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Sample records for air pathway analysis

  1. The Cardiopulmonary Effects of Ambient Air Pollution and Mechanistic Pathways: A Comparative Hierarchical Pathway Analysis

    PubMed Central

    Thomas, Duncan C.; Zhang, Junfeng; Kipen, Howard M.; Rich, David Q.; Zhu, Tong; Huang, Wei; Hu, Min; Wang, Guangfa; Wang, Yuedan; Zhu, Ping; Lu, Shou-En; Ohman-Strickland, Pamela; Diehl, Scott R.; Eckel, Sandrah P.

    2014-01-01

    Previous studies have investigated the associations between exposure to ambient air pollution and biomarkers of physiological pathways, yet little has been done on the comparison across biomarkers of different pathways to establish the temporal pattern of biological response. In the current study, we aim to compare the relative temporal patterns in responses of candidate pathways to different pollutants. Four biomarkers of pulmonary inflammation and oxidative stress, five biomarkers of systemic inflammation and oxidative stress, ten parameters of autonomic function, and three biomarkers of hemostasis were repeatedly measured in 125 young adults, along with daily concentrations of ambient CO, PM2.5, NO2, SO2, EC, OC, and sulfate, before, during, and after the Beijing Olympics. We used a two-stage modeling approach, including Stage I models to estimate the association between each biomarker and pollutant over each of 7 lags, and Stage II mixed-effect models to describe temporal patterns in the associations when grouping the biomarkers into the four physiological pathways. Our results show that candidate pathway groupings of biomarkers explained a significant amount of variation in the associations for each pollutant, and the temporal patterns of the biomarker-pollutant-lag associations varied across candidate pathways (p<0.0001) and were not linear (from lag 0 to lag 3: p = 0.0629, from lag 3 to lag 6: p = 0.0005). These findings suggest that, among this healthy young adult population, the pulmonary inflammation and oxidative stress pathway is the first to respond to ambient air pollution exposure (within 24 hours) and the hemostasis pathway responds gradually over a 2–3 day period. The initial pulmonary response may contribute to the more gradual systemic changes that likely ultimately involve the cardiovascular system. PMID:25502951

  2. SPECIAL ANALYSIS AIR PATHWAY MODELING OF E-AREA LOW-LEVEL WASTE FACILITY

    SciTech Connect

    Hiergesell, R.; Taylor, G.

    2011-08-30

    This Special Analysis (SA) was initiated to address a concern expressed by the Department of Energy's Low Level Waste Disposal Facility Federal Review Group (LFRG) Review Team during their review of the 2008 E-Area Performance Assessment (PA) (WSRC, 2008). Their concern was the potential for overlapping of atmospheric plumes, emanating from the soil surface above SRS LLW disposal facilities within the E-Area, to contribute to the dose received by a member of the public during the Institutional Control (IC) period. The implication of this concern was that the dose to the maximally-exposed individual (MEI) located at the SRS boundary might be underestimated during this time interval. To address this concern a re-analysis of the atmospheric pathway releases from E-Area was required. In the process of developing a new atmospheric release model (ARM) capable of addressing the LFRG plume overlap concern, it became obvious that new and better atmospheric pathway disposal limits should be developed for each of the E-Area disposal facilities using the new ARM. The scope of the SA was therefore expanded to include the generation of these new limits. The initial work conducted in this SA was to develop a new ARM using the GoldSim{reg_sign} program (GTG, 2009). The model simulates the subsurface vapor diffusion of volatile radionuclides as they release from E-Area disposal facility waste zones and migrate to the land surface. In the process of this work, many new features, including several new physical and chemical transport mechanisms, were incorporated into the model. One of the most important improvements was to incorporate a mechanism to partition volatile contaminants across the water-air interface within the partially saturated pore space of the engineered and natural materials through which vapor phase transport occurs. A second mechanism that was equally important was to incorporate a maximum concentration of 1.9E-07 Ci/m{sup 3} of {sup 14}CO{sub 2} in the air

  3. Air Research Program: Key Pathways research track

    EPA Science Inventory

    The pathways research track applies animal, cellular, and human studies to discern whether there is a common molecular mechanism (e.g. production of oxidative stress, phosphatase inhibition, disruption of iron homeostasis) through which air pollutants induce toxicity of air pollu...

  4. 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.

  5. Pathway analysis of coronary atherosclerosis.

    PubMed

    King, Jennifer Y; Ferrara, Rossella; Tabibiazar, Raymond; Spin, Joshua M; Chen, Mary M; Kuchinsky, Allan; Vailaya, Aditya; Kincaid, Robert; Tsalenko, Anya; Deng, David Xing-Fei; Connolly, Andrew; Zhang, Peng; Yang, Eugene; Watt, Clifton; Yakhini, Zohar; Ben-Dor, Amir; Adler, Annette; Bruhn, Laurakay; Tsao, Philip; Quertermous, Thomas; Ashley, Euan A

    2005-09-21

    Large-scale gene expression studies provide significant insight into genes differentially regulated in disease processes such as cancer. However, these investigations offer limited understanding of multisystem, multicellular diseases such as atherosclerosis. A systems biology approach that accounts for gene interactions, incorporates nontranscriptionally regulated genes, and integrates prior knowledge offers many advantages. We performed a comprehensive gene level assessment of coronary atherosclerosis using 51 coronary artery segments isolated from the explanted hearts of 22 cardiac transplant patients. After histological grading of vascular segments according to American Heart Association guidelines, isolated RNA was hybridized onto a customized 22-K oligonucleotide microarray, and significance analysis of microarrays and gene ontology analyses were performed to identify significant gene expression profiles. Our studies revealed that loss of differentiated smooth muscle cell gene expression is the primary expression signature of disease progression in atherosclerosis. Furthermore, we provide insight into the severe form of coronary artery disease associated with diabetes, reporting an overabundance of immune and inflammatory signals in diabetics. We present a novel approach to pathway development based on connectivity, determined by language parsing of the published literature, and ranking, determined by the significance of differentially regulated genes in the network. In doing this, we identify highly connected "nexus" genes that are attractive candidates for therapeutic targeting and followup studies. Our use of pathway techniques to study atherosclerosis as an integrated network of gene interactions expands on traditional microarray analysis methods and emphasizes the significant advantages of a systems-based approach to analyzing complex disease. PMID:15942018

  6. 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.

  7. 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…

  8. Pathway-Based Functional Analysis of Metagenomes

    NASA Astrophysics Data System (ADS)

    Bercovici, Sivan; Sharon, Itai; Pinter, Ron Y.; Shlomi, Tomer

    Metagenomic data enables the study of microbes and viruses through their DNA as retrieved directly from the environment in which they live. Functional analysis of metagenomes explores the abundance of gene families, pathways, and systems, rather than their taxonomy. Through such analysis researchers are able to identify those functional capabilities most important to organisms in the examined environment. Recently, a statistical framework for the functional analysis of metagenomes was described that focuses on gene families. Here we describe two pathway level computational models for functional analysis that take into account important, yet unaddressed issues such as pathway size, gene length and overlap in gene content among pathways. We test our models over carefully designed simulated data and propose novel approaches for performance evaluation. Our models significantly improve over current approach with respect to pathway ranking and the computations of relative abundance of pathways in environments.

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

    SciTech Connect

    Dixon, K; Mark Phifer, M

    2007-09-17

    The F-Area Tank Farm (FTF) is located within F-Area in the General Separations Area (GSA) of the Savannah River Site (SRS) as seen in Figure 1. The GSA contains the F and H Area Separations Facilities, the S-Area Defense Waste Processing Facility, the Z-Area Saltstone Facility, and the E-Area Low-Level Waste Disposal Facilities. The FTF is a nearly rectangular shaped area and comprises approximately 20 acres, which is bounded by SRS coordinates N 76,604.5 to N 77,560.0 and E 52,435.0 to E 53,369.0. SRS is in the process of preparing a Performance Assessment (PA) to support FTF closure. As part of the PA process, an analysis was conducted to evaluate the potential magnitude of gaseous release of radionuclides from the FTF over the 100-year institutional control period and 10,000-year post-closure compliance period. Specifically, an air and radon pathways analysis has been conducted 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. 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

  10. Subpathway Analysis based on Signaling-Pathway Impact Analysis of Signaling Pathway

    PubMed Central

    Li, Xianbin; Shen, Liangzhong; Shang, Xuequn; Liu, Wenbin

    2015-01-01

    Pathway analysis is a common approach to gain insight from biological experiments. Signaling-pathway impact analysis (SPIA) is one such method and combines both the classical enrichment analysis and the actual perturbation on a given pathway. Because this method focuses on a single pathway, its resolution generally is not very high because the differentially expressed genes may be enriched in a local region of the pathway. In the present work, to identify cancer-related pathways, we incorporated a recent subpathway analysis method into the SPIA method to form the “sub-SPIA method.” The original subpathway analysis uses the k-clique structure to define a subpathway. However, it is not sufficiently flexible to capture subpathways with complex structure and usually results in many overlapping subpathways. We therefore propose using the minimal-spanning-tree structure to find a subpathway. We apply this approach to colorectal cancer and lung cancer datasets, and our results show that sub-SPIA can identify many significant pathways associated with each specific cancer that other methods miss. Based on the entire pathway network in the Kyoto Encyclopedia of Genes and Genomes, we find that the pathways identified by sub-SPIA not only have the largest average degree, but also are more closely connected than those identified by other methods. This result suggests that the abnormality signal propagating through them might be responsible for the specific cancer or disease. PMID:26207919

  11. 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

  12. Pathway-based analysis of breast cancer

    PubMed Central

    Song, Dong; Cui, Miao; Zhao, Gang; Fan, Zhimin; Nolan, Katherine; Yang, Ying; Lee, Peng; Ye, Fei; Zhang, David Y

    2014-01-01

    Introduction: Although HER2 and ER pathways are predominant pathways altered in breast cancer, it is now well accepted that many other signaling pathways are also involved in the pathogenesis of breast cancer. The understanding of these additional pathways may assist in identifying new therapeutic approaches for breast cancer. Methods: 13 invasive ductal carcinoma tissues and 5 benign breast tissues were analyzed for the mRNA expression level of 1243 cancer pathway-related genes using SmartChip (WaferGen, CA), a real-time PCR-base method. In addition, the levels of 131 cancer pathway-related proteins and phosphoproteins in 33 paired breast cancers were measured using our innovative Protein Pathway Array. Results: Out of 1,243 mRNAs, 68.7% (854) were detected in breast cancer and 395 mRNAs were statistically significant (fold change >2) between benign and cancer tissues. Of these mRNAs, 105 only expressed in breast cancer tissues and 33 mRNAs only expressed in normal breast tissues. Out of 131 proteins and phosphoproteins, 68% (89) were detected in cancer tissues and 57 proteins were significantly differentiated between tumor and normal tissues. Interestingly, only 3 genes (CDK6, Vimentin and SLUG) showed decreases in both protein and mRNA. Six proteins (BCL6, CCNE1, PCNA, PDK1, SRC and XIAP) were differentially expressed between tumor and normal tissues but no differences were observed at mRNA levels. Analyses of mRNA and protein data using Ingenuity Pathway Analysis showed more than 15 pathways were altered in breast cancer and 6 of which were shared between mRNAs and proteins, including p53, IL17, HGF, NGF, PTEN and PI3K/AKT pathways. Conclusions: There is a broad dysregulation of various pathways in breast cancer both at protein levels and mRNA levels. It is important to note that mRNA expression does not correlate with protein level, suggesting different regulation mechanisms between proteins and mRNAs. PMID:24936222

  13. Pathway and network analysis of cancer genomes.

    PubMed

    2015-07-01

    Genomic information on tumors from 50 cancer types cataloged by the International Cancer Genome Consortium (ICGC) shows that only a few well-studied driver genes are frequently mutated, in contrast to many infrequently mutated genes that may also contribute to tumor biology. Hence there has been large interest in developing pathway and network analysis methods that group genes and illuminate the processes involved. We provide an overview of these analysis techniques and show where they guide mechanistic and translational investigations. PMID:26125594

  14. Pathway and Network Analysis of Cancer Genomes

    PubMed Central

    Haider, Syed; Wu, Guanming; Shibata, Tatsuhiro; Vazquez, Miguel; Mustonen, Ville; Gonzalez-Perez, Abel; Pearson, John; Sander, Chris; Raphael, Benjamin J.; Marks, Debora S.; Ouellette, B.F. Francis; Valencia, Alfonso; Bader, Gary D.; Boutros, Paul C.; Stuart, Joshua M.; Linding, Rune; Lopez-Bigas, Nuria; Stein, Lincoln D.

    2016-01-01

    Genomic information on tumors from 50 cancer types catalogued by The International Cancer Genome Consortium (ICGC) shows that only few well-studied driver genes are frequently mutated, in contrast to many infrequently mutated genes that may also contribute to tumor biology. Hence there has been large interest in developing pathway and network analysis methods that group genes and illuminate the processes involved. We provide an overview of these analysis techniques and show where they guide mechanistic and translational investigations. PMID:26125594

  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. Pathway Analysis Software: Annotation Errors and Solutions

    PubMed Central

    Henderson-MacLennan, Nicole K.; Papp, Jeanette C.; Talbot, C. Conover; McCabe, Edward R.B.; Presson, Angela P.

    2010-01-01

    Genetic databases contain a variety of annotation errors that often go unnoticed due to the large size of modern genetic data sets. Interpretation of these data sets requires bioinformatics tools that may contribute to this problem. While providing gene symbol annotations for identifiers (IDs) such as microarray probeset, RefSeq, GenBank and Entrez Gene is seemingly trivial, the accuracy is fundamental to any subsequent conclusions. We examine gene symbol annotations and results from three commercial pathway analysis software (PAS) packages: Ingenuity Pathways Analysis, GeneGO and Pathway Studio. We compare gene symbol annotations and canonical pathway results over time and among different input ID types. We find that PAS results can be affected by variation in gene symbol annotations across software releases and the input ID type analyzed. As a result, we offer suggestions for using commercial PAS and reporting microarray results to improve research quality. We propose a wiki type website to facilitate communication of bioinformatics software problems within the scientific community. PMID:20663702

  17. Large scale air monitoring: lichen vs. air particulate matter analysis.

    PubMed

    Rossbach, M; Jayasekera, R; Kniewald, G; Thang, N H

    1999-07-15

    Biological indicator organisms have been widely used for monitoring and banking purposes for many years. Although the complexity of the interactions between organisms and their environment is generally not easily comprehensible, environmental quality assessment using the bioindicator approach offers some convincing advantages compared to direct analysis of soil, water, or air. Measurement of air particulates is restricted to experienced laboratories with access to expensive sampling equipment. Additionally, the amount of material collected generally is just enough for one determination per sampling and no multidimensional characterization might be possible. Further, fluctuations in air masses have a pronounced effect on the results from air filter sampling. Combining the integrating property of bioindicators with the world wide availability and particular matrix characteristics of air particulate matter as a prerequisite for global monitoring of air pollution is discussed. A new approach for sampling urban dust using large volume filtering devices installed in air conditioners of large hotel buildings is assessed. A first experiment was initiated to collect air particulates (300-500 g each) from a number of hotels during a period of 3-4 months by successive vacuum cleaning of used inlet filters from high volume air conditioning installations reflecting average concentrations per 3 months in different large cities. This approach is expected to be upgraded and applied for global monitoring. Highly positive correlated elements were found in lichens such as K/S, Zn/P, the rare earth elements (REE) and a significant negative correlation between Hg and Cu was observed in these samples. The ratio of concentrations of elements in dust and Usnea spp. is highest for Cz, Zn and Fe (400-200) and lowest for elements such as Ca, Rb, and Sr (20-10). PMID:10474261

  18. Pathway and Network Analysis in Proteomics

    PubMed Central

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

    2014-01-01

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

  19. Pathway and network analysis in proteomics.

    PubMed

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

    2014-12-01

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

  20. Pathway-PDT: a flexible pathway analysis tool for nuclear families

    PubMed Central

    2013-01-01

    Background Pathway analysis based on Genome-Wide Association Studies (GWAS) data has become popular as a secondary analysis strategy. Although many pathway analysis tools have been developed for case–control studies, there is no tool that can use all information from raw genotypes in general nuclear families. We developed Pathway-PDT, which uses the framework of Pedigree Disequilibrium Test (PDT) for general family data, to perform pathway analysis based on raw genotypes in family-based GWAS. Results Simulation results showed that Pathway-PDT is more powerful than the p-value based method, ALIGATOR. Pathway-PDT also can be more powerful than the PLINK set-based test when analyzing general nuclear families with multiple siblings or missing parents. Additionally, Pathway-PDT has a flexible and convenient user interface, which allows users to modify their analysis parameters as well as to apply various types of gene and pathway definitions. Conclusions The Pathway-PDT method is implemented in C++ with POSIX threads and is computationally feasible for pathway analysis with large scale family GWAS datasets. The Windows binary along with Makefile and source codes for the Linux are available at https://sourceforge.net/projects/pathway-pdt/. PMID:24006871

  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. On the pathways and timescales of intercontinental air pollution transport

    NASA Astrophysics Data System (ADS)

    Stohl, Andreas; Eckhardt, Sabine; Forster, Caroline; James, Paul; Spichtinger, Nicole

    2002-12-01

    This paper presents results of a 1-year simulation of the transport of six passive tracers, released over the continents according to an emission inventory for carbon monoxide (CO). Lagrangian concepts are introduced to derive age spectra of the tracer concentrations on a global grid in order to determine the timescales and pathways of pollution export from the continents. Calculating these age spectra is equivalent to simulating many (quasi continuous) plumes, each starting at a different time, which are subsequently merged. Movies of the tracer dispersion have been made available on an Internet website. It is found that emissions from Asia experience the fastest vertical transport, whereas European emissions have the strongest tendency to remain in the lower troposphere. European emissions are transported primarily into the Arctic and appear to be the major contributor to the Arctic haze problem. Tracers from an upwind continent first arrive over a receptor continent in the upper troposphere, typically after some 4 days. Only later foreign tracers also arrive in the lower troposphere. Assuming a 2-day lifetime, the domestic tracers dominate total tracer columns over all continents except over Australia where foreign tracers account for 20% of the tracer mass. In contrast, for a 20-day lifetime even continents with high domestic emissions receive more than half of their tracer burden from foreign continents. Three special regions were identified where tracers are transported to, and tracer dilution is slow. Future field studies therefore should be deployed in the following regions: (1) In the winter, the Asia tracer accumulates over Indonesia and the Indian Ocean, a region speculated to be a stratospheric fountain. (2) In the summer, the highest concentrations of the Asia tracer are found in the Middle East. (3) In the summer, the highest concentrations of the North America tracer are found in the Mediterranean.

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

    PubMed

    Lin, Peng-Lin; Yu, Ya-Wen; Chung, Ren-Hua

    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

  4. 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.

  5. Interfacing air pathway models with other media models for impact assessment

    SciTech Connect

    Drake, R.L.

    1980-10-01

    The assessment of the impacts/effects of a coal conversion industry on human health, ecological systems, property and aesthetics requires knowledge about effluent and fugitive emissions, dispersion of pollutants in abiotic media, chemical and physical transformations of pollutants during transport, and pollutant fate passing through biotic pathways. Some of the environmental impacts that result from coal conversion facility effluents are subtle, acute, subacute or chronic effects in humans and other ecosystem members, acute or chronic damage of materials and property, odors, impaired atmospheric visibility, and impacts on local, regional and global weather and climate. This great variety of impacts and effects places great demands on the abiotic and biotic numerical simulators (modelers) in terms of time and space scales, transformation rates, and system structure. This paper primarily addresses the demands placed on the atmospheric analyst. The paper considers the important air pathway processes, the interfacing of air pathway models with other media models, and the classes of air pathway models currently available. In addition, a strong plea is made for interaction and communication between all modeling groups to promote efficient construction of intermedia models that truly interface across pathway boundaries.

  6. GIS implementation in air pollution analysis

    SciTech Connect

    Chaaban, F.G.

    1998-07-01

    Air quality modeling and simulation is an indispensable tool used in different environmental studies that attempt to estimate air pollution levels caused by existing or planned combustion processes, to evaluate proposed emission reduction technologies, to select sites for new emission sources, and accordingly to establish emission control strategies in different energy conversion sectors. Modeling techniques, based on established mathematical formulation, are widely used for simulating air pollution caused mainly by the transportation and electric power sectors. Geographic information systems, GIS, link spatial information to alphanumeric information thus developing geographically referenced database. GIS systems have already been incorporated successfully into several fields in the energy sector and are proven to be a very efficient and robust tool for relevant analysis. In the environmental studies, GIS can answer many questions related to air pollution such as pollution sources as well as identification of regions in which the concentration may exceed limits set by local and international standards. The work presented in this paper is aimed at integrating GIS into air pollution analysis. The main objective is to estimate, using advanced graphical illustrations, the concentration levels of different types of air effluents emitted from point, line, or area sources. The integrated package is then used to examine the influence of various mitigation strategies on the air pollutants levels, and hence to evaluate the effectiveness of these strategies. The paper is concluded by case studies from the transportation and power sectors.

  7. Identification of disturbed pathways in heart failure based on Gibbs sampling and pathway enrichment analysis.

    PubMed

    Chen, P; Guo, L H; Guo, Y K; Qu, Z J; Gao, Y; Qiu, H

    2016-01-01

    We identified disturbed pathways in heart failure (HF) based on Gibbs sampling combined with pathway enrichment analysis. A total of 396 Markov chains (MCs) (gene count >5) were obtained. After Gibbs sampling, six differentially expressed molecular functions (DEMFs) (possibility ≥0.8) were obtained. As statistical analysis was performed on the number of individual differentially expressed genes (DEGs), we found that there were 137 DEGs with frequency of occurrence ≥2 in the DEMFs. Pathway enrichment analysis showed that these 137 DEGs were enriched in eight significant pathways under the condition of P < 0.001. The five most significant pathways were: the calcium signaling pathway (P = 9.08E-19), arrhythmogenic right ventricular cardiomyopathy (P = 5.66E-13), cardiac muscle contraction (P = 8.04E-13), hypertrophic cardiomyopathy (P = 2.55E-12), and dilated cardiomyopathy (P = 7.30E-12). In conclusion, this novel method for identifying significant pathways in HF based on Gibbs sampling combined with pathway enrichment analysis was suitable. We predict that several altered pathways (such as the calcium signaling pathway and dilated cardiomyopathy) may play important roles in HF and are potentially novel predictive and prognostic markers for HF. PMID:27173293

  8. Thermal analysis of car air conditioning

    NASA Astrophysics Data System (ADS)

    Trzebiński, Daniel; Szczygieł, Ireneusz

    2010-10-01

    Thermodynamic analysis of car air cooler is presented in this paper. Typical refrigerator cycles are studied. The first: with uncontrolled orifice and non controlled compressor and the second one with the thermostatic controlled expansion valve and externally controlled compressor. The influence of the refrigerant decrease and the change of the air temperature which gets to exchangers on the refrigeration efficiency of the system; was analysed. Also, its effectiveness and the power required to drive the compressor were investigated. The impact of improper refrigerant charge on the performance of air conditioning systems was also checked.

  9. 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. PMID:26782201

  10. Automatic variance analysis of multistage care pathways.

    PubMed

    Li, Xiang; Liu, Haifeng; Zhang, Shilei; Mei, Jing; Xie, Guotong; Yu, Yiqin; Li, Jing; Lakshmanan, Geetika T

    2014-01-01

    A care pathway (CP) is a standardized process that consists of multiple care stages, clinical activities and their relations, aimed at ensuring and enhancing the quality of care. However, actual care may deviate from the planned CP, and analysis of these deviations can help clinicians refine the CP and reduce medical errors. In this paper, we propose a CP variance analysis method to automatically identify the deviations between actual patient traces in electronic medical records (EMR) and a multistage CP. As the care stage information is usually unavailable in EMR, we first align every trace with the CP using a hidden Markov model. From the aligned traces, we report three types of deviations for every care stage: additional activities, absent activities and violated constraints, which are identified by using the techniques of temporal logic and binomial tests. The method has been applied to a CP for the management of congestive heart failure and real world EMR, providing meaningful evidence for the further improvement of care quality. PMID:25160280

  11. 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.

  12. An analysis of air-turborocket performance

    NASA Astrophysics Data System (ADS)

    Bussi, Giuseppe; Colasurdo, Guido; Pastrone, Dario

    1993-06-01

    In order to assess the capabilities of the air-turborocket, an off-design analysis of a representative LOX-LH2 fed engine is carried out. Working lines on an envisageable compressor map are drawn for different flight conditions along a typical transatmospheric vehicle flight path. Characteristic aspects of the air-turborocket behavior in the spontaneous and controlled mode are highlighted. Specific thrust and propellant consumption at full throttle are computed, both in the dry and augmented mode. Performance achievable by exploiting the permissible mass flow range of the compressor map via the variation of the nozzle throat area, is shown.

  13. Pathway alignment: application to the comparative analysis of glycolytic enzymes.

    PubMed Central

    Dandekar, T; Schuster, S; Snel, B; Huynen, M; Bork, P

    1999-01-01

    Comparative analysis of metabolic pathways in different genomes yields important information on their evolution, on pharmacological targets and on biotechnological applications. In this study on glycolysis, three alternative ways of comparing biochemical pathways are combined: (1) analysis and comparison of biochemical data, (2) pathway analysis based on the concept of elementary modes, and (3) a comparative genome analysis of 17 completely sequenced genomes. The analysis reveals a surprising plasticity of the glycolytic pathway. Isoenzymes in different species are identified and compared; deviations from the textbook standard are detailed. Several potential pharmacological targets and by-passes (such as the Entner-Doudoroff pathway) to glycolysis are examined and compared in the different species. Archaean, bacterial and parasite specific adaptations are identified and described. PMID:10493919

  14. The impact of circulation patterns on regional transport pathways and air quality over Beijing and its surroundings

    NASA Astrophysics Data System (ADS)

    Zhang, J. P.; Zhu, T.; Zhang, Q. H.; Li, C. C.; Shu, H. L.; Ying, Y.; Dai, Z. P.; Wang, X.; Liu, X. Y.; Liang, A. M.; Shen, H. X.; Yi, B. Q.

    2012-06-01

    This study investigated the air pollution characteristics of synoptic-scale circulation in the Beijing megacity, and provided quantitative evaluation of the impacts of circulation patterns on air quality during the 2008 Beijing Summer Olympics. Nine weather circulation types (CTs) were objectively identified over the North China region during 2000-2009, using obliquely rotated T-mode principal component analysis (PCA). The resulting CTs were examined in relation to the local meteorology, regional transport pathways, and air quality parameters, respectively. The FLEXPART-WRF model was used to calculate 48-h backward plume trajectories for each CT. Each CT was characterized with distinct local meteorology and air mass origin. CT 1 (high pressure to the west with a strong pressure gradient) was characterized by a northwestern air mass origin, with the smallest local and southeasterly air mass sources, and CT 6 (high pressure to the northwest) had air mass sources mostly from the north and east. On the contrary, CTs 5, 8, and 9 (weak pressure field, high pressure to the east, and low pressure to the northwest, respectively) were characterized by southern and southeastern trajectories, which indicated a greater influence of high pollutant emission sources. In turn, poor air quality in Beijing (high loadings of PM10, BC, SO2, NO2, NOx, O3, AOD, and low visibility) was associated with these CTs. Good air quality in Beijing was associated with CTs 1 and 6. The average visibilities (with ±1σ) in Beijing for CTs 1 and 6 during 2000-2009 were 18.5 ± 8.3 km and 14.3 ± 8.5 km, respectively. In contrast, low visibility values of 6.0 ± 3.5 km, 6.6 ± 3.7 km, and 6.7 ± 3.6 km were found in CTs 5, 8, and 9, respectively. The mean concentrations of PM10 for CTs 1, 6, 5, 8, and 9 during 2005-2009 were 90.3 ± 76.3 μg m-3, 111.7 ± 89.6 μg m-3, 173.4 ± 105.8 μg m-3, 158.4 ± 90.0 μg m-3, and 151.2 ± 93.1 μg m-3, respectively. Analysis of the relationship between

  15. 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.

  16. 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

  17. The impact of circulation patterns on regional transport pathways and air quality over Beijing and its surroundings

    NASA Astrophysics Data System (ADS)

    Zhang, J. P.; Zhu, T.; Zhang, Q. H.; Li, C. C.; Shu, H. L.; Ying, Y.; Dai, Z. P.; Liu, X. Y.; Liang, A. M.; Shen, H. X.

    2011-12-01

    This study investigated the air pollution characteristics of synoptic-scale circulation in the Beijing megacity, and provided holistic evaluation of the impacts of circulation patterns on air quality during the 2008 Beijing Summer Olympics. Nine weather circulation types (CTs) were objectively identified over the North China region during 2000-2009, using obliquely rotated T-mode principal component analysis (PCA). The resulting CTs were examined in relation to the local meteorology, regional transport pathways, and air quality parameters, respectively. The FLEXPART-WRF model was used to calculate 48-h backward plume trajectories for each CT. Nine CTs were characterized, with distinct local meteorology and air mass origins. CT 1 (high to the west with a strong pressure gradient) was characterized by a northwestern origin, with the smallest local and southeasterly air mass sources, and CT 6 (high to the northwest) had air mass sources mostly from the north and east. In contrast, CTs 5, 8, and 9 (unique, high to the east, and low to the northwest, respectively) were characterized by southern and southeastern trajectories, which indicated a greater influence of high pollutant emission sources. In turn, poor air quality in Beijing (high loadings of PM10, BC, SO2, NO2, O3, AOD, and low visibility) was associated with these CTs. Good air quality in Beijing was associated with CTs 1 and 6. The average visibilities (with ±1 σ) in Beijing for CTs 1 and 6 during 2000-2009 were 18.5 ± 8.3 km and 14.3 ± 8.5 km, respectively. In contrast, poor visibility values of 6.0 ± 3.5 km, 6.6 ± 3.7 km, and 6.7 ± 3.6 km were found in CTs 5, 8, and 9, respectively. The mean concentrations of PM10 for CTs 1, 6, 5, 8, and 9 during 2005-2009 were 90.3 ± 76.3 μg m-3, 111.7 ± 89.6 μg m-3, 173.4 ± 105.8 μg m-3, 158.4 ± 90.0 μg m-3, and 151.2 ± 93.1 μg m-3, respectively. Analysis of the relationship between circulation pattern and air quality during the emission control period

  18. 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. PMID:27004716

  19. 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.

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

    PubMed

    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

  1. 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

  2. Chemical pathway analysis of the Martian atmosphere: CO2-formation pathways

    NASA Astrophysics Data System (ADS)

    Stock, Joachim W.; Boxe, Christopher S.; Lehmann, Ralph; Grenfell, J. Lee; Patzer, A. Beate C.; Rauer, Heike; Yung, Yuk L.

    2012-05-01

    The chemical composition of a planetary atmosphere plays an important role for atmospheric structure, stability, and evolution. Potentially complex interactions between chemical species do not often allow for an easy understanding of the underlying chemical mechanisms governing the atmospheric composition. In particular, trace species can affect the abundance of major species by acting in catalytic cycles. On Mars, such cycles even control the abundance of its main atmospheric constituent CO2. The identification of catalytic cycles (or more generally chemical pathways) by hand is quite demanding. Hence, the application of computer algorithms is beneficial in order to analyze complex chemical reaction networks. Here, we have performed the first automated quantified chemical pathways analysis of the Martian atmosphere with respect to CO2-production in a given reaction system. For this, we applied the Pathway Analysis Program (PAP) to output data from the Caltech/JPL photochemical Mars model. All dominant chemical pathways directly related to the global CO2-production have been quantified as a function of height up to 86 km. We quantitatively show that CO2-production is dominated by chemical pathways involving HOx and Ox. In addition, we find that NOx in combination with HOx and Ox exhibits a non-negligible contribution to CO2-production, especially in Mars' lower atmosphere. This study reveals that only a small number of chemical pathways contribute significantly to the atmospheric abundance of CO2 on Mars; their contributions to CO2-production vary considerably with altitude. This analysis also endorses the importance of transport processes in governing CO2-stability in the Martian atmosphere. Lastly, we identify a previously unknown chemical pathway involving HOx, Ox, and HO2-photodissociation, contributing 8% towards global CO2-production by chemical pathways using recommended up-to-date values for reaction rate coefficients.

  3. Air Force geographic information and analysis system

    SciTech Connect

    Henney, D.A.; Jansing, D.S.; Durfee, R.C.; Margle, S.M.; Till, L.E.

    1987-01-01

    A microcomputer-based geographic information and analysis system (GIAS) was developed to assist Air Force planners with environmental analysis, natural resources management, and facility and land-use planning. The system processes raster image data, topological data structures, and geometric or vector data similar to that produced by computer-aided design and drafting (CADD) systems, integrating the data where appropriate. Data types included Landsat imagery, scanned images of base maps, digitized point and chain features, topographic elevation data, USGS stream course data, highway networks, railroad networks, and land use/land cover information from USGS interpreted aerial photography. The system is also being developed to provide an integrated display and analysis capability with base maps and facility data bases prepared on CADD systems. 3 refs.

  4. 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.

  5. 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.

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

    PubMed Central

    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. PMID:26782201

  7. 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. PMID:24099652

  8. 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. PMID:26743605

  9. Chemical pathway analysis of Titan's upper atmosphere: Oxygen species

    NASA Astrophysics Data System (ADS)

    Stock, J. W.; Lara, L. M.; Lehmann, R.

    2014-04-01

    CO, CO2, and H2O are the only oxygen bearing species in Titan's atmosphere which have been clearly detected so far. Their abundances are controlled by the interaction of external and internal sources, photochemistry and condensation. In this contribution, we determine all significant chemical pathways responsible for the production and consumption of CO, CO2, and H2O. Furthermore, we investigate the effects of different oxygen sources on the efficiencies of the pathways. In order to achieve this, we apply a unique algorithm, called the Pathway Analysis Program - PAP to the results of a 1D photochemical model of Titan's atmosphere.

  10. 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

    2016-09-01

    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. PMID:27509207

  11. Genetic analysis of biological pathway data through genomic randomization

    PubMed Central

    Yaspan, Brian L.; Bush, William S.; Torstenson, Eric S.; Ma, Deqiong; Pericak-Vance, Margaret A.; Ritchie, Marylyn D.; Sutcliffe, James S.; Haines, Jonathan L.

    2011-01-01

    Genome Wide Association Studies (GWAS) are a standard approach for large-scale common variation characterization and for identification of single loci predisposing to disease. However, due to issues of moderate sample sizes and particularly multiple testing correction, many variants of smaller effect size are not detected within a single allele analysis framework. Thus, small main effects and potential epistatic effects are not consistently observed in GWAS using standard analytical approaches that consider only single SNP alleles. Here we propose unique methodology that aggregates variants of interest (for example, genes in a biological pathway) using GWAS results. Multiple testing and type I error concerns are minimized using empirical genomic randomization to estimate significance. Randomization corrects for common pathway-based analysis biases such as SNP coverage and density, linkage disequilibrium, gene size and pathway size. PARIS (Pathway Analysis by Randomization Incorporating Structure) applies this randomization and in doing so directly accounts for linkage disequilibrium effects. PARIS is independent of association analysis method and is thus applicable to GWAS datasets of all study designs. Using the KEGG database as an example, we apply PARIS to the publicly available Autism Genetic Resource Exchange (AGRE) GWA dataset, revealing pathways with a significant enrichment of positive association results. PMID:21279722

  12. Two novel pathway analysis methods based on a hierarchical model

    PubMed Central

    Evangelou, Marina; Dudbridge, Frank; Wernisch, Lorenz

    2014-01-01

    Motivation: Over the past few years several pathway analysis methods have been proposed for exploring and enhancing the analysis of genome-wide association data. Hierarchical models have been advocated as a way to integrate SNP and pathway effects in the same model, but their computational complexity has prevented them being applied on a genome-wide scale to date. Methods: We present two novel methods for identifying associated pathways. In the proposed hierarchical model, the SNP effects are analytically integrated out of the analysis, allowing computationally tractable model fitting to genome-wide data. The first method uses Bayes factors for calculating the effect of the pathways, whereas the second method uses a machine learning algorithm and adaptive lasso for finding a sparse solution of associated pathways. Results: The performance of the proposed methods was explored on both simulated and real data. The results of the simulation study showed that the methods outperformed some well-established association methods: the commonly used Fisher’s method for combining P-values and also the recently published BGSA. The methods were applied to two genome-wide association study datasets that aimed to find the genetic structure of platelet function and body mass index, respectively. The results of the analyses replicated the results of previously published pathway analysis of these phenotypes but also identified novel pathways that are potentially involved. Availability: An R package is under preparation. In the meantime, the scripts of the methods are available on request from the authors. Contact: marina.evangelou@cimr.cam.ac.uk Supplementary Information: Supplementary data are available at Bioinformatics online. PMID:24123673

  13. 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.

  14. Pathway Analysis of Smoking Quantity in Multiple GWAS Identifies Cholinergic and Sensory Pathways

    PubMed Central

    Harari, Oscar; Wang, Jen-Chyong; Bucholz, Kathleen; Edenberg, Howard J.; Heath, Andrew; Martin, Nicholas G.; Pergadia, Michele L.; Montgomery, Grant; Schrage, Andrew; Bierut, Laura J.; Madden, Pamela F.; Goate, Alison M.

    2012-01-01

    Cigarette smoking is a common addiction that increases the risk for many diseases, including lung cancer and chronic obstructive pulmonary disease. Genome-wide association studies (GWAS) have successfully identified and validated several susceptibility loci for nicotine consumption and dependence. However, the trait variance explained by these genes is only a small fraction of the estimated genetic risk. Pathway analysis complements single marker methods by including biological knowledge into the evaluation of GWAS, under the assumption that causal variants lie in functionally related genes, enabling the evaluation of a broad range of signals. Our approach to the identification of pathways enriched for multiple genes associated with smoking quantity includes the analysis of two studies and the replication of common findings in a third dataset. This study identified pathways for the cholinergic receptors, which included SNPs known to be genome-wide significant; as well as novel pathways, such as genes involved in the sensory perception of smell, that do not contain any single SNP that achieves that stringent threshold. PMID:23227220

  15. 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.

  16. Sense and nonsense of pathway analysis software in proteomics.

    PubMed

    Müller, Thorsten; Schrötter, Andreas; Loosse, Christina; Helling, Stefan; Stephan, Christian; Ahrens, Maike; Uszkoreit, Julian; Eisenacher, Martin; Meyer, Helmut E; Marcus, Katrin

    2011-12-01

    New developments in proteomics enable scientists to examine hundreds to thousands of proteins in parallel. Quantitative proteomics allows the comparison of different proteomes of cells, tissues, or body fluids with each other. Analyzing and especially organizing these data sets is often a Herculean task. Pathway Analysis software tools aim to take over this task based on present knowledge. Companies promise that their algorithms help to understand the significance of scientist's data, but the benefit remains questionable, and a fundamental systematic evaluation of the potential of such tools has not been performed until now. Here, we tested the commercial Ingenuity Pathway Analysis tool as well as the freely available software STRING using a well-defined study design in regard to the applicability and value of their results for proteome studies. It was our goal to cover a wide range of scientific issues by simulating different established pathways including mitochondrial apoptosis, tau phosphorylation, and Insulin-, App-, and Wnt-signaling. Next to a general assessment and comparison of the pathway analysis tools, we provide recommendations for users as well as for software developers to improve the added value of a pathway study implementation in proteomic pipelines. PMID:21978018

  17. A pathway analysis of global aerosol processes

    NASA Astrophysics Data System (ADS)

    Schutgens, Nick; Stier, Philip

    2014-05-01

    smaller modes. Our analysis also suggests that coagulation serves mainly as a loss process for number densities and that it is a relatively unimportant contributor to composition changes of aerosol. Our results provide an objective way of complexity analysis in a global aerosol model and will be used in future work where we will reduce this complexity in ECHAM-HAM.

  18. 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.

  19. 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

  20. 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.

  1. AIR QUALITY FORECAST DATABASE AND ANALYSIS

    EPA Science Inventory

    In 2003, NOAA and EPA signed a Memorandum of Agreement to collaborate on the design and implementation of a capability to produce daily air quality modeling forecast information for the U.S. NOAA's ETA meteorological model and EPA's Community Multiscale Air Quality (CMAQ) model ...

  2. Desiccant Enhanced Evaporative Air Conditioning: Parametric Analysis and Design; Preprint

    SciTech Connect

    Woods, J.; Kozubal, E.

    2012-10-01

    This paper presents a parametric analysis using a numerical model of a new concept in desiccant and evaporative air conditioning. The concept consists of two stages: a liquid desiccant dehumidifier and a dew-point evaporative cooler. Each stage consists of stacked air channel pairs separated by a plastic sheet. In the first stage, a liquid desiccant film removes moisture from the process (supply-side) air through a membrane. An evaporatively-cooled exhaust airstream on the other side of the plastic sheet cools the desiccant. The second-stage indirect evaporative cooler sensibly cools the dried process air. We analyze the tradeoff between device size and energy efficiency. This tradeoff depends strongly on process air channel thicknesses, the ratio of first-stage to second-stage area, and the second-stage exhaust air flow rate. A sensitivity analysis reiterates the importance of the process air boundary layers and suggests a need for increasing airside heat and mass transfer enhancements.

