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Sample records for proteomics current state

  1. Proteomics of Staphylococcus aureus--current state and future challenges.

    PubMed

    Hecker, Michael; Engelmann, Susanne; Cordwell, Stuart J

    2003-04-01

    This paper presents a short review of the proteome of Staphylococcus aureus, a gram-positive human pathogen of increasing importance for human health as a result of the increasing antibiotic resistance. A proteome reference map is shown which can be used for future studies and is followed by a demonstration of how proteomics could be applied to obtain new information on S. aureus physiology. The proteomic approach can provide new data on the regulation of metabolism as well as of the stress or starvation responses. Proteomic signatures encompassing specific stress or starvation proteins are excellent tools to predict the physiological state of a cell population. Furthermore proteomics is very useful for analysing the size and function of known and unknown regulons and will open a new dimension in the comprehensive understanding of regulatory networks in pathogenicity. Finally, some fields of application of S. aureus proteomics are discussed, including proteomics and strain evaluation, the role of proteomics for analysis of antibiotic resistance or for discovering new targets and diagnostics tools. The review also shows that the post-genome era of S. aureus which began in 2001 with the publication of the genome sequence is still in a preliminary stage, however, the consequent application of proteomics in combination with DNA array techniques and supported by bioinformatics will provide a comprehensive picture on cell physiology and pathogenicity in the near future. PMID:12659740

  2. The Human Proteome Project: Current State and Future Direction

    PubMed Central

    Legrain, Pierre; Aebersold, Ruedi; Archakov, Alexander; Bairoch, Amos; Bala, Kumar; Beretta, Laura; Bergeron, John; Borchers, Christoph H.; Corthals, Garry L.; Costello, Catherine E.; Deutsch, Eric W.; Domon, Bruno; Hancock, William; He, Fuchu; Hochstrasser, Denis; Marko-Varga, György; Salekdeh, Ghasem Hosseini; Sechi, Salvatore; Snyder, Michael; Srivastava, Sudhir; Uhlén, Mathias; Wu, Cathy H.; Yamamoto, Tadashi; Paik, Young-Ki; Omenn, Gilbert S.

    2011-01-01

    After the successful completion of the Human Genome Project, the Human Proteome Organization has recently officially launched a global Human Proteome Project (HPP), which is designed to map the entire human protein set. Given the lack of protein-level evidence for about 30% of the estimated 20,300 protein-coding genes, a systematic global effort will be necessary to achieve this goal with respect to protein abundance, distribution, subcellular localization, interaction with other biomolecules, and functions at specific time points. As a general experimental strategy, HPP research groups will use the three working pillars for HPP: mass spectrometry, antibody capture, and bioinformatics tools and knowledge bases. The HPP participants will take advantage of the output and cross-analyses from the ongoing Human Proteome Organization initiatives and a chromosome-centric protein mapping strategy, termed C-HPP, with which many national teams are currently engaged. In addition, numerous biologically driven and disease-oriented projects will be stimulated and facilitated by the HPP. Timely planning with proper governance of HPP will deliver a protein parts list, reagents, and tools for protein studies and analyses, and a stronger basis for personalized medicine. The Human Proteome Organization urges each national research funding agency and the scientific community at large to identify their preferred pathways to participate in aspects of this highly promising project in a HPP consortium of funders and investigators. PMID:21742803

  3. The human proteome project: current state and future direction.

    PubMed

    Legrain, Pierre; Aebersold, Ruedi; Archakov, Alexander; Bairoch, Amos; Bala, Kumar; Beretta, Laura; Bergeron, John; Borchers, Christoph H; Corthals, Garry L; Costello, Catherine E; Deutsch, Eric W; Domon, Bruno; Hancock, William; He, Fuchu; Hochstrasser, Denis; Marko-Varga, György; Salekdeh, Ghasem Hosseini; Sechi, Salvatore; Snyder, Michael; Srivastava, Sudhir; Uhlén, Mathias; Wu, Cathy H; Yamamoto, Tadashi; Paik, Young-Ki; Omenn, Gilbert S

    2011-07-01

    After the successful completion of the Human Genome Project, the Human Proteome Organization has recently officially launched a global Human Proteome Project (HPP), which is designed to map the entire human protein set. Given the lack of protein-level evidence for about 30% of the estimated 20,300 protein-coding genes, a systematic global effort will be necessary to achieve this goal with respect to protein abundance, distribution, subcellular localization, interaction with other biomolecules, and functions at specific time points. As a general experimental strategy, HPP research groups will use the three working pillars for HPP: mass spectrometry, antibody capture, and bioinformatics tools and knowledge bases. The HPP participants will take advantage of the output and cross-analyses from the ongoing Human Proteome Organization initiatives and a chromosome-centric protein mapping strategy, termed C-HPP, with which many national teams are currently engaged. In addition, numerous biologically driven and disease-oriented projects will be stimulated and facilitated by the HPP. Timely planning with proper governance of HPP will deliver a protein parts list, reagents, and tools for protein studies and analyses, and a stronger basis for personalized medicine. The Human Proteome Organization urges each national research funding agency and the scientific community at large to identify their preferred pathways to participate in aspects of this highly promising project in a HPP consortium of funders and investigators. PMID:21742803

  4. Making proteomics data accessible and reusable: Current state of proteomics databases and repositories

    PubMed Central

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

    2015-01-01

    Compared to other data-intensive disciplines such as genomics, public deposition and storage of MS-based proteomics, data are still less developed due to, among other reasons, the inherent complexity of the data and the variety of data types and experimental workflows. In order to address this need, several public repositories for MS proteomics experiments have been developed, each with different purposes in mind. The most established resources are the Global Proteome Machine Database (GPMDB), PeptideAtlas, and the PRIDE database. Additionally, there are other useful (in many cases recently developed) resources such as ProteomicsDB, Mass Spectrometry Interactive Virtual Environment (MassIVE), Chorus, MaxQB, PeptideAtlas SRM Experiment Library (PASSEL), Model Organism Protein Expression Database (MOPED), and the Human Proteinpedia. In addition, the ProteomeXchange consortium has been recently developed to enable better integration of public repositories and the coordinated sharing of proteomics information, maximizing its benefit to the scientific community. Here, we will review each of the major proteomics resources independently and some tools that enable the integration, mining and reuse of the data. We will also discuss some of the major challenges and current pitfalls in the integration and sharing of the data. PMID:25158685

  5. The human proteome project: Current state and future direction.

    PubMed

    Legrain, Pierre; Aebersold, Ruedi; Archakov, Alexander; Bairoch, Amos; Bala, Kumar; Beretta, Laura; Bergeron, John; Borchers, Christoph; Corthals, Garry L; Costello, Catherine E; Deutsch, Eric W; Domon, Bruno; Hancock, William; He, Fuchu; Hochstrasser, Denis; Marko-Varga, Gyorgy; Salekdeh, Ghasem Hosseini; Sechi, Salvatore; Snyder, Michael; Srivastava, Sudhir; Uhlen, Mathias; Hu, Cathy H; Yamamoto, Tadashi; Paik, Young-Ki; Omenn, Gilbert S

    2011-04-29

    After successful completion of the Human Genome Project (HGP), HUPO has recently officially launched a global Human Proteome Project (HPP) which is designed to map the entire human protein set. Given the presence of about 30% undisclosed proteins out of 20,300 protein gene products, a systematic global effort is necessary to achieve this goal with respect to protein abundance, distribution, subcellular localization, interaction with other biomolecules, and functions at specific time points. As a general experimental strategy, HPP groups employ the three working pillars for HPP: mass spectrometry, antibody capture, and bioinformatics tools and knowledge base. The HPP participants will take advantage of the output and cross-analyses from the ongoing HUPO initiatives and a chromosome-based protein mapping strategy, termed C-HPP with many national teams currently engaged. In addition, numerous biologically-driven projects will be stimulated and facilitated by the HPP. Timely planning with proper governance of HPP will deliver a protein parts list, reagents and tools for protein studies and analyses, and a stronger basis for personalized medicine. HUPO urges each national research funding agency and the scientific community at large to identify their preferred pathways to participate in aspects of this highly promising project in a HPP consortium of funders and investigators. PMID:21531903

  6. Current application of proteomics in biomarker discovery for inflammatory bowel disease

    PubMed Central

    Chan, Patrick PY; Wasinger, Valerie C; Leong, Rupert W

    2016-01-01

    Recently, the field of proteomics has rapidly expanded in its application towards clinical research with objectives ranging from elucidating disease pathogenesis to discovering clinical biomarkers. As proteins govern and/or reflect underlying cellular processes, the study of proteomics provides an attractive avenue for research as it allows for the rapid identification of protein profiles in a biological sample. Inflammatory bowel disease (IBD) encompasses several heterogeneous and chronic conditions of the gastrointestinal tract. Proteomic technology provides a powerful means of addressing major challenges in IBD today, especially for identifying biomarkers to improve its diagnosis and management. This review will examine the current state of IBD proteomics research and its use in biomarker research. Furthermore, we also discuss the challenges of translating proteomic research into clinically relevant tools. The potential application of this growing field is enormous and is likely to provide significant insights towards improving our future understanding and management of IBD. PMID:26909226

  7. Current application of proteomics in biomarker discovery for inflammatory bowel disease.

    PubMed

    Chan, Patrick Py; Wasinger, Valerie C; Leong, Rupert W

    2016-02-15

    Recently, the field of proteomics has rapidly expanded in its application towards clinical research with objectives ranging from elucidating disease pathogenesis to discovering clinical biomarkers. As proteins govern and/or reflect underlying cellular processes, the study of proteomics provides an attractive avenue for research as it allows for the rapid identification of protein profiles in a biological sample. Inflammatory bowel disease (IBD) encompasses several heterogeneous and chronic conditions of the gastrointestinal tract. Proteomic technology provides a powerful means of addressing major challenges in IBD today, especially for identifying biomarkers to improve its diagnosis and management. This review will examine the current state of IBD proteomics research and its use in biomarker research. Furthermore, we also discuss the challenges of translating proteomic research into clinically relevant tools. The potential application of this growing field is enormous and is likely to provide significant insights towards improving our future understanding and management of IBD. PMID:26909226

  8. Saliva proteome research: current status and future outlook.

    PubMed

    Schulz, Benjamin L; Cooper-White, Justin; Punyadeera, Chamindie K

    2013-09-01

    Human saliva harbours proteins of clinical relevance and about 30% of blood proteins are also present in saliva. This highlights that saliva can be used for clinical applications just as urine or blood. However, the translation of salivary biomarker discoveries into clinical settings is hampered by the dynamics and complexity of the salivary proteome. This review focuses on the current status of technological developments and achievements relating to approaches for unravelling the human salivary proteome. We discuss the dynamics of the salivary proteome, as well as the importance of sample preparation and processing techniques and their influence on downstream protein applications; post-translational modifications of salivary proteome and protein: protein interactions. In addition, we describe possible enrichment strategies for discerning post-translational modifications of salivary proteins, the potential utility of selected-reaction-monitoring techniques for biomarker discovery and validation, limitations to proteomics and the biomarker challenge and future perspectives. In summary, we provide recommendations for practical saliva sampling, processing and storage conditions to increase the quality of future studies in an emerging field of saliva clinical proteomics. We propose that the advent of technologies allowing sensitive and high throughput proteome-wide analyses, coupled to well-controlled study design, will allow saliva to enter clinical practice as an alternative to blood-based methods due to its simplistic nature of sampling, non-invasiveness, easy of collection and multiple collections by untrained professionals and cost-effective advantages. PMID:22612344

  9. Proteomic and other mass spectrometry based "omics" biomarker discovery and validation in pediatric venous thromboembolism and arterial ischemic stroke: current state, unmet needs, and future directions.

    PubMed

    Goldenberg, Neil A; Everett, Allen D; Graham, David; Bernard, Timothy J; Nowak-Göttl, Ulrike

    2014-12-01

    Venous thromboembolism (VTE) and arterial ischemic stroke (AIS) are increasingly-recognized health conditions in children, with both acute and chronic sequelae. Risk factors for, and pathogenesis of, VTE are readily related to three principal factors, consisting of venous stasis, endothelial damage, and the hypercoagulable state (i.e. thrombophilia), termed the triad of Virchow. In children, greater than 90% of VTE are provoked by an overt clinical risk factor, the most common of which is a central venous catheter. Risk factors for childhood-onset (beyond the neonatal period) AIS include sickle cell disease, infection, cerebral arteriopathy, and congenital cardiac disease. In perinatal AIS, risk factors are less well-defined, and have been hypothesized to include maternal-fetal conditions. While some acquired and inherited thrombophilias have been associated with increased risk of incident and/or recurrent VTE and AIS, knowledge of other diagnostic and prognostic biomarkers of VTE/AIS in children remains quite limited. To date, very few published studies have employed plasma mass spectrometry-based "omics" approaches (proteomics, lipidomics or metabolomics). Ongoing and future research efforts involving multicenter prospective study-derived plasma biobanks in pediatric VTE (such as the Kids-DOTT trial) and AIS (including VIPS) along with new multi-omics-compatible sample processing methods offer fertile opportunities for discovery and validation of both novel risk factors and prognostic markers, with great potential to achieve improved prognostic stratification in these diseases. PMID:25379629

  10. Current perspectives in proteomic analysis of abiotic stress in Grapevines

    PubMed Central

    George, Iniga S.; Haynes, Paul A.

    2014-01-01

    Grapes are an important crop plant which forms the basis of a globally important industry. Grape and wine production is particularly vulnerable to environmental and climatic fluctuations, which makes it essential for us to develop a greater understanding of the molecular level responses of grape plants to various abiotic stresses. The completion of the initial grape genome sequence in 2007 has led to a significant increase in research on grapes using proteomics approaches. In this article, we discuss some of the current research on abiotic stress in grapevines, in the context of abiotic stress research in other plant species. We also highlight some of the current limitations in grapevine proteomics and identify areas with promising scope for potential future research. PMID:25538720

  11. Proteome Analysis of Ground State Pluripotency

    PubMed Central

    Taleahmad, Sara; Mirzaei, Mehdi; Parker, Lindsay M.; Hassani, Seyedeh-Nafiseh; Mollamohammadi, Sepideh; Sharifi-Zarchi, Ali; Haynes, Paul A.; Baharvand, Hossein; Salekdeh, Ghasem Hosseini

    2015-01-01

    The differentiation potential of pluripotent embryonic stem cells (ESCs) can be manipulated via serum and medium conditions for direct cellular development or to maintain a naïve ground state. The self-renewal state of ESCs can thus be induced by adding inhibitors of mitogen activated protein kinase (MAPK) and glycogen synthase kinase-3 (Gsk3), known as 2 inhibitors (2i) treatment. We have used a shotgun proteomics approach to investigate differences in protein expressions between 2i- and serum-grown mESCs. The results indicated that 164 proteins were significantly upregulated and 107 proteins downregulated in 2i-grown cells compared to serum. Protein pathways in 2i-grown cells with the highest enrichment were associated with glycolysis and gluconeogenesis. Protein pathways related to organ development were downregulated in 2i-grown cells. In serum-grown ESCs, protein pathways involved in integrin and focal adhesion, and signaling proteins involved in the actin cytoskeleton regulation were enriched. We observed a number of nuclear proteins which were mostly involved in self-renewal maintenance and were expressed at higher levels in 2i compared to serum - Dnmt1, Map2k1, Parp1, Xpo4, Eif3g, Smarca4/Brg1 and Smarcc1/Baf155. Collectively, the results provided an insight into the key protein pathways used by ESCs in the ground state or metastable conditions through 2i or serum culture medium, respectively. PMID:26671762

  12. Asthma and COPD proteomics: current approaches and future directions.

    PubMed

    Terracciano, Rosa; Pelaia, Girolamo; Preianò, Mariaimmacolata; Savino, Rocco

    2015-02-01

    Although asthma and chronic obstructive pulmonary disease COPD represent the two most common chronic respiratory diseases worldwide, the mechanisms underlying their pathobiology need to be further elucidated. Presently, differentiation of asthma and COPD are largely based on clinical and lung function parameters. However, the complexity of these multifactorial diseases may lead to misclassification and to inappropriate management strategies. Recently, tremendous progress in MS has extended the sensitivity, accuracy, and speed of analysis, enabling the identification of thousands of proteins per experiment. Beyond identification, MS has also greatly implemented quantitation issues allowing to assess qualitative-quantitative differences in protein profiles of different samples, in particular diseased versus normal. Herein, we provide a summary of recent proteomics-based investigations in the field of asthma/COPD, highlighting major issues related to sampling and processing procedures for proteomic analyses of specific airway and parenchymal specimens (induced sputum, exhaled breath condensate, epithelial lining fluid, bronchoalveolar and nasal lavage fluid), as well as blood-derived specimen (plasma and serum). Within such a context, together with current difficulties and limitations mainly due to lack of general standardization in preanalytical sampling procedure, our discussion will focus on the challenges and possible benefits of proteomic studies in phenotypic stratification of asthma and COPD. PMID:25504544

  13. Proteomics, biomarkers, and HIV‐1: A current perspective

    PubMed Central

    Donnelly, Maire Rose

    2015-01-01

    Despite more than three decades of extensive research, HIV‐1 infection although well controlled with cART, remains incurable. Multifactorial complexity of the viral life‐cycle poses great challenges in understanding molecular mechanisms underlying this infection and the development of biomarkers, which we hope will lead us to its eradication. For a more in‐depth understanding of how the virus interacts with host target cells, T cells and macrophages, proteomic profiling techniques that offer strategies to investigate the proteome in its entirety were employed. Here, we review proteomic studies related to HIV‐1 infection and discuss perspectives and limitations of proteomic and systems biology approaches in future studies. PMID:26033875

  14. Proteomics and the Analysis of Proteomic Data: 2013 Overview of Current Protein-Profiling Technologies

    PubMed Central

    Bruce, Can; Stone, Kathryn; Gulcicek, Erol; Williams, Kenneth

    2013-01-01

    Mass spectrometry has become a major tool in the study of proteomes. The analysis of proteolytic peptides and their fragment ions by this technique enables the identification and quantitation of the precursor proteins in a mixture. However, deducing chemical structures and then protein sequences from mass-to-charge ratios is a challenging computational task. Software tools incorporating powerful algorithms and statistical methods improved our ability to process the large quantities of proteomics data. Repositories of spectral data make both data analysis and experimental design more efficient. New approaches in quantitative and statistical proteomics make possible a greater coverage of the proteome, the identification of more post-translational modifications and a greater sensitivity in the quantitation of targeted proteins. PMID:23504934

  15. Current strategies and findings in clinically relevant post-translational modification-specific proteomics

    PubMed Central

    Pagel, Oliver; Loroch, Stefan; Sickmann, Albert; Zahedi, René P

    2015-01-01

    Mass spectrometry-based proteomics has considerably extended our knowledge about the occurrence and dynamics of protein post-translational modifications (PTMs). So far, quantitative proteomics has been mainly used to study PTM regulation in cell culture models, providing new insights into the role of aberrant PTM patterns in human disease. However, continuous technological and methodical developments have paved the way for an increasing number of PTM-specific proteomic studies using clinical samples, often limited in sample amount. Thus, quantitative proteomics holds a great potential to discover, validate and accurately quantify biomarkers in body fluids and primary tissues. A major effort will be to improve the complete integration of robust but sensitive proteomics technology to clinical environments. Here, we discuss PTMs that are relevant for clinical research, with a focus on phosphorylation, glycosylation and proteolytic cleavage; furthermore, we give an overview on the current developments and novel findings in mass spectrometry-based PTM research. PMID:25955281

  16. Plant proteomics in India and Nepal: current status and challenges ahead.

    PubMed

    Deswal, Renu; Gupta, Ravi; Dogra, Vivek; Singh, Raksha; Abat, Jasmeet Kaur; Sarkar, Abhijit; Mishra, Yogesh; Rai, Vandana; Sreenivasulu, Yelam; Amalraj, Ramesh Sundar; Raorane, Manish; Chaudhary, Ram Prasad; Kohli, Ajay; Giri, Ashok Prabhakar; Chakraborty, Niranjan; Zargar, Sajad Majeed; Agrawal, Vishwanath Prasad; Agrawal, Ganesh Kumar; Job, Dominique; Renaut, Jenny; Rakwal, Randeep

    2013-10-01

    Plant proteomics has made tremendous contributions in understanding the complex processes of plant biology. Here, its current status in India and Nepal is discussed. Gel-based proteomics is predominantly utilized on crops and non-crops to analyze majorly abiotic (49 %) and biotic (18 %) stress, development (11 %) and post-translational modifications (7 %). Rice is the most explored system (36 %) with major focus on abiotic mainly dehydration (36 %) stress. In spite of expensive proteomics setup and scarcity of trained workforce, output in form of publications is encouraging. To boost plant proteomics in India and Nepal, researchers have discussed ground level issues among themselves and with the International Plant Proteomics Organization (INPPO) to act in priority on concerns like food security. Active collaboration may help in translating this knowledge to fruitful applications. PMID:24431515

  17. Current Status of Proteomic Studies on Defense Responses in Rice.

    PubMed

    Chen, Xifeng; Bhadauria, Vijai; Ma, Bojun

    2016-01-01

    Biotic stresses are constraints to plant growth and development negatively impacting crop production. To counter such stresses, plants have developed stress-specific adaptations as well as simultaneous responses. The efficacy and magnitude of inducible adaptive responses are dependent on activation of signaling pathways and intracellular networks by modulating expression, or abundance, and/or post-translational modification of proteins associated with defense mechanisms. Proteomics plays an important role in elucidating plant defense mechanisms by mining the differential regulation of proteins to various biotic stresses. Rice, one of the most widely cultivated food crops in world, is constantly challenged by a variety of biotic stresses, and high-throughput proteomics approaches have been employed to unravel the molecular mechanism of the biotic stresses-response in rice. In this review, we summarize the latest advances of proteomic studies on defense responses and discuss the potential relevance of the proteins identified by proteomic means in rice defense mechanism. Furthermore, we provide perspective for proteomics in unraveling the molecular mechanism of rice immunity. PMID:26364119

  18. Proteomic evaluation of genetically modified crops: current status and challenges.

    PubMed

    Gong, Chun Yan; Wang, Tai

    2013-01-01

    Hectares of genetically modified (GM) crops have increased exponentially since 1996, when such crops began to be commercialized. GM biotechnology, together with conventional breeding, has become the main approach to improving agronomic traits of crops. However, people are concerned about the safety of GM crops, especially GM-derived food and feed. Many efforts have been made to evaluate the unintended effects caused by the introduction of exogenous genes. "Omics" techniques have advantages over targeted analysis in evaluating such crops because of their use of high-throughput screening. Proteins are key players in gene function and are directly involved in metabolism and cellular development or have roles as toxins, antinutrients, or allergens, which are essential for human health. Thus, proteomics can be expected to become one of the most useful tools in safety assessment. This review assesses the potential of proteomics in evaluating various GM crops. We further describe the challenges in ensuring homogeneity and sensitivity in detection techniques. PMID:23471542

  19. Current Approaches on Viral Infection: Proteomics and Functional Validations

    PubMed Central

    Zheng, Jie; Tan, Boon Huan; Sugrue, Richard; Tang, Kai

    2012-01-01

    Viruses could manipulate cellular machinery to ensure their continuous survival and thus become parasites of living organisms. Delineation of sophisticated host responses upon virus infection is a challenging task. It lies in identifying the repertoire of host factors actively involved in the viral infectious cycle and characterizing host responses qualitatively and quantitatively during viral pathogenesis. Mass spectrometry based proteomics could be used to efficiently study pathogen-host interactions and virus-hijacked cellular signaling pathways. Moreover, direct host and viral responses upon infection could be further investigated by activity-based functional validation studies. These approaches involve drug inhibition of secretory pathway, immunofluorescence staining, dominant negative mutant of protein target, real-time PCR, small interfering siRNA-mediated knockdown, and molecular cloning studies. In this way, functional validation could gain novel insights into the high-content proteomic dataset in an unbiased and comprehensive way. PMID:23162545

  20. Proteomic indicators of oxidation and hydration state in colorectal cancer

    PubMed Central

    2016-01-01

    New integrative approaches are needed to harness the potential of rapidly growing datasets of protein expression and microbial community composition in colorectal cancer. Chemical and thermodynamic models offer theoretical tools to describe populations of biomacromolecules and their relative potential for formation in different microenvironmental conditions. The average oxidation state of carbon (ZC) can be calculated as an elemental ratio from the chemical formulas of proteins, and water demand per residue (\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{upgreek} \\usepackage{mathrsfs} \\setlength{\\oddsidemargin}{-69pt} \\begin{document} }{}${\\overline{n}}_{{\\mathrm{H}}_{2}\\mathrm{O}}$\\end{document}n¯H2O) is computed by writing the overall formation reactions of proteins from basis species. Using results reported in proteomic studies of clinical samples, many datasets exhibit higher mean ZC or \\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{upgreek} \\usepackage{mathrsfs} \\setlength{\\oddsidemargin}{-69pt} \\begin{document} }{}${\\overline{n}}_{{\\mathrm{H}}_{2}\\mathrm{O}}$\\end{document}n¯H2O of proteins in carcinoma or adenoma compared to normal tissue. In contrast, average protein compositions in bacterial genomes often have lower ZC for bacteria enriched in fecal samples from cancer patients compared to healthy donors. In thermodynamic calculations, the potential for formation of the cancer-related proteins is energetically favored by changes in the chemical activity of H2O and fugacity of O2 that reflect the compositional differences. The compositional analysis suggests that a systematic change in chemical composition is an essential feature of cancer proteomes, and the thermodynamic descriptions show that the observed proteomic

  1. Proteomic evaluation of genetically modified crops: current status and challenges

    PubMed Central

    Gong, Chun Yan; Wang, Tai

    2013-01-01

    Hectares of genetically modified (GM) crops have increased exponentially since 1996, when such crops began to be commercialized. GM biotechnology, together with conventional breeding, has become the main approach to improving agronomic traits of crops. However, people are concerned about the safety of GM crops, especially GM-derived food and feed. Many efforts have been made to evaluate the unintended effects caused by the introduction of exogenous genes. “Omics” techniques have advantages over targeted analysis in evaluating such crops because of their use of high-throughput screening. Proteins are key players in gene function and are directly involved in metabolism and cellular development or have roles as toxins, antinutrients, or allergens, which are essential for human health. Thus, proteomics can be expected to become one of the most useful tools in safety assessment. This review assesses the potential of proteomics in evaluating various GM crops. We further describe the challenges in ensuring homogeneity and sensitivity in detection techniques. PMID:23471542

  2. Challenges, current status and future perspectives of proteomics in improving understanding, diagnosis and treatment of vascular disease

    PubMed Central

    Moxon, Joseph V.; Padula, Matthew P.; Herbert, Ben R.; Golledge, Jonathan

    2009-01-01

    Technical advances have seen the rapid adoption of genomics and multiplex genetic polymorphism identification to research on vascular diseases. The utilization of proteomics for the study of vascular diseases has been limited by comparison. In this review we outline currently available proteomics techniques, the challenges to using these approaches and modifications which may improve the utilization of proteomics in the study of vascular diseases. PMID:19541510

  3. Multiplexed immunofluorescence delineates proteomic cancer cell states associated with metabolism

    PubMed Central

    Sood, Anup; Miller, Alexandra M.; Brogi, Edi; Sui, Yunxia; Armenia, Joshua; McDonough, Elizabeth; Santamaria-Pang, Alberto; Carlin, Sean; Stamper, Aleksandra; Campos, Carl; Pang, Zhengyu; Li, Qing; Port, Elisa; Graeber, Thomas G.; Schultz, Nikolaus; Ginty, Fiona; Larson, Steven M.; Mellinghoff, Ingo K.

    2016-01-01

    The phenotypic diversity of cancer results from genetic and nongenetic factors. Most studies of cancer heterogeneity have focused on DNA alterations, as technologies for proteomic measurements in clinical specimen are currently less advanced. Here, we used a multiplexed immunofluorescence staining platform to measure the expression of 27 proteins at the single-cell level in formalin-fixed and paraffin-embedded samples from treatment-naive stage II/III human breast cancer. Unsupervised clustering of protein expression data from 638,577 tumor cells in 26 breast cancers identified 8 clusters of protein coexpression. In about one-third of breast cancers, over 95% of all neoplastic cells expressed a single protein coexpression cluster. The remaining tumors harbored tumor cells representing multiple protein coexpression clusters, either in a regional distribution or intermingled throughout the tumor. Tumor uptake of the radiotracer 18F-fluorodeoxyglucose was associated with protein expression clusters characterized by hormone receptor loss, PTEN alteration, and HER2 gene amplification. Our study demonstrates an approach to generate cellular heterogeneity metrics in routinely collected solid tumor specimens and integrate them with in vivo cancer phenotypes. PMID:27182557

  4. Designing biomedical proteomics experiments: state-of-the-art and future perspectives.

    PubMed

    Maes, Evelyne; Kelchtermans, Pieter; Bittremieux, Wout; De Grave, Kurt; Degroeve, Sven; Hooyberghs, Jef; Mertens, Inge; Baggerman, Geert; Ramon, Jan; Laukens, Kris; Martens, Lennart; Valkenborg, Dirk

    2016-05-01

    With the current expanded technical capabilities to perform mass spectrometry-based biomedical proteomics experiments, an improved focus on the design of experiments is crucial. As it is clear that ignoring the importance of a good design leads to an unprecedented rate of false discoveries which would poison our results, more and more tools are developed to help researchers designing proteomic experiments. In this review, we apply statistical thinking to go through the entire proteomics workflow for biomarker discovery and validation and relate the considerations that should be made at the level of hypothesis building, technology selection, experimental design and the optimization of the experimental parameters. PMID:27031651

  5. Proteomics of boar seminal plasma - current studies and possibility of their application in biotechnology of animal reproduction.

    PubMed

    Strzeżek, Jerzy; Wysocki, Paweł; Kordan, Władysław; Kuklińska, Magdalena; Mogielnicka, Marzena; Soliwoda, Daniel; Fraser, Leyland

    2005-11-01

    Proteomics is critical to identify the properties and functions of proteins involved in the mechanism regulating the male reproductive tract function. This approach is important in male fertility assessment and clinical diagnosis of the physiological state of individual reproductive organs. Proteomics also provides a tool to understand the interactions of seminal plasma proteins with spermatozoa, which could provide a useful model for studying ligand-cell interaction occurring at the sperm cell surface. This review covers a selection of advances in the realm of functional proteomics of boar seminal plasma proteins and is focused on some fundamental proteomic technologies. Also, this review explores key themes in proteomics and their application in animal reproductive techniques. PMID:16372045

  6. Covering complete proteomes with X-ray structures: a current snapshot

    SciTech Connect

    Mizianty, Marcin J.; Fan, Xiao; Yan, Jing; Chalmers, Eric; Woloschuk, Christopher; Joachimiak, Andrzej; Kurgan, Lukasz

    2014-11-01

    The current and the attainable coverage by X-ray structures of proteins and their functions on the scale of the ‘protein universe’ are estimated. A detailed analysis of the coverage across nearly 2000 proteomes from all superkingdoms of life and functional annotations is performed, with particular focus on the human proteome and the family of GPCR proteins. Structural genomics programs have developed and applied structure-determination pipelines to a wide range of protein targets, facilitating the visualization of macromolecular interactions and the understanding of their molecular and biochemical functions. The fundamental question of whether three-dimensional structures of all proteins and all functional annotations can be determined using X-ray crystallography is investigated. A first-of-its-kind large-scale analysis of crystallization propensity for all proteins encoded in 1953 fully sequenced genomes was performed. It is shown that current X-ray crystallographic knowhow combined with homology modeling can provide structures for 25% of modeling families (protein clusters for which structural models can be obtained through homology modeling), with at least one structural model produced for each Gene Ontology functional annotation. The coverage varies between superkingdoms, with 19% for eukaryotes, 35% for bacteria and 49% for archaea, and with those of viruses following the coverage values of their hosts. It is shown that the crystallization propensities of proteomes from the taxonomic superkingdoms are distinct. The use of knowledge-based target selection is shown to substantially increase the ability to produce X-ray structures. It is demonstrated that the human proteome has one of the highest attainable coverage values among eukaryotes, and GPCR membrane proteins suitable for X-ray structure determination were determined.

  7. Cerebrospinal fluid proteomics and protein biomarkers in frontotemporal lobar degeneration: Current status and future perspectives.

    PubMed

    Oeckl, Patrick; Steinacker, Petra; Feneberg, Emily; Otto, Markus

    2015-07-01

    Frontotemporal lobar degeneration (FTLD) comprises a spectrum of rare neurodegenerative diseases with an estimated prevalence of 15-22 cases per 100,000 persons including the behavioral variant of frontotemporal dementia (bvFTD), progressive non-fluent aphasia (PNFA), semantic dementia (SD), FTD with motor neuron disease (FTD-MND), progressive supranuclear palsy (PSP) and corticobasal syndrome (CBS). The pathogenesis of the diseases is still unclear and clinical diagnosis of FTLD is hampered by overlapping symptoms within the FTLD subtypes and with other neurodegenerative diseases such as Alzheimer's disease (AD) and Parkinson's disease (PD). Intracellular protein aggregates in the brain are a major hallmark of FTLD and implicate alterations in protein metabolism or function in the disease's pathogenesis. Cerebrospinal fluid (CSF) which surrounds the brain can be used to study changes in neurodegenerative diseases and to identify disease-related mechanisms or neurochemical biomarkers for diagnosis. In the present review, we will give an overview of the current literature on proteomic studies in CSF of FTLD patients. Reports of targeted and unbiased proteomic approaches are included and the results are discussed in regard of their informative value about disease pathology and the suitability to be used as diagnostic biomarkers. Finally, we will give some future perspectives on CSF proteomics and a list of candidate biomarkers which might be interesting for validation in further studies. This article is part of a Special Issue entitled: Neuroproteomics: Applications in neuroscience and neurology. PMID:25526887

  8. Covering complete proteomes with X-ray structures: A current snapshot

    SciTech Connect

    Mizianty, Marcin J.; Fan, Xiao; Yan, Jing; Chalmers, Eric; Woloschuk, Christopher; Joachimiak, Andrzej; Kurgan, Lukasz

    2014-10-23

    Structural genomics programs have developed and applied structure-determination pipelines to a wide range of protein targets, facilitating the visualization of macromolecular interactions and the understanding of their molecular and biochemical functions. The fundamental question of whether three-dimensional structures of all proteins and all functional annotations can be determined using X-ray crystallography is investigated. A first-of-its-kind large-scale analysis of crystallization propensity for all proteins encoded in 1953 fully sequenced genomes was performed. It is shown that current X-ray crystallographic knowhow combined with homology modeling can provide structures for 25% of modeling families (protein clusters for which structural models can be obtained through homology modeling), with at least one structural model produced for each Gene Ontology functional annotation. The coverage varies between superkingdoms, with 19% for eukaryotes, 35% for bacteria and 49% for archaea, and with those of viruses following the coverage values of their hosts. It is shown that the crystallization propensities of proteomes from the taxonomic superkingdoms are distinct. The use of knowledge-based target selection is shown to substantially increase the ability to produce X-ray structures. It is demonstrated that the human proteome has one of the highest attainable coverage values among eukaryotes, and GPCR membrane proteins suitable for X-ray structure determination were determined.

  9. Covering complete proteomes with X-ray structures: A current snapshot

    DOE PAGESBeta

    Mizianty, Marcin J.; Fan, Xiao; Yan, Jing; Chalmers, Eric; Woloschuk, Christopher; Joachimiak, Andrzej; Kurgan, Lukasz

    2014-10-23

    Structural genomics programs have developed and applied structure-determination pipelines to a wide range of protein targets, facilitating the visualization of macromolecular interactions and the understanding of their molecular and biochemical functions. The fundamental question of whether three-dimensional structures of all proteins and all functional annotations can be determined using X-ray crystallography is investigated. A first-of-its-kind large-scale analysis of crystallization propensity for all proteins encoded in 1953 fully sequenced genomes was performed. It is shown that current X-ray crystallographic knowhow combined with homology modeling can provide structures for 25% of modeling families (protein clusters for which structural models can be obtainedmore » through homology modeling), with at least one structural model produced for each Gene Ontology functional annotation. The coverage varies between superkingdoms, with 19% for eukaryotes, 35% for bacteria and 49% for archaea, and with those of viruses following the coverage values of their hosts. It is shown that the crystallization propensities of proteomes from the taxonomic superkingdoms are distinct. The use of knowledge-based target selection is shown to substantially increase the ability to produce X-ray structures. It is demonstrated that the human proteome has one of the highest attainable coverage values among eukaryotes, and GPCR membrane proteins suitable for X-ray structure determination were determined.« less

  10. Steady State Tokamak Equilibria without Current Drive

    SciTech Connect

    Shaing, K.C.; Aydemir, A.Y.; Lin-Liu, Y.R.; Miller, R.L.

    1997-11-01

    Steady state tokamak equilibria without current drive are found. This is made possible by including the potato bootstrap current close to the magnetic axis. Tokamaks with this class of equilibria do not need seed current or current drive, and are intrinsically steady state. {copyright} {ital 1997} {ital The American Physical Society}

  11. GENOMIC AND PROTEOMIC ANALYSIS OF SURROGATE TISSUES FOR ASSESSING TOXIC EXPOSURES AND DISEASE STATES

    EPA Science Inventory

    Genomic and Proteomic Analysis of Surrogate Tissues for Assessing Toxic Exposures and Disease States
    David J. Dix and John C. Rockett
    Reproductive Toxicology Division, National Health and Environmental Effects Research Laboratory, Office of Research and Development, USEPA, ...

  12. Solid-state current transformer

    NASA Technical Reports Server (NTRS)

    Farnsworth, D. L. (Inventor)

    1976-01-01

    A signal transformation network which is uniquely characterized to exhibit a very low input impedance while maintaining a linear transfer characteristic when driven from a voltage source and when quiescently biased in the low microampere current range is described. In its simplest form, it consists of a tightly coupled two transistor network in which a common emitter input stage is interconnected directly with an emitter follower stage to provide virtually 100 percent negative feedback to the base input of the common emitter stage. Bias to the network is supplied via the common tie point of the common emitter stage collector terminal and the emitter follower base stage terminal by a regulated constant current source, and the output of the circuit is taken from the collector of the emitter follower stage.

  13. Solid state electrochemical current source

    DOEpatents

    Potanin, Alexander Arkadyevich; Vedeneev, Nikolai Ivanovich

    2002-04-30

    A cathode and a solid state electrochemical cell comprising said cathode, a solid anode and solid fluoride ion conducting electrolyte. The cathode comprises a metal oxide and a compound fluoride containing at least two metals with different valences. Representative compound fluorides include solid solutions of bismuth fluoride and potassium fluoride; and lead fluoride and potassium fluoride. Representative metal oxides include copper oxide, lead oxide, manganese oxide, vanadium oxide and silver oxide.

  14. Rosacea: current state of epidemiology.

    PubMed

    Tan, Jerry; Berg, Mats

    2013-12-01

    Case definitions are critical in epidemiologic research. However, modern disease indicators must now consider complex data from gene-based research along with traditional clinical parameters. Rosacea is a skin disorder with multiple signs and symptoms. In individuals, these features may be multiple or one may predominate. While studies on the epidemiology of rosacea have previously been sparse, there has been a recent increase in research activity. A broader body of epidemiological information that includes a greater variety of countries beyond Northern Europe and general population-based demographics is needed. As there are operational issues in current case definitions of rosacea subtypes--rationalization and standardization--universal consistent applications in future research is also imperative. Further improvement in disease definition combining new research information along with clinical pragmatism should increase the accuracy of rosacea case ascertainment and facilitate further epidemiological research. PMID:24229634

  15. Comparative proteome analysis of Milnesium tardigradum in early embryonic state versus adults in active and anhydrobiotic state.

    PubMed

    Schokraie, Elham; Warnken, Uwe; Hotz-Wagenblatt, Agnes; Grohme, Markus A; Hengherr, Steffen; Förster, Frank; Schill, Ralph O; Frohme, Marcus; Dandekar, Thomas; Schnölzer, Martina

    2012-01-01

    Tardigrades have fascinated researchers for more than 300 years because of their extraordinary capability to undergo cryptobiosis and survive extreme environmental conditions. However, the survival mechanisms of tardigrades are still poorly understood mainly due to the absence of detailed knowledge about the proteome and genome of these organisms. Our study was intended to provide a basis for the functional characterization of expressed proteins in different states of tardigrades. High-throughput, high-accuracy proteomics in combination with a newly developed tardigrade specific protein database resulted in the identification of more than 3000 proteins in three different states: early embryonic state and adult animals in active and anhydrobiotic state. This comprehensive proteome resource includes protein families such as chaperones, antioxidants, ribosomal proteins, cytoskeletal proteins, transporters, protein channels, nutrient reservoirs, and developmental proteins. A comparative analysis of protein families in the different states was performed by calculating the exponentially modified protein abundance index which classifies proteins in major and minor components. This is the first step to analyzing the proteins involved in early embryonic development, and furthermore proteins which might play an important role in the transition into the anhydrobiotic state. PMID:23029181

  16. Comparative proteome analysis of Milnesium tardigradum in early embryonic state versus adults in active and anhydrobiotic state

    PubMed Central

    Schokraie, Elham; Warnken, Uwe; Hotz-Wagenblatt, Agnes; Grohme, Markus A.; Hengherr, Steffen; Förster, Frank; Schill, Ralph O.; Frohme, Marcus; Dandekar, Thomas; Schnölzer, Martina

    2012-01-01

    Tardigrades have fascinated researchers for more than 300 years because of their extraordinary capability to undergo cryptobiosis and survive extreme environmental conditions. However, the survival mechanisms of tardigrades are still poorly understood mainly due to the absence of detailed knowledge about the proteome and genome of these organisms. Our study was intended to provide a basis for the functional characterization of expressed proteins in different states of tardigrades. High-throughput, high-accuracy proteomics in combination with a newly developed tardigrade specific protein database resulted in the identification of more than 3000 proteins in three different states: early embryonic state and adult animals in active and anhydrobiotic state. This comprehensive proteome resource includes protein families such as chaperones, antioxidants, ribosomal proteins, cytoskeletal proteins, transporters, protein channels, nutrient reservoirs, and developmental proteins. A comparative analysis of protein families in the different states was performed by calculating the exponentially modified protein abundance index which classifies proteins in major and minor components. This is the first step to analyzing the proteins involved in early embryonic development, and furthermore proteins which might play an important role in the transition into the anhydrobiotic state. PMID:23029181

  17. Large-Scale, Ion-Current-Based Proteomic Investigation of the Rat Striatal Proteome in a Model of Short- and Long-Term Cocaine Withdrawal.

    PubMed

    Shen, Shichen; Jiang, Xiaosheng; Li, Jun; Straubinger, Robert M; Suarez, Mauricio; Tu, Chengjian; Duan, Xiaotao; Thompson, Alexis C; Qu, Jun

    2016-05-01

    Given the tremendous detriments of cocaine dependence, effective diagnosis and patient stratification are critical for successful intervention yet difficult to achieve due to the largely unknown molecular mechanisms involved. To obtain new insights into cocaine dependence and withdrawal, we employed a reproducible, reliable, and large-scale proteomics approach to investigate the striatal proteomes of rats (n = 40, 10 per group) subjected to chronic cocaine exposure, followed by either short- (WD1) or long- (WD22) term withdrawal. By implementing a surfactant-aided precipitation/on-pellet digestion procedure, a reproducible and sensitive nanoLC-Orbitrap MS analysis, and an optimized ion-current-based MS1 quantification pipeline, >2000 nonredundant proteins were quantified confidently without missing data in any replicate. Although cocaine was cleared from the body, 129/37 altered proteins were observed in WD1/WD22 that are implicated in several biological processes related closely to drug-induced neuroplasticity. Although many of these changes recapitulate the findings from independent studies reported over the last two decades, some novel insights were obtained and further validated by immunoassays. For example, significantly elevated striatal protein kinase C activity persisted over the 22 day cocaine withdrawal. Cofilin-1 activity was up-regulated in WD1 and down-regulated in WD22. These discoveries suggest potentially distinct structural plasticity after short- and long-term cocaine withdrawal. In addition, this study provides compelling evidence that blood vessel narrowing, a long-known effect of cocaine use, occurred after long-term but not short-term withdrawal. In summary, this work developed a well-optimized paradigm for ion-current-based quantitative proteomics in brain tissues and obtained novel insights into molecular alterations in the striatum following cocaine exposure and withdrawal. PMID:27018876

  18. Nanoscaled Proteomic Analysis

    NASA Astrophysics Data System (ADS)

    Xu, Yan; Jia, Lee

    2013-09-01

    Global proteomics research is currently hampered by the extremely complexity of the proteome and the absence of techniques like the polymerase chain reaction in genomics which enables multiplication of a single protein molecule. Since all the existing analytical technologies cannot overcome the detection limit and the dynamic concentration barrier, development of improved analytical technologies at nanoscale, ideally those that could recognize single protein molecule in the presence of high abundant of others, is a high priority for proteomics. In this chapter, we will show the state-of-the-art of nanoproteomics, i.e., the application of nanotechnologies to proteomics. Various nanomaterials including carbon nanomaterials, magnetic nanoparticles, silica nanoparticles, polymer and copolymer nanoparticles, metal and metal oxide nanoparticles have been used to improve sensitivity, specificity, and repeatability of proteomic analysis especially when the multidimensional separation system coupled with MALDI-TOF-MS is used. Among them, gold nanoparticles (GNPs) and carbon nanotubes (CNTs) are the two most important nanomaterials: while GNPs are frequently utilized for enzyme immobilization, high throughput bioassay, selection of target-peptides and target-protein, CNTs including single-walled carbon nanotubes (SWCNTs) and mutiple-walled carbon nanotubes (MWCNTs) have wide applications to electronic sensor, sensitive immunodetection, nanobiocatalysis, affinity probes, MALDI matrices, protein digestion, peptides enrichment and analysis. In perspectives, a deep understanding of the structures and property of nanomaterials and interdisciplinary applications of nanotechnology to proteomics will certainly be revolutionary and intellectually rewarding.

  19. Protein lysine acetylation in bacteria: Current state of the art.

    PubMed

    Ouidir, Tassadit; Kentache, Takfarinas; Hardouin, Julie

    2016-01-01

    Post-translational modifications of proteins are key events in cellular metabolism and physiology regulation. Lysine acetylation is one of the best studied protein modifications in eukaryotes, but, until recently, ignored in bacteria. However, proteomic advances have highlighted the diversity of bacterial lysine-acetylated proteins. The current data support the implication of lysine acetylation in various metabolic pathways, adaptation and virulence. In this review, we present a broad overview of the current knowledge of lysine acetylation in bacteria. We emphasize particularly the significant contribution of proteomics in this field. PMID:26390373

  20. The Discovery of Novel Genomic, Transcriptomic, and Proteomic Biomarkers in Cardiovascular and Peripheral Vascular Disease: The State of the Art

    PubMed Central

    de Franciscis, Stefano; Metzinger, Laurent; Serra, Raffaele

    2016-01-01

    Cardiovascular disease (CD) and peripheral vascular disease (PVD) are leading causes of mortality and morbidity in western countries and also responsible of a huge burden in terms of disability, functional decline, and healthcare costs. Biomarkers are measurable biological elements that reflect particular physiological or pathological states or predisposition towards diseases and they are currently widely studied in medicine and especially in CD. In this context, biomarkers can also be used to assess the severity or the evolution of several diseases, as well as the effectiveness of particular therapies. Genomics, transcriptomics, and proteomics have opened new windows on disease phenomena and may permit in the next future an effective development of novel diagnostic and prognostic medicine in order to better prevent or treat CD. This review will consider the current evidence of novel biomarkers with clear implications in the improvement of risk assessment, prevention strategies, and medical decision making in the field of CD. PMID:27298828

  1. Proteomic and Phospho-Proteomic Profile of Human Platelets in Basal, Resting State: Insights into Integrin Signaling

    PubMed Central

    Maiguel, Dony; Faridi, Mohd Hafeez; Barth, Constantinos J.; Salem, Saeed M.; Singhal, Mudita; Stoub, Darren; Krastins, Bryan; Ogihara, Mitsunori; Zaki, Mohammed J.; Gupta, Vineet

    2009-01-01

    During atherogenesis and vascular inflammation quiescent platelets are activated to increase the surface expression and ligand affinity of the integrin αIIbβ3 via inside-out signaling. Diverse signals such as thrombin, ADP and epinephrine transduce signals through their respective GPCRs to activate protein kinases that ultimately lead to the phosphorylation of the cytoplasmic tail of the integrin αIIbβ3 and augment its function. The signaling pathways that transmit signals from the GPCR to the cytosolic domain of the integrin are not well defined. In an effort to better understand these pathways, we employed a combination of proteomic profiling and computational analyses of isolated human platelets. We analyzed ten independent human samples and identified a total of 1507 unique proteins in platelets. This is the most comprehensive platelet proteome assembled to date and includes 190 membrane-associated and 262 phosphorylated proteins, which were identified via independent proteomic and phospho-proteomic profiling. We used this proteomic dataset to create a platelet protein-protein interaction (PPI) network and applied novel contextual information about the phosphorylation step to introduce limited directionality in the PPI graph. This newly developed contextual PPI network computationally recapitulated an integrin signaling pathway. Most importantly, our approach not only provided insights into the mechanism of integrin αIIbβ3 activation in resting platelets but also provides an improved model for analysis and discovery of PPI dynamics and signaling pathways in the future. PMID:19859549

  2. Solid state recording current meter conversion

    USGS Publications Warehouse

    Cheng, Ralph T.; Wang, Lichen

    1985-01-01

    The authors describe the conversion of an Endeco-174 current meter to a solid-state recording current meter. A removable solid-state module was designed to fit in the space originally occupied by an 8-track tape cartridge. The module contains a CPU and 128 kilobytes of nonvolatile CMOS memory. The solid-state module communicates with any terminal or computer using an RS-232C interface at 4800 baud rate. A primary consideration for conversion was to keep modifications of the current meter to a minimum. The communication protocol was designed to emulate the Endeco tape translation unit, thus the need for a translation unit was eliminated and the original data reduction programs can be used without any modification. After conversion, the data recording section of the current meter contains no moving parts; the storage capacity of the module is equivalent to that of the original tape cartridge.

  3. Current Progress in Tonoplast Proteomics Reveals Insights into the Function of the Large Central Vacuole

    PubMed Central

    Trentmann, Oliver; Haferkamp, Ilka

    2013-01-01

    Vacuoles of plants fulfill various biologically important functions, like turgor generation and maintenance, detoxification, solute sequestration, or protein storage. Different types of plant vacuoles (lytic versus protein storage) are characterized by different functional properties apparently caused by a different composition/abundance and regulation of transport proteins in the surrounding membrane, the tonoplast. Proteome analyses allow the identification of vacuolar proteins and provide an informative basis for assigning observed transport processes to specific carriers or channels. This review summarizes techniques required for vacuolar proteome analyses, like e.g., isolation of the large central vacuole or tonoplast membrane purification. Moreover, an overview about diverse published vacuolar proteome studies is provided. It becomes evident that qualitative proteomes from different plant species represent just the tip of the iceberg. During the past few years, mass spectrometry achieved immense improvement concerning its accuracy, sensitivity, and application. As a consequence, modern tonoplast proteome approaches are suited for detecting alterations in membrane protein abundance in response to changing environmental/physiological conditions and help to clarify the regulation of tonoplast transport processes. PMID:23459586

  4. The audacity of proteomics: a chance to overcome current challenges in schizophrenia research.

    PubMed

    Baloyianni, Nicoletta; Tsangaris, George Th

    2009-12-01

    The evidence on the mechanisms underlying schizophrenia seems to support a series of divergent possibilities that may play a contributory role in the disease pathogenesis. Hypotheses regarding disease mechanisms range from structural and neurodevelopmental abnormalities to neurotransmitter deficits and genetic predisposition. Nevertheless, little progress has been made in the field of schizophrenia with respect to the key pathophysiological processes, and this is a fundamental barrier to identifying or predicting the therapeutic value of novel drug targets. All multi-omics approaches, including proteomics, would be perfectly suited to such a complex disease as a means of tackling the widening chasm between the aforementioned hypotheses. Proteomic studies have been performed in a variety of tissues and biological fluids, from post-mortem CNS tissue to cerebrospinal fluid and blood, and in recently generated mutant animal models with schizophrenia-like phenotypes. In this review, we present an overview of several proteomic studies in the field of schizophrenia research and discuss how proteomics could assist with identifying schizophrenia markers more efficiently, covering both clinical and basic research. PMID:19929611

  5. Deep Imaging: How Much of the Proteome Does Current Top-Down Technology Already Resolve?

    PubMed Central

    Wright, Elise P.; Prasad, Kali A. G.; Padula, Matthew P.; Coorssen, Jens R.

    2014-01-01

    Effective proteome analyses are based on interplay between resolution and detection. It had been claimed that resolution was the main factor limiting the use of two-dimensional gel electrophoresis. Improved protein detection now indicates that this is unlikely to be the case. Using a highly refined protocol, the rat brain proteome was extracted, resolved, and detected. In order to overcome the stain saturation threshold, high abundance protein species were excised from the gel following standard imaging. Gels were then imaged again using longer exposure times, enabling detection of lower abundance, less intensely stained protein species. This resulted in a significant enhancement in the detection of resolved proteins, and a slightly modified digestion protocol enabled effective identification by standard mass spectrometric methods. The data indicate that the resolution required for comprehensive proteome analyses is already available, can assess multiple samples in parallel, and preserve critical information concerning post-translational modifications. Further optimization of staining and detection methods promises additional improvements to this economical, widely accessible and effective top-down approach to proteome analysis. PMID:24489691

  6. Progress in Mining the Human Proteome for Disease Applications

    PubMed Central

    2011-01-01

    Abstract Currently available technologies allow in-depth analysis of multiple facets of the proteome that have clinical relevance and that complement current genomics-based approaches. Although some progress has been made in our knowledge of the human proteome in health and in disease, there is an urgent need to chart a coherent road map with clearly defined milestones to guide proteomics efforts. Areas of emphasis include: (1) building resources, (2) filling gaps in our understanding of biological variation, and (3) systematically characterizing proteome alterations that occur in well-defined disease states, all of which require an organized and collaborative effort. PMID:21375461

  7. Proteome turnover in bacteria: current status for Corynebacterium glutamicum and related bacteria

    PubMed Central

    Trötschel, Christian; Albaum, Stefan P; Poetsch, Ansgar

    2013-01-01

    With the advent of high-resolution mass spectrometry together with sophisticated data analysis and interpretation algorithms, determination of protein synthesis and degradation rates (i.e. protein turnover) on a proteome-wide scale by employing stable isotope-labelled amino acids has become feasible. These dynamic data provide a deeper understanding of protein homeostasis and stress response mechanisms in microorganisms than well-established ‘steady state’ proteomics approaches. In this article, we summarize the technological challenges and solutions both on the biochemistry/mass spectrometry and bioinformatics level for turnover proteomics with a focus on chromatographic techniques. Although the number of available case studies for Corynebacterium glutamicum and related actinobacteria is still very limited, our review illustrates the potential of protein turnover studies for an improved understanding of questions in the area of biotechnology and biomedicine. Here, new insights from investigations of growth phase transition and different stress dynamics including iron, acid and heat stress for pathogenic but also for industrial actinobacteria are presented. Finally, we will comment on the advantages of integrated software solutions for biologists and briefly discuss the remaining technical challenges and upcoming possibilities for protein turnover analysis. PMID:23425033

  8. Colonization State Influences the Hemocyte Proteome in a Beneficial Squid–Vibrio Symbiosis*

    PubMed Central

    Schleicher, Tyler R.; VerBerkmoes, Nathan C.; Shah, Manesh; Nyholm, Spencer V.

    2014-01-01

    The squid Euprymna scolopes and the luminescent bacterium Vibrio fischeri form a highly specific beneficial light organ symbiosis. Not only does the host have to select V. fischeri from the environment, but it must also prevent subsequent colonization by non-symbiotic microorganisms. Host macrophage-like hemocytes are believed to play a role in mediating the symbiosis with V. fischeri. Previous studies have shown that the colonization state of the light organ influences the host's hemocyte response to the symbiont. To further understand the molecular mechanisms behind this process, we used two quantitative mass-spectrometry-based proteomic techniques, isobaric tags for relative and absolute quantification (iTRAQ) and label-free spectral counting, to compare and quantify the adult hemocyte proteomes from colonized (sym) and uncolonized (antibiotic-treated/cured) squid. Overall, iTRAQ allowed for the quantification of 1,024 proteins with two or more peptides. Thirty-seven unique proteins were determined to be significantly different between sym and cured hemocytes (p value < 0.05), with 20 more abundant proteins and 17 less abundant in sym hemocytes. The label-free approach resulted in 1,241 proteins that were identified in all replicates. Of 185 unique proteins present at significantly different amounts in sym hemocytes (as determined by spectral counting), 92 were more abundant and 93 were less abundant. Comparisons between iTRAQ and spectral counting revealed that 30 of the 37 proteins quantified via iTRAQ exhibited trends similar to those identified by the label-free method. Both proteomic techniques mutually identified 16 proteins that were significantly different between the two groups of hemocytes (p value < 0.05). The presence of V. fischeri in the host light organ influenced the abundance of proteins associated with the cytoskeleton, adhesion, lysosomes, proteolysis, and the innate immune response. These data provide evidence that colonization by V. fischeri

  9. Molecular chaperones: guardians of the proteome in normal and disease states

    PubMed Central

    Jeng, Wilson; Lee, Sukyeong; Sung, Nuri; Lee, Jungsoon; Tsai, Francis T.F.

    2015-01-01

    Proteins must adopt a defined three-dimensional structure in order to gain functional activity, or must they? An ever-increasing number of intrinsically disordered proteins and amyloid-forming polypeptides challenge this dogma. While molecular chaperones and proteases are traditionally associated with protein quality control inside the cell, it is now apparent that molecular chaperones not only promote protein folding in the “forward” direction by facilitating folding and preventing misfolding and aggregation, but also facilitate protein unfolding and even disaggregation resulting in the recovery of functional protein from aggregates. Here, we review our current understanding of ATP-dependent molecular chaperones that harness the energy of ATP binding and hydrolysis to fuel their chaperone functions. An emerging theme is that most of these chaperones do not work alone, but instead function together with other chaperone systems to maintain the proteome. Hence, molecular chaperones are the major component of the proteostasis network that guards and protects the proteome from damage. Furthermore, while a decline of this network is detrimental to cell and organismal health, a controlled perturbation of the proteostasis network may offer new therapeutic avenues against human diseases. PMID:26918154

  10. Proteome Analysis of Rat Hippocampus Following Morphine-induced Amnesia and State-dependent Learning

    PubMed Central

    Jafarinejad-Farsangi, Saeideh; Farazmand, Ali; Rezayof, Ameneh; Darbandi, Niloufar

    2015-01-01

    Morphine’s effects on learning and memory processes are well known to depend on synaptic plasticity in the hippocampus. Whereas the role of the hippocampus in morphine-induced amnesia and state-dependent learning is established, the biochemical and molecular mechanisms underlying these processes are poorly understood. The present study intended to investigate whether administration of morphine can change the expression level of rat hippocampal proteins during learning of a passive avoidance task. A step-through type passive avoidance task was used for the assessment of memory retention. To identify the complex pattern of protein expression induced by morphine, we compared rat hippocampal proteome either in morphine-induced amnesia or in state-dependent learning by two-dimensional gel electerophoresis and combined mass spectrometry (MS and MS/MS). Post-training administration of morphine decreased step-through latency. Pre-test administration of morphine induced state-dependent retrieval of the memory acquired under post-training morphine influence. In the hippocampus, a total of 18 proteins were identified whose MASCOT (Modular Approach to Software Construction Operation and Test) scores were inside 95% confidence level. Of these, five hippocampal proteins altered in morphine-induced amnesia and ten proteins were found to change in the hippocampus of animals that had received post-training and pre-test morphine. These proteins show known functions in cytoskeletal architecture, cell metabolism, neurotransmitter secretion and neuroprotection. The findings indicate that the effect of morphine on memory formation in passive avoidance learning has a morphological correlate on the hippocampal proteome level. In addition, our proteomicscreensuggests that morphine induces memory impairment and state-dependent learning through modulating neuronal plasticity. PMID:25901168

  11. [Current state of competence assessment in nursing].

    PubMed

    Darmann-Finck, Ingrid; Reuschenbach, Bernd

    2013-01-01

    Competency measurement is central to the optimisation of outcome oriented educational processes in nursing, similar to the concept of evidence based practice. The classification of measurement tools provides the basis for describing the current state of research and development in relation to competence measurement in nursing science, and any gaps are identified. The article concludes with questioning the importance of outcome oriented quality orientation in order to achieve an increase in quality during training. Further methodological developments and qualitative studies are needed to examine the context specific processes of interaction and learning, beyond competence diagnostics. PMID:23415340

  12. Affinity Proteomics in the mountains: Alpbach 2015.

    PubMed

    Taussig, Michael J

    2016-09-25

    The 2015 Alpbach Workshop on Affinity Proteomics, organised by the EU AFFINOMICS consortium, was the 7th workshop in this series. As in previous years, the focus of the event was the current state of affinity methods for proteome analysis, including complementarity with mass spectrometry, progress in recombinant binder production methods, alternatives to classical antibodies as affinity reagents, analysis of proteome targets, industry focus on biomarkers, and diagnostic and clinical applications. The combination of excellent science with Austrian mountain scenery and winter sports engender an atmosphere that makes this series of workshops exceptional. The articles in this Special Issue represent a cross-section of the presentations at the 2015 meeting. PMID:27118167

  13. [Male contraception - the current state of knowledge].

    PubMed

    Zdrojewicz, Zygmynt; Kasperska, Karolina; Lewandowska, Marta

    2016-08-01

    Contraception is important from a health, psychological and socioeconomic point of view. Due to the fact that male-based contraceptive methods are mostly represented by condoms and vasectomy, researchers are working on the new solutions, which could let the men be more involved in a conscious family planning. In this review we will present the current state of knowledge on this subject. There is a lot going on in the field of hormonal contraception. Studies including testosterone, progestins, synthetic androgens and other derivatives are on a different stages of clinical trials and mostly demonstrate high efficacy rates. Recent discovers of Izumo and Juno proteins, essential for the fertilization process, give hope for an easily reversible, non-hormonal method. Researchers are also trying to interfere with the process of spermatogenesis using BRDT inhibitor - JQ1, or neutralize the sperm by injecting styrene maleic anhydride (SMA) into the lumen of the vas deferens. The other studies explore processes involved in proper sperm motility. A vaccine which induces an immune response to the reproductive system is also an interesting method. The latest research use ultrasound waves and mechanical device which blocks the patency of vas deferens. The aim of the study current state of knowledge male contraception. PMID:27591451

  14. [Male contraception - the current state of knowledge].

    PubMed

    Zdrojewicz, Zygmynt; Kasperska, Karolina; Lewandowska, Marta

    2016-07-01

    Contraception is important from a health, psychological and socioeconomic point of view. Due to the fact that male-based contraceptive methods are mostly represented by condoms and vasectomy, researchers are working on the new solutions, which could let the men be more involved in a conscious family planning. In this review we will present the current state of knowledge on this subject. There is a lot going on in the field of hormonal contraception. Studies including testosterone, progestins, synthetic androgens and other derivatives are on a different stages of clinical trials and mostly demonstrate high efficacy rates. Recent discovers of Izumo and Juno proteins, essential for the fertilization process, give hope for an easily reversible, non-hormonal method. Researchers are also trying to interfere with the process of spermatogenesis using BRDT inhibitor - JQ1, or neutralize the sperm by injecting styrene maleic anhydride (SMA) into the lumen of the vas deferens. The other studies explore processes involved in proper sperm motility. A vaccine which induces an immune response to the reproductive system is also an interesting method. The latest research use ultrasound waves and mechanical device which blocks the patency of vas deferens. The aim of the study current state of knowledge male contraception. PMID:27590656

  15. The Role of Proteomics in the Diagnosis and Treatment of Women's Cancers: Current Trends in Technology and Future Opportunities

    PubMed Central

    Breuer, Eun-Kyoung Yim; Murph, Mandi M.

    2011-01-01

    Technological and scientific innovations over the last decade have greatly contributed to improved diagnostics, predictive models, and prognosis among cancers affecting women. In fact, an explosion of information in these areas has almost assured future generations that outcomes in cancer will continue to improve. Herein we discuss the current status of breast, cervical, and ovarian cancers as it relates to screening, disease diagnosis, and treatment options. Among the differences in these cancers, it is striking that breast cancer has multiple predictive tests based upon tumor biomarkers and sophisticated, individualized options for prescription therapeutics while ovarian cancer lacks these tools. In addition, cervical cancer leads the way in innovative, cancer-preventative vaccines and multiple screening options to prevent disease progression. For each of these malignancies, emerging proteomic technologies based upon mass spectrometry, stable isotope labeling with amino acids, high-throughput ELISA, tissue or protein microarray techniques, and click chemistry in the pursuit of activity-based profiling can pioneer the next generation of discovery. We will discuss six of the latest techniques to understand proteomics in cancer and highlight research utilizing these techniques with the goal of improvement in the management of women's cancers. PMID:21886869

  16. Current Proteomic Methods to Investigate the Dynamics of Histone Turnover in the Central Nervous System.

    PubMed

    Farrelly, L A; Dill, B D; Molina, H; Birtwistle, M R; Maze, I

    2016-01-01

    Characterizing the dynamic behavior of nucleosomes in the central nervous system is vital to our understanding of brain-specific chromatin-templated processes and their roles in transcriptional plasticity. Histone turnover-the complete loss of old, and replacement by new, nucleosomal histones-is one such phenomenon that has recently been shown to be critical for cell-type-specific transcription in brain, synaptic plasticity, and cognition. Such revelations that histones, long believed to static proteins in postmitotic cells, are highly dynamic in neurons were only possible owing to significant advances in analytical chemistry-based techniques, which now provide a platform for investigations of histone dynamics in both healthy and diseased tissues. Here, we discuss both past and present proteomic methods (eg, mass spectrometry, human "bomb pulse labeling") for investigating histone turnover in brain with the hope that such information may stimulate future investigations of both adaptive and aberrant forms of "neuroepigenetic" plasticity. PMID:27423867

  17. Current Proteomic Methods to Investigate the Dynamics of Histone Turnover in the Central Nervous System

    PubMed Central

    Farrelly, L.A.; Dill, B.D.; Molina, H.; Birtwistle, M.R.; Maze, I.

    2016-01-01

    Characterizing the dynamic behavior of nucleosomes in the central nervous system is vital to our understanding of brain-specific chromatin-templated processes and their roles in transcriptional plasticity. Histone turnover—the complete loss of old, and replacement by new, nucleosomal histones—is one such phenomenon that has recently been shown to be critical for cell-type-specific transcription in brain, synaptic plasticity, and cognition. Such revelations that histones, long believed to static proteins in postmitotic cells, are highly dynamic in neurons were only possible owing to significant advances in analytical chemistry-based techniques, which now provide a platform for investigations of histone dynamics in both healthy and diseased tissues. Here, we discuss both past and present proteomic methods (eg, mass spectrometry, human “bomb pulse labeling”) for investigating histone turnover in brain with the hope that such information may stimulate future investigations of both adaptive and aberrant forms of “neuroepigenetic” plasticity. PMID:27423867

  18. Proteome analysis of the Escherichia coli heat shock response under steady-state conditions

    PubMed Central

    Lüders, Svenja; Fallet, Claas; Franco-Lara, Ezequiel

    2009-01-01

    In this study a proteomic approach was used to investigate the steady-state response of Escherichia coli to temperature up-shifts in a cascade of two continuously operated bioreactors. The first reactor served as cell source with optimal settings for microbial growth, while in the second chemostat the cells were exposed to elevated temperatures. By using this reactor configuration, which has not been reported to be used for the study of bacterial stress responses so far, it is possible to study temperature stress under well-defined, steady-state conditions. Specifically the effect on the cellular adaption to temperature stress using two-dimensional gel electrophoresis was examined and compared at the cultivation temperatures of 37°C and 47.5°C. As expected, the steady-state study with the double bioreactor configuration delivered a different protein spectrum compared to that obtained with standard batch experiments in shaking flasks and bioreactors. Setting a high cut-out spot-to-spot size ratio of 5, proteins involved in defence against oxygen stress, functional cell envelope proteins, chaperones and proteins involved in protein biosynthesis, the energy metabolism and the amino acid biosynthesis were found to be differently expressed at high cultivation temperatures. The results demonstrate the complexity of the stress response in a steady-state culture not reported elsewhere to date. PMID:19772559

  19. On the Current Thermal State of Mars.

    NASA Astrophysics Data System (ADS)

    Grott, M.; Breuer, D.

