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Sample records for air pathway analysis

  1. ENGINEERING BULLETIN: AIR PATHWAY ANALYSIS

    EPA Science Inventory

    This bulletin presents information on estimating toxic air emissions from Superfund sites. The focus is on the collection of air emmissions data during the site inspection and remedial investigation/feasibility study and the use of these data for the selection or implementation o...

  2. Section 17: Air Pathway- Waste Characteristics and Targets

    EPA Pesticide Factsheets

    HRS Training. the air migration pathway evaluates the likelihood of release of hazardous substances into the atmosphere and how many people and sensitive environments could be exposed to hazardous substances carried in the air, including gases

  3. Dynamical pathway analysis

    PubMed Central

    Xiong, Hao; Choe, Yoonsuck

    2008-01-01

    Background Although a great deal is known about one gene or protein and its functions under different environmental conditions, little information is available about the complex behaviour of biological networks subject to different environmental perturbations. Observing differential expressions of one or more genes between normal and abnormal cells has been a mainstream method of discovering pertinent genes in diseases and therefore valuable drug targets. However, to date, no such method exists for elucidating and quantifying the differential dynamical behaviour of genetic regulatory networks, which can have greater impact on phenotypes than individual genes. Results We propose to redress the deficiency by formulating the functional study of biological networks as a control problem of dynamical systems. We developed mathematical methods to study the stability, the controllability, and the steady-state behaviour, as well as the transient responses of biological networks under different environmental perturbations. We applied our framework to three real-world datasets: the SOS DNA repair network in E. coli under different dosages of radiation, the GSH redox cycle in mice lung exposed to either poisonous air or normal air, and the MAPK pathway in mammalian cell lines exposed to three types of HIV type I Vpr, a wild type and two mutant types; and we found that the three genetic networks exhibited fundamentally different dynamical properties in normal and abnormal cells. Conclusion Difference in stability, relative stability, degrees of controllability, and transient responses between normal and abnormal cells means considerable difference in dynamical behaviours and different functioning of cells. Therefore differential dynamical properties can be a valuable tool in biomedical research. PMID:18221557

  4. Future air pollution in the Shared Socio-economic Pathways

    DOE PAGES

    Rao, Shilpa; Klimont, Zbigniew; Smith, Steven J.; ...

    2016-07-15

    Emissions of air pollutants such as sulfur and nitrogen oxides and particulates have significant health impacts as well as effects on natural and anthropogenic ecosystems. These same emissions also can change atmospheric chemistry and the planetary energy balance, thereby impacting global and regional climate. Long-term scenarios for air pollutant emissions are needed as inputs to global climate and chemistry models, and for analysis linking air pollutant impacts across sectors. In this paper we present methodology and results for air pollutant emissions in Shared Socioeconomic Pathways (SSP) scenarios. We first present a set of three air pollution narratives that describe high,more » central, and low pollution control ambitions over the 21st century. These narratives are then translated into quantitative guidance for use in integrated assessment models. We provide an overview of pollutant emission trajectories under the SSP scenarios. Pollutant emissions in these scenarios cover a wider range than the scenarios used in previous international climate model comparisons. Furthermore, the SSP scenarios provide the opportunity to access a more comprehensive range of future global and regional air quality outcomes.« less

  5. Future air pollution in the Shared Socio-economic Pathways

    SciTech Connect

    Rao, Shilpa; Klimont, Zbigniew; Smith, Steven J.; Van Dingenen, Rita; Dentener, Frank; Bouwman, Lex; Riahi, Keywan; Amann, Markus; Bodirsky, Benjamin Leon; van Vuuren, Detlef P.; Reis, Lara Aleluia; Calvin, Katherine; Drouet, Laurent; Fricko, Oliver; Fujimori, Shinichiro; Gernaat, David; Havlik, Petr; Harmsen, Mathijs; Hasegawa, Tomoko; Heyes, Chris; Hilaire, Jérôme; Luderer, Gunnar; Masui, Toshihiko; Stehfest, Elke; Strefler, Jessica; van der Sluis, Sietske; Tavoni, Massimo

    2016-07-15

    Emissions of air pollutants such as sulfur and nitrogen oxides and particulates have significant health impacts as well as effects on natural and anthropogenic ecosystems. These same emissions also can change atmospheric chemistry and the planetary energy balance, thereby impacting global and regional climate. Long-term scenarios for air pollutant emissions are needed as inputs to global climate and chemistry models, and for analysis linking air pollutant impacts across sectors. In this paper we present methodology and results for air pollutant emissions in Shared Socioeconomic Pathways (SSP) scenarios. We first present a set of three air pollution narratives that describe high, central, and low pollution control ambitions over the 21st century. These narratives are then translated into quantitative guidance for use in integrated assessment models. We provide an overview of pollutant emission trajectories under the SSP scenarios. Pollutant emissions in these scenarios cover a wider range than the scenarios used in previous international climate model comparisons. Furthermore, the SSP scenarios provide the opportunity to access a more comprehensive range of future global and regional air quality outcomes.

  6. Future Air Pollution in the Shared Socio-Economic Pathways

    SciTech Connect

    Rao, Shilpa; Klimont, Zbigniew; Smith, Steven J.; van Dingenen, Rita; Dentener, Frank; Bouwman, Lex; Riahi, Keywan; Amann, Markus; Bodirsky, Benjamin; Van Vuuren, Detlef; Reis, Lara; Calvin, Katherine V.; Drouet, Laurent; Fricko, Oliver; Fujimori, Shinichiro; Gernaat, David; Havlik, Petr; Harmsen, Mathijs; Hasegawa, Tomoko; Heyes, Chris; Hilaire, Jerome; Luderer, Gunnar; Masui, Toshihiko; Stehfest, Eike; Strefler, Jessica; van der Sluis, Sietske; Tavoni, Massimo

    2017-01-01

    Emissions of air pollutants such as sulfur and nitrogen oxides and particulates have significant health impacts as well as effects on natural and anthropogenic ecosystems. These same emissions also can change atmospheric chemistry and the planetary energy balance, thereby impacting global and regional climate. Long-term scenarios for air pollutant emissions are needed as inputs to global climate and chemistry models, and for analysis linking air pollutant impacts across sectors. In this paper we present methodology and results for air pollutant emissions in Shared Socioeconomic Pathways (SSP) scenarios. We first present a set of three air pollution narratives that describe high, central, and low pollution control ambitions over the 21st century. These narratives are then translated into quantitative guidance for use in integrated assessment models. We provide an overview of pollutant emission trajectories under the SSP scenarios. Pollutant emissions in these scenarios cover a wider range than the scenarios used in previous international climate model comparisons. The SSP scenarios provide the opportunity to access a more comprehensive range of future global and regional air quality outcomes.

  7. AIR Model Preflight Analysis

    NASA Technical Reports Server (NTRS)

    Tai, H.; Wilson, J. W.; Maiden, D. L.

    2003-01-01

    The atmospheric ionizing radiation (AIR) ER-2 preflight analysis, one of the first attempts to obtain a relatively complete measurement set of the high-altitude radiation level environment, is described in this paper. The primary thrust is to characterize the atmospheric radiation and to define dose levels at high-altitude flight. A secondary thrust is to develop and validate dosimetric techniques and monitoring devices for protecting aircrews. With a few chosen routes, we can measure the experimental results and validate the AIR model predictions. Eventually, as more measurements are made, we gain more understanding about the hazardous radiation environment and acquire more confidence in the prediction models.

  8. Differential Expression Analysis for Pathways

    PubMed Central

    Haynes, Winston A.; Higdon, Roger; Stanberry, Larissa; Collins, Dwayne; Kolker, Eugene

    2013-01-01

    Life science technologies generate a deluge of data that hold the keys to unlocking the secrets of important biological functions and disease mechanisms. We present DEAP, Differential Expression Analysis for Pathways, which capitalizes on information about biological pathways to identify important regulatory patterns from differential expression data. DEAP makes significant improvements over existing approaches by including information about pathway structure and discovering the most differentially expressed portion of the pathway. On simulated data, DEAP significantly outperformed traditional methods: with high differential expression, DEAP increased power by two orders of magnitude; with very low differential expression, DEAP doubled the power. DEAP performance was illustrated on two different gene and protein expression studies. DEAP discovered fourteen important pathways related to chronic obstructive pulmonary disease and interferon treatment that existing approaches omitted. On the interferon study, DEAP guided focus towards a four protein path within the 26 protein Notch signalling pathway. PMID:23516350

  9. Air Quality Analysis

    EPA Pesticide Factsheets

    This site provides information for air quality data analysts inside and outside EPA. Much of the information is in the form of documented analyses that support the review of the national air qualiyt standards.

  10. Air pocket stability and the imbibition pathway in droplet wetting.

    PubMed

    Chang, Cheng-Chung; Wu, Cyuan-Jhang; Sheng, Yu-Jane; Tsao, Heng-Kwong

    2015-10-07

    The stability of air pockets formed in grooves on a surface is relevant to contact angle hysteresis of droplet wetting and it is investigated by imbibition experiments and surface evolver (SE) simulations. Liquid drops of different wettabilities are placed atop a conical hole on a polymethyl methacrylate (PMMA) substrate. The stability of the air pocket depends on surface wettability. Four kinds of imbibition behaviors ranging from wetting to nonwetting are observed. The imbibition pathway for the kinetically unstable air pocket is observed by using the olive oil droplet. It involves an inward flow of a thin liquid film along the wall of the hole. The accumulation of liquid at the bottom leads to the rise of the air bubble. The energy-barrier profile associated with the imbibition pathway acquired by SE simulations is able to interpret the outcome of imbibition. The advancing and receding contact angles of various liquids on a PMMA substrate with drilled holes are also determined. Their wetting behaviors can be categorized into three types. Our experimental results for substrates with or without fluorination are in good agreement with the theory based on the stability of air pockets.

  11. AIR AND RADON PATHWAY MODELING FOR THE F AREA TANK FARM

    SciTech Connect

    Dixon, K.; Phifer, M.

    2010-07-30

    An air and radon pathways analysis was conducted for the F-Area Tank Farm (FTF) to estimate the flux of volatile radionuclides and radon at the ground surface due to residual waste remaining in the tanks following closure. This analysis was used as the basis to estimate the dose to the maximally exposed individual (MEI) for the air pathway per Curie (Ci) of each radionuclide remaining in the combined FTF waste tanks. For the air pathway analysis, several gaseous radionuclides were considered. These included carbon-14 (C-14), chlorine-36 (Cl-36), iodine-129 (I-129), selenium-79 (Se-79), antimony-125 (Sb-125), tin-126 (Sn-126), tritium (H-3), and technetium-99 (Tc-99). The dose to the MEI was estimated at the SRS Boundary during the 100 year institutional control period. For the 10,000 year post closure compliance period, the dose to the MEI was estimated at the 100 m compliance point. Additionally, the dose to the MEI was estimated at a seepage outcrop located 1600 m from the facility. For the radon pathway analysis, five parent radionuclides and their progeny were analyzed. These parent radionuclides included uranium-238 (U-238), plutonium-238 (Pu-238), uranium-234 (U-234), thorium-230 (Th-230), and radium-226 (Ra-226). The peak flux of radon-222 due to each parent radionuclide was estimated for the simulation period of 10,100 years.

  12. Air Pollution. Part A: Analysis.

    ERIC Educational Resources Information Center

    Ledbetter, Joe O.

    Two facets of the engineering control of air pollution (the analysis of possible problems and the application of effective controls) are covered in this two-volume text. Part A covers Analysis, and Part B, Prevention and Control. (This review is concerned with Part A only.) This volume deals with the terminology, methodology, and symptomatology…

  13. Pathway Analysis: State of the Art.

    PubMed

    García-Campos, Miguel A; Espinal-Enríquez, Jesús; Hernández-Lemus, Enrique

    2015-01-01

    Pathway analysis is a set of widely used tools for research in life sciences intended to give meaning to high-throughput biological data. The methodology of these tools settles in the gathering and usage of knowledge that comprise biomolecular functioning, coupled with statistical testing and other algorithms. Despite their wide employment, pathway analysis foundations and overall background may not be fully understood, leading to misinterpretation of analysis results. This review attempts to comprise the fundamental knowledge to take into consideration when using pathway analysis as a hypothesis generation tool. We discuss the key elements that are part of these methodologies, their capabilities and current deficiencies. We also present an overview of current and all-time popular methods, highlighting different classes across them. In doing so, we show the exploding diversity of methods that pathway analysis encompasses, point out commonly overlooked caveats, and direct attention to a potential new class of methods that attempt to zoom the analysis scope to the sample scale.

  14. Pathway Analysis: State of the Art

    PubMed Central

    García-Campos, Miguel A.; Espinal-Enríquez, Jesús; Hernández-Lemus, Enrique

    2015-01-01

    Pathway analysis is a set of widely used tools for research in life sciences intended to give meaning to high-throughput biological data. The methodology of these tools settles in the gathering and usage of knowledge that comprise biomolecular functioning, coupled with statistical testing and other algorithms. Despite their wide employment, pathway analysis foundations and overall background may not be fully understood, leading to misinterpretation of analysis results. This review attempts to comprise the fundamental knowledge to take into consideration when using pathway analysis as a hypothesis generation tool. We discuss the key elements that are part of these methodologies, their capabilities and current deficiencies. We also present an overview of current and all-time popular methods, highlighting different classes across them. In doing so, we show the exploding diversity of methods that pathway analysis encompasses, point out commonly overlooked caveats, and direct attention to a potential new class of methods that attempt to zoom the analysis scope to the sample scale. PMID:26733877

  15. Final report on the Pathway Analysis Task

    SciTech Connect

    Whicker, F.W.; Kirchner, T.B.

    1993-04-01

    The Pathway Analysis Task constituted one of several multi-laboratory efforts to estimate radiation doses to people, considering all important pathways of exposure, from the testing of nuclear devices at the Nevada Test Site (NTS). The primary goal of the Pathway Analysis Task was to predict radionuclide ingestion by residents of Utah, Nevada, and portions of seven other adjoining western states following radioactive fallout deposition from individual events at the NTS. This report provides comprehensive documentation of the activities and accomplishments of Colorado State University`s Pathway Analysis Task during the entire period of support (1979--91). The history of the project will be summarized, indicating the principal dates and milestones, personnel involved, subcontractors, and budget information. Accomplishments, both primary and auxiliary, will be summarized with general results rather than technical details being emphasized. This will also serve as a guide to the reports and open literature publications produced, where the methodological details and specific results are documented. Selected examples of results on internal dose estimates are provided in this report because the data have not been published elsewhere.

  16. Cleanup standards and pathways analysis methods

    SciTech Connect

    Devgun, J.S.

    1993-09-01

    Remediation of a radioactively contaminated site requires that certain regulatory criteria be met before the site can be released for unrestricted future use. Since the ultimate objective of remediation is to protect the public health and safety, residual radioactivity levels remaining at a site after cleanup must be below certain preset limits or meet acceptable dose or risk criteria. Release of a decontaminated site requires proof that the radiological data obtained from the site meet the regulatory criteria for such a release. Typically release criteria consist of a composite of acceptance limits that depend on the radionuclides, the media in which they are present, and federal and local regulations. In recent years, the US Department of Energy (DOE) has developed a pathways analysis model to determine site-specific soil activity concentration guidelines for radionuclides that do not have established generic acceptance limits. The DOE pathways analysis computer code (developed by Argonne National Laboratory for the DOE) is called RESRAD (Gilbert et al. 1989). Similar efforts have been initiated by the US Nuclear Regulatory Commission (NRC) to develop and use dose-related criteria based on genetic pathways analyses rather than simplistic numerical limits on residual radioactivity. The focus of this paper is radionuclide contaminated soil. Cleanup standards are reviewed, pathways analysis methods are described, and an example is presented in which RESRAD was used to derive cleanup guidelines.

  17. Differential pathway network analysis used to identify key pathways associated with pediatric pneumonia.

    PubMed

    Yang, Jun-Bo; Luo, Rong; Yan, Yan; Chen, Yan

    2016-12-01

    We aimed to identify key pathways to further explore the molecular mechanism underlying pediatric pneumonia using differential pathway network which integrated protein-protein interactions (PPI) data and pathway information. PPI data and pathway information were obtained from STRING and Reactome database, respectively. Next, pathway interactions were identified on the basis of constructing gene-gene interactions randomly, and a weight value computed using Spearman correlation coefficient was assigned to each pathway-pathway interaction, thereby to further detect differential pathway interactions. Subsequently, construction of differential pathway network was implemented using Cytoscope, following by network clustering analysis using ClusterONE. Finally, topological analysis for differential pathway network was performed to identify hub pathway which had top 5% degree distribution. Significantly, 901 pathways were identified to construct pathway interactions. After discarding the pathway interactions with weight value < 1.2, a differential pathway network was constructed, which contained 499 interactions and 347 pathways. Topological analysis showed 17 hub pathways (FGFR1 fusion mutants, molecules associated with elastic fibres, FGFR1 mutant receptor activation, and so on) were identified. Significantly, signaling by FGFR1 fusion mutants and FGFR1 mutant receptor activation simultaneously appeared in two clusters. Molecules associated with elastic fibres existed in one cluster. Accordingly, differential pathway network method might serve as a predictive tool to help us to further understand the development of pediatric pneumonia. FGFR1 fusion mutants, FGFR1 mutant receptor activation, and molecules associated with elastic fibres might play important roles in the progression of pediatric pneumonia.

  18. A novel genetic score approach using instruments to investigate interactions between pathways and environment: application to air pollution.

    PubMed

    Bind, Marie-Abele; Coull, Brent; Suh, Helen; Wright, Robert; Baccarelli, Andrea; Vokonas, Pantel; Schwartz, Joel

    2014-01-01

    Air pollution has been associated with increased systemic inflammation markers. We developed a new pathway analysis approach to investigate whether gene variants within relevant pathways (oxidative stress, endothelial function, and metal processing) modified the association between particulate air pollution and fibrinogen, C-reactive protein (CRP), intercellular adhesion molecule-1 (ICAM-1), and vascular cell adhesion molecule-1 (VCAM-1). Our study population consisted of 822 elderly participants of the Normative Aging Study (1999-2011). To investigate the role of biological mechanisms and to reduce the number of comparisons in the analysis, we created pathway-specific scores using gene variants related to each pathway. To select the most appropriate gene variants, we used the least absolute shrinkage and selection operator (Lasso) to relate independent outcomes representative of each pathway (8-hydroxydeoxyguanosine for oxidative stress, augmentation index for endothelial function, and patella lead for metal processing) to gene variants. A high genetic score corresponds to a higher allelic risk profile. We fit mixed-effects models to examine modification by the genetic score of the weekly air pollution association with the outcome. Among participants with higher genetic scores within the oxidative stress pathway, we observed significant associations between particle number and fibrinogen, while we did not find any association among participants with lower scores (p(interaction) = 0.04). Compared to individuals with low genetic scores of metal processing gene variants, participants with higher scores had greater effects of particle number on fibrinogen (p(interaction) = 0.12), CRP (p(interaction) = 0.02), and ICAM-1 (pinteraction = 0.08). This two-stage penalization method is easy to implement and can be used for large-scale genetic applications.

  19. WikiPathways App for Cytoscape: Making biological pathways amenable to network analysis and visualization.

    PubMed

    Kutmon, Martina; Lotia, Samad; Evelo, Chris T; Pico, Alexander R

    2014-01-01

    In this paper we present the open-source WikiPathways app for Cytoscape ( http://apps.cytoscape.org/apps/wikipathways) that can be used to import biological pathways for data visualization and network analysis. WikiPathways is an open, collaborative biological pathway database that provides fully annotated pathway diagrams for manual download or through web services. The WikiPathways app allows users to load pathways in two different views: as an annotated pathway ideal for data visualization and as a simple network to perform computational analysis. An example pathway and dataset are used to demonstrate the functionality of the WikiPathways app and how they can be combined and used together with other apps. More than 3000 downloads in the first 12 months following its release in August 2013 highlight the importance and adoption of the app in the network biology field.

  20. Catalytic wet air oxidation of phenol with functionalized carbon materials as catalysts: reaction mechanism and pathway.

    PubMed

    Wang, Jianbing; Fu, Wantao; He, Xuwen; Yang, Shaoxia; Zhu, Wanpeng

    2014-08-01

    The development of highly active carbon material catalysts in catalytic wet air oxidation (CWAO) has attracted a great deal of attention. In this study different carbon material catalysts (multi-walled carbon nanotubes, carbon fibers and graphite) were developed to enhance the CWAO of phenol in aqueous solution. The functionalized carbon materials exhibited excellent catalytic activity in the CWAO of phenol. After 60 min reaction, the removal of phenol was nearly 100% over the functionalized multi-walled carbon, while it was only 14% over the purified multi-walled carbon under the same reaction conditions. Carboxylic acid groups introduced on the surface of the functionalized carbon materials play an important role in the catalytic activity in CWAO. They can promote the production of free radicals, which act as strong oxidants in CWAO. Based on the analysis of the intermediates produced in the CWAO reactions, a new reaction pathway for the CWAO of phenol was proposed in this study. There are some differences between the proposed reaction pathway and that reported in the literature. First, maleic acid is transformed directly into malonic acid. Second, acetic acid is oxidized into an unknown intermediate, which is then oxidized into CO2 and H2O. Finally, formic acid and oxalic acid can mutually interconvert when conditions are favorable.

  1. Visual Analysis of Air Traffic Data

    NASA Technical Reports Server (NTRS)

    Albrecht, George Hans; Pang, Alex

    2012-01-01

    In this paper, we present visual analysis tools to help study the impact of policy changes on air traffic congestion. The tools support visualization of time-varying air traffic density over an area of interest using different time granularity. We use this visual analysis platform to investigate how changing the aircraft separation volume can reduce congestion while maintaining key safety requirements. The same platform can also be used as a decision aid for processing requests for unmanned aerial vehicle operations.

  2. Systemic Analysis Approaches for Air Transportation

    NASA Technical Reports Server (NTRS)

    Conway, Sheila

    2005-01-01

    Air transportation system designers have had only limited success using traditional operations research and parametric modeling approaches in their analyses of innovations. They need a systemic methodology for modeling of safety-critical infrastructure that is comprehensive, objective, and sufficiently concrete, yet simple enough to be used with reasonable investment. The methodology must also be amenable to quantitative analysis so issues of system safety and stability can be rigorously addressed. However, air transportation has proven itself an extensive, complex system whose behavior is difficult to describe, no less predict. There is a wide range of system analysis techniques available, but some are more appropriate for certain applications than others. Specifically in the area of complex system analysis, the literature suggests that both agent-based models and network analysis techniques may be useful. This paper discusses the theoretical basis for each approach in these applications, and explores their historic and potential further use for air transportation analysis.

  3. Perfluorinated acids in air, rain, snow, surface runoff, and lakes: relative importance of pathways to contamination of urban lakes.

    PubMed

    Kim, Seung-Kyu; Kannan, Kurunthachalam

    2007-12-15

    Concentrations of perfluorinated acids (PFAs) were measured in various environmental matrices (air, rain, snow, surface runoff water, and lake water) in an urban area, to enable identification of sources and pathways of PFAs to urban water bodies. Total PFA concentrations ranged from 8.28 to 16.0 pg/ m3 (mean 11.3) in bulk air (sum of vapor and particulate phases), 0.91 to 13.2 ng/L (6.19) in rainwater, 0.91 to 23.9 ng/L (7.98) in snow, 1.11-81.8 ng/L (15.1 ng/L) in surface runoff water (SRW), and 9.49 to 35.9 ng/L (21.8) in lake water. Perfluorooctanoic acid (PFOA) was the predominant compound, accounting for > 35% of the total PFA concentrations, in all environmental matrices analyzed. Concentrations and relative compositions of PFAs in SRW were similar to those found for urban lakes. SRW contributes to contamination by PFOA in urban lakes. The measured concentration ratios of FTOH to PFOA in air were 1-2 orders of magnitude lower than the ratios calculated based on an assumption of exclusive atmospheric oxidation of FTOHs. Nevertheless, the mass balance analysis suggested the presence of an unknown input pathway that could contribute to a significant amount of total PFOA loadings to the lake. Flux estimates of PFOA at the air-water interface in the urban lake suggest net volatilization from water.

  4. Ozone and Trace Gas Trends in the UK and Links to Changing Air Mass Pathways

    NASA Astrophysics Data System (ADS)

    Fleming, Z.; Monks, P. S.; Reeves, C.; Bohnenstengel, S.

    2014-12-01

    Trace gas measurements from UK measurement sites on the North Sea coast and in central London reveal a complicated relationship between NO2, CO, hydrocarbons and ozone. Due to the location of the sites, they receive air masses from the UK, Europe, the North sea, Scandinavia and the Arctic and Atlantic Seas and any seasonality is hard to discern. The transport pathway of air masses that can change on an hourly timescale clearly influences the trace gas levels. Investigations into how the transport pathways have changed over the years, using the NAME dispersion model try to elucidate whether it is the 'where' (transport pathway) or the 'what' (trace gas emissions) that is leading to the ozone trends recorded over the past few years.

  5. Pathway Analysis Incorporating Protein-Protein Interaction Networks Identified Candidate Pathways for the Seven Common Diseases

    PubMed Central

    Lin, Peng-Lin; Yu, Ya-Wen

    2016-01-01

    Pathway analysis has become popular as a secondary analysis strategy for genome-wide association studies (GWAS). Most of the current pathway analysis methods aggregate signals from the main effects of single nucleotide polymorphisms (SNPs) in genes within a pathway without considering the effects of gene-gene interactions. However, gene-gene interactions can also have critical effects on complex diseases. Protein-protein interaction (PPI) networks have been used to define gene pairs for the gene-gene interaction tests. Incorporating the PPI information to define gene pairs for interaction tests within pathways can increase the power for pathway-based association tests. We propose a pathway association test, which aggregates the interaction signals in PPI networks within a pathway, for GWAS with case-control samples. Gene size is properly considered in the test so that genes do not contribute more to the test statistic simply due to their size. Simulation studies were performed to verify that the method is a valid test and can have more power than other pathway association tests in the presence of gene-gene interactions within a pathway under different scenarios. We applied the test to the Wellcome Trust Case Control Consortium GWAS datasets for seven common diseases. The most significant pathway is the chaperones modulate interferon signaling pathway for Crohn’s disease (p-value = 0.0003). The pathway modulates interferon gamma, which induces the JAK/STAT pathway that is involved in Crohn’s disease. Several other pathways that have functional implications for the seven diseases were also identified. The proposed test based on gene-gene interaction signals in PPI networks can be used as a complementary tool to the current existing pathway analysis methods focusing on main effects of genes. An efficient software implementing the method is freely available at http://puppi.sourceforge.net. PMID:27622767

  6. The Pathway for Oxygen: Tutorial Modelling on Oxygen Transport from Air to Mitochondrion: The Pathway for Oxygen.

    PubMed

    Bassingthwaighte, James B; Raymond, Gary M; Dash, Ranjan K; Beard, Daniel A; Nolan, Margaret

    2016-01-01

    The 'Pathway for Oxygen' is captured in a set of models describing quantitative relationships between fluxes and driving forces for the flux of oxygen from the external air source to the mitochondrial sink at cytochrome oxidase. The intervening processes involve convection, membrane permeation, diffusion of free and heme-bound O2 and enzymatic reactions. While this system's basic elements are simple: ventilation, alveolar gas exchange with blood, circulation of the blood, perfusion of an organ, uptake by tissue, and consumption by chemical reaction, integration of these pieces quickly becomes complex. This complexity led us to construct a tutorial on the ideas and principles; these first PathwayO2 models are simple but quantitative and cover: (1) a 'one-alveolus lung' with airway resistance, lung volume compliance, (2) bidirectional transport of solute gasses like O2 and CO2, (3) gas exchange between alveolar air and lung capillary blood, (4) gas solubility in blood, and circulation of blood through the capillary syncytium and back to the lung, and (5) blood-tissue gas exchange in capillaries. These open-source models are at Physiome.org and provide background for the many respiratory models there.

  7. Pathway Cross-Talk Analysis in Detecting Significant Pathways in Barrett’s Esophagus Patients

    PubMed Central

    Xu, Zhengyuan; Yan, Yan; He, Jian; Shan, Xinfang; Wu, Weiguo

    2017-01-01

    Background The pathological mechanism of Barrett’s esophagus (BE) is still unclear. In the present study, pathway cross-talks were analyzed to identify hub pathways for BE, with the purpose of finding an efficient and cost-effective detection method to discover BE at its early stage and take steps to prevent its progression. Material/Methods We collected and preprocessed gene expression profile data, original pathway data, and protein-protein interaction (PPI) data. Then, we constructed a background pathway cross-talk network (BPCN) based on the original pathway data and PPI data, and a disease pathway cross-talk network (DPCN) based on the differential pathways between the PPI data and the BE and normal control. Finally, a comprehensive analysis was conducted on these 2 networks to identify hub pathway cross-talks for BE, so as to better understand the pathological mechanism of BE from the pathway level. Results A total of 12 411 genes, 300 pathways (6919 genes), and 787 896 PPI interactions (16 730 genes) were separately obtained from their own databases. Then, we constructed a BPCN with 300 nodes (42 293 interactions) and a DPCN with 296 nodes (15 073 interactions). We identified 4 hub pathways: AMP signaling pathway, cGMP-PKG signaling pathway, natural killer cell-mediated cytotoxicity, and osteoclast differentiation. We found that these pathways might play important roles during the occurrence and development of BE. Conclusions We predicted that these pathways (such as AMP signaling pathway and cAMP signaling pathway) could be used as potential biomarkers for early diagnosis and therapy of BE. PMID:28263955

  8. Pathway-based analysis of microarray and RNAseq data using Pathway Processor 2.0.

    PubMed

    Beltrame, Luca; Bianco, Luca; Fontana, Paolo; Cavalieri, Duccio

    2013-03-01

    The constant improvement of high-throughput technologies has led to a great increase in generated data per single experiment. Pathway analysis is a widespread method to understand experimental results at the system level. Pathway Processor 2.0 is an upgrade over the original Pathway Processor program developed in 2002, extended to support more species, analysis methods, and RNAseq data in addition to microarrays through a simple Web-based interface. The tool can perform two different types of analysis: the first covers the traditional Fisher's Test used by Pathway Processor and topology-aware analyses, which take into account the propagation of changes over the whole structure of a pathway, and the second is a new pathway-based method to investigate differences between phenotypes of interest. Common problems and troubleshooting are also discussed.

  9. Modeling air pollution in the Tracking and Analysis Framework (TAF)

    SciTech Connect

    Shannon, J.D.

    1998-12-31

    The Tracking and Analysis Framework (TAF) is a set of interactive computer models for integrated assessment of the Acid Rain Provisions (Title IV) of the 1990 Clean Air Act Amendments. TAF is designed to execute in minutes on a personal computer, thereby making it feasible for a researcher or policy analyst to examine quickly the effects of alternate modeling assumptions or policy scenarios. Because the development of TAF involves researchers in many different disciplines, TAF has been given a modular structure. In most cases, the modules contain reduced-form models that are based on more complete models exercised off-line. The structure of TAF as of December 1996 is shown. Both the Atmospheric Pathways Module produce estimates for regional air pollution variables.

  10. Estimating human exposure through multiple pathways from air, water, and soil.

    PubMed

    McKone, T E; Daniels, J I

    1991-02-01

    This paper describes a set of multipathway, multimedia models for estimating potential human exposure to environmental contaminants. The models link concentrations of an environmental contaminant in air, water, and soil to human exposure through inhalation, ingestion, and dermal-contact routes. The relationship between concentration of a contaminant in an environmental medium and human exposure is determined with pathway exposure factors (PEFs). A PEF is an algebraic expression that incorporates information on human physiology and lifestyle together with models of environmental partitioning and translates a concentration (i.e., mg/m3 in air, mg/liter in water, or mg/kg in soil) into a lifetime-equivalent chronic daily intake (CDI) in mg/kg-day. Human, animal, and environmental data used in calculating PEFs are presented and discussed. Generalized PEFs are derived for air----inhalation, air----ingestion, water----inhalation, water----ingestion, water----dermal uptake, soil----inhalation, soil----ingestion, and soil----dermal uptake pathways. To illustrate the application of the PEF expressions, we apply them to soil-based contamination of multiple environmental media by arsenic, tetrachloroethylene (PCE), and trinitrotoluene (TNT).

  11. Reactome Pathway Analysis to Enrich Biological Discovery in Proteomics Datasets

    PubMed Central

    Haw, Robin; Hermjakob, Henning; D’Eustachio, Peter; Stein, Lincoln

    2012-01-01

    Reactome (http://www.reactome.org) is an open source, expert-authored, peer-reviewed, manually curated database of reactions, pathways and biological processes. We provide an intuitive web-based user interface to pathway knowledge and a suite of data analysis tools. The Pathway Browser is a Systems Biology Graphical Notation (SBGN)-like visualization system that supports manual navigation of pathways by zooming, scrolling and event highlighting, and that exploits PSI Common Query Interface (PSIQUIC) web services to overlay pathways with molecular interaction data from the Reactome Functional Interaction (FI) Network and interaction databases such as IntAct, ChEMBL, and BioGRID. Pathway and Expression Analysis tools employ web services to provide ID mapping, pathway assignment and over-representation analysis of user-supplied datasets. By applying Ensembl Compara to curated human proteins and reactions, Reactome generates pathway inferences for 20 other species. The Species Comparison tool provides a summary of results for each of these species as a table showing numbers of orthologous proteins found by pathway from which users can navigate to inferred details for specific proteins and reactions. Reactome’s diverse pathway knowledge and suite of data analysis tools provide a platform for data mining, modeling and the analysis of large-scale proteomics datasets. PMID:21751369

  12. General aviation air traffic pattern safety analysis

    NASA Technical Reports Server (NTRS)

    Parker, L. C.

    1973-01-01

    A concept is described for evaluating the general aviation mid-air collision hazard in uncontrolled terminal airspace. Three-dimensional traffic pattern measurements were conducted at uncontrolled and controlled airports. Computer programs for data reduction, storage retrieval and statistical analysis have been developed. Initial general aviation air traffic pattern characteristics are presented. These preliminary results indicate that patterns are highly divergent from the expected standard pattern, and that pattern procedures observed can affect the ability of pilots to see and avoid each other.

  13. Air Force Materiel Command Reorganization Analysis

    DTIC Science & Technology

    2012-01-01

    Shelton, John A. Ausink, Chelsea Kaihoi Duran, Robert G. DeFeo, David W. George, Raymond E. Conley, Bernard Fox, Jerry M. Sollinger PROJECT AIR FORCE...Programs, and Analysis Director- ate (AFMC/A8/9); John Steenbock of the AFMC Manpower and Personnel Direc- torate (AFMC/A1); and others at Headquarters...Secretary of the Air Force for Logistics (SAF/IEL); Col John Dolan in the Office of the Legislative Liaison (SAF/LL); Col Jeffrey Morgan in the in

  14. Air pathway effects of nuclear materials production at the Hanford Site, 1983 to 1992

    SciTech Connect

    Patton, G.W.; Cooper, A.T.

    1993-10-01

    This report describes the air pathway effects of Hanford Site operations from 1983 to 1992 on the local environment by summarizing the air concentrations of selected radionuclides at both onsite and offsite locations, comparing trends in environment concentrations to changing facility emissions, and briefly describing trends in the radiological dose to the hypothetical maximally exposed member of the public. The years 1983 to 1992 represent the last Hanford Site plutonium production campaign, and this report deals mainly with the air pathway effects from the 200 Areas, in which the major contributors to radiological emissions were located. An additional purpose for report was to review the environmental data for a long period of time to provide insight not available in an annual report format. The sampling and analytical systems used by the Surface Environmental Surveillance Project (SESP) to collect air samples during the period of this report were sufficiently sensitive to observe locally elevated concentrations of selected radionuclides near onsite source of emission as well as observing elevated levels, compared to distant locations, of some radionuclides at the down wind perimeter. The US DOE Derived Concentration Guides (DCGs) for airborne radionuclides were not exceeded for any air sample collected during 1983 to 1992, with annual average concentrations of all radionuclides at the downwind perimeter being considerably below the DCG values. Air emissions at the Hanford Site during the period of this report were dominated by releases from the PUREX Plant, with {sup 85}Kr being the major release on a curie basis and {sup 129}I being the major release on a radiological dose basis. The estimated potential radiological dose from Hanford Site point source emissions to the hypothetical maximally exposed individual (MEI) ranged from 0. 02 to 0.22 mrem/yr (effective dose equivalent), which is well below the DOE radiation limit to the public of 100 mrem/yr.

  15. Separate enrichment analysis of pathways for up- and downregulated genes.

    PubMed

    Hong, Guini; Zhang, Wenjing; Li, Hongdong; Shen, Xiaopei; Guo, Zheng

    2014-03-06

    Two strategies are often adopted for enrichment analysis of pathways: the analysis of all differentially expressed (DE) genes together or the analysis of up- and downregulated genes separately. However, few studies have examined the rationales of these enrichment analysis strategies. Using both microarray and RNA-seq data, we show that gene pairs with functional links in pathways tended to have positively correlated expression levels, which could result in an imbalance between the up- and downregulated genes in particular pathways. We then show that the imbalance could greatly reduce the statistical power for finding disease-associated pathways through the analysis of all-DE genes. Further, using gene expression profiles from five types of tumours, we illustrate that the separate analysis of up- and downregulated genes could identify more pathways that are really pertinent to phenotypic difference. In conclusion, analysing up- and downregulated genes separately is more powerful than analysing all of the DE genes together.

  16. Air exchange rates and alternative vapor entry pathways to inform vapor intrusion exposure risk assessments.

    PubMed

    Reichman, Rivka; Roghani, Mohammadyousef; Willett, Evan J; Shirazi, Elham; Pennell, Kelly G

    2016-11-12

    Vapor intrusion (VI) is a term used to describe indoor air (IA) contamination that occurs due to the migration of chemical vapors in the soil and groundwater. The overall vapor transport process depends on several factors such as contaminant source characteristics, subsurface conditions, building characteristics, and general site conditions. However, the classic VI conceptual model does not adequately account for the physics of airflow around and inside a building and does not account for chemical emissions from alternative "preferential" pathways (e.g. sewers and other utility connections) into IA spaces. This mini-review provides information about recent research related to building air exchange rates (AERs) and alternative pathways to improve the accuracy of VI exposure risk assessment practices. First, results from a recently published AER study for residential homes across the United States (US) are presented and compared to AERs recommended by the US Environmental Protection Agency (USEPA). The comparison shows considerable differences in AERs when season, location, building age, and other factors are considered. These differences could directly impact VI assessments by influencing IA concentration measurements. Second, a conceptual model for sewer gas entry into buildings is presented and a summary of published field studies is reported. The results of the field studies suggest that alternative pathways for vapors to enter indoor spaces warrant consideration. Ultimately, the information presented in this mini-review can be incorporated into a multiple-lines-of-evidence approach for assessing site-specific VI exposure risks.

  17. Pollutant transfer through air and water pathways in an urban environment

    SciTech Connect

    Brown, M.; Burian, S.; McPherson, T.; Streit, G.; Costigan, K.; Greene, B.

    1998-12-31

    The authors are attempting to simulate the transport and fate of pollutants through air and water pathways in an urban environment. This cross-disciplinary study involves linking together models of mesoscale meteorology, air pollution chemistry and deposition, urban runoff and stormwater transport, water quality, and wetland chemistry and biology. The authors are focusing on the transport and fate of nitrogen species because (1) they track through both air and water pathways, (2) the physics, chemistry, and biology of the complete cycle is not well understood, and (3) they have important health, local ecosystem, and global climate implications. The authors will apply their linked modeling system to the Los Angeles basin, following the fate of nitrates from their beginning as nitrate-precursors produced by auto emissions and industrial processes, tracking their dispersion and chemistry as they are transported by regional winds and eventually wet or dry deposit on the ground, tracing their path as they are entrained into surface water runoff during rain events and carried into the stormwater system, and then evaluating their impact on receiving water bodies such as wetlands where biologically-mediated chemical reactions take place. In this paper, the authors wish to give an overview of the project and at the conference show preliminary results.

  18. Environmental Analysis of the Air Bending Process

    NASA Astrophysics Data System (ADS)

    Kellens, Karel; Dewulf, Wim; Duflou, Joost R.

    2011-05-01

    This paper presents the results of a data collection effort, allowing to assess the overall environmental impact of the air bending process using the CO2PE!-Methodology. First the different modes of the air bending process are investigated, including both productive and non-productive modes. In particular consumption of electric power is recorded for the different modes. Subsequently, time studies allow determining the importance of productive and nonproductive modes of the involved process. The study demonstrates that the influence of standby losses can be substantial. In addition to life cycle analysis, in depth process analysis also provides insight in achievable environmental impact reducing measures towards machine tool builders and eco-design recommendations for product developers. The energy consumption of three different machine tool architectures are analysed and compared within this paper.

  19. A Return on Investment Analysis of Air Force Officer Accessions

    DTIC Science & Technology

    2014-02-13

    AIR WAR COLLEGE AIR UNIVERSITY A RETURN ON INVESTMENT ANALYSIS OF AIR FORCE OFFICER ACCESSIONS by David O’Malley, LtCol, USAF...Lieutenant Colonel David O’Malley is assigned to the Air War College , Air University, Maxwell AFB, AL. Before attending the Air War College , LtCol O’Malley...the candidate’s junior and senior years of college , and a non-scholarship program. 3 Upon graduating from college , all ROTC candidates receive a four

  20. Incorporating principal component analysis into air quality ...

    EPA Pesticide Factsheets

    The efficacy of standard air quality model evaluation techniques is becoming compromised as the simulation periods continue to lengthen in response to ever increasing computing capacity. Accordingly, the purpose of this paper is to demonstrate a statistical approach called Principal Component Analysis (PCA) with the intent of motivating its use by the evaluation community. One of the main objectives of PCA is to identify, through data reduction, the recurring and independent modes of variations (or signals) within a very large dataset, thereby summarizing the essential information of that dataset so that meaningful and descriptive conclusions can be made. In this demonstration, PCA is applied to a simple evaluation metric – the model bias associated with EPA's Community Multi-scale Air Quality (CMAQ) model when compared to weekly observations of sulfate (SO42−) and ammonium (NH4+) ambient air concentrations measured by the Clean Air Status and Trends Network (CASTNet). The advantages of using this technique are demonstrated as it identifies strong and systematic patterns of CMAQ model bias across a myriad of spatial and temporal scales that are neither constrained to geopolitical boundaries nor monthly/seasonal time periods (a limitation of many current studies). The technique also identifies locations (station–grid cell pairs) that are used as indicators for a more thorough diagnostic evaluation thereby hastening and facilitating understanding of the prob

  1. WholePathwayScope: a comprehensive pathway-based analysis tool for high-throughput data

    PubMed Central

    Yi, Ming; Horton, Jay D; Cohen, Jonathan C; Hobbs, Helen H; Stephens, Robert M

    2006-01-01

    Background Analysis of High Throughput (HTP) Data such as microarray and proteomics data has provided a powerful methodology to study patterns of gene regulation at genome scale. A major unresolved problem in the post-genomic era is to assemble the large amounts of data generated into a meaningful biological context. We have developed a comprehensive software tool, WholePathwayScope (WPS), for deriving biological insights from analysis of HTP data. Result WPS extracts gene lists with shared biological themes through color cue templates. WPS statistically evaluates global functional category enrichment of gene lists and pathway-level pattern enrichment of data. WPS incorporates well-known biological pathways from KEGG (Kyoto Encyclopedia of Genes and Genomes) and Biocarta, GO (Gene Ontology) terms as well as user-defined pathways or relevant gene clusters or groups, and explores gene-term relationships within the derived gene-term association networks (GTANs). WPS simultaneously compares multiple datasets within biological contexts either as pathways or as association networks. WPS also integrates Genetic Association Database and Partial MedGene Database for disease-association information. We have used this program to analyze and compare microarray and proteomics datasets derived from a variety of biological systems. Application examples demonstrated the capacity of WPS to significantly facilitate the analysis of HTP data for integrative discovery. Conclusion This tool represents a pathway-based platform for discovery integration to maximize analysis power. The tool is freely available at . PMID:16423281

  2. Mediation pathways and effects of green structures on respiratory mortality via reducing air pollution

    PubMed Central

    Shen, Yu-Sheng; Lung, Shih-Chun Candice

    2017-01-01

    Previous studies have shown both health and environmental benefits of green spaces, especially in moderating temperature and reducing air pollution. However, the characteristics of green structures have been overlooked in previous investigations. In addition, the mediation effects of green structures on respiratory mortality have not been assessed. This study explores the potential mediation pathways and effects of green structure characteristics on respiratory mortality through temperature, primary and secondary air pollutants separately using partial least squares model with data from Taiwan. The measurable characteristics of green structure include the largest patch percentage, landscape proportion, aggregation, patch distance, and fragmentation. The results showed that mortality of pneumonia and chronic lower respiratory diseases could be reduced by minimizing fragmentation and increasing the largest patch percentage of green structure, and the mediation effects are mostly through reducing air pollutants rather than temperature. Moreover, a high proportion of but fragmented green spaces would increase secondary air pollutants and enhance health risks; demonstrating the deficiency of traditional greening policy with primary focus on coverage ratio. This is the first research focusing on mediation effects of green structure characteristics on respiratory mortality, revealing that appropriate green structure planning can be a useful complementary strategy in environmental health management. PMID:28230108

  3. Mediation pathways and effects of green structures on respiratory mortality via reducing air pollution

    NASA Astrophysics Data System (ADS)

    Shen, Yu-Sheng; Lung, Shih-Chun Candice

    2017-02-01

    Previous studies have shown both health and environmental benefits of green spaces, especially in moderating temperature and reducing air pollution. However, the characteristics of green structures have been overlooked in previous investigations. In addition, the mediation effects of green structures on respiratory mortality have not been assessed. This study explores the potential mediation pathways and effects of green structure characteristics on respiratory mortality through temperature, primary and secondary air pollutants separately using partial least squares model with data from Taiwan. The measurable characteristics of green structure include the largest patch percentage, landscape proportion, aggregation, patch distance, and fragmentation. The results showed that mortality of pneumonia and chronic lower respiratory diseases could be reduced by minimizing fragmentation and increasing the largest patch percentage of green structure, and the mediation effects are mostly through reducing air pollutants rather than temperature. Moreover, a high proportion of but fragmented green spaces would increase secondary air pollutants and enhance health risks; demonstrating the deficiency of traditional greening policy with primary focus on coverage ratio. This is the first research focusing on mediation effects of green structure characteristics on respiratory mortality, revealing that appropriate green structure planning can be a useful complementary strategy in environmental health management.

  4. Aqueous reactive species induced by a surface air discharge: Heterogeneous mass transfer and liquid chemistry pathways

    NASA Astrophysics Data System (ADS)

    Liu, D. X.; Liu, Z. C.; Chen, C.; Yang, A. J.; Li, D.; Rong, M. Z.; Chen, H. L.; Kong, M. G.

    2016-04-01

    Plasma-liquid interaction is a critical area of plasma science and a knowledge bottleneck for many promising applications. In this paper, the interaction between a surface air discharge and its downstream sample of deionized water is studied with a system-level computational model, which has previously reached good agreement with experimental results. Our computational results reveal that the plasma-induced aqueous species are mainly H+, nitrate, nitrite, H2O2 and O3. In addition, various short-lived aqueous species are also induced, regardless whether they are generated in the gas phase first. The production/loss pathways for aqueous species are quantified for an air gap width ranging from 0.1 to 2 cm, of which heterogeneous mass transfer and liquid chemistry are found to play a dominant role. The short-lived reactive oxygen species (ROS) and reactive nitrogen species (RNS) are strongly coupled in liquid-phase reactions: NO3 is an important precursor for short-lived ROS, and in turn OH, O2- and HO2 play a crucial role for the production of short-lived RNS. Also, heterogeneous mass transfer depends strongly on the air gap width, resulting in two distinct scenarios separated by a critical air gap of 0.5 cm. The liquid chemistry is significantly different in these two scenarios.

  5. Mediation pathways and effects of green structures on respiratory mortality via reducing air pollution.

    PubMed

    Shen, Yu-Sheng; Lung, Shih-Chun Candice

    2017-02-23

    Previous studies have shown both health and environmental benefits of green spaces, especially in moderating temperature and reducing air pollution. However, the characteristics of green structures have been overlooked in previous investigations. In addition, the mediation effects of green structures on respiratory mortality have not been assessed. This study explores the potential mediation pathways and effects of green structure characteristics on respiratory mortality through temperature, primary and secondary air pollutants separately using partial least squares model with data from Taiwan. The measurable characteristics of green structure include the largest patch percentage, landscape proportion, aggregation, patch distance, and fragmentation. The results showed that mortality of pneumonia and chronic lower respiratory diseases could be reduced by minimizing fragmentation and increasing the largest patch percentage of green structure, and the mediation effects are mostly through reducing air pollutants rather than temperature. Moreover, a high proportion of but fragmented green spaces would increase secondary air pollutants and enhance health risks; demonstrating the deficiency of traditional greening policy with primary focus on coverage ratio. This is the first research focusing on mediation effects of green structure characteristics on respiratory mortality, revealing that appropriate green structure planning can be a useful complementary strategy in environmental health management.

  6. Aqueous reactive species induced by a surface air discharge: Heterogeneous mass transfer and liquid chemistry pathways

    PubMed Central

    Liu, D. X.; Liu, Z. C.; Chen, C.; Yang, A. J.; Li, D.; Rong, M. Z.; Chen, H. L.; Kong, M. G.

    2016-01-01

    Plasma-liquid interaction is a critical area of plasma science and a knowledge bottleneck for many promising applications. In this paper, the interaction between a surface air discharge and its downstream sample of deionized water is studied with a system-level computational model, which has previously reached good agreement with experimental results. Our computational results reveal that the plasma-induced aqueous species are mainly H+, nitrate, nitrite, H2O2 and O3. In addition, various short-lived aqueous species are also induced, regardless whether they are generated in the gas phase first. The production/loss pathways for aqueous species are quantified for an air gap width ranging from 0.1 to 2 cm, of which heterogeneous mass transfer and liquid chemistry are found to play a dominant role. The short-lived reactive oxygen species (ROS) and reactive nitrogen species (RNS) are strongly coupled in liquid-phase reactions: NO3 is an important precursor for short-lived ROS, and in turn OH, O2− and HO2 play a crucial role for the production of short-lived RNS. Also, heterogeneous mass transfer depends strongly on the air gap width, resulting in two distinct scenarios separated by a critical air gap of 0.5 cm. The liquid chemistry is significantly different in these two scenarios. PMID:27033381

  7. Pathway Analysis in Attention Deficit Hyperactivity Disorder: An Ensemble Approach

    PubMed Central

    Mooney, Michael A.; McWeeney, Shannon K.; Faraone, Stephen V.; Hinney, Anke; Hebebrand, Johannes; Nigg, Joel T.; Wilmot, Beth

    2016-01-01

    Despite a wealth of evidence for the role of genetics in attention deficit hyperactivity disorder (ADHD), specific and definitive genetic mechanisms have not been identified. Pathway analyses, a subset of gene-set analyses, extend the knowledge gained from genome-wide association studies (GWAS) by providing functional context for genetic associations. However, there are numerous methods for association testing of gene sets and no real consensus regarding the best approach. The present study applied six pathway analysis methods to identify pathways associated with ADHD in two GWAS datasets from the Psychiatric Genomics Consortium. Methods that utilize genotypes to model pathway-level effects identified more replicable pathway associations than methods using summary statistics. In addition, pathways implicated by more than one method were significantly more likely to replicate. A number of brain-relevant pathways, such as RhoA signaling, glycosaminoglycan biosynthesis, fibroblast growth factor receptor activity, and pathways containing potassium channel genes, were nominally significant by multiple methods in both datasets. These results support previous hypotheses about the role of regulation of neurotransmitter release, neurite outgrowth and axon guidance in contributing to the ADHD phenotype and suggest the value of cross-method convergence in evaluating pathway analysis results. PMID:27004716

  8. Pathway analysis in attention deficit hyperactivity disorder: An ensemble approach.

    PubMed

    Mooney, Michael A; McWeeney, Shannon K; Faraone, Stephen V; Hinney, Anke; Hebebrand, Johannes; Nigg, Joel T; Wilmot, Beth

    2016-09-01

    Despite a wealth of evidence for the role of genetics in attention deficit hyperactivity disorder (ADHD), specific and definitive genetic mechanisms have not been identified. Pathway analyses, a subset of gene-set analyses, extend the knowledge gained from genome-wide association studies (GWAS) by providing functional context for genetic associations. However, there are numerous methods for association testing of gene sets and no real consensus regarding the best approach. The present study applied six pathway analysis methods to identify pathways associated with ADHD in two GWAS datasets from the Psychiatric Genomics Consortium. Methods that utilize genotypes to model pathway-level effects identified more replicable pathway associations than methods using summary statistics. In addition, pathways implicated by more than one method were significantly more likely to replicate. A number of brain-relevant pathways, such as RhoA signaling, glycosaminoglycan biosynthesis, fibroblast growth factor receptor activity, and pathways containing potassium channel genes, were nominally significant by multiple methods in both datasets. These results support previous hypotheses about the role of regulation of neurotransmitter release, neurite outgrowth and axon guidance in contributing to the ADHD phenotype and suggest the value of cross-method convergence in evaluating pathway analysis results. © 2016 Wiley Periodicals, Inc.

  9. Draft Air Pathway Report: Phase 1 of the Hanford Environmental Dose Reconstruction Project

    SciTech Connect

    Not Available

    1990-07-20

    This report summarizes the air pathway portion of the first phase of the Hanford Environmental Dose Reconstruction (HEDR) Project, conducted by Battelle staff at the Pacific Northwest Laboratory under the direction of an independent Technical Steering Panel. The HEDR Project is estimating historical radiation doses that could have been received by populations near the Department of Energy's Hanford Site, in southeastern Washington State. Phase 1 of the air-pathway dose reconstruction sought to determine whether dose estimates could be calculated for populations in the 10 counties nearest the Hanford Site from atmospheric releases of iodine-131 from the site from 1944--1947. Phase 1 demonstrated the following: HEDR-calculated source-term estimates of iodine-131 releases to the atmosphere were within 20% of previously published estimates; calculated vegetation concentrations of iodine-131 agree well with previously published measurements; the highest of the Phase 1 preliminary dose estimates to the thyroid are consistent with independent, previously published estimates of doses to maximally exposed individuals; and relatively crude, previously published measurements of thyroid burdens for Hanford workers are in the range of average burdens that the HEDR model estimated for similar reference individuals'' for the period 1944--1947. 4 refs., 10 figs., 9 tabs.

  10. Air pathway report: Phase I of the Hanford Environmental Dose Reconstruction Project

    SciTech Connect

    Not Available

    1991-07-01

    Phase 1 of the air-pathway portion of the Hanford Environmental Dose Reconstruction (HEDR) Project sought to determine whether dose estimates could be calculated for populations in the 10 counties nearest the Hanford Site from atmospheric releases of iodine-131 from the site from 1944--1947. Phase 1 demonstrated the following: HEDR-calculated source-term estimates of iodine-131 releases to the atmosphere were within 20% of previously published estimates; calculated vegetation concentrations of iodine-131 agree well with previously published measurements; the highest of the Phase 1 preliminary dose estimates to the thyroid are consistent with independent, previously published estimates of doses to maximally exposed individuals; and, relatively crude, previously published measurements of thyroid burdens for Hanford workers are in the range of average burdens that the HEDR model estimated for similar reference individuals'' for the period 1944--1947. Preliminary median dose estimates summed over the year 1945--1947 for the primary pathway, air-pasture-cow-milk-thyroid, ranged from low median values of 0.006 rad for upwind adults who obtained milk from backyard cows not on pasture to high median values of 68.0 rad for downwind infants who drank milk from pasture-fed cows. Extremes of the estimated range are a low of essentially zero to upwind adults and a high of almost 3000 rem to downwind infants. 37 refs., 37 figs., 2 tabs.

  11. First report of Legionella pneumophila in car cabin air filters. Are these a potential exposure pathway for professional drivers?

    PubMed

    Alexandropoulou, Ioanna G; Konstantinidis, Theocharis G; Parasidis, Theodoros A; Nikolaidis, Christos; Panopoulou, Maria; Constantinidis, Theodoros C

    2013-12-01

    Recent findings have identified professional drivers as being at an increased risk of Legionnaires' disease. Our hypothesis was that used car cabin air filters represent a reservoir of Legionella bacteria, and thus a potential pathway for contamination. We analysed used cabin air filters from various types of car. The filters were analysed by culture and by molecular methods. Our findings indicated that almost a third of air filters were colonized with Legionella pneumophila. Here, we present the first finding of Legionella spp. in used car cabin air filters. Further investigations are needed in order to confirm this exposure pathway. The presence of Legionella bacteria in used cabin air filters may have been an unknown source of infection until now.

  12. [Analysis of dissemination pathways for poliovirus].

    PubMed

    Ohka, Seii

    2009-06-01

    Poliomyelitis is an acute disease of the central nervous system (CNS) caused by poliovirus (PV). In humans, an infection is initiated by oral ingestion of the virus, followed by multiplication in the alimentary mucosa, from which the virus spreads through the bloodstream. Paralytic poliomyelitis initiates from the invasion of the central nervous system by circulating poliovirus, probably via the blood-brain barrier. After the virus enters the central nervous system, it replicates in neurons, especially in motor neurons, inducing the cell death that causes paralytic poliomyelitis. Along with this route of dissemination, a neuron-specific pathway has been reported in humans, monkeys, and PV-sensitive transgenic (Tg) mice carrying the PV receptor (hPVR/CD155) gene. It is important for the efficient virus dissemination to overcome the barriers as follows; i) to access the target tissue, ii) to enter the cells, iii) to reach the place for the replication, iv) to replicate efficiently. PV is easily transferred to humans orally; however, no rodent model for oral infections has been developed. We analyzed the each barrier above, and showed that PV is inactivated by the low pH of the gastric contents in mice. We also demonstrated that type 1 interferon signaling plays an important role in determining permissivity in the alimentary tract. As for the neural pathway, we demonstrated that direct efficient interaction between the cytoplasmic domain and cytoplasmic dynein is essential for the efficient retrograde transport of PV-containing vesicles along microtubules for the hPVR-dependent PV transport. On the other hand, we found that hPVR-independent axonal transport of PV was also observed in hPVR-Tg and non-Tg mice, indicating that several different pathways for PV axonal transport exist.

  13. Plant Reactome: a resource for plant pathways and comparative analysis

    PubMed Central

    Naithani, Sushma; Preece, Justin; D'Eustachio, Peter; Gupta, Parul; Amarasinghe, Vindhya; Dharmawardhana, Palitha D.; Wu, Guanming; Fabregat, Antonio; Elser, Justin L.; Weiser, Joel; Keays, Maria; Fuentes, Alfonso Munoz-Pomer; Petryszak, Robert; Stein, Lincoln D.; Ware, Doreen; Jaiswal, Pankaj

    2017-01-01

    Plant Reactome (http://plantreactome.gramene.org/) is a free, open-source, curated plant pathway database portal, provided as part of the Gramene project. The database provides intuitive bioinformatics tools for the visualization, analysis and interpretation of pathway knowledge to support genome annotation, genome analysis, modeling, systems biology, basic research and education. Plant Reactome employs the structural framework of a plant cell to show metabolic, transport, genetic, developmental and signaling pathways. We manually curate molecular details of pathways in these domains for reference species Oryza sativa (rice) supported by published literature and annotation of well-characterized genes. Two hundred twenty-two rice pathways, 1025 reactions associated with 1173 proteins, 907 small molecules and 256 literature references have been curated to date. These reference annotations were used to project pathways for 62 model, crop and evolutionarily significant plant species based on gene homology. Database users can search and browse various components of the database, visualize curated baseline expression of pathway-associated genes provided by the Expression Atlas and upload and analyze their Omics datasets. The database also offers data access via Application Programming Interfaces (APIs) and in various standardized pathway formats, such as SBML and BioPAX. PMID:27799469

  14. New Mechanistic Pathways for Criegee-Water Chemistry at the Air/Water Interface.

    PubMed

    Zhu, Chongqin; Kumar, Manoj; Zhong, Jie; Li, Lei; Francisco, Joseph S; Zeng, Xiao Cheng

    2016-09-07

    Understanding Criegee chemistry has become one of central topics in atmospheric research recently. The reaction of Criegee intermediates with gas-phase water clusters has been widely viewed as a key Criegee reaction in the troposphere. However, the effect of aerosols or clouds on Criegee chemistry has received little attention. In this work, we have investigated the reaction between the smallest Criegee intermediate, CH2OO, and water clusters in the gas phase, as well as at the air/water surface using ab initio quantum chemical calculations and adaptive buffered force quantum mechanics/molecular mechanics (QM/MM) dynamics simulations. Our simulation results show that the typical time scale for the reaction of CH2OO with water at the air/water interface is on the order of a few picoseconds, 2-3 orders of magnitude shorter than that in the gas phase. Importantly, the adbf-QM/MM dynamics simulations suggest several reaction pathways for the CH2OO + water reaction at the air/water interface, including the loop-structure-mediated mechanism and the stepwise mechanism. Contrary to the conventional gas-phase CH2OO reaction, the loop-structure is not a prerequisite for the stepwise mechanism. For the latter, a water molecule and the CH2OO at the air/water interface, upon their interaction, can result in the formation of (H3O)(+) and (OH)CH2(OO)(-). Thereafter, a hydrogen bond can be formed between (H3O)(+) and the terminal oxygen atom of (OH)CH2(OO)(-), leading to direct proton transfer and the formation of α-hydroxy methylperoxide, HOCH2OOH. The mechanistic insights obtained from this simulation study should motivate future experimental studies of the effect of water clouds on Criegee chemistry.

  15. Reconstructing networks of pathways via significance analysis of their intersections

    PubMed Central

    Francesconi, Mirko; Remondini, Daniel; Neretti, Nicola; Sedivy, John M; Cooper, Leon N; Verondini, Ettore; Milanesi, Luciano; Castellani, Gastone

    2008-01-01

    Background Significance analysis at single gene level may suffer from the limited number of samples and experimental noise that can severely limit the power of the chosen statistical test. This problem is typically approached by applying post hoc corrections to control the false discovery rate, without taking into account prior biological knowledge. Pathway or gene ontology analysis can provide an alternative way to relax the significance threshold applied to single genes and may lead to a better biological interpretation. Results Here we propose a new analysis method based on the study of networks of pathways. These networks are reconstructed considering both the significance of single pathways (network nodes) and the intersection between them (links). We apply this method for the reconstruction of networks of pathways to two gene expression datasets: the first one obtained from a c-Myc rat fibroblast cell line expressing a conditional Myc-estrogen receptor oncoprotein; the second one obtained from the comparison of Acute Myeloid Leukemia and Acute Lymphoblastic Leukemia derived from bone marrow samples. Conclusion Our method extends statistical models that have been recently adopted for the significance analysis of functional groups of genes to infer links between these groups. We show that groups of genes at the interface between different pathways can be considered as relevant even if the pathways they belong to are not significant by themselves. PMID:18460182

  16. Genome-Wide Pathway Analysis Identifies Genetic Pathways Associated with Psoriasis.

    PubMed

    Aterido, Adrià; Julià, Antonio; Ferrándiz, Carlos; Puig, Lluís; Fonseca, Eduardo; Fernández-López, Emilia; Dauden, Esteban; Sánchez-Carazo, José Luís; López-Estebaranz, José Luís; Moreno-Ramírez, David; Vanaclocha, Francisco; Herrera, Enrique; de la Cueva, Pablo; Dand, Nick; Palau, Núria; Alonso, Arnald; López-Lasanta, María; Tortosa, Raül; García-Montero, Andrés; Codó, Laia; Gelpí, Josep Lluís; Bertranpetit, Jaume; Absher, Devin; Capon, Francesca; Myers, Richard M; Barker, Jonathan N; Marsal, Sara

    2016-03-01

    Psoriasis is a chronic inflammatory disease with a complex genetic architecture. To date, the psoriasis heritability is only partially explained. However, there is increasing evidence that the missing heritability in psoriasis could be explained by multiple genetic variants of low effect size from common genetic pathways. The objective of this study was to identify new genetic variation associated with psoriasis risk at the pathway level. We genotyped 598,258 single nucleotide polymorphisms in a discovery cohort of 2,281 case-control individuals from Spain. We performed a genome-wide pathway analysis using 1,053 reference biological pathways. A total of 14 genetic pathways (PFDR ≤ 2.55 × 10(-2)) were found to be significantly associated with psoriasis risk. Using an independent validation cohort of 7,353 individuals from the UK, a total of 6 genetic pathways were significantly replicated (PFDR ≤ 3.46 × 10(-2)). We found genetic pathways that had not been previously associated with psoriasis risk such as retinol metabolism (Pcombined = 1.84 × 10(-4)), the transport of inorganic ions and amino acids (Pcombined = 1.57 × 10(-7)), and post-translational protein modification (Pcombined = 1.57 × 10(-7)). In the latter pathway, MGAT5 showed a strong network centrality, and its association with psoriasis risk was further validated in an additional case-control cohort of 3,429 individuals (P < 0.05). These findings provide insights into the biological mechanisms associated with psoriasis susceptibility.

  17. Underground air returns as active transportation pathways for radon gas entry into homes.

    PubMed

    Kearfott, K J; Metzger, R L; Holbert, K E

    1992-12-01

    Levels of elevated 222Rn in homes can fail to correlate with measured radium concentrations in soils and surrounding rocks for reasons which can include water sources, building materials, and unusual variations in climate or building construction. Several homes were identified in the Phoenix, AZ metropolitan area with soil radium concentrations of < 0.074 Bq g-1 (2.0 pCi g-1) which had elevated radon concentrations unexplained by geological sources alone. Continuous monitoring of eight houses under different conditions of cooling system usage revealed a definite role of the underground air returns as active transport pathways contributing to the enhancement of the indoor concentration of 222Rn in six of the houses. The ratio of indoor 222Rn concentrations on days when the cooling system was operated continuously compared to days the system was off ranged from essentially one up to a factor exceeding 10.

  18. Steady state analysis of metabolic pathways using Petri nets.

    PubMed

    Voss, Klaus; Heiner, Monika; Koch, Ina

    2003-01-01

    Computer assisted analysis and simulation of biochemical pathways can improve the understanding of the structure and the dynamics of cell processes considerably. The construction and quantitative analysis of kinetic models is often impeded by the lack of reliable data. However, as the topological structure of biochemical systems can be regarded to remain constant in time, a qualitative analysis of a pathway model was shown to be quite promising as it can render a lot of useful knowledge, e. g., about its structural invariants. The topic of this paper are pathways whose substances have reached a dynamic concentration equilibrium (steady state). It is argued that appreciated tools from biochemistry and also low-level Petri nets can yield only part of the desired results, whereas executable high-level net models lead to a number of valuable additional insights by combining symbolic analysis and simulation.

  19. Bioinformatic Approaches to Metabolic Pathways Analysis

    PubMed Central

    Maudsley, Stuart; Chadwick, Wayne; Wang, Liyun; Zhou, Yu; Martin, Bronwen; Park, Sung-Soo

    2015-01-01

    The growth and development in the last decade of accurate and reliable mass data collection techniques has greatly enhanced our comprehension of cell signaling networks and pathways. At the same time however, these technological advances have also increased the difficulty of satisfactorily analyzing and interpreting these ever-expanding datasets. At the present time, multiple diverse scientific communities including molecular biological, genetic, proteomic, bioinformatic, and cell biological, are converging upon a common endpoint, that is, the measurement, interpretation, and potential prediction of signal transduction cascade activity from mass datasets. Our ever increasing appreciation of the complexity of cellular or receptor signaling output and the structural coordination of intracellular signaling cascades has to some extent necessitated the generation of a new branch of informatics that more closely associates functional signaling effects to biological actions and even whole-animal phenotypes. The ability to untangle and hopefully generate theoretical models of signal transduction information flow from transmembrane receptor systems to physiological and pharmacological actions may be one of the greatest advances in cell signaling science. In this overview, we shall attempt to assist the navigation into this new field of cell signaling and highlight several methodologies and technologies to appreciate this exciting new age of signal transduction. PMID:21870222

  20. Bioinformatic approaches to metabolic pathways analysis.

    PubMed

    Maudsley, Stuart; Chadwick, Wayne; Wang, Liyun; Zhou, Yu; Martin, Bronwen; Park, Sung-Soo

    2011-01-01

    The growth and development in the last decade of accurate and reliable mass data collection techniques has greatly enhanced our comprehension of cell signaling networks and pathways. At the same time however, these technological advances have also increased the difficulty of satisfactorily analyzing and interpreting these ever-expanding datasets. At the present time, multiple diverse scientific communities including molecular biological, genetic, proteomic, bioinformatic, and cell biological, are converging upon a common endpoint, that is, the measurement, interpretation, and potential prediction of signal transduction cascade activity from mass datasets. Our ever increasing appreciation of the complexity of cellular or receptor signaling output and the structural coordination of intracellular signaling cascades has to some extent necessitated the generation of a new branch of informatics that more closely associates functional signaling effects to biological actions and even whole-animal phenotypes. The ability to untangle and hopefully generate theoretical models of signal transduction information flow from transmembrane receptor systems to physiological and pharmacological actions may be one of the greatest advances in cell signaling science. In this overview, we shall attempt to assist the navigation into this new field of cell signaling and highlight several methodologies and technologies to appreciate this exciting new age of signal transduction.

  1. Business Case Analysis of the Special Operations Air Mobility Vehicle

    DTIC Science & Technology

    2013-12-01

    NAVAL POSTGRADUATE SCHOOL MONTEREY, CALIFORNIA MBA PROFESSIONAL REPORT BUSINESS CASE ANALYSIS OF THE SPECIAL OPERATIONS AIR...2013 3. REPORT TYPE AND DATES COVERED MBA Professional Report 4. TITLE AND SUBTITLE BUSINESS CASE ANALYSIS OF THE SPECIAL OPERATIONS AIR...perform an industry analysis of the WSC training and aircraft sales industry; and (3) determine the expected government training capabilities and costs

  2. Modeling the air-soil transport pathway of perfluorooctanoic acid in the mid-Ohio Valley using linked air dispersion and vadose zone models

    NASA Astrophysics Data System (ADS)

    Shin, Hyeong-Moo; Ryan, P. Barry; Vieira, Verónica M.; Bartell, Scott M.

    2012-05-01

    As part of an extensive modeling effort on the air-soil-groundwater transport pathway of perfluorooctanoic acid (PFOA), this study was designed to compare the performance of different air dispersion modeling systems (AERMOD vs. ISCST3), and different approaches to handling incomplete meteorological data using a data set with substantial soil measurements and a well characterized point source for air emissions. Two of the most commonly used EPA air dispersion models, AERMOD and ISCST3, were linked with the EPA vadose zone model PRZM-3. Predicted deposition rates from the air dispersion model were used as input values for the vadose zone model to estimate soil concentrations of PFOA at different depths. We applied 34 years of meteorological data including hourly surface measurements from Parkersburg Airport and 5 years of onsite wind direction and speed to the air dispersion models. We compared offsite measured soil concentrations to predictions made for the corresponding sampling depths, focusing on soil rather than air measurements because the offsite soil samples were less likely to be influenced by short-term variability in emission rates and meteorological conditions. PFOA concentrations in surface soil (0-30 cm depth) were under-predicted and those in subsurface soil (>30 cm depth) were over-predicted compared to observed concentrations by both linked air and vadose zone model. Overall, the simulated values from the linked modeling system were positively correlated with those observed in surface soil (Spearman's rho, Rsp = 0.59-0.70) and subsurface soil (Rsp = 0.46-0.48). This approach provides a useful modeling scheme for similar exposure and risk analyses where the air-soil-groundwater transport is a primary contamination pathway.

  3. Asymptotic Analysis of the Wnt/β Signaling Pathway

    NASA Astrophysics Data System (ADS)

    Maris, D. T.; Goussis, D. A.

