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Sample records for metabolic flux models

  1. OpenFLUX: efficient modelling software for 13C-based metabolic flux analysis

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    Nielsen Lars K

    2009-05-01

    Full Text Available Abstract Background The quantitative analysis of metabolic fluxes, i.e., in vivo activities of intracellular enzymes and pathways, provides key information on biological systems in systems biology and metabolic engineering. It is based on a comprehensive approach combining (i tracer cultivation on 13C substrates, (ii 13C labelling analysis by mass spectrometry and (iii mathematical modelling for experimental design, data processing, flux calculation and statistics. Whereas the cultivation and the analytical part is fairly advanced, a lack of appropriate modelling software solutions for all modelling aspects in flux studies is limiting the application of metabolic flux analysis. Results We have developed OpenFLUX as a user friendly, yet flexible software application for small and large scale 13C metabolic flux analysis. The application is based on the new Elementary Metabolite Unit (EMU framework, significantly enhancing computation speed for flux calculation. From simple notation of metabolic reaction networks defined in a spreadsheet, the OpenFLUX parser automatically generates MATLAB-readable metabolite and isotopomer balances, thus strongly facilitating model creation. The model can be used to perform experimental design, parameter estimation and sensitivity analysis either using the built-in gradient-based search or Monte Carlo algorithms or in user-defined algorithms. Exemplified for a microbial flux study with 71 reactions, 8 free flux parameters and mass isotopomer distribution of 10 metabolites, OpenFLUX allowed to automatically compile the EMU-based model from an Excel file containing metabolic reactions and carbon transfer mechanisms, showing it's user-friendliness. It reliably reproduced the published data and optimum flux distributions for the network under study were found quickly ( Conclusion We have developed a fast, accurate application to perform steady-state 13C metabolic flux analysis. OpenFLUX will strongly facilitate and

  2. Constraining Genome-Scale Models to Represent the Bow Tie Structure of Metabolism for 13C Metabolic Flux Analysis

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    Tyler W. H. Backman

    2018-01-01

    Full Text Available Determination of internal metabolic fluxes is crucial for fundamental and applied biology because they map how carbon and electrons flow through metabolism to enable cell function. 13 C Metabolic Flux Analysis ( 13 C MFA and Two-Scale 13 C Metabolic Flux Analysis (2S- 13 C MFA are two techniques used to determine such fluxes. Both operate on the simplifying approximation that metabolic flux from peripheral metabolism into central “core” carbon metabolism is minimal, and can be omitted when modeling isotopic labeling in core metabolism. The validity of this “two-scale” or “bow tie” approximation is supported both by the ability to accurately model experimental isotopic labeling data, and by experimentally verified metabolic engineering predictions using these methods. However, the boundaries of core metabolism that satisfy this approximation can vary across species, and across cell culture conditions. Here, we present a set of algorithms that (1 systematically calculate flux bounds for any specified “core” of a genome-scale model so as to satisfy the bow tie approximation and (2 automatically identify an updated set of core reactions that can satisfy this approximation more efficiently. First, we leverage linear programming to simultaneously identify the lowest fluxes from peripheral metabolism into core metabolism compatible with the observed growth rate and extracellular metabolite exchange fluxes. Second, we use Simulated Annealing to identify an updated set of core reactions that allow for a minimum of fluxes into core metabolism to satisfy these experimental constraints. Together, these methods accelerate and automate the identification of a biologically reasonable set of core reactions for use with 13 C MFA or 2S- 13 C MFA, as well as provide for a substantially lower set of flux bounds for fluxes into the core as compared with previous methods. We provide an open source Python implementation of these algorithms at https://github.com/JBEI/limitfluxtocore.

  3. MicrobesFlux: a web platform for drafting metabolic models from the KEGG database

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    Feng Xueyang

    2012-08-01

    Full Text Available Abstract Background Concurrent with the efforts currently underway in mapping microbial genomes using high-throughput sequencing methods, systems biologists are building metabolic models to characterize and predict cell metabolisms. One of the key steps in building a metabolic model is using multiple databases to collect and assemble essential information about genome-annotations and the architecture of the metabolic network for a specific organism. To speed up metabolic model development for a large number of microorganisms, we need a user-friendly platform to construct metabolic networks and to perform constraint-based flux balance analysis based on genome databases and experimental results. Results We have developed a semi-automatic, web-based platform (MicrobesFlux for generating and reconstructing metabolic models for annotated microorganisms. MicrobesFlux is able to automatically download the metabolic network (including enzymatic reactions and metabolites of ~1,200 species from the KEGG database (Kyoto Encyclopedia of Genes and Genomes and then convert it to a metabolic model draft. The platform also provides diverse customized tools, such as gene knockouts and the introduction of heterologous pathways, for users to reconstruct the model network. The reconstructed metabolic network can be formulated to a constraint-based flux model to predict and analyze the carbon fluxes in microbial metabolisms. The simulation results can be exported in the SBML format (The Systems Biology Markup Language. Furthermore, we also demonstrated the platform functionalities by developing an FBA model (including 229 reactions for a recent annotated bioethanol producer, Thermoanaerobacter sp. strain X514, to predict its biomass growth and ethanol production. Conclusion MicrobesFlux is an installation-free and open-source platform that enables biologists without prior programming knowledge to develop metabolic models for annotated microorganisms in the KEGG

  4. Interpreting expression data with metabolic flux models: predicting Mycobacterium tuberculosis mycolic acid production.

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    Caroline Colijn

    2009-08-01

    Full Text Available Metabolism is central to cell physiology, and metabolic disturbances play a role in numerous disease states. Despite its importance, the ability to study metabolism at a global scale using genomic technologies is limited. In principle, complete genome sequences describe the range of metabolic reactions that are possible for an organism, but cannot quantitatively describe the behaviour of these reactions. We present a novel method for modeling metabolic states using whole cell measurements of gene expression. Our method, which we call E-Flux (as a combination of flux and expression, extends the technique of Flux Balance Analysis by modeling maximum flux constraints as a function of measured gene expression. In contrast to previous methods for metabolically interpreting gene expression data, E-Flux utilizes a model of the underlying metabolic network to directly predict changes in metabolic flux capacity. We applied E-Flux to Mycobacterium tuberculosis, the bacterium that causes tuberculosis (TB. Key components of mycobacterial cell walls are mycolic acids which are targets for several first-line TB drugs. We used E-Flux to predict the impact of 75 different drugs, drug combinations, and nutrient conditions on mycolic acid biosynthesis capacity in M. tuberculosis, using a public compendium of over 400 expression arrays. We tested our method using a model of mycolic acid biosynthesis as well as on a genome-scale model of M. tuberculosis metabolism. Our method correctly predicts seven of the eight known fatty acid inhibitors in this compendium and makes accurate predictions regarding the specificity of these compounds for fatty acid biosynthesis. Our method also predicts a number of additional potential modulators of TB mycolic acid biosynthesis. E-Flux thus provides a promising new approach for algorithmically predicting metabolic state from gene expression data.

