Systems Analysis for Interpretation of Phosphoproteomics Data

DEFF Research Database (Denmark)

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

2016-01-01

Global phosphoproteomics investigations yield overwhelming datasets with up to tens of thousands of quantified phosphosites. The main challenge after acquiring such large-scale data is to extract the biological meaning and relate this to the experimental question at hand. Systems level analysis...... 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...... provide a platform to generate functional protein networks and explore the relations between proteins of interest. The use of these tools requires careful consideration with regard to the input data, and the interpretation demands a critical approach. This chapter provides a summary of the most...

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......-scale phosphoproteome analysis alongside collisional induced dissociation, (CID) and electron capture/transfer dissociation (ECD/ETD)....

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

Phosphoproteomics Analysis of Endometrium in Women with or without Endometriosis

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Hong-Mei Xu

2015-01-01

Conclusions: That large-scale phosphoproteome quantification has been successfully identified in endometrium tissues of women with or without endometriosis will provide new insights to understand the molecular mechanisms of the development of endometriosis.

Quantitative phosphoproteomic analysis of porcine muscle within 24 h postmortem.

Science.gov (United States)

Huang, Honggang; Larsen, Martin R; Palmisano, Giuseppe; Dai, Jie; Lametsch, René

2014-06-25

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 phosphorylation levels in muscle within 24 h PM. The high phosphorylation level of heat shock proteins (HSPs) in early PM may be an adaptive response to slaughter stress and protect muscle cell from apoptosis, as observed in the serine 84 of HSP27. This work indicated that PM muscle proteins underwent significant changes at the phosphorylation level but were relatively stable at the total protein level, suggesting that protein phosphorylation may have important roles in meat quality development through the regulation of proteins involved in glucose metabolism and muscle contraction, thereby affecting glycolysis and rigor mortis development in PM muscle. The manuscript describes the characterization of postmortem (PM) porcine muscle within 24 h postmortem from the perspective of protein phosphorylation using advanced phosphoproteomic techniques. In the study, the authors employed the dimethyl labeling combined with the TiSH phosphopeptide enrichment and LC-MS/MS strategy. This was the first high-throughput quantitative phosphoproteomic study in PM muscle of farm animals. In the work, both the proteome

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.

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...

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

DEFF Research Database (Denmark)

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...... 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....... 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....

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

HIGHLIGHTS: Mass spectrometry (MS) based quantitative proteomics and phosphoproteomics applied to monitor the alteration of nuclear proteins during the early stages (4 hours) of preadipocyte differentiation. A total of 4072 proteins including 2434 phosphorylated proteins identified, a majority....... New insights into phosphorylation-dependent signaling networks that impact on nuclear proteins and controls adipocyte differentiation and cell fate. Adipocytes (fat cells) are important endocrine and metabolic cells critical for systemic insulin sensitivity. Both adipose excess and insufficiency......), in particular phosphorylation, play a major role in activating and propagating signals within TR networks upon induction of adipogenesis by extracellular stimulus. We applied mass spectrometry (MS) based quantitative proteomics and phosphoproteomics to monitor the alteration of nuclear proteins during the early...

Data set from a comprehensive phosphoproteomic analysis of rice variety IRBB5 in response to bacterial blight

Directory of Open Access Journals (Sweden)

Yuxuan Hou

2016-03-01

Full Text Available Bacterial blight (BB caused by Xanthomonas oryzae pv. oryzae (Xoo has become one of the most devastating diseases for rice, a major food source for over half of the world populations. To investigate the roles of protein phosphorylation in rice bacterial blight resistance, a quantitative phosphoproteomic study was conducted in rice variety IRBB5 at 0 h and 24 h after Xoo infection. 2367 and 2223 phosphosites on 1334 and 1297 representative proteins were identified in 0 h and 24 h after Xoo infection, respectively, out of which 762 proteins were found to be differentially phosphorylated. In associated with the published article “A comprehensive quantitative phosphoproteome analysis of rice in response to bacterial blight” in BMC Plant Biology (Hou et al., 2015 [1], this dataset article provided the detailed information of experimental designing, methods, features as well as the raw data of mass spectrometry (MS identification. The MS proteomics data could be fully accessed from the ProteomeXchange Consortium with the dataset identifier http://www.ebi.ac.uk/pride/archive/projects/PXD002222. Keywords: Rice (Oryza sativa L., Bacterial blight, Phosphoproteome

Improving the Phosphoproteome Coverage for Limited Sample Amounts Using TiOsub>2sub>-SIMAC-HILIC (TiSH) Phosphopeptide Enrichment and Fractionation

DEFF Research Database (Denmark)

Engholm-Keller, Kasper; Larsen, Martin R

2016-01-01

spectrometry (LC-MS/MS) analysis. Due to the sample loss resulting from fractionation, this procedure is mainly performed when large quantities of sample are available. To make large-scale phosphoproteomics applicable to smaller amounts of protein we have recently combined highly specific TiO2-based...... protocol we describe the procedure step by step to allow for comprehensive coverage of the phosphoproteome utilizing only a few hundred micrograms of protein....

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...

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...

Global dynamics of the Escherichia coli proteome and phosphoproteome during growth in minimal medium.

Science.gov (United States)

Soares, Nelson C; Spät, Philipp; Krug, Karsten; Macek, Boris

2013-06-07

Recent phosphoproteomics studies have generated relatively large data sets of bacterial proteins phosphorylated on serine, threonine, and tyrosine, implicating this type of phosphorylation in the regulation of vital processes of a bacterial cell; however, most phosphoproteomics studies in bacteria were so far qualitative. Here we applied stable isotope labeling by amino acids in cell culture (SILAC) to perform a quantitative analysis of proteome and phosphoproteome dynamics of Escherichia coli during five distinct phases of growth in the minimal medium. Combining two triple-SILAC experiments, we detected a total of 2118 proteins and quantified relative dynamics of 1984 proteins in all measured phases of growth, including 570 proteins associated with cell wall and membrane. In the phosphoproteomic experiment, we detected 150 Ser/Thr/Tyr phosphorylation events, of which 108 were localized to a specific amino acid residue and 76 were quantified in all phases of growth. Clustering analysis of SILAC ratios revealed distinct sets of coregulated proteins for each analyzed phase of growth and overrepresentation of membrane proteins in transition between exponential and stationary phases. The proteomics data indicated that proteins related to stress response typically associated with the stationary phase, including RpoS-dependent proteins, had increasing levels already during earlier phases of growth. Application of SILAC enabled us to measure median occupancies of phosphorylation sites, which were generally low (<12%). Interestingly, the phosphoproteome analysis showed a global increase of protein phosphorylation levels in the late stationary phase, pointing to a likely role of this modification in later phases of growth.

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

thousands of phosphorylation sites. However, in-depth phosphoproteomics often require off-line enrichment and fractionation techniques. In this study, we provide a detailed analysis of the physicochemical characteristics of phosphopeptides, which have been fractionated by off-line high-pH chromatography (Hp...... 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...

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...

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

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...... the reverse case. The phosphorylation level of 12 bands in sarcoplasmic fraction and 3 bands in myofibrillar fraction were significantly affected by the synergy effects of pH and time (p

Recent findings and technological advances in phosphoproteomics for cells and tissues

DEFF Research Database (Denmark)

von Stechow, Louise; Francavilla, Chiara; Olsen, Jesper V

2015-01-01

in different diseases, including cancer. Large-scale studies of phosphoproteins - termed phosphoproteomics - strongly rely on the use of high-performance mass spectrometric instrumentation. This powerful technology has been applied to study a great number of phosphorylation-based phenotypes. Nevertheless, many...... technical and biological challenges have to be overcome to identify biologically relevant phosphorylation sites in cells and tissues. This review describes different technological strategies to identify and quantify phosphorylation sites with high accuracy, without significant loss of analysis speed...

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

KAUST Repository

Rayapuram, Naganand; Bigeard, Jean; Alhoraibi, Hanna Mohsen Abdulrab; Bonhomme, Ludovic; Hesse, Anne-Marie; Vinh, Joelle; Hirt, Heribert; Pflieger, Delphine

2017-01-01

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.

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.

Enhanced Phosphoproteomic Profiling Workflow For Growth Factor Signaling Analysis

DEFF Research Database (Denmark)

Sylvester, Marc; Burbridge, Mike; Leclerc, Gregory

2010-01-01

Background Our understanding of complex signaling networks is still fragmentary. Isolated processes have been studied extensively but cross-talk is omnipresent and precludes intuitive predictions of signaling outcomes. The need for quantitative data on dynamic systems is apparent especially for our...... understanding of pathological processes. In our study we create and integrate data on phosphorylations that are initiated by several growth factor receptors. We present an approach for quantitative, time-resolved phosphoproteomic profiling that integrates the important contributions by phosphotyrosines. Methods...

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.

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

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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

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

DEFF Research Database (Denmark)

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

in β-cells by which this cytokine can modulate cell-matrix interactions during inflammation, a regulation shown in other cell types. Further data analysis is currently ongoing, and the collective results of the experiments will hopefully facilitate additional insights into the effect of IL-1β......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...

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...

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

DEFF Research Database (Denmark)

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...... of Biochemistry and Molecular Biology, University of Southern Denmark, Odense, Denmark 3Dept. of Oncology, Odense University Hospital, Odense, Denmark Cancer stem cells are thought to be responsible for tumorigenic potential and to possess resistance mechanisms against chemotherapy- and radiation-induced cancer...... cell death, while the bulk of a tumor lacks these capacities. The resistance mechanisms may cause these cells to survive and become the source of later tumor recurrence, highlighting the need for therapeutic strategies that specifically target pathways central to these cancer stem cells. The CD44hi...

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

DEFF Research Database (Denmark)

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

2011-01-01

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...... 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......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...

Construction of large signaling pathways using an adaptive perturbation approach with phosphoproteomic data.

Science.gov (United States)

Melas, Ioannis N; Mitsos, Alexander; Messinis, Dimitris E; Weiss, Thomas S; Rodriguez, Julio-Saez; Alexopoulos, Leonidas G

2012-04-01

Construction of large and cell-specific signaling pathways is essential to understand information processing under normal and pathological conditions. On this front, gene-based approaches offer the advantage of large pathway exploration whereas phosphoproteomic approaches offer a more reliable view of pathway activities but are applicable to small pathway sizes. In this paper, we demonstrate an experimentally adaptive approach to construct large signaling pathways from phosphoproteomic data within a 3-day time frame. Our approach--taking advantage of the fast turnaround time of the xMAP technology--is carried out in four steps: (i) screen optimal pathway inducers, (ii) select the responsive ones, (iii) combine them in a combinatorial fashion to construct a phosphoproteomic dataset, and (iv) optimize a reduced generic pathway via an Integer Linear Programming formulation. As a case study, we uncover novel players and their corresponding pathways in primary human hepatocytes by interrogating the signal transduction downstream of 81 receptors of interest and constructing a detailed model for the responsive part of the network comprising 177 species (of which 14 are measured) and 365 interactions.

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.

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.

Enrichment techniques employed in phosphoproteomics

Czech Academy of Sciences Publication Activity Database

Fíla, Jan; Honys, David

2012-01-01

Roč. 43, č. 3 (2012), s. 1025-1047 ISSN 0939-4451 R&D Projects: GA ČR(CZ) GAP501/11/1462; GA ČR GA522/09/0858; GA ČR GA525/09/0994; GA MŠk OC08011 Institutional research plan: CEZ:AV0Z50380511 Keywords : Phosphoproteomics * Enrichment * IMAC Subject RIV: ED - Physiology Impact factor: 3.914, year: 2012

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.

The proteome and phosphoproteome of maize pollen uncovers fertility candidate proteins.

Science.gov (United States)

Chao, Qing; Gao, Zhi-Fang; Wang, Yue-Feng; Li, Zhe; Huang, Xia-He; Wang, Ying-Chun; Mei, Ying-Chang; Zhao, Biligen-Gaowa; Li, Liang; Jiang, Yu-Bo; Wang, Bai-Chen

2016-06-01

Maize is unique since it is both monoecious and diclinous (separate male and female flowers on the same plant). We investigated the proteome and phosphoproteome of maize pollen containing modified proteins and here we provide a comprehensive pollen proteome and phosphoproteome which contain 100,990 peptides from 6750 proteins and 5292 phosphorylated sites corresponding to 2257 maize phosphoproteins, respectively. Interestingly, among the total 27 overrepresented phosphosite motifs we identified here, 11 were novel motifs, which suggested different modification mechanisms in plants compared to those of animals. Enrichment analysis of pollen phosphoproteins showed that pathways including DNA synthesis/chromatin structure, regulation of RNA transcription, protein modification, cell organization, signal transduction, cell cycle, vesicle transport, transport of ions and metabolisms, which were involved in pollen development, the following germination and pollen tube growth, were regulated by phosphorylation. In this study, we also found 430 kinases and 105 phosphatases in the maize pollen phosphoproteome, among which calcium dependent protein kinases (CDPKs), leucine rich repeat kinase, SNF1 related protein kinases and MAPK family proteins were heavily enriched and further analyzed. From our research, we also uncovered hundreds of male sterility-associated proteins and phosphoproteins that might influence maize productivity and serve as targets for hybrid maize seed production. At last, a putative complex signaling pathway involving CDPKs, MAPKs, ubiquitin ligases and multiple fertility proteins was constructed. Overall, our data provides new insight for further investigation of protein phosphorylation status in mature maize pollen and construction of maize male sterile mutants in the future.

Phosphoproteomics of Primary Cells Reveals Druggable Kinase Signatures in Ovarian Cancer

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Chiara Francavilla

2017-03-01

Full Text Available Our understanding of the molecular determinants of cancer is still inadequate because of cancer heterogeneity. Here, using epithelial ovarian cancer (EOC as a model system, we analyzed a minute amount of patient-derived epithelial cells from either healthy or cancerous tissues by single-shot mass-spectrometry-based phosphoproteomics. Using a multi-disciplinary approach, we demonstrated that primary cells recapitulate tissue complexity and represent a valuable source of differentially expressed proteins and phosphorylation sites that discriminate cancer from healthy cells. Furthermore, we uncovered kinase signatures associated with EOC. In particular, CDK7 targets were characterized in both EOC primary cells and ovarian cancer cell lines. We showed that CDK7 controls cell proliferation and that pharmacological inhibition of CDK7 selectively represses EOC cell proliferation. Our approach defines the molecular landscape of EOC, paving the way for efficient therapeutic approaches for patients. Finally, we highlight the potential of phosphoproteomics to identify clinically relevant and druggable pathways in cancer.

Phosphoproteomic biomarkers predicting histologic nonalcoholic steatohepatitis and fibrosis.

Science.gov (United States)

Younossi, Zobair M; Baranova, Ancha; Stepanova, Maria; Page, Sandra; Calvert, Valerie S; Afendy, Arian; Goodman, Zachary; Chandhoke, Vikas; Liotta, Lance; Petricoin, Emanuel

2010-06-04

The progression of nonalcoholic fatty liver disease (NAFLD) has been linked to deregulated exchange of the endocrine signaling between adipose and liver tissue. Proteomic assays for the phosphorylation events that characterize the activated or deactivated state of the kinase-driven signaling cascades in visceral adipose tissue (VAT) could shed light on the pathogenesis of nonalcoholic steatohepatitis (NASH) and related fibrosis. Reverse-phase protein microarrays (RPMA) were used to develop biomarkers for NASH and fibrosis using VAT collected from 167 NAFLD patients (training cohort, N = 117; testing cohort, N = 50). Three types of models were developed for NASH and advanced fibrosis: clinical models, proteomics models, and combination models. NASH was predicted by a model that included measurements of two components of the insulin signaling pathway: AKT kinase and insulin receptor substrate 1 (IRS1). The models for fibrosis were less reliable when predictions were based on phosphoproteomic, clinical, or the combination data. The best performing model relied on levels of the phosphorylation of GSK3 as well as on two subunits of cyclic AMP regulated protein kinase A (PKA). Phosphoproteomics technology could potentially be used to provide pathogenic information about NASH and NASH-related fibrosis. This information can lead to a clinically relevant diagnostic/prognostic biomarker for NASH.

Phosphoproteomic investigation of a solvent producing bacterium Clostridium acetobutylicum.

Science.gov (United States)

Bai, Xue; Ji, Zhihong

2012-07-01

In this study, we employed TiO₂ enrichment and high accuracy liquid chromatography-mass spectrometry-mass spectrometry to identify the phosphoproteome of Clostridium acetobutyicum ATCC824 in acidogenesis and solventogenesis. As many as 82 phosphopeptides in 61 proteins, with 107 phosphorylated sites on serine, threonine, or tyrosine, were identified with high confidence. We detected 52 phosphopeptides from 44 proteins in acidogenesis and 70 phosphopeptides from 51 proteins in solventogenesis, respectively. Bioinformatic analysis revealed most of the phosphoproteins located in cytoplasm and participated in carbon metabolism. Based on comparison between the two stages, we found 27 stage-specific phosphorylated proteins (10 in acidogenesis and 17 in solventogenesis), some of which were solvent production-related enzymes and metabolic regulators, showed significantly different phosphorylated status. Further analysis indicated that protein phosphorylation could be involved in the shift of stages or in solvent production pathway directly. Comparison against several other organisms revealed the evolutionary diversity among them on phosphorylation level in spite of their high homology on protein sequence level.

Phosphoproteome profiling for cold temperature perception.

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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.

Recent findings and technological advances in phosphoproteomics for cells and tissues.

Science.gov (United States)

von Stechow, Louise; Francavilla, Chiara; Olsen, Jesper V

2015-01-01

Site-specific phosphorylation is a fast and reversible covalent post-translational modification that is tightly regulated in cells. The cellular machinery of enzymes that write, erase and read these modifications (kinases, phosphatases and phospho-binding proteins) is frequently deregulated in different diseases, including cancer. Large-scale studies of phosphoproteins - termed phosphoproteomics - strongly rely on the use of high-performance mass spectrometric instrumentation. This powerful technology has been applied to study a great number of phosphorylation-based phenotypes. Nevertheless, many technical and biological challenges have to be overcome to identify biologically relevant phosphorylation sites in cells and tissues. This review describes different technological strategies to identify and quantify phosphorylation sites with high accuracy, without significant loss of analysis speed and reproducibility in tissues and cells. Moreover, computational tools for analysis, integration and biological interpretation of phosphorylation events are discussed.

Phosphoproteomics of Primary Cells Reveals Druggable Kinase Signatures in Ovarian Cancer.

Science.gov (United States)

Francavilla, Chiara; Lupia, Michela; Tsafou, Kalliopi; Villa, Alessandra; Kowalczyk, Katarzyna; Rakownikow Jersie-Christensen, Rosa; Bertalot, Giovanni; Confalonieri, Stefano; Brunak, Søren; Jensen, Lars J; Cavallaro, Ugo; Olsen, Jesper V

2017-03-28

Our understanding of the molecular determinants of cancer is still inadequate because of cancer heterogeneity. Here, using epithelial ovarian cancer (EOC) as a model system, we analyzed a minute amount of patient-derived epithelial cells from either healthy or cancerous tissues by single-shot mass-spectrometry-based phosphoproteomics. Using a multi-disciplinary approach, we demonstrated that primary cells recapitulate tissue complexity and represent a valuable source of differentially expressed proteins and phosphorylation sites that discriminate cancer from healthy cells. Furthermore, we uncovered kinase signatures associated with EOC. In particular, CDK7 targets were characterized in both EOC primary cells and ovarian cancer cell lines. We showed that CDK7 controls cell proliferation and that pharmacological inhibition of CDK7 selectively represses EOC cell proliferation. Our approach defines the molecular landscape of EOC, paving the way for efficient therapeutic approaches for patients. Finally, we highlight the potential of phosphoproteomics to identify clinically relevant and druggable pathways in cancer. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

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

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...... 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...

Characterization of early autophagy signaling by quantitative phosphoproteomics

DEFF Research Database (Denmark)

Rigbolt, Kristoffer Tg; Zarei, Mostafa; Sprenger, Adrian

2014-01-01

. To elucidate the regulation of early signaling events upon autophagy induction, we applied quantitative phosphoproteomics characterizing the temporal phosphorylation dynamics after starvation and rapamycin treatment. We obtained a comprehensive atlas of phosphorylation kinetics within the first 30 min upon...... revealing regulated phosphorylation sites on proteins involved in a wide range of cellular processes and an impact of the treatments on the kinome. To approach the potential function of the identified phosphorylation sites we performed a screen for MAP1LC3-interacting proteins and identified a group...... induction of autophagy with both treatments affecting widely different cellular processes. The identification of dynamic phosphorylation already after 2 min demonstrates that the earliest events in autophagy signaling occur rapidly after induction. The data was subjected to extensive bioinformatics analysis...

Activation of Human Peripheral Blood Eosinophils by Cytokines in a Comparative Time-Course Proteomic/Phosphoproteomic Study.

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Soman, Kizhake V; Stafford, Susan J; Pazdrak, Konrad; Wu, Zheng; Luo, Xuemei; White, Wendy I; Wiktorowicz, John E; Calhoun, William J; Kurosky, Alexander

2017-08-04

Activated eosinophils contribute to airway dysfunction and tissue remodeling in asthma and thus are considered to be important factors in asthma pathology. We report here comparative proteomic and phosphoproteomic changes upon activation of eosinophils using eight cytokines individually and in selected cytokine combinations in time-course reactions. Differential protein and phosphoprotein expressions were determined by mass spectrometry after 2-dimensional gel electrophoresis (2DGE) and by LC-MS/MS. We found that each cytokine-stimulation produced significantly different changes in the eosinophil proteome and phosphoproteome, with phosphoproteomic changes being more pronounced and having an earlier onset. Furthermore, we observed that IL-5, GM-CSF, and IL-3 showed the greatest change in protein expression and phosphorylation, and this expression differed markedly from those of the other five cytokines evaluated. Comprehensive univariate and multivariate statistical analyses were employed to evaluate the comparative results. We also monitored eosinophil activation using flow cytometry (FC) analysis of CD69. In agreement with our proteomic studies, FC indicated that IL-5, GM-CSF, and IL-3 were more effective than the other five cytokines studied in stimulating a cell surface CD69 increase indicative of eosinophil activation. Moreover, selected combinations of cytokines revealed proteomic patterns with many proteins in common with single cytokine expression patterns but also showed a greater effect of the two cytokines employed, indicating a more complex signaling pathway that was reflective of a more typical inflammatory pathology.

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

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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.

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

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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.

Quantitative phosphoproteomic analysis of caprine muscle with high and low meat quality.

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Liu, Manshun; Wei, Yanchao; Li, Xin; Quek, Siew Young; Zhao, Jing; Zhong, Huazhen; Zhang, Dequan; Liu, Yongfeng

2018-07-01

During the conversion of muscle to meat, protein phosphorylation can regulate various biological processes that have important effects on meat quality. To investigate the phosphorylation pattern of protein on rigor mortis, goat longissimus thoracis and external intercostals were classified into two groups (high quality and low quality), and meat quality was evaluated according to meat quality attributes (Warner-Bratzler shear force, Color, pH and drip loss). A quantitative mass spectrometry-based phosphoproteomic study was conducted to analyze the caprine muscle at 12h postmortem applying the TiO 2 -SIMAC-HILIC (TiSH) phosphopeptide enrichment strategy. A total of 2125 phosphopeptides were identified from 750 phosphoproteins. Among them, 96 proteins had differed in phosphorylation levels. The majority of these proteins are involved in glucose metabolism and muscle contraction. The differential phosphorylation level of proteins (PFK, MYL2 and HSP27) in two groups may be the crucial factors of regulating muscle rigor mortis. This study provides a comprehensive view for the phosphorylation status of caprine muscle at rigor mortis, it also gives a better understanding of the regulation of protein phosphorylation on various biological processes that affect the final meat quality attributes. Copyright © 2018. Published by Elsevier Ltd.

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....

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

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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 �

Quantitative phosphoproteomics reveals new roles for the protein phosphatase PP6 in mitotic cells.

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Rusin, Scott F; Schlosser, Kate A; Adamo, Mark E; Kettenbach, Arminja N

2015-10-13

Protein phosphorylation is an important regulatory mechanism controlling mitotic progression. Protein phosphatase 6 (PP6) is an essential enzyme with conserved roles in chromosome segregation and spindle assembly from yeast to humans. We applied a baculovirus-mediated gene silencing approach to deplete HeLa cells of the catalytic subunit of PP6 (PP6c) and analyzed changes in the phosphoproteome and proteome in mitotic cells by quantitative mass spectrometry-based proteomics. We identified 408 phosphopeptides on 272 proteins that increased and 298 phosphopeptides on 220 proteins that decreased in phosphorylation upon PP6c depletion in mitotic cells. Motif analysis of the phosphorylated sites combined with bioinformatics pathway analysis revealed previously unknown PP6c-dependent regulatory pathways. Biochemical assays demonstrated that PP6c opposed casein kinase 2-dependent phosphorylation of the condensin I subunit NCAP-G, and cellular analysis showed that depletion of PP6c resulted in defects in chromosome condensation and segregation in anaphase, consistent with dysregulation of condensin I function in the absence of PP6 activity. Copyright © 2015, American Association for the Advancement of Science.

Comparative Phosphoproteomic Analysis of the Developing Seeds in Two Indica Rice ( Oryza sativa L.) Cultivars with Different Starch Quality.

Science.gov (United States)

Pang, Yuehan; Zhou, Xin; Chen, Yaling; Bao, Jinsong

2018-03-21

Protein phosphorylation plays important roles in regulation of various molecular events such as plant growth and seed development. However, its involvement in starch biosynthesis is less understood. Here, a comparative phosphoproteomic analysis of two indica rice cultivars during grain development was performed. A total of 2079 and 2434 phosphopeptides from 1273 and 1442 phosphoproteins were identified, covering 2441 and 2808 phosphosites in indica rice 9311 and Guangluai4 (GLA4), respectively. Comparative analysis identified 303 differentially phosphorylated peptides, and 120 and 258 specifically phosphorylated peptides in 9311 and GLA4, respectively. Phosphopeptides in starch biosynthesis related enzymes such as AGPase, SSIIa, SSIIIa, BEI, BEIIb, PUL, and Pho1were identified. GLA4 and 9311 had different amylose content, pasting viscosities, and gelatinization temperature, suggesting subtle difference in starch biosynthesis and regulation between GLA4 and 9311. Our study will give added impetus to further understanding the regulatory mechanism of starch biosynthesis at the phosphorylation level.

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.

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

KAUST Repository

Bigeard, Jean; Rayapuram, Naganand; Bonhomme, Ludovic; Hirt, Heribert; Pflieger, Delphine

2014-01-01

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.

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.

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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.

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

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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.

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...

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

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

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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.

Comprehensive analysis of signal transduction in three-dimensional ECM-based tumor cell cultures

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Iris Eke

2015-11-01

Full Text Available Analysis of signal transduction and protein phosphorylation is fundamental to understand physiological and pathological cell behavior as well as identification of novel therapeutic targets. Despite the fact that more physiological three-dimensional cell culture assays are increasingly used, particularly proteomics and phosphoproteomics remain challenging due to easy, robust and reproducible sample preparation. Here, we present an easy-to-perform, reliable and time-efficient method for the production of 3D cell lysates without compromising cell adhesion before cell lysis. The samples can be used for Western blotting as well as phosphoproteome array technology. This technique would be of interest for researchers working in all fields of biology and drug development.

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

KAUST Repository

Joshi, Rubin N.; Binai, Nadine A.; Marabita, Francesco; Sui, Zhenhua; Altman, Amnon; Heck, Albert J. R.; Tegner, Jesper; Schmidt, Angelika

2017-01-01

(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

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

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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.

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.

Quantitative Phospho-proteomic Analysis of TNFα/NFκB Signaling Reveals a Role for RIPK1 Phosphorylation in Suppressing Necrotic Cell Death.

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Mohideen, Firaz; Paulo, Joao A; Ordureau, Alban; Gygi, Steve P; Harper, J Wade

2017-07-01

TNFα is a potent inducer of inflammation due to its ability to promote gene expression, in part via the NFκB pathway. Moreover, in some contexts, TNFα promotes Caspase-dependent apoptosis or RIPK1/RIPK3/MLKL-dependent necrosis. Engagement of the TNF Receptor Signaling Complex (TNF-RSC), which contains multiple kinase activities, promotes phosphorylation of several downstream components, including TAK1, IKKα/IKKβ, IκBα, and NFκB. However, immediate downstream phosphorylation events occurring in response to TNFα signaling are poorly understood at a proteome-wide level. Here we use Tandem Mass Tagging-based proteomics to quantitatively characterize acute TNFα-mediated alterations in the proteome and phosphoproteome with or without inhibition of the cIAP-dependent survival arm of the pathway with a SMAC mimetic. We identify and quantify over 8,000 phosphorylated peptides, among which are numerous known sites in the TNF-RSC, NFκB, and MAP kinase signaling systems, as well as numerous previously unrecognized phosphorylation events. Functional analysis of S320 phosphorylation in RIPK1 demonstrates a role for this event in suppressing its kinase activity, association with CASPASE-8 and FADD proteins, and subsequent necrotic cell death during inflammatory TNFα stimulation. This study provides a resource for further elucidation of TNFα-dependent signaling pathways. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Phosphoproteomics and new onco-bio technologies in the study of the pathogenesis and therapy of malignant gliomas

International Nuclear Information System (INIS)

De Maria, R.

2009-01-01

Characterization and crio-conservation and of glioblastoma stem cells. Phosphoproteomic analysis of tumor stem cells and their progeny. The possibility to use in research stem cells isolated from glioblastoma (GSCs) is an indispensable tool for the development of new and more effective therapeutic strategies for this type of cancer, whose prognosis is still poor. The research conducted for the attainment of the first objective has led to isolation of 18 stem cells lines from cancer patients with glioblastoma who have undergone surgery at the Institute of Neurosurgery of the Catholic University of Rome. The resulting cell lines were phenotypically characterized for the expression of stem cell markers and differentiation capabilities

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

DEFF Research Database (Denmark)

Batth, Tanveer S; Olsen, Jesper V

2016-01-01

Protein phosphorylation, a process in which kinases modify serines, threonines, and tyrosines with phosphoryl groups is of major importance in eukaryotic biology. Protein phosphorylation events are key initiators of signaling responses which determine cellular outcomes after environmental...... and metabolic stimuli, and are thus highly regulated. Therefore, studying the mechanism of regulation by phosphorylation, and pinpointing the exact site of phosphorylation on proteins is of high importance. This protocol describes in detail a phosphoproteomics workflow for ultra-deep coverage by fractionating...

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.

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

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

2010-02-05

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

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.

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

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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

Identification of Putative Mek1 Substrates during Meiosis in Saccharomyces cerevisiae Using Quantitative Phosphoproteomics.

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Raymond T Suhandynata

Full Text Available Meiotic recombination plays a key role in sexual reproduction as it generates crossovers that, in combination with sister chromatid cohesion, physically connect homologous chromosomes, thereby promoting their proper segregation at the first meiotic division. Meiotic recombination is initiated by programmed double strand breaks (DSBs catalyzed by the evolutionarily conserved, topoisomerase-like protein Spo11. Repair of these DSBs is highly regulated to create crossovers between homologs that are distributed throughout the genome. This repair requires the presence of the mitotic recombinase, Rad51, as well as the strand exchange activity of the meiosis-specific recombinase, Dmc1. A key regulator of meiotic DSB repair in Saccharomyces cerevisiae is the meiosis-specific kinase Mek1, which promotes interhomolog strand invasion and is required for the meiotic recombination checkpoint and the crossover/noncrossover decision. Understanding how Mek1 regulates meiotic recombination requires the identification of its substrates. Towards that end, an unbiased phosphoproteomic approach utilizing Stable Isotope Labeling by Amino Acids in Cells (SILAC was utilized to generate a list of potential Mek1 substrates, as well as proteins containing consensus phosphorylation sites for cyclin-dependent kinase, the checkpoint kinases, Mec1/Tel1, and the polo-like kinase, Cdc5. These experiments represent the first global phosphoproteomic dataset for proteins in meiotic budding yeast.

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

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Yang, Fen; Melo-Braga, Marcella N; Larsen, Martin R; Jørgensen, Hans J L; Palmisano, Giuseppe

2013-09-01

The fungus Septoria tritici causes the disease septoria tritici blotch in wheat, one of the most economically devastating foliar diseases in this crop. To investigate signaling events and defense responses in the wheat-S. tritici interaction, we performed a time-course study of S. tritici infection in resistant and susceptible wheat using quantitative proteomics and phosphoproteomics, with special emphasis on the initial biotrophic phase of interactions. Our study revealed an accumulation of defense and stress-related proteins, suppression of photosynthesis, and changes in sugar metabolism during compatible and incompatible interactions. However, differential regulation of the phosphorylation status of signaling proteins, transcription and translation regulators, and membrane-associated proteins was observed between two interactions. The proteomic data were correlated with a more rapid or stronger 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 in facilitating the initial symptomless growth. Taken in its entirety, our dataset suggests interplay between the plant and S. tritici through complex signaling networks and downstream molecular events. Resistance is likely related to several rapidly and intensively triggered signal transduction cascades resulting in a multiple-level activation of transcription and translation processes of defense responses. Our sensitive approaches and model provide a comprehensive

Quantitative phosphoproteome on the silkworm (Bombyx mori) cells infected with baculovirus.

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Shobahah, Jauharotus; Xue, Shengjie; Hu, Dongbing; Zhao, Cui; Wei, Ming; Quan, Yanping; Yu, Wei

2017-06-19

Bombyx mori has become an important model organism for many fundamental studies. Bombyx mori nucleopolyhedrovirus (BmNPV) is a significant pathogen to Bombyx mori, yet also an efficient vector for recombinant protein production. A previous study indicated that acetylation plays many vital roles in several cellular processes of Bombyx mori while global phosphorylation pattern upon BmNPV infection remains elusive. Employing tandem mass tag (TMT) labeling and phosphorylation affinity enrichment followed by high-resolution LC-MS/MS analysis and intensive bioinformatics analysis, the quantitative phosphoproteome in Bombyx mori cells infected by BmNPV at 24 hpi with an MOI of 10 was extensively examined. Totally, 6480 phosphorylation sites in 2112 protein groups were identified, among which 4764 sites in 1717 proteins were quantified. Among the quantified proteins, 81 up-regulated and 25 down-regulated sites were identified with significant criteria (the quantitative ratio above 1.3 was considered as up-regulation and below 0.77 was considered as down-regulation) and with significant p-value (p < 0.05). Some proteins of BmNPV were also hyperphosphorylated during infection, such as P6.9, 39 K, LEF-6, Ac58-like protein, Ac82-like protein and BRO-D. The phosphorylated proteins were primary involved in several specific functions, out of which, we focused on the binding activity, protein synthesis, viral replication and apoptosis through kinase activity.

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

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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.

Temporal dynamics of the Saccharopolyspora erythraea phosphoproteome.

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Licona-Cassani, Cuauhtemoc; Lim, Sooa; Marcellin, Esteban; Nielsen, Lars K

2014-05-01

Actinomycetes undergo a dramatic reorganization of metabolic and cellular machinery during a brief period of growth arrest ("metabolic switch") preceding mycelia differentiation and the onset of secondary metabolite biosynthesis. This study explores the role of phosphorylation in coordinating the metabolic switch in the industrial actinomycete Saccharopolyspora erythraea. A total of 109 phosphopeptides from 88 proteins were detected across a 150-h fermentation using open-profile two-dimensional LC-MS proteomics and TiO(2) enrichment. Quantitative analysis of the phosphopeptides and their unphosphorylated cognates was possible for 20 pairs that also displayed constant total protein expression. Enzymes from central carbon metabolism such as putative acetyl-coenzyme A carboxylase, isocitrate lyase, and 2-oxoglutarate dehydrogenase changed dramatically in the degree of phosphorylation during the stationary phase, suggesting metabolic rearrangement for the reutilization of substrates and the production of polyketide precursors. In addition, an enzyme involved in cellular response to environmental stress, trypsin-like serine protease (SACE_6340/NC_009142_6216), decreased in phosphorylation during the growth arrest stage. More important, enzymes related to the regulation of protein synthesis underwent rapid phosphorylation changes during this stage. Whereas the degree of phosphorylation of ribonuclease Rne/Rng (SACE_1406/NC_009142_1388) increased during the metabolic switch, that of two ribosomal proteins, S6 (SACE_7351/NC_009142_7233) and S32 (SACE_6101/NC_009142_5981), dramatically decreased during this stage of the fermentation, supporting the hypothesis that ribosome subpopulations differentially regulate translation before and after the metabolic switch. Overall, we show the great potential of phosphoproteomic studies to explain microbial physiology and specifically provide evidence of dynamic protein phosphorylation events across the developmental cycle of

Temporal Dynamics of the Saccharopolyspora erythraea Phosphoproteome*

Science.gov (United States)

Licona-Cassani, Cuauhtemoc; Lim, SooA; Marcellin, Esteban; Nielsen, Lars K.