    2015-01-01

    The Wnt/β-catenin pathway is a signal transduction pathway made of proteins, which plays an important role in oncogenesis. Ethan Lee and and co-workers introduced in 2003 a detailed mathematical model of this pathway, incorporating the kinetics of protein-protein interactions, protein synthesis/degradation and phosphorylation/dephosphorylation. The fast/slow dynamics of Lee's system are examined here, by employing the Computational Singular Perturbation (CSP) algorithm. CSP reproduces the results of the classical singular perturbation analysis in an algorithmic fashion, producing an approximation of (i) the low dimensional Slow Invariant Manifold (SIM), where the solution evolves and (ii) the reduced model that governs the flow there. The temporal variation of the dimensions of the SIM will be presented and the components of the pathway that are responsible (i) for the generation of the SIM and (ii) for driving the system on it will be identified.

  4. Gene network and pathway generation and analysis: Editorial

    SciTech Connect

    Zhao, Zhongming; Sanfilippo, Antonio P.; Huang, Kun

    2011-02-18

    The past decade has witnessed an exponential growth of biological data including genomic sequences, gene annotations, expression and regulation, and protein-protein interactions. A key aim in the post-genome era is to systematically catalogue gene networks and pathways in a dynamic living cell and apply them to study diseases and phenotypes. To promote the research in systems biology and its application to disease studies, we organized a workshop focusing on the reconstruction and analysis of gene networks and pathways in any organisms from high-throughput data collected through techniques such as microarray analysis and RNA-Seq.

  5. Air

    MedlinePlus

    ... do to protect yourself from dirty air . Indoor air pollution and outdoor air pollution Air can be polluted indoors and it can ... this chart to see what things cause indoor air pollution and what things cause outdoor air pollution! Indoor ...

  6. Air Cargo Transportation Route Choice Analysis

    NASA Technical Reports Server (NTRS)

    Obashi, Hiroshi; Kim, Tae-Seung; Oum, Tae Hoon

    2003-01-01

    Using a unique feature of air cargo transshipment data in the Northeast Asian region, this paper identifies the critical factors that determine the transshipment route choice. Taking advantage of the variations in the transport characteristics in each origin-destination airports pair, the paper uses a discrete choice model to describe the transshipping route choice decision made by an agent (i.e., freight forwarder, consolidator, and large shipper). The analysis incorporates two major factors, monetary cost (such as line-haul cost and landing fee) and time cost (i.e., aircraft turnaround time, including loading and unloading time, custom clearance time, and expected scheduled delay), along with other controls. The estimation method considers the presence of unobserved attributes, and corrects for resulting endogeneity by use of appropriate instrumental variables. Estimation results find that transshipment volumes are more sensitive to time cost, and that the reduction in aircraft turnaround time by 1 hour would be worth the increase in airport charges by more than $1000. Simulation exercises measures the impacts of alternative policy scenarios for a Korean airport, which has recently declared their intention to be a future regional hub in the Northeast Asian region. The results suggest that reducing aircraft turnaround time at the airport be an effective strategy, rather than subsidizing to reduce airport charges.

  7. Identification of Pathways for Bipolar Disorder A Meta-analysis

    PubMed Central

    Nurnberger, John I.; Koller, Daniel L.; Jung, Jeesun; Edenberg, Howard J.; Foroud, Tatiana; Guella, Ilaria; Vawter, Marquis P.; Kelsoe, John R.

    2015-01-01

    IMPORTANCE Genome-wide investigations provide systematic information regarding the neurobiology of psychiatric disorders. OBJECTIVE To identify biological pathways that contribute to risk for bipolar disorder (BP) using genes with consistent evidence for association in multiple genome-wide association studies (GWAS). DATA SOURCES Four independent data sets with individual genome-wide data available in July 2011 along with all data sets contributed to the Psychiatric Genomics Consortium Bipolar Group by May 2012. A prior meta-analysis was used as a source for brain gene expression data. STUDY SELECTION The 4 published GWAS were included in the initial sample. All independent BP data sets providing genome-wide data in the Psychiatric Genomics Consortium were included as a replication sample. DATA EXTRACTION AND SYNTHESIS We identified 966 genes that contained 2 or more variants associated with BP at P < .05 in 3 of 4 GWAS data sets (n = 12 127 [5253 cases, 6874 controls]). Simulations using 10 000 replicates of these data sets corrected for gene size and allowed the calculation of an empirical P value for each gene; empirically significant genes were entered into a pathway analysis. Each of these pathways was then tested in the replication sample (n = 8396 [3507 cases, 4889 controls]) using gene set enrichment analysis for single-nucleotide polymorphisms. The 226 genes were also compared with results from a meta-analysis of gene expression in the dorsolateral prefrontal cortex. MAIN OUTCOMES AND MEASURES Empirically significant genes and biological pathways. RESULTS Among 966 genes, 226 were empirically significant (P < .05). Seventeen pathways were overrepresented in analyses of the initial data set. Six of the 17 pathways were associated with BP in both the initial and replication samples: corticotropin-releasing hormone signaling, cardiac β-adrenergic signaling, phospholipase C signaling, glutamate receptor signaling, endothelin 1 signaling, and cardiac

  8. Analysis of Aircraft Evasion Strategies in Air-to-Air Missille Effectiveness Models

    DTIC Science & Technology

    1975-08-01

    AD-A015 238 ANALYSIS OF AIRCRAFT EVASION STRATEGIES IN AIR-TO-AIR MISSILE EFFECTIVENESS MObri ’ G. Carpenter, et al Grumman Aerospace Corporation ...overall tep t Es CIS*atiet d) Oft ’IsNA 1tTNG AC ?v I TV ? corpor te author) 2S. REPORT SECUNITY CLASSIrICA TION Unclassified ;rummn Aerospace... Corporation b RoU N/A I NEPOA’ I ?LE nalysis of Aircraft Evasion Strategies in Air-to-Air Missile Effectiveness Models 4 DESCRIP T IVE *40TS ’Type of repct

  9. Failure-cause analysis: Air preheaters

    NASA Astrophysics Data System (ADS)

    Maloney, K. L.; Benson, R. C.

    1981-07-01

    The major generic equipment and/or operating problems responsible for utility power plant outages are examined. Data analyzed from 118 generating units with an average size over 500 MW and using 236 air heaters demonstrates problems with air preheater systems and their components that contribute to loss in performance and unavailability of generating units. Nine major problem areas are identified: corrosion, fouling, plugging, soot blowers, water wash system, seals, fires, and drive and bearing systems. The indicated causes and effects are discussed. Recommendations are made to improve the reliability of existing air preheaters, and generic problems requiring future research and application of existing technologies are identified.

  10. Pathway analysis of kidney cancer using proteomics and metabolic profiling

    PubMed Central

    Perroud, Bertrand; Lee, Jinoo; Valkova, Nelly; Dhirapong, Amy; Lin, Pei-Yin; Fiehn, Oliver; Kültz, Dietmar; Weiss, Robert H

    2006-01-01

    Background Renal cell carcinoma (RCC) is the sixth leading cause of cancer death and is responsible for 11,000 deaths per year in the US. Approximately one-third of patients present with disease which is already metastatic and for which there is currently no adequate treatment, and no biofluid screening tests exist for RCC. In this study, we have undertaken a comprehensive proteomic analysis and subsequently a pathway and network approach to identify biological processes involved in clear cell RCC (ccRCC). We have used these data to investigate urinary markers of RCC which could be applied to high-risk patients, or to those being followed for recurrence, for early diagnosis and treatment, thereby substantially reducing mortality of this disease. Results Using 2-dimensional electrophoresis and mass spectrometric analysis, we identified 31 proteins which were differentially expressed with a high degree of significance in ccRCC as compared to adjacent non-malignant tissue, and we confirmed some of these by immunoblotting, immunohistochemistry, and comparison to published transcriptomic data. When evaluated by several pathway and biological process analysis programs, these proteins are demonstrated to be involved with a high degree of confidence (p values < 2.0 E-05) in glycolysis, propanoate metabolism, pyruvate metabolism, urea cycle and arginine/proline metabolism, as well as in the non-metabolic p53 and FAS pathways. In a pilot study using random urine samples from both ccRCC and control patients, we performed metabolic profiling and found that only sorbitol, a component of an alternative glycolysis pathway, is significantly elevated at 5.4-fold in RCC patients as compared to controls. Conclusion Extensive pathway and network analysis allowed for the discovery of highly significant pathways from a set of clear cell RCC samples. Knowledge of activation of these processes will lead to novel assays identifying their proteomic and/or metabolomic signatures in biofluids

  11. Analysis of air pollution and greenhouse gases

    SciTech Connect

    Benkovitz, C.M.

    1992-03-01

    The current objective of the project Analysis of Air Pollution and Greenhouse Gases'' is to develop a study of emissions and emission sources that could easily be linked to models of economic activity. Initial studies were conducted to evaluate data currently available linking activity rates and emissions estimates. The emissions inventory developed for the National Acid Precipitation Assessment Program (NAPAP) presents one of the most comprehensive data sets, and was chosen for our initial studies, which are described in this report. Over 99% of the SO{sub 2} emissions, 98% of the NO{sub x} emission and 57% of the VOC emissions from area sources are related to fuel combustion. The majority of emission from these sources are generated by the transportation sector. Activity rates for area sources are not archived with the NAPAP inventory; alternative derivations of these data will be part of the future activities of this project. The availability and completeness of the fuel heat content data in the NAPAP inventory were also studied. Approximately 10% of the SO{sub 2} emissions, 13% of the NO{sub x} emissions and 46% of the VOC emissions are generated by sources with unavailable data for fuel heat content. Initial estimates of pollutant emission rate per unit fuel heat content. Initial estimates of pollutant emission rate per unit fuel heat content were generated. Future studies for this project include the derivation of activity rates for area sources, improved explanations for the default fuel parameters defined in the NAPAP inventory and the development of links to data bases of economic activity.

  12. Pathway analysis of primary central nervous system lymphoma.

    PubMed

    Tun, Han W; Personett, David; Baskerville, Karen A; Menke, David M; Jaeckle, Kurt A; Kreinest, Pamela; Edenfield, Brandy; Zubair, Abba C; O'Neill, Brian P; Lai, Weil R; Park, Peter J; McKinney, Michael

    2008-03-15

    Primary central nervous system (CNS) lymphoma (PCNSL) is a diffuse large B-cell lymphoma (DLBCL) confined to the CNS. A genome-wide gene expression comparison between PCNSL and non-CNS DLBCL was performed, the latter consisting of both nodal and extranodal DLBCL (nDLBCL and enDLBCL), to identify a "CNS signature." Pathway analysis with the program SigPathway revealed that PCNSL is characterized notably by significant differential expression of multiple extracellular matrix (ECM) and adhesion-related pathways. The most significantly up-regulated gene is the ECM-related osteopontin (SPP1). Expression at the protein level of ECM-related SPP1 and CHI3L1 in PCNSL cells was demonstrated by immunohistochemistry. The alterations in gene expression can be interpreted within several biologic contexts with implications for PCNSL, including CNS tropism (ECM and adhesion-related pathways, SPP1, DDR1), B-cell migration (CXCL13, SPP1), activated B-cell subtype (MUM1), lymphoproliferation (SPP1, TCL1A, CHI3L1), aggressive clinical behavior (SPP1, CHI3L1, MUM1), and aggressive metastatic cancer phenotype (SPP1, CHI3L1). The gene expression signature discovered in our study may represent a true "CNS signature" because we contrasted PCNSL with wide-spectrum non-CNS DLBCL on a genomic scale and performed an in-depth bioinformatic analysis.

  13. CRITICAL RADIONUCLIDE AND PATHWAY ANALYSIS FOR THE SAVANNAH RIVER SITE

    SciTech Connect

    Jannik, T.

    2011-08-30

    This report is an update to the analysis, Assessment of SRS Radiological Liquid and Airborne Contaminants and Pathways, that was performed in 1997. An electronic version of this large original report is included in the attached CD to this report. During the operational history (1954 to the present) of the Savannah River Site (SRS), many different radionuclides have been released to the environment from the various production facilities. However, as will be shown by this updated radiological critical contaminant/critical pathway analysis, only a small number of the released radionuclides have been significant contributors to potential doses and risks to offsite people. The analysis covers radiological releases to the atmosphere and to surface waters, the principal media that carry contaminants offsite. These releases potentially result in exposure to offsite people. The groundwater monitoring performed at the site shows that an estimated 5 to 10% of SRS has been contaminated by radionuclides, no evidence exists from the extensive monitoring performed that groundwater contaminated with these constituents has migrated off the site (SRS 2011). Therefore, with the notable exception of radiological source terms originating from shallow surface water migration into site streams, onsite groundwater was not considered as a potential exposure pathway to offsite people. In addition, in response to the Department of Energy's (DOE) Order 435.1, several Performance Assessments (WSRC 2008; LWO 2009; SRR 2010; SRR 2011) and a Comprehensive SRS Composite Analysis (SRNO 2010) have recently been completed at SRS. The critical radionuclides and pathways identified in these extensive reports are discussed and, where applicable, included in this analysis.

  14. Assessment of health benefits related to air quality improvement strategies in urban areas: An Impact Pathway Approach.

    PubMed

    Silveira, Carlos; Roebeling, Peter; Lopes, Myriam; Ferreira, Joana; Costa, Solange; Teixeira, João P; Borrego, Carlos; Miranda, Ana I

    2016-12-01

    Air pollution is, increasingly, a concern to our society given the threats to human health and the environment. Concerted actions to improve air quality have been taken at different levels, such as through the development of Air Quality Plans (AQPs). However, air quality impacts associated with the implementation of abatement measures included in AQPs are often neglected. In order to identify the major gaps and strengths in current knowledge, a literature review has been performed on existing methodologies to estimate air pollution-related health impacts and subsequent external costs. Based on this review, the Impact Pathway Approach was adopted and applied within the context of the MAPLIA research project to assess the health impacts and benefits (or avoided external costs) derived from improvements in air quality. Seven emission abatement scenarios, based on individual and combined abatement measures, were tested for the major activity sectors (traffic, residential and industrial combustion and production processes) of a Portuguese urban area (Grande Porto) with severe particular matter (PM10) air pollution problems. Results revealed a strong positive correlation between population density and health benefits obtained from the assessed reduction scenarios. As a consequence, potential health benefits from reduction scenarios are largest in densely populated areas with high anthropic activity and, thus, where air pollution problems are most alarming. Implementation of all measures resulted in a reduction in PM10 emissions by almost 8%, improving air quality by about 1% and contributing to a benefit of 8.8 million €/year for the entire study domain. The introduction of PM10 reduction technologies in industrial units was the most beneficial abatement measure. This study intends to contribute to policy support for decision-making on air quality management.

  15. AOP: An R Package For Sufficient Causal Analysis in Pathway ...

    EPA Pesticide Factsheets

    Summary: How can I quickly find the key events in a pathway that I need to monitor to predict that a/an beneficial/adverse event/outcome will occur? This is a key question when using signaling pathways for drug/chemical screening in pharma-cology, toxicology and risk assessment. By identifying these sufficient causal key events, we have fewer events to monitor for a pathway, thereby decreasing assay costs and time, while maximizing the value of the information. I have developed the “aop” package which uses backdoor analysis of causal net-works to identify these minimal sets of key events that are suf-ficient for making causal predictions. Availability and Implementation: The source and binary are available online through the Bioconductor project (http://www.bioconductor.org/) as an R package titled “aop”. The R/Bioconductor package runs within the R statistical envi-ronment. The package has functions that can take pathways (as directed graphs) formatted as a Cytoscape JSON file as input, or pathways can be represented as directed graphs us-ing the R/Bioconductor “graph” package. The “aop” package has functions that can perform backdoor analysis to identify the minimal set of key events for making causal predictions.Contact: burgoon.lyle@epa.gov This paper describes an R/Bioconductor package that was developed to facilitate the identification of key events within an AOP that are the minimal set of sufficient key events that need to be tested/monit

  16. Altered Pathway Analyzer: A gene expression dataset analysis tool for identification and prioritization of differentially regulated and network rewired pathways

    PubMed Central

    Kaushik, Abhinav; Ali, Shakir; Gupta, Dinesh

    2017-01-01

    Gene connection rewiring is an essential feature of gene network dynamics. Apart from its normal functional role, it may also lead to dysregulated functional states by disturbing pathway homeostasis. Very few computational tools measure rewiring within gene co-expression and its corresponding regulatory networks in order to identify and prioritize altered pathways which may or may not be differentially regulated. We have developed Altered Pathway Analyzer (APA), a microarray dataset analysis tool for identification and prioritization of altered pathways, including those which are differentially regulated by TFs, by quantifying rewired sub-network topology. Moreover, APA also helps in re-prioritization of APA shortlisted altered pathways enriched with context-specific genes. We performed APA analysis of simulated datasets and p53 status NCI-60 cell line microarray data to demonstrate potential of APA for identification of several case-specific altered pathways. APA analysis reveals several altered pathways not detected by other tools evaluated by us. APA analysis of unrelated prostate cancer datasets identifies sample-specific as well as conserved altered biological processes, mainly associated with lipid metabolism, cellular differentiation and proliferation. APA is designed as a cross platform tool which may be transparently customized to perform pathway analysis in different gene expression datasets. APA is freely available at http://bioinfo.icgeb.res.in/APA. PMID:28084397

  17. Biannual cycles of organochlorine pesticide enantiomers in arctic air suggest changing sources and pathways

    NASA Astrophysics Data System (ADS)

    Bidleman, T. F.; Jantunen, L. M.; Hung, H.; Ma, J.; Stern, G. A.; Rosenberg, B.; Racine, J.

    2014-09-01

    Air samples collected during 1994-2000 at the Canadian arctic air monitoring station Alert (82°30' N, 62°20' W) were analyzed by enantiospecific gas chromatography - mass spectrometry for α-hexachlorocyclohexane (α-HCH), trans-chlordane (TC) and cis-chlordane (CC). Results were expressed as enantiomer fractions (EF = quantities of (+)/[(+) + (-)] enantiomers), where EFs = 0.5, <0.5 and >0.5 indicate racemic composition, and preferential depletion of (+) and (-) enantiomers, respectively. Long-term average EFs were close to racemic values for α-HCH (0.504 ± 0.004, n = 197) and CC (0.505 ± 0.004, n = 162), and deviated farther from racemic for TC (0.470 ± 0.013, n = 165). Digital filtration analysis revealed biannual cycles of lower α-HCH EFs in summer-fall and higher EFs in winter-spring. These cycles suggest volatilization of partially degraded α-HCH with EF < 0.5 from open water and advection to Alert during the warm season, and background transport of α-HCH with EF > 0.5 during the cold season. The contribution of sea-volatilized α-HCH was only 11% at Alert, vs. 32% at Resolute Bay (74.68° N, 94.90° W) in 1999. EFs of TC also followed biannual cycles of lower and higher values in the warm and cold seasons. These were in phase with low and high cycles of the TC/CC ratio (expressed as FTC = TC/(TC + CC)), which suggests greater contribution of microbially "weathered" TC in summer-fall vs. winter-spring. CC was closer to racemic than TC and displayed seasonal cycles only in 1997-1998. EF profiles are likely to change with rising contribution of secondary emission sources, weathering of residues in the environment, and loss of ice cover in the Arctic. Enantiomer-specific analysis could provide added forensic capability to air monitoring programs.

  18. Annual cycles of organochlorine pesticide enantiomers in Arctic air suggest changing sources and pathways

    NASA Astrophysics Data System (ADS)

    Bidleman, T. F.; Jantunen, L. M.; Hung, H.; Ma, J.; Stern, G. A.; Rosenberg, B.; Racine, J.

    2015-02-01

    Air samples collected during 1994-2000 at the Canadian Arctic air monitoring station Alert (82°30' N, 62°20' W) were analysed by enantiospecific gas chromatography-mass spectrometry for α-hexachlorocyclohexane (α-HCH), trans-chlordane (TC) and cis-chlordane (CC). Results were expressed as enantiomer fractions (EF = peak areas of (+)/[(+) + (-)] enantiomers), where EFs = 0.5, < 0.5 and > 0.5 indicate racemic composition, and preferential depletion of (+) and (-) enantiomers, respectively. Long-term average EFs were close to racemic values for α -HCH (0.504 ± 0.004, n = 197) and CC (0.505 ± 0.004, n = 162), and deviated farther from racemic for TC (0.470 ± 0.013, n = 165). Digital filtration analysis revealed annual cycles of lower α-HCH EFs in summer-fall and higher EFs in winter-spring. These cycles suggest volatilization of partially degraded α-HCH with EF < 0.5 from open water and advection to Alert during the warm season, and background transport of α-HCH with EF > 0.5 during the cold season. The contribution of sea-volatilized α-HCH was only 11% at Alert, vs. 32% at Resolute Bay (74.68° N, 94.90° W) in 1999. EFs of TC also followed annual cycles of lower and higher values in the warm and cold seasons. These were in phase with low and high cycles of the TC/CC ratio (expressed as FTC = TC/(TC+CC)), which suggests greater contribution of microbially "weathered" TC in summer-fall versus winter-spring. CC was closer to racemic than TC and displayed seasonal cycles only in 1997-1998. EF profiles are likely to change with rising contribution of secondary emission sources, weathering of residues in the environment, and loss of ice cover in the Arctic. Enantiomer-specific analysis could provide added forensic capability to air monitoring programs.

  19. BMEWS Capture and Analysis of Reflected Energy Clear Air ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    BMEWS Capture and Analysis of Reflected Energy - Clear Air Force Station, Ballistic Missile Early Warning System Site II, One mile west of mile marker 293.5 on Parks Highway, 5 miles southwest of Anderson, Anderson, Denali Borough, AK

  20. Personalised pathway analysis reveals association between DNA repair pathway dysregulation and chromosomal instability in sporadic breast cancer.

    PubMed

    Liu, Chao; Srihari, Sriganesh; Lal, Samir; Gautier, Benoît; Simpson, Peter T; Khanna, Kum Kum; Ragan, Mark A; Lê Cao, Kim-Anh

    2016-01-01

    The Homologous Recombination (HR) pathway is crucial for the repair of DNA double-strand breaks (DSBs) generated during DNA replication. Defects in HR repair have been linked to the initiation and development of a wide variety of human malignancies, and exploited in chemical, radiological and targeted therapies. In this study, we performed a personalised pathway analysis independently for four large sporadic breast cancer cohorts to investigate the status of HR pathway dysregulation in individual sporadic breast tumours, its association with HR repair deficiency and its impact on tumour characteristics. Specifically, we first manually curated a list of HR genes according to our recent review on this pathway (Liu et al., 2014), and then applied a personalised pathway analysis method named Pathifier (Drier et al., 2013) on the expression levels of the curated genes to obtain an HR score quantifying HR pathway dysregulation in individual tumours. Based on the score, we observed a great diversity in HR dysregulation between and within gene expression-based breast cancer subtypes, and by using two published HR-defect signatures, we found HR pathway dysregulation reflects HR repair deficiency. Furthermore, we identified a novel association between HR pathway dysregulation and chromosomal instability (CIN) in sporadic breast cancer. Although CIN has long been considered as a hallmark of most solid tumours, with recent extensive studies highlighting its importance in tumour evolution and drug resistance, the molecular basis of CIN in sporadic cancers remains poorly understood. Our results imply that HR pathway dysregulation might contribute to CIN in sporadic breast cancer.

  1. pathDIP: an annotated resource for known and predicted human gene-pathway associations and pathway enrichment analysis

    PubMed Central

    Rahmati, Sara; Abovsky, Mark; Pastrello, Chiara; Jurisica, Igor

    2017-01-01

    Molecular pathway data are essential in current computational and systems biology research. While there are many primary and integrated pathway databases, several challenges remain, including low proteome coverage (57%), low overlap across different databases, unavailability of direct information about underlying physical connectivity of pathway members, and high fraction of protein-coding genes without any pathway annotations, i.e. ‘pathway orphans’. In order to address all these challenges, we developed pathDIP, which integrates data from 20 source pathway databases, ‘core pathways’, with physical protein–protein interactions to predict biologically relevant protein–pathway associations, referred to as ‘extended pathways’. Cross-validation determined 71% recovery rate of our predictions. Data integration and predictions increase coverage of pathway annotations for protein-coding genes to 86%, and provide novel annotations for 5732 pathway orphans. PathDIP (http://ophid.utoronto.ca/pathdip) annotates 17 070 protein-coding genes with 4678 pathways, and provides multiple query, analysis and output options. PMID:27899558

  2. Task analysis of Air Force pharmacy practice.

    PubMed

    Bartholomew, A; Sawyer, W T; Coats, L

    1995-01-15

    The frequency with which United States Air Force pharmacists perform specific professional tasks and the pharmacists' views as to the importance of those tasks were studied. A questionnaire was prepared that asked recipients to rate each of 36 tasks selected as representing the spectrum of practice activities. There were four categories of tasks: managerial tasks, dispensing tasks, drug information tasks, and patient care tasks. Recipients rated the tasks with respect to frequency of performance and importance on separate 6-point scales. The questionnaire was mailed in May 1991 to the 225 pharmacists then serving in the Air Force worldwide. Of the 225 questionnaires, 150 usable questionnaires were returned (response rate, 67%). All the tasks in the survey were performed by at least one Air Force pharmacy officer, although the frequency of task performance varied. In particular, the frequency of many patient care tasks was low. All the tasks were perceived to have some importance, but drug information tasks were rated as being significantly more important than tasks in the other categories; patient care tasks were rated lowest in importance. The results varied with the respondents' demographic characteristics. Pharmacy officers with more years of service, more senior positions, higher rank, or an advanced degree in a field other than pharmacy tended to give responses that diverged from those of the population. A 1991 survey showed an awareness among Air Force pharmacists of the need to orient practice around patient care; however, they were not spending substantial time on patient care and tended to view it as less important than more traditional pharmacy tasks.

  3. Parameters used in the environmental pathways and radiological dose modules of the Phase I air pathway code

    SciTech Connect

    Shindle, S.F.; Ikenberry, T.A.; Napier, B.A.

    1992-05-01

    This report is a description of work performed for the Hanford Environmental Dose Reconstruction (HEDR) Project. The HEDR Project was established to estimate radiation doses to individuals resulting from releases of radionuclides from the Hanford Site since 1944, when facilities there first began operating. An independent Technical Steering Panel directs the project, which is conducted by Battelle staff from the Pacific Northwest Laboratory. The objective of Phase 1 of the HEDR Project was to demonstrate through calculation that adequate models and support data existed or could be developed to allow estimation of realistic doses to individuals from historical Hanford Site radionuclide releases. The HEDR Phase 1 computer code was used to model the transport of iodine-131 released to the atmosphere from the Hanford Site facilities, through environmental pathways to points of human exposure. Output from the code was preliminary estimates of doses received by members of the public living in the vicinity of the Hanford Site. Later project work continues to build upon Phase 1 progress in order to refine dose estimates.

  4. Analysis of PTCH/SMO/SHH pathway genes in medulloblastoma.

    PubMed

    Zurawel, R H; Allen, C; Chiappa, S; Cato, W; Biegel, J; Cogen, P; de Sauvage, F; Raffel, C

    2000-01-01

    Inactivation of the PTCH tumor suppressor gene occurs in a subset of sporadic medulloblastomas, suggesting that alterations in the PTCH pathway may be important in the development of this tumor. In order to address the frequency of genetic alterations affecting genes in this pathway, we used a combination of loss of heterozygosity (LOH) analysis, single-stranded conformational polymorphism (SSCP) analysis, and direct sequencing of DNA samples from sporadic primitive neuroectodermal tumors (PNETs). To identify alterations in the PTCH gene, we performed LOH analysis on 37 tumor DNA samples. Of those with matched constitutional DNA samples, one demonstrated LOH. Of those without matched constitutional DNA, six were homozygous with all markers. All exons of the PTCH gene were sequenced in these seven tumors, and three mutations were found. To identify alterations in the SHH and SMO genes, we analyzed all exons of both genes in 24 tumors with SSCP and sequenced any exons that showed aberrant band patterns. No mutations were found in either SHH or SMO in any tumor. We also identified the following genes as candidate tumor suppressors based on their roles in controlling hh/ptc signaling in Drosophila: EN-1 and EN-2, deletion of which results in a lack of cerebellar development in mice; SMAD family members 1-7, and protein kinase A subunits RIalpha, RIbeta, RIIbeta, Calpha, and Cbeta. Each of these genes was investigated in a panel of 24 matched constitutional and tumor DNA samples. Our search revealed no mutations in any of these genes. Thus, PTCH is the only gene in this complex pathway that is mutated with notable frequency in PNET. Genes Chromosomes Cancer 27:44-51, 2000.

  5. Air-to-air combat analysis - Review of differential-gaming approaches

    NASA Technical Reports Server (NTRS)

    Ardema, M. D.

    1981-01-01

    The problem of evaluating the combat performance of fighter/attack aircraft is discussed, and the mathematical nature of the problem is examined. The following approaches to air combat analysis are reviewed: (1) differential-turning differential game and (2) coplanar differential game. Selected numerical examples of these approaches are presented. The relative advantages and disadvantages of each are analyzed, and it is concluded that air combat analysis is an extremely difficult mathematical problem and that no one method of approach is best for all purposes. The paper concludes with a discussion of how the two approaches might be used in a complementary manner.

  6. Penalized differential pathway analysis of integrative oncogenomics studies.

    PubMed

    van Wieringen, Wessel N; van de Wiel, Mark A

    2014-04-01

    Through integration of genomic data from multiple sources, we may obtain a more accurate and complete picture of the molecular mechanisms underlying tumorigenesis. We discuss the integration of DNA copy number and mRNA gene expression data from an observational integrative genomics study involving cancer patients. The two molecular levels involved are linked through the central dogma of molecular biology. DNA copy number aberrations abound in the cancer cell. Here we investigate how these aberrations affect gene expression levels within a pathway using observational integrative genomics data of cancer patients. In particular, we aim to identify differential edges between regulatory networks of two groups involving these molecular levels. Motivated by the rate equations, the regulatory mechanism between DNA copy number aberrations and gene expression levels within a pathway is modeled by a simultaneous-equations model, for the one- and two-group case. The latter facilitates the identification of differential interactions between the two groups. Model parameters are estimated by penalized least squares using the lasso (L1) penalty to obtain a sparse pathway topology. Simulations show that the inclusion of DNA copy number data benefits the discovery of gene-gene interactions. In addition, the simulations reveal that cis-effects tend to be over-estimated in a univariate (single gene) analysis. In the application to real data from integrative oncogenomic studies we show that inclusion of prior information on the regulatory network architecture benefits the reproducibility of all edges. Furthermore, analyses of the TP53 and TGFb signaling pathways between ER+ and ER- samples from an integrative genomics breast cancer study identify reproducible differential regulatory patterns that corroborate with existing literature.

  7. Pathway analysis of bladder cancer genome-wide association study identifies novel pathways involved in bladder cancer development

    PubMed Central

    Chen, Meng; Rothman, Nathaniel; Ye, Yuanqing; Gu, Jian; Scheet, Paul A.; Huang, Maosheng; Chang, David W.; Dinney, Colin P.; Silverman, Debra T.; Figueroa, Jonine D.; Chanock, Stephen J.; Wu, Xifeng

    2016-01-01

    Genome-wide association studies (GWAS) are designed to identify individual regions associated with cancer risk, but only explain a small fraction of the inherited variability. Alternative approach analyzing genetic variants within biological pathways has been proposed to discover networks of susceptibility genes with additional effects. The gene set enrichment analysis (GSEA) may complement and expand traditional GWAS analysis to identify novel genes and pathways associated with bladder cancer risk. We selected three GSEA methods: Gen-Gen, Aligator, and the SNP Ratio Test to evaluate cellular signaling pathways involved in bladder cancer susceptibility in a Texas GWAS population. The candidate genetic polymorphisms from the significant pathway selected by GSEA were validated in an independent NCI GWAS. We identified 18 novel pathways (P < 0.05) significantly associated with bladder cancer risk. Five of the most promising pathways (P ≤ 0.001 in any of the three GSEA methods) among the 18 pathways included two cell cycle pathways and neural cell adhesion molecule (NCAM), platelet-derived growth factor (PDGF), and unfolded protein response pathways. We validated the candidate polymorphisms in the NCI GWAS and found variants of RAPGEF1, SKP1, HERPUD1, CACNB2, CACNA1C, CACNA1S, COL4A2, SRC, and CACNA1C were associated with bladder cancer risk. Two CCNE1 variants, rs8102137 and rs997669, from cell cycle pathways showed the strongest associations; the CCNE1 signal at 19q12 has already been reported in previous GWAS. These findings offer additional etiologic insights highlighting the specific genes and pathways associated with bladder cancer development. GSEA may be a complementary tool to GWAS to identify additional loci of cancer susceptibility. PMID:27738493

  8. Indoor air quality analysis based on Hadoop

    NASA Astrophysics Data System (ADS)

    Tuo, Wang; Yunhua, Sun; Song, Tian; Liang, Yu; Weihong, Cui

    2014-03-01

    The air of the office environment is our research object. The data of temperature, humidity, concentrations of carbon dioxide, carbon monoxide and ammonia are collected peer one to eight seconds by the sensor monitoring system. And all the data are stored in the Hbase database of Hadoop platform. With the help of HBase feature of column-oriented store and versioned (automatically add the time column), the time-series data sets are bulit based on the primary key Row-key and timestamp. The parallel computing programming model MapReduce is used to process millions of data collected by sensors. By analysing the changing trend of parameters' value at different time of the same day and at the same time of various dates, the impact of human factor and other factors on the room microenvironment is achieved according to the liquidity of the office staff. Moreover, the effective way to improve indoor air quality is proposed in the end of this paper.

  9. Comparative expression pathway analysis of human and canine mammary tumors

    PubMed Central

    Uva, Paolo; Aurisicchio, Luigi; Watters, James; Loboda, Andrey; Kulkarni, Amit; Castle, John; Palombo, Fabio; Viti, Valentina; Mesiti, Giuseppe; Zappulli, Valentina; Marconato, Laura; Abramo, Francesca; Ciliberto, Gennaro; Lahm, Armin; La Monica, Nicola; de Rinaldis, Emanuele

    2009-01-01

    Background Spontaneous tumors in dog have been demonstrated to share many features with their human counterparts, including relevant molecular targets, histological appearance, genetics, biological behavior and response to conventional treatments. Mammary tumors in dog therefore provide an attractive alternative to more classical mouse models, such as transgenics or xenografts, where the tumour is artificially induced. To assess the extent to which dog tumors represent clinically significant human phenotypes, we performed the first genome-wide comparative analysis of transcriptional changes occurring in mammary tumors of the two species, with particular focus on the molecular pathways involved. Results We analyzed human and dog gene expression data derived from both tumor and normal mammary samples. By analyzing the expression levels of about ten thousand dog/human orthologous genes we observed a significant overlap of genes deregulated in the mammary tumor samples, as compared to their normal counterparts. Pathway analysis of gene expression data revealed a great degree of similarity in the perturbation of many cancer-related pathways, including the 'PI3K/AKT', 'KRAS', 'PTEN', 'WNT-beta catenin' and 'MAPK cascade'. Moreover, we show that the transcriptional relationships between different gene signatures observed in human breast cancer are largely maintained in the canine model, suggesting a close interspecies similarity in the network of cancer signalling circuitries. Conclusion Our data confirm and further strengthen the value of the canine mammary cancer model and open up new perspectives for the evaluation of novel cancer therapeutics and the development of prognostic and diagnostic biomarkers to be used in clinical studies. PMID:19327144

  10. The xeroderma pigmentosum pathway: decision tree analysis of DNA quality.

    PubMed

    Naegeli, Hanspeter; Sugasawa, Kaoru

    2011-07-15

    The nucleotide excision repair (NER) system is a fundamental cellular stress response that uses only a handful of DNA binding factors, mutated in the cancer-prone syndrome xeroderma pigmentosum (XP), to detect an astounding diversity of bulky base lesions, including those induced by ultraviolet light, electrophilic chemicals, oxygen radicals and further genetic insults. Several of these XP proteins are characterized by a mediocre preference for damaged substrates over the native double helix but, intriguingly, none of them recognizes injured bases with sufficient selectivity to account for the very high precision of bulky lesion excision. Instead, substrate versatility as well as damage specificity and strand selectivity are achieved by a multistage quality control strategy whereby different subunits of the XP pathway, in succession, interrogate the DNA double helix for a distinct abnormality in its structural or dynamic parameters. Through this step-by-step filtering procedure, the XP proteins operate like a systematic decision making tool, generally known as decision tree analysis, to sort out rare damaged bases embedded in a vast excess of native DNA. The present review is focused on the mechanisms by which multiple XP subunits of the NER pathway contribute to the proposed decision tree analysis of DNA quality in eukaryotic cells.

  11. Investigating ego modules and pathways in osteosarcoma by integrating the EgoNet algorithm and pathway analysis

    PubMed Central

    Chen, X.Y.; Chen, Y.H.; Zhang, L.J.; Wang, Y.; Tong, Z.C.

    2017-01-01

    Osteosarcoma (OS) is the most common primary bone malignancy, but current therapies are far from effective for all patients. A better understanding of the pathological mechanism of OS may help to achieve new treatments for this tumor. Hence, the objective of this study was to investigate ego modules and pathways in OS utilizing EgoNet algorithm and pathway-related analysis, and reveal pathological mechanisms underlying OS. The EgoNet algorithm comprises four steps: constructing background protein-protein interaction (PPI) network (PPIN) based on gene expression data and PPI data; extracting differential expression network (DEN) from the background PPIN; identifying ego genes according to topological features of genes in reweighted DEN; and collecting ego modules using module search by ego gene expansion. Consequently, we obtained 5 ego modules (Modules 2, 3, 4, 5, and 6) in total. After applying the permutation test, all presented statistical significance between OS and normal controls. Finally, pathway enrichment analysis combined with Reactome pathway database was performed to investigate pathways, and Fisher's exact test was conducted to capture ego pathways for OS. The ego pathway for Module 2 was CLEC7A/inflammasome pathway, while for Module 3 a tetrasaccharide linker sequence was required for glycosaminoglycan (GAG) synthesis, and for Module 6 was the Rho GTPase cycle. Interestingly, genes in Modules 4 and 5 were enriched in the same pathway, the 2-LTR circle formation. In conclusion, the ego modules and pathways might be potential biomarkers for OS therapeutic index, and give great insight of the molecular mechanism underlying this tumor. PMID:28225867

  12. Investigating ego modules and pathways in osteosarcoma by integrating the EgoNet algorithm and pathway analysis.

    PubMed

    Chen, X Y; Chen, Y H; Zhang, L J; Wang, Y; Tong, Z C

    2017-02-16

    Osteosarcoma (OS) is the most common primary bone malignancy, but current therapies are far from effective for all patients. A better understanding of the pathological mechanism of OS may help to achieve new treatments for this tumor. Hence, the objective of this study was to investigate ego modules and pathways in OS utilizing EgoNet algorithm and pathway-related analysis, and reveal pathological mechanisms underlying OS. The EgoNet algorithm comprises four steps: constructing background protein-protein interaction (PPI) network (PPIN) based on gene expression data and PPI data; extracting differential expression network (DEN) from the background PPIN; identifying ego genes according to topological features of genes in reweighted DEN; and collecting ego modules using module search by ego gene expansion. Consequently, we obtained 5 ego modules (Modules 2, 3, 4, 5, and 6) in total. After applying the permutation test, all presented statistical significance between OS and normal controls. Finally, pathway enrichment analysis combined with Reactome pathway database was performed to investigate pathways, and Fisher's exact test was conducted to capture ego pathways for OS. The ego pathway for Module 2 was CLEC7A/inflammasome pathway, while for Module 3 a tetrasaccharide linker sequence was required for glycosaminoglycan (GAG) synthesis, and for Module 6 was the Rho GTPase cycle. Interestingly, genes in Modules 4 and 5 were enriched in the same pathway, the 2-LTR circle formation. In conclusion, the ego modules and pathways might be potential biomarkers for OS therapeutic index, and give great insight of the molecular mechanism underlying this tumor.

  13. Analysis of membrane lipid biogenesis pathways using yeast genetics.

    PubMed

    Gsell, Martina; Daum, Günther

    2013-01-01

    The yeast Saccharomyces cerevisiae has become a valuable eukaryotic model organism to study biochemical and cellular processes at a molecular basis. A common strategy for such studies is the use of single and multiple mutants constructed by genetic manipulation which are compromised in individual enzymatic steps or certain metabolic pathways. Here, we describe selected examples of yeast research on phospholipid metabolism with emphasis on our own work dealing with investigations of phosphatidylethanolamine synthesis. Such studies start with the selection and construction of appropriate mutants and lead to phenotype analysis, lipid profiling, enzymatic analysis, and in vivo experiments. Comparing results obtained with wild-type and mutant strains allows us to understand the role of gene products and metabolic processes in more detail. Such studies are valuable not only for contributing to our knowledge of the complex network of lipid metabolism, but also of effects of lipids on structure and function of cellular membranes.

  14. Combining pathway analysis with flux balance analysis for the comprehensive study of metabolic systems.

    PubMed

    Schilling, C H; Edwards, J S; Letscher, D; Palsson, B Ø

    The elucidation of organism-scale metabolic networks necessitates the development of integrative methods to analyze and interpret the systemic properties of cellular metabolism. A shift in emphasis from single metabolic reactions to systemically defined pathways is one consequence of such an integrative analysis of metabolic systems. The constraints of systemic stoichiometry, and limited thermodynamics have led to the definition of the flux space within the context of convex analysis. The flux space of the metabolic system, containing all allowable flux distributions, is constrained to a convex polyhedral cone in a high-dimensional space. From metabolic pathway analysis, the edges of the high-dimensional flux cone are vectors that correspond to systemically defined "extreme pathways" spanning the capabilities of the system. The addition of maximum flux capacities of individual metabolic reactions serves to further constrain the flux space and has led to the development of flux balance analysis using linear optimization to calculate optimal flux distributions. Here we provide the precise theoretical connections between pathway analysis and flux balance analysis allowing for their combined application to study integrated metabolic function. Shifts in metabolic behavior are calculated using linear optimization and are then interpreted using the extreme pathways to demonstrate the concept of pathway utilization. Changes to the reaction network, such as the removal of a reaction, can lead to the generation of suboptimal phenotypes that can be directly attributed to the loss of pathway function and capabilities. Optimal growth phenotypes are calculated as a function of environmental variables, such as the availability of substrate and oxygen, leading to the definition of phenotypic phase planes. It is illustrated how optimality properties of the computed flux distributions can be interpreted in terms of the extreme pathways. Together these developments are applied to an

  15. Air pollution and venous thrombosis: a meta-analysis

    PubMed Central

    Tang, Liang; Wang, Qing-Yun; Cheng, Zhi-Peng; Hu, Bei; Liu, Jing-Di; Hu, Yu

    2016-01-01

    Exposure to air pollution has been linked to cardiovascular and respiratory disorders. However, the effect of air pollution on venous thrombotic disorders is uncertain. We performed a meta-analysis to assess the association between air pollution and venous thrombosis. PubMed, Embase, EBM Reviews, Healthstar, Global Health, Nursing Database, and Web of Science were searched for citations on air pollutants (carbon monoxide, sulfur dioxide, nitrogen dioxide, ozone, and particulate matters) and venous thrombosis. Using a random-effects model, overall risk estimates were derived for each increment of 10 μg/m3 of pollutant concentration. Of the 485 in-depth reviewed studies, 8 citations, involving approximately 700,000 events, fulfilled the inclusion criteria. All the main air pollutants analyzed were not associated with an increased risk of venous thrombosis (OR = 1.005, 95% CI = 0.998–1.012 for PM2.5; OR = 0.995, 95% CI = 0.984–1.007 for PM10; OR = 1.006, 95% CI = 0.994–1.019 for NO2). Based on exposure period and thrombosis location, additional subgroup analyses provided results comparable with those of the overall analyses. There was no evidence of publication bias. Therefore, this meta analysis does not suggest the possible role of air pollution as risk factor for venous thrombosis in general population. PMID:27600652

  16. Thermodynamic analysis and optimization of air-cooled heat exchangers

    NASA Astrophysics Data System (ADS)

    Salimpour, Mohammad Reza; Bahrami, Zabihollah

    2011-01-01

    In the present study, a thermodynamic second-law analysis was performed to investigate the effects of different geometry and flow parameters on the air-cooled heat exchanger performance. For this purpose, the entropy generation due to heat transfer and pressure loss of internal and external flows of the air-cooled heat exchanger was calculated; and it was observed that the total entropy generation has a minimum at special tube-side Reynolds number. Also, it was seen that the increasing of the tube-side Reynolds number resulted in the rise of the irreversibility of the air-cooled heat exchanger. The results also showed when air-side Reynolds number decreased, the entropy generation rate of the external flow reduced. Finally, based on the computed results, a new correlation was developed to predict the optimum Reynolds number of the tube-side fluid flow.

  17. A review of risk analysis and helicopter air ambulance accidents.

    PubMed

    Nix, Sam; Buckner, Steven; Cercone, Richard

    2014-01-01

    The Federal Aviation Administration announced a final rule in February 2014 that includes a requirement for helicopter air ambulance operators to institute preflight risk analysis programs. This qualitative study examined risk factors that were described in 22 preliminary, factual, and probable cause helicopter air ambulance accident and incident reports that were initiated by the National Transportation Safety Board between January 1, 2011, and December 31, 2013. Insights into the effectiveness of existing preflight risk analysis strategies were gained by comparing these risk factors with the preflight risk analysis guidance that is published by the Federal Aviation Administration in the Flight Standards Information Management System. When appropriate, a deeper understanding of the human factors that may have contributed to occurrences was gained through methodologies that are described in the Human Factors Analysis and Classification System. The results of this study suggest that there are some vulnerabilities in existing preflight risk analysis guidelines that may affect safety in the helicopter air ambulance industry. The likelihood that human factors contributed to most of the helicopter air ambulance accidents and incidents that occurred during the study period was also evidenced. The results of this study suggest that effective risk analysis programs should provide pilots with both preflight and in-flight resources.

  18. Quantifying a pathway: kinetic analysis of actin dendritic nucleation.

    PubMed

    Kraikivski, Pavel; Slepchenko, Boris M

    2010-08-04

    Progress in uncovering the reaction networks that underlie important cell functions is laying the groundwork for quantitative identification of protein-interaction pathways. Since direct measurement of rate constants is not always feasible, the parameters are often inferred from multiple pieces of data using kinetic analyses based on appropriate mathematical models. The success of this approach relies on the sufficiency of available experimental data for a unique parameterization of the network. The concept of a rate-limiting step is applied to the analysis of experimental data that are usually used to quantify a pathway of actin dendritic nucleation, the Arp2/3-mediated mechanism that enables rapid changes of cell shape in response to external cues. The method yields analytical descriptions of the dynamics of polymerized actin and provides insights into how the experimental curves should be analyzed. It is shown that dynamics measured by pyrene-labeled actin assays with varying Arp2/3 concentrations are equally well described by two different rate-limiting steps: 1), binding of a nucleating complex to the side of a preexisting filament; or 2), its subsequent activation. To distinguish between the alternatives, we propose experiments with varying concentrations of actin monomers, taking advantage of the fact that the number of branches in the two cases depends differently on the initial monomer concentration. The idea is tested by simulating the proposed experiments with the use of spatial stochastic modeling.

  19. Integrated analysis of hydrogen passenger vehicle transportation pathways

    SciTech Connect

    Thomas, C.E.; James, B.D.; Lomax, F.D. Jr.; Kuhn, I.F. Jr.

    1998-08-01

    Hydrogen-powered fuel cell vehicles will reduce local air pollution, greenhouse gas emissions and oil imports. Other alternative vehicles such as gasoline- or methanol-powered fuel cell vehicles, natural gas vehicles and various hybrid electric vehicles with internal combustion engines may also provide significant environmental and national security advantages. This report summarizes a two-year project to compare the direct hydrogen fuel cell vehicle with other alternatives in terms of estimated cost and estimated societal benefits, all relative to a conventional gasoline-powered internal combustion engine vehicle. The cost estimates used in this study involve ground-up, detailed analysis of the major components of a fuel cell vehicle system, assuming mass production in automotive quantities. The authors have also estimated the cost of both gasoline and methanol onboard fuel processors, as well as the cost of stationary hydrogen fueling system components including steam methane reformers, electrolyzers, compressors and stationary storage systems. Sixteen different vehicle types are compared with respect to mass production cost, local air pollution and greenhouse gas emissions.

  20. An analysis of candidates for addition to the Clean Air Act list of hazardous air pollutants.

    PubMed

    Lunder, Sonya; Woodruff, Tracey J; Axelrad, Daniel A

    2004-02-01

    There are 188 air toxics listed as hazardous air pollutants (HAPs) in the Clean Air Act (CAA), based on their potential to adversely impact public health. This paper presents several analyses performed to screen potential candidates for addition to the HAPs list. We analyzed 1086 HAPs and potential HAPs, including chemicals regulated by the state of California or with emissions reported to the Toxics Release Inventory (TRI). HAPs and potential HAPs were ranked by their emissions to air, and by toxicity-weighted (tox-wtd) emissions for cancer and noncancer, using emissions information from the TRI and toxicity information from state and federal agencies. Separate consideration was given for persistent, bioaccumulative toxins (PBTs), reproductive or developmental toxins, and chemicals under evaluation for regulation as toxic air contaminants in California. Forty-four pollutants were identified as candidate HAPs based on three ranking analyses and whether they were a PBT or a reproductive or developmental toxin. Of these, nine qualified in two or three different rankings (ammonia [NH3], copper [Cu], Cu compounds, nitric acid [HNO3], N-methyl-2-pyrrolidone, sulfuric acid [H2SO4], vanadium [V] compounds, zinc [Zn], and Zn compounds). This analysis suggests further evaluation of several pollutants for possible addition to the CAA list of HAPs.

  1. In silico tools for the analysis of antibiotic biosynthetic pathways.

    PubMed

    Weber, Tilmann

    2014-05-01

    Natural products of bacteria and fungi are the most important source for antimicrobial drug leads. For decades, such compounds were exclusively found by chemical/bioactivity-guided screening approaches. The rapid progress in sequencing technologies only recently allowed the development of novel screening methods based on the genome sequences of potential producing organisms. The basic principle of such genome mining approaches is to identify genes, which are involved in the biosynthesis of such molecules, and to predict the products of the identified pathways. Thus, bioinformatics methods and tools are crucial for genome mining. In this review, a comprehensive overview is given on programs and databases for the identification and analysis of antibiotic biosynthesis gene clusters in genomic data.

  2. Decision Analysis Tool to Compare Energy Pathways for Transportation

    SciTech Connect

    Bloyd, Cary N.

    2010-06-30

    With the goals of reducing greenhouse gas emissions, oil imports, and energy costs, a wide variety of automotive technologies are proposed to replace the traditional gasoline-powered internal combustion engine (g-ICE). Biomass is seen as an important domestic energy feedstock, and there are multiple pathways in which it can be linked to the transport sector. Contenders include the use of cellulosic ethanol from biomass to replace gasoline or the use of a biomass-fueled combined cycle electrical power generation facility in conjunction plug-in hybrid electric vehicles (PHEVs). This paper reviews a project that is developing a scenario decision analysis tool to assist policy makers, program managers, and others to obtain a better understanding of these uncertain possibilities and how they may interact over time.

  3. Release criteria and pathway analysis for radiological remediation

    SciTech Connect

    Subbaraman, G.; Tuttle, R.J.; Oliver, B.M. . Rocketdyne Div.); Devgun, J.S. )

    1991-01-01

    Site-specific activity concentrations were derived for soils contaminated with mixed fission products (MFP), or uranium-processing residues, using the Department of Energy (DOE) pathway analysis computer code RESRAD at four different sites. The concentrations and other radiological parameters, such as limits on background-subtracted gamma exposure rate were used as the basis to arrive at release criteria for two of the sites. Valid statistical parameters, calculated for the distribution of radiological data obtained from site surveys, were then compared with the criteria to determine releasability or need for further decontamination. For the other two sites, RESRAD has been used as a preremediation planning tool to derive residual material guidelines for uranium. 11 refs., 4 figs., 3 tabs.

  4. Modal analysis of PATHFINDER unmanned air vehicle

    SciTech Connect

    Woehrle, T.G.; Costerus, B.W.; Lee, C.L.

    1994-10-19

    An experimental modal analysis was performed on PATHFINDER, a 450-lb, 100-ft wing span, flying-wing-design aircraft powered by solar/electric motors. The aircraft was softly suspended and then excited using random input from a long-stroke shaker. Modal data was taken from 92 measurement locations on the aircraft using newly designed, lightweight, tri-axial accelerometers. A conventional PC-based data acquisition system provided data handling. Modal parameters were calculated, and animated mode shapes were produced using SMS STARStruct{trademark} Modal Analysis System software. The modal parameters will be used for validation of finite element models, optimum placement of onboard accelerometers during flight testing, and vibration isolation design of sensor platforms.

  5. Comparative International Air Cargo Solutions: The Pathway to a Resilient, Adaptable, Balanced and Sustainable Secure Global Air Cargo Supply Chain

    DTIC Science & Technology

    2013-12-01

    according to the Center for Risk and Economic Analysis of Terrorism Events at the University of California. For the past three decades, terrorists have... terrorist organizations have regularly targeted U.S. citizens and its economy by attempting to detonate explosive devices on passenger and cargo...determined by START “that IEDs were the most common weapons used in the 207 terrorist plots and attacks in the United States from 2001 to 2011.” In the past

  6. Analysis of modified wet-air oxidation for soil detoxification

    SciTech Connect

    Unterberg, W.; Willms, R.S.; Balinsky, A.M.; Reible, D.D.; Wetzel, D.M.

    1987-09-01

    This report presents the results of research on wet-air oxidation as a method for the destruction of hazardous wastes. For organics in the presence of large amounts of water, the water need not be vaporized during wet-air oxidation, an attractive characteristic for energy conservation. The feasibility of using wet-air oxidation was investigated in terms of the effects of temperature, pressure, and the presence or absence of soil on the oxidation rate of three model compounds. Wet-air oxidation is a semi-commercial process that has been used to treat a variety of weakly toxic chemical wastes and for the regeneration of activated carbon. In the study, wet-air oxidation research was carried out in a 1-liter batch reactor at temperatures from 130 to 275/sup 0/C and pressures from 703-1760 x 10/sup 3/ kg/sq m on three substances: m-xylene, tetrachloroethylene (TCE), and malathion, both with and without addition of soil. Any attempt to balance the effect of residence time and the cost of energy requires an accurate description of the oxidation kinetics for the compound or waste stream in question. Due to the sampling technique used during the investigation and the inherent nature of the wet-air oxidation process, a variety of potential problems with the interpretation and analysis of the raw concentration-time data were encountered during the study.

  7. HIGH SPEED GC/MS FOR AIR ANALYSIS

    EPA Science Inventory

    A high speed GC/MS system consisting of a gas chromatograph equipped with a narrow bandwidth injection accessory and using a time-of-flight mass spectrometer detector has been adapted for analysis of ambient whole air samples which have been collected in passivated canisters. ...

  8. An Analysis of the Air Conditioning, Refrigerating and Heating Occupation.

    ERIC Educational Resources Information Center

    Frass, Melvin R.; Krause, Marvin

    The general purpose of the occupational analysis is to provide workable, basic information dealing with the many and varied duties performed in the air conditioning, refrigerating, and heating occupation. The document opens with a brief introduction followed by a job description. The bulk of the document is presented in table form. Six duties are…

  9. Cognitive Task Analysis of Prioritization in Air Traffic Control.

    ERIC Educational Resources Information Center

    Redding, Richard E.; And Others

    A cognitive task analysis was performed to analyze the key cognitive components of the en route air traffic controllers' jobs. The goals were to ascertain expert mental models and decision-making strategies and to identify important differences in controller knowledge, skills, and mental models as a function of expertise. Four groups of…

  10. Air sampling and analysis in a rubber vulcanization area.

    PubMed

    Rappaport, S M; Fraser, D A

    1977-05-01

    Results of sampling and analysis of air in a rubber vulcanization area are described. Organic compounds were collected on activated charcoal, desorbed with carbon disulfide and analyzed by gas chromatography. Several previously identified substances were quantitated, including styrene, toluene, ethylbenzene, and several oligomers of 1,3-butadiene. Concentrations ranged from 0.007 to 1.1 ppm.

  11. Analysis on relationship between extreme pathways and correlated reaction sets

    PubMed Central

    Xi, Yanping; Chen, Yi-Ping Phoebe; Cao, Ming; Wang, Weirong; Wang, Fei

    2009-01-01

    Background Constraint-based modeling of reconstructed genome-scale metabolic networks has been successfully applied on several microorganisms. In constraint-based modeling, in order to characterize all allowable phenotypes, network-based pathways, such as extreme pathways and elementary flux modes, are defined. However, as the scale of metabolic network rises, the number of extreme pathways and elementary flux modes increases exponentially. Uniform random sampling solves this problem to some extent to study the contents of the available phenotypes. After uniform random sampling, correlated reaction sets can be identified by the dependencies between reactions derived from sample phenotypes. In this paper, we study the relationship between extreme pathways and correlated reaction sets. Results Correlated reaction sets are identified for E. coli core, red blood cell and Saccharomyces cerevisiae metabolic networks respectively. All extreme pathways are enumerated for the former two metabolic networks. As for Saccharomyces cerevisiae metabolic network, because of the large scale, we get a set of extreme pathways by sampling the whole extreme pathway space. In most cases, an extreme pathway covers a correlated reaction set in an 'all or none' manner, which means either all reactions in a correlated reaction set or none is used by some extreme pathway. In rare cases, besides the 'all or none' manner, a correlated reaction set may be fully covered by combination of a few extreme pathways with related function, which may bring redundancy and flexibility to improve the survivability of a cell. In a word, extreme pathways show strong complementary relationship on usage of reactions in the same correlated reaction set. Conclusion Both extreme pathways and correlated reaction sets are derived from the topology information of metabolic networks. The strong relationship between correlated reaction sets and extreme pathways suggests a possible mechanism: as a controllable unit, an

  12. Preferential Activation of the Hedgehog Pathway by Epigenetic Modulations in HPV Negative HNSCC Identified with Meta-Pathway Analysis

    PubMed Central

    Fertig, Elana J.; Markovic, Ana; Danilova, Ludmila V.; Gaykalova, Daria A.; Cope, Leslie; Chung, Christine H.; Ochs, Michael F.; Califano, Joseph A.

    2013-01-01

    Head and neck squamous cell carcinoma (HNSCC) is largely divided into two groups based on their etiology, human papillomavirus (HPV)-positive and –negative. Global DNA methylation changes are known to drive oncogene and tumor suppressor expression in primary HNSCC of both types. However, significant heterogeneity in DNA methylation within the groups results in different transcriptional profiles and clinical outcomes. We applied a meta-pathway analysis to link gene expression changes to DNA methylation in distinguishing HNSCC subtypes. This approach isolated specific epigenetic changes controlling expression in HPV− HNSCC that distinguish it from HPV+ HNSCC. Analysis of genes identified Hedgehog pathway activation specific to HPV− HNSCC. We confirmed that GLI1, the primary Hedgehog target, showed higher expression in tumors compared to normal samples with HPV− tumors having the highest GLI1 expression, suggesting that increased expression of GLI1 is a potential driver in HPV− HNSCC. Our algorithm for integration of DNA methylation and gene expression can infer biologically significant molecular pathways that may be exploited as therapeutics targets. Our results suggest that therapeutics targeting the Hedgehog pathway may be of benefit in HPV− HNSCC. Similar integrative analysis of high-throughput coupled DNA methylation and expression datasets may yield novel insights into deregulated pathways in other cancers. PMID:24223768

  13. Preferential activation of the hedgehog pathway by epigenetic modulations in HPV negative HNSCC identified with meta-pathway analysis.

    PubMed

    Fertig, Elana J; Markovic, Ana; Danilova, Ludmila V; Gaykalova, Daria A; Cope, Leslie; Chung, Christine H; Ochs, Michael F; Califano, Joseph A

    2013-01-01

    Head and neck squamous cell carcinoma (HNSCC) is largely divided into two groups based on their etiology, human papillomavirus (HPV)-positive and -negative. Global DNA methylation changes are known to drive oncogene and tumor suppressor expression in primary HNSCC of both types. However, significant heterogeneity in DNA methylation within the groups results in different transcriptional profiles and clinical outcomes. We applied a meta-pathway analysis to link gene expression changes to DNA methylation in distinguishing HNSCC subtypes. This approach isolated specific epigenetic changes controlling expression in HPV- HNSCC that distinguish it from HPV+ HNSCC. Analysis of genes identified Hedgehog pathway activation specific to HPV- HNSCC. We confirmed that GLI1, the primary Hedgehog target, showed higher expression in tumors compared to normal samples with HPV- tumors having the highest GLI1 expression, suggesting that increased expression of GLI1 is a potential driver in HPV- HNSCC. Our algorithm for integration of DNA methylation and gene expression can infer biologically significant molecular pathways that may be exploited as therapeutics targets. Our results suggest that therapeutics targeting the Hedgehog pathway may be of benefit in HPV- HNSCC. Similar integrative analysis of high-throughput coupled DNA methylation and expression datasets may yield novel insights into deregulated pathways in other cancers.

  14. Error analysis of supersonic air-to-air ejector schlieren pictures

    NASA Astrophysics Data System (ADS)

    Kolář, J.

    2013-04-01

    The scope of this article is focused on general analysis of errors and uncertainties possibly arising from CFD-to-schlieren pictures matching. Analysis is based on classic analytical equations. These are firstly evaluated with the presumption of constant density gradient along the ray course. In other words, the deflection of light-ray caused by density gradient is negligible in compare to the cross size of constant gradient area. It is the aim of this work to determine, whether this presumption is applicable in case of supersonic air-to-air ejector. The colour and black and white schlieren pictures are carried out and compared to CFD results. Simulations had covered various eddy viscosities. Computed pressure gradients are transformed into deflection angles and further to ray displacement. Resulting computed light- ray deflection is matched to experimental results

  15. Spacelab J air filter debris analysis

    NASA Technical Reports Server (NTRS)

    Obenhuber, Donald C.

    1993-01-01

    Filter debris from the Spacelab module SLJ of STS-49 was analyzed for microbial contamination. Debris for cabin and avionics filters was collected by Kennedy Space Center personnel on 1 Oct. 1992, approximately 5 days postflight. The concentration of microorganisms found was similar to previous Spacelab missions averaging 7.4E+4 CFU/mL for avionics filter debris and 4.5E+6 CFU/mL for the cabin filter debris. A similar diversity of bacterial types was found in the two filters. Of the 13 different bacterial types identified from the cabin and avionics samples, 6 were common to both filters. The overall analysis of these samples as compared to those of previous missions shows no significant differences.

  16. Analysis of flight equipment purchasing practices of representative air carriers

    NASA Technical Reports Server (NTRS)

    1977-01-01

    The process through which representative air carriers decide whether or not to purchase flight equipment was investigated as well as their practices and policies in retiring surplus aircraft. An analysis of the flight equipment investment decision process in ten airlines shows that for the airline industry as a whole, the flight equipment investment decision is in a state of transition from a wholly informal process in earliest years to a much more organized and structured process in the future. Individual air carriers are in different stages with respect to the formality and sophistication associated with the flight equipment investment decision.

  17. Automated Retinofugal Visual Pathway Reconstruction with Multi-shell HARDI and FOD-based Analysis

    PubMed Central

    Kammen, Alexandra; Law, Meng; Tjan, Bosco S.; Toga, Arthur W.; Shi, Yonggang

    2015-01-01

    Diffusion MRI tractography provides a non-invasive modality to examine the human retinofugal projection, which consists of the optic nerves, optic chiasm, optic tracts, the lateral geniculate nuclei (LGN) and the optic radiations. However, the pathway has several anatomic features that make it particularly challenging to study with tractography, including its location near blood vessels and bone-air interface at the base of the cerebrum, crossing fibers at the chiasm, somewhat-tortuous course around the temporal horn via Meyer’s Loop, and multiple closely neighboring fiber bundles. To date, these unique complexities of the visual pathway have impeded the development of a robust and automated reconstruction method using tractography. To overcome these challenges, we develop a novel, fully automated system to reconstruct the retinofugal visual pathway from high-resolution diffusion imaging data. Using multi-shell, high angular resolution diffusion imaging (HARDI) data, we reconstruct precise fiber orientation distributions (FODs) with high order spherical harmonics (SPHARM) to resolve fiber crossings, which allows the tractography algorithm to successfully navigate the complicated anatomy surrounding the retinofugal pathway. We also develop automated algorithms for the identification of ROIs used for fiber bundle reconstruction. In particular, we develop a novel approach to extract the LGN region of interest (ROI) based on intrinsic shape analysis of a fiber bundle computed from a seed region at the optic chiasm to a target at the primary visual cortex. By combining automatically identified ROIs and FOD-based tractography, we obtain a fully automated system to compute the main components of the retinofugal pathway, including the optic tract and the optic radiation. We apply our method to the multi-shell HARDI data of 215 subjects from the Human Connectome Project (HCP). Through comparisons with post-mortem dissection measurements, we demonstrate the retinotopic

  18. Pathway Analysis Based on a Genome-Wide Association Study of Polycystic Ovary Syndrome

    PubMed Central

    Shim, Unjin; Kim, Han-Na; Lee, Hyejin; Oh, Jee-Young

    2015-01-01

    Background Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders in women of reproductive age, and it is affected by both environmental and genetic factors. Although the genetic component of PCOS is evident, studies aiming to identify susceptibility genes have shown controversial results. This study conducted a pathway-based analysis using a dataset obtained through a genome-wide association study (GWAS) to elucidate the biological pathways that contribute to PCOS susceptibility and the associated genes. Methods We used GWAS data on 636,797 autosomal single nucleotide polymorphisms (SNPs) from 1,221 individuals (432 PCOS patients and 789 controls) for analysis. A pathway analysis was conducted using meta-analysis gene-set enrichment of variant associations (MAGENTA). Top-ranking pathways or gene sets associated with PCOS were identified, and significant genes within the pathways were analyzed. Results The pathway analysis of the GWAS dataset identified significant pathways related to oocyte meiosis and the regulation of insulin secretion by acetylcholine and free fatty acids (all nominal gene-set enrichment analysis (GSEA) P-values < 0.05). In addition, INS, GNAQ, STXBP1, PLCB3, PLCB2, SMC3 and PLCZ1 were significant genes observed within the biological pathways (all gene P-values < 0.05). Conclusions By applying MAGENTA pathway analysis to PCOS GWAS data, we identified significant pathways and candidate genes involved in PCOS. Our findings may provide new leads for understanding the mechanisms underlying the development of PCOS. PMID:26308735

  19. Integrated Analysis Identifies Interaction Patterns between Small Molecules and Pathways

    PubMed Central

    Li, Yan; Li, Weiguo; Chen, Xin; Sun, Jiatong; Chen, Huan; Lv, Sali

    2014-01-01

    Previous studies have indicated that the downstream proteins in a key pathway can be potential drug targets and that the pathway can play an important role in the action of drugs. So pathways could be considered as targets of small molecules. A link map between small molecules and pathways was constructed using gene expression profile, pathways, and gene expression of cancer cell line intervened by small molecules and then we analysed the topological characteristics of the link map. Three link patterns were identified based on different drug discovery implications for breast, liver, and lung cancer. Furthermore, molecules that significantly targeted the same pathways tended to treat the same diseases. These results can provide a valuable reference for identifying drug candidates and targets in molecularly targeted therapy. PMID:25114931

  20. Air Pollution and Quality of Sperm: A Meta-Analysis

    PubMed Central

    Fathi Najafi, Tahereh; Latifnejad Roudsari, Robab; Namvar, Farideh; Ghavami Ghanbarabadi, Vahid; Hadizadeh Talasaz, Zahra; Esmaeli, Mahin

    2015-01-01

    Context: Air pollution is common in all countries and affects reproductive functions in men and women. It particularly impacts sperm parameters in men. This meta-analysis aimed to examine the impact of air pollution on the quality of sperm. Evidence Acquisition: The scientific databases of Medline, PubMed, Scopus, Google scholar, Cochrane Library, and Elsevier were searched to identify relevant articles published between 1978 to 2013. In the first step, 76 articles were selected. These studies were ecological correlation, cohort, retrospective, cross-sectional, and case control ones that were found through electronic and hand search of references about air pollution and male infertility. The outcome measurement was the change in sperm parameters. A total of 11 articles were ultimately included in a meta-analysis to examine the impact of air pollution on sperm parameters. The authors applied meta-analysis sheets from Cochrane library, then data extraction, including mean and standard deviation of sperm parameters were calculated and finally their confidence interval (CI) were compared to CI of standard parameters. Results: The CI for pooled means were as follows: 2.68 ± 0.32 for ejaculation volume (mL), 62.1 ± 15.88 for sperm concentration (million per milliliter), 39.4 ± 5.52 for sperm motility (%), 23.91 ± 13.43 for sperm morphology (%) and 49.53 ± 11.08 for sperm count. Conclusions: The results of this meta-analysis showed that air pollution reduces sperm motility, but has no impact on the other sperm parameters of spermogram. PMID:26023349

  1. Thermohydraulic analysis of the cooling air flow in a rack

    NASA Astrophysics Data System (ADS)

    Natusch, Andreas; Huchler, Markus

    Manned space laboratories like the US Space Station Freedom or the European COLUMBUS APM are equipped with so-called racks for subsystem and payload accommodation. An important resource is air for cooling the unit internal heat sources, the avionics air. Each unit inside the rack must be supplied with sufficient amount of air to cool down the unit to the allowable maximum temperature. In the course of the COLUMBUS Environmental Control and Life Support Subsystem (ECLSS) project, a thermohydraulic mathematical model (THMM) of a representative COLUMBUS rack was developed to analyze and optimize the distribution of avionic air inside this rack. A sensitivity and accuracy study was performed to determine the accuracy range of the calculated avionics flow rate distribution to the units. These calculations were then compared to measurement results gained in a rack airflow distribution test, which was performed with an equipped COLUMBUS subsystem rack to show the pressure distribution inside the rack. In addition to that cold flow study, the influence of the avionics air heating due to the unit dissipations on the airflow distribution and the cooling tenmperature was investigated in a detailed warm flow analysis.

  2. Analysis of MINIE2013 Explosion Air-Blast Data

    SciTech Connect

    Schnurr, Julie M.; Rodgers, Arthur J.; Kim, Keehoon; Ford, Sean R.; Ramirez, Abelardo L.

    2016-10-14

    We report analysis of air-blast overpressure measurements from the MINIE2013 explosive experiments. The MINIE2013 experiment involved a series of nearly 70 near-surface (height-ofburst, HOB, ranging from -1 to +4 m) low-yield (W=2-20 kg TNT equivalent) chemical highexplosives tests that were recorded at local distances (230 m – 28.5 km). Many of the W and HOB combinations were repeated, allowing for quantification of the variability in air-blast features and corresponding yield estimates. We measured canonical signal features (peak overpressure, impulse per unit area, and positive pulse duration) from the air-blast data and compared these to existing air-blast models. Peak overpressure measurements showed good agreement with the models at close ranges but tended to attenuate more rapidly at longer range (~ 1 km), which is likely caused by upward refraction of acoustic waves due to a negative vertical gradient of sound speed. We estimated yields of the MINIE2013 explosions using the Integrated Yield Determination Tool (IYDT). Errors of the estimated yields were on average within 30% of the reported yields, and there were no significant differences in the accuracy of the IYDT predictions grouped by yield. IYDT estimates tend to be lower than ground truth yields, possibly because of reduced overpressure amplitudes by upward refraction. Finally, we report preliminary results on a development of a new parameterized air-blast waveform.

