers. To improve our understanding of this concept, we need to understand thoroughly its measurement. We performed a Rasch analysis of Van der

  7. Epoch-based analysis of speech signals

    Indian Academy of Sciences (India)

    Epoch sequence is useful to manipulate prosody in speech synthesis applications. Accurate estimation of epochs helps in characterizing voice quality features. Epoch extraction also helps in speech enhancement and multispeaker separation. In this tutorial article, the importance of epochs for speech analysis is discussed, ...

  8. Model Based Analysis of Insider Threats

    DEFF Research Database (Denmark)

    Chen, Taolue; Han, Tingting; Kammueller, Florian

    2016-01-01

    In order to detect malicious insider attacks it is important to model and analyse infrastructures and policies of organisations and the insiders acting within them. We extend formal approaches that allow modelling such scenarios by quantitative aspects to enable a precise analysis of security...

  9. Movement Pattern Analysis Based on Sequence Signatures

    Directory of Open Access Journals (Sweden)

    Seyed Hossein Chavoshi

    2015-09-01

    Full Text Available Increased affordability and deployment of advanced tracking technologies have led researchers from various domains to analyze the resulting spatio-temporal movement data sets for the purpose of knowledge discovery. Two different approaches can be considered in the analysis of moving objects: quantitative analysis and qualitative analysis. This research focuses on the latter and uses the qualitative trajectory calculus (QTC, a type of calculus that represents qualitative data on moving point objects (MPOs, and establishes a framework to analyze the relative movement of multiple MPOs. A visualization technique called sequence signature (SESI is used, which enables to map QTC patterns in a 2D indexed rasterized space in order to evaluate the similarity of relative movement patterns of multiple MPOs. The applicability of the proposed methodology is illustrated by means of two practical examples of interacting MPOs: cars on a highway and body parts of a samba dancer. The results show that the proposed method can be effectively used to analyze interactions of multiple MPOs in different domains.

  10. A Goal based methodology for HAZOP analysis

    DEFF Research Database (Denmark)

    Rossing, Netta Liin; Lind, Morten; Jensen, Niels

    2010-01-01

    This paper presents a goal based methodology for HAZOP studies in which a functional model of the plant is used to assist in a functional decomposition of the plant starting from the purpose of the plant and continuing down to the function of a single node, e.g. a pipe section. This approach lead...

  11. Automated Video-Based Traffic Count Analysis.

    Science.gov (United States)

    2016-01-01

    The goal of this effort has been to develop techniques that could be applied to the : detection and tracking of vehicles in overhead footage of intersections. To that end we : have developed and published techniques for vehicle tracking based on dete...

  12. Analysis of Financial Position Based on the Balance Sheet

    OpenAIRE

    Spineanu-Georgescu Luciana

    2011-01-01

    Analysis of financial position based on the balance sheet is mainly aimed at assessing the extent to which financial structure chosen by the firm, namely, financial resources, covering the needs reflected in the balance sheet financed. This is done through an analysis known as horizontal analysis balance sheet financial imbalances.

  13. Desiccant-Based Preconditioning Market Analysis

    Energy Technology Data Exchange (ETDEWEB)

    Fischer, J.

    2001-01-11

    A number of important conclusions can be drawn as a result of this broad, first-phase market evaluation. The more important conclusions include the following: (1) A very significant market opportunity will exist for specialized outdoor air-handling units (SOAHUs) as more construction and renovation projects are designed to incorporate the recommendations made by the ASHRAE 62-1989 standard. Based on this investigation, the total potential market is currently $725,000,000 annually (see Table 6, Sect. 3). Based on the market evaluations completed, it is estimated that approximately $398,000,000 (55%) of this total market could be served by DBC systems if they were made cost-effective through mass production. Approximately $306,000,000 (42%) of the total can be served by a non-regenerated, desiccant-based total recovery approach, based on the information provided by this investigation. Approximately $92,000,000 (13%) can be served by a regenerated desiccant-based cooling approach (see Table 7, Sect. 3). (2) A projection of the market selling price of various desiccant-based SOAHU systems was prepared using prices provided by Trane for central-station, air-handling modules currently manufactured. The wheel-component pricing was added to these components by SEMCO. This resulted in projected pricing for these systems that is significantly less than that currently offered by custom suppliers (see Table 4, Sect. 2). Estimated payback periods for all SOAHU approaches were quite short when compared with conventional over-cooling and reheat systems. Actual paybacks may vary significantly depending on site-specific considerations. (3) In comparing cost vs benefit of each SOAHU approach, it is critical that the total system design be evaluated. For example, the cost premium of a DBC system is very significant when compared to a conventional air handling system, yet the reduced chiller, boiler, cooling tower, and other expense often equals or exceeds this premium, resulting in a

  14. CrossCheck: an open-source web tool for high-throughput screen data analysis.

    Science.gov (United States)

    Najafov, Jamil; Najafov, Ayaz

    2017-07-19

    Modern high-throughput screening methods allow researchers to generate large datasets that potentially contain important biological information. However, oftentimes, picking relevant hits from such screens and generating testable hypotheses requires training in bioinformatics and the skills to efficiently perform database mining. There are currently no tools available to general public that allow users to cross-reference their screen datasets with published screen datasets. To this end, we developed CrossCheck, an online platform for high-throughput screen data analysis. CrossCheck is a centralized database that allows effortless comparison of the user-entered list of gene symbols with 16,231 published datasets. These datasets include published data from genome-wide RNAi and CRISPR screens, interactome proteomics and phosphoproteomics screens, cancer mutation databases, low-throughput studies of major cell signaling mediators, such as kinases, E3 ubiquitin ligases and phosphatases, and gene ontological information. Moreover, CrossCheck includes a novel database of predicted protein kinase substrates, which was developed using proteome-wide consensus motif searches. CrossCheck dramatically simplifies high-throughput screen data analysis and enables researchers to dig deep into the published literature and streamline data-driven hypothesis generation. CrossCheck is freely accessible as a web-based application at http://proteinguru.com/crosscheck.

  15. SH2 Superbinder Modified Monolithic Capillary Column for the Sensitive Analysis of Protein Tyrosine Phosphorylation.

    Science.gov (United States)

    Yao, Yating; Bian, Yangyang; Dong, Mingming; Wang, Yan; Lv, Jiawen; Chen, Lianfang; Wang, Hongwei; Mao, Jiawei; Dong, Jing; Ye, Mingliang

    2018-01-05

    In this study, we present a method to specifically capture phosphotyrosine (pTyr) peptides from minute amount of sample for the sensitive analysis of protein tyrosine phosphorylation. We immobilized SH2 superbinder on a monolithic capillary column to construct a microreactor to enrich pTyr peptides. It was found that the synthetic pTyr peptide could be specifically enriched by the microreactor from the peptide mixture prepared by spiking of the synthetic pTyr peptide into the tryptic digests of α-casein and β-casein with molar ratios of 1:1000:1000. The microreactor was further applied to enrich pTyr peptides from pervanadate-treated HeLa cell digests for phosphoproteomics analysis, which resulted in the identification of 796 unique pTyr sites. In contrast, the conventional SH2 superbinder-based method identified 41 pTyr sites for the same sample, only 5.2% of the number achieved by the microreactor. Finally, this microreactor was also applied to analyze the pTyr in Shc1 complex, an immunopurified protein complex, which resulted in the identification of 15 pTyr sites. Together, this technique is best fitted to analyze the pTyr in minute amount of sample and will have broad application in fields where only a limited amount of sample is available.

  16. Global analysis of protein expression and phosphorylation of three stages of Plasmodium falciparum intraerythrocytic development.

    Science.gov (United States)

    Pease, Brittany N; Huttlin, Edward L; Jedrychowski, Mark P; Talevich, Eric; Harmon, John; Dillman, Timothy; Kannan, Natarajan; Doerig, Christian; Chakrabarti, Ratna; Gygi, Steven P; Chakrabarti, Debopam

    2013-09-06

    During asexual intraerythrocytic development, Plasmodium falciparum diverges from the paradigm of the eukaryotic cell cycles by undergoing multiple rounds of DNA replication and nuclear division without cytokinesis. A better understanding of the molecular switches that coordinate a myriad of events for the progression of the parasite through the intraerythrocytic developmental stages will be of fundamental importance for rational design of intervention strategies. To achieve this goal, we performed isobaric tag-based quantitative proteomics and phosphoproteomics analyses of three developmental stages in the Plasmodium asexual cycle and identified 2767 proteins, 1337 phosphoproteins, and 6293 phosphorylation sites. Approximately 34% of identified proteins and 75% of phosphorylation sites exhibit changes in abundance as the intraerythrocytic cycle progresses. Our study identified 43 distinct phosphorylation motifs and a range of potential MAPK/CDK substrates. Further analysis of phosphorylated kinases identified 30 protein kinases with 126 phosphorylation sites within the kinase domain or in N- or C-terminal tails. Many of these phosphorylations are likely CK2-mediated. We define the constitutive and regulated expression of the Plasmodium proteome during the intraerythrocytic developmental cycle, offering an insight into the dynamics of phosphorylation during asexual cycle progression. Our system-wide comprehensive analysis is a major step toward defining kinase-substrate pairs operative in various signaling networks in the parasite.

  17. Knowledge-based analysis of phenotypes

    KAUST Repository

    Hoendorf, Robert

    2016-01-27

    Phenotypes are the observable characteristics of an organism, and they are widely recorded in biology and medicine. To facilitate data integration, ontologies that formally describe phenotypes are being developed in several domains. I will describe a formal framework to describe phenotypes. A formalized theory of phenotypes is not only useful for domain analysis, but can also be applied to assist in the diagnosis of rare genetic diseases, and I will show how our results on the ontology of phenotypes is now applied in biomedical research.

  18. Discretization analysis of bifurcation based nonlinear amplifiers

    Science.gov (United States)

    Feldkord, Sven; Reit, Marco; Mathis, Wolfgang

    2017-09-01

    Recently, for modeling biological amplification processes, nonlinear amplifiers based on the supercritical Andronov-Hopf bifurcation have been widely analyzed analytically. For technical realizations, digital systems have become the most relevant systems in signal processing applications. The underlying continuous-time systems are transferred to the discrete-time domain using numerical integration methods. Within this contribution, effects on the qualitative behavior of the Andronov-Hopf bifurcation based systems concerning numerical integration methods are analyzed. It is shown exemplarily that explicit Runge-Kutta methods transform the truncated normalform equation of the Andronov-Hopf bifurcation into the normalform equation of the Neimark-Sacker bifurcation. Dependent on the order of the integration method, higher order terms are added during this transformation.A rescaled normalform equation of the Neimark-Sacker bifurcation is introduced that allows a parametric design of a discrete-time system which corresponds to the rescaled Andronov-Hopf system. This system approximates the characteristics of the rescaled Hopf-type amplifier for a large range of parameters. The natural frequency and the peak amplitude are preserved for every set of parameters. The Neimark-Sacker bifurcation based systems avoid large computational effort that would be caused by applying higher order integration methods to the continuous-time normalform equations.

  19. Discretization analysis of bifurcation based nonlinear amplifiers

    Directory of Open Access Journals (Sweden)

    S. Feldkord

    2017-09-01

    Full Text Available Recently, for modeling biological amplification processes, nonlinear amplifiers based on the supercritical Andronov–Hopf bifurcation have been widely analyzed analytically. For technical realizations, digital systems have become the most relevant systems in signal processing applications. The underlying continuous-time systems are transferred to the discrete-time domain using numerical integration methods. Within this contribution, effects on the qualitative behavior of the Andronov–Hopf bifurcation based systems concerning numerical integration methods are analyzed. It is shown exemplarily that explicit Runge–Kutta methods transform the truncated normalform equation of the Andronov–Hopf bifurcation into the normalform equation of the Neimark–Sacker bifurcation. Dependent on the order of the integration method, higher order terms are added during this transformation.A rescaled normalform equation of the Neimark–Sacker bifurcation is introduced that allows a parametric design of a discrete-time system which corresponds to the rescaled Andronov–Hopf system. This system approximates the characteristics of the rescaled Hopf-type amplifier for a large range of parameters. The natural frequency and the peak amplitude are preserved for every set of parameters. The Neimark–Sacker bifurcation based systems avoid large computational effort that would be caused by applying higher order integration methods to the continuous-time normalform equations.

  20. Pathway-based analysis tools for complex diseases: a review.

    Science.gov (United States)

    Jin, Lv; Zuo, Xiao-Yu; Su, Wei-Yang; Zhao, Xiao-Lei; Yuan, Man-Qiong; Han, Li-Zhen; Zhao, Xiang; Chen, Ye-Da; Rao, Shao-Qi

    2014-10-01

    Genetic studies are traditionally based on single-gene analysis. The use of these analyses can pose tremendous challenges for elucidating complicated genetic interplays involved in complex human diseases. Modern pathway-based analysis provides a technique, which allows a comprehensive understanding of the molecular mechanisms underlying complex diseases. Extensive studies utilizing the methods and applications for pathway-based analysis have significantly advanced our capacity to explore large-scale omics data, which has rapidly accumulated in biomedical fields. This article is a comprehensive review of the pathway-based analysis methods-the powerful methods with the potential to uncover the biological depths of the complex diseases. The general concepts and procedures for the pathway-based analysis methods are introduced and then, a comprehensive review of the major approaches for this analysis is presented. In addition, a list of available pathway-based analysis software and databases is provided. Finally, future directions and challenges for the methodological development and applications of pathway-based analysis techniques are discussed. This review will provide a useful guide to dissect complex diseases. Copyright © 2014 The Authors. Production and hosting by Elsevier Ltd.. All rights reserved.

  1. Physical-Mechanisms Based Reliability Analysis For Emerging Technologies

    Science.gov (United States)

    2017-05-05

    AFRL-AFOSR-VA-TR-2017-0095 PHYSICAL -MECHANISMS BASED RELIABILITY ANALYSIS FOR EMERGING TECHNOLOGIES Ron Schrimpf VANDERBILT UNIVERSITY 110 21ST...SUBTITLE PHYSICAL -MECHANISMS BASED RELIABILITY ANALYSIS FOR EMERGING TECHNOLOGIES 5a.  CONTRACT NUMBER 5b.  GRANT NUMBER FA9550-11-1-0307 5c.  PROGRAM...which reliability models can be built. Thus, it is important to develop more predictive reliability models for advanced technologies, based on physical

  2. Spatial analysis and modelling based on activities

    CSIR Research Space (South Africa)

    Conradie, Dirk CU

    2010-01-01

    Full Text Available of the year where visibility on the road near sunrise and sunset would be severely impaired, possibly contributing to accidents. One of the advantages of a visual based simulation is that non-technical role players can visualise problems and it enables them... to work with professional, scientific and technical designers. The vector graphic part of the simulation environment can be conveniently built by means of standard CAD programs such as AutoCAD, AutoDesk Revit, 3D Studio Max or MicroGDS. Although...

  3. Sandia National Laboratories analysis code data base

    Energy Technology Data Exchange (ETDEWEB)

    Peterson, C.W.

    1994-11-01

    Sandia National Laboratories, mission is to solve important problems in the areas of national defense, energy security, environmental integrity, and industrial technology. The Laboratories` strategy for accomplishing this mission is to conduct research to provide an understanding of the important physical phenomena underlying any problem, and then to construct validated computational models of the phenomena which can be used as tools to solve the problem. In the course of implementing this strategy, Sandia`s technical staff has produced a wide variety of numerical problem-solving tools which they use regularly in the design, analysis, performance prediction, and optimization of Sandia components, systems and manufacturing processes. This report provides the relevant technical and accessibility data on the numerical codes used at Sandia, including information on the technical competency or capability area that each code addresses, code ``ownership`` and release status, and references describing the physical models and numerical implementation.

  4. Network Anomaly Detection Based on Wavelet Analysis

    Directory of Open Access Journals (Sweden)

    Ali A. Ghorbani

    2008-11-01

    Full Text Available Signal processing techniques have been applied recently for analyzing and detecting network anomalies due to their potential to find novel or unknown intrusions. In this paper, we propose a new network signal modelling technique for detecting network anomalies, combining the wavelet approximation and system identification theory. In order to characterize network traffic behaviors, we present fifteen features and use them as the input signals in our system. We then evaluate our approach with the 1999 DARPA intrusion detection dataset and conduct a comprehensive analysis of the intrusions in the dataset. Evaluation results show that the approach achieves high-detection rates in terms of both attack instances and attack types. Furthermore, we conduct a full day's evaluation in a real large-scale WiFi ISP network where five attack types are successfully detected from over 30 millions flows.

  5. Network reliability analysis based on percolation theory

    International Nuclear Information System (INIS)

    Li, Daqing; Zhang, Qiong; Zio, Enrico; Havlin, Shlomo; Kang, Rui

    2015-01-01

    In this paper, we propose a new way of looking at the reliability of a network using percolation theory. In this new view, a network failure can be regarded as a percolation process and the critical threshold of percolation can be used as network failure criterion linked to the operational settings under control. To demonstrate our approach, we consider both random network models and real networks with different nodes and/or edges lifetime distributions. We study numerically and theoretically the network reliability and find that the network reliability can be solved as a voting system with threshold given by percolation theory. Then we find that the average lifetime of random network increases linearly with the average lifetime of its nodes with uniform life distributions. Furthermore, the average lifetime of the network becomes saturated when system size is increased. Finally, we demonstrate our method on the transmission network system of IEEE 14 bus. - Highlights: • Based on percolation theory, we address questions of practical interest such as “how many failed nodes/edges will break down the whole network?” • The percolation threshold naturally gives a network failure criterion. • The approach based on percolation theory is suited for calculations of large-scale networks

  6. The Route Analysis Based On Flight Plan

    Science.gov (United States)

    Feriyanto, Nur; Saleh, Chairul; Fauzi, Achmad; Rachman Dzakiyullah, Nur; Riza Iwaputra, Kahfi

    2016-02-01

    Economic development effects use of air transportation since the business process in every aspect was increased. Many people these days was prefer using airplane because it can save time and money. This situation also effects flight routes, many airlines offer new routes to deal with competition. Managing flight routes is one of the problems that must be faced in order to find the efficient and effective routes. This paper investigates the best routes based on flight performance by determining the amount of block fuel for the Jakarta-Denpasar flight route. Moreover, in this work compares a two kinds of aircraft and tracks by calculating flight distance, flight time and block fuel. The result shows Jakarta-Denpasar in the Track II has effective and efficient block fuel that can be performed by Airbus 320-200 aircraft. This study can contribute to practice in making an effective decision, especially helping executive management of company due to selecting appropriate aircraft and the track in the flight plan based on the block fuel consumption for business operation.

  7. Model-Based Analysis of Hand Radiographs

    Science.gov (United States)

    Levitt, Tod S.; Hedgcock, Marcus W.

    1989-05-01

    As a step toward computer assisted imagery interpretation, we are developing algorithms for computed radiography that allow a computer to recognize specific bones and joints, and to identify variations from normal in size, shape and density. In this paper we report on our approach to model-based computer recognition of hands in radiographs. First, image processing hypotheses of the imaged bones. Multiple hypotheses of the size and orientation of the imaged anatomy are matched against stored 3D models fof the relevant bones, obtained from statistically valid populations studies. Probabilities of the hypotheses are accrued using Bayesian inference techniques whose evaluation is guided by the structure of the hand model and the observed image-derived evidence such as anti-parallel edges, local contrast, etc. High probability matches between the hand model and the image data can cue additional image processing-based ssearch for bones, joints and soft-tissue to confirm hypotheses of the location of the imaged hand. At this point multipule disease detection techniques, automated bone age identification, etc. can be employed.

  8. Image based SAR product simulation for analysis

    Science.gov (United States)

    Domik, G.; Leberl, F.

    1987-01-01

    SAR product simulation serves to predict SAR image gray values for various flight paths. Input typically consists of a digital elevation model and backscatter curves. A new method is described of product simulation that employs also a real SAR input image for image simulation. This can be denoted as 'image-based simulation'. Different methods to perform this SAR prediction are presented and advantages and disadvantages discussed. Ascending and descending orbit images from NASA's SIR-B experiment were used for verification of the concept: input images from ascending orbits were converted into images from a descending orbit; the results are compared to the available real imagery to verify that the prediction technique produces meaningful image data.

  9. Network analysis based on large deviation statistics

    Science.gov (United States)

    Miyazaki, Syuji

    2007-07-01

    A chaotic piecewise linear map whose statistical properties are identical to those of a random walk on directed graphs such as the world wide web (WWW) is constructed, and the dynamic quantity is analyzed in the framework of large deviation statistics. Gibbs measures include the weight factor appearing in the weighted average of the dynamic quantity, which can also quantitatively measure the importance of web sites. Currently used levels of importance in the commercial search engines are independent of search terms, which correspond to the stationary visiting frequency of each node obtained from a random walk on the network or equivalent chaotic dynamics. Levels of importance based on the Gibbs measure depend on each search term which is specified by the searcher. The topological conjugate transformation between one dynamical system with a Gibbs measure and another dynamical system whose standard invariant probability measure is identical to the Gibbs measure is also discussed.

  10. Network-based analysis of complex diseases.

    Science.gov (United States)

    Liu, Z-P; Wang, Y; Zhang, X-S; Chen, L

    2012-02-01

    Complex diseases are commonly believed to be caused by the breakdown of several correlated genes rather than individual genes. The availability of genome-wide data of high-throughput experiments provides us with new opportunity to explore this hypothesis by analysing the disease-related biomolecular networks, which are expected to bridge genotypes and disease phenotypes and further reveal the biological mechanisms of complex diseases. In this study, the authors review the existing network biology efforts to study complex diseases, such as breast cancer, diabetes and Alzheimer's disease, using high-throughput data and computational tools. Specifically, the authors categorise these existing methods into several classes based on the research topics, that is, disease genes, dysfunctional pathways, network signatures and drug-target networks. The authors also summarise the pros and cons of those methods from both computation and application perspectives, and further discuss research trends and future topics of this promising field.

  11. Radiometer Design Analysis Based Upon Measurement Uncertainty

    Science.gov (United States)

    Racette, Paul E.; Lang, Roger H.

    2004-01-01

    This paper introduces a method for predicting the performance of a radiometer design based on calculating the measurement uncertainty. The variety in radiometer designs and the demand for improved radiometric measurements justify the need for a more general and comprehensive method to assess system performance. Radiometric resolution, or sensitivity, is a figure of merit that has been commonly used to characterize the performance of a radiometer. However when evaluating the performance of a calibration design for a radiometer, the use of radiometric resolution has limited application. These limitations are overcome by considering instead the measurement uncertainty. A method for calculating measurement uncertainty for a generic radiometer design including its calibration algorithm is presented. The result is a generalized technique by which system calibration architectures and design parameters can be studied to optimize instrument performance for given requirements and constraints. Example applications demonstrate the utility of using measurement uncertainty as a figure of merit.

  12. Analysis of Vehicle-Based Security Operations

    Energy Technology Data Exchange (ETDEWEB)

    Carter, Jason M [ORNL; Paul, Nate R [ORNL

    2015-01-01

    Vehicle-to-vehicle (V2V) communications promises to increase roadway safety by providing each vehicle with 360 degree situational awareness of other vehicles in proximity, and by complementing onboard sensors such as radar or camera in detecting imminent crash scenarios. In the United States, approximately three hundred million automobiles could participate in a fully deployed V2V system if Dedicated Short-Range Communication (DSRC) device use becomes mandatory. The system s reliance on continuous communication, however, provides a potential means for unscrupulous persons to transmit false data in an attempt to cause crashes, create traffic congestion, or simply render the system useless. V2V communications must be highly scalable while retaining robust security and privacy preserving features to meet the intra-vehicle and vehicle-to-infrastructure communication requirements for a growing vehicle population. Oakridge National Research Laboratory is investigating a Vehicle-Based Security System (VBSS) to provide security and privacy for a fully deployed V2V and V2I system. In the VBSS an On-board Unit (OBU) generates short-term certificates and signs Basic Safety Messages (BSM) to preserve privacy and enhance security. This work outlines a potential VBSS structure and its operational concepts; it examines how a vehicle-based system might feasibly provide security and privacy, highlights remaining challenges, and explores potential mitigations to address those challenges. Certificate management alternatives that attempt to meet V2V security and privacy requirements have been examined previously by the research community including privacy-preserving group certificates, shared certificates, and functional encryption. Due to real-world operational constraints, adopting one of these approaches for VBSS V2V communication is difficult. Timely misbehavior detection and revocation are still open problems for any V2V system. We explore the alternative approaches that may be

  13. Model Based Analysis and Test Generation for Flight Software

    Science.gov (United States)

    Pasareanu, Corina S.; Schumann, Johann M.; Mehlitz, Peter C.; Lowry, Mike R.; Karsai, Gabor; Nine, Harmon; Neema, Sandeep

    2009-01-01

    We describe a framework for model-based analysis and test case generation in the context of a heterogeneous model-based development paradigm that uses and combines Math- Works and UML 2.0 models and the associated code generation tools. This paradigm poses novel challenges to analysis and test case generation that, to the best of our knowledge, have not been addressed before. The framework is based on a common intermediate representation for different modeling formalisms and leverages and extends model checking and symbolic execution tools for model analysis and test case generation, respectively. We discuss the application of our framework to software models for a NASA flight mission.

  14. Analysis of composition-based metagenomic classification.

    Science.gov (United States)

    Higashi, Susan; Barreto, André da Motta Salles; Cantão, Maurício Egidio; de Vasconcelos, Ana Tereza Ribeiro

    2012-01-01

    An essential step of a metagenomic study is the taxonomic classification, that is, the identification of the taxonomic lineage of the organisms in a given sample. The taxonomic classification process involves a series of decisions. Currently, in the context of metagenomics, such decisions are usually based on empirical studies that consider one specific type of classifier. In this study we propose a general framework for analyzing the impact that several decisions can have on the classification problem. Instead of focusing on any specific classifier, we define a generic score function that provides a measure of the difficulty of the classification task. Using this framework, we analyze the impact of the following parameters on the taxonomic classification problem: (i) the length of n-mers used to encode the metagenomic sequences, (ii) the similarity measure used to compare sequences, and (iii) the type of taxonomic classification, which can be conventional or hierarchical, depending on whether the classification process occurs in a single shot or in several steps according to the taxonomic tree. We defined a score function that measures the degree of separability of the taxonomic classes under a given configuration induced by the parameters above. We conducted an extensive computational experiment and found out that reasonable values for the parameters of interest could be (i) intermediate values of n, the length of the n-mers; (ii) any similarity measure, because all of them resulted in similar scores; and (iii) the hierarchical strategy, which performed better in all of the cases. As expected, short n-mers generate lower configuration scores because they give rise to frequency vectors that represent distinct sequences in a similar way. On the other hand, large values for n result in sparse frequency vectors that represent differently metagenomic fragments that are in fact similar, also leading to low configuration scores. Regarding the similarity measure, in

  15. A modified principal component analysis-based utility theory ...

    African Journals Online (AJOL)

    user

    modified PCA-based utility theory (UT) approach for optimization of correlated responses. ... Keywords: EDM; Correlated responses; Optimization; Principal component analysis; Proportion of quality loss reduction; ...... On stochastic optimization: Taguchi MethodsTM demystified; its limitations and fallacy clarified.

  16. A modified principal component analysis-based utility theory ...

    African Journals Online (AJOL)

    traditional machining processes having multiple performance characteristics, some of which are usually correlated. So, ideally, use of principal component analysis (PCA)-based approaches that take into account the possible correlations ...

  17. Synthesis and spectroscopic analysis of Schiff Bases of Imesatin ...

    African Journals Online (AJOL)

    Synthesis and spectroscopic analysis of Schiff Bases of Imesatin and Isatin derivatives. Olubunmi S. Oguntoye, Abdulmumeen A. Hamid, Gabriel S. Iloka, Sunday O. Bodede, Samson O. Owalude, Adedibu C. Tella ...

  18. Risk-based decision analysis for groundwater operable units

    International Nuclear Information System (INIS)

    Chiaramonte, G.R.

    1995-01-01

    This document proposes a streamlined approach and methodology for performing risk assessment in support of interim remedial measure (IRM) decisions involving the remediation of contaminated groundwater on the Hanford Site. This methodology, referred to as ''risk-based decision analysis,'' also supports the specification of target cleanup volumes and provides a basis for design and operation of the groundwater remedies. The risk-based decision analysis can be completed within a short time frame and concisely documented. The risk-based decision analysis is more versatile than the qualitative risk assessment (QRA), because it not only supports the need for IRMs, but also provides criteria for defining the success of the IRMs and provides the risk-basis for decisions on final remedies. For these reasons, it is proposed that, for groundwater operable units, the risk-based decision analysis should replace the more elaborate, costly, and time-consuming QRA

  19. Adding trend data to Depletion-Based Stock Reduction Analysis

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — A Bayesian model of Depletion-Based Stock Reduction Analysis (DB-SRA), informed by a time series of abundance indexes, was developed, using the Sampling Importance...

  20. An Artificial Intelligence-Based Environment Quality Analysis System

    OpenAIRE

    Oprea , Mihaela; Iliadis , Lazaros

    2011-01-01

    Part 20: Informatics and Intelligent Systems Applications for Quality of Life information Services (ISQLIS) Workshop; International audience; The paper describes an environment quality analysis system based on a combination of some artificial intelligence techniques, artificial neural networks and rule-based expert systems. Two case studies of the system use are discussed: air pollution analysis and flood forecasting with their impact on the environment and on the population health. The syste...

  1. Content Analysis of a Computer-Based Faculty Activity Repository

    Science.gov (United States)

    Baker-Eveleth, Lori; Stone, Robert W.

    2013-01-01

    The research presents an analysis of faculty opinions regarding the introduction of a new computer-based faculty activity repository (FAR) in a university setting. The qualitative study employs content analysis to better understand the phenomenon underlying these faculty opinions and to augment the findings from a quantitative study. A web-based…

  2. PYTHON-based Physics Analysis Environment for LHCb

    CERN Document Server

    Belyaev, I; Mato, P; Barrand, G; Tsaregorodtsev, A; de Oliveira, E; Tsaregorodtsev, A Yu; De Oliveira, E

    2004-01-01

    BENDER is the PYTHON based physics analysis application for LHCb. It combines the best features of the underlying GAUDI software architecture with the flexibility of the PYTHON scripting language and provides end-users with a friendly physics analysis oriented environment.

