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Sample records for pathway analysis method

  1. A strategy for evaluating pathway analysis methods.

    Science.gov (United States)

    Yu, Chenggang; Woo, Hyung Jun; Yu, Xueping; Oyama, Tatsuya; Wallqvist, Anders; Reifman, Jaques

    2017-10-13

    Researchers have previously developed a multitude of methods designed to identify biological pathways associated with specific clinical or experimental conditions of interest, with the aim of facilitating biological interpretation of high-throughput data. Before practically applying such pathway analysis (PA) methods, we must first evaluate their performance and reliability, using datasets where the pathways perturbed by the conditions of interest have been well characterized in advance. However, such 'ground truths' (or gold standards) are often unavailable. Furthermore, previous evaluation strategies that have focused on defining 'true answers' are unable to systematically and objectively assess PA methods under a wide range of conditions. In this work, we propose a novel strategy for evaluating PA methods independently of any gold standard, either established or assumed. The strategy involves the use of two mutually complementary metrics, recall and discrimination. Recall measures the consistency of the perturbed pathways identified by applying a particular analysis method to an original large dataset and those identified by the same method to a sub-dataset of the original dataset. In contrast, discrimination measures specificity-the degree to which the perturbed pathways identified by a particular method to a dataset from one experiment differ from those identifying by the same method to a dataset from a different experiment. We used these metrics and 24 datasets to evaluate six widely used PA methods. The results highlighted the common challenge in reliably identifying significant pathways from small datasets. Importantly, we confirmed the effectiveness of our proposed dual-metric strategy by showing that previous comparative studies corroborate the performance evaluations of the six methods obtained by our strategy. Unlike any previously proposed strategy for evaluating the performance of PA methods, our dual-metric strategy does not rely on any ground truth

  2. Cleanup standards and pathways analysis methods

    International Nuclear Information System (INIS)

    Devgun, J.S.

    1993-01-01

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

  3. Pathway analysis for alternate low-level waste disposal methods

    International Nuclear Information System (INIS)

    Rao, R.R.; Kozak, M.W.; McCord, J.T.; Olague, N.E.

    1992-01-01

    The purpose of this paper is to evaluate a complete set of environmental pathways for disposal options and conditions that the Nuclear Regulatory Commission (NRC) may analyze for a low-level radioactive waste (LLW) license application. The regulations pertaining In the past, shallow-land burial has been used for the disposal of low-level radioactive waste. However, with the advent of the State Compact system of LLW disposal, many alternative technologies may be used. The alternative LLW disposal facilities include below- ground vault, tumulus, above-ground vault, shaft, and mine disposal This paper will form the foundation of an update of the previously developed Sandia National Laboratories (SNL)/NRC LLW performance assessment methodology. Based on the pathway assessment for alternative disposal methods, a determination will be made about whether the current methodology can satisfactorily analyze the pathways and phenomena likely to be important for the full range of potential disposal options. We have attempted to be conservative in keeping pathways in the lists that may usually be of marginal importance. In this way we can build confidence that we have spanned the range of cases likely to be encountered at a real site. Results of the pathway assessment indicate that disposal methods can be categorized in groupings based on their depth of disposal. For the deep disposal options of shaft and mine disposal, the key pathways are identical. The shallow disposal options, such as tumulus, shallow-land, and below-ground vault disposal also may be grouped together from a pathway analysis perspective. Above-ground vault disposal cannot be grouped with any of the other disposal options. The pathway analysis shows a definite trend concerning depth of disposal. The above-ground option has the largest number of significant pathways. As the waste becomes more isolated, the number of significant pathways is reduced. Similar to shallow-land burial, it was found that for all

  4. Pathways of topological rank analysis (PoTRA): a novel method to detect pathways involved in hepatocellular carcinoma.

    Science.gov (United States)

    Li, Chaoxing; Liu, Li; Dinu, Valentin

    2018-01-01

    Complex diseases such as cancer are usually the result of a combination of environmental factors and one or several biological pathways consisting of sets of genes. Each biological pathway exerts its function by delivering signaling through the gene network. Theoretically, a pathway is supposed to have a robust topological structure under normal physiological conditions. However, the pathway's topological structure could be altered under some pathological condition. It is well known that a normal biological network includes a small number of well-connected hub nodes and a large number of nodes that are non-hubs. In addition, it is reported that the loss of connectivity is a common topological trait of cancer networks, which is an assumption of our method. Hence, from normal to cancer, the process of the network losing connectivity might be the process of disrupting the structure of the network, namely, the number of hub genes might be altered in cancer compared to that in normal or the distribution of topological ranks of genes might be altered. Based on this, we propose a new PageRank-based method called Pathways of Topological Rank Analysis (PoTRA) to detect pathways involved in cancer. We use PageRank to measure the relative topological ranks of genes in each biological pathway, then select hub genes for each pathway, and use Fisher's exact test to test if the number of hub genes in each pathway is altered from normal to cancer. Alternatively, if the distribution of topological ranks of gene in a pathway is altered between normal and cancer, this pathway might also be involved in cancer. Hence, we use the Kolmogorov-Smirnov test to detect pathways that have an altered distribution of topological ranks of genes between two phenotypes. We apply PoTRA to study hepatocellular carcinoma (HCC) and several subtypes of HCC. Very interestingly, we discover that all significant pathways in HCC are cancer-associated generally, while several significant pathways in subtypes

  5. Pathways of topological rank analysis (PoTRA: a novel method to detect pathways involved in hepatocellular carcinoma

    Directory of Open Access Journals (Sweden)

    Chaoxing Li

    2018-04-01

    Full Text Available Complex diseases such as cancer are usually the result of a combination of environmental factors and one or several biological pathways consisting of sets of genes. Each biological pathway exerts its function by delivering signaling through the gene network. Theoretically, a pathway is supposed to have a robust topological structure under normal physiological conditions. However, the pathway’s topological structure could be altered under some pathological condition. It is well known that a normal biological network includes a small number of well-connected hub nodes and a large number of nodes that are non-hubs. In addition, it is reported that the loss of connectivity is a common topological trait of cancer networks, which is an assumption of our method. Hence, from normal to cancer, the process of the network losing connectivity might be the process of disrupting the structure of the network, namely, the number of hub genes might be altered in cancer compared to that in normal or the distribution of topological ranks of genes might be altered. Based on this, we propose a new PageRank-based method called Pathways of Topological Rank Analysis (PoTRA to detect pathways involved in cancer. We use PageRank to measure the relative topological ranks of genes in each biological pathway, then select hub genes for each pathway, and use Fisher’s exact test to test if the number of hub genes in each pathway is altered from normal to cancer. Alternatively, if the distribution of topological ranks of gene in a pathway is altered between normal and cancer, this pathway might also be involved in cancer. Hence, we use the Kolmogorov–Smirnov test to detect pathways that have an altered distribution of topological ranks of genes between two phenotypes. We apply PoTRA to study hepatocellular carcinoma (HCC and several subtypes of HCC. Very interestingly, we discover that all significant pathways in HCC are cancer-associated generally, while several

  6. TEGS-CN: A Statistical Method for Pathway Analysis of Genome-wide Copy Number Profile.

    Science.gov (United States)

    Huang, Yen-Tsung; Hsu, Thomas; Christiani, David C

    2014-01-01

    The effects of copy number alterations make up a significant part of the tumor genome profile, but pathway analyses of these alterations are still not well established. We proposed a novel method to analyze multiple copy numbers of genes within a pathway, termed Test for the Effect of a Gene Set with Copy Number data (TEGS-CN). TEGS-CN was adapted from TEGS, a method that we previously developed for gene expression data using a variance component score test. With additional development, we extend the method to analyze DNA copy number data, accounting for different sizes and thus various numbers of copy number probes in genes. The test statistic follows a mixture of X (2) distributions that can be obtained using permutation with scaled X (2) approximation. We conducted simulation studies to evaluate the size and the power of TEGS-CN and to compare its performance with TEGS. We analyzed a genome-wide copy number data from 264 patients of non-small-cell lung cancer. With the Molecular Signatures Database (MSigDB) pathway database, the genome-wide copy number data can be classified into 1814 biological pathways or gene sets. We investigated associations of the copy number profile of the 1814 gene sets with pack-years of cigarette smoking. Our analysis revealed five pathways with significant P values after Bonferroni adjustment (number data, and causal mechanisms of the five pathways require further study.

  7. Following User Pathways: Cross Platform and Mixed Methods Analysis in Social Media Studies

    DEFF Research Database (Denmark)

    Hall, Margeret; Mazarakis, Athanasios; Peters, Isabella

    2016-01-01

    is the mixed method approach (e.g. qualitative and quantitative methods) in order to better understand how users and society interacts online. The workshop 'Following User Pathways' brings together a community of researchers and professionals to address methodological, analytical, conceptual, and technological......Social media and the resulting tidal wave of available data have changed the ways and methods researchers analyze communities at scale. But the full potential for social scientists (and others) is not yet achieved. Despite the popularity of social media analysis in the past decade, few researchers...... challenges and opportunities of cross-platform, mixed method analysis in social media ecosystems....

  8. Phytohormone signaling pathway analysis method for comparing hormone responses in plant-pest interactions

    Directory of Open Access Journals (Sweden)

    Studham Matthew E

    2012-07-01

    Full Text Available Abstract Background Phytohormones mediate plant defense responses to pests and pathogens. In particular, the hormones jasmonic acid, ethylene, salicylic acid, and abscisic acid have been shown to dictate and fine-tune defense responses, and identification of the phytohormone components of a particular defense response is commonly used to characterize it. Identification of phytohormone regulation is particularly important in transcriptome analyses. Currently there is no computational tool to determine the relative activity of these hormones that can be applied to transcriptome analyses in soybean. Findings We developed a pathway analysis method that provides a broad measure of the activation or suppression of individual phytohormone pathways based on changes in transcript expression of pathway-related genes. The magnitude and significance of these changes are used to determine a pathway score for a phytohormone for a given comparison in a microarray experiment. Scores for individual hormones can then be compared to determine the dominant phytohormone in a given defense response. To validate this method, it was applied to publicly available data from previous microarray experiments that studied the response of soybean plants to Asian soybean rust and soybean cyst nematode. The results of the analyses for these experiments agreed with our current understanding of the role of phytohormones in these defense responses. Conclusions This method is useful in providing a broad measure of the relative induction and suppression of soybean phytohormones during a defense response. This method could be used as part of microarray studies that include individual transcript analysis, gene set analysis, and other methods for a comprehensive defense response characterization.

  9. Methods of analysis of the membrane trafficking pathway from recycling endosomes to lysosomes.

    Science.gov (United States)

    Matsui, Takahide; Fukuda, Mitsunori

    2014-01-01

    The transferrin receptor (TfR) is responsible for iron uptake through its trafficking between the plasma membrane and recycling endosomes, and as a result it has become a well-known marker for recycling endosomes. Although the molecular basis of the TfR recycling pathway has been thoroughly investigated, the TfR degradation mechanism has been poorly understood. Exposure of cultured cells to two drugs, the protein synthesis inhibitor cycloheximide and the V-ATPase inhibitor bafilomycin A1, recently showed that TfR is not only recycled back to the plasma membrane after endocytosis but is constitutively transported to lysosomes for degradation. The results of genome-wide screening of mouse Rab small GTPases (common regulators of membrane trafficking in all eukaryotes) have indicated that Rab12 regulates TfR trafficking to lysosomes independently of the known membrane trafficking pathways, for example, the conventional endocytic pathway and recycling pathway. This chapter summarizes the methods that the authors used to analyze the membrane trafficking pathway from recycling endosomes to lysosomes that is specifically regulated by Rab12. © 2014 Elsevier Inc. All rights reserved.

  10. DMPD: The Toll-like receptors: analysis by forward genetic methods. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 16001129 The Toll-like receptors: analysis by forward genetic methods. Beutler B. I...mmunogenetics. 2005 Jul;57(6):385-92. (.png) (.svg) (.html) (.csml) Show The Toll-like receptors: analysis by forwar...d genetic methods. PubmedID 16001129 Title The Toll-like receptors: analysis by forward genetic meth

  11. Pathway analysis of IMC

    DEFF Research Database (Denmark)

    Skrypnyuk, Nataliya; Nielson, Flemming; Pilegaard, Henrik

    2009-01-01

    We present the ongoing work on the pathway analysis of a stochastic calculus. Firstly we present a particular stochastic calculus that we have chosen for our modeling - the Interactive Markov Chains calculus, IMC for short. After that we specify a few restrictions that we have introduced into the...... into the syntax of IMC in order to make our analysis feasible. Finally we describe the analysis itself together with several theoretical results that we have proved for it.......We present the ongoing work on the pathway analysis of a stochastic calculus. Firstly we present a particular stochastic calculus that we have chosen for our modeling - the Interactive Markov Chains calculus, IMC for short. After that we specify a few restrictions that we have introduced...

  12. Machine Learning Methods for Analysis of Metabolic Data and Metabolic Pathway Modeling.

    Science.gov (United States)

    Cuperlovic-Culf, Miroslava

    2018-01-11

    Machine learning uses experimental data to optimize clustering or classification of samples or features, or to develop, augment or verify models that can be used to predict behavior or properties of systems. It is expected that machine learning will help provide actionable knowledge from a variety of big data including metabolomics data, as well as results of metabolism models. A variety of machine learning methods has been applied in bioinformatics and metabolism analyses including self-organizing maps, support vector machines, the kernel machine, Bayesian networks or fuzzy logic. To a lesser extent, machine learning has also been utilized to take advantage of the increasing availability of genomics and metabolomics data for the optimization of metabolic network models and their analysis. In this context, machine learning has aided the development of metabolic networks, the calculation of parameters for stoichiometric and kinetic models, as well as the analysis of major features in the model for the optimal application of bioreactors. Examples of this very interesting, albeit highly complex, application of machine learning for metabolism modeling will be the primary focus of this review presenting several different types of applications for model optimization, parameter determination or system analysis using models, as well as the utilization of several different types of machine learning technologies.

  13. Machine Learning Methods for Analysis of Metabolic Data and Metabolic Pathway Modeling

    Science.gov (United States)

    Cuperlovic-Culf, Miroslava

    2018-01-01

    Machine learning uses experimental data to optimize clustering or classification of samples or features, or to develop, augment or verify models that can be used to predict behavior or properties of systems. It is expected that machine learning will help provide actionable knowledge from a variety of big data including metabolomics data, as well as results of metabolism models. A variety of machine learning methods has been applied in bioinformatics and metabolism analyses including self-organizing maps, support vector machines, the kernel machine, Bayesian networks or fuzzy logic. To a lesser extent, machine learning has also been utilized to take advantage of the increasing availability of genomics and metabolomics data for the optimization of metabolic network models and their analysis. In this context, machine learning has aided the development of metabolic networks, the calculation of parameters for stoichiometric and kinetic models, as well as the analysis of major features in the model for the optimal application of bioreactors. Examples of this very interesting, albeit highly complex, application of machine learning for metabolism modeling will be the primary focus of this review presenting several different types of applications for model optimization, parameter determination or system analysis using models, as well as the utilization of several different types of machine learning technologies. PMID:29324649

  14. A novel method to identify hub pathways of rheumatoid arthritis based on differential pathway networks.

    Science.gov (United States)

    Wei, Shi-Tong; Sun, Yong-Hua; Zong, Shi-Hua

    2017-09-01

    The aim of the current study was to identify hub pathways of rheumatoid arthritis (RA) using a novel method based on differential pathway network (DPN) analysis. The present study proposed a DPN where protein‑protein interaction (PPI) network was integrated with pathway‑pathway interactions. Pathway data was obtained from background PPI network and the Reactome pathway database. Subsequently, pathway interactions were extracted from the pathway data by building randomized gene‑gene interactions and a weight value was assigned to each pathway interaction using Spearman correlation coefficient (SCC) to identify differential pathway interactions. Differential pathway interactions were visualized using Cytoscape to construct a DPN. Topological analysis was conducted to identify hub pathways that possessed the top 5% degree distribution of DPN. Modules of DPN were mined according to ClusterONE. A total of 855 pathways were selected to build pathway interactions. By filtrating pathway interactions of weight values >0.7, a DPN with 312 nodes and 791 edges was obtained. Topological degree analysis revealed 15 hub pathways, such as heparan sulfate/heparin‑glycosaminoglycan (HS‑GAG) degradation, HS‑GAG metabolism and keratan sulfate degradation for RA based on DPN. Furthermore, hub pathways were also important in modules, which validated the significance of hub pathways. In conclusion, the proposed method is a computationally efficient way to identify hub pathways of RA, which identified 15 hub pathways that may be potential biomarkers and provide insight to future investigation and treatment of RA.

  15. Pathways to Lean Software Development: An Analysis of Effective Methods of Change

    Science.gov (United States)

    Hanson, Richard D.

    2014-01-01

    This qualitative Delphi study explored the challenges that exist in delivering software on time, within budget, and with the original scope identified. The literature review identified many attempts over the past several decades to reform the methods used to develop software. These attempts found that the classical waterfall method, which is…

  16. Pathways to lean software development: An analysis of effective methods of change

    Science.gov (United States)

    Hanson, Richard D.

    This qualitative Delphi study explored the challenges that exist in delivering software on time, within budget, and with the original scope identified. The literature review identified many attempts over the past several decades to reform the methods used to develop software. These attempts found that the classical waterfall method, which is firmly entrenched in American business today was to blame for this difficulty (Chatterjee, 2010). Each of these proponents of new methods sought to remove waste, lighten out the process, and implement lean principles in software development. Through this study, the experts evaluated the barriers to effective development principles and defined leadership qualities necessary to overcome these barriers. The barriers identified were issues of resistance to change, risk and reward issues, and management buy-in. Thirty experts in software development from several Fortune 500 companies across the United States explored each of these issues in detail. The conclusion reached by these experts was that visionary leadership is necessary to overcome these challenges.

  17. Data driven linear algebraic methods for analysis of molecular pathways: application to disease progression in shock/trauma.

    Science.gov (United States)

    McGuire, Mary F; Sriram Iyengar, M; Mercer, David W

    2012-04-01

    Although trauma is the leading cause of death for those below 45years of age, there is a dearth of information about the temporal behavior of the underlying biological mechanisms in those who survive the initial trauma only to later suffer from syndromes such as multiple organ failure. Levels of serum cytokines potentially affect the clinical outcomes of trauma; understanding how cytokine levels modulate intra-cellular signaling pathways can yield insights into molecular mechanisms of disease progression and help to identify targeted therapies. However, developing such analyses is challenging since it necessitates the integration and interpretation of large amounts of heterogeneous, quantitative and qualitative data. Here we present the Pathway Semantics Algorithm (PSA), an algebraic process of node and edge analyses of evoked biological pathways over time for in silico discovery of biomedical hypotheses, using data from a prospective controlled clinical study of the role of cytokines in multiple organ failure (MOF) at a major US trauma center. A matrix algebra approach was used in both the PSA node and PSA edge analyses with different matrix configurations and computations based on the biomedical questions to be examined. In the edge analysis, a percentage measure of crosstalk called XTALK was also developed to assess cross-pathway interference. In the node/molecular analysis of the first 24h from trauma, PSA uncovered seven molecules evoked computationally that differentiated outcomes of MOF or non-MOF (NMOF), of which three molecules had not been previously associated with any shock/trauma syndrome. In the edge/molecular interaction analysis, PSA examined four categories of functional molecular interaction relationships--activation, expression, inhibition, and transcription--and found that the interaction patterns and crosstalk changed over time and outcome. The PSA edge analysis suggests that a diagnosis, prognosis or therapy based on molecular interaction

  18. Pathway cross-talk network analysis identifies critical pathways in neonatal sepsis.

    Science.gov (United States)

    Meng, Yu-Xiu; Liu, Quan-Hong; Chen, Deng-Hong; Meng, Ying

    2017-06-01

    Despite advances in neonatal care, sepsis remains a major cause of morbidity and mortality in neonates worldwide. Pathway cross-talk analysis might contribute to the inference of the driving forces in bacterial sepsis and facilitate a better understanding of underlying pathogenesis of neonatal sepsis. This study aimed to explore the critical pathways associated with the progression of neonatal sepsis by the pathway cross-talk analysis. By integrating neonatal transcriptome data with known pathway data and protein-protein interaction data, we systematically uncovered the disease pathway cross-talks and constructed a disease pathway cross-talk network for neonatal sepsis. Then, attract method was employed to explore the dysregulated pathways associated with neonatal sepsis. To determine the critical pathways in neonatal sepsis, rank product (RP) algorithm, centrality analysis and impact factor (IF) were introduced sequentially, which synthetically considered the differential expression of genes and pathways, pathways cross-talks and pathway parameters in the network. The dysregulated pathways with the highest IF values as well as RPpathways in neonatal sepsis. By integrating three kinds of data, only 6919 common genes were included to perform the pathway cross-talk analysis. By statistic analysis, a total of 1249 significant pathway cross-talks were selected to construct the pathway cross-talk network. Moreover, 47 dys-regulated pathways were identified via attract method, 20 pathways were identified under RPpathways with the highest IF were also screened from the pathway cross-talk network. Among them, we selected 8 common pathways, i.e. critical pathways. In this study, we systematically tracked 8 critical pathways involved in neonatal sepsis by integrating attract method and pathway cross-talk network. These pathways might be responsible for the host response in infection, and of great value for advancing diagnosis and therapy of neonatal sepsis. Copyright © 2017

  19. Pathway Interaction Network Analysis Identifies Dysregulated Pathways in Human Monocytes Infected by Listeria monocytogenes

    Directory of Open Access Journals (Sweden)

    Wufeng Fan

    2017-01-01

    Full Text Available In our study, we aimed to extract dysregulated pathways in human monocytes infected by Listeria monocytogenes (LM based on pathway interaction network (PIN which presented the functional dependency between pathways. After genes were aligned to the pathways, principal component analysis (PCA was used to calculate the pathway activity for each pathway, followed by detecting seed pathway. A PIN was constructed based on gene expression profile, protein-protein interactions (PPIs, and cellular pathways. Identifying dysregulated pathways from the PIN was performed relying on seed pathway and classification accuracy. To evaluate whether the PIN method was feasible or not, we compared the introduced method with standard network centrality measures. The pathway of RNA polymerase II pretranscription events was selected as the seed pathway. Taking this seed pathway as start, one pathway set (9 dysregulated pathways with AUC score of 1.00 was identified. Among the 5 hub pathways obtained using standard network centrality measures, 4 pathways were the common ones between the two methods. RNA polymerase II transcription and DNA replication owned a higher number of pathway genes and DEGs. These dysregulated pathways work together to influence the progression of LM infection, and they will be available as biomarkers to diagnose LM infection.

  20. Machine learning methods for metabolic pathway prediction

    Directory of Open Access Journals (Sweden)

    Karp Peter D

    2010-01-01

    Full Text Available Abstract Background A key challenge in systems biology is the reconstruction of an organism's metabolic network from its genome sequence. One strategy for addressing this problem is to predict which metabolic pathways, from a reference database of known pathways, are present in the organism, based on the annotated genome of the organism. Results To quantitatively validate methods for pathway prediction, we developed a large "gold standard" dataset of 5,610 pathway instances known to be present or absent in curated metabolic pathway databases for six organisms. We defined a collection of 123 pathway features, whose information content we evaluated with respect to the gold standard. Feature data were used as input to an extensive collection of machine learning (ML methods, including naïve Bayes, decision trees, and logistic regression, together with feature selection and ensemble methods. We compared the ML methods to the previous PathoLogic algorithm for pathway prediction using the gold standard dataset. We found that ML-based prediction methods can match the performance of the PathoLogic algorithm. PathoLogic achieved an accuracy of 91% and an F-measure of 0.786. The ML-based prediction methods achieved accuracy as high as 91.2% and F-measure as high as 0.787. The ML-based methods output a probability for each predicted pathway, whereas PathoLogic does not, which provides more information to the user and facilitates filtering of predicted pathways. Conclusions ML methods for pathway prediction perform as well as existing methods, and have qualitative advantages in terms of extensibility, tunability, and explainability. More advanced prediction methods and/or more sophisticated input features may improve the performance of ML methods. However, pathway prediction performance appears to be limited largely by the ability to correctly match enzymes to the reactions they catalyze based on genome annotations.

  1. Machine learning methods for metabolic pathway prediction

    Science.gov (United States)

    2010-01-01

    Background A key challenge in systems biology is the reconstruction of an organism's metabolic network from its genome sequence. One strategy for addressing this problem is to predict which metabolic pathways, from a reference database of known pathways, are present in the organism, based on the annotated genome of the organism. Results To quantitatively validate methods for pathway prediction, we developed a large "gold standard" dataset of 5,610 pathway instances known to be present or absent in curated metabolic pathway databases for six organisms. We defined a collection of 123 pathway features, whose information content we evaluated with respect to the gold standard. Feature data were used as input to an extensive collection of machine learning (ML) methods, including naïve Bayes, decision trees, and logistic regression, together with feature selection and ensemble methods. We compared the ML methods to the previous PathoLogic algorithm for pathway prediction using the gold standard dataset. We found that ML-based prediction methods can match the performance of the PathoLogic algorithm. PathoLogic achieved an accuracy of 91% and an F-measure of 0.786. The ML-based prediction methods achieved accuracy as high as 91.2% and F-measure as high as 0.787. The ML-based methods output a probability for each predicted pathway, whereas PathoLogic does not, which provides more information to the user and facilitates filtering of predicted pathways. Conclusions ML methods for pathway prediction perform as well as existing methods, and have qualitative advantages in terms of extensibility, tunability, and explainability. More advanced prediction methods and/or more sophisticated input features may improve the performance of ML methods. However, pathway prediction performance appears to be limited largely by the ability to correctly match enzymes to the reactions they catalyze based on genome annotations. PMID:20064214

  2. Using a multi-method, user centred, prospective hazard analysis to assess care quality and patient safety in a care pathway

    Directory of Open Access Journals (Sweden)

    Escoto Kamisha

    2007-06-01

    Full Text Available Abstract Background Care pathways can be complex, often involving multiple care providers and as such are recognised as containing multiple opportunities for error. Prospective hazard analysis methods may be useful for evaluating care provided across primary and secondary care pathway boundaries. These methods take into account the views of users (staff and patients when determining where potential hazards may lie. The aim of this study is to evaluate the feasibility of prospective hazard analysis methods when assessing quality and safety in care pathways that lie across primary and secondary care boundaries. Methods Development of a process map of the care pathway for patients entering into a Chronic Obstructive Pulmonary Disease (COPD supported discharge programme. Triangulation of information from: care process mapping, semi-structured interviews with COPD patients, semi-structured interviews with COPD staff, two round modified Delphi study and review of prioritised quality and safety challenges by health care staff. Results Interview themes emerged under the headings of quality of care and patient safety. Quality and safety concerns were mostly raised in relation to communication, for example, communication with other hospital teams. The three highest ranked safety concerns from the modified Delphi review were: difficulties in accessing hospital records, information transfer to primary care and failure to communicate medication changes to primary care. Conclusion This study has demonstrated the feasibility of using mixed methods to review the quality and safety of care in a care pathway. By using multiple research methods it was possible to get a clear picture of service quality variations and also to demonstrate which points in the care pathway had real potential for patient safety incidents or system failures to occur. By using these methods to analyse one condition specific care pathway it was possible to uncover a number of hospital

  3. Simplified analysis for liquid pathway studies

    International Nuclear Information System (INIS)

    Codell, R.B.

    1984-08-01

    The analysis of the potential contamination of surface water via groundwater contamination from severe nuclear accidents is routinely calculated during licensing reviews. This analysis is facilitated by the methods described in this report, which is codified into a BASIC language computer program, SCREENLP. This program performs simplified calculations for groundwater and surface water transport and calculates population doses to potential users for the contaminated water irrespective of possible mitigation methods. The results are then compared to similar analyses performed using data for the generic sites in NUREG-0440, Liquid Pathway Generic Study, to determine if the site being investigated would pose any unusual liquid pathway hazards

  4. Pathway analysis: State of the art

    Directory of Open Access Journals (Sweden)

    Miguel Angel eGarcía-Campos

    2015-12-01

    Full Text Available 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.

  5. Method for determining heterologous biosynthesis pathways

    KAUST Repository

    Gao, Xin

    2017-08-10

    The present invention relates to a method and system for dynamically analyzing, determining, predicting and displaying ranked suitable heterologous biosynthesis pathways for a specified host. The present invention addresses the problem of finding suitable pathways for the endogenous metabolism of a host organism because the efficacy of heterologous biosynthesis is affected by competing endogenous pathways. The present invention is called MRE (Metabolic Route Explorer), and it was conceived and developed to systematically and dynamically search for, determine, analyze, and display promising heterologous pathways while considering competing endogenous reactions in a given host organism.

  6. A novel dysregulated pathway-identification analysis based on global influence of within-pathway effects and crosstalk between pathways

    Science.gov (United States)

    Han, Junwei; Li, Chunquan; Yang, Haixiu; Xu, Yanjun; Zhang, Chunlong; Ma, Jiquan; Shi, Xinrui; Liu, Wei; Shang, Desi; Yao, Qianlan; Zhang, Yunpeng; Su, Fei; Feng, Li; Li, Xia

    2015-01-01

    Identifying dysregulated pathways from high-throughput experimental data in order to infer underlying biological insights is an important task. Current pathway-identification methods focus on single pathways in isolation; however, consideration of crosstalk between pathways could improve our understanding of alterations in biological states. We propose a novel method of pathway analysis based on global influence (PAGI) to identify dysregulated pathways, by considering both within-pathway effects and crosstalk between pathways. We constructed a global gene–gene network based on the relationships among genes extracted from a pathway database. We then evaluated the extent of differential expression for each gene, and mapped them to the global network. The random walk with restart algorithm was used to calculate the extent of genes affected by global influence. Finally, we used cumulative distribution functions to determine the significance values of the dysregulated pathways. We applied the PAGI method to five cancer microarray datasets, and compared our results with gene set enrichment analysis and five other methods. Based on these analyses, we demonstrated that PAGI can effectively identify dysregulated pathways associated with cancer, with strong reproducibility and robustness. We implemented PAGI using the freely available R-based and Web-based tools (http://bioinfo.hrbmu.edu.cn/PAGI). PMID:25551156

  7. Pathway enrichment analysis approach based on topological structure and updated annotation of pathway.

    Science.gov (United States)

    Yang, Qian; Wang, Shuyuan; Dai, Enyu; Zhou, Shunheng; Liu, Dianming; Liu, Haizhou; Meng, Qianqian; Jiang, Bin; Jiang, Wei

    2017-08-16

    Pathway enrichment analysis has been widely used to identify cancer risk pathways, and contributes to elucidating the mechanism of tumorigenesis. However, most of the existing approaches use the outdated pathway information and neglect the complex gene interactions in pathway. Here, we first reviewed the existing widely used pathway enrichment analysis approaches briefly, and then, we proposed a novel topology-based pathway enrichment analysis (TPEA) method, which integrated topological properties and global upstream/downstream positions of genes in pathways. We compared TPEA with four widely used pathway enrichment analysis tools, including database for annotation, visualization and integrated discovery (DAVID), gene set enrichment analysis (GSEA), centrality-based pathway enrichment (CePa) and signaling pathway impact analysis (SPIA), through analyzing six gene expression profiles of three tumor types (colorectal cancer, thyroid cancer and endometrial cancer). As a result, we identified several well-known cancer risk pathways that could not be obtained by the existing tools, and the results of TPEA were more stable than that of the other tools in analyzing different data sets of the same cancer. Ultimately, we developed an R package to implement TPEA, which could online update KEGG pathway information and is available at the Comprehensive R Archive Network (CRAN): https://cran.r-project.org/web/packages/TPEA/. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  8. IPAD: the Integrated Pathway Analysis Database for Systematic Enrichment Analysis.

    Science.gov (United States)

    Zhang, Fan; Drabier, Renee

    2012-01-01

    multiple available data sources.IPAD is a comprehensive database covering about 22,498 genes, 25,469 proteins, 1956 pathways, 6704 diseases, 5615 drugs, and 52 organs integrated from databases including the BioCarta, KEGG, NCI-Nature curated, Reactome, CTD, PharmGKB, DrugBank, PharmGKB, and HOMER. The database has a web-based user interface that allows users to perform enrichment analysis from genes/proteins/molecules and inter-association analysis from a pathway, disease, drug, and organ.Moreover, the quality of the database was validated with the context of the existing biological knowledge and a "gold standard" constructed from reputable and reliable sources. Two case studies were also presented to demonstrate: 1) self-validation of enrichment analysis and inter-association analysis on brain-specific markers, and 2) identification of previously undiscovered components by the enrichment analysis from a prostate cancer study. IPAD is a new resource for analyzing, identifying, and validating pathway, disease, drug, organ specificity and their inter-associations. The statistical method we developed for enrichment and similarity measurement and the two criteria we described for setting the threshold parameters can be extended to other enrichment applications. Enriched pathways, diseases, drugs, organs and their inter-associations can be searched, displayed, and downloaded from our online user interface. The current IPAD database can help users address a wide range of biological pathway related, disease susceptibility related, drug target related and organ specificity related questions in human disease studies.

  9. Dysregulated Pathway Identification of Alzheimer's Disease Based on Internal Correlation Analysis of Genes and Pathways.

    Science.gov (United States)

    Kong, Wei; Mou, Xiaoyang; Di, Benteng; Deng, Jin; Zhong, Ruxing; Wang, Shuaiqun

    2017-11-20

    Dysregulated pathway identification is an important task which can gain insight into the underlying biological processes of disease. Current pathway-identification methods focus on a set of co-expression genes and single pathways and ignore the correlation between genes and pathways. The method proposed in this study, takes into account the internal correlations not only between genes but also pathways to identifying dysregulated pathways related to Alzheimer's disease (AD), the most common form of dementia. In order to find the significantly differential genes for AD, mutual information (MI) is used to measure interdependencies between genes other than expression valves. Then, by integrating the topology information from KEGG, the significant pathways involved in the feature genes are identified. Next, the distance correlation (DC) is applied to measure the pairwise pathway crosstalks since DC has the advantage of detecting nonlinear correlations when compared to Pearson correlation. Finally, the pathway pairs with significantly different correlations between normal and AD samples are known as dysregulated pathways. The molecular biology analysis demonstrated that many dysregulated pathways related to AD pathogenesis have been discovered successfully by the internal correlation detection. Furthermore, the insights of the dysregulated pathways in the development and deterioration of AD will help to find new effective target genes and provide important theoretical guidance for drug design. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  10. A systems biology approach for pathway level analysis

    OpenAIRE

    Draghici, Sorin; Khatri, Purvesh; Tarca, Adi Laurentiu; Amin, Kashyap; Done, Arina; Voichita, Calin; Georgescu, Constantin; Romero, Roberto

    2007-01-01

    A common challenge in the analysis of genomics data is trying to understand the underlying phenomenon in the context of all complex interactions taking place on various signaling pathways. A statistical approach using various models is universally used to identify the most relevant pathways in a given experiment. Here, we show that the existing pathway analysis methods fail to take into consideration important biological aspects and may provide incorrect results in certain situations. By usin...

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

    Science.gov (United States)

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

    2016-01-01

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

  12. Primary Metabolic Pathways and Metabolic Flux Analysis

    DEFF Research Database (Denmark)

    Villadsen, John

    2015-01-01

    his chapter introduces the metabolic flux analysis (MFA) or stoichiometry-based MFA, and describes the quantitative basis for MFA. It discusses the catabolic pathways in which free energy is produced to drive the cell-building anabolic pathways. An overview of these primary pathways provides...... the reader who is primarily trained in the engineering sciences with atleast a preliminary introduction to biochemistry and also shows how carbon is drained off the catabolic pathways to provide precursors for cell mass building and sometimes for important industrial products. The primary pathways...... to be examined in the following are: glycolysis, primarily by the EMP pathway, but other glycolytic pathways is also mentioned; fermentative pathways in which the redox generated in the glycolytic reactions are consumed; reactions in the tricarboxylic acid (TCA) cycle, which produce biomass precursors and redox...

  13. Comparative study on gene set and pathway topology-based enrichment methods.

    Science.gov (United States)

    Bayerlová, Michaela; Jung, Klaus; Kramer, Frank; Klemm, Florian; Bleckmann, Annalen; Beißbarth, Tim

    2015-10-22

    Enrichment analysis is a popular approach to identify pathways or sets of genes which are significantly enriched in the context of differentially expressed genes. The traditional gene set enrichment approach considers a pathway as a simple gene list disregarding any knowledge of gene or protein interactions. In contrast, the new group of so called pathway topology-based methods integrates the topological structure of a pathway into the analysis. We comparatively investigated gene set and pathway topology-based enrichment approaches, considering three gene set and four topological methods. These methods were compared in two extensive simulation studies and on a benchmark of 36 real datasets, providing the same pathway input data for all methods. In the benchmark data analysis both types of methods showed a comparable ability to detect enriched pathways. The first simulation study was conducted with KEGG pathways, which showed considerable gene overlaps between each other. In this study with original KEGG pathways, none of the topology-based methods outperformed the gene set approach. Therefore, a second simulation study was performed on non-overlapping pathways created by unique gene IDs. Here, methods accounting for pathway topology reached higher accuracy than the gene set methods, however their sensitivity was lower. We conducted one of the first comprehensive comparative works on evaluating gene set against pathway topology-based enrichment methods. The topological methods showed better performance in the simulation scenarios with non-overlapping pathways, however, they were not conclusively better in the other scenarios. This suggests that simple gene set approach might be sufficient to detect an enriched pathway under realistic circumstances. Nevertheless, more extensive studies and further benchmark data are needed to systematically evaluate these methods and to assess what gain and cost pathway topology information introduces into enrichment analysis. Both

  14. Pathway analysis concepts for radiological impact assessment

    International Nuclear Information System (INIS)

    Moroney, J.R.

    1992-06-01

    The concepts underlying exposure pathways analysis are outlined with reference to the features of the two broad types of radionuclide transport models now in use - dynamic and steady-state - and the methods for constructing and developing them. By way of illustration, representative radiation doses are estimated for the four main exposure pathways likely to be involved in the land application of effluent water from Retention Pond 2 of Ranger Uranium Mines. These include: external irradiation by 226 Ra and natural uranium (Un at) in soil, ingestion of 226 Ra and Un at in food, inhalation of 222 Rn daughter products from 226 Rn in soil, and inhalation of 226 Ra and Un at in airborne dust resuspended from soil. Consideration has been given to local residents pursuing a traditional lifestyle on conclusion of the land application program. Because of the possible importance of the contribution from resuspended dust, currently available data are explored in refining the methodology for the pathway and developing a more appropriate model for it. 37 refs., 9 tabs., 6 figs

  15. Radical SAM, A Novel Protein Superfamily Linking Unresolved Steps in Familiar Biosynthetic Pathways with Radical Mechanisms: Functional Characterization Using New Analysis and Information Visualization Methods

    Energy Technology Data Exchange (ETDEWEB)

    Sofia, Heidi J.; Chen, Guang; Hetzler, Elizabeth G.; Reyes Spindola, Jorge F.; Miller, Nancy E.

    2001-03-01

    A large protein superfamily with over 500 members has been discovered and analyzed using powerful new bioinformatics and information visualization methods. Evidence exists that these proteins generate a 5?-deoxyadenosyl radical by reductive cleavage of S-adenosylmethionine (SAM) through an unusual Fe-S center. Radical SAM superfamily proteins function in DNA precursor, vitamin, cofactor, antibiotic, and herbicide biosynthesis in a collection of basic and familiar pathways. One of the members is interferon-inducible and is considered a candidate drug target for osteoporosis. The identification of this superfamily suggests that radical-based catalysis is important in a number of previously well-studied but unresolved biochemical pathways.

  16. Method for determining heterologous biosynthesis pathways

    KAUST Repository

    Gao, Xin; Kuwahara, Hiroyuki; Alazmi, Meshari Saud; Cui, Xuefeng

    2017-01-01

    suitable pathways for the endogenous metabolism of a host organism because the efficacy of heterologous biosynthesis is affected by competing endogenous pathways. The present invention is called MRE (Metabolic Route Explorer), and it was conceived

  17. Computational Chemical Synthesis Analysis and Pathway Design

    Directory of Open Access Journals (Sweden)

    Fan Feng

    2018-06-01

    Full Text Available With the idea of retrosynthetic analysis, which was raised in the 1960s, chemical synthesis analysis and pathway design have been transformed from a complex problem to a regular process of structural simplification. This review aims to summarize the developments of computer-assisted synthetic analysis and design in recent years, and how machine-learning algorithms contributed to them. LHASA system started the pioneering work of designing semi-empirical reaction modes in computers, with its following rule-based and network-searching work not only expanding the databases, but also building new approaches to indicating reaction rules. Programs like ARChem Route Designer replaced hand-coded reaction modes with automatically-extracted rules, and programs like Chematica changed traditional designing into network searching. Afterward, with the help of machine learning, two-step models which combine reaction rules and statistical methods became the main stream. Recently, fully data-driven learning methods using deep neural networks which even do not require any prior knowledge, were applied into this field. Up to now, however, these methods still cannot replace experienced human organic chemists due to their relatively low accuracies. Future new algorithms with the aid of powerful computational hardware will make this topic promising and with good prospects.

  18. Final report on the Pathway Analysis Task

    International Nuclear Information System (INIS)

    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

  19. Final report on the Pathway Analysis Task

    Energy Technology Data Exchange (ETDEWEB)

    Whicker, F.W.; Kirchner, T.B. [Colorado State Univ., Fort Collins, CO (United States)

    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.

  20. Pathway Processor 2.0: a web resource for pathway-based analysis of high-throughput data.

    Science.gov (United States)

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

    2013-07-15

    Pathway Processor 2.0 is a web application designed to analyze high-throughput datasets, including but not limited to microarray and next-generation sequencing, using a pathway centric logic. In addition to well-established methods such as the Fisher's test and impact analysis, Pathway Processor 2.0 offers innovative methods that convert gene expression into pathway expression, leading to the identification of differentially regulated pathways in a dataset of choice. Pathway Processor 2.0 is available as a web service at http://compbiotoolbox.fmach.it/pathwayProcessor/. Sample datasets to test the functionality can be used directly from the application. duccio.cavalieri@fmach.it Supplementary data are available at Bioinformatics online.

  1. Life cycle analysis of transportation fuel pathways

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2012-02-24

    The purpose of this work is to improve the understanding of the concept of life cycle analysis (LCA) of transportation fuels and some of its pertinent issues among non-technical people, senior managers, and policy makers. This work should provide some guidance to nations considering LCA-based policies and to people who are affected by existing policies or those being developed. While the concept of employing LCA to evaluate fuel options is simple and straightforward, the act of putting the concept into practice is complex and fraught with issues. Policy makers need to understand the limitations inherent in carrying out LCA work for transportation fuel systems. For many systems, even those that have been employed for a 100 years, there is a lack of sound data on the performance of those systems. Comparisons between systems should ideally be made using the same tool, so that differences caused by system boundaries, allocation processes, and temporal issues can be minimized (although probably not eliminated). Comparing the results for fuel pathway 1 from tool A to those of fuel system 2 from tool B introduces significant uncertainty into the results. There is also the question of the scale of system changes. LCA will give more reliable estimates when it is used to examine small changes in transportation fuel pathways than when used to estimate large scale changes that replace current pathways with completely new pathways. Some LCA tools have been developed recently primarily for regulatory purposes. These tools may deviate from ISO principles in order to facilitate simplicity and ease of use. In a regulatory environment, simplicity and ease of use are worthy objectives and in most cases there is nothing inherently wrong with this approach, particularly for assessing relative performance. However, the results of these tools should not be confused with, or compared to, the results that are obtained from a more complex and rigorous ISO compliant LCA. It should be

  2. An ensemble method to predict target genes and pathways in uveal melanoma

    Directory of Open Access Journals (Sweden)

    Wei Chao

    2018-04-01

    Full Text Available This work proposes to predict target genes and pathways for uveal melanoma (UM based on an ensemble method and pathway analyses. Methods: The ensemble method integrated a correlation method (Pearson correlation coefficient, PCC, a causal inference method (IDA and a regression method (Lasso utilizing the Borda count election method. Subsequently, to validate the performance of PIL method, comparisons between confirmed database and predicted miRNA targets were performed. Ultimately, pathway enrichment analysis was conducted on target genes in top 1000 miRNA-mRNA interactions to identify target pathways for UM patients. Results: Thirty eight of the predicted interactions were matched with the confirmed interactions, indicating that the ensemble method was a suitable and feasible approach to predict miRNA targets. We obtained 50 seed miRNA-mRNA interactions of UM patients and extracted target genes from these interactions, such as ASPG, BSDC1 and C4BP. The 601 target genes in top 1,000 miRNA-mRNA interactions were enriched in 12 target pathways, of which Phototransduction was the most significant one. Conclusion: The target genes and pathways might provide a new way to reveal the molecular mechanism of UM and give hand for target treatments and preventions of this malignant tumor.

  3. Analysis of Membrane Protein Topology in the Plant Secretory Pathway.

    Science.gov (United States)

    Guo, Jinya; Miao, Yansong; Cai, Yi

    2017-01-01

    Topology of membrane proteins provides important information for the understanding of protein function and intermolecular associations. Integrate membrane proteins are generally transported from endoplasmic reticulum (ER) to Golgi and downstream compartments in the plant secretory pathway. Here, we describe a simple method to study membrane protein topology along the plant secretory pathway by transiently coexpressing a fluorescent protein (XFP)-tagged membrane protein and an ER export inhibitor protein, ARF1 (T31N), in tobacco BY-2 protoplast. By fractionation, microsome isolation, and trypsin digestion, membrane protein topology could be easily detected by either direct confocal microscopy imaging or western-blot analysis using specific XFP antibodies. A similar strategy in determining membrane protein topology could be widely adopted and applied to protein analysis in a broad range of eukaryotic systems, including yeast cells and mammalian cells.

  4. Methods of assessing total doses integrated across pathways

    International Nuclear Information System (INIS)

    Grzechnik, M.; Camplin, W.; Clyne, F.; Allott, R.; Webbe-Wood, D.

    2006-01-01

    Calculated doses for comparison with limits resulting from discharges into the environment should be summed across all relevant pathways and food groups to ensure adequate protection. Current methodology for assessments used in the radioactivity in Food and the Environment (R.I.F.E.) reports separate doses from pathways related to liquid discharges of radioactivity to the environment from those due to gaseous releases. Surveys of local inhabitant food consumption and occupancy rates are conducted in the vicinity of nuclear sites. Information has been recorded in an integrated way, such that the data for each individual is recorded for all pathways of interest. These can include consumption of foods, such as fish, crustaceans, molluscs, fruit and vegetables, milk and meats. Occupancy times over beach sediments and time spent in close proximity to the site is also recorded for inclusion of external and inhalation radiation dose pathways. The integrated habits survey data may be combined with monitored environmental radionuclide concentrations to calculate total dose. The criteria for successful adoption of a method for this calculation were: Reproducibility can others easily use the approach and reassess doses? Rigour and realism how good is the match with reality?Transparency a measure of the ease with which others can understand how the calculations are performed and what they mean. Homogeneity is the group receiving the dose relatively homogeneous with respect to age, diet and those aspects that affect the dose received? Five methods of total dose calculation were compared and ranked according to their suitability. Each method was labelled (A to E) and given a short, relevant name for identification. The methods are described below; A) Individual doses to individuals are calculated and critical group selection is dependent on dose received. B) Individual Plus As in A, but consumption and occupancy rates for high dose is used to derive rates for application in

  5. A Pathway Based Classification Method for Analyzing Gene Expression for Alzheimer's Disease Diagnosis.

    Science.gov (United States)

    Voyle, Nicola; Keohane, Aoife; Newhouse, Stephen; Lunnon, Katie; Johnston, Caroline; Soininen, Hilkka; Kloszewska, Iwona; Mecocci, Patrizia; Tsolaki, Magda; Vellas, Bruno; Lovestone, Simon; Hodges, Angela; Kiddle, Steven; Dobson, Richard Jb

    2016-01-01

    Recent studies indicate that gene expression levels in blood may be able to differentiate subjects with Alzheimer's disease (AD) from normal elderly controls and mild cognitively impaired (MCI) subjects. However, there is limited replicability at the single marker level. A pathway-based interpretation of gene expression may prove more robust. This study aimed to investigate whether a case/control classification model built on pathway level data was more robust than a gene level model and may consequently perform better in test data. The study used two batches of gene expression data from the AddNeuroMed (ANM) and Dementia Case Registry (DCR) cohorts. Our study used Illumina Human HT-12 Expression BeadChips to collect gene expression from blood samples. Random forest modeling with recursive feature elimination was used to predict case/control status. Age and APOE ɛ4 status were used as covariates for all analysis. Gene and pathway level models performed similarly to each other and to a model based on demographic information only. Any potential increase in concordance from the novel pathway level approach used here has not lead to a greater predictive ability in these datasets. However, we have only tested one method for creating pathway level scores. Further, we have been able to benchmark pathways against genes in datasets that had been extensively harmonized. Further work should focus on the use of alternative methods for creating pathway level scores, in particular those that incorporate pathway topology, and the use of an endophenotype based approach.

  6. PathNet: a tool for pathway analysis using topological information

    Directory of Open Access Journals (Sweden)

    Dutta Bhaskar

    2012-09-01

    Full Text Available Abstract Background Identification of canonical pathways through enrichment of differentially expressed genes in a given pathway is a widely used method for interpreting gene lists generated from high-throughput experimental studies. However, most algorithms treat pathways as sets of genes, disregarding any inter- and intra-pathway connectivity information, and do not provide insights beyond identifying lists of pathways. Results We developed an algorithm (PathNet that utilizes the connectivity information in canonical pathway descriptions to help identify study-relevant pathways and characterize non-obvious dependencies and connections among pathways using gene expression data. PathNet considers both the differential expression of genes and their pathway neighbors to strengthen the evidence that a pathway is implicated in the biological conditions characterizing the experiment. As an adjunct to this analysis, PathNet uses the connectivity of the differentially expressed genes among all pathways to score pathway contextual associations and statistically identify biological relations among pathways. In this study, we used PathNet to identify biologically relevant results in two Alzheimer’s disease microarray datasets, and compared its performance with existing methods. Importantly, PathNet identified de-regulation of the ubiquitin-mediated proteolysis pathway as an important component in Alzheimer’s disease progression, despite the absence of this pathway in the standard enrichment analyses. Conclusions PathNet is a novel method for identifying enrichment and association between canonical pathways in the context of gene expression data. It takes into account topological information present in pathways to reveal biological information. PathNet is available as an R workspace image from http://www.bhsai.org/downloads/pathnet/.

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

    Directory of Open Access Journals (Sweden)

    Elisa Cirillo

    2017-11-01

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

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

    Science.gov (United States)

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

    2014-03-06

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

  9. The future use of pathway analysis in IAEA safeguards

    International Nuclear Information System (INIS)

    Budlong Sylvester, Kory; Pilat, J.; Murphy, Chantell

    2013-01-01

    Pathway analysis has the potential to play an important role in the development of a safeguards system that is more information driven, leveraging all the information available to the International Atomic Energy Agency (IAEA). Pathway analysis should be seen as an extension of traditional hypothesis testing used by the Agency in the past. The most attractive pathways based on the assessed capabilities of a given state can be identified and used in the development of state-level safeguards approaches. This ranking of pathways can be revised based on evidence of pathway use, or preparations for use, allowing limited safeguards resources to flow to the areas of highest concern. The possible uses of pathway analysis in the implementation of the IAEA's state-level concept are described along with implementation issues that will likely arise. The paper is followed by the slides of the presentation. (authors)

  10. Genetic variants in two pathways influence serum urate levels and gout risk: a systematic pathway analysis.

    Science.gov (United States)

    Dong, Zheng; Zhou, Jingru; Xu, Xia; Jiang, Shuai; Li, Yuan; Zhao, Dongbao; Yang, Chengde; Ma, Yanyun; Wang, Yi; He, Hongjun; Ji, Hengdong; Zhang, Juan; Yuan, Ziyu; Yang, Yajun; Wang, Xiaofeng; Pang, Yafei; Jin, Li; Zou, Hejian; Wang, Jiucun

    2018-03-01

    The aims of this study were to identify candidate pathways associated with serum urate and to explore the genetic effect of those pathways on the risk of gout. Pathway analysis of the loci identified in genome-wide association studies (GWASs) showed that the ion transmembrane transporter activity pathway (GO: 0015075) and the secondary active transmembrane transporter activity pathway (GO: 0015291) were both associated with serum urate concentrations, with P FDR values of 0.004 and 0.007, respectively. In a Chinese population of 4,332 individuals, the two pathways were also found to be associated with serum urate (P FDR  = 1.88E-05 and 3.44E-04, separately). In addition, these two pathways were further associated with the pathogenesis of gout (P FDR  = 1.08E-08 and 2.66E-03, respectively) in the Chinese population and a novel gout-associated gene, SLC17A2, was identified (OR = 0.83, P FDR  = 0.017). The mRNA expression of candidate genes also showed significant differences among different groups at pathway level. The present study identified two transmembrane transporter activity pathways (GO: 0015075 and GO: 0015291) were associations with serum urate concentrations and the risk of gout. SLC17A2 was identified as a novel gene that influenced the risk of gout.

  11. Safety assessment for deep underground disposal vault-pathways analysis

    International Nuclear Information System (INIS)

    Lyon, R.B.; Rosinger, E.L.J.

    1980-01-01

    The concept verification phase of the Canadian programme for the disposal of nuclear fuel waste encompasses a period of about three years before the start of site selection. During this time, the methodology for Environmental and Safety Assessment studies is being developed by focusing on a model site. Pathways analysis is an important component of these studies. It involves the prediction of the rate at which radionuclides might be released from a disposal vault and travel through the geosphere and biosphere to reach man. The pathways analysis studies cover three major topics: geosphere pathways analysis, biosphere pathways analysis and potentially-disruptive-phenomena analysis. Geosphere pathways analysis includes a total systems analysis, using the computer program GARD2, vault analysis, which considers container failure and waste leaching, hydrogeological modelling and geochemical modelling. Biosphere pathways analysis incorporates a compartmental modelling approach using the computer program RAMM, and a food chain analysis using the computer program FOOD II. Potentially-disruptive-phenomena analysis involves the estimation of the probability and consequences of events such as earthquakes which might reduce the effectiveness of the barriers preventing the release of radionuclides. The current stage of development of the required methodology and data is discussed in each of the three areas and preliminary results are presented. (author)

  12. ComPath: comparative enzyme analysis and annotation in pathway/subsystem contexts

    Directory of Open Access Journals (Sweden)

    Kim Sun

    2008-03-01

    Full Text Available Abstract Background Once a new genome is sequenced, one of the important questions is to determine the presence and absence of biological pathways. Analysis of biological pathways in a genome is a complicated task since a number of biological entities are involved in pathways and biological pathways in different organisms are not identical. Computational pathway identification and analysis thus involves a number of computational tools and databases and typically done in comparison with pathways in other organisms. This computational requirement is much beyond the capability of biologists, so information systems for reconstructing, annotating, and analyzing biological pathways are much needed. We introduce a new comparative pathway analysis workbench, ComPath, which integrates various resources and computational tools using an interactive spreadsheet-style web interface for reliable pathway analyses. Results ComPath allows users to compare biological pathways in multiple genomes using a spreadsheet style web interface where various sequence-based analysis can be performed either to compare enzymes (e.g. sequence clustering and pathways (e.g. pathway hole identification, to search a genome for de novo prediction of enzymes, or to annotate a genome in comparison with reference genomes of choice. To fill in pathway holes or make de novo enzyme predictions, multiple computational methods such as FASTA, Whole-HMM, CSR-HMM (a method of our own introduced in this paper, and PDB-domain search are integrated in ComPath. Our experiments show that FASTA and CSR-HMM search methods generally outperform Whole-HMM and PDB-domain search methods in terms of sensitivity, but FASTA search performs poorly in terms of specificity, detecting more false positive as E-value cutoff increases. Overall, CSR-HMM search method performs best in terms of both sensitivity and specificity. Gene neighborhood and pathway neighborhood (global network visualization tools can be used

  13. A Novel Method to Identify Differential Pathways in Hippocampus Alzheimer's Disease.

    Science.gov (United States)

    Liu, Chun-Han; Liu, Lian

    2017-05-08

    BACKGROUND Alzheimer's disease (AD) is the most common type of dementia. The objective of this paper is to propose a novel method to identify differential pathways in hippocampus AD. MATERIAL AND METHODS We proposed a combined method by merging existed methods. Firstly, pathways were identified by four known methods (DAVID, the neaGUI package, the pathway-based co-expressed method, and the pathway network approach), and differential pathways were evaluated through setting weight thresholds. Subsequently, we combined all pathways by a rank-based algorithm and called the method the combined method. Finally, common differential pathways across two or more of five methods were selected. RESULTS Pathways obtained from different methods were also different. The combined method obtained 1639 pathways and 596 differential pathways, which included all pathways gained from the four existing methods; hence, the novel method solved the problem of inconsistent results. Besides, a total of 13 common pathways were identified, such as metabolism, immune system, and cell cycle. CONCLUSIONS We have proposed a novel method by combining four existing methods based on a rank product algorithm, and identified 13 significant differential pathways based on it. These differential pathways might provide insight into treatment and diagnosis of hippocampus AD.

  14. The surface analysis methods

    International Nuclear Information System (INIS)

    Deville, J.P.

    1998-01-01

    Nowadays, there are a lot of surfaces analysis methods, each having its specificity, its qualities, its constraints (for instance vacuum) and its limits. Expensive in time and in investment, these methods have to be used deliberately. This article appeals to non specialists. It gives some elements of choice according to the studied information, the sensitivity, the use constraints or the answer to a precise question. After having recalled the fundamental principles which govern these analysis methods, based on the interaction between radiations (ultraviolet, X) or particles (ions, electrons) with matter, two methods will be more particularly described: the Auger electron spectroscopy (AES) and x-rays photoemission spectroscopy (ESCA or XPS). Indeed, they are the most widespread methods in laboratories, the easier for use and probably the most productive for the analysis of surface of industrial materials or samples submitted to treatments in aggressive media. (O.M.)

  15. Methods of Multivariate Analysis

    CERN Document Server

    Rencher, Alvin C

    2012-01-01

    Praise for the Second Edition "This book is a systematic, well-written, well-organized text on multivariate analysis packed with intuition and insight . . . There is much practical wisdom in this book that is hard to find elsewhere."-IIE Transactions Filled with new and timely content, Methods of Multivariate Analysis, Third Edition provides examples and exercises based on more than sixty real data sets from a wide variety of scientific fields. It takes a "methods" approach to the subject, placing an emphasis on how students and practitioners can employ multivariate analysis in real-life sit

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

    DEFF Research Database (Denmark)

    Weber, Tilmann

    2014-01-01

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

  17. Integrating computational methods to retrofit enzymes to synthetic pathways.

    Science.gov (United States)

    Brunk, Elizabeth; Neri, Marilisa; Tavernelli, Ivano; Hatzimanikatis, Vassily; Rothlisberger, Ursula

    2012-02-01

    Microbial production of desired compounds provides an efficient framework for the development of renewable energy resources. To be competitive to traditional chemistry, one requirement is to utilize the full capacity of the microorganism to produce target compounds with high yields and turnover rates. We use integrated computational methods to generate and quantify the performance of novel biosynthetic routes that contain highly optimized catalysts. Engineering a novel reaction pathway entails addressing feasibility on multiple levels, which involves handling the complexity of large-scale biochemical networks while respecting the critical chemical phenomena at the atomistic scale. To pursue this multi-layer challenge, our strategy merges knowledge-based metabolic engineering methods with computational chemistry methods. By bridging multiple disciplines, we provide an integral computational framework that could accelerate the discovery and implementation of novel biosynthetic production routes. Using this approach, we have identified and optimized a novel biosynthetic route for the production of 3HP from pyruvate. Copyright © 2011 Wiley Periodicals, Inc.