  3. 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 ...

  4. 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

  5. Transcriptome meta-analysis reveals dysregulated pathways in nasopharyngeal carcinoma.

    PubMed

    Tulalamba, Warut; Larbcharoensub, Noppadol; Sirachainan, Ekaphop; Tantiwetrueangdet, Aunchalee; Janvilisri, Tavan

    2015-08-01

    Nasopharyngeal carcinoma (NPC) is a malignant cancer arising from the epithelial surface of the nasopharynx that mostly appears in advanced stages of the disease, leading to a poor prognosis. To date, a number of mRNA profiling investigations on NPC have been reported in order to identify suitable biomarkers for early detection. However, the results may be specific to each study with distinct sample types. In this study, an integrative meta-analysis of NPC transcriptome data was performed to determine dysregulated pathways, potentially leading to identification of molecular markers. Ten independent NPC gene expression profiling microarray datasets, including 135 samples from NPC cell lines, primary cell lines, and tissues were assimilated into a meta-analysis and cross-validation to identify a cohort of genes that were significantly dysregulated in NPC. Bioinformatics analyses of these genes revealed the significant pathways and individual players involving in cellular metabolism, cell cycle regulation, DNA repair, as well as ErbB pathway. Altogether, we propose that dysregulation of these molecular pathways in NPC might play a role in the NPC pathogenesis, providing clues, which could eventually translate into diagnostic and therapeutic approaches. PMID:25724187

  6. Transdominant genetic analysis of a growth control pathway

    PubMed Central

    Caponigro, Giordano; Abedi, Majid R.; Hurlburt, Anthony P.; Maxfield, Andrew; Judd, Weston; Kamb, Alexander

    1998-01-01

    Genetic selections that use proteinaceous transdominant inhibitors encoded by DNA libraries to cause mutant phenocopies may facilitate genetic analysis in traditionally nongenetic organisms. We performed a selection for random short peptides and larger protein fragments (collectively termed “perturbagens”) that inhibit the yeast pheromone response pathway. Peptide and protein fragment perturbagens that permit cell division in the presence of pheromone were recovered. Two perturbagens were derived from proteins required for pheromone response, and an additional two were derived from proteins that may negatively influence the pheromone response pathway. Furthermore, three known components of the pathway were identified as probable perturbagen targets based on physical interaction assays. Thus, by selection for transdominant inhibitors of pheromone response, multiple pathway components were identified either directly as gene fragments or indirectly as the likely targets of specific perturbagens. These results, combined with the results of previous work [Holzmayer, T. A., Pestov, D. G. & Roninson, I. B. (1992) Nucl. Acids. Res. 20, 711–717; Whiteway, M., Dignard, D. & Thomas, D. Y. (1992) Proc. Natl. Acad. Sci. USA 89, 9410–9414; and Gudkov, A. V., Kazarov, A. R., Thimmapaya, R., Axenovich, S. A., Mazo, I. A. & Roninson, I. B. (1994) Proc. Natl. Acad. Sci. USA 91, 3744–3748], suggest that transdominant genetic analysis of the type described here will be broadly applicable. PMID:9636180

  7. 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.

  8. PathVisio 3: An Extendable Pathway Analysis Toolbox

    PubMed Central

    Kutmon, Martina; van Iersel, Martijn P.; Bohler, Anwesha; Kelder, Thomas; Nunes, Nuno; Pico, Alexander R.; Evelo, Chris T.

    2015-01-01

    PathVisio is a commonly used pathway editor, visualization and analysis software. Biological pathways have been used by biologists for many years to describe the detailed steps in biological processes. Those powerful, visual representations help researchers to better understand, share and discuss knowledge. Since the first publication of PathVisio in 2008, the original paper was cited more than 170 times and PathVisio was used in many different biological studies. As an online editor PathVisio is also integrated in the community curated pathway database WikiPathways. Here we present the third version of PathVisio with the newest additions and improvements of the application. The core features of PathVisio are pathway drawing, advanced data visualization and pathway statistics. Additionally, PathVisio 3 introduces a new powerful extension systems that allows other developers to contribute additional functionality in form of plugins without changing the core application. PathVisio can be downloaded from http://www.pathvisio.org and in 2014 PathVisio 3 has been downloaded over 5,500 times. There are already more than 15 plugins available in the central plugin repository. PathVisio is a freely available, open-source tool published under the Apache 2.0 license (http://www.apache.org/licenses/LICENSE-2.0). It is implemented in Java and thus runs on all major operating systems. The code repository is available at http://svn.bigcat.unimaas.nl/pathvisio. The support mailing list for users is available on https://groups.google.com/forum/#!forum/wikipathways-discuss and for developers on https://groups.google.com/forum/#!forum/wikipathways-devel. PMID:25706687

  9. Impact pathway analysis: A tool for improving environmental decision processes

    SciTech Connect

    Rabl, A.; Peuportier, B.

    1995-09-01

    This paper proposes that, for installations with major health risks, it may be practical and desirable to demand that and environmental impact study demonstrate not only that the emissions respect all applicable regulations (as is current practice), but that it actually evaluate the impacts, using the impact pathway methodology (i.e., analyze the dispersion of pollutants and apply dose-response functions to quantify impacts on health, vegetation, etc.). As a case study the authors apply the impact pathway analysis to the emissions data for an incinerator of toxic chemical waste, and they obtain several interesting results that could resolve some of the issues raised during the authorization process. They argue that the uncertainties, even though large, do not negate the value of the information. The results of such an impact analysis could also be used to communicate the risks posed by a proposed installation, fi a generally accepted set of reference risks is developed.

  10. Pollutants in particulate and gaseous fractions of ambient air interfere with multiple signaling pathways in vitro.

    PubMed

    Novák, Jirí; Jálová, Veronika; Giesy, John P; Hilscherová, Klára

    2009-01-01

    Traditionally, contamination of air has been evaluated primarily by chemical analyses of indicator contaminants and these studies have focused mainly on compounds associated with particulates. Some reports have shown that air contaminants can produce specific biological effects such as toxicity mediated by the aryl hydrocarbon receptor (AhR) or modulation of the endocrine system. This study assessed the dioxin-like toxicity, anti-/estrogenicity, anti-/androgenicity and anti-/retinoic activity of both the particulate and gas phase fractions of air in two regions with different types of pollution sources and a background locality situated in an agricultural area of Central Europe. The first region (A) is known to be significantly contaminated by organochlorine pesticides and chemical industry. The other region (B) has been polluted by historical releases of PCBs, but the major current sources of contamination are probably combustion sources from local traffic and heating. Samples of both particle and gas fractions produced dioxin-like (AhR-mediated) activity, anti-estrogenic and antiandrogenic effects, but none had any effect on retinoid signaling. AhR-mediated activities were observed in all samples and the TEQ values were comparable in both fractions in region A, but significantly greater in the particulate fraction in region B. The greater AhR-mediated activity corresponded to a greater coincident antiestrogenicity of both phases in region B. Our study is the first report of antiestrogenicity and antiandrogenicity in ambient air. Anti-androgenicity was observed in the gas phase of all regions, while in the particulate phase only in one region due to the specific type of pollution in that area. Even though based on concentrations of individual compounds, except for the OCPs, the level of contamination of the two regions was similar, there were strong differences in responses in the bioassays between the two regions. Moreover, AhR-mediated activity and

  11. Exploring poly-beta-hydroxy-butyrate metabolism through network-based extreme pathway analysis.

    PubMed

    Ding, Dewu; Ding, Yanrui; Cai, Yujie; Chen, Shouwen; Xu, Wenbo

    2008-01-01

    The objective of this article is to obtain a more detailed insight into poly-beta-hydroxybutyrate (PHB) metabolism through network-based metabolic pathway analysis. We employ extreme pathways to perform this study, because calculating and interpreting extreme pathways is a promising way for pathway analysis and metabolic engineering. After giving an in silico model of butanoate metabolism of Bacillus thuringiensis 97-27 (btk), extreme pathways were calculated and classified. Furthermore, the type I and II extreme pathways were further classified and analyzed in detail based on their structure and functional capabilities. Besides "historical" biochemical pathways, the results also suggest that there are some novel pathways. PMID:18600631

  12. Commercial Building Design Pathways Using Optimization Analysis: Preprint

    SciTech Connect

    Long, N.; Hirsch, A.; Lobato, C.; Macumber, D.

    2010-08-01

    Whole-building simulation and analysis has demonstrated a significant energy savings potential in a wide variety of design projects. Commercial building design, however, traditionally integrates simulation and modeling analyses too late in the design process to make a substantial impact on energy use. The National Renewable Energy Laboratory (NREL) commercial building group created an optimization platform called Opt-E-Plus that uses multivariate and multi-objective optimization theory to navigate a large parameter space and find economically valid, energy-saving solutions. The analysis results provide designers and engineers valuable information that influences the design. The pathways are not full 'construction ready' design alternatives; rather, they offer guidance about performance and cost criteria to reach a range of energy and economic goals. Having this knowledge early in the design phase helps designers establish project goals and direct the design pathway before they make important decisions. Opt-E-Plus has been deployed on several projects, including a retrofit mixed-use building, a new NREL office building, and several nationwide design guides. Each of these projects had different design criteria, goals, and audiences. In each case the analysis results provided pathways that helped inform the design process.

  13. Thermodynamic Analysis of a Novel Liquid Air Energy Storage System

    NASA Astrophysics Data System (ADS)

    Xue, X. D.; Wang, S. X.; Zhang, X. L.; Cui, C.; Chen, L. B.; Zhou, Y.; Wang, J. J.

    In this study, a novel liquid air energy storage system for electrical power load shifting application is introduced. It is a combination of an air liquefaction cycle and a gas turbine power generation cycle without fuel combustion. Thermodynamic analysis is conducted to investigate the performance of this system. The results show that liquid air energy storage systems could be very effective systems for electrical power storage with high efficiency, high energy density and extensive application prospects.

  14. Analysis of PI3K pathway components in human cancers

    PubMed Central

    DARAGMEH, JAMILA; BARRIAH, WASEIM; SAAD, BASHAR; ZAID, HILAL

    2016-01-01

    Recent advances in genomics, proteomics, cell biology and biochemistry of tumors have revealed new pathways that are aberrantly activated in numerous cancer types. However, the enormous amount of data available in this field may mislead scientists in focused research. As cancer cell growth and progression is often dependent upon the phosphoinositide 3-kinase (PI3K)/AKT pathway, there has been extensive research into the proteins implicated in the PI3K pathway. Using data available in the Human Protein Atlas database, the current study investigated the expression of 25 key proteins that are known to be involved with PI3K pathway activation in a distinct group of 20 cancer types. These proteins are AKTIP, ARP1, BAD, GSK3A, GSK3B, MERTK-1, PIK3CA, PRR5, PSTPIP2, PTEN, FOX1, RHEB, RPS6KB1, TSC1, TP53, BCL2, CCND1, WFIKKN2, CREBBP, caspase-9, PTK2, EGFR, FAS, CDKN1A and XIAP. The analysis revealed pronounced expression of specific proteins in distinct cancer tissues, which may have the potential to serve as targets for treatments and provide insights into the molecular basis of cancer. PMID:27073576

  15. Parameter sensitivity analysis of IL-6 signalling pathways.

    PubMed

    Chu, Y; Jayaraman, A; Hahn, J

    2007-11-01

    Signal transduction pathways generally consist of a large number of individual components and have an even greater number of parameters describing their reaction kinetics. Although the structure of some signalling pathways can be found in the literature, many of the parameters are not well known and they would need to be re-estimated from experimental data for each specific case. However it is not feasible to estimate hundreds of parameters because of the cost of the experiments associated with generating data. Parameter sensitivity analysis can address this situation as it investigates how the system behaviour is changed by variations of parameters and the analysis identifies which parameters play a key role in signal transduction. Only these important parameters need then be re-estimated using data from further experiments. This article presents a detailed parameter sensitivity analysis of the JAK/STAT and MAPK signal transduction pathway that is used for signalling by the cytokine IL-6. As no parameter sensitivity analysis technique is known to work best for all situations, a comparison of the results returned by four techniques is presented: differential analysis, the Morris method, a sampling-based approach and the Fourier amplitude sensitivity test. The recruitment of the transcription factor STAT3 to the dimer of the phosphorylated receptor complex is determined as the most important step by the sensitivity analysis. Additionally, the desphosphorylation of the nuclear STAT3 dimer by PP2 as well as feedback inhibition by SOCS3 are found to play an important role for signal transduction. PMID:18203580

  16. Identification of potential inhibitors for AIRS from de novo purine biosynthesis pathway through molecular modeling studies - a computational approach.

    PubMed

    Rao, R Guru Raj; Biswal, Jayashree; Dhamodharan, Prabhu; Kanagarajan, Surekha; Jeyaraman, Jeyakanthan

    2016-10-01

    In cancer, de novo pathway plays an important role in cell proliferation by supplying huge demand of purine nucleotides. Aminoimidazole ribonucleotide synthetase (AIRS) catalyzes the fifth step of de novo purine biosynthesis facilitating in the conversion of formylglycinamidine ribonucleotide to aminoimidazole ribonucleotide. Hence, inhibiting AIRS is crucial due to its involvement in the regulation of uncontrollable cancer cell proliferation. In this study, the three-dimensional structure of AIRS from P. horikoshii OT3 was constructed based on the crystal structure from E. coli and the modeled protein is verified for stability using molecular dynamics for a time frame of 100 ns. Virtual screening and induced fit docking were performed to identify the best antagonists based on their binding mode and affinity. Through mutational studies, the residues necessary for catalytic activity of AIRS were identified and among which the following residues Lys35, Asp103, Glu137, and Thr138 are important in determination of AIRS function. The mutational studies help to understand the structural and energetic characteristics of the specified residues. In addition to Molecular Dynamics, ADME properties, binding free-energy, and density functional theory calculations of the compounds were carried out to find the best lead molecule. Based on these analyses, the compound from the NCI database, NCI_121957 was adjudged as the best molecule and could be suggested as the suitable inhibitor of AIRS. In future studies, experimental validation of these ligands as AIRS inhibitors will be carried out. PMID:26524231

  17. TAPAS: Topographic air pollution analysis system. Technical note

    SciTech Connect

    Riebau, A.; Fox, D.A.; Marlatt, W.E.

    1987-05-01

    This report presents information on the Topographic Air Pollution Analysis System (TAPAS), currentlu under development by the Bureau of Land Management, U.S. Forest Service, and Colorado State University. TAPAS is designed to provide resource managers with air quality dispersion modeling tools to accomplish more efficient and economical air resource studies. TAPAS consists of a group of interactive air quality computer models that can be operated independently, or in combination for more detailed applications. TAPAS applications include support for resource management plans, environmental impact statements, siting of remote automatic weather stations, PSD permit evaluations, and smoke management for prescribed burns.

  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. 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.

  20. SYSTEMATIC SENSITIVITY ANALYSIS OF AIR QUALITY SIMULATION MODELS

    EPA Science Inventory

    This report reviews and assesses systematic sensitivity and uncertainty analysis methods for applications to air quality simulation models. The discussion of the candidate methods presents their basic variables, mathematical foundations, user motivations and preferences, computer...

  1. 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

  2. AIR INGRESS ANALYSIS: COMPUTATIONAL FLUID DYNAMIC MODELS

    SciTech Connect

    Chang H. Oh; Eung S. Kim; Richard Schultz; Hans Gougar; David Petti; Hyung S. Kang

    2010-08-01

    The Idaho National Laboratory (INL), under the auspices of the U.S. Department of Energy, is performing research and development that focuses on key phenomena important during potential scenarios that may occur in very high temperature reactors (VHTRs). Phenomena Identification and Ranking Studies to date have ranked an air ingress event, following on the heels of a VHTR depressurization, as important with regard to core safety. Consequently, the development of advanced air ingress-related models and verification and validation data are a very high priority. Following a loss of coolant and system depressurization incident, air will enter the core of the High Temperature Gas Cooled Reactor through the break, possibly causing oxidation of the in-the core and reflector graphite structure. Simple core and plant models indicate that, under certain circumstances, the oxidation may proceed at an elevated rate with additional heat generated from the oxidation reaction itself. Under postulated conditions of fluid flow and temperature, excessive degradation of the lower plenum graphite can lead to a loss of structural support. Excessive oxidation of core graphite can also lead to the release of fission products into the confinement, which could be detrimental to a reactor safety. Computational fluid dynamic model developed in this study will improve our understanding of this phenomenon. This paper presents two-dimensional and three-dimensional CFD results for the quantitative assessment of the air ingress phenomena. A portion of results of the density-driven stratified flow in the inlet pipe will be compared with results of the experimental results.

  3. Air Ingress Analysis: Part 1 - Theoretical Approach

    SciTech Connect

    Chang Ho Oh

    2011-01-01

    Idaho National Laboratory (INL), under the auspices of the U.S. Department of Energy (DOE), is performing research and development that focuses on key phenomena important during potential scenarios that may occur in very high temperature gas-cooled reactors (VHTRs). Phenomena identification and ranking studies to date have ranked an air ingress event, following on the heels of a VHTR depressurization, as important with regard to core safety. Consequently, the development of advanced air-ingress-related models and verification and validation data are a very high priority. Following a loss of coolant and system depressurization incident, air will enter the core of the VHTR through the break, possibly causing oxidation of the graphite core and reflector graphite structure. Simple core and plant models indicate that, under certain circumstances, the oxidation may proceed at an elevated rate with additional heat generated from the oxidation reaction itself. Under postulated conditions of fluid flow and temperature, excessive degradation of lower plenum graphite caused by graphite oxidation can lead to a loss of mechanical strength. Excessive oxidation of core graphite can also lead to a release of fission products into the confinement, which could be detrimental to reactor safety. Analytical models developed in this study will improve our understanding of this phenomenon. This paper presents two sets of analytical models for the qualitative assessment of the air ingress phenomena. The results from the analytical models are compared with results of the computational fluid dynamic models (CFD) in the subsequent paper. The analytical models agree well with those CFD results.

  4. Integrative analysis of genome-wide association studies and gene expression analysis identifies pathways associated with rheumatoid arthritis

    PubMed Central

    Li, Jin; Jiang, Yongshuai; Zhang, Ruijie

    2016-01-01

    Rheumatoid arthritis (RA) is a complex and systematic autoimmune disease, which is usually influenced by both genetic and environmental factors. Pathway analyses based on a single data type such as microarray data or SNP data have successfully revealed some biology pathways associated with RA. However, we found that the pathway analysis based on a single data type only provide limited understanding about the pathogenesis of RA. Gene-disease association is usually caused by many ways, such as genotype, gene expression and so on. Therefore, the integrative analysis method combining multiple levels of evidence can more precisely and comprehensively identify the pathway associations. In this study, we performed a pathway analysis by integrating GWAS and gene expression analysis to detect the RA-related pathways. The integrative analysis identified 28 pathways associated with RA. Among these pathways, 18 pathways were also found by both GWAS and gene expression analysis, 7 pathways are novel RA-related pathways, such as B cell receptor signaling pathway, Toll-like receptor signaling pathway, Fc gamma R-mediated phagocytosis and so on. Compared with pathway analyses using only one type genomic data, we found integrative analysis can increase the power to identify the real associations and provided more stable and accurate results. We believe these results will contribute to perform future genetic studies in RA pathogenesis and may promote the development of new therapeutic strategies by targeting these pathways. PMID:26885899

  5. 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.

  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. PMID:24552967

  7. Metabolic flux analysis of diterpene biosynthesis pathway in rice.

    PubMed

    Chang, Yung-Jin; Kim, Bo-Ra; Kim, Soo-Un

    2005-09-01

    Relative transcript levels of eight rice diterpene cyclases at the branch points of gibberellins and phytoalexins biosynthesis pathway were measured by reverse transcription quantitative PCR. Metabolic flux analysis by the distribution ratio of common substrate showed that UV-irradiation of etiolated rice seedlings decreased the flux for primary metabolism of gibberellins biosynthesis by half (from 62 to 27%) and 41% of geranylgeranyl pyrophosphate was used for induction of pimaradiene intermediate as the major phytoalexin. In comparison, light-illumination used almost all geranylgeranyl pyrophosphate (96%) for gibberellin biosynthesis to stimulate the plant growth and strongly repressed the metabolic flux for phytoalexins biosynthesis. PMID:16215852

  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. 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.

  11. 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. PMID:21684221

  12. Identifiability and inference of pathway motifs by epistasis analysis.

    PubMed

    Phenix, Hilary; Perkins, Theodore; Kærn, Mads

    2013-06-01

    The accuracy of genetic network inference is limited by the assumptions used to determine if one hypothetical model is better than another in explaining experimental observations. Most previous work on epistasis analysis-in which one attempts to infer pathway relationships by determining equivalences among traits following mutations-has been based on Boolean or linear models. Here, we delineate the ultimate limits of epistasis-based inference by systematically surveying all two-gene network motifs and use symbolic algebra with arbitrary regulation functions to examine trait equivalences. Our analysis divides the motifs into equivalence classes, where different genetic perturbations result in indistinguishable experimental outcomes. We demonstrate that this partitioning can reveal important information about network architecture, and show, using simulated data, that it greatly improves the accuracy of genetic network inference methods. Because of the minimal assumptions involved, equivalence partitioning has broad applicability for gene network inference. PMID:23822501

  13. Pathway analysis of genome-wide association study and transcriptome data highlights new biological pathways in colorectal cancer.

    PubMed

    Quan, Baoku; Qi, Xingsi; Yu, Zhihui; Jiang, Yongshuai; Liao, Mingzhi; Wang, Guangyu; Feng, Rennan; Zhang, Liangcai; Chen, Zugen; Jiang, Qinghua; Liu, Guiyou

    2015-04-01

    Colorectal cancer (CRC) is a common malignancy that meets the definition of a complex disease. Genome-wide association study (GWAS) has identified several loci of weak predictive value in CRC, however, these do not fully explain the occurrence risk. Recently, gene set analysis has allowed enhanced interpretation of GWAS data in CRC, identifying a number of metabolic pathways as important for disease pathogenesis. Whether there are other important pathways involved in CRC, however, remains unclear. We present a systems analysis of KEGG pathways in CRC using (1) a human CRC GWAS dataset and (2) a human whole transcriptome CRC case-control expression dataset. Analysis of the GWAS dataset revealed significantly enriched KEGG pathways related to metabolism, immune system and diseases, cellular processes, environmental information processing, genetic information processing, and neurodegenerative diseases. Altered gene expression was confirmed in these pathways using the transcriptome dataset. Taken together, these findings not only confirm previous work in this area, but also highlight new biological pathways whose deregulation is critical for CRC. These results contribute to our understanding of disease-causing mechanisms and will prove useful for future genetic and functional studies in CRC. PMID:25362561

  14. SPATIAL: A System-level PAThway Impact AnaLysis approach

    PubMed Central

    Bokanizad, Behzad; Tagett, Rebecca; Ansari, Sahar; Helmi, B. Hoda; Draghici, Sorin

    2016-01-01

    The goal of pathway analysis is to identify the pathways that are significantly impacted when a biological system is perturbed, e.g. by a disease or drug. Current methods treat pathways as independent entities. However, many signals are constantly sent from one pathway to another, essentially linking all pathways into a global, system-wide complex. In this work, we propose a set of three pathway analysis methods based on the impact analysis, that performs a system-level analysis by considering all signals between pathways, as well as their overlaps. Briefly, the global system is modeled in two ways: (i) considering the inter-pathway interaction exchange for each individual pathways, and (ii) combining all individual pathways to form a global, system-wide graph. The third analysis method is a hybrid of these two models. The new methods were compared with DAVID, GSEA, GSA, PathNet, Crosstalk and SPIA on 23 GEO data sets involving 19 tissues investigated in 12 conditions. The results show that both the ranking and the P-values of the target pathways are substantially improved when the analysis considers the system-wide dependencies and interactions between pathways. PMID:27193997

  15. 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.

  16. Identifiability and inference of pathway motifs by epistasis analysis

    NASA Astrophysics Data System (ADS)

    Phenix, Hilary; Perkins, Theodore; Kærn, Mads

    2013-06-01

    The accuracy of genetic network inference is limited by the assumptions used to determine if one hypothetical model is better than another in explaining experimental observations. Most previous work on epistasis analysis—in which one attempts to infer pathway relationships by determining equivalences among traits following mutations—has been based on Boolean or linear models. Here, we delineate the ultimate limits of epistasis-based inference by systematically surveying all two-gene network motifs and use symbolic algebra with arbitrary regulation functions to examine trait equivalences. Our analysis divides the motifs into equivalence classes, where different genetic perturbations result in indistinguishable experimental outcomes. We demonstrate that this partitioning can reveal important information about network architecture, and show, using simulated data, that it greatly improves the accuracy of genetic network inference methods. Because of the minimal assumptions involved, equivalence partitioning has broad applicability for gene network inference.

  17. 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

  18. Monitoring and analysis of air quality in Riga

    NASA Astrophysics Data System (ADS)

    Ubelis, Arnolds; Leitass, Andris; Vitols, Maris

    1995-09-01

    Riga, the capital of Latvia is a city with nearly 900,000 inhabitants and various highly concentrated industries. Air pollution in Riga is a serious problem affecting health and damaging valuable buildings of historical importance, as acid rain and smog take their toll. Therefore the Air Quality Management System with significant assistance from Swedish Government and persistent efforts from Riga City Council was arranged in Riga. It contains INDIC AIRVIRO system which simulates and evaluates air pollution levels at various locations. It then processes the data in order to predict air quality based on a number of criteria and parameters, measured by OPSIS differential absorption instruments, as well as data from the Meteorological Service and results of episodic measurements. The analysis of the results provided by Riga Air Quality Management System for the first time allows us to start comprehensive supervision of troposphere physical, chemical, and photochemical processes in the air of Riga as well as to appreciate the influence of lcoal pollution and transboundary transfer. The report contains the actual results of this work and first attempts of analysis as well as overview about activities towards research and teaching in the fields of spectroscopy and photochemistry of polluted atmospheres.

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

    PubMed

    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/m(3) 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

  20. 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.

  1. Analysis of Functional Pathways Altered after Mild Traumatic Brain Injury

    PubMed Central

    Redell, John B.; Moore, Anthony N.; Grill, Raymond J.; Johnson, Daniel; Zhao, Jing; Liu, Yin

    2013-01-01

    Abstract Concussive injury (or mild traumatic brain injury; mTBI) can exhibit features of focal or diffuse injury patterns. We compared and contrasted the cellular and molecular responses after mild controlled cortical impact (mCCI; a focal injury) or fluid percussion injury (FPI; a diffuse injury) in rats. The rationale for this comparative analysis was to investigate the brain's response to mild diffuse versus mild focal injury to identify common molecular changes triggered by these injury modalities and to determine the functional pathways altered after injury that may provide novel targets for therapeutic intervention. Microarrays containing probes against 21,792 unique messenger RNAs (mRNAs) were used to investigate the changes in cortical mRNA expression levels at 3 and 24 h postinjury. Of the 354 mRNAs with significantly altered expression levels after mCCI, over 89% (316 mRNAs) were also contained within the mild FPI (mFPI) data set. However, mFPI initiated a more widespread molecular response, with over 2300 mRNAs differentially expressed. Bioinformatic analysis of annotated Gene Ontology molecular function and biological pathway terms showed a significant overrepresentation of genes belonging to inflammation, stress, and signaling categories in both data sets. We therefore examined changes in the protein levels of a panel of 23 cytokines and chemokines in cortical extracts using a Luminex-based bead immunoassay and detected significant increases in macrophage inflammatory protein (MIP)-1α (CCL3), GRO-KC (CXCL1), interleukin (IL)-1α, IL-1β, and IL-6. Immunohistochemical localization of MIP-1α and IL-1β showed marked increases at 3 h postinjury in the cortical vasculature and microglia, respectively, that were largely resolved by 24 h postinjury. Our findings demonstrate that both focal and diffuse mTBI trigger many shared pathobiological processes (e.g., inflammatory responses) that could be targeted for mechanism-based therapeutic interventions

  2. 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.

  3. 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.

  4. Pulse Detonation Engine Air Induction System Analysis

    NASA Technical Reports Server (NTRS)

    Pegg, R. J.; Hunter, L. G.; Couch, B. D.

    1996-01-01

    A preliminary mixed-compression inlet design concept for potential pulse-detonation engine (PDE) powered supersonic aircraft was defined and analyzed. The objectives of this research were to conceptually design and integrate an inlet/PDE propulsion system into a supersonic aircraft, perform time-dependent CFD analysis of the inlet flowfield, and to estimate the installed PDE cycle performance. The study was baselined to a NASA Mach 5 Waverider study vehicle in which the baseline over/under turboramjet engines were replaced with a single flowpath PDE propulsion system. As much commonality as possible was maintained with the baseline configuration, including the engine location and forebody lines. Modifications were made to the inlet system's external ramp angles and a rotating cowl lip was incorporated to improve off-design inlet operability and performance. Engines were sized to match the baseline vehicle study's ascent trajectory thrust requirement at Mach 1.2. The majority of this study was focused on a flight Mach number of 3.0. The time-dependent Navier Stokes CFD analyses of a two-dimensional approximation of the inlet was conducted for the Mach 3.0 condition. The Lockheed Martin Tactical Aircraft Systems-developed FALCON CFD code with a two equation 'k-1' turbulence model was used. The downstream PDE was simulated by an array of four sonic nozzles in which the flow areas were rapidly varied in various opening/closing combinations. Results of the CFD study indicated that the inlet design concept operated successfully at the Mach 3.0 condition, satisfying mass capture, total pressure recovery, and operability requirements. Time-dependent analysis indicated that pressure and expansion waves from the simulated valve perturbations did not effect the inlet's operability or performance.

  5. A comparison of model predictions and observations of the transfer of /sup 137/Cs through the air-pasture-cow-milk pathway

    SciTech Connect

    Ng, Y.C.; Hoffman, F.O.

    1987-12-01

    Environmental measurements reported for selected locations in the United States and Europe following the Chernobyl accident were compared with model predictions of the transfer of /sup 137/Cs through the air-pasture-cow-milk pathway. The models evaluated include IAEA Safety Series No. 57, AIRDOS/EPA, NRC Regulatory Guides 1.109 and 1.111, the National Council on Radiation Protection and Measurements (NCRP) screening model, and the PATHWAY dynamic food-chain model. Time integrals of the /sup 137/Cs concentrations in air, pasture, and milk were estimated, and the predicted and observed grass/air, milk/air, and milk/grass concentration ratios were compared. Model predictions of the transfer of /sup 137/Cs from air to pasture and from pasture to milk tended to exceed observations. Those of PATHWAY were an exception; PATHWAY consistently underpredicted the grass/air and milk/air concentration ratios due to the use of parameter values specific for the deposition of large particles and their interception and retention by vegetation. Some of the models were flexible enough to permit parameter adjustment. In these cases, parameter values could be adjusted to the specific conditions determined for a location, which substantially reduced the discrepancy between predictions and observations. 22 refs., 8 tabs.

  6. 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…

  7. 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…

  8. 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

  9. Distribution, input pathway and soil-air exchange of polycyclic aromatic hydrocarbons in Banshan Industry Park, China.

    PubMed

    Zhong, Yuchi; Zhu, Lizhong

    2013-02-01

    Given the steel industry park-city paired structure commonly found across China and it associated environmental pollution, the objective of this study was to examine the spatial-temporal distributions of polycyclic aromatic hydrocarbons (PAHs) as well as the relative contributions of the main influx pathways in Banshan steel industry park, China. We analyzed the concentrations of 16 PAHs in soil, air, water and dry/wet deposition samples using gas chromatography-mass spectrometry (GC-MS). The concentrations of ∑(16)-PAHs ranged from 572 to 4,654 μg/kg in April 2010; and the average concentration is 12.7% and 26.1% higher than that of April 2009 and April 2008, respectively, mainly due to the rapid increase of highly toxic high molecular weight (MW) PAHs. The principal input pathway for high and low MW PAHs was determined to be dry deposition (e.g., 69.73% for Benzo[a]pyrene) and wet deposition (e.g., 78.87% for Naphthalene), respectively. Together, 54.79% of total PAHs found in this region are via dry deposition, whereas wet deposition and river water irrigation contribute to 25.46% and 19.76% (corrected with toxic equivalency factors). The approach to the soil-air equilibrium was assessed by calculating fugacity quotients between soil and air samples, and the results indicate that the soil acted as a secondary source for light MW atmospheric PAHs and a sink for higher MW PAHs. It was also determined that the soil acted as a source for median MW PAHs, particularly PY. PMID:23268144

  10. Automated retinofugal visual pathway reconstruction with multi-shell HARDI and FOD-based analysis.

    PubMed

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

    2016-01-15

    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

  11. Signalling pathway impact analysis based on the strength of interaction between genes.

    PubMed

    Bao, Zhenshen; Li, Xianbin; Zan, Xiangzhen; Shen, Liangzhong; Ma, Runnian; Liu, Wenbin

    2016-08-01

    Signalling pathway analysis is a popular approach that is used to identify significant cancer-related pathways based on differentially expressed genes (DEGs) from biological experiments. The main advantage of signalling pathway analysis lies in the fact that it assesses both the number of DEGs and the propagation of signal perturbation in signalling pathways. However, this method simplifies the interactions between genes by categorising them only as activation (+1) and suppression (-1), which does not encompass the range of interactions in real pathways, where interaction strength between genes may vary. In this study, the authors used newly developed signalling pathway impact analysis (SPIA) methods, SPIA based on Pearson correlation coefficient (PSPIA), and mutual information (MSPIA), to measure the interaction strength between pairs of genes. In analyses of a colorectal cancer dataset, a lung cancer dataset, and a pancreatic cancer dataset, PSPIA and MSPIA identified more candidate cancer-related pathways than were identified by SPIA. Generally, MSPIA performed better than PSPIA. PMID:27444024

  12. Genomic Gene Clustering Analysis of Pathways in Eukaryotes

    PubMed Central

    Lee, Jennifer M.; Sonnhammer, Erik L.L.

    2003-01-01

    Genomic clustering of genes in a pathway is commonly found in prokaryotes due to transcriptional operons, but these are not present in most eukaryotes. Yet, there might be clustering to a lesser extent of pathway members in eukaryotic genomes, that assist coregulation of a set of functionally cooperating genes. We analyzed five sequenced eukaryotic genomes for clustering of genes assigned to the same pathway in the KEGG database. Between 98% and 30% of the analyzed pathways in a genome were found to exhibit significantly higher clustering levels than expected by chance. In descending order by the level of clustering, the genomes studied were Saccharomyces cerevisiae, Homo sapiens, Caenorhabditis elegans, Arabidopsis thaliana, and Drosophila melanogaster. Surprisingly, there is not much agreement between genomes in terms of which pathways are most clustered. Only seven of 69 pathways found in all species were significantly clustered in all five of them. This species-specific pattern of pathway clustering may reflect adaptations or evolutionary events unique to a particular lineage. We note that although operons are common in C. elegans, only 58% of the pathways showed significant clustering, which is less than in human. Virtually all pathways in S. cerevisiae showed significant clustering. PMID:12695325

  13. 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

  14. 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.

  15. Abatement and degradation pathways of toluene in indoor air by positive corona discharge.

    PubMed

    Van Durme, J; Dewulf, J; Sysmans, W; Leys, C; Van Langenhove, H

    2007-08-01

    Indoor air concentrations of volatile organic compounds often exceed outdoor levels by a factor of 5. There is much interest in developing new technologies in order to improve indoor air quality. In this work non-thermal plasma (DC positive corona discharge) is explored as an innovative technology for indoor air purification. An inlet gas stream of 10 l min(-1) containing 0.50+/-0.02 ppm toluene was treated by the plasma reactor in atmospheric conditions. Toluene removal proved to be achievable with a characteristic energy density epsilon(0) of 50 J l(-1). Removal efficiencies were higher for 26% relative humidity (epsilon(0)=35 J l(-1)), compared with those at increased humidities (50% relative humidity, epsilon(0)=49 J l(-1)). Reaction products such as formic acid, benzaldehyde, benzyl alcohol, 3-methyl-4-nitrophenol, 4-methyl-2-nitrophenol, 4-methyl-2-propyl furan, 5-methyl-2-nitrophenol, 4-nitrophenol, 2-methyl-4,6-dinitrophenol are identified by means of mass spectrometry. Based on these by-products a toluene degradation mechanism is proposed. PMID:17490711

  16. 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

  17. 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

  18. A growing role for gender analysis in air pollution epidemiology.

    PubMed

    Clougherty, Jane E

    2011-04-01

    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. Studies of children suggest stronger effects among boys in early life and among girls in later childhood. 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. PMID:21584463

  19. Some improvements in air particulate matter analysis by INAA

    NASA Astrophysics Data System (ADS)

    Farinha, M. M.; Freitas, M. C.; Almeida, S. M.; Reis, M. A.

    2001-06-01

    At ITN, analysis of air particulate matter has been made since 1999, stimulated by a contract for air quality monitoring of an urban waste incinerator. Samples are analysed by Instrumental Neutron Activation Analysis (INAA) and Proton Induced X-ray Emission (PIXE). Heavy metals and other elements are determined. The procedures for filter analysis have recently been changed, leading to the present comparison between the old and the new procedures. For INAA, in this new procedure we look for the 336.2 keV gamma line of 115mIn in addition to the gamma-ray line of 527.9 keV used for the detection of 115Cd. Cd evaluations obtained by both gamma lines are compared and detection limits for Cd are presented. Preliminary results for Cd, As, Ni, and Hg are shown for a region in the north of Lisbon.

  20. 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.

  1. 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.

  2. Reverse engineering of Alzheimer's disease based on biomarker pathways analysis.

    PubMed

    Richens, Joanna L; Morgan, Kevin; O'Shea, Paul

    2014-09-01

    Alzheimer's disease (AD) poses an increasingly profound problem to society, yet progress toward a genuine understanding of the disease remains worryingly slow. Perhaps, the most outstanding problem with the biology of AD is the question of its mechanistic origins, that is, it remains unclear wherein the molecular failures occur that underlie the disease. We demonstrate how molecular biomarkers could help define the nature of AD in terms of the early biochemical events that correlate with disease progression. We use a novel panel of biomolecules that appears in cerebrospinal fluid of AD patients. As changes in the relative abundance of these molecular markers are associated with progression to AD from mild cognitive impairment, we make the assumption that by tracking their origins we can identify the biochemical conditions that predispose their presence and consequently cause the onset of AD. We couple these protein markers with an analysis of a series of genetic factors and together this hypothesis essentially allows us to redefine AD in terms of the molecular pathways that underlie the disease. PMID:24684789

  3. Reactome pathway analysis to enrich biological discovery in proteomics data sets.

    PubMed

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

    2011-09-01

    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-like visualization system that supports manual navigation of pathways by zooming, scrolling and event highlighting, and that exploits PSI Common Query Interface web services to overlay pathways with molecular interaction data from the Reactome Functional Interaction 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 data sets. 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 analysis of large-scale proteomics data sets. This Tutorial is part of the International Proteomics Tutorial Programme (IPTP 8). PMID:21751369

  4. Distributional Benefit Analysis of a National Air Quality Rule

    PubMed Central

    Post, Ellen S.; Belova, Anna; Huang, Jin

    2011-01-01

    Under Executive Order 12898, the U.S. Environmental Protection Agency (EPA) must perform environmental justice (EJ) reviews of its rules and regulations. EJ analyses address the hypothesis that environmental disamenities are experienced disproportionately by poor and/or minority subgroups. Such analyses typically use communities as the unit of analysis. While community-based approaches make sense when considering where polluting sources locate, they are less appropriate for national air quality rules affecting many sources and pollutants that can travel thousands of miles. We compare exposures and health risks of EJ-identified individuals rather than communities to analyze EPA’s Heavy Duty Diesel (HDD) rule as an example national air quality rule. Air pollutant exposures are estimated within grid cells by air quality models; all individuals in the same grid cell are assigned the same exposure. Using an inequality index, we find that inequality within racial/ethnic subgroups far outweighs inequality between them. We find, moreover, that the HDD rule leaves between-subgroup inequality essentially unchanged. Changes in health risks depend also on subgroups’ baseline incidence rates, which differ across subgroups. Thus, health risk reductions may not follow the same pattern as reductions in exposure. These results are likely representative of other national air quality rules as well. PMID:21776207

  5. Experimental and theoretical analysis results for high temperature air combustion

    SciTech Connect

    Tanigawa, Tadashi; Morita, Mitsunobu

    1998-07-01

    With Japan's preparation of its Action program to prevent global warming in 1990 and the holding of the United National Conference on Environment and Development (the Earth Summit) in 1992 as a backdrop, reflecting the global effort to protect the environment, a high performance industrial furnace development project was launched in 1993 by the New Energy and Industrial Technology Development Organization (NEDO). This project focuses on the development of a combustion technology which uses air that is preheated to extremely high temperatures (above 1,000 C), heretofore considered impossible. Not only can this technology reduce carbon dioxide emission, thought to cause the greenhouse effect, by over 30%, but it can also reduce nitrogen oxide emission by nearly half. This new technology makes use of the recently-developed high-cycle regenerative heat exchanger, for preheating the furnace air supply. This exchanger preheats air to above 1,000 C, much higher than for conventional furnaces, and then this air is injected with fuel. R and D data have shown that CO{sub 2} and NO{sub x} emissions can be reduced markedly. However, the theoretical analysis is yet to be made, thereby hampering efforts to have this advanced technology become widely adopted. This project accumulated new data related to uniform temperature distribution, high energy heat transfer and low NO{sub x} as common characteristics of high temperature air combustion.