  3. Product Lifecycle Management Architecture: A Model Based Systems Engineering Analysis.

    Energy Technology Data Exchange (ETDEWEB)

    Noonan, Nicholas James [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States)

    2015-07-01

    This report is an analysis of the Product Lifecycle Management (PLM) program. The analysis is centered on a need statement generated by a Nuclear Weapons (NW) customer. The need statement captured in this report creates an opportunity for the PLM to provide a robust service as a solution. Lifecycles for both the NW and PLM are analyzed using Model Based System Engineering (MBSE).

  4. Geographic Object-Based Image Analysis: Towards a new paradigm

    NARCIS (Netherlands)

    Blaschke, T.; Hay, G.J.; Kelly, M.; Lang, S.; Hofmann, P.; Addink, E.A.; Queiroz Feitosa, R.; van der Meer, F.D.; van der Werff, H.M.A.; van Coillie, F.; Tiede, A.

    2014-01-01

    The amount of scientific literature on (Geographic) Object-based Image Analysis – GEOBIA has been and still is sharply increasing. These approaches to analysing imagery have antecedents in earlier research on image segmentation and use GIS-like spatial analysis within classification and feature

  5. chemical analysis and base- promoted hydrolysis of locally ...

    African Journals Online (AJOL)

    Wara

    ABSTRACT. The study was on the chemical analysis and base- promoted hydrolysis of extracted shea nut fat. The local method of extraction of the shea nut oil was employed in comparison with literature report. A simple cold-process alkali hydrolysis of the shea nut oil was used in producing the soap. The chemical analysis ...

  6. Science Based Governance? EU Food Regulation Submitted to Risk Analysis

    NARCIS (Netherlands)

    Szajkowska, A.; Meulen, van der B.M.J.

    2014-01-01

    Anna Szajkowska and Bernd van der Meulen analyse in their contribution, Science Based Governance? EU Food Regulation Submitted to Risk Analysis, the scope of application of risk analysis and the precautionary principle in EU food safety regulation. To what extent does this technocratic,

  7. Phylogenetic Analysis of Tibetan Mastiffs Based on Mitochondrial ...

    Indian Academy of Sciences (India)

    Navya

    Phylogenetic analysis of Tibetan Mastiffs. RESEARCH ARTICLE. Phylogenetic Analysis of Tibetan Mastiffs Based on. Mitochondrial Hyper variable Region I. Zhanjun Ren*, Huiling Chen, Xuejiao Yang and Chengdong Zhang. College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi.

  8. Chemical analysis and base-promoted hydrolysis of locally ...

    African Journals Online (AJOL)

    The study was on the chemical analysis and base- promoted hydrolysis of extracted shea nut fat. The local method of extraction of the shea nut oil was employed in comparison with literature report. A simple cold-process alkali hydrolysis of the shea nut oil was used in producing the soap. The chemical analysis of the oil ...

  9. Some Linguistic-based and temporal analysis on Wikipedia

    International Nuclear Information System (INIS)

    Yasseri, T.

    2010-01-01

    Wikipedia as a web-based, collaborative, multilingual encyclopaedia project is a very suitable field to carry out research on social dynamics and to investigate the complex concepts of conflict, collaboration, competition, dispute, etc in a large community (∼26 Million) of Wikipedia users. The other face of Wikipedia as a productive society, is its output, consisting of (∼17) Millions of articles written unsupervised by unprofessional editors in more than 270 different languages. In this talk we report some analysis performed on Wikipedia in two different approaches: temporal analysis to characterize disputes and controversies among users and linguistic-based analysis to characterize linguistic features of English texts in Wikipedia. (author)

  10. Differential Regulatory Analysis Based on Coexpression Network in Cancer Research

    Directory of Open Access Journals (Sweden)

    Junyi Li

    2016-01-01

    Full Text Available With rapid development of high-throughput techniques and accumulation of big transcriptomic data, plenty of computational methods and algorithms such as differential analysis and network analysis have been proposed to explore genome-wide gene expression characteristics. These efforts are aiming to transform underlying genomic information into valuable knowledges in biological and medical research fields. Recently, tremendous integrative research methods are dedicated to interpret the development and progress of neoplastic diseases, whereas differential regulatory analysis (DRA based on gene coexpression network (GCN increasingly plays a robust complement to regular differential expression analysis in revealing regulatory functions of cancer related genes such as evading growth suppressors and resisting cell death. Differential regulatory analysis based on GCN is prospective and shows its essential role in discovering the system properties of carcinogenesis features. Here we briefly review the paradigm of differential regulatory analysis based on GCN. We also focus on the applications of differential regulatory analysis based on GCN in cancer research and point out that DRA is necessary and extraordinary to reveal underlying molecular mechanism in large-scale carcinogenesis studies.

  11. A scenario-based procedure for seismic risk analysis

    International Nuclear Information System (INIS)

    Kluegel, J.-U.; Mualchin, L.; Panza, G.F.

    2006-12-01

    A new methodology for seismic risk analysis based on probabilistic interpretation of deterministic or scenario-based hazard analysis, in full compliance with the likelihood principle and therefore meeting the requirements of modern risk analysis, has been developed. The proposed methodology can easily be adjusted to deliver its output in a format required for safety analysts and civil engineers. The scenario-based approach allows the incorporation of all available information collected in a geological, seismotectonic and geotechnical database of the site of interest as well as advanced physical modelling techniques to provide a reliable and robust deterministic design basis for civil infrastructures. The robustness of this approach is of special importance for critical infrastructures. At the same time a scenario-based seismic hazard analysis allows the development of the required input for probabilistic risk assessment (PRA) as required by safety analysts and insurance companies. The scenario-based approach removes the ambiguity in the results of probabilistic seismic hazard analysis (PSHA) which relies on the projections of Gutenberg-Richter (G-R) equation. The problems in the validity of G-R projections, because of incomplete to total absence of data for making the projections, are still unresolved. Consequently, the information from G-R must not be used in decisions for design of critical structures or critical elements in a structure. The scenario-based methodology is strictly based on observable facts and data and complemented by physical modelling techniques, which can be submitted to a formalised validation process. By means of sensitivity analysis, knowledge gaps related to lack of data can be dealt with easily, due to the limited amount of scenarios to be investigated. The proposed seismic risk analysis can be used with confidence for planning, insurance and engineering applications. (author)

  12. Static Analysis for Event-Based XML Processing

    DEFF Research Database (Denmark)

    Møller, Anders

    2008-01-01

    Event-based processing of XML data - as exemplified by the popular SAX framework - is a powerful alternative to using W3C's DOM or similar tree-based APIs. The event-based approach is a streaming fashion with minimal memory consumption. This paper discusses challenges for creating program analyses...... for SAX applications. In particular, we consider the problem of statically guaranteeing the a given SAX program always produces only well-formed and valid XML output. We propose an analysis technique based on ecisting anglyses of Servlets, string operations, and XML graphs....

  13. Bayesian-network-based safety risk analysis in construction projects

    International Nuclear Information System (INIS)

    Zhang, Limao; Wu, Xianguo; Skibniewski, Miroslaw J.; Zhong, Jingbing; Lu, Yujie

    2014-01-01

    This paper presents a systemic decision support approach for safety risk analysis under uncertainty in tunnel construction. Fuzzy Bayesian Networks (FBN) is used to investigate causal relationships between tunnel-induced damage and its influential variables based upon the risk/hazard mechanism analysis. Aiming to overcome limitations on the current probability estimation, an expert confidence indicator is proposed to ensure the reliability of the surveyed data for fuzzy probability assessment of basic risk factors. A detailed fuzzy-based inference procedure is developed, which has a capacity of implementing deductive reasoning, sensitivity analysis and abductive reasoning. The “3σ criterion” is adopted to calculate the characteristic values of a triangular fuzzy number in the probability fuzzification process, and the α-weighted valuation method is adopted for defuzzification. The construction safety analysis progress is extended to the entire life cycle of risk-prone events, including the pre-accident, during-construction continuous and post-accident control. A typical hazard concerning the tunnel leakage in the construction of Wuhan Yangtze Metro Tunnel in China is presented as a case study, in order to verify the applicability of the proposed approach. The results demonstrate the feasibility of the proposed approach and its application potential. A comparison of advantages and disadvantages between FBN and fuzzy fault tree analysis (FFTA) as risk analysis tools is also conducted. The proposed approach can be used to provide guidelines for safety analysis and management in construction projects, and thus increase the likelihood of a successful project in a complex environment. - Highlights: • A systemic Bayesian network based approach for safety risk analysis is developed. • An expert confidence indicator for probability fuzzification is proposed. • Safety risk analysis progress is extended to entire life cycle of risk-prone events. • A typical

  14. Crystallographically-based analysis of the NMR spectra of maghemite

    International Nuclear Information System (INIS)

    Spiers, K.M.; Cashion, J.D.

    2012-01-01

    All possible iron environments with respect to nearest neighbour vacancies in vacancy-ordered and vacancy-disordered maghemite have been evaluated and used as the foundation for a crystallographically-based analysis of the published NMR spectra of maghemite. The spectral components have been assigned to particular configurations and excellent agreement obtained in comparing predicted spectra with published spectra taken in applied magnetic fields. The broadness of the published NMR lines has been explained by calculations of the magnetic dipole fields at the various iron sites and consideration of the supertransferred hyperfine fields. - Highlights: ► Analysis of 57 Fe NMR of maghemite based on vacancy ordering and nearest neighbour vacancies. ► Assignment of NMR spectral components based on crystallographic analysis of unique iron sites. ► Strong agreement between predicted spectra and published spectra taken in applied magnetic fields. ► Maghemite NMR spectral broadening due to various iron sites and supertransferred hyperfine field.

  15. Matrix-based introduction to multivariate data analysis

    CERN Document Server

    Adachi, Kohei

    2016-01-01

    This book enables readers who may not be familiar with matrices to understand a variety of multivariate analysis procedures in matrix forms. Another feature of the book is that it emphasizes what model underlies a procedure and what objective function is optimized for fitting the model to data. The author believes that the matrix-based learning of such models and objective functions is the fastest way to comprehend multivariate data analysis. The text is arranged so that readers can intuitively capture the purposes for which multivariate analysis procedures are utilized: plain explanations of the purposes with numerical examples precede mathematical descriptions in almost every chapter. This volume is appropriate for undergraduate students who already have studied introductory statistics. Graduate students and researchers who are not familiar with matrix-intensive formulations of multivariate data analysis will also find the book useful, as it is based on modern matrix formulations with a special emphasis on ...

  16. European Climate - Energy Security Nexus. A model based scenario analysis

    International Nuclear Information System (INIS)

    Criqui, Patrick; Mima, Silvana

    2011-01-01

    In this research, we have provided an overview of the climate-security nexus in the European sector through a model based scenario analysis with POLES model. The analysis underline that under stringent climate policies, Europe take advantage of a double dividend in its capacity to develop a new cleaner energy model and in lower vulnerability to potential shocks on the international energy markets. (authors)

  17. European Climate - Energy Security Nexus. A model based scenario analysis

    Energy Technology Data Exchange (ETDEWEB)

    Criqui, Patrick; Mima, Silvana

    2011-01-15

    In this research, we have provided an overview of the climate-security nexus in the European sector through a model based scenario analysis with POLES model. The analysis underline that under stringent climate policies, Europe take advantage of a double dividend in its capacity to develop a new cleaner energy model and in lower vulnerability to potential shocks on the international energy markets. (authors)

  18. Managerial Methods Based on Analysis, Recommended to a Boarding House

    Directory of Open Access Journals (Sweden)

    Solomia Andreş

    2015-06-01

    Full Text Available The paper presents a few theoretical and practical contributions regarding the implementing of analysis based methods, respectively a SWOT and an economic analysis, from the perspective and the demands of a firm management which functions with profits due to the activity of a boarding house. The two types of managerial methods recommended to the firm offer real and complex information necessary for the knowledge of the firm status and the elaboration of prediction for the maintaining of business viability.

  19. Fast Template-based Shape Analysis using Diffeomorphic Iterative Centroid

    OpenAIRE

    Cury , Claire; Glaunès , Joan Alexis; Chupin , Marie; Colliot , Olivier

    2014-01-01

    International audience; A common approach for the analysis of anatomical variability relies on the estimation of a representative template of the population, followed by the study of this population based on the parameters of the deformations going from the template to the population. The Large Deformation Diffeomorphic Metric Mapping framework is widely used for shape analysis of anatomical structures, but computing a template with such framework is computationally expensive. In this paper w...

  20. Using the DOE Knowledge Base for Special Event Analysis

    Energy Technology Data Exchange (ETDEWEB)

    Armstrong, H.M.; Harris, J.M.; Young, C.J.

    1998-10-20

    The DOE Knowledge Base is a library of detailed information whose purpose is to support the United States National Data Center (USNDC) in its mission to monitor compliance with the Comprehensive Test Ban Treaty (CTBT). One of the important tasks which the USNDC must accomplish is to periodically perform detailed analysis of events of high interest, so-called "Special Events", to provide the national authority with information needed to make policy decisions. In this paper we investigate some possible uses of the Knowledge Base for Special Event Analysis (SEA), and make recommendations for improving Knowledge Base support for SEA. To analyze an event in detail, there are two basic types of data which must be used sensor-derived data (wave- forms, arrivals, events, etc.) and regiohalized contextual data (known sources, geological characteristics, etc.). Cur- rently there is no single package which can provide full access to both types of data, so for our study we use a separate package for each MatSeis, the Sandia Labs-developed MATLAB-based seismic analysis package, for wave- form data analysis, and ArcView, an ESRI product, for contextual data analysis. Both packages are well-suited to pro- totyping because they provide a rich set of currently available functionality and yet are also flexible and easily extensible, . Using these tools and Phase I Knowledge Base data sets, we show how the Knowledge Base can improve both the speed and the quality of SEA. Empirically-derived interpolated correction information can be accessed to improve both location estimates and associated error estimates. This information can in turn be used to identi~ any known nearby sources (e.g. mines, volcanos), which may then trigger specialized processing of the sensor data. Based on the location estimate, preferred magnitude formulas and discriminants can be retrieved, and any known blockages can be identified to prevent miscalculations. Relevant historic events can be identilled either by

  1. Digital Printing Quality Detection and Analysis Technology Based on CCD

    Science.gov (United States)

    He, Ming; Zheng, Liping

    2017-12-01

    With the help of CCD digital printing quality detection and analysis technology, it can carry out rapid evaluation and objective detection of printing quality, and can play a certain control effect on printing quality. It can be said CDD digital printing quality testing and analysis of the rational application of technology, its digital printing and printing materials for a variety of printing equipments to improve the quality of a very positive role. In this paper, we do an in-depth study and discussion based on the CCD digital print quality testing and analysis technology.

  2. Phosphoproteomics of the goat milk fat globule membrane: New insights into lipid droplet secretion from the mammary epithelial cell.

    Science.gov (United States)

    Henry, Céline; Saadaoui, Besma; Bouvier, Frédéric; Cebo, Christelle

    2015-07-01

    Mechanisms of milk lipid secretion are highly controversial. Analyzing the fine protein composition of the "milk fat globule membrane" (MFGM), the triple-layered membrane surrounding milk lipid droplets (LDs) can provide mechanistic clues to better understand LD biosynthesis and secretion pathways in mammary epithelial cells (MECs). We therefore combined a high-sensitive Q-Exactive LC-MS/MS analysis of MFGM-derived peptides to the use of an in-house database intended to improve protein identification in the goat species. Using this approach, we performed the identification of 442 functional groups of proteins in the MFGM from goat milk. To get a more dynamic view of intracellular mechanisms driving LD dynamics in the MECs, we decided to investigate for the first time whether MFGM proteins were phosphorylated. MFGM proteins were sequentially digested by lysine-C and trypsin proteases and the resulting peptides were fractionated by a strong cation exchange chromatography. Titanium beads were used to enrich phosphopeptides from strong cation exchange chromatography eluted fractions. This approach lets us pinpoint 271 sites of phosphorylation on 124 unique goat MFGM proteins. Enriched GO terms associated with phosphorylated MFGM proteins were protein transport and actin cytoskeleton organization. Gained data are discussed with regard to lipid secretory mechanisms in the MECs. All MS data have been deposited in the ProteomeXchange with identifier PXD001039 (http://proteomecentral.proteomexchange.org/dataset/PXD001039). © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  3. Nucleonica. Web-based software tools for simulation and analysis

    International Nuclear Information System (INIS)

    Magill, J.; Dreher, R.; Soti, Z.

    2014-01-01

    The authors present a description of the Nucleonica web-based portal for simulation and analysis for a wide range of commonly encountered nuclear science applications. Advantages of a web-based approach include availability wherever there is internet access, intuitive user-friendly interface, remote access to high-power computing resources, and continual maintenance, improvement, and addition of tools and techniques common to the nuclear science industry. A description of the nuclear data resources, and some applications is given.

  4. Reliability-Based Robustness Analysis for a Croatian Sports Hall

    DEFF Research Database (Denmark)

    Čizmar, Dean; Kirkegaard, Poul Henning; Sørensen, John Dalsgaard

    2011-01-01

    This paper presents a probabilistic approach for structural robustness assessment for a timber structure built a few years ago. The robustness analysis is based on a structural reliability based framework for robustness and a simplified mechanical system modelling of a timber truss system...... is expressed and evaluated by a robustness index. Next, the robustness is assessed using system reliability indices where the probabilistic failure model is modelled by a series system of parallel systems....

  5. Open access for ALICE analysis based on virtualization technology

    CERN Document Server

    Buncic, P; Schutz, Y

    2015-01-01

    Open access is one of the important leverages for long-term data preservation for a HEP experiment. To guarantee the usability of data analysis tools beyond the experiment lifetime it is crucial that third party users from the scientific community have access to the data and associated software. The ALICE Collaboration has developed a layer of lightweight components built on top of virtualization technology to hide the complexity and details of the experiment-specific software. Users can perform basic analysis tasks within CernVM, a lightweight generic virtual machine, paired with an ALICE specific contextualization. Once the virtual machine is launched, a graphical user interface is automatically started without any additional configuration. This interface allows downloading the base ALICE analysis software and running a set of ALICE analysis modules. Currently the available tools include fully documented tutorials for ALICE analysis, such as the measurement of strange particle production or the nuclear modi...

  6. Emergy Analysis and Sustainability Efficiency Analysis of Different Crop-Based Biodiesel in Life Cycle Perspective

    DEFF Research Database (Denmark)

    Ren, Jingzheng; Manzardo, Alessandro; Mazzi, Anna

    2013-01-01

    kinds of crop-based biodiesel including soybean-, rapeseed-, sunflower-, jatropha- and palm-based biodiesel production options are studied by emergy analysis; soybean-based scenario is recognized as the most sustainable scenario that should be chosen for further study in China. DEA method is used...... to evaluate the sustainability efficiencies of these options, and the biodiesel production systems based on soybean, sunflower, and palm are considered as DEA efficient, whereas rapeseed-based and jatropha-based scenarios are needed to be improved, and the improved methods have also been specified....

  7. Estimation of scientific publications’ structure in accounting and analysis based on the international data bases

    OpenAIRE

    Олійник, Оксана Вікторівна

    2016-01-01

    Total analysis of dynamics and structure of publications in accounting and analysis based on flows of foreign scientific publications in economics, presented in the subject classification of American Association of Economists, abstract magazine “Journal of Economic Literature” (JEL) and Social Science Research Network have been carried out.

  8. Web-based visual analysis for high-throughput genomics.

    Science.gov (United States)

    Goecks, Jeremy; Eberhard, Carl; Too, Tomithy; Nekrutenko, Anton; Taylor, James

    2013-06-13

    Visualization plays an essential role in genomics research by making it possible to observe correlations and trends in large datasets as well as communicate findings to others. Visual analysis, which combines visualization with analysis tools to enable seamless use of both approaches for scientific investigation, offers a powerful method for performing complex genomic analyses. However, there are numerous challenges that arise when creating rich, interactive Web-based visualizations/visual analysis applications for high-throughput genomics. These challenges include managing data flow from Web server to Web browser, integrating analysis tools and visualizations, and sharing visualizations with colleagues. We have created a platform simplifies the creation of Web-based visualization/visual analysis applications for high-throughput genomics. This platform provides components that make it simple to efficiently query very large datasets, draw common representations of genomic data, integrate with analysis tools, and share or publish fully interactive visualizations. Using this platform, we have created a Circos-style genome-wide viewer, a generic scatter plot for correlation analysis, an interactive phylogenetic tree, a scalable genome browser for next-generation sequencing data, and an application for systematically exploring tool parameter spaces to find good parameter values. All visualizations are interactive and fully customizable. The platform is integrated with the Galaxy (http://galaxyproject.org) genomics workbench, making it easy to integrate new visual applications into Galaxy. Visualization and visual analysis play an important role in high-throughput genomics experiments, and approaches are needed to make it easier to create applications for these activities. Our framework provides a foundation for creating Web-based visualizations and integrating them into Galaxy. Finally, the visualizations we have created using the framework are useful tools for high

  9. Nuclear power company activity based costing management analysis

    International Nuclear Information System (INIS)

    Xu Dan

    2012-01-01

    With Nuclear Energy Industry development, Nuclear Power Company has the continual promoting stress of inner management to the sustainable marketing operation development. In view of this, it is very imminence that Nuclear Power Company should promote the cost management levels and built the nuclear safety based lower cost competitive advantage. Activity based costing management (ABCM) transfer the cost management emphases from the 'product' to the 'activity' using the value chain analysis methods, cost driver analysis methods and so on. According to the analysis of the detail activities and the value chains, cancel the unnecessary activity, low down the resource consuming of the necessary activity, and manage the cost from the source, achieve the purpose of reducing cost, boosting efficiency and realizing the management value. It gets the conclusion from the detail analysis with the nuclear power company procedure and activity, and also with the selection to 'pieces analysis' of the important cost related project in the nuclear power company. The conclusion is that the activities of the nuclear power company has the obviously performance. It can use the management of ABC method. And with the management of the procedure and activity, it is helpful to realize the nuclear safety based low cost competitive advantage in the nuclear power company. (author)

  10. Modeling and Grid impedance Variation Analysis of Parallel Connected Grid Connected Inverter based on Impedance Based Harmonic Analysis

    DEFF Research Database (Denmark)

    Kwon, JunBum; Wang, Xiongfei; Bak, Claus Leth

    2014-01-01

    This paper addresses the harmonic compensation error problem existing with parallel connected inverter in the same grid interface conditions by means of impedance-based analysis and modeling. Unlike the single grid connected inverter, it is found that multiple parallel connected inverters and grid...... impedance can make influence to each other if they each have a harmonic compensation function. The analysis method proposed in this paper is based on the relationship between the overall output impedance and input impedance of parallel connected inverter, where controller gain design method, which can...

  11. Single base pair mutation analysis by PNA directed PCR clamping

    DEFF Research Database (Denmark)

    Ørum, H.; Nielsen, P.E.; Egholm, M.

    1993-01-01

    A novel method that allows direct analysis of single base mutation by the polymerase chain reaction (PCR) is described. The method utilizes the finding that PNAs (peptide nucleic acids) recognize and bind to their complementary nucleic acid sequences with higher thermal stability and specificity...

  12. Advancing School-Based Interventions through Economic Analysis

    Science.gov (United States)

    Olsson, Tina M.; Ferrer-Wreder, Laura; Eninger, Lilianne

    2014-01-01

    Commentators interested in school-based prevention programs point to the importance of economic issues for the future of prevention efforts. Many of the processes and aims of prevention science are dependent upon prevention resources. Although economic analysis is an essential tool for assessing resource use, the attention given economic analysis…

  13. Automated analysis of security requirements through risk-based argumentation

    NARCIS (Netherlands)

    Yu, Yijun; Nunes Leal Franqueira, V.; Tun, Thein Tan; Wieringa, Roelf J.; Nuseibeh, Bashar

    2015-01-01

    Computer-based systems are increasingly being exposed to evolving security threats, which often reveal new vulnerabilities. A formal analysis of the evolving threats is difficult due to a number of practical considerations such as incomplete knowledge about the design, limited information about

  14. Graph- versus Vector-Based Analysis of a Consensus Protocol

    NARCIS (Netherlands)

    Delzanno, Giorgio; Rensink, Arend; Traverso, Riccardo; Bošnački, Dragan; Edelkamp, Stefan; Lluch Lafuente, Alberto; Wijs, Anton

    The Paxos distributed consensus algorithm is a challenging case-study for standard, vector-based model checking techniques. Due to asynchronous communication, exhaustive analysis may generate very large state spaces already for small model instances. In this paper, we show the advantages of graph

  15. LES based POD analysis of Jet in Cross Flow

    DEFF Research Database (Denmark)

    Cavar, Dalibor; Meyer, Knud Erik; Jakirlic, S.

    2010-01-01

    The paper presents results of a POD investigation of the LES based numerical simulation of the jet-in-crossflow (JICF) flowfield. LES results are firstly compared to the pointwise LDA measurements. 2D POD analysis is then used as a comparison basis for PIV measurements and LES, and finally 3D POD...

  16. Computer-Based Interaction Analysis with DEGREE Revisited

    Science.gov (United States)

    Barros, B.; Verdejo, M. F.

    2016-01-01

    We review our research with "DEGREE" and analyse how our work has impacted the collaborative learning community since 2000. Our research is framed within the context of computer-based interaction analysis and the development of computer-supported collaborative learning (CSCL) tools. We identify some aspects of our work which have been…

  17. Intelligent assembly time analysis, using a digital knowledge based approach

    NARCIS (Netherlands)

    Jin, Y.; Curran, R.; Butterfield, J.; Burke, R.; Welch, B.

    2009-01-01

    The implementation of effective time analysis methods fast and accurately in the era of digital manufacturing has become a significant challenge for aerospace manufacturers hoping to build and maintain a competitive advantage. This paper proposes a structure oriented, knowledge-based approach for

  18. Potential density and tree survival: an analysis based on South ...

    African Journals Online (AJOL)

    Finally, we present a tree survival analysis, based on the Weibull distribution function, for the Nelshoogte replicated CCT study, which has been observed for almost 40 years after planting and provides information about tree survival in response to planting espacements ranging from 494 to 2 965 trees per hectare.

  19. Discrete Discriminant analysis based on tree-structured graphical models

    DEFF Research Database (Denmark)

    Perez de la Cruz, Gonzalo; Eslava, Guillermina

    The purpose of this paper is to illustrate the potential use of discriminant analysis based on tree{structured graphical models for discrete variables. This is done by comparing its empirical performance using estimated error rates for real and simulated data. The results show that discriminant...

  20. Synthesis and Spectroscopic Analysis of Schiff Bases of Imesatin ...

    African Journals Online (AJOL)

    ADOWIE PERE

    Keywords: Schiff bases, isatin, imesatin, spectroscopic analysis, biological activity. Isatin (1H-indole-2, 3-Dione) was first synthesized by. Erdman, 1840 and established by Laurent, 1841 as a product from the oxidation of indigo by nitric and chromic acids. The synthetic versatility of Isatin has led to the wide applications of ...

  1. Study and analysis of wavelet based image compression techniques ...

    African Journals Online (AJOL)

    This paper presented comprehensive study with performance analysis of very recent Wavelet transform based image compression techniques. Image compression is one of the necessities for such communication. The goals of image compression are to minimize the storage requirement and communication bandwidth.

  2. Spinoza II: Conceptual Case-Based Natural Language Analysis.

    Science.gov (United States)

    Schank, Roger C.; And Others

    This paper presents the theoretical changes that have developed in Conceptual Dependency Theory and their ramifications in computer analysis of natural language. The major items of concern are: the elimination of reliance on "grammar rules" for parsing with the emphasis given to conceptual rule based parsing; the development of a…

  3. Analysis of a Lorentz force based vibration exciter using permanent ...

    Indian Academy of Sciences (India)

    This work presents performance analysis of a Lorentz force based noncontact vibration exciter by mounting a couple of permanent magnets on a piezoelectric stack. A conductor is attached to the structure to be excited and is placed midway between unlike poles of a couple of permanent magnets. The permanent magnets ...

  4. Likelihood-Based Confidence Intervals in Exploratory Factor Analysis

    NARCIS (Netherlands)

    Oort, Frans J.

    2011-01-01

    In exploratory or unrestricted factor analysis, all factor loadings are free to be estimated. In oblique solutions, the correlations between common factors are free to be estimated as well. The purpose of this article is to show how likelihood-based confidence intervals can be obtained for rotated

  5. Likelihood-based confidence intervals in exploratory factor analysis

    NARCIS (Netherlands)

    Oort, F.J.

    2011-01-01

    In exploratory or unrestricted factor analysis, all factor loadings are free to be estimated. In oblique solutions, the correlations between common factors are free to be estimated as well. The purpose of this article is to show how likelihood-based confidence intervals can be obtained for rotated

  6. Likelihood-Based Confidence Intervals in Exploratory Factor Analysis

    Science.gov (United States)

    Oort, Frans J.

    2011-01-01

    In exploratory or unrestricted factor analysis, all factor loadings are free to be estimated. In oblique solutions, the correlations between common factors are free to be estimated as well. The purpose of this article is to show how likelihood-based confidence intervals can be obtained for rotated factor loadings and factor correlations, by…

  7. Knowledge-based analysis of functional impacts of mutations in ...

    Indian Academy of Sciences (India)

    2015-09-28

    Sep 28, 2015 ... pathway' and 'Epidermal growth factor receptor signaling pathway' were significantly and differentially enriched by the two sets of allele-specific target genes of miRNA hsa-miR-96. [Bhattacharya A and Cui Y 2015 Knowledge-based analysis of functional impacts of mutations in microRNA seed regions.