  5. Genome-scale modeling using flux ratio constraints to enable metabolic engineering of clostridial metabolism in silico.

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    McAnulty, Michael J; Yen, Jiun Y; Freedman, Benjamin G; Senger, Ryan S

    2012-05-14

    Genome-scale metabolic networks and flux models are an effective platform for linking an organism genotype to its phenotype. However, few modeling approaches offer predictive capabilities to evaluate potential metabolic engineering strategies in silico. A new method called "flux balance analysis with flux ratios (FBrAtio)" was developed in this research and applied to a new genome-scale model of Clostridium acetobutylicum ATCC 824 (iCAC490) that contains 707 metabolites and 794 reactions. FBrAtio was used to model wild-type metabolism and metabolically engineered strains of C. acetobutylicum where only flux ratio constraints and thermodynamic reversibility of reactions were required. The FBrAtio approach allowed solutions to be found through standard linear programming. Five flux ratio constraints were required to achieve a qualitative picture of wild-type metabolism for C. acetobutylicum for the production of: (i) acetate, (ii) lactate, (iii) butyrate, (iv) acetone, (v) butanol, (vi) ethanol, (vii) CO2 and (viii) H2. Results of this simulation study coincide with published experimental results and show the knockdown of the acetoacetyl-CoA transferase increases butanol to acetone selectivity, while the simultaneous over-expression of the aldehyde/alcohol dehydrogenase greatly increases ethanol production. FBrAtio is a promising new method for constraining genome-scale models using internal flux ratios. The method was effective for modeling wild-type and engineered strains of C. acetobutylicum.

  6. Deriving metabolic engineering strategies from genome-scale modeling with flux ratio constraints.

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    Yen, Jiun Y; Nazem-Bokaee, Hadi; Freedman, Benjamin G; Athamneh, Ahmad I M; Senger, Ryan S

    2013-05-01

    Optimized production of bio-based fuels and chemicals from microbial cell factories is a central goal of systems metabolic engineering. To achieve this goal, a new computational method of using flux balance analysis with flux ratios (FBrAtio) was further developed in this research and applied to five case studies to evaluate and design metabolic engineering strategies. The approach was implemented using publicly available genome-scale metabolic flux models. Synthetic pathways were added to these models along with flux ratio constraints by FBrAtio to achieve increased (i) cellulose production from Arabidopsis thaliana; (ii) isobutanol production from Saccharomyces cerevisiae; (iii) acetone production from Synechocystis sp. PCC6803; (iv) H2 production from Escherichia coli MG1655; and (v) isopropanol, butanol, and ethanol (IBE) production from engineered Clostridium acetobutylicum. The FBrAtio approach was applied to each case to simulate a metabolic engineering strategy already implemented experimentally, and flux ratios were continually adjusted to find (i) the end-limit of increased production using the existing strategy, (ii) new potential strategies to increase production, and (iii) the impact of these metabolic engineering strategies on product yield and culture growth. The FBrAtio approach has the potential to design "fine-tuned" metabolic engineering strategies in silico that can be implemented directly with available genomic tools. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  7. Flux networks in metabolic graphs

    International Nuclear Information System (INIS)

    Warren, P B; Queiros, S M Duarte; Jones, J L

    2009-01-01

    A metabolic model can be represented as a bipartite graph comprising linked reaction and metabolite nodes. Here it is shown how a network of conserved fluxes can be assigned to the edges of such a graph by combining the reaction fluxes with a conserved metabolite property such as molecular weight. A similar flux network can be constructed by combining the primal and dual solutions to the linear programming problem that typically arises in constraint-based modelling. Such constructions may help with the visualization of flux distributions in complex metabolic networks. The analysis also explains the strong correlation observed between metabolite shadow prices (the dual linear programming variables) and conserved metabolite properties. The methods were applied to recent metabolic models for Escherichia coli, Saccharomyces cerevisiae and Methanosarcina barkeri. Detailed results are reported for E. coli; similar results were found for other organisms

  8. Modelling central metabolic fluxes by constraint-based optimization reveals metabolic reprogramming of developing Solanum lycopersicum (tomato) fruit.

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    Colombié, Sophie; Nazaret, Christine; Bénard, Camille; Biais, Benoît; Mengin, Virginie; Solé, Marion; Fouillen, Laëtitia; Dieuaide-Noubhani, Martine; Mazat, Jean-Pierre; Beauvoit, Bertrand; Gibon, Yves

    2015-01-01

    Modelling of metabolic networks is a powerful tool to analyse the behaviour of developing plant organs, including fruits. Guided by our current understanding of heterotrophic metabolism of plant cells, a medium-scale stoichiometric model, including the balance of co-factors and energy, was constructed in order to describe metabolic shifts that occur through the nine sequential stages of Solanum lycopersicum (tomato) fruit development. The measured concentrations of the main biomass components and the accumulated metabolites in the pericarp, determined at each stage, were fitted in order to calculate, by derivation, the corresponding external fluxes. They were used as constraints to solve the model by minimizing the internal fluxes. The distribution of the calculated fluxes of central metabolism were then analysed and compared with known metabolic behaviours. For instance, the partition of the main metabolic pathways (glycolysis, pentose phosphate pathway, etc.) was relevant throughout fruit development. We also predicted a valid import of carbon and nitrogen by the fruit, as well as a consistent CO2 release. Interestingly, the energetic balance indicates that excess ATP is dissipated just before the onset of ripening, supporting the concept of the climacteric crisis. Finally, the apparent contradiction between calculated fluxes with low values compared with measured enzyme capacities suggest a complex reprogramming of the metabolic machinery during fruit development. With a powerful set of experimental data and an accurate definition of the metabolic system, this work provides important insight into the metabolic and physiological requirements of the developing tomato fruits. © 2014 The Authors The Plant Journal published by Society for Experimental Biology and John Wiley & Sons Ltd.