  6. 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

  7. 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.

  8. Analysis of air mass trajectories in the northern plateau of the Iberian Peninsula

    NASA Astrophysics Data System (ADS)

    Pérez, Isidro A.; Sánchez, M. Luisa; García, M. Ángeles; Pardo, Nuria

    2015-11-01

    Air masses reaching the Iberian Peninsula, which is located between two continents and two seas, have been classified. 24-h backward air trajectories were calculated each hour for three years using the METEX model at a site in the centre of the northern plateau of the Iberian Peninsula where the air flow has scarcely been investigated to date. Rather than the usual Euclidean geometry, spherical trigonometry, together with the kernel regression method, was considered to calculate trajectory distances to the site. Numerical indicators allow for an accurate description of the results. Ranges surrounding the site from E to S evidenced a restriction in the movement of the arriving flow. However, the range to the N showed only a slight effect. A noticeable seasonal contrast was observed between winter, whose distances were the greatest, and summer, which displayed the shortest distances. Trajectory clusters, initially not considered in the METEX model, were obtained with different metrics to determine the air mass pathways reaching the site. Five clusters of trajectories were selected so as to easily explain the directions and distances covered. Regional and long range transport were observed in clusters from the NE, NW and SW. The NE cluster presented an orographic deviation and local processes were limited to the SE cluster. Finally, seasonal analysis revealed singular behaviour during autumn, when local processes centred on the N-S direction.

  9. 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

  10. Comprehensive transcriptomic analysis of molecularly targeted drugs in cancer for target pathway evaluation

    PubMed Central

    Mashima, Tetsuo; Ushijima, Masaru; Matsuura, Masaaki; Tsukahara, Satomi; Kunimasa, Kazuhiro; Furuno, Aki; Saito, Sakae; Kitamura, Masami; Soma-Nagae, Taeko; Seimiya, Hiroyuki; Dan, Shingo; Yamori, Takao; Tomida, Akihiro

    2015-01-01

    Targeted therapy is a rational and promising strategy for the treatment of advanced cancer. For the development of clinical agents targeting oncogenic signaling pathways, it is important to define the specificity of compounds to the target molecular pathway. Genome-wide transcriptomic analysis is an unbiased approach to evaluate the compound mode of action, but it is still unknown whether the analysis could be widely applicable to classify molecularly targeted anticancer agents. We comprehensively obtained and analyzed 129 transcriptomic datasets of cancer cells treated with 83 anticancer drugs or related agents, covering most clinically used, molecularly targeted drugs alongside promising inhibitors of molecular cancer targets. Hierarchical clustering and principal component analysis revealed that compounds targeting similar target molecules or pathways were clustered together. These results confirmed that the gene signatures of these drugs reflected their modes of action. Of note, inhibitors of oncogenic kinase pathways formed a large unique cluster, showing that these agents affect a shared molecular pathway distinct from classical antitumor agents and other classes of agents. The gene signature analysis further classified kinome-targeting agents depending on their target signaling pathways, and we identified target pathway-selective signature gene sets. The gene expression analysis was also valuable in uncovering unexpected target pathways of some anticancer agents. These results indicate that comprehensive transcriptomic analysis with our database (http://scads.jfcr.or.jp/db/cs/) is a powerful strategy to validate and re-evaluate the target pathways of anticancer compounds. PMID:25911996

  11. 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. PMID:25809424

  12. Numerical Analysis on Air Ingress Behavior in GTHTR300H

    SciTech Connect

    Tetsuaki Takeda; Xing Yan; Kazuhiko Kunitomi

    2006-07-01

    Japan Atomic Energy Agency (JAEA) has been developing the analytical code for the safety characteristics of the HTGR and carrying out design study of the gas turbine high temperature reactor of 300 MWe nominal-capacity for hydrogen production, the GTHTR300H (Gas Turbine High Temperature Reactor 300 for Hydrogen). The objective of this study is to clarify safety characteristics of the GTHTR300H for the pipe rupture accident. A numerical analysis of heat and mass transfer fluid flow with multi-component gas mixture has been performed to obtain the variation of the density of the gas mixture, and the onset time of natural circulation of air. From the results obtained in this analysis, it was found that the duration time of the air ingress by molecular diffusion would increase due to the existence of the recuperator in the GTHTR300H system. (authors)

  13. Time series analysis of air pollutants in Beirut, Lebanon.

    PubMed

    Farah, Wehbeh; Nakhlé, Myriam Mrad; Abboud, Maher; Annesi-Maesano, Isabella; Zaarour, Rita; Saliba, Nada; Germanos, Georges; Gerard, Jocelyne

    2014-12-01

    This study reports for the first time a time series analysis of daily urban air pollutant levels (CO, NO, NO2, O3, PM10, and SO2) in Beirut, Lebanon. The study examines data obtained between September 2005 and July 2006, and their descriptive analysis shows long-term variations of daily levels of air pollution concentrations. Strong persistence of these daily levels is identified in the time series using an autocorrelation function, except for SO2. Time series of standardized residual values (SRVs) are also calculated to compare fluctuations of the time series with different levels. Time series plots of the SRVs indicate that NO and NO2 had similar temporal fluctuations. However, NO2 and O3 had opposite temporal fluctuations, attributable to weather conditions and the accumulation of vehicular emissions. The effects of both desert dust storms and airborne particulate matter resulting from the Lebanon War in July 2006 are also discernible in the SRV plots. PMID:25150052

  14. Conformance Analysis of Clinical Pathway Using Electronic Health Record Data

    PubMed Central

    Cho, Minsu; Kim, Seok; Kim, Eunhye; Park, So Min; Kim, Kidong; Hwang, Hee

    2015-01-01

    Objectives The objective of this study was to confirm the conformance rate of the actual usage of the clinical pathway (CP) using Electronic Health Record (EHR) log data in a tertiary general university hospital to improve the CP by reflecting real-world care processes. Methods We analyzed the application and matching rates of clinicians' orders with predefined CP order sets based on data from 164 inpatients who received appendectomies out of all patients who were hospitalized from August 2013 to June 2014. We collected EHR log data on patient information, medication orders, operation performed, diagnosis, transfer, and CP order sets. The data were statistically analyzed. Results The average value of the actual application rate of the prescribed CP order ranged from 0.75 to 0.89. The application rate decreased when the order date was factored in along with the order code and type. Among CP pre-operation, intra-operation, post-operation, routine, and discharge orders, orders pertaining to operations had higher application rates than other types of orders. Routine orders and discharge orders had lower application rates. Conclusions This analysis of the application and matching rates of CP orders suggests that it is possible to improve these rates by updating the existing CP order sets for routine discharge orders to reflect data-driven evidence. This study shows that it is possible to improve the application and matching rates of the CP using EHR log data. However, further research should be performed to analyze the effects of these rates on care outcomes. PMID:26279952

  15. Tools for visualization and analysis of molecular networks, pathways, and -omics data

    PubMed Central

    Villaveces, Jose M; Koti, Prasanna; Habermann, Bianca H

    2015-01-01

    Biological pathways have become the standard way to represent the coordinated reactions and actions of a series of molecules in a cell. A series of interconnected pathways is referred to as a biological network, which denotes a more holistic view on the entanglement of cellular reactions. Biological pathways and networks are not only an appropriate approach to visualize molecular reactions. They have also become one leading method in -omics data analysis and visualization. Here, we review a set of pathway and network visualization and analysis methods and take a look at potential future developments in the field. PMID:26082651

  16. 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.

  17. Analysis of electrolyte level change in a lithium air battery

    NASA Astrophysics Data System (ADS)

    Huang, Jing; Faghri, Amir

    2016-03-01

    A two-dimensional physical model that employs the deformed mesh method to track the electrolyte level in a Li-air coin cell battery is presented and used to investigate the effects of electrolyte level drop during cell discharge. The electrolyte level drop is caused by solid phase volume decrease and electrolyte solvent evaporation. Simulation results show that by neglecting the drop in electrolyte level, a Li-air battery model would under-estimate cell discharge capacity by as much as 22.5% in the parameter range studied. This counter-intuitive result is explained by an in-depth analysis of simulation results. A more realistic prediction of Li2O2 deposit distribution is obtained, with the peak value of Li2O2 volume fraction in the middle of the cathode instead of on the top surface, as predicted by previous studies. The interaction between the battery and its surroundings is considered by incorporating the air chamber into the computation domain. The diffusion of solvent vapor and oxygen in this chamber is included. For batteries using volatile solvents such as DMF, increasing the air chamber radius from 5 cm to 15 cm would result in a 72% increase of discharge capacity at the cost of losing a large amount of electrolyte.

  18. 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.

  19. 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.

  20. Persistence analysis of daily mean air temperature variation in Georgia

    NASA Astrophysics Data System (ADS)

    Matcharashvili, Teimuraz; Chelidze, Tamaz; Zhukova, Natalia; Mepharidze, Ekaterine; Sborshchikov, Alexander

    2010-05-01

    Extrapolation of observed linear trends is common practice in climate change researches on different scales. In this respect it is important, that though global warming is well established, the question of persistence of trends on regional scales remain controversial. Indeed, climate change for specific region and time by definition includes more than the simple average of weather conditions. Either random events or long-term changes, or more often combinations of them, can bring about significant swings in a variety of climate indicators from one time period to the next. Therefore in order to achieve further understanding of dynamics of climate change the character of stable peculiarities of analyzed dynamics should be investigated. Analysis of the character of long range correlations in climatological time series or peculiarities of their inherent memory is motivated exactly by this goal. Such analysis carried out on a different scales may help to understand spatial and temporal features of regional climate change. In present work the problem of persistence of observed trends in air temperature time series in Georgia was investigated. Longest available mean daily temperature time series of Tbilisi (1890-2008) were analyzed. Time series on shorter time scales of five stations in the West and East Georgia also were considered as well as monthly mean temperature time series of five stations. Additionally, temporally and spatially averaged daily and monthly mean air temperature time series were analyzed. Extent of persistence in mentioned time series were evaluated using R/S analysis calculation. Detrended and Multifractal Detrended Fluctuation Analysis as well as multi scaling analysis based on CWT have been used. Our results indicate that variation of daily or monthly mean temperatures reveals clear antipersistence on whole available time scale. It seems that antipersistence on global scale is general characteristics of mean air temperature variation and is not

  1. PATHWAY-BASED ANALYSIS FOR GENOME-WIDE ASSOCIATION STUDIES USING SUPERVISED PRINCIPAL COMPONENTS

    PubMed Central

    Chen, Xi; Wang, Lily; Hu, Bo; Guo, Mingsheng; Barnard, John; Zhu, Xiaofeng

    2012-01-01

    Many complex diseases are influenced by genetic variations in multiple genes, each with only a small marginal effect on disease susceptibility. Pathway analysis, which identifies biological pathways associated with disease outcome, has become increasingly popular for genome-wide association studies (GWAS). In addition to combining weak signals from a number of SNPs in the same pathway, results from pathway analysis also shed light on the biological processes underlying disease. We propose a new pathway-based analysis method for GWAS, the supervised principal component analysis (SPCA) model. In the proposed SPCA model, a selected subset of SNPs most associated with disease outcome is used to estimate the latent variable for a pathway. The estimated latent variable for each pathway is an optimal linear combination of a selected subset of SNPs; therefore, the proposed SPCA model provides the ability to borrow strength across the SNPs in a pathway. In addition to identifying pathways associated with disease outcome, SPCA also carries out additional within-category selection to identify the most important SNPs within each gene set. The proposed model operates in a well-established statistical framework and can handle design information such as covariate adjustment and matching information in GWAS. We compare the proposed method with currently available methods using data with realistic linkage disequilibrium structures and we illustrate the SPCA method using the Wellcome Trust Case-Control Consortium Crohn Disease (CD) dataset. PMID:20842628

  2. Analysis of Heme Biosynthetic Pathways in a Recombinant Escherichia coli.

    PubMed

    Pranawidjaja, Stephanie; Choi, Su-In; Lay, Bibiana W; Kim, Pil

    2015-06-01

    Bacterial heme was produced from a genetic-engineered Escherichia coli via the porphyrin pathway and it was useful as an iron resource for animal feed. The amount of the E. colisynthesized heme, however, was only few milligrams in a culture broth and it was not enough for industrial applications. To analyze heme biosynthetic pathways, an engineered E. coli artificially overexpressing ALA synthase (hemA from Rhodobacter sphaeroides) and pantothenate kinase (coaA gene from self geneome) was constructed as a bacterial heme-producing strain, and both the transcription levels of pathway genes and the intermediates concentrations were determined from batch and continuous cultures. Transcription levels of the pathway genes were not significantly changed among the tested conditions. Intracellular intermediate concentrations indicated that aminolevulinic acid (ALA) and coenzyme A (CoA) were enhanced by the hemA-coaA co-expression. Intracellular coproporphyrinogen I and protoporphyrin IX accumulation suggested that the bottleneck steps in the heme biosynthetic pathway could be the spontaneous conversion of HMB to coproporphyrinogen I and the limited conversion of protoporphyrin IX to heme, respectively. A strategy to increase the conversion of ALA to heme is discussed based on the results. PMID:25537720

  3. 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.

  4. 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

  5. Gene expression analysis of aberrant signaling pathways in meningiomas

    PubMed Central

    TORRES-MARTÍN, MIGUEL; MARTINEZ-GLEZ, VICTOR; PEÑA-GRANERO, CAROLINA; ISLA, ALBERTO; LASSALETTA, LUIS; DE CAMPOS, JOSE M.; PINTO, GIOVANNY R.; BURBANO, ROMMEL R.; MELÉNDEZ, BÁRBARA; CASTRESANA, JAVIER S.; REY, JUAN A.

    2013-01-01

    Examining aberrant pathway alterations is one method for understanding the abnormal signals that are involved in tumorigenesis and tumor progression. In the present study, expression arrays were performed on tumor-related genes in meningiomas. The GE Array Q Series HS-006 was used to determine the expression levels of 96 genes that corresponded to six primary biological regulatory pathways in a series of 42 meningiomas, including 32 grade I, four recurrent grade I and six grade II tumors, in addition to three normal tissue controls. Results showed that 25 genes that were primarily associated with apoptosis and angiogenesis functions were downregulated and 13 genes frequently involving DNA damage repair functions were upregulated. In addition to the inactivation of the neurofibromin gene, NF2, which is considered to be an early step in tumorigenesis, variations of other biological regulatory pathways may play a significant role in the development of meningioma. PMID:23946817

  6. Gene expression analysis of aberrant signaling pathways in meningiomas.

    PubMed

    Torres-Martín, Miguel; Martinez-Glez, Victor; Peña-Granero, Carolina; Isla, Alberto; Lassaletta, Luis; DE Campos, Jose M; Pinto, Giovanny R; Burbano, Rommel R; Meléndez, Bárbara; Castresana, Javier S; Rey, Juan A

    2013-07-01

    Examining aberrant pathway alterations is one method for understanding the abnormal signals that are involved in tumorigenesis and tumor progression. In the present study, expression arrays were performed on tumor-related genes in meningiomas. The GE Array Q Series HS-006 was used to determine the expression levels of 96 genes that corresponded to six primary biological regulatory pathways in a series of 42 meningiomas, including 32 grade I, four recurrent grade I and six grade II tumors, in addition to three normal tissue controls. Results showed that 25 genes that were primarily associated with apoptosis and angiogenesis functions were downregulated and 13 genes frequently involving DNA damage repair functions were upregulated. In addition to the inactivation of the neurofibromin gene, NF2, which is considered to be an early step in tumorigenesis, variations of other biological regulatory pathways may play a significant role in the development of meningioma. PMID:23946817

  7. Systematic Analysis of the Associations between Adverse Drug Reactions and Pathways

    PubMed Central

    Chen, Xiaowen; Wang, Yanqiu; Wang, Pingping; Lian, Baofeng; Li, Chunquan; Wang, Jing; Li, Xia; Jiang, Wei

    2015-01-01

    Adverse drug reactions (ADRs) are responsible for drug candidate failure during clinical trials. It is crucial to investigate biological pathways contributing to ADRs. Here, we applied a large-scale analysis to identify overrepresented ADR-pathway combinations through merging clinical phenotypic data, biological pathway data, and drug-target relations. Evaluation was performed by scientific literature review and defining a pathway-based ADR-ADR similarity measure. The results showed that our method is efficient for finding the associations between ADRs and pathways. To more systematically understand the mechanisms of ADRs, we constructed an ADR-pathway network and an ADR-ADR network. Through network analysis on biology and pharmacology, it was found that frequent ADRs were associated with more pathways than infrequent and rare ADRs. Moreover, environmental information processing pathways contributed most to the observed ADRs. Integrating the system organ class of ADRs, we found that most classes tended to interact with other classes instead of themselves. ADR classes were distributed promiscuously in all the ADR cliques. These results reflected that drug perturbation to a certain pathway can cause changes in multiple organs, rather than in one specific organ. Our work not only provides a global view of the associations between ADRs and pathways, but also is helpful to understand the mechanisms of ADRs. PMID:26495310

  8. Modeling the optimal central carbon metabolic pathways under feedback inhibition using flux balance analysis.

    PubMed

    De, Rajat K; Tomar, Namrata

    2012-12-01

    Metabolism is a complex process for energy production for cellular activity. It consists of a cascade of reactions that form a highly branched network in which the product of one reaction is the reactant of the next reaction. Metabolic pathways efficiently produce maximal amount of biomass while maintaining a steady-state behavior. The steady-state activity of such biochemical pathways necessarily incorporates feedback inhibition of the enzymes. This observation motivates us to incorporate feedback inhibition for modeling the optimal activity of metabolic pathways using flux balance analysis (FBA). We demonstrate the effectiveness of the methodology on a synthetic pathway with and without feedback inhibition. Similarly, for the first time, the Central Carbon Metabolic (CCM) pathways of Saccharomyces cerevisiae and Homo sapiens have been modeled and compared based on the above understanding. The optimal pathway, which maximizes the amount of the target product(s), is selected from all those obtained by the proposed method. For this, we have observed the concentration of the product inhibited enzymes of CCM pathway and its influence on its corresponding metabolite/substrate. We have also studied the concentration of the enzymes which are responsible for the synthesis of target products. We further hypothesize that an optimal pathway would opt for higher flux rate reactions. In light of these observations, we can say that an optimal pathway should have lower enzyme concentration and higher flux rates. Finally, we demonstrate the superiority of the proposed method by comparing it with the extreme pathway analysis. PMID:22913632

  9. Preliminary pathway analysis for YMP preclosure biosphere dose assessment

    SciTech Connect

    Wu, D.; Liu, N.; Tappen, J.J.; Tung, C.H.

    1998-05-13

    The preliminary preclosure biosphere dose assessment for the Yucca Mountain Project (YMP) involves the calculation of a radiation dose to a subsistence farmer living near the proposed Yucca Mountain repository. Eight radionuclides, H-3, Co-60, Kr-85, Sr-90, Ru-106, I-129, Cs-134, and Cs-137, are considered in this study. Radiation doses resulting from unit release rates of these radionuclides are analyzed. Total dose has been broken down into components that result from various exposure pathways. By using this approach, the most important pathways that deliver a radiation dose to a subsistence farmer can be clearly identified.

  10. A Two-Stage Random Forest-Based Pathway Analysis Method

    PubMed Central

    Chung, Ren-Hua; Chen, Ying-Erh

    2012-01-01

    Pathway analysis provides a powerful approach for identifying the joint effect of genes grouped into biologically-based pathways on disease. Pathway analysis is also an attractive approach for a secondary analysis of genome-wide association study (GWAS) data that may still yield new results from these valuable datasets. Most of the current pathway analysis methods focused on testing the cumulative main effects of genes in a pathway. However, for complex diseases, gene-gene interactions are expected to play a critical role in disease etiology. We extended a random forest-based method for pathway analysis by incorporating a two-stage design. We used simulations to verify that the proposed method has the correct type I error rates. We also used simulations to show that the method is more powerful than the original random forest-based pathway approach and the set-based test implemented in PLINK in the presence of gene-gene interactions. Finally, we applied the method to a breast cancer GWAS dataset and a lung cancer GWAS dataset and interesting pathways were identified that have implications for breast and lung cancers. PMID:22586488

  11. Spectroscopic analysis of femtosecond laser plasma filament in air

    NASA Astrophysics Data System (ADS)

    Bernhardt, J.; Liu, W.; Théberge, F.; Xu, H. L.; Daigle, J. F.; Châteauneuf, M.; Dubois, J.; Chin, S. L.

    2008-03-01

    We report a spectroscopic analysis of a filament generated by a femtosecond laser pulse in air. In the filament spectra, the characteristic Stark broadened atomic oxygen triplet centered at 777.4 nm has been observed. The measured electron impact Stark broadening parameter of the triplet is larger than the theoretical value by Griem [H.R. Griem, Plasma Spectroscopy, McGraw Hill, New York, 1964] by a factor 6.7 . Using the experimental value 0.0166nm , the plasma densities derived from Stark broadening agree well with those most recently obtained from Théberge et al.'s measurement of the nitrogen fluorescence calibrated by longitudinal diffraction [F. Théberge, W. Liu, P.T. Simard, A. Becker, S. L. Chin, Phys. Rev. E 74 (2006) 036406]. However, the Stark broadening approach is much simpler and can be used to non-invasively measure the filament plasma density distribution in air under different propagation conditions.

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

    PubMed

    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

  13. Flux analysis of cholesterol biosynthesis in vivo reveals multiple tissue and cell-type specific pathways

    PubMed Central

    Mitsche, Matthew A; McDonald, Jeffrey G; Hobbs, Helen H; Cohen, Jonathan C

    2015-01-01

    Two parallel pathways produce cholesterol: the Bloch and Kandutsch-Russell pathways. Here we used stable isotope labeling and isotopomer analysis to trace sterol flux through the two pathways in mice. Surprisingly, no tissue used the canonical K–R pathway. Rather, a hybrid pathway was identified that we call the modified K–R (MK–R) pathway. Proportional flux through the Bloch pathway varied from 8% in preputial gland to 97% in testes, and the tissue-specificity observed in vivo was retained in cultured cells. The distribution of sterol isotopomers in plasma mirrored that of liver. Sterol depletion in cultured cells increased flux through the Bloch pathway, whereas overexpression of 24-dehydrocholesterol reductase (DHCR24) enhanced usage of the MK–R pathway. Thus, relative use of the Bloch and MK–R pathways is highly variable, tissue-specific, flux dependent, and epigenetically fixed. Maintenance of two interdigitated pathways permits production of diverse bioactive sterols that can be regulated independently of cholesterol. DOI: http://dx.doi.org/10.7554/eLife.07999.001 PMID:26114596

  14. 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

  15. Seismic analysis of reactor exhaust air filter compartment

    SciTech Connect

    Gong, Chung; Funderburk, E.L.; Jerrell, J.W.

    1990-09-24

    The Filter Compartment (FC) in this analysis is a generic reactor airborne activity confinement filter compartment which possesses all the essential physical and mechanical properties of the Savannah River Site (SRS) confinement filters of Reactor Buildings K, L, and P. The filters belong to the Airborne Activity Confinement System (AACS). These filters absorb a significant amount of radioactive effluents from the exhausting air. The seismic excitation is input indirectly from the output of the seismic analysis of the 105 exhaust stack building in the form of floor response spectra. However, the 105 exhaust stack building was analyzed for seismic motions defined by free-field ground response spectra with a ZPA (Zero Period Acceleration) of 0.2G for all three orthogonal components of ground motion and a shape consistent with USNRC Regulatory Guide 1.60. Based upon equivalent dynamic analysis of the FC, DuPont engineers suggested modifications on the existing FC with heavy I-section beams [1]. The scope of this ``phase I`` analysis, as requested by Seismic Engineering [2], is to carry out a ``scoping analysis`` of Frequency Analysis and Response Spectrum Analysis of the FC with DuPont suggested conceptual modifications. Our suggestion was that the existing FC without conceptual modifications be analyzed first. However, the schedule urgency of the project and with guidance from the previous seismic analysis established the priority to perform the analysis for the FC with modifications in the ``phase I`` calculations.

  16. Seismic analysis of reactor exhaust air filter compartment

    SciTech Connect

    Gong, Chung; Funderburk, E.L.; Jerrell, J.W.

    1990-09-24

    The Filter Compartment (FC) in this analysis is a generic reactor airborne activity confinement filter compartment which possesses all the essential physical and mechanical properties of the Savannah River Site (SRS) confinement filters of Reactor Buildings K, L, and P. The filters belong to the Airborne Activity Confinement System (AACS). These filters absorb a significant amount of radioactive effluents from the exhausting air. The seismic excitation is input indirectly from the output of the seismic analysis of the 105 exhaust stack building in the form of floor response spectra. However, the 105 exhaust stack building was analyzed for seismic motions defined by free-field ground response spectra with a ZPA (Zero Period Acceleration) of 0.2G for all three orthogonal components of ground motion and a shape consistent with USNRC Regulatory Guide 1.60. Based upon equivalent dynamic analysis of the FC, DuPont engineers suggested modifications on the existing FC with heavy I-section beams (1). The scope of this phase I'' analysis, as requested by Seismic Engineering (2), is to carry out a scoping analysis'' of Frequency Analysis and Response Spectrum Analysis of the FC with DuPont suggested conceptual modifications. Our suggestion was that the existing FC without conceptual modifications be analyzed first. However, the schedule urgency of the project and with guidance from the previous seismic analysis established the priority to perform the analysis for the FC with modifications in the phase I'' calculations.

  17. 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.

  18. [Analysis of the Basic Stress Pathway Above Acetabular Dome].

    PubMed

    Nie, Yong; Ma, Jun; Haung, Qiang; Hu, Qinsheng; Shi, Xiaojun; Pei, Fuxing

    2015-08-01

    The basic stress pathway above the acetabular dome is important for the maintenance of implant stability in acetabular reconstruction of total hip arthroplasty (THA). The purpose of this study was to describe the basic stress pathway to provide evidence for clinical acetabular reconstruction guidance of THA. A subject-specific finite element (FE) model was developed from CT data to generate 3 normal hip models and a convergence study was conducted to determine the number of pelvic trabecular bone material properties using 5 material assignment plans. In addition, in the range of 0 to 20 mm above the acetabular dome, the models were sectioned and the stress pathway was defined as two parts, i.e., 3D, trabecular bone stress distribution and quantified cortical bone stress level. The results showed that using 100 materials to define the material property of pelvic trabecular bone could assure both the accuracy and efficiency of the FE model. Under the same body weight condition, the 3D trabecular bone stress distributions above the acetabular dome were consistent, and especially the quantified cortical bone stress levels were all above 20 MPa and showed no statistically significant difference (P>0.05). Therefore, defining the basic stress pathway above the acetabular dome under certain body weight condition contributes to design accurate preoperative plan for acetabular reconstruction, thus helping restore the normal hip biomechanics and preserve the stability of the implants. PMID:26710451

  19. Relative Humidity and its Effect on Sampling and Analysis of Agricultural Odorants in Air

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Source and ambient air sampling techniques used in agricultural air quality studies are seldom validated for the variability in the air matrix (temperature, dust levels, and relative humidity). In particular, relative humidity (RH) affects both field sampling and analysis of air samples. The objec...

  20. Systems analysis of gene ontology and biological pathways involved in post-myocardial infarction responses

    PubMed Central

    2015-01-01

    Background Pathway analysis has been widely used to gain insight into essential mechanisms of the response to myocardial infarction (MI). Currently, there exist multiple pathway databases that organize molecular datasets and manually curate pathway maps for biological interpretation at varying forms of organization. However, inconsistencies among different databases in pathway descriptions, frequently due to conflicting results in the literature, can generate incorrect interpretations. Furthermore, although pathway analysis software provides detailed images of interactions among molecules, it does not exhibit how pathways interact with one another or with other biological processes under specific conditions. Methods We propose a novel method to standardize descriptions of enriched pathways for a set of genes/proteins using Gene Ontology terms. We used this method to examine the relationships among pathways and biological processes for a set of condition-specific genes/proteins, represented as a functional biological pathway-process network. We applied this algorithm to a set of 613 MI-specific proteins we previously identified. Results A total of 96 pathways from Biocarta, KEGG, and Reactome, and 448 Gene Ontology Biological Processes were enriched with these 613 proteins. The pathways were represented as Boolean functions of biological processes, delivering an interactive scheme to organize enriched information with an emphasis on involvement of biological processes in pathways. We extracted a network focusing on MI to demonstrate that tyrosine phosphorylation of Signal Transducer and Activator of Transcription (STAT) protein, positive regulation of collagen metabolic process, coagulation, and positive/negative regulation of blood coagulation have immediate impacts on the MI response. Conclusions Our method organized biological processes and pathways in an unbiased approach to provide an intuitive way to identify biological properties of pathways under specific

  1. 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

  2. Review of maritime transportation air emission pollution and policy analysis

    NASA Astrophysics Data System (ADS)

    Wang, Haifeng; Liu, Dahai; Dai, Guilin

    2009-09-01

    The study of air emission in maritime transportation is new, and the recognition of its importance has been rising in the recent decade. The emissions of CO2, SO2, NO2 and particulate matters from maritime transportation have contributed to climate change and environmental degradation. Scientifically, analysts still have controversies regarding how to calculate the emissions and how to choose the baseline and methodologies. Three methods are generally used, namely the ‘bottom up’ approach, the ‘top down’ approach and the STEEM, which produce very different results, leading to various papers with great uncertainties. This, in turn, results in great difficulties to policy makers who attempt to regulate the emissions. A recent technique, the STEEM, is intended to combine the former two methods to reduce their drawbacks. However, the regulations based on its results may increase the costs of shipping companies and cause the competitiveness of the port states and coastal states. Quite a few papers have focused on this area and provided another fresh perspective for the air emission to be incorporated in maritime transportation regulations; these facts deserve more attention. This paper is to review the literature on the debates over air emission calculation, with particular attention given to the STEEM and the refined estimation methods. It also reviews related literature on the economic analysis of maritime transportation emission regulations, and provides an insight into such analysis. At the end of this paper, based on a review and analysis of previous literature, we conclude with the policy indications in the future and work that should be done. As the related regulations in maritime transportation emissions are still at their beginning stage in China, this paper provides specific suggestions on how China should regulate emissions in the maritime transportation sector.

  3. 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...

  4. 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.

  5. Cyclic stress analysis of an air-cooled turbine vane

    NASA Technical Reports Server (NTRS)

    Kaufman, A.; Gauntner, D. J.; Gauntner, J. W.

    1975-01-01

    The effects of gas pressure level, coolant temperature, and coolant flow rate on the stress-strain history and life of an air-cooled vane were analyzed using measured and calculated transient metal temperatures and a turbine blade stress analysis program. Predicted failure locations were compared to results from cyclic tests in a static cascade and engine. The results indicate that a high gas pressure was detrimental, a high coolant flow rate somewhat beneficial, and a low coolant temperature the most beneficial to vane life.

  6. [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. PMID:23234001

  7. Asphaltene Erosion Process in Air Plasma: Emission Spectroscopy and Surface Analysis for Air-Plasma Reactions

    NASA Astrophysics Data System (ADS)

    Martinez, H.; Flores, O.; C. Poveda, J.; Campillo, B.

    2012-04-01

    Optical emission spectroscopy (OES) was applied for plasma characterization during the erosion of asphaltene substrates. An amount of 100 mg of asphaltene was carefully applied to an electrode and exposed to air-plasma glow discharge at a pressure of 1.0 Torr. The plasma was generated in a stainless steel discharge chamber by an ac generator at a frequency of 60 Hz, output power of 50 W and a gas flow rate of 1.8 L/min. The electron temperature and ion density were estimated to be 2.15±0.11 eV and (1.24±0.05) × 1016 m-3, respectively, using a double Langmuir probe. OES was employed to observe the emission from the asphaltene exposed to air plasma. Both molecular band emission from N2, N+2, OH, CH, NH, O2 as well as CN, and atomic light emission from V and Hγ were observed and used to monitor the evolution of asphaltene erosion. The asphaltene erosion was analyzed with the aid of a scanning electron microscope (SEM) equipped with an energy dispersive X-ray (EDX) detector. The EDX analysis showed that the time evolution of elements C, O, S and V were similar; and the chemical composition of the exposed asphaltenes remained constant. Particle size evolution was measured, showing a maximum size of 2307 μm after 60 min. This behavior is most likely related to particle agglomeration as a function of time.

  8. 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...

  9. Perturbation Experiments: Approaches for Metabolic Pathway Analysis in Bioreactors.

    PubMed

    Weiner, Michael; Tröndle, Julia; Albermann, Christoph; Sprenger, Georg A; Weuster-Botz, Dirk

    2016-01-01

    In the last decades, targeted metabolic engineering of microbial cells has become one of the major tools in bioprocess design and optimization. For successful application, a detailed knowledge is necessary about the relevant metabolic pathways and their regulation inside the cells. Since in vitro experiments cannot display process conditions and behavior properly, process data about the cells' metabolic state have to be collected in vivo. For this purpose, special techniques and methods are necessary. Therefore, most techniques enabling in vivo characterization of metabolic pathways rely on perturbation experiments, which can be divided into dynamic and steady-state approaches. To avoid any process disturbance, approaches which enable perturbation of cell metabolism in parallel to the continuing production process are reasonable. Furthermore, the fast dynamics of microbial production processes amplifies the need of parallelized data generation. These points motivate the development of a parallelized approach for multiple metabolic perturbation experiments outside the operating production reactor. An appropriate approach for in vivo characterization of metabolic pathways is presented and applied exemplarily to a microbial L-phenylalanine production process on a 15 L-scale. PMID:25981857

  10. Analysis of oxyluciferin photoluminescence pathways in aqueous solutions.

    PubMed

    Hiyama, Miyabi; Mochizuki, Toshimitsu; Akiyama, Hidefumi; Koga, Nobuaki

    2015-01-01

    We evaluated the pK(a) values of oxyluciferin and its conjugate acids and bases theoretically with the help of experimental correction values, from which free energies for the first excited and the ground states of all the species were estimated. On the basis of these results, we calculated pH-dependent absorption spectra, where the relative absorption intensities of various species strongly depend on photoexcitation energy, and we further analyzed the photoluminescence pathways of oxyluciferin in aqueous solutions with various pH. In the case of 350 nm photoexcitation, in particular, experiments have shown that dominant emission color is green and it attenuates with pH decreasing, while blue (3 < pH < 8) and red (pH < 3) emissions appear. Our present results clarify the pathways of these photoluminescence depending on the pH values and thus should be useful in further analyses of photoluminescence pathways for other photoexcitation wavelength in comparison with experiments. PMID:25334091

  11. Integrative pathway analysis of genome-wide association studies and gene expression data in prostate cancer

    PubMed Central

    2012-01-01

    Background Pathway analysis of large-scale omics data assists us with the examination of the cumulative effects of multiple functionally related genes, which are difficult to detect using the traditional single gene/marker analysis. So far, most of the genomic studies have been conducted in a single domain, e.g., by genome-wide association studies (GWAS) or microarray gene expression investigation. A combined analysis of disease susceptibility genes across multiple platforms at the pathway level is an urgent need because it can reveal more reliable and more biologically important information. Results We performed an integrative pathway analysis of a GWAS dataset and a microarray gene expression dataset in prostate cancer. We obtained a comprehensive pathway annotation set from knowledge-based public resources, including KEGG pathways and the prostate cancer candidate gene set, and gene sets specifically defined based on cross-platform information. By leveraging on this pathway collection, we first searched for significant pathways in the GWAS dataset using four methods, which represent two broad groups of pathway analysis approaches. The significant pathways identified by each method varied greatly, but the results were more consistent within each method group than between groups. Next, we conducted a gene set enrichment analysis of the microarray gene expression data and found 13 pathways with cross-platform evidence, including "Fc gamma R-mediated phagocytosis" (PGWAS = 0.003, Pexpr < 0.001, and Pcombined = 6.18 × 10-8), "regulation of actin cytoskeleton" (PGWAS = 0.003, Pexpr = 0.009, and Pcombined = 3.34 × 10-4), and "Jak-STAT signaling pathway" (PGWAS = 0.001, Pexpr = 0.084, and Pcombined = 8.79 × 10-4). Conclusions Our results provide evidence at both the genetic variation and expression levels that several key pathways might have been involved in the pathological development of prostate cancer. Our framework that employs gene expression data to facilitate

  12. 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

  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. A cross-study gene set enrichment analysis identifies critical pathways in endometriosis

    PubMed Central

    Zhao, Hongbo; Wang, Qishan; Bai, Chunyan; He, Kan; Pan, Yuchun

    2009-01-01

    Background Endometriosis is an enigmatic disease. Gene expression profiling of endometriosis has been used in several studies, but few studies went further to classify subtypes of endometriosis based on expression patterns and to identify possible pathways involved in endometriosis. Some of the observed pathways are more inconsistent between the studies, and these candidate pathways presumably only represent a fraction of the pathways involved in endometriosis. Methods We applied a standardised microarray preprocessing and gene set enrichment analysis to six independent studies, and demonstrated increased concordance between these gene datasets. Results We find 16 up-regulated and 19 down-regulated pathways common in ovarian endometriosis data sets, 22 up-regulated and one down-regulated pathway common in peritoneal endometriosis data sets. Among them, 12 up-regulated and 1 down-regulated were found consistent between ovarian and peritoneal endometriosis. The main canonical pathways identified are related to immunological and inflammatory disease. Early secretory phase has the most over-represented pathways in the three uterine cycle phases. There are no overlapping significant pathways between the dataset from human endometrial endothelial cells and the datasets from ovarian endometriosis which used whole tissues. Conclusion The study of complex diseases through pathway analysis is able to highlight genes weakly connected to the phenotype which may be difficult to detect by using classical univariate statistics. By standardised microarray preprocessing and GSEA, we have increased the concordance in identifying many biological mechanisms involved in endometriosis. The identified gene pathways will shed light on the understanding of endometriosis and promote the development of novel therapies. PMID:19735579

  15. 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.

  16. 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

    2015-01-01

    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. PMID:26662407

  17. Genome-wide pathway analysis in attention-deficit/hyperactivity disorder.

    PubMed

    Lee, Young Ho; Song, Gwan Gyu

    2014-08-01

    This study aimed to (1) to identify candidate single-nucleotide polymorphisms (SNPs) and mechanisms of attention-deficit/hyperactivity disorder (ADHD) and (2) to generate SNP-to-gene-to-pathway hypotheses. An ADHD genome-wide association study (GWAS) dataset that included 428,074 SNPs in 924 trios (2,758 individuals) of European descent was used in this study. The Identify candidate Causal SNPs and Pathways (ICSNPathway) analysis was applied to the GWAS dataset. ICSNPathway analysis identified 11 candidate SNPs, 6 genes, and 6 pathways, which provided 6 hypothetical biological mechanisms. The strongest hypothetical biological mechanism was that rs2532502 alters the role of CD27 in the context of the pathways of positive regulation of nucleocytoplasmic transport [nominal p < 0.001; false discovery rate (FDR) = 0.028]. The second strongest mechanism was the rs1820204, rs1052571, rs1052576 → CASP9 → mitochondrial pathway (nominal p < 0.001; FDR = 0.032). The third mechanism was the rs1801516 → ATM → CD25 pathway (nominal p < 0.001; FDR = 0.034). By applying the ICSNPathway analysis to the ADHD GWAS data, 11 candidate SNPs, 6 genes that included CD27, CASP9, ATM, CD12orf65, OXER1, and ACRY, and 6 pathways were identified that may contribute to ADHD susceptibility. PMID:24531918

  18. 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.

  19. Modeling and Analysis of Aluminum/Air Fuel Cell

    NASA Astrophysics Data System (ADS)

    Leon, Armando J.

    The technical and scientific challenges to provide reliable sources energy for US and global economy are enormous tasks, and especially so when combined with strategic and recent economic concerns of the last five years. It is clear that as part of the mix of energy sources necessary to deal with these challenges, fuel cells technology will play critical or even a central role. The US Department of Energy, as well as a number of the national laboratories and academic institutions have been aware of the importance such technology for some time. Recently, car manufacturers, transportation experts, and even utilities are paying attention to this vital source of energy for the future. In this thesis, a review of the main fuel cell technologies is presented with the focus on the modeling, and control of one particular and promising fuel cell technology, aluminum air fuel cells. The basic principles of this fuel cell technology are presented. A major part of the study consists of a description of the electrochemistry of the process, modeling, and simulations of aluminum air FC using Matlab Simulink(TM). The controller design of the proposed model is also presented. In sequel, a power management unit is designed and analyzed as an alternative source of power. Thus, the system commutes between the fuel cell output and the alternative power source in order to fulfill a changing power load demand. Finally, a cost analysis and assessment of this technology for portable devices, conclusions and future recommendations are presented.

  20. 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.

  1. 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.