  8. Digital Simulation-Based Training: A Meta-Analysis

    Science.gov (United States)

    Gegenfurtner, Andreas; Quesada-Pallarès, Carla; Knogler, Maximilian

    2014-01-01

    This study examines how design characteristics in digital simulation-based learning environments moderate self-efficacy and transfer of learning. Drawing on social cognitive theory and the cognitive theory of multimedia learning, the meta-analysis psychometrically cumulated k?=?15 studies of 25 years of research with a total sample size of…

  9. Vision-based human motion analysis: An overview

    NARCIS (Netherlands)

    Poppe, Ronald Walter

    2007-01-01

    Markerless vision-based human motion analysis has the potential to provide an inexpensive, non-obtrusive solution for the estimation of body poses. The significant research effort in this domain has been motivated by the fact that many application areas, including surveillance, Human-Computer

  10. A Gradient Analysis-Based Study of Aeromagnetic Anomalies of ...

    African Journals Online (AJOL)

    An aeromagnetic intensity contour map of a part of Nupe Basin of Nigeria was acquired, digitized and analysed. This work was carried out for a better understanding of the study area using the Gradient analysis-based technique to calculate depth to basement and to interpret the aeromagnetic anomaly map of the area.

  11. Modal Analysis Based on the Random Decrement Technique

    DEFF Research Database (Denmark)

    Asmussen, J. C.; Brincker, Rune

    1998-01-01

    This article describes the work carried out within the project: Modal Analysis Based on the Random Decrement Technique - Application to Civil Engineering Structures. The project is part of the research programme: Dynamics of Structures sponsored by the Danish Technical Research Counsil. The planned...

  12. Analysis of Computer Network Information Based on "Big Data"

    Science.gov (United States)

    Li, Tianli

    2017-11-01

    With the development of the current era, computer network and large data gradually become part of the people's life, people use the computer to provide convenience for their own life, but at the same time there are many network information problems has to pay attention. This paper analyzes the information security of computer network based on "big data" analysis, and puts forward some solutions.

  13. System of gait analysis based on ground reaction force assessment

    Directory of Open Access Journals (Sweden)

    František Vaverka

    2015-12-01

    Full Text Available Background: Biomechanical analysis of gait employs various methods used in kinematic and kinetic analysis, EMG, and others. One of the most frequently used methods is kinetic analysis based on the assessment of the ground reaction forces (GRF recorded on two force plates. Objective: The aim of the study was to present a method of gait analysis based on the assessment of the GRF recorded during the stance phase of two steps. Methods: The GRF recorded with a force plate on one leg during stance phase has three components acting in directions: Fx - mediolateral, Fy - anteroposterior, and Fz - vertical. A custom-written MATLAB script was used for gait analysis in this study. This software displays instantaneous force data for both legs as Fx(t, Fy(t and Fz(t curves, automatically determines the extremes of functions and sets the visual markers defining the individual points of interest. Positions of these markers can be easily adjusted by the rater, which may be necessary if the GRF has an atypical pattern. The analysis is fully automated and analyzing one trial takes only 1-2 minutes. Results: The method allows quantification of temporal variables of the extremes of the Fx(t, Fy(t, Fz(t functions, durations of the braking and propulsive phase, duration of the double support phase, the magnitudes of reaction forces in extremes of measured functions, impulses of force, and indices of symmetry. The analysis results in a standardized set of 78 variables (temporal, force, indices of symmetry which can serve as a basis for further research and diagnostics. Conclusions: The resulting set of variable offers a wide choice for selecting a specific group of variables with consideration to a particular research topic. The advantage of this method is the standardization of the GRF analysis, low time requirements allowing rapid analysis of a large number of trials in a short time, and comparability of the variables obtained during different research measurements.

  14. Flow cytometry-based DNA hybridization and polymorphism analysis

    Energy Technology Data Exchange (ETDEWEB)

    Cai, H.; Kommander, K.; White, P.S.; Nolan, J.P.

    1998-07-01

    Functional analysis of the humane genome, including the quantification of differential gene expression and the identification of polymorphic sites and disease genes, is an important element of the Human Genome Project. Current methods of analysis are mainly gel-based assays that are not well-suited to rapid genome-scale analyses. To analyze DNA sequence on a large scale, robust and high throughput assays are needed. The authors are developing a suite of microsphere-based approaches employing fluorescence detection to screen and analyze genomic sequence. The approaches include competitive DNA hybridization to measure DNA or RNA targets in unknown samples, and oligo ligation or extension assays to analyze single-nucleotide polymorphisms. Apart from the advances of sensitivity, simplicity, and low sample consumption, these flow cytometric approaches have the potential for high throughput multiplexed analysis using multicolored microspheres and automated sample handling.

  15. Control volume based hydrocephalus research; analysis of human data

    Science.gov (United States)

    Cohen, Benjamin; Wei, Timothy; Voorhees, Abram; Madsen, Joseph; Anor, Tomer

    2010-11-01

    Hydrocephalus is a neuropathophysiological disorder primarily diagnosed by increased cerebrospinal fluid volume and pressure within the brain. To date, utilization of clinical measurements have been limited to understanding of the relative amplitude and timing of flow, volume and pressure waveforms; qualitative approaches without a clear framework for meaningful quantitative comparison. Pressure volume models and electric circuit analogs enforce volume conservation principles in terms of pressure. Control volume analysis, through the integral mass and momentum conservation equations, ensures that pressure and volume are accounted for using first principles fluid physics. This approach is able to directly incorporate the diverse measurements obtained by clinicians into a simple, direct and robust mechanics based framework. Clinical data obtained for analysis are discussed along with data processing techniques used to extract terms in the conservation equation. Control volume analysis provides a non-invasive, physics-based approach to extracting pressure information from magnetic resonance velocity data that cannot be measured directly by pressure instrumentation.

  16. Teaching-Learning Activity Modeling Based on Data Analysis

    Directory of Open Access Journals (Sweden)

    Kyungrog Kim

    2015-03-01

    Full Text Available Numerous studies are currently being carried out on personalized services based on data analysis to find and provide valuable information about information overload. Furthermore, the number of studies on data analysis of teaching-learning activities for personalized services in the field of teaching-learning is increasing, too. This paper proposes a learning style recency-frequency-durability (LS-RFD model for quantified analysis on the level of activities of learners, to provide the elements of teaching-learning activities according to the learning style of the learner among various parameters for personalized service. This is to measure preferences as to teaching-learning activity according to recency, frequency and durability of such activities. Based on the results, user characteristics can be classified into groups for teaching-learning activity by categorizing the level of preference and activity of the learner.

  17. Content-based analysis and indexing of sports video

    Science.gov (United States)

    Luo, Ming; Bai, Xuesheng; Xu, Guang-you

    2001-12-01

    An explosion of on-line image and video data in digital form is already well underway. With the exponential rise in interactive information exploration and dissemination through the World-Wide Web, the major inhibitors of rapid access to on-line video data are the management of capture and storage, and content-based intelligent search and indexing techniques. This paper proposes an approach for content-based analysis and event-based indexing of sports video. It includes a novel method to organize shots - classifying shots as close shots and far shots, an original idea of blur extent-based event detection, and an innovative local mutation-based algorithm for caption detection and retrieval. Results on extensive real TV programs demonstrate the applicability of our approach.

  18. Laser-Based Lighting: Experimental Analysis and Perspectives.

    Science.gov (United States)

    Trivellin, Nicola; Yushchenko, Maksym; Buffolo, Matteo; De Santi, Carlo; Meneghini, Matteo; Meneghesso, Gaudenzio; Zanoni, Enrico

    2017-10-11

    This paper presents an extensive analysis of the operating principles, theoretical background, advantages and limitations of laser-based lighting systems. In the first part of the paper we discuss the main advantages and issues of laser-based lighting, and present a comparison with conventional LED-lighting technology. In the second part of the paper, we present original experimental data on the stability and reliability of phosphor layers for laser lighting, based on high light-intensity and high-temperature degradation tests. In the third part of the paper (for the first time) we present a detailed comparison between three different solutions for laser lighting, based on (i) transmissive phosphor layers; (ii) a reflective/angled phosphor layer; and (iii) a parabolic reflector, by discussing the advantages and drawbacks of each approach. The results presented within this paper can be used as a guideline for the development of advanced lighting systems based on laser diodes.

  19. Laser-Based Lighting: Experimental Analysis and Perspectives

    Directory of Open Access Journals (Sweden)

    Nicola Trivellin

    2017-10-01

    Full Text Available This paper presents an extensive analysis of the operating principles, theoretical background, advantages and limitations of laser-based lighting systems. In the first part of the paper we discuss the main advantages and issues of laser-based lighting, and present a comparison with conventional LED-lighting technology. In the second part of the paper, we present original experimental data on the stability and reliability of phosphor layers for laser lighting, based on high light-intensity and high-temperature degradation tests. In the third part of the paper (for the first time we present a detailed comparison between three different solutions for laser lighting, based on (i transmissive phosphor layers; (ii a reflective/angled phosphor layer; and (iii a parabolic reflector, by discussing the advantages and drawbacks of each approach. The results presented within this paper can be used as a guideline for the development of advanced lighting systems based on laser diodes.

  20. Environmental Assessment: General Plan-Based Environmental Impact Analysis Process, Laughlin Air Force Base

    Science.gov (United States)

    2007-05-01

    BASED ENVIROMENTAL IMPACT ANALYSIS PROCESS LAUGHLIN AIR FORCE BASE, TEXAS AGENCY: 47th Flying Training Wing (FTW), Laughlin Air Force Base (AFB), Texas...in their decision-making process. The President’s Council on Environmental Quality (CEQ) has issued regulations to implement NEPA that include...Order (EO) 12898, Federal Actions to Address Environmental Justice in Minority Populations and Low-Income Populations, was issued by the President on

  1. Effects of Interventions Based in Behavior Analysis on Motor Skill Acquisition: A Meta-Analysis

    Science.gov (United States)

    Alstot, Andrew E.; Kang, Minsoo; Alstot, Crystal D.

    2013-01-01

    Techniques based in applied behavior analysis (ABA) have been shown to be useful across a variety of settings to improve numerous behaviors. Specifically within physical activity settings, several studies have examined the effect of interventions based in ABA on a variety of motor skills, but the overall effects of these interventions are unknown.…

  2. Intelligent data analysis based on rough correlativity matrix

    Science.gov (United States)

    Geng, Zhiqiang; Zhu, Qunxiong

    2003-09-01

    This paper proposes a new data analysis method based on rough sets by rough correlativity matrix. In rough set theory, a table called information system or database is used as a special kind of formal language to represent knowledge, a rough correlativity matrix (RCM) can be seen as an internal representation of equivalence relations. Furthermore, this paper provides a new heuristic attributes reduction algorithm based on matrix computing, such as using matrix correlative implements to replace the relations computing between sets. Finally the paper adopts information transition matrix (ITM) of information theory to represent the certainty or uncertainty decision rules based on probability theory, namely, the information matrix composed of certainty factors gives the degree of belief of decision rules, on the contrary the "invert" ITM composed of coverage factor gives the interpretation of decision rules. The result of instance analysis is shown that it is an efficient and feasible method to deal with decision information table.

  3. Geographical classification of Epimedium based on HPLC fingerprint analysis combined with multi-ingredients quantitative analysis.

    Science.gov (United States)

    Xu, Ning; Zhou, Guofu; Li, Xiaojuan; Lu, Heng; Meng, Fanyun; Zhai, Huaqiang

    2017-05-01

    A reliable and comprehensive method for identifying the origin and assessing the quality of Epimedium has been developed. The method is based on analysis of HPLC fingerprints, combined with similarity analysis, hierarchical cluster analysis (HCA), principal component analysis (PCA) and multi-ingredient quantitative analysis. Nineteen batches of Epimedium, collected from different areas in the western regions of China, were used to establish the fingerprints and 18 peaks were selected for the analysis. Similarity analysis, HCA and PCA all classified the 19 areas into three groups. Simultaneous quantification of the five major bioactive ingredients in the Epimedium samples was also carried out to confirm the consistency of the quality tests. These methods were successfully used to identify the geographical origin of the Epimedium samples and to evaluate their quality. Copyright © 2016 John Wiley & Sons, Ltd.

  4. Thermodynamics-based Metabolite Sensitivity Analysis in metabolic networks.

    Science.gov (United States)

    Kiparissides, A; Hatzimanikatis, V

    2017-01-01

    The increasing availability of large metabolomics datasets enhances the need for computational methodologies that can organize the data in a way that can lead to the inference of meaningful relationships. Knowledge of the metabolic state of a cell and how it responds to various stimuli and extracellular conditions can offer significant insight in the regulatory functions and how to manipulate them. Constraint based methods, such as Flux Balance Analysis (FBA) and Thermodynamics-based flux analysis (TFA), are commonly used to estimate the flow of metabolites through genome-wide metabolic networks, making it possible to identify the ranges of flux values that are consistent with the studied physiological and thermodynamic conditions. However, unless key intracellular fluxes and metabolite concentrations are known, constraint-based models lead to underdetermined problem formulations. This lack of information propagates as uncertainty in the estimation of fluxes and basic reaction properties such as the determination of reaction directionalities. Therefore, knowledge of which metabolites, if measured, would contribute the most to reducing this uncertainty can significantly improve our ability to define the internal state of the cell. In the present work we combine constraint based modeling, Design of Experiments (DoE) and Global Sensitivity Analysis (GSA) into the Thermodynamics-based Metabolite Sensitivity Analysis (TMSA) method. TMSA ranks metabolites comprising a metabolic network based on their ability to constrain the gamut of possible solutions to a limited, thermodynamically consistent set of internal states. TMSA is modular and can be applied to a single reaction, a metabolic pathway or an entire metabolic network. This is, to our knowledge, the first attempt to use metabolic modeling in order to provide a significance ranking of metabolites to guide experimental measurements. Copyright © 2016 International Metabolic Engineering Society. Published by Elsevier

  5. Kronecker Algebra-based Deadlock Analysis for Railway Systems

    Directory of Open Access Journals (Sweden)

    Robert Mittermayr

    2012-09-01

    Full Text Available Deadlock analysis for railway systems differs in several aspects from deadlock analysis in computer science. While the problem of deadlock analysis for standard computer systems is well-understood, multi-threaded embedded computer systems pose new challenges. A novel approach in this area can easily be applied to deadlock analysis in the domain of railway systems. The approach is based on Kronecker algebra. A lazy implementation of the matrix operations even allows analysing exponentially sized systems in a very efficient manner. The running time of the algorithm does not depend on the problem size but on the size of the solution. While other approaches suffer from the fact that additional constraints make the problem and its solution harder, our approach delivers its results faster if constraints are added. In addition, our approach is complete and sound for railway systems, i.e., it generates neither false positives nor false negatives.

  6. Incorporating Semantics into Data Driven Workflows for Content Based Analysis

    Science.gov (United States)

    Argüello, M.; Fernandez-Prieto, M. J.

    Finding meaningful associations between text elements and knowledge structures within clinical narratives in a highly verbal domain, such as psychiatry, is a challenging goal. The research presented here uses a small corpus of case histories and brings into play pre-existing knowledge, and therefore, complements other approaches that use large corpus (millions of words) and no pre-existing knowledge. The paper describes a variety of experiments for content-based analysis: Linguistic Analysis using NLP-oriented approaches, Sentiment Analysis, and Semantically Meaningful Analysis. Although it is not standard practice, the paper advocates providing automatic support to annotate the functionality as well as the data for each experiment by performing semantic annotation that uses OWL and OWL-S. Lessons learnt can be transmitted to legacy clinical databases facing the conversion of clinical narratives according to prominent Electronic Health Records standards.

  7. A computational network analysis based on targets of antipsychotic agents.

    Science.gov (United States)

    Gao, Lei; Feng, Shuo; Liu, Zhao-Yuan; Wang, Jiu-Qiang; Qi, Ke-Ke; Wang, Kai

    2018-03-01

    Currently, numerous antipsychotic agents have been developed in the area of pharmacological treatment of schizophrenia. However, the molecular mechanism underlying multi targets of antipsychotics were yet to be explored. In this study we performed a computational network analysis based on targets of antipsychotic agents. We retrieved a total of 96 targets from 56 antipsychotic agents. By expression enrichment analysis, we identified that the expressions of antipsychotic target genes were significantly enriched in liver, brain, blood and corpus striatum. By protein-protein interaction (PPI) network analysis, a PPI network with 77 significantly interconnected target genes was generated. By historeceptomics analysis, significant brain region specific target-drug interactions were identified in targets of dopamine receptors (DRD1-Olanzapine in caudate nucleus and pons (P-valueantipsychotic targets and insights for molecular mechanism of antipsychotic agents. Copyright © 2017 Elsevier B.V. All rights reserved.

  8. Phosphoproteomics identified Endofin, DCBLD2, and KIAA0582 as novel tyrosine phosphorylation targets of EGF signaling and Iressa in human cancer cells

    DEFF Research Database (Denmark)

    Chen, Yunhao; Low, Teck-Yew; Choong, Lee-Yee

    2007-01-01

    With the completion of the human genome project, analysis of enriched phosphotyrosyl proteins from epidermal growth factor (EGF)-induced phosphotyrosine proteome permits the identification of novel downstream substrates of the EGF receptor (EGFR). Using cICAT-based LC-MS/MS method, we identified...

  9. Applications of methacrylate-based monolithic supports for speciation analysis.

    Science.gov (United States)

    Scancar, Janez; Milacic, Radmila

    2009-08-01

    Liquid chromatography combined with element specific detection is commonly applied in speciation analysis. In these analyses, to obtain reliable data chemical species should not be transformed. To preserve chemical species during the separation step, fast chromatographic procedures and mild separation conditions are required. Monolithic supports that enable rapid chromatographic separations have rarely been used in speciation analysis. Methacrylate-based anion- and cation-exchange monolithic supports offer separation of charged chemical species of elements and can be used as a complementary tool to particle-packed liquid chromatographic columns. The present paper presents an overview of successful applications of methacrylate-based monolithic supports in speciation of zinc (Zn), chromium (Cr), and aluminium (Al) in environmental, occupational health, and biological samples. Measures of analytical performance of convective interaction media (CIM) monolithic chromatographic supports, namely selectivity, sensitivity, and time of analysis, are compared to those of particle-packed columns. The potential of CIM monolithic chromatography in speciation analysis is critically discussed. Direct comparison of the experimental data in speciation of elements by ion-exchange monolithic and fast protein liquid chromatography is reported for the first time. Finally, some recommendations are given for further investigations of the potential of monolithic chromatography and its implementations in different fields of element speciation analysis.

  10. Barcode server: a visualization-based genome analysis system.

    Directory of Open Access Journals (Sweden)

    Fenglou Mao

    Full Text Available We have previously developed a computational method for representing a genome as a barcode image, which makes various genomic features visually apparent. We have demonstrated that this visual capability has made some challenging genome analysis problems relatively easy to solve. We have applied this capability to a number of challenging problems, including (a identification of horizontally transferred genes, (b identification of genomic islands with special properties and (c binning of metagenomic sequences, and achieved highly encouraging results. These application results inspired us to develop this barcode-based genome analysis server for public service, which supports the following capabilities: (a calculation of the k-mer based barcode image for a provided DNA sequence; (b detection of sequence fragments in a given genome with distinct barcodes from those of the majority of the genome, (c clustering of provided DNA sequences into groups having similar barcodes; and (d homology-based search using Blast against a genome database for any selected genomic regions deemed to have interesting barcodes. The barcode server provides a job management capability, allowing processing of a large number of analysis jobs for barcode-based comparative genome analyses. The barcode server is accessible at http://csbl1.bmb.uga.edu/Barcode.

  11. Data analysis using a data base driven graphics animation system

    International Nuclear Information System (INIS)

    Schwieder, D.H.; Stewart, H.D.; Curtis, J.N.

    1985-01-01

    A graphics animation system has been developed at the Idaho National Engineering Laboratory (INEL) to assist engineers in the analysis of large amounts of time series data. Most prior attempts at computer animation of data involve the development of large and expensive problem-specific systems. This paper discusses a generalized interactive computer animation system designed to be used in a wide variety of data analysis applications. By using relational data base storage of graphics and control information, considerable flexibility in design and development of animated displays is achieved

  12. A microprocessor based picture analysis system for automatic track measurements

    International Nuclear Information System (INIS)

    Heinrich, W.; Trakowski, W.; Beer, J.; Schucht, R.

    1982-01-01

    In the last few years picture analysis became a powerful technique for measurements of nuclear tracks in plastic detectors. For this purpose rather expensive commercial systems are available. Two inexpensive microprocessor based systems with different resolution were developed. The video pictures of particles seen through a microscope are digitized in real time and the picture analysis is done by software. The microscopes are equipped with stages driven by stepping motors, which are controlled by separate microprocessors. A PDP 11/03 supervises the operation of all microprocessors and stores the measured data on its mass storage devices. (author)

  13. FARO base case post-test analysis by COMETA code

    Energy Technology Data Exchange (ETDEWEB)

    Annunziato, A.; Addabbo, C. [Joint Research Centre, Ispra (Italy)

    1995-09-01

    The paper analyzes the COMETA (Core Melt Thermal-Hydraulic Analysis) post test calculations of FARO Test L-11, the so-called Base Case Test. The FARO Facility, located at JRC Ispra, is used to simulate the consequences of Severe Accidents in Nuclear Power Plants under a variety of conditions. The COMETA Code has a 6 equations two phase flow field and a 3 phases corium field: the jet, the droplets and the fused-debris bed. The analysis shown that the code is able to pick-up all the major phenomena occurring during the fuel-coolant interaction pre-mixing phase.

  14. Model-based analysis and simulation of regenerative heat wheel

    DEFF Research Database (Denmark)

    Wu, Zhuang; Melnik, Roderick V. N.; Borup, F.

    2006-01-01

    of mathematical models for the thermal analysis of the fluid and wheel matrix. The effect of heat conduction in the direction of the fluid flow is taken into account and the influence of variations in rotating speed of the wheel as well as other characteristics (ambient temperature, airflow and geometric size......The rotary regenerator (also called the heat wheel) is an important component of energy intensive sectors, which is used in many heat recovery systems. In this paper, a model-based analysis of a rotary regenerator is carried out with a major emphasis given to the development and implementation...

  15. Fatigue Analysis of Automobile Control Arm Based on Ncode

    Directory of Open Access Journals (Sweden)

    Ren Huanmei

    2016-01-01

    Full Text Available In order to improve the vehicle chassis structure durability, the fatigue analysis and optimization design of the low control arm (LCA was taken. A finite element model was established. By using this model, the stress distribution and lowest point of lifetime of the control arm under fatigue load was calculated. Based on the results of analysis, the optimization scheme according to the structure characteristics of components was presented, and a solution to improve the control arm fatigue life was given out. The research provided reference for engineering application of calculation and optimization of chassis components fatigue life.

  16. Parametric Design and Mechanical Analysis of Beams based on SINOVATION

    Science.gov (United States)

    Xu, Z. G.; Shen, W. D.; Yang, D. Y.; Liu, W. M.

    2017-07-01

    In engineering practice, engineer needs to carry out complicated calculation when the loads on the beam are complex. The processes of analysis and calculation take a lot of time and the results are unreliable. So VS2005 and ADK are used to develop a software for beams design based on the 3D CAD software SINOVATION with C ++ programming language. The software can realize the mechanical analysis and parameterized design of various types of beams and output the report of design in HTML format. Efficiency and reliability of design of beams are improved.

  17. Model based process-product design and analysis

    DEFF Research Database (Denmark)

    Gani, Rafiqul

    This paper gives a perspective on modelling and the important role it has within product-process design and analysis. Different modelling issues related to development and application of systematic model-based solution approaches for product-process design is discussed and the need for a hybrid......, forms and complexity, together with their associated parameters. An example of a model-based system for design of chemicals based formulated products is also given....... model-based framework is highlighted. This framework should be able to manage knowledge-data, models, and associated methods and tools integrated with design work-flows and data-flows for specific product-process design problems. In particular, the framework needs to manage models of different types...

  18. Noodle based analytical devices for cost effective green chemical analysis.

    Science.gov (United States)

    Kiwfo, Kanokwan; Wongwilai, Wasin; Paengnakorn, Pathinan; Boonmapa, Sasithorn; Sateanchok, Suphasinee; Grudpan, Kate

    2018-05-01

    Noodle based analytical devices are proposed for cost effective green chemical analysis. Two noodle based analytical platforms have been examined. Conditions for flow with laminar behaviors could be established. Detection may be via a webcam camera or a flatbed scanner. Acid-base reactions were chosen as a model study. The assays of acetic acid and sodium hydroxide were investigated. Apart from bromothymol blue, simple aqueous extract of butterfly pea flower was used as a natural reagent. Another model was the assay of copper (Cu 2+ ) which was based on the redox reaction of copper (Cu 2+ ) with iodide to produce tri-iodide forming brown/black product with starch which already exists in the noodle platform. Demonstration to apply the noodle platforms for real samples was made. Copyright © 2017 Elsevier B.V. All rights reserved.

  19. YersiniaBase: a genomic resource and analysis platform for comparative analysis of Yersinia.

    Science.gov (United States)

    Tan, Shi Yang; Dutta, Avirup; Jakubovics, Nicholas S; Ang, Mia Yang; Siow, Cheuk Chuen; Mutha, Naresh Vr; Heydari, Hamed; Wee, Wei Yee; Wong, Guat Jah; Choo, Siew Woh

    2015-01-16

    Yersinia is a Gram-negative bacteria that includes serious pathogens such as the Yersinia pestis, which causes plague, Yersinia pseudotuberculosis, Yersinia enterocolitica. The remaining species are generally considered non-pathogenic to humans, although there is evidence that at least some of these species can cause occasional infections using distinct mechanisms from the more pathogenic species. With the advances in sequencing technologies, many genomes of Yersinia have been sequenced. However, there is currently no specialized platform to hold the rapidly-growing Yersinia genomic data and to provide analysis tools particularly for comparative analyses, which are required to provide improved insights into their biology, evolution and pathogenicity. To facilitate the ongoing and future research of Yersinia, especially those generally considered non-pathogenic species, a well-defined repository and analysis platform is needed to hold the Yersinia genomic data and analysis tools for the Yersinia research community. Hence, we have developed the YersiniaBase, a robust and user-friendly Yersinia resource and analysis platform for the analysis of Yersinia genomic data. YersiniaBase has a total of twelve species and 232 genome sequences, of which the majority are Yersinia pestis. In order to smooth the process of searching genomic data in a large database, we implemented an Asynchronous JavaScript and XML (AJAX)-based real-time searching system in YersiniaBase. Besides incorporating existing tools, which include JavaScript-based genome browser (JBrowse) and Basic Local Alignment Search Tool (BLAST), YersiniaBase also has in-house developed tools: (1) Pairwise Genome Comparison tool (PGC) for comparing two user-selected genomes; (2) Pathogenomics Profiling Tool (PathoProT) for comparative pathogenomics analysis of Yersinia genomes; (3) YersiniaTree for constructing phylogenetic tree of Yersinia. We ran analyses based on the tools and genomic data in YersiniaBase and the

  20. Dynamic Chest Image Analysis: Model-Based Perfusion Analysis in Dynamic Pulmonary Imaging

    Directory of Open Access Journals (Sweden)

    Kiuru Aaro

    2003-01-01

    Full Text Available The "Dynamic Chest Image Analysis" project aims to develop model-based computer analysis and visualization methods for showing focal and general abnormalities of lung ventilation and perfusion based on a sequence of digital chest fluoroscopy frames collected with the dynamic pulmonary imaging technique. We have proposed and evaluated a multiresolutional method with an explicit ventilation model for ventilation analysis. This paper presents a new model-based method for pulmonary perfusion analysis. According to perfusion properties, we first devise a novel mathematical function to form a perfusion model. A simple yet accurate approach is further introduced to extract cardiac systolic and diastolic phases from the heart, so that this cardiac information may be utilized to accelerate the perfusion analysis and improve its sensitivity in detecting pulmonary perfusion abnormalities. This makes perfusion analysis not only fast but also robust in computation; consequently, perfusion analysis becomes computationally feasible without using contrast media. Our clinical case studies with 52 patients show that this technique is effective for pulmonary embolism even without using contrast media, demonstrating consistent correlations with computed tomography (CT and nuclear medicine (NM studies. This fluoroscopical examination takes only about 2 seconds for perfusion study with only low radiation dose to patient, involving no preparation, no radioactive isotopes, and no contrast media.

  1. Heart Sound Biometric System Based on Marginal Spectrum Analysis

    Directory of Open Access Journals (Sweden)

    Fangqin Ren

    2013-02-01

    Full Text Available This work presents a heart sound biometric system based on marginal spectrum analysis, which is a new feature extraction technique for identification purposes. This heart sound identification system is comprised of signal acquisition, pre-processing, feature extraction, training, and identification. Experiments on the selection of the optimal values for the system parameters are conducted. The results indicate that the new spectrum coefficients result in a significant increase in the recognition rate of 94.40% compared with that of the traditional Fourier spectrum (84.32% based on a database of 280 heart sounds from 40 participants.

  2. Heart sound biometric system based on marginal spectrum analysis.

    Science.gov (United States)

    Zhao, Zhidong; Shen, Qinqin; Ren, Fangqin

    2013-02-18

    This work presents a heart sound biometric system based on marginal spectrum analysis, which is a new feature extraction technique for identification purposes. This heart sound identification system is comprised of signal acquisition, pre-processing, feature extraction, training, and identification. Experiments on the selection of the optimal values for the system parameters are conducted. The results indicate that the new spectrum coefficients result in a significant increase in the recognition rate of 94.40% compared with that of the traditional Fourier spectrum (84.32%) based on a database of 280 heart sounds from 40 participants. 