2014-01-01

Actinomycetes undergo a dramatic reorganization of metabolic and cellular machinery during a brief period of growth arrest (“metabolic switch”) preceding mycelia differentiation and the onset of secondary metabolite biosynthesis. This study explores the role of phosphorylation in coordinating the metabolic switch in the industrial actinomycete Saccharopolyspora erythraea. A total of 109 phosphopeptides from 88 proteins were detected across a 150-h fermentation using open-profile two-dimensional LC-MS proteomics and TiO2 enrichment. Quantitative analysis of the phosphopeptides and their unphosphorylated cognates was possible for 20 pairs that also displayed constant total protein expression. Enzymes from central carbon metabolism such as putative acetyl-coenzyme A carboxylase, isocitrate lyase, and 2-oxoglutarate dehydrogenase changed dramatically in the degree of phosphorylation during the stationary phase, suggesting metabolic rearrangement for the reutilization of substrates and the production of polyketide precursors. In addition, an enzyme involved in cellular response to environmental stress, trypsin-like serine protease (SACE_6340/NC_009142_6216), decreased in phosphorylation during the growth arrest stage. More important, enzymes related to the regulation of protein synthesis underwent rapid phosphorylation changes during this stage. Whereas the degree of phosphorylation of ribonuclease Rne/Rng (SACE_1406/NC_009142_1388) increased during the metabolic switch, that of two ribosomal proteins, S6 (SACE_7351/NC_009142_7233) and S32 (SACE_6101/NC_009142_5981), dramatically decreased during this stage of the fermentation, supporting the hypothesis that ribosome subpopulations differentially regulate translation before and after the metabolic switch. Overall, we show the great potential of phosphoproteomic studies to explain microbial physiology and specifically provide evidence of dynamic protein phosphorylation events across the developmental cycle of

Quantitative proteome and phosphoproteome analyses of Streptomyces coelicolor reveal proteins and phosphoproteins modulating differentiation and secondary metabolism

DEFF Research Database (Denmark)

Rioseras, Beatriz; Sliaha, Pavel V; Gorshkov, Vladimir

2018-01-01

identified and quantified 3461 proteins corresponding to 44.3% of the S. coelicolor proteome across three developmental stages: vegetative hypha (MI); secondary metabolite producing hyphae (MII); and sporulating hyphae. A total of 1350 proteins exhibited more than 2-fold expression changes during....../Thr/Tyr kinases, making this genus an outstanding model for the study of bacterial protein phosphorylation events. We used mass spectrometry based quantitative proteomics and phosphoproteomics to characterize bacterial differentiation and activation of secondary metabolism of Streptomyces coelicolor. We...... the bacterial differentiation process. These proteins include 136 regulators (transcriptional regulators, transducers, Ser/Thr/Tyr kinases, signalling proteins), as well as 542 putative proteins with no clear homology to known proteins which are likely to play a role in differentiation and secondary metabolism...

Phosphoproteomics reveals that glycogen synthase kinase-3 phosphorylates multiple splicing factors and is associated with alternative splicing

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Shinde, Mansi Y.; Sidoli, Simone; Kulej, Katarzyna; Mallory, Michael J.; Radens, Caleb M.; Reicherter, Amanda L.; Myers, Rebecca L.; Barash, Yoseph; Lynch, Kristen W.; Garcia, Benjamin A.; Klein, Peter S.

2017-01-01

Glycogen synthase kinase-3 (GSK-3) is a constitutively active, ubiquitously expressed protein kinase that regulates multiple signaling pathways. In vitro kinase assays and genetic and pharmacological manipulations of GSK-3 have identified more than 100 putative GSK-3 substrates in diverse cell types. Many more have been predicted on the basis of a recurrent GSK-3 consensus motif ((pS/pT)XXX(S/T)), but this prediction has not been tested by analyzing the GSK-3 phosphoproteome. Using stable isotope labeling of amino acids in culture (SILAC) and MS techniques to analyze the repertoire of GSK-3–dependent phosphorylation in mouse embryonic stem cells (ESCs), we found that ∼2.4% of (pS/pT)XXX(S/T) sites are phosphorylated in a GSK-3–dependent manner. A comparison of WT and Gsk3a;Gsk3b knock-out (Gsk3 DKO) ESCs revealed prominent GSK-3–dependent phosphorylation of multiple splicing factors and regulators of RNA biosynthesis as well as proteins that regulate transcription, translation, and cell division. Gsk3 DKO reduced phosphorylation of the splicing factors RBM8A, SRSF9, and PSF as well as the nucleolar proteins NPM1 and PHF6, and recombinant GSK-3β phosphorylated these proteins in vitro. RNA-Seq of WT and Gsk3 DKO ESCs identified ∼190 genes that are alternatively spliced in a GSK-3–dependent manner, supporting a broad role for GSK-3 in regulating alternative splicing. The MS data also identified posttranscriptional regulation of protein abundance by GSK-3, with ∼47 proteins (1.4%) whose levels increased and ∼78 (2.4%) whose levels decreased in the absence of GSK-3. This study provides the first unbiased analysis of the GSK-3 phosphoproteome and strong evidence that GSK-3 broadly regulates alternative splicing. PMID:28916722

Phosphoproteome and Transcriptome of RA-Responsive and RA-Resistant Breast Cancer Cell Lines.

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Marilyn Carrier

Full Text Available Retinoic acid (RA, the main active vitamin A metabolite, controls multiple biological processes such as cell proliferation and differentiation through genomic programs and kinase cascades activation. Due to these properties, RA has proven anti-cancer capacity. Several breast cancer cells respond to the antiproliferative effects of RA, while others are RA-resistant. However, the overall signaling and transcriptional pathways that are altered in such cells have not been elucidated. Here, in a large-scale analysis of the phosphoproteins and in a genome-wide analysis of the RA-regulated genes, we compared two human breast cancer cell lines, a RA-responsive one, the MCF7 cell line, and a RA-resistant one, the BT474 cell line, which depicts several alterations of the "kinome". Using high-resolution nano-LC-LTQ-Orbitrap mass spectrometry associated to phosphopeptide enrichment, we found that several proteins involved in signaling and in transcription, are differentially phosphorylated before and after RA addition. The paradigm of these proteins is the RA receptor α (RARα, which was phosphorylated in MCF7 cells but not in BT474 cells after RA addition. The panel of the RA-regulated genes was also different. Overall our results indicate that RA resistance might correlate with the deregulation of the phosphoproteome with consequences on gene expression.

Phosphoproteomic insights into processes influenced by the kinase-like protein DIA1/C3orf58

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Agnieszka Hareza

2018-04-01

Full Text Available Many kinases are still ‘orphans,’ which means knowledge about their substrates, and often also about the processes they regulate, is lacking. Here, DIA1/C3orf58, a member of a novel predicted kinase-like family, is shown to be present in the endoplasmic reticulum and to influence trafficking via the secretory pathway. Subsequently, DIA1 is subjected to phosphoproteomics analysis to cast light on its signalling pathways. A liquid chromatography–tandem mass spectrometry proteomic approach with phosphopeptide enrichment is applied to membrane fractions of DIA1-overexpressing and control HEK293T cells, and phosphosites dependent on the presence of DIA1 are elucidated. Most of these phosphosites belonged to CK2- and proline-directed kinase types. In parallel, the proteomics of proteins immunoprecipitated with DIA1 reported its probable interactors. This pilot study provides the basis for deeper studies of DIA1 signalling.

Phosphoproteomic insights into processes influenced by the kinase-like protein DIA1/C3orf58.

Science.gov (United States)

Hareza, Agnieszka; Bakun, Magda; Świderska, Bianka; Dudkiewicz, Małgorzata; Koscielny, Alicja; Bajur, Anna; Jaworski, Jacek; Dadlez, Michał; Pawłowski, Krzysztof

2018-01-01

Many kinases are still 'orphans,' which means knowledge about their substrates, and often also about the processes they regulate, is lacking. Here, DIA1/C3orf58, a member of a novel predicted kinase-like family, is shown to be present in the endoplasmic reticulum and to influence trafficking via the secretory pathway. Subsequently, DIA1 is subjected to phosphoproteomics analysis to cast light on its signalling pathways. A liquid chromatography-tandem mass spectrometry proteomic approach with phosphopeptide enrichment is applied to membrane fractions of DIA1-overexpressing and control HEK293T cells, and phosphosites dependent on the presence of DIA1 are elucidated. Most of these phosphosites belonged to CK2- and proline-directed kinase types. In parallel, the proteomics of proteins immunoprecipitated with DIA1 reported its probable interactors. This pilot study provides the basis for deeper studies of DIA1 signalling.

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

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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.

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

Investigating temporal changes in the yeast phosphoproteome upon fatty acid starvation

DEFF Research Database (Denmark)

Pultz, Dennis; Bennetzen, Martin; Andersen, Jens S.

2011-01-01

under nutrition but not malnutrition extends the life span of multiple species, ranging from single-celled organisms like yeast to mammals. This increase in longevity by dietary restriction (DR) is coupled to profound beneficial effects on age-related pathology. Despite the number of studies on DR......Investigating stemporal changes in the yeast phosphoproteome upon fatty acid starvation Dennis Pultz*, Martin Bennetzen*, Jens S. Andersen and Nils J.Færgeman. Department of Biochemistry and Molecular Biology, University of Southern Denmark, Odense, Denmark, 5230 Reducing food intake to induce...... and the physiological changes DR induces, only little is known about the genetics and signalling networks which regulate the DR response. We have recently shown that inhibition of fatty acid synthesis in Saccharomyces cerevisiae results in a dependency on autophagy in maintaining normal life span. We further believe...

Quantitative phosphoproteomics reveals the role of protein arginine phosphorylation in the bacterial stress response.

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Schmidt, Andreas; Trentini, Débora Broch; Spiess, Silvia; Fuhrmann, Jakob; Ammerer, Gustav; Mechtler, Karl; Clausen, Tim

2014-02-01

Arginine phosphorylation is an emerging protein modification implicated in the general stress response of Gram-positive bacteria. The modification is mediated by the arginine kinase McsB, which phosphorylates and inactivates the heat shock repressor CtsR. In this study, we developed a mass spectrometric approach accounting for the peculiar chemical properties of phosphoarginine. The improved methodology was used to analyze the dynamic changes in the Bacillus subtilis arginine phosphoproteome in response to different stress situations. Quantitative analysis showed that a B. subtilis mutant lacking the YwlE arginine phosphatase accumulated a strikingly large number of arginine phosphorylations (217 sites in 134 proteins), however only a minor fraction of these sites was increasingly modified during heat shock or oxidative stress. The main targets of McsB-mediated arginine phosphorylation comprise central factors of the stress response system including the CtsR and HrcA heat shock repressors, as well as major components of the protein quality control system such as the ClpCP protease and the GroEL chaperonine. These findings highlight the impact of arginine phosphorylation in orchestrating the bacterial stress response.

Reactive Oxygen Species (ROS)-Activated ATM-Dependent Phosphorylation of Cytoplasmic Substrates Identified by Large-Scale Phosphoproteomics Screen*

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Kozlov, Sergei V.; Waardenberg, Ashley J.; Engholm-Keller, Kasper; Arthur, Jonathan W.; Graham, Mark E.; Lavin, Martin

2016-01-01

Ataxia-telangiectasia, mutated (ATM) protein plays a central role in phosphorylating a network of proteins in response to DNA damage. These proteins function in signaling pathways designed to maintain the stability of the genome and minimize the risk of disease by controlling cell cycle 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 ataxia-telangiectasia (A-T) 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, including 6,686 high-confidence sites mapping to 2,536 unique proteins. A total of 62 differentially phosphorylated peptides were identified; of these, 43 were phosphorylated in control but not in A-T cells, and 19 varied in their level of phosphorylation. Motif enrichment analysis of phosphopeptides revealed that consensus ATM serine glutamine sites were overrepresented. When considering phosphorylation events, only observed in control cells (not observed in A-T cells), with predicted ATM sites phosphoSerine/phosphoThreonine glutamine, we narrowed this list to 11 candidate ATM-dependent cytoplasmic proteins. Two of these 11 were previously described as ATM substrates (HMGA1 and UIMCI/RAP80), another five were identified in a whole cell extract phosphoproteomic screens, and the remaining four proteins had not been identified previously in DNA damage response screens. We validated the phosphorylation of three of these proteins (oxidative stress responsive 1 (OSR1), HDGF, and ccdc82) as ATM dependent after H2O2 exposure, and another protein (S100A11) demonstrated ATM

The phosphoproteome of Aspergillus nidulans reveals functional association with cellular processes involved in morphology and secretion.

Science.gov (United States)

Ramsubramaniam, Nikhil; Harris, Steven D; Marten, Mark R

2014-11-01

We describe the first phosphoproteome of the model filamentous fungus Aspergillus nidulans. Phosphopeptides were enriched using titanium dioxide, separated using a convenient ultra-long reverse phase gradient, and identified using a "high-high" strategy (high mass accuracy on the parent and fragment ions) with higher-energy collisional dissociation. Using this approach 1801 phosphosites, from 1637 unique phosphopeptides, were identified. Functional classification revealed phosphoproteins were overrepresented under GO categories related to fungal morphogenesis: "sites of polar growth," "vesicle mediated transport," and "cytoskeleton organization." In these same GO categories, kinase-substrate analysis of phosphoproteins revealed the majority were target substrates of CDK and CK2 kinase families, indicating these kinase families play a prominent role in fungal morphogenesis. Kinase-substrate analysis also identified 57 substrates for kinases known to regulate secretion of hydrolytic enzymes (e.g. PkaA, SchA, and An-Snf1). Altogether this data will serve as a benchmark that can be used to elucidate regulatory networks functionally associated with fungal morphogenesis and secretion. All MS data have been deposited in the ProteomeXchange with identifier PXD000715 (http://proteomecentral.proteomexchange.org/dataset/PXD000715). © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

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...

EBprot: Statistical analysis of labeling-based quantitative proteomics data.

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Koh, Hiromi W L; Swa, Hannah L F; Fermin, Damian; Ler, Siok Ghee; Gunaratne, Jayantha; Choi, Hyungwon

2015-08-01

Labeling-based proteomics is a powerful method for detection of differentially expressed proteins (DEPs). The current data analysis platform typically relies on protein-level ratios, which is obtained by summarizing peptide-level ratios for each protein. In shotgun proteomics, however, some proteins are quantified with more peptides than others, and this reproducibility information is not incorporated into the differential expression (DE) analysis. Here, we propose a novel probabilistic framework EBprot that directly models the peptide-protein hierarchy and rewards the proteins with reproducible evidence of DE over multiple peptides. To evaluate its performance with known DE states, we conducted a simulation study to show that the peptide-level analysis of EBprot provides better receiver-operating characteristic and more accurate estimation of the false discovery rates than the methods based on protein-level ratios. We also demonstrate superior classification performance of peptide-level EBprot analysis in a spike-in dataset. To illustrate the wide applicability of EBprot in different experimental designs, we applied EBprot to a dataset for lung cancer subtype analysis with biological replicates and another dataset for time course phosphoproteome analysis of EGF-stimulated HeLa cells with multiplexed labeling. Through these examples, we show that the peptide-level analysis of EBprot is a robust alternative to the existing statistical methods for the DE analysis of labeling-based quantitative datasets. The software suite is freely available on the Sourceforge website http://ebprot.sourceforge.net/. All MS data have been deposited in the ProteomeXchange with identifier PXD001426 (http://proteomecentral.proteomexchange.org/dataset/PXD001426/). © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

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.

Phosphoproteomics reveals the effect of ethylene in soybean root under flooding stress.

Science.gov (United States)

Yin, Xiaojian; Sakata, Katsumi; Komatsu, Setsuko

2014-12-05

Flooding has severe negative effects on soybean growth. To explore the flooding-responsive mechanisms in early-stage soybean, a phosphoproteomic approach was used. Two-day-old soybean plants were treated without or with flooding for 3, 6, 12, and 24 h, and root tip proteins were then extracted and analyzed at each time point. After 3 h of flooding exposure, the fresh weight of soybeans increased, whereas the ATP content of soybean root tips decreased. Using a gel-free proteomic technique, a total of 114 phosphoproteins were identified in the root tip samples, and 34 of the phosphoproteins were significantly changed with respect to phosphorylation status after 3 h of flooding stress. Among these phosphoproteins, eukaryotic translation initiation factors were dephosphorylated, whereas several protein synthesis-related proteins were phosphorylated. The mRNA expression levels of sucrose phosphate synthase 1F and eukaryotic translation initiation factor 4 G were down-regulated, whereas UDP-glucose 6-dehydrogenase mRNA expression was up-regulated during growth but down-regulated under flooding stress. Furthermore, bioinformatic protein interaction analysis of flooding-responsive proteins based on temporal phosphorylation patterns indicated that eukaryotic translation initiation factor 4 G was located in the center of the network during flooding. Soybean eukaryotic translation initiation factor 4 G has homology to programmed cell death 4 protein and is implicated in ethylene signaling. The weight of soybeans was increased with treatment by an ethylene-releasing agent under flooding condition, but it was decreased when plants were exposed to an ethylene receptor antagonist. These results suggest that the ethylene signaling pathway plays an important role, via the protein phosphorylation, in mechanisms of plant tolerance to the initial stages of flooding stress in soybean root tips.

Comparative Phosphoproteomics Reveals the Role of AmpC β-lactamase Phosphorylation in the Clinical Imipenem-resistant Strain Acinetobacter baumannii SK17*

Science.gov (United States)

Lai, Juo-Hsin; Yang, Jhih-Tian; Chern, Jeffy; Chen, Te-Li; Wu, Wan-Ling; Liao, Jiahn-Haur; Tsai, Shih-Feng; Liang, Suh-Yuen; Chou, Chi-Chi

2016-01-01

Nosocomial infectious outbreaks caused by multidrug-resistant Acinetobacter baumannii have emerged as a serious threat to human health. Phosphoproteomics of pathogenic bacteria has been used to identify the mechanisms of bacterial virulence and antimicrobial resistance. In this study, we used a shotgun strategy combined with high-accuracy mass spectrometry to analyze the phosphoproteomics of the imipenem-susceptible strain SK17-S and -resistant strain SK17-R. We identified 410 phosphosites on 248 unique phosphoproteins in SK17-S and 285 phosphosites on 211 unique phosphoproteins in SK17-R. The distributions of the Ser/Thr/Tyr/Asp/His phosphosites in SK17-S and SK17-R were 47.0%/27.6%/12.4%/8.0%/4.9% versus 41.4%/29.5%/17.5%/6.7%/4.9%, respectively. The Ser-90 phosphosite, located on the catalytic motif S88VS90K of the AmpC β-lactamase, was first identified in SK17-S. Based on site-directed mutagenesis, the nonphosphorylatable mutant S90A was found to be more resistant to imipenem, whereas the phosphorylation-simulated mutant S90D was sensitive to imipenem. Additionally, the S90A mutant protein exhibited higher β-lactamase activity and conferred greater bacterial protection against imipenem in SK17-S compared with the wild-type. In sum, our results revealed that in A. baumannii, Ser-90 phosphorylation of AmpC negatively regulates both β-lactamase activity and the ability to counteract the antibiotic effects of imipenem. These findings highlight the impact of phosphorylation-mediated regulation in antibiotic-resistant bacteria on future drug design and new therapies. PMID:26499836

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

Directory of Open Access Journals (Sweden)

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

The beginnings of crop phosphoproteomics: exploring early warning systems of stress.

Directory of Open Access Journals (Sweden)

Christof eRampitsch

2012-07-01

Full Text Available This review examines why a knowledge of plant protein phosphorylation events is important in devising strategies to protect crops from both biotic and abiotic stresses, and why proteomics should be included when studying stress pathways. Most of the achievements in elucidating phospho-signalling pathways in biotic and abiotic stress are reported from model systems: while these are discussed, this review attempts mainly to focus on work done with crops, with examples of achievements reported from rice, maize, wheat, grape, Brassica, tomato and soy bean after cold acclimation, hormonal and oxidative H2O2 treatment, salt stress, mechanical wounding or pathogen challenge. The challenges that remain to transfer this information into a format that can be used to protect crops against biotic and abiotic stresses are enormous. The tremendous increase in the speed and ease of DNA sequencing is poised to reveal the whole genomes of many crop species in the near future, which will facilitate phosphoproteomics and phosphogenomics research.

Phosphoproteomic Analysis Reveals a Novel Mechanism of CaMKIIα Regulation Inversely Induced by Cocaine Memory Extinction versus Reconsolidation

Science.gov (United States)

Rich, Matthew T.; Abbott, Thomas B.; Chung, Lisa; Gulcicek, Erol E.; Stone, Kathryn L.; Colangelo, Christopher M.; Lam, TuKiet T.; Nairn, Angus C.; Taylor, Jane R.

2016-01-01

Successful addiction treatment depends on maintaining long-term abstinence, making relapse prevention an essential therapeutic goal. However, exposure to environmental cues associated with drug use often thwarts abstinence efforts by triggering drug using memories that drive craving and relapse. We sought to develop a dual approach for weakening cocaine memories through phosphoproteomic identification of targets regulated in opposite directions by memory extinction compared with reconsolidation in male Sprague-Dawley rats that had been trained to self-administer cocaine paired with an audiovisual cue. We discovered a novel, inversely regulated, memory-dependent phosphorylation event on calcium-calmodulin-dependent kinase II α (CaMKIIα) at serine (S)331. Correspondingly, extinction-associated S331 phosphorylation inhibited CaMKIIα activity. Intra-basolateral amygdala inhibition of CaMKII promoted memory extinction and disrupted reconsolidation, leading to a reduction in subsequent cue-induced reinstatement. CaMKII inhibition had no effect if the memory was neither retrieved nor extinguished. Therefore, inhibition of CaMKII represents a novel mechanism for memory-based addiction treatment that leverages both extinction enhancement and reconsolidation disruption to reduce relapse-like behavior. SIGNIFICANCE STATEMENT Preventing relapse to drug use is an important goal for the successful treatment of addictive disorders. Relapse-prevention therapies attempt to interfere with drug-associated memories, but are often hindered by unintentional memory strengthening. In this study, we identify phosphorylation events that are bidirectionally regulated by the reconsolidation versus extinction of a cocaine-associated memory, including a novel site on CaMKIIα. Additionally, using a rodent model of addiction, we show that CaMKII inhibition in the amygdala can reduce relapse-like behavior. Together, our data supports the existence of mechanisms that can be used to enhance

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.

Comparative N-glycoproteomic and phosphoproteomic profiling of human placental plasma membrane between normal and preeclampsia pregnancies with high-resolution mass spectrometry.

Directory of Open Access Journals (Sweden)

Fuqiang Wang

Full Text Available Preeclampsia is a serious complication of pregnancy, which affects 2-8% of all pregnancies and is one of the leading causes of maternal and perinatal mortality and morbidity worldwide. To better understand the molecular mechanisms involved in pathological development of placenta in preeclampsia, we used high-resolution LC-MS/MS technologies to construct a comparative N-glycoproteomic and phosphoproteomic profiling of human placental plasma membrane in normal and preeclamptic pregnancies. A total of 1027 N-glyco- and 2094 phospho- sites were detected in human placental plasma membrane, and 5 N-glyco- and 38 phospho- proteins, respectively, with differentially expression were definitively identified between control and preeclamptic placental plasma membrane. Further bioinformatics analysis indicated that these differentially expressed proteins correlate with several specific cellular processes occurring during pathological changes of preeclamptic placental plasma membrane.

Comparative Phosphoproteomics Reveals the Role of AmpC β-lactamase Phosphorylation in the Clinical Imipenem-resistant Strain Acinetobacter baumannii SK17.

Science.gov (United States)

Lai, Juo-Hsin; Yang, Jhih-Tian; Chern, Jeffy; Chen, Te-Li; Wu, Wan-Ling; Liao, Jiahn-Haur; Tsai, Shih-Feng; Liang, Suh-Yuen; Chou, Chi-Chi; Wu, Shih-Hsiung

2016-01-01

Nosocomial infectious outbreaks caused by multidrug-resistant Acinetobacter baumannii have emerged as a serious threat to human health. Phosphoproteomics of pathogenic bacteria has been used to identify the mechanisms of bacterial virulence and antimicrobial resistance. In this study, we used a shotgun strategy combined with high-accuracy mass spectrometry to analyze the phosphoproteomics of the imipenem-susceptible strain SK17-S and -resistant strain SK17-R. We identified 410 phosphosites on 248 unique phosphoproteins in SK17-S and 285 phosphosites on 211 unique phosphoproteins in SK17-R. The distributions of the Ser/Thr/Tyr/Asp/His phosphosites in SK17-S and SK17-R were 47.0%/27.6%/12.4%/8.0%/4.9% versus 41.4%/29.5%/17.5%/6.7%/4.9%, respectively. The Ser-90 phosphosite, located on the catalytic motif S(88)VS(90)K of the AmpC β-lactamase, was first identified in SK17-S. Based on site-directed mutagenesis, the nonphosphorylatable mutant S90A was found to be more resistant to imipenem, whereas the phosphorylation-simulated mutant S90D was sensitive to imipenem. Additionally, the S90A mutant protein exhibited higher β-lactamase activity and conferred greater bacterial protection against imipenem in SK17-S compared with the wild-type. In sum, our results revealed that in A. baumannii, Ser-90 phosphorylation of AmpC negatively regulates both β-lactamase activity and the ability to counteract the antibiotic effects of imipenem. These findings highlight the impact of phosphorylation-mediated regulation in antibiotic-resistant bacteria on future drug design and new therapies. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Phosphoproteome profiles of the phytopathogenic fungi Alternaria brassicicola and Botrytis cinerea during exponential growth in axenic cultures.

Science.gov (United States)

Davanture, Marlène; Dumur, Jérôme; Bataillé-Simoneau, Nelly; Campion, Claire; Valot, Benoît; Zivy, Michel; Simoneau, Philippe; Fillinger, Sabine

2014-07-01

This study describes the gel-free phosphoproteomic analysis of the phytopathogenic fungi Alternaria brassicicola and Botrytis cinerea grown in vitro under nonlimiting conditions. Using a combination of strong cation exchange and IMAC prior to LC-MS, we identified over 1350 phosphopeptides per fungus representing over 800 phosphoproteins. The preferred phosphorylation sites were found on serine (>80%) and threonine (>15%), whereas phosphorylated tyrosine residues were found at less than 1% in A. brassicicola and at a slightly higher ratio in B. cinerea (1.5%). Biological processes represented principally among the phoshoproteins were those involved in response and transduction of stimuli as well as in regulation of cellular and metabolic processes. Most known elements of signal transduction were found in the datasets of both fungi. This study also revealed unexpected phosphorylation sites in histidine kinases, a category overrepresented in filamentous ascomycetes compared to yeast. The data have been deposited to the ProteomeXchange database with identifier PXD000817 (http://proteomecentral.proteomexchange.org/dataset/PXD000817). © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

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.

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; Akimov, Vyacheslav

2011-01-01

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...... of the matching sequence motif. In addition to identifying previously unknown phosphorylation sites on factors associated with differentiation, such as kinases and transcription factors, we observed dynamic phosphorylation of DNA methyltransferases (DNMTs). We found a specific interaction of DNMTs during early......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...

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

The fungus Septoria tritici causes the disease septoria tritici blotch in wheat, one of the most economically devastating foliar diseases in this crop. To investigate signaling events and defense responses in the wheat-S. tritici interaction, we performed a time-course study of S. tritici infection...... in resistant and susceptible wheat using quantitative proteomics and phosphoproteomics, with special emphasis on the initial biotrophic phase of interactions. Our study revealed an accumulation of defense and stress-related proteins, suppression of photosynthesis, and changes in sugar metabolism during...... compatible and incompatible interactions. However, differential regulation of the phosphorylation status of signaling proteins, transcription and translation regulators, and membrane-associated proteins was observed between two interactions. The proteomic data were correlated with a more rapid or stronger...

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

Science.gov (United States)

Rodrigues, Rafael Torres de Souza; Chizzotti, Mario Luiz; Vital, Camilo Elber; Baracat-Pereira, Maria Cristina; Barros, Edvaldo; Busato, Karina Costa; Gomes, Rafael Aparecido; Ladeira, Márcio Machado; Martins, Taiane da Silva

2017-01-01

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 (PAngus had greater phosphorylation of phosphoglucomutase-1 and troponin-T (PAngus 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 contraction force, susceptibility to calpain, apoptosis and postmortem glycolysis, which might also be related to differences in beef quality among Angus and Nellore.

An Augmented Multiple-Protease-Based Human Phosphopeptide Atlas

NARCIS (Netherlands)

Giansanti, Piero; Aye, Thin Thin; van den Toorn, Henk; Peng, Mao; van Breukelen, Bas; Heck, Albert J R

2015-01-01

Although mass-spectrometry-based screens enable thousands of protein phosphorylation sites to be monitored simultaneously, they often do not cover important regulatory sites. Here, we hypothesized that this is due to the fact that nearly all large-scale phosphoproteome studies are initiated by

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.

Comparative gel-based phosphoproteomics in response to signaling molecules

KAUST Repository

Marondedze, Claudius; Lilley, Kathryn S.; Thomas, Ludivine

2013-01-01

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.

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.

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

ATM (ataxia-telangiectasia, mutated) protein plays a central role in phosphorylating a network of proteins in response to DNA damage. These proteins function in signalling pathways designed to maintain the stability of the genome and minimize the risk of disease by controlling cell cycle checkpoi......ATM (ataxia-telangiectasia, mutated) protein plays a central role in phosphorylating a network of proteins in response to DNA damage. These proteins function in signalling pathways designed to maintain the stability of the genome and minimize the risk of disease by controlling cell cycle...... 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...

A Library of Phosphoproteomic and Chromatin Signatures for Characterizing Cellular Responses to Drug Perturbations.

Science.gov (United States)

Litichevskiy, Lev; Peckner, Ryan; Abelin, Jennifer G; Asiedu, Jacob K; Creech, Amanda L; Davis, John F; Davison, Desiree; Dunning, Caitlin M; Egertson, Jarrett D; Egri, Shawn; Gould, Joshua; Ko, Tak; Johnson, Sarah A; Lahr, David L; Lam, Daniel; Liu, Zihan; Lyons, Nicholas J; Lu, Xiaodong; MacLean, Brendan X; Mungenast, Alison E; Officer, Adam; Natoli, Ted E; Papanastasiou, Malvina; Patel, Jinal; Sharma, Vagisha; Toder, Courtney; Tubelli, Andrew A; Young, Jennie Z; Carr, Steven A; Golub, Todd R; Subramanian, Aravind; MacCoss, Michael J; Tsai, Li-Huei; Jaffe, Jacob D

2018-04-25

Although the value of proteomics has been demonstrated, cost and scale are typically prohibitive, and gene expression profiling remains dominant for characterizing cellular responses to perturbations. However, high-throughput sentinel assays provide an opportunity for proteomics to contribute at a meaningful scale. We present a systematic library resource (90 drugs × 6 cell lines) of proteomic signatures that measure changes in the reduced-representation phosphoproteome (P100) and changes in epigenetic marks on histones (GCP). A majority of these drugs elicited reproducible signatures, but notable cell line- and assay-specific differences were observed. Using the "connectivity" framework, we compared signatures across cell types and integrated data across assays, including a transcriptional assay (L1000). Consistent connectivity among cell types revealed cellular responses that transcended lineage, and consistent connectivity among assays revealed unexpected associations between drugs. We further leveraged the resource against public data to formulate hypotheses for treatment of multiple myeloma and acute lymphocytic leukemia. This resource is publicly available at https://clue.io/proteomics. Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

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.

Network analysis of cancer PSB 2014 Poster

OpenAIRE

McDermott, Jason

2014-01-01

Cancer is, in general, a complex disease; it operates on pathways and systems, not solely on the individual components of those systems (genes or proteins). We have gathered global proteomic and phosphoproteomic data from a set of tumors with existing genomic data (sequencing, methylation, miRNA and mRNA expression) associated with a range of survival phenotypes. We report on our recent progress in analyzing proteomic, phosphoproteomic, and accompanying genomic data in terms of pathways that ...

Integrative analysis of kinase networks in TRAIL-induced apoptosis provides a source of potential targets for combination therapy

DEFF Research Database (Denmark)

So, Jonathan; Pasculescu, Adrian; Dai, Anna Y.

2015-01-01

phosphoproteomics. With these protein interaction maps, we modeled information flow through the networks and identified apoptosis-modifying kinases that are highly connected to regulated substrates downstream of TRAIL. The results of this analysis provide a resource of potential targets for the development of TRAIL...

Dynamic Interaction- and Phospho-Proteomics Reveal Lck as a Major Signaling Hub of CD147 in T Cells.

Science.gov (United States)

Supper, Verena; Hartl, Ingrid; Boulègue, Cyril; Ohradanova-Repic, Anna; Stockinger, Hannes

2017-03-15

Numerous publications have addressed CD147 as a tumor marker and regulator of cytoskeleton, cell growth, stress response, or immune cell function; however, the molecular functionality of CD147 remains incompletely understood. Using affinity purification, mass spectrometry, and phosphopeptide enrichment of isotope-labeled peptides, we examined the dynamic of the CD147 microenvironment and the CD147-dependent phosphoproteome in the Jurkat T cell line upon treatment with T cell stimulating agents. We identified novel dynamic interaction partners of CD147 such as CD45, CD47, GNAI2, Lck, RAP1B, and VAT1 and, furthermore, found 76 CD147-dependent phosphorylation sites on 57 proteins. Using the STRING protein network database, a network between the CD147 microenvironment and the CD147-dependent phosphoproteins was generated and led to the identification of key signaling hubs around the G proteins RAP1B and GNB1, the kinases PKCβ, PAK2, Lck, and CDK1, and the chaperone HSPA5. Gene ontology biological process term analysis revealed that wound healing-, cytoskeleton-, immune system-, stress response-, phosphorylation- and protein modification-, defense response to virus-, and TNF production-associated terms are enriched within the microenvironment and the phosphoproteins of CD147. With the generated signaling network and gene ontology biological process term grouping, we identify potential signaling routes of CD147 affecting T cell growth and function. Copyright © 2017 by The American Association of Immunologists, Inc.

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.

SILAC-based quantification of changes in protein tyrosine phosphorylation induced by Interleukin-2 (IL-2) and IL-15 in T-lymphocytes

DEFF Research Database (Denmark)

Osinalde, Nerea; Sánchez-Quiles, Virginia; Akimov, Vyacheslav

2015-01-01

This data article presents the first large-scale quantitative phosphoproteomics dataset generated to decipher the signaling networks initiated by IL-2 and IL-15 in T-lymphocytes. Data was collected by combining immunoprecipitation of tyrosine phosphorylated proteins and TiO2-based phosphopeptide...

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.

Hippocampal phosphoproteomics of F344 rats exposed to 1-bromopropane

International Nuclear Information System (INIS)

Huang, Zhenlie; Ichihara, Sahoko; Oikawa, Shinji; Chang, Jie; Zhang, Lingyi; Hu, Shijie; Huang, Hanlin; Ichihara, Gaku

2015-01-01

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 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 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 of GRP78

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

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.

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.

Deciphering Phosphotyrosine-Dependent Signaling Networks in Cancer by SH2 Profiling

Science.gov (United States)

Machida, Kazuya; Khenkhar, Malik

2012-01-01

It has been a decade since the introduction of SH2 profiling, a modular domain-based molecular diagnostics tool. This review covers the original concept of SH2 profiling, different analytical platforms, and their applications, from the detailed analysis of single proteins to broad screening in translational research. Illustrated by practical examples, we discuss the uniqueness and advantages of the approach as well as its limitations and challenges. We provide guidance for basic researchers and oncologists who may consider SH2 profiling in their respective cancer research, especially for those focusing on tyrosine phosphoproteomics. SH2 profiling can serve as an alternative phosphoproteomics tool to dissect aberrant tyrosine kinase pathways responsible for individual malignancies, with the goal of facilitating personalized diagnostics for the treatment of cancer. PMID:23226573

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

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.

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.

Highly Efficient Single-Step Enrichment of Low Abundance Phosphopeptides from Plant Membrane Preparations

Directory of Open Access Journals (Sweden)

Xu Na Wu

2017-09-01

Full Text Available Mass spectrometry (MS-based large scale phosphoproteomics has facilitated the investigation of plant phosphorylation dynamics on a system-wide scale. However, generating large scale data sets for membrane phosphoproteins usually requires fractionation of samples and extended hands-on laboratory time. To overcome these limitations, we developed “ShortPhos,” an efficient and simple phosphoproteomics protocol optimized for research on plant membrane proteins. The optimized workflow allows fast and efficient identification and quantification of phosphopeptides, even from small amounts of starting plant materials. “ShortPhos” can produce label-free datasets with a high quantitative reproducibility. In addition, the “ShortPhos” protocol recovered more phosphorylation sites from membrane proteins, especially plasma membrane and vacuolar proteins, when compared to our previous workflow and other membrane-based data in the PhosPhAt 4.0 database. We applied “ShortPhos” to study kinase-substrate relationships within a nitrate-induction experiment on Arabidopsis roots. The “ShortPhos” identified significantly more known kinase-substrate relationships compared to previous phosphoproteomics workflows, producing new insights into nitrate-induced signaling pathways.

Quantitative Phosphoproteomics Reveals Wee1 Kinase as a Therapeutic Target in a Model of Proneural Glioblastoma.