  18. The Ability of Different Imputation Methods to Preserve the Significant Genes and Pathways in Cancer

    Directory of Open Access Journals (Sweden)

    Rosa Aghdam

    2017-12-01

    Full Text Available Deciphering important genes and pathways from incomplete gene expression data could facilitate a better understanding of cancer. Different imputation methods can be applied to estimate the missing values. In our study, we evaluated various imputation methods for their performance in preserving significant genes and pathways. In the first step, 5% genes are considered in random for two types of ignorable and non-ignorable missingness mechanisms with various missing rates. Next, 10 well-known imputation methods were applied to the complete datasets. The significance analysis of microarrays (SAM method was applied to detect the significant genes in rectal and lung cancers to showcase the utility of imputation approaches in preserving significant genes. To determine the impact of different imputation methods on the identification of important genes, the chi-squared test was used to compare the proportions of overlaps between significant genes detected from original data and those detected from the imputed datasets. Additionally, the significant genes are tested for their enrichment in important pathways, using the ConsensusPathDB. Our results showed that almost all the significant genes and pathways of the original dataset can be detected in all imputed datasets, indicating that there is no significant difference in the performance of various imputation methods tested. The source code and selected datasets are available on http://profiles.bs.ipm.ir/softwares/imputation_methods/.

  19. The Ability of Different Imputation Methods to Preserve the Significant Genes and Pathways in Cancer.

    Science.gov (United States)

    Aghdam, Rosa; Baghfalaki, Taban; Khosravi, Pegah; Saberi Ansari, Elnaz

    2017-12-01

    Deciphering important genes and pathways from incomplete gene expression data could facilitate a better understanding of cancer. Different imputation methods can be applied to estimate the missing values. In our study, we evaluated various imputation methods for their performance in preserving significant genes and pathways. In the first step, 5% genes are considered in random for two types of ignorable and non-ignorable missingness mechanisms with various missing rates. Next, 10 well-known imputation methods were applied to the complete datasets. The significance analysis of microarrays (SAM) method was applied to detect the significant genes in rectal and lung cancers to showcase the utility of imputation approaches in preserving significant genes. To determine the impact of different imputation methods on the identification of important genes, the chi-squared test was used to compare the proportions of overlaps between significant genes detected from original data and those detected from the imputed datasets. Additionally, the significant genes are tested for their enrichment in important pathways, using the ConsensusPathDB. Our results showed that almost all the significant genes and pathways of the original dataset can be detected in all imputed datasets, indicating that there is no significant difference in the performance of various imputation methods tested. The source code and selected datasets are available on http://profiles.bs.ipm.ir/softwares/imputation_methods/. Copyright © 2017. Production and hosting by Elsevier B.V.

  20. A novel bi-level meta-analysis approach: applied to biological pathway analysis.

    Science.gov (United States)

    Nguyen, Tin; Tagett, Rebecca; Donato, Michele; Mitrea, Cristina; Draghici, Sorin

    2016-02-01

    The accumulation of high-throughput data in public repositories creates a pressing need for integrative analysis of multiple datasets from independent experiments. However, study heterogeneity, study bias, outliers and the lack of power of available methods present real challenge in integrating genomic data. One practical drawback of many P-value-based meta-analysis methods, including Fisher's, Stouffer's, minP and maxP, is that they are sensitive to outliers. Another drawback is that, because they perform just one statistical test for each individual experiment, they may not fully exploit the potentially large number of samples within each study. We propose a novel bi-level meta-analysis approach that employs the additive method and the Central Limit Theorem within each individual experiment and also across multiple experiments. We prove that the bi-level framework is robust against bias, less sensitive to outliers than other methods, and more sensitive to small changes in signal. For comparative analysis, we demonstrate that the intra-experiment analysis has more power than the equivalent statistical test performed on a single large experiment. For pathway analysis, we compare the proposed framework versus classical meta-analysis approaches (Fisher's, Stouffer's and the additive method) as well as against a dedicated pathway meta-analysis package (MetaPath), using 1252 samples from 21 datasets related to three human diseases, acute myeloid leukemia (9 datasets), type II diabetes (5 datasets) and Alzheimer's disease (7 datasets). Our framework outperforms its competitors to correctly identify pathways relevant to the phenotypes. The framework is sufficiently general to be applied to any type of statistical meta-analysis. The R scripts are available on demand from the authors. sorin@wayne.edu Supplementary data are available at Bioinformatics online. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e

  1. minepath.org: a free interactive pathway analysis web server.

    Science.gov (United States)

    Koumakis, Lefteris; Roussos, Panos; Potamias, George

    2017-07-03

    ( www.minepath.org ) is a web-based platform that elaborates on, and radically extends the identification of differentially expressed sub-paths in molecular pathways. Besides the network topology, the underlying MinePath algorithmic processes exploit exact gene-gene molecular relationships (e.g. activation, inhibition) and are able to identify differentially expressed pathway parts. Each pathway is decomposed into all its constituent sub-paths, which in turn are matched with corresponding gene expression profiles. The highly ranked, and phenotype inclined sub-paths are kept. Apart from the pathway analysis algorithm, the fundamental innovation of the MinePath web-server concerns its advanced visualization and interactive capabilities. To our knowledge, this is the first pathway analysis server that introduces and offers visualization of the underlying and active pathway regulatory mechanisms instead of genes. Other features include live interaction, immediate visualization of functional sub-paths per phenotype and dynamic linked annotations for the engaged genes and molecular relations. The user can download not only the results but also the corresponding web viewer framework of the performed analysis. This feature provides the flexibility to immediately publish results without publishing source/expression data, and get all the functionality of a web based pathway analysis viewer. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

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

    DEFF Research Database (Denmark)

    Jørgensen, Peter Stanley; Ebbehøj, Søren Lyng; Hauch, Anne

    2015-01-01

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

  3. Metabolomics Study of Resina Draconis on Myocardial Ischemia Rats Using Ultraperformance Liquid Chromatography/Quadrupole Time-of-Flight Mass Spectrometry Combined with Pattern Recognition Methods and Metabolic Pathway Analysis

    Directory of Open Access Journals (Sweden)

    Yunpeng Qi

    2013-01-01

    Full Text Available Resina draconis (bright red resin isolated from Dracaena cochinchinensis, RD has been clinically used for treatment of myocardial ischemia (MI for many years. However, the mechanisms of its pharmacological action on MI are still poorly understood. This study aimed to characterize the plasma metabolic profiles of MI and investigate the mechanisms of RD on MI using ultraperformance liquid chromatography/quadrupole time-of-flight mass spectrometry-based metabolomics combined with pattern recognition methods and metabolic pathway analysis. Twenty metabolite markers characterizing metabolic profile of MI were revealed, which were mainly involved in aminoacyl-tRNA biosynthesis, phenylalanine, tyrosine, and tryptophan biosynthesis, vascular smooth muscle contraction, sphingolipid metabolism, and so forth. After RD treatment, however, levels of seven MI metabolite markers, including phytosphingosine, sphinganine, acetylcarnitine, cGMP, cAMP, L-tyrosine, and L-valine, were turned over, indicating that RD is likely to alleviate MI through regulating the disturbed vascular smooth muscle contraction, sphingolipid metabolism, phenylalanine metabolism, and BCAA metabolism. To our best knowledge, this is the first comprehensive study to investigate the mechanisms of RD for treating MI, from a metabolomics point of view. Our findings are very valuable to gain a better understanding of MI metabolic profiles and provide novel insights for exploring the mechanisms of RD on MI.

  4. Methods for RNA Analysis

    DEFF Research Database (Denmark)

    Olivarius, Signe

    of the transcriptome, 5’ end capture of RNA is combined with next-generation sequencing for high-throughput quantitative assessment of transcription start sites by two different methods. The methods presented here allow for functional investigation of coding as well as noncoding RNA and contribute to future...... RNAs rely on interactions with proteins, the establishment of protein-binding profiles is essential for the characterization of RNAs. Aiming to facilitate RNA analysis, this thesis introduces proteomics- as well as transcriptomics-based methods for the functional characterization of RNA. First, RNA...

  5. Analysis of numerical methods

    CERN Document Server

    Isaacson, Eugene

    1994-01-01

    This excellent text for advanced undergraduates and graduate students covers norms, numerical solution of linear systems and matrix factoring, iterative solutions of nonlinear equations, eigenvalues and eigenvectors, polynomial approximation, and other topics. It offers a careful analysis and stresses techniques for developing new methods, plus many examples and problems. 1966 edition.

  6. Integrated Genomic Analysis of the Ubiquitin Pathway across Cancer Types

    Directory of Open Access Journals (Sweden)

    Zhongqi Ge

    2018-04-01

    Full Text Available Summary: Protein ubiquitination is a dynamic and reversible process of adding single ubiquitin molecules or various ubiquitin chains to target proteins. Here, using multidimensional omic data of 9,125 tumor samples across 33 cancer types from The Cancer Genome Atlas, we perform comprehensive molecular characterization of 929 ubiquitin-related genes and 95 deubiquitinase genes. Among them, we systematically identify top somatic driver candidates, including mutated FBXW7 with cancer-type-specific patterns and amplified MDM2 showing a mutually exclusive pattern with BRAF mutations. Ubiquitin pathway genes tend to be upregulated in cancer mediated by diverse mechanisms. By integrating pan-cancer multiomic data, we identify a group of tumor samples that exhibit worse prognosis. These samples are consistently associated with the upregulation of cell-cycle and DNA repair pathways, characterized by mutated TP53, MYC/TERT amplification, and APC/PTEN deletion. Our analysis highlights the importance of the ubiquitin pathway in cancer development and lays a foundation for developing relevant therapeutic strategies. : Ge et al. analyze a cohort of 9,125 TCGA samples across 33 cancer types to provide a comprehensive characterization of the ubiquitin pathway. They detect somatic driver candidates in the ubiquitin pathway and identify a cluster of patients with poor survival, highlighting the importance of this pathway in cancer development. Keywords: ubiquitin pathway, pan-cancer analysis, The Cancer Genome Atlas, tumor subtype, cancer prognosis, therapeutic targets, biomarker, FBXW7

  7. Final Report: Hydrogen Production Pathways Cost Analysis (2013 – 2016)

    Energy Technology Data Exchange (ETDEWEB)

    James, Brian David [Strategic Analysis Inc., Arlington, VA (United States); DeSantis, Daniel Allan [Strategic Analysis Inc., Arlington, VA (United States); Saur, Genevieve [National Renewable Energy Lab. (NREL), Golden, CO (United States)

    2016-09-30

    This report summarizes work conducted under a three year Department of Energy (DOE) funded project to Strategic Analysis, Inc. (SA) to analyze multiple hydrogen (H2) production technologies and project their corresponding levelized production cost of H2. The analysis was conducted using the H2A Hydrogen Analysis Tool developed by the DOE and National Renewable Energy Laboratory (NREL). The project was led by SA but conducted in close collaboration with the NREL and Argonne National Laboratory (ANL). In-depth techno-economic analysis (TEA) of five different H2 production methods was conducted. These TEAs developed projections for capital costs, fuel/feedstock usage, energy usage, indirect capital costs, land usage, labor requirements, and other parameters, for each H2 production pathway, and use the resulting cost and system parameters as inputs into the H2A discounted cash flow model to project the production cost of H2 ($/kgH2). Five technologies were analyzed as part of the project and are summarized in this report: Proton Exchange Membrane technology (PEM), High temperature solid oxide electrolysis cell technology (SOEC), Dark fermentation of biomass for H2 production, H2 production via Monolithic Piston-Type Reactors with rapid swing reforming and regeneration reactions, and Reformer-Electrolyzer-Purifier (REP) technology developed by Fuel Cell Energy, Inc. (FCE).

  8. Methods for Risk Analysis

    International Nuclear Information System (INIS)

    Alverbro, Karin

    2010-01-01

    Many decision-making situations today affect humans and the environment. In practice, many such decisions are made without an overall view and prioritise one or other of the two areas. Now and then these two areas of regulation come into conflict, e.g. the best alternative as regards environmental considerations is not always the best from a human safety perspective and vice versa. This report was prepared within a major project with the aim of developing a framework in which both the environmental aspects and the human safety aspects are integrated, and decisions can be made taking both fields into consideration. The safety risks have to be analysed in order to be successfully avoided and one way of doing this is to use different kinds of risk analysis methods. There is an abundance of existing methods to choose from and new methods are constantly being developed. This report describes some of the risk analysis methods currently available for analysing safety and examines the relationships between them. The focus here is mainly on human safety aspects

  9. Modelling and Analysis of Biochemical Signalling Pathway Cross-talk

    Directory of Open Access Journals (Sweden)

    Robin Donaldson

    2010-02-01

    Full Text Available Signalling pathways are abstractions that help life scientists structure the coordination of cellular activity. Cross-talk between pathways accounts for many of the complex behaviours exhibited by signalling pathways and is often critical in producing the correct signal-response relationship. Formal models of signalling pathways and cross-talk in particular can aid understanding and drive experimentation. We define an approach to modelling based on the concept that a pathway is the (synchronising parallel composition of instances of generic modules (with internal and external labels. Pathways are then composed by (synchronising parallel composition and renaming; different types of cross-talk result from different combinations of synchronisation and renaming. We define a number of generic modules in PRISM and five types of cross-talk: signal flow, substrate availability, receptor function, gene expression and intracellular communication. We show that Continuous Stochastic Logic properties can both detect and distinguish the types of cross-talk. The approach is illustrated with small examples and an analysis of the cross-talk between the TGF-b/BMP, WNT and MAPK pathways.

  10. Pathway-based outlier method reveals heterogeneous genomic structure of autism in blood transcriptome.

    Science.gov (United States)

    Campbell, Malcolm G; Kohane, Isaac S; Kong, Sek Won

    2013-09-24

    Decades of research strongly suggest that the genetic etiology of autism spectrum disorders (ASDs) is heterogeneous. However, most published studies focus on group differences between cases and controls. In contrast, we hypothesized that the heterogeneity of the disorder could be characterized by identifying pathways for which individuals are outliers rather than pathways representative of shared group differences of the ASD diagnosis. Two previously published blood gene expression data sets--the Translational Genetics Research Institute (TGen) dataset (70 cases and 60 unrelated controls) and the Simons Simplex Consortium (Simons) dataset (221 probands and 191 unaffected family members)--were analyzed. All individuals of each dataset were projected to biological pathways, and each sample's Mahalanobis distance from a pooled centroid was calculated to compare the number of case and control outliers for each pathway. Analysis of a set of blood gene expression profiles from 70 ASD and 60 unrelated controls revealed three pathways whose outliers were significantly overrepresented in the ASD cases: neuron development including axonogenesis and neurite development (29% of ASD, 3% of control), nitric oxide signaling (29%, 3%), and skeletal development (27%, 3%). Overall, 50% of cases and 8% of controls were outliers in one of these three pathways, which could not be identified using group comparison or gene-level outlier methods. In an independently collected data set consisting of 221 ASD and 191 unaffected family members, outliers in the neurogenesis pathway were heavily biased towards cases (20.8% of ASD, 12.0% of control). Interestingly, neurogenesis outliers were more common among unaffected family members (Simons) than unrelated controls (TGen), but the statistical significance of this effect was marginal (Chi squared P < 0.09). Unlike group difference approaches, our analysis identified the samples within the case and control groups that manifested each expression

  11. Application of the critical pathway and integrated case teaching method to nursing orientation.

    Science.gov (United States)

    Goodman, D

    1997-01-01

    Nursing staff development programs must be responsive to current changes in healthcare. New nursing staff must be prepared to manage continuous change and to function competently in clinical practice. The orientation pathway, based on a case management model, is used as a structure for the orientation phase of staff development. The integrated case is incorporated as a teaching strategy in orientation. The integrated case method is based on discussion and analysis of patient situations with emphasis on role modeling and integration of theory and skill. The orientation pathway and integrated case teaching method provide a useful framework for orientation of new staff. Educators, preceptors and orientees find the structure provided by the orientation pathway very useful. Orientation that is developed, implemented and evaluated based on a case management model with the use of an orientation pathway and incorporation of an integrated case teaching method provides a standardized structure for orientation of new staff. This approach is designed for the adult learner, promotes conceptual reasoning, and encourages the social and contextual basis for continued learning.

  12. Method of signal analysis

    International Nuclear Information System (INIS)

    Berthomier, Charles

    1975-01-01

    A method capable of handling the amplitude and the frequency time laws of a certain kind of geophysical signals is described here. This method is based upon the analytical signal idea of Gabor and Ville, which is constructed either in the time domain by adding an imaginary part to the real signal (in-quadrature signal), or in the frequency domain by suppressing negative frequency components. The instantaneous frequency of the initial signal is then defined as the time derivative of the phase of the analytical signal, and his amplitude, or envelope, as the modulus of this complex signal. The method is applied to three types of magnetospheric signals: chorus, whistlers and pearls. The results obtained by analog and numerical calculations are compared to results obtained by classical systems using filters, i.e. based upon a different definition of the concept of frequency. The precision with which the frequency-time laws are determined leads then to the examination of the principle of the method and to a definition of instantaneous power density spectrum attached to the signal, and to the first consequences of this definition. In this way, a two-dimensional representation of the signal is introduced which is less deformed by the analysis system properties than the usual representation, and which moreover has the advantage of being obtainable practically in real time [fr

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

    Directory of Open Access Journals (Sweden)

    Bai Chunyan

    2009-09-01

    Full Text Available Abstract 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.

  14. Methods for geochemical analysis

    Science.gov (United States)

    Baedecker, Philip A.

    1987-01-01

    The laboratories for analytical chemistry within the Geologic Division of the U.S. Geological Survey are administered by the Office of Mineral Resources. The laboratory analysts provide analytical support to those programs of the Geologic Division that require chemical information and conduct basic research in analytical and geochemical areas vital to the furtherance of Division program goals. Laboratories for research and geochemical analysis are maintained at the three major centers in Reston, Virginia, Denver, Colorado, and Menlo Park, California. The Division has an expertise in a broad spectrum of analytical techniques, and the analytical research is designed to advance the state of the art of existing techniques and to develop new methods of analysis in response to special problems in geochemical analysis. The geochemical research and analytical results are applied to the solution of fundamental geochemical problems relating to the origin of mineral deposits and fossil fuels, as well as to studies relating to the distribution of elements in varied geologic systems, the mechanisms by which they are transported, and their impact on the environment.

  15. COMPUTER METHODS OF GENETIC ANALYSIS.

    Directory of Open Access Journals (Sweden)

    A. L. Osipov

    2017-02-01

    Full Text Available The basic statistical methods used in conducting the genetic analysis of human traits. We studied by segregation analysis, linkage analysis and allelic associations. Developed software for the implementation of these methods support.

  16. Atmospheric Pathway Screening Analysis for Saltstone Disposal Facility Vault 4

    International Nuclear Information System (INIS)

    COOK, JAMES

    2004-01-01

    A sequential screening process using a methodology developed by the National Council on Radiation Protection and Measurements, professional judgment and process knowledge has been used to produce a list of radionuclides requiring detailed analysis to derive disposal limits for the Saltstone Disposal Facility based on the atmospheric pathway

  17. Analysis of Chlorogenic Acid Oxidation Pathway in Simulated ...

    African Journals Online (AJOL)

    Purpose: To investigate the pathways involved in the oxidation of chlorogenic acid (CA) and phenol metabolism in honeysuckle buds. Methods: A model that mimics CA oxidation by honeysuckle polyphenol oxidase (PPO) by controlling the reaction temperature or reaction duration was employed, and the resulting products ...

  18. Analysis of Geothermal Pathway in the Metamorphic Area, Northeastern Taiwan

    Science.gov (United States)

    Wang, C.; Wu, M. Y.; Song, S. R.; Lo, W.

    2016-12-01

    A quantitative measure by play fairway analysis in geothermal energy development is an important tool that can present the probability map of potential resources through the uncertainty studies in geology for early phase decision making purpose in the related industries. While source, pathway, and fluid are the three main geologic factors in traditional geothermal systems, identifying the heat paths is critical to reduce drilling cost. Taiwan is in East Asia and the western edge of Pacific Ocean, locating on the convergent boundary of Eurasian Plate and Philippine Sea Plate with many earthquake activities. This study chooses a metamorphic area in the western corner of Yi-Lan plain in northeastern Taiwan with high geothermal potential and several existing exploration sites. Having high subsurface temperature gradient from the mountain belts, and plenty hydrologic systems through thousands of millimeters annual precipitation that would bring up heats closer to the surface, current geothermal conceptual model indicates the importance of pathway distribution which affects the possible concentration of extractable heat location. The study conducts surface lineation analysis using analytic hierarchy process to determine weights among various fracture types for their roles in geothermal pathways, based on the information of remote sensing data, published geologic maps and field work measurements, to produce regional fracture distribution probability map. The results display how the spatial distribution of pathways through various fractures could affect geothermal systems, identify the geothermal plays using statistical data analysis, and compare against the existing drilling data.

  19. A novel approach to select differential pathways associated with hypertrophic cardiomyopathy based on gene co‑expression analysis.

    Science.gov (United States)

    Chen, Xiao-Min; Feng, Ming-Jun; Shen, Cai-Jie; He, Bin; Du, Xian-Feng; Yu, Yi-Bo; Liu, Jing; Chu, Hui-Min

    2017-07-01

    The present study was designed to develop a novel method for identifying significant pathways associated with human hypertrophic cardiomyopathy (HCM), based on gene co‑expression analysis. The microarray dataset associated with HCM (E‑GEOD‑36961) was obtained from the European Molecular Biology Laboratory‑European Bioinformatics Institute database. Informative pathways were selected based on the Reactome pathway database and screening treatments. An empirical Bayes method was utilized to construct co‑expression networks for informative pathways, and a weight value was assigned to each pathway. Differential pathways were extracted based on weight threshold, which was calculated using a random model. In order to assess whether the co‑expression method was feasible, it was compared with traditional pathway enrichment analysis of differentially expressed genes, which were identified using the significance analysis of microarrays package. A total of 1,074 informative pathways were screened out for subsequent investigations and their weight values were also obtained. According to the threshold of weight value of 0.01057, 447 differential pathways, including folding of actin by chaperonin containing T‑complex protein 1 (CCT)/T‑complex protein 1 ring complex (TRiC), purine ribonucleoside monophosphate biosynthesis and ubiquinol biosynthesis, were obtained. Compared with traditional pathway enrichment analysis, the number of pathways obtained from the co‑expression approach was increased. The results of the present study demonstrated that this method may be useful to predict marker pathways for HCM. The pathways of folding of actin by CCT/TRiC and purine ribonucleoside monophosphate biosynthesis may provide evidence of the underlying molecular mechanisms of HCM, and offer novel therapeutic directions for HCM.

  20. Effects of clinical pathways in the joint replacement: a meta-analysis

    Directory of Open Access Journals (Sweden)

    Faggiano F

    2009-07-01

    Full Text Available Abstract Background A meta-analysis was performed to evaluate the use of clinical pathways for hip and knee joint replacements when compared with standard medical care. The impact of clinical pathways was evaluated assessing the major outcomes of in-hospital hip and knee joint replacement processes: postoperative complications, number of patients discharged at home, length of in-hospital stay and direct costs. Methods Medline, Cinahl, Embase and the Cochrane Central Register of Controlled Trials were searched. The search was performed from 1975 to 2007. Each study was assessed independently by two reviewers. The assessment of methodological quality of the included studies was based on the Jadad methodological approach and on the New Castle Ottawa Scale. Data analysis abided by the guidelines set out by The Cochrane Collaboration regarding statistical methods. Meta-analyses were performed using RevMan software, version 4.2. Results Twenty-two studies met the study inclusion criteria and were included in the meta-analysis for a total sample of 6,316 patients. The aggregate overall results showed significantly fewer patients suffering postoperative complications in the clinical pathways group when compared with the standard care group. A shorter length of stay in the clinical pathway group was also observed and lower costs during hospital stay were associated with the use of the clinical pathways. No significant differences were found in the rates of discharge to home. Conclusion The results of this meta-analysis show that clinical pathways can significantly improve the quality of care even if it is not possible to conclude that the implementation of clinical pathways is a cost-effective process, because none of the included studies analysed the cost of the development and implementation of the pathways. Based on the results we assume that pathways have impact on the organisation of care if the care process is structured in a standardised way

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

    Directory of Open Access Journals (Sweden)

    Fiehn Oliver

    2006-11-01

    Full Text Available Abstract 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 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 of patient at high risk for this disease; we provide pilot data for such a urinary bioassay. Furthermore, we demonstrate how the knowledge of networks, processes, and pathways altered in kidney cancer may be used to influence the choice of optimal therapy.

  2. Similar judgment method of brain neural pathway using DT-MRI

    International Nuclear Information System (INIS)

    Watashiba, Yasuhiro; Sakamoto, Naohisa; Sakai, Koji; Koyamada, Koji; Kanazawa, Masanori; Doi, Akio

    2008-01-01

    Nowadays, the visualization of brain neural pathway extracted by the tractography technology is thought as a useful effective tool for the detection of involved area and the analysis of sick cause by comparison of difference of normal and patient's nerve fiber configurations and for the support of the surgery planning and the forecast of progress after an operation. So far, for the observation of the brain neural pathway, the method of the user's subjectively judging the 3D shape of them displayed in the image has been used. However, in this kind of subjective observation, verification of the propriety for the diagnostic result is difficult, in addition it cannot obtain sufficient reliability. Therefore, we think that the system to compare the shape based on a quantitative evaluation is necessary. To resolve this problem, we propose the system that enables the shape of the brain neural pathway extracted by the tractography technology to be compared quantitatively. The proposed system realized to calculate similarity between two neural pathways, and to display the difference area according to the similarity. (author)

  3. Integration of multiple networks and pathways identifies cancer driver genes in pan-cancer analysis.

    Science.gov (United States)

    Cava, Claudia; Bertoli, Gloria; Colaprico, Antonio; Olsen, Catharina; Bontempi, Gianluca; Castiglioni, Isabella

    2018-01-06

    Modern high-throughput genomic technologies represent a comprehensive hallmark of molecular changes in pan-cancer studies. Although different cancer gene signatures have been revealed, the mechanism of tumourigenesis has yet to be completely understood. Pathways and networks are important tools to explain the role of genes in functional genomic studies. However, few methods consider the functional non-equal roles of genes in pathways and the complex gene-gene interactions in a network. We present a novel method in pan-cancer analysis that identifies de-regulated genes with a functional role by integrating pathway and network data. A pan-cancer analysis of 7158 tumour/normal samples from 16 cancer types identified 895 genes with a central role in pathways and de-regulated in cancer. Comparing our approach with 15 current tools that identify cancer driver genes, we found that 35.6% of the 895 genes identified by our method have been found as cancer driver genes with at least 2/15 tools. Finally, we applied a machine learning algorithm on 16 independent GEO cancer datasets to validate the diagnostic role of cancer driver genes for each cancer. We obtained a list of the top-ten cancer driver genes for each cancer considered in this study. Our analysis 1) confirmed that there are several known cancer driver genes in common among different types of cancer, 2) highlighted that cancer driver genes are able to regulate crucial pathways.

  4. Constraint-based modeling and kinetic analysis of the Smad dependent TGF-beta signaling pathway.

    Directory of Open Access Journals (Sweden)

    Zhike Zi

    Full Text Available BACKGROUND: Investigation of dynamics and regulation of the TGF-beta signaling pathway is central to the understanding of complex cellular processes such as growth, apoptosis, and differentiation. In this study, we aim at using systems biology approach to provide dynamic analysis on this pathway. METHODOLOGY/PRINCIPAL FINDINGS: We proposed a constraint-based modeling method to build a comprehensive mathematical model for the Smad dependent TGF-beta signaling pathway by fitting the experimental data and incorporating the qualitative constraints from the experimental analysis. The performance of the model generated by constraint-based modeling method is significantly improved compared to the model obtained by only fitting the quantitative data. The model agrees well with the experimental analysis of TGF-beta pathway, such as the time course of nuclear phosphorylated Smad, the subcellular location of Smad and signal response of Smad phosphorylation to different doses of TGF-beta. CONCLUSIONS/SIGNIFICANCE: The simulation results indicate that the signal response to TGF-beta is regulated by the balance between clathrin dependent endocytosis and non-clathrin mediated endocytosis. This model is useful to be built upon as new precise experimental data are emerging. The constraint-based modeling method can also be applied to quantitative modeling of other signaling pathways.

  5. Pathway-Based Kernel Boosting for the Analysis of Genome-Wide Association Studies

    Science.gov (United States)

    Manitz, Juliane; Burger, Patricia; Amos, Christopher I.; Chang-Claude, Jenny; Wichmann, Heinz-Erich; Kneib, Thomas; Bickeböller, Heike

    2017-01-01

    The analysis of genome-wide association studies (GWAS) benefits from the investigation of biologically meaningful gene sets, such as gene-interaction networks (pathways). We propose an extension to a successful kernel-based pathway analysis approach by integrating kernel functions into a powerful algorithmic framework for variable selection, to enable investigation of multiple pathways simultaneously. We employ genetic similarity kernels from the logistic kernel machine test (LKMT) as base-learners in a boosting algorithm. A model to explain case-control status is created iteratively by selecting pathways that improve its prediction ability. We evaluated our method in simulation studies adopting 50 pathways for different sample sizes and genetic effect strengths. Additionally, we included an exemplary application of kernel boosting to a rheumatoid arthritis and a lung cancer dataset. Simulations indicate that kernel boosting outperforms the LKMT in certain genetic scenarios. Applications to GWAS data on rheumatoid arthritis and lung cancer resulted in sparse models which were based on pathways interpretable in a clinical sense. Kernel boosting is highly flexible in terms of considered variables and overcomes the problem of multiple testing. Additionally, it enables the prediction of clinical outcomes. Thus, kernel boosting constitutes a new, powerful tool in the analysis of GWAS data and towards the understanding of biological processes involved in disease susceptibility. PMID:28785300

  6. Pathway-Based Kernel Boosting for the Analysis of Genome-Wide Association Studies.

    Science.gov (United States)

    Friedrichs, Stefanie; Manitz, Juliane; Burger, Patricia; Amos, Christopher I; Risch, Angela; Chang-Claude, Jenny; Wichmann, Heinz-Erich; Kneib, Thomas; Bickeböller, Heike; Hofner, Benjamin

    2017-01-01

    The analysis of genome-wide association studies (GWAS) benefits from the investigation of biologically meaningful gene sets, such as gene-interaction networks (pathways). We propose an extension to a successful kernel-based pathway analysis approach by integrating kernel functions into a powerful algorithmic framework for variable selection, to enable investigation of multiple pathways simultaneously. We employ genetic similarity kernels from the logistic kernel machine test (LKMT) as base-learners in a boosting algorithm. A model to explain case-control status is created iteratively by selecting pathways that improve its prediction ability. We evaluated our method in simulation studies adopting 50 pathways for different sample sizes and genetic effect strengths. Additionally, we included an exemplary application of kernel boosting to a rheumatoid arthritis and a lung cancer dataset. Simulations indicate that kernel boosting outperforms the LKMT in certain genetic scenarios. Applications to GWAS data on rheumatoid arthritis and lung cancer resulted in sparse models which were based on pathways interpretable in a clinical sense. Kernel boosting is highly flexible in terms of considered variables and overcomes the problem of multiple testing. Additionally, it enables the prediction of clinical outcomes. Thus, kernel boosting constitutes a new, powerful tool in the analysis of GWAS data and towards the understanding of biological processes involved in disease susceptibility.

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

    Energy Technology Data Exchange (ETDEWEB)

    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. Methods of nonlinear analysis

    CERN Document Server

    Bellman, Richard Ernest

    1970-01-01

    In this book, we study theoretical and practical aspects of computing methods for mathematical modelling of nonlinear systems. A number of computing techniques are considered, such as methods of operator approximation with any given accuracy; operator interpolation techniques including a non-Lagrange interpolation; methods of system representation subject to constraints associated with concepts of causality, memory and stationarity; methods of system representation with an accuracy that is the best within a given class of models; methods of covariance matrix estimation;methods for low-rank mat

  9. Mining pathway associations for disease-related pathway activity analysis based on gene expression and methylation data.

    Science.gov (United States)

    Lee, Hyeonjeong; Shin, Miyoung

    2017-01-01

    The problem of discovering genetic markers as disease signatures is of great significance for the successful diagnosis, treatment, and prognosis of complex diseases. Even if many earlier studies worked on identifying disease markers from a variety of biological resources, they mostly focused on the markers of genes or gene-sets (i.e., pathways). However, these markers may not be enough to explain biological interactions between genetic variables that are related to diseases. Thus, in this study, our aim is to investigate distinctive associations among active pathways (i.e., pathway-sets) shown each in case and control samples which can be observed from gene expression and/or methylation data. The pathway-sets are obtained by identifying a set of associated pathways that are often active together over a significant number of class samples. For this purpose, gene expression or methylation profiles are first analyzed to identify significant (active) pathways via gene-set enrichment analysis. Then, regarding these active pathways, an association rule mining approach is applied to examine interesting pathway-sets in each class of samples (case or control). By doing so, the sets of associated pathways often working together in activity profiles are finally chosen as our distinctive signature of each class. The identified pathway-sets are aggregated into a pathway activity network (PAN), which facilitates the visualization of differential pathway associations between case and control samples. From our experiments with two publicly available datasets, we could find interesting PAN structures as the distinctive signatures of breast cancer and uterine leiomyoma cancer, respectively. Our pathway-set markers were shown to be superior or very comparable to other genetic markers (such as genes or gene-sets) in disease classification. Furthermore, the PAN structure, which can be constructed from the identified markers of pathway-sets, could provide deeper insights into

  10. Analysis of Stomatal Patterning in Selected Mutants of MAPK Pathways

    KAUST Repository

    Felemban, Abrar

    2016-05-01

    Stomata are cellular valves in plants that play an essential role in the regulation of gas exchange and are distributed in the epidermis of aerial organs. In Arabidopsis thaliana, stomatal production and development are coordinated by the mitogen-activated protein kinase (MAPK) signalling pathway, which modulates a variety of other processes, including cell proliferation, regulation of cytokinesis, programed cell death, and response to abiotic and biotic stress. The environment also plays a role in stomatal development, by influencing the frequency at which stomata develop in leaves. This thesis presents an analysis of stomatal development in Arabidopsis mutants in two MAPK pathways: MEKK1-MKK1/MKK2-MPK4, and MAP3K17/18-MKK3. Obtained results demonstrate the effect of stress conditions on stomatal development and specify the involvement of analysed MAPK in stomatal patterning. First, both analysed pathways modulate stomatal patterning in Arabidopsis cotyledons. Second, plant growth-promoting bacteria tested enhance stomatal density and affect guard cell morphology. Third, the sucrose or mannitol treatment increases defects in stomatal patterning. Finally, salt stress or high temperature can suppress stomatal defects in mutants of the MEKK1-MKK1/MKK2-MPK4 pathway.

  11. Pathways to Medical Home Recognition: A Qualitative Comparative Analysis of the PCMH Transformation Process.

    Science.gov (United States)

    Mendel, Peter; Chen, Emily K; Green, Harold D; Armstrong, Courtney; Timbie, Justin W; Kress, Amii M; Friedberg, Mark W; Kahn, Katherine L

    2017-12-15

    To understand the process of practice transformation by identifying pathways for attaining patient-centered medical home (PCMH) recognition. The CMS Federally Qualified Health Center (FQHC) Advanced Primary Care Practice Demonstration was designed to help FQHCs achieve NCQA Level 3 PCMH recognition and improve patient outcomes. We used a stratified random sample of 20 (out of 503) participating sites for this analysis. We developed a conceptual model of structural, cultural, and implementation factors affecting PCMH transformation based on literature and initial qualitative interview themes. We then used conventional cross-case analysis, followed by qualitative comparative analysis (QCA), a cross-case method based on Boolean logic algorithms, to systematically identify pathways (i.e., combinations of factors) associated with attaining-or not attaining-Level 3 recognition. Site-level indicators were derived from semistructured interviews with site leaders at two points in time (mid- and late-implementation) and administrative data collected prior to and during the demonstration period. The QCA results identified five distinct pathways to attaining PCMH recognition and four distinct pathways to not attaining recognition by the end of the demonstration. Across these pathways, one condition (change leader capacity) was common to all pathways for attaining recognition, and another (previous improvement or recognition experience) was absent in all pathways for not attaining recognition. In general, sites could compensate for deficiencies in one factor with capacity in others, but they needed a threshold of strengths in cultural and implementation factors to attain PCMH recognition. Future efforts at primary care transformation should take into account multiple pathways sites may pursue. Sites should be assessed on key cultural and implementation factors, in addition to structural components, in order to differentiate interventions and technical assistance. © Health

  12. PyPathway: Python Package for Biological Network Analysis and Visualization.

    Science.gov (United States)

    Xu, Yang; Luo, Xiao-Chun

    2018-05-01

    Life science studies represent one of the biggest generators of large data sets, mainly because of rapid sequencing technological advances. Biological networks including interactive networks and human curated pathways are essential to understand these high-throughput data sets. Biological network analysis offers a method to explore systematically not only the molecular complexity of a particular disease but also the molecular relationships among apparently distinct phenotypes. Currently, several packages for Python community have been developed, such as BioPython and Goatools. However, tools to perform comprehensive network analysis and visualization are still needed. Here, we have developed PyPathway, an extensible free and open source Python package for functional enrichment analysis, network modeling, and network visualization. The network process module supports various interaction network and pathway databases such as Reactome, WikiPathway, STRING, and BioGRID. The network analysis module implements overrepresentation analysis, gene set enrichment analysis, network-based enrichment, and de novo network modeling. Finally, the visualization and data publishing modules enable users to share their analysis by using an easy web application. For package availability, see the first Reference.

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

    Directory of Open Access Journals (Sweden)

    Potkin Steven G

    2011-04-01

    Full Text Available Abstract 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

  14. A Bayesian method for identifying missing enzymes in predicted metabolic pathway databases

    Directory of Open Access Journals (Sweden)

    Karp Peter D

    2004-06-01

    Full Text Available Abstract Background The PathoLogic program constructs Pathway/Genome databases by using a genome's annotation to predict the set of metabolic pathways present in an organism. PathoLogic determines the set of reactions composing those pathways from the enzymes annotated in the organism's genome. Most annotation efforts fail to assign function to 40–60% of sequences. In addition, large numbers of sequences may have non-specific annotations (e.g., thiolase family protein. Pathway holes occur when a genome appears to lack the enzymes needed to catalyze reactions in a pathway. If a protein has not been assigned a specific function during the annotation process, any reaction catalyzed by that protein will appear as a missing enzyme or pathway hole in a Pathway/Genome database. Results We have developed a method that efficiently combines homology and pathway-based evidence to identify candidates for filling pathway holes in Pathway/Genome databases. Our program not only identifies potential candidate sequences for pathway holes, but combines data from multiple, heterogeneous sources to assess the likelihood that a candidate has the required function. Our algorithm emulates the manual sequence annotation process, considering not only evidence from homology searches, but also considering evidence from genomic context (i.e., is the gene part of an operon? and functional context (e.g., are there functionally-related genes nearby in the genome? to determine the posterior belief that a candidate has the required function. The method can be applied across an entire metabolic pathway network and is generally applicable to any pathway database. The program uses a set of sequences encoding the required activity in other genomes to identify candidate proteins in the genome of interest, and then evaluates each candidate by using a simple Bayes classifier to determine the probability that the candidate has the desired function. We achieved 71% precision at a

  15. Using Formal Concept Analysis to Create Pathways through Museum Collections

    DEFF Research Database (Denmark)

    Wray, Tim; Eklund, Peter

    2014-01-01

    This paper presents A Place for Art - an iPad app that allows users to explore an art collection via semantically linked pathways that are generated using Formal Concept Analysis. The app embraces the information seeking approach of exploration and is based on the idea that showing context...... and relationships among objects in a museum collection augments an interpretive experience. The fundamental interaction metaphor inherent in A Place for Art relies on Formal Concept Analysis so the interface has embedded within it the semantic clustering features of machine learning in artificial intelligence....

  16. Extending in silico mechanism-of-action analysis by annotating targets with pathways: application to cellular cytotoxicity readouts.

    Science.gov (United States)

    Liggi, Sonia; Drakakis, Georgios; Koutsoukas, Alexios; Cortes-Ciriano, Isidro; Martínez-Alonso, Patricia; Malliavin, Thérèse E; Velazquez-Campoy, Adrian; Brewerton, Suzanne C; Bodkin, Michael J; Evans, David A; Glen, Robert C; Carrodeguas, José Alberto; Bender, Andreas

    2014-01-01

    An in silico mechanism-of-action analysis protocol was developed, comprising molecule bioactivity profiling, annotation of predicted targets with pathways and calculation of enrichment factors to highlight targets and pathways more likely to be implicated in the studied phenotype. The method was applied to a cytotoxicity phenotypic endpoint, with enriched targets/pathways found to be statistically significant when compared with 100 random datasets. Application on a smaller apoptotic set (10 molecules) did not allowed to obtain statistically relevant results, suggesting that the protocol requires modification such as analysis of the most frequently predicted targets/annotated pathways. Pathway annotations improved the mechanism-of-action information gained by target prediction alone, allowing a better interpretation of the predictions and providing better mapping of targets onto pathways.

  17. Multivariate analysis: models and method

    International Nuclear Information System (INIS)

    Sanz Perucha, J.

    1990-01-01

    Data treatment techniques are increasingly used since computer methods result of wider access. Multivariate analysis consists of a group of statistic methods that are applied to study objects or samples characterized by multiple values. A final goal is decision making. The paper describes the models and methods of multivariate analysis

  18. Multivariate analysis methods in physics

    International Nuclear Information System (INIS)

    Wolter, M.

    2007-01-01

    A review of multivariate methods based on statistical training is given. Several multivariate methods useful in high-energy physics analysis are discussed. Selected examples from current research in particle physics are discussed, both from the on-line trigger selection and from the off-line analysis. Also statistical training methods are presented and some new application are suggested [ru

  19. Methods in algorithmic analysis

    CERN Document Server

    Dobrushkin, Vladimir A

    2009-01-01

    …helpful to any mathematics student who wishes to acquire a background in classical probability and analysis … This is a remarkably beautiful book that would be a pleasure for a student to read, or for a teacher to make into a year's course.-Harvey Cohn, Computing Reviews, May 2010

  20. Communication Network Analysis Methods.

    Science.gov (United States)

    Farace, Richard V.; Mabee, Timothy

    This paper reviews a variety of analytic procedures that can be applied to network data, discussing the assumptions and usefulness of each procedure when applied to the complexity of human communication. Special attention is paid to the network properties measured or implied by each procedure. Factor analysis and multidimensional scaling are among…

  1. Complementing Gender Analysis Methods.

    Science.gov (United States)

    Kumar, Anant

    2016-01-01

    The existing gender analysis frameworks start with a premise that men and women are equal and should be treated equally. These frameworks give emphasis on equal distribution of resources between men and women and believe that this will bring equality which is not always true. Despite equal distribution of resources, women tend to suffer and experience discrimination in many areas of their lives such as the power to control resources within social relationships, and the need for emotional security and reproductive rights within interpersonal relationships. These frameworks believe that patriarchy as an institution plays an important role in women's oppression, exploitation, and it is a barrier in their empowerment and rights. Thus, some think that by ensuring equal distribution of resources and empowering women economically, institutions like patriarchy can be challenged. These frameworks are based on proposed equality principle which puts men and women in competing roles. Thus, the real equality will never be achieved. Contrary to the existing gender analysis frameworks, the Complementing Gender Analysis framework proposed by the author provides a new approach toward gender analysis which not only recognizes the role of economic empowerment and equal distribution of resources but suggests to incorporate the concept and role of social capital, equity, and doing gender in gender analysis which is based on perceived equity principle, putting men and women in complementing roles that may lead to equality. In this article the author reviews the mainstream gender theories in development from the viewpoint of the complementary roles of gender. This alternative view is argued based on existing literature and an anecdote of observations made by the author. While criticizing the equality theory, the author offers equity theory in resolving the gender conflict by using the concept of social and psychological capital.

  2. An overview of bioinformatics methods for modeling biological pathways in yeast.

    Science.gov (United States)

    Hou, Jie; Acharya, Lipi; Zhu, Dongxiao; Cheng, Jianlin

    2016-03-01

    The advent of high-throughput genomics techniques, along with the completion of genome sequencing projects, identification of protein-protein interactions and reconstruction of genome-scale pathways, has accelerated the development of systems biology research in the yeast organism Saccharomyces cerevisiae In particular, discovery of biological pathways in yeast has become an important forefront in systems biology, which aims to understand the interactions among molecules within a cell leading to certain cellular processes in response to a specific environment. While the existing theoretical and experimental approaches enable the investigation of well-known pathways involved in metabolism, gene regulation and signal transduction, bioinformatics methods offer new insights into computational modeling of biological pathways. A wide range of computational approaches has been proposed in the past for reconstructing biological pathways from high-throughput datasets. Here we review selected bioinformatics approaches for modeling biological pathways inS. cerevisiae, including metabolic pathways, gene-regulatory pathways and signaling pathways. We start with reviewing the research on biological pathways followed by discussing key biological databases. In addition, several representative computational approaches for modeling biological pathways in yeast are discussed. © The Author 2015. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.

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

    Science.gov (United States)

    Ataman, Meric; Hatzimanikatis, Vassily

    2015-12-01

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

  4. Penalized differential pathway analysis of integrative oncogenomics studies.

    Science.gov (United States)

    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.

  5. Interleukin-2 signaling pathway analysis by quantitative phosphoproteomics

    DEFF Research Database (Denmark)

    Osinalde, Nerea; Moss, Helle; Arrizabalaga, Onetsine

    2011-01-01

    among which 79 were found with increased abundance in the tyrosine-phosphorylated complexes, including several previously not reported IL-2 downstream effectors. Combinatorial site-specific phosphoproteomic analysis resulted in identification of 99 phosphorylated sites mapping to the identified proteins...... with increased abundance in the tyrosine-phosphorylated complexes, of which 34 were not previously described. In addition, chemical inhibition of the identified IL-2-mediated JAK, PI3K and MAPK signaling pathways, resulted in distinct alteration on the IL-2 dependent proliferation....

  6. STOCHASTIC METHODS IN RISK ANALYSIS

    Directory of Open Access Journals (Sweden)

    Vladimíra OSADSKÁ

    2017-06-01

    Full Text Available In this paper, we review basic stochastic methods which can be used to extend state-of-the-art deterministic analytical methods for risk analysis. We can conclude that the standard deterministic analytical methods highly depend on the practical experience and knowledge of the evaluator and therefore, the stochastic methods should be introduced. The new risk analysis methods should consider the uncertainties in input values. We present how large is the impact on the results of the analysis solving practical example of FMECA with uncertainties modelled using Monte Carlo sampling.

  7. Sensitivity and uncertainty analysis of the PATHWAY radionuclide transport model

    International Nuclear Information System (INIS)

    Otis, M.D.

    1983-01-01

    Procedures were developed for the uncertainty and sensitivity analysis of a dynamic model of radionuclide transport through human food chains. Uncertainty in model predictions was estimated by propagation of parameter uncertainties using a Monte Carlo simulation technique. Sensitivity of model predictions to individual parameters was investigated using the partial correlation coefficient of each parameter with model output. Random values produced for the uncertainty analysis were used in the correlation analysis for sensitivity. These procedures were applied to the PATHWAY model which predicts concentrations of radionuclides in foods grown in Nevada and Utah and exposed to fallout during the period of atmospheric nuclear weapons testing in Nevada. Concentrations and time-integrated concentrations of iodine-131, cesium-136, and cesium-137 in milk and other foods were investigated. 9 figs., 13 tabs

  8. Enzyme sequence similarity improves the reaction alignment method for cross-species pathway comparison

    Energy Technology Data Exchange (ETDEWEB)

    Ovacik, Meric A. [Chemical and Biochemical Engineering Department, Rutgers University, Piscataway, NJ 08854 (United States); Androulakis, Ioannis P., E-mail: yannis@rci.rutgers.edu [Chemical and Biochemical Engineering Department, Rutgers University, Piscataway, NJ 08854 (United States); Biomedical Engineering Department, Rutgers University, Piscataway, NJ 08854 (United States)

    2013-09-15

    Pathway-based information has become an important source of information for both establishing evolutionary relationships and understanding the mode of action of a chemical or pharmaceutical among species. Cross-species comparison of pathways can address two broad questions: comparison in order to inform evolutionary relationships and to extrapolate species differences used in a number of different applications including drug and toxicity testing. Cross-species comparison of metabolic pathways is complex as there are multiple features of a pathway that can be modeled and compared. Among the various methods that have been proposed, reaction alignment has emerged as the most successful at predicting phylogenetic relationships based on NCBI taxonomy. We propose an improvement of the reaction alignment method by accounting for sequence similarity in addition to reaction alignment method. Using nine species, including human and some model organisms and test species, we evaluate the standard and improved comparison methods by analyzing glycolysis and citrate cycle pathways conservation. In addition, we demonstrate how organism comparison can be conducted by accounting for the cumulative information retrieved from nine pathways in central metabolism as well as a more complete study involving 36 pathways common in all nine species. Our results indicate that reaction alignment with enzyme sequence similarity results in a more accurate representation of pathway specific cross-species similarities and differences based on NCBI taxonomy.

  9. Enzyme sequence similarity improves the reaction alignment method for cross-species pathway comparison

    International Nuclear Information System (INIS)

    Ovacik, Meric A.; Androulakis, Ioannis P.

    2013-01-01

    Pathway-based information has become an important source of information for both establishing evolutionary relationships and understanding the mode of action of a chemical or pharmaceutical among species. Cross-species comparison of pathways can address two broad questions: comparison in order to inform evolutionary relationships and to extrapolate species differences used in a number of different applications including drug and toxicity testing. Cross-species comparison of metabolic pathways is complex as there are multiple features of a pathway that can be modeled and compared. Among the various methods that have been proposed, reaction alignment has emerged as the most successful at predicting phylogenetic relationships based on NCBI taxonomy. We propose an improvement of the reaction alignment method by accounting for sequence similarity in addition to reaction alignment method. Using nine species, including human and some model organisms and test species, we evaluate the standard and improved comparison methods by analyzing glycolysis and citrate cycle pathways conservation. In addition, we demonstrate how organism comparison can be conducted by accounting for the cumulative information retrieved from nine pathways in central metabolism as well as a more complete study involving 36 pathways common in all nine species. Our results indicate that reaction alignment with enzyme sequence similarity results in a more accurate representation of pathway specific cross-species similarities and differences based on NCBI taxonomy

  10. Method to determine transcriptional regulation pathways in organisms

    Science.gov (United States)

    Gardner, Timothy S.; Collins, James J.; Hayete, Boris; Faith, Jeremiah

    2012-11-06

    The invention relates to computer-implemented methods and systems for identifying regulatory relationships between expressed regulating polypeptides and targets of the regulatory activities of such regulating polypeptides. More specifically, the invention provides a new method for identifying regulatory dependencies between biochemical species in a cell. In particular embodiments, provided are computer-implemented methods for identifying a regulatory interaction between a transcription factor and a gene target of the transcription factor, or between a transcription factor and a set of gene targets of the transcription factor. Further provided are genome-scale methods for predicting regulatory interactions between a set of transcription factors and a corresponding set of transcriptional target substrates thereof.

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

    Directory of Open Access Journals (Sweden)

    Marconato Laura

    2009-03-01

    Full Text Available Abstract 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.

  12. Basic methods of isotope analysis

    International Nuclear Information System (INIS)

    Ochkin, A.V.; Rozenkevich, M.B.

    2000-01-01

    The bases of the most applied methods of the isotope analysis are briefly presented. The possibilities and analytical characteristics of the mass-spectrometric, spectral, radiochemical and special methods of the isotope analysis, including application of the magnetic resonance, chromatography and refractometry, are considered [ru

  13. Pathway-based factor analysis of gene expression data produces highly heritable phenotypes that associate with age.

    Science.gov (United States)

    Anand Brown, Andrew; Ding, Zhihao; Viñuela, Ana; Glass, Dan; Parts, Leopold; Spector, Tim; Winn, John; Durbin, Richard

    2015-03-09

    Statistical factor analysis methods have previously been used to remove noise components from high-dimensional data prior to genetic association mapping and, in a guided fashion, to summarize biologically relevant sources of variation. Here, we show how the derived factors summarizing pathway expression can be used to analyze the relationships between expression, heritability, and aging. We used skin gene expression data from 647 twins from the MuTHER Consortium and applied factor analysis to concisely summarize patterns of gene expression to remove broad confounding influences and to produce concise pathway-level phenotypes. We derived 930 "pathway phenotypes" that summarized patterns of variation across 186 KEGG pathways (five phenotypes per pathway). We identified 69 significant associations of age with phenotype from 57 distinct KEGG pathways at a stringent Bonferroni threshold ([Formula: see text]). These phenotypes are more heritable ([Formula: see text]) than gene expression levels. On average, expression levels of 16% of genes within these pathways are associated with age. Several significant pathways relate to metabolizing sugars and fatty acids; others relate to insulin signaling. We have demonstrated that factor analysis methods combined with biological knowledge can produce more reliable phenotypes with less stochastic noise than the individual gene expression levels, which increases our power to discover biologically relevant associations. These phenotypes could also be applied to discover associations with other environmental factors. Copyright © 2015 Brown et al.

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

    Science.gov (United States)

    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.

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

    Directory of Open Access Journals (Sweden)

    Miranda van Uitert

    Full Text Available 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.

  16. RaMP: A Comprehensive Relational Database of Metabolomics Pathways for Pathway Enrichment Analysis of Genes and Metabolites.

    Science.gov (United States)

    Zhang, Bofei; Hu, Senyang; Baskin, Elizabeth; Patt, Andrew; Siddiqui, Jalal K; Mathé, Ewy A

    2018-02-22

    The value of metabolomics in translational research is undeniable, and metabolomics data are increasingly generated in large cohorts. The functional interpretation of disease-associated metabolites though is difficult, and the biological mechanisms that underlie cell type or disease-specific metabolomics profiles are oftentimes unknown. To help fully exploit metabolomics data and to aid in its interpretation, analysis of metabolomics data with other complementary omics data, including transcriptomics, is helpful. To facilitate such analyses at a pathway level, we have developed RaMP (Relational database of Metabolomics Pathways), which combines biological pathways from the Kyoto Encyclopedia of Genes and Genomes (KEGG), Reactome, WikiPathways, and the Human Metabolome DataBase (HMDB). To the best of our knowledge, an off-the-shelf, public database that maps genes and metabolites to biochemical/disease pathways and can readily be integrated into other existing software is currently lacking. For consistent and comprehensive analysis, RaMP enables batch and complex queries (e.g., list all metabolites involved in glycolysis and lung cancer), can readily be integrated into pathway analysis tools, and supports pathway overrepresentation analysis given a list of genes and/or metabolites of interest. For usability, we have developed a RaMP R package (https://github.com/Mathelab/RaMP-DB), including a user-friendly RShiny web application, that supports basic simple and batch queries, pathway overrepresentation analysis given a list of genes or metabolites of interest, and network visualization of gene-metabolite relationships. The package also includes the raw database file (mysql dump), thereby providing a stand-alone downloadable framework for public use and integration with other tools. In addition, the Python code needed to recreate the database on another system is also publicly available (https://github.com/Mathelab/RaMP-BackEnd). Updates for databases in RaMP will be

  17. PathwaySplice: An R package for unbiased pathway analysis of alternative splicing in RNA-Seq data.

    Science.gov (United States)

    Yan, Aimin; Ban, Yuguang; Gao, Zhen; Chen, Xi; Wang, Lily

    2018-04-24

    Pathway analysis of alternative splicing would be biased without accounting for the different number of exons or junctions associated with each gene, because genes with higher number of exons or junctions are more likely to be included in the "significant" gene list in alternative splicing. We present PathwaySplice, an R package that (1) Performs pathway analysis that explicitly adjusts for the number of exons or junctions associated with each gene; (2) Visualizes selection bias due to different number of exons or junctions for each gene and formally tests for presence of bias using logistic regression; (3) Supports gene sets based on the Gene Ontology terms, as well as more broadly defined gene sets (e.g. MSigDB) or user defined gene sets; (4) Identifies the significant genes driving pathway significance and (5) Organizes significant pathways with an enrichment map, where pathways with large number of overlapping genes are grouped together in a network graph. https://bioconductor.org/packages/release/bioc/html/PathwaySplice.html. lily.wangg@gmail.com, xi.steven.chen@gmail.com.

  18. Integrative analysis of RUNX1 downstream pathways and target genes

    Directory of Open Access Journals (Sweden)

    Liu Marjorie

    2008-07-01

    Full Text Available Abstract Background The RUNX1 transcription factor gene is frequently mutated in sporadic myeloid and lymphoid leukemia through translocation, point mutation or amplification. It is also responsible for a familial platelet disorder with predisposition to acute myeloid leukemia (FPD-AML. The disruption of the largely unknown biological pathways controlled by RUNX1 is likely to be responsible for the development of leukemia. We have used multiple microarray platforms and bioinformatic techniques to help identify these biological pathways to aid in the understanding of why RUNX1 mutations lead to leukemia. Results Here we report genes regulated either directly or indirectly by RUNX1 based on the study of gene expression profiles generated from 3 different human and mouse platforms. The platforms used were global gene expression profiling of: 1 cell lines with RUNX1 mutations from FPD-AML patients, 2 over-expression of RUNX1 and CBFβ, and 3 Runx1 knockout mouse embryos using either cDNA or Affymetrix microarrays. We observe that our datasets (lists of differentially expressed genes significantly correlate with published microarray data from sporadic AML patients with mutations in either RUNX1 or its cofactor, CBFβ. A number of biological processes were identified among the differentially expressed genes and functional assays suggest that heterozygous RUNX1 point mutations in patients with FPD-AML impair cell proliferation, microtubule dynamics and possibly genetic stability. In addition, analysis of the regulatory regions of the differentially expressed genes has for the first time systematically identified numerous potential novel RUNX1 target genes. Conclusion This work is the first large-scale study attempting to identify the genetic networks regulated by RUNX1, a master regulator in the development of the hematopoietic system and leukemia. The biological pathways and target genes controlled by RUNX1 will have considerable importance in disease

  19. Probabilistic methods for rotordynamics analysis

    Science.gov (United States)

    Wu, Y.-T.; Torng, T. Y.; Millwater, H. R.; Fossum, A. F.; Rheinfurth, M. H.

    1991-01-01

    This paper summarizes the development of the methods and a computer program to compute the probability of instability of dynamic systems that can be represented by a system of second-order ordinary linear differential equations. Two instability criteria based upon the eigenvalues or Routh-Hurwitz test functions are investigated. Computational methods based on a fast probability integration concept and an efficient adaptive importance sampling method are proposed to perform efficient probabilistic analysis. A numerical example is provided to demonstrate the methods.

  20. Pathway Analysis of miR-181a in Hypopharyngeal Squamous Cell ...

    African Journals Online (AJOL)

    syakima

    2012-03-15

    Mar 15, 2012 ... Key words: MicroRNA, head and neck cancer, miR-181a, pathway analysis, luciferase assay, FaDu cell line, transfection ..... prostate carcinoma and glioblastoma cells. Nucleic Acids .... WNT pathway in oral cancer: epigenetic.

  1. Ensemble Modeling for Robustness Analysis in engineering non-native metabolic pathways.

    Science.gov (United States)

    Lee, Yun; Lafontaine Rivera, Jimmy G; Liao, James C

    2014-09-01

    Metabolic pathways in cells must be sufficiently robust to tolerate fluctuations in expression levels and changes in environmental conditions. Perturbations in expression levels may lead to system failure due to the disappearance of a stable steady state. Increasing evidence has suggested that biological networks have evolved such that they are intrinsically robust in their network structure. In this article, we presented Ensemble Modeling for Robustness Analysis (EMRA), which combines a continuation method with the Ensemble Modeling approach, for investigating the robustness issue of non-native pathways. EMRA investigates a large ensemble of reference models with different parameters, and determines the effects of parameter drifting until a bifurcation point, beyond which a stable steady state disappears and system failure occurs. A pathway is considered to have high bifurcational robustness if the probability of system failure is low in the ensemble. To demonstrate the utility of EMRA, we investigate the bifurcational robustness of two synthetic central metabolic pathways that achieve carbon conservation: non-oxidative glycolysis and reverse glyoxylate cycle. With EMRA, we determined the probability of system failure of each design and demonstrated that alternative designs of these pathways indeed display varying degrees of bifurcational robustness. Furthermore, we demonstrated that target selection for flux improvement should consider the trade-offs between robustness and performance. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

  2. Analysis of Precision of Activation Analysis Method

    DEFF Research Database (Denmark)

    Heydorn, Kaj; Nørgaard, K.