    2008-09-01

    Introduction: The current thermal state of Mars is a fundamental unknown in Mars science. Although is has a huge influence on the planet's current geodynamic activity and controls the possibility for basal melting at the polar caps [1], constraints on this quantities are very scarce. This situation has lately been improved by the study of lithospheric deformation at the north polar cap [2] which constrained the current Martian elastic lithosphere thickness Te, an indirect measure of the temperatures in the planetary interior. Using radar sounding data obtained bySHARAD, the shallow radar onboard the Mars Reconnaissance Orbiter, [2] found that the current Martian lithosphere is extremely stiff and Te is larger than 300 km today. This is surprising as this value is almost twice as large as previously estimated from theoretical considerations and flexure studies [3][1]. In order to be consistent with the planets thermal evolution, [2] argue that the amount of radioactive elements in the Martian interior needs to be subchondritic. This appears to be problematic as geochemical analysis of the SNC meteorites implies higher concentrations of radioactive elements [4]. Furthermore, if the concentration of heat producing elements is indeed reduced, the resulting low interior temperatures will inhibit partial mantle melting and magmatism. However, geological evidence suggests that Mars has been volcanically active in the recent past [5]. In order to address these inconsistencies, we reinvestigate the thermal evolution of Mars and examine its current thermal state for a wide range of initial condition using the current elastic thickness Te and the potential for partial mantle melting to constrain our models. Modeling: We investigate the thermal evolution of Mars by solving the energy balance equations for the core and mantle, treating the mantle energy transport by parametrized convection models. This is done using scaling laws for stagnant lid convection and our model is

  20. Quantitative proteomics analyses of activation states of human THP-1 macrophages.

    PubMed

    Meijer, Kees; Weening, Desiree; de Vries, Marcel P; Priebe, Marion G; Vonk, Roel J; Roelofsen, Han

    2015-10-14

    Macrophages display large functional and phenotypical plasticity. They can adopt a broad range of activation states depending on their microenvironment. Various surface markers are used to characterize these differentially polarized macrophages. However, this is not informative for the functions of the macrophage. In order to have a better understanding of the functional changes of macrophages upon differential polarization, we studied differences in LPS- and IL4-stimulated macrophages. The THP-1 human monocytic cell line, was used as a model system. Cells were labeled, differentiated and stimulated with either LPS or IL-4 in a quantitative SILAC proteomics set-up. The resulting sets of proteins were functionally clustered. LPS-stimulated macrophages show increased secretion of proinflammatory peptides, leading to increased pressure on protein biosynthesis and processing. IL4-stimulated macrophages show upregulation of cell adhesion and extracellular matrix remodeling. Our approach provides an integrated view of polarization-induced functional changes and proves useful for studying functional differences between subsets of macrophages. Moreover, the identified polarization specific proteins may contribute to a better characterization of different activation states in situ and their role in various inflammatory processes. PMID:26200757

  1. Proteomics technology in systems biology.

    PubMed

    Smith, Jeffrey C; Figeys, Daniel

    2006-08-01

    It has now become apparent that a full understanding of a biological process (e.g. a disease state) is only possible if all biomolecular interactions are taken into account. Systems biology works towards understanding the intricacies of cellular life through the collaborative efforts of biologists, chemists, mathematicians and computer scientists and recently, a number of laboratories around the world have embarked upon such research agendas. The fields of genomics and proteomics are foundational in systems biology studies and a great deal of research is currently being conducted in each worldwide. Moreover, many technological advances (particularly in mass spectrometry) have led to a dramatic rise in the number of proteomic studies over the past two decades. This short review summarizes a selection of technological innovations in proteomics that contribute to systems biology studies. PMID:16880956

  2. Biogas production: current state and perspectives.

    PubMed

    Weiland, Peter

    2010-01-01

    Anaerobic digestion of energy crops, residues, and wastes is of increasing interest in order to reduce the greenhouse gas emissions and to facilitate a sustainable development of energy supply. Production of biogas provides a versatile carrier of renewable energy, as methane can be used for replacement of fossil fuels in both heat and power generation and as a vehicle fuel. For biogas production, various process types are applied which can be classified in wet and dry fermentation systems. Most often applied are wet digester systems using vertical stirred tank digester with different stirrer types dependent on the origin of the feedstock. Biogas is mainly utilized in engine-based combined heat and power plants, whereas microgas turbines and fuel cells are expensive alternatives which need further development work for reducing the costs and increasing their reliability. Gas upgrading and utilization as renewable vehicle fuel or injection into the natural gas grid is of increasing interest because the gas can be used in a more efficient way. The digestate from anaerobic fermentation is a valuable fertilizer due to the increased availability of nitrogen and the better short-term fertilization effect. Anaerobic treatment minimizes the survival of pathogens which is important for using the digested residue as fertilizer. This paper reviews the current state and perspectives of biogas production, including the biochemical parameters and feedstocks which influence the efficiency and reliability of the microbial conversion and gas yield. PMID:19777226

  3. Mass spectrometry-based plasma proteomics: state of the art and future outlook.

    PubMed

    Pernemalm, Maria; Lehtiö, Janne

    2014-08-01

    Mass spectrometry-based plasma proteomics is a field where intense research has been performed during the last decade. Being closely linked to biomarker discovery, the field has received a fair amount of criticism, mostly due to the low number of novel biomarkers reaching the clinic. However, plasma proteomics is under gradual development with improvements on fractionation methods, mass spectrometry instrumentation and analytical approaches. These recent developments have contributed to the revival of plasma proteomics. The goal of this review is to summarize these advances, focusing in particular on fractionation methods, both for targeted and global mass spectrometry-based plasma analysis. PMID:24661227

  4. Current state of sewage treatment in China.

    PubMed

    Jin, Lingyun; Zhang, Guangming; Tian, Huifang

    2014-12-01

    The study reported and analyzed the current state of wastewater treatment plants (WWTPs) in urban China from the aspects of scale, treatment processes, sludge handling, geographical distribution, and discharge standards. By 2012, there were 3340 WWTPs in operation in China with a capacity of 1.42 × 10(8) m(3)/d. The number of medium-scale WWTPs (1-10 × 10(4) m(3)/d) counted for 75% of total WWTPs. On average, the chemical oxygen demand (COD) removal efficiencies of small-scale, medium-scale, large-scale and super-large-scale WWTPs were 81, 85.5, 87.5 and 86.5%, respectively. Generally speaking, the nutrients removal instead of COD removal was of concern. As to the different processes, oxidation ditch, anaerobic-anoxic-oxic (A(2)/O) and sequencing batch reactor (SBR) were the mainstream technologies in China. These technologies had minor difference in terms of overall COD removal efficiency. The sludge treatment in WWTPs was basically "thickening-coagulation-mechanical dehydration" and the major disposal method was sanitary landfill in China. The distributions of WWTPs and their utilization showed significant regional characteristics. The sewage treatment capacity of China concentrated on the coastal areas and middle reaches of Yangtze River, which were the economically developed zones. Besides, most WWTPs enforced the Class 1 or Class 2 discharge standards, but few realized wastewater reuse. Finally, existing problems were discussed, including low removal efficiency of nitrogen and phosphorus, emerging contaminants, low reuse of reclaimed water, poor sludge treatment and disposal, low execution standard of effluent, and emissions of greenhouse gas from WWTPs. Suggestions regarding potential technical and administrative measures were given. PMID:25189479

  5. Current state of diagnostic technologies in the autoimmunology laboratory.

    PubMed

    Tozzoli, Renato; Bonaguri, Chiara; Melegari, Alessandra; Antico, Antonio; Bassetti, Danila; Bizzaro, Nicola

    2013-01-01

    The methods for detecting and measuring autoantibodies have evolved markedly in recent years, encompassing three generations of analytical technologies. Many different immunoassay methods have been developed and used for research and laboratory practice purposes, from the early conventional (or monoplex) analytical methods able to detect single autoantibodies to the more recent multiplex platforms that can quantify tens of molecules. Although it has been in use for over 50 years, indirect immunofluorescence remains the standard method for research on many types of autoantibodies, due to its characteristics of diagnostic sensitivity and also to recent technological innovations which permit it a greater level of automation and standardization. The recent multiplex immunometric methods, with varying levels of automation, present characteristics of higher diagnostic accuracy, but are not yet widely diffused in autoimmunology laboratories due to the limited number of autoantibodies that are detectable, and due to the high cost of reagents and systems. Technological advancement in autoimmunology continues to evolve rapidly, and in the coming years new proteomic techniques will be able to radically change the approach to diagnostics and possibly also clinical treatment of autoimmune diseases. The scope of this review is to update the state of the art of technologies and methods for the measurement of autoantibodies, with special reference to innovations in indirect immunofluorescence and in multiple proteomic methods. PMID:23092800

  6. Proteomics of Foodborne Bacterial Pathogens

    NASA Astrophysics Data System (ADS)

    Fagerquist, Clifton K.

    This chapter is intended to be a relatively brief overview of proteomic techniques currently in use for the identification and analysis of microorganisms with a special emphasis on foodborne pathogens. The chapter is organized as follows. First, proteomic techniques are introduced and discussed. Second, proteomic applications are presented specifically as they relate to the identification and qualitative/quantitative analysis of foodborne pathogens.

  7. Embryology in the era of proteomics.

    PubMed

    Katz-Jaffe, M G; Gardner, D K

    2007-09-01

    Currently, relatively little is known regarding the protein production of mammalian embryos. Unlike the genome, the proteome itself is dynamic reflecting both internal and external environmental stimuli. Until now the lack of sensitivity has remained a stumbling block for the global introduction of proteomics into the field of mammalian embryology. However, new developments in mass spectrometry have been revolutionary, utilizing protein profiling and peptide sequencing to elucidate underlying biological processes. The sensitivity of these platforms have allowed for the development of new protocols that are capable of profiling the proteome of individual mammalian oocytes and embryos. This information is fundamental to unravelling the complexity of embryo physiology including the dialogue between the developing embryo and its maternal environment. Such proteomic approaches are also assisting in the optimization of ART techniques, including oocyte cryopreservation and in vitro maturation. Embryo selection for transfer is another area of ART that should benefit in this era of proteomics. Currently, mammalian embryos are selected for transfer based on morphological grading systems. Although of great value, analysis of morphology alone cannot determine the embryo's physiological state or chromosomal complement. Subsequently, there is a need to identify in culture those embryos with the highest implantation potential. Proteomic analysis of the embryonic secretome (proteins produced by the embryo and secreted into the surrounding medium) followed by the identification of specific proteins critical for implantation, may lead to the development of a non-invasive viability assay to assist in the selection of embryos for transfer. PMID:17477967

  8. Proteomics: a subcellular look at spermatozoa

    PubMed Central

    2011-01-01

    Background Male-factor infertility presents a vexing problem for many reproductively active couples. Many studies have focused on abnormal sperm parameters. Recent advances in proteomic techniques, especially in mass spectrometry, have aided in the study of sperm and more specifically, sperm proteins. The aim of this study was to review the current literature on the various proteomic techniques, and their usefulness in diagnosing sperm dysfunction and potential applications in the clinical setting. Methods Review of PubMed database. Key words: spermatozoa, proteomics, protein, proteome, 2D-PAGE, mass spectrometry. Results Recently employed proteomic methods, such as two-dimensional polyacrylamide gel electrophoresis, mass spectrometry, and differential in gel electrophoresis, have identified numerous sperm-specific proteins. They also have provided a further understanding of protein function involved in sperm processes and for the differentiation between normal and abnormal states. In addition, studies on the sperm proteome have demonstrated the importance of post-translational modifications, and their ability to bring about physiological changes in sperm function. No longer do researchers believe that in order for them to elucidate the biochemical functions of genes, mere knowledge of the human genome sequence is sufficient. Moreover, a greater understanding of the physiological function of every protein in the tissue-specific proteome is essential in order to unravel the biological display of the human genome. Conclusion Recent advances in proteomic techniques have provided insight into sperm function and dysfunction. Several multidimensional separation techniques can be utilized to identify and characterize spermatozoa. Future developments in bioinformatics can further assist researchers in understanding the vast amount of data collected in proteomic studies. Moreover, such advances in proteomics may help to decipher metabolites which can act as biomarkers in

  9. Fish Vaccines: Current State and Future Advances

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In aquaculture, the development and use of vaccines is now making rapid progress to achieve its full potential as an effective disease prevention tool. Currently, USDA, APHIS, CVB licenses 17 fish vaccines of which 2 are modified live and 14 are killed vaccines. The objective of vaccination is to pr...

  10. Current State of Clostridium difficile Treatment Options

    PubMed Central

    Venugopal, Anilrudh A.; Johnson, Stuart

    2012-01-01

    Recent reports of reduced response to standard therapies for Clostridium difficile infection (CDI) and the risk for recurrent CDI that is common with all currently available treatment agents have posed a significant challenge to clinicians. Current recommendations include metronidazole for treatment of mild to moderate CDI and vancomycin for severe CDI. Results from small clinical trials suggest that nitazoxanide and teicoplanin may be alternative options to standard therapies, whereas rifaximin has demonstrated success in uncontrolled trials for the management of multiple recurrences. Anecdotal reports have also suggested that tigecycline might be useful as an adjunctive agent for the treatment of severe complicated CDI. Reports of resistance will likely limit the clinical use of fusidic acid and bacitracin and, possibly, rifaximin if resistance to this agent becomes widespread. Treatment of patients with multiple CDI recurrences and those with severe complicated CDI is based on limited clinical evidence, and new treatments or strategies are needed. PMID:22752868

  11. Digital mammography: current state and future aspects.

    PubMed

    Fischer, U; Hermann, K P; Baum, F

    2006-01-01

    The introduction of digital technique in mammography has been the last step in completing the process of digitalization in diagnostic imaging. Meanwhile, some different digital techniques as well as a couple of different digital mammography systems were developed and have already been available for some years. In this review article, the relevant data of key studies are reported, the current status is defined, and perspectives of digital mammography are described. PMID:16132935

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

    SciTech Connect

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

    2012-08-31

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

  13. State Profiles: Current Status of Public Sector Labor Relations.

    ERIC Educational Resources Information Center

    Labor Management Services Administration (DOL), Washington, DC. Div. of Public Employee Labor Relations.

    This guide summarizes the coverage of public employees by state labor relations laws. For each state, the guide describes legal provisions, current situation, and current legislative activity. The report also includes data on population, public employment, work stoppages, and state revenues and expenditures. Agencies useful in gathering and…

  14. Bi-layer steady state current cloak

    NASA Astrophysics Data System (ADS)

    Zeng, Lunwu

    2014-02-01

    We report that bi-layer copper and polystyrene cylinders can cloak steady current. We fabricated two hollow cylinders, the one made of copper, and the other made of polystyrene. Two hollow copper and polystyrene cylinders nested concentric bi-layer hollow copper and polystyrene cylinders. The background media are made of aluminum. Theory and experiment demonstrated that the electric potential gradients are parallel and equal outside the outer circle, the iso-potential lines are parallel outside the outer circle, and the electric potential is zero in the inner circle.

  15. Application of meta-transcriptomics and -proteomics to analysis of in situ physiological state

    SciTech Connect

    Konopka, Allan; Wilkins, Michael J.

    2012-05-18

    Analysis of the growth-limiting factor or environmental stressors affecting microbes in situ is of fundamental importance but analytically difficult. Microbes can reduce in situ limiting nutrient concentrations to sub-micromolar levels, and contaminated ecosystems may contain multiple stressors. The patterns of gene or protein expression by microbes in nature can be used to infer growth limitations, because they are regulated in response to environmental conditions. Experimental studies under controlled conditions in the laboratory provide the physiological underpinnings for developing these physiological indicators. Although regulatory networks may differ among specific microbes, there are some broad principles that can be applied, related to limiting nutrient acquisition, resource allocation, and stress responses. As technologies for transcriptomics and proteomics mature, the capacity to apply these approaches to complex microbial communities will accelerate. Global proteomics has the particular advantage that it reflects expressed catalytic activities. Furthermore, the high mass accuracy of some proteomic approaches allows mapping back to specific microbial strains. For example, at the Rifle IFRC field site in Western Colorado, the physiological status of Fe(III)-reducing populations has been tracked over time. Members of a 'subsurface clade' within the Geobacter predominated during carbon amendment to the subsurface environment. At the functional level, proteomic identifications produced inferences regarding (i) temporal changes in anabolism and catabolism of acetate, (ii) the onset of N2 fixation when N became limiting, and (iii) expression of phosphate transporters during periods of intense growth. The application of these approaches in situ can lead to discovery of novel physiological adaptations.

  16. Spaceflight osteoporosis: current state and future perspective.

    PubMed

    Cappellesso, R; Nicole, L; Guido, A; Pizzol, D

    2015-10-01

    Osteoporosis is one of the established major consequences of long-duration spaceflights in astronauts seriously undermining their health after their returning on Earth. Indeed, astronauts typically lose more bone mass during one month than postmenopausal women on Earth lose in one year. To date, countermeasures mainly consist in exercise and supplementation while pharmacological treatment as those used in postmenopausal women are not routine. However, it is evident that exercise and supplementation alone are not enough to maintain bone homeostasis. In this paper we describe the current countermeasures for bone loss during long-term spaceflight, review the modern treatment which are successfully employed to prevent osteoporosis on Earth and that could be quickly used also for astronauts and finally focus on the recent cellular and molecular understanding of bone homeostasis which might provide the basis for the development of future targeted therapies. PMID:26494042

  17. Current State of Opioid Therapy and Abuse.

    PubMed

    Manchikanti, Laxmaiah; Kaye, Adam M; Kaye, Alan D

    2016-05-01

    Currently, there is growing tension between the twin challenges of opioid therapy for chronic pain and adverse consequences of abuse, leading to multiple complications including respiratory failure and death. The recent data from Centers for Disease Control and Prevention (CDC) have shown continued escalation of prescription opioid use with opioid overdose deaths topping all previous estimations. Numerous policy initiatives, advisories, and guidelines have been advanced through the years to control the opioid epidemic. The strategies to prevent opioid abuse and to maintain opioid therapy when medically necessary fall into primary and secondary prevention categories. The primary prevention category is extremely crucial, since it involves education of primary care providers and patients at the starting point of opioid therapy. The education of surgeons and other prescribers is as crucial as the education of primary care physicians. PMID:27048483

  18. Current state of imaging in dermatology.

    PubMed

    Hibler, Brian P; Qi, Qiaochu; Rossi, Anthony M

    2016-03-01

    Medical imaging has dramatically transformed the practice of medicine, especially the field of dermatology. Imaging is used to facilitate the transfer of information between providers, document cutaneous disease, assess response to therapy, and plays a crucial role in monitoring and diagnosing skin cancer. Advancements in imaging technology and overall improved quality of imaging have augmented the utility of photography. We provide an overview of current imaging technologies used in dermatology with a focus on their role in skin cancer diagnosis. Future technologies include three-dimensional, total-body photography, mobile smartphone applications, and computerassisted diagnostic devices. With these advancements, we are better equipped to capture and monitor skin conditions longitudinally and achieve improved diagnostic accuracy of skin cancer. PMID:26963110

  19. The current state of Socio-hydrology

    NASA Astrophysics Data System (ADS)

    Sivapalan, Murugesu; Viglione, Alberto; Di Baldassarre, Giuliano; Pande, Saket

    2016-04-01

    Socio-hydrology was introduced 4 years ago into the scientific lexicon, and elicited several reactions about the meaning and originality of the concept. However, there has also been much activity triggered by the original paper, including further commentaries that clarified the definitions, and several papers that acted on the definitions, and through them further clarified and illustrated the meaning and usefulness of socio-hydrology for understanding coupled human-water systems and underpinning sustainable water management. This presentation discusses how useful these recent studies have been towards the need for socio-hydrology to explain phenomena, such as rise and decline of human population or food production in water scarce basins ('pendulum swing'), the levee effect, small scale farmer suicides, anthropogenic droughts, etc… We also discuss its foundation as a Science, its similarities and dissimilarities with other fields that study human-water interactions, such as hydro-sociology and hydro-economics, its foundation as a Science, current gaps and the challenges that lie ahead.

  20. Current state of cardiac rehabilitation in Japan.

    PubMed

    Goto, Yoichi

    2014-01-01

    In Japan, metabolic risk factors have been increasing due to the westernization and urbanization of lifestyle. This justifiably raises a concern that the incidence of coronary heart disease (CHD) in Japan will increase over time, and indeed, recent epidemiological studies in Japan suggest the incidence of acute myocardial infarction (AMI) is increasing. Cardiac rehabilitation (CR) in Japan has been traditionally performed in the inpatient setting. To obtain reimbursement, a CR facility must fulfill certain criteria including being a medical institution with a cardiology/cardiac surgery section which has at least a cardiologist/cardiac surgeon and an experienced CR physician as full-time employees. These criteria create challenges to the availability of outpatient CR after hospital discharge. A recent analysis found outpatient CR participation rate was estimated to be between 3.8 and 7.6% in Japan. This review describes recent trends in the incidence of AMI and the current status of the use of CR in Japan. PMID:24607022

  1. ECLAIRs detection plane: current state of development

    NASA Astrophysics Data System (ADS)

    Lacombe, K.; Pons, R.; Amoros, C.; Atteia, J.-L.; Barret, D.; Billot, M.; Bordon, S.; Cordier, B.; Gevin, O.; Godet, O.; Gonzalez, F.; Houret, B.; Mercier, K.; Mandrou, P.; Marty, W.; Nasser, G.; Rambaud, D.; Ramon, P.; Rouaix, G.; Waegebaert, V.

    2014-07-01

    ECLAIRs, a 2-D coded-mask imaging camera on-board the Sino-French SVOM space mission, will detect and locate Gamma-ray bursts (GRBs) in near real time in the 4-150 keV energy band. The design of ECLAIRs has been mainly driven by the objective of achieving a low-energy threshold of 4 keV, unprecedented for this type of instrument. The detection plane is an assembly of 6400 Schottky CdTe semiconductor detectors of size 4x4x1 mm3 organized on elementary hybrid matrices of 4x8 detectors. The detectors will be polarized from -300V to -500V and operated at -20°C to reduce both the leakage current and the polarization effect induced by the Schottky contact. The remarkable low-energy threshold homogeneity required for the detection plane has been achieved thanks to: i) an extensive characterization and selection of the detectors, ii) the development of a specific low-noise 32-channel ASIC, iii) the realization of an innovative hybrid module composed of a thick film ceramic (holding 32 CdTe detectors with their high voltage grid), associated to an HTCC ceramic (housing the ASIC chip within an hermetic enclosure). In this paper, we start describing a complete hybrid matrix, and then the manufacturing of a first set of 50 matrices (representing 1600 detectors, i.e. a quarter of ECLAIRs detector's array). We show how this manufacturing allowed to validate the different technologies used for this hybridization, as well as the industrialization processes. During this phase, we systematically measured the leakage current on Detector Ceramics after an outgassing, and the Equivalent Noise Charge (ENC) for each of the 32 channels on ASIC Ceramics, in order to optimize the coupling of the two ceramics. Finally, we performed on each hybrid module, spectral measurements at -20°C in our vacuum chamber, using several calibrated radioactive sources (241Am and 55Fe), to check the performance homogeneity of the 50 modules. The results demonstrated that the 32-detector hybrid matrices

  2. Application of meta-transcriptomics and -proteomics to analysis of in situ physiological state

    PubMed Central

    Konopka, Allan; Wilkins, Michael J.

    2012-01-01

    Analysis of the growth-limiting factor or environmental stressors affecting microbes in situ is of fundamental importance but analytically difficult. Microbes can reduce in situ limiting nutrient concentrations to sub-micromolar levels, and contaminated ecosystems may contain multiple stressors. The patterns of gene or protein expression by microbes in nature can be used to infer growth limitations, because they are regulated in response to environmental conditions. Experimental studies under controlled conditions in the laboratory provide the physiological underpinnings for developing these physiological indicators. Although regulatory networks may differ among specific microbes, there are some broad principles that can be applied, related to limiting nutrient acquisition, resource allocation, and stress responses. As technologies for transcriptomics and proteomics mature, the capacity to apply these approaches to complex microbial communities will accelerate. Global proteomics has the particular advantage that it reflects expressed catalytic activities. Furthermore, the high mass accuracy of some proteomic approaches allows mapping back to specific microbial strains. For example, at the Rifle IFRC field site in Western Colorado, the physiological status of Fe(III)-reducing populations has been tracked over time. Members of a “subsurface clade” within the Geobacter predominated during carbon amendment to the subsurface environment. At the functional level, proteomic identifications produced inferences regarding (i) temporal changes in anabolism and catabolism of acetate, (ii) the onset of N2 fixation when N became limiting, and (iii) expression of phosphate transporters during periods of intense growth. The application of these approaches in situ can lead to discovery of novel physiological adaptations. PMID:22783237

  3. Ion Current-Based Proteomic Profiling for Understanding the Inhibitory Effect of Tumor Necrosis Factor Alpha on Myogenic Differentiation.

    PubMed

    Tu, Chengjian; Bu, Yahao; Vujcic, Marija; Shen, Shichen; Li, Jun; Qu, Miao; Hangauer, David; Clements, James L; Qu, Jun

    2016-09-01

    Despite a demonstrated role for TNF-α in promoting muscle wasting and cachexia, the associated molecular mechanisms and signaling pathways of myoblast differentiation dysregulated by TNF-α remain poorly understood. This study presents well-controlled proteomic profiling as a means to investigate the mechanisms of TNF-α-regulated myogenic differentiation. Primary human muscle precursor cells (MPCs) cultured in growth medium (GM), differentiation medium (DM) to induce myogenic differentiation, and DM with 20 ng/mL of TNF-α (n = 5/group) were comparatively analyzed by an ion current-based quantitative platform consisting of reproducible sample preparation/on-pellet digestion, a long-column nano-LC separation, and ion current-based differential analysis. The inhibition of myogenic differentiation by TNF-α was confirmed by reduced formation of multinucleated myotubes and the recovered expression of altered myogenic proteins such as MYOD and myogenin during myogenic differentiation. Functional analysis and validation by immunoassay analysis suggested that the cooperation of NF-κB and STAT proteins is responsible for dysregulated differentiation in MPCs by TNF-α treatment. Increased MHC class I components such as HLA-A, HLA-B, HLA-C, and beta-2-microglobulin were also observed in cultures in DM treated with TNF-α. Interestingly, inhibition of the cholesterol biosynthesis pathway during myogenic differentiation induced by serum starvation was not recovered by TNF-α treatment, which combined with previous reports, implies that this process may be an early event of myogenesis. This finding could lay the foundation for the potential use of statins in modulating myogenesis through cholesterol, for example, in stem cell-based myocardial infarction treatment, where differentiation of myoblasts and stem cells into force-generating mature muscle cells is a key step to the therapeutic capacity. In conclusion, the landscapes of altered transcription regulators, metabolic

  4. Quantum backflow states from eigenstates of the regularized current operator

    NASA Astrophysics Data System (ADS)

    Halliwell, J. J.; Gillman, E.; Lennon, O.; Patel, M.; Ramirez, I.

    2013-11-01

    We present an exhaustive class of states with quantum backflow—the phenomenon in which a state consisting entirely of positive momenta has negative current and the probability flows in the opposite direction to the momentum. They are characterized by a general function of momenta subject to very weak conditions. Such a family of states is of interest in the light of a recent experimental proposal to measure backflow. We find one particularly simple state which has surprisingly large backflow—about 41% of the lower bound on flux derived by Bracken and Melloy. We study the eigenstates of a regularized current operator and we show how some of these states, in a certain limit, lead to our class of backflow states. This limit also clarifies the correspondence between the spectrum of the regularized current operator, which has just two non-zero eigenvalues in our chosen regularization, and the usual current operator.

  5. Reproducible ion-current-based approach for 24-plex comparison of the tissue proteomes of hibernating versus normal myocardium in swine models.

    PubMed

    Qu, Jun; Young, Rebeccah; Page, Brian J; Shen, Xiaomeng; Tata, Nazneen; Li, Jun; Duan, Xiaotao; Fallavollita, James A; Canty, John M

    2014-05-01

    Hibernating myocardium is an adaptive response to repetitive myocardial ischemia that is clinically common, but the mechanism of adaptation is poorly understood. Here we compared the proteomes of hibernating versus normal myocardium in a porcine model with 24 biological replicates. Using the ion-current-based proteomic strategy optimized in this study to expand upon previous proteomic work, we identified differentially expressed proteins in new molecular pathways of cardiovascular interest. The methodological strategy includes efficient extraction with detergent cocktail; precipitation/digestion procedure with high, quantitative peptide recovery; reproducible nano-LC/MS analysis on a long, heated column packed with small particles; and quantification based on ion-current peak areas. Under the optimized conditions, high efficiency and reproducibility were achieved for each step, which enabled a reliable comparison of 24 the myocardial samples. To achieve confident discovery of differentially regulated proteins in hibernating myocardium, we used highly stringent criteria to define "quantifiable proteins". These included the filtering criteria of low peptide FDR and S/N > 10 for peptide ion currents, and each protein was quantified independently from ≥2 distinct peptides. For a broad methodological validation, the quantitative results were compared with a parallel, well-validated 2D-DIGE analysis of the same model. Excellent agreement between the two orthogonal methods was observed (R = 0.74), and the ion-current-based method quantified almost one order of magnitude more proteins. In hibernating myocardium, 225 significantly altered proteins were discovered with a low false-discovery rate (∼3%). These proteins are involved in biological processes including metabolism, apoptosis, stress response, contraction, cytoskeleton, transcription, and translation. This provides compelling evidence that hibernating myocardium adapts to chronic ischemia. The major metabolic

  6. Proteomics research in India: an update.

    PubMed

    Reddy, Panga Jaipal; Atak, Apurva; Ghantasala, Saicharan; Kumar, Saurabh; Gupta, Shabarni; Prasad, T S Keshava; Zingde, Surekha M; Srivastava, Sanjeeva

    2015-09-01

    After a successful completion of the Human Genome Project, deciphering the mystery surrounding the human proteome posed a major challenge. Despite not being largely involved in the Human Genome Project, the Indian scientific community contributed towards proteomic research along with the global community. Currently, more than 76 research/academic institutes and nearly 145 research labs are involved in core proteomic research across India. The Indian researchers have been major contributors in drafting the "human proteome map" along with international efforts. In addition to this, virtual proteomics labs, proteomics courses and remote triggered proteomics labs have helped to overcome the limitations of proteomics education posed due to expensive lab infrastructure. The establishment of Proteomics Society, India (PSI) has created a platform for the Indian proteomic researchers to share ideas, research collaborations and conduct annual conferences and workshops. Indian proteomic research is really moving forward with the global proteomics community in a quest to solve the mysteries of proteomics. A draft map of the human proteome enhances the enthusiasm among intellectuals to promote proteomic research in India to the world.This article is part of a Special Issue entitled: Proteomics in India. PMID:25868663

  7. The State of the Human Proteome in 2013 as viewed through PeptideAtlas: Comparing the Kidney, Urine, and Plasma Proteomes for the Biology and Disease-driven Human Proteome Project

    PubMed Central

    Farrah, Terry; Deutsch, Eric W.; Omenn, Gilbert S.; Sun, Zhi; Watts, Julian D.; Yamamoto, Tadashi; Shteynberg, David; Harris, Micheleen M.; Moritz, Robert L.

    2014-01-01

    The kidney, urine, and plasma proteomes are intimately related: proteins and metabolic waste products are filtered from the plasma by the kidney and excreted via the urine, while kidney proteins may be secreted into the circulation or released into the urine. Shotgun proteomics datasets derived from human kidney, urine, and plasma samples were collated and processed using a uniform software pipeline, and relative protein abundances were estimated by spectral counting. The resulting PeptideAtlas builds yielded 4005, 2491, and 3553 nonredundant proteins at 1% FDR for the kidney, urine, and plasma proteomes, respectively—for kidney and plasma, the largest high-confidence protein sets to date. The same pipeline applied to all available human data yielded a 2013 Human PeptideAtlas build containing 12,644 nonredundant proteins and at least one peptide for each of ~14,000 Swiss-Prot entries, an increase over 2012 of ~7.5% of the predicted human proteome. We demonstrate that abundances are correlated between plasma and urine, examine the most abundant urine proteins not derived from either plasma or kidney, and consider the biomarker potential of proteins associated with renal decline. This analysis forms part of the Biology and Disease-driven Human Proteome Project (B/D-HPP) and a contribution to the Chromosome-centric Human Proteome Project (C-HPP) special issue. PMID:24261998

  8. Proteins interacting with monoamine transporters: current state and future challenges.

    PubMed

    Sager, Jonathan J; Torres, Gonzalo E

    2011-08-30

    Plasma membrane and vesicular transporters for the biogenic amines, dopamine, norepinephrine, and serotonin, represent a group of proteins that play a crucial role in the regulation of neurotransmission. Clinically, mono amine transporters are the primary targets for the actions of many therapeutic agents used to treat mood disorders, as well as the site of action for highly addictive psychostimulants such as cocaine, amphetamine, methamphetamine, and 3,4-methylenedioxymethamphetamine. Over the past decade, the use of approaches such as yeast two-hybrid and proteomics has identified a multitude of transporter interacting proteins, suggesting that the function and regulation of these transporters are more complex than previously anticipated. With the increasing number of interacting proteins, the rules dictating transporter synthesis, assembly, targeting, trafficking, and function are beginning to be deciphered. Although many of these protein interactions have yet to be fully characterized, current knowledge is beginning to shed light on novel transporter mechanisms involved in monoamine homeostasis, the molecular actions of psychostimulants, and potential disease mechanisms. While future studies resolving the spatial and temporal resolution of these, and yet unknown, interactions will be needed, the realization that monoamine transporters do not work alone opens the path to a plethora of possible pharmacological interventions. PMID:21797260

  9. Low T3 State Is Correlated with Cardiac Mitochondrial Impairments after Ischemia Reperfusion Injury: Evidence from a Proteomic Approach

    PubMed Central

    Forini, Francesca; Ucciferri, Nadia; Kusmic, Claudia; Nicolini, Giuseppina; Cecchettini, Antonella; Rocchiccioli, Silvia; Citti, Lorenzo; Iervasi, Giorgio

    2015-01-01

    Mitochondria are major determinants of cell fate in ischemia/reperfusion injury (IR) and common effectors of cardio-protective strategies in cardiac ischemic disease. Thyroid hormone homeostasis critically affects mitochondrial function and energy production. Since a low T3 state (LT3S) is frequently observed in the post infarction setting, the study was aimed to investigate the relationship between 72 h post IR T3 levels and both the cardiac function and the mitochondrial proteome in a rat model of IR. The low T3 group exhibits the most compromised cardiac performance along with the worst mitochondrial activity. Accordingly, our results show a different remodeling of the mitochondrial proteome in the presence or absence of a LT3S, with alterations in groups of proteins that play a key role in energy metabolism, quality control and regulation of cell death pathways. Overall, our findings highlight a relationship between LT3S in the early post IR and poor cardiac and mitochondrial outcomes, and suggest a potential implication of thyroid hormone in the cardio-protection and tissue remodeling in ischemic disease. PMID:26561807

  10. Theory of current states in narrow superconducting channels

    SciTech Connect

    Ivlev, B.I.; Kopnin, N.B.

    1984-03-01

    The properties of narrow superconducting channels carrying a direct current are reviewed. Among the topics covered are the stability of the normal state of the current-carrying channel and the mechanism for a transition from this normal state to the superconducting state. In a homogeneous channel, the transition occurs through the formation of a critical nucleus and is a first-order phase transition. In a channel with inhomogeneities, the transition is quite different. In this case the normal state can exist only down to a certain value of the current, below which the normal state is absolutely unstable. The review is devoted primarily to the theory of the resistive state of narrow channels, which exists at currents above the critical Ginzburg-Landau current. The description is based on the concept of phase-slippage centers. Phenomenological models are discussed, as is a model of a fluctuational excitation of phase-slippage centers. The results obtained from the microscopic dynamic theory of superconductivity are discussed at length. Among these results are the voltage-current characteristic of the resistive state, the abrupt change in the voltage on this characteristic, and the structure of the phase-slippage centers.

  11. Postgenomics: Proteomics and Bioinformatics in Cancer Research

    PubMed Central

    2003-01-01

    Now that the human genome is completed, the characterization of the proteins encoded by the sequence remains a challenging task. The study of the complete protein complement of the genome, the “proteome,” referred to as proteomics, will be essential if new therapeutic drugs and new disease biomarkers for early diagnosis are to be developed. Research efforts are already underway to develop the technology necessary to compare the specific protein profiles of diseased versus nondiseased states. These technologies provide a wealth of information and rapidly generate large quantities of data. Processing the large amounts of data will lead to useful predictive mathematical descriptions of biological systems which will permit rapid identification of novel therapeutic targets and identification of metabolic disorders. Here, we present an overview of the current status and future research approaches in defining the cancer cell's proteome in combination with different bioinformatics and computational biology tools toward a better understanding of health and disease. PMID:14615629

  12. Proteomic Technologies for the Study of Osteosarcoma

    PubMed Central

    Byrum, Stephanie D.; Washam, Charity L.; Montgomery, Corey O.; Tackett, Alan J.; Suva, Larry J.

    2012-01-01

    Osteosarcoma is the most common primary bone cancer of children and is established during stages of rapid bone growth. The disease is a consequence of immature osteoblast differentiation, which gives way to a rapidly synthesized incompletely mineralized and disorganized bone matrix. The mechanism of osteosarcoma tumorogenesis is poorly understood, and few proteomic studies have been used to interrogate the disease thus far. Accordingly, these studies have identified proteins that have been known to be associated with other malignancies, rather than being osteosarcoma specific. In this paper, we focus on the growing list of available state-of-the-art proteomic technologies and their specific application to the discovery of novel osteosarcoma diagnostic and therapeutic targets. The current signaling markers/pathways associated with primary and metastatic osteosarcoma that have been identified by early-stage proteomic technologies thus far are also described. PMID:22550414

  13. Proteomics for systems toxicology

    PubMed Central

    Titz, Bjoern; Elamin, Ashraf; Martin, Florian; Schneider, Thomas; Dijon, Sophie; Ivanov, Nikolai V.; Hoeng, Julia; Peitsch, Manuel C.

    2014-01-01

    Current toxicology studies frequently lack measurements at molecular resolution to enable a more mechanism-based and predictive toxicological assessment. Recently, a systems toxicology assessment framework has been proposed, which combines conventional toxicological assessment strategies with system-wide measurement methods and computational analysis approaches from the field of systems biology. Proteomic measurements are an integral component of this integrative strategy because protein alterations closely mirror biological effects, such as biological stress responses or global tissue alterations. Here, we provide an overview of the technical foundations and highlight select applications of proteomics for systems toxicology studies. With a focus on mass spectrometry-based proteomics, we summarize the experimental methods for quantitative proteomics and describe the computational approaches used to derive biological/mechanistic insights from these datasets. To illustrate how proteomics has been successfully employed to address mechanistic questions in toxicology, we summarized several case studies. Overall, we provide the technical and conceptual foundation for the integration of proteomic measurements in a more comprehensive systems toxicology assessment framework. We conclude that, owing to the critical importance of protein-level measurements and recent technological advances, proteomics will be an integral part of integrative systems toxicology approaches in the future. PMID:25379146

  14. Visualization and data analysis-current state and exascale challenges

    SciTech Connect

    Ahrens, James P; Rodgers, David; Springmeyer, Becky

    2010-12-21

    Talk about Visualization and Data Analysis Current State and Exascale challenges. The goal is to update with colleagues our current status in our research. What challenges we need to face, and what future possibilities. Our goal is to propose to approach the problems with the visualization approach operating on the supercomputing platform. This presentation is about the L2 Milestone, we intend to discuss further possibilities of enhancing our results and optimizing our solutions.

  15. The Current State of Biomarkers in Systemic Sclerosis

    PubMed Central

    2010-01-01

    Scleroderma is a complex, multisystem autoimmune rheumatic disease with wide heterogeneity in phenotype and outcome. There are often coexisting ongoing pathologic processes including immune system activation, progressive fibrosis, and vascular disease in subsets of patients. Currently, it is challenging to identify patients at risk for developing adverse outcomes and to determine which patients are responding to current therapies. For these reasons, it is highly valuable to find easily measurable biomarkers that may represent ongoing disease activity or treatment response. This review examines the current state of biomarker development in systemic sclerosis and identifies areas in which further work should be directed. PMID:20425531

  16. Current state of care for diabetic retinopathy in India.

    PubMed

    Ramasamy, Kim; Raman, Rajiv; Tandon, Manish

    2013-08-01

    In this article we review the current state of care of diabetic retinopathy in India. We discuss the magnitude of the problem; diabetes, and diabetic retinopathy in India. We highlight the causes of vision loss in diabetic retinopathy. The current level of awareness among general population and physicians is a concern. Current screening strategies practiced in India and the situational analysis of ophthalmologists in India are also reviewed. We review the current management of diabetic macular edema and proliferative diabetic retinopathy. To know the current practice pattern among retinal surgeons in India, a survey was done and the results of the survey are presented. There are few studies in the Indian population which have found some genetic risk and protective factors and a summary of these studies are also presented in this article. PMID:23657764

  17. Coupling enrichment methods with proteomics for understanding and treating disease.

    PubMed

    Kumar, Amit; Baycin-Hizal, Deniz; Shiloach, Joseph; Bowen, Michael A; Betenbaugh, Michael J

    2015-02-01

    Owing to recent advances in proteomics analytical methods and bioinformatics capabilities there is a growing trend toward using these capabilities for the development of drugs to treat human disease, including target and drug evaluation, understanding mechanisms of drug action, and biomarker discovery. Currently, the genetic sequences of many major organisms are available, which have helped greatly in characterizing proteomes in model animal systems and humans. Through proteomics, global profiles of different disease states can be characterized (e.g. changes in types and relative levels as well as changes in PTMs such as glycosylation or phosphorylation). Although intracellular proteomics can provide a broad overview of physiology of cells and tissues, it has been difficult to quantify the low abundance proteins which can be important for understanding the diseased states and treatment progression. For this reason, there is increasing interest in coupling comparative proteomics methods with subcellular fractionation and enrichment techniques for membranes, nucleus, phosphoproteome, glycoproteome as well as low abundance serum proteins. In this review, we will provide examples of where the utilization of different proteomics-coupled enrichment techniques has aided target and biomarker discovery, understanding the drug targeting mechanism, and mAb discovery. Taken together, these improvements will help to provide a better understanding of the pathophysiology of various diseases including cancer, autoimmunity, inflammation, cardiovascular disease, and neurological conditions, and in the design and development of better medicines for treating these afflictions. PMID:25523641

  18. The Current State of Marketing Activity among Higher Education Institutions.

    ERIC Educational Resources Information Center

    Newman, Cynthia M.

    2002-01-01

    Investigated the current state of marketing, marketing research, and planning practices at four-year higher education institutions. Builds upon previous studies by Blackburn (1979) and Goldgehn (1982 and 1989). Determined whether the use and apparent understanding of marketing and its attendant activities by admissions and enrollment management…

  19. Current density and state density in diluted magnetic semiconductor nanostructures

    NASA Astrophysics Data System (ADS)

    Pérez Merchancano, S. T.; Paredes Gutiérrez, H.; Zuñiga, J. A.

    2016-02-01

    We study in this paper the spin-polarized current density components in diluted magnetic semiconductor tunnelling diodes with different sample geometries. We calculate the resonant JxV and the density of states. The differential conductance curves are analyzed as functions of the applied voltage and the magnetic potential strength induced by the magnetic ions.

  20. Trends in State Coordination and Governance: Historical and Current Perspectives.

    ERIC Educational Resources Information Center

    Epper, Rhonda Martin; Russell, Alene Bycer

    This report examines the roles and functions of state coordinating and governing boards of higher education. Data are from a study reviewing 20 years' worth of data and a current survey. After an introductory section, the first section analyzes historical trends which suggest modest growth in appropriations over the period. Section 2, based on the…

  1. The Current State of Predicting Furrow Irrigation Erosion

    Technology Transfer Automated Retrieval System (TEKTRAN)

    There continues to be a need to predict furrow irrigation erosion to estimate on- and off-site impacts of irrigation management. The objective of this paper is to review the current state of furrow erosion prediction technology considering four models: SISL, WEPP, WinSRFR and APEX. SISL is an empiri...

  2. Current Sensor Based Home Appliance and State of Appliance Recognition

    NASA Astrophysics Data System (ADS)

    Saitoh, Takeshi; Osaki, Tomoyuki; Konishi, Ryosuke; Sugahara, Kazunori

    This paper presents a current sensor-based home appliance and its state recognition method for intelligent outlets. Our system has three main functions: remote control, monitoring, and power supply schedule management. This research focuses particular on the monitoring function. To recognize the appliance and the state of the appliance, we extract ten features based on a measured current signal. In the experiment, we gather a number of signals with various appliances, and find that three features Irms, Iavg, and Ipeak yield valid recognition results of 84.3%, 86.4%, and 90.3% for classifying the state of the appliance into three categories. Moreover, sufficient recognition rates of 97.4%, 97.7%, and 99.0% are obtained by consideration of three candidates.

  3. Current Major Depression Among Smokers Using a State Quitline

    PubMed Central

    Hebert, Kiandra K.; Cummins, Sharon E.; Hernandez, Sandra; Tedeschi, Gary J.; Zhu, Shu-Hong

    2010-01-01

    Background Smokers seeking treatment to quit smoking are generally not assessed for current depression, yet depression among smokers may influence quitting outcome. Purpose This study aims to formally assess current major depression among smokers calling a state tobacco quitline. Methods A total of 844 smokers calling the California Smokers’ Helpline in 2007 were screened for depression by the mood module of the Patient Health Questionnaire (PHQ-9). The Social Functioning Questionnaire (SFQ) was also administered to these callers. Two months after the screening, follow-up evaluations were conducted to assess cessation outcome. Results In all, 24.2% of smokers met criteria for current major depression and 16.5% reported symptoms indicating mild depression. Callers with current major depression were more likely to be heavy smokers and on Medicaid. Moreover, 74.0% of smokers with current major depression had substantial social and occupational functioning deficits. Two months later, those with major depression at baseline were significantly less likely to have quit smoking (18.5% vs 28.4%). Conclusions Almost one in four smokers to the California Smokers’ Helpline met criteria for current major depression. Over 400,000 smokers call state quitlines in the U.S. for help with quitting each year, which means that as many as 100,000 smokers with serious depressive symptoms are using these services annually. The large number of depressed smokers who seek help suggests a need to develop appropriate interventions to help them quit successfully. PMID:21146767

  4. Proteomic analysis of temperature dependent extracellular proteins from Aspergillus fumigatus grown under solid-state culture condition.

    PubMed

    Adav, Sunil S; Ravindran, Anita; Sze, Siu Kwan

    2013-06-01

    Fungal species of the genus Aspergillus are filamentous ubiquitous saprophytes that play a major role in lignocellulosic biomass recycling and also are considered as cell factories for the production of organic acids, pharmaceuticals, and industrially important enzymes. Analysis of extracellular secreted biomass degrading enzymes using complex lignocellulosic biomass as a substrate by solid-state fermentation could be a more practical approach to evaluate application of the enzymes for lignocellulosic biorefinery. This study isolated a fungal strain from compost, identified as Aspergillus fumigatus, and further analyzed it for lignocellulolytic enzymes at different temperatures using label free quantitative proteomics. The profile of secretome composition discovered cellulases, hemicellulases, lignin degrading proteins, peptidases and proteases, and transport and hypothetical proteins; while protein abundances and further their hierarchical clustering analysis revealed temperature dependent expression of these enzymes during solid-state fermentation of sawdust. The enzyme activities and protein abundances as determined by exponentially modified protein abundance index (emPAI) indicated the maximum activities at the range of 40-50 °C, demonstrating the thermophilic nature of the isolate A. fumigatus LF9. Characterization of the thermostability of secretome suggested the potential of the isolated fungal strain in the production of thermophilic biomass degrading enzymes for industrial application. PMID:23647126

  5. Highly Multiplexed and Reproducible Ion-Current-Based Strategy for Large-Scale Quantitative Proteomics and the Application to Protein Expression Dynamics Induced by Methylprednisolone in 60 Rats

    PubMed Central

    2015-01-01

    A proteome-level time-series study of drug effects (i.e., pharmacodynamics) is critical for understanding mechanisms of action and systems pharmacology, but is challenging, because of the requirement of a proteomics method for reliable quantification of many biological samples. Here, we describe a highly reproducible strategy, enabling a global, large-scale investigation of the expression dynamics of corticosteroid-regulated proteins in livers from adrenalectomized rats over 11 time points after drug dosing (0.5–66 h, N = 5/point). The analytical advances include (i) exhaustive tissue extraction with a Polytron/sonication procedure in a detergent cocktail buffer, and a cleanup/digestion procedure providing very consistent protein yields (relative standard deviation (RSD%) of 2.7%–6.4%) and peptide recoveries (4.1–9.0%) across the 60 animals; (ii) an ultrahigh-pressure nano-LC setup with substantially improved temperature stabilization, pump-noise suppression, and programmed interface cleaning, enabling excellent reproducibility for continuous analyses of numerous samples; (iii) separation on a 100-cm-long column (2-μm particles) with high reproducibility for days to enable both in-depth profiling and accurate peptide ion-current match; and (iv) well-controlled ion-current-based quantification. To obtain high-quality quantitative data necessary to describe the 11 time-points protein expression temporal profiles, strict criteria were used to define “quantifiable proteins”. A total of 323 drug-responsive proteins were revealed with confidence, and the time profiles of these proteins provided new insights into the diverse temporal changes of biological cascades associated with hepatic metabolism, response to hormone stimuli, gluconeogenesis, inflammatory responses, and protein translation processes. Most profile changes persisted well after the drug was eliminated. The developed strategy can also be broadly applied in preclinical and clinical research, where

  6. Effect of transverse current on Andreev bound state

    SciTech Connect

    Takahashi, Y.; Hashimoto, Y.; Yun, D. H.; Kim, S. W.; Nakamura, T.; Iye, Y.; Katsumoto, S.

    2013-12-04

    In a superconductor-normal-superconductor (SNS) structure, the effect of transverse current across the normal part on the transport through Andreev bound states (ABSs) has been examined. Here a ballistic InAs two-dimensional electron system (2DES) is used as the N-layer to form ABSs. At the same time the 2DES has strong spin-orbit interaction, hence there should emerge the spin-Hall effect associated with the transverse current. We have observed strong reduction of characteristic oscillation in the conductance versus bias voltage, which may be attributed to spin polarization due to the spin-Hall effect.

  7. Understanding the Current Dynamical States of Globular Clusters

    NASA Astrophysics Data System (ADS)

    Pooley, David

    2008-09-01

    We appear to be on the verge of a major paradigm shift in our understanding of the current dynamical states of Galactic globular clusters. Fregeau (2008) brought together two recent theoretical breakthroughs as well as an observational breakthrough made possible by Chandra -- that a globular cluster's X-ray source population scales with its dynamical encounter frequency -- to persuasively argue that we have misunderstood the dynamical states of Galactic globular clusters. The observational evidence hinges on Chandra results from clusters which are classified as "core collapsed," of which there are only a handful of observations. I propose a nearly complete census with Chandra of the rest of the "core collapsed" globular clusters.

  8. Steady-state current transfer and scattering theory.

    PubMed

    Ben-Moshe, Vered; Rai, Dhurba; Skourtis, Spiros S; Nitzan, Abraham

    2010-08-01

    The correspondence between the steady-state theory of current transfer and scattering theory in a system of coupled tight-binding models of one-dimensional wires is explored. For weak interwire coupling both calculations give nearly identical results, except at singular points associated with band edges. The effect of decoherence in each of these models is studied using a generalization of the Liouville-von Neuman equation suitable for steady-state situations. An example of a single impurity model is studied in detail, leading to a lattice model of scattering off target that affects both potential scattering and decoherence. For an impurity level lying inside the energy band, the transmission coefficient diminishes with increasing dephasing rate, while the opposite holds for impurity energy outside the band. The efficiency of current transfer in the coupled wire system decreases with increasing dephasing. PMID:20707524

  9. Proteomic Profiling of the Retinas in a Neonatal Rat Model of Oxygen-Induced Retinopathy with a Reproducible Ion-Current-Based MS1 Approach

    PubMed Central

    Shen, Xiaomeng; Li, Jun; Wang, Lianshui; Aranda, Jacob V.; Qu, Jun

    2015-01-01

    Investigation of the retina proteome during hypoxia-induced retinal neovascularization is valuable for understanding pathogenesis of retinopathy of prematurity (ROP). Here we employed a reproducible ion-current-based MS1 quantification approach (ICB) to explore the retinal proteomic changes in early stage of ROP in a rat model of oxygen-induced retinopathy (OIR). Retina proteins, which are rich in membrane proteins, were efficiently extracted by a detergent-cocktail and subjected to precipitation/on-pellet-digestion, followed by nano-LC-MS analysis on a 75-cm column with a 7-h gradient. The high reproducibility of sample preparation and chromatography separation enabled excellent peak alignment and contributed to the superior performance of ICB over parallel label-free approaches. In this study, sum-of-intensity with rejection was incorporated to determine the protein ratios. In total, 1325 unique protein groups were quantified from rat retinas (n = 4/group) with at least two distinct peptides at a protein FDR of 1%. Thirty-two significantly altered proteins were observed with confidence, and the elevated glial fibrillary acidic protein and decreased crystalline proteins in OIR retinas agree well with previous studies. Selected key alterations were further validated by Western blot analysis. Interestingly, Rab21/RhoA/ROCK2/moesin signaling pathway was found to be involved in retinal neovascularization of OIR. Moreover, highly elevated annexin A3, a potential angiogenic mediator, was observed in OIR retinas and may serve as a potential therapeutic target. In conclusion, reproducible ICB profiling enabled reliable discovery of many altered mediators and pathways in OIR retinas, thereby providing new insights into molecular mechanisms involved in pathogenesis of ROP. PMID:25780855

  10. Proteomic profiling of the retinas in a neonatal rat model of oxygen-induced retinopathy with a reproducible ion-current-based MS1 approach.

    PubMed

    Tu, Chengjian; Beharry, Kay D; Shen, Xiaomeng; Li, Jun; Wang, Lianshui; Aranda, Jacob V; Qu, Jun

    2015-05-01

    Investigation of the retina proteome during hypoxia-induced retinal neovascularization is valuable for understanding pathogenesis of retinopathy of prematurity (ROP). Here we employed a reproducible ion-current-based MS1 quantification approach (ICB) to explore the retinal proteomic changes in early stage of ROP in a rat model of oxygen-induced retinopathy (OIR). Retina proteins, which are rich in membrane proteins, were efficiently extracted by a detergent-cocktail and subjected to precipitation/on-pellet-digestion, followed by nano-LC-MS analysis on a 75-cm column with a 7-h gradient. The high reproducibility of sample preparation and chromatography separation enabled excellent peak alignment and contributed to the superior performance of ICB over parallel label-free approaches. In this study, sum-of-intensity with rejection was incorporated to determine the protein ratios. In total, 1325 unique protein groups were quantified from rat retinas (n = 4/group) with at least two distinct peptides at a protein FDR of 1%. Thirty-two significantly altered proteins were observed with confidence, and the elevated glial fibrillary acidic protein and decreased crystalline proteins in OIR retinas agree well with previous studies. Selected key alterations were further validated by Western blot analysis. Interestingly, Rab21/RhoA/ROCK2/moesin signaling pathway was found to be involved in retinal neovascularization of OIR. Moreover, highly elevated annexin A3, a potential angiogenic mediator, was observed in OIR retinas and may serve as a potential therapeutic target. In conclusion, reproducible ICB profiling enabled reliable discovery of many altered mediators and pathways in OIR retinas, thereby providing new insights into molecular mechanisms involved in pathogenesis of ROP. PMID:25780855

  11. Proteome Studies of Filamentous Fungi

    SciTech Connect

    Baker, Scott E.; Panisko, Ellen A.

    2011-04-20

    The continued fast pace of fungal genome sequence generation has enabled proteomic analysis of a wide breadth of organisms that span the breadth of the Kingdom Fungi. There is some phylogenetic bias to the current catalog of fungi with reasonable DNA sequence databases (genomic or EST) that could be analyzed at a global proteomic level. However, the rapid development of next generation sequencing platforms has lowered the cost of genome sequencing such that in the near future, having a genome sequence will no longer be a time or cost bottleneck for downstream proteomic (and transcriptomic) analyses. High throughput, non-gel based proteomics offers a snapshot of proteins present in a given sample at a single point in time. There are a number of different variations on the general method and technologies for identifying peptides in a given sample. We present a method that can serve as a “baseline” for proteomic studies of fungi.

  12. The Cysteine Proteome

    PubMed Central

    Go, Young-Mi; Chandler, Joshua D.; Jones, Dean P.

    2015-01-01

    The cysteine (Cys) proteome is a major component of the adaptive interface between the genome and the exposome. The thiol moiety of Cys undergoes a range of biologic modifications enabling biological switching of structure and reactivity. These biological modifications include sulfenylation and disulfide formation, formation of higher oxidation states, S-nitrosylation, persulfidation, metallation, and other modifications. Extensive knowledge about these systems and their compartmentalization now provides a foundation to develop advanced integrative models of Cys proteome regulation. In particular, detailed understanding of redox signaling pathways and sensing networks is becoming available to discriminate network structures. This research focuses attention on the need for atlases of Cys modifications to develop systems biology models. Such atlases will be especially useful for integrative studies linking the Cys proteome to imaging and other omics platforms, providing a basis for improved redox-based therapeutics. Thus, a framework is emerging to place the Cys proteome as a complement to the quantitative proteome in the omics continuum connecting the genome to the exposome. PMID:25843657

  13. The Current Status of Medical Marijuana in the United States

    PubMed Central

    2014-01-01

    Medical marijuana is currently a controversial issue in medicine. There are strong pro and con opinions but relatively little scientific data on which to base medical decisions. The unfortunate scheduling of marijuana in class I has limited research and only serves to fuel the controversy. This article will review the history of laws to regulate drugs in the United States in the 20th century to provide context for the current status of medical marijuana. It will include the rationale for opposing medical marijuana laws and the problem of the Schedule I inclusion of marijuana as well as other drugs. It will examine the problems associated with smoking raw marijuana and review other routes of administration. Finally, it examines the inadvisability of medicine's promotion of smoked marijuana. PMID:24765557

  14. Fueling Requirements for Steady State high butane current fraction discharges

    SciTech Connect

    R.Raman

    2003-10-08

    The CT injector originally used for injecting CTs into 1T toroidal field discharges in the TdeV tokamak was shipped PPPL from the Affiliated Customs Brokers storage facility in Montreal during November 2002. All components were transported safely, without damage, and are currently in storage at PPPL, waiting for further funding in order to begin advanced fueling experiments on NSTX. The components are currently insured through the University of Washington. Several technical presentations were made to investigate the feasibility of the CT injector installation on NSTX. These technical presentations, attached to this document, were: (1) Motivation for Compact Toroida Injection in NSTX; (2) Assessment of the Engineering Feasibility of Installing CTF-II on NSTX; (3) Assessment of the Cost for CT Installation on NSTX--A Peer Review; and (4) CT Fueling for NSTX FY 04-08 steady-state operation needs.

  15. Molecular Biologist's Guide to Proteomics

    PubMed Central

    Graves, Paul R.; Haystead, Timothy A. J.

    2002-01-01

    The emergence of proteomics, the large-scale analysis of proteins, has been inspired by the realization that the final product of a gene is inherently more complex and closer to function than the gene itself. Shortfalls in the ability of bioinformatics to predict both the existence and function of genes have also illustrated the need for protein analysis. Moreover, only through the study of proteins can posttranslational modifications be determined, which can profoundly affect protein function. Proteomics has been enabled by the accumulation of both DNA and protein sequence databases, improvements in mass spectrometry, and the development of computer algorithms for database searching. In this review, we describe why proteomics is important, how it is conducted, and how it can be applied to complement other existing technologies. We conclude that currently, the most practical application of proteomics is the analysis of target proteins as opposed to entire proteomes. This type of proteomics, referred to as functional proteomics, is always driven by a specific biological question. In this way, protein identification and characterization has a meaningful outcome. We discuss some of the advantages of a functional proteomics approach and provide examples of how different methodologies can be utilized to address a wide variety of biological problems. PMID:11875127

  16. Persistent Probability Currents in Non-equilibrium Steady States

    NASA Astrophysics Data System (ADS)

    Zia, Royce; Mellor, Andrew; Mobilia, Mauro; Fox-Kemper, Baylor; Weiss, Jeffrey

    For many interesting phenomena in nature, from all life forms to the global climate, the fundamental hypothesis of equilibrium statistical mechanics does not apply. Instead, they are perhaps better characterized by non-equilibrium steady states, evolving with dynamical rules which violate detailed balance. In particular, such dynamics leads to the existence of non-trivial, persistent probability currents - a principal characteristic of non-equilibrium steady states. In turn, they give rise to the notion of 'probability angular momentum'. Observable manifestations of such abstract concepts will be illustrated in two distinct contexts: a heterogeneous nonlinear voter model and our ocean heat content. Supported in part by grants from the Bloom Agency (Leeds, UK) and the US National Science Foundation: OCE-1245944. AM acknowledges the support of EPSRC Industrial CASE Studentship, Grant No. EP/L50550X/1.

  17. Animal Models of Psychosis: Current State and Future Directions

    PubMed Central

    Forrest, Alexandra D.; Coto, Carlos A.; Siegel, Steven J.

    2014-01-01

    Psychosis is an abnormal mental state characterized by disorganization, delusions and hallucinations. Animal models have become an increasingly important research tool in the effort to understand both the underlying pathophysiology and treatment of psychosis. There are multiple animal models for psychosis, with each formed by the coupling of a manipulation and a measurement. In this manuscript we do not address the diseases of which psychosis is a prominent comorbidity. Instead, we summarize the current state of affairs and future directions for animal models of psychosis. To accomplish this, our manuscript will first discuss relevant behavioral and electrophysiological measurements. We then provide an overview of the different manipulations that are combined with these measurements to produce animal models. The strengths and limitations of each model will be addressed in order to evaluate its cross-species comparability. PMID:25215267

  18. Geographical Information Systems and Health: Current State and Future Directions

    PubMed Central

    2012-01-01

    This paper provides an introduction to Geographical Information Systems (GIS) and how they can be used. It reviews the current state of GIS use in health care before identifying the barriers to more pervasive use of GIS in health. Finally, it makes recommendations for the direction of health GIS research over the next decade and concludes with a call to action to health informatics researchers to stop ignoring a tool and methodology that has such immense potential for improving the health of our communities. PMID:22844644

  19. Assessment of voice quality: Current state-of-the-art.

    PubMed

    Barsties, Ben; De Bodt, Marc

    2015-06-01

    Voice quality is not clearly defined but it can be concluded that it is a multidimensional perceived construct. Therefore, there are broadly two approaches to measure voice quality: (1) subjective measurements to score a client's voice that reflects his or her judgment of the voice and (2) objective measurements by applying specific algorithm to quantify certain aspects of a correlate of vocal production. This paper proposes a collection and discusses a number of critical issues of the current state-of-the-art in voice quality assessments of auditory-perceptual judgment, objective-acoustic analysis and aerodynamic measurements in clinical practice and research that maybe helpful for clinicians and researchers. PMID:25440411

  20. Skewness of steady-state current fluctuations in nonequilibrium systems

    NASA Astrophysics Data System (ADS)

    Belousov, Roman; Cohen, E. G. D.; Wong, Chun-Shang; Goree, John A.; Feng, Yan

    2016-04-01

    A skewness of the probability for instantaneous current fluctuations, in a nonequilibrium steady state, is observed experimentally in a dusty plasma. This skewness is attributed to the spatial asymmetry, which is imminent to the nonequilibrium systems due to the external hydrodynamic gradient. Using the modern framework of the large deviation theory, we extend the Onsager-Machlup ansatz for equilibrium fluctuations to systems with a preferred spatial direction, and provide a modulated Gaussian probability distribution, which is tested by simulations. This probability distribution is also of potential interest for other statistical disciplines. Connections with the principles of statistical mechanics, due to Boltzmann and Gibbs, are discussed as well.

  1. A proteomic approach reveals integrin activation state-dependent control of microtubule cortical targeting.

    PubMed

    Byron, Adam; Askari, Janet A; Humphries, Jonathan D; Jacquemet, Guillaume; Koper, Ewa J; Warwood, Stacey; Choi, Colin K; Stroud, Matthew J; Chen, Christopher S; Knight, David; Humphries, Martin J

    2015-01-01

    Integrin activation, which is regulated by allosteric changes in receptor conformation, enables cellular responses to the chemical, mechanical and topological features of the extracellular microenvironment. A global view of how activation state converts the molecular composition of the region proximal to integrins into functional readouts is, however, lacking. Here, using conformation-specific monoclonal antibodies, we report the isolation of integrin activation state-dependent complexes and their characterization by mass spectrometry. Quantitative comparisons, integrating network, clustering, pathway and image analyses, define multiple functional protein modules enriched in a conformation-specific manner. Notably, active integrin complexes are specifically enriched for proteins associated with microtubule-based functions. Visualization of microtubules on micropatterned surfaces and live cell imaging demonstrate that active integrins establish an environment that stabilizes microtubules at the cell periphery. These data provide a resource for the interrogation of the global molecular connections that link integrin activation to adhesion signalling. PMID:25609142

  2. A proteomic approach reveals integrin activation state-dependent control of microtubule cortical targeting

    PubMed Central

    Byron, Adam; Askari, Janet A.; Humphries, Jonathan D.; Jacquemet, Guillaume; Koper, Ewa J.; Warwood, Stacey; Choi, Colin K.; Stroud, Matthew J.; Chen, Christopher S.; Knight, David; Humphries, Martin J.

    2015-01-01

    Integrin activation, which is regulated by allosteric changes in receptor conformation, enables cellular responses to the chemical, mechanical and topological features of the extracellular microenvironment. A global view of how activation state converts the molecular composition of the region proximal to integrins into functional readouts is, however, lacking. Here, using conformation-specific monoclonal antibodies, we report the isolation of integrin activation state-dependent complexes and their characterization by mass spectrometry. Quantitative comparisons, integrating network, clustering, pathway and image analyses, define multiple functional protein modules enriched in a conformation-specific manner. Notably, active integrin complexes are specifically enriched for proteins associated with microtubule-based functions. Visualization of microtubules on micropatterned surfaces and live cell imaging demonstrate that active integrins establish an environment that stabilizes microtubules at the cell periphery. These data provide a resource for the interrogation of the global molecular connections that link integrin activation to adhesion signalling. PMID:25609142

  3. Ultra-Fast Sample Preparation for High-Throughput Proteomics

    SciTech Connect

    Lopez-Ferrer, Daniel; Hixson, Kim K.; Belov, Mikhail E.; Smith, Richard D.

    2011-06-21

    Sample preparation oftentimes can be the Achilles Heel of any analytical process and in the field of proteomics, preparing samples for mass spectrometric analysis is no exception. Current goals, concerning proteomic sample preparation on a large scale, include efforts toward improving reproducibility, reducing the time of processing and ultimately the automation of the entire workflow. This chapter reviews an array of recent approaches applied to bottom-up proteomics sample preparation to reduce the processing time down from hours to minutes. The current state-of-the-art in the field uses different energy inputs like microwave, ultrasound or pressure to perform the four basic steps in sample preparation: protein extraction, denaturation, reduction and alkylation, and digestion. No single energy input for enhancement of proteome sample preparation has become the universal gold standard. Instead, a combination of different energy inputs tend to produce the best results. This chapter further describes the future trends in the field such as the hyphenation of sample preparation with downstream detection and analysis systems. Finally, a detailed protocol describing the combined use of both pressure cycling technology and ultrasonic energy inputs to hasten proteomic sample preparation is presented.

  4. Compact solid-state neutral particle analyzer in current mode.

    PubMed

    Zhu, Y B; Bortolon, A; Heidbrink, W W; Celle, S L; Roquemore, A L

    2012-10-01

    Solid state neutral particle analyzer (ssNPA) arrays are operated in current mode on the DIII-D tokamak and the National Spherical Torus Experiment (NSTX). Compared with conventional pulse-counting NPAs, current-mode operation sacrifices energy resolution to obtain economical, high-bandwidth, pitch-angle resolved measurements. With the success from a new three-channel near-vertical-view current mode ssNPA on DIII-D, the apertures on an existing array on NSTX were expanded to increase the particle influx. The sightlines of both arrays intersect heating beams, enabling both active and passive charge exchange measurements. The spatial resolution at beam intersection is typically 5 cm on both devices. Directly deposited ultra-thin foils on the detector surface block stray photons below the energy of 1 keV and also set low energy threshold about 25 keV for deuterium particle detection. Oscillations in neutral flux produced by high frequency magnetohydrodynamics (MHD) instabilities are readily detected. PMID:23126831

  5. Proteomics Links the Redox State to Calcium Signaling During Bleaching of the Scleractinian Coral Acropora microphthalma on Exposure to High Solar Irradiance and Thermal Stress

    PubMed Central

    Weston, Andrew J.; Dunlap, Walter C.; Beltran, Victor H.; Starcevic, Antonio; Hranueli, Daslav; Ward, Malcolm; Long, Paul F.

    2015-01-01

    Shipboard experiments were each performed over a 2 day period to examine the proteomic response of the symbiotic coral Acropora microphthalma exposed to acute conditions of high temperature/low light or high light/low temperature stress. During these treatments, corals had noticeably bleached. The photosynthetic performance of residual algal endosymbionts was severely impaired but showed signs of recovery in both treatments by the end of the second day. Changes in the coral proteome were determined daily and, using recently available annotated genome sequences, the individual contributions of the coral host and algal endosymbionts could be extracted from these data. Quantitative changes in proteins relevant to redox state and calcium metabolism are presented. Notably, expression of common antioxidant proteins was not detected from the coral host but present in the algal endosymbiont proteome. Possible roles for elevated carbonic anhydrase in the coral host are considered: to restore intracellular pH diminished by loss of photosynthetic activity, to indirectly limit intracellular calcium influx linked with enhanced calmodulin expression to impede late-stage symbiont exocytosis, or to enhance inorganic carbon transport to improve the photosynthetic performance of algal symbionts that remain in hospite. Protein effectors of calcium-dependent exocytosis were present in both symbiotic partners. No caspase-family proteins associated with host cell apoptosis, with exception of the autophagy chaperone HSP70, were detected, suggesting that algal loss and photosynthetic dysfunction under these experimental conditions were not due to host-mediated phytosymbiont destruction. Instead, bleaching occurred by symbiont exocytosis and loss of light-harvesting pigments of algae that remain in hospite. These proteomic data are, therefore, consistent with our premise that coral endosymbionts can mediate their own retention or departure from the coral host, which may manifest as

  6. Proteomics links the redox state to calcium signaling during bleaching of the scleractinian coral Acropora microphthalma on exposure to high solar irradiance and thermal stress.