Science.gov (United States)

Lescarbeau, Rebecca S; Lei, Liang; Bakken, Katrina K; Sims, Peter A; Sarkaria, Jann N; Canoll, Peter; White, Forest M

2016-06-01

Glioblastoma (GBM) is the most common malignant primary brain cancer. With a median survival of about a year, new approaches to treating this disease are necessary. To identify signaling molecules regulating GBM progression in a genetically engineered murine model of proneural GBM, we quantified phosphotyrosine-mediated signaling using mass spectrometry. Oncogenic signals, including phosphorylated ERK MAPK, PI3K, and PDGFR, were found to be increased in the murine tumors relative to brain. Phosphorylation of CDK1 pY15, associated with the G2 arrest checkpoint, was identified as the most differentially phosphorylated site, with a 14-fold increase in phosphorylation in the tumors. To assess the role of this checkpoint as a potential therapeutic target, syngeneic primary cell lines derived from these tumors were treated with MK-1775, an inhibitor of Wee1, the kinase responsible for CDK1 Y15 phosphorylation. MK-1775 treatment led to mitotic catastrophe, as defined by increased DNA damage and cell death by apoptosis. To assess the extensibility of targeting Wee1/CDK1 in GBM, patient-derived xenograft (PDX) cell lines were also treated with MK-1775. Although the response was more heterogeneous, on-target Wee1 inhibition led to decreased CDK1 Y15 phosphorylation and increased DNA damage and apoptosis in each line. These results were also validated in vivo, where single-agent MK-1775 demonstrated an antitumor effect on a flank PDX tumor model, increasing mouse survival by 1.74-fold. This study highlights the ability of unbiased quantitative phosphoproteomics to reveal therapeutic targets in tumor models, and the potential for Wee1 inhibition as a treatment approach in preclinical models of GBM. Mol Cancer Ther; 15(6); 1332-43. ©2016 AACR. ©2016 American Association for Cancer Research.

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.

High-accuracy identification and bioinformatic analysis of in vivo protein phosphorylation sites in yeast

DEFF Research Database (Denmark)

Gnad, Florian; de Godoy, Lyris M F; Cox, Jürgen

2009-01-01

Protein phosphorylation is a fundamental regulatory mechanism that affects many cell signaling processes. Using high-accuracy MS and stable isotope labeling in cell culture-labeling, we provide a global view of the Saccharomyces cerevisiae phosphoproteome, containing 3620 phosphorylation sites ma...

Robust, Sensitive, and Automated Phosphopeptide Enrichment Optimized for Low Sample Amounts Applied to Primary Hippocampal Neurons

NARCIS (Netherlands)

Post, Harm; Penning, Renske; Fitzpatrick, Martin; Garrigues, L.B.; Wu, W.; Mac Gillavry, H.D.; Hoogenraad, C.C.; Heck, A.J.R.; Altelaar, A.F.M.

2017-01-01

Because of the low stoichiometry of protein phosphorylation, targeted enrichment prior to LC–MS/MS analysis is still essential. The trend in phosphoproteome analysis is shifting toward an increasing number of biological replicates per experiment, ideally starting from very low sample amounts,

Optimized IMAC-IMAC protocol for phosphopeptide recovery from complex biological samples

DEFF Research Database (Denmark)

Ye, Juanying; Zhang, Xumin; Young, Clifford

2010-01-01

using Fe(III)-NTA IMAC resin and it proved to be highly selective in the phosphopeptide enrichment of a highly diluted standard sample (1:1000) prior to MALDI MS analysis. We also observed that a higher iron purity led to an increased IMAC enrichment efficiency. The optimized method was then adapted...... to phosphoproteome analyses of cell lysates of high protein complexity. From either 20 microg of mouse sample or 50 microg of Drosophila melanogaster sample, more than 1000 phosphorylation sites were identified in each study using IMAC-IMAC and LC-MS/MS. We demonstrate efficient separation of multiply phosphorylated...... characterization of phosphoproteins in functional phosphoproteomics research projects....

PhosphoSiteAnalyzer

DEFF Research Database (Denmark)

Bennetzen, Martin V; Cox, Jürgen; Mann, Matthias

2012-01-01

an algorithm to retrieve kinase predictions from the public NetworKIN webpage in a semiautomated way and applies hereafter advanced statistics to facilitate a user-tailored in-depth analysis of the phosphoproteomic data sets. The interface of the software provides a high degree of analytical flexibility......Phosphoproteomic experiments are routinely conducted in laboratories worldwide, and because of the fast development of mass spectrometric techniques and efficient phosphopeptide enrichment methods, researchers frequently end up having lists with tens of thousands of phosphorylation sites...... and is designed to be intuitive for most users. PhosphoSiteAnalyzer is a freeware program available at http://phosphosite.sourceforge.net ....

SAMNet: a network-based approach to integrate multi-dimensional high throughput datasets.

Science.gov (United States)

Gosline, Sara J C; Spencer, Sarah J; Ursu, Oana; Fraenkel, Ernest

2012-11-01

The rapid development of high throughput biotechnologies has led to an onslaught of data describing genetic perturbations and changes in mRNA and protein levels in the cell. Because each assay provides a one-dimensional snapshot of active signaling pathways, it has become desirable to perform multiple assays (e.g. mRNA expression and phospho-proteomics) to measure a single condition. However, as experiments expand to accommodate various cellular conditions, proper analysis and interpretation of these data have become more challenging. Here we introduce a novel approach called SAMNet, for Simultaneous Analysis of Multiple Networks, that is able to interpret diverse assays over multiple perturbations. The algorithm uses a constrained optimization approach to integrate mRNA expression data with upstream genes, selecting edges in the protein-protein interaction network that best explain the changes across all perturbations. The result is a putative set of protein interactions that succinctly summarizes the results from all experiments, highlighting the network elements unique to each perturbation. We evaluated SAMNet in both yeast and human datasets. The yeast dataset measured the cellular response to seven different transition metals, and the human dataset measured cellular changes in four different lung cancer models of Epithelial-Mesenchymal Transition (EMT), a crucial process in tumor metastasis. SAMNet was able to identify canonical yeast metal-processing genes unique to each commodity in the yeast dataset, as well as human genes such as β-catenin and TCF7L2/TCF4 that are required for EMT signaling but escaped detection in the mRNA and phospho-proteomic data. Moreover, SAMNet also highlighted drugs likely to modulate EMT, identifying a series of less canonical genes known to be affected by the BCR-ABL inhibitor imatinib (Gleevec), suggesting a possible influence of this drug on EMT.

Selective phosphorylation during early macrophage differentiation

KAUST Repository

Zhang, Huoming

2015-08-26

The differentiation of macrophages from monocytes is a tightly controlled and complex biological process. Although numerous studies have been conducted using biochemical approaches or global gene/gene profiling, the mechanisms of the early stages of differentiation remain unclear. Here we used SILAC-based quantitative proteomics approach to perform temporal phosphoproteome profiling of early macrophage differentiation. We identified a large set of phosphoproteins and grouped them as PMA-regulated and non-regulated phosphoproteins in the early stages of differentiation. Further analysis of the PMA-regulated phosphoproteins revealed that transcriptional suppression, cytoskeletal reorganization and cell adhesion were among the most significantly activated pathways. Some key involved regulators of these pathways are mTOR, MYB, STAT1 and CTNNB. Moreover, we were able to classify the roles and activities of several transcriptional factors during different differentiation stages and found that E2F is likely to be an important regulator during the relatively late stages of differentiation. This study provides the first comprehensive picture of the dynamic phosphoproteome during myeloid cells differentiation, and identifies potential molecular targets in leukemic cells.

Discovery of Novel Virulence Factors of Biothreat Agents: Validation of the Phosphoproteome-Based Approach

Science.gov (United States)

2008-06-30

systems that could serve as new targets for intervention and therapy . The comparative analysis of signaling profiles will further aid us in... chocolate agar plates. To confirm that infection over the 4 hour time-course used in the RPMA analysis does not cause apoptosis of THP-1 cells

Enrichment and separation of mono- and multiply phosphorylated peptides using sequential elution from IMAC prior to mass spectrometric analysis

DEFF Research Database (Denmark)

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

2009-01-01

Phospho-proteomics relies on methods for efficient purification and sequencing of phosphopeptides from highly complex biological systems using low amounts of starting material. Current methods for phosphopeptide enrichment, e.g., immobilized metal affinity chromatography and titanium dioxide chro...

Reactive Landing of Gas-Phase Ions as a Tool for the Fabrication of Metal Oxide Surfaces for In Situ Phosphopeptide Enrichment

Czech Academy of Sciences Publication Activity Database

Blacken, G. R.; Volný, Michael; Diener, M.; Jackson, K. E.; Ranjitkar, P.; Maly, D. J.; Tureček, F.

2009-01-01

Roč. 20, č. 6 (2009), s. 915-926 ISSN 1044-0305 Institutional research plan: CEZ:AV0Z50200510 Keywords : TANDEM MASS-SPECTROMETRY * SELECTIVE DETECTION * PHOSPHOPROTEOME ANALYSIS Subject RIV: EE - Microbiology, Virology Impact factor: 3.391, year: 2009

SimPhospho: a software tool enabling confident phosphosite assignment.

Science.gov (United States)

Suni, Veronika; Suomi, Tomi; Tsubosaka, Tomoya; Imanishi, Susumu Y; Elo, Laura L; Corthals, Garry L

2018-03-27

Mass spectrometry combined with enrichment strategies for phosphorylated peptides has been successfully employed for two decades to identify sites of phosphorylation. However, unambiguous phosphosite assignment is considered challenging. Given that site-specific phosphorylation events function as different molecular switches, validation of phosphorylation sites is of utmost importance. In our earlier study we developed a method based on simulated phosphopeptide spectral libraries, which enables highly sensitive and accurate phosphosite assignments. To promote more widespread use of this method, we here introduce a software implementation with improved usability and performance. We present SimPhospho, a fast and user-friendly tool for accurate simulation of phosphopeptide tandem mass spectra. Simulated phosphopeptide spectral libraries are used to validate and supplement database search results, with a goal to improve reliable phosphoproteome identification and reporting. The presented program can be easily used together with the Trans-Proteomic Pipeline and integrated in a phosphoproteomics data analysis workflow. SimPhospho is available for Windows, Linux and Mac operating systems at https://sourceforge.net/projects/simphospho/. It is open source and implemented in C ++. A user's manual with detailed description of data analysis using SimPhospho as well as test data can be found as supplementary material of this article. Supplementary data are available at https://www.btk.fi/research/ computational-biomedicine/software/.

Monitoring the native phosphorylation state of plasma membrane proteins from a single mouse cerebellum

DEFF Research Database (Denmark)

Schindler, J.; Ye, J. Y.; Jensen, Ole Nørregaard

2013-01-01

Neuronal processing in the cerebellum involves the phosphorylation and dephosphorylation of various plasma membrane proteins such as AMPA or NMDA receptors. Despite the importance of changes in phosphorylation pattern, no global phospho-proteome analysis has yet been performed. As plasma membrane...

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.

The phosphorylation pattern of bovine heart complex I subunits

DEFF Research Database (Denmark)

Palmisano, Giuseppe; Sardanelli, Anna Maria; Signorile, Anna

2007-01-01

The phosphoproteome of bovine heart complex I of the respiratory chain has been analysed with a procedure based on nondenaturing gel electrophoretic separation of complex I from small quantities of mitochondria samples, in-gel digestion, in combination with phosphopeptide enrichment by titanium d...

Global analysis of the yeast osmotic stress response by quantitative proteomics

DEFF Research Database (Denmark)

Soufi, Boumediene; Kelstrup, C.D.; Stoehr, G.

2009-01-01

a comprehensive, quantitative, and time-resolved analysis using high-resolution mass spectrometry of phospho-proteome and proteome changes in response to osmotic stress in yeast. We identified 5534 unique phosphopeptide variants and 3383 yeast proteins. More than 15% of the detected phosphorylation site status...... changed more than two-fold within 5 minutes of treatment. Many of the corresponding phosphoproteins are involved in the early response to environmental stress. Surprisingly, we find that 158 regulated phosphorylation sites are potential substrates of basophilic kinases as opposed to the classical proline......-directed MAP kinase network implicated in stress response mechanisms such as p38 and HOG pathways. Proteome changes reveal an increase in abundance of more than one hundred proteins after 20 min of salt stress. Many of these are involved in the cellular response to increased osmolarity, which include proteins...

Towards the systematic discovery of signal transduction networks using phosphorylation dynamics data

Directory of Open Access Journals (Sweden)

Yachie Nozomu

2010-05-01

Full Text Available Abstract Background Phosphorylation is a ubiquitous and fundamental regulatory mechanism that controls signal transduction in living cells. The number of identified phosphoproteins and their phosphosites is rapidly increasing as a result of recent mass spectrometry-based approaches. Results We analyzed time-course phosphoproteome data obtained previously by liquid chromatography mass spectrometry with the stable isotope labeling using amino acids in cell culture (SILAC method. This provides the relative phosphorylation activities of digested peptides at each of five time points after stimulating HeLa cells with epidermal growth factor (EGF. We initially calculated the correlations between the phosphorylation dynamics patterns of every pair of peptides and connected the strongly correlated pairs to construct a network. We found that peptides extracted from the same intracellular fraction (nucleus vs. cytoplasm tended to be close together within this phosphorylation dynamics-based network. The network was then analyzed using graph theory and compared with five known signal-transduction pathways. The dynamics-based network was correlated with known signaling pathways in the NetPath and Phospho.ELM databases, and especially with the EGF receptor (EGFR signaling pathway. Although the phosphorylation patterns of many proteins were drastically changed by the EGF stimulation, our results suggest that only EGFR signaling transduction was both strongly activated and precisely controlled. Conclusions The construction of a phosphorylation dynamics-based network provides a useful overview of condition-specific intracellular signal transduction using quantitative time-course phosphoproteome data under specific experimental conditions. Detailed prediction of signal transduction based on phosphoproteome dynamics remains challenging. However, since the phosphorylation profiles of kinase-substrate pairs on the specific pathway were localized in the dynamics-based

Effects of the NO/soluble guanylate cyclase/cGMP system on the functions of human platelets.

Science.gov (United States)

Makhoul, Stephanie; Walter, Elena; Pagel, Oliver; Walter, Ulrich; Sickmann, Albert; Gambaryan, Stepan; Smolenski, Albert; Zahedi, René P; Jurk, Kerstin

2018-06-01

Platelets are circulating sentinels of vascular integrity and are activated, inhibited, or modulated by multiple hormones, vasoactive substances or drugs. Endothelium- or drug-derived NO strongly inhibits platelet activation via activation of the soluble guanylate cyclase (sGC) and cGMP elevation, often in synergy with cAMP-elevation by prostacyclin. However, the molecular mechanisms and diversity of cGMP effects in platelets are poorly understood and sometimes controversial. Recently, we established the quantitative human platelet proteome, the iloprost/prostacyclin/cAMP/protein kinase A (PKA)-regulated phosphoproteome, and the interactions of the ADP- and iloprost/prostacyclin-affected phosphoproteome. We also showed that the sGC stimulator riociguat is in vitro a highly specific inhibitor, via cGMP, of various functions of human platelets. Here, we review the regulatory role of the cGMP/protein kinase G (PKG) system in human platelet function, and our current approaches to establish and analyze the phosphoproteome after selective stimulation of the sGC/cGMP pathway by NO donors and riociguat. Present data indicate an extensive and diverse NO/riociguat/cGMP phosphoproteome, which has to be compared with the cAMP phosphoproteome. In particular, sGC/cGMP-regulated phosphorylation of many membrane proteins, G-proteins and their regulators, signaling molecules, protein kinases, and proteins involved in Ca 2+ regulation, suggests that the sGC/cGMP system targets multiple signaling networks rather than a limited number of PKG substrate proteins. Copyright © 2018 Elsevier Inc. All rights reserved.

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

thaliana (Col-0) leaves using a two-phase partitioning system. The concentration of plasma membrane protein was determined by Bradford assay. Protein was digested with Lys-C for 4 hours and then by trypsin overnight. The peptide mixture was purified with IMAC, TiO2, CPP, SIMAC (IMAC+TiO2), the combination...

Activation of Bacillus subtilis Ugd by the BY-Kinase PtkA Proceeds via Phosphorylation of Its Residue Tyrosine 70

DEFF Research Database (Denmark)

Petranovic, Dina; Grangeasse, C.; Macek, B.

2009-01-01

-specific phosphoproteomic study indicated that tyrosine 70 is phosphorylated in the Bacillus subtilis UDP-glucose dehydrogenase Ugd. In this study we confirm that this tyrosine 70 is indeed the main residue phosphorylated by the cognate BY-kinase PtkA. Homology-based modeling of the Ugd structure using structures from UDP...

Quantitative Proteomic and Phosphoproteomic Analysis of Trypanosoma cruzi Amastigogenesis

DEFF Research Database (Denmark)

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

2014-01-01

Chagas disease is a tropical neglected disease endemic in Latin America and it is caused by the protozoan Trypanosoma cruzi. The parasite has four major life stages: epimastigote, metacyclic trypomastigote, bloodstream trypomastigote and amastigote. The differentiation from infective trypomastigo......Chagas disease is a tropical neglected disease endemic in Latin America and it is caused by the protozoan Trypanosoma cruzi. The parasite has four major life stages: epimastigote, metacyclic trypomastigote, bloodstream trypomastigote and amastigote. The differentiation from infective...

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.

PhosphOrtholog: a web-based tool for cross-species mapping of orthologous protein post-translational modifications.

Science.gov (United States)

Chaudhuri, Rima; Sadrieh, Arash; Hoffman, Nolan J; Parker, Benjamin L; Humphrey, Sean J; Stöckli, Jacqueline; Hill, Adam P; James, David E; Yang, Jean Yee Hwa

2015-08-19

Most biological processes are influenced by protein post-translational modifications (PTMs). Identifying novel PTM sites in different organisms, including humans and model organisms, has expedited our understanding of key signal transduction mechanisms. However, with increasing availability of deep, quantitative datasets in diverse species, there is a growing need for tools to facilitate cross-species comparison of PTM data. This is particularly important because functionally important modification sites are more likely to be evolutionarily conserved; yet cross-species comparison of PTMs is difficult since they often lie in structurally disordered protein domains. Current tools that address this can only map known PTMs between species based on known orthologous phosphosites, and do not enable the cross-species mapping of newly identified modification sites. Here, we addressed this by developing a web-based software tool, PhosphOrtholog ( www.phosphortholog.com ) that accurately maps protein modification sites between different species. This facilitates the comparison of datasets derived from multiple species, and should be a valuable tool for the proteomics community. Here we describe PhosphOrtholog, a web-based application for mapping known and novel orthologous PTM sites from experimental data obtained from different species. PhosphOrtholog is the only generic and automated tool that enables cross-species comparison of large-scale PTM datasets without relying on existing PTM databases. This is achieved through pairwise sequence alignment of orthologous protein residues. To demonstrate its utility we apply it to two sets of human and rat muscle phosphoproteomes generated following insulin and exercise stimulation, respectively, and one publicly available mouse phosphoproteome following cellular stress revealing high mapping and coverage efficiency. Although coverage statistics are dataset dependent, PhosphOrtholog increased the number of cross-species mapped sites

A Cell-Signaling Network Temporally Resolves Specific versus Promiscuous Phosphorylation

Directory of Open Access Journals (Sweden)

Evgeny Kanshin

2015-02-01

Full Text Available If specific and functional kinase- or phosphatase-substrate interactions are optimized for binding compared to promiscuous interactions, then changes in phosphorylation should occur faster on functional versus promiscuous substrates. To test this hypothesis, we designed a high temporal resolution global phosphoproteomics protocol to study the high-osmolarity glycerol (HOG response in the budding yeast Saccharomyces cerevisiae. The method provides accurate, stimulus-specific measurement of phosphoproteome changes, quantitative analysis of phosphodynamics at sub-minute temporal resolution, and detection of more phosphosites. Rates of evolution of dynamic phosphosites were comparable to those of known functional phosphosites and significantly lower than static or longer-time-frame dynamic phosphosites. Kinetic profile analyses indicated that putatively functional kinase- or phosphatase-substrate interactions occur more rapidly, within 60 s, than promiscuous interactions. Finally, we report many changes in phosphorylation of proteins implicated in cytoskeletal and mitotic spindle dynamics that may underlie regulation of cell cycle and morphogenesis.

Global protein phosphorylation dynamics during deoxynivalenol-induced ribotoxic stress response in the macrophage

Energy Technology Data Exchange (ETDEWEB)

Pan, Xiao [Department of Biochemistry and Molecular Biology, Michigan State University, East Lansing, MI 48824 (United States); Center for Integrative Toxicology, Michigan State University, East Lansing, MI 48824 (United States); Whitten, Douglas A. [Research Technology Support Facility, Proteomics Core, Michigan State University, East Lansing, MI 48824 (United States); Wu, Ming [Department of Computer Science and Engineering, Michigan State University, East Lansing, MI 48824 (United States); Chan, Christina [Department of Biochemistry and Molecular Biology, Michigan State University, East Lansing, MI 48824 (United States); Department of Computer Science and Engineering, Michigan State University, East Lansing, MI 48824 (United States); Wilkerson, Curtis G. [Department of Biochemistry and Molecular Biology, Michigan State University, East Lansing, MI 48824 (United States); Research Technology Support Facility, Proteomics Core, Michigan State University, East Lansing, MI 48824 (United States); Pestka, James J., E-mail: pestka@msu.edu [Center for Integrative Toxicology, Michigan State University, East Lansing, MI 48824 (United States); Department of Microbiology and Molecular Genetics, Michigan State University, East Lansing, MI 48824 (United States); Department of Food Science and Human Nutrition, Michigan State University, East Lansing, MI 48824 (United States)

2013-04-15

Deoxynivalenol (DON), a trichothecene mycotoxin produced by Fusarium that commonly contaminates food, is capable of activating mononuclear phagocytes of the innate immune system via a process termed the ribotoxic stress response (RSR). To encapture global signaling events mediating RSR, we quantified the early temporal (≤ 30 min) phosphoproteome changes that occurred in RAW 264.7 murine macrophage during exposure to a toxicologically relevant concentration of DON (250 ng/mL). Large-scale phosphoproteomic analysis employing stable isotope labeling of amino acids in cell culture (SILAC) in conjunction with titanium dioxide chromatography revealed that DON significantly upregulated or downregulated phosphorylation of 188 proteins at both known and yet-to-be functionally characterized phosphosites. DON-induced RSR is extremely complex and goes far beyond its prior known capacity to inhibit translation and activate MAPKs. Transcriptional regulation was the main target during early DON-induced RSR, covering over 20% of the altered phosphoproteins as indicated by Gene Ontology annotation and including transcription factors/cofactors and epigenetic modulators. Other biological processes impacted included cell cycle, RNA processing, translation, ribosome biogenesis, monocyte differentiation and cytoskeleton organization. Some of these processes could be mediated by signaling networks involving MAPK-, NFκB-, AKT- and AMPK-linked pathways. Fuzzy c-means clustering revealed that DON-regulated phosphosites could be discretely classified with regard to the kinetics of phosphorylation/dephosphorylation. The cellular response networks identified provide a template for further exploration of the mechanisms of trichothecenemycotoxins and other ribotoxins, and ultimately, could contribute to improved mechanism-based human health risk assessment. - Highlights: ► Mycotoxin deoxynivalenol (DON) induces immunotoxicity via ribotoxic stress response. ► SILAC phosphoproteomics using

Global protein phosphorylation dynamics during deoxynivalenol-induced ribotoxic stress response in the macrophage

International Nuclear Information System (INIS)

Pan, Xiao; Whitten, Douglas A.; Wu, Ming; Chan, Christina; Wilkerson, Curtis G.; Pestka, James J.

2013-01-01

Deoxynivalenol (DON), a trichothecene mycotoxin produced by Fusarium that commonly contaminates food, is capable of activating mononuclear phagocytes of the innate immune system via a process termed the ribotoxic stress response (RSR). To encapture global signaling events mediating RSR, we quantified the early temporal (≤ 30 min) phosphoproteome changes that occurred in RAW 264.7 murine macrophage during exposure to a toxicologically relevant concentration of DON (250 ng/mL). Large-scale phosphoproteomic analysis employing stable isotope labeling of amino acids in cell culture (SILAC) in conjunction with titanium dioxide chromatography revealed that DON significantly upregulated or downregulated phosphorylation of 188 proteins at both known and yet-to-be functionally characterized phosphosites. DON-induced RSR is extremely complex and goes far beyond its prior known capacity to inhibit translation and activate MAPKs. Transcriptional regulation was the main target during early DON-induced RSR, covering over 20% of the altered phosphoproteins as indicated by Gene Ontology annotation and including transcription factors/cofactors and epigenetic modulators. Other biological processes impacted included cell cycle, RNA processing, translation, ribosome biogenesis, monocyte differentiation and cytoskeleton organization. Some of these processes could be mediated by signaling networks involving MAPK-, NFκB-, AKT- and AMPK-linked pathways. Fuzzy c-means clustering revealed that DON-regulated phosphosites could be discretely classified with regard to the kinetics of phosphorylation/dephosphorylation. The cellular response networks identified provide a template for further exploration of the mechanisms of trichothecenemycotoxins and other ribotoxins, and ultimately, could contribute to improved mechanism-based human health risk assessment. - Highlights: ► Mycotoxin deoxynivalenol (DON) induces immunotoxicity via ribotoxic stress response. ► SILAC phosphoproteomics using

DTI analysis methods : Voxel-based analysis

NARCIS (Netherlands)

Van Hecke, Wim; Leemans, Alexander; Emsell, Louise

2016-01-01

Voxel-based analysis (VBA) of diffusion tensor imaging (DTI) data permits the investigation of voxel-wise differences or changes in DTI metrics in every voxel of a brain dataset. It is applied primarily in the exploratory analysis of hypothesized group-level alterations in DTI parameters, as it does

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

KAUST Repository

Chandramouli, Kondethimmanahalli; Mok, Flora SY; Wang, Hao; Qian, Pei-Yuan

2011-01-01

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

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

α-Cut method based importance measure for criticality analysis in fuzzy probability – Based fault tree analysis

International Nuclear Information System (INIS)

Purba, Julwan Hendry; Sony Tjahyani, D.T.; Widodo, Surip; Tjahjono, Hendro

2017-01-01

Highlights: •FPFTA deals with epistemic uncertainty using fuzzy probability. •Criticality analysis is important for reliability improvement. •An α-cut method based importance measure is proposed for criticality analysis in FPFTA. •The α-cut method based importance measure utilises α-cut multiplication, α-cut subtraction, and area defuzzification technique. •Benchmarking confirm that the proposed method is feasible for criticality analysis in FPFTA. -- Abstract: Fuzzy probability – based fault tree analysis (FPFTA) has been recently developed and proposed to deal with the limitations of conventional fault tree analysis. In FPFTA, reliabilities of basic events, intermediate events and top event are characterized by fuzzy probabilities. Furthermore, the quantification of the FPFTA is based on fuzzy multiplication rule and fuzzy complementation rule to propagate uncertainties from basic event to the top event. Since the objective of the fault tree analysis is to improve the reliability of the system being evaluated, it is necessary to find the weakest path in the system. For this purpose, criticality analysis can be implemented. Various importance measures, which are based on conventional probabilities, have been developed and proposed for criticality analysis in fault tree analysis. However, not one of those importance measures can be applied for criticality analysis in FPFTA, which is based on fuzzy probability. To be fully applied in nuclear power plant probabilistic safety assessment, FPFTA needs to have its corresponding importance measure. The objective of this study is to develop an α-cut method based importance measure to evaluate and rank the importance of basic events for criticality analysis in FPFTA. To demonstrate the applicability of the proposed measure, a case study is performed and its results are then benchmarked to the results generated by the four well known importance measures in conventional fault tree analysis. The results

Activation of EGFR and ERBB2 by Helicobacter pylori Results in Survival of Gastric Epithelial Cells with DNA Damage

Science.gov (United States)

Chaturvedi, Rupesh; Asim, Mohammad; Piazuelo, M. Blanca; Yan, Fang; Barry, Daniel P.; Sierra, Johanna Carolina; Delgado, Alberto G.; Hill, Salisha; Casero, Robert A.; Bravo, Luis E.; Dominguez, Ricardo L.; Correa, Pelayo; Polk, D. Brent; Washington, M. Kay; Rose, Kristie L.; Schey, Kevin L.; Morgan, Douglas R.; Peek, Richard M.; Wilson, Keith T.

2014-01-01

BACKGROUND & AIMS The gastric cancer-causing pathogen Helicobacter pylori upregulates spermine oxidase (SMOX) in gastric epithelial cells, causing oxidative stress-induced apoptosis and DNA damage. A subpopulation of SMOXhigh cells are resistant to apoptosis, despite their high levels of DNA damage. Because epidermal growth factor receptor (EGFR) activation can regulate apoptosis, we determined its role in SMOX-mediated effects. METHODS SMOX, apoptosis, and DNA damage were measured in gastric epithelial cells from H pylori-infected Egfrwa5 mice (which have attenuated EGFR activity), Egfr wild-type mice, or in infected cells incubated with EGFR inhibitors or deficient in EGFR. Phosphoproteomic analysis was performed. Two independent tissue microarrays containing each stage of disease, from gastritis to carcinoma, and gastric biopsies from Colombian and Honduran cohorts were analyzed by immunohistochemistry. RESULTS SMOX expression and DNA damage were decreased, and apoptosis increased in H pylori-infected Egfrwa5 mice. H pylori-infected cells with deletion or inhibition of EGFR had reduced levels of SMOX, DNA damage, and DNA damagehigh apoptosislow cells. Phosphoproteomic analysis revealed increased EGFR and ERBB2 signaling. Immunoblot analysis demonstrated the presence of a phosphorylated (p)EGFR–ERBB2 heterodimer and pERBB2; knockdown of ErbB2 facilitated apoptosis of DNA damagehigh apoptosislow cells. SMOX was increased in all stages of gastric disease, peaking in tissues with intestinal metaplasia, whereas pEGFR, pEGFR–ERBB2, and pERBB2 were increased predominantly in tissues demonstrating gastritis or atrophic gastritis. Principal component analysis separated gastritis tissues from patients with cancer vs those without cancer. pEGFR, pEGFR–ERBB2, pERBB2, and SMOX were increased in gastric samples from patients whose disease progressed to intestinal metaplasia or dysplasia, compared with patients whose disease did not progress. CONCLUSIONS In an analysis

Using Proteomics To Elucidate Critical Signaling Pathways

KAUST Repository

Ahmed, Heba

2012-11-01

Despite important advances in the therapy of acute myeloid leukemia (AML) the majority of patients will die from their disease (Appelbaum, Rowe, Radich, & Dick, 2001). Characterization of the aberrant molecular pathways responsible for this malignancy provides a platform to discover alternative treatments to help alter the fate of patients. AML is characterized by a blockage in the differentiation of myeloid cells resulting in the accumulation of highly proliferating immature hematopoietic cells. Since treatments such as chemotherapy rarely destroy the leukemic cells entirely, differentiation induction therapy has become a very attractive treatment option. Interestingly, previous experiments have shown that ligation of CD44, a cell surface glycoprotein strongly expressed on all AML cells, with anti-CD44 monoclonal antibodies (mAbs) could reverse this block in differentiation of leukemic blasts regardless of the AML subtype. To expand the understanding of the cellular regulation and circuitry involved, we aim to apply quantitative phosphoproteomics to monitor dynamic changes in phosphorylation state in response to anti-CD44 treatment. Protein phosphorylation and dephosphorylation is a highly controlled biochemical process that responds to various intracellular and extracellular stimuli. As phosphorylation is a dynamic process, quantification of these phosphorylation events would be vastly insightful. The main objective of this project is to determine the differentiation-dependent phosphoproteome of AML cells upon treatment of cells with the anti-CD44 mAb.In these experiments, optimization of protein extraction, phosphopeptide enrichment and data processing and analysis has been achieved. The primary results show successful phosphoproteome extraction complemented with efficient phosphopeptide enrichment and informative data processing. Further quantification with stable isotope labeling techniques is anticipated to provide candidates for targeted therapy.

Frame-based safety analysis approach for decision-based errors

International Nuclear Information System (INIS)

Fan, Chin-Feng; Yihb, Swu

1997-01-01

A frame-based approach is proposed to analyze decision-based errors made by automatic controllers or human operators due to erroneous reference frames. An integrated framework, Two Frame Model (TFM), is first proposed to model the dynamic interaction between the physical process and the decision-making process. Two important issues, consistency and competing processes, are raised. Consistency between the physical and logic frames makes a TFM-based system work properly. Loss of consistency refers to the failure mode that the logic frame does not accurately reflect the state of the controlled processes. Once such failure occurs, hazards may arise. Among potential hazards, the competing effect between the controller and the controlled process is the most severe one, which may jeopardize a defense-in-depth design. When the logic and physical frames are inconsistent, conventional safety analysis techniques are inadequate. We propose Frame-based Fault Tree; Analysis (FFTA) and Frame-based Event Tree Analysis (FETA) under TFM to deduce the context for decision errors and to separately generate the evolution of the logical frame as opposed to that of the physical frame. This multi-dimensional analysis approach, different from the conventional correctness-centred approach, provides a panoramic view in scenario generation. Case studies using the proposed techniques are also given to demonstrate their usage and feasibility

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.

Trajectory Based Traffic Analysis

DEFF Research Database (Denmark)

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

2013-01-01

We present the INTRA system for interactive path-based traffic analysis. The analyses are developed in collaboration with traffic researchers and provide novel insights into conditions such as congestion, travel-time, choice of route, and traffic-flow. INTRA supports interactive point-and-click a......We present the INTRA system for interactive path-based traffic analysis. The analyses are developed in collaboration with traffic researchers and provide novel insights into conditions such as congestion, travel-time, choice of route, and traffic-flow. INTRA supports interactive point......-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...

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

of human MCF10A cells. Proteomics 2011, 11 (10), 2019−26. (23) Siu, S. O.; Lam , M. P.; Lau , E.; Kong, R. P.; Lee, S. M.; Chu, I. K. Fully automatable...signaling. J. Proteome Res. 2011, 10 (12), 5383−97. (17) Kettenbach, A. N .; Gerber, S. A. Rapid and reproducible single- stage phosphopeptide enrichment of...McGowan, T.; Bandhakavi, S.; Cheng, B.; Rhodus, N . L.; Griffin, T. J. Large-scale phosphoproteomics Journal of Proteome Research Article dx.doi.org

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.

Systematic inference of functional phosphorylation events in yeast metabolism.

Science.gov (United States)

Chen, Yu; Wang, Yonghong; Nielsen, Jens

2017-07-01

Protein phosphorylation is a post-translational modification that affects proteins by changing their structure and conformation in a rapid and reversible way, and it is an important mechanism for metabolic regulation in cells. Phosphoproteomics enables high-throughput identification of phosphorylation events on metabolic enzymes, but identifying functional phosphorylation events still requires more detailed biochemical characterization. Therefore, development of computational methods for investigating unknown functions of a large number of phosphorylation events identified by phosphoproteomics has received increased attention. We developed a mathematical framework that describes the relationship between phosphorylation level of a metabolic enzyme and the corresponding flux through the enzyme. Using this framework, it is possible to quantitatively estimate contribution of phosphorylation events to flux changes. We showed that phosphorylation regulation analysis, combined with a systematic workflow and correlation analysis, can be used for inference of functional phosphorylation events in steady and dynamic conditions, respectively. Using this analysis, we assigned functionality to phosphorylation events of 17 metabolic enzymes in the yeast Saccharomyces cerevisiae , among which 10 are novel. Phosphorylation regulation analysis cannot only be extended for inference of other functional post-translational modifications but also be a promising scaffold for multi-omics data integration in systems biology. Matlab codes for flux balance analysis in this study are available in Supplementary material. yhwang@ecust.edu.cn or nielsenj@chalmers.se. Supplementary data are available at Bioinformatics online. © The Author 2017. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

Quantitative phosphoproteomic analysis of early alterations in protein phosphorylation by 2,3,7,8-tetrachlorodibenzo-p-dioxin

DEFF Research Database (Denmark)

Schulz, Melanie; Brandner, Stefanie; Eberhagen, Carola

2013-01-01

A comprehensive quantitative analysis of changes in protein phosphorylation preceding or accompanying transcriptional activation by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in 5L rat hepatoma cells was performed using the SILAC approach. Following exposure of the cells to DMSO or 1 nM TCDD for 0......-induced gene activation, regulators of small GTPases of the Ras superfamily, UBX domain-containing proteins and the oncogenic protein LYRIC. The results open up new directions for research on the molecular mechanisms of dioxin action and toxicity....

Announcing the Launch of CPTAC’s Proteogenomics DREAM Challenge | Office of Cancer Clinical Proteomics Research

Science.gov (United States)

This week, we are excited to announce the launch of the National Cancer Institute’s Clinical Proteomic Tumor Analysis Consortium (CPTAC) Proteogenomics Computational DREAM Challenge.  The aim of this Challenge is to encourage the generation of computational methods for extracting information from the cancer proteome and for linking those data to genomic and transcriptomic information.  The specific goals are to predict proteomic and phosphoproteomic data from other multiple data types including transcriptomics and genetics.