  3. Heart Sound Biometric System Based on Marginal Spectrum Analysis

    Science.gov (United States)

    Zhao, Zhidong; Shen, Qinqin; Ren, Fangqin

    2013-01-01

    This work presents a heart sound biometric system based on marginal spectrum analysis, which is a new feature extraction technique for identification purposes. This heart sound identification system is comprised of signal acquisition, pre-processing, feature extraction, training, and identification. Experiments on the selection of the optimal values for the system parameters are conducted. The results indicate that the new spectrum coefficients result in a significant increase in the recognition rate of 94.40% compared with that of the traditional Fourier spectrum (84.32%) based on a database of 280 heart sounds from 40 participants. PMID:23429515

  4. Transit Traffic Analysis Zone Delineating Method Based on Thiessen Polygon

    Directory of Open Access Journals (Sweden)

    Shuwei Wang

    2014-04-01

    Full Text Available A green transportation system composed of transit, busses and bicycles could be a significant in alleviating traffic congestion. However, the inaccuracy of current transit ridership forecasting methods is imposing a negative impact on the development of urban transit systems. Traffic Analysis Zone (TAZ delineating is a fundamental and essential step in ridership forecasting, existing delineating method in four-step models have some problems in reflecting the travel characteristics of urban transit. This paper aims to come up with a Transit Traffic Analysis Zone delineation method as supplement of traditional TAZs in transit service analysis. The deficiencies of current TAZ delineating methods were analyzed, and the requirements of Transit Traffic Analysis Zone (TTAZ were summarized. Considering these requirements, Thiessen Polygon was introduced into TTAZ delineating. In order to validate its feasibility, Beijing was then taken as an example to delineate TTAZs, followed by a spatial analysis of office buildings within a TTAZ and transit station departure passengers. Analysis result shows that the TTAZs based on Thiessen polygon could reflect the transit travel characteristic and is of in-depth research value.

  5. Open access for ALICE analysis based on virtualization technology

    International Nuclear Information System (INIS)

    Buncic, P; Gheata, M; Schutz, Y

    2015-01-01

    Open access is one of the important leverages for long-term data preservation for a HEP experiment. To guarantee the usability of data analysis tools beyond the experiment lifetime it is crucial that third party users from the scientific community have access to the data and associated software. The ALICE Collaboration has developed a layer of lightweight components built on top of virtualization technology to hide the complexity and details of the experiment-specific software. Users can perform basic analysis tasks within CernVM, a lightweight generic virtual machine, paired with an ALICE specific contextualization. Once the virtual machine is launched, a graphical user interface is automatically started without any additional configuration. This interface allows downloading the base ALICE analysis software and running a set of ALICE analysis modules. Currently the available tools include fully documented tutorials for ALICE analysis, such as the measurement of strange particle production or the nuclear modification factor in Pb-Pb collisions. The interface can be easily extended to include an arbitrary number of additional analysis modules. We present the current status of the tools used by ALICE through the CERN open access portal, and the plans for future extensions of this system. (paper)

  6. Open access for ALICE analysis based on virtualization technology

    Science.gov (United States)

    Buncic, P.; Gheata, M.; Schutz, Y.

    2015-12-01

    Open access is one of the important leverages for long-term data preservation for a HEP experiment. To guarantee the usability of data analysis tools beyond the experiment lifetime it is crucial that third party users from the scientific community have access to the data and associated software. The ALICE Collaboration has developed a layer of lightweight components built on top of virtualization technology to hide the complexity and details of the experiment-specific software. Users can perform basic analysis tasks within CernVM, a lightweight generic virtual machine, paired with an ALICE specific contextualization. Once the virtual machine is launched, a graphical user interface is automatically started without any additional configuration. This interface allows downloading the base ALICE analysis software and running a set of ALICE analysis modules. Currently the available tools include fully documented tutorials for ALICE analysis, such as the measurement of strange particle production or the nuclear modification factor in Pb-Pb collisions. The interface can be easily extended to include an arbitrary number of additional analysis modules. We present the current status of the tools used by ALICE through the CERN open access portal, and the plans for future extensions of this system.

  7. Job optimization in ATLAS TAG-based distributed analysis

    Science.gov (United States)

    Mambelli, M.; Cranshaw, J.; Gardner, R.; Maeno, T.; Malon, D.; Novak, M.

    2010-04-01

    The ATLAS experiment is projected to collect over one billion events/year during the first few years of operation. The efficient selection of events for various physics analyses across all appropriate samples presents a significant technical challenge. ATLAS computing infrastructure leverages the Grid to tackle the analysis across large samples by organizing data into a hierarchical structure and exploiting distributed computing to churn through the computations. This includes events at different stages of processing: RAW, ESD (Event Summary Data), AOD (Analysis Object Data), DPD (Derived Physics Data). Event Level Metadata Tags (TAGs) contain information about each event stored using multiple technologies accessible by POOL and various web services. This allows users to apply selection cuts on quantities of interest across the entire sample to compile a subset of events that are appropriate for their analysis. This paper describes new methods for organizing jobs using the TAGs criteria to analyze ATLAS data. It further compares different access patterns to the event data and explores ways to partition the workload for event selection and analysis. Here analysis is defined as a broader set of event processing tasks including event selection and reduction operations ("skimming", "slimming" and "thinning") as well as DPD making. Specifically it compares analysis with direct access to the events (AOD and ESD data) to access mediated by different TAG-based event selections. We then compare different ways of splitting the processing to maximize performance.

  8. HIV/AIDS counseling: analysis based on Paulo Freire.

    Science.gov (United States)

    Miranda, Karla Corrêa Lima; Barroso, Maria Grasiela Teixeira

    2007-01-01

    The study aimed to investigate the strategies health professionals use in HIV/AIDS counseling. This study is a qualitative research, based on Paulo Freire's theory and practice. Bardin's content analysis was used as the analysis technique. For the studied group, the counseling is focused on cognition, although new concepts permeating this subject are emerging. The main difficulties in counseling are related to the clients and the institution. The main facility is related to the team, which according to the group has a good relationship. Counseling represents a moment of distress, especially because it brings up existential questions to the counselor. It can be inferred that counseling is a special moment, but it does not constitute an educational moment yet. To obtain this goal, a counseling methodology is proposed, based on Paulo Freire's principles and concepts.

  9. Controller design based on μ analysis and PSO algorithm.

    Science.gov (United States)

    Lari, Ali; Khosravi, Alireza; Rajabi, Farshad

    2014-03-01

    In this paper an evolutionary algorithm is employed to address the controller design problem based on μ analysis. Conventional solutions to μ synthesis problem such as D-K iteration method often lead to high order, impractical controllers. In the proposed approach, a constrained optimization problem based on μ analysis is defined and then an evolutionary approach is employed to solve the optimization problem. The goal is to achieve a more practical controller with lower order. A benchmark system named two-tank system is considered to evaluate performance of the proposed approach. Simulation results show that the proposed controller performs more effective than high order H(∞) controller and has close responses to the high order D-K iteration controller as the common solution to μ synthesis problem. © 2013 ISA Published by ISA All rights reserved.

  10. Fusing Quantitative Requirements Analysis with Model-based Systems Engineering

    Science.gov (United States)

    Cornford, Steven L.; Feather, Martin S.; Heron, Vance A.; Jenkins, J. Steven

    2006-01-01

    A vision is presented for fusing quantitative requirements analysis with model-based systems engineering. This vision draws upon and combines emergent themes in the engineering milieu. "Requirements engineering" provides means to explicitly represent requirements (both functional and non-functional) as constraints and preferences on acceptable solutions, and emphasizes early-lifecycle review, analysis and verification of design and development plans. "Design by shopping" emphasizes revealing the space of options available from which to choose (without presuming that all selection criteria have previously been elicited), and provides means to make understandable the range of choices and their ramifications. "Model-based engineering" emphasizes the goal of utilizing a formal representation of all aspects of system design, from development through operations, and provides powerful tool suites that support the practical application of these principles. A first step prototype towards this vision is described, embodying the key capabilities. Illustrations, implications, further challenges and opportunities are outlined.

  11. Image-Analysis Based on Seed Phenomics in Sesame

    Directory of Open Access Journals (Sweden)

    Prasad R.

    2014-10-01

    Full Text Available The seed coat (testa structure of twenty-three cultivated (Sesamum indicum L. and six wild sesame (s. occidentale Regel & Heer., S. mulayanum Nair, S. prostratum Retz., S. radiatum Schumach. & Thonn., S. angustifolium (Oliv. Engl. and S. schinzianum Asch germplasm was analyzed from digital and Scanning Electron Microscopy (SEM images with dedicated software using the descriptors for computer based seed image analysis to understand the diversity of seed morphometric traits, which later on can be extended to screen and evaluate improved genotypes of sesame. Seeds of wild sesame species could conveniently be distinguished from cultivated varieties based on shape and architectural analysis. Results indicated discrete ‘cut off values to identify definite shape and contour of seed for a desirable sesame genotype along with the con-ventional practice of selecting lighter colored testa.

  12. Fuzzy-Set Based Sentiment Analysis of Big Social Data

    DEFF Research Database (Denmark)

    Mukkamala, Raghava Rao; Hussain, Abid; Vatrapu, Ravi

    2014-01-01

    Computational approaches to social media analytics are largely limited to graph theoretical approaches such as social network analysis (SNA) informed by the social philosophical approach of relational sociology. There are no other unified modelling approaches to social data that integrate...... the conceptual, formal, software, analytical and empirical realms. In this paper, we first present and discuss a theory and conceptual model of social data. Second, we outline a formal model based on fuzzy set theory and describe the operational semantics of the formal model with a real-world social data example...... from Facebook. Third, we briefly present and discuss the Social Data Analytics Tool (SODATO) that realizes the conceptual model in software and provisions social data analysis based on the conceptual and formal models. Fourth, we use SODATO to fetch social data from the facebook wall of a global brand...

  13. GNSS Spoofing Detection Based on Signal Power Measurements: Statistical Analysis

    Directory of Open Access Journals (Sweden)

    V. Dehghanian

    2012-01-01

    Full Text Available A threat to GNSS receivers is posed by a spoofing transmitter that emulates authentic signals but with randomized code phase and Doppler values over a small range. Such spoofing signals can result in large navigational solution errors that are passed onto the unsuspecting user with potentially dire consequences. An effective spoofing detection technique is developed in this paper, based on signal power measurements and that can be readily applied to present consumer grade GNSS receivers with minimal firmware changes. An extensive statistical analysis is carried out based on formulating a multihypothesis detection problem. Expressions are developed to devise a set of thresholds required for signal detection and identification. The detection processing methods developed are further manipulated to exploit incidental antenna motion arising from user interaction with a GNSS handheld receiver to further enhance the detection performance of the proposed algorithm. The statistical analysis supports the effectiveness of the proposed spoofing detection technique under various multipath conditions.

  14. AB019. Erectile dysfunction: analysis based on age stratification

    OpenAIRE

    Kai, Zhang

    2015-01-01

    Objective To establish the profile of erectile dysfunction in different age groups, and analysis the effect of sildenafil based on age stratification. Subjects and Methods From 2007 to 2008, a total of 4,507 men diagnosed with erectile dysfunction (ED) were enrolled from 46 centers in China; 4,039 of these patients were treated with sildenafil and asked to complete the Erectile Function domain of the International Index of Erectile Function, Erection Hardness Score, and Quality of Erection Qu...

  15. Semantic Indexing and Retrieval based on Formal Concept Analysis

    OpenAIRE

    Codocedo , Victor; Lykourentzou , Ioanna; Napoli , Amedeo

    2012-01-01

    Semantic indexing and retrieval has become an important research area, as the available amount of information on the Web is growing more and more. In this paper, we introduce an original approach to semantic indexing and retrieval based on Formal Concept Analysis. The concept lattice is used as a semantic index and we propose an original algorithm for traversing the lattice and answering user queries. This framework has been used and evaluated on song datasets.

  16. Research on Air Quality Evaluation based on Principal Component Analysis

    Science.gov (United States)

    Wang, Xing; Wang, Zilin; Guo, Min; Chen, Wei; Zhang, Huan

    2018-01-01

    Economic growth has led to environmental capacity decline and the deterioration of air quality. Air quality evaluation as a fundamental of environmental monitoring and air pollution control has become increasingly important. Based on the principal component analysis (PCA), this paper evaluates the air quality of a large city in Beijing-Tianjin-Hebei Area in recent 10 years and identifies influencing factors, in order to provide reference to air quality management and air pollution control.

  17. Experience based ageing analysis of NPP protection automation in Finland

    International Nuclear Information System (INIS)

    Simola, K.

    2000-01-01

    This paper describes three successive studies on ageing of protection automation of nuclear power plants. These studies were aimed at developing a methodology for an experience based ageing analysis, and applying it to identify the most critical components from ageing and safety points of view. The analyses resulted also to suggestions for improvement of data collection systems for the purpose of further ageing analyses. (author)

  18. Comparative analysis of some brushless motors based on catalog data

    Directory of Open Access Journals (Sweden)

    Anton Kalapish

    2005-10-01

    Full Text Available Brushless motors (polyphased AC induction, synchronous and brushless DC motors have no alternatives in modern electric drives. They possess highly efficient and very wide range of speeds. The objective of this paper is to represent some relation between the basic parameters and magnitudes of electrical machines. This allows to be made a comparative analysis and a choice of motor concerning each particular case based not only on catalogue data or price for sale.

  19. A LITERATURE SURVEY ON RECOMMENDATION SYSTEM BASED ON SENTIMENTAL ANALYSIS

    OpenAIRE

    Achin Jain; Vanita Jain; Nidhi Kapoor

    2016-01-01

    Recommender systems have grown to be a critical research subject after the emergence of the first paper on collaborative filtering in the Nineties. Despite the fact that educational studies on recommender systems, has extended extensively over the last 10 years, there are deficiencies in the complete literature evaluation and classification of that research. Because of this, we reviewed articles on recommender structures, and then classified those based on sentiment analysis. The articles are...

  20. Computer based approach to fatigue analysis and design

    International Nuclear Information System (INIS)

    Comstock, T.R.; Bernard, T.; Nieb, J.

    1979-01-01

    An approach is presented which uses a mini-computer based system for data acquisition, analysis and graphic displays relative to fatigue life estimation and design. Procedures are developed for identifying an eliminating damaging events due to overall duty cycle, forced vibration and structural dynamic characteristics. Two case histories, weld failures in heavy vehicles and low cycle fan blade failures, are discussed to illustrate the overall approach. (orig.) 891 RW/orig. 892 RKD [de

  1. Knowledge-based analysis of functional impacts of mutations in ...

    Indian Academy of Sciences (India)

    Knowledge-based analysis of functional impacts of mutations in microRNA seed regions. Supplementary figure 1. Summary of predicted miRNA targets from TargetScan and miRanda for all the SNPs in miRNA seeds. Percentages of miRNA targets found from only TargetScan, from only miRanda and from both TargetScan ...

  2. Fuzzy-Set Based Sentiment Analysis of Big Social Data

    DEFF Research Database (Denmark)

    Mukkamala, Raghava Rao; Hussain, Abid; Vatrapu, Ravi

    Computational approaches to social media analytics are largely limited to graph theoretical approaches such as social network analysis (SNA) informed by the social philosophical approach of relational sociology. There are no other unified modelling approaches to social data that integrate...... and actors on the facebook page. Sixth and last, we discuss the analytical method and conclude with a discussion of the benefits of set theoretical approaches based on the social philosophical approach of associational sociology....

  3. Diagnosis methods based on noise analysis at Cernavoda NPP, Romania

    International Nuclear Information System (INIS)

    Banica, Constantin; Dobrea, Dumitru

    1999-01-01

    This paper describes a recent noise analysis of the neutronic signals provided by in-core flux detectors (ICFD) and ion chambers (IC). This analysis is part of on-going program developed for Unit 1 of the Cernavoda NPP, Romania, with the following main objectives: - prediction of detector failures based on pattern recognition; - determination of fast excursions from steady states; - detection of abnormal mechanical vibrations in the reactor core. The introduction presents briefly the reactor, the location of ICFD's and IC's. The second section presents the data acquisition systems and their capabilities. The paper continues with a brief presentation of the numerical methods used for analysis (section 3). The most significant results can be found in section 4, while section 5 concludes about useful information that can be obtained from the neutronic signals at high power steady-state operation. (authors)

  4. [Model-based biofuels system analysis: a review].

    Science.gov (United States)

    Chang, Shiyan; Zhang, Xiliang; Zhao, Lili; Ou, Xunmin

    2011-03-01

    Model-based system analysis is an important tool for evaluating the potential and impacts of biofuels, and for drafting biofuels technology roadmaps and targets. The broad reach of the biofuels supply chain requires that biofuels system analyses span a range of disciplines, including agriculture/forestry, energy, economics, and the environment. Here we reviewed various models developed for or applied to modeling biofuels, and presented a critical analysis of Agriculture/Forestry System Models, Energy System Models, Integrated Assessment Models, Micro-level Cost, Energy and Emission Calculation Models, and Specific Macro-level Biofuel Models. We focused on the models' strengths, weaknesses, and applicability, facilitating the selection of a suitable type of model for specific issues. Such an analysis was a prerequisite for future biofuels system modeling, and represented a valuable resource for researchers and policy makers.

  5. Methodology for risk-based analysis of technical specifications

    International Nuclear Information System (INIS)

    Vesely, W.E.; Gaertner, J.P.; Wagner, D.P.

    1985-01-01

    Part of the effort by EPRI to apply probabilistic risk assessment methods and results to the solution of utility problems involves the investigation of methods for risk-based analysis of technical specifications. The culmination of this investigation is the SOCRATES computer code developed by Battelle's Columbus Laboratories to assist in the evaluation of technical specifications of nuclear power plants. The program is designed to use information found in PRAs to re-evaluate risk for changes in component allowed outage times (AOTs) and surveillance test intervals (STIs). The SOCRATES program is a unique and important tool for technical specification evaluations. The detailed component unavailability model allows a detailed analysis of AOT and STI contributions to risk. Explicit equations allow fast and inexpensive calculations. Because the code is designed to accept ranges of parameters and to save results of calculations that do not change during the analysis, sensitivity studies are efficiently performed and results are clearly displayed

  6. Facial Affect Recognition Using Regularized Discriminant Analysis-Based Algorithms

    Directory of Open Access Journals (Sweden)

    Cheng-Yuan Shih

    2010-01-01

    Full Text Available This paper presents a novel and effective method for facial expression recognition including happiness, disgust, fear, anger, sadness, surprise, and neutral state. The proposed method utilizes a regularized discriminant analysis-based boosting algorithm (RDAB with effective Gabor features to recognize the facial expressions. Entropy criterion is applied to select the effective Gabor feature which is a subset of informative and nonredundant Gabor features. The proposed RDAB algorithm uses RDA as a learner in the boosting algorithm. The RDA combines strengths of linear discriminant analysis (LDA and quadratic discriminant analysis (QDA. It solves the small sample size and ill-posed problems suffered from QDA and LDA through a regularization technique. Additionally, this study uses the particle swarm optimization (PSO algorithm to estimate optimal parameters in RDA. Experiment results demonstrate that our approach can accurately and robustly recognize facial expressions.

  7. Analysis Of Japans Economy Based On 2014 From Macroeconomics Prospects

    Directory of Open Access Journals (Sweden)

    Dr Mohammad Rafiqul Islam

    2015-02-01

    Full Text Available Abstract Japan is the worlds third largest economy. But currently economic situations of Japan are not stable. It is not increasing as expected. Since 2013 it was world second largest economy but Japan loosed its placed to China in 2014 due to slow growth of important economic indicators. By using the basic Keynesian model we will provide a detailed analysis of the short and long run impacts of the changes for Japans real GDP rate of unemployment and inflation rate. We demonstrated a detailed use of the 45-degree diagram or the AD-IA model and other economic analysis of the macroeconomic principles that underlie the model and concepts. Finally we will recommend the government with a change in fiscal policy what based on the analysis by considering what might be achieved with a fiscal policy response and the extent to which any impact on the stock of public debt might be a consideration

  8. SVM-based glioma grading. Optimization by feature reduction analysis

    International Nuclear Information System (INIS)

    Zoellner, Frank G.; Schad, Lothar R.; Emblem, Kyrre E.; Harvard Medical School, Boston, MA; Oslo Univ. Hospital

    2012-01-01

    We investigated the predictive power of feature reduction analysis approaches in support vector machine (SVM)-based classification of glioma grade. In 101 untreated glioma patients, three analytic approaches were evaluated to derive an optimal reduction in features; (i) Pearson's correlation coefficients (PCC), (ii) principal component analysis (PCA) and (iii) independent component analysis (ICA). Tumor grading was performed using a previously reported SVM approach including whole-tumor cerebral blood volume (CBV) histograms and patient age. Best classification accuracy was found using PCA at 85% (sensitivity = 89%, specificity = 84%) when reducing the feature vector from 101 (100-bins rCBV histogram + age) to 3 principal components. In comparison, classification accuracy by PCC was 82% (89%, 77%, 2 dimensions) and 79% by ICA (87%, 75%, 9 dimensions). For improved speed (up to 30%) and simplicity, feature reduction by all three methods provided similar classification accuracy to literature values (∝87%) while reducing the number of features by up to 98%. (orig.)

  9. Dynamic network-based epistasis analysis: Boolean examples

    Directory of Open Access Journals (Sweden)

    Eugenio eAzpeitia

    2011-12-01

    Full Text Available In this review we focus on how the hierarchical and single-path assumptions of epistasis analysis can bias the topologies of gene interactions infered. This has been acknowledged in several previous papers and reviews, but here we emphasize the critical importance of dynamic analyses, and specifically illustrate the use of Boolean network models. Epistasis in a broad sense refers to gene interactions, however, as originally proposed by Bateson (herein, classical epistasis, defined as the blocking of a particular allelic effect due to the effect of another allele at a different locus. Classical epistasis analysis has proven powerful and useful, allowing researchers to infer and assign directionality to gene interactions. As larger data sets are becoming available, the analysis of classical epistasis is being complemented with computer science tools and system biology approaches. We show that when the hierarchical and single-path assumptions are not met in classical epistasis analysis, the access to relevant information and the correct gene interaction topologies are hindered, and it becomes necessary to consider the temporal dynamics of gene interactions. The use of dynamical networks can overcome these limitations. We particularly focus on the use of Boolean networks that, like classical epistasis analysis, relies on logical formalisms, and hence can complement classical epistasis analysis and relax its assumptions. We develop a couple of theoretical examples and analyze them from a dynamic Boolean network model perspective. Boolean networks could help to guide additional experiments and discern among alternative regulatory schemes that would be impossible or difficult to infer without the elimination of these assumption from the classical epistasis analysis. We also use examples from the literature to show how a Boolean network-based approach has resolved ambiguities and guided epistasis analysis. Our review complements previous accounts, not

  10. Dynamic Network-Based Epistasis Analysis: Boolean Examples

    Science.gov (United States)

    Azpeitia, Eugenio; Benítez, Mariana; Padilla-Longoria, Pablo; Espinosa-Soto, Carlos; Alvarez-Buylla, Elena R.

    2011-01-01

    In this article we focus on how the hierarchical and single-path assumptions of epistasis analysis can bias the inference of gene regulatory networks. Here we emphasize the critical importance of dynamic analyses, and specifically illustrate the use of Boolean network models. Epistasis in a broad sense refers to gene interactions, however, as originally proposed by Bateson, epistasis is defined as the blocking of a particular allelic effect due to the effect of another allele at a different locus (herein, classical epistasis). Classical epistasis analysis has proven powerful and useful, allowing researchers to infer and assign directionality to gene interactions. As larger data sets are becoming available, the analysis of classical epistasis is being complemented with computer science tools and system biology approaches. We show that when the hierarchical and single-path assumptions are not met in classical epistasis analysis, the access to relevant information and the correct inference of gene interaction topologies is hindered, and it becomes necessary to consider the temporal dynamics of gene interactions. The use of dynamical networks can overcome these limitations. We particularly focus on the use of Boolean networks that, like classical epistasis analysis, relies on logical formalisms, and hence can complement classical epistasis analysis and relax its assumptions. We develop a couple of theoretical examples and analyze them from a dynamic Boolean network model perspective. Boolean networks could help to guide additional experiments and discern among alternative regulatory schemes that would be impossible or difficult to infer without the elimination of these assumption from the classical epistasis analysis. We also use examples from the literature to show how a Boolean network-based approach has resolved ambiguities and guided epistasis analysis. Our article complements previous accounts, not only by focusing on the implications of the hierarchical and

  11. Geographic Object-Based Image Analysis - Towards a new paradigm.

    Science.gov (United States)

    Blaschke, Thomas; Hay, Geoffrey J; Kelly, Maggi; Lang, Stefan; Hofmann, Peter; Addink, Elisabeth; Queiroz Feitosa, Raul; van der Meer, Freek; van der Werff, Harald; van Coillie, Frieke; Tiede, Dirk

    2014-01-01

    The amount of scientific literature on (Geographic) Object-based Image Analysis - GEOBIA has been and still is sharply increasing. These approaches to analysing imagery have antecedents in earlier research on image segmentation and use GIS-like spatial analysis within classification and feature extraction approaches. This article investigates these development and its implications and asks whether or not this is a new paradigm in remote sensing and Geographic Information Science (GIScience). We first discuss several limitations of prevailing per-pixel methods when applied to high resolution images. Then we explore the paradigm concept developed by Kuhn (1962) and discuss whether GEOBIA can be regarded as a paradigm according to this definition. We crystallize core concepts of GEOBIA, including the role of objects, of ontologies and the multiplicity of scales and we discuss how these conceptual developments support important methods in remote sensing such as change detection and accuracy assessment. The ramifications of the different theoretical foundations between the ' per-pixel paradigm ' and GEOBIA are analysed, as are some of the challenges along this path from pixels, to objects, to geo-intelligence. Based on several paradigm indications as defined by Kuhn and based on an analysis of peer-reviewed scientific literature we conclude that GEOBIA is a new and evolving paradigm.

  12. Improved nowcasting of precipitation based on convective analysis fields

    Directory of Open Access Journals (Sweden)

    T. Haiden

    2007-04-01

    Full Text Available The high-resolution analysis and nowcasting system INCA (Integrated Nowcasting through Comprehensive Analysis developed at the Austrian national weather service provides three-dimensional fields of temperature, humidity, and wind on an hourly basis, and two-dimensional fields of precipitation rate in 15 min intervals. The system operates on a horizontal resolution of 1 km and a vertical resolution of 100–200 m. It combines surface station data, remote sensing data (radar, satellite, forecast fields of the numerical weather prediction model ALADIN, and high-resolution topographic data. An important application of the INCA system is nowcasting of convective precipitation. Based on fine-scale temperature, humidity, and wind analyses a number of convective analysis fields are routinely generated. These fields include convective boundary layer (CBL flow convergence and specific humidity, lifted condensation level (LCL, convective available potential energy (CAPE, convective inhibition (CIN, and various convective stability indices. Based on the verification of areal precipitation nowcasts it is shown that the pure translational forecast of convective cells can be improved by using a decision algorithm which is based on a subset of the above fields, combined with satellite products.

  13. Management of Microbiologically Influenced Corrosion in Risk Based Inspection analysis

    DEFF Research Database (Denmark)

    Skovhus, Torben Lund; Hillier, Elizabeth; Andersen, Erlend S.

    2016-01-01

    Operating offshore oil and gas production facilities is often associated with high risk. In order to manage the risk, operators commonly use aids to support decision making in the establishment of a maintenance and inspection strategy. Risk Based Inspection (RBI) analysis is widely used in the of......Operating offshore oil and gas production facilities is often associated with high risk. In order to manage the risk, operators commonly use aids to support decision making in the establishment of a maintenance and inspection strategy. Risk Based Inspection (RBI) analysis is widely used...... in the offshore industry as a means to justify the inspection strategy adopted. The RBI analysis is a decision-making technique that enables asset managers to identify the risk related to failure of their most critical systems and components, with an effect on safety, environmental and business related issues...... and an extensive up-to date literature study. The parameters are discussed and subsequently combined in a novel procedure that allows assessment of MIC in a RBI analysis. The procedure is sub-divided into one screening step and a detailed assessment, which fits the recommended approach to assess risk in a RBI...

  14. Sensitivity analysis practices: Strategies for model-based inference

    Energy Technology Data Exchange (ETDEWEB)

    Saltelli, Andrea [Institute for the Protection and Security of the Citizen (IPSC), European Commission, Joint Research Centre, TP 361, 21020 Ispra (Vatican City State, Holy See,) (Italy)]. E-mail: andrea.saltelli@jrc.it; Ratto, Marco [Institute for the Protection and Security of the Citizen (IPSC), European Commission, Joint Research Centre, TP 361, 21020 Ispra (VA) (Italy); Tarantola, Stefano [Institute for the Protection and Security of the Citizen (IPSC), European Commission, Joint Research Centre, TP 361, 21020 Ispra (VA) (Italy); Campolongo, Francesca [Institute for the Protection and Security of the Citizen (IPSC), European Commission, Joint Research Centre, TP 361, 21020 Ispra (VA) (Italy)

    2006-10-15

    Fourteen years after Science's review of sensitivity analysis (SA) methods in 1989 (System analysis at molecular scale, by H. Rabitz) we search Science Online to identify and then review all recent articles having 'sensitivity analysis' as a keyword. In spite of the considerable developments which have taken place in this discipline, of the good practices which have emerged, and of existing guidelines for SA issued on both sides of the Atlantic, we could not find in our review other than very primitive SA tools, based on 'one-factor-at-a-time' (OAT) approaches. In the context of model corroboration or falsification, we demonstrate that this use of OAT methods is illicit and unjustified, unless the model under analysis is proved to be linear. We show that available good practices, such as variance based measures and others, are able to overcome OAT shortcomings and easy to implement. These methods also allow the concept of factors importance to be defined rigorously, thus making the factors importance ranking univocal. We analyse the requirements of SA in the context of modelling, and present best available practices on the basis of an elementary model. We also point the reader to available recipes for a rigorous SA.