    PubMed

    Weston, Andrew J; Dunlap, Walter C; Beltran, Victor H; Starcevic, Antonio; Hranueli, Daslav; Ward, Malcolm; Long, Paul F

    2015-03-01

    Shipboard experiments were each performed over a 2 day period to examine the proteomic response of the symbiotic coral Acropora microphthalma exposed to acute conditions of high temperature/low light or high light/low temperature stress. During these treatments, corals had noticeably bleached. The photosynthetic performance of residual algal endosymbionts was severely impaired but showed signs of recovery in both treatments by the end of the second day. Changes in the coral proteome were determined daily and, using recently available annotated genome sequences, the individual contributions of the coral host and algal endosymbionts could be extracted from these data. Quantitative changes in proteins relevant to redox state and calcium metabolism are presented. Notably, expression of common antioxidant proteins was not detected from the coral host but present in the algal endosymbiont proteome. Possible roles for elevated carbonic anhydrase in the coral host are considered: to restore intracellular pH diminished by loss of photosynthetic activity, to indirectly limit intracellular calcium influx linked with enhanced calmodulin expression to impede late-stage symbiont exocytosis, or to enhance inorganic carbon transport to improve the photosynthetic performance of algal symbionts that remain in hospite. Protein effectors of calcium-dependent exocytosis were present in both symbiotic partners. No caspase-family proteins associated with host cell apoptosis, with exception of the autophagy chaperone HSP70, were detected, suggesting that algal loss and photosynthetic dysfunction under these experimental conditions were not due to host-mediated phytosymbiont destruction. Instead, bleaching occurred by symbiont exocytosis and loss of light-harvesting pigments of algae that remain in hospite. These proteomic data are, therefore, consistent with our premise that coral endosymbionts can mediate their own retention or departure from the coral host, which may manifest as

  7. Transcriptomic and proteomic analyses of Desulfovibrio vulgaris biofilms: Carbon and energy flow contribute to the distinct biofilm growth state

    PubMed Central

    2012-01-01

    Background Desulfovibrio vulgaris Hildenborough is a sulfate-reducing bacterium (SRB) that is intensively studied in the context of metal corrosion and heavy-metal bioremediation, and SRB populations are commonly observed in pipe and subsurface environments as surface-associated populations. In order to elucidate physiological changes associated with biofilm growth at both the transcript and protein level, transcriptomic and proteomic analyses were done on mature biofilm cells and compared to both batch and reactor planktonic populations. The biofilms were cultivated with lactate and sulfate in a continuously fed biofilm reactor, and compared to both batch and reactor planktonic populations. Results The functional genomic analysis demonstrated that biofilm cells were different compared to planktonic cells, and the majority of altered abundances for genes and proteins were annotated as hypothetical (unknown function), energy conservation, amino acid metabolism, and signal transduction. Genes and proteins that showed similar trends in detected levels were particularly involved in energy conservation such as increases in an annotated ech hydrogenase, formate dehydrogenase, pyruvate:ferredoxin oxidoreductase, and rnf oxidoreductase, and the biofilm cells had elevated formate dehydrogenase activity. Several other hydrogenases and formate dehydrogenases also showed an increased protein level, while decreased transcript and protein levels were observed for putative coo hydrogenase as well as a lactate permease and hyp hydrogenases for biofilm cells. Genes annotated for amino acid synthesis and nitrogen utilization were also predominant changers within the biofilm state. Ribosomal transcripts and proteins were notably decreased within the biofilm cells compared to exponential-phase cells but were not as low as levels observed in planktonic, stationary-phase cells. Several putative, extracellular proteins (DVU1012, 1545) were also detected in the extracellular fraction from

  8. Immunocapture strategies in translational proteomics

    PubMed Central

    Fredolini, Claudia; Byström, Sanna; Pin, Elisa; Edfors, Fredrik; Tamburro, Davide; Iglesias, Maria Jesus; Häggmark, Anna; Hong, Mun-Gwan; Uhlen, Mathias; Nilsson, Peter; Schwenk, Jochen M

    2016-01-01

    Aiming at clinical studies of human diseases, antibody-assisted assays have been applied to biomarker discovery and toward a streamlined translation from patient profiling to assays supporting personalized treatments. In recent years, integrated strategies to couple and combine antibodies with mass spectrometry-based proteomic efforts have emerged, allowing for novel possibilities in basic and clinical research. Described in this review are some of the field’s current and emerging immunocapture approaches from an affinity proteomics perspective. Discussed are some of their advantages, pitfalls and opportunities for the next phase in clinical and translational proteomics. PMID:26558424

  9. The potential versus current state of water splitting with hematite.

    PubMed

    Zandi, Omid; Hamann, Thomas W

    2015-09-21

    This review describes the potential of hematite as a photoanode material for photoelectrochemical (PEC) water splitting. The current understanding of key loss-mechanisms of hematite are introduced and correlated to performance enhancement strategies. The significant voltage loss associated with overcoming the competitive water oxidation and surface state recombination has recently been surmounted through a combination of high temperature annealing and surface modification with water oxidation catalysts. Substantial efforts have been made at nanostructuring electrodes to increase the charge separation efficiency without sacrificing light absorption. Even in optimized nanostructured electrodes, however, charge separation continues to be the primary barrier to achieving efficient water splitting with hematite. Specifically, significant depletion region recombination results in voltage dependant photocurrent which constrains the fill factor. Thus, future directions to enhance the efficiency of hematite electrodes are discussed with an emphasis on circumventing depletion region recombination. PMID:26267040

  10. The Current State of Silicone-Based Dielectric Elastomer Transducers.

    PubMed

    Madsen, Frederikke B; Daugaard, Anders E; Hvilsted, Søren; Skov, Anne L

    2016-03-01

    Silicone elastomers are promising materials for dielectric elastomer transducers (DETs) due to their superior properties such as high efficiency, reliability and fast response times. DETs consist of thin elastomer films sandwiched between compliant electrodes, and they constitute an interesting class of transducer due to their inherent lightweight and potentially large strains. For the field to progress towards industrial implementation, a leap in material development is required, specifically targeting longer lifetime and higher energy densities to provide more efficient transduction at lower driving voltages. In this review, the current state of silicone elastomers for DETs is summarised and critically discussed, including commercial elastomers, composites, polymer blends, grafted elastomers and complex network structures. For future developments in the field it is essential that all aspects of the elastomer are taken into account, namely dielectric losses, lifetime and the very often ignored polymer network integrity and stability. PMID:26773231

  11. Sweetened beverages and health: current state of scientific understandings.

    PubMed

    Rippe, James M; Saltzman, Edward

    2013-01-01

    This article summarizes the presentations from the "Sweetened Beverages and Health: Current State of Scientific Understandings" symposium held at the ASN Annual Meeting in Boston, MA on April 23, 2013. The metabolic and health effects of sugar-sweetened beverages were discussed from a variety of points of view by 5 different presenters. Dr. David Allison drew a distinction between conjecture and proof related to sweetened beverages and obesity. Dr. Richard Mattes discussed differences between solid and liquid calories. Dr. Miguel Alonso-Alonso reviewed potential contributions of functional neuroimaging, particularly as they relate to whether sugar is potentially "addictive." Dr. Kimber Stanhope discussed work related to experiments comparing fructose to glucose. Dr. James Rippe presented evidence from randomized controlled trials from his research organization showing no differences among high-fructose corn syrup, sucrose, glucose, or fructose at normal human consumption amounts. PMID:24038246

  12. Single-cell genome sequencing: current state of the science.

    PubMed

    Gawad, Charles; Koh, Winston; Quake, Stephen R

    2016-03-01

    The field of single-cell genomics is advancing rapidly and is generating many new insights into complex biological systems, ranging from the diversity of microbial ecosystems to the genomics of human cancer. In this Review, we provide an overview of the current state of the field of single-cell genome sequencing. First, we focus on the technical challenges of making measurements that start from a single molecule of DNA, and then explore how some of these recent methodological advancements have enabled the discovery of unexpected new biology. Areas highlighted include the application of single-cell genomics to interrogate microbial dark matter and to evaluate the pathogenic roles of genetic mosaicism in multicellular organisms, with a focus on cancer. We then attempt to predict advances we expect to see in the next few years. PMID:26806412

  13. Nanoscale Proteomics

    SciTech Connect

    Shen, Yufeng; Tolic, Nikola; Masselon, Christophe D.; Pasa-Tolic, Liljiana; Camp, David G.; Anderson, Gordon A.; Smith, Richard D.; Lipton, Mary S.

    2004-02-01

    This paper describes efforts to develop a liquid chromatography (LC)/mass spectrometry (MS) technology for ultra-sensitive proteomics studies, i.e. nanoscale proteomics. The approach combines high-efficiency nano-scale LC with advanced MS, including high sensitivity and high resolution Fourier transform ion cyclotron resonance (FTICR) MS, to perform both single-stage MS and tandem MS (MS/MS) proteomic analyses. The technology developed enables large-scale protein identification from nanogram size proteomic samples and characterization of more abundant proteins from sub-picogram size complex samples. Protein identification in such studies using MS is feasible from <75 zeptomole of a protein, and the average proteome measurement throughput is >200 proteins/h and ~3 h/sample. Higher throughput (>1000 proteins/h) and more sensitive detection limits can be obtained using a “accurate mass and time” tag approach developed at our laboratory. These capabilities lay the foundation for studies from single or limited numbers of cells.

  14. Recommendations for biomarker identification and qualification in clinical proteomics.

    PubMed

    Mischak, Harald; Allmaier, Günter; Apweiler, Rolf; Attwood, Teresa; Baumann, Marc; Benigni, Ariela; Bennett, Samuel E; Bischoff, Rainer; Bongcam-Rudloff, Erik; Capasso, Giovambattista; Coon, Joshua J; D'Haese, Patrick; Dominiczak, Anna F; Dakna, Mohammed; Dihazi, Hassan; Ehrich, Jochen H; Fernandez-Llama, Patricia; Fliser, Danilo; Frokiaer, Jorgen; Garin, Jerome; Girolami, Mark; Hancock, William S; Haubitz, Marion; Hochstrasser, Denis; Holman, Rury R; Ioannidis, John P A; Jankowski, Joachim; Julian, Bruce A; Klein, Jon B; Kolch, Walter; Luider, Theo; Massy, Ziad; Mattes, William B; Molina, Franck; Monsarrat, Bernard; Novak, Jan; Peter, Karlheinz; Rossing, Peter; Sánchez-Carbayo, Marta; Schanstra, Joost P; Semmes, O John; Spasovski, Goce; Theodorescu, Dan; Thongboonkerd, Visith; Vanholder, Raymond; Veenstra, Timothy D; Weissinger, Eva; Yamamoto, Tadashi; Vlahou, Antonia

    2010-08-25

    Clinical proteomics has yielded some early positive results-the identification of potential disease biomarkers-indicating the promise for this analytical approach to improve the current state of the art in clinical practice. However, the inability to verify some candidate molecules in subsequent studies has led to skepticism among many clinicians and regulatory bodies, and it has become evident that commonly encountered shortcomings in fundamental aspects of experimental design mainly during biomarker discovery must be addressed in order to provide robust data. In this Perspective, we assert that successful studies generally use suitable statistical approaches for biomarker definition and confirm results in independent test sets; in addition, we describe a brief set of practical and feasible recommendations that we have developed for investigators to properly identify and qualify proteomic biomarkers, which could also be used as reporting requirements. Such recommendations should help put proteomic biomarker discovery on the solid ground needed for turning the old promise into a new reality. PMID:20739680

  15. ["Good dying"--definition and current state of research].

    PubMed

    Hutter, Nico; Stößel, Ulrich; Meffert, Cornelia; Körner, Mirjam; Bozzaro, Claudia; Becker, Gerhild; Baumeister, Harald

    2015-08-01

    The advances of modern medicine did not only result in prolongation of life expectancy, but also led to a shift from dying at home to dying in public institutions. In western countries most people die at advanced age in medical facilities. Hence, the question regarding the conditions, which should be provided by society and especially medicine, to allow terminally ill people to experience "good dying" is substantial. For this purpose, an examination of patients', family members' and health care providers' understanding of the term " good dying" is required. The present paper aims at shedding light on the term "good dying" and to summarize the current state of research. Therefore, the attributes of "good dying" will be described from the perspectives of patients, family members and health care providers, which are discussed and examined in current medical-sociological research. These attributes can be illustrated on three dimensions: Quality of life at the end of life (e. g. pain relief, mental well-being), quality of dying (e. g. avoiding prolonged dying, autonomy, presence of relatives) and quality of health care at the end of life (e. g. patient-oriented health care, positive communication between health care providers and patients, availability of guidelines). Although the attributes of "good dying" are described in detail in the existing literature, further studies have to clarify the relevance and impact of these attributes as predictors of "good dying". PMID:26306020

  16. Proton Therapy Expansion Under Current United States Reimbursement Models

    SciTech Connect

    Kerstiens, John; Johnstone, Peter A.S.

    2014-06-01

    Purpose: To determine whether all the existing and planned proton beam therapy (PBT) centers in the United States can survive on a local patient mix that is dictated by insurers, not by number of patients. Methods and Materials: We determined current and projected cancer rates for 10 major US metropolitan areas. Using published utilization rates, we calculated patient percentages who are candidates for PBT. Then, on the basis of current published insurer coverage policies, we applied our experience of what would be covered to determine the net number of patients for whom reimbursement is expected. Having determined the net number of covered patients, we applied our average beam delivery times to determine the total number of minutes needed to treat that patient over the course of their treatment. We then calculated our expected annual patient capacity per treatment room to determine the appropriate number of treatment rooms for the area. Results: The population of patients who will be both PBT candidates and will have treatments reimbursed by insurance is significantly smaller than the population who should receive PBT. Coverage decisions made by insurers reduce the number of PBT rooms that are economically viable. Conclusions: The expansion of PBT centers in the US is not sustainable under the current reimbursement model. Viability of new centers will be limited to those operating in larger regional metropolitan areas, and few metropolitan areas in the US can support multiple centers. In general, 1-room centers require captive (non–PBT-served) populations of approximately 1,000,000 lives to be economically viable, and a large center will require a population of >4,000,000 lives. In areas with smaller populations or where or a PBT center already exists, new centers require subsidy.

  17. Beyond astronaut's capabilities: The current state of the art.

    PubMed

    Gemignani, Jessica; Gheysens, Tom; Summerer, Leopold

    2015-08-01

    Space agencies have developed extensive expertise with sustaining human presence in low earth orbits and microgravity. Prolonged human presence in space beyond EarthâĂŹs orbit presents additional, some still unsolved issues. These are linked to the distance to Earth (impossibility of effective tele-operation, psychological effects linked to remoteness from Earth, required autonomy, the handling of emergencies, long mission durations), and to the environments beyond the Earth magnetosphere (radiation levels, local environments including atmospheres, dust, gravity, day-night cycles). These issues have impacts on the spacecraft design, the mission operations, astronaut selection and preparation and required supporting/ enabling technologies. This paper builds upon previous work by Rossini et al. , in critically reviewing and updating the current state of scientific research on enhancing astronaut's capabilities to face some of these challenges. In particular, it discusses the pertinence and feasibility of two approaches aiming at enhancing the chances of success of human missions: induced hibernation state and brain-machine interfaces. PMID:26737075

  18. A Sydney proteome story.

    PubMed

    Williams, Keith L; Gooley, Andrew A; Wilkins, Marc R; Packer, Nicolle H

    2014-07-31

    This is the story of the experience of a multidisciplinary group at Macquarie University in Sydney as we participated in, and impacted upon, major currents that washed through protein science as the field of Proteomics emerged. The large scale analysis of proteins became possible. This is not a history of the field. Instead we have tried to encapsulate the stimulating personal ride we had transiting from conventional academe, to a Major National Research Facility, to the formation of Proteomics company Proteome Systems Ltd. There were lots of blind alleys, wrong directions, but we also got some things right and our efforts, along with those of many other groups around the world, did change the face of protein science. While the transformation is by no means yet complete, protein science is very different from the field in the 1990s. This article is part of a Special Issue entitled: 20years of Proteomics in memory of Viatliano Pallini. Guest Editors: Luca Bini, Juan J. Calvete, Natacha Turck, Denis Hochstrasser and Jean-Charles Sanchez. PMID:24735915

  19. Current state of hereditary angioedema management: A patient survey

    PubMed Central

    Busse, Paula; Christiansen, Sandra C.; Li, Henry; Lumry, William; Davis-Lorton, Mark; Bernstein, Jonathan A.; Frank, Michael; Castaldo, Anthony; Long, Janet F.; Zuraw, Bruce L.; Riedl, Marc

    2015-01-01

    Hereditary angioedema (HAE) is a chronic disease with a high burden of disease that is poorly understood and often misdiagnosed. Availability of treatments, including C1 esterase inhibitor (C1INH) replacement, ecallantide, and icatibant, marks a significant advance for HAE patients. We aimed to better understand the current state of HAE care, from a patient perspective, after the introduction of several novel therapies. One session of the United States Hereditary Angioedema Association 2013 patient summit was devoted to data collection for this study. Patients attending the summit were self-selected, and HAE diagnosis was self-reported. Survey questions assessed patient characteristics, burden of disease, and treatment. Participant responses were captured using an audience response system. We surveyed 149 (80%) type I and II HAE (HAE-C1INH) and 37 (20%) HAE with normal C1INH (HAE-nlC1INH) patients. HAE-C1INH (72%) and HAE-nlCINH patients (76%) equally reported that HAE had a significant impact on quality of life (QOL). A third of HAE-C1INH patients were diagnosed within one year of their first HAE attack, but another third reported a delay of more than 10 years. Most HAE-C1INH (88%) and HAE-nlC1INH (76%) patients had on-demand treatment available. HAE-C1INH patients frequently had an individual treatment plan (76%) compared with 50% of HAE-nlC1INH patients. Most HAE-C1INH patients went to the emergency department (ED) or were hospitalized less than once every six months (80%). Our findings show that HAE management is improving with good access to on-demand and prophylactic treatment options. However, HAE patients still have a significant burden of disease and continued research and educational efforts are needed. PMID:25976438

  20. Plant proteomics methods and protocols.

    PubMed

    Jorrin-Novo, Jesus V

    2014-01-01

    In this first, introductory chapter, it is intended to summarize from a methodological point of view the state of the art in plant proteomics, focusing on mass spectrometry-based strategies. Thus, this chapter is mainly directed at beginners or at those trying to get into the field, rather than at those with real experience or a long trajectory in plant proteomics research. The different alternative workflows, methods, techniques, and protocols from the experimental design to the data analysis will be briefly commented, with cross references to previous monographs and reviews, as well as to the rest of the book chapters. The difficulty of working with proteins, together with the power, limitations, and challenges of the approach will also be briefly discussed.Proteins, as molecular entities, and the cell proteome, as a whole, are much more complex than what we thought in the past and can be studied in a single experiment. Because of that, fractionation and complementary strategies are required for its study. The MS analysis of complex samples may result in up to 100,000-peptide spectra that cannot be easily analyzed with standard procedures. Therefore, proteomics, more than other -omics, needs a dry lab, time, and an effort in data mining.As main conclusion, it can be stated that proteomics is in its beginnings. It is starting to make important contributions to a proper gene annotation, identification, and characterization of gene products or protein species and to the knowledge of living organisms, having also an enormous application potential to translational research. However, and despite its great potential, and as in any other experimental approach, it is far from being a Pandora's Box. In the case of plant research, the full potential of proteomics is quite far from being totally exploited, and second-, third-, and fourth-generation proteomics techniques are still of very limited use. Most of the plant proteomics papers so far published belong to the

  1. Novel Molecular Insights into Classical and Alternative Activation States of Microglia as Revealed by Stable Isotope Labeling by Amino Acids in Cell Culture (SILAC)-based Proteomics*

    PubMed Central

    Bell-Temin, Harris; Culver-Cochran, Ashley E.; Chaput, Dale; Carlson, Christina M.; Kuehl, Melanie; Burkhardt, Brant R.; Bickford, Paula C.; Liu, Bin; Stevens, Stanley M.

    2015-01-01

    Microglia, the resident immune cells of the brain, have been shown to display a complex spectrum of roles that span from neurotrophic to neurotoxic depending on their activation status. Microglia can be classified into four stages of activation, M1, which most closely matches the classical (pro-inflammatory) activation stage, and the alternative activation stages M2a, M2b, and M2c. The alternative activation stages have not yet been comprehensively analyzed through unbiased, global-scale protein expression profiling. In this study, BV2 mouse immortalized microglial cells were stimulated with agonists specific for each of the four stages and total protein expression for 4644 protein groups was quantified using SILAC-based proteomic analysis. After validating induction of the various stages through a targeted cytokine assay and Western blotting of activation states, the data revealed novel insights into the similarities and differences between the various states. The data identify several protein groups whose expression in the anti-inflammatory, pro-healing activation states are altered presumably to curtail inflammatory activation through differential protein expression, in the M2a state including CD74, LYN, SQST1, TLR2, and CD14. The differential expression of these proteins promotes healing, limits phagocytosis, and limits activation of reactive nitrogen species through toll-like receptor cascades. The M2c state appears to center around the down-regulation of a key member in the formation of actin-rich phagosomes, SLP-76. In addition, the proteomic data identified a novel activation marker, DAB2, which is involved in clathrin-mediated endocytosis and is significantly different between M2a and either M1 or M2b states. Western blot analysis of mouse primary microglia stimulated with the various agonists of the classical and alternative activation states revealed a similar trend of DAB2 expression compared with BV2 cells. PMID:26424600

  2. Novel Molecular Insights into Classical and Alternative Activation States of Microglia as Revealed by Stable Isotope Labeling by Amino Acids in Cell Culture (SILAC)-based Proteomics.

    PubMed

    Bell-Temin, Harris; Culver-Cochran, Ashley E; Chaput, Dale; Carlson, Christina M; Kuehl, Melanie; Burkhardt, Brant R; Bickford, Paula C; Liu, Bin; Stevens, Stanley M

    2015-12-01

    Microglia, the resident immune cells of the brain, have been shown to display a complex spectrum of roles that span from neurotrophic to neurotoxic depending on their activation status. Microglia can be classified into four stages of activation, M1, which most closely matches the classical (pro-inflammatory) activation stage, and the alternative activation stages M2a, M2b, and M2c. The alternative activation stages have not yet been comprehensively analyzed through unbiased, global-scale protein expression profiling. In this study, BV2 mouse immortalized microglial cells were stimulated with agonists specific for each of the four stages and total protein expression for 4644 protein groups was quantified using SILAC-based proteomic analysis. After validating induction of the various stages through a targeted cytokine assay and Western blotting of activation states, the data revealed novel insights into the similarities and differences between the various states. The data identify several protein groups whose expression in the anti-inflammatory, pro-healing activation states are altered presumably to curtail inflammatory activation through differential protein expression, in the M2a state including CD74, LYN, SQST1, TLR2, and CD14. The differential expression of these proteins promotes healing, limits phagocytosis, and limits activation of reactive nitrogen species through toll-like receptor cascades. The M2c state appears to center around the down-regulation of a key member in the formation of actin-rich phagosomes, SLP-76. In addition, the proteomic data identified a novel activation marker, DAB2, which is involved in clathrin-mediated endocytosis and is significantly different between M2a and either M1 or M2b states. Western blot analysis of mouse primary microglia stimulated with the various agonists of the classical and alternative activation states revealed a similar trend of DAB2 expression compared with BV2 cells. PMID:26424600

  3. Functional proteomics of barley and barley chloroplasts – strategies, methods and perspectives

    PubMed Central

    Petersen, Jørgen; Rogowska-Wrzesinska, Adelina; Jensen, Ole N.

    2013-01-01

    Barley (Hordeum vulgare) is an important cereal grain that is used in a range of products for animal and human consumption. Crop yield and seed quality has been optimized during decades by plant breeding programs supported by biotechnology and molecular biology techniques. The recently completed whole-genome sequencing of barley revealed approximately 26,100 open reading frames, which provides a foundation for detailed molecular studies of barley by functional genomics and proteomics approaches. Such studies will provide further insights into the mechanisms of, for example, drought and stress tolerance, micronutrient utilization, and photosynthesis in barley. In the present review we present the current state of proteomics research for investigations of barley chloroplasts, i.e., the organelle that contain the photosynthetic apparatus in the plant. We describe several different proteomics strategies and discuss their applications in characterization of the barley chloroplast as well as future perspectives for functional proteomics in barley research. PMID:23515231

  4. Sunscreens in the United States: current status and future outlook.

    PubMed

    Jou, Paul C; Tomecki, Kenneth J

    2014-01-01

    Incidence rates of nonmelanoma skin cancer and melanoma has been on the rise in the United States for the past 20 years. UV radiation (UVR) exposure remains the most preventable environmental risk factor for these cancers. Aside from sun avoidance, sunscreens remain our best protection. UVR directly damages DNA and cause indirect cellular damage through the creation of reactive oxygen species, the sum of which leads to cutaneous immunosuppression and a tumorigenic milieu. The current generation of sunscreens protect from UVR through two main mechanisms: absorption and deflection. In the US, new Food and Drug Association rules require sunscreen manufacturers to evaluate their products not only on sun protection factor but also on broad spectrum UVA protection by the end of 2013. New labeling requirements will also be instituted. The American Academy of Dermatology and the American Academy of Pediatrics have provided specific recommendations for proper sun protection and sunscreen usage. Plant polyphenols such as those isolated from green tea, pomegranate, and grape seed remain an interesting avenue of research as additives to sunscreens or stand-alone products that appear to modulate the immunosuppressive effects of UVR on the skin. Additionally, although UVR induces endogenous cutaneous production of vitamin D, its damaging effects overshadow this positive benefit, especially in light of the ease of achieving recommended amounts of vitamin D through diet and supplementation. PMID:25207382

  5. Current State of Agile User-Centered Design: A Survey

    NASA Astrophysics Data System (ADS)

    Hussain, Zahid; Slany, Wolfgang; Holzinger, Andreas

    Agile software development methods are quite popular nowadays and are being adopted at an increasing rate in the industry every year. However, these methods are still lacking usability awareness in their development lifecycle, and the integration of usability/User-Centered Design (UCD) into agile methods is not adequately addressed. This paper presents the preliminary results of a recently conducted online survey regarding the current state of the integration of agile methods and usability/UCD. A world wide response of 92 practitioners was received. The results show that the majority of practitioners perceive that the integration of agile methods with usability/UCD has added value to their adopted processes and to their teams; has resulted in the improvement of usability and quality of the product developed; and has increased the satisfaction of the end-users of the product developed. The top most used HCI techniques are low-fidelity prototyping, conceptual designs, observational studies of users, usability expert evaluations, field studies, personas, rapid iterative testing, and laboratory usability testing.

  6. Ecopharmacovigilance: Current state, challenges, and opportunities in China.

    PubMed

    Wang, Jun; Hu, Xiamin

    2014-01-01

    In a context of severe pharmaceutical pollution, "ecopharmacovigilance" (EPV) has been an area of novel interest. It aims to ensure that significant environmental issues associated with pharmaceuticals in the environment are identified in a timely way, and managed appropriately. EPV has become a research hotspot as a comprehensive and boundary science in Europe and North America, and regulatory requirements governing the comprehensive environmental risk assessment (ERA) of pharmaceuticals exist in these regions. A speedy Chinese pharmaceutical industry development and drug consumption, China should shoulder more international responsibility and contribute to the worldwide EPV. Compared to the west, EPV in China is in its infancy. We analyzed the current state of EPV-related practice in China and found that many efforts have been made by the Chinese government and specialists to control the ever-worsening environmental pharmaceutical pollution problems, including consummating related policies and regulations, revealing the occurrence and behavior of pharmaceutical residues in environment and developing new technologies to improve their removal performance. Besides, we posed some recommendations on appropriate EPV implementation that can be taken with China in future. These include, building perfect laws and regulation system on EPV, defining the evaluation index for EPV, continuing the clinical rational medication and the pharmaceutical take-back programs in China, popularizing the concept of EPV in China, and strengthening the policy-guided and scientific researches of EPV in pharmaceutical firms and academia. PMID:24550578

  7. Current state and perspectives of truffle genetics and sustainable biotechnology.

    PubMed

    Poma, Anna; Limongi, Tania; Pacioni, Giovanni

    2006-09-01

    Mycorrhizal fungi belonging to the genus Tuber produce, after the establishment of a productive interaction with a plant host, hypogeous fruitbodies of great economic value known as ''truffles''. This review summarizes the state of art on life cycle, genetic, and biotechnological investigations of Tuber spp. The ascocarp formation in truffles is a consequence of the activation of the sexual phase of the biological cycle. The formation of a dikaryotic secondary mycelium and the karyogamy in the ascal cell (followed by meiosis with ascospores formation) have been hypothesized by several authors but some doubts yet arise from the Tuber cycle by considering that a series of abnormalities have been pointed out in respect to other Ascomycetes. It is unclear if binucleated hyphal cells are derived from the fusion of mononucleated cells belonging to mycelia from different mating types or from one only. According to the karyotypes of Tuber melanosporum, Tuber magnatum, and Tuber borchii, the numbers of hyphal chromosomes suggest a chromosome number of eight (2n); these values are in the range of those of several Ascomycetes and observed for Tuber aestivum (2n=10). The importance and growth in interest during the last years in the fungi protoplasts isolation and transformation techniques can be related to current developments in Tuber genetics and biotechnology. T. borchii could be transformed through liposome-mediated delivery of genetic material as mycelial protoplasts isolation and fusion with liposomes has already been established. On the other hand, Agrobacterium-mediated transformation has been successfully established for T. borchii. PMID:16802150

  8. Current state of genome-scale modeling in filamentous fungi.

    PubMed

    Brandl, Julian; Andersen, Mikael R

    2015-06-01

    The group of filamentous fungi contains important species used in industrial biotechnology for acid, antibiotics and enzyme production. Their unique lifestyle turns these organisms into a valuable genetic reservoir of new natural products and biomass degrading enzymes that has not been used to full capacity. One of the major bottlenecks in the development of new strains into viable industrial hosts is the alteration of the metabolism towards optimal production. Genome-scale models promise a reduction in the time needed for metabolic engineering by predicting the most potent targets in silico before testing them in vivo. The increasing availability of high quality models and molecular biological tools for manipulating filamentous fungi renders the model-guided engineering of these fungal factories possible with comprehensive metabolic networks. A typical fungal model contains on average 1138 unique metabolic reactions and 1050 ORFs, making them a vast knowledge-base of fungal metabolism. In the present review we focus on the current state as well as potential future applications of genome-scale models in filamentous fungi. PMID:25700817

  9. Current State of Value-Based Purchasing Programs.

    PubMed

    Chee, Tingyin T; Ryan, Andrew M; Wasfy, Jason H; Borden, William B

    2016-05-31

    The US healthcare system is rapidly moving toward rewarding value. Recent legislation, such as the Affordable Care Act and the Medicare Access and CHIP Reauthorization Act, solidified the role of value-based payment in Medicare. Many private insurers are following Medicare's lead. Much of the policy attention has been on programs such as accountable care organizations and bundled payments; yet, value-based purchasing (VBP) or pay-for-performance, defined as providers being paid fee-for-service with payment adjustments up or down based on value metrics, remains a core element of value payment in Medicare Access and CHIP Reauthorization Act and will likely remain so for the foreseeable future. This review article summarizes the current state of VBP programs and provides analysis of the strengths, weaknesses, and opportunities for the future. Multiple inpatient and outpatient VBP programs have been implemented and evaluated; the impact of those programs has been marginal. Opportunities to enhance the performance of VBP programs include improving the quality measurement science, strengthening both the size and design of incentives, reducing health disparities, establishing broad outcome measurement, choosing appropriate comparison targets, and determining the optimal role of VBP relative to alternative payment models. VBP programs will play a significant role in healthcare delivery for years to come, and they serve as an opportunity for providers to build the infrastructure needed for value-oriented care. PMID:27245648

  10. Ecopharmacovigilance: Current state, challenges, and opportunities in China

    PubMed Central

    Wang, Jun; Hu, Xiamin

    2014-01-01

    In a context of severe pharmaceutical pollution, “ecopharmacovigilance” (EPV) has been an area of novel interest. It aims to ensure that significant environmental issues associated with pharmaceuticals in the environment are identified in a timely way, and managed appropriately. EPV has become a research hotspot as a comprehensive and boundary science in Europe and North America, and regulatory requirements governing the comprehensive environmental risk assessment (ERA) of pharmaceuticals exist in these regions. A speedy Chinese pharmaceutical industry development and drug consumption, China should shoulder more international responsibility and contribute to the worldwide EPV. Compared to the west, EPV in China is in its infancy. We analyzed the current state of EPV-related practice in China and found that many efforts have been made by the Chinese government and specialists to control the ever-worsening environmental pharmaceutical pollution problems, including consummating related policies and regulations, revealing the occurrence and behavior of pharmaceutical residues in environment and developing new technologies to improve their removal performance. Besides, we posed some recommendations on appropriate EPV implementation that can be taken with China in future. These include, building perfect laws and regulation system on EPV, defining the evaluation index for EPV, continuing the clinical rational medication and the pharmaceutical take-back programs in China, popularizing the concept of EPV in China, and strengthening the policy-guided and scientific researches of EPV in pharmaceutical firms and academia. PMID:24550578

  11. Ebola hemorrhagic Fever and the current state of vaccine development.

    PubMed

    Hong, Joo Eun; Hong, Kee-Jong; Choi, Woo Young; Lee, Won-Ja; Choi, Yeon Hwa; Jeong, Chung-Hyeon; Cho, Kwang-Il

    2014-12-01

    Current Ebola virus outbreak in West Africa already reached the total number of 1,323 including 729 deaths by July 31st. the fatality is around 55% in the southeastern area of Guinea, Sierra Leone, Liberia, and Nigeria. The number of patients with Ebola Hemorrhagic Fever (EHF) was continuously increasing even though the any effective therapeutics or vaccines has not been developed yet. The Ebola virus in Guinea showed 98% homology with Zaire Ebola Virus. Study of the pathogenesis of Ebola virus infection and assess of the various candidates of vaccine have been tried for a long time, especially in United States and some European countries. Even though the attenuated live vaccine and DNA vaccine containing Ebola viral genes were tested and showed efficacy in chimpanzees, those candidates still need clinical tests requiring much longer time than the preclinical development to be approved for the practical treatment. It can be expected to eradicate Ebola virus by a safe and efficient vaccine development similar to the case of smallpox virus which was extinguished from the world by the variola vaccine. PMID:25562048

  12. Current Status of Liver Allocation in the United States.

    PubMed

    Elwir, Saleh; Lake, John

    2016-03-01

    The liver transplant allocation system is currently based upon the Model for End-Stage Liver Disease (MELD) score and allocates organs preferentially to patients with the highest scores (ie, the sickest patients) within a defined geographic unit. In addition, certain patient populations, such as patients with hepatocellular carcinoma and portopulmonary hypertension, receive MELD exception points to account for their increased waitlist mortality, which is not reflected by their MELD score. Significant geographic variation in the access to liver transplantation exists throughout the United States. Both the Organ Procurement and Transplant Network Board of Directors and the Health Resources and Services Administration have determined these geographic disparities to be unacceptable. The liver transplant community has worked to develop methods to reduce these geographic disparities and to reexamine how MELD exception points are granted to certain patient populations. As a result, numerous policy changes have been adopted throughout the years that have broadened the sharing of organs through wider geographic sharing. Despite all of these changes, variation in access to liver transplantation continues to exist, and, thus, the liver transplant community continues to examine new ways to address geographic disparities. This paper reviews several of the key changes to the liver allocation system that have occurred since the implementation of MELD allocation in 2002 and provides an overview of potential changes to the system. PMID:27231445

  13. Centipede Venom: Recent Discoveries and Current State of Knowledge

    PubMed Central

    Undheim, Eivind A. B.; Fry, Bryan G.; King, Glenn F.

    2015-01-01

    Centipedes are among the oldest extant venomous predators on the planet. Armed with a pair of modified, venom-bearing limbs, they are an important group of predatory arthropods and are infamous for their ability to deliver painful stings. Despite this, very little is known about centipede venom and its composition. Advances in analytical tools, however, have recently provided the first detailed insights into the composition and evolution of centipede venoms. This has revealed that centipede venom proteins are highly diverse, with 61 phylogenetically distinct venom protein and peptide families. A number of these have been convergently recruited into the venoms of other animals, providing valuable information on potential underlying causes of the occasionally serious complications arising from human centipede envenomations. However, the majority of venom protein and peptide families bear no resemblance to any characterised protein or peptide family, highlighting the novelty of centipede venoms. This review highlights recent discoveries and summarises the current state of knowledge on the fascinating venom system of centipedes. PMID:25723324

  14. Current state of the hydrothermal geochemistry studies at Cerro Prieto

    SciTech Connect

    Fausto L, J.J.; Jimenez S, M.E.; Esquer P, I.

    1981-01-01

    The current state of hydrothermal geochemistry studies being carried out at the field are reported. These studies are based on the results of chemical analysis of water samples collected during 1979 and 1980 at the geothermal wells of the area known as Cerro Prieto I, as well as from those located in the Cerro Prieto II and Cerro Prieto III areas, some of which have only recently started flowing. Data are presented on the chemical variations of the main chemical constituents dissolved in the waters, as well as on the Na/K and Na-K-Ca chemical relations and the temperatures calculated from them and from SiO/sub 2/. Fluid recharge into the reservoir and its direction of flow are interpreted from isotherm contour maps of the field prepared from Na/K and Na-K-Ca geothermometry and from concentration contour maps of some of the main chemical constituents. Well M-43 is discussed as an example of a well affected by well completion problems in its production casing. Its behavior is explained on the basis of the chemical characteristics of the produced water. The chemical changes that have taken place in some of the wells during production are explained by correlating the chemistry with the production mechanisms of the well (steam-water production rates).

  15. Biodiesel production--current state of the art and challenges.

    PubMed

    Vasudevan, Palligarnai T; Briggs, Michael

    2008-05-01

    Biodiesel is a clean-burning fuel produced from grease, vegetable oils, or animal fats. Biodiesel is produced by transesterification of oils with short-chain alcohols or by the esterification of fatty acids. The transesterification reaction consists of transforming triglycerides into fatty acid alkyl esters, in the presence of an alcohol, such as methanol or ethanol, and a catalyst, such as an alkali or acid, with glycerol as a byproduct. Because of diminishing petroleum reserves and the deleterious environmental consequences of exhaust gases from petroleum diesel, biodiesel has attracted attention during the past few years as a renewable and environmentally friendly fuel. Since biodiesel is made entirely from vegetable oil or animal fats, it is renewable and biodegradable. The majority of biodiesel today is produced by alkali-catalyzed transesterification with methanol, which results in a relatively short reaction time. However, the vegetable oil and alcohol must be substantially anhydrous and have a low free fatty acid content, because the presence of water or free fatty acid or both promotes soap formation. In this article, we examine different biodiesel sources (edible and nonedible), virgin oil versus waste oil, algae-based biodiesel that is gaining increasing importance, role of different catalysts including enzyme catalysts, and the current state-of-the-art in biodiesel production. PMID:18205018

  16. Ebola Hemorrhagic Fever and the Current State of Vaccine Development

    PubMed Central

    Hong, Joo Eun; Hong, Kee-Jong; Choi, Woo Young; Lee, Won-Ja; Choi, Yeon Hwa; Jeong, Chung-Hyeon; Cho, Kwang-il

    2014-01-01

    Current Ebola virus outbreak in West Africa already reached the total number of 1,323 including 729 deaths by July 31st. the fatality is around 55% in the southeastern area of Guinea, Sierra Leone, Liberia, and Nigeria. The number of patients with Ebola Hemorrhagic Fever (EHF) was continuously increasing even though the any effective therapeutics or vaccines has not been developed yet. The Ebola virus in Guinea showed 98% homology with Zaire Ebola Virus. Study of the pathogenesis of Ebola virus infection and assess of the various candidates of vaccine have been tried for a long time, especially in United States and some European countries. Even though the attenuated live vaccine and DNA vaccine containing Ebola viral genes were tested and showed efficacy in chimpanzees, those candidates still need clinical tests requiring much longer time than the preclinical development to be approved for the practical treatment. It can be expected to eradicate Ebola virus by a safe and efficient vaccine development similar to the case of smallpox virus which was extinguished from the world by the variola vaccine. PMID:25562048

  17. Centipede venom: recent discoveries and current state of knowledge.

    PubMed

    Undheim, Eivind A B; Fry, Bryan G; King, Glenn F

    2015-03-01

    Centipedes are among the oldest extant venomous predators on the planet. Armed with a pair of modified, venom-bearing limbs, they are an important group of predatory arthropods and are infamous for their ability to deliver painful stings. Despite this, very little is known about centipede venom and its composition. Advances in analytical tools, however, have recently provided the first detailed insights into the composition and evolution of centipede venoms. This has revealed that centipede venom proteins are highly diverse, with 61 phylogenetically distinct venom protein and peptide families. A number of these have been convergently recruited into the venoms of other animals, providing valuable information on potential underlying causes of the occasionally serious complications arising from human centipede envenomations. However, the majority of venom protein and peptide families bear no resemblance to any characterised protein or peptide family, highlighting the novelty of centipede venoms. This review highlights recent discoveries and summarises the current state of knowledge on the fascinating venom system of centipedes. PMID:25723324

  18. Deep Proteomics of Breast Cancer Cells Reveals that Metformin Rewires Signaling Networks Away from a Pro-growth State.

    PubMed

    Sacco, Francesca; Silvestri, Alessandra; Posca, Daniela; Pirrò, Stefano; Gherardini, Pier Federico; Castagnoli, Luisa; Mann, Matthias; Cesareni, Gianni

    2016-03-23

    Metformin is the most frequently prescribed drug for type 2 diabetes. In addition to its hypoglycemic effects, metformin also lowers cancer incidence. This anti-cancer activity is incompletely understood. Here, we profiled the metformin-dependent changes in the proteome and phosphoproteome of breast cancer cells using high-resolution mass spectrometry. In total, we quantified changes of 7,875 proteins and 15,813 phosphosites after metformin changes. To interpret these datasets, we developed a generally applicable strategy that overlays metformin-dependent changes in the proteome and phosphoproteome onto a literature-derived network. This approach suggested that metformin treatment makes cancer cells more sensitive to apoptotic stimuli and less sensitive to pro-growth stimuli. These hypotheses were tested in vivo; as a proof-of-principle, we demonstrated that metformin inhibits the p70S6K-rpS6 axis in a PP2A-phosphatase dependent manner. In conclusion, analysis of deep proteomics reveals both detailed and global mechanisms that contribute to the anti-cancer activity of metformin. PMID:27135362

  19. The Origins and Current State of Plastic Surgery Residency in the United States.

    PubMed

    Mackay, Donald Roy; Johnson, Shane

    2015-11-01

    The history of plastic surgery residency training in the United States dates back to the establishment of plastic surgery as a specialty. The pivotal role played by the American Board of Plastic Surgery is outlined. The history of the early regulatory bodies leading to the formation of the Accreditation Council for Graduate Medical Education and the Residency Review Committees and the establishment of the American Council of Academic Plastic Surgeons gives context to our current training models. PMID:26594962

  20. Genomes to Proteomes

    SciTech Connect

    Panisko, Ellen A.; Grigoriev, Igor; Daly, Don S.; Webb-Robertson, Bobbie-Jo; Baker, Scott E.

    2009-03-01

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

  1. Cardiovascular pharmacogenomics; state of current knowledge and implementation in practice.

    PubMed

    Shahabi, Payman; Dubé, Marie-Pierre

    2015-04-01

    Pharmacogenomics (PGx) is the science that examines how an individual's genetic make-up affects the safety and efficacy of therapeutic drugs. PGx of response to cardiovascular (CV) medications is of the most successfully translated branches of PGx into the clinical workout. However, the clinical implementation of PGx of CV drugs is yet far beyond the growth of our understanding of the role of genetics in drug therapy. A considerable amount of efforts have been devoted by the regulatory agents like the food and drug administration (FDA) as well as the expert-based networks such as the Clinical Pharmacogenetics Implementation Consortium (CPIC) to overcome the existing barriers. This has been done, at least in part, for some of the most widely prescribed CV drugs, including clopidogrel, warfarin and simvastatin for which the PGx knowledge have been satisfactorily robust to provoke the CPIC to issue the guidelines for these drugs and the FDA to update the drugs' labeling, both strongly recommended the use of genotype-guided dosing for these medications, provided that the genetic data are available. For other drugs, however, studies have produced contradictory results and further large and well-designed clinical trials are required to expand and confirm the clinical utility of their PGx data. This review paper presents the current state of knowledge in the field of PGx of CV medications and describes the facilities assisting to the translation of PGx data into the clinical practice. Afterward, the existing body of PGx literature of the most-commonly used CV medications is comprehensively discussed. PMID:25838112

  2. Current state of forest mapping with Landsat data in Siberia

    NASA Astrophysics Data System (ADS)

    Maksyutov, Shamil; Sedykh, Vladimir; Kuzmenko, Ekaterina; Farber, Sergey; Kalinicheva, Svetlana; Fedorov, Alexander; Schepaschenko, Dmitry

    2016-04-01

    We review a current state of a forest type mapping with Landsat data in Siberia. Target algorithm should be based on dynamic vegetation approach to be applicable to the analysis of the forest type distribution for Siberia, aiming at capability of mapping Siberian forest landscapes for applications such as predicting response of forest composition to climate change. We present data for several areas in West Siberian middle taiga, Central Siberia and East Siberia near Yakutsk. Analysis of the field survey, forest inventory data was made to produce forest type classification accounting for several stages for forest succession and variations in habitats and landforms. Supervised classification was applied to the areas were the ground truth and inventory data are available, including several limited area maps and vegetation survey transects. In Laryegan basin in West Siberia the upland forest areas are dominated by mix of Scots pine on sandy soils and Siberian pine with presence of fir and spruce on the others. Abundance of Scots pine decreases to the west due to change in soils. Those types are separable using Landsat spectral data. In the permafrost area around Yakutsk the most widespread succession type is birch to larch. Three stages of the birch to larch succession are detectable from Landsat image. When Landsat data is used in both West and East Siberia, distinction between deciduous broad-leaved species (birch, aspen, and willow) is generally difficult. Similar problem exist for distinguishing between dark coniferous species (Siberian pine, fir and spruce). Image classification can be improved by applying landform type analysis, such as separation into floodplain, terrace, sloping hills. Additional layers of information can be a promising way to complement Landsat data.

  3. Proteomics of Leaf Tissues from Populus

    SciTech Connect

    Hurst, Gregory {Greg} B; Yang, Xiaohan; Tschaplinski, Timothy J; Tuskan, Gerald A; Lankford, Patricia K; Shah, Manesh B; Jawdy, Sara; Gunter, Lee E; Engle, Nancy L

    2010-01-01

    Trees of the genus Populus are farmed commercially for wood and fiber, and are a potential bioenergy crop. As a scientific model organism, P. trichocarpa was the first forest tree for which the genome sequence has been determined. Knowledge of the Populus proteome will provide a deeper understanding of gene expression patterns in various tissues of the plant. To build on our previous profile of the proteome of xylem tissue in Populus (Kalluri et al., Proteomics 2009, 9, 4871), we are currently developing methods for studying the proteome of Populus leaves.

  4. Salivary biomarkers for detection of oral squamous cell carcinoma – current state and recent advances

    PubMed Central

    Yakob, Maha; Fuentes, Laurel; Wang, Marilene B.; Abemayor, Elliot; Wong, David T.W.

    2014-01-01

    Oral squamous cell carcinoma (OSCC) is the most common malignant neoplasm of the oral cavity. Detection of OSCC is currently based on thorough clinical oral examination combined with biopsy for histological analysis. Most cases of OSCC are not detected until the cancer has developed into advanced stages; thus, a reliable early stage diagnostic marker is needed. This literature review presents an overview of the status of current advances in salivary diagnostics for OSCC. Though many protein and mRNA salivary biomarkers have been identified that can detect OSCC with high sensitivity and specificity, the most discernable findings occur with the use of multiple markers. Studies that incorporate proteomic, transcriptomic, and potentially additional “omics”, including methylomics, need to be initiated to bring technology to clinical applications and allow the best use of saliva in diagnosing OSCC. PMID:24883261

  5. Evaluation of the Current State of Integrated Water Quality Modelling

    NASA Astrophysics Data System (ADS)

    Arhonditsis, G. B.; Wellen, C. C.; Ecological Modelling Laboratory

    2010-12-01

    Environmental policy and management implementation require robust methods for assessing the contribution of various point and non-point pollution sources to water quality problems as well as methods for estimating the expected and achieved compliance with the water quality goals. Water quality models have been widely used for creating the scientific basis for management decisions by providing a predictive link between restoration actions and ecosystem response. Modelling water quality and nutrient transport is challenging due a number of constraints associated with the input data and existing knowledge gaps related to the mathematical description of landscape and in-stream biogeochemical processes. While enormous effort has been invested to make watershed models process-based and spatially-distributed, there has not been a comprehensive meta-analysis of model credibility in watershed modelling literature. In this study, we evaluate the current state of integrated water quality modeling across the range of temporal and spatial scales typically utilized. We address several common modeling questions by providing a quantitative assessment of model performance and by assessing how model performance depends on model development. The data compiled represent a heterogeneous group of modeling studies, especially with respect to complexity, spatial and temporal scales and model development objectives. Beginning from 1992, the year when Beven and Binley published their seminal paper on uncertainty analysis in hydrological modelling, and ending in 2009, we selected over 150 papers fitting a number of criteria. These criteria involved publications that: (i) employed distributed or semi-distributed modelling approaches; (ii) provided predictions on flow and nutrient concentration state variables; and (iii) reported fit to measured data. Model performance was quantified with the Nash-Sutcliffe Efficiency, the relative error, and the coefficient of determination. Further, our

  6. The proteome of human saliva

    NASA Astrophysics Data System (ADS)

    Griffin, Timothy J.

    2013-05-01

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

  7. The Current State of Naïve Human Pluripotency

    PubMed Central

    Dodsworth, Benjamin T.; Flynn, Rowan

    2015-01-01

    Abstract Naïve or ground state pluripotency is a cellular state in vitro which resembles cells of the preimplantation epiblast in vivo. This state was first observed in mouse embryonic stem cells and is characterized by high rates of proliferation, the ability to differentiate widely, and global hypomethylation. Human pluripotent stem cells (hPSCs) correspond to a later or “primed” stage of embryonic development. The conversion of hPSCs to a naïve state is desirable as their features should facilitate techniques such as gene editing and more efficient differentiation. Here we review protocols which now allow derivation of naïve human pluripotent stem cells by transgene expression or the use of media formulations containing inhibitors and growth factors and correlate this with pathways involved. Maintenance of these ground state cells is possible using a combination of basic fibroblast growth factor and human leukemia inhibitory factor together with dual inhibition of glycogen synthase kinase 3 beta, and mitogen‐activated protein kinase kinase (MEK). Close similarity between the ground state hPSC and the in vivo preimplantation epiblast have been shown both by demonstrating similar upregulation of endogenous retroviruses and correlation of global RNA‐seq data. This suggests that the human naïve state is not an in vitro artifact. Stem Cells 2015;33:3181–3186 PMID:26119873

  8. Fault current limiter with solid-state circuit breakers

    NASA Astrophysics Data System (ADS)

    Bălan, H.; Neamț, L.; Buzdugan, M. I.; Varodi, T.; Pop, E.

    2016-08-01

    Switching of power circuit breakers is an important technical issue, especially at short circuit, since the fault current cause thermal and dynamic stresses, and the power quality worsens. Recently, the development of distributed renewable electricity induces the short circuit protection problematic because the distributed production of electric energy cause the transport networks to lose their radial character and disturbs the protective relays coordination. The modern technologies for power switching uses static fault current limiters, which offers a viable solution to remove the problems caused by large fault currents in the system. An appropriate design of the current limiting device reduces the thermal and dynamic stress and limits the fault current to a low value. The static switches are based on high power semiconductor devices that offer advantages compared to mechanical switches. Using a fault current limiter that minimizes the effect of distributed generation of electricity in a radial network on the co-ordination of protective relays is a solution to this problem in terms of switching speed and lifespan of power switches.

  9. Protein translation machinery holds a key for transition of planktonic cells to biofilm state in Enterococcus faecalis: A proteomic approach.

    PubMed

    Qayyum, Shariq; Sharma, Divakar; Bisht, Deepa; Khan, Asad U

    2016-06-10

    Enterococcus faecalis is a member of human gut microflora causing nosocomial infection involving biofilm formation. Ethyl methyl sulfonate induced mutants were analysed using crystal violet assay, SEM and CLSM microscopy which confirmed AK-E12 as biofilm efficient and AK-F6 as biofilm deficient mutants. Growth curve pattern revealed AK-E12 was fast growing whereas, AK-F6 was found slow growing mutant. 2D-Electrophorosis and MALDI-TOF analysis revealed over and underexpression of many translation-elongation associated proteins in mutants compared to wild type. Protein translation elongation factor G, translation elongation factor Tu and ribosomal subunit interface proteins were underexpressed and UTP-glucose-1-phosphate uridylyl transferase and cell division protein divIVA were overexpressed in AK-E12 as compared to wild type. In AK-F6, except 10 kDa chaperonin which was over-expressed other selected proteins were found to be suppressed. RT-PCR confirmed proteomic data except for the translation elongation factor G which showed contradictory data of proteome expression in AK-E12. Protein-protein interaction networks were constructed using STRING 10.0 which demonstrated strong connection of translation-elongation proteins with other proteins. Hence, it concludes from the data that translation elongation factors are important in transition of planktonic cells to biofilm cells in Enterococcus faecalis. PMID:27144316

  10. ProCon - PROteomics CONversion tool.

    PubMed

    Mayer, Gerhard; Stephan, Christian; Meyer, Helmut E; Kohl, Michael; Marcus, Katrin; Eisenacher, Martin

    2015-11-01

    With the growing amount of experimental data produced in proteomics experiments and the requirements/recommendations of journals in the proteomics field to publicly make available data described in papers, a need for long-term storage of proteomics data in public repositories arises. For such an upload one needs proteomics data in a standardized format. Therefore, it is desirable, that the proprietary vendor's software will integrate in the future such an export functionality using the standard formats for proteomics results defined by the HUPO-PSI group. Currently not all search engines and analysis tools support these standard formats. In the meantime there is a need to provide user-friendly free-to-use conversion tools that can convert the data into such standard formats in order to support wet-lab scientists in creating proteomics data files ready for upload into the public repositories. ProCon is such a conversion tool written in Java for conversion of proteomics identification data into standard formats mzIdentML and Pride XML. It allows the conversion of Sequest™/Comet .out files, of search results from the popular and often used ProteomeDiscoverer® 1.x (x=versions 1.1 to1.4) software and search results stored in the LIMS systems ProteinScape® 1.3 and 2.1 into mzIdentML and PRIDE XML. This article is part of a Special Issue entitled: Computational Proteomics. PMID:26182917

  11. Current Developments in Communications Law in the United States

    ERIC Educational Resources Information Center

    Hadl, Robert D.

    1973-01-01

    Article reviews some of the major developments in communications law in the United States in the past year (1972). Significant events are covered in the areas of cable television, television programming and domestic satelites. (Author)

  12. Current State of the U.S. Ethanol Industry

    SciTech Connect

    Urbanchuk, John

    2010-11-30

    The objective of this study is to provide a comprehensive overview of the state of the U.S. ethanol industry and to outline the major forces that will affect the development of the industry over the next decade.

  13. Current status of the state-and-transition framework

    Technology Transfer Automated Retrieval System (TEKTRAN)

    State-and-transition models (STM) have been widely adopted as a tool for explaining plant community dynamics and response to disturbance within rangeland ecosystems. Our understanding of the STM concepts has advanced substantially since they were introduced by Westoby et al. (1989) and modified by ...

  14. Adult Cigarette Smoking in the United States: Current Estimates

    MedlinePlus

    ... Report 2015;64(44):1233–40 [accessed 2016 Mar 14]. U.S. Department of Health and Human Services. ... Office on Smoking and Health, 2014 [accessed 2016 Mar 14]. Centers for Disease Control and Prevention . State ...

  15. High School Feedback: An Analysis of States' Current Efforts

    ERIC Educational Resources Information Center

    Data Quality Campaign, 2011

    2011-01-01

    There is increased demand from multiple stakeholders for information about K-12 students' success after high school. When this information is provided back to high schools, it is often referred to as "high school feedback" information. This working document captures knowledge about states' capacity to and progress in providing high school feedback…

  16. Current Status of Teacher Shortage in the United States.

    ERIC Educational Resources Information Center

    Capa, Yesim; Loadman, William E.; Bryant, B. J.

    Every year the American Association of Employment in Education (AAEE) conducts a survey of the status of teacher supply and demand in the United States. In 2001, the 25th annual survey sent a survey instrument to 1,265 teacher preparation institutions to study the supply side of teacher availability, and responses were received from 494…

  17. Current challenges in detecting food allergens by shotgun and targeted proteomic approaches: a case study on traces of peanut allergens in baked cookies.

    PubMed

    Pedreschi, Romina; Nørgaard, Jørgen; Maquet, Alain

    2012-02-01

    There is a need for selective and sensitive methods to detect the presence of food allergens at trace levels in highly processed food products. In this work, a combination of non-targeted and targeted proteomics approaches are used to illustrate the difficulties encountered in the detection of the major peanut allergens Ara h 1, Ara h 2 and Ara h 3 from a representative processed food matrix. Shotgun proteomics was employed for selection of the proteotypic peptides for targeted approaches via selective reaction monitoring. Peanut presence through detection of the proteotypic Ara h 3/4 peptides AHVQVVDSNGNR (m/z 432.5, 3+) and SPDIYNPQAGSLK (m/z 695.4, 2+) was confirmed and the developed method was able to detect peanut presence at trace levels (≥10 μg peanut g(-1) matrix) in baked cookies. PMID:22413066

  18. Current Challenges in Detecting Food Allergens by Shotgun and Targeted Proteomic Approaches: A Case Study on Traces of Peanut Allergens in Baked Cookies

    PubMed Central

    Pedreschi, Romina; Nørgaard, Jørgen; Maquet, Alain

    2012-01-01

    There is a need for selective and sensitive methods to detect the presence of food allergens at trace levels in highly processed food products. In this work, a combination of non-targeted and targeted proteomics approaches are used to illustrate the difficulties encountered in the detection of the major peanut allergens Ara h 1, Ara h 2 and Ara h 3 from a representative processed food matrix. Shotgun proteomics was employed for selection of the proteotypic peptides for targeted approaches via selective reaction monitoring. Peanut presence through detection of the proteotypic Ara h 3/4 peptides AHVQVVDSNGNR (m/z 432.5, 3+) and SPDIYNPQAGSLK (m/z 695.4, 2+) was confirmed and the developed method was able to detect peanut presence at trace levels (≥10 μg peanut g−1 matrix) in baked cookies. PMID:22413066

  19. Parasites, proteomes and systems: has Descartes’ clock run out of time?

    PubMed Central

    WASTLING, J. M.; ARMSTRONG, S. D.; KRISHNA, R.; XIA, D.

    2012-01-01

    SUMMARY Systems biology aims to integrate multiple biological data types such as genomics, transcriptomics and proteomics across different levels of structure and scale; it represents an emerging paradigm in the scientific process which challenges the reductionism that has dominated biomedical research for hundreds of years. Systems biology will nevertheless only be successful if the technologies on which it is based are able to deliver the required type and quality of data. In this review we discuss how well positioned is proteomics to deliver the data necessary to support meaningful systems modelling in parasite biology. We summarise the current state of identification proteomics in parasites, but argue that a new generation of quantitative proteomics data is now needed to underpin effective systems modelling. We discuss the challenges faced to acquire more complete knowledge of protein post-translational modifications, protein turnover and protein-protein interactions in parasites. Finally we highlight the central role of proteome-informatics in ensuring that proteomics data is readily accessible to the user-community and can be translated and integrated with other relevant data types. PMID:22828391

  20. Social validity assessments: is current practice state of the art?

    PubMed Central

    Schwartz, I S; Baer, D M

    1991-01-01

    The use of evaluative feedback from consumers to guide program planning and evaluation is often referred to as the assessment of social validity. Differing views of its role and value in applied behavior analysis have emerged, and increasingly stereotyped assessments of social validity are becoming commonplace. This paper argues that current applications of social validity assessments are straying from the point originally proposed for them. Thus, several suggestions for improving current social validity assessment are proposed, including (a) expanding the definition of consumers to acknowledge the variety of community members able and likely to affect a program's survival, (b) increasing the psychometric rigor of social validity assessments, (c) extending assessment to heretofore underrepresented populations, (d) implementing widespread application of well-designed social validity assessments, (e) increasing meaningful consumer involvement in the planning and evaluation of behavioral programs, and (f) educating consumers to make better informed programming decisions. PMID:1890040

  1. [Physiotherapeutic care marketing research: current state-of-the art].

    PubMed

    Babaskin, D V

    2011-01-01

    Successful introduction of modern technologies into the national health care systems strongly depends on the current pharmaceutical market situation. The present article is focused on the peculiarities of marketing research with special reference to physiotherapeutic services and commodities. Analysis of the structure and sequence of marketing research processes is described along with the methods applied for the purpose including their support by the use of Internet resources and technologies. PMID:21574299

  2. Minimally invasive veneers: current state of the art

    PubMed Central

    Vanlıoğlu, Burçin Akoğlu; Kulak-Özkan, Yasemin

    2014-01-01

    Ceramic veneers are considered a conservative solution for patients requiring improvement of the shape, color, or position of their anterior teeth. Ceramic veneers have been extensively and successfully used to mask intrinsic staining, to give the appearance of straightening, and to correct minor malformations of anterior teeth without the removal of substantial amounts of sound tooth substance. The current literature was reviewed to search for the most important parameters determining the long-term success and correct application of ceramic veneers. PMID:25506248

  3. Left ventricular assist devices-current state and perspectives.

    PubMed

    Prinzing, Anatol; Herold, Ulf; Berkefeld, Anna; Krane, Markus; Lange, Rüdiger; Voss, Bernhard

    2016-08-01

    Mechanical circulatory support devices have become an important treatment tool for severe acute and chronic heart failure, since heart transplantation cannot meet the demands because of a lack of available donor organs. Since implantation of the first ventricular assist device a constant development of the suitability of these devices has been made. This review will introduce different generations of left ventricular assist devices (LVAD) and elaborate on clinical indications, risk stratification and current literature. PMID:27621895

  4. Left ventricular assist devices—current state and perspectives

    PubMed Central

    Herold, Ulf; Berkefeld, Anna; Krane, Markus; Lange, Rüdiger; Voss, Bernhard

    2016-01-01

    Mechanical circulatory support devices have become an important treatment tool for severe acute and chronic heart failure, since heart transplantation cannot meet the demands because of a lack of available donor organs. Since implantation of the first ventricular assist device a constant development of the suitability of these devices has been made. This review will introduce different generations of left ventricular assist devices (LVAD) and elaborate on clinical indications, risk stratification and current literature. PMID:27621895

  5. Minimally invasive veneers: current state of the art.

    PubMed

    Vanlıoğlu, Burçin Akoğlu; Kulak-Özkan, Yasemin

    2014-01-01

    Ceramic veneers are considered a conservative solution for patients requiring improvement of the shape, color, or position of their anterior teeth. Ceramic veneers have been extensively and successfully used to mask intrinsic staining, to give the appearance of straightening, and to correct minor malformations of anterior teeth without the removal of substantial amounts of sound tooth substance. The current literature was reviewed to search for the most important parameters determining the long-term success and correct application of ceramic veneers. PMID:25506248

  6. State-of-the-art housekeeping proteins for quantitative western blotting: Revisiting the first draft of the human proteome.

    PubMed

    Lee, Hyun-Gwan; Jo, Jihoon; Hong, Hyun-Hee; Kim, Kee K; Park, Joong-Ki; Cho, Sung-Jin; Park, Chungoo

    2016-07-01

    Western blotting (WB) analysis is the most popular and widely used methodology for protein detection and characterization over recent decades. In accordance with the advancement of the technologies for the acquisition of WB signals, a quantitative value is used to present the abundance of target proteins in a complex sample, thereby requiring the use of specific proteins as internal references that represent total proteins. Heretofore, proteins encoded by housekeeping genes such as GAPDH, β-tubulin and β-actin have been commonly used as loading controls without any hesitation because their mRNA expression levels tend to be high and constant in many different cells and tissues. Experimentally, however, some of the housekeeping reference proteins are often displayed with inconsistent expression levels in both homogeneous and heterogeneous tissues, and, in terms of mRNA levels, they have a weak correlation to the abundance of proteins. To estimate accurate, reliable, and reproducible protein quantifications, it is crucial to define appropriate reference controls. For this paper, we explored the recently released large-scale, human proteomic database ProteomicsDB including 16 857 liquid chromatography tandem-mass-spectrometry data from 27 human tissues, and suggest 20 ubiquitously- and constitutively-expressed, putative internal-reference controls for the quantification of differential protein expressions. Intriguingly, the most commonly used, known housekeeping genes were entirely excluded in our newly defined candidates. Although the applications of the candidates under many different biological conditions and in other organisms are yet to be empirically verified, we propose reliable, potential loading controls for a WB analysis in this paper. PMID:27125885

  7. Melanoma control in the United States: current status.

    PubMed

    Koh, H K; Geller, A C

    1995-01-01

    Screening and education for melanoma/skin cancer are receiving increasing worldwide attention. In an attempt to improve melanoma control in the United States, where incidence and mortality rates continue to increase, the American Academy of Dermatology (AAD) has provided free skin cancer screenings to more than 600,000 Americans and prevention messages to millions more. This chapter reviews and summarizes ongoing melanoma control activities in the United States, including prevention, education, and early detection/screening. We also address outcome measures in melanoma control and suggest that the unique external and visible nature of skin cancer blurs the distinction between screening and education. Measuring and evaluating the benefits of international melanoma control activities presents many challenging tasks. Future collaborative work must include complementary strategies in melanoma/skin cancer prevention, education, and screening to combat the worldwide increase in melanoma incidence and mortality. PMID:7597293

  8. Current trends in suicidal behavior in the United States.

    PubMed

    Frederick, C J

    1978-04-01

    Suicidal behavior in the United States from 1900 to 1975 is reviewed. The data presented cover demographic variables such as: age, sex, color, and geographic area. While the overall suicide rate continues to increase, the most striking upturn can be seen in both sexes between the ages of 15 to 25 years. The need for a wide range of innovative approaches and increased research is manifest. PMID:677350

  9. State Poverty-Based Education Funding: A Survey of Current Programs and Options for Improvement.

    ERIC Educational Resources Information Center

    Carey, Kevin

    This paper describes the current status of state poverty-based education funding programs, discussing how to implement or improve them. Researchers surveyed education finance officials in the 49 states with multiple school districts. Results indicate that 38 states currently distribute some education funds on the basis of poverty. A total of 75…

  10. Miniature x-ray tubes: current state and future prospects

    NASA Astrophysics Data System (ADS)

    Filip, V.; Filip, L. D.; Okuyama, F.

    2013-03-01

    Over the last decade, field emission miniature x-ray tubes emerged as cutting-edge applications of nanotechnology, possessing massive potential for use in various important fields, including that of precision medical therapy. The article essentially presents a review of such new devices reported in the literature. Additional discussions on the necessity of stabilizing the electron beam that generates x-rays are also included, and a simple technique for minimizing the current fluctuations is described. It is also pointed out that further miniaturization of field emission x-ray sources may need new concepts in designing the tube in shapes acting as ``self focusing'' structures for the electron beams.