  9. Constraining genome-scale models to represent the bow tie structure of metabolism for 13C metabolic flux analysis

    DEFF Research Database (Denmark)

    Backman, Tyler W.H.; Ando, David; Singh, Jahnavi

    2018-01-01

    for a minimum of fluxes into core metabolism to satisfy these experimental constraints. Together, these methods accelerate and automate the identification of a biologically reasonable set of core reactions for use with 13C MFA or 2S- 13C MFA, as well as provide for a substantially lower set of flux bounds......Determination of internal metabolic fluxes is crucial for fundamental and applied biology because they map how carbon and electrons flow through metabolism to enable cell function. 13C Metabolic Flux Analysis (13C MFA) and Two-Scale 13C Metabolic Flux Analysis (2S-13C MFA) are two techniques used...

  10. Development of Computational Tools for Metabolic Model Curation, Flux Elucidation and Strain Design

    Energy Technology Data Exchange (ETDEWEB)

    Maranas, Costas D

    2012-05-21

    An overarching goal of the Department of Energy mission is the efficient deployment and engineering of microbial and plant systems to enable biomass conversion in pursuit of high energy density liquid biofuels. This has spurred the pace at which new organisms are sequenced and annotated. This torrent of genomic information has opened the door to understanding metabolism in not just skeletal pathways and a handful of microorganisms but for truly genome-scale reconstructions derived for hundreds of microbes and plants. Understanding and redirecting metabolism is crucial because metabolic fluxes are unique descriptors of cellular physiology that directly assess the current cellular state and quantify the effect of genetic engineering interventions. At the same time, however, trying to keep pace with the rate of genomic data generation has ushered in a number of modeling and computational challenges related to (i) the automated assembly, testing and correction of genome-scale metabolic models, (ii) metabolic flux elucidation using labeled isotopes, and (iii) comprehensive identification of engineering interventions leading to the desired metabolism redirection.

  11. MetaFluxNet: the management of metabolic reaction information and quantitative metabolic flux analysis.

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    Lee, Dong-Yup; Yun, Hongsoek; Park, Sunwon; Lee, Sang Yup

    2003-11-01

    MetaFluxNet is a program package for managing information on the metabolic reaction network and for quantitatively analyzing metabolic fluxes in an interactive and customized way. It allows users to interpret and examine metabolic behavior in response to genetic and/or environmental modifications. As a result, quantitative in silico simulations of metabolic pathways can be carried out to understand the metabolic status and to design the metabolic engineering strategies. The main features of the program include a well-developed model construction environment, user-friendly interface for metabolic flux analysis (MFA), comparative MFA of strains having different genotypes under various environmental conditions, and automated pathway layout creation. http://mbel.kaist.ac.kr/ A manual for MetaFluxNet is available as PDF file.

  12. A Novel Methodology to Estimate Metabolic Flux Distributions in Constraint-Based Models

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    Francesco Alessandro Massucci

    2013-09-01

    Full Text Available Quite generally, constraint-based metabolic flux analysis describes the space of viable flux configurations for a metabolic network as a high-dimensional polytope defined by the linear constraints that enforce the balancing of production and consumption fluxes for each chemical species in the system. In some cases, the complexity of the solution space can be reduced by performing an additional optimization, while in other cases, knowing the range of variability of fluxes over the polytope provides a sufficient characterization of the allowed configurations. There are cases, however, in which the thorough information encoded in the individual distributions of viable fluxes over the polytope is required. Obtaining such distributions is known to be a highly challenging computational task when the dimensionality of the polytope is sufficiently large, and the problem of developing cost-effective ad hoc algorithms has recently seen a major surge of interest. Here, we propose a method that allows us to perform the required computation heuristically in a time scaling linearly with the number of reactions in the network, overcoming some limitations of similar techniques employed in recent years. As a case study, we apply it to the analysis of the human red blood cell metabolic network, whose solution space can be sampled by different exact techniques, like Hit-and-Run Monte Carlo (scaling roughly like the third power of the system size. Remarkably accurate estimates for the true distributions of viable reaction fluxes are obtained, suggesting that, although further improvements are desirable, our method enhances our ability to analyze the space of allowed configurations for large biochemical reaction networks.

  13. Semi-automated curation of metabolic models via flux balance analysis: a case study with Mycoplasma gallisepticum.

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    Eddy J Bautista

    Full Text Available Primarily used for metabolic engineering and synthetic biology, genome-scale metabolic modeling shows tremendous potential as a tool for fundamental research and curation of metabolism. Through a novel integration of flux balance analysis and genetic algorithms, a strategy to curate metabolic networks and facilitate identification of metabolic pathways that may not be directly inferable solely from genome annotation was developed. Specifically, metabolites involved in unknown reactions can be determined, and potentially erroneous pathways can be identified. The procedure developed allows for new fundamental insight into metabolism, as well as acting as a semi-automated curation methodology for genome-scale metabolic modeling. To validate the methodology, a genome-scale metabolic model for the bacterium Mycoplasma gallisepticum was created. Several reactions not predicted by the genome annotation were postulated and validated via the literature. The model predicted an average growth rate of 0.358±0.12[Formula: see text], closely matching the experimentally determined growth rate of M. gallisepticum of 0.244±0.03[Formula: see text]. This work presents a powerful algorithm for facilitating the identification and curation of previously known and new metabolic pathways, as well as presenting the first genome-scale reconstruction of M. gallisepticum.

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

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    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

  15. Uncertainty quantification in flux balance analysis of spatially lumped and distributed models of neuron-astrocyte metabolism.