    1973-01-01

    The precision of an activation-analysis method prescribes the estimation of the precision of a single analytical result. The adequacy of these estimates to account for the observed variation between duplicate results from the analysis of different samples and materials, is tested by the statistic T...

  3. Pathway analysis of GWAS provides new insights into genetic susceptibility to 3 inflammatory diseases.

    Directory of Open Access Journals (Sweden)

    Hariklia Eleftherohorinou

    2009-11-01

    Full Text Available Although the introduction of genome-wide association studies (GWAS have greatly increased the number of genes associated with common diseases, only a small proportion of the predicted genetic contribution has so far been elucidated. Studying the cumulative variation of polymorphisms in multiple genes acting in functional pathways may provide a complementary approach to the more common single SNP association approach in understanding genetic determinants of common disease. We developed a novel pathway-based method to assess the combined contribution of multiple genetic variants acting within canonical biological pathways and applied it to data from 14,000 UK individuals with 7 common diseases. We tested inflammatory pathways for association with Crohn's disease (CD, rheumatoid arthritis (RA and type 1 diabetes (T1D with 4 non-inflammatory diseases as controls. Using a variable selection algorithm, we identified variants responsible for the pathway association and evaluated their use for disease prediction using a 10 fold cross-validation framework in order to calculate out-of-sample area under the Receiver Operating Curve (AUC. The generalisability of these predictive models was tested on an independent birth cohort from Northern Finland. Multiple canonical inflammatory pathways showed highly significant associations (p 10(-3-10(-20 with CD, T1D and RA. Variable selection identified on average a set of 205 SNPs (149 genes for T1D, 350 SNPs (189 genes for RA and 493 SNPs (277 genes for CD. The pattern of polymorphisms at these SNPS were found to be highly predictive of T1D (91% AUC and RA (85% AUC, and weakly predictive of CD (60% AUC. The predictive ability of the T1D model (without any parameter refitting had good predictive ability (79% AUC in the Finnish cohort. Our analysis suggests that genetic contribution to common inflammatory diseases operates through multiple genes interacting in functional pathways.

  4. Analysis apparatus and method of analysis

    International Nuclear Information System (INIS)

    1976-01-01

    A continuous streaming method developed for the excution of immunoassays is described in this patent. In addition, a suitable apparatus for the method was developed whereby magnetic particles are automatically employed for the consecutive analysis of a series of liquid samples via the RIA technique

  5. Nonlinear programming analysis and methods

    CERN Document Server

    Avriel, Mordecai

    2012-01-01

    This text provides an excellent bridge between principal theories and concepts and their practical implementation. Topics include convex programming, duality, generalized convexity, analysis of selected nonlinear programs, techniques for numerical solutions, and unconstrained optimization methods.

  6. Chemical methods of rock analysis

    National Research Council Canada - National Science Library

    Jeffery, P. G; Hutchison, D

    1981-01-01

    A practical guide to the methods in general use for the complete analysis of silicate rock material and for the determination of all those elements present in major, minor or trace amounts in silicate...

  7. Pathway analysis for a contaminated landfill in Middlesex, New Jersey

    International Nuclear Information System (INIS)

    Yu, C.; Merry-Libby, P.; Yang, J.Y.

    1985-01-01

    Under the Formerly Utilized Sites Remedial Action Program, the US Department of Energy began excavating contaminated materials from the Middlesex Municipal landfill in 1984. A total of 16,000 m 3 of landfill materials covering a 0.2-ha area was excavated, of which 11,000 m 3 was contaminated and has been transported to the nearby sampling plant site for interim storage. Based on the pathway analysis for the onsite and near-site resident scenarios, the radiation dose rates and radionuclide concentrations in groundwater would be below the regulatory requirements for both the short-term and long-term scenarios. Hence, the potential health risks to maximally exposed individuals due to radioactive releases from the Middlesex landfill would be insignificant

  8. A knowledge-based T2-statistic to perform pathway analysis for quantitative proteomic data.

    Science.gov (United States)

    Lai, En-Yu; Chen, Yi-Hau; Wu, Kun-Pin

    2017-06-01

    Approaches to identify significant pathways from high-throughput quantitative data have been developed in recent years. Still, the analysis of proteomic data stays difficult because of limited sample size. This limitation also leads to the practice of using a competitive null as common approach; which fundamentally implies genes or proteins as independent units. The independent assumption ignores the associations among biomolecules with similar functions or cellular localization, as well as the interactions among them manifested as changes in expression ratios. Consequently, these methods often underestimate the associations among biomolecules and cause false positives in practice. Some studies incorporate the sample covariance matrix into the calculation to address this issue. However, sample covariance may not be a precise estimation if the sample size is very limited, which is usually the case for the data produced by mass spectrometry. In this study, we introduce a multivariate test under a self-contained null to perform pathway analysis for quantitative proteomic data. The covariance matrix used in the test statistic is constructed by the confidence scores retrieved from the STRING database or the HitPredict database. We also design an integrating procedure to retain pathways of sufficient evidence as a pathway group. The performance of the proposed T2-statistic is demonstrated using five published experimental datasets: the T-cell activation, the cAMP/PKA signaling, the myoblast differentiation, and the effect of dasatinib on the BCR-ABL pathway are proteomic datasets produced by mass spectrometry; and the protective effect of myocilin via the MAPK signaling pathway is a gene expression dataset of limited sample size. Compared with other popular statistics, the proposed T2-statistic yields more accurate descriptions in agreement with the discussion of the original publication. We implemented the T2-statistic into an R package T2GA, which is available at https

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

    Science.gov (United States)

    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

  10. The cardiopulmonary effects of ambient air pollution and mechanistic pathways: a comparative hierarchical pathway analysis.

    Directory of Open Access Journals (Sweden)

    Ananya Roy

    Full Text Available 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.

  11. Analysis of acyl CoA ester intermediates of the mevalonate pathway in Saccharomyces cerevisiae

    DEFF Research Database (Denmark)

    Seker, Tamay; Møller, Kasper; Nielsen, Jens

    2005-01-01

    The mevalonate pathway plays an important role in providing the cell with a number of essential precursors for the synthesis of biomass constituents. With respect to their chemical structure, the metabolites of this pathway can be divided into two groups: acyl esters [acetoacetyl CoA, acetyl Co......A, hydroxymethylglutaryl (HMG) CoA] and phosphorylated metabolites (isopentenyl pyrophosphate, dimethylallyl pyrophosphate, geranyl pyrophosphate, farnesyl pyrophosphate). In this study, we developed a method for the precise analysis of the intracellular concentration of acetoacetyl CoA, acetyl CoA and HMG CoA; and we...... used this method for quantification of these metabolites in Saccharomyces cerevisiae, both during batch growth on glucose and on galactose and in glucose-limited chemostat cultures operated at three different dilution rates. The level of the metabolites changed depending on the growth phase...

  12. Seismic design and analysis methods

    International Nuclear Information System (INIS)

    Varpasuo, P.

    1993-01-01

    Seismic load is in many areas of the world the most important loading situation from the point of view of structural strength. Taking this into account it is understandable, that there has been a strong allocation of resources in the seismic analysis during the past ten years. In this study there are three areas of the center of gravity: (1) Random vibrations; (2) Soil-structure interaction and (3) The methods for determining structural response. The solution of random vibration problems is clarified with the aid of applications in this study and from the point of view of mathematical treatment and mathematical formulations it is deemed sufficient to give the relevant sources. In the soil-structure interaction analysis the focus has been the significance of frequency dependent impedance functions. As a result it was obtained, that the description of the soil with the aid of frequency dependent impedance functions decreases the structural response and it is thus always the preferred method when compared to more conservative analysis types. From the methods to determine the C structural response the following four were tested: (1) The time history method; (2) The complex frequency-response method; (3) Response spectrum method and (4) The equivalent static force method. The time history appeared to be the most accurate method and the complex frequency-response method did have the widest area of application. (orig.). (14 refs., 35 figs.)

  13. Mapping subsurface pathways for contaminant migration at a proposed low level waste disposal site using electromagnetic methods

    International Nuclear Information System (INIS)

    Pin, F.G.; Ketelle, R.H.

    1984-01-01

    Electromagnetic methods have been used to measure apparent terrain conductivity in the downstream portion of a watershed in which a waste disposal site is proposed. At that site, the pathways for waste migration in ground water are controlled by subsurface channels. The channels are identified using isocurves of measured apparent conductivity. Two upstream channel branches are found to merge into a single downstream channel which constitutes the main drainage path out of the watershed. The identification and mapping of the ground water pathways is an important contribution to the site characterization study and the pathways analysis. The direct applications of terrain conductivity mapping to the planning of the monitoring program, the hydrogeological testing, and the modeling study are demonstrated. 7 references, 4 figures

  14. Hanford Site Composite Analysis Technical Approach Description: Groundwater Pathway Dose Calculation.

    Energy Technology Data Exchange (ETDEWEB)

    Morgans, D. L. [CH2M Hill Plateau Remediation Company, Richland, WA (United States); Lindberg, S. L. [Intera Inc., Austin, TX (United States)

    2017-09-20

    The purpose of this technical approach document (TAD) is to document the assumptions, equations, and methods used to perform the groundwater pathway radiological dose calculations for the revised Hanford Site Composite Analysis (CA). DOE M 435.1-1, states, “The composite analysis results shall be used for planning, radiation protection activities, and future use commitments to minimize the likelihood that current low-level waste disposal activities will result in the need for future corrective or remedial actions to adequately protect the public and the environment.”

  15. Comparison of pathways associated with hepatitis B- and C-infected hepatocellular carcinoma using pathway-based class discrimination method.

    Science.gov (United States)

    Lee, Sun Young; Song, Kwang Hoon; Koo, Imhoi; Lee, Kee-Ho; Suh, Kyung-Suk; Kim, Bu-Yeo

    2012-06-01

    Molecular signatures causing hepatocellular carcinoma (HCC) from chronic infection of hepatitis B virus (HBV) or hepatitis C virus (HCV) are not clearly known. Using microarray datasets composed of HCV-positive HCC or HBV-positive HCC, pathways that could discriminate tumor tissue from adjacent non-tumor liver tissue were selected by implementing nearest shrunken centroid algorithm. Cancer-related signaling pathways and lipid metabolism-related pathways were predominantly enriched in HCV-positive HCC, whereas functionally diverse pathways including immune-related pathways, cell cycle pathways, and RNA metabolism pathways were mainly enriched in HBV-positive HCC. In addition to differentially involved pathways, signaling pathways such as TGF-β, MAPK, and p53 pathways were commonly significant in both HCCs, suggesting the presence of common hepatocarcinogenesis process. The pathway clustering also verified segregation of pathways into the functional subgroups in both HCCs. This study indicates the functional distinction and similarity on the pathways implicated in the development of HCV- and/or HBV-positive HCC. Copyright © 2012 Elsevier Inc. All rights reserved.

  16. Pathway Distiller - multisource biological pathway consolidation.

    Science.gov (United States)

    Doderer, Mark S; Anguiano, Zachry; Suresh, Uthra; Dashnamoorthy, Ravi; Bishop, Alexander J R; Chen, Yidong

    2012-01-01

    One method to understand and evaluate an experiment that produces a large set of genes, such as a gene expression microarray analysis, is to identify overrepresentation or enrichment for biological pathways. Because pathways are able to functionally describe the set of genes, much effort has been made to collect curated biological pathways into publicly accessible databases. When combining disparate databases, highly related or redundant pathways exist, making their consolidation into pathway concepts essential. This will facilitate unbiased, comprehensive yet streamlined analysis of experiments that result in large gene sets. After gene set enrichment finds representative pathways for large gene sets, pathways are consolidated into representative pathway concepts. Three complementary, but different methods of pathway consolidation are explored. Enrichment Consolidation combines the set of the pathways enriched for the signature gene list through iterative combining of enriched pathways with other pathways with similar signature gene sets; Weighted Consolidation utilizes a Protein-Protein Interaction network based gene-weighting approach that finds clusters of both enriched and non-enriched pathways limited to the experiments' resultant gene list; and finally the de novo Consolidation method uses several measurements of pathway similarity, that finds static pathway clusters independent of any given experiment. We demonstrate that the three consolidation methods provide unified yet different functional insights of a resultant gene set derived from a genome-wide profiling experiment. Results from the methods are presented, demonstrating their applications in biological studies and comparing with a pathway web-based framework that also combines several pathway databases. Additionally a web-based consolidation framework that encompasses all three methods discussed in this paper, Pathway Distiller (http://cbbiweb.uthscsa.edu/PathwayDistiller), is established to allow

  17. Understanding alternative fluxes/effluxes through comparative metabolic pathway analysis of phylum actinobacteria using a simplified approach.

    Science.gov (United States)

    Verma, Mansi; Lal, Devi; Saxena, Anjali; Anand, Shailly; Kaur, Jasvinder; Kaur, Jaspreet; Lal, Rup

    2013-12-01

    Actinobacteria are known for their diverse metabolism and physiology. Some are dreadful human pathogens whereas some constitute the natural flora for human gut. Therefore, the understanding of metabolic pathways is a key feature for targeting the pathogenic bacteria without disturbing the symbiotic ones. A big challenge faced today is multiple drug resistance by Mycobacterium and other pathogens that utilize alternative fluxes/effluxes. With the availability of genome sequence, it is now feasible to conduct the comparative in silico analysis. Here we present a simplified approach to compare metabolic pathways so that the species specific enzyme may be traced and engineered for future therapeutics. The analyses of four key carbohydrate metabolic pathways, i.e., glycolysis, pyruvate metabolism, tri carboxylic acid cycle and pentose phosphate pathway suggest the presence of alternative fluxes. It was found that the upper pathway of glycolysis was highly variable in the actinobacterial genomes whereas lower glycolytic pathway was highly conserved. Likewise, pentose phosphate pathway was well conserved in contradiction to TCA cycle, which was found to be incomplete in majority of actinobacteria. The clustering based on presence and absence of genes of these metabolic pathways clearly revealed that members of different genera shared identical pathways and, therefore, provided an easy method to identify the metabolic similarities/differences between pathogenic and symbiotic organisms. The analyses could identify isoenzymes and some key enzymes that were found to be missing in some pathogenic actinobacteria. The present work defines a simple approach to explore the effluxes in four metabolic pathways within the phylum actinobacteria. The analysis clearly reflects that actinobacteria exhibit diverse routes for metabolizing substrates. The pathway comparison can help in finding the enzymes that can be used as drug targets for pathogens without effecting symbiotic organisms

  18. Identification of Key Pathways and Genes in Advanced Coronary Atherosclerosis Using Bioinformatics Analysis

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    Xiaowen Tan

    2017-01-01

    Full Text Available Background. Coronary artery atherosclerosis is a chronic inflammatory disease. This study aimed to identify the key changes of gene expression between early and advanced carotid atherosclerotic plaque in human. Methods. Gene expression dataset GSE28829 was downloaded from Gene Expression Omnibus (GEO, including 16 advanced and 13 early stage atherosclerotic plaque samples from human carotid. Differentially expressed genes (DEGs were analyzed. Results. 42,450 genes were obtained from the dataset. Top 100 up- and downregulated DEGs were listed. Functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG identification were performed. The result of functional and pathway enrichment analysis indicted that the immune system process played a critical role in the progression of carotid atherosclerotic plaque. Protein-protein interaction (PPI networks were performed either. Top 10 hub genes were identified from PPI network and top 6 modules were inferred. These genes were mainly involved in chemokine signaling pathway, cell cycle, B cell receptor signaling pathway, focal adhesion, and regulation of actin cytoskeleton. Conclusion. The present study indicated that analysis of DEGs would make a deeper understanding of the molecular mechanisms of atherosclerosis development and they might be used as molecular targets and diagnostic biomarkers for the treatment of atherosclerosis.

  19. A method for integrating and ranking the evidence for biochemical pathways by mining reactions from text

    Science.gov (United States)

    Miwa, Makoto; Ohta, Tomoko; Rak, Rafal; Rowley, Andrew; Kell, Douglas B.; Pyysalo, Sampo; Ananiadou, Sophia

    2013-01-01

    Motivation: To create, verify and maintain pathway models, curators must discover and assess knowledge distributed over the vast body of biological literature. Methods supporting these tasks must understand both the pathway model representations and the natural language in the literature. These methods should identify and order documents by relevance to any given pathway reaction. No existing system has addressed all aspects of this challenge. Method: We present novel methods for associating pathway model reactions with relevant publications. Our approach extracts the reactions directly from the models and then turns them into queries for three text mining-based MEDLINE literature search systems. These queries are executed, and the resulting documents are combined and ranked according to their relevance to the reactions of interest. We manually annotate document-reaction pairs with the relevance of the document to the reaction and use this annotation to study several ranking methods, using various heuristic and machine-learning approaches. Results: Our evaluation shows that the annotated document-reaction pairs can be used to create a rule-based document ranking system, and that machine learning can be used to rank documents by their relevance to pathway reactions. We find that a Support Vector Machine-based system outperforms several baselines and matches the performance of the rule-based system. The success of the query extraction and ranking methods are used to update our existing pathway search system, PathText. Availability: An online demonstration of PathText 2 and the annotated corpus are available for research purposes at http://www.nactem.ac.uk/pathtext2/. Contact: makoto.miwa@manchester.ac.uk Supplementary information: Supplementary data are available at Bioinformatics online. PMID:23813008

  20. Chapter 7. Cloning and analysis of natural product pathways.

    Science.gov (United States)

    Gust, Bertolt

    2009-01-01

    The identification of gene clusters of natural products has lead to an enormous wealth of information about their biosynthesis and its regulation, and about self-resistance mechanisms. Well-established routine techniques are now available for the cloning and sequencing of gene clusters. The subsequent functional analysis of the complex biosynthetic machinery requires efficient genetic tools for manipulation. Until recently, techniques for the introduction of defined changes into Streptomyces chromosomes were very time-consuming. In particular, manipulation of large DNA fragments has been challenging due to the absence of suitable restriction sites for restriction- and ligation-based techniques. The homologous recombination approach called recombineering (referred to as Red/ET-mediated recombination in this chapter) has greatly facilitated targeted genetic modifications of complex biosynthetic pathways from actinomycetes by eliminating many of the time-consuming and labor-intensive steps. This chapter describes techniques for the cloning and identification of biosynthetic gene clusters, for the generation of gene replacements within such clusters, for the construction of integrative library clones and their expression in heterologous hosts, and for the assembly of entire biosynthetic gene clusters from the inserts of individual library clones. A systematic approach toward insertional mutation of a complete Streptomyces genome is shown by the use of an in vitro transposon mutagenesis procedure.

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

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    Axel Visel

    2007-10-01

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

  2. Supply Chain Sustainability Analysis of Three Biofuel Pathways

    Energy Technology Data Exchange (ETDEWEB)

    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.

  3. Hepatic Proteomic Analysis Revealed Altered Metabolic Pathways in Insulin Resistant Akt1+/-/Akt2-/-Mice

    Science.gov (United States)

    Pedersen, Brian A; Wang, Weiwen; Taylor, Jared F; Khattab, Omar S; Chen, Yu-Han; Edwards, Robert A; Yazdi, Puya G; Wang, Ping H

    2015-01-01

    Objective The aim of this study was to identify liver proteome changes in a mouse model of severe insulin resistance and markedly decreased leptin levels. Methods Two-dimensional differential gel electrophoresis was utilized to identify liver proteome changes in AKT1+/-/AKT2-/- mice. Proteins with altered levels were identified with tandem mass spectrometry. Ingenuity Pathway analysis was performed for the interpretation of the biological significance of the observed proteomic changes. Results 11 proteins were identified from 2 biological replicates to be differentially expressed by a ratio of at least 1.3 between age-matched insulin resistant (Akt1+/-/Akt2-/-) and wild type mice. Albumin and mitochondrial ornithine aminotransferase were detected from multiple spots, which suggest post-translational modifications. Enzymes of the urea cycle were common members of top regulated pathways. Conclusion Our results help to unveil the regulation of the liver proteome underlying altered metabolism in an animal model of severe insulin resistance. PMID:26455965

  4. Integrative Analysis of Gene Expression Data Including an Assessment of Pathway Enrichment for Predicting Prostate Cancer

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    Pingzhao Hu

    2006-01-01

    Full Text Available Background: Microarray technology has been previously used to identify genes that are differentially expressed between tumour and normal samples in a single study, as well as in syntheses involving multiple studies. When integrating results from several Affymetrix microarray datasets, previous studies summarized probeset-level data, which may potentially lead to a loss of information available at the probe-level. In this paper, we present an approach for integrating results across studies while taking probe-level data into account. Additionally, we follow a new direction in the analysis of microarray expression data, namely to focus on the variation of expression phenotypes in predefined gene sets, such as pathways. This targeted approach can be helpful for revealing information that is not easily visible from the changes in the individual genes. Results: We used a recently developed method to integrate Affymetrix expression data across studies. The idea is based on a probe-level based test statistic developed for testing for differentially expressed genes in individual studies. We incorporated this test statistic into a classic random-effects model for integrating data across studies. Subsequently, we used a gene set enrichment test to evaluate the significance of enriched biological pathways in the differentially expressed genes identified from the integrative analysis. We compared statistical and biological significance of the prognostic gene expression signatures and pathways identified in the probe-level model (PLM with those in the probeset-level model (PSLM. Our integrative analysis of Affymetrix microarray data from 110 prostate cancer samples obtained from three studies reveals thousands of genes significantly correlated with tumour cell differentiation. The bioinformatics analysis, mapping these genes to the publicly available KEGG database, reveals evidence that tumour cell differentiation is significantly associated with many

  5. miR2Pathway: A Novel Analytical Method to Discover MicroRNA-mediated Dysregulated Pathways Involved in Hepatocellular Carcinoma.

    Science.gov (United States)

    Li, Chaoxing; Dinu, Valentin

    2018-03-22

    MicroRNAs (miRNAs) are small, non-coding RNAs involved in the regulation of gene expression at a post-transcriptional level. Recent studies have shown miRNAs as key regulators of a variety of biological processes, such as proliferation, differentiation, apoptosis, metabolism, etc. Aberrantly expressed miRNAs influence individual gene expression level, but rewired miRNA-mRNA connections can influence the activity of biological pathways. Here, we define rewired miRNA-mRNA connections as the differential (rewiring) effects on the activity of biological pathways between hepatocellular carcinoma (HCC) and normal phenotypes. Our work presented here uses a PageRank-based approach to measure the degree of miRNA-mediated dysregulation of biological pathways between HCC and normal samples based on rewired miRNA-mRNA connections. In our study, we regard the degree of miRNA-mediated dysregulation of biological pathways as disease risk of biological pathways. Therefore, we propose a new method, miR2Pathway, to measure and rank the degree of miRNA-mediated dysregulation of biological pathways by measuring the total differential influence of miRNAs on the activity of pathways between HCC and normal states. miR2Pathway proposed here systematically shows the first evidence for a mechanism of biological pathways being dysregulated by rewired miRNA-mRNA connections, and provides new insight into exploring mechanisms behind HCC. Thus, miR2Pathway is a novel method to identify and rank miRNA-dysregulated pathways in HCC. Copyright © 2018. Published by Elsevier Inc.

  6. SWOT ANALYSIS ON SAMPLING METHOD

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    CHIS ANCA OANA

    2014-07-01

    Full Text Available Audit sampling involves the application of audit procedures to less than 100% of items within an account balance or class of transactions. Our article aims to study audit sampling in audit of financial statements. As an audit technique largely used, in both its statistical and nonstatistical form, the method is very important for auditors. It should be applied correctly for a fair view of financial statements, to satisfy the needs of all financial users. In order to be applied correctly the method must be understood by all its users and mainly by auditors. Otherwise the risk of not applying it correctly would cause loose of reputation and discredit, litigations and even prison. Since there is not a unitary practice and methodology for applying the technique, the risk of incorrectly applying it is pretty high. The SWOT analysis is a technique used that shows the advantages, disadvantages, threats and opportunities. We applied SWOT analysis in studying the sampling method, from the perspective of three players: the audit company, the audited entity and users of financial statements. The study shows that by applying the sampling method the audit company and the audited entity both save time, effort and money. The disadvantages of the method are difficulty in applying and understanding its insight. Being largely used as an audit method and being a factor of a correct audit opinion, the sampling method’s advantages, disadvantages, threats and opportunities must be understood by auditors.

  7. Parameter-free methods distinguish Wnt pathway models and guide design of experiments

    KAUST Repository

    MacLean, Adam L.

    2015-02-17

    The canonical Wnt signaling pathway, mediated by β-catenin, is crucially involved in development, adult stem cell tissue maintenance, and a host of diseases including cancer. We analyze existing mathematical models of Wnt and compare them to a new Wnt signaling model that targets spatial localization; our aim is to distinguish between the models and distill biological insight from them. Using Bayesian methods we infer parameters for each model from mammalian Wnt signaling data and find that all models can fit this time course. We appeal to algebraic methods (concepts from chemical reaction network theory and matroid theory) to analyze the models without recourse to specific parameter values. These approaches provide insight into aspects of Wnt regulation: the new model, via control of shuttling and degradation parameters, permits multiple stable steady states corresponding to stem-like vs. committed cell states in the differentiation hierarchy. Our analysis also identifies groups of variables that should be measured to fully characterize and discriminate between competing models, and thus serves as a guide for performing minimal experiments for model comparison.

  8. GEP analysis validates high risk MDS and acute myeloid leukemia post MDS mice models and highlights novel dysregulated pathways

    Directory of Open Access Journals (Sweden)

    Laura Guerenne

    2016-01-01

    Full Text Available Abstract Background In spite of the recent discovery of genetic mutations in most myelodysplasic (MDS patients, the pathophysiology of these disorders still remains poorly understood, and only few in vivo models are available to help unravel the disease. Methods We performed global specific gene expression profiling and functional pathway analysis in purified Sca1+ cells of two MDS transgenic mouse models that mimic human high-risk MDS (HR-MDS and acute myeloid leukemia (AML post MDS, with NRASD12 and BCL2 transgenes under the control of different promoters MRP8NRASD12/tethBCL-2 or MRP8[NRASD12/hBCL-2], respectively. Results Analysis of dysregulated genes that were unique to the diseased HR-MDS and AML post MDS mice and not their founder mice pointed first to pathways that had previously been reported in MDS patients, including DNA replication/damage/repair, cell cycle, apoptosis, immune responses, and canonical Wnt pathways, further validating these models at the gene expression level. Interestingly, pathways not previously reported in MDS were discovered. These included dysregulated genes of noncanonical Wnt pathways and energy and lipid metabolisms. These dysregulated genes were not only confirmed in a different independent set of BM and spleen Sca1+ cells from the MDS mice but also in MDS CD34+ BM patient samples. Conclusions These two MDS models may thus provide useful preclinical models to target pathways previously identified in MDS patients and to unravel novel pathways highlighted by this study.

  9. Systematic enrichment analysis of gene expression profiling studies identifies consensus pathways implicated in colorectal cancer development

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    Jesús Lascorz

    2011-01-01

    Full Text Available Background: A large number of gene expression profiling (GEP studies on colorectal carcinogenesis have been performed but no reliable gene signature has been identified so far due to the lack of reproducibility in the reported genes. There is growing evidence that functionally related genes, rather than individual genes, contribute to the etiology of complex traits. We used, as a novel approach, pathway enrichment tools to define functionally related genes that are consistently up- or down-regulated in colorectal carcinogenesis. Materials and Methods: We started the analysis with 242 unique annotated genes that had been reported by any of three recent meta-analyses covering GEP studies on genes differentially expressed in carcinoma vs normal mucosa. Most of these genes (218, 91.9% had been reported in at least three GEP studies. These 242 genes were submitted to bioinformatic analysis using a total of nine tools to detect enrichment of Gene Ontology (GO categories or Kyoto Encyclopedia of Genes and Genomes (KEGG pathways. As a final consistency criterion the pathway categories had to be enriched by several tools to be taken into consideration. Results: Our pathway-based enrichment analysis identified the categories of ribosomal protein constituents, extracellular matrix receptor interaction, carbonic anhydrase isozymes, and a general category related to inflammation and cellular response as significantly and consistently overrepresented entities. Conclusions: We triaged the genes covered by the published GEP literature on colorectal carcinogenesis and subjected them to multiple enrichment tools in order to identify the consistently enriched gene categories. These turned out to have known functional relationships to cancer development and thus deserve further investigation.

  10. Aligning Event Logs to Task-Time Matrix Clinical Pathways in BPMN for Variance Analysis.

    Science.gov (United States)

    Yan, Hui; Van Gorp, Pieter; Kaymak, Uzay; Lu, Xudong; Ji, Lei; Chiau, Choo Chiap; Korsten, Hendrikus H M; Duan, Huilong

    2018-03-01

    Clinical pathways (CPs) are popular healthcare management tools to standardize care and ensure quality. Analyzing CP compliance levels and variances is known to be useful for training and CP redesign purposes. Flexible semantics of the business process model and notation (BPMN) language has been shown to be useful for the modeling and analysis of complex protocols. However, in practical cases one may want to exploit that CPs often have the form of task-time matrices. This paper presents a new method parsing complex BPMN models and aligning traces to the models heuristically. A case study on variance analysis is undertaken, where a CP from the practice and two large sets of patients data from an electronic medical record (EMR) database are used. The results demonstrate that automated variance analysis between BPMN task-time models and real-life EMR data are feasible, whereas that was not the case for the existing analysis techniques. We also provide meaningful insights for further improvement.

  11. Analysis of Stomatal Patterning in Selected Mutants of MAPK Pathways

    KAUST Repository

    Felemban, Abrar

    2016-01-01

    -activated protein kinase (MAPK) signalling pathway, which modulates a variety of other processes, including cell proliferation, regulation of cytokinesis, programed cell death, and response to abiotic and biotic stress. The environment also plays a role in stomatal

  12. Pathway-based Analysis of the Hidden Genetic Heterogeneities in Cancers

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    Xiaolei Zhao

    2014-02-01

    Full Text Available Many cancers apparently showing similar phenotypes are actually distinct at the molecular level, leading to very different responses to the same treatment. It has been recently demonstrated that pathway-based approaches are robust and reliable for genetic analysis of cancers. Nevertheless, it remains unclear whether such function-based approaches are useful in deciphering molecular heterogeneities in cancers. Therefore, we aimed to test this possibility in the present study. First, we used a NCI60 dataset to validate the ability of pathways to correctly partition samples. Next, we applied the proposed method to identify the hidden subtypes in diffuse large B-cell lymphoma (DLBCL. Finally, the clinical significance of the identified subtypes was verified using survival analysis. For the NCI60 dataset, we achieved highly accurate partitions that best fit the clinical cancer phenotypes. Subsequently, for a DLBCL dataset, we identified three hidden subtypes that showed very different 10-year overall survival rates (90%, 46% and 20% and were highly significantly (P = 0.008 correlated with the clinical survival rate. This study demonstrated that the pathway-based approach is promising for unveiling genetic heterogeneities in complex human diseases.

  13. Functional analysis of the MAPK pathways in fungi.

    Science.gov (United States)

    Martínez-Soto, Domingo; Ruiz-Herrera, José

    The Mitogen-Activated Protein Kinase (MAPK) signaling pathways constitute one of the most important and evolutionarily conserved mechanisms for the perception of extracellular information in all the eukaryotic organisms. The MAPK pathways are involved in the transfer to the cell of the information perceived from extracellular stimuli, with the final outcome of activation of different transcription factors that regulate gene expression in response to them. In all species of fungi, the MAPK pathways have important roles in their physiology and development; e.g. cell cycle control, mating, morphogenesis, response to different stresses, resistance to UV radiation and to temperature changes, cell wall assembly and integrity, degradation of cellular organelles, virulence, cell-cell signaling, fungus-plant interaction, and response to damage-associated molecular patterns (DAMPs). Considering the importance of the phylogenetically conserved MAPK pathways in fungi, an updated review of the knowledge on them is discussed in this article. This information reveals their importance, their distribution in fungal species evolutionarily distant and with different lifestyles, their organization and function, and the interactions occurring between different MAPK pathways, and with other signaling pathways, for the regulation of the most complex cellular processes. Copyright © 2017 Asociación Española de Micología. Publicado por Elsevier España, S.L.U. All rights reserved.

  14. Gene expression meta-analysis identifies metastatic pathways and transcription factors in breast cancer

    International Nuclear Information System (INIS)

    Thomassen, Mads; Tan, Qihua; Kruse, Torben A

    2008-01-01

    Metastasis is believed to progress in several steps including different pathways but the determination and understanding of these mechanisms is still fragmentary. Microarray analysis of gene expression patterns in breast tumors has been used to predict outcome in recent studies. Besides classification of outcome, these global expression patterns may reflect biological mechanisms involved in metastasis of breast cancer. Our purpose has been to investigate pathways and transcription factors involved in metastasis by use of gene expression data sets. We have analyzed 8 publicly available gene expression data sets. A global approach, 'gene set enrichment analysis' as well as an approach focusing on a subset of significantly differently regulated genes, GenMAPP, has been applied to rank pathway gene sets according to differential regulation in metastasizing tumors compared to non-metastasizing tumors. Meta-analysis has been used to determine overrepresentation of pathways and transcription factors targets, concordant deregulated in metastasizing breast tumors, in several data sets. The major findings are up-regulation of cell cycle pathways and a metabolic shift towards glucose metabolism reflected in several pathways in metastasizing tumors. Growth factor pathways seem to play dual roles; EGF and PDGF pathways are decreased, while VEGF and sex-hormone pathways are increased in tumors that metastasize. Furthermore, migration, proteasome, immune system, angiogenesis, DNA repair and several signal transduction pathways are associated to metastasis. Finally several transcription factors e.g. E2F, NFY, and YY1 are identified as being involved in metastasis. By pathway meta-analysis many biological mechanisms beyond major characteristics such as proliferation are identified. Transcription factor analysis identifies a number of key factors that support central pathways. Several previously proposed treatment targets are identified and several new pathways that may

  15. Comparative analysis of programmed cell death pathways in filamentous fungi

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    Wortman Jennifer R

    2005-12-01

    Full Text Available Abstract Background Fungi can undergo autophagic- or apoptotic-type programmed cell death (PCD on exposure to antifungal agents, developmental signals, and stress factors. Filamentous fungi can also exhibit a form of cell death called heterokaryon incompatibility (HI triggered by fusion between two genetically incompatible individuals. With the availability of recently sequenced genomes of Aspergillus fumigatus and several related species, we were able to define putative components of fungi-specific death pathways and the ancestral core apoptotic machinery shared by all fungi and metazoa. Results Phylogenetic profiling of HI-associated proteins from four Aspergilli and seven other fungal species revealed lineage-specific protein families, orphan genes, and core genes conserved across all fungi and metazoa. The Aspergilli-specific domain architectures include NACHT family NTPases, which may function as key integrators of stress and nutrient availability signals. They are often found fused to putative effector domains such as Pfs, SesB/LipA, and a newly identified domain, HET-s/LopB. Many putative HI inducers and mediators are specific to filamentous fungi and not found in unicellular yeasts. In addition to their role in HI, several of them appear to be involved in regulation of cell cycle, development and sexual differentiation. Finally, the Aspergilli possess many putative downstream components of the mammalian apoptotic machinery including several proteins not found in the model yeast, Saccharomyces cerevisiae. Conclusion Our analysis identified more than 100 putative PCD associated genes in the Aspergilli, which may help expand the range of currently available treatments for aspergillosis and other invasive fungal diseases. The list includes species-specific protein families as well as conserved core components of the ancestral PCD machinery shared by fungi and metazoa.

  16. Flows method in global analysis

    International Nuclear Information System (INIS)

    Duong Minh Duc.

    1994-12-01

    We study the gradient flows method for W r,p (M,N) where M and N are Riemannian manifold and r may be less than m/p. We localize some global analysis problem by constructing gradient flows which only change the value of any u in W r,p (M,N) in a local chart of M. (author). 24 refs

  17. Microarray analysis reveals key genes and pathways in Tetralogy of Fallot

    Science.gov (United States)

    He, Yue-E; Qiu, Hui-Xian; Jiang, Jian-Bing; Wu, Rong-Zhou; Xiang, Ru-Lian; Zhang, Yuan-Hai

    2017-01-01

    The aim of the present study was to identify key genes that may be involved in the pathogenesis of Tetralogy of Fallot (TOF) using bioinformatics methods. The GSE26125 microarray dataset, which includes cardiovascular tissue samples derived from 16 children with TOF and five healthy age-matched control infants, was downloaded from the Gene Expression Omnibus database. Differential expression analysis was performed between TOF and control samples to identify differentially expressed genes (DEGs) using Student's t-test, and the R/limma package, with a log2 fold-change of >2 and a false discovery rate of <0.01 set as thresholds. The biological functions of DEGs were analyzed using the ToppGene database. The ReactomeFIViz application was used to construct functional interaction (FI) networks, and the genes in each module were subjected to pathway enrichment analysis. The iRegulon plugin was used to identify transcription factors predicted to regulate the DEGs in the FI network, and the gene-transcription factor pairs were then visualized using Cytoscape software. A total of 878 DEGs were identified, including 848 upregulated genes and 30 downregulated genes. The gene FI network contained seven function modules, which were all comprised of upregulated genes. Genes enriched in Module 1 were enriched in the following three neurological disorder-associated signaling pathways: Parkinson's disease, Alzheimer's disease and Huntington's disease. Genes in Modules 0, 3 and 5 were dominantly enriched in pathways associated with ribosomes and protein translation. The Xbox binding protein 1 transcription factor was demonstrated to be involved in the regulation of genes encoding the subunits of cytoplasmic and mitochondrial ribosomes, as well as genes involved in neurodegenerative disorders. Therefore, dysfunction of genes involved in signaling pathways associated with neurodegenerative disorders, ribosome function and protein translation may contribute to the pathogenesis of TOF

  18. Screening possible solid electrolytes by calculating the conduction pathways using Bond Valence method

    Science.gov (United States)

    Gao, Jian; Chu, Geng; He, Meng; Zhang, Shu; Xiao, RuiJuan; Li, Hong; Chen, LiQuan

    2014-08-01

    Inorganic solid electrolytes have distinguished advantages in terms of safety and stability, and are promising to substitute for conventional organic liquid electrolytes. However, low ionic conductivity of typical candidates is the key problem. As connective diffusion path is the prerequisite for high performance, we screen for possible solid electrolytes from the 2004 International Centre for Diffraction Data (ICDD) database by calculating conduction pathways using Bond Valence (BV) method. There are 109846 inorganic crystals in the 2004 ICDD database, and 5295 of them contain lithium. Except for those with toxic, radioactive, rare, or variable valence elements, 1380 materials are candidates for solid electrolytes. The rationality of the BV method is approved by comparing the existing solid electrolytes' conduction pathways we had calculated with those from experiments or first principle calculations. The implication for doping and substitution, two important ways to improve the conductivity, is also discussed. Among them Li2CO3 is selected for a detailed comparison, and the pathway is reproduced well with that based on the density functional studies. To reveal the correlation between connectivity of pathways and conductivity, α/ γ-LiAlO2 and Li2CO3 are investigated by the impedance spectrum as an example, and many experimental and theoretical studies are in process to indicate the relationship between property and structure. The BV method can calculate one material within a few minutes, providing an efficient way to lock onto targets from abundant data, and to investigate the structure-property relationship systematically.

  19. Integrated bioinformatic analysis unveils significant genes and pathways in the pathogenesis of supratentorial primitive neuroectodermal tumor

    Directory of Open Access Journals (Sweden)

    Wang G

    2018-04-01

    Full Text Available Guang-Yu Wang,1,* Ling Li,2,* Bo Liu,1 Xiao Han,1 Chun-Hua Wang,1 Ji-Wen Wang3 1Department of Neurosurgery, 2Department of Pediatrics, Qilu Children’s Hospital of Shandong University, Jinan, Shandong, 3Department of Neurology, Shanghai Children’s Medical Center, Shanghai Jiaotong University School of Medicine, Pudong New District, Shanghai, People’s Republic of China *These authors contributed equally to this work Purpose: This study aimed to explore significant genes and pathways involved in the pathogenesis of supratentorial primitive neuroectodermal tumor (sPNET. Materials and methods: Gene expression profile of GSE14295 was downloaded from publicly available Gene Expression Omnibus (GEO database. Differentially expressed genes (DEGs were screened out in primary sPNET samples compared with normal fetal and adult brain reference samples (sPNET vs fetal brain and sPNET vs adult brain. Pathway enrichment analysis of these DEGs was conducted, followed by protein–protein interaction (PPI network construction and significant module selection. Additionally, transcription factors (TFs regulating the common DEGs in the two comparison groups were identified, and the regulatory network was constructed. Results: In total, 526 DEGs (99 up- and 427 downregulated in sPNET vs fetal brain and 815 DEGs (200 up- and 615 downregulated in sPNET vs adult brain were identified. DEGs in sPNET vs fetal brain and sPNET vs adult brain were associated with calcium signaling pathway, cell cycle, and p53 signaling pathway. CDK1, CDC20, BUB1B, and BUB1 were hub nodes in the PPI networks of DEGs in sPNET vs fetal brain and sPNET vs adult brain. Significant modules were extracted from the PPI networks. In addition, 64 upregulated and 200 downregulated overlapping DEGs were identified in both sPNET vs fetal brain and sPNET vs adult brain. The genes involved in the regulatory network upon overlapping DEGs and the TFs were correlated with calcium signaling pathway

  20. Modelling and performance analysis of clinical pathways using the stochastic process algebra PEPA.

    Science.gov (United States)

    Yang, Xian; Han, Rui; Guo, Yike; Bradley, Jeremy; Cox, Benita; Dickinson, Robert; Kitney, Richard

    2012-01-01

    Hospitals nowadays have to serve numerous patients with limited medical staff and equipment while maintaining healthcare quality. Clinical pathway informatics is regarded as an efficient way to solve a series of hospital challenges. To date, conventional research lacks a mathematical model to describe clinical pathways. Existing vague descriptions cannot fully capture the complexities accurately in clinical pathways and hinders the effective management and further optimization of clinical pathways. Given this motivation, this paper presents a clinical pathway management platform, the Imperial Clinical Pathway Analyzer (ICPA). By extending the stochastic model performance evaluation process algebra (PEPA), ICPA introduces a clinical-pathway-specific model: clinical pathway PEPA (CPP). ICPA can simulate stochastic behaviours of a clinical pathway by extracting information from public clinical databases and other related documents using CPP. Thus, the performance of this clinical pathway, including its throughput, resource utilisation and passage time can be quantitatively analysed. A typical clinical pathway on stroke extracted from a UK hospital is used to illustrate the effectiveness of ICPA. Three application scenarios are tested using ICPA: 1) redundant resources are identified and removed, thus the number of patients being served is maintained with less cost; 2) the patient passage time is estimated, providing the likelihood that patients can leave hospital within a specific period; 3) the maximum number of input patients are found, helping hospitals to decide whether they can serve more patients with the existing resource allocation. ICPA is an effective platform for clinical pathway management: 1) ICPA can describe a variety of components (state, activity, resource and constraints) in a clinical pathway, thus facilitating the proper understanding of complexities involved in it; 2) ICPA supports the performance analysis of clinical pathway, thereby assisting

  1. Network Expansion and Pathway Enrichment Analysis towards Biologically Significant Findings from Microarrays

    Directory of Open Access Journals (Sweden)

    Wu Xiaogang

    2012-06-01

    Full Text Available In many cases, crucial genes show relatively slight changes between groups of samples (e.g. normal vs. disease, and many genes selected from microarray differential analysis by measuring the expression level statistically are also poorly annotated and lack of biological significance. In this paper, we present an innovative approach - network expansion and pathway enrichment analysis (NEPEA for integrative microarray analysis. We assume that organized knowledge will help microarray data analysis in significant ways, and the organized knowledge could be represented as molecular interaction networks or biological pathways. Based on this hypothesis, we develop the NEPEA framework based on network expansion from the human annotated and predicted protein interaction (HAPPI database, and pathway enrichment from the human pathway database (HPD. We use a recently-published microarray dataset (GSE24215 related to insulin resistance and type 2 diabetes (T2D as case study, since this study provided a thorough experimental validation for both genes and pathways identified computationally from classical microarray analysis and pathway analysis. We perform our NEPEA analysis for this dataset based on the results from the classical microarray analysis to identify biologically significant genes and pathways. Our findings are not only consistent with the original findings mostly, but also obtained more supports from other literatures.

  2. Literature mining, gene-set enrichment and pathway analysis for target identification in Behçet's disease.

    Science.gov (United States)

    Wilson, Paul; Larminie, Christopher; Smith, Rona

    2016-01-01

    To use literature mining to catalogue Behçet's associated genes, and advanced computational methods to improve the understanding of the pathways and signalling mechanisms that lead to the typical clinical characteristics of Behçet's patients. To extend this technique to identify potential treatment targets for further experimental validation. Text mining methods combined with gene enrichment tools, pathway analysis and causal analysis algorithms. This approach identified 247 human genes associated with Behçet's disease and the resulting disease map, comprising 644 nodes and 19220 edges, captured important details of the relationships between these genes and their associated pathways, as described in diverse data repositories. Pathway analysis has identified how Behçet's associated genes are likely to participate in innate and adaptive immune responses. Causal analysis algorithms have identified a number of potential therapeutic strategies for further investigation. Computational methods have captured pertinent features of the prominent disease characteristics presented in Behçet's disease and have highlighted NOD2, ICOS and IL18 signalling as potential therapeutic strategies.

  3. Data Analysis Methods for Paleogenomics

    DEFF Research Database (Denmark)

    Avila Arcos, Maria del Carmen

    (Danmarks Grundforskningfond) 'Centre of Excellence in GeoGenetics' grant, with additional funding provided by the Danish Council for Independent Research 'Sapere Aude' programme. The thesis comprises five chapters, all of which represent different projects that involved the analysis of massive amounts......, thanks to the introduction of NGS and the implementation of data analysis methods specific for each project. Chapters 1 to 3 have been published in peer-reviewed journals and Chapter 4 is currently in review. Chapter 5 consists of a manuscript describing initial results of an ongoing research project......The work presented in this thesis is the result of research carried out during a three-year PhD at the Centre for GeoGenetics, Natural History Museum of Denmark, University of Copenhagen, under supervision of Professor Tom Gilbert. The PhD was funded by the Danish National Research Foundation...

  4. Pathway analysis for identification of potential biomarkers in severe ...

    African Journals Online (AJOL)

    It was found by geneMANIA database search that majority of these genes were coexpressed yielding 84.63 % co-expression. It was found that ten genes were in Physical interactions comprising almost 14.33 %. There were < 1 % pathway and genetic interactions with values of 0.97 and 0.06 %, respectively. Final analyses ...

  5. Analysis of Chlorogenic Acid Oxidation Pathway in Simulated ...

    African Journals Online (AJOL)

    Keywords: Honeysuckle, Chlorogenic acid, Enzymatic browning, Mimic system, Oxidation pathway, ... enzymatic oxidation of CA is the major cause of ..... to the concentration of catechol, o-quinone and current at PPO-modified microcylinder biosensor for diffusion- kinetic model. J Electroanal Chem 2011; 660: 200-208.

  6. A New Boron Analysis Method

    Energy Technology Data Exchange (ETDEWEB)

    Weitman, J; Daaverhoeg, N; Farvolden, S

    1970-07-01

    In connection with fast neutron (n, {alpha}) cross section measurements a novel boron analysis method has been developed. The boron concentration is inferred from the mass spectrometrically determined number of helium atoms produced in the thermal and epithermal B-10 (n, {alpha}) reaction. The relation between helium amount and boron concentration is given, including corrections for self shielding effects and background levels. Direct and diffusion losses of helium are calculated and losses due to gettering, adsorption and HF-ionization in the release stage are discussed. A series of boron determinations is described and the results are compared with those obtained by other methods, showing excellent agreement. The lower limit of boron concentration which can be measured varies with type of sample. In e.g. steel, concentrations below 10-5 % boron in samples of 0.1-1 gram may be determined.

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

    Science.gov (United States)

    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

  8. PathNet: A Tool for Pathway Analysis Using Topological Information

    Science.gov (United States)

    2012-09-24

    potentiation (4720) 0.00 [31,32] 4 Neurotrophin signal. . . (4722) 0.01 [31,48] 4 Oocyte meiosis (4114) 0.00 NA 4 Pathways in cancer (5200) 0.71 [35-37...McKeel D, Morris JC, et al: Gene expression profiles in anatomically and functionally distinct regions of the normal aged human brain. Physiol...Background: Identification of canonical pathways through enrichment of differentially expressed genes in a given pathway is a widely used method for

  9. Pan-cancer analysis of TCGA data reveals notable signaling pathways

    International Nuclear Information System (INIS)

    Neapolitan, Richard; Horvath, Curt M.; Jiang, Xia

    2015-01-01

    A signal transduction pathway (STP) is a network of intercellular information flow initiated when extracellular signaling molecules bind to cell-surface receptors. Many aberrant STPs have been associated with various cancers. To develop optimal treatments for cancer patients, it is important to discover which STPs are implicated in a cancer or cancer-subtype. The Cancer Genome Atlas (TCGA) makes available gene expression level data on cases and controls in ten different types of cancer including breast cancer, colon adenocarcinoma, glioblastoma, kidney renal papillary cell carcinoma, low grade glioma, lung adenocarcinoma, lung squamous cell carcinoma, ovarian carcinoma, rectum adenocarcinoma, and uterine corpus endometriod carcinoma. Signaling Pathway Impact Analysis (SPIA) is a software package that analyzes gene expression data to identify whether a pathway is relevant in a given condition. We present the results of a study that uses SPIA to investigate all 157 signaling pathways in the KEGG PATHWAY database. We analyzed each of the ten cancer types mentioned above separately, and we perform a pan-cancer analysis by grouping the data for all the cancer types. In each analysis several pathways were found to be markedly more significant than all the other pathways. We call them notable. Research has already established a connection between many of these pathways and the corresponding cancer type. However, some of our discovered pathways appear to be new findings. Altogether there were 37 notable findings in the separate analyses, 26 of them occurred in 7 pathways. These 7 pathways included the 4 notable pathways discovered in the pan-cancer analysis. So, our results suggest that these 7 pathways account for much of the mechanisms of cancer. Furthermore, by looking at the overlap among pathways, we identified possible regions on the pathways where the aberrant activity is occurring. We obtained 37 notable findings concerning 18 pathways. Some of them appear to be

  10. Inference of miRNA targets using evolutionary conservation and pathway analysis

    Directory of Open Access Journals (Sweden)

    van Nimwegen Erik

    2007-03-01

    assigns a posterior probability to each putative target site. The results presented here indicate that our general method achieves very good performance in predicting miRNA target sites, providing at the same time insights into the evolution of target sites for individual miRNAs. Moreover, by combining our predictions with pathway analysis, we propose functions of specific miRNAs in nervous system development, inter-cellular communication and cell growth. The complete target site predictions as well as the miRNA/pathway associations are accessible on the ElMMo web server.

  11. COMPETITIVE INTELLIGENCE ANALYSIS - SCENARIOS METHOD

    Directory of Open Access Journals (Sweden)

    Ivan Valeriu

    2014-07-01

    Full Text Available Keeping a company in the top performing players in the relevant market depends not only on its ability to develop continually, sustainably and balanced, to the standards set by the customer and competition, but also on the ability to protect its strategic information and to know in advance the strategic information of the competition. In addition, given that economic markets, regardless of their profile, enable interconnection not only among domestic companies, but also between domestic companies and foreign companies, the issue of economic competition moves from the national economies to the field of interest of regional and international economic organizations. The stakes for each economic player is to keep ahead of the competition and to be always prepared to face market challenges. Therefore, it needs to know as early as possible, how to react to others’ strategy in terms of research, production and sales. If a competitor is planning to produce more and cheaper, then it must be prepared to counteract quickly this movement. Competitive intelligence helps to evaluate the capabilities of competitors in the market, legally and ethically, and to develop response strategies. One of the main goals of the competitive intelligence is to acknowledge the role of early warning and prevention of surprises that could have a major impact on the market share, reputation, turnover and profitability in the medium and long term of a company. This paper presents some aspects of competitive intelligence, mainly in terms of information analysis and intelligence generation. Presentation is theoretical and addresses a structured method of information analysis - scenarios method – in a version that combines several types of analysis in order to reveal some interconnecting aspects of the factors governing the activity of a company.

  12. Genome-Wide Gene Set Analysis for Identification of Pathways Associated with Alcohol Dependence

    Science.gov (United States)

    Biernacka, Joanna M.; Geske, Jennifer; Jenkins, Gregory D.; Colby, Colin; Rider, David N.; Karpyak, Victor M.; Choi, Doo-Sup; Fridley, Brooke L.

    2013-01-01

    It is believed that multiple genetic variants with small individual effects contribute to the risk of alcohol dependence. Such polygenic effects are difficult to detect in genome-wide association studies that test for association of the phenotype with each single nucleotide polymorphism (SNP) individually. To overcome this challenge, gene set analysis (GSA) methods that jointly test for the effects of pre-defined groups of genes have been proposed. Rather than testing for association between the phenotype and individual SNPs, these analyses evaluate the global evidence of association with a set of related genes enabling the identification of cellular or molecular pathways or biological processes that play a role in development of the disease. It is hoped that by aggregating the evidence of association for all available SNPs in a group of related genes, these approaches will have enhanced power to detect genetic associations with complex traits. We performed GSA using data from a genome-wide study of 1165 alcohol dependent cases and 1379 controls from the Study of Addiction: Genetics and Environment (SAGE), for all 200 pathways listed in the Kyoto Encyclopedia of Genes and Genomes (KEGG) database. Results demonstrated a potential role of the “Synthesis and Degradation of Ketone Bodies” pathway. Our results also support the potential involvement of the “Neuroactive Ligand Receptor Interaction” pathway, which has previously been implicated in addictive disorders. These findings demonstrate the utility of GSA in the study of complex disease, and suggest specific directions for further research into the genetic architecture of alcohol dependence. PMID:22717047

  13. Investigating a multigene prognostic assay based on significant pathways for Luminal A breast cancer through gene expression profile analysis.

    Science.gov (United States)

    Gao, Haiyan; Yang, Mei; Zhang, Xiaolan

    2018-04-01

    The present study aimed to investigate potential recurrence-risk biomarkers based on significant pathways for Luminal A breast cancer through gene expression profile analysis. Initially, the gene expression profiles of Luminal A breast cancer patients were downloaded from The Cancer Genome Atlas database. The differentially expressed genes (DEGs) were identified using a Limma package and the hierarchical clustering analysis was conducted for the DEGs. In addition, the functional pathways were screened using Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses and rank ratio calculation. The multigene prognostic assay was exploited based on the statistically significant pathways and its prognostic function was tested using train set and verified using the gene expression data and survival data of Luminal A breast cancer patients downloaded from the Gene Expression Omnibus. A total of 300 DEGs were identified between good and poor outcome groups, including 176 upregulated genes and 124 downregulated genes. The DEGs may be used to effectively distinguish Luminal A samples with different prognoses verified by hierarchical clustering analysis. There were 9 pathways screened as significant pathways and a total of 18 DEGs involved in these 9 pathways were identified as prognostic biomarkers. According to the survival analysis and receiver operating characteristic curve, the obtained 18-gene prognostic assay exhibited good prognostic function with high sensitivity and specificity to both the train and test samples. In conclusion the 18-gene prognostic assay including the key genes, transcription factor 7-like 2, anterior parietal cortex and lymphocyte enhancer factor-1 may provide a new method for predicting outcomes and may be conducive to the promotion of precision medicine for Luminal A breast cancer.

  14. Exploring the Leishmania Hydrophilic Acylated Surface Protein B (HASPB) Export Pathway by Live Cell Imaging Methods.

    Science.gov (United States)

    MacLean, Lorna; Price, Helen; O'Toole, Peter

    2016-01-01

    Leishmania major is a human-infective protozoan parasite transmitted by the bite of the female phlebotomine sand fly. The L. major hydrophilic acylated surface protein B (HASPB) is only expressed in infective parasite stages suggesting a role in parasite virulence. HASPB is a "nonclassically" secreted protein that lacks a conventional signal peptide, reaching the cell surface by an alternative route to the classical ER-Golgi pathway. Instead HASPB trafficking to and exposure on the parasite plasma membrane requires dual N-terminal acylation. Here, we use live cell imaging methods to further explore this pathway allowing visualization of key events in real time at the individual cell level. These methods include live cell imaging using fluorescent reporters to determine the subcellular localization of wild type and acylation site mutation HASPB18-GFP fusion proteins, fluorescence recovery after photobleaching (FRAP) to analyze the dynamics of HASPB in live cells, and live antibody staining to detect surface exposure of HASPB by confocal microscopy.

  15. Disease-specific clinical pathways - are they feasible in primary care? A mixed-methods study.

    Science.gov (United States)

    Grimsmo, Anders; Løhre, Audhild; Røsstad, Tove; Gjerde, Ingunn; Heiberg, Ina; Steinsbekk, Aslak

    2018-04-12

    To explore the feasibility of disease-specific clinical pathways when used in primary care. A mixed-method sequential exploratory design was used. First, merging and exploring quality interview data across two cases of collaboration between the specialist care and primary care on the introduction of clinical pathways for four selected chronic diseases. Secondly, using quantitative data covering a population of 214,700 to validate and test hypothesis derived from the qualitative findings. Primary care and specialist care collaborating to manage care coordination. Primary-care representatives expressed that their patients often have complex health and social needs that clinical pathways guidelines seldom consider. The representatives experienced that COPD, heart failure, stroke and hip fracture, frequently seen in hospitals, appear in low numbers in primary care. The quantitative study confirmed the extensive complexity among home healthcare nursing patients and demonstrated that, for each of the four selected diagnoses, a homecare nurse on average is responsible for preparing reception of the patient at home after discharge from hospital, less often than every other year. The feasibility of disease-specific pathways in primary care is limited, both from a clinical and organisational perspective, for patients with complex needs. The low prevalence in primary care of patients with important chronic conditions, needing coordinated care after hospital discharge, constricts transferring tasks from specialist care. Generic clinical pathways are likely to be more feasible and efficient for patients in this setting. Key points Clinical pathways in hospitals apply to single-disease guidelines, while more than 90% of the patients discharged to community health care for follow-up have multimorbidity. Primary care has to manage the health care of the patient holistically, with all his or her complex needs. Patients most frequently admitted to hospitals, i.e. patients with COPD

  16. Gravimetric and titrimetric methods of analysis

    International Nuclear Information System (INIS)

    Rives, R.D.; Bruks, R.R.

    1983-01-01

    Gravimetric and titrimetric methods of analysis are considered. Methods of complexometric titration are mentioned, as well as methods of increasing sensitivity in titrimetry. Gravimetry and titrimetry are applied during analysis for traces of geological materials

  17. The combination of four analytical methods to explore skeletal muscle metabolomics: Better coverage of metabolic pathways or a marketing argument?