  11. Cell death proteomics database: consolidating proteomics data on cell death.

    PubMed

    Arntzen, Magnus Ø; Bull, Vibeke H; Thiede, Bernd

    2013-05-01

    Programmed cell death is a ubiquitous process of utmost importance for the development and maintenance of multicellular organisms. More than 10 different types of programmed cell death forms have been discovered. Several proteomics analyses have been performed to gain insight in proteins involved in the different forms of programmed cell death. To consolidate these studies, we have developed the cell death proteomics (CDP) database, which comprehends data from apoptosis, autophagy, cytotoxic granule-mediated cell death, excitotoxicity, mitotic catastrophe, paraptosis, pyroptosis, and Wallerian degeneration. The CDP database is available as a web-based database to compare protein identifications and quantitative information across different experimental setups. The proteomics data of 73 publications were integrated and unified with protein annotations from UniProt-KB and gene ontology (GO). Currently, more than 6,500 records of more than 3,700 proteins are included in the CDP. Comparing apoptosis and autophagy using overrepresentation analysis of GO terms, the majority of enriched processes were found in both, but also some clear differences were perceived. Furthermore, the analysis revealed differences and similarities of the proteome between autophagosomal and overall autophagy. The CDP database represents a useful tool to consolidate data from proteome analyses of programmed cell death and is available at http://celldeathproteomics.uio.no. PMID:23537399

  12. Proteomic profiling of lymphocytes in autoimmunity, inflammation and cancer

    PubMed Central

    2014-01-01

    Lymphocytes play important roles in the balance between body defense and noxious agents involved in a number of diseases, e.g. autoimmune diseases, allergic inflammation and cancer. The proteomic analyses have been applied to identify and validate disease-associated and disease-specific biomarkers for therapeutic strategies of diseases. The proteomic profiles of lymphocytes may provide more information to understand their functions and roles in the development of diseases, although proteomic approaches in lymphocytes are still limited. The present review overviewed the proteomics-based studies on lymphocytes to headlight the proteomic profiles of lymphocytes in diseases, such as autoimmune diseases, allergic inflammation and cancer, with a special focus on lung diseases. We will explore the potential significance of diagnostic biomarkers and therapeutic targets from the current status in proteomic studies of lymphocytes and discuss the value of the currently available proteomic methodologies in the lymphocytes research. PMID:24397796

  13. Imaging of HCC-Current State of the Art.

    PubMed

    Schraml, Christina; Kaufmann, Sascha; Rempp, Hansjoerg; Syha, Roland; Ketelsen, Dominik; Notohamiprodjo, Mike; Nikolaou, Konstantin

    2015-01-01

    Early diagnosis of hepatocellular carcinoma (HCC) is crucial for optimizing treatment outcome. Ongoing advances are being made in imaging of HCC regarding detection, grading, staging, and also treatment monitoring. This review gives an overview of the current international guidelines for diagnosing HCC and their discrepancies as well as critically summarizes the role of magnetic resonance imaging (MRI) and computed tomography (CT) techniques for imaging in HCC. The diagnostic performance of MRI with nonspecific and hepatobililiary contrast agents and the role of functional imaging with diffusion-weighted imaging will be discussed. On the other hand, CT as a fast, cheap and easily accessible imaging modality plays a major role in the clinical routine work-up of HCC. Technical advances in CT, such as dual energy CT and volume perfusion CT, are currently being explored for improving detection, characterization and staging of HCC with promising results. Cone beam CT can provide a three-dimensional analysis of the liver with tumor and vessel characterization comparable to cross-sectional imaging so that this technique is gaining an increasing role in the peri-procedural imaging of HCC treated with interventional techniques. PMID:26854169

  14. Bassoonists' medical problems-current state of knowledge.

    PubMed

    Dawson, William J

    2012-06-01

    Specific musical instruments can be a source of physical problems to their players. Based on reviews of the literature and personal experience, this paper summarizes current knowledge of problems affecting musicians who play instruments in the bassoon family (including the bassoon, contrabassoon, and several other instruments). Prevalence rates are higher in reports of surveys (ranging up to 86%), compared to clinical reports of patients seen and treated. Significant risk factors include young age, small body size, female gender, and use of large instruments. Problems unique to bassoonists are rare; most physical difficulties also are seen in general musculoskeletal clinical practices and in musicians playing all types of instruments. The left upper extremity is more commonly affected by overuse-related conditions in bassoonists. Non-playing-related problems are equally important for consideration (such as degenerative disorders and acute trauma), since they also affect practice and performance. Little experimental data exist to validate current and widely-held principles of treatment, rehabilitation, and prevention. PMID:22739824

  15. Pediatric Heart Failure: Current State and Future Possibilities

    PubMed Central

    Jang, Gi Young

    2015-01-01

    Heart failure is a complex pathophysiological syndrome that can occur in children from a variety of diseases, including cardiomyopathies, myocarditis, and congenital heart disease. The condition is associated with a high rate of morbidity and mortality and places a significant burden on families of affected children and to society as a whole. Current medical therapy is taken largely from the management of heart failure in adults, though clear survival benefit of these medications are lacking. Ventricular assist devices (VADs) have taken an increasingly important role in the management of advanced heart failure in children. The predominant role of these devices has been as a bridge to heart transplantation, and excellent results are currently achieved for most children with cardiomyopathies. There is an ongoing investigation to improve outcomes in high-risk populations, such as small infants and those with complex congenital heart disease, including patients with functionally univentricular hearts. Additionally, there is an active investigation and interest in expansion of VADs beyond the predominant utilization as a bridge to a heart transplant into ventricular recovery, device explant without a heart transplantation (bridge to recovery), and placement of devices without the expectation of recovery or transplantation (destination therapy). PMID:25653697

  16. Advanced Imaging in Femoroacetabular Impingement: Current State and Future Prospects

    PubMed Central

    Bittersohl, Bernd; Hosalkar, Harish S.; Hesper, Tobias; Tiderius, Carl Johan; Zilkens, Christoph; Krauspe, Rüdiger

    2015-01-01

    Symptomatic femoroacetabular impingement (FAI) is now a known precursor of early osteoarthritis (OA) of the hip. In terms of clinical intervention, the decision between joint preservation and joint replacement hinges on the severity of articular cartilage degeneration. The exact threshold during the course of disease progression when the cartilage damage is irreparable remains elusive. The intention behind radiographic imaging is to accurately identify the morphology of osseous structural abnormalities and to accurately characterize the chondrolabral damage as much as possible. However, both plain radiographs and computed tomography (CT) are insensitive for articular cartilage anatomy and pathology. Advanced magnetic resonance imaging (MRI) techniques include magnetic resonance arthrography and biochemically sensitive techniques of delayed gadolinium-enhanced MRI of cartilage (dGEMRIC), T1rho (T1ρ), T2/T2* mapping, and several others. The diagnostic performance of these techniques to evaluate cartilage degeneration could improve the ability to predict an individual patient-specific outcome with non-surgical and surgical care. This review discusses the facts and current applications of biochemical MRI for hip joint cartilage assessment covering the roles of dGEMRIC, T2/T2*, and T1ρ mapping. The basics of each technique and their specific role in FAI assessment are outlined. Current limitations and potential pitfalls as well as future directions of biochemical imaging are also outlined. PMID:26258129

  17. Advanced Imaging in Femoroacetabular Impingement: Current State and Future Prospects.

    PubMed

    Bittersohl, Bernd; Hosalkar, Harish S; Hesper, Tobias; Tiderius, Carl Johan; Zilkens, Christoph; Krauspe, Rüdiger

    2015-01-01

    Symptomatic femoroacetabular impingement (FAI) is now a known precursor of early osteoarthritis (OA) of the hip. In terms of clinical intervention, the decision between joint preservation and joint replacement hinges on the severity of articular cartilage degeneration. The exact threshold during the course of disease progression when the cartilage damage is irreparable remains elusive. The intention behind radiographic imaging is to accurately identify the morphology of osseous structural abnormalities and to accurately characterize the chondrolabral damage as much as possible. However, both plain radiographs and computed tomography (CT) are insensitive for articular cartilage anatomy and pathology. Advanced magnetic resonance imaging (MRI) techniques include magnetic resonance arthrography and biochemically sensitive techniques of delayed gadolinium-enhanced MRI of cartilage (dGEMRIC), T1rho (T1ρ), T2/T2* mapping, and several others. The diagnostic performance of these techniques to evaluate cartilage degeneration could improve the ability to predict an individual patient-specific outcome with non-surgical and surgical care. This review discusses the facts and current applications of biochemical MRI for hip joint cartilage assessment covering the roles of dGEMRIC, T2/T2*, and T1ρ mapping. The basics of each technique and their specific role in FAI assessment are outlined. Current limitations and potential pitfalls as well as future directions of biochemical imaging are also outlined. PMID:26258129

  18. Current state of herbicides in herbicide-resistant crops.

    PubMed

    Green, Jerry M

    2014-09-01

    Current herbicide and herbicide trait practices are changing in response to the rapid spread of glyphosate-resistant weeds. Growers urgently needed glyphosate when glyphosate-resistant crops became available because weeds were becoming widely resistant to most commonly used selective herbicides, making weed management too complex and time consuming for large farm operations. Glyphosate made weed management easy and efficient by controlling all emerged weeds at a wide range of application timings. However, the intensive use of glyphosate over wide areas and concomitant decline in the use of other herbicides led eventually to the widespread evolution of weeds resistant to glyphosate. Today, weeds that are resistant to glyphosate and other herbicide types are threatening current crop production practices. Unfortunately, all commercial herbicide modes of action are over 20 years old and have resistant weed problems. The severity of the problem has prompted the renewal of efforts to discover new weed management technologies. One technology will be a new generation of crops with resistance to glyphosate, glufosinate and other existing herbicide modes of action. Other technologies will include new chemical, biological, cultural and mechanical methods for weed management. From the onset of commercialization, growers must now preserve the utility of new technologies by integrating their use with other weed management technologies in diverse and sustainable systems. PMID:24446395

  19. Imaging of HCC—Current State of the Art

    PubMed Central

    Schraml, Christina; Kaufmann, Sascha; Rempp, Hansjoerg; Syha, Roland; Ketelsen, Dominik; Notohamiprodjo, Mike; Nikolaou, Konstantin

    2015-01-01

    Early diagnosis of hepatocellular carcinoma (HCC) is crucial for optimizing treatment outcome. Ongoing advances are being made in imaging of HCC regarding detection, grading, staging, and also treatment monitoring. This review gives an overview of the current international guidelines for diagnosing HCC and their discrepancies as well as critically summarizes the role of magnetic resonance imaging (MRI) and computed tomography (CT) techniques for imaging in HCC. The diagnostic performance of MRI with nonspecific and hepatobililiary contrast agents and the role of functional imaging with diffusion-weighted imaging will be discussed. On the other hand, CT as a fast, cheap and easily accessible imaging modality plays a major role in the clinical routine work-up of HCC. Technical advances in CT, such as dual energy CT and volume perfusion CT, are currently being explored for improving detection, characterization and staging of HCC with promising results. Cone beam CT can provide a three-dimensional analysis of the liver with tumor and vessel characterization comparable to cross-sectional imaging so that this technique is gaining an increasing role in the peri-procedural imaging of HCC treated with interventional techniques. PMID:26854169

  20. Mining the plasma proteome for disease applications across seven logs of protein abundance.

    PubMed

    Zhang, Q; Faca, V; Hanash, S

    2011-01-01

    The current state of proteomics technologies has sufficiently advanced to allow in-depth quantitative analysis of the plasma proteome and development of a related knowledge base. Here we review approaches that have been applied to increase depth of analysis by mass spectrometry given the substantial complexity of plasma and the vast dynamic range of protein abundance. Fractionation strategies resulting in reduced complexity of individual fractions followed by mass spectrometry analysis of digests from individual fractions has allowed well in excess of 1000 proteins to be identified and quantified with high confidence that span more than seven logs of protein abundance. Such depth of analysis has contributed to elucidation of plasma proteome variation in health and of protein changes associated with disease states. PMID:21062094

  1. Current state of the art of vision based SLAM

    NASA Astrophysics Data System (ADS)

    Muhammad, Naveed; Fofi, David; Ainouz, Samia

    2009-02-01

    The ability of a robot to localise itself and simultaneously build a map of its environment (Simultaneous Localisation and Mapping or SLAM) is a fundamental characteristic required for autonomous operation of the robot. Vision Sensors are very attractive for application in SLAM because of their rich sensory output and cost effectiveness. Different issues are involved in the problem of vision based SLAM and many different approaches exist in order to solve these issues. This paper gives a classification of state-of-the-art vision based SLAM techniques in terms of (i) imaging systems used for performing SLAM which include single cameras, stereo pairs, multiple camera rigs and catadioptric sensors, (ii) features extracted from the environment in order to perform SLAM which include point features and line/edge features, (iii) initialisation of landmarks which can either be delayed or undelayed, (iv) SLAM techniques used which include Extended Kalman Filtering, Particle Filtering, biologically inspired techniques like RatSLAM, and other techniques like Local Bundle Adjustment, and (v) use of wheel odometry information. The paper also presents the implementation and analysis of stereo pair based EKF SLAM for synthetic data. Results prove the technique to work successfully in the presence of considerable amounts of sensor noise. We believe that state of the art presented in the paper can serve as a basis for future research in the area of vision based SLAM. It will permit further research in the area to be carried out in an efficient and application specific way.

  2. Mobile-health: A review of current state in 2015.

    PubMed

    Silva, Bruno M C; Rodrigues, Joel J P C; de la Torre Díez, Isabel; López-Coronado, Miguel; Saleem, Kashif

    2015-08-01

    Health telematics is a growing up issue that is becoming a major improvement on patient lives, especially in elderly, disabled, and chronically ill. In recent years, information and communication technologies improvements, along with mobile Internet, offering anywhere and anytime connectivity, play a key role on modern healthcare solutions. In this context, mobile health (m-Health) delivers healthcare services, overcoming geographical, temporal, and even organizational barriers. M-Health solutions address emerging problems on health services, including, the increasing number of chronic diseases related to lifestyle, high costs of existing national health services, the need to empower patients and families to self-care and handle their own healthcare, and the need to provide direct access to health services, regardless of time and place. Then, this paper presents a comprehensive review of the state of the art on m-Health services and applications. It surveys the most significant research work and presents a deep analysis of the top and novel m-Health services and applications proposed by industry. A discussion considering the European Union and United States approaches addressing the m-Health paradigm and directives already published is also considered. Open and challenging issues on emerging m-Health solutions are proposed for further works. PMID:26071682

  3. Invited review: Current state of genetic improvement in dairy sheep.

    PubMed

    Carta, A; Casu, Sara; Salaris, S

    2009-12-01

    Dairy sheep have been farmed traditionally in the Mediterranean basin in southern Europe, central Europe, eastern Europe, and in Near East countries. Currently, dairy sheep farming systems vary from extensive to intensive according to the economic relevance of the production chain and the specific environment and breed. Modern breeding programs were conceived in the 1960s. The most efficient selection scheme for local dairy sheep breeds is based on pyramidal management of the population with the breeders of nucleus flocks at the top, where pedigree and official milk recording, artificial insemination, controlled natural mating, and breeding value estimation are carried out to generate genetic progress. The genetic progress is then transferred to the commercial flocks through artificial insemination or natural-mating rams. Increasing milk yield is still the most profitable breeding objective for several breeds. Almost all milk is used for cheese production and, consequently, milk content traits are very important. Moreover, other traits are gaining interest for selection: machine milking ability and udder morphology, resistance to diseases (mastitis, internal parasites, scrapie), and traits related to the nutritional value of milk (fatty acid composition). Current breeding programs based on the traditional quantitative approach have achieved appreciable genetic gains for milk yield. In many cases, further selection goals such as milk composition, udder morphology, somatic cell count, and scrapie resistance have been implemented. However, the possibility of including other traits of selective interest is limited by high recording costs. Also, the organizational effort needed to apply the traditional quantitative approach limits the diffusion of current selection programs outside the European Mediterranean area. In this context, the application of selection schemes assisted by molecular information, to improve either traditional dairy traits or traits costly to record

  4. Quantum coherence of the molecular states and their corresponding currents in nanoscale Aharonov-Bohm interferometers

    NASA Astrophysics Data System (ADS)

    Liu, Jian-Heng; Tu, Matisse Wei-Yuan; Zhang, Wei-Min

    2016-07-01

    By considering a nanoscale Aharonov-Bohm (AB) interferometer consisting of a laterally coupled double dot coupled to the source and drain electrodes, we investigate the AB phase dependence of the bonding and antibonding states and the transport currents via the bonding and antibonding state channels. The relations of the AB phase dependence between the quantum states and the associated transport current components are analyzed, which provides useful information for the reconstruction of quantum states through the measurement of the transport current in such systems. We also obtain the validity of the experimental analysis [given in T. Hatano et al., Phys. Rev. Lett. 106, 076801 (2011), 10.1103/PhysRevLett.106.076801] that bonding state currents in different energy configurations are almost the same. With the coherent properties in the quantum dot states as well as in the transport currents, we also provide a way to manipulate the bonding and antibonding states through the AB magnetic flux.

  5. Sediments Contamination with Organic Micropollutants: Current State and Perspectives

    NASA Astrophysics Data System (ADS)

    Popenda, Agnieszka; Włodarczyk-Makuła, Maria

    2016-06-01

    This study focused on the sediment contamination with some organic micropollutants based on the monitoring data together with available literature in Poland. The following persistent organic pollutants (POPs): polycyclic aromatic hydrocarbons (PAHs), polychlorinated biphenyls (PCBs) and chlorinated pesticides (CP) were characterized in sediments with respect to current legislations in force. Based on accessible data, higher PAHs, PCBs and CP concentrations were found in river sediments than in lake sediments. Especially, sediments of the Oder River and its tributary in the southern part of Poland, were highly polluted. In order to minimize the risk of the secondary pollution of surface waters, it is necessary to introduce consolidated management system with sediments proceeding. Furthermore, it is also of great importance to elaborate specific regulations concerning conditions of sediments management.

  6. Renewable energy sources in Bulgaria: Current state and trends

    NASA Astrophysics Data System (ADS)

    Kolev, K.

    The over-dependency of Bulgaria on imported fuel stressed the importance of developing a new energy strategy based on energy saving which includes also using renewable energy sources (RES). The target is the substitution of at least 2 percent of the real primary energy consumption with RES by 2010. The author gives a generalized analysis of the available RES in Bulgaria -solar, wind, geothermal, biomass and mini-hydraulic. The potentialities of each source for its usage as a suitable energy supply are pointed out, as well as the current status of research and implementation work, problems connected with legislation, financing and production of particular facilities. The governmental policy concerning RES is considered briefly. A description is given to the project 'Technical and Economical Assessment of Possibilities for Expansion of the RES-part in the Energy Balance of the Country' developed and started in 1994 in the framework of the PHARE program.

  7. Cyanobactins from Cyanobacteria: Current Genetic and Chemical State of Knowledge

    PubMed Central

    Martins, Joana; Vasconcelos, Vitor

    2015-01-01

    Cyanobacteria are considered to be one of the most promising sources of new, natural products. Apart from non-ribosomal peptides and polyketides, ribosomally synthesized and post-translationally modified peptides (RiPPs) are one of the leading groups of bioactive compounds produced by cyanobacteria. Among these, cyanobactins have sparked attention due to their interesting bioactivities and for their potential to be prospective candidates in the development of drugs. It is assumed that the primary source of cyanobactins is cyanobacteria, although these compounds have also been isolated from marine animals such as ascidians, sponges and mollusks. The aim of this review is to update the current knowledge of cyanobactins, recognized as being produced by cyanobacteria, and to emphasize their genetic clusters and chemical structures as well as their bioactivities, ecological roles and biotechnological potential. PMID:26580631

  8. Living donor liver transplantation in Brazil-current state.

    PubMed

    Andraus, Wellington; Canedo, Bernardo F; D'Alburquerque, Luiz A C

    2016-04-01

    Currently in Brazil, living donor liver transplantation (LDLT) represents 8.5% of liver transplantation (LT), being the majority pediatric one. Up to now, according to Brazilian Organ Transplantation Association (ABTO) annual report, 2,086 procedures have been done nationwide, most of them in southeast and south regions. Based on national centers reports, biliary complication is the most common recipient postoperative complication (14.5-20.6%), followed by hepatic artery thrombosis (3.1-10.7%) and portal vein thrombosis (2.3-9.1%). Patient and graft overall 5-y survival correspond to 76% and 74%, respectively. Regarding the donor, morbidity rate ranges from 12.4% to 28.3%, with a national mortality rate of 0.14%. In conclusion, Brazilian LDLT programs enhance international experience that this is a feasible and safe procedure, as well as an excellent alternative strategy to overcome organs shortage. PMID:27115012

  9. The current state of prostate-specific antigen testing.

    PubMed

    Lewis, Ryan; Hornberger, Brad

    2016-09-01

    Since prostate-specific antigen (PSA) testing was approved in 1994, the incidence of metastasis and mortality from prostate cancer have significantly decreased. However, PSA screening for prostate cancer has limitations and few large randomized controlled trials have been conducted to determine the mortality benefit of PSA screening. Two studies that have been conducted are the Prostate, Lung, Colorectal, and Ovarian (PLCO) screening trial and the European Randomized Study of Screening for Prostate Cancer (ERSPC). These were the two main studies the US Preventive Services Task Force (USPSTF) used in its recommendation against prostate cancer screening in 2012. However, new evidence has demonstrated that the PLCO trial had significant limitations and the results of the ERSPC trial were more significant than previously thought. This article describes the strengths and weaknesses of the USPSTF's recommendation, along with current guidelines for prostate cancer screening. PMID:27575906

  10. Living donor liver transplantation in Brazil—current state

    PubMed Central

    Andraus, Wellington; D’Alburquerque, Luiz A. C.

    2016-01-01

    Currently in Brazil, living donor liver transplantation (LDLT) represents 8.5% of liver transplantation (LT), being the majority pediatric one. Up to now, according to Brazilian Organ Transplantation Association (ABTO) annual report, 2,086 procedures have been done nationwide, most of them in southeast and south regions. Based on national centers reports, biliary complication is the most common recipient postoperative complication (14.5–20.6%), followed by hepatic artery thrombosis (3.1–10.7%) and portal vein thrombosis (2.3–9.1%). Patient and graft overall 5-y survival correspond to 76% and 74%, respectively. Regarding the donor, morbidity rate ranges from 12.4% to 28.3%, with a national mortality rate of 0.14%. In conclusion, Brazilian LDLT programs enhance international experience that this is a feasible and safe procedure, as well as an excellent alternative strategy to overcome organs shortage. PMID:27115012

  11. Cyanobactins from Cyanobacteria: Current Genetic and Chemical State of Knowledge.

    PubMed

    Martins, Joana; Vasconcelos, Vitor

    2015-11-01

    Cyanobacteria are considered to be one of the most promising sources of new, natural products. Apart from non-ribosomal peptides and polyketides, ribosomally synthesized and post-translationally modified peptides (RiPPs) are one of the leading groups of bioactive compounds produced by cyanobacteria. Among these, cyanobactins have sparked attention due to their interesting bioactivities and for their potential to be prospective candidates in the development of drugs. It is assumed that the primary source of cyanobactins is cyanobacteria, although these compounds have also been isolated from marine animals such as ascidians, sponges and mollusks. The aim of this review is to update the current knowledge of cyanobactins, recognized as being produced by cyanobacteria, and to emphasize their genetic clusters and chemical structures as well as their bioactivities, ecological roles and biotechnological potential. PMID:26580631

  12. Current State of Vascular Resections in Pancreatic Cancer Surgery

    PubMed Central

    Hackert, Thilo; Schneider, Lutz; Büchler, Markus W.

    2015-01-01

    Pancreatic cancer (PDAC) is the fourth leading cause of cancer-related mortality in the Western world and, even in 2014, a therapeutic challenge. The only chance for long-term survival is radical surgical resection followed by adjuvant chemotherapy which can be performed in about 20% of all PDAC patients by the time of diagnosis. As pancreatic surgery has significantly changed during the past years, extended operations, including vascular resections, have become more frequently performed in specialized centres and the border of resectability has been pushed forward to achieve a potentially curative approach in the respective patients in combination with neoadjuvant and adjuvant treatment strategies. In contrast to adjuvant treatment which has to be regarded as a cornerstone to achieve long-term survival after resection, neoadjuvant treatment strategies for locally advanced findings are currently under debate. This overview summarizes the possibilities and evidence of vascular, namely, venous and arterial, resections in PDAC surgery. PMID:26609306

  13. Scientific Workflow Management in Proteomics

    PubMed Central

    de Bruin, Jeroen S.; Deelder, André M.; Palmblad, Magnus

    2012-01-01

    Data processing in proteomics can be a challenging endeavor, requiring extensive knowledge of many different software packages, all with different algorithms, data format requirements, and user interfaces. In this article we describe the integration of a number of existing programs and tools in Taverna Workbench, a scientific workflow manager currently being developed in the bioinformatics community. We demonstrate how a workflow manager provides a single, visually clear and intuitive interface to complex data analysis tasks in proteomics, from raw mass spectrometry data to protein identifications and beyond. PMID:22411703

  14. Poliomyelitis in the United States: A Historical Perspective and Current Vaccination Policy.

    ERIC Educational Resources Information Center

    Farizo, Karen M.; And Others

    1990-01-01

    Examines poliomyelitis in the United States by reviewing clinical manifestations and outcomes, history, recent epidemiologic characteristics, characteristics of currently available vaccines, controversies surrounding vaccination policy, current poliovirus vaccination recommendations, and prospects for worldwide eradication. Poliomyelitis remains…

  15. Computer-Assisted Orthopedic Surgery: Current State and Future Perspective

    PubMed Central

    Zheng, Guoyan; Nolte, Lutz P.

    2015-01-01

    Introduced about two decades ago, computer-assisted orthopedic surgery (CAOS) has emerged as a new and independent area, due to the importance of treatment of musculoskeletal diseases in orthopedics and traumatology, increasing availability of different imaging modalities, and advances in analytics and navigation tools. The aim of this paper is to present the basic elements of CAOS devices and to review state-of-the-art examples of different imaging modalities used to create the virtual representations, of different position tracking devices for navigation systems, of different surgical robots, of different methods for registration and referencing, and of CAOS modules that have been realized for different surgical procedures. Future perspectives will also be outlined. PMID:26779486

  16. Computer-Assisted Orthopedic Surgery: Current State and Future Perspective.

    PubMed

    Zheng, Guoyan; Nolte, Lutz P

    2015-01-01

    Introduced about two decades ago, computer-assisted orthopedic surgery (CAOS) has emerged as a new and independent area, due to the importance of treatment of musculoskeletal diseases in orthopedics and traumatology, increasing availability of different imaging modalities, and advances in analytics and navigation tools. The aim of this paper is to present the basic elements of CAOS devices and to review state-of-the-art examples of different imaging modalities used to create the virtual representations, of different position tracking devices for navigation systems, of different surgical robots, of different methods for registration and referencing, and of CAOS modules that have been realized for different surgical procedures. Future perspectives will also be outlined. PMID:26779486

  17. Phenotypic Variability in Resting-State Functional Connectivity: Current Status

    PubMed Central

    Gordon, Evan M.

    2013-01-01

    Abstract We reviewed the extant literature with the goal of assessing the extent to which resting-state functional connectivity is associated with phenotypic variability in healthy and disordered populations. A large corpus of work has accumulated to date (125 studies), supporting the association between intrinsic functional connectivity and individual differences in a wide range of domains—not only in cognitive, perceptual, motoric, and linguistic performance, but also in behavioral traits (e.g., impulsiveness, risky decision making, personality, and empathy) and states (e.g., anxiety and psychiatric symptoms) that are distinguished by cognitive and affective functioning, and in neurological conditions with cognitive and motor sequelae. Further, intrinsic functional connectivity is sensitive to remote (e.g., early-life stress) and enduring (e.g., duration of symptoms) life experience, and it exhibits plasticity in response to recent experience (e.g., learning and adaptation) and pharmacological treatment. The most pervasive associations were observed with the default network; associations were also widespread between the cingulo-opercular network and both cognitive and affective behaviors, while the frontoparietal network was associated primarily with cognitive functions. Associations of somatomotor, frontotemporal, auditory, and amygdala networks were relatively restricted to the behaviors linked to their respective putative functions. Surprisingly, visual network associations went beyond visual function to include a variety of behavioral traits distinguished by affective function. Together, the reviewed evidence sets the stage for testing causal hypothesis about the functional role of intrinsic connectivity and augments its potential as a biomarker for healthy and disordered brain function. PMID:23294010

  18. Cancer Treatment-Related Cardiotoxicity: Understanding the Current State of Knowledge and Developing Future Research Priorities

    Cancer.gov

    Cancer Treatment-Related Cardiotoxicity: Understanding the Current State of Knowledge and Developing Future Research Priorities, a 2013 workshop sponsored by the Epidemiology and Genomics Research Program.

  19. Setting the Standard in Proteomics - Office of Cancer Clinical Proteomics Research

    Cancer.gov

    In a recently published article in the journal of Molecular and Cellular Proteomics, researchers outlined “best practices” for developing and publishing proteomic studies involving one of the field's signature state-of-the-art tools - targeted mass spectrometry (MS).

  20. The current state of scaffolds for musculoskeletal regenerative applications.

    PubMed

    Smith, Benjamin D; Grande, Daniel A

    2015-04-01

    Musculoskeletal disease and injury are highly prevalent conditions that lead to many surgical procedures. Autologous tissue transfer, allograft transplantation and nontissue prosthetics are currently used for the surgical treatment of critical-sized defects. However, the field of tissue engineering is actively investigating tissue-replacement solutions, many of which involve 3D scaffolds. Scaffolds must provide a balance of shape, biomechanical function and biocompatibility in order to achieve tissue replacement success. Different tissues can have different requirements for success, which has led to the development of various materials with unique characteristics. Articular cartilage scaffolds have the most robust clinical experience, with many scaffolds, mostly constructed of natural materials, showing promise, but levels of success vary. Tendon scaffolds also have proven clinical applications, with human-dermis-derived scaffolds showing the most potential. Synthetic and naturally derived meniscus scaffolds have been investigated in few clinical studies, but the results are encouraging. Bone scaffolds are limited to amorphous pastes and putties, owing to difficulties achieving adequate vascularization and biomechanical optimization. The complex physiological function and vascular demands of skeletal muscle have limited the widespread clinical use of scaffolds for engineering this tissue. Continued progress in preclinical study, not only of scaffolds, but also of other facets of tissue engineering, should enable the successful translation of musculoskeletal tissue engineering solutions to the clinic. PMID:25776947

  1. Current state in the development of candidate therapeutic HPV vaccines.

    PubMed

    Yang, Andrew; Jeang, Jessica; Cheng, Kevin; Cheng, Ting; Yang, Benjamin; Wu, T-C; Hung, Chien-Fu

    2016-08-01

    The identification of human papillomavirus (HPV) as an etiological factor for HPV-associated malignancies creates the opportunity to control these cancers through vaccination. Currently, available preventive HPV vaccines have not yet demonstrated strong evidences for therapeutic effects against established HPV infections and lesions. Furthermore, HPV infections remain extremely common. Thus, there is urgent need for therapeutic vaccines to treat existing HPV infections and HPV-associated diseases. Therapeutic vaccines differ from preventive vaccines in that they are aimed at generating cell-mediated immunity rather than neutralizing antibodies. The HPV-encoded early proteins, especially oncoproteins E6 and E7, form ideal targets for therapeutic HPV vaccines since they are consistently expressed in HPV-associated malignancies and precancerous lesions, playing crucial roles in the generation and maintenance of HPV-associated disease. Our review will cover various therapeutic vaccines in development for the treatment of HPV-associated lesions and cancers. Furthermore, we review strategies to enhance vaccine efficacy and the latest clinical trials on therapeutic HPV vaccines. PMID:26901118

  2. Current state and novel approaches of antiplatelet therapy.

    PubMed

    Metharom, Pat; Berndt, Michael C; Baker, Ross I; Andrews, Robert K

    2015-06-01

    An unresolved problem with clinical use of antiplatelet therapy is that a significant number of individuals either still get thrombosis or run the risk of life-threatening bleeding. Antiplatelet drugs are widely used clinically, either chronically for people at risk of athero/thrombotic disease or to prevent thrombus formation during surgery. However, a subpopulation may be resistant to standard doses, while the platelet targets of these drugs are also critical for the normal hemostatic function of platelets. In this review, we will briefly examine current antiplatelet therapy and existing targets while focusing on new potential approaches for antiplatelet therapy and improved monitoring of effects on platelet reactivity in individuals, ultimately to improve antithrombosis with minimal bleeding. Primary platelet adhesion-signaling receptors, glycoprotein (GP)Ib-IX-V and GPVI, that bind von Willebrand factor/collagen and other prothrombotic factors are not targeted by drugs in clinical use, but they are of particular interest because of their key role in thrombus formation at pathological shear. PMID:25838432

  3. Small-molecule PSMA ligands. Current state, SAR and perspectives.

    PubMed

    Machulkin, Alexey E; Ivanenkov, Yan A; Aladinskaya, Anastasia V; Veselov, Mark S; Aladinskiy, Vladimir A; Beloglazkina, Elena K; Koteliansky, Victor E; Shakhbazyan, Artem G; Sandulenko, Yuri B; Majouga, Alexander G

    2016-09-01

    Prostate cancer (PC) is the prevalent malignancy widespread among men in the Western World. Prostate specific membrane antigen (PSMA) is an established PC marker and has been considered as a promising biological target for anti-PC drug delivery and diagnostics. The protein was found to be overexpressed in PC cells, including metastatic, and the neovasculature of solid tumors. These properties make PSMA-based approach quite appropriate for effective PC imaging and specific drug therapy. Through the past decade, a variety of PSMA-targeted agents has been systematically evaluated. Small-molecule compounds have several advantages over other classes, such as improved pharmacokinetics and rapid blood clearance. These low-weight ligands have similar structure and can be divided into three basic categories in accordance with the type of their zinc-binding core-head. Several PSMA binders are currently undergoing clinical trials generally for PC imaging. The main goal of the present review is to describe the recent progress achieved within the title field and structure activity relationships (SAR) disclosed for different PSMA ligands. Recent in vitro and in vivo studies for each type of the compounds described have also been briefly summarized. PMID:26887438

  4. The state of sleep and the current brain paradigm

    PubMed Central

    Pigarev, Ivan N.; Pigareva, Marina L.

    2015-01-01

    Up to the present time cerebral cortex was considered as substrate for realization of the highest psychical functions including consciousness. Cortical sensory areas were regarded as structures specialized for processing of information coming from one particular modality (visual, auditory, somatosensory, and so on). However, studies of cortical activity in sleep-wake cycle demonstrated that during sleep the same neurons in the same cortical areas switch to processing of signals coming from the various visceral systems. After awakening these visceral responses disappear and the neurons return to processing of the information coming from the exteroreceptors. These observations indicate that most likely cortical areas are universal processors, which perform particular operations with incoming information independent of its origin. During wakefulness, results of the information processing on the cortical level should be directed to structures connected with organization of behavior and consciousness, while during sleep cortical outputs should be redirected to structures performing integration of the visceral information. Thus, results of sleep studies indicate that current brain paradigm should be changed. PMID:26528146

  5. A prospective look at the current state of open abdomens.

    PubMed

    Teixeira, Pedro G R; Salim, Ali; Inaba, Kenji; Brown, Carlos; Browder, Timothy; Margulies, Daniel; Demetriades, Demetrios

    2008-10-01

    The present study examines the current management, closure rate, and complications of open abdomens in trauma patients admitted to an Academic Level I trauma center between May 2004 and April 2007. Variables examined include mechanism, injuries, use of antibiotics and paralytics, type of abdominal closure, days to closure, complications, ICU and hospital length of stay, and mortality. Stepwise logistic regression was performed to identify independent predictors of failed abdominal closure. Of 900 laparotomies, 93 (10%) were left open. Eighty-five (91%) patients survived for closure opportunity. Definitive fascial closure was achieved in 72 (85%) at 3.9 +/- 3.7 days (range 1-21 days). Of the remaining 13 patients, seven were closed with biologic material, five by skin grafting, and one had skin-only closure. Entero-atmospheric fistulas occurred in 14 (15%) patients. Two independent risk factors associated with failed abdominal closure were the presence of deep surgical site infection [odds ratio (OR) 17.4; 95% confidence interval (CI) 2.6-115.8, P = 0.003] and intra-abdominal abscess (OR 7.4; 95% CI 1.1-51.0, P = 0.04). In conclusion, open abdomens are commonly necessary after trauma laparotomies. Definitive fascial closure can be achieved in 85 per cent of cases. In conjunction with biologics, closure can be achieved in 93 per cent of cases. Failure to primarily close the abdomen is associated with a significantly higher risk for entero-atmospheric fistula occurrence. PMID:18942608

  6. Current HDTV overview in the United States, Japan, and Europe

    NASA Astrophysics Data System (ADS)

    Cripps, Dale E.

    1991-08-01

    Vast resources are being spent on three continents, preparing for the commercialization of HDTV. The forces that together will launch this new industry are moving at dizzying speeds. This paper covers the highlights of events past and present and offers some predictions for the future. Difficult standards problems that keep brakes on the industry, and that will continue for some time to come. Standards committees have been set up around the world and are hard at work. It is a job with considerable technical and political challenges. By the time major plans and resources come together for commercialization of HDTV, one can trust that there will be adequately stable standards. But to observe the current status is to see a mess. High definition is not only consumer television. Because of its versatility, it is much more likely to find its way first into areas offering high returns such as medicine, education, printing, corporate communications, military and space, and even criminal control. HDTV is very likely to deliver movies and cultural events to theaters, and may also become the platform for a new generation of computers.

  7. Guide to clinical practice guidelines: the current state of play

    PubMed Central

    Kredo, Tamara; Bernhardsson, Susanne; Machingaidze, Shingai; Young, Taryn; Louw, Quinette; Ochodo, Eleanor; Grimmer, Karen

    2016-01-01

    Introduction Extensive research has been undertaken over the last 30 years on the methods underpinning clinical practice guidelines (CPGs), including their development, updating, reporting, tailoring for specific purposes, implementation and evaluation. This has resulted in an increasing number of terms, tools and acronyms. Over time, CPGs have shifted from opinion-based to evidence-informed, including increasingly sophisticated methodologies and implementation strategies, and thus keeping abreast of evolution in this field of research can be challenging. Methods This article collates findings from an extensive document search, to provide a guide describing standards, methods and systems reported in the current CPG methodology and implementation literature. This guide is targeted at those working in health care quality and safety and responsible for either commissioning, researching or delivering health care. It is presented in a way that can be updated as the field expands. Conclusion CPG development and implementation have attracted the most international interest and activity, whilst CPG updating, adopting (with or without contextualization), adapting and impact evaluation are less well addressed. PMID:26796486

  8. Current state of web accessibility of Malaysian ministries websites

    NASA Astrophysics Data System (ADS)

    Ahmi, Aidi; Mohamad, Rosli

    2016-08-01

    Despite the fact that Malaysian public institutions have progressed considerably on website and portal usage, web accessibility has been reported as one of the issues deserves special attention. Consistent with the government moves to promote an effective use of web and portal, it is essential for the government institutions to ensure compliance with established standards and guidelines on web accessibility. This paper evaluates accessibility of 25 Malaysian ministries websites using automated tools i.e. WAVE and Achecker. Both tools are designed to objectively evaluate web accessibility in conformance with Web Content Accessibility Guidelines 2.0 (WCAG 2.0) and United States Rehabilitation Act 1973 (Section 508). The findings reported somewhat low compliance to web accessibility standard amongst the ministries. Further enhancement is needed in the aspect of input elements such as label and checkbox to be associated with text as well as image-related elements. This findings could be used as a mechanism for webmasters to locate and rectify errors pertaining to the web accessibility and to ensure equal access of the web information and services to all citizen.

  9. The current state, challenges and perspectives of MR-PET.

    PubMed

    Herzog, Hans; Pietrzyk, Uwe; Shah, N Jon; Ziemons, Karl

    2010-02-01

    Following the success of PET/CT during the last decade and the recent increasing proliferation of SPECT/CT, another hybrid imaging instrument has been gaining more and more interest: MR-PET. First combined, simultaneous PET and MR studies carried out in small animals demonstrated the feasibility of the new approach. Concurrently, some prototypes of an MR-PET scanner for simultaneous human brain studies have been built, their performance is being tested and preliminary applications have already been shown. Through this pioneering work, it has become clear that advances in the detector design are necessary for further optimization. Recently, the different issues related to the present state and future prospects of MR-PET were presented and discussed during an international 2-day workshop at the Forschungszentrum Jülich, Germany, held after, and in conjunction with, the 2008 IEEE Nuclear Science Symposium and Medical Imaging Conference in Dresden, Germany on October 27-28, 2008. The topics ranged from small animal MR-PET imaging to human MR-BrainPET imaging, new detector developments, challenges/opportunities for ultra-high field MR-PET imaging and considerations of possible future research and clinical applications. This report presents a critical summary of the contributions made to the workshop. PMID:19853045

  10. Aggression in wild house mice: current state of affairs.

    PubMed

    Sluyter, F; van Oortmerssen, G A; de Ruiter, A J; Koolhaas, J M

    1996-09-01

    This paper reviews our present state of knowledge of genetic variation in (offensive) aggression in wild house mice. The basic tools in this research were lines bidirectionally selected for attack latency (fast attacking SAL and slow attacking LAL males), descended from a feral population. Using congenic lines for the nonpseudoautosomal region of the Y chromosome (YNPAR), reciprocal crosses between (parental) SAL and LAL, and crosses between parentals and congenics, an autosomally dependent Y chromosomal effect on aggression has been found. Both the pseudoautosomal (YPAK) region and the YNPAR play a role. As for environmental sources of variation, prenatal and postnatal maternal effects are of minor importance for the development of aggression differences. One of the physiological factors by which genetic effects may be mediated is testosterone (T). Besides quantitative aspects, the timing of T release seems crucial. Two important time frames are discussed: the perinatal and pubertal time periods. Finally, neurochemical and neuroanatomical correlates are considered. Differences in neostriatal dopaminergic activity, and sizes of the intra- and infrapyramidal mossy fiber terminal fields, as well as Y chromosomal effects on the latter two, are discussed. PMID:8917947

  11. Yeast as a cell factory: current state and perspectives.

    PubMed

    Kavšček, Martin; Stražar, Martin; Curk, Tomaž; Natter, Klaus; Petrovič, Uroš

    2015-01-01

    The yeast Saccharomyces cerevisiae is one of the oldest and most frequently used microorganisms in biotechnology with successful applications in the production of both bulk and fine chemicals. Yet, yeast researchers are faced with the challenge to further its transition from the old workhorse to a modern cell factory, fulfilling the requirements for next generation bioprocesses. Many of the principles and tools that are applied for this development originate from the field of synthetic biology and the engineered strains will indeed be synthetic organisms. We provide an overview of the most important aspects of this transition and highlight achievements in recent years as well as trends in which yeast currently lags behind. These aspects include: the enhancement of the substrate spectrum of yeast, with the focus on the efficient utilization of renewable feedstocks, the enhancement of the product spectrum through generation of independent circuits for the maintenance of redox balances and biosynthesis of common carbon building blocks, the requirement for accurate pathway control with improved genome editing and through orthogonal promoters, and improvement of the tolerance of yeast for specific stress conditions. The causative genetic elements for the required traits of the future yeast cell factories will be assembled into genetic modules for fast transfer between strains. These developments will benefit from progress in bio-computational methods, which allow for the integration of different kinds of data sets and algorithms, and from rapid advancement in genome editing, which will enable multiplexed targeted integration of whole heterologous pathways. The overall goal will be to provide a collection of modules and circuits that work independently and can be combined at will, depending on the individual conditions, and will result in an optimal synthetic host for a given production process. PMID:26122609

  12. Current state of development of the European Drought Observatory

    NASA Astrophysics Data System (ADS)

    Niemeyer, S.; de Jager, A.; Kurnik, B.; Laguardia, G.; Magni, D.; Nitcheva, O.; Rossi, S.; Weissteiner, C.

    2009-04-01

    The Joint Research Centre of the European Commission (JRC) is developing the prototype of the European Drought Observatory (EDO) for drought forecasting, detection, and monitoring in Europe. EDO is conceived as a web-based information system (http://edo.jrc.ec.europa.eu), integrating information from various sources and disciplines relevant to monitor and detect droughts throughout Europe. The prototype is currently performing the pre-operational production of drought indices using meteorological information, modelled hydrological parameters, and remote sensing data. In particular, the Standardized Precipitation Index (SPI) shows the general precipitation status according to the historical average in the predefined period. SPI in monthly step is calculated for the 1, 3, 6, 9 and 12 months averaging periods. Soil moisture estimations are produced daily by the LISFLOOD hydrological model, along with their anomalies and seven days forecasts. Two satellite remote sensing drought indicators are produced: Normalized Difference Water Index (NDWI) and Fraction of Absorbed Photosynthetic Active Radiation (fAPAR) anomalies. NDWI 10-day composites are obtained daily from Moderate Resolution Imaging Spectroradiometer (MODIS) data, while fAPAR anomalies are calculated from 10-day composites delivered by the European Space Agency (ESA) and estimated from Medium Resolution Imaging Spectrometer Instrument (MERIS) data. All these drought indicators are made available online for visualization and querying by means of a map viewer based on University of Minnesota MapServer and Oracle. The tool generates maps of the different indicators and provides functionalities to browse the maps, query the data, produce graphs, and output the maps in various formats.

  13. Circulating vaccine-derived polioviruses: current state of knowledge.

    PubMed Central

    Kew, Olen M.; Wright, Peter F.; Agol, Vadim I.; Delpeyroux, Francis; Shimizu, Hiroyuki; Nathanson, Neal; Pallansch, Mark A.

    2004-01-01

    Within the past 4 years, poliomyelitis outbreaks associated with circulating vaccine-derived polioviruses (cVDPVs) have occurred in Hispaniola (2000-01), the Philippines (2001), and Madagascar (2001-02). Retrospective studies have also detected the circulation of endemic cVDPV in Egypt (1988-93) and the likely localized spread of oral poliovirus vaccine (OPV)-derived virus in Belarus (1965-66). Gaps in OPV coverage and the previous eradication of the corresponding serotype of indigenous wild poliovirus were the critical risk factors for all cVDPV outbreaks. The cVDPV outbreaks were stopped by mass immunization campaigns using OPV. To increase sensitivity for detecting vaccine-derived polioviruses (VDPVs), in 2001 the Global Polio Laboratory Network implemented additional testing requirements for all poliovirus isolates under investigation. This approach quickly led to the recognition of the Philippines and Madagascar cVDPV outbreaks, but of no other current outbreaks. The potential risk of cVDPV emergence has increased dramatically in recent years as wild poliovirus circulation has ceased in most of the world. The risk appears highest for the type 2 OPV strain because of its greater tendency to spread to contacts. The emergence of cVDPVs underscores the critical importance of eliminating the last pockets of wild poliovirus circulation, maintaining universally high levels of polio vaccine coverage, stopping OPV use as soon as it is safely possible to do so, and continuing sensitive poliovirus surveillance into the foreseeable future. Particular attention must be given to areas where the risks for wild poliovirus circulation have been highest, and where the highest rates of polio vaccine coverage must be maintained to suppress cVDPV emergence. PMID:15106296

  14. Current state of the art of medical foods.

    PubMed

    Blum, Stephanie; Brito, Fernando

    2014-01-01

    Inflammatory bowel disease (IBD) is one of the five most prevalent gastrointestinal disease burdens in the US, with an overall health care cost of more than USD 1.7 billion. It commonly requires a lifetime of care, and accounts for more than 700,000 physician visits, 100,000 hospitalizations, and disability in 119,000 patients each year. IBD is a multifactorial disease and comprises genetic susceptibility, uncontrolled immune responses, and environmental factors which play a role in the pathogenesis and course of the disease. IBD patients are lifelong on medication, either for induction or maintenance therapy. Current treatment option (corticosteroids, immune suppressants, biologics), administered in mono- or combination therapy, are still unsatisfactory. Due to the nature of disease, 20-40% of patients relapse within the first 12 months. Although modern treatment algorithms have diminished the risk of surgery, the treatments harbor significant side effects, which impacts patients' quality of life. The role of nutrition in IBD has gathered high interest, especially in pediatric Crohn's disease, where studies have shown that exclusive enteral nutrition can induce remission in mild-to-moderate disease comparable to corticosteroids. Thus, gastroenterologists and patients become increasingly aware that specific nutritional interventions offered in addition to the standard of care are an appealing option for a safe long-term disease management. Such specific nutritional solutions should be based on scientific/clinical evidence and specifically designed to address the patients' distinct nutritional requirements. As per definition, these nutrition products fall under the regulatory framework of a Medical Food (Foods for Special Medical Purposes in Europe). PMID:25227302

  15. Current cigarette smoking among adults - United States, 2005-2014.

    PubMed

    Jamal, Ahmed; Homa, David M; O'Connor, Erin; Babb, Stephen D; Caraballo, Ralph S; Singh, Tushar; Hu, S Sean; King, Brian A

    2015-11-13

    Tobacco smoking is the leading cause of preventable disease and death in the United States, resulting in approximately 480,000 premature deaths and more than $300 billion in direct health care expenditures and productivity losses each year (1). To assess progress toward achieving the Healthy People 2020 objective of reducing the percentage of U.S. adults who smoke cigarettes to ≤12.0%,* CDC assessed the most recent national estimates of smoking prevalence among adults aged ≥18 years using data from the 2014 National Health Interview Survey (NHIS). The percentage of U.S. adults who smoke cigarettes declined from 20.9% in 2005 to 16.8% in 2014. Among daily cigarette smokers, declines were observed in the percentage who smoked 20–29 cigarettes per day (from 34.9% to 27.4%) or ≥30 cigarettes per day (from 12.7% to 6.9%). In 2014, prevalence of cigarette smoking was higher among males, adults aged 25–44 years, multiracial persons and American Indian/Alaska Natives, persons who have a General Education Development certificate, live below the federal poverty level, live in the Midwest, are insured through Medicaid or are uninsured, have a disability or limitation, or are lesbian, gay, or bisexual. Proven population-based interventions, including tobacco price increases, comprehensive smoke-free laws, high impact mass media campaigns, and barrier-free access to quitting assistance, are critical to reduce cigarette smoking and smoking-related disease and death among U.S. adults. PMID:26562061

  16. United States refugee and asylum policy: history and current approaches.

    PubMed

    Stein, B N

    1986-01-01

    For most of the 4 decades since World War II, US refugee and asylum policy has been generous but ad hoc, discretionary, and highly variable favoring some refugee groups and discriminating against or ignoring others. This paper: 1) tries to clarify some of the terminology of the refugee field and explains the distinctions between asylum and resettlement, 2) provides some of the historical background that has brought the US to its present condition and chronicles the US overseas refugee admission policy, and 3) examines some asylum issues and other refugee issues. Asylum is far more difficult to control than refugee resettlement. As a result of what is perceived to be abuse of the asylum system, the US has joined the growing tendency of states to treat asylum-seekers as illegal migrants. The greatest problem with American asylum policy is its lack of fairness of application; many critics believe that foreign policy factors dominate asylum hearings rather than the individual merits of the case. The 3 classic solutions to this problem are resettlement, voluntary repatriation, and settlement in a country of 1st asylum. Only in the Indochinese refugee crisis has resettlement been widely used as a solution for 3rd World refugees. Nationalism and nation-building conflicts are at the root of many refugee movements; hosts are often no less nationalistic than source countries, thus many non-integrated refugees live in peril. Developed country political will and statesmanship are needed to revive resettlement as a durable solution. Resettlement may be difficult and costly, but the pluralistic western societies do offer an integrated new life. PMID:12178938

  17. Current State of the Art in High Brightness LEDs

    NASA Astrophysics Data System (ADS)

    Craford, George

    2007-03-01

    LED's have been commercially available since the 1960's. For many years they were used primarily for indicator applications. The remarkable increase in materials technology and efficiency that has been achieved since the early 1990's for AlInGaP red and amber LEDs, and InGaN green and blue LEDs, has enabled the penetration of markets such as outdoor display, signaling, and automotive brake light and turn signal applications. White LEDs, which are either blue LEDs combined with a phosphor, or a combination of red, green, and blue LEDs, are being used in emerging applications such as cell phone flash, television backlights, projection, and automotive headlights. In addition, to efficiency improvements these applications have required the development of higher power packages and, in some of these applications which are etendue limited, higher luminance devices. High power devices are commercially available which are capable of 140 lumens output and have an efficacy of around 70 lm/W for white emission. New package and chip technologies have been demonstrated which have a luminance of 38 mega nits (Mcd/m^2), approximately 50% more luminance than that of an automotive headlamp halogen bulb (˜25 mega nits). The recent progress in materials technology, packaging, and chip technology makes it clear that LED's will become important for general illumination applications. The rate of LED penetration of this market will depend upon continued increases in performance and lower costs as well as better control of the white spectral emission. Efficiency, current density, and costs are closely linked because the cost in dollars/lumen is inversely proportional to how many lumens can be realized from each unit of device area for a given device type. Performance as high as 138 lm/W, and over 40% wall plug efficiency, has been reported for low power research devices and over 90 lm/W for high power research devices. It is clear that high power commercial products with performance in

  18. The current state of seismic monitoring in Switzerland

    NASA Astrophysics Data System (ADS)

    Clinton, J. F.; Haslinger, F.; Diehl, T.; Cauzzi, C.; Plenkers, K.; Kästli, P.; Fäh, D.; Wiemer, S.

    2013-12-01

    The Swiss Seismological Service at ETH Zurich (SED) operates both the national strong motion and broadband permanent seismic networks in Switzerland, as well as supporting local real-time densifications related to projects (such as geothermal explorations and major tunneling) and a mobile pool for national and international deployments related to research and aftershock studies. This submission provides an overview of the current status of network monitoring in Switzerland. A digital high gain network has been operating since 1974 and was upgraded to a continuously recording realtime modern 24 bit broadband network comprising 30 stations from 1999-2002, with station spacing averaging ~30km across the nation. Various improvements and densifications since then have raised the number of broadband sensors to 45 and added co-located strong motion sensors at 13 sites. A notable recent densification is in the NE of Switzerland, where the Swiss National Cooperative for the Disposal of Radioactive Waste (Nagra) have funded an additional 10 broadband stations (including 3 100-200m deep borehole short period stations) in order to reduce the earthquake detection threshold and increase location accuracy in regions that are identified as potential deep nuclear waste storage sites. A strong motion network has been maintained since 1990, comprising 70 12-16 bit triggered sensors located predominantly in free-field urban sites but also including arrays on dams. The free-field network is in the midst of an upgrade (2009-2018), with 30 new stations already installed from the eventual 100 new free-field 24-bit real-time continuous stations. A project has just begun to upgrade the Swiss broadband network, which will co-locate strong-motion sensors at existing broadband sites; assess and implement improvements of installation quality, e.g. by shallow post-hole installations rather than surface vaults; and potentially fill remaining gaps in station coverage. The seismic network has

  19. Biological therapies in the spondyloarthritides--the current state.

    PubMed

    Braun, J; Sieper, J

    2004-09-01

    Therapeutic options for patients suffering from the more severe spondyloarthritides (SpA) have been rather limited in the last decades. Evidence is now accumulating that anti-tumour necrosis factor (TNF) therapy is highly effective in SpA, especially in ankylosing spondylitis (AS) and psoriatic arthritis (PsA). Based on the data recently published concerning more than 1000 patients with AS and PsA, this treatment seems to be even more effective than in rheumatoid arthritis (RA). The anti-TNFalpha agents currently available, infliximab (Remicade), etanercept (Enbrel) and adalimumab (Humira), are approved for the treatment of RA in the USA and Europe. The situation for SpA is different from RA because there is an unmet medical need, especially in AS, since no therapies with disease-modifying anti-rheumatic drugs (DMARDs) are available for severely affected patients, especially those with spinal disease. Thus, TNF blockers may even be considered a first-line treatment in a patient with active AS and PsA whose condition is not sufficiently controlled with non-steroidal anti-inflammatory drugs (NSAIDs) in the case of axial disease, and sulphasalazine or methotrexate in the case of peripheral arthritis. For infliximab, a dose of 5 mg/kg is required, and intervals of between 6 and 12 weeks are necessary to constantly suppress disease activity-also a major aim for long-term treatment. The standard dosage of etanercept is 2 x 25 mg subcutaneously per week. There are almost no studies yet on adalimumab (standard dose in RA, 20-40 mg subcutaneously every 1-2 weeks) in SpA. Infliximab and etanercept are now both approved for AS in Europe. The efficacy of etanercept was first demonstrated in PsA, and it is now approved for this indication in the USA and Europe. There is preliminary evidence that both agents also work in other SpA, such as undifferentiated SpA (uSpA). Studies should be performed to document the long-term efficacy of this treatment. There is hope that ankylosis

  20. [Malaria in Hungary: origin, current state and principles of prevention].

    PubMed

    Szénási, Zsuzsanna; Vass, Adám; Melles, Márta; Kucsera, István; Danka, József; Csohán, Agnes; Krisztalovics, Katalin

    2003-05-25

    Malaria was an endemic disease in Hungary for many centuries. A country-wide survey of the epidemiologic situation on malaria started in the year of 1927. That was done by the Department of Parasitology of the Royal State Institute of Hygiene (presently: Johan Béla National Center for Epidemiology). The notification of malaria was made compulsory in 1930. Free of charge laboratory examination of the blood of persons suffering from malaria or suspected of an infection have been carried out. Anti-malarial drugs were also distributed free of charge, together with appropriate medical advise given at the anti-malarial sanitary stations. Between 1933 and 1943, the actual number of malaria cases was estimated as high as 10-100,000 per year. The major breakthrough came in 1949 by the organized antimalarial campaign applying DDT for mosquito eradication. The drastic reduction of the vectors resulted in the rapid decline of malaria cases. Since 1956, there have not been reported any indigenous case in Hungary. In 1963, Hungary entered on the Official Register of the WHO to the areas where malaria eradication has been achieved. During the period of 1963-2001, 169 Hungarians acquired the malaria in abroad and 263 foreigners infected in abroad were registered in Hungary. More than half of the cases (230) were caused by Plasmodium falciparum. Further 178 cases were caused by Plasmodium vivax and 24 cases by other Plasmodium species. During that period, 7 fatal cases were reported (Plasmodium falciparum). The expansion of migration (both the increase of the number of foreigners travelling into Hungary and of Hungarians travelling abroad) favours to the appearance of imported cases. Attention is called of all the persons travelling to malaria endemic countries to the importance of malaria prevention by the International Vaccination Stations located in the National Center for Epidemiology and in the Public Health Institutes of 19 counties and of Budapest. The Johan Béla National

  1. 78 FR 9929 - Current Traumatic Brain Injury State Implementation Partnership Grantees; Non-Competitive One...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-02-12

    ... HUMAN SERVICES Health Resources and Services Administration Current Traumatic Brain Injury State... Services Administration (HRSA), Department of Health and Human Services (HHS). ACTION: Notice of Non-Competitive One-Year Extension Funds for Current Traumatic Brain Injury (TBI) State Implementation...

  2. 75 FR 7284 - NIOSH Current Intelligence Bulletin-Asbestos Fibers and Other Elongate Mineral Particles: State...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-02-18

    ... HUMAN SERVICES Centers for Disease Control and Prevention NIOSH Current Intelligence Bulletin--Asbestos... available for public comment entitled ``NIOSH Current Intelligence Bulletin--Asbestos Fibers and Other..., ``NIOSH Current Intelligence Bulletin--Asbestos Fibers and Other Elongate Mineral Particles: State of...

  3. Current Control in ITER Steady State Plasmas With Neutral Beam Steering

    SciTech Connect

    R.V. Budny

    2009-09-10

    Predictions of quasi steady state DT plasmas in ITER are generated using the PTRANSP code. The plasma temperatures, densities, boundary shape, and total current (9 - 10 MA) anticipated for ITER steady state plasmas are specified. Current drive by negative ion neutral beam injection, lower-hybrid, and electron cyclotron resonance are calculated. Four modes of operation with different combinations of current drive are studied. For each mode, scans with the NNBI aimed at differing heights in the plasma are performed to study effects of current control on the q profile. The timeevolution of the currents and q are calculated to evaluate long duration transients. Quasi steady state, strongly reversed q profiles are predicted for some beam injection angles if the current drive and bootstrap currents are sufficiently large.

  4. Proteomics Analysis of the Causative Agent of Typhoid Fever

    SciTech Connect

    Ansong, Charles; Yoon, Hyunjin; Norbeck, Angela D.; Gustin, Jean K.; McDermott, Jason E.; Mottaz, Heather M.; Rue, Joanne; Adkins, Joshua N.; Heffron, Fred; Smith, Richard D.

    2008-02-01

    Typhoid fever is a potentially fatal disease caused by the bacterial pathogen Salmonella enterica serovar Typhi (S. typhi). S. typhi infection is a complex process that involves numerous bacterially-encoded virulence determinants, and these are thought to confer both stringent human host specificity and a high mortality rate. In the present study we used a liquid chromatography-mass spectrometry (LC-MS) based proteomics strategy to investigate the proteome of logarithmic, stationary phase, and low pH/low magnesium (MgM) S. typhi cultures. This represents the first large scale comprehensive characterization of the S. typhi proteome. Our analysis identified a total of 2066 S. typhi proteins. In an effort to identify putative S. typhi-specific virulence factors, we then compared our S. typhi results to those obtained in a previously published study of the S. typhimurium proteome under similar conditions (Adkins J.N. et al (2006) Mol Cell Prot). Comparative proteomic analysis of S. typhi (strain Ty2) and S. typhimurium (strains LT2 and 14028) revealed a subset of highly expressed proteins unique to S. typhi that were exclusively detected under conditions that mimic the infective state in macrophage cells. These proteins included CdtB, HlyE, and a conserved protein encoded by t1476. The differential expression of selected proteins was confirmed by Western blot analysis. Taken together with the current literature, our observations suggest that this subset of proteins may play a role in S. typhi pathogenesis and human host specificity. In addition, we observed products of the biotin (bio) operon displayed a higher abundance in the more virulent strains S. typhi-Ty2 and S. typhimurium-14028 compared to the virulence attenuated S. typhimurium strain LT2, suggesting bio proteins may contribute to Salmonella pathogenesis.

  5. Selective equilibration among the current-carrying states in the quantum Hall regime

    NASA Technical Reports Server (NTRS)

    Alphenaar, B. W.; Mceuen, P. L.; Wheeler, R. G.; Sacks, R. N.

    1990-01-01

    The Hall resistance of a two-dimensional electron gas is measured with gated probes to determine the extent of equilibration among the N current-carrying states in the quantum Hall regime. After traveling macroscopic distances, current injected into the first state is equilibrated among the N - 1 lowest states but equilibration into the highest state varies strongly across the Hall plateau. This is attributed to a change in the Nth state from being localized within a magnetic length of the edge to substantially extending into the sample.

  6. Polyploidy and the proteome.

    PubMed

    Soltis, Douglas E; Misra, Biswapriya B; Shan, Shengchen; Chen, Sixue; Soltis, Pamela S

    2016-08-01

    Although major advances have been made during the past 20 years in our understanding of the genetic and genomic consequences of polyploidy, our knowledge of polyploidy and the proteome is in its infancy. One of our goals is to stimulate additional study, particularly broad-scale proteomic analyses of polyploids and their progenitors. Although it may be too early to generalize regarding the extent to which transcriptomic data are predictive of the proteome of polyploids, it is clear that the proteome does not always reflect the transcriptome. Despite limited data, important observations on the proteomes of polyploids are emerging. In some cases, proteomic profiles show qualitatively and/or quantitatively non-additive patterns, and proteomic novelty has been observed. Allopolyploids generally combine the parental contributions, but there is evidence of parental dominance of one contributing genome in some allopolyploids. Autopolyploids are typically qualitatively identical to but quantitatively different from their parents. There is also evidence of parental legacy at the proteomic level. Proteomes clearly provide insights into the consequences of genomic merger and doubling beyond what is obtained from genomic and/or transcriptomic data. Translating proteomic changes in polyploids to differences in morphology and physiology remains the holy grail of polyploidy--this daunting task of linking genotype to proteome to phenotype should emerge as a focus of polyploidy research in the next decade. This article is part of a Special Issue entitled: Plant Proteomics--a bridge between fundamental processes and crop production, edited by Dr. Hans-Peter Mock. PMID:26993527

  7. 42 CFR 457.80 - Current State child health insurance coverage and coordination.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 42 Public Health 4 2012-10-01 2012-10-01 false Current State child health insurance coverage and coordination. 457.80 Section 457.80 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) STATE CHILDREN'S HEALTH INSURANCE PROGRAMS (SCHIPs) ALLOTMENTS AND GRANTS TO STATES Introduction;...

  8. 42 CFR 457.80 - Current State child health insurance coverage and coordination.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 42 Public Health 4 2014-10-01 2014-10-01 false Current State child health insurance coverage and coordination. 457.80 Section 457.80 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) STATE CHILDREN'S HEALTH INSURANCE PROGRAMS (SCHIPs) ALLOTMENTS AND GRANTS TO STATES Introduction;...

  9. 42 CFR 457.80 - Current State child health insurance coverage and coordination.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 42 Public Health 4 2013-10-01 2013-10-01 false Current State child health insurance coverage and coordination. 457.80 Section 457.80 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) STATE CHILDREN'S HEALTH INSURANCE PROGRAMS (SCHIPs) ALLOTMENTS AND GRANTS TO STATES Introduction;...

  10. 42 CFR 457.80 - Current State child health insurance coverage and coordination.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 42 Public Health 4 2011-10-01 2011-10-01 false Current State child health insurance coverage and coordination. 457.80 Section 457.80 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) STATE CHILDREN'S HEALTH INSURANCE PROGRAMS (SCHIPs) ALLOTMENTS AND GRANTS TO STATES Introduction;...

  11. Expanding the mouse embryonic stem cell proteome: Combining three proteomic approaches

    PubMed Central

    Gundry, Rebekah L.; Tchernyshyov, Irina; Sheng, Shijun; Tarasova, Yelena; Raginski, Kimberly; Boheler, Kenneth R.; Van Eyk, Jennifer E.

    2010-01-01

    The current study used three different proteomic strategies, which differed by their extent of intact protein separation, to examine the proteome of a pluripotent mouse embryonic stem cell line, R1. Proteins from whole-cell lysates were subjected either to 2-D-LC, or 1-DE, or were unfractionated prior to enzymatic digestion and subsequent analysis by MS. The results yielded 1895 identified non-redundant proteins and, for 128 of these, the specific isoform could be determined based on detection of an isoform-specific peptide. When compared with two previously published proteomic studies that used the same cell line, the current study reveals 612 new proteins. PMID:20512790

  12. Steady-State Currents through Nanodevices: A Scattering-States Numerical Renormalization-Group Approach to Open Quantum Systems

    NASA Astrophysics Data System (ADS)

    Anders, Frithjof B.

    2008-08-01

    We propose a numerical renormalization group (NRG) approach to steady-state currents through nanodevices. A discretization of the scattering-states continuum ensures the correct boundary condition for an open quantum system. We introduce two degenerate Wilson chains for current carrying left- and right-moving electrons reflecting time-reversal symmetry in the absence of a finite bias V. We employ the time-dependent NRG to evolve the known steady-state density operator for a noninteracting junction into the density operator of the fully interacting nanodevice at finite bias. We calculate the differential conductance as function of V, T, and the external magnetic field.

  13. Identification of phosphoproteins associated with maintenance of transformed state in temperature-sensitive Rous sarcoma-virus infected cells by proteomic analysis

    SciTech Connect

    Yamaoka, Kazuko . E-mail: yamaoka@rinshoken.or.jp; Imajoh-Ohmi, Shinobu; Fukuda, Hiroyuki; Akita, Yoshiko; Kurosawa, Keiko; Yamamoto, Yukio; Sanai, Yutaka

    2006-07-07

    To identify phosphotyrosine-containing proteins essential for maintaining the transformed state, we studied the tyrosine phosphorylation profile of temperature-sensitive mutant of Rous sarcoma virus, tsNY68, infected cells (68N7). Shifting the temperature from 39 {sup o}C (nonpermissive) to 32 {sup o}C (permissive) markedly increased the expression of phosphotyrosine-containing cell membrane proteins of {approx}40 kDa, as assessed by SDS-PAGE. Membrane and nuclear proteins were separated by two-dimensional gel electrophoresis and immunoblotted with anti-phosphotyrosine antibody. Proteins showing temperature-dependent changes in phosphorylation profile were subjected to in-gel digestion with trypsin and analyzed by mass spectrometry. Five proteins were identified: heterogeneous nuclear ribonucleoprotein (hnRNP) A3, hnRNP A2, annexin II, phosphoglycerate mutase 1, and triosephosphate isomerase 1. hnRNP A3 was phosphorylated at serine residues and had both serine and tyrosine phosphorylated sites. These results suggest an important complementary role for proteomics in identifying molecular abnormalities associated with tumor progression that may be attractive candidates for tumor diagnosis.