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    Calvetti, Daniela; Cheng, Yougan; Somersalo, Erkki

    2016-12-01

    Identifying feasible steady state solutions of a brain energy metabolism model is an inverse problem that allows infinitely many solutions. The characterization of the non-uniqueness, or the uncertainty quantification of the flux balance analysis, is tantamount to identifying the degrees of freedom of the solution. The degrees of freedom of multi-compartment mathematical models for energy metabolism of a neuron-astrocyte complex may offer a key to understand the different ways in which the energetic needs of the brain are met. In this paper we study the uncertainty in the solution, using techniques of linear algebra to identify the degrees of freedom in a lumped model, and Markov chain Monte Carlo methods in its extension to a spatially distributed case. The interpretation of the degrees of freedom in metabolic terms, more specifically, glucose and oxygen partitioning, is then leveraged to derive constraints on the free parameters to guarantee that the model is energetically feasible. We demonstrate how the model can be used to estimate the stoichiometric energy needs of the cells as well as the household energy based on the measured oxidative cerebral metabolic rate of glucose and glutamate cycling. Moreover, our analysis shows that in the lumped model the net direction of lactate dehydrogenase (LDH) in the cells can be deduced from the glucose partitioning between the compartments. The extension of the lumped model to a spatially distributed multi-compartment setting that includes diffusion fluxes from capillary to tissue increases the number of degrees of freedom, requiring the use of statistical sampling techniques. The analysis of the distributed model reveals that some of the conclusions valid for the spatially lumped model, e.g., concerning the LDH activity and glucose partitioning, may no longer hold.

  16. 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...

  17. Updates to a 13C metabolic flux analysis model for evaluating energy metabolism in cultured cerebellar granule neurons from neonatal rats.

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    Jekabsons, Mika B; Gebril, Hoda M; Wang, Yan-Hong; Avula, Bharathi; Khan, Ikhlas A

    2017-10-01

    A hexose phosphate recycling model previously developed to infer fluxes through the major glucose consuming pathways in cultured cerebellar granule neurons (CGNs) from neonatal rats metabolizing [1,2- 13 C 2 ]glucose was revised by considering reverse flux through the non-oxidative pentose phosphate pathway (PPP) and symmetrical succinate oxidation within the tricarboxylic acid (TCA) cycle. The model adjusts three flux ratios to effect 13 C distribution in the hexose, pentose, and triose phosphate pools, and in TCA cycle malate to minimize the error between predicted and measured 13 C labeling in exported lactate (i.e., unlabeled, single-, double-, and triple-labeled; M, M1, M2, and M3, respectively). Inclusion of reverse non-oxidative PPP flux substantially increased the number of calculations but ultimately had relatively minor effects on the labeling of glycolytic metabolites. From the error-minimized solution in which the predicted M-M3 lactate differed by 0.49% from that measured by liquid chromatography-triple quadrupole mass spectrometry, the neurons exhibited negligible forward non-oxidative PPP flux. Thus, no glucose was used by the pentose cycle despite explicit consideration of hexose phosphate recycling. Mitochondria consumed only 16% of glucose while 45% was exported as lactate by aerobic glycolysis. The remaining 39% of glucose was shunted to pentose phosphates presumably for de novo nucleotide synthesis, but the proportion metabolized through the oxidative PPP vs. the reverse non-oxidative PPP could not be determined. The lactate exported as M1 (2.5%) and M3 (1.2%) was attributed to malic enzyme, which was responsible for 7.8% of pyruvate production (vs. 92.2% by glycolysis). The updated model is more broadly applicable to different cell types by considering bi-directional flux through the non-oxidative PPP. Its application to cultured neurons utilizing glucose as the sole exogenous substrate has demonstrated substantial oxygen-independent glucose

  18. Synergy between 13C-metabolic flux analysis and flux balance analysis for understanding metabolic adaption to anaerobiosis in e. coli

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    Genome-based Flux Balance Analysis (FBA, constraints based flux analysis) and steady state isotopic-labeling-based Metabolic Flux Analysis (MFA) are complimentary approaches to predicting and measuring the operation and regulation of metabolic networks. Here a genome-derived model of E. coli metabol...

  19. Flux balance analysis of genome-scale metabolic model of rice ...

    Indian Academy of Sciences (India)

    2015-09-28

    Sep 28, 2015 ... biologists are also trying to understand the plant's systems level biochemistry ... metabolism to observe the effect of intracellular transporters' transport ..... [The information about this pathway and associated genes in .... 2013 A method for accounting for mainte- ... Biological control of rice diseases pp 1–11.

  20. A simplified method for power-law modelling of metabolic pathways from time-course data and steady-state flux profiles.

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    Kitayama, Tomoya; Kinoshita, Ayako; Sugimoto, Masahiro; Nakayama, Yoichi; Tomita, Masaru

    2006-07-17

    In order to improve understanding of metabolic systems there have been attempts to construct S-system models from time courses. Conventionally, non-linear curve-fitting algorithms have been used for modelling, because of the non-linear properties of parameter estimation from time series. However, the huge iterative calculations required have hindered the development of large-scale metabolic pathway models. To solve this problem we propose a novel method involving power-law modelling of metabolic pathways from the Jacobian of the targeted system and the steady-state flux profiles by linearization of S-systems. The results of two case studies modelling a straight and a branched pathway, respectively, showed that our method reduced the number of unknown parameters needing to be estimated. The time-courses simulated by conventional kinetic models and those described by our method behaved similarly under a wide range of perturbations of metabolite concentrations. The proposed method reduces calculation complexity and facilitates the construction of large-scale S-system models of metabolic pathways, realizing a practical application of reverse engineering of dynamic simulation models from the Jacobian of the targeted system and steady-state flux profiles.

  1. A simplified method for power-law modelling of metabolic pathways from time-course data and steady-state flux profiles

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    Sugimoto Masahiro

    2006-07-01

    Full Text Available Abstract Background In order to improve understanding of metabolic systems there have been attempts to construct S-system models from time courses. Conventionally, non-linear curve-fitting algorithms have been used for modelling, because of the non-linear properties of parameter estimation from time series. However, the huge iterative calculations required have hindered the development of large-scale metabolic pathway models. To solve this problem we propose a novel method involving power-law modelling of metabolic pathways from the Jacobian of the targeted system and the steady-state flux profiles by linearization of S-systems. Results The results of two case studies modelling a straight and a branched pathway, respectively, showed that our method reduced the number of unknown parameters needing to be estimated. The time-courses simulated by conventional kinetic models and those described by our method behaved similarly under a wide range of perturbations of metabolite concentrations. Conclusion The proposed method reduces calculation complexity and facilitates the construction of large-scale S-system models of metabolic pathways, realizing a practical application of reverse engineering of dynamic simulation models from the Jacobian of the targeted system and steady-state flux profiles.