  15. Sensitivity analysis practices: Strategies for model-based inference

    International Nuclear Information System (INIS)

    Saltelli, Andrea; Ratto, Marco; Tarantola, Stefano; Campolongo, Francesca

    2006-01-01

    Fourteen years after Science's review of sensitivity analysis (SA) methods in 1989 (System analysis at molecular scale, by H. Rabitz) we search Science Online to identify and then review all recent articles having 'sensitivity analysis' as a keyword. In spite of the considerable developments which have taken place in this discipline, of the good practices which have emerged, and of existing guidelines for SA issued on both sides of the Atlantic, we could not find in our review other than very primitive SA tools, based on 'one-factor-at-a-time' (OAT) approaches. In the context of model corroboration or falsification, we demonstrate that this use of OAT methods is illicit and unjustified, unless the model under analysis is proved to be linear. We show that available good practices, such as variance based measures and others, are able to overcome OAT shortcomings and easy to implement. These methods also allow the concept of factors importance to be defined rigorously, thus making the factors importance ranking univocal. We analyse the requirements of SA in the context of modelling, and present best available practices on the basis of an elementary model. We also point the reader to available recipes for a rigorous SA

  16. A Gene-Based Analysis of Acoustic Startle Latency

    Science.gov (United States)

    Smith, Alicia K.; Jovanovic, Tanja; Kilaru, Varun; Lori, Adriana; Gensler, Lauren; Lee, Samuel S.; Norrholm, Seth Davin; Massa, Nicholas; Cuthbert, Bruce; Bradley, Bekh; Ressler, Kerry J.; Duncan, Erica

    2017-01-01

    Latency of the acoustic startle response is the time required from the presentation of startling auditory stimulus until the startle response is elicited and provides an index of neural processing speed. Latency is prolonged in subjects with schizophrenia compared to controls in some but not all studies and is 68–90% heritable in baseline startle trials. In order to determine the genetic association with latency as a potential inroad into genetically based vulnerability to psychosis, we conducted a gene-based study of latency followed by an independent replication study of significant gene findings with a single-nucleotide polymorphism (SNP)-based analysis of schizophrenia and control subjects. 313 subjects from an urban population of low socioeconomic status with mixed psychiatric diagnoses were included in the gene-based study. Startle testing was conducted using a Biopac M150 system according to our published methods. Genotyping was performed with the Omni-Quad 1M or the Omni Express BeadChip. The replication study was conducted on 154 schizophrenia subjects and 123 psychiatric controls. Genetic analyses were conducted with Illumina Human Omni1-Quad and OmniExpress BeadChips. Twenty-nine SNPs were selected from four genes that were significant in the gene-based analysis and also associated with startle and/or schizophrenia in the literature. Linear regressions on latency were conducted, controlling for age, race, and diagnosis as a dichotomous variable. In the gene-based study, 2,870 genes demonstrated the evidence of association after correction for multiple comparisons (false discovery rate < 0.05). Pathway analysis of these genes revealed enrichment for relevant biological processes including neural transmission (p = 0.0029), synaptic transmission (p = 0.0032), and neuronal development (p = 0.024). The subsequent SNP-based replication analysis revealed a strong association of onset latency with the SNP rs901561 on the neuregulin gene (NRG1

  17. Ontology-based specification, identification and analysis of perioperative risks.

    Science.gov (United States)

    Uciteli, Alexandr; Neumann, Juliane; Tahar, Kais; Saleh, Kutaiba; Stucke, Stephan; Faulbrück-Röhr, Sebastian; Kaeding, André; Specht, Martin; Schmidt, Tobias; Neumuth, Thomas; Besting, Andreas; Stegemann, Dominik; Portheine, Frank; Herre, Heinrich

    2017-09-06

    Medical personnel in hospitals often works under great physical and mental strain. In medical decision-making, errors can never be completely ruled out. Several studies have shown that between 50 and 60% of adverse events could have been avoided through better organization, more attention or more effective security procedures. Critical situations especially arise during interdisciplinary collaboration and the use of complex medical technology, for example during surgical interventions and in perioperative settings (the period of time before, during and after surgical intervention). In this paper, we present an ontology and an ontology-based software system, which can identify risks across medical processes and supports the avoidance of errors in particular in the perioperative setting. We developed a practicable definition of the risk notion, which is easily understandable by the medical staff and is usable for the software tools. Based on this definition, we developed a Risk Identification Ontology (RIO) and used it for the specification and the identification of perioperative risks. An agent system was developed, which gathers risk-relevant data during the whole perioperative treatment process from various sources and provides it for risk identification and analysis in a centralized fashion. The results of such an analysis are provided to the medical personnel in form of context-sensitive hints and alerts. For the identification of the ontologically specified risks, we developed an ontology-based software module, called Ontology-based Risk Detector (OntoRiDe). About 20 risks relating to cochlear implantation (CI) have already been implemented. Comprehensive testing has indicated the correctness of the data acquisition, risk identification and analysis components, as well as the web-based visualization of results.

  18. Performance of Koyna dam based on static and dynamic analysis

    Science.gov (United States)

    Azizan, Nik Zainab Nik; Majid, Taksiah A.; Nazri, Fadzli Mohamed; Maity, Damodar

    2017-10-01

    This paper discusses the performance of Koyna dam based on static pushover analysis (SPO) and incremental dynamic analysis (IDA). The SPO in this study considered two type of lateral load which is inertial load and hydrodynamic load. The structure was analyse until the damage appears on the structure body. The IDA curves were develop based on 7 ground motion, where the characteristic of the ground motions: i) the distance from the epicenter is less than 15km, (ii) the magnitude is equal to or greater than 5.5 and (iii) the PGA is equal to or greater than 0.15g. All the ground motions convert to respond spectrum and scaled according to the developed elastic respond spectrum in order to match the characteristic of the ground motion to the soil type. Elastic respond spectrum developed based on soil type B by using Eurocode 8. By using SPO and IDA method are able to determine the limit states of the dam. The limit state proposed in this study are yielding and ultimate state which is identified base on crack pattern perform on the structure model. The comparison of maximum crest displacement for both methods is analysed to define the limit state of the dam. The displacement of yielding state for Koyna dam is 23.84mm and 44.91mm for the ultimate state. The results are able to be used as a guideline to monitor Koyna dam under seismic loadings which are considering static and dynamic.

  19. Analysis of Hylocereus spp. diversity based on phenetic method

    Science.gov (United States)

    Hamidah, Tsawab, Husnus; Rosmanida

    2017-06-01

    This study was aimed to determine number of distinguishing characters; the most dominant characters on dragonfruit (Hylocereus) classification; and dragonfruit classification relationship based on their morphological characters. Sampling was performed in Bhakti Alam Agrotourism, Pasuruan. Amount of observed parameters were 63 characters, including stem/branches segments, areolas, flower, fruit, and seeds characters. These characters were analyzed using descriptive and phenetic methods. Based on descriptive result, there were 59 distinguishing characters that affected classification of five dragonfruit species. They were white dragonfruit, pink dragonfruit, red dragonfruit, purplish-red dragonfruit, and yellow dragonfruit. Based on phenetic analysis, it was obtained a dendogram which showed the relationship of dragonfruit classification. Purplish-red and red dragonfruit were closely related with 50.7% in similarity value, which then these groups were referred as group VI. Pink dragonfruit and group VI were closely related with 43.3% in similarity value, which then these groups were referred as group IV. White dragonfruit and group IV were closely related with 21.5% in similarity value, which then these groups were referred to as group II. Meanwhile, yellow dragonfruit and group II were closely related with 8.5% in similarity value. Based on principal component analysis, there were 34 characters which influenced strongly dragonfruit classification. Two of them were the most dominant character that affected dragonfruit classification. They were curvature stem and number of fruit bracteola remnants, with component value 0,955.

  20. Web-Based Virtual Laboratory for Food Analysis Course

    Science.gov (United States)

    Handayani, M. N.; Khoerunnisa, I.; Sugiarti, Y.

    2018-02-01

    Implementation of learning on food analysis course in Program Study of Agro-industrial Technology Education faced problems. These problems include the availability of space and tools in the laboratory that is not comparable with the number of students also lack of interactive learning tools. On the other hand, the information technology literacy of students is quite high as well the internet network is quite easily accessible on campus. This is a challenge as well as opportunities in the development of learning media that can help optimize learning in the laboratory. This study aims to develop web-based virtual laboratory as one of the alternative learning media in food analysis course. This research is R & D (research and development) which refers to Borg & Gall model. The results showed that assessment’s expert of web-based virtual labs developed, in terms of software engineering aspects; visual communication; material relevance; usefulness and language used, is feasible as learning media. The results of the scaled test and wide-scale test show that students strongly agree with the development of web based virtual laboratory. The response of student to this virtual laboratory was positive. Suggestions from students provided further opportunities for improvement web based virtual laboratory and should be considered for further research.

  1. Climate policy decisions require policy-based lifecycle analysis.

    Science.gov (United States)

    Bento, Antonio M; Klotz, Richard

    2014-05-20

    Lifecycle analysis (LCA) metrics of greenhouse gas emissions are increasingly being used to select technologies supported by climate policy. However, LCAs typically evaluate the emissions associated with a technology or product, not the impacts of policies. Here, we show that policies supporting the same technology can lead to dramatically different emissions impacts per unit of technology added, due to multimarket responses to the policy. Using a policy-based consequential LCA, we find that the lifecycle emissions impacts of four US biofuel policies range from a reduction of 16.1 gCO2e to an increase of 24.0 gCO2e per MJ corn ethanol added by the policy. The differences between these results and representative technology-based LCA measures, which do not account for the policy instrument driving the expansion in the technology, illustrate the need for policy-based LCA measures when informing policy decision making.

  2. Graph- versus Vector-Based Analysis of a Consensus Protocol

    Directory of Open Access Journals (Sweden)

    Giorgio Delzanno

    2014-07-01

    Full Text Available The Paxos distributed consensus algorithm is a challenging case-study for standard, vector-based model checking techniques. Due to asynchronous communication, exhaustive analysis may generate very large state spaces already for small model instances. In this paper, we show the advantages of graph transformation as an alternative modelling technique. We model Paxos in a rich declarative transformation language, featuring (among other things nested quantifiers, and we validate our model using the GROOVE model checker, a graph-based tool that exploits isomorphism as a natural way to prune the state space via symmetry reductions. We compare the results with those obtained by the standard model checker Spin on the basis of a vector-based encoding of the algorithm.

  3. Economical analysis based on a simplified model of micro distillery

    International Nuclear Information System (INIS)

    Bristoti, A.; Adams, R.

    1987-01-01

    The investment costs of the hydrate alcohol distillery as well as the energy balance of its production made inviable its diffusion on a small scale. The present economical analysis is based on a simplified model of micro distillery where the reduction on investment costs in based on technical data based on the possibility of the utilization of an hydrate alcohol with a higher water constant than the usual, i. e. around 85 0 GL. The engineering project of this plant eliminates all pumps, all the liquids (water, sugar cane, syrup and wine) are fed by gravity. The bagasse is considered a noble by-product and it is utilized in poultry industry as a substitute of wood dust. All the heat needs of the micro distillery are supplied by wood. (author)

  4. Adaptive Human aware Navigation based on Motion Pattern Analysis

    DEFF Research Database (Denmark)

    Tranberg, Søren; Svenstrup, Mikael; Andersen, Hans Jørgen

    2009-01-01

    Respecting people’s social spaces is an important prerequisite for acceptable and natural robot navigation in human environments. In this paper, we describe an adaptive system for mobile robot navigation based on estimates of whether a person seeks to interact with the robot or not. The estimates...... are based on run-time motion pattern analysis compared to stored experience in a database. Using a potential field centered around the person, the robot positions itself at the most appropriate place relative to the person and the interaction status. The system is validated through qualitative tests...... in a real world setting. The results demonstrate that the system is able to learn to navigate based on past interaction experiences, and to adapt to different behaviors over time....

  5. Cost analysis of simulated base-catalyzed biodiesel production processes

    International Nuclear Information System (INIS)

    Tasić, Marija B.; Stamenković, Olivera S.; Veljković, Vlada B.

    2014-01-01

    Highlights: • Two semi-continuous biodiesel production processes from sunflower oil are simulated. • Simulations were based on the kinetics of base-catalyzed methanolysis reactions. • The total energy consumption was influenced by the kinetic model. • Heterogeneous base-catalyzed process is a preferable industrial technology. - Abstract: The simulation and economic feasibility evaluation of semi-continuous biodiesel production from sunflower oil were based on the kinetics of homogeneously (Process I) and heterogeneously (Process II) base-catalyzed methanolysis reactions. The annual plant’s capacity was determined to be 8356 tonnes of biodiesel. The total energy consumption was influenced by the unit model describing the methanolysis reaction kinetics. The energy consumption of the Process II was more than 2.5 times lower than that of the Process I. Also, the simulation showed the Process I had more and larger process equipment units, compared with the Process II. Based on lower total capital investment costs and biodiesel selling price, the Process II was economically more feasible than the Process I. Sensitivity analysis was conducted using variable sunflower oil and biodiesel prices. Using a biodiesel selling price of 0.990 $/kg, Processes I and II were shown to be economically profitable if the sunflower oil price was 0.525 $/kg and 0.696 $/kg, respectively

  6. Validation Database Based Thermal Analysis of an Advanced RPS Concept

    Science.gov (United States)

    Balint, Tibor S.; Emis, Nickolas D.

    2006-01-01

    Advanced RPS concepts can be conceived, designed and assessed using high-end computational analysis tools. These predictions may provide an initial insight into the potential performance of these models, but verification and validation are necessary and required steps to gain confidence in the numerical analysis results. This paper discusses the findings from a numerical validation exercise for a small advanced RPS concept, based on a thermal analysis methodology developed at JPL and on a validation database obtained from experiments performed at Oregon State University. Both the numerical and experimental configurations utilized a single GPHS module enabled design, resembling a Mod-RTG concept. The analysis focused on operating and environmental conditions during the storage phase only. This validation exercise helped to refine key thermal analysis and modeling parameters, such as heat transfer coefficients, and conductivity and radiation heat transfer values. Improved understanding of the Mod-RTG concept through validation of the thermal model allows for future improvements to this power system concept.

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

    DEFF Research Database (Denmark)

    2012-01-01

    Value Proposition The PhosProtect compound alone (developed and tested, IP secured)* • protects phospho-groups during tandem mass spectrometry, thus reducing problematic neutral loss of phosphate. • provides unique phospho-tag by causing isotopic distribution patterns in MS and MS/MS data. The Phos...

  8. Emergy Analysis and Sustainability Efficiency Analysis of Different Crop-Based Biodiesel in Life Cycle Perspective

    DEFF Research Database (Denmark)

    Ren, Jingzheng; Manzardo, Alessandro; Mazzi, Anna

    2013-01-01

    Biodiesel as a promising alternative energy resource has been a hot spot in chemical engineering nowadays, but there is also an argument about the sustainability of biodiesel. In order to analyze the sustainability of biodiesel production systems and select the most sustainable scenario, various...... kinds of crop-based biodiesel including soybean-, rapeseed-, sunflower-, jatropha- and palm-based biodiesel production options are studied by emergy analysis; soybean-based scenario is recognized as the most sustainable scenario that should be chosen for further study in China. DEA method is used...... to evaluate the sustainability efficiencies of these options, and the biodiesel production systems based on soybean, sunflower, and palm are considered as DEA efficient, whereas rapeseed-based and jatropha-based scenarios are needed to be improved, and the improved methods have also been specified....

  9. A linear mixture analysis-based compression for hyperspectral image analysis

    Energy Technology Data Exchange (ETDEWEB)

    C. I. Chang; I. W. Ginsberg

    2000-06-30

    In this paper, the authors present a fully constrained least squares linear spectral mixture analysis-based compression technique for hyperspectral image analysis, particularly, target detection and classification. Unlike most compression techniques that directly deal with image gray levels, the proposed compression approach generates the abundance fractional images of potential targets present in an image scene and then encodes these fractional images so as to achieve data compression. Since the vital information used for image analysis is generally preserved and retained in the abundance fractional images, the loss of information may have very little impact on image analysis. In some occasions, it even improves analysis performance. Airborne visible infrared imaging spectrometer (AVIRIS) data experiments demonstrate that it can effectively detect and classify targets while achieving very high compression ratios.

  10. Signal/noise analysis of FRET-based sensors.

    Science.gov (United States)

    Woehler, Andrew; Wlodarczyk, Jakub; Neher, Erwin

    2010-10-06

    Molecular sensors based on intramolecular Förster resonance energy transfer (FRET) have become versatile tools to monitor regulatory molecules in living tissue. However, their use is often compromised by low signal strength and excessive noise. We analyzed signal/noise (SNR) aspects of spectral FRET analysis methods, with the following conclusions: The most commonly used method (measurement of the emission ratio after a single short wavelength excitation) is optimal in terms of signal/noise, if only relative changes of this uncalibrated ratio are of interest. In the case that quantitative data on FRET efficiencies are required, these can be calculated from the emission ratio and some calibration parameters, but at reduced SNR. Lux-FRET, a recently described method for spectral analysis of FRET data, allows one to do so in three different ways, each based on a ratio of two out of three measured fluorescence signals (the donor and acceptor signal during a short-wavelength excitation and the acceptor signal during long wavelength excitation). Lux-FRET also allows for calculation of the total abundance of donor and acceptor fluorophores. The SNR for all these quantities is lower than that of the plain emission ratio due to unfavorable error propagation. However, if ligand concentration is calculated either from lux-FRET values or else, after its calibration, from the emission ratio, SNR for both analysis modes is very similar. Likewise, SNR values are similar, if the noise of these quantities is related to the expected dynamic range. We demonstrate these relationships based on data from an Epac-based cAMP sensor and discuss how the SNR changes with the FRET efficiency and the number of photons collected. Copyright © 2010 Biophysical Society. Published by Elsevier Inc. All rights reserved.

  11. The calcium-dependent protein kinase 3 of toxoplasma influences basal calcium levels and functions beyond egress as revealed by quantitative phosphoproteome analysis.

    Directory of Open Access Journals (Sweden)

    Moritz Treeck

    2014-06-01

    Full Text Available Calcium-dependent protein kinases (CDPKs are conserved in plants and apicomplexan parasites. In Toxoplasma gondii, TgCDPK3 regulates parasite egress from the host cell in the presence of a calcium-ionophore. The targets and the pathways that the kinase controls, however, are not known. To identify pathways regulated by TgCDPK3, we measured relative phosphorylation site usage in wild type and TgCDPK3 mutant and knock-out parasites by quantitative mass-spectrometry using stable isotope-labeling with amino acids in cell culture (SILAC. This revealed known and novel phosphorylation events on proteins predicted to play a role in host-cell egress, but also a novel function of TgCDPK3 as an upstream regulator of other calcium-dependent signaling pathways, as we also identified proteins that are differentially phosphorylated prior to egress, including proteins important for ion-homeostasis and metabolism. This observation is supported by the observation that basal calcium levels are increased in parasites where TgCDPK3 has been inactivated. Most of the differential phosphorylation observed in CDPK3 mutants is rescued by complementation of the mutants with a wild type copy of TgCDPK3. Lastly, the TgCDPK3 mutants showed hyperphosphorylation of two targets of a related calcium-dependent kinase (TgCDPK1, as well as TgCDPK1 itself, indicating that this latter kinase appears to play a role downstream of TgCDPK3 function. Overexpression of TgCDPK1 partially rescues the egress phenotype of the TgCDPK3 mutants, reinforcing this conclusion. These results show that TgCDPK3 plays a pivotal role in regulating tachyzoite functions including, but not limited to, egress.

  12. The Calcium-Dependent Protein Kinase 3 of Toxoplasma Influences Basal Calcium Levels and Functions beyond Egress as Revealed by Quantitative Phosphoproteome Analysis

    Science.gov (United States)

    Treeck, Moritz; Sanders, John L.; Gaji, Rajshekhar Y.; LaFavers, Kacie A.; Child, Matthew A.; Arrizabalaga, Gustavo; Elias, Joshua E.; Boothroyd, John C.

    2014-01-01

    Calcium-dependent protein kinases (CDPKs) are conserved in plants and apicomplexan parasites. In Toxoplasma gondii, TgCDPK3 regulates parasite egress from the host cell in the presence of a calcium-ionophore. The targets and the pathways that the kinase controls, however, are not known. To identify pathways regulated by TgCDPK3, we measured relative phosphorylation site usage in wild type and TgCDPK3 mutant and knock-out parasites by quantitative mass-spectrometry using stable isotope-labeling with amino acids in cell culture (SILAC). This revealed known and novel phosphorylation events on proteins predicted to play a role in host-cell egress, but also a novel function of TgCDPK3 as an upstream regulator of other calcium-dependent signaling pathways, as we also identified proteins that are differentially phosphorylated prior to egress, including proteins important for ion-homeostasis and metabolism. This observation is supported by the observation that basal calcium levels are increased in parasites where TgCDPK3 has been inactivated. Most of the differential phosphorylation observed in CDPK3 mutants is rescued by complementation of the mutants with a wild type copy of TgCDPK3. Lastly, the TgCDPK3 mutants showed hyperphosphorylation of two targets of a related calcium-dependent kinase (TgCDPK1), as well as TgCDPK1 itself, indicating that this latter kinase appears to play a role downstream of TgCDPK3 function. Overexpression of TgCDPK1 partially rescues the egress phenotype of the TgCDPK3 mutants, reinforcing this conclusion. These results show that TgCDPK3 plays a pivotal role in regulating tachyzoite functions including, but not limited to, egress. PMID:24945436

  13. Model-Based Evaluation Of System Scalability: Bandwidth Analysis For Smartphone-Based Biosensing Applications

    DEFF Research Database (Denmark)

    Patou, François; Madsen, Jan; Dimaki, Maria

    2016-01-01

    -engineering efforts for scaling a system specification efficaciously. We demonstrate the value of our methodology by investigating a smartphone-based biosensing instrumentation platform. Specifically, we carry out scalability analysis for the system’s bandwidth specification: the maximum analog voltage waveform...

  14. NeoAnalysis: a Python-based toolbox for quick electrophysiological data processing and analysis.

    Science.gov (United States)

    Zhang, Bo; Dai, Ji; Zhang, Tao

    2017-11-13

    In a typical electrophysiological experiment, especially one that includes studying animal behavior, the data collected normally contain spikes, local field potentials, behavioral responses and other associated data. In order to obtain informative results, the data must be analyzed simultaneously with the experimental settings. However, most open-source toolboxes currently available for data analysis were developed to handle only a portion of the data and did not take into account the sorting of experimental conditions. Additionally, these toolboxes require that the input data be in a specific format, which can be inconvenient to users. Therefore, the development of a highly integrated toolbox that can process multiple types of data regardless of input data format and perform basic analysis for general electrophysiological experiments is incredibly useful. Here, we report the development of a Python based open-source toolbox, referred to as NeoAnalysis, to be used for quick electrophysiological data processing and analysis. The toolbox can import data from different data acquisition systems regardless of their formats and automatically combine different types of data into a single file with a standardized format. In cases where additional spike sorting is needed, NeoAnalysis provides a module to perform efficient offline sorting with a user-friendly interface. Then, NeoAnalysis can perform regular analog signal processing, spike train, and local field potentials analysis, behavioral response (e.g. saccade) detection and extraction, with several options available for data plotting and statistics. Particularly, it can automatically generate sorted results without requiring users to manually sort data beforehand. In addition, NeoAnalysis can organize all of the relevant data into an informative table on a trial-by-trial basis for data visualization. Finally, NeoAnalysis supports analysis at the population level. With the multitude of general-purpose functions provided

  15. Cloud-Based Orchestration of a Model-Based Power and Data Analysis Toolchain

    Science.gov (United States)

    Post, Ethan; Cole, Bjorn; Dinkel, Kevin; Kim, Hongman; Lee, Erich; Nairouz, Bassem

    2016-01-01

    The proposed Europa Mission concept contains many engineering and scientific instruments that consume varying amounts of power and produce varying amounts of data throughout the mission. System-level power and data usage must be well understood and analyzed to verify design requirements. Numerous cross-disciplinary tools and analysis models are used to simulate the system-level spacecraft power and data behavior. This paper addresses the problem of orchestrating a consistent set of models, tools, and data in a unified analysis toolchain when ownership is distributed among numerous domain experts. An analysis and simulation environment was developed as a way to manage the complexity of the power and data analysis toolchain and to reduce the simulation turnaround time. A system model data repository is used as the trusted store of high-level inputs and results while other remote servers are used for archival of larger data sets and for analysis tool execution. Simulation data passes through numerous domain-specific analysis tools and end-to-end simulation execution is enabled through a web-based tool. The use of a cloud-based service facilitates coordination among distributed developers and enables scalable computation and storage needs, and ensures a consistent execution environment. Configuration management is emphasized to maintain traceability between current and historical simulation runs and their corresponding versions of models, tools and data.

  16. Complexity analysis based on generalized deviation for financial markets

    Science.gov (United States)

    Li, Chao; Shang, Pengjian

    2018-03-01

    In this paper, a new modified method is proposed as a measure to investigate the correlation between past price and future volatility for financial time series, known as the complexity analysis based on generalized deviation. In comparison with the former retarded volatility model, the new approach is both simple and computationally efficient. The method based on the generalized deviation function presents us an exhaustive way showing the quantization of the financial market rules. Robustness of this method is verified by numerical experiments with both artificial and financial time series. Results show that the generalized deviation complexity analysis method not only identifies the volatility of financial time series, but provides a comprehensive way distinguishing the different characteristics between stock indices and individual stocks. Exponential functions can be used to successfully fit the volatility curves and quantify the changes of complexity for stock market data. Then we study the influence for negative domain of deviation coefficient and differences during the volatile periods and calm periods. after the data analysis of the experimental model, we found that the generalized deviation model has definite advantages in exploring the relationship between the historical returns and future volatility.

  17. Resilience Analysis of Countries under Disasters Based on Multisource Data.

    Science.gov (United States)

    Zhang, Nan; Huang, Hong

    2018-01-01

    Disasters occur almost daily in the world. Because emergencies frequently have no precedent, are highly uncertain, and can be very destructive, improving a country's resilience is an efficient way to reduce risk. In this article, we collected more than 20,000 historical data points from disasters from 207 countries to enable us to calculate the severity of disasters and the danger they pose to countries. In addition, 6 primary indices (disaster, personal attribute, infrastructure, economics, education, and occupation) including 38 secondary influencing factors are considered in analyzing the resilience of countries. Using these data, we obtained the danger, expected number of deaths, and resilience of all 207 countries. We found that a country covering a large area is more likely to have a low resilience score. Through sensitivity analysis of all secondary indices, we found that population density, frequency of disasters, and GDP are the three most critical factors affecting resilience. Based on broad-spectrum resilience analysis of the different continents, Oceania and South America have the highest resilience, while Asia has the lowest. Over the past 50 years, the resilience of many countries has been improved sharply, especially in developing countries. Based on our results, we analyze the comprehensive resilience and provide some optimal suggestions to efficiently improve resilience. © 2017 Society for Risk Analysis.

  18. Techno-Economic Analysis of Biofuels Production Based on Gasification

    Energy Technology Data Exchange (ETDEWEB)

    Swanson, R. M.; Platon, A.; Satrio, J. A.; Brown, R. C.; Hsu, D. D.

    2010-11-01

    This study compares capital and production costs of two biomass-to-liquid production plants based on gasification. The first biorefinery scenario is an oxygen-fed, low-temperature (870?C), non-slagging, fluidized bed gasifier. The second scenario is an oxygen-fed, high-temperature (1,300?C), slagging, entrained flow gasifier. Both are followed by catalytic Fischer-Tropsch synthesis and hydroprocessing to naphtha-range (gasoline blend stock) and distillate-range (diesel blend stock) liquid fractions. Process modeling software (Aspen Plus) is utilized to organize the mass and energy streams and cost estimation software is used to generate equipment costs. Economic analysis is performed to estimate the capital investment and operating costs. Results show that the total capital investment required for nth plant scenarios is $610 million and $500 million for high-temperature and low-temperature scenarios, respectively. Product value (PV) for the high-temperature and low-temperature scenarios is estimated to be $4.30 and $4.80 per gallon of gasoline equivalent (GGE), respectively, based on a feedstock cost of $75 per dry short ton. Sensitivity analysis is also performed on process and economic parameters. This analysis shows that total capital investment and feedstock cost are among the most influential parameters affecting the PV.

  19. Medical diagnostics by laser-based analysis of exhaled breath

    Science.gov (United States)

    Giubileo, Gianfranco

    2002-08-01

    IMany trace gases can be found in the exhaled breath, some of them giving the possibility of a non invasive diagnosis of related diseases or allowing the monitoring of the disease in the course of its therapy. In the present lecture the principle of medical diagnosis based on the breath analysis will be introduced and the detection of trace gases in exhaled breath by high- resolution molecular spectroscopy in the IR spectral region will be discussed. A number of substrates and the optical systems for their laser detection will be reported. The following laser based experimental systems has been realised in the Molecular Spectroscopy Laboratory in ENEA in Frascati for the analysis of specific substances in the exhaled breath. A tuneable diode laser absorption spectroscopy (TDLAS) appartus for the measurement of 13C/12C isotopic ratio in carbon dioxide, a TDLAS apparatus for the detection of CH4 and a CO2 laser based photoacoustic system to detect trace ethylene at atmospheric pressure. The experimental set-up for each one of the a.m. optical systems will be shown and the related medical applications will be illustrated. The concluding remarks will be focuses on chemical species that are of major interest for medical people today and their diagnostic ability.

  20. Experimental Bifurcation Analysis Using Control-Based Continuation

    DEFF Research Database (Denmark)

    Bureau, Emil; Starke, Jens

    The focus of this thesis is developing and implementing techniques for performing experimental bifurcation analysis on nonlinear mechanical systems. The research centers around the newly developed control-based continuation method, which allows to systematically track branches of stable and unsta......The focus of this thesis is developing and implementing techniques for performing experimental bifurcation analysis on nonlinear mechanical systems. The research centers around the newly developed control-based continuation method, which allows to systematically track branches of stable...... procedure is applied to our test rig, resulting in a reliable non-invasive, locally stabilizing control. The use of stabilizing control makes it difficult to determine the stability of the underlying uncontrolled equilibrium. Based on the idea of momentarily modifying or disabling the control and study...... the resulting behavior, we propose and test three different methods for assessing stability of equilibrium states during experimental continuation. We show that it is possible to determine the stability without allowing unbounded divergence, and that it is under certain circumstances possible to quantify...

  1. [Detecting cardiac arrhythmias based on phase space analysis].

    Science.gov (United States)

    Sun, Rongrong; Wang, Yuanyuan; Yang, Su; Fang, Zuxiang

    2008-08-01

    It is important for cardiac therapy devices such as the automated external defibrillator to discriminate different cardiac disorders based on Electrocardiogram analysis. A phase space analysis based algorithm is proposed to detect cardiac arrhythmias effectively. Firstly, the phase space of the signal is reconstructed. Then from the viewpoint of geometry and information theory, the distribution entropy of the point density in the two-dimensional reconstructed phase space is calculated as the features in the further classification. Finally the nearest-neighbour method based on Mahalanobis distance is used to classify the sinus rhythm (SR), supraventricular tachyarrhythmia (SVTA), atrial flutter (AFL) and atrial fibrillation (AF). To evaluate the sensitivity, specificity and accuracy of this proposed method in the cardiac arrhythmias classification, the MIT-BIH arrhythmias database and the canine endocardial database are studied respectively. Experiment results demonstrate that the proposed method can detect SR, SVTA, AFL and AF signals rapidly and accurately with the simple computation. It promises to find application in automated devices for cardiac arrhythmias therapy.