  2. Genetic variants and risk of esophageal squamous cell carcinoma: A GWAS-based pathway analysis

    PubMed Central

    Yang, Xi; Zhu, Hongcheng; Qin, Qin; Yang, Yuehua; Yang, Yan; Cheng, Hongyan; Sun, Xinchen

    2015-01-01

    This study was designed to identify candidate single-nucleotide polymorphisms (SNPs) that may affect the susceptibility to esophageal squamous cell carcinoma (ESCC) and elucidate their potential mechanisms to generate SNP-to-gene-to-pathway hypotheses. A genome-wide association study (GWAS) dataset for ESCC, which included 453,852 SNPs from 1898 ESCC patients and 2100 control subjects of Chinese population, was reviewed. The identify candidate causal SNPs and pathways (ICSNPathway) analysis identified seven candidate SNPs, five genes, and seven pathways, which together revealed seven hypothetical biological mechanisms. The three strongest hypothetical biological mechanisms were as follows: rs4135113 → TDG → BASE EXCISION REPAIR; rs1800450 → MBL2 → MONOSACCHARIDE BINDING; and rs3769823 → CASP8 → d4gdiPathway. The GWAS dataset was evaluated using the ICSNPathway, which showed seven candidate SNPs, five genes, and seven pathways that may contribute to the susceptibility of patients to ESCC. PMID:25431829

  3. Multivariate analysis comparing microbial air content of an air-conditioned building and a naturally ventilated building over one year

    NASA Astrophysics Data System (ADS)

    Parat, Sylvie; Perdrix, Alain; Fricker-Hidalgo, Hélène; Saude, Isabelle; Grillot, Renee; Baconnier, Pierre

    Heating, ventilation and air-conditioning (HVAC) may be responsible for the production and spread of airborne microorganisms in office buildings. In order to compare airborne microbiological flora in an air-conditioned building with that in a naturally ventilated building, eight sets of measurements were made over a 1-year period. Concurrently with other environmental measurements, air samples were collected in each building, from three offices and from the outdoor air, using the Andersen single-stage sampler. Three different media were used to culture fungi, staphylococci and mesophilic bacteria. Multivariate analysis revealed a group of offices more contaminated than others, and a marked seasonal variation in fungal concentrations. A comparison of mean levels of microorganisms measured in the two buildings showed that the air microbial content was significantly higher and more variable in the naturally ventilated building than in the air-conditioned building. Moreover, in the naturally ventilated building, the interior fungal content was strongly dependent on the outdoor content, while in the air-conditioned building fungal concentrations remained constant despite significant variations measured outside. This was confirmed by a statistical comparison of the correlation coefficients between indoor and outdoor concentrations. No difference was observed regarding gaseous pollutants and temperature, but relative humidity was significantly higher in the air-conditioned building. The effect of HVAC was to prevent the intake of outdoor particles and to dilute the indoor concentrations. These results are consistent with the presence of high-efficiency filters and a steam humidifier in the HVAC system under study.

  4. 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.

  5. A critical analysis of air shower structure functions and size spectrum measurements with the NBU air shower array

    NASA Technical Reports Server (NTRS)

    Chaudhuri, N.; Basak, D. K.

    1985-01-01

    A total of 11,000 showers in the size range 10 to the 4 to 10 to the 6 particles so far detected by the NBU air shower array has been analyzed using five different structure functions. A comparison of structure functions in terms: (1) of shower size; and (2) electron density at various core distances has been discussed to indicate the present status of structure functions in air shower analysis.

  6. [Detecting shared pathways linked to rheumatoid arthritis with other autoimmune diseases in a in silico analysis].

    PubMed

    Zheng, W-Y; Zheng, W-X; Hua, L

    2016-01-01

    Pathway-based analysis approach has exploded in use during the last several years. It is successful in recognizing additional biological insight of disease and finding groupings of risk genes that represent disease developing processes. Therefore, shared pathways, with pleiotropic effects, are important for understanding similar pathogenesis and indicating the common genetic origin of certain diseases. Here, we present a pathway analysis to reveal the potential disease associations between RA and three potential RA-related autoimmune diseases: psoriasis, diabetes mellitus, type 1 (T1D) and systemic lupus erythematosus (SLE). First, a comprehensive knowledge mining of public databases is performed to discover risk genes associated with RA, T1D, SLE and psoriasis; then by enrichment test of these genes, disease-related risk pathways are detected to recognize the pathways common for RA and three other diseases. Finally, the underlying disease associations are evaluated with the association rules mining method. In total, we identify multiple RA risk pathways with significant pleiotropic effects, the most unsurprising of which are the immunology related pathways. Meanwhile for the first time we highlight the involvement of the viral myocarditis pathway related to cardiovascular disease (CVD) in autoimmune diseases such as RA, psoriasis, T1D and SLE. Further Association rule mining results validate the strong association between RA and T1D and RA and SLE. It is clear that pleiotropy is a common property of pathways associated with disease traits. We provide novel pathway associations among RA and three autoimmune diseases. These results ascertain that there are shared genetic risk profiles that predispose individuals to autoimmune diseases. PMID:27414792

  7. Comparisons of seven algorithms for pathway analysis using the WTCCC Crohn's Disease dataset

    PubMed Central

    2011-01-01

    Background Though rooted in genomic expression studies, pathway analysis for genome-wide association studies (GWAS) has gained increasing popularity, since it has the potential to discover hidden disease pathogenic mechanisms by combining statistical methods with biological knowledge. Generally, algorithms or programs proposed recently can be categorized by different types of input data, null hypothesis or counts of analysis stages. Due to complexity caused by SNP, gene and pathway relationships, re-sampling strategies like permutation are always utilized to derive an empirical distribution for test statistics for evaluating the significance of candidate pathways. However, evaluation of these algorithms on real GWAS datasets and real biological pathway databases needs to be addressed before we apply them widely with confidence. Findings Two algorithms which use summary statistics from GWAS as input were implemented in KGG, a novel and user-friendly software tool for GWAS pathway analysis. Comparisons of these two algorithms as well as the other five selected algorithms were conducted by analyzing the WTCCC Crohn's Disease dataset utilizing the MsigDB canonical pathways. As a result of using permutation to obtain empirical p-value, most of these methods could control Type I error rate well, although some are conservative. However, the methods varied greatly in terms of power and running time, with the PLINK truncated set-based test being the most powerful and KGG being the fastest. Conclusions Raw data-based algorithms, such as those implemented in PLINK, are preferable for GWAS pathway analysis as long as computational capacity is available. It may be worthwhile to apply two or more pathway analysis algorithms on the same GWAS dataset, since the methods differ greatly in their outputs and might provide complementary findings for the studied complex disease. PMID:21981765

  8. 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. PMID:15704171

  9. A Comprehensive Analysis of AIRS Near Surface Air Temperature and Water Vapor Over Land and Tropical Ocean

    NASA Astrophysics Data System (ADS)

    Dang, H. V. T.; Lambrigtsen, B.; Manning, E. M.; Fetzer, E. J.; Wong, S.; Teixeira, J.

    2015-12-01

    Version 6 (V6) of the Atmospheric Infrared Sounder's (AIRS) combined infrared and microwave (IR+MW) retrieval of near surface air temperature (NSAT) and water vapor (NSWV) is validated over the United States with the densely populated MESONET data. MESONET data is a collection of surface/near surface meteorological data from many federal and state agencies. The ones used for this analysis are measured from instruments maintained by the National Weather Service (NWS), the Federal Aviation Administration (FAA), and the Interagency Remote Automatic Weather Stations (RAWS), resulting in a little more than four thousand locations throughout the US. Over the Tropical oceans, NSAT and NSWV are compared to a network of moored buoys from the Tropical Atmosphere Ocean/Triangle Trans-Ocean Buoy Network (TAO/TRITON), and the Pilot Research Moored Array in the Tropical Atlantic (PIRATA). With the analysis of AIRS surface and near surface products over ocean, we glean information on how retrieval of NSAT and NSWV over land can be improved and why it needs some adjustments. We also compare AIRS initial guess of near surface products that are trained on fifty days of ECMWF along with AIRS calibrated radiances, to ECMWF analysis data. The comparison is done to show the differing characteristics of AIRS initial guesses from ECMWF.

  10. 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.

  11. Measurements and analysis of air quality in Islamabad, Pakistan

    NASA Astrophysics Data System (ADS)

    Rasheed, Anjum; Aneja, Viney P.; Aiyyer, Anantha; Rafique, Uzaira

    2014-06-01

    Ambient air quality of Islamabad, Pakistan, reveals that annual average mass concentration of particulate matter (PM2.5) (˜45 to ˜95 µg m-3) and nitric oxide (NO) (˜41 to ˜120 µg m-3) exceeds the Pakistan's National Environmental Quality Standards (NEQS). The annual ozone (O3) concentration is within the permissible limits; however, some of the hourly concentration exceeds the NEQS mostly during the summer months. Correlation studies suggest that carbon monoxide (CO) has a significant (p-value ≤ 0.01) positive correlation with NO and NOy'; whereas, with O3, a significant (p-value ≤ 0.01) negative correlation is observed. The regression analysis estimates the background CO concentration to be ˜300 to ˜600 ppbv in Islamabad. The higher ratio of CO/NO (˜10) suggests that mobile sources are the major contributor to NO concentration. On the other hand, the ratio analysis of sulfur dioxide (SO2)/NO for Islamabad (˜0.011) indicates that the point sources are contributing to SO2 in the city. NO and SO2 correlation indicates contribution of direct sulfur emission sources. Ratios of [CO] to [NO] and [SO2] to [NO], based on ambient air quality measurements, provide a test for emission inventories. The ratios of these pollutants in the available Islamabad emission inventories are consistent with ambient values for these pollutants. The correlation of PM2.5 and NO suggests that a fraction of secondary PM2.5 is produced by chemical conversion of NO into nitrates. The regional background O3 concentration for Islamabad has been determined to be ˜31 ppbv. This study suggests that there is an increase in O3 concentration with increases in photochemical conversion of NO to reservoir NOy' species.

  12. 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

  13. A Bayesian Approach to Pathway Analysis by Integrating Gene–Gene Functional Directions and Microarray Data

    PubMed Central

    Zhao, Yifang; Chen, Ming-Hui; Pei, Baikang; Rowe, David; Shin, Dong-Guk; Xie, Wangang; Yu, Fang; Kuo, Lynn

    2012-01-01

    Many statistical methods have been developed to screen for differentially expressed genes associated with specific phenotypes in the microarray data. However, it remains a major challenge to synthesize the observed expression patterns with abundant biological knowledge for more complete understanding of the biological functions among genes. Various methods including clustering analysis on genes, neural network, Bayesian network and pathway analysis have been developed toward this goal. In most of these procedures, the activation and inhibition relationships among genes have hardly been utilized in the modeling steps. We propose two novel Bayesian models to integrate the microarray data with the putative pathway structures obtained from the KEGG database and the directional gene–gene interactions in the medical literature. We define the symmetric Kullback–Leibler divergence of a pathway, and use it to identify the pathway(s) most supported by the microarray data. Monte Carlo Markov Chain sampling algorithm is given for posterior computation in the hierarchical model. The proposed method is shown to select the most supported pathway in an illustrative example. Finally, we apply the methodology to a real microarray data set to understand the gene expression profile of osteoblast lineage at defined stages of differentiation. We observe that our method correctly identifies the pathways that are reported to play essential roles in modulating bone mass. PMID:23482678

  14. 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.

  15. timeClip: pathway analysis for time course data without replicates

    PubMed Central

    2014-01-01

    Background Time-course gene expression experiments are useful tools for exploring biological processes. In this type of experiments, gene expression changes are monitored along time. Unfortunately, replication of time series is still costly and usually long time course do not have replicates. Many approaches have been proposed to deal with this data structure, but none of them in the field of pathway analysis. Pathway analyses have acquired great relevance for helping the interpretation of gene expression data. Several methods have been proposed to this aim: from the classical enrichment to the more complex topological analysis that gains power from the topology of the pathway. None of them were devised to identify temporal variations in time course data. Results Here we present timeClip, a topology based pathway analysis specifically tailored to long time series without replicates. timeClip combines dimension reduction techniques and graph decomposition theory to explore and identify the portion of pathways that is most time-dependent. In the first step, timeClip selects the time-dependent pathways; in the second step, the most time dependent portions of these pathways are highlighted. We used timeClip on simulated data and on a benchmark dataset regarding mouse muscle regeneration model. Our approach shows good performance on different simulated settings. On the real dataset, we identify 76 time-dependent pathways, most of which known to be involved in the regeneration process. Focusing on the 'mTOR signaling pathway' we highlight the timing of key processes of the muscle regeneration: from the early pathway activation through growth factor signals to the late burst of protein production needed for the fiber regeneration. Conclusions timeClip represents a new improvement in the field of time-dependent pathway analysis. It allows to isolate and dissect pathways characterized by time-dependent components. Furthermore, using timeClip on a mouse muscle regeneration

  16. 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...

  17. 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. PMID:25660806

  18. 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

  19. GAS CHROMATOGRAPHY/MATRIX ISOLATION - INFRARED SPECTROMETRY FOR AIR SAMPLE ANALYSIS

    EPA Science Inventory

    This report describes the application of gas chromatography/matrix- solation infrared (GC/MI-IR) spectrometry to the analysIs of environmental air sample extracts. Samples that were analyzed include extracts from woodsmoke-impacted air, XAD-2 blanks, indoor air, and carpet sample...

  20. 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. PMID:26704307

  1. Identification of Major Signaling Pathways in Prion Disease Progression Using Network Analysis.

    PubMed

    Newaz, Khalique; Sriram, K; Bera, Debajyoti

    2015-01-01

    Prion diseases are transmissible neurodegenerative diseases that arise due to conformational change of normal, cellular prion protein (PrPC) to protease-resistant isofrom (rPrPSc). Deposition of misfolded PrpSc proteins leads to an alteration of many signaling pathways that includes immunological and apoptotic pathways. As a result, this culminates in the dysfunction and death of neuronal cells. Earlier works on transcriptomic studies have revealed some affected pathways, but it is not clear which is (are) the prime network pathway(s) that change during the disease progression and how these pathways are involved in crosstalks with each other from the time of incubation to clinical death. We perform network analysis on large-scale transcriptomic data of differentially expressed genes obtained from whole brain in six different mouse strain-prion strain combination models to determine the pathways involved in prion diseases, and to understand the role of crosstalks in disease propagation. We employ a notion of differential network centrality measures on protein interaction networks to identify the potential biological pathways involved. We also propose a crosstalk ranking method based on dynamic protein interaction networks to identify the core network elements involved in crosstalk with different pathways. We identify 148 DEGs (differentially expressed genes) potentially related to the prion disease progression. Functional association of the identified genes implicates a strong involvement of immunological pathways. We extract a bow-tie structure that is potentially dysregulated in prion disease. We also propose an ODE model for the bow-tie network. Predictions related to diseased condition suggests the downregulation of the core signaling elements (PI3Ks and AKTs) of the bow-tie network. In this work, we show using transcriptomic data that the neuronal dysfunction in prion disease is strongly related to the immunological pathways. We conclude that these

  2. Identification of Major Signaling Pathways in Prion Disease Progression Using Network Analysis

    PubMed Central

    Newaz, Khalique; Sriram, K.; Bera, Debajyoti

    2015-01-01

    Prion diseases are transmissible neurodegenerative diseases that arise due to conformational change of normal, cellular prion protein (PrPC) to protease-resistant isofrom (rPrPSc). Deposition of misfolded PrpSc proteins leads to an alteration of many signaling pathways that includes immunological and apoptotic pathways. As a result, this culminates in the dysfunction and death of neuronal cells. Earlier works on transcriptomic studies have revealed some affected pathways, but it is not clear which is (are) the prime network pathway(s) that change during the disease progression and how these pathways are involved in crosstalks with each other from the time of incubation to clinical death. We perform network analysis on large-scale transcriptomic data of differentially expressed genes obtained from whole brain in six different mouse strain-prion strain combination models to determine the pathways involved in prion diseases, and to understand the role of crosstalks in disease propagation. We employ a notion of differential network centrality measures on protein interaction networks to identify the potential biological pathways involved. We also propose a crosstalk ranking method based on dynamic protein interaction networks to identify the core network elements involved in crosstalk with different pathways. We identify 148 DEGs (differentially expressed genes) potentially related to the prion disease progression. Functional association of the identified genes implicates a strong involvement of immunological pathways. We extract a bow-tie structure that is potentially dysregulated in prion disease. We also propose an ODE model for the bow-tie network. Predictions related to diseased condition suggests the downregulation of the core signaling elements (PI3Ks and AKTs) of the bow-tie network. In this work, we show using transcriptomic data that the neuronal dysfunction in prion disease is strongly related to the immunological pathways. We conclude that these

  3. A geographical analysis of air pollution in the Tucson region

    NASA Astrophysics Data System (ADS)

    Diem, Jeremy Everett

    This dissertation presents a geographical analysis of air pollution in the Tucson region. Image processing, geographic information system (GIS), climatological, and statistical tools are used to develop and analyze air pollution-related databases. These databases are then used in conjunction with a limited number of spatial measurements of ozone concentrations to create accurate and theoretically sound ground-level ozone maps. High spatial resolution, gridded, multi-temporal, atmospheric emissions inventories (EIs) of ozone precursor chemical (i.e. volatile organic compounds (VOCs) and nitrogen oxides (NOx)) emissions are initially developed. GIS-driven "top-down" and "bottom-up" methods are employed to create anthropogenic VOC and NOx emissions inventories while satellite imagery and field surveys are employed to create biogenic VOC (BVOC) emissions inventories. Accounting for approximately 50% of the anthropogenic emissions, on-road vehicles are the dominant anthropogenic source. The forest and desert lands emit nearly all of the BVOCs within the entire Tucson region while exotic trees such as eucalyptus, pine, and palm emit most of the BVOCs within the City of Tucson. Relationships between VOC and NOx emissions, atmospheric conditions, and ambient ozone levels are determined by examining spatio-temporal variations in ozone levels, temporal variations in VOC and NOx emissions and atmospheric conditions, atmospheric conditions which are conducive to elevated ozone levels. In addition, the likelihood of ozone transport from Phoenix to Tucson is assessed. The highest ozone levels occur at "rural," downwind monitors, occur in August, and occur during the early afternoon hours. Atmospheric conditions conducive to elevated concentrations differ between the months while inter-city ozone transport is most likely to occur in June. Pooled, cross-sectional, times series, regression models are developed with the aid of cluster analysis and principal components analysis to

  4. Sampling and analysis of terpenes in air. An interlaboratory comparison

    NASA Astrophysics Data System (ADS)

    Larsen, Bo; Bomboi-Mingarro, Teresa; Brancaleoni, Enzo; Calogirou, Aggelos; Cecinato, Angelo; Coeur, Cecile; Chatzinestis, Ioannis; Duane, Matthew; Frattoni, Massimiliano; Fugit, Jean-Luc; Hansen, Ute; Jacob, Veronique; Mimikos, Nikolaos; Hoffmann, Thorsten; Owen, Susan; Perez-Pastor, Rosa; Reichmann, Andreas; Seufert, Gunther; Staudt, Michael; Steinbrecher, Rainer

    An interlaboratory comparison on the sampling and analysis of terpenes in air was held within the framework of the BEMA (Biogenic Emissions in the Mediterranean Area) project in May 1995. Samples were drawn and analysed by 10 European laboratories from a dynamic artificial air generator in which five terpenes were present at low ng ℓ -1 levels and ozone varied between 8 and 125 ppbv. Significant improvements over previous inter-comparison exercises in the quality of results were observed. At the ozone mixing ratio of 8 ppbv a good agreement among laboratories was obtained for all test compounds with mean values close to the target concentration. At higher mixing ratios, ozone reduced terpene recoveries and decreased the precision of the measurements due to ozonolysis during sampling. For β-pinene this effect was negligible but for the more reactive compounds significant losses were observed in some laboratories ( cis-β-ocimene = trans-β-ocimene > linalool > d-limonene). The detrimental effect of ozone was significantly lower for the laboratories which removed ozone prior to sampling by scrubbers. Parallel sampling was carried out with a standardised sampler and each individual laboratory's own device. A good agreement between the two sets of results was obtained, clearly showing that the majority of laboratories used efficient sampling systems. Two different standard solutions were analysed by each laboratory. Only in a few cases did interference in the GC separation cause problems for the quantification of the terpenes (nonanal/linalool). However, making up of standards for the calibration of the analytical equipment (GC-MS or GC-FID) was pointed out as a source of error in some laboratories.

  5. Aerosol analysis for the regional air pollution study. Final report

    SciTech Connect

    Jaklevic, J.M.; Gatti, R.C.; Goulding, F.S.; Loo, B.W.; Thompson, A.C.

    1980-05-01

    The design and operation of an aerosol sampling and analysis program implemented during the 1975 to 1977 St. Louis Regional Air Pollution Study is described. A network of ten samplers were operated at selected sites in the St. Louis area and the total mass and elemental composition of the collected particulates were determined. Sampling periods of 2 to 24 hours were employed. The samplers were capable of collecting aerosol particles in two distinct size ranges corresponding to fine (< 2.4 ..mu..m diameter) and coarse (> 2.4 ..mu..m diameter) particles. This unique feature allowed the separation of the particulate samples into two distinct fractions with differing chemical origins and health effects. The analysis methods were also newly developed for use in the St. Louis RAPS study. Total particulate mass was measured by a beta-particle attenuation method in which a precision of +- 5 ..mu..m/cm/sup 2/ could be obtained in a one minute measurement time. Elemental compositions of the samples were determined using an energy dispersive x-ray fluorescence method in which detectable limits of 5 ng/cm/sup 2/ or less were routinely achieved for elements ranging in atomic number from Al to Pb. The advantages of these analytical methods over more conventional techniques arise from the ability to automate the measurements. During the course of the two year study, a total of more than 35,000 individual samples were processed and a total of 28 concentrations measured for each sample.

  6. 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.

  7. 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

  8. 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. PMID:26270011

  9. 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

  10. Immunohistochemical Analysis of the Natural Killer Cell Cytotoxicity Pathway in Human Abdominal Aortic Aneurysms

    PubMed Central

    Hinterseher, Irene; Schworer, Charles M.; Lillvis, John H.; Stahl, Elizabeth; Erdman, Robert; Gatalica, Zoran; Tromp, Gerard; Kuivaniemi, Helena

    2015-01-01

    Our previous analysis using genome-wide microarray expression data revealed extreme overrepresentation of immune related genes belonging the Natural Killer (NK) Cell Mediated Cytotoxicity pathway (hsa04650) in human abdominal aortic aneurysm (AAA). We followed up the microarray studies by immunohistochemical analyses using antibodies against nine members of the NK pathway (VAV1, VAV3, PLCG1, PLCG2, HCST, TYROBP, PTK2B, TNFA, and GZMB) and aortic tissue samples from AAA repair operations (n = 6) and control aortae (n = 8) from age-, sex- and ethnicity-matched donors from autopsies. The results confirmed the microarray results. Two different members of the NK pathway, HCST and GRZB, which act at different steps in the NK-pathway, were actively transcribed and translated into proteins in the same cells in the AAA tissue demonstrated by double staining. Furthermore, double staining with antibodies against CD68 or CD8 together with HCST, TYROBP, PTK2B or PLCG2 revealed that CD68 and CD8 positive cells expressed proteins of the NK-pathway but were not the only inflammatory cells involved in the NK-pathway in the AAA tissue. The results provide strong evidence that the NK Cell Mediated Cytotoxicity Pathway is activated in human AAA and valuable insight for future studies to dissect the pathogenesis of human AAA. PMID:25993291

  11. Biomarker Identification and Pathway Analysis by Serum Metabolomics of Lung Cancer

    PubMed Central

    Chen, Yingrong; Ma, Zhihong; Min, Lishan; Li, Hongwei; Wang, Bin; Zhong, Jing; Dai, Licheng

    2015-01-01

    Lung cancer is one of the most common causes of cancer death, for which no validated tumor biomarker is sufficiently accurate to be useful for diagnosis. Additionally, the metabolic alterations associated with the disease are unclear. In this study, we investigated the construction, interaction, and pathways of potential lung cancer biomarkers using metabolomics pathway analysis based on the Kyoto Encyclopedia of Genes and Genomes database and the Human Metabolome Database to identify the top altered pathways for analysis and visualization. We constructed a diagnostic model using potential serum biomarkers from patients with lung cancer. We assessed their specificity and sensitivity according to the area under the curve of the receiver operator characteristic (ROC) curves, which could be used to distinguish patients with lung cancer from normal subjects. The pathway analysis indicated that sphingolipid metabolism was the top altered pathway in lung cancer. ROC curve analysis indicated that glycerophospho-N-arachidonoyl ethanolamine (GpAEA) and sphingosine were potential sensitive and specific biomarkers for lung cancer diagnosis and prognosis. Compared with the traditional lung cancer diagnostic biomarkers carcinoembryonic antigen and cytokeratin 19 fragment, GpAEA and sphingosine were as good or more appropriate for detecting lung cancer. We report our identification of potential metabolic diagnostic and prognostic biomarkers of lung cancer and clarify the metabolic alterations in lung cancer. PMID:25961003

  12. 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

  13. Identification of ambient air sampling and analysis methods for the 189 Title III air toxics

    SciTech Connect

    Mukund, R.; Kelly, T.J.; Gordon, S.M.; Hays, M.J.

    1994-12-31

    The state of development of ambient air measurement methods for the 189 Hazardous Air Pollution (HAPs) in Title 3 of the Clean Air Act Amendments was surveyed. Measurement methods for the HAPs were identified by reviews of established methods, and by literature searches for pertinent research techniques. Methods were segregated by their degree of development into Applicable, Likely, and Potential methods. This survey identified a total of 183 methods, applicable at varying degrees to ambient air measurements of one or more HAPs. As a basis for classifying the HAPs and evaluating the applicability of measurement methods, a survey of a variety of chemical and physical properties of the HAPs was also conducted. The results of both the methods and properties surveys were tabulated for each of the 189 HAP. The current state of development of ambient measurement methods for the 189 HAPs was then assessed from the results of the survey, and recommendations for method development initiatives were developed.

  14. Triple phase boundary specific pathway analysis for quantitative characterization of solid oxide cell electrode microstructure

    NASA Astrophysics Data System (ADS)

    Jørgensen, P. S.; Ebbehøj, S. L.; Hauch, A.

    2015-04-01

    The density and percolation of Triple phase boundary sites are important quantities in analyzing microstructures of solid oxide fuel cell electrodes from tomography data. However, these measures do not provide descriptions of the quality of the TPB sites in terms of the length and radius of the pathways through which they can be reached. New methods for performing TPB specific pathway analysis on 3D image data are introduced, analyzing the pathway properties of each TPB site in the electrode structure. The methods seek to provide additional information beyond whether the TPB sites are percolating or not by also analyzing the pathway length to the TPB sites and the bottleneck radius of the pathway. We show how these methods can be utilized in quantifying and relating the TPB specific results to cell test data of an electrode reduction protocol study for Ni/Scandia-and-Yttria-doped-Zirconia (Ni/ScYSZ) anodes. A study of the TPB density and particle size distribution alone did not provide an explanation for the differences observed in electrode performance. However, the analysis of pathway lengths to the TPBs and the bottleneck radii to reach these TPB sites provided valuable microstructural insight that supported the findings from the electrochemical characterization of the Ni/ScYSZ anodes.

  15. 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.

  16. 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

  17. Pathway Analysis Using Genome-Wide Association Study Data for Coronary Restenosis – A Potential Role for the PARVB Gene

    PubMed Central

    Verschuren, Jeffrey J. W.; Trompet, Stella; Sampietro, M. Lourdes; Heijmans, Bastiaan T.; Koch, Werner; Kastrati, Adnan; Houwing-Duistermaat, Jeanine J.; Slagboom, P. Eline; Quax, Paul H. A.; Jukema, J. Wouter

    2013-01-01

    Background Coronary restenosis after percutaneous coronary intervention (PCI) still remains a significant limitation of the procedure. The causative mechanisms of restenosis have not yet been fully identified. The goal of the current study was to perform gene-set analysis of biological pathways related to inflammation, proliferation, vascular function and transcriptional regulation on coronary restenosis to identify novel genes and pathways related to this condition. Methods The GENetic DEterminants of Restenosis (GENDER) databank contains genotypic data of 556,099SNPs of 295 cases with restenosis and 571 matched controls. Fifty-four pathways, related to known restenosis-related processes, were selected. Gene-set analysis was performed using PLINK, GRASS and ALIGATOR software. Pathways with a p<0.01 were fine-mapped and significantly associated SNPs were analyzed in an independent replication cohort. Results Six pathways (cell-extracellular matrix (ECM) interactions pathway, IL2 signaling pathway, IL6 signaling pathway, platelet derived growth factor pathway, vitamin D receptor pathway and the mitochondria pathway) were significantly associated in one or two of the software packages. Two SNPs in the cell-ECM interactions pathway were replicated in an independent restenosis cohort. No replication was obtained for the other pathways. Conclusion With these results we demonstrate a potential role of the cell-ECM interactions pathway in the development of coronary restenosis. These findings contribute to the increasing knowledge of the genetic etiology of restenosis formation and could serve as a hypothesis-generating effort for further functional studies. PMID:23950981

  18. 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

  19. 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

  20. 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.

  1. Pathway analysis of single-nucleotide polymorphisms potentially associated with glioblastoma multiforme susceptibility using random forests.

    PubMed

    Chang, Jeffrey S; Yeh, Ru-Fang; Wiencke, John K; Wiemels, Joseph L; Smirnov, Ivan; Pico, Alexander R; Tihan, Tarik; Patoka, Joe; Miike, Rei; Sison, Jennette D; Rice, Terri; Wrensch, Margaret R

    2008-06-01

    Glioma is a complex disease that is unlikely to result from the effect of a single gene. Genetic analysis at the pathway level involving multiple genes may be more likely to capture gene-disease associations than analyzing genes one at a time. The current pilot study included 112 Caucasians with glioblastoma multiforme and 112 Caucasian healthy controls frequency matched to cases by age and gender. Subjects were genotyped using a commercially available (ParAllele/Affymetrix) assay panel of 10,177 nonsynonymous coding single-nucleotide polymorphisms (SNP) spanning the genome known at the time the panel was constructed. For this analysis, we selected 10 pathways potentially involved in gliomagenesis that had SNPs represented on the panel. We performed random forests (RF) analyses of SNPs within each pathway group and logistic regression to assess interaction among genes in the one pathway for which the RF prediction error was better than chance and the permutation P < 0.10. Only the DNA repair pathway had a better than chance classification of case-control status with a prediction error of 45.5% and P = 0.09. Three SNPs (rs1047840 of EXO1, rs12450550 of EME1, and rs799917 of BRCA1) of the DNA repair pathway were identified as promising candidates for further replication. In addition, statistically significant interactions (P < 0.05) between rs1047840 of EXO1 and rs799917 or rs1799966 of BRCA1 were observed. Despite less than complete inclusion of genes and SNPs relevant to glioma and a small sample size, RF analysis identified one important biological pathway and several SNPs potentially associated with the development of glioblastoma. PMID:18559551

  2. ANALYSIS OF MODIFIED WET-AIR OXIDATION FOR SOIL DETOXIFICATION

    EPA Science Inventory

    The 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 conserva...

  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. Analysis of Controller Communication in En Route Air Traffic Control.

    ERIC Educational Resources Information Center

    Seamster, Thomas L.; And Others

    To contribute to an understanding of the elements of good air traffic controller communication with the objective of providing recommendations to improve controller communication training, two studies analyzed team communication, ground-air communication, and ground-line communication. The simulated and live traffic analyses examined established…

  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. An efficient hierarchical generalized linear mixed model for pathway analysis of genome-wide association studies

    PubMed Central

    Wang, Lily; Jia, Peilin; Wolfinger, Russell D.; Chen, Xi; Grayson, Britney L.; Aune, Thomas M.; Zhao, Zhongming

    2011-01-01

    Motivation: In genome-wide association studies (GWAS) of complex diseases, genetic variants having real but weak associations often fail to be detected at the stringent genome-wide significance level. Pathway analysis, which tests disease association with combined association signals from a group of variants in the same pathway, has become increasingly popular. However, because of the complexities in genetic data and the large sample sizes in typical GWAS, pathway analysis remains to be challenging. We propose a new statistical model for pathway analysis of GWAS. This model includes a fixed effects component that models mean disease association for a group of genes, and a random effects component that models how each gene's association with disease varies about the gene group mean, thus belongs to the class of mixed effects models. Results: The proposed model is computationally efficient and uses only summary statistics. In addition, it corrects for the presence of overlapping genes and linkage disequilibrium (LD). Via simulated and real GWAS data, we showed our model improved power over currently available pathway analysis methods while preserving type I error rate. Furthermore, using the WTCCC Type 1 Diabetes (T1D) dataset, we demonstrated mixed model analysis identified meaningful biological processes that agreed well with previous reports on T1D. Therefore, the proposed methodology provides an efficient statistical modeling framework for systems analysis of GWAS. Availability: The software code for mixed models analysis is freely available at http://biostat.mc.vanderbilt.edu/LilyWang. Contact: lily.wang@vanderbilt.edu; zhongming.zhao@vanderbilt.edu Supplementary information: Supplementary data are available at Bioinformatics online. PMID:21266443

  7. Reverse engineering an amyloid aggregation pathway with dimensional analysis and scaling

    NASA Astrophysics Data System (ADS)

    Bailey, J.; Potter, K. J.; Verchere, C. B.; Edelstein-Keshet, L.; Coombs, D.

    2011-12-01

    Human islet amyloid polypeptide (hIAPP) is a cytotoxic protein that aggregates into oligomers and fibrils that kill pancreatic β-cells. Here we analyze hIAPP aggregation in vitro, measured via thioflavin-T fluorescence. We use mass-action kinetics and scaling analysis to reconstruct the aggregation pathway, and find that the initiation step requires four hIAPP monomers. After this step, monomers join the nucleus in pairs, until the first stable nucleus (of size approximately 20 monomers) is formed. This nucleus then elongates by successive addition of single monomers. We find that the best-fit of our data is achieved when we include a secondary fibril-dependent nucleation pathway in the reaction scheme. We predict how interventions that change rates of fibril elongation or nucleation rates affect the accumulation of potentially cytotoxic oligomer species. Our results demonstrate the power of scaling analysis in reverse engineering biochemical aggregation pathways.

  8. Sensitivity Analysis of Intracellular Signaling Pathway Kinetics Predicts Targets for Stem Cell Fate Control

    PubMed Central

    Mahdavi, Alborz; Davey, Ryan E; Bhola, Patrick; Yin, Ting; Zandstra, Peter W

    2007-01-01

    Directing stem cell fate requires knowledge of how signaling networks integrate temporally and spatially segregated stimuli. We developed and validated a computational model of signal transducer and activator of transcription-3 (Stat3) pathway kinetics, a signaling network involved in embryonic stem cell (ESC) self-renewal. Our analysis identified novel pathway responses; for example, overexpression of the receptor glycoprotein-130 results in reduced pathway activation and increased ESC differentiation. We used a systematic in silico screen to identify novel targets and protein interactions involved in Stat3 activation. Our analysis demonstrates that signaling activation and desensitization (the inability to respond to ligand restimulation) is regulated by balancing the activation state of a distributed set of parameters including nuclear export of Stat3, nuclear phosphatase activity, inhibition by suppressor of cytokine signaling, and receptor trafficking. This knowledge was used to devise a temporally modulated ligand delivery strategy that maximizes signaling activation and leads to enhanced ESC self-renewal. PMID:17616983

  9. 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.

  10. A Pathway Analysis of Melanin Patterning in a Hemimetabolous Insect.

    PubMed

    Liu, Jin; Lemonds, Thomas R; Marden, James H; Popadić, Aleksandar

    2016-05-01

    Diversity in insect pigmentation, encompassing a wide range of colors and spatial patterns, is among the most noticeable features distinguishing species, individuals, and body regions within individuals. In holometabolous species, a significant portion of such diversity can be attributed to the melanin synthesis genes, but this has not been formally assessed in more basal insect lineages. Here we provide a comprehensive analysis of how a set of melanin genes (ebony, black, aaNAT, yellow, and tan) contributes to the pigmentation pattern in a hemipteran, Oncopeltus fasciatus For all five genes, RNA interference depletion caused alteration of black patterning in a region-specific fashion. Furthermore, the presence of distinct nonblack regions in forewings and hindwings coincides with the expression of ebony and aaNAT in these appendages. These findings suggest that the region-specific phenotypes arise from regional employment of various combinations of the melanin genes. Based on this insight, we suggest that melanin genes are used in two distinct ways: a "painting" mode, using predominantly melanin-promoting factors in areas that generally lack black coloration, and, alternatively, an "erasing" mode, using mainly melanin-suppressing factors in regions where black is the dominant pigment. Different combinations of these strategies may account for the vast diversity of melanin patterns observed in insects. PMID:26984060

  11. 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 ...

  12. Testing for mean and correlation changes in microarray experiments: an application for pathway analysis

    PubMed Central

    2010-01-01

    Background Microarray experiments examine the change in transcript levels of tens of thousands of genes simultaneously. To derive meaningful data, biologists investigate the response of genes within specific pathways. Pathways are comprised of genes that interact to carry out a particular biological function. Existing methods for analyzing pathways focus on detecting changes in the mean or over-representation of the number of differentially expressed genes relative to the total of genes within the pathway. The issue of how to incorporate the influence of correlation among the genes is not generally addressed. Results In this paper, we propose a non-parametric rank test for analyzing pathways that takes into account the correlation among the genes and compared two existing methods, Global and Gene Set Enrichment Analysis (GSEA), using two publicly available data sets. A simulation study was conducted to demonstrate the advantage of the rank test method. Conclusions The data indicate the advantages of the rank test. The method can distinguish significant changes in pathways due to either correlations or changes in the mean or both. From the simulation study the rank test out performed Global and GSEA. The greatest gain in performance was for the sample size case which makes the application of the rank test ideal for microarray experiments. PMID:20109181

  13. Biosynthetic Pathway Analysis for Improving the Cordycepin and Cordycepic Acid Production in Hirsutella sinensis.

    PubMed

    Lin, Shan; Liu, Zhi-Qiang; Xue, Ya-Ping; Baker, Peter James; Wu, Hui; Xu, Feng; Teng, Yi; Brathwaite, Mgavi Elombe; Zheng, Yu-Guo

    2016-06-01

    Hirsutella sinensis is considered as the only correct anamorph of Ophiocordyceps sinensis. To improve cordycepin and cordycepic acid production in H. sinensis, the biosynthetic pathways of cordycepin and cordycepic acid were predicted, and verified by cloning and expressing genes involved in these pathways, respectively. Then, 5'-nucleotidase participating in biosynthetic pathway of cordycepin, hexokinase, and glucose phosphate isomerase involved in biosynthetic pathway of cordycepic acid, were demonstrated playing important roles in the corresponding biosynthetic pathway by real-time PCR, accompanying with significantly up-regulated 15.03-, 5.27-, and 3.94-fold, respectively. Moreover, the metabolic regulation of H. sinensis was performed. As expected, cordycepin production reached 1.09 mg/g when additional substrate of 5'-nucleotidase was 4 mg/mL, resulting in an increase of 201.1 % compared with the control. In the same way, cordycepic acid production reached 26.6 and 23.4 % by adding substrate of hexokinase or glucose phosphate isomerase, leading to a rise of 77.3 and 55.1 %, respectively. To date, this is the first time to improve cordycepin and cordycepic acid production through metabolic regulation based on biosynthetic pathway analysis, and metabolic regulation is proved as a simple and effective way to enhance the output of cordycepin and cordycepic acid in submerged cultivation of H. sinensis. PMID:26922724

  14. 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.

  15. Photochemistry of the Martian atmosphere: Pathway analysis of ozone formation and destruction

    NASA Astrophysics Data System (ADS)

    Stock, J. W.; Boxe, C. S.; Lehmann, R.; Grenfell, J. L.; Patzer, A. B. C.; Rauer, H.; Yung, Y. L.

    2012-04-01

    Ozone is of central importance for the Martian atmosphere, because e.g. it is related to the photochemical stability of the main atmospheric constituent, CO2. Furthermore, ozone is relatively easy to observe, since it exhibits strong spectral features. The concentration of ozone is influenced by chemical trace species (mainly from the Ox- and HOx-family) acting as catalysts in chemical pathways. It is therefore desirable to identify those pathways and quantify their efficiency by calculating pathway rates. Finding chemical pathways in complex reaction networks is in general challenging. Therefore, automated computer algorithms are useful to address such problems. In order to investigate the Martian atmospheric ozone photochemistry, we apply the PAP (Pathway Analysis Program) algorithm to the results of the updated JPL/Caltech photochemical column model of the Martian atmosphere. Rates of individual ozone production and destruction pathways are computed for different altitudes, by applying the algorithm to each vertical layer of the column model separately. Our findings show, that ozone is primarily produced by a Chapman-like mechanism involving CO2 photolysis products as source for atomic oxygen. Ozone destruction proceeds mainly via photolysis except for a layer around 42km where the reaction with atomic hydrogen become more important.