  2. Metabolic fuels: regulating fluxes to select mix.

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    Weber, Jean-Michel

    2011-01-15

    Animals must regulate the fluxes of multiple fuels to support changing metabolic rates that result from variation in physiological circumstances. The aim of fuel selection strategies is to exploit the advantages of individual substrates while minimizing the impact of disadvantages. All exercising mammals share a general pattern of fuel selection: at the same %V(O(2,max)) they oxidize the same ratio of lipids to carbohydrates. However, highly aerobic species rely more on intramuscular fuels because energy supply from the circulation is constrained by trans-sarcolemmal transfer. Fuel selection is performed by recruiting different muscles, different fibers within the same muscles or different pathways within the same fibers. Electromyographic analyses show that shivering humans can modulate carbohydrate oxidation either through the selective recruitment of type II fibers within the same muscles or by regulating pathway recruitment within type I fibers. The selection patterns of shivering and exercise are different: at the same %V(O(2,max)), a muscle producing only heat (shivering) or significant movement (exercise) strikes a different balance between lipid and carbohydrate oxidation. Long-distance migrants provide an excellent model to characterize how to increase maximal substrate fluxes. High lipid fluxes are achieved through the coordinated upregulation of mobilization, transport and oxidation by activating enzymes, lipid-solubilizing proteins and membrane transporters. These endurance athletes support record lipolytic rates in adipocytes, use lipoprotein shuttles to accelerate transport and show increased capacity for lipid oxidation in muscle mitochondria. Some migrant birds use dietary omega-3 fatty acids as performance-enhancing agents to boost their ability to process lipids. These dietary fatty acids become incorporated in membrane phospholipids and bind to peroxisome proliferator-activated receptors to activate membrane proteins and modify gene expression.

  3. (13)C metabolic flux analysis in neurons utilizing a model that accounts for hexose phosphate recycling within the pentose phosphate pathway.

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    Gebril, Hoda M; Avula, Bharathi; Wang, Yan-Hong; Khan, Ikhlas A; Jekabsons, Mika B

    2016-02-01

    Glycolysis, mitochondrial substrate oxidation, and the pentose phosphate pathway (PPP) are critical for neuronal bioenergetics and oxidation-reduction homeostasis, but quantitating their fluxes remains challenging, especially when processes such as hexose phosphate (i.e., glucose/fructose-6-phosphate) recycling in the PPP are considered. A hexose phosphate recycling model was developed which exploited the rates of glucose consumption, lactate production, and mitochondrial respiration to infer fluxes through the major glucose consuming pathways of adherent cerebellar granule neurons by replicating [(13)C]lactate labeling from metabolism of [1,2-(13)C2]glucose. Flux calculations were predicated on a steady-state system with reactions having known stoichiometries and carbon atom transitions. Non-oxidative PPP activity and consequent hexose phosphate recycling, as well as pyruvate production by cytoplasmic malic enzyme, were optimized by the model and found to account for 28 ± 2% and 7.7 ± 0.2% of hexose phosphate and pyruvate labeling, respectively. From the resulting fluxes, 52 ± 6% of glucose was metabolized by glycolysis, compared to 19 ± 2% by the combined oxidative/non-oxidative pentose cycle that allows for hexose phosphate recycling, and 29 ± 8% by the combined oxidative PPP/de novo nucleotide synthesis reactions. By extension, 62 ± 6% of glucose was converted to pyruvate, the metabolism of which resulted in 16 ± 1% of glucose oxidized by mitochondria and 46 ± 6% exported as lactate. The results indicate a surprisingly high proportion of glucose utilized by the pentose cycle and the reactions synthesizing nucleotides, and exported as lactate. While the in vitro conditions to which the neurons were exposed (high glucose, no lactate or other exogenous substrates) limit extrapolating these results to the in vivo state, the approach provides a means of assessing a number of metabolic fluxes within the context of hexose phosphate recycling in the PPP from a

  4. Non-stationary (13)C-metabolic flux ratio analysis.

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    Hörl, Manuel; Schnidder, Julian; Sauer, Uwe; Zamboni, Nicola

    2013-12-01

    (13)C-metabolic flux analysis ((13)C-MFA) has become a key method for metabolic engineering and systems biology. In the most common methodology, fluxes are calculated by global isotopomer balancing and iterative fitting to stationary (13)C-labeling data. This approach requires a closed carbon balance, long-lasting metabolic steady state, and the detection of (13)C-patterns in a large number of metabolites. These restrictions mostly reduced the application of (13)C-MFA to the central carbon metabolism of well-studied model organisms grown in minimal media with a single carbon source. Here we introduce non-stationary (13)C-metabolic flux ratio analysis as a novel method for (13)C-MFA to allow estimating local, relative fluxes from ultra-short (13)C-labeling experiments and without the need for global isotopomer balancing. The approach relies on the acquisition of non-stationary (13)C-labeling data exclusively for metabolites in the proximity of a node of converging fluxes and a local parameter estimation with a system of ordinary differential equations. We developed a generalized workflow that takes into account reaction types and the availability of mass spectrometric data on molecular ions or fragments for data processing, modeling, parameter and error estimation. We demonstrated the approach by analyzing three key nodes of converging fluxes in central metabolism of Bacillus subtilis. We obtained flux estimates that are in agreement with published results obtained from steady state experiments, but reduced the duration of the necessary (13)C-labeling experiment to less than a minute. These results show that our strategy enables to formally estimate relative pathway fluxes on extremely short time scale, neglecting cellular carbon balancing. Hence this approach paves the road to targeted (13)C-MFA in dynamic systems with multiple carbon sources and towards rich media. © 2013 Wiley Periodicals, Inc.