  2. ALGORITHMS FOR TENNIS RACKET ANALYSIS BASED ON MOTION DATA

    Directory of Open Access Journals (Sweden)

    Maria Skublewska-Paszkowska

    2016-09-01

    Full Text Available Modern technologies, such as motion capture systems (both optical and markerless, are more and more frequently used for athlete performance analysis due to their great precision. Optical systems based on the retro-reflective markers allow for tracking motion of multiple objects of various types. These systems compute human kinetic and kinematic parameters based on biomechanical models. Tracking additional objects like a tennis racket is also a very important aspect for analysing the player’s technique and precision. The motion data gathered by motion capture systems may be used for analysing various aspects that may not be recognised by the human eye or a video camera. This paper presents algorithms for analysis of a tennis racket motion during two of the most important tennis strokes: forehand and backhand. An optical Vicon system was used for obtaining the motion data which was the input for the algorithms. They indicate: the velocity of a tennis racket’s head and the racket’s handle based on the trajectories of attached markers as well as the racket’s orientation. The algorithms were implemented and tested on the data obtained from a professional trainer who participated in the research and performed a series of ten strikes, separately for: 1 forehand without a ball, 2 backhand without a ball, 3 forehand with a ball and 4 backhand with a ball. The computed parameters are gathered in tables and visualised in a graph.

  3. Finite element analysis of osteoporosis models based on synchrotron radiation

    Science.gov (United States)

    Xu, W.; Xu, J.; Zhao, J.; Sun, J.

    2016-04-01

    With growing pressure of social aging, China has to face the increasing population of osteoporosis patients as well as the whole world. Recently synchrotron radiation has become an essential tool for biomedical exploration with advantage of high resolution and high stability. In order to study characteristic changes in different stages of primary osteoporosis, this research focused on the different periods of osteoporosis of rats based on synchrotron radiation. Both bone histomorphometry analysis and finite element analysis were then carried on according to the reconstructed three dimensional models. Finally, the changes of bone tissue in different periods were compared quantitatively. Histomorphometry analysis showed that the structure of the trabecular in osteoporosis degraded as the bone volume decreased. For femurs, the bone volume fraction (Bone volume/ Total volume, BV/TV) decreased from 69% to 43%. That led to the increase of the thickness of trabecular separation (from 45.05μ m to 97.09μ m) and the reduction of the number of trabecular (from 7.99 mm-1 to 5.97mm-1). Simulation of various mechanical tests with finite element analysis (FEA) indicated that, with the exacerbation of osteoporosis, the bones' ability of resistance to compression, bending and torsion gradually became weaker. The compression stiffness of femurs decreased from 1770.96 Fμ m-1 to 697.41 Fμ m-1, the bending and torsion stiffness were from 1390.80 Fμ m-1 to 566.11 Fμ m-1 and from 2957.28N.m/o to 691.31 N.m/o respectively, indicated the decrease of bone strength, and it matched the histomorphometry analysis. This study suggested that FEA and synchrotron radiation were excellent methods for analysing bone strength conbined with histomorphometry analysis.

  4. ICWorld: An MMOG-Based Approach to Analysis

    Directory of Open Access Journals (Sweden)

    Wyatt Wong

    2008-01-01

    Full Text Available Intelligence analysts routinely work with "wicked" problems—critical,time-sensitive problems where analytical errors can lead to catastrophic consequences for the nation's security. In the analyst's world, important decisions are often made quickly, and are made based on consuming, understanding, and piecing together enormous volumes of data. The data is not only voluminous, but often fragmented, subjective, inaccurate and fluid.Why does multi-player on-line gaming (MMOG technology matter to the IC? Fundamentally, there are two reasons. The first is technological: stripping away the gamelike content, MMOGs are dynamic systems that represent a physical world, where users are presented with (virtual life-and-death challenges that can only be overcome through planning, collaboration and communication. The second is cultural: the emerging generation of analysts is part of what is sometimes called the "Digital Natives" (Prensky 2001 and is fluent with interactive media. MMOGs enable faster visualization, data manipulation, collaboration and analysis than traditional text and imagery.ICWorld is an MMOG approach to intelligence analysis that fuses ideasfrom experts in the fields of gaming and data visualization, with knowledge of current and future intelligence analysis processes and tools. The concept has evolved over the last year as a result of evaluations by allsource analysts from around the IC. When fully developed, the Forterra team believes that ICWorld will fundamentally address major shortcomings of intelligence analysis, and dramatically improve the effectiveness of intelligence products.

  5. Beyond the GUM: variance-based sensitivity analysis in metrology

    International Nuclear Information System (INIS)

    Lira, I

    2016-01-01

    Variance-based sensitivity analysis is a well established tool for evaluating the contribution of the uncertainties in the inputs to the uncertainty in the output of a general mathematical model. While the literature on this subject is quite extensive, it has not found widespread use in metrological applications. In this article we present a succinct review of the fundamentals of sensitivity analysis, in a form that should be useful to most people familiarized with the Guide to the Expression of Uncertainty in Measurement (GUM). Through two examples, it is shown that in linear measurement models, no new knowledge is gained by using sensitivity analysis that is not already available after the terms in the so-called ‘law of propagation of uncertainties’ have been computed. However, if the model behaves non-linearly in the neighbourhood of the best estimates of the input quantities—and if these quantities are assumed to be statistically independent—sensitivity analysis is definitely advantageous for gaining insight into how they can be ranked according to their importance in establishing the uncertainty of the measurand. (paper)

  6. Psychoacoustic Music Analysis Based on the Discrete Wavelet Packet Transform

    Directory of Open Access Journals (Sweden)

    Xing He

    2008-01-01

    Full Text Available Psychoacoustical computational models are necessary for the perceptual processing of acoustic signals and have contributed significantly in the development of highly efficient audio analysis and coding. In this paper, we present an approach for the psychoacoustic analysis of musical signals based on the discrete wavelet packet transform. The proposed method mimics the multiresolution properties of the human ear closer than other techniques and it includes simultaneous and temporal auditory masking. Experimental results show that this method provides better masking capabilities and it reduces the signal-to-masking ratio substantially more than other approaches, without introducing audible distortion. This model can lead to greater audio compression by permitting further bit rate reduction and more secure watermarking by providing greater signal space for information hiding.

  7. Numerical analysis of a polysilicon-based resistive memory device

    KAUST Repository

    Berco, Dan

    2018-03-08

    This study investigates a conductive bridge resistive memory device based on a Cu top electrode, 10-nm polysilicon resistive switching layer and a TiN bottom electrode, by numerical analysis for $$10^{3}$$103 programming and erase simulation cycles. The low and high resistive state values in each cycle are calculated, and the analysis shows that the structure has excellent retention reliability properties. The presented Cu species density plot indicates that Cu insertion occurs almost exclusively along grain boundaries resulting in a confined isomorphic conductive filament that maintains its overall shape and electric properties during cycling. The superior reliability of this structure may thus be attributed to the relatively low amount of Cu migrating into the RSL during initial formation. In addition, the results show a good match and help to confirm experimental measurements done over a previously demonstrated device.

  8. GIS-based poverty and population distribution analysis in China

    Science.gov (United States)

    Cui, Jing; Wang, Yingjie; Yan, Hong

    2009-07-01

    Geographically, poverty status is not only related with social-economic factors but also strongly affected by geographical environment. In the paper, GIS-based poverty and population distribution analysis method is introduced for revealing their regional differences. More than 100000 poor villages and 592 national key poor counties are chosen for the analysis. The results show that poverty distribution tends to concentrate in most of west China and mountainous rural areas of mid China. Furthermore, the fifth census data are overlaid to those poor areas in order to gain its internal diversity of social-economic characteristics. By overlaying poverty related social-economic parameters, such as sex ratio, illiteracy, education level, percentage of ethnic minorities, family composition, finding shows that poverty distribution is strongly correlated with high illiteracy rate, high percentage minorities, and larger family member.

  9. Seismic Base Isolation Analysis for PASCAR Liquid Metal Reactor

    International Nuclear Information System (INIS)

    Lee, Kuk Hee; Yoo, Bong; Kim, Yun Jae

    2008-01-01

    This paper presents a study for developing a seismic isolation system for the PASCAR (Proliferation resistant, Accident-tolerant, Self-supported, Capsular and Assured Reactor) liquid metal reactor design. PASCAR use lead-bismuth eutectic (LBE) as coolant. Because the density (10,000kg/m 3 ) of LBE coolant is very heavier than sodium coolant and water, this presents a challenge to designers of the seismic isolation systems that will be used with these heavy liquid metal reactors. Finite element analysis is adapted to determine the characteristics of the isolator device. Results are presented from a study on the use of three-dimensional seismic isolation devices to the full-scale reactor. The seismic analysis responses of the two-dimensional and the three-dimensional isolation systems for the PASCAR are compared with that of the conventional fixed base system

  10. Real Time Engineering Analysis Based on a Generative Component Implementation

    DEFF Research Database (Denmark)

    Kirkegaard, Poul Henning; Klitgaard, Jens

    2007-01-01

    The present paper outlines the idea of a conceptual design tool with real time engineering analysis which can be used in the early conceptual design phase. The tool is based on a parametric approach using Generative Components with embedded structural analysis. Each of these components uses...... without jumping from aesthetics to structural digital design tools and back, but to work with both simultaneously and real time. The engineering level of knowledge is incorporated at a conceptual thinking level, i.e. qualitative information is used in stead of using quantitative information. An example...... with a static determinate roof structure modelled by beam components is given. The example outlines the idea of the tool for conceptual design in early phase of a multidisciplinary design process between architecture and structural engineering....

  11. Model-based human reliability analysis: prospects and requirements

    International Nuclear Information System (INIS)

    Mosleh, A.; Chang, Y.H.

    2004-01-01

    Major limitations of the conventional methods for human reliability analysis (HRA), particularly those developed for operator response analysis in probabilistic safety assessments (PSA) of nuclear power plants, are summarized as a motivation for the need and a basis for developing requirements for the next generation HRA methods. It is argued that a model-based approach that provides explicit cognitive causal links between operator behaviors and directly or indirectly measurable causal factors should be at the core of the advanced methods. An example of such causal model is briefly reviewed, where due to the model complexity and input requirements can only be currently implemented in a dynamic PSA environment. The computer simulation code developed for this purpose is also described briefly, together with current limitations in the models, data, and the computer implementation

  12. Automated migration analysis based on cell texture: method & reliability

    Directory of Open Access Journals (Sweden)

    Chittenden Thomas W

    2005-03-01

    Full Text Available Abstract Background In this paper, we present and validate a way to measure automatically the extent of cell migration based on automated examination of a series of digital photographs. It was designed specifically to identify the impact of Second Hand Smoke (SHS on endothelial cell migration but has broader applications. The analysis has two stages: (1 preprocessing of image texture, and (2 migration analysis. Results The output is a graphic overlay that indicates the front lines of cell migration superimposed on each original image, with automated reporting of the distance traversed vs. time. Expert preference compares to manual placement of leading edge shows complete equivalence of automated vs. manual leading edge definition for cell migration measurement. Conclusion Our method is indistinguishable from careful manual determinations of cell front lines, with the advantages of full automation, objectivity, and speed.

  13. Real Time Engineering Analysis Based on a Generative component Implementation

    DEFF Research Database (Denmark)

    Kirkegaard, Poul Henning; Klitgaard, Jens

    2007-01-01

    The present paper outlines the idea of a conceptual design tool with real time engineering analysis which can be used in the early conceptual design phase. The tool is based on a parametric approach using Generative Components with embedded structural analysis. Each of these components uses...... the geometry, material properties and fixed point characteristics to calculate the dimensions and subsequent feasibility of any architectural design. The proposed conceptual design tool provides the possibility for the architect to work with both the aesthetic as well as the structural aspects of architecture...... with a static determinate roof structure modelled by beam components is given. The example outlines the idea of the tool for conceptual design in early phase of a multidisciplinary design process between architecture and structural engineering....

  14. Ground extraction from airborne laser data based on wavelet analysis

    Science.gov (United States)

    Xu, Liang; Yang, Yan; Jiang, Bowen; Li, Jia

    2007-11-01

    With the advantages of high resolution and accuracy, airborne laser scanning data are widely used in topographic mapping. In order to generate a DTM, measurements from object features such as buildings, vehicles and vegetation have to be classified and removed. However, the automatic extraction of bare earth from point clouds acquired by airborne laser scanning equipment remains a problem in LIDAR data filtering nowadays. In this paper, a filter algorithm based on wavelet analysis is proposed. Relying on the capability of detecting discontinuities of continuous wavelet transform and the feature of multi-resolution analysis, the object points can be removed, while ground data are preserved. In order to evaluate the performance of this approach, we applied it to the data set used in the ISPRS filter test in 2003. 15 samples have been tested by the proposed approach. Results showed that it filtered most of the objects like vegetation and buildings, and extracted a well defined ground model.

  15. Analysis of reactor power oscillation based on nonlinear dynamic theory

    International Nuclear Information System (INIS)

    Suzudo, Tomoaki

    1994-07-01

    Reactor power oscillations are discussed based on nonlinear dynamic theory with reference to stability problem of boiling water reactors (BWRs). The reactor noise from an actual plant is, firstly, analyzed by a method originally used for the analysis of chaotic phenomenon. The results show that this method gives better dynamic descriptor of oscillatory motion than those from previous methods, and that it is applicable to real-time monitoring system of the reactor core. Next, the low-dimensional phenomenological model of BWR power oscillation is analytically studied using bifurcation theory, a branch of nonlinear dynamic theory. From this analysis are derived explicit expressions for the steady state's linear stability and weak stability not given by numerical analyses, and the qualitative properties of the power oscillation can be better understood. (author)

  16. Missile placement analysis based on improved SURF feature matching algorithm

    Science.gov (United States)

    Yang, Kaida; Zhao, Wenjie; Li, Dejun; Gong, Xiran; Sheng, Qian

    2015-03-01

    The precious battle damage assessment by use of video images to analysis missile placement is a new study area. The article proposed an improved speeded up robust features algorithm named restricted speeded up robust features, which combined the combat application of TV-command-guided missiles and the characteristics of video image. Its restrictions mainly reflected in two aspects, one is to restrict extraction area of feature point; the second is to restrict the number of feature points. The process of missile placement analysis based on video image was designed and a video splicing process and random sample consensus purification were achieved. The RSURF algorithm is proved that has good realtime performance on the basis of guarantee the accuracy.

  17. Histogram analysis for smartphone-based rapid hematocrit determination

    Science.gov (United States)

    Jalal, Uddin M.; Kim, Sang C.; Shim, Joon S.

    2017-01-01

    A novel and rapid analysis technique using histogram has been proposed for the colorimetric quantification of blood hematocrits. A smartphone-based “Histogram” app for the detection of hematocrits has been developed integrating the smartphone embedded camera with a microfluidic chip via a custom-made optical platform. The developed histogram analysis shows its effectiveness in the automatic detection of sample channel including auto-calibration and can analyze the single-channel as well as multi-channel images. Furthermore, the analyzing method is advantageous to the quantification of blood-hematocrit both in the equal and varying optical conditions. The rapid determination of blood hematocrits carries enormous information regarding physiological disorders, and the use of such reproducible, cost-effective, and standard techniques may effectively help with the diagnosis and prevention of a number of human diseases. PMID:28717569

  18. Cloud-based Jupyter Notebooks for Water Data Analysis

    Science.gov (United States)

    Castronova, A. M.; Brazil, L.; Seul, M.

    2017-12-01

    The development and adoption of technologies by the water science community to improve our ability to openly collaborate and share workflows will have a transformative impact on how we address the challenges associated with collaborative and reproducible scientific research. Jupyter notebooks offer one solution by providing an open-source platform for creating metadata-rich toolchains for modeling and data analysis applications. Adoption of this technology within the water sciences, coupled with publicly available datasets from agencies such as USGS, NASA, and EPA enables researchers to easily prototype and execute data intensive toolchains. Moreover, implementing this software stack in a cloud-based environment extends its native functionality to provide researchers a mechanism to build and execute toolchains that are too large or computationally demanding for typical desktop computers. Additionally, this cloud-based solution enables scientists to disseminate data processing routines alongside journal publications in an effort to support reproducibility. For example, these data collection and analysis toolchains can be shared, archived, and published using the HydroShare platform or downloaded and executed locally to reproduce scientific analysis. This work presents the design and implementation of a cloud-based Jupyter environment and its application for collecting, aggregating, and munging various datasets in a transparent, sharable, and self-documented manner. The goals of this work are to establish a free and open source platform for domain scientists to (1) conduct data intensive and computationally intensive collaborative research, (2) utilize high performance libraries, models, and routines within a pre-configured cloud environment, and (3) enable dissemination of research products. This presentation will discuss recent efforts towards achieving these goals, and describe the architectural design of the notebook server in an effort to support collaborative

  19. IMMAN: free software for information theory-based chemometric analysis.

    Science.gov (United States)

    Urias, Ricardo W Pino; Barigye, Stephen J; Marrero-Ponce, Yovani; García-Jacas, César R; Valdes-Martiní, José R; Perez-Gimenez, Facundo

    2015-05-01

    The features and theoretical background of a new and free computational program for chemometric analysis denominated IMMAN (acronym for Information theory-based CheMoMetrics ANalysis) are presented. This is multi-platform software developed in the Java programming language, designed with a remarkably user-friendly graphical interface for the computation of a collection of information-theoretic functions adapted for rank-based unsupervised and supervised feature selection tasks. A total of 20 feature selection parameters are presented, with the unsupervised and supervised frameworks represented by 10 approaches in each case. Several information-theoretic parameters traditionally used as molecular descriptors (MDs) are adapted for use as unsupervised rank-based feature selection methods. On the other hand, a generalization scheme for the previously defined differential Shannon's entropy is discussed, as well as the introduction of Jeffreys information measure for supervised feature selection. Moreover, well-known information-theoretic feature selection parameters, such as information gain, gain ratio, and symmetrical uncertainty are incorporated to the IMMAN software ( http://mobiosd-hub.com/imman-soft/ ), following an equal-interval discretization approach. IMMAN offers data pre-processing functionalities, such as missing values processing, dataset partitioning, and browsing. Moreover, single parameter or ensemble (multi-criteria) ranking options are provided. Consequently, this software is suitable for tasks like dimensionality reduction, feature ranking, as well as comparative diversity analysis of data matrices. Simple examples of applications performed with this program are presented. A comparative study between IMMAN and WEKA feature selection tools using the Arcene dataset was performed, demonstrating similar behavior. In addition, it is revealed that the use of IMMAN unsupervised feature selection methods improves the performance of both IMMAN and WEKA

  20. Analysis of manufacturing based on object oriented discrete event simulation

    Directory of Open Access Journals (Sweden)

    Eirik Borgen

    1990-01-01

    Full Text Available This paper describes SIMMEK, a computer-based tool for performing analysis of manufacturing systems, developed at the Production Engineering Laboratory, NTH-SINTEF. Its main use will be in analysis of job shop type of manufacturing. But certain facilities make it suitable for FMS as well as a production line manufacturing. This type of simulation is very useful in analysis of any types of changes that occur in a manufacturing system. These changes may be investments in new machines or equipment, a change in layout, a change in product mix, use of late shifts, etc. The effects these changes have on for instance the throughput, the amount of VIP, the costs or the net profit, can be analysed. And this can be done before the changes are made, and without disturbing the real system. Simulation takes into consideration, unlike other tools for analysis of manufacturing systems, uncertainty in arrival rates, process and operation times, and machine availability. It also shows the interaction effects a job which is late in one machine, has on the remaining machines in its route through the layout. It is these effects that cause every production plan not to be fulfilled completely. SIMMEK is based on discrete event simulation, and the modeling environment is object oriented. The object oriented models are transformed by an object linker into data structures executable by the simulation kernel. The processes of the entity objects, i.e. the products, are broken down to events and put into an event list. The user friendly graphical modeling environment makes it possible for end users to build models in a quick and reliable way, using terms from manufacturing. Various tests and a check of model logic are helpful functions when testing validity of the models. Integration with software packages, with business graphics and statistical functions, is convenient in the result presentation phase.

  1. Chest wall Ewing sarcoma: a population-based analysis.

    Science.gov (United States)

    Jacobs, Andrew J; Fishbein, Joanna; Levy, Carolyn Fein; Glick, Richard D

    2016-08-01

    The globally low incidence of pediatric chest wall Ewing sarcoma (CWES) has limited prior studies of this disease to mostly small, single-institution reviews. Our objective was to assess incidence, demographics, treatment patterns, and long-term survival of this disease through a population-based analysis. The Surveillance, Epidemiology, and End Results database was used to identify patients aged 0-21 y diagnosed with CWES from 1973 to 2011. Patients were grouped by decade to assess changes in treatment patterns and outcomes. The effects of clinical, demographic, and treatment variables on overall survival (OS) were assessed by the computation of Kaplan-Meier curves and the log-rank test, with Cox proportional hazard regression used for multivariable analysis. A total of 193 pediatric patients with histologically confirmed CWES were identified. The disease was more common in men (61%), whites (92%), and 11- to 17-y olds (49%). It was metastatic at presentation in 37% of patients. When grouped approximately by decade, 10-y OS improved progressively from 38% in 1973-1979 to 65% in 2000-2011 (P = 0.033). The use of radiation decreased from 84% in the earliest period to 40% in the most recent, whereas the proportion of patients receiving surgery increased from 75% to 85%. When controlling for covariates in multivariable analysis, male patients were found to have a higher mortality than female patients (hazard ratio: 2.4; confidence interval: 1.4, 4.4; P = 0.0028). This population-based analysis of CWES demonstrated an impressive trend of improving OS, with increasing use of surgery and decreasing use of radiation therapy. Our study demonstrated a gender difference in survival of CWES, with females having a better prognosis. The presence of metastatic disease is a very important prognostic factor for this illness. Copyright © 2016 Elsevier Inc. All rights reserved.

  2. Regional Analysis of Remote Sensing Based Evapotranspiration Information

    Science.gov (United States)

    Geli, H. M. E.; Hain, C.; Anderson, M. C.; Senay, G. B.

    2017-12-01

    Recent research findings on modeling actual evapotranspiration (ET) using remote sensing data and methods have proven the ability of these methods to address wide range of hydrological and water resources issues including river basin water balance for improved water resources management, drought monitoring, drought impact and socioeconomic responses, agricultural water management, optimization of land-use for water conservations, water allocation agreement among others. However, there is still a critical need to identify appropriate type of ET information that can address each of these issues. The current trend of increasing demand for water due to population growth coupled with variable and limited water supply due to drought especially in arid and semiarid regions with limited water supply have highlighted the need for such information. To properly address these issues different spatial and temporal resolutions of ET information will need to be used. For example, agricultural water management applications require ET information at field (30-m) and daily time scales while for river basin hydrologic analysis relatively coarser spatial and temporal scales can be adequate for such regional applications. The objective of this analysis is to evaluate the potential of using an integrated ET information that can be used to address some of these issues collectively. This analysis will highlight efforts to address some of the issues that are applicable to New Mexico including assessment of statewide water budget as well as drought impact and socioeconomic responses which all require ET information but at different spatial and temporal scales. This analysis will provide an evaluation of four remote sensing based ET models including ALEXI, DisALEXI, SSEBop, and SEBAL3.0. The models will be compared with ground-based observations from eddy covariance towers and water balance calculations. Remote sensing data from Landsat, MODIS, and VIIRS sensors will be used to provide ET

  3. Descriptor Based Analysis of Digital 3D Shapes

    DEFF Research Database (Denmark)

    Welnicka, Katarzyna

    Analysis and processing of 3D digital shapes is a significant research area with numerous medical, industrial, and entertainment applications which has gained enormously in importance as optical scanning modalities have started to make acquired 3D geometry commonplace. The area holds many...... challenges. One such challenge, which is addressed in this thesis, is to develop computational methods for classifying shapes which are in agreement with the human way of understanding and classifying shapes. In this dissertation we first present a shape descriptor based on the process of diffusion...

  4. Management of Microbiologically Influenced Corrosion in Risk Based Inspection analysis

    DEFF Research Database (Denmark)

    Skovhus, Torben Lund; Hillier, Elizabeth; Andersen, Erlend S.

    in the offshore industry as a means to justify the inspection strategy adopted. The RBI analysis is a decision-making technique that enables asset managers to identify the risk related to failure of their most critical systems and components, with an effect on safety, environmental and business related issues...... and discussed. From a risk perspective, MIC is not satisfactorily assessed by the current models and the models lack a proper view of the MIC threat. Therefore, a review of known parameters that affect MIC is presented. The mapping and identification of parameters is based on the review of past models...

  5. Measurement Uncertainty Analysis of the Strain Gauge Based Stabilographic Platform

    Directory of Open Access Journals (Sweden)

    Walendziuk Wojciech

    2014-08-01

    Full Text Available The present article describes constructing a stabilographic platform which records a standing patient’s deflection from their point of balance. The constructed device is composed of a toughen glass slab propped with 4 force sensors. Power transducers are connected to the measurement system based on a 24-bit ADC transducer which acquires slight body movements of a patient. The data is then transferred to the computer in real time and data analysis is conducted. The article explains the principle of operation as well as the algorithm of measurement uncertainty for the COP (Centre of Pressure surface (x, y.

  6. AMATCHMETHOD BASED ON LATENT SEMANTIC ANALYSIS FOR EARTHQUAKEHAZARD EMERGENCY PLAN

    Directory of Open Access Journals (Sweden)

    D. Sun

    2017-09-01

    Full Text Available The structure of the emergency plan on earthquake is complex, and it’s difficult for decision maker to make a decision in a short time. To solve the problem, this paper presents a match method based on Latent Semantic Analysis (LSA. After the word segmentation preprocessing of emergency plan, we carry out keywords extraction according to the part-of-speech and the frequency of words. Then through LSA, we map the documents and query information to the semantic space, and calculate the correlation of documents and queries by the relation between vectors. The experiments results indicate that the LSA can improve the accuracy of emergency plan retrieval efficiently.

  7. [A new calibration transfer method based on target factor analysis].

    Science.gov (United States)

    Wang, Yan-bin; Yuan, Hong-fu; Lu, Wan-zhen

    2005-03-01

    A new calibration transfer method based on target factor analysis is proposed.The performance of the new method compared with the piecewise direct standardization method. This method was applied to two data sets, of which one is a simulation data set, and the other is an NIR data set composed of benzene, toluene, xylene and isooctane. The results obtained with this new method are at least as well as those obtained by PDS with the biggest improvement occurring when the spectra have some non-linear responses.

  8. Electromagnetic fields from mobile phone base station - variability analysis.

    Science.gov (United States)

    Bienkowski, Pawel; Zubrzak, Bartlomiej

    2015-09-01

    The article describes the character of electromagnetic field (EMF) in mobile phone base station (BS) surroundings and its variability in time with an emphasis on the measurement difficulties related to its pulse and multi-frequency nature. Work also presents long-term monitoring measurements performed recently in different locations in Poland - small city with dispersed building development and in major polish city - dense urban area. Authors tried to determine the trends in changing of EMF spectrum analyzing daily changes of measured EMF levels in those locations. Research was performed using selective electromagnetic meters and also EMF meter with spectrum analysis.

  9. Analysis, optimization and implementation of a variable retardance based polarimeter

    Directory of Open Access Journals (Sweden)

    Moreno I.

    2010-06-01

    Full Text Available We present a comprehensive analysis, optimization and implementation of a Stokes polarimeter based on two liquid crystals acting as variable retarders. For the optimization process, the Conditional Number or the Equally Weighted Variance indicators are applied and compared as a function of different number of polarization analyzers. Moreover, some of the optimized polarimeter configurations are experimentally implemented and the influence of small experimental deviations from the optimized configuration values on the amplification of the Stokes component error is also studied. Some experimental results obtained by using the implemented polarimeters, when measuring different incidence states of polarization, are provided.

  10. Quantitative analysis of lead in polysulfide-based impression material

    Directory of Open Access Journals (Sweden)

    Aparecida Silva Braga

    2007-06-01

    Full Text Available Permlastic® is a polysulfide-based impression material widely used by dentists in Brazil. It is composed of a base paste and a catalyzer containing lead dioxide. The high toxicity of lead to humans is ground for much concern, since it can attack various systems and organs. The present study involved a quantitative analysis of the concentration of lead in the material Permlastic®. The lead was determined by plasma-induced optical emission spectrometry (Varian model Vista. The percentages of lead found in the two analyzed lots were 38.1 and 40.8%. The lead concentrations in the material under study were high, but the product’s packaging contained no information about these concentrations.

  11. Linear feature selection in texture analysis - A PLS based method

    DEFF Research Database (Denmark)

    Marques, Joselene; Igel, Christian; Lillholm, Martin

    2013-01-01

    We present a texture analysis methodology that combined uncommitted machine-learning techniques and partial least square (PLS) in a fully automatic framework. Our approach introduces a robust PLS-based dimensionality reduction (DR) step to specifically address outliers and high-dimensional feature......, which first applied a PLS regression to rank the features and then defined the best number of features to retain in the model by an iterative learning phase. The outliers in the dataset, that could inflate the number of selected features, were eliminated by a pre-processing step. To cope...... and considering all CV groups, the methods selected 36 % of the original features available. The diagnosis evaluation reached a generalization area-under-the-ROC curve of 0.92, which was higher than established cartilage-based markers known to relate to OA diagnosis....