UNcleProt (Universal Nuclear Protein database of barley): The first nuclear protein database that distinguishes proteins from different phases of the cell cycle

Czech Academy of Sciences Publication Activity Database

Blavet, Nicolas; Uřinovská, J.; Jeřábková, Hana; Chamrád, I.; Vrána, Jan; Lenobel, R.; Beinhauer, D.; Šebela, M.; Doležel, Jaroslav; Petrovská, Beáta

2017-01-01

Roč. 8, č. 1 (2017), s. 70-80 ISSN 1949-1034 R&D Projects: GA ČR(CZ) GA14-28443S; GA MŠk(CZ) LO1204 Institutional support: RVO:61389030 Keywords : cicer-arietinum l. * rice oryza-sativa * chromatin-associated protein s * proteomic analysis * mitotic chromosomes * dehydration * localization * chickpea * network * phosphoproteome * barley * cell cycle * database * flow-cytometry * localization * mass spectrometry * nuclear proteome * nucleus Subject RIV: CE - Biochemistry OBOR OECD: Cell biology Impact factor: 2.387, year: 2016

Adaptation of HepG2 cells to a steady-state reduction in the content of protein phosphatase 6 (PP6) catalytic subunit

Energy Technology Data Exchange (ETDEWEB)

Boylan, Joan M. [Department of Pediatrics, Brown University and Rhode Island Hospital, Providence, RI (United States); Salomon, Arthur R. [Department of Molecular Biology, Cell Biology and Biochemistry, Brown University, Providence, RI (United States); Department of Chemistry, Brown University, Providence, RI (United States); Tantravahi, Umadevi [Division of Genetics, Department of Pathology, Brown University and Women and Infants Hospital, Providence, RI (United States); Gruppuso, Philip A., E-mail: philip_gruppuso@brown.edu [Department of Pediatrics, Brown University and Rhode Island Hospital, Providence, RI (United States); Department of Molecular Biology, Cell Biology and Biochemistry, Brown University, Providence, RI (United States)

2015-07-15

Protein phosphatase 6 (PP6) is a ubiquitous Ser/Thr phosphatase involved in an array of cellular processes. To assess the potential of PP6 as a therapeutic target in liver disorders, we attenuated expression of the PP6 catalytic subunit in HepG2 cells using lentiviral-transduced shRNA. Two PP6 knock-down (PP6KD) cell lines (90% reduction of PP6-C protein content) were studied in depth. Both proliferated at a rate similar to control cells. However, flow cytometry indicated G2/M cell cycle arrest that was accounted for by a shift of the cells from a diploid to tetraploid state. PP6KD cells did not show an increase in apoptosis, nor did they exhibit reduced viability in the presence of bleomycin or taxol. Gene expression analysis by microarray showed attenuated anti-inflammatory signaling. Genes associated with DNA replication were downregulated. Mass spectrometry-based phosphoproteomic analysis yielded 80 phosphopeptides representing 56 proteins that were significantly affected by a stable reduction in PP6-C. Proteins involved in DNA replication, DNA damage repair and pre-mRNA splicing were overrepresented among these. PP6KD cells showed intact mTOR signaling. Our studies demonstrated involvement of PP6 in a diverse set of biological pathways and an adaptive response that may limit the effectiveness of targeting PP6 in liver disorders. - Highlights: • Lentiviral-transduced shRNA was used to generate a stable knockdown of PP6 in HepG2 cells. • Cells adapted to reduced PP6; cell proliferation was unaffected, and cell survival was normal. • However, PP6 knockdown was associated with a transition to a tetraploid state. • Genomic profiling showed downregulated anti-inflammatory signaling and DNA replication. • Phosphoproteomic profiling showed changes in proteins associated with DNA replication and repair.

Adaptation of HepG2 cells to a steady-state reduction in the content of protein phosphatase 6 (PP6) catalytic subunit

International Nuclear Information System (INIS)

Boylan, Joan M.; Salomon, Arthur R.; Tantravahi, Umadevi; Gruppuso, Philip A.

2015-01-01

Protein phosphatase 6 (PP6) is a ubiquitous Ser/Thr phosphatase involved in an array of cellular processes. To assess the potential of PP6 as a therapeutic target in liver disorders, we attenuated expression of the PP6 catalytic subunit in HepG2 cells using lentiviral-transduced shRNA. Two PP6 knock-down (PP6KD) cell lines (90% reduction of PP6-C protein content) were studied in depth. Both proliferated at a rate similar to control cells. However, flow cytometry indicated G2/M cell cycle arrest that was accounted for by a shift of the cells from a diploid to tetraploid state. PP6KD cells did not show an increase in apoptosis, nor did they exhibit reduced viability in the presence of bleomycin or taxol. Gene expression analysis by microarray showed attenuated anti-inflammatory signaling. Genes associated with DNA replication were downregulated. Mass spectrometry-based phosphoproteomic analysis yielded 80 phosphopeptides representing 56 proteins that were significantly affected by a stable reduction in PP6-C. Proteins involved in DNA replication, DNA damage repair and pre-mRNA splicing were overrepresented among these. PP6KD cells showed intact mTOR signaling. Our studies demonstrated involvement of PP6 in a diverse set of biological pathways and an adaptive response that may limit the effectiveness of targeting PP6 in liver disorders. - Highlights: • Lentiviral-transduced shRNA was used to generate a stable knockdown of PP6 in HepG2 cells. • Cells adapted to reduced PP6; cell proliferation was unaffected, and cell survival was normal. • However, PP6 knockdown was associated with a transition to a tetraploid state. • Genomic profiling showed downregulated anti-inflammatory signaling and DNA replication. • Phosphoproteomic profiling showed changes in proteins associated with DNA replication and repair

Reliability analysis of software based safety functions

International Nuclear Information System (INIS)

Pulkkinen, U.

1993-05-01

The methods applicable in the reliability analysis of software based safety functions are described in the report. Although the safety functions also include other components, the main emphasis in the report is on the reliability analysis of software. The check list type qualitative reliability analysis methods, such as failure mode and effects analysis (FMEA), are described, as well as the software fault tree analysis. The safety analysis based on the Petri nets is discussed. The most essential concepts and models of quantitative software reliability analysis are described. The most common software metrics and their combined use with software reliability models are discussed. The application of software reliability models in PSA is evaluated; it is observed that the recent software reliability models do not produce the estimates needed in PSA directly. As a result from the study some recommendations and conclusions are drawn. The need of formal methods in the analysis and development of software based systems, the applicability of qualitative reliability engineering methods in connection to PSA and the need to make more precise the requirements for software based systems and their analyses in the regulatory guides should be mentioned. (orig.). (46 refs., 13 figs., 1 tab.)

The Arabidopsis TOR Kinase Specifically Regulates the Expression of Nuclear Genes Coding for Plastidic Ribosomal Proteins and the Phosphorylation of the Cytosolic Ribosomal Protein S6.

Science.gov (United States)

Dobrenel, Thomas; Mancera-Martínez, Eder; Forzani, Céline; Azzopardi, Marianne; Davanture, Marlène; Moreau, Manon; Schepetilnikov, Mikhail; Chicher, Johana; Langella, Olivier; Zivy, Michel; Robaglia, Christophe; Ryabova, Lyubov A; Hanson, Johannes; Meyer, Christian

2016-01-01

Protein translation is an energy consuming process that has to be fine-tuned at both the cell and organism levels to match the availability of resources. The target of rapamycin kinase (TOR) is a key regulator of a large range of biological processes in response to environmental cues. In this study, we have investigated the effects of TOR inactivation on the expression and regulation of Arabidopsis ribosomal proteins at different levels of analysis, namely from transcriptomic to phosphoproteomic. TOR inactivation resulted in a coordinated down-regulation of the transcription and translation of nuclear-encoded mRNAs coding for plastidic ribosomal proteins, which could explain the chlorotic phenotype of the TOR silenced plants. We have identified in the 5' untranslated regions (UTRs) of this set of genes a conserved sequence related to the 5' terminal oligopyrimidine motif, which is known to confer translational regulation by the TOR kinase in other eukaryotes. Furthermore, the phosphoproteomic analysis of the ribosomal fraction following TOR inactivation revealed a lower phosphorylation of the conserved Ser240 residue in the C-terminal region of the 40S ribosomal protein S6 (RPS6). These results were confirmed by Western blot analysis using an antibody that specifically recognizes phosphorylated Ser240 in RPS6. Finally, this antibody was used to follow TOR activity in plants. Our results thus uncover a multi-level regulation of plant ribosomal genes and proteins by the TOR kinase.

2D-HPLC-MS phosphoproteomics analysis of lung and breast carcinomas

International Nuclear Information System (INIS)

Rocco, M.; Rubartelli, A.

2009-01-01

The project was conceived as two phases. In the first phase, we planned to validate markers, or expression patterns, previously described in the literature as being characteristic of specific tumors. In a second phase, a search for new markers associated with different tumors was to be carried on, developing new 2D-HPLC methods coupled with API-ESI mass spectrometry, with the ultimate goal of their rapid identification in biological specimens. For what concerns the first phase, the most relevant data are described in (Ceccarelli et al., 2008) and further analyzed in (Rubartelli et al., 2007). In these studies, we have compared the synthesis and intracellular accumulation levels of two oxido-reductases having also an extracellular cytokine function, the macrophage inhibitory factor (MIF) and thioredoxin (Trx)

A collection of open source applications for mass spectrometry data mining.

Science.gov (United States)

Gallardo, Óscar; Ovelleiro, David; Gay, Marina; Carrascal, Montserrat; Abian, Joaquin

2014-10-01

We present several bioinformatics applications for the identification and quantification of phosphoproteome components by MS. These applications include a front-end graphical user interface that combines several Thermo RAW formats to MASCOT™ Generic Format extractors (EasierMgf), two graphical user interfaces for search engines OMSSA and SEQUEST (OmssaGui and SequestGui), and three applications, one for the management of databases in FASTA format (FastaTools), another for the integration of search results from up to three search engines (Integrator), and another one for the visualization of mass spectra and their corresponding database search results (JsonVisor). These applications were developed to solve some of the common problems found in proteomic and phosphoproteomic data analysis and were integrated in the workflow for data processing and feeding on our LymPHOS database. Applications were designed modularly and can be used standalone. These tools are written in Perl and Python programming languages and are supported on Windows platforms. They are all released under an Open Source Software license and can be freely downloaded from our software repository hosted at GoogleCode. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Quantitative Analysis of Signaling Networks across Differentially Embedded Tumors Highlights Interpatient Heterogeneity in Human Glioblastoma

Science.gov (United States)

2015-01-01

Glioblastoma multiforme (GBM) is the most aggressive malignant primary brain tumor, with a dismal mean survival even with the current standard of care. Although in vitro cell systems can provide mechanistic insight into the regulatory networks governing GBM cell proliferation and migration, clinical samples provide a more physiologically relevant view of oncogenic signaling networks. However, clinical samples are not widely available and may be embedded for histopathologic analysis. With the goal of accurately identifying activated signaling networks in GBM tumor samples, we investigated the impact of embedding in optimal cutting temperature (OCT) compound followed by flash freezing in LN2 vs immediate flash freezing (iFF) in LN2 on protein expression and phosphorylation-mediated signaling networks. Quantitative proteomic and phosphoproteomic analysis of 8 pairs of tumor specimens revealed minimal impact of the different sample processing strategies and highlighted the large interpatient heterogeneity present in these tumors. Correlation analyses of the differentially processed tumor sections identified activated signaling networks present in selected tumors and revealed the differential expression of transcription, translation, and degradation associated proteins. This study demonstrates the capability of quantitative mass spectrometry for identification of in vivo oncogenic signaling networks from human tumor specimens that were either OCT-embedded or immediately flash-frozen. PMID:24927040

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.

Proteomics Reveals Global Regulation of Protein SUMOylation by ATM and ATR Kinases during Replication Stress

DEFF Research Database (Denmark)

Munk, Stephanie; Sigurðsson, Jón Otti; Xiao, Zhenyu

2017-01-01

The mechanisms that protect eukaryotic DNA during the cumbersome task of replication depend on the precise coordination of several post-translational modification (PTM)-based signaling networks. Phosphorylation is a well-known regulator of the replication stress response, and recently an essentia....... They analyze changes in the SUMO and phosphoproteome after MMC and hydroxyurea treatments and find that the DNA damage response kinases ATR and ATM globally regulate SUMOylation upon replication stress and fork breakage....

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

Phospho.ELM: a database of phosphorylation sites--update 2011

DEFF Research Database (Denmark)

Dinkel, Holger; Chica, Claudia; Via, Allegra

2011-01-01

The Phospho.ELM resource (http://phospho.elm.eu.org) is a relational database designed to store in vivo and in vitro phosphorylation data extracted from the scientific literature and phosphoproteomic analyses. The resource has been actively developed for more than 7 years and currently comprises ...... sequence alignment used for the score calculation. Finally, special emphasis has been put on linking to external resources such as interaction networks and other databases.......The Phospho.ELM resource (http://phospho.elm.eu.org) is a relational database designed to store in vivo and in vitro phosphorylation data extracted from the scientific literature and phosphoproteomic analyses. The resource has been actively developed for more than 7 years and currently comprises 42...

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

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

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.

TIMP-1 increases expression and phosphorylation of proteins associated with drug resistance in breast cancer cells

DEFF Research Database (Denmark)

Hekmat, Omid; Munk, Stephanie; Fogh, Louise

2013-01-01

may explain the resistance phenotype to topoisomerase inhibitors that was observed in cells with high TIMP-1 levels. Pathway analysis showed an enrichment of proteins from functional categories such as apoptosis, cell cycle, DNA repair, transcription factors, drug targets and proteins associated......Tissue inhibitor of metalloproteinase 1 (TIMP-1) is a protein with a potential biological role in drug resistance. To elucidate the unknown molecular mechanisms underlying the association between high TIMP-1 levels and increased chemotherapy resistance, we employed SILAC-based quantitative mass...... spectrometry to analyze global proteome and phosphoproteome differences of MCF-7 breast cancer cells expressing high or low levels of TIMP-1. In TIMP-1 high expressing cells, 312 proteins and 452 phosphorylation sites were up-regulated. Among these were the cancer drug targets topoisomerase 1, 2A and 2B, which...

Plug-in Based Analysis Framework for LHC Post-Mortem Analysis

CERN Document Server

Gorbonosov, R; Zerlauth, M; Baggiolini, V

2014-01-01

Plug-in based software architectures [1] are extensible, enforce modularity and allow several teams to work in parallel. But they have certain technical and organizational challenges, which we discuss in this paper. We gained our experience when developing the Post-Mortem Analysis (PMA) system, which is a mission critical system for the Large Hadron Collider (LHC). We used a plugin-based architecture with a general-purpose analysis engine, for which physicists and equipment experts code plugins containing the analysis algorithms. We have over 45 analysis plugins developed by a dozen of domain experts. This paper focuses on the design challenges we faced in order to mitigate the risks of executing third-party code: assurance that even a badly written plugin doesn't perturb the work of the overall application; plugin execution control which allows to detect plugin misbehaviour and react; robust communication mechanism between plugins, diagnostics facilitation in case of plugin failure; testing of the plugins be...

Survey of activated FLT3 signaling in leukemia.

Directory of Open Access Journals (Sweden)

Ting-lei Gu

Full Text Available Activating mutations of FMS-like tyrosine kinase-3 (FLT3 are found in approximately 30% of patients with acute myeloid leukemia (AML. FLT3 is therefore an attractive drug target. However, the molecular mechanisms by which FLT3 mutations lead to cell transformation in AML remain unclear. To develop a better understanding of FLT3 signaling as well as its downstream effectors, we performed detailed phosphoproteomic analysis of FLT3 signaling in human leukemia cells. We identified over 1000 tyrosine phosphorylation sites from about 750 proteins in both AML (wild type and mutant FLT3 and B cell acute lymphoblastic leukemia (normal and amplification of FLT3 cell lines. Furthermore, using stable isotope labeling by amino acids in cell culture (SILAC, we were able to quantified over 400 phosphorylation sites (pTyr, pSer, and pThr that were responsive to FLT3 inhibition in FLT3 driven human leukemia cell lines. We also extended this phosphoproteomic analysis on bone marrow from primary AML patient samples, and identify over 200 tyrosine and 800 serine/threonine phosphorylation sites in vivo. This study showed that oncogenic FLT3 regulates proteins involving diverse cellular processes and affects multiple signaling pathways in human leukemia that we previously appreciated, such as Fc epsilon RI-mediated signaling, BCR, and CD40 signaling pathways. It provides a valuable resource for investigation of oncogenic FLT3 signaling in human leukemia.

An SQL-based approach to physics analysis

International Nuclear Information System (INIS)

Limper, Dr Maaike

2014-01-01

As part of the CERN openlab collaboration a study was made into the possibility of performing analysis of the data collected by the experiments at the Large Hadron Collider (LHC) through SQL-queries on data stored in a relational database. Currently LHC physics analysis is done using data stored in centrally produced 'ROOT-ntuple' files that are distributed through the LHC computing grid. The SQL-based approach to LHC physics analysis presented in this paper allows calculations in the analysis to be done at the database and can make use of the database's in-built parallelism features. Using this approach it was possible to reproduce results for several physics analysis benchmarks. The study shows the capability of the database to handle complex analysis tasks but also illustrates the limits of using row-based storage for storing physics analysis data, as performance was limited by the I/O read speed of the system.

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)

Space shuttle booster multi-engine base flow analysis

Science.gov (United States)

Tang, H. H.; Gardiner, C. R.; Anderson, W. A.; Navickas, J.

1972-01-01

A comprehensive review of currently available techniques pertinent to several prominent aspects of the base thermal problem of the space shuttle booster is given along with a brief review of experimental results. A tractable engineering analysis, capable of predicting the power-on base pressure, base heating, and other base thermal environmental conditions, such as base gas temperature, is presented and used for an analysis of various space shuttle booster configurations. The analysis consists of a rational combination of theoretical treatments of the prominent flow interaction phenomena in the base region. These theories consider jet mixing, plume flow, axisymmetric flow effects, base injection, recirculating flow dynamics, and various modes of heat transfer. Such effects as initial boundary layer expansion at the nozzle lip, reattachment, recompression, choked vent flow, and nonisoenergetic mixing processes are included in the analysis. A unified method was developed and programmed to numerically obtain compatible solutions for the various flow field components in both flight and ground test conditions. Preliminary prediction for a 12-engine space shuttle booster base thermal environment was obtained for a typical trajectory history. Theoretical predictions were also obtained for some clustered-engine experimental conditions. Results indicate good agreement between the data and theoretical predicitons.

From Phosphosites to Kinases

DEFF Research Database (Denmark)

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

2016-01-01

Kinases play a pivotal role in propagating the phosphorylation-mediated signaling networks in living cells. With the overwhelming quantities of phosphoproteomics data being generated, the number of identified phosphorylation sites (phosphosites) is ever increasing. Often, proteomics investigations...... sequence motifs, mostly based on large scale in vivo and in vitro experiments. The context of the kinase and the phosphorylated proteins in a biological system is equally important for predicting association between the enzymes and substrates, an aspect that is also being tackled with available...

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.

Survey of sampling-based methods for uncertainty and sensitivity analysis

International Nuclear Information System (INIS)

Helton, J.C.; Johnson, J.D.; Sallaberry, C.J.; Storlie, C.B.

2006-01-01

Sampling-based methods for uncertainty and sensitivity analysis are reviewed. The following topics are considered: (i) definition of probability distributions to characterize epistemic uncertainty in analysis inputs (ii) generation of samples from uncertain analysis inputs (iii) propagation of sampled inputs through an analysis (iv) presentation of uncertainty analysis results, and (v) determination of sensitivity analysis results. Special attention is given to the determination of sensitivity analysis results, with brief descriptions and illustrations given for the following procedures/techniques: examination of scatterplots, correlation analysis, regression analysis, partial correlation analysis, rank transformations, statistical tests for patterns based on gridding, entropy tests for patterns based on gridding, nonparametric regression analysis, squared rank differences/rank correlation coefficient test, two-dimensional Kolmogorov-Smirnov test, tests for patterns based on distance measures, top down coefficient of concordance, and variance decomposition

Survey of sampling-based methods for uncertainty and sensitivity analysis.

Energy Technology Data Exchange (ETDEWEB)

Johnson, Jay Dean; Helton, Jon Craig; Sallaberry, Cedric J. PhD. (.; .); Storlie, Curt B. (Colorado State University, Fort Collins, CO)

2006-06-01

Sampling-based methods for uncertainty and sensitivity analysis are reviewed. The following topics are considered: (1) Definition of probability distributions to characterize epistemic uncertainty in analysis inputs, (2) Generation of samples from uncertain analysis inputs, (3) Propagation of sampled inputs through an analysis, (4) Presentation of uncertainty analysis results, and (5) Determination of sensitivity analysis results. Special attention is given to the determination of sensitivity analysis results, with brief descriptions and illustrations given for the following procedures/techniques: examination of scatterplots, correlation analysis, regression analysis, partial correlation analysis, rank transformations, statistical tests for patterns based on gridding, entropy tests for patterns based on gridding, nonparametric regression analysis, squared rank differences/rank correlation coefficient test, two dimensional Kolmogorov-Smirnov test, tests for patterns based on distance measures, top down coefficient of concordance, and variance decomposition.

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

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

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...

Identification of Phosphorylated Proteins on a Global Scale.

Science.gov (United States)

Iliuk, Anton

2018-05-31

Liquid chromatography (LC) coupled with tandem mass spectrometry (MS/MS) has enabled researchers to analyze complex biological samples with unprecedented depth. It facilitates the identification and quantification of modifications within thousands of proteins in a single large-scale proteomic experiment. Analysis of phosphorylation, one of the most common and important post-translational modifications, has particularly benefited from such progress in the field. Here, detailed protocols are provided for a few well-regarded, common sample preparation methods for an effective phosphoproteomic experiment. © 2018 by John Wiley & Sons, Inc. Copyright © 2018 John Wiley & Sons, Inc.

Quantitative phosphoproteomics applied to the yeast pheromone signaling pathway

DEFF Research Database (Denmark)

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

2005-01-01

of a detailed molecular view of complex biological processes. We present a quantitative modification-specific proteomic approach that combines stable isotope labeling by amino acids in cell culture (SILAC) for quantitation with IMAC for phosphopeptide enrichment and three stages of mass spectrometry (MS....... 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...

Phosphoproteome analysis of streptomyces development reveals extensive protein phosphorylation accompanying bacterial differentiation

DEFF Research Database (Denmark)

Manteca, Angel; Ye, Juanying; Sánchez, Jesús

2011-01-01

Streptomycetes are bacterial species that undergo a complex developmental cycle that includes programmed cell death (PCD) events and sporulation. They are widely used in biotechnology because they produce most clinically relevant secondary metabolites. Although Streptomyces coelicolor is one...... events were detected during the presporulation and sporulation stages (80%). Most of these phosphorylations were not reported before in Streptomyces, and included sporulation factors, transcriptional regulators, protein kinases and other regulatory proteins. Several of the identified phosphorylated...... proteins, FtsZ, DivIVA, and FtsH2, were previously demonstrated to be involved in the sporulation process. We thus established for the first time the widespread occurrence and dynamic features of Ser/Thr/Tyr protein phosphorylation in a bacteria species and also revealed a previously unrecognized...

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

Identification and quantitation of signal molecule-dependent protein phosphorylation

KAUST Repository

Groen, Arnoud J.

2013-09-03

Phosphoproteomics is a fast-growing field that aims at characterizing phosphorylated proteins in a cell or a tissue at a given time. Phosphorylation of proteins is an important regulatory mechanism in many cellular processes. Gel-free phosphoproteome technique involving enrichment of phosphopeptide coupled with mass spectrometry has proven to be invaluable to detect and characterize phosphorylated proteins. In this chapter, a gel-free quantitative approach involving 15N metabolic labelling in combination with phosphopeptide enrichment by titanium dioxide (TiO2) and their identification by MS is described. This workflow can be used to gain insights into the role of signalling molecules such as cyclic nucleotides on regulatory networks through the identification and quantification of responsive phospho(proteins). © Springer Science+Business Media New York 2013.

Flux control through protein phosphorylation in yeast

DEFF Research Database (Denmark)

Chen, Yu; Nielsen, Jens

2016-01-01

Protein phosphorylation is one of the most important mechanisms regulating metabolism as it can directly modify metabolic enzymes by the addition of phosphate groups. Attributed to such a rapid and reversible mechanism, cells can adjust metabolism rapidly in response to temporal changes. The yeast...... as well as identify mechanisms underlying human metabolic diseases. Here we collect functional phosphorylation events of 41 enzymes involved in yeast metabolism and demonstrate functional mechanisms and the application of this information in metabolic engineering. From a systems biology perspective, we...... describe the development of phosphoproteomics in yeast as well as approaches to analysing the phosphoproteomics data. Finally, we focus on integrated analyses with other omics data sets and genome-scale metabolic models. Despite the advances, future studies improving both experimental technologies...

Structured Performance Analysis for Component Based Systems

OpenAIRE

Salmi , N.; Moreaux , Patrice; Ioualalen , M.

2012-01-01

International audience; The Component Based System (CBS) paradigm is now largely used to design software systems. In addition, performance and behavioural analysis remains a required step for the design and the construction of efficient systems. This is especially the case of CBS, which involve interconnected components running concurrent processes. % This paper proposes a compositional method for modeling and structured performance analysis of CBS. Modeling is based on Stochastic Well-formed...

Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis

DEFF Research Database (Denmark)

Miller, Martin Lee; Brunak, Søren; Olsen, JV

2010-01-01

and phosphorylation sites were grouped according to their cell cycle kinetics and compared to publicly available messenger RNA microarray data. Most detected phosphorylation sites and more than 20% of all quantified proteins showed substantial regulation, mainly in mitotic cells. Kinase-motif analysis revealed global...

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.

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.

Sub-minute Phosphoregulation of Cell Cycle Systems during Plasmodium Gamete Formation

Directory of Open Access Journals (Sweden)

Brandon M. Invergo

2017-11-01

Full Text Available Summary: The transmission of malaria parasites to mosquitoes relies on the rapid induction of sexual reproduction upon their ingestion into a blood meal. Haploid female and male gametocytes become activated and emerge from their host cells, and the males enter the cell cycle to produce eight microgametes. The synchronized nature of gametogenesis allowed us to investigate phosphorylation signaling during its first minute in Plasmodium berghei via a high-resolution time course of the phosphoproteome. This revealed an unexpectedly broad response, with proteins related to distinct cell cycle events undergoing simultaneous phosphoregulation. We implicate several protein kinases in the process, and we validate our analyses on the plant-like calcium-dependent protein kinase 4 (CDPK4 and a homolog of serine/arginine-rich protein kinases (SRPK1. Mutants in these kinases displayed distinct phosphoproteomic disruptions, consistent with differences in their phenotypes. The results reveal the central role of protein phosphorylation in the atypical cell cycle regulation of a divergent eukaryote. : Invergo et al. measure a phosphoproteomic time course during a life cycle transition of a malarial parasite. They observed broad phosphoregulation on a sub-minute scale, including simultaneous regulation of replication- and mitosis-related proteins. Their analyses reveal conserved phosphorylation patterns, and they highlight functional roles of specific protein kinases during this process. Keywords: gametogenesis, proteomics, signal transduction, ARK2, CRK5

Gender-Based Analysis On-Line Dialogue. Final Report.

Science.gov (United States)

2001

An online dialogue on gender-based analysis (GBA) was held from February 15 to March 7, 2001. Invitations and a background paper titled "Why Gender-Based Analysis?" were sent to 350 women's organizations and individuals throughout Canada. Efforts were made to ensure that aboriginal and Metis women, visible minority women, and women with…

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...

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.

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)

An Evidence-Based Videotaped Running Biomechanics Analysis.

Science.gov (United States)

Souza, Richard B

2016-02-01

Running biomechanics play an important role in the development of injuries. Performing a running biomechanics analysis on injured runners can help to develop treatment strategies. This article provides a framework for a systematic video-based running biomechanics analysis plan based on the current evidence on running injuries, using 2-dimensional (2D) video and readily available tools. Fourteen measurements are proposed in this analysis plan from lateral and posterior video. Identifying simple 2D surrogates for 3D biomechanic variables of interest allows for widespread translation of best practices, and have the best opportunity to impact the highly prevalent problem of the injured runner. Copyright © 2016 Elsevier Inc. All rights reserved.

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…

Cash-Flow Analysis Base of the Company's Performance Evaluation

OpenAIRE

Radu Riana Iren; Mihalcea Lucean; Negoescu Gheorghe

2013-01-01

Analyses based on the study of financial flows allow coherent merge to study the financial equilibrium of the firm's performance. If static analysis to assess the financial imbalance at some point, but does not explain its evolution, in contrast, dynamic analysis highlights the evolution of financial imbalance, but does not indicate the extent of it. It follows that the two kinds of analysis are complementary and should be pursued simultaneously. Dynamic analysis is based on the concept of st...

Analysis and Design of Reinforced Concrete Structures With Spring Base Isolation

International Nuclear Information System (INIS)

Tun Myint Aung; Tin Tin Win, Nyan Myint Kyaw

2008-06-01

In the study, analysis and design of four storey reinforced concrete building and it's isolations which is located in seismic zone 4. Then comparison of analysis result between fixed base condition and isolated condition of the building due to multi direction earthquake motions such as horizontal and vertical earthquake. Firstaly, static analysis is used for fixed base condition due to gravity unfactored load to design the helical spring. Secondly spectrum analysis is only utilized for horizontal earthquake and time history analysis is used for both horizontal earthquake and vertical earthquake respectively. Finally, comparison of the analysis results as forces, displacements, drifts, accelerations and shear at various levels of building are presented. The static period of fixed base is 0.4 sec. According to the base isolated concept, base isolated period is lengthened to 0.8 sec, 1 sec and 1.2sec for design earthquake level. The results which are especially compared to base isolated (1.2 sec) and fixed base building show that the displacements of base isolated is more than fixed base building but other seismic response such as acceleration of base isolated is significantly reduced compared to fixed base as well as base isloated building has capacity for reducing of member force of the structure with fixed base building

SET mediates TCE-induced liver cell apoptosis through dephosphorylation and upregulation of nucleolin.

Science.gov (United States)

Ren, Xiaohu; Huang, Xinfeng; Yang, Xifei; Liu, Yungang; Liu, Wei; Huang, Haiyan; Wu, Desheng; Zou, Fei; Liu, Jianjun

2017-06-20

Trichloroethylene (TCE) is an occupational and environmental chemical that can cause severe hepatotoxicity. While our previous studies showed that the phosphatase inhibitor SET is a key mediator of TCE-induced liver cell apoptosis, the molecular mechanisms remain elusive. Using quantitative phosphoproteomic analysis, we report here that nucleolin is a SET-regulated phosphoprotein in human liver HL-7702 cells. Functional analysis suggested that SET promoted dephosphorylation of nucleolin, decreased its binding to its transcriptional activator, c-myc, and upregulated nucleolin expression in TCE-treated cells. Importantly, TCE-induced hepatocyte apoptosis was significantly attenuated when nucleolin was downregulated with specific siRNAs. These findings indicate that TCE may induce hepatocyte apoptosis via SET-mediated dephosphorylation and overexpression of nucleolin.

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...

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 ...

Data-base tools for enhanced analysis of TMX-U data

International Nuclear Information System (INIS)

Stewart, M.E.; Carter, M.R.; Casper, T.A.; Meyer, W.H.; Perkins, D.E.; Whitney, D.M.

1986-01-01

The authors use a commercial data-base software package to create several data-base products that enhance the ability of experimental physicists to analyze data from the TMX-U experiment. This software resides on a Dec-20 computer in M-Divisions's user service center (USC), where data can be analyzed separately from the main acquisition computers. When these data-base tools are combined with interactive data analysis programs, physicists can perform automated (batch-style) processing or interactive data analysis on the computers in the USC or on the supercomputers of the NMFECC, in addition to the normal processing done on the acquisition system. One data-base tool provides highly reduced data for searching and correlation analysis of several diagnostic signals for a single shot or many shots. A second data-base tool provides retrieval and storage of unreduced data for detailed analysis of one or more diagnostic signals. The authors report how these data-base tools form the core of an evolving off-line data-analysis environment on the USC computers

Application of Metric-based Software Reliability Analysis to Example Software

International Nuclear Information System (INIS)

Kim, Man Cheol; Smidts, Carol

2008-07-01

The software reliability of TELLERFAST ATM software is analyzed by using two metric-based software reliability analysis methods, a state transition diagram-based method and a test coverage-based method. The procedures for the software reliability analysis by using the two methods and the analysis results are provided in this report. It is found that the two methods have a relation of complementary cooperation, and therefore further researches on combining the two methods to reflect the benefit of the complementary cooperative effect to the software reliability analysis are recommended

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...

Trial-Based Functional Analysis Informs Treatment for Vocal Scripting.

Science.gov (United States)

Rispoli, Mandy; Brodhead, Matthew; Wolfe, Katie; Gregori, Emily

2018-05-01

Research on trial-based functional analysis has primarily focused on socially maintained challenging behaviors. However, procedural modifications may be necessary to clarify ambiguous assessment results. The purposes of this study were to evaluate the utility of iterative modifications to trial-based functional analysis on the identification of putative reinforcement and subsequent treatment for vocal scripting. For all participants, modifications to the trial-based functional analysis identified a primary function of automatic reinforcement. The structure of the trial-based format led to identification of social attention as an abolishing operation for vocal scripting. A noncontingent attention treatment was evaluated using withdrawal designs for each participant. This noncontingent attention treatment resulted in near zero levels of vocal scripting for all participants. Implications for research and practice are presented.

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.

BASE - 2nd generation software for microarray data management and analysis

Directory of Open Access Journals (Sweden)

Nordborg Nicklas

2009-10-01

Full Text Available Abstract Background Microarray experiments are increasing in size and samples are collected asynchronously over long time. Available data are re-analysed as more samples are hybridized. Systematic use of collected data requires tracking of biomaterials, array information, raw data, and assembly of annotations. To meet the information tracking and data analysis challenges in microarray experiments we reimplemented and improved BASE version 1.2. Results The new BASE presented in this report is a comprehensive annotable local microarray data repository and analysis application providing researchers with an efficient information management and analysis tool. The information management system tracks all material from biosource, via sample and through extraction and labelling to raw data and analysis. All items in BASE can be annotated and the annotations can be used as experimental factors in downstream analysis. BASE stores all microarray experiment related data regardless if analysis tools for specific techniques or data formats are readily available. The BASE team is committed to continue improving and extending BASE to make it usable for even more experimental setups and techniques, and we encourage other groups to target their specific needs leveraging on the infrastructure provided by BASE. Conclusion BASE is a comprehensive management application for information, data, and analysis of microarray experiments, available as free open source software at http://base.thep.lu.se under the terms of the GPLv3 license.

BASE--2nd generation software for microarray data management and analysis.

Science.gov (United States)

Vallon-Christersson, Johan; Nordborg, Nicklas; Svensson, Martin; Häkkinen, Jari

2009-10-12

Microarray experiments are increasing in size and samples are collected asynchronously over long time. Available data are re-analysed as more samples are hybridized. Systematic use of collected data requires tracking of biomaterials, array information, raw data, and assembly of annotations. To meet the information tracking and data analysis challenges in microarray experiments we reimplemented and improved BASE version 1.2. The new BASE presented in this report is a comprehensive annotable local microarray data repository and analysis application providing researchers with an efficient information management and analysis tool. The information management system tracks all material from biosource, via sample and through extraction and labelling to raw data and analysis. All items in BASE can be annotated and the annotations can be used as experimental factors in downstream analysis. BASE stores all microarray experiment related data regardless if analysis tools for specific techniques or data formats are readily available. The BASE team is committed to continue improving and extending BASE to make it usable for even more experimental setups and techniques, and we encourage other groups to target their specific needs leveraging on the infrastructure provided by BASE. BASE is a comprehensive management application for information, data, and analysis of microarray experiments, available as free open source software at http://base.thep.lu.se under the terms of the GPLv3 license.

Trojan detection model based on network behavior analysis

International Nuclear Information System (INIS)

Liu Junrong; Liu Baoxu; Wang Wenjin

2012-01-01

Based on the analysis of existing Trojan detection technology, this paper presents a Trojan detection model based on network behavior analysis. First of all, we abstract description of the Trojan network behavior, then according to certain rules to establish the characteristic behavior library, and then use the support vector machine algorithm to determine whether a Trojan invasion. Finally, through the intrusion detection experiments, shows that this model can effectively detect Trojans. (authors)

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.

Sequential elution from IMAC (SIMAC)

DEFF Research Database (Denmark)

Thingholm, Tine E.; Larsen, Martin R.

2016-01-01

Phosphoproteomics relies on methods for efficient purification and sequencing of phosphopeptides from highly complex biological systems, especially when using low amounts of starting material. Current methods for phosphopeptide enrichment, e.g., Immobilized Metal ion Affinity Chromatography and t...

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)

Web-Based Trainer for Electrical Circuit Analysis

Science.gov (United States)

Weyten, L.; Rombouts, P.; De Maeyer, J.