  3. Pathway-based analysis of primary biliary cirrhosis genome-wide association studies.

    PubMed

    Kar, S P; Seldin, M F; Chen, W; Lu, E; Hirschfield, G M; Invernizzi, P; Heathcote, J; Cusi, D; Gershwin, M E; Siminovitch, K A; Amos, C I

    2013-04-01

    Genome-wide association studies (GWAS) have successfully identified several loci associated with primary biliary cirrhosis (PBC) risk. Pathway analysis complements conventional GWAS analysis. We applied the recently developed linear combination test for pathways to datasets drawn from independent PBC GWAS in Italian and Canadian subjects. Of the Kyoto Encyclopedia of Genes and Genomes and BioCarta pathways tested, 25 pathways in the Italian dataset (449 cases, 940 controls) and 26 pathways in the Canadian dataset (530 cases, 398 controls) were associated with PBC susceptibility (P<0.05). After correcting for multiple comparisons, only the eight most significant pathways in the Italian dataset had FDR <0.25 with tumor necrosis factor/stress-related signaling emerging as the top pathway (P=7.38 × 10⁻⁴, FDR=0.18). Two pathways, phosphatidylinositol signaling and hedgehog signaling, were replicated in both datasets (P<0.05), and subjected to two additional complementary pathway tests. Both pathway signals remained significant in the Italian dataset on modified gene set enrichment analysis (P<0.05). In both GWAS, variants nominally associated with PBC were significantly overrepresented in the phosphatidylinositol pathway (Fisher exact P<0.05). These results point to established and novel pathway-level associations with inherited predisposition to PBC that, on further independent replication and functional validation, may provide fresh insights into PBC etiology.

  4. Pathway-based analysis of primary biliary cirrhosis genome-wide association studies

    PubMed Central

    Kar, SP; Seldin, MF; Chen, W; Lu, E; Hirschfield, GM; Invernizzi, P; Heathcote, J; Cusi, D; Gershwin, ME; Siminovitch, KA; Amos, CI

    2013-01-01

    Genome-wide association studies (GWAS) have successfully identified several loci associated with primary biliary cirrhosis (PBC) risk. Pathway analysis complements conventional GWAS analysis. We applied the recently developed linear combination test for pathways to datasets drawn from independent PBC GWAS in Italian and Canadian subjects. Of the Kyoto Encyclopedia of Genes and Genomes and BioCarta pathways tested, 25 pathways in the Italian dataset (449 cases, 940 controls) and 26 pathways in the Canadian dataset (530 cases, 398 controls) were associated with PBC susceptibility (P < 0.05). After correcting for multiple comparisons, only the eight most significant pathways in the Italian dataset had FDR < 0.25 with tumor necrosis factor/stress-related signaling emerging as the top pathway (P = 7.38 × 10−4, FDR = 0.18). Two pathways, phosphatidylinositol signaling and hedgehog signaling, were replicated in both datasets (P < 0.05), and subjected to two additional complementary pathway tests. Both pathway signals remained significant in the Italian dataset on modified gene set enrichment analysis (P < 0.05). In both GWAS, variants nominally associated with PBC were significantly overrepresented in the phosphatidylinositol pathway (Fisher exact P < 0.05). These results point to established and novel pathway-level associations with inherited predisposition to PBC that on further independent replication and functional validation, may provide fresh insights into PBC etiology. PMID:23392275

  5. ESEA: Discovering the Dysregulated Pathways based on Edge Set Enrichment Analysis

    PubMed Central

    Han, Junwei; Shi, Xinrui; Zhang, Yunpeng; Xu, Yanjun; Jiang, Ying; Zhang, Chunlong; Feng, Li; Yang, Haixiu; Shang, Desi; Sun, Zeguo; Su, Fei; Li, Chunquan; Li, Xia

    2015-01-01

    Pathway analyses are playing an increasingly important role in understanding biological mechanism, cellular function and disease states. Current pathway-identification methods generally focus on only the changes of gene expression levels; however, the biological relationships among genes are also the fundamental components of pathways, and the dysregulated relationships may also alter the pathway activities. We propose a powerful computational method, Edge Set Enrichment Analysis (ESEA), for the identification of dysregulated pathways. This provides a novel way of pathway analysis by investigating the changes of biological relationships of pathways in the context of gene expression data. Simulation studies illustrate the power and performance of ESEA under various simulated conditions. Using real datasets from p53 mutation, Type 2 diabetes and lung cancer, we validate effectiveness of ESEA in identifying dysregulated pathways. We further compare our results with five other pathway enrichment analysis methods. With these analyses, we show that ESEA is able to help uncover dysregulated biological pathways underlying complex traits and human diseases via specific use of the dysregulated biological relationships. We develop a freely available R-based tool of ESEA. Currently, ESEA can support pathway analysis of the seven public databases (KEGG; Reactome; Biocarta; NCI; SPIKE; HumanCyc; Panther). PMID:26267116

  6. A Wavelet Analysis Approach for Categorizing Air Traffic Behavior

    NASA Technical Reports Server (NTRS)

    Drew, Michael; Sheth, Kapil

    2015-01-01

    In this paper two frequency domain techniques are applied to air traffic analysis. The Continuous Wavelet Transform (CWT), like the Fourier Transform, is shown to identify changes in historical traffic patterns caused by Traffic Management Initiatives (TMIs) and weather with the added benefit of detecting when in time those changes take place. Next, with the expectation that it could detect anomalies in the network and indicate the extent to which they affect traffic flows, the Spectral Graph Wavelet Transform (SGWT) is applied to a center based graph model of air traffic. When applied to simulations based on historical flight plans, it identified the traffic flows between centers that have the greatest impact on either neighboring flows, or flows between centers many centers away. Like the CWT, however, it can be difficult to interpret SGWT results and relate them to simulations where major TMIs are implemented, and more research may be warranted in this area. These frequency analysis techniques can detect off-nominal air traffic behavior, but due to the nature of air traffic time series data, so far they prove difficult to apply in a way that provides significant insight or specific identification of traffic patterns.

  7. Regulatory pathway analysis by high-throughput in situ hybridization

    SciTech Connect

    Visel, Axel; Carson, James P.; Oldekamp, Judit; Warnecke, Marei; Jakubcakova, Vladimira; Zhou, Xunlei; Shaw, Chad; Alvarez-Bolado, Gonzalo; Eichele, Gregor

    2007-10-01

    Automated in situ hybridization (ISH) permits construction of comprehensive atlases of gene expression patterns in mammals. When web-accessible, such atlases become searchable digital expression maps of individual genes and offer an entryway to elucidate genetic interactions and signaling pathways. An atlas housing ~1,000 spatial gene expression patterns of the mid-gestation mouse embryo was generated. Patterns were textually annotated using a controlled vocabulary comprising 90 anatomical features. Hierarchical clustering of annotations was carried out using distance scores calculated from the similarity between pairs of patterns across all anatomical structures. This ordered hundreds of complex expression patterns into a matrix that reflected the embryonic architecture and the relatedness of patterns of expression. Clustering yielded twelve distinct groups of expression pattern. Because of similarity of expression patterns within a group, members of this group may be components of regulatory cascades. We focused on one group, which is composed of 83 genes, including Pax6, an evolutionary conserved transcriptional master mediator of the development. Using functional studies, ISH on Pax6-deficient embryos and Pax6 binding site identification and validation by means of electromobility shift assays, we identified numerous genes that are transcriptionally regulated by Pax6. Hence cluster analysis of annotated gene expression patterns obtained by robotic ISH is an entryway for identification of components of signaling cascades in mammals.

  8. Regulatory Pathway Analysis by High-Throughput In Situ Hybridization

    PubMed Central

    Visel, Axel; Carson, James; Oldekamp, Judit; Warnecke, Marei; Jakubcakova, Vladimira; Zhou, Xunlei; Shaw, Chad A; Alvarez-Bolado, Gonzalo; Eichele, Gregor

    2007-01-01

    Automated in situ hybridization enables the construction of comprehensive atlases of gene expression patterns in mammals. Such atlases can become Web-searchable digital expression maps of individual genes and thus offer an entryway to elucidate genetic interactions and signaling pathways. Towards this end, an atlas housing ∼1,000 spatial gene expression patterns of the midgestation mouse embryo was generated. Patterns were textually annotated using a controlled vocabulary comprising >90 anatomical features. Hierarchical clustering of annotations was carried out using distance scores calculated from the similarity between pairs of patterns across all anatomical structures. This process ordered hundreds of complex expression patterns into a matrix that reflects the embryonic architecture and the relatedness of patterns of expression. Clustering yielded 12 distinct groups of expression patterns. Because of the similarity of expression patterns within a group, members of each group may be components of regulatory cascades. We focused on the group containing Pax6, an evolutionary conserved transcriptional master mediator of development. Seventeen of the 82 genes in this group showed a change of expression in the developing neocortex of Pax6-deficient embryos. Electromobility shift assays were used to test for the presence of Pax6-paired domain binding sites. This led to the identification of 12 genes not previously known as potential targets of Pax6 regulation. These findings suggest that cluster analysis of annotated gene expression patterns obtained by automated in situ hybridization is a novel approach for identifying components of signaling cascades. PMID:17953485

  9. Supply Chain Sustainability Analysis of Three Biofuel Pathways

    SciTech Connect

    Jacob J. Jacobson; Erin Searcy; Kara Cafferty; Jennifer B. Dunn; Michael Johnson; Zhichao Wang; Michael Wang; Mary Biddy; Abhijit Dutta; Daniel Inman; Eric Tan; Sue Jones; Lesley Snowden-Swan

    2013-11-01

    The Department of Energy’s (DOE) Bioenergy Technologies Office (BETO) collaborates with industrial, agricultural, and non-profit partners to develop and deploy biofuels and other biologically-derived products. As part of this effort, BETO and its national laboratory teams conduct in-depth techno-economic assessments (TEA) of technologies to produce biofuels as part state of technology (SOT) analyses. An SOT assesses progress within and across relevant technology areas based on actual experimental results relative to technical targets and cost goals from design cases and includes technical, economic, and environmental criteria as available. Overall assessments of biofuel pathways begin with feedstock production and the logistics of transporting the feedstock from the farm or plantation to the conversion facility or biorefinery. The conversion process itself is modeled in detail as part of the SOT analysis. The teams then develop an estimate of the biofuel minimum selling price (MSP) and assess the cost competitiveness of the biofuel with conventional fuels such as gasoline.

  10. Radiological environmental pathway screening analysis for the Feed Materials Production Center (FMPC)

    SciTech Connect

    Eckart, R.; Carr, D.; Conner, B.; Janke, R.; Janke, R.

    1989-11-01

    The University of Cincinnati is working with the Westinghouse Materials Company of Ohio (WMCO) to develop remedial action residual radioactive material soil guidelines for the Feed Materials Production Center (FMPC). As a first step in developing these soil guidelines, a radiological environmental pathway screening analysis was performed. The purpose of the pathway screening analysis was to identify the radionuclides and environmental pathways that would lead to the highest exposure or dose to humans from residual radioactivity in the soil at the FMPC. In addition, the screening analysis identifies those pathways that are critical to a particular radioisotope.

  11. Gene expression analysis reveals the dysregulation of immune and metabolic pathways in Alzheimer's disease

    PubMed Central

    Li, Zhiyan; Xu, Panpan; Yao, Lifen

    2016-01-01

    In recent years, several pathway analyses of genome-wide association studies reported the involvement of metabolic and immune pathways in Alzheimer's disease (AD). Until now, the exact mechanisms of these pathways in AD are still unclear. Here, we conducted a pathway analysis of a whole genome AD case-control expression dataset (n=41, 25 AD cases and 16 controls) from the human temporal cortex tissue. Using the differently expressed AD genes, we identified significant KEGG pathways related to metabolism and immune processes. Using the up- and down- regulated AD gene list, we further found up-regulated AD gene were significantly enriched in immune and metabolic pathways. We further compare the immune and metabolic KEGG pathways from the expression dataset with those from previous GWAS datasets, and found that most of these pathways are shared in both GWAS and expression datasets. PMID:27732949

  12. Path Similarity Analysis: A Method for Quantifying Macromolecular Pathways

    PubMed Central

    Seyler, Sean L.; Kumar, Avishek; Thorpe, M. F.; Beckstein, Oliver

    2015-01-01

    Diverse classes of proteins function through large-scale conformational changes and various sophisticated computational algorithms have been proposed to enhance sampling of these macromolecular transition paths. Because such paths are curves in a high-dimensional space, it has been difficult to quantitatively compare multiple paths, a necessary prerequisite to, for instance, assess the quality of different algorithms. We introduce a method named Path Similarity Analysis (PSA) that enables us to quantify the similarity between two arbitrary paths and extract the atomic-scale determinants responsible for their differences. PSA utilizes the full information available in 3N-dimensional configuration space trajectories by employing the Hausdorff or Fréchet metrics (adopted from computational geometry) to quantify the degree of similarity between piecewise-linear curves. It thus completely avoids relying on projections into low dimensional spaces, as used in traditional approaches. To elucidate the principles of PSA, we quantified the effect of path roughness induced by thermal fluctuations using a toy model system. Using, as an example, the closed-to-open transitions of the enzyme adenylate kinase (AdK) in its substrate-free form, we compared a range of protein transition path-generating algorithms. Molecular dynamics-based dynamic importance sampling (DIMS) MD and targeted MD (TMD) and the purely geometric FRODA (Framework Rigidity Optimized Dynamics Algorithm) were tested along with seven other methods publicly available on servers, including several based on the popular elastic network model (ENM). PSA with clustering revealed that paths produced by a given method are more similar to each other than to those from another method and, for instance, that the ENM-based methods produced relatively similar paths. PSA applied to ensembles of DIMS MD and FRODA trajectories of the conformational transition of diphtheria toxin, a particularly challenging example, showed that

  13. Pathway analysis of body mass index genome-wide association study highlights risk pathways in cardiovascular disease

    PubMed Central

    Zhao, Xin; Gu, Jinxia; Li, Ming; Xi, Jie; Sun, Wenyu; Song, Guangmin; Liu, Guiyou

    2015-01-01

    Cardiovascular disease (CVD) is a class of diseases that involve the heart or blood vessels. It is reported that body mass index (BMI) is risk factor for CVD. Genome-wide association studies (GWAS) have recently provided rapid insights into genetics of CVD and its risk factors. However, the specific mechanisms how BMI influences CVD risk are largely unknown. We think that BMI may influences CVD risk by shared genetic pathways. In order to confirm this view, we conducted a pathway analysis of BMI GWAS, which examined approximately 329,091 single nucleotide polymorphisms from 4763 samples. We identified 31 significant KEGG pathways. There is literature evidence supporting the involvement of GnRH signaling, vascular smooth muscle contraction, dilated cardiomyopathy, Gap junction, Wnt signaling, Calcium signaling and Chemokine signaling in CVD. Collectively, our study supports the potential role of the CVD risk pathways in BMI. BMI may influence CVD risk by the shared genetic pathways. We believe that our results may advance our understanding of BMI mechanisms in CVD. PMID:26264282

  14. An Analysis of the Air Force Enlisted Performance Feedback System

    DTIC Science & Technology

    1992-09-01

    subjects giving and receiving the feedback from the various methods (DeGregorio and Fisher, 1988:605). The four types of techniques they studied in... receives some P.~ id~srn Hence, leadership gives support from upper-level ~potfo elw p no emphasis to a feedback management. Certain Io .a.........k...researchers’ analysis of the literature. The researchers found evidence that the new Air Force feedback system is an improvement over the old design. Under the

  15. Interlaboratory study of toxaphene analysis in ambient air

    NASA Astrophysics Data System (ADS)

    Bidleman, Terry F.; Cussion, Sylvia; Jantunen, Liisa M.

    An interlaboratory study was conducted for total toxaphene and selected congeners in an extract of ambient air from the southern United States. All participating labs were experienced in toxaphene analysis and used GC-MS techniques. Ten labs reported the concentration of total toxaphene in a technical toxaphene solution, with a 113% average recovery of the target value and 40% relative standard deviation (RSD). Only six of the 10 labs fell within ±30% of the target value, a criterion recommended by good laboratory practice standards. The interlaboratory RSD was 65% for total toxaphene in the air sample extract (lowered to 43% when one outlying lab was omitted). Nine labs reported the concentrations of five toxaphene components (B8-1413, B8-1414+B8-1945, B8-806+B8-809, B8-2229 and B9-1679) with 33-47% RSD for the technical toxaphene unknown and 34-62% for the air sample. The precision was poorer for a sixth component, congener B9-1025, which has a very low response by electron capture negative ion mass spectrometry (ECNI): 59% RSD for the technical toxaphene unknown and 196% for the air sample. Factors contributing to the interlaboratory variability for total toxaphene and single components are discussed, and follow-up studies are required to identify and minimize the causes of variability. Based on the average analysis, B8-1413 was enriched and B8-806+B8-809 was depleted in the air sample relative to the technical toxaphene standard.

  16. Comprehensive Analysis of Migration Pathways (CAMP): Contaminant Migration Pathways at Confined Dredged Material Disposal Facilities

    DTIC Science & Technology

    1990-09-01

    longer a contaminant loss pathway. 64. Suspended sediment/water interactions are difficult to model because of the complex nature of sediment...Brannon et al. 1976) and the sediment-specific interactions that contaminants exhibit (O’Connor and Connolly 1980). The complexity of the sediment matrix...water interactions in nonequilibrium situations. However, rate processes are much more complex than equilibrium approaches because they require knowledge

  17. Key genes and pathways in thyroid cancer based on gene set enrichment analysis.

    PubMed

    He, Wenwu; Qi, Bin; Zhou, Qiuxi; Lu, Chuansen; Huang, Qi; Xian, Lei; Chen, Mingwu

    2013-09-01

    The incidence of thyroid cancer and its associated morbidity has shown the most rapid increase among all cancers since 1982, but the mechanisms involved in thyroid cancer, particularly significant key genes induced in thyroid cancer, remain undefined. In many studies, gene probes have been used to search for key genes involved in causing and facilitating thyroid cancer. As a result, many possible virulence genes and pathways have been identified. However, these studies lack a case contrast for selecting the most possible virulence genes and pathways, as well as conclusive results with which to clarify the mechanisms of cancer development. In the present study, we used gene set enrichment and meta-analysis to select key genes and pathways. Based on gene set enrichment, we identified 5 downregulated and 4 upregulated mixed pathways in 6 tissue datasets. Based on the meta-analysis, there were 17 common pathways in the tissue datasets. One pathway, the p53 signaling pathway, which includes 13 genes, was identified by both the gene set enrichment analysis and meta-analysis. Genes are important elements that form key pathways. These pathways can induce the development of thyroid cancer later in life. The key pathways and genes identified in the present study can be used in the next stage of research, which will involve gene elimination and other methods of experimentation.

  18. Pathway analysis of genome-wide association datasets of personality traits.

    PubMed

    Kim, H-N; Kim, B-H; Cho, J; Ryu, S; Shin, H; Sung, J; Shin, C; Cho, N H; Sung, Y A; Choi, B-O; Kim, H-L

    2015-04-01

    Although several genome-wide association (GWA) studies of human personality have been recently published, genetic variants that are highly associated with certain personality traits remain unknown, due to difficulty reproducing results. To further investigate these genetic variants, we assessed biological pathways using GWA datasets. Pathway analysis using GWA data was performed on 1089 Korean women whose personality traits were measured with the Revised NEO Personality Inventory for the 5-factor model of personality. A total of 1042 pathways containing 8297 genes were included in our study. Of these, 14 pathways were highly enriched with association signals that were validated in 1490 independent samples. These pathways include association of: Neuroticism with axon guidance [L1 cell adhesion molecule (L1CAM) interactions]; Extraversion with neuronal system and voltage-gated potassium channels; Agreeableness with L1CAM interaction, neurotransmitter receptor binding and downstream transmission in postsynaptic cells; and Conscientiousness with the interferon-gamma and platelet-derived growth factor receptor beta polypeptide pathways. Several genes that contribute to top-ranked pathways in this study were previously identified in GWA studies or by pathway analysis in schizophrenia or other neuropsychiatric disorders. Here we report the first pathway analysis of all five personality traits. Importantly, our analysis identified novel pathways that contribute to understanding the etiology of personality traits.

  19. Theoretical and numerical analysis of the corneal air puff test

    NASA Astrophysics Data System (ADS)

    Simonini, Irene; Angelillo, Maurizio; Pandolfi, Anna

    2016-08-01

    Ocular analyzers are used in the current clinical practice to estimate, by means of a rapid air jet, the intraocular pressure and other eye's parameters. In this study, we model the biomechanical response of the human cornea to the dynamic test with two approaches. In the first approach, the corneal system undergoing the air puff test is regarded as a harmonic oscillator. In the second approach, we use patient-specific geometries and the finite element method to simulate the dynamic test on surgically treated corneas. In spite of the different levels of approximation, the qualitative response of the two models is very similar, and the most meaningful results of both models are not significantly affected by the inclusion of viscosity of the corneal material in the dynamic analysis. Finite element calculations reproduce the observed snap-through of the corneal shell, including two applanate configurations, and compare well with in vivo images provided by ocular analyzers, suggesting that the mechanical response of the cornea to the air puff test is actually driven only by the elasticity of the stromal tissue. These observations agree with the dynamic characteristics of the test, since the frequency of the air puff impulse is several orders of magnitude larger than the reciprocal of any reasonable relaxation time for the material, downplaying the role of viscosity during the fast snap-through phase.

  20. Aviation System Analysis Capability Air Carrier Investment Model-Cargo

    NASA Technical Reports Server (NTRS)

    Johnson, Jesse; Santmire, Tara

    1999-01-01

    The purpose of the Aviation System Analysis Capability (ASAC) Air Cargo Investment Model-Cargo (ACIMC), is to examine the economic effects of technology investment on the air cargo market, particularly the market for new cargo aircraft. To do so, we have built an econometrically based model designed to operate like the ACIM. Two main drivers account for virtually all of the demand: the growth rate of the Gross Domestic Product (GDP) and changes in the fare yield (which is a proxy of the price charged or fare). These differences arise from a combination of the nature of air cargo demand and the peculiarities of the air cargo market. The net effect of these two factors are that sales of new cargo aircraft are much less sensitive to either increases in GDP or changes in the costs of labor, capital, fuel, materials, and energy associated with the production of new cargo aircraft than the sales of new passenger aircraft. This in conjunction with the relatively small size of the cargo aircraft market means technology improvements to the cargo aircraft will do relatively very little to spur increased sales of new cargo aircraft.

  1. Why social network analysis is important to Air Force applications

    NASA Astrophysics Data System (ADS)

    Havig, Paul R.; McIntire, John P.; Geiselman, Eric; Mohd-Zaid, Fairul

    2012-06-01

    Social network analysis is a powerful tool used to help analysts discover relationships amongst groups of people as well as individuals. It is the mathematics behind such social networks as Facebook and MySpace. These networks alone cause a huge amount of data to be generated and the issue is only compounded once one adds in other electronic media such as e-mails and twitter. In this paper we outline the basics of social network analysis and how it may be used in current and future Air Force applications.

  2. Analysis of Ah receptor pathway activation by brominated flame retardants.

    PubMed

    Brown, David J; Van Overmeire, Ilse; Goeyens, Leo; Denison, Michael S; De Vito, Michael J; Clark, George C

    2004-06-01

    Brominated flame-retardants (BFRs) are used as additives in plastics to decrease the rate of combustion of these materials, leading to greater consumer safety. As the use of plastics has increased, the production and use of flame-retardants has also grown. Many BFRs are persistent and have been detected in environmental samples, raising concerns about the biological/toxicological risk associated with their use. Most BFRs appear to be non-toxic, however there is still some concern that these compounds, or possible contaminants in BFRs mixtures could interact with cellular receptors. In this study we have examined the interaction of decabromodiphenyl ether, Firemaster BP4A (tetrabromobisphenol A), Firemaster PHT4 (tetrabromophthalic anhydride), hexabromobenzene, pentabromotoluene, decabromobiphenyl, Firemaster BP-6 (2,2',4,4',5,5'-hexabromobiphenyl) and possible contaminants of BFR mixtures with the Ah receptor. Receptor binding and activation was examined using the Gel Retardation Assay and increased expression of dioxin responsive genes was detected using the reporter gene based CALUX assay. The results demonstrate the ability of BFRs to activate the AhR signal transduction pathway at moderate to high concentrations as assessed using both assays. AhR-dependent activation by BFRs may be due in part to contaminants present in commercial/technical mixtures. This was suggested by our comparative analysis of Firemaster BP-6 versus its primary component 2,2',4,4',5,5'-hexabromobiphenyl. Some technical mixtures of brominated flame-retardants contain brominated biphenyls, dioxins or dibenzofurans as contaminants. When tested in the CALUX assay these compounds were found to be equivalent to, or more active than their chlorinated analogues. Relative effective potency values were determined from dose response curves for these brominated HAHs.

  3. Methods and approaches in the topology-based analysis of biological pathways

    PubMed Central

    Mitrea, Cristina; Taghavi, Zeinab; Bokanizad, Behzad; Hanoudi, Samer; Tagett, Rebecca; Donato, Michele; Voichiţa, Călin; Drăghici, Sorin

    2013-01-01

    The goal of pathway analysis is to identify the pathways significantly impacted in a given phenotype. Many current methods are based on algorithms that consider pathways as simple gene lists, dramatically under-utilizing the knowledge that such pathways are meant to capture. During the past few years, a plethora of methods claiming to incorporate various aspects of the pathway topology have been proposed. These topology-based methods, sometimes referred to as “third generation,” have the potential to better model the phenomena described by pathways. Although there is now a large variety of approaches used for this purpose, no review is currently available to offer guidance for potential users and developers. This review covers 22 such topology-based pathway analysis methods published in the last decade. We compare these methods based on: type of pathways analyzed (e.g., signaling or metabolic), input (subset of genes, all genes, fold changes, gene p-values, etc.), mathematical models, pathway scoring approaches, output (one or more pathway scores, p-values, etc.) and implementation (web-based, standalone, etc.). We identify and discuss challenges, arising both in methodology and in pathway representation, including inconsistent terminology, different data formats, lack of meaningful benchmarks, and the lack of tissue and condition specificity. PMID:24133454

  4. Chemogenomic analysis of neuronal differentiation with pathway changes in PC12 cells.

    PubMed

    Lin, Jack Yu-Shih; Wu, Chien Liang; Liao, Chia Nan; Higuchi, Akon; Ling, Qing-Dong

    2016-01-01

    The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway database creates networks from interrelations between molecular biology and underlying chemical elements. This allows for analysis of biologic networks, genomic information, and higher-order functional information at a system level. Through high throughput experiments and system biology analysis, we investigated the genes and pathways associated with NGF induced neuronal differentiation. We performed microarray experiments and used the KEGG database, system biology analysis, and annotation of pathway functions to study NGF-induced differentiation in PC12 cells. We identified 2020 NGF-induced genes with altered expressions over time. Cross-matching with the KEGG database revealed 830 genes; among which, 395 altered genes were found to have a 2-fold increase in gene expression over a two-hour period. We then identified 191 associated biologic pathways in the KEGG database; the top 15 pathways showed correlation with neural differentiation. These included the neurotrophin pathways, mitogen-activated protein kinase (MAPK) pathways, genes associated with axonal guidance and the Wnt pathways. The activation of these pathways synchronized with nerve growth factor (NGF)-induced differentiation in PC12 cells. In summary, we have established a model system that allows one to systematically characterize the functional pathway changes in a group of neuronal population after an external stimulus.

  5. Pathway Analysis for Genome-Wide Association Study of Lung Cancer in Han Chinese Population

    PubMed Central

    Wu, Chen; Jin, Guangfu; Dai, Juncheng; Wang, Cheng; Hu, Lingmin; Gou, Jianwei; Qian, Chen; Bai, Jianling; Wu, Tangchun; Hu, Zhibin; Lin, Dongxin; Shen, Hongbing; Chen, Feng

    2013-01-01

    Genome-wide association studies (GWAS) have identified a number of genetic variants associated with lung cancer risk. However, these loci explain only a small fraction of lung cancer hereditability and other variants with weak effect may be lost in the GWAS approach due to the stringent significance level after multiple comparison correction. In this study, in order to identify important pathways involving the lung carcinogenesis, we performed a two-stage pathway analysis in GWAS of lung cancer in Han Chinese using gene set enrichment analysis (GSEA) method. Predefined pathways by BioCarta and KEGG databases were systematically evaluated on Nanjing study (Discovery stage: 1,473 cases and 1,962 controls) and the suggestive pathways were further to be validated in Beijing study (Replication stage: 858 cases and 1,115 controls). We found that four pathways (achPathway, metPathway, At1rPathway and rac1Pathway) were consistently significant in both studies and the P values for combined dataset were 0.012, 0.010, 0.022 and 0.005 respectively. These results were stable after sensitivity analysis based on gene definition and gene overlaps between pathways. These findings may provide new insights into the etiology of lung cancer. PMID:23469231

  6. Calibration and Data Analysis of the MC-130 Air Balance

    NASA Technical Reports Server (NTRS)

    Booth, Dennis; Ulbrich, N.

    2012-01-01

    Design, calibration, calibration analysis, and intended use of the MC-130 air balance are discussed. The MC-130 balance is an 8.0 inch diameter force balance that has two separate internal air flow systems and one external bellows system. The manual calibration of the balance consisted of a total of 1854 data points with both unpressurized and pressurized air flowing through the balance. A subset of 1160 data points was chosen for the calibration data analysis. The regression analysis of the subset was performed using two fundamentally different analysis approaches. First, the data analysis was performed using a recently developed extension of the Iterative Method. This approach fits gage outputs as a function of both applied balance loads and bellows pressures while still allowing the application of the iteration scheme that is used with the Iterative Method. Then, for comparison, the axial force was also analyzed using the Non-Iterative Method. This alternate approach directly fits loads as a function of measured gage outputs and bellows pressures and does not require a load iteration. The regression models used by both the extended Iterative and Non-Iterative Method were constructed such that they met a set of widely accepted statistical quality requirements. These requirements lead to reliable regression models and prevent overfitting of data because they ensure that no hidden near-linear dependencies between regression model terms exist and that only statistically significant terms are included. Finally, a comparison of the axial force residuals was performed. Overall, axial force estimates obtained from both methods show excellent agreement as the differences of the standard deviation of the axial force residuals are on the order of 0.001 % of the axial force capacity.

  7. Longitudinal Metagenomic Analysis of Hospital Air Identifies Clinically Relevant Microbes

    PubMed Central

    King, Paula; Pham, Long K.; Waltz, Shannon; Sphar, Dan; Yamamoto, Robert T.; Conrad, Douglas; Taplitz, Randy; Torriani, Francesca

    2016-01-01

    We describe the sampling of sixty-three uncultured hospital air samples collected over a six-month period and analysis using shotgun metagenomic sequencing. Our primary goals were to determine the longitudinal metagenomic variability of this environment, identify and characterize genomes of potential pathogens and determine whether they are atypical to the hospital airborne metagenome. Air samples were collected from eight locations which included patient wards, the main lobby and outside. The resulting DNA libraries produced 972 million sequences representing 51 gigabases. Hierarchical clustering of samples by the most abundant 50 microbial orders generated three major nodes which primarily clustered by type of location. Because the indoor locations were longitudinally consistent, episodic relative increases in microbial genomic signatures related to the opportunistic pathogens Aspergillus, Penicillium and Stenotrophomonas were identified as outliers at specific locations. Further analysis of microbial reads specific for Stenotrophomonas maltophilia indicated homology to a sequenced multi-drug resistant clinical strain and we observed broad sequence coverage of resistance genes. We demonstrate that a shotgun metagenomic sequencing approach can be used to characterize the resistance determinants of pathogen genomes that are uncharacteristic for an otherwise consistent hospital air microbial metagenomic profile. PMID:27482891

  8. Longitudinal Metagenomic Analysis of Hospital Air Identifies Clinically Relevant Microbes.

    PubMed

    King, Paula; Pham, Long K; Waltz, Shannon; Sphar, Dan; Yamamoto, Robert T; Conrad, Douglas; Taplitz, Randy; Torriani, Francesca; Forsyth, R Allyn

    2016-01-01

    We describe the sampling of sixty-three uncultured hospital air samples collected over a six-month period and analysis using shotgun metagenomic sequencing. Our primary goals were to determine the longitudinal metagenomic variability of this environment, identify and characterize genomes of potential pathogens and determine whether they are atypical to the hospital airborne metagenome. Air samples were collected from eight locations which included patient wards, the main lobby and outside. The resulting DNA libraries produced 972 million sequences representing 51 gigabases. Hierarchical clustering of samples by the most abundant 50 microbial orders generated three major nodes which primarily clustered by type of location. Because the indoor locations were longitudinally consistent, episodic relative increases in microbial genomic signatures related to the opportunistic pathogens Aspergillus, Penicillium and Stenotrophomonas were identified as outliers at specific locations. Further analysis of microbial reads specific for Stenotrophomonas maltophilia indicated homology to a sequenced multi-drug resistant clinical strain and we observed broad sequence coverage of resistance genes. We demonstrate that a shotgun metagenomic sequencing approach can be used to characterize the resistance determinants of pathogen genomes that are uncharacteristic for an otherwise consistent hospital air microbial metagenomic profile.

  9. A network-based gene-weighting approach for pathway analysis.

    PubMed

    Fang, Zhaoyuan; Tian, Weidong; Ji, Hongbin

    2012-03-01

    Classical algorithms aiming at identifying biological pathways significantly related to studying conditions frequently reduced pathways to gene sets, with an obvious ignorance of the constitutive non-equivalence of various genes within a defined pathway. We here designed a network-based method to determine such non-equivalence in terms of gene weights. The gene weights determined are biologically consistent and robust to network perturbations. By integrating the gene weights into the classical gene set analysis, with a subsequent correction for the "over-counting" bias associated with multi-subunit proteins, we have developed a novel gene-weighed pathway analysis approach, as implemented in an R package called "Gene Associaqtion Network-based Pathway Analysis" (GANPA). Through analysis of several microarray datasets, including the p53 dataset, asthma dataset and three breast cancer datasets, we demonstrated that our approach is biologically reliable and reproducible, and therefore helpful for microarray data interpretation and hypothesis generation.

  10. Managing the analysis of air quality impacts under NEPA

    SciTech Connect

    Weber, Y.B.; Leslie, A.C.D.

    1995-12-31

    The National Environmental Policy Act of 1969 (NEPA) mandates the analysis and evaluation of potential impacts of major Federal actions having the potential to affect the environment. The Clean Air Act Amendments of 1990 identify an array of new air quality issues appropriate for analysis in compliance with NEPA. An example is emissions of the 189 hazardous air pollutants identified in Title III. The utility industry estimates that more than 2.4 billion pounds of toxic pollutants were emitted to the atmosphere in 1988, with the potential for resultant adverse health impacts such as cancer, reproductive effects, birth defects, and respiratory illness. The US Department of Energy (DOE) provides Federal funds for projects that utilize coal as the primary fuel, including the approximately 45 projects funded over the past ten years under the Clean Coal Technology Demonstration Program. Provision of Federal funds brings these projects under NEPA review. While electric steam generating units greater than 25 MW are currently excluded from regulatory review for the 189 air toxics listed in Title III, they are not, due to their potential impacts, excluded from NEPA review when Federally funded, in whole or in part. The authors will discuss their experiences drawn from NEPA evaluations of coal-fired power projects, the differences between regulatory requirements and NEPA requirements, source categories, major and area sources, conformity, maximum achievable control technology, mandatory licensing, radionuclides, visibility, toxics found to be emitted from coal combustion, public involvement, citizen suits, the bounty system, and how NEPA review can result in beneficial changes to proposed projects through mitigation measures to avoid or minimize potentially adverse environmental impacts.

  11. A systematic analysis of a mi-RNA inter-pathway regulatory motif

    PubMed Central

    2013-01-01

    Background The continuing discovery of new types and functions of small non-coding RNAs is suggesting the presence of regulatory mechanisms far more complex than the ones currently used to study and design Gene Regulatory Networks. Just focusing on the roles of micro RNAs (miRNAs), they have been found to be part of several intra-pathway regulatory motifs. However, inter-pathway regulatory mechanisms have been often neglected and require further investigation. Results In this paper we present the result of a systems biology study aimed at analyzing a high-level inter-pathway regulatory motif called Pathway Protection Loop, not previously described, in which miRNAs seem to play a crucial role in the successful behavior and activation of a pathway. Through the automatic analysis of a large set of public available databases, we found statistical evidence that this inter-pathway regulatory motif is very common in several classes of KEGG Homo Sapiens pathways and concurs in creating a complex regulatory network involving several pathways connected by this specific motif. The role of this motif seems also confirmed by a deeper review of other research activities on selected representative pathways. Conclusions Although previous studies suggested transcriptional regulation mechanism at the pathway level such as the Pathway Protection Loop, a high-level analysis like the one proposed in this paper is still missing. The understanding of higher-level regulatory motifs could, as instance, lead to new approaches in the identification of therapeutic targets because it could unveil new and “indirect” paths to activate or silence a target pathway. However, a lot of work still needs to be done to better uncover this high-level inter-pathway regulation including enlarging the analysis to other small non-coding RNA molecules. PMID:24152805

  12. Analysis of the aspartic acid metabolic pathway using mutant genes.

    PubMed

    Azevedo, R A

    2002-01-01

    Amino acid metabolism is a fundamental process for plant growth and development. Although a considerable amount of information is available, little is known about the genetic control of enzymatic steps or regulation of several pathways. Much of the information about biochemical pathways has arisen from the use of mutants lacking key enzymes. Although mutants were largely used already in the 60's, by bacterial and fungal geneticists, it took plant research a long time to catch up. The advance in this area was rapid in the 80's, which was followed in the 90's by the development of techniques of plant transformation. In this review we present an overview of the aspartic acid metabolic pathway, the key regulatory enzymes and the mutants and transgenic plants produced for lysine and threonine metabolism. We also discuss and propose a new study of high-lysine mutants.

  13. Space-Time Analysis of the Air Quality Model Evaluation International Initiative (AQMEII) Phase 1 Air Quality Simulations

    EPA Science Inventory

    This study presents an evaluation of summertime daily maximum ozone concentrations over North America (NA) and Europe (EU) using the database generated during Phase 1 of the Air Quality Model Evaluation International Initiative (AQMEII). The analysis focuses on identifying tempor...

  14. Conceptual Model for Assessing Criteria Air Pollutants in a Multipollutant Context: A Modified Adverse Outcome Pathway Approach

    EPA Science Inventory

    Background: Air pollution consists of a complex mixture of particulate and gaseous components. Individual criteria and other hazardous air pollutants have been linked to adverse respiratory and cardiovascular health outcomes. However, assessing risk of air pollutant mixtures is d...

  15. Adaptive elastic-net sparse principal component analysis for pathway association testing.

    PubMed

    Chen, Xi

    2011-10-24

    Pathway or gene set analysis has become an increasingly popular approach for analyzing high-throughput biological experiments such as microarray gene expression studies. The purpose of pathway analysis is to identify differentially expressed pathways associated with outcomes. Important challenges in pathway analysis are selecting a subset of genes contributing most to association with clinical phenotypes and conducting statistical tests of association for the pathways efficiently. We propose a two-stage analysis strategy: (1) extract latent variables representing activities within each pathway using a dimension reduction approach based on adaptive elastic-net sparse principal component analysis; (2) integrate the latent variables with the regression modeling framework to analyze studies with different types of outcomes such as binary, continuous or survival outcomes. Our proposed approach is computationally efficient. For each pathway, because the latent variables are estimated in an unsupervised fashion without using disease outcome information, in the sample label permutation testing procedure, the latent variables only need to be calculated once rather than for each permutation resample. Using both simulated and real datasets, we show our approach performed favorably when compared with five other currently available pathway testing methods.

  16. Adaptive Elastic-Net Sparse Principal Component Analysis for Pathway Association Testing

    PubMed Central

    Chen, Xi

    2011-01-01

    Pathway or gene set analysis has become an increasingly popular approach for analyzing high-throughput biological experiments such as microarray gene expression studies. The purpose of pathway analysis is to identify differentially expressed pathways associated with outcomes. Important challenges in pathway analysis are selecting a subset of genes contributing most to association with clinical phenotypes and conducting statistical tests of association for the pathways efficiently. We propose a two-stage analysis strategy: (1) extract latent variables representing activities within each pathway using a dimension reduction approach based on adaptive elastic-net sparse principal component analysis; (2) integrate the latent variables with the regression modeling framework to analyze studies with different types of outcomes such as binary, continuous or survival outcomes. Our proposed approach is computationally efficient. For each pathway, because the latent variables are estimated in an unsupervised fashion without using disease outcome information, in the sample label permutation testing procedure, the latent variables only need to be calculated once rather than for each permutation resample. Using both simulated and real datasets, we show our approach performed favorably when compared with five other currently available pathway testing methods. PMID:23089825

  17. Pathway-Informed Classification System (PICS) for Cancer Analysis Using Gene Expression Data

    PubMed Central

    Young, Michael R; Craft, David L

    2016-01-01

    We introduce Pathway-Informed Classification System (PICS) for classifying cancers based on tumor sample gene expression levels. PICS is a computational method capable of expeditiously elucidating both known and novel biological pathway involvement specific to various cancers and uses that learned pathway information to separate patients into distinct classes. The method clearly separates a pan-cancer dataset by tissue of origin and also sub-classifies individual cancer datasets into distinct survival classes. Gene expression values are collapsed into pathway scores that reveal which biological activities are most useful for clustering cancer cohorts into subtypes. Variants of the method allow it to be used on datasets that do and do not contain noncancerous samples. Activity levels of all types of pathways, broadly grouped into metabolic, cellular processes and signaling, and immune system, are useful for separating the pan-cancer cohort. In the clustering of specific cancer types, certain pathway types become more valuable depending on the site being studied. For lung cancer, signaling pathways dominate; for pancreatic cancer, signaling and metabolic pathways dominate; and for melanoma, immune system pathways are the most useful. This work suggests the utility of pathway-level genomic analysis and points in the direction of using pathway classification for predicting the efficacy and side effects of drugs and radiation. PMID:27486299

  18. Air Force Standard Analysis Toolkit and Analysis Approach

    DTIC Science & Technology

    2005-12-01

    Survivability & Vulnerability Engineering & Engagement Level Analysis •Discrete Events •Engagement-Level •Stochastic Tools • Impact of: Tactics...Survivability & Vulnerability: Impacts on Mission Level Analysis Confederation •Airlift Capability •Tanker Deploy/Employ Requirements •Logistics Flow...Discrete Events •Mission-Level •Stochastic Tools • Impact of: CONOPS Tactics C4ISR Sensors TMD 17I n t e g r i t y - S e r v i c e - E x c e l l e n

  19. Motor current signature analysis: A potential diagnostic for air conditioners

    SciTech Connect

    Miller, W.A.; Haynes, H.D.; Griffin, F.P.; Levins, W.P.; Karnitz, M.A.

    1988-03-01

    Recent advancements in modern electronics have made it possible to collect the various ''transient noise'' signals which are present on electric power lines of motor-driven equipment while using a simple non-intrusive clamp-on inductive pickup. Electronic filters are used to analyze the noise signal with an on-the-spot, real-time analysis. An exploratory study, conducted at ORNL, examined the potential for using the motor current signature on heat pumps and air conditioners as a diagnostic tool. Preliminary results show that there is some correlation between the motor current signature and the performance of a heat pump. However, the tests and associated analysis were limited, and additional research is needed to determine the full potential of motor current signature analysis (MCSA).

  20. Dynamic heave-pitch analysis of air cushion landing systems

    NASA Technical Reports Server (NTRS)

    Captain, K. M.; Boghani, A. B.; Wormley, D. N.

    1975-01-01

    A program to develop analytical tools for evaluating the dynamic performance of Air Cushion Landing Systems (ACLS) is described. The heave (vertical) motion of the ACLS was analyzed, and the analysis was extended to cover coupled heave-pitch motions. The mathematical models developed are based on a fundamental analysis of the body dynamics and fluid mechanics of the aircraft-cushion-runway interaction. The air source characteristics, flow losses in the feeding ducts, trunk and cushion, the effects of fluid compressibility, and dynamic trunk deflections, including ground contact are considered. A computer program, based on the heave-pitch analysis, was developed to simulate the dynamic behavior of an ACLS during landing impact and taxi over an irregular runway. The program outputs include ACLS motions, loadings, pressures, and flows as a function of time. To illustrate program use, three basic types of simulations were carried out. The results provide an initial indication of ACLS performance during (1) a static drop, (2) landing impact, and (3) taxi over a runway irregularity.

  1. The Feasibility of Oil Analysis for Air Force Diesel Engines

    DTIC Science & Technology

    1979-06-01

    period 18 September 1978 to 18 June 1979. The Air F’orce Project Monitor was MrW~ le MaW e, - an rton16h ALC /MMET,’ . Mr. J,P. Cuellar, Jr., of SwRI...insolub les 28 TABLE 5. RELATION OF USED CRANKCASE OIL ANALYSIS TO ENGINE CONDITION OR OPERATION (Cont’d) Contributing Engine Condition Test Result...guidelines for wearmetal and lubricant control limits. 46. Schilling, A. (Chief Engineer, Institut Francais du Petrole ), Automobile Engine Lubrication, 1972

  2. [Analysis of the impact of two typical air pollution events on the air quality of Nanjing].

    PubMed

    Wang, Fei; Zhu, Bin; Kang, Han-Qing; Gao, Jin-Hui; Wang, Yin; Jiang, Qi

    2012-10-01

    Nanjing and the surrounding area have experienced two consecutive serious air pollution events from late October to early November in 2009. The first event was long-lasting haze pollution, and the second event was resulted from the mixed impact of crop residue burning and local transportation. The effects of regional transport and local sources on the two events were discussed by cluster analysis, using surface meteorological observations, air pollution index, satellite remote sensing of fire hot spots data and back trajectory model. The results showed that the accumulation-mode aerosol number concentrations were higher than those of any other aerosol modes in the two pollution processes. The peak value of aerosol particle number concentrations shifted to large particle size compare with the previous studies in this area. The ratio of SO4(2-)/NO3(-) was 1.30 and 0.99, indicating that stationary sources were more important than traffic sources in the first event and the reverse in the second event. Affected by the local sources from east and south, the particle counts below 0.1 microm gradually accumulated in the first event. The second event was mainly affected by a short-distance transport from northeast and local sources from southwest, especially south, the concentration of aerosol particles was higher than those in other directions, indicating that the sources of crop residue burning were mainly in this direction.

  3. Air Force Training: Further Analysis and Planning Needed to Improve Effectiveness

    DTIC Science & Technology

    2016-09-01

    explained that Red Flag exercises require a significant adversary air presence to provide high quality training for the participants. As discussed... AIR FORCE TRAINING Further Analysis and Planning Needed to Improve Effectiveness Report to Congressional Committees...GAO-16-864, a report to congressional committees September 2016 AIR FORCE TRAINING Further Analysis and Planning Needed to Improve

  4. Incorporating principal component analysis into air quality model evaluation

    NASA Astrophysics Data System (ADS)

    Eder, Brian; Bash, Jesse; Foley, Kristen; Pleim, Jon

    2014-01-01

    The efficacy of standard air quality model evaluation techniques is becoming compromised as the simulation periods continue to lengthen in response to ever increasing computing capacity. Accordingly, the purpose of this paper is to demonstrate a statistical approach called Principal Component Analysis (PCA) with the intent of motivating its use by the evaluation community. One of the main objectives of PCA is to identify, through data reduction, the recurring and independent modes of variations (or signals) within a very large dataset, thereby summarizing the essential information of that dataset so that meaningful and descriptive conclusions can be made. In this demonstration, PCA is applied to a simple evaluation metric - the model bias associated with EPA's Community Multi-scale Air Quality (CMAQ) model when compared to weekly observations of sulfate (SO42-) and ammonium (NH4+) ambient air concentrations measured by the Clean Air Status and Trends Network (CASTNet). The advantages of using this technique are demonstrated as it identifies strong and systematic patterns of CMAQ model bias across a myriad of spatial and temporal scales that are neither constrained to geopolitical boundaries nor monthly/seasonal time periods (a limitation of many current studies). The technique also identifies locations (station-grid cell pairs) that are used as indicators for a more thorough diagnostic evaluation thereby hastening and facilitating understanding of the probable mechanisms responsible for the unique behavior among bias regimes. A sampling of results indicates that biases are still prevalent in both SO42- and NH4+ simulations that can be attributed to either: 1) cloud processes in the meteorological model utilized by CMAQ, which are found to overestimated convective clouds and precipitation, while underestimating larger-scale resolved clouds that are less likely to precipitate, and 2) biases associated with Midwest NH3 emissions which may be partially ameliorated

  5. Candidate pathway based analysis for cleft lip with or without cleft palate.

    PubMed

    Zhang, Tian-Xiao; Beaty, Terri H; Ruczinski, Ingo

    2012-01-06

    The objective of this research was to identify potential biological pathways associated with non-syndromic cleft lip with or without cleft palate (NSCL/P), and to explore the potential biological mechanisms underlying these associated pathways on risk of NSCL/P. This project was based on the dataset of a previously published genome-wide association (GWA) study on NSCL/P (Beaty et al. 2010). Case-parent trios used here originated from an international consortium (The Gene, Environment Association Studies consortium, GENEVA) formed in 2007. A total of 5,742 individuals from 1,908 CL/P case-parents trios (1,591 complete trios and 317 incomplete trios where one parent was missing) were collected and genotyped using the Illumina Human610-Quad array. Candidate pathways were selected using a list of 356 genes that may be related to oral clefts. In total, 42 candidate pathways, which included 1,564 genes and 40,208 SNPs were tested. Using a pathway-based analysis approach proposed by Wang et al (2007), we conducted a permutation-based test to assess the statistical significance of the nominal p-values of 42 candidate pathways. The analysis revealed several pathways yielding nominally significant p-values. However, controlling for the family wise error rate, none of these pathways could retain statistical significance. Nominal p-values of these pathways were concentrated at the lower tail of the distribution, with more than expected low p-values. A permutation based test for examining this type of distribution pattern yielded an overall p-value of 0.029. Thus, while this pathway-based analysis did not yield a clear significant result for any particular pathway, we conclude that one or more of the genes and pathways considered here likely do play a role in oral clefting.

  6. Comparative Analysis of Protein Glycosylation Pathways in Humans and the Fungal Pathogen Candida albicans

    PubMed Central

    Martínez-Duncker, Iván; Díaz-Jímenez, Diana F.; Mora-Montes, Héctor M.

    2014-01-01

    Protein glycosylation pathways are present in all kingdoms of life and are metabolic pathways found in all the life kingdoms. Despite sharing commonalities in their synthesis, glycans attached to glycoproteins have species-specific structures generated by the presence of different sets of enzymes and acceptor substrates in each organism. In this review, we present a comparative analysis of the main glycosylation pathways shared by humans and the fungal pathogen Candida albicans: N-linked glycosylation, O-linked mannosylation and glycosylphosphatidylinositol-anchorage. The knowledge of similarities and divergences between these metabolic pathways could help find new pharmacological targets for C. albicans infection. PMID:25104959

  7. The pathway of in-situ ammonium removal from aerated municipal solid waste bioreactor: nitrification/denitrification or air stripping?

    PubMed

    Hao, Yong-Jun; Ji, Min; Chen, Ying-Xu; Wu, Wei-Xiang; Hao, Yong-Jun; Zhang, Shu-Guang; Liu, Han-Qiao

    2010-12-01

    In-situ ammonium removal from municipal solid waste (MSW) landfill is an attractive method due to its economic advantages. In this study, two simulated MSW bioreactors with different degrees of initial bio-stabilization were utilized to investigate the effects of intermittent aeration mode and the addition of activated sludge on the removal of ammonium. The results showed that up to 90% of ammonium could be removed and the amount of NO(x)-N produced was less than 1% of NH4 (+)-N removed in both reactors. The pH values increased rapidly and finally arrived at a high level of 8.5-8.8. The efficiency of ammonium removal was improved by increasing the continuous aeration time, but it was not affected by the addition of activated sludge. A portion of liquid escaped from the reactors in the form of vapour, and as high as 195-258 mg L(-1) of NH(4) ( +)-N was detected in the vapour collector. According to calculation, nitrification was inhibited by the high level of free ammonia in the bioreactors. As a result, air stripping was enhanced and became the primary pathway of ammonium removal. Therefore, controlling free ammonia concentration was essential in ammonium removal from the aerated MSW bioreactor.

  8. Application of a prospective model for calculating worker exposure due to the air pathway for operations in a laboratory.

    PubMed

    Grimbergen, T W M; Wiegman, M M

    2007-01-01

    In order to arrive at recommendations for guidelines on maximum allowable quantities of radioactive material in laboratories, a proposed mathematical model was used for the calculation of transfer fractions for the air pathway. A set of incident scenarios was defined, including spilling, leakage and failure of the fume hood. For these 'common incidents', dose constraints of 1 mSv and 0.1 mSv are proposed in case the operations are being performed in a controlled area and supervised area, respectively. In addition, a dose constraint of 1 microSv is proposed for each operation under regular working conditions. Combining these dose constraints and the transfer fractions calculated with the proposed model, maximum allowable quantities were calculated for different laboratory operations and situations. Provided that the calculated transfer fractions can be experimentally validated and the dose constraints are acceptable, it can be concluded from the results that the dose constraint for incidents is the most restrictive one. For non-volatile materials this approach leads to quantities much larger than commonly accepted. In those cases, the results of the calculations in this study suggest that limitation of the quantity of radioactive material, which can be handled safely, should be based on other considerations than the inhalation risks. Examples of such considerations might be the level of external exposure, uncontrolled spread of radioactive material by surface contamination, emissions in the environment and severe accidents like fire.

  9. PerPAS: Topology-Based Single Sample Pathway Analysis Method.

    PubMed

    Liu, Chengyu; Lehtonen, Rainer; Hautaniemi, Sampsa

    2017-03-08

    Identification of intracellular pathways that play key roles in cancer progression and drug resistance is a prerequisite for developing targeted cancer treatments. The era of personalized medicine calls for computational methods that can function with one sample or very small set of samples. Developing such methods is challenging because standard statistical approaches pose several limiting assumptions, such as number of samples, that prevent their application when n approaches to one. We have developed a novel pathway analysis method called PerPAS to estimate pathway activity at a single sample level by integrating pathway topology and transcriptomics data. In addition, PerPAS is able to identify altered pathways between cancer and control samples as well as to identify key nodes that contribute to the pathway activity. In our case study using breast cancer data, we show that PerPAS can identify highly altered pathways that are associated with patient survival. PerPAS identified four pathways that were associated with patient survival and were successfully validated in three independent breast cancer cohorts. In comparison to two other pathway analysis methods that function at a single sample level, PerPAS had superior performance in both synthetic and breast cancer expression datasets. PerPAS is a free R package (http://csbi.ltdk.helsinki.fi/pub/czliu/perpas/).

  10. Design and analysis of synthetic carbon fixation pathways

    PubMed Central

    Bar-Even, Arren; Noor, Elad; Lewis, Nathan E.; Milo, Ron

    2010-01-01

    Carbon fixation is the process by which CO2 is incorporated into organic compounds. In modern agriculture in which water, light, and nutrients can be abundant, carbon fixation could become a significant growth-limiting factor. Hence, increasing the fixation rate is of major importance in the road toward sustainability in food and energy production. There have been recent attempts to improve the rate and specificity of Rubisco, the carboxylating enzyme operating in the Calvin–Benson cycle; however, they have achieved only limited success. Nature employs several alternative carbon fixation pathways, which prompted us to ask whether more efficient novel synthetic cycles could be devised. Using the entire repertoire of approximately 5,000 metabolic enzymes known to occur in nature, we computationally identified alternative carbon fixation pathways that combine existing metabolic building blocks from various organisms. We compared the natural and synthetic pathways based on physicochemical criteria that include kinetics, energetics, and topology. Our study suggests that some of the proposed synthetic pathways could have significant quantitative advantages over their natural counterparts, such as the overall kinetic rate. One such cycle, which is predicted to be two to three times faster than the Calvin–Benson cycle, employs the most effective carboxylating enzyme, phosphoenolpyruvate carboxylase, using the core of the naturally evolved C4 cycle. Although implementing such alternative cycles presents daunting challenges related to expression levels, activity, stability, localization, and regulation, we believe our findings suggest exciting avenues of exploration in the grand challenge of enhancing food and renewable fuel production via metabolic engineering and synthetic biology. PMID:20410460

  11. Distribution pathways of hexachlorocyclohexane isomers in a soil-plant-air system. A case study with Cynara scolymus L. and Erica sp. plants grown in a contaminated site.

    PubMed

    Pereira, R Calvelo; Monterroso, C; Macías, F; Camps-Arbestain, M

    2008-09-01

    This study focuses on the main routes of distribution and accumulation of different hexachlorocyclohexane (HCH) isomers (mainly alpha-, beta-, gamma- and delta-HCH) in a soil-plant-air system. A field assay was carried out with two plant species, Cynara scolymus L. and Erica sp., which were planted either: (i) directly in the HCH-contaminated soil; or (ii) in pots filled with uncontaminated soil, which were placed in the HCH-contaminated soil. Both plant species accumulated HCH in their tissues, with relatively higher accumulation in above-ground biomass than in roots. The beta-HCH isomer was the main isomer in all plant tissues. Adsorption of HCH by the roots from contaminated soil (soil-->root pathway) and adsorption through the aerial biomass from either the surrounding air, following volatilization of the contaminant (soil-->air-->shoot pathway), and/or contact with air-suspended particles contaminated with HCH (soil particles-->shoot pathway) were the main mechanisms of accumulation. These results may have important implications for the use of plants for reducing the transfer of contaminants via the atmosphere.

  12. Dynamic biochemical reaction process analysis and pathway modification predictions.

    PubMed

    Conejeros, R; Vassiliadis, V S

    2000-05-05

    Recently, the area of model predictive modification of biochemical pathways has received attention with the aim to increase the productivity of microbial systems. In this study, we present a generalization of previous work, where, using a sensitivity study over the fermentation as a dynamic system, the optimal selection of reaction steps for modification (amplification or attenuation) is determined. The influence of metabolites in the activity of enzymes has also been considered (through activation or inhibition). We further introduce a new concept in the dynamic modeling of biochemical reaction systems including a generalized continuous superstructure in which two artificial multiplicative terms are included to account for: (a) enzyme overexpression or underexpression (attenuation or amplification) for the whole enzyme pool; and (b) modification of the apparent order of a kinetic expression with respect to the concentration of a metabolite or any subset of metabolites participating in the pathway. This new formulation allows the prediction of the sensitivity of the pathway performance index (objective function) with respect to the concentration of the enzyme, as well as the interaction of the enzyme with other metabolites. Using this framework, a case study for the production of penicillin V is analyzed, obtaining the most sensitive reaction steps (or bottlenecks) and the most significant regulations of the system, due to the effect of concentration of intracellular metabolites on the activity of each enzyme.

  13. Analysis of air quality management with emphasis on transportation sources

    NASA Technical Reports Server (NTRS)

    English, T. D.; Divita, E.; Lees, L.

    1980-01-01

    The current environment and practices of air quality management were examined for three regions: Denver, Phoenix, and the South Coast Air Basin of California. These regions were chosen because the majority of their air pollution emissions are related to mobile sources. The impact of auto exhaust on the air quality management process is characterized and assessed. An examination of the uncertainties in air pollutant measurements, emission inventories, meteorological parameters, atmospheric chemistry, and air quality simulation models is performed. The implications of these uncertainties to current air quality management practices is discussed. A set of corrective actions are recommended to reduce these uncertainties.

  14. Review of metabolic pathways activated in cancer cells as determined through isotopic labeling and network analysis.

    PubMed

    Dong, Wentao; Keibler, Mark A; Stephanopoulos, Gregory

    2017-02-10

    Cancer metabolism has emerged as an indispensable part of contemporary cancer research. During the past 10 years, the use of stable isotopic tracers and network analysis have unveiled a number of metabolic pathways activated in cancer cells. Here, we review such pathways along with the particular tracers and labeling observations that led to the discovery of their rewiring in cancer cells. The list of such pathways comprises the reductive metabolism of glutamine, altered glycolysis, serine and glycine metabolism, mutant isocitrate dehydrogenase (IDH) induced reprogramming and the onset of acetate metabolism. Additionally, we demonstrate the critical role of isotopic labeling and network analysis in identifying these pathways. The alterations described in this review do not constitute a complete list, and future research using these powerful tools is likely to discover other cancer-related pathways and new metabolic targets for cancer therapy.

  15. Analysis of Air Flow in the Ventilated Insulating Air Layer of the External Wall

    NASA Astrophysics Data System (ADS)

    Katunská, Jana; Bullová, Iveta; Špaková, Miroslava

    2016-12-01

    The paper deals with problems of impact of air flow in ventilated insulating air layer of the external wall on behaviour of thermal-technical parameters of the proposed external structure (according principles of STN 73 0549, which is not valid now), by comparing them in the calculation according to the valid STN standards, where air flow in the ventilated air layer is not taken into account, as well as by comparing them with behavior of thermal-technical parameters in the proposal of sandwich external wall with the contact heat insulation system without air cavity.

  16. A Growing Role for Gender Analysis in Air Pollution Epidemiology

    PubMed Central

    Clougherty, Jane E.

    2010-01-01

    Objective Epidemiologic studies of air pollution effects on respiratory health report significant modification by sex, although results are not uniform. Importantly, it remains unclear whether modifications are attributable to socially derived gendered exposures, to sex-linked physiological differences, or to some interplay thereof. Gender analysis, which aims to disaggregate social from biological differences between males and females, may help to elucidate these possible sources of effect modification. Data sources and data extraction A PubMed literature search was performed in July 2009, using the terms “respiratory” and any of “sex” or “gender” or “men and women” or “boys and girls” and either “PM2.5” (particulate matter ≥ 2.5 μm in aerodynamic diameter) or “NO2” (nitrogen dioxide). I reviewed the identified studies, and others cited therein, to summarize current evidence of effect modification, with attention to authors’ interpretation of observed differences. Owing to broad differences in exposure mixes, outcomes, and analytic techniques, with few studies examining any given combination thereof, meta-analysis was not deemed appropriate at this time. Data synthesis More studies of adults report stronger effects among women, particularly for older persons or where using residential exposure assessment. Studies of children suggest stronger effects among boys in early life and among girls in later childhood. Conclusions The qualitative review describes possible sources of difference in air pollution response between women and men, which may vary by life stage, coexposures, hormonal status, or other factors. The sources of observed effect modifications remain unclear, although gender analytic approaches may help to disentangle gender and sex differences in pollution response. A framework for incorporating gender analysis into environmental epidemiology is offered, along with several potentially useful methods from gender analysis

  17. An Integrated Safety Analysis Methodology for Emerging Air Transport Technologies

    NASA Technical Reports Server (NTRS)

    Kostiuk, Peter F.; Adams, Milton B.; Allinger, Deborah F.; Rosch, Gene; Kuchar, James

    1998-01-01

    The continuing growth of air traffic will place demands on NASA's Air Traffic Management (ATM) system that cannot be accommodated without the creation of significant delays and economic impacts. To deal with this situation, work has begun to develop new approaches to providing a safe and economical air transportation infrastructure. Many of these emerging air transport technologies will represent radically new approaches to ATM, both for ground and air operations.

  18. Critical Radionuclide and Pathway Analysis for the Savannah River Site, 2016 Update

    SciTech Connect

    Jannik, Tim; Hartman, Larry

    2016-09-08

    During the operational history of Savannah River Site, many different radionuclides have been released from site facilities. However, as shown in this analysis, only a relatively small number of the released radionuclides have been significant contributors to doses to the offsite public. This report is an update to the 2011 analysis, Critical Radionuclide and Pathway Analysis for the Savannah River Site. SRS-based Performance Assessments for E-Area, Saltstone, F-Tank Farm, H-Tank Farm, and a Comprehensive SRS Composite Analysis have been completed. The critical radionuclides and pathways identified in those extensive reports are also detailed and included in this analysis.

  19. Proteomic Analysis of Hylocereus polyrhizus Reveals Metabolic Pathway Changes

    PubMed Central

    Hua, Qingzhu; Zhou, Qianjun; Gan, Susheng; Wu, Jingyu; Chen, Canbin; Li, Jiaqiang; Ye, Yaoxiong; Zhao, Jietang; Hu, Guibing; Qin, Yonghua

    2016-01-01

    Red dragon fruit or red pitaya (Hylocereus polyrhizus) is the only edible fruit that contains betalains. The color of betalains ranges from red and violet to yellow in plants. Betalains may also serve as an important component of health-promoting and disease-preventing functional food. Currently, the biosynthetic and regulatory pathways for betalain production remain to be fully deciphered. In this study, isobaric tags for relative and absolute quantitation (iTRAQ)-based proteomic analyses were used to reveal the molecular mechanism of betalain biosynthesis in H. polyrhizus fruits at white and red pulp stages, respectively. A total of 1946 proteins were identified as the differentially expressed between the two samples, and 936 of them were significantly highly expressed at the red pulp stage of H. polyrhizus. RNA-seq and iTRAQ analyses showed that some transcripts and proteins were positively correlated; they belonged to “phenylpropanoid biosynthesis”, “tyrosine metabolism”, “flavonoid biosynthesis”, “ascorbate and aldarate metabolism”, “betalains biosynthesis” and “anthocyanin biosynthesis”. In betalains biosynthesis pathway, several proteins/enzymes such as polyphenol oxidase, CYP76AD3 and 4,5-dihydroxy-phenylalanine (DOPA) dioxygenase extradiol-like protein were identified. The present study provides a new insight into the molecular mechanism of the betalain biosynthesis at the posttranscriptional level. PMID:27690004

  20. Integrative analysis of cancer-related signaling pathways.

    PubMed

    Kessler, Thomas; Hache, Hendrik; Wierling, Christoph

    2013-01-01

    Identification and classification of cancer types and subtypes is a major issue in current cancer research. Whole genome expression profiling of cancer tissues is often the basis for such subtype classifications of tumors and different signatures for individual cancer types have been described. However, the search for best performing discriminatory gene-expression signatures covering more than one cancer type remains a relevant topic in cancer research as such a signature would help understanding the common changes in signaling networks in these disease types. In this work, we explore the idea of a top down approach for sample stratification based on a module-based network of cancer relevant signaling pathways. For assembly of this network, we consider several of the most established cancer pathways. We evaluate our sample stratification approach using expression data of human breast and ovarian cancer signatures. We show that our approach performs equally well to previously reported methods besides providing the advantage to classify different cancer types. Furthermore, it allows to identify common changes in network module activity of those cancer samples.

  1. Proteomic Analysis of Hylocereus polyrhizus Reveals Metabolic Pathway Changes.

    PubMed

    Hua, Qingzhu; Zhou, Qianjun; Gan, Susheng; Wu, Jingyu; Chen, Canbin; Li, Jiaqiang; Ye, Yaoxiong; Zhao, Jietang; Hu, Guibing; Qin, Yonghua

    2016-09-28

    Red dragon fruit or red pitaya (Hylocereus polyrhizus) is the only edible fruit that contains betalains. The color of betalains ranges from red and violet to yellow in plants. Betalains may also serve as an important component of health-promoting and disease-preventing functional food. Currently, the biosynthetic and regulatory pathways for betalain production remain to be fully deciphered. In this study, isobaric tags for relative and absolute quantitation (iTRAQ)-based proteomic analyses were used to reveal the molecular mechanism of betalain biosynthesis in H. polyrhizus fruits at white and red pulp stages, respectively. A total of 1946 proteins were identified as the differentially expressed between the two samples, and 936 of them were significantly highly expressed at the red pulp stage of H. polyrhizus. RNA-seq and iTRAQ analyses showed that some transcripts and proteins were positively correlated; they belonged to "phenylpropanoid biosynthesis", "tyrosine metabolism", "flavonoid biosynthesis", "ascorbate and aldarate metabolism", "betalains biosynthesis" and "anthocyanin biosynthesis". In betalains biosynthesis pathway, several proteins/enzymes such as polyphenol oxidase, CYP76AD3 and 4,5-dihydroxy-phenylalanine (DOPA) dioxygenase extradiol-like protein were identified. The present study provides a new insight into the molecular mechanism of the betalain biosynthesis at the posttranscriptional level.

  2. Identification of hub genes and pathways associated with retinoblastoma based on co-expression network analysis.

    PubMed

    Wang, Q L; Chen, X; Zhang, M H; Shen, Q H; Qin, Z M

    2015-12-08

    The objective of this paper was to identify hub genes and pathways associated with retinoblastoma using centrality analysis of the co-expression network and pathway-enrichment analysis. The co-expression network of retinoblastoma was constructed by weighted gene co-expression network analysis (WGCNA) based on differentially expressed (DE) genes, and clusters were obtained through the molecular complex detection (MCODE) algorithm. Degree centrality analysis of the co-expression network was performed to explore hub genes present in retinoblastoma. Pathway-enrichment analysis was performed using the Kyoto Encyclopedia of Genes and Genomes (KEGG) database. Validation of hub gene expression in retinoblastoma was performed by reverse transcription-polymerase chain reaction (RT-PCR) analysis. The co-expression network based on 221 DE genes between retinoblastoma and normal controls consisted of 210 nodes and 3965 edges, and 5 clusters of the network were evaluated. By assessing the centrality analysis of the co-expression network, 21 hub genes were identified, such as SNORD115-41, RASSF2, and SNORD115-44. According to RT-PCR analysis, 16 of the 21 hub genes were differently expressed, including RASSF2 and CDCA7, and 5 were not differently expressed in retinoblastoma compared to normal controls. Pathway analysis showed that genes in 2 clusters were enriched in 3 pathways: purine metabolism, p53 signaling pathway, and melanogenesis. In this study, we successfully identified 16 hub genes and 3 pathways associated with retinoblastoma, which may be potential biomarkers for early detection and therapy for retinoblastoma.

  3. Tissue Non-Specific Genes and Pathways Associated with Diabetes: An Expression Meta-Analysis.

    PubMed

    Mei, Hao; Li, Lianna; Liu, Shijian; Jiang, Fan; Griswold, Michael; Mosley, Thomas

    2017-01-21

    We performed expression studies to identify tissue non-specific genes and pathways of diabetes by meta-analysis. We searched curated datasets of the Gene Expression Omnibus (GEO) database and identified 13 and five expression studies of diabetes and insulin responses at various tissues, respectively. We tested differential gene expression by empirical Bayes-based linear method and investigated gene set expression association by knowledge-based enrichment analysis. Meta-analysis by different methods was applied to identify tissue non-specific genes and gene sets. We also proposed pathway mapping analysis to infer functions of the identified gene sets, and correlation and independent analysis to evaluate expression association profile of genes and gene sets between studies and tissues. Our analysis showed that PGRMC1 and HADH genes were significant over diabetes studies, while IRS1 and MPST genes were significant over insulin response studies, and joint analysis showed that HADH and MPST genes were significant over all combined data sets. The pathway analysis identified six significant gene sets over all studies. The KEGG pathway mapping indicated that the significant gene sets are related to diabetes pathogenesis. The results also presented that 12.8% and 59.0% pairwise studies had significantly correlated expression association for genes and gene sets, respectively; moreover, 12.8% pairwise studies had independent expression association for genes, but no studies were observed significantly different for expression association of gene sets. Our analysis indicated that there are both tissue specific and non-specific genes and pathways associated with diabetes pathogenesis. Compared to the gene expression, pathway association tends to be tissue non-specific, and a common pathway influencing diabetes development is activated through different genes at different tissues.

  4. Tissue Non-Specific Genes and Pathways Associated with Diabetes: An Expression Meta-Analysis

    PubMed Central

    Mei, Hao; Li, Lianna; Liu, Shijian; Jiang, Fan; Griswold, Michael; Mosley, Thomas

    2017-01-01

    We performed expression studies to identify tissue non-specific genes and pathways of diabetes by meta-analysis. We searched curated datasets of the Gene Expression Omnibus (GEO) database and identified 13 and five expression studies of diabetes and insulin responses at various tissues, respectively. We tested differential gene expression by empirical Bayes-based linear method and investigated gene set expression association by knowledge-based enrichment analysis. Meta-analysis by different methods was applied to identify tissue non-specific genes and gene sets. We also proposed pathway mapping analysis to infer functions of the identified gene sets, and correlation and independent analysis to evaluate expression association profile of genes and gene sets between studies and tissues. Our analysis showed that PGRMC1 and HADH genes were significant over diabetes studies, while IRS1 and MPST genes were significant over insulin response studies, and joint analysis showed that HADH and MPST genes were significant over all combined data sets. The pathway analysis identified six significant gene sets over all studies. The KEGG pathway mapping indicated that the significant gene sets are related to diabetes pathogenesis. The results also presented that 12.8% and 59.0% pairwise studies had significantly correlated expression association for genes and gene sets, respectively; moreover, 12.8% pairwise studies had independent expression association for genes, but no studies were observed significantly different for expression association of gene sets. Our analysis indicated that there are both tissue specific and non-specific genes and pathways associated with diabetes pathogenesis. Compared to the gene expression, pathway association tends to be tissue non-specific, and a common pathway influencing diabetes development is activated through different genes at different tissues. PMID:28117714

  5. A hypothesis-driven pathway analysis reveals myelin-related pathways that contribute to the risk of schizophrenia and bipolar disorder.