  14. Proteomic Analysis of Chinese Hamster Ovary Cells

    PubMed Central

    Baycin-Hizal, Deniz; Tabb, David L.; Chaerkady, Raghothama; Chen, Lily; Lewis, Nathan E.; Nagarajan, Harish; Sarkaria, Vishaldeep; Kumar, Amit; Wolozny, Daniel; Colao, Joe; Jacobson, Elena; Tian, Yuan; O'Meally, Robert N.; Krag, Sharon S.; Cole, Robert N.; Palsson, Bernhard O.; Zhang, Hui; Betenbaugh, Michael

    2013-01-01

    In order to complement the recent genomic sequencing of Chinese hamster ovary (CHO) cells, proteomic analysis was performed on CHO including the cellular proteome, secretome, and glycoproteome using tandem mass spectrometry (MS/MS) of multiple fractions obtained from gel electrophoresis, multi-dimensional liquid chromatography, and solid phase extraction of glycopeptides (SPEG). From the 120 different mass spectrometry analyses generating 682,097 MS/MS spectra, 93,548 unique peptide sequences were identified with at most a 0.02 false discovery rate (FDR). A total of 6164 grouped proteins were identified from both glycoproteome and proteome analysis, representing an 8-fold increase in the number of proteins currently identified in the CHO proteome. Furthermore, this is the first proteomic study done using CHO genome exclusively which provides for more accurate identification of proteins. From this analysis, the CHO codon frequency was determined and found to be distinct from humans, which will facilitate expression of human proteins in CHO cells. Analysis of the combined proteomic and mRNA data sets indicated the enrichment of a number of pathways including protein processing and apoptosis but depletion of proteins involved in steroid hormone and glycosphingolipid metabolism. 504 of the detected proteins included N-acetylation modifications and 1292 different proteins were observed to be N-glycosylated. This first large-scale proteomic analysis will enhance the knowledge base about CHO capabilities for recombinant expression and provide information useful in cell engineering efforts aimed at modifying CHO cellular functions. PMID:22971049

  15. Proteomic analysis of Chinese hamster ovary cells.

    PubMed

    Baycin-Hizal, Deniz; Tabb, David L; Chaerkady, Raghothama; Chen, Lily; Lewis, Nathan E; Nagarajan, Harish; Sarkaria, Vishaldeep; Kumar, Amit; Wolozny, Daniel; Colao, Joe; Jacobson, Elena; Tian, Yuan; O'Meally, Robert N; Krag, Sharon S; Cole, Robert N; Palsson, Bernhard O; Zhang, Hui; Betenbaugh, Michael

    2012-11-01

    To complement the recent genomic sequencing of Chinese hamster ovary (CHO) cells, proteomic analysis was performed on CHO cells including the cellular proteome, secretome, and glycoproteome using tandem mass spectrometry (MS/MS) of multiple fractions obtained from gel electrophoresis, multidimensional liquid chromatography, and solid phase extraction of glycopeptides (SPEG). From the 120 different mass spectrometry analyses generating 682,097 MS/MS spectra, 93,548 unique peptide sequences were identified with at most 0.02 false discovery rate (FDR). A total of 6164 grouped proteins were identified from both glycoproteome and proteome analysis, representing an 8-fold increase in the number of proteins currently identified in the CHO proteome. Furthermore, this is the first proteomic study done using the CHO genome exclusively, which provides for more accurate identification of proteins. From this analysis, the CHO codon frequency was determined and found to be distinct from humans, which will facilitate expression of human proteins in CHO cells. Analysis of the combined proteomic and mRNA data sets indicated the enrichment of a number of pathways including protein processing and apoptosis but depletion of proteins involved in steroid hormone and glycosphingolipid metabolism. Five-hundred four of the detected proteins included N-acetylation modifications, and 1292 different proteins were observed to be N-glycosylated. This first large-scale proteomic analysis will enhance the knowledge base about CHO capabilities for recombinant expression and provide information useful in cell engineering efforts aimed at modifying CHO cellular functions. PMID:22971049

  16. Legume proteomics: Progress, prospects, and challenges.

    PubMed

    Rathi, Divya; Gayen, Dipak; Gayali, Saurabh; Chakraborty, Subhra; Chakraborty, Niranjan

    2016-01-01

    Legumes are the major sources of food and fodder with strong commercial relevance, and are essential components of agricultural ecosystems owing to their ability to carry out endosymbiotic nitrogen fixation. In recent years, legumes have become one of the major choices of plant research. The legume proteomics is currently represented by more than 100 reference maps and an equal number of stress-responsive proteomes. Among the 48 legumes in the protein databases, most proteomic studies have been accomplished in two model legumes, soybean, and barrel medic. This review highlights recent contributions in the field of legume proteomics to comprehend the defence and regulatory mechanisms during development and adaptation to climatic changes. Here, we attempted to provide a concise overview of the progress in legume proteomics and discuss future developments in three broad perspectives: (i) proteome of organs/tissues; (ii) subcellular compartments; and (iii) spatiotemporal changes in response to stress. Such data mining may aid in discovering potential biomarkers for plant growth, in general, apart from essential components involved in stress tolerance. The prospect of integrating proteome data with genome information from legumes will provide exciting opportunities for plant biologists to achieve long-term goals of crop improvement and sustainable agriculture. PMID:26563903

  17. Proteomic analysis of neurons microdissected from formalin-fixed, paraffin-embedded Alzheimer’s disease brain tissue

    PubMed Central

    Drummond, Eleanor S; Nayak, Shruti; Ueberheide, Beatrix; Wisniewski, Thomas

    2015-01-01

    The vast majority of human tissue specimens are formalin-fixed, paraffin embedded (FFPE) archival samples, making this type of tissue a potential gold mine for medical research. It is now accepted that proteomics can be done using FFPE tissue and can generate similar results as snap-frozen tissue. However, the current methodology requires a large amount of starting protein, limiting the questions that can be answered in these types of proteomics studies and making cell-type specific proteomics studies difficult. Cell-type specific proteomics has the potential to greatly enhance understanding of cell functioning in both normal and disease states. Therefore, here we describe a new method that allows localized proteomics on individual cell populations isolated from FFPE tissue sections using laser capture microdissection. To demonstrate this technique we microdissected neurons from archived tissue blocks of the temporal cortex from patients with Alzheimer’s disease. Using this method we identified over 400 proteins in microdissected neurons; on average 78% that were neuronal and 50% that were associated with Alzheimer’s disease. Therefore, this technique is able to provide accurate and meaningful data and has great potential for any future study that wishes to perform localized proteomics using very small amounts of archived FFPE tissue. PMID:26487484

  18. The Staphylococcus aureus proteome.

    PubMed

    Otto, Andreas; van Dijl, Jan Maarten; Hecker, Michael; Becher, Dörte

    2014-03-01

    Staphylococcus aureus is a Gram-positive commensal bacterium that is regarded as a major threat for modern health care systems. This relates both to the ability of S. aureus to overcome antibiotic therapy by developing high-level resistance against multiple antibiotics and this bacterium's extensive arsenal of virulence factors. Understanding the mechanisms of resistance and functional studies on stress and starvation responses are the main goals of proteomics in staphylococcal research. This review high-lights recent advances in gel-based and gel-free proteomics analyses of S. aureus and pinpoints the importance of location-specific proteomics studies targeting the cytosol, the membrane, the cell surface and the extracellular milieu in combination with integrated global proteome studies. Emerging hot topics in staphylococcal proteomics are discussed with special focus on in vivo proteomics, membrane vesicles, biofilm formation and the acquisition of absolute proteome data for systems biological modeling approaches. PMID:24439828

  19. Microfluidic integration for automated targeted proteomic assays.

    PubMed

    Hughes, Alex J; Lin, Robert K C; Peehl, Donna M; Herr, Amy E

    2012-04-17

    A dearth of protein isoform-based clinical diagnostics currently hinders advances in personalized medicine. A well-organized protein biomarker validation process that includes facile measurement of protein isoforms would accelerate development of effective protein-based diagnostics. Toward scalable protein isoform analysis, we introduce a microfluidic "single-channel, multistage" immunoblotting strategy. The multistep assay performs all immunoblotting steps: separation, immobilization of resolved proteins, antibody probing of immobilized proteins, and all interim wash steps. Programmable, low-dispersion electrophoretic transport obviates the need for pumps and valves. A three-dimensional bulk photoreactive hydrogel eliminates manual blotting. In addition to simplified operation and interfacing, directed electrophoretic transport through our 3D nanoporous reactive hydrogel yields superior performance over the state-of-the-art in enhanced capture efficiency (on par with membrane electroblotting) and sparing consumption of reagents (ca. 1 ng antibody), as supported by empirical and by scaling analyses. We apply our fully integrated microfluidic assay to protein measurements of endogenous prostate specific antigen isoforms in (i) minimally processed human prostate cancer cell lysate (1.1 pg limit of detection) and (ii) crude sera from metastatic prostate cancer patients. The single-instrument functionality establishes a scalable microfluidic framework for high-throughput targeted proteomics, as is relevant to personalized medicine through robust protein biomarker verification, systematic characterization of new antibody probes for functional proteomics, and, more broadly, to characterization of human biospecimen repositories. PMID:22474344

  20. Neural Stem Cells (NSCs) and Proteomics*

    PubMed Central

    Shoemaker, Lorelei D.; Kornblum, Harley I.

    2016-01-01

    Neural stem cells (NSCs) can self-renew and give rise to the major cell types of the CNS. Studies of NSCs include the investigation of primary, CNS-derived cells as well as animal and human embryonic stem cell (ESC)-derived and induced pluripotent stem cell (iPSC)-derived sources. NSCs provide a means with which to study normal neural development, neurodegeneration, and neurological disease and are clinically relevant sources for cellular repair to the damaged and diseased CNS. Proteomics studies of NSCs have the potential to delineate molecules and pathways critical for NSC biology and the means by which NSCs can participate in neural repair. In this review, we provide a background to NSC biology, including the means to obtain them and the caveats to these processes. We then focus on advances in the proteomic interrogation of NSCs. This includes the analysis of posttranslational modifications (PTMs); approaches to analyzing different proteomic compartments, such the secretome; as well as approaches to analyzing temporal differences in the proteome to elucidate mechanisms of differentiation. We also discuss some of the methods that will undoubtedly be useful in the investigation of NSCs but which have not yet been applied to the field. While many proteomics studies of NSCs have largely catalogued the proteome or posttranslational modifications of specific cellular states, without delving into specific functions, some have led to understandings of functional processes or identified markers that could not have been identified via other means. Many challenges remain in the field, including the precise identification and standardization of NSCs used for proteomic analyses, as well as how to translate fundamental proteomics studies to functional biology. The next level of investigation will require interdisciplinary approaches, combining the skills of those interested in the biochemistry of proteomics with those interested in modulating NSC function. PMID:26494823

  1. Neural Stem Cells (NSCs) and Proteomics.

    PubMed

    Shoemaker, Lorelei D; Kornblum, Harley I

    2016-02-01

    Neural stem cells (NSCs) can self-renew and give rise to the major cell types of the CNS. Studies of NSCs include the investigation of primary, CNS-derived cells as well as animal and human embryonic stem cell (ESC)-derived and induced pluripotent stem cell (iPSC)-derived sources. NSCs provide a means with which to study normal neural development, neurodegeneration, and neurological disease and are clinically relevant sources for cellular repair to the damaged and diseased CNS. Proteomics studies of NSCs have the potential to delineate molecules and pathways critical for NSC biology and the means by which NSCs can participate in neural repair. In this review, we provide a background to NSC biology, including the means to obtain them and the caveats to these processes. We then focus on advances in the proteomic interrogation of NSCs. This includes the analysis of posttranslational modifications (PTMs); approaches to analyzing different proteomic compartments, such the secretome; as well as approaches to analyzing temporal differences in the proteome to elucidate mechanisms of differentiation. We also discuss some of the methods that will undoubtedly be useful in the investigation of NSCs but which have not yet been applied to the field. While many proteomics studies of NSCs have largely catalogued the proteome or posttranslational modifications of specific cellular states, without delving into specific functions, some have led to understandings of functional processes or identified markers that could not have been identified via other means. Many challenges remain in the field, including the precise identification and standardization of NSCs used for proteomic analyses, as well as how to translate fundamental proteomics studies to functional biology. The next level of investigation will require interdisciplinary approaches, combining the skills of those interested in the biochemistry of proteomics with those interested in modulating NSC function. PMID:26494823

  2. The proteomics of pediatric brain tumors.

    PubMed

    Anagnostopoulos, Athanasios K; Tsangaris, George T

    2014-10-01

    Pediatric tumors of the CNS are the leading cause of cancer-related mortality in children. In pediatric pathology, brain tumors constitute the most frequent solid malignancy. An unparalleled outburst of information in pediatric neuro-oncology research has been witnessed over the last few years, largely due to increased use of high-throughput technologies such as genomics, proteomics and meta-analysis tools. Input from these technologies gives scientists the advantage of early prognosis assessment, more accurate diagnosis and prospective curative intent in the pediatric brain tumor clinical setting. The present review aims to summarize current knowledge on research applying proteomics techniques or proteomics-based approaches performed on pediatric brain tumors. Proteins that can be used as potential disease markers or molecular targets, and their biological significance, are herein listed and discussed. Furthermore, future perspectives that proteomics technologies may offer regarding this devastating disorder are presented. PMID:25059388

  3. Proteomic analysis of protein expression in the induction of the viable but Nonculturable State of Vibrio harveyi SF1.

    PubMed

    Jia, Juntao; Li, Zhengyi; Cao, Jijuan; Jiang, Yinghui; Liang, Chengzhu; Liu, Mengzhen

    2013-10-01

    Vibrio harveyi has been reported to enter into a viable but nonculturable (VBNC) state. One marine V. harveyi strain, SF1 became nonculturable when incubated in seawater microcosm at 4 °C within 60 days. We investigated protein expression in the exponential phase of V. harveyi SF1 and compared it to the VBNC state. Cytosolic proteins were resolved by two-dimensional polyacrylamide gel electrophoresis using pH 4-7 linear gradients. Among these proteins, sixteen proteins which were strongly downregulated or upregulated in the VBNC cells were identified by MALDI-TOF-TOF mass spectrometry. The results indicated that the differentially expressed proteins were mainly focused on stress response proteins and key components of central and intermediary metabolism, like carbohydrate metabolism, transport, and translation. This study provided clues for understanding the mechanism of adaptation to the VBNC state. PMID:23689940

  4. A perspective on proteomics in cell biology

    PubMed Central

    Ahmad, Yasmeen; Lamond, Angus I.

    2014-01-01

    During the past 15 years mass spectrometry (MS)-based analyses have become established as the method of choice for direct protein identification and measurement. Owing to the remarkable improvements in the sensitivity and resolution of MS instruments, this technology has revolutionised the opportunities available for the system-wide characterisation of proteins, with wide applications across virtually the whole of cell biology. In this article we provide a perspective on the current state of the art and discuss how the future of cell biology research may benefit from further developments and applications in the field of MS and proteomics, highlighting the major challenges ahead for the community in organising the effective sharing and integration of the resulting data mountain. PMID:24284280

  5. Assessment of Energy Production Potential from Ocean Currents along the United States Coastline

    SciTech Connect

    Haas, Kevin A.

    2013-10-03

    Increasing energy consumption and depleting reserves of fossil fuels have resulted in growing interest in alternative renewable energy from the ocean. Ocean currents are an alternative source of clean energy due to their inherent reliability, persistence and sustainability. General ocean circulations exist in the form of large rotating ocean gyres, and feature extremely rapid current flow in the western boundaries due to the Coriolis Effect. The Gulf Stream system is formed by the western boundary current of the North Atlantic Ocean that flows along the east coastline of the United States, and therefore is of particular interest as a potential energy resource for the United States.

  6. DNA sequence-dependent ionic currents in ultra-small solid-state nanopores

    NASA Astrophysics Data System (ADS)

    Comer, Jeffrey; Aksimentiev, Aleksei

    2016-05-01

    Measurements of ionic currents through nanopores partially blocked by DNA have emerged as a powerful method for characterization of the DNA nucleotide sequence. Although the effect of the nucleotide sequence on the nanopore blockade current has been experimentally demonstrated, prediction and interpretation of such measurements remain a formidable challenge. Using atomic resolution computational approaches, here we show how the sequence, molecular conformation, and pore geometry affect the blockade ionic current in model solid-state nanopores. We demonstrate that the blockade current from a DNA molecule is determined by the chemical identities and conformations of at least three consecutive nucleotides. We find the blockade currents produced by the nucleotide triplets to vary considerably with their nucleotide sequences despite having nearly identical molecular conformations. Encouragingly, we find blockade current differences as large as 25% for single-base substitutions in ultra small (1.6 nm × 1.1 nm cross section; 2 nm length) solid-state nanopores. Despite the complex dependence of the blockade current on the sequence and conformation of the DNA triplets, we find that, under many conditions, the number of thymine bases is positively correlated with the current, whereas the number of purine bases and the presence of both purines and pyrimidines in the triplet are negatively correlated with the current. Based on these observations, we construct a simple theoretical model that relates the ion current to the base content of a solid-state nanopore. Furthermore, we show that compact conformations of DNA in narrow pores provide the greatest signal-to-noise ratio for single base detection, whereas reduction of the nanopore length increases the ionic current noise. Thus, the sequence dependence of the nanopore blockade current can be theoretically rationalized, although the predictions will likely need to be customized for each nanopore type.Measurements of ionic

  7. Next-generation proteomics faces new challenges in environmental biotechnology.

    PubMed

    Armengaud, Jean

    2016-04-01

    Environmental biotechnology relies on the exploration of novel biological systems and a thorough understanding of the underlying molecular mechanisms. Next-generation proteomics based on the latest generation of mass analyzers currently allows the recording of complete proteomes from any microorganism. Interpreting these data can be straightforward if the genome of the organism is established, or relatively easy to perform through proteogenomics approaches if a draft sequence can be obtained. However, next-generation proteomics faces new, interesting challenges when the organism is distantly related to previously characterized organisms or when mixtures of organisms have to be analyzed. New mass spectrometers and innovative bioinformatics tools are reshaping the possibilities of homology-based proteomics, proteogenomics, and metaproteomics for the characterization of biological systems. Novel time- and cost-effective screening strategies are also possible with this methodology, as exemplified by whole proteome thermal profiling and subpopulation proteomics. The complexity of environmental samples allows for unique developments of approaches and concepts. PMID:26950175

  8. Proteomic developments in the analysis of formalin-fixed tissue.

    PubMed

    Gustafsson, Ove J R; Arentz, Georgia; Hoffmann, Peter

    2015-06-01

    Retrospective proteomic studies, including those which aim to elucidate the molecular mechanisms driving cancer, require the assembly and characterization of substantial patient tissue cohorts. The difficulty of maintaining and accessing native tissue archives has prompted the development of methods to access archives of formalin-fixed tissue. Formalin-fixed tissue archives, complete with patient meta data, have accumulated for decades, presenting an invaluable resource for these retrospective studies. This review presents the current knowledge concerning formalin-fixed tissue, with descriptions of the mechanisms of formalin fixation, protein extraction, top-down proteomics, bottom-up proteomics, quantitative proteomics, phospho- and glycoproteomics as well as imaging mass spectrometry. Particular attention has been given to the inclusion of proteomic investigations of archived tumour tissue. This article is part of a Special Issue entitled: Medical Proteomics. PMID:25315853

  9. DNA sequence-dependent ionic currents in ultra-small solid-state nanopores.

    PubMed

    Comer, Jeffrey; Aksimentiev, Aleksei

    2016-05-01

    Measurements of ionic currents through nanopores partially blocked by DNA have emerged as a powerful method for characterization of the DNA nucleotide sequence. Although the effect of the nucleotide sequence on the nanopore blockade current has been experimentally demonstrated, prediction and interpretation of such measurements remain a formidable challenge. Using atomic resolution computational approaches, here we show how the sequence, molecular conformation, and pore geometry affect the blockade ionic current in model solid-state nanopores. We demonstrate that the blockade current from a DNA molecule is determined by the chemical identities and conformations of at least three consecutive nucleotides. We find the blockade currents produced by the nucleotide triplets to vary considerably with their nucleotide sequences despite having nearly identical molecular conformations. Encouragingly, we find blockade current differences as large as 25% for single-base substitutions in ultra small (1.6 nm × 1.1 nm cross section; 2 nm length) solid-state nanopores. Despite the complex dependence of the blockade current on the sequence and conformation of the DNA triplets, we find that, under many conditions, the number of thymine bases is positively correlated with the current, whereas the number of purine bases and the presence of both purines and pyrimidines in the triplet are negatively correlated with the current. Based on these observations, we construct a simple theoretical model that relates the ion current to the base content of a solid-state nanopore. Furthermore, we show that compact conformations of DNA in narrow pores provide the greatest signal-to-noise ratio for single base detection, whereas reduction of the nanopore length increases the ionic current noise. Thus, the sequence dependence of the nanopore blockade current can be theoretically rationalized, although the predictions will likely need to be customized for each nanopore type. PMID:27103233

  10. Proteomic Analysis in Type 2 Diabetes Patients before and after a Very Low Calorie Diet Reveals Potential Disease State and Intervention Specific Biomarkers

    PubMed Central

    Dharuri, Harish K.; Jeyakar, Skhandhan; Snel, Marieke; Juhasz, Peter; Lynch, Moira; Hines, Wade; Li, Xiaohong; Jazet, Ingrid M.; Adourian, Aram; Hilbers, Peter A. J.; Smit, Johannes W. A.; Van Dijk, Ko Willems

    2014-01-01

    Very low calorie diets (VLCD) with and without exercise programs lead to major metabolic improvements in obese type 2 diabetes patients. The mechanisms underlying these improvements have so far not been elucidated fully. To further investigate the mechanisms of a VLCD with or without exercise and to uncover possible biomarkers associated with these interventions, blood samples were collected from 27 obese type 2 diabetes patients before and after a 16-week VLCD (Modifast ∼450 kcal/day). Thirteen of these patients followed an exercise program in addition to the VCLD. Plasma was obtained from 27 lean and 27 obese controls as well. Proteomic analysis was performed using mass spectrometry (MS) and targeted multiple reaction monitoring (MRM) and a large scale isobaric tags for relative and absolute quantitation (iTRAQ) approach. After the 16-week VLCD, there was a significant decrease in body weight and HbA1c in all patients, without differences between the two intervention groups. Targeted MRM analysis revealed differences in several proteins, which could be divided in diabetes-associated (fibrinogen, transthyretin), obesity-associated (complement C3), and diet-associated markers (apolipoproteins, especially apolipoprotein A-IV). To further investigate the effects of exercise, large scale iTRAQ analysis was performed. However, no proteins were found showing an exercise effect. Thus, in this study, specific proteins were found to be differentially expressed in type 2 diabetes patients versus controls and before and after a VLCD. These proteins are potential disease state and intervention specific biomarkers. Trial Registration Controlled-Trials.com ISRCTN76920690 PMID:25415563

  11. Electromechanical actuation and current-induced metastable states in suspended single-crystalline VO2 nanoplatelets

    SciTech Connect

    Tselev, Alexander; Budai, John D; Strelcov, Evgheni; Tischler, Jonathan Zachary; Kolmakov, Andrei; Kalinin, Sergei V

    2011-01-01

    Current-induced electromechanical actuation enabled by the metal-insulator transition in VO{sub 2} nanoplatelets is demonstrated. The Joule heating by a sufficient current flowing through suspended nanoplatelets results in formation of heterophase domain patterns and is accompanied by nanoplatelet deformation. The actuation action can be achieved in a wide temperature range below the bulk phase transition temperature (68 C). The observed current-sustained heterophase domain structures should be interpreted as distinct metastable states in free-standing and end-clamped VO{sub 2} samples. We analyze the main prerequisites for the realization of a current-controlled actuator based on the proposed concept.

  12. New Memorandum of Understanding in Clinical Proteogenomics Between the United States and Australia - Office of Cancer Clinical Proteomics Research

    Cancer.gov

    The White House Office of the Vice President has announced the signing of three Memoranda of Understanding (MOUs) that will make available an unprecedented international dataset to advance cancer research and care. An MOU between the National Cancer Institute (NCI) at the National Institutes of Health (NIH) in the United States, and Macquarie University (MU), Children's Medical Research Institute (CMRI), Garvan Institute of Medical Research (GIMR), and Bioplatforms Australia Limited (BPA) in Australia will facilitate scientific collaborations in the field of clinical proteogenomic studies and their translation to cancer care.

  13. Liquid Chromatography-Mass Spectrometry-based Quantitative Proteomics

    SciTech Connect

    Xie, Fang; Liu, Tao; Qian, Weijun; Petyuk, Vladislav A.; Smith, Richard D.

    2011-07-22

    Liquid chromatography-mass spectrometry (LC-MS)-based quantitative proteomics has become increasingly applied for a broad range of biological applications due to growing capabilities for broad proteome coverage and good accuracy in quantification. Herein, we review the current LC-MS-based quantification methods with respect to their advantages and limitations, and highlight their potential applications.

  14. Proteomics in Animal Models of Alzheimer's and Parkinson's Diseases

    PubMed Central

    Sowell, Renã A.; Owen, Joshua B.; Butterfield, D. Allan

    2009-01-01

    The risk of developing neurodegenerative disorders such as Alzheimer's (AD) and Parkinson's (PD) diseases increases with age. AD and PD are the two most common neurodegenerative diseases that currently affect millions of persons within the United States population. While many clues about the mechanisms of these disorders have been uncovered, to date, the molecular mechanisms associated with the cause of these diseases are not completely understood. Furthermore, there are no available cures or preventative treatments for either disorder. Animal models of AD and PD, though not perfect, offer a means to gain knowledge of the basic biochemistry associated with these disorders and with drug efficacy. The field of proteomics which focuses on identifying the dynamic nature of the protein content expressed within a particular cell, tissue, or organism, has provided many insights into these disturbing disorders. Proteomic studies have revealed many pathways that are associated with disease pathogenesis and that may lead to the development of potential therapeutic targets. This review provides a discussion of key findings from AD and PD proteomics-based studies in various animal models of disease. PMID:18703168

  15. Early detection in head and neck cancer – current state and future perspectives

    PubMed Central

    Gerstner, Andreas O. H.

    2010-01-01

    Survival and quality of life in head and neck cancer are directly linked to the size of the primary tumor at first detection. In order to achieve substantial gain at these issues, both, primary prevention and secondary prevention, which is early detection of malignant lesions at a small size, have to be improved. So far, there is not only a lack in the necessary infrastructure not only in Germany, but rather worldwide, but additionally the techniques developed so far for early detection have a significance and specificity too low as to warrant safe implementation for screening programs. However, the advancements recently achieved in endoscopy and in quantitative analysis of hypocellular specimens open new perspectives for secondary prevention. Chromoendoscopy and narrow band imaging (NBI) pinpoint suspicious lesions more easily, confocal endomicroscopy and optical coherence tomography obtain optical sections through those lesions, and hyperspectral imaging classifies lesions according to characteristic spectral signatures. These techniques therefore obtain optical biopsies. Once a “bloody” biopsy has been taken, the plethora of parameters that can be quantified objectively has been increased and could be the basis for an objective and quantitative classification of epithelial lesions (multiparametric cytometry, quantitative histology). Finally, cytomics and proteomics approaches, and lab-on-the-chip technology might help to identify patients at high-risk. Sensitivity and specificity of these approaches have to be validated, yet, and some techniques have to be adapted for the specific conditions for early detection of head and neck cancer. On this background it has to be stated that it is still a long way to go until a population based screening for head and neck cancer is available. The recent results of screening for cancer of the prostate and breast highlight the difficulties implemented in such a task. PMID:22073093

  16. Proteomics: A new perspective for cancer.

    PubMed

    Shruthi, Basavaradhya Sahukar; Vinodhkumar, Palani; Selvamani

    2016-01-01

    In the past decades, several ground breaking discoveries in life science were made. The completion of sequencing the human genome certainly belongs to the key tasks successfully completed, representing a true milestone in the biomedicine. The accomplishment of the complete genome also brings along a new, even more challenging task for scientists: The characterization of the human proteome. Proteomics, the main tool for proteome research, is a relatively new and extremely dynamically evolving branch of science, focused on the evaluation of gene expression at proteome level. Due to the specific properties of proteins, current proteomics deals with different issues, such as protein identification, quantification, characterization of post-translational modification, structure and function elucidation, and description of possible interactions. This field incorporates technologies that can be applied to serum and tissue in order to extract important biological information in the form of biomarkers to aid clinicians and scientists in understanding the dynamic biology of their system of interest, such as a patient with cancer. The present review article provides a detail description of proteomics and its role in cancer research. PMID:27169098

  17. Proteomics: A new perspective for cancer

    PubMed Central

    Shruthi, Basavaradhya Sahukar; Vinodhkumar, Palani; Selvamani

    2016-01-01

    In the past decades, several ground breaking discoveries in life science were made. The completion of sequencing the human genome certainly belongs to the key tasks successfully completed, representing a true milestone in the biomedicine. The accomplishment of the complete genome also brings along a new, even more challenging task for scientists: The characterization of the human proteome. Proteomics, the main tool for proteome research, is a relatively new and extremely dynamically evolving branch of science, focused on the evaluation of gene expression at proteome level. Due to the specific properties of proteins, current proteomics deals with different issues, such as protein identification, quantification, characterization of post-translational modification, structure and function elucidation, and description of possible interactions. This field incorporates technologies that can be applied to serum and tissue in order to extract important biological information in the form of biomarkers to aid clinicians and scientists in understanding the dynamic biology of their system of interest, such as a patient with cancer. The present review article provides a detail description of proteomics and its role in cancer research. PMID:27169098

  18. Proteomics of survival structures of fungal pathogens.

    PubMed

    Loginov, Dmitry; Šebela, Marek

    2016-09-25

    Fungal pathogens are causal agents of numerous human, animal, and plant diseases. They employ various infection modes to overcome host defense systems. Infection mechanisms of different fungi have been subjected to many comprehensive studies. These investigations have been facilitated by the development of various '-omics' techniques, and proteomics has one of the leading roles in this regard. Fungal conidia and sclerotia could be considered the most important structures for pathogenesis as their germination is one of the first steps towards a host infection. They represent interesting objects for proteomic studies because of the presence of unique proteins with unexplored biotechnological potential required for pathogen viability, development and the subsequent host infection. Proteomic peculiarities of survival structures of different fungi, including those of biotechnological significance (e.g., Asperillus fumigatus, A. nidulans, Metarhizium anisopliae), in a dormant state, as well as changes in the protein production during early stages of fungal development are the subjects of the present review. We focused on biological aspects of proteomic studies of fungal survival structures rather than on an evaluation of proteomic approaches. For that reason, proteins that have been identified in this context are discussed from the point of view of their involvement in different biological processes and possible functions assigned to them. This is the first review paper summarizing recent advances in proteomics of fungal survival structures. PMID:26777984

  19. Non-Inductive Current Drive Modeling Extending Advanced Tokamak Operation to Steady State

    SciTech Connect

    Casper, T.A.; Lodestro, L.L.; Pearlstein, L.D.; Porter, G.D.; Murakami, M.; Lao, L.L.; Lin-Lui, Y.R.; St. John, H.E.

    2000-06-06

    A critical issue for sustaining high performance, negative central shear (NCS) discharges is the ability to maintain current distributions that are maximum off axis. Sustaining such hollow current profiles in steady state requires the use of non-inductively driven current sources. On the DIII-D experiment, a combination of neutral beam current drive (NBCD) and bootstrap current have been used to create transient NCS discharges. The electron cyclotron heating (ECH) and current drive (ECCD) system is currently being upgraded from three gyrotrons to six to provide more than 3MW of absorbed power in long-pulse operation to help sustain the required off-axis current drive. This upgrade SuPporrs the long range goal of DIII-D to sustain high performance discharges with high values of normalized {beta}, {beta}{sub n} = {beta}/(I{sub p}/aB{sub T}), confinement enhancement factor, H, and neutron production rates while utilizing bootstrap current fraction, f{sub bs}, in excess of 50%. At these high performance levels, the likelihood of onset of MHD modes that spoil confinement indicates the need to control plasma profiles if we are to extend this operation to long pulse or steady state. To investigate the effectiveness of the EC system and to explore operating scenarios to sustain these discharges, we use time-dependent simulations of the equilibrium, transport and stability. We explore methods to directly alter the safety factor profile, q, through direct current drive or by localized electron heating to modify the bootstrap current profile. Time dependent simulations using both experimentally determined [1] and theory-based [2] energy transport models have been done. Here, we report on simulations exploring parametric dependencies of the heating, current drive, and profiles that affect our ability to sustain stable discharges.

  20. Transient and steady-state dark current mechanisms in amorphous selenium avalanche radiation detectors

    SciTech Connect

    Kabir, M. Z.; Imam, Safayat-Al

    2013-04-15

    A theoretical model for describing bias-dependent transient and steady-state behaviors of dark current in amorphous selenium (a-Se) avalanche detector structures has been developed. The analytical model considers bulk thermal generation current from mid-gap sates, transient carrier depletion, and carrier injection from the electrodes incorporating avalanche multiplication. The proposed physics-based dark current model is compared with the published experimental results on three potential a-Se avalanche detector structures. The steady-state dark current is the minimum for the structures that have effective blocking layers for both holes and electrons. The transient decay time to reach a plateau decreases considerably with increasing electric field.

  1. Including Alternative Resources in State Renewable Portfolio Standards: Current Design and Implementation Experience

    SciTech Connect

    Heeter, J.; Bird, L.

    2012-11-01

    Currently, 29 states, the District of Columbia, and Puerto Rico have instituted a renewable portfolio standard (RPS). An RPS sets a minimum threshold for how much renewable energy must be generated in a given year. Each state policy is unique, varying in percentage targets, timetables, and eligible resources. This paper examines state experience with implementing renewable portfolio standards that include energy efficiency, thermal resources, and non-renewable energy and explores compliance experience, costs, and how states evaluate, measure, and verify energy efficiency and convert thermal energy. It aims to gain insights from the experience of states for possible federal clean energy policy as well as to share experience and lessons for state RPS implementation.

  2. What is the current state of scientific knowledge with regard to seasonal and decadal forecasting?

    NASA Astrophysics Data System (ADS)

    Smith, Doug M.; Scaife, Adam A.; Kirtman, Ben P.

    2012-03-01

    Environmental factors, such as the frequency, intensity and duration of extreme weather events, are important drivers of migration and displacement of people. There is therefore a growing need for regional climate predictions for the coming seasons to decades. This paper reviews the current state of the art of seasonal to decadal climate prediction, focusing on the potential sources of skill, forecasting techniques, current capability and future prospects.

  3. Phase-slip states in the normal-superconducting relaxation of current-biased microstrips

    SciTech Connect

    Butler, D.P.; Hsiang, T.Y.

    1987-03-01

    The authors have solved the generalized time-dependent Ginzburg-Landau (TDGL) equations of Kramer and Watts-Tobin numerically. The solutions are used to predict the relaxation behavior of a microstrip biased below its dc critical current and excited into the resistive state by the application of a supercritical current pulse of a fixed duration. They have studied the relaxation behavior of the gap parameter and voltage along the microstrip as a function of the current pulse amplitude and bias magnitude. The relaxation is found to occur through a succession of phase-slip oscillations. The relaxation behavior is determined by the initial phase-slip state created by the current pulse. The maximum resistance attained increases rapidly, then saturates at a value less than the normal state resistance. The numerical solutions exhibit a region in which a relaxation time anomaly occurs with respect to the current pulse amplitude. In this region, the more highly excited states were found to relax faster. These features of the resistive relaxation behavior are found to be in qualitative agreement with their previous experimental measurements.

  4. Phase boundary of spin-polarized-current state of electrons in bilayer graphene

    NASA Astrophysics Data System (ADS)

    Yan, Xin-Zhong; Ma, Yinfeng; Ting, C. S.

    2016-06-01

    Using a four-band Hamiltonian, we study the phase boundary of spin-polarized-current state (SPCS) of interacting electrons in bilayer graphene. The model of spin-polarized-current state has previously been shown to resolve a number of experimental puzzles in bilayer graphene. The phase boundaries of the SPCS with and without the external voltage between the two layers are obtained in this work. An unusual phase boundary where there are two transition temperatures for a given carrier concentration is found at finite external voltage. The physics of this phenomenon is explained.

  5. On phase/current components of entropy/information descriptors of molecular states

    NASA Astrophysics Data System (ADS)

    Nalewajski, Roman F.

    2014-10-01

    Quantum-generalised descriptors of the information content of electronic states in molecules are proposed, in which non-classical (current) terms complement classical (probability) functionals of the ordinary information theory. The relation between densities of the familiar classical Fisher and Shannon information/entropy measures is applied to determine their non-classical complements. The quantum supplement of the classical Shannon entropy describes the average magnitude of the phase distribution, while the current term in the Fisher measure accounts for the gradient content of the state phase function. Illustrative applications of these quantum information concepts are presented and thermodynamical analogies are commented upon. The particle-density-constrained (vertical) and -unconstrained (horizontal) equilibria in molecules and their fragments are explored and the corresponding equilibrium 'thermodynamic' phases are determined. A separation of the density (modulus) and current (phase) factors of general many-electron states is effected using the Harriman-Zumbach-Maschke construction of antisymmetric states yielding the specified electron density. The phenomenological framework in spirit of the non-equilibrium thermodynamical description is proposed. It accounts for both the density and current degrees of freedom of molecular states. The associated entropy source in the information continuity equation is derived.

  6. Dominant male song performance reflects current immune state in a cooperatively breeding songbird.

    PubMed

    York, Jenny E; Radford, Andrew N; Groothuis, Ton G; Young, Andrew J

    2016-02-01

    Conspicuous displays are thought to have evolved as signals of individual "quality", though precisely what they encode remains a focus of debate. While high quality signals may be produced by high quality individuals due to "good genes" or favourable early-life conditions, whether current immune state also impacts signalling performance remains poorly understood, particularly in social species. Here, we experimentally demonstrate that male song performance is impaired by immune system activation in the cooperatively breeding white-browed sparrow weaver (Plocepasser mahali). We experimentally activated the immune system of free-living dominant males via subcutaneous injection of phytohemagglutinin (PHA) and contrasted its effects with those of a control (phosphate buffered saline) injection. PHA-challenged males showed significant reductions in both the duration and the rate of their song performance, relative to controls, and this could not be readily attributed to effects of the challenge on body mass, as no such effects were detected. Furthermore, male song performance prior to immune-challenge predicted the scale of the inflammatory response to the challenge. Our findings suggest that song performance characteristics are impacted by current immune state. This link between current state and signal performance might therefore contribute to enforcing the honesty of signal performance characteristics. Impacts of current state on signaling may be of particular importance in social species, where subordinates may benefit from an ability to identify and subsequently challenge same-sex dominants in a weakened state. PMID:26811745

  7. Microbial community proteomics for characterizing the range of metabolic functions and activities of human gut microbiota

    DOE PAGESBeta

    Xiong, Weili; Abraham, Paul E.; Li, Zhou; Pan, Chongle; Robert L. Hettich

    2015-01-01

    We found that the human gastrointestinal (GI) tract is a complex, dynamic ecosystem that consists of a carefully tuned balance of human host and microbiota membership. The microbiome component is not insignificant, but rather provides important functions that are absolutely critical to many aspects of human health, including nutrient transformation and absorption, drug metabolism, pathogen defense, and immune system development. Microbial community proteomics (sometimes referred to as metaproteomics) provides a powerful approach to measure the range and details of human gut microbiota functions and metabolic activities, revealing information about microbiome development and stability especially with regard to human health vs.more » disease states. In most cases, both microbial and human proteins are extracted from fecal samples and then measured by the high performance MS-based proteomics technology. We review the field of human gut microbiome community proteomics, with a focus on the experimental and informatics considerations involved in characterizing systems that range from low complexity defined model gut microbiota in gnotobiotic mice, to the simple gut microbiota in the GI tract of newborn infants, and finally to the complex gut microbiota in adults. Moreover, the current state-of-the-art in experimental and bioinformatics capabilities for community proteomics enable a detailed measurement of the gut microbiota, yielding valuable insights into the broad functional profiles of even complex microbiota. Future developments are likely to expand into improved analysis throughput and coverage depth, as well as post-translational modification characterizations.« less

  8. Microbial community proteomics for characterizing the range of metabolic functions and activities of human gut microbiota

    SciTech Connect

    Xiong, Weili; Abraham, Paul E.; Li, Zhou; Pan, Chongle; Robert L. Hettich

    2015-01-01

    We found that the human gastrointestinal (GI) tract is a complex, dynamic ecosystem that consists of a carefully tuned balance of human host and microbiota membership. The microbiome component is not insignificant, but rather provides important functions that are absolutely critical to many aspects of human health, including nutrient transformation and absorption, drug metabolism, pathogen defense, and immune system development. Microbial community proteomics (sometimes referred to as metaproteomics) provides a powerful approach to measure the range and details of human gut microbiota functions and metabolic activities, revealing information about microbiome development and stability especially with regard to human health vs. disease states. In most cases, both microbial and human proteins are extracted from fecal samples and then measured by the high performance MS-based proteomics technology. We review the field of human gut microbiome community proteomics, with a focus on the experimental and informatics considerations involved in characterizing systems that range from low complexity defined model gut microbiota in gnotobiotic mice, to the simple gut microbiota in the GI tract of newborn infants, and finally to the complex gut microbiota in adults. Moreover, the current state-of-the-art in experimental and bioinformatics capabilities for community proteomics enable a detailed measurement of the gut microbiota, yielding valuable insights into the broad functional profiles of even complex microbiota. Future developments are likely to expand into improved analysis throughput and coverage depth, as well as post-translational modification characterizations.

  9. Aptamer-Based Multiplexed Proteomic Technology for Biomarker Discovery

    PubMed Central

    Gold, Larry; Ayers, Deborah; Bertino, Jennifer; Bock, Christopher; Bock, Ashley; Brody, Edward N.; Carter, Jeff; Dalby, Andrew B.; Eaton, Bruce E.; Fitzwater, Tim; Flather, Dylan; Forbes, Ashley; Foreman, Trudi; Fowler, Cate; Gawande, Bharat; Goss, Meredith; Gunn, Magda; Gupta, Shashi; Halladay, Dennis; Heil, Jim; Heilig, Joe; Hicke, Brian; Husar, Gregory; Janjic, Nebojsa; Jarvis, Thale; Jennings, Susan; Katilius, Evaldas; Keeney, Tracy R.; Kim, Nancy; Koch, Tad H.; Kraemer, Stephan; Kroiss, Luke; Le, Ngan; Levine, Daniel; Lindsey, Wes; Lollo, Bridget; Mayfield, Wes; Mehan, Mike; Mehler, Robert; Nelson, Sally K.; Nelson, Michele; Nieuwlandt, Dan; Nikrad, Malti; Ochsner, Urs; Ostroff, Rachel M.; Otis, Matt; Parker, Thomas; Pietrasiewicz, Steve; Resnicow, Daniel I.; Rohloff, John; Sanders, Glenn; Sattin, Sarah; Schneider, Daniel; Singer, Britta; Stanton, Martin; Sterkel, Alana; Stewart, Alex; Stratford, Suzanne; Vaught, Jonathan D.; Vrkljan, Mike; Walker, Jeffrey J.; Watrobka, Mike; Waugh, Sheela; Weiss, Allison; Wilcox, Sheri K.; Wolfson, Alexey; Wolk, Steven K.; Zhang, Chi; Zichi, Dom

    2010-01-01

    Background The interrogation of proteomes (“proteomics”) in a highly multiplexed and efficient manner remains a coveted and challenging goal in biology and medicine. Methodology/Principal Findings We present a new aptamer-based proteomic technology for biomarker discovery capable of simultaneously measuring thousands of proteins from small sample volumes (15 µL of serum or plasma). Our current assay measures 813 proteins with low limits of detection (1 pM median), 7 logs of overall dynamic range (∼100 fM–1 µM), and 5% median coefficient of variation. This technology is enabled by a new generation of aptamers that contain chemically modified nucleotides, which greatly expand the physicochemical diversity of the large randomized nucleic acid libraries from which the aptamers are selected. Proteins in complex matrices such as plasma are measured with a process that transforms a signature of protein concentrations into a corresponding signature of DNA aptamer concentrations, which is quantified on a DNA microarray. Our assay takes advantage of the dual nature of aptamers as both folded protein-binding entities with defined shapes and unique nucleotide sequences recognizable by specific hybridization probes. To demonstrate the utility of our proteomics biomarker discovery technology, we applied it to a clinical study of chronic kidney disease (CKD). We identified two well known CKD biomarkers as well as an additional 58 potential CKD biomarkers. These results demonstrate the potential utility of our technology to rapidly discover unique protein signatures characteristic of various disease states. Conclusions/Significance We describe a versatile and powerful tool that allows large-scale comparison of proteome profiles among discrete populations. This unbiased and highly multiplexed search engine will enable the discovery of novel biomarkers in a manner that is unencumbered by our incomplete knowledge of biology, thereby helping to advance the next generation of

  10. Advanced proteomic liquid chromatography

    SciTech Connect

    Xie, Fang; Smith, Richard D.; Shen, Yufeng

    2012-10-26

    Liquid chromatography coupled with mass spectrometry is the predominant platform used to analyze proteomics samples consisting of large numbers of proteins and their proteolytic products (e.g., truncated polypeptides) and spanning a wide range of relative concentrations. This review provides an overview of advanced capillary liquid chromatography techniques and methodologies that greatly improve separation resolving power and proteomics analysis coverage, sensitivity, and throughput.

  11. Mass Spectrometry Applied to Bottom-Up Proteomics: Entering the High-Throughput Era for Hypothesis Testing.

    PubMed

    Gillet, Ludovic C; Leitner, Alexander; Aebersold, Ruedi

    2016-06-12

    Proteins constitute a key class of molecular components that perform essential biochemical reactions in living cells. Whether the aim is to extensively characterize a given protein or to perform high-throughput qualitative and quantitative analysis of the proteome content of a sample, liquid chromatography coupled to tandem mass spectrometry has become the technology of choice. In this review, we summarize the current state of mass spectrometry applied to bottom-up proteomics, the approach that focuses on analyzing peptides obtained from proteolytic digestion of proteins. With the recent advances in instrumentation and methodology, we show that the field is moving away from providing qualitative identification of long lists of proteins to delivering highly consistent and accurate quantification values for large numbers of proteins across large numbers of samples. We believe that this shift will have a profound impact for the field of proteomics and life science research in general. PMID:27049628

  12. Mass Spectrometry Applied to Bottom-Up Proteomics: Entering the High-Throughput Era for Hypothesis Testing

    NASA Astrophysics Data System (ADS)

    Gillet, Ludovic C.; Leitner, Alexander; Aebersold, Ruedi

    2016-06-01

    Proteins constitute a key class of molecular components that perform essential biochemical reactions in living cells. Whether the aim is to extensively characterize a given protein or to perform high-throughput qualitative and quantitative analysis of the proteome content of a sample, liquid chromatography coupled to tandem mass spectrometry has become the technology of choice. In this review, we summarize the current state of mass spectrometry applied to bottom-up proteomics, the approach that focuses on analyzing peptides obtained from proteolytic digestion of proteins. With the recent advances in instrumentation and methodology, we show that the field is moving away from providing qualitative identification of long lists of proteins to delivering highly consistent and accurate quantification values for large numbers of proteins across large numbers of samples. We believe that this shift will have a profound impact for the field of proteomics and life science research in general.

  13. Business-IT Alignment: A Current-State Evaluation of Strategic Alignment within the Hospital Organization

    ERIC Educational Resources Information Center

    Evers, Kevin W.

    2010-01-01

    More than thirty years of research has shown that the practical value of business-IT alignment is significant and that its importance derives from strategic impact on business outcomes. The purpose of this exploratory study is to identify the current-state of business-IT alignment maturity within the hospital organization. Data for this study was…

  14. The State of Knowledge of Outdoor Orientation Programs: Current Practices, Research, and Theory

    ERIC Educational Resources Information Center

    Bell, Brent J.; Gass, Michael A.; Nafziger, Christopher S.; Starbuck, J. David

    2014-01-01

    Outdoor orientation programs represent a prominent area of experiential education with over 25,000 participants annually. More than 191 outdoor orientation programs currently operate in the United States and Canada. The research examining outdoor orientation programs consists of 25 peer-reviewed published studies and 11 dissertations. A new theory…

  15. A Sociological Demographic Analysis of the Current State and Evolution of the Family

    ERIC Educational Resources Information Center

    Golod, S. I.

    2008-01-01

    Starting in the 1960s, researchers in many countries have expressed concern over the state of crisis of monogamy, addressing the phenomenon as a direct function of global social transformations. The author finds it is difficult to agree with the negative assessment of the current status of the family, noting that centuries of evidence confirm the…

  16. CURRENT STATE OF PREDICTING THE RESPIRATORY ALLERGY POTENTIAL OF CHEMICALS: WHAT ARE THE ISSUES?

    EPA Science Inventory

    Current State of Predicting the Respiratory Allergy Potential of Chemicals: What Are the Issues? M I. Gilmour1 and S. E. Loveless2, 1USEPA, Research Triangle Park, NC and 2DuPont Haskell Laboratory, Newark, DE.

    Many chemicals are clearly capable of eliciting immune respon...

  17. Profile of the Foreign-Born Population in the United States: 2000. Current Population Reports.

    ERIC Educational Resources Information Center

    Schmidley, Dianne

    This report presents data on a wide range of geographic, demographic, social, economic, and housing characteristics for the foreign-born population of the United States. Data for the native population are included for comparison. Data come from the March 2000 Current Population Survey. The core of the report is 22 sections presenting information…

  18. "Nobody Told Us about What Happened": The Current State of Holocaust Education in Romania

    ERIC Educational Resources Information Center

    Misco, Tomas

    2008-01-01

    This research study sought to understand the current state of Holocaust education in Romanian classrooms and how sociocultural and institutional forces influence its treatment. By identifying the obstacles, challenges, and successes of Holocaust education in Romania, this study can both disseminate the techniques and conditions that bring about…

  19. The Current State of Empirical Support for the Pharmacological Treatment of Selective Mutism

    ERIC Educational Resources Information Center

    Carlson, John S.; Mitchell, Angela D.; Segool, Natasha

    2008-01-01

    This article reviews the current state of evidence for the psychopharmacological treatment of children diagnosed with selective mutism within the context of its link to social anxiety disorder. An increased focus on potential medication treatment for this disorder has resulted from significant monetary and resource limitations in typical practice,…

  20. Students and Scholars from the People's Republic of China Currently in the United States. Survey Summary.

    ERIC Educational Resources Information Center

    National Association for Foreign Students Affairs, Washington, DC. China Education Clearinghouse.

    Information concerning students and scholars from the People's Republic of China (PRC) currently in the United States was obtained through a survey of U.S. colleges and universities where the Chinese are studying or conducting research. Responses received from 133 of the 168 U.S. institutions that were sent questionnaires indicated that there were…

  1. CURRENT STATE OF FOOD ENGINEERING EDUCATION – DEPARTMENTAL AND STUDENT PERCEPTIONS

    Technology Transfer Automated Retrieval System (TEKTRAN)

    During the last two years, the FPE-80 (Food Engineering Education Priorities Group) committee has undertaken an initiative to gather information regarding the current state of food engineering education in the U.S. In order to understand the needs of students, academic units, and industrial employer...

  2. Evaluation of current state of agricultural land using problem-oriented fuzzy indicators in GIS environment

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Current state of agricultural lands is defined under influence of processes in soil, plants and atmosphere and is described by observation data, complicated models and subjective opinion of experts. Problem-oriented indicators summarize this information in useful form for decision of the same specif...

  3. Globalization of Gerontology Education: Current Practices and Perceptions for Graduate Gerontology Education in the United States

    ERIC Educational Resources Information Center

    Mwangi, Samuel M.; Yamashita, Takashi; Ewen, Heidi H.; Manning, Lydia K.; Kunkel, Suzanne R.

    2012-01-01

    The purpose of this study is to document current practices and understandings about globalization of gerontology education in the United States. Better understanding of aging requires international perspectives in global communities. However, little is known about how globalization of gerontology education is practiced in U.S. graduate-level…

  4. Educational Attainment in the United States: 2009. Population Characteristics. Current Population Reports. P20-566

    ERIC Educational Resources Information Center

    Ryan, Camille L.; Siebens, Julie

    2012-01-01

    This report provides a portrait of educational attainment in the United States based on data collected in the 2009 American Community Survey (ACS) and the 2005-2009 ACS 5-year estimates. It also uses data from the Annual Social and Economic Supplement (ASEC) to the Current Population Survey (CPS) collected in 2009 and earlier, as well as monthly…

  5. Visible or Invisible? Korean High School Students' Current Schooling Experiences in the United States

    ERIC Educational Resources Information Center

    Yoon, Bogum; Haag, Claudia

    2010-01-01

    This qualitative study examined the current schooling experiences of eight Korean high school students in the United States. By comparing and contrasting recent immigrant adolescents and 1.5/2nd generation students, the purpose of this study was to explore how their identities as Koreans or Korean Americans were formed and shifted while they…

  6. Early Childhood Inclusion in the United States: Goals, Current Status, and Future Directions

    ERIC Educational Resources Information Center

    Guralnick, Michael J.; Bruder, Mary Beth

    2016-01-01

    The current status and future directions of early childhood inclusion in the United States are discussed from the perspective of 4 key goals: access, accommodations and feasibility, developmental progress, and social integration. Recommendations are put forward to promote inclusion goals emphasizing administrative structures, personnel…

  7. Current State of Environmental Education in Mexico: A Study on Practices, Audiences, Settings, and Topics

    ERIC Educational Resources Information Center

    Marcos-Iga, Jose; Shaw, William

    2011-01-01

    Environmental education in Mexico takes many forms and plays a wide variety of roles. Through an online survey, we addressed the need to present a wider picture on the current state of environmental education practices in Mexico: Who is engaging in environmental education practices, how important is it for their organization, who are they…

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

    PubMed

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

    2016-06-01

    Proteomics is one of the pivotal next-generation biotechnologies in the current "postgenomics" era. Little is known about the ways in which innovative proteomics science is navigating the complex socio-political space between laboratory and society. It cannot be assumed that the trajectory between proteomics laboratory and society is linear and unidirectional. Concerned about public accountability and hopes for knowledge-based innovations, funding agencies and citizens increasingly expect that emerging science and technologies, such as proteomics, are effectively translated and disseminated as innovation in society. Here, we describe translation strategies promoted in the knowledge translation (KT) and science communication literatures and examine the use of these strategies within the field of proteomics. Drawing on data generated from qualitative interviews with proteomics scientists and ethnographic observation of international proteomics conferences over a 5-year period, we found that proteomics science incorporates a variety of KT strategies to reach knowledge users outside the field. To attain the full benefit of KT, however, proteomics scientists must challenge their own normative assumptions and approaches to innovation dissemination-beyond the current paradigm relying primarily on publication for one's scientific peers within one's field-and embrace the value of broader (interdisciplinary) KT strategies in promoting the uptake of their research. Notably, the Human Proteome Organization (HUPO) is paying increasing attention to a broader range of KT strategies, including targeted dissemination, integrated KT, and public outreach. We suggest that increasing the variety of KT strategies employed by proteomics scientists is timely and would serve well the omics system sciences community. PMID:27223900

  9. Pan-proteomics, a concept for unifying quantitative proteome measurements when comparing closely-related bacterial strains.

    PubMed

    Broadbent, James A; Broszczak, Daniel A; Tennakoon, Imalka U K; Huygens, Flavia

    2016-04-01

    The comparison of proteomes between genetically heterogeneous bacterial strains may offer valuable insights into physiological diversity and function, particularly where such variation aids in the survival and virulence of clinically-relevant strains. However, reports of such comparisons frequently fail to account for underlying genetic variance. As a consequence, the current knowledge regarding bacterial physiological diversity at the protein level may be incomplete or inaccurate. To address this, greater consideration must be given to the impact of genetic heterogeneity on proteome comparisons. This may be possible through the use of pan-proteomics, an analytical concept that permits the ability to qualitatively and quantitatively compare the proteomes of genetically heterogeneous organisms. Limited examples of this emerging technology highlight currently unmet analytical challenges. In this article we define pan-proteomics, where its value lies in microbiology, and discuss the technical considerations critical to its successful execution and potential future application. PMID:26889693

  10. Computational Study on the Steady-state Impedance of Saturated-core Superconducting Fault Current Limiter

    NASA Astrophysics Data System (ADS)

    Zhang, C.; Tang, Y.; Liang, S.; Ren, L.; Wang, Z.; Xu, Y.

    This paper presents the electromagnetic analysis of a high voltage saturated-core superconducting fault current limiter (SCSFCL). The numerical analyses of a three-dimensional (3D) model is shown, and the specific parameters are given. The model focus on the steady-state impedance of the limiter when connected to the power grid. It analyzed the dependence of steady-state impedance on the AC coil current, and the relationship between oil gap and coil inductance. The results suggest that, adding oil gap between slice of silicon steel can reduce the core cross-section, restrain the ultraharmonic and decrease the steady-state impedance. As the core cross-section of AC limb decreased from 4344 cm2 to 3983 cm2, the total harmonic distortion for voltage decreased from 2.4% to 1.8%, and the impedance decreased from 1.082 Ω to 1.069 Ω(Idc=400A,Iac=1296A).

  11. Reaction kinetic parameters for ion transport from steady-state current-voltage curves.

    PubMed Central

    Gradmann, D; Klieber, H G; Hansen, U P

    1987-01-01

    This study demonstrates possible ways to estimate the rate constants of reaction kinetic models for ion transport from steady-state current-voltage data as measured at various substrate concentrations. This issue is treated theoretically by algebraic reduction and extension of a reaction kinetic four-state model for uniport. Furthermore, an example for application is given; current-voltage data from an open K+ selective channel (Schroeder, J.I., R. Hedrich, and J.M. Fernandez, 1984, Nature (Lond.), 312:361-362) supplemented by some new data have been evaluated. The analysis yields absolute numerical estimates of the 14 rate constants of a six-state model, which is discussed in a wider context. PMID:2437973

  12. A universal steady state I-V relationship for membrane current

    NASA Technical Reports Server (NTRS)

    Chernyak, Y. B.; Cohen, R. J. (Principal Investigator)

    1995-01-01

    A purely electrical mechanism for the gating of membrane ionic channel gives rise to a simple I-V relationship for membrane current. Our approach is based on the known presence of gating charge, which is an established property of the membrane channel gating. The gating charge is systematically treated as a polarization of the channel protein which varies with the external electric field and modifies the effective potential through which the ions migrate in the channel. Two polarization effects have been considered: 1) the up or down shift of the whole potential function, and 2) the change in the effective electric field inside the channel which is due to familiar effect of the effective reduction of the electric field inside a dielectric body because of the presence of surface charges on its surface. Both effects are linear in the channel polarization. The ionic current is described by a steady state solution of the Nernst-Planck equation with the potential directly controlled by the gating charge system. The solution describes reasonably well the steady state and peak-current I-V relationships for different channels, and when applied adiabatically, explains the time lag between the gating charge current and the rise of the ionic current. The approach developed can be useful as an effective way to model the ionic currents in axons, cardiac cells and other excitable tissues.

  13. Heating and current drive requirements towards steady state operation in ITER

    SciTech Connect

    Poli, F. M.; Kessel, C. E.; Gorelenkova, M.; Bonoli, P. T.; Batchelor, D. B.; Harvey, B.; Petrov, Y.

    2014-02-12

    Steady state scenarios envisaged for ITER aim at optimizing the bootstrap current, while maintaining sufficient confinement and stability to provide the necessary fusion yield. Non-inductive scenarios will need to operate with Internal Transport Barriers (ITBs) in order to reach adequate fusion gain at typical currents of 9 MA. However, the large pressure gradients associated with ITBs in regions of weak or negative magnetic shear can be conducive to ideal MHD instabilities, reducing the no-wall limit. The E × B flow shear from toroidal plasma rotation is expected to be low in ITER, with a major role in the ITB dynamics being played by magnetic geometry. Combinations of H/CD sources that maintain weakly reversed magnetic shear profiles throughout the discharge are the focus of this work. Time-dependent transport simulations indicate that, with a trade-off of the EC equatorial and upper launcher, the formation and sustainment of quasi-steady state ITBs could be demonstrated in ITER with the baseline heating configuration. However, with proper constraints from peeling-ballooning theory on the pedestal width and height, the fusion gain and the maximum non-inductive current are below the ITER target. Upgrades of the heating and current drive system in ITER, like the use of Lower Hybrid current drive, could overcome these limitations, sustaining higher non-inductive current and confinement, more expanded ITBs which are ideal MHD stable.

  14. Analysis of transient state in HTS tapes under ripple DC load current

    NASA Astrophysics Data System (ADS)

    Stepien, M.; Grzesik, B.

    2014-05-01

    The paper concerns the analysis of transient state (quench transition) in HTS tapes loaded with the current having DC component together with a ripple component. Two shapes of the ripple were taken into account: sinusoidal and triangular. Very often HTS tape connected to a power electronic current supply (i.e. superconducting coil for SMES) that delivers DC current with ripples and it needs to be examined under such conditions. Additionally, measurements of electrical (and thermal) parameters under such ripple excitation is useful to tape characterization in broad range of load currents. The results presented in the paper were obtained using test bench which contains programmable DC supply and National Instruments data acquisition system. Voltage drops and load currents were measured vs. time. Analysis of measured parameters as a function of the current was used to tape description with quench dynamics taken into account. Results of measurements were also used to comparison with the results of numerical modelling based on FEM. Presented provisional results show possibility to use results of measurements in transient state to prepare inverse models of superconductors and their detailed numerical modelling.

  15. Human saliva proteome: an overview

    NASA Astrophysics Data System (ADS)

    Griffin, Timothy J.

    2014-06-01

    Human saliva contains a rich mixture of biomolecules. Proteins are a major component of this mixture. Given their role as the molecular effectors within biological systems, ranging from catalysis to transport to structure, proteins have great potential as biomarkers of health and disease. The ability to collect these salivary biomarkers easily using non-invasive means makes saliva proteins even more attractive for diagnostic applications. Thousands of proteins are now to be known to be present in human saliva - discovered using proteomic technologies. Emerging technologies are now making it possible to go beyond large-scale cataloging of salivary proteins. These include approaches to catalog protein contributions from the community of microorganisms residing in the oral cavity (metaproteomics) that may reflect the health state of the human host. New mass spectrometry-based proteomics methods are also emerging, shifting the emphasis from large-scale discovery experiments to hypothesis-driven assays for profiling proteins of interest within saliva, enabling validation of their association with specific health conditions. This paper provides a brief overview of efforts to catalog the proteome of human saliva. Recent developments making possible characterization of the metaproteome of human saliva will be discussed, and technologies driving new mass spectrometry-based assays for targeted analysis of proteins within complex samples, such as saliva.

  16. Occupation probabilities and current densities of bulk and edge states of a Floquet topological insulator

    NASA Astrophysics Data System (ADS)

    Dehghani, Hossein; Mitra, Aditi

    2016-05-01

    Results are presented for the occupation probabilities and current densities of bulk and edge states of half-filled graphene in a cylindrical geometry and irradiated by a circularly polarized laser. It is assumed that the system is closed and that the laser has been switched on as a quench. Laser parameters corresponding to some representative topological phases are studied: one where the Chern number of the Floquet bands equals the number of chiral edge modes, a second where anomalous edge states appear in the Floquet Brillouin zone boundaries, and a third where the Chern number is zero, yet topological edge states appear at the center and boundaries of the Floquet Brillouin zone. Qualitative differences are found for the high-frequency off-resonant and low-frequency on-resonant laser with edge states arising due to resonant processes occupied with a high effective temperature on the one hand, while edge states arising due to off-resonant processes occupied with a low effective temperature on the other. For an ideal half-filled system where only one of the bands in the Floquet Brillouin zone is occupied and the other empty, particle-hole and inversion symmetry of the Floquet Hamiltonian implies zero current density. However the laser switch-on protocol breaks the inversion symmetry, resulting in a net cylindrical sheet of current density at steady state. Due to the underlying chirality of the system, this current density profile is associated with a net charge imbalance between the top and bottom of the cylinders.

  17. Current State of Knowledge in Microbial Degradation of Polycyclic Aromatic Hydrocarbons (PAHs): A Review

    PubMed Central

    Ghosal, Debajyoti; Ghosh, Shreya; Dutta, Tapan K.; Ahn, Youngho

    2016-01-01

    purpose of this review is to provide an overview of current knowledge of bacteria, halophilic archaea, fungi and algae mediated degradation/transformation of PAHs. In addition, factors affecting PAHs degradation in the environment, recent advancement in genetic, genomic, proteomic and metabolomic techniques are also highlighted with an aim to facilitate the development of a new insight into the bioremediation of PAH in the environment.

  18. Current Pressure Transducer Application of Model-based Prognostics Using Steady State Conditions

    NASA Technical Reports Server (NTRS)

    Teubert, Christopher; Daigle, Matthew J.

    2014-01-01

    Prognostics is the process of predicting a system's future states, health degradation/wear, and remaining useful life (RUL). This information plays an important role in preventing failure, reducing downtime, scheduling maintenance, and improving system utility. Prognostics relies heavily on wear estimation. In some components, the sensors used to estimate wear may not be fast enough to capture brief transient states that are indicative of wear. For this reason it is beneficial to be capable of detecting and estimating the extent of component wear using steady-state measurements. This paper details a method for estimating component wear using steady-state measurements, describes how this is used to predict future states, and presents a case study of a current/pressure (I/P) Transducer. I/P Transducer nominal and off-nominal behaviors are characterized using a physics-based model, and validated against expected and observed component behavior. This model is used to map observed steady-state responses to corresponding fault parameter values in the form of a lookup table. This method was chosen because of its fast, efficient nature, and its ability to be applied to both linear and non-linear systems. Using measurements of the steady state output, and the lookup table, wear is estimated. A regression is used to estimate the wear propagation parameter and characterize the damage progression function, which are used to predict future states and the remaining useful life of the system.

  19. Interpreting current-induced spin polarization in topological insulator surface states

    NASA Astrophysics Data System (ADS)

    Li, Pengke; Appelbaum, Ian

    2016-06-01

    Several recent experiments on three-dimensional topological insulators claim to observe a large charge current-induced nonequilibrium ensemble spin polarization of electrons in the helical surface state. We present a comprehensive criticism of such claims, using both theory and experiment: First, we clarify the interpretation of quantities extracted from these measurements by deriving standard expressions from a Boltzmann transport equation approach in the relaxation-time approximation at zero and finite temperature to emphasize our assertion that, despite high in-plane spin projection, obtainable current-induced ensemble spin polarization is minuscule. Second, we use a simple experiment to demonstrate that magnetic field-dependent open-circuit voltage hysteresis (identical to those attributed to current-induced spin polarization in topological insulator surface states) can be generated in analogous devices where current is driven through thin films of a topologically trivial metal. This result ipso facto discredits the naive interpretation of previous experiments with TIs, which were used to claim observation of helicity, i.e., spin-momentum locking in the topologically protected surface state.

  20. Zero-field Dissipationless Chiral Edge Current in Quantum Anomalous Hall State

    NASA Astrophysics Data System (ADS)

    Chang, Cui-Zu; Zhao, Weiwei; Kim, Duk Y.; Wei, Peng; Jain, J. K.; Liu, Chaoxing; Chan, Moses H. W.; Moodera, Jagadeesh S.

    The quantum anomalous Hall (QAH) state is predicted to possess, at zero magnetic field, chiral edge channels that conduct spin polarized current without dissipation, and thus holds great promise for future high-performance information processing. In this talk, we will discuss our transport experiments that probe the QAH state with gate bias and temperature dependences, by local and nonlocal magnetoresistance measurements. This allows us to unambiguously distinguish the dissipationless edge transport from transport via other dissipative channels in the QAH system. Our experiments confirm a fundamental feature of the QAH state, namely the dissipationless transport by edge channels in zero applied fields, which will be crucial for future chiral interconnected electric and spintronic applications. This research is supported by the NSF Grants (DMR-1420620, Penn State MRSEC; in MIT by DMR-1207469 and the STC Center for Integrated Quantum Materials under NSF Grant DMR-1231319) and by ONR Grant N00014-13-1-0301.

  1. Degradation of Leakage Currents in Solid Tantalum Capacitors Under Steady-State Bias Conditions

    NASA Technical Reports Server (NTRS)

    Teverovsky, Alexander A.

    2010-01-01

    Degradation of leakage currents in various types of solid tantalum capacitors under steady-state bias conditions was investigated at temperatures from 105 oC to 170 oC and voltages up to two times the rated voltage. Variations of leakage currents with time under highly accelerated life testing (HALT) and annealing, thermally stimulated depolarization currents, and I-V characteristics were measured to understand the conduction mechanism and the reason for current degradation. During HALT the currents increase gradually up to three orders of magnitude in some cases, and then stabilize with time. This degradation is reversible and annealing can restore the initial levels of leakage currents. The results are attributed to migration of positively charged oxygen vacancies in tantalum pentoxide films that diminish the Schottky barrier at the MnO2/Ta2O5 interface and increase electron injection. A simple model allows for estimation of concentration and mobility of oxygen vacancies based on the level of current degradation.

  2. Proteomic Findings in Melanoma

    PubMed Central

    Sengupta, Deepanwita; Tackett, Alan J

    2016-01-01

    Although the emergence of proteomics as an independent branch of science is fairly recent, within a short period of time it has contributed substantially in various disciplines. The tool of mass spectrometry has become indispensable in the analysis of complex biological samples. Clinical applications of proteomics include detection of predictive and diagnostic markers, understanding mechanism of action of drugs as well as resistance mechanisms against them and assessment of therapeutic efficacy and toxicity of drugs in patients. Here, we have summarized the major contributions of proteomics towards the study of melanoma, which is a deadly variety of skin cancer with a high mortality rate. PMID:27274624

  3. A proteomic glimpse into human ureter proteome

    PubMed Central

    Hirao, Yoshitoshi; Elguoshy, Amr; Xu, Bo; Zhang, Ying; Fujinaka, Hidehiko; Yamamoto, Keiko; Yates, John R.; Yamamoto, Tadashi

    2015-01-01

    Urine has evolved as one of the most important biofluids in clinical proteomics due to its noninvasive sampling and its stability. Yet, it is used in clinical diagnostics of several disorders by detecting changes in its components including urinary protein/polypeptide profile. Despite the fact that majority of proteins detected in urine are primarily originated from the urogenital (UG) tract, determining its precise source within the UG tract remains elusive. In this article, we performed a comprehensive analysis of ureter proteome to assemble the first unbiased ureter dataset. Next, we compared these data to urine, urinary exosome, and kidney mass spectrometric datasets. Our result concluded that among 2217 nonredundant ureter proteins, 751 protein candidates (33.8%) were detected in urine as urinary protein/polypeptide or exosomal protein. On the other hand, comparing ureter protein hits (48) that are not shown in corresponding databases to urinary bladder and prostate human protein atlas databases pinpointed 21 proteins that might be unique to ureter tissue. In conclusion, this finding offers future perspectives for possible identification of ureter disease‐associated biomarkers such as ureter carcinoma. In addition, the ureter proteomic dataset published in this article will provide a valuable resource for researchers working in the field of urology and urine biomarker discovery. All MS data have been deposited in the ProteomeXchange with identifier PXD002620 (http://proteomecentral.proteomexchange.org/dataset/PXD002620). PMID:26442468

  4. Conservation assessment of current and proposed nature reserves of Tamaulipas state, Mexico

    USGS Publications Warehouse

    Cantu, C.; Gerald, Wright R.; Michael, Scott J.; Strand, Espen

    2003-01-01

    The Mexican state of Tamaulipas located in the northeastern portion of the country currently has five state nature reserves covering slightly less than 3% of its land area. These reserves were established for a variety of reasons, many unrelated to the protection of biological resources. In 2000 in response to a growing concern about the lack of organized conservation reserve planning to protect the important biological and physical features of Mexico, the Mexican Commission for Knowledge and Use of Biodiversity (CONABIO) proposed 13 new terrestrial reserves for Tamaulipas. If established these new reserves would increase the proportion of terrestrial protected lands in the state to over 21%. We compiled a geographic information system (GIS) using existing digital thematic maps of physical and biological features to examine how the existing and proposed reserves might serve to protect the biodiversity and physical features of the state. We found that most of the existing protected sites occur in areas with elevations > 1000-2000 m with temperate climate and dominated by pine forest, oak forest, and cloud forest vegetation cover types. The state's dominant biotic region - low elevation coastal plain with tropical and arid climate types and xeric scrub vegetation - is disproportionately underrepresented in the current reserve system. The creation of the proposed areas would substantially increase the protection of mid and high elevation lands. The largest gap in the protected lands network would be low elevation, level, coastal lands.