  5. Metabolic flux analysis of heterotrophic growth in Chlamydomonas reinhardtii.

    Directory of Open Access Journals (Sweden)

    Nanette R Boyle

    Full Text Available Despite the wealth of knowledge available for C. reinhardtii, the central metabolic fluxes of growth on acetate have not yet been determined. In this study, 13C-metabolic flux analysis (13C-MFA was used to determine and quantify the metabolic pathways of primary metabolism in C. reinhardtii cells grown under heterotrophic conditions with acetate as the sole carbon source. Isotopic labeling patterns of compartment specific biomass derived metabolites were used to calculate the fluxes. It was found that acetate is ligated with coenzyme A in the three subcellular compartments (cytosol, mitochondria and plastid included in the model. Two citrate synthases were found to potentially be involved in acetyl-coA metabolism; one localized in the mitochondria and the other acting outside the mitochondria. Labeling patterns demonstrate that Acetyl-coA synthesized in the plastid is directly incorporated in synthesis of fatty acids. Despite having a complete TCA cycle in the mitochondria, it was also found that a majority of the malate flux is shuttled to the cytosol and plastid where it is converted to oxaloacetate providing reducing equivalents to these compartments. When compared to predictions by flux balance analysis, fluxes measured with 13C-MFA were found to be suboptimal with respect to biomass yield; C. reinhardtii sacrifices biomass yield to produce ATP and reducing equivalents.

  6. Prediction of metabolic flux distribution from gene expression data based on the flux minimization principle.

    Directory of Open Access Journals (Sweden)

    Hyun-Seob Song

    Full Text Available Prediction of possible flux distributions in a metabolic network provides detailed phenotypic information that links metabolism to cellular physiology. To estimate metabolic steady-state fluxes, the most common approach is to solve a set of macroscopic mass balance equations subjected to stoichiometric constraints while attempting to optimize an assumed optimal objective function. This assumption is justifiable in specific cases but may be invalid when tested across different conditions, cell populations, or other organisms. With an aim to providing a more consistent and reliable prediction of flux distributions over a wide range of conditions, in this article we propose a framework that uses the flux minimization principle to predict active metabolic pathways from mRNA expression data. The proposed algorithm minimizes a weighted sum of flux magnitudes, while biomass production can be bounded to fit an ample range from very low to very high values according to the analyzed context. We have formulated the flux weights as a function of the corresponding enzyme reaction's gene expression value, enabling the creation of context-specific fluxes based on a generic metabolic network. In case studies of wild-type Saccharomyces cerevisiae, and wild-type and mutant Escherichia coli strains, our method achieved high prediction accuracy, as gauged by correlation coefficients and sums of squared error, with respect to the experimentally measured values. In contrast to other approaches, our method was able to provide quantitative predictions for both model organisms under a variety of conditions. Our approach requires no prior knowledge or assumption of a context-specific metabolic functionality and does not require trial-and-error parameter adjustments. Thus, our framework is of general applicability for modeling the transcription-dependent metabolism of bacteria and yeasts.

  7. Two-Scale 13C Metabolic Flux Analysis for Metabolic Engineering.

    Science.gov (United States)

    Ando, David; Garcia Martin, Hector

    2018-01-01

    Accelerating the Design-Build-Test-Learn (DBTL) cycle in synthetic biology is critical to achieving rapid and facile bioengineering of organisms for the production of, e.g., biofuels and other chemicals. The Learn phase involves using data obtained from the Test phase to inform the next Design phase. As part of the Learn phase, mathematical models of metabolic fluxes give a mechanistic level of comprehension to cellular metabolism, isolating the principle drivers of metabolic behavior from the peripheral ones, and directing future experimental designs and engineering methodologies. Furthermore, the measurement of intracellular metabolic fluxes is specifically noteworthy as providing a rapid and easy-to-understand picture of how carbon and energy flow throughout the cell. Here, we present a detailed guide to performing metabolic flux analysis in the Learn phase of the DBTL cycle, where we show how one can take the isotope labeling data from a 13 C labeling experiment and immediately turn it into a determination of cellular fluxes that points in the direction of genetic engineering strategies that will advance the metabolic engineering process.For our modeling purposes we use the Joint BioEnergy Institute (JBEI) Quantitative Metabolic Modeling (jQMM) library, which provides an open-source, python-based framework for modeling internal metabolic fluxes and making actionable predictions on how to modify cellular metabolism for specific bioengineering goals. It presents a complete toolbox for performing different types of flux analysis such as Flux Balance Analysis, 13 C Metabolic Flux Analysis, and it introduces the capability to use 13 C labeling experimental data to constrain comprehensive genome-scale models through a technique called two-scale 13 C Metabolic Flux Analysis (2S- 13 C MFA) [1]. In addition to several other capabilities, the jQMM is also able to predict the effects of knockouts using the MoMA and ROOM methodologies. The use of the jQMM library is

  8. PFA toolbox: a MATLAB tool for Metabolic Flux Analysis.

    Science.gov (United States)

    Morales, Yeimy; Bosque, Gabriel; Vehí, Josep; Picó, Jesús; Llaneras, Francisco

    2016-07-11

    Metabolic Flux Analysis (MFA) is a methodology that has been successfully applied to estimate metabolic fluxes in living cells. However, traditional frameworks based on this approach have some limitations, particularly when measurements are scarce and imprecise. This is very common in industrial environments. The PFA Toolbox can be used to face those scenarios. Here we present the PFA (Possibilistic Flux Analysis) Toolbox for MATLAB, which simplifies the use of Interval and Possibilistic Metabolic Flux Analysis. The main features of the PFA Toolbox are the following: (a) It provides reliable MFA estimations in scenarios where only a few fluxes can be measured or those available are imprecise. (b) It provides tools to easily plot the results as interval estimates or flux distributions. (c) It is composed of simple functions that MATLAB users can apply in flexible ways. (d) It includes a Graphical User Interface (GUI), which provides a visual representation of the measurements and their uncertainty. (e) It can use stoichiometric models in COBRA format. In addition, the PFA Toolbox includes a User's Guide with a thorough description of its functions and several examples. The PFA Toolbox for MATLAB is a freely available Toolbox that is able to perform Interval and Possibilistic MFA estimations.