    Science.gov (United States)

    Bruno, C; Patin, F; Bocca, C; Nadal-Desbarats, L; Bonnier, F; Reynier, P; Emond, P; Vourc'h, P; Joseph-Delafont, K; Corcia, P; Andres, C R; Blasco, H

    2018-01-30

    Metabolomics is an emerging science based on diverse high throughput methods that are rapidly evolving to improve metabolic coverage of biological fluids and tissues. Technical progress has led researchers to combine several analytical methods without reporting the impact on metabolic coverage of such a strategy. The objective of our study was to develop and validate several analytical techniques (mass spectrometry coupled to gas or liquid chromatography and nuclear magnetic resonance) for the metabolomic analysis of small muscle samples and evaluate the impact of combining methods for more exhaustive metabolite covering. We evaluated the muscle metabolome from the same pool of mouse muscle samples after 2 metabolite extraction protocols. Four analytical methods were used: targeted flow injection analysis coupled with mass spectrometry (FIA-MS/MS), gas chromatography coupled with mass spectrometry (GC-MS), liquid chromatography coupled with high-resolution mass spectrometry (LC-HRMS), and nuclear magnetic resonance (NMR) analysis. We evaluated the global variability of each compound i.e., analytical (from quality controls) and extraction variability (from muscle extracts). We determined the best extraction method and we reported the common and distinct metabolites identified based on the number and identity of the compounds detected with low analytical variability (variation coefficient<30%) for each method. Finally, we assessed the coverage of muscle metabolic pathways obtained. Methanol/chloroform/water and water/methanol were the best extraction solvent for muscle metabolome analysis by NMR and MS, respectively. We identified 38 metabolites by nuclear magnetic resonance, 37 by FIA-MS/MS, 18 by GC-MS, and 80 by LC-HRMS. The combination led us to identify a total of 132 metabolites with low variability partitioned into 58 metabolic pathways, such as amino acid, nitrogen, purine, and pyrimidine metabolism, and the citric acid cycle. This combination also showed

  18. Identification of differentially expressed genes and signaling pathways in ovarian cancer by integrated bioinformatics analysis

    Directory of Open Access Journals (Sweden)

    Yang X

    2018-03-01

    Full Text Available Xiao Yang,1 Shaoming Zhu,2 Li Li,3 Li Zhang,1 Shu Xian,1 Yanqing Wang,1 Yanxiang Cheng1 1Department of Obstetrics and Gynecology, 2Department of Urology, Renmin Hospital of Wuhan University, 3Department of Pharmacology, Wuhan University Health Science Center, Wuhan, Hubei, People’s Republic of China Background: The mortality rate associated with ovarian cancer ranks the highest among gynecological malignancies. However, the cause and underlying molecular events of ovarian cancer are not clear. Here, we applied integrated bioinformatics to identify key pathogenic genes involved in ovarian cancer and reveal potential molecular mechanisms. Results: The expression profiles of GDS3592, GSE54388, and GSE66957 were downloaded from the Gene Expression Omnibus (GEO database, which contained 115 samples, including 85 cases of ovarian cancer samples and 30 cases of normal ovarian samples. The three microarray datasets were integrated to obtain differentially expressed genes (DEGs and were deeply analyzed by bioinformatics methods. The gene ontology (GO and Kyoto Encyclopedia of Genes and Genomes (KEGG pathway enrichments of DEGs were performed by DAVID and KOBAS online analyses, respectively. The protein–protein interaction (PPI networks of the DEGs were constructed from the STRING database. A total of 190 DEGs were identified in the three GEO datasets, of which 99 genes were upregulated and 91 genes were downregulated. GO analysis showed that the biological functions of DEGs focused primarily on regulating cell proliferation, adhesion, and differentiation and intracellular signal cascades. The main cellular components include cell membranes, exosomes, the cytoskeleton, and the extracellular matrix. The molecular functions include growth factor activity, protein kinase regulation, DNA binding, and oxygen transport activity. KEGG pathway analysis showed that these DEGs were mainly involved in the Wnt signaling pathway, amino acid metabolism, and the

  19. The Use of Gene Ontology Term and KEGG Pathway Enrichment for Analysis of Drug Half-Life.

    Directory of Open Access Journals (Sweden)

    Yu-Hang Zhang

    Full Text Available A drug's biological half-life is defined as the time required for the human body to metabolize or eliminate 50% of the initial drug dosage. Correctly measuring the half-life of a given drug is helpful for the safe and accurate usage of the drug. In this study, we investigated which gene ontology (GO terms and biological pathways were highly related to the determination of drug half-life. The investigated drugs, with known half-lives, were analyzed based on their enrichment scores for associated GO terms and KEGG pathways. These scores indicate which GO terms or KEGG pathways the drug targets. The feature selection method, minimum redundancy maximum relevance, was used to analyze these GO terms and KEGG pathways and to identify important GO terms and pathways, such as sodium-independent organic anion transmembrane transporter activity (GO:0015347, monoamine transmembrane transporter activity (GO:0008504, negative regulation of synaptic transmission (GO:0050805, neuroactive ligand-receptor interaction (hsa04080, serotonergic synapse (hsa04726, and linoleic acid metabolism (hsa00591, among others. This analysis confirmed our results and may show evidence for a new method in studying drug half-lives and building effective computational methods for the prediction of drug half-lives.

  20. Linked Analysis of East Asia Emission Reduction Pathways

    Science.gov (United States)

    Kim, Y.; Woo, J. H.; Bu, C.; Lee, Y.; Kim, J.; Jang, Y.; Park, M.

    2017-12-01

    Air pollution and its impacts over the Northeast Asia are very severe because of the massive pollutant emissions and high population. Korea has been trying to improve air quality with the enhanced environmental legislation. The air quality over Korea, however, does not entirely dependent on its local emissions. Transboundary air pollution from China highly affects Korean atmosphere. The purpose of this research is to understand role of local and transbounday efforts to improve air quality changes over Korea. In this research, we have tried to set up the multiple emission scenario pathways for Korea and China using IIASA's GAINS (Greenhouse gas - Air pollution Interactions aNd Synergies) modeling framework. More up-to-date growth factors and control policy packets were made using regional socio-economic data and control policy information from local governments and international statistics. Four major scenario pathways, 1) Base (Baseline: current legislation), 2) OTB/OTB(On the book/On the way : existing control measure/planed control measure), 3) BOTW_GHG(Beyond on the way : OTW with GHG reduction plan), 4) BOTW_NH3 (OTW with additional NH3 reduction measure) were developed to represent air quality improvement pathways in consideration of both Korean and Chinese efforts. Strict ambient PM2.5 standards from Seoul metropolitan Air quality Improvement Plan(SAIP) seems too enthusiastic without linking air quality control efforts of China. Step-by-step emission controls and following air quality, control cost, health impact from each scenario will be presented at the conference. This subject is supported by Korea Ministry of Environment as "Climate Change Correspondence Program". And This work was supported under the framework of national strategy project on fine particulate matters by Ministry of Science, ICT and Future Planning.

  1. Gene prediction validation and functional analysis of redundant pathways

    DEFF Research Database (Denmark)

    Sønderkær, Mads

    2011-01-01

    have employed a large mRNA-seq data set to improve and validate ab initio predicted gene models. This direct experimental evidence also provides reliable determinations of UTR regions and polyadenylation sites, which are not easily predicted in plants. Furthermore, once an annotated genome sequence...... is available, gene expression by mRNA-Seq enables acquisition of a more complete overview of gene isoform usage in complex enzymatic pathways enabling the identification of key genes. Metabolism in potatoes This information is useful e.g. for crop improvement based on manipulation of agronomically important...

  2. New force replica exchange method and protein folding pathways probed by force-clamp technique.

    Science.gov (United States)

    Kouza, Maksim; Hu, Chin-Kun; Li, Mai Suan

    2008-01-28

    We have developed a new extended replica exchange method to study thermodynamics of a system in the presence of external force. Our idea is based on the exchange between different force replicas to accelerate the equilibrium process. This new approach was applied to obtain the force-temperature phase diagram and other thermodynamical quantities of the three-domain ubiquitin. Using the C(alpha)-Go model and the Langevin dynamics, we have shown that the refolding pathways of single ubiquitin depend on which terminus is fixed. If the N end is fixed then the folding pathways are different compared to the case when both termini are free, but fixing the C terminal does not change them. Surprisingly, we have found that the anchoring terminal does not affect the pathways of individual secondary structures of three-domain ubiquitin, indicating the important role of the multidomain construction. Therefore, force-clamp experiments, in which one end of a protein is kept fixed, can probe the refolding pathways of a single free-end ubiquitin if one uses either the polyubiquitin or a single domain with the C terminus anchored. However, it is shown that anchoring one end does not affect refolding pathways of the titin domain I27, and the force-clamp spectroscopy is always capable to predict folding sequencing of this protein. We have obtained the reasonable estimate for unfolding barrier of ubiquitin, using the microscopic theory for the dependence of unfolding time on the external force. The linkage between residue Lys48 and the C terminal of ubiquitin is found to have the dramatic effect on the location of the transition state along the end-to-end distance reaction coordinate, but the multidomain construction leaves the transition state almost unchanged. We have found that the maximum force in the force-extension profile from constant velocity force pulling simulations depends on temperature nonlinearly. However, for some narrow temperature interval this dependence becomes

  3. Pathway-based analysis of a melanoma genome-wide association study: analysis of genes related to tumour-immunosuppression.

    Directory of Open Access Journals (Sweden)

    Nils Schoof

    Full Text Available 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 (p(emp=0.002, as well as the subgroups related to the generation of tolerogenic dendritic cells (p(emp=0.006 and secretion of suppressive factors (p(emp=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.

  4. Proteomic Analysis of Hylocereus polyrhizus Reveals Metabolic Pathway Changes

    Directory of Open Access Journals (Sweden)

    Qingzhu Hua

    2016-09-01

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

  5. Pathway Analysis and Metabolites Identification by Metabolomics of Etiolation Substrate from Fresh-Cut Chinese Water Chestnut (Eleocharis tuberosa

    Directory of Open Access Journals (Sweden)

    Yi-Xiao Li

    2016-12-01

    Full Text Available Fresh-cut Chinese water chestnuts (CWC turn yellow after being peeled, reducing their shelf life and commercial value. Metabolomics, the systematic study of the full complement of small molecular metabolites, was useful for clarifying the mechanism of fresh-cut CWC etiolation and developing methods to inhibit yellowing. In this study, metabolic alterations associated with etiolation at different growth stages (0 day, 2 days, 3 days, 4 days, 5 days from fresh-cut CWC were investigated using LC–MS and analyzed by pattern recognition methods (principal component analysis (PCA, partial least squares-discriminant analysis (PLS-DA, and orthogonal projection to latent structures-discriminant analysis (OPLS-DA. The metabolic pathways of the etiolation molecules were elucidated. The main metabolic pathway appears to be the conversion of phenylalanine to p-coumaroyl-CoA, followed by conversion to naringenin chalcone, to naringenin, and naringenin then following different pathways. Firstly, it can transform into apigenin and its derivatives; secondly, it can produce eriodictyol and its derivatives; and thirdly it can produce dihydrokaempferol, quercetin, and myricetin. The eriodictyol can be further transformed to luteolin, cyanidin, dihydroquercetin, dihydrotricetin, and others. This is the first reported use of metabolomics to study the metabolic pathways of the etiolation of fresh-cut CWC.

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

    Energy Technology Data Exchange (ETDEWEB)

    Jannik, Tim [Savannah River Site (SRS), Aiken, SC (United States). Savannah River National Lab. (SRNL); Hartman, Larry [Savannah River Site (SRS), Aiken, SC (United States). Savannah River National Lab. (SRNL)

    2016-09-08

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

  7. GenMAPP 2: new features and resources for pathway analysis

    Directory of Open Access Journals (Sweden)

    Dahlquist Kam D

    2007-06-01

    Full Text Available Abstract Background Microarray technologies have evolved rapidly, enabling biologists to quantify genome-wide levels of gene expression, alternative splicing, and sequence variations for a variety of species. Analyzing and displaying these data present a significant challenge. Pathway-based approaches for analyzing microarray data have proven useful for presenting data and for generating testable hypotheses. Results To address the growing needs of the microarray community we have released version 2 of Gene Map Annotator and Pathway Profiler (GenMAPP, a new GenMAPP database schema, and integrated resources for pathway analysis. We have redesigned the GenMAPP database to support multiple gene annotations and species as well as custom species database creation for a potentially unlimited number of species. We have expanded our pathway resources by utilizing homology information to translate pathway content between species and extending existing pathways with data derived from conserved protein interactions and coexpression. We have implemented a new mode of data visualization to support analysis of complex data, including time-course, single nucleotide polymorphism (SNP, and splicing. GenMAPP version 2 also offers innovative ways to display and share data by incorporating HTML export of analyses for entire sets of pathways as organized web pages. Conclusion GenMAPP version 2 provides a means to rapidly interrogate complex experimental data for pathway-level changes in a diverse range of organisms.

  8. Analysis methods (from 301 to 351)

    International Nuclear Information System (INIS)

    Analysis methods of materials used in the nuclear field (uranium, plutonium and their compounds, zirconium, magnesium, water...) and determination of impurities. Only reliable methods are selected [fr

  9. From elementary flux modes to elementary flux vectors: Metabolic pathway analysis with arbitrary linear flux constraints

    Science.gov (United States)

    Klamt, Steffen; Gerstl, Matthias P.; Jungreuthmayer, Christian; Mahadevan, Radhakrishnan; Müller, Stefan

    2017-01-01

    Elementary flux modes (EFMs) emerged as a formal concept to describe metabolic pathways and have become an established tool for constraint-based modeling and metabolic network analysis. EFMs are characteristic (support-minimal) vectors of the flux cone that contains all feasible steady-state flux vectors of a given metabolic network. EFMs account for (homogeneous) linear constraints arising from reaction irreversibilities and the assumption of steady state; however, other (inhomogeneous) linear constraints, such as minimal and maximal reaction rates frequently used by other constraint-based techniques (such as flux balance analysis [FBA]), cannot be directly integrated. These additional constraints further restrict the space of feasible flux vectors and turn the flux cone into a general flux polyhedron in which the concept of EFMs is not directly applicable anymore. For this reason, there has been a conceptual gap between EFM-based (pathway) analysis methods and linear optimization (FBA) techniques, as they operate on different geometric objects. One approach to overcome these limitations was proposed ten years ago and is based on the concept of elementary flux vectors (EFVs). Only recently has the community started to recognize the potential of EFVs for metabolic network analysis. In fact, EFVs exactly represent the conceptual development required to generalize the idea of EFMs from flux cones to flux polyhedra. This work aims to present a concise theoretical and practical introduction to EFVs that is accessible to a broad audience. We highlight the close relationship between EFMs and EFVs and demonstrate that almost all applications of EFMs (in flux cones) are possible for EFVs (in flux polyhedra) as well. In fact, certain properties can only be studied with EFVs. Thus, we conclude that EFVs provide a powerful and unifying framework for constraint-based modeling of metabolic networks. PMID:28406903

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

    Science.gov (United States)

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

    2013-01-01

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

  11. Investigating multiple dysregulated pathways in rheumatoid arthritis based on pathway interaction network.

    Science.gov (United States)

    Song, Xian-Dong; Song, Xian-Xu; Liu, Gui-Bo; Ren, Chun-Hui; Sun, Yuan-Bo; Liu, Ke-Xin; Liu, Bo; Liang, Shuang; Zhu, Zhu

    2018-03-01

    The traditional methods of identifying biomarkers in rheumatoid arthritis (RA) have focussed on the differentially expressed pathways or individual pathways, which however, neglect the interactions between pathways. To better understand the pathogenesis of RA, we aimed to identify dysregulated pathway sets using a pathway interaction network (PIN), which considered interactions among pathways. Firstly, RA-related gene expression profile data, protein-protein interactions (PPI) data and pathway data were taken up from the corresponding databases. Secondly, principal component analysis method was used to calculate the pathway activity of each of the pathway, and then a seed pathway was identified using data gleaned from the pathway activity. A PIN was then constructed based on the gene expression profile, pathway data, and PPI information. Finally, the dysregulated pathways were extracted from the PIN based on the seed pathway using the method of support vector machines and an area under the curve (AUC) index. The PIN comprised of a total of 854 pathways and 1064 pathway interactions. The greatest change in the activity score between RA and control samples was observed in the pathway of epigenetic regulation of gene expression, which was extracted and regarded as the seed pathway. Starting with this seed pathway, one maximum pathway set containing 10 dysregulated pathways was extracted from the PIN, having an AUC of 0.8249, and the result indicated that this pathway set could distinguish RA from the controls. These 10 dysregulated pathways might be potential biomarkers for RA diagnosis and treatment in the future.

  12. An Evaluation of Active Learning Causal Discovery Methods for Reverse-Engineering Local Causal Pathways of Gene Regulation

    Science.gov (United States)

    Ma, Sisi; Kemmeren, Patrick; Aliferis, Constantin F.; Statnikov, Alexander

    2016-01-01

    Reverse-engineering of causal pathways that implicate diseases and vital cellular functions is a fundamental problem in biomedicine. Discovery of the local causal pathway of a target variable (that consists of its direct causes and direct effects) is essential for effective intervention and can facilitate accurate diagnosis and prognosis. Recent research has provided several active learning methods that can leverage passively observed high-throughput data to draft causal pathways and then refine the inferred relations with a limited number of experiments. The current study provides a comprehensive evaluation of the performance of active learning methods for local causal pathway discovery in real biological data. Specifically, 54 active learning methods/variants from 3 families of algorithms were applied for local causal pathways reconstruction of gene regulation for 5 transcription factors in S. cerevisiae. Four aspects of the methods’ performance were assessed, including adjacency discovery quality, edge orientation accuracy, complete pathway discovery quality, and experimental cost. The results of this study show that some methods provide significant performance benefits over others and therefore should be routinely used for local causal pathway discovery tasks. This study also demonstrates the feasibility of local causal pathway reconstruction in real biological systems with significant quality and low experimental cost. PMID:26939894

  13. DTI analysis methods : Voxel-based analysis

    NARCIS (Netherlands)

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

    2016-01-01

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

  14. Bayesian methods for data analysis

    CERN Document Server

    Carlin, Bradley P.

    2009-01-01

    Approaches for statistical inference Introduction Motivating Vignettes Defining the Approaches The Bayes-Frequentist Controversy Some Basic Bayesian Models The Bayes approach Introduction Prior Distributions Bayesian Inference Hierarchical Modeling Model Assessment Nonparametric Methods Bayesian computation Introduction Asymptotic Methods Noniterative Monte Carlo Methods Markov Chain Monte Carlo Methods Model criticism and selection Bayesian Modeling Bayesian Robustness Model Assessment Bayes Factors via Marginal Density Estimation Bayes Factors

  15. Substoichiometric method in the simple radiometric analysis

    International Nuclear Information System (INIS)

    Ikeda, N.; Noguchi, K.

    1979-01-01

    The substoichiometric method is applied to simple radiometric analysis. Two methods - the standard reagent method and the standard sample method - are proposed. The validity of the principle of the methods is verified experimentally in the determination of silver by the precipitation method, or of zinc by the ion-exchange or solvent-extraction method. The proposed methods are simple and rapid compared with the conventional superstoichiometric method. (author)

  16. Development of an open platform system for environmental pathway analysis

    International Nuclear Information System (INIS)

    LePoire, D. J.; Arnish, J. J.; Gnanapragasam, E.; Chen, S. Y.

    2001-01-01

    Most existing computer codes for environmental pathway modeling have been developed to satisfy a specific objective (e.g., perform analyses to demonstrate regulatory compliance). These codes were written in various computer languages and software environments over time and often are not mutually compatible. In recent years, largely driven by advancements in industrial software development, a new concept based on ''modularization'' has emerged. This approach entails the development of common ''modules,'' or components, that can be shared by and used in different applications that have certain common needs. For instance, an air dispersion model can be written as a common component to be shared by several different applications, each with the need to model air dispersion of some material release. When this concept is fully developed, modeling applications would become an exercise of selecting, integrating, and applying a consistent combination of appropriate pre-existing modules for a specific problem. Although modularization holds promising advantages over the traditional approach, a number of issues do exist. These issues must be fully addressed and resolved before the approach can be accepted as a new paradigm for environmental modeling. This paper discusses these issues and provides recommendations and a course of actions for future development

  17. Dose-volume complication analysis for visual pathway structures of patients with advanced paranasal sinus tumors

    International Nuclear Information System (INIS)

    Martel, Mary Kaye; Sandler, Howard M.; Cornblath, Wayne T.; Marsh, Lon H.; Hazuka, Mark B.; Roa, Wilson H.; Fraass, Benedict A.; Lichter, Allen S.

    1997-01-01

    Purpose: The purpose of the present work was to relate dose and volume information to complication data for visual pathway structures in patients with advanced paranasal sinus tumors. Methods and Materials: Three-dimensional (3D) dose distributions for chiasm, optic nerve, and retina were calculated and analyzed for 20 patients with advanced paranasal sinus malignant tumors. 3D treatment planning with beam's eye view capability was used to design beam and block arrangements, striving to spare the contralateral orbit (to lessen the chance of unilateral blindness) and frequently the ipsilateral orbit (to help prevent bilateral blindness). Point doses, dose-volume histogram analysis, and normal tissue complication probability (NTCP) calculations were performed. Published tolerance doses that indicate significant risk of complications were used as guidelines for analysis of the 3D dose distributions. Results: Point doses, percent volume exceeding a specified published tolerance dose, and NTCP calculations are given in detail for patients with complications versus patients without complications. Two optic nerves receiving maximum doses below the published tolerance dose sustained damage (mild vision loss). Three patients (of 13) without optic nerve sparing and/or chiasm sparing had moderate or severe vision loss. Complication data, including individual patient analysis to estimate overall risk for loss of vision, are given. Conclusion: 3D treatment planning techniques were used successfully to provide bilateral sparing of the globe for most patients. It was more difficult to spare the optic nerves, especially on the ipsilateral side, when prescription dose exceeded the normal tissue tolerance doses. NTCP calculations may be useful in assessing complication risk better than point dose tolerance criteria for the chiasm, optic nerve, and retina. It is important to assess the overall risk of blindness for the patient in addition to the risk for individual visual pathway

  18. Phase analysis in gated blood pool tomography. Detection of accessory conduction pathway

    Energy Technology Data Exchange (ETDEWEB)

    Nakajima, Kenichi; Bunko, Hisashi; Tada, Akira; Taki, Junichi; Nanbu, Ichiro (Kanazawa Univ. (Japan). School of Medicine)

    1984-02-01

    Phase analysis of gated blood pool study has been applied to detect the site of accessory conduction pathway (ACP) in the Wolff-Parkinson-White (WPW) syndrome; however, there was a limitation to detect the precise location of ACP by phase analysis alone. In this study, we applied phase analysis to gated blood pool tomography using seven pin hole tomography (7PT) and gated emission computed tomography (GECT) in 21 patients with WPW syndrome and 3 normal subjects. In 17 patients, the sites of ACPs were confirmed by epicardial mapping and the result of the surgical division of ACP. In 7PT, the site of ACP grossly agreed to the abnormal initial phase in phase image in 5 out of 6 patients with left cardiac type. In GECT, phase images were generated in short axial, vertical and horizontal long axial sections. In 8 out of 9 patients, the site of ACP was correctly identified by phase images, and in a patient who had two ACPs, initial phase corresponded to one of the two locations. Phase analysis of gated blood pool tomography has advantages for avoiding overlap of blood pools and for estimating three-dimensional propagation of the contraction, and can be a good adjunctive method in patients with WPW syndrome.

  19. Network Analysis Tools: from biological networks to clusters and pathways.

    Science.gov (United States)

    Brohée, Sylvain; Faust, Karoline; Lima-Mendez, Gipsi; Vanderstocken, Gilles; van Helden, Jacques

    2008-01-01

    Network Analysis Tools (NeAT) is a suite of computer tools that integrate various algorithms for the analysis of biological networks: comparison between graphs, between clusters, or between graphs and clusters; network randomization; analysis of degree distribution; network-based clustering and path finding. The tools are interconnected to enable a stepwise analysis of the network through a complete analytical workflow. In this protocol, we present a typical case of utilization, where the tasks above are combined to decipher a protein-protein interaction network retrieved from the STRING database. The results returned by NeAT are typically subnetworks, networks enriched with additional information (i.e., clusters or paths) or tables displaying statistics. Typical networks comprising several thousands of nodes and arcs can be analyzed within a few minutes. The complete protocol can be read and executed in approximately 1 h.

  20. Chemical methods of rock analysis

    National Research Council Canada - National Science Library

    Jeffery, P. G; Hutchison, D

    1981-01-01

    .... Such methods include those based upon spectrophotometry, flame emission spectrometry and atomic absorption spectroscopy, as well as gravimetry, titrimetry and the use of ion-selective electrodes...

  1. A Pathway-Centered Analysis of Pig Domestication and Breeding in Eurasia

    Directory of Open Access Journals (Sweden)

    Jordi Leno-Colorado

    2017-07-01

    Full Text Available Ascertaining the molecular and physiological basis of domestication and breeding is an active area of research. Due to the current wide distribution of its wild ancestor, the wild boar, the pig (Sus scrofa is an excellent model to study these processes, which occurred independently in East Asia and Europe ca. 9000 yr ago. Analyzing genome variability patterns in terms of metabolic pathways is attractive since it considers the impact of interrelated functions of genes, in contrast to genome-wide scans that treat genes or genome windows in isolation. To that end, we studied 40 wild boars and 123 domestic pig genomes from Asia and Europe when metabolic pathway was the unit of analysis. We computed statistical significance for differentiation (Fst and linkage disequilibrium (nSL statistics at the pathway level. In terms of Fst, we found 21 and 12 pathways significantly differentiated at a q-value 10 significant pathways (in terms of Fst, comprising genes involved in the transduction of a large number of signals, like phospholipase PCLB1, which is expressed in the brain, or ITPR3, which has an important role in taste transduction. In terms of nSL, significant pathways were mainly related to reproductive performance (ovarian steroidogenesis, a similarly important target trait during domestication and modern animal breeding. Different levels of recombination cannot explain these results, since we found no correlation between Fst and recombination rate. However, we did find an increased ratio of deleterious mutations in domestic vs. wild populations, suggesting a relaxed functional constraint associated with the domestication and breeding processes. Purifying selection was, nevertheless, stronger in significantly differentiated pathways than in random pathways, mainly in Europe. We conclude that pathway analysis facilitates the biological interpretation of genome-wide studies. Notably, in the case of pig, behavior played an important role, among other

  2. A Pathway-Centered Analysis of Pig Domestication and Breeding in Eurasia.

    Science.gov (United States)

    Leno-Colorado, Jordi; Hudson, Nick J; Reverter, Antonio; Pérez-Enciso, Miguel

    2017-07-05

    Ascertaining the molecular and physiological basis of domestication and breeding is an active area of research. Due to the current wide distribution of its wild ancestor, the wild boar, the pig ( Sus scrofa ) is an excellent model to study these processes, which occurred independently in East Asia and Europe ca. 9000 yr ago. Analyzing genome variability patterns in terms of metabolic pathways is attractive since it considers the impact of interrelated functions of genes, in contrast to genome-wide scans that treat genes or genome windows in isolation. To that end, we studied 40 wild boars and 123 domestic pig genomes from Asia and Europe when metabolic pathway was the unit of analysis. We computed statistical significance for differentiation (Fst) and linkage disequilibrium (nSL) statistics at the pathway level. In terms of Fst, we found 21 and 12 pathways significantly differentiated at a q -value 10 significant pathways (in terms of Fst), comprising genes involved in the transduction of a large number of signals, like phospholipase PCLB1, which is expressed in the brain, or ITPR3, which has an important role in taste transduction. In terms of nSL, significant pathways were mainly related to reproductive performance (ovarian steroidogenesis), a similarly important target trait during domestication and modern animal breeding. Different levels of recombination cannot explain these results, since we found no correlation between Fst and recombination rate. However, we did find an increased ratio of deleterious mutations in domestic vs. wild populations, suggesting a relaxed functional constraint associated with the domestication and breeding processes. Purifying selection was, nevertheless, stronger in significantly differentiated pathways than in random pathways, mainly in Europe. We conclude that pathway analysis facilitates the biological interpretation of genome-wide studies. Notably, in the case of pig, behavior played an important role, among other physiological

  3. A functional genomics approach using metabolomics and in silico pathway analysis

    DEFF Research Database (Denmark)

    Förster, Jochen; Gombert, Andreas Karoly; Nielsen, Jens

    2002-01-01

    analysis techniques and changes in the genotype will in many cases lead to different metabolite profiles. Here, a theoretical framework that may be applied to identify the function of orphan genes is presented. The approach is based on a combination of metabolome analysis combined with in silico pathway...

  4. Metabolic pathway analysis using a nash equilibrium approach

    NARCIS (Netherlands)

    Lucia, Angelo; DiMaggio, Peter A.; Alonso-Martinez, Diego

    2018-01-01

    A novel approach to metabolic network analysis using a Nash Equilibrium (NE) formulation is proposed in which enzymes are considered players in a multi-player game. Each player has its own payoff function with the objective of minimizing the Gibbs free energy associated with the biochemical

  5. Probabilistic methods in combinatorial analysis

    CERN Document Server

    Sachkov, Vladimir N

    2014-01-01

    This 1997 work explores the role of probabilistic methods for solving combinatorial problems. These methods not only provide the means of efficiently using such notions as characteristic and generating functions, the moment method and so on but also let us use the powerful technique of limit theorems. The basic objects under investigation are nonnegative matrices, partitions and mappings of finite sets, with special emphasis on permutations and graphs, and equivalence classes specified on sequences of finite length consisting of elements of partially ordered sets; these specify the probabilist

  6. Methods in quantitative image analysis.

    Science.gov (United States)

    Oberholzer, M; Ostreicher, M; Christen, H; Brühlmann, M

    1996-05-01

    The main steps of image analysis are image capturing, image storage (compression), correcting imaging defects (e.g. non-uniform illumination, electronic-noise, glare effect), image enhancement, segmentation of objects in the image and image measurements. Digitisation is made by a camera. The most modern types include a frame-grabber, converting the analog-to-digital signal into digital (numerical) information. The numerical information consists of the grey values describing the brightness of every point within the image, named a pixel. The information is stored in bits. Eight bits are summarised in one byte. Therefore, grey values can have a value between 0 and 256 (2(8)). The human eye seems to be quite content with a display of 5-bit images (corresponding to 64 different grey values). In a digitised image, the pixel grey values can vary within regions that are uniform in the original scene: the image is noisy. The noise is mainly manifested in the background of the image. For an optimal discrimination between different objects or features in an image, uniformity of illumination in the whole image is required. These defects can be minimised by shading correction [subtraction of a background (white) image from the original image, pixel per pixel, or division of the original image by the background image]. The brightness of an image represented by its grey values can be analysed for every single pixel or for a group of pixels. The most frequently used pixel-based image descriptors are optical density, integrated optical density, the histogram of the grey values, mean grey value and entropy. The distribution of the grey values existing within an image is one of the most important characteristics of the image. However, the histogram gives no information about the texture of the image. The simplest way to improve the contrast of an image is to expand the brightness scale by spreading the histogram out to the full available range. Rules for transforming the grey value

  7. Moyer's method of mixed dentition analysis: a meta-analysis ...

    African Journals Online (AJOL)

    The applicability of tables derived from the data Moyer used to other ethnic groups has ... This implies that Moyer's method of prediction may have population variations. ... Key Words: meta-analysis, mixed dentition analysis, Moyer's method

  8. Applying critical analysis - main methods

    Directory of Open Access Journals (Sweden)

    Miguel Araujo Alonso

    2012-02-01

    Full Text Available What is the usefulness of critical appraisal of literature? Critical analysis is a fundamental condition for the correct interpretation of any study that is subject to review. In epidemiology, in order to learn how to read a publication, we must be able to analyze it critically. Critical analysis allows us to check whether a study fulfills certain previously established methodological inclusion and exclusion criteria. This is frequently used in conducting systematic reviews although eligibility criteria are generally limited to the study design. Critical analysis of literature and be done implicitly while reading an article, as in reading for personal interest, or can be conducted in a structured manner, using explicit and previously established criteria. The latter is done when formally reviewing a topic.

  9. Screening key candidate genes and pathways involved in insulinoma by microarray analysis.

    Science.gov (United States)

    Zhou, Wuhua; Gong, Li; Li, Xuefeng; Wan, Yunyan; Wang, Xiangfei; Li, Huili; Jiang, Bin

    2018-06-01

    Insulinoma is a rare type tumor and its genetic features remain largely unknown. This study aimed to search for potential key genes and relevant enriched pathways of insulinoma.The gene expression data from GSE73338 were downloaded from Gene Expression Omnibus database. Differentially expressed genes (DEGs) were identified between insulinoma tissues and normal pancreas tissues, followed by pathway enrichment analysis, protein-protein interaction (PPI) network construction, and module analysis. The expressions of candidate key genes were validated by quantitative real-time polymerase chain reaction (RT-PCR) in insulinoma tissues.A total of 1632 DEGs were obtained, including 1117 upregulated genes and 514 downregulated genes. Pathway enrichment results showed that upregulated DEGs were significantly implicated in insulin secretion, and downregulated DEGs were mainly enriched in pancreatic secretion. PPI network analysis revealed 7 hub genes with degrees more than 10, including GCG (glucagon), GCGR (glucagon receptor), PLCB1 (phospholipase C, beta 1), CASR (calcium sensing receptor), F2R (coagulation factor II thrombin receptor), GRM1 (glutamate metabotropic receptor 1), and GRM5 (glutamate metabotropic receptor 5). DEGs involved in the significant modules were enriched in calcium signaling pathway, protein ubiquitination, and platelet degranulation. Quantitative RT-PCR data confirmed that the expression trends of these hub genes were similar to the results of bioinformatic analysis.The present study demonstrated that candidate DEGs and enriched pathways were the potential critical molecule events involved in the development of insulinoma, and these findings were useful for better understanding of insulinoma genesis.

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

    Directory of Open Access Journals (Sweden)

    Yingrong Chen

    2015-01-01

    Full Text Available 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.

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

    Directory of Open Access Journals (Sweden)

    Salcedo Mauricio

    2007-09-01

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

  12. Energy pathway analysis - a hydrogen fuel cycle framework for system studies

    International Nuclear Information System (INIS)

    Badin, J.S.; Tagore, S.

    1997-01-01

    An analytical framework has been developed that can be used to estimate a range of life-cycle costs and impacts that result from the incremental production, storage, transport, and use of different fuels or energy carriers, such as hydrogen, electricity, natural gas, and gasoline. This information is used in a comparative analysis of energy pathways. The pathways provide the U.S. Department of Energy (DOE) with an indication of near-, mid-, and long-term technologies that have the greatest potential for advancement and can meet the cost goals. The methodology and conceptual issues are discussed. Also presented are results for selected pathways from the E3 (Energy, Economics, Emissions) Pathway Analysis Model. This model will be expanded to consider networks of pathways and to be compatible with a linear programming optimization processor. Scenarios and sets of constraints (energy demands, sources, emissions) will be defined so the effects on energy transformation activities included in the solution and on the total optimized system cost can be investigated. This evaluation will be used as a guide to eliminate technically feasible pathways if they are not cost effective or do not meet the threshold requirements for the market acceptance. (Author)

  13. Analysis of culture media screening data by projection to latent pathways: The case of Pichia pastoris X-33.

    Science.gov (United States)

    Isidro, Inês A; Ferreira, Ana R; Clemente, João J; Cunha, António E; Oliveira, Rui

    2016-01-10

    Cell culture media formulations contain hundreds of individual components in water solutions which have complex interactions with metabolic pathways. The currently used statistical design methods are empirical and very limited to explore such a large design space. In a previous work we developed a computational method called projection to latent pathways (PLP), which was conceived to maximize covariance between envirome and fluxome data under the constraint of metabolic network elementary flux modes (EFM). More specifically, PLP identifies a minimal set of EFMs (i.e., pathways) with the highest possible correlation with envirome and fluxome measurements. In this paper we extend the concept for the analysis of culture media screening data to investigate how culture medium components up-regulate or down-regulate key metabolic pathways. A Pichia pastoris X-33 strain was cultivated in 26 shake flask experiments with variations in trace elements concentrations and basal medium dilution, based on the standard BSM+PTM1 medium. PLP identified 3 EFMs (growth, maintenance and by-product formation) describing 98.8% of the variance in observed fluxes. Furthermore, PLP presented an overall predictive power comparable to that of PLS regression. Our results show iron and manganese at concentrations close to the PTM1 standard inhibit overall metabolic activity, while the main salts concentration (BSM) affected mainly energy expenditures for cellular maintenance. Copyright © 2015 Elsevier B.V. All rights reserved.

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

    Science.gov (United States)

    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

  15. Trial Sequential Methods for Meta-Analysis

    Science.gov (United States)

    Kulinskaya, Elena; Wood, John

    2014-01-01

    Statistical methods for sequential meta-analysis have applications also for the design of new trials. Existing methods are based on group sequential methods developed for single trials and start with the calculation of a required information size. This works satisfactorily within the framework of fixed effects meta-analysis, but conceptual…

  16. Static analysis of a Model of the LDL degradation pathway

    DEFF Research Database (Denmark)

    Pilegaard, Henrik; Nielson, Flemming; Nielson, Hanne Riis

    2005-01-01

    BioAmbients is a derivative of mobile ambients that has shown promise of describing interesting features of the behaviour of biological systems. As for other ambient calculi static program analysis can be used to compute safe approximations of the behavior of modelled systems. We use these tools ...... to model and analyse the production of cholesterol in living cells and show that we are able to pinpoint the difference in behaviour between models of healthy systems and models of mutated systems giving rise to known diseases....

  17. Genomic analysis and selected molecular pathways in rare cancers

    International Nuclear Information System (INIS)

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

    2012-01-01

    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. (paper)

  18. A techno-economic analysis of EU renewable electricity policy pathways in 2030

    International Nuclear Information System (INIS)

    Río, Pablo del; Resch, Gustav; Ortner, Andre; Liebmann, Lukas; Busch, Sebastian; Panzer, Christian

    2017-01-01

    The aim of this paper is to assess several pathways of a harmonised European policy framework for supporting renewable electricity (RES-E) in a 2030 horizon according to different criteria. The pathways combine two main dimensions: degrees of harmonisation and instruments and design elements. A quantitative model-based analysis with the Green-X model is provided. The results of the simulations show that there are small differences between the evaluated cases regarding effectiveness. All the policy pathways score similarly with respect to RES-E deployment, i.e., with different degrees of harmonisation and whether using a feed-in tariff, a feed-in premium, a quota system with banding or a quota without banding scheme. In contrast, the policy costs clearly differ across the pathways, but the differences can mostly be attributed to the instruments rather than to the degrees of harmonisation. This is also the case with other criteria (static and dynamic efficiency and the socioeconomic and environmental benefits in terms of CO2 emissions and fossil fuels avoided). Both the degree of harmonisation and the choice of instrument influence the distribution of support costs across countries. Finally, our findings suggest that keeping strengthened national support leads to similar results to other policy pathways. - Highlights: • Pathways of a harmonised European policy framework for renewable electricity in 2030. • Two main dimensions: degrees of harmonisation and instruments. • A quantitative model-based analysis based on the Green-X model. • Small differences between the pathways regarding the effectiveness criterion. • Important differences between pathways regarding other assessment criteria.

  19. Effect of curcumin on aged Drosophila melanogaster: a pathway prediction analysis.

    Science.gov (United States)

    Zhang, Zhi-guo; Niu, Xu-yan; Lu, Ai-ping; Xiao, Gary Guishan

    2015-02-01

    To re-analyze the data published in order to explore plausible biological pathways that can be used to explain the anti-aging effect of curcumin. Microarray data generated from other study aiming to investigate effect of curcumin on extending lifespan of Drosophila melanogaster were further used for pathway prediction analysis. The differentially expressed genes were identified by using GeneSpring GX with a criterion of 3.0-fold change. Two Cytoscape plugins including BisoGenet and molecular complex detection (MCODE) were used to establish the protein-protein interaction (PPI) network based upon differential genes in order to detect highly connected regions. The function annotation clustering tool of Database for Annotation, Visualization and Integrated Discovery (DAVID) was used for pathway analysis. A total of 87 genes expressed differentially in D. melanogaster melanogaster treated with curcumin were identified, among which 50 were up-regulated significantly and 37 were remarkably down-regulated in D. melanogaster melanogaster treated with curcumin. Based upon these differential genes, PPI network was constructed with 1,082 nodes and 2,412 edges. Five highly connected regions in PPI networks were detected by MCODE algorithm, suggesting anti-aging effect of curcumin may be underlined through five different pathways including Notch signaling pathway, basal transcription factors, cell cycle regulation, ribosome, Wnt signaling pathway, and p53 pathway. Genes and their associated pathways in D. melanogaster melanogaster treated with anti-aging agent curcumin were identified using PPI network and MCODE algorithm, suggesting that curcumin may be developed as an alternative therapeutic medicine for treating aging-associated diseases.

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

    Directory of Open Access Journals (Sweden)

    Michael Volpers

    Full Text Available 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

  1. Info-Gap robustness pathway method for transitioning of urban drainage systems under deep uncertainties.

    Science.gov (United States)

    Zischg, Jonatan; Goncalves, Mariana L R; Bacchin, Taneha Kuzniecow; Leonhardt, Günther; Viklander, Maria; van Timmeren, Arjan; Rauch, Wolfgang; Sitzenfrei, Robert

    2017-09-01

    In the urban water cycle, there are different ways of handling stormwater runoff. Traditional systems mainly rely on underground piped, sometimes named 'gray' infrastructure. New and so-called 'green/blue' ambitions aim for treating and conveying the runoff at the surface. Such concepts are mainly based on ground infiltration and temporal storage. In this work a methodology to create and compare different planning alternatives for stormwater handling on their pathways to a desired system state is presented. Investigations are made to assess the system performance and robustness when facing the deeply uncertain spatial and temporal developments in the future urban fabric, including impacts caused by climate change, urbanization and other disruptive events, like shifts in the network layout and interactions of 'gray' and 'green/blue' structures. With the Info-Gap robustness pathway method, three planning alternatives are evaluated to identify critical performance levels at different stages over time. This novel methodology is applied to a real case study problem where a city relocation process takes place during the upcoming decades. In this case study it is shown that hybrid systems including green infrastructures are more robust with respect to future uncertainties, compared to traditional network design.

  2. N-of-1-pathways MixEnrich: advancing precision medicine via single-subject analysis in discovering dynamic changes of transcriptomes.

    Science.gov (United States)

    Li, Qike; Schissler, A Grant; Gardeux, Vincent; Achour, Ikbel; Kenost, Colleen; Berghout, Joanne; Li, Haiquan; Zhang, Hao Helen; Lussier, Yves A

    2017-05-24

    Transcriptome analytic tools are commonly used across patient cohorts to develop drugs and predict clinical outcomes. However, as precision medicine pursues more accurate and individualized treatment decisions, these methods are not designed to address single-patient transcriptome analyses. We previously developed and validated the N-of-1-pathways framework using two methods, Wilcoxon and Mahalanobis Distance (MD), for personal transcriptome analysis derived from a pair of samples of a single patient. Although, both methods uncover concordantly dysregulated pathways, they are not designed to detect dysregulated pathways with up- and down-regulated genes (bidirectional dysregulation) that are ubiquitous in biological systems. We developed N-of-1-pathways MixEnrich, a mixture model followed by a gene set enrichment test, to uncover bidirectional and concordantly dysregulated pathways one patient at a time. We assess its accuracy in a comprehensive simulation study and in a RNA-Seq data analysis of head and neck squamous cell carcinomas (HNSCCs). In presence of bidirectionally dysregulated genes in the pathway or in presence of high background noise, MixEnrich substantially outperforms previous single-subject transcriptome analysis methods, both in the simulation study and the HNSCCs data analysis (ROC Curves; higher true positive rates; lower false positive rates). Bidirectional and concordant dysregulated pathways uncovered by MixEnrich in each patient largely overlapped with the quasi-gold standard compared to other single-subject and cohort-based transcriptome analyses. The greater performance of MixEnrich presents an advantage over previous methods to meet the promise of providing accurate personal transcriptome analysis to support precision medicine at point of care.

  3. Hybrid methods for cybersecurity analysis :

    Energy Technology Data Exchange (ETDEWEB)

    Davis, Warren Leon,; Dunlavy, Daniel M.

    2014-01-01

    Early 2010 saw a signi cant change in adversarial techniques aimed at network intrusion: a shift from malware delivered via email attachments toward the use of hidden, embedded hyperlinks to initiate sequences of downloads and interactions with web sites and network servers containing malicious software. Enterprise security groups were well poised and experienced in defending the former attacks, but the new types of attacks were larger in number, more challenging to detect, dynamic in nature, and required the development of new technologies and analytic capabilities. The Hybrid LDRD project was aimed at delivering new capabilities in large-scale data modeling and analysis to enterprise security operators and analysts and understanding the challenges of detection and prevention of emerging cybersecurity threats. Leveraging previous LDRD research e orts and capabilities in large-scale relational data analysis, large-scale discrete data analysis and visualization, and streaming data analysis, new modeling and analysis capabilities were quickly brought to bear on the problems in email phishing and spear phishing attacks in the Sandia enterprise security operational groups at the onset of the Hybrid project. As part of this project, a software development and deployment framework was created within the security analyst work ow tool sets to facilitate the delivery and testing of new capabilities as they became available, and machine learning algorithms were developed to address the challenge of dynamic threats. Furthermore, researchers from the Hybrid project were embedded in the security analyst groups for almost a full year, engaged in daily operational activities and routines, creating an atmosphere of trust and collaboration between the researchers and security personnel. The Hybrid project has altered the way that research ideas can be incorporated into the production environments of Sandias enterprise security groups, reducing time to deployment from months and

  4. Global analysis of the sporulation pathway of Clostridium difficile.

    Science.gov (United States)

    Fimlaid, Kelly A; Bond, Jeffrey P; Schutz, Kristin C; Putnam, Emily E; Leung, Jacqueline M; Lawley, Trevor D; Shen, Aimee

    2013-01-01

    The Gram-positive, spore-forming pathogen Clostridium difficile is the leading definable cause of healthcare-associated diarrhea worldwide. C. difficile infections are difficult to treat because of their frequent recurrence, which can cause life-threatening complications such as pseudomembranous colitis. The spores of C. difficile are responsible for these high rates of recurrence, since they are the major transmissive form of the organism and resistant to antibiotics and many disinfectants. Despite the importance of spores to the pathogenesis of C. difficile, little is known about their composition or formation. Based on studies in Bacillus subtilis and other Clostridium spp., the sigma factors σ(F), σ(E), σ(G), and σ(K) are predicted to control the transcription of genes required for sporulation, although their specific functions vary depending on the organism. In order to determine the roles of σ(F), σ(E), σ(G), and σ(K) in regulating C. difficile sporulation, we generated loss-of-function mutations in genes encoding these sporulation sigma factors and performed RNA-Sequencing to identify specific sigma factor-dependent genes. This analysis identified 224 genes whose expression was collectively activated by sporulation sigma factors: 183 were σ(F)-dependent, 169 were σ(E)-dependent, 34 were σ(G)-dependent, and 31 were σ(K)-dependent. In contrast with B. subtilis, C. difficile σ(E) was dispensable for σ(G) activation, σ(G) was dispensable for σ(K) activation, and σ(F) was required for post-translationally activating σ(G). Collectively, these results provide the first genome-wide transcriptional analysis of genes induced by specific sporulation sigma factors in the Clostridia and highlight that diverse mechanisms regulate sporulation sigma factor activity in the Firmicutes.

  5. Anticipating future innovation pathways through large data analysis

    CERN Document Server

    Chiavetta, Denise; Porter, Alan; Saritas, Ozcan

    2016-01-01

    This book aims to identify promising future developmental opportunities and applications for Tech Mining. Specifically, the enclosed contributions will pursue three converging themes: The increasing availability of electronic text data resources relating to Science, Technology & Innovation (ST&I) The multiple methods that are able to treat this data effectively and incorporate means to tap into human expertise and interests Translating those analyses to provide useful intelligence on likely future developments of particular emerging S&T targets. Tech Mining can be defined as text analyses of ST&I information resources to generate Competitive Technical Intelligence (CTI). It combines bibliometrics and advanced text analytic, drawing on specialized knowledge pertaining to ST&I. Tech Mining may also be viewed as a special form of “Big Data” analytics because it searches on a target emerging technology (or key organization) of interest in global databases. One then downloads, typically, th...

  6. Microparticle analysis system and method

    Science.gov (United States)

    Morrison, Dennis R. (Inventor)

    2007-01-01

    A device for analyzing microparticles is provided which includes a chamber with an inlet and an outlet for respectively introducing and dispensing a flowing fluid comprising microparticles, a light source for providing light through the chamber and a photometer for measuring the intensity of light transmitted through individual microparticles. The device further includes an imaging system for acquiring images of the fluid. In some cases, the device may be configured to identify and determine a quantity of the microparticles within the fluid. Consequently, a method for identifying and tracking microparticles in motion is contemplated herein. The method involves flowing a fluid comprising microparticles in laminar motion through a chamber, transmitting light through the fluid, measuring the intensities of the light transmitted through the microparticles, imaging the fluid a plurality of times and comparing at least some of the intensities of light between different images of the fluid.

  7. An evaluation of the implementation of maternal obesity pathways of care: a mixed methods study with data integration.

    Directory of Open Access Journals (Sweden)

    Nicola Heslehurst

    Full Text Available Maternal obesity has multiple associated risks and requires substantial intervention. This research evaluated the implementation of maternal obesity care pathways from multiple stakeholder perspectives.A simultaneous mixed methods model with data integration was used. Three component studies were given equal priority. 1: Semi-structured qualitative interviews explored obese pregnant women's experiences of being on the pathways. 2: A quantitative and qualitative postal survey explored healthcare professionals' experiences of delivering the pathways. 3: A case note audit quantitatively assessed pathway compliance. Data were integrated using following a thread and convergence coding matrix methods to search for agreement and disagreement between studies.Study 1: Four themes were identified: women's overall (positive and negative views of the pathways; knowledge and understanding of the pathways; views on clinical and weight management advice and support; and views on the information leaflet. Key results included positive views of receiving additional clinical care, negative experiences of risk communication, and weight management support was considered a priority. Study 2: Healthcare professionals felt the pathways were worthwhile, facilitated good practice, and increased confidence. Training was consistently identified as being required. Healthcare professionals predominantly focussed on women's response to sensitive obesity communication. Study 3: There was good compliance with antenatal clinical interventions. However, there was poor compliance with public health and postnatal interventions. There were some strong areas of agreement between component studies which can inform future development of the pathways. However, disagreement between studies included a lack of shared priorities between healthcare professionals and women, different perspectives on communication issues, and different perspectives on women's prioritisation of weight

  8. An Evaluation of the Implementation of Maternal Obesity Pathways of Care: A Mixed Methods Study with Data Integration

    Science.gov (United States)

    Heslehurst, Nicola; Dinsdale, Sarah; Sedgewick, Gillian; Simpson, Helen; Sen, Seema; Summerbell, Carolyn Dawn; Rankin, Judith

    2015-01-01

    Objectives Maternal obesity has multiple associated risks and requires substantial intervention. This research evaluated the implementation of maternal obesity care pathways from multiple stakeholder perspectives. Study Design A simultaneous mixed methods model with data integration was used. Three component studies were given equal priority. 1: Semi-structured qualitative interviews explored obese pregnant women’s experiences of being on the pathways. 2: A quantitative and qualitative postal survey explored healthcare professionals’ experiences of delivering the pathways. 3: A case note audit quantitatively assessed pathway compliance. Data were integrated using following a thread and convergence coding matrix methods to search for agreement and disagreement between studies. Results Study 1: Four themes were identified: women’s overall (positive and negative) views of the pathways; knowledge and understanding of the pathways; views on clinical and weight management advice and support; and views on the information leaflet. Key results included positive views of receiving additional clinical care, negative experiences of risk communication, and weight management support was considered a priority. Study 2: Healthcare professionals felt the pathways were worthwhile, facilitated good practice, and increased confidence. Training was consistently identified as being required. Healthcare professionals predominantly focussed on women’s response to sensitive obesity communication. Study 3: There was good compliance with antenatal clinical interventions. However, there was poor compliance with public health and postnatal interventions. There were some strong areas of agreement between component studies which can inform future development of the pathways. However, disagreement between studies included a lack of shared priorities between healthcare professionals and women, different perspectives on communication issues, and different perspectives on women

  9. Environmental-pathways analysis for evaluation of a low-level waste disposal site

    International Nuclear Information System (INIS)

    Lee, D.W.; Ketelle, R.H.; Pin, F.G.; Hill, G.S.

    1983-01-01

    The suitability of a site for the shallow land burial of low-level waste is evaluated by an environmental-pathways analysis. The environmental-pathways analysis considers the probable paths for the transport of contamination to man and models the long-term transport of contamination to determine the resulting dose-to-man. The model of the long-term transport of contamination is developed for a proposed site using data obtained from a comprehensive laboratory and field investigation. The proposed site is located at the US Department of Energy Portsmouth Reservation, Piketon, Ohio and is planned to accept low-level radioactive waste generated by the enrichment of uranium. Laboratory studies were performed to characterize the waste and determine the wastes' leaching and retardation characteristics with site soils and groundwater. Comprehensive drilling, sampling and laboratory investigations were performed to provide the necessary information for interpreting the site's geology and hydrology. Field tests were performed to further quantify the site's hydrology. The pathway of greatest concern is the migration of contaminated groundwater and subsequent consumption by man. This pathway was modeled using a numerical simulation of the long-term transport of contamination. Conservative scenarios were developed for leachate generation and migration through the geohydrologic system. The dose-to-man determined from the pathways analysis formed the basis for evaluating site acceptability and providing recommendations for site design and development

  10. Life Cycle Greenhouse Gas Analysis of Multiple Vehicle Fuel Pathways in China

    Directory of Open Access Journals (Sweden)

    Tianduo Peng

    2017-11-01

    Full Text Available The Tsinghua University Life Cycle Analysis Model (TLCAM is applied to calculate the life cycle fossil energy consumption and greenhouse gas (GHG emissions for more than 20 vehicle fuel pathways in China. In addition to conventional gasoline and diesel, these include coal- and gas-based vehicle fuels, and electric vehicle (EV pathways. The results indicate the following. (1 China’s current dependence on coal and relative low-efficiency processes limits the potential for most alternative fuel pathways to decrease energy consumption and emissions; (2 Future low-carbon electricity pathways offer more obvious advantages, with coal-based pathways needing to adopt carbon dioxide capture and storage technology to compete; (3 A well-to-wheels analysis of the fossil energy consumption of vehicles fueled by compressed natural gas and liquefied natural gas (LNG showed that they are comparable to conventional gasoline vehicles. However, importing rather than domestically producing LNG for vehicle use can decrease domestic GHG emissions by 35% and 31% compared with those of conventional gasoline and diesel vehicles, respectively; (4 The manufacturing and recovery of battery and vehicle in the EV analysis has significant impact on the overall ability of EVs to decrease fossil energy consumption and GHG emissions from ICEVs.

  11. Environmental pathways analysis for evaluation of a low-level waste disposal site

    International Nuclear Information System (INIS)

    Lee, D.W.; Ketelle, R.H.; Pin, F.G.; Hill, G.S.

    1984-01-01

    The suitability of a site for the shallow land burial of low-level waste is evaluated by an environmental pathways analysis. The environmental pathways analysis considers the probable paths for the transport of contamination to man and models the long-term transport of contamination to determine the resulting dose to man. The model of the long-term transport of contamination is developed for a proposed site using data obtained from a comprehensive laboratory and field investigation. The proposed site is located at the US Department of Energy Portsmouth Reservation, Piketon, Ohio, and is planned to accept low-level radioactive waste generated by the enrichment of uranium. Laboratory studies were performed to characterize the waste and determine the wastes' leaching and retardation characteristics with site soils and groundwater. Comprehensive drilling, sampling and laboratory investigations were performed to provide the necessary information for interpreting the site's geology and hydrology. Field tests were performed to further quantify the site's hydrology. The pathway of greatest concern is the migration of contaminated groundwater and subsequent consumption by man. This pathway was modelled using a numerical simulation of the long-term transport of contamination. Conservative scenarios were developed for leachate generation and migration through the geohydrologic system. The dose to man determined from the pathways analysis formed the basis for evaluating site acceptability and providing recommendations for site design and development. (author)

  12. Large-scale transcriptome analysis reveals arabidopsis metabolic pathways are frequently influenced by different pathogens.

    Science.gov (United States)

    Jiang, Zhenhong; He, Fei; Zhang, Ziding

    2017-07-01

    Through large-scale transcriptional data analyses, we highlighted the importance of plant metabolism in plant immunity and identified 26 metabolic pathways that were frequently influenced by the infection of 14 different pathogens. Reprogramming of plant metabolism is a common phenomenon in plant defense responses. Currently, a large number of transcriptional profiles of infected tissues in Arabidopsis (Arabidopsis thaliana) have been deposited in public databases, which provides a great opportunity to understand the expression patterns of metabolic pathways during plant defense responses at the systems level. Here, we performed a large-scale transcriptome analysis based on 135 previously published expression samples, including 14 different pathogens, to explore the expression pattern of Arabidopsis metabolic pathways. Overall, metabolic genes are significantly changed in expression during plant defense responses. Upregulated metabolic genes are enriched on defense responses, and downregulated genes are enriched on photosynthesis, fatty acid and lipid metabolic processes. Gene set enrichment analysis (GSEA) identifies 26 frequently differentially expressed metabolic pathways (FreDE_Paths) that are differentially expressed in more than 60% of infected samples. These pathways are involved in the generation of energy, fatty acid and lipid metabolism as well as secondary metabolite biosynthesis. Clustering analysis based on the expression levels of these 26 metabolic pathways clearly distinguishes infected and control samples, further suggesting the importance of these metabolic pathways in plant defense responses. By comparing with FreDE_Paths from abiotic stresses, we find that the expression patterns of 26 FreDE_Paths from biotic stresses are more consistent across different infected samples. By investigating the expression correlation between transcriptional factors (TFs) and FreDE_Paths, we identify several notable relationships. Collectively, the current study

  13. Integrated bioinformatics analysis reveals key candidate genes and pathways in breast cancer.

    Science.gov (United States)

    Wang, Yuzhi; Zhang, Yi; Huang, Qian; Li, Chengwen

    2018-04-19

    Breast cancer (BC) is the leading malignancy in women worldwide, yet relatively little is known about the genes and signaling pathways involved in BC tumorigenesis and progression. The present study aimed to elucidate potential key candidate genes and pathways in BC. Five gene expression profile data sets (GSE22035, GSE3744, GSE5764, GSE21422 and GSE26910) were downloaded from the Gene Expression Omnibus (GEO) database, which included data from 113 tumorous and 38 adjacent non‑tumorous tissue samples. Differentially expressed genes (DEGs) were identified using t‑tests in the limma R package. These DEGs were subsequently investigated by pathway enrichment analysis and a protein‑protein interaction (PPI) network was constructed. The most significant module from the PPI network was selected for pathway enrichment analysis. In total, 227 DEGs were identified, of which 82 were upregulated and 145 were downregulated. Pathway enrichment analysis results revealed that the upregulated DEGs were mainly enriched in 'cell division', the 'proteinaceous extracellular matrix (ECM)', 'ECM structural constituents' and 'ECM‑receptor interaction', whereas downregulated genes were mainly enriched in 'response to drugs', 'extracellular space', 'transcriptional activator activity' and the 'peroxisome proliferator‑activated receptor signaling pathway'. The PPI network contained 174 nodes and 1,257 edges. DNA topoisomerase 2‑a, baculoviral inhibitor of apoptosis repeat‑containing protein 5, cyclin‑dependent kinase 1, G2/mitotic‑specific cyclin‑B1 and kinetochore protein NDC80 homolog were identified as the top 5 hub genes. Furthermore, the genes in the most significant module were predominantly involved in 'mitotic nuclear division', 'mid‑body', 'protein binding' and 'cell cycle'. In conclusion, the DEGs, relative pathways and hub genes identified in the present study may aid in understanding of the molecular mechanisms underlying BC progression and provide

  14. Using logic model methods in systematic review synthesis: describing complex pathways in referral management interventions.

    Science.gov (United States)

    Baxter, Susan K; Blank, Lindsay; Woods, Helen Buckley; Payne, Nick; Rimmer, Melanie; Goyder, Elizabeth

    2014-05-10

    There is increasing interest in innovative methods to carry out systematic reviews of complex interventions. Theory-based approaches, such as logic models, have been suggested as a means of providing additional insights beyond that obtained via conventional review methods. This paper reports the use of an innovative method which combines systematic review processes with logic model techniques to synthesise a broad range of literature. The potential value of the model produced was explored with stakeholders. The review identified 295 papers that met the inclusion criteria. The papers consisted of 141 intervention studies and 154 non-intervention quantitative and qualitative articles. A logic model was systematically built from these studies. The model outlines interventions, short term outcomes, moderating and mediating factors and long term demand management outcomes and impacts. Interventions were grouped into typologies of practitioner education, process change, system change, and patient intervention. Short-term outcomes identified that may result from these interventions were changed physician or patient knowledge, beliefs or attitudes and also interventions related to changed doctor-patient interaction. A range of factors which may influence whether these outcomes lead to long term change were detailed. Demand management outcomes and intended impacts included content of referral, rate of referral, and doctor or patient satisfaction. The logic model details evidence and assumptions underpinning the complex pathway from interventions to demand management impact. The method offers a useful addition to systematic review methodologies. PROSPERO registration number: CRD42013004037.