2009-01-01

A Web-based system for training electric circuit analysis is presented in this paper. It is centered on symbolic analysis techniques and it not only verifies the student's final answer, but it also tracks and coaches him/her through all steps of his/her reasoning path. The system mimics homework assignments, enhanced by immediate personalized…

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)

Molecular methods for the study of signal transduction in plants

KAUST Repository

Irving, Helen R.; Gehring, Christoph A

2013-01-01

as well as at the systems level where transcriptomics and particularly phosphoproteomics afford a window into complex biological responses. Here we review the role of the cyclic nucleotides cAMP and cGMP in plant signal transduction as well

Phosphorylation dynamics during early differentiation of human embryonic stem cells

NARCIS (Netherlands)

van Hoof, D.; Munoz, J.; Braam, S.R.; Pinkse, M.W.H.; Linding, R.; Heck, A.J.R.; Mummery, C.L.; Krijgsveld, J.

2009-01-01

Pluripotent stem cells self-renew indefinitely and possess characteristic protein-protein networks that remodel during differentiation. How this occurs is poorly understood. Using quantitative mass spectrometry, we analyzed the (phospho)proteome of human embryonic stem cells (hESCs) during

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

β-Blockers are widely used to prevent cardiac arrhythmias and to treat hypertension by inhibiting β-adrenergic receptors (βARs) and thus decreasing contractility and heart rate. βARs initiate phosphorylation-dependent signaling cascades, but only a small number of the target proteins are known. We...

Global proteomic profiling of phosphopeptides using electron transfer dissociation tandem mass spectrometry

DEFF Research Database (Denmark)

Molina, Henrik; Horn, David M; Tang, Ning

2007-01-01

Electron transfer dissociation (ETD) is a recently introduced mass spectrometric technique that provides a more comprehensive coverage of peptide sequences and posttranslational modifications. Here, we evaluated the use of ETD for a global phosphoproteome analysis. In all, we identified a total...... of 1,435 phosphorylation sites from human embryonic kidney 293T cells, of which 1,141 ( approximately 80%) were not previously described. A detailed comparison of ETD and collision-induced dissociation (CID) modes showed that ETD identified 60% more phosphopeptides than CID, with an average of 40% more...... fragment ions that facilitated localization of phosphorylation sites. Although our data indicate that ETD is superior to CID for phosphorylation analysis, the two methods can be effectively combined in alternating ETD and CID modes for a more comprehensive analysis. Combining ETD and CID, from this single...

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.

Systematic inference of functional phosphorylation events in yeast metabolism

DEFF Research Database (Denmark)

Chen, Yu; Wang, Yonghong; Nielsen, Jens

2017-01-01

Motivation: Protein phosphorylation is a post-translational modification that affects proteins by changing their structure and conformation in a rapid and reversible way, and it is an important mechanism for metabolic regulation in cells. Phosphoproteomics enables high-throughput identification o...

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....

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

System based practice: a concept analysis

Directory of Open Access Journals (Sweden)

SHAHRAM YAZDANI

2016-04-01

Full Text Available Introduction: Systems-Based Practice (SBP is one of the six competencies introduced by the ACGME for physicians to provide high quality of care and also the most challenging of them in performance, training, and evaluation of medical students. This concept analysis clarifies the concept of SBP by identifying its components to make it possible to differentiate it from other similar concepts. For proper training of SBP and to ensure these competencies in physicians, it is necessary to have an operational definition, and SBP’s components must be precisely defined in order to provide valid and reliable assessment tools. Methods: Walker & Avant’s approach to concept analysis was performed in eight stages: choosing a concept, determining the purpose of analysis, identifying all uses of the concept, defining attributes, identifying a model case, identifying borderline, related, and contrary cases, identifying antecedents and consequences, and defining empirical referents. Results: Based on the analysis undertaken, the attributes of SBP includes knowledge of the system, balanced decision between patients’ need and system goals, effective role playing in interprofessional health care team, system level of health advocacy, and acting for system improvement. System thinking and a functional system are antecedents and system goals are consequences. A case model, as well as border, and contrary cases of SBP, has been introduced. Conclusion: The identification of SBP attributes in this study contributes to the body of knowledge in SBP and reduces the ambiguity of this concept to make it possible for applying it in training of different medical specialties. Also, it would be possible to develop and use more precise tools to evaluate SBP competency by using empirical referents of the analysis.

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 a...... analysis based on tree{structured graphical models is a simple nonlinear method competitive with, and sometimes superior to, other well{known linear methods like those assuming mutual independence between variables and linear logistic regression.......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...

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.

P³DB 3.0: From plant phosphorylation sites to protein networks.

Science.gov (United States)

Yao, Qiuming; Ge, Huangyi; Wu, Shangquan; Zhang, Ning; Chen, Wei; Xu, Chunhui; Gao, Jianjiong; Thelen, Jay J; Xu, Dong

2014-01-01

In the past few years, the Plant Protein Phosphorylation Database (P(3)DB, http://p3db.org) has become one of the most significant in vivo data resources for studying plant phosphoproteomics. We have substantially updated P(3)DB with respect to format, new datasets and analytic tools. In the P(3)DB 3.0, there are altogether 47 923 phosphosites in 16 477 phosphoproteins curated across nine plant organisms from 32 studies, which have met our multiple quality standards for acquisition of in vivo phosphorylation site data. Centralized by these phosphorylation data, multiple related data and annotations are provided, including protein-protein interaction (PPI), gene ontology, protein tertiary structures, orthologous sequences, kinase/phosphatase classification and Kinase Client Assay (KiC Assay) data--all of which provides context for the phosphorylation event. In addition, P(3)DB 3.0 incorporates multiple network viewers for the above features, such as PPI network, kinase-substrate network, phosphatase-substrate network, and domain co-occurrence network to help study phosphorylation from a systems point of view. Furthermore, the new P(3)DB reflects a community-based design through which users can share datasets and automate data depository processes for publication purposes. Each of these new features supports the goal of making P(3)DB a comprehensive, systematic and interactive platform for phosphoproteomics research.

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.

Visibility Graph Based Time Series Analysis.

Directory of Open Access Journals (Sweden)

Mutua Stephen

Full Text Available 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.

Phosphoproteomics and targeted antitumor therapies

International Nuclear Information System (INIS)

Pelicci, P.G.

2009-01-01

About 35% of acute myeloid leukemias (AML) are characterized by the presence of a mutant form of the NPM protein. NPM capacity of preserving stability and function of Arf, a protein with an important role in tumor suppression, is lost in mutant NPM (NPMmut). The objective of our research project is to attempt to characterize the interaction between NPM wild-type (WT) or the leukemic mutant with Arf in order to restore Arf activity in cancer cells. Our initial experimental plan required large scale production of the proteins of interest and their use in biochemical assays. Unfortunately, we encountered a number of technical problems and were unable to produce good amount of purified full length recombinant Arf protein, due to the fact that this protein is high insoluble

Boolean network identification from perturbation time series data combining dynamics abstraction and logic programming.

Science.gov (United States)

Ostrowski, M; Paulevé, L; Schaub, T; Siegel, A; Guziolowski, C

2016-11-01

Boolean networks (and more general logic models) are useful frameworks to study signal transduction across multiple pathways. Logic models can be learned from a prior knowledge network structure and multiplex phosphoproteomics data. However, most efficient and scalable training methods focus on the comparison of two time-points and assume that the system has reached an early steady state. In this paper, we generalize such a learning procedure to take into account the time series traces of phosphoproteomics data in order to discriminate Boolean networks according to their transient dynamics. To that end, we identify a necessary condition that must be satisfied by the dynamics of a Boolean network to be consistent with a discretized time series trace. Based on this condition, we use Answer Set Programming to compute an over-approximation of the set of Boolean networks which fit best with experimental data and provide the corresponding encodings. Combined with model-checking approaches, we end up with a global learning algorithm. Our approach is able to learn logic models with a true positive rate higher than 78% in two case studies of mammalian signaling networks; for a larger case study, our method provides optimal answers after 7min of computation. We quantified the gain in our method predictions precision compared to learning approaches based on static data. Finally, as an application, our method proposes erroneous time-points in the time series data with respect to the optimal learned logic models. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Feature-Based Analysis of Plasma-Based Particle Acceleration Data

Energy Technology Data Exchange (ETDEWEB)

Rubel, Oliver [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Geddes, Cameron G. R. [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Chen, Min [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Cormier-Michel, Estelle [Tech-X Corp., Boulder, CO (United States); Bethel, E. Wes [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)

2014-02-01

Plasma-based particle accelerators can produce and sustain thousands of times stronger acceleration fields than conventional particle accelerators, providing a potential solution to the problem of the growing size and cost of conventional particle accelerators. To facilitate scientific knowledge discovery from the ever growing collections of accelerator simulation data generated by accelerator physicists to investigate next-generation plasma-based particle accelerator designs, we describe a novel approach for automatic detection and classification of particle beams and beam substructures due to temporal differences in the acceleration process, here called acceleration features. The automatic feature detection in combination with a novel visualization tool for fast, intuitive, query-based exploration of acceleration features enables an effective top-down data exploration process, starting from a high-level, feature-based view down to the level of individual particles. We describe the application of our analysis in practice to analyze simulations of single pulse and dual and triple colliding pulse accelerator designs, and to study the formation and evolution of particle beams, to compare substructures of a beam and to investigate transverse particle loss.

Molecular-based recursive partitioning analysis model for glioblastoma in the temozolomide era a correlative analysis based on nrg oncology RTOG 0525

NARCIS (Netherlands)

Bell, Erica Hlavin; Pugh, Stephanie L.; McElroy, Joseph P.; Gilbert, Mark R.; Mehta, Minesh; Klimowicz, Alexander C.; Magliocco, Anthony; Bredel, Markus; Robe, Pierre; Grosu, Anca L.; Stupp, Roger; Curran, Walter; Becker, Aline P.; Salavaggione, Andrea L.; Barnholtz-Sloan, Jill S.; Aldape, Kenneth; Blumenthal, Deborah T.; Brown, Paul D.; Glass, Jon; Souhami, Luis; Lee, R. Jeffrey; Brachman, David; Flickinger, John; Won, Minhee; Chakravarti, Arnab

2017-01-01

IMPORTANCE: There is a need for a more refined, molecularly based classification model for glioblastoma (GBM) in the temozolomide era. OBJECTIVE: To refine the existing clinically based recursive partitioning analysis (RPA) model by incorporating molecular variables. DESIGN, SETTING, AND

Phosphotyrosine biased enrichment of tryptic peptides from cancer cells by combining pY-MIP and TiO2 affinity resins

DEFF Research Database (Denmark)

Bllaci, Loreta; Torsetnes, Silje Bøen; Wierzbicka, Celina Katarzyna

2017-01-01

Protein phosphorylation at distinct tyrosine residues (pY) is essential for fast, specific and accurate signal transduction in cells. Enrichment of pY-containing peptides derived from phosphoproteins is commonly facilitated by use of immobilized anti-pY antibodies prior to phosphoproteomics analy...

Quantitative maps of protein phosphorylation sites across 14 different rat organs and tissues

DEFF Research Database (Denmark)

Lundby, Alicia; Secher, Anna; Lage, Kasper

2012-01-01

Deregulated cellular signalling is a common hallmark of disease, and delineating tissue phosphoproteomes is key to unravelling the underlying mechanisms. Here we present the broadest tissue catalogue of phosphoproteins to date, covering 31,480 phosphorylation sites on 7,280 proteins quantified ac...

Automatic Video-based Analysis of Human Motion

DEFF Research Database (Denmark)

Fihl, Preben

The human motion contains valuable information in many situations and people frequently perform an unconscious analysis of the motion of other people to understand their actions, intentions, and state of mind. An automatic analysis of human motion will facilitate many applications and thus has...... received great interest from both industry and research communities. The focus of this thesis is on video-based analysis of human motion and the thesis presents work within three overall topics, namely foreground segmentation, action recognition, and human pose estimation. Foreground segmentation is often...... the first important step in the analysis of human motion. By separating foreground from background the subsequent analysis can be focused and efficient. This thesis presents a robust background subtraction method that can be initialized with foreground objects in the scene and is capable of handling...

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.

Clinical proteomics: Current status, challenges, and future perspectives

Directory of Open Access Journals (Sweden)

Shyh-Horng Chiou

2011-01-01

Full Text Available This account will give an overview and evaluation of the current advances in mass spectrometry (MS-based proteomics platforms and technology. A general review of some background information concerning the application of these methods in the characterization of molecular sizes and related protein expression profiles associated with different types of cells under varied experimental conditions will be presented. It is intended to provide a concise and succinct overview to those clinical researchers first exposed to this foremost powerful methodology in modern life sciences of postgenomic era. Proteomic characterization using highly sophisticated and expensive instrumentation of MS has been used to characterize biological samples of complex protein mixtures with vastly different protein structure and composition. These systems are then used to highlight the versatility and potential of the MS-based proteomic strategies for facilitating protein expression analysis of various disease-related organisms or tissues of interest. Major MS-based strategies reviewed herein include (1 matrix-assisted laser desorption ionization-MS and electron-spray ionization proteomics; (2 one-dimensional or two-dimensional gel-based proteomics; (3 gel-free shotgun proteomics in conjunction with liquid chromatography/tandem MS; (4 Multiple reaction monitoring coupled tandem MS quantitative proteomics and; (5 Phosphoproteomics based on immobilized metal affinity chromatography and liquid chromatography-MS/MS.

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

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...

Protein expression based multimarker analysis of breast cancer samples

International Nuclear Information System (INIS)

Presson, Angela P; Horvath, Steve; Yoon, Nam K; Bagryanova, Lora; Mah, Vei; Alavi, Mohammad; Maresh, Erin L; Rajasekaran, Ayyappan K; Goodglick, Lee; Chia, David

2011-01-01

Tissue microarray (TMA) data are commonly used to validate the prognostic accuracy of tumor markers. For example, breast cancer TMA data have led to the identification of several promising prognostic markers of survival time. Several studies have shown that TMA data can also be used to cluster patients into clinically distinct groups. Here we use breast cancer TMA data to cluster patients into distinct prognostic groups. We apply weighted correlation network analysis (WGCNA) to TMA data consisting of 26 putative tumor biomarkers measured on 82 breast cancer patients. Based on this analysis we identify three groups of patients with low (5.4%), moderate (22%) and high (50%) mortality rates, respectively. We then develop a simple threshold rule using a subset of three markers (p53, Na-KATPase-β1, and TGF β receptor II) that can approximately define these mortality groups. We compare the results of this correlation network analysis with results from a standard Cox regression analysis. We find that the rule-based grouping variable (referred to as WGCNA*) is an independent predictor of survival time. While WGCNA* is based on protein measurements (TMA data), it validated in two independent Affymetrix microarray gene expression data (which measure mRNA abundance). We find that the WGCNA patient groups differed by 35% from mortality groups defined by a more conventional stepwise Cox regression analysis approach. We show that correlation network methods, which are primarily used to analyze the relationships between gene products, are also useful for analyzing the relationships between patients and for defining distinct patient groups based on TMA data. We identify a rule based on three tumor markers for predicting breast cancer survival outcomes

Benefits of Exergy-Based Analysis for Aerospace Engineering Applications—Part I

Directory of Open Access Journals (Sweden)

John H. Doty

2009-01-01

Full Text Available This paper compares the analysis of systems from two different perspectives: an energy-based focus and an exergy-based focus. A complex system was simply modeled as interacting thermodynamic systems to illustrate the differences in analysis methodologies and results. The energy-based analysis had combinations of calculated states that are infeasible. On the other hand, the exergy-based analyses only allow feasible states. More importantly, the exergy-based analyses provide clearer insight to the combination of operating conditions for optimum system-level performance. The results strongly suggest changing the analysis/design paradigm used in aerospace engineering from energy-based to exergy-based. This methodology shift is even more critical in exploratory research and development where previous experience may not be available to provide guidance. Although the models used herein may appear simplistic, the message is very powerful and extensible to higher-fidelity models: the 1st Law is only a necessary condition for design, whereas the 1st and 2nd Laws provide the sufficiency condition.

Similar words analysis based on POS-CBOW language model

Directory of Open Access Journals (Sweden)

Dongru RUAN

2015-10-01

Full Text Available Similar words analysis is one of the important aspects in the field of natural language processing, and it has important research and application values in text classification, machine translation and information recommendation. Focusing on the features of Sina Weibo's short text, this paper presents a language model named as POS-CBOW, which is a kind of continuous bag-of-words language model with the filtering layer and part-of-speech tagging layer. The proposed approach can adjust the word vectors' similarity according to the cosine similarity and the word vectors' part-of-speech metrics. It can also filter those similar words set on the base of the statistical analysis model. The experimental result shows that the similar words analysis algorithm based on the proposed POS-CBOW language model is better than that based on the traditional CBOW language model.

Cryptographic protocol security analysis based on bounded constructing algorithm

Institute of Scientific and Technical Information of China (English)

无

2006-01-01

An efficient approach to analyzing cryptographic protocols is to develop automatic analysis tools based on formal methods. However, the approach has encountered the high computational complexity problem due to reasons that participants of protocols are arbitrary, their message structures are complex and their executions are concurrent. We propose an efficient automatic verifying algorithm for analyzing cryptographic protocols based on the Cryptographic Protocol Algebra (CPA) model proposed recently, in which algebraic techniques are used to simplify the description of cryptographic protocols and their executions. Redundant states generated in the analysis processes are much reduced by introducing a new algebraic technique called Universal Polynomial Equation and the algorithm can be used to verify the correctness of protocols in the infinite states space. We have implemented an efficient automatic analysis tool for cryptographic protocols, called ACT-SPA, based on this algorithm, and used the tool to check more than 20 cryptographic protocols. The analysis results show that this tool is more efficient, and an attack instance not offered previously is checked by using this tool.

Web-Based Analysis for Decision Support Systems

African Journals Online (AJOL)

pc

2018-03-05

Mar 5, 2018 ... Faculty of Computing and Information Technology, King Abdulaziz University, Jeddah, SA ... impact of web-based analysis on DSSs and how it affects ... Internal users. ... and control of models, especially accounting, financial,.

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.

Feasibility and demonstration of a cloud-based RIID analysis system

Energy Technology Data Exchange (ETDEWEB)

Wright, Michael C., E-mail: wrightmc@ornl.gov [Oak Ridge National Laboratory, Oak Ridge, TN 37831 (United States); Hertz, Kristin L.; Johnson, William C. [Sandia National Laboratories, Livermore, CA 94551 (United States); Sword, Eric D.; Younkin, James R. [Oak Ridge National Laboratory, Oak Ridge, TN 37831 (United States); Sadler, Lorraine E. [Sandia National Laboratories, Livermore, CA 94551 (United States)

2015-06-01

A significant limitation in the operational utility of handheld and backpack radioisotope identifiers (RIIDs) is the inability of their onboard algorithms to accurately and reliably identify the isotopic sources of the measured gamma-ray energy spectrum. A possible solution is to move the spectral analysis computations to an external device, the cloud, where significantly greater capabilities are available. The implementation and demonstration of a prototype cloud-based RIID analysis system have shown this type of system to be feasible with currently available communication and computational technology. A system study has shown that the potential user community could derive significant benefits from an appropriately implemented cloud-based analysis system and has identified the design and operational characteristics required by the users and stakeholders for such a system. A general description of the hardware and software necessary to implement reliable cloud-based analysis, the value of the cloud expressed by the user community, and the aspects of the cloud implemented in the demonstrations are discussed. - Highlights: • A prototype cloud-based RIID analysis system was implemented and demonstrated. • A cloud-based system was shown to be feasible with currently available technology. • A system study identified the operational characteristics required by the users. • The system study showed that the user community could derive significant benefit. • An architecture was defined for field testing by users in relevant environments.

Feasibility and demonstration of a cloud-based RIID analysis system

International Nuclear Information System (INIS)

Wright, Michael C.; Hertz, Kristin L.; Johnson, William C.; Sword, Eric D.; Younkin, James R.; Sadler, Lorraine E.

2015-01-01

A significant limitation in the operational utility of handheld and backpack radioisotope identifiers (RIIDs) is the inability of their onboard algorithms to accurately and reliably identify the isotopic sources of the measured gamma-ray energy spectrum. A possible solution is to move the spectral analysis computations to an external device, the cloud, where significantly greater capabilities are available. The implementation and demonstration of a prototype cloud-based RIID analysis system have shown this type of system to be feasible with currently available communication and computational technology. A system study has shown that the potential user community could derive significant benefits from an appropriately implemented cloud-based analysis system and has identified the design and operational characteristics required by the users and stakeholders for such a system. A general description of the hardware and software necessary to implement reliable cloud-based analysis, the value of the cloud expressed by the user community, and the aspects of the cloud implemented in the demonstrations are discussed. - Highlights: • A prototype cloud-based RIID analysis system was implemented and demonstrated. • A cloud-based system was shown to be feasible with currently available technology. • A system study identified the operational characteristics required by the users. • The system study showed that the user community could derive significant benefit. • An architecture was defined for field testing by users in relevant environments

RESEARCH NOTE Genome-based exome-sequencing analysis ...

Indian Academy of Sciences (India)

Navya

2017-02-22

Feb 22, 2017 ... Genome-based exome-sequencing analysis identifies GYG1, DIS3L, DDRGK1 genes ... Cardiology Division, Department of Internal Medicine, Severance .... with p values of <0.05 byanalyzing differences in allele distribution.

[Electroencephalogram Feature Selection Based on Correlation Coefficient Analysis].

Science.gov (United States)

Zhou, Jinzhi; Tang, Xiaofang

2015-08-01

In order to improve the accuracy of classification with small amount of motor imagery training data on the development of brain-computer interface (BCD systems, we proposed an analyzing method to automatically select the characteristic parameters based on correlation coefficient analysis. Throughout the five sample data of dataset IV a from 2005 BCI Competition, we utilized short-time Fourier transform (STFT) and correlation coefficient calculation to reduce the number of primitive electroencephalogram dimension, then introduced feature extraction based on common spatial pattern (CSP) and classified by linear discriminant analysis (LDA). Simulation results showed that the average rate of classification accuracy could be improved by using correlation coefficient feature selection method than those without using this algorithm. Comparing with support vector machine (SVM) optimization features algorithm, the correlation coefficient analysis can lead better selection parameters to improve the accuracy of classification.

Systems biology approach identifies the kinase Csnk1a1 as a regulator of the DNA damage response in embryonic stem cells

DEFF Research Database (Denmark)

Carreras Puigvert, Jordi; von Stechow, Louise; Siddappa, Ramakrishnaiah

2013-01-01

screen targeting all kinases, phosphatases, and transcription factors with global transcriptomics and phosphoproteomics to map the DDR in mouse embryonic stem cells treated with the DNA cross-linker cisplatin. Networks derived from canonical pathways shared in all three data sets were implicated in DNA...

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....... A complex timber structure with a large number of failure modes is modelled with only a few dominant failure modes. First, a component based robustness analysis is performed based on the reliability indices of the remaining elements after the removal of selected critical elements. The robustness...... 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....

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.

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.

1001 Proteomes: a functional proteomics portal for the analysis of Arabidopsis thaliana accessions.

Science.gov (United States)

Joshi, Hiren J; Christiansen, Katy M; Fitz, Joffrey; Cao, Jun; Lipzen, Anna; Martin, Joel; Smith-Moritz, A Michelle; Pennacchio, Len A; Schackwitz, Wendy S; Weigel, Detlef; Heazlewood, Joshua L

2012-05-15

The sequencing of over a thousand natural strains of the model plant Arabidopsis thaliana is producing unparalleled information at the genetic level for plant researchers. To enable the rapid exploitation of these data for functional proteomics studies, we have created a resource for the visualization of protein information and proteomic datasets for sequenced natural strains of A. thaliana. The 1001 Proteomes portal can be used to visualize amino acid substitutions or non-synonymous single-nucleotide polymorphisms in individual proteins of A. thaliana based on the reference genome Col-0. We have used the available processed sequence information to analyze the conservation of known residues subject to protein phosphorylation among these natural strains. The substitution of amino acids in A. thaliana natural strains is heavily constrained and is likely a result of the conservation of functional attributes within proteins. At a practical level, we demonstrate that this information can be used to clarify ambiguously defined phosphorylation sites from phosphoproteomic studies. Protein sets of available natural variants are available for download to enable proteomic studies on these accessions. Together this information can be used to uncover the possible roles of specific amino acids in determining the structure and function of proteins in the model plant A. thaliana. An online portal to enable the community to exploit these data can be accessed at http://1001proteomes.masc-proteomics.org/

Traditional Mold Analysis Compared to a DNA-based Method of Mold Analysis with Applications in Asthmatics' Homes

Science.gov (United States)

Traditional environmental mold analysis is based-on microscopic observations and counting of mold structures collected from the air on a sticky surface or culturing of molds on growth media for identification and quantification. A DNA-based method of mold analysis called mol...

Identification of tyrosine-phosphorylated proteins associated with metastasis and functional analysis of FER in human hepatocellular carcinoma cells

International Nuclear Information System (INIS)

Li, Haiyu; Ren, Zhenggang; Kang, Xiaonan; Zhang, Lan; Li, Xuefei; Wang, Yan; Xue, Tongchun; Shen, Yuefang; Liu, Yinkun

2009-01-01

Aberrant activity of tyrosine-phosphorylated proteins is commonly associated with HCC metastasis. Cell signaling events driven by these proteins are implicated in numerous processes that alter cancer cell behavior. Exploring the activities and signaling pathways of these proteins in HCC metastasis may help in identifying new candidate molecules for HCC-targeted therapy. Hep3B (a nonmetastatic HCC cell line) and MHCC97H (a highly metastatic HCC cell line) were used in this study, and the tyrosine-phosphorylated proteins expressed in these cell lines were profiled by a phosphoproteomics technique based on LC-MS/MS. Protein-protein interaction and functional clustering analyses were performed to determine the activities of the identified proteins and the signaling pathways closely related to HCC metastasis. In both cell lines, a total of 247 phosphotyrosine (pTyr) proteins containing 281 pTyr sites were identified without any stimulation. The involvement of almost 30% of these in liver or liver cancer has not been reported previously. Biological process clustering analysis indicated that pTyr proteins involved in cell motility, migration, protein autophosphorylation, cell-cell communication, and antiapoptosis functions were overexpressed during metastasis. Pathway clustering analysis revealed that signaling pathways such as those involved in EGFR signaling, cytokine- and chemokine-mediated signal transduction, and the PI3K and JAK-STAT cascades were significantly activated during HCC metastasis. Moreover, noncanonical regulation of the JNK cascade might also provide new targets for HCC metastasis. After comparing the pTyr proteins that were differentially expressed during HCC cell metastasis, we selected FER, a nonreceptor tyrosine kinase, and validated its role in terms of both expression and function. The data confirmed that FER might play a critical role in the invasion and metastasis of HCC. The identification of pTyr proteins and signaling pathways associated

Correlation between arterial blood gas analysis and peripheral blood gas analysis in acid-base unbalance state

Directory of Open Access Journals (Sweden)

Hyun Lee Kim

2012-06-01

Full Text Available Acid-base unbalance is most common problem in severe ill patient, especially in condition of abnormal renal function state. Acid-base unbalances are respiratory acidosis, respiratory alkalosis, metabolic acidosis, and metabolic alkalosis. Metabolic acidosis is frequently appeared in clinical state. Arterial blood gas analysis is considered as a basic test to the intensive care unit patient and emergency state. Recently some researches were done, comparing with arterial blood gas analysis and venous blood gas analysis. Because of venous blood sampling is safer than arterial blood gas analysis, and beside not so different among them for detecting pH, pCO2, HCO3, except pO2 measuring. This research was done in emergency room, and for explaining no different between arterial blood gas analysis and peripheral blood gas analysis result in acid-base unbalance state patient. Especially in kidney functions decreased state. : The study was done from March, 2010 to January, 2011. The object was 89 peoples who came to emergency room for treating internal medicine problem. (Women 53, average age: 66.7±12.1 Then compare between arterial blood gas analysis and peripheral blood gas analysis. Result: The mean arterial minus venous difference for pH, pCO2, and bicarbonate was −0.0170, 2.6528, and 0.6124. Bland-Altman plot was done for predicting agreement of two groups, and the scale was pH −2.95 to 4.17, pCO2 −4.45 to 9.76, bicarbonate −2.95 to 4.16, in 95% relative. Conclusion: The peripheral blood gas pH, pCO2, bicarbonate level is almost same as arterial blood gas analysis results. And enough to measuring acid-base unbalance state, in absent of arterial blood testing.

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...m3 micrograms per cubic meter US United States USACE United States Army Corp of Engineers USC United States Code USCB United States Census Bureau...effects and annoyance in that very few flight operations and ground engine runs occur between 2200 hours and 0700 hours. BMPs include restricting the

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

African Journals Online (AJOL)

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 of ...

GaitaBase: Web-based repository system for gait analysis.

Science.gov (United States)

Tirosh, Oren; Baker, Richard; McGinley, Jenny

2010-02-01

The need to share gait analysis data to improve clinical decision support has been recognised since the early 1990s. GaitaBase has been established to provide a web-accessible repository system of gait analysis data to improve the sharing of data across local and international clinical and research community. It is used by several clinical and research groups across the world providing cross-group access permissions to retrieve and analyse the data. The system is useful for bench-marking and quality assurance, clinical consultation, and collaborative research. It has the capacity to increase the population sample size and improve the quality of 'normative' gait data. In addition the accumulated stored data may facilitate clinicians in comparing their own gait data with others, and give a valuable insight into how effective specific interventions have been for others. 2009 Elsevier Ltd. All rights reserved.

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...... 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......, 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....

The heat is on: thermodynamic analysis in fragment-based drug discovery

NARCIS (Netherlands)

Edink, E.S.; Jansen, C.J.W.; Leurs, R.; De Esch, I.J.

2010-01-01

Thermodynamic analysis provides access to the determinants of binding affinity, enthalpy and entropy. In fragment-based drug discovery (FBDD), thermodynamic analysis provides a powerful tool to discriminate fragments based on their potential for successful optimization. The thermodynamic data

Failure mode and effects analysis of software-based automation systems

International Nuclear Information System (INIS)

Haapanen, P.; Helminen, A.

2002-08-01

Failure mode and effects analysis (FMEA) is one of the well-known analysis methods having an established position in the traditional reliability analysis. The purpose of FMEA is to identify possible failure modes of the system components, evaluate their influences on system behaviour and propose proper countermeasures to suppress these effects. The generic nature of FMEA has enabled its wide use in various branches of industry reaching from business management to the design of spaceships. The popularity and diverse use of the analysis method has led to multiple interpretations, practices and standards presenting the same analysis method. FMEA is well understood at the systems and hardware levels, where the potential failure modes usually are known and the task is to analyse their effects on system behaviour. Nowadays, more and more system functions are realised on software level, which has aroused the urge to apply the FMEA methodology also on software based systems. Software failure modes generally are unknown - 'software modules do not fail, they only display incorrect behaviour' - and depend on dynamic behaviour of the application. These facts set special requirements on the FMEA of software based systems and make it difficult to realise. In this report the failure mode and effects analysis is studied for the use of reliability analysis of software-based systems. More precisely, the target system of FMEA is defined to be a safety-critical software-based automation application in a nuclear power plant, implemented on an industrial automation system platform. Through a literature study the report tries to clarify the intriguing questions related to the practical use of software failure mode and effects analysis. The study is a part of the research project 'Programmable Automation System Safety Integrity assessment (PASSI)', belonging to the Finnish Nuclear Safety Research Programme (FINNUS, 1999-2002). In the project various safety assessment methods and tools for

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 of th...

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...

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.

The analysis of the initiating events in thorium-based molten salt reactor

International Nuclear Information System (INIS)

Zuo Jiaxu; Song Wei; Jing Jianping; Zhang Chunming

2014-01-01

The initiation events analysis and evaluation were the beginning of nuclear safety analysis and probabilistic safety analysis, and it was the key points of the nuclear safety analysis. Currently, the initiation events analysis method and experiences both focused on water reactor, but no methods and theories for thorium-based molten salt reactor (TMSR). With TMSR's research and development in China, the initiation events analysis and evaluation was increasingly important. The research could be developed from the PWR analysis theories and methods. Based on the TMSR's design, the theories and methods of its initiation events analysis could be researched and developed. The initiation events lists and analysis methods of the two or three generation PWR, high-temperature gascooled reactor and sodium-cooled fast reactor were summarized. Based on the TMSR's design, its initiation events would be discussed and developed by the logical analysis. The analysis of TMSR's initiation events was preliminary studied and described. The research was important to clarify the events analysis rules, and useful to TMSR's designs and nuclear safety analysis. (authors)

Object-Based Image Analysis Beyond Remote Sensing - the Human Perspective

Science.gov (United States)

Blaschke, T.; Lang, S.; Tiede, D.; Papadakis, M.; Györi, A.

2016-06-01

We introduce a prototypical methodological framework for a place-based GIS-RS system for the spatial delineation of place while incorporating spatial analysis and mapping techniques using methods from different fields such as environmental psychology, geography, and computer science. The methodological lynchpin for this to happen - when aiming to delineate place in terms of objects - is object-based image analysis (OBIA).

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

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.

Fuzzy probability based fault tree analysis to propagate and quantify epistemic uncertainty

International Nuclear Information System (INIS)

Purba, Julwan Hendry; Sony Tjahyani, D.T.; Ekariansyah, Andi Sofrany; Tjahjono, Hendro

2015-01-01

Highlights: • Fuzzy probability based fault tree analysis is to evaluate epistemic uncertainty in fuzzy fault tree analysis. • Fuzzy probabilities represent likelihood occurrences of all events in a fault tree. • A fuzzy multiplication rule quantifies epistemic uncertainty of minimal cut sets. • A fuzzy complement rule estimate epistemic uncertainty of the top event. • The proposed FPFTA has successfully evaluated the U.S. Combustion Engineering RPS. - Abstract: A number of fuzzy fault tree analysis approaches, which integrate fuzzy concepts into the quantitative phase of conventional fault tree analysis, have been proposed to study reliabilities of engineering systems. Those new approaches apply expert judgments to overcome the limitation of the conventional fault tree analysis when basic events do not have probability distributions. Since expert judgments might come with epistemic uncertainty, it is important to quantify the overall uncertainties of the fuzzy fault tree analysis. Monte Carlo simulation is commonly used to quantify the overall uncertainties of conventional fault tree analysis. However, since Monte Carlo simulation is based on probability distribution, this technique is not appropriate for fuzzy fault tree analysis, which is based on fuzzy probabilities. The objective of this study is to develop a fuzzy probability based fault tree analysis to overcome the limitation of fuzzy fault tree analysis. To demonstrate the applicability of the proposed approach, a case study is performed and its results are then compared to the results analyzed by a conventional fault tree analysis. The results confirm that the proposed fuzzy probability based fault tree analysis is feasible to propagate and quantify epistemic uncertainties in fault tree analysis

Model-based gene set analysis for Bioconductor.

Science.gov (United States)

Bauer, Sebastian; Robinson, Peter N; Gagneur, Julien

2011-07-01

Gene Ontology and other forms of gene-category analysis play a major role in the evaluation of high-throughput experiments in molecular biology. Single-category enrichment analysis procedures such as Fisher's exact test tend to flag large numbers of redundant categories as significant, which can complicate interpretation. We have recently developed an approach called model-based gene set analysis (MGSA), that substantially reduces the number of redundant categories returned by the gene-category analysis. In this work, we present the Bioconductor package mgsa, which makes the MGSA algorithm available to users of the R language. Our package provides a simple and flexible application programming interface for applying the approach. The mgsa package has been made available as part of Bioconductor 2.8. It is released under the conditions of the Artistic license 2.0. peter.robinson@charite.de; julien.gagneur@embl.de.

Setting Standards for Medically-Based Running Analysis

Science.gov (United States)

Vincent, Heather K.; Herman, Daniel C.; Lear-Barnes, Leslie; Barnes, Robert; Chen, Cong; Greenberg, Scott; Vincent, Kevin R.

2015-01-01

Setting standards for medically based running analyses is necessary to ensure that runners receive a high-quality service from practitioners. Medical and training history, physical and functional tests, and motion analysis of running at self-selected and faster speeds are key features of a comprehensive analysis. Self-reported history and movement symmetry are critical factors that require follow-up therapy or long-term management. Pain or injury is typically the result of a functional deficit above or below the site along the kinematic chain. PMID:25014394

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.|info:eu-repo/dai/nl/224281216; Queiroz Feitosa, R.; van der Meer, F.D.|info:eu-repo/dai/nl/138940908; 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

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

Feasibility and demonstration of a cloud-based RIID analysis system

Science.gov (United States)

Wright, Michael C.; Hertz, Kristin L.; Johnson, William C.; Sword, Eric D.; Younkin, James R.; Sadler, Lorraine E.

2015-06-01

A significant limitation in the operational utility of handheld and backpack radioisotope identifiers (RIIDs) is the inability of their onboard algorithms to accurately and reliably identify the isotopic sources of the measured gamma-ray energy spectrum. A possible solution is to move the spectral analysis computations to an external device, the cloud, where significantly greater capabilities are available. The implementation and demonstration of a prototype cloud-based RIID analysis system have shown this type of system to be feasible with currently available communication and computational technology. A system study has shown that the potential user community could derive significant benefits from an appropriately implemented cloud-based analysis system and has identified the design and operational characteristics required by the users and stakeholders for such a system. A general description of the hardware and software necessary to implement reliable cloud-based analysis, the value of the cloud expressed by the user community, and the aspects of the cloud implemented in the demonstrations are discussed.