    PubMed

    Yu, Hao; Bi, Wenjian; Liu, Chenxing; Zhao, Yanlong; Zhang, Dai; Yue, Weihua

    2014-06-03

    Schizophrenia (SZ) and bipolar disorder (BD) are both severe neuropsychiatric disorders with a strong and potential overlapping genetic background. Multiple lines of evidence, including genetic studies, gene expression studies and neuroimaging studies, have suggested that both disorders are closely related to myelin and oligodendrocyte dysfunctions. In the current study, we hypothesized that the holistic effect of the myelin-related pathway contributes to the genetic susceptibility to both SZ and BD. We extracted pathway data from the canonical pathway database, Gene Ontology (GO), and selected a 'compiled' pathway based on previous literature. We then performed hypothesis-driven pathway analysis on GWAS data from the Psychiatric Genomics Consortium (PGC). As a result, we identified three myelin-related pathways with a joint effect significantly associated with both disorders: 'Myelin sheath' pathway (P(SZ) = 2.45E-7, P(BD) = 1.22E-3), 'Myelination' pathway (P(SZ) = 2.10E-4, P(BD) = 2.53E-24), and 'Compiled' pathway (P(SZ) = 4.57E-8, P(BD) = 2.61E-9). In comparing the SNPs and genes in these three pathways across the two diseases, we identified a substantial overlap in nominally associated SNPs and genes, which could be susceptibility SNPs and genes for both disorders. From these observations, we propose that myelin-related pathways may be involved in the etiologies of both SZ and BD.

  6. Thermal analysis of Perforated Metal Air Transportable Package (PMATP) prototype.

    SciTech Connect

    Oneto, Robert; Levine, Howard; Mould, John; Pierce, Jim Dwight

    2003-08-01

    Sandia National Laboratories (SNL) has designed a crash-resistant container, the Perforated Metal Air Transportable Package (PMATP), capable of surviving a worst-case plane crash, including both impact and subsequent fire, for the air transport of plutonium. This report presents thermal analyses of the full-scale PMATP in its undamaged (pre-test) condition and in bounding post-accident states. The goal of these thermal simulations was to evaluate the performance of the package in a worst-case post-crash fire. The full-scale package is approximately 1.6 m long by 0.8 m diameter. The thermal analyses were performed with the FLEX finite element code. This analysis clearly predicts that the PMATP provides acceptable thermal response characteristics, both for the post-accident fire of a one-hour duration and the after-fire heat-soak condition. All predicted temperatures for the primary containment vessel are well within design limits for safety.

  7. Heart-rate monitoring by air pressure and causal analysis

    NASA Astrophysics Data System (ADS)

    Tsuchiya, Naoki; Nakajima, Hiroshi; Hata, Yutaka

    2011-06-01

    Among lots of vital signals, heart-rate (HR) is an important index for diagnose human's health condition. For instance, HR provides an early stage of cardiac disease, autonomic nerve behavior, and so forth. However, currently, HR is measured only in medical checkups and clinical diagnosis during the rested state by using electrocardiograph (ECG). Thus, some serious cardiac events in daily life could be lost. Therefore, a continuous HR monitoring during 24 hours is desired. Considering the use in daily life, the monitoring should be noninvasive and low intrusive. Thus, in this paper, an HR monitoring in sleep by using air pressure sensors is proposed. The HR monitoring is realized by employing the causal analysis among air pressure and HR. The causality is described by employing fuzzy logic. According to the experiment on 7 males at age 22-25 (23 on average), the correlation coefficient against ECG is 0.73-0.97 (0.85 on average). In addition, the cause-effect structure for HR monitoring is arranged by employing causal decomposition, and the arranged causality is applied to HR monitoring in a setting posture. According to the additional experiment on 6 males, the correlation coefficient is 0.66-0.86 (0.76 on average). Therefore, the proposed method is suggested to have enough accuracy and robustness for some daily use cases.

  8. An objective isobaric/isentropic technique for upper air analysis

    NASA Technical Reports Server (NTRS)

    Mancuso, R. L.; Endlich, R. M.; Ehernberger, L. J.

    1981-01-01

    An objective meteorological analysis technique is presented whereby both horizontal and vertical upper air analyses are performed. The process used to interpolate grid-point values from the upper-air station data is the same as for grid points on both an isobaric surface and a vertical cross-sectional plane. The nearby data surrounding each grid point are used in the interpolation by means of an anisotropic weighting scheme, which is described. The interpolation for a grid-point potential temperature is performed isobarically; whereas wind, mixing-ratio, and pressure height values are interpolated from data that lie on the isentropic surface that passes through the grid point. Two versions (A and B) of the technique are evaluated by qualitatively comparing computer analyses with subjective handdrawn analyses. The objective products of version A generally have fair correspondence with the subjective analyses and with the station data, and depicted the structure of the upper fronts, tropopauses, and jet streams fairly well. The version B objective products correspond more closely to the subjective analyses, and show the same strong gradients across the upper front with only minor smoothing.

  9. Bayesian analysis of a reduced-form air quality model.

    PubMed

    Foley, Kristen M; Reich, Brian J; Napelenok, Sergey L

    2012-07-17

    Numerical air quality models are being used for assessing emission control strategies for improving ambient pollution levels across the globe. This paper applies probabilistic modeling to evaluate the effectiveness of emission reduction scenarios aimed at lowering ground-level ozone concentrations. A Bayesian hierarchical model is used to combine air quality model output and monitoring data in order to characterize the impact of emissions reductions while accounting for different degrees of uncertainty in the modeled emissions inputs. The probabilistic model predictions are weighted based on population density in order to better quantify the societal benefits/disbenefits of four hypothetical emission reduction scenarios in which domain-wide NO(x) emissions from various sectors are reduced individually and then simultaneously. Cross validation analysis shows the statistical model performs well compared to observed ozone levels. Accounting for the variability and uncertainty in the emissions and atmospheric systems being modeled is shown to impact how emission reduction scenarios would be ranked, compared to standard methodology.

  10. In silico Pathway Activation Network Decomposition Analysis (iPANDA) as a method for biomarker development

    PubMed Central

    Ozerov, Ivan V.; Lezhnina, Ksenia V.; Izumchenko, Evgeny; Artemov, Artem V.; Medintsev, Sergey; Vanhaelen, Quentin; Aliper, Alexander; Vijg, Jan; Osipov, Andreyan N.; Labat, Ivan; West, Michael D.; Buzdin, Anton; Cantor, Charles R.; Nikolsky, Yuri; Borisov, Nikolay; Irincheeva, Irina; Khokhlovich, Edward; Sidransky, David; Camargo, Miguel Luiz; Zhavoronkov, Alex

    2016-01-01

    Signalling pathway activation analysis is a powerful approach for extracting biologically relevant features from large-scale transcriptomic and proteomic data. However, modern pathway-based methods often fail to provide stable pathway signatures of a specific phenotype or reliable disease biomarkers. In the present study, we introduce the in silico Pathway Activation Network Decomposition Analysis (iPANDA) as a scalable robust method for biomarker identification using gene expression data. The iPANDA method combines precalculated gene coexpression data with gene importance factors based on the degree of differential gene expression and pathway topology decomposition for obtaining pathway activation scores. Using Microarray Analysis Quality Control (MAQC) data sets and pretreatment data on Taxol-based neoadjuvant breast cancer therapy from multiple sources, we demonstrate that iPANDA provides significant noise reduction in transcriptomic data and identifies highly robust sets of biologically relevant pathway signatures. We successfully apply iPANDA for stratifying breast cancer patients according to their sensitivity to neoadjuvant therapy. PMID:27848968

  11. EXPath: a database of comparative expression analysis inferring metabolic pathways for plants

    PubMed Central

    2015-01-01

    Background In general, the expression of gene alters conditionally to catalyze a specific metabolic pathway. Microarray-based datasets have been massively produced to monitor gene expression levels in parallel with numerous experimental treatments. Although several studies facilitated the linkage of gene expression data and metabolic pathways, none of them are amassed for plants. Moreover, advanced analysis such as pathways enrichment or how genes express under different conditions is not rendered. Description Therefore, EXPath was developed to not only comprehensively congregate the public microarray expression data from over 1000 samples in biotic stress, abiotic stress, and hormone secretion but also allow the usage of this abundant resource for coexpression analysis and differentially expression genes (DEGs) identification, finally inferring the enriched KEGG pathways and gene ontology (GO) terms of three model plants: Arabidopsis thaliana, Oryza sativa, and Zea mays. Users can access the gene expression patterns of interest under various conditions via five main functions (Gene Search, Pathway Search, DEGs Search, Pathways/GO Enrichment, and Coexpression analysis) in EXPath, which are presented by a user-friendly interface and valuable for further research. Conclusions In conclusion, EXPath, freely available at http://expath.itps.ncku.edu.tw, is a database resource that collects and utilizes gene expression profiles derived from microarray platforms under various conditions to infer metabolic pathways for plants. PMID:25708775

  12. Similarity measure between patient traces for clinical pathway analysis: problem, method, and applications.

    PubMed

    Huang, Zhengxing; Dong, Wei; Duan, Huilong; Li, Haomin

    2014-01-01

    Clinical pathways leave traces, described as event sequences with regard to a mixture of various latent treatment behaviors. Measuring similarities between patient traces can profitably be exploited further as a basis for providing insights into the pathways, and complementing existing techniques of clinical pathway analysis (CPA), which mainly focus on looking at aggregated data seen from an external perspective. Most existing methods measure similarities between patient traces via computing the relative distance between their event sequences. However, clinical pathways, as typical human-centered processes, always take place in an unstructured fashion, i.e., clinical events occur arbitrarily without a particular order. Bringing order in the chaos of clinical pathways may decline the accuracy of similarity measure between patient traces, and may distort the efficiency of further analysis tasks. In this paper, we present a behavioral topic analysis approach to measure similarities between patient traces. More specifically, a probabilistic graphical model, i.e., latent Dirichlet allocation (LDA), is employed to discover latent treatment behaviors of patient traces for clinical pathways such that similarities of pairwise patient traces can be measured based on their underlying behavioral topical features. The presented method provides a basis for further applications in CPA. In particular, three possible applications are introduced in this paper, i.e., patient trace retrieval, clustering, and anomaly detection. The proposed approach and the presented applications are evaluated via a real-world dataset of several specific clinical pathways collected from a Chinese hospital.

  13. An Image Based System Biology Approach for Alzheimer's Disease Pathway Analysis.

    PubMed

    Huang, Yue; Zhou, Xiaobo; Miao, Benchun; Lipinski, Marta; Xia, Zheng; Hu, Guangshu; Degterev, Alexei; Yuan, Junying; Wong, Stephen T C

    2009-04-01

    We report multifactorial analysis of candidate mechanisms of Alzheimer's disease utilizing high content analysis, gene expression microarray, and linear regression model to integrate neuronal imaging data with hippocampal gene expression data. Our analysis led to the identification of several genes that may contribute to different image traits or phenotypes in the amyloid-beta (Aβ) injured neurons. Gene network and biological pathways analysis for those genes were further analyzed and led to several novel pathways that may contribute to amyloid plaque triggered neurite loss.

  14. Interlaboratory analysis of high molecular weight organochlorines in ambient air

    NASA Astrophysics Data System (ADS)

    Bidleman, Terry F.

    High volume air samples were collected in Boston, MA, and Columbia, SC using a glass fiber filter — polyurethane foam trap, and the pooled sample extracts from each location were distributed among nine laboratories for organochlorine analysis. Polychlorinated biphenyls (PCB) were reported by all laboratories, with relative standard deviations (RSDs) ranging from 26-39 % for total PCB. The total PCB concentration in Boston was 7.1 ng m -3, compared to 4.4 ng m -3 in Columbia. Other organochlorines identified by three or more laboratories included hexachlorobenzene and the pesticides DDT, DDE, chlordane, dieldrin, endrin, hexachlorocyclohexane, and polychloroterpenes. RSDs for most pesticides ranged from 35-75% and as high as 116% for polychloroterpenes (quantified as toxaphene). In general, pesticide levels were an order of magnitude higher in Columbia than in Boston.

  15. Genetic analysis of photoreceptor action pathways in Arabidopsis thaliana

    SciTech Connect

    Not Available

    1991-01-01

    The specific strategies and long-term goals of this proposal remain intact relative to the original proposal. We continue to isolate and characterize photomorphogenic mutants of Arabidopsis thaliana. The molecular and biochemical characterization of one of these mutants, det1, has led to one publication of original data and to one Society for Experimental Biology Symposium paper (see below). The phenotype of a second mutant, det2, has also been studied during this funding period. In addition, we have continued work on a general strategy to isolate mutations in trans-acting regulatory factors that mediate light-regulated gene expression, and have identified several potentially interesting regulatory mutants. In the third funding period, we will concentrate on the genetical, biochemical, and molecular characterization of these new mutants. Construction of double mutants between the new mutants and the previously characterized morphological mutants should allow us to construct a pathway for light-regulated seedling development in Arabidopsis.

  16. Meta-Analysis of Gene Expression Profiles in Acute Promyelocytic Leukemia Reveals Involved Pathways

    PubMed Central

    Jalili, Mahdi; Salehzadeh-Yazdi, Ali; Mohammadi, Saeed; Yaghmaie, Marjan; Ghavamzadeh, Ardeshir; Alimoghaddam, Kamran

    2017-01-01

    Background: Acute promyelocytic leukemia (APL) is a unique subtype of acute leukemia. APL is a curable disease; however, drug resistance, early mortality, disease relapse and treatment-related complications remain challenges in APL patient management. One issue underlying these challenges is that the molecular mechanisms of the disease are not sufficiently understood. Materials and Methods: In this study, we performed a meta-analysis of gene expression profiles derived from microarray experiments and explored the background of disease by functional and pathway analysis. Results: Our analysis revealed a gene signature with 406 genes that are up or down-regulated in APL. The pathway analysis determined that MAPK pathway and its involved elements such as JUN gene and AP-1 play important roles in APL pathogenesis along with insulin-like growth factor–binding protein-7. Conclusion: The results of this meta-analysis could be useful for developing more effective therapy strategies and new targets for diagnosis and drugs. PMID:28286608

  17. BACT analysis under the Clean Air Act's PCD program

    SciTech Connect

    Simms, P.; Walke, J.

    2006-11-15

    Before a company may build a new major industrial source of air pollution, or make modifications to an existing major source in the USA it must apply for and receive a Clean Air Act (CAA) Prevention of Significant Deterioration (PSD) permit. State environmental agencies typically issue such permits, either under state law or by exercising delegated authority to implement the federal PSD program. To fully comply with the CAA, the emissions limits identified as BACT must incorporate consideration of more than just add-on emissions control technology, they must also reflect appropriate considerations of fuel quality (e.g. low-sulfur coal) and process changes (e.g. advanced combustion techniques) as a means of controlling emissions, and must consider the other environmental and public welfare benefits of the identified emissions control options. Several states including New Mexico and Illinois have already determined that innovated technologies, such as Integrated Gasification Combined Cycle (IGCC), must be considered in connection with the BACT analysis for new coal-fired power plants. Even the notion that BACT is categorically limited in scope to the general type of facility proposed is contrary to EPA precedent. For example, the Environmental Appeals Board (EAB) has explained that permitting authorities retain the discretion under the definition of BACT to require dramatically different facility designs (e.g. a natural gas plant instead of a coal-fired power plant). The best advice for any permit applicant is to include in the BACT analysis a careful and honest examination of better performing alternative processes and/or innovative combustion techniques and to aggressively pursue such options wherever feasible. 17 refs.

  18. Rapid Analysis, Self-Calibrating Array for Air Monitoring

    NASA Technical Reports Server (NTRS)

    Homer, Margie L.; Shevade, Abhijit V.; Lara, Liana; Huerta, Ramon; Vergara, Alexander; Muezzinoglua, Mehmet K.

    2012-01-01

    Human space missions have critical needs for monitoring and control for life support systems. These systems have monitoring needs that include feedback for closed loop processes and quality control for environmental factors. Sensors and monitoring technologies assure that the air environment and water supply for the astronaut crew habitat fall within acceptable limits, and that the life support system is functioning properly and efficiently. The longer the flight duration and the more distant the destination, the more critical it becomes to have carefully monitored and automated control systems for life support. Past experiments with the JPL ENose have demonstrated a lifetime of the sensor array, with the software, of around 18 months. The lifetime of the calibration, for some analytes, was as long as 24 months. We are working on a sensor array and new algorithms that will include sensor response time in the analysis. The preliminary array analysis for two analytes shows that the analysis time, of an event, can be dropped from 45 minutes to less than10 minutes and array training time can be cut substantially. We will describe the lifetime testing of an array and show lifetime data on individual sensors. This progress will lead to more rapid identification of analytes, and faster training time of the array.

  19. Stratospheric Air Sub-sampler (SAS) and its application to analysis of Δ17O(CO2) from small air samples collected with an AirCore

    NASA Astrophysics Data System (ADS)

    Janina Mrozek, Dorota; van der Veen, Carina; Hofmann, Magdalena E. G.; Chen, Huilin; Kivi, Rigel; Heikkinen, Pauli; Röckmann, Thomas

    2016-11-01

    We present the set-up and a scientific application of the Stratospheric Air Sub-sampler (SAS), a device to collect and to store the vertical profile of air collected with an AirCore (Karion et al., 2010) in numerous sub-samples for later analysis in the laboratory. The SAS described here is a 20 m long 1/4 inch stainless steel tubing that is separated by eleven valves to divide the tubing into 10 identical segments, but it can be easily adapted to collect smaller or larger samples. In the collection phase the SAS is directly connected to the outlet of an optical analyzer that measures the mole fractions of CO2, CH4 and CO from an AirCore sampler. The stratospheric part (or if desired any part of the AirCore air) is then directed through the SAS. When the SAS is filled with the selected air, the valves are closed and the vertical profile is maintained in the different segments of the SAS. The segments can later be analysed to retrieve vertical profiles of other trace gas signatures that require slower instrumentation. As an application, we describe the coupling of the SAS to an analytical system to determine the 17O excess of CO2, which is a tracer for photochemical processing of stratospheric air. For this purpose the analytical system described by Mrozek et al. (2015) was adapted for analysis of air directly from the SAS. The performance of the coupled system is demonstrated for a set of air samples from an AirCore flight in November 2014 near Sodankylä, Finland. The standard error for a 25 mL air sample at stratospheric CO2 mole fraction is 0.56 ‰ (1σ) for δ17O and 0.03 ‰ (1σ) for both δ18O and δ13C. Measured Δ17O(CO2) values show a clear correlation with N2O in agreement with already published data.

  20. Systematic analysis of microarray datasets to identify Parkinson's disease-associated pathways and genes

    PubMed Central

    Feng, Yinling; Wang, Xuefeng

    2017-01-01

    In order to investigate commonly disturbed genes and pathways in various brain regions of patients with Parkinson's disease (PD), microarray datasets from previous studies were collected and systematically analyzed. Different normalization methods were applied to microarray datasets from different platforms. A strategy combining gene co-expression networks and clinical information was adopted, using weighted gene co-expression network analysis (WGCNA) to screen for commonly disturbed genes in different brain regions of patients with PD. Functional enrichment analysis of commonly disturbed genes was performed using the Database for Annotation, Visualization, and Integrated Discovery (DAVID). Co-pathway relationships were identified with Pearson's correlation coefficient tests and a hypergeometric distribution-based test. Common genes in pathway pairs were selected out and regarded as risk genes. A total of 17 microarray datasets from 7 platforms were retained for further analysis. Five gene coexpression modules were identified, containing 9,745, 736, 233, 101 and 93 genes, respectively. One module was significantly correlated with PD samples and thus the 736 genes it contained were considered to be candidate PD-associated genes. Functional enrichment analysis demonstrated that these genes were implicated in oxidative phosphorylation and PD. A total of 44 pathway pairs and 52 risk genes were revealed, and a risk gene pathway relationship network was constructed. Eight modules were identified and were revealed to be associated with PD, cancers and metabolism. A number of disturbed pathways and risk genes were unveiled in PD, and these findings may help advance understanding of PD pathogenesis. PMID:28098893

  1. Genome wide analysis of transcript levels after perturbation of the EGFR pathway in the Drosophila ovary.

    PubMed

    Jordan, Katherine C; Hatfield, Steven D; Tworoger, Michael; Ward, Ellen J; Fischer, Karin A; Bowers, Stuart; Ruohola-Baker, Hannele

    2005-03-01

    Defects in the epidermal growth factor receptor (EGFR) pathway can lead to aggressive tumor formation. Activation of this pathway during normal development produces multiple outcomes at the cellular level, leading to cellular differentiation and cell cycle activation. To elucidate the downstream events induced by this pathway, we used genome-wide cDNA microarray technology to identify potential EGFR targets in Drosophila oogenesis. We focused on genes for which the transcriptional responses due to EGFR pathway activation and inactivation were in opposite directions, as this is expected for genes that are directly regulated by the pathway in this tissue type. We perturbed the EGFR pathway in epithelial follicle cells using seven different genetic backgrounds. To activate the pathway, we overexpressed an activated form of the EGFR (UAS-caEGFR), and an activated form of the signal transducer Raf (UAS-caRaf); we also over- or ectopically expressed the downstream homeobox transcription factor Mirror (UAS-mirr) and the ligand-activating serine protease Rhomboid (UAS-rho). To reduce pathway activity we used loss-of-function mutations in the ligand (gurken) and receptor (torpedo). From microarrays containing 6,255 genes, we found 454 genes that responded in an opposite manner in gain-of-function and loss-of-function conditions among which are many Wingless signaling pathway components. Further analysis of two such components, sugarless and pangolin, revealed a function for these genes in late follicle cell patterning. Of interest, components of other signaling pathways were also enriched in the EGFR target group, suggesting that one reason for the pleiotropic effects seen with EGFR activity in cancer progression and development may be its ability to regulate many other signaling pathways.

  2. DEVELOPMENT AND ANALYSIS OF AIR QUALITY MODELING SIMULATIONS FOR HAZARDOUS AIR POLLUTANTS

    EPA Science Inventory

    The concentrations of five hazardous air pollutants were simulated using the Community Multi Scale Air Quality (CMAQ) modeling system. Annual simulations were performed over the continental United States for the entire year of 2001 to support human exposure estimates. Results a...

  3. Transcriptome analysis in tardigrade species reveals specific molecular pathways for stress adaptations.

    PubMed

    Förster, Frank; Beisser, Daniela; Grohme, Markus A; Liang, Chunguang; Mali, Brahim; Siegl, Alexander Matthias; Engelmann, Julia C; Shkumatov, Alexander V; Schokraie, Elham; Müller, Tobias; Schnölzer, Martina; Schill, Ralph O; Frohme, Marcus; Dandekar, Thomas

    2012-01-01

    Tardigrades have unique stress-adaptations that allow them to survive extremes of cold, heat, radiation and vacuum. To study this, encoded protein clusters and pathways from an ongoing transcriptome study on the tardigrade Milnesium tardigradum were analyzed using bioinformatics tools and compared to expressed sequence tags (ESTs) from Hypsibius dujardini, revealing major pathways involved in resistance against extreme environmental conditions. ESTs are available on the Tardigrade Workbench along with software and databank updates. Our analysis reveals that RNA stability motifs for M. tardigradum are different from typical motifs known from higher animals. M. tardigradum and H. dujardini protein clusters and conserved domains imply metabolic storage pathways for glycogen, glycolipids and specific secondary metabolism as well as stress response pathways (including heat shock proteins, bmh2, and specific repair pathways). Redox-, DNA-, stress- and protein protection pathways complement specific repair capabilities to achieve the strong robustness of M. tardigradum. These pathways are partly conserved in other animals and their manipulation could boost stress adaptation even in human cells. However, the unique combination of resistance and repair pathways make tardigrades and M. tardigradum in particular so highly stress resistant.

  4. Transcriptome Analysis in Tardigrade Species Reveals Specific Molecular Pathways for Stress Adaptations

    PubMed Central

    Förster, Frank; Beisser, Daniela; Grohme, Markus A.; Liang, Chunguang; Mali, Brahim; Siegl, Alexander Matthias; Engelmann, Julia C.; Shkumatov, Alexander V.; Schokraie, Elham; Müller, Tobias; Schnölzer, Martina; Schill, Ralph O.; Frohme, Marcus; Dandekar, Thomas

    2012-01-01

    Tardigrades have unique stress-adaptations that allow them to survive extremes of cold, heat, radiation and vacuum. To study this, encoded protein clusters and pathways from an ongoing transcriptome study on the tardigrade Milnesium tardigradum were analyzed using bioinformatics tools and compared to expressed sequence tags (ESTs) from Hypsibius dujardini, revealing major pathways involved in resistance against extreme environmental conditions. ESTs are available on the Tardigrade Workbench along with software and databank updates. Our analysis reveals that RNA stability motifs for M. tardigradum are different from typical motifs known from higher animals. M. tardigradum and H. dujardini protein clusters and conserved domains imply metabolic storage pathways for glycogen, glycolipids and specific secondary metabolism as well as stress response pathways (including heat shock proteins, bmh2, and specific repair pathways). Redox-, DNA-, stress- and protein protection pathways complement specific repair capabilities to achieve the strong robustness of M. tardigradum. These pathways are partly conserved in other animals and their manipulation could boost stress adaptation even in human cells. However, the unique combination of resistance and repair pathways make tardigrades and M. tardigradum in particular so highly stress resistant. PMID:22563243

  5. Brucella Melitensis 16M Regulates the Effect of AIR Domain on Inflammatory Factors, Autophagy, and Apoptosis in Mouse Macrophage through the ROS Signaling Pathway

    PubMed Central

    Li, Tiansen; Xu, Yafang; Liu, Laizhen; Huang, Meiling; Wang, Zhen; Tong, Zhixia; Zhang, Hui; Guo, Fei; Chen, Chuangfu

    2016-01-01

    Brucellosis is a highly contagious zoonosis caused by Brucella. Brucella can invade and persist inside host cells, which results in chronic infection. We constructed AIR interference and overexpression lentiviruses to acquire AIR interference, overexpression, and rescue stable expression cell lines. We also established a Brucella melitensis 16M-infected macrophage model, which was treated with either the vehicle control or NAC (ROS scavenger N-acetylcysteine (NAC) for 0, 3, 6, 12, and 24 h. Confocal laser microscopy, transmission electron microscopy, fluorescence quantitative PCR, flow cytometry, ELISA, and Western blot were used to detect inflammation, cell autophagy and apoptosis-related protein expression levels, ROS levels, and the distribution of mitochondria. It was found that after interference and overexpression of AIR, ROS release was significantly changed, and mitochondria became abnormally aggregated. B. melitensis 16M activated the NLRP3/AIM2 inflammatory complex, and induced RAW264.7 cells to secrete IL-1β and IL-18 through the ROS pathway. B. melitensis 16M also altered autophagy-related gene expression, increased autophagy activity, and induced cell apoptosis through the ROS pathway. The results showed that after B. melitensis 16M infection, ROS induced apoptosis, inflammation, and autophagy while AIR inhibited autophagosome maturation and autophagy initiation. Autophagy negatively regulated the activation of inflammasomes and prevented inflammation from occurring. In addition, mitophagy could promote cell apoptosis. PMID:27907115

  6. Metabolomic analysis reveals altered metabolic pathways in a rat model of gastric carcinogenesis

    PubMed Central

    Gu, Jinping; Hu, Xiaomin; Shao, Wei; Ji, Tianhai; Yang, Wensheng; Zhuo, Huiqin; Jin, Zeyu; Huang, Huiying; Chen, Jiacheng; Huang, Caihua; Lin, Donghai

    2016-01-01

    Gastric cancer (GC) is one of the most malignant tumors with a poor prognosis. Alterations in metabolic pathways are inextricably linked to GC progression. However, the underlying molecular mechanisms remain elusive. We performed NMR-based metabolomic analysis of sera derived from a rat model of gastric carcinogenesis, revealed significantly altered metabolic pathways correlated with the progression of gastric carcinogenesis. Rats were histologically classified into four pathological groups (gastritis, GS; low-grade gastric dysplasia, LGD; high-grade gastric dysplasia, HGD; GC) and the normal control group (CON). The metabolic profiles of the five groups were clearly distinguished from each other. Furthermore, significant inter-metabolite correlations were extracted and used to reconstruct perturbed metabolic networks associated with the four pathological stages compared with the normal stage. Then, significantly altered metabolic pathways were identified by pathway analysis. Our results showed that oxidative stress-related metabolic pathways, choline phosphorylation and fatty acid degradation were continually disturbed during gastric carcinogenesis. Moreover, amino acid metabolism was perturbed dramatically in gastric dysplasia and GC. The GC stage showed more changed metabolite levels and more altered metabolic pathways. Two activated pathways (glycolysis; glycine, serine and threonine metabolism) substantially contributed to the metabolic alterations in GC. These results lay the basis for addressing the molecular mechanisms underlying gastric carcinogenesis and extend our understanding of GC progression. PMID:27527852

  7. Control of asthma triggers in indoor air with air cleaners: a modeling analysis

    PubMed Central

    Myatt, Theodore A; Minegishi, Taeko; Allen, Joseph G; MacIntosh, David L

    2008-01-01

    Background Reducing exposure to environmental agents indoors shown to increase asthma symptoms or lead to asthma exacerbations is an important component of a strategy to manage asthma for individuals. Numerous investigations have demonstrated that portable air cleaning devices can reduce concentrations of asthma triggers in indoor air; however, their benefits for breathing problems have not always been reproducible. The potential exposure benefits of whole house high efficiency in-duct air cleaners for sensitive subpopulations have yet to be evaluated. Methods We used an indoor air quality modeling system (CONTAM) developed by NIST to examine peak and time-integrated concentrations of common asthma triggers present in indoor air over a year as a function of natural ventilation, portable air cleaners, and forced air ventilation equipped with conventional and high efficiency filtration systems. Emission rates for asthma triggers were based on experimental studies published in the scientific literature. Results Forced air systems with high efficiency filtration were found to provide the best control of asthma triggers: 30–55% lower cat allergen levels, 90–99% lower risk of respiratory infection through the inhalation route of exposure, 90–98% lower environmental tobacco smoke (ETS) levels, and 50–75% lower fungal spore levels than the other ventilation/filtration systems considered. These results indicate that the use of high efficiency in-duct air cleaners provide an effective means of controlling allergen levels not only in a single room, like a portable air cleaner, but the whole house. Conclusion These findings are useful for evaluating potential benefits of high efficiency in-duct filtration systems for controlling exposure to asthma triggers indoors and for the design of trials of environmental interventions intended to evaluate their utility in practice. PMID:18684328

  8. Effect of clinical nursing pathway for endoscopic thyroidectomy in Chinese patients: A meta-analysis.

    PubMed

    Yang, Yu; Hu, Xinhua; Zhang, Qiang; Cao, Hui; Li, Jun; Wang, Junpeng; Shao, Yang; Xin, Shijie

    2016-06-01

    The aim of this study was to assess the effect of the use of a clinical nursing pathway for patients undergoing endoscopic thyroidectomy by conducting a meta-analysis. Electronic databases were searched for relevant controlled trials published prior to August 2013. Only papers that compared the use of a clinical nursing pathway to usual care for patients undergoing endoscopic thyroidectomy were selected. The outcome measures were mean difference and 95% confidence interval for length of hospital stay and hospital charges and risk ratio for patient satisfaction. Six controlled trials were identified. The use of a clinical nursing pathway reduced the length of hospital stay and hospital charges. Furthermore, it improved patient satisfaction. This meta-analysis indicates that application of a clinical nursing pathway appears to reduce length of hospital stay and hospital charges and improve patient satisfaction for patients undergoing endoscopic thyroidectomy.

  9. Tools for the analysis of metabolic flux through the sphingolipid pathway.

    PubMed

    Martínez-Montañés, Fernando; Schneiter, Roger

    2016-11-01

    Discerning the complex regulation of the enzymatic steps necessary for sphingolipid biosynthesis is facilitated by the utilization of tracers that allow a time-resolved analysis of the pathway dynamics without affecting the metabolic flux. Different strategies have been used and new tools are continuously being developed to probe the various enzymatic conversions that occur within this complex pathway. Here, we provide a short overview of the divergent fungal and mammalian sphingolipid biosynthetic routes, and of the tracers and methods that are frequently employed to follow the flux of intermediates throughout these pathways.

  10. Development of a clinical pathways analysis system with adaptive Bayesian nets and data mining techniques.

    PubMed

    Kopec, D; Shagas, G; Reinharth, D; Tamang, S

    2004-01-01

    The use and development of software in the medical field offers tremendous opportunities for making health care delivery more efficient, more effective, and less error-prone. We discuss and explore the use of clinical pathways analysis with Adaptive Bayesian Networks and Data Mining Techniques to perform such analyses. The computation of "lift" (a measure of completed pathways improvement potential) leads us to optimism regarding the potential for this approach.

  11. Systems Level Analysis and Identification of Pathways and Networks Associated with Liver Fibrosis

    DTIC Science & Technology

    2014-11-07

    Systems Level Analysis and Identification of Pathways and Networks Associated with Liver Fibrosis Mohamed Diwan M. AbdulHameed1, Gregory J. Tawa1...Toxic liver injury causes necrosis and fibrosis, which may lead to cirrhosis and liver failure. Despite recent progress in understanding the...mechanism of liver fibrosis, our knowledge of the molecular-level details of this disease is still incomplete. The elucidation of networks and pathways

  12. Cathodic degradation of antibiotics: characterization and pathway analysis.

    PubMed

    Kong, Deyong; Liang, Bin; Yun, Hui; Cheng, Haoyi; Ma, Jincai; Cui, Minhua; Wang, Aijie; Ren, Nanqi

    2015-04-01

    Antibiotics in wastewaters must be degraded to eliminate their antibacterial activity before discharging into the environment. A cathode can provide continuous electrons for the degradation of refractory pollutants, however the cathodic degradation feasibility, efficiency and pathway for different kinds of antibiotics is poorly understood. Here, we investigated the degradation of four antibiotics, namely nitrofurazone (NFZ), metronidazole (MNZ), chloramphenicol (CAP), and florfenicol (FLO) by a poised cathode in a dual chamber electrochemical reactor. The cyclic voltammetry preliminarily proved the feasibility of the cathodic degradation of these antibiotics. The cathodic reducibility of these antibiotics followed the order of NFZ > MNZ > CAP > FLO. A decreased phosphate buffered solution (PBS) concentration as low as 2 mM or utilization of NaCl buffer solution as catholyte had significant influence on antibiotics degradation rate and efficiency for CAP and FLO but not for NFZ and MNZ. PBS could be replaced by Na2CO3-NaHCO3 buffer solution as catholyte for the degradation of these antibiotics. Reductive dechlorination of CAP proceeded only after the reduction of the nitro group to aromatic amine. The composition of the degradation products depended on the cathode potential except for MNZ. The cathodic degradation process could eliminate the antibacterial activity of these antibiotics. The current study suggests that the electrochemical reduction could serve as a potential pretreatment or advanced treatment unit for the treatment of antibiotics containing wastewaters.

  13. Ambient Air Pollution and Preeclampsia: A Spatiotemporal Analysis

    PubMed Central

    Figueras, Francesc; Basagaña, Xavier; Beelen, Rob; Martinez, David; Cirach, Marta; Schembari, Anna; Hoek, Gerard; Brunekreef, Bert; Nieuwenhuijsen, Mark J

    2013-01-01

    topic. Citation: Dadvand P, Figueras F, Basagaña X, Beelen R, Martinez D, Cirach M, Schembari A, Hoek G, Brunekreef B, Nieuwenhuijsen MJ. 2013. Ambient air pollution and preeclampsia: a spatiotemporal analysis. Environ Health Perspect 121:1365–1371; http://dx.doi.org/10.1289/ehp.1206430 PMID:24021707

  14. Integrative analysis of ocular complications in atherosclerosis unveils pathway convergence and crosstalk.

    PubMed

    Gupta, Akanksha; Mohanty, Pallavi; Bhatnagar, Sonika

    2015-04-01

    Atherosclerosis is a life-threatening disease and a major cause of mortalities worldwide. While many of the atherosclerotic sequelae are reflected as microvascular effects in the eye, the molecular mechanisms of their development is not yet known. In this study, we employed a systems biology approach to unveil the most significant events and key molecular mediators of ophthalmic sequelae caused by atherosclerosis. Literature mining was used to identify the proteins involved in both atherosclerosis and ophthalmic diseases. A protein-protein interaction (PPI) network was prepared using the literature-mined seed nodes. Network topological analysis was carried out using Cytoscape, while network nodes were annotated using database for annotation, visualization and integrated discovery in order to identify the most enriched pathways and processes. Network analysis revealed that mitogen-activated protein kinase 1 (MAPK1) and protein kinase C occur with highest betweenness centrality, degree and closeness centrality, thus reflecting their functional importance to the network. Our analysis shows that atherosclerosis-associated ophthalmic complications are caused by the convergence of neurotrophin signaling pathways, multiple immune response pathways and focal adhesion pathway on the MAPK signaling pathway. The PPI network shares features with vasoregression, a process underlying multiple vascular eye diseases. Our study presents a first clear and composite picture of the components and crosstalk of the main pathways of atherosclerosis-induced ocular diseases. The hub bottleneck nodes highlight the presence of molecules important for mediating the ophthalmic complications of atherosclerosis and contain five established drug targets for future therapeutic modulation efforts.

  15. Preliminary analysis of hub and spoke air freight distribution system

    NASA Technical Reports Server (NTRS)

    Whitehead, A. H., Jr.

    1978-01-01

    A brief analysis is made of the hub and spoke air freight distribution system which would employ less than 15 hub centers world wide with very large advanced distributed-load freighters providing the line-haul delivery between hubs. This system is compared to a more conventional network using conventionally-designed long-haul freighters which travel between numerous major airports. The analysis calculates all of the transportation costs, including handling charges and pickup and delivery costs. The results show that the economics of the hub/spoke system are severely compromised by the extensive use of feeder aircraft to deliver cargo into and from the large freighter terminals. Not only are the higher costs for the smaller feeder airplanes disadvantageous, but their use implies an additional exchange of cargo between modes compared to truck delivery. The conventional system uses far fewer feeder airplanes, and in many cases, none at all. When feeder aircraft are eliminated from the hub/spoke system, however, that system is universally more economical than any conventional system employing smaller line-haul aircraft.

  16. Spatial analysis of the tuberculosis treatment dropout, Buenos Aires, Argentina.

    PubMed

    Herrero, María Belén; Arrossi, Silvina; Ramos, Silvina; Braga, Jose Ueleres

    2015-01-01

    OBJECTIVE Identify spatial distribution patterns of the proportion of nonadherence to tuberculosis treatment and its associated factors. METHODS We conducted an ecological study based on secondary and primary data from municipalities of the metropolitan area of Buenos Aires, Argentina. An exploratory analysis of the characteristics of the area and the distributions of the cases included in the sample (proportion of nonadherence) was also carried out along with a multifactor analysis by linear regression. The variables related to the characteristics of the population, residences and families were analyzed. RESULTS Areas with higher proportion of the population without social security benefits (p = 0.007) and of households with unsatisfied basic needs had a higher risk of nonadherence (p = 0.032). In addition, the proportion of nonadherence was higher in areas with the highest proportion of households with no public transportation within 300 meters (p = 0.070). CONCLUSIONS We found a risk area for the nonadherence to treatment characterized by a population living in poverty, with precarious jobs and difficult access to public transportation.

  17. Spatial analysis of the tuberculosis treatment dropout, Buenos Aires, Argentina

    PubMed Central

    Herrero, María Belén; Arrossi, Silvina; Ramos, Silvina; Braga, Jose Ueleres

    2015-01-01

    OBJECTIVE Identify spatial distribution patterns of the proportion of nonadherence to tuberculosis treatment and its associated factors. METHODS We conducted an ecological study based on secondary and primary data from municipalities of the metropolitan area of Buenos Aires, Argentina. An exploratory analysis of the characteristics of the area and the distributions of the cases included in the sample (proportion of nonadherence) was also carried out along with a multifactor analysis by linear regression. The variables related to the characteristics of the population, residences and families were analyzed. RESULTS Areas with higher proportion of the population without social security benefits (p = 0.007) and of households with unsatisfied basic needs had a higher risk of nonadherence (p = 0.032). In addition, the proportion of nonadherence was higher in areas with the highest proportion of households with no public transportation within 300 meters (p = 0.070). CONCLUSIONS We found a risk area for the nonadherence to treatment characterized by a population living in poverty, with precarious jobs and difficult access to public transportation. PMID:26270011

  18. Green pathways: Metabolic network analysis of plant systems.

    PubMed

    Dersch, Lisa Maria; Beckers, Veronique; Wittmann, Christoph

    2016-03-01

    Metabolic engineering of plants with enhanced crop yield and value-added compositional traits is particularly challenging as they probably exhibit the highest metabolic network complexity of all living organisms. Therefore, approaches of plant metabolic network analysis, which can provide systems-level understanding of plant physiology, appear valuable as guidance for plant metabolic engineers. Strongly supported by the sequencing of plant genomes, a number of different experimental and computational methods have emerged in recent years to study plant systems at various levels: from heterotrophic cell cultures to autotrophic entire plants. The present review presents a state-of-the-art toolbox for plant metabolic network analysis. Among the described approaches are different in silico modeling techniques, including flux balance analysis, elementary flux mode analysis and kinetic flux profiling, as well as different variants of experiments with plant systems which use radioactive and stable isotopes to determine in vivo plant metabolic fluxes. The fundamental principles of these techniques, the required data input and the obtained flux information are enriched by technical advices, specific to plants. In addition, pioneering and high-impacting findings of plant metabolic network analysis highlight the potential of the field.

  19. Pathway analysis using random forests with bivariate node-split for survival outcomes

    PubMed Central

    Pang, Herbert; Datta, Debayan; Zhao, Hongyu

    2010-01-01

    Motivation: There is great interest in pathway-based methods for genomics data analysis in the research community. Although machine learning methods, such as random forests, have been developed to correlate survival outcomes with a set of genes, no study has assessed the abilities of these methods in incorporating pathway information for analyzing microarray data. In general, genes that are identified without incorporating biological knowledge are more difficult to interpret. Correlating pathway-based gene expression with survival outcomes may lead to biologically more meaningful prognosis biomarkers. Thus, a comprehensive study on how these methods perform in a pathway-based setting is warranted. Results: In this article, we describe a pathway-based method using random forests to correlate gene expression data with survival outcomes and introduce a novel bivariate node-splitting random survival forests. The proposed method allows researchers to identify important pathways for predicting patient prognosis and time to disease progression, and discover important genes within those pathways. We compared different implementations of random forests with different split criteria and found that bivariate node-splitting random survival forests with log-rank test is among the best. We also performed simulation studies that showed random forests outperforms several other machine learning algorithms and has comparable results with a newly developed component-wise Cox boosting model. Thus, pathway-based survival analysis using machine learning tools represents a promising approach in dissecting pathways and for generating new biological hypothesis from microarray studies. Availability: R package Pwayrfsurvival is available from URL: http://www.duke.edu/∼hp44/pwayrfsurvival.htm Contact: pathwayrf@gmail.com Supplementary information: Supplementary data are available at Bioinformatics online. PMID:19933158

  20. Multidimensional scaling analysis of simulated air combat maneuvering performance data.

    PubMed

    Polzella, D J; Reid, G B

    1989-02-01

    This paper describes the decomposition of air combat maneuvering by means of multidimensional scaling (MDS). MDS analyses were applied to performance data obtained from expert and novice pilots during simulated air-to-air combat. The results of these analyses revealed that the performance of expert pilots is characterized by advantageous maneuverability and intelligent energy management. It is argued that MDS, unlike simpler metrics, permits the investigator to achieve greater insights into the underlying structure associated with performance of a complex task.

  1. KEGG-PATH: Kyoto encyclopedia of genes and genomes-based pathway analysis using a path analysis model.

    PubMed

    Du, Junli; Yuan, Zhifa; Ma, Ziwei; Song, Jiuzhou; Xie, Xiaoli; Chen, Yulin

    2014-07-29

    The dynamic impact approach (DIA) represents an alternative to overrepresentation analysis (ORA) for functional analysis of time-course experiments or those involving multiple treatments. The DIA can be used to estimate the biological impact of the differentially expressed genes (DEGs) associated with particular biological functions, for example, as represented by the Kyoto encyclopedia of genes and genomes (KEGG) annotations. However, the DIA does not take into account the correlated dependence structure of the KEGG pathway hierarchy. We have developed herein a path analysis model (KEGG-PATH) to subdivide the total effect of each KEGG pathway into the direct effect and indirect effect by taking into account not only each KEGG pathway itself, but also the correlation with its related pathways. In addition, this work also attempts to preliminarily estimate the impact direction of each KEGG pathway by a gradient analysis method from principal component analysis (PCA). As a result, the advantage of the KEGG-PATH model is demonstrated through the functional analysis of the bovine mammary transcriptome during lactation.

  2. ReactomeFIViz: a Cytoscape app for pathway and network-based data analysis.

    PubMed

    Wu, Guanming; Dawson, Eric; Duong, Adrian; Haw, Robin; Stein, Lincoln

    2014-01-01

    High-throughput experiments are routinely performed in modern biological studies. However, extracting meaningful results from massive experimental data sets is a challenging task for biologists. Projecting data onto pathway and network contexts is a powerful way to unravel patterns embedded in seemingly scattered large data sets and assist knowledge discovery related to cancer and other complex diseases. We have developed a Cytoscape app called "ReactomeFIViz", which utilizes a highly reliable gene functional interaction network combined with human curated pathways derived from Reactome and other pathway databases. This app provides a suite of features to assist biologists in performing pathway- and network-based data analysis in a biologically intuitive and user-friendly way. Biologists can use this app to uncover network and pathway patterns related to their studies, search for gene signatures from gene expression data sets, reveal pathways significantly enriched by genes in a list, and integrate multiple genomic data types into a pathway context using probabilistic graphical models. We believe our app will give researchers substantial power to analyze intrinsically noisy high-throughput experimental data to find biologically relevant information.

  3. Integrated analysis of the miRNA, gene and pathway regulatory network in gastric cancer.

    PubMed

    Zhang, Haiyang; Qu, Yanjun; Duan, Jingjing; Deng, Ting; Liu, Rui; Zhang, Le; Bai, Ming; Li, Jialu; Zhou, Likun; Ning, Tao; Li, Hongli; Ge, Shaohua; Li, Hua; Ying, Guoguang; Huang, Dingzhi; Ba, Yi

    2016-02-01

    Gastric cancer is one of the most common malignant tumors worldwide; however, the efficacy of clinical treatment is limited. MicroRNAs (miRNAs) are a class of small non-coding RNAs that have been reported to play a key role in the development of cancer. They also provide novel candidates for targeted therapy. To date, in-depth studies on the molecular mechanisms of gastric cancer involving miRNAs are still absent. We previously reported that 5 miRNAs were identified as being significantly increased in gastric cancer, and the role of these miRNAs was investigated in the present study. By using bioinformatics tools, we found that more than 4,000 unique genes are potential downstream targets of gastric cancer miRNAs, and these targets belong to the protein class of nucleic acid binding, transcription factor, enzyme modulator, transferase and receptor. Pathway mapping showed that the targets of gastric cancer miRNAs are involved in the MAPK signaling pathway, pathways in cancer, the PI3K-Akt signaling pathway, the HTLV-1 signaling pathway and Ras signaling pathway, thus regulating cell growth, differentiation, apoptosis and metastasis. Analysis of the pathways related to miRNAs may provides potential drug targets for future therapy of gastric cancer.

  4. Personalized Analysis by Validation of Monte Carlo for Application of Pathways in Cardioembolic Stroke.

    PubMed

    Xing, Zhangmin; Luan, Bin; Zhao, Ruiying; Li, Zhanbiao; Sun, Guojian

    2017-02-24

    BACKGROUND Cardioembolic stroke (CES), which causes 20% cause of all ischemic strokes, is associated with high mortality. Previous studies suggest that pathways play a critical role in the identification and pathogenesis of diseases. We aimed to develop an integrated approach that is able to construct individual networks of pathway cross-talk to quantify differences between patients with CES and controls. MATERIAL AND METHODS One biological data set E-GEOD-58294 was used, including 23 normal controls and 59 CES samples. We used individualized pathway aberrance score (iPAS) to assess pathway statistics of 589 Ingenuity Pathways Analysis (IPA) pathways. Random Forest (RF) classification was implemented to calculate the AUC of every network. These procedures were tested by Monte Carlo Cross-Validation for 50 bootstraps. RESULTS A total of 28 networks with AUC >0.9 were found between CES and controls. Among them, 3 networks with AUC=1.0 had the best performance for classification in 50 bootstraps. The 3 pathway networks were able to significantly identify CES versus controls, which showed as biomarkers in the regulation and development of CES. CONCLUSIONS This novel approach could identify 3 networks able to accurately classify CES and normal samples in individuals. This integrated application needs to be validated in other diseases.

  5. Personalized Analysis by Validation of Monte Carlo for Application of Pathways in Cardioembolic Stroke

    PubMed Central

    Xing, Zhangmin; Luan, Bin; Zhao, Ruiying; Li, Zhanbiao; Sun, Guojian

    2017-01-01

    Background Cardioembolic stroke (CES), which causes 20% cause of all ischemic strokes, is associated with high mortality. Previous studies suggest that pathways play a critical role in the identification and pathogenesis of diseases. We aimed to develop an integrated approach that is able to construct individual networks of pathway cross-talk to quantify differences between patients with CES and controls. Material/Methods One biological data set E-GEOD-58294 was used, including 23 normal controls and 59 CES samples. We used individualized pathway aberrance score (iPAS) to assess pathway statistics of 589 Ingenuity Pathways Analysis (IPA) pathways. Random Forest (RF) classification was implemented to calculate the AUC of every network. These procedures were tested by Monte Carlo Cross-Validation for 50 bootstraps. Results A total of 28 networks with AUC >0.9 were found between CES and controls. Among them, 3 networks with AUC=1.0 had the best performance for classification in 50 bootstraps. The 3 pathway networks were able to significantly identify CES versus controls, which showed as biomarkers in the regulation and development of CES. Conclusions This novel approach could identify 3 networks able to accurately classify CES and normal samples in individuals. This integrated application needs to be validated in other diseases. PMID:28232661

  6. Metabolic Control Analysis: A Tool for Designing Strategies to Manipulate Metabolic Pathways

    PubMed Central

    Moreno-Sánchez, Rafael; Saavedra, Emma; Rodríguez-Enríquez, Sara; Olín-Sandoval, Viridiana

    2008-01-01

    The traditional experimental approaches used for changing the flux or the concentration of a particular metabolite of a metabolic pathway have been mostly based on the inhibition or over-expression of the presumed rate-limiting step. However, the attempts to manipulate a metabolic pathway by following such approach have proved to be unsuccessful. Metabolic Control Analysis (MCA) establishes how to determine, quantitatively, the degree of control that a given enzyme exerts on flux and on the concentration of metabolites, thus substituting the intuitive, qualitative concept of rate limiting step. Moreover, MCA helps to understand (i) the underlying mechanisms by which a given enzyme exerts high or low control and (ii) why the control of the pathway is shared by several pathway enzymes and transporters. By applying MCA it is possible to identify the steps that should be modified to achieve a successful alteration of flux or metabolite concentration in pathways of biotechnological (e.g., large scale metabolite production) or clinical relevance (e.g., drug therapy). The different MCA experimental approaches developed for the determination of the flux-control distribution in several pathways are described. Full understanding of the pathway properties when is working under a variety of conditions can help to attain a successful manipulation of flux and metabolite concentration. PMID:18629230

  7. Post-transcriptional knowledge in pathway analysis increases the accuracy of phenotypes classification

    PubMed Central

    Alaimo, Salvatore; Giugno, Rosalba; Acunzo, Mario; Veneziano, Dario; Ferro, Alfredo; Pulvirenti, Alfredo

    2016-01-01

    Motivation Prediction of phenotypes from high-dimensional data is a crucial task in precision biology and medicine. Many technologies employ genomic biomarkers to characterize phenotypes. However, such elements are not sufficient to explain the underlying biology. To improve this, pathway analysis techniques have been proposed. Nevertheless, such methods have shown lack of accuracy in phenotypes classification. Results Here we propose a novel methodology called MITHrIL (Mirna enrIched paTHway Impact anaLysis) for the analysis of signaling pathways, which extends the work of Tarca et al., 2009. MITHrIL augments pathways with missing regulatory elements, such as microRNAs, and their interactions with genes. The method takes as input the expression values of genes and/or microRNAs and returns a list of pathways sorted according to their degree of deregulation, together with the corresponding statistical significance (p-values). Our analysis shows that MITHrIL outperforms its competitors even in the worst case. In addition, our method is able to correctly classify sets of tumor samples drawn from TCGA. Availability MITHrIL is freely available at the following URL: http://alpha.dmi.unict.it/mithril/ PMID:27275538

  8. Drug target identification in sphingolipid metabolism by computational systems biology tools: metabolic control analysis and metabolic pathway analysis.

    PubMed

    Ozbayraktar, F Betül Kavun; Ulgen, Kutlu O

    2010-08-01

    Sphingolipids regulate cellular processes that are critically important in cell's fate and function in cancer development and progression. This fact underlies the basics of the novel cancer therapy approach. The pharmacological manipulation of the sphingolipid metabolism in cancer therapeutics necessitates the detailed understanding of the pathway. Two computational systems biology tools are used to identify potential drug target enzymes among sphingolipid pathway that can be further utilized in drug design studies for cancer therapy. The enzymes in sphingolipid pathway were ranked according to their roles in controlling the metabolic network by metabolic control analysis. The physiologically connected reactions, i.e. biologically significant and functional modules of network, were identified by metabolic pathway analysis. The final set of candidate drug target enzymes are selected such that their manipulation leads to ceramide accumulation and long chain base phosphates depletion. The mathematical tools' efficiency for drug target identification performed in this study is validated by clinically available drugs.

  9. Endocrine-disrupting Chemicals: Review of Toxicological Mechanisms Using Molecular Pathway Analysis

    PubMed Central

    Yang, Oneyeol; Kim, Hye Lim; Weon, Jong-Il; Seo, Young Rok

    2015-01-01

    Endocrine disruptors are known to cause harmful effects to human through various exposure routes. These chemicals mainly appear to interfere with the endocrine or hormone systems. As importantly, numerous studies have demonstrated that the accumulation of endocrine disruptors can induce fatal disorders including obesity and cancer. Using diverse biological tools, the potential molecular mechanisms related with these diseases by exposure of endocrine disruptors. Recently, pathway analysis, a bioinformatics tool, is being widely used to predict the potential mechanism or biological network of certain chemicals. In this review, we initially summarize the major molecular mechanisms involved in the induction of the above mentioned diseases by endocrine disruptors. Additionally, we provide the potential markers and signaling mechanisms discovered via pathway analysis under exposure to representative endocrine disruptors, bisphenol, diethylhexylphthalate, and nonylphenol. The review emphasizes the importance of pathway analysis using bioinformatics to finding the specific mechanisms of toxic chemicals, including endocrine disruptors. PMID:25853100

  10. Decision Analysis Tool to Compare Energy Pathways for Transportation

    SciTech Connect

    Bloyd, Cary N.; Stork, Kevin

    2011-02-01

    With the goals of reducing greenhouse gas emissions, oil imports, and energy costs, a wide variety of automotive technologies are proposed to replace the traditional gasoline-powered internal combustion engine (g-ICE). A prototype model, Analytica Transportation Energy Analysis Model (ATEAM), has been developed using the Analytica decision modeling environment, visualizing the structure as a hierarchy of influence diagrams. The report summarized the FY2010 ATEAM accomplishments.

  11. Genome wide expression analysis in HPV16 Cervical Cancer: identification of altered metabolic pathways

    PubMed Central

    Pérez-Plasencia, Carlos; Vázquez-Ortiz, Guelaguetza; López-Romero, Ricardo; Piña-Sanchez, Patricia; Moreno, José; Salcedo, Mauricio

    2007-01-01

    Background Cervical carcinoma (CC) is a leading cause of death among women worldwide. Human papilloma virus (HPV) is a major etiological factor in CC and HPV 16 is the more frequent viral type present. Our aim was to characterize metabolic pathways altered in HPV 16 tumor samples by means of transcriptome wide analysis and bioinformatics tools for visualizing expression data in the context of KEGG biological pathways. Results We found 2,067 genes significantly up or down-modulated (at least 2-fold) in tumor clinical samples compared to normal tissues, representing ~3.7% of analyzed genes. Cervical carcinoma was associated with an important up-regulation of Wnt signaling pathway, which was validated by in situ hybridization in clinical samples. Other up-regulated pathways were those of calcium signaling and MAPK signaling, as well as cell cycle-related genes. There was down-regulation of focal adhesion, TGF-β signaling, among other metabolic pathways. Conclusion This analysis of HPV 16 tumors transcriptome could be useful for the identification of genes and molecular pathways involved in the pathogenesis of cervical carcinoma. Understanding the possible role of these proteins in the pathogenesis of CC deserves further studies. PMID:17822553

  12. Pathways enrichment analysis for differentially expressed genes in squamous lung cancer.

    PubMed

    Qian, Liqiang; Luo, Qingquan; Zhao, Xiaojing; Huang, Jia

    2014-01-01

    Squamous lung cancer (SQLC) is a common type of lung cancer, but its oncogenesis mechanism is not so clear. The aim of this study was to screen the potential pathways changed in SQLC and elucidate the mechanism of it. Published microarray data of GSE3268 series was downloaded from Gene Expression Omnibus (GEO). Significance analysis of microarrays was performed using software R, and differentially expressed genes (DEGs) were harvested. The functions and pathways of DEGs were mapped in Gene Otology and KEGG pathway database, respectively. A total of 2961 genes were filtered as DEGs between normal and SQLC cells. Cell cycle and metabolism were the mainly changed functions of SQLC cells. Meanwhile genes such as MCM, RFC, FEN1, and POLD may induce SQLC through DNA replication pathway, and genes such as PTTG1, CCNB1, CDC6, and PCNA may be involved in SQLC through cell cycle pathway. It is demonstrated that pathway analysis is useful in the identification of target genes in SQLC.

  13. Analysis of Important Gene Ontology Terms and Biological Pathways Related to Pancreatic Cancer.

    PubMed

    Yin, Hang; Wang, ShaoPeng; Zhang, Yu-Hang; Cai, Yu-Dong; Liu, Hailin

    2016-01-01

    Pancreatic cancer is a serious disease that results in more than thirty thousand deaths around the world per year. To design effective treatments, many investigators have devoted themselves to the study of biological processes and mechanisms underlying this disease. However, it is far from complete. In this study, we tried to extract important gene ontology (GO) terms and KEGG pathways for pancreatic cancer by adopting some existing computational methods. Genes that have been validated to be related to pancreatic cancer and have not been validated were represented by features derived from GO terms and KEGG pathways using the enrichment theory. A popular feature selection method, minimum redundancy maximum relevance, was employed to analyze these features and extract important GO terms and KEGG pathways. An extensive analysis of the obtained GO terms and KEGG pathways was provided to confirm the correlations between them and pancreatic cancer.

  14. Analysis of Important Gene Ontology Terms and Biological Pathways Related to Pancreatic Cancer

    PubMed Central

    Yin, Hang; Wang, ShaoPeng; Zhang, Yu-Hang

    2016-01-01

    Pancreatic cancer is a serious disease that results in more than thirty thousand deaths around the world per year. To design effective treatments, many investigators have devoted themselves to the study of biological processes and mechanisms underlying this disease. However, it is far from complete. In this study, we tried to extract important gene ontology (GO) terms and KEGG pathways for pancreatic cancer by adopting some existing computational methods. Genes that have been validated to be related to pancreatic cancer and have not been validated were represented by features derived from GO terms and KEGG pathways using the enrichment theory. A popular feature selection method, minimum redundancy maximum relevance, was employed to analyze these features and extract important GO terms and KEGG pathways. An extensive analysis of the obtained GO terms and KEGG pathways was provided to confirm the correlations between them and pancreatic cancer. PMID:27957501

  15. APPLICATION OF BAYESIAN MONTE CARLO ANALYSIS TO A LAGRANGIAN PHOTOCHEMICAL AIR QUALITY MODEL. (R824792)

    EPA Science Inventory

    Uncertainties in ozone concentrations predicted with a Lagrangian photochemical air quality model have been estimated using Bayesian Monte Carlo (BMC) analysis. Bayesian Monte Carlo analysis provides a means of combining subjective "prior" uncertainty estimates developed ...

  16. Integrated In Silico Analysis of Pathway Designs for Synthetic Photo-Electro-Autotrophy.

    PubMed

    Volpers, Michael; Claassens, Nico J; Noor, Elad; van der Oost, John; de Vos, Willem M; Kengen, Servé W M; Martins Dos Santos, Vitor A P

    2016-01-01

    The strong advances in synthetic biology enable the engineering of novel functions and complex biological features in unprecedented ways, such as implementing synthetic autotrophic metabolism into heterotrophic hosts. A key challenge for the sustainable production of fuels and chemicals entails the engineering of synthetic autotrophic organisms that can effectively and efficiently fix carbon dioxide by using sustainable energy sources. This challenge involves the integration of carbon fixation and energy uptake systems. A variety of carbon fixation pathways and several types of photosystems and other energy uptake systems can be chosen and, potentially, modularly combined to design synthetic autotrophic metabolism. Prior to implementation, these designs can be evaluated by the combination of several computational pathway analysis techniques. Here we present a systematic, integrated in silico analysis of photo-electro-autotrophic pathway designs, consisting of natural and synthetic carbon fixation pathways, a proton-pumping rhodopsin photosystem for ATP regeneration and an electron uptake pathway. We integrated Flux Balance Analysis of the heterotrophic chassis Escherichia coli with kinetic pathway analysis and thermodynamic pathway analysis (Max-min Driving Force). The photo-electro-autotrophic designs are predicted to have a limited potential for anaerobic, autotrophic growth of E. coli, given the relatively low ATP regenerating capacity of the proton pumping rhodopsin photosystems and the high ATP maintenance of E. coli. If these factors can be tackled, our analysis indicates the highest growth potential for the natural reductive tricarboxylic acid cycle and the synthetic pyruvate synthase-pyruvate carboxylate -glyoxylate bicycle. Both carbon fixation cycles are very ATP efficient, while maintaining fast kinetics, which also results in relatively low estimated protein costs for these pathways. Furthermore, the synthetic bicycles are highly thermodynamic favorable

  17. Integrated In Silico Analysis of Pathway Designs for Synthetic Photo-Electro-Autotrophy

    PubMed Central

    Noor, Elad; van der Oost, John; de Vos, Willem M.; Kengen, Servé W. M.; Martins dos Santos, Vitor A. P.

    2016-01-01

    The strong advances in synthetic biology enable the engineering of novel functions and complex biological features in unprecedented ways, such as implementing synthetic autotrophic metabolism into heterotrophic hosts. A key challenge for the sustainable production of fuels and chemicals entails the engineering of synthetic autotrophic organisms that can effectively and efficiently fix carbon dioxide by using sustainable energy sources. This challenge involves the integration of carbon fixation and energy uptake systems. A variety of carbon fixation pathways and several types of photosystems and other energy uptake systems can be chosen and, potentially, modularly combined to design synthetic autotrophic metabolism. Prior to implementation, these designs can be evaluated by the combination of several computational pathway analysis techniques. Here we present a systematic, integrated in silico analysis of photo-electro-autotrophic pathway designs, consisting of natural and synthetic carbon fixation pathways, a proton-pumping rhodopsin photosystem for ATP regeneration and an electron uptake pathway. We integrated Flux Balance Analysis of the heterotrophic chassis Escherichia coli with kinetic pathway analysis and thermodynamic pathway analysis (Max-min Driving Force). The photo-electro-autotrophic designs are predicted to have a limited potential for anaerobic, autotrophic growth of E. coli, given the relatively low ATP regenerating capacity of the proton pumping rhodopsin photosystems and the high ATP maintenance of E. coli. If these factors can be tackled, our analysis indicates the highest growth potential for the natural reductive tricarboxylic acid cycle and the synthetic pyruvate synthase–pyruvate carboxylate -glyoxylate bicycle. Both carbon fixation cycles are very ATP efficient, while maintaining fast kinetics, which also results in relatively low estimated protein costs for these pathways. Furthermore, the synthetic bicycles are highly thermodynamic

  18. A Powerful Procedure for Pathway-Based Meta-analysis Using Summary Statistics Identifies 43 Pathways Associated with Type II Diabetes in European Populations

    PubMed Central

    Zhang, Han; Wheeler, William; Hyland, Paula L.; Yang, Yifan; Shi, Jianxin; Chatterjee, Nilanjan; Yu, Kai

    2016-01-01

    Meta-analysis of multiple genome-wide association studies (GWAS) has become an effective approach for detecting single nucleotide polymorphism (SNP) associations with complex traits. However, it is difficult to integrate the readily accessible SNP-level summary statistics from a meta-analysis into more powerful multi-marker testing procedures, which generally require individual-level genetic data. We developed a general procedure called Summary based Adaptive Rank Truncated Product (sARTP) for conducting gene and pathway meta-analysis that uses only SNP-level summary statistics in combination with genotype correlation estimated from a panel of individual-level genetic data. We demonstrated the validity and power advantage of sARTP through empirical and simulated data. We conducted a comprehensive pathway-based meta-analysis with sARTP on type 2 diabetes (T2D) by integrating SNP-level summary statistics from two large studies consisting of 19,809 T2D cases and 111,181 controls with European ancestry. Among 4,713 candidate pathways from which genes in neighborhoods of 170 GWAS established T2D loci were excluded, we detected 43 T2D globally significant pathways (with Bonferroni corrected p-values < 0.05), which included the insulin signaling pathway and T2D pathway defined by KEGG, as well as the pathways defined according to specific gene expression patterns on pancreatic adenocarcinoma, hepatocellular carcinoma, and bladder carcinoma. Using summary data from 8 eastern Asian T2D GWAS with 6,952 cases and 11,865 controls, we showed 7 out of the 43 pathways identified in European populations remained to be significant in eastern Asians at the false discovery rate of 0.1. We created an R package and a web-based tool for sARTP with the capability to analyze pathways with thousands of genes and tens of thousands of SNPs. PMID:27362418

  19. An angiosperm-wide analysis of the gynodioecy–dioecy pathway

    PubMed Central

    Dufay, M.; Champelovier, P.; Käfer, J.; Henry, J. P.; Mousset, S.; Marais, G. A. B.

    2014-01-01

    Background and Aims About 6 % of an estimated total of 240 000 species of angiosperms are dioecious. The main precursors of this sexual system are thought to be monoecy and gynodioecy. A previous angiosperm-wide study revealed that many dioecious species have evolved through the monoecy pathway; some case studies and a large body of theoretical research also provide evidence in support of the gynodioecy pathway. If plants have evolved through the gynodioecy pathway, gynodioecious and dioecious species should co-occur in the same genera. However, to date, no large-scale analysis has been conducted to determine the prevalence of the gynodioecy pathway in angiosperms. In this study, this gap in knowledge was addressed by performing an angiosperm-wide survey in order to test for co-occurrence as evidence of the gynodioecy pathway. Methods Data from different sources were compiled to obtain (to our knowledge) the largest dataset on gynodioecy available, with 275 genera that include at least one gynodioecious species. This dataset was combined with a dioecy dataset from the literature, and a study was made of how often dioecious and gynodioecious species could be found in the same genera using a contingency table framework. Key Results It was found that, overall, angiosperm genera with both gynodioecious and dioecious species occur more frequently than expected, in agreement with the gynodioecy pathway. Importantly, this trend holds when studying different classes separately (or sub-classes, orders and families), suggesting that the gynodioecy pathway is not restricted to a few taxa but may instead be widespread in angiosperms. Conclusions This work complements that previously carried out on the monoecy pathway and suggests that gynodioecy is also a common pathway in angiosperms. The results also identify angiosperm families where some (or all) dioecious species may have evolved from gynodioecious precursors. These families could be the targets of future small

  20. Summary of the BIOMOVS A4 scenario: Testing models of the air-pasture-cow milk pathway using Chernobyl fallout data

    SciTech Connect

    Peterson, S.R.; Hoffman, F.O.; Koehler, H.

    1996-08-01

    A unique opportunity to test dose assessment models arose after the Chernobyl reactor accident. During the passage of the contaminated plume, concentrations of {sup 131}I and {sup 137}Cs in air, pasture, and cow`s milk were collected at various sites in the northern hemisphere. Afterwards, contaminated pasture and milk samples were analyzed over time. Under the auspices of the Biospheric Model Validation Study (BIOMOVS), data from 13 sites for {sup 131}I and 10 sites for {sup 137}Cs were used to test model predictions for the air-pasture-cow milk pathway. Calculations were submitted for 23 models, 10 of which were quasi-steady state. The others were time-dependent. Daily predictions and predictions of time-integrated concentration of {sup 131}I and {sup 137}Cs in pasture grass and milk for six months post-accident were calculated and compared with observed data. Testing against data from several locations over time for several steps in the air-to-milk pathway resulted in a better understanding of important processes and how they should be modeled. This model testing exercise showed both the strengths and weaknesses of the models and revealed the importance of testing all parts of dose assessment models whenever possible. 19 refs., 14 figs., 4 tabs.

  1. Analysis of U.S. residential air leakage database

    SciTech Connect

    Chan, Wanyu R.; Price, Phillip N.; Sohn, Michael D.; Gadgil, Ashok J.

    2003-07-01

    The air leakage of a building envelope can be determined from fan pressurization measurements with a blower door. More than 70,000 air leakage measurements have been compiled into a database. In addition to air leakage, the database includes other important characteristics of the dwellings tested, such as floor area, year built, and location. There are also data for some houses on the presence of heating ducts, and floor/basement construction type. The purpose of this work is to identify house characteristics that can be used to predict air leakage. We found that the distribution of leakage normalized with floor area of the house is roughly lognormal. Year built and floor area are the two most significant factors to consider when predicting air leakage: older and smaller houses tend to have higher normalized leakage areas compared to newer and larger ones. Results from multiple linear regression of normalized leakage with respect to these two factors are presented for three types of houses: low-income, energy-efficient, and conventional. We demonstrate a method of using the regression model in conjunction with housing characteristics published by the US Census Bureau to derive a distribution that describes the air leakage of the single-family detached housing stock. Comparison of our estimates with published datasets of air exchange rates suggests that the regression model generates accurate estimates of air leakage distribution.

  2. Future Technologies Needs Analysis. An Air University Staff Report.

    ERIC Educational Resources Information Center

    Reed, Dorothy D.

    This report summarizes the findings of a survey of all permanently assigned personnel at the Air University at Maxwell Air Force Base (Alabama) to determine what future workplace technologies will be needed to support the university's two major programs, Professional Military Education (PME) and Professional Continuing Education (PCE). The…

  3. Air Pollution Monitoring Site Selection by Multiple Criteria Decision Analysis

    EPA Science Inventory

    Criteria air pollutants (particulate matter, sulfur dioxide, oxides of nitrogen, volatile organic compounds, and carbon monoxide) as well as toxic air pollutants are a global concern. A particular scenario that is receiving increased attention in the research is the exposure to t...

  4. Genomic analysis and selected molecular pathways in rare cancers

    NASA Astrophysics Data System (ADS)

    Liu, Stephen V.; Lenkiewicz, Elizabeth; Evers, Lisa; Holley, Tara; Kiefer, Jeffrey; Ruiz, Christian; Glatz, Katharina; Bubendorf, Lukas; Demeure, Michael J.; Eng, Cathy; Ramanathan, Ramesh K.; Von Hoff, Daniel D.; Barrett, Michael T.