  15. Infinitesimal methods of mathematical analysis

    CERN Document Server

    Pinto, J S

    2004-01-01

    This modern introduction to infinitesimal methods is a translation of the book Métodos Infinitesimais de Análise Matemática by José Sousa Pinto of the University of Aveiro, Portugal and is aimed at final year or graduate level students with a background in calculus. Surveying modern reformulations of the infinitesimal concept with a thoroughly comprehensive exposition of important and influential hyperreal numbers, the book includes previously unpublished material on the development of hyperfinite theory of Schwartz distributions and its application to generalised Fourier transforms and harmon

  16. Development of advanced MCR task analysis methods

    International Nuclear Information System (INIS)

    Na, J. C.; Park, J. H.; Lee, S. K.; Kim, J. K.; Kim, E. S.; Cho, S. B.; Kang, J. S.

    2008-07-01

    This report describes task analysis methodology for advanced HSI designs. Task analyses was performed by using procedure-based hierarchical task analysis and task decomposition methods. The results from the task analysis were recorded in a database. Using the TA results, we developed static prototype of advanced HSI and human factors engineering verification and validation methods for an evaluation of the prototype. In addition to the procedure-based task analysis methods, workload estimation based on the analysis of task performance time and analyses for the design of information structure and interaction structures will be necessary

  17. Current status of methods for shielding analysis

    International Nuclear Information System (INIS)

    Engle, W.W.

    1980-01-01

    Current methods used in shielding analysis and recent improvements in those methods are discussed. The status of methods development is discussed based on needs cited at the 1977 International Conference on Reactor Shielding. Additional areas where methods development is needed are discussed

  18. A systematic model identification method for chemical transformation pathways – the case of heroin biomarkers in wastewater

    DEFF Research Database (Denmark)

    Ramin, Pedram; Valverde Pérez, Borja; Polesel, Fabio

    2017-01-01

    This study presents a novel statistical approach for identifying sequenced chemical transformation pathways in combination with reaction kinetics models. The proposed method relies on sound uncertainty propagation by considering parameter ranges and associated probability distribution obtained...... at any given transformation pathway levels as priors for parameter estimation at any subsequent transformation levels. The method was applied to calibrate a model predicting the transformation in untreated wastewater of six biomarkers, excreted following human metabolism of heroin and codeine. The method....... Results obtained suggest that the method developed has the potential to outperform conventional approaches in terms of prediction accuracy, transformation pathway identification and parameter identifiability. This method can be used in conjunction with optimal experimental designs to effectively identify...

  19. Parallel imaging of Drosophila embryos for quantitative analysis of genetic perturbations of the Ras pathway

    Directory of Open Access Journals (Sweden)

    Yogesh Goyal

    2017-07-01

    Full Text Available The Ras pathway patterns the poles of the Drosophila embryo by downregulating the levels and activity of a DNA-binding transcriptional repressor Capicua (Cic. We demonstrate that the spatiotemporal pattern of Cic during this signaling event can be harnessed for functional studies of mutations in the Ras pathway in human diseases. Our approach relies on a new microfluidic device that enables parallel imaging of Cic dynamics in dozens of live embryos. We found that although the pattern of Cic in early embryos is complex, it can be accurately approximated by a product of one spatial profile and one time-dependent amplitude. Analysis of these functions of space and time alone reveals the differential effects of mutations within the Ras pathway. Given the highly conserved nature of Ras-dependent control of Cic, our approach provides new opportunities for functional analysis of multiple sequence variants from developmental abnormalities and cancers.

  20. A gene pathway analysis highlights the role of cellular adhesion molecules in multiple sclerosis susceptibility

    DEFF Research Database (Denmark)

    Damotte, V; Guillot-Noel, L; Patsopoulos, N A

    2014-01-01

    adhesion molecule (CAMs) biological pathway using Cytoscape software. This network is a strong candidate, as it is involved in the crossing of the blood-brain barrier by the T cells, an early event in MS pathophysiology, and is used as an efficient therapeutic target. We drew up a list of 76 genes...... in interaction with other genes as a group. Pathway analysis is an alternative way to highlight such group of genes. Using SNP association P-values from eight multiple sclerosis (MS) GWAS data sets, we performed a candidate pathway analysis for MS susceptibility by considering genes interacting in the cell...... belonging to the CAM network. We highlighted 64 networks enriched with CAM genes with low P-values. Filtering by a percentage of CAM genes up to 50% and rejecting enriched signals mainly driven by transcription factors, we highlighted five networks associated with MS susceptibility. One of them, constituted...

  1. Sensitivity analysis of intracellular signaling pathway kinetics predicts targets for stem cell fate control.

    Directory of Open Access Journals (Sweden)

    Alborz Mahdavi

    2007-07-01

    Full Text Available 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.

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

    Energy Technology Data Exchange (ETDEWEB)

    Hermsen, Sanne A.B., E-mail: Sanne.Hermsen@rivm.nl [Centre for Health Protection, National Institute for Public Health and the Environment (RIVM), P.O. Box 1, 3720 BA Bilthoven (Netherlands); Department of Toxicogenomics, Maastricht University, P.O. Box 616, 6200 MD, Maastricht (Netherlands); Institute for Risk Assessment Sciences (IRAS), Utrecht University, P.O. Box 80.178, 3508 TD, Utrecht (Netherlands); Pronk, Tessa E. [Centre for Health Protection, National Institute for Public Health and the Environment (RIVM), P.O. Box 1, 3720 BA Bilthoven (Netherlands); Department of Toxicogenomics, Maastricht University, P.O. Box 616, 6200 MD, Maastricht (Netherlands); Brandhof, Evert-Jan van den [Centre for Environmental Quality, National Institute for Public Health and the Environment (RIVM), P.O. Box 1, 3720 BA Bilthoven (Netherlands); Ven, Leo T.M. van der [Centre for Health Protection, National Institute for Public Health and the Environment (RIVM), P.O. Box 1, 3720 BA Bilthoven (Netherlands); Piersma, Aldert H. [Centre for Health Protection, National Institute for Public Health and the Environment (RIVM), P.O. Box 1, 3720 BA Bilthoven (Netherlands); Institute for Risk Assessment Sciences (IRAS), Utrecht University, P.O. Box 80.178, 3508 TD, Utrecht (Netherlands)

    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.

  3. In Silico Analysis of Putrefaction Pathways in Bacteria and Its Implication in Colorectal Cancer

    Directory of Open Access Journals (Sweden)

    Harrisham Kaur

    2017-11-01

    Full Text Available Fermentation of undigested proteins in human gastrointestinal tract (gut by the resident microbiota, a process called bacterial putrefaction, can sometimes disrupt the gut homeostasis. In this process, essential amino acids (e.g., histidine, tryptophan, etc. that are required by the host may be utilized by the gut microbes. In addition, some of the products of putrefaction, like ammonia, putrescine, cresol, indole, phenol, etc., have been implicated in the disease pathogenesis of colorectal cancer (CRC. We have investigated bacterial putrefaction pathways that are known to be associated with such metabolites. Results of the comprehensive in silico analysis of the selected putrefaction pathways across bacterial genomes revealed presence of these pathways in limited bacterial groups. Majority of these bacteria are commonly found in human gut. These include Bacillus, Clostridium, Enterobacter, Escherichia, Fusobacterium, Salmonella, etc. Interestingly, while pathogens utilize almost all the analyzed pathways, commensals prefer putrescine and H2S production pathways for metabolizing the undigested proteins. Further, comparison of the putrefaction pathways in the gut microbiomes of healthy, carcinoma and adenoma datasets indicate higher abundances of putrefying bacteria in the carcinoma stage of CRC. The insights obtained from the present study indicate utilization of possible microbiome-based therapies to minimize the adverse effects of gut microbiome in enteric diseases.

  4. Epistasis Analysis for Estrogen Metabolic and Signaling Pathway Genes on Young Ischemic Stroke Patients

    Science.gov (United States)

    Hsieh, Yi-Chen; Jeng, Jiann-Shing; Lin, Huey-Juan; Hu, Chaur-Jong; Yu, Chia-Chen; Lien, Li-Ming; Peng, Giia-Sheun; Chen, Chin-I; Tang, Sung-Chun; Chi, Nai-Fang; Tseng, Hung-Pin; Chern, Chang-Ming; Hsieh, Fang-I; Bai, Chyi-Huey; Chen, Yi-Rhu; Chiou, Hung-Yi; Jeng, Jiann-Shing; Tang, Sung-Chun; Yeh, Shin-Joe; Tsai, Li-Kai; Kong, Shin; Lien, Li-Ming; Chiu, Hou-Chang; Chen, Wei-Hung; Bai, Chyi-Huey; Huang, Tzu-Hsuan; Chi-Ieong, Lau; Wu, Ya-Ying; Yuan, Rey-Yue; Hu, Chaur-Jong; Sheu, Jau- Jiuan; Yu, Jia-Ming; Ho, Chun-Sum; Chen, Chin-I; Sung, Jia-Ying; Weng, Hsing-Yu; Han, Yu-Hsuan; Huang, Chun-Ping; Chung, Wen-Ting; Ke, Der-Shin; Lin, Huey-Juan; Chang, Chia-Yu; Yeh, Poh-Shiow; Lin, Kao-Chang; Cheng, Tain-Junn; Chou, Chih-Ho; Yang, Chun-Ming; Peng, Giia-Sheun; Lin, Jiann-Chyun; Hsu, Yaw-Don; Denq, Jong-Chyou; Lee, Jiunn-Tay; Hsu, Chang-Hung; Lin, Chun-Chieh; Yen, Che-Hung; Cheng, Chun-An; Sung, Yueh-Feng; Chen, Yuan-Liang; Lien, Ming-Tung; Chou, Chung-Hsing; Liu, Chia-Chen; Yang, Fu-Chi; Wu, Yi-Chung; Tso, An-Chen; Lai, Yu- Hua; Chiang, Chun-I; Tsai, Chia-Kuang; Liu, Meng-Ta; Lin, Ying-Che; Hsu, Yu-Chuan; Chen, Chih-Hung; Sung, Pi-Shan; Chern, Chang-Ming; Hu, Han-Hwa; Wong, Wen-Jang; Luk, Yun-On; Hsu, Li-Chi; Chung, Chih-Ping; Tseng, Hung-Pin; Liu, Chin-Hsiung; Lin, Chun-Liang; Lin, Hung-Chih; Hu, Chaur-Jong

    2012-01-01

    Background Endogenous estrogens play an important role in the overall cardiocirculatory system. However, there are no studies exploring the hormone metabolism and signaling pathway genes together on ischemic stroke, including sulfotransferase family 1E (SULT1E1), catechol-O-methyl-transferase (COMT), and estrogen receptor α (ESR1). Methods A case-control study was conducted on 305 young ischemic stroke subjects aged ≦ 50 years and 309 age-matched healthy controls. SULT1E1 -64G/A, COMT Val158Met, ESR1 c.454−397 T/C and c.454−351 A/G genes were genotyped and compared between cases and controls to identify single nucleotide polymorphisms associated with ischemic stroke susceptibility. Gene-gene interaction effects were analyzed using entropy-based multifactor dimensionality reduction (MDR), classification and regression tree (CART), and traditional multiple regression models. Results COMT Val158Met polymorphism showed a significant association with susceptibility of young ischemic stroke among females. There was a two-way interaction between SULT1E1 -64G/A and COMT Val158Met in both MDR and CART analysis. The logistic regression model also showed there was a significant interaction effect between SULT1E1 -64G/A and COMT Val158Met on ischemic stroke of the young (P for interaction = 0.0171). We further found that lower estradiol level could increase the risk of young ischemic stroke for those who carry either SULT1E1 or COMT risk genotypes, showing a significant interaction effect (P for interaction = 0.0174). Conclusions Our findings support that a significant epistasis effect exists among estrogen metabolic and signaling pathway genes and gene-environment interactions on young ischemic stroke subjects. PMID:23112845

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

    Energy Technology Data Exchange (ETDEWEB)

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

    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

  6. A critical assessment of theoretical methods for finding reaction pathways and transition states of surface processes

    International Nuclear Information System (INIS)

    Klimes, JirI; Michaelides, Angelos; Bowler, David R

    2010-01-01

    The performance of a variety of techniques for locating transition states on potential energy surfaces is evaluated within the density functional theory framework. Diffusion of a water molecule across NaCl(001) and HCl bond breaking on the same surface are treated as general test cases; the former is an example of a low barrier diffusion process and the latter an example of a relatively high barrier covalent bond rupture event. The methods considered include the nudged elastic band (NEB), Dewar, Healy and Stewart (DHS), dimer, constrained optimization (CO), activation-relaxation technique (ART) and one-side growing string (OGS) as well as novel combinations of the DHS with growing string (DHS + GS) and DHS plus climbing image (CI-DHS). A key conclusion to come from this study is that the NEB method is relatively fast, especially when just a single (climbing) image is used. Indeed, using more images represents an unnecessary computational burden for our set of processes. The dimer method exhibits variable performance; being poor for the water diffusion processes, which have small activation energies, but much more efficient for the HCl bond breaking process which has a higher barrier. When only a poor initial guess of the transition state geometry is available, the CI-DHS scheme is one of the most efficient techniques considered. And as a means to quickly establish an approximate minimum energy pathway the DHS + GS scheme offers some potential.

  7. Combined geophysical methods for mapping infiltration pathways at the Aurora Water Aquifer recharge and recovery site

    Science.gov (United States)

    Jasper, Cameron A.

    Although aquifer recharge and recovery systems are a sustainable, decentralized, low cost, and low energy approach for the reclamation, treatment, and storage of post- treatment wastewater, they can suffer from poor infiltration rates and the development of a near-surface clogging layer within infiltration ponds. One such aquifer recharge and recovery system, the Aurora Water site in Colorado, U.S.A, functions at about 25% of its predicted capacity to recharge floodplain deposits by flooding infiltration ponds with post-treatment wastewater extracted from river bank aquifers along the South Platte River. The underwater self-potential method was developed to survey self-potential signals at the ground surface in a flooded infiltration pond for mapping infiltration pathways. A method for using heat as a groundwater tracer within the infiltration pond used an array of in situ high-resolution temperature sensing probes. Both relatively positive and negative underwater self-potential anomalies are consistent with observed recovery well pumping rates and specific discharge estimates from temperature data. Results from electrical resistivity tomography and electromagnetics surveys provide consistent electrical conductivity distributions associated with sediment textures. A lab method was developed for resistivity tests of near-surface sediment samples. Forward numerical modeling synthesizes the geophysical information to best match observed self- potential anomalies and provide permeability distributions, which is important for effective aquifer recharge and recovery system design, and optimization strategy development.

  8. Metabolic-flux analysis of hydrogen production pathway in Citrobacter amalonaticus Y19

    Energy Technology Data Exchange (ETDEWEB)

    Oh, You-Kwan; Kim, Mi-Sun [Bioenergy Research Center, Korea Institute of Energy Research, Daejeon 305-343 (Korea); Kim, Heung-Joo; Park, Sunghoon [Department of Chemical and Biochemical Engineering and Institute for Environmental Technology and Industry, Pusan National University, Busan 609-735 (Korea); Ryu, Dewey D.Y. [Biochemical Engineering Program, Department of Chemical Engineering and Material Science, University of California, Davis, CA 95616 (United States)

    2008-03-15

    For the newly isolated chemoheterotrophic bacterium Citrobacter amalonaticus Y19, anaerobic glucose metabolism and hydrogen (H{sub 2}) production pathway were studied using batch cultivation and an in silico metabolic-flux analysis. Batch cultivation was conducted under varying initial glucose concentration between 1.5 and 9.5 g/L with quantitative measurement of major metabolites to obtain accurate carbon material balance. The metabolic flux of Y19 was analyzed using a metabolic-pathway model which was constructed from 81 biochemical reactions. The linear optimization program MetaFluxNet was employed for the analysis. When the specific growth rate of cells was chosen as an objective function, the model described the batch culture characteristics of Ci. amalonaticus Y19 reasonably well. When the specific H{sub 2} production rate was selected as an objective function, on the other hand, the achievable maximal H{sub 2} production yield (8.7molH{sub 2}/mol glucose) and the metabolic pathway enabling the high H{sub 2} yield were identified. The pathway involved non-native NAD(P)-linked hydrogenase and H{sub 2} production from NAD(P)H which were supplied at a high rate from glucose degradation through the pentose phosphate pathway. (author)

  9. Microarray analysis reveals genetic pathways modulated by tipifarnib in acute myeloid leukemia

    International Nuclear Information System (INIS)

    Raponi, Mitch; Belly, Robert T; Karp, Judith E; Lancet, Jeffrey E; Atkins, David; Wang, Yixin

    2004-01-01

    Farnesyl protein transferase inhibitors (FTIs) were originally developed to inhibit oncogenic ras, however it is now clear that there are several other potential targets for this drug class. The FTI tipifarnib (ZARNESTRA™, R115777) has recently demonstrated clinical responses in adults with refractory and relapsed acute leukemias. This study was conducted to identify genetic markers and pathways that are regulated by tipifarnib in acute myeloid leukemia (AML). Tipifarnib-mediated gene expression changes in 3 AML cell lines and bone marrow samples from two patients with AML were analyzed on a cDNA microarray containing approximately 7000 human genes. Pathways associated with these expression changes were identified using the Ingenuity Pathway Analysis tool. The expression analysis identified a common set of genes that were regulated by tipifarnib in three leukemic cell lines and in leukemic blast cells isolated from two patients who had been treated with tipifarnib. Association of modulated genes with biological functional groups identified several pathways affected by tipifarnib including cell signaling, cytoskeletal organization, immunity, and apoptosis. Gene expression changes were verified in a subset of genes using real time RT-PCR. Additionally, regulation of apoptotic genes was found to correlate with increased Annexin V staining in the THP-1 cell line but not in the HL-60 cell line. The genetic networks derived from these studies illuminate some of the biological pathways affected by FTI treatment while providing a proof of principle for identifying candidate genes that might be used as surrogate biomarkers of drug activity

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

    Science.gov (United States)

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

    2011-10-04

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

  11. Gene expression meta-analysis identifies metastatic pathways and transcription factors in breast cancer

    DEFF Research Database (Denmark)

    Thomassen, Mads; Tan, Qihua; Kruse, Torben

    2008-01-01

    ABSTRACT: BACKGROUND: Metastasis is believed to progress in several steps including different pathways but the determination and understanding of these mechanisms is still fragmentary. Microarray analysis of gene expression patterns in breast tumors has been used to predict outcome in recent stud...

  12. Earth analysis methods, subsurface feature detection methods, earth analysis devices, and articles of manufacture

    Science.gov (United States)

    West, Phillip B [Idaho Falls, ID; Novascone, Stephen R [Idaho Falls, ID; Wright, Jerry P [Idaho Falls, ID

    2011-09-27

    Earth analysis methods, subsurface feature detection methods, earth analysis devices, and articles of manufacture are described. According to one embodiment, an earth analysis method includes engaging a device with the earth, analyzing the earth in a single substantially lineal direction using the device during the engaging, and providing information regarding a subsurface feature of the earth using the analysis.

  13. Parametric Methods for Order Tracking Analysis

    DEFF Research Database (Denmark)

    Nielsen, Jesper Kjær; Jensen, Tobias Lindstrøm

    2017-01-01

    Order tracking analysis is often used to find the critical speeds at which structural resonances are excited by a rotating machine. Typically, order tracking analysis is performed via non-parametric methods. In this report, however, we demonstrate some of the advantages of using a parametric method...

  14. Combining qualitative and quantitative operational research methods to inform quality improvement in pathways that span multiple settings

    Science.gov (United States)

    Crowe, Sonya; Brown, Katherine; Tregay, Jenifer; Wray, Jo; Knowles, Rachel; Ridout, Deborah A; Bull, Catherine; Utley, Martin

    2017-01-01

    Background Improving integration and continuity of care across sectors within resource constraints is a priority in many health systems. Qualitative operational research methods of problem structuring have been used to address quality improvement in services involving multiple sectors but not in combination with quantitative operational research methods that enable targeting of interventions according to patient risk. We aimed to combine these methods to augment and inform an improvement initiative concerning infants with congenital heart disease (CHD) whose complex care pathway spans multiple sectors. Methods Soft systems methodology was used to consider systematically changes to services from the perspectives of community, primary, secondary and tertiary care professionals and a patient group, incorporating relevant evidence. Classification and regression tree (CART) analysis of national audit datasets was conducted along with data visualisation designed to inform service improvement within the context of limited resources. Results A ‘Rich Picture’ was developed capturing the main features of services for infants with CHD pertinent to service improvement. This was used, along with a graphical summary of the CART analysis, to guide discussions about targeting interventions at specific patient risk groups. Agreement was reached across representatives of relevant health professions and patients on a coherent set of targeted recommendations for quality improvement. These fed into national decisions about service provision and commissioning. Conclusions When tackling complex problems in service provision across multiple settings, it is important to acknowledge and work with multiple perspectives systematically and to consider targeting service improvements in response to confined resources. Our research demonstrates that applying a combination of qualitative and quantitative operational research methods is one approach to doing so that warrants further

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

    Science.gov (United States)

    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. © The Author 2016. Published by Oxford University Press on behalf of the Society for Experimental Biology. All rights

  16. The delayed neutron method of uranium analysis

    International Nuclear Information System (INIS)

    Wall, T.

    1989-01-01

    The technique of delayed neutron analysis (DNA) is discussed. The DNA rig installed on the MOATA reactor, the assay standards and the types of samples which have been assayed are described. Of the total sample throughput of about 55,000 units since the uranium analysis service began, some 78% has been concerned with analysis of uranium ore samples derived from mining and exploration. Delayed neutron analysis provides a high sensitivity, low cost uranium analysis method for both uranium exploration and other applications. It is particularly suitable for analysis of large batch samples and for non-destructive analysis over a wide range of matrices. 8 refs., 4 figs., 3 tabs

  17. Understanding sharps injuries in home healthcare: The Safe Home Care qualitative methods study to identify pathways for injury prevention.

    Science.gov (United States)

    Markkanen, Pia; Galligan, Catherine; Laramie, Angela; Fisher, June; Sama, Susan; Quinn, Margaret

    2015-04-11

    Home healthcare is one of the fastest growing sectors in the United States. Percutaneous injuries from sharp medical devices (sharps) are a source of bloodborne pathogen infections among home healthcare workers and community members. Sharps use and disposal practices in the home are highly variable and there is no comprehensive analysis of the system of sharps procurement, use and disposal in home healthcare. This gap is a barrier to effective public health interventions. The objectives of this study were to i) identify the full range of pathways by which sharps enter and exit the home, stakeholders involved, and barriers for using sharps with injury prevention features; and ii) assess the leverage points for preventive interventions. This study employed qualitative research methods to develop two systems maps of the use of sharps and prevention of sharps injuries in home healthcare. Twenty-six in-depth interview sessions were conducted including home healthcare agency clinicians, public health practitioners, sharps device manufacturers, injury prevention advocates, pharmacists and others. Interview transcripts were audio-recorded and analyzed thematically using NVIVO qualitative research analysis software. Analysis of supporting archival material also was conducted. All findings guided development of the two maps. Sharps enter the home via multiple complex pathways involving home healthcare providers and home users. The providers reported using sharps with injury prevention features. However, home users' sharps seldom had injury prevention features and sharps were commonly re-used for convenience and cost-savings. Improperly discarded sharps present hazards to caregivers, waste handlers, and community members. The most effective intervention potential exists at the beginning of the sharps systems maps where interventions can eliminate or minimize sharps injuries, in particular with needleless treatment methods and sharps with injury prevention features

  18. Radiochemistry and nuclear methods of analysis

    International Nuclear Information System (INIS)

    Ehmann, W.D.; Vance, D.

    1991-01-01

    This book provides both the fundamentals of radiochemistry as well as specific applications of nuclear techniques to analytical chemistry. It includes such areas of application as radioimmunoassay and activation techniques using very short-lined indicator radionuclides. It emphasizes the current nuclear methods of analysis such as neutron activation PIXE, nuclear reaction analysis, Rutherford backscattering, isotope dilution analysis and others

  19. Computational methods in power system analysis

    CERN Document Server

    Idema, Reijer

    2014-01-01

    This book treats state-of-the-art computational methods for power flow studies and contingency analysis. In the first part the authors present the relevant computational methods and mathematical concepts. In the second part, power flow and contingency analysis are treated. Furthermore, traditional methods to solve such problems are compared to modern solvers, developed using the knowledge of the first part of the book. Finally, these solvers are analyzed both theoretically and experimentally, clearly showing the benefits of the modern approach.

  20. Constructing an Intelligent Patent Network Analysis Method

    Directory of Open Access Journals (Sweden)

    Chao-Chan Wu

    2012-11-01

    Full Text Available Patent network analysis, an advanced method of patent analysis, is a useful tool for technology management. This method visually displays all the relationships among the patents and enables the analysts to intuitively comprehend the overview of a set of patents in the field of the technology being studied. Although patent network analysis possesses relative advantages different from traditional methods of patent analysis, it is subject to several crucial limitations. To overcome the drawbacks of the current method, this study proposes a novel patent analysis method, called the intelligent patent network analysis method, to make a visual network with great precision. Based on artificial intelligence techniques, the proposed method provides an automated procedure for searching patent documents, extracting patent keywords, and determining the weight of each patent keyword in order to generate a sophisticated visualization of the patent network. This study proposes a detailed procedure for generating an intelligent patent network that is helpful for improving the efficiency and quality of patent analysis. Furthermore, patents in the field of Carbon Nanotube Backlight Unit (CNT-BLU were analyzed to verify the utility of the proposed method.

  1. Microarray analysis of peripheral blood lymphocytes from ALS patients and the SAFE detection of the KEGG ALS pathway

    Science.gov (United States)

    2011-01-01

    Background Sporadic amyotrophic lateral sclerosis (sALS) is a motor neuron disease with poorly understood etiology. Results of gene expression profiling studies of whole blood from ALS patients have not been validated and are difficult to relate to ALS pathogenesis because gene expression profiles depend on the relative abundance of the different cell types present in whole blood. We conducted microarray analyses using Agilent Human Whole Genome 4 × 44k Arrays on a more homogeneous cell population, namely purified peripheral blood lymphocytes (PBLs), from ALS patients and healthy controls to identify molecular signatures possibly relevant to ALS pathogenesis. Methods Differentially expressed genes were determined by LIMMA (Linear Models for MicroArray) and SAM (Significance Analysis of Microarrays) analyses. The SAFE (Significance Analysis of Function and Expression) procedure was used to identify molecular pathway perturbations. Proteasome inhibition assays were conducted on cultured peripheral blood mononuclear cells (PBMCs) from ALS patients to confirm alteration of the Ubiquitin/Proteasome System (UPS). Results For the first time, using SAFE in a global gene ontology analysis (gene set size 5-100), we show significant perturbation of the KEGG (Kyoto Encyclopedia of Genes and Genomes) ALS pathway of motor neuron degeneration in PBLs from ALS patients. This was the only KEGG disease pathway significantly upregulated among 25, and contributing genes, including SOD1, represented 54% of the encoded proteins or protein complexes of the KEGG ALS pathway. Further SAFE analysis, including gene set sizes >100, showed that only neurodegenerative diseases (4 out of 34 disease pathways) including ALS were significantly upregulated. Changes in UBR2 expression correlated inversely with time since onset of disease and directly with ALSFRS-R, implying that UBR2 was increased early in the course of ALS. Cultured PBMCs from ALS patients accumulated more ubiquitinated proteins

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

    Energy Technology Data Exchange (ETDEWEB)

    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. Text analysis methods, text analysis apparatuses, and articles of manufacture

    Science.gov (United States)

    Whitney, Paul D; Willse, Alan R; Lopresti, Charles A; White, Amanda M

    2014-10-28

    Text analysis methods, text analysis apparatuses, and articles of manufacture are described according to some aspects. In one aspect, a text analysis method includes accessing information indicative of data content of a collection of text comprising a plurality of different topics, using a computing device, analyzing the information indicative of the data content, and using results of the analysis, identifying a presence of a new topic in the collection of text.

  4. Evaluating the effect of clinical care pathways on quality of cancer care: analysis of breast, colon and rectal cancer pathways.

    Science.gov (United States)

    Bao, Han; Yang, Fengjuan; Su, Shaofei; Wang, Xinyu; Zhang, Meiqi; Xiao, Yaming; Jiang, Hao; Wang, Jiaying; Liu, Meina

    2016-05-01

    Substantial gaps exist between clinical practice and evidence-based cancer care, potentially leading to adverse clinical outcomes and decreased quality of life for cancer patients. This study aimed to evaluate the usefulness of clinical pathways as a tool for improving quality of cancer care, using breast, colon, and rectal cancer pathways as demonstrations. Newly diagnosed patients with invasive breast, colon, and rectal cancer were enrolled as pre-pathway groups, while patients with the same diagnoses treated according to clinical pathways were recruited for post-pathway groups. Compliance with preoperative core biopsy or fine-needle aspiration, utilization of sentinel lymph node biopsy, and proportion of patients whose tumor hormone receptor status was stated in pathology report were significantly increased after implementation of clinical pathway for breast cancer. For colon cancer, compliance with two care processes was significantly improved: surgical resection with anastomosis and resection of at least 12 lymph nodes. Regarding rectal cancer, there was a significant increase in compliance with preoperative evaluation of depth of tumor invasion, total mesorectal excision treatment of middle- or low-position rectal cancer, and proportion of patients who had undergone rectal cancer surgery whose pathology report included margin status. Moreover, total length of hospital stay was decreased remarkably for all three cancer types, and postoperative complications remained unchanged following implementation of the clinical pathways. Clinical pathways can improve compliance with standard care by implementing evidence-based quality indicators in daily practice, which could serve as a useful tool for narrowing the gap between clinical practice and evidence-based care.

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

    Directory of Open Access Journals (Sweden)

    Chen Xu

    2016-09-01

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

  6. Combining qualitative and quantitative operational research methods to inform quality improvement in pathways that span multiple settings.

    Science.gov (United States)

    Crowe, Sonya; Brown, Katherine; Tregay, Jenifer; Wray, Jo; Knowles, Rachel; Ridout, Deborah A; Bull, Catherine; Utley, Martin

    2017-08-01

    Improving integration and continuity of care across sectors within resource constraints is a priority in many health systems. Qualitative operational research methods of problem structuring have been used to address quality improvement in services involving multiple sectors but not in combination with quantitative operational research methods that enable targeting of interventions according to patient risk. We aimed to combine these methods to augment and inform an improvement initiative concerning infants with congenital heart disease (CHD) whose complex care pathway spans multiple sectors. Soft systems methodology was used to consider systematically changes to services from the perspectives of community, primary, secondary and tertiary care professionals and a patient group, incorporating relevant evidence. Classification and regression tree (CART) analysis of national audit datasets was conducted along with data visualisation designed to inform service improvement within the context of limited resources. A 'Rich Picture' was developed capturing the main features of services for infants with CHD pertinent to service improvement. This was used, along with a graphical summary of the CART analysis, to guide discussions about targeting interventions at specific patient risk groups. Agreement was reached across representatives of relevant health professions and patients on a coherent set of targeted recommendations for quality improvement. These fed into national decisions about service provision and commissioning. When tackling complex problems in service provision across multiple settings, it is important to acknowledge and work with multiple perspectives systematically and to consider targeting service improvements in response to confined resources. Our research demonstrates that applying a combination of qualitative and quantitative operational research methods is one approach to doing so that warrants further consideration. Published by the BMJ Publishing Group

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

    Directory of Open Access Journals (Sweden)

    Paolo Cossu-Rocca

    Full Text Available 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.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.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.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.

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

    Science.gov (United States)

    Cossu-Rocca, Paolo; Orrù, Sandra; 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

    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. 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. 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. 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.

  9. Nuclear analysis methods. Rudiments of radiation protection

    International Nuclear Information System (INIS)

    Roth, E.

    1998-01-01

    The nuclear analysis methods are generally used to analyse radioactive elements but they can be used also for chemical analysis, with fields such analysis and characterization of traces. The principles of radiation protection are explained (ALARA), the biological effects of ionizing radiations are given, elements and units used in radiation protection are reminded in tables. A part of this article is devoted to how to use radiation protection in a nuclear analysis laboratory. (N.C.)

  10. Diagnosis of accessory conduction pathway using ECG-gated emission CT analysis

    International Nuclear Information System (INIS)

    Misaki, Takuro; Mukai, Keiichi; Tsubota, Makoto; Iwa, Takashi; Nakajima, Ken-ichi; Hisada, Kin-ichi

    1987-01-01

    Pinpointing the location of accessory conduction pathway (ACP) is of great importance in the surgical treatment for Wolff-Parkinson-White (WPW) syndrome. For this purpose, this study explored the usefulness of ECG-gated emission computed tomography (Gated-ECT) in 30 patients who preoperatively underwent Gated-ECT. The site of earliest contraction at level of atrioventicular valves, obtained on tomographic phase analysis, was compared with the site of earliest activation, obtained on epicardial mapping during surgery. The concordance rate of the two methods was 94 % (28/30). Among them, one patient was found to have the association of corrected transposition of great arteries on Gated-ECT. Gated-ECT was, however, of limited value in differentiating right posterior ACP from right postseptal ACP. The discordance between the sites of earliest contraction and activation, which was observed in the two others, was likely due to decreased wall motion resulting from myocardial disturbance. Gated-ECT may have a diagnostic potential for the location of ACP, especially in view of providing images that corresponded to the surgical anatomy. (Namekawa, K.)

  11. Integrated analysis of DNA methylation and gene expression reveals specific signaling pathways associated with platinum resistance in ovarian cancer

    Directory of Open Access Journals (Sweden)

    Chung Jae

    2009-06-01

    Full Text Available Abstract Background Cisplatin and carboplatin are the primary first-line therapies for the treatment of ovarian cancer. However, resistance to these platinum-based drugs occurs in the large majority of initially responsive tumors, resulting in fully chemoresistant, fatal disease. Although the precise mechanism(s underlying the development of platinum resistance in late-stage ovarian cancer patients currently remains unknown, CpG-island (CGI methylation, a phenomenon strongly associated with aberrant gene silencing and ovarian tumorigenesis, may contribute to this devastating condition. Methods To model the onset of drug resistance, and investigate DNA methylation and gene expression alterations associated with platinum resistance, we treated clonally derived, drug-sensitive A2780 epithelial ovarian cancer cells with increasing concentrations of cisplatin. After several cycles of drug selection, the isogenic drug-sensitive and -resistant pairs were subjected to global CGI methylation and mRNA expression microarray analyses. To identify chemoresistance-associated, biological pathways likely impacted by DNA methylation, promoter CGI methylation and mRNA expression profiles were integrated and subjected to pathway enrichment analysis. Results Promoter CGI methylation revealed a positive association (Spearman correlation of 0.99 between the total number of hypermethylated CGIs and GI50 values (i.e., increased drug resistance following successive cisplatin treatment cycles. In accord with that result, chemoresistance was reversible by DNA methylation inhibitors. Pathway enrichment analysis revealed hypermethylation-mediated repression of cell adhesion and tight junction pathways and hypomethylation-mediated activation of the cell growth-promoting pathways PI3K/Akt, TGF-beta, and cell cycle progression, which may contribute to the onset of chemoresistance in ovarian cancer cells. Conclusion Selective epigenetic disruption of distinct biological

  12. Proliferation Resistance: Acquisition/Diversion Pathway Analysis for the DUPIC Fuel Cycle

    International Nuclear Information System (INIS)

    Ko, Won Il; Chang, Hong Lae; Song, Dae Yong; Lee, Ho Hee; Kwon, Eun Ha; Jeong, Chang Joon; Kim, Ho Dong

    2009-07-01

    Within the International Project on Innovative Nuclear Reactors and Fuel Cycles (INPRO), a methodology for evaluating proliferation resistance (INPRO PR methodology) has been developed. However, it remains to develop the methodology to evaluate User Requirements (UR) 4 regarding multiplicity and robustness of barriers against proliferation - innovative nuclear energy systems should incorporate multiple proliferation resistance features and measures. Since this requires an acquisition/diversion pathway analysis, this report describes a systematic approach developed for the identification and analysis of pathways for the acquisition of weapons-usable nuclear material using the DUPIC fuel cycle system. At the first step, the objectives of the proliferation were identified, including the quality and quantity of the material, the time required to acquire the material for the proliferation, thr capability of the potential proliferant country, etc. At the second step, the possible strategies, which the potential proliferant country could adopt, were identified: undeclared removal of nuclear material from the fuel cycle facilities; and further treatment of the diverted nuclear materials needed to acquire weapons-usable materials. At the final step, a systematic approach to select the plausible pathways for the acquisition/diversion of nuclear material during the whole fuel cycle has been developed. The coarse material diversion pathways for the DUPIC fuel cycle and the approach developed was reviewed and discussed at the experts meeting at the IAEA for its appropriateness and comprehensiveness

  13. Pathway Detection from Protein Interaction Networks and Gene Expression Data Using Color-Coding Methods and A* Search Algorithms

    Directory of Open Access Journals (Sweden)

    Cheng-Yu Yeh

    2012-01-01

    Full Text Available With the large availability of protein interaction networks and microarray data supported, to identify the linear paths that have biological significance in search of a potential pathway is a challenge issue. We proposed a color-coding method based on the characteristics of biological network topology and applied heuristic search to speed up color-coding method. In the experiments, we tested our methods by applying to two datasets: yeast and human prostate cancer networks and gene expression data set. The comparisons of our method with other existing methods on known yeast MAPK pathways in terms of precision and recall show that we can find maximum number of the proteins and perform comparably well. On the other hand, our method is more efficient than previous ones and detects the paths of length 10 within 40 seconds using CPU Intel 1.73GHz and 1GB main memory running under windows operating system.

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

    Science.gov (United States)

    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.

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

    Directory of Open Access Journals (Sweden)

    Eva Chovancova

    Full Text Available 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.

  16. CAVER 3.0: A Tool for the Analysis of Transport Pathways in Dynamic Protein Structures

    Science.gov (United States)

    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

  17. Shedding Light on the Mechanisms Underlying Health Disparities Through Community Participatory Methods: The Stress Pathway

    Science.gov (United States)

    Schetter, Christine Dunkel; Schafer, Peter; Lanzi, Robin Gaines; Clark-Kauffman, Elizabeth; Raju, Tonse N. K.; Hillemeier, Marianne M.

    2015-01-01

    Health disparities are large and persistent gaps in the rates of disease and death between racial/ethnic and socioeconomic status subgroups in the population. Stress is a major pathway hypothesized to explain such disparities. The Eunice Kennedy Shriver National Institute of Child Health and Human Development formed a community/research collaborative—the Community Child Health Network—to investigate disparities in maternal and child health in five high-risk communities. Using community participation methods, we enrolled a large cohort of African American/Black, Latino/Hispanic, and non-Hispanic/White mothers and fathers of newborns at the time of birth and followed them over 2 years. A majority had household incomes near or below the federal poverty level. Home interviews yielded detailed information regarding multiple types of stress such as major life events and many forms of chronic stress including racism. Several forms of stress varied markedly by racial/ethnic group and income, with decreasing stress as income increased among Caucasians but not among African Americans; other forms of stress varied by race/ethnicity or poverty alone. We conclude that greater sophistication in studying the many forms of stress and community partnership is necessary to uncover the mechanisms underlying health disparities in poor and ethnic-minority families and to implement community health interventions. PMID:26173227

  18. Shedding Light on the Mechanisms Underlying Health Disparities Through Community Participatory Methods: The Stress Pathway.

    Science.gov (United States)

    Dunkel Schetter, Christine; Schafer, Peter; Lanzi, Robin Gaines; Clark-Kauffman, Elizabeth; Raju, Tonse N K; Hillemeier, Marianne M

    2013-11-01

    Health disparities are large and persistent gaps in the rates of disease and death between racial/ethnic and socioeconomic status subgroups in the population. Stress is a major pathway hypothesized to explain such disparities. The Eunice Kennedy Shriver National Institute of Child Health and Human Development formed a community/research collaborative-the Community Child Health Network-to investigate disparities in maternal and child health in five high-risk communities. Using community participation methods, we enrolled a large cohort of African American/Black, Latino/Hispanic, and non-Hispanic/White mothers and fathers of newborns at the time of birth and followed them over 2 years. A majority had household incomes near or below the federal poverty level. Home interviews yielded detailed information regarding multiple types of stress such as major life events and many forms of chronic stress including racism. Several forms of stress varied markedly by racial/ethnic group and income, with decreasing stress as income increased among Caucasians but not among African Americans; other forms of stress varied by race/ethnicity or poverty alone. We conclude that greater sophistication in studying the many forms of stress and community partnership is necessary to uncover the mechanisms underlying health disparities in poor and ethnic-minority families and to implement community health interventions. © The Author(s) 2013.

  19. Comparison of methods for the analysis of relatively simple mediation models

    NARCIS (Netherlands)

    Rijnhart, Judith J.M.; Twisk, Jos W.R.; Chinapaw, Mai J.M.; de Boer, Michiel R.; Heymans, Martijn W.

    2017-01-01

    Background/aims Statistical mediation analysis is an often used method in trials, to unravel the pathways underlying the effect of an intervention on a particular outcome variable. Throughout the years, several methods have been proposed, such as ordinary least square (OLS) regression, structural

  20. Microlocal methods in the analysis of the boundary element method

    DEFF Research Database (Denmark)

    Pedersen, Michael

    1993-01-01

    The application of the boundary element method in numerical analysis is based upon the use of boundary integral operators stemming from multiple layer potentials. The regularity properties of these operators are vital in the development of boundary integral equations and error estimates. We show...

  1. Statistical methods for categorical data analysis

    CERN Document Server

    Powers, Daniel

    2008-01-01

    This book provides a comprehensive introduction to methods and models for categorical data analysis and their applications in social science research. Companion website also available, at https://webspace.utexas.edu/dpowers/www/

  2. Development of Ultraviolet Spectrophotometric Method for Analysis ...

    African Journals Online (AJOL)

    HP

    Method for Analysis of Lornoxicam in Solid Dosage. Forms. Sunit Kumar Sahoo ... testing. Mean recovery was 100.82 % for tablets. Low values of % RSD indicate .... Saharty E, Refaat YS, Khateeb ME. Stability-. Indicating. Spectrophotometric.

  3. An introduction to numerical methods and analysis

    CERN Document Server

    Epperson, James F

    2013-01-01

    Praise for the First Edition "". . . outstandingly appealing with regard to its style, contents, considerations of requirements of practice, choice of examples, and exercises.""-Zentralblatt MATH "". . . carefully structured with many detailed worked examples.""-The Mathematical Gazette The Second Edition of the highly regarded An Introduction to Numerical Methods and Analysis provides a fully revised guide to numerical approximation. The book continues to be accessible and expertly guides readers through the many available techniques of numerical methods and analysis. An Introduction to

  4. Hypothesis analysis methods, hypothesis analysis devices, and articles of manufacture

    Science.gov (United States)

    Sanfilippo, Antonio P [Richland, WA; Cowell, Andrew J [Kennewick, WA; Gregory, Michelle L [Richland, WA; Baddeley, Robert L [Richland, WA; Paulson, Patrick R [Pasco, WA; Tratz, Stephen C [Richland, WA; Hohimer, Ryan E [West Richland, WA

    2012-03-20

    Hypothesis analysis methods, hypothesis analysis devices, and articles of manufacture are described according to some aspects. In one aspect, a hypothesis analysis method includes providing a hypothesis, providing an indicator which at least one of supports and refutes the hypothesis, using the indicator, associating evidence with the hypothesis, weighting the association of the evidence with the hypothesis, and using the weighting, providing information regarding the accuracy of the hypothesis.

  5. A Gene Module-Based eQTL Analysis Prioritizing Disease Genes and Pathways in Kidney Cancer

    Directory of Open Access Journals (Sweden)

    Mary Qu Yang

    Full Text Available Clear cell renal cell carcinoma (ccRCC is the most common and most aggressive form of renal cell cancer (RCC. The incidence of RCC has increased steadily in recent years. The pathogenesis of renal cell cancer remains poorly understood. Many of the tumor suppressor genes, oncogenes, and dysregulated pathways in ccRCC need to be revealed for improvement of the overall clinical outlook of the disease. Here, we developed a systems biology approach to prioritize the somatic mutated genes that lead to dysregulation of pathways in ccRCC. The method integrated multi-layer information to infer causative mutations and disease genes. First, we identified differential gene modules in ccRCC by coupling transcriptome and protein-protein interactions. Each of these modules consisted of interacting genes that were involved in similar biological processes and their combined expression alterations were significantly associated with disease type. Then, subsequent gene module-based eQTL analysis revealed somatic mutated genes that had driven the expression alterations of differential gene modules. Our study yielded a list of candidate disease genes, including several known ccRCC causative genes such as BAP1 and PBRM1, as well as novel genes such as NOD2, RRM1, CSRNP1, SLC4A2, TTLL1 and CNTN1. The differential gene modules and their driver genes revealed by our study provided a new perspective for understanding the molecular mechanisms underlying the disease. Moreover, we validated the results in independent ccRCC patient datasets. Our study provided a new method for prioritizing disease genes and pathways. Keywords: ccRCC, Causative mutation, Pathways, Protein-protein interaction, Gene module, eQTL

  6. Identification of Personalized Chemoresistance Genes in Subtypes of Basal-Like Breast Cancer Based on Functional Differences Using Pathway Analysis.

    Directory of Open Access Journals (Sweden)

    Tong Wu

    Full Text Available Breast cancer is a highly heterogeneous disease that is clinically classified into several subtypes. Among these subtypes, basal-like breast cancer largely overlaps with triple-negative breast cancer (TNBC, and these two groups are generally studied together as a single entity. Differences in the molecular makeup of breast cancers can result in different treatment strategies and prognoses for patients with different breast cancer subtypes. Compared with other subtypes, basal-like and other ER+ breast cancer subtypes exhibit marked differences in etiologic factors, clinical characteristics and therapeutic potential. Anthracycline drugs are typically used as the first-line clinical treatment for basal-like breast cancer subtypes. However, certain patients develop drug resistance following chemotherapy, which can lead to disease relapse and death. Even among patients with basal-like breast cancer, there can be significant molecular differences, and it is difficult to identify specific drug resistance proteins in any given patient using conventional variance testing methods. Therefore, we designed a new method for identifying drug resistance genes. Subgroups, personalized biomarkers, and therapy targets were identified using cluster analysis of differentially expressed genes. We found that basal-like breast cancer could be further divided into at least four distinct subgroups, including two groups at risk for drug resistance and two groups characterized by sensitivity to pharmacotherapy. Based on functional differences among these subgroups, we identified nine biomarkers related to drug resistance: SYK, LCK, GAB2, PAWR, PPARG, MDFI, ZAP70, CIITA and ACTA1. Finally, based on the deviation scores of the examined pathways, 16 pathways were shown to exhibit varying degrees of abnormality in the various subgroups, indicating that patients with different subtypes of basal-like breast cancer can be characterized by differences in the functional status of

  7. Radionuclide migration pathways analysis for the Oak Ridge Central Waste Disposal Facility on the West Chestnut Ridge site

    International Nuclear Information System (INIS)

    Pin, F.G.; Witherspoon, J.P.; Lee, D.W.; Cannon, J.B.; Ketelle, R.H.

    1984-10-01

    A dose-to-man pathways analysis is performed for disposal of low-level radioactive waste at the Central Waste Disposal Facility on the West Chestnut Ridge Site. Both shallow land burial (trench) and aboveground (tumulus) disposal methods are considered. The waste volumes, characteristics, and radionuclide concentrations are those of waste streams anticipated from the Oak Ridge National Laboratory, the Y-12 Plant, and the Oak Ridge Gaseous Diffusion Plant. The site capacity for the waste streams is determined on the basis of the pathways analysis. The exposure pathways examined include (1) migration and transport of leachate from the waste disposal units to the Clinch River (via the groundwater medium for trench disposal and Ish Creek for tumulus disposal) and (2) those potentially associated with inadvertent intrusion following a 100-year period of institutional control: an individual resides on the site, inhales suspended particles of contaminated dust, ingests vegetables grown on the plot, consumes contaminated water from either an on-site well or from a nearby surface stream, and receives direct exposure from the contaminated soil. It is found that either disposal method would provide effective containment and isolation for the anticipated waste inventory. However, the proposed trench disposal method would provide more effective containment than tumuli because of sorption of some radionuclides in the soil. Persons outside the site boundary would receive radiation doses well below regulatory limits if they were to ingest water from the Clinch River. An inadvertent intruder could receive doses that approach regulatory limits; however, the likelihood of such intrusions and subsequent exposures is remote. 33 references, 31 figures, 28 tables

  8. Relating Actor Analysis Methods to Policy Problems

    NARCIS (Netherlands)

    Van der Lei, T.E.

    2009-01-01

    For a policy analyst the policy problem is the starting point for the policy analysis process. During this process the policy analyst structures the policy problem and makes a choice for an appropriate set of methods or techniques to analyze the problem (Goeller 1984). The methods of the policy

  9. Data mining and pathway analysis of glucose-6-phosphate dehydrogenase with natural language processing

    Science.gov (United States)

    Chen, Long; Zhang, Chunhua; Wang, Yanling; Li, Yuqian; Han, Qiaoqiao; Yang, Huixin; Zhu, Yuechun

    2017-01-01

    Human glucose-6-phosphate dehydrogenase (G6PD) is a crucial enzyme in the pentose phosphate pathway, and serves an important role in biosynthesis and the redox balance. G6PD deficiency is a major cause of neonatal jaundice and acute hemolyticanemia, and recently, G6PD has been associated with diseases including inflammation and cancer. The aim of the present study was to conduct a search of the National Center for Biotechnology Information PubMed library for articles discussing G6PD. Genes that were identified to be associated with G6PD were recorded, and the frequency at which each gene appeared was calculated. Gene ontology (GO), pathway and network analyses were then performed. A total of 98 G6PD-associated genes and 33 microRNAs (miRNAs) that potentially regulate G6PD were identified. The 98 G6PD-associated genes were then sub-classified into three functional groups by GO analysis, followed by analysis of function, pathway, network, and disease association. Out of the 47 signaling pathways identified, seven were significantly correlated with G6PD-associated genes. At least two out of four independent programs identified the 33 miRNAs that were predicted to target G6PD. miR-1207-5P, miR-1 and miR-125a-5p were predicted by all four software programs to target G6PD. The results of the present study revealed that dysregulation of G6PD was associated with cancer, autoimmune diseases, and oxidative stress-induced disorders. These results revealed the potential roles of G6PD-regulated signaling and metabolic pathways in the etiology of these diseases. PMID:28627690

  10. Nodal method for fast reactor analysis

    International Nuclear Information System (INIS)

    Shober, R.A.

    1979-01-01

    In this paper, a nodal method applicable to fast reactor diffusion theory analysis has been developed. This method has been shown to be accurate and efficient in comparison to highly optimized finite difference techniques. The use of an analytic solution to the diffusion equation as a means of determining accurate coupling relationships between nodes has been shown to be highly accurate and efficient in specific two-group applications, as well as in the current multigroup method

  11. Inelastic analysis methods for piping systems

    International Nuclear Information System (INIS)

    Boyle, J.T.; Spence, J.

    1980-01-01

    The analysis of pipework systems which operate in an environment where local inelastic strains are evident is one of the most demanding problems facing the stress analyst in the nuclear field. The spatial complexity of even the most modest system makes a detailed analysis using finite element techniques beyond the scope of current computer technology. For this reason the emphasis has been on simplified methods. It is the aim of this paper to provide a reasonably complete, state-of-the-art review of inelastic pipework analysis methods and to attempt to highlight areas where reliable information is lacking and further work is needed. (orig.)

  12. Enhancement of Nucleoside Production in Hirsutella sinensis Based on Biosynthetic Pathway Analysis

    Science.gov (United States)

    Liu, Zhi-Qiang; Zhang, Bo; Lin, Shan; Baker, Peter James; Chen, Mao-Sheng; Xue, Ya-Ping; Wu, Hui; Xu, Feng; Yuan, Shui-Jin; Teng, Yi; Wu, Ling-Fang

    2017-01-01

    To enhance nucleoside production in Hirsutella sinensis, the biosynthetic pathways of purine and pyrimidine nucleosides were constructed and verified. The differential expression analysis showed that purine nucleoside phosphorylase, inosine monophosphate dehydrogenase, and guanosine monophosphate synthase genes involved in purine nucleotide biosynthesis were significantly upregulated 16.56-fold, 8-fold, and 5.43-fold, respectively. Moreover, dihydroorotate dehydrogenase, uridine nucleosidase, uridine/cytidine monophosphate kinase, and inosine triphosphate pyrophosphatase genes participating in pyrimidine nucleoside biosynthesis were upregulated 4.53-fold, 10.63-fold, 4.26-fold, and 5.98-fold, respectively. To enhance the nucleoside production, precursors for synthesis of nucleosides were added based on the analysis of biosynthetic pathways. Uridine and cytidine contents, respectively, reached 5.04 mg/g and 3.54 mg/g when adding 2 mg/mL of ribose, resulting in an increase of 28.6% and 296% compared with the control, respectively. Meanwhile, uridine and cytidine contents, respectively, reached 10.83 mg/g 2.12 mg/g when adding 0.3 mg/mL of uracil, leading to an increase of 176.3% and 137.1%, respectively. This report indicated that fermentation regulation was an effective way to enhance the nucleoside production in H. sinensis based on biosynthetic pathway analysis. PMID:29333435

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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.

  15. GeneAnalytics Pathway Analysis and Genetic Overlap among Autism Spectrum Disorder, Bipolar Disorder and Schizophrenia

    Directory of Open Access Journals (Sweden)

    Naveen S. Khanzada

    2017-02-01

    Full Text Available Bipolar disorder (BPD and schizophrenia (SCH show similar neuropsychiatric behavioral disturbances, including impaired social interaction and communication, seen in autism spectrum disorder (ASD with multiple overlapping genetic and environmental influences implicated in risk and course of illness. GeneAnalytics software was used for pathway analysis and genetic profiling to characterize common susceptibility genes obtained from published lists for ASD (792 genes, BPD (290 genes and SCH (560 genes. Rank scores were derived from the number and nature of overlapping genes, gene-disease association, tissue specificity and gene functions subdivided into categories (e.g., diseases, tissues or functional pathways. Twenty-three genes were common to all three disorders and mapped to nine biological Superpathways including Circadian entrainment (10 genes, score = 37.0, Amphetamine addiction (five genes, score = 24.2, and Sudden infant death syndrome (six genes, score = 24.1. Brain tissues included the medulla oblongata (11 genes, score = 2.1, thalamus (10 genes, score = 2.0 and hypothalamus (nine genes, score = 2.0 with six common genes (BDNF, DRD2, CHRNA7, HTR2A, SLC6A3, and TPH2. Overlapping genes impacted dopamine and serotonin homeostasis and signal transduction pathways, impacting mood, behavior and physical activity level. Converging effects on pathways governing circadian rhythms support a core etiological relationship between neuropsychiatric illnesses and sleep disruption with hypoxia and central brain stem dysfunction.

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

    Science.gov (United States)

    Yang, Yunlai; Arouri, Khaled

    2016-03-11

    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.

  17. Excitation methods for energy dispersive analysis

    International Nuclear Information System (INIS)

    Jaklevic, J.M.

    1976-01-01

    The rapid development in recent years of energy dispersive x-ray fluorescence analysis has been based primarily on improvements in semiconductor detector x-ray spectrometers. However, the whole analysis system performance is critically dependent on the availability of optimum methods of excitation for the characteristic x rays in specimens. A number of analysis facilities based on various methods of excitation have been developed over the past few years. A discussion is given of the features of various excitation methods including charged particles, monochromatic photons, and broad-energy band photons. The effects of the excitation method on background and sensitivity are discussed from both theoretical and experimental viewpoints. Recent developments such as pulsed excitation and polarized photons are also discussed

  18. Cost-effectiveness analysis of a postoperative clinical care pathway in head and neck surgery with microvascular reconstruction

    OpenAIRE

    Dautremont, Jonathan F; Rudmik, Luke R; Yeung, Justin; Asante, Tiffany; Nakoneshny, Steve C; Hoy, Monica; Lui, Amanda; Chandarana, Shamir P; Matthews, Thomas W; Schrag, Christiaan; Dort, Joseph C

    2013-01-01

    Background The objective of this study is to evaluate the cost-effectiveness of a postoperative clinical care pathway for patients undergoing major head and neck oncologic surgery with microvascular reconstruction. Methods This is a comparative trial of a prospective treatment group managed on a postoperative clinical care pathway and a historical group managed prior to pathway implementation. Effectiveness outcomes evaluated were total hospital days, return to OR, readmission to ICU and rate...

  19. Uncertainty and sensitivity analysis of food pathway results with the MACCS Reactor Accident Consequence Model

    International Nuclear Information System (INIS)

    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

  20. Uncertainty and sensitivity analysis of food pathway results with the MACCS reactor accident consequence model

    International Nuclear Information System (INIS)

    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

  1. Instrumental methods of analysis, 7th edition

    International Nuclear Information System (INIS)

    Willard, H.H.; Merritt, L.L. Jr.; Dean, J.A.; Settle, F.A. Jr.

    1988-01-01

    The authors have prepared an organized and generally polished product. The book is fashioned to be used as a textbook for an undergraduate instrumental analysis course, a supporting textbook for graduate-level courses, and a general reference work on analytical instrumentation and techniques for professional chemists. Four major areas are emphasized: data collection and processing, spectroscopic instrumentation and methods, liquid and gas chromatographic methods, and electrochemical methods. Analytical instrumentation and methods have been updated, and a thorough citation of pertinent recent literature is included

  2. Identification of key genes and pathways associated with neuropathic pain in uninjured dorsal root ganglion by using bioinformatic analysis

    Directory of Open Access Journals (Sweden)

    Chen CJ

    2017-11-01

    Full Text Available Chao-Jin Chen,* De-Zhao Liu,* Wei-Feng Yao, Yu Gu, Fei Huang, Zi-Qing Hei, Xiang Li Department of Anesthesiology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, People’s Republic of China *These authors contributed equally to this work Purpose: Neuropathic pain is a complex chronic condition occurring post-nervous system damage. The transcriptional reprogramming of injured dorsal root ganglia (DRGs drives neuropathic pain. However, few comparative analyses using high-throughput platforms have investigated uninjured DRG in neuropathic pain, and potential interactions among differentially expressed genes (DEGs and pathways were not taken into consideration. The aim of this study was to identify changes in genes and pathways associated with neuropathic pain in uninjured L4 DRG after L5 spinal nerve ligation (SNL by using bioinformatic analysis.Materials and methods: The microarray profile GSE24982 was downloaded from the Gene Expression Omnibus database to identify DEGs between DRGs in SNL and sham rats. The prioritization for these DEGs was performed using the Toppgene database followed by gene ontology and pathway enrichment analyses. The relationships among DEGs from the protein interactive perspective were analyzed using protein–protein interaction (PPI network and module analysis. Real-time polymerase chain reaction (PCR and Western blotting were used to confirm the expression of DEGs in the rodent neuropathic pain model.Results: A total of 206 DEGs that might play a role in neuropathic pain were identified in L4 DRG, of which 75 were upregulated and 131 were downregulated. The upregulated DEGs were enriched in biological processes related to transcription regulation and molecular functions such as DNA binding, cell cycle, and the FoxO signaling pathway. Ctnnb1 protein had the highest connectivity degrees in the PPI network. The in vivo studies also validated that mRNA and protein levels of Ctnnb1 were

  3. Assembly of inflammation-related genes for pathway-focused genetic analysis.

    Directory of Open Access Journals (Sweden)

    Matthew J Loza

    2007-10-01

    Full Text Available Recent identifications of associations between novel variants in inflammation-related genes and several common diseases emphasize the need for systematic evaluations of these genes in disease susceptibility. Considering that many genes are involved in the complex inflammation responses and many genetic variants in these genes have the potential to alter the functions and expression of these genes, we assembled a list of key inflammation-related genes to facilitate the identification of genetic associations of diseases with an inflammation-related etiology. We first reviewed various phases of inflammation responses, including the development of immune cells, sensing of danger, influx of cells to sites of insult, activation and functional responses of immune and non-immune cells, and resolution of the immune response. Assisted by the Ingenuity Pathway Analysis, we then identified 17 functional sub-pathways that are involved in one or multiple phases. This organization would greatly increase the chance of detecting gene-gene interactions by hierarchical clustering of genes with their functional closeness in a pathway. Finally, as an example application, we have developed tagging single nucleotide polymorphism (tSNP arrays for populations of European and African descent to capture all the common variants of these key inflammation-related genes. Assays of these tSNPs have been designed and assembled into two Affymetrix ParAllele customized chips, one each for European (12,011 SNPs and African (21,542 SNPs populations. These tSNPs have greater coverage for these inflammation-related genes compared to the existing genome-wide arrays, particularly in the African population. These tSNP arrays can facilitate systematic evaluation of inflammation pathways in disease susceptibility. For additional applications, other genotyping platforms could also be employed. For existing genome-wide association data, this list of key inflammation-related genes and

  4. Functional pathway analysis of genes associated with response to treatment for chronic hepatitis C.

    Science.gov (United States)

    Birerdinc, A; Afendy, A; Stepanova, M; Younossi, I; Manyam, G; Baranova, A; Younossi, Z M

    2010-10-01

    Chronic hepatitis C (CH-C) is among the most common causes of chronic liver disease. Approximately 50% of patients with CH-C treated with pegylated interferon-α and ribavirin (PEG-IFN-α + RBV) achieve a sustained virological response (SVR). Several factors such as genotype 1, African American (AA) race, obesity and the absence of an early virological response (EVR) are associated with low SVR. This study elucidates molecular pathways deregulated in patients with CH-C with negative predictors of response to antiviral therapy. Sixty-eight patients with CH-C who underwent a full course of treatment with PEG-IFN-α + RBV were included in the study. Pretreatment blood samples were collected in PAXgene™ RNA tubes. EVR, complete EVR (cEVR), and SVR rates were 76%, 57% and 41%, respectively. Total RNA was extracted from pretreatment peripheral blood mononuclear cells, quantified and used for one-step RT-PCR to profile 154 mRNAs. The expression of mRNAs was normalized with six 'housekeeping' genes. Differentially expressed genes were separated into up and downregulated gene lists according to the presence or absence of a risk factor and subjected to KEGG Pathway Painter which allows high-throughput visualization of the pathway-specific changes in expression profiles. The genes were consolidated into the networks associated with known predictors of response. Before treatment, various genes associated with core components of the JAK/STAT pathway were activated in the cohorts least likely to achieve SVR. Genes related to focal adhesion and TGF-β pathways were activated in some patients with negative predictors of response. Pathway-centred analysis of gene expression profiles from treated patients with CH-C points to the Janus kinase-signal transducers and activators of transcription signalling cascade as the major pathogenetic component responsible for not achieving SVR. In addition, focal adhesion and TGF-β pathways are associated with some predictors of response.