  5. A roadmap for successful applications of clinical proteomics.

    PubMed

    Ioannidis, John P A

    2011-06-01

    Despite over 30,000 publications on proteomics in the last decade, and the accumulation of extensive interesting information on the human proteome in diverse observations, the clinical translation of proteomics to-date has had major setbacks. I review here a roadmap for improving the success rate of clinical proteomics. The roadmap includes steps for improvements that need to be made in analytical tools, discovery, validation, clinical application, and post-clinical application appraisal. It is likely that most if not all of the components that are necessary for clinical success are either readily available, or should be possible to put in place with more rigorous research standards and concerted efforts of the research community, clinicians, and health agencies. Enthusiasm for the clinical impact of proteomics may need to be tempered currently until robust evidence can be obtained, but some clinical successes should eventually be feasible. PMID:21523915

  6. Pharmacological treatment of Alzheimer's dementia: state of the art and current dilemmas.

    PubMed

    Omerovic, Muamer; Hampel, Harald; Teipel, Stefan J; Buerger, Katharina

    2008-01-01

    Alzheimer's disease (AD) is one of the most frequent disorders of the central nervous system characterised by a progressive cognitive decline. The demographic changes of our aging population lead to increased numbers of patients and a need of early diagnosis and treatment of cognitive and behavioural symptoms of AD. Drugs are available for symptomatic treatment of AD. The pharmacological treatment of behavioural disturbances experienced dynamic changes in the last years. In this paper, we present the current state and future perspectives in the treatment of AD. Furthermore, we discuss current difficulties regarding AD treatment by looking for explanations for a still unsatisfying rate of state-of-the-art treatment of AD-patients. PMID:17886162

  7. HepatoProteomics: Applying Proteomic Technologies to the Study of Liver Function and Disease

    SciTech Connect

    Diamond, Deborah L.; Proll, Sean; Jacobs, Jon M.; Chan, Eric Y.; Camp, David G.; Smith, Richard D.; Katze, Michael G.

    2006-08-01

    The wealth of human genome sequence information now available, coupled with technological advances in robotics, nanotechnology, mass spectrometry, and information systems, has given rise to a method of scientific inquiry known as functional genomics. By using these technologies to survey gene expression and protein production on a near global scale, the goal of functional genomics is to assign biological function to genes with currently unknown roles in physiology. This approach carries particular appeal in disease research, where it can uncover the function of previously unknown genes and molecular pathways that are directly involved in disease progression. With this knowledge may come improved diagnostic techniques, prognostic capabilities, and novel therapeutic approaches. In this regard, the continuing evolution of proteomic technologies has resulted in an increasingly greater impact of proteome studies in many areas of research and hepatology is no exception. Our laboratory has been extremely active in this area, applying both genomic and proteomic technologies to the analysis of virus-host interactions in several systems, including the study of hepatitis C virus (HCV) infection and HCV-associated liver disease. Since proteomic technologies are foreign to many hepatologists (and to almost everyone else), this article will provide an overview of proteomic methods and technologies and describe how they're being used to study liver function and disease. We use our studies of HCV infection and HCV-associated liver disease to present an operational framework for performing high throughput proteome analysis and extracting biologically meaningful information.

  8. Role of the proteome in phytohormonal signaling.

    PubMed

    Černý, Martin; Novák, Jan; Habánová, Hana; Cerna, Hana; Brzobohatý, Břetislav

    2016-08-01

    Phytohormones are orchestrators of plant growth and development. A lot of time and effort has been invested in attempting to comprehend their complex signaling pathways but despite success in elucidating some key components, molecular mechanisms in the transduction pathways are far from being resolved. The last decade has seen a boom in the analysis of phytohormone-responsive proteins. Abscisic acid, auxin, brassinosteroids, cytokinin, ethylene, gibberellins, nitric oxide, oxylipins, strigolactones, salicylic acid--all have been analyzed to various degrees. For this review, we collected data from proteome-wide analyses resulting in a list of over 2000 annotated proteins from Arabidopsis proteomics and nearly 500 manually filtered protein families merged from all the data available from different species. We present the currently accepted model of phytohormone signaling, highlight the contributions made by proteomic-based research and describe the key nodes in phytohormone signaling networks, as revealed by proteome analysis. These include ubiquitination and proteasome mediated degradation, calcium ion signaling, redox homeostasis, and phosphoproteome dynamics. Finally, we discuss potential pitfalls and future perspectives in the field. This article is part of a Special Issue entitled: Plant Proteomics--a bridge between fundamental processes and crop production, edited by Dr. Hans-Peter Mock. PMID:26721743

  9. Pathway and network analysis in proteomics.

    PubMed

    Wu, Xiaogang; Hasan, Mohammad Al; Chen, Jake Yue

    2014-12-01

    Proteomics is inherently a systems science that studies not only measured protein and their expressions in a cell, but also the interplay of proteins, protein complexes, signaling pathways, and network modules. There is a rapid accumulation of Proteomics data in recent years. However, Proteomics data are highly variable, with results sensitive to data preparation methods, sample condition, instrument types, and analytical methods. To address the challenge in Proteomics data analysis, we review current tools being developed to incorporate biological function and network topological information. We categorize these tools into four types: tools with basic functional information and little topological features (e.g., GO category analysis), tools with rich functional information and little topological features (e.g., GSEA), tools with basic functional information and rich topological features (e.g., Cytoscape), and tools with rich functional information and rich topological features (e.g., PathwayExpress). We first review the potential application of these tools to Proteomics; then we review tools that can achieve automated learning of pathway modules and features, and tools that help perform integrated network visual analytics. PMID:24911777

  10. The Current State of Vaccine Development for Ocular HSV-1 Infection

    PubMed Central

    Royer, DJ; Cohen, A; Carr, DJJ

    2015-01-01

    Summary HSV-1 continues to be the leading cause of infectious corneal blindness. Clinical trials for vaccines against genital HSV infection have been ongoing for more than three decades. Despite this, no approved vaccine exists, and no formal clinical trials have evaluated the impact of HSV vaccines on eye health. We review here the current state of development for an efficacious HSV-1 vaccine and call for involvement of ophthalmologists and vision researchers. PMID:25983856

  11. Spatially-Resolved Beam Current and Charge-State Distributions for the NEXT Ion Engine

    NASA Technical Reports Server (NTRS)

    Pollard, James E.; Diamant, Kevin D.; Crofton, Mark W.; Patterson, Michael J.; Soulas, George C.

    2010-01-01

    Plume characterization tests with the 36-cm NEXT ion engine are being performed at The Aerospace Corporation using engineering-model and prototype-model thrusters. We have examined the beam current density and xenon charge-state distribution as functions of position on the accel grid. To measure the current density ratio j++/j+, a collimated Eprobe was rotated through the plume with the probe oriented normal to the accel electrode surface at a distance of 82 cm. The beam current density jb versus radial position was measured with a miniature planar probe at 3 cm from the accel. Combining the j++/j+ and jb data yielded the ratio of total Xe+2 current to total Xe+1 current (J++/J+) at forty operating points in the standard throttle table. The production of Xe+2 and Xe+3 was measured as a function of propellant utilization to support performance and lifetime predictions for an extended throttle table. The angular dependence of jb was measured at intermediate and far-field distances to assist with plume modeling and to evaluate the thrust loss due to beam divergence. Thrust correction factors were derived from the total doubles-to-singles current ratio and from the far-field divergence data

  12. GENOMIC AND PROTEOMIC TECHNIQUES APPLIED TO REPRODUCTIVE BIOLOGY

    EPA Science Inventory

    Genomic and proteomic techniques applied to reproductive biology
    John C. Rockett
    Reproductive Toxicology Division, National Health and Environmental Effects Research Laboratory, Office of Research and Development, United States Environmental Protection Agency, Research Tria...

  13. Human pathogenic streptococcal proteomics and vaccine development.

    PubMed

    Cole, Jason N; Henningham, Anna; Gillen, Christine M; Ramachandran, Vidiya; Walker, Mark J

    2008-03-01

    Gram-positive streptococci are non-motile, chain-forming bacteria commonly found in the normal oral and bowel flora of warm-blooded animals. Over the past decade, a proteomic approach combining 2-DE and MS has been used to systematically map the cellular, surface-associated and secreted proteins of human pathogenic streptococcal species. The public availability of complete streptococcal genomic sequences and the amalgamation of proteomic, genomic and bioinformatic technologies have recently facilitated the identification of novel streptococcal vaccine candidate antigens and therapeutic agents. The objective of this review is to examine the constituents of the streptococcal cell wall and secreted proteome, the mechanisms of transport of surface and secreted proteins, and describe the current methodologies employed for the identification of novel surface-displayed proteins and potential vaccine antigens. PMID:21136841

  14. A comprehensive compilation of SUMO proteomics.

    PubMed

    Hendriks, Ivo A; Vertegaal, Alfred C O

    2016-09-01

    Small ubiquitin-like modifiers (SUMOs) are essential for the regulation of several cellular processes and are potential therapeutic targets owing to their involvement in diseases such as cancer and Alzheimer disease. In the past decade, we have witnessed a rapid expansion of proteomic approaches for identifying sumoylated proteins, with recent advances in detecting site-specific sumoylation. In this Analysis, we combined all human SUMO proteomics data currently available into one cohesive database. We provide proteomic evidence for sumoylation of 3,617 proteins at 7,327 sumoylation sites, and insight into SUMO group modification by clustering the sumoylated proteins into functional networks. The data support sumoylation being a frequent protein modification (on par with other major protein modifications) with multiple nuclear functions, including in transcription, mRNA processing, DNA replication and the DNA-damage response. PMID:27435506

  15. Trans-Proteomic Pipeline, a standardized data processing pipeline for large-scale reproducible proteomics informatics

    PubMed Central

    Deutsch, Eric W.; Mendoza, Luis; Shteynberg, David; Slagel, Joseph; Sun, Zhi; Moritz, Robert L.

    2015-01-01

    Democratization of genomics technologies has enabled the rapid determination of genotypes. More recently the democratization of comprehensive proteomics technologies is enabling the determination of the cellular phenotype and the molecular events that define its dynamic state. Core proteomic technologies include mass spectrometry to define protein sequence, protein:protein interactions, and protein post-translational modifications. Key enabling technologies for proteomics are bioinformatic pipelines to identify, quantitate, and summarize these events. The Trans-Proteomics Pipeline (TPP) is a robust open-source standardized data processing pipeline for large-scale reproducible quantitative mass spectrometry proteomics. It supports all major operating systems and instrument vendors via open data formats. Here we provide a review of the overall proteomics workflow supported by the TPP, its major tools, and how it can be used in its various modes from desktop to cloud computing. We describe new features for the TPP, including data visualization functionality. We conclude by describing some common perils that affect the analysis of tandem mass spectrometry datasets, as well as some major upcoming features. PMID:25631240

  16. Trans-Proteomic Pipeline, a standardized data processing pipeline for large-scale reproducible proteomics informatics.

    PubMed

    Deutsch, Eric W; Mendoza, Luis; Shteynberg, David; Slagel, Joseph; Sun, Zhi; Moritz, Robert L

    2015-08-01

    Democratization of genomics technologies has enabled the rapid determination of genotypes. More recently the democratization of comprehensive proteomics technologies is enabling the determination of the cellular phenotype and the molecular events that define its dynamic state. Core proteomic technologies include MS to define protein sequence, protein:protein interactions, and protein PTMs. Key enabling technologies for proteomics are bioinformatic pipelines to identify, quantitate, and summarize these events. The Trans-Proteomics Pipeline (TPP) is a robust open-source standardized data processing pipeline for large-scale reproducible quantitative MS proteomics. It supports all major operating systems and instrument vendors via open data formats. Here, we provide a review of the overall proteomics workflow supported by the TPP, its major tools, and how it can be used in its various modes from desktop to cloud computing. We describe new features for the TPP, including data visualization functionality. We conclude by describing some common perils that affect the analysis of MS/MS datasets, as well as some major upcoming features. PMID:25631240

  17. Current oscillation of snake states in graphene p-n junction

    NASA Astrophysics Data System (ADS)

    Chen, Jiang-chai; Xie, X. C.; Sun, Qing-feng

    2012-07-01

    Snake states in a six-terminal graphene p-n junction are investigated under a perpendicular magnetic field. The current oscillation with varying magnetic field appears due to the presence of snake states at the p-n interface. At a fixed magnetic field, the periodic properties of currents with respect to the geometric structures, such as the graphene ribbon width and the location of the incident terminal, are also shown. We extract the values of the width and the location corresponding to the maximums of the current and plot them versus their sequence number. They form a straight line, which shows that the oscillation is periodic. The periods decrease with increasing magnetic field. The order of magnitude of periods and their tendencies with varying a magnetic field are consistent with those predicted from semiclassical motions. Finally, for a smooth potential, the snake states still survive and the oscillation phase and the oscillation period with respect to the location of the incident terminal are almost unchanged, but the period with respect to the width of the ribbon is reduced.

  18. Proteome Characterization Centers - TCGA

    Cancer.gov

    The centers, a component of NCI’s Clinical Proteomic Tumor Analysis Consortium, will analyze a subset of TCGA samples to define proteins translated from cancer genomes and their related biological processes.

  19. The CPTAC Data Portal: A Resource for Cancer Proteomics Research.

    PubMed

    Edwards, Nathan J; Oberti, Mauricio; Thangudu, Ratna R; Cai, Shuang; McGarvey, Peter B; Jacob, Shine; Madhavan, Subha; Ketchum, Karen A

    2015-06-01

    The Clinical Proteomic Tumor Analysis Consortium (CPTAC), under the auspices of the National Cancer Institute's Office of Cancer Clinical Proteomics Research, is a comprehensive and coordinated effort to accelerate the understanding of the molecular basis of cancer through the application of proteomic technologies and workflows to clinical tumor samples with characterized genomic and transcript profiles. The consortium analyzes cancer biospecimens using mass spectrometry, identifying and quantifying the constituent proteins and characterizing each tumor sample's proteome. Mass spectrometry enables highly specific identification of proteins and their isoforms, accurate relative quantitation of protein abundance in contrasting biospecimens, and localization of post-translational protein modifications, such as phosphorylation, on a protein's sequence. The combination of proteomics, transcriptomics, and genomics data from the same clinical tumor samples provides an unprecedented opportunity for tumor proteogenomics. The CPTAC Data Portal is the centralized data repository for the dissemination of proteomic data collected by Proteome Characterization Centers (PCCs) in the consortium. The portal currently hosts 6.3 TB of data and includes proteomic investigations of breast, colorectal, and ovarian tumor tissues from The Cancer Genome Atlas (TCGA). The data collected by the consortium is made freely available to the public through the data portal. PMID:25873244

  20. The Escherichia coli Proteome: Past, Present, and Future Prospects†

    PubMed Central

    Han, Mee-Jung; Lee, Sang Yup

    2006-01-01

    Proteomics has emerged as an indispensable methodology for large-scale protein analysis in functional genomics. The Escherichia coli proteome has been extensively studied and is well defined in terms of biochemical, biological, and biotechnological data. Even before the entire E. coli proteome was fully elucidated, the largest available data set had been integrated to decipher regulatory circuits and metabolic pathways, providing valuable insights into global cellular physiology and the development of metabolic and cellular engineering strategies. With the recent advent of advanced proteomic technologies, the E. coli proteome has been used for the validation of new technologies and methodologies such as sample prefractionation, protein enrichment, two-dimensional gel electrophoresis, protein detection, mass spectrometry (MS), combinatorial assays with n-dimensional chromatographies and MS, and image analysis software. These important technologies will not only provide a great amount of additional information on the E. coli proteome but also synergistically contribute to other proteomic studies. Here, we review the past development and current status of E. coli proteome research in terms of its biological, biotechnological, and methodological significance and suggest future prospects. PMID:16760308

  1. The plasma environment, charge state, and currents of Saturn's C and D rings

    NASA Technical Reports Server (NTRS)

    Wilson, G. R.

    1991-01-01

    The charge state and associated currents of Saturn's C an D rings are studied by modeling the flow of ionospheric plasma from the mid- to low-latitude ionosphere to the vicinity of the rings. It is found that the plasma density near the C and D rings, at a given radial location, will experience a one to two order of magnitude diurnal variation. The surface charge density (SCD) of these rings can show significant radial and azimuthal variations due mainly to variation in the plasma density. The SCD also depends on structural features of the rings such as thickness and the nature of the particle size distribution. The associated azimuthal currents carried by these rings also show large diurnal variations resulting in field-aligned currents which close in the ionosphere. The resulting ionospheric electric field will probably not produce a significant amount of plasma convection in the topside ionosphere and inner plasmasphere.

  2. Macroscopic quantum effects in the zero voltage state of the current biased Josephson junction

    SciTech Connect

    Clarke, J.; Devoret, M.H.; Martinis, J.; Esteve, D.

    1985-05-01

    When a weak microwave current is applied to a current-biased Josephson tunnel junction in the thermal limit the escape rate from the zero voltage state is enhanced when the microwave frequency is near the plasma frequency of the junction. The resonance curve is markedly asymmetric because of the anharmonic properties of the potential well: this behavior is well explained by a computer simulation using a resistively shunted junction model. This phenomenon of resonant activation enables one to make in situ measurements of the capacitance and resistance shunting the junction, including contributions from the complex impedance presented by the current leads. For the relatively large area junctions studied in these experiments, the external capacitive loading was relatively unimportant, but the damping was entirely dominated by the external resistance.

  3. A review of the current state of knowledge of fossil Mantispidae (Insecta: Neuroptera).

    PubMed

    Jepson, James E

    2015-01-01

    There are 32 individual specimens of Mantispidae (Insecta: Neuroptera) currently recorded from the fossil record, the oldest of which dates back to the Lower Jurassic. These include 19 described species (in 16 genera), 1 specimen described to genus level and 9 unnamed specimens The specimens have been assigned to the extant subfamilies Drepanicinae (4), Mantispinae (10), Symphrasinae (1), and the extinct subfamily Mesomantispinae (16), with one incertae sedis within Mantispidae. There are currently no known fossil representatives of the subfamily Calomantispinae. Mesithoninae has been removed from Mantispidae and placed back within Berothidae. The species Mesithone carnaria and M. monstruosa, however, are true mantispids and have been removed from Mesithone and placed within a new genus Karataumantispa gen. nov. in the subfamily Mesomantispinae. The current state of knowledge of the fossil record of Mantispidae is reviewed and a key to the genera of Mesomantispinae is provided. PMID:26249453

  4. Thermally Stimulated Discharge Current Analysis of Polymeric Solid-State Ionic Conductors

    NASA Astrophysics Data System (ADS)

    Xu, Haisheng; Gu, Qingchao; Fan, Maosen; Yang, Changzheng

    1997-06-01

    Thermally Stimulated Discharge Current (TSDC) analysis was used to study the electrical properties of two systems of polymeric solid-state ionic conductors. One system consisted of LiClO4 doped polyethylene glycol polyurethaneureas (PEUU) characterized by bi-ionic conduction and the other system was based on a sulfonated polyethylene oxide polyurethane ionomer (SPUI) characterized by a single-ion transport mechanism. TSDC spectra of the PEUU as well as SPUI matrices showed four peaks (, , , and ). These peaks are found to be related to the local motion of polyether soft segments, glass transition, Maxwell-Wagner-Sillars interfacial polarization and transport of charged ionic species, respectively. The discharge currents without polarization varying with temperature for both, the PEUU-LiClO4 complex and SPUI, are also measured. These curves of discharge current show only one peak which is attributed to transport of charged ionic species. The temperature range in which the discharge current exhibits a steep increase is consistent with the temperature range in which a turning point appears on the plot of lg i versus 1000/T obtained by ac impedance analysis. The experimental results demonstrate that the TSDC analysis is a valuable tool for studying polymeric solid-state ionic conductors.

  5. Proteomics in evolutionary ecology.

    PubMed

    Baer, B; Millar, A H

    2016-03-01

    Evolutionary ecologists are traditionally gene-focused, as genes propagate phenotypic traits across generations and mutations and recombination in the DNA generate genetic diversity required for evolutionary processes. As a consequence, the inheritance of changed DNA provides a molecular explanation for the functional changes associated with natural selection. A direct focus on proteins on the other hand, the actual molecular agents responsible for the expression of a phenotypic trait, receives far less interest from ecologists and evolutionary biologists. This is partially due to the central dogma of molecular biology that appears to define proteins as the 'dead-end of molecular information flow' as well as technical limitations in identifying and studying proteins and their diversity in the field and in many of the more exotic genera often favored in ecological studies. Here we provide an overview of a newly forming field of research that we refer to as 'Evolutionary Proteomics'. We point out that the origins of cellular function are related to the properties of polypeptide and RNA and their interactions with the environment, rather than DNA descent, and that the critical role of horizontal gene transfer in evolution is more about coopting new proteins to impact cellular processes than it is about modifying gene function. Furthermore, post-transcriptional and post-translational processes generate a remarkable diversity of mature proteins from a single gene, and the properties of these mature proteins can also influence inheritance through genetic and perhaps epigenetic mechanisms. The influence of post-transcriptional diversification on evolutionary processes could provide a novel mechanistic underpinning for elements of rapid, directed evolutionary changes and adaptations as observed for a variety of evolutionary processes. Modern state-of the art technologies based on mass spectrometry are now available to identify and quantify peptides, proteins, protein

  6. Proteomics Research in Schizophrenia

    PubMed Central

    Davalieva, Katarina; Maleva Kostovska, Ivana; Dwork, Andrew J.

    2016-01-01

    Despite intense scientific efforts, the neuropathology and pathophysiology of schizophrenia are poorly understood. Proteomic studies, by testing large numbers of proteins for associations with disease, may contribute to the understanding of the molecular mechanisms of schizophrenia. They may also indicate the types and locations of cells most likely to harbor pathological alterations. Investigations using proteomic approaches have already provided much information on quantitative and qualitative protein patterns in postmortem brain tissue, peripheral tissues and body fluids. Different proteomic technologies such as 2-D PAGE, 2-D DIGE, SELDI-TOF, shotgun proteomics with label-based (ICAT), and label-free (MSE) quantification have been applied to the study of schizophrenia for the past 15 years. This review summarizes the results, mostly from brain but also from other tissues and bodily fluids, of proteomics studies in schizophrenia. Emphasis is given to proteomics platforms, varying sources of material, proposed candidate biomarkers emerging from comparative proteomics studies, and the specificity of the putative markers in terms of other mental illnesses. We also compare proteins altered in schizophrenia with reports of protein or mRNA sequences that are relatively enriched in specific cell types. While proteomic studies of schizophrenia find abnormalities in the expression of many proteins that are not cell type-specific, there appears to be a disproportionate representation of proteins whose synthesis and localization are highly enriched in one or more brain cell type compared with other types of brain cells. Two of the three proteins most commonly altered in schizophrenia are aldolase C and glial fibrillary acidic protein, astrocytic proteins with entirely different functions, but the studies are approximately evenly divided with regard to the direction of the differences and the concordance or discordance between the two proteins. Alterations of common myelin

  7. Proteomics Research in Schizophrenia.

    PubMed

    Davalieva, Katarina; Maleva Kostovska, Ivana; Dwork, Andrew J

    2016-01-01

    Despite intense scientific efforts, the neuropathology and pathophysiology of schizophrenia are poorly understood. Proteomic studies, by testing large numbers of proteins for associations with disease, may contribute to the understanding of the molecular mechanisms of schizophrenia. They may also indicate the types and locations of cells most likely to harbor pathological alterations. Investigations using proteomic approaches have already provided much information on quantitative and qualitative protein patterns in postmortem brain tissue, peripheral tissues and body fluids. Different proteomic technologies such as 2-D PAGE, 2-D DIGE, SELDI-TOF, shotgun proteomics with label-based (ICAT), and label-free (MS(E)) quantification have been applied to the study of schizophrenia for the past 15 years. This review summarizes the results, mostly from brain but also from other tissues and bodily fluids, of proteomics studies in schizophrenia. Emphasis is given to proteomics platforms, varying sources of material, proposed candidate biomarkers emerging from comparative proteomics studies, and the specificity of the putative markers in terms of other mental illnesses. We also compare proteins altered in schizophrenia with reports of protein or mRNA sequences that are relatively enriched in specific cell types. While proteomic studies of schizophrenia find abnormalities in the expression of many proteins that are not cell type-specific, there appears to be a disproportionate representation of proteins whose synthesis and localization are highly enriched in one or more brain cell type compared with other types of brain cells. Two of the three proteins most commonly altered in schizophrenia are aldolase C and glial fibrillary acidic protein, astrocytic proteins with entirely different functions, but the studies are approximately evenly divided with regard to the direction of the differences and the concordance or discordance between the two proteins. Alterations of common myelin

  8. System and method for generating steady state confining current for a toroidal plasma fusion reactor

    DOEpatents

    Fisch, Nathaniel J.

    1981-01-01

    A system for generating steady state confining current for a toroidal plasma fusion reactor providing steady-state generation of the thermonuclear power. A dense, hot toroidal plasma is initially prepared with a confining magnetic field with toroidal and poloidal components. Continuous wave RF energy is injected into said plasma to establish a spectrum of traveling waves in the plasma, where the traveling waves have momentum components substantially either all parallel, or all anti-parallel to the confining magnetic field. The injected RF energy is phased to couple to said traveling waves with both a phase velocity component and a wave momentum component in the direction of the plasma traveling wave components. The injected RF energy has a predetermined spectrum selected so that said traveling waves couple to plasma electrons having velocities in a predetermined range .DELTA.. The velocities in the range are substantially greater than the thermal electron velocity of the plasma. In addition, the range is sufficiently broad to produce a raised plateau having width .DELTA. in the plasma electron velocity distribution so that the plateau electrons provide steady-state current to generate a poloidal magnetic field component sufficient for confining the plasma. In steady state operation of the fusion reactor, the fusion power density in the plasma exceeds the power dissipated in the plasma.

  9. System and method for generating steady state confining current for a toroidal plasma fusion reactor

    DOEpatents

    Bers, Abraham

    1981-01-01

    A system for generating steady state confining current for a toroidal plasma fusion reactor providing steady-state generation of the thermonuclear power. A dense, hot toroidal plasma is initially prepared with a confining magnetic field with toroidal and poloidal components. Continuous wave RF energy is injected into said plasma to estalish a spectrum of traveling waves in the plasma, where the traveling waves have momentum components substantially either all parallel, or all anti-parallel to the confining magnetic field. The injected RF energy is phased to couple to said traveling waves with both a phase velocity component and a wave momentum component in the direction of the plasma traveling wave components. The injected RF energy has a predetermined spectrum selected so that said traveling waves couple to plasma electrons having velocities in a predetermined range .DELTA.. The velocities in the range are substantially greater than the thermal electron velocity of the plasma. In addition, the range is sufficiently broad to produce a raised plateau having width .DELTA. in the plasma electron velocity distribution so that the plateau electrons provide steady-state current to generate a poloidal magnetic field component sufficient for confining the plasma. In steady state operation of the fusion reactor, the fusion power density in the plasma exceeds the power dissipated inthe plasma.

  10. Integrated modelling of DEMO-FNS current ramp-up scenario and steady-state regime

    NASA Astrophysics Data System (ADS)

    Dnestrovskij, A. Yu.; Kuteev, B. V.; Bykov, A. S.; Ivanov, A. A.; Lukash, V. E.; Medvedev, S. Yu.; Sergeev, V. Yu.; Sychugov, D. Yu.; Khayrutdinov, R. R.

    2015-06-01

    An approach to the integrated modelling of plasma regimes in the projected neutron source DEMO-FNS based on different codes is developed. The consistency check of the steady-state regime is carried out, namely, the possibility of the plasma current ramp-up, acceptance of growth rates of MHD modes in the steady-state regime, heat loads to the wall and divertor plates and neutron yield value. The following codes are employed for the integrated modelling. ASTRA transport code for calculation of plasma parameters in the steady-state regime, NUBEAM Monte Carlo code for NBI incorporated into the ASTRA code, DINA free boundary equilibrium and evolution code, SPIDER free boundary equilibrium and equilibrium reconstruction code, KINX ideal MHD stability code, TOKSTAB rigid shift vertical stability code, edge and divertor plasma B2SOLPS5.2 code and Semi-analytic Hybrid Model (SHM) code for self-consistent description of the core, edge and divertor plasmas based on the experimental scaling laws. The consistent steady-state regime for the DEMO-FNS plasma and the plasma current ramp-up scenario are developed using the integrated modelling approach. Passive copper coils are suggested to reduce the plasma vertical instability growth rate to below ˜30 s-1.The outer divertor operation in the ‘high-recycling’ regime is numerically demonstrated with a maximal heat flux density of 7-9 MW m-2 that is technically acceptable.

  11. Proteomic landscape in Central and Eastern Europe: the 9th Central and Eastern European Proteomic Conference, Poznań, Poland.

    PubMed

    Gadher, Suresh Jivan; Marczak, Łukasz; Łuczak, Magdalena; Stobiecki, Maciej; Widlak, Piotr; Kovarova, Hana

    2016-01-01

    Every year since 2007, the Central and Eastern European Proteomic Conference (CEEPC) has excelled in representing state-of-the-art proteomics in and around Central and Eastern Europe, and linking it to international institutions worldwide. Its mission remains to contribute to all approaches of proteomics including traditional and often-revisited methodologies as well as the latest technological achievements in clinical, quantitative and structural proteomics with a view to systems biology of a variety of processes. The 9th CEEPC was held from June 15th to 18th, 2015, at the Institute of Bioorganic Chemistry, Polish Academy of Sciences in Poznań, Poland. The scientific program stimulated exchange of proteomic knowledge whilst the spectacular venue of the conference allowed participants to enjoy the cobblestoned historical city of Poznań. PMID:26558656

  12. Collaborations in Proteomics Research - Office of Cancer Clinical Proteomics Research

    Cancer.gov

    The National Cancer Institute (NCI), through the Office of Cancer Clinical Proteomics Research (OCCPR), has signed two Memorandums of Understanding (MOUs) in the sharing of proteomics reagents and protocols

  13. The current state-of-the-art of spinal cord imaging: Applications

    PubMed Central

    Wheeler-Kingshott, C.A.; Stroman, P.W.; Schwab, J.M.; Bacon, M.; Bosma, R.; Brooks, J.; Cadotte, D.W.; Carlstedt, T.; Ciccarelli, O.; Cohen-Adad, J.; Curt, A.; Evangelou, N.; Fehlings, M.G.; Filippi, M.; Kelley, B.J.; Kollias, S.; Mackay, A.; Porro, C.A.; Smith, S.; Strittmatter, S.M.; Summers, P.; Thompson, A.J.; Tracey, I.

    2015-01-01

    A first-ever spinal cord imaging meeting was sponsored by the International Spinal Research Trust and the Wings for Life Foundation with the aim of identifying the current state-of-the-art of spinal cord imaging, the current greatest challenges, and greatest needs for future development. This meeting was attended by a small group of invited experts spanning all aspects of spinal cord imaging from basic research to clinical practice. The greatest current challenges for spinal cord imaging were identified as arising from the imaging environment itself; difficult imaging environment created by the bone surrounding the spinal canal, physiological motion of the cord and adjacent tissues, and small crosssectional dimensions of the spinal cord, exacerbated by metallic implants often present in injured patients. Challenges were also identified as a result of a lack of “critical mass” of researchers taking on the development of spinal cord imaging, affecting both the rate of progress in the field, and the demand for equipment and software to manufacturers to produce the necessary tools. Here we define the current state-of-the-art of spinal cord imaging, discuss the underlying theory and challenges, and present the evidence for the current and potential power of these methods. In two review papers (part I and part II), we propose that the challenges can be overcome with advances in methods, improving availability and effectiveness of methods, and linking existing researchers to create the necessary scientific and clinical network to advance the rate of progress and impact of the research. PMID:23859923

  14. Current state and perspectives of producing biodiesel‐like compounds by biotechnology

    PubMed Central

    Uthoff, Stefan; Bröker, Daniel; Steinbüchel, Alexander

    2009-01-01

    Summary The global demand for crude oil is expected to continue to rise in future while simultaneously oil production is currently reaching its peak. Subsequently, rising oil prices and their negative impacts on economy, together with an increased environmental awareness of our society, directed the focus also on the biotechnological production of fuels. Although a wide variety of such fuels has been suggested, only the production of ethanol and biodiesel has reached a certain economic feasibility and volume, yet. This review focuses on the current state and perspectives of biotechnological production of biodiesel‐like compounds. At present by far most of the produced biodiesel is obtained by chemical transesterification reactions, which cannot meet the demands of a totally ‘green’ fuel production. Therefore, also several biotechnological biodiesel production processes are currently being developed. Biotechnological production can be achieved by purified enzymes in the soluble state, which requires cost‐intensive protein preparation. Alternatively, enzymes could be immobilized on an appropriate matrix, enabling a reuse of the enzyme, although the formation of by‐products may provide difficulties to maintain the enzyme activity. Processes in presence of organic solvents like t‐butanol have been developed, which enhance by‐product solubility and therefore prevent loss of enzyme activity. As another approach the application of whole‐cell catalysis for the production of fatty acid ethyl esters, which is also referred to as ‘microdiesel’, by recombinant microorganisms has recently been suggested. PMID:21255288

  15. Is current consumption excessive? A general framework and some indications for the United States.

    PubMed

    Ehrlich, Paul R; Goulder, Lawrence H

    2007-10-01

    Many prior studies have explored the implications of human population growth and environmentally problematic technologies for biodiversity loss and other forms of environmental degradation. Relatively few, however, have examined the impacts of the level and composition of consumption. We offer a framework that shows how the level and composition of a society's total consumption relate to the uses of various forms of capital and to the sustainability of natural resources and human well-being. We relate the framework to two main approaches-top-down macro studies and bottom-up computer models-for measuring whether overall consumption in the United States satisfies a sustainability requirement. Existing top-down studies have shortcomings that bias their results toward optimism, and current computer simulation models, although strong on revealing biophysical outcomes, are limited in their ability to evaluate impacts on human well-being. Although some ambiguities arise in determining whether overall consumption in the United States is excessive, our conclusions regarding the composition of U.S. consumption are unambiguous. Distorted consumption patterns and associated production methods lead to excessively rapid natural resource depletion; greater conservation would yield gains to current and future generations that more than compensate for the sacrifices involved. Public policies that deal with the composition problem not only would help conserve natural resources and improve current welfare but also would reduce the costs of meeting the goal of sustainability. PMID:17883480

  16. Description of plasma focus current sheath as the Turner relaxed state of a Hall magnetofluid

    SciTech Connect

    Auluck, S. K. H.

    2009-12-15

    The central mystery of plasma focus research is the two orders-of-magnitude-higher-than-thermal fusion reaction rate and the fact that both the space-resolved neutron spectra and space-resolved reaction proton spectra show features which can be ascribed only to a rotational motion of the center-of-mass of the reacting deuteron population. It has been suggested earlier [S. K. H. Auluck, IEEE Trans. Plasma Sci. 25, 37 (1997)] that this and other experimental observations can be consistently explained in terms of a hypothesis involving rotation of the current carrying plasma annulus behind the imploding gas-dynamic shock. Such rotation (more generally, mass flow) is an in-built feature of relaxed state of a two-fluid plasma [R. N. Sudan, Phys. Rev. Lett. 42, 1277 (1979)]. Relaxation in the 'Hall magnetofluid' approximation, in which the generalized Ohm's law includes the Hall effect term and the magnetic convection term but omits the contributions to the electric field from resistive dissipation, electron pressure gradient, thermoelectric effect, electron inertia, etc., has been extensively studied by many authors. In the present paper, Turner's [IEEE Trans. Plasma Sci. PS-14, 849 (1986)] degenerate solution for the relaxed state of the Hall magnetohydrodynamic plasma has been adapted to the case of an infinitely long annular current carrying plasma, a tractable idealization of the current sheath of a plasma focus. The resulting model is consistent with experimental values of ion kinetic energy and observation of predominantly radially directed neutron emission in good shots.

  17. Proteomics: Challenges, Techniques and Possibilities to Overcome Biological Sample Complexity

    PubMed Central

    Chandramouli, Kondethimmanahalli; Qian, Pei-Yuan

    2009-01-01

    Proteomics is the large-scale study of the structure and function of proteins in complex biological sample. Such an approach has the potential value to understand the complex nature of the organism. Current proteomic tools allow large-scale, high-throughput analyses for the detection, identification, and functional investigation of proteome. Advances in protein fractionation and labeling techniques have improved protein identification to include the least abundant proteins. In addition, proteomics has been complemented by the analysis of posttranslational modifications and techniques for the quantitative comparison of different proteomes. However, the major limitation of proteomic investigations remains the complexity of biological structures and physiological processes, rendering the path of exploration paved with various difficulties and pitfalls. The quantity of data that is acquired with new techniques places new challenges on data processing and analysis. This article provides a brief overview of currently available proteomic techniques and their applications, followed by detailed description of advantages and technical challenges. Some solutions to circumvent technical difficulties are proposed. PMID:20948568

  18. Proteomics analysis of human oligodendroglioma proteome.

    PubMed

    Khaghani-Razi-Abad, Solmaz; Hashemi, Mehrdad; Pooladi, Mehdi; Entezari, Maliheh; Kazemi, Elham

    2015-09-10

    Proteomics analyses enable the identification and quantitation of proteins. From a purely clinical perspective, the application of proteomics based on innovations, may greatly affect the future management of malignant brain tumors. This optimism is based on four main reasons: diagnosis, prognosis, selection of targeted therapy based on molecular profile of the brain tumor and monitoring therapeutic response, or resistance. We extracted the proteins of tumor and normal brain tissues, and then evaluated the protein purity by Bradford test. In this study, we separated the proteins by two-dimensional (2DG) gel electrophoresis methods. Then spots were analyzed, compared using statistical data and specific software and were identified by pH isoelectric, molecular weights and data banks. The protein profiles were determined using 2D gel electrophoresis and MALDI TOF/TOF mass spectrometry approaches. Simple statistical tests were used to establish a putative hierarchy in which the change in protein level was ranked according to a cut-off point with p<0.05. The 2D gel showed a total of 1328 spots among which 157 spots were under-expressed and 276 spots were overexpressed. Most proteins are subjects to post-translational modifications, where amino acid residues may be chemically modified or conjugated by small proteins like ubiquitin. Proteomics is a powerful way to identifying multiple proteins which are altered following a neuropharmacological intervention in a CNS disease. PMID:26002447

  19. Assessment of Energy Production Potential from Ocean Currents along the United States Coastline

    SciTech Connect

    Haas, Kevin

    2013-09-15

    Increasing energy consumption and depleting reserves of fossil fuels have resulted in growing interest in alternative renewable energy from the ocean. Ocean currents are an alternative source of clean energy due to their inherent reliability, persistence and sustainability. General ocean circulations exist in the form of large rotating ocean gyres, and feature extremely rapid current flow in the western boundaries due to the Coriolis Effect. The Gulf Stream system is formed by the western boundary current of the North Atlantic Ocean that flows along the east coastline of the United States, and therefore is of particular interest as a potential energy resource for the United States. This project created a national database of ocean current energy resources to help advance awareness and market penetration in ocean current energy resource assessment. The database, consisting of joint velocity magnitude and direction probability histograms, was created from data created by seven years of numerical model simulations. The accuracy of the database was evaluated by ORNL?s independent validation effort documented in a separate report. Estimates of the total theoretical power resource contained in the ocean currents were calculated utilizing two separate approaches. Firstly, the theoretical energy balance in the Gulf Stream system was examined using the two-dimensional ocean circulation equations based on the assumptions of the Stommel model for subtropical gyres with the quasi-geostrophic balance between pressure gradient, Coriolis force, wind stress and friction driving the circulation. Parameters including water depth, natural dissipation rate and wind stress are calibrated in the model so that the model can reproduce reasonable flow properties including volume flux and energy flux. To represent flow dissipation due to turbines additional turbine drag coefficient is formulated and included in the model. Secondly, to determine the reasonableness of the total power

  20. Proteome-wide analysis of the amino terminal status of Escherichia coli proteins at the steady-state and upon deformylation inhibition.

    PubMed

    Bienvenut, Willy V; Giglione, Carmela; Meinnel, Thierry

    2015-07-01

    A proteome wide analysis was performed in Escherichia coli to identify the impact on protein N-termini of actinonin, an antibiotic specifically inhibiting peptide deformylase (PDF). A strategy and tool suite (SILProNaQ) was employed to provide large-scale quantitation of N-terminal modifications. In control conditions, more than 1000 unique N-termini were identified with 56% showing initiator methionine removal. Additional modifications corresponded to partial or complete Nα-acetylation (10%) and N-formyl retention (5%). Among the proteins undergoing these N-terminal modifications, 140 unique N-termini from translocated membrane proteins were highlighted. The very early time-course impact of actinonin was followed after addition of bacteriostatic concentrations of the drug. Under these conditions, 26% of all proteins did not undergo deformylation any longer after 10 min, a value reaching more than 60% of all characterized proteins after 40 min of treatment. The N-formylation ratio measured on individual proteins increased with the same trend. Upon early PDF inhibition, two major categories of proteins retained their N-formyl group: a large number of inner membrane proteins and many proteins involved in protein synthesis including factors assisting the nascent chains in early cotranslational events. All MS data have been deposited in the ProteomeXchange with identifiers PXD001979, PXD002012 and PXD001983 (http://proteomecentral.proteomexchange.org/dataset/PXD001979, http://proteomecentral.proteomexchange.org/dataset/PXD002012 and http://proteomecentral.proteomexchange.org/dataset/PXD001983). PMID:26017780

  1. The History of Liquid Ear Acupuncture and the Current Scientific State of the Art

    PubMed Central

    2016-01-01

    This short review article presents a current overview of existing publications and scientific results regarding liquid (ear) acupuncture. The injection of liquids into defined acupuncture points of the ear is not a method commonly used in the Western world. The term liquid acupuncture has different definitions, which makes understanding each definition and differentiating one from the other difficult. General terms like pharmacopuncture, homeosiniatry, and liquid acupuncture, which all describe the method of injecting different kinds of drugs into a defined body acupuncture point, are used. This article presents the history of liquid acupuncture, as well as the current scientific state of the art, from the point of view of two European researchers. Some articles are discussed and a few practical examples are presented. PMID:27386143

  2. The History of Liquid Ear Acupuncture and the Current Scientific State of the Art.

    PubMed

    Litscher, Daniela; Litscher, Gerhard

    2016-06-01

    This short review article presents a current overview of existing publications and scientific results regarding liquid (ear) acupuncture. The injection of liquids into defined acupuncture points of the ear is not a method commonly used in the Western world. The term liquid acupuncture has different definitions, which makes understanding each definition and differentiating one from the other difficult. General terms like pharmacopuncture, homeosiniatry, and liquid acupuncture, which all describe the method of injecting different kinds of drugs into a defined body acupuncture point, are used. This article presents the history of liquid acupuncture, as well as the current scientific state of the art, from the point of view of two European researchers. Some articles are discussed and a few practical examples are presented. PMID:27386143

  3. [Pathological gambling and computergame-addiction. Current state of research regarding two subtypes of behavioural addiction].

    PubMed

    Wölfling, K; Müller, K W

    2010-04-01

    Behavioral addictions, like pathological gambling and computer game addiction (or internet addiction), have become a growing concern in research and public interest. Currently similarities between behavioral addictions and substance dependency are controversially discussed in the scientific community. Unfortunately a mismatch exists between the large number of people seeking treatment and the small number of scientific studies on pathological gambling and computer game addiction. Prevalence of pathological gambling among the German population is estimated to be 0.2-0.5%. These estimations are comparable to prevalence rates reported for drug dependency. Latest research states that about 3% of German adolescents and young adults are believed to suffer from computer game addiction. Therefore, it is important to enhance investigations regarding the clinical and neuroscientific basis of computer game addiction. This review offers a summary of current results of research regarding pathological gambling and internet addiction. The phenomenological description of these two disorders is meant to allow a deeper understanding of behavioral addictions. PMID:20195558

  4. The modern brain tumor operating room: from standard essentials to current state-of-the-art.

    PubMed

    Barnett, Gene H; Nathoo, Narendra

    2004-01-01

    It is just over a century since successful brain tumor resection. Since then the diagnosis, imaging, and management of brain tumors have improved, in large part due to technological advances. Similarly, the operating room (OR) for brain tumor surgery has increased in complexity and specificity with multiple forms of equipment now considered necessary as technical adjuncts. It is evident that the theme of minimalism in combination with advanced image-guidance techniques and a cohort of sophisticated technologies (e.g., robotics and nanotechnology) will drive changes in the current OR environment for the foreseeable future. In this report we describe what may be regarded today as standard essentials in an operating room for the surgical management of brain tumors and what we believe to be the current 'state-of-the-art' brain tumor OR. Also, we speculate on the additional capabilities of the brain tumor OR of the near future. PMID:15527078

  5. Biomanufacturing of Therapeutic Cells: State of the Art, Current Challenges, and Future Perspectives.

    PubMed

    Roh, Kyung-Ho; Nerem, Robert M; Roy, Krishnendu

    2016-06-01

    Stem cells and other functionally defined therapeutic cells (e.g., T cells) are promising to bring hope of a permanent cure for diseases and disorders that currently cannot be cured by conventional drugs or biological molecules. This paradigm shift in modern medicine of using cells as novel therapeutics can be realized only if suitable manufacturing technologies for large-scale, cost-effective, reproducible production of high-quality cells can be developed. Here we review the state of the art in therapeutic cell manufacturing, including cell purification and isolation, activation and differentiation, genetic modification, expansion, packaging, and preservation. We identify current challenges and discuss opportunities to overcome them such that cell therapies become highly effective, safe, and predictively reproducible while at the same time becoming affordable and widely available. PMID:27276552

  6. Current-State Constrained Filter Bank for Wald Testing of Spacecraft Conjunctions

    NASA Technical Reports Server (NTRS)

    Carpenter, J. Russell; Markley, F. Landis

    2012-01-01

    We propose a filter bank consisting of an ordinary current-state extended Kalman filter, and two similar but constrained filters: one is constrained by a null hypothesis that the miss distance between two conjuncting spacecraft is inside their combined hard body radius at the predicted time of closest approach, and one is constrained by an alternative complementary hypothesis. The unconstrained filter is the basis of an initial screening for close approaches of interest. Once the initial screening detects a possibly risky conjunction, the unconstrained filter also governs measurement editing for all three filters, and predicts the time of closest approach. The constrained filters operate only when conjunctions of interest occur. The computed likelihoods of the innovations of the two constrained filters form a ratio for a Wald sequential probability ratio test. The Wald test guides risk mitigation maneuver decisions based on explicit false alarm and missed detection criteria. Since only current-state Kalman filtering is required to compute the innovations for the likelihood ratio, the present approach does not require the mapping of probability density forward to the time of closest approach. Instead, the hard-body constraint manifold is mapped to the filter update time by applying a sigma-point transformation to a projection function. Although many projectors are available, we choose one based on Lambert-style differential correction of the current-state velocity. We have tested our method using a scenario based on the Magnetospheric Multi-Scale mission, scheduled for launch in late 2014. This mission involves formation flight in highly elliptical orbits of four spinning spacecraft equipped with antennas extending 120 meters tip-to-tip. Eccentricities range from 0.82 to 0.91, and close approaches generally occur in the vicinity of perigee, where rapid changes in geometry may occur. Testing the method using two 12,000-case Monte Carlo simulations, we found the

  7. State-of-Art Empirical Modeling of Ring Current Plasma Pressure

    NASA Astrophysics Data System (ADS)

    Yue, C.; Ma, Q.; Wang, C. P.; Bortnik, J.; Thorne, R. M.

    2015-12-01

    The plasma pressure in the inner magnetosphere plays a key role in plasma dynamics by changing magnetic field configurations and generating the ring current. In this study, we present our preliminary results of empirically constructing 2D equatorial ring current pressure and pressure anisotropy spatial distributions controlled by Dst based on measurements from two particle instruments (HOPE and RBSPICE) onboard Van Allen Probes. We first obtain the equatorial plasma perpendicular and parallel pressures for different species including H+, He+, O+ and e- from 20 eV to ~1 MeV, and investigate their relative contributions to the total plasma pressure and pressure anisotropy. We then establish empirical equatorial pressure models within ~ 6 RE using a state-of-art machine learning technique, Support Vector Regression Machine (SVRM). The pressure models predict equatorial perpendicular and parallel plasma thermal pressures (for each species and for total pressures) and pressure anisotropy at any given r, MLT, Bz/Br (equivalent Z distance), and Dst within applicable ranges. We are currently validating our model predictions and investigating how the ring current pressure distributions and the associated pressure gradients vary with Dst index.

  8. Mid to late Holocene Leeuwin Current variability offshore southern Australia linked to ENSO state changes

    NASA Astrophysics Data System (ADS)

    Perner, Kerstin; Moros, Matthias; De Deckker, Patrick; Blanz, Thomas; Siegel, Herbert; Wacker, Lukas; Schneider, Ralph; Jansen, Eystein

    2015-04-01

    The El Niño-Southern Oscillation (ENSO), a key aspect of the Earth's climate, drives regional to global oceanic and climate changes on various time-scales. Differences in the temporal coverage of Holocene records for the more general state in El Niño frequency, however, restrict a comprehensive overview. Oceanic variability offshore southern Australia is linked to the Leeuwin Current (LC), an eastern boundary current, transporting tropical waters from the Indo Pacific Warm Pool region towards higher latitudes. Instrumental data, spanning the last few decades, document that ENSO modulates LC variability. Here we present new, well-dated time series from two marine sediment cores (MD03-2611 and SS0206-GC 15)of past LC variability, based on alkenone-derived sea-surface temperatures (SST) and planktonic foraminifera offshore southern Australia, an area affected by recent El Niño and La Niña events. Our reconstructions of ENSO-state changes cover the last 7,400 years. With transition into the mid Holocene [dates], we find clear evidence that oceanic conditions prevailed under the dominant influence of a persistent La Niña mode. A strong LC produces a stratified water column and establishes a permanent thermocline as seen in the high abundance of the 'tropical fauna' (Globoturborotalita rubescens, Globoturborotalita tenella and Globigerinella sacculifer (including G. trilobus)) and maximum SST offshore southern Australia. During this La Niña-state dominated period, we record at c. 5000 years BP the first short period of a strong El Niño-like-state, by a pronounced drop in abundance of the subtropical species Globigerinoides ruber and a reduced SST gradient between the two core sites. The Late Holocene (from 3,500 years BP onwards) period is characterized by centennial to millennial scale variability in the LC strength, which is accompanied by an overall decrease of SSTs offshore southern Australia. We link this LC variability to Late Holocene centennial

  9. Steady State Properties of Lock-On Current Filaments in GaAs

    NASA Astrophysics Data System (ADS)

    Kambour, K.; Kang, Samsoo; Myles, Charles W.; Hjalmarson, Harold P.

    1999-10-01

    Collective impact ionization has been used by Hjalmarson et al.(H. Hjalmarson, F. Zutavern, G. Loubriel, A. Baca, and D. Wake, Sandia Report SAND93-3972(1996).) to explain the lock-on effect, observed in optically activated, semi-insulating GaAs switches. We have used this theory to study some of the steady state properties of the lock-on current filaments which accompany this effect. In steady state, the energy gained from the electric field is exactly compensated for by the the energy lost due to the phonon cooling of the hot carriers. In the simplest approximation, the carrier distribution approaches a quasi-equilibrium Maxwell-Boltzmann distribution. In this presentation we report preliminary results on the validity of this quasi-equilibrium approximation. We find that this approximation leads to a filament carrier density which is much lower than the high density needed to achieve a quasi-equilibrium distribution. Further work is in progress.

  10. Current Guidelines, Common Clinical Pitfalls, and Future Directions for Laboratory Diagnosis of Lyme Disease, United States.

    PubMed

    Moore, Andrew; Nelson, Christina; Molins, Claudia; Mead, Paul; Schriefer, Martin

    2016-07-01

    In the United States, Lyme disease is caused by Borrelia burgdorferi and transmitted to humans by blacklegged ticks. Patients with an erythema migrans lesion and epidemiologic risk can receive a diagnosis without laboratory testing. For all other patients, laboratory testing is necessary to confirm the diagnosis, but proper interpretation depends on symptoms and timing of illness. The recommended laboratory test in the United States is 2-tiered serologic analysis consisting of an enzyme-linked immunoassay or immunofluorescence assay, followed by reflexive immunoblotting. Sensitivity of 2-tiered testing is low (30%-40%) during early infection while the antibody response is developing (window period). For disseminated Lyme disease, sensitivity is 70%-100%. Specificity is high (>95%) during all stages of disease. Use of other diagnostic tests for Lyme disease is limited. We review the rationale behind current US testing guidelines, appropriate use and interpretation of tests, and recent developments in Lyme disease diagnostics. PMID:27314832

  11. Current Guidelines, Common Clinical Pitfalls, and Future Directions for Laboratory Diagnosis of Lyme Disease, United States

    PubMed Central

    Moore, Andrew; Nelson, Christina; Molins, Claudia; Mead, Paul

    2016-01-01

    In the United States, Lyme disease is caused by Borrelia burgdorferi and transmitted to humans by blacklegged ticks. Patients with an erythema migrans lesion and epidemiologic risk can receive a diagnosis without laboratory testing. For all other patients, laboratory testing is necessary to confirm the diagnosis, but proper interpretation depends on symptoms and timing of illness. The recommended laboratory test in the United States is 2-tiered serologic analysis consisting of an enzyme-linked immunoassay or immunofluorescence assay, followed by reflexive immunoblotting. Sensitivity of 2-tiered testing is low (30%–40%) during early infection while the antibody response is developing (window period). For disseminated Lyme disease, sensitivity is 70%–100%. Specificity is high (>95%) during all stages of disease. Use of other diagnostic tests for Lyme disease is limited. We review the rationale behind current US testing guidelines, appropriate use and interpretation of tests, and recent developments in Lyme disease diagnostics. PMID:27314832

  12. Learning Styles of Pilots Currently Qualified in United States Air Force Aircraft

    NASA Technical Reports Server (NTRS)

    Kanske, Craig A.

    2001-01-01

    Kolb's Learning Style Inventory was used to identify the predominant learning styles of pilots currently qualified in United States Air Force aircraft. The results indicate that these pilots show a significant preference for facts and things over people and feelings. By understanding the preferred learning styles of the target population, course material can be developed that take advantage of the strengths of these learning styles. This information can be especially useful in the future design of cockpit resource management training. The training program can be developed to demonstrate both that there are different learning styles and that it is possible to take advantage of the relative strengths of each of these learning styles.

  13. Globalization of Gerontology Education: Current Practices and Perceptions for Graduate Gerontology Education in the United States

    PubMed Central

    MWANGI, SAMUEL M.; YAMASHITA, TAKASHI; EWEN, HEIDI H.; MANNING, LYDIA K.; KUNKEL, SUZANNE R.

    2013-01-01

    The purpose of this study is to document current practices and understandings about globalization of gerontology education in the United States. Better understanding of aging requires international perspectives in global communities. However, little is known about how globalization of gerontology education is practiced in U.S. graduate-level degree programs. The authors conducted qualitative interviews with representatives of the Association for Gerontology in Higher Education, the major national organization supporting higher education in gerontology, graduate program directors, and students. Although all respondents expressed their interest in globalizing gerontology education, actual practices are diverse. The authors discuss suggested conceptualization and strategies for globalizing gerontology education. PMID:22490075

  14. Modern energy density functional and the current status of the equation of state of nuclear matter

    SciTech Connect

    Shlomo, S.

    2012-11-20

    We first describe a method, based on the simulated annealing approach, for determining a modern energy density functional within the Skyrme Hartree-Fock (HF) theory by carrying out a fit to extensive set of experimental data with additional constraints on the Skyrme parameters. Next, we review the HF-based random phase approximation (RPA) approach for calculating properties of giant resonances. We then present results of calculations for the centroid energies of giant resonances within the HF-based RPA and discuss the current status of the equation of state of nuclear matter.

  15. Microstates in resting-state EEG: current status and future directions.

    PubMed

    Khanna, Arjun; Pascual-Leone, Alvaro; Michel, Christoph M; Farzan, Faranak

    2015-02-01

    Electroencephalography (EEG) is a powerful method of studying the electrophysiology of the brain with high temporal resolution. Several analytical approaches to extract information from the EEG signal have been proposed. One method, termed microstate analysis, considers the multichannel EEG recording as a series of quasi-stable "microstates" that are each characterized by a unique topography of electric potentials over the entire channel array. Because this technique simultaneously considers signals recorded from all areas of the cortex, it is capable of assessing the function of large-scale brain networks whose disruption is associated with several neuropsychiatric disorders. In this review, we first introduce the method of EEG microstate analysis. We then review studies that have discovered significant changes in the resting-state microstate series in a variety of neuropsychiatric disorders and behavioral states. We discuss the potential utility of this method in detecting neurophysiological impairments in disease and monitoring neurophysiological changes in response to an intervention. Finally, we discuss how the resting-state microstate series may reflect rapid switching among neural networks while the brain is at rest, which could represent activity of resting-state networks described by other neuroimaging modalities. We conclude by commenting on the current and future status of microstate analysis, and suggest that EEG microstates represent a promising neurophysiological tool for understanding and assessing brain network dynamics on a millisecond timescale in health and disease. PMID:25526823

  16. Microstates in Resting-State EEG: Current Status and Future Directions

    PubMed Central

    Khanna, Arjun; Pascual-Leone, Alvaro; Michel, Christoph M.; Farzan, Faranak

    2015-01-01

    Electroencephalography (EEG) is a powerful method of studying the electrophysiology of the brain with high temporal resolution. Several analytical approaches to extract information from the EEG signal have been proposed. One method, termed microstate analysis, considers the multichannel EEG recording as a series of quasi-stable “microstates” that are each characterized by a unique topography of electric potentials over the entire channel array. Because this technique simultaneously considers signals recorded from all areas of the cortex, it is capable of assessing the function of large-scale brain networks whose disruption is associated with several neuropsychiatric disorders. In this review, we first introduce the method of EEG microstate analysis. We then review studies that have discovered significant changes in the resting-state microstate series in a variety of neuropsychiatric disorders and behavioral states. We discuss the potential utility of this method in detecting neurophysiological impairments in disease and monitoring neurophysiological changes in response to an intervention. Finally, we discuss how the resting-state microstate series may reflect rapid switching among neural networks while the brain is at rest, which could represent activity of resting-state networks described by other neuroimaging modalities. We conclude by commenting on the current and future status of microstate analysis, and suggest that EEG microstates represent a promising neurophysiological tool for understanding and assessing brain network dynamics on a millisecond timescale in health and disease. PMID:25526823

  17. Proteomic Assessment of Poultry Spermatozoa

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Fully characterizing the protein composition of spermatozoa is the first step in utilizing proteomics to delineate the function of sperm proteins. To date, sperm proteome maps have been partially developed for the human, mouse, rat, bull and several invertebrates. Here we report the first proteomic...

  18. Mining Proteomes Using Bioorthogonal Probes.

    PubMed

    Wu, Haoxing; Devaraj, Neal K

    2016-07-21

    The definition of proteomes in cells and animals at particular stages facilitates an understanding of protein function. In this issue of Cell Chemical Biology, Elliott et al. (2016) report an elegant approach of bioorthogonal labeling and enrichment of proteomes from stochastic orthogonal recoding of translation. With this method, low abundance proteomes can be identified in a multicellular system. PMID:27447043

  19. The plasma environment, charge state, and currents of Saturn's C and D rings

    SciTech Connect

    Wilson, G.R. )

    1991-06-01

    The plasma environment of the Saturnian C and D rings is investigated by modeling the flow of ionospheric plasma from the mid- to low-latitude ionosphere to the vicinity of the rings. The model used is time-dependent and kinetic and incorporates the gravitational, centripetal, magnetic mirror and ambipolar electric forces. It was found that the plasma density near the C and D rings, at a given radial location, will experience a one to two order of magnitude diurnal variation. With a knowledge of the plasma density and temperature near these rings their charge state is investigated by use of a dust cloud charging model. The associated azimuthal currents are also found. Results show that the surface charge density of the C and D rings can show significant radial and azimuthal variations, due mainly to variations in the plasma density. In addition to its plasma density and temperature dependence the surface charge density will also depend on structural features of the rings such as the ring thickness and the nature of the particle size distribution. Its magnitude may vary over seven decades. The associated azimuthal currents carried by these rings will also show large diurnal variations resulting in field-aligned currents which close in the ionosphere as shown by Ip and Mendis (1983). However, the resulting ionospheric electric fields will probably not produce a significant amount of plasma convection in the topside ionosphere and inner plasmasphere as proposed by these authors, due in part to the level of the currents as well as the height-integrated Pedersen conductivities at the local times where the currents close.

  20. Mass Casualty Decontamination in the United States: An Online Survey of Current Practice.

    PubMed

    Power, Sarah; Symons, Charles; Carter, Holly; Jones, Emma; Amlôt, Richard; Larner, Joanne; Matar, Hazem; Chilcott, Robert P

    2016-01-01

    Mass casualty decontamination is a public health intervention that would be employed by emergency responders following a chemical, biological, or radiological incident. The decontamination of large numbers of casualties is currently most often performed with water to remove contaminants from the skin surface. An online survey was conducted to explore US fire departments' decontamination practices and their preparedness for responding to incidents involving mass casualty decontamination. Survey respondents were asked to provide details of various aspects of their decontamination procedures, including expected response times to reach casualties, disrobing procedures, approaches to decontamination, characteristics of the decontamination showering process, provision for special populations, and any actions taken following decontamination. The aim of the survey was to identify any differences in the way in which decontamination guidance is implemented across US states. Results revealed that, in line with current guidance, many US fire departments routinely use the "ladder-pipe system" for conducting rapid, gross decontamination of casualties. The survey revealed significant variability in ladder-pipe construction, such as the position and number of fire hoses used. There was also variability in decontamination characteristics, such as water temperature and water pressure, detergent use, and shower duration. The results presented here provide important insights into the ways in which implementation of decontamination guidance can vary between US states. These inconsistencies are thought to reflect established perceived best practices and local adaptation of response plans to address practical and logistical constraints. These outcomes highlight the need for evidence-based national guidelines for conducting mass casualty decontamination. PMID:27442794

  1. Factors that affect action possibility judgements: recent experience with the action and the current body state.

    PubMed

    Chandrasekharan, Sanjay; Binsted, Gordon; Ayres, Fabio; Higgins, Laura; Welsh, Timothy N

    2012-01-01

    It has been suggested that action possibility judgements are formed through a covert simulation of the to-be-executed action. We sought to determine whether the motor system (via a common coding mechanism) influences this simulation, by investigating whether action possibility judgements are influenced by experience with the movement task (Experiments 1 and 2) and current body states (Experiment 3). The judgement task in each experiment involved judging whether it was possible for a person's hand to accurately move between two targets at presented speeds. In Experiment 1, participants completed the action judgements before and after executing the movement they were required to judge. Results were that judged movement times after execution were closer to the actual execution time than those prior to execution. The results of Experiment 2 suggest that the effects of execution on judgements were not due to motor activation or perceptual task experience-alternative explanations of the execution-mediated judgement effects. Experiment 3 examined how judged movement times were influenced by participants wearing weights. Results revealed that wearing weights increased judged movement times. These results suggest that the simulation underlying the judgement process is connected to the motor system, and that simulations are dynamically generated, taking into account recent experience and current body state. PMID:22348464

  2. Interconnections between magnetic state and transport currents in antiferromagnetic Sr2IrO4

    NASA Astrophysics Data System (ADS)

    Tsoi, Maxim

    Interconnections between magnetic state and transport currents in ferromagnetic (F) heterostructures are the basis for spintronic applications, e.g. tunneling magnetoresistance and spin-transfer torque phenomena provide a means to read and write information in magnetic memory devices like STTRAM. Similar interconnections were proposed to occur in systems where F-components are replaced with antiferromagnets (AFM). We demonstrated experimentally the existence of such interconnections in antiferromagnetic Mott insulator Sr2IrO4: first, we found a very large anisotropic magnetoresistance (AMR) which can be used to monitor (read) the magnetic state of AFM; second, we demonstrated the feasibility of reversible resistive switching driven by high-density currents/high electric fields which can be used for writing in AFM memory applications. These results support the feasibility of AFM spintronics where antiferromagnets are used in place of ferromagnets. This work was supported in part by C-SPIN, one of six centers of STARnet, a Semiconductor Research Corporation program, sponsored by MARCO and DARPA, and by NSF grants DMR-1207577, DMR-1265162 and DMR-1122603.

  3. Transient analysis and control of bias magnetic state in the transformer of on-line pulse-width-modulation switching full bridge direct current-direct current converter

    NASA Astrophysics Data System (ADS)

    Chen, Jiaxin; Guo, Youguang; Zhu, Jianguo; Wei Lin, Zhi

    2012-04-01

    This paper presents a finite element analysis (FEA) based method for analyzing and controlling the bias magnetic state of the transformer of a pulse-width-modulation (PWM) switching full bridge dc-dc converter. A field-circuit indirect coupling method for predicting the transient bias magnetic state is introduced first. To increase flexibility of the proposed method, a novel transformer model which can address not only its basic input-output characteristic, but also the nonlinear magnetizing inductance, is proposed. Both the asymmetric characteristic and the variable laws of the current flowing through the two secondary windings during the period of PWM switching-off state are highlighted. Finally, the peak magnetizing current controlled method based on the on-line magnetizing current computation is introduced. Analysis results show that this method can address the magnetic saturation at winding ends, and hence many previous difficulties, such as the start-up process and asymmetry of power electronics, can be easily controlled.

  4. A Quantitative Proteomics Analysis of Subcellular Proteome Localization and Changes Induced by DNA Damage*

    PubMed Central

    Boisvert, François-Michel; Lam, Yun Wah; Lamont, Douglas; Lamond, Angus I.

    2010-01-01

    A major challenge in cell biology is to identify the subcellular distribution of proteins within cells and to characterize how protein localization changes under different cell growth conditions and in response to stress and other external signals. Protein localization is usually determined either by microscopy or by using cell fractionation combined with protein blotting techniques. Both these approaches are intrinsically low throughput and limited to the analysis of known components. Here we use mass spectrometry-based proteomics to provide an unbiased, quantitative, and high throughput approach for measuring the subcellular distribution of the proteome, termed “spatial proteomics.” The spatial proteomics method analyzes a whole cell extract created by recombining differentially labeled subcellular fractions derived from cells in which proteins have been mass-labeled with heavy isotopes. This was used here to measure the relative distribution between cytoplasm, nucleus, and nucleolus of over 2,000 proteins in HCT116 cells. The data show that, at steady state, the proteome is predominantly partitioned into specific subcellular locations with only a minor subset of proteins equally distributed between two or more compartments. Spatial proteomics also facilitates a proteome-wide comparison of changes in protein localization in response to a wide range of physiological and experimental perturbations, shown here by characterizing dynamic changes in protein localization elicited during the cellular response to DNA damage following treatment of HCT116 cells with etoposide. DNA damage was found to cause dissociation of the proteasome from inhibitory proteins and assembly chaperones in the cytoplasm and relocation to associate with proteasome activators in the nucleus. PMID:20026476

  5. Environmental Proteomics: a Paradigm Shift in Characterizing Microbial Activities at the Molecular Level

    SciTech Connect

    Hettich, Robert {Bob} L

    2009-01-01

    The increase in sequencing capacity led to a new wave of metagenomic projects, enabling and setting the prerequisite for the application of environmental proteomics technologies. This review describes the current status of environmental proteomics. It describes sample preparation as well as the two major technologies applied within this field: two-dimensional electrophoresis-based environmental proteomics and liquid chromatography-mass spectrometry-based environmental proteomics. It also highlights current publications and describes major scientific findings. The review closes with a discussion of critical improvements in the area of integrating experimental mass spectrometry technologies with bioinformatics as well as improved sample handling.

  6. Progress Toward Steady State Tokamak Operation Exploiting the high bootstrap current fraction regime

    NASA Astrophysics Data System (ADS)

    Ren, Q.

    2015-11-01

    Recent DIII-D experiments have advanced the normalized fusion performance of the high bootstrap current fraction tokamak regime toward reactor-relevant steady state operation. The experiments, conducted by a joint team of researchers from the DIII-D and EAST tokamaks, developed a fully noninductive scenario that could be extended on EAST to a demonstration of long pulse steady-state tokamak operation. Fully noninductive plasmas with extremely high values of the poloidal beta, βp >= 4 , have been sustained at βT >= 2 % for long durations with excellent energy confinement quality (H98y,2 >= 1 . 5) and internal transport barriers (ITBs) generated at large minor radius (>= 0 . 6) in all channels (Te, Ti, ne, VTf). Large bootstrap fraction (fBS ~ 80 %) has been obtained with high βp. ITBs have been shown to be compatible with steady state operation. Because of the unusually large ITB radius, normalized pressure is not limited to low βN values by internal ITB-driven modes. βN up to ~4.3 has been obtained by optimizing the plasma-wall distance. The scenario is robust against several variations, including replacing some on-axis with off-axis neutral beam injection (NBI), adding electron cyclotron (EC) heating, and reducing the NBI torque by a factor of 2. This latter observation is particularly promising for extension of the scenario to EAST, where maximum power is obtained with balanced NBI injection, and to a reactor, expected to have low rotation. However, modeling of this regime has provided new challenges to state-of-the-art modeling capabilities: quasilinear models can dramatically underpredict the electron transport, and the Sauter bootstrap current can be insufficient. The analysis shows first-principle NEO is in good agreement with experiments for the bootstrap current calculation and ETG modes with a larger saturated amplitude or EM modes may provide the missing electron transport. Work supported in part by the US DOE under DE-FC02-04ER54698, DE-AC52-07NA

  7. [Cardiovascular proteomics: challenges and opportunities for cardiologists of the future].