  9. Metabolic-flux dependent regulation of microbial physiology.

    Science.gov (United States)

    Litsios, Athanasios; Ortega, Álvaro D; Wit, Ernst C; Heinemann, Matthias

    2018-04-01

    According to the most prevalent notion, changes in cellular physiology primarily occur in response to altered environmental conditions. Yet, recent studies have shown that changes in metabolic fluxes can also trigger phenotypic changes even when environmental conditions are unchanged. This suggests that cells have mechanisms in place to assess the magnitude of metabolic fluxes, that is, the rate of metabolic reactions, and use this information to regulate their physiology. In this review, we describe recent evidence for metabolic flux-sensing and flux-dependent regulation. Furthermore, we discuss how such sensing and regulation can be mechanistically achieved and present a set of new candidates for flux-signaling metabolites. Similar to metabolic-flux sensing, we argue that cells can also sense protein translation flux. Finally, we elaborate on the advantages that flux-based regulation can confer to cells. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  10. Regulation of flux through metabolic cycles

    International Nuclear Information System (INIS)

    Walsh, K.

    1984-01-01

    The branchpoint of the tricarboxylic acid and glyoxylate shunt was characterized in the intact organism by a multidimensional approach. Theory and methodology were developed to determine velocities for the net flow of carbon through the major steps of acetate metabolism in E. coli. Rates were assigned based on the 13 C-NMR spectrum of intracellular glutamate, measured rates of substrate incorporation into end products, the constituent composition of E. coli and a series of conservation equations which described the system at steady state. The in vivo fluxes through the branchpoint of the tricarboxylic acid and glyoxylate cycles were compared to rates calculated from the kinetic constants of the branchpoint enzymes and the intracellular concentrations of their substrates. These studies elucidated the role of isocitrate dehydrogenase phosphorylation in the Krebs cycle and led to the development of a generalized mathematical description of the sensitivity of branchpoints to regulatory control. This theoretical analysis was termed the branchpoint effect and it describes conditions which result in large changes in the flux through an enzyme even though that enzyme is not subject to direct regulatory control. The theoretical and experimental characterization of this system provided a framework to study the effects of enzyme overproduction and underproduction on metabolic processes in the cell. An in vivo method was developed to determine the extent to which an enzyme catalyzes a rate-controlling reaction. The enzyme chosen for this study was citrate synthase

  11. FluxVisualizer, a Software to Visualize Fluxes through Metabolic Networks

    Directory of Open Access Journals (Sweden)

    Tim Daniel Rose

    2018-04-01

    Full Text Available FluxVisualizer (Version 1.0, 2017, freely available at https://fluxvisualizer.ibgc.cnrs.fr is a software to visualize fluxes values on a scalable vector graphic (SVG representation of a metabolic network by colouring or increasing the width of reaction arrows of the SVG file. FluxVisualizer does not aim to draw metabolic networks but to use a customer’s SVG file allowing him to exploit his representation standards with a minimum of constraints. FluxVisualizer is especially suitable for small to medium size metabolic networks, where a visual representation of the fluxes makes sense. The flux distribution can either be an elementary flux mode (EFM, a flux balance analysis (FBA result or any other flux distribution. It allows the automatic visualization of a series of pathways of the same network as is needed for a set of EFMs. The software is coded in python3 and provides a graphical user interface (GUI and an application programming interface (API. All functionalities of the program can be used from the API and the GUI and allows advanced users to add their own functionalities. The software is able to work with various formats of flux distributions (Metatool, CellNetAnalyzer, COPASI and FAME export files as well as with Excel files. This simple software can save a lot of time when evaluating fluxes simulations on a metabolic network.

  12. Effect of amino acid supplementation on titer and glycosylation distribution in hybridoma cell cultures-Systems biology-based interpretation using genome-scale metabolic flux balance model and multivariate data analysis.

    Science.gov (United States)

    Reimonn, Thomas M; Park, Seo-Young; Agarabi, Cyrus D; Brorson, Kurt A; Yoon, Seongkyu

    2016-09-01

    Genome-scale flux balance analysis (FBA) is a powerful systems biology tool to characterize intracellular reaction fluxes during cell cultures. FBA estimates intracellular reaction rates by optimizing an objective function, subject to the constraints of a metabolic model and media uptake/excretion rates. A dynamic extension to FBA, dynamic flux balance analysis (DFBA), can calculate intracellular reaction fluxes as they change during cell cultures. In a previous study by Read et al. (2013), a series of informed amino acid supplementation experiments were performed on twelve parallel murine hybridoma cell cultures, and this data was leveraged for further analysis (Read et al., Biotechnol Prog. 2013;29:745-753). In order to understand the effects of media changes on the model murine hybridoma cell line, a systems biology approach is applied in the current study. Dynamic flux balance analysis was performed using a genome-scale mouse metabolic model, and multivariate data analysis was used for interpretation. The calculated reaction fluxes were examined using partial least squares and partial least squares discriminant analysis. The results indicate media supplementation increases product yield because it raises nutrient levels extending the growth phase, and the increased cell density allows for greater culture performance. At the same time, the directed supplementation does not change the overall metabolism of the cells. This supports the conclusion that product quality, as measured by glycoform assays, remains unchanged because the metabolism remains in a similar state. Additionally, the DFBA shows that metabolic state varies more at the beginning of the culture but less by the middle of the growth phase, possibly due to stress on the cells during inoculation. © 2016 American Institute of Chemical Engineers Biotechnol. Prog., 32:1163-1173, 2016. © 2016 American Institute of Chemical Engineers.

  13. Metabolic cartography: experimental quantification of metabolic fluxes from isotopic labelling studies.

    Science.gov (United States)

    O'Grady, John; Schwender, Jörg; Shachar-Hill, Yair; Morgan, John A

    2012-03-01

    For the past decade, flux maps have provided researchers with an in-depth perspective on plant metabolism. As a rapidly developing field, significant headway has been made recently in computation, experimentation, and overall understanding of metabolic flux analysis. These advances are particularly applicable to the study of plant metabolism. New dynamic computational methods such as non-stationary metabolic flux analysis are finding their place in the toolbox of metabolic engineering, allowing more organisms to be studied and decreasing the time necessary for experimentation, thereby opening new avenues by which to explore the vast diversity of plant metabolism. Also, improved methods of metabolite detection and measurement have been developed, enabling increasingly greater resolution of flux measurements and the analysis of a greater number of the multitude of plant metabolic pathways. Methods to deconvolute organelle-specific metabolism are employed with increasing effectiveness, elucidating the compartmental specificity inherent in plant metabolism. Advances in metabolite measurements have also enabled new types of experiments, such as the calculation of metabolic fluxes based on (13)CO(2) dynamic labelling data, and will continue to direct plant metabolic engineering. Newly calculated metabolic flux maps reveal surprising and useful information about plant metabolism, guiding future genetic engineering of crops to higher yields. Due to the significant level of complexity in plants, these methods in combination with other systems biology measurements are necessary to guide plant metabolic engineering in the future.