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

    PubMed

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

    2016-01-20

    The hydrogen production electrocatalyst Ni(P(Ph)2N(Ph)2)2(2+) (1) is capable of traversing multiple electrocatalytic pathways. When using dimethylformamidium, DMF(H)(+), the mechanism of H2 formation by 1 changes from an ECEC to an EECC mechanism as the potential approaches the Ni(I/0) couple. Two electrochemical methods, current-potential analysis and foot-of-the-wave analysis (FOWA), were performed on 1 to measure detailed kinetics of the competing ECEC and EECC pathways. A sensitivity analysis was performed on the methods using digital simulations to understand their strengths and limitations. Chemical rate constants were significantly underestimated when not accounting for electron-transfer kinetics, even when electron transfer was fast enough to afford a reversible noncatalytic wave. The EECC pathway of 1 was faster than the ECEC pathway under all conditions studied. Buffered DMF:DMF(H)(+) mixtures afforded an increase in the catalytic rate constant (k(obs)) of the EECC pathway, but k(obs) for the ECEC pathway did not change when using buffered acid. Further kinetic analysis of the ECEC path revealed that base increases the rate of isomerization from exo-protonated Ni(0) isomers to the catalytically active endo-isomers, but decreases the rate of protonation of Ni(I). FOWA did not provide accurate rate constants, but FOWA was used to estimate the reduction potential of the previously undetected exo-protonated Ni(I) intermediate. Comparison of catalytic Tafel plots for 1 under different conditions reveals substantial inaccuracies in the turnover frequency at zero overpotential when the kinetic and thermodynamic effects of the conjugate base are not accounted for properly. PMID:26692398

  17. 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.

  18. Bioinformatics analysis of differentially expressed pathways related to the metastatic characteristics of osteosarcoma

    PubMed Central

    Sun, Wei; Ma, Xiaojun; Shen, Jiakang; Yin, Fei; Wang, Chongren; Cai, Zhengdong

    2016-01-01

    In this study, gene expression data of osteosarcoma (OSA) were analyzed to identify metastasis-related biological pathways. Four gene expression data sets (GSE21257, GSE9508, GSE49003 and GSE66673) were downloaded from Gene Expression Omnibus (GEO). An analysis of differentially expressed genes (DEGs) was performed using the Significance Analysis of Microarray (SAM) method. Gene expression levels were converted into scores of pathways by the Functional Analysis of Individual Microarray Expression (FAIME) algorithm and the differentially expressed pathways (DEPs) were then disclosed by a t-test. The distinguishing and prediction ability of the DEPs for metastatic and non-metastatic OSA was further confirmed using the principal component analysis (PCA) method and 3 gene expression data sets (GSE9508, GSE49003 and GSE66673) based on the support vector machines (SVM) model. A total of 616 downregulated and 681 upregulated genes were identified in the data set, GSE21257. The DEGs could not be used to distinguish metastatic OSA from non-metastatic OSA, as shown by PCA. Thus, an analysis of DEPs was further performed, resulting in 14 DEPs, such as NRAS signaling, Toll-like receptor (TLR) signaling, matrix metalloproteinase (MMP) regulation of cytokines and tumor necrosis factor receptor-associated factor (TRAF)-mediated interferon regulatory factor 7 (IRF7) activation. Cluster analysis indicated that these pathways could be used to distinguish between metastatic OSA from non-metastatic OSA. The prediction accuracy was 91, 66.7 and 87.5% for the data sets, GSE9508, GSE49003 and GSE66673, respectively. The results of PCA further validated that the DEPs could be used to distinguish metastatic OSA from non-metastatic OSA. On the whole, several DEPs were identified in metastatic OSA compared with non-metastatic OSA. Further studies on these pathways and relevant genes may help to enhance our understanding of the molecular mechanisms underlying metastasis and may thus aid in

  19. Meta-Analysis of Placental Transcriptome Data Identifies a Novel Molecular Pathway Related to Preeclampsia.

    PubMed

    van Uitert, Miranda; Moerland, Perry D; Enquobahrie, Daniel A; Laivuori, Hannele; van der Post, Joris A M; Ris-Stalpers, Carrie; Afink, Gijs B

    2015-01-01

    Studies using the placental transcriptome to identify key molecules relevant for preeclampsia are hampered by a relatively small sample size. In addition, they use a variety of bioinformatics and statistical methods, making comparison of findings challenging. To generate a more robust preeclampsia gene expression signature, we performed a meta-analysis on the original data of 11 placenta RNA microarray experiments, representing 139 normotensive and 116 preeclamptic pregnancies. Microarray data were pre-processed and analyzed using standardized bioinformatics and statistical procedures and the effect sizes were combined using an inverse-variance random-effects model. Interactions between genes in the resulting gene expression signature were identified by pathway analysis (Ingenuity Pathway Analysis, Gene Set Enrichment Analysis, Graphite) and protein-protein associations (STRING). This approach has resulted in a comprehensive list of differentially expressed genes that led to a 388-gene meta-signature of preeclamptic placenta. Pathway analysis highlights the involvement of the previously identified hypoxia/HIF1A pathway in the establishment of the preeclamptic gene expression profile, while analysis of protein interaction networks indicates CREBBP/EP300 as a novel element central to the preeclamptic placental transcriptome. In addition, there is an apparent high incidence of preeclampsia in women carrying a child with a mutation in CREBBP/EP300 (Rubinstein-Taybi Syndrome). The 388-gene preeclampsia meta-signature offers a vital starting point for further studies into the relevance of these genes (in particular CREBBP/EP300) and their concomitant pathways as biomarkers or functional molecules in preeclampsia. This will result in a better understanding of the molecular basis of this disease and opens up the opportunity to develop rational therapies targeting the placental dysfunction causal to preeclampsia. PMID:26171964

  20. Meta-Analysis of Placental Transcriptome Data Identifies a Novel Molecular Pathway Related to Preeclampsia

    PubMed Central

    van Uitert, Miranda; Moerland, Perry D.; Enquobahrie, Daniel A.; Laivuori, Hannele; van der Post, Joris A. M.; Ris-Stalpers, Carrie; Afink, Gijs B.

    2015-01-01

    Studies using the placental transcriptome to identify key molecules relevant for preeclampsia are hampered by a relatively small sample size. In addition, they use a variety of bioinformatics and statistical methods, making comparison of findings challenging. To generate a more robust preeclampsia gene expression signature, we performed a meta-analysis on the original data of 11 placenta RNA microarray experiments, representing 139 normotensive and 116 preeclamptic pregnancies. Microarray data were pre-processed and analyzed using standardized bioinformatics and statistical procedures and the effect sizes were combined using an inverse-variance random-effects model. Interactions between genes in the resulting gene expression signature were identified by pathway analysis (Ingenuity Pathway Analysis, Gene Set Enrichment Analysis, Graphite) and protein-protein associations (STRING). This approach has resulted in a comprehensive list of differentially expressed genes that led to a 388-gene meta-signature of preeclamptic placenta. Pathway analysis highlights the involvement of the previously identified hypoxia/HIF1A pathway in the establishment of the preeclamptic gene expression profile, while analysis of protein interaction networks indicates CREBBP/EP300 as a novel element central to the preeclamptic placental transcriptome. In addition, there is an apparent high incidence of preeclampsia in women carrying a child with a mutation in CREBBP/EP300 (Rubinstein-Taybi Syndrome). The 388-gene preeclampsia meta-signature offers a vital starting point for further studies into the relevance of these genes (in particular CREBBP/EP300) and their concomitant pathways as biomarkers or functional molecules in preeclampsia. This will result in a better understanding of the molecular basis of this disease and opens up the opportunity to develop rational therapies targeting the placental dysfunction causal to preeclampsia. PMID:26171964

  1. [De novotranscriptomic analysis of Chlorella sorokiniana: Pathway description and gene discovery for lipid production ].

    PubMed

    Li, Lin; Wang, Qinhong; Yang, Hailin; Wang, Wu

    2014-09-01

    [ OBJECTIVE] The paucity of genomic information limits the metabolic engineering of non-model microalgae Chlorella sorokiniana. Our study aimed to elucidate the fatty acid, triacylglycerol and starch biosynthetic pathways in the microalgae C. sorokiniana based on de novo transcriptomic analysis. [METHODS] We cultured C. sorokiniana with different nitrogen concentrations (KNO3: 8g/L and 2g/L) , then sequenced the transcriptomeusing Illumina Hiseq2000 platform. We used Trinity to de novo assemble the reads so as to obtain transcripts, aligned all the transcripts with Nr database, UniProtKB/Swiss-Prot database and COG database to annotate the function and classify using BLASTx algorithm, and assigned the transcript with metabolic pathway by aligning with KEGG database. Then we used RSEM to calculate FPKM value, and used it for preliminary analysis of different gene expression in the related pathways. [RESULTS] Over 49M high quality raw reads were produced with the length of 100bp, We used Trinity to assembled these reads into 49885 transcripts with an N50 of 1941bp, ranging from 300bp to 14100bp. 26479 transcripts were annotated through BLASTx similarity search, 2357 transcripts were assigned with EC number, and 207 metabolic pathways were assigned in total. Based on these analyses, we reconstructed the fatty acids, triacylglycerol and starch biosynthetic pathways in C. sorokiniana. We also identified preliminarily different geneexpression in the pathways. [CONCLUSION] Using RNA-seq technology, we reconstructed the metabolic pathways involving in the fatty acid, triacylglycerol and starch biosynthesis in non-model microalgae C. sorokiniana without genomic data, which is consistent with those in model microalgae Chlamydomonas reinhardtii, and compared the gene expression level under different conditions. These information is very useful for the metabolic engineering of C. sorokiniana and other microalgae to enhance the production of lipids. PMID:25522590

  2. Comprehensive Detection of Genes Causing a Phenotype Using Phenotype Sequencing and Pathway Analysis

    PubMed Central

    Harper, Marc; Gronenberg, Luisa; Liao, James; Lee, Christopher

    2014-01-01

    Discovering all the genetic causes of a phenotype is an important goal in functional genomics. We combine an experimental design for detecting independent genetic causes of a phenotype with a high-throughput sequencing analysis that maximizes sensitivity for comprehensively identifying them. Testing this approach on a set of 24 mutant strains generated for a metabolic phenotype with many known genetic causes, we show that this pathway-based phenotype sequencing analysis greatly improves sensitivity of detection compared with previous methods, and reveals a wide range of pathways that can cause this phenotype. We demonstrate our approach on a metabolic re-engineering phenotype, the PEP/OAA metabolic node in E. coli, which is crucial to a substantial number of metabolic pathways and under renewed interest for biofuel research. Out of 2157 mutations in these strains, pathway-phenoseq discriminated just five gene groups (12 genes) as statistically significant causes of the phenotype. Experimentally, these five gene groups, and the next two high-scoring pathway-phenoseq groups, either have a clear connection to the PEP metabolite level or offer an alternative path of producing oxaloacetate (OAA), and thus clearly explain the phenotype. These high-scoring gene groups also show strong evidence of positive selection pressure, compared with strictly neutral selection in the rest of the genome. PMID:24586303

  3. Probabilistic approach to identify sensitive parameter distributions in multimedia pathway analysis.

    SciTech Connect

    Kamboj, S.; Gnanapragasam, E.; LePoire, D.; Biwer, B. M.; Cheng, J.; Arnish, J.; Yu, C.; Chen, S. Y.; Mo, T.; Abu-Eid, R.; Thaggard, M.; Environmental Assessment; NRC

    2002-01-01

    Sensitive parameter distributions were identified with the use of probabilistic analysis in the RESRAD computer code. RESRAD is a multimedia pathway analysis code designed to evaluate radiological exposures resulting from radiological contamination in soil. The dose distribution was obtained by using a set of default parameter distribution/values. Most of the variations in the output dose distribution could be attributed to uncertainty in a small set of input parameters that could be considered as sensitive parameter distributions. The identification of the sensitive parameters is a first step in the prioritization of future research and information gathering. When site-specific parameter distribution/values are available for an actual site, the same process should be used with these site-specific data. Regression analysis used to identify sensitive parameters indicated that the dominant pathways depended on the radionuclide and source configurations. However, two parameter distributions were sensitive for many radionuclides: the external shielding factor when external exposure was the dominant pathway and the plant transfer factor when plant ingestion was the dominant pathway. No single correlation or regression coefficient can be used alone to identify sensitive parameters in all the cases. The coefficients are useful guides, but they have to be used in conjunction with other aids, such as scatter plots, and should undergo further analysis.

  4. 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...

  5. SNP-based pathway enrichment analysis for genome-wide association studies

    PubMed Central

    2011-01-01

    Background Recently we have witnessed a surge of interest in using genome-wide association studies (GWAS) to discover the genetic basis of complex diseases. Many genetic variations, mostly in the form of single nucleotide polymorphisms (SNPs), have been identified in a wide spectrum of diseases, including diabetes, cancer, and psychiatric diseases. A common theme arising from these studies is that the genetic variations discovered by GWAS can only explain a small fraction of the genetic risks associated with the complex diseases. New strategies and statistical approaches are needed to address this lack of explanation. One such approach is the pathway analysis, which considers the genetic variations underlying a biological pathway, rather than separately as in the traditional GWAS studies. A critical challenge in the pathway analysis is how to combine evidences of association over multiple SNPs within a gene and multiple genes within a pathway. Most current methods choose the most significant SNP from each gene as a representative, ignoring the joint action of multiple SNPs within a gene. This approach leads to preferential identification of genes with a greater number of SNPs. Results We describe a SNP-based pathway enrichment method for GWAS studies. The method consists of the following two main steps: 1) for a given pathway, using an adaptive truncated product statistic to identify all representative (potentially more than one) SNPs of each gene, calculating the average number of representative SNPs for the genes, then re-selecting the representative SNPs of genes in the pathway based on this number; and 2) ranking all selected SNPs by the significance of their statistical association with a trait of interest, and testing if the set of SNPs from a particular pathway is significantly enriched with high ranks using a weighted Kolmogorov-Smirnov test. We applied our method to two large genetically distinct GWAS data sets of schizophrenia, one from European

  6. Comprehensive analysis of migration pathways (CAMP): Contaminant migration pathways at confined dredged material-disposal facilities. Final report

    SciTech Connect

    Brannon, J.M.; Pennington, J.C.; Gunnison, D.; Myers, T.E.

    1990-09-01

    A confined disposal facility (CDF) is a diked enclosure having either permeable or low-permeable walls that are used to retain dredged material solids. There are two types of CDFs are located within the influence of normal tidal or other water fluctuations. This report identifies and documents key contaminant mobility processes and pathways operative in CDFs under varying operational and environmental conditions. It also summarizes what is known about contaminant migration, cycling, and mobilization pathways, provides information on models and assessment techniques, and identifies areas for which insufficient information is available. The present information does not permit evaluations of the relative significance of contaminant migration pathways from a CDF. Pathways involving movement of large masses of water, such as CDF effluent, leaching through permeable dikes, or leaching through the dredged material, have the greatest potential for moving significant quantities of contaminants out of the CDF. Pathways such as volatilization may also result in movement of substantial amounts of volatile organic contaminants from CDFs. The relative importance of contaminant cycling and mobilization pathways to net mass balance has not been determined, but available information on each of the contaminant migration, cycling, and mobilization pathways is summarized in the report. Where possible, methods have been provided for making rough estimates of contaminant mass movement via pathways.

  7. Axonal guidance signaling pathway interacting with smoking in modifying the risk of pancreatic cancer: a gene- and pathway-based interaction analysis of GWAS data

    PubMed Central

    Li, Donghui

    2014-01-01

    Cigarette smoking is the best established modifiable risk factor for pancreatic cancer. Genetic factors that underlie smoking-related pancreatic cancer have previously not been examined at the genome-wide level. Taking advantage of the existing Genome-wide association study (GWAS) genotype and risk factor data from the Pancreatic Cancer Case Control Consortium, we conducted a discovery study in 2028 cases and 2109 controls to examine gene–smoking interactions at pathway/gene/single nucleotide polymorphism (SNP) level. Using the likelihood ratio test nested in logistic regression models and ingenuity pathway analysis (IPA), we examined 172 KEGG (Kyoto Encyclopedia of Genes and Genomes) pathways, 3 manually curated gene sets, 3 nicotine dependency gene ontology pathways, 17 912 genes and 468 114 SNPs. None of the individual pathway/gene/SNP showed significant interaction with smoking after adjusting for multiple comparisons. Six KEGG pathways showed nominal interactions (P < 0.05) with smoking, and the top two are the pancreatic secretion and salivary secretion pathways (major contributing genes: RAB8A, PLCB and CTRB1). Nine genes, i.e. ZBED2, EXO1, PSG2, SLC36A1, CLSTN1, MTHFSD, FAT2, IL10RB and ATXN2 had P interaction < 0.0005. Five intergenic region SNPs and two SNPs of the EVC and KCNIP4 genes had P interaction < 0.00003. In IPA analysis of genes with nominal interactions with smoking, axonal guidance signaling (P=2.12×10−7) and α-adrenergic signaling (P=2.52×10−5) genes were significantly overrepresented canonical pathways. Genes contributing to the axon guidance signaling pathway included the SLIT/ROBO signaling genes that were frequently altered in pancreatic cancer. These observations need to be confirmed in additional data set. Once confirmed, it will open a new avenue to unveiling the etiology of smoking-associated pancreatic cancer. PMID:24419231

  8. Wave intensity analysis in air-filled flexible vessels.

    PubMed

    Clavica, Francesco; Parker, Kim H; Khir, Ashraf W

    2015-02-26

    Wave intensity analysis (WIA) is an analytical technique generally used to investigate the propagation of waves in the cardiovascular system. Despite its increasing usage in the cardiovascular system, to our knowledge WIA has never been applied to the respiratory system. Given the analogies between arteries and airways (i.e. fluid flow in flexible vessels), the aim of this work is to test the applicability of WIA with gas flow instead of liquid flow. The models employed in this study are similar to earlier studies used for arterial investigations. Simultaneous pressure (P) and velocity (U) measurements were initially made in a single tube and then in several flexible tubes connected in series. Wave speed was calculated using the foot-to-foot method (cf), which was used to separate analytically the measured P and U waveforms into their forward and backward components. Further, the data were used to calculate wave intensity, which was also separated into its forward and backward components. Although the measured wave speed was relatively high, the results showed that the onsets and the nature of reflections (compression/expansion) derived with WIA, corresponded well to those anticipated using the theory of waves in liquid-filled elastic tubes. On average the difference between the experimental and theoretical arrival time of reflection was 6.1% and 3.6% for the single vessel and multivessel experiment, respectively. The results suggest that WIA can provide relatively accurate information on reflections in air-filled flexible tubes, warranting further studies to explore the full potential of this technique in the respiratory system. PMID:25595424

  9. Association genetics and transcriptome analysis reveal a gibberellin-responsive pathway involved in regulating photosynthesis.

    PubMed

    Xie, Jianbo; Tian, Jiaxing; Du, Qingzhang; Chen, Jinhui; Li, Ying; Yang, Xiaohui; Li, Bailian; Zhang, Deqiang

    2016-05-01

    Gibberellins (GAs) regulate a wide range of important processes in plant growth and development, including photosynthesis. However, the mechanism by which GAs regulate photosynthesis remains to be understood. Here, we used multi-gene association to investigate the effect of genes in the GA-responsive pathway, as constructed by RNA sequencing, on photosynthesis, growth, and wood property traits, in a population of 435 Populus tomentosa By analyzing changes in the transcriptome following GA treatment, we identified many key photosynthetic genes, in agreement with the observed increase in measurements of photosynthesis. Regulatory motif enrichment analysis revealed that 37 differentially expressed genes related to photosynthesis shared two essential GA-related cis-regulatory elements, the GA response element and the pyrimidine box. Thus, we constructed a GA-responsive pathway consisting of 47 genes involved in regulating photosynthesis, including GID1, RGA, GID2, MYBGa, and 37 photosynthetic differentially expressed genes. Single nucleotide polymorphism (SNP)-based association analysis showed that 142 SNPs, representing 40 candidate genes in this pathway, were significantly associated with photosynthesis, growth, and wood property traits. Epistasis analysis uncovered interactions between 310 SNP-SNP pairs from 37 genes in this pathway, revealing possible genetic interactions. Moreover, a structural gene-gene matrix based on a time-course of transcript abundances provided a better understanding of the multi-gene pathway affecting photosynthesis. The results imply a functional role for these genes in mediating photosynthesis, growth, and wood properties, demonstrating the potential of combining transcriptome-based regulatory pathway construction and genetic association approaches to detect the complex genetic networks underlying quantitative traits. PMID:27091876

  10. 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...

  11. Car indoor air pollution - analysis of potential sources

    PubMed Central

    2011-01-01

    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. PMID:22177291

  12. 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...

  13. INCORPORATING UNCERTAINTY ANALYSIS INTO INTEGRATED AIR QUALITY PLANNING

    EPA Science Inventory

    The proposed research will develop methods by which air quality planners could formally consider the uncertainty of models that inform control strategy development. We will identify key photochemical model inputs, epidemiological parameters, and other assumptions that most in...

  14. The Argonne radon-in-air analysis system

    SciTech Connect

    Lucas, H.F.

    1995-12-31

    The methods used or developed at Argonne National Laboratory (ANL) for the measurement of radon in air are being summarized here. The radon calibration work has been entirely maintained during the last several years by F. Markun (Analytic Services Section).

  15. A comparative analysis of the DNA recombination repair pathway in mycobacterial genomes.

    PubMed

    Singh, Amandeep; Bhagavat, Raghu; Vijayan, M; Chandra, Nagasuma

    2016-07-01

    In prokaryotes, repair by homologous recombination provides a major means to reinstate the genetic information lost in DNA damage. Recombination repair pathway in mycobacteria has multiple differences as compared to that in Escherichia coli. Of about 20 proteins known to be involved in the pathway, a set of 9 proteins, namely, RecF, RecO, RecR, RecA, SSBa, RuvA, RuvB and RuvC was found to be indispensable among the 43 mycobacterial strains. A domain level analysis indicated that most domains involved in recombination repair are unique to these proteins and are present as single copies in the genomes. Synteny analysis reveals that the gene order of proteins involved in the pathway is not conserved, suggesting that they may be regulated differently in different species. Sequence conservation among the same protein from different strains suggests the importance of RecO-RecA and RecFOR-RecA presynaptic pathways in the repair of double strand-breaks and single strand-breaks respectively. New annotations obtained from the analysis, include identification of a protein with a probable Holliday junction binding role present in 41 mycobacterial genomes and that of a RecB-like nuclease, containing a cas4 domain, present in 42 genomes. New insights into the binding of small molecules to the relevant proteins are provided by binding pocket analysis using three dimensional structural models. Analysis of the various features of the recombination repair pathway, presented here, is likely to provide a framework for further exploring stress response and emergence of drug resistance in mycobacteria. PMID:27450012

  16. 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.

  17. 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.

  18. Provenance and Pathways: A Geochemical and Isotopic Analysis of Mt. Shasta Groundwater

    NASA Astrophysics Data System (ADS)

    McClain, C. N.; Mount, J. F.; Zierenberg, R. A.; Fogg, G. E.; Dahlgren, R. A.

    2008-12-01

    Geochemical, isotopic and temperature data from springs at Mt. Shasta are analyzed to characterize origins and pathways of the groundwater. Three main types of springs exist at Mt. Shasta, California, based on temperature and chemical composition: (1) non-thermal, with temperature the same or lower than mean annual air temperature (2) slightly-thermal, with temperature above mean annual air temperature, but less than 10 degrees Celsius above, usually containing elevated levels of dissolved constituents found in thermal waters (3) mineral, with TDS >400mg/L. The presence of elevated levels of boron, nitrogen, phosphorous and carbon in any of these spring waters at Mt. Shasta suggests that there has been interaction with metasedimentary rocks thought to underlie the Cascade stratovolcano. Elevated temperatures in slightly- thermal springs can be explained by deep circulation pathways or by interaction with shallower hydrothermal fluids that originate from volcanic processes. The source of the chemical composition and temperature of the slightly-thermal springs is important because these springs contribute a large portion of the baseflow of the Shasta River, an important ecosystem for anadromous fish. Stable carbon isotopic composition (δ13C) and radiocarbon measurements of mineral springs suggest that there is a mixed source of carbon including a magmatic component and an old organic component, such as what could be found in local metasedimentary rocks. Due to the chemical composition, temperature and location of these mineral springs it is unlikely that they are associated with the hydrothermal system at Mt. Shasta.

  19. Crosstalk analysis of pathways in breast cancer using a network model based on overlapping differentially expressed genes

    PubMed Central

    SUN, YONG; YUAN, KAI; ZHANG, PENG; MA, RONG; ZHANG, QI-WEN; TIAN, XING-SONG

    2015-01-01

    Multiple signal transduction pathways can affect each other considerably through crosstalk. However, the presence and extent of this phenomenon have not been rigorously studied. The aim of the present study was to identify strong and normal interactions between pathways in breast cancer and determine the main pathway. Five sets of breast cancer data were downloaded from the high-throughput Gene Expression Omnibus (GEO) and analyzed to identify differentially expressed (DE) genes using the Rank Product (RankProd) method. A list of pathways with differential expression was obtained by gene set enrichment analysis (GSEA) of the Kyoto Encyclopedia of Genes and Genomes (KEGG) database. The DE genes that overlapped between pathways were identified and a crosstalk network diagram based on the overlap of DE genes was constructed. A total of 1,464 DE genes and 26 pathways were identified. In addition, the number of DE genes that overlapped between specific pathways were determined, and the greatest degree of overlap was between the extracellular matrix (ECM)-receptor interaction and Focal adhesion pathways, which had 22 overlapping DE genes. Weighted pathway analysis of the crosstalk between pathways identified that Pathways in cancer was the main pathway in breast cancer. PMID:26622386

  20. 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. PMID:26871867

  1. New insights in Rett syndrome using pathway analysis for transcriptomics data.

    PubMed

    Ehrhart, Friederike; Coort, Susan L M; Cirillo, Elisa; Smeets, Eric; Evelo, Chris T; Curfs, Leopold

    2016-09-01

    The analysis of transcriptomics data is able to give an overview of cellular processes, but requires sophisticated bioinformatics tools and methods to identify the changes. Pathway analysis software, like PathVisio, captures the information about biological pathways from databases and brings this together with the experimental data to enable visualization and understanding of the underlying processes. Rett syndrome is a rare disease, but still one of the most abundant causes of intellectual disability in females. Cause of this neurological disorder is mutation of one single gene, the methyl-CpG-binding protein 2 (MECP2) gene. This gene is responsible for many steps in neuronal development and function. Although the genetic mutation and the clinical phenotype are well described, the molecular pathways linking them are not yet fully elucidated. In this study we demonstrate a workflow for the analysis of transcriptomics data to identify biological pathways and processes which are changed in a Mecp2 (-/y) mouse model. PMID:27517371

  2. 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.

  3. 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

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

    PubMed

    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

  5. Genome-Wide Transcriptome Directed Pathway Analysis of Maternal Pre-Eclampsia Susceptibility Genes

    PubMed Central

    Yong, Hannah E. J.; Melton, Phillip E.; Johnson, Matthew P.; Freed, Katy A.; Kalionis, Bill; Murthi, Padma; Brennecke, Shaun P.; Keogh, Rosemary J.; Moses, Eric K.

    2015-01-01

    Background Preeclampsia (PE) is a serious hypertensive pregnancy disorder with a significant genetic component. Numerous genetic studies, including our own, have yielded many susceptibility genes from distinct functional groups. Additionally, transcriptome profiling of tissues at the maternal-fetal interface has likewise yielded many differentially expressed genes. Often there is little overlap between these two approaches, although genes identified in both approaches are significantly associated with PE. We have thus taken a novel integrative bioinformatics approach of analysing pathways common to the susceptibility genes and the PE transcriptome. Methods Using Illumina Human Ht12v4 and Wg6v3 BeadChips, transcriptome profiling was conducted on n = 65 normotensive and n = 60 PE decidua basalis tissues collected at delivery. The R software package libraries lumi and limma were used to preprocess transcript data for pathway analysis. Pathways were analysed and constructed using Pathway Studio. We examined ten candidate genes, which are from these functional groups: activin/inhibin signalling—ACVR1, ACVR1C, ACVR2A, INHA, INHBB; structural components—COL4A1, COL4A2 and M1 family aminopeptidases—ERAP1, ERAP2 and LNPEP. Results/Conclusion Major common regulators/targets of these susceptibility genes identified were AGT, IFNG, IL6, INHBA, SERPINE1, TGFB1 and VEGFA. The top two categories of pathways associated with the susceptibility genes, which were significantly altered in the PE decidual transcriptome, were apoptosis and cell signaling (p < 0.001). Thus, susceptibility genes from distinct functional groups share similar downstream pathways through common regulators/targets, some of which are altered in PE. This study contributes to a better understanding of how susceptibility genes may interact in the development of PE. With this knowledge, more targeted functional analyses of PE susceptibility genes in these key pathways can be performed to examine their

  6. Biosynthetic Pathway for the Epipolythiodioxopiperazine Acetylaranotin in Aspergillus terreus Revealed by Genome-based Deletion Analysis

    SciTech Connect

    Guo, Chun-Jun; Yeh, Hsu-Hua; Chiang, Yi Ming; Sanchez, James F.; Chang, ShuLin; Bruno, Kenneth S.; Wang, Clay C.

    2013-04-15

    Abstract Epipolythiodioxopiperazines (ETPs) are a class of fungal secondary metabolites derived from cyclic peptides. Acetylaranotin belongs to one structural subgroup of ETPs characterized by the presence of a seven-membered dihydrooxepine ring. Defining the genes involved in acetylaranotin biosynthesis should provide a means to increase production of these compounds and facilitate the engineering of second-generation molecules. The filamentous fungus Aspergillus terreus produces acetylaranotin and related natural products. Using targeted gene deletions, we have identified a cluster of 9 genes including one nonribosomal peptide synthase gene, ataP, that is required for acetylaranotin biosynthesis. Chemical analysis of the wild type and mutant strains enabled us to isolate seventeen natural products that are either intermediates in the normal biosynthetic pathway or shunt products that are produced when the pathway is interrupted through mutation. Nine of the compounds identified in this study are novel natural products. Our data allow us to propose a complete biosynthetic pathway for acetylaranotin and related natural products.

  7. A general definition of metabolic pathways useful for systematic organization and analysis of complex metabolic networks.

    PubMed

    Schuster, S; Fell, D A; Dandekar, T

    2000-03-01

    A set of linear pathways often does not capture the full range of behaviors of a metabolic network. The concept of 'elementary flux modes' provides a mathematical tool to define and comprehensively describe all metabolic routes that are both stoichiometrically and thermodynamically feasible for a group of enzymes. We have used this concept to analyze the interplay between the pentose phosphate pathway (PPP) and glycolysis. The set of elementary modes for this system involves conventional glycolysis, a futile cycle, all the modes of PPP function described in biochemistry textbooks, and additional modes that are a priori equally entitled to pathway status. Applications include maximizing product yield in amino acid and antibiotic synthesis, reconstruction and consistency checks of metabolism from genome data, analysis of enzyme deficiencies, and drug target identification in metabolic networks. PMID:10700151

  8. Analysis of PIK3CA Mutations and Activation Pathways in Triple Negative Breast Cancer

    PubMed Central

    Muroni, Maria Rosaria; Sanges, Francesca; Sotgiu, Giovanni; Ena, Sara; Pira, Giovanna; Murgia, Luciano; Manca, Alessandra; Uras, Maria Gabriela; Sarobba, Maria Giuseppina; Urru, Silvana; De Miglio, Maria Rosaria

    2015-01-01

    Background Triple Negative Breast Cancer (TNBC) accounts for 12–24% of all breast carcinomas, and shows worse prognosis compared to other breast cancer subtypes. Molecular studies demonstrated that TNBCs are a heterogeneous group of tumors with different clinical and pathologic features, prognosis, genetic-molecular alterations and treatment responsivity. The PI3K/AKT is a major pathway involved in the regulation of cell survival and proliferation, and is the most frequently altered pathway in breast cancer, apparently with different biologic impact on specific cancer subtypes. The most common genetic abnormality is represented by PIK3CA gene activating mutations, with an overall frequency of 20–40%. The aims of our study were to investigate PIK3CA gene mutations on a large series of TNBC, to perform a wider analysis on genetic alterations involving PI3K/AKT and BRAF/RAS/MAPK pathways and to correlate the results with clinical-pathologic data. Materials and Methods PIK3CA mutation analysis was performed by using cobas® PIK3CA Mutation Test. EGFR, AKT1, BRAF, and KRAS genes were analyzed by sequencing. Immunohistochemistry was carried out to identify PTEN loss and to investigate for PI3K/AKT pathways components. Results PIK3CA mutations were detected in 23.7% of TNBC, whereas no mutations were identified in EGFR, AKT1, BRAF, and KRAS genes. Moreover, we observed PTEN loss in 11.3% of tumors. Deregulation of PI3K/AKT pathways was revealed by consistent activation of pAKT and p-p44/42 MAPK in all PIK3CA mutated TNBC. Conclusions Our data shows that PIK3CA mutations and PI3K/AKT pathway activation are common events in TNBC. A deeper investigation on specific TNBC genomic abnormalities might be helpful in order to select patients who would benefit from current targeted therapy strategies. PMID:26540293

  9. Gene interaction enrichment and network analysis to identify dysregulated pathways and their interactions in complex diseases

    PubMed Central

    2012-01-01

    Background The molecular behavior of biological systems can be described in terms of three fundamental components: (i) the physical entities, (ii) the interactions among these entities, and (iii) the dynamics of these entities and interactions. The mechanisms that drive complex disease can be productively viewed in the context of the perturbations of these components. One challenge in this regard is to identify the pathways altered in specific diseases. To address this challenge, Gene Set Enrichment Analysis (GSEA) and others have been developed, which focus on alterations of individual properties of the entities (such as gene expression). However, the dynamics of the interactions with respect to disease have been less well studied (i.e., properties of components ii and iii). Results Here, we present a novel method called Gene Interaction Enrichment and Network Analysis (GIENA) to identify dysregulated gene interactions, i.e., pairs of genes whose relationships differ between disease and control. Four functions are defined to model the biologically relevant gene interactions of cooperation (sum of mRNA expression), competition (difference between mRNA expression), redundancy (maximum of expression), or dependency (minimum of expression) among the expression levels. The proposed framework identifies dysregulated interactions and pathways enriched in dysregulated interactions; points out interactions that are perturbed across pathways; and moreover, based on the biological annotation of each type of dysregulated interaction gives clues about the regulatory logic governing the systems level perturbation. We demonstrated the potential of GIENA using published datasets related to cancer. Conclusions We showed that GIENA identifies dysregulated pathways that are missed by traditional enrichment methods based on the individual gene properties and that use of traditional methods combined with GIENA provides coverage of the largest number of relevant pathways. In addition

  10. 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. PMID:27581154

  11. 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.

  12. [Care pathways of cancer patients: Modeling and risks analysis induced by oral anticancer drugs].

    PubMed

    Renet, Sophie; Maritaz, Christophe; Lotz, Jean-Pierre; Burnel, Sylvie; Paubel, Pascal

    2016-04-01

    The care pathway of cancer patients is complex and therefore difficult to define. The oral anticancers (AKPO) have shown their benefits to patients and health professionals, however, the risks induced on the care pathway remain unknown. The objective of the study is to define, quantify the risks from AKPO and their effects on the care pathway (breakdown [Ds], rupture [Rt]). From the proposed care pathway model, FMEA method is used to analyze risks. For the 3 identified processes (1 monotherapy, 2 bitherapies: 2 AKPO or 1 AKPO/1 AKIV), analysis revealed an average of 91 risks, 173 Ds, 147 Rt, increased for 1 AKPO/1 AKIV therapy. The administration and delivery are the most risky steps. The lack of training and information of patients and healthcare professionals generates 80% of Ds and Rt. This model confirms the complexity, variability of the care pathway. The development of actions to improve town-hospital coordination and exchange of information is required to optimize and secure the route, confirming the objectives of "Plan Cancer 3". PMID:26891708

  13. 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.

  14. 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.

  15. 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.

  16. Expression analysis of eight amphioxus genes involved in the Wnt/β-catenin signaling pathway

    PubMed Central

    WANG, Jing; LI, Guang; QIAN, Guang-Hui; HUA, Jun-Hao; WANG, Yi-Quan

    2016-01-01

    The Wnt/β-catenin signaling pathway plays a crucial role in the embryonic development of metazoans. Although the pathway has been studied extensively in many model animals, its function in amphioxus, the most primitive chordate, remains largely uncharacterized. To obtain basic data for functional analysis, we identified and isolated seven genes (Lrp5/6, Dvl, APC, CkIα, CkIδ, Gsk3β, and Gro) of the Wnt/β-catenin signaling pathway from the amphioxus (Branchiostoma floridae) genome. Phylogenetic analysis revealed that amphioxus had fewer members of each gene family than that found in vertebrates. Whole-mount in situ hybridization showed that the genes were maternally expressed and broadly distributed throughout the whole embryo at the cleavage and blastula stages. Among them, Dvl was expressed asymmetrically towards the animal pole, while the others were evenly distributed in all blastomeres. At the mid-gastrula stage, the genes were specifically expressed in the primitive endomesoderm, but displayed different patterns. When the embryo developed into the neurula stage, the gene expressions were mainly detected in either paraxial somites or the tail bud. With the development of the embryo, the expression levels further decreased gradually and remained only in some pharyngeal regions or the tail bud at the larva stage. Our results suggest that the Wnt/β-catenin pathway might be involved in amphioxus somite formation and posterior growth, but not in endomesoderm specification. PMID:27265651

  17. 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

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

    PubMed

    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

  19. 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

  20. Expression analysis of eight amphioxus genes involved in the Wnt/β-catenin signaling pathway.

    PubMed

    Wang, Jing; Li, Guang; Qian, Guang-Hui; Hua, Jun-Hao; Wang, Yi-Quan

    2016-05-18

    The Wnt/β-catenin signaling pathway plays a crucial role in the embryonic development of metazoans. Although the pathway has been studied extensively in many model animals, its function in amphioxus, the most primitive chordate, remains largely uncharacterized. To obtain basic data for functional analysis, we identified and isolated seven genes (Lrp5/6, Dvl, APC, CkIα, CkIδ, Gsk3β, and Gro) of the Wnt/β-catenin signaling pathway from the amphioxus (Branchiostoma floridae) genome. Phylogenetic analysis revealed that amphioxus had fewer members of each gene family than that found in vertebrates. Whole-mount in situ hybridization showed that the genes were maternally expressed and broadly distributed throughout the whole embryo at the cleavage and blastula stages. Among them, Dvl was expressed asymmetrically towards the animal pole, while the others were evenly distributed in all blastomeres. At the mid-gastrula stage, the genes were specifically expressed in the primitive endomesoderm, but displayed different patterns. When the embryo developed into the neurula stage, the gene expressions were mainly detected in either paraxial somites or the tail bud. With the development of the embryo, the expression levels further decreased gradually and remained only in some pharyngeal regions or the tail bud at the larva stage. Our results suggest that the Wnt/β-catenin pathway might be involved in amphioxus somite formation and posterior growth, but not in endomesoderm specification. PMID:27265651

  1. CAVER 3.0: a tool for the analysis of transport pathways in dynamic protein structures.

    PubMed

    Chovancova, Eva; Pavelka, Antonin; Benes, Petr; Strnad, Ondrej; Brezovsky, Jan; Kozlikova, Barbora; Gora, Artur; Sustr, Vilem; Klvana, Martin; Medek, Petr; Biedermannova, Lada; Sochor, Jiri; Damborsky, Jiri

    2012-01-01

    Tunnels and channels facilitate the transport of small molecules, ions and water solvent in a large variety of proteins. Characteristics of individual transport pathways, including their geometry, physico-chemical properties and dynamics are instrumental for understanding of structure-function relationships of these proteins, for the design of new inhibitors and construction of improved biocatalysts. CAVER is a software tool widely used for the identification and characterization of transport pathways in static macromolecular structures. Herein we present a new version of CAVER enabling automatic analysis of tunnels and channels in large ensembles of protein conformations. CAVER 3.0 implements new algorithms for the calculation and clustering of pathways. A trajectory from a molecular dynamics simulation serves as the typical input, while detailed characteristics and summary statistics of the time evolution of individual pathways are provided in the outputs. To illustrate the capabilities of CAVER 3.0, the tool was applied for the analysis of molecular dynamics simulation of the microbial enzyme haloalkane dehalogenase DhaA. CAVER 3.0 safely identified and reliably estimated the importance of all previously published DhaA tunnels, including the tunnels closed in DhaA crystal structures. Obtained results clearly demonstrate that analysis of molecular dynamics simulation is essential for the estimation of pathway characteristics and elucidation of the structural basis of the tunnel gating. CAVER 3.0 paves the way for the study of important biochemical phenomena in the area of molecular transport, molecular recognition and enzymatic catalysis. The software is freely available as a multiplatform command-line application at http://www.caver.cz. PMID:23093919

  2. Pathways and Networks-Based Analysis of Candidate Genes Associated with Nicotine Addiction

    PubMed Central

    Liu, Meng; Fan, Rui; Liu, Xinhua; Cheng, Feng; Wang, Ju

    2015-01-01

    Nicotine is the addictive substance in tobacco and it has a broad impact on both the central and peripheral nervous systems. Over the past decades, an increasing number of genes potentially involved in nicotine addiction have been identified by different technical approaches. However, the molecular mechanisms underlying nicotine addiction remain largely unclear. Under such situation, a comprehensive analysis focusing on the overall functional characteristics of these genes, as well as how they interact with each other will provide us valuable information to understand nicotine addiction. In this study, we presented a systematic analysis on nicotine addiction-related genes to identify the major underlying biological themes. Functional analysis revealed that biological processes and biochemical pathways related to neurodevelopment, immune system and metabolism were significantly enriched in the nicotine addiction-related genes. By extracting the nicotine addiction-specific subnetwork, a number of novel genes associated with addiction were identified. Moreover, we constructed a schematic molecular network for nicotine addiction via integrating the pathways and network, providing an intuitional view to understand the development of nicotine addiction. Pathway and network analysis indicated that the biological processes related to nicotine addiction were complex. Results from our work may have important implications for understanding the molecular mechanism underlying nicotine addiction. PMID:25965070

  3. 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

  4. 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

  5. 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.