    PubMed

    Banfi, Cristina; Brioschi, Maura; Tremoli, Elena

    2013-01-01

    Proteomics is the study of the "proteome", that is the entire protein complement of a genome. However, it is well recognized that the proteome is far more complex than previously suggested by the "one-gene, one-protein" central dogma of biology. The proteome encompasses all proteins of a cell or organism at a given time, including not only those translated directly from genetic information but also the array of modified proteins arising from alternative splicing of transcripts and post-translational processing, resulting in modifications that have the potential to alter protein structure or biological function. As proteins are involved in virtually every cellular function, control every regulatory mechanism, and are modified in disease states, the proteome dictates the phenotype of the cell and, consequently, the tissue or organ that the cells comprise. This results in a dynamic, ongoing process of protein expression and modifications. The proteome thus consists of information from protein expression, post-translational modifications, processing and turnover, localization and time. Proteomics is aimed at identifying and characterizing these protein changes and, if applied to the field of cardiovascular sciences, it has the potential to reveal those proteins that are associated with pathogenesis and could be potentially used as predictive or prognostic markers. Cardioproteomic is still in its infancy and relatively few cardiovascular diseases have been investigated. However, it has enormously increased our knowledge of the complexity of the myocardium in terms of protein composition at cellular and organelle levels. The cardiac proteome is further complicated by protein post-translational modifications, which may regulate organelle function in physiological and pathological conditions. Therefore, the incorporation of proteomics into cardiovascular research will provide a means of exploring the mechanisms of disease onset and progression. This will in turn ultimately

  8. High-Throughput Proteomics

    NASA Astrophysics Data System (ADS)

    Zhang, Zhaorui; Wu, Si; Stenoien, David L.; Paša-Tolić, Ljiljana

    2014-06-01

    Mass spectrometry (MS)-based high-throughput proteomics is the core technique for large-scale protein characterization. Due to the extreme complexity of proteomes, sophisticated separation techniques and advanced MS instrumentation have been developed to extend coverage and enhance dynamic range and sensitivity. In this review, we discuss the separation and prefractionation techniques applied for large-scale analysis in both bottom-up (i.e., peptide-level) and top-down (i.e., protein-level) proteomics. Different approaches for quantifying peptides or intact proteins, including label-free and stable-isotope-labeling strategies, are also discussed. In addition, we present a brief overview of different types of mass analyzers and fragmentation techniques as well as selected emerging techniques.

  9. Establishing Substantial Equivalence: Proteomics

    NASA Astrophysics Data System (ADS)

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

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

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

    PubMed

    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/). PMID:25913743

  11. Integrated modelling of steady-state scenarios and heating and current drive mixes for ITER

    SciTech Connect

    Murakami, Masanori; Park, Jin Myung

    2011-01-01

    Recent progress on ITER steady-state (SS) scenario modelling by the ITPA-IOS group is reviewed. Code-to-code benchmarks as the IOS group's common activities for the two SS scenarios (weak shear scenario and internal transport barrier scenario) are discussed in terms of transport, kinetic profiles, and heating and current drive (CD) sources using various transport codes. Weak magnetic shear scenarios integrate the plasma core and edge by combining a theory-based transport model (GLF23) with scaled experimental boundary profiles. The edge profiles (at normalized radius rho = 0.8-1.0) are adopted from an edge-localized mode-averaged analysis of a DIII-D ITER demonstration discharge. A fully noninductive SS scenario is achieved with fusion gain Q = 4.3, noninductive fraction f(NI) = 100%, bootstrap current fraction f(BS) = 63% and normalized beta beta(N) = 2.7 at plasma current I(p) = 8MA and toroidal field B(T) = 5.3 T using ITER day-1 heating and CD capability. Substantial uncertainties come from outside the radius of setting the boundary conditions (rho = 0.8). The present simulation assumed that beta(N)(rho) at the top of the pedestal (rho = 0.91) is about 25% above the peeling-ballooning threshold. ITER will have a challenge to achieve the boundary, considering different operating conditions (T(e)/T(i) approximate to 1 and density peaking). Overall, the experimentally scaled edge is an optimistic side of the prediction. A number of SS scenarios with different heating and CD mixes in a wide range of conditions were explored by exploiting the weak-shear steady-state solution procedure with the GLF23 transport model and the scaled experimental edge. The results are also presented in the operation space for DT neutron power versus stationary burn pulse duration with assumed poloidal flux availability at the beginning of stationary burn, indicating that the long pulse operation goal (3000s) at I(p) = 9 MA is possible. Source calculations in these simulations have been

  12. Change in Mean Frequency of Resting-State Electroencephalography after Transcranial Direct Current Stimulation.

    PubMed

    Boonstra, Tjeerd W; Nikolin, Stevan; Meisener, Ann-Christin; Martin, Donel M; Loo, Colleen K

    2016-01-01

    Transcranial direct current stimulation (tDCS) is proposed as a tool to investigate cognitive functioning in healthy people and as a treatment for various neuropathological disorders. However, the underlying cortical mechanisms remain poorly understood. We aim to investigate whether resting-state electroencephalography (EEG) can be used to monitor the effects of tDCS on cortical activity. To this end we tested whether the spectral content of ongoing EEG activity is significantly different after a single session of active tDCS compared to sham stimulation. Twenty participants were tested in a sham-controlled, randomized, crossover design. Resting-state EEG was acquired before, during and after active tDCS to the left dorsolateral prefrontal cortex (15 min of 2 mA tDCS) and sham stimulation. Electrodes with a diameter of 3.14 cm(2) were used for EEG and tDCS. Partial least squares (PLS) analysis was used to examine differences in power spectral density (PSD) and the EEG mean frequency to quantify the slowing of EEG activity after stimulation. PLS revealed a significant increase in spectral power at frequencies below 15 Hz and a decrease at frequencies above 15 Hz after active tDCS (P = 0.001). The EEG mean frequency was significantly reduced after both active tDCS (P < 0.0005) and sham tDCS (P = 0.001), though the decrease in mean frequency was smaller after sham tDCS than after active tDCS (P = 0.073). Anodal tDCS of the left DLPFC using a high current density bi-frontal electrode montage resulted in general slowing of resting-state EEG. The similar findings observed following sham stimulation question whether the standard sham protocol is an appropriate control condition for tDCS. PMID:27375462

  13. Change in Mean Frequency of Resting-State Electroencephalography after Transcranial Direct Current Stimulation

    PubMed Central

    Boonstra, Tjeerd W.; Nikolin, Stevan; Meisener, Ann-Christin; Martin, Donel M.; Loo, Colleen K.

    2016-01-01

    Transcranial direct current stimulation (tDCS) is proposed as a tool to investigate cognitive functioning in healthy people and as a treatment for various neuropathological disorders. However, the underlying cortical mechanisms remain poorly understood. We aim to investigate whether resting-state electroencephalography (EEG) can be used to monitor the effects of tDCS on cortical activity. To this end we tested whether the spectral content of ongoing EEG activity is significantly different after a single session of active tDCS compared to sham stimulation. Twenty participants were tested in a sham-controlled, randomized, crossover design. Resting-state EEG was acquired before, during and after active tDCS to the left dorsolateral prefrontal cortex (15 min of 2 mA tDCS) and sham stimulation. Electrodes with a diameter of 3.14 cm2 were used for EEG and tDCS. Partial least squares (PLS) analysis was used to examine differences in power spectral density (PSD) and the EEG mean frequency to quantify the slowing of EEG activity after stimulation. PLS revealed a significant increase in spectral power at frequencies below 15 Hz and a decrease at frequencies above 15 Hz after active tDCS (P = 0.001). The EEG mean frequency was significantly reduced after both active tDCS (P < 0.0005) and sham tDCS (P = 0.001), though the decrease in mean frequency was smaller after sham tDCS than after active tDCS (P = 0.073). Anodal tDCS of the left DLPFC using a high current density bi-frontal electrode montage resulted in general slowing of resting-state EEG. The similar findings observed following sham stimulation question whether the standard sham protocol is an appropriate control condition for tDCS. PMID:27375462

  14. Targeted Proteomics Approaches To Monitor Microbial Activity In Basalt Aquifer

    NASA Astrophysics Data System (ADS)

    Paszczynski, A. J.; Paidisetti, R.

    2007-12-01

    Microorganisms play a major role in biogeochemical cycles of the Earth. Information regarding microbial community composition can be very useful for environmental monitoring since the short generation times of microorganisms allows them to respond rapidly to changing environmental conditions. Microbial mediated attenuation of toxic chemicals offers great potential for the restoration of contaminated environments in an ecologically acceptable manner. Current knowledge regarding the structure and functional activities of microbial communities is limited, but more information is being acquired every day through many genomic- and proteomic- based methods. As of today, only a small fraction of the Earth's microorganisms has been cultured, and so most of the information regarding the biodegradation and therapeutic potentials of these uncultured microorganisms remains unknown. Sequence analysis of DNA and/or RNA has been used for identifying specific microorganisms, to study the community composition, and to monitor gene expression providing limited information about metabolic state of given microbial system. Proteomic studies can reveal information regarding the real-time metabolic state of the microbial communities thereby aiding in understanding their interaction with the environment. In research described here the involvement of microbial communities in the degradation of anthropogenic contaminants such as trichloroethylene (TCE) was studied using mass spectrometry-based proteomics. The co- metabolic degradation of TCE in the groundwater of the Snake River Plain Aquifer at the Test Area North (TAN) site of Idaho National Laboratory (INL) was monitored by the characterization of peptide sequences of enzymes such as methane monooxygenases (MMOs). MMOs, expressed by methanotrophic bacteria are involved in the oxidation of methane and non-specific co-metabolic oxidation of TCE. We developed a time- course cell lysis method to release proteins from complex microbial

  15. Eyes wide shut: Transcranial alternating current stimulation drives alpha rhythm in a state dependent manner.

    PubMed

    Ruhnau, Philipp; Neuling, Toralf; Fuscá, Marco; Herrmann, Christoph S; Demarchi, Gianpaolo; Weisz, Nathan

    2016-01-01

    Transcranial alternating current stimulation (tACS) is used to modulate brain oscillations to measure changes in cognitive function. It is only since recently that brain activity in human subjects during tACS can be investigated. The present study aims to investigate the phase relationship between the external tACS signal and concurrent brain activity. Subjects were stimulated with tACS at individual alpha frequency during eyes open and eyes closed resting states. Electrodes were placed at Cz and Oz, which should affect parieto-occipital areas most strongly. Source space magnetoencephalography (MEG) data were used to estimate phase coherence between tACS and brain activity. Phase coherence was significantly increased in areas in the occipital pole in eyes open resting state only. The lag between tACS and brain responses showed considerable inter-individual variability. In conclusion, tACS at individual alpha frequency entrains brain activity in visual cortices. Interestingly, this effect is state dependent and is clearly observed with eyes open but only to a lesser extent with eyes closed. PMID:27252047

  16. Critical Current, Vortices and Fermionic Bound States in the BEC to BCS Crossover

    NASA Astrophysics Data System (ADS)

    Sensarma, Rajdeep; Randeria, Mohit; Lun Ho, Tin

    2006-03-01

    We have analyzed a single vortex at T=0 in a 3D superfluid atomic Fermi gas across a Feshbach resonance[1] using a fully self-consistent Bogoliubov-deGennes approach. From the current flow around a vortex we conclude that unitarity (as= ∞) is the most robust superfluid state in the entire BCS-BEC crossover, with the highest critical velocity vc of about 0.1vF. On either side of unitarity, vc decreases. It is determined by pair breaking on the BCS side and by collective excitations in the BEC regime. In the BCS limit, the order parameter near the vortex core shows a variation on both the scale of kF-1 and of the coherence length ξ, while away from the BCS limit only a variation on the scale of ξ is seen. The density in the core rises quadratically with radial distance and is progressively depleted as one moves from BCS to BEC. The number of fermionic bound states in the core decreases as we move from the BCS to BEC regime. Remarkably, a bound state branch persists even on the BEC side reflecting the composite nature of bosonic molecules.[1] R. Sensarma, M. Randeria and T.L. Ho, cond-mat/0510761

  17. Eyes wide shut: Transcranial alternating current stimulation drives alpha rhythm in a state dependent manner

    PubMed Central

    Ruhnau, Philipp; Neuling, Toralf; Fuscá, Marco; Herrmann, Christoph S.; Demarchi, Gianpaolo; Weisz, Nathan

    2016-01-01

    Transcranial alternating current stimulation (tACS) is used to modulate brain oscillations to measure changes in cognitive function. It is only since recently that brain activity in human subjects during tACS can be investigated. The present study aims to investigate the phase relationship between the external tACS signal and concurrent brain activity. Subjects were stimulated with tACS at individual alpha frequency during eyes open and eyes closed resting states. Electrodes were placed at Cz and Oz, which should affect parieto-occipital areas most strongly. Source space magnetoencephalography (MEG) data were used to estimate phase coherence between tACS and brain activity. Phase coherence was significantly increased in areas in the occipital pole in eyes open resting state only. The lag between tACS and brain responses showed considerable inter-individual variability. In conclusion, tACS at individual alpha frequency entrains brain activity in visual cortices. Interestingly, this effect is state dependent and is clearly observed with eyes open but only to a lesser extent with eyes closed. PMID:27252047

  18. Prevention of Meningococcal Infection in the United States: Current Recommendations and Future Considerations.

    PubMed

    Baker, Carol J

    2016-08-01

    Neisseria meningitidis is a common cause of bacterial meningitis and septicemia that can lead to permanent sequelae or death. N meningitidis is classified into serogroups based on the composition of the capsular polysaccharide, with serogroups A, B, C, W, X, and Y recognized as the major disease-causing organisms. The unpredictability of infection coupled with the poor prognosis for some patients suggests immunization as an effective preventive strategy. Importantly, four of the six disease-causing serogroups (A, C, Y, and W) may be prevented with available quadrivalent capsular polysaccharide-protein conjugate vaccines; these vaccines have been successfully implemented into immunization programs in the United States. Unfortunately, quadrivalent conjugate vaccines are not effective against serogroup B, now the most common cause of invasive meningococcal disease. Two recombinant protein vaccines recently were licensed for prevention of serogroup B disease. Recommendations for use of these serogroup B vaccines in the United States have been made by the Advisory Committee on Immunization Practices. This article will discuss all available meningococcal vaccines, current recommendations for use, lessons learned from previous experiences, and future considerations, with the hope of further understanding how use of these vaccines may help reduce incidence of meningococcal disease in the United States. PMID:27449147

  19. Implementation of proteomics for cancer research: past, present, and future.

    PubMed

    Karimi, Parisa; Shahrokni, Armin; Ranjbar, Mohammad R Nezami

    2014-01-01

    Cancer is the leading cause of the death, accounts for about 13% of all annual deaths worldwide. Many different fields of science are collaborating together studying cancer to improve our knowledge of this lethal disease, and find better solutions for diagnosis and treatment. Proteomics is one of the most recent and rapidly growing areas in molecular biology that helps understanding cancer from an omics data analysis point of view. The human proteome project was officially initiated in 2008. Proteomics enables the scientists to interrogate a variety of biospecimens for their protein contents and measure the concentrations of these proteins. Current necessary equipment and technologies for cancer proteomics are mass spectrometry, protein microarrays, nanotechnology and bioinformatics. In this paper, we provide a brief review on proteomics and its application in cancer research. After a brief introduction including its definition, we summarize the history of major previous work conducted by researchers, followed by an overview on the role of proteomics in cancer studies. We also provide a list of different utilities in cancer proteomics and investigate their advantages and shortcomings from theoretical and practical angles. Finally, we explore some of the main challenges and conclude the paper with future directions in this field. PMID:24761843

  20. The State of the Human Proteome in 2014/2015 as viewed through PeptideAtlas: enhancing accuracy and coverage through the AtlasProphet

    PubMed Central

    Deutsch, Eric W.; Sun, Zhi; Campbell, David; Kusebauch, Ulrike; Chu, Caroline S.; Mendoza, Luis; Shteynberg, David; Omenn, Gilbert S.; Moritz, Robert L.

    2016-01-01

    The Human PeptideAtlas is a compendium of the highest quality peptide identifications from over 1000 shotgun mass spectrometry proteomics experiments collected from many different labs, all reanalyzed through a uniform processing pipeline. The latest 2015-03 build contains substantially more input data than past releases, is mapped to a recent version of our merged reference proteome, and uses improved informatics processing and the development of the AtlasProphet to provide the highest quality results. Within the set of ~20,000 neXtProt primary entries, 14,070 (70%) are confidently detected in the latest build, 5% are ambiguous, 9% are redundant, leaving the total percentage of proteins for which there are no mapping detections at just 16% (3166), all derived from over 133 million peptide-spectrum matches identifying more than 1 million distinct peptides using AtlasProphet to characterize and classify the protein matches. Improved handling for detection and presentation of single amino-acid variants (SAAVs) reveals the detection of 5,326 uniquely mapping SAAVs across 2,794 proteins. With such a large amount of data, the control of false positives is a challenge. We present the methodology and results for maintaining rigorous quality, along with a discussion of the implications of the remaining sources of errors in the build. We check our uncertainty estimates against a set of olfactory receptor proteins not expected to be present in the set. We show how the use of synthetic reference spectra can provide confirmatory evidence for claims of detection of proteins with weak evidence. PMID:26139527

  1. Proteome Dynamics Reveals Pro-Inflammatory Remodeling of Plasma Proteome in a Mouse Model of NAFLD.

    PubMed

    Li, Ling; Bebek, Gurkan; Previs, Stephen F; Smith, Jonathan D; Sadygov, Rovshan G; McCullough, Arthur J; Willard, Belinda; Kasumov, Takhar

    2016-09-01

    Nonalcoholic fatty liver disease (NAFLD) is associated with an increased risk of cardiovascular disease. Because the liver is the major source of circulatory proteins, it is not surprising that hepatic disease could lead to alterations in the plasma proteome, which are therein implicated in atherosclerosis. The current study used low-density lipoprotein receptor-deficient (LDLR(-/-)) mice to examine the impact of Western diet (WD)-induced NAFLD on plasma proteome homeostasis. Using a (2)H2O-metabolic labeling method, we found that a WD led to a proinflammatory distribution of circulatory proteins analyzed in apoB-depleted plasma, which was attributed to an increased production. The fractional turnover rates of short-lived proteins that are implicated in stress-response, lipid metabolism, and transport functions were significantly increased with WD (P < 0.05). Pathway analyses revealed that alterations in plasma proteome dynamics were related to the suppression of hepatic PPARα, which was confirmed based on reduced gene and protein expression of PPARα in mice fed a WD. These changes were associated with ∼4-fold increase (P < 0.0001) in the proinflammatory property of apoB-depleted plasma. In conclusion, the proteome dynamics method reveals proinflammatory remodeling of the plasma proteome relevant to liver disease. The approach used herein may provide a useful metric of in vivo liver function and better enable studies of novel therapies surrounding NAFLD and other diseases. PMID:27439437

  2. Optimal control of gene expression for fast proteome adaptation to environmental change.

    PubMed

    Pavlov, Michael Y; Ehrenberg, Måns

    2013-12-17

    Bacterial populations growing in a changing world must adjust their proteome composition in response to alterations in the environment. Rapid proteome responses to growth medium changes are expected to increase the average growth rate and fitness value of these populations. Little is known about the dynamics of proteome change, e.g., whether bacteria use optimal strategies of gene expression for rapid proteome adjustments and if there are lower bounds to the time of proteome adaptation in response to growth medium changes. To begin answering these types of questions, we modeled growing bacteria as stoichiometrically coupled networks of metabolic pathways. These are balanced during steady-state growth in a constant environment but are initially unbalanced after rapid medium shifts due to a shortage of enzymes required at higher concentrations in the new environment. We identified an optimal strategy for rapid proteome adjustment in the absence of protein degradation and found a lower bound to the time of proteome adaptation after medium shifts. This minimal time is determined by the ratio between the Kullback-Leibler distance from the pre- to the postshift proteome and the postshift steady-state growth rate. The dynamics of optimally controlled proteome adaptation has a simple analytical solution. We used detailed numerical modeling to demonstrate that realistic bacterial control systems can emulate this optimal strategy for rapid proteome adaptation. Our results may provide a conceptual link between the physiology and population genetics of growing bacteria. PMID:24297927

  3. Pressurized Pepsin Digestion in Proteomics

    PubMed Central

    López-Ferrer, Daniel; Petritis, Konstantinos; Robinson, Errol W.; Hixson, Kim K.; Tian, Zhixin; Lee, Jung Hwa; Lee, Sang-Won; Tolić, Nikola; Weitz, Karl K.; Belov, Mikhail E.; Smith, Richard D.; Paša-Tolić, Ljiljana

    2011-01-01

    Integrated top-down bottom-up proteomics combined with on-line digestion has great potential to improve the characterization of protein isoforms in biological systems and is amendable to high throughput proteomics experiments. Bottom-up proteomics ultimately provides the peptide sequences derived from the tandem MS analyses of peptides after the proteome has been digested. Top-down proteomics conversely entails the MS analyses of intact proteins for more effective characterization of genetic variations and/or post-translational modifications. Herein, we describe recent efforts toward efficient integration of bottom-up and top-down LC-MS-based proteomics strategies. Since most proteomics separations utilize acidic conditions, we exploited the compatibility of pepsin (where the optimal digestion conditions are at low pH) for integration into bottom-up and top-down proteomics work flows. Pressure-enhanced pepsin digestions were successfully performed and characterized with several standard proteins in either an off-line mode using a Barocycler or an on-line mode using a modified high pressure LC system referred to as a fast on-line digestion system (FOLDS). FOLDS was tested using pepsin and a whole microbial proteome, and the results were compared against traditional trypsin digestions on the same platform. Additionally, FOLDS was integrated with a RePlay configuration to demonstrate an ultrarapid integrated bottom-up top-down proteomics strategy using a standard mixture of proteins and a monkey pox virus proteome. PMID:20627868

  4. Current capabilities of ``HPTAM'' for modeling high-temperature heat pipes' startup from a frozen state

    NASA Astrophysics Data System (ADS)

    Tournier, Jean-Michel; El-Genk, Mohamed

    2002-01-01

    The Heat Pipe Transient Analysis Model ``HPTAM'' has been developed at the University of New Mexico's Institute for Space and Nuclear Power Studies for simulating the transient and steady state operation as well as the startup of alkali-metal and low-temperature heat pipes from a frozen state. This model has been subject to continuous upgrade and verification since the early nineties using experimental data for water, sodium, and lithium heat pipes. Some of the current capabilities of HPTAM include tracking: (a) the progression of the 2-D thaw front in the wick and the transition fronts separating the successive flow regimes (free-molecular, transition, and continuum) in the vapor core; (b) the liquid circulation in the wick and in the annular space that may be incorporated by design between the wick and the heat pipe wall; (c) the formation of the wet point at the wick-vapor interface and its progression toward the condenser; (d) the excess liquid volume resulting from the decrease in density of the working fluid upon thaw and heating up to the operating temperature, and its accumulation at the end of the condenser section; (e) the change in the local radius of curvature of the liquid meniscus in the surface pores of the wick and incipient dryout; (f) the sublimation of the frozen working fluid in the evaporator and resolidification in the adiabatic and condenser sections early during the startup from a frozen state; and (g) the changes in the local vapor velocity and the liquid velocity and temperature distributions. The simulation capabilities of HPTAM are reviewed and examples of the code verification results using experimental data for the startup of sodium and lithium heat pipes from a frozen state are presented and discussed. HPTAM employs a very stable and efficient numerical technique and may run at twice the real time on a 700-MHz PC. .

  5. Landmark Report Analyzes Current State of U.S. Offshore Wind Industry (Fact Sheet)

    SciTech Connect

    Not Available

    2011-09-01

    New report assesses offshore wind industry, offshore wind resource, technology challenges, economics, permitting procedures, and potential risks and benefits. The National Renewable Energy Laboratory (NREL) recently published a new report that analyzes the current state of the offshore wind energy industry, Large-Scale Offshore Wind Power in the United States. It provides a broad understanding of the offshore wind resource, and details the associated technology challenges, economics, permitting procedures, and potential risks and benefits of developing this clean, domestic, renewable resource. The United States possesses large and accessible offshore wind energy resources. The availability of these strong offshore winds close to major U.S. coastal cities significantly reduces power transmission issues. The report estimates that U.S. offshore winds have a gross potential generating capacity four times greater than the nation's present electric capacity. According to the report, developing the offshore wind resource along U.S. coastlines and in the Great Lakes would help the nation: (1) Achieve 20% of its electricity from wind by 2030 - Offshore wind could supply 54 gigawatts of wind capacity to the nation's electrical grid, increasing energy security, reducing air and water pollution, and stimulating the domestic economy. (2) Provide clean power to its coastal demand centers - Wind power emits no carbon dioxide (CO2) and there are plentiful winds off the coasts of 26 states. (3) Revitalize its manufacturing sector - Building 54 GW of offshore wind energy facilities would generate an estimated $200 billion in new economic activity, and create more than 43,000 permanent, well-paid technical jobs in manufacturing, construction, engineering, operations and maintenance. NREL's report concludes that the development of the nation's offshore wind resources can provide many potential benefits, and with effective research, policies, and commitment, offshore wind energy can

  6. Proteomics and the Inner Ear

    PubMed Central

    Thalmann, Isolde

    2001-01-01

    The inner ear, one of the most complex organs, contains within its bony shell three sensory systems, the evolutionary oldest gravity receptor system, the three semicircular canals for the detection of angular acceleration, and the auditory system - unrivaled in sensitivity and frequency discrimination. All three systems are susceptible to a host of afflictions affecting the quality of life for all of us. In the first part of this review we present an introduction to the milestones of inner ear research to pave the way for understanding the complexities of a proteomics approach to the ear. Minute sensory structures, surrounded by large fluid spaces and a hard bony shell, pose extreme challenges to the ear researcher. In spite of these obstacles, a powerful preparatory technique was developed, whereby precisely defined microscopic tissue elements can be isolated and analyzed, while maintaining the biochemical state representative of the in vivo conditions. The second part consists of a discussion of proteomics as a tool in the elucidation of basic and pathologic mechanisms, diagnosis of disease, as well as treatment. Examples are the organ of Corti proteins OCP1 and OCP2, oncomodulin, a highly specific calcium-binding protein, and several disease entities, Meniere's disease, benign paroxysmal positional vertigo, and perilymphatic fistula. PMID:11790893

  7. Bioinformatic challenges in targeted proteomics.

    PubMed

    Reker, Daniel; Malmström, Lars

    2012-09-01

    Selected reaction monitoring mass spectrometry is an emerging targeted proteomics technology that allows for the investigation of complex protein samples with high sensitivity and efficiency. It requires extensive knowledge about the sample for the many parameters needed to carry out the experiment to be set appropriately. Most studies today rely on parameter estimation from prior studies, public databases, or from measuring synthetic peptides. This is efficient and sound, but in absence of prior data, de novo parameter estimation is necessary. Computational methods can be used to create an automated framework to address this problem. However, the number of available applications is still small. This review aims at giving an orientation on the various bioinformatical challenges. To this end, we state the problems in classical machine learning and data mining terms, give examples of implemented solutions and provide some room for alternatives. This will hopefully lead to an increased momentum for the development of algorithms and serve the needs of the community for computational methods. We note that the combination of such methods in an assisted workflow will ease both the usage of targeted proteomics in experimental studies as well as the further development of computational approaches. PMID:22866949

  8. State Spending for Higher Education in the Next Decade: The Battle To Sustain Current Support.

    ERIC Educational Resources Information Center

    Hovey, Harold A.

    This report addresses the future financing of higher education, focusing primarily on the states and presenting state-by-state data on important trends. It assesses the outlook for state finances, and, in the context of the ongoing needs of other major state services, for state support of higher education. In examining the forecast of state and…

  9. Fe, O, and C Charge States Associated with Quiescent Versus Active Current Sheets in the Solar Wind

    NASA Technical Reports Server (NTRS)

    Suess, S. T.; Ko, Y.-K.; vonSteiger, R.

    2008-01-01

    Ulysses MAG data were used to locate the heliospheric current sheet in data from 1991 through 2006. The purpose was to characterize typical charge states for Fe, O, and C in the vicinity of the current sheet and provide insight into the physical sources for these charge states in the corona. A study of He/H around the current sheets has led to a clear distinction between quiescent current sheets at times of low solar activity and active current sheets associated with magnetic clouds (and, presumably, ICMES). It has been shown that high ionization state Fe is produced in the corona in current sheets associated with CMEs through spectroscopic observations of the corona and through in situ detection at Ulysses. Here we show that the ionization state of Fe is typically only enhanced around active current sheets while the ionization states of O and C are commonly enhanced around both quiescent and active current sheets. This is consistent with UV coronal spectroscopy, which has shown that reconnection in current sheets behind CMEs leads to high temperatures not typically seen above quiet streamers.

  10. Cysteines under ROS attack in plants: a proteomics view.

    PubMed

    Akter, Salma; Huang, Jingjing; Waszczak, Cezary; Jacques, Silke; Gevaert, Kris; Van Breusegem, Frank; Messens, Joris

    2015-05-01

    Plants generate reactive oxygen species (ROS) as part of their metabolism and in response to various external stress factors, potentially causing significant damage to biomolecules and cell structures. During the course of evolution, plants have adapted to ROS toxicity, and use ROS as signalling messengers that activate defence responses. Cysteine (Cys) residues in proteins are one of the most sensitive targets for ROS-mediated post-translational modifications, and they have become key residues for ROS signalling studies. The reactivity of Cys residues towards ROS, and their ability to react to different oxidation states, allow them to appear at the crossroads of highly dynamic oxidative events. As such, a redox-active cysteine can be present as S-glutathionylated (-SSG), disulfide bonded (S-S), sulfenylated (-SOH), sulfinylated (-SO2H), and sulfonylated (-SO3H). The sulfenic acid (-SOH) form has been considered as part of ROS-sensing pathways, as it leads to further modifications which affect protein structure and function. Redox proteomic studies are required to understand how and why cysteines undergo oxidative post-translational modifications and to identify the ROS-sensor proteins. Here, we update current knowledge of cysteine reactivity with ROS. Further, we give an overview of proteomic techniques that have been applied to identify different redox-modified cysteines in plants. There is a particular focus on the identification of sulfenylated proteins, which have the potential to be involved in plant signal transduction. PMID:25750420

  11. Current State of Pain Care for Hospitalized Patients at End of Life

    PubMed Central

    Yao, Yingwei; Keenan, Gail; Al-Masalha, Fadi; Lopez, Karen Dunn; Khokar, Ashfaq; Johnson, Andrew; Ansari, Rashid; Wilkie, Diana J.

    2013-01-01

    We report findings on the current state of pain care in hospitals for end-of-life (EOL) patients using longitudinal data from eight diverse medical-surgical units located in 4 different Midwestern hospitals over 24 months. We identified 1,425 EOL care episodes, 596 (41.3%) of which had a pain diagnosis. The percentage of EOL patients with pain varied significantly across units (p<.001), and was even lower (27.7%) for those with “acute confusion.” Additionally, 30% of EOL patients had severe or significant pain at death or discharge to hospice and only 42.7% actually met the expected pain related outcome ratings. Pain often improved within 48 hours of admission (p<.005), the improvement, however, stagnated following this initial time period (p=.92). A sizable gap between pain science and clinical practice continues. PMID:22556281

  12. High current, low emittance, steady state electron guns with plasma cathodes

    SciTech Connect

    Hershcovitch, A.

    1995-12-31

    Major limitations of plasma cathodes have been overcome in an electron gun based on extraction of superthermal electrons from a discharge characterized by a large component of high energy electrons with a low thermal spread. A grid is employed to select these electrons for extraction while retaining the bulk electrons in the discharge. Steady state extraction of electron beams corresponding to over 60% of the total arc discharge current has been observed. A perveance of over 280 microperv was reached with the extraction of 9A at 1 keV from a 6 nun aperture. Some of the characteristics of the electron beam described in this paper are very attractive for electron beam melting.

  13. Nanomaterials in plant protection and fertilization: current state, foreseen applications, and research priorities.

    PubMed

    Gogos, Alexander; Knauer, Katja; Bucheli, Thomas D

    2012-10-01

    Scientific publications and patents on nanomaterials (NM) used in plant protection or fertilizer products have exponentially increased since the millennium shift. While the United States and Germany have published the highest number of patents, Asian countries released most scientific articles. About 40% of all contributions deal with carbon-based NM, followed by titanium dioxide, silver, silica, and alumina. Nanomaterials come in many diverse forms (surprisingly often ≫100 nm), from solid doped particles to (often nonpersistent) polymer and oil-water based structures. Nanomaterials serve equally as additives (mostly for controlled release) and active constituents. Product efficiencies possibly increased by NM should be balanced against enhanced environmental NM input fluxes. The dynamic development in research and its considerable public perception are in contrast with the currently still very small number of NM-containing products on the market. Nanorisk assessment and legislation are largely in their infancies. PMID:22963545

  14. Public health services and systems research: current state of finance research.

    PubMed

    Ingram, Richard C; Bernet, Patrick M; Costich, Julia F

    2012-11-01

    There is a growing recognition that the US public health system should strive for efficiency-that it should determine the optimal ways to utilize limited resources to improve and protect public health. The field of public health finance research is a critical part of efforts to understand the most efficient ways to use resources. This article discusses the current state of public health finance research through a review of public health finance literature, chronicles important lessons learned from public health finance research to date, discusses the challenges faced by those seeking to conduct financial research on the public health system, and discusses the role of public health finance research in relation to the broader endeavor of Public Health Services and Systems Research. PMID:23023275

  15. [Cell engineering in the treatment of diabetes mellitus: current state and prospectives].

    PubMed

    Nagibovich, O A; Golota, A S; Krassii, A B

    2016-04-01

    The article is dedicated to the current state and prospectives of cell engineering in the treatment of diabetes mellitus. The material is based on the analysis of clinical trials in which cell engineering has been applied for the treatment of diabetes mellitus and its complications. It has been shown that despite the decade of intensive research the clinically significant results have not been achieved yet. At the same time the fast growth of the number of publications in the field testified to intensity of basic and applied research and the large quantity of ongoing clinical trials on the topic make it possible to. look at the prospectives of the employment of cell engineering in the treatment of diabetes mellitus with a certain optimism. PMID:27416722

  16. Automatic liquid handling for life science: a critical review of the current state of the art.

    PubMed

    Kong, Fanwei; Yuan, Liang; Zheng, Yuan F; Chen, Weidong

    2012-06-01

    Liquid handling plays a pivotal role in life science laboratories. In experiments such as gene sequencing, protein crystallization, antibody testing, and drug screening, liquid biosamples frequently must be transferred between containers of varying sizes and/or dispensed onto substrates of varying types. The sample volumes are usually small, at the micro- or nanoliter level, and the number of transferred samples can be huge when investigating large-scope combinatorial conditions. Under these conditions, liquid handling by hand is tedious, time-consuming, and impractical. Consequently, there is a strong demand for automated liquid-handling methods such as sensor-integrated robotic systems. In this article, we survey the current state of the art in automatic liquid handling, including technologies developed by both industry and research institutions. We focus on methods for dealing with small volumes at high throughput and point out challenges for future advancements. PMID:22357568

  17. The LandScan Global Population Distribution Project: Current State of the Art and Prospective Innovation

    SciTech Connect

    Rose, Amy N; Bright, Eddie A

    2014-01-01

    Advances in remote sensing, dasymetric mapping techniques, and the ever-increasing availability of spatial datasets have enhanced global human population distribution databases. These datasets demonstrate an enormous improvement over the conventional use of choropleth maps to represent population distribution and are vital for analysis and planning purposes including humanitarian response, disease mapping, risk analysis, and evacuation modeling. Dasymetric mapping techniques have been employed to address spatial mismatch, but also to develop finer resolution population distributions in areas of the world where subnational census data are coarse or non-existent. One such implementation is the LandScan Global model which provides a 30 arc-second global population distribution based on ancillary datasets such as land cover, slope, proximity to roads, and settlement locations. This work will review the current state of the LandScan model, future innovations aimed at increasing spatial and demographic resolution, and situate LandScan within the landscape of other global population distribution datasets.

  18. Transcranial direct current stimulation of the motor cortex in waking resting state induces motor imagery.

    PubMed

    Speth, Jana; Speth, Clemens; Harley, Trevor A

    2015-11-01

    This study investigates if anodal and cathodal transcranial direct current stimulation (tDCS) of areas above the motor cortex (C3) influences spontaneous motor imagery experienced in the waking resting state. A randomized triple-blinded design was used, combining neurophysiological techniques with tools of quantitative mentation report analysis from cognitive linguistics. The results indicate that while spontaneous motor imagery rarely occurs under sham stimulation, general and athletic motor imagery (classified as athletic disciplines), is induced by anodal tDCS. This insight may have implications beyond basic consciousness research. Motor imagery and corresponding motor cortical activation have been shown to benefit later motor performance. Electrophysiological manipulations of motor imagery could in the long run be used for rehabilitative tDCS protocols benefitting temporarily immobile clinical patients who cannot perform specific motor imagery tasks - such as dementia patients, infants with developmental and motor disorders, and coma patients. PMID:26204566

  19. Engineering Ethics Education : Its Necessity, Objectives, Methods, Current State, and Challenges

    NASA Astrophysics Data System (ADS)

    Fudano, Jun

    The importance of engineering ethics education has become widely recognized in the industrialized countries including Japan. This paper examines the background against which engineering ethics education is required, and reviews its objectives, methods, and challenges, as well as its current state. In pointing out important issues associated with the apparent acceptance and quantitative development of ethics education, especially after the establishment of the Japan Accreditation Board for Engineering Education in 1999, the author stresses that the most serious problem is the lack of common understanding on the objectives of engineering ethics education. As a strategy to improve the situation, the so-called “Ethics-across-the-Curriculum” approach is introduced. The author also claims that business/organization ethics which is consistent with engineering ethics should be promoted in Japan.

  20. Nonequilibrium current-carrying steady states in the anisotropic X Y spin chain

    NASA Astrophysics Data System (ADS)

    Lancaster, Jarrett L.

    2016-05-01

    Out-of-equilibrium behavior is explored in the one-dimensional anisotropic X Y model. Initially preparing the system in the isotropic X X model with a linearly varying magnetic field to create a domain-wall magnetization profile, dynamics is generated by rapidly changing the exchange interaction anisotropy and external magnetic field. Relaxation to a nonequilibrium steady state is studied analytically at the critical transverse Ising point, where correlation functions may be computed in closed form. For arbitrary values of anisotropy and external field, an effective generalized Gibbs' ensemble is shown to accurately describe observables in the long-time limit. Additionally, we find spatial oscillations in the exponentially decaying, transverse spin-spin correlation functions with wavelength set by the magnetization jump across the initial domain wall. This wavelength depends only weakly on anisotropy and magnetic field in contrast to the current, which is highly dependent on these parameters.

  1. ICD-9 to ICD-10: evolution, revolution, and current debates in the United States.

    PubMed

    Topaz, Maxim; Shafran-Topaz, Leah; Bowles, Kathryn H

    2013-01-01

    The International Statistical Classification of Diseases and Related Health Problems (ICD) has undergone a long evolution from its initial inception in the late 18th century. Today, ICD is the internationally recognized classification that helps clinicians, policy makers, and patients to navigate, understand, and compare healthcare systems and services. Currently in the United States, hot debates surround the transition from the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) to the International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM). This article presents an analysis of the views of the proponents and opponents of the upcoming change. We also briefly present and analyze the quality of the most frequently cited scientific evidence that underpins the recent debates focusing on two major issues: ICD-10-CM implementation costs and revenue gains and the projected clinical data quality improvement. We conclude with policy and research suggestions for healthcare stakeholders. PMID:23805064

  2. Sixty years of fear appeal research: current state of the evidence.

    PubMed

    Ruiter, Robert A C; Kessels, Loes T E; Peters, Gjalt-Jorn Y; Kok, Gerjo

    2014-04-01

    Fear arousal is widely used in persuasive campaigns and behavioral change interventions. Yet, experimental evidence argues against the use of threatening health information. The authors reviewed the current state of empirical evidence on the effectiveness of fear appeals. Following a brief overview of the use of fear arousal in health education practice and the structure of effective fear appeals according to two main theoretical frameworks-protection motivation theory and the extended parallel process model-the findings of six meta-analytic studies in the effectiveness of fear appeals are summarized. It is concluded that coping information aimed at increasing perceptions of response effectiveness and especially self-efficacy is more important in promoting protective action than presenting threatening health information aimed at increasing risk perceptions and fear arousal. Alternative behavior change methods than fear appeals should be considered. PMID:24811876

  3. Aerospace Concurrent Engineering Design Teams: Current State, Next Steps and a Vision for the Future

    NASA Technical Reports Server (NTRS)

    Hihn, Jairus; Chattopadhyay, Debarati; Karpati, Gabriel; McGuire, Melissa; Borden, Chester; Panek, John; Warfield, Keith

    2011-01-01

    Over the past sixteen years, government aerospace agencies and aerospace industry have developed and evolved operational concurrent design teams to create novel spaceflight mission concepts and designs. These capabilities and teams, however, have evolved largely independently. In today's environment of increasingly complex missions with limited budgets it is becoming readily apparent that both implementing organizations and today's concurrent engineering teams will need to interact more often than they have in the past. This will require significant changes in the current state of practice. This paper documents the findings from a concurrent engineering workshop held in August 2010 to identify the key near term improvement areas for concurrent engineering capabilities and challenges to the long-term advancement of concurrent engineering practice. The paper concludes with a discussion of a proposed vision for the evolution of these teams over the next decade.

  4. Review of the Current State of Knowledge on the Effects of Radiation on Concrete

    DOE PAGESBeta

    Rosseel, Thomas M.; Maruyama, Ippei; Le Pape, Yann; Kontani, Osamu; Giorla, Alain B.; Remec, Igor; Wall, James J.; Sircar, Madhumita; Andrade, Carmen; Ordonez, Manuel

    2016-07-01

    A review of the current state of knowledge on the effects of radiation on concrete in nuclear applications is presented. Emphasis is placed on the effects of radiation damage as reflected by changes in engineering properties of concrete in the evaluation of the long-term operation (LTO) and for Plant Life or Aging Management of nuclear power plants (NPPs) in Japan, Spain, and the United States. National issues and concerns are described for Japan and the US followed by a discussion of the fundamental understanding of the effects radiation on concrete. Specifically, the effects of temperature, moisture content, and irradiation onmore » ordinary Portland cement paste and the role of temperature and neutron energy spectra on radiation induced volumetric expansion (RIVE) of aggregate-forming minerals are described. This is followed by a discussion of the bounding conditions for extended operation, the significance of accelerated irradiation conditions, the role of temperature, creep, and how these issues are being incorporated into numerical and meso-scale models. From these insights on radiation damage, analyses of these effects on concrete structures are reviewed and the current status of work in Japan and the US are described. Also discussed is the recent formation of a new international scientific and technical organization, the International Committee on Irradiated Concrete (ICIC), to provide a forum for timely information exchanges among organizations pursuing the identification, quantification, and modeling of the effects of radiation on concrete in commercial nuclear applications. Lastly, the paper concludes with a discussion of research gaps including: 1) interpreting test-reactor data, 2) evaluating service-irradiated concrete for aging management and to inform radiation damage models with the Zorita NPP (Spain) serving as the first comprehensive test case, 3) irradiated-assisted alkali-silica reactions, and 4) RIVE under constrained conditions.« less

  5. Brain-Computer Interfaces Using Sensorimotor Rhythms: Current State and Future Perspectives

    PubMed Central

    Yuan, Han; He, Bin

    2014-01-01

    Many studies over the past two decades have shown that people can use brain signals to convey their intent to a computer using brain-computer interfaces (BCIs). BCI systems extract specific features of brain activity and translate them into control signals that drive an output. Recently, a category of BCIs that are built on the rhythmic activity recorded over the sensorimotor cortex, i.e. the sensorimotor rhythm (SMR), has attracted considerable attention among the BCIs that use noninvasive neural recordings, e.g. electroencephalography (EEG), and have demonstrated the capability of multi-dimensional prosthesis control. This article reviews the current state and future perspectives of SMR-based BCI and its clinical applications, in particular focusing on the EEG SMR. The characteristic features of SMR from the human brain are described and their underlying neural sources are discussed. The functional components of SMR-based BCI, together with its current clinical applications are reviewed. Lastly, limitations of SMR-BCIs and future outlooks are also discussed. PMID:24759276

  6. Measurements of the normal state persistent current in Au rings at high and low magnetic fields

    NASA Astrophysics Data System (ADS)

    Petkovic, Ivana; Ngo, Dustin; Lollo, Anthony; Harris, Jack

    2014-03-01

    Flux biased normal metal rings smaller than the phase coherence length can sustain persistent current (PC). We employ cantilever torque magnetometry to detect PC with high sensitivity, efficient background rejection, and in an electromagnetically clean environment. Previously, our group focused on the high magnetic field regime, where the PC is well described by single-particle theory. However at low magnetic field (few flux quanta) interaction effects are expected to be dominant. Previous low field studies by other groups employing SQUID and resonator-based techniques have found that Au, Ag, Cu, and GaAs rings show a large diamagnetic average PC, indicative of attractive e-e interactions. One possible explanation is that the superconductivity that would normally arise from this interaction is suppressed by a small number of magnetic impurities (~ 1 ppm), while the interaction-enhanced persistent current is not. In this talk we will describe measurements of Au rings. We have fabricated arrays of 100,000 rings with 125 nm radius on ultrasensitive silicon cantilevers. At high magnetic fields, we find that the PC agrees with single-particle theory. We also describe the results at low field, expected to give further insight into the many body ground state of this system. We gratefully acknowledge support from NSF Grant #1205861.

  7. Simulations of fast-wave current drive in pulsed and steady-state DEMO designs

    NASA Astrophysics Data System (ADS)

    Bilato, R.; Brambilla, M.; Fable, E.

    2014-11-01

    Electromagnetic waves in the ion-cyclotron (IC) range of frequencies are presently investigated as possible current drive (CD) systems in fusion reactors. Among many physical and technical issues, an accurate description of radio-frequency (RF) power absorption by fusion- born alpha particles is of special importance, since RF heating of these particles is not only detrimental for the CD efficiency, but might worsen the operative conditions by increasing their prompt losses. The capability of the full-wave TORIC code has been recently augmented to account for RF absorption by fusion-born alpha particles, calculated to all-orders in finite Larmor radius and with a realistic distribution function. Here, we present simulation with TORIC addressing the sensitivity of current drive efficiency on the design of a future reactor, in particular density and temperature profiles, magnetic field intensity, and plasma dimensions. For this purpose, we have investigated possible frequency windows for CD for two proposed versions of the DEMO reactor, namely its pulsed and its more ambitious steady-state design. The important role of the antenna for a realistic estimate of the CD efficiency is pointed out.

  8. “Seed Proteomics"

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Proteomic analysis of seeds encounters some specific problems that do not impinge on analyses of other plant cells, tissues, or organs. There are anatomic considerations. Seeds comprise the seed coat, the storage organ(s), and the embryonic axis. Are these to be studied individually or as a compo...

  9. Developing the wool proteome.

    PubMed

    Clerens, Stefan; Cornellison, Charisa D; Deb-Choudhury, Santanu; Thomas, Ancy; Plowman, Jeffrey E; Dyer, Jolon M

    2010-08-01

    The wool proteome has been largely uncharted due to a lack of database coverage, poor protein extractability and dynamic range issues. Yet, investigating correlations between wool physical properties and protein content, or characterising UV-, heat- or processing-induced protein damage requires the availability of an identifiable and identified proteome. In this study we have achieved unprecedented wool proteome identification through a strategy of comprehensive data acquisition, iterative protein identification/validation and concurrent augmentation of the sequence database. Data acquisition comprised a range of different hyphenated MS techniques including LC-MS/MS, LC-MALDI, 2D-LC-MS/MS and SDS-PAGE LC-MS. Using iterative searching of databases and search result combination using ProteinScape, a systematic expansion of identifiable proteins in the sequence database was achieved. This was followed by extensive validation and rationalisation of the protein identifications. In total, 72 complete and 30 partial ovine-specific protein sequences were added to the database, and 113 wool proteins were identified. Enhanced access to ovine-specific protein identification and characterisation will facilitate all wool fibre protein chemistry and proteomics research. PMID:20478423

  10. Arabidopsis peroxisome proteomics

    PubMed Central

    Bussell, John D.; Behrens, Christof; Ecke, Wiebke; Eubel, Holger

    2013-01-01

    The analytical depth of investigation of the peroxisomal proteome of the model plant Arabidopsis thaliana has not yet reached that of other major cellular organelles such as chloroplasts or mitochondria. This is primarily due to the difficulties associated with isolating and obtaining purified samples of peroxisomes from Arabidopsis. So far only a handful of research groups have been successful in obtaining such fractions. To make things worse, enriched peroxisome fractions frequently suffer from significant organellar contamination, lowering confidence in localization assignment of the identified proteins. As with other cellular compartments, identification of peroxisomal proteins forms the basis for investigations of the dynamics of the peroxisomal proteome. It is therefore not surprising that, in terms of functional analyses by proteomic means, peroxisomes are lagging considerably behind chloroplasts or mitochondria. Alternative strategies are needed to overcome the obstacle of hard-to-obtain organellar fractions. This will help to close the knowledge gap between peroxisomes and other organelles and provide a full picture of the physiological pathways shared between organelles. In this review, we briefly summarize the status quo and discuss some of the methodological alternatives to classic organelle proteomic approaches. PMID:23630535

  11. Progress toward steady-state tokamak operation exploiting the high bootstrap current fraction regime

    NASA Astrophysics Data System (ADS)

    Ren, Q. L.; Garofalo, A. M.; Gong, X. Z.; Holcomb, C. T.; Lao, L. L.; McKee, G. R.; Meneghini, O.; Staebler, G. M.; Grierson, B. A.; Qian, J. P.; Solomon, W. M.; Turnbull, A. D.; Holland, C.; Guo, W. F.; Ding, S. Y.; Pan, C. K.; Xu, G. S.; Wan, B. N.

    2016-06-01

    Recent DIII-D experiments have increased the normalized fusion performance of the high bootstrap current fraction tokamak regime toward reactor-relevant steady state operation. The experiments, conducted by a joint team of researchers from the DIII-D and EAST tokamaks, developed a fully noninductive scenario that could be extended on EAST to a demonstration of long pulse steady-state tokamak operation. Improved understanding of scenario stability has led to the achievement of very high values of βp and βN , despite strong internal transport barriers. Good confinement has been achieved with reduced toroidal rotation. These high βp plasmas challenge the energy transport understanding, especially in the electron energy channel. A new turbulent transport model, named TGLF-SAT1, has been developed which improves the transport prediction. Experiments extending results to long pulse on EAST, based on the physics basis developed at DIII-D, have been conducted. More investigations will be carried out on EAST with more additional auxiliary power to come online in the near term.

  12. Current-carrying quasi-steady states in a periodically driven many-body system

    NASA Astrophysics Data System (ADS)

    Rudner, Mark; Lindner, Netanel; Berg, Erez

    We investigate many-body dynamics in a one-dimensional interacting periodically driven system, based on a partially-filled version of Thouless's topologically quantized adiabatic pump. The corresponding single particle Floquet bands are chiral, with the Floquet spectrum realizing nontrivial cycles around the quasienergy Brillouin zone. For non-integer filling the system is gapless; here the driving cannot be adiabatic and the system is expected to rapidly absorb energy from the driving field. We identify parameter regimes where scattering between Floquet bands of opposite chirality is exponentially suppressed, opening a long time window where the many-body evolution separately conserves the occupations of the two chiral bands. Within this intermediate time regime we predict that the system reaches a quasi-steady state with uniform crystal momentum occupation within each Floquet band. This state furthermore carries a non-vanishing current given directly by the difference of densities in the right and left moving chiral bands. This remarkable behavior, which holds for both bosons and fermions, may be readily studied experimentally in recently developed cold atom systems.

  13. Current state and prospects of researches on the control of turbulent boundary layer by air blowing

    NASA Astrophysics Data System (ADS)

    Kornilov, V. I.

    2015-07-01

    The paper presents the analytical review of the current state of the investigations and development trends on the problem of turbulent friction and aerodynamic drag reduction in simple model configurations, which is among key ones in modern aeromechanics. Under consideration is the modern fast progressing method of the turbulent flow control by air- and other gases (micro)blowing through a permeable surface, which is utilized in incompressible and compressible turbulent boundary layers. Several computational results to understand the essential flow physics are also included. The problem of simulation of the flow over a perforated wall where some ambiguities, in particular, at the permeable/impermeable boundary being still remained is discussed. Special attention is paid to the analysis of most important experimental and numerical results obtained with the air blowing through a finely-perforated surface, analysis of the physical peculiarities and regularities of the flow with the blowing, probability to describe the properties of such a flow within simple approach frameworks, evaluation of the efficiency of this control method, as well as the trends and opportunities of this method progress in view of state-of-the-art achievements. Although this technology has a penalty for developing the effective turbulent-flow control method, some modifications of the air blowing are an attractive alternative for real applications.

  14. Patient and citizen participation in German health care--current state and future perspectives.

    PubMed

    Loh, Andreas; Simon, Daniela; Bieber, Christiane; Eich, Wolfgang; Härter, Martin

    2007-01-01

    Patient participation within the German healthcare system is described at three different levels: the macro level as active patient influence on the regulation of medical care, the meso level in terms of institutions enhancing patient information and counselling, and the micro level focusing on the actual treatment decision-making process in the medical encounter. The main focus of the present publication is on the health care system-specific influences on patient participation in medical decision-making and on the current state of research and implementation of shared decision-making in Germany. We describe institutions promoting patient involvement, their aims and initiatives as well as recent changes in German legislation. Against the background of German health politics' endorsement of patient participation the German Ministry of Health funded a research consortium with shared decision-making intervention projects in various disease areas. The present state of the intervention projects' results is outlined as well as subsequently funded transfer projects and future perspectives of research grants. Supported by health politics and the utilisation of scientific evidence shared decision-making's transfer into practice is considered to be relevant to the German health care system. PMID:17601177

  15. Current status of solid waste management in small island developing states: A review

    SciTech Connect

    Mohee, Romeela; Mauthoor, Sumayya; Bundhoo, Zumar M.A.; Somaroo, Geeta; Soobhany, Nuhaa; Gunasee, Sanjana

    2015-09-15

    Highlights: • Waste management is a matter of great concern for small island developing states. • On average, waste generation rate in these islands amounts to 1.29 kg/capita/day. • Illegal dumping and landfilling prevail in most small island developing states. • Sustainable waste management practices, previously absent, are now emerging. • However, many challenges still hinder the implementation of these practices. - Abstract: This article reviews the current status of waste management in Small Island Developing States (SIDS) and the challenges that are faced in solid waste management. The waste generation rates of SIDS were compared within the three geographic regions namely Caribbean SIDS, Pacific SIDS and Atlantic, Indian Ocean, Mediterranean and South China (AIMS) SIDS and with countries of the Organisation for Economic Co-Operation and Development (OECD). Only Pacific SIDS had a waste generation rate less than 1 kg/capita/day. The waste generation rates for the three SIDS regions averaged 1.29 kg/capita/day while that for OECD countries was at a mean value of 1.35 kg/capita/day. The waste compositions in the different SIDS regions were almost similar owing to comparable consumption patterns while these differed to a large extent with wastes generated in OECD countries. In SIDS, the major fraction of MSW comprised of organics (44%) followed by recyclables namely paper, plastics, glass and metals (total: 43%). In contrast, MSW in OECD countries consisted mainly of recyclables (43%) followed by organics (37%). This article also reviewed the other functional elements of the waste management systems in SIDS. Several shortcomings were noted in the process of waste collection, transfer and transport namely the fact of having outdated collection vehicles and narrow roads which are inaccessible. Among the waste management practices in SIDS, waste disposal via landfilling, illegal dumping and backyard burning were favoured most of the time at the expense of

  16. Omics on bioleaching: current and future impacts.

    PubMed

    Martinez, Patricio; Vera, Mario; Bobadilla-Fazzini, Roberto A

    2015-10-01

    Bioleaching corresponds to the microbial-catalyzed process of conversion of insoluble metals into soluble forms. As an applied biotechnology globally used, it represents an extremely interesting field of research where omics techniques can be applied in terms of knowledge development, but moreover in terms of process design, control, and optimization. In this mini-review, the current state of genomics, proteomics, and metabolomics of bioleaching and the major impacts of these analytical methods at industrial scale are highlighted. In summary, genomics has been essential in the determination of the biodiversity of leaching processes and for development of conceptual and functional metabolic models. Proteomic impacts are mostly related to microbe-mineral interaction analysis, including copper resistance and biofilm formation. Early steps of metabolomics in the field of bioleaching have shown a significant potential for the use of metabolites as industrial biomarkers. Development directions are given in order to enhance the future impacts of the omics in biohydrometallurgy. PMID:26278538

  17. Experimental and numerical characterization of sea-state and coastal currents close to the Giglio island.

    NASA Astrophysics Data System (ADS)

    Brandini, Carlo; Taddei, Stefano; Doronzo, Bartolomeo; Costanza, Letizia; Fattorini, Maria; Serafino, Francesco; Ludeno, Giovanni; Ciarravano, Alessandro

    2015-04-01

    The study of sub-mesoscale circulation phenomena in coastal areas is complicated by the high resolution requested for both the observation and the simulation of such currents, and by the difficulty of appropriately validating the remote sensing and the numerical data. In this work we present the results of a long period of waves and coastal currents observations, produced by the X-band radar that was implemented in 2012 at the Giglio Island, after the accident of the Costa Concordia ship. The radar installation has allowed to verify the structure of particular sea states and hydrodynamic phenomena that can be reproduced also by means of some numerical models implemented in the area: in particular, SWAN for waves prediction, and ROMS for coastal circulation . The models were configured through multiple nesting in order to reach resolutions comparable to coastal radar observations. The measurements have been validated independently through the use of drifters in experimental campaigns around the island. The complete view of the 2D spectrum, as recorded by the radar, allowed to fully characterize sea states with crossed-seas and also coastal refraction phenomena (due to the southwest sea that turns all around the island), diffracted and even reflected wave patterns (Ludeno et al., 2014). The circulation phenomena are even more complex, as they are produced by a combination of local forcing conditions and tides, and by the interaction of the large-scale circulation with the local conformation of the bathymetry and the coastline. Circulation cells have been often observed, even in the form of a double-gyre configuration, also due to the non-stationarity of the atmospheric forcing and to multiple interaction effects. In our work we attempt to reproduce some of these phenomena, which are difficult to model also for their inherent non-linearity. We have considered the use of the native ROMS algorithm for multiple nested domains, by implementing it up to 50 m resolution

  18. Defining the Boundaries and Characterizing the Landscape of Genome Expression in Vascular Tissues of Populus using Shotgun Proteomics

    SciTech Connect

    Abraham, Paul E; Adams, Rachel M; Giannone, Richard J; Kalluri, Udaya C; Ranjan, Priya; Erickson, Brian K; Shah, Manesh B; Tuskan, Gerald A; Hettich, Robert {Bob} L

    2012-01-01

    Current state-of-the-art experimental and computational proteomic approaches were integrated to obtain a comprehensive protein profile of Populus vascular tissue. This featured: 1) a large sample set consisting of two genotypes grown under normal and tension stress conditions, 2) bioinformatics clustering to effectively handle gene duplication, and 3) an informatics approach to track and identify single amino acid polymorphisms (SAAPs). By applying a clustering algorithm to the Populus database, the number of protein entries decreased from 64,689 proteins to a total of 43,069 protein groups, thereby reducing 7,505 identified proteins to a total of 4,226 protein groups, in which 2,016 were singletons. This reduction implies that ~50% of the measured proteins were clustered into groups that shared extensive sequence homology. Using conservative search criteria, we were able to identify 1,354 peptides containing a SAAP and 201 peptides that become tryptic due to a K or R substitution. These newly identified peptides correspond to 502 proteins, including 97 proteins that were not previously identified. In total, the integration of deep proteome measurements on an extensive sample set with protein clustering and peptide sequence variants provided an unprecedented level of proteome characterization for Populus, allowing us to spatially resolve the vascular tissue proteome.

  19. Proteomics of effector-triggered immunity (ETI) in plants

    PubMed Central

    Hurley, Brenden; Subramaniam, Rajagopal; Guttman, David S; Desveaux, Darrell

    2014-01-01

    Effector-triggered immunity (ETI) was originally termed gene-for-gene resistance and dates back to fundamental observations of flax resistance to rust fungi by Harold Henry Flor in the 1940s. Since then, genetic and biochemical approaches have defined our current understanding of how plant “resistance” proteins recognize microbial effectors. More recently, proteomic approaches have expanded our view of the protein landscape during ETI and contributed significant advances to our mechanistic understanding of ETI signaling. Here we provide an overview of proteomic techniques that have been used to study plant ETI including both global and targeted approaches. We discuss the challenges associated with ETI proteomics and highlight specific examples from the literature, which demonstrate how proteomics is advancing the ETI research field. PMID:25513776

  20. A Biologist's Field Guide to Multiplexed Quantitative Proteomics.

    PubMed

    Bakalarski, Corey E; Kirkpatrick, Donald S

    2016-05-01

    High-throughput genomic and proteomic studies have generated near-comprehensive catalogs of biological constituents within many model systems. Nevertheless, static catalogs are often insufficient to fully describe the dynamic processes that drive biology. Quantitative proteomic techniques address this need by providing insight into closely related biological states such as the stages of a therapeutic response or cellular differentiation. The maturation of quantitative proteomics in recent years has brought about a variety of technologies, each with their own strengths and weaknesses. It can be difficult for those unfamiliar with this evolving landscape to match the experiment at hand with the best tool for the job. Here, we outline quantitative methods for proteomic mass spectrometry and discuss their benefits and weaknesses from the perspective of the biologist aiming to generate meaningful data and address mechanistic questions. PMID:26873251

  1. Shotgun proteomics of bacterial pathogens: advances, challenges and clinical implications.

    PubMed

    Semanjski, Maja; Macek, Boris

    2016-02-01

    Mass spectrometry-based proteomics is increasingly used in analysis of bacterial pathogens. Simple experimental set-ups based on high accuracy mass spectrometry and powerful biochemical and bioinformatics tools are capable of reliably quantifying levels of several thousand bacterial proteins in a single experiment, reaching the analytical capacity to completely map whole proteomes. Here the authors present the state-of-the-art in bacterial pathogen proteomics and discuss challenges that the field is facing, especially in analysis of low abundant, modified proteins from organisms that are difficult to culture. Constant improvements in speed and sensitivity of mass spectrometers, as well as in bioinformatic and biochemical workflows will soon allow for comprehensive analysis of regulatory mechanisms of pathogenicity and enable routine application of proteomics in the clinical setting. PMID:26653908

  2. Implementing the Common Core State Standards for Mathematics: A Comparison of Current District Content in 41 States. Working Paper #32

    ERIC Educational Resources Information Center

    Cogan, Leland; Schmidt, William; Houang, Richard

    2013-01-01

    Beginning in the spring of 2011 the Center for the Study of Curriculum at Michigan State University conducted a survey of school district curriculum directors/supervisors in the 41 states that had officially adopted the new Common Core State Standards for Mathematics (CCSSM). The Center's goal was to provide baseline information to inform and…

  3. Assessing Current State Science Teaching and Learning Standards for Ability to Achieve Climate Science Literacy

    NASA Astrophysics Data System (ADS)

    Busch, K. C.

    2012-12-01

    Even though there exists a high degree of consensus among scientists about climate change, doubt has actually increased over the last five years within the general U.S. public. In 2006, 79% of those polled agreed that there is evidence for global warming, while only 59% agreed in 2010 (Pew Research Center, 2010). The source for this doubt can be partially attributed to lack of knowledge. Formal education is one mechanism that potentially can address inadequate public understanding as school is the primary place where students - and future citizens - learn about the climate. In a joint effort, several governmental agencies, non-governmental organizations, scientists and educators have created a framework called The Essential Principles of Climate Science Literacy, detailing seven concepts that are deemed vital for individuals and communities to understand Earth's climate system (USGCRP, 2009). Can students reach climate literacy - as defined by these 7 concepts - if they are taught using a curriculum based on the current state standards? To answer this question, the K-12 state science teaching and learning standards for Texas and California - two states that heavily influence nation-wide textbook creation - were compared against the Essential Principles. The data analysis consisted of two stages, looking for: 1) direct reference to "climate" and "climate change" and 2) indirect reference to the 7 Essential Principles through axial coding. The word "climate" appears in the California K-12 science standards 4 times and in the Texas standards 7 times. The word "climate change" appears in the California and Texas standards only 3 times each. Indirect references to the 7 Essential Principles of climate science literacy were more numerous. Broadly, California covered 6 of the principles while Texas covered all 7. In looking at the 7 principles, the second one "Climate is regulated by complex interactions among component of the Earth system" was the most substantively

  4. Drafting the proteome landscape of myeloid-derived suppressor cells.

    PubMed

    Gato, María; Blanco-Luquin, Idoia; Zudaire, Maribel; de Morentin, Xabier Martínez; Perez-Valderrama, Estela; Zabaleta, Aintzane; Kochan, Grazyna; Escors, David; Fernandez-Irigoyen, Joaquín; Santamaría, Enrique

    2016-01-01

    Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of cells that are defined by their myeloid origin, immature state, and ability to potently suppress T-cell responses. They regulate immune responses and the population significantly increases in the tumor microenvironment of patients with glioma and other malignant tumors. For their study, MDSCs are usually isolated from the spleen or directly of tumors from a large number of tumor-bearing mice although promising ex vivo differentiated MDSC production systems have been recently developed. During the last years, proteomics has emerged as a powerful approach to analyze MDSCs proteomes using shotgun-based mass spectrometry (MS), providing functional information about cellular homeostasis and metabolic state at a global level. Here, we will revise recent proteome profiling studies performed in MDSCs from different origins. Moreover, we will perform an integrative functional analysis of the protein compilation derived from these large-scale proteomic studies in order to obtain a comprehensive view of MDSCs biology. Finally, we will also discuss the potential application of high-throughput proteomic approaches to study global proteome dynamics and post-translational modifications (PTMs) during the differentiation process of MDSCs that will greatly boost the identification of novel MDSC-specific therapeutic targets to apply in cancer immunotherapy. PMID:26403437

  5. Transient and steady-state dark current mechanisms in polycrystalline mercuric iodide X-ray imaging detectors

    NASA Astrophysics Data System (ADS)

    Kabir, M. Z.

    2014-02-01

    A theoretical model for describing bias-dependent time transient and steady-state dark current behaviors in polycrystalline mercuric iodide (poly-HgI2) based X-ray image detectors is developed. The model considers carrier injection from the metal electrode, bulk carrier depletion process, and bulk thermal generation current from the mid-gap states. The transient dark current is mainly determined by the initial carrier depletion process. At a very low applied field (less than 0.05 V/μm), the steady-state dark current is almost equal to the bulk thermal generation current. However, the injection current increases sharply with increasing the applied field. The steady-state dark current in poly-HgI2 detectors at normal operating field (~ 1 V/μm) is mainly controlled by the Schottky emission of electrons from the metal/HgI2 contact. The fitting of the physics-based model to the experimental results estimates the effective barrier height and interface defect states for injecting electrons from the metal to poly-HgI2 layer in various poly-HgI2 detectors.

  6. Mass Spectrometry-based Proteomics and Peptidomics for Systems Biology and Biomarker Discovery

    PubMed Central

    Cunningham, Robert; Ma, Di; Li, Lingjun

    2013-01-01

    The scientific community has shown great interest in the field of mass spectrometry-based proteomics and peptidomics for its applications in biology. Proteomics technologies have evolved to produce large datasets of proteins or peptides involved in various biological and disease progression processes producing testable hypothesis for complex biological questions. This review provides an introduction and insight to relevant topics in proteomics and peptidomics including biological material selection, sample preparation, separation techniques, peptide fragmentation, post-translation modifications, quantification, bioinformatics, and biomarker discovery and validation. In addition, current literature and remaining challenges and emerging technologies for proteomics and peptidomics are presented. PMID:24504115

  7. Proteogenomics: Integrating Next-Generation Sequencing and Mass Spectrometry to Characterize Human Proteomic Variation

    NASA Astrophysics Data System (ADS)

    Sheynkman, Gloria M.; Shortreed, Michael R.; Cesnik, Anthony J.; Smith, Lloyd M.

    2016-06-01

    Mass spectrometry–based proteomics has emerged as the leading method for detection, quantification, and characterization of proteins. Nearly all proteomic workflows rely on proteomic databases to identify peptides and proteins, but these databases typically contain a generic set of proteins that lack variations unique to a given sample, precluding their detection. Fortunately, proteogenomics enables the detection of such proteomic variations and can be defined, broadly, as the use of nucleotide sequences to generate candidate protein sequences for mass spectrometry database searching. Proteogenomics is experiencing heightened significance due to two developments: (a) advances in DNA sequencing technologies that have made complete sequencing of human genomes and transcriptomes routine, and (b) the unveiling of the tremendous complexity of the human proteome as expressed at the levels of genes, cells, tissues, individuals, and populations. We review here the field of human proteogenomics, with an emphasis on its history, current implementations, the types of proteomic variations it reveals, and several important applications.

  8. Proteogenomics: Integrating Next-Generation Sequencing and Mass Spectrometry to Characterize Human Proteomic Variation.

    PubMed

    Sheynkman, Gloria M; Shortreed, Michael R; Cesnik, Anthony J; Smith, Lloyd M

    2016-06-12

    Mass spectrometry-based proteomics has emerged as the leading method for detection, quantification, and characterization of proteins. Nearly all proteomic workflows rely on proteomic databases to identify peptides and proteins, but these databases typically contain a generic set of proteins that lack variations unique to a given sample, precluding their detection. Fortunately, proteogenomics enables the detection of such proteomic variations and can be defined, broadly, as the use of nucleotide sequences to generate candidate protein sequences for mass spectrometry database searching. Proteogenomics is experiencing heightened significance due to two developments: (a) advances in DNA sequencing technologies that have made complete sequencing of human genomes and transcriptomes routine, and (b) the unveiling of the tremendous complexity of the human proteome as expressed at the levels of genes, cells, tissues, individuals, and populations. We review here the field of human proteogenomics, with an emphasis on its history, current implementations, the types of proteomic variations it reveals, and several important applications. PMID:27049631

  9. An empirical strategy for characterizing bacterial proteomes across species in the absence of genomic sequences

    SciTech Connect

    Turse, Joshua E.; Marshall, Matthew J.; Fredrickson, Jim K.; Lipton, Mary S.; Callister, Stephen J.