  5. Thermodynamics of metabolic pathways for penicillin production: Analysis of thermodynamic feasibility and free energy changes during fed-batch cultivation

    DEFF Research Database (Denmark)

    Pissarra, P.D.; Nielsen, Jens Bredal

    1997-01-01

    This paper describes the thermodynamic analysis of pathways related to penicillin production in Penicillium chrysogenum. First a thermodynamic feasibility analysis is performed of the L-lysine pathway of which one of the precursors for penicillin biosynthesis (alpha-aminoadipic acid......) is an intermediate. It is found that the L-lysine pathway in P. chrysogenum is thermodynamically feasible and that the calculated standard Gibbs free energy values of the two enzymes controlling the pathway flux indicate that they operate far from equilibrium. It is therefore proposed that the regulation of alpha......-aminoadipate reductase by lysine is important to maintain a high concentration of alpha-aminoadipate in order to direct the carbon flux to penicillin production. Secondly the changes in Gibbs free energy in the penicillin biosynthetic pathway during fed-batch cultivation were studied. The analysis showed that all...

  6. Integrating eQTL data with GWAS summary statistics in pathway-based analysis with application to schizophrenia.

    Science.gov (United States)

    Wu, Chong; Pan, Wei

    2018-04-01

    Many genetic variants affect complex traits through gene expression, which can be exploited to boost statistical power and enhance interpretation in genome-wide association studies (GWASs) as demonstrated by the transcriptome-wide association study (TWAS) approach. Furthermore, due to polygenic inheritance, a complex trait is often affected by multiple genes with similar functions as annotated in gene pathways. Here, we extend TWAS from gene-based analysis to pathway-based analysis: we integrate public pathway collections, expression quantitative trait locus (eQTL) data and GWAS summary association statistics (or GWAS individual-level data) to identify gene pathways associated with complex traits. The basic idea is to weight the SNPs of the genes in a pathway based on their estimated cis-effects on gene expression, then adaptively test for association of the pathway with a GWAS trait by effectively aggregating possibly weak association signals across the genes in the pathway. The P values can be calculated analytically and thus fast. We applied our proposed test with the KEGG and GO pathways to two schizophrenia (SCZ) GWAS summary association data sets, denoted by SCZ1 and SCZ2 with about 20,000 and 150,000 subjects, respectively. Most of the significant pathways identified by analyzing the SCZ1 data were reproduced by the SCZ2 data. Importantly, we identified 15 novel pathways associated with SCZ, such as GABA receptor complex (GO:1902710), which could not be uncovered by the standard single SNP-based analysis or gene-based TWAS. The newly identified pathways may help us gain insights into the biological mechanism underlying SCZ. Our results showcase the power of incorporating gene expression information and gene functional annotations into pathway-based association testing for GWAS. © 2018 WILEY PERIODICALS, INC.

  7. Novel degradation pathway and kinetic analysis for buprofezin removal by newly isolated Bacillus sp.

    Science.gov (United States)

    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. Copyright © 2016 Elsevier Ltd. All rights reserved.

  8. Metabolomics coupled with multivariate data and pathway analysis on potential biomarkers in cholestasis and intervention effect of Paeonia lactiflora Pall.

    Directory of Open Access Journals (Sweden)

    Xiao eMa

    2016-02-01

    Full Text Available Background: The dried root of Paeonia lactiflora Pall. (PLP is a classical Chinese herbal medicine that has been used to treat hepatic disease for thousands of years. Our previous work suggested that PLP can be used to treat hepatitis with severe cholestasis. This study explored the mechanism by which PLP affects ANIT-induced cholestasis in rats using a metabolomics approach.Methods: The effects of PLP on serum indices (TBIL, DBIL, AST, ALT, ALP and TBA and the histopathology of the liver were analyzed. Moreover, UHPLC-Q-TOF was performed to identify the possible effect of PLP on metabolites. The pathway analysis was conducted to illustrate the pathways and network by which PLP treats cholestasis. Result: High-dose PLP remarkably down-regulated the serum indices and alleviated histological damage to the liver. Metabolomics analyses showed that the therapeutic effect of high-dose PLP is mainly associated with the regulation of several metabolites, such as glycocholic acid, taurocholic acid, glycochenodeoxycholic acid, L(D-arginine and L-tryptophan. A pathway analysis showed that the metabolites were related to bile acid secretion and amino acid metabolism. In addition, the significant changes in bile acid transporters also indicated that bile acid metabolism might be involved in the therapeutic effect of PLP on cholestasis. Moreover, a principal component analysis indicated that the metabolites in the high-dose PLP group were closer to those of the control, whereas those of the moderate dose or low-dose PLP group were closer to those of the ANIT group. This finding indicated that metabolites may be responsible for the differences between the effects of low-dose and moderate-dose PLP. Conclusions: The therapeutic effect of high-dose PLP on cholestasis is possibly related to regulation of bile acid secretion and amino acid metabolism. Moreover, these findings may help better understand the mechanisms of disease and provide a potential therapy for

  9. Gene expression profiling, pathway analysis and subtype classification reveal molecular heterogeneity in hepatocellular carcinoma and suggest subtype specific therapeutic targets.

    Science.gov (United States)

    Agarwal, Rahul; Narayan, Jitendra; Bhattacharyya, Amitava; Saraswat, Mayank; Tomar, Anil Kumar

    2017-10-01

    A very low 5-year survival rate among hepatocellular carcinoma (HCC) patients is mainly due to lack of early stage diagnosis, distant metastasis and high risk of postoperative recurrence. Hence ascertaining novel biomarkers for early diagnosis and patient specific therapeutics is crucial and urgent. Here, we have performed a comprehensive analysis of the expression data of 423 HCC patients (373 tumors and 50 controls) downloaded from The Cancer Genome Atlas (TCGA) followed by pathway enrichment by gene ontology annotations, subtype classification and overall survival analysis. The differential gene expression analysis using non-parametric Wilcoxon test revealed a total of 479 up-regulated and 91 down-regulated genes in HCC compared to controls. The list of top differentially expressed genes mainly consists of tumor/cancer associated genes, such as AFP, THBS4, LCN2, GPC3, NUF2, etc. The genes over-expressed in HCC were mainly associated with cell cycle pathways. In total, 59 kinases associated genes were found over-expressed in HCC, including TTK, MELK, BUB1, NEK2, BUB1B, AURKB, PLK1, CDK1, PKMYT1, PBK, etc. Overall four distinct HCC subtypes were predicted using consensus clustering method. Each subtype was unique in terms of gene expression, pathway enrichment and median survival. Conclusively, this study has exposed a number of interesting genes which can be exploited in future as potential markers of HCC, diagnostic as well as prognostic and subtype classification may guide for improved and specific therapy. Copyright © 2017 Elsevier Inc. All rights reserved.

  10. [Analysis on "component-target-pathway" of Paeonia lactiflora in treating cardiac diseases based on data mining].

    Science.gov (United States)

    Liu, Yang; Zhang, Fang-Bo; Tang, Shi-Huan; Wang, Ping; Li, Sen; Su, Jin; Zhou, Rong-Rong; Zhang, Jia-Qi; Sun, Hui-Feng

    2018-04-01

    Based on the literature review and modern application of Paeonia lactiflora in heart diseases, this article would predict the target of drug and disease by intergrative pharmacology platform of traditional Chinese medicine (TCMIP, http://www.tcmip.cn), and then explore the molecular mechanism of P. lactiflora in treatment of heart disease, providing theoretical basis and method for further studies on P. lactiflora. According to the ancient books, P. lactiflora with functions of "removing the vascular obstruction, removing the lumps, relieving pain, diuretic, nutrient qi" and other effects, have been used for many times to treat heart disease. Some prescriptions are also favored by the modern physicians nowadays. With the development of science, the chemical components that play a role in heart disease and the interrelation between these components and the body become the research hotspot. In order to further reveal the pharmacological substance base and molecular mechanism of P. lactiflora for the treatment of such diseases, TCM-IP was used to obtain multiple molecular targets and signaling pathways in treatment of heart disease. ATP1A1, a common target of drug and disease, was related to energy, and HDAC2 mainly regulated cardiomyocyte hypertrophy gene and cardiomyocyte expression. Other main drug targets such as GCK, CHUK and PRKAA2 indirectly regulated heart disease through many pathways; multiple disease-associated signaling pathways interfered with various heart diseases including coronary heart disease, myocardial ischemia and myocardial hypertrophy through influencing energy metabolism, enzyme activity and gene expression. In conclusion, P. lactiflora plays a role in protecting heart function by regulating the gene expression of cardiomyocytes directly. Meanwhile, it can indirectly intervene in other pathways of heart function, and thus participate in the treatment of heart disease. In this paper, the molecular mechanism of P. lactiflora for treatment of

  11. Limitations of systemic accident analysis methods

    Directory of Open Access Journals (Sweden)

    Casandra Venera BALAN

    2016-12-01

    Full Text Available In terms of system theory, the description of complex accidents is not limited to the analysis of the sequence of events / individual conditions, but highlights nonlinear functional characteristics and frames human or technical performance in relation to normal functioning of the system, in safety conditions. Thus, the research of the system entities as a whole is no longer an abstraction of a concrete situation, but an exceeding of the theoretical limits set by analysis based on linear methods. Despite the issues outlined above, the hypothesis that there isn’t a complete method for accident analysis is supported by the nonlinearity of the considered function or restrictions, imposing a broad vision of the elements introduced in the analysis, so it can identify elements corresponding to nominal parameters or trigger factors.

  12. Application of Software Safety Analysis Methods

    International Nuclear Information System (INIS)

    Park, G. Y.; Hur, S.; Cheon, S. W.; Kim, D. H.; Lee, D. Y.; Kwon, K. C.; Lee, S. J.; Koo, Y. H.

    2009-01-01

    A fully digitalized reactor protection system, which is called the IDiPS-RPS, was developed through the KNICS project. The IDiPS-RPS has four redundant and separated channels. Each channel is mainly composed of a group of bistable processors which redundantly compare process variables with their corresponding setpoints and a group of coincidence processors that generate a final trip signal when a trip condition is satisfied. Each channel also contains a test processor called the ATIP and a display and command processor called the COM. All the functions were implemented in software. During the development of the safety software, various software safety analysis methods were applied, in parallel to the verification and validation (V and V) activities, along the software development life cycle. The software safety analysis methods employed were the software hazard and operability (Software HAZOP) study, the software fault tree analysis (Software FTA), and the software failure modes and effects analysis (Software FMEA)

  13. Spatial analysis statistics, visualization, and computational methods

    CERN Document Server

    Oyana, Tonny J

    2015-01-01

    An introductory text for the next generation of geospatial analysts and data scientists, Spatial Analysis: Statistics, Visualization, and Computational Methods focuses on the fundamentals of spatial analysis using traditional, contemporary, and computational methods. Outlining both non-spatial and spatial statistical concepts, the authors present practical applications of geospatial data tools, techniques, and strategies in geographic studies. They offer a problem-based learning (PBL) approach to spatial analysis-containing hands-on problem-sets that can be worked out in MS Excel or ArcGIS-as well as detailed illustrations and numerous case studies. The book enables readers to: Identify types and characterize non-spatial and spatial data Demonstrate their competence to explore, visualize, summarize, analyze, optimize, and clearly present statistical data and results Construct testable hypotheses that require inferential statistical analysis Process spatial data, extract explanatory variables, conduct statisti...

  14. Advanced analysis methods in particle physics

    Energy Technology Data Exchange (ETDEWEB)

    Bhat, Pushpalatha C.; /Fermilab

    2010-10-01

    Each generation of high energy physics experiments is grander in scale than the previous - more powerful, more complex and more demanding in terms of data handling and analysis. The spectacular performance of the Tevatron and the beginning of operations of the Large Hadron Collider, have placed us at the threshold of a new era in particle physics. The discovery of the Higgs boson or another agent of electroweak symmetry breaking and evidence of new physics may be just around the corner. The greatest challenge in these pursuits is to extract the extremely rare signals, if any, from huge backgrounds arising from known physics processes. The use of advanced analysis techniques is crucial in achieving this goal. In this review, I discuss the concepts of optimal analysis, some important advanced analysis methods and a few examples. The judicious use of these advanced methods should enable new discoveries and produce results with better precision, robustness and clarity.

  15. Comprehensive analysis of schizophrenia-associated loci highlights ion channel pathways and biologically plausible candidate causal genes

    DEFF Research Database (Denmark)

    Pers, Tune H; Timshel, Pascal; Ripke, Stephan

    2016-01-01

    Over 100 associated genetic loci have been robustly associated with schizophrenia. Gene prioritization and pathway analysis have focused on a priori hypotheses and thus may have been unduly influenced by prior assumptions and missed important causal genes and pathways. Using a data-driven approac...

  16. Acquisition/Diversion Pathway Analysis of the DUPIC Fuel Cycle for the Assessment of Proliferation Resistance

    International Nuclear Information System (INIS)

    Chang, Hong Lae; Ko, Won Il

    2008-01-01

    Within the International Project on Innovative Nuclear Reactors and Fuel Cycles (INPRO) of the IAEA, a methodology for evaluating proliferation resistance (INPRO PR methodology) has been developed in order to provide guidance in using the INPRO methodology. However, it remains to develop the methodology to evaluate User Requirements (UR) 4 regarding multiplicity and robustness of barriers against proliferation (innovative nuclear energy systems should incorporate multiple proliferation resistance features and measures). To develop the assessment procedure and metrics for User Requirement 4 (UR4), the coarse acquisition/ diversion pathway analysis of the DUPIC Fuel Cycle has been performed. The most plausible pathways for the acquisition of weapons-usable nuclear material were identified and analyzed using a systematic approach herein, and future work to complete the assessment approach for the UR4 of the INPRO methodology regarding the multiplicity and robustness of barriers against proliferation are also proposed

  17. Review of strain buckling: analysis methods

    International Nuclear Information System (INIS)

    Moulin, D.

    1987-01-01

    This report represents an attempt to review the mechanical analysis methods reported in the literature to account for the specific behaviour that we call buckling under strain. In this report, this expression covers all buckling mechanisms in which the strains imposed play a role, whether they act alone (as in simple buckling under controlled strain), or whether they act with other loadings (primary loading, such as pressure, for example). Attention is focused on the practical problems relevant to LMFBR reactors. The components concerned are distinguished by their high slenderness ratios and by rather high thermal levels, both constant and variable with time. Conventional static buckling analysis methods are not always appropriate for the consideration of buckling under strain. New methods must therefore be developed in certain cases. It is also hoped that this review will facilitate the coding of these analytical methods to aid the constructor in his design task and to identify the areas which merit further investigation

  18. Analysis of mixed data methods & applications

    CERN Document Server

    de Leon, Alexander R

    2013-01-01

    A comprehensive source on mixed data analysis, Analysis of Mixed Data: Methods & Applications summarizes the fundamental developments in the field. Case studies are used extensively throughout the book to illustrate interesting applications from economics, medicine and health, marketing, and genetics. Carefully edited for smooth readability and seamless transitions between chaptersAll chapters follow a common structure, with an introduction and a concluding summary, and include illustrative examples from real-life case studies in developmental toxicolog

  19. Scope-Based Method Cache Analysis

    DEFF Research Database (Denmark)

    Huber, Benedikt; Hepp, Stefan; Schoeberl, Martin

    2014-01-01

    The quest for time-predictable systems has led to the exploration of new hardware architectures that simplify analysis and reasoning in the temporal domain, while still providing competitive performance. For the instruction memory, the method cache is a conceptually attractive solution, as it req......The quest for time-predictable systems has led to the exploration of new hardware architectures that simplify analysis and reasoning in the temporal domain, while still providing competitive performance. For the instruction memory, the method cache is a conceptually attractive solution...

  20. Quantitative analysis method for ship construction quality

    Directory of Open Access Journals (Sweden)

    FU Senzong

    2017-03-01

    Full Text Available The excellent performance of a ship is assured by the accurate evaluation of its construction quality. For a long time, research into the construction quality of ships has mainly focused on qualitative analysis due to a shortage of process data, which results from limited samples, varied process types and non-standardized processes. Aiming at predicting and controlling the influence of the construction process on the construction quality of ships, this article proposes a reliability quantitative analysis flow path for the ship construction process and fuzzy calculation method. Based on the process-quality factor model proposed by the Function-Oriented Quality Control (FOQC method, we combine fuzzy mathematics with the expert grading method to deduce formulations calculating the fuzzy process reliability of the ordinal connection model, series connection model and mixed connection model. The quantitative analysis method is applied in analyzing the process reliability of a ship's shaft gear box installation, which proves the applicability and effectiveness of the method. The analysis results can be a useful reference for setting key quality inspection points and optimizing key processes.

  1. A Hypothesis for Using Pathway Genetic Load Analysis for Understanding Complex Outcomes in Bilirubin Encephalopathy

    Science.gov (United States)

    Riordan, Sean M.; Bittel, Douglas C.; Le Pichon, Jean-Baptiste; Gazzin, Silvia; Tiribelli, Claudio; Watchko, Jon F.; Wennberg, Richard P.; Shapiro, Steven M.

    2016-01-01

    Genetic-based susceptibility to bilirubin neurotoxicity and chronic bilirubin encephalopathy (kernicterus) is still poorly understood. Neonatal jaundice affects 60–80% of newborns, and considerable effort goes into preventing this relatively benign condition from escalating into the development of kernicterus making the incidence of this potentially devastating condition very rare in more developed countries. The current understanding of the genetic background of kernicterus is largely comprised of mutations related to alterations of bilirubin production, elimination, or both. Less is known about mutations that may predispose or protect against CNS bilirubin neurotoxicity. The lack of a monogenetic source for this risk of bilirubin neurotoxicity suggests that disease progression is dependent upon an overall decrease in the functionality of one or more essential genetically controlled metabolic pathways. In other words, a “load” is placed on key pathways in the form of multiple genetic variants that combine to create a vulnerable phenotype. The idea of epistatic interactions creating a pathway genetic load (PGL) that affects the response to a specific insult has been previously reported as a PGL score. We hypothesize that the PGL score can be used to investigate whether increased susceptibility to bilirubin-induced CNS damage in neonates is due to a mutational load being placed on key genetic pathways important to the central nervous system's response to bilirubin neurotoxicity. We propose a modification of the PGL score method that replaces the use of a canonical pathway with custom gene lists organized into three tiers with descending levels of evidence combined with the utilization of single nucleotide polymorphism (SNP) causality prediction methods. The PGL score has the potential to explain the genetic background of complex bilirubin induced neurological disorders (BIND) such as kernicterus and could be the key to understanding ranges of outcome severity

  2. Piping dynamic analysis by the synthesis method

    International Nuclear Information System (INIS)

    Bezler, P.; Curreri, J.R.

    1976-01-01

    Since piping systems are a frequent source of noise and vibrations, their efficient dynamic analysis is imperative. As an alternate to more conventional analyses methods, an application of the synthesis method to piping vibrations analyses is demonstrated. Specifically, the technique is illustrated by determining the normal modes and natural frequencies of a composite bend from the normal mode and natural frequency data of two component parts. A comparison of the results to those derived for the composite bend by other techniques is made

  3. Probabilistic Analysis Methods for Hybrid Ventilation

    DEFF Research Database (Denmark)

    Brohus, Henrik; Frier, Christian; Heiselberg, Per

    This paper discusses a general approach for the application of probabilistic analysis methods in the design of ventilation systems. The aims and scope of probabilistic versus deterministic methods are addressed with special emphasis on hybrid ventilation systems. A preliminary application...... of stochastic differential equations is presented comprising a general heat balance for an arbitrary number of loads and zones in a building to determine the thermal behaviour under random conditions....

  4. Consortium analysis of gene and gene–folate interactions in purine and pyrimidine metabolism pathways with ovarian carcinoma risk

    DEFF Research Database (Denmark)

    Kelemen, Linda E; Terry, Kathryn L; Goodman, Marc T

    2014-01-01

    SCOPE: We reevaluated previously reported associations between variants in pathways of one-carbon (1-C) (folate) transfer genes and ovarian carcinoma (OC) risk, and in related pathways of purine and pyrimidine metabolism, and assessed interactions with folate intake. METHODS AND RESULTS: Odds rat...

  5. Pathways analysis and radiation-dose estimates for radioactive residues at formerly utilized MED/AEC sites

    International Nuclear Information System (INIS)

    Gilbert, T.L.; Chee, P.C.; Knight, M.J.; Peterson, J.M.; Roberts, C.J.; Robinson, J.E.; Tsai, S.Y.H.; Yuan, Y.C.

    1983-03-01

    Methods of analysis are developed for estimating the largest individual radiation dose that could result from residual radioactivity at sites identified by the Formerly Utilized Sites Remedial Action Program (FUSRAP) of the US Department of Energy. Two unique aspects of the methods are (1) a systematic structuring of the radiation pathways analysis into source terms, source-to-exposure analysis, and exposure-to-dose analysis, and (2) the systematic use of data on the average concentrations of naturally occurring radionuclides in soil, food, and the human body in order to assess the validity of model calculations and obtain more realistic values. The methods are applied to a typical FUSRAP site in order to obtain generic source-to-dose (D/S) conversion factors for estimating the radiation dose to the maximally exposed individual from a known concentration of radionuclides in the soil. The D/S factors are used to derive soil guidelines, i.e., the limiting concentrations of radionuclides at a typical FUSRAP site that are unlikely to result in individual dose limits that exceed generally accepted radiation protection standards. The results lead to the conclusion that the soil guidelines should not exceed 17, 75, and 300 pCi/g for Ra-226, U-238, and Th-230, respectively

  6. Pathways analysis and radiation-dose estimates for radioactive residues at formerly utilized MED/AEC sites

    Energy Technology Data Exchange (ETDEWEB)

    Gilbert, T.L.; Chee, P.C.; Knight, M.J.; Peterson, J.M.; Roberts, C.J.; Robinson, J.E.; Tsai, S.Y.H.; Yuan, Y.C.

    1983-03-01

    Methods of analysis are developed for estimating the largest individual radiation dose that could result from residual radioactivity at sites identified by the Formerly Utilized Sites Remedial Action Program (FUSRAP) of the US Department of Energy. Two unique aspects of the methods are (1) a systematic structuring of the radiation pathways analysis into source terms, source-to-exposure analysis, and exposure-to-dose analysis, and (2) the systematic use of data on the average concentrations of naturally occurring radionuclides in soil, food, and the human body in order to assess the validity of model calculations and obtain more realistic values. The methods are applied to a typical FUSRAP site in order to obtain generic source-to-dose (D/S) conversion factors for estimating the radiation dose to the maximally exposed individual from a known concentration of radionuclides in the soil. The D/S factors are used to derive soil guidelines, i.e., the limiting concentrations of radionuclides at a typical FUSRAP site that are unlikely to result in individual dose limits that exceed generally accepted radiation protection standards. The results lead to the conclusion that the soil guidelines should not exceed 17, 75, and 300 pCi/g for Ra-226, U-238, and Th-230, respectively.

  7. Pathway-based analyses.

    Science.gov (United States)

    Kent, Jack W

    2016-02-03

    New technologies for acquisition of genomic data, while offering unprecedented opportunities for genetic discovery, also impose severe burdens of interpretation and penalties for multiple testing. The Pathway-based Analyses Group of the Genetic Analysis Workshop 19 (GAW19) sought reduction of multiple-testing burden through various approaches to aggregation of highdimensional data in pathways informed by prior biological knowledge. Experimental methods testedincluded the use of "synthetic pathways" (random sets of genes) to estimate power and false-positive error rate of methods applied to simulated data; data reduction via independent components analysis, single-nucleotide polymorphism (SNP)-SNP interaction, and use of gene sets to estimate genetic similarity; and general assessment of the efficacy of prior biological knowledge to reduce the dimensionality of complex genomic data. The work of this group explored several promising approaches to managing high-dimensional data, with the caveat that these methods are necessarily constrained by the quality of external bioinformatic annotation.

  8. Chemical analysis by nuclear methods. v. 2

    International Nuclear Information System (INIS)

    Alfassi, Z.B.

    1998-01-01

    'Chemical analysis by Nuclear Methods' is an effort of some renowned authors in field of nuclear chemistry and radiochemistry which is compiled by Alfassi, Z.B. and translated into Farsi version collected in two volumes. The second volume consists of the following chapters: Detecting ion recoil scattering and elastic scattering are dealt in the eleventh chapter, the twelfth chapter is devoted to nuclear reaction analysis using charged particles, X-ray emission is discussed at thirteenth chapter, the fourteenth chapter is about using ion microprobes, X-ray fluorescence analysis is discussed in the fifteenth chapter, alpha, beta and gamma ray scattering in chemical analysis are dealt in chapter sixteen, Moessbauer spectroscopy and positron annihilation are discussed in chapter seventeen and eighteen; The last two chapters are about isotope dilution analysis and radioimmunoassay

  9. Numerical methods in software and analysis

    CERN Document Server

    Rice, John R

    1992-01-01

    Numerical Methods, Software, and Analysis, Second Edition introduces science and engineering students to the methods, tools, and ideas of numerical computation. Introductory courses in numerical methods face a fundamental problem-there is too little time to learn too much. This text solves that problem by using high-quality mathematical software. In fact, the objective of the text is to present scientific problem solving using standard mathematical software. This book discusses numerous programs and software packages focusing on the IMSL library (including the PROTRAN system) and ACM Algorithm

  10. Nonlinear structural analysis using integrated force method

    Indian Academy of Sciences (India)

    A new formulation termed the Integrated Force Method (IFM) was proposed by Patnaik ... nated ``Structure (nY m)'' where (nY m) are the force and displacement degrees of ..... Patnaik S N, Yadagiri S 1976 Frequency analysis of structures.

  11. Modern methods of wine quality analysis

    Directory of Open Access Journals (Sweden)

    Галина Зуфарівна Гайда

    2015-06-01

    Full Text Available  In this paper physical-chemical and enzymatic methods of quantitative analysis of the basic wine components were reviewed. The results of own experiments were presented for the development of enzyme- and cell-based amperometric sensors on ethanol, lactate, glucose, arginine

  12. Multiple predictor smoothing methods for sensitivity analysis

    International Nuclear Information System (INIS)

    Helton, Jon Craig; Storlie, Curtis B.

    2006-01-01

    The use of multiple predictor smoothing methods in sampling-based sensitivity analyses of complex models is investigated. Specifically, sensitivity analysis procedures based on smoothing methods employing the stepwise application of the following nonparametric regression techniques are described: (1) locally weighted regression (LOESS), (2) additive models, (3) projection pursuit regression, and (4) recursive partitioning regression. The indicated procedures are illustrated with both simple test problems and results from a performance assessment for a radioactive waste disposal facility (i.e., the Waste Isolation Pilot Plant). As shown by the example illustrations, the use of smoothing procedures based on nonparametric regression techniques can yield more informative sensitivity analysis results than can be obtained with more traditional sensitivity analysis procedures based on linear regression, rank regression or quadratic regression when nonlinear relationships between model inputs and model predictions are present

  13. Economic analysis of alternative LLW disposal methods

    International Nuclear Information System (INIS)

    Foutes, C.E.

    1987-01-01

    The Environmental Protection Agency (EPA) has evaluated the costs and benefits of alternative disposal technologies as part of its program to develop generally applicable environmental standards for the land disposal of low-level radioactive waste (LLW). Costs, population health effects and Critical Population Group (CPG) exposures resulting from alternative waste treatment and disposal methods were developed and input into the analysis. The cost-effectiveness analysis took into account a number of waste streams, hydrogeologic and climatic region settings, and waste treatment and disposal methods. Total costs of each level of a standard included costs for packaging, processing, transportation, and burial of waste. Benefits are defined in terms of reductions in the general population health risk (expected fatal cancers and genetic effects) evaluated over 10,000 years. A cost-effectiveness ratio, was calculated for each alternative standard. This paper describes the alternatives considered and preliminary results of the cost-effectiveness analysis

  14. Reliability and risk analysis methods research plan

    International Nuclear Information System (INIS)

    1984-10-01

    This document presents a plan for reliability and risk analysis methods research to be performed mainly by the Reactor Risk Branch (RRB), Division of Risk Analysis and Operations (DRAO), Office of Nuclear Regulatory Research. It includes those activities of other DRAO branches which are very closely related to those of the RRB. Related or interfacing programs of other divisions, offices and organizations are merely indicated. The primary use of this document is envisioned as an NRC working document, covering about a 3-year period, to foster better coordination in reliability and risk analysis methods development between the offices of Nuclear Regulatory Research and Nuclear Reactor Regulation. It will also serve as an information source for contractors and others to more clearly understand the objectives, needs, programmatic activities and interfaces together with the overall logical structure of the program

  15. Multiple predictor smoothing methods for sensitivity analysis.

    Energy Technology Data Exchange (ETDEWEB)

    Helton, Jon Craig; Storlie, Curtis B.

    2006-08-01

    The use of multiple predictor smoothing methods in sampling-based sensitivity analyses of complex models is investigated. Specifically, sensitivity analysis procedures based on smoothing methods employing the stepwise application of the following nonparametric regression techniques are described: (1) locally weighted regression (LOESS), (2) additive models, (3) projection pursuit regression, and (4) recursive partitioning regression. The indicated procedures are illustrated with both simple test problems and results from a performance assessment for a radioactive waste disposal facility (i.e., the Waste Isolation Pilot Plant). As shown by the example illustrations, the use of smoothing procedures based on nonparametric regression techniques can yield more informative sensitivity analysis results than can be obtained with more traditional sensitivity analysis procedures based on linear regression, rank regression or quadratic regression when nonlinear relationships between model inputs and model predictions are present.

  16. Spectroscopic Chemical Analysis Methods and Apparatus

    Science.gov (United States)

    Hug, William F. (Inventor); Reid, Ray D. (Inventor); Bhartia, Rohit (Inventor); Lane, Arthur L. (Inventor)

    2018-01-01

    Spectroscopic chemical analysis methods and apparatus are disclosed which employ deep ultraviolet (e.g. in the 200 nm to 300 nm spectral range) electron beam pumped wide bandgap semiconductor lasers, incoherent wide bandgap semiconductor light emitting devices, and hollow cathode metal ion lasers to perform non-contact, non-invasive detection of unknown chemical analytes. These deep ultraviolet sources enable dramatic size, weight and power consumption reductions of chemical analysis instruments. In some embodiments, Raman spectroscopic detection methods and apparatus use ultra-narrow-band angle tuning filters, acousto-optic tuning filters, and temperature tuned filters to enable ultra-miniature analyzers for chemical identification. In some embodiments Raman analysis is conducted along with photoluminescence spectroscopy (i.e. fluorescence and/or phosphorescence spectroscopy) to provide high levels of sensitivity and specificity in the same instrument.

  17. Computational methods for nuclear criticality safety analysis

    International Nuclear Information System (INIS)

    Maragni, M.G.

    1992-01-01

    Nuclear criticality safety analyses require the utilization of methods which have been tested and verified against benchmarks results. In this work, criticality calculations based on the KENO-IV and MCNP codes are studied aiming the qualification of these methods at the IPEN-CNEN/SP and COPESP. The utilization of variance reduction techniques is important to reduce the computer execution time, and several of them are analysed. As practical example of the above methods, a criticality safety analysis for the storage tubes for irradiated fuel elements from the IEA-R1 research has been carried out. This analysis showed that the MCNP code is more adequate for problems with complex geometries, and the KENO-IV code shows conservative results when it is not used the generalized geometry option. (author)

  18. Pathways of early fatherhood, marriage, and employment: a latent class growth analysis.

    Science.gov (United States)

    Dariotis, Jacinda K; Pleck, Joseph H; Astone, Nan M; Sonenstein, Freya L

    2011-05-01

    In the National Longitudinal Survey of Youth 1979 (NLSY79), young fathers include heterogeneous subgroups with varying early life pathways in terms of fatherhood timing, the timing of first marriage, and holding full-time employment. Using latent class growth analysis with 10 observations between ages 18 and 37, we derived five latent classes with median ages of first fatherhood below the cohort median (26.4), constituting distinct early fatherhood pathways representing 32.4% of NLSY men: (A) Young Married Fathers, (B) Teen Married Fathers, (C) Young Underemployed Married Fathers, (D) Young Underemployed Single Fathers, and (E) Young Later-Marrying Fathers. A sixth latent class of men who become fathers around the cohort median, following full-time employment and marriage (On-Time On-Sequence Fathers), is the comparison group. With sociodemographic background controlled, all early fatherhood pathways show disadvantage in at least some later-life circumstances (earnings, educational attainment, marital status, and incarceration). The extent of disadvantage is greater when early fatherhood occurs at relatively younger ages (before age 20), occurs outside marriage, or occurs outside full-time employment. The relative disadvantage associated with early fatherhood, unlike early motherhood, increases over the life course.

  19. RNAseq analysis reveals pathways and candidate genes associated with salinity tolerance in a spaceflight-induced wheat mutant.

    Science.gov (United States)

    Xiong, Hongchun; Guo, Huijun; Xie, Yongdun; Zhao, Linshu; Gu, Jiayu; Zhao, Shirong; Li, Junhui; Liu, Luxiang

    2017-06-02

    Salinity stress has become an increasing threat to food security worldwide and elucidation of the mechanism for salinity tolerance is of great significance. Induced mutation, especially spaceflight mutagenesis, is one important method for crop breeding. In this study, we show that a spaceflight-induced wheat mutant, named salinity tolerance 1 (st1), is a salinity-tolerant line. We report the characteristics of transcriptomic sequence variation induced by spaceflight, and show that mutations in genes associated with sodium ion transport may directly contribute to salinity tolerance in st1. Furthermore, GO and KEGG enrichment analysis of differentially expressed genes (DEGs) between salinity-treated st1 and wild type suggested that the homeostasis of oxidation-reduction process is important for salt tolerance in st1. Through KEGG pathway analysis, "Butanoate metabolism" was identified as a new pathway for salinity responses. Additionally, key genes for salinity tolerance, such as genes encoding arginine decarboxylase, polyamine oxidase, hormones-related, were not only salt-induced in st1 but also showed higher expression in salt-treated st1 compared with salt-treated WT, indicating that these genes may play important roles in salinity tolerance in st1. This study presents valuable genetic resources for studies on transcriptome variation caused by induced mutation and the identification of salt tolerance genes in crops.

  20. Combining Pathway Identification and Breast Cancer Survival Prediction via Screening-Network Methods

    Directory of Open Access Journals (Sweden)

    Antonella Iuliano

    2018-06-01

    Full Text Available Breast cancer is one of the most common invasive tumors causing high mortality among women. It is characterized by high heterogeneity regarding its biological and clinical characteristics. Several high-throughput assays have been used to collect genome-wide information for many patients in large collaborative studies. This knowledge has improved our understanding of its biology and led to new methods of diagnosing and treating the disease. In particular, system biology has become a valid approach to obtain better insights into breast cancer biological mechanisms. A crucial component of current research lies in identifying novel biomarkers that can be predictive for breast cancer patient prognosis on the basis of the molecular signature of the tumor sample. However, the high dimension and low sample size of data greatly increase the difficulty of cancer survival analysis demanding for the development of ad-hoc statistical methods. In this work, we propose novel screening-network methods that predict patient survival outcome by screening key survival-related genes and we assess the capability of the proposed approaches using METABRIC dataset. In particular, we first identify a subset of genes by using variable screening techniques on gene expression data. Then, we perform Cox regression analysis by incorporating network information associated with the selected subset of genes. The novelty of this work consists in the improved prediction of survival responses due to the different types of screenings (i.e., a biomedical-driven, data-driven and a combination of the two before building the network-penalized model. Indeed, the combination of the two screening approaches allows us to use the available biological knowledge on breast cancer and complement it with additional information emerging from the data used for the analysis. Moreover, we also illustrate how to extend the proposed approaches to integrate an additional omic layer, such as copy number

  1. Pathway Analysis of Metabolic Syndrome Using a Genome-Wide Association Study of Korea Associated Resource (KARE Cohorts

    Directory of Open Access Journals (Sweden)

    Unjin Shim

    2014-12-01

    Full Text Available Metabolic syndrome (MetS is a complex disorder related to insulin resistance, obesity, and inflammation. Genetic and environmental factors also contribute to the development of MetS, and through genome-wide association studies (GWASs, important susceptibility loci have been identified. However, GWASs focus more on individual single-nucleotide polymorphisms (SNPs, explaining only a small portion of genetic heritability. To overcome this limitation, pathway analyses are being applied to GWAS datasets. The aim of this study is to elucidate the biological pathways involved in the pathogenesis of MetS through pathway analysis. Cohort data from the Korea Associated Resource (KARE was used for analysis, which include 8,842 individuals (age, 52.2 ± 8.9 years; body mass index, 24.6 ± 3.2 kg/m2. A total of 312,121 autosomal SNPs were obtained after quality control. Pathway analysis was conducted using Meta-analysis Gene-Set Enrichment of Variant Associations (MAGENTA to discover the biological pathways associated with MetS. In the discovery phase, SNPs from chromosome 12, including rs11066280, rs2074356, and rs12229654, were associated with MetS (p < 5 × 10-6, and rs11066280 satisfied the Bonferroni-corrected cutoff (unadjusted p < 1.38 × 10-7, Bonferroni-adjusted p < 0.05. Through pathway analysis, biological pathways, including electron carrier activity, signaling by platelet-derived growth factor (PDGF, the mitogen-activated protein kinase kinase kinase cascade, PDGF binding, peroxisome proliferator-activated receptor (PPAR signaling, and DNA repair, were associated with MetS. Through pathway analysis of MetS, pathways related with PDGF, mitogen-activated protein kinase, and PPAR signaling, as well as nucleic acid binding, protein secretion, and DNA repair, were identified. Further studies will be needed to clarify the genetic pathogenesis leading to MetS.

  2. Metatranscriptomic analysis of diverse microbial communities reveals core metabolic pathways and microbiome-specific functionality.

    Science.gov (United States)

    Jiang, Yue; Xiong, Xuejian; Danska, Jayne; Parkinson, John

    2016-01-12

    Metatranscriptomics is emerging as a powerful technology for the functional characterization of complex microbial communities (microbiomes). Use of unbiased RNA-sequencing can reveal both the taxonomic composition and active biochemical functions of a complex microbial community. However, the lack of established reference genomes, computational tools and pipelines make analysis and interpretation of these datasets challenging. Systematic studies that compare data across microbiomes are needed to demonstrate the ability of such pipelines to deliver biologically meaningful insights on microbiome function. Here, we apply a standardized analytical pipeline to perform a comparative analysis of metatranscriptomic data from diverse microbial communities derived from mouse large intestine, cow rumen, kimchi culture, deep-sea thermal vent and permafrost. Sequence similarity searches allowed annotation of 19 to 76% of putative messenger RNA (mRNA) reads, with the highest frequency in the kimchi dataset due to its relatively low complexity and availability of closely related reference genomes. Metatranscriptomic datasets exhibited distinct taxonomic and functional signatures. From a metabolic perspective, we identified a common core of enzymes involved in amino acid, energy and nucleotide metabolism and also identified microbiome-specific pathways such as phosphonate metabolism (deep sea) and glycan degradation pathways (cow rumen). Integrating taxonomic and functional annotations within a novel visualization framework revealed the contribution of different taxa to metabolic pathways, allowing the identification of taxa that contribute unique functions. The application of a single, standard pipeline confirms that the rich taxonomic and functional diversity observed across microbiomes is not simply an artefact of different analysis pipelines but instead reflects distinct environmental influences. At the same time, our findings show how microbiome complexity and availability of

  3. Aligning ontologies and integrating textual evidence for pathway analysis of microarray data

    Energy Technology Data Exchange (ETDEWEB)

    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.

  4. PIXE - a new method for elemental analysis

    International Nuclear Information System (INIS)

    Johansson, S.A.E.

    1983-01-01

    With elemental analysis we mean the determination of which chemical elements are present in a sample and of their concentration. This is an old and important problem in chemistry. The earliest methods were purely chemical and many such methods are still used. However, various methods based on physical principles have gradually become more and more important. One such method is neutron activation. When the sample is bombarded with neutrons it becomes radioactive and the various radioactive isotopes produced can be identified by the radiation they emit. From the measured intensity of the radiation one can calculate how much of a certain element that is present in the sample. Another possibility is to study the light emitted when the sample is excited in various ways. A spectroscopic investigation of the light can identify the chemical elements and allows also a determination of their concentration in the sample. In the same way, if a sample can be brought to emit X-rays, this radiation is also characteristic for the elements present and can be used to determine the elemental concentration. One such X-ray method which has been developed recently is PIXE. The name is an acronym for Particle Induced X-ray Emission and indicates the principle of the method. Particles in this context means heavy, charged particles such as protons and a-particles of rather high energy. Hence, in PIXE-analysis the sample is irradiated in the beam of an accelerator and the emitted X-rays are studied. (author)

  5. Integrated QSAR study for inhibitors of Hedgehog Signal Pathway against multiple cell lines:a collaborative filtering method.

    Science.gov (United States)

    Gao, Jun; Che, Dongsheng; Zheng, Vincent W; Zhu, Ruixin; Liu, Qi

    2012-07-31

    The Hedgehog Signaling Pathway is one of signaling pathways that are very important to embryonic development. The participation of inhibitors in the Hedgehog Signal Pathway can control cell growth and death, and searching novel inhibitors to the functioning of the pathway are in a great demand. As the matter of fact, effective inhibitors could provide efficient therapies for a wide range of malignancies, and targeting such pathway in cells represents a promising new paradigm for cell growth and death control. Current research mainly focuses on the syntheses of the inhibitors of cyclopamine derivatives, which bind specifically to the Smo protein, and can be used for cancer therapy. While quantitatively structure-activity relationship (QSAR) studies have been performed for these compounds among different cell lines, none of them have achieved acceptable results in the prediction of activity values of new compounds. In this study, we proposed a novel collaborative QSAR model for inhibitors of the Hedgehog Signaling Pathway by integration the information from multiple cell lines. Such a model is expected to substantially improve the QSAR ability from single cell lines, and provide useful clues in developing clinically effective inhibitors and modifications of parent lead compounds for target on the Hedgehog Signaling Pathway. In this study, we have presented: (1) a collaborative QSAR model, which is used to integrate information among multiple cell lines to boost the QSAR results, rather than only a single cell line QSAR modeling. Our experiments have shown that the performance of our model is significantly better than single cell line QSAR methods; and (2) an efficient feature selection strategy under such collaborative environment, which can derive the commonly important features related to the entire given cell lines, while simultaneously showing their specific contributions to a specific cell-line. Based on feature selection results, we have proposed several

  6. Point Analysis in Java applied to histological images of the perforant pathway: a user's account.

    Science.gov (United States)

    Scorcioni, Ruggero; Wright, Susan N; Patrick Card, J; Ascoli, Giorgio A; Barrionuevo, Germán

    2008-01-01

    The freeware Java tool Point Analysis in Java (PAJ), created to perform 3D point analysis, was tested in an independent laboratory setting. The input data consisted of images of the hippocampal perforant pathway from serial immunocytochemical localizations of the rat brain in multiple views at different resolutions. The low magnification set (x2 objective) comprised the entire perforant pathway, while the high magnification set (x100 objective) allowed the identification of individual fibers. A preliminary stereological study revealed a striking linear relationship between the fiber count at high magnification and the optical density at low magnification. PAJ enabled fast analysis for down-sampled data sets and a friendly interface with automated plot drawings. Noted strengths included the multi-platform support as well as the free availability of the source code, conducive to a broad user base and maximum flexibility for ad hoc requirements. PAJ has great potential to extend its usability by (a) improving its graphical user interface, (b) increasing its input size limit, (c) improving response time for large data sets, and (d) potentially being integrated with other Java graphical tools such as ImageJ.

  7. RAMM: a system of computer programs for radionuclide pathway analysis calculations

    International Nuclear Information System (INIS)

    Lyon, R.B.

    1976-09-01

    A generalized system of computer programs, designated RAMM (Radioactive Materials Management) system, has been developed to assist in the analysis of the movement of radionuclides through the environment to man. RAMM incorporates the GASP IV continuous/discrete simulation system. A nodal approach is used whereby the system to be analyzed is split up into parts small enough that the distribution of nuclides within the node may be taken to be homogeneous. Pathways are defined between nodes, and appropriate transfer coefficients are input or generated. Output includes the time dependent contents of the nodes and dose rates, integrated doses and dose commitments of selected nodes. (author)

  8. Dependability Analysis Methods For Configurable Software

    International Nuclear Information System (INIS)

    Dahll, Gustav; Pulkkinen, Urho

    1996-01-01

    Configurable software systems are systems which are built up by standard software components in the same way as a hardware system is built up by standard hardware components. Such systems are often used in the control of NPPs, also in safety related applications. A reliability analysis of such systems is therefore necessary. This report discusses what configurable software is, and what is particular with respect to reliability assessment of such software. Two very commonly used techniques in traditional reliability analysis, viz. failure mode, effect and criticality analysis (FMECA) and fault tree analysis are investigated. A real example is used to illustrate the discussed methods. Various aspects relevant to the assessment of the software reliability in such systems are discussed. Finally some models for quantitative software reliability assessment applicable on configurable software systems are described. (author)

  9. Organization of ascending auditory pathways in the pigeon (Columba livia) as determined by autoradiographic methods

    International Nuclear Information System (INIS)

    Correia, M.J.; Eden, A.R.; Westlund, K.N.; Coulter, J.D.

    1982-01-01

    A mixture of tritiated proline and fucose was injected into the labyrinthine endolymphatic space of 5 white king pigeons (Columba livia). Using standard autoradiographic techniques, the authors observed transsynaptic labeling in ascending auditory pathways to the level of the mesencephalon. Auditory system structures, ipsilateral to the injection site, which labeled heavily were the cochlear nerve, the magnocellular and angular nuclei, and the superior olive. Those ipsilateral structures which were slightly labeled were the lateral lemniscus and the dorsal part of the lateral mesencephalic nucleus. Contralateral structures which labeled were the superior olive, lateral lemniscus, and dorsal part of the lateral mesencephalic nucleus. The results of this study suggest that ascending auditory pathways (to the level of mesencephalon) in the pigeon are more similar to those described for mammals in general than previously thought. (Auth.)

  10. Organization of ascending auditory pathways in the pigeon (Columba livia) as determined by autoradiographic methods

    Energy Technology Data Exchange (ETDEWEB)

    Correia, M.J.; Eden, A.R.; Westlund, K.N.; Coulter, J.D. (Texas Univ., Galveston (USA). Medical Branch)

    1982-02-25

    A mixture of tritiated proline and fucose was injected into the labyrinthine endolymphatic space of 5 white king pigeons (Columba livia). Using standard autoradiographic techniques, the authors observed transsynaptic labeling in ascending auditory pathways to the level of the mesencephalon. Auditory system structures, ipsilateral to the injection site, which labeled heavily were the cochlear nerve, the magnocellular and angular nuclei, and the superior olive. Those ipsilateral structures which were slightly labeled were the lateral lemniscus and the dorsal part of the lateral mesencephalic nucleus. Contralateral structures which labeled were the superior olive, lateral lemniscus, and dorsal part of the lateral mesencephalic nucleus. The results of this study suggest that ascending auditory pathways (to the level of mesencephalon) in the pigeon are more similar to those described for mammals in general than previously thought.

  11. Monetary valuation with impact pathway analysis: Benefits of reducing nitrate leaching in European Catchments

    DEFF Research Database (Denmark)

    Andersen, Mikael Skou; Hansen, Morten Søes; Carstensen, Jacob

    2011-01-01

    Integrated assessment frameworks which can account comprehensively for the benefits related to water quality improvements have not yet been established. The main challenge is to link economic valuation with hydrological data in an appropriate way.We here explore the so-called ‘impact pathway...... approach’ as a novel analytical method in the area ofwater management. It can identify site- and catchment-specific benefits associated with management measures by linking economic and hydrological data through consecutive modelling stages, allowing for monetization of specific end point effects...

  12. Analysis of photosynthate translocation velocity and measurement of weighted average velocity in transporting pathway of crops

    International Nuclear Information System (INIS)

    Ge Cailin; Luo Shishi; Gong Jian; Zhang Hao; Ma Fei

    1996-08-01

    The translocation profile pattern of 14 C-photosynthate along the transporting pathway in crops were monitored by pulse-labelling a mature leaf with 14 CO 2 . The progressive spreading of translocation profile pattern along the sheath or stem indicates that the translocation of photosynthate along the sheath or stem proceed with a range of velocities rather than with just a single velocity. The method for measuring the weighted average velocity of photosynthate translocation along the sheath or stem was established in living crops. The weighted average velocity and the maximum velocity of photosynthate translocation along the sheath in rice and maize were measured actually. (4 figs., 3 tabs.)

  13. Pathway confirmation and flux analysis of central metabolic pathways in Desulfovibrio vulgaris Hildenborough using gas chromatography-mass spectrometry and fourier transform-ion cyclotron resonance mass spectrometry

    International Nuclear Information System (INIS)

    Tang, Yinjie; Pingitore, Francesco; Mukhopadhyay, Aindrila; Phan, Richard; Hazen, Terry C.; Keasling, Jay D.

    2006-01-01

    It has been proposed that during growth under anaerobic or oxygen-limited conditions Shewanella oneidensis MR-1 uses the serine-isocitrate lyase pathway common to many methylotrophic anaerobes, in which formaldehyde produced from pyruvate is condensed with glycine to form serine. The serine is then transformed through hydroxypyruvate and glycerate to enter central metabolism at phosphoglycerate. To examine its use of the serine-isocitrate lyase pathway under anaerobic conditions, we grew S. oneidensis MR-1 on [1-13C] lactate as the sole carbon source with either trimethylamine N-oxide (TMAO) or fumarate as an electron acceptor. Analysis of cellular metabolites indicates that a large percentage (>75 percent) of lactate was partially oxidized to either acetate or pyruvate. The 13C isotope distributions in amino acids and other key metabolites indicate that, under anaerobic conditions, a complete serine pathway is not present, and lactate is oxidized via a highly reversible serine degradation pathway. The labeling data also suggest significant activity in the anaplerotic (malic enzyme and phosphoenolpyruvatecarboxylase) and glyoxylate shunt (isocitrate lyase and malate synthase) reactions. Although the tricarboxylic acid (TCA) cycle is often observed to be incomplete in many other anaerobes (absence of 2-oxoglutaratede hydrogenase activity), isotopic labeling supports the existence of a complete TCA cycle in S. oneidensis MR-1 under TMAO reduction condition

  14. A single-run liquid chromatography mass spectrometry method to quantify neuroactive kynurenine pathway metabolites in rat plasma.

    Science.gov (United States)

    Orsatti, Laura; Speziale, Roberto; Orsale, Maria Vittoria; Caretti, Fulvia; Veneziano, Maria; Zini, Matteo; Monteagudo, Edith; Lyons, Kathryn; Beconi, Maria; Chan, Kelvin; Herbst, Todd; Toledo-Sherman, Leticia; Munoz-Sanjuan, Ignacio; Bonelli, Fabio; Dominguez, Celia

    2015-03-25

    Neuroactive metabolites in the kynurenine pathway of tryptophan catabolism are associated with neurodegenerative disorders. Tryptophan is transported across the blood-brain barrier and converted via the kynurenine pathway to N-formyl-L-kynurenine, which is further degraded to L-kynurenine. This metabolite can then generate a group of metabolites called kynurenines, most of which have neuroactive properties. The association of tryptophan catabolic pathway alterations with various central nervous system (CNS) pathologies has raised interest in analytical methods to accurately quantify kynurenines in body fluids. We here describe a rapid and sensitive reverse-phase HPLC-MS/MS method to quantify L-kynurenine (KYN), kynurenic acid (KYNA), 3-hydroxy-L-kynurenine (3HK) and anthranilic acid (AA) in rat plasma. Our goal was to quantify these metabolites in a single run; given their different physico-chemical properties, major efforts were devoted to develop a chromatography suitable for all metabolites that involves plasma protein precipitation with acetonitrile followed by chromatographic separation by C18 RP chromatography, detected by electrospray mass spectrometry. Quantitation range was 0.098-100 ng/ml for 3HK, 9.8-20,000 ng/ml for KYN, 0.49-1000 ng/ml for KYNA and AA. The method was linear (r>0.9963) and validation parameters were within acceptance range (calibration standards and QC accuracy within ±30%). Copyright © 2015 Elsevier B.V. All rights reserved.

  15. Cask crush pad analysis using detailed and simplified analysis methods

    International Nuclear Information System (INIS)

    Uldrich, E.D.; Hawkes, B.D.

    1997-01-01

    A crush pad has been designed and analyzed to absorb the kinetic energy of a hypothetically dropped spent nuclear fuel shipping cask into a 44-ft. deep cask unloading pool at the Fluorinel and Storage Facility (FAST). This facility, located at the Idaho Chemical Processing Plant (ICPP) at the Idaho national Engineering and Environmental Laboratory (INEEL), is a US Department of Energy site. The basis for this study is an analysis by Uldrich and Hawkes. The purpose of this analysis was to evaluate various hypothetical cask drop orientations to ensure that the crush pad design was adequate and the cask deceleration at impact was less than 100 g. It is demonstrated herein that a large spent fuel shipping cask, when dropped onto a foam crush pad, can be analyzed by either hand methods or by sophisticated dynamic finite element analysis using computer codes such as ABAQUS. Results from the two methods are compared to evaluate accuracy of the simplified hand analysis approach

  16. Advanced Analysis Methods in High Energy Physics

    Energy Technology Data Exchange (ETDEWEB)

    Pushpalatha C. Bhat

    2001-10-03

    During the coming decade, high energy physics experiments at the Fermilab Tevatron and around the globe will use very sophisticated equipment to record unprecedented amounts of data in the hope of making major discoveries that may unravel some of Nature's deepest mysteries. The discovery of the Higgs boson and signals of new physics may be around the corner. The use of advanced analysis techniques will be crucial in achieving these goals. The author discusses some of the novel methods of analysis that could prove to be particularly valuable for finding evidence of any new physics, for improving precision measurements and for exploring parameter spaces of theoretical models.

  17. Single-cell analysis reveals a link between CD3- and CD59-mediated signaling pathways in Jurkat T cells

    International Nuclear Information System (INIS)

    Lipp, A. M.

    2012-01-01

    Elevation of intracellular free calcium concentration ([Ca2+]i) is a key signal during T cell activation and is commonly used as a read-out parameter for stimulation of T cell signaling. Upon T cell stimulation a variety of calcium signals is produced by individual cells of the T cell population and the type of calcium signal strongly influences cell fate decisions. The heterogeneous nature of T cells is masked in ensemble measurements, which highlights the need for single-cell measurements. In this study we used single-cell calcium measurements in Jurkat cells to investigate signaling pathways, which are triggered by different proteins, namely CD3 and CD59. By application of an automated cluster algorithm the presented assay provides unbiased analysis of a large data set of individual calcium time traces generated by the whole cell population. By using this method we could demonstrate that the Jurkat population generates heterogeneous calcium signals in a stimulus-dependent manner. Furthermore, our data revealed the existence of a link between CD3- and CD59-mediated signaling pathways. Single-cell calcium measurements in Jurkat cells expressing different levels of the T cell receptor (TCR) complex indicated that CD59-mediated calcium signaling is critically dependent on TCR surface expression levels. In addition, triggering CD59-mediated calcium signaling resulted in down-regulation of TCR surface expression levels, which is known to happen upon direct TCR triggering too. Moreover, by using siRNA-mediated protein knock-downs and protein knock-out Jurkat mutants we could show that CD3- and CD59-mediated calcium signaling require identical key proteins. We therefore explored by which mechanism CD59-mediated signaling couples into TCR-mediated signaling. Fluorescence recovery after photobleaching (FRAP) experiments and live-cell protein-protein interaction assays provided no evidence of a direct physical interaction between CD3- and CD59-mediated signaling pathways

  18. Spatial Analysis Methods of Road Traffic Collisions

    DEFF Research Database (Denmark)

    Loo, Becky P. Y.; Anderson, Tessa Kate

    Spatial Analysis Methods of Road Traffic Collisions centers on the geographical nature of road crashes, and uses spatial methods to provide a greater understanding of the patterns and processes that cause them. Written by internationally known experts in the field of transport geography, the book...... outlines the key issues in identifying hazardous road locations (HRLs), considers current approaches used for reducing and preventing road traffic collisions, and outlines a strategy for improved road safety. The book covers spatial accuracy, validation, and other statistical issues, as well as link...

  19. Simple gas chromatographic method for furfural analysis.

    Science.gov (United States)

    Gaspar, Elvira M S M; Lopes, João F

    2009-04-03

    A new, simple, gas chromatographic method was developed for the direct analysis of 5-hydroxymethylfurfural (5-HMF), 2-furfural (2-F) and 5-methylfurfural (5-MF) in liquid and water soluble foods, using direct immersion SPME coupled to GC-FID and/or GC-TOF-MS. The fiber (DVB/CAR/PDMS) conditions were optimized: pH effect, temperature, adsorption and desorption times. The method is simple and accurate (RSDfurfurals will contribute to characterise and quantify their presence in the human diet.

  20. Transcriptome analysis of bitter acid biosynthesis and precursor pathways in hop (Humulus lupulus

    Directory of Open Access Journals (Sweden)

    Clark Shawn M

    2013-01-01

    Full Text Available Abstract 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

  1. Tomographic phase analysis to detect the site of accessory conduction pathway in Wolff-Parkinson-White syndrome

    International Nuclear Information System (INIS)

    Nakajima, K.; Bunko, H.; Tada, A.; Tonami, N.; Taki, J.; Nanbu, I.; Hisada, K.; Misaki, T.; Iwa, T.