  6. 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.

  7. 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.

  8. 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

  9. 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. PMID:25901845

  10. Flux Balance Analysis of Mycolic Acid Pathway: Targets for Anti-Tubercular Drugs

    PubMed Central

    Raman, Karthik; Rajagopalan, Preethi; Chandra, Nagasuma

    2005-01-01

    Mycobacterium tuberculosis is the focus of several investigations for design of newer drugs, as tuberculosis remains a major epidemic despite the availability of several drugs and a vaccine. Mycobacteria owe many of their unique qualities to mycolic acids, which are known to be important for their growth, survival, and pathogenicity. Mycolic acid biosynthesis has therefore been the focus of a number of biochemical and genetic studies. It also turns out to be the pathway inhibited by front-line anti-tubercular drugs such as isoniazid and ethionamide. Recent years have seen the emergence of systems-based methodologies that can be used to study microbial metabolism. Here, we seek to apply insights from flux balance analyses of the mycolic acid pathway (MAP) for the identification of anti-tubercular drug targets. We present a comprehensive model of mycolic acid synthesis in the pathogen M. tuberculosis involving 197 metabolites participating in 219 reactions catalysed by 28 proteins. Flux balance analysis (FBA) has been performed on the MAP model, which has provided insights into the metabolic capabilities of the pathway. In silico systematic gene deletions and inhibition of InhA by isoniazid, studied here, provide clues about proteins essential for the pathway and hence lead to a rational identification of possible drug targets. Feasibility studies using sequence analysis of the M. tuberculosis H37Rv and human proteomes indicate that, apart from the known InhA, potential targets for anti-tubercular drug design are AccD3, Fas, FabH, Pks13, DesA1/2, and DesA3. Proteins identified as essential by FBA correlate well with those previously identified experimentally through transposon site hybridisation mutagenesis. This study demonstrates the application of FBA for rational identification of potential anti-tubercular drug targets, which can indeed be a general strategy in drug design. The targets, chosen based on the critical points in the pathway, form a ready shortlist

  11. 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

  12. 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)

  13. 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.

  14. 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. PMID:22653036

  15. 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. PMID:26035432

  16. Bioinformatics analysis of the serine and glycine pathway in cancer cells

    PubMed Central

    Morello, Maria; Minieri, Marilena; Melino, Gerry; Amelio, Ivano

    2014-01-01

    Serine and glycine are amino acids that provide the essential precursors for the synthesis of proteins, nucleic acids and lipids. Employing 3 subsequent enzymes, phosphoglycerate dehydrogenase (PHGDH), phosphoserine phosphatase (PSPH), phosphoserine aminotransferase 1 (PSAT1), 3-phosphoglycerate from glycolysis can be converted in serine, which in turn can by converted in glycine by serine methyl transferase (SHMT). Besides proving precursors for macromolecules, serine/glycine biosynthesis is also required for the maintenance of cellular redox state. Therefore, this metabolic pathway has a pivotal role in proliferating cells, including cancer cells. In the last few years an emerging literature provides genetic and functional evidences that hyperactivation of serine/glycine biosynthetic pathway drives tumorigenesis. Here, we extend these observations performing a bioinformatics analysis using public cancer datasets. Our analysis highlighted the relevance of PHGDH and SHMT2 expression as prognostic factor for breast cancer, revealing a substantial ability of these enzymes to predict patient survival outcome. However analyzing patient datasets of lung cancer our analysis reveled that some other enzymes of the pathways, rather than PHGDH, might be associated to prognosis. Although these observations require further investigations they might suggest a selective requirement of some enzymes in specific cancer types, recommending more cautions in the development of novel translational opportunities and biomarker identification of human cancers. PMID:25436979

  17. 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.

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

    DOE PAGESBeta

    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

  19. 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.

  20. Bioinformatics analysis of differentially expressed pathways related to the metastatic characteristics of osteosarcoma.

    PubMed

    Sun, Wei; Ma, Xiaojun; Shen, Jiakang; Yin, Fei; Wang, Chongren; Cai, Zhengdong

    2016-08-01

    In this study, gene expression data of osteosarcoma (OSA) were analyzed to identify metastasis-related biological pathways. Four gene expression data sets (GSE21257, GSE9508, GSE49003 and GSE66673) were downloaded from Gene Expression Omnibus (GEO). An analysis of differentially expressed genes (DEGs) was performed using the Significance Analysis of Microarray (SAM) method. Gene expression levels were converted into scores of pathways by the Functional Analysis of Individual Microarray Expression (FAIME) algorithm and the differentially expressed pathways (DEPs) were then disclosed by a t-test. The distinguishing and prediction ability of the DEPs for metastatic and non-metastatic OSA was further confirmed using the principal component analysis (PCA) method and 3 gene expression data sets (GSE9508, GSE49003 and GSE66673) based on the support vector machines (SVM) model. A total of 616 downregulated and 681 upregulated genes were identified in the data set, GSE21257. The DEGs could not be used to distinguish metastatic OSA from non-metastatic OSA, as shown by PCA. Thus, an analysis of DEPs was further performed, resulting in 14 DEPs, such as NRAS signaling, Toll-like receptor (TLR) signaling, matrix metalloproteinase (MMP) regulation of cytokines and tumor necrosis factor receptor-associated factor (TRAF)-mediated interferon regulatory factor 7 (IRF7) activation. Cluster analysis indicated that these pathways could be used to distinguish between metastatic OSA from non-metastatic OSA. The prediction accuracy was 91, 66.7 and 87.5% for the data sets, GSE9508, GSE49003 and GSE66673, respectively. The results of PCA further validated that the DEPs could be used to distinguish metastatic OSA from non-metastatic OSA. On the whole, several DEPs were identified in metastatic OSA compared with non-metastatic OSA. Further studies on these pathways and relevant genes may help to enhance our understanding of the molecular mechanisms underlying metastasis

  1. ANALYSIS OF MEASUREMENT UNCERTAINTIES IN THE NULLING TEST FOR AIR LEAKAGE FROM RESIDENTIAL DUCTS.

    SciTech Connect

    ANDREWS,J.W.

    2001-04-01

    An analysis of measurement uncertainties in a recently proposed method of measuring air leakage in residential duct systems has been carried out. The uncertainties in supply and return leakage rates are expressed in terms of the value of the envelope leakage flow coefficient and the uncertainties in measured pressures and air flow rates. Results of the analysis are compared with data published by two research groups.

  2. AIR INGRESS ANALYSIS: PART 2 – COMPUTATIONAL FLUID DYNAMIC MODELS

    SciTech Connect

    Chang H. Oh; Eung S. Kim; Richard Schultz; Hans Gougar; David Petti; Hyung S. Kang

    2011-01-01

    The Idaho National Laboratory (INL), under the auspices of the U.S. Department of Energy, is performing research and development that focuses on key phenomena important during potential scenarios that may occur in very high temperature reactors (VHTRs). Phenomena Identification and Ranking Studies to date have ranked an air ingress event, following on the heels of a VHTR depressurization, as important with regard to core safety. Consequently, the development of advanced air ingress-related models and verification and validation data are a very high priority. Following a loss of coolant and system depressurization incident, air will enter the core of the High Temperature Gas Cooled Reactor through the break, possibly causing oxidation of the in-the core and reflector graphite structure. Simple core and plant models indicate that, under certain circumstances, the oxidation may proceed at an elevated rate with additional heat generated from the oxidation reaction itself. Under postulated conditions of fluid flow and temperature, excessive degradation of the lower plenum graphite can lead to a loss of structural support. Excessive oxidation of core graphite can also lead to the release of fission products into the confinement, which could be detrimental to a reactor safety. Computational fluid dynamic model developed in this study will improve our understanding of this phenomenon. This paper presents two-dimensional and three-dimensional CFD results for the quantitative assessment of the air ingress phenomena. A portion of results of the density-driven stratified flow in the inlet pipe will be compared with results of the experimental results.

  3. 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.

  4. 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

  5. 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

    2014-07-01

    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

  6. Dispersion relation for air via Kramers-Kronig analysis.

    PubMed

    Alvarez, Fernando J; Kuc, Roman

    2008-08-01

    A general expression for the dispersion of acoustic waves in air is obtained by combining the attenuation coefficient given by the ISO:9613-1 standard and the twice-subtracted Kramers-Kronig relation. Good agreement is found with published data of sound velocity at different frequencies and relative humidities. The resulting expression is used to investigate changes in local dispersion with temperature and humidity. PMID:18681503

  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. 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

  9. 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

  10. 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.

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

    PubMed

    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

  12. 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.

  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. PMID:26360871

  14. 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.

  15. Analysis of air pollution from swine production by using air dispersion model and GIS in Quebec.

    PubMed

    Sarr, Joachim H; Goïta, Kalifa; Desmarais, Camille

    2010-01-01

    Swine production, the second most important contributor to Quebec's agricultural revenue, faces many problems. Intensive piggeries, with up to 599 animal units, are used to raise finishing pigs for slaughter. Among the great number of gaseous species emitted to the atmospheric environment from livestock buildings and manure storage units is NH3, which is one of the most important and most offensive with respect to human health. Under appropriate meteorological and topographical conditions, gaseous contaminants can spread and cause a public nuisance--up to a 1-km radius around the farm. To mitigate these effects, the Quebec Government adopted regulations that set minimum buffer distances to be observed by any expansion of an existing or new pig farm. The objectives of this study were (i) to assess the efficiency of the current buffer distance prescriptions in Quebec in mitigating effects of air pollution from swine units and (ii) to identify potential areas for establishing pig farm operations that will not be offensive to people. The air dispersion American Meteorological Society/Environmental Protection Agency Regulatory Model (AERMOD) with receptors distributed at 1.6 km around each source was used first, followed by a spatial geographic information system (GIS) model. Results from the dispersion model showed that the highest hourly concentration with a 99.5% compliance frequency for a single farm was 3078.1 microg/m3 and exceeded the NH3 odor criterion hourly standard set by the Quebec Government at 183.4 microg/m3. Thus, for public safety, densely populated areas like housing developments must be located >1300 m from a pig farm. This distance is in the range of setback distances (723 to 1447 m) obtained by using abacuses defined in the L'Erable Regional County Municipality. That is why we can say the current rules established by the Quebec Government, if rigorously applied, can prevent odor nuisance, due to NH3 emission, from swine farms. In the spatial model

  16. 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.

  17. 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.

  18. Genome-wide association and pathway analysis of feed efficiency in pigs reveal candidate genes and pathways for residual feed intake

    PubMed Central

    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

  19. Integrated pathway analysis of nasopharyngeal carcinoma implicates the axonemal dynein complex in the Malaysian cohort.

    PubMed

    Chin, Yoon-Ming; Tan, Lu Ping; Abdul Aziz, Norazlin; Mushiroda, Taisei; Kubo, Michiaki; Mohd Kornain, Noor Kaslina; Tan, Geok Wee; Khoo, Alan Soo-Beng; Krishnan, Gopala; Pua, Kin-Choo; Yap, Yoke-Yeow; Teo, Soo-Hwang; Lim, Paul Vey-Hong; Nakamura, Yusuke; Lum, Chee Lun; Ng, Ching-Ching

    2016-10-15

    Nasopharyngeal carcinoma (NPC) is an epithelial squamous cell carcinoma on the mucosal lining of the nasopharynx. The etiology of NPC remains elusive despite many reported studies. Most studies employ a single platform approach, neglecting the cumulative influence of both the genome and transcriptome toward NPC development. We aim to employ an integrated pathway approach to identify dysregulated pathways linked to NPC. Our approach combines imputation NPC GWAS data from a Malaysian cohort as well as published expression data GSE12452 from both NPC and non-NPC nasopharynx tissues. Pathway association for GWAS data was performed using MAGENTA while for expression data, GSA-SNP was used with gene p values derived from differential expression values from GEO2R. Our study identified NPC association in the gene ontology (GO) axonemal dynein complex pathway (pGWAS-GSEA  = 1.98 × 10(-2) ; pExpr-GSEA  = 1.27 × 10(-24) ; pBonf-Combined  = 4.15 × 10(-21) ). This association was replicated in a separate cohort using gene expression data from NPC and non-NPC nasopharynx tissues (pAmpliSeq-GSEA  = 6.56 × 10(-4) ). Loss of function in the axonemal dynein complex causes impaired cilia function, leading to poor mucociliary clearance and subsequently upper or lower respiratory tract infection, the former of which includes the nasopharynx. Our approach illustrates the potential use of integrated pathway analysis in detecting gene sets involved in the development of NPC in the Malaysian cohort. PMID:27236004

  20. Global transcriptome analysis reveals circadian regulation of key pathways in plant growth and development

    PubMed Central

    Covington, Michael F; Maloof, Julin N; Straume, Marty; Kay, Steve A; Harmer, Stacey L

    2008-01-01

    Background As nonmotile organisms, plants must rapidly adapt to ever-changing environmental conditions, including those caused by daily light/dark cycles. One important mechanism for anticipating and preparing for such predictable changes is the circadian clock. Nearly all organisms have circadian oscillators that, when they are in phase with the Earth's rotation, provide a competitive advantage. In order to understand how circadian clocks benefit plants, it is necessary to identify the pathways and processes that are clock controlled. Results We have integrated information from multiple circadian microarray experiments performed on Arabidopsis thaliana in order to better estimate the fraction of the plant transcriptome that is circadian regulated. Analyzing the promoters of clock-controlled genes, we identified circadian clock regulatory elements correlated with phase-specific transcript accumulation. We have also identified several physiological pathways enriched for clock-regulated changes in transcript abundance, suggesting they may be modulated by the circadian clock. Conclusion Our analysis suggests that transcript abundance of roughly one-third of expressed A. thaliana genes is circadian regulated. We found four promoter elements, enriched in the promoters of genes with four discrete phases, which may contribute to the time-of-day specific changes in the transcript abundance of these genes. Clock-regulated genes are over-represented among all of the classical plant hormone and multiple stress response pathways, suggesting that all of these pathways are influenced by the circadian clock. Further exploration of the links between the clock and these pathways will lead to a better understanding of how the circadian clock affects plant growth and leads to improved fitness. PMID:18710561

  1. Pulmonary Aluminosis Diagnosed with In-air Microparticle Induced X-ray Emission Analysis of Particles.

    PubMed

    Chino, Haruka; Hagiwara, Eri; Sugisaki, Midori; Baba, Tomonori; Koga, Yasuhiko; Hisada, Takeshi; Kaira, Kyoichi; Okudela, Koji; Takemura, Tamiko; Dobashi, Kunio; Ogura, Takashi

    2015-01-01

    We herein present a case of pulmonary aluminosis diagnosed with in-air microparticle induced X-ray emission (in-air micro-PIXE) analysis. The diagnosis of pulmonary aluminosis was supported by the occupational exposure to aluminum, ground glass opacity and ill-defined centrilobular nodular opacities seen in high resolution CT, and respiratory bronchioles accompanied by pigmented dust by histological examination by in-air micro-PIXE analysis of the lung tissues. The possibility of developing this rare condition should not be underestimated in workers at high-risk jobs. This is an important report showing the usefulness of an in-air micro-PIXE analysis for the early diagnosis of aluminosis. PMID:26278298

  2. 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. PMID:27208995

  3. Genome-Wide Association Study and Pathway-Level Analysis of Tocochromanol Levels in Maize Grain

    PubMed Central

    Lipka, Alexander E.; Gore, Michael A.; Magallanes-Lundback, Maria; Mesberg, Alex; Lin, Haining; Tiede, Tyler; Chen, Charles; Buell, C. Robin; Buckler, Edward S.; Rocheford, Torbert; DellaPenna, Dean

    2013-01-01

    Tocopherols and tocotrienols, collectively known as tocochromanols, are the major lipid-soluble antioxidants in maize (Zea mays L.) grain. Given that individual tocochromanols differ in their degree of vitamin E activity, variation for tocochromanol composition and content in grain from among diverse maize inbred lines has important nutritional and health implications for enhancing the vitamin E and antioxidant contents of maize-derived foods through plant breeding. Toward this end, we conducted a genome-wide association study of six tocochromanol compounds and 14 of their sums, ratios, and proportions with a 281 maize inbred association panel that was genotyped for 591,822 SNP markers. In addition to providing further insight into the association between ZmVTE4 (γ-tocopherol methyltransferase) haplotypes and α-tocopherol content, we also detected a novel association between ZmVTE1 (tocopherol cyclase) and tocotrienol composition. In a pathway-level analysis, we assessed the genetic contribution of 60 a priori candidate genes encoding the core tocochromanol pathway (VTE genes) and reactions for pathways supplying the isoprenoid tail and aromatic head group of tocochromanols. This analysis identified two additional genes, ZmHGGT1 (homogentisate geranylgeranyltransferase) and one prephenate dehydratase parolog (of four in the genome) that also modestly contribute to tocotrienol variation in the panel. Collectively, our results provide the most favorable ZmVTE4 haplotype and suggest three new gene targets for increasing vitamin E and antioxidant levels through marker-assisted selection. PMID:23733887

  4. 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

  5. Chemical pathway analysis of the lower Martian atmosphere: The CO2 stability problem

    NASA Astrophysics Data System (ADS)

    Stock, J. W.; Grenfell, J. L.; Lehmann, R.; Patzer, A. B. C.; Rauer, H.

    2012-08-01

    The chemical composition and hence the structure of terrestrial planetary atmospheres can be critically controlled by trace species which can act in catalytic cycles. Identifying such chemical pathways is in general challenging. Due to the complexity of chemical reaction networks, like those used in Martian atmospheric chemistry, automated methods become more and more useful to cope with this task. Here, we investigate the applicability of a unique analysis tool PAP (Pathway Analysis Program) to the chemistry at Mars' atmospheric surface conditions, for which we have developed a photochemical box-model. PAP is applied for the first time to the output of this model to investigate the well-known CO2 stability problem of the Martian atmosphere. We identify and rank the most dominant pathways responsible for CO2 formation and prove thereby the applicability of PAP for Mars atmospheric conditions by comparison with known chemical cycles. Furthermore, we propose here an additional new catalytic CO2 formation cycle which is also involved in the production of ozone.

  6. 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.

  7. Visual analysis of the air pollution problem in Hong Kong.

    PubMed

    Qu, Huamin; Chan, Wing-Yi; Xu, Anbang; Chung, Kai-Lun; Lau, Kai-Hon; Guo, Ping

    2007-01-01

    We present a comprehensive system for weather data visualization. Weather data are multivariate and contain vector fields formed by wind speed and direction. Several well-established visualization techniques such as parallel coordinates and polar systems are integrated into our system. We also develop various novel methods, including circular pixel bar charts embedded into polar systems, enhanced parallel coordinates with S-shape axis, and weighted complete graphs. Our system was used to analyze the air pollution problem in Hong Kong and some interesting patterns have been found. PMID:17968091

  8. Joint GWAS Analysis: Comparing similar GWAS at different genomic resolutions identifies novel pathway associations with six complex diseases

    PubMed Central

    McGeachie, Michael J.; Clemmer, George L.; Lasky-Su, Jessica; Dahlin, Amber; Raby, Benjamin A.; Weiss, Scott T.

    2014-01-01

    We show here that combining two existing genome wide association studies (GWAS) yields additional biologically relevant information, beyond that obtained by either GWAS separately. We propose Joint GWAS Analysis, a method that compares a pair of GWAS for similarity among the top SNP associations, top genes identified, gene functional clusters, and top biological pathways. We show that Joint GWAS Analysis identifies additional enriched biological pathways that would be missed by traditional Single-GWAS analysis. Furthermore, we examine the similarities of six complex genetic disorders at the SNP-level, gene-level, gene-cluster-level, and pathway-level. We make concrete hypotheses regarding novel pathway associations for several complex disorders considered, based on the results of Joint GWAS Analysis. Together, these results demonstrate that common complex disorders share substantially more genomic architecture than has been previously realized and that the meta-analysis of GWAS needs not be limited to GWAS of the same phenotype to be informative. PMID:25838990

  9. Analysis of Tumor Suppressor Genes Based on Gene Ontology and the KEGG Pathway

    PubMed Central

    Kong, Xiangyin; Huang, Tao; Cai, Yu-Dong

    2014-01-01

    Cancer is a serious disease that causes many deaths every year. We urgently need to design effective treatments to cure this disease. Tumor suppressor genes (TSGs) are a type of gene that can protect cells from becoming cancerous. In view of this, correct identification of TSGs is an alternative method for identifying effective cancer therapies. In this study, we performed gene ontology (GO) and pathway enrichment analysis of the TSGs and non-TSGs. Some popular feature selection methods, including minimum redundancy maximum relevance (mRMR) and incremental feature selection (IFS), were employed to analyze the enrichment features. Accordingly, some GO terms and KEGG pathways, such as biological adhesion, cell cycle control, genomic stability maintenance and cell death regulation, were extracted, which are important factors for identifying TSGs. We hope these findings can help in building effective prediction methods for identifying TSGs and thereby, promoting the discovery of effective cancer treatments. PMID:25207935

  10. Change point analysis of mean annual air temperature in Iran

    NASA Astrophysics Data System (ADS)

    Shirvani, A.

    2015-06-01

    The existence of change point in the mean of air temperature is an important indicator of climate change. In this study, Student's t parametric and Mann-Whitney nonparametric Change Point Models (CPMs) were applied to test whether a change point has occurred in the mean of annual Air Temperature Anomalies Time Series (ATATS) of 27 synoptic stations in different regions of Iran for the period 1956-2010. The Likelihood Ratio Test (LRT) was also applied to evaluate the detected change points. The ATATS of all stations except Bandar Anzali and Gorgan stations, which were serially correlated, were transformed to produce an uncorrelated pre-whitened time series as an input file for the CPMs and LRT. Both the Student's t and Mann-Whitney CPMs detected the change point in the ATATS of (a) Tehran Mehrabad, Abadan, Kermanshah, Khoramabad and Yazd in 1992, (b) Mashhad and Tabriz in 1993, (c) Bandar Anzali, Babolsar and Ramsar in 1994, (d) Kerman and Zahedan in 1996 at 5% significance level. The likelihood ratio test shows that the ATATS before and after detected change points in these 12 stations are normally distributed with different means. The Student's t and Mann-Whitney CPMs suggested different change points for individual stations in Bushehr, Bam, Shahroud, and Gorgan. However, the LRT confirmed the change points in these four stations as 1997, 1996, 1993, and 1996, respectively. No change points were detected in the remaining 11 stations.

  11. Global Proteomics and Pathway Analysis of Pressure-overload Induced Heart Failure and Its Attenuation by Mitochondrial Targeted Peptides

    PubMed Central

    Dai, Dao-Fu; Hsieh, Edward J.; Chen, Tony; Menendez, Lorena G.; Basisty, Nathan B.; Tsai, Lauren; Beyer, Richard P.; Crispin, David A.; Shulman, Nicholas J.; Szeto, Hazel H.; Tian, Rong; MacCoss, Michael J.; Rabinovitch, Peter S.

    2013-01-01

    Background We investigated the protective effects of mitochondrial-targeted antioxidant and protective peptides, SS31 and SS20, on cardiac function, proteomic remodeling and signaling pathways. Methods and Results We applied an improved label-free shotgun proteomics approach to evaluate the global proteomics changes in transverse aortic constriction (TAC) induced heart failure, and the associated signaling pathway changes using Ingenuity Pathway Analysis (IPA). We found 538 proteins significantly changed after TAC, which mapped to 53 pathways. The top pathways were in the categories of actin cytoskeleton, mitochondrial function, intermediate metabolism, glycolysis / gluconeogenesis and citrate cycle. Concomitant treatment with SS31 ameliorated the congestive heart failure phenotypes and mitochondrial damage induced by TAC, in parallel with global attenuation of mitochondrial proteome changes, with an average of 84% protection of mitochondrial and 69% of non-mitochondrial protein changes. This included significant amelioration of All the IPA pathways noted above. SS20 had only modest effects on heart failure and this tracked with only partial attenuation of global proteomics changes; furthermore, while actin cytoskeleton pathways were significantly protected in SS20, mitochondrial and metabolic pathways essentially were not. Conclusions This study elucidates the signaling pathways significantly changed in pressure-overload induced heart failure. The global attenuation of TAC-induced proteomic alterations by the mitochondrial targeted peptide SS-31 suggests that perturbed mitochondrial function may be an upstream signal to many of pathway alterations in TAC and supports the potential clinical application of mitochondrial-targeted peptide drugs for the treatment heart failure. PMID:23935006

  12. Human and chicken TLR pathways: manual curation and computer-based orthology analysis

    PubMed Central

    Gillespie, Marc; Shamovsky, Veronica; D’Eustachio, Peter

    2011-01-01

    The innate immune responses mediated by Toll-like receptors (TLR) provide an evolutionarily well-conserved first line of defense against microbial pathogens. In the Reactome Knowledgebase we previously integrated annotations of human TLR molecular functions with those of over 4000 other human proteins involved in processes such as adaptive immunity, DNA replication, signaling, and intermediary metabolism, and have linked these annotations to external resources, including PubMed, UniProt, EntrezGene, Ensembl, and the Gene Ontology to generate a resource suitable for data mining, pathway analysis, and other systems biology approaches. We have now used a combination of manual expert curation and computer-based orthology analysis to generate a set of annotations for TLR molecular function in the chicken (Gallus gallus). Mammalian and avian lineages diverged approximately 300 million years ago, and the avian TLR repertoire consists of both orthologs and distinct new genes. The work described here centers on the molecular biology of TLR3, the host receptor that mediates responses to viral and other doubled-stranded polynucleotides, as a paradigm for our approach to integrated manual and computationally based annotation and data analysis. It tests the quality of computationally generated annotations projected from human onto other species and supports a systems biology approach to analysis of virus-activated signaling pathways and identification of clinically useful antiviral measures. PMID:21052677

  13. 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

    2015-05-01

    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 ([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. PMID:25758824

  14. 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

  15. 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.

  16. An analysis of Freedman's "image pulse" model in air.

    PubMed

    Tsakiris, J; McKerrow, P

    2000-10-01

    The "image pulse" model developed by Freedman calculates the echoes generated from convex objects in an underwater environment after insonification with a narrow-band transient signal. The model uses the source radiation and the solid angle subtended at the transducer by the scattering body to determine the echo structure. Work has been completed in adapting this model for use in an air environment using noncoincident transmitters and receivers. Experiments were conducted to measure the amplitudes of the echoes off a range of convex objects, at distances up to 1.4 m, after insonification with a Polaroid transducer. These measured amplitudes were compared to those predicted by the model, with the results for cones highlighting the limitations of the model. Spheres, however, performed significantly better, with an average error of under 5%, indicating that the model should be reasonably accurate at calculating the echoes off convex objects with a smoothly varying surface. PMID:11051488

  17. Flow Analysis over Batten Reinforced Wings for Micro Air Vehicles

    NASA Astrophysics Data System (ADS)

    Townsend, Kurtis; Hicks, Travis; Hubner, James P.

    2008-11-01

    Flexible membrane wings modify the flow separation of low Reynolds number micro air vehicles (MAVs). A specific type of fixed-wing geometry is a batten-reinforced configuration in which the membrane is attached to a rigid frame with chordwise battens, allowing the vibration of the membrane at the trailing-edge. In this study, smoke-wire visualization and hot-wire anemometry, both near the trailing-edge and further downstream in the wake, are used to quantify the frequency and energy of these fluctuations for various cell geometries and flow angles-of-attack. Improvement in the wake momentum deficit will be analyzed to determine preferred membrane cell geometries for MAV flight conditions.

  18. Critical radionuclide/critical pathway analysis for the U.S. Department of Energy`s Savannah River Site

    SciTech Connect

    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.

  19. Identification of Common Biological Pathways and Drug Targets Across Multiple Respiratory Viruses Based on Human Host Gene Expression Analysis

    PubMed Central

    Smith, Steven B.; Dampier, William; Tozeren, Aydin; Brown, James R.; Magid-Slav, Michal

    2012-01-01

    Background Pandemic and seasonal respiratory viruses are a major global health concern. Given the genetic diversity of respiratory viruses and the emergence of drug resistant strains, the targeted disruption of human host-virus interactions is a potential therapeutic strategy for treating multi-viral infections. The availability of large-scale genomic datasets focused on host-pathogen interactions can be used to discover novel drug targets as well as potential opportunities for drug repositioning. Methods/Results In this study, we performed a large-scale analysis of microarray datasets involving host response to infections by influenza A virus, respiratory syncytial virus, rhinovirus, SARS-coronavirus, metapneumonia virus, coxsackievirus and cytomegalovirus. Common genes and pathways were found through a rigorous, iterative analysis pipeline where relevant host mRNA expression datasets were identified, analyzed for quality and gene differential expression, then mapped to pathways for enrichment analysis. Possible repurposed drugs targets were found through database and literature searches. A total of 67 common biological pathways were identified among the seven different respiratory viruses analyzed, representing fifteen laboratories, nine different cell types, and seven different array platforms. A large overlap in the general immune response was observed among the top twenty of these 67 pathways, adding validation to our analysis strategy. Of the top five pathways, we found 53 differentially expressed genes affected by at least five of the seven viruses. We suggest five new therapeutic indications for existing small molecules or biological agents targeting proteins encoded by the genes F3, IL1B, TNF, CASP1 and MMP9. Pathway enrichment analysis also identified a potential novel host response, the Parkin-Ubiquitin Proteasomal System (Parkin-UPS) pathway, which is known to be involved in the progression of neurodegenerative Parkinson's disease. Conclusions Our study

  20. 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.

  1. Pathologic Analysis of Control Plans for Air Pollution Management in Tehran Metropolis: A Qualitative Study

    PubMed Central

    Shahrabi, Narges Salehi; Pourezzat, Aliasghar; Fayaz-Bakhsh, Ahmad; Mafimoradi, Shiva; Poursafa, Parinaz

    2013-01-01

    Background: Regarding the importance of air pollution issue for large cities, as Tehran metropolis, many plans, programs, projects and regulations have been developed to manage urban air pollution. However, most of them failed to decline the pollution. The purpose of this study is to pathologically analyze air-pollution control plans in order to offer effective solutions for Tehran metropolis. Methods: A qualitative content analysis and a semi-structured interview with 14 practicing professionals were used to identify key causes and sources of Tehran's air pollution, to recognize challenges and obstacles towards effective performance of air-pollution control plans in this metropolitan area, and to suggest the most effective controlling solutions. Results: Challenges related to air-pollution control plans can be divided into two major categories: Firstly lack of integrated and organized stewardship and secondly those related to political, economical, social and technical environmental abbreviated as PEST, challenges. For effective control of the Tehran air pollution, the following eight controlling alternatives were identified: Systematization of plan preparation process, organizing the stewardship, standardization and utilization of new technologies and professional experts, cultural and infrastructural development, realization of social justice, developing coordination and controlling mechanisms, improving citizen's participatory capacity, and focusing on effective management of fuel and energy. Conclusions: Controlling air pollution in Tehran should be considered as a priority for policymakers to make enforcements through applying a systemic cycle of preparation effective and comprehensive plans. Further, implement the enforcements and evaluate the environmental impact of the plans through involving all stakeholders. PMID:24130939

  2. Forecasting of Air Quality Index in Delhi Using Neural Network Based on Principal Component Analysis

    NASA Astrophysics Data System (ADS)

    Kumar, Anikender; Goyal, P.

    2013-04-01

    Forecasting of the air quality index (AQI) is one of the topics of air quality research today as it is useful to assess the effects of air pollutants on human health in urban areas. It has been learned in the last decade that airborne pollution has been a serious and will be a major problem in Delhi in the next few years. The air quality index is a number, based on the comprehensive effect of concentrations of major air pollutants, used by Government agencies to characterize the quality of the air at different locations, which is also used for local and regional air quality management in many metro cities of the world. Thus, the main objective of the present study is to forecast the daily AQI through a neural network based on principal component analysis (PCA). The AQI of criteria air pollutants has been forecasted using the previous day's AQI and meteorological variables, which have been found to be nearly same for weekends and weekdays. The principal components of a neural network based on PCA (PCA-neural network) have been computed using a correlation matrix of input data. The evaluation of the PCA-neural network model has been made by comparing its results with the results of the neural network and observed values during 2000-2006 in four different seasons through statistical parameters, which reveal that the PCA-neural network is performing better than the neural network in all of the four seasons.

  3. Gene set enrichment analysis and ingenuity pathway analysis of metastatic clear cell renal cell carcinoma cell line.

    PubMed

    Khan, Mohammed I; Dębski, Konrad J; Dabrowski, Michał; Czarnecka, Anna M; Szczylik, Cezary

    2016-08-01

    In recent years, genome-wide RNA expression analysis has become a routine tool that offers a great opportunity to study and understand the key role of genes that contribute to carcinogenesis. Various microarray platforms and statistical approaches can be used to identify genes that might serve as prognostic biomarkers and be developed as antitumor therapies in the future. Metastatic renal cell carcinoma (mRCC) is a serious, life-threatening disease, and there are few treatment options for patients. In this study, we performed one-color microarray gene expression (4×44K) analysis of the mRCC cell line Caki-1 and the healthy kidney cell line ASE-5063. A total of 1,921 genes were differentially expressed in the Caki-1 cell line (1,023 upregulated and 898 downregulated). Gene Set Enrichment Analysis (GSEA) and Ingenuity Pathway Analysis (IPA) approaches were used to analyze the differential-expression data. The objective of this research was to identify complex biological changes that occur during metastatic development using Caki-1 as a model mRCC cell line. Our data suggest that there are multiple deregulated pathways associated with metastatic clear cell renal cell carcinoma (mccRCC), including integrin-linked kinase (ILK) signaling, leukocyte extravasation signaling, IGF-I signaling, CXCR4 signaling, and phosphoinositol 3-kinase/AKT/mammalian target of rapamycin signaling. The IPA upstream analysis predicted top transcriptional regulators that are either activated or inhibited, such as estrogen receptors, TP53, KDM5B, SPDEF, and CDKN1A. The GSEA approach was used to further confirm enriched pathway data following IPA. PMID:27279483

  4. Design analysis of an aluminum-air battery for vehicle operations. Transportation systems research

    SciTech Connect

    Behrin, E.; Wood, R.L.; Salisbury, J.D.; Whisler, D.J.; Hudson, C.L.

    1983-03-18

    The objective of the study reported was to perform a detailed configuration analysis of an aluminum-air battery, evaluate various automobile propulsion systems utilizing the Al-air battery, and estimate the performance and cost of vehicles incorporating these propulsion systems. A preliminary engineering design is performed. A physical model and a cell-performance model of a conceptual mass-produced Al-air battery were constructed and work together to characterize the battery system. The physical battery model is based on a specific battery design concept and defines the mass and volume of a complete Al-air battery system. The cell-performance model simulates the electrical and electrochemical characteristics of the battery. The physical model and two versions of the cell-performance model - near-term and optimistic - were used in a vehicle-conversion analysis to evaluate three automotive propulsion systems - Al-air battery only, Al-air battery/secondary battery, and Al-air battery/flywheel. (LEW)

  5. 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

  6. 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

  7. Chemical pathway analysis of the Martian atmosphere: The formation and destruction of ozone

    NASA Astrophysics Data System (ADS)

    Stock, Joachim; Boxe, Christopher; Lehmann, Ralph; Grenfell, Lee; Patzer, Beate; Rauer, Heike; Yung, Yuk

    2014-05-01

    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 approximately 40 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 are 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 Mars' 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

  8. Pathway-Based Analysis Using Genome-wide Association Data from a Korean Non-Small Cell Lung Cancer Study

    PubMed Central

    Lee, Donghoon; Lee, Geon Kook; Yoon, Kyong-Ah; Lee, Jin Soo

    2013-01-01

    Pathway-based analysis, used in conjunction with genome-wide association study (GWAS) techniques, is a powerful tool to detect subtle but systematic patterns in genome that can help elucidate complex diseases, like cancers. Here, we stepped back from genetic polymorphisms at a single locus and examined how multiple association signals can be orchestrated to find pathways related to lung cancer susceptibility. We used single-nucleotide polymorphism (SNP) array data from 869 non-small cell lung cancer (NSCLC) cases from a previous GWAS at the National Cancer Center and 1,533 controls from the Korean Association Resource project for the pathway-based analysis. After mapping single-nucleotide polymorphisms to genes, considering their coding region and regulatory elements (±20 kbp), multivariate logistic regression of additive and dominant genetic models were fitted against disease status, with adjustments for age, gender, and smoking status. Pathway statistics were evaluated using Gene Set Enrichment Analysis (GSEA) and Adaptive Rank Truncated Product (ARTP) methods. Among 880 pathways, 11 showed relatively significant statistics compared to our positive controls (PGSEA≤0.025, false discovery rate≤0.25). Candidate pathways were validated using the ARTP method and similarities between pathways were computed against each other. The top-ranked pathways were ABC Transporters (PGSEA<0.001, PARTP = 0.001), VEGF Signaling Pathway (PGSEA<0.001, PARTP = 0.008), G1/S Check Point (PGSEA = 0.004, PARTP = 0.013), and NRAGE Signals Death through JNK (PGSEA = 0.006, PARTP = 0.001). Our results demonstrate that pathway analysis can shed light on post-GWAS research and help identify potential targets for cancer susceptibility. PMID:23762359

  9. Analysis of Exosome Release as a Cellular Response to MAPK Pathway Inhibition

    PubMed Central

    Agarwal, K.; Saji, M.; Lazaroff, S. M.; Palmer, A. F.; Ringel, M. D.; Paulaitis, M. E.

    2015-01-01

    Exosome size distributions and numbers of exosomes released per cell are measured by asymmetric flow-field flow fractionation/multi-angle light scattering (A4F/MALS) for three thyroid cancer cell lines as a function of a treatment that inhibits MAPK signaling pathways in the cells. We show that these cell lines release exosomes with well-defined morphological features and size distributions that reflect a common biological process for their formation and release into the extracellular environment. We find that those cell lines with constitutive activation of the MAPK signaling pathway display MEK-dependent exosome release characterized by increased numbers of exosomes released per cell. Analysis of the measured exosome size distributions based on a generalized extreme value distribution model for exosome formation in intracellular multivesicular bodies highlights the importance of this experimental observable for delineating different mechanisms of vesicle formation and predicting how changes in exosome release can be modified by pathway inhibitors in a cell context-dependent manner. PMID:25915504

  10. Design and analysis of metabolic pathways supporting formatotrophic growth for electricity-dependent cultivation of microbes.