    2012-12-01

    It is widely accepted that many cancers arise as a result of an acquired genomic instability and the subsequent evolution of tumor cells with variable patterns of selected and background aberrations. The presence and behaviors of distinct neoplastic cell populations within a patient's tumor may underlie multiple clinical phenotypes in cancers. A goal of many current cancer genome studies is the identification of recurring selected driver events that can be advanced for the development of personalized therapies. Unfortunately, in the majority of rare tumors, this type of analysis can be particularly challenging. Large series of specimens for analysis are simply not available, allowing recurring patterns to remain hidden. In this paper, we highlight the use of DNA content-based flow sorting to identify and isolate DNA-diploid and DNA-aneuploid populations from tumor biopsies as a strategy to comprehensively study the genomic composition and behaviors of individual cancers in a series of rare solid tumors: intrahepatic cholangiocarcinoma, anal carcinoma, adrenal leiomyosarcoma, and pancreatic neuroendocrine tumors. We propose that the identification of highly selected genomic events in distinct tumor populations within each tumor can identify candidate driver events that can facilitate the development of novel, personalized treatment strategies for patients with cancer.

  5. Atmospheric Ionizing Radiation (AIR) ER-2 Preflight Analysis

    NASA Technical Reports Server (NTRS)

    Tai, Hsiang; Wilson, John W.; Maiden, D. L.

    1998-01-01

    Atmospheric ionizing radiation (AIR) produces chemically active radicals in biological tissues that alter the cell function or result in cell death. The AIR ER-2 flight measurements will enable scientists to study the radiation risk associated with the high-altitude operation of a commercial supersonic transport. The ER-2 radiation measurement flights will follow predetermined, carefully chosen courses to provide an appropriate database matrix which will enable the evaluation of predictive modeling techniques. Explicit scientific results such as dose rate, dose equivalent rate, magnetic cutoff, neutron flux, and air ionization rate associated with those flights are predicted by using the AIR model. Through these flight experiments, we will further increase our knowledge and understanding of the AIR environment and our ability to assess the risk from the associated hazard.

  6. Isentropic analysis of polar cold air mass streams

    NASA Astrophysics Data System (ADS)

    Iwasaki, Toshiki; Kanno, Yuki

    2015-04-01

    1. Introduction A diagnostic method is presented of polar cold air mass streams defined below a threshold potential temperature. The isentropic threshold facilitates a Lagrangian view of the cold air mass streams from diabatic generation to disappearance. 2. Mass-weighted isentropic zonal mean (MIM) cold air streams In winter hemispheres, MIM's mass stream functions show a distinct extratropical direct (ETD) cell in addition to the Hadley cell. The mass stream functions have local maxima at around (280K, 45N) for NH winter and, around (280K, 50S) for SH winter. Thus, =280K may be appropriate to a threshold of the polar cold air mass for both hemispheres. The high-latitude downward motion indicates the diabatic generation of cold air mass, whereas the mid-latitude equatorward flow does its outbreak. The strength of equatorward flow is under significant control of wave-mean flow interactions. 3. Geographical distribution of the cold air mass streams in the NH winter In the NH winter, the polar cold air mass flux has two distinct mainstreams, hereafter called as East Asian (EA) stream and the North American (NA) stream. The former grows over the northern part of the Eurasian continent, turns down southeastward toward East Asia and disappears over the western North Pacific Ocean. The latter grows over the Arctic Ocean, flows toward the East Coast of North America and disappears over the western North Atlantic Ocean. These coincide well with main routes of cold surges. 4. Comparison between NH and SH winter streams The cold air mass streams in NH winter are more asymmetric than those in SH winter. The NH total cold air mass below =280K is about 1.5 times greater than the SH one. These come mainly from the topography and land-sea distribution. The mid-latitude mountains steer the cold air mass streams on the northern sides and enhance the residence time over its genesis region.

  7. Characterization of genes and pathways that respond to heat stress in Holstein calves through transcriptome analysis.

    PubMed

    Srikanth, Krishnamoorthy; Kwon, Anam; Lee, Eunjin; Chung, Hoyoung

    2017-01-01

    This study aimed to investigate the genes and pathways that respond to heat stress in Holstein bull calves exposed to severe ranges of temperature and humidity. A total of ten animals from 4 to 6 months of age were subjected to heat stress at 37 °C and 90 % humidity for 12 h. Skin and rectal temperatures were measured before and after heat stress; while no correlation was found between them before heat stress, a moderate correlation was detected after heat stress, confirming rectal temperature to be a better barometer for monitoring heat stress. RNAseq analysis identified 8567 genes to be differentially regulated, out of which 465 genes were significantly upregulated (≥2-fold, P < 0.05) and 49 genes were significantly downregulated (≤2-fold, P < 0.05) in response to heat stress. Significant terms and pathways enriched in response to heat stress included chaperones, cochaperones, cellular response to heat stress, phosphorylation, kinase activation, immune response, apoptosis, Toll-like receptor signaling pathway, Pi3K/AKT activation, protein processing in endoplasmic reticulum, interferon signaling, pathways in cancer, estrogen signaling pathway, and MAPK signaling pathway. The differentially expressed genes were validated by quantitative real-time PCR analysis, which confirmed the tendency of the expression. The genes and pathways identified in this analysis extend our understanding of transcriptional response to heat stress and their likely functioning in adapting the animal to hyperthermic stress. The identified genes could be used as candidate genes for association studies to select and breed animals with improved heat tolerance.

  8. Comparative analysis of HOG pathway proteins to generate hypotheses for functional analysis.

    PubMed

    Krantz, Marcus; Becit, Evren; Hohmann, Stefan

    2006-03-01

    Comparative genomics allows comparison of different proteins that execute presumably identical functions in different organisms. In contrast to paralogues, orthologues per definition perform the same function and interact with the same partners and, consequently, should display conservation in all these properties. We have employed 20 fungal genomes to analyse key components of the high osmolarity glycerol signalling pathway of Saccharomyces cerevisiae. Among the proteins scrutinised are a complete phosphotransfer module, a MAP kinase, two scaffold proteins, one of which is also a MAPKK, and two transcription factors. Sequence alignments, domain structure and size analysis, combined with the rich information available in the literature, allowed us to probe previous structural and functional studies and to generate hypotheses for future experimental studies. Although certain domains are too highly conserved across fungal species for meaningful comparative studies, others, like interaction domains, can be studied in closely related species. Moreover, putative functionally relevant sites for protein modifications can be identified in such comparative studies. We provide several relevant examples and present a number of previously un(der)characterised domains of potential functional significance in osmosensing and signal transduction. We propose that any functional protein analysis in fungi should make use of the unique resource that fungal genome sequences offer.

  9. Network Analysis Identifies Disease-Specific Pathways for Parkinson's Disease.

    PubMed

    Monti, Chiara; Colugnat, Ilaria; Lopiano, Leonardo; Chiò, Adriano; Alberio, Tiziana

    2016-12-21

    Neurodegenerative diseases are characterized by the progressive loss of specific neurons in selected regions of the central nervous system. The main clinical manifestation (movement disorders, cognitive impairment, and/or psychiatric disturbances) depends on the neuron population being primarily affected. Parkinson's disease is a common movement disorder, whose etiology remains mostly unknown. Progressive loss of dopaminergic neurons in the substantia nigra causes an impairment of the motor control. Some of the pathogenetic mechanisms causing the progressive deterioration of these neurons are not specific for Parkinson's disease but are shared by other neurodegenerative diseases, like Alzheimer's disease and amyotrophic lateral sclerosis. Here, we performed a meta-analysis of the literature of all the quantitative proteomic investigations of neuronal alterations in different models of Parkinson's disease, Alzheimer's disease, and amyotrophic lateral sclerosis to distinguish between general and Parkinson's disease-specific pattern of neurodegeneration. Then, we merged proteomics data with genetics information from the DisGeNET database. The comparison of gene and protein information allowed us to identify 25 proteins involved uniquely in Parkinson's disease and we verified the alteration of one of them, i.e., transaldolase 1 (TALDO1), in the substantia nigra of 5 patients. By using open-source bioinformatics tools, we identified the biological processes specifically affected in Parkinson's disease, i.e., proteolysis, mitochondrion organization, and mitophagy. Eventually, we highlighted four cellular component complexes mostly involved in the pathogenesis: the proteasome complex, the protein phosphatase 2A, the chaperonins CCT complex, and the complex III of the respiratory chain.

  10. Analysis and Engineering of Metabolic Pathway Fluxes in Corynebacterium glutamicum

    NASA Astrophysics Data System (ADS)

    Wittmann, Christoph

    The Gram-positive soil bacterium Corynebacterium glutamicum was discovered as a natural overproducer of glutamate about 50 years ago. Linked to the steadily increasing economical importance of this microorganism for production of glutamate and other amino acids, the quest for efficient production strains has been an intense area of research during the past few decades. Efficient production strains were created by applying classical mutagenesis and selection and especially metabolic engineering strategies with the advent of recombinant DNA technology. Hereby experimental and computational approaches have provided fascinating insights into the metabolism of this microorganism and directed strain engineering. Today, C. glutamicum is applied to the industrial production of more than 2 million tons of amino acids per year. The huge achievements in recent years, including the sequencing of the complete genome and efficient post genomic approaches, now provide the basis for a new, fascinating era of research - analysis of metabolic and regulatory properties of C. glutamicum on a global scale towards novel and superior bioprocesses.

  11. Spatial assessment of air quality patterns in Malaysia using multivariate analysis

    NASA Astrophysics Data System (ADS)

    Dominick, Doreena; Juahir, Hafizan; Latif, Mohd Talib; Zain, Sharifuddin M.; Aris, Ahmad Zaharin

    2012-12-01

    This study aims to investigate possible sources of air pollutants and the spatial patterns within the eight selected Malaysian air monitoring stations based on a two-year database (2008-2009). The multivariate analysis was applied on the dataset. It incorporated Hierarchical Agglomerative Cluster Analysis (HACA) to access the spatial patterns, Principal Component Analysis (PCA) to determine the major sources of the air pollution and Multiple Linear Regression (MLR) to assess the percentage contribution of each air pollutant. The HACA results grouped the eight monitoring stations into three different clusters, based on the characteristics of the air pollutants and meteorological parameters. The PCA analysis showed that the major sources of air pollution were emissions from motor vehicles, aircraft, industries and areas of high population density. The MLR analysis demonstrated that the main pollutant contributing to variability in the Air Pollutant Index (API) at all stations was particulate matter with a diameter of less than 10 μm (PM10). Further MLR analysis showed that the main air pollutant influencing the high concentration of PM10 was carbon monoxide (CO). This was due to combustion processes, particularly originating from motor vehicles. Meteorological factors such as ambient temperature, wind speed and humidity were also noted to influence the concentration of PM10.

  12. Aircraft/Air Traffic Management Functional Analysis Model. Version 2.0; User's Guide

    NASA Technical Reports Server (NTRS)

    Etheridge, Melvin; Plugge, Joana; Retina, Nusrat

    1998-01-01

    The Aircraft/Air Traffic Management Functional Analysis Model, Version 2.0 (FAM 2.0), is a discrete event simulation model designed to support analysis of alternative concepts in air traffic management and control. FAM 2.0 was developed by the Logistics Management Institute (LMI) a National Aeronautics and Space Administration (NASA) contract. This document provides a guide for using the model in analysis. Those interested in making enhancements or modification to the model should consult the companion document, Aircraft/Air Traffic Management Functional Analysis Model, Version 2.0 Technical Description.

  13. Transcriptomic analysis in the developing zebrafish embryo after compound exposure: Individual gene expression and pathway regulation

    SciTech Connect

    Hermsen, Sanne A.B.; Pronk, Tessa E.; Brandhof, Evert-Jan van den; Ven, Leo T.M. van der; Piersma, Aldert H.

    2013-10-01

    The zebrafish embryotoxicity test is a promising alternative assay for developmental toxicity. Classically, morphological assessment of the embryos is applied to evaluate the effects of compound exposure. However, by applying differential gene expression analysis the sensitivity and predictability of the test may be increased. For defining gene expression signatures of developmental toxicity, we explored the possibility of using gene expression signatures of compound exposures based on commonly expressed individual genes as well as based on regulated gene pathways. Four developmental toxic compounds were tested in concentration-response design, caffeine, carbamazepine, retinoic acid and valproic acid, and two non-embryotoxic compounds, D-mannitol and saccharin, were included. With transcriptomic analyses we were able to identify commonly expressed genes, which were mostly development related, after exposure to the embryotoxicants. We also identified gene pathways regulated by the embryotoxicants, suggestive of their modes of action. Furthermore, whereas pathways may be regulated by all compounds, individual gene expression within these pathways can differ for each compound. Overall, the present study suggests that the use of individual gene expression signatures as well as pathway regulation may be useful starting points for defining gene biomarkers for predicting embryotoxicity. - Highlights: • The zebrafish embryotoxicity test in combination with transcriptomics was used. • We explored two approaches of defining gene biomarkers for developmental toxicity. • Four compounds in concentration-response design were tested. • We identified commonly expressed individual genes as well as regulated gene pathways. • Both approaches seem suitable starting points for defining gene biomarkers.

  14. Kinetic Analysis of Competitive Electrocatalytic Pathways: New Insights into Hydrogen Production with Nickel Electrocatalysts

    SciTech Connect

    Wiedner, Eric S.; Brown, Houston J.; Helm, Monte L.

    2016-01-20

    The hydrogen production electrocatalyst Ni(PPh2NPh2)22+ (1) is capable of traversing multiple electrocatalytic pathways. When using dimethylformamidium, DMF(H)+, the mechanism of formation of H2 catalyzed by 1 changes from an ECEC to an EECC mechanism as the potential approaches the Ni(I/0) couple. Two recent electrochemical methods, current-potential analysis and foot-of-the-wave analysis (FOWA), were performed on 1 to measure the detailed chemical kinetics of the competing ECEC and EECC pathways. A sensitivity analysis was performed on the electrochemical methods using digital simulations to gain a better understanding of their strengths and limitations. Notably, chemical rate constants were significantly underestimated when not accounting for electron transfer kinetics, even when electron transfer was fast enough to afford a reversible non-catalytic wave. The EECC pathway of 1 was found to be faster than the ECEC pathway under all conditions studied. Using buffered DMF: DMF(H)+ mixtures led to an increase in the catalytic rate constant (kobs) of the EECC pathway, but kobs for the ECEC pathway did not change when using buffered acid. Further kinetic analysis of the ECEC path revealed that added base increases the rate of isomerization of the exo-protonated Ni(0) isomers to the catalytically active endo-isomers, but decreases the net rate of protonation of Ni(I). FOWA on 1 did not provide accurate rate constants due to incomplete reduction of the exo-protonated Ni(I) intermediate at the foot of the wave, but FOWA could be used to estimate the reduction potential of this previously undetected intermediate. This research was supported as part of the Center for Molecular Electrocatalysis, an Energy Frontier Research Center funded by the U.S. Department of Energy, Office of Science, Office of Basic Energy Sciences. Pacific Northwest National Laboratory is operated by Battelle for the U.S. Department of Energy.

  15. A PRINCIPAL COMPONENT ANALYSIS OF THE CLEAN AIR STATUS AND TRENDS NETWORK (CASTNET) AIR CONCENTRATION DATA

    EPA Science Inventory

    The spatial and temporal variability of ambient air concentrations of SO2, SO42-, NO3, HNO3, and NH4+ obtained from EPA's CASTNet was examined using an objective, statistically based technique...

  16. Gene-set meta-analysis of lung cancer identifies pathway related to systemic lupus erythematosus

    PubMed Central

    Sohns, Melanie; Friedrichs, Stefanie; Hung, Rayjean J.; Fehringer, Gord; McLaughlin, John; Amos, Christopher I.; Brennan, Paul; Risch, Angela; Brüske, Irene; Caporaso, Neil E.; Landi, Maria Teresa; Christiani, David C.; Wei, Yongyue; Bickeböller, Heike

    2017-01-01

    Introduction Gene-set analysis (GSA) is an approach using the results of single-marker genome-wide association studies when investigating pathways as a whole with respect to the genetic basis of a disease. Methods We performed a meta-analysis of seven GSAs for lung cancer, applying the method META-GSA. Overall, the information taken from 11,365 cases and 22,505 controls from within the TRICL/ILCCO consortia was used to investigate a total of 234 pathways from the Kyoto Encyclopedia of Genes and Genomes (KEGG) database. Results META-GSA reveals the systemic lupus erythematosus KEGG pathway hsa05322, driven by the gene region 6p21-22, as also implicated in lung cancer (p = 0.0306). This gene region is known to be associated with squamous cell lung carcinoma. The most important genes driving the significance of this pathway belong to the genomic areas HIST1-H4L, -1BN, -2BN, -H2AK, -H4K and C2/C4A/C4B. Within these areas, the markers most significantly associated with LC are rs13194781 (located within HIST12BN) and rs1270942 (located between C2 and C4A). Conclusions We have discovered a pathway currently marked as specific to systemic lupus erythematosus as being significantly implicated in lung cancer. The gene region 6p21-22 in this pathway appears to be more extensively associated with lung cancer than previously assumed. Given wide-stretched linkage disequilibrium to the area APOM/BAG6/MSH5, there is currently simply not enough information or evidence to conclude whether the potential pleiotropy of lung cancer and systemic lupus erythematosus is spurious, biological, or mediated. Further research into this pathway and gene region will be necessary. PMID:28273134

  17. Genome-wide analysis of a Wnt1-regulated transcriptional network implicates neurodegenerative pathways.

    PubMed

    Wexler, Eric M; Rosen, Ezra; Lu, Daning; Osborn, Gregory E; Martin, Elizabeth; Raybould, Helen; Geschwind, Daniel H

    2011-10-04

    Wnt proteins are critical to mammalian brain development and function. The canonical Wnt signaling pathway involves the stabilization and nuclear translocation of β-catenin; however, Wnt also signals through alternative, noncanonical pathways. To gain a systems-level, genome-wide view of Wnt signaling, we analyzed Wnt1-stimulated changes in gene expression by transcriptional microarray analysis in cultured human neural progenitor (hNP) cells at multiple time points over a 72-hour time course. We observed a widespread oscillatory-like pattern of changes in gene expression, involving components of both the canonical and the noncanonical Wnt signaling pathways. A higher-order, systems-level analysis that combined independent component analysis, waveform analysis, and mutual information-based network construction revealed effects on pathways related to cell death and neurodegenerative disease. Wnt effectors were tightly clustered with presenilin1 (PSEN1) and granulin (GRN), which cause dominantly inherited forms of Alzheimer's disease and frontotemporal dementia (FTD), respectively. We further explored a potential link between Wnt1 and GRN and found that Wnt1 decreased GRN expression by hNPs. Conversely, GRN knockdown increased WNT1 expression, demonstrating that Wnt and GRN reciprocally regulate each other. Finally, we provided in vivo validation of the in vitro findings by analyzing gene expression data from individuals with FTD. These unbiased and genome-wide analyses provide evidence for a connection between Wnt signaling and the transcriptional regulation of neurodegenerative disease genes.

  18. [Current service invention patents and growth pathways on basis of cluster analysis].

    PubMed

    Yang, Xu-jie; Xiao, Shi-ying

    2012-09-01

    This study aims for enhancing quantity and quality of patents of traditional Chinese medicine compounds of traditional Chinese medicine enterprises, traditional Chinese medicine colleges and relevant institutions while building an efficient pathway for patent protection using simple statistics and cluster analysis, with service invention patent holders of traditional Chinese medicine compounds as the study object.

  19. Proteomic analysis reveals diverse proline hydroxylation-mediated oxygen-sensing cellular pathways in cancer cells

    PubMed Central

    Liu, Bing; Gao, Yankun; Ruan, Hai-Bin; Chen, Yue

    2016-01-01

    Proline hydroxylation is a critical cellular mechanism regulating oxygen-response pathways in tumor initiation and progression. Yet, its substrate diversity and functions remain largely unknown. Here, we report a system-wide analysis to characterize proline hydroxylation substrates in cancer cells using an immunoaffinity-purification assisted proteomics strategy. We identified 562 sites from 272 proteins in HeLa cells. Bioinformatic analysis revealed that proline hydroxylation substrates are significantly enriched with mRNA processing and stress-response cellular pathways with canonical and diverse flanking sequence motifs. Structural analysis indicates a significant enrichment of proline hydroxylation participating in the secondary structure of substrate proteins. Our study identified and validated Brd4, a key transcription factor, as a novel proline hydroxylation substrate. Functional analysis showed that the inhibition of proline hydroxylation pathway significantly reduced the proline hydroxylation abundance on Brd4 and affected Brd4-mediated transcriptional activity as well as cell proliferation in AML leukemia cells. Taken together, our study identified a broad regulatory role of proline hydroxylation in cellular oxygen-sensing pathways and revealed potentially new targets that dynamically respond to hypoxia microenvironment in tumor cells. PMID:27764789

  20. Transcriptome and Metabolite analysis reveal candidate genes of the cardiac glycoside biosynthetic pathway from Calotropis procera

    PubMed Central

    Pandey, Akansha; Swarnkar, Vishakha; Pandey, Tushar; Srivastava, Piush; Kanojiya, Sanjeev; Mishra, Dipak Kumar; Tripathi, Vineeta

    2016-01-01

    Calotropis procera is a medicinal plant of immense importance due to its pharmaceutical active components, especially cardiac glycosides (CG). As genomic resources for this plant are limited, the genes involved in CG biosynthetic pathway remain largely unknown till date. Our study on stage and tissue specific metabolite accumulation showed that CG’s were maximally accumulated in stems of 3 month old seedlings. De novo transcriptome sequencing of same was done using high throughput Illumina HiSeq platform generating 44074 unigenes with average mean length of 1785 base pair. Around 66.6% of unigenes were annotated by using various public databases and 5324 unigenes showed significant match in the KEGG database involved in 133 different pathways of plant metabolism. Further KEGG analysis resulted in identification of 336 unigenes involved in cardenolide biosynthesis. Tissue specific expression analysis of 30 putative transcripts involved in terpenoid, steroid and cardenolide pathways showed a positive correlation between metabolite and transcript accumulation. Wound stress elevated CG levels as well the levels of the putative transcripts involved in its biosynthetic pathways. This result further validated the involvement of identified transcripts in CGs biosynthesis. The identified transcripts will lay a substantial foundation for further research on metabolic engineering and regulation of cardiac glycosides biosynthesis pathway genes. PMID:27703261

  1. Reporter pathway analysis from transcriptome data: Metabolite-centric versus Reaction-centric approach

    PubMed Central

    Çakır, Tunahan

    2015-01-01

    A systems-based investigation of the effect of perturbations on metabolic machinery is crucial to elucidate the mechanism behind perturbations. One way to investigate the perturbation-induced changes within the cell metabolism is to focus on pathway-level effects. In this study, three different perturbation types (genetic, environmental and disease-based) are analyzed to compute a list of reporter pathways, metabolic pathways which are significantly affected from a perturbation. The most common omics data type, transcriptome, is used as an input to the bioinformatic analysis. The pathways are scored by two alternative approaches: by averaging the changes in the expression levels of the genes controlling the associated reactions (reaction-centric), and by averaging the changes in the associated metabolites which were scored based on the associated genes (metabolite-centric). The analysis reveals the superiority of the novel metabolite-centric approach over the commonly used reaction-centric approach since it is based on metabolites which better represent the cross-talk among different pathways, enabling a more global and realistic cataloguing of network-wide perturbation effects. PMID:26411587

  2. Car indoor air pollution - analysis of potential sources.

    PubMed

    Müller, Daniel; Klingelhöfer, Doris; Uibel, Stefanie; Groneberg, David A

    2011-12-16

    The population of industrialized countries such as the United States or of countries from the European Union spends approximately more than one hour each day in vehicles. In this respect, numerous studies have so far addressed outdoor air pollution that arises from traffic. By contrast, only little is known about indoor air quality in vehicles and influences by non-vehicle sources.Therefore the present article aims to summarize recent studies that address i.e. particulate matter exposure. It can be stated that although there is a large amount of data present for outdoor air pollution, research in the area of indoor air quality in vehicles is still limited. Especially, knowledge on non-vehicular sources is missing. In this respect, an understanding of the effects and interactions of i.e. tobacco smoke under realistic automobile conditions should be achieved in future.

  3. Bayesian Analysis of a Reduced-Form Air Quality Model

    EPA Science Inventory

    Numerical air quality models are being used for assessing emission control strategies for improving ambient pollution levels across the globe. This paper applies probabilistic modeling to evaluate the effectiveness of emission reduction scenarios aimed at lowering ground-level oz...

  4. Incorporating principal component analysis into air quality model evaluation

    EPA Science Inventory

    The efficacy of standard air quality model evaluation techniques is becoming compromised as the simulation periods continue to lengthen in response to ever increasing computing capacity. Accordingly, the purpose of this paper is to demonstrate a statistical approach called Princi...

  5. A qualitative analysis of future air combat with 'fire and forget' missiles

    NASA Technical Reports Server (NTRS)

    Shinar, J.; Davidovitz, A.

    1987-01-01

    A set of previous examples have demonstrated that the two-target game formulation is adequate for modeling air-to-air combat between two aggressively motivated fighter aircraft. The present paper describes such an engagement between two aircraft of different speed but equipped with the same 'fire and forget' type guided missiles. The results of the analysis suggest a new concept of air combat tactics for future scenarios.

  6. Comparative analysis of regulatory roles of P38 signaling pathway in 8 types liver cell during liver regeneration.

    PubMed

    Yang, Xianguang; Zhu, Lin; Zhao, Weiming; Shi, Yaohuang; He, Chuncui; Xu, Cunshuan

    2016-12-05

    P38MAPK signaling pathway was closely related to cell proliferation, apoptosis, cell differentiation, cell survival, cell death, and so on. However, the regulatory mechanism of P38MAPK signaling pathway in liver regeneration (LR) was unclear. In order to further reveal the roles of P38MAPK signaling pathway in rat liver regeneration, Ingenuity Pathway Analysis (IPA) software and related data sites were used to construct P38MAPK signaling pathway, and the pathway was confirmed by relevant documents literature. The expression changes of P38MAPK signaling pathway-related gene in eight type cells were further analyzed by Rat Genome 230 2.0 Array, and the results showed that 95 genes in P38MAPK signaling pathway had significant changes. H-cluster analysis showed that hepatocyte cell (HC), pit cell (PC), oval cell (OC) and biliary epithelial cell (BEC) are clustered together; and the same as Kupffer cell (KC), sinusoidal endothelial cell (SEC), dendritic cell (DC) and hepatic stellate cell (HSC). IPA software and expression analysis systematic explorer (EASE) were applied to functional enrichment analysis, and the results showed that P38MAPK signaling pathway was mainly involved in apoptosis, cell death, cell proliferation, cell survival, cell viability, activation, cell cycle progression, necrosis, synthesis of DNA and other physical activity during LR. In conclusion, P38MAPK signaling pathway regulated various physiological activities of LR through multiple signaling pathways.

  7. Cargo Logistics Airlift Systems Study (CLASS). Volume 1: Analysis of current air cargo system

    NASA Technical Reports Server (NTRS)

    Burby, R. J.; Kuhlman, W. H.

    1978-01-01

    The material presented in this volume is classified into the following sections; (1) analysis of current routes; (2) air eligibility criteria; (3) current direct support infrastructure; (4) comparative mode analysis; (5) political and economic factors; and (6) future potential market areas. An effort was made to keep the observations and findings relating to the current systems as objective as possible in order not to bias the analysis of future air cargo operations reported in Volume 3 of the CLASS final report.

  8. Identification of Novel Biomarkers in Seasonal Allergic Rhinitis by Combining Proteomic, Multivariate and Pathway Analysis

    PubMed Central

    Wang, Hui; Gottfries, Johan; Barrenäs, Fredrik; Benson, Mikael

    2011-01-01

    Background Glucocorticoids (GCs) play a key role in the treatment of seasonal allergic rhinitis (SAR). However, some patients show a low response to GC treatment. We hypothesized that proteins that correlated to discrimination between symptomatic high and low responders (HR and LR) to GC treatment might be regulated by GCs and therefore suitable as biomarkers for GC treatment. Methodology/Principal Findings We identified 953 nasal fluid proteins in symptomatic HR and LR with a LC MS/MS based-quantitative proteomics analysis and performed multivariate analysis to identify a combination of proteins that best separated symptomatic HR and LR. Pathway analysis showed that those proteins were most enriched in the acute phase response pathway. We prioritized candidate biomarkers for GC treatment based on the multivariate and pathway analysis. Next, we tested if those candidate biomarkers differed before and after GC treatment in nasal fluids from 40 patients with SAR using ELISA. Several proteins including ORM (P<0.0001), APOH (P<0.0001), FGA (P<0.01), CTSD (P<0.05) and SERPINB3 (P<0.05) differed significantly before and after GC treatment. Particularly, ORM (P<0.01), FGA (P<0.05) and APOH (P<0.01) that belonged to the acute phase response pathway decreased significantly in HR but not LR before and after GC treatment. Conclusions/Significance We identified several novel biomarkers for GC treatment response in SAR with combined proteomics, multivariate and pathway analysis. The analytical principles may be generally applicable to identify biomarkers in clinical studies of complex diseases. PMID:21887273

  9. Pathway Analysis of Proteomics Profiles in Rabies Infection: Towards Future Biomarkers?

    PubMed

    Mehta, Shraddha; Sreenivasamurthy, Sreelakshmi; Banerjee, Shefali; Mukherjee, Sandeepan; Prasad, Keshava; Chowdhary, Abhay

    2016-02-01

    Rabies is a zoonotic viral disease that invariably leads to fatal encephalitis, which can be prevented provided post-exposure prophylaxis is initiated timely. Ante-mortem diagnostic tests are inconclusive, and rabies is nontreatable once the clinical signs appear. A large number of host factors are responsible for the altered neuronal functions observed in rabies; however their precise role remains uninvestigated. We therefore used two-dimensional electrophoresis and mass spectrometry analysis to identify differentially expressed host proteins in an experimental murine model of rabies. We identified 143 proteins corresponding to 45 differentially expressed spots (p < 0.05) in neuronal tissues of Swiss albino mice in response to infection with neurovirulent rabies strains. Time series analyses revealed that a majority of the alterations occur at 4 to 6 days post infection, in particular affecting the host's cytoskeletal architecture. Extensive pathway analysis and protein interaction studies using the bioinformatic tools such as Ingenuity Pathway Analysis and STRING revealed novel pathways and molecules (e.g., protein ubiquitination) unexplored hitherto. Further activation/inhibition studies of these pathway molecular leads would be relevant to identify novel biomarkers and mechanism-based therapeutics for rabies, a disease that continues to severely impact global health.

  10. Elementary Vectors and Conformal Sums in Polyhedral Geometry and their Relevance for Metabolic Pathway Analysis

    PubMed Central

    Müller, Stefan; Regensburger, Georg

    2016-01-01

    A fundamental result in metabolic pathway analysis states that every flux mode can be decomposed into a sum of elementary modes. However, only a decomposition without cancelations is biochemically meaningful, since a reversible reaction cannot have different directions in the contributing elementary modes. This essential requirement has been largely overlooked by the metabolic pathway community. Indeed, every flux mode can be decomposed into elementary modes without cancelations. The result is an immediate consequence of a theorem by Rockafellar which states that every element of a linear subspace is a conformal sum (a sum without cancelations) of elementary vectors (support-minimal vectors). In this work, we extend the theorem, first to “subspace cones” and then to general polyhedral cones and polyhedra. Thereby, we refine Minkowski's and Carathéodory's theorems, two fundamental results in polyhedral geometry. We note that, in general, elementary vectors need not be support-minimal; in fact, they are conformally non-decomposable and form a unique minimal set of conformal generators. Our treatment is mathematically rigorous, but suitable for systems biologists, since we give self-contained proofs for our results and use concepts motivated by metabolic pathway analysis. In particular, we study cones defined by linear subspaces and nonnegativity conditions — like the flux cone — and use them to analyze general polyhedral cones and polyhedra. Finally, we review applications of elementary vectors and conformal sums in metabolic pathway analysis. PMID:27252734

  11. Methods of analysis for chemicals that disrupt cellular signaling pathways: risk assessment for potential endocrine disruptors.

    PubMed

    Umezawa, Yoshio; Ozawa, Takeaki; Sato, Moritoshi; Inadera, Hidekuni; Kaneko, Shuichi; Kunimoto, Manabu; Hashimoto, Shin-ichi

    2005-01-01

    Here we present a basic concept and several examples of methods of analysis for chemicals that disrupt cellular signaling pathways, in view of risk assessment for potential endocrine disrupting chemicals (EDCs). The key cellular signaling pathways include 1) ER/coactivator interaction, 2) AR translocation into the nucleus, 3) ER/NO/sGC/cGMP, 4) ER/Akt, 5) ER/Src, 6)ER/Src/Grb2, and 7) ER/Ca2+/CaM/CaMK pathways. These were visualized in relevant live cells using newly developed fluorescent and bioluminescent probes. Changes in cellular signals were thereby observed in nongenomic pathways of steroid hormones upon treatment of the target cells with steroid hormones and related chemicals. This method of analysis appears to be a rational approach to high-throughput prescreening (HTPS) of biohazardous chemicals, EDCs, in particular. Also described was the screening of gene expression by serial analysis of gene expression and gene chips upon applying EDCs to breast cancer cells, mouse livers, and human neuroblastoma NB-1 cells.

  12. Transcriptome Analysis of Manganese-deficient Chlamydomonas reinhardtii Provides Insight on the Chlorophyll Biosynthesis Pathway

    SciTech Connect

    Lockhart, Ainsley; Zvenigorodsky, Natasha; Pedraza, Mary Ann; Lindquist, Erika

    2011-08-11

    The biosynthesis of chlorophyll and other tetrapyrroles is a vital but poorly understood process. Recent genomic advances with the unicellular green algae Chlamydomonas reinhardtii have created opportunity to more closely examine the mechanisms of the chlorophyll biosynthesis pathway via transcriptome analysis. Manganese is a nutrient of interest for complex reactions because of its multiple stable oxidation states and role in molecular oxygen coordination. C. reinhardtii was cultured in Manganese-deplete Tris-acetate-phosphate (TAP) media for 24 hours and used to create cDNA libraries for sequencing using Illumina TruSeq technology. Transcriptome analysis provided intriguing insight on possible regulatory mechanisms in the pathway. Evidence supports similarities of GTR (Glutamyl-tRNA synthase) to its Chlorella vulgaris homolog in terms of Mn requirements. Data was also suggestive of Mn-related compensatory up-regulation for pathway proteins CHLH1 (Manganese Chelatase), GUN4 (Magnesium chelatase activating protein), and POR1 (Light-dependent protochlorophyllide reductase). Intriguingly, data suggests possible reciprocal expression of oxygen dependent CPX1 (coproporphyrinogen III oxidase) and oxygen independent CPX2. Further analysis using RT-PCR could provide compelling evidence for several novel regulatory mechanisms in the chlorophyll biosynthesis pathway.

  13. An analysis of trichloroethylene movement in groundwater at castle Air Force Base, California

    USGS Publications Warehouse

    Avon, L.; Bredehoeft, J.D.

    1989-01-01

    A trichloroethylene (TCE) plume has been identified in the groundwater under a U.S. Air Force Base in the Central Valley of California. An areal, two-dimensional numerical solute transport model indicates that the movement of TCE due to advection, dispersion, and linear sorption is simulated over a 25-year historic period. The model is used in several ways: (1) to estimate the extent of the plume; (2) to confirm the likely sources of contamination as suggested by a soil organic vapor survey of the site; and (3) to make predictions about future movement of the plume. Despite the noisy and incomplete data set, the model reproduces the general trends in contamination at a number of observation wells. The analysis indicates that soil organic vapor monitoring is an effective tool for identifying contaminant source locations. Leaky sewer pipes and underground tanks are the indicated pathways for TCE to have entered the groundwater system. The chemical mass balance indicates that a total of about 100 gallons of TCE - a relatively small amount of organic solvent - has created the observed groundwater plume. ?? 1989.

  14. Identification of Potential Novel Biomarkers and Signaling Pathways Related to Otitis Media Induced by Diesel Exhaust Particles Using Transcriptomic Analysis in an In Vivo System

    PubMed Central

    Kwon, Jee Young; Kim, Yeo Jin; Hun Kang, Seung; Jang, Won-Hee; Lee, Jun Ho; Seo, Myung-Whan; Song, Jae-Jun; Seo, Young Rok; Park, Moo Kyun

    2016-01-01

    Introduction Air pollutants are associated with inflammatory diseases such as otitis media (OM). Significantly higher incidence rates of OM are reported in regions with air pollution. Diesel exhaust particles (DEPs) comprise a major class of contaminants among numerous air pollutants, and they are characterized by a carbonic mixture of polycyclic aromatic hydrocarbons (PAHs), nitro-PAHs, and small amounts of sulfate, nitrate, metals and other trace elements. DEP exposure is a risk factor for inflammatory diseases. Our previous study identified potential biomarkers using gene expression microarray and pathway analyses in an in vitro system. Although in vitro investigations have been conducted to elucidate plausible biomarkers and molecular mechanisms related to DEP exposure, in vivo studies are necessary to identify the exact biological relevance regarding the incidence of OM caused by DEP exposure. In this study, we identified potential molecular biomarkers and pathways triggered by DEP exposure in a rodent model. Methods Transcriptomic analysis was employed to identify novel potential biomarkers in the middle ear of DEP-exposed mice. Results A total of 697 genes were differentially expressed in the DEP-exposed mice; 424 genes were upregulated and 273 downregulated. In addition, signaling pathways among the differentially expressed genes mediated by DEP exposure were predicted. Several key molecular biomarkers were identified including cholinergic receptor muscarinic 1 (CHRM1), erythropoietin (EPO), son of sevenless homolog 1 (SOS1), estrogen receptor 1 (ESR1), cluster of differentiation 4 (CD4) and interferon alpha-1 (IFNA1). Conclusions Our results shed light on the related cell processes and gene signaling pathways affected by DEP exposure. The identified biomarkers might be potential candidates for determining early diagnoses and effective treatment strategies for DEP-mediated disorders. PMID:27832168

  15. Parameters used in the environmental pathways (DESCARTES) and radiological dose (CIDER) modules of the Hanford Environmental Dose Reconstruction Integrated Codes (HEDRIC) for the air pathway

    SciTech Connect

    Snyder, S.F.; Farris, W.T.; Napier, B.A.; Ikenberry, T.A.; Gilbert, R.O.

    1992-09-01

    This letter report is a description of work performed for the Hanford Environmental Dose Reconstruction (HEDR) Project. The HEDR Project was established to estimate the radiation doses to individuals resulting from releases of radionuclides from the Hanford Site since 1944. This work is being done by staff at Battelle, Pacific Northwest Laboratories (Battelle) under a contract with the Centers for Disease Control (CDC) with technical direction provided by an independent Technical Steering Panel (TSP). The objective of this report is to-document the environmental accumulation and dose-assessment parameters that will be used to estimate the impacts of past Hanford Site airborne releases. During 1993, dose estimates made by staff at Battelle will be used by the Fred Hutchinson Cancer Research Center as part of the Hanford Thyroid Disease Study (HTDS). This document contains information on parameters that are specific to the airborne release of the radionuclide iodine-131. Future versions of this document will include parameter information pertinent to other pathways and radionuclides.

  16. The effect of long-range air mass transport pathways on PM10 and NO2 concentrations at urban and rural background sites in Ireland: Quantification using clustering techniques.

    PubMed

    Donnelly, Aoife A; Broderick, Brian M; Misstear, Bruce D

    2015-01-01

    The specific aims of this paper are to: (i) quantify the effects of various long range transport pathways nitrogen dioxide (NO2) and particulate matter with diameter less than 10μm (PM10) concentrations in Ireland and identify air mass movement corridors which may lead to incidences poor air quality for application in forecasting; (ii) compare the effects of such pathways at various sites; (iii) assess pathways associated with a period of decreased air quality in Ireland. The origin of and the regions traversed by an air mass 96h prior to reaching a receptor is modelled and k-means clustering is applied to create air-mass groups. Significant differences in air pollution levels were found between air mass cluster types at urban and rural sites. It was found that easterly or recirculated air masses lead to higher NO2 and PM10 levels with average NO2 levels varying between 124% and 239% of the seasonal mean and average PM10 levels varying between 103% and 199% of the seasonal mean at urban and rural sites. Easterly air masses are more frequent during winter months leading to higher overall concentrations. The span in relative concentrations between air mass clusters is highest at the rural site indicating that regional factors are controlling concentration levels. The methods used in this paper could be applied to assist in modelling and forecasting air quality based on long range transport pathways and forecast meteorology without the requirement for detailed emissions data over a large regional domain or the use of computationally demanding modelling techniques.

  17. Estimating pathway-specific contributions to biodegradation in aquifers based on dual isotope analysis: theoretical analysis and reactive transport simulations.

    PubMed

    Centler, Florian; Heße, Falk; Thullner, Martin

    2013-09-01

    At field sites with varying redox conditions, different redox-specific microbial degradation pathways contribute to total contaminant degradation. The identification of pathway-specific contributions to total contaminant removal is of high practical relevance, yet difficult to achieve with current methods. Current stable-isotope-fractionation-based techniques focus on the identification of dominant biodegradation pathways under constant environmental conditions. We present an approach based on dual stable isotope data to estimate the individual contributions of two redox-specific pathways. We apply this approach to carbon and hydrogen isotope data obtained from reactive transport simulations of an organic contaminant plume in a two-dimensional aquifer cross section to test the applicability of the method. To take aspects typically encountered at field sites into account, additional simulations addressed the effects of transverse mixing, diffusion-induced stable-isotope fractionation, heterogeneities in the flow field, and mixing in sampling wells on isotope-based estimates for aerobic and anaerobic pathway contributions to total contaminant biodegradation. Results confirm the general applicability of the presented estimation method which is most accurate along the plume core and less accurate towards the fringe where flow paths receive contaminant mass and associated isotope signatures from the core by transverse dispersion. The presented method complements the stable-isotope-fractionation-based analysis toolbox. At field sites with varying redox conditions, it provides a means to identify the relative importance of individual, redox-specific degradation pathways.

  18. Bioinformatics Analysis Reveals MicroRNAs Regulating Biological Pathways in Exercise-Induced Cardiac Physiological Hypertrophy

    PubMed Central

    Xu, Jiahong; Liu, Yang; Xie, Yuan

    2017-01-01

    Exercise-induced physiological cardiac hypertrophy is generally considered to be a type of adaptive change after exercise training and is beneficial for cardiovascular diseases. This study aims at investigating exercise-regulated microRNAs (miRNAs) and their potential biological pathways. Here, we collected 23 miRNAs from 8 published studies. MirPath v.3 from the DIANA tools website was used to execute the analysis, and TargetScan was used to predict the target genes. Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) analyses were performed to identify potential pathways and functional annotations associated with exercise-induced physiological cardiac hypertrophy. Various miRNA targets and molecular pathways, such as Fatty acid elongation, Arrhythmogenic right ventricular cardiomyopathy (ARVC), and ECM-receptor interaction, were identified. This study could prompt the understanding of the regulatory mechanisms underlying exercise-induced physiological cardiac hypertrophy. PMID:28286759

  19. Bioinformatics Analysis Reveals MicroRNAs Regulating Biological Pathways in Exercise-Induced Cardiac Physiological Hypertrophy.

    PubMed

    Xu, Jiahong; Liu, Yang; Xie, Yuan; Zhao, Cuimei; Wang, Hongbao

    2017-01-01

    Exercise-induced physiological cardiac hypertrophy is generally considered to be a type of adaptive change after exercise training and is beneficial for cardiovascular diseases. This study aims at investigating exercise-regulated microRNAs (miRNAs) and their potential biological pathways. Here, we collected 23 miRNAs from 8 published studies. MirPath v.3 from the DIANA tools website was used to execute the analysis, and TargetScan was used to predict the target genes. Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) analyses were performed to identify potential pathways and functional annotations associated with exercise-induced physiological cardiac hypertrophy. Various miRNA targets and molecular pathways, such as Fatty acid elongation, Arrhythmogenic right ventricular cardiomyopathy (ARVC), and ECM-receptor interaction, were identified. This study could prompt the understanding of the regulatory mechanisms underlying exercise-induced physiological cardiac hypertrophy.

  20. Transcriptome Pathway Analysis of Pathological and Physiological Aldosterone-Producing Human Tissues

    PubMed Central

    Zhou, Junhua; Lam, Brian; Neogi, Sudeshna G.; Yeo, Giles S.H.; Brown, Morris J.

    2016-01-01

    Primary aldosteronism is present in ≈10% of hypertensives. We previously performed a microarray assay on aldosterone-producing adenomas and their paired zona glomerulosa and fasciculata. Confirmation of top genes validated the study design and functional experiments of zona glomerulosa selective genes established the role of the encoded proteins in aldosterone regulation. In this study, we further analyzed our microarray data using AmiGO 2 for gene ontology enrichment and Ingenuity Pathway Analysis to identify potential biological processes and canonical pathways involved in pathological and physiological aldosterone regulation. Genes differentially regulated in aldosterone-producing adenoma and zona glomerulosa were associated with steroid metabolic processes gene ontology terms. Terms related to the Wnt signaling pathway were enriched in zona glomerulosa only. Ingenuity Pathway Analysis showed "NRF2-mediated oxidative stress response pathway" and "LPS (lipopolysaccharide)/IL-1 (interleukin-1)–mediated inhibition of RXR (retinoid X receptor) function" were affected in both aldosterone-producing adenoma and zona glomerulosa with associated genes having up to 21- and 8-fold differences, respectively. Comparing KCNJ5-mutant aldosterone-producing adenoma, zona glomerulosa, and zona fasciculata samples with wild-type samples, 138, 56, and 59 genes were differentially expressed, respectively (fold-change >2; P<0.05). ACSS3, encoding the enzyme that synthesizes acetyl-CoA, was the top gene upregulated in KCNJ5-mutant aldosterone-producing adenoma compared with wild-type. NEFM, a gene highly upregulated in zona glomerulosa, was upregulated in KCNJ5 wild-type aldosterone-producing adenomas. NR4A2, the transcription factor for aldosterone synthase, was highly expressed in zona fasciculata adjacent to a KCNJ5-mutant aldosterone-producing adenoma. Further interrogation of these genes and pathways could potentially provide further insights into the pathology of primary

  1. Identification of key pathways and genes in colorectal cancer using bioinformatics analysis.

    PubMed

    Liang, Bin; Li, Chunning; Zhao, Jianying

    2016-10-01

    Colorectal cancer (CRC) is the most common malignant tumor of digestive system. The aim of this study was to identify gene signatures during CRC and uncover their potential mechanisms. The gene expression profiles of GSE21815 were downloaded from GEO database. The GSE21815 dataset contained 141 samples, including 132 CRC and 9 normal colon epitheliums. The gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes pathway (KEGG) enrichment analyses were performed, and protein-protein interaction (PPI) network of the differentially expressed genes (DEGs) was constructed by Cytoscape software. In total, 3500 DEGs were identified in CRC, including 1370 up-regulated genes and 2130 down-regulated genes. GO analysis results showed that up-regulated DEGs were significantly enriched in biological processes (BP), including cell cycle, cell division, and cell proliferation; the down-regulated DEGs were significantly enriched in biological processes, including immune response, intracellular signaling cascade and defense response. KEGG pathway analysis showed the up-regulated DEGs were enriched in cell cycle and DNA replication, while the down-regulated DEGs were enriched in drug metabolism, metabolism of xenobiotics by cytochrome P450, and retinol metabolism pathways. The top 10 hub genes, GNG2, AGT, SAA1, ADCY5, LPAR1, NMU, IL8, CXCL12, GNAI1, and CCR2 were identified from the PPI network, and sub-networks revealed these genes were involved in significant pathways, including G protein-coupled receptors signaling pathway, gastrin-CREB signaling pathway via PKC and MAPK, and extracellular matrix organization. In conclusion, the present study indicated that the identified DEGs and hub genes promote our understanding of the molecular mechanisms underlying the development of CRC, and might be used as molecular targets and diagnostic biomarkers for the treatment of CRC.

  2. Differentially expressed genes and interacting pathways in bladder cancer revealed by bioinformatic analysis.

    PubMed

    Shen, Yinzhou; Wang, Xuelei; Jin, Yongchao; Lu, Jiasun; Qiu, Guangming; Wen, Xiaofei

    2014-10-01

    The goal of this study was to identify cancer-associated differentially expressed genes (DEGs), analyze their biological functions and investigate the mechanism(s) of cancer occurrence and development, which may provide a theoretical foundation for bladder cancer (BCa) therapy. We downloaded the mRNA expression profiling dataset GSE13507 from the Gene Expression Omnibus database; the dataset includes 165 BCa and 68 control samples. T‑tests were used to identify DEGs. To further study the biological functions of the identified DEGs, we performed a Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. Next, we built a network of potentially interacting pathways to study the synergistic relationships among DEGs. A total of 12,105 genes were identified as DEGs, of which 5,239 were upregulated and 6,866 were downregulated in BCa. The DEGs encoding activator protein 1 (AP-1), nuclear factor of activated T-cells (NFAT) proteins, nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB) and interleukin (IL)-10 were revealed to participate in the significantly enriched immune pathways that were downregulated in BCa. KEGG enrichment analysis revealed 7 significantly upregulated and 47 significantly downregulated pathways enriched among the DEGs. We found a crosstalk interaction among a total of 44 pathways in the network of BCa-affected pathways. In conclusion, our results show that BCa involves dysfunctions in multiple systems. Our study is expected to pave ways for immune and inflammatory research and provide molecular insights for cancer therapy.

  3. Analysis of extensive air showers with the hybrid code SENECA

    NASA Astrophysics Data System (ADS)

    Ortiz, Jeferson A.; de Souza, Vitor; Medina-Tanco, Gustavo

    The ultrahigh energy tail of the cosmic ray spectrum has been explored with unprecedented detail. For this reason, new experiments are exerting a severe pressure on extensive air shower modeling. Detailed fast codes are in need in order to extract and understand the richness of information now available. In this sense we explore the potential of SENECA, an efficient hybrid tridimensional simulation code, as a valid practical alternative to full Monte Carlo simulations of extensive air showers generated by ultrahigh energy cosmic rays. We discuss the influence of this approach on the main longitudinal characteristics of proton, iron nucleus and gamma induced air showers for different hadronic interaction models. We also show the comparisons of our predictions with those of CORSIKA code.

  4. Analysis of the Chinese provincial air transportation network

    NASA Astrophysics Data System (ADS)

    Du, Wen-Bo; Liang, Bo-Yuan; Hong, Chen; Lordan, Oriol

    2017-01-01

    The air transportation system is of a great impact on the economy and globalization of a country. In this paper, we analyze the Chinese air transportation network (ATN) from a provincial perspective via the complex network framework, where all airports located in one province are abstracted as a single node and flights between two provinces are denoted by a link. The results show that the network exhibits small-world property, homogeneous structure and disassortative mixing. The variation of the flight flow within 24 h is investigated and an obvious tide phenomenon is found in the dynamics of Chinese provincial ATN for high output level of tertiary industry. Our work will offer a novel approach for understanding the characteristic of the Chinese air transportation network.

  5. Cloning and Expression Analysis of MEP Pathway Enzyme-encoding Genes in Osmanthus fragrans

    PubMed Central

    Xu, Chen; Li, Huogeng; Yang, Xiulian; Gu, Chunsun; Mu, Hongna; Yue, Yuanzheng; Wang, Lianggui

    2016-01-01

    The 2-C-methyl-d-erythritol 4-phosphate (MEP) pathway is responsible for the biosynthesis of many crucial secondary metabolites, such as carotenoids, monoterpenes, plastoquinone, and tocopherols. In this study, we isolated and identified 10 MEP pathway genes in the important aromatic plant sweet osmanthus (Osmanthus fragrans). Multiple sequence alignments revealed that 10 MEP pathway genes shared high identities with other reported proteins. The genes showed distinctive expression profiles in various tissues, or at different flower stages and diel time points. The qRT-PCR results demonstrated that these genes were highly expressed in inflorescences, which suggested a tissue-specific transcript pattern. Our results also showed that OfDXS1, OfDXS2, and OfHDR1 had a clear diurnal oscillation pattern. The isolation and expression analysis provides a strong foundation for further research on the MEP pathway involved in gene function and molecular evolution, and improves our understanding of the molecular mechanism underlying this pathway in plants. PMID:27690108

  6. Transcriptomic analysis in the developing zebrafish embryo after compound exposure: individual gene expression and pathway regulation.

    PubMed

    Hermsen, Sanne A B; Pronk, Tessa E; van den Brandhof, Evert-Jan; van der Ven, Leo T M; Piersma, Aldert H

    2013-10-01

    The zebrafish embryotoxicity test is a promising alternative assay for developmental toxicity. Classically, morphological assessment of the embryos is applied to evaluate the effects of compound exposure. However, by applying differential gene expression analysis the sensitivity and predictability of the test may be increased. For defining gene expression signatures of developmental toxicity, we explored the possibility of using gene expression signatures of compound exposures based on commonly expressed individual genes as well as based on regulated gene pathways. Four developmental toxic compounds were tested in concentration-response design, caffeine, carbamazepine, retinoic acid and valproic acid, and two non-embryotoxic compounds, d-mannitol and saccharin, were included. With transcriptomic analyses we were able to identify commonly expressed genes, which were mostly development related, after exposure to the embryotoxicants. We also identified gene pathways regulated by the embryotoxicants, suggestive of their modes of action. Furthermore, whereas pathways may be regulated by all compounds, individual gene expression within these pathways can differ for each compound. Overall, the present study suggests that the use of individual gene expression signatures as well as pathway regulation may be useful starting points for defining gene biomarkers for predicting embryotoxicity.

  7. Computational Systems Bioinformatics and Bioimaging for Pathway Analysis and Drug Screening

    PubMed Central

    Zhou, Xiaobo; Wong, Stephen T. C.

    2009-01-01

    The premise of today’s drug development is that the mechanism of a disease is highly dependent upon underlying signaling and cellular pathways. Such pathways are often composed of complexes of physically interacting genes, proteins, or biochemical activities coordinated by metabolic intermediates, ions, and other small solutes and are investigated with molecular biology approaches in genomics, proteomics, and metabonomics. Nevertheless, the recent declines in the pharmaceutical industry’s revenues indicate such approaches alone may not be adequate in creating successful new drugs. Our observation is that combining methods of genomics, proteomics, and metabonomics with techniques of bioimaging will systematically provide powerful means to decode or better understand molecular interactions and pathways that lead to disease and potentially generate new insights and indications for drug targets. The former methods provide the profiles of genes, proteins, and metabolites, whereas the latter techniques generate objective, quantitative phenotypes correlating to the molecular profiles and interactions. In this paper, we describe pathway reconstruction and target validation based on the proposed systems biologic approach and show selected application examples for pathway analysis and drug screening. PMID:20011613

  8. Analysis of Sensitive CO2 Pathways and Genes Related to Carbon Uptake and Accumulation in Chlamydomonas reinhardtii through Genomic Scale Modeling and Experimental Validation

    PubMed Central

    Winck, Flavia V.; Melo, David O. Páez; Riaño-Pachón, Diego M.; Martins, Marina C. M.; Caldana, Camila; Barrios, Andrés F. González

    2016-01-01

    The development of microalgae sustainable applications needs better understanding of microalgae biology. Moreover, how cells coordinate their metabolism toward biomass accumulation is not fully understood. In this present study, flux balance analysis (FBA) was performed to identify sensitive metabolic pathways of Chlamydomonas reinhardtii under varied CO2 inputs. The metabolic network model of Chlamydomonas was updated based on the genome annotation data and sensitivity analysis revealed CO2 sensitive reactions. Biological experiments were performed with cells cultivated at 0.04% (air), 2.5, 5, 8, and 10% CO2 concentration under controlled conditions and cell growth profiles and biomass content were measured. Pigments, lipids, proteins, and starch were further quantified for the reference low (0.04%) and high (10%) CO2 conditions. The expression level of candidate genes of sensitive reactions was measured and validated by quantitative real time PCR. The sensitive analysis revealed mitochondrial compartment as the major affected by changes on the CO2 concentrations and glycolysis/gluconeogenesis, glyoxylate, and dicarboxylate metabolism among the affected metabolic pathways. Genes coding for glycerate kinase (GLYK), glycine cleavage system, H-protein (GCSH), NAD-dependent malate dehydrogenase (MDH3), low-CO2 inducible protein A (LCIA), carbonic anhydrase 5 (CAH5), E1 component, alpha subunit (PDC3), dual function alcohol dehydrogenase/acetaldehyde dehydrogenase (ADH1), and phosphoglucomutase (GPM2), were defined, among other genes, as sensitive nodes in the metabolic network simulations. These genes were experimentally responsive to the changes in the carbon fluxes in the system. We performed metabolomics analysis using mass spectrometry validating the modulation of carbon dioxide responsive pathways and metabolites. The changes on CO2 levels mostly affected the metabolism of amino acids found in the photorespiration pathway. Our updated metabolic network was

  9. Analysis of Sensitive CO2 Pathways and Genes Related to Carbon Uptake and Accumulation in Chlamydomonas reinhardtii through Genomic Scale Modeling and Experimental Validation.

    PubMed

    Winck, Flavia V; Melo, David O Páez; Riaño-Pachón, Diego M; Martins, Marina C M; Caldana, Camila; Barrios, Andrés F González

    2016-01-01

    The development of microalgae sustainable applications needs better understanding of microalgae biology. Moreover, how cells coordinate their metabolism toward biomass accumulation is not fully understood. In this present study, flux balance analysis (FBA) was performed to identify sensitive metabolic pathways of Chlamydomonas reinhardtii under varied CO2 inputs. The metabolic network model of Chlamydomonas was updated based on the genome annotation data and sensitivity analysis revealed CO2 sensitive reactions. Biological experiments were performed with cells cultivated at 0.04% (air), 2.5, 5, 8, and 10% CO2 concentration under controlled conditions and cell growth profiles and biomass content were measured. Pigments, lipids, proteins, and starch were further quantified for the reference low (0.04%) and high (10%) CO2 conditions. The expression level of candidate genes of sensitive reactions was measured and validated by quantitative real time PCR. The sensitive analysis revealed mitochondrial compartment as the major affected by changes on the CO2 concentrations and glycolysis/gluconeogenesis, glyoxylate, and dicarboxylate metabolism among the affected metabolic pathways. Genes coding for glycerate kinase (GLYK), glycine cleavage system, H-protein (GCSH), NAD-dependent malate dehydrogenase (MDH3), low-CO2 inducible protein A (LCIA), carbonic anhydrase 5 (CAH5), E1 component, alpha subunit (PDC3), dual function alcohol dehydrogenase/acetaldehyde dehydrogenase (ADH1), and phosphoglucomutase (GPM2), were defined, among other genes, as sensitive nodes in the metabolic network simulations. These genes were experimentally responsive to the changes in the carbon fluxes in the system. We performed metabolomics analysis using mass spectrometry validating the modulation of carbon dioxide responsive pathways and metabolites. The changes on CO2 levels mostly affected the metabolism of amino acids found in the photorespiration pathway. Our updated metabolic network was

  10. The Analysis of PPM Levels of Gases in Air by Photoionization Mass Spectrometry

    ERIC Educational Resources Information Center

    Driscoll, John N.; Warneck, Peter

    1973-01-01

    Discusses analysis of trace gases in air by photoionization mass spectrometer. It is shown that the necessary sensitivity can be obtained by eliminating the UV monochromator and using direct ionization with a hydrogen light source. (JP)

  11. Applications of principal component analysis to breath air absorption spectra profiles classification

    NASA Astrophysics Data System (ADS)

    Kistenev, Yu. V.; Shapovalov, A. V.; Borisov, A. V.; Vrazhnov, D. A.; Nikolaev, V. V.; Nikiforova, O. Y.

    2015-12-01

    The results of numerical simulation of application principal component analysis to absorption spectra of breath air of patients with pulmonary diseases are presented. Various methods of experimental data preprocessing are analyzed.

  12. Genome-Wide Analysis of the Lysine Biosynthesis Pathway Network during Maize Seed Development

    PubMed Central

    Liu, Yuwei; Xie, Shaojun; Yu, Jingjuan

    2016-01-01

    Lysine is one of the most limiting essential amino acids for humans and livestock. The nutritional value of maize (Zea mays L.) is reduced by its poor lysine content. To better understand the lysine biosynthesis pathway in maize seed, we conducted a genome-wide analysis of the genes involved in lysine biosynthesis. We identified lysine biosynthesis pathway genes (LBPGs) and investigated whether a diaminopimelate pathway variant exists in maize. We analyzed two genes encoding the key enzyme dihydrodipicolinate synthase, and determined that they contribute differently to lysine synthesis during maize seed development. A coexpression network of LBPGs was constructed using RNA-sequencing data from 21 developmental stages of B73 maize seed. We found a large set of genes encoding ribosomal proteins, elongation factors and zein proteins that were coexpressed with LBPGs. The coexpressed genes were enriched in cellular metabolism terms and protein related terms. A phylogenetic analysis of the LBPGs from different plant species revealed different relationships. Additionally, six transcription factor (TF) families containing 13 TFs were identified as the Hub TFs of the LBPGs modules. Several expression quantitative trait loci of LBPGs were also identified. Our results should help to elucidate the lysine biosynthesis pathway network in maize seed. PMID:26829553

  13. Systematic proteomic analysis of human hepotacellular carcinoma cells reveals molecular pathways and networks involved in metastasis.

    PubMed

    Yu, Yanyan; Shen, Huali; Yu, Hongxiu; Zhong, Fan; Zhang, Yang; Zhang, Chen; Zhao, Jian; Li, Hong; Chen, Jie; Liu, Yinkun; Yang, Pengyuan

    2011-06-01

    Systematic proteomic studying of the mechanism of hepatocellular carcinoma (HCC) metastasis remains challenging. We performed comparative proteomic and pathway analysis of four human metastatic HCC cell lines to identify metastasis-associated proteins. These HCC cell lines had a similar genetic background but with an increasing potential of metastasis. Using a combination of two dimensional electrophoresis (2-DE) and MALDI-TOF mass spectrometry, a total of 125 proteins and their post-translational modification forms or isoforms were found to be differentially expressed in the cell lines. Among them, 29 were gradually up-regulated whereas 17 were down-regulated with increasing metastatic potential. Instead of a traditional single-gene readout, global bioinformatics analysis was carried out, which revealed that the glycolysis pathway was the most significantly enriched pathway. The heat shock proteins (HSPs) centered and NF-kappaB centered networks were also enriched in the result, which may imply the key function of inflaming on metastasis. Meanwhile, knockdown of HDGF, an up-regulated protein and a target of NF-kappaB, induced cell apoptosis in the metastatic HCC cells. This work provides a demonstration that a combination of bioinformatics and comparative proteomics can help in finding out potential biomarkers associated with HCC metastasis on the level of pathways.

  14. Analysis of Polygala tenuifolia Transcriptome and Description of Secondary Metabolite Biosynthetic Pathways by Illumina Sequencing

    PubMed Central

    Tian, Hongling; Xu, Xiaoshuang; Zhang, Fusheng; Wang, Yaoqin; Guo, Shuhong; Qin, Xuemei; Du, Guanhua

    2015-01-01

    Radix polygalae, the dried roots of Polygala tenuifolia and P. sibirica, is one of the most well-known traditional Chinese medicinal plants. Radix polygalae contains various saponins, xanthones, and oligosaccharide esters and these compounds are responsible for several pharmacological properties. To provide basic breeding information, enhance molecular biological analysis, and determine secondary metabolite biosynthetic pathways of P. tenuifolia, we applied Illumina sequencing technology and de novo assembly. We also applied this technique to gain an overview of P. tenuifolia transcriptome from samples with different years. Using Illumina sequencing, approximately 67.2% of unique sequences were annotated by basic local alignment search tool similarity searches against public sequence databases. We classified the annotated unigenes by using Nr, Nt, GO, COG, and KEGG databases compared with NCBI. We also obtained many candidates CYP450s and UGTs by the analysis of genes in the secondary metabolite biosynthetic pathways, including putative terpenoid backbone and phenylpropanoid biosynthesis pathway. With this transcriptome sequencing, future genetic and genomics studies related to the molecular mechanisms associated with the chemical composition of P. tenuifolia may be improved. Genes involved in the enrichment of secondary metabolite biosynthesis-related pathways could enhance the potential applications of P. tenuifolia in pharmaceutical industries. PMID:26543847

  15. Pathway Analysis of Seven Common Diseases Assessed by Genome-Wide Association

    PubMed Central

    Torkamani, Ali; Topol, Eric J.; Schork, Nicholas J.

    2008-01-01

    Recent genome wide association studies (GWAS) have identified DNA sequence variations that exhibit unequivocal statistical associations with many common chronic diseases. However, the vast majority of these studies identified variations that explain only a very small fraction of disease burden in the population at large, suggesting that other factors, such as multiple rare or low-penetrance variations and interacting environmental factors, are major contributors to disease susceptibility. Identifying multiple low penetrance variations (or ‘polygenes’) contributing to disease susceptibility will be difficult. We present a pathway analysis approach to characterizing the likely polygenic basis of seven common diseases using the Wellcome Trust Case Control Consortium (WTCCC) GWAS results. We identify numerous pathways implicated in disease predisposition that would have not been revealed using standard single-locus GWAS statistical analysis criteria. Many of these pathways have long been assumed to contain polymorphic genes that lead to disease predisposition. Additionally, we analyze the genetic relationships between the seven diseases, and based upon similarities with respect to the associated genes and pathways affected in each, propose a new way of categorizing the diseases. PMID:18722519

  16. Air-to-Ground Fratricide Reduction Technology: An Analysis

    DTIC Science & Technology

    2005-01-01

    Jennifer, and my children, Dean and Eden , for their patience and support during this long project. iv EXECUTIVE SUMMARY Title: Air-to...Fire.” Military Intelligence Professional Bulletin, March 2004, 15. URL: http://infoweb.newsbank.com. Accessed 4 September 2004. Cline, Bobby

  17. Analysis of Air Force Civil Engineering Strategic Planning

    DTIC Science & Technology

    2003-06-01

    Several organizations within the Department of Defense, including the Air Force Civil Engineer, are actively engaged in strategic planning in an...effort to create a roadmap for future capabilities and performance. The objective of this research was to analyze the strategic planning process of the

  18. An analysis of short haul air passenger demand, volume 2

    NASA Technical Reports Server (NTRS)

    Blumer, T. P.; Swan, W. M.

    1978-01-01

    Several demand models for short haul air travel are proposed and calibrated on pooled data. The models are designed to predict demand and analyze some of the motivating phenomena behind demand generation. In particular, an attempt is made to include the effects of competing modes and of alternate destinations. The results support three conclusions: (1) the auto mode is the air mode's major competitor; (2) trip time is an overriding factor in intermodal competition, with air fare at its present level appearing unimportant to the typical short haul air traveler; and (3) distance appears to underly several demand generating phenomena, and therefore, must be considered very carefully to any intercity demand model. It may be the cause of the wide range of fare elasticities reported by researchers over the past 15 years. A behavioral demand model is proposed and calibrated. It combines the travel generating effects of income and population, the effects of modal split, the sensitivity of travel to price and time, and the effect of alternative destinations satisfying the trip purpose.

  19. Performance testing and analysis of vertical ambient air vaporizers

    NASA Astrophysics Data System (ADS)

    Pandey, A. S.; Singh, V. N.; Shah, M. I.; Acharya, D. V.

    2017-02-01

    Ambient air vaporizers are used to regasify cryogenic liquids at extremely low temperature (below -153°C). Frost formation occurs on it due to large temperature difference between ambient air and cryogenic fluid. Frosting induces additional load on equipment and reduces its heat transfer effectiveness. Hence, mechanical and thermal design of vaporizers account for frosting. An experimental set-up has been designed and effects of flow rate and ground clearance on the performance of ambient air vaporizers are evaluated. The flow rate is increased from the rated capacity of 500 Nm3/h to 640 Nm3/h and ground clearance is reduced from 500 mm to 175 mm. The above variations reduce the time duration for which gaseous nitrogen is delivered at temperature higher than 10.1°C (desired). Hence duty cycle reduces from eight hours to five hours. The other factors affecting performance such as fin configuration, fluid type, fluid pressure, intermittent flow nature and climatic conditions are assumed to be constant over the test duration. The decrement in outlet gas temperature (from 38 °C to 10.1°C) with corresponding increment in frost thickness leads to deterioration of performance of ambient air vaporizers.

  20. Sensitivity Analysis for Atmospheric Infrared Sounder (AIRS) CO2 Retrieval

    NASA Technical Reports Server (NTRS)

    Gat, Ilana

    2012-01-01

    The Atmospheric Infrared Sounder (AIRS) is a thermal infrared sensor able to retrieve the daily atmospheric state globally for clear as well as partially cloudy field-of-views. The AIRS spectrometer has 2378 channels sensing from 15.4 micrometers to 3.7 micrometers, of which a small subset in the 15 micrometers region has been selected, to date, for CO2 retrieval. To improve upon the current retrieval method, we extended the retrieval calculations to include a prior estimate component and developed a channel ranking system to optimize the channels and number of channels used. The channel ranking system uses a mathematical formalism to rapidly process and assess the retrieval potential of large numbers of channels. Implementing this system, we identifed a larger optimized subset of AIRS channels that can decrease retrieval errors and minimize the overall sensitivity to other iridescent contributors, such as water vapor, ozone, and atmospheric temperature. This methodology selects channels globally by accounting for the latitudinal, longitudinal, and seasonal dependencies of the subset. The new methodology increases accuracy in AIRS CO2 as well as other retrievals and enables the extension of retrieved CO2 vertical profiles to altitudes ranging from the lower troposphere to upper stratosphere. The extended retrieval method for CO2 vertical profile estimation using a maximum-likelihood estimation method. We use model data to demonstrate the beneficial impact of the extended retrieval method using the new channel ranking system on CO2 retrieval.

  1. The analysis of a generic air-to-air missile simulation model

    NASA Technical Reports Server (NTRS)

    Kaplan, Joseph A.; Chappell, Alan R.; Mcmanus, John W.

    1994-01-01

    A generic missile model was developed to evaluate the benefits of using a dynamic missile fly-out simulation system versus a static missile launch envelope system for air-to-air combat simulation. This paper examines the performance of a launch envelope model and a missile fly-out model. The launch envelope model bases its probability of killing the target aircraft on the target aircraft's position at the launch time of the weapon. The benefits gained from a launch envelope model are the simplicity of implementation and the minimal computational overhead required. A missile fly-out model takes into account the physical characteristics of the missile as it simulates the guidance, propulsion, and movement of the missile. The missile's probability of kill is based on the missile miss distance (or the minimum distance between the missile and the target aircraft). The problems associated with this method of modeling are a larger computational overhead, the additional complexity required to determine the missile miss distance, and the additional complexity of determining the reason(s) the missile missed the target. This paper evaluates the two methods and compares the results of running each method on a comprehensive set of test conditions.

  2. Comparative In silico Analysis of Butyrate Production Pathways in Gut Commensals and Pathogens

    PubMed Central

    Anand, Swadha; Kaur, Harrisham; Mande, Sharmila S.