    2010-11-12

    Current methods in proteomics are dependent on the availability of sequenced genomes to identify proteins. However, genomic sequences are not always available for bacteria or microbial communities, even with high throughput sequencing technology becoming more readily available. Nevertheless, the homology that exists between related bacteria makes possible the extraction of meaningful biological information from an organism’s, or community’s proteome using the genomic sequence of a near neighbor. Here, a cross-organism search strategy was used to look at the amount of proteomics information obtainable with relative genetic distance from a near neighbor organism and to identify proteins in the proteome of minimally characterized environmental isolates. We conclude that closely related organisms with sequenced genomes, can be used to characterize proteomes of organisms with unsequenced genomes. In general, a cross-organism search strategy demonstrates the first step to use of sequences genomes to evaluate the proteomes of environmental bacteria and microbial communities that have no sequenced genome

  10. Proteogenomics: Integrating Next-Generation Sequencing and Mass Spectrometry to Characterize Human Proteomic Variation

    PubMed Central

    Sheynkman, Gloria M.; Shortreed, Michael R.; Cesnik, Anthony J.; Smith, Lloyd M.

    2016-01-01

    Mass spectrometry–based proteomics has emerged as the leading method for detection, quantification, and characterization of proteins. Nearly all proteomic workflows rely on proteomic databases to identify peptides and proteins, but these databases typically contain a generic set of proteins that lack variations unique to a given sample, precluding their detection. Fortunately, proteogenomics enables the detection of such proteomic variations and can be defined, broadly, as the use of nucleotide sequences to generate candidate protein sequences for mass spectrometry database searching. Proteogenomics is experiencing heightened significance due to two developments: (a) advances in DNA sequencing technologies that have made complete sequencing of human genomes and transcriptomes routine, and (b) the unveiling of the tremendous complexity of the human proteome as expressed at the levels of genes, cells, tissues, individuals, and populations. We review here the field of human proteogenomics, with an emphasis on its history, current implementations, the types of proteomic variations it reveals, and several important applications. PMID:27049631

  11. Automated glycopeptide analysis--review of current state and future directions.

    PubMed

    Dallas, David C; Martin, William F; Hua, Serenus; German, J Bruce

    2013-05-01

    Glycosylation of proteins is involved in immune defense, cell-cell adhesion, cellular recognition and pathogen binding and is one of the most common and complex post-translational modifications. Science is still struggling to assign detailed mechanisms and functions to this form of conjugation. Even the structural analysis of glycoproteins-glycoproteomics-remains in its infancy due to the scarcity of high-throughput analytical platforms capable of determining glycopeptide composition and structure, especially platforms for complex biological mixtures. Glycopeptide composition and structure can be determined with high mass-accuracy mass spectrometry, particularly when combined with chromatographic separation, but the sheer volume of generated data necessitates computational software for interpretation. This review discusses the current state of glycopeptide assignment software-advances made to date and issues that remain to be addressed. The various software and algorithms developed so far provide important insights into glycoproteomics. However, there is currently no freely available software that can analyze spectral data in batch and unambiguously determine glycopeptide compositions for N- and O-linked glycopeptides from relevant biological sources such as human milk and serum. Few programs are capable of aiding in structural determination of the glycan component. To significantly advance the field of glycoproteomics, analytical software and algorithms are required that: (i) solve for both N- and O-linked glycopeptide compositions, structures and glycosites in biological mixtures; (ii) are high-throughput and process data in batches; (iii) can interpret mass spectral data from a variety of sources and (iv) are open source and freely available. PMID:22843980

  12. The current and projected economic burden of Parkinson's disease in the United States.

    PubMed

    Kowal, Stacey L; Dall, Timothy M; Chakrabarti, Ritashree; Storm, Michael V; Jain, Anjali

    2013-03-01

    Parkinson's disease (PD), following Alzheimer's disease, is the second-most common neurodegenerative disorder in the United States. A lack of treatment options for changing the trajectory of disease progression, in combination with an increasing elderly population, portends a rising economic burden on patients and payers. This study combined information from nationally representative surveys to create a burden of PD model. The model estimates disease prevalence, excess healthcare use and medical costs, and nonmedical costs for each demographic group defined by age and sex. Estimated prevalence rates and costs were applied to the U.S. Census Bureau's 2010 to 2050 population data to estimate current and projected burden based on changing demographics. We estimate that approximately 630,000 people in the United States had diagnosed PD in 2010, with diagnosed prevalence likely to double by 2040. The national economic burden of PD exceeds $14.4 billion in 2010 (approximately $22,800 per patient). The population with PD incurred medical expenses of approximately $14 billion in 2010, $8.1 billion higher ($12,800 per capita) than expected for a similar population without PD. Indirect costs (e.g., reduced employment) are conservatively estimated at $6.3 billion (or close to $10,000 per person with PD). The burden of chronic conditions such as PD is projected to grow substantially over the next few decades as the size of the elderly population grows. Such projections give impetus to the need for innovative new treatments to prevent, delay onset, or alleviate symptoms of PD and other similar diseases. PMID:23436720

  13. Report to Congress: Summary Report of the Assessment of Current State Practices in Title XX Funded Day Care Programs.

    ERIC Educational Resources Information Center

    Administration for Children, Youth, and Families (DHHS), Washington, DC.

    In 1980 the federal government mandated that assistance be given states to conduct systematic assessment of current practices in Title XX funded day care programs and that a summary report of this assessment be provided to Congress. Assessment findings are given in this document. Overall, provider practices exceeded state licensing standards and…

  14. High Charge State Ions Extracted from Metal Plasmas in the Transition Regime from Vacuum Spark to High Current Vacuum Arc

    SciTech Connect

    Yushkov, Georgy Yu.; Anders, A.

    2008-06-19

    Metal ions were extracted from pulsed discharge plasmas operating in the transition region between vacuum spark (transient high voltage of kV) and vacuum arc (arc voltage ~;; 20 V). At a peak current of about 4 kA, and with a pulse duration of 8 ?s, we observed mean ion charges states of about 6 for several cathode materials. In the case of platinum, the highest average charge state was 6.74 with ions of charge states as high as 10 present. For gold we found traces of charge state 11, with the highest average charge state of 7.25. At currents higher than 5 kA, non-metallic contaminations started to dominate the ion beam, preventing further enhancement of the metal charge states.

  15. Proteome Analyses of Hepatocellular Carcinoma

    PubMed Central

    Megger, Dominik A.; Naboulsi, Wael; Meyer, Helmut E.; Sitek, Barbara

    2014-01-01

    Proteomics has evolved into a powerful and widely used bioanalytical technique in the study of cancer, especially hepatocellular carcinoma (HCC). In this review, we provide an up to date overview of feasible proteome-analytical techniques for clinical questions. In addition, we present a broad summary of proteomic studies of HCC utilizing various technical approaches for the analysis of samples derived from diverse sources like HCC cell lines, animal models, human tissue and body fluids. PMID:26357614

  16. Outdoor cultivation of microalgae for carotenoid production: current state and perspectives.

    PubMed

    Del Campo, José A; García-González, Mercedes; Guerrero, Miguel G

    2007-04-01

    Microalgae are a major natural source for a vast array of valuable compounds, including a diversity of pigments, for which these photosynthetic microorganisms represent an almost exclusive biological resource. Yellow, orange, and red carotenoids have an industrial use in food products and cosmetics as vitamin supplements and health food products and as feed additives for poultry, livestock, fish, and crustaceans. The growing worldwide market value of carotenoids is projected to reach over US$1,000 million by the end of the decade. The nutraceutical boom has also integrated carotenoids mainly on the claim of their proven antioxidant properties. Recently established benefits in human health open new uses for some carotenoids, especially lutein, an effective agent for the prevention and treatment of a variety of degenerative diseases. Consumers' demand for natural products favors development of pigments from biological sources, thus increasing opportunities for microalgae. The biotechnology of microalgae has gained considerable progress and relevance in recent decades, with carotenoid production representing one of its most successful domains. In this paper, we review the most relevant features of microalgal biotechnology related to the production of different carotenoids outdoors, with a main focus on beta-carotene from Dunaliella, astaxanthin from Haematococcus, and lutein from chlorophycean strains. We compare the current state of the corresponding production technologies, based on either open-pond systems or closed photobioreactors. The potential of scientific and technological advances for improvements in yield and reduction in production costs for carotenoids from microalgae is also discussed. PMID:17277962

  17. Biomonitoring of Mycotoxins in Human Breast Milk: Current State and Future Perspectives.

    PubMed

    Warth, Benedikt; Braun, Dominik; Ezekiel, Chibundu N; Turner, Paul C; Degen, Gisela H; Marko, Doris

    2016-07-18

    Human breast milk is considered as the best and ideal form of nutrition for infants. However, food contaminants such as mycotoxins, which may be transferred from maternal blood to milk, are poorly described. Mycotoxins are a major group of natural toxins frequently detected in foods. Here, we review the current state-of-the-art in the monitoring of mycotoxins in human breast milk, i.e., knowledge on occurrence, metabolism, and analytical assays utilized for their quantification. We highlight that most of the data captured to date have not been verified with the precision now capable utilizing LC-MS/MS and LC-HRMS approaches. One concern is that some studies may overestimate individual measures, and most cannot capture the patterns and levels of mycotoxin mixtures. We propose accurate assessment as a priority, especially for aflatoxins, fumonisins, ochratoxin A, zearalenone, and deoxynivalenol as well as their major metabolites. However, also so-called emerging toxins such as citrinin, the enniatins, beauvericin, aurofusarin, or Alternaria toxins should be considered to evaluate their potential relevance. Key requirements for analytical quality assurance are identified and discussed to guide future developments in this area. Moreover, research needs including investigations of lactational transfer rates, the role of human metabolism for bioactivation or detoxification, and an evaluation of potential combinatory effects of different mycotoxins are pointed out. It is hoped that LC-MS based multianalyte methods will enable more accurate, rapid and affordable human biomonitoring approaches that support informed decisions for maternal and infant health. PMID:27300310

  18. Quantum well state induced oscillation of pure spin currents in Fe/Au/Pd(001) systems.

    PubMed

    Montoya, Eric; Heinrich, Bret; Girt, Erol

    2014-09-26

    Spin pumping at the ferromagnetic metal (Fe)/normal metal (Au) interface and the subsequent spin transport in Au/Pd heterostructures is studied using ferromagnetic resonance. The spin pumping induced damping in the Fe/Pd structure is greatly suppressed by the addition of a Au spacer layer in the structure Fe/Au/Pd. The rapid decrease in the interface damping with an increasing Au layer thickness does not correspond to an expectation based on a simple spin diffusion theory in the Au layer. It is possible to account for this behavior by introducing a partial reflection of spin current at the Au/Pd interface. Furthermore, oscillations in the amplitude of spin pumping damping are observed in the Fe/Au/Pd structure as a function of Au thickness for thicknesses less than half the electron mean free path of bulk Au. This new effect indicates a formation of quantum well states in the accumulated spin density in the Au spacer that affect the time irreversible process of spin pumping. PMID:25302912

  19. Microbiological fermentation of lignocellulosic biomass: current state and prospects of mathematical modeling.

    PubMed

    Lübken, Manfred; Gehring, Tito; Wichern, Marc

    2010-02-01

    The anaerobic fermentation process has achieved growing importance in practice in recent years. Anaerobic fermentation is especially valuable because its end product is methane, a renewable energy source. While the use of renewable energy sources has accelerated substantially in recent years, their potential has not yet been sufficiently exploited. This is especially true for biogas technology. Biogas is created in a multistage process in which different microorganisms use the energy stored in carbohydrates, fats, and proteins for their metabolism. In order to produce biogas, any organic substrate that is microbiologically accessible can be used. The microbiological process in itself is extremely complex and still requires substantial research in order to be fully understood. Technical facilities for the production of biogas are thus generally scaled in a purely empirical manner. The efficiency of the process, therefore, corresponds to the optimum only in the rarest cases. An optimal production of biogas, as well as a stable plant operation requires detailed knowledge of the biochemical processes in the fermenter. The use of mathematical models can help to achieve the necessary deeper understanding of the process. This paper reviews both the history of model development and current state of the art in modeling anaerobic digestion processes. PMID:19960191

  20. Cancer Treatment–Related Cardiotoxicity: Current State of Knowledge and Future Research Priorities

    PubMed Central

    Adhikari, Bishow; Brell, Joanna; Davis, Myrtle; Desvigne-Nickens, Patrice; Freedman, Andrew; Minasian, Lori; Force, Thomas; Remick, Scot C.

    2014-01-01

    Cardiotoxicity resulting from direct myocyte damage has been a known complication of cancer treatment for decades. More recently, the emergence of hypertension as a clinically significant side effect of several new agents has been recognized as adversely affecting cancer treatment outcomes. With cancer patients living longer, in part because of treatment advances, these adverse events have become increasingly important to address. However, little is known about the cardiovascular pathogenic mechanisms associated with cancer treatment and even less about how to optimally prevent and manage short- and long-term cardiovascular complications, leading to improved patient safety and clinical outcomes. To identify research priorities, allocate resources, and establish infrastructure required to address cardiotoxicity associated with cancer treatment, the National Cancer Institute (NCI) and National Heart, Lung and Blood Institute (NHLBI) sponsored a two-day workshop, “Cancer treatment–related cardiotoxicity: Understanding the current state of knowledge and future research priorities,” in March 2013 in Bethesda, MD. Participants included leading oncology and cardiology researchers and health professionals, patient advocates and industry representatives, with expertise ranging from basic to clinical science. Attendees were charged with identifying research opportunities to advance the understanding of cancer treatment–related cardiotoxicity across basic and clinical science. This commentary highlights the key discussion points and overarching recommendations from that workshop. PMID:25210198

  1. Hispanic Older Adult Health & Longevity in the United States: Current Patterns & Concerns for the Future

    PubMed Central

    Hummer, Robert A.; Hayward, Mark D.

    2015-01-01

    The Hispanic population aged sixty-five and over – the most socioeconomically disadvantaged subset of America’s elderly – is projected to quintuple between 2012 and 2050. While current longevity patterns for Hispanics relative to whites are favorable, old-age functioning and disability patterns for Hispanics are unfavorable and have serious implications for caregivers; families; and local, state, and federal governments. Troubling signs for the future Hispanic population (which are shared to varying degrees with other vulnerable groups) include the unresolved legal status of unauthorized immigrants, continued low levels of insurance coverage even after health care reform, some unfavorable trends in health behaviors, and continued disadvantages in educational attainment and income relative to whites. We urge policy-makers to deal with these potentially problematic health and well-being issues. Not doing so could have detrimental consequences for the future of the Hispanic population as well as other at-risk groups and, by extension, the U.S. elderly population as a whole. PMID:26082561

  2. Preserving Astronomy's Photographic Legacy: Current State and the Future of North American Astronomical Plates

    NASA Astrophysics Data System (ADS)

    Osborn, W.; Robbins, L.

    2009-08-01

    This book contains articles on preserving astronomy's valuable heritage of photographic observations, most of which are on glass plates. It is intended to serve as a reference for institutions charged with preserving and managing plate archives and astronomers interested in using archival photographic plates in their research. The first portion of the book focuses on previous activities and recommendations related to plate archiving. These include actions taken by the International Astronomical Union, activities in Europe and a detailed account of a workshop on preserving astronomical photographic data held in 2007 at the Pisgah Astronomical Research Institute, North Carolina. The workshop discussions covered a wide range of issues that must be considered in any effort to archive plates and culminated in a set of recommendations on preserving, cataloging and making publicly available these irreplaceable data. The second part of the book reports on some recent efforts to implement the recommendations. These include essays on the recently established Astronomical Photographic Data Archive, projects to make photographic collections available electronically, evaluations of commercial scanners for digitization of astronomical plates and the case for the continuing value of these data along with a report on the census of astronomical plate collections in North America carried out in 2008. The census cataloged the locations, numbers, and types of astronomical plates in the US and Canada. Comprehensive appendices identify all the significant collections in North America and detail the current contents, state and status of their holdings.

  3. Pediatric obesity pharmacotherapy: current state of the field, review of the literature and clinical trial considerations.

    PubMed

    Kelly, A S; Fox, C K; Rudser, K D; Gross, A C; Ryder, J R

    2016-07-01

    Despite the increasing number of medications recently approved to treat obesity among adults, few agents have been formally evaluated in children or adolescents for this indication. Moreover, there is a paucity of guidance in the literature addressing best practices with regard to pediatric obesity pharmacotherapy clinical trial design, and only general recommendations have been offered by regulatory agencies on this topic. The purposes of this article are to (1) offer a background of the current state of the field of pediatric obesity medicine, (2) provide a brief review of the literature summarizing pediatric obesity pharmacotherapy clinical trials, and (3) highlight and discuss some of the unique aspects that should be considered when designing and conducting high-quality clinical trials evaluating the safety and efficacy of obesity medications in children and adolescents. Suggestions are offered in the areas of target population and eligibility criteria, clinical trial end-point selection, trial duration, implementation of lifestyle modification therapy and recruitment and retention of participants. Efforts should be made to design and conduct trials appropriately to ensure that high-quality evidence is generated on the safety and efficacy of various medications used to treat pediatric obesity. PMID:27113643

  4. Advances in hepatitis C therapy: What is the current state - what come’s next?

    PubMed Central

    Zopf, Steffen; Kremer, Andreas E; Neurath, Markus F; Siebler, Juergen

    2016-01-01

    Chronic hepatitis C virus (HCV) infection affects 80-160 million people worldwide and is one of the leading causes of chronic liver disease. It is only a few years ago that standard treatment regimes were based on pegylated interferon alpha and ribavirin. However, treatment of HCV has undergone a revolutionary change in recent years. The admission of the nucleotide polymerase inhibitor Sofosbuvir enabled an interferon-free regimen with direct antiviral agents (DAA). Meanwhile seven DAAs are available and can be applied in several combinations for 8 to 24 wk depending on HCV genotype and patient characteristics such as cirrhosis and chronic renal failure. High rates of sustained virological response (SVR) rates can be achieved with these novel drugs. Even in difficult to treat populations such as patients with liver cirrhosis, HCV-human immunodeficiency virus co-infections, after liver transplantion, or with chronic kidney disease comparable high rates of SVR can be achieved. The anticipated 2nd generation DAAs are strikingly effective in patients so far classified as difficult to treat including decompensated liver cirrhosis or post-transplant patients. These 2nd generations DAAs will have higher resistance barriers, higher antiviral effects and a pan-genotypic spectrum. This review highlights the current state of the art of antiviral treatment in hepatitis C and gives an outlook for upcoming therapies. PMID:26839638

  5. Floodflow characteristics of Current River at Arkansas state highway 328 near Reyno, Arkansas

    USGS Publications Warehouse

    Gilstrap, R.C.; Neely, Braxtel L., Jr.

    1986-01-01

    Arkansas State Highway 328 in Randolph County crosses Current River about 1.5 mi northwest of Reyno, Arkansas. A main channel bridge with a relief bridge on each side, five culverts, and a bridge on the west side of the valley were the existing flow structures prior to a December 1982 flood. After the December 1982 flood, 34 additional culverts were installed along the highway. The flood of December 3, 1982, which had a computed peak discharge of 85,300 cu ft/sec and a recurrence interval of about 8 years, caused considerable damage to the highway being reconstructed. The flood of April 1985, which had a discharge of 48,000 cu ft/sec and a recurrence interval of about 2 years, also caused damage to fill areas of the reconstructed highway. A hydraulic analysis was conducted for the 5-, 10-, 25-, 50- and 100-year flood and the floods of December 1982 and April 1985 to determine the river stages before and after Highway 328 was reconstructed. Results of the study indicate that the water surface along the upstream water surface elevations less than 0.1 ft. (USGS)

  6. Carbon sequestration by forests of the United States. Current status and projections to the year 2040

    NASA Astrophysics Data System (ADS)

    Turner, David P.; Koerper, Greg J.; Harmon, Mark E.; Lee, Jeffrey J.

    1995-02-01

    National-level forest carbon budgets are of interest in relation to understanding the global carbon cycle, comparing anthropogenic and biogenic sources of carbon, and developing possible strategies for conserving and sequestering carbon. In this study, forest carbon pools and flux for timberlands in the conterminous United States were projected over the coming 50years by coupling a forest economics model, a forest inventory model and a forest carbon model. In the base case scenario, US forests sequestered carbon in the 1990s at a rate of 80 Tg yr-1 but came close to carbon equilibrium by the 2020s. The dominant factors driving this change were an increasing forest harvest, a decreasing forest land base, and a reduction in average stand age. Scenarios in which alternative forest policy options were implemented related to increased paper recycling and increased afforestation (5×106 ha) produced long-term increases in carbon sequestration on the forest land base of up to 15 Tg yr-1. The carbon sink on the forest land base currently offsets 6% of US fossil carbon emissions but that proportion is likely to decrease over the coming decades.

  7. Current state and future direction of computer systems at NASA Langley Research Center

    NASA Technical Reports Server (NTRS)

    Rogers, James L. (Editor); Tucker, Jerry H. (Editor)

    1992-01-01

    Computer systems have advanced at a rate unmatched by any other area of technology. As performance has dramatically increased there has been an equally dramatic reduction in cost. This constant cost performance improvement has precipitated the pervasiveness of computer systems into virtually all areas of technology. This improvement is due primarily to advances in microelectronics. Most people are now convinced that the new generation of supercomputers will be built using a large number (possibly thousands) of high performance microprocessors. Although the spectacular improvements in computer systems have come about because of these hardware advances, there has also been a steady improvement in software techniques. In an effort to understand how these hardware and software advances will effect research at NASA LaRC, the Computer Systems Technical Committee drafted this white paper to examine the current state and possible future directions of computer systems at the Center. This paper discusses selected important areas of computer systems including real-time systems, embedded systems, high performance computing, distributed computing networks, data acquisition systems, artificial intelligence, and visualization.

  8. Primaquine pharmacology in the context of CYP 2D6 pharmacogenomics: Current state of the art.

    PubMed

    Marcsisin, Sean R; Reichard, Gregory; Pybus, Brandon S

    2016-05-01

    Primaquine is the only antimalarial drug available to clinicians for the treatment of relapsing forms of malaria. Primaquine development and usage dates back to the 1940s and has been administered to millions of individuals to treat and eliminate malaria infections. Primaquine therapy is not without disadvantages, however, as it can cause life threatening hemolysis in humans with glucose-6-phosphate dehydrogenase (G6PD) deficiency. In addition, the efficacy of primaquine against relapsing malaria was recently linked to CYP 2D6 mediated activation to an active metabolite, the structure of which has escaped definitive identification for over 75years. CYP 2D6 is highly polymorphic among various human populations adding further complexity to a comprehensive understanding of primaquine pharmacology. This review aims to discuss primaquine pharmacology in the context of state of the art understanding of CYP 2D6 mediated 8-aminoquinoline metabolic activation, and shed light on the current knowledge gaps of 8-aminoquinoline mechanistic understanding against relapsing malaria. PMID:27016470

  9. Advances in hepatitis C therapy: What is the current state - what come's next?

    PubMed

    Zopf, Steffen; Kremer, Andreas E; Neurath, Markus F; Siebler, Juergen

    2016-01-28

    Chronic hepatitis C virus (HCV) infection affects 80-160 million people worldwide and is one of the leading causes of chronic liver disease. It is only a few years ago that standard treatment regimes were based on pegylated interferon alpha and ribavirin. However, treatment of HCV has undergone a revolutionary change in recent years. The admission of the nucleotide polymerase inhibitor Sofosbuvir enabled an interferon-free regimen with direct antiviral agents (DAA). Meanwhile seven DAAs are available and can be applied in several combinations for 8 to 24 wk depending on HCV genotype and patient characteristics such as cirrhosis and chronic renal failure. High rates of sustained virological response (SVR) rates can be achieved with these novel drugs. Even in difficult to treat populations such as patients with liver cirrhosis, HCV-human immunodeficiency virus co-infections, after liver transplantion, or with chronic kidney disease comparable high rates of SVR can be achieved. The anticipated 2(nd) generation DAAs are strikingly effective in patients so far classified as difficult to treat including decompensated liver cirrhosis or post-transplant patients. These 2(nd) generations DAAs will have higher resistance barriers, higher antiviral effects and a pan-genotypic spectrum. This review highlights the current state of the art of antiviral treatment in hepatitis C and gives an outlook for upcoming therapies. PMID:26839638

  10. The Current Status and Future Direction of High Magnetic Field Science in the United States

    SciTech Connect

    Lancaster, James

    2013-11-01

    This grant provided partial support for the National Research Council (NRC) study that assesses the current status of high magnetic field research in the United States and provides recommendations to guide the future of research and technology development for this area given the needs of user communities and in the context of other programs worldwide.. A pdf version of the report is available for download, for free, at http://www.nap.edu/catalog.php?record_id=18355. The science drivers fall into 4 broad areas—(1) condensed matter and materials physics; (2) chemistry, biochemistry, and biology; (3) medical and life science studies; and (4) other fields such as high-energy physics, plasma physics, and particle astrophysics. Among the topics covered in the report’s findings, conclusions, and recommendations are a recognition that there is a continuing need for a centralized facility but also that clear benefits will flow to research communities from decentralized facilities. According to the report, support agencies should evaluate whether to establish such facilities when 32 Tesla superconducting magnets become available. The report also recommends the provision of facilities that combine magnetic fields with scattering facilities and THz radiation sources, and sets out specific magnet goals for magnets needed in several areas of research.

  11. Proteomic and Microscopic Strategies towards the Analysis of the Cytoskeletal Networks in Major Neuropsychiatric Disorders

    PubMed Central

    Coumans, Joëlle V. F.; Palanisamy, Suresh K. A.; McFarlane, Jim; Moens, Pierre D. J.

    2016-01-01

    Mental health disorders have become worldwide health priorities. It is estimated that in the next 20 years they will account for a 16 trillion United State dollars (US$) loss. Up to now, the underlying pathophysiology of psychiatric disorders remains elusive. Altered cytoskeleton proteins expression that may influence the assembly, organization and maintenance of cytoskeletal integrity has been reported in major depressive disorders, schizophrenia and to some extent bipolar disorders. The use of quantitative proteomics, dynamic microscopy and super-resolution microscopy to investigate disease-specific protein signatures holds great promise to improve our understanding of these disorders. In this review, we present the currently available quantitative proteomic approaches use in neurology, gel-based, stable isotope-labelling and label-free methodologies and evaluate their strengths and limitations. We also reported on enrichment/subfractionation methods that target the cytoskeleton associated proteins and discuss the need of alternative methods for further characterization of the neurocytoskeletal proteome. Finally, we present live cell imaging approaches and emerging dynamic microscopy technology that will provide the tools necessary to investigate protein interactions and their dynamics in the whole cells. While these areas of research are still in their infancy, they offer huge potential towards the understanding of the neuronal network stability and its modification across neuropsychiatric disorders. PMID:27104521

  12. Dynamic proteome analysis of Cyanothece sp. ATCC 51142 under constant light

    SciTech Connect

    Aryal, Uma K.; Stockel, Jana; Welsh, Eric A.; Gritsenko, Marina A.; Nicora, Carrie D.; Koppenaal, David W.; Smith, Richard D.; Pakrasi, Himadri B.; Jacobs, Jon M.

    2012-02-03

    Understanding the dynamic nature of protein abundances provides insights into protein turnover not readily apparent from conventional, static mass spectrometry measurements. This level of data is particularly informative when surveying protein abundances in biological systems subjected to large perturbations or alterations in environment such as cyanobacteria. Our current analysis expands upon conventional proteomic approaches in cyanobacteria by measuring dynamic changes of the proteome using a 13C15N-L-leucine metabolic labeling in Cyanothece ATCC51142. Metabolically labeled Cyanothece ATCC51142 cells grown under nitrogen sufficient conditions in continuous light were monitored longitudinally for isotope incorporation over a 48 h period, revealing 422 proteins with dynamic changes in abundances. In particular, proteins involved in carbon fixation, pentose phosphate pathway, cellular protection, redox regulation, protein folding, assembly and degradation showed higher levels of isotope incorporation suggesting that these biochemical pathways are important for growth under non-diazotrophic conditions. Calculation of relative isotope abundances (RIA) values allowed to measure actual active protein synthesis over time for different biochemical pathways under non-diazotrophic conditions. Overall results demonstrated the utility of 'non-steady state' pulsed metabolic labeling for systems-wide dynamic quantification of the proteome in Cyanothece ATCC51142 that can also be applied to other cyanobacteria.

  13. Computational and experimental approaches to chart the Escherichia coli cell-envelope-associated proteome and interactome.

    PubMed

    Díaz-Mejía, Juan Javier; Babu, Mohan; Emili, Andrew

    2009-01-01

    The bacterial cell-envelope consists of a complex arrangement of lipids, proteins and carbohydrates that serves as the interface between a microorganism and its environment or, with pathogens, a human host. Escherichia coli has long been investigated as a leading model system to elucidate the fundamental mechanisms underlying microbial cell-envelope biology. This includes extensive descriptions of the molecular identities, biochemical activities and evolutionary trajectories of integral transmembrane proteins, many of which play critical roles in infectious disease and antibiotic resistance. Strikingly, however, only half of the c. 1200 putative cell-envelope-related proteins of E. coli currently have experimentally attributed functions, indicating an opportunity for discovery. In this review, we summarize the state of the art of computational and proteomic approaches for determining the components of the E. coli cell-envelope proteome, as well as exploring the physical and functional interactions that underlie its biogenesis and functionality. We also provide a comprehensive comparative benchmarking analysis on the performance of different bioinformatic and proteomic methods commonly used to determine the subcellular localization of bacterial proteins. PMID:19054114

  14. Computational and experimental approaches to chart the Escherichia coli cell-envelope-associated proteome and interactome

    PubMed Central

    Díaz-Mejía, Juan Javier; Babu, Mohan; Emili, Andrew

    2009-01-01

    The bacterial cell-envelope consists of a complex arrangement of lipids, proteins and carbohydrates that serves as the interface between a microorganism and its environment or, with pathogens, a human host. Escherichia coli has long been investigated as a leading model system to elucidate the fundamental mechanisms underlying microbial cell-envelope biology. This includes extensive descriptions of the molecular identities, biochemical activities and evolutionary trajectories of integral transmembrane proteins, many of which play critical roles in infectious disease and antibiotic resistance. Strikingly, however, only half of the c. 1200 putative cell-envelope-related proteins of E. coli currently have experimentally attributed functions, indicating an opportunity for discovery. In this review, we summarize the state of the art of computational and proteomic approaches for determining the components of the E. coli cell-envelope proteome, as well as exploring the physical and functional interactions that underlie its biogenesis and functionality. We also provide a comprehensive comparative benchmarking analysis on the performance of different bioinformatic and proteomic methods commonly used to determine the subcellular localization of bacterial proteins. PMID:19054114

  15. Current state and prospects of carbon management in high latitudes of Northern Eurasia

    NASA Astrophysics Data System (ADS)

    Schepaschenko, Dmitry; Shvidenko, Anatoly

    2010-05-01

    The current state and trajectories of future development of natural landscapes in high latitudes of Northern Eurasia are defined inter alia by (1) current unsatisfactory social and economic situation in boreal Northern Eurasia; (2) the dramatic magnitude of on-going and expected climatic change (warming up to 10-12oC under global warming at 4oC); (3) increasing anthropogenic pressure, particularly in regions of intensive oil and gas exploration and extraction; (4) large areas of sparsely populated and practically unmanaged land; (5) vulnerability of northern ecosystems which historically developed under cold climates and buffering capacity of which is not well known; (6) risk of catastrophic natural disturbances (fire, insect outbreaks) whose frequency and severity have accelerated during recent decades; and (7) high probability of irreversible changes of vegetation cover. These specifics are overlapped with insufficient governance of natural renewable resources (e.g., forests) and destructed practice of industrial development of new territories (oil and gas extraction and exploration, metallurgy etc.). Based on a full carbon account for terrestrial vegetation ecosystems of Northern Eurasia, we analyze the relative impacts of major drivers on magnitude and uncertainty of the Net Ecosystem Carbon Balance (NECB) under current and expected climate and environment. Dynamic trends and interannual variability of NECB are mostly dependent on weather conditions during growth seasons of individual years, regimes of natural disturbances, and anthropogenic impacts on ecosystems. In a short term, disturbances and human impacts cause a theoretically 'manageable' part of the full carbon account, which on average is estimated to be of about 20% of annual net primary production. In a long term, thawing of permafrost and change of hydrological regimes of vast territories may result in a catastrophic decline of the forested area and wide distribution of 'green desertification'. The

  16. Characterizing the Dynamics of Proteasome Complexes by Proteomics Approaches

    PubMed Central

    Kaake, Robyn M.; Kao, Athit; Yu, Clinton

    2014-01-01

    Abstract Significance: The proteasome is the degradation machine of the ubiquitin-proteasome system, which is critical in controlling many essential biological processes. Aberrant regulation of proteasome-dependent protein degradation can lead to various human diseases, and general proteasome inhibitors have shown efficacy for cancer treatments. Though clinically effective, current proteasome inhibitors have detrimental side effects and, thus, better therapeutic strategies targeting proteasomes are needed. Therefore, a comprehensive characterization of proteasome complexes will provide the molecular details that are essential for developing new and improved drugs. Recent Advances: New mass spectrometry (MS)-based proteomics approaches have been developed to study protein interaction networks and structural topologies of proteasome complexes. The results have helped define the dynamic proteomes of proteasome complexes, thus providing new insights into the mechanisms underlying proteasome function and regulation. Critical Issues: The proteasome exists as heterogeneous populations in tissues/cells, and its proteome is highly dynamic and complex. In addition, proteasome complexes are regulated by various mechanisms under different physiological conditions. Consequently, complete proteomic profiling of proteasome complexes remains a major challenge for the field. Future Directions: We expect that proteomic methodologies enabling full characterization of proteasome complexes will continue to evolve. Further advances in MS instrumentation and protein separation techniques will be needed to facilitate the detailed proteomic analysis of low-abundance components and subpopulations of proteasome complexes. The results will help us understand proteasome biology as well as provide new therapeutic targets for disease diagnostics and treatment. Antioxid. Redox Signal. 21, 2444–2456. PMID:24423446

  17. Quantitative proteomic survey of endoplasmic reticulum in mouse liver.

    PubMed

    Song, Yanping; Jiang, Ying; Ying, Wantao; Gong, Yan; Yan, Yujuan; Yang, Dong; Ma, Jie; Xue, Xiaofang; Zhong, Fan; Wu, Songfeng; Hao, Yunwei; Sun, Aihua; Li, Tao; Sun, Wei; Wei, Handong; Zhu, Yunping; Qian, Xiaohong; He, Fuchu

    2010-03-01

    To gain a better understanding of the critical function of the endoplasmic reticulum (ER) in liver, we carried out a proteomic survey of mouse liver ER. The ER proteome was profiled with a new three-dimensional, gel-based strategy. From 6152 and 6935 MS spectra, 903 and 1042 proteins were identified with at least two peptides matches at 95% confidence in the rough (r) and smooth (s) ER, respectively. Comparison of the rER and sER proteomes showed that calcium-binding proteins are significantly enriched in the sER suggesting that the ion-binding function of the ER is compartmentalized. Comparison of the rat and mouse ER proteomes showed that 662 proteins were common to both, comprising 53.5% and 49.3% of those proteomes, respectively. We proposed that these proteins were stably expressed proteins that were essential for the maintenance of ER function. GO annotation with a hypergeometric model proved this hypothesis. Unexpectedly, 210 unknown proteins and some proteins previously reported to occur in the cytosol were highly enriched in the ER. This study provides a reference map for the ER proteome of liver. Identification of new ER proteins will enhance our current understanding of the ER and also suggest new functions for this organelle. PMID:20073521

  18. Proteomics in bone research.

    PubMed

    Zhang, Hengwei; Recker, Robert; Lee, Wai-Nang Paul; Xiao, Gary Guishan

    2010-02-01

    Osteoporosis is prevalent among the elderly and is a major cause of bone fracture in this population. Bone integrity is maintained by the dynamic processes of bone resorption and bone formation (bone remodeling). Osteoporosis results when there is an imbalance of the two counteracting processes. Bone mineral density, measured by dual-energy x-ray absorptiometry has been the primary method to assess fracture risk for decades. Recent studies demonstrated that measurement of bone turnover markers allows for a dynamic assessment of bone remodeling, while imaging techniques, such as dual-energy x-ray absorptiometry, do not. The application of proteomics has permitted discoveries of new, sensitive, bone turnover markers, which provide unique information for clinical diagnosis and treatment of patients with bone diseases. This review summarizes the recent findings of proteomic studies on bone diseases, properties of mesenchymal stem cells with high expansion rates and osteoblast and osteoclast differentiation, with emphasis on the role of quantitative proteomics in the study of signaling dynamics, biomarkers and discovery of therapeutic targets. PMID:20121480

  19. The proteome of schizophrenia

    PubMed Central

    Nascimento, Juliana M; Martins-de-Souza, Daniel

    2015-01-01

    On observing schizophrenia from a clinical point of view up to its molecular basis, one may conclude that this is likely to be one of the most complex human disorders to be characterized in all aspects. Such complexity is the reflex of an intricate combination of genetic and environmental components that influence brain functions since pre-natal neurodevelopment, passing by brain maturation, up to the onset of disease and disease establishment. The perfect function of tissues, organs, systems, and finally the organism depends heavily on the proper functioning of cells. Several lines of evidence, including genetics, genomics, transcriptomics, neuropathology, and pharmacology, have supported the idea that dysfunctional cells are causative to schizophrenia. Together with the above-mentioned techniques, proteomics have been contributing to understanding the biochemical basis of schizophrenia at the cellular and tissue level through the identification of differentially expressed proteins and consequently their biochemical pathways, mostly in the brain tissue but also in other cells. In addition, mass spectrometry-based proteomics have identified and precisely quantified proteins that may serve as biomarker candidates to prognosis, diagnosis, and medication monitoring in peripheral tissue. Here, we review all data produced by proteomic investigation in the last 5 years using tissue and/or cells from schizophrenic patients, focusing on postmortem brain tissue and peripheral blood serum and plasma. This information has provided integrated pictures of the biochemical systems involved in the pathobiology, and has suggested potential biomarkers, and warrant potential targets to alternative treatment therapies to schizophrenia. PMID:27336025

  20. Quantitative proteomics in Giardia duodenalis-Achievements and challenges.

    PubMed

    Emery, Samantha J; Lacey, Ernest; Haynes, Paul A

    2016-08-01

    Giardia duodenalis (syn. G. lamblia and G. intestinalis) is a protozoan parasite of vertebrates and a major contributor to the global burden of diarrheal diseases and gastroenteritis. The publication of multiple genome sequences in the G. duodenalis species complex has provided important insights into parasite biology, and made post-genomic technologies, including proteomics, significantly more accessible. The aims of proteomics are to identify and quantify proteins present in a cell, and assign functions to them within the context of dynamic biological systems. In Giardia, proteomics in the post-genomic era has transitioned from reliance on gel-based systems to utilisation of a diverse array of techniques based on bottom-up LC-MS/MS technologies. Together, these have generated crucial foundations for subcellular proteomes, elucidated intra- and inter-assemblage isolate variation, and identified pathways and markers in differentiation, host-parasite interactions and drug resistance. However, in Giardia, proteomics remains an emerging field, with considerable shortcomings evident from the published research. These include a bias towards assemblage A, a lack of emphasis on quantitative analytical techniques, and limited information on post-translational protein modifications. Additionally, there are multiple areas of research for which proteomic data is not available to add value to published transcriptomic data. The challenge of amalgamating data in the systems biology paradigm necessitates the further generation of large, high-quality quantitative datasets to accurately model parasite biology. This review surveys the current proteomic research available for Giardia and evaluates their technical and quantitative approaches, while contextualising their biological insights into parasite pathology, isolate variation and eukaryotic evolution. Finally, we propose areas of priority for the generation of future proteomic data to explore fundamental questions in Giardia

  1. Overview of current marine juvenile salmon research by the United States

    USGS Publications Warehouse

    Helle, John H.; Eisner, L.B.; Farley, Edward V., Jr.; Martinson, Ellen C.; Martinson, Angela; Moss, Jamal H.; Murphy, James M.; Orsi, Joseph A.; Sturdevant, Mollly V.; Wertheimer, Alex C.; Wing, Bruce L.; Brodeur, R.D.; Emmett, Robert; Bucher, Cynthia; MacFarlane, Bruce; Harding, Jeff; Ammann, Arnold; Zimmerman, Christian E.

    2007-01-01

    A history of juvenile salmon research on Pacific salmon in coastal areas conducted by the United States (U.S.) was published by Brodeur et al. (2003). Presently, juvenile Pacific salmon research in the U.S. occurs in the coastal areas of all of the Pacific states: California, Oregon, Washington, and Alaska (Fig. 1). Major objectives of this research are to understand how dynamics in marine ecosystems influence migration, distribution, growth, and survival of juvenile salmon during their early ocean residence. Several large-scale studies in coastal areas from California to Alaska are currently being conducted by the National Oceanic and Atmospheric Administration (NOAA), National Marine Fisheries Service (NMFS), in collaboration with university and state scientists. Studies off California are operated by the Southwest Fisheries Science Center, Santa Cruz Laboratory in Santa Cruz, California and University of California Santa Cruz. Studies off Oregon and Washington are operated by the Northwest Fisheries Science Center, Newport Laboratory and Oregon State University in Newport, Oregon. Studies in the Gulf of Alaska, Bering Sea and in the seaward migration corridors in the coastal waters of southeastern Alaska are operated by the Alaska Fisheries Science Center, Auke Bay Laboratory in Juneau, Alaska, in collaboration with Alaska Department of Fish and Game, University of Alaska Fairbanks, Bering Sea Fishermen’s Association, and Yukon River Drainage Fishermen’s Association. In addition to these large studies, smaller estuarine studies on juvenile salmon occur in northwestern Alaska in Kuskokwim Bay by the U.S. Geological Survey (Anchorage) and University of Alaska Fairbanks (Juneau), and, in Norton Sound by LGL Alaska Research Associates and Norton Sound Economic Development Corporation both headquartered in Anchorage (Fig. 1). The estuarine studies on juvenile salmon in Alaska operate in shallow water and a variety of gear is used to capture salmon. A small trawl

  2. Proteomic Definitions of Mesenchymal Stem Cells

    PubMed Central

    Maurer, Martin H.

    2011-01-01

    Mesenchymal stem cells (MSCs) are pluripotent cells isolated from the bone marrow and various other organs. They are able to proliferate and self-renew, as well as to give rise to progeny of at least the osteogenic, chondrogenic, and adipogenic lineages. Despite this functional definition, MSCs can also be defined by their expression of a distinct set of cell surface markers. In the current paper, studies investigating the proteome of human MSCs are reviewed with the aim to identify common protein markers of MSCs. The proteomic analysis of MSCs revealed a distinct set of proteins representing the basic molecular inventory, including proteins for (i) cell surface markers, (ii) the responsiveness to growth factors, (iii) the reuse of developmental signaling cascades in adult stem cells, (iv) the interaction with molecules of the extracellular matrix, (v) the expression of genes regulating transcription and translation, (vi) the control of the cell number, and (vii) the protection against cellular stress. PMID:21437194

  3. Leveraging Genomics Software to Improve Proteomics Results

    SciTech Connect

    Fodor, I K; Nelson, D O

    2005-09-06

    Rigorous data analysis techniques are essential in quantifying the differential expression of proteins in biological samples of interest. Statistical methods from the microarray literature were applied to the analysis of two-dimensional difference gel electrophoresis (2-D DIGE) proteomics experiments, in the context of technical variability studies involving human plasma. Protein expression measurements were corrected to account for observed intensity-dependent biases within gels, and normalized to mitigate observed gel to gel variations. The methods improved upon the results achieved using the best currently available 2-D DIGE proteomics software. The spot-wise protein variance was reduced by 10% and the number of apparently differentially expressed proteins was reduced by over 50%.

  4. Mass spectrometry-based proteomics: existing capabilities and future directions

    SciTech Connect

    Angel, Thomas E.; Aryal, Uma K.; Hengel, Shawna M.; Baker, Erin Shammel; Kelly, Ryan T.; Robinson, Errol W.; Smith, Richard D.

    2012-05-21

    Mass spectrometry-based proteomics provides a means for identification, characterization, and quantification of biomolecules that are integral components of the processes essential for life. Characterization of proteins present in a biological system at the proteome and sub-proteomes (e.g., the phosphoproteome, proteoglycome, or degradome/peptidome) levels provides a foundation for understanding fundamental aspects as well as potentially a range of translational applications. Emerging technologies such as ion mobility separations coupled with mass spectrometry and microchip-based - proteome measurements combined with continued enhancement of MS instrumentation and separation techniques, such as reversed phase liquid chromatography and potentially capillary electrophoresis, show great promise for both broad undirected as well as targeted measurements and will be critical for e.g., the proteome-wide characterization of post translational modifications and identification, or the verification, and validation of potential biomarkers of disease. MS-based proteomics is also increasingly demonstrating great potential for contributing to our understanding of the dynamics, reactions, and roles proteins and peptides play advancing our understanding of biology on a system wide level for a wide range of applications, from investigations of microbial communities, bioremediation, and human health and disease states alike.

  5. Significance of urinary proteome pattern in renal allograft recipients.

    PubMed

    Suhail, Sufi M

    2014-01-01

    Urinary proteomics is developing as a platform of urinary biomarkers of immense potential in recent years. The definition of urinary proteome in the context of renal allograft and characterization of different proteome patterns in various graft dysfunctions have led to the development of a distinct science of this noninvasive tool. Substantial numbers of studies have shown that different renal allograft disease states, both acute and chronic, could portray unique urinary proteome pattern enabling early diagnosis of graft dysfunction and proper manipulation of immunosuppressive strategy that could impact graft prognosis. The methodology of the urinary proteome is nonetheless not more complex than that of other sophisticated assays of conventional urinary protein analysis. Moreover, the need for a centralized database is also felt by the researchers as more and more studies have been presenting their results from different corners and as systems of organizing these newly emerging data being developed at international and national levels. In this context concept of urinary proteomics in renal allograft recipients would be of significant importance in clinical transplantation. PMID:24757556

  6. Significance of Urinary Proteome Pattern in Renal Allograft Recipients

    PubMed Central

    Suhail, Sufi M.

    2014-01-01

    Urinary proteomics is developing as a platform of urinary biomarkers of immense potential in recent years. The definition of urinary proteome in the context of renal allograft and characterization of different proteome patterns in various graft dysfunctions have led to the development of a distinct science of this noninvasive tool. Substantial numbers of studies have shown that different renal allograft disease states, both acute and chronic, could portray unique urinary proteome pattern enabling early diagnosis of graft dysfunction and proper manipulation of immunosuppressive strategy that could impact graft prognosis. The methodology of the urinary proteome is nonetheless not more complex than that of other sophisticated assays of conventional urinary protein analysis. Moreover, the need for a centralized database is also felt by the researchers as more and more studies have been presenting their results from different corners and as systems of organizing these newly emerging data being developed at international and national levels. In this context concept of urinary proteomics in renal allograft recipients would be of significant importance in clinical transplantation. PMID:24757556

  7. Plasma Proteome Profiling to Assess Human Health and Disease.

    PubMed

    Geyer, Philipp E; Kulak, Nils A; Pichler, Garwin; Holdt, Lesca M; Teupser, Daniel; Mann, Matthias

    2016-03-23

    Proteins in the circulatory system mirror an individual's physiology. In daily clinical practice, protein levels are generally determined using single-protein immunoassays. High-throughput, quantitative analysis using mass-spectrometry-based proteomics of blood, plasma, and serum would be advantageous but is challenging because of the high dynamic range of protein abundances. Here, we introduce a rapid and robust "plasma proteome profiling" pipeline. This single-run shotgun proteomic workflow does not require protein depletion and enables quantitative analysis of hundreds of plasma proteomes from 1 μl single finger pricks with 20 min gradients. The apolipoprotein family, inflammatory markers such as C-reactive protein, gender-related proteins, and >40 FDA-approved biomarkers are reproducibly quantified (CV <20% with label-free quantification). Furthermore, we functionally interpret a 1,000-protein, quantitative plasma proteome obtained by simple peptide pre-fractionation. Plasma proteome profiling delivers an informative portrait of a person's health state, and we envision its large-scale use in biomedicine. PMID:27135364

  8. A synthesis of current knowledge on forests and carbon storage in the United States.

    PubMed

    McKinley, Duncan C; Ryan, Michael G; Birdsey, Richard A; Giardina, Christian P; Harmon, Mark E; Heath, Linda S; Houghton, Richard A; Jackson, Robert B; Morrison, James F; Murray, Brian C; Patakl, Diane E; Skog, Kenneth E

    2011-09-01

    Using forests to mitigate climate change has gained much interest in science and policy discussions. We examine the evidence for carbon benefits, environmental and monetary costs, risks and trade-offs for a variety of activities in three general strategies: (1) land use change to increase forest area (afforestation) and avoid deforestation; (2) carbon management in existing forests; and (3) the use of wood as biomass energy, in place of other building materials, or in wood products for carbon storage. We found that many strategies can increase forest sector carbon mitigation above the current 162-256 Tg C/yr, and that many strategies have co-benefits such as biodiversity, water, and economic opportunities. Each strategy also has trade-offs, risks, and uncertainties including possible leakage, permanence, disturbances, and climate change effects. Because approximately 60% of the carbon lost through deforestation and harvesting from 1700 to 1935 has not yet been recovered and because some strategies store carbon in forest products or use biomass energy, the biological potential for forest sector carbon mitigation is large. Several studies suggest that using these strategies could offset as much as 10-20% of current U.S. fossil fuel emissions. To obtain such large offsets in the United States would require a combination of afforesting up to one-third of cropland or pastureland, using the equivalent of about one-half of the gross annual forest growth for biomass energy, or implementing more intensive management to increase forest growth on one-third of forestland. Such large offsets would require substantial trade-offs, such as lower agricultural production and non-carbon ecosystem services from forests. The effectiveness of activities could be diluted by negative leakage effects and increasing disturbance regimes. Because forest carbon loss contributes to increasing climate risk and because climate change may impede regeneration following disturbance, avoiding

  9. Assessing the Current State of Amber Force Field Modifications for DNA.

    PubMed

    Galindo-Murillo, Rodrigo; Robertson, James C; Zgarbová, Marie; Šponer, Jiří; Otyepka, Michal; Jurečka, Petr; Cheatham, Thomas E

    2016-08-01

    The utility of molecular dynamics (MD) simulations to model biomolecular structure, dynamics, and interactions has witnessed enormous advances in recent years due to the availability of optimized MD software and access to significant computational power, including GPU multicore computing engines and other specialized hardware. This has led researchers to routinely extend conformational sampling times to the microsecond level and beyond. The extended sampling time has allowed the community not only to converge conformational ensembles through complete sampling but also to discover deficiencies and overcome problems with the force fields. Accuracy of the force fields is a key component, along with sampling, toward being able to generate accurate and stable structures of biopolymers. The Amber force field for nucleic acids has been used extensively since the 1990s, and multiple artifacts have been discovered, corrected, and reassessed by different research groups. We present a direct comparison of two of the most recent and state-of-the-art Amber force field modifications, bsc1 and OL15, that focus on accurate modeling of double-stranded DNA. After extensive MD simulations with five test cases and two different water models, we conclude that both modifications are a remarkable improvement over the previous bsc0 force field. Both force field modifications show better agreement when compared to experimental structures. To ensure convergence, the Drew-Dickerson dodecamer (DDD) system was simulated using 100 independent MD simulations, each extended to at least 10 μs, and the independent MD simulations were concatenated into a single 1 ms long trajectory for each combination of force field and water model. This is significantly beyond the time scale needed to converge the conformational ensemble of the internal portions of a DNA helix absent internal base pair opening. Considering all of the simulations discussed in the current work, the MD simulations performed to

  10. Assessing the Current State of Amber Force Field Modifications for DNA

    PubMed Central

    2016-01-01

    The utility of molecular dynamics (MD) simulations to model biomolecular structure, dynamics, and interactions has witnessed enormous advances in recent years due to the availability of optimized MD software and access to significant computational power, including GPU multicore computing engines and other specialized hardware. This has led researchers to routinely extend conformational sampling times to the microsecond level and beyond. The extended sampling time has allowed the community not only to converge conformational ensembles through complete sampling but also to discover deficiencies and overcome problems with the force fields. Accuracy of the force fields is a key component, along with sampling, toward being able to generate accurate and stable structures of biopolymers. The Amber force field for nucleic acids has been used extensively since the 1990s, and multiple artifacts have been discovered, corrected, and reassessed by different research groups. We present a direct comparison of two of the most recent and state-of-the-art Amber force field modifications, bsc1 and OL15, that focus on accurate modeling of double-stranded DNA. After extensive MD simulations with five test cases and two different water models, we conclude that both modifications are a remarkable improvement over the previous bsc0 force field. Both force field modifications show better agreement when compared to experimental structures. To ensure convergence, the Drew–Dickerson dodecamer (DDD) system was simulated using 100 independent MD simulations, each extended to at least 10 μs, and the independent MD simulations were concatenated into a single 1 ms long trajectory for each combination of force field and water model. This is significantly beyond the time scale needed to converge the conformational ensemble of the internal portions of a DNA helix absent internal base pair opening. Considering all of the simulations discussed in the current work, the MD simulations performed to

  11. Physician payment 2008 for interventionalists: current state of health care policy.

    PubMed

    Manchikanti, Laxmaiah; Giordano, James

    2007-09-01

    Physicians in the United States have been affected by significant changes in the pattern(s) of medical practice evolving over the last several decades. These changes include new measures to 1) curb increasing costs, 2) increase access to patient care, 3) improve quality of healthcare, and 4) pay for prescription drugs. Escalating healthcare costs have focused concerns about the financial solvency of Medicare and this in turn has fostered a renewed interest in the economic basis of interventional pain management practices. The provision and systemization of healthcare in North America and several European countries are difficult enterprises to manage irrespective of whether these provisions and systems are privatized (as in the United States) or nationalized or seminationalized (as in Great Britain, Canada, Australia and France). Consequently, while many management options have been put forth, none seem to be optimally geared toward affording healthcare as a maximized individual and social good, and none have been completely enacted. The current physician fee schedule (released on July 12, 2007) includes a 9.9% cut in payment rate. Since the Medicare program was created in 1965, several methods have been used to determine physicians' rate(s) for each covered service. The sustained growth rate (SGR) system, established in 1998, has evoked negative consequences on physician payment(s). Based on the current Medicare expenditure index, practice expenses are projected to increase by 34.5% from 2002 to 2016, whereas, if actual practice inflation is considered, this increase will be 90%. This is in contrast to projected physician payment cuts that are depicted to be 51%. No doubt, this scenario will be devastating to many practices and the US medical community at large. Resolutions to this problem have been offered by MedPAC, the Government Accountability Office, physician organizations, economists, and various other interested groups. In the past, temporary measures have

  12. Improving HIV proteome annotation: new features of BioAfrica HIV Proteomics Resource

    PubMed Central

    Druce, Megan; Hulo, Chantal; Masson, Patrick; Sommer, Paula; Xenarios, Ioannis; Le Mercier, Philippe; De Oliveira, Tulio

    2016-01-01

    The Human Immunodeficiency Virus (HIV) is one of the pathogens that cause the greatest global concern, with approximately 35 million people currently infected with HIV. Extensive HIV research has been performed, generating a large amount of HIV and host genomic data. However, no effective vaccine that protects the host from HIV infection is available and HIV is still spreading at an alarming rate, despite effective antiretroviral (ARV) treatment. In order to develop effective therapies, we need to expand our knowledge of the interaction between HIV and host proteins. In contrast to virus proteins, which often rapidly evolve drug resistance mutations, the host proteins are essentially invariant within all humans. Thus, if we can identify the host proteins needed for virus replication, such as those involved in transporting viral proteins to the cell surface, we have a chance of interrupting viral replication. There is no proteome resource that summarizes this interaction, making research on this subject a difficult enterprise. In order to fill this gap in knowledge, we curated a resource presents detailed annotation on the interaction between the HIV proteome and host proteins. Our resource was produced in collaboration with ViralZone and used manual curation techniques developed by UniProtKB/Swiss-Prot. Our new website also used previous annotations of the BioAfrica HIV-1 Proteome Resource, which has been accessed by approximately 10 000 unique users a year since its inception in 2005. The novel features include a dedicated new page for each HIV protein, a graphic display of its function and a section on its interaction with host proteins. Our new webpages also add information on the genomic location of each HIV protein and the position of ARV drug resistance mutations. Our improved BioAfrica HIV-1 Proteome Resource fills a gap in the current knowledge of biocuration. Database URL: http://www.bioafrica.net/proteomics/HIVproteome.html PMID:27087306

  13. Improving HIV proteome annotation: new features of BioAfrica HIV Proteomics Resource.

    PubMed

    Druce, Megan; Hulo, Chantal; Masson, Patrick; Sommer, Paula; Xenarios, Ioannis; Le Mercier, Philippe; De Oliveira, Tulio

    2016-01-01

    The Human Immunodeficiency Virus (HIV) is one of the pathogens that cause the greatest global concern, with approximately 35 million people currently infected with HIV. Extensive HIV research has been performed, generating a large amount of HIV and host genomic data. However, no effective vaccine that protects the host from HIV infection is available and HIV is still spreading at an alarming rate, despite effective antiretroviral (ARV) treatment. In order to develop effective therapies, we need to expand our knowledge of the interaction between HIV and host proteins. In contrast to virus proteins, which often rapidly evolve drug resistance mutations, the host proteins are essentially invariant within all humans. Thus, if we can identify the host proteins needed for virus replication, such as those involved in transporting viral proteins to the cell surface, we have a chance of interrupting viral replication. There is no proteome resource that summarizes this interaction, making research on this subject a difficult enterprise. In order to fill this gap in knowledge, we curated a resource presents detailed annotation on the interaction between the HIV proteome and host proteins. Our resource was produced in collaboration with ViralZone and used manual curation techniques developed by UniProtKB/Swiss-Prot. Our new website also used previous annotations of the BioAfrica HIV-1 Proteome Resource, which has been accessed by approximately 10 000 unique users a year since its inception in 2005. The novel features include a dedicated new page for each HIV protein, a graphic display of its function and a section on its interaction with host proteins. Our new webpages also add information on the genomic location of each HIV protein and the position of ARV drug resistance mutations. Our improved BioAfrica HIV-1 Proteome Resource fills a gap in the current knowledge of biocuration.Database URL:http://www.bioafrica.net/proteomics/HIVproteome.html. PMID:27087306

  14. Genetic considerations for mollusk production in aquaculture: current state of knowledge

    PubMed Central

    Astorga, Marcela P.

    2014-01-01

    In 2012, world mollusk production in aquaculture reached a volume of 15,171,000 tons, representing 23% of total aquaculture production and positioning mollusks as the second most important category of aquaculture products (fishes are the first). Clams and oysters are the mollusk species with the highest production levels, followed in descending order by mussels, scallops, and abalones. In view of the increasing importance attached to genetic information on aquaculture, which can help with good maintenance and thus the sustainability of production, the present work offers a review of the state of knowledge on genetic and genomic information about mollusks produced in aquaculture. The analysis was applied to mollusks which are of importance for aquaculture, with emphasis on the 5 species with the highest production levels. According to FAO, these are: Japanese clam Ruditapes philippinarum; Pacific oyster Crassostrea gigas; Chilean mussel Mytilus chilensis; Blood clam Anadara granosa and Chinese clam Sinonovacula constricta. To date, the genomes of 5 species of mollusks have been sequenced, only one of which, Crassostrea gigas, coincides with the species with the greatest production in aquaculture. Another important species whose genome has been sequenced is Mytilus galloprovincialis, which is the second most important mussel in aquaculture production, after M. chilensis. Few genetic improvement programs have been reported in comparison with the number reported in fish species. The most commonly investigated species are oysters, with at least 5 genetic improvement programs reported, followed by abalones with 2 programs and mussels with one. The results of this work will establish the current situation with respect to the genetics of mollusks which are of importance for aquaculture production, in order to assist future decisions to ensure the sustainability of these resources. PMID:25540651

  15. Current status of solid waste management in small island developing states: A review.

    PubMed

    Mohee, Romeela; Mauthoor, Sumayya; Bundhoo, Zumar M A; Somaroo, Geeta; Soobhany, Nuhaa; Gunasee, Sanjana

    2015-09-01

    This article reviews the current status of waste management in Small Island Developing States (SIDS) and the challenges that are faced in solid waste management. The waste generation rates of SIDS were compared within the three geographic regions namely Caribbean SIDS, Pacific SIDS and Atlantic, Indian Ocean, Mediterranean and South China (AIMS) SIDS and with countries of the Organisation for Economic Co-Operation and Development (OECD). Only Pacific SIDS had a waste generation rate less than 1kg/capita/day. The waste generation rates for the three SIDS regions averaged 1.29kg/capita/day while that for OECD countries was at a mean value of 1.35kg/capita/day. The waste compositions in the different SIDS regions were almost similar owing to comparable consumption patterns while these differed to a large extent with wastes generated in OECD countries. In SIDS, the major fraction of MSW comprised of organics (44%) followed by recyclables namely paper, plastics, glass and metals (total: 43%). In contrast, MSW in OECD countries consisted mainly of recyclables (43%) followed by organics (37%). This article also reviewed the other functional elements of the waste management systems in SIDS. Several shortcomings were noted in the process of waste collection, transfer and transport namely the fact of having outdated collection vehicles and narrow roads which are inaccessible. Among the waste management practices in SIDS, waste disposal via landfilling, illegal dumping and backyard burning were favoured most of the time at the expense of sustainable waste treatment technologies such as composting, anaerobic digestion and recycling. PMID:26116009

  16. Current state of Czech astronomy popularization and its potential for enhancing science career interest

    NASA Astrophysics Data System (ADS)

    Kříček, Radek

    2015-08-01

    The Czech Republic has a dense net of observatories, astronomical clubs and other activities for both adults and children. Can we use it to improve skills of our pupils and their motivation to choose their career in science? Does the situation in the Czech Republic differ from abroad? What can we improve in the future? These questions were not answered satisfactorily so far. We decided to contribute to solve this issue.We present our survey of current state based mainly on electronic sources and personal dealings. Besides of 56 observatories working with public and many interest clubs, there are other possibilities to meet astronomy. For example, Astronomical Olympiad attracts thousands of pupils across the country each year to solve both theoretical and practical tasks in astronomy. In other projects, children can visit Dark-Sky Parks, design experiments for a stratospheric balloon, observe with CCD or radio devices or build their own rockets.We outline our ongoing project to examine the link between popularization activities and pupils’ or high school students’ attitude toward science and science career. We plan to create a typology of both popularization activities and life stories of people dealing with astronomy. From the methodological point of view, the mixed method design, combining both the qualitative and quantitative approach, will be used to solve the research problems. The basic research plan will be a case study. So far the project is based on interviews with various subjects. We choose people with different life stories, all connected with astronomy or astronomy popularization in some period. We focus on important moments in their career, similarities between subjects, and various types of possible motivation to participate in astronomy-related activities or to study science at university.Future results can be used to help interested organizations such as universities, observatories or astronomical societies. They will be able to work more

  17. How meaning similarity influences ambiguous word processing: the current state of the literature.

    PubMed

    Eddington, Chelsea M; Tokowicz, Natasha

    2015-02-01

    The majority of words in the English language do not correspond to a single meaning, but rather correspond to two or more unrelated meanings (i.e., are homonyms) or multiple related senses (i.e., are polysemes). It has been proposed that the different types of "semantically-ambiguous words" (i.e., words with more than one meaning) are processed and represented differently in the human mind. Several review papers and books have been written on the subject of semantic ambiguity (e.g., Adriaens, Small, Cottrell, & Tanenhaus, 1988; Burgess & Simpson, 1988; Degani & Tokowicz, 2010; Gorfein, 1989, 2001; Simpson, 1984). However, several more recent studies (e.g., Klein & Murphy, 2001; Klepousniotou, 2002; Klepousniotou & Baum, 2007; Rodd, Gaskell, & Marslen-Wilson, 2002) have investigated the role of the semantic similarity between the multiple meanings of ambiguous words on processing and representation, whereas this was not the emphasis of previous reviews of the literature. In this review, we focus on the current state of the semantic ambiguity literature that examines how different types of ambiguous words influence processing and representation. We analyze the consistent and inconsistent findings reported in the literature and how factors such as semantic similarity, meaning/sense frequency, task, timing, and modality affect ambiguous word processing. We discuss the findings with respect to recent parallel distributed processing (PDP) models of ambiguity processing (Armstrong & Plaut, 2008, 2011; Rodd, Gaskell, & Marslen-Wilson, 2004). Finally, we discuss how experience/instance-based models (e.g., Hintzman, 1986; Reichle & Perfetti, 2003) can inform a comprehensive understanding of semantic ambiguity resolution. PMID:24889119

  18. Statistical analysis of clinical prediction rules for rehabilitation interventions: current state of the literature.

    PubMed

    Lubetzky-Vilnai, Anat; Ciol, Marcia; McCoy, Sarah Westcott

    2014-01-01

    Deriving clinical prediction rules (CPRs) to identify specific characteristics of patients who would likely respond to certain interventions has become a research priority in physical rehabilitation. Understanding the appropriate statistical principles and methods of analyses underlying the derivation of CPRs is important for future rehabilitation research and clinical applications. In this article, we aimed to provide an overview of statistical techniques used for the derivation of CPRs to predict success following physical therapy interventions and to generate recommendations for improvements in CPR derivation research and statistical analysis in rehabilitation. We have summarized the current state of CPR intervention-related research by reviewing 26 studies. A common technique was found in most studies and included univariate association of factors with treatment success, stepwise logistic regression to determine the most parsimonious set of predictors for success, and calculation of accuracy statistics (focusing on positive likelihood ratios). We identified several shortcomings related to inadequate ratio of events by number of predictors, lack of standardization regarding acceptable interobserver reliability of predictors, questionable handling of predictors including reliance on univariate analysis and early categorization, and not accounting for dependence and collinearity of predictors in multivariable model construction. Interpretation of the derived CPRs was found to be difficult due to lack of precision of estimates and paradoxical findings when a subset of the predictors yielded a larger positive likelihood ratio than did the full set of predictors. Finally, we make recommendations regarding how to strengthen the use of statistical principles and methods to create consistency across rehabilitation research for CPR derivations. PMID:24036159

  19. Integrated Carbon Observation System (ICOS) ecosystem network: current state and future perspectives

    NASA Astrophysics Data System (ADS)

    Gielen, B.; Op de Beeck, M.; Ceulemans, R.; Janssens, I.; Loustau, D.; Valentini, R.; Papale, D.

    2013-12-01

    Atmospheric concentrations of greenhouse gases (GHG) such as carbon dioxide (CO2) and methane (CH4) are increasing due to emissions related to human activity, affecting the global climate. Natural sinks remove a fraction of the GHG anthropogenic excess at the global level. The characterization of greenhouse gases atmospheric burden and fluxes, both anthropogenic and natural, are needed at the global and regional scale, making use of all available information in an integrated framework. The Integrated Carbon Observation System (ICOS) research infrastructure will address this issue by providing the community with systematic measurements of a suite of atmospheric, terrestrial ecosystem and oceanic measurements. The ecosystem network comprises three station classes, for which variables are collected with different intensity. These stations are well distributed among the major European ecosystem types and cover most climatic zones in Europe. The Ecosystem Thematic Center (ETC) is coordinating the ICOS ecosystem network providing assistance with instruments and methods, testing and developing new measurement techniques and associated processing algorithms; also ensuring a high level of data standardization, uncertainty analysis and database services in coordination with the ICOS carbon portal. The ETC is also coordinating the drafting of the protocols describing in detail how measurements will be collected at all ecosystem stations, in order to guarantee inter comparability. This is done in close collaboration with experts in the field and with the other existing ecological and meteorological networks (NEON, Ameriflux, ICP -forests, MWO, TERN, ...). This presentation will focus on the current state of the ICOS ecosystem network, on the data products and the potential user community.

  20. Proteomics. Tissue-based map of the human proteome.

    PubMed

    Uhlén, Mathias; Fagerberg, Linn; Hallström, Björn M; Lindskog, Cecilia; Oksvold, Per; Mardinoglu, Adil; Sivertsson, Åsa; Kampf, Caroline; Sjöstedt, Evelina; Asplund, Anna; Olsson, IngMarie; Edlund, Karolina; Lundberg, Emma; Navani, Sanjay; Szigyarto, Cristina Al-Khalili; Odeberg, Jacob; Djureinovic, Dijana; Takanen, Jenny Ottosson; Hober, Sophia; Alm, Tove; Edqvist, Per-Henrik; Berling, Holger; Tegel, Hanna; Mulder, Jan; Rockberg, Johan; Nilsson, Peter; Schwenk, Jochen M; Hamsten, Marica; von Feilitzen, Kalle; Forsberg, Mattias; Persson, Lukas; Johansson, Fredric; Zwahlen, Martin; von Heijne, Gunnar; Nielsen, Jens; Pontén, Fredrik

    2015-01-23

    Resolving the molecular details of proteome variation in the different tissues and organs of the human body will greatly increase our knowledge of human biology and disease. Here, we present a map of the human tissue proteome based on an integrated omics approach that involves quantitative transcriptomics at the tissue and organ level, combined with tissue microarray-based immunohistochemistry, to achieve spatial localization of proteins down to the single-cell level. Our tissue-based analysis detected more than 90% of the putative protein-coding genes. We used this approach to explore the human secretome, the membrane proteome, the druggable proteome, the cancer proteome, and the metabolic functions in 32 different tissues and organs. All the data are integrated in an interactive Web-based database that allows exploration of individual proteins, as well as navigation of global expression patterns, in all major tissues and organs in the human body. PMID:25613900