    PubMed

    Bar-Even, Arren; Noor, Elad; Flamholz, Avi; Milo, Ron

    2013-01-01

    Electrosynthesis is a promising approach that enables the biological production of commodities, like fuels and fine chemicals, using renewably produced electricity. Several techniques have been proposed to mediate the transfer of electrons from the cathode to living cells. Of these, the electroproduction of formate as a mediator seems especially promising: formate is readily soluble, of low toxicity and can be produced at relatively high efficiency and at reasonable current density. While organisms that are capable of formatotrophic growth, i.e. growth on formate, exist naturally, they are generally less suitable for bulk cultivation and industrial needs. Hence, it may be helpful to engineer a model organism of industrial relevance, such as E. coli, for growth on formate. There are numerous metabolic pathways that can potentially support formatotrophic growth. Here we analyze these diverse pathways according to various criteria including biomass yield, thermodynamic favorability, chemical motive force, kinetics and the practical challenges posed by their expression. We find that the reductive glycine pathway, composed of the tetrahydrofolate system, the glycine cleavage system, serine hydroxymethyltransferase and serine deaminase, is a promising candidate to support electrosynthesis in E. coli. The approach presented here exemplifies how combining different computational approaches into a systematic analysis methodology provides assistance in redesigning metabolism. This article is part of a Special Issue entitled: Metals in Bioenergetics and Biomimetics Systems. PMID:23123556

  11. Analysis of corkscrew signaling in the Drosophila epidermal growth factor receptor pathway during myogenesis.

    PubMed Central

    Johnson Hamlet, M R; Perkins, L A

    2001-01-01

    The Drosophila nonreceptor protein tyrosine phosphatase, Corkscrew (Csw), functions positively in multiple receptor tyrosine kinase (RTK) pathways, including signaling by the epidermal growth factor receptor (EGFR). Detailed phenotypic analyses of csw mutations have revealed that Csw activity is required in many of the same developmental processes that require EGFR function. However, it is still unclear where in the signaling hierarchy Csw functions relative to other proteins whose activities are also required downstream of the receptor. To address this issue, genetic interaction experiments were performed to place csw gene activity relative to the EGFR, spitz (spi), rhomboid (rho), daughter of sevenless (DOS), kinase-suppressor of ras (ksr), ras1, D-raf, pointed (pnt), and moleskin. We followed the EGFR-dependent formation of VA2 muscle precursor cells as a sensitive assay for these genetic interaction studies. First, we established that Csw has a positive function during mesoderm development. Second, we found that tissue-specific expression of a gain-of-function csw construct rescues loss-of-function mutations in other positive signaling genes upstream of rolled (rl)/MAPK in the EGFR pathway. Third, we were able to infer levels of EGFR signaling in various mutant backgrounds during myogenesis. This work extends previous studies of Csw during Torso and Sevenless RTK signaling to include an in-depth analysis of the role of Csw in the EGFR signaling pathway. PMID:11729154

  12. Structural Stress Analysis on the Rubber Diaphragm of Air-Operated Valve

    NASA Astrophysics Data System (ADS)

    Lee, Young-Shin; Cho, Taik-Dong; Ko, Sung-Ho; Lee, Hyun-Seung; Shin, Sung-Ky

    Air-operated valves are used extensively in the power-generation industry for process control and system isolation functions. A study on the prevention of damage of an air operated valve is very important. Specially, diaphragm in an actuator of an air-operated valve has the highest damage rate. In this study, the stress of diaphragm with thickness change is analyzed. For this analysis, four experiments were conducted to obtain material properties of rubber. A stress analysis is carried out by commercial FEM code, ANSYS 8.0. It is compared with tension test to verify finite element analysis. From the result of analysis, the maximum stress happened at flange edge part, and the maximum displacement happened between flange edge and spring support. This study also finds out effect of the thickness about variable thickness. Even if a section area is same, the maximum stress is varied with the thickness of edge side.

  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. 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.

  15. 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...

  16. In-depth analysis of the critical genes and pathways in colorectal cancer

    PubMed Central

    LIU, FUGUO; JI, FENGZHI; JI, YULING; JIANG, YUEPING; SUN, XUEGUO; LU, YANYAN; ZHANG, LINGYUN; HAN, YUE; LIU, XISHUANG

    2015-01-01

    The present study aimed to investigate the molecular targets for colorectal cancer (CRC). Differentially expressed genes (DEGs) were screened between CRC and matched adjacent noncancerous samples. GENETIC_ASSOIATION_DB_DISEASE analysis was performed to identify CRC genes from the identified DEGs using the Database for Annotation, Visualization and Integrated Discovery, followed by Gene Οntology (GO) and Kyoto Encyclopedia of Genes and Genomes analysis for the CRC genes. A protein-protein interaction (PPI) network was constructed for the CRC genes, followed by determination and analysis of the hub genes, in terms of the protein domains and spatial structure. In total, 35 CRC genes were determined, including 19 upregulated and 16 downregulated genes. Downregulated N-acetyltransferase (NAT)1 and NAT2 were enriched in the caffeine metabolism pathway. The down-regulated and upregulated genes were enriched in a number of GO terms and pathways, respectively. Cyclin D1 (CCND1) and proliferating cell nuclear antigen (PCNA) were identified as the hub genes in the PPI network. The C-terminal and N-terminal domains were similar in PCNA, but different in CCND1. The results suggested PCNA, CCND1, NAT1 and NAT2 for use as biomarkers to enable early diagnosis and monitoring of CRC. These results form a basis for developing therapies, which target the unique protein domains of PCNA and CCND1. PMID:26239303

  17. 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. PMID:23906496

  18. Systems Analysis Unfolds the Relationship between the Phosphoketolase Pathway and Growth in Aspergillus nidulans

    PubMed Central

    Regueira, Torsten B.; Hofmann, Gerald; Nielsen, Jens; Olsson, Lisbeth

    2008-01-01

    Background Aspergillus nidulans is an important model organism for studies on fundamental eukaryotic cell biology and on industrial processes due to its close relation to A. niger and A. oryzae. Here we identified the gene coding for a novel metabolic pathway in A. nidulans, namely the phosphoketolase pathway, and investigated the role of an increased phosphoketolase activity. Methodology/Principal Findings Over-expression of the phosphoketolase gene (phk) improved the specific growth rate on xylose, glycerol and ethanol. Transcriptome analysis showed that a total of 1,222 genes were significantly affected by over-expression of the phk, while more than half of the affected genes were carbon source specific. During growth on glucose medium, the transcriptome analysis showed that the response to phk over-expression is targeted to neutralize the effect of the over-expression by regulating the acetate metabolism and initiate a growth dampening response. Conclusions/Significance Metabolic flux analysis using 13C-labelled glucose, showed that over-expression of phosphoketolase added flexibility to the central metabolism. Our findings further suggests that A. nidulans is not optimized for growth on xylose, glycerol or ethanol as the sole carbon sources. PMID:19052639

  19. Proteomic Analysis Reveals a Novel Mutator S (MutS) Partner Involved in Mismatch Repair Pathway.

    PubMed

    Chen, Zhen; Tran, Mykim; Tang, Mengfan; Wang, Wenqi; Gong, Zihua; Chen, Junjie

    2016-04-01

    The mismatch repair (MMR) family is a highly conserved group of proteins that function in correcting base-base and insertion-deletion mismatches generated during DNA replication. Disruption of this process results in characteristic microsatellite instability (MSI), repair defects, and susceptibility to cancer. However, a significant fraction of MSI-positive cancers express MMR genes at normal levels and do not carry detectable mutation in known MMR genes, suggesting that additional factors and/or mechanisms may exist to explain these MSI phenotypes in patients. To systematically investigate the MMR pathway, we conducted a proteomic analysis and identified MMR-associated protein complexes using tandem-affinity purification coupled with mass spectrometry (TAP-MS) method. The mass spectrometry data have been deposited to the ProteomeXchange with identifier PXD003014 and DOI 10.6019/PXD003014. We identified 230 high-confidence candidate interaction proteins (HCIPs). We subsequently focused on MSH2, an essential component of the MMR pathway and uncovered a novel MSH2-binding partner, WDHD1. We further demonstrated that WDHD1 forms a stable complex with MSH2 and MSH3 or MSH6,i.e.the MutS complexes. The specific MSH2/WDHD1 interaction is mediated by the second lever domain of MSH2 and Ala(1123)site of WDHD1. Moreover, we showed that, just like MSH2-deficient cells, depletion of WDHD1 also led to 6-thioguanine (6-TG) resistance, indicating that WDHD1 likely contributes to the MMR pathway. Taken together, our study uncovers new components involved in the MMR pathway, which provides candidate genes that may be responsible for the development of MSI-positive cancers. PMID:27037360

  20. 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.

  1. NASTRAN analysis of an air storage piping system

    NASA Technical Reports Server (NTRS)

    Young, C. P., Jr.; Gerringer, A. H.; Faison, R. W.

    1973-01-01

    The application of NASTRAN to a complex piping design evaluation problem is summarized. Emphasis is placed on structural modeling aspects, problems encountered in modeling and analyzing curved pipe sections, principal results, and relative merits of using NASTRAN as a pipe analysis and design tool. In addition, the piping and manifolding system was analyzed with SNAP (Structural Network Analysis Program). The parallel SNAP study provides a basis for limited comparisons between NASTRAN and SNAP as to solution agreement and computer execution time and costs.

  2. 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.

  3. Time-series analysis for determining vertical air permeability in unsaturated zones

    SciTech Connect

    Lu, N.

    1999-01-01

    The air pressure in the unsaturated subsurface changes dynamically as the barometric pressure varies with time. Depending on the material properties and boundary conditions, the intensity of the correlation between the atmospheric and subsurface pressures may be evidenced in two persistent patterns: (1) the amplitude attenuation; and (2) the phase lag for the principal modes, such as the diurnal, semidiurnal, and 8-h tides. The amplitude attenuation and the phase lag generally depend on properties that can be classified into two categories: (1) The barometric pressure parameters, such as the apparent pressure amplitudes and frequencies controlled by the atmospheric tides and others; and (2) the material properties of porous media, such as the air viscosity, air-filled porosity, and permeability. Based on the principle of superposition and a Fourier time-series analysis, an analytical solution for predicting the subsurface air pressure variation caused by the atmospheric pressure fluctuation is presented. The air permeability (or pneumatic diffusivity) can be quantitatively determined by using the calculated amplitude attenuations (or phase lags) and the appropriate analytical relations among the parameters of the atmosphere and the porous medium. An analysis using the field data shows that the Fourier time-series analysis may provide a potentially reliable and simple method for predicting the subsurface barometric pressure variation and for determining the air permeability of unsaturated zones.

  4. 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

  5. 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.

  6. 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.

  7. RARE PROJECT: AIR TOXICS DATA ANALYSIS FOR SPATIAL ANALYSIS OF AMBIENT VOCS AT SELECTED CENSUS TRACTS IN HOUSTON-GALVESTON

    EPA Science Inventory

    This is an ORD Regional Applied Research Effort (RARE) study with EPA Region 6 to conduct data analysis geared to spatial analysis for estimation of ambient VOCs at selected census tract areas in Houston-Galveston area. For a better understanding of air toxics impacts in the Hou...

  8. 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

  9. Gene network and canonical pathway analysis in canine myxomatous mitral valve disease: a microarray study.

    PubMed

    Lu, C-C; Liu, M-M; Culshaw, G; Clinton, M; Argyle, D J; Corcoran, B M

    2015-04-01

    Myxomatous mitral valve disease (MMVD) is the single most common acquired heart disease of the dog and is particularly common in small pedigree breed dogs such as the Cavalier King Charles spaniel (CKCS). There are limited data on the mitral valve transcriptome and the aim of this study was to use the microarray technology in conjunction with bioinformatics platforms to analyse transcript changes in MMVD in CKCS compared to normal dogs (non-CKCS). Differentially expressed genes (n = 5397) were identified using cut-off settings of fold change, false discovery rate (FDR) and P <0.05. In total, 4002 genes were annotated to a specific transcript in the Affymetrix canine database, and after further filtering, 591 annotated canine genes were identified: 322 (55%) were up-regulated and 269 (45%) were down-regulated. Canine microRNAs (cfa-miR; n = 59) were also identified. Gene ontology and network analysis platforms identified between six and 10 significantly different biological function clusters from which the following were selected as relevant to MMVD: inflammation, cell movement, cardiovascular development, extracellular matrix organisation and epithelial-to-mesenchymal (EMT) transition. Ingenuity Pathway Analysis identified three canonical pathways relevant to MMVD: caveolar-mediated endocytosis, remodelling of epithelial adherens junctions, and endothelin-1 signalling. Considering the biological relevance to MMVD, the gene families of importance with significant difference between groups included collagens, ADAMTS peptidases, proteoglycans, matrix metalloproteinases (MMPs) and their inhibitors, basement membrane components, cathepsin S, integrins, tight junction cell adhesion proteins, cadherins, other matrix-associated proteins, and members of the serotonin (5-HT)/transforming growth factor -β signalling pathway. PMID:25841900

  10. 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. PMID:22037480

  11. 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

  12. Cost Analysis of Online Courses. AIR 2000 Annual Forum Paper.

    ERIC Educational Resources Information Center

    Milam, John H., Jr.

    This paper presents a complex, hybrid, method of cost analysis of online courses, which incorporates data on expenditures; student/course enrollment; departmental consumption/contribution; space utilization/opportunity costs; direct non-personnel costs; computing support; faculty/staff workload; administrative overhead at the department, dean, and…

  13. 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.

  14. 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

  15. 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

    2016-01-01

    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

  16. 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.

  17. Analysis on the Density Driven Air-Ingress Accident in VHTRs

    SciTech Connect

    Eung Soo Kim; Chang Oh; Richard Schultz; David Petti

    2008-11-01

    Air-ingress following the pipe rupture is considered to be the most serious accident in the VHTRs due to its potential problems such as core heat-up, structural integrity and toxic gas release. Previously, it has been believed that the main air-ingress mechanism of this accident is the molecular diffusion process between the reactor core and the cavity. However, according to some recent studies, there is another fast air-ingress process that has not been considered before. It is called density-driven stratified flow. The potential for density-driven stratified air ingress into the VHTR following a large-break LOCA was first described in the NGNP Methods Technical Program based on stratified flow studies performed with liquid. Studies on densitygradient driven stratified flow in advanced reactor systems has been the subject of active research for well over a decade since density-gradient dominated stratified flow is an inherent characteristic of passive systems used in advanced reactors. Recently, Oh et al. performed a CFD analysis on the stratified flow in the VHTR, and showed that this effect can significantly accelerate the air-ingress process in the VHTRs. They also proposed to replace the original air-ingress scenario based on the molecular diffusion with the one based on the stratified flow. This paper is focusing on the effect of stratified flow on the results of the air-ingress accident in VHTR

  18. Atmospheric Infrared Sounder (AIRS) sounding evaluation and analysis of the pre-convective environment

    NASA Astrophysics Data System (ADS)

    Botes, Danelle; Mecikalski, John R.; Jedlovec, Gary J.

    2012-05-01

    The Atmospheric Infrared Sounder (AIRS) is a hyperspectral instrument onboard the National Aeronautics and Space Administration's (NASA) Earth Observing System (EOS) Aqua satellite. This study investigates the performance of AIRS soundings in characterizing the stability in the pre-convective environment of the southeastern United States. AIRS soundings are collocated with radiosonde observations within ±1 degree and 2 h of the Aqua overpass. For each case, the AIRS sounding with maximum PBest quality indicator (signifying the pressure level above which the sounding is of best quality) is chosen for analysis. Rapid Update Cycle soundings from 1800 UTC analyses are used to evaluate the results from AIRS. Precipitable water and stability indices including convective available potential energy, convective inhibition, Lifted Index, K-Index, and Total Totals are derived from all soundings. Results indicate that AIRS underestimates instability due to a dry bias at the surface and roughly 900 hPa. A simple method is presented for reconstructing a RAOB-like inversion (in terms of magnitude and altitude) within AIRS soundings, hence developing more representative RAOB-like soundings that can benefit the operational forecaster.

  19. 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

  20. Chemical and Trajectory Analysis of an Air Mass Plume from Asia

    NASA Astrophysics Data System (ADS)

    Guo, J. J.; Marrero, J. E.; Blake, D. R.

    2014-12-01

    Tracking the source of pollution events is important in understanding the transport of pollution plumes and impact on areas far from the source. Previous studies have shown that the rising contribution of Asian air pollution to the US has increased the number of days that pollution events exceed National Ambient Air Quality Standards (NAAQS). Whole air samples collected over the Edwards Air Force Base during a June 2014 NASA Student Airborne Research Program (SARP) flight exhibited enhancements in the concentrations of several compounds between 23-32 thousand feet. Chemical tracer analysis of these high altitude samples reveal that the air does not correspond to California emitted air. Chemical signatures in the plume, including high levels of OCS, chloroform, and methyl chloride, and low levels of methyl bromide, indicate that the plume was most heavily influence by coal combustion with contributions from biomass burning events from Asia. Low concentrations of ethene at the high altitude despite enhanced concentrations of ethane and ethyne suggest that this plume was aged. Further analysis of the plume using meteorological wind trajectories reveal that the plume had originated in China approximately 4-5 days prior. This is faster than results from previous studies that had found a Spring transport time of approximately 6 days.

  1. A signal transduction score flow algorithm for cyclic cellular pathway analysis, which combines transcriptome and ChIP-seq data.

    PubMed

    Isik, Zerrin; Ersahin, Tulin; Atalay, Volkan; Aykanat, Cevdet; Cetin-Atalay, Rengul

    2012-10-30

    Determination of cell signalling behaviour is crucial for understanding the physiological response to a specific stimulus or drug treatment. Current approaches for large-scale data analysis do not effectively incorporate critical topological information provided by the signalling network. We herein describe a novel model- and data-driven hybrid approach, or signal transduction score flow algorithm, which allows quantitative visualization of cyclic cell signalling pathways that lead to ultimate cell responses such as survival, migration or death. This score flow algorithm translates signalling pathways as a directed graph and maps experimental data, including negative and positive feedbacks, onto gene nodes as scores, which then computationally traverse the signalling pathway until a pre-defined biological target response is attained. Initially, experimental data-driven enrichment scores of the genes were computed in a pathway, then a heuristic approach was applied using the gene score partition as a solution for protein node stoichiometry during dynamic scoring of the pathway of interest. Incorporation of a score partition during the signal flow and cyclic feedback loops in the signalling pathway significantly improves the usefulness of this model, as compared to other approaches. Evaluation of the score flow algorithm using both transcriptome and ChIP-seq data-generated signalling pathways showed good correlation with expected cellular behaviour on both KEGG and manually generated pathways. Implementation of the algorithm as a Cytoscape plug-in allows interactive visualization and analysis of KEGG pathways as well as user-generated and curated Cytoscape pathways. Moreover, the algorithm accurately predicts gene-level and global impacts of single or multiple in silico gene knockouts. PMID:23042589

  2. Transcriptome-Based Analysis of Molecular Pathways for Clusterin Functions in Kidney Cells.

    PubMed

    Dairi, Ghida; Guan, Qiunong; Roshan-Moniri, Mani; Collins, Colin C; Ong, Christopher J; Gleave, Martin E; Nguan, Christopher Y C; Du, Caigan

    2016-12-01

    Clusterin (CLU) is a chaperone-like protein and plays a protective role against renal ischemia-reperfusion injury (IRI); however, the molecular pathways for its functions in the kidney are not fully understood. This study was designed to investigate CLU-mediating pathways in kidney cells by using bioinformatics analysis. CLU null renal tubular epithelial cells (TECs) expressing human CLU cDNA (TEC-CLU(hCLU) ) or empty vector (TEC-CLU(-/-) ) were exposed to normoxia or hypoxia (1% O2 ). Transcriptome profiling with a significant twofold change was performed using SurePrint G3 Mouse Gene Expression 8 × 60 K microarray, and the signaling pathways was ranked by using Ingenuity pathway analysis. Here, we showed that compared to CLU null controls, ectopic expression of human CLU in CLU null kidney cells promoted cell growth but inhibited migration in normoxia, and enhanced cell survival in hypoxia. CLU expression affected expression of 3864 transcripts (1893 up-regulated) in normoxia and 3670 transcripts (1925 up-regulated) in hypoxia. CLU functions in normoxia were associated mostly with AKT2/PPP2R2B-dependent PI3K/AKT, PTEN, VEGF, and ERK/MAPK signaling and as well with GSK3B-mediated cell cycle progression. In addition to unfolded protein response (UPR) and/or endoplasmic reticulum (ER) stress, CLU-enhanced cell survival in hypoxia was also associated with PIK3CD/MAPK1-dependent PI3K/AKT, HIF-α, PTEN, VEGF, and ERK/MAPK signaling. In conclusion, our data showed that CLU functions in kidney cells were mainly mediated in a cascade manner by PI3K/AKT, PTEN, VEGF, and ERK/MAPK signaling, and specifically by activation of UPR/ER stress in hypoxia, providing new insights into the protective role of CLU in the kidney. J. Cell. Physiol. 231: 2628-2638, 2016. © 2016 Wiley Periodicals, Inc. PMID:27155085

  3. Comprehensive Analysis of the Triterpenoid Saponins Biosynthetic Pathway in Anemone flaccida by Transcriptome and Proteome Profiling

    PubMed Central

    Zhan, Chuansong; Li, Xiaohua; Zhao, Zeying; Yang, Tewu; Wang, Xuekui; Luo, Biaobiao; Zhang, Qiyun; Hu, Yanru; Hu, Xuebo

    2016-01-01

    Background: Anemone flaccida Fr. Shmidt (Ranunculaceae), commonly known as ‘Di Wu’ in China, is a perennial herb with limited distribution. The rhizome of A. flaccida has long been used to treat arthritis as a tradition in China. Studies disclosed that the plant contains a rich source of triterpenoid saponins. However, little is known about triterpenoid saponins biosynthesis in A. flaccida. Results: In this study, we conducted the tandem transcriptome and proteome profiling of a non-model medicinal plant, A. flaccida. Using Illumina HiSeq 2000 sequencing and iTRAQ technique, a total of 46,962 high-quality unigenes were obtained with an average sequence length of 1,310 bp, along with 1473 unique proteins from A. flaccida. Among the A. flaccida transcripts, 36,617 (77.97%) showed significant similarity (E-value < 1e-5) to the known proteins in the public database. Of the total 46,962 unigenes, 36,617 open reading frame (ORFs) were predicted. By the fragments per kilobases per million reads (FPKM) statistics, 14,004 isoforms/unigenes were found to be upregulated, and 14,090 isoforms/unigenes were down-regulated in the rhizomes as compared to those in the leaves. Based on the bioinformatics analysis, all possible enzymes involved in the triterpenoid saponins biosynthetic pathway of A. flaccida were identified, including cytosolic mevalonate pathway (MVA) and the plastidial methylerythritol pathway (MEP). Additionally, a total of 126 putative cytochrome P450 (CYP450) and 32 putative UDP glycosyltransferases were selected as the candidates of triterpenoid saponins modifiers. Among them, four of them were annotated as the gene of CYP716A subfamily, the key enzyme in the oleanane-type triterpenoid saponins biosynthetic pathway. Furthermore, based on RNA-Seq and proteome analysis, as well as quantitative RT-PCR verification, the expression level of gene and protein committed to triterpenoids biosynthesis in the leaf versus the rhizome was compared. Conclusion: A

  4. Label-free quantitative phosphoproteomic analysis reveals differentially regulated proteins and pathway in PRRSV-infected pulmonary alveolar macrophages.

    PubMed

    Luo, Rui; Fang, Liurong; Jin, Hui; Wang, Dang; An, Kang; Xu, Ningzhi; Chen, Huanchun; Xiao, Shaobo

    2014-03-01

    Porcine reproductive and respiratory syndrome virus (PRRSV) is an important pathogen of swine worldwide and causes significant economic losses. Through regulating the host proteins phosphorylation, PRRSV was found to manipulate the activities of several signaling molecules to regulate innate immune responses. However, the role of protein phosphorylation during PRRSV infection and the signal pathways responsible for it are relatively unknown. Here liquid chromatography-tandem mass spectrometry for label-free quantitative phosphoproteomics was applied to systematically investigate the global phosphorylation events in PRRSV-infected pulmonary alveolar macrophages. In total, we identified 2125 unique phosphosites, of which the phosphorylation level of 292 phosphosites on 242 proteins and 373 phosphosites on 249 proteins was significantly altered at 12 and 36 h pi, respectively. The phosphoproteomics data were analyzed using ingenuity pathways analysis to identify defined canonical pathways and functional networks. Pathway analysis revealed that PRRSV-induced inflammatory cytokines production was probably due to the activation of mitogen-activated protein kinase and NF-κB signal pathway, which were regulated by several protein kinases during virus infection. Interacting network analysis indicated that altered phosphoproteins were involved in cellular assembly and organization, protein synthesis, molecular transport, and signal transduction in PRRSV infected cells. These pathways and functional networks analysis could provide direct insights into the biological significance of phosphorylation events modulated by PRRSV and may help us elucidate the pathogenic mechanisms of PRRSV infection. PMID:24533505

  5. Numerical analysis of air-flow and temperature field in a passenger car compartment

    NASA Astrophysics Data System (ADS)

    Kamar, Haslinda Mohamed; Kamsah, Nazri; Mohammad Nor, Ahmad Miski

    2012-06-01

    This paper presents a numerical study on the temperature field inside a passenger's compartment of a Proton Wira saloon car using computational fluid dynamics (CFD) method. The main goal is to investigate the effects of different glazing types applied onto the front and rear windscreens of the car on the distribution of air-temperature inside the passenger compartment in the steady-state conditions. The air-flow condition in the passenger's compartment is also investigated. Fluent CFD software was used to develop a three-dimensional symmetrical model of the passenger's compartment. Simplified representations of the driver and one rear passenger were incorporated into the CFD model of the passenger's compartment. Two types of glazing were considered namely clear insulated laminated tint (CIL) with a shading coefficient of 0.78 and green insulated laminate tint (GIL) with a shading coefficient of 0.5. Results of the CFD analysis were compared with those obtained when the windscreens are made up of clear glass having a shading coefficient of 0.86. Results of the CFD analysis show that for a given glazing material, the temperature of the air around the driver is slightly lower than the air around the rear passenger. Also, the use of GIL glazing material on both the front and rear windscreens significantly reduces the air temperature inside the passenger's compartment of the car. This contributes to a better thermal comfort condition to the occupants. Swirling air flow condition occurs in the passenger compartment. The air-flow intensity and velocity are higher along the side wall of the passenger's compartment compared to that along the middle section of the compartment. It was also found that the use of glazing materials on both the front and rear windscreen has no significant effects on the air-flow condition inside the passenger's compartment of the car.

  6. 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

  7. Model analysis and nonlinear control of air compressors

    NASA Astrophysics Data System (ADS)

    Sari, Gholam-Reza

    For decades, gas turbines have been important, widespread, and reliable devices in the field of power generation, petrochemical industry, and aeronautics. They employ centrifugal and axial compressors which suffer from aerodynamic instabilities, namely, surge and rotating stall. These performance limiting instabilities can cause component stress, lifespan reduction, noise, and vibration. Furthermore, in variable speed axial compressors (VSACs), speed variations affect the system stability and can lead to surge and rotating stall. This limits the rate of speed variations and results in important performance penalties. The present work firstly addresses the bifurcation analysis of VSACs' model to investigate the impact of speed dynamics on the stability of efficient operating points. Here, the rate of speed variations (acceleration rate) is defined as a new parameter of the model and a detailed numerical bifurcation analysis is provided. The results of time-domain simulations not only validate the results of bifurcation analysis, but also broaden our knowledge about the transient response of the model, which is a matter of importance as well. The analysis reveals that speed variations can lead to a fully developed rotating stall as well as the previously reported temporary stall developments. The results show that the developed instabilities depend to a great extent on the acceleration rate. The impact of other key issues such as throttle gain, viscosity factor, initial speed, final speed, and the contribution of stall modes are also explored. From the control point of view, despite reported achievements, robust control design for compression systems remains a challenging problem. In this work, at first, two nonlinear approaches are proposed to tackle the stability problem of constant-speed axial compressors (CSACs). The first approach is a robust passivity-based control and the second one is a second order sliding mode control. The approaches tackle the challenging

  8. 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

  9. 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. PMID:22704552

  10. GWAS-based pathway analysis differentiates between fluid and crystallized intelligence.

    PubMed

    Christoforou, A; Espeseth, T; Davies, G; Fernandes, C P D; Giddaluru, S; Mattheisen, M; Tenesa, A; Harris, S E; Liewald, D C; Payton, A; Ollier, W; Horan, M; Pendleton, N; Haggarty, P; Djurovic, S; Herms, S; Hoffman, P; Cichon, S; Starr, J M; Lundervold, A; Reinvang, I; Steen, V M; Deary, I J; Le Hellard, S

    2014-09-01

    Cognitive abilities vary among people. About 40-50% of this variability is due to general intelligence (g), which reflects the positive correlation among individuals' scores on diverse cognitive ability tests. g is positively correlated with many life outcomes, such as education, occupational status and health, motivating the investigation of its underlying biology. In psychometric research, a distinction is made between general fluid intelligence (gF) - the ability to reason in novel situations - and general crystallized intelligence (gC) - the ability to apply acquired knowledge. This distinction is supported by developmental and cognitive neuroscience studies. Classical epidemiological studies and recent genome-wide association studies (GWASs) have established that these cognitive traits have a large genetic component. However, no robust genetic associations have been published thus far due largely to the known polygenic nature of these traits and insufficient sample sizes. Here, using two GWAS datasets, in which the polygenicity of gF and gC traits was previously confirmed, a gene- and pathway-based approach was undertaken with the aim of characterizing and differentiating their genetic architecture. Pathway analysis, using genes selected on the basis of relaxed criteria, revealed notable differences between these two traits. gF appeared to be characterized by genes affecting the quantity and quality of neurons and therefore neuronal efficiency, whereas long-term depression (LTD) seemed to underlie gC. Thus, this study supports the gF-gC distinction at the genetic level and identifies functional annotations and pathways worthy of further investigation. PMID:24975275

  11. GWAS-based pathway analysis differentiates between fluid and crystallized intelligence

    PubMed Central

    Christoforou, A; Espeseth, T; Davies, G; Fernandes, C P D; Giddaluru, S; Mattheisen, M; Tenesa, A; Harris, S E; Liewald, D C; Payton, A; Ollier, W; Horan, M; Pendleton, N; Haggarty, P; Djurovic, S; Herms, S; Hoffman, P; Cichon, S; Starr, J M; Lundervold, A; Reinvang, I; Steen, V M; Deary, I J; Le Hellard, S

    2014-01-01

    Cognitive abilities vary among people. About 40–50% of this variability is due to general intelligence (g), which reflects the positive correlation among individuals' scores on diverse cognitive ability tests. g is positively correlated with many life outcomes, such as education, occupational status and health, motivating the investigation of its underlying biology. In psychometric research, a distinction is made between general fluid intelligence (gF) – the ability to reason in novel situations – and general crystallized intelligence (gC) – the ability to apply acquired knowledge. This distinction is supported by developmental and cognitive neuroscience studies. Classical epidemiological studies and recent genome-wide association studies (GWASs) have established that these cognitive traits have a large genetic component. However, no robust genetic associations have been published thus far due largely to the known polygenic nature of these traits and insufficient sample sizes. Here, using two GWAS datasets, in which the polygenicity of gF and gC traits was previously confirmed, a gene- and pathway-based approach was undertaken with the aim of characterizing and differentiating their genetic architecture. Pathway analysis, using genes selected on the basis of relaxed criteria, revealed notable differences between these two traits. gF appeared to be characterized by genes affecting the quantity and quality of neurons and therefore neuronal efficiency, whereas long-term depression (LTD) seemed to underlie gC. Thus, this study supports the gF–gC distinction at the genetic level and identifies functional annotations and pathways worthy of further investigation. PMID:24975275

  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 Analysis of Adaptive Responses to MAP Kinase Pathway Blockade in BRAF Mutant Melanoma.

    PubMed

    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

  14. 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

  15. 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

  16. In silico pathway analysis in cervical carcinoma reveals potential new targets for treatment.

    PubMed

    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

    2016-01-19

    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

  17. Parametric time-series analysis of daily air pollutants of city of Shumen, Bulgaria

    NASA Astrophysics Data System (ADS)

    Ivanov, A.; Voynikova, D.; Gocheva-Ilieva, S.; Boyadzhiev, D.

    2012-10-01

    The urban air pollution is one of the main factors determining the ambient air quality, which affects on the human health and the environment. In this paper parametric time series models are obtained for studying the distribution over time of primary pollutants as sulphur and nitrogen oxides, particulate matter and a secondary pollutant ground level ozon in the town of Shumen, Bulgaria. The methods of factor analysis and ARIMA are used to carry out the time series analysis based on hourly average data in 2011 and first quarter of 2012. The constructed models are applied for a short-term air pollution forecasting. The results are estimated on the basis of national and European regulation indices. The sources of pollutants in the region and their harmful effects on human health are also discussed.

  18. Screening and functional pathway analysis of genes associated with pediatric allergic asthma using a DNA microarray

    PubMed Central

    LU, LI-QUN; LIAO, WEI

    2015-01-01

    The present study aimed to identify differentially expressed genes (DEGs) associated with pediatric allergic asthma, and to analyze the functional pathways of the selected target genes, in order to explore the pathogenesis of the disease. The GSE18965 gene expression profile was downloaded from the Gene Expression Omnibus database and was preprocessed. This gene expression profile consisted of seven normal samples and nine samples from patients with pediatric allergic asthma. The DEGs between the normal and pediatric allergic asthma samples were screened using limma package in R, and the cut-off value was set at false discovery rate <0.05 and log fold change >1. Following hierarchical clustering of the DEGs based on the expression profiles, the up- and downregulated genes underwent a functional enrichment analysis by topological approach (P<0.05), using the Database for Annotation, Visualization and Integrated Discovery. A total of 127 DEGs were identified between the normal and pediatric allergic asthma samples. The up- and downregulated genes were significantly enriched in the actin filament-based process and the monosaccharide metabolic process, respectively. Seven downregulated DEGs (M6PR, TPP1, GLB1, NEU1, ACP2, LAMP1 and HGSNAT) were identified in the lysosomal pathway, with P=6.4×10−9. These results suggested that variation in lysosomal function, triggered by the seven downregulated genes, may lead to aberrant functioning of the T lymphocytes, resulting in asthma. Further research regarding the treatment of pediatric allergic asthma through targeting lysosomal function is required. PMID:25633562

  19. Gene-Based Mapping and Pathway Analysis of Metabolic Traits in Dairy Cows

    PubMed Central

    Ha, Ngoc-Thuy; Gross, Josef Johann; van Dorland, Annette; Tetens, Jens; Thaller, Georg; Schlather, Martin; Bruckmaier, Rupert; Simianer, Henner

    2015-01-01

    The metabolic adaptation of dairy cows during the transition period has been studied intensively in the last decades. However, until now, only few studies have paid attention to the genetic aspects of this process. Here, we present the results of a gene-based mapping and pathway analysis with the measurements of three key metabolites, (1) non-esterified fatty acids (NEFA), (2) beta-hydroxybutyrate (BHBA) and (3) glucose, characterizing the metabolic adaptability of dairy cows before and after calving. In contrast to the conventional single-marker approach, we identify 99 significant and biologically sensible genes associated with at least one of the considered phenotypes and thus giving evidence for a genetic basis of the metabolic adaptability. Moreover, our results strongly suggest three pathways involved in the metabolism of steroids and lipids are potential candidates for the adaptive regulation of dairy cows in their early lactation. From our perspective, a closer investigation of our findings will lead to a step forward in understanding the variability in the metabolic adaptability of dairy cows in their early lactation. PMID:25789767

  20. Structural analysis of mevalonate-3-kinase provides insight into the mechanisms of isoprenoid pathway decarboxylases

    PubMed Central

    Vinokur, Jeffrey M; Korman, Tyler P; Sawaya, Michael R; Collazo, Michael; Cascio, Duillio; Bowie, James U

    2015-01-01

    In animals, cholesterol is made from 5-carbon building blocks produced by the mevalonate pathway. Drugs that inhibit the mevalonate pathway such as atorvastatin (lipitor) have led to successful treatments for high cholesterol in humans. Another potential target for the inhibition of cholesterol synthesis is mevalonate diphosphate decarboxylase (MDD), which catalyzes the phosphorylation of (R)-mevalonate diphosphate, followed by decarboxylation to yield isopentenyl pyrophosphate. We recently discovered an MDD homolog, mevalonate-3-kinase (M3K) from Thermoplasma acidophilum, which catalyzes the identical phosphorylation of (R)-mevalonate, but without concomitant decarboxylation. Thus, M3K catalyzes half the reaction of the decarboxylase, allowing us to separate features of the active site that are required for decarboxylation from features required for phosphorylation. Here we determine the crystal structure of M3K in the apo form, and with bound substrates, and compare it to MDD structures. Structural and mutagenic analysis reveals modifications that allow M3K to bind mevalonate rather than mevalonate diphosphate. Comparison to homologous MDD structures show that both enzymes employ analogous Arg or Lys residues to catalyze phosphate transfer. However, an invariant active site Asp/Lys pair of MDD previously thought to play a role in phosphorylation is missing in M3K with no functional replacement. Thus, we suggest that the invariant Asp/Lys pair in MDD may be critical for decarboxylation rather than phosphorylation. PMID:25422158

  1. 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

  2. Nanosystem self-assembly pathways discovered via all-atom multiscale analysis.

    PubMed

    Pankavich, Stephen D; Ortoleva, Peter J

    2012-07-26

    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 time scale 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

  3. Aging Chart: a community resource for rapid exploratory pathway analysis of age-related processes.

    PubMed

    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

  4. 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).

  5. Analysis of breathing air flow patterns in thermal imaging.

    PubMed

    Fei, Jin; Pavlidis, Ioannis

    2006-01-01

    We introduce a novel methodology to characterize breathing patterns based on thermal infrared imaging. We have retrofitted a Mid-Wave Infra-Red (MWIR) imaging system with a narrow band-pass filter in the CO(2) absorption band (4130 - 4427 nm). We use this system to record the radiation information from within the breathing flow region. Based on this information we compute the mean dynamic thermal signal of breath. The breath signal is quasi-periodic due to the interleaving of high and low intensities corresponding to expirations and inspirations respectively. We sample the signal at a constant rate and then filter the high frequency noise due to tracking instability. We detect the breathing cycles through zero cross thresholding, which is insensitive to noise around the zero line. We normalize the breathing cycles and align them at the transition point from inhalation to exhalation. Then, we compute the mean breathing cycle. We use the first eight (8) harmonic components of the mean cycle to characterize the breathing pattern. The harmonic analysis highlights the intra-individual similarity of breathing patterns. Our method opens the way for desktop, unobtrusive monitoring of human respiration and may find widespread applications in clinical studies of chronic ailments. It also brings up the intriguing possibility of using breathing patterns as a novel biometric. PMID:17945610

  6. A Genetic Mosaic Analysis With a Repressible Cell Marker Screen to Identify Genes Involved in Tracheal Cell Migration During Drosophila Air Sac Morphogenesis

    PubMed Central

    Chanut-Delalande, Hélène; Jung, Alain C.; Lin, Li; Baer, Magdalena M.; Bilstein, Andreas; Cabernard, Clemens; Leptin, Maria; Affolter, Markus

    2007-01-01

    Branching morphogenesis of the Drosophila tracheal system relies on the fibroblast growth factor receptor (FGFR) signaling pathway. The Drosophila FGF ligand Branchless (Bnl) and the FGFR Breathless (Btl/FGFR) are required for cell migration during the establishment of the interconnected network of tracheal tubes. However, due to an important maternal contribution of members of the FGFR pathway in the oocyte, a thorough genetic dissection of the role of components of the FGFR signaling cascade in tracheal cell migration is impossible in the embryo. To bypass this shortcoming, we studied tracheal cell migration in the dorsal air sac primordium, a structure that forms during late larval development. Using a mosaic analysis with a repressible cell marker (MARCM) clone approach in mosaic animals, combined with an ethyl methanesulfonate (EMS)-mutagenesis screen of the left arm of the second chromosome, we identified novel genes implicated in cell migration. We screened 1123 mutagenized lines and identified 47 lines displaying tracheal cell migration defects in the air sac primordium. Using complementation analyses based on lethality, mutations in 20 of these lines were genetically mapped to specific genomic areas. Three of the mutants were mapped to either the Mhc or the stam complementation groups. Further experiments confirmed that these genes are required for cell migration in the tracheal air sac primordium. PMID:17603108

  7. 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.

  8. Recent theoretical advances in analysis of AIRS/AMSU sounding data

    NASA Astrophysics Data System (ADS)

    Susskind, Joel

    2007-04-01

    The AIRS Science Team Version 5.0 retrieval algorithm will become operational at the Goddard DAAC in early 2007 in the near real-time analysis of AIRS/AMSU sounding data. This algorithm contains many significant theoretical advances over the AIRS Science Team Version 4.0 retrieval algorithm used previously. Three very significant developments are: 1) the development and implementation of a very accurate Radiative Transfer Algorithm (RTA) which allows for accurate treatment of non-Local Thermodynamic Equilibrium (non-LTE) effects on shortwave sounding channels; 2) the development of methodology to obtain very accurate case by case product error estimates which are in turn used for quality control; and 3) development of an accurate AIRS only cloud clearing and retrieval system. These theoretical improvements taken together enabled a new methodology to be developed which further improves soundings in partially cloudy conditions, without the need for microwave observations in the cloud clearing step as has been done previously. In this methodology, longwave CO II channel observations in the spectral region 700 cm -1 to 750 cm -1 are used exclusively for cloud clearing purposes, while shortwave CO II channels in the spectral region 2195 cm -1 to 2395 cm -1 are used for temperature sounding purposes. The new methodology is described briefly and results are shown, including comparison with those using AIRS Version 4, as well as a forecast impact experiment assimilating AIRS Version 5.0 retrieval products in the Goddard GEOS 5 Data Assimilation System.

  9. 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

  10. 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. PMID:22143760

  11. Acoustic analysis of primate air sacs and their effect on vocalization.

    PubMed

    de Boer, Bart

    2009-12-01

    This paper presents an analysis of the acoustic impedance of primate air sacs and their interaction with the vocal tract. A lumped element model is derived and it is found that the inertance of the neck and the volume of the air sac are relevant, as well as the mass and stiffness of the walls (depending on the tissue). It is also shown that at low frequencies, radiation from the air sac can be non-negligible, even if the mouth is open. It is furthermore shown that an air sac can add one or two low resonances to the resonances of the oral tract, and that it shifts up the oral tract's resonances below approximately 2000 Hz, and shifts them closer together. The theory was verified by acoustic measurements and applied to the red howler monkey (Alouatta seniculus) and the siamang (Symphalangus syndactylus). The theory describes the physical models and the siamang calls correctly, but appears incomplete for the howler monkey vocalizations. The relation between air sacs and the evolution of speech is discussed briefly, and it is proposed that an air sac would reduce the ability to produce distinctive speech, but would enhance the impression of size of the vocalizer. PMID:20000947

  12. 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

  13. 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. PMID:26872625

  14. 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…

  15. 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...