  12. Content and user-based music visual analysis

    Science.gov (United States)

    Guo, Xiaochun; Tang, Lei

    2015-12-01

    In recent years, people's ability to collect music got enhanced greatly. Many people who prefer listening music offline even stored thousands of music on their local storage or portable device. However, their ability to deal with music information has not been improved accordingly, which results in two problems. One is how to find out the favourite songs from large music dataset and satisfy different individuals. The other one is how to compose a play list quickly. To solve these problems, the authors proposed a content and user-based music visual analysis approach. We first developed a new recommendation algorithm based on the content of music and user's behaviour, which satisfy individual's preference. Then, we make use of visualization and interaction tools to illustrate the relationship between songs and help people compose a suitable play list. At the end of this paper, a survey is mentioned to show that our system is available and effective.

  13. Independent Component Analysis applied to Ground-based observations

    Science.gov (United States)

    Martins-Filho, Walter; Griffith, Caitlin; Pearson, Kyle; Waldmann, Ingo; Alvarez-Candal, Alvaro; Zellem, Robert Thomas

    2018-01-01

    Transit measurements of Jovian-sized exoplanetary atmospheres allow one to study the composition of exoplanets, largely independent of the planet’s temperature profile. However, measurements of hot-Jupiter transits must archive a level of accuracy in the flux to determine the spectral modulation of the exoplanetary atmosphere. To accomplish this level of precision, we need to extract systematic errors, and, for ground-based measurements, the effects of Earth’s atmosphere, from signal due to the exoplanet, which is several orders of magnitude smaller. The effects of the terrestrial atmosphere and some of the time-dependent systematic errors of ground-based transit measurements are treated mainly by dividing the host star by a reference star at each wavelength and time step of the transit. Recently, Independent Component Analysis (ICA) have been used to remove systematics effects from the raw data of space-based observations (Waldmann, 2014, 2012; Morello et al., 2016, 2015). ICA is a statistical method born from the ideas of the blind-source separations studies, which can be used to de-trend several independent source signals of a data set (Hyvarinen and Oja, 2000). This technique requires no additional prior knowledge of the data set. In addition, this technique has the advantage of requiring no reference star. Here we apply the ICA to ground-based photometry of the exoplanet XO-2b recorded by the 61” Kuiper Telescope and compare the results of the ICA to those of a previous analysis from Zellem et al. (2015), which does not use ICA. We also simulate the effects of various conditions (concerning the systematic errors, noise and the stability of object on the detector) to determine the conditions under which an ICA can be used with high precision to extract the light curve of exoplanetary photometry measurements

  14. Phishing Detection: Analysis of Visual Similarity Based Approaches

    Directory of Open Access Journals (Sweden)

    Ankit Kumar Jain

    2017-01-01

    Full Text Available Phishing is one of the major problems faced by cyber-world and leads to financial losses for both industries and individuals. Detection of phishing attack with high accuracy has always been a challenging issue. At present, visual similarities based techniques are very useful for detecting phishing websites efficiently. Phishing website looks very similar in appearance to its corresponding legitimate website to deceive users into believing that they are browsing the correct website. Visual similarity based phishing detection techniques utilise the feature set like text content, text format, HTML tags, Cascading Style Sheet (CSS, image, and so forth, to make the decision. These approaches compare the suspicious website with the corresponding legitimate website by using various features and if the similarity is greater than the predefined threshold value then it is declared phishing. This paper presents a comprehensive analysis of phishing attacks, their exploitation, some of the recent visual similarity based approaches for phishing detection, and its comparative study. Our survey provides a better understanding of the problem, current solution space, and scope of future research to deal with phishing attacks efficiently using visual similarity based approaches.

  15. Semiconductor product analysis challenges based on the 1999 ITRS

    International Nuclear Information System (INIS)

    Joseph, Thomas W.; Anderson, Richard E.; Gilfeather, Glen; LeClaire, Carole; Yim, Daniel

    2001-01-01

    One of the most significant challenges for technology characterization and failure analysis is to keep instrumentation and techniques in step with the development of technology itself. Not only are dimensions shrinking and new materials being employed, but the rate of change is increasing. According to the 1999 International Technology Roadmap for Semiconductors, 'The number and difficulty of the technical challenges continue to increase as technology moves forward'. It could be argued that technology cannot be developed without appropriate analytical techniques; nevertheless while much effort is being directed at materials and processes, only a small proportion is being directed at analysis. Whereas previous versions of the Semiconductor Industry Association roadmap contained a small number of implicit references to characterization and analysis, the 1999 ITRS contains many explicit references. It is clear that characterization is now woven through the roadmap, and technology developers in all areas appreciate the fact that new instrumentation and techniques will be required to sustain the rate of development the semiconductor industry has seen in recent years. Late in 1999, a subcommittee of the Sematech Product Analysis Forum (PAF) reviewed the ITRS and identified a 'top-ten' list of challenges which the failure analysis community will face as present technologies are extended and future technologies are developed. This paper discusses the PAF top-ten list of challenges, which is based primarily on the Difficult Challenges tables from each ITRS working group. Eight of the top-ten are challenges of significant technical magnitude; only two could be considered non-technical in nature. Most of these challenges cut across several working group areas and could be considered common threads in the roadmap, ranging from fault simulation and modeling to imaging small features, from electrical defect isolation to deprocessing. While evolutionary changes can be anticipated

  16. AntDAS: Automatic Data Analysis Strategy for UPLC-QTOF-Based Nontargeted Metabolic Profiling Analysis.

    Science.gov (United States)

    Fu, Hai-Yan; Guo, Xiao-Ming; Zhang, Yue-Ming; Song, Jing-Jing; Zheng, Qing-Xia; Liu, Ping-Ping; Lu, Peng; Chen, Qian-Si; Yu, Yong-Jie; She, Yuanbin

    2017-10-17

    High-quality data analysis methodology remains a bottleneck for metabolic profiling analysis based on ultraperformance liquid chromatography-quadrupole time-of-flight mass spectrometry. The present work aims to address this problem by proposing a novel data analysis strategy wherein (1) chromatographic peaks in the UPLC-QTOF data set are automatically extracted by using an advanced multiscale Gaussian smoothing-based peak extraction strategy; (2) a peak annotation stage is used to cluster fragment ions that belong to the same compound. With the aid of high-resolution mass spectrometer, (3) a time-shift correction across the samples is efficiently performed by a new peak alignment method; (4) components are registered by using a newly developed adaptive network searching algorithm; (5) statistical methods, such as analysis of variance and hierarchical cluster analysis, are then used to identify the underlying marker compounds; finally, (6) compound identification is performed by matching the extracted peak information, involving high-precision m/z and retention time, against our compound library containing more than 500 plant metabolites. A manually designed mixture of 18 compounds is used to evaluate the performance of the method, and all compounds are detected under various concentration levels. The developed method is comprehensively evaluated by an extremely complex plant data set containing more than 2000 components. Results indicate that the performance of the developed method is comparable with the XCMS. The MATLAB GUI code is available from http://software.tobaccodb.org/software/antdas .

  17. Flood Risk Assessment Based On Security Deficit Analysis

    Science.gov (United States)

    Beck, J.; Metzger, R.; Hingray, B.; Musy, A.

    Risk is a human perception: a given risk may be considered as acceptable or unac- ceptable depending on the group that has to face that risk. Flood risk analysis of- ten estimates economic losses from damages, but neglects the question of accept- able/unacceptable risk. With input from land use managers, politicians and other stakeholders, risk assessment based on security deficit analysis determines objects with unacceptable risk and their degree of security deficit. Such a risk assessment methodology, initially developed by the Swiss federal authorities, is illustrated by its application on a reach of the Alzette River (Luxembourg) in the framework of the IRMA-SPONGE FRHYMAP project. Flood risk assessment always involves a flood hazard analysis, an exposed object vulnerability analysis, and an analysis combing the results of these two previous analyses. The flood hazard analysis was done with the quasi-2D hydraulic model FldPln to produce flood intensity maps. Flood intensity was determined by the water height and velocity. Object data for the vulnerability analysis, provided by the Luxembourg government, were classified according to their potential damage. Potential damage is expressed in terms of direct, human life and secondary losses. A thematic map was produced to show the object classification. Protection goals were then attributed to the object classes. Protection goals are assigned in terms of an acceptable flood intensity for a certain flood frequency. This is where input from land use managers and politicians comes into play. The perception of risk in the re- gion or country influences the protection goal assignment. Protection goals as used in Switzerland were used in this project. Thematic maps showing the protection goals of each object in the case study area for a given flood frequency were produced. Com- parison between an object's protection goal and the intensity of the flood that touched the object determine the acceptability of the risk and the

  18. Streaming Support for Data Intensive Cloud-Based Sequence Analysis

    Science.gov (United States)

    Issa, Shadi A.; Kienzler, Romeo; El-Kalioby, Mohamed; Tonellato, Peter J.; Wall, Dennis; Bruggmann, Rémy; Abouelhoda, Mohamed

    2013-01-01

    Cloud computing provides a promising solution to the genomics data deluge problem resulting from the advent of next-generation sequencing (NGS) technology. Based on the concepts of “resources-on-demand” and “pay-as-you-go”, scientists with no or limited infrastructure can have access to scalable and cost-effective computational resources. However, the large size of NGS data causes a significant data transfer latency from the client's site to the cloud, which presents a bottleneck for using cloud computing services. In this paper, we provide a streaming-based scheme to overcome this problem, where the NGS data is processed while being transferred to the cloud. Our scheme targets the wide class of NGS data analysis tasks, where the NGS sequences can be processed independently from one another. We also provide the elastream package that supports the use of this scheme with individual analysis programs or with workflow systems. Experiments presented in this paper show that our solution mitigates the effect of data transfer latency and saves both time and cost of computation. PMID:23710461

  19. Bayesian analysis of physiologically based toxicokinetic and toxicodynamic models.

    Science.gov (United States)

    Hack, C Eric

    2006-04-17

    Physiologically based toxicokinetic (PBTK) and toxicodynamic (TD) models of bromate in animals and humans would improve our ability to accurately estimate the toxic doses in humans based on available animal studies. These mathematical models are often highly parameterized and must be calibrated in order for the model predictions of internal dose to adequately fit the experimentally measured doses. Highly parameterized models are difficult to calibrate and it is difficult to obtain accurate estimates of uncertainty or variability in model parameters with commonly used frequentist calibration methods, such as maximum likelihood estimation (MLE) or least squared error approaches. The Bayesian approach called Markov chain Monte Carlo (MCMC) analysis can be used to successfully calibrate these complex models. Prior knowledge about the biological system and associated model parameters is easily incorporated in this approach in the form of prior parameter distributions, and the distributions are refined or updated using experimental data to generate posterior distributions of parameter estimates. The goal of this paper is to give the non-mathematician a brief description of the Bayesian approach and Markov chain Monte Carlo analysis, how this technique is used in risk assessment, and the issues associated with this approach.

  20. Analysis of Android Device-Based Solutions for Fall Detection.

    Science.gov (United States)

    Casilari, Eduardo; Luque, Rafael; Morón, María-José

    2015-07-23

    Falls are a major cause of health and psychological problems as well as hospitalization costs among older adults. Thus, the investigation on automatic Fall Detection Systems (FDSs) has received special attention from the research community during the last decade. In this area, the widespread popularity, decreasing price, computing capabilities, built-in sensors and multiplicity of wireless interfaces of Android-based devices (especially smartphones) have fostered the adoption of this technology to deploy wearable and inexpensive architectures for fall detection. This paper presents a critical and thorough analysis of those existing fall detection systems that are based on Android devices. The review systematically classifies and compares the proposals of the literature taking into account different criteria such as the system architecture, the employed sensors, the detection algorithm or the response in case of a fall alarms. The study emphasizes the analysis of the evaluation methods that are employed to assess the effectiveness of the detection process. The review reveals the complete lack of a reference framework to validate and compare the proposals. In addition, the study also shows that most research works do not evaluate the actual applicability of the Android devices (with limited battery and computing resources) to fall detection solutions.

  1. Research on cloud-based remote measurement and analysis system

    Science.gov (United States)

    Gao, Zhiqiang; He, Lingsong; Su, Wei; Wang, Can; Zhang, Changfan

    2015-02-01

    The promising potential of cloud computing and its convergence with technologies such as cloud storage, cloud push, mobile computing allows for creation and delivery of newer type of cloud service. Combined with the thought of cloud computing, this paper presents a cloud-based remote measurement and analysis system. This system mainly consists of three parts: signal acquisition client, web server deployed on the cloud service, and remote client. This system is a special website developed using asp.net and Flex RIA technology, which solves the selective contradiction between two monitoring modes, B/S and C/S. This platform supplies customer condition monitoring and data analysis service by Internet, which was deployed on the cloud server. Signal acquisition device is responsible for data (sensor data, audio, video, etc.) collection and pushes the monitoring data to the cloud storage database regularly. Data acquisition equipment in this system is only conditioned with the function of data collection and network function such as smartphone and smart sensor. This system's scale can adjust dynamically according to the amount of applications and users, so it won't cause waste of resources. As a representative case study, we developed a prototype system based on Ali cloud service using the rotor test rig as the research object. Experimental results demonstrate that the proposed system architecture is feasible.

  2. Principle-based concept analysis: intentionality in holistic nursing theories.

    Science.gov (United States)

    Aghebati, Nahid; Mohammadi, Eesa; Ahmadi, Fazlollah; Noaparast, Khosrow Bagheri

    2015-03-01

    This is a report of a principle-based concept analysis of intentionality in holistic nursing theories. A principle-based concept analysis method was used to analyze seven holistic theories. The data included eight books and 31 articles (1998-2011), which were retrieved through MEDLINE and CINAHL. Erickson, Kriger, Parse, Watson, and Zahourek define intentionality as a capacity, a focused consciousness, and a pattern of human being. Rogers and Newman do not explicitly mention intentionality; however, they do explain pattern and consciousness (epistemology). Intentionality has been operationalized as a core concept of nurse-client relationships (pragmatic). The theories are consistent on intentionality as a noun and as an attribute of the person-intentionality is different from intent and intention (linguistic). There is ambiguity concerning the boundaries between intentionality and consciousness (logic). Theoretically, intentionality is an evolutionary capacity to integrate human awareness and experience. Because intentionality is an individualized concept, we introduced it as "a matrix of continuous known changes" that emerges in two forms: as a capacity of human being and as a capacity of transpersonal caring. This study has produced a theoretical definition of intentionality and provides a foundation for future research to further investigate intentionality to better delineate its boundaries. © The Author(s) 2014.

  3. Nonlinear Process Fault Diagnosis Based on Serial Principal Component Analysis.

    Science.gov (United States)

    Deng, Xiaogang; Tian, Xuemin; Chen, Sheng; Harris, Chris J

    2018-03-01

    Many industrial processes contain both linear and nonlinear parts, and kernel principal component analysis (KPCA), widely used in nonlinear process monitoring, may not offer the most effective means for dealing with these nonlinear processes. This paper proposes a new hybrid linear-nonlinear statistical modeling approach for nonlinear process monitoring by closely integrating linear principal component analysis (PCA) and nonlinear KPCA using a serial model structure, which we refer to as serial PCA (SPCA). Specifically, PCA is first applied to extract PCs as linear features, and to decompose the data into the PC subspace and residual subspace (RS). Then, KPCA is performed in the RS to extract the nonlinear PCs as nonlinear features. Two monitoring statistics are constructed for fault detection, based on both the linear and nonlinear features extracted by the proposed SPCA. To effectively perform fault identification after a fault is detected, an SPCA similarity factor method is built for fault recognition, which fuses both the linear and nonlinear features. Unlike PCA and KPCA, the proposed method takes into account both linear and nonlinear PCs simultaneously, and therefore, it can better exploit the underlying process's structure to enhance fault diagnosis performance. Two case studies involving a simulated nonlinear process and the benchmark Tennessee Eastman process demonstrate that the proposed SPCA approach is more effective than the existing state-of-the-art approach based on KPCA alone, in terms of nonlinear process fault detection and identification.

  4. Applying model analysis to a resource-based analysis of the Force and Motion Conceptual Evaluation

    Directory of Open Access Journals (Sweden)

    Trevor I. Smith

    2014-07-01

    Full Text Available Previously, we analyzed the Force and Motion Conceptual Evaluation in terms of a resources-based model that allows for clustering of questions so as to provide useful information on how students correctly or incorrectly reason about physics. In this paper, we apply model analysis to show that the associated model plots provide more information regarding the results of investigations using these question clusters than normalized gain graphs. We provide examples from two different institutions to show how the use of model analysis with our redefined clusters can provide previously hidden insight into the effectiveness of instruction.

  5. Heating Analysis in Constant-pressure Hydraulic System based on Energy Analysis

    Science.gov (United States)

    Wu, Chao; Xu, Cong; Mao, Xuyao; Li, Bin; Hu, Junhua; Liu, Yiou

    2017-12-01

    Hydraulic systems are widely used in industrial applications, but the problem of heating has become an important reason to restrict the promotion of hydraulic technology. The high temperature, will seriously affect the operation of the hydraulic system, even cause stuck and other serious failure. Based on the analysis of the heat damage of the hydraulic system, this paper gives the reasons for this problem, and it is showed by the application that the energy analysis can accurately locate the main reasons for the heating of the hydraulic system, which can give strong practical guidance.

  6. A Web-Based Development Environment for Collaborative Data Analysis

    CERN Document Server

    Erdmann, M; Glaser, C; Klingebiel, D; Komm, M; Müller, G; Rieger, M; Steggemann, J; Urban, M; Winchen, T

    2014-01-01

    Visual Physics Analysis (VISPA) is a web-based development environment addressing high energy and astroparticle physics. It covers the entire analysis spectrum from the design and validation phase to the execution of analyses and the visualization of results. VISPA provides a graphical steering of the analysis ow, which consists of self-written, re-usable Python and C++ modules for more demanding tasks. All common operating systems are supported since a standard internet browser is the only software requirement for users. Even access via mobile and touch-compatible devices is possible. In this contribution, we present the most recent developments of our web application concerning technical, state-of-the-art approaches as well as practical experiences. One of the key features is the use of workspaces, i.e. user-congurable connections to remote machines supplying resources and local le access. Thereby, workspaces enable the management of data, computing resources (e.g. remote clusters or computing grids), and a...

  7. Coordinate-based versus structural approaches to brain image analysis.

    Science.gov (United States)

    Mangin, J-F; Rivière, D; Coulon, O; Poupon, C; Cachia, A; Cointepas, Y; Poline, J-B; Le Bihan, D; Régis, J; Papadopoulos-Orfanos, D

    2004-02-01

    A basic issue in neurosciences is to look for possible relationships between brain architecture and cognitive models. The lack of architectural information in magnetic resonance images, however, has led the neuroimaging community to develop brain mapping strategies based on various coordinate systems without accurate architectural content. Therefore, the relationships between architectural and functional brain organizations are difficult to study when analyzing neuroimaging experiments. This paper advocates that the design of new brain image analysis methods inspired by the structural strategies often used in computer vision may provide better ways to address these relationships. The key point underlying this new framework is the conversion of the raw images into structural representations before analysis. These representations are made up of data-driven elementary features like activated clusters, cortical folds or fiber bundles. Two classes of methods are introduced. Inference of structural models via matching across a set of individuals is described first. This inference problem is illustrated by the group analysis of functional statistical parametric maps (SPMs). Then, the matching of new individual data with a priori known structural models is described, using the recognition of the cortical sulci as a prototypical example.

  8. A Web-Based Development Environment for Collaborative Data Analysis

    Science.gov (United States)

    Erdmann, M.; Fischer, R.; Glaser, C.; Klingebiel, D.; Komm, M.; Müller, G.; Rieger, M.; Steggemann, J.; Urban, M.; Winchen, T.

    2014-06-01

    Visual Physics Analysis (VISPA) is a web-based development environment addressing high energy and astroparticle physics. It covers the entire analysis spectrum from the design and validation phase to the execution of analyses and the visualization of results. VISPA provides a graphical steering of the analysis flow, which consists of self-written, re-usable Python and C++ modules for more demanding tasks. All common operating systems are supported since a standard internet browser is the only software requirement for users. Even access via mobile and touch-compatible devices is possible. In this contribution, we present the most recent developments of our web application concerning technical, state-of-the-art approaches as well as practical experiences. One of the key features is the use of workspaces, i.e. user-configurable connections to remote machines supplying resources and local file access. Thereby, workspaces enable the management of data, computing resources (e.g. remote clusters or computing grids), and additional software either centralized or individually. We further report on the results of an application with more than 100 third-year students using VISPA for their regular particle physics exercises during the winter term 2012/13. Besides the ambition to support and simplify the development cycle of physics analyses, new use cases such as fast, location-independent status queries, the validation of results, and the ability to share analyses within worldwide collaborations with a single click become conceivable.

  9. A Web-Based Development Environment for Collaborative Data Analysis

    International Nuclear Information System (INIS)

    Erdmann, M; Fischer, R; Glaser, C; Klingebiel, D; Müller, G; Rieger, M; Urban, M; Winchen, T; Komm, M; Steggemann, J

    2014-01-01

    Visual Physics Analysis (VISPA) is a web-based development environment addressing high energy and astroparticle physics. It covers the entire analysis spectrum from the design and validation phase to the execution of analyses and the visualization of results. VISPA provides a graphical steering of the analysis flow, which consists of self-written, re-usable Python and C++ modules for more demanding tasks. All common operating systems are supported since a standard internet browser is the only software requirement for users. Even access via mobile and touch-compatible devices is possible. In this contribution, we present the most recent developments of our web application concerning technical, state-of-the-art approaches as well as practical experiences. One of the key features is the use of workspaces, i.e. user-configurable connections to remote machines supplying resources and local file access. Thereby, workspaces enable the management of data, computing resources (e.g. remote clusters or computing grids), and additional software either centralized or individually. We further report on the results of an application with more than 100 third-year students using VISPA for their regular particle physics exercises during the winter term 2012/13. Besides the ambition to support and simplify the development cycle of physics analyses, new use cases such as fast, location-independent status queries, the validation of results, and the ability to share analyses within worldwide collaborations with a single click become conceivable

  10. Asymptotic performance of regularized quadratic discriminant analysis based classifiers

    KAUST Repository

    Elkhalil, Khalil

    2017-12-13

    This paper carries out a large dimensional analysis of the standard regularized quadratic discriminant analysis (QDA) classifier designed on the assumption that data arise from a Gaussian mixture model. The analysis relies on fundamental results from random matrix theory (RMT) when both the number of features and the cardinality of the training data within each class grow large at the same pace. Under some mild assumptions, we show that the asymptotic classification error converges to a deterministic quantity that depends only on the covariances and means associated with each class as well as the problem dimensions. Such a result permits a better understanding of the performance of regularized QDA and can be used to determine the optimal regularization parameter that minimizes the misclassification error probability. Despite being valid only for Gaussian data, our theoretical findings are shown to yield a high accuracy in predicting the performances achieved with real data sets drawn from popular real data bases, thereby making an interesting connection between theory and practice.

  11. Glyph-Based Video Visualization for Semen Analysis

    KAUST Repository

    Duffy, Brian

    2015-08-01

    © 2013 IEEE. The existing efforts in computer assisted semen analysis have been focused on high speed imaging and automated image analysis of sperm motility. This results in a large amount of data, and it is extremely challenging for both clinical scientists and researchers to interpret, compare and correlate the multidimensional and time-varying measurements captured from video data. In this work, we use glyphs to encode a collection of numerical measurements taken at a regular interval and to summarize spatio-temporal motion characteristics using static visual representations. The design of the glyphs addresses the needs for (a) encoding some 20 variables using separable visual channels, (b) supporting scientific observation of the interrelationships between different measurements and comparison between different sperm cells and their flagella, and (c) facilitating the learning of the encoding scheme by making use of appropriate visual abstractions and metaphors. As a case study, we focus this work on video visualization for computer-aided semen analysis, which has a broad impact on both biological sciences and medical healthcare. We demonstrate that glyph-based visualization can serve as a means of external memorization of video data as well as an overview of a large set of spatiotemporal measurements. It enables domain scientists to make scientific observation in a cost-effective manner by reducing the burden of viewing videos repeatedly, while providing them with a new visual representation for conveying semen statistics.

  12. SVM-based glioma grading. Optimization by feature reduction analysis

    Energy Technology Data Exchange (ETDEWEB)

    Zoellner, Frank G.; Schad, Lothar R. [University Medical Center Mannheim, Heidelberg Univ., Mannheim (Germany). Computer Assisted Clinical Medicine; Emblem, Kyrre E. [Massachusetts General Hospital, Charlestown, A.A. Martinos Center for Biomedical Imaging, Boston MA (United States). Dept. of Radiology; Harvard Medical School, Boston, MA (United States); Oslo Univ. Hospital (Norway). The Intervention Center

    2012-11-01

    We investigated the predictive power of feature reduction analysis approaches in support vector machine (SVM)-based classification of glioma grade. In 101 untreated glioma patients, three analytic approaches were evaluated to derive an optimal reduction in features; (i) Pearson's correlation coefficients (PCC), (ii) principal component analysis (PCA) and (iii) independent component analysis (ICA). Tumor grading was performed using a previously reported SVM approach including whole-tumor cerebral blood volume (CBV) histograms and patient age. Best classification accuracy was found using PCA at 85% (sensitivity = 89%, specificity = 84%) when reducing the feature vector from 101 (100-bins rCBV histogram + age) to 3 principal components. In comparison, classification accuracy by PCC was 82% (89%, 77%, 2 dimensions) and 79% by ICA (87%, 75%, 9 dimensions). For improved speed (up to 30%) and simplicity, feature reduction by all three methods provided similar classification accuracy to literature values ({proportional_to}87%) while reducing the number of features by up to 98%. (orig.)

  13. Global regulatory roles of the cAMP/PKA pathway revealed by phenotypic, transcriptomic and phosphoproteomic analyses in a null mutant of the PKA catalytic subunit in Candida albicans.

    Science.gov (United States)

    Cao, Chengjun; Wu, Mei; Bing, Jian; Tao, Li; Ding, Xuefen; Liu, Xiaoyun; Huang, Guanghua

    2017-07-01

    The conserved cAMP-dependent protein kinase (PKA) plays critical roles in the regulation of morphological transitions and virulence in the human fungal pathogen Candida albicans. It has long been thought that the PKA catalytic subunit is essential for cell viability in this fungus. Paradoxically, the single adenylyl cyclase-encoding gene, CYR1, which is required for the production of cAMP in C. albicans, is not essential for cell growth. Here, a double mutant of TPK1 and TPK2 (tpk2/tpk2 tpk1/tpk1, t2t1), which encode two isoforms of the PKA catalytic subunit was successfully generated, suggesting that this subunit is not essential for cell viability. Inactivation of the PKA catalytic subunit blocked filamentation and dramatically attenuated white-to-opaque switching, but promoted sexual mating. Comparative transcriptomic analyses demonstrated that the t2t1 and cyr1/cyr1 mutants exhibited similar global gene expression profiles. Compared with the WT strain, the general transcriptional activity and metabolism were significantly decreased in both the t2t1 and cyr1/cyr1 mutants. Using combined phosphoproteomic and bioinformatic analyses, we identified 181 potential PKA phosphorylation targets, which represent 148 unique proteins involved in a wide spectrum of biological processes. The study sheds new insights into the global regulatory features of the cAMP/PKA pathway in C. albicans. © 2017 John Wiley & Sons Ltd.

  14. Cost Risk Analysis Based on Perception of the Engineering Process

    Science.gov (United States)

    Dean, Edwin B.; Wood, Darrell A.; Moore, Arlene A.; Bogart, Edward H.

    1986-01-01

    In most cost estimating applications at the NASA Langley Research Center (LaRC), it is desirable to present predicted cost as a range of possible costs rather than a single predicted cost. A cost risk analysis generates a range of cost for a project and assigns a probability level to each cost value in the range. Constructing a cost risk curve requires a good estimate of the expected cost of a project. It must also include a good estimate of expected variance of the cost. Many cost risk analyses are based upon an expert's knowledge of the cost of similar projects in the past. In a common scenario, a manager or engineer, asked to estimate the cost of a project in his area of expertise, will gather historical cost data from a similar completed project. The cost of the completed project is adjusted using the perceived technical and economic differences between the two projects. This allows errors from at least three sources. The historical cost data may be in error by some unknown amount. The managers' evaluation of the new project and its similarity to the old project may be in error. The factors used to adjust the cost of the old project may not correctly reflect the differences. Some risk analyses are based on untested hypotheses about the form of the statistical distribution that underlies the distribution of possible cost. The usual problem is not just to come up with an estimate of the cost of a project, but to predict the range of values into which the cost may fall and with what level of confidence the prediction is made. Risk analysis techniques that assume the shape of the underlying cost distribution and derive the risk curve from a single estimate plus and minus some amount usually fail to take into account the actual magnitude of the uncertainty in cost due to technical factors in the project itself. This paper addresses a cost risk method that is based on parametric estimates of the technical factors involved in the project being costed. The engineering

  15. Technoeconomic analysis of a biomass based district heating system

    International Nuclear Information System (INIS)

    Zhang, H.; Ugursal, V.I.; Fung, A.

    2005-01-01

    This paper discussed a proposed biomass-based district heating system to be built for the Pictou Landing First Nation Community in Nova Scotia. The community centre consists of 6 buildings and a connecting arcade. The methodology used to size and design heating, ventilating and air conditioning (HVAC) systems, as well as biomass district energy systems (DES) were discussed. Annual energy requirements and biomass fuel consumption predictions were presented, along with cost estimates. A comparative assessment of the system with that of a conventional oil fired system was also conducted. It was suggested that the design and analysis methodology could be used for any similar application. The buildings were modelled and simulated using the Hourly Analysis Program (HAP), a detailed 2-in-1 software program which can be used both for HVAC system sizing and building energy consumption estimation. A techno-economics analysis was conducted to justify the viability of the biomass combustion system. Heating load calculations were performed assuming that the thermostat was set constantly at 22 degrees C. Community centre space heating loads due to individual envelope components for 3 different scenarios were summarized, as the design architecture for the buildings was not yet finalized. It was suggested that efforts should be made to ensure air-tightness and insulation levels of the interior arcade glass wall. A hydronic distribution system with baseboard space heating units was selected, comprising of a woodchip boiler, hot water distribution system, convective heating units and control systems. The community has its own logging operation which will provide the wood fuel required by the proposed system. An outline of the annual allowable harvest covered by the Pictou Landing Forestry Management Plan was presented, with details of proposed wood-chippers for the creation of biomass. It was concluded that the woodchip combustion system is economically preferable to the

  16. Overview description of the base scenario derived from FEP analysis

    International Nuclear Information System (INIS)

    Locke, J.; Bailey, L.