    2016-01-01

    Biosynthesis of butyrate by commensal bacteria plays a crucial role in maintenance of human gut health while dysbiosis in gut microbiome has been linked to several enteric disorders. Contrastingly, butyrate shows cytotoxic effects in patients with oral diseases like periodontal infections and oral cancer. In addition to these host associations, few syntrophic bacteria couple butyrate degradation with sulfate reduction and methane production. Thus, it becomes imperative to understand the distribution of butyrate metabolism pathways and delineate differences in substrate utilization between pathogens and commensals. The bacteria utilize four pathways for butyrate production with different initial substrates (Pyruvate, 4-aminobutyrate, Glutarate and Lysine) which follow a polyphyletic distribution. A comprehensive mining of complete/draft bacterial genomes indicated conserved juxtaposed genomic arrangement in all these pathways. This gene context information was utilized for an accurate annotation of butyrate production pathways in bacterial genomes. Interestingly, our analysis showed that inspite of a beneficial impact of butyrate in gut, not only commensals, but a few gut pathogens also possess butyrogenic pathways. The results further illustrated that all the gut commensal bacteria (Faecalibacterium, Roseburia, Butyrivibrio, and commensal species of Clostridia etc) ferment pyruvate for butyrate production. On the contrary, the butyrogenic gut pathogen Fusobacterium utilizes different amino acid metabolism pathways like those for Glutamate (4-aminobutyrate and Glutarate) and Lysine for butyrogenesis which leads to a concomitant release of harmful by-products like ammonia in the process. The findings in this study indicate that commensals and pathogens in gut have divergently evolved to produce butyrate using distinct pathways. No such evolutionary selection was observed in oral pathogens (Porphyromonas and Filifactor) which showed presence of pyruvate as well as

  3. Pathway-based Genome-Wide Association Analysis Identified the Importance of EphrinA-EphR pathway for Femoral Neck Bone Geometry

    PubMed Central

    Chen, Yuan; Xiong, Dong-Hai; Guo, Yan-Fang; Pan, Feng; Zhou, Qi; Zhang, Feng; Deng, Hong-Wen

    2009-01-01

    Femoral neck (FN) bone geometry is an important predictor of bone strength with high heritability. Previous studies have revealed certain candidate genes for FN bone geometry. However, the majority of the underlying genetic factors remain to be discovered. In this study, pathway-based genome-wide association analysis was performed to explore the joint effects of genes within biological pathways on FN bone geometry variations in a cohort of 1,000 unrelated U.S. whites. Nominal significant associations (nominal p value < 0.05) were observed between 76 pathways and a key FN bone geometry variable - section modulus (Z), biomechanically indicative of bone strength subject to bending. Among them, EphrinA-EphR pathway was most significantly associated with FN Z even after multiple testing adjustments (pFWER value = 0.035). The association of EphrinA-EphR pathway with FN Z was also observed in an independent sample from Framingham Osteoporosis Study. Overall, these results suggest the significant genetic contribution of EphrinA-EphR pathway to femoral neck bone geometry. PMID:19786129

  4. Haplotype association analysis of genes within the WNT signalling pathways in diabetic nephropathy

    PubMed Central

    2013-01-01

    Background Renal interstitial fibrosis and glomerular sclerosis are hallmarks of diabetic nephropathy (DN) and several studies have implicated members of the WNT pathways in these pathological processes. This study comprehensively examined common genetic variation within the WNT pathway for association with DN. Methods Genes within the WNT pathways were selected on the basis of nominal significance and consistent direction of effect in the GENIE meta-analysis dataset. Common SNPs and common haplotypes were examined within the selected WNT pathway genes in a white population with type 1 diabetes, discordant for DN (cases: n = 718; controls: n = 749). SNPs were genotyped using Sequenom or Taqman assays. Association analyses were performed using PLINK, to compare allele and haplotype frequencies in cases and controls. Correction for multiple testing was performed by either permutation testing or using false discovery rate. Results A logistic regression model including collection centre, duration of diabetes, and average HbA1c as covariates highlighted three SNPs in GSK3B (rs17810235, rs17471, rs334543), two in DAAM1 (rs1253192, rs1252906) and one in NFAT5 (rs17297207) as being significantly (P < 0.05) associated with DN, however these SNPs did not remain significant after correction for multiple testing. Logistic regression of haplotypes, with ESRD as the outcome, and pairwise interaction analyses did not yield any significant results after correction for multiple testing. Conclusions These results indicate that both common SNPs and common haplotypes of WNT pathway genes are not strongly associated with DN. However, this does not completely exclude these or the WNT pathways from association with DN, as unidentified rare genetic or copy number variants could still contribute towards the genetic architecture of DN. PMID:23777469

  5. Parallel labeling experiments for pathway elucidation and (13)C metabolic flux analysis.

    PubMed

    Antoniewicz, Maciek R

    2015-12-01

    Metabolic pathway models provide the foundation for quantitative studies of cellular physiology through the measurement of intracellular metabolic fluxes. For model organisms metabolic models are well established, with many manually curated genome-scale model reconstructions, gene knockout studies and stable-isotope tracing studies. However, for non-model organisms a similar level of knowledge is often lacking. Compartmentation of cellular metabolism in eukaryotic systems also presents significant challenges for quantitative (13)C-metabolic flux analysis ((13)C-MFA). Recently, innovative (13)C-MFA approaches have been developed based on parallel labeling experiments, the use of multiple isotopic tracers and integrated data analysis, that allow more rigorous validation of pathway models and improved quantification of metabolic fluxes. Applications of these approaches open new research directions in metabolic engineering, biotechnology and medicine.

  6. Samaa : A Software For Air Pollution Modelling and Analysis Activities

    NASA Astrophysics Data System (ADS)

    Gueguen, C.; Mangin, A.; Sanchez, O.

    In order to better understand the qualitative and quantitative evolution of air pollu- tion in cities and their surroundings, ACRI-st has designed and developed, jointly with two French air surveillance networks, an integrated application for air pollution modelling. This simulator, called Samaa, enables testing the impact on pollution of different emission scenarios under a number of meteorological conditions. Samaa is a platform with a user-friendly interface for scenario management, including an emission module, and a GIS-based results viewing module, that may in turn be interfaced with a meteorological and a chemistry/dispersion module (or a dispersion module). The meteorological module is processed first, before any other air pollution module of the simulator. It supplies the meteorological files that will then be used by the emis- sion module and subsequently by the dispersion and chemical modules. This module calculates wind and temperature fields, as well as different meteorological parameters. The AIREMIS emission module was designed to calculate the hourly emissions of seven primary pollutants for each emission sector (transport, industry, heating and natural environment). The GIS, integrated in the emission module, executes two main tasks : - preparation of the emission data sets that the modelling system will process - results viewing for all the different calculation modules (emission, wind and concen- tration maps). The chemistry/dispersion and the dispersion modules enable reactive and non reac- tive pollutants simulation in urban and sub-urban areas. They are interfaced with the other system element to allow simulation of pollutants concentration derived from non chemical or photochemical reactions. Samaa has been validated on two 3-day simulations : the first one was dedicated to evaluate the "chemical processing" of the simulator, and the second one to the "dis- persion processing". The results have proven the strength and the robustness of the

  7. An analysis of interfacial waves and air ingestion mechanisms

    NASA Astrophysics Data System (ADS)

    Galimov, Azat

    This research was focused on developing analytical methods with which to derive the functional forms of the various interfacial forces in two-fluid models [Galimov et al., 2004], and on the Direct Numerical Simulations (DNS) of traveling breaking waves and plunging liquid jets. Analytical results are presented for a stable stratified wavy two-phase flow and the associated interfacial force densities of a two-fluid model. In particular, the non-drag interfacial force density [Drew & Passman, 1998], the Reynolds stress tensor, and the term ( p˜cli -pcl)∇alphacl, which drives surface waves, were derived, where p˜cli is interfacial average pressure, pcl is the average pressure, and alphacl is the volume fraction of the continuous liquid phase. These functional forms are potentially useful for developing two-fluid model closure relations for computational multiphase fluid dynamics (CMFD) numerical solvers. Moreover, it appears that this approach can be generalized to other flow regimes (e.g., annular flows). A comparison of the analytical and ensemble-averaged DNS results show good agreement, and it appears that this approach can be used to develop phenomenological flow-regime-specific closure laws for two-fluid models [Lahey & Drew, 2004], [Lahey, 2005]. A successful 2-D DNS of breaking traveling waves was performed. These calculations had periodic boundary conditions and the physical parameters for air/water flow at atmospheric pressure, including a liquid/gas density ratio of 1,000 and representative surface tension and viscosities. Detailed 3-D DNS was also made for a plunging liquid jet. The processes of forming the liquid jet, the associated air cavity, capturing an initial large donut-shaped air bubble, and developing and breaking-up this bubble into smaller bubbles due to liquid shear, were shown. These simulations showed that the inertia of the liquid jet initially depressed the pool's surface and the toroidal liquid eddy formed subsequently resulted in air

  8. The Third Air Force/NASA Symposium on Recent Advances in Multidisciplinary Analysis and Optimization

    NASA Technical Reports Server (NTRS)

    1990-01-01

    The third Air Force/NASA Symposium on Recent Advances in Multidisciplinary Analysis and Optimization was held on 24-26 Sept. 1990. Sessions were on the following topics: dynamics and controls; multilevel optimization; sensitivity analysis; aerodynamic design software systems; optimization theory; analysis and design; shape optimization; vehicle components; structural optimization; aeroelasticity; artificial intelligence; multidisciplinary optimization; and composites.

  9. MicroRNA regulatory pathway analysis identifies miR-142-5p as a negative regulator of TGF-β pathway via targeting SMAD3

    PubMed Central

    Huang, Wei; Liu, Hui; Zhang, Hong-Mei; Li, Qiubai; Chen, Zhichao; Guo, An-Yuan

    2016-01-01

    MicroRNAs (miRNAs) are non-coding RNAs with functions of posttranscriptional regulation. The abnormally expressed miRNAs have been shown to be crucial contributors and may serve as biomarkers in many diseases. However, determining the biological function of miRNAs is an ongoing challenge. By combining miRNA targets prediction, miRNA and mRNA expression profiles in TCGA cancers, and pathway data, we performed a miRNA-pathway regulation inference by Fisher's exact test for enrichment analysis. Then we constructed a database to show the cancer related miRNA-pathway regulatory network (http://bioinfo.life.hust.edu.cn/miR_path). As one of the miRNAs targeting many cancer related pathways, miR-142-5p potentially regulates the maximum number of genes in TGF-β signaling pathway. We experimentally confirmed that miR-142-5p directly targeted and suppressed SMAD3, a key component in TGF-β signaling. Ectopic overexpression of miR-142-5p significantly promoted tumor cell proliferation and inhibited apoptosis, while silencing of miR-142-5p inhibited the tumor cell proliferation and promoted apoptosis in vitro. These findings indicate that miR-142-5p plays as a negative regulator in TGF-β pathway by targeting SMAD3 and suppresses TGF-β-induced growth inhibition in cancer cells. Our study proved the feasibility of miRNA regulatory pathway analysis and shed light on combining bioinformatics with experiments in the research of complex diseases. PMID:27683030

  10. Novel pathway analysis of genomic polymorphism-cancer risk interaction in the Breast Cancer Prevention Trial

    PubMed Central

    Dunn, Barbara K; Greene, Mark H; Kelley, Jenny M; Costantino, Joseph P; Clifford, Robert J; Hu, Ying; Tang, Gong; Kazerouni, Neely; Rosenberg, Philip S; Meerzaman, Daoud M; Buetow, Kenneth H

    2010-01-01

    Purpose: Tamoxifen was approved for breast cancer risk reduction in high-risk women based on the National Surgical Adjuvant Breast and Bowel Project's Breast Cancer Prevention Trial (P-1:BCPT), which showed 50% fewer breast cancers with tamoxifen versus placebo, supporting tamoxifen's efficacy in preventing breast cancer. Poor metabolizing CYP2D6 variants are currently the subject of intensive scrutiny regarding their impact on clinical outcomes in the adjuvant setting. Our study extends to variants in a wider spectrum of tamoxifen-metabolizing genes and applies to the prevention setting. Methods: Our case-only study, nested within P-1:BCPT, explored associations of polymorphisms in estrogen/tamoxifen-metabolizing genes with responsiveness to preventive tamoxifen. Thirty-nine candidate polymorphisms in 17 candidate genes were genotyped in 249 P-1:BCPT cases. Results: CVP2D6_C1111T, individually and within a CYP2D6 haplotype, showed borderline significant association with treatment arm. Path analysis of the entire tamoxifen pathway gene network showed that the tamoxifen pathway model was consistent with the pattern of observed genotype variability within the placebo-arm dataset. However, correlation of variations in genes in the tamoxifen arm differed significantly from the predictions of the tamoxifen pathway model. Strong correlations between allelic variation in the tamoxifen pathway at CYP1A1-CYP3A4, CYP3A4-CYP2C9, and CYP2C9-SULT1A2, in addition to CYP2D6 and its adjacent genes, were seen in the placebo-arm but not the tamoxifen-arm. In conclusion, beyond reinforcing a role for CYP2D6 in tamoxifen response, our pathway analysis strongly suggests that specific combinations of allelic variants in other genes make major contributions to the tamoxifen-resistance phenotype. PMID:21152245

  11. Identification of genes and signaling pathways associated with diabetic neuropathy using a weighted correlation network analysis

    PubMed Central

    Li, Ya; Ma, Weiguo; Xie, Chuanqing; Zhang, Min; Yin, Xiaohong; Wang, Fenfen; Xu, Jie; Shi, Bingyin

    2016-01-01

    Abstract Background: The molecular mechanisms behind diabetic neuropathy remains to be investigated. Methods: This is a secondary study on microarray dataset (GSE24290) downloaded from Gene Expression Omnibus (GEO) at the National Center for Biotechnology Information (NCBI), which included 18 nerve tissue samples of progressing diabetic neuropathy (fibers loss ≥500 fibers/mm2) and 17 nerve tissue samples of nonprogressing diabetic neuropathy (fibers loss ≤100 fibers/mm2). Differentially expressed genes (DEGs) were screened between progressing and nonprogressing diabetic neuropathy. With the DEGs obtained, a weighted gene coexpression network analysis was conducted to identify gene clusters associated with diabetic neuropathy. Diabetes-related microRNAs (miRNAs) and their target genes were predicted and mapped to the genes in the gene clusters identified. Consequently, a miRNA–gene network was constructed, for which gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis was performed. Potential drugs for treatment of diabetic neuropathy were also predicted. Results: Total 370 upregulated and 379 downregulated DEGs were screened between nonprogressing and progressing diabetic neuropathy. Has-miR-377, has-miR-216a, and has-miR-217 were associated with diabetes. Inflammation was the most significant GO term. The peroxisome proliferator-activated receptor (PPAR) pathway and the adenosine monophosphate (AMP)-activated protein kinase (AMPK) signaling pathway were significantly KEGG pathways significantly enriched with PPAR gamma (PPARG), stearoyl-CoA desaturase (SCD), cluster of differentiation 36 (CD36), and phosphoenolpyruvate carboxykinase 1 (PCK1). Conclusion: The study suggests that PPARG, SCD, CD36, PCK1, AMPK pathway, and PPAR pathway may be involved in progression of diabetic neuropathy. PMID:27893688

  12. Biomass production chamber air analysis of wheat study (BWT931)

    NASA Technical Reports Server (NTRS)

    Batten, J. H.; Peterson, B. V.; Berdis, E.; Wheeler, E. M.

    1993-01-01

    NASA's Controlled Ecological Life Support System (CELSS) biomass production chamber at John F. Kennedy Space Center provides a test bed for bioregenerative studies using plants to provide food, oxygen, carbon dioxide removal, and potable water to humans during long term space travel. Growing plants in enclosed environments has brought about concerns regarding the level of volatile organic compounds (VOC's) emitted from plants and the construction materials that make up the plant growth chambers. In such closed systems, the potential exists for some VOC's to reach toxic levels and lead to poor plant growth, plant death, or health problems for human inhabitants. This study characterized the air in an enclosed environment in which wheat cv. Yocora Rojo was grown. Ninty-four whole air samples were analyzed by gas chromatography/mass spectrometry throughout the eighty-four day planting. VOC emissions from plants and materials were characterized and quantified.

  13. Analysis of Environmentally Friendly Refrigerant Options for Window Air Conditioners

    SciTech Connect

    Bansal, Pradeep; Shen, Bo

    2015-03-12

    This paper presents a technical assessment of environmentally friendly refrigerants as alternatives to R410A for window air conditioners. The alternative refrigerants that are studied for its replacement include R32, a mixture of R32/R125 with 90%/10% molar concentration, R600a, R290, R1234yf, R1234ze and R134a. Baseline experiments were performed on a window unit charged with R410A. The heat pump design model (HPDM) was modified and calibrated with the baseline data and was used to evaluate the comparative performance of the WAC with alternative refrigerants. The paper discusses the advantages and disadvantages of each refrigerants and their suitability for window air conditioners. Among all the refrigerants studied, R32 offers the best efficiency and the lowest Global Warming Potential (GWP), and hence its use will result in the overall environmental friendliness.

  14. Analysis of Environmentally Friendly Refrigerant Options for Window Air Conditioners

    DOE PAGES

    Bansal, Pradeep; Shen, Bo

    2015-03-12

    This paper presents a technical assessment of environmentally friendly refrigerants as alternatives to R410A for window air conditioners. The alternative refrigerants that are studied for its replacement include R32, a mixture of R32/R125 with 90%/10% molar concentration, R600a, R290, R1234yf, R1234ze and R134a. Baseline experiments were performed on a window unit charged with R410A. The heat pump design model (HPDM) was modified and calibrated with the baseline data and was used to evaluate the comparative performance of the WAC with alternative refrigerants. The paper discusses the advantages and disadvantages of each refrigerants and their suitability for window air conditioners. Amongmore » all the refrigerants studied, R32 offers the best efficiency and the lowest Global Warming Potential (GWP), and hence its use will result in the overall environmental friendliness.« less

  15. Deaf Smith County air quality analysis: Letter report: Revision 2

    SciTech Connect

    Not Available

    1985-11-01

    Air quality impacts due to site characterization, and repository construction and operation activities were evaluated in the Deaf Smith County Site, Texas environmental assessment (EA). The analyses on which the impact assessments are based made with dispersion models recommended by the EPA for such applications, meteorological data from a nearby representative National Weather Service station at Amarillo, Texas, and available background air quality data from an urban monitoring location. Maximum offsite concentrations of total suspended particulates, nitrogen dioxide, sulfur dioxide, and carbon monoxide were estimated for periods of maximum emissions identified for each pollutant. Estimates of total annual salt deposition resulting from repository salt handling operations were also made. 36 refs., 5 figs., 17 tabs.

  16. Pollution Emission Analysis of Selected Air Force Aircraft

    DTIC Science & Technology

    1974-04-29

    percent for large non-combat tranaport engines) are proposed. Eraoke numbers wlilch will ensure Invisible aircraft smoke plumes are specified. The...standards are being violated, as well as being significant sources of smoke , ,••(3) that maintenance of the national ambient sir quality BlSndards...and reduced impact of smoke emission requires that air- craft and aircraft engines be Bubjected to a program of control compatible with their

  17. Promoting Geothermal Energy: Air Emissions Comparison and Externality Analysis

    SciTech Connect

    Kagel, Alyssa; Gawell, Karl

    2005-09-01

    When compared to fossil fuel energy sources such as coal and natural gas, geothermal emerges as one of the least polluting forms of energy, producing virtually zero air emissions. Geothermal offers a baseload source of reliable power that compares favorably with fossil fuel power sources. But unless legislative changes are enacted, geothermal energy will continue to be produced at only a fraction of its potential.

  18. Development and Analysis of Desiccant Enhanced Evaporative Air Conditioner Prototype

    SciTech Connect

    Kozubal, E.; Woods, J.; Judkoff, R.

    2012-04-01

    This report documents the design of a desiccant enhanced evaporative air conditioner (DEVAP AC) prototype and the testing to prove its performance. Previous numerical modeling and building energy simulations indicate a DEVAP AC can save significant energy compared to a conventional vapor compression AC (Kozubal et al. 2011). The purposes of this research were to build DEVAP prototypes, test them to validate the numerical model, and identify potential commercialization barriers.

  19. Multilevel analysis of air pollution and early childhood neurobehavioral development.

    PubMed

    Lin, Ching-Chun; Yang, Shih-Kuan; Lin, Kuan-Chia; Ho, Wen-Chao; Hsieh, Wu-Shiun; Shu, Bih-Ching; Chen, Pau-Chung

    2014-07-02

    To investigate the association between the ambient air pollution levels during the prenatal and postnatal stages and early childhood neurobehavioral development, our study recruited 533 mother-infant pairs from 11 towns in Taiwan. All study subjects were asked to complete childhood neurobehavioral development scales and questionnaires at 6 and 18 months. Air pollution, including particulate matter ≤10 μm (PM10), carbon monoxide (CO), sulfur dioxide (SO2), nitrogen dioxide (NO2), ozone (O3), and hydrocarbons, was measured at air quality monitoring stations in the towns where the subjects lived. Multilevel analyses were applied to assess the association between air pollution and childhood neurobehavioral development during pregnancy and when the children were 0 to 6 months, 7 to 12 months, and 13 to 18 months old. At 18 months, poor subclinical neurodevelopment in early childhood is associated with the average SO2 exposure of prenatal, during all trimesters of pregnancy and at postnatal ages up to 12 months (first trimester β = -0.083, se = 0.030; second and third trimester β = -0.114, se = 0.045; from birth to 12 months of age β = -0.091, se = 0.034). Furthermore, adverse gross motor below average scores at six months of age were associated with increased average non-methane hydrocarbon, (NMHC) levels during the second and third trimesters (β = -8.742, se = 3.512). Low-level SO2 exposure prenatally and up to twelve months postnatal could cause adverse neurobehavioral effects at 18 months of age. Maternal NMHC exposure during the 2nd and 3rd trimesters of pregnancy would be also associated with poor gross motor development in their children at 6 months of age.

  20. Multilevel Analysis of Air Pollution and Early Childhood Neurobehavioral Development

    PubMed Central

    Lin, Ching-Chun; Yang, Shih-Kuan; Lin, Kuan-Chia; Ho, Wen-Chao; Hsieh, Wu-Shiun; Shu, Bih-Ching; Chen, Pau-Chung

    2014-01-01

    To investigate the association between the ambient air pollution levels during the prenatal and postnatal stages and early childhood neurobehavioral development, our study recruited 533 mother-infant pairs from 11 towns in Taiwan. All study subjects were asked to complete childhood neurobehavioral development scales and questionnaires at 6 and 18 months. Air pollution, including particulate matter ≤10 μm (PM10), carbon monoxide (CO), sulfur dioxide (SO2), nitrogen dioxide (NO2), ozone (O3), and hydrocarbons, was measured at air quality monitoring stations in the towns where the subjects lived. Multilevel analyses were applied to assess the association between air pollution and childhood neurobehavioral development during pregnancy and when the children were 0 to 6 months, 7 to 12 months, and 13 to 18 months old. At 18 months, poor subclinical neurodevelopment in early childhood is associated with the average SO2 exposure of prenatal, during all trimesters of pregnancy and at postnatal ages up to 12 months (first trimester β = −0.083, se = 0.030; second and third trimester β = −0.114, se = 0.045; from birth to 12 months of age β = −0.091, se = 0.034). Furthermore, adverse gross motor below average scores at six months of age were associated with increased average non-methane hydrocarbon, (NMHC) levels during the second and third trimesters (β = −8.742, se = 3.512). Low-level SO2 exposure prenatally and up to twelve months postnatal could cause adverse neurobehavioral effects at 18 months of age. Maternal NMHC exposure during the 2nd and 3rd trimesters of pregnancy would be also associated with poor gross motor development in their children at 6 months of age. PMID:24992486

  1. Multi-pathway cellular analysis on crude natural drugs/herbs from Japanese Kampo formulations.

    PubMed

    Eshima, Shizuka; Yokoyama, Satoru; Abe, Takashi; Hayakawa, Yoshihiro; Saiki, Ikuo

    2015-01-01

    Kampo formulations comprise a number of crude natural drugs/herbs as constituents. The crude drugs/herbs have been traditionally classified by their traditional classifications or efficacies in Kampo medicines; however, it has been difficult to establish the scientific link between experimental evidence and traditional classifications in Kampo medicine. To clarify such traditional conceptions, we tested 112 crude drugs/herbs that are major components of Kampo formulations, in the multi-pathway analysis of 10 well-studied transcriptional activities including CREB, ERSF, HIF-1α, IRFs, MYC, NF-κB, p53, SMAD, SOX2, and TCF/LEF in A549 human lung cancer cells. By clustering the results of multi-pathway analysis with the Spearman rank-correlation coefficient and Ward linkage, three distinct traditional categories were significantly enriched in the major groupings, which are heat-clearing and dampness-drying herbs, acrid and warm exterior-resolving herbs, and acrid and cool exterior-resolving herbs. These results indicate that these crude drugs/herbs have similar effects on intracellular signaling and further imply that the traditional classifications of those enriched crude drugs/herbs can be supported by such experimental evidence. Collectively, our new in vitro multi-pathway analysis may be useful to clarify the mechanism of action of crude drugs/herbs and Kampo formulations.

  2. Metabolic pathway analysis and kinetic studies for production of nattokinase in Bacillus subtilis.

    PubMed

    Unrean, Pornkamol; Nguyen, Nhung H A

    2013-01-01

    We have constructed a reaction network model of Bacillus subtilis. The model was analyzed using a pathway analysis tool called elementary mode analysis (EMA). The analysis tool was used to study the network capabilities and the possible effects of altered culturing conditions on the production of a fibrinolytic enzyme, nattokinase (NK) by B. subtilis. Based on all existing metabolic pathways, the maximum theoretical yield for NK synthesis in B. subtilis under different substrates and oxygen availability was predicted and the optimal culturing condition for NK production was identified. To confirm model predictions, experiments were conducted by testing these culture conditions for their influence on NK activity. The optimal culturing conditions were then applied to batch fermentation, resulting in high NK activity. The EMA approach was also applied for engineering B. subtilis metabolism towards the most efficient pathway for NK synthesis by identifying target genes for deletion and overexpression that enable the cell to produce NK at the maximum theoretical yield. The consistency between experiments and model predictions proves the feasibility of EMA being used to rationally design culture conditions and genetic manipulations for the efficient production of desired products.

  3. Deriving pathway maps from automated text analysis using a grammar-based approach.

    PubMed

    Olsson, Björn; Gawronska, Barbara; Erlendsson, Björn

    2006-04-01

    We demonstrate how automated text analysis can be used to support the large-scale analysis of metabolic and regulatory pathways by deriving pathway maps from textual descriptions found in the scientific literature. The main assumption is that correct syntactic analysis combined with domain-specific heuristics provides a good basis for relation extraction. Our method uses an algorithm that searches through the syntactic trees produced by a parser based on a Referent Grammar formalism, identifies relations mentioned in the sentence, and classifies them with respect to their semantic class and epistemic status (facts, counterfactuals, hypotheses). The semantic categories used in the classification are based on the relation set used in KEGG (Kyoto Encyclopedia of Genes and Genomes), so that pathway maps using KEGG notation can be automatically generated. We present the current version of the relation extraction algorithm and an evaluation based on a corpus of abstracts obtained from PubMed. The results indicate that the method is able to combine a reasonable coverage with high accuracy. We found that 61% of all sentences were parsed, and 97% of the parse trees were judged to be correct. The extraction algorithm was tested on a sample of 300 parse trees and was found to produce correct extractions in 90.5% of the cases.

  4. Numerical Analysis of Thermal Comfort at Open Air Spaces

    NASA Astrophysics Data System (ADS)

    Papakonstantinou, K.; Belias, C.; Pantos-Kikkos, S.; Assana, A.

    2008-09-01

    The present paper refers to the numerical simulation of air velocity at open air spaces and the conducting thermal comfort after the evaluation of the examined space using CFD methods, taking into account bioclimatic principles at the architectural design. More specially, the paper draws attention to the physical procedures governing air movement at an open environment area in Athens (urban park), named "Attiko Alsos," trying to form them in such way that will lead to the thermal comfort of the area's visitors. The study presents a mathematical model, implemented in a general computer code that can provide detailed information on velocity, prevailing in three-dimensional spaces of any geometrical complexity. Turbulent flow is simulated and buoyancy effects are taken into account. This modelling procedure is intended to contribute to the effort towards designing open areas, such as parks, squares or outdoor building environments, using thermal comfort criteria at the bioclimatic design. A computer model of this kind will provide the architects or the environmental engineers with powerful and economical means of evaluating alternative spaces' designs.

  5. Transcriptome analysis identifies pathways associated with enhanced maternal performance in QSi5 mice

    PubMed Central

    Ramanathan, Palaniappan; Martin, Ian C; Gardiner-Garden, Margaret; Thomson, Peter C; Taylor, Rosanne M; Ormandy, Christopher J; Moran, Christopher; Williamson, Peter

    2008-01-01

    Background Highly fecund mouse strains provide an ideal model to understand the factors affecting maternal performance. The QSi5 inbred strain of mice was selected for high fecundity and low inter-litter interval, and is very successful at weaning large numbers of offspring when compared to other inbred strains. Results Post-natal pup weight gain was used to estimate mammary gland output and to compare the performance of QSi5 mice to CBA mice. Cumulative litter weights and individual pup weight gain was significantly higher throughout the first eight days of lactation in QSi5 mice compared to CBA mice. Morphometric analysis of mammary glands during pregnancy in QSi5 mice revealed a 150 percent greater ductal side branching compared to CBA mice (P < 0.001). Ontology and pathway classification of transcript profiles from the two strains identified an enrichment of genes involved in a number of pathways, including the MAPK, tight junction, insulin signalling and Wnt signalling. Eleven of these genes, including six genes from the MAPK signalling pathway, were identified as associated with postnatal growth. Further, positive mediators of Wnt signalling, including Wnt4, Csnk2a1 and Smad4, were over-represented in the QSi5 strain profile, while negative regulators, including Dkkl1, Ppp2r1a and Nlk, were under-represented. These findings are consistent with the role of Wnt and MAPK signalling pathway in ductal morphogenesis and lobuloalveolar development suggesting enhanced activity in QSi5 mice. A similar pattern of phenotype concordance was seen amongst 12 genes from the tight junction pathway, but a pattern did not emerge from the insulin signalling genes. Amongst a group of differentially expressed imprinted genes, two maternal imprinted genes that suppress growth induced via the IGF signalling pathway, Grb10 and Igf2r, were under-represented in QSi5 mice. Whereas Peg3 and Plagl1, both paternally imprinted genes that enhance neonatal growth, were over-represented in

  6. A Simple Geotracer Compositional Correlation Analysis Reveals Oil Charge and Migration Pathways

    PubMed Central

    Yang, Yunlai; Arouri, Khaled

    2016-01-01

    A novel approach, based on geotracer compositional correlation analysis is reported, which reveals the oil charge sequence and migration pathways for five oil fields in Saudi Arabia. The geotracers utilised are carbazoles, a family of neutral pyrrolic nitrogen compounds known to occur naturally in crude oils. The approach is based on the concept that closely related fields, with respect to filling sequence, will show a higher carbazole compositional correlation, than those fields that are less related. That is, carbazole compositional correlation coefficients can quantify the charge and filling relationships among different fields. Consequently, oil migration pathways can be defined based on the established filling relationships. The compositional correlation coefficients of isomers of C1 and C2 carbazoles, and benzo[a]carbazole for all different combination pairs of the five fields were found to vary extremely widely (0.28 to 0.94). A wide range of compositional correlation coefficients allows adequate differentiation of separate filling relationships. Based on the established filling relationships, three distinct migration pathways were inferred, with each apparently being charged from a different part of a common source kitchen. The recognition of these charge and migration pathways will greatly aid the search for new accumulations. PMID:26965479

  7. Pathway analysis for RNA-Seq data using a score-based approach

    PubMed Central

    Zhou, Yi-Hui

    2016-01-01

    Summary A variety of pathway/gene-set approaches have been proposed to provide evidence of higher-level biological phenomena in the association of expression with experimental condition or clinical outcome. Among these approaches, it has been repeatedly shown that resampling methods are far preferable to approaches that implicitly assume independence of genes. However, few approaches have been optimized for the specific characteristics of RNA-Seq transcription data, in which mapped tags produce discrete counts with varying library sizes, and with potential outliers or skewness patterns that violate parametric assumptions. We describe transformations to RNA-Seq data to improve power for linear associations with outcome and flexibly handle normalization factors. Using these transformations or alternate transformations, we apply recently developed null approximations to quadratic form statistics for both self-contained and competitive pathway testing. The approach provides a convenient integrated platform for RNA-Seq pathway testing. We demonstrate that the approach provides appropriate type I error control without actual permutation and is powerful under many settings in comparison to competing approaches. Pathway analysis of data from a study of F344 vs. HIV1Tg rats, and of sex differences in lymphoblastoid cell lines from humans, strongly supports the biological interpretability of the findings. PMID:26259845

  8. Exploring timing activation of functional pathway based on differential co-expression analysis in preimplantation embryogenesis

    PubMed Central

    Wang, Shanshan; Yang, Lei; Liao, Mingzhi; Wei, Zhuying; Bai, Chunling; Li, Guangpeng

    2016-01-01

    Recent genome-wide omics studies have confirmed the early embryogenesis strictly dependent on the rigorous spatiotemporal activation and multilevel regulation. However, the full effect of functional pathway was not considered. To obtain complete understanding of the gene activation during early development, we performed systematic comparisons based on differential co-expression analysis for bovine preimplantation embryo development (PED). The results confirmed that the functional pathways actively transcribes as early as the 2-cell and 4-cell waves, which Basal transcription factor, Endocytosis and Spliceosome pathway can represent first signs of embryonic activity. Endocytosis act as one of master activators for uncovering a series of successive waves of maternal pioneer signal regulator with the help of Spliceosome complex. Furthermore, the results showed that pattern recognition receptors began to perform its essential function at 4-cell stage, which might be needed to coordinate the later major activation. And finally, our work presented a probable dynamic landscape of key functional pathways for embryogenesis. A clearer understanding of early embryo development will be helpful for Assisted Reproductive Technology (ART) and Regenerative Medicine (RM). PMID:27705919

  9. A Simple Geotracer Compositional Correlation Analysis Reveals Oil Charge and Migration Pathways

    NASA Astrophysics Data System (ADS)

    Yang, Yunlai; Arouri, Khaled

    2016-03-01

    A novel approach, based on geotracer compositional correlation analysis is reported, which reveals the oil charge sequence and migration pathways for five oil fields in Saudi Arabia. The geotracers utilised are carbazoles, a family of neutral pyrrolic nitrogen compounds known to occur naturally in crude oils. The approach is based on the concept that closely related fields, with respect to filling sequence, will show a higher carbazole compositional correlation, than those fields that are less related. That is, carbazole compositional correlation coefficients can quantify the charge and filling relationships among different fields. Consequently, oil migration pathways can be defined based on the established filling relationships. The compositional correlation coefficients of isomers of C1 and C2 carbazoles, and benzo[a]carbazole for all different combination pairs of the five fields were found to vary extremely widely (0.28 to 0.94). A wide range of compositional correlation coefficients allows adequate differentiation of separate filling relationships. Based on the established filling relationships, three distinct migration pathways were inferred, with each apparently being charged from a different part of a common source kitchen. The recognition of these charge and migration pathways will greatly aid the search for new accumulations.

  10. GeneAnalytics Pathway Analysis and Genetic Overlap among Autism Spectrum Disorder, Bipolar Disorder and Schizophrenia

    PubMed Central

    Khanzada, Naveen S.; Butler, Merlin G.; Manzardo, Ann M.

    2017-01-01

    Bipolar disorder (BPD) and schizophrenia (SCH) show similar neuropsychiatric behavioral disturbances, including impaired social interaction and communication, seen in autism spectrum disorder (ASD) with multiple overlapping genetic and environmental influences implicated in risk and course of illness. GeneAnalytics software was used for pathway analysis and genetic profiling to characterize common susceptibility genes obtained from published lists for ASD (792 genes), BPD (290 genes) and SCH (560 genes). Rank scores were derived from the number and nature of overlapping genes, gene-disease association, tissue specificity and gene functions subdivided into categories (e.g., diseases, tissues or functional pathways). Twenty-three genes were common to all three disorders and mapped to nine biological Superpathways including Circadian entrainment (10 genes, score = 37.0), Amphetamine addiction (five genes, score = 24.2), and Sudden infant death syndrome (six genes, score = 24.1). Brain tissues included the medulla oblongata (11 genes, score = 2.1), thalamus (10 genes, score = 2.0) and hypothalamus (nine genes, score = 2.0) with six common genes (BDNF, DRD2, CHRNA7, HTR2A, SLC6A3, and TPH2). Overlapping genes impacted dopamine and serotonin homeostasis and signal transduction pathways, impacting mood, behavior and physical activity level. Converging effects on pathways governing circadian rhythms support a core etiological relationship between neuropsychiatric illnesses and sleep disruption with hypoxia and central brain stem dysfunction. PMID:28264500

  11. A regularized Hotelling’s T2 test for pathway analysis in proteomic studies

    PubMed Central

    Chen, Lin S.; Paul, Debashis; Prentice, Ross L.; Wang, Pei

    2013-01-01

    Recent proteomic studies have identified proteins related to specific phenotypes. In addition to marginal association analysis for individual proteins, analyzing pathways (functionally related sets of proteins) may yield additional valuable insights. Identifying pathways that differ between phenotypes can be conceptualized as a multivariate hypothesis testing problem: whether the mean vector μ of a p-dimensional random vector X is μ0. Proteins within the same biological pathway may correlate with one another in a complicated way, and type I error rates can be inflated if such correlations are incorrectly assumed to be absent. The inflation tends to be more pronounced when the sample size is very small or there is a large amount of missingness in the data, as is frequently the case in proteomic discovery studies. To tackle these challenges, we propose a regularized Hotelling’s T2 (RHT) statistic together with a non-parametric testing procedure, which effectively controls the type I error rate and maintains good power in the presence of complex correlation structures and missing data patterns. We investigate asymptotic properties of the RHT statistic under pertinent assumptions and compare the test performance with four existing methods through simulation examples. We apply the RHT test to a hormone therapy proteomics data set, and identify several interesting biological pathways for which blood serum concentrations changed following hormone therapy initiation. PMID:23997374

  12. FMM: a web server for metabolic pathway reconstruction and comparative analysis.

    PubMed

    Chou, Chih-Hung; Chang, Wen-Chi; Chiu, Chih-Min; Huang, Chih-Chang; Huang, Hsien-Da

    2009-07-01

    Synthetic Biology, a multidisciplinary field, is growing rapidly. Improving the understanding of biological systems through mimicry and producing bio-orthogonal systems with new functions are two complementary pursuits in this field. A web server called FMM (From Metabolite to Metabolite) was developed for this purpose. FMM can reconstruct metabolic pathways form one metabolite to another metabolite among different species, based mainly on the Kyoto Encyclopedia of Genes and Genomes (KEGG) database and other integrated biological databases. Novel presentation for connecting different KEGG maps is newly provided. Both local and global graphical views of the metabolic pathways are designed. FMM has many applications in Synthetic Biology and Metabolic Engineering. For example, the reconstruction of metabolic pathways to produce valuable metabolites or secondary metabolites in bacteria or yeast is a promising strategy for drug production. FMM provides a highly effective way to elucidate the genes from which species should be cloned into those microorganisms based on FMM pathway comparative analysis. Consequently, FMM is an effective tool for applications in synthetic biology to produce both drugs and biofuels. This novel and innovative resource is now freely available at http://FMM.mbc.nctu.edu.tw/.

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

    PubMed

    Ataman, Meric; Hatzimanikatis, Vassily

    2015-12-01

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

  14. Investigation into the importance of the stomatal pathway in the exchange of PCBs between air and plants.

    PubMed

    Barber, Jonathan L; Kurt, Perihan B; Thomas, Gareth O; Kerstiens, Gerhard; Jones, Kevin C

    2002-10-15

    The transfer of persistent organic pollutants (POPs) from air to vegetation is an important air-surface exchange process that affects global cycling and can result in human and wildlife exposure via the terrestrial food chain. To improve understanding of this process, the role of stomata in uptake of gas-phase polychlorinated biphenyls (PCBs) was investigated using Hemerocallis x hybrida "Black Eyed Stella", a plant with a high stomatal density. Uptake of PCBs was monitored over a 72-h period in the presence and absence of light. Uptake rates were significantly greater in illuminated (stomata open) plants than unilluminated (stomata closed) plants for 18 of the 28 measured PCB congeners (p < 0.05). Depuration of PCBs was monitored in a subsequent experiment over a period of 3 weeks. Levels after 3 weeks of depuration time were still much higher than the concentration prior to contamination. Tri- and tetrachlorinated PCBs showed the greatest depuration, with less than 20% and 50% of accumulated PCBs respectively remaining, while approximately 70% of higher chlorinated PCB congeners remained in the plants at the end of the experiment. Treatments with/without light (to control stomatal opening during uptake) and with/without abscisic acid (ABA) application (to control stomatal opening during depuration) were compared. After contamination indoors for 3 days, there was a significantly higher concentration of PCBs (p < 0.05) in the light contaminated plants than the dark-contaminated plants for 13 of the 28 measured PCB congeners. The ABA treatment affected depuration of PCB-18 only. "Light/ABA-treated" plants had a significantly slower depuration rate for PCB-18 than "light/untreated", "dark/ABA-treated", and "dark/untreated" plants (p < 0.05). The results of the study indicate that there is a stomatal effect on the rate of exchange of PCBs between Hemerocallis leaves and air.

  15. Uncertainty and sensitivity analysis of food pathway results with the MACCS Reactor Accident Consequence Model

    SciTech Connect

    Helton, J.C.; Johnson, J.D.; Rollstin, J.A.; Shiver, A.W.; Sprung, J.L.

    1995-01-01

    Uncertainty and sensitivity analysis techniques based on Latin hypercube sampling, partial correlation analysis and stepwise regression analysis are used in an investigation with the MACCS model of the food pathways associated with a severe accident at a nuclear power station. The primary purpose of this study is to provide guidance on the variables to be considered in future review work to reduce the uncertainty in the important variables used in the calculation of reactor accident consequences. The effects of 87 imprecisely-known input variables on the following reactor accident consequences are studied: crop growing season dose, crop long-term dose, milk growing season dose, total food pathways dose, total ingestion pathways dose, total long-term pathways dose, area dependent cost, crop disposal cost, milk disposal cost, condemnation area, crop disposal area and milk disposal area. When the predicted variables are considered collectively, the following input variables were found to be the dominant contributors to uncertainty: fraction of cesium deposition on grain fields that is retained on plant surfaces and transferred directly to grain, maximum allowable ground concentrations of Cs-137 and Sr-90 for production of crops, ground concentrations of Cs-134, Cs-137 and I-131 at which the disposal of milk will be initiated due to accidents that occur during the growing season, ground concentrations of Cs-134, I-131 and Sr-90 at which the disposal of crops will be initiated due to accidents that occur during the growing season, rate of depletion of Cs-137 and Sr-90 from the root zone, transfer of Sr-90 from soil to legumes, transfer of Cs-137 from soil to pasture, transfer of cesium from animal feed to meat, and the transfer of cesium, iodine and strontium from animal feed to milk.

  16. Groundwater Pathway Scoping Analysis for Disposal of APT and TEF Wastes

    SciTech Connect

    Cook, J.R.

    1998-09-16

    The methods used to analyze the long-term performance of APT and TEF waste, with respect to the groundwater pathway, disposed in Intermediate Level vaults are described in this report. The purpose of this work is to reduce the number of radionuclides that need to be considered in a detailed analysis of performance. A methodology was selected that is more rigorous than the screening analysis described earlier1, but still conservative enough that radionuclides shown to have minimal dose impact using the methodology can be neglected with assurance that they would not have produced significant results if included in a detailed computer model.

  17. Thermal analysis of HTS air-core transformer used in voltage compensation type active SFCL

    NASA Astrophysics Data System (ADS)

    Song, M.; Tang, Y.; Li, J.; Zhou, Y.; Chen, L.; Ren, L.

    2010-11-01

    The three-phase voltage compensation type active superconducting fault current limiter (SFCL) is composed of three HTS air-core transformers and a three-phase four-wire Pulse Width Modulation (PWM) converter. The primary winding of the each phase HTS air-core transformer is in series with the main system, and the second winding is connected with the PWM converter. The single-phase conduction-cooled HTS air-core transformer is consisting of four double-pancakes wound by the Bi2223/Ag tape. In this paper, according to the electromagnetic analysis on the single-phase HTS air-core transformer, its AC loss corresponding to different operation modes is calculated. Furthermore, the thermal behaviors are studied by the time-stepping numerical simulations. On the basis of the simulation results, the related problems with the HTS air-core transformer's thermal stability are discussed.

  18. Dry Air Cooler Modeling for Supercritical Carbon Dioxide Brayton Cycle Analysis

    SciTech Connect

    Moisseytsev, A.; Sienicki, J. J.; Lv, Q.

    2016-07-28

    Modeling for commercially available and cost effective dry air coolers such as those manufactured by Harsco Industries has been implemented in the Argonne National Laboratory Plant Dynamics Code for system level dynamic analysis of supercritical carbon dioxide (sCO2) Brayton cycles. The modeling can now be utilized to optimize and simulate sCO2 Brayton cycles with dry air cooling whereby heat is rejected directly to the atmospheric heat sink without the need for cooling towers that require makeup water for evaporative losses. It has sometimes been stated that a benefit of the sCO2 Brayton cycle is that it enables dry air cooling implying that the Rankine steam cycle does not. A preliminary and simple examination of a Rankine superheated steam cycle and an air-cooled condenser indicates that dry air cooling can be utilized with both cycles provided that the cycle conditions are selected appropriately

  19. Framework for the uncertainty assessment in the impact pathway analysis with an application on a local scale in Spain.

    PubMed

    Sonnemann, Guido W; Pla, Yolanda; Schuhmacher, Marta; Castells, Francesc

    2002-04-01

    The estimation of damage estimates due to air emissions gives important basic knowledge for decision-making on the level of environmental politics and business strategies. Nowadays, a frequently applied method to estimate environmental damages is the Impact Pathway Analysis (IPA), which can be easily carried out using models such as EcoSense or PathWays. These models produce results in a relatively short term. However, there is a lack of reliability in the results. As in many other environmental software tools, the uncertainty is the key problem that makes it difficult to convince decision-makers by the outcomes of a study. Therefore, a framework that allows assessing the uncertainties within studies in which the IPA is applied on a local scale has been developed. In this assessment framework, the uncertainties of the used parameters, including their spatial and temporal variability, are taken into account. As the model is processing a huge quantity of data, one step of the assessment consists of a screening procedure to determine the parameters that are supposed to be fixed. For the other data, probability distributions have to be selected and classified into two groups: extensively available data for which average and standard deviation can be calculated and data based on little information. A quantification of the uncertainty can be completed by a stochastic model in the form of Monte Carlo (MC) simulation on the basis of the framework. As an illustration of the framework, we have applied it to a study on the installation of an advanced gas treatment in the municipal waste incinerator of Tarragona. It can be shown that the presented stochastic approach gives a lower geometric deviation than the analytical one and that the new gas treatment reduces the environmental damages without any doubt.

  20. Genome-wide association and pathway analysis of feed efficiency in pigs reveal candidate genes and pathways for residual feed intake.

    PubMed

    Do, Duy N; Strathe, Anders B; Ostersen, Tage; Pant, Sameer D; Kadarmideen, Haja N

    2014-01-01

    Residual feed intake (RFI) is a complex trait that is economically important for livestock production; however, the genetic and biological mechanisms regulating RFI are largely unknown in pigs. Therefore, the study aimed to identify single nucleotide polymorphisms (SNPs), candidate genes and biological pathways involved in regulating RFI using Genome-wide association (GWA) and pathway analyses. A total of 596 Yorkshire boars with phenotypes for two different measures of RFI (RFI1 and 2) and 60k genotypic data was used. GWA analysis was performed using a univariate mixed model and 12 and 7 SNPs were found to be significantly associated with RFI1 and RFI2, respectively. Several genes such as xin actin-binding repeat-containing protein 2 (XIRP2),tetratricopeptide repeat domain 29 (TTC29),suppressor of glucose, autophagy associated 1 (SOGA1),MAS1,G-protein-coupled receptor (GPCR) kinase 5 (GRK5),prospero-homeobox protein 1 (PROX1),GPCR 155 (GPR155), and FYVE domain containing the 26 (ZFYVE26) were identified as putative candidates for RFI based on their genomic location in the vicinity of these SNPs. Genes located within 50 kbp of SNPs significantly associated with RFI and RFI2 (q-value ≤ 0.2) were subsequently used for pathway analyses. These analyses were performed by assigning genes to biological pathways and then testing the association of individual pathways with RFI using a Fisher's exact test. Metabolic pathway was significantly associated with both RFIs. Other biological pathways regulating phagosome, tight junctions, olfactory transduction, and insulin secretion were significantly associated with both RFI traits when relaxed threshold for cut-off p-value was used (p ≤ 0.05). These results implied porcine RFI is regulated by multiple biological mechanisms, although the metabolic processes might be the most important. Olfactory transduction pathway controlling the perception of feed via smell, insulin pathway controlling food intake might be important

  1. Analysis of non-CFC automotive air conditioning

    SciTech Connect

    Mei, V.C.; Chen, F.C. ); Sullivan, R.A. )

    1991-01-01

    Concern about the destruction of the global environment by chlorofluorocarbon (CFC) fluids has become an impetus in searching for alternative non-CFC refrigerants and cooling methods for mobile air conditioning (MAC). While some alternative refrigerants have been identified, they are not considered a lasting solution because of their high global warming potential (GWP), which could result in their eventual phase-out. In view of this dilemma, environmentally acceptable alternative cooling methods have become important. This study discusses the advantages and the limits of some of the alternative automotive cooling methodologies. 19 refs., 6 figs.

  2. Association between FOXM1 and hedgehog signaling pathway in human cervical carcinoma by tissue microarray analysis

    PubMed Central

    Chen, Hong; Wang, Jingjing; Yang, Hong; Chen, Dan; Li, Panpan

    2016-01-01

    Forkhead box M1 (FOXM1) and hedgehog (Hh) signaling pathway are implicated in the formation and development of human tumors, including cervical cancer. Previous studies have indicated that FOXM1 may be a downstream target gene of the Hh signaling pathway, but their association in cervical cancer is largely unknown. In the present study, the expression of FOXM1 and Hh signaling molecules was evaluated by immunohistochemical analysis in a tissue microarray that contained 70 cervical cancer tissues and 10 normal cervical tissues. In addition, the association of these molecules with clinicopathological parameters, and the association between FOXM1 and various molecules involved in the Hh signaling pathway was investigated. The results indicated that FOXM1 and Hh signaling molecules were overexpressed in cervical cancer tissues. The protein expression levels of FOXM1, glioma-associated oncogene 1 (GLI1) and smoothened (SMO) correlated with the clinical stage of the tumors, while the protein expression levels of Sonic Hh (SHh), patched 1 (PTCH1) and GLI1 correlated with the pathological grade of the tumors. The expression levels of GLI1 were lower in tissues without lymph node metastasis than in tissues with lymph node metastasis. In addition, FOXM1 expression correlated with GLI1, SHh and PTCH1 expression in cancer tissues. These findings confirmed the participation of FOXM1 and the Hh signaling pathway in cervical cancer. Furthermore, the finding that FOXM1 may be a downstream target gene of the Hh signaling pathway in cervical cancer provides a potential novel diagnostic and therapeutic target for cervical cancer. PMID:27698840

  3. Elementary Flux Mode Analysis of Acetyl-CoA Pathway in Carboxydothermus hydrogenoformans Z-2901

    PubMed Central

    Chinnasamy Perumal, Rajadurai; Selvaraj, Ashok; Ramesh Kumar, Gopal

    2014-01-01

    Carboxydothermus hydrogenoformans is a carboxydotrophic hydrogenogenic bacterium species that produces hydrogen molecule by utilizing carbon monoxide (CO) or pyruvate as a carbon source. To investigate the underlying biochemical mechanism of hydrogen production, an elementary mode analysis of acetyl-CoA pathway was performed to determine the intermediate fluxes by combining linear programming (LP) method available in CellNetAnalyzer software. We hypothesized that addition of enzymes necessary for carbon monoxide fixation and pyruvate dissimilation would enhance the theoretical yield of hydrogen. An in silico gene knockout of pyk, pykC, and mdh genes of modeled acetyl-CoA pathway allows the maximum theoretical hydrogen yield of 47.62 mmol/gCDW/h for 1 mole of carbon monoxide (CO) uptake. The obtained hydrogen yield is comparatively two times greater than the previous experimental data. Therefore, it could be concluded that this elementary flux mode analysis is a crucial way to achieve efficient hydrogen production through acetyl-CoA pathway and act as a model for strain improvement. PMID:24822064

  4. Analysis of the biosynthetic pathway for sulfoquinovosyldiacylglycerol in the purple bacterium R. sphaeroides

    SciTech Connect

    Benning, C.; Somerville, C.R. )

    1990-05-01

    The membrane lipid sulfoquinovosyldiacylglycerol (SQD) can be found in all photosynthetically active membranes studied. In a green leaf, about 50% of the organic sulfur is bound in SQD. Therefore, this sulfolipid constitutes a major component of the global sulfur cycle. However, since the discovery of SQD, very little progress has been made towards the elucidation of the biosynthetic pathway. For a genetical analysis of the pathway of SQD, we selected the photosynthetic purple-nonsulfur bacterium R. sphaeroides, as our model system. We have been able to isolate several classes of mutants, which show reduced levels of SQD. Some of the mutants accumulate {sup 35}S-labeled, water soluble compounds. We expect that these compounds are related to precursors or are precursors, which accumulate due to a specific block in the biosynthetic pathway of SQD. To study the possible precursor function of these compounds, we developed an in vitro SQD biosynthesis system using cell free extracts from R. sphaeroides. In addition, we have been able to isolate cosmids prepared from WT DNA, which complement three classes of SQD mutants in R. sphaeroides. The analysis and expression of the genes encoded by these cosmids should facilitate the characterization of the proteins involved in SQD biosynthesis.

  5. Novel degradation pathway and kinetic analysis for buprofezin removal by newly isolated Bacillus sp.

    PubMed

    Wang, Guangli; Xu, Dayong; Xiong, Minghua; Zhang, Hui; Li, Feng; Liu, Yuan

    2016-09-15

    Given the intensive and widespread application of the pesticide, buprofezin, its environmental residues potentially pose a problem; yet little is known about buprofezin's kinetic and metabolic behaviors. In this study, a novel gram-positive strain, designated BF-5, isolated from aerobic activated sludge, was found to be capable of metabolizing buprofezin as its sole energy, carbon, and nitrogen source. Based on its physiological and biochemical characteristics, other aspects of its phenotype, and a phylogenetic analysis, strain BF-5 was identified as Bacillus sp. This study investigated the effect of culture conditions on bacterial growth and substrate degradation, such as pH, temperature, initial concentration, different nitrogen source, and additional nitrogen sources as co-substrates. The degradation rate parameters, qmax, Ks, Ki and Sm were determined to be 0.6918 h(-1), 105.4 mg L(-1), 210.5 mg L(-1), and 148.95 mg L(-1) respectively. The capture of unpublished potential metabolites by gas chromatography-mass spectrometry (GC-MS) analysis has led to the proposal of a novel degradation pathway. Taken together, our results clarify buprofezin's biodegradation pathway(s) and highlight the promising potential of strain BF-5 in bioremediation of buprofezin-contaminated environments.

  6. Comparative analysis of air pollution emissions by electric utilities: Public policy implications

    NASA Astrophysics Data System (ADS)

    Freedman, Martin; Jaggi, Bikki

    1991-09-01

    One of the objectives of US environmental regulations was to reduce industrial air pollution emissions, especially from the electric utility industry, the major industrial air polluter. In this study, a comparative analysis of air pollution emissions from fossil-fuel-burning electric utility plants is conducted. The analysis focuses on a 12-yr period from 1975 to 1987 for three air pollutants: particulates, surfur dioxide, and nitrogen oxides. The results indicate that particulate emissions have been significantly reduced but that sulfur dioxide and nitrogen oxides are still major problems for a number of plants. Furthermore, the disparity in the performance by plants indicates that by using current technology, the industry as a whole could greatly reduce these emissions. These results have policy implication for future environmental legislation.

  7. Air quality impacts analysis for area G. Final report

    SciTech Connect

    Kowalewsky, K.; Eklund, B.; Vold, E.L.

    1995-07-05

    The impact of fugitive radioactive emissions from the disposal site, Area G, was evaluated in support of site characterization for the Performance Assessment and for the Radioactive Air Emissions Management (RAEM) program. Fugitive emissions of tritiated water and contaminated windblown dust were considered. Data from an extensive field measurement program were used to estimate annual emissions of tritiated water. Fugitive dust models were used to calculate estimates of the annual emissions of windblown dust. These estimates were combined with data on contamination levels in surface soils to develop annual emission rates for specific radionuclides: tritium, uranium-238, cesium-137, plutonium-238, plutonium-239,240, and strontium-90. The CAP-88 atmospheric transport model was used to predict areas potentially affected by long-term dust deposition and atmospheric concentrations. The annual emission rate of tritiated water was estimated from the field data to be 14.0 Ci/yr. The emission rate of soil-borne radionuclides from open areas and from soils handling operations totaled less than 1x10{sup -4} Ci/yr. The CAP-88 results were used to develop effective dose equivalents (EDEs) for receptor locations downwind of Area G. All EDEs were several orders of magnitude below the national standard of 10 mrem/yr. Fugitive air emissions from Area G were found not to pose a health threat to persons living or working downwind of the facility.

  8. Life cycle assessment and nutrient analysis of various processing pathways in algal biofuel production.

    PubMed

    Mu, Dongyan; Ruan, Roger; Addy, Min; Mack, Sarah; Chen, Paul; Zhou, Yong

    2017-04-01

    This study focuses on analyzing nutrient distributions and environmental impacts of nutrient recycling, reusing, and discharging in algal biofuels production. The three biomass conversion pathways compared in this study were: hydrothermal liquefaction technology (HTL), hydrothermal hydrolysis pretreatment +HTL (HTP), and wet lipid extraction (WLE). Carbon, nitrogen, and phosphorous (C, N, P) flows were described in each pathway. A primary cost analysis was conducted to evaluate the economic performance. The LCA results show that the HTP reduced life cycle NOx emissions by 10% from HTL, but increased fossil fuel use, greenhouse gas emissions, and eutrophication potential by 14%, 5%, and 28% respectively. The cost of per gallon biodiesel produced in HTP was less than in HTL. To further reduce emissions, efforts should be focused on improving nutrient uptake rates in algae cultivation, increasing biomass carbon detention in hydrothermal hydrolysis, and/or enhancing biomass conversion rates in the biooil upgrading processes.

  9. Pathway analysis from lists of microRNAs: common pitfalls and alternative strategy.

    PubMed

    Godard, Patrice; van Eyll, Jonathan

    2015-04-20

    MicroRNAs (miRNAs) are involved in the regulation of gene expression at a post-transcriptional level. As such, monitoring miRNA expression has been increasingly used to assess their role in regulatory mechanisms of biological processes. In large scale studies, once miRNAs of interest have been identified, the target genes they regulate are often inferred using algorithms or databases. A pathway analysis is then often performed in order to generate hypotheses about the relevant biological functions controlled by the miRNA signature. Here we show that the method widely used in scientific literature to identify these pathways is biased and leads to inaccurate results. In addition to describing the bias and its origin we present an alternative strategy to identify potential biological functions specifically impacted by a miRNA signature. More generally, our study exemplifies the crucial need of relevant negative controls when developing, and using, bioinformatics methods.

  10. Pathway analysis from lists of microRNAs: common pitfalls and alternative strategy

    PubMed Central

    Godard, Patrice; van Eyll, Jonathan

    2015-01-01

    MicroRNAs (miRNAs) are involved in the regulation of gene expression at a post-transcriptional level. As such, monitoring miRNA expression has been increasingly used to assess their role in regulatory mechanisms of biological processes. In large scale studies, once miRNAs of interest have been identified, the target genes they regulate are often inferred using algorithms or databases. A pathway analysis is then often performed in order to generate hypotheses about the relevant biological functions controlled by the miRNA signature. Here we show that the method widely used in scientific literature to identify these pathways is biased and leads to inaccurate results. In addition to describing the bias and its origin we present an alternative strategy to identify potential biological functions specifically impacted by a miRNA signature. More generally, our study exemplifies the crucial need of relevant negative controls when developing, and using, bioinformatics methods. PMID:25800743

  11. Fuzzy Logic Analysis of Kinase Pathway Crosstalk in TNF/EGF/Insulin-Induced Signaling

    PubMed Central

    Aldridge, Bree B.; Saez-Rodriguez, Julio; Muhlich, Jeremy L.; Sorger, Peter K.; Lauffenburger, Douglas A.

    2009-01-01

    When modeling cell signaling networks, a balance must be struck between mechanistic detail and ease of interpretation. In this paper we apply a fuzzy logic framework to the analysis of a large, systematic dataset describing the dynamics of cell signaling downstream of TNF, EGF, and insulin receptors in human colon carcinoma cells. Simulations based on fuzzy logic recapitulate most features of the data and generate several predictions involving pathway crosstalk and regulation. We uncover a relationship between MK2 and ERK pathways that might account for the previously identified pro-survival influence of MK2. We also find unexpected inhibition of IKK following EGF treatment, possibly due to down-regulation of autocrine signaling. More generally, fuzzy logic models are flexible, able to incorporate qualitative and noisy data, and powerful enough to produce quantitative predictions and new biological insights about the operation of signaling networks. PMID:19343194

  12. An Analysis of Subordinates’ Perceptions of the Effectiveness of Female Supervisors in the Air Force.

    DTIC Science & Technology

    1983-09-28

    7 -I4994 AN ANALYSISS OFOSUBORDINTES’ PERCEPTIONS OF THE 1/2EFFECTIVENESS OF FEMALE S--(U) AIR FORCE INST OF TECHRIGHT-PATTERSON AiFB OH SCHOOL OF...8217 PERCEPTIONS OF THE EFFECTIVENESS OF FEMALE SUPERVISORS IN THE AIR FORCE ’ j Charlotte L. Rea, Captain, USAF LSSR 82-83 DTIC b-C-, AN NALYSS OF UBORDNATES...in/ Ava il ib-itv Ccds Av:,t4I and/ur Dist Special AN ANALYSIS OF SUBORDINATES’ PERCEPTIONS OF THE EFFECTIVENESS OF FEMALE SUPERVISORS IN THE AIR

  13. Aircraft/Air Traffic Management Functional Analysis Model: Technical Description. 2.0

    NASA Technical Reports Server (NTRS)

    Etheridge, Melvin; Plugge, Joana; Retina, Nusrat

    1998-01-01

    The Aircraft/Air Traffic Management Functional Analysis Model, Version 2.0 (FAM 2.0), is a discrete event simulation model designed to support analysis of alternative concepts in air traffic management and control. FAM 2.0 was developed by the Logistics Management Institute (LMI) under a National Aeronautics and Space Administration (NASA) contract. This document provides a technical description of FAM 2.0 and its computer files to enable the modeler and programmer to make enhancements or modifications to the model. Those interested in a guide for using the model in analysis should consult the companion document, Aircraft/Air Traffic Management Functional Analysis Model, Version 2.0 Users Manual.

  14. Analysis of United States Air Forces Central Government Purchase Card Reachback Viability

    DTIC Science & Technology

    2011-12-01

    Analysis of United States Air Forces Central Government Purchase Card Reachback Viability 1 December 2011 by Capt. Jason R. Ackiss, USAF...United States Air Forces Central Government Purchase Card Reachback Viability 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6...USAFCENT) government purchase card (GPC) purchases by utilizing reachback services. The study analyzed FY 2011 data to include the number of

  15. Dynamic Response Analysis of an Icosahedron Shaped Lighter Than Air Vehicle

    DTIC Science & Technology

    2015-03-26

    results using a modal analysis. The experimental setup designed will allow future research on the interaction between the frame and skin of icosahedron...Icosahedron Frame ( on Right) with Membrane Skin ( on Left)......................... 13 Figure 3: Beam Cross-section for Icosahedron Frame ...LTAV Lighter Than Air Vehicle m Meter M Mass Matrix MATLAB Matrix Laboratory MAV Micro Air Vehicle MPa Megapascal n Mode Number N Number of

  16. An approach to market analysis for lighter than air transportation of freight

    NASA Technical Reports Server (NTRS)

    Roberts, P. O.; Marcus, H. S.; Pollock, J. H.

    1975-01-01

    An approach is presented to marketing analysis for lighter than air vehicles in a commercial freight market. After a discussion of key characteristics of supply and demand factors, a three-phase approach to marketing analysis is described. The existing transportation systems are quantitatively defined and possible roles for lighter than air vehicles within this framework are postulated. The marketing analysis views the situation from the perspective of both the shipper and the carrier. A demand for freight service is assumed and the resulting supply characteristics are determined. Then, these supply characteristics are used to establish the demand for competing modes. The process is then iterated to arrive at the market solution.

  17. Pathway-based network analysis of myeloma tumors: monoclonal gammopathy of unknown significance, smoldering multiple myeloma, and multiple myeloma.

    PubMed

    Dong, L; Chen, C Y; Ning, B; Xu, D L; Gao, J H; Wang, L L; Yan, S Y; Cheng, S

    2015-08-14

    Although many studies have been carried out on monoclonal gammopathy of unknown significances (MGUS), smoldering multiple myeloma (SMM), and multiple myeloma (MM), their classification and underlying pathogenesis are far from elucidated. To discover the relationships among MGUS, SMM, and MM at the transcriptome level, differentially expressed genes in MGUS, SMM, and MM were identified by the rank product method, and then co-expression networks were constructed by integrating the data. Finally, a pathway-network was constructed based on Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis, and the relationships between the pathways were identified. The results indicated that there were 55, 78, and 138 pathways involved in the myeloma tumor developmental stages of MGUS, SMM, and MM, respectively. The biological processes identified therein were found to have a close relationship with the immune system. Processes and pathways related to the abnormal activity of DNA and RNA were also present in SMM and MM. Six common pathways were found in the whole process of myeloma tumor development. Nine pathways were shown to participate in the progression of MGUS to SMM, and prostate cancer was the sole pathway that was involved only in MGUS and MM. Pathway-network analysis might provide a new indicator for the developmental stage diagnosis of myeloma tumors.

  18. The mechanisms of nickel toxicity in aquatic environments: an adverse outcome pathway analysis.

    PubMed

    Brix, Kevin V; Schlekat, Christian E; Garman, Emily R

    2016-12-09

    Current ecological risk assessment and water quality regulations for nickel (Ni) use mechanistically based, predictive tools such as biotic ligand models (BLMs). However, despite many detailed studies, the precise mechanism(s) of Ni toxicity to aquatic organisms remains elusive. This uncertainty in the mechanism(s) of action for Ni has led to concern over the use of tools like the BLM in some regulatory settings. To address this knowledge gap, the authors used an adverse outcome pathway (AOP) analysis, the first AOP for a metal, to identify multiple potential mechanisms of Ni toxicity and their interactions with freshwater aquatic organisms. The analysis considered potential mechanisms of action based on data from a wide range of organisms in aquatic and terrestrial environments on the premise that molecular initiating events for an essential metal would potentially be conserved across taxa. Through this analysis the authors identified 5 potential molecular initiating events by which Ni may exert toxicity on aquatic organisms: disruption of Ca(2+) homeostasis, disruption of Mg(2+) homeostasis, disruption of Fe(2+/3+) homeostasis, reactive oxygen species-induced oxidative damage, and an allergic-type response of respiratory epithelia. At the organ level of biological organization, these 5 potential molecular initiating events collapse into 3 potential pathways: reduced Ca(2+) availability to support formation of exoskeleton, shell, and bone for growth; impaired respiration; and cytotoxicity and tumor formation. At the level of the whole organism, the organ-level responses contribute to potential reductions in growth and reproduction and/or alterations in energy metabolism, with several potential feedback loops between each of the pathways. Overall, the present AOP analysis provides a robust framework for future directed studies on the mechanisms of Ni toxicity and for developing AOPs for other metals. Environ Toxicol Chem 2017;9999:1-10. © 2016 SETAC.

  19. Identification of Genes Discriminating Multiple Sclerosis Patients from Controls by Adapting a Pathway Analysis Method

    PubMed Central

    Zhang, Lei; Wang, Linlin; Tian, Pu

    2016-01-01

    The focus of analyzing data from microarray experiments has shifted from the identification of associated individual genes to that of associated biological pathways or gene sets. In bioinformatics, a feature selection algorithm is usually used to cope with the high dimensionality of microarray data. In addition to those algorithms that use the biological information contained within a gene set as a priori to facilitate the process of feature selection, various gene set analysis methods can be applied directly or modified readily for the purpose of feature selection. Significance analysis of microarray to gene-set reduction analysis (SAM-GSR) algorithm, a novel direction of gene set analysis, is one of such methods. Here, we explore the feature selection property of SAM-GSR and provide a modification to better achieve the goal of feature selection. In a multiple sclerosis (MS) microarray data application, both SAM-GSR and our modification of SAM-GSR perform well. Our results show that SAM-GSR can carry out feature selection indeed, and modified SAM-GSR outperforms SAM-GSR. Given pathway information is far from completeness, a statistical method capable of constructing biologically meaningful gene networks is of interest. Consequently, both SAM-GSR algorithms will be continuously revaluated in our future work, and thus better characterized. PMID:27846233

  20. COMPARISON OF FAST GC/TOFMS WITH METHOD TO-14 FOR ANALYSIS OF AMBIENT AIR SAMPLES

    EPA Science Inventory

    Field studies using portable gas chromatographs (PGC) to analyze volatile organic compounds in ambient air usually include, as reference standard method, the analysis of concurrent, collocated canister samples by EPA Method TO-14. Each laboratory analysis takes about an hour a...

  1. Design and analysis of aluminum/air battery system for electric vehicles

    NASA Astrophysics Data System (ADS)

    Yang, Shaohua; Knickle, Harold

    Aluminum (Al)/air batteries have the potential to be used to produce power to operate cars and other vehicles. These batteries might be important on a long-term interim basis as the world passes through the transition from gasoline cars to hydrogen fuel cell cars. The Al/air battery system can generate enough energy and power for driving ranges and acceleration similar to gasoline powered cars. From our design analysis, it can be seen that the cost of aluminum as an anode can be as low as US 1.1/kg as long as the reaction product is recycled. The total fuel efficiency during the cycle process in Al/air electric vehicles (EVs) can be 15% (present stage) or 20% (projected) comparable to that of internal combustion engine vehicles (ICEs) (13%). The design battery energy density is 1300 Wh/kg (present) or 2000 Wh/kg (projected). The cost of battery system chosen to evaluate is US 30/kW (present) or US$ 29/kW (projected). Al/air EVs life-cycle analysis was conducted and compared to lead/acid and nickel metal hydride (NiMH) EVs. Only the Al/air EVs can be projected to have a travel range comparable to ICEs. From this analysis, Al/air EVs are the most promising candidates compared to ICEs in terms of travel range, purchase price, fuel cost, and life-cycle cost.

  2. [The healthiness of the air: historical analysis of the studies on the relationship between health and air pollution in living and working places].

    PubMed

    Riva, M A; Cesana, G C

    2010-01-01

    The relationship between air pollution and health had already been postulated by ancient authors. In the Eighteenth century, Bernardino Ramazzini, the founder of the Occupational Medicine, reported in its works relevant considerations against air pollution and its damages. During the Enlightenment, the studies on the eudiometry conducted by the physic Marsilio Landriani can be considered a first attempt to connect the measurement of air quality to medical issues. In the following centuries, Industrial Revolution and the diffusion of domestic heating were a determining factor in worsening the air quality. Despite specific legislations on smoke abatement, some air pollution "disasters" occurred during the last century. In conclusion, this historical analysis showed the complex evolution of the knowledge on the relationship between health and air pollution. Nowadays, an important contribution to the current scientific and political debate on this issue has been provided also by the Occupational and Environmental Medicine.

  3. Cost Analysis of Outsourcing An Air Force Supply Squadron

    DTIC Science & Technology

    2006-12-01

    Stevens . An Analysis of Industry’s Perspective on the Recent Changes to Circular A-76. Monterey, California: Graduate School of Business & Public Policy...Outsourcing: The OMB Circular A-76 Policy. Washington, D.C: Congressional Research Service, 2005. 164 Brett Stevens . An Analysis of Industry’s...actually lengthen the process. Since the 166 Brett Stevens . An Analysis of Industry’s Perspective on

  4. Analysis of routine communication in the air traffic control system

    NASA Technical Reports Server (NTRS)

    Clark, Herbert H.; Morrow, Daniel; Rodvoid, Michelle

    1990-01-01

    The present project has three related goals. The first is to describe the organization of routine controller-pilot communication. This includes identifying the basic units of communication and how they are organized into discourse, how controllers and pilots use language to achieve their goals, and what topics they discuss. The second goal is to identify the type and frequency of problems that interrupt routine information transfer and prompt pilots and controllers to focus on the communication itself. The authors analyze the costs of these problems in terms of communication efficiency, and the techniques used to resolve these problems. Third, the authors hope to identify factors associated with communication problems, such as deviations from conventional air traffic control procedures.