Developing a Self-Report-Based Sequential Analysis Method for Educational Technology Systems: A Process-Based Usability Evaluation

Science.gov (United States)

Lin, Yi-Chun; Hsieh, Ya-Hui; Hou, Huei-Tse

2015-01-01

The development of a usability evaluation method for educational systems or applications, called the self-report-based sequential analysis, is described herein. The method aims to extend the current practice by proposing self-report-based sequential analysis as a new usability method, which integrates the advantages of self-report in survey…

CASAS: Cancer Survival Analysis Suite, a web based application.

Science.gov (United States)

Rupji, Manali; Zhang, Xinyan; Kowalski, Jeanne

2017-01-01

We present CASAS, a shiny R based tool for interactive survival analysis and visualization of results. The tool provides a web-based one stop shop to perform the following types of survival analysis:  quantile, landmark and competing risks, in addition to standard survival analysis.  The interface makes it easy to perform such survival analyses and obtain results using the interactive Kaplan-Meier and cumulative incidence plots.  Univariate analysis can be performed on one or several user specified variable(s) simultaneously, the results of which are displayed in a single table that includes log rank p-values and hazard ratios along with their significance. For several quantile survival analyses from multiple cancer types, a single summary grid is constructed. The CASAS package has been implemented in R and is available via http://shinygispa.winship.emory.edu/CASAS/. The developmental repository is available at https://github.com/manalirupji/CASAS/.

Recent advances in nanopore-based nucleic acid analysis and sequencing

International Nuclear Information System (INIS)

Shi, Jidong; Fang, Ying; Hou, Junfeng

2016-01-01

Nanopore-based sequencing platforms are transforming the field of genomic science. This review (containing 116 references) highlights some recent progress on nanopore-based nucleic acid analysis and sequencing. These studies are classified into three categories, biological, solid-state, and hybrid nanopores, according to their nanoporous materials. We begin with a brief description of the translocation-based detection mechanism of nanopores. Next, specific examples are given in nanopore-based nucleic acid analysis and sequencing, with an emphasis on identifying strategies that can improve the resolution of nanopores. This review concludes with a discussion of future research directions that will advance the practical applications of nanopore technology. (author)

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.

Reconstruction and signal propagation analysis of the Syk signaling network in breast cancer cells.

Directory of Open Access Journals (Sweden)

Aurélien Naldi

2017-03-01

Full Text Available The ability to build in-depth cell signaling networks from vast experimental data is a key objective of computational biology. The spleen tyrosine kinase (Syk protein, a well-characterized key player in immune cell signaling, was surprisingly first shown by our group to exhibit an onco-suppressive function in mammary epithelial cells and corroborated by many other studies, but the molecular mechanisms of this function remain largely unsolved. Based on existing proteomic data, we report here the generation of an interaction-based network of signaling pathways controlled by Syk in breast cancer cells. Pathway enrichment of the Syk targets previously identified by quantitative phospho-proteomics indicated that Syk is engaged in cell adhesion, motility, growth and death. Using the components and interactions of these pathways, we bootstrapped the reconstruction of a comprehensive network covering Syk signaling in breast cancer cells. To generate in silico hypotheses on Syk signaling propagation, we developed a method allowing to rank paths between Syk and its targets. We first annotated the network according to experimental datasets. We then combined shortest path computation with random walk processes to estimate the importance of individual interactions and selected biologically relevant pathways in the network. Molecular and cell biology experiments allowed to distinguish candidate mechanisms that underlie the impact of Syk on the regulation of cortactin and ezrin, both involved in actin-mediated cell adhesion and motility. The Syk network was further completed with the results of our biological validation experiments. The resulting Syk signaling sub-networks can be explored via an online visualization platform.

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...

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...

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

KAUST Repository

Alqurashi, May M.

2013-01-01

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

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

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...

Knowledge-base for the new human reliability analysis method, A Technique for Human Error Analysis (ATHEANA)

International Nuclear Information System (INIS)

Cooper, S.E.; Wreathall, J.; Thompson, C.M., Drouin, M.; Bley, D.C.

1996-01-01

This paper describes the knowledge base for the application of the new human reliability analysis (HRA) method, a ''A Technique for Human Error Analysis'' (ATHEANA). Since application of ATHEANA requires the identification of previously unmodeled human failure events, especially errors of commission, and associated error-forcing contexts (i.e., combinations of plant conditions and performance shaping factors), this knowledge base is an essential aid for the HRA analyst

Time-resolved Global and Chromatin Proteomics during Herpes Simplex Virus Type 1 (HSV-1) Infection.

Science.gov (United States)

Kulej, Katarzyna; Avgousti, Daphne C; Sidoli, Simone; Herrmann, Christin; Della Fera, Ashley N; Kim, Eui Tae; Garcia, Benjamin A; Weitzman, Matthew D

2017-04-01

Herpes simplex virus (HSV-1) lytic infection results in global changes to the host cell proteome and the proteins associated with host chromatin. We present a system level characterization of proteome dynamics during infection by performing a multi-dimensional analysis during HSV-1 lytic infection of human foreskin fibroblast (HFF) cells. Our study includes identification and quantification of the host and viral proteomes, phosphoproteomes, chromatin bound proteomes and post-translational modifications (PTMs) on cellular histones during infection. We analyzed proteomes across six time points of virus infection (0, 3, 6, 9, 12 and 15 h post-infection) and clustered trends in abundance using fuzzy c-means. Globally, we accurately quantified more than 4000 proteins, 200 differently modified histone peptides and 9000 phosphorylation sites on cellular proteins. In addition, we identified 67 viral proteins and quantified 571 phosphorylation events (465 with high confidence site localization) on viral proteins, which is currently the most comprehensive map of HSV-1 phosphoproteome. We investigated chromatin bound proteins by proteomic analysis of the high-salt chromatin fraction and identified 510 proteins that were significantly different in abundance during infection. We found 53 histone marks significantly regulated during virus infection, including a steady increase of histone H3 acetylation (H3K9ac and H3K14ac). Our data provide a resource of unprecedented depth for human and viral proteome dynamics during infection. Collectively, our results indicate that the proteome composition of the chromatin of HFF cells is highly affected during HSV-1 infection, and that phosphorylation events are abundant on viral proteins. We propose that our epi-proteomics approach will prove to be important in the characterization of other model infectious systems that involve changes to chromatin composition. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Analysis of security protocols based on challenge-response

Institute of Scientific and Technical Information of China (English)

LUO JunZhou; YANG Ming

2007-01-01

Security protocol is specified as the procedure of challenge-response, which uses applied cryptography to confirm the existence of other principals and fulfill some data negotiation such as session keys. Most of the existing analysis methods,which either adopt theorem proving techniques such as state exploration or logic reasoning techniques such as authentication logic, face the conflicts between analysis power and operability. To solve the problem, a new efficient method is proposed that provides SSM semantics-based definition of secrecy and authentication goals and applies authentication logic as fundamental analysis techniques,in which secrecy analysis is split into two parts: Explicit-Information-Leakage and Implicit-Information-Leakage, and correspondence analysis is concluded as the analysis of the existence relationship of Strands and the agreement of Strand parameters. This new method owns both the power of the Strand Space Model and concision of authentication logic.

Heading in the right direction: thermodynamics-based network analysis and pathway engineering.

Science.gov (United States)

Ataman, Meric; Hatzimanikatis, Vassily

2015-12-01

Thermodynamics-based network analysis through the introduction of thermodynamic constraints in metabolic models allows a deeper analysis of metabolism and guides pathway engineering. The number and the areas of applications of thermodynamics-based network analysis methods have been increasing in the last ten years. We review recent applications of these methods and we identify the areas that such analysis can contribute significantly, and the needs for future developments. We find that organisms with multiple compartments and extremophiles present challenges for modeling and thermodynamics-based flux analysis. The evolution of current and new methods must also address the issues of the multiple alternatives in flux directionalities and the uncertainties and partial information from analytical methods. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

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.)

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…

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.

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

Macroalgae Analysis A National GIS-based Analysis of Macroalgae Production Potential Summary Report and Project Plan

Energy Technology Data Exchange (ETDEWEB)

Roesijadi, Guritno; Coleman, Andre M.; Judd, Chaeli; Van Cleve, Frances B.; Thom, Ronald M.; Buenau, Kate E.; Tagestad, Jerry D.; Wigmosta, Mark S.; Ward, Jeffrey A.

2011-12-01

The overall project objective is to conduct a strategic analysis to assess the state of macroalgae as a feedstock for biofuels production. The objective in FY11 is to develop a multi-year systematic national assessment to evaluate the U.S. potential for macroalgae production using a GIS-based assessment tool and biophysical growth model developed as part of these activities. The initial model development for both resource assessment and constraints was completed and applied to the demonstration areas. The model for macroalgal growth was extended to the EEZ off the East and West Coasts of the United States, and a plan to merge the findings for an initial composite assessment was developed. In parallel, an assessment of land-based, port, and offshore infrastructure needs based on published and grey literature was conducted. Major information gaps and challenges encountered during this analysis were identified. Also conducted was an analysis of the type of local, state, and federal requirements that pertain to permitting land-based facilities and nearshore/offshore culture operations

[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.

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…

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…

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…

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.…

Analysis of survival data with dependent censoring copula-based approaches

CERN Document Server

Emura, Takeshi

2018-01-01

This book introduces readers to copula-based statistical methods for analyzing survival data involving dependent censoring. Primarily focusing on likelihood-based methods performed under copula models, it is the first book solely devoted to the problem of dependent censoring. The book demonstrates the advantages of the copula-based methods in the context of medical research, especially with regard to cancer patients’ survival data. Needless to say, the statistical methods presented here can also be applied to many other branches of science, especially in reliability, where survival analysis plays an important role. The book can be used as a textbook for graduate coursework or a short course aimed at (bio-) statisticians. To deepen readers’ understanding of copula-based approaches, the book provides an accessible introduction to basic survival analysis and explains the mathematical foundations of copula-based survival models.

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.

Dataset from the global phosphoproteomic mapping of early mitotic exit in human cells

Directory of Open Access Journals (Sweden)

Samuel Rogers

2015-12-01

Full Text Available The presence or absence of a phosphorylation on a substrate at any particular point in time is a functional readout of the balance in activity between the regulatory kinase and the counteracting phosphatase. Understanding how stable or short-lived a phosphorylation site is required for fully appreciating the biological consequences of the phosphorylation. Our current understanding of kinases and their substrates is well established; however, the role phosphatases play is less understood. Therefore, we utilized a phosphatase dependent model of mitotic exit to identify potential substrates that are preferentially dephosphorylated. Using this method, we identified >16,000 phosphosites on >3300 unique proteins, and quantified the temporal phosphorylation changes that occur during early mitotic exit (McCloy et al., 2015 [1]. Furthermore, we annotated the majority of these phosphorylation sites with a high confidence upstream kinase using published, motif and prediction based methods. The results from this study have been deposited into the ProteomeXchange repository with identifier PXD001559. Here we provide additional analysis of this dataset; for each of the major mitotic kinases we identified motifs that correlated strongly with phosphorylation status. These motifs could be used to predict the stability of phosphorylated residues in proteins of interest, and help infer potential functional roles for uncharacterized phosphorylations. In addition, we provide validation at the single cell level that serine residues phosphorylated by Cdk are stable during phosphatase dependent mitotic exit. In summary, this unique dataset contains information on the temporal mitotic stability of thousands of phosphorylation sites regulated by dozens of kinases, and information on the potential preference that phosphatases have at both the protein and individual phosphosite level. The compellation of this data provides an invaluable resource for the wider research

Molecular methods for the study of signal transduction in plants

KAUST Repository

Irving, Helen R.

2013-09-03

Novel and improved analytical methods have led to a rapid increase in our understanding of the molecular mechanism underlying plant signal transduction. Progress has been made both at the level of single-component analysis and in vivo imaging as well as at the systems level where transcriptomics and particularly phosphoproteomics afford a window into complex biological responses. Here we review the role of the cyclic nucleotides cAMP and cGMP in plant signal transduction as well as the discovery and biochemical and biological characterization of an increasing number of complex multi-domain nucleotide cyclases that catalyze the synthesis of cAMP and cGMP from ATP and GTP, respectively. © Springer Science+Business Media New York 2013.

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.

Nonlinear multi-analysis of agent-based financial market dynamics by epidemic system

Science.gov (United States)

Lu, Yunfan; Wang, Jun; Niu, Hongli

2015-10-01

Based on the epidemic dynamical system, we construct a new agent-based financial time series model. In order to check and testify its rationality, we compare the statistical properties of the time series model with the real stock market indices, Shanghai Stock Exchange Composite Index and Shenzhen Stock Exchange Component Index. For analyzing the statistical properties, we combine the multi-parameter analysis with the tail distribution analysis, the modified rescaled range analysis, and the multifractal detrended fluctuation analysis. For a better perspective, the three-dimensional diagrams are used to present the analysis results. The empirical research in this paper indicates that the long-range dependence property and the multifractal phenomenon exist in the real returns and the proposed model. Therefore, the new agent-based financial model can recurrence some important features of real stock markets.

Breath analysis based on micropreconcentrator for early cancer diagnosis

Science.gov (United States)

Lee, Sang-Seok

2018-02-01

We are developing micropreconcentrators based on micro/nanotechnology to detect trace levels of volatile organic compound (VOC) gases contained in human and canine exhaled breath. The possibility of using exhaled VOC gases as biomarkers for various cancer diagnoses has been previously discussed. For early cancer diagnosis, detection of trace levels of VOC gas is indispensable. Using micropreconcentrators based on MEMS technology or nanotechnology is very promising for detection of VOC gas. A micropreconcentrator based breath analysis technique also has advantages from the viewpoints of cost performance and availability for various cancers diagnosis. In this paper, we introduce design, fabrication and evaluation results of our MEMS and nanotechnology based micropreconcentrators. In the MEMS based device, we propose a flower leaf type Si microstructure, and its shape and configuration are optimized quantitatively by finite element method simulation. The nanotechnology based micropreconcentrator consists of carbon nanotube (CNT) structures. As a result, we achieve ppb level VOC gas detection with our micropreconcentrators and usual gas chromatography system that can detect on the order of ppm VOC in gas samples. In performance evaluation, we also confirm that the CNT based micropreconcentrator shows 115 times better concentration ratio than that of the Si based micropreconcentrator. Moreover, we discuss a commercialization idea for new cancer diagnosis using breath analysis. Future work and preliminary clinical testing in dogs is also discussed.

Analysis, Simulation, and Verification of Knowledge-Based, Rule-Based, and Expert Systems

Science.gov (United States)

Hinchey, Mike; Rash, James; Erickson, John; Gracanin, Denis; Rouff, Chris

2010-01-01

Mathematically sound techniques are used to view a knowledge-based system (KBS) as a set of processes executing in parallel and being enabled in response to specific rules being fired. The set of processes can be manipulated, examined, analyzed, and used in a simulation. The tool that embodies this technology may warn developers of errors in their rules, but may also highlight rules (or sets of rules) in the system that are underspecified (or overspecified) and need to be corrected for the KBS to operate as intended. The rules embodied in a KBS specify the allowed situations, events, and/or results of the system they describe. In that sense, they provide a very abstract specification of a system. The system is implemented through the combination of the system specification together with an appropriate inference engine, independent of the algorithm used in that inference engine. Viewing the rule base as a major component of the specification, and choosing an appropriate specification notation to represent it, reveals how additional power can be derived from an approach to the knowledge-base system that involves analysis, simulation, and verification. This innovative approach requires no special knowledge of the rules, and allows a general approach where standardized analysis, verification, simulation, and model checking techniques can be applied to the KBS.

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.

[Concept analysis "Competency-based education"].

Science.gov (United States)

Loosli, Clarence

2016-03-01

Competency-based education (CBE) stands out at global level as the best educational practice. Indeed, CBE is supposed to improve the quality of care provided by newly graduated nurses. Yet, there is a dearth of knowledge in nursing literature regarding CBE concept's definition. CBE is implemented differently in each entity even inside the same discipline in a single country. What accounts for CBE in nursing education ? to clarify CBE concept meaning according to literature review in order to propose a definition. Wilson concept analysis method framed our literature review through two databases: CINHAL and ERIC. following the 11 Wilson techniques analysis, we identified CBE concept as a multidimensional concept clustering three dimensions : learning, teaching and assessment. nurses educators are accountable for providing performants newly graduated professional to the society. Schools should struggle for the visibility and the transparency of means they are using to accomplish their educational activities. This first attempt to understand CBE concept opens a matter of debate concerning further development and clarification of the concept. This first description of CBE concept is a step toward its identification and assessment.

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.

Matching biomedical ontologies based on formal concept analysis.

Science.gov (United States)

Zhao, Mengyi; Zhang, Songmao; Li, Weizhuo; Chen, Guowei

2018-03-19

The goal of ontology matching is to identify correspondences between entities from different yet overlapping ontologies so as to facilitate semantic integration, reuse and interoperability. As a well developed mathematical model for analyzing individuals and structuring concepts, Formal Concept Analysis (FCA) has been applied to ontology matching (OM) tasks since the beginning of OM research, whereas ontological knowledge exploited in FCA-based methods is limited. This motivates the study in this paper, i.e., to empower FCA with as much as ontological knowledge as possible for identifying mappings across ontologies. We propose a method based on Formal Concept Analysis to identify and validate mappings across ontologies, including one-to-one mappings, complex mappings and correspondences between object properties. Our method, called FCA-Map, incrementally generates a total of five types of formal contexts and extracts mappings from the lattices derived. First, the token-based formal context describes how class names, labels and synonyms share lexical tokens, leading to lexical mappings (anchors) across ontologies. Second, the relation-based formal context describes how classes are in taxonomic, partonomic and disjoint relationships with the anchors, leading to positive and negative structural evidence for validating the lexical matching. Third, the positive relation-based context can be used to discover structural mappings. Afterwards, the property-based formal context describes how object properties are used in axioms to connect anchor classes across ontologies, leading to property mappings. Last, the restriction-based formal context describes co-occurrence of classes across ontologies in anonymous ancestors of anchors, from which extended structural mappings and complex mappings can be identified. Evaluation on the Anatomy, the Large Biomedical Ontologies, and the Disease and Phenotype track of the 2016 Ontology Alignment Evaluation Initiative campaign

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.

An Analysis of Delay-based and Integrator-based Sequence Detectors for Grid-Connected Converters

DEFF Research Database (Denmark)

Khazraj, Hesam; Silva, Filipe Miguel Faria da; Bak, Claus Leth

2017-01-01

-signal cancellation operators are the main members of the delay-based sequence detectors. The aim of this paper is to provide a theoretical and experimental comparative study between integrator and delay based sequence detectors. The theoretical analysis is conducted based on the small-signal modelling......Detecting and separating positive and negative sequence components of the grid voltage or current is of vital importance in the control of grid-connected power converters, HVDC systems, etc. To this end, several techniques have been proposed in recent years. These techniques can be broadly...... classified into two main classes: The integrator-based techniques and Delay-based techniques. The complex-coefficient filter-based technique, dual second-order generalized integrator-based method, multiple reference frame approach are the main members of the integrator-based sequence detector and the delay...

Nondeducibility-Based Analysis of Cyber-Physical Systems

Science.gov (United States)

Gamage, Thoshitha; McMillin, Bruce

Controlling information flow in a cyber-physical system (CPS) is challenging because cyber domain decisions and actions manifest themselves as visible changes in the physical domain. This paper presents a nondeducibility-based observability analysis for CPSs. In many CPSs, the capacity of a low-level (LL) observer to deduce high-level (HL) actions ranges from limited to none. However, a collaborative set of observers strategically located in a network may be able to deduce all the HL actions. This paper models a distributed power electronics control device network using a simple DC circuit in order to understand the effect of multiple observers in a CPS. The analysis reveals that the number of observers required to deduce all the HL actions in a system increases linearly with the number of configurable units. A simple definition of nondeducibility based on the uniqueness of low-level projections is also presented. This definition is used to show that a system with two security domain levels could be considered “nondeducibility secure” if no unique LL projections exist.

Reverse-phase phosphoproteome analysis of signaling pathways induced by Rift valley fever virus in human small airway epithelial cells.

Directory of Open Access Journals (Sweden)

Taissia G Popova

Full Text Available Rift valley fever virus (RVFV infection is an emerging zoonotic disease endemic in many countries of sub-Saharan Africa and in Egypt. In this study we show that human small airway epithelial cells are highly susceptible to RVFV virulent strain ZH-501 and the attenuated strain MP-12. We used the reverse-phase protein arrays technology to identify phosphoprotein signaling pathways modulated during infection of cultured airway epithelium. ZH-501 infection induced activation of MAP kinases (p38, JNK and ERK and downstream transcriptional factors [STAT1 (Y701, ATF2 (T69/71, MSK1 (S360 and CREB (S133]. NF-κB phosphorylation was also increased. Activation of p53 (S15, S46 correlated with the increased levels of cleaved effector caspase-3, -6 and -7, indicating activation of the extrinsic apoptotic pathway. RVFV infection downregulated phosphorylation of a major anti-apoptotic regulator of survival pathways, AKT (S473, along with phosphorylation of FOX 01/03 (T24/31 which controls cell cycle arrest downstream from AKT. Consistent with this, the level of apoptosis inhibitor XIAP was decreased. However, the intrinsic apoptotic pathway marker, caspase-9, demonstrated only a marginal activation accompanied by an increased level of the inhibitor of apoptosome formation, HSP27. Concentration of the autophagy marker, LC3B, which often accompanies the pro-survival signaling, was decreased. Cumulatively, our analysis of RVFV infection in lung epithelium indicated a viral strategy directed toward the control of cell apoptosis through a number of transcriptional factors. Analyses of MP-12 titers in challenged cells in the presence of MAPK inhibitors indicated that activation of p38 represents a protective cell response while ERK activation controls viral replication.

Model-based security analysis of the German health card architecture.

Science.gov (United States)

Jürjens, J; Rumm, R

2008-01-01

Health-care information systems are particularly security-critical. In order to make these applications secure, the security analysis has to be an integral part of the system design and IT management process for such systems. This work presents the experiences and results from the security analysis of the system architecture of the German Health Card, by making use of an approach to model-based security engineering that is based on the UML extension UMLsec. The focus lies on the security mechanisms and security policies of the smart-card-based architecture which were analyzed using the UMLsec method and tools. Main results of the paper include a report on the employment of the UMLsec method in an industrial health information systems context as well as indications of its benefits and limitations. In particular, two potential security weaknesses were detected and countermeasures discussed. The results indicate that it can be feasible to apply a model-based security analysis using UMLsec to an industrial health information system like the German Health Card architecture, and that doing so can have concrete benefits (such as discovering potential weaknesses, and an increased confidence that no further vulnerabilities of the kind that were considered are present).

Knowledge-based low-level image analysis for computer vision systems

Science.gov (United States)

Dhawan, Atam P.; Baxi, Himanshu; Ranganath, M. V.

1988-01-01

Two algorithms for entry-level image analysis and preliminary segmentation are proposed which are flexible enough to incorporate local properties of the image. The first algorithm involves pyramid-based multiresolution processing and a strategy to define and use interlevel and intralevel link strengths. The second algorithm, which is designed for selected window processing, extracts regions adaptively using local histograms. The preliminary segmentation and a set of features are employed as the input to an efficient rule-based low-level analysis system, resulting in suboptimal meaningful segmentation.

IMPLEMENTATION OF GIS-BASED MULTICRITERIA DECISION ANALYSIS WITH VB IN ArcGIS

OpenAIRE

DERYA OZTURK; FATMAGUL BATUK

2011-01-01

This article focuses on the integration of multicriteria decision analysis (MCDA) and geographical information systems (GIS) and introduces a tool, GIS–MCDA, written in visual basic in ArcGIS for GIS-based MCDA. The GIS–MCDA deals with raster-based data sets and includes standardization, weighting and decision analysis methods, and sensitivity analysis. Simple additive weighting, weighted product method, technique for order preference by similarity to ideal solution, compromise programming, a...

Connotations of pixel-based scale effect in remote sensing and the modified fractal-based analysis method

Science.gov (United States)

Feng, Guixiang; Ming, Dongping; Wang, Min; Yang, Jianyu

2017-06-01

Scale problems are a major source of concern in the field of remote sensing. Since the remote sensing is a complex technology system, there is a lack of enough cognition on the connotation of scale and scale effect in remote sensing. Thus, this paper first introduces the connotations of pixel-based scale and summarizes the general understanding of pixel-based scale effect. Pixel-based scale effect analysis is essentially important for choosing the appropriate remote sensing data and the proper processing parameters. Fractal dimension is a useful measurement to analysis pixel-based scale. However in traditional fractal dimension calculation, the impact of spatial resolution is not considered, which leads that the scale effect change with spatial resolution can't be clearly reflected. Therefore, this paper proposes to use spatial resolution as the modified scale parameter of two fractal methods to further analyze the pixel-based scale effect. To verify the results of two modified methods (MFBM (Modified Windowed Fractal Brownian Motion Based on the Surface Area) and MDBM (Modified Windowed Double Blanket Method)); the existing scale effect analysis method (information entropy method) is used to evaluate. And six sub-regions of building areas and farmland areas were cut out from QuickBird images to be used as the experimental data. The results of the experiment show that both the fractal dimension and information entropy present the same trend with the decrease of spatial resolution, and some inflection points appear at the same feature scales. Further analysis shows that these feature scales (corresponding to the inflection points) are related to the actual sizes of the geo-object, which results in fewer mixed pixels in the image, and these inflection points are significantly indicative of the observed features. Therefore, the experiment results indicate that the modified fractal methods are effective to reflect the pixel-based scale effect existing in remote sensing

Frequency scanning-based stability analysis method for grid-connected inverter system

DEFF Research Database (Denmark)

Wang, Yanbo; Wang, Xiongfei; Blaabjerg, Frede

2017-01-01

This paper proposes a frequency scanning-based impedance analysis for stability assessment of grid-connected inverter system, which is able to perform stability assessment without using system mathematical models and inherit the superior feature of impedance-based stability criterion with conside......This paper proposes a frequency scanning-based impedance analysis for stability assessment of grid-connected inverter system, which is able to perform stability assessment without using system mathematical models and inherit the superior feature of impedance-based stability criterion...... with consideration of the inverter nonlinearities. Small current disturbance is injected into grid-connected inverter system in a particular frequency range, and the impedance is computed according to the harmonic-frequency response using Fourier analysis, and then the stability is predicted on the basis...... of the impedance stability criterion. The stability issues of grid-connected inverters with grid-current feedback and the converter-current feedback are addressed using the proposed method. The results obtained from simulation and experiments validate the effectiveness of the method. The frequency scanning...

Metrological analysis of a virtual flowmeter-based transducer for cryogenic helium

Energy Technology Data Exchange (ETDEWEB)

Arpaia, P., E-mail: pasquale.arpaia@unina.it [Department of Electrical Engineering and Information Technology, University of Napoli Federico II, Naples (Italy); Technology Department, European Organization for Nuclear Research (CERN), Geneva (Switzerland); Girone, M., E-mail: mario.girone@cern.ch [Technology Department, European Organization for Nuclear Research (CERN), Geneva (Switzerland); Department of Engineering, University of Sannio, Benevento (Italy); Liccardo, A., E-mail: annalisa.liccardo@unina.it [Department of Electrical Engineering and Information Technology, University of Napoli Federico II, Naples (Italy); Pezzetti, M., E-mail: marco.pezzetti@cern.ch [Technology Department, European Organization for Nuclear Research (CERN), Geneva (Switzerland); Piccinelli, F., E-mail: fabio.piccinelli@cern.ch [Department of Mechanical Engineering, University of Brescia, Brescia (Italy)

2015-12-15

The metrological performance of a virtual flowmeter-based transducer for monitoring helium under cryogenic conditions is assessed. At this aim, an uncertainty model of the transducer, mainly based on a valve model, exploiting finite-element approach, and a virtual flowmeter model, based on the Sereg-Schlumberger method, are presented. The models are validated experimentally on a case study for helium monitoring in cryogenic systems at the European Organization for Nuclear Research (CERN). The impact of uncertainty sources on the transducer metrological performance is assessed by a sensitivity analysis, based on statistical experiment design and analysis of variance. In this way, the uncertainty sources most influencing metrological performance of the transducer are singled out over the input range as a whole, at varying operating and setting conditions. This analysis turns out to be important for CERN cryogenics operation because the metrological design of the transducer is validated, and its components and working conditions with critical specifications for future improvements are identified.

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...

Research of second harmonic generation images based on texture analysis

Science.gov (United States)

Liu, Yao; Li, Yan; Gong, Haiming; Zhu, Xiaoqin; Huang, Zufang; Chen, Guannan

2014-09-01

Texture analysis plays a crucial role in identifying objects or regions of interest in an image. It has been applied to a variety of medical image processing, ranging from the detection of disease and the segmentation of specific anatomical structures, to differentiation between healthy and pathological tissues. Second harmonic generation (SHG) microscopy as a potential noninvasive tool for imaging biological tissues has been widely used in medicine, with reduced phototoxicity and photobleaching. In this paper, we clarified the principles of texture analysis including statistical, transform, structural and model-based methods and gave examples of its applications, reviewing studies of the technique. Moreover, we tried to apply texture analysis to the SHG images for the differentiation of human skin scar tissues. Texture analysis method based on local binary pattern (LBP) and wavelet transform was used to extract texture features of SHG images from collagen in normal and abnormal scars, and then the scar SHG images were classified into normal or abnormal ones. Compared with other texture analysis methods with respect to the receiver operating characteristic analysis, LBP combined with wavelet transform was demonstrated to achieve higher accuracy. It can provide a new way for clinical diagnosis of scar types. At last, future development of texture analysis in SHG images were discussed.

A GIS-based disaggregate spatial watershed analysis using RADAR data

International Nuclear Information System (INIS)

Al-Hamdan, M.

2002-01-01

Hydrology is the study of water in all its forms, origins, and destinations on the earth.This paper develops a novel modeling technique using a geographic information system (GIS) to facilitate watershed hydrological routing using RADAR data. The RADAR rainfall data, segmented to 4 km by 4 km blocks, divides the watershed into several sub basins which are modeled independently. A case study for the GIS-based disaggregate spatial watershed analysis using RADAR data is provided for South Fork Cowikee Creek near Batesville, Alabama. All the data necessary to complete the analysis is maintained in the ArcView GIS software. This paper concludes that the GIS-Based disaggregate spatial watershed analysis using RADAR data is a viable method to calculate hydrological routing for large watersheds. (author)

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

Wheeze sound analysis using computer-based techniques: a systematic review.

Science.gov (United States)

Ghulam Nabi, Fizza; Sundaraj, Kenneth; Chee Kiang, Lam; Palaniappan, Rajkumar; Sundaraj, Sebastian

2017-10-31

Wheezes are high pitched continuous respiratory acoustic sounds which are produced as a result of airway obstruction. Computer-based analyses of wheeze signals have been extensively used for parametric analysis, spectral analysis, identification of airway obstruction, feature extraction and diseases or pathology classification. While this area is currently an active field of research, the available literature has not yet been reviewed. This systematic review identified articles describing wheeze analyses using computer-based techniques on the SCOPUS, IEEE Xplore, ACM, PubMed and Springer and Elsevier electronic databases. After a set of selection criteria was applied, 41 articles were selected for detailed analysis. The findings reveal that 1) computerized wheeze analysis can be used for the identification of disease severity level or pathology, 2) further research is required to achieve acceptable rates of identification on the degree of airway obstruction with normal breathing, 3) analysis using combinations of features and on subgroups of the respiratory cycle has provided a pathway to classify various diseases or pathology that stem from airway obstruction.

Abnormal traffic flow data detection based on wavelet analysis

Directory of Open Access Journals (Sweden)

Xiao Qian

2016-01-01

Full Text Available In view of the traffic flow data of non-stationary, the abnormal data detection is difficult.proposed basing on the wavelet analysis and least squares method of abnormal traffic flow data detection in this paper.First using wavelet analysis to make the traffic flow data of high frequency and low frequency component and separation, and then, combined with least square method to find abnormal points in the reconstructed signal data.Wavelet analysis and least square method, the simulation results show that using wavelet analysis of abnormal traffic flow data detection, effectively reduce the detection results of misjudgment rate and false negative rate.

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.

Genome analysis and DNA marker-based characterisation of pathogenic trypanosomes

NARCIS (Netherlands)

Agbo, Edwin Chukwura

2003-01-01

The advances in genomics technologies and genome analysis methods that offer new leads for accelerating discovery of putative targets for developing overall control tools are reviewed in Chapter 1. In Chapter 2, a PCR typing method based on restriction fragment length polymorphism analysis of the

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.

The Arabidopsis co-expression tool (act): a WWW-based tool and database for microarray-based gene expression analysis

DEFF Research Database (Denmark)

Jen, C. H.; Manfield, I. W.; Michalopoulos, D. W.

2006-01-01

be examined using the novel clique finder tool to determine the sets of genes most likely to be regulated in a similar manner. In combination, these tools offer three levels of analysis: creation of correlation lists of co-expressed genes, refinement of these lists using two-dimensional scatter plots......We present a new WWW-based tool for plant gene analysis, the Arabidopsis Co-Expression Tool (act) , based on a large Arabidopsis thaliana microarray data set obtained from the Nottingham Arabidopsis Stock Centre. The co-expression analysis tool allows users to identify genes whose expression...

A methodology for developing high-integrity knowledge base using document analysis and ECPN matrix analysis with backward simulation

International Nuclear Information System (INIS)

Park, Joo Hyun

1999-02-01

When transitions occur in large systems such as nuclear power plants (NPPs) or industrial process plants, it is often difficult to diagnose them. Various computer-based operator-aiding systems have been developed in order to help operators diagnose the transitions of the plants. In procedures for developing knowledge base system like operator-aiding systems, the knowledge acquisition and the knowledge base verification are core activities. This dissertation describes a knowledge acquisition method and a knowledge base verification method for developing high-integrity knowledge base system of NPP expert systems. The knowledge acquisition is one of the most difficult and time-consuming activities in developing knowledge base systems. There are two kinds of knowledge acquisition methods in view of knowledge sources. One is an acquisition method from human expert. This method, however, is not adequate to acquire the knowledge of NPP expert systems because the number of experts is not sufficient. In this work, we propose a novel knowledge acquisition method through documents analysis. The knowledge base can be built correctly, rapidly, and partially automatically through this method. This method is especially useful when it is difficult to find domain experts. Reliability of knowledge base systems depends on the quality of their knowledge base. Petri Net has been used to verify knowledge bases due to their formal outputs. The methods using Petri Net however are difficult to apply to large and complex knowledge bases because the Net becomes very large and complex. Also, with Petri Net, it is difficult to find proper input patterns that make anomalies occur. In order to overcome this difficulty, in this work, the anomaly candidates detection methods are developed based on Extended CPN (ECPN) matrix analysis. This work also defines the backward simulation of CPN to find compact input patterns for anomaly detection, which starts simulation from the anomaly candidates

Uncertainty Analysis of Few Group Cross Sections Based on Generalized Perturbation Theory

International Nuclear Information System (INIS)

Han, Tae Young; Lee, Hyun Chul; Noh, Jae Man

2014-01-01

In this paper, the methodology of the sensitivity and uncertainty analysis code based on GPT was described and the preliminary verification calculations on the PMR200 pin cell problem were carried out. As a result, they are in a good agreement when compared with the results by TSUNAMI. From this study, it is expected that MUSAD code based on GPT can produce the uncertainty of the homogenized few group microscopic cross sections for a core simulator. For sensitivity and uncertainty analyses for general core responses, a two-step method is available and it utilizes the generalized perturbation theory (GPT) for homogenized few group cross sections in the first step and stochastic sampling method for general core responses in the second step. The uncertainty analysis procedure based on GPT in the first step needs the generalized adjoint solution from a cell or lattice code. For this, the generalized adjoint solver has been integrated into DeCART in our previous work. In this paper, MUSAD (Modues of Uncertainty and Sensitivity Analysis for DeCART) code based on the classical perturbation theory was expanded to the function of the sensitivity and uncertainty analysis for few group cross sections based on GPT. First, the uncertainty analysis method based on GPT was described and, in the next section, the preliminary results of the verification calculation on a VHTR pin cell problem were compared with the results by TSUNAMI of SCALE 6.1

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.

Prototype-based analysis of GAMA galaxy catalogue data

NARCIS (Netherlands)

Nolte, A.; Wang, L.; Biehl, M; Verleysen, Michel

2018-01-01

We present a prototype-based machine learning analysis of labeled galaxy catalogue data containing parameters from the Galaxy and Mass Assembly (GAMA) survey. Using both an unsupervised and supervised method, the Self-Organizing Map and Generalized Relevance Matrix Learning Vec- tor Quantization, we

Phylogenetic diversity analysis of Trichoderma species based on ...

African Journals Online (AJOL)

vi-4177/CSAU be assigned as the type strains of a species of genus Trichoderma based on phylogenetic tree analysis together with the 18S rRNA gene sequence search in Ribosomal Database Project, small subunit rRNA and large subunit ...