    1998-01-01

    , subsequent evolution and the processes affecting radionuclide transport for the groundwater and gas pathways. This report uses the conceptual models developed from the FEP analysis to present a description of the base scenario, in terms of the processes to be represented in detailed models. This report does not present an assessment of the base scenario, but rather seeks to provide a summary of those features, events and processes that should be represented, at an appropriate level of detail, within numerical models. The requirements for the development of appropriate models for representing the base scenario are described in an underlying report within the model development document suite. (author)

  17. Variance-based sensitivity analysis for wastewater treatment plant modelling.

    Science.gov (United States)

    Cosenza, Alida; Mannina, Giorgio; Vanrolleghem, Peter A; Neumann, Marc B

    2014-02-01

    Global sensitivity analysis (GSA) is a valuable tool to support the use of mathematical models that characterise technical or natural systems. In the field of wastewater modelling, most of the recent applications of GSA use either regression-based methods, which require close to linear relationships between the model outputs and model factors, or screening methods, which only yield qualitative results. However, due to the characteristics of membrane bioreactors (MBR) (non-linear kinetics, complexity, etc.) there is an interest to adequately quantify the effects of non-linearity and interactions. This can be achieved with variance-based sensitivity analysis methods. In this paper, the Extended Fourier Amplitude Sensitivity Testing (Extended-FAST) method is applied to an integrated activated sludge model (ASM2d) for an MBR system including microbial product formation and physical separation processes. Twenty-one model outputs located throughout the different sections of the bioreactor and 79 model factors are considered. Significant interactions among the model factors are found. Contrary to previous GSA studies for ASM models, we find the relationship between variables and factors to be non-linear and non-additive. By analysing the pattern of the variance decomposition along the plant, the model factors having the highest variance contributions were identified. This study demonstrates the usefulness of variance-based methods in membrane bioreactor modelling where, due to the presence of membranes and different operating conditions than those typically found in conventional activated sludge systems, several highly non-linear effects are present. Further, the obtained results highlight the relevant role played by the modelling approach for MBR taking into account simultaneously biological and physical processes. © 2013.

  18. Cloud-based data-proximate visualization and analysis

    Science.gov (United States)

    Fisher, Ward

    2017-04-01

    The rise in cloud computing, coupled with the growth of "Big Data", has lead to a migration away from local scientific data storage. The increasing size of remote scientific data sets increase, however, makes it difficult for scientists to subject them to large-scale analysis and visualization. These large datasets can take an inordinate amount of time to download; subsetting is a potential solution, but subsetting services are not yet ubiquitous. Data providers may also pay steep prices, as many cloud providers meter data based on how much data leaves their cloud service. The solution to this problem is a deceptively simple one; move data analysis and visualization tools to the cloud, so that scientists may perform data-proximate analysis and visualization. This results in increased transfer speeds, while egress costs are lowered or completely eliminated. The challenge now becomes creating tools which are cloud-ready. The solution to this challenge is provided by Application Streaming. This technology allows a program to run entirely on a remote virtual machine while still allowing for interactivity and dynamic visualizations. When coupled with containerization technology such as Docker, we are able to easily deploy legacy analysis and visualization software to the cloud whilst retaining access via a desktop, netbook, a smartphone, or the next generation of hardware, whatever it may be. Unidata has harnessed Application Streaming to provide a cloud-capable version of our visualization software, the Integrated Data Viewer (IDV). This work will examine the challenges associated with adapting the IDV to an application streaming platform, and include a brief discussion of the underlying technologies involved.

  19. Feature-Based Statistical Analysis of Combustion Simulation Data

    Energy Technology Data Exchange (ETDEWEB)

    Bennett, J; Krishnamoorthy, V; Liu, S; Grout, R; Hawkes, E; Chen, J; Pascucci, V; Bremer, P T

    2011-11-18

    We present a new framework for feature-based statistical analysis of large-scale scientific data and demonstrate its effectiveness by analyzing features from Direct Numerical Simulations (DNS) of turbulent combustion. Turbulent flows are ubiquitous and account for transport and mixing processes in combustion, astrophysics, fusion, and climate modeling among other disciplines. They are also characterized by coherent structure or organized motion, i.e. nonlocal entities whose geometrical features can directly impact molecular mixing and reactive processes. While traditional multi-point statistics provide correlative information, they lack nonlocal structural information, and hence, fail to provide mechanistic causality information between organized fluid motion and mixing and reactive processes. Hence, it is of great interest to capture and track flow features and their statistics together with their correlation with relevant scalar quantities, e.g. temperature or species concentrations. In our approach we encode the set of all possible flow features by pre-computing merge trees augmented with attributes, such as statistical moments of various scalar fields, e.g. temperature, as well as length-scales computed via spectral analysis. The computation is performed in an efficient streaming manner in a pre-processing step and results in a collection of meta-data that is orders of magnitude smaller than the original simulation data. This meta-data is sufficient to support a fully flexible and interactive analysis of the features, allowing for arbitrary thresholds, providing per-feature statistics, and creating various global diagnostics such as Cumulative Density Functions (CDFs), histograms, or time-series. We combine the analysis with a rendering of the features in a linked-view browser that enables scientists to interactively explore, visualize, and analyze the equivalent of one terabyte of simulation data. We highlight the utility of this new framework for combustion

  20. Extent of Endoscopic Resection for Anterior Skull Base Tumors: An MRI-Based Volumetric Analysis.

    Science.gov (United States)

    Koszewski, Ian J; Avey, Gregory; Ahmed, Azam; Leonhard, Lucas; Hoffman, Matthew R; McCulloch, Timothy M

    2017-06-01

    Objective  To determine the volume of ventral skull base tumor removed following endoscopic endonasal (EEA) resection using MRI-based volumetric analysis and to evaluate the inter-rater reliability of such analysis. Design  Retrospective case series. Setting  Academic tertiary care hospital. Participants  EEA patients November 2012 to August 2015. Main Outcome Measures  Volumetric analysis of pre- and immediately postoperative MR imaging was performed independently by two investigators. The percentage of total tumor resected was evaluated according to resection goal and tumor type. Results  A total of 39 patients underwent resection. Intraclass correlation coefficients between the raters were 0.9988 for preoperative and 0.9819 for postoperative images. Tumors (and average percentage removed) included 17 nonsecreting pituitary adenomas (95.3%), 8 secreting pituitary adenomas (86.2%), 4 meningiomas (81.6%), 3 olfactory neuroblastomas (100%), 2 craniopharyngiomas (100%), 1 large B-cell lymphoma (90.5%), 1 germ cell neoplasm (48.3), 1 benign fibrous connective tissue mass (93.4%), 1 epidermoid cyst (68.4%), and 1 chordoma (100%). For tumors treated with intent for gross total resection, 96.9 ± 4.8% was removed. Conclusion  EEAs achieved tumor resection rates of ∼97% when total resection was attempted. The radiographic finding of residual tumor is of uncertain clinical significance. The volumetric analysis employed in this study demonstrated high inter-rater reliability and could facilitate further study.

  1. A Novel Multiobjective Evolutionary Algorithm Based on Regression Analysis

    Directory of Open Access Journals (Sweden)

    Zhiming Song

    2015-01-01

    Full Text Available As is known, the Pareto set of a continuous multiobjective optimization problem with m objective functions is a piecewise continuous (m-1-dimensional manifold in the decision space under some mild conditions. However, how to utilize the regularity to design multiobjective optimization algorithms has become the research focus. In this paper, based on this regularity, a model-based multiobjective evolutionary algorithm with regression analysis (MMEA-RA is put forward to solve continuous multiobjective optimization problems with variable linkages. In the algorithm, the optimization problem is modelled as a promising area in the decision space by a probability distribution, and the centroid of the probability distribution is (m-1-dimensional piecewise continuous manifold. The least squares method is used to construct such a model. A selection strategy based on the nondominated sorting is used to choose the individuals to the next generation. The new algorithm is tested and compared with NSGA-II and RM-MEDA. The result shows that MMEA-RA outperforms RM-MEDA and NSGA-II on the test instances with variable linkages. At the same time, MMEA-RA has higher efficiency than the other two algorithms. A few shortcomings of MMEA-RA have also been identified and discussed in this paper.

  2. Syndrome identification based on 2D analysis software.

    Science.gov (United States)

    Boehringer, Stefan; Vollmar, Tobias; Tasse, Christiane; Wurtz, Rolf P; Gillessen-Kaesbach, Gabriele; Horsthemke, Bernhard; Wieczorek, Dagmar

    2006-10-01

    Clinical evaluation of children with developmental delay continues to present a challenge to the clinicians. In many cases, the face provides important information to diagnose a condition. However, database support with respect to facial traits is limited at present. Computer-based analyses of 2D and 3D representations of faces have been developed, but it is unclear how well a larger number of conditions can be handled by such systems. We have therefore analysed 2D pictures of patients each being affected with one of 10 syndromes (fragile X syndrome; Cornelia de Lange syndrome; Williams-Beuren syndrome; Prader-Willi syndrome; Mucopolysaccharidosis type III; Cri-du-chat syndrome; Smith-Lemli-Opitz syndrome; Sotos syndrome; Microdeletion 22q11.2; Noonan syndrome). We can show that a classification accuracy of >75% can be achieved for a computer-based diagnosis among the 10 syndromes, which is about the same accuracy achieved for five syndromes in a previous study. Pairwise discrimination of syndromes ranges from 80 to 99%. Furthermore, we can demonstrate that the criteria used by the computer decisions match clinical observations in many cases. These findings indicate that computer-based picture analysis might be a helpful addition to existing database systems, which are meant to assist in syndrome diagnosis, especially as data acquisition is straightforward and involves off-the-shelf digital camera equipment.

  3. Aerodynamic flight evaluation analysis and data base update

    Science.gov (United States)

    Boyle, W. W.; Miller, M. S.; Wilder, G. O.; Reheuser, R. D.; Sharp, R. S.; Bridges, G. I.

    1989-01-01

    Research was conducted to determine the feasibility of replacing the Solid Rocket Boosters on the existing Space Shuttle Launch Vehicle (SSLV) with Liquid Rocket Boosters (LRB). As a part of the LRB selection process, a series of wind tunnel tests were conducted along with aero studies to determine the effects of different LRB configurations on the SSLV. Final results were tabulated into increments and added to the existing SSLV data base. The research conducted in this study was taken from a series of wind tunnel tests conducted at Marshall's 14-inch Trisonic Wind Tunnel. The effects on the axial force (CAF), normal force (CNF), pitching moment (CMF), side force (CY), wing shear force (CSR), wing torque moment (CTR), and wing bending moment (CBR) coefficients were investigated for a number of candidate LRB configurations. The aero effects due to LRB protuberances, ET/LRB separation distance, and aft skirts were also gathered from the tests. Analysis was also conducted to investigate the base pressure and plume effects due to the new booster geometries. The test results found in Phases 1 and 2 of wind tunnel testing are discussed and compared. Preliminary LRB lateral/directional data results and trends are given. The protuberance and gap/skirt effects are discussed. The base pressure/plume effects study is discussed and results are given.

  4. A Research Roadmap for Computation-Based Human Reliability Analysis

    Energy Technology Data Exchange (ETDEWEB)

    Boring, Ronald [Idaho National Lab. (INL), Idaho Falls, ID (United States); Mandelli, Diego [Idaho National Lab. (INL), Idaho Falls, ID (United States); Joe, Jeffrey [Idaho National Lab. (INL), Idaho Falls, ID (United States); Smith, Curtis [Idaho National Lab. (INL), Idaho Falls, ID (United States); Groth, Katrina [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States)

    2015-08-01

    The United States (U.S.) Department of Energy (DOE) is sponsoring research through the Light Water Reactor Sustainability (LWRS) program to extend the life of the currently operating fleet of commercial nuclear power plants. The Risk Informed Safety Margin Characterization (RISMC) research pathway within LWRS looks at ways to maintain and improve the safety margins of these plants. The RISMC pathway includes significant developments in the area of thermalhydraulics code modeling and the development of tools to facilitate dynamic probabilistic risk assessment (PRA). PRA is primarily concerned with the risk of hardware systems at the plant; yet, hardware reliability is often secondary in overall risk significance to human errors that can trigger or compound undesirable events at the plant. This report highlights ongoing efforts to develop a computation-based approach to human reliability analysis (HRA). This computation-based approach differs from existing static and dynamic HRA approaches in that it: (i) interfaces with a dynamic computation engine that includes a full scope plant model, and (ii) interfaces with a PRA software toolset. The computation-based HRA approach presented in this report is called the Human Unimodels for Nuclear Technology to Enhance Reliability (HUNTER) and incorporates in a hybrid fashion elements of existing HRA methods to interface with new computational tools developed under the RISMC pathway. The goal of this research effort is to model human performance more accurately than existing approaches, thereby minimizing modeling uncertainty found in current plant risk models.

  5. Reliability Analysis of Aircraft Equipment Based on FMECA Method

    Science.gov (United States)

    Jun, Li; Huibin, Xu

    It is well known that reliability of aircraft equipment is very important to aircraft during the flight because performance of aircraft product can affect flight safe directly. In order to make the equipment work normally, FMECA is applied in an aircraft equipment to analyze its reliability and improve operational reliability of the product. Through its reliability mathematical model, average of operational time is predicted based on calculating failure probability of all electrical components. According to the process of reliability theory FMECA, all kinds of the failure mode, reasons, effects and criticality of the products can be determined completely. By comparing these criticality data as shown, the paper analyses adopted method by that the contents, accents and operating process of maintenance may be instituted finally. FMECA-based method for reliability analysis of the equipment and the equipment maintenance performs well. The results indicate that application of FMECA method can analyze reliability in detail and improve operational reliability of the equipment. Therefore this will supply theoretical bases and concrete measures of maintenance of the products to improve operational reliability of products. FMECA can be feasible and effective for improving operational reliability of all aircraft equipments.

  6. GPU-based Integration with Application in Sensitivity Analysis

    Science.gov (United States)

    Atanassov, Emanouil; Ivanovska, Sofiya; Karaivanova, Aneta; Slavov, Dimitar

    2010-05-01

    The presented work is an important part of the grid application MCSAES (Monte Carlo Sensitivity Analysis for Environmental Studies) which aim is to develop an efficient Grid implementation of a Monte Carlo based approach for sensitivity studies in the domains of Environmental modelling and Environmental security. The goal is to study the damaging effects that can be caused by high pollution levels (especially effects on human health), when the main modeling tool is the Danish Eulerian Model (DEM). Generally speaking, sensitivity analysis (SA) is the study of how the variation in the output of a mathematical model can be apportioned to, qualitatively or quantitatively, different sources of variation in the input of a model. One of the important classes of methods for Sensitivity Analysis are Monte Carlo based, first proposed by Sobol, and then developed by Saltelli and his group. In MCSAES the general Saltelli procedure has been adapted for SA of the Danish Eulerian model. In our case we consider as factors the constants determining the speeds of the chemical reactions in the DEM and as output a certain aggregated measure of the pollution. Sensitivity simulations lead to huge computational tasks (systems with up to 4 × 109 equations at every time-step, and the number of time-steps can be more than a million) which motivates its grid implementation. MCSAES grid implementation scheme includes two main tasks: (i) Grid implementation of the DEM, (ii) Grid implementation of the Monte Carlo integration. In this work we present our new developments in the integration part of the application. We have developed an algorithm for GPU-based generation of scrambled quasirandom sequences which can be combined with the CPU-based computations related to the SA. Owen first proposed scrambling of Sobol sequence through permutation in a manner that improves the convergence rates. Scrambling is necessary not only for error analysis but for parallel implementations. Good scrambling is

  7. Interpretation of motion analysis of laparoscopic instruments based on principal component analysis in box trainer settings.

    Science.gov (United States)

    Oropesa, Ignacio; Escamirosa, Fernando Pérez; Sánchez-Margallo, Juan A; Enciso, Silvia; Rodríguez-Vila, Borja; Martínez, Arturo Minor; Sánchez-Margallo, Francisco M; Gómez, Enrique J; Sánchez-González, Patricia

    2018-01-18

    Motion analysis parameters (MAPs) have been extensively validated for assessment of minimally invasive surgical skills. However, there are discrepancies on how specific MAPs, tasks, and skills match with each other, reflecting that motion analysis cannot be generalized independently of the learning outcomes of a task. Additionally, there is a lack of knowledge on the meaning of motion analysis in terms of surgical skills, making difficult the provision of meaningful, didactic feedback. In this study, new higher significance MAPs (HSMAPs) are proposed, validated, and discussed for the assessment of technical skills in box trainers, based on principal component analysis (PCA). Motion analysis data were collected from 25 volunteers performing three box trainer tasks (peg grasping/PG, pattern cutting/PC, knot suturing/KS) using the EVA tracking system. PCA was applied on 10 MAPs for each task and hand. Principal components were trimmed to those accounting for an explained variance > 80% to define the HSMAPs. Individual contributions of MAPs to HSMAPs were obtained by loading analysis and varimax rotation. Construct validity of the new HSMAPs was carried out at two levels of experience based on number of surgeries. Three new HSMAPs per hand were defined for PG and PC tasks, and two per hand for KS task. PG presented validity for HSMAPs related to insecurity and economy of space. PC showed validity for HSMAPs related to cutting efficacy, peripheral unawareness, and confidence. Finally, KS presented validity for HSMAPs related with economy of space and knotting security. PCA-defined HSMAPs can be used for technical skills' assessment. Construct validation and expert knowledge can be combined to infer how competences are acquired in box trainer tasks. These findings can be exploited to provide residents with meaningful feedback on performance. Future works will compare the new HSMAPs with valid scoring systems such as GOALS.

  8. Canonical correlation analysis for gene-based pleiotropy discovery.

    Directory of Open Access Journals (Sweden)

    Jose A Seoane

    2014-10-01

    Full Text Available Genome-wide association studies have identified a wealth of genetic variants involved in complex traits and multifactorial diseases. There is now considerable interest in testing variants for association with multiple phenotypes (pleiotropy and for testing multiple variants for association with a single phenotype (gene-based association tests. Such approaches can increase statistical power by combining evidence for association over multiple phenotypes or genetic variants respectively. Canonical Correlation Analysis (CCA measures the correlation between two sets of multidimensional variables, and thus offers the potential to combine these two approaches. To apply CCA, we must restrict the number of attributes relative to the number of samples. Hence we consider modules of genetic variation that can comprise a gene, a pathway or another biologically relevant grouping, and/or a set of phenotypes. In order to do this, we use an attribute selection strategy based on a binary genetic algorithm. Applied to a UK-based prospective cohort study of 4286 women (the British Women's Heart and Health Study, we find improved statistical power in the detection of previously reported genetic associations, and identify a number of novel pleiotropic associations between genetic variants and phenotypes. New discoveries include gene-based association of NSF with triglyceride levels and several genes (ACSM3, ERI2, IL18RAP, IL23RAP and NRG1 with left ventricular hypertrophy phenotypes. In multiple-phenotype analyses we find association of NRG1 with left ventricular hypertrophy phenotypes, fibrinogen and urea and pleiotropic relationships of F7 and F10 with Factor VII, Factor IX and cholesterol levels.

  9. Sensitivity Analysis of a process based erosion model using FAST

    Science.gov (United States)

    Gabelmann, Petra; Wienhöfer, Jan; Zehe, Erwin

    2015-04-01

    deposition are related to overland flow velocity using the equation of Engelund and Hansen and the sinking velocity of grain sizes, respectively. The sensitivity analysis was performed based on virtual hillslopes similar to those in the Weiherbach catchment. We applied the FAST-method (Fourier Amplitude Sensitivity Test), which provides a global sensitivity analysis with comparably few model runs. We varied model parameters in predefined and, for the Weiherbach catchment, physically meaningful parameter ranges. Those parameters included rainfall intensity, surface roughness, hillslope geometry, land use, erosion resistance, and soil hydraulic parameters. The results of this study allow guiding further modelling efforts in the Weiherbach catchment with respect to data collection and model modification.

  10. Institutional Analysis and Ecosystem-Based Management: The Institutional Analysis and Development Framework.

    Science.gov (United States)

    Imperial

    1999-11-01

    / Scholars, government practitioners, and environmentalists are increasingly supportive of collaborative, ecosystem-based approaches to natural resource management. However, few researchers have focused their attention on examining the important administrative and institutional challenges surrounding ecosystem-based management. This paper describes how the institutional analysis and development (IAD) framework can be used to better understand the institutional arrangements used to implement ecosystem-based management programs. Some of the observations emanating from previous research on institutional design and performance are also discussed. The paper's central argument is that if this new resource management paradigm is to take hold and flourish, researchers and practitioners must pay closer attention to the questions surrounding institutional design and performance. This should help improve our understanding of the relationship between science and human values in decision making. It should also help researchers avoid making faulty policy recommendations and improve the implementation of ecosystem-based management programs.KEY WORDS: Ecosystem management; Watershed management; Common pool resources; Implementation; Institutional analysis; Evaluation; Policy analysishttp://link.springer-ny.com/link/service/journals/00267/bibs/24n4p449.html

  11. Visual traffic jam analysis based on trajectory data.

    Science.gov (United States)

    Wang, Zuchao; Lu, Min; Yuan, Xiaoru; Zhang, Junping; van de Wetering, Huub

    2013-12-01

    In this work, we present an interactive system for visual analysis of urban traffic congestion based on GPS trajectories. For these trajectories we develop strategies to extract and derive traffic jam information. After cleaning the trajectories, they are matched to a road network. Subsequently, traffic speed on each road segment is computed and traffic jam events are automatically detected. Spatially and temporally related events are concatenated in, so-called, traffic jam propagation graphs. These graphs form a high-level description of a traffic jam and its propagation in time and space. Our system provides multiple views for visually exploring and analyzing the traffic condition of a large city as a whole, on the level of propagation graphs, and on road segment level. Case studies with 24 days of taxi GPS trajectories collected in Beijing demonstrate the effectiveness of our system.

  12. Analysis of valve failures from the NUCLARR data base

    International Nuclear Information System (INIS)

    Moore, L.M.

    1997-11-01

    The Nuclear Computerized Library for Assessing Reactor Reliability (NUCLARR) contains data on component failures with categorical and qualifying information such as component design, normal operating state, system application and safety grade information which is important to the development of risk-based component surveillance testing requirements. This report presents descriptions and results of analyses of valve component failure data and covariate information available in the document Nuclear Computerized Library for Assessing Reactor Reliability Data Manual, Part 3: Hardware Component Failure Data (NUCLARR Data Manual). Although there are substantial records on valve performance, there are many categories of the corresponding descriptors and qualifying information for which specific values are missing. Consequently, this limits the data available for analysis of covariate effects. This report presents cross tabulations by different covariate categories and limited modeling of covariate effects for data subsets with substantive non-missing covariate information

  13. Semantic analysis based forms information retrieval and classification

    Science.gov (United States)

    Saba, Tanzila; Alqahtani, Fatimah Ayidh

    2013-09-01

    Data entry forms are employed in all types of enterprises to collect hundreds of customer's information on daily basis. The information is filled manually by the customers. Hence, it is laborious and time consuming to use human operator to transfer these customers information into computers manually. Additionally, it is expensive and human errors might cause serious flaws. The automatic interpretation of scanned forms has facilitated many real applications from speed and accuracy point of view such as keywords spotting, sorting of postal addresses, script matching and writer identification. This research deals with different strategies to extract customer's information from these scanned forms, interpretation and classification. Accordingly, extracted information is segmented into characters for their classification and finally stored in the forms of records in databases for their further processing. This paper presents a detailed discussion of these semantic based analysis strategies for forms processing. Finally, new directions are also recommended for future research. [Figure not available: see fulltext.

  14. Chromatin Conformation Capture-Based Analysis of Nuclear Architecture.

    Science.gov (United States)

    Grob, Stefan; Grossniklaus, Ueli

    2017-01-01

    Nuclear organization and higher-order chromosome structure in interphase nuclei are thought to have important effects on fundamental biological processes, including chromosome condensation, replication, and transcription. Until recently, however, nuclear organization could only be analyzed microscopically. The development of chromatin conformation capture (3C)-based techniques now allows a detailed look at chromosomal architecture from the level of individual loci to the entire genome. Here we provide a robust Hi-C protocol, allowing the analysis of nuclear organization in nuclei from different wild-type and mutant plant tissues. This method is quantitative and provides a highly efficient and comprehensive way to study chromatin organization during plant development, in response to different environmental stimuli, and in mutants disrupting a variety of processes, including epigenetic pathways regulating gene expression.

  15. Web Pages Content Analysis Using Browser-Based Volunteer Computing

    Directory of Open Access Journals (Sweden)

    Wojciech Turek

    2013-01-01

    Full Text Available Existing solutions to the problem of finding valuable information on the Websuffers from several limitations like simplified query languages, out-of-date in-formation or arbitrary results sorting. In this paper a different approach to thisproblem is described. It is based on the idea of distributed processing of Webpages content. To provide sufficient performance, the idea of browser-basedvolunteer computing is utilized, which requires the implementation of text pro-cessing algorithms in JavaScript. In this paper the architecture of Web pagescontent analysis system is presented, details concerning the implementation ofthe system and the text processing algorithms are described and test resultsare provided.

  16. SILAC-based comparative analysis of pathogenic Escherichia coli secretomes

    DEFF Research Database (Denmark)

    Boysen, Anders; Borch, Jonas; Krogh, Thøger Jensen

    2015-01-01

    proteome analysis have the potential to discover both classes of proteins and hence form an important tool for discovering therapeutic targets. Adherent-invasive Escherichia coli (AIEC) and Enterotoxigenic E. coli (ETEC) are pathogenic variants of E. coli which cause intestinal disease in humans. AIEC......-term protection are still needed. In order to identify proteins with therapeutic potential, we have used mass spectrometry-based Stable Isotope Labeling with Amino acids in Cell culture (SILAC) quantitative proteomics method which allows us to compare the proteomes of pathogenic strains to commensal E. coli....... In this study, we grew the pathogenic strains ETEC H10407, AIEC LF82 and the non-pathogenic reference strain E. coli K-12 MG1655 in parallel and used SILAC to compare protein levels in OMVs and culture supernatant. We have identified well-known virulence factors from both AIEC and ETEC, thus validating our...

  17. Image Registration Algorithm Based on Parallax Constraint and Clustering Analysis

    Science.gov (United States)

    Wang, Zhe; Dong, Min; Mu, Xiaomin; Wang, Song

    2018-01-01

    To resolve the problem of slow computation speed and low matching accuracy in image registration, a new image registration algorithm based on parallax constraint and clustering analysis is proposed. Firstly, Harris corner detection algorithm is used to extract the feature points of two images. Secondly, use Normalized Cross Correlation (NCC) function to perform the approximate matching of feature points, and the initial feature pair is obtained. Then, according to the parallax constraint condition, the initial feature pair is preprocessed by K-means clustering algorithm, which is used to remove the feature point pairs with obvious errors in the approximate matching process. Finally, adopt Random Sample Consensus (RANSAC) algorithm to optimize the feature points to obtain the final feature point matching result, and the fast and accurate image registration is realized. The experimental results show that the image registration algorithm proposed in this paper can improve the accuracy of the image matching while ensuring the real-time performance of the algorithm.

  18. Multivariate analysis of eigenvalues and eigenvectors in tensor based morphometry

    Science.gov (United States)

    Rajagopalan, Vidya; Schwartzman, Armin; Hua, Xue; Leow, Alex; Thompson, Paul; Lepore, Natasha

    2015-01-01

    We develop a new algorithm to compute voxel-wise shape differences in tensor-based morphometry (TBM). As in standard TBM, we non-linearly register brain T1-weighed MRI data from a patient and control group to a template, and compute the Jacobian of the deformation fields. In standard TBM, the determinants of the Jacobian matrix at each voxel are statistically compared between the two groups. More recently, a multivariate extension of the statistical analysis involving the deformation tensors derived from the Jacobian matrices has been shown to improve statistical detection power.7 However, multivariate methods comprising large numbers of variables are computationally intensive and may be subject to noise. In addition, the anatomical interpretation of results is sometimes difficult. Here instead, we analyze the eigenvalues and the eigenvectors of the Jacobian matrices. Our method is validated on brain MRI data from Alzheimer's patients and healthy elderly controls from the Alzheimer's Disease Neuro Imaging Database.

  19. Architecture Analysis of an FPGA-Based Hopfield Neural Network

    Directory of Open Access Journals (Sweden)

    Miguel Angelo de Abreu de Sousa

    2014-01-01

    Full Text Available Interconnections between electronic circuits and neural computation have been a strongly researched topic in the machine learning field in order to approach several practical requirements, including decreasing training and operation times in high performance applications and reducing cost, size, and energy consumption for autonomous or embedded developments. Field programmable gate array (FPGA hardware shows some inherent features typically associated with neural networks, such as, parallel processing, modular executions, and dynamic adaptation, and works on different types of FPGA-based neural networks were presented in recent years. This paper aims to address different aspects of architectural characteristics analysis on a Hopfield Neural Network implemented in FPGA, such as maximum operating frequency and chip-area occupancy according to the network capacity. Also, the FPGA implementation methodology, which does not employ multipliers in the architecture developed for the Hopfield neural model, is presented, in detail.

  20. Component-based analysis of embedded control applications

    DEFF Research Database (Denmark)

    Angelov, Christo K.; Guan, Wei; Marian, Nicolae

    2011-01-01

    The widespread use of embedded systems requires the creation of industrial software technology that will make it possible to engineer systems being correct by construction. That can be achieved through the use of validated (trusted) components, verification of design models, and automatic...... instances of reusable, executable components—function blocks (FBs). System actors operate in accordance with a timed multitasking model of computation, whereby I/O signals are exchanged with the controlled plant at precisely specified time instants, resulting in the elimination of I/O jitter. The paper...... a feasible (light-weight) analysis method based on runtime observers. The latter are conceived as special-purpose actors running in parallel with the application actors, while checking system properties specified in Linear Temporal Logic. Observers are configured from reusable FBs that can be exported...