  5. Analysis of routine communication in the air traffic control system

    NASA Astrophysics Data System (ADS)

    Clark, Herbert H.; Morrow, Daniel; Rodvoid, Michelle

    1990-08-01

    The present project has three related goals. The first is to describe the organization of routine controller-pilot communication. This includes identifying the basic units of communication and how they are organized into discourse, how controllers and pilots use language to achieve their goals, and what topics they discuss. The second goal is to identify the type and frequency of problems that interrupt routine information transfer and prompt pilots and controllers to focus on the communication itself. The authors analyze the costs of these problems in terms of communication efficiency, and the techniques used to resolve these problems. Third, the authors hope to identify factors associated with communication problems, such as deviations from conventional air traffic control procedures.

  6. In Utero Fine Particle Air Pollution and Placental Expression of Genes in the Brain-Derived Neurotrophic Factor Signaling Pathway: An ENVIRONAGE Birth Cohort Study

    PubMed Central

    Saenen, Nelly D.; Plusquin, Michelle; Bijnens, Esmée; Janssen, Bram G.; Gyselaers, Wilfried; Cox, Bianca; Fierens, Frans; Molenberghs, Geert; Penders, Joris; Vrijens, Karen; De Boever, Patrick

    2015-01-01

    Background Developmental processes in the placenta and the fetal brain are shaped by the same biological signals. Recent evidence suggests that adaptive responses of the placenta to the maternal environment may influence central nervous system development. Objectives We studied the association between in utero exposure to fine particle air pollution with a diameter ≤ 2.5 μm (PM2.5) and placental expression of genes implicated in neural development. Methods Expression of 10 target genes in the brain-derived neurotrophic factor (BDNF) signaling pathway were quantified in placental tissue of 90 mother–infant pairs from the ENVIRONAGE birth cohort using quantitative real-time polymerase chain reaction. Trimester-specific PM2.5 exposure levels were estimated for each mother’s home address using a spatiotemporal model. Mixed-effects models were used to evaluate the association between the target genes and PM2.5 exposure measured in different time windows of pregnancy. Results A 5-μg/m3 increase in residential PM2.5 exposure during the first trimester of pregnancy was associated with a 15.9% decrease [95% confidence interval (CI): –28.7, –3.2%, p = 0.015] in expression of placental BDNF at birth. The corresponding estimate for synapsin 1 (SYN1) was a 24.3% decrease (95% CI: –42.8, –5.8%, p = 0.011). Conclusions Placental expression of BDNF and SYN1, two genes implicated in normal neurodevelopmental trajectories, decreased with increasing in utero exposure to PM2.5. Future studies are needed to confirm our findings and evaluate the potential relevance of associations between PM2.5 and placental expression of BDNF and SYN1 on neurodevelopment. We provide the first molecular epidemiological evidence concerning associations between in utero fine particle air pollution exposure and the expression of genes that may influence neurodevelopmental processes. Citation Saenen ND, Plusquin M, Bijnens E, Janssen BG, Gyselaers W, Cox B, Fierens F, Molenberghs G, Penders

  7. Pathway-based factor analysis of gene expression data produces highly heritable phenotypes that associate with age.

    PubMed

    Anand Brown, Andrew; Ding, Zhihao; Viñuela, Ana; Glass, Dan; Parts, Leopold; Spector, Tim; Winn, John; Durbin, Richard

    2015-03-09

    Statistical factor analysis methods have previously been used to remove noise components from high-dimensional data prior to genetic association mapping and, in a guided fashion, to summarize biologically relevant sources of variation. Here, we show how the derived factors summarizing pathway expression can be used to analyze the relationships between expression, heritability, and aging. We used skin gene expression data from 647 twins from the MuTHER Consortium and applied factor analysis to concisely summarize patterns of gene expression to remove broad confounding influences and to produce concise pathway-level phenotypes. We derived 930 "pathway phenotypes" that summarized patterns of variation across 186 KEGG pathways (five phenotypes per pathway). We identified 69 significant associations of age with phenotype from 57 distinct KEGG pathways at a stringent Bonferroni threshold ([Formula: see text]). These phenotypes are more heritable ([Formula: see text]) than gene expression levels. On average, expression levels of 16% of genes within these pathways are associated with age. Several significant pathways relate to metabolizing sugars and fatty acids; others relate to insulin signaling. We have demonstrated that factor analysis methods combined with biological knowledge can produce more reliable phenotypes with less stochastic noise than the individual gene expression levels, which increases our power to discover biologically relevant associations. These phenotypes could also be applied to discover associations with other environmental factors.

  8. Pathway-Based Factor Analysis of Gene Expression Data Produces Highly Heritable Phenotypes That Associate with Age

    PubMed Central

    Anand Brown, Andrew; Ding, Zhihao; Viñuela, Ana; Glass, Dan; Parts, Leopold; Spector, Tim; Winn, John; Durbin, Richard

    2015-01-01

    Statistical factor analysis methods have previously been used to remove noise components from high-dimensional data prior to genetic association mapping and, in a guided fashion, to summarize biologically relevant sources of variation. Here, we show how the derived factors summarizing pathway expression can be used to analyze the relationships between expression, heritability, and aging. We used skin gene expression data from 647 twins from the MuTHER Consortium and applied factor analysis to concisely summarize patterns of gene expression to remove broad confounding influences and to produce concise pathway-level phenotypes. We derived 930 “pathway phenotypes” that summarized patterns of variation across 186 KEGG pathways (five phenotypes per pathway). We identified 69 significant associations of age with phenotype from 57 distinct KEGG pathways at a stringent Bonferroni threshold (P<5.38×10−5). These phenotypes are more heritable (h2=0.32) than gene expression levels. On average, expression levels of 16% of genes within these pathways are associated with age. Several significant pathways relate to metabolizing sugars and fatty acids; others relate to insulin signaling. We have demonstrated that factor analysis methods combined with biological knowledge can produce more reliable phenotypes with less stochastic noise than the individual gene expression levels, which increases our power to discover biologically relevant associations. These phenotypes could also be applied to discover associations with other environmental factors. PMID:25758824

  9. Analysis of expression pathways alterations of Arabidopsis thaliana induced by a Necrosis- and Ethylene-inducing protein

    NASA Astrophysics Data System (ADS)

    Sinigaglia, Marialva; Castro, Mauro A. A.; Echeverrigaray, Sérgio; Pereira, Gonçalo A. G.; Mombach, José C. M.

    2009-10-01

    A major goal in post-genomic biology is the description of physiological functions in terms of gene pathway behavior. In this work, we present the first investigation of expression alterations in ninety-three pathways representing physiological functions of the plant A. thaliana induced by a P. parasitica elicitor (NLPpp) using microarray data publicly available at the AtGenExpress database. Using a novel statistical analysis developed to detect pathway alterations, we identified the gene pathways, hereby called groups of functionally associated genes (defined according to the TAIR/Gene Ontology and other databases), that are significantly altered in response to the elicitor. Instead of looking at individual gene responses, our analysis allowed a detailed characterization of the time ordering of pathways alterations in response to the NLPpp, their physiological implications and specificity. We also observed the activation of genes associated with vesicle trafficking and ROS production implying the initiation of the senescence of the wounded plant tissue.

  10. Pathway Analysis and Modeling of the Differentiation of Human Embryonic Stem Cells into Hepatocyte-like Cells

    NASA Astrophysics Data System (ADS)

    Daskalaki, Andriani; Jozefczuk, Justyna; Lehrach, Hans; Adjaye, James; Wierling, Christoph

    2011-06-01

    A more detailed understanding of the differentiation of human embryonic and induced pluripotent stem cells into hepatocyte-like cells can help to improve therapies for liver diseases, like steatohepatitis. In this work we used microarray-based expression data to analyze the in vitro differentiation of human embryonic stem cells into hepatocytes. Pathway analysis has been carried out on gene expression data of different stages of the differentiation process from embryonic stem cells into hepatocyte-like cells via definitive endoderm and hepatic endoderm. Based on pathway analysis we identified signaling pathways, like the GPCR signaling pathway as well as FOXA2 regulatory networks. Based on these highly enriched pathways we constructed a model prototype to better understand and study the differentiation of stem cells into hepatocytes.

  11. Critical radionuclide/critical pathway analysis for the U.S. Department of Energy's Savannah River Site.

    PubMed

    Jannik, G T

    1999-06-01

    Many different radionuclides have been released to the environment from the Savannah River Site (SRS) during the facility's operational history. However, as shown by this analysis, only a small number of the released radionuclides have been significant contributors to potential doses and risks to off-site people. This article documents the radiological critical contaminant/critical pathway analysis performed for SRS. If site missions and operations remain constant over the next 30 years, only tritium oxide releases are projected to exceed a maximally exposed individual (MEI) risk of 1.0E-06 for either the airborne or liquid pathways. The critical exposure pathways associated with site airborne releases are inhalation and vegetation consumption, whereas the critical exposure pathways associated with liquid releases are drinking water and fish consumption. For the SRS-specific, nontypical exposure pathways (i.e., recreational fishing and deer and hog hunting), cesium-137 is the critical radionuclide.

  12. Pathway Analysis of Metabolic Syndrome Using a Genome-Wide Association Study of Korea Associated Resource (KARE) Cohorts

    PubMed Central

    Shim, Unjin; Kim, Han-Na; Sung, Yeon-Ah

    2014-01-01

    Metabolic syndrome (MetS) is a complex disorder related to insulin resistance, obesity, and inflammation. Genetic and environmental factors also contribute to the development of MetS, and through genome-wide association studies (GWASs), important susceptibility loci have been identified. However, GWASs focus more on individual single-nucleotide polymorphisms (SNPs), explaining only a small portion of genetic heritability. To overcome this limitation, pathway analyses are being applied to GWAS datasets. The aim of this study is to elucidate the biological pathways involved in the pathogenesis of MetS through pathway analysis. Cohort data from the Korea Associated Resource (KARE) was used for analysis, which include 8,842 individuals (age, 52.2 ± 8.9 years; body mass index, 24.6 ± 3.2 kg/m2). A total of 312,121 autosomal SNPs were obtained after quality control. Pathway analysis was conducted using Meta-analysis Gene-Set Enrichment of Variant Associations (MAGENTA) to discover the biological pathways associated with MetS. In the discovery phase, SNPs from chromosome 12, including rs11066280, rs2074356, and rs12229654, were associated with MetS (p < 5 × 10-6), and rs11066280 satisfied the Bonferroni-corrected cutoff (unadjusted p < 1.38 × 10-7, Bonferroni-adjusted p < 0.05). Through pathway analysis, biological pathways, including electron carrier activity, signaling by platelet-derived growth factor (PDGF), the mitogen-activated protein kinase kinase kinase cascade, PDGF binding, peroxisome proliferator-activated receptor (PPAR) signaling, and DNA repair, were associated with MetS. Through pathway analysis of MetS, pathways related with PDGF, mitogen-activated protein kinase, and PPAR signaling, as well as nucleic acid binding, protein secretion, and DNA repair, were identified. Further studies will be needed to clarify the genetic pathogenesis leading to MetS. PMID:25705158

  13. Chemical pathway analysis of the Martian atmosphere: The formation and destruction of ozone

    NASA Astrophysics Data System (ADS)

    Boxe, C.; Stock, J.; Lehmann, R.; Grenfell, L.; Patzer, A.; Rauer, H.; Yung, Y. L.

    2014-12-01

    Ozone is a species of major importance in the Martian atmosphere e.g. since it is involved in the stabilization of Mars' major atmospheric constituent carbon dioxide. Below XX km altitude, ozone acts as an atomic oxygen source, which is produced by photolysis and oxidizes carbon monoxide via catalytic cycles involving odd hydrogen (HOx=H+OH+HO2). Originating mainly from H2O photolysis, odd hydrogen destroys ozone resulting in the observed anti-correlation between water vapor and ozone. Compared with species from the HOx-family, ozone is relatively easy to detect by e.g. UV spectroscopy or IR heterodyne spectroscopy. Similar to carbon dioxide, the concentration of ozone can be critically influenced by chemical trace species acting as catalysts in chemical pathways. The identification of such chemical pathways in complex reaction networks and the quantification of their contribution is in general challenging. Therefore, we use an automated computer algorithm (PAP - Pathway Analysis Program), which is specifically designed to address such problems. In this work, we apply the PAP-algorithm to the results of the newly updated JPL/Caltech photochemical column model of the Martian atmosphere in order to investigate the Martian atmospheric ozone photochemistry. The efficiencies of individual ozone formation and destruction pathways are calculated for different atmospheric heights, by applying the algorithm to each vertical layer of the column model in turn. The results of our investigations suggest that ozone is primarily produced by a Chapman-like mechanism, whereby atomic oxygen is produced by carbon dioxide photolysis instead of molecular oxygen photolysis. In the ozone layer at approximately 40 km altitude, ozone formation is chiefly dominated by a chemical pathway where atomic oxygen is supplied by vertical transport. Ozone consumption pathways involving ozone photolysis are most efficient except for a layer around 40 km altitude where the reaction between ozone and

  14. Signal Propagation in the Human Visual Pathways: An Effective Connectivity Analysis.

    PubMed

    Youssofzadeh, Vahab; Prasad, Girijesh; Fagan, Andrew J; Reilly, Richard B; Martens, Sven; Meaney, James F; Wong-Lin, KongFatt

    2015-09-30

    Although the visual system has been extensively investigated, an integrated account of the spatiotemporal dynamics of long-range signal propagation along the human visual pathways is not completely known or validated. In this work, we used dynamic causal modeling approach to provide insights into the underlying neural circuit dynamics of pattern reversal visual-evoked potentials extracted from concurrent EEG-fMRI data. A recurrent forward-backward connectivity model, consisting of multiple interacting brain regions identified by EEG source localization aided by fMRI spatial priors, best accounted for the data dynamics. Sources were first identified in the thalamic area, primary visual cortex, as well as higher cortical areas along the ventral and dorsal visual processing streams. Consistent with hierarchical early visual processing, the model disclosed and quantified the neural temporal dynamics across the identified activity sources. This signal propagation is dominated by a feedforward process, but we also found weaker effective feedback connectivity. Using effective connectivity analysis, the optimal dynamic causal modeling revealed enhanced connectivity along the dorsal pathway but slightly suppressed connectivity along the ventral pathway. A bias was also found in favor of the right hemisphere consistent with functional attentional asymmetry. This study validates, for the first time, the long-range signal propagation timing in the human visual pathways. A similar modeling approach can potentially be used to understand other cognitive processes and dysfunctions in signal propagation in neurological and neuropsychiatric disorders. Significance statement: An integrated account of long-range visual signal propagation in the human brain is currently incomplete. Using computational neural modeling on our acquired concurrent EEG-fMRI data under a visual evoked task, we found not only a substantial forward propagation toward "higher-order" brain regions but also a

  15. Structural analysis of human FANCL, the E3 ligase in the Fanconi anemia pathway.

    PubMed

    Hodson, Charlotte; Cole, Ambrose R; Lewis, Laurence P C; Miles, Jennifer A; Purkiss, Andrew; Walden, Helen

    2011-09-16

    The Fanconi anemia (FA) pathway is essential for the repair of DNA interstrand cross-links. At the heart of this pathway is the monoubiquitination of the FANCI-FANCD2 (ID) complex by the multiprotein "core complex" containing the E3 ubiquitin ligase FANCL. Vertebrate organisms have the eight-protein core complex, whereas invertebrates apparently do not. We report here the structure of the central domain of human FANCL in comparison with the recently solved Drosophila melanogaster FANCL. Our data represent the first structural detail into the catalytic core of the human system and reveal that the central fold of FANCL is conserved between species. However, there are macromolecular differences between the FANCL proteins that may account for the apparent distinctions in core complex requirements between the vertebrate and invertebrate FA pathways. In addition, we characterize the binding of human FANCL with its partners, Ube2t, FANCD2, and FANCI. Mutational analysis reveals which residues are required for substrate binding, and we also show the domain required for E2 binding.

  16. iTRAQ-based quantitative proteomic analysis of Thermobifida fusca reveals metabolic pathways of cellulose utilization.

    PubMed

    Adav, Sunil S; Ng, Chee Sheng; Sze, Siu Kwan

    2011-09-06

    Thermobifida fusca is an aerobic, thermophilic, cellulose degrading bacterium identified in heated organic materials. This study applied iTRAQ quantitative proteomic analysis to the cellular and membrane proteomes of T. fusca grown in presence and absence of cellulose to elucidate the cellular processes induced by cellulose nutrient. Using an iTRAQ-based quantitative proteomic approach, 783 cytosolic and 181 membrane proteins expressed during cellulose hydrolysis were quantified with ≤1% false discovery rate. The comparative iTRAQ quantification revealed considerable induction in the expression levels and up-regulation of specific proteins in cellulosic medium than non-cellulosic medium. The regulated proteins in cellulosic medium were grouped under central carbohydrate metabolism such as glycolysis/gluconeogenesis, pentose phosphate pathways, citric acid cycle, starch, sugars, pyruvate, propanoate and butanoate metabolism; energy metabolism that includes oxidative phosphorylation, nitrogen, methane and sulfur metabolism; fatty acid metabolism, amino acid metabolic pathways, purine and pyrimidine metabolism, and main cellular genetic information processing functions like replication, transcription, translation, and cell wall synthesis; and environmental information processing (membrane transport and signal transduction). The results demonstrated cellulose induced several metabolic pathways during cellulose utilization.

  17. A novel method for crosstalk analysis of biological networks: improving accuracy of pathway annotation

    PubMed Central

    Ogris, Christoph; Guala, Dimitri; Helleday, Thomas; Sonnhammer, Erik L. L.

    2017-01-01

    Analyzing gene expression patterns is a mainstay to gain functional insights of biological systems. A plethora of tools exist to identify significant enrichment of pathways for a set of differentially expressed genes. Most tools analyze gene overlap between gene sets and are therefore severely hampered by the current state of pathway annotation, yet at the same time they run a high risk of false assignments. A way to improve both true positive and false positive rates (FPRs) is to use a functional association network and instead look for enrichment of network connections between gene sets. We present a new network crosstalk analysis method BinoX that determines the statistical significance of network link enrichment or depletion between gene sets, using the binomial distribution. This is a much more appropriate statistical model than previous methods have employed, and as a result BinoX yields substantially better true positive and FPRs than was possible before. A number of benchmarks were performed to assess the accuracy of BinoX and competing methods. We demonstrate examples of how BinoX finds many biologically meaningful pathway annotations for gene sets from cancer and other diseases, which are not found by other methods. BinoX is available at http://sonnhammer.org/BinoX. PMID:27664219

  18. Metagenomic analysis reveals potential biodegradation pathways of persistent pesticides in freshwater and marine sediments.

    PubMed

    Fang, Hua; Cai, Lin; Yang, Ying; Ju, Feng; Li, Xiangdong; Yu, Yunlong; Zhang, Tong

    2014-02-01

    The abundance and diversity of biodegradation genes (BDGs) and potential degradation pathways of dichlorodiphenyltrichloroethane (DDT), hexachlorocyclohexane (HCH), and atrazine (ATZ) in freshwater and marine sediments were investigated by metagenomic analysis using 6 datasets (16Gb in total). The datasets were derived using Illumina high-throughput sequencing and were based on BLAST against self-established databases of BDGs, DDT degradation genes (DDGs), HCH degradation genes (HDGs), and ATZ degradation genes (ADGs). The results showed that the abundance and diversity of BDGs, DDGs, HDGs, and ADGs varied with sample source and locations. The lip and mnp genes, which encode for peroxidase, and the carA gene, which encodes for laccase, were detected as the dominant genes for degradation of organic pollutants. The hdt, hdg, and atzB genes, which encode for hydratase, dehalogenase, and ethylaminohydrolase, were found to be the most abundant genes involved in DDT, HCH, and ATZ degradation, respectively. The identified 69 genera capable of degrading organic pollutants were mostly affiliated with Proteobacteria (49.3%) and Actinobacteria (21.7%). Four genera, including Plesiocystis, Anaerolinea, Jannaschia, and Mycobacterium, were the major biodegradation populations in all sediments. In this study, the nearly complete biodegradation pathways of DDT and ATZ were found, and the partial degradation pathway of HCH was detected in all sediments.

  19. Pathways of early fatherhood, marriage, and employment: a latent class growth analysis.

    PubMed

    Dariotis, Jacinda K; Pleck, Joseph H; Astone, Nan M; Sonenstein, Freya L

    2011-05-01

    In the National Longitudinal Survey of Youth 1979 (NLSY79), young fathers include heterogeneous subgroups with varying early life pathways in terms of fatherhood timing, the timing of first marriage, and holding full-time employment. Using latent class growth analysis with 10 observations between ages 18 and 37, we derived five latent classes with median ages of first fatherhood below the cohort median (26.4), constituting distinct early fatherhood pathways representing 32.4% of NLSY men: (A) Young Married Fathers, (B) Teen Married Fathers, (C) Young Underemployed Married Fathers, (D) Young Underemployed Single Fathers, and (E) Young Later-Marrying Fathers. A sixth latent class of men who become fathers around the cohort median, following full-time employment and marriage (On-Time On-Sequence Fathers), is the comparison group. With sociodemographic background controlled, all early fatherhood pathways show disadvantage in at least some later-life circumstances (earnings, educational attainment, marital status, and incarceration). The extent of disadvantage is greater when early fatherhood occurs at relatively younger ages (before age 20), occurs outside marriage, or occurs outside full-time employment. The relative disadvantage associated with early fatherhood, unlike early motherhood, increases over the life course.

  20. The technical basis for air pathway assessment of resuspended radioactive aerosols: LLNL experiences at seven sites around the world

    SciTech Connect

    Shinn, J.H.

    1993-09-01

    There is a large uncertainty in quantifying the inhalation pathway and the aerosol emission rate in human health assessments of radioactive-contamination sites. The need for site-specific assessments led to formation of our team of specialists at LLNL, who have participated in numerous field campaigns around the world. Our goal was to obtain all the information necessary for determining potential human exposures and to estimate source terms for turbulent transport of the emissions during both normal and disturbed soil conditions. That is, measurements were made of the key variables to quantify the suspended aerosols at the actual contamination sites, but different scenarios for habitation, site management, and site cleanup were included. The most notable locations of these site-investigations were the Marshall Islands (Bikini, Enewetak, and Rongelap), Nevada Test Site (GMX, Little Feller, Palanquin, and Plutonium Valley), Tonopah (Nevada--site of Roller Coaster), Savannah River Lab (South Carolina--H-Area site), Johnston Island (cleanup of rocket-impact site), Chernobyl (Ukraine--grass field end sandy beach sites near Nuclear Power Plant Unit 4), and Palomares (Spain--site of aircraft accident). This discussion will review the variables quantified, methods developed, general results, uncertainty of estimations, and recommendations for future research that are a result of our experience in these field studies.

  1. Exploring developmental gene toolkit and associated pathways in a potential new model crustacean using transcriptomic analysis.

    PubMed

    Jaramillo, Michael L; Guzman, Frank; Paese, Christian L B; Margis, Rogerio; Nazari, Evelise M; Ammar, Dib; Müller, Yara Maria Rauh

    2016-09-01

    The crustaceans are one of the largest, most diverse, and most successful groups of invertebrates. The diversity among the crustaceans is also reflected in embryonic development models. However, the molecular genetics that regulates embryonic development is not known in those crustaceans that have a short germ-band development with superficial cleavage, such as Macrobrachium olfersi. This species is a freshwater decapod and has great potential to become a model for developmental biology, as well as for evolutionary and environmental studies. To obtain sequence data of M. olfersi from an embryonic developmental perspective, we performed de novo assembly and annotation of the embryonic transcriptome. Using a pooling strategy of total RNA, paired-end Illumina sequencing, and assembly with multiple k-mers, a total of 25,636,097 pair reads were generated. In total, 99,751 unigenes were identified, and 20,893 of these returned a Blastx hit. KEGG pathway analysis mapped a total of 6866 unigenes related to 129 metabolic pathways. In general, 21,845 unigenes were assigned to gene ontology (GO) categories: molecular function (19,604), cellular components (10,254), and biological processes (13,841). Of these, 2142 unigenes were assigned to the developmental process category. More specifically, a total of 35 homologs of embryonic development toolkit genes were identified, which included maternal effect (one gene), gap (six), pair-rule (six), segment polarity (seven), Hox (four), Wnt (eight), and dorsoventral patterning genes (three). In addition, genes of developmental pathways were found, including TGF-β, Wnt, Notch, MAPK, Hedgehog, Jak-STAT, VEGF, and ecdysteroid-inducible nuclear receptors. RT-PCR analysis of eight genes related to embryonic development from gastrulation to late morphogenesis/organogenesis confirmed the applicability of the transcriptome analysis.

  2. Arabidopsis phosphoribosylanthranilate isomerase: molecular genetic analysis of triplicate tryptophan pathway genes.

    PubMed Central

    Li, J; Zhao, J; Rose, A B; Schmidt, R; Last, R L

    1995-01-01

    Phosphoribosylanthranilate isomerase (PAI) catalyzes the third step of the tryptophan biosynthetic pathway. Arabidopsis PAI cDNAs were cloned from a cDNA expression library by complementation of an Escherichia coli trpC- PAI deficiency mutation. Genomic DNA blot hybridization analysis detected three nonallelic genes encoding PAI in the Arabidopsis genome. DNA sequence analysis of cDNA and genomic clones indicated that the PAI1 and PAI2. All three PAI polypeptides possess an N-terminal putative plastid target sequence, suggesting that these enzymes all function in plastids. The PAI1 gene is flanked by nearly identical direct repeats of approximately 350 nucleotides. Our results indicate that, in contrast to most microorganisms, the Arabidopsis PAI protein is not fused with indole-3-glycerolphosphate synthase, which catalyzes the next step in the pathway. Yeast artificial chromosome hybridization studies indicated that the PAI2 gene is tightly linked to the anthranilate synthase alpha subunit 1 (ASA1) gene on chromosome 5. PAI1 was mapped to the top of chromosome 1 using recombinant inbred lines, and PAI3 is loosely linked to PAI1. cDNA restriction mapping and sequencing and RNA gel blot hybridization analysis indicated that all three genes are transcribed in wild-type plants. The expression of antisense PAI1 RNA significantly reduced the immunologically observable PAI protein and enzyme activity in transgenic plants. The plants expressing antisense RNA also showed two phenotypes consistent with a block early in the pathway: blue fluorescence under UV light and resistance to the anthranilate analog 6-methylanthranilate. The extreme nucleotide conservation between the unlinked PAI1 and PAI2 loci suggests that this gene family is actively evolving. PMID:7773017

  3. Design of experiments based variation mode and effect analysis of a conceptual air launched SLV

    NASA Astrophysics Data System (ADS)

    Rafique, Amer Farhan; Zeeshan, Qasim; Kamran, Ali

    2014-12-01

    Conceptual design stage is where the knowledge about the variation in system is still quite vague and herein we intend to analyze and compare various probable design concepts for Air Launched SLV by the use of basic variation mode and effect analysis. In this paper we present a methodology for the Variation Mode and Effect Analysis using Latin Hypercube Sampling based Design of Experiments for the conceptual Air launched Satellite Launch Vehicle. Variations are induced in the Control Variables based on knowledge and experience. The methodology is used to quantify the effect of Noise Factors on the performance of a conceptual Air Launched SLV. The insertion altitude of the Air Launched SLV is the Key Performance Indicator. Preliminary results of the performance and analysis for the simulated experiments are presented here. The performance of the proposed procedure has been tested and, thus, validated by the Air Launched SLV design problem. The Design of Experiment based Variation mode and effect analysis approach is intended for initial conceptual design purposes, thus, providing an immediate insight to the performance of the system in general and quantification of the sensitivity of the key performance indicator in particular, subject to the variations in noise factors prior to the detailed design phase.

  4. Complete genome sequencing and antibiotics biosynthesis pathways analysis of Streptomyces lydicus 103

    PubMed Central

    Jia, Nan; Ding, Ming-Zhu; Luo, Hao; Gao, Feng; Yuan, Ying-Jin

    2017-01-01

    More and more new natural products have been found in Streptomyces species, which become the significant resource for antibiotics production. Among them, Streptomyces lydicus has been known as its ability of streptolydigin biosynthesis. Herein, we present the genome analysis of S. lydicus based on the complete genome sequencing. The circular chromosome of S. lydicus 103 comprises 8,201,357 base pairs with average GC content 72.22%. With the aid of KEGG analysis, we found that S. lydicus 103 can transfer propanoate to succinate, glutamine or glutamate to 2-oxoglutarate, CO2 and L-glutamate to ammonia, which are conducive to the the supply of amino acids. S. lydicus 103 encodes acyl-CoA thioesterase II that takes part in biosynthesis of unsaturated fatty acids, and harbors the complete biosynthesis pathways of lysine, valine, leucine, phenylalanine, tyrosine and isoleucine. Furthermore, a total of 27 putative gene clusters have been predicted to be involved in secondary metabolism, including biosynthesis of streptolydigin, erythromycin, mannopeptimycin, ectoine and desferrioxamine B. Comparative genome analysis of S. lydicus 103 will help us deeply understand its metabolic pathways, which is essential for enhancing the antibiotic production through metabolic engineering. PMID:28317865

  5. Genomic organisation, activity and distribution analysis of the microbial putrescine oxidase degradation pathway.

    PubMed

    Foster, Alexander; Barnes, Nicole; Speight, Robert; Keane, Mark A

    2013-10-01

    The catalytic action of putrescine specific amine oxidases acting in tandem with 4-aminobutyraldehyde dehydrogenase is explored as a degradative pathway in Rhodococcus opacus. By limiting the nitrogen source, increased catalytic activity was induced leading to a coordinated response in the oxidative deamination of putrescine to 4-aminobutyraldehyde and subsequent dehydrogenation to 4-aminobutyrate. Isolating the dehydrogenase by ion exchange chromatography and gel filtration revealed that the enzyme acts principally on linear aliphatic aldehydes possessing an amino moiety. Michaelis-Menten kinetic analysis delivered a Michaelis constant (K(M)=0.014 mM) and maximum rate (Vmax=11.2 μmol/min/mg) for the conversion of 4-aminobutyraldehyde to 4-aminobutyrate. The dehydrogenase identified by MALDI-TOF mass spectrometric analysis (E value=0.031, 23% coverage) belongs to a functionally related genomic cluster that includes the amine oxidase, suggesting their association in a directed cell response. Key regulatory, stress and transport encoding genes have been identified, along with candidate dehydrogenases and transaminases for the further conversion of 4-aminobutyrate to succinate. Genomic analysis has revealed highly similar metabolic gene clustering among members of Actinobacteria, providing insight into putrescine degradation notably among Micrococcaceae, Rhodococci and Corynebacterium by a pathway that was previously uncharacterised in bacteria.

  6. Complete genome sequencing and antibiotics biosynthesis pathways analysis of Streptomyces lydicus 103.

    PubMed

    Jia, Nan; Ding, Ming-Zhu; Luo, Hao; Gao, Feng; Yuan, Ying-Jin

    2017-03-20

    More and more new natural products have been found in Streptomyces species, which become the significant resource for antibiotics production. Among them, Streptomyces lydicus has been known as its ability of streptolydigin biosynthesis. Herein, we present the genome analysis of S. lydicus based on the complete genome sequencing. The circular chromosome of S. lydicus 103 comprises 8,201,357 base pairs with average GC content 72.22%. With the aid of KEGG analysis, we found that S. lydicus 103 can transfer propanoate to succinate, glutamine or glutamate to 2-oxoglutarate, CO2 and L-glutamate to ammonia, which are conducive to the the supply of amino acids. S. lydicus 103 encodes acyl-CoA thioesterase II that takes part in biosynthesis of unsaturated fatty acids, and harbors the complete biosynthesis pathways of lysine, valine, leucine, phenylalanine, tyrosine and isoleucine. Furthermore, a total of 27 putative gene clusters have been predicted to be involved in secondary metabolism, including biosynthesis of streptolydigin, erythromycin, mannopeptimycin, ectoine and desferrioxamine B. Comparative genome analysis of S. lydicus 103 will help us deeply understand its metabolic pathways, which is essential for enhancing the antibiotic production through metabolic engineering.

  7. Aligning ontologies and integrating textual evidence for pathway analysis of microarray data

    SciTech Connect

    Gopalan, Banu; Posse, Christian; Sanfilippo, Antonio P.; Stenzel-Poore, Mary; Stevens, S.L.; Castano, Jose; Beagley, Nathaniel; Riensche, Roderick M.; Baddeley, Bob; Simon, R.P.; Pustejovsky, James

    2006-10-08

    Expression arrays are introducing a paradigmatic change in biology by shifting experimental approaches from single gene studies to genome-level analysis, monitoring the ex-pression levels of several thousands of genes in parallel. The massive amounts of data obtained from the microarray data needs to be integrated and interpreted to infer biological meaning within the context of information-rich pathways. In this paper, we present a methodology that integrates textual information with annotations from cross-referenced ontolo-gies to map genes to pathways in a semi-automated way. We illustrate this approach and compare it favorably to other tools by analyzing the gene expression changes underlying the biological phenomena related to stroke. Stroke is the third leading cause of death and a major disabler in the United States. Through years of study, researchers have amassed a significant knowledge base about stroke, and this knowledge, coupled with new technologies, is providing a wealth of new scientific opportunities. The potential for neu-roprotective stroke therapy is enormous. However, the roles of neurogenesis, angiogenesis, and other proliferative re-sponses in the recovery process following ischemia and the molecular mechanisms that lead to these processes still need to be uncovered. Improved annotation of genomic and pro-teomic data, including annotation of pathways in which genes and proteins are involved, is required to facilitate their interpretation and clinical application. While our approach is not aimed at replacing existing curated pathway databases, it reveals multiple hidden relationships that are not evident with the way these databases analyze functional groupings of genes from the Gene Ontology.

  8. Carbon and chlorine isotope analysis to identify abiotic degradation pathways of 1,1,1-trichloroethane.

    PubMed

    Palau, Jordi; Shouakar-Stash, Orfan; Hunkeler, Daniel

    2014-12-16

    This study investigates dual C-Cl isotope fractionation during 1,1,1-TCA transformation by heat-activated persulfate (PS), hydrolysis/dehydrohalogenation (HY/DH) and Fe(0). Compound-specific chlorine isotope analysis of 1,1,1-TCA was performed for the first time, and transformation-associated isotope fractionation ε bulk C and ε bulk Cl values were -4.0 ± 0.2‰ and no chlorine isotope fractionation with PS, -1.6 ± 0.2‰ and -4.7 ± 0.1‰ for HY/DH, -7.8 ± 0.4‰ and -5.2 ± 0.2‰ with Fe(0). Distinctly different dual isotope slopes (Δδ13C/Δδ37Cl): ∞ with PS, 0.33 ± 0.04 for HY/DH and 1.5 ± 0.1 with Fe(0) highlight the potential of this approach to identify abiotic degradation pathways of 1,1,1-TCA in the field. The trend observed with PS agreed with a C-H bond oxidation mechanism in the first reaction step. For HY/DH and Fe(0) pathways, different slopes were obtained although both pathways involve cleavage of a C-Cl bond in their initial reaction step. In contrast to the expected larger primary carbon isotope effects relative to chlorine for C-Cl bond cleavage, ε bulk C < ε bulk Cl was observed for HY/DH and in a similar range for reduction by Fe(0), suggesting the contribution of secondary chlorine isotope effects. Therefore, different magnitude of secondary chlorine isotope effects could at least be partly responsible for the distinct slopes between HY/DH and Fe(0) pathways. Following this dual isotope approach, abiotic transformation processes can unambiguously be identified and quantified.

  9. Multilocus analysis of SNP and metabolic data within a given pathway

    PubMed Central

    Kristensen, Vessela N; Tsalenko, Anya; Geisler, Jurgen; Faldaas, Anne; Grenaker, Grethe Irene; Lingjærde, Ole Christian; Fjeldstad, Ståle; Yakhini, Zohar; Lønning, Per Eystein; Børresen-Dale, Anne-Lise

    2006-01-01

    Background Complex traits, which are under the influence of multiple and possibly interacting genes, have become a subject of new statistical methodological research. One of the greatest challenges facing human geneticists is the identification and characterization of susceptibility genes for common multifactorial diseases and their association to different quantitative phenotypic traits. Results Two types of data from the same metabolic pathway were used in the analysis: categorical measurements of 18 SNPs; and quantitative measurements of plasma levels of several steroids and their precursors. Using the combinatorial partitioning method we tested various thresholds for each metabolic trait and each individual SNP locus. One SNP in CYP19, 3UTR, two SNPs in CYP1B1 (R48G and A119S) and one in CYP1A1 (T461N) were significantly differently distributed between the high and low level metabolic groups. The leave one out cross validation method showed that 6 SNPs in concert make 65% correct prediction of phenotype. Further we used pattern recognition, computing the p-value by Monte Carlo simulation to identify sets of SNPs and physiological characteristics such as age and weight that contribute to a given metabolic level. Since the SNPs detected by both methods reside either in the same gene (CYP1B1) or in 3 different genes in immediate vicinity on chromosome 15 (CYP19, CYP11 and CYP1A1) we investigated the possibility that they form intragenic and intergenic haplotypes, which may jointly account for a higher activity in the pathway. We identified such haplotypes associated with metabolic levels. Conclusion The methods reported here may enable to study multiple low-penetrance genetic factors that together determine various quantitative phenotypic traits. Our preliminary data suggest that several genes coding for proteins involved in a common pathway, that happen to be located on common chromosomal areas and may form intragenic haplotypes, together account for a higher

  10. Collection and analysis of NASA clean room air samples

    NASA Technical Reports Server (NTRS)

    Sheldon, L. S.; Keever, J.

    1985-01-01

    The environment of the HALOE assembly clean room at NASA Langley Research Center is analyzed to determine the background levels of airborne organic compounds. Sampling is accomplished by pumping the clean room air through absorbing cartridges. For volatile organics, cartridges are thermally desorbed and then analyzed by gas chromatography and mass spectrometry, compounds are identified by searching the EPA/NIH data base using an interactive operator INCOS computer search algorithm. For semivolatile organics, cartridges are solvent entracted and concentrated extracts are analyzed by gas chromatography-electron capture detection, compound identification is made by matching gas chromatogram retention times with known standards. The detection limits for the semivolatile organics are; 0.89 ng cu m for dioctylphlhalate (DOP) and 1.6 ng cu m for polychlorinated biphenyls (PCB). The detection limit for volatile organics ranges from 1 to 50 parts per trillion. Only trace quantities of organics are detected, the DOP levels do not exceed 2.5 ng cu m and the PCB levels do not exceed 454 ng cu m.

  11. Thermogravimetric analysis of rice husks in an air atmosphere

    SciTech Connect

    Mansaray, K.G.; Ghaly, A.E.

    1998-08-01

    In rice-producing countries, large amounts of rice husks are generated as waste material for which there is no ready use and in some cases may have a negative value because of the cost of disposal. Most of these countries depend on fossil fuels for their energy uses, and rice husk can be used to supplement such energy sources using thermochemical conversion processes. However, efficient operation of thermochemical conversion systems requires a thorough understanding of the influence of the influence of the composition and thermal properties of rice husks on their behavior during the conversion process. In this study, the thermal behavior of four rice husk varieties (Lemont, ROK 14, CP 4, and Pa Potho) was examined at three heating rates (10, 20, and 50 C/min) in stationary air atmosphere. The thermal degradation rate in active and passive pyrolysis zones, the initial degradation temperature, and the residual weight at 600 C were determined. Increasing the heating rate increased both the thermal degradation rate and the residual weight and decreased the initial degradation temperature. The higher the cellulosic content of the rice husk, the higher the thermal degradation rate and the initial degradation temperature. Also, higher ash content in the rice husk resulted in higher residual weight at 600 C.

  12. The Use of Sensory Analysis Techniques to Assess the Quality of Indoor Air.

    PubMed

    Lewkowska, Paulina; Dymerski, Tomasz; Gębicki, Jacek; Namieśnik, Jacek

    2017-01-02

    The quality of indoor air is one of the significant elements that influences people's well-being and health inside buildings. Emissions of pollutants, which may cause odor nuisance, are the main reason for people's complaints regarding the quality of indoor air. As a result, it is necessary to perform tests aimed at identifying the sources of odors inside buildings. The article contains basic information on the characteristics of the sources of indoor air pollution and the influence of the odor detection threshold on people's health and comfort. An attempt was also made to classify and use sensory analysis techniques to perform tests of the quality of indoor air, which would enable identification of sensory experience and would allow for indication of the degree of their intensity.

  13. Heat transfer and energy analysis of a solar air collector with smooth plate

    NASA Astrophysics Data System (ADS)

    Chabane, Foued; Moummi, Noureddine

    2014-04-01

    The heat transfer and thermal performance of a single pass solar air heater a smooth plate was investigated experimentally. In the present paper, energy and heat transfer analysis of a solar air collector with smooth plate, this technique is used to determine the optimal thermal performance of flat plate solar air heater by considering the different system and operating parameters to obtain maximum thermal performance. Thermal performance is obtained for different mass flow rate varying in the array 0.0108-0.0202 kg/s with five values, solar intensity; tilt angle and ambient temperature. We discuss the thermal behavior of this type of collector with new design and with my proper construction. An experimental study was carried out on a prototype installed on the experimental tests platform within the University of Biskra in the Algeria. The effects of air mass flow rate, emissivity of channel plates and wind heat transfer coefficient on the accuracy of the criterion are also investigated.

  14. Understanding alternative fluxes/effluxes through comparative metabolic pathway analysis of phylum actinobacteria using a simplified approach.

    PubMed

    Verma, Mansi; Lal, Devi; Saxena, Anjali; Anand, Shailly; Kaur, Jasvinder; Kaur, Jaspreet; Lal, Rup

    2013-12-01

    Actinobacteria are known for their diverse metabolism and physiology. Some are dreadful human pathogens whereas some constitute the natural flora for human gut. Therefore, the understanding of metabolic pathways is a key feature for targeting the pathogenic bacteria without disturbing the symbiotic ones. A big challenge faced today is multiple drug resistance by Mycobacterium and other pathogens that utilize alternative fluxes/effluxes. With the availability of genome sequence, it is now feasible to conduct the comparative in silico analysis. Here we present a simplified approach to compare metabolic pathways so that the species specific enzyme may be traced and engineered for future therapeutics. The analyses of four key carbohydrate metabolic pathways, i.e., glycolysis, pyruvate metabolism, tri carboxylic acid cycle and pentose phosphate pathway suggest the presence of alternative fluxes. It was found that the upper pathway of glycolysis was highly variable in the actinobacterial genomes whereas lower glycolytic pathway was highly conserved. Likewise, pentose phosphate pathway was well conserved in contradiction to TCA cycle, which was found to be incomplete in majority of actinobacteria. The clustering based on presence and absence of genes of these metabolic pathways clearly revealed that members of different genera shared identical pathways and, therefore, provided an easy method to identify the metabolic similarities/differences between pathogenic and symbiotic organisms. The analyses could identify isoenzymes and some key enzymes that were found to be missing in some pathogenic actinobacteria. The present work defines a simple approach to explore the effluxes in four metabolic pathways within the phylum actinobacteria. The analysis clearly reflects that actinobacteria exhibit diverse routes for metabolizing substrates. The pathway comparison can help in finding the enzymes that can be used as drug targets for pathogens without effecting symbiotic organisms

  15. Statistical Analysis of the Impacts of Regional Transportation on the Air Quality in Beijing

    NASA Astrophysics Data System (ADS)

    Huang, Zhongwen; Zhang, Huiling; Tong, Lei; Xiao, Hang

    2016-04-01

    From October to December 2015, Beijing-Tianjin-Hebei (BTH) region had experienced several severe haze events. In order to assess the effects of the regional transportation on the air quality in Beijing, the air monitoring data (PM2.5, SO2, NO2 and CO) from that period published by Chinese National Environmental Monitoring Center (CNEMC) was collected and analyzed with various statistical models. The cities within BTH area were clustered into three groups according to the geographical conditions, while the air pollutant concentrations of cities within a group sharing similar variation trends. The Granger causality test results indicate that significant causal relationships exist between the air pollutant data of Beijing and its surrounding cities (Baoding, Chengde, Tianjin and Zhangjiakou) for the reference period. Then, linear regression models were constructed to capture the interdependency among the multiple time series. It shows that the observed air pollutant concentrations in Beijing were well consistent with the model-fitted results. More importantly, further analysis suggests that the air pollutants in Beijing were strongly affected by regional transportation, as the local sources only contributed 17.88%, 27.12%, 14.63% and 31.36% of PM2.5, SO2, NO2 and CO concentrations, respectively. And the major foreign source for Beijing was from Southwest (Baoding) direction, account for more than 42% of all these air pollutants. Thus, by combining various statistical models, it may not only be able to quickly predict the air qualities of any cities on a regional scale, but also to evaluate the local and regional source contributions for a particular city. Key words: regional transportation, air pollution, Granger causality test, statistical models

  16. Transcriptome analysis of bitter acid biosynthesis and precursor pathways in hop (Humulus lupulus)

    PubMed Central

    2013-01-01

    Background Bitter acids (e.g. humulone) are prenylated polyketides synthesized in lupulin glands of the hop plant (Humulus lupulus) which are important contributors to the bitter flavour and stability of beer. Bitter acids are formed from acyl-CoA precursors derived from branched-chain amino acid (BCAA) degradation and C5 prenyl diphosphates from the methyl-D-erythritol 4-phosphate (MEP) pathway. We used RNA sequencing (RNA-seq) to obtain the transcriptomes of isolated lupulin glands, cones with glands removed and leaves from high α-acid hop cultivars, and analyzed these datasets for genes involved in bitter acid biosynthesis including the supply of major precursors. We also measured the levels of BCAAs, acyl-CoA intermediates, and bitter acids in glands, cones and leaves. Results Transcripts encoding all the enzymes of BCAA metabolism were significantly more abundant in lupulin glands, indicating that BCAA biosynthesis and subsequent degradation occurs in these specialized cells. Branched-chain acyl-CoAs and bitter acids were present at higher levels in glands compared with leaves and cones. RNA-seq analysis showed the gland-specific expression of the MEP pathway, enzymes of sucrose degradation and several transcription factors that may regulate bitter acid biosynthesis in glands. Two branched-chain aminotransferase (BCAT) enzymes, HlBCAT1 and HlBCAT2, were abundant, with gene expression quantification by RNA-seq and qRT-PCR indicating that HlBCAT1 was specific to glands while HlBCAT2 was present in glands, cones and leaves. Recombinant HlBCAT1 and HlBCAT2 catalyzed forward (biosynthetic) and reverse (catabolic) reactions with similar kinetic parameters. HlBCAT1 is targeted to mitochondria where it likely plays a role in BCAA catabolism. HlBCAT2 is a plastidial enzyme likely involved in BCAA biosynthesis. Phylogenetic analysis of the hop BCATs and those from other plants showed that they group into distinct biosynthetic (plastidial) and catabolic (mitochondrial

  17. Identification and pathway analysis of microRNAs with no previous involvement in breast cancer.

    PubMed

    Romero-Cordoba, Sandra; Rodriguez-Cuevas, Sergio; Rebollar-Vega, Rosa; Quintanar-Jurado, Valeria; Maffuz-Aziz, Antonio; Jimenez-Sanchez, Gerardo; Bautista-Piña, Veronica; Arellano-Llamas, Rocio; Hidalgo-Miranda, Alfredo

    2012-01-01

    microRNA expression signatures can differentiate normal and breast cancer tissues and can define specific clinico-pathological phenotypes in breast tumors. In order to further evaluate the microRNA expression profile in breast cancer, we analyzed the expression of 667 microRNAs in 29 tumors and 21 adjacent normal tissues using TaqMan Low-density arrays. 130 miRNAs showed significant differential expression (adjusted P value = 0.05, Fold Change = 2) in breast tumors compared to the normal adjacent tissue. Importantly, the role of 43 of these microRNAs has not been previously reported in breast cancer, including several evolutionary conserved microRNA*, showing similar expression rates to that of their corresponding leading strand. The expression of 14 microRNAs was replicated in an independent set of 55 tumors. Bioinformatic analysis of mRNA targets of the altered miRNAs, identified oncogenes like ERBB2, YY1, several MAP kinases, and known tumor-suppressors like FOXA1 and SMAD4. Pathway analysis identified that some biological process which are important in breast carcinogenesis are affected by the altered microRNA expression, including signaling through MAP kinases and TP53 pathways, as well as biological processes like cell death and communication, focal adhesion and ERBB2-ERBB3 signaling. Our data identified the altered expression of several microRNAs whose aberrant expression might have an important impact on cancer-related cellular pathways and whose role in breast cancer has not been previously described.

  18. Identification and Pathway Analysis of microRNAs with No Previous Involvement in Breast Cancer

    PubMed Central

    Rebollar-Vega, Rosa; Quintanar-Jurado, Valeria; Maffuz-Aziz, Antonio; Jimenez-Sanchez, Gerardo; Bautista-Piña, Veronica; Arellano-Llamas, Rocio; Hidalgo-Miranda, Alfredo

    2012-01-01

    microRNA expression signatures can differentiate normal and breast cancer tissues and can define specific clinico-pathological phenotypes in breast tumors. In order to further evaluate the microRNA expression profile in breast cancer, we analyzed the expression of 667 microRNAs in 29 tumors and 21 adjacent normal tissues using TaqMan Low-density arrays. 130 miRNAs showed significant differential expression (adjusted P value = 0.05, Fold Change = 2) in breast tumors compared to the normal adjacent tissue. Importantly, the role of 43 of these microRNAs has not been previously reported in breast cancer, including several evolutionary conserved microRNA*, showing similar expression rates to that of their corresponding leading strand. The expression of 14 microRNAs was replicated in an independent set of 55 tumors. Bioinformatic analysis of mRNA targets of the altered miRNAs, identified oncogenes like ERBB2, YY1, several MAP kinases, and known tumor-suppressors like FOXA1 and SMAD4. Pathway analysis identified that some biological process which are important in breast carcinogenesis are affected by the altered microRNA expression, including signaling through MAP kinases and TP53 pathways, as well as biological processes like cell death and communication, focal adhesion and ERBB2-ERBB3 signaling. Our data identified the altered expression of several microRNAs whose aberrant expression might have an important impact on cancer-related cellular pathways and whose role in breast cancer has not been previously described. PMID:22438871

  19. A comprehensive analysis of fifteen genes of steviol glycosides biosynthesis pathway in Stevia rebaudiana (Bertoni).

    PubMed

    Kumar, Hitesh; Kaul, Kiran; Bajpai-Gupta, Suphla; Kaul, Vijay Kumar; Kumar, Sanjay

    2012-01-15

    Stevia [Stevia rebuaidana (Bertoni); family: Asteraceae] is known to yield diterpenoid steviol glycosides (SGs), which are about 300 times sweeter than sugar. The present work analyzed the expression of various genes of the SGs biosynthesis pathway in different organs of the plant in relation to the SGs content. Of the various genes of the pathway, SrDXS, SrDXR, SrCPPS, SrKS, SrKO and three glucosyltransferases namely SrUGT85C2, SrUGT74G1 and SrUGT76G1 were reported from stevia. Here, we report cloning of seven additional full-length cDNA sequences namely, SrMCT, SrCMK, SrMDS, SrHDS, SrHDR, SrIDI and SrGGDPS followed by expression analysis of all the fifteen genes vis-à-vis SGs content analysis. SGs content was highest in the leaf at 3rd node position (node position with reference to the apical leaf as the first leaf) as compared to the leaves at other node positions. Except for SrDXR and SrKO, gene expression was maximum in leaf at 1st node and minimum in leaf at 5th node. The expression of SrKO was highest in leaf at 3rd node while in case of SrDXR expression showed an increase up to 3rd leaf and decrease thereafter. SGs accumulated maximum in leaf tissue followed by stem and root, and similar was the pattern of expression of all the fifteen genes. The genes responded to the modulators of the terpenopids biosynthesis. Gibberellin (GA(3)) treatment up-regulated the expression of SrMCT, SrCMK, SrMDS and SrUGT74G1, whereas methyl jasmonate and kinetin treatment down-regulated the expression of all the fifteen genes of the pathway.

  20. Making the Connection: An Air Strategy Analysis Framework

    DTIC Science & Technology

    1995-06-01

    structure of the influential "Strategies to Tasks" analysis tool popularized by General Glenn Kent.37 " Thinking strategically ," as Colonel Warden advocates...of thinking strategically , the airpower Action element is only the means to the end. As Col John Warden says, "After all, we don’t go to war merely

  1. Plasma proteomic analysis of stable coronary artery disease indicates impairment of reverse cholesterol pathway

    PubMed Central

    Basak, Trayambak; Tanwar, Vinay Singh; Bhardwaj, Gourav; Bhardwaj, Nitin; Ahmad, Shadab; Garg, Gaurav; V, Sreenivas; Karthikeyan, Ganesan; Seth, Sandeep; Sengupta, Shantanu

    2016-01-01

    Coronary artery disease (CAD) is one of the largest causes of death worldwide yet the traditional risk factors, although useful in identifying people at high risk, lack the desired predictive accuracy. Techniques like quantitative plasma proteomics holds immense potential to identify newer markers and this study (conducted in three phases) was aimed to identify differentially expressed proteins in stable CAD patients. In the first (discovery) phase, plasma from CAD cases (angiographically proven) and controls were subjected to iTRAQ based proteomic analysis. Proteins found to be differentially expressed were then validated in the second and third (verification and validation) phases in larger number of (n = 546) samples. After multivariate logistic regression adjusting for confounding factors (age, diet, etc.), four proteins involved in the reverse cholesterol pathway (Apo A1, ApoA4, Apo C1 and albumin) along with diabetes and hypertension were found to be significantly associated with CAD and could account for approximately 88% of the cases as revealed by ROC analysis. The maximum odds ratio was found to be 6.70 for albumin (p < 0.0001), followed by Apo AI (5.07, p < 0.0001), Apo CI (4.03, p = 0.001), and Apo AIV (2.63, p = 0.003). Down-regulation of apolipoproteins and albumin implicates the impairment of reverse cholesterol pathway in CAD. PMID:27350024

  2. Plasma proteomic analysis of stable coronary artery disease indicates impairment of reverse cholesterol pathway.

    PubMed

    Basak, Trayambak; Tanwar, Vinay Singh; Bhardwaj, Gourav; Bhardwaj, Nitin; Ahmad, Shadab; Garg, Gaurav; V, Sreenivas; Karthikeyan, Ganesan; Seth, Sandeep; Sengupta, Shantanu

    2016-06-28

    Coronary artery disease (CAD) is one of the largest causes of death worldwide yet the traditional risk factors, although useful in identifying people at high risk, lack the desired predictive accuracy. Techniques like quantitative plasma proteomics holds immense potential to identify newer markers and this study (conducted in three phases) was aimed to identify differentially expressed proteins in stable CAD patients. In the first (discovery) phase, plasma from CAD cases (angiographically proven) and controls were subjected to iTRAQ based proteomic analysis. Proteins found to be differentially expressed were then validated in the second and third (verification and validation) phases in larger number of (n = 546) samples. After multivariate logistic regression adjusting for confounding factors (age, diet, etc.), four proteins involved in the reverse cholesterol pathway (Apo A1, ApoA4, Apo C1 and albumin) along with diabetes and hypertension were found to be significantly associated with CAD and could account for approximately 88% of the cases as revealed by ROC analysis. The maximum odds ratio was found to be 6.70 for albumin (p < 0.0001), followed by Apo AI (5.07, p < 0.0001), Apo CI (4.03, p = 0.001), and Apo AIV (2.63, p = 0.003). Down-regulation of apolipoproteins and albumin implicates the impairment of reverse cholesterol pathway in CAD.

  3. Singularity analysis of the AKT signaling pathway reveals connections between cancer and metabolic diseases

    NASA Astrophysics Data System (ADS)

    Wang, Guanyu

    2010-12-01

    Connections between cancer and metabolic diseases may consist in the complex network of interactions among a common set of biomolecules. By applying singularity and bifurcation analysis, the phenotypes constrained by the AKT signaling pathway are identified and mapped onto the parameter space, which include cancer and certain metabolic diseases. By considering physiologic properties (sensitivity, robustness and adaptivity) the AKT pathway must possess in order to efficiently sense growth factors and nutrients, the region of normal responses is located. To optimize these properties, the intracellular concentration of the AKT protein must be sufficiently high to saturate its enzymes; the strength of the positive feedback must be stronger than that of the negative feedback. The analysis illuminates the parameter space and reveals system-level mechanisms in regulating biological functions (cell growth, survival, proliferation and metabolism) and how their deregulation may lead to the development of diseases. The analytical expressions summarize the synergistic interactions among many molecules, which provides valuable insights into therapeutic interventions. In particular, a strategy for overcoming the limitations of mTOR inhibition is proposed for cancer therapy.

  4. Analysis of the Sonic Hedgehog signaling pathway in normal and abnormal bladder development.

    PubMed

    DeSouza, Kristin R; Saha, Monalee; Carpenter, Ashley R; Scott, Melissa; McHugh, Kirk M

    2013-01-01

    In this study, we examined the expression of Sonic Hedgehog, Patched, Gli1, Gli2, Gli3 and Myocardin in the developing bladders of male and female normal and megabladder (mgb-/-) mutant mice at embryonic days 12 through 16 by in situ hybridization. This analysis indicated that each member of the Sonic Hedgehog signaling pathway as well as Myocardin displayed distinct temporal and spatial patterns of expression during normal bladder development. In contrast, mgb-/- bladders showed both temporal and spatial changes in the expression of Patched, Gli1 and Gli3 as well as a complete lack of Myocardin expression. These changes occurred primarily in the outer mesenchyme of developing mgb-/- bladders consistent with the development of an amuscular bladder phenotype in these animals. These results provide the first comprehensive analysis of the Sonic Hedgehog signaling pathway during normal bladder development and provide strong evidence that this key signaling cascade is critical in establishing radial patterning in the developing bladder. In addition, the lack of detrusor smooth muscle development observed in mgb-/- mice is associated with bladder-specific temporospatial changes in Sonic Hedgehog signaling coupled with a lack of Myocardin expression that appears to result in altered patterning of the outer mesenchyme and poor initiation and differentiation of smooth muscle cells within this region of the developing bladder.

  5. A high-content analysis toolbox permits dissection of diverse signaling pathways for T lymphocyte polarization.

    PubMed

    Freeley, Michael; Bakos, Gabor; Davies, Anthony; Kelleher, Dermot; Long, Aideen; Dunican, Dara J

    2010-06-01

    RNA interfering (RNAi) screening strategies offer the potential to elucidate the signaling pathways that regulate integrin and adhesion receptor-mediated changes in T lymphocyte morphology. Of crucial importance, however, is the definition of key sets of parameters that will provide accurate, quantitative, and nonredundant information to flag relevant hits in such assays. In this study, the authors have used an image-based high-content analysis (HCA) technology platform and a panel of 24 pharmacological inhibitors, at a range of concentrations, to define key sets of parameters that enables sensitive and quantitative effects on integrin (LFA-1)-mediated lymphocyte morphology to be evaluated. In particular, multiparametric analysis of lymphocyte morphology that was based on intracellular staining of both the F-actin and alpha-tubulin cytoskeleton resulted in improved ability to discriminate morphological behavior compared to F-actin staining alone. Morphological and fluorescence intensity/distribution profiling of pharmacologically treated lymphocytes stimulated with integrin (LFA-1) and adhesion receptors (CD44) also revealed notable differences in their sensitivity to inhibitors. The assay described here may be used in HCA strategies such as RNAi screening assays to elucidate the signaling pathways and molecules that regulate integrin/adhesion receptor-mediated T lymphocyte polarization.

  6. Future ozone air quality and radiative forcing over China owing to future changes in emissions under the Representative Concentration Pathways (RCPs)

    NASA Astrophysics Data System (ADS)

    Zhu, Jia; Liao, Hong

    2016-02-01

    We apply the nested grid version of the Goddard Earth Observing System (GEOS) chemical transport model (GEOS-Chem) to assess 2000-2050 changes in O3 air quality and associated radiative forcing in China owing to future changes in emissions under the Representative Concentration Pathways (RCP2.6, RCP4.5, RCP6.0, and RCP8.5). Changes in surface layer O3 concentrations, numbers of O3 exceedance days (days with maximum daily 8 h average (MDA8) O3 exceeding 74.7 ppbv), and tropospheric O3 radiative forcing (RF) are simulated for 2000-2050. Over China, RCP8.5 is the worst scenario for near future (2020-2030) and RCP6.0 is the worst scenario over 2040-2050; the maximum increases in annual mean surface layer O3 concentrations of 6-12 ppbv relative to present day (year 2000) are found over southern China in 2020 and 2030 under RCP8.5 and in 2040 and 2050 under RCP6.0. The numbers of MDA8 O3 exceedance days are simulated to be 10, 0, 0, and 2 days over Beijing-Tianjin-Tanggu (BTT), Yangtze River Delta (YRD), Pearl River Delta (PRD), and Sichuan Basin (SCB), respectively, in the present day (year 2000). No exceedance days are simulated in year 2050 for all the four regions under RCP2.6 and RCP4.5, but extremely high numbers of exceedance days are found in 2050 under RCP6.0 (with 102, 75, 57, and 179 days in BTT, YRD, PRD, and SCB, respectively) and in 2030 under RCP8.5 (with 94, 60, 34, and 162 days in BTT, YRD, PRD, and SCB, respectively). The tropospheric O3 RF in 2050 relative to 2000 averaged over eastern China (18°-45°N, 95°-125°E) is simulated to be -0.11, 0.0, 0.01, and 0.14 W m-2 under RCP2.6, RCP4.5, RCP6.0, and RCP8.5, respectively. When we consider both the health and climate impacts of tropospheric O3 over China in 2050, RCP2.6 is a significantly improving scenario for both air quality and climate, RCP4.5 is a significantly improving scenario for air quality but has small consequences for climate, RCP6.0 is a significantly worsening scenario for air quality

  7. Analysis of hydrogen cyanide in air in a case of attempted cyanide poisoning.

    PubMed

    Magnusson, R; Nyholm, S; Åstot, C

    2012-10-10

    A 32-year-old man attempted to poison his ex-girlfriend with hydrogen cyanide by hiding the pesticide Uragan D2 in her car. During the police investigation, chemical analysis of the air inside the car was performed. Hydrogen cyanide was detected through on-site air analysis using a portable Fourier transform infrared (FTIR) spectroscopy gas analyzer and colorimetric gas detection tubes. Furthermore, impinger air-sampling was performed for off-site sample preparation and analysis by gas chromatography-mass spectrometry (GC-MS). All three independent techniques demonstrated the presence of hydrogen cyanide, at concentrations of 14-20 ppm. Owing to the high volatility of hydrogen cyanide, the temperature and the time since exposure have a substantial effect on the likelihood of detecting hydrogen cyanide at a crime scene. The prevailing conditions (closed space, low temperature) must have supported the preservation of HCN in the car thus enabling the identification even though the analysis was performed several days after the hydrogen cyanide source was removed. This paper demonstrates the applicability of combining on-site FTIR measurements and off-site GC-MS analysis of a crime scene in order to ensure fast detection as well as unambiguous identification for forensic purposes of hydrogen cyanide in air.

  8. Pathway-Based Analysis of a Melanoma Genome-Wide Association Study: Analysis of Genes Related to Tumour-Immunosuppression

    PubMed Central

    Schoof, Nils; Iles, Mark M.; Bishop, D. Timothy; Newton-Bishop, Julia A.; Barrett, Jennifer H.; consortium, GenoMEL

    2011-01-01

    Systemic immunosuppression is a risk factor for melanoma, and sunburn-induced immunosuppression is thought to be causal. Genes in immunosuppression pathways are therefore candidate melanoma-susceptibility genes. If variants within these genes individually have a small effect on disease risk, the association may be undetected in genome-wide association (GWA) studies due to low power to reach a high significance level. Pathway-based approaches have been suggested as a method of incorporating a priori knowledge into the analysis of GWA studies. In this study, the association of 1113 single nucleotide polymorphisms (SNPs) in 43 genes (39 genomic regions) related to immunosuppression have been analysed using a gene-set approach in 1539 melanoma cases and 3917 controls from the GenoMEL consortium GWA study. The association between melanoma susceptibility and the whole set of tumour-immunosuppression genes, and also predefined functional subgroups of genes, was considered. The analysis was based on a measure formed by summing the evidence from the most significant SNP in each gene, and significance was evaluated empirically by case-control label permutation. An association was found between melanoma and the complete set of genes (pemp = 0.002), as well as the subgroups related to the generation of tolerogenic dendritic cells (pemp = 0.006) and secretion of suppressive factors (pemp = 0.0004), thus providing preliminary evidence of involvement of tumour-immunosuppression gene polymorphisms in melanoma susceptibility. The analysis was repeated on a second phase of the GenoMEL study, which showed no evidence of an association. As one of the first attempts to replicate a pathway-level association, our results suggest that low power and heterogeneity may present challenges. PMID:22216283

  9. From elementary flux modes to elementary flux vectors: Metabolic pathway analysis with arbitrary linear flux constraints.

    PubMed

    Klamt, Steffen; Regensburger, Georg; Gerstl, Matthias P; Jungreuthmayer, Christian; Schuster, Stefan; Mahadevan, Radhakrishnan; Zanghellini, Jürgen; Müller, Stefan

    2017-04-01

    Elementary flux modes (EFMs) emerged as a formal concept to describe metabolic pathways and have become an established tool for constraint-based modeling and metabolic network analysis. EFMs are characteristic (support-minimal) vectors of the flux cone that contains all feasible steady-state flux vectors of a given metabolic network. EFMs account for (homogeneous) linear constraints arising from reaction irreversibilities and the assumption of steady state; however, other (inhomogeneous) linear constraints, such as minimal and maximal reaction rates frequently used by other constraint-based techniques (such as flux balance analysis [FBA]), cannot be directly integrated. These additional constraints further restrict the space of feasible flux vectors and turn the flux cone into a general flux polyhedron in which the concept of EFMs is not directly applicable anymore. For this reason, there has been a conceptual gap between EFM-based (pathway) analysis methods and linear optimization (FBA) techniques, as they operate on different geometric objects. One approach to overcome these limitations was proposed ten years ago and is based on the concept of elementary flux vectors (EFVs). Only recently has the community started to recognize the potential of EFVs for metabolic network analysis. In fact, EFVs exactly represent the conceptual development required to generalize the idea of EFMs from flux cones to flux polyhedra. This work aims to present a concise theoretical and practical introduction to EFVs that is accessible to a broad audience. We highlight the close relationship between EFMs and EFVs and demonstrate that almost all applications of EFMs (in flux cones) are possible for EFVs (in flux polyhedra) as well. In fact, certain properties can only be studied with EFVs. Thus, we conclude that EFVs provide a powerful and unifying framework for constraint-based modeling of metabolic networks.

  10. Reflecting Warfighter Needs in Air Force Programs: Prototype Analysis

    DTIC Science & Technology

    2010-01-01

    Helphinstine, Maj Joseph Campo , Maj Johnny Vargas , Scott Kindsvater, and Russell Handy. Late in the project, we also benefited from discussions with Russell... Henry Willis, and Paul Dreyer, “Analytic Tools for Strategic Planning and Investment in the Missile Defense Agency,” in Proceedings of the 3rd Annual...monograph_reports/MR1398/ Willis, Henry , James Bonomo, Paul K. Davis, and Richard Hillestad, Capabilities Analysis Model for Missile Defense (CAM-MD

  11. U. S. (United States) Air Force Fuel Cell Application Analysis.

    DTIC Science & Technology

    1982-01-01

    FUEL CELL POWER UNIT PARAMETERS FOR UNATTENDED REMOTE UNIT - ETHANOL FUELED. . . . . . . . . . . . . . . . . . . . . . . . . 4-3 4-2 FUEL CELL POWER UNIT...4-20 4-4 STATE POINTS - 23 kW ETHANOL - FUELED FCPU. . . ...... 4-23 4 4-5 COMPARATIVE ANALYSIS MX POWER UNIT - DESIGN POINT SELECTION 4...DATA SUMMARY SHEET ETHANOL FUEL CELL POWER UNIT . .... 4-31 4-9 MAJOR COMPONENT DESIGN PARAMETERS - ETHANOL FCPU ........ 4-32 4-10 MAJOR CONTROL

  12. BACT analysis: Are there cost effective air quality benefits from trees?

    SciTech Connect

    McPherson, E.G.; Simpson, J.R.; Scott, K.I.

    1996-12-31

    Trees absorb gaseous pollutants through leaf stomata and can bind or dissolve water soluble pollutants onto moist leaf surfaces. Tree canopies also intercept particulates and reduce local air temperatures. Urban trees may reduce ambient air ozone concentrations, either by direct absorption of ozone or other pollutants such as NO{sub 2}, or by reducing air temperatures, which reduces hydrocarbon emission and ozone formation rates. On the other hand, biogenic hydrocarbon emissions from trees may play a role in ozone formation. The role of trees in air quality has become coupled with concern over the costs and benefits of large-scale urban free planting programs. Air quality management districts provide pollution abatement credits to businesses and institutions by permitting the use of controls or processes, provided they are technically feasible and cost effective, based upon guidelines in Best Available Control Technology (BACT) manuals. Typically BACT analysis is applied to stationary sources, but the authors apply it here to determine if a large-scale urban tree planting can be a cost effective means to improve air quality.

  13. Economic and energetic analysis of capturing CO2 from ambient air

    PubMed Central

    House, Kurt Zenz; Baclig, Antonio C.; Ranjan, Manya; van Nierop, Ernst A.; Wilcox, Jennifer; Herzog, Howard J.

    2011-01-01

    Capturing carbon dioxide from the atmosphere (“air capture”) in an industrial process has been proposed as an option for stabilizing global CO2 concentrations. Published analyses suggest these air capture systems may cost a few hundred dollars per tonne of CO2, making it cost competitive with mainstream CO2 mitigation options like renewable energy, nuclear power, and carbon dioxide capture and storage from large CO2 emitting point sources. We investigate the thermodynamic efficiencies of commercial separation systems as well as trace gas removal systems to better understand and constrain the energy requirements and costs of these air capture systems. Our empirical analyses of operating commercial processes suggest that the energetic and financial costs of capturing CO2 from the air are likely to have been underestimated. Specifically, our analysis of existing gas separation systems suggests that, unless air capture significantly outperforms these systems, it is likely to require more than 400 kJ of work per mole of CO2, requiring it to be powered by CO2-neutral power sources in order to be CO2 negative. We estimate that total system costs of an air capture system will be on the order of $1,000 per tonne of CO2, based on experience with as-built large-scale trace gas removal systems. PMID:22143760

  14. Economic and energetic analysis of capturing CO2 from ambient air.

    PubMed

    House, Kurt Zenz; Baclig, Antonio C; Ranjan, Manya; van Nierop, Ernst A; Wilcox, Jennifer; Herzog, Howard J

    2011-12-20

    Capturing carbon dioxide from the atmosphere ("air capture") in an industrial process has been proposed as an option for stabilizing global CO(2) concentrations. Published analyses suggest these air capture systems may cost a few hundred dollars per tonne of CO(2), making it cost competitive with mainstream CO(2) mitigation options like renewable energy, nuclear power, and carbon dioxide capture and storage from large CO(2) emitting point sources. We investigate the thermodynamic efficiencies of commercial separation systems as well as trace gas removal systems to better understand and constrain the energy requirements and costs of these air capture systems. Our empirical analyses of operating commercial processes suggest that the energetic and financial costs of capturing CO(2) from the air are likely to have been underestimated. Specifically, our analysis of existing gas separation systems suggests that, unless air capture significantly outperforms these systems, it is likely to require more than 400 kJ of work per mole of CO(2), requiring it to be powered by CO(2)-neutral power sources in order to be CO(2) negative. We estimate that total system costs of an air capture system will be on the order of $1,000 per tonne of CO(2), based on experience with as-built large-scale trace gas removal systems.