A methodology for strain-based fatigue reliability analysis

International Nuclear Information System (INIS)

Zhao, Y.X.

2000-01-01

A significant scatter of the cyclic stress-strain (CSS) responses should be noted for a nuclear reactor material, 1Cr18Ni9Ti pipe-weld metal. Existence of the scatter implies that a random cyclic strain applied history will be introduced under any of the loading modes even a deterministic loading history. A non-conservative evaluation might be given in the practice without considering the scatter. A methodology for strain-based fatigue reliability analysis, which has taken into account the scatter, is developed. The responses are approximately modeled by probability-based CSS curves of Ramberg-Osgood relation. The strain-life data are modeled, similarly, by probability-based strain-life curves of Coffin-Manson law. The reliability assessment is constructed by considering interference of the random fatigue strain applied and capacity histories. Probability density functions of the applied and capacity histories are analytically given. The methodology could be conveniently extrapolated to the case of deterministic CSS relation as the existent methods did. Non-conservative evaluation of the deterministic CSS relation and availability of present methodology have been indicated by an analysis of the material test results

New fatigue damage analysis of complex engineering components based on FEM

International Nuclear Information System (INIS)

Ott, W.

1987-05-01

A new type of fatigue damage analysis for multiaxial elastoplastic conditions based on a three-dimensional finite element analysis has been developed. The analysis includes the material model after Mroz. The fatigue life evaluation in the critical areas is based on plastic work at these locations. The proposed damage concept can be applied to arbitrary multiaxial stress-strain paths. For the evaluation of the damage cycles in terms of closed stress-strain hysteresis loops are not required. The damage is determined on the basis of uniaxial material data (stress-strain curve, life to crack iniation curve). (orig./HP) [de

Volumetric quantification of bone-implant contact using micro-computed tomography analysis based on region-based segmentation.

Science.gov (United States)

Kang, Sung-Won; Lee, Woo-Jin; Choi, Soon-Chul; Lee, Sam-Sun; Heo, Min-Suk; Huh, Kyung-Hoe; Kim, Tae-Il; Yi, Won-Jin

2015-03-01

We have developed a new method of segmenting the areas of absorbable implants and bone using region-based segmentation of micro-computed tomography (micro-CT) images, which allowed us to quantify volumetric bone-implant contact (VBIC) and volumetric absorption (VA). The simple threshold technique generally used in micro-CT analysis cannot be used to segment the areas of absorbable implants and bone. Instead, a region-based segmentation method, a region-labeling method, and subsequent morphological operations were successively applied to micro-CT images. The three-dimensional VBIC and VA of the absorbable implant were then calculated over the entire volume of the implant. Two-dimensional (2D) bone-implant contact (BIC) and bone area (BA) were also measured based on the conventional histomorphometric method. VA and VBIC increased significantly with as the healing period increased (pimplants using micro-CT analysis using a region-based segmentation method.

Map-based multicriteria analysis to support interactive land use allocation

NARCIS (Netherlands)

Arciniegas Lopez, G.A.; Janssen, R.; Omtzigt, A.Q.A.

2011-01-01

This article focuses on the use of map-based multicriteria analysis to develop a negotiation support tool for land use allocation. Spatial multicriteria analysis is used to make explicit trade-offs between objectives and to provide guidance and feedback on the land use changes negotiated by the

Qualitative safety analysis in accelerator based systems

International Nuclear Information System (INIS)

Sarkar, P.K.; Chowdhury, Lekha M.

2006-01-01

In recent developments connected to high energy and high current accelerators, the accelerator driven systems (ADS) and the Radioactive Ion Beam (RIB) facilities come in the forefront of application. For medical and industrial applications high current accelerators often need to be located in populated areas. These facilities pose significant radiological hazard during their operation and accidental situations. We have done a qualitative evaluation of radiological safety analysis using the probabilistic safety analysis (PSA) methods for accelerator-based systems. The major contribution to hazard comes from a target rupture scenario in both ADS and RIB facilities. Other significant contributors to hazard in the facilities are also discussed using fault tree and event tree methodologies. (author)

Sub-pattern based multi-manifold discriminant analysis for face recognition

Science.gov (United States)

Dai, Jiangyan; Guo, Changlu; Zhou, Wei; Shi, Yanjiao; Cong, Lin; Yi, Yugen

2018-04-01

In this paper, we present a Sub-pattern based Multi-manifold Discriminant Analysis (SpMMDA) algorithm for face recognition. Unlike existing Multi-manifold Discriminant Analysis (MMDA) approach which is based on holistic information of face image for recognition, SpMMDA operates on sub-images partitioned from the original face image and then extracts the discriminative local feature from the sub-images separately. Moreover, the structure information of different sub-images from the same face image is considered in the proposed method with the aim of further improve the recognition performance. Extensive experiments on three standard face databases (Extended YaleB, CMU PIE and AR) demonstrate that the proposed method is effective and outperforms some other sub-pattern based face recognition methods.

Synthesis of Enterprise and Value-Based Methods for Multiattribute Risk Analysis

International Nuclear Information System (INIS)

Kenley, C. Robert; Collins, John W.; Beck, John M.; Heydt, Harold J.; Garcia, Chad B.

2001-01-01

This paper describes a method for performing multiattribute decision analysis to prioritize ap-proaches to handling risks during the development and operation of complex socio-technical systems. The method combines risk categorization based on enterprise views, risk prioritization of the categories based on the Analytic Hierarchy Process (AHP), and more standard probability-consequence ratings schemes. We also apply value-based testing me-thods used in software development to prioritize risk-handling approaches. We describe a tool that synthesizes the methods and performs a multiattribute analysis of the technical and pro-grammatic risks on the Next Generation Nuclear Plant (NGNP) enterprise.

WebGimm: An integrated web-based platform for cluster analysis, functional analysis, and interactive visualization of results.

Science.gov (United States)

Joshi, Vineet K; Freudenberg, Johannes M; Hu, Zhen; Medvedovic, Mario

2011-01-17

Cluster analysis methods have been extensively researched, but the adoption of new methods is often hindered by technical barriers in their implementation and use. WebGimm is a free cluster analysis web-service, and an open source general purpose clustering web-server infrastructure designed to facilitate easy deployment of integrated cluster analysis servers based on clustering and functional annotation algorithms implemented in R. Integrated functional analyses and interactive browsing of both, clustering structure and functional annotations provides a complete analytical environment for cluster analysis and interpretation of results. The Java Web Start client-based interface is modeled after the familiar cluster/treeview packages making its use intuitive to a wide array of biomedical researchers. For biomedical researchers, WebGimm provides an avenue to access state of the art clustering procedures. For Bioinformatics methods developers, WebGimm offers a convenient avenue to deploy their newly developed clustering methods. WebGimm server, software and manuals can be freely accessed at http://ClusterAnalysis.org/.

Graph-Based Analysis of Nuclear Smuggling Data

International Nuclear Information System (INIS)

Cook, Diane; Holder, Larry; Thompson, Sandra E.; Whitney, Paul D.; Chilton, Lawrence

2009-01-01

Much of the data that is collected and analyzed today is structural, consisting not only of entities but also of relationships between the entities. As a result, analysis applications rely upon automated structural data mining approaches to find patterns and concepts of interest. This ability to analyze structural data has become a particular challenge in many security-related domains. In these domains, focusing on the relationships between entities in the data is critical to detect important underlying patterns. In this study we apply structural data mining techniques to automate analysis of nuclear smuggling data. In particular, we choose to model the data as a graph and use graph-based relational learning to identify patterns and concepts of interest in the data. In this paper, we identify the analysis questions that are of importance to security analysts and describe the knowledge representation and data mining approach that we adopt for this challenge. We analyze the results using the Russian nuclear smuggling event database.

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 g...

Structure and sensitivity analysis of individual-based predator–prey models

International Nuclear Information System (INIS)

Imron, Muhammad Ali; Gergs, Andre; Berger, Uta

2012-01-01

The expensive computational cost of sensitivity analyses has hampered the use of these techniques for analysing individual-based models in ecology. A relatively cheap computational cost, referred to as the Morris method, was chosen to assess the relative effects of all parameters on the model’s outputs and to gain insights into predator–prey systems. Structure and results of the sensitivity analysis of the Sumatran tiger model – the Panthera Population Persistence (PPP) and the Notonecta foraging model (NFM) – were compared. Both models are based on a general predation cycle and designed to understand the mechanisms behind the predator–prey interaction being considered. However, the models differ significantly in their complexity and the details of the processes involved. In the sensitivity analysis, parameters that directly contribute to the number of prey items killed were found to be most influential. These were the growth rate of prey and the hunting radius of tigers in the PPP model as well as attack rate parameters and encounter distance of backswimmers in the NFM model. Analysis of distances in both of the models revealed further similarities in the sensitivity of the two individual-based models. The findings highlight the applicability and importance of sensitivity analyses in general, and screening design methods in particular, during early development of ecological individual-based models. Comparison of model structures and sensitivity analyses provides a first step for the derivation of general rules in the design of predator–prey models for both practical conservation and conceptual understanding. - Highlights: ► Structure of predation processes is similar in tiger and backswimmer model. ► The two individual-based models (IBM) differ in space formulations. ► In both models foraging distance is among the sensitive parameters. ► Morris method is applicable for the sensitivity analysis even of complex IBMs.

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.

Fractal Dimension Analysis of Texture Formation of Whey Protein-Based Foods

Directory of Open Access Journals (Sweden)

Robi Andoyo

2018-01-01

Full Text Available Whey protein in the form of isolate or concentrate is widely used in food industries due to its functionality to form gel under certain condition and its nutritive value. Controlling or manipulating the formation of gel aggregates is used often to evaluate food texture. Many researchers made use of fractal analysis that provides the quantitative data (i.e., fractal dimension for fundamentally and rationally analyzing and designing whey protein-based food texture. This quantitative analysis is also done to better understand how the texture of whey protein-based food is formed. Two methods for fractal analysis were discussed in this review: image analysis (microscopy and rheology. These methods, however, have several limitations which greatly affect the accuracy of both fractal dimension values and types of aggregation obtained. This review therefore also discussed problem encountered and ways to reduce the potential errors during fractal analysis of each method.

Cognitive Task Analysis Based Training for Cyber Situation Awareness

OpenAIRE

Huang , Zequn; Shen , Chien-Chung; Doshi , Sheetal; Thomas , Nimmi; Duong , Ha

2015-01-01

Part 1: Innovative Methods; International audience; Cyber attacks have been increasing significantly in both number and complexity, prompting the need for better training of cyber defense analysts. To conduct effective training for cyber situation awareness, it becomes essential to design realistic training scenarios. In this paper, we present a Cognitive Task Analysis based approach to address this training need. The technique of Cognitive Task Analysis is to capture and represent knowledge ...

Estimating Driving Performance Based on EEG Spectrum Analysis

Directory of Open Access Journals (Sweden)

Jung Tzyy-Ping

2005-01-01

Full Text Available The growing number of traffic accidents in recent years has become a serious concern to society. Accidents caused by driver's drowsiness behind the steering wheel have a high fatality rate because of the marked decline in the driver's abilities of perception, recognition, and vehicle control abilities while sleepy. Preventing such accidents caused by drowsiness is highly desirable but requires techniques for continuously detecting, estimating, and predicting the level of alertness of drivers and delivering effective feedbacks to maintain their maximum performance. This paper proposes an EEG-based drowsiness estimation system that combines electroencephalogram (EEG log subband power spectrum, correlation analysis, principal component analysis, and linear regression models to indirectly estimate driver's drowsiness level in a virtual-reality-based driving simulator. Our results demonstrated that it is feasible to accurately estimate quantitatively driving performance, expressed as deviation between the center of the vehicle and the center of the cruising lane, in a realistic driving simulator.

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

Implementation and Optimization of GPU-Based Static State Security Analysis in Power Systems

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Yong Chen

2017-01-01

Full Text Available Static state security analysis (SSSA is one of the most important computations to check whether a power system is in normal and secure operating state. It is a challenge to satisfy real-time requirements with CPU-based concurrent methods due to the intensive computations. A sensitivity analysis-based method with Graphics processing unit (GPU is proposed for power systems, which can reduce calculation time by 40% compared to the execution on a 4-core CPU. The proposed method involves load flow analysis and sensitivity analysis. In load flow analysis, a multifrontal method for sparse LU factorization is explored on GPU through dynamic frontal task scheduling between CPU and GPU. The varying matrix operations during sensitivity analysis on GPU are highly optimized in this study. The results of performance evaluations show that the proposed GPU-based SSSA with optimized matrix operations can achieve a significant reduction in computation time.

Methodology for cost analysis of film-based and filmless portable chest systems

Science.gov (United States)

Melson, David L.; Gauvain, Karen M.; Beardslee, Brian M.; Kraitsik, Michael J.; Burton, Larry; Blaine, G. James; Brink, Gary S.

1996-05-01

Many studies analyzing the costs of film-based and filmless radiology have focused on multi- modality, hospital-wide solutions. Yet due to the enormous cost of converting an entire large radiology department or hospital to a filmless environment all at once, institutions often choose to eliminate film one area at a time. Narrowing the focus of cost-analysis may be useful in making such decisions. This presentation will outline a methodology for analyzing the cost per exam of film-based and filmless solutions for providing portable chest exams to Intensive Care Units (ICUs). The methodology, unlike most in the literature, is based on parallel data collection from existing filmless and film-based ICUs, and is currently being utilized at our institution. Direct costs, taken from the perspective of the hospital, for portable computed radiography chest exams in one filmless and two film-based ICUs are identified. The major cost components are labor, equipment, materials, and storage. Methods for gathering and analyzing each of the cost components are discussed, including FTE-based and time-based labor analysis, incorporation of equipment depreciation, lease, and maintenance costs, and estimation of materials costs. Extrapolation of data from three ICUs to model hypothetical, hospital-wide film-based and filmless ICU imaging systems is described. Performance of sensitivity analysis on the filmless model to assess the impact of anticipated reductions in specific labor, equipment, and archiving costs is detailed. A number of indirect costs, which are not explicitly included in the analysis, are identified and discussed.

Voxel-based analysis of the diffusion tensor

International Nuclear Information System (INIS)

Abe, Osamu; Takao, Hidemasa; Gonoi, Wataru; Sasaki, Hiroki; Murakami, Mizuho; Ohtomo, Kuni; Kabasawa, Hiroyuki; Kawaguchi, Hiroshi; Goto, Masami; Yamada, Haruyasu; Yamasue, Hidenori; Kasai, Kiyoto; Aoki, Shigeki

2010-01-01

Diffusion tensor imaging (DTI) has provided important insights into the neurobiological basis for normal development and aging and various disease processes in the central nervous system. The aim of this article is to review the current protocols for DTI acquisition and preprocessing and statistical testing for a voxelwise analysis of DTI, focused on statistical parametric mapping (SPM) and tract-based spatial statistics (TBSS). We tested the effects of distortion correction induced by gradient nonlinearity on fractional anisotropy (FA) maps or FA skeletons processed via two SPM-based methods (coregistration and FA template methods), or TBSS-based method, respectively. With two SPM-based methods, we found similar results in some points (e.g., significant FA elevation for uncorrected images in anterior-dominant white matter and for corrected images in bilateral middle cerebellar peduncles) and different results in other points (e.g., significantly larger FA for corrected images with coregistration method, but significantly smaller with FA template method in bilateral internal capsules, extending to corona radiata, and semioval centers). In contrast, there was no area with significant difference between uncorrected and corrected FA skeletons with TBSS-based method. The discrepancy among these results was not explained in full, but possible explanations were misregistration and smoothing for the SPM-based methods and insensitivity to FA changes outside the local centers of white matter bundles for TBSS-based method. (orig.)

Designing Experiments to Discriminate Families of Logic Models.

Science.gov (United States)

Videla, Santiago; Konokotina, Irina; Alexopoulos, Leonidas G; Saez-Rodriguez, Julio; Schaub, Torsten; Siegel, Anne; Guziolowski, Carito

2015-01-01

Logic models of signaling pathways are a promising way of building effective in silico functional models of a cell, in particular of signaling pathways. The automated learning of Boolean logic models describing signaling pathways can be achieved by training to phosphoproteomics data, which is particularly useful if it is measured upon different combinations of perturbations in a high-throughput fashion. However, in practice, the number and type of allowed perturbations are not exhaustive. Moreover, experimental data are unavoidably subjected to noise. As a result, the learning process results in a family of feasible logical networks rather than in a single model. This family is composed of logic models implementing different internal wirings for the system and therefore the predictions of experiments from this family may present a significant level of variability, and hence uncertainty. In this paper, we introduce a method based on Answer Set Programming to propose an optimal experimental design that aims to narrow down the variability (in terms of input-output behaviors) within families of logical models learned from experimental data. We study how the fitness with respect to the data can be improved after an optimal selection of signaling perturbations and how we learn optimal logic models with minimal number of experiments. The methods are applied on signaling pathways in human liver cells and phosphoproteomics experimental data. Using 25% of the experiments, we obtained logical models with fitness scores (mean square error) 15% close to the ones obtained using all experiments, illustrating the impact that our approach can have on the design of experiments for efficient model calibration.

Simulation-based training for nurses: Systematic review and meta-analysis.

Science.gov (United States)

Hegland, Pål A; Aarlie, Hege; Strømme, Hilde; Jamtvedt, Gro

2017-07-01

Simulation-based training is a widespread strategy to improve health-care quality. However, its effect on registered nurses has previously not been established in systematic reviews. The aim of this systematic review is to evaluate effect of simulation-based training on nurses' skills and knowledge. We searched CDSR, DARE, HTA, CENTRAL, CINAHL, MEDLINE, Embase, ERIC, and SveMed+ for randomised controlled trials (RCT) evaluating effect of simulation-based training among nurses. Searches were completed in December 2016. Two reviewers independently screened abstracts and full-text, extracted data, and assessed risk of bias. We compared simulation-based training to other learning strategies, high-fidelity simulation to other simulation strategies, and different organisation of simulation training. Data were analysed through meta-analysis and narrative syntheses. GRADE was used to assess the quality of evidence. Fifteen RCTs met the inclusion criteria. For the comparison of simulation-based training to other learning strategies on nurses' skills, six studies in the meta-analysis showed a significant, but small effect in favour of simulation (SMD -1.09, CI -1.72 to -0.47). There was large heterogeneity (I 2 85%). For the other comparisons, there was large between-study variation in results. The quality of evidence for all comparisons was graded as low. The effect of simulation-based training varies substantially between studies. Our meta-analysis showed a significant effect of simulation training compared to other learning strategies, but the quality of evidence was low indicating uncertainty. Other comparisons showed inconsistency in results. Based on our findings simulation training appears to be an effective strategy to improve nurses' skills, but further good-quality RCTs with adequate sample sizes are needed. Copyright © 2017 Elsevier Ltd. All rights reserved.

Feed particle size evaluation: conventional approach versus digital holography based image analysis

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Vittorio Dell’Orto

2010-01-01

Full Text Available The aim of this study was to evaluate the application of image analysis approach based on digital holography in defining particle size in comparison with the sieve shaker method (sieving method as reference method. For this purpose ground corn meal was analyzed by a sieve shaker Retsch VS 1000 and by image analysis approach based on digital holography. Particle size from digital holography were compared with results obtained by screen (sieving analysis for each of size classes by a cumulative distribution plot. Comparison between particle size values obtained by sieving method and image analysis indicated that values were comparable in term of particle size information, introducing a potential application for digital holography and image analysis in feed industry.

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...

Analysis of bi-directional piezoelectric-based converters for zero-voltage switching operation

DEFF Research Database (Denmark)

Ekhtiari, Marzieh; Zhang, Zhe; Andersen, Michael A. E.

2016-01-01

This paper deals with a thorough analysis of zerovoltage switching especially for bi-directional, inductorless, piezoelectric transformer-based switch-mode power supplies with a half-bridge topology. Practically, obtaining zero-voltage switching for all of the switches in a bi-directional piezoel......This paper deals with a thorough analysis of zerovoltage switching especially for bi-directional, inductorless, piezoelectric transformer-based switch-mode power supplies with a half-bridge topology. Practically, obtaining zero-voltage switching for all of the switches in a bi......-directional piezoelectric power converter is a difficult task. However, the analysis in this work will be convenient for overcoming this challenge. The analysis defines the zero-voltage region indicating the operating points whether or not soft switching can be met over the switching frequency and load range. For the first...... time, a comprehensive analysis is provided, which can be used as a design guideline for applying control techniques in order to drive switches in piezoelectric transformer-based converters. This study further conveys the proposed method to the region where all the switches can obtain soft switching...

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...

The analysis phase in development of knowledge-based systems

International Nuclear Information System (INIS)

Brooking, A.G.

1986-01-01

Over the past twenty years computer scientists have realized that, in order to produce reliable software that is easily modifiable, a proven methodology is required. Unlike conventional systems there is little knowledge of the life cycle of these knowledge-based systems. However, if the life cycle of conventional systems, it is not unreasonable to assume that analysis will come first. With respect to the analysis task there is an enormous difference in types of analysis. Conventional systems analysis is predominately concerned with what happens within the system. Typically, procedures will be noted in the way they relate to each other, the way data moves and changes within the system. There is often an example, on paper or machine, that can be observed

INNOVATION ANALYSIS BASED ON SCORES AT THE FIRM LEVEL

Directory of Open Access Journals (Sweden)

Cătălin George ALEXE

2014-04-01

Full Text Available Innovation analysis based on scores (Innovation Scorecard is a simple way to get a quick diagnosis on the potential of innovation of a firm in its intention to achieve the innovation capability. It aims to identify and remedy the deficient aspects related to innovation management being used as a measuring tool for the innovation initiatives over time within the innovation audit. The paper aims to present the advantages and disadvantages of using the method, and the three approaches developed over time. Therefore, the model proposed by the consulting firm Arthur D. Little in collaboration with the European Business School, Eckelmann's model and AGGB's local model are summarized and compared. At the end of the paper, several possible solutions are proposed to improve the way of analysis based on scores.

Developing group investigation-based book on numerical analysis to increase critical thinking student’s ability

Science.gov (United States)

Maharani, S.; Suprapto, E.

2018-03-01

Critical thinking is very important in Mathematics; it can make student more understanding mathematics concept. Critical thinking is also needed in numerical analysis. The Numerical analysis's book is not yet including critical thinking in them. This research aims to develop group investigation-based book on numerical analysis to increase critical thinking student’s ability, to know the quality of the group investigation-based book on numerical analysis is valid, practical, and effective. The research method is Research and Development (R&D) with the subject are 30 student college department of Mathematics education at Universitas PGRI Madiun. The development model used is 4-D modified to 3-D until the stage development. The type of data used is descriptive qualitative data. Instruments used are sheets of validation, test, and questionnaire. Development results indicate that group investigation-based book on numerical analysis in the category of valid a value 84.25%. Students response to the books very positive, so group investigation-based book on numerical analysis category practical, i.e., 86.00%. The use of group investigation-based book on numerical analysis has been meeting the completeness criteria classical learning that is 84.32 %. Based on research result of this study concluded that group investigation-based book on numerical analysis is feasible because it meets the criteria valid, practical, and effective. So, the book can be used by every mathematics academician. The next research can be observed that book based group investigation in other subjects.

Superior accuracy of model-based radiostereometric analysis for measurement of polyethylene wear

DEFF Research Database (Denmark)

Stilling, M; Kold, S; de Raedt, S

2012-01-01

The accuracy and precision of two new methods of model-based radiostereometric analysis (RSA) were hypothesised to be superior to a plain radiograph method in the assessment of polyethylene (PE) wear.......The accuracy and precision of two new methods of model-based radiostereometric analysis (RSA) were hypothesised to be superior to a plain radiograph method in the assessment of polyethylene (PE) wear....

Recurrence quantity analysis based on matrix eigenvalues

Science.gov (United States)

Yang, Pengbo; Shang, Pengjian

2018-06-01

Recurrence plots is a powerful tool for visualization and analysis of dynamical systems. Recurrence quantification analysis (RQA), based on point density and diagonal and vertical line structures in the recurrence plots, is considered to be alternative measures to quantify the complexity of dynamical systems. In this paper, we present a new measure based on recurrence matrix to quantify the dynamical properties of a given system. Matrix eigenvalues can reflect the basic characteristics of the complex systems, so we show the properties of the system by exploring the eigenvalues of the recurrence matrix. Considering that Shannon entropy has been defined as a complexity measure, we propose the definition of entropy of matrix eigenvalues (EOME) as a new RQA measure. We confirm that EOME can be used as a metric to quantify the behavior changes of the system. As a given dynamical system changes from a non-chaotic to a chaotic regime, the EOME will increase as well. The bigger EOME values imply higher complexity and lower predictability. We also study the effect of some factors on EOME,including data length, recurrence threshold, the embedding dimension, and additional noise. Finally, we demonstrate an application in physiology. The advantage of this measure lies in a high sensitivity and simple computation.

Geopolitical E-Analysis Based on E-Learning Content

Science.gov (United States)

Dinicu, Anca; Oancea, Romana

2017-01-01

In a world of great complexity, understanding the manner states act and react becomes more and more an intriguing quest due to the multiple relations of dependence and interdependence that characterize "the global puzzle". Within this context, an analysis based on a geopolitical approach becomes a very useful means used to determine not…

Automatic Online Lecture Highlighting Based on Multimedia Analysis

Science.gov (United States)

Che, Xiaoyin; Yang, Haojin; Meinel, Christoph

2018-01-01

Textbook highlighting is widely considered to be beneficial for students. In this paper, we propose a comprehensive solution to highlight the online lecture videos in both sentence- and segment-level, just as is done with paper books. The solution is based on automatic analysis of multimedia lecture materials, such as speeches, transcripts, and…

A Review of Pathway-Based Analysis Tools That Visualize Genetic Variants

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Elisa Cirillo

2017-11-01

Full Text Available Pathway analysis is a powerful method for data analysis in genomics, most often applied to gene expression analysis. It is also promising for single-nucleotide polymorphism (SNP data analysis, such as genome-wide association study data, because it allows the interpretation of variants with respect to the biological processes in which the affected genes and proteins are involved. Such analyses support an interactive evaluation of the possible effects of variations on function, regulation or interaction of gene products. Current pathway analysis software often does not support data visualization of variants in pathways as an alternate method to interpret genetic association results, and specific statistical methods for pathway analysis of SNP data are not combined with these visualization features. In this review, we first describe the visualization options of the tools that were identified by a literature review, in order to provide insight for improvements in this developing field. Tool evaluation was performed using a computational epistatic dataset of gene–gene interactions for obesity risk. Next, we report the necessity to include in these tools statistical methods designed for the pathway-based analysis with SNP data, expressly aiming to define features for more comprehensive pathway-based analysis tools. We conclude by recognizing that pathway analysis of genetic variations data requires a sophisticated combination of the most useful and informative visual aspects of the various tools evaluated.

Case Problems for Problem-Based Pedagogical Approaches: A Comparative Analysis

Science.gov (United States)

Dabbagh, Nada; Dass, Susan

2013-01-01

A comparative analysis of 51 case problems used in five problem-based pedagogical models was conducted to examine whether there are differences in their characteristics and the implications of such differences on the selection and generation of ill-structured case problems. The five pedagogical models were: situated learning, goal-based scenario,…

Train integrity detection risk analysis based on PRISM

Science.gov (United States)

Wen, Yuan

2018-04-01

GNSS based Train Integrity Monitoring System (TIMS) is an effective and low-cost detection scheme for train integrity detection. However, as an external auxiliary system of CTCS, GNSS may be influenced by external environments, such as uncertainty of wireless communication channels, which may lead to the failure of communication and positioning. In order to guarantee the reliability and safety of train operation, a risk analysis method of train integrity detection based on PRISM is proposed in this article. First, we analyze the risk factors (in GNSS communication process and the on-board communication process) and model them. Then, we evaluate the performance of the model in PRISM based on the field data. Finally, we discuss how these risk factors influence the train integrity detection process.

Use of knowledge based systems for rational reliability analysis based inspection and maintenance planning for offshore structures

International Nuclear Information System (INIS)

Tang, M.X.; Dharmavasan, S.; Peers, S.M.C.

1994-01-01

The structural integrity of fixed offshore platforms is ensured by periodic inspections. In the past, decisions made as to when, where and how to inspect have been made by engineers using rules-of-thumb and general planning heuristics. It is now hoped that more rational inspection and maintenance scheduling may be carried out by applying recently developed techniques based on structural reliability methods. However, one of the problems associated with a theoretical approach is that it is not always possible to incorporate all the constraints that are present in a practical situation. These constraints modify the decisions made for analysis data input and the interpretation of the analysis results. Knowledge based systems provide a mean of encapsulating several different forms of information and knowledge within a computer system and hence can overcome this problem. In this paper, a prototype system being developed for integrating reliability based analysis with other constraints for inspection scheduling will be described. In addition, the scheduling model and the algorithms to carry out the scheduling will be explained. Furthermore, implementation details are also given

iTemplate: A template-based eye movement data analysis approach.

Science.gov (United States)

Xiao, Naiqi G; Lee, Kang

2018-02-08

Current eye movement data analysis methods rely on defining areas of interest (AOIs). Due to the fact that AOIs are created and modified manually, variances in their size, shape, and location are unavoidable. These variances affect not only the consistency of the AOI definitions, but also the validity of the eye movement analyses based on the AOIs. To reduce the variances in AOI creation and modification and achieve a procedure to process eye movement data with high precision and efficiency, we propose a template-based eye movement data analysis method. Using a linear transformation algorithm, this method registers the eye movement data from each individual stimulus to a template. Thus, users only need to create one set of AOIs for the template in order to analyze eye movement data, rather than creating a unique set of AOIs for all individual stimuli. This change greatly reduces the error caused by the variance from manually created AOIs and boosts the efficiency of the data analysis. Furthermore, this method can help researchers prepare eye movement data for some advanced analysis approaches, such as iMap. We have developed software (iTemplate) with a graphic user interface to make this analysis method available to researchers.

Observability analysis for model-based fault detection and sensor selection in induction motors

International Nuclear Information System (INIS)

Nakhaeinejad, Mohsen; Bryant, Michael D

2011-01-01

Sensors in different types and configurations provide information on the dynamics of a system. For a specific task, the question is whether measurements have enough information or whether the sensor configuration can be changed to improve the performance or to reduce costs. Observability analysis may answer the questions. This paper presents a general algorithm of nonlinear observability analysis with application to model-based diagnostics and sensor selection in three-phase induction motors. A bond graph model of the motor is developed and verified with experiments. A nonlinear observability matrix based on Lie derivatives is obtained from state equations. An observability index based on the singular value decomposition of the observability matrix is obtained. Singular values and singular vectors are used to identify the most and least observable configurations of sensors and parameters. A complex step derivative technique is used in the calculation of Jacobians to improve the computational performance of the observability analysis. The proposed algorithm of observability analysis can be applied to any nonlinear system to select the best configuration of sensors for applications of model-based diagnostics, observer-based controller, or to determine the level of sensor redundancy. Observability analysis on induction motors provides various sensor configurations with corresponding observability indices. Results show the redundancy levels for different sensors, and provide a sensor selection guideline for model-based diagnostics, and for observer-based controllers. The results can also be used for sensor fault detection and to improve the reliability of the system by increasing the redundancy level in measurements

Volumetric quantification of bone-implant contact using micro-computed tomography analysis based on region-based segmentation

Energy Technology Data Exchange (ETDEWEB)

Kang, Sung Won; Lee, Woo Jin; Choi, Soon Chul; Lee, Sam Sun; Heo, Min Suk; Huh, Kyung Hoe; Kim, Tae Il; Yi, Won Ji [Dental Research Institute, School of Dentistry, Seoul National University, Seoul (Korea, Republic of)

2015-03-15

We have developed a new method of segmenting the areas of absorbable implants and bone using region-based segmentation of micro-computed tomography (micro-CT) images, which allowed us to quantify volumetric bone-implant contact (VBIC) and volumetric absorption (VA). The simple threshold technique generally used in micro-CT analysis cannot be used to segment the areas of absorbable implants and bone. Instead, a region-based segmentation method, a region-labeling method, and subsequent morphological operations were successively applied to micro-CT images. The three-dimensional VBIC and VA of the absorbable implant were then calculated over the entire volume of the implant. Two-dimensional (2D) bone-implant contact (BIC) and bone area (BA) were also measured based on the conventional histomorphometric method. VA and VBIC increased significantly with as the healing period increased (p<0.05). VBIC values were significantly correlated with VA values (p<0.05) and with 2D BIC values (p<0.05). It is possible to quantify VBIC and VA for absorbable implants using micro-CT analysis using a region-based segmentation method.

Volumetric quantification of bone-implant contact using micro-computed tomography analysis based on region-based segmentation

International Nuclear Information System (INIS)

Kang, Sung Won; Lee, Woo Jin; Choi, Soon Chul; Lee, Sam Sun; Heo, Min Suk; Huh, Kyung Hoe; Kim, Tae Il; Yi, Won Ji

2015-01-01

We have developed a new method of segmenting the areas of absorbable implants and bone using region-based segmentation of micro-computed tomography (micro-CT) images, which allowed us to quantify volumetric bone-implant contact (VBIC) and volumetric absorption (VA). The simple threshold technique generally used in micro-CT analysis cannot be used to segment the areas of absorbable implants and bone. Instead, a region-based segmentation method, a region-labeling method, and subsequent morphological operations were successively applied to micro-CT images. The three-dimensional VBIC and VA of the absorbable implant were then calculated over the entire volume of the implant. Two-dimensional (2D) bone-implant contact (BIC) and bone area (BA) were also measured based on the conventional histomorphometric method. VA and VBIC increased significantly with as the healing period increased (p<0.05). VBIC values were significantly correlated with VA values (p<0.05) and with 2D BIC values (p<0.05). It is possible to quantify VBIC and VA for absorbable implants using micro-CT analysis using a region-based segmentation method.

AR(p) -based detrended fluctuation analysis

Science.gov (United States)

Alvarez-Ramirez, J.; Rodriguez, E.

2018-07-01

Autoregressive models are commonly used for modeling time-series from nature, economics and finance. This work explored simple autoregressive AR(p) models to remove long-term trends in detrended fluctuation analysis (DFA). Crude oil prices and bitcoin exchange rate were considered, with the former corresponding to a mature market and the latter to an emergent market. Results showed that AR(p) -based DFA performs similar to traditional DFA. However, the former DFA provides information on stability of long-term trends, which is valuable for understanding and quantifying the dynamics of complex time series from financial systems.

Uniformity testing: assessment of a centralized web-based uniformity analysis system.

Science.gov (United States)

Klempa, Meaghan C

2011-06-01

Uniformity testing is performed daily to ensure adequate camera performance before clinical use. The aim of this study is to assess the reliability of Beth Israel Deaconess Medical Center's locally built, centralized, Web-based uniformity analysis system by examining the differences between manufacturer and Web-based National Electrical Manufacturers Association integral uniformity calculations measured in the useful field of view (FOV) and the central FOV. Manufacturer and Web-based integral uniformity calculations measured in the useful FOV and the central FOV were recorded over a 30-d period for 4 cameras from 3 different manufacturers. These data were then statistically analyzed. The differences between the uniformity calculations were computed, in addition to the means and the SDs of these differences for each head of each camera. There was a correlation between the manufacturer and Web-based integral uniformity calculations in the useful FOV and the central FOV over the 30-d period. The average differences between the manufacturer and Web-based useful FOV calculations ranged from -0.30 to 0.099, with SD ranging from 0.092 to 0.32. For the central FOV calculations, the average differences ranged from -0.163 to 0.055, with SD ranging from 0.074 to 0.24. Most of the uniformity calculations computed by this centralized Web-based uniformity analysis system are comparable to the manufacturers' calculations, suggesting that this system is reasonably reliable and effective. This finding is important because centralized Web-based uniformity analysis systems are advantageous in that they test camera performance in the same manner regardless of the manufacturer.

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

Paper-Plastic Hybrid Microfluidic Device for Smartphone-Based Colorimetric Analysis of Urine.

Science.gov (United States)

Jalal, Uddin M; Jin, Gyeong Jun; Shim, Joon S

2017-12-19

In this work, a disposable paper-plastic hybrid microfluidic lab-on-a-chip (LOC) has been developed and successfully applied for the colorimetric measurement of urine by the smartphone-based optical platform using a "UrineAnalysis" Android app. The developed device was cost-effectively implemented as a stand-alone hybrid LOC by incorporating the paper-based conventional reagent test strip inside the plastic-based LOC microchannel. The LOC device quantitatively investigated the small volume (40 μL) of urine analytes for the colorimetric reaction of glucose, protein, pH, and red blood cell (RBC) in integration with the finger-actuating micropump. On the basis of our experiments, the conventional urine strip showed large deviation as the reaction time goes by, because dipping the strip sensor in a bottle of urine could not control the reaction volume. By integrating the strip sensor in the LOC device for urine analysis, our device significantly improves the time-dependent inconstancy of the conventional dipstick-based urine strip, and the smartphone app used for image analysis enhances the visual assessment of the test strip, which is a major user concern for the colorimetric analysis in point-of-care (POC) applications. As a result, the user-friendly LOC, which is successfully implemented in a disposable format with the smartphone-based optical platform, may be applicable as an effective tool for rapid and qualitative POC urinalysis.

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...