    1984-01-01

    Phase analysis has been applied to Wolff-Parkinson-White syndrome (WPW) to detect the site of accessory conduction pathway (ACP); however, there was a limitation to estimate the precise location of ACP by planar phase analysis. In this study, the authors applied phase analysis to gated blood pool tomography. Twelve patients with WPW who underwent epicardial mapping and surgical division of ACP were studied by both of gated emission computed tomography (GECT) and routine gated blood pool study (GBPS). The GBPS was performed with Tc-99m red blood cells in multiple projections; modified left anterior oblique, right anterior oblique and/or left lateral views. In GECT, short axial, horizontal and vertical long axial blood pool images were reconstructed. Phase analysis was performed using fundamental frequency of the Fourier transform in both GECT and GBPS images, and abnormal initial contractions on both the planar and tomographic phase analysis were compared with the location of surgically confirmed ACPs. In planar phase analysis, abnormal initial phase was identified in 7 out of 12 (58%) patients, while in tomographic phase analysis, the localization of ACP was predicted in 11 out of 12 (92%) patients. Tomographic phase analysis is superior to planar phase images in 8 out of 12 patients to estimate the location of ACP. Phase analysis by GECT can avoid overlap of blood pool in cardiac chambers and has advantage to identify the propagation of phase three-dimensionally. Tomographic phase analysis is a good adjunctive method for patients with WPW to estimate the site of ACP

  2. Tomographic phase analysis to detect the site of accessory conduction pathway in Wolff-Parkinson-White syndrome

    Energy Technology Data Exchange (ETDEWEB)

    Nakajima, K.; Bunko, H.; Tada, A.; Tonami, N.; Taki, J.; Nanbu, I.; Hisada, K.; Misaki, T.; Iwa, T.

    1984-01-01

    Phase analysis has been applied to Wolff-Parkinson-White syndrome (WPW) to detect the site of accessory conduction pathway (ACP); however, there was a limitation to estimate the precise location of ACP by planar phase analysis. In this study, the authors applied phase analysis to gated blood pool tomography. Twelve patients with WPW who underwent epicardial mapping and surgical division of ACP were studied by both of gated emission computed tomography (GECT) and routine gated blood pool study (GBPS). The GBPS was performed with Tc-99m red blood cells in multiple projections; modified left anterior oblique, right anterior oblique and/or left lateral views. In GECT, short axial, horizontal and vertical long axial blood pool images were reconstructed. Phase analysis was performed using fundamental frequency of the Fourier transform in both GECT and GBPS images, and abnormal initial contractions on both the planar and tomographic phase analysis were compared with the location of surgically confirmed ACPs. In planar phase analysis, abnormal initial phase was identified in 7 out of 12 (58%) patients, while in tomographic phase analysis, the localization of ACP was predicted in 11 out of 12 (92%) patients. Tomographic phase analysis is superior to planar phase images in 8 out of 12 patients to estimate the location of ACP. Phase analysis by GECT can avoid overlap of blood pool in cardiac chambers and has advantage to identify the propagation of phase three-dimensionally. Tomographic phase analysis is a good adjunctive method for patients with WPW to estimate the site of ACP.

  3. Identification and pathway analysis of microRNAs with no previous involvement in breast cancer.

    Directory of Open Access Journals (Sweden)

    Sandra Romero-Cordoba

    Full Text Available 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.

  4. Multi-criteria decision analysis of energy system transformation pathways: A case study for Switzerland

    International Nuclear Information System (INIS)

    Volkart, Kathrin; Weidmann, Nicolas; Bauer, Christian; Hirschberg, Stefan

    2017-01-01

    Two recent political decisions are expected to frame the development of the Swiss energy system in the coming decades: the nuclear phase-out and the greenhouse gas (GHG) emission reduction target. To accomplish both of them, low-carbon technologies based on renewable energy and Carbon Capture and Storage (CCS) are expected to gain importance. The objective of the present work is to support prospective Swiss energy policy-making by providing a detailed sustainability analysis of possible energy system transformation pathways. For this purpose, the results of the scenario quantification with an energy system model are coupled with multi-criteria sustainability analysis. Two climate protection and one reference scenario are addressed, and the trade-offs between the scenarios are analysed based on a set of 12 interdisciplinary indicators. Implementing a stringent climate policy in Switzerland is associated with co-benefits such as less fossil resource use, less fatalities in severe accidents in the energy sector, less societal conflicts and higher resource autonomy. The availability and implementation of CCS allows for achieving the GHG emission reduction target at lower costs, but at the expense of a more fossil fuel-based energy system. - Highlights: • Three energy system transformation pathways for Switzerland are analysed. • A set of policy-relevant sustainability indicators are quantified for each pathway. • Implementing a stringent climate policy in Switzerland is associated with co-benefits. • In the CCS scenario fossil fuel use increases, but the total system costs are lower. • Fossil-fuelled transport substantially contributes to most of the addressed criteria.

  5. Neutron activation analysis: principle and methods

    International Nuclear Information System (INIS)

    Reddy, A.V.R.; Acharya, R.

    2006-01-01

    Neutron activation analysis (NAA) is a powerful isotope specific nuclear analytical technique for simultaneous determination of elemental composition of major, minor and trace elements in diverse matrices. The technique is capable of yielding high analytical sensitivity and low detection limits (ppm to ppb). Due to high penetration power of neutrons and gamma rays, NAA experiences negligible matrix effects in the samples of different origins. Depending on the sample matrix and element of interest NAA technique is used non-destructively, known as instrumental neutron activation analysis (INAA), or through chemical NAA methods. The present article describes principle of NAA, different methods and gives a overview some applications in the fields like environment, biology, geology, material sciences, nuclear technology and forensic sciences. (author)

  6. Digital dream analysis: a revised method.

    Science.gov (United States)

    Bulkeley, Kelly

    2014-10-01

    This article demonstrates the use of a digital word search method designed to provide greater accuracy, objectivity, and speed in the study of dreams. A revised template of 40 word search categories, built into the website of the Sleep and Dream Database (SDDb), is applied to four "classic" sets of dreams: The male and female "Norm" dreams of Hall and Van de Castle (1966), the "Engine Man" dreams discussed by Hobson (1988), and the "Barb Sanders Baseline 250" dreams examined by Domhoff (2003). A word search analysis of these original dream reports shows that a digital approach can accurately identify many of the same distinctive patterns of content found by previous investigators using much more laborious and time-consuming methods. The results of this study emphasize the compatibility of word search technologies with traditional approaches to dream content analysis. Copyright © 2014 Elsevier Inc. All rights reserved.

  7. Numerical methods and analysis of multiscale problems

    CERN Document Server

    Madureira, Alexandre L

    2017-01-01

    This book is about numerical modeling of multiscale problems, and introduces several asymptotic analysis and numerical techniques which are necessary for a proper approximation of equations that depend on different physical scales. Aimed at advanced undergraduate and graduate students in mathematics, engineering and physics – or researchers seeking a no-nonsense approach –, it discusses examples in their simplest possible settings, removing mathematical hurdles that might hinder a clear understanding of the methods. The problems considered are given by singular perturbed reaction advection diffusion equations in one and two-dimensional domains, partial differential equations in domains with rough boundaries, and equations with oscillatory coefficients. This work shows how asymptotic analysis can be used to develop and analyze models and numerical methods that are robust and work well for a wide range of parameters.

  8. Qualitative data analysis a methods sourcebook

    CERN Document Server

    Miles, Matthew B; Saldana, Johnny

    2014-01-01

    The Third Edition of Miles & Huberman's classic research methods text is updated and streamlined by Johnny SaldaNa, author of The Coding Manual for Qualitative Researchers. Several of the data display strategies from previous editions are now presented in re-envisioned and reorganized formats to enhance reader accessibility and comprehension. The Third Edition's presentation of the fundamentals of research design and data management is followed by five distinct methods of analysis: exploring, describing, ordering, explaining, and predicting. Miles and Huberman's original research studies are profiled and accompanied with new examples from SaldaNa's recent qualitative work. The book's most celebrated chapter, "Drawing and Verifying Conclusions," is retained and revised, and the chapter on report writing has been greatly expanded, and is now called "Writing About Qualitative Research." Comprehensive and authoritative, Qualitative Data Analysis has been elegantly revised for a new generation of qualitative r...

  9. An exergy method for compressor performance analysis

    Energy Technology Data Exchange (ETDEWEB)

    McGovern, J A; Harte, S [Trinity Coll., Dublin (Ireland)

    1995-07-01

    An exergy method for compressor performance analysis is presented. The purpose of this is to identify and quantify defects in the use of a compressor`s shaft power. This information can be used as the basis for compressor design improvements. The defects are attributed to friction, irreversible heat transfer, fluid throttling, and irreversible fluid mixing. They are described, on a common basis, as exergy destruction rates and their locations are identified. The method can be used with any type of positive displacement compressor. It is most readily applied where a detailed computer simulation program is available for the compressor. An analysis of an open reciprocating refrigeration compressor that used R12 refrigerant is given as an example. The results that are presented consist of graphs of the instantaneous rates of exergy destruction according to the mechanisms involved, a pie chart of the breakdown of the average shaft power wastage by mechanism, and a pie chart with a breakdown by location. (author)

  10. Methods for genetic linkage analysis using trisomies.

    OpenAIRE

    Feingold, E; Lamb, N E; Sherman, S L

    1995-01-01

    Certain genetic disorders are rare in the general population, but more common in individuals with specific trisomies. Examples of this include leukemia and duodenal atresia in trisomy 21. This paper presents a linkage analysis method for using trisomic individuals to map genes for such traits. It is based on a very general gene-specific dosage model that posits that the trait is caused by specific effects of different alleles at one or a few loci and that duplicate copies of "susceptibility" ...

  11. Machine Learning Methods for Production Cases Analysis

    Science.gov (United States)

    Mokrova, Nataliya V.; Mokrov, Alexander M.; Safonova, Alexandra V.; Vishnyakov, Igor V.

    2018-03-01

    Approach to analysis of events occurring during the production process were proposed. Described machine learning system is able to solve classification tasks related to production control and hazard identification at an early stage. Descriptors of the internal production network data were used for training and testing of applied models. k-Nearest Neighbors and Random forest methods were used to illustrate and analyze proposed solution. The quality of the developed classifiers was estimated using standard statistical metrics, such as precision, recall and accuracy.

  12. Safety relief valve alternate analysis method

    International Nuclear Information System (INIS)

    Adams, R.H.; Javid, A.; Khatua, T.P.

    1981-01-01

    An experimental test program was started in the United States in 1976 to define and quantify Safety Relief Valve (SRV) phenomena in General Electric Mark I Suppression Chambers. The testing considered several discharged devices and was used to correlate SRV load prediction models. The program was funded by utilities with Mark I containments and has resulted in a detailed SRV load definition as a portion of the Mark I containment program Load Definition Report (LDR). The (USNRC) has reviewed and approved the LDR SRV load definition. In addition, the USNRC has permitted calibration of structural models used for predicting torus response to SRV loads. Model calibration is subject to confirmatory in-plant testing. The SRV methodology given in the LDR requires that transient dynamic pressures be applied to a torus structural model that includes a fluid added mass matrix. Preliminary evaluations of torus response have indicated order of magnitude conservatisms, with respect to test results, which could result in unrealistic containment modifications. In addition, structural response trends observed in full-scale tests between cold pipe, first valve actuation and hot pipe, subsequent valve actuation conditions have not been duplicated using current analysis methods. It was suggested by others that an energy approach using current fluid models be utilized to define loads. An alternate SRV analysis method is defined to correct suppression chamber structural response to a level that permits economical but conservative design. Simple analogs are developed for the purpose of correcting the analytical response obtained from LDR analysis methods. Analogs evaluated considered forced vibration and free vibration structural response. The corrected response correlated well with in-plant test response. The correlation of the analytical model at test conditions permits application of the alternate analysis method at design conditions. (orig./HP)

  13. Analysis and comparison of biometric methods

    OpenAIRE

    Zatloukal, Filip

    2011-01-01

    The thesis deals with biometrics and biometric systems and the possibility to use these systems in the enterprise. Aim of this study is an analysis and description of selected types of biometric identification methods and their advantages and shortcomings. The work is divided into two parts. The first part is theoretical, describes the basic concepts of biometrics, biometric identification criteria, currently used identification systems, the ways of biometric systems use, performance measurem...

  14. Automated tool for virtual screening and pharmacology-based pathway prediction and analysis

    Directory of Open Access Journals (Sweden)

    Sugandh Kumar

    2017-10-01

    Full Text Available The virtual screening is an effective tool for the lead identification in drug discovery. However, there are limited numbers of crystal structures available as compared to the number of biological sequences which makes (Structure Based Drug Discovery SBDD a difficult choice. The current tool is an attempt to automate the protein structure modelling and automatic virtual screening followed by pharmacology-based prediction and analysis. Starting from sequence(s, this tool automates protein structure modelling, binding site identification, automated docking, ligand preparation, post docking analysis and identification of hits in the biological pathways that can be modulated by a group of ligands. This automation helps in the characterization of ligands selectivity and action of ligands on a complex biological molecular network as well as on individual receptor. The judicial combination of the ligands binding different receptors can be used to inhibit selective biological pathways in a disease. This tool also allows the user to systemically investigate network-dependent effects of a drug or drug candidate.

  15. Perturbations in amino acids and metabolic pathways in osteoarthritis patients determined by targeted metabolomics analysis.

    Science.gov (United States)

    Chen, Rui; Han, Su; Liu, Xuefeng; Wang, Kunpeng; Zhou, Yong; Yang, Chundong; Zhang, Xi

    2018-05-15

    Osteoarthritis (OA) is a degenerative synovial joint disease affecting people worldwide. However, the exact pathogenesis of OA remains unclear. Metabolomics analysis was performed to obtain insight into possible pathogenic mechanisms and diagnostic biomarkers of OA. Ultra-high performance liquid chromatography-triple quadrupole mass spectrometry (UPLC-TQ-MS), followed by multivariate statistical analysis, was used to determine the serum amino acid profiles of 32 OA patients and 35 healthy controls. Variable importance for project values and Student's t-test were used to determine the metabolic abnormalities in OA. Another 30 OA patients were used as independent samples to validate the alterations in amino acids. MetaboAnalyst was used to identify the key amino acid pathways and construct metabolic networks describing their relationships. A total of 25 amino acids and four biogenic amines were detected by UPLC-TQ-MS. Differences in amino acid profiles were found between the healthy controls and OA patients. Alanine, γ-aminobutyric acid and 4-hydroxy-l-proline were important biomarkers distinguishing OA patients from healthy controls. The metabolic pathways with the most significant effects were involved in metabolism of alanine, aspartate, glutamate, arginine and proline. The results of this study improve understanding of the amino acid metabolic abnormalities and pathogenic mechanisms of OA at the molecular level. The metabolic perturbations may be important for the diagnosis and prevention of OA. Copyright © 2018 Elsevier B.V. All rights reserved.

  16. A meta-analysis of biomarkers related to oxidative stress and nitric oxide pathway in migraine.

    Science.gov (United States)

    Neri, Monica; Frustaci, Alessandra; Milic, Mirta; Valdiglesias, Vanessa; Fini, Massimo; Bonassi, Stefano; Barbanti, Piero

    2015-09-01

    Oxidative and nitrosative stress are considered key events in the still unclear pathophysiology of migraine. Studies comparing the level of biomarkers related to nitric oxide (NO) pathway/oxidative stress in the blood/urine of migraineurs vs. unaffected controls were extracted from the PubMed database. Summary estimates of mean ratios (MR) were carried out whenever a minimum of three papers were available. Nineteen studies were included in the meta-analyses, accounting for more than 1000 patients and controls, and compared with existing literature. Most studies measuring superoxide dismutase (SOD) showed lower activity in cases, although the meta-analysis in erythrocytes gave null results. On the contrary, plasma levels of thiobarbituric acid reactive substances (TBARS), an aspecific biomarker of oxidative damage, showed a meta-MR of 2.20 (95% CI: 1.65-2.93). As for NOs, no significant results were found in plasma, serum and urine. However, higher levels were shown during attacks, in patients with aura, and an effect of diet was found. The analysis of glutathione precursor homocysteine and asymmetric dimethylarginine (ADMA), an NO synthase inhibitor, gave inconclusive results. The role of the oxidative pathway in migraine is still uncertain. Interesting evidence emerged for TBARS and SOD, and concerning the possible role of diet in the control of NOx levels. © International Headache Society 2015.

  17. Statistical trend analysis methods for temporal phenomena

    International Nuclear Information System (INIS)

    Lehtinen, E.; Pulkkinen, U.; Poern, K.

    1997-04-01

    We consider point events occurring in a random way in time. In many applications the pattern of occurrence is of intrinsic interest as indicating a trend or some other systematic feature in the rate of occurrence. The purpose of this report is to survey briefly different statistical trend analysis methods and illustrate their applicability to temporal phenomena in particular. The trend testing of point events is usually seen as the testing of the hypotheses concerning the intensity of the occurrence of events. When the intensity function is parametrized, the testing of trend is a typical parametric testing problem. In industrial applications the operational experience generally does not suggest any specified model and method in advance. Therefore, and particularly, if the Poisson process assumption is very questionable, it is desirable to apply tests that are valid for a wide variety of possible processes. The alternative approach for trend testing is to use some non-parametric procedure. In this report we have presented four non-parametric tests: The Cox-Stuart test, the Wilcoxon signed ranks test, the Mann test, and the exponential ordered scores test. In addition to the classical parametric and non-parametric approaches we have also considered the Bayesian trend analysis. First we discuss a Bayesian model, which is based on a power law intensity model. The Bayesian statistical inferences are based on the analysis of the posterior distribution of the trend parameters, and the probability of trend is immediately seen from these distributions. We applied some of the methods discussed in an example case. It should be noted, that this report is a feasibility study rather than a scientific evaluation of statistical methods, and the examples can only be seen as demonstrations of the methods

  18. Statistical trend analysis methods for temporal phenomena

    Energy Technology Data Exchange (ETDEWEB)

    Lehtinen, E.; Pulkkinen, U. [VTT Automation, (Finland); Poern, K. [Poern Consulting, Nykoeping (Sweden)

    1997-04-01

    We consider point events occurring in a random way in time. In many applications the pattern of occurrence is of intrinsic interest as indicating a trend or some other systematic feature in the rate of occurrence. The purpose of this report is to survey briefly different statistical trend analysis methods and illustrate their applicability to temporal phenomena in particular. The trend testing of point events is usually seen as the testing of the hypotheses concerning the intensity of the occurrence of events. When the intensity function is parametrized, the testing of trend is a typical parametric testing problem. In industrial applications the operational experience generally does not suggest any specified model and method in advance. Therefore, and particularly, if the Poisson process assumption is very questionable, it is desirable to apply tests that are valid for a wide variety of possible processes. The alternative approach for trend testing is to use some non-parametric procedure. In this report we have presented four non-parametric tests: The Cox-Stuart test, the Wilcoxon signed ranks test, the Mann test, and the exponential ordered scores test. In addition to the classical parametric and non-parametric approaches we have also considered the Bayesian trend analysis. First we discuss a Bayesian model, which is based on a power law intensity model. The Bayesian statistical inferences are based on the analysis of the posterior distribution of the trend parameters, and the probability of trend is immediately seen from these distributions. We applied some of the methods discussed in an example case. It should be noted, that this report is a feasibility study rather than a scientific evaluation of statistical methods, and the examples can only be seen as demonstrations of the methods. 14 refs, 10 figs.

  19. Analysis Method for Integrating Components of Product

    Energy Technology Data Exchange (ETDEWEB)

    Choi, Jun Ho [Inzest Co. Ltd, Seoul (Korea, Republic of); Lee, Kun Sang [Kookmin Univ., Seoul (Korea, Republic of)

    2017-04-15

    This paper presents some of the methods used to incorporate the parts constituting a product. A new relation function concept and its structure are introduced to analyze the relationships of component parts. This relation function has three types of information, which can be used to establish a relation function structure. The relation function structure of the analysis criteria was established to analyze and present the data. The priority components determined by the analysis criteria can be integrated. The analysis criteria were divided based on their number and orientation, as well as their direct or indirect characteristic feature. This paper presents a design algorithm for component integration. This algorithm was applied to actual products, and the components inside the product were integrated. Therefore, the proposed algorithm was used to conduct research to improve the brake discs for bicycles. As a result, an improved product similar to the related function structure was actually created.

  20. Analysis Method for Integrating Components of Product

    International Nuclear Information System (INIS)

    Choi, Jun Ho; Lee, Kun Sang

    2017-01-01

    This paper presents some of the methods used to incorporate the parts constituting a product. A new relation function concept and its structure are introduced to analyze the relationships of component parts. This relation function has three types of information, which can be used to establish a relation function structure. The relation function structure of the analysis criteria was established to analyze and present the data. The priority components determined by the analysis criteria can be integrated. The analysis criteria were divided based on their number and orientation, as well as their direct or indirect characteristic feature. This paper presents a design algorithm for component integration. This algorithm was applied to actual products, and the components inside the product were integrated. Therefore, the proposed algorithm was used to conduct research to improve the brake discs for bicycles. As a result, an improved product similar to the related function structure was actually created.

  1. Probabilistic methods in fire-risk analysis

    International Nuclear Information System (INIS)

    Brandyberry, M.D.

    1989-01-01

    The first part of this work outlines a method for assessing the frequency of ignition of a consumer product in a building and shows how the method would be used in an example scenario utilizing upholstered furniture as the product and radiant auxiliary heating devices (electric heaters, wood stoves) as the ignition source. Deterministic thermal models of the heat-transport processes are coupled with parameter uncertainty analysis of the models and with a probabilistic analysis of the events involved in a typical scenario. This leads to a distribution for the frequency of ignition for the product. In second part, fire-risk analysis as currently used in nuclear plants is outlines along with a discussion of the relevant uncertainties. The use of the computer code COMPBRN is discussed for use in the fire-growth analysis along with the use of response-surface methodology to quantify uncertainties in the code's use. Generalized response surfaces are developed for temperature versus time for a cable tray, as well as a surface for the hot gas layer temperature and depth for a room of arbitrary geometry within a typical nuclear power plant compartment. These surfaces are then used to simulate the cable tray damage time in a compartment fire experiment

  2. An unconventional method of quantitative microstructural analysis

    International Nuclear Information System (INIS)

    Rastani, M.

    1995-01-01

    The experiment described here introduces a simple methodology which could be used to replace the time-consuming and expensive conventional methods of metallographic and quantitative analysis of thermal treatment effect on microstructure. The method is ideal for the microstructural evaluation of tungsten filaments and other wire samples such as copper wire which can be conveniently coiled. Ten such samples were heat treated by ohmic resistance at temperatures which were expected to span the recrystallization range. After treatment, the samples were evaluated in the elastic recovery test. The normalized elastic recovery factor was defined in terms of these deflections. Experimentally it has shown that elastic recovery factor depends on the degree of recrystallization. In other words this factor is used to determine the fraction of unrecrystallized material. Because the elastic recovery method examines the whole filament rather than just one section through the filament as in metallographical method, it more accurately measures the degree of recrystallization. The method also takes a considerably shorter time and cost compared to the conventional method

  3. Homotopy analysis method for neutron diffusion calculations

    International Nuclear Information System (INIS)

    Cavdar, S.

    2009-01-01

    The Homotopy Analysis Method (HAM), proposed in 1992 by Shi Jun Liao and has been developed since then, is based on a fundamental concept in differential geometry and topology, the homotopy. It has proved useful for problems involving algebraic, linear/non-linear, ordinary/partial differential and differential-integral equations being an analytic, recursive method that provides a series sum solution. It has the advantage of offering a certain freedom for the choice of its arguments such as the initial guess, the auxiliary linear operator and the convergence control parameter, and it allows us to effectively control the rate and region of convergence of the series solution. HAM is applied for the fixed source neutron diffusion equation in this work, which is a part of our research motivated by the question of whether methods for solving the neutron diffusion equation that yield straightforward expressions but able to provide a solution of reasonable accuracy exist such that we could avoid analytic methods that are widely used but either fail to solve the problem or provide solutions through many intricate expressions that are likely to contain mistakes or numerical methods that require powerful computational resources and advanced programming skills due to their very nature or intricate mathematical fundamentals. Fourier basis are employed for expressing the initial guess due to the structure of the problem and its boundary conditions. We present the results in comparison with other widely used methods of Adomian Decomposition and Variable Separation.

  4. Detector Simulation: Data Treatment and Analysis Methods

    CERN Document Server

    Apostolakis, J

    2011-01-01

    Detector Simulation in 'Data Treatment and Analysis Methods', part of 'Landolt-Börnstein - Group I Elementary Particles, Nuclei and Atoms: Numerical Data and Functional Relationships in Science and Technology, Volume 21B1: Detectors for Particles and Radiation. Part 1: Principles and Methods'. This document is part of Part 1 'Principles and Methods' of Subvolume B 'Detectors for Particles and Radiation' of Volume 21 'Elementary Particles' of Landolt-Börnstein - Group I 'Elementary Particles, Nuclei and Atoms'. It contains the Section '4.1 Detector Simulation' of Chapter '4 Data Treatment and Analysis Methods' with the content: 4.1 Detector Simulation 4.1.1 Overview of simulation 4.1.1.1 Uses of detector simulation 4.1.2 Stages and types of simulation 4.1.2.1 Tools for event generation and detector simulation 4.1.2.2 Level of simulation and computation time 4.1.2.3 Radiation effects and background studies 4.1.3 Components of detector simulation 4.1.3.1 Geometry modeling 4.1.3.2 External fields 4.1.3.3 Intro...

  5. Data Analysis Methods for Library Marketing

    Science.gov (United States)

    Minami, Toshiro; Kim, Eunja

    Our society is rapidly changing to information society, where the needs and requests of the people on information access are different widely from person to person. Library's mission is to provide its users, or patrons, with the most appropriate information. Libraries have to know the profiles of their patrons, in order to achieve such a role. The aim of library marketing is to develop methods based on the library data, such as circulation records, book catalogs, book-usage data, and others. In this paper we discuss the methodology and imporatnce of library marketing at the beginning. Then we demonstrate its usefulness through some examples of analysis methods applied to the circulation records in Kyushu University and Guacheon Library, and some implication that obtained as the results of these methods. Our research is a big beginning towards the future when library marketing is an unavoidable tool.

  6. Phosphorus analysis in milk samples by neutron activation analysis method

    International Nuclear Information System (INIS)

    Oliveira, R.M. de; Cunha, I.I.L.

    1991-01-01

    The determination of phosphorus in milk samples by instrumental thermal neutron activation analysis is described. The procedure involves a short irradiation in a nuclear reactor and measurement of the beta radiation emitted by phosphorus - 32 after a suitable decay period. The sources of error were studied and the established method was applied to standard reference materials of known phosphorus content. (author)

  7. Pathway analysis for intracellular Porphyromonas gingivalis using a strain ATCC 33277 specific database

    Directory of Open Access Journals (Sweden)

    Wang Tiansong

    2009-09-01

    Full Text Available Abstract Background Porphyromonas gingivalis is a Gram-negative intracellular pathogen associated with periodontal disease. We have previously reported on whole-cell quantitative proteomic analyses to investigate the differential expression of virulence factors as the organism transitions from an extracellular to intracellular lifestyle. The original results with the invasive strain P. gingivalis ATCC 33277 were obtained using the genome sequence available at the time, strain W83 [GenBank: AE015924]. We present here a re-processed dataset using the recently published genome annotation specific for strain ATCC 33277 [GenBank: AP009380] and an analysis of differential abundance based on metabolic pathways rather than individual proteins. Results Qualitative detection was observed for 1266 proteins using the strain ATCC 33277 annotation for 18 hour internalized P. gingivalis within human gingival epithelial cells and controls exposed to gingival cell culture medium, an improvement of 7% over the W83 annotation. Internalized cells showed increased abundance of proteins in the energy pathway from asparagine/aspartate amino acids to ATP. The pathway producing one short chain fatty acid, propionate, showed increased abundance, while that of another, butyrate, trended towards decreased abundance. The translational machinery, including ribosomal proteins and tRNA synthetases, showed a significant increase in protein relative abundance, as did proteins responsible for transcription. Conclusion Use of the ATCC 33277 specific genome annotation resulted in improved proteome coverage with respect to the number of proteins observed both qualitatively in terms of protein identifications and quantitatively in terms of the number of calculated abundance ratios. Pathway analysis showed a significant increase in overall protein synthetic and transcriptional machinery in the absence of significant growth. These results suggest that the interior of host cells

  8. Integrating Multiple Microarray Data for Cancer Pathway Analysis Using Bootstrapping K-S Test

    Directory of Open Access Journals (Sweden)

    Bing Han

    2009-01-01

    Full Text Available Previous applications of microarray technology for cancer research have mostly focused on identifying genes that are differentially expressed between a particular cancer and normal cells. In a biological system, genes perform different molecular functions and regulate various biological processes via interactions with other genes thus forming a variety of complex networks. Therefore, it is critical to understand the relationship (e.g., interactions between genes across different types of cancer in order to gain insights into the molecular mechanisms of cancer. Here we propose an integrative method based on the bootstrapping Kolmogorov-Smirnov test and a large set of microarray data produced with various types of cancer to discover common molecular changes in cells from normal state to cancerous state. We evaluate our method using three key pathways related to cancer and demonstrate that it is capable of finding meaningful alterations in gene relations.

  9. Environmental, health, and safety decision making for naturally occurring radioactive materials in producing operations using pathway exposure analysis

    International Nuclear Information System (INIS)

    Miller, H.T.; Cook, L.M.

    1991-01-01

    A number of health and safety issues have arisen because of the occurrence of NORM, naturally occurring radioactive materials of the 226 radium and 228 radium decay chains, in production operations. Issues such as risk to workers or the general public, disposal of contaminated production fluids, disposal of NORM removed in cleaning equipment and tubing, and procedures to follow in well rework, equipment decontamination and other types of maintenance must be addressed. This paper describes the application of a procedural aid to decision making known as pathway exposure analysis to these issues. The procedure examines the radiation exposure of individuals and population groups by calculating the dose from each exposure route and pathway. The sum of these is used to calculate the overall risk to the individual or the group. This method can be used to examine management and procedural options to identify the option offering the smallest risk. Risk information coupled with cost estimates then permits management maximum utilization of its available resources

  10. Benchmarking pathway interaction network for colorectal cancer to identify dysregulated pathways

    Directory of Open Access Journals (Sweden)

    Q. Wang

    Full Text Available Different pathways act synergistically to participate in many biological processes. Thus, the purpose of our study was to extract dysregulated pathways to investigate the pathogenesis of colorectal cancer (CRC based on the functional dependency among pathways. Protein-protein interaction (PPI information and pathway data were retrieved from STRING and Reactome databases, respectively. After genes were aligned to the pathways, each pathway activity was calculated using the principal component analysis (PCA method, and the seed pathway was discovered. Subsequently, we constructed the pathway interaction network (PIN, where each node represented a biological pathway based on gene expression profile, PPI data, as well as pathways. Dysregulated pathways were then selected from the PIN according to classification performance and seed pathway. A PIN including 11,960 interactions was constructed to identify dysregulated pathways. Interestingly, the interaction of mRNA splicing and mRNA splicing-major pathway had the highest score of 719.8167. Maximum change of the activity score between CRC and normal samples appeared in the pathway of DNA replication, which was selected as the seed pathway. Starting with this seed pathway, a pathway set containing 30 dysregulated pathways was obtained with an area under the curve score of 0.8598. The pathway of mRNA splicing, mRNA splicing-major pathway, and RNA polymerase I had the maximum genes of 107. Moreover, we found that these 30 pathways had crosstalks with each other. The results suggest that these dysregulated pathways might be used as biomarkers to diagnose CRC.

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

    Science.gov (United States)

    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. © 2014 The Authors. Genes, Brain and Behavior published by International Behavioural and Neural Genetics Society and John Wiley & Sons Ltd.

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

    Directory of Open Access Journals (Sweden)

    Brian J Capaldo

    Full Text Available 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.

  13. GEP analysis validates high risk MDS and acute myeloid leukemia post MDS mice models and highlights novel dysregulated pathways.

    Science.gov (United States)

    Guerenne, Laura; Beurlet, Stéphanie; Said, Mohamed; Gorombei, Petra; Le Pogam, Carole; Guidez, Fabien; de la Grange, Pierre; Omidvar, Nader; Vanneaux, Valérie; Mills, Ken; Mufti, Ghulam J; Sarda-Mantel, Laure; Noguera, Maria Elena; Pla, Marika; Fenaux, Pierre; Padua, Rose Ann; Chomienne, Christine; Krief, Patricia

    2016-01-27

    In spite of the recent discovery of genetic mutations in most myelodysplasic (MDS) patients, the pathophysiology of these disorders still remains poorly understood, and only few in vivo models are available to help unravel the disease. We performed global specific gene expression profiling and functional pathway analysis in purified Sca1+ cells of two MDS transgenic mouse models that mimic human high-risk MDS (HR-MDS) and acute myeloid leukemia (AML) post MDS, with NRASD12 and BCL2 transgenes under the control of different promoters MRP8NRASD12/tethBCL-2 or MRP8[NRASD12/hBCL-2], respectively. Analysis of dysregulated genes that were unique to the diseased HR-MDS and AML post MDS mice and not their founder mice pointed first to pathways that had previously been reported in MDS patients, including DNA replication/damage/repair, cell cycle, apoptosis, immune responses, and canonical Wnt pathways, further validating these models at the gene expression level. Interestingly, pathways not previously reported in MDS were discovered. These included dysregulated genes of noncanonical Wnt pathways and energy and lipid metabolisms. These dysregulated genes were not only confirmed in a different independent set of BM and spleen Sca1+ cells from the MDS mice but also in MDS CD34+ BM patient samples. These two MDS models may thus provide useful preclinical models to target pathways previously identified in MDS patients and to unravel novel pathways highlighted by this study.

  14. Methods of charged-particle activation analysis

    International Nuclear Information System (INIS)

    Chaudhri, M. Anwar; Chaudhri, M. Nasir; Jabbar, Q.; Nadeem, Q.

    2006-01-01

    The accuracy of Chaudhri's method for charged-particle activation analysis published in J. Radioanal. Chem. (1977) v. 37 p. 243 has been further demonstrated by extensive calculations. The nuclear reactions 12 C(d,n) 13 N, 63 Cu( 3 He,p) 65 Zn, 107 Ag(α,n) 110 In and 208 Pb(d,p) 209 Pb, the cross sections of which were easily available, have been examined for the detection of 12 C, 63 Cu, 107 Ag and 208 Pb, respectively, in matrices of Cu, Zr and Pb, at the bombarding energies of 4 - 22 MeV. The 'standard' is assumed to be in a carbon matrix. It has been clearly demonstrated that Chaudhri's method, which makes the charged particle activation analysis as simple as neutron activation analysis, provides results which are almost identical to, or only about 1-2 % different, from the results obtained using the full 'Activity Equation' involving solving complex integrals. It is valid even when the difference in the average atomic weights of matrices of the standard and the sample is large. (author)

  15. Development and analysis of finite volume methods

    International Nuclear Information System (INIS)

    Omnes, P.

    2010-05-01

    This document is a synthesis of a set of works concerning the development and the analysis of finite volume methods used for the numerical approximation of partial differential equations (PDEs) stemming from physics. In the first part, the document deals with co-localized Godunov type schemes for the Maxwell and wave equations, with a study on the loss of precision of this scheme at low Mach number. In the second part, discrete differential operators are built on fairly general, in particular very distorted or nonconforming, bidimensional meshes. These operators are used to approach the solutions of PDEs modelling diffusion, electro and magneto-statics and electromagnetism by the discrete duality finite volume method (DDFV) on staggered meshes. The third part presents the numerical analysis and some a priori as well as a posteriori error estimations for the discretization of the Laplace equation by the DDFV scheme. The last part is devoted to the order of convergence in the L2 norm of the finite volume approximation of the solution of the Laplace equation in one dimension and on meshes with orthogonality properties in two dimensions. Necessary and sufficient conditions, relatively to the mesh geometry and to the regularity of the data, are provided that ensure the second-order convergence of the method. (author)

  16. Creep analysis by the path function method

    International Nuclear Information System (INIS)

    Akin, J.E.; Pardue, R.M.

    1977-01-01

    The finite element method has become a common analysis procedure for the creep analysis of structures. The most recent programs are designed to handle a general class of material properties and are able to calculate elastic, plastic, and creep components of strain under general loading histories. The constant stress approach is too crude a model to accurately represent the actual behaviour of the stress for large time steps. The true path of a point in the effective stress-effective strain (sigmasup(e)-epsilonsup(c)) plane is often one in which the slope is rapidly changing. Thus the stress level quickly moves away from the initial stress level and then gradually approaches the final one. The result is that the assumed constant stress level quickly becomes inaccurate. What is required is a better method of approximation of the true path in the sigmasup(e)-epsilonsup(c) space. The method described here is called the path function approach because it employs an assumed function to estimate the motion of points in the sigmasup(e)-epsilonsup(c) space. (Auth.)

  17. Earthquake Hazard Analysis Methods: A Review

    Science.gov (United States)

    Sari, A. M.; Fakhrurrozi, A.

    2018-02-01

    One of natural disasters that have significantly impacted on risks and damage is an earthquake. World countries such as China, Japan, and Indonesia are countries located on the active movement of continental plates with more frequent earthquake occurrence compared to other countries. Several methods of earthquake hazard analysis have been done, for example by analyzing seismic zone and earthquake hazard micro-zonation, by using Neo-Deterministic Seismic Hazard Analysis (N-DSHA) method, and by using Remote Sensing. In its application, it is necessary to review the effectiveness of each technique in advance. Considering the efficiency of time and the accuracy of data, remote sensing is used as a reference to the assess earthquake hazard accurately and quickly as it only takes a limited time required in the right decision-making shortly after the disaster. Exposed areas and possibly vulnerable areas due to earthquake hazards can be easily analyzed using remote sensing. Technological developments in remote sensing such as GeoEye-1 provide added value and excellence in the use of remote sensing as one of the methods in the assessment of earthquake risk and damage. Furthermore, the use of this technique is expected to be considered in designing policies for disaster management in particular and can reduce the risk of natural disasters such as earthquakes in Indonesia.

  18. Microarray Study of Pathway Analysis Expression Profile Associated with MicroRNA-29a with Regard to Murine Cholestatic Liver Injuries

    Directory of Open Access Journals (Sweden)

    Sung-Chou Li

    2016-03-01

    Full Text Available Accumulating evidence demonstrates that microRNA-29 (miR-29 expression is prominently decreased in patients with hepatic fibrosis, which consequently stimulates hepatic stellate cells’ (HSCs activation. We used a cDNA microarray study to gain a more comprehensive understanding of genome-wide gene expressions by adjusting miR-29a expression in a bile duct-ligation (BDL animal model. Methods: Using miR-29a transgenic mice and wild-type littermates and applying the BDL mouse model, we characterized the function of miR-29a with regard to cholestatic liver fibrosis. Pathway enrichment analysis and/or specific validation were performed for differentially expressed genes found within the comparisons. Results: Analysis of the microarray data identified a number of differentially expressed genes due to the miR-29a transgene, BDL, or both. Additional pathway enrichment analysis revealed that TGF-β signaling had a significantly differential activated pathway depending on the occurrence of miR-29a overexpression or the lack thereof. Furthermore, overexpression was found to elicit changes in Wnt/β-catenin after BDL. Conclusion: This study verified that an elevated miR-29a level could alleviate liver fibrosis caused by cholestasis. Furthermore, the protective effects of miR-29a correlate with the downregulation of TGF-β and associated with Wnt/β-catenin signal pathway following BDL.

  19. The Biological Connection Markup Language: a SBGN-compliant format for visualization, filtering and analysis of biological pathways.

    Science.gov (United States)

    Beltrame, Luca; Calura, Enrica; Popovici, Razvan R; Rizzetto, Lisa; Guedez, Damariz Rivero; Donato, Michele; Romualdi, Chiara; Draghici, Sorin; Cavalieri, Duccio

    2011-08-01

    Many models and analysis of signaling pathways have been proposed. However, neither of them takes into account that a biological pathway is not a fixed system, but instead it depends on the organism, tissue and cell type as well as on physiological, pathological and experimental conditions. The Biological Connection Markup Language (BCML) is a format to describe, annotate and visualize pathways. BCML is able to store multiple information, permitting a selective view of the pathway as it exists and/or behave in specific organisms, tissues and cells. Furthermore, BCML can be automatically converted into data formats suitable for analysis and into a fully SBGN-compliant graphical representation, making it an important tool that can be used by both computational biologists and 'wet lab' scientists. The XML schema and the BCML software suite are freely available under the LGPL for download at http://bcml.dc-atlas.net. They are implemented in Java and supported on MS Windows, Linux and OS X.

  20. Putative drug and vaccine target protein identification using comparative genomic analysis of KEGG annotated metabolic pathways of Mycoplasma hyopneumoniae.

    Science.gov (United States)

    Damte, Dereje; Suh, Joo-Won; Lee, Seung-Jin; Yohannes, Sileshi Belew; Hossain, Md Akil; Park, Seung-Chun

    2013-07-01

    In the present study, a computational comparative and subtractive genomic/proteomic analysis aimed at the identification of putative therapeutic target and vaccine candidate proteins from Kyoto Encyclopedia of Genes and Genomes (KEGG) annotated metabolic pathways of Mycoplasma hyopneumoniae was performed for drug design and vaccine production pipelines against M.hyopneumoniae. The employed comparative genomic and metabolic pathway analysis with a predefined computational systemic workflow extracted a total of 41 annotated metabolic pathways from KEGG among which five were unique to M. hyopneumoniae. A total of 234 proteins were identified to be involved in these metabolic pathways. Although 125 non homologous and predicted essential proteins were found from the total that could serve as potential drug targets and vaccine candidates, additional prioritizing parameters characterize 21 proteins as vaccine candidate while druggability of each of the identified proteins evaluated by the DrugBank database prioritized 42 proteins suitable for drug targets. Copyright © 2013 Elsevier Inc. All rights reserved.

  1. Bi-directional gene set enrichment and canonical correlation analysis identify key diet-sensitive pathways and biomarkers of metabolic syndrome

    Directory of Open Access Journals (Sweden)

    Gaora Peadar Ó

    2010-10-01

    Full Text Available Abstract Background Currently, a number of bioinformatics methods are available to generate appropriate lists of genes from a microarray experiment. While these lists represent an accurate primary analysis of the data, fewer options exist to contextualise those lists. The development and validation of such methods is crucial to the wider application of microarray technology in the clinical setting. Two key challenges in clinical bioinformatics involve appropriate statistical modelling of dynamic transcriptomic changes, and extraction of clinically relevant meaning from very large datasets. Results Here, we apply an approach to gene set enrichment analysis that allows for detection of bi-directional enrichment within a gene set. Furthermore, we apply canonical correlation analysis and Fisher's exact test, using plasma marker data with known clinical relevance to aid identification of the most important gene and pathway changes in our transcriptomic dataset. After a 28-day dietary intervention with high-CLA beef, a range of plasma markers indicated a marked improvement in the metabolic health of genetically obese mice. Tissue transcriptomic profiles indicated that the effects were most dramatic in liver (1270 genes significantly changed; p Conclusion Bi-directional gene set enrichment analysis more accurately reflects dynamic regulatory behaviour in biochemical pathways, and as such highlighted biologically relevant changes that were not detected using a traditional approach. In such cases where transcriptomic response to treatment is exceptionally large, canonical correlation analysis in conjunction with Fisher's exact test highlights the subset of pathways showing strongest correlation with the clinical markers of interest. In this case, we have identified selenoamino acid metabolism and steroid biosynthesis as key pathways mediating the observed relationship between metabolic health and high-CLA beef. These results indicate that this type of

  2. Point Analysis in Java applied to histological images of the perforant pathway: A user’s account

    OpenAIRE

    Scorcioni, Ruggero; Wright, Susan N.; Card, J. Patrick; Ascoli, Giorgio A.; Barrionuevo, Germán

    2008-01-01

    The freeware Java tool PAJ, created to perform 3D point analysis, was tested in an independent laboratory setting. The input data consisted of images of the hippocampal perforant pathway from serial immunocytochemical localizations of the rat brain in multiple views at different resolutions. The low magnification set (2× objective) comprised the entire perforant pathway, while the high magnification set (100× objective) allowed the identification of individual fibers. A preliminary stereologi...

  3. Multiple Regression Analysis of mRNA-miRNA Associations in Colorectal Cancer Pathway

    Science.gov (United States)

    Wang, Fengfeng; Wong, S. C. Cesar; Chan, Lawrence W. C.; Cho, William C. S.; Yip, S. P.; Yung, Benjamin Y. M.

    2014-01-01

    Background. MicroRNA (miRNA) is a short and endogenous RNA molecule that regulates posttranscriptional gene expression. It is an important factor for tumorigenesis of colorectal cancer (CRC), and a potential biomarker for diagnosis, prognosis, and therapy of CRC. Our objective is to identify the related miRNAs and their associations with genes frequently involved in CRC microsatellite instability (MSI) and chromosomal instability (CIN) signaling pathways. Results. A regression model was adopted to identify the significantly associated miRNAs targeting a set of candidate genes frequently involved in colorectal cancer MSI and CIN pathways. Multiple linear regression analysis was used to construct the model and find the significant mRNA-miRNA associations. We identified three significantly associated mRNA-miRNA pairs: BCL2 was positively associated with miR-16 and SMAD4 was positively associated with miR-567 in the CRC tissue, while MSH6 was positively associated with miR-142-5p in the normal tissue. As for the whole model, BCL2 and SMAD4 models were not significant, and MSH6 model was significant. The significant associations were different in the normal and the CRC tissues. Conclusion. Our results have laid down a solid foundation in exploration of novel CRC mechanisms, and identification of miRNA roles as oncomirs or tumor suppressor mirs in CRC. PMID:24895601

  4. Assessing invasion process through pathway and vector analysis: case of saltcedar (Tamarix spp.

    Directory of Open Access Journals (Sweden)

    Evangelina Natale

    2012-12-01

    Full Text Available Biological invasions are one of the most pervasive environmental threats to native ecosystems worldwide. The spontaneous spread ofsaltcedar is a particular threat to biodiversity conservation in arid and semiarid environments. In Argentina, three species belonging to this genus have been recognized as invaders. The aim of the present study was to identify main dispersal vectors and pathways to refine risk analysis and increase our ability to predict new areas at risk of Tamarix establishment. We surveyed and categorized 223 populations, 39% as invasive, 26% as established, 21% as contained and 14% as detected in nature. Dispersion of saltcedar was found to be associated with watercourses and human-driven disturbances; in addition roads were found to be relevant for the introduction of propagules in newenvironments. Considering the potential impact of saltcedar invasion and that it is an easily wind-dispersed invasive, it is necessary toimplement strategies to monitor dispersal pathways and take actions to eliminate invasion foci, particularly in vulnerable and highconservation value areas.

  5. Allowable residual contamination levels of radionuclides in soil from pathway analysis

    International Nuclear Information System (INIS)

    Nyquist, J.E.; Baes, C.F. III

    1987-01-01

    The Remedial Action Program (RAP) at Oak Ridge National Laboratory will include well drilling, facility upgrades, and other waste management operations likely to involve soils contaminated with radionuclides. A preliminary protocol and generalized criteria for handling contaminated soils is needed to coordinate and plan RAP activities, but there exists only limited information on contaminate nature and distribution at ORNL RAP sites. Furthermore, projections of long-term decommissioning and closure options for these sites are preliminary. They have adapted a pathway analysis model, DECOM, to quantify risks to human health from radionuclides in soil and used it to outline preliminary criteria for determining the fate of contaminated soil produced during RAP activities. They assumed that the site could be available for unrestricted use immediately upon decontamination. The pathways considered are consumption of food grown on the contaminated soil, including direct ingestion of soil from poorly washed vegetables, direct radiation from the ground surface, inhalation of resuspended radioactive soil, and drinking water from a well drilled through or near the contaminated soil. We will discuss the assumptions and simplifications implicit in DECOM, the site-specific data required, and the results of initial calculations for the Oak Ridge Reservation

  6. Enhancement of cordyceps polysaccharide production via biosynthetic pathway analysis in Hirsutella sinensis.

    Science.gov (United States)

    Lin, Shan; Liu, Zhi-Qiang; Baker, Peter James; Yi, Ming; Wu, Hui; Xu, Feng; Teng, Yi; Zheng, Yu-Guo

    2016-11-01

    The addition of various sulfates for enhanced cordyceps polysaccharide (CP) production in submerged cultivation of H. sinensis was investigated, and manganese sulfate was found the most effective. 2mM of manganese sulfate on 0day (d) was investigated as the optimal adding condition, and the CP production reached optimum with 5.33%, increasing by 93.3% compared with the control. Furthermore, the consumption of three main precursors of CP was studied over cultivation under two conditions. Intracellular mannose content decreased by 43.1% throughout 6days cultivation, which corresponded to CP accumulation rate sharply increased from 0 d to 6 d, and mannose was considered as the most preferred precursor for generating CP. Subsequently, mannose biosynthetic pathway was constructed and verified for the first time in H. sinensis, which constituted the important part of CP biosynthesis, and transcriptional levels of the biosynthetic genes were studied. Transcriptional level of gene cpsA was significantly up-regulated 5.35-fold and it was a key gene involved both in mannose and CP biosynthesis. This study demonstrated that manganese sulfate addition is an efficient and simple way to improve CP production. Transcriptional analysis based on biosynthetic pathway was helpful to find key genes and better understand CP biosynthesis. Copyright © 2016 Elsevier B.V. All rights reserved.

  7. Sensitivity analysis of the Two Geometry Method

    International Nuclear Information System (INIS)

    Wichers, V.A.

    1993-09-01

    The Two Geometry Method (TGM) was designed specifically for the verification of the uranium enrichment of low enriched UF 6 gas in the presence of uranium deposits on the pipe walls. Complications can arise if the TGM is applied under extreme conditions, such as deposits larger than several times the gas activity, small pipe diameters less than 40 mm and low pressures less than 150 Pa. This report presents a comprehensive sensitivity analysis of the TGM. The impact of the various sources of uncertainty on the performance of the method is discussed. The application to a practical case is based on worst case conditions with regards to the measurement conditions, and on realistic conditions with respect to the false alarm probability and the non detection probability. Monte Carlo calculations were used to evaluate the sensitivity for sources of uncertainty which are experimentally inaccessible. (orig.)

  8. Blood proteins analysis by Raman spectroscopy method

    Science.gov (United States)

    Artemyev, D. N.; Bratchenko, I. A.; Khristoforova, Yu. A.; Lykina, A. A.; Myakinin, O. O.; Kuzmina, T. P.; Davydkin, I. L.; Zakharov, V. P.

    2016-04-01

    This work is devoted to study the possibility of plasma proteins (albumin, globulins) concentration measurement using Raman spectroscopy setup. The blood plasma and whole blood were studied in this research. The obtained Raman spectra showed significant variation of intensities of certain spectral bands 940, 1005, 1330, 1450 and 1650 cm-1 for different protein fractions. Partial least squares regression analysis was used for determination of correlation coefficients. We have shown that the proposed method represents the structure and biochemical composition of major blood proteins.

  9. Moessbauer lineshape analysis by the DISPA method

    International Nuclear Information System (INIS)

    Miglierini, M.; Sitek, J.

    1986-01-01

    To evaluate the Moessbauer spectral parameters and hence, the structural and magnetic properties the lineshape should be known. A plot of dispersion versus absorption (DISPA plot) for a pure Lorentzian gives a perfect circle. Directions and magnitudes of DISPA distortions from this reference circle point out the kind of line-broadening mechanism observed. A possibility of the application of the DISPA technique in the Moessbauer lineshape analysis is dealt with in this paper. The method is verified on Moessbauer spectra of sodium nitroprusside, natural iron, and stainless steel. The lineshape of an amorphous metallic alloy Fe 40 Ni 40 B 20 is studied by means of the DISPA plots. (author)

  10. Electromagnetic compatibility methods, analysis, circuits, and measurement

    CERN Document Server

    Weston, David A

    2016-01-01

    Revised, updated, and expanded, Electromagnetic Compatibility: Methods, Analysis, Circuits, and Measurement, Third Edition provides comprehensive practical coverage of the design, problem solving, and testing of electromagnetic compatibility (EMC) in electrical and electronic equipment and systems. This new edition provides novel information on theory, applications, evaluations, electromagnetic computational programs, and prediction techniques available. With sixty-nine schematics providing examples for circuit level electromagnetic interference (EMI) hardening and cost effective EMI problem solving, this book also includes 1130 illustrations and tables. Including extensive data on components and their correct implementation, the myths, misapplication, misconceptions, and fallacies that are common when discussing EMC/EMI will also be addressed and corrected.

  11. Method and apparatus for simultaneous spectroelectrochemical analysis

    Science.gov (United States)

    Chatterjee, Sayandev; Bryan, Samuel A; Schroll, Cynthia A; Heineman, William R

    2013-11-19

    An apparatus and method of simultaneous spectroelectrochemical analysis is disclosed. A transparent surface is provided. An analyte solution on the transparent surface is contacted with a working electrode and at least one other electrode. Light from a light source is focused on either a surface of the working electrode or the analyte solution. The light reflected from either the surface of the working electrode or the analyte solution is detected. The potential of the working electrode is adjusted, and spectroscopic changes of the analyte solution that occur with changes in thermodynamic potentials are monitored.

  12. An algorithm for modularization of MAPK and calcium signaling pathways: comparative analysis among different species.

    Science.gov (United States)

    Nayak, Losiana; De, Rajat K

    2007-12-01

    Signaling pathways are large complex biochemical networks. It is difficult to analyze the underlying mechanism of such networks as a whole. In the present article, we have proposed an algorithm for modularization of signal transduction pathways. Unlike studying a signaling pathway as a whole, this enables one to study the individual modules (less complex smaller units) easily and hence to study the entire pathway better. A comparative study of modules belonging to different species (for the same signaling pathway) has been made, which gives an overall idea about development of the signaling pathways over the taken set of species of calcium and MAPK signaling pathways. The superior performance, in terms of biological significance, of the proposed algorithm over an existing community finding algorithm of Newman [Newman MEJ. Modularity and community structure in networks. Proc Natl Acad Sci USA 2006;103(23):8577-82] has been demonstrated using the aforesaid pathways of H. sapiens.

  13. Genetic analysis of pathway regulation for enhancing branched-chain amino acid biosynthesis in plants

    KAUST Repository

    Chen, Hao

    2010-08-01

    The branched-chain amino acids (BCAAs) valine, leucine and isoleucine are essential amino acids that play critical roles in animal growth and development. Animals cannot synthesize these amino acids and must obtain them from their diet. Plants are the ultimate source of these essential nutrients, and they synthesize BCAAs through a conserved pathway that is inhibited by its end products. This feedback inhibition has prevented scientists from engineering plants that accumulate high levels of BCAAs by simply over-expressing the respective biosynthetic genes. To identify components critical for this feedback regulation, we performed a genetic screen for Arabidopsis mutants that exhibit enhanced resistance to BCAAs. Multiple dominant allelic mutations in the VALINE-TOLERANT 1 (VAT1) gene were identified that conferred plant resistance to valine inhibition. Map-based cloning revealed that VAT1 encodes a regulatory subunit of acetohydroxy acid synthase (AHAS), the first committed enzyme in the BCAA biosynthesis pathway. The VAT1 gene is highly expressed in young, rapidly growing tissues. When reconstituted with the catalytic subunit in vitro, the vat1 mutant-containing AHAS holoenzyme exhibits increased resistance to valine. Importantly, transgenic plants expressing the mutated vat1 gene exhibit valine tolerance and accumulate higher levels of BCAAs. Our studies not only uncovered regulatory characteristics of plant AHAS, but also identified a method to enhance BCAA accumulation in crop plants that will significantly enhance the nutritional value of food and feed. © 2010 Blackwell Publishing Ltd.

  14. Pathway confirmation and flux analysis of central metabolic pathways in Desulfovibrio vulgaris Hildenborough using Gas Chromatography-Mass Spectrometry and Fourier Transform-Ion Cyclotron Resonance Mass Spectrometry

    International Nuclear Information System (INIS)

    Tang, Yinjie; Pingitore, Francesco; Mukhopadhyay, Aindrila; Phan, Richard; Hazen, Terry C.; Keasling, Jay D.

    2007-01-01

    Flux distribution in central metabolic pathways of Desulfovibrio vulgaris Hildenborough was examined using 13C tracer experiments. Consistent with the current genome annotation and independent evidence from enzyme activity assays, the isotopomer results from both GC-MS and Fourier Transform-Ion Cyclotron Resonance mass spectrometry (FT-ICR MS) indicate the lack of oxidatively functional TCA cycle and an incomplete pentose phosphate pathway. Results from this study suggest that fluxes through both pathways are limited to biosynthesis. The data also indicate that >80 percent of the lactate was converted to acetate and the reactions involved are the primary route of energy production (NAD(P)H and ATP production). Independent of the TCA cycle, direct cleavage of acetyl-CoA to CO and 5,10-methyl-THF also leads to production of NADH and ATP. Although the genome annotation implicates a ferredoxin-dependent oxoglutarate synthase, isotopic evidence does not support flux through this reaction in either the oxidative or reductive mode; therefore, the TCA cycle is incomplete. FT-ICR MS was used to locate the labeled carbon distribution in aspartate and glutamate and confirmed the presence of an atypical enzyme for citrate formation suggested in previous reports (the citrate synthesized by this enzyme is the isotopic antipode of the citrate synthesized by the (S)-citrate synthase). These findings enable a better understanding of the relation between genome annotation and actual metabolic pathways in D. vulgaris, and also demonstrate FT-ICR MS as a powerful tool for isotopomer analysis, overcoming problems in both GC-MS and NMR spectroscopy

  15. Coloured Petri Nets: Basic Concepts, Analysis Methods and Practical Use. Vol. 2, Analysis Methods

    DEFF Research Database (Denmark)

    Jensen, Kurt

    ideas behind the analysis methods are described as well as the mathematics on which they are based and also how the methods are supported by computer tools. Some parts of the volume are theoretical while others are application oriented. The purpose of the volume is to teach the reader how to use......This three-volume work presents a coherent description of the theoretical and practical aspects of coloured Petri nets (CP-nets). The second volume contains a detailed presentation of the analysis methods for CP-nets. They allow the modeller to investigate dynamic properties of CP-nets. The main...... the formal analysis methods, which does not require a deep understanding of the underlying mathematical theory....

  16. Spectral analysis methods for vehicle interior vibro-acoustics identification

    Science.gov (United States)

    Hosseini Fouladi, Mohammad; Nor, Mohd. Jailani Mohd.; Ariffin, Ahmad Kamal

    2009-02-01

    Noise has various effects on comfort, performance and health of human. Sound are analysed by human brain based on the frequencies and amplitudes. In a dynamic system, transmission of sound and vibrations depend on frequency and direction of the input motion and characteristics of the output. It is imperative that automotive manufacturers invest a lot of effort and money to improve and enhance the vibro-acoustics performance of their products. The enhancement effort may be very difficult and time-consuming if one relies only on 'trial and error' method without prior knowledge about the sources itself. Complex noise inside a vehicle cabin originated from various sources and travel through many pathways. First stage of sound quality refinement is to find the source. It is vital for automotive engineers to identify the dominant noise sources such as engine noise, exhaust noise and noise due to vibration transmission inside of vehicle. The purpose of this paper is to find the vibro-acoustical sources of noise in a passenger vehicle compartment. The implementation of spectral analysis method is much faster than the 'trial and error' methods in which, parts should be separated to measure the transfer functions. Also by using spectral analysis method, signals can be recorded in real operational conditions which conduce to more consistent results. A multi-channel analyser is utilised to measure and record the vibro-acoustical signals. Computational algorithms are also employed to identify contribution of various sources towards the measured interior signal. These achievements can be utilised to detect, control and optimise interior noise performance of road transport vehicles.

  17. Metabolic control analysis of biochemical pathways based on a thermokinetic description of reaction rates

    DEFF Research Database (Denmark)

    Nielsen, Jens Bredal

    1997-01-01

    Metabolic control analysis is a powerful technique for the evaluation of flux control within biochemical pathways. Its foundation is the elasticity coefficients and the flux control coefficients (FCCs). On the basis of a thermokinetic description of reaction rates it is here shown...... that the elasticity coefficients can be calculated directly from the pool levels of metabolites at steady state. The only requirement is that one thermodynamic parameter be known, namely the reaction affinity at the intercept of the tangent in the inflection point of the curve of reaction rate against reaction...... of the thermokinetic description of reaction rates to include the influence of effecters. Here the reaction rate is written as a linear function of the logarithm of the metabolite concentrations. With this type of rate function it is shown that the approach of Delgado and Liao [Biochem. J. (1992) 282, 919-927] can...