  15. Heating, ventilating, and air conditioning deactivation thermal analysis of PUREX Plant

    SciTech Connect

    Chen, W.W.; Gregonis, R.A.

    1997-08-01

    Thermal analysis was performed for the proposed Plutonium Uranium Extraction Plant exhaust system after deactivation. The purpose of the analysis was to determine if enough condensation will occur to plug or damage the filtration components. A heat transfer and fluid flow analysis was performed to evaluate the thermal characteristics of the underground duct system, the deep-bed glass fiber filter No. 2, and the high-efficiency particulate air filters in the fourth filter building. The analysis is based on extreme variations of air temperature, relative humidity, and dew point temperature using 15 years of Hanford Site weather data as a basis. The results will be used to evaluate the need for the electric heaters proposed for the canyon exhaust to prevent condensation. Results of the analysis indicate that a condition may exist in the underground ductwork where the duct temperature can lead or lag changes in the ambient air temperature. This condition may contribute to condensation on the inside surfaces of the underground exhaust duct. A worst case conservative analysis was performed assuming that all of the water is removed from the moist air over the inside surface of the concrete duct area in the fully developed turbulent boundary layer while the moist air in the free stream will not condense. The total moisture accumulated in 24 hours is negligible. Water puddling would not be expected. The results of the analyses agree with plant operating experiences. The filters were designed to resist high humidity and direct wetting, filter plugging caused by slight condensation in the upstream duct is not a concern. 19 refs., 2 figs.

  16. Pathway analysis of genome-wide association study data highlights pancreatic development genes as susceptibility factors for pancreatic cancer

    PubMed Central

    Duell, Eric J.; Yu, Kai; Risch, Harvey A.; Olson, Sara H.; Kooperberg, Charles; Wolpin, Brian M.; Jiao, Li; Dong, Xiaoqun; Wheeler, Bill; Arslan, Alan A.; Bueno-de-Mesquita, H. Bas; Fuchs, Charles S.; Gallinger, Steven; Gross, Myron; Hartge, Patricia; Hoover, Robert N.; Holly, Elizabeth A.; Jacobs, Eric J.; Klein, Alison P.; LaCroix, Andrea; Mandelson, Margaret T.; Petersen, Gloria; Zheng, Wei; Agalliu, Ilir; Albanes, Demetrius; Boutron-Ruault, Marie-Christine; Bracci, Paige M.; Buring, Julie E.; Canzian, Federico; Chang, Kenneth; Chanock, Stephen J.; Cotterchio, Michelle; Gaziano, J.Michael; Giovannucci, Edward L.; Goggins, Michael; Hallmans, Göran; Hankinson, Susan E.; Hoffman Bolton, Judith A.; Hunter, David J.; Hutchinson, Amy; Jacobs, Kevin B.; Jenab, Mazda; Khaw, Kay-Tee; Kraft, Peter; Krogh, Vittorio; Kurtz, Robert C.; McWilliams, Robert R.; Mendelsohn, Julie B.; Patel, Alpa V.; Rabe, Kari G.; Riboli, Elio; Shu, Xiao-Ou; Tjønneland, Anne; Tobias, Geoffrey S.; Trichopoulos, Dimitrios; Virtamo, Jarmo; Visvanathan, Kala; Watters, Joanne; Yu, Herbert; Zeleniuch-Jacquotte, Anne; Stolzenberg-Solomon, Rachael Z.

    2012-01-01

    Four loci have been associated with pancreatic cancer through genome-wide association studies (GWAS). Pathway-based analysis of GWAS data is a complementary approach to identify groups of genes or biological pathways enriched with disease-associated single-nucleotide polymorphisms (SNPs) whose individual effect sizes may be too small to be detected by standard single-locus methods. We used the adaptive rank truncated product method in a pathway-based analysis of GWAS data from 3851 pancreatic cancer cases and 3934 control participants pooled from 12 cohort studies and 8 case–control studies (PanScan). We compiled 23 biological pathways hypothesized to be relevant to pancreatic cancer and observed a nominal association between pancreatic cancer and five pathways (P < 0.05), i.e. pancreatic development, Helicobacter pylori lacto/neolacto, hedgehog, Th1/Th2 immune response and apoptosis (P = 2.0 × 10−6, 1.6 × 10−5, 0.0019, 0.019 and 0.023, respectively). After excluding previously identified genes from the original GWAS in three pathways (NR5A2, ABO and SHH), the pancreatic development pathway remained significant (P = 8.3 × 10−5), whereas the others did not. The most significant genes (P < 0.01) in the five pathways were NR5A2, HNF1A, HNF4G and PDX1 for pancreatic development; ABO for H. pylori lacto/neolacto; SHH for hedgehog; TGFBR2 and CCL18 for Th1/Th2 immune response and MAPK8 and BCL2L11 for apoptosis. Our results provide a link between inherited variation in genes important for pancreatic development and cancer and show that pathway-based approaches to analysis of GWAS data can yield important insights into the collective role of genetic risk variants in cancer. PMID:22523087

  17. The Application of Decision Analysis Methods to Source Selection in the United States Air Force

    DTIC Science & Technology

    1991-08-01

    Specifically, Multiattribute Utility Theory (MAUT) and the Analytic Hierarchy Process (AHP) are applied to source selection within the United States Air... Multiattribute Utility Theory , Analytic 137 Heirarchy Process, Source Selection, System Acquisition 16. PRICE CODE 17. SECURITY CLASSIFICATION 18 SECURITY...decision analysis methods to the selection of the ’best" contractor for defense systems acquisition. Specifically, Multiattribute Utility Theory (MAUT

  18. Internal air flow analysis of a bladeless micro aerial vehicle hemisphere body using computational fluid dynamic

    NASA Astrophysics Data System (ADS)

    Othman, M. N. K.; Zuradzman, M. Razlan; Hazry, D.; Khairunizam, Wan; Shahriman, A. B.; Yaacob, S.; Ahmed, S. Faiz; Hussain, Abadalsalam T.

    2014-12-01

    This paper explain the analysis of internal air flow velocity of a bladeless vertical takeoff and landing (VTOL) Micro Aerial Vehicle (MAV) hemisphere body. In mechanical design, before produce a prototype model, several analyses should be done to ensure the product's effectiveness and efficiency. There are two types of analysis method can be done in mechanical design; mathematical modeling and computational fluid dynamic. In this analysis, I used computational fluid dynamic (CFD) by using SolidWorks Flow Simulation software. The idea came through to overcome the problem of ordinary quadrotor UAV which has larger size due to using four rotors and the propellers are exposed to environment. The bladeless MAV body is designed to protect all electronic parts, which means it can be used in rainy condition. It also has been made to increase the thrust produced by the ducted propeller compare to exposed propeller. From the analysis result, the air flow velocity at the ducted area increased to twice the inlet air. This means that the duct contribute to the increasing of air velocity.

  19. Internal air flow analysis of a bladeless micro aerial vehicle hemisphere body using computational fluid dynamic

    SciTech Connect

    Othman, M. N. K. E-mail: zuradzman@unimap.edu.my E-mail: khairunizam@unimap.edu.my E-mail: s.yaacob@unimap.edu.my E-mail: abadal@unimap.edu.my; Zuradzman, M. Razlan E-mail: zuradzman@unimap.edu.my E-mail: khairunizam@unimap.edu.my E-mail: s.yaacob@unimap.edu.my E-mail: abadal@unimap.edu.my; Hazry, D. E-mail: zuradzman@unimap.edu.my E-mail: khairunizam@unimap.edu.my E-mail: s.yaacob@unimap.edu.my E-mail: abadal@unimap.edu.my; Khairunizam, Wan E-mail: zuradzman@unimap.edu.my E-mail: khairunizam@unimap.edu.my E-mail: s.yaacob@unimap.edu.my E-mail: abadal@unimap.edu.my; Shahriman, A. B. E-mail: zuradzman@unimap.edu.my E-mail: khairunizam@unimap.edu.my E-mail: s.yaacob@unimap.edu.my E-mail: abadal@unimap.edu.my; Yaacob, S. E-mail: zuradzman@unimap.edu.my E-mail: khairunizam@unimap.edu.my E-mail: s.yaacob@unimap.edu.my E-mail: abadal@unimap.edu.my; Ahmed, S. Faiz E-mail: zuradzman@unimap.edu.my E-mail: khairunizam@unimap.edu.my E-mail: s.yaacob@unimap.edu.my E-mail: abadal@unimap.edu.my; and others

    2014-12-04

    This paper explain the analysis of internal air flow velocity of a bladeless vertical takeoff and landing (VTOL) Micro Aerial Vehicle (MAV) hemisphere body. In mechanical design, before produce a prototype model, several analyses should be done to ensure the product's effectiveness and efficiency. There are two types of analysis method can be done in mechanical design; mathematical modeling and computational fluid dynamic. In this analysis, I used computational fluid dynamic (CFD) by using SolidWorks Flow Simulation software. The idea came through to overcome the problem of ordinary quadrotor UAV which has larger size due to using four rotors and the propellers are exposed to environment. The bladeless MAV body is designed to protect all electronic parts, which means it can be used in rainy condition. It also has been made to increase the thrust produced by the ducted propeller compare to exposed propeller. From the analysis result, the air flow velocity at the ducted area increased to twice the inlet air. This means that the duct contribute to the increasing of air velocity.

  20. An Analysis of Skill Requirements for Operators of Amphibious Air Cushion Vehicles (ACVs).

    ERIC Educational Resources Information Center

    McKnight, A. James; And Others

    This report describes the skills required in the operation of an amphibious air cushion vehicle (ACV) in Army tactical and logistic missions. The research involved analyzing ACV characteristics, operating requirements, environmental effects, and results of a simulation experiment. The analysis indicates that ACV operation is complicated by an…

  1. Separating the Air Quality Impact of a Major Highway and Nearby Sources by Nonparametric Trajectory Analysis

    EPA Science Inventory

    Nonparametric Trajectory Analysis (NTA), a receptor-oriented model, was used to assess the impact of local sources of air pollution at monitoring sites located adjacent to highway I-15 in Las Vegas, NV. Measurements of black carbon, carbon monoxide, nitrogen oxides, and sulfur di...

  2. Scenarios for the Future of Air Quality: Planning and Analysis in an Uncertain World

    EPA Science Inventory

    On November 15 and 16 of 2010, EPA hosted a workshop: The Future of Air Quality: Planning and Analysis in An Uncertain World in Chapel Hill, North Carolina. This workshop was an “outside-of-the-box” thinking exercise, where a small group of EPA staff and managers brainstormed o...

  3. An Historical Analysis of the United States Naval Academy Graduates in the United States Air Force.

    ERIC Educational Resources Information Center

    Hodge, William E.

    The purpose of the study is to provide an analysis of the Naval Academy graduates who were commissioned in the Air Force upon graduation. Active duty personnel records were searched to determine retention, rank, professional military education, education level and career field assignments. Comparisons were made between this group and the regular…

  4. A STRINGENT COMPARISON OF SAMPLING AND ANALYSIS METHODS FOR VOCS IN AMBIENT AIR

    EPA Science Inventory

    A carefully designed study was conducted during the summer of 1998 to simultaneously collect samples of ambient air by canisters and compare the analysis results to direct sorbent preconcentration results taken at the time of sample collection. A total of 32 1-h sample sets we...

  5. Comparative Analysis of Leasing versus Buying General Purpose Vehicles (Sedan) in the Korean Air Force

    DTIC Science & Technology

    2002-03-01

    COMPARATIVE ANALYSIS OF LEASING VERSUS BUYING GENERAL PURPOSE VEHICLES (SEDAN) IN THE KOREAN AIR FORCE...leasing versus buying vehicle study started from the recognition of this situation in which ROKAF needs an efficient and effective vehicle procurement...versus buying vehicles , which has been used in buying versus leasing decision. This research analyzed two variables, logistics benefits and costs, and

  6. FORMAL UNCERTAINTY ANALYSIS OF A LAGRANGIAN PHOTOCHEMICAL AIR POLLUTION MODEL. (R824792)

    EPA Science Inventory

    This study applied Monte Carlo analysis with Latin
    hypercube sampling to evaluate the effects of uncertainty
    in air parcel trajectory paths, emissions, rate constants,
    deposition affinities, mixing heights, and atmospheric stability
    on predictions from a vertically...

  7. Analysis of feature selection with Probabilistic Neural Network (PNN) to classify sources influencing indoor air quality

    NASA Astrophysics Data System (ADS)

    Saad, S. M.; Shakaff, A. Y. M.; Saad, A. R. M.; Yusof, A. M.; Andrew, A. M.; Zakaria, A.; Adom, A. H.

    2017-03-01

    There are various sources influencing indoor air quality (IAQ) which could emit dangerous gases such as carbon monoxide (CO), carbon dioxide (CO2), ozone (O3) and particulate matter. These gases are usually safe for us to breathe in if they are emitted in safe quantity but if the amount of these gases exceeded the safe level, they might be hazardous to human being especially children and people with asthmatic problem. Therefore, a smart indoor air quality monitoring system (IAQMS) is needed that able to tell the occupants about which sources that trigger the indoor air pollution. In this project, an IAQMS that able to classify sources influencing IAQ has been developed. This IAQMS applies a classification method based on Probabilistic Neural Network (PNN). It is used to classify the sources of indoor air pollution based on five conditions: ambient air, human activity, presence of chemical products, presence of food and beverage, and presence of fragrance. In order to get good and best classification accuracy, an analysis of several feature selection based on data pre-processing method is done to discriminate among the sources. The output from each data pre-processing method has been used as the input for the neural network. The result shows that PNN analysis with the data pre-processing method give good classification accuracy of 99.89% and able to classify the sources influencing IAQ high classification rate.

  8. Regression analysis in modeling of air surface temperature and factors affecting its value in Peninsular Malaysia

    NASA Astrophysics Data System (ADS)

    Rajab, Jasim Mohammed; Jafri, Mohd. Zubir Mat; Lim, Hwee San; Abdullah, Khiruddin

    2012-10-01

    This study encompasses air surface temperature (AST) modeling in the lower atmosphere. Data of four atmosphere pollutant gases (CO, O3, CH4, and H2O) dataset, retrieved from the National Aeronautics and Space Administration Atmospheric Infrared Sounder (AIRS), from 2003 to 2008 was employed to develop a model to predict AST value in the Malaysian peninsula using the multiple regression method. For the entire period, the pollutants were highly correlated (R=0.821) with predicted AST. Comparisons among five stations in 2009 showed close agreement between the predicted AST and the observed AST from AIRS, especially in the southwest monsoon (SWM) season, within 1.3 K, and for in situ data, within 1 to 2 K. The validation results of AST with AST from AIRS showed high correlation coefficient (R=0.845 to 0.918), indicating the model's efficiency and accuracy. Statistical analysis in terms of β showed that H2O (0.565 to 1.746) tended to contribute significantly to high AST values during the northeast monsoon season. Generally, these results clearly indicate the advantage of using the satellite AIRS data and a correlation analysis study to investigate the impact of atmospheric greenhouse gases on AST over the Malaysian peninsula. A model was developed that is capable of retrieving the Malaysian peninsulan AST in all weather conditions, with total uncertainties ranging between 1 and 2 K.

  9. Putative drug and vaccine target protein identification using comparative genomic analysis of KEGG annotated metabolic pathways of Mycoplasma hyopneumoniae.

    PubMed

    Damte, Dereje; Suh, Joo-Won; Lee, Seung-Jin; Yohannes, Sileshi Belew; Hossain, Md Akil; Park, Seung-Chun

    2013-07-01

    In the present study, a computational comparative and subtractive genomic/proteomic analysis aimed at the identification of putative therapeutic target and vaccine candidate proteins from Kyoto Encyclopedia of Genes and Genomes (KEGG) annotated metabolic pathways of Mycoplasma hyopneumoniae was performed for drug design and vaccine production pipelines against M.hyopneumoniae. The employed comparative genomic and metabolic pathway analysis with a predefined computational systemic workflow extracted a total of 41 annotated metabolic pathways from KEGG among which five were unique to M. hyopneumoniae. A total of 234 proteins were identified to be involved in these metabolic pathways. Although 125 non homologous and predicted essential proteins were found from the total that could serve as potential drug targets and vaccine candidates, additional prioritizing parameters characterize 21 proteins as vaccine candidate while druggability of each of the identified proteins evaluated by the DrugBank database prioritized 42 proteins suitable for drug targets.

  10. Using Social Media to Detect Outdoor Air Pollution and Monitor Air Quality Index (AQI): A Geo-Targeted Spatiotemporal Analysis Framework with Sina Weibo (Chinese Twitter)

    PubMed Central

    Tsou, Ming-Hsiang; Fu, Xiaokang

    2015-01-01

    Outdoor air pollution is a serious problem in many developing countries today. This study focuses on monitoring the dynamic changes of air quality effectively in large cities by analyzing the spatiotemporal trends in geo-targeted social media messages with comprehensive big data filtering procedures. We introduce a new social media analytic framework to (1) investigate the relationship between air pollution topics posted in Sina Weibo (Chinese Twitter) and the daily Air Quality Index (AQI) published by China’s Ministry of Environmental Protection; and (2) monitor the dynamics of air quality index by using social media messages. Correlation analysis was used to compare the connections between discussion trends in social media messages and the temporal changes in the AQI during 2012. We categorized relevant messages into three types, retweets, mobile app messages, and original individual messages finding that original individual messages had the highest correlation to the Air Quality Index. Based on this correlation analysis, individual messages were used to monitor the AQI in 2013. Our study indicates that the filtered social media messages are strongly correlated to the AQI and can be used to monitor the air quality dynamics to some extent. PMID:26505756

  11. An Approach for Identification of Novel Drug Targets in Streptococcus pyogenes SF370 Through Pathway Analysis.

    PubMed

    Singh, Satendra; Singh, Dev Bukhsh; Singh, Anamika; Gautam, Budhayash; Ram, Gurudayal; Dwivedi, Seema; Ramteke, Pramod W

    2016-12-01

    Streptococcus pyogenes is one of the most important pathogens as it is involved in various infections affecting upper respiratory tract and skin. Due to the emergence of multidrug resistance and cross-resistance, S. Pyogenes is becoming more pathogenic and dangerous. In the present study, an in silico comparative analysis of total 65 metabolic pathways of the host (Homo sapiens) and the pathogen was performed. Initially, 486 paralogous enzymes were identified so that they can be removed from possible drug target list. The 105 enzymes of the biochemical pathways of S. pyogenes from the KEGG metabolic pathway database were compared with the proteins from the Homo sapiens by performing a BLASTP search against the non-redundant database restricted to the Homo sapiens subset. Out of these, 83 enzymes were identified as non-human homologous while 30 enzymes of inadequate amino acid length were removed for further processing. Essential enzymes were finally mined from remaining 53 enzymes. Finally, 28 essential enzymes were identified in S. pyogenes SF370 (serotype M1). In subcellular localization study, 18 enzymes were predicted with cytoplasmic localization and ten enzymes with the membrane localization. These ten enzymes with putative membrane localization should be of particular interest. Acyl-carrier-protein S-malonyltransferase, DNA polymerase III subunit beta and dihydropteroate synthase are novel drug targets and thus can be used to design potential inhibitors against S. pyogenes infection. 3D structure of dihydropteroate synthase was modeled and validated that can be used for virtual screening and interaction study of potential inhibitors with the target enzyme.

  12. Systems Analysis of Adaptive Responses to MAP Kinase Pathway Blockade in BRAF Mutant Melanoma

    PubMed Central

    Capaldo, Brian J.; Roller, Devin; Axelrod, Mark J.; Koeppel, Alex F.; Petricoin, Emanuel F.; Slingluff, Craig L.; Weber, Michael J.; Mackey, Aaron J.; Gioeli, Daniel; Bekiranov, Stefan

    2015-01-01

    Fifty percent of cutaneous melanomas are driven by activated BRAFV600E, but tumors treated with RAF inhibitors, even when they respond dramatically, rapidly adapt and develop resistance. Thus, there is a pressing need to identify the major mechanisms of intrinsic and adaptive resistance and develop drug combinations that target these resistance mechanisms. In a combinatorial drug screen on a panel of 12 treatment-naïve BRAFV600E mutant melanoma cell lines of varying levels of resistance to mitogen-activated protein kinase (MAPK) pathway inhibition, we identified the combination of PLX4720, a targeted inhibitor of mutated BRaf, and lapatinib, an inhibitor of the ErbB family of receptor tyrosine kinases, as synergistically cytotoxic in the subset of cell lines that displayed the most resistance to PLX4720. To identify potential mechanisms of resistance to PLX4720 treatment and synergy with lapatinib treatment, we performed a multi-platform functional genomics analysis to profile the genome as well as the transcriptional and proteomic responses of these cell lines to treatment with PLX4720. We found modest levels of resistance correlated with the zygosity of the BRAF V600E allele and receptor tyrosine kinase (RTK) mutational status. Layered over base-line resistance was substantial upregulation of many ErbB pathway genes in response to BRaf inhibition, thus generating the vulnerability to combination with lapatinib. The transcriptional responses of ErbB pathway genes are associated with a number of transcription factors, including ETS2 and its associated cofactors that represent a convergent regulatory mechanism conferring synergistic drug susceptibility in the context of diverse mutational landscapes. PMID:26405815

  13. Systems Level Analysis and Identification of Pathways and Networks Associated with Liver Fibrosis

    PubMed Central

    AbdulHameed, Mohamed Diwan M.; Tawa, Gregory J.; Kumar, Kamal; Ippolito, Danielle L.; Lewis, John A.; Stallings, Jonathan D.; Wallqvist, Anders

    2014-01-01

    Toxic liver injury causes necrosis and fibrosis, which may lead to cirrhosis and liver failure. Despite recent progress in understanding the mechanism of liver fibrosis, our knowledge of the molecular-level details of this disease is still incomplete. The elucidation of networks and pathways associated with liver fibrosis can provide insight into the underlying molecular mechanisms of the disease, as well as identify potential diagnostic or prognostic biomarkers. Towards this end, we analyzed rat gene expression data from a range of chemical exposures that produced observable periportal liver fibrosis as documented in DrugMatrix, a publicly available toxicogenomics database. We identified genes relevant to liver fibrosis using standard differential expression and co-expression analyses, and then used these genes in pathway enrichment and protein-protein interaction (PPI) network analyses. We identified a PPI network module associated with liver fibrosis that includes known liver fibrosis-relevant genes, such as tissue inhibitor of metalloproteinase-1, galectin-3, connective tissue growth factor, and lipocalin-2. We also identified several new genes, such as perilipin-3, legumain, and myocilin, which were associated with liver fibrosis. We further analyzed the expression pattern of the genes in the PPI network module across a wide range of 640 chemical exposure conditions in DrugMatrix and identified early indications of liver fibrosis for carbon tetrachloride and lipopolysaccharide exposures. Although it is well known that carbon tetrachloride and lipopolysaccharide can cause liver fibrosis, our network analysis was able to link these compounds to potential fibrotic damage before histopathological changes associated with liver fibrosis appeared. These results demonstrated that our approach is capable of identifying early-stage indicators of liver fibrosis and underscore its potential to aid in predictive toxicity, biomarker identification, and to generally identify

  14. In silico pathway analysis in cervical carcinoma reveals potential new targets for treatment

    PubMed Central

    van Dam, Peter A.; van Dam, Pieter-Jan H. H.; Rolfo, Christian; Giallombardo, Marco; van Berckelaer, Christophe; Trinh, Xuan Bich; Altintas, Sevilay; Huizing, Manon; Papadimitriou, Kostas; Tjalma, Wiebren A. A.; van Laere, Steven

    2016-01-01

    An in silico pathway analysis was performed in order to improve current knowledge on the molecular drivers of cervical cancer and detect potential targets for treatment. Three publicly available Affymetrix gene expression data-sets (GSE5787, GSE7803, GSE9750) were retrieved, vouching for a total of 9 cervical cancer cell lines (CCCLs), 39 normal cervical samples, 7 CIN3 samples and 111 cervical cancer samples (CCSs). Predication analysis of microarrays was performed in the Affymetrix sets to identify cervical cancer biomarkers. To select cancer cell-specific genes the CCSs were compared to the CCCLs. Validated genes were submitted to a gene set enrichment analysis (GSEA) and Expression2Kinases (E2K). In the CCSs a total of 1,547 probe sets were identified that were overexpressed (FDR < 0.1). Comparing to CCCLs 560 probe sets (481 unique genes) had a cancer cell-specific expression profile, and 315 of these genes (65%) were validated. GSEA identified 5 cancer hallmarks enriched in CCSs (P < 0.01 and FDR < 0.25) showing that deregulation of the cell cycle is a major component of cervical cancer biology. E2K identified a protein-protein interaction (PPI) network of 162 nodes (including 20 drugable kinases) and 1626 edges. This PPI-network consists of 5 signaling modules associated with MYC signaling (Module 1), cell cycle deregulation (Module 2), TGFβ-signaling (Module 3), MAPK signaling (Module 4) and chromatin modeling (Module 5). Potential targets for treatment which could be identified were CDK1, CDK2, ABL1, ATM, AKT1, MAPK1, MAPK3 among others. The present study identified important driver pathways in cervical carcinogenesis which should be assessed for their potential therapeutic drugability. PMID:26701206

  15. An air photo analysis of an airplane crash.

    PubMed

    Rinker, J N; Garstang, J H; Edwards, D; Del Vecchio, J J

    1989-07-01

    Crash patterns-such as cut and damaged vegetation, gouges, debris scatter, burn areas, etc.,-and their spatial relations can be very effectively evaluated by the analysis of stereo aerial photographs. Results from the Canadian Aviation Safety Board's use of aerial photography in the Gander, Nfld., crash of Dec. 12, 1985, show that the technique can lend direct support to an investigation in several ways. It provides an overall perspective view of the regional relations of the crash patterns. It helps direct ground activities. In three-covered areas, it can help establish aircraft attitude and orientation. When combined with debris plots and attitude determinations, it can help establish the breakup sequence. And, when coupled to photogrammetric procedures, it can assign dimensional values to attitude, descent path, areas, lengths, etc.

  16. Microbial community analysis in biotrickling filters treating isopropanol air emissions.

    PubMed

    Pérez, M Carmen; Alvarez-Hornos, F Javier; San-Valero, Pau; Marzal, Paula; Gabaldón, Carmen

    2013-01-01

    The evolution of the microbial community was analysed over one year in two biotrickling filters operating under intermittent feeding conditions and treating isopropanol emissions, a pollutant typically found in the flexography sector. Each reactor was packed with one media: plastic cross-flow-structured material or polypropylene rings. The communities were monitored by fluorescence in situ hybridization (FISH) and denaturing gradient gel electrophoresis (DGGE) analysis of the 16S rRNA region. After inoculation with activated sludge, the biotrickling filters were operated using inlet loads (ILs) from 20 to 65 g C m(-3) h(-1) and empty-bed residence times (EBRTs) from 14 to 160 s. Removal efficiencies higher than 80% were obtained with ILs up to 35 g C m(-3) h(-1) working at EBRTs as low as 24 s. There was an increase in the total percentage of the target domains of up to around 80% at the end of the experiment. Specifically, the Gammaproteobacteria domain group, which includes the well-known volatile organic compound (VOC)-degrading species such as Pseudomonas putida, showed a noticeable rise in the two biotrickling filters of 26% and 27%, respectively. DGGE pattern band analysis revealed a stable band of Pseudomonas putida in all the samples monitored, even in the lower diversity communities. In addition, at similar operational conditions, the biotrickling filter with a greater relative abundance of Pseudomonas sp. (19.2% vs. 8%) showed higher removal efficiency (90% vs. 79%). Results indicate the importance of undertaking a further in-depth study of the involved species in the biofiltration process and their specific function.

  17. Traffic-related air pollution and lung cancer: A meta-analysis

    PubMed Central

    Chen, Gongbo; Wan, Xia; Yang, Gonghuan; Zou, Xiaonong

    2015-01-01

    Background We conducted a meta-analysis to evaluate the association between traffic-related air pollution and lung cancer in order to provide evidence for control of traffic-related air pollution. Methods Several databases were searched for relevant studies up to December 2013. The quality of articles obtained was evaluated by the Strengthening the Reporting of Observational Studies in Epidemiology checklist. Statistical analysis, including pooling effective sizes and confidential intervals, was performed. Results A total of 1106 records were obtained through the database and 36 studies were included in our analysis. Among the studies included, 14 evaluated the association between ambient exposure to traffic-related air pollution and lung cancer and 22 studies involved occupational exposure to air pollution among professional drivers. Twenty-two studies were marked A level regarding quality, 13 were B level, and one was C level. Exposure to nitrogen dioxide (meta-odds ratio [OR]: 1.06, 95% confidence interval [CI]: 0.99–1.13), nitrogen oxide (meta-OR: 1.04, 95% CI: 1.01–1.07), sulfur dioxide (meta-OR: 1.03, 95% CI: 1.02–1.05), and fine particulate matter (meta-OR: 1.11, 95% CI: 1.00–1.22) were positively associated with a risk of lung cancer. Occupational exposure to air pollution among professional drivers significantly increased the incidence (meta-OR: 1.27, 95% CI: 1.19–1.36) and mortality of lung cancer (meta-OR: 1.14, 95% CI: 1.04–1.26). Conclusion Exposure to traffic-related air pollution significantly increased the risk of lung cancer. PMID:26273377

  18. Aging Chart: a community resource for rapid exploratory pathway analysis of age-related processes

    PubMed Central

    Moskalev, Alexey; Zhikrivetskaya, Svetlana; Shaposhnikov, Mikhail; Dobrovolskaya, Evgenia; Gurinovich, Roman; Kuryan, Oleg; Pashuk, Aleksandr; Jellen, Leslie C.; Aliper, Alex; Peregudov, Alex; Zhavoronkov, Alex

    2016-01-01

    Aging research is a multi-disciplinary field encompassing knowledge from many areas of basic, applied and clinical research. Age-related processes occur on molecular, cellular, tissue, organ, system, organismal and even psychological levels, trigger the onset of multiple debilitating diseases and lead to a loss of function, and there is a need for a unified knowledge repository designed to track, analyze and visualize the cause and effect relationships and interactions between the many elements and processes on all levels. Aging Chart (http://agingchart.org/) is a new, community-curated collection of aging pathways and knowledge that provides a platform for rapid exploratory analysis. Building on an initial content base constructed by a team of experts from peer-reviewed literature, users can integrate new data into biological pathway diagrams for a visible, intuitive, top-down framework of aging processes that fosters knowledge-building and collaboration. As the body of knowledge in aging research is rapidly increasing, an open visual encyclopedia of aging processes will be useful to both the new entrants and experts in the field. PMID:26602690

  19. Proteomic analysis of the postsynaptic density implicates synaptic function and energy pathways in bipolar disorder

    PubMed Central

    Föcking, M; Dicker, P; Lopez, L M; Hryniewiecka, M; Wynne, K; English, J A; Cagney, G; Cotter, D R

    2016-01-01

    The postsynaptic density (PSD) contains a complex set of proteins of known relevance to neuropsychiatric disorders such as schizophrenia and bipolar disorder. We enriched for this anatomical structure in the anterior cingulate cortex of 16 bipolar disorder samples and 20 controls from the Stanley Medical Research Institute. Unbiased shotgun proteomics incorporating label-free quantitation was used to identify differentially expressed proteins. Quantitative investigation of the PSD identified 2033 proteins, among which 288 were found to be differentially expressed. Validation of expression changes of DNM1, DTNA, NDUFV2, SEPT11 and SSBP was performed by western blotting. Bioinformatics analysis of the differentially expressed proteins implicated metabolic pathways including mitochondrial function, the tricarboxylic acid cycle, oxidative phosphorylation, protein translation and calcium signaling. The data implicate PSD-associated proteins, and specifically mitochondrial function in bipolar disorder. They relate synaptic function in bipolar disorder and the energy pathways that underpin it. Overall, our findings add to a growing literature linking the PSD and mitochondrial function in psychiatric disorders generally, and suggest that mitochondrial function associated with the PSD is particularly important in bipolar disorder. PMID:27898073

  20. Career pathways for temporary workers: exploring heterogeneous mobility dynamics with sequence analysis.

    PubMed

    Fuller, Sylvia; Stecy-Hildebrandt, Natasha

    2015-03-01

    Because temporary jobs are time-delimited, their implications for workers' economic security depend not only on their current characteristics, but also their place in longer-term patterns of mobility. Past research has typically asked whether temporary jobs are a bridge to better employment or trap workers in ongoing insecurity, investigating this question by analyzing single transitions. We demonstrate that this approach is ill-suited to assessing the often more complex and turbulent employment patterns characteristic of temporary workers. Our analysis instead employs sequence methods to compare a representative sample of temporary workers' month-by-month mobility patterns through 8 potential (non)employment states over five years. We derive a typology of trajectories and describe their relative precariousness in relation to employment stability and wage and earnings levels and growth. While some of the pathways correspond quite closely to frameworks used by past research, others reveal new and important distinctions. Multinomial logit models reveal job, employer, and worker characteristics associated with different pathways. Age, gender, and type of temporary work stand out as important factors shaping subsequent mobility patterns.

  1. Transcriptomic and functional pathways analysis of ascorbate-induced cytotoxicity and resistance of Burkitt lymphoma.

    PubMed

    Pei, Zenglin; Zhang, Xuan; Ji, Chunxia; Liu, Song-Mei; Wang, Jin

    2016-09-27

    Ascorbate is a pro-oxidant that generates hydrogen peroxide-dependent cytotoxity in cancer cells without adversely affecting normal cells. To determine the mechanistic basis for this phenotype, we selected Burkitt lymphoma cells resistant to ascorbate (JLPR cells) and their ascorbate-sensitive parental cells (JLPS cells). Compared with JLPS cells, the increased glucose uptake in JLPR cells (with upregulated glucose transporters, increased antioxidant enzyme activity, and altered cell cycling) conferred ascorbate-induced cytotoxicity and resistance. Transcriptomic profiles and function pathway analysis identified differentially expressed gene signatures for JLPR cells and JLPS cells, which differential expression levels of five genes (ATF5, CD79B, MHC, Myosin, and SAP18) in ascorbate-resistant cells were related to phosphoinositide 3 kinase, cdc42, DNA methylation and transcriptional repression, polyamine regulation, and integrin-linked kinase signaling pathways. These results suggested that coordinated changes occurred in JLPR cells to enable their survival when exposed to the cytotoxic pro-oxidant stress elicited by pharmacologic ascorbate treatment.

  2. Transcriptomic and functional pathways analysis of ascorbate-induced cytotoxicity and resistance of Burkitt lymphoma

    PubMed Central

    Ji, Chunxia; Liu, Song-Mei; Wang, Jin

    2016-01-01

    Ascorbate is a pro-oxidant that generates hydrogen peroxide–dependent cytotoxity in cancer cells without adversely affecting normal cells. To determine the mechanistic basis for this phenotype, we selected Burkitt lymphoma cells resistant to ascorbate (JLPR cells) and their ascorbate-sensitive parental cells (JLPS cells). Compared with JLPS cells, the increased glucose uptake in JLPR cells (with upregulated glucose transporters, increased antioxidant enzyme activity, and altered cell cycling) conferred ascorbate–induced cytotoxicity and resistance. Transcriptomic profiles and function pathway analysis identified differentially expressed gene signatures for JLPR cells and JLPS cells, which differential expression levels of five genes (ATF5, CD79B, MHC, Myosin, and SAP18) in ascorbate-resistant cells were related to phosphoinositide 3 kinase, cdc42, DNA methylation and transcriptional repression, polyamine regulation, and integrin-linked kinase signaling pathways. These results suggested that coordinated changes occurred in JLPR cells to enable their survival when exposed to the cytotoxic pro-oxidant stress elicited by pharmacologic ascorbate treatment. PMID:27590508

  3. Nanosystem Self-Assembly Pathways Discovered via All-Atom Multiscale Analysis

    PubMed Central

    Pankavich, Stephen D.; Ortoleva, Peter J.

    2012-01-01

    We consider the self-assembly of composite structures from a group of nanocomponents, each consisting of particles within an N-atom system. Self-assembly pathways and rates for nanocomposites are derived via a multiscale analysis of the classical Liouville equation. From a reduced statistical framework, rigorous stochastic equations for population levels of beginning, intermediate, and final aggregates are also derived. It is shown that the definition of an assembly type is a self-consistency criterion that must strike a balance between precision and the need for population levels to be slowly varying relative to the timescale of atomic motion. The deductive multiscale approach is complemented by a qualitative notion of multicomponent association and the ensemble of exact atomic-level configurations consistent with them. In processes such as viral self-assembly from proteins and RNA or DNA, there are many possible intermediates so that it is usually difficult to predict the most efficient assembly pathway. However, in the current study rates of assembly of each possible intermediate can be predicted. This avoids the need, as in a phenomenological approach, for recalibration with each new application. The method accounts for the feedback across scales in space and time that is fundamental to nanosystem self-assembly. The theory has applications to bionanostructures, geomaterials, engineered composites, and nanocapsule therapeutic delivery systems. PMID:22372746

  4. Analysis of circadian pattern reveals tissue-specific alternative transcription in leptin signaling pathway

    PubMed Central

    Ptitsyn, Andrey A; Gimble, Jeffrey M

    2007-01-01

    Background It has been previously reported that most mammalian genes display a circadian oscillation in their baseline expression. Consequently, the phase and amplitude of each component of a signal transduction cascade has downstream consequences. Results Here, we report our analysis of alternative transcripts in the leptin signaling pathway which is responsible for the systemic regulation of macronutrient storage and energy balance. We focused on the circadian expression pattern of a critical component of the leptin signaling system, suppressor of cytokine signaling 3 (SOCS3). On an Affymetrix GeneChip 430A2 microarray, this gene is represented by three probe sets targeting different regions within the 3' end of the last exon. We demonstrate that in murine brown adipose tissue two downstream 3' probe sets experience circadian baseline oscillation in counter-phase to the upstream probe set. Such differences in expression patterns are a telltale sign of alternative splicing within the last exon of SOCS3. In contrast, all three probe sets oscillated in a common phase in murine liver and white adipose tissue. This suggests that the regulation of SOCS3 expression in brown fat is tissue specific. Another component of the signaling pathway, Janus kinase (JAK), is directly regulated by SOCS and has alternative transcript probe sets oscillating in counter-phase in a white adipose tissue specific manner. Conclusion We hypothesize that differential oscillation of alternative transcripts may provide a mechanism to maintain steady levels of expression in spite of circadian baseline variation. PMID:18047714

  5. Enhancement of cordyceps polysaccharide production via biosynthetic pathway analysis in Hirsutella sinensis.

    PubMed

    Lin, Shan; Liu, Zhi-Qiang; Baker, Peter James; Yi, Ming; Wu, Hui; Xu, Feng; Teng, Yi; Zheng, Yu-Guo

    2016-11-01

    The addition of various sulfates for enhanced cordyceps polysaccharide (CP) production in submerged cultivation of H. sinensis was investigated, and manganese sulfate was found the most effective. 2mM of manganese sulfate on 0day (d) was investigated as the optimal adding condition, and the CP production reached optimum with 5.33%, increasing by 93.3% compared with the control. Furthermore, the consumption of three main precursors of CP was studied over cultivation under two conditions. Intracellular mannose content decreased by 43.1% throughout 6days cultivation, which corresponded to CP accumulation rate sharply increased from 0 d to 6 d, and mannose was considered as the most preferred precursor for generating CP. Subsequently, mannose biosynthetic pathway was constructed and verified for the first time in H. sinensis, which constituted the important part of CP biosynthesis, and transcriptional levels of the biosynthetic genes were studied. Transcriptional level of gene cpsA was significantly up-regulated 5.35-fold and it was a key gene involved both in mannose and CP biosynthesis. This study demonstrated that manganese sulfate addition is an efficient and simple way to improve CP production. Transcriptional analysis based on biosynthetic pathway was helpful to find key genes and better understand CP biosynthesis.

  6. LC-high-resolution multiple stage spectrometric analysis of diuretic compounds Unusual mass fragmentation pathways.

    PubMed

    Giancotti, Valeria; Medana, Claudio; Aigotti, Riccardo; Pazzi, Marco; Baiocchi, Claudio

    2008-09-29

    The analysis of diuretic compounds has become of great concern because of their extensive use both in therapy and in illicit treatments (such as masking agents in sport doping and drug abuse). The variety of chemical structures of this class of drugs encouraged the development of new methods and techniques of analysis, especially as regards to acidic compounds. LC/MS has so grown to be the reference technique for this kind of analysis in forensic and anti-doping confirmation purposes. Multiple stage MS permits identification of single drugs with high selectivity, but some unexpected pathways could weaken the entire process. In this work we aim to explain some unusual fragmentation steps using high-resolution MSn. For example, in the case of amiloride an intense product ion in MS3 analysis generates an apparent loss of 10Da. Water adduct formation and successive carbon monoxide elimination can explain this uncommon behavior, which was studied using different ion traps. Bendroflumethiazide MSn spectra show instead three successive HF losses, in spite of the presence of a radical site in the parent structure. Homolytic cleavages with radical ion production occur also in the case of protonated positive ion of ethacrynic acid (loss of chlorine radical) showing that such fragmentation behavior is not so rare as generally reported. Different ionization modes were studied and a tentative correlation with acidic-base properties was done. Multiple stage high-resolution mass spectra of positive and negative ions were discussed.

  7. Pathway analysis of Pichia pastoris to elucidate methanol metabolism and its regulation for production of recombinant proteins.

    PubMed

    Unrean, Pornkamol

    2014-01-01

    This research rationally analyzes metabolic pathways of Pichia pastoris to study the metabolic flux responses of this yeast under methanol metabolism. A metabolic model of P. pastoris was constructed and analyzed by elementary mode analysis (EMA). EMA was used to comprehensively identify the cell's metabolic flux profiles and its underlying regulation mechanisms for the production of recombinant proteins from methanol. Change in phenotypes and flux profiles during methanol adaptation with varying feed mixture of glycerol and methanol was examined. EMA identified increasing and decreasing fluxes during the glycerol-methanol metabolic shift, which well agreed with experimental observations supporting the validity of the metabolic network model. Analysis of all the identified pathways also led to the determination of the metabolic capacities as well as the optimum metabolic pathways for recombinant protein synthesis during methanol induction. The network sensitivity analysis revealed that the production of proteins can be improved by manipulating the flux ratios at the pyruvate branch point. In addition, EMA suggested that protein synthesis is optimum under hypoxic culture conditions. The metabolic modeling and analysis presented in this study could potentially form a valuable knowledge base for future research on rational design and optimization of P. pastoris by determining target genes, pathways, and culture conditions for enhanced recombinant protein synthesis. The metabolic pathway analysis is also of considerable value for production of therapeutic proteins by P. pastoris in biopharmaceutical applications.

  8. Inference of miRNA targets using evolutionary conservation and pathway analysis

    PubMed Central

    Gaidatzis, Dimos; van Nimwegen, Erik; Hausser, Jean; Zavolan, Mihaela

    2007-01-01

    probability to each putative target site. The results presented here indicate that our general method achieves very good performance in predicting miRNA target sites, providing at the same time insights into the evolution of target sites for individual miRNAs. Moreover, by combining our predictions with pathway analysis, we propose functions of specific miRNAs in nervous system development, inter-cellular communication and cell growth. The complete target site predictions as well as the miRNA/pathway associations are accessible on the ElMMo web server. PMID:17331257

  9. Use of Whatman-41 filters in air quality sampling networks (with applications to elemental analysis)

    NASA Technical Reports Server (NTRS)

    Neustadter, H. E.; Sidik, S. M.; King, R. B.; Fordyce, J. S.; Burr, J. C.

    1974-01-01

    The operation of a 16-site parallel high volume air sampling network with glass fiber filters on one unit and Whatman-41 filters on the other is reported. The network data and data from several other experiments indicate that (1) Sampler-to-sampler and filter-to-filter variabilities are small; (2) hygroscopic affinity of Whatman-41 filters need not introduce errors; and (3) suspended particulate samples from glass fiber filters averaged slightly, but not statistically significantly, higher than from Whatman-41-filters. The results obtained demonstrate the practicability of Whatman-41 filters for air quality monitoring and elemental analysis.

  10. CAESCAP: A computer code for compressed-air energy-storage-plant cycle analysis

    NASA Astrophysics Data System (ADS)

    Fort, J. A.

    1982-10-01

    The analysis code, CAESCAP, was developed as an aid in comparing and evaluating proposed compressed air energy storage (CAES) cycles. Input consists of component parameters and working fluid conditions at points along a cycle. The code calculates thermodynamic properties at each point and then calculates overall cycle performance. Working fluid capabilities include steam, air, nitrogen, and parahydrogen. The CAESCAP code was used to analyze a variety of CAES cycles. The combination of straightforward input and flexible design make the code easy and inexpensive to use.

  11. Well-to-wake analysis of ethanol-to-jet and sugar-to-jet pathways

    DOE PAGES

    Han, Jeongwoo; Tao, Ling; Wang, Michael

    2017-01-24

    To reduce the environmental impacts of the aviation sector as air traffic grows steadily, the aviation industry has paid increasing attention to bio-based alternative jet fuels (AJFs), which may provide lower life-cycle petroleum consumption and greenhouse gas (GHG) emissions than petroleum jet fuel. Here, this study presents well-to-wake (WTWa) results for four emerging AJFs: ethanol-to-jet (ETJ) from corn and corn stover, and sugar-to-jet (STJ) from corn stover via both biological and catalytic conversion. For the ETJ pathways, two plant designs were examined: integrated (processing corn or corn stover as feedstock) and distributed (processing ethanol as feedstock). Also, three H2 optionsmore » for STJ via catalytic conversion are investigated: external H2 from natural gas (NG) steam methane reforming (SMR), in situ H2, and H2 from biomass gasification. Results demonstrate that the feedstock is a key factor in the WTWa GHG emissions of ETJ: corn- and corn stover-based ETJ are estimated to produce WTWa GHG emissions that are 16 and 73%, respectively, less than those of petroleum jet. As for the STJ pathways, this study shows that STJ via biological conversion could generate WTWa GHG emissions 59% below those of petroleum jet. STJ via catalytic conversion could reduce the WTWa GHG emissions by 28% with H2 from NG SMR or 71% with H2 from biomass gasification than those of petroleum jet. This study also examines the impacts of co-product handling methods, and shows that the WTWa GHG emissions of corn stover-based ETJ, when estimated with a displacement method, are lower by 11 g CO2e/MJ than those estimated with an energy allocation method. Corn- and corn stover-based ETJ as well as corn stover-based STJ show potentials to reduce WTWa GHG emissions compared to petroleum jet. Particularly, WTWa GHG emissions of STJ via catalytic conversion depend highly on the hydrogen source. On the other hand, ETJ offers unique opportunities to exploit extensive existing corn

  12. Uncertainty Analysis of Air Radiation for Lunar Return Shock Layers

    NASA Technical Reports Server (NTRS)

    Kleb, Bil; Johnston, Christopher O.

    2008-01-01

    By leveraging a new uncertainty markup technique, two risk analysis methods are used to compute the uncertainty of lunar-return shock layer radiation predicted by the High temperature Aerothermodynamic Radiation Algorithm (HARA). The effects of epistemic uncertainty, or uncertainty due to a lack of knowledge, is considered for the following modeling parameters: atomic line oscillator strengths, atomic line Stark broadening widths, atomic photoionization cross sections, negative ion photodetachment cross sections, molecular bands oscillator strengths, and electron impact excitation rates. First, a simplified shock layer problem consisting of two constant-property equilibrium layers is considered. The results of this simplified problem show that the atomic nitrogen oscillator strengths and Stark broadening widths in both the vacuum ultraviolet and infrared spectral regions, along with the negative ion continuum, are the dominant uncertainty contributors. Next, three variable property stagnation-line shock layer cases are analyzed: a typical lunar return case and two Fire II cases. For the near-equilibrium lunar return and Fire 1643-second cases, the resulting uncertainties are very similar to the simplified case. Conversely, the relatively nonequilibrium 1636-second case shows significantly larger influence from electron impact excitation rates of both atoms and molecules. For all cases, the total uncertainty in radiative heat flux to the wall due to epistemic uncertainty in modeling parameters is 30% as opposed to the erroneously-small uncertainty levels (plus or minus 6%) found when treating model parameter uncertainties as aleatory (due to chance) instead of epistemic (due to lack of knowledge).

  13. Integrated miRNA–risk gene–pathway pair network analysis provides prognostic biomarkers for gastric cancer

    PubMed Central

    Cai, Hui; Xu, Jiping; Han, Yifang; Lu, Zhengmao; Han, Ting; Ding, Yibo; Ma, Liye

    2016-01-01

    Purpose This study aimed to identify molecular prognostic biomarkers for gastric cancer. Methods mRNA and miRNA expression profiles of eligible gastric cancer and control samples were downloaded from Gene Expression Omnibus to screen the differentially expressed genes (DEGs) and differentially expressed miRNAs (DEmiRs), using MetaDE and limma packages, respectively. Target genes of the DEmiRs were also collected from both predictive and experimentally validated target databases of miRNAs. The overlapping genes between selected targets and DEGs were identified as risk genes, followed by functional enrichment analysis. Human pathways and their corresponding genes were downloaded from the Kyoto Encyclopedia of Genes and Genomes (KEGG) database for the expression analysis of each pathway in gastric cancer samples. Next, co-pathway pairs were selected according to the Pearson correlation coefficients. Finally, the co-pathway pairs, miRNA–target pairs, and risk gene–pathway pairs were merged into a complex interaction network, the most important nodes (miRNAs/target genes/co-pathway pairs) of which were selected by calculating their degrees. Results Totally, 1,260 DEGs and 144 DEmiRs were identified. There were 336 risk genes found in the 9,572 miRNA–target pairs. Judging from the pathway expression files, 45 co-pathway pairs were screened out. There were 1,389 interactive pairs and 480 nodes in the integrated network. Among all nodes in the network, focal adhesion/extracellular matrix–receptor interaction pathways, CALM2, miR-19b, and miR-181b were the hub nodes with higher degrees. Conclusion CALM2, hsa-miR-19b, and hsa-miR-181b might be used as potential prognostic targets for gastric cancer. PMID:27284247

  14. Altered neural signaling and immune pathways in peripheral blood mononuclear cells of schizophrenia patients with cognitive impairment: A transcriptome analysis.

    PubMed

    Wu, Jing Qin; Green, Melissa J; Gardiner, Erin J; Tooney, Paul A; Scott, Rodney J; Carr, Vaughan J; Cairns, Murray J

    2016-03-01

    Cognitive deficits are a core feature of schizophrenia and contribute significantly to functional disability. We investigated the molecular pathways associated with schizophrenia (SZ; n=47) cases representing both 'cognitive deficit' (CD; n=22) and 'cognitively spared' (CS; n=25) subtypes of schizophrenia (based on latent class analysis of 9 cognitive performance indicators), compared with 49 healthy controls displaying 'normal' cognition. This was accomplished using gene-set analysis of transcriptome data derived from peripheral blood mononuclear cells (PBMCs). We detected 27 significantly altered pathways (19 pathways up-regulated and 8 down-regulated) in the combined SZ group and a further 6 pathways up-regulated in the CS group and 5 altered pathways (4 down-regulated and 1 up-regulated) in the CD group. The transcriptome profiling in SZ and cognitive subtypes were characterized by the up-regulated pathways involved in immune dysfunction (e.g., antigen presentation in SZ), energy metabolism (e.g., oxidative phosphorylation), and down-regulation of the pathways involved in neuronal signaling (e.g., WNT in SZ/CD and ERBB in SZ). When we looked for pathways that differentiated the two cognitive subtypes we found that the WNT signaling was significantly down-regulated (FDR<0.05) in the CD group in accordance with the combined SZ cohort, whereas it was unaffected in the CS group. This suggested suppression of WNT signaling was a defining feature of cognitive decline in schizophrenia. The WNT pathway plays a role in both the development/function of the central nervous system and peripheral tissues, therefore its alteration in PBMCs may be indicative of an important genomic axis relevant to cognition in the neuropathology of schizophrenia.

  15. Expression analysis of cytosolic DNA-sensing pathway genes in the intestinal mucosal layer of necrotic enteritis-induced chicken.

    PubMed

    Rengaraj, Deivendran; Truong, Anh Duc; Lee, Sung-Hyen; Lillehoj, Hyun S; Hong, Yeong Ho

    2016-02-01

    Necrotic enteritis (NE) is a serious problem to the poultry farms, which report NE outbreaks more than once per year, as a result of the inappropriate use of antibiotics in the feed. The NE affected bird die rapidly as a result of various pathophysiological complications in the intestine and immune system. Also, several studies have reported that the genes exclusively related to intestine and immune functions are significantly altered in response to NE. In this study, NE was induced in two genetically disparate chicken lines that are resistant (line 6.3) and sensitive (line 7.2) to avian leukosis and Marek's disease. The intestinal mucosal layer was collected from NE-induced and control chickens, and subjected to RNA-sequencing analysis. The involvement of differentially expressed genes in the intestinal mucosal layer of line 6.3 and 7.2 with the immune system-related pathways was investigated. Among the identified immune system-related pathways, a candidate pathway known as chicken cytosolic DNA-sensing pathway (CDS pathway) was selected for further investigation. RNA-sequencing and pathway analysis identified a total of 21 genes that were involved in CDS pathway and differentially expressed in the intestinal mucosal layer of lines 6.3 and 7.2. The expression of CDS pathway genes was further confirmed by real-time qPCR. In the results, a majority of the CDS pathway genes were significantly altered in the NE-induced intestinal mucosal layer from lines 6.3 and 7.2. In conclusion, our study indicate that NE seriously affects several genes involved in innate immune defense and foreign DNA sensing mechanisms in the chicken intestinal mucosal layer. Identifying the immune genes affected by NE could be an important evidence for the protective immune response to NE-causative pathogens.

  16. Integrating pathway analysis and genetics of gene expression for genome-wide association study of basal cell carcinoma.

    PubMed

    Zhang, Mingfeng; Liang, Liming; Morar, Nilesh; Dixon, Anna L; Lathrop, G Mark; Ding, Jun; Moffatt, Miriam F; Cookson, William O C; Kraft, Peter; Qureshi, Abrar A; Han, Jiali

    2012-04-01

    Genome-wide association studies (GWASs) have primarily focused on marginal effects for individual markers and have incorporated external functional information only after identifying robust statistical associations. We applied a new approach combining the genetics of gene expression and functional classification of genes to the GWAS of basal cell carcinoma (BCC) to identify potential biological pathways associated with BCC. We first identified 322,324 expression-associated single-nucleotide polymorphisms (eSNPs) from two existing GWASs of global gene expression in lymphoblastoid cell lines (n = 955), and evaluated the association of these functionally annotated SNPs with BCC among 2,045 BCC cases and 6,013 controls in Caucasians. We then grouped them into 99 KEGG pathways for pathway analysis and identified two pathways associated with BCC with p value <0.05 and false discovery rate (FDR) <0.5: the autoimmune thyroid disease pathway (mainly HLA class I and II antigens, p < 0.001, FDR = 0.24) and Janus kinase-signal transducer and activator of transcription (JAK-STAT) signaling pathway (p = 0.02, FDR = 0.49). Seventy-nine (25.7%) out of 307 significant eSNPs in the JAK-STAT pathway were associated with BCC risk (p < 0.05) in an independent replication set of 278 BCC cases and 1,262 controls. In addition, the association of JAK-STAT signaling pathway was marginally validated using 16,691 eSNPs identified from 110 normal skin samples (p = 0.08). Based on the evidence of biological functions of the JAK-STAT pathway on oncogenesis, it is plausible that this pathway is involved in BCC pathogenesis.

  17. Evaluation of tetraglyme for the enrichment and analysis of volatile organic compounds in air.

    PubMed

    Huybrechts, T; Dewulf, J; Van Craeynest, K; Van Langenhove, H

    2001-07-13

    A recently developed method for the sampling and analysis of volatile organic compounds in air has been evaluated. The system is based on the enrichment of analytes in tetraethylene glycol dimethyl ether or tetraglyme, a water-soluble organic liquid. The subsequent analysis consists of dispersion of a sample aliquot in water followed by purge-and-trap and gas chromatographic separation. Physico-chemical data were investigated for 10 volatile organic compounds, providing information on the possibilities and limitations of the tetraglyme method. The target analytes included chlorinated alkanes and alkenes, and monocyclic aromatic hydrocarbons. Air/tetraglyme partition coefficients Kat were determined over an environmental relevant temperature range of 2-25 degrees C to evaluate sorption efficiencies and estimate breakthrough volumes at the sampling stage. At 2 degrees C breakthrough volumes (allowing 5% of breakthrough) ranged from 5.8 (1,1-dichloroethane) to 312 l (1,1,2-trichloroethane) for 20 ml of tetraglyme. With regard to the desorption stage, the effect of tetraglyme on the air/water partition of organic compounds was investigated through the measurement of air/tetraglyme-water partition coefficients Kat-w for 2-31% (v/v) tetraglyme in water. Finally a clean-up procedure for tetraglyme was evaluated. Analysis of a blank tetraglyme-water (17:83, v:v) mixture by gas chromatography-flame ionization detection/mass spectrometry showed minor background signals. None of the target compounds were detected.

  18. Spatial Analysis of Air Quality Monitor Data in China, Japan, and South Korea

    NASA Astrophysics Data System (ADS)

    Rohde, Robert

    2016-04-01

    In 2015, Berkeley Earth published a widely-reported study concluding that air pollution contributes to 1.6 million deaths per year in China. This presentation will provide an update on that work with additional data for China and new analysis for South Korea and Japan. In China, two years of data from more than 1500 monitoring stations allows local trends to be estimated. Preliminary review indicates a trend towards improving air quality across most of China with decreasing emissions at most major population centers. Such improvements are consistent with tightening emissions standards and the decreasing usage of coal. In addition, new spatial analysis has been applied to ~900 monitoring sites in Japan and ~120 sites in South Korea. This new analysis provides information on air quality, pollutant source distributions, and implied mortality in these countries. Finally, boundary crossing fluxes in South Korea and Japan have been used to estimate the fraction of air pollution in Japan and South Korea that has being imported from sources in China.

  19. Federal Air Pollutant Emission Regulations and Preliminary Estimates of Potential-to-Emit from Biorefineries, Pathway #2: Conversion of Lignocellulosic Biomass to Hydrocarbon Fuels: Fast Pyrolysis and Hydrotreating Bio-oil Pathway

    SciTech Connect

    Bhatt, Arpit; Zhang, Yimin; Heath, Garvin; Thomas, Mae; Renzaglia, Jason

    2017-01-01

    Biorefineries are subject to environmental laws, including complex air quality regulations that aim to protect and improve the quality of the air. These regulations govern the amount of certain types of air pollutants that can be emitted from different types of emission sources. To determine which federal air emission regulations potentially apply to the fast pyrolysis biorefinery, we first identified the types of regulated air pollutants emitted to the ambient environment by the biorefinery or from specific equipment. Once the regulated air pollutants are identified, we review the applicability criteria of each federal air regulation to determine whether the fast pyrolysis biorefinery or specific equipment is subject to it. We then estimate the potential-to-emit of pollutants likely to be emitted from the fast pyrolysis biorefinery to understand the air permitting requirements.

  20. The Sky is Falling: An air deposition/stormwater runoff model simulating the pathways of five heavy metals from their status as mobile and stack exhaust constituents to their delivery to the Elizabeth River

    SciTech Connect

    Barrett-McDaniels, J.; Barrett, M.

    1997-12-31

    Recent studies by the Environmental Protection Agency (EPA) indicate that air emissions contribute a major portion of the total loading of toxic metals to the waters of the Chesapeake Bay and its tributaries. According to the Chesapeake Executive Council of the interstate Chesapeake Bay Program, five of these metals, cadmium, chromium, copper, lead, and zinc, have been observed to have a negative impact on the waters of the Elizabeth River, which is within the Chesapeake Bay watershed. In order to better define the sources and processes which contribute to concentrations of these metals in the Elizabeth River, this analysis simulates the pathway of these metals from their status as mobile and stack exhaust constituents to their delivery to the river. EPA`s ISCST3 model was used to predict deposition loading on the Elizabeth River water and watershed surfaces, using regional annual meteorological data. Air emissions input to the ISCST3 model were derived from stationary and mobile sources: stationary source emissions were estimated using Virginia Department of Environmental Quality inventories and EPA-approved emissions factors for major sources with the potential to impact the watershed, while mobile source emissions were estimated using traffic volumes provided by the Department of Transportation and EPA-approved emissions factors. EPA`s SWMM model was then used to predict maximum short term and average annual build up and wash off rates for these metals using recorded rainfall data and existing land use and impervious cover for the watershed. The results are compared to water quality monitoring data from the municipal NPDES stormwater wet weather monitoring permit program.

  1. Pharmacological analysis of feeding in a caterpillar: different transduction pathways for umami and saccharin?

    NASA Astrophysics Data System (ADS)

    Pszczolkowski, Maciej A.; Durden, Kevin; Marquis, Juleah; Ramaswamy, Sonny B.; Brown, John J.

    2009-05-01

    Neonate larvae of codling moth, Cydia pomonella (L.), modify their behavior in the presence of saccharin, monosodium glutamate (MSG), or L(+)-2-amino-4-phosphonobutyric acid (L-AP4) by commencing their feeding earlier. Previously published pharmacological analysis demonstrated that phagostimulatory effects of MSG and L-AP4 (which elicit umami taste sensation in humans) are reversed by adenylate cyclase activator and phosphodiesterase inhibitor. In this study, by measuring the time needed to start ingestion of foliage treated with mixtures of phagostimulants and signal transduction modulators, we show that phagostimulatory effects of l-aspartate (the third hallmark umami substance) are also abolished by both adenylate cyclase activator and phosphodiesterase inhibitor, but not by phospholipase C inhibitor. However, stimulatory effects of hemicalcium saccharin were affected only by phospholipase C inhibitor. The results suggest that codling moth neonates use different transduction pathways for perception of hemicalcium saccharin and umami.

  2. Analysis of molecular oxygen exit pathways in cyanobacterial photosystem II: Molecular dynamics studies

    NASA Astrophysics Data System (ADS)

    Gabdulkhakov, A. G.; Kljashtorny, V. G.; Dontsova, M. V.

    2015-11-01

    In thylakoids of cyanobacteria and other photosynthetic organisms, the light-induced production of molecular oxygen is catalyzed by the giant lipid-pigment-protein complex called photosystem II (PSII). The oxygen-evolving complex is buried deep in the lumenal part of PSII, and dioxygen molecules need to pass through the protein environment in order to leave the active site of the enzyme free. Previous studies aimed at finding oxygen channels in PSII were based on either an analysis of the cavities within is static structure or experiments on the insertion of noble gas molecules into PSII crystals under elevated pressure. In these studies, some possible exit pathways for the molecules were found and the static positions of molecular oxygen were determined. In the present work, the oxygen movement in the transport system of PSII is simulated by molecular dynamics.

  3. Retracted: Identification of Novel Biomarkers for Pancreatic Cancer Using Integrated Transcriptomics With Functional Pathways Analysis.

    PubMed

    Zhang, Xuan; Tong, Pan; Chen, Jinyun; Pei, Zenglin; Zhang, Xiaoyan; Chen, Weiping; Xu, Jianqing; Wang, Jin

    2016-02-22

    Retraction: 'Identification of Novel Biomarkers for Pancreatic Cancer Using Integrated Transcriptomics With Functional Pathways Analysis' by Zhang, X., Tong, P., Chen, J., Pei, Z., Zhang, X., Chen, W., Xu, J. and Wang, J. The above article from the Journal of Cellular Physiology, published online on 10 March 2016 in Wiley Online Library as Early View (http://onlinelibrary.wiley.com/enhanced/doi/10.1002/jcp.25353/), has been retracted by agreement between Gary Stein, the journal's Editor-in-Chief, and Wiley Periodicals, Inc. The retraction has been agreed following an investigation at the University of Texas, MD Anderson Cancer Center, which confirmed that the article was submitted and approved for publication by Dr. Jin Wang without acknowledgement of NIH funding received or the consent and authorship of Dr. Ann Killary and Dr. Subrata Sen, with whom the manuscript was originally drafted.

  4. Identifying host pathogenic pathways in bovine digital dermatitis by RNA-Seq analysis.

    PubMed

    Scholey, R A; Evans, N J; Blowey, R W; Massey, J P; Murray, R D; Smith, R F; Ollier, W E; Carter, S D

    2013-09-01

    Digital dermatitis is a painful foot disease compromising welfare in dairy cattle. The disease has a complex multibacterial aetiology, but little is known about its pathogenesis. In this study, gene expression in skin biopsies from five bovine digital dermatitis lesions and five healthy bovine feet was compared using RNA-Seq technology. Differential gene expression was determined after mapping transcripts to the Btau 4.0 genome. Pathway analysis identified gene networks involving differentially expressed transcripts. Bovine digital dermatitis lesions had increased expression of mRNA for α2-macroglobulin-like 1, a protein potentially involved in bacterial immune evasion and bacterial survival. There was increased expression of keratin 6A and interleukin 1β mRNA in bovine digital dermatitis lesions, but reduced expression of most other keratin and keratin-associated genes. There was little evidence of local immune reactions to the bacterial infection present in lesions.

  5. Air Pollution.

    ERIC Educational Resources Information Center

    Gilpin, Alan

    A summary of one of our most pressing environmental problems, air pollution, is offered in this book by the Director of Air Pollution Control for the Queensland (Australia) State Government. Discussion of the subject is not restricted to Queensland or Australian problems and policies, however, but includes analysis of air pollution the world over.…

  6. Analysis of industrial contaminants in indoor air. Part 2. Emergent contaminants and pesticides.

    PubMed

    Garcia-Jares, Carmen; Regueiro, Jorge; Barro, Ruth; Dagnac, Thierry; Llompart, Maria

    2009-01-16

    This article reviews recent literature on the analysis of several contaminants related to the industrial development in indoor air in the framework of the REACH project. In this second part, the attention is focused on emergent contaminants and biocides. Among these chemicals, phthalates, polybrominated and phosphate flame retardants, fragrances, pesticides, as well as other emerging pollutants, are increasing their environmental and health concern and are extensively found in indoor air. Some of them are suspected to behave as priority organic pollutants (POPs) and/or endocrine disrupting compounds (EDC), and can be found both in air and associated to the suspended particulate matter (PM) and settled dust. Main literature considered for this review is from the last ten years, reporting analytical developments and applications regarding the considered contaminants in the indoor environment. Sample collection and pretreatment, analyte extraction or desorption, clean-up procedures, determination techniques, and performance results are summarized and discussed.

  7. Analysis of Bacterial Detachment from Substratum Surfaces by the Passage of Air-Liquid Interfaces

    PubMed Central

    Gómez-Suárez, Cristina; Busscher, Henk J.; van der Mei, Henny C.

    2001-01-01

    A theoretical analysis of the detachment of bacteria adhering to substratum surfaces upon the passage of an air-liquid interface is given, together with experimental results for bacterial detachment in the absence and presence of a conditioning film on different substratum surfaces. Bacteria (Streptococcus sobrinus HG1025, Streptococcus oralis J22, Actinomyces naeslundii T14V-J1, Bacteroides fragilis 793E, and Pseudomonas aeruginosa 974K) were first allowed to adhere to hydrophilic glass and hydrophobic dimethyldichlorosilane (DDS)-coated glass in a parallel-plate flow chamber until a density of 4 × 106 cells cm−2 was reached. For S. sobrinus HG1025, S. oralis J22, and A. naeslundii T14V-J1, the conditioning film consisted of adsorbed salivary components, while for B. fragilis 793E and P. aeruginosa 974K, the film consisted of adsorbed human plasma components. Subsequently, air bubbles were passed through the flow chamber and the bacterial detachment percentages were measured. For some experimental conditions, like with P. aeruginosa 974K adhering to DDS-coated glass and an air bubble moving at high velocity (i.e., 13.6 mm s−1), no bacteria detached upon passage of an air-liquid interface, while for others, detachment percentages between 80 and 90% were observed. The detachment percentage increased when the velocity of the passing air bubble decreased, regardless of the bacterial strain and substratum surface hydrophobicity involved. However, the variation in percentages of detachment by a passing air bubble depended greatly upon the strain and substratum surface involved. At low air bubble velocities the hydrophobicity of the substratum had no influence on the detachment, but at high air bubble velocities all bacterial strains were more efficiently detached from hydrophilic glass substrata. Furthermore, the presence of a conditioning film could either inhibit or stimulate detachment. The shape of the bacterial cell played a major role in detachment at high

  8. Exploratory Analysis of Spatial-Temporal Patterns of Air Pollution in the City

    NASA Astrophysics Data System (ADS)

    Champendal, Alexandre; Kanevski, Mikhail; Huguenot, Pierre-Emmanuel; Golay, Jean

    2013-04-01

    Air pollution in the city is an important problem influencing environment, well-being of society, economy, management of urban zones, etc. The problem is extremely difficult due to a very complex distribution of the pollution sources, morphology of the city and dispersion processes leading to multivariate nature of the phenomena and high local spatial-temporal variability. The task of understanding, modelling and prediction of spatial-temporal patterns of air pollution in urban zones is an interesting and challenging topic having many research axes from science-based modelling to geostatistics and data mining. The present research mainly deals with a comprehensive exploratory analysis of spatial-temporal air pollution data using statistical, geostatistical and machine learning tools. This analysis helps to 1) understand and model spatial-temporal correlations using variography, 2) explore the temporal evolution of spatial correlation matrix; 3) analyse and visualize an interconnection between measurement stations using network science tools; 4) quantify the availability and predictability of structured patterns. The real data case study deals with spatial-temporal air pollution data of canton Geneva (2002-2011). Carbon dioxide (NO2) have caught our attention. It has effects on health: nitrogen dioxide can irritate the lungs, effects on plants; NO2 contributes to the phenomenon of acid rain. The negative effects of nitrogen dioxides on plants are reducing the growth, production and pesticide resistance. And finally the effects on materials: nitrogen dioxides increase the corrosion. Well-defined patterns of spatial-temporal correlations were detected. The analysis and visualization of spatial correlation matrix for 91 stations were carried out using the network science tools and high levels of clustering were revealed. Moving Window Correlation Matrix and Spatio-temporal variography methods were applied to define and explore the dynamic of our data. More than just

  9. Robustness analysis of an air heating plant and control law by using polynomial chaos

    SciTech Connect

    Colón, Diego; Ferreira, Murillo A. S.; Bueno, Átila M.; Balthazar, José M.; Rosa, Suélia S. R. F. de

    2014-12-10

    This paper presents a robustness analysis of an air heating plant with a multivariable closed-loop control law by using the polynomial chaos methodology (MPC). The plant consists of a PVC tube with a fan in the air input (that forces the air through the tube) and a mass flux sensor in the output. A heating resistance warms the air as it flows inside the tube, and a thermo-couple sensor measures the air temperature. The plant has thus two inputs (the fan's rotation intensity and heat generated by the resistance, both measured in percent of the maximum value) and two outputs (air temperature and air mass flux, also in percent of the maximal value). The mathematical model is obtained by System Identification techniques. The mass flux sensor, which is nonlinear, is linearized and the delays in the transfer functions are properly approximated by non-minimum phase transfer functions. The resulting model is transformed to a state-space model, which is used for control design purposes. The multivariable robust control design techniques used is the LQG/LTR, and the controllers are validated in simulation software and in the real plant. Finally, the MPC is applied by considering some of the system's parameters as random variables (one at a time, and the system's stochastic differential equations are solved by expanding the solution (a stochastic process) in an orthogonal basis of polynomial functions of the basic random variables. This method transforms the stochastic equations in a set of deterministic differential equations, which can be solved by traditional numerical methods (That is the MPC). Statistical data for the system (like expected values and variances) are then calculated. The effects of randomness in the parameters are evaluated in the open-loop and closed-loop pole's positions.

  10. Analysis of major air pollutants and submicron particles in New York City and Long Island

    NASA Astrophysics Data System (ADS)

    Masiol, M.; Hopke, P. K.; Felton, H. D.; Frank, B. P.; Rattigan, O. V.; Wurth, M. J.; LaDuke, G. H.

    2017-01-01

    A year-long sampling campaign of major air pollu