Principle-based concept analysis: Caring in nursing education.

Science.gov (United States)

Salehian, Maryam; Heydari, Abbas; Aghebati, Nahid; Karimi Moonaghi, Hossein; Mazloom, Seyed Reza

2016-03-01

The aim of this principle-based concept analysis was to analyze caring in nursing education and to explain the current state of the science based on epistemologic, pragmatic, linguistic, and logical philosophical principles. A principle-based concept analysis method was used to analyze the nursing literature. The dataset included 46 English language studies, published from 2005 to 2014, and they were retrieved through PROQUEST, MEDLINE, CINAHL, ERIC, SCOPUS, and SID scientific databases. The key dimensions of the data were collected using a validated data-extraction sheet. The four principles of assessing pragmatic utility were used to analyze the data. The data were managed by using MAXQDA 10 software. The scientific literature that deals with caring in nursing education relies on implied meaning. Caring in nursing education refers to student-teacher interactions that are formed on the basis of human values and focused on the unique needs of the students (epistemological principle). The result of student-teacher interactions is the development of both the students and the teachers. Numerous applications of the concept of caring in nursing education are available in the literature (pragmatic principle). There is consistency in the meaning of the concept, as a central value of the faculty-student interaction (linguistic principle). Compared with other related concepts, such as "caring pedagogy," "value-based education," and "teaching excellence," caring in nursing education does not have exact and clear conceptual boundaries (logic principle). Caring in nursing education was identified as an approach to teaching and learning, and it is formed based on teacher-student interactions and sustainable human values. A greater understanding of the conceptual basis of caring in nursing education will improve the caring behaviors of teachers, create teaching-learning environments, and help experts in curriculum development.

Identifying novel glioma associated pathways based on systems biology level meta-analysis.

Science.gov (United States)

Hu, Yangfan; Li, Jinquan; Yan, Wenying; Chen, Jiajia; Li, Yin; Hu, Guang; Shen, Bairong

2013-01-01

With recent advances in microarray technology, including genomics, proteomics, and metabolomics, it brings a great challenge for integrating this "-omics" data to analysis complex disease. Glioma is an extremely aggressive and lethal form of brain tumor, and thus the study of the molecule mechanism underlying glioma remains very important. To date, most studies focus on detecting the differentially expressed genes in glioma. However, the meta-analysis for pathway analysis based on multiple microarray datasets has not been systematically pursued. In this study, we therefore developed a systems biology based approach by integrating three types of omics data to identify common pathways in glioma. Firstly, the meta-analysis has been performed to study the overlapping of signatures at different levels based on the microarray gene expression data of glioma. Among these gene expression datasets, 12 pathways were found in GeneGO database that shared by four stages. Then, microRNA expression profiles and ChIP-seq data were integrated for the further pathway enrichment analysis. As a result, we suggest 5 of these pathways could be served as putative pathways in glioma. Among them, the pathway of TGF-beta-dependent induction of EMT via SMAD is of particular importance. Our results demonstrate that the meta-analysis based on systems biology level provide a more useful approach to study the molecule mechanism of complex disease. The integration of different types of omics data, including gene expression microarrays, microRNA and ChIP-seq data, suggest some common pathways correlated with glioma. These findings will offer useful potential candidates for targeted therapeutic intervention of glioma.

Earthquake response analysis of a base isolated building

International Nuclear Information System (INIS)

Mazda, T.; Shiojiri, H.; Sawada, Y.; Harada, O.; Kawai, N.; Ontsuka, S.

1989-01-01

Recently, the seismic isolation has become one of the popular methods in the design of important structures or equipments against the earthquakes. However, it is desired to accumulate the demonstration data on reliability of seismically isolated structures and to establish the analysis methods of those structures. Based on the above recognition, the vibration tests of a base isolated building were carried out in Tsukuba Science City. After that, many earthquake records have been obtained at the building. In order to examine the validity of numerical models, earthquake response analyses have been executed by using both lumped mass model, and finite element model

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).

Numerical analysis of a polysilicon-based resistive memory device

KAUST Repository

Berco, Dan; Chand, Umesh

2018-01-01

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

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

KAUST Repository

Zhang, Yu; Xu, Ying; Arellano, Shawn M.; Xiao, Kang; Qian, Pei Yuan

2010-01-01

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

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

Directory of Open Access Journals (Sweden)

David Britton

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

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

Science.gov (United States)

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

2014-01-01

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

Static aeroelastic analysis including geometric nonlinearities based on reduced order model

Directory of Open Access Journals (Sweden)

Changchuan Xie

2017-04-01

Full Text Available This paper describes a method proposed for modeling large deflection of aircraft in nonlinear aeroelastic analysis by developing reduced order model (ROM. The method is applied for solving the static aeroelastic and static aeroelastic trim problems of flexible aircraft containing geometric nonlinearities; meanwhile, the non-planar effects of aerodynamics and follower force effect have been considered. ROMs are computational inexpensive mathematical representations compared to traditional nonlinear finite element method (FEM especially in aeroelastic solutions. The approach for structure modeling presented here is on the basis of combined modal/finite element (MFE method that characterizes the stiffness nonlinearities and we apply that structure modeling method as ROM to aeroelastic analysis. Moreover, the non-planar aerodynamic force is computed by the non-planar vortex lattice method (VLM. Structure and aerodynamics can be coupled with the surface spline method. The results show that both of the static aeroelastic analysis and trim analysis of aircraft based on structure ROM can achieve a good agreement compared to analysis based on the FEM and experimental result.

Ca analysis: an Excel based program for the analysis of intracellular calcium transients including multiple, simultaneous regression analysis.

Science.gov (United States)

Greensmith, David J

2014-01-01

Here I present an Excel based program for the analysis of intracellular Ca transients recorded using fluorescent indicators. The program can perform all the necessary steps which convert recorded raw voltage changes into meaningful physiological information. The program performs two fundamental processes. (1) It can prepare the raw signal by several methods. (2) It can then be used to analyze the prepared data to provide information such as absolute intracellular Ca levels. Also, the rates of change of Ca can be measured using multiple, simultaneous regression analysis. I demonstrate that this program performs equally well as commercially available software, but has numerous advantages, namely creating a simplified, self-contained analysis workflow. Copyright © 2013 The Author. Published by Elsevier Ireland Ltd.. All rights reserved.

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.

Frequency spectrum analysis of 252Cf neutron source based on LabVIEW

International Nuclear Information System (INIS)

Mi Deling; Li Pengcheng

2011-01-01

The frequency spectrum analysis of 252 Cf Neutron source is an extremely important method in nuclear stochastic signal processing. Focused on the special '0' and '1' structure of neutron pulse series, this paper proposes a fast-correlation algorithm to improve the computational rate of the spectrum analysis system. And the multi-core processor technology is employed as well as multi-threaded programming techniques of LabVIEW to construct frequency spectrum analysis system of 252 Cf neutron source based on LabVIEW. It not only obtains the auto-correlation and cross correlation results, but also auto-power spectrum,cross-power spectrum and ratio of spectral density. The results show that: analysis tools based on LabVIEW improve the fast auto-correlation and cross correlation code operating efficiency about by 25% to 35%, also verify the feasibility of using LabVIEW for spectrum analysis. (authors)

Pin-wise Reactor Analysis Based on the Generalized Equivalence Theory

Energy Technology Data Exchange (ETDEWEB)

Yu, Hwan Yeal; Heo, Woong; Kim, Yong Hee [KAIST, Daejeon (Korea, Republic of)

2016-05-15

In this paper, a pin-wise reactor analysis is performed based on the generalized equivalence theory. From the conventional fuel assembly lattice calculations, pin-wise 2-group cross sections and pin DFs are generated. Based on the numerical results on a small PWR benchmark, it is observed that the pin-wise core analysis provide quite accurate prediction on the effective multiplication factor and the peak pin power error is bounded by about 3% in peripheral fuel assemblies facing the baffle-reflector. Also, it was found that relatively large pin power errors occur along the interface between clearly different fuel assemblies. It is expected that the GET-based pin-by-pin core calculation can be further developed as an advanced method for reactor analysis via improving the group constants and discontinuity factors. Recently, high-fidelity multi-dimensional analysis tools are gaining more attention because of their accurate prediction of local parameters for core design and safety assessment. In terms of accuracy, direct whole-core transport is quite promising. However, it is clear that it is still very costly in terms of the computing time and memory requirements. Another possible solution is the pin-by-pin core analysis in which only small fuel pins are homogenized and the 3-D core analysis is still performed using a low-order operator such as the diffusion theory. In this paper, a pin-by-pin core analysis is performed using the hybrid CMFD (HCMFD) method. Hybrid CMFD is a new global-local iteration method that has been developed for efficient parallel calculation of pinby-pin heterogeneous core analysis. For the HCMFD method, the one-node CMFD scheme is combined with a local two-node CMFD method in a non-linear way. Since the SPH method is iterative and SPH factors are not direction dependent, it is clear that SPH method takes more computing cost and cannot take into account the different heterogeneity and transport effects at each pin interface. Unlike the SPH

Orthogonal Analysis Based Performance Optimization for Vertical Axis Wind Turbine

Directory of Open Access Journals (Sweden)

Lei Song

2016-01-01

Full Text Available Geometrical shape of a vertical axis wind turbine (VAWT is composed of multiple structural parameters. Since there are interactions among the structural parameters, traditional research approaches, which usually focus on one parameter at a time, cannot obtain performance of the wind turbine accurately. In order to exploit overall effect of a novel VAWT, we firstly use a single parameter optimization method to obtain optimal values of the structural parameters, respectively, by Computational Fluid Dynamics (CFD method; based on the results, we then use an orthogonal analysis method to investigate the influence of interactions of the structural parameters on performance of the wind turbine and to obtain optimization combination of the structural parameters considering the interactions. Results of analysis of variance indicate that interactions among the structural parameters have influence on performance of the wind turbine, and optimization results based on orthogonal analysis have higher wind energy utilization than that of traditional research approaches.

Non-Binary Protograph-Based LDPC Codes: Analysis,Enumerators and Designs

OpenAIRE

Sun, Yizeng

2013-01-01

Non-binary LDPC codes can outperform binary LDPC codes using sum-product algorithm with higher computation complexity. Non-binary LDPC codes based on protographs have the advantage of simple hardware architecture. In the first part of this thesis, we will use EXIT chart analysis to compute the thresholds of different protographs over GF(q). Based on threshold computation, some non-binary protograph-based LDPC codes are designed and their frame error rates are compared with binary LDPC codes. ...

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.

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...

Nondestructive elemental analysis of coins using accelerator-based thermal neutrons

International Nuclear Information System (INIS)

Khairi, F.Z.; Aksoy, A.; Al-Haddad, M.N.

2007-01-01

The accelerator-based thermal-neutrons activation analysis setup at KFUPM has an adequate thermal -neutron flux that can be advantageously used for the elemental analysis of a variety of samples including archeological ones. The thermal neutrons are derived from the moderation of fast neutrons from the D (d, n) He reaction which produces fast 2.5 MeV neutrons. A maximum thermals flux of about 2.5x10 n/m-s was achieved. For the purpose of determining the suitability of the set up for the analysis of contemporary and ancient coins, we carried out a feasibility study by irradiating a selected number of Saudi Arabian coins dating from 1958 to 1987 in the thermal-neutron flux. The induced gamma-ray activities were then counted using a HP-GMX detector coupled to a PC-based data acquisition and analysis system. The elements that were determined in the coins were copper (75%), nickel (around 25%) and manganese (<0.5%). Calibration curves were also established for these elements. The determined concentrations are in agreement with the data published by the Standard Catalogue of World Coins. (author)

Multiple Beta Spectrum Analysis Method Based on Spectrum Fitting

Energy Technology Data Exchange (ETDEWEB)

Lee, Uk Jae; Jung, Yun Song; Kim, Hee Reyoung [UNIST, Ulsan (Korea, Republic of)

2016-05-15

When the sample of several mixed radioactive nuclides is measured, it is difficult to divide each nuclide due to the overlapping of spectrums. For this reason, simple mathematical analysis method for spectrum analysis of the mixed beta ray source has been studied. However, existing research was in need of more accurate spectral analysis method as it has a problem of accuracy. The study will describe the contents of the separation methods of the mixed beta ray source through the analysis of the beta spectrum slope based on the curve fitting to resolve the existing problem. The fitting methods including It was understood that sum of sine fitting method was the best one of such proposed methods as Fourier, polynomial, Gaussian and sum of sine to obtain equation for distribution of mixed beta spectrum. It was shown to be the most appropriate for the analysis of the spectrum with various ratios of mixed nuclides. It was thought that this method could be applied to rapid spectrum analysis of the mixed beta ray source.

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. PMID:24623958

Content-based TV sports video retrieval using multimodal analysis

Science.gov (United States)

Yu, Yiqing; Liu, Huayong; Wang, Hongbin; Zhou, Dongru

2003-09-01

In this paper, we propose content-based video retrieval, which is a kind of retrieval by its semantical contents. Because video data is composed of multimodal information streams such as video, auditory and textual streams, we describe a strategy of using multimodal analysis for automatic parsing sports video. The paper first defines the basic structure of sports video database system, and then introduces a new approach that integrates visual stream analysis, speech recognition, speech signal processing and text extraction to realize video retrieval. The experimental results for TV sports video of football games indicate that the multimodal analysis is effective for video retrieval by quickly browsing tree-like video clips or inputting keywords within predefined domain.

Analysis of swimming performance: perceptions and practices of US-based swimming coaches.

Science.gov (United States)

Mooney, Robert; Corley, Gavin; Godfrey, Alan; Osborough, Conor; Newell, John; Quinlan, Leo Richard; ÓLaighin, Gearóid

2016-01-01

In elite swimming, a broad range of methods are used to assess performance, inform coaching practices and monitor athletic progression. The aim of this paper was to examine the performance analysis practices of swimming coaches and to explore the reasons behind the decisions that coaches take when analysing performance. Survey data were analysed from 298 Level 3 competitive swimming coaches (245 male, 53 female) based in the United States. Results were compiled to provide a generalised picture of practices and perceptions and to examine key emerging themes. It was found that a disparity exists between the importance swim coaches place on biomechanical analysis of swimming performance and the types of analyses that are actually conducted. Video-based methods are most frequently employed, with over 70% of coaches using these methods at least monthly, with analyses being mainly qualitative in nature rather than quantitative. Barriers to the more widespread use of quantitative biomechanical analysis in elite swimming environments were explored. Constraints include time, cost and availability of resources, but other factors such as sources of information on swimming performance and analysis and control over service provision are also discussed, with particular emphasis on video-based methods and emerging sensor-based technologies.

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.

Game-based digital interventions for depression therapy: a systematic review and meta-analysis.

Science.gov (United States)

Li, Jinhui; Theng, Yin-Leng; Foo, Schubert

2014-08-01

The aim of this study was to review the existing literature on game-based digital interventions for depression systematically and examine their effectiveness through a meta-analysis of randomized controlled trials (RCTs). Database searching was conducted using specific search terms and inclusion criteria. A standard meta-analysis was also conducted of available RCT studies with a random effects model. The standard mean difference (Cohen's d) was used to calculate the effect size of each study. Nineteen studies were included in the review, and 10 RCTs (eight studies) were included in the meta-analysis. Four types of game interventions-psycho-education and training, virtual reality exposure therapy, exercising, and entertainment-were identified, with various types of support delivered and populations targeted. The meta-analysis revealed a moderate effect size of the game interventions for depression therapy at posttreatment (d=-0.47 [95% CI -0.69 to -0.24]). A subgroup analysis showed that interventions based on psycho-education and training had a smaller effect than those based on the other forms, and that self-help interventions yielded better outcomes than supported interventions. A higher effect was achieved when a waiting list was used as the control. The review and meta-analysis support the effectiveness of game-based digital interventions for depression. More large-scale, high-quality RCT studies with sufficient long-term data for treatment evaluation are needed.

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)

Model-based Computer Aided Framework for Design of Process Monitoring and Analysis Systems

DEFF Research Database (Denmark)

Singh, Ravendra; Gernaey, Krist; Gani, Rafiqul

2009-01-01

In the manufacturing industry, for example, the pharmaceutical industry, a thorough understanding of the process is necessary in addition to a properly designed monitoring and analysis system (PAT system) to consistently obtain the desired end-product properties. A model-based computer....... The knowledge base provides the necessary information/data during the design of the PAT system while the model library generates additional or missing data needed for design and analysis. Optimization of the PAT system design is achieved in terms of product data analysis time and/or cost of monitoring equipment......-aided framework including the methods and tools through which the design of monitoring and analysis systems for product quality control can be generated, analyzed and/or validated, has been developed. Two important supporting tools developed as part of the framework are a knowledge base and a model library...

Likelihood-based Dynamic Factor Analysis for Measurement and Forecasting

NARCIS (Netherlands)

Jungbacker, B.M.J.P.; Koopman, S.J.

2015-01-01

We present new results for the likelihood-based analysis of the dynamic factor model. The latent factors are modelled by linear dynamic stochastic processes. The idiosyncratic disturbance series are specified as autoregressive processes with mutually correlated innovations. The new results lead to

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

Prediction Model of Machining Failure Trend Based on Large Data Analysis

Science.gov (United States)

Li, Jirong

2017-12-01

The mechanical processing has high complexity, strong coupling, a lot of control factors in the machining process, it is prone to failure, in order to improve the accuracy of fault detection of large mechanical equipment, research on fault trend prediction requires machining, machining fault trend prediction model based on fault data. The characteristics of data processing using genetic algorithm K mean clustering for machining, machining feature extraction which reflects the correlation dimension of fault, spectrum characteristics analysis of abnormal vibration of complex mechanical parts processing process, the extraction method of the abnormal vibration of complex mechanical parts processing process of multi-component spectral decomposition and empirical mode decomposition Hilbert based on feature extraction and the decomposition results, in order to establish the intelligent expert system for the data base, combined with large data analysis method to realize the machining of the Fault trend prediction. The simulation results show that this method of fault trend prediction of mechanical machining accuracy is better, the fault in the mechanical process accurate judgment ability, it has good application value analysis and fault diagnosis in the machining process.

Gold Nanoparticles-Based Barcode Analysis for Detection of Norepinephrine.

Science.gov (United States)

An, Jeung Hee; Lee, Kwon-Jai; Choi, Jeong-Woo

2016-02-01

Nanotechnology-based bio-barcode amplification analysis offers an innovative approach for detecting neurotransmitters. We evaluated the efficacy of this method for detecting norepinephrine in normal and oxidative-stress damaged dopaminergic cells. Our approach use a combination of DNA barcodes and bead-based immunoassays for detecting neurotransmitters with surface-enhanced Raman spectroscopy (SERS), and provides polymerase chain reaction (PCR)-like sensitivity. This method relies on magnetic Dynabeads containing antibodies and nanoparticles that are loaded both with DNA barcords and with antibodies that can sandwich the target protein captured by the Dynabead-bound antibodies. The aggregate sandwich structures are magnetically separated from the solution and treated to remove the conjugated barcode DNA. The DNA barcodes are then identified by SERS and PCR analysis. The concentration of norepinephrine in dopaminergic cells can be readily detected using the bio-barcode assay, which is a rapid, high-throughput screening tool for detecting neurotransmitters.

HDAT: web-based high-throughput screening data analysis tools

International Nuclear Information System (INIS)

Liu, Rong; Hassan, Taimur; Rallo, Robert; Cohen, Yoram

2013-01-01

The increasing utilization of high-throughput screening (HTS) in toxicity studies of engineered nano-materials (ENMs) requires tools for rapid and reliable processing and analyses of large HTS datasets. In order to meet this need, a web-based platform for HTS data analyses tools (HDAT) was developed that provides statistical methods suitable for ENM toxicity data. As a publicly available computational nanoinformatics infrastructure, HDAT provides different plate normalization methods, various HTS summarization statistics, self-organizing map (SOM)-based clustering analysis, and visualization of raw and processed data using both heat map and SOM. HDAT has been successfully used in a number of HTS studies of ENM toxicity, thereby enabling analysis of toxicity mechanisms and development of structure–activity relationships for ENM toxicity. The online approach afforded by HDAT should encourage standardization of and future advances in HTS as well as facilitate convenient inter-laboratory comparisons of HTS datasets. (paper)

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.

Model-Based Dependability Analysis of Physical Systems with Modelica

Directory of Open Access Journals (Sweden)

Andrea Tundis

2017-01-01

Full Text Available Modelica is an innovative, equation-based, and acausal language that allows modeling complex physical systems, which are made of mechanical, electrical, and electrotechnical components, and evaluates their design through simulation techniques. Unfortunately, the increasing complexity and accuracy of such physical systems require new, more powerful, and flexible tools and techniques for evaluating important system properties and, in particular, the dependability ones such as reliability, safety, and maintainability. In this context, the paper describes some extensions of the Modelica language to support the modeling of system requirements and their relationships. Such extensions enable the requirement verification analysis through native constructs in the Modelica language. Furthermore, they allow exporting a Modelica-based system design as a Bayesian Network in order to analyze its dependability by employing a probabilistic approach. The proposal is exemplified through a case study concerning the dependability analysis of a Tank System.

Creep Rupture Life Prediction Based on Analysis of Large Creep Deformation

Directory of Open Access Journals (Sweden)

YE Wenming

2016-08-01

Full Text Available A creep rupture life prediction method for high temperature component was proposed. The method was based on a true stress-strain elastoplastic creep constitutive model and the large deformation finite element analysis method. This method firstly used the high-temperature tensile stress-strain curve expressed by true stress and strain and the creep curve to build materials' elastoplastic and creep constitutive model respectively, then used the large deformation finite element method to calculate the deformation response of high temperature component under a given load curve, finally the creep rupture life was determined according to the change trend of the responsive curve.The method was verified by durable test of TC11 titanium alloy notched specimens under 500 ℃, and was compared with the three creep rupture life prediction methods based on the small deformation analysis. Results show that the proposed method can accurately predict the high temperature creep response and long-term life of TC11 notched specimens, and the accuracy is better than that of the methods based on the average effective stress of notch ligament, the bone point stress and the fracture strain of the key point, which are all based on small deformation finite element analysis.

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

Automated voxel-based analysis of brain perfusion SPECT for vasospasm after subarachnoid haemorrhage

International Nuclear Information System (INIS)

Iwabuchi, S.; Yokouchi, T.; Hayashi, M.; Kimura, H.; Tomiyama, A.; Hirata, Y.; Saito, N.; Harashina, J.; Nakayama, H.; Sato, K.; Aoki, K.; Samejima, H.; Ueda, M.; Terada, H.; Hamazaki, K.

2008-01-01

We evaluated regional cerebral blood flow (rCBF) during vasospasm after subarachnoid haemorrhage ISAH) using automated voxel-based analysis of brain perfusion single-photon emission computed tomography (SPELT). Brain perfusion SPECT was performed 7 to 10 days after onset of SAH. Automated voxel-based analysis of SPECT used a Z-score map that was calculated by comparing the patients data with a control database. In cases where computed tomography (CT) scans detected an ischemic region due to vasospasm, automated voxel-based analysis of brain perfusion SPECT revealed dramatically reduced rCBF (Z-score ≤ -4). No patients with mildly or moderately diminished rCBF (Z-score > -3) progressed to cerebral infarction. Some patients with a Z-score < -4 did not progress to cerebral infarction after active treatment with a angioplasty. Three-dimensional images provided detailed anatomical information and helped us to distinguish surgical sequelae from vasospasm. In conclusion, automated voxel-based analysis of brain perfusion SPECT using a Z-score map is helpful in evaluating decreased rCBF due to vasospasm. (author)

Discrimination based on HIV/AIDS status: A comparative analysis of ...

African Journals Online (AJOL)

Discrimination based on HIV/AIDS status: A comparative analysis of the Nigerian court's decision in Festus Odaife & Ors v Attorney General of the Federation & Ors with other Commonwealth jurisdictions.

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

Automics: an integrated platform for NMR-based metabonomics spectral processing and data analysis

Directory of Open Access Journals (Sweden)

Qu Lijia

2009-03-01

Full Text Available Abstract Background Spectral processing and post-experimental data analysis are the major tasks in NMR-based metabonomics studies. While there are commercial and free licensed software tools available to assist these tasks, researchers usually have to use multiple software packages for their studies because software packages generally focus on specific tasks. It would be beneficial to have a highly integrated platform, in which these tasks can be completed within one package. Moreover, with open source architecture, newly proposed algorithms or methods for spectral processing and data analysis can be implemented much more easily and accessed freely by the public. Results In this paper, we report an open source software tool, Automics, which is specifically designed for NMR-based metabonomics studies. Automics is a highly integrated platform that provides functions covering almost all the stages of NMR-based metabonomics studies. Automics provides high throughput automatic modules with most recently proposed algorithms and powerful manual modules for 1D NMR spectral processing. In addition to spectral processing functions, powerful features for data organization, data pre-processing, and data analysis have been implemented. Nine statistical methods can be applied to analyses including: feature selection (Fisher's criterion, data reduction (PCA, LDA, ULDA, unsupervised clustering (K-Mean and supervised regression and classification (PLS/PLS-DA, KNN, SIMCA, SVM. Moreover, Automics has a user-friendly graphical interface for visualizing NMR spectra and data analysis results. The functional ability of Automics is demonstrated with an analysis of a type 2 diabetes metabolic profile. Conclusion Automics facilitates high throughput 1D NMR spectral processing and high dimensional data analysis for NMR-based metabonomics applications. Using Automics, users can complete spectral processing and data analysis within one software package in most cases

Automics: an integrated platform for NMR-based metabonomics spectral processing and data analysis.

Science.gov (United States)

Wang, Tao; Shao, Kang; Chu, Qinying; Ren, Yanfei; Mu, Yiming; Qu, Lijia; He, Jie; Jin, Changwen; Xia, Bin

2009-03-16

Spectral processing and post-experimental data analysis are the major tasks in NMR-based metabonomics studies. While there are commercial and free licensed software tools available to assist these tasks, researchers usually have to use multiple software packages for their studies because software packages generally focus on specific tasks. It would be beneficial to have a highly integrated platform, in which these tasks can be completed within one package. Moreover, with open source architecture, newly proposed algorithms or methods for spectral processing and data analysis can be implemented much more easily and accessed freely by the public. In this paper, we report an open source software tool, Automics, which is specifically designed for NMR-based metabonomics studies. Automics is a highly integrated platform that provides functions covering almost all the stages of NMR-based metabonomics studies. Automics provides high throughput automatic modules with most recently proposed algorithms and powerful manual modules for 1D NMR spectral processing. In addition to spectral processing functions, powerful features for data organization, data pre-processing, and data analysis have been implemented. Nine statistical methods can be applied to analyses including: feature selection (Fisher's criterion), data reduction (PCA, LDA, ULDA), unsupervised clustering (K-Mean) and supervised regression and classification (PLS/PLS-DA, KNN, SIMCA, SVM). Moreover, Automics has a user-friendly graphical interface for visualizing NMR spectra and data analysis results. The functional ability of Automics is demonstrated with an analysis of a type 2 diabetes metabolic profile. Automics facilitates high throughput 1D NMR spectral processing and high dimensional data analysis for NMR-based metabonomics applications. Using Automics, users can complete spectral processing and data analysis within one software package in most cases. Moreover, with its open source architecture, interested

Resting-State Seed-Based Analysis: An Alternative to Task-Based Language fMRI and Its Laterality Index.

Science.gov (United States)

Smitha, K A; Arun, K M; Rajesh, P G; Thomas, B; Kesavadas, C

2017-06-01

Language is a cardinal function that makes human unique. Preservation of language function poses a great challenge for surgeons during resection. The aim of the study was to assess the efficacy of resting-state fMRI in the lateralization of language function in healthy subjects to permit its further testing in patients who are unable to perform task-based fMRI. Eighteen healthy right-handed volunteers were prospectively evaluated with resting-state fMRI and task-based fMRI to assess language networks. The laterality indices of Broca and Wernicke areas were calculated by using task-based fMRI via a voxel-value approach. We adopted seed-based resting-state fMRI connectivity analysis together with parameters such as amplitude of low-frequency fluctuation and fractional amplitude of low-frequency fluctuation (fALFF). Resting-state fMRI connectivity maps for language networks were obtained from Broca and Wernicke areas in both hemispheres. We performed correlation analysis between the laterality index and the z scores of functional connectivity, amplitude of low-frequency fluctuation, and fALFF. Pearson correlation analysis between signals obtained from the z score of fALFF and the laterality index yielded a correlation coefficient of 0.849 ( P laterality index yielded an R 2 value of 0.721, indicating that 72.1% of the variance in the laterality index of task-based fMRI could be predicted from the fALFF of resting-state fMRI. The present study demonstrates that fALFF can be used as an alternative to task-based fMRI for assessing language laterality. There was a strong positive correlation between the fALFF of the Broca area of resting-state fMRI with the laterality index of task-based fMRI. Furthermore, we demonstrated the efficacy of fALFF for predicting the laterality of task-based fMRI. © 2017 by American Journal of Neuroradiology.

Gating treatment delivery QA based on a surrogate motion analysis

International Nuclear Information System (INIS)

Chojnowski, J.; Simpson, E.

2011-01-01

Full text: To develop a methodology to estimate intrafractional target position error during a phase-based gated treatment. Westmead Cancer Care Centre is using respiratory correlated phase-based gated beam delivery in the treatment of lung cancer. The gating technique is managed by the Varian Real-time Position Management (RPM) system, version 1.7.5. A 6-dot block is placed on the abdomen of the patient and acts as a surrogate for the target motion. During a treatment session, the motion of the surrogate can be recorded by RPM application. Analysis of the surrogate motion file by in-house developed software allows the intrafractional error of the treatment session to be computed. To validate the computed error, a simple test that involves the introduction of deliberate errors is performed. Errors of up to 1.1 cm are introduced to a metal marker placed on a surrogate using the Varian Breathing Phantom. The moving marker was scanned in prospective mode using a GE Lightspeed 16 CT scanner. Using the CT images, a difference of the marker position with and without introduced errors is compared to the calculated errors based on the surrogate motion. The average and standard deviation of a difference between calculated target position errors and measured introduced artificial errors of the marker position is 0.02 cm and 0.07 cm respectively. Conclusion The calculated target positional error based on surrogate motion analysis provides a quantitative measure of intrafractional target positional errors during treatment. Routine QA for gated treatment using surrogate motion analysis is relatively quick and simple.

Visualization-based analysis of multiple response survey data

Science.gov (United States)

Timofeeva, Anastasiia

2017-11-01

During the survey, the respondents are often allowed to tick more than one answer option for a question. Analysis and visualization of such data have difficulties because of the need for processing multiple response variables. With standard representation such as pie and bar charts, information about the association between different answer options is lost. The author proposes a visualization approach for multiple response variables based on Venn diagrams. For a more informative representation with a large number of overlapping groups it is suggested to use similarity and association matrices. Some aggregate indicators of dissimilarity (similarity) are proposed based on the determinant of the similarity matrix and the maximum eigenvalue of association matrix. The application of the proposed approaches is well illustrated by the example of the analysis of advertising sources. Intersection of sets indicates that the same consumer audience is covered by several advertising sources. This information is very important for the allocation of the advertising budget. The differences between target groups in advertising sources are of interest. To identify such differences the hypothesis of homogeneity and independence are tested. Recent approach to the problem are briefly reviewed and compared. An alternative procedure is suggested. It is based on partition of a consumer audience into pairwise disjoint subsets and includes hypothesis testing of the difference between the population proportions. It turned out to be more suitable for the real problem being solved.

Distance Based Root Cause Analysis and Change Impact Analysis of Performance Regressions

Directory of Open Access Journals (Sweden)

Junzan Zhou

2015-01-01

Full Text Available Performance regression testing is applied to uncover both performance and functional problems of software releases. A performance problem revealed by performance testing can be high response time, low throughput, or even being out of service. Mature performance testing process helps systematically detect software performance problems. However, it is difficult to identify the root cause and evaluate the potential change impact. In this paper, we present an approach leveraging server side logs for identifying root causes of performance problems. Firstly, server side logs are used to recover call tree of each business transaction. We define a novel distance based metric computed from call trees for root cause analysis and apply inverted index from methods to business transactions for change impact analysis. Empirical studies show that our approach can effectively and efficiently help developers diagnose root cause of performance problems.

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

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.

FDTD technique based crosstalk analysis of bundled SWCNT interconnects

International Nuclear Information System (INIS)

Duksh, Yograj Singh; Kaushik, Brajesh Kumar; Agarwal, Rajendra P.

2015-01-01

The equivalent electrical circuit model of a bundled single-walled carbon nanotube based distributed RLC interconnects is employed for the crosstalk analysis. The accurate time domain analysis and crosstalk effect in the VLSI interconnect has emerged as an essential design criteria. This paper presents a brief description of the numerical method based finite difference time domain (FDTD) technique that is intended for estimation of voltages and currents on coupled transmission lines. For the FDTD implementation, the stability of the proposed model is strictly restricted by the Courant condition. This method is used for the estimation of crosstalk induced propagation delay and peak voltage in lossy RLC interconnects. Both functional and dynamic crosstalk effects are analyzed in the coupled transmission line. The effect of line resistance on crosstalk induced delay, and peak voltage under dynamic and functional crosstalk is also evaluated. The FDTD analysis and the SPICE simulations are carried out at 32 nm technology node for the global interconnects. It is observed that the analytical results obtained using the FDTD technique are in good agreement with the SPICE simulation results. The crosstalk induced delay, propagation delay, and peak voltage obtained using the FDTD technique shows average errors of 4.9%, 3.4% and 0.46%, respectively, in comparison to SPICE. (paper)

From the Analysis of Work-Processes to Designing Competence-Based Occupational Standards and Vocational Curricula

Science.gov (United States)

Tutlys, Vidmantas; Spöttl, Georg

2017-01-01

Purpose: This paper aims to explore methodological and institutional challenges on application of the work-process analysis approach in the design and development of competence-based occupational standards for Lithuania. Design/methodology/approach: The theoretical analysis is based on the review of scientific literature and the analysis of…

Web-based turbine cycle performance analysis for nuclear power plants

International Nuclear Information System (INIS)

Heo, Gyun Young; Lee, Sung Jin; Chang, Soon Heung; Choi, Seong Soo

2000-01-01

As an approach to improve the economical efficiency of operating nuclear power plants, a thermal performance analysis tool for steam turbine cycle has been developed. For the validation and the prediction of the signals used in thermal performance analysis, a few statistical signal processing techniques are integrated. The developed tool provides predicted performance calculation capability that is steady-state wet steam turbine cycle simulation, and measurement performance calculation capability which determines component- and cycle-level performance indexes. Web-based interface with all performance analysis is implemented, so even remote users can achieve performance analysis. Comparing to ASME PTC6 (Performance Test Code 6), the focusing point of the developed tool is historical performance analysis rather than single accurate performance test. The proposed signal processing techniques are validated using actual plant signals, and turbine cycle models are tested by benchmarking with a commercial thermal analysis tool

PETRA - an Activity-based Approach to Travel Demand Analysis

DEFF Research Database (Denmark)

Fosgerau, Mogens

2001-01-01

This paper concerns the PETRA model developed by COWI in a project funded by the Danish Ministry of Transport, the Danish Transport Council and the Danish Energy Research Program. The model provides an alternative approach to activity based travel demand analysis that excludes the time dimension...

Voxel-based morphometry and voxel-based diffusion tensor analysis in amyotrophic lateral sclerosis

International Nuclear Information System (INIS)

Chen Zhiye; Ma Lin; Lou Xin; Wang Yan

2010-01-01

Objective: To evaluate gray matter volume, white matter volume and FA value changes in amyatrophic lateral sclerosis (ALS) patients by voxel-based morphometry (VBM) and voxel-based diffusion tensor analysis (VBDTA). Methods: Thirty-nine definite or probable ALS patients diagnosed by El Escorial standard and 39 healthy controls were recruited and underwent conventional MR scans and the neuropsychological evaluation. The 3D FSPGR T 1 WI and DTI data were collected on GE Medical 3.0 T MRI system. The 3DT 1 structural images were normalized, segmented and smoothed, and then VBM analysis was performed. DTI data were acquired from 76 healthy controls, and FA map template was made. FA maps generated from the DTI data of ALS patients and healthy controls were normalized to the FA map template for voxel-based analysis. ANCOVA was applied, controlling with age and total intracranial volume for VBM and age for VBDDTA. A statistical threshold of P<0.01 (uncorrected) and cluster level of more than continuous 20 voxels determined significance. Results: Statistical results showed no significant difference in the global volumes of gray matter and white matter, total intracranial volumes and gray matter fraction between ALS patients and healthy controls, but the white matter fraction of ALS patients (0.29 ± 0.02) was significantly less than that of healthy controls (0.30 ± 0.02) statistically (P=0.003). There was significant reduction of gray matter volumes in bilateral superior frontal gyri and precentral gyri, right middle frontal gyrus, right middle and inferior temporal gyrus, left superior occipital gyrus and cuneus and left insula in ALS patients when compared with healthy controls; and the regional reduction of white matter volumes in ALS patients mainly located in genu of corpus callosum, bilateral medial frontal gyri, paracentral lobule and insula, right superior and middle frontal gyrus and left postcentral gyrus. VBDTA showed decrease in FA values in bilateral

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)