  16. 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...

  17. 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...

  18. AIR LAND WATER ANALYSIS SYSTEM (ALEAS): A MULTI-MEDIA MODEL FOR TOXIC SUBSTANCES

    EPA Science Inventory

    The Air Land Water Analysis System (ALWAS) is a multi-media environmental model for describing the atmospheric dispersion of toxicants, the surface runoff of deposited toxicants, and the subsequent fate of these materials in surface water bodies. ALWAS dipicts the spatial and tem...

  19. 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.

  20. Analysis of vector wind change with respect to time for Vandenberg Air Force Base, California

    NASA Technical Reports Server (NTRS)

    Adelfang, S. I.

    1978-01-01

    A statistical analysis of the temporal variability of wind vectors at 1 km altitude intervals from 0 to 27 km altitude taken from a 10-year data sample of twice-daily rawinsode wind measurements over Vandenberg Air Force Base, California is presented.

  1. ANALYSIS SYSTEM FOR TOTAL SULFURIC ACID IN AMBIENT AIR. DEVELOPMENT AND PRELIMINARY EVALUATION

    EPA Science Inventory

    A total sulfuric acid analysis (TSAA) system was developed and shown to provide quantitative determinations of sulfuric acid in air at concentrations as low as 0.26 micrograms/cu m. Quantitation at lower concentrations appears to be possible. The general approach in the design an...

  2. 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...

  3. 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.

  4. AN ANALYSIS OF AIR POLLUTION AND ITS HEALTH EFFECTS: WASHINGTON, DC. METROPOLITAN AREA

    EPA Science Inventory

    The study represents an extension of research begun under a contract (No. 68-01-3144) funded jointly by the U.S. Environmental Protection Agency and the U.S. Department of Transportation entitled, 'Air Pollution and Health in Washington, D.C.: An Analysis of Some Acute Health Eff...

  5. A METHOD FOR THE SAMPLING AND ANALYSIS OF POLYCHLORINATED BIPHENYLS (PCBS) IN AMBIENT AIR

    EPA Science Inventory

    A method was developed for the sampling and analysis of polychlorinated biphenyls (PCBs) in air. An easily constructed, high-volume sampling system is employed with porous polyurethane foam as the collection medium. The sample is collected at the rate of 0.6 to 1.0 cu m per minut...

  6. AN OBJECTIVE ANALYSIS TECHNIQUE FOR THE REGIONAL AIR POLLUTION STUDY. PART I

    EPA Science Inventory

    This report documents the development of an objective analysis program for the mesoscale gridding of wind and temperature for the Regional Air Pollution Study being conducted in St. Louis by the Environmental Protection Agency. The program is designed to produce a 5-km spaced hor...

  7. AN OBJECTIVE ANALYSIS TECHNIQUE FOR THE REGIONAL AIR POLLUTION STUDY. PART II

    EPA Science Inventory

    This report discusses the application of objective analysis techniques to the computation of trajectories from surface wind observations of the Regional Air Pollution Study in St. Louis. Trajectories were computed over a 100-kilometer square grid centered on St. Louis for two 5-h...

  8. Detection of Expressional Changes Induced by Intrauterine Growth Restriction in the Developing Rat Mammary Gland via Exploratory Pathways Analysis

    PubMed Central

    Beinder, Lea; Faehrmann, Nina; Wachtveitl, Rainer; Winterfeld, Ilona; Hartner, Andrea; Menendez-Castro, Carlos; Rauh, Manfred; Ruebner, Matthias; Huebner, Hanna; Noegel, Stephanie C.; Doerr, Helmuth G.; Rascher, Wolfgang; Fahlbusch, Fabian B.

    2014-01-01

    Background Intrauterine growth restriction (IUGR) is thought to lead to fetal programming that in turn contributes to developmental changes of many organs postnatally. There is evidence that IUGR is a risk factor for the development of metabolic and cardiovascular disease later in life. A higher incidence of breast cancer was also observed after IUGR. This could be due to changes in mammary gland developmental pathways. We sought to characterise IUGR-induced alterations of the complex pathways of mammary development at the level of the transcriptome in a rat model of IUGR, using pathways analysis bioinformatics. Methodology/Principal Findings We analysed the mammary glands of Wistar rats with IUGR induced by maternal low protein (LP) diet at the beginning (d21) and the end (d28) of pubertal ductal morphogenesis. Mammary glands of the LP group were smaller in size at d28, however did not show morphologic changes. We identified multiple differentially expressed genes in the mammary gland using Agilent SurePrint arrays at d21 and d28. In silico analysis was carried out using Ingenuity Pathways Analysis. In mammary gland tissue of LP rats at d21 of life a prominent upregulation of WT1 and CDKN1A (p21) expression was observed. Differentially regulated genes were associated with the extracellular regulated kinase (ERK)-1/-2 pathway. Western Blot analysis showed reduced levels of phosphorylated ERK-1/-2 in the mammary glands of the LP group at d21. To identify possible changes in circulating steroid levels, serum LC-Tandem mass-spectrometry was performed. LP rats showed higher serum progesterone levels and an increased corticosterone/dehydrocorticosterone-ratio at d28. Conclusions/Significance Our data obtained from gene array analysis support the hypothesis that IUGR influences pubertal development of the rat mammary gland. We identified prominent differential regulation of genes and pathways for factors regulating cell cycle and growth. Moreover, we detected new

  9. Determination of background concentrations for air quality models using spectral analysis and filtering of monitoring data

    NASA Astrophysics Data System (ADS)

    Tchepel, O.; Costa, A. M.; Martins, H.; Ferreira, J.; Monteiro, A.; Miranda, A. I.; Borrego, C.

    2010-01-01

    The use of background concentrations in air pollution modelling is usually a critical issue and a source of errors. The current work proposes an approach for the estimation of background concentrations using air quality measured data decomposed on baseline and short-term components. For this purpose, the spectral density was obtained for air quality monitoring data based on the Fourier series analysis. After, short-term fluctuations associated with the influence of local emissions and dispersion conditions were extracted from the original measurements using an iterative moving-average filter and taking into account the contribution of higher frequencies determined from the spectral analysis. The deterministic component obtained by the filtering is characterised by wider spatial and temporal representativeness than original monitoring data and is assumed to be appropriate for establishing the background values. This methodology was applied to define background concentrations of particulate matter (PM 10) used as input data for a local scale CFD model, and compared with an alternative approach using background concentrations provided by a mesoscale air quality modelling system. The study is focused on a selected domain within the Lisbon urban area (Portugal). The results present a better performance for the microscale model when initialised by decomposed time series and demonstrate the importance of the proposed methodology in reducing the uncertainty of the model predictions. The decomposition of air quality measurements and the removal of short-term fluctuations discussed in the work is a valuable technique to determine representative background concentrations.

  10. 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.

  11. Meta-analysis of gene expression profiles indicates genes in spliceosome pathway are up-regulated in hepatocellular carcinoma (HCC).

    PubMed

    Xu, Weijin; Huang, Huixing; Yu, Long; Cao, Lihuan

    2015-04-01

    Hepatocellular carcinoma (HCC) is among the commonest kind of malignant tumors, which accounts for more than 500,000 cases of newly diagnosed cancer annually. Many microarray studies for identifying differentially expressed genes (DEGs) in HCC have been conducted, but results have varied across different studies. Here, we performed a meta-analysis of publicly available microarray Gene Expression Omnibus datasets, which covers five independent studies, containing 753 HCC samples and 638 non-tumor liver samples. We identified 192 DEGs that were consistently up-regulated in HCC vs. normal liver tissue. For the 192 up-regulated genes, we performed Kyoto Encyclopedia of Genes and Genomes pathway analysis. To our surprise, besides several cell growth-related pathways, spliceosome pathway was also up-regulated in HCC. For further exploring the relationship between spliceosome pathway and HCC, we investigated the expression data of spliceosome pathway genes in 15 independent studies in Nextbio database ( https://www.nextbio.com/b/nextbioCorp.nb ). It was found that many genes of spliceosome pathway such as HSPA1A, SNRPE, SF3B2, SF3B4 and TRA2A genes which we identified to be up-regulated in our meta-analysis were generally overexpressed in HCC. At last, using real-time PCR, we also found that BUD31, SF3B2, SF3B4, SNRPE, SPINK1, TPA2A and HSPA1A genes are significantly up-regulated in clinical HCC samples when compared to the corresponding non-tumorous liver tissues. Our study for the first time indicates that many genes of spliceosome pathway are up-regulated in HCC. This finding might put new insights for people's understanding about the relationship of spliceosome pathway and HCC. PMID:25731616

  12. Proteomic Analysis of Human Brown Adipose Tissue Reveals Utilization of Coupled and Uncoupled Energy Expenditure Pathways.

    PubMed

    Müller, Sebastian; Balaz, Miroslav; Stefanicka, Patrik; Varga, Lukas; Amri, Ez-Zoubir; Ukropec, Jozef; Wollscheid, Bernd; Wolfrum, Christian

    2016-01-01

    Human brown adipose tissue (BAT) has become an attractive target to combat the current epidemical spread of obesity and its associated co-morbidities. Currently, information on its functional role is primarily derived from rodent studies. Here, we present the first comparative proteotype analysis of primary human brown adipose tissue versus adjacent white adipose tissue, which reveals significant quantitative differences in protein abundances and in turn differential functional capabilities. The majority of the 318 proteins with increased abundance in BAT are associated with mitochondrial metabolism and confirm the increased oxidative capacity. In addition to uncoupling protein 1 (UCP1), the main functional effector for uncoupled respiration, we also detected the mitochondrial creatine kinases (CKMT1A/B, CKMT2), as effective modulators of ATP synthase coupled respiration, to be exclusively expressed in BAT. The abundant expression and utilization of both energy expenditure pathways in parallel highlights the complex functional involvement of BAT in human physiology. PMID:27418403

  13. On an Additive Semigraphoid Model for Statistical Networks With Application to Pathway Analysis

    PubMed Central

    Li, Bing; Chun, Hyonho; Zhao, Hongyu

    2014-01-01

    We introduce a nonparametric method for estimating non-gaussian graphical models based on a new statistical relation called additive conditional independence, which is a three-way relation among random vectors that resembles the logical structure of conditional independence. Additive conditional independence allows us to use one-dimensional kernel regardless of the dimension of the graph, which not only avoids the curse of dimensionality but also simplifies computation. It also gives rise to a parallel structure to the gaussian graphical model that replaces the precision matrix by an additive precision operator. The estimators derived from additive conditional independence cover the recently introduced nonparanormal graphical model as a special case, but outperform it when the gaussian copula assumption is violated. We compare the new method with existing ones by simulations and in genetic pathway analysis. PMID:26401064

  14. Proteomic Analysis of Human Brown Adipose Tissue Reveals Utilization of Coupled and Uncoupled Energy Expenditure Pathways

    PubMed Central

    Müller, Sebastian; Balaz, Miroslav; Stefanicka, Patrik; Varga, Lukas; Amri, Ez-Zoubir; Ukropec, Jozef; Wollscheid, Bernd; Wolfrum, Christian

    2016-01-01

    Human brown adipose tissue (BAT) has become an attractive target to combat the current epidemical spread of obesity and its associated co-morbidities. Currently, information on its functional role is primarily derived from rodent studies. Here, we present the first comparative proteotype analysis of primary human brown adipose tissue versus adjacent white adipose tissue, which reveals significant quantitative differences in protein abundances and in turn differential functional capabilities. The majority of the 318 proteins with increased abundance in BAT are associated with mitochondrial metabolism and confirm the increased oxidative capacity. In addition to uncoupling protein 1 (UCP1), the main functional effector for uncoupled respiration, we also detected the mitochondrial creatine kinases (CKMT1A/B, CKMT2), as effective modulators of ATP synthase coupled respiration, to be exclusively expressed in BAT. The abundant expression and utilization of both energy expenditure pathways in parallel highlights the complex functional involvement of BAT in human physiology. PMID:27418403

  15. 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.

  16. Transcriptional analysis of antiviral small molecule therapeutics as agonists of the RLR pathway

    PubMed Central

    Green, R.R.; Wilkins, C.; Pattabhi, S.; Dong, R.; Loo, Y.; Gale, M.

    2016-01-01

    The recognition of pathogen associated molecular patterns (PAMPs) by pattern recognition receptors (PRR) during viral infection initiates the induction of antiviral signaling pathways, including activation of the Interferon Regulator Factor 3 (IRF3). We identified small molecule compounds that activate IRF3 through MAVS, thereby inhibiting infection by viruses of the families Flaviviridae (West Nile virus, dengue virus and hepatitis C virus), Filoviridae (Ebola virus), Orthomyxoviridae (influenza A virus), Arenaviridae (Lassa virus) and Paramyxoviridae (respiratory syncytial virus, Nipah virus) (1). In this study, we tested a lead compound along with medicinal chemistry-derived analogs to compare the gene transcriptional profiles induced by these molecules to that of other known MAVS-dependent IRF3 agonists. Transcriptional analysis of these small molecules revealed the induction of specific antiviral genes and identified a novel module of host driven immune regulated genes that suppress infection of a range of RNA viruses. Microarray data can be found in Gene Expression Omnibus (GSE74047). PMID:26981429

  17. 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.

  18. Comprehensive profiling analysis of actively resorbing osteoclasts identifies critical signaling pathways regulated by bone substrate

    PubMed Central

    Purdue, P. Edward; Crotti, Tania N.; Shen, Zhenxin; Swantek, Jennifer; Li, Jun; Hill, Jonathan; Hanidu, Adedayo; Dimock, Janice; Nabozny, Gerald; Goldring, Steven R.; McHugh, Kevin P.

    2014-01-01

    As the only cells capable of efficiently resorbing bone, osteoclasts are central mediators of both normal bone remodeling and pathologies associates with excessive bone resorption. However, despite the clear evidence of interplay between osteoclasts and the bone surface in vivo, the role of the bone substrate in regulating osteoclast differentiation and activation at a molecular level has not been fully defined. Here, we present the first comprehensive expression profiles of osteoclasts differentiated on authentic resorbable bone substrates. This analysis has identified numerous critical pathways coordinately regulated by osteoclastogenic cytokines and bone substrate, including the transition from proliferation to differentiation, and sphingosine-1-phosphate signaling. Whilst, as expected, much of this program is dependent upon integrin beta 3, the pre-eminent mediator of osteoclast-bone interaction, a surprisingly significant portion of the bone substrate regulated expression signature is independent of this receptor. Together, these findings identify an important hitherto underappreciated role for bone substrate in osteoclastogenesis. PMID:25534583

  19. Transcriptional analysis of antiviral small molecule therapeutics as agonists of the RLR pathway.

    PubMed

    Green, R R; Wilkins, C; Pattabhi, S; Dong, R; Loo, Y; Gale, M

    2016-03-01

    The recognition of pathogen associated molecular patterns (PAMPs) by pattern recognition receptors (PRR) during viral infection initiates the induction of antiviral signaling pathways, including activation of the Interferon Regulator Factor 3 (IRF3). We identified small molecule compounds that activate IRF3 through MAVS, thereby inhibiting infection by viruses of the families Flaviviridae (West Nile virus, dengue virus and hepatitis C virus), Filoviridae (Ebola virus), Orthomyxoviridae (influenza A virus), Arenaviridae (Lassa virus) and Paramyxoviridae (respiratory syncytial virus, Nipah virus) (1). In this study, we tested a lead compound along with medicinal chemistry-derived analogs to compare the gene transcriptional profiles induced by these molecules to that of other known MAVS-dependent IRF3 agonists. Transcriptional analysis of these small molecules revealed the induction of specific antiviral genes and identified a novel module of host driven immune regulated genes that suppress infection of a range of RNA viruses. Microarray data can be found in Gene Expression Omnibus (GSE74047). PMID:26981429

  20. KeyPathwayMiner 4.0: condition-specific pathway analysis by combining multiple omics studies and networks with Cytoscape

    PubMed Central

    2014-01-01

    Background Over the last decade network enrichment analysis has become popular in computational systems biology to elucidate aberrant network modules. Traditionally, these approaches focus on combining gene expression data with protein-protein interaction (PPI) networks. Nowadays, the so-called omics technologies allow for inclusion of many more data sets, e.g. protein phosphorylation or epigenetic modifications. This creates a need for analysis methods that can combine these various sources of data to obtain a systems-level view on aberrant biological networks. Results We present a new release of KeyPathwayMiner (version 4.0) that is not limited to analyses of single omics data sets, e.g. gene expression, but is able to directly combine several different omics data types. Version 4.0 can further integrate existing knowledge by adding a search bias towards sub-networks that contain (avoid) genes provided in a positive (negative) list. Finally the new release now also provides a set of novel visualization features and has been implemented as an app for the standard bioinformatics network analysis tool: Cytoscape. Conclusion With KeyPathwayMiner 4.0, we publish a Cytoscape app for multi-omics based sub-network extraction. It is available in Cytoscape’s app store http://apps.cytoscape.org/apps/keypathwayminer or via http://keypathwayminer.mpi-inf.mpg.de. PMID:25134827

  1. Genome-wide pathway analysis of genome-wide association studies on systemic lupus erythematosus and rheumatoid arthritis.

    PubMed

    Lee, Young Ho; Bae, Sang-Cheol; Choi, Sung Jae; Ji, Jong Dae; Song, Gwan Gyu

    2012-12-01

    The aim of this study was to explore candidate single nucleotide polymorphisms (SNPs) and candidate mechanisms of systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). Two SLE genome-wide association studies (GWASs) datasets were included in this study. Meta-analysis was conducted using 737,984 SNPs in 1,527 SLE cases and 3,421 controls of European ancestry, and 4,429 SNPs that met a threshold of p < 0.01 in a Korean RA GWAS dataset was used. ICSNPathway (identify candidate causal SNPs and pathways) analysis was applied to the meta-analysis results of the SLE GWAS datasets, and a RA GWAS dataset. The most significant result of SLE GWAS meta-analysis concerned rs2051549 in the human leukocyte antigen (HLA) region (p = 3.36E-22). In the non-HLA region, meta-analysis identified 6 SNPs associated with SLE with genome-wide significance (STAT4, TNPO3, BLK, FAM167A, and IRF5). ICSNPathway identified five candidate causal SNPs and 13 candidate causal pathways. This pathway-based analysis provides three hypotheses of the biological mechanism involved. First, rs8084 and rs7192 → HLA-DRA → bystander B cell activation. Second, rs1800629 → TNF → cytokine network. Third, rs1150752 and rs185819 → TNXB → collagen metabolic process. ICSNPathway analysis identified three candidate causal non-HLA SNPs and four candidate causal pathways involving the PADI4, MTR, PADI2, and TPH2 genes of RA. We identified five candidate SNPs and thirteen pathways, involving bystander B cell activation, cytokine network, and collagen metabolic processing, which may contribute to SLE susceptibility, and we revealed candidate causal non-HLA SNPs, genes, and pathways of RA. PMID:23053960

  2. Strigolactone pathway genes and plant architecture: association analysis and QTL detection for horticultural traits in chrysanthemum.

    PubMed

    Klie, Maik; Menz, Ina; Linde, Marcus; Debener, Thomas

    2016-04-01

    Chrysanthemums are important ornamental plants with abundant phenotypic diversity. Especially in cut-flower breeding, shoot branching is important for the success of new varieties. To assess the genetic regulation of shoot branching and other horticultural important traits, we phenotyped and genotyped two types of chrysanthemum populations: a genotype collection of 86 varieties and a biparental F1-population (MK11/3) of 160 individuals. Using two different statistical approaches, a genome-wide association analysis and a single marker ANOVA, with AFLP marker data and candidate gene markers for shoot branching, we tried to identify markers correlated to the traits of interest. As expected for the outcrossing hexasomic chrysanthemums most of the phenotypic traits showed a continuous variation in both populations. With the candidate gene approach we identified 11 significantly associated marker alleles for all 4 strigolactone pathway genes BRC1, CCD7, CCD8 and MAX2 regulating shoot branching in the genotype collection. In the MK11/3 we detected seven markers for all candidate genes except MAX2 explaining a large proportion of the variation. Using anonymous AFLP markers in the GWA with the 86 genotypes and the single locus analysis with the F1-population we could detect 15 and 17 additional marker-trait associations, respectively. Our analyses indicate a polygenic inheritance of the shoot branching in the chrysanthemum, with a fundamental role of the strigolactone pathway genes BRC1, CCD7, CCD8 and MAX2 and we identified 50 associated markers to all traits under study. These markers could be used in the selection of the parental plants for breeding chrysanthemums to enrich them for positive alleles influencing plant architecture traits. PMID:26780913

  3. Gene microarray analysis reveals a novel hypoxia signal transduction pathway in human hepatocellular carcinoma cells.

    PubMed

    Scandurro, A B; Weldon, C W; Figueroa, Y G; Alam, J; Beckman, B S

    2001-07-01

    The molecular details of hypoxia-induced cellular responses have been difficult to identify since there is as yet no known oxygen receptor. We used cDNA microarray technology to extend our studies pertaining to these molecular details in human hepatocellular carcinoma (Hep3B) cells that produce erythropoietin (Epo) in response to hypoxia. Of approximately 1200 genes in the array, those associated with integrin-linked kinase (ILK), fibronectin precursor and glycogen synthase kinase-3beta (GSK-3beta) were markedly stimulated after exposure of Hep3B cells to low oxygen (1%) for 6 h. Epo, HIF-1, and von Hippel-Lindau cDNAs were measured in parallel as markers of low oxygen responses in Hep3B cells. ILK is a serine, threonine protein kinase that interacts with the cytoplasmic domains of integrin beta1 and beta3. This interaction localizes ILK to focal adhesion plaques. ILK is stimulated by cell-fibronectin interaction as well as insulin. It is regulated in a phosphatidylinositol 3-kinase dependent manner and can phosphorylate protein kinase B (PKB/AKT) and GSK-3beta. As a result of these and other activities ILK has been shown to affect anchorage-independent cell survival, cell cycle progression and tumorigenesis in nude mice. ILK has also been implicated in the Wnt pathway and as a critical target in PTEN-dependent tumor therapies. To our knowledge this is the first report implicating the ILK pathway in low oxygen responses. Other genes identified as a result of the microarray analysis not previously known to change as a result of low oxygen treatment were elongation factor-1alpha, glycyl-tRNA synthetase, and laminin receptor protein-1. These findings were all corroborated by RT-PCR assays and in some instances Western blot analysis. PMID:11408933

  4. 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

    Jiang, Wei; Wang, Yandong; 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

  5. 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

  6. 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

  7. Energy analysis on use of air and superheated steam as drying media

    SciTech Connect

    Tarnawski, W.Z.; Mitera, J.; Borowski, P.; Klepaczka, A.

    1996-10-01

    The physical properties of air and superheated steam were analyzed in a range of temperatures applied in paper and paperboard drying processes. On the basis of tests carried out on a pilot stand the values of energy indices for air and steam drying processes are compared. With the drying media temperature as T{sub M} = 300 C, nozzle velocity {nu} = 60 m/s and using the Huang and Mujumdar model as well as relationships given by Chance a comparative analysis of the results has been carried out. Variation of several indices in the range of temperatures 100--600 C and various nozzle velocities was studied.

  8. 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.

  9. AIRE gene analysis in children with autoimmune hepatitis type I or II.

    PubMed

    Lankisch, Tim O; Mourier, Olivia; Sokal, Etienne M; Habes, Dalila; Lacaille, Florence; Bridoux-Henno, Laure; Hermeziu, Bogdan; Lenaerts, Catherine; Strassburg, Christian P; Jacquemin, Emmanuel

    2009-04-01

    The present report describes AIRE gene analysis in 25 children with autoimmune hepatitis type I or II. The heterozygous transversion c.961C > G (p.Ser278Arg) located in exon 7 was identified in 4 patients with autoimmune hepatitis type I, and mostly in those presenting with a positive family history for autoimmune diseases. In this subgroup of patients, the allelic frequency of this polymorphic variant was at least 3-fold higher than in healthy controls. These results suggest that heterozygous AIRE gene mutation may represent a genetic predisposition to childhood autoimmune hepatitis type I. PMID:19322061

  10. Donor-Specific Indirect Pathway Analysis Reveals a B-Cell-Independent Signature Which Reflects Outcomes in Kidney Transplant Recipients

    PubMed Central

    Haynes, L. D.; Jankowska-Gan, E.; Sheka, A.; Keller, M. R.; Hernandez-Fuentes, M. P.; Lechler, R. I.; Seyfert-Margolis, V.; Turka, L. A.; Newell, K. A.; Burlingham, W. J.

    2012-01-01

    To investigate the role of donor-specific indirect pathway T cells in renal transplant tolerance, we analyzed responses in peripheral blood of 45 patients using the trans-vivo delayed-type hypersensitivity assay. Subjects were enrolled into five groups—identical twin, clinically tolerant (TOL), steroid monotherapy (MONO), standard immunosuppression (SI) and chronic rejection (CR)—based on transplant type, posttransplant immunosuppression and graft function. The indirect pathway was active in all groups except twins but distinct intergroup differences were evident, corresponding to clinical status. The antidonor indirect pathway T effector response increased across patient groups (TOL < MONO < SI < CR; p < 0.0001) whereas antidonor indirect pathway T regulatory response decreased (TOL > MONO = SI > CR; p < 0.005). This pattern differed from that seen in circulating naïve B-cell numbers and in a cross-platform biomarker analysis, where patients on monotherapy were not ranked closest to TOL patients, but rather were indistinguishable from chronically rejecting patients. Cross-sectional analysis of the indirect pathway revealed a spectrum in T-regulatory:T-effector balance, ranging from TOL patients having predominantly regulatory responses to CR patients having predominantly effector responses. Therefore, the indirect pathway measurements reflect a distinct aspect of tolerance from the recently reported elevation of circulating naïve B cells, which was apparent only in recipients off immunosuppression. PMID:22151236

  11. 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.

  12. Fluctuation analysis-based risk assessment for respiratory virus activity and air pollution associated asthma incidence.

    PubMed

    Liao, Chung-Min; Hsieh, Nan-Hung; Chio, Chia-Pin

    2011-08-15

    Asthma is a growing epidemic worldwide. Exacerbations of asthma have been associated with bacterial and viral respiratory tract infections and air pollution. We correlated the asthma admission rates with fluctuations in respiratory virus activity and traffic-related air pollution, namely particulate matter with an aerodynamic diameter ≤ 10 μm (PM₁₀), nitrogen dioxide (NO₂), carbon monoxide (CO), sulfur dioxide (SO₂), and ozone (O₃). A probabilistic risk assessment framework was developed based on a detrended fluctuation analysis to predict future respiratory virus and air pollutant associated asthma incidence. Results indicated a strong association between asthma admission rate and influenza (r=0.80, p<0.05) and SO₂ level (r=0.73, p<0.05) in Taiwan in the period 2001-2008. No significant correlation was found for asthma admission and PM₁₀, O₃, NO₂, and CO. The proposed fluctuation analysis provides a simple correlation exponent describing the complex interactions of respiratory viruses and air pollutants with asthma. This study revealed that there was a 95% probability of having exceeded 2987 asthma admissions per 100,000 population. It was unlikely (30% probability) that the asthma admission rate exceeded 3492 per 100,000 population. The probability of asthma admission risk can be limited to below 50% by keeping the correlation exponent of influenza to below 0.9. We concluded that fluctuation analysis based risk assessment provides a novel predictor of asthma incidence. PMID:21663946

  13. In-air micro-PIGE measurement system for fluorine analysis of the tooth

    NASA Astrophysics Data System (ADS)

    Yasuda, K.; Hai, V. H.; Nomachi, M.; Sugaya, Y.; Yamamoto, H.

    2007-07-01

    An in-air micro-PIGE and micro-PIXE measurement system for fluorine analysis of tooth have been developed at the Wakasa Wan Energy Research Center. A proton microbeam is extracted through a thin silicon nitride window into the air and used to irradiate a tooth sample mounted on a sample stage set in air. Gamma-rays from a 19F(p, αγ) 16O reaction and characteristic X-rays are detected with a BGO detector and a Ge X-ray detector, simultaneously. The sample stage and beam scanner allow us to analyze the tooth sample over a range of 20 mm at maximum. Spot sizes of a proton beams in air at an energy of 2.5 MeV was 4 μm, in the case of a distance between the silicon nitride window and the sample of 0.2 mm and 13 μm in the case of 1.7 mm. Fluorine analysis was performed over an area of about 3 mm × 3 mm of the tooth sample. One- and two-dimensional distributions of fluorine and calcium were obtained successfully. Quantitative analysis was also performed using data for measurements of reference materials Ca 10(PO 4) 6(OH) 2-2 xF 2 x.

  14. Well-to-wheels analysis of fast pyrolysis pathways with the GREET model.

    SciTech Connect

    Han, J.; Elgowainy, A.; Palou-Rivera, I.; Dunn, J.B.; Wang, M.Q.

    2011-12-01

    The pyrolysis of biomass can help produce liquid transportation fuels with properties similar to those of petroleum gasoline and diesel fuel. Argonne National Laboratory conducted a life-cycle (i.e., well-to-wheels [WTW]) analysis of various pyrolysis pathways by expanding and employing the Greenhouse Gases, Regulated Emissions, and Energy Use in Transportation (GREET) model. The WTW energy use and greenhouse gas (GHG) emissions from the pyrolysis pathways were compared with those from the baseline petroleum gasoline and diesel pathways. Various pyrolysis pathway scenarios with a wide variety of possible hydrogen sources, liquid fuel yields, and co-product application and treatment methods were considered. At one extreme, when hydrogen is produced from natural gas and when bio-char is used for process energy needs, the pyrolysis-based liquid fuel yield is high (32% of the dry mass of biomass input). The reductions in WTW fossil energy use and GHG emissions relative to those that occur when baseline petroleum fuels are used, however, is modest, at 50% and 51%, respectively, on a per unit of fuel energy basis. At the other extreme, when hydrogen is produced internally via reforming of pyrolysis oil and when bio-char is sequestered in soil applications, the pyrolysis-based liquid fuel yield is low (15% of the dry mass of biomass input), but the reductions in WTW fossil energy use and GHG emissions are large, at 79% and 96%, respectively, relative to those that occur when baseline petroleum fuels are used. The petroleum energy use in all scenarios was restricted to biomass collection and transportation activities, which resulted in a reduction in WTW petroleum energy use of 92-95% relative to that found when baseline petroleum fuels are used. Internal hydrogen production (i.e., via reforming of pyrolysis oil) significantly reduces fossil fuel use and GHG emissions because the hydrogen from fuel gas or pyrolysis oil (renewable sources) displaces that from fossil fuel

  15. Insights into the autotrophic CO2 fixation pathway of the archaeon Ignicoccus hospitalis: comprehensive analysis of the central carbon metabolism.

    PubMed

    Jahn, Ulrike; Huber, Harald; Eisenreich, Wolfgang; Hügler, Michael; Fuchs, Georg

    2007-06-01

    Ignicoccus hospitalis is an autotrophic hyperthermophilic archaeon that serves as a host for another parasitic/symbiotic archaeon, Nanoarchaeum equitans. In this study, the biosynthetic pathways of I. hospitalis were investigated by in vitro enzymatic analyses, in vivo (13)C-labeling experiments, and genomic analyses. Our results suggest the operation of a so far unknown pathway of autotrophic CO(2) fixation that starts from acetyl-coenzyme A (CoA). The cyclic regeneration of acetyl-CoA, the primary CO(2) acceptor molecule, has not been clarified yet. In essence, acetyl-CoA is converted into pyruvate via reductive carboxylation by pyruvate-ferredoxin oxidoreductase. Pyruvate-water dikinase converts pyruvate into phosphoenolpyruvate (PEP), which is carboxylated to oxaloacetate by PEP carboxylase. An incomplete citric acid cycle is operating: citrate is synthesized from oxaloacetate and acetyl-CoA by a (re)-specific citrate synthase, whereas a 2-oxoglutarate-oxidizing enzyme is lacking. Further investigations revealed that several special biosynthetic pathways that have recently been described for various archaea are operating. Isoleucine is synthesized via the uncommon citramalate pathway and lysine via the alpha-aminoadipate pathway. Gluconeogenesis is achieved via a reverse Embden-Meyerhof pathway using a novel type of fructose 1,6-bisphosphate aldolase. Pentosephosphates are formed from hexosephosphates via the suggested ribulose-monophosphate pathway, whereby formaldehyde is released from C-1 of hexose. The organism may not contain any sugar-metabolizing pathway. This comprehensive analysis of the central carbon metabolism of I. hospitalis revealed further evidence for the unexpected and unexplored diversity of metabolic pathways within the (hyperthermophilic) archaea. PMID:17400748

  16. 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

  17. System implementation for US Air Force Global Theater Weather Analysis and Prediction System (GTWAPS)

    SciTech Connect

    Simunich, K.L.; Pinkerton, S.C.; Michalakes, J.G.; Christiansen, J.H.

    1997-03-01

    The Global Theater Weather Analysis and Prediction System (GTWAPS) is intended to provide war fighters and decision makers with timely, accurate, and tailored meteorological and oceanographic (METOC) information to enhance effective employment of battlefield forces. Of critical importance to providing METOC theater information is the generation of meteorological parameters produced by numerical prediction models and application software at the Air Force Global Weather Central (AFGWC), Offutt Air Force Base, Nebraska. Ultimately, application-derived data will be produced by the regional Joint METOC Forecast Units and by the deployed teams within a theater. The USAF Air Staff contracted with Argonne National Laboratory (ANL) for assistance in defining a hardware and software solution using off-the-shelf technology that would give the USAF the flexibility of testing various meteorological models and the ability to use the system within their daily operational constraints.

  18. In-air ion beam analysis with high spatial resolution proton microbeam

    NASA Astrophysics Data System (ADS)

    Jakšić, M.; Chokheli, D.; Fazinić, S.; Grilj, V.; Skukan, N.; Sudić, I.; Tadić, T.; Antičić, T.

    2016-03-01

    One of the possible ways to maintain the micrometre spatial resolution while performing ion beam analysis in the air is to increase the energy of ions. In order to explore capabilities and limitations of this approach, we have tested a range of proton beam energies (2-6 MeV) using in-air STIM (Scanning Ion Transmission Microscopy) setup. Measurements of the spatial resolution dependence on proton energy have been compared with SRIM simulation and modelling of proton multiple scattering by different approaches. Results were used to select experimental conditions in which 1 micrometre spatial resolution could be obtained. High resolution in-air microbeam could be applied for IBIC (Ion Beam Induced Charge) tests of large detectors used in nuclear and high energy physics that otherwise cannot be tested in relatively small microbeam vacuum chambers.

  19. Analysis of bacterial detachment from substratum surfaces by the passage of air-liquid interfaces.

    PubMed

    Gómez-Suárez, C; Busscher, H J; van der Mei, H C

    2001-06-01

    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 x 10(6) 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

  20. 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

  1. 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.

  2. 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.

  3. Robustness analysis of an air heating plant and control law by using polynomial chaos

    NASA Astrophysics Data System (ADS)

    Colón, Diego; Ferreira, Murillo A. S.; Balthazar, José M.; Bueno, Átila M.; de S. R. F. Rosa, Suélia

    2014-12-01

    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.

  4. Data Quality Objectives for Regulatory Requirements for Hazardous and Radioactive Air Emissions Sampling and Analysis

    SciTech Connect

    MULKEY, C.H.

    1999-07-06

    This document describes the results of the data quality objective (DQO) process undertaken to define data needs for state and federal requirements associated with toxic, hazardous, and/or radiological air emissions under the jurisdiction of the River Protection Project (RPP). Hereafter, this document is referred to as the Air DQO. The primary drivers for characterization under this DQO are the regulatory requirements pursuant to Washington State regulations, that may require sampling and analysis. The federal regulations concerning air emissions are incorporated into the Washington State regulations. Data needs exist for nonradioactive and radioactive waste constituents and characteristics as identified through the DQO process described in this document. The purpose is to identify current data needs for complying with regulatory drivers for the measurement of air emissions from RPP facilities in support of air permitting. These drivers include best management practices; similar analyses may have more than one regulatory driver. This document should not be used for determining overall compliance with regulations because the regulations are in constant change, and this document may not reflect the latest regulatory requirements. Regulatory requirements are also expected to change as various permits are issued. Data needs require samples for both radionuclides and nonradionuclide analytes of air emissions from tanks and stored waste containers. The collection of data is to support environmental permitting and compliance, not for health and safety issues. This document does not address health or safety regulations or requirements (those of the Occupational Safety and Health Administration or the National Institute of Occupational Safety and Health) or continuous emission monitoring systems. This DQO is applicable to all equipment, facilities, and operations under the jurisdiction of RPP that emit or have the potential to emit regulated air pollutants.

  5. Indispensable Resources for Institutional Researchers: An Analysis of AIR Publication Topics Since 1974. AIR 1997 Annual Forum Paper.

    ERIC Educational Resources Information Center

    Volkwein, J. Fredericks

    This study identified and classified the Association for Institutional Research (AIR) publication topics and authors since 1973 in order to provide a reference resource for institutional researchers. The study reviewed the following AIR publication collections: "Research in Higher Education"; "New Directions for Institutional Research"; "Resources…

  6. Genetic Variation in the TP53 Pathway and Bladder Cancer Risk. A Comprehensive Analysis

    PubMed Central

    Pineda, Silvia; Milne, Roger L.; Calle, M. Luz; Rothman, Nathaniel; López de Maturana, Evangelina; Herranz, Jesús; Kogevinas, Manolis; Chanock, Stephen J.; Tardón, Adonina; Márquez, Mirari; Guey, Lin T.; García-Closas, Montserrat; Lloreta, Josep; Baum, Erin; González-Neira, Anna; Carrato, Alfredo; Navarro, Arcadi; Silverman, Debra T.; Real, Francisco X.; Malats, Núria

    2014-01-01

    Introduction Germline variants in TP63 have been consistently associated with several tumors, including bladder cancer, indicating the importance of TP53 pathway in cancer genetic susceptibility. However, variants in other related genes, including TP53 rs1042522 (Arg72Pro), still present controversial results. We carried out an in depth assessment of associations between common germline variants in the TP53 pathway and bladder cancer risk. Material and Methods We investigated 184 tagSNPs from 18 genes in 1,058 cases and 1,138 controls from the Spanish Bladder Cancer/EPICURO Study. Cases were newly-diagnosed bladder cancer patients during 1998–2001. Hospital controls were age-gender, and area matched to cases. SNPs were genotyped in blood DNA using Illumina Golden Gate and TaqMan assays. Cases were subphenotyped according to stage/grade and tumor p53 expression. We applied classical tests to assess individual SNP associations and the Least Absolute Shrinkage and Selection Operator (LASSO)-penalized logistic regression analysis to assess multiple SNPs simultaneously. Results Based on classical analyses, SNPs in BAK1 (1), IGF1R (5), P53AIP1 (1), PMAIP1 (2), SERINPB5 (3), TP63 (3), and TP73 (1) showed significant associations at p-value≤0.05. However, no evidence of association, either with overall risk or with specific disease subtypes, was observed after correction for multiple testing (p-value≥0.8). LASSO selected the SNP rs6567355 in SERPINB5 with 83% of reproducibility. This SNP provided an OR = 1.21, 95%CI 1.05–1.38, p-value = 0.006, and a corrected p-value = 0.5 when controlling for over-estimation. Discussion We found no strong evidence that common variants in the TP53 pathway are associated with bladder cancer susceptibility. Our study suggests that it is unlikely that TP53 Arg72Pro is implicated in the UCB in white Europeans. SERPINB5 and TP63 variation deserve further exploration in extended studies. PMID:24818791

  7. Silver Valley lead study: further analysis of the relationship between blood lead and air lead

    SciTech Connect

    Snee, R.D.

    1982-02-01

    Blood lead and air lead levels of children who lived within 32 km of a smelter in Kellogg, ID were measured in 1974 and 1975. While an analysis of the 1974 survey has appeared, the results of the 1975 survey and an evaluation of the change in blood lead levels of those children who participated in both the 1974 and 1975 surveys has not previously been discussed in the literature. It is concluded that, for these data, in the air lead range of 0.5-5 ..mu..g/m/sup 3/, the blood lead-air lead relationship can be adequately described by blood lead-air lead slope which is approximately 1.0 and at most 1.4. This slope was also found to be independent of children's age. It is shown that an accurate estimate of the blood lead-air lead relationship cannot be obtained without taking proper account of selected environmental variables; specifically, pica, sex, age, father's work status, education, and home cleanliness.

  8. Air quality impact analysis in support of the new production reactor environmental impact statement

    SciTech Connect

    Hadley, D L

    1991-04-01

    The Pacific Northwest Laboratory (PNL) conducted this air quality impact analysis for the US Department of Energy (DOE). The purpose of this work was to provide Argonne National Laboratory (ANL) with the required estimates of ground-level concentrations of five criteria air pollutants at the Hanford Site boundary from each of the