  18. A probabilistic generative model for quantification of DNA modifications enables analysis of demethylation pathways.

    Science.gov (United States)

    Äijö, Tarmo; Huang, Yun; Mannerström, Henrik; Chavez, Lukas; Tsagaratou, Ageliki; Rao, Anjana; Lähdesmäki, Harri

    2016-03-14

    We present a generative model, Lux, to quantify DNA methylation modifications from any combination of bisulfite sequencing approaches, including reduced, oxidative, TET-assisted, chemical-modification assisted, and methylase-assisted bisulfite sequencing data. Lux models all cytosine modifications (C, 5mC, 5hmC, 5fC, and 5caC) simultaneously together with experimental parameters, including bisulfite conversion and oxidation efficiencies, as well as various chemical labeling and protection steps. We show that Lux improves the quantification and comparison of cytosine modification levels and that Lux can process any oxidized methylcytosine sequencing data sets to quantify all cytosine modifications. Analysis of targeted data from Tet2-knockdown embryonic stem cells and T cells during development demonstrates DNA modification quantification at unprecedented detail, quantifies active demethylation pathways and reveals 5hmC localization in putative regulatory regions.

  19. Economic analysis of alternative LLW disposal methods

    International Nuclear Information System (INIS)

    Foutes, C.E.; Queenan, C.J. III

    1987-01-01

    The Environmental Protection Agency (EPA) has evaluated the costs and benefits of alternative disposal technologies as part of its program to develop generally applicable environmental standards for the land disposal of low-level radioactive waste (LLW). Costs, population health effects and Critical Population Group (CPG) exposures resulting from alternative waste treatment and disposal methods were evaluated both in absolute terms and also relative to a base case (current practice). Incremental costs of the standard included costs for packaging, processing, transportation, and burial of waste. Benefits are defined in terms of reductions in the general population health risk (expected fatal cancers and genetic effects) evaluated over 10,000 years. A cost-effectiveness ratio, defined as the incremental cost per avoided health effect, was calculated for each alternative standard. The cost-effectiveness analysis took into account a number of waste streams, hydrogeologic and climatic region settings, and waste treatment and disposal methods. This paper describes the alternatives considered and preliminary results of the cost-effectiveness analysis. 15 references, 7 figures, 3 tables

  20. Analysis of methods. [information systems evolution environment

    Science.gov (United States)

    Mayer, Richard J. (Editor); Ackley, Keith A.; Wells, M. Sue; Mayer, Paula S. D.; Blinn, Thomas M.; Decker, Louis P.; Toland, Joel A.; Crump, J. Wesley; Menzel, Christopher P.; Bodenmiller, Charles A.

    1991-01-01

    Information is one of an organization's most important assets. For this reason the development and maintenance of an integrated information system environment is one of the most important functions within a large organization. The Integrated Information Systems Evolution Environment (IISEE) project has as one of its primary goals a computerized solution to the difficulties involved in the development of integrated information systems. To develop such an environment a thorough understanding of the enterprise's information needs and requirements is of paramount importance. This document is the current release of the research performed by the Integrated Development Support Environment (IDSE) Research Team in support of the IISEE project. Research indicates that an integral part of any information system environment would be multiple modeling methods to support the management of the organization's information. Automated tool support for these methods is necessary to facilitate their use in an integrated environment. An integrated environment makes it necessary to maintain an integrated database which contains the different kinds of models developed under the various methodologies. In addition, to speed the process of development of models, a procedure or technique is needed to allow automatic translation from one methodology's representation to another while maintaining the integrity of both. The purpose for the analysis of the modeling methods included in this document is to examine these methods with the goal being to include them in an integrated development support environment. To accomplish this and to develop a method for allowing intra-methodology and inter-methodology model element reuse, a thorough understanding of multiple modeling methodologies is necessary. Currently the IDSE Research Team is investigating the family of Integrated Computer Aided Manufacturing (ICAM) DEFinition (IDEF) languages IDEF(0), IDEF(1), and IDEF(1x), as well as ENALIM, Entity

  1. Chapter 11. Community analysis-based methods

    Energy Technology Data Exchange (ETDEWEB)

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

    2010-05-01

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

  2. Variant allele frequency enrichment analysis in vitro reveals sonic hedgehog pathway to impede sustained temozolomide response in GBM.

    Science.gov (United States)

    Biswas, Nidhan K; Chandra, Vikas; Sarkar-Roy, Neeta; Das, Tapojyoti; Bhattacharya, Rabindra N; Tripathy, Laxmi N; Basu, Sunandan K; Kumar, Shantanu; Das, Subrata; Chatterjee, Ankita; Mukherjee, Ankur; Basu, Pryiadarshi; Maitra, Arindam; Chattopadhyay, Ansuman; Basu, Analabha; Dhara, Surajit

    2015-01-21

    Neoplastic cells of Glioblastoma multiforme (GBM) may or may not show sustained response to temozolomide (TMZ) chemotherapy. We hypothesize that TMZ chemotherapy response in GBM is predetermined in its neoplastic clones via a specific set of mutations that alter relevant pathways. We describe exome-wide enrichment of variant allele frequencies (VAFs) in neurospheres displaying contrasting phenotypes of sustained versus reversible TMZ-responses in vitro. Enrichment of VAFs was found on genes ST5, RP6KA1 and PRKDC in cells showing sustained TMZ-effect whereas on genes FREM2, AASDH and STK36, in cells showing reversible TMZ-effect. Ingenuity pathway analysis (IPA) revealed that these genes alter cell-cycle, G2/M-checkpoint-regulation and NHEJ pathways in sustained TMZ-effect cells whereas the lysine-II&V/phenylalanine degradation and sonic hedgehog (Hh) pathways in reversible TMZ-effect cells. Next, we validated the likely involvement of the Hh-pathway in TMZ-response on additional GBM neurospheres as well as on GBM patients, by extracting RNA-sequencing-based gene expression data from the TCGA-GBM database. Finally, we demonstrated TMZ-sensitization of a TMZ non-responder neurosphere in vitro by treating them with the FDA-approved pharmacological Hh-pathway inhibitor vismodegib. Altogether, our results indicate that the Hh-pathway impedes sustained TMZ-response in GBM and could be a potential therapeutic target to enhance TMZ-response in this malignancy.

  3. 3D analysis methods - Study and seminar

    International Nuclear Information System (INIS)

    Daaviittila, A.

    2003-10-01

    The first part of the report results from a study that was performed as a Nordic co-operation activity with active participation from Studsvik Scandpower and Westinghouse Atom in Sweden, and VTT in Finland. The purpose of the study was to identify and investigate the effects rising from using the 3D transient com-puter codes in BWR safety analysis, and their influence on the transient analysis methodology. One of the main questions involves the critical power ratio (CPR) calculation methodology. The present way, where the CPR calculation is per-formed with a separate hot channel calculation, can be artificially conservative. In the investigated cases, no dramatic minimum CPR effect coming from the 3D calculation is apparent. Some cases show some decrease in the transient change of minimum CPR with the 3D calculation, which confirms the general thinking that the 1D calculation is conservative. On the other hand, the observed effect on neutron flux behaviour is quite large. In a slower transient the 3D effect might be stronger. The second part of the report is a summary of a related seminar that was held on the 3D analysis methods. The seminar was sponsored by the Reactor Safety part (NKS-R) of the Nordic Nuclear Safety Research Programme (NKS). (au)

  4. Generalized Analysis of a Distribution Separation Method

    Directory of Open Access Journals (Sweden)

    Peng Zhang

    2016-04-01

    Full Text Available Separating two probability distributions from a mixture model that is made up of the combinations of the two is essential to a wide range of applications. For example, in information retrieval (IR, there often exists a mixture distribution consisting of a relevance distribution that we need to estimate and an irrelevance distribution that we hope to get rid of. Recently, a distribution separation method (DSM was proposed to approximate the relevance distribution, by separating a seed irrelevance distribution from the mixture distribution. It was successfully applied to an IR task, namely pseudo-relevance feedback (PRF, where the query expansion model is often a mixture term distribution. Although initially developed in the context of IR, DSM is indeed a general mathematical formulation for probability distribution separation. Thus, it is important to further generalize its basic analysis and to explore its connections to other related methods. In this article, we first extend DSM’s theoretical analysis, which was originally based on the Pearson correlation coefficient, to entropy-related measures, including the KL-divergence (Kullback–Leibler divergence, the symmetrized KL-divergence and the JS-divergence (Jensen–Shannon divergence. Second, we investigate the distribution separation idea in a well-known method, namely the mixture model feedback (MMF approach. We prove that MMF also complies with the linear combination assumption, and then, DSM’s linear separation algorithm can largely simplify the EM algorithm in MMF. These theoretical analyses, as well as further empirical evaluation results demonstrate the advantages of our DSM approach.

  5. Method development for trace and ultratrace analysis

    International Nuclear Information System (INIS)

    Anon.

    1992-01-01

    Method development, that is, selection of a mode of chromatography and the right column and mobile-phase combination for trace and ultratrace analysis, requires several main considerations. The method should be useful for resolving various trace and ultratrace components present in the sample. If the nature of these components is known, the choice of method may be straightforward, that is, a selection can be made from the following modes of HPLC: (1) adsorption chromatography; (2) normal-phase chromatography; (3) reversed-phase chromatography; (4) ion-pair chromatography; (5) ion-exchange chromatography; (6) ion chromatography. Unfortunately, the nature of all of the components is frequently unknown. However, several intelligent judgments can be made on the nature of impurities. This chapter deals with some basic approaches to mobile-phase selection and optimization. More detailed information may be found in basic texts. Techniques for separation of high-molecular-weight compounds (macromolecules) and chiral compounds may be found elsewhere. Mainly compounds with molecular weight lower than 2,000 are discussed here. 123 refs

  6. Novel Method of Production Decline Analysis

    Science.gov (United States)

    Xie, Shan; Lan, Yifei; He, Lei; Jiao, Yang; Wu, Yong

    2018-02-01

    ARPS decline curves is the most commonly used in oil and gas field due to its minimal data requirements and ease application. And prediction of production decline which is based on ARPS analysis rely on known decline type. However, when coefficient index are very approximate under different decline type, it is difficult to directly recognize decline trend of matched curves. Due to difficulties above, based on simulation results of multi-factor response experiments, a new dynamic decline prediction model is introduced with using multiple linear regression of influence factors. First of all, according to study of effect factors of production decline, interaction experimental schemes are designed. Based on simulated results, annual decline rate is predicted by decline model. Moreover, the new method is applied in A gas filed of Ordos Basin as example to illustrate reliability. The result commit that the new model can directly predict decline tendency without needing recognize decline style. From arithmetic aspect, it also take advantage of high veracity. Finally, the new method improves the evaluation method of gas well production decline in low permeability gas reservoir, which also provides technical support for further understanding of tight gas field development laws.

  7. Phylogenetic analysis using parsimony and likelihood methods.

    Science.gov (United States)

    Yang, Z

    1996-02-01

    The assumptions underlying the maximum-parsimony (MP) method of phylogenetic tree reconstruction were intuitively examined by studying the way the method works. Computer simulations were performed to corroborate the intuitive examination. Parsimony appears to involve very stringent assumptions concerning the process of sequence evolution, such as constancy of substitution rates between nucleotides, constancy of rates across nucleotide sites, and equal branch lengths in the tree. For practical data analysis, the requirement of equal branch lengths means similar substitution rates among lineages (the existence of an approximate molecular clock), relatively long interior branches, and also few species in the data. However, a small amount of evolution is neither a necessary nor a sufficient requirement of the method. The difficulties involved in the application of current statistical estimation theory to tree reconstruction were discussed, and it was suggested that the approach proposed by Felsenstein (1981, J. Mol. Evol. 17: 368-376) for topology estimation, as well as its many variations and extensions, differs fundamentally from the maximum likelihood estimation of a conventional statistical parameter. Evidence was presented showing that the Felsenstein approach does not share the asymptotic efficiency of the maximum likelihood estimator of a statistical parameter. Computer simulations were performed to study the probability that MP recovers the true tree under a hierarchy of models of nucleotide substitution; its performance relative to the likelihood method was especially noted. The results appeared to support the intuitive examination of the assumptions underlying MP. When a simple model of nucleotide substitution was assumed to generate data, the probability that MP recovers the true topology could be as high as, or even higher than, that for the likelihood method. When the assumed model became more complex and realistic, e.g., when substitution rates were

  8. A Method to Evaluate Critical Factors for Successful Implementation of Clinical Pathways.

    Science.gov (United States)

    Dong, W; Huang, Z

    2015-01-01

    Clinical pathways (CPs) have been viewed as a multidisciplinary tool to improve the quality and efficiency of evidence-based care. Despite widespread enthusiasm for CPs, research has shown that many CP initiatives are unsuccessful. To this end, this study provides a methodology to evaluate critical success factors (CSFs) that can aid healthcare organizations to achieve successful CP implementation. This study presents a new approach to evaluate CP implementation CSFs, with the aims being: (1) to identify CSFs for implementation of CPs through a comprehensive literature review and interviews with collaborative experts; (2) to use a filed study data with a robust fuzzy DEMATEL (the decision making trial and evaluation laboratory) approach to visualize the structure of complicated causal relationships between CSFs and obtain the influence level of these factors. The filed study data is provided by ten clinical experts of a Chinese hospital. 23 identified CSF factors which are initially identified through a review of the literature and interviews with collaborative experts. Then, a number of direct and indirect relationships are derived from the data such that different perceptions can be integrated into a compromised cause and effect model of CP implementation. The results indicate that the proposed approach can systematically evaluate CSFs and realize the importance of each factor such that the most common causes of failure of CP implementation could be eliminated or avoided. Therefore, the tool proposed would help healthcare organizations to manage CP implementation in a more effective and proactive way.

  9. Phase analysis in the Wolff-Parkinson-White syndrome with surgically proven accessory conduction pathways: concise communication

    International Nuclear Information System (INIS)

    Nakajima, K.; Bunko, H.; Tada, A.; Taki, J.; Tonami, N.; Hisada, K.; Misaki, T.; Iwa, T.

    1984-01-01

    Twenty-one patients with the Wolff-Parkinson-White (WPW) syndrome who underwent surgical division of the accessory conduction pathway (ACP) were studied by gated blood-pool scintigraphy. In each case, a functional image of the phase was generated, based on the fundamental frequency of the Fourier transform. The location of the ACP was confirmed by electrophysiologic study, epicardial mapping, and surgery. Phase analysis identified the side of preexcitation correctly in 16 out of 20 patients with WPW syndrome with a delta wave. All patients with right-cardiac type (N=9) had initial contraction in the right ventricle (RV). In patients with left-cardiac type (N=10), six had initial movement in the left ventricle (LV); but in the other four the ACPs in the anterior or lateral wall of the left ventricle (LV) could not be detected. In patients with multiple ACPs (N=2), one right-cardiac type had initial contraction in the RV, while in the other (with an intermittent WPW syndrome) the ACP was not detected. These observations indicate that abnormal wall motion is associated with the conduction anomalies of the WPW syndrome. We conclude that phase analysis can correctly identify the side of initial contraction in the WPW syndrome before and after surgery. However, as a method of preoperative study, it seems difficult to determine the precise site of the ACP by phase analysis alone

  10. Phase analysis in the Wolff-Parkinson-White syndrome with surgically proven accessory conduction pathways: concise communication

    Energy Technology Data Exchange (ETDEWEB)

    Nakajima, K.; Bunko, H.; Tada, A.; Taki, J.; Tonami, N.; Hisada, K.; Misaki, T.; Iwa, T.

    1984-01-01

    Twenty-one patients with the Wolff-Parkinson-White (WPW) syndrome who underwent surgical division of the accessory conduction pathway (ACP) were studied by gated blood-pool scintigraphy. In each case, a functional image of the phase was generated, based on the fundamental frequency of the Fourier transform. The location of the ACP was confirmed by electrophysiologic study, epicardial mapping, and surgery. Phase analysis identified the side of preexcitation correctly in 16 out of 20 patients with WPW syndrome with a delta wave. All patients with right-cardiac type (N=9) had initial contraction in the right ventricle (RV). In patients with left-cardiac type (N=10), six had initial movement in the left ventricle (LV); but in the other four the ACPs in the anterior or lateral wall of the left ventricle (LV) could not be detected. In patients with multiple ACPs (N=2), one right-cardiac type had initial contraction in the RV, while in the other (with an intermittent WPW syndrome) the ACP was not detected. These observations indicate that abnormal wall motion is associated with the conduction anomalies of the WPW syndrome. We conclude that phase analysis can correctly identify the side of initial contraction in the WPW syndrome before and after surgery. However, as a method of preoperative study, it seems difficult to determine the precise site of the ACP by phase analysis alone.

  11. External event analysis methods for NUREG-1150

    International Nuclear Information System (INIS)

    Bohn, M.P.; Lambright, J.A.

    1989-01-01

    The US Nuclear Regulatory Commission is sponsoring probabilistic risk assessments of six operating commercial nuclear power plants as part of a major update of the understanding of risk as provided by the original WASH-1400 risk assessments. In contrast to the WASH-1400 studies, at least two of the NUREG-1150 risk assessments will include an analysis of risks due to earthquakes, fires, floods, etc., which are collectively known as eternal events. This paper summarizes the methods to be used in the external event analysis for NUREG-1150 and the results obtained to date. The two plants for which external events are being considered are Surry and Peach Bottom, a PWR and BWR respectively. The external event analyses (through core damage frequency calculations) were completed in June 1989, with final documentation available in September. In contrast to most past external event analyses, wherein rudimentary systems models were developed reflecting each external event under consideration, the simplified NUREG-1150 analyses are based on the availability of the full internal event PRA systems models (event trees and fault trees) and make use of extensive computer-aided screening to reduce them to sequence cut sets important to each external event. This provides two major advantages in that consistency and scrutability with respect to the internal event analysis is achieved, and the full gamut of random and test/maintenance unavailabilities are automatically included, while only those probabilistically important survive the screening process. Thus, full benefit of the internal event analysis is obtained by performing the internal and external event analyses sequentially

  12. Integrated Enrichment Analysis of Variants and Pathways in Genome-Wide Association Studies Indicates Central Role for IL-2 Signaling Genes in Type 1 Diabetes, and Cytokine Signaling Genes in Crohn's Disease

    Science.gov (United States)

    Carbonetto, Peter; Stephens, Matthew

    2013-01-01

    Pathway analyses of genome-wide association studies aggregate information over sets of related genes, such as genes in common pathways, to identify gene sets that are enriched for variants associated with disease. We develop a model-based approach to pathway analysis, and apply this approach to data from the Wellcome Trust Case Control Consortium (WTCCC) studies. Our method offers several benefits over existing approaches. First, our method not only interrogates pathways for enrichment of disease associations, but also estimates the level of enrichment, which yields a coherent way to promote variants in enriched pathways, enhancing discovery of genes underlying disease. Second, our approach allows for multiple enriched pathways, a feature that leads to novel findings in two diseases where the major histocompatibility complex (MHC) is a major determinant of disease susceptibility. Third, by modeling disease as the combined effect of multiple markers, our method automatically accounts for linkage disequilibrium among variants. Interrogation of pathways from eight pathway databases yields strong support for enriched pathways, indicating links between Crohn's disease (CD) and cytokine-driven networks that modulate immune responses; between rheumatoid arthritis (RA) and “Measles” pathway genes involved in immune responses triggered by measles infection; and between type 1 diabetes (T1D) and IL2-mediated signaling genes. Prioritizing variants in these enriched pathways yields many additional putative disease associations compared to analyses without enrichment. For CD and RA, 7 of 8 additional non-MHC associations are corroborated by other studies, providing validation for our approach. For T1D, prioritization of IL-2 signaling genes yields strong evidence for 7 additional non-MHC candidate disease loci, as well as suggestive evidence for several more. Of the 7 strongest associations, 4 are validated by other studies, and 3 (near IL-2 signaling genes RAF1, MAPK14

  13. Spectral Analysis Methods of Social Networks

    Directory of Open Access Journals (Sweden)

    P. G. Klyucharev

    2017-01-01

    Full Text Available Online social networks (such as Facebook, Twitter, VKontakte, etc. being an important channel for disseminating information are often used to arrange an impact on the social consciousness for various purposes - from advertising products or services to the full-scale information war thereby making them to be a very relevant object of research. The paper reviewed the analysis methods of social networks (primarily, online, based on the spectral theory of graphs. Such methods use the spectrum of the social graph, i.e. a set of eigenvalues of its adjacency matrix, and also the eigenvectors of the adjacency matrix.Described measures of centrality (in particular, centrality based on the eigenvector and PageRank, which reflect a degree of impact one or another user of the social network has. A very popular PageRank measure uses, as a measure of centrality, the graph vertices, the final probabilities of the Markov chain, whose matrix of transition probabilities is calculated on the basis of the adjacency matrix of the social graph. The vector of final probabilities is an eigenvector of the matrix of transition probabilities.Presented a method of dividing the graph vertices into two groups. It is based on maximizing the network modularity by computing the eigenvector of the modularity matrix.Considered a method for detecting bots based on the non-randomness measure of a graph to be computed using the spectral coordinates of vertices - sets of eigenvector components of the adjacency matrix of a social graph.In general, there are a number of algorithms to analyse social networks based on the spectral theory of graphs. These algorithms show very good results, but their disadvantage is the relatively high (albeit polynomial computational complexity for large graphs.At the same time it is obvious that the practical application capacity of the spectral graph theory methods is still underestimated, and it may be used as a basis to develop new methods.The work

  14. Parameter-free methods distinguish Wnt pathway models and guide design of experiments

    KAUST Repository

    MacLean, Adam L.; Rosen, Zvi; Byrne, Helen M.; Harrington, Heather A.

    2015-01-01

    models can fit this time course. We appeal to algebraic methods (concepts from chemical reaction network theory and matroid theory) to analyze the models without recourse to specific parameter values. These approaches provide insight into aspects of Wnt

  15. Method and tool for network vulnerability analysis

    Science.gov (United States)

    Swiler, Laura Painton [Albuquerque, NM; Phillips, Cynthia A [Albuquerque, NM

    2006-03-14

    A computer system analysis tool and method that will allow for qualitative and quantitative assessment of security attributes and vulnerabilities in systems including computer networks. The invention is based on generation of attack graphs wherein each node represents a possible attack state and each edge represents a change in state caused by a single action taken by an attacker or unwitting assistant. Edges are weighted using metrics such as attacker effort, likelihood of attack success, or time to succeed. Generation of an attack graph is accomplished by matching information about attack requirements (specified in "attack templates") to information about computer system configuration (contained in a configuration file that can be updated to reflect system changes occurring during the course of an attack) and assumed attacker capabilities (reflected in "attacker profiles"). High risk attack paths, which correspond to those considered suited to application of attack countermeasures given limited resources for applying countermeasures, are identified by finding "epsilon optimal paths."

  16. In vivo kinetic analysis of the penicillin biosynthesis pathway using PAA stimulus response experiments.

    Science.gov (United States)

    Deshmukh, Amit T; Verheijen, Peter J T; Maleki Seifar, Reza; Heijnen, Joseph J; van Gulik, Walter M

    2015-11-01

    In this study we combined experimentation with mathematical modeling to unravel the in vivo kinetic properties of the enzymes and transporters of the penicillin biosynthesis pathway in a high yielding Penicillium chrysogenum strain. The experiment consisted of a step response experiment with the side chain precursor phenyl acetic acid (PAA) in a glucose-limited chemostat. The metabolite data showed that in the absence of PAA all penicillin pathway enzymes were expressed, leading to the production of a significant amount of 6-aminopenicillanic acid (6APA) as end product. After the stepwise perturbation with PAA, the pathway produced PenG within seconds. From the extra- and intracellular metabolite measurements, hypotheses for the secretion mechanisms of penicillin pathway metabolites were derived. A dynamic model of the penicillin biosynthesis pathway was then constructed that included the formation and transport over the cytoplasmic membrane of pathway intermediates, PAA and the product penicillin-G (PenG). The model parameters and changes in the enzyme levels of the penicillin biosynthesis pathway under in vivo conditions were simultaneously estimated using experimental data obtained at three different timescales (seconds, minutes, hours). The model was applied to determine changes in the penicillin pathway enzymes in time, calculate fluxes and analyze the flux control of the pathway. This led to a reassessment of the in vivo behavior of the pathway enzymes and in particular Acyl-CoA:Isopenicillin N Acyltransferase (AT). Copyright © 2015 International Metabolic Engineering Society. Published by Elsevier Inc. All rights reserved.

  17. Quantitative Risk Analysis: Method And Process

    Directory of Open Access Journals (Sweden)

    Anass BAYAGA

    2010-03-01

    Full Text Available Recent and past studies (King III report, 2009: 73-75; Stoney 2007;Committee of Sponsoring Organisation-COSO, 2004, Bartell, 2003; Liebenberg and Hoyt, 2003; Reason, 2000; Markowitz 1957 lament that although, the introduction of quantifying risk to enhance degree of objectivity in finance for instance was quite parallel to its development in the manufacturing industry, it is not the same in Higher Education Institution (HEI. In this regard, the objective of the paper was to demonstrate the methods and process of Quantitative Risk Analysis (QRA through likelihood of occurrence of risk (phase I. This paper serves as first of a two-phased study, which sampled hundred (100 risk analysts in a University in the greater Eastern Cape Province of South Africa.The analysis of likelihood of occurrence of risk by logistic regression and percentages were conducted to investigate whether there were a significant difference or not between groups (analyst in respect of QRA.The Hosmer and Lemeshow test was non-significant with a chi-square(X2 =8.181; p = 0.300, which indicated that there was a good model fit, since the data did not significantly deviate from the model. The study concluded that to derive an overall likelihood rating that indicated the probability that a potential risk may be exercised within the construct of an associated threat environment, the following governing factors must be considered: (1 threat source motivation and capability (2 nature of the vulnerability (3 existence and effectiveness of current controls (methods and process.

  18. Genetic variation in the TP53 pathway and bladder cancer risk. a comprehensive analysis.

    Directory of Open Access Journals (Sweden)

    Silvia Pineda

    Full Text Available 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.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.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.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.

  19. Integrative network analysis unveils convergent molecular pathways in Parkinson's disease and diabetes.

    Science.gov (United States)

    Santiago, Jose A; Potashkin, Judith A

    2013-01-01

    Shared dysregulated pathways may contribute to Parkinson's disease and type 2 diabetes, chronic diseases that afflict millions of people worldwide. Despite the evidence provided by epidemiological and gene profiling studies, the molecular and functional networks implicated in both diseases, have not been fully explored. In this study, we used an integrated network approach to investigate the extent to which Parkinson's disease and type 2 diabetes are linked at the molecular level. Using a random walk algorithm within the human functional linkage network we identified a molecular cluster of 478 neighboring genes closely associated with confirmed Parkinson's disease and type 2 diabetes genes. Biological and functional analysis identified the protein serine-threonine kinase activity, MAPK cascade, activation of the immune response, and insulin receptor and lipid signaling as convergent pathways. Integration of results from microarrays studies identified a blood signature comprising seven genes whose expression is dysregulated in Parkinson's disease and type 2 diabetes. Among this group of genes, is the amyloid precursor protein (APP), previously associated with neurodegeneration and insulin regulation. Quantification of RNA from whole blood of 192 samples from two independent clinical trials, the Harvard Biomarker Study (HBS) and the Prognostic Biomarker Study (PROBE), revealed that expression of APP is significantly upregulated in Parkinson's disease patients compared to healthy controls. Assessment of biomarker performance revealed that expression of APP could distinguish Parkinson's disease from healthy individuals with a diagnostic accuracy of 80% in both cohorts of patients. These results provide the first evidence that Parkinson's disease and diabetes are strongly linked at the molecular level and that shared molecular networks provide an additional source for identifying highly sensitive biomarkers. Further, these results suggest for the first time that

  20. Analysis of SNPs and haplotypes in vitamin D pathway genes and renal cancer risk.

    Directory of Open Access Journals (Sweden)

    Sara Karami

    2009-09-01

    Full Text Available In the kidney vitamin D is converted to its active form. Since vitamin D exerts its activity through binding to the nuclear vitamin D receptor (VDR, most genetic studies have primarily focused on variation within this gene. Therefore, analysis of genetic variation in VDR and other vitamin D pathway genes may provide insight into the role of vitamin D in renal cell carcinoma (RCC etiology. RCC cases (N = 777 and controls (N = 1,035 were genotyped to investigate the relationship between RCC risk and variation in eight target genes. Minimum-p-value permutation (Min-P tests were used to identify genes associated with risk. A three single nucleotide polymorphism (SNP sliding window was used to identify chromosomal regions with a False Discovery Rate of <10%, where subsequently, haplotype relative risks were computed in Haplostats. Min-P values showed that VDR (p-value = 0.02 and retinoid-X-receptor-alpha (RXRA (p-value = 0.10 were associated with RCC risk. Within VDR, three haplotypes across two chromosomal regions of interest were identified. The first region, located within intron 2, contained two haplotypes that increased RCC risk by approximately 25%. The second region included a haplotype (rs2239179, rs12717991 across intron 4 that increased risk among participants with the TC (OR = 1.31, 95% CI = 1.09-1.57 haplotype compared to participants with the common haplotype, TT. Across RXRA, one haplotype located 3' of the coding sequence (rs748964, rs3118523, increased RCC risk 35% among individuals with the variant haplotype compared to those with the most common haplotype. This study comprehensively evaluated genetic variation across eight vitamin D pathway genes in relation to RCC risk. We found increased risk associated with VDR and RXRA. Replication studies are warranted to confirm these findings.

  1. Genome Analysis of Latin American Cervical Cancer: Frequent Activation of the PIK3CA Pathway.

    Science.gov (United States)

    Lou, Hong; Villagran, Guillermo; Boland, Joseph F; Im, Kate M; Polo, Sarita; Zhou, Weiyin; Odey, Ushie; Juárez-Torres, Eligia; Medina-Martínez, Ingrid; Roman-Basaure, Edgar; Mitchell, Jason; Roberson, David; Sawitzke, Julie; Garland, Lisa; Rodríguez-Herrera, Maria; Wells, David; Troyer, Jennifer; Pinto, Francisco Castillo; Bass, Sara; Zhang, Xijun; Castillo, Miriam; Gold, Bert; Morales, Hesler; Yeager, Meredith; Berumen, Jaime; Alvirez, Enrique; Gharzouzi, Eduardo; Dean, Michael

    2015-12-01

    Cervical cancer is one of the most common causes of cancer mortality for women living in poverty, causing more than 28,000 deaths annually in Latin America and 266,000 worldwide. To better understand the molecular basis of the disease, we ascertained blood and tumor samples from Guatemala and Venezuela and performed genomic characterization. We performed human papillomavirus (HPV) typing and identified somatically mutated genes using exome and ultra-deep targeted sequencing with confirmation in samples from Mexico. Copy number changes were also assessed in the exome sequence. Cervical cancer cases in Guatemala and Venezuela have an average age of diagnosis of 50 years and 5.6 children. Analysis of 675 tumors revealed activation of PIK3CA and other PI3K/AKT pathway genes in 31% of squamous carcinomas and 24% of adeno- and adenosquamous tumors, predominantly at two sites (E542K, E545K) in the helical domain of the PIK3CA gene. This distribution of PIK3CA mutations is distinct from most other cancer types and does not result in the in vitro phosphorylation of AKT. Somatic mutations were more frequent in squamous carcinomas diagnosed after the age of 50 years. Frequent gain of chromosome 3q was found, and low PIK3CA mutation fractions in many tumors suggest that PI3K mutation can be a late event in tumor progression. PI3K pathway mutation is important to cervical carcinogenesis in Latin America. Therapeutic agents that directly target PI3K could play a role in the therapy of this common malignancy. ©2015 American Association for Cancer Research.

  2. Integrative network analysis unveils convergent molecular pathways in Parkinson's disease and diabetes.

    Directory of Open Access Journals (Sweden)

    Jose A Santiago

    Full Text Available Shared dysregulated pathways may contribute to Parkinson's disease and type 2 diabetes, chronic diseases that afflict millions of people worldwide. Despite the evidence provided by epidemiological and gene profiling studies, the molecular and functional networks implicated in both diseases, have not been fully explored. In this study, we used an integrated network approach to investigate the extent to which Parkinson's disease and type 2 diabetes are linked at the molecular level.Using a random walk algorithm within the human functional linkage network we identified a molecular cluster of 478 neighboring genes closely associated with confirmed Parkinson's disease and type 2 diabetes genes. Biological and functional analysis identified the protein serine-threonine kinase activity, MAPK cascade, activation of the immune response, and insulin receptor and lipid signaling as convergent pathways. Integration of results from microarrays studies identified a blood signature comprising seven genes whose expression is dysregulated in Parkinson's disease and type 2 diabetes. Among this group of genes, is the amyloid precursor protein (APP, previously associated with neurodegeneration and insulin regulation. Quantification of RNA from whole blood of 192 samples from two independent clinical trials, the Harvard Biomarker Study (HBS and the Prognostic Biomarker Study (PROBE, revealed that expression of APP is significantly upregulated in Parkinson's disease patients compared to healthy controls. Assessment of biomarker performance revealed that expression of APP could distinguish Parkinson's disease from healthy individuals with a diagnostic accuracy of 80% in both cohorts of patients.These results provide the first evidence that Parkinson's disease and diabetes are strongly linked at the molecular level and that shared molecular networks provide an additional source for identifying highly sensitive biomarkers. Further, these results suggest for the first

  3. Preliminary hazard analysis using sequence tree method

    International Nuclear Information System (INIS)

    Huang Huiwen; Shih Chunkuan; Hung Hungchih; Chen Minghuei; Yih Swu; Lin Jiinming

    2007-01-01

    A system level PHA using sequence tree method was developed to perform Safety Related digital I and C system SSA. The conventional PHA is a brainstorming session among experts on various portions of the system to identify hazards through discussions. However, this conventional PHA is not a systematic technique, the analysis results strongly depend on the experts' subjective opinions. The analysis quality cannot be appropriately controlled. Thereby, this research developed a system level sequence tree based PHA, which can clarify the relationship among the major digital I and C systems. Two major phases are included in this sequence tree based technique. The first phase uses a table to analyze each event in SAR Chapter 15 for a specific safety related I and C system, such as RPS. The second phase uses sequence tree to recognize what I and C systems are involved in the event, how the safety related systems work, and how the backup systems can be activated to mitigate the consequence if the primary safety systems fail. In the sequence tree, the defense-in-depth echelons, including Control echelon, Reactor trip echelon, ESFAS echelon, and Indication and display echelon, are arranged to construct the sequence tree structure. All the related I and C systems, include digital system and the analog back-up systems are allocated in their specific echelon. By this system centric sequence tree based analysis, not only preliminary hazard can be identified systematically, the vulnerability of the nuclear power plant can also be recognized. Therefore, an effective simplified D3 evaluation can be performed as well. (author)

  4. CARBON SEQUESTRATION: A METHODS COMPARATIVE ANALYSIS

    International Nuclear Information System (INIS)

    Christopher J. Koroneos; Dimitrios C. Rovas

    2008-01-01

    All human activities are related with the energy consumption. Energy requirements will continue to rise, due to the modern life and the developing countries growth. Most of the energy demand emanates from fossil fuels. Fossil fuels combustion has negative environmental impacts, with the CO 2 production to be dominating. The fulfillment of the Kyoto protocol criteria requires the minimization of CO 2 emissions. Thus the management of the CO 2 emissions is an urgent matter. The use of appliances with low energy use and the adoption of an energy policy that prevents the unnecessary energy use, can play lead to the reduction of carbon emissions. A different route is the introduction of ''clean'' energy sources, such as renewable energy sources. Last but not least, the development of carbon sequestration methods can be promising technique with big future potential. The objective of this work is the analysis and comparison of different carbon sequestration and deposit methods. Ocean deposit, land ecosystems deposit, geological formations deposit and radical biological and chemical approaches will be analyzed

  5. A bias-reducing pathway enrichment analysis of genome-wide association data confirmed association of the MHC region with schizophrenia.

    LENUS (Irish Health Repository)

    Jia, Peilin

    2012-02-01

    After the recent successes of genome-wide association studies (GWAS), one key challenge is to identify genetic variants that might have a significant joint effect on complex diseases but have failed to be identified individually due to weak to moderate marginal effect. One popular and effective approach is gene set based analysis, which investigates the joint effect of multiple functionally related genes (eg, pathways). However, a typical gene set analysis method is biased towards long genes, a problem that is especially severe in psychiatric diseases.

  6. Pathways of economic inequalities in maternal and child health in urban India: a decomposition analysis.

    Directory of Open Access Journals (Sweden)

    Srinivas Goli

    Full Text Available BACKGROUND/OBJECTIVE: Children and women comprise vulnerable populations in terms of health and are gravely affected by the impact of economic inequalities through multi-dimensional channels. Urban areas are believed to have better socioeconomic and maternal and child health indicators than rural areas. This perception leads to the implementation of health policies ignorant of intra-urban health inequalities. Therefore, the objective of this study is to explain the pathways of economic inequalities in maternal and child health indicators among the urban population of India. METHODS: Using data from the third wave of the National Family Health Survey (NFHS, 2005-06, this study calculated relative contribution of socioeconomic factors to inequalities in key maternal and child health indicators such as antenatal check-ups (ANCs, institutional deliveries, proportion of children with complete immunization, proportion of underweight children, and Infant Mortality Rate (IMR. Along with regular CI estimates, this study applied widely used regression-based Inequality Decomposition model proposed by Wagstaff and colleagues. RESULTS: The CI estimates show considerable economic inequalities in women with less than 3 ANCs (CI = -0.3501, institutional delivery (CI = -0.3214, children without fully immunization (CI = -0.18340, underweight children (CI = -0.19420, and infant deaths (CI = -0.15596. Results of the decomposition model reveal that illiteracy among women and her partner, poor economic status, and mass media exposure are the critical factors contributing to economic inequalities in maternal and child health indicators. The residuals in all the decomposition models are very less; this implies that the above mentioned factors explained maximum inequalities in maternal and child health of urban population in India. CONCLUSION: Findings suggest that illiteracy among women and her partner, poor economic status, and mass media exposure are the critical

  7. Recent improvement of the resonance analysis methods

    International Nuclear Information System (INIS)

    Sirakov, I.; Lukyanov, A.

    2000-01-01

    By the use of a two-step method called Combined, the R-matrix Wigner-Eisenbud representation in the resonance reaction theory has been converted into other equivalent representations (parameterizations) of the collision matrix with Poles in E domain. Two of them called Capture Elimination (CE) and Reaction Elimination (RE) representation respectively, have energy independent parameters and are both rigorous and applicable. The CE representation is essentially a generalization of the Reich-Moore (RM) formalism. The RE representation, in turn, offers some distinct advantages when analyzing fissile nuclei. The latter does not require any approximation for the capture channels and does not need any assumption about the number of fission channels in contrast to the RM representation. Unlike the RM parameters the RE ones are uniquely determined for applications in the resonance analysis. When given in the RE representation, neutron cross sections of fissile nuclei in the resolved resonance region are presented through simple scalar expressions without the need of matrix inversion. Various computer codes have been developed to demonstrate the viability of the new method. The RM parameters of the fissile nuclei have been converted into equivalent RE parameters implying the RM assumptions (REFINE code). Conversely, the RE parameters have been converted into corresponding RM parameters when one fission channel is present and the RM parameter set is unique, e.g. Pu-239, J =1 (REVERSE code). To further enhance the flexibility of the proposed method the obtained RE parameters have been converted into equivalent Generalized Pole parameters (REFILE code), which are parameters of the rigorous pole expansion of the collision matrix in √E domain. equi valent sets of RM, RE and GP parameters of 239 Pu are given as an example. It has been pointed out that all the advantages of the newly proposed representation can be implemented through an independent evaluation of the RE resonance

  8. Comparative transcriptome analysis on the synthesis pathway of honey bee (Apis mellifera) mandibular gland secretions.

    Science.gov (United States)

    Wu, YuQi; Zheng, HuoQing; Corona, Miguel; Pirk, Christian; Meng, Fei; Zheng, YuFei; Hu, FuLiang

    2017-07-03

    Secretions from mandibular glands (MGs) have important caste-specific functions that are associated with the social evolution of honey bees. To gain insights into the molecular architecture underlying these caste differences, we compared the gene expression patterns of MGs from queens, queenright workers (WQRs) and queenless workers (WQLs) using high-throughput RNA-sequencing technology. In total, we identified 46 candidate genes associated with caste-specific biosynthesis of fatty acid pheromones in the MG, including members of cytochrome P450 (CYP450) family and genes involved in fatty acid β-oxidation and ω-oxidation. For further identification of the CYP450s genes involved in the biosynthesis of MG secretions, we analyzed by means of qPCR, the expression levels of six of the CYP450 genes most abundantly expressed in the transcriptome analysis across different castes, ages, tasks and tissues. Our analysis revealed that CYP6AS8 and CYP6AS11, the most abundantly expressed CYP450 genes in worker and queen MGs, respectively, are selectively expressed in the MGs of workers and queens compared to other tissues. These results suggest that these genes might be responsible for the critical bifurcated hydroxylation process in the biosynthesis pathway. Our study contributes to the description of the molecular basis for the biosynthesis of fatty acid-derived pheromones in the MGs.

  9. Genome-wide association study and biological pathway analysis of the Eimeria maxima response in broilers.

    Science.gov (United States)

    Hamzić, Edin; Buitenhuis, Bart; Hérault, Frédéric; Hawken, Rachel; Abrahamsen, Mitchel S; Servin, Bertrand; Elsen, Jean-Michel; Pinard-van der Laan, Marie-Hélène; Bed'Hom, Bertrand

    2015-11-25

    Coccidiosis is the most common and costly disease in the poultry industry and is caused by protozoans of the Eimeria genus. The current control of coccidiosis, based on the use of anticoccidial drugs and vaccination, faces serious obstacles such as drug resistance and the high costs for the development of efficient vaccines, respectively. Therefore, the current control programs must be expanded with complementary approaches such as the use of genetics to improve the host response to Eimeria infections. Recently, we have performed a large-scale challenge study on Cobb500 broilers using E. maxima for which we investigated variability among animals in response to the challenge. As a follow-up to this challenge study, we performed a genome-wide association study (GWAS) to identify genomic regions underlying variability of the measured traits in the response to Eimeria maxima in broilers. Furthermore, we conducted a post-GWAS functional analysis to increase our biological understanding of the underlying response to Eimeria maxima challenge. In total, we identified 22 single nucleotide polymorphisms (SNPs) with q value Eimeria maxima in broilers. Furthermore, the post-GWAS functional analysis indicates that biological pathways and networks involved in tissue proliferation and repair along with the primary innate immune response may play the most important role during the early stage of Eimeria maxima infection in broilers.

  10. Sensitivity analysis on a dose-calculation model for the terrestrial food-chain pathway

    International Nuclear Information System (INIS)

    Abdel-Aal, M.M.

    1994-01-01

    Parameter uncertainty and sensitivity were applied to the U.S. Regulatory Commission's (NRC) Regulatory Guide 1.109 (1977) models for calculating the ingestion dose via a terrestrial food-chain pathway in order to assess the transport of chronically released, low-level effluents from light-water reactors. In the analysis, we used the generation of latin hypercube samples (LHS) and employed a constrained sampling scheme. The generation of these samples is based on information supplied to the LHS program for variables or parameters. The actually sampled values are used to form vectors of variables that are commonly used as inputs to computer models for the purpose of sensitivity and uncertainty analysis. Regulatory models consider the concentrations of radionuclides that are deposited on plant tissues or lead to root uptake of nuclides initially deposited on soil. We also consider concentrations in milk and beef as a consequence of grazing on contaminated pasture or ingestion of contaminated feed by dairy and beef cattle. The radionuclides Sr-90 and Cs-137 were selected for evaluation. The most sensitive input parameters for the model were the ground-dispersion parameter, release rates of radionuclides, and soil-to-plant transfer coefficients of radionuclides. (Author)

  11. Molecular and Biochemical Analysis of Chalcone Synthase from Freesia hybrid in flavonoid biosynthetic pathway.

    Directory of Open Access Journals (Sweden)

    Wei Sun

    Full Text Available Chalcone synthase (CHS catalyzes the first committed step in the flavonoid biosynthetic pathway. In this study, the cDNA (FhCHS1 encoding CHS from Freesia hybrida was successfully isolated and analyzed. Multiple sequence alignments showed that both the conserved CHS active site residues and CHS signature sequence were found in the deduced amino acid sequence of FhCHS1. Meanwhile, crystallographic analysis revealed that protein structure of FhCHS1 is highly similar to that of alfalfa CHS2, and the biochemical analysis results indicated that it has an enzymatic role in naringenin biosynthesis. Moreover, quantitative real-time PCR was performed to detect the transcript levels of FhCHS1 in flowers and different tissues, and patterns of FhCHS1 expression in flowers showed significant correlation to the accumulation patterns of anthocyanin during flower development. To further characterize the functionality of FhCHS1, its ectopic expression in Arabidopsis thaliana tt4 mutants and Petunia hybrida was performed. The results showed that overexpression of FhCHS1 in tt4 mutants fully restored the pigmentation phenotype of the seed coats, cotyledons and hypocotyls, while transgenic petunia expressing FhCHS1 showed flower color alteration from white to pink. In summary, these results suggest that FhCHS1 plays an essential role in the biosynthesis of flavonoid in Freesia hybrida and may be used to modify the components of flavonoids in other plants.

  12. A comprehensive association analysis of homocysteine metabolic pathway genes in Singaporean Chinese with ischemic stroke.

    Directory of Open Access Journals (Sweden)

    Hui-Qi Low

    Full Text Available BACKGROUND: The effect of genetic factors, apart from 5,10-methylenetetrahydrofolate reductase (MTHFR polymorphisms, on elevated plasma homocysteine levels and increasing ischemic stroke risk have not been fully elucidated. We conducted a comprehensive analysis of 25 genes involved in homocysteine metabolism to investigate association of common variants within these genes with ischemic stroke risk. METHODOLOGY/PRINCIPAL FINDINGS: The study was done in two stages. In the initial study, SNP and haplotype-based association analyses were performed using 147 tagging Single Nucleotide Polymorphisms (SNPs in 360 stroke patients and 354 non-stroke controls of Singaporean Chinese ethnicity. Joint association analysis of significant SNPs was then performed to assess the cumulative effect of these variants on ischemic stroke risk. In the replication study, 8 SNPs were selected for validation in an independent set of 420 matched case-control pairs of Singaporean Chinese ethnicity. SNP analysis from the initial study suggested 3 risk variants in the MTRR, SHMT1 and TCN2 genes which were moderately associated with ischemic stroke risk, independent of known stroke risk factors. Although the replication study failed to support single-SNP associations observed in the initial study, joint association analysis of the 3 variants in combined initial and replication samples revealed a trend of elevated risk with an increased number of risk alleles (Joint P(trend = 1.2×10(-6. CONCLUSIONS: Our study did not find direct evidence of associations between any single polymorphisms of homocysteine metabolic pathway genes and ischemic stroke, but suggests that the cumulative effect of several small to moderate risk variants from genes involved in homocysteine metabolism may jointly confer a significant impact on ischemic stroke risk.

  13. Well-to-wake analysis of ethanol-to-jet and sugar-to-jet pathways.

    Science.gov (United States)

    Han, Jeongwoo; Tao, Ling; Wang, Michael

    2017-01-01

    To reduce the environmental impacts of the aviation sector as air traffic grows steadily, the aviation industry has paid increasing attention to bio-based alternative jet fuels (AJFs), which may provide lower life-cycle petroleum consumption and greenhouse gas (GHG) emissions than petroleum jet fuel. This study presents well-to-wake (WTWa) results for four emerging AJFs: ethanol-to-jet (ETJ) from corn and corn stover, and sugar-to-jet (STJ) from corn stover via both biological and catalytic conversion. For the ETJ pathways, two plant designs were examined: integrated (processing corn or corn stover as feedstock) and distributed (processing ethanol as feedstock). Also, three H 2 options for STJ via catalytic conversion are investigated: external H 2 from natural gas (NG) steam methane reforming (SMR), in situ H 2 , and H 2 from biomass gasification. Results demonstrate that the feedstock is a key factor in the WTWa GHG emissions of ETJ: corn- and corn stover-based ETJ are estimated to produce WTWa GHG emissions that are 16 and 73%, respectively, less than those of petroleum jet. As for the STJ pathways, this study shows that STJ via biological conversion could generate WTWa GHG emissions 59% below those of petroleum jet. STJ via catalytic conversion could reduce the WTWa GHG emissions by 28% with H 2 from NG SMR or 71% with H 2 from biomass gasification than those of petroleum jet. This study also examines the impacts of co-product handling methods, and shows that the WTWa GHG emissions of corn stover-based ETJ, when estimated with a displacement method, are lower by 11 g CO 2 e/MJ than those estimated with an energy allocation method. Corn- and corn stover-based ETJ as well as corn stover-based STJ show potentials to reduce WTWa GHG emissions compared to petroleum jet. Particularly, WTWa GHG emissions of STJ via catalytic conversion depend highly on the hydrogen source. On the other hand, ETJ offers unique opportunities to exploit extensive existing corn ethanol

  14. Analysis of thermal power calibration method

    International Nuclear Information System (INIS)

    Zagar, T.; Ravnik, M.; Persic, A.

    2000-01-01

    The methods for determining fuel element burnup have recently become interesting because of activities related to the shipment of highly enriched fuel elements back to the United States for final disposal before 2009. The most common and practical method for determining fuel element burnup in research reactors is reactor calculation. Experience has shown that burnup calculations become complicated and biased with uncertainties if a long period of reactor operation must be reproduced. Besides this, accuracy of calculated burnup is always limited with accuracy of reactor power calibration, since burnup calculation is based on calculated power density distribution, which is usually expressed in terms of power released per fuel element and normalised to the reactor power It is obvious that reactor thermal power calibration is very important for precise fuel element burnup calculation. Calculated fuel element burnup is linearly dependent on the thermal reactor power. The reactor power level may be determined from measured absolute thermal flux distribution across the core in the horizontal and vertical planes. Flux distributions are measured with activation of cadmium covered and bare foils irradiated by the steady reactor power. But it should be realised that this method is time consuming and not accurate. This method is practical only for zero power reactors and is in practice very seldom performed for other reactors (e.g. for TRIGA reactor in Ljubljana absolute thermal flux distribution was not performed since reactor reconstruction in 1991). In case of power reactors and research reactors in which a temperature rise across the core is produced and measured than a heat balance method is the most common and accurate method of determining the power output of the core. The purpose of this paper is to analyse the accuracy of calorimetric reactor power calibration method and to analyse the influence of control rod position on nuclear detector reading for TRIGA reactors

  15. Well-to-wheels analysis of hydrogen based fuel-cell vehicle pathways in Shanghai

    International Nuclear Information System (INIS)

    Huang Zhijia; Zhang Xu

    2006-01-01

    Due to high energy efficiency and zero emissions, some believe fuel cell vehicles (FCVs) could revolutionize the automobile industry by replacing internal combustion engine technology, and first boom in China. However, hydrogen infrastructure is one of the major barriers. Because different H 2 pathways have very different energy and emissions effects, the well-to-wheels (WTW) analyses are necessary for adequately evaluating fuel/vehicle systems. The pathways used to supply H 2 for FCVs must be carefully examined by their WTW energy use, greenhouse gases (GHGs) emissions, total criteria pollutions emissions, and urban criteria pollutions emissions. Ten hydrogen pathways in Shanghai have been simulated. The results include well-to-wheels energy use, GHGs emissions, total criteria pollutions and urban criteria pollutions. A fuel-cycle model developed at Argonne National Laboratory-called the Greenhouse gases, Regulated Emissions, and Energy use in Transportation (GREET) model-was used to evaluate well-to-wheels energy and emissions impacts of hydrogen pathways in this study. Because the initial GREET model had no coal and naphtha-based hydrogen pathways, four hydrogen pathway computer programs were added to GREET in the research. To analyze uncertain impacts, commercial software, Crystal Ball(TM) was used to conduct Monte Carlo simulations. Hence, instead of point estimates, the results of this study were probability distributions. Through the research of H 2 pathways in Shanghai, the following conclusions were achieved:(1)All the pathways have significant reductions in WTW petroleum use, except two H 2 pathways from naphtha, which achieve about 20% reductions in WTW petroleum. (2)All the pathways have significant reductions in WTW urban criteria pollutions emissions, except two H 2 pathways from coal, which result in significant increases in WTW urban SO X emissions. (3)The NG-based H 2 pathways have the best WTW energy efficiencies, and the electrolysis H 2 pathways

  16. Gene expression profiling and pathway analysis of human bronchial epithelial cells exposed to airborne particulate matter collected from Saudi Arabia

    International Nuclear Information System (INIS)

    Sun, Hong; Shamy, Magdy; Kluz, Thomas; Muñoz, Alexandra B.; Zhong, Mianhua; Laulicht, Freda; Alghamdi, Mansour A.; Khoder, Mamdouh I.; Chen, Lung-Chi; Costa, Max

    2012-01-01

    Epidemiological studies have established a positive correlation between human mortality and increased concentration of airborne particulate matters (PM). However, the mechanisms underlying PM related human diseases, as well as the molecules and pathways mediating the cellular response to PM, are not fully understood. This study aims to investigate the global gene expression changes in human cells exposed to PM 10 and to identify genes and pathways that may contribute to PM related adverse health effects. Human bronchial epithelial cells were exposed to PM 10 collected from Saudi Arabia for 1 or 4 days, and whole transcript expression was profiled using the GeneChip human gene 1.0 ST array. A total of 140 and 230 genes were identified that significantly changed more than 1.5 fold after PM 10 exposure for 1 or 4 days, respectively. Ingenuity Pathway Analysis revealed that different exposure durations triggered distinct pathways. Genes involved in NRF2-mediated response to oxidative stress were up-regulated after 1 day exposure. In contrast, cells exposed for 4 days exhibited significant changes in genes related to cholesterol and lipid synthesis pathways. These observed changes in cellular oxidative stress and lipid synthesis might contribute to PM related respiratory and cardiovascular disease. -- Highlights: ► PM exposure modulated gene expression and associated pathways in BEAS-2B cells. ► One-day exposure to PM induced genes involved in responding to oxidative stress. ► 4-day exposure to PM changed genes associated to cholesterol and lipid synthesis.

  17. Phase analysis in patients with Wolff-Parkinson-White syndrome. Correlations to surgically confirmed accessory conduction pathways

    Energy Technology Data Exchange (ETDEWEB)

    Nakajima, Kenichi; Bunko, Hisashi; Tada, Akira; Taki, Junichi; Tonami, Norihisa

    1983-09-01

    Twenty-five patients with Wolff-Parkinson-White (WPW) syndrome who underwent surgical division of the accessory conduction pathway (ACP) were studied by gated blood pool studies and phase analyses. All of 11 patients with right cardiac type (R-type) had abnormal initial phase in the right ventricle (RV), while 10 out of 14 patients with left cardiac type (L-type) had initial phase in the left ventricle (LV). However, in 4 L-type patients, there were no significant differences in the initiation of both ventricular contractions. In 10 patients who had radionuclide studies before and after surgical division of the ACP, the ventricular contraction patterns were apparently changed and the abnormal wall motions induced by the presence of ACPs disappeared. These observations indicate that the abnormal initial contraction is associated with pre-excitation of WPW syndrome. Sensitivities to identify the side of preexcitation were 100% (11/11) for R-type and 71% (10/14) for L-type. However, regarding the detection of the precise site of ACP, the agreement was 48% (12/25). Therefore, as a method of preoperative study, it seemed difficult to identify the precise localization of the ACP by phase analysis alone. Phase analysis provided interesting informations and was useful for evaluating patients with WPW syndrome before and after surgery. (author).

  18. Hybrid Methods and Atomistic Models to Explore Free Energies, Rates and Pathways of Protein Shape Changes

    DEFF Research Database (Denmark)

    Wang, Yong

    When I just joined the Lindor-Larsen group as a fresh PhD student, the Nobel Prize in Chemistry that year was awarded for the development of multiscale models for complex chemical systems" to prize the pioneering works of Martin Karplus, Michael Levitt and Arieh Warshel. As a computational......L), whose conformational dynamics however is still not fully understood. We found modern simulation methods and force elds are able to capture key aspects of how this protein changes its shape, paving the way for future studies for systems that are dicult to study experimentally. In Chapter 3, we...... revisited the problem of accurately quantifying the thermodynamics and kinetics, by following a novel route. In this route both of the forward and backward rates are calculated directly from MD simulations using a recently developed enhanced sampling method, called \\infrequent metadynamics...

  19. New methods for clinical pathways-Business Process Modeling Notation (BPMN) and Tangible Business Process Modeling (t.BPM).

    Science.gov (United States)

    Scheuerlein, Hubert; Rauchfuss, Falk; Dittmar, Yves; Molle, Rüdiger; Lehmann, Torsten; Pienkos, Nicole; Settmacher, Utz

    2012-06-01

    Clinical pathways (CP) are nowadays used in numerous institutions, but their real impact is still a matter of debate. The optimal design of a clinical pathway remains unclear and is mainly determined by the expectations of the individual institution. The purpose of the here described pilot project was the development of two CP (colon and rectum carcinoma) according to Business Process Modeling Notation (BPMN) and Tangible Business Process Modeling (t.BPM). BPMN is an established standard for business process modelling in industry and economy. It is, in the broadest sense, a computer programme which enables the description and a relatively easy graphical imaging of complex processes. t.BPM is a modular construction system of the BPMN symbols which enables the creation of an outline or raw model, e.g. by placing the symbols on a spread-out paper sheet. The thus created outline can then be transferred to the computer and further modified as required. CP for the treatment of colon and rectal cancer have been developed with support of an external IT coach. The pathway was developed in an interdisciplinary and interprofessional manner (55 man-days over 15 working days). During this time, necessary interviews with medical, nursing and administrative staffs were conducted as well. Both pathways were developed parallel. Subsequent analysis was focussed on feasibility, expenditure, clarity and suitability for daily clinical practice. The familiarization with BPMN was relatively quick and intuitive. The use of t.BPM enabled the pragmatic, effective and results-directed creation of outlines for the CP. The development of both CP was finished from the diagnostic evaluation to the adjuvant/neoadjuvant therapy and rehabilitation phase. The integration of checklists, guidelines and important medical or other documents is easily accomplished. A direct integration into the hospital computer system is currently not possible for technical reasons. BPMN and t.BPM are sufficiently

  20. BeHealthy Charities Aid Foundation Program, Russia: a Program Impact Pathways (PIP) analysis.

    Science.gov (United States)

    Mukhina, Marina; Novikova, Irina

    2014-09-01

    In 2007, the Charities Aid Foundation Branch in Russia, under the initiative of and with financial support from the Mondelēz International Foundation and Mondelēz International, launched the charitable BeHealthy Program. The program's main focus is the implementation of four interrelated activities: conducting lessons for schoolchildren on healthy nutrition, with an emphasis on breakfast; healthy cooking lessons with children; cultivating nutritional plants; and providing conditions to encourage children to engage in more physical activity. The program serves more than 13,000 children attending public schools in the Leningrad (Lomonosovskii District), Vladimir, and Novgorod regions. BeHealthy provides funding for schools and comprehensive educational materials to help schoolchildren develop habits of healthy nutrition and physical activity, as well as consulting and expert support for school staff and other key stakeholders. The program brings in experts on program implementation and training for teachers. Curriculum support also includes printed and Web-based healthy lifestyle educational materials on best practices and positive experience, as well as meetings and conferences with school representatives and local authorities. One of the biggest challenges for program managers is to fully understand the complexities of the program, and why and how it is expected to induce changes in healthy lifestyle behaviors of the schoolchildren. For more comprehensive understanding, we performed a Program Impact Pathways (PIP) analysis to identify Critical Quality Control Points (CCPs) and a suite of core indicators of the program's impact on healthy lifestyles. The findings were presented at the Healthy Life-styles Program Evaluation Workshop held in Granada, Spain, 13-14 September 2013, under the auspices of the Mondelēz International Foundation. First, we developed an updated logic model based on how the program was executed. We then translated the logic model into a PIP