  14. Estimation of dynamic flux profiles from metabolic time series data

    Directory of Open Access Journals (Sweden)

    Chou I-Chun

    2012-07-01

    Full Text Available Abstract Background Advances in modern high-throughput techniques of molecular biology have enabled top-down approaches for the estimation of parameter values in metabolic systems, based on time series data. Special among them is the recent method of dynamic flux estimation (DFE, which uses such data not only for parameter estimation but also for the identification of functional forms of the processes governing a metabolic system. DFE furthermore provides diagnostic tools for the evaluation of model validity and of the quality of a model fit beyond residual errors. Unfortunately, DFE works only when the data are more or less complete and the system contains as many independent fluxes as metabolites. These drawbacks may be ameliorated with other types of estimation and information. However, such supplementations incur their own limitations. In particular, assumptions must be made regarding the functional forms of some processes and detailed kinetic information must be available, in addition to the time series data. Results The authors propose here a systematic approach that supplements DFE and overcomes some of its shortcomings. Like DFE, the approach is model-free and requires only minimal assumptions. If sufficient time series data are available, the approach allows the determination of a subset of fluxes that enables the subsequent applicability of DFE to the rest of the flux system. The authors demonstrate the procedure with three artificial pathway systems exhibiting distinct characteristics and with actual data of the trehalose pathway in Saccharomyces cerevisiae. Conclusions The results demonstrate that the proposed method successfully complements DFE under various situations and without a priori assumptions regarding the model representation. The proposed method also permits an examination of whether at all, to what degree, or within what range the available time series data can be validly represented in a particular functional format of

  15. FluxPyt: a Python-based free and open-source software for 13C-metabolic flux analyses.

    Science.gov (United States)

    Desai, Trunil S; Srivastava, Shireesh

    2018-01-01

    13 C-Metabolic flux analysis (MFA) is a powerful approach to estimate intracellular reaction rates which could be used in strain analysis and design. Processing and analysis of labeling data for calculation of fluxes and associated statistics is an essential part of MFA. However, various software currently available for data analysis employ proprietary platforms and thus limit accessibility. We developed FluxPyt, a Python-based truly open-source software package for conducting stationary 13 C-MFA data analysis. The software is based on the efficient elementary metabolite unit framework. The standard deviations in the calculated fluxes are estimated using the Monte-Carlo analysis. FluxPyt also automatically creates flux maps based on a template for visualization of the MFA results. The flux distributions calculated by FluxPyt for two separate models: a small tricarboxylic acid cycle model and a larger Corynebacterium glutamicum model, were found to be in good agreement with those calculated by a previously published software. FluxPyt was tested in Microsoft™ Windows 7 and 10, as well as in Linux Mint 18.2. The availability of a free and open 13 C-MFA software that works in various operating systems will enable more researchers to perform 13 C-MFA and to further modify and develop the package.

  16. Control of fluxes in metabolic networks

    Science.gov (United States)

    Basler, Georg; Nikoloski, Zoran; Larhlimi, Abdelhalim; Barabási, Albert-László; Liu, Yang-Yu

    2016-01-01

    Understanding the control of large-scale metabolic networks is central to biology and medicine. However, existing approaches either require specifying a cellular objective or can only be used for small networks. We introduce new coupling types describing the relations between reaction activities, and develop an efficient computational framework, which does not require any cellular objective for systematic studies of large-scale metabolism. We identify the driver reactions facilitating control of 23 metabolic networks from all kingdoms of life. We find that unicellular organisms require a smaller degree of control than multicellular organisms. Driver reactions are under complex cellular regulation in Escherichia coli, indicating their preeminent role in facilitating cellular control. In human cancer cells, driver reactions play pivotal roles in malignancy and represent potential therapeutic targets. The developed framework helps us gain insights into regulatory principles of diseases and facilitates design of engineering strategies at the interface of gene regulation, signaling, and metabolism. PMID:27197218

  17. A simplified method for power-law modelling of metabolic pathways from time-course data and steady-state flux profiles

    OpenAIRE

    Kitayama, Tomoya; Kinoshita, Ayako; Sugimoto, Masahiro; Nakayama, Yoichi; Tomita, Masaru

    2006-01-01

    Abstract Background In order to improve understanding of metabolic systems there have been attempts to construct S-system models from time courses. Conventionally, non-linear curve-fitting algorithms have been used for modelling, because of the non-linear properties of parameter estimation from time series. However, the huge iterative calculations required have hindered the development of large-scale metabolic pathway models. To solve this problem we propose a novel method involving power-law...

  18. Simple models with ALICE fluxes

    CERN Document Server

    Striet, J

    2000-01-01

    We introduce two simple models which feature an Alice electrodynamics phase. In a well defined sense the Alice flux solutions we obtain in these models obey first order equations similar to those of the Nielsen-Olesen fluxtube in the abelian higgs model in the Bogomol'nyi limit. Some numerical solutions are presented as well.

  19. Modeling Lactococcus lactis using a genome-scale flux model

    Directory of Open Access Journals (Sweden)

    Nielsen Jens

    2005-06-01

    Full Text Available Abstract Background Genome-scale flux models are useful tools to represent and analyze microbial metabolism. In this work we reconstructed the metabolic network of the lactic acid bacteria Lactococcus lactis and developed a genome-scale flux model able to simulate and analyze network capabilities and whole-cell function under aerobic and anaerobic continuous cultures. Flux balance analysis (FBA and minimization of metabolic adjustment (MOMA were used as modeling frameworks. Results The metabolic network was reconstructed using the annotated genome sequence from L. lactis ssp. lactis IL1403 together with physiological and biochemical information. The established network comprised a total of 621 reactions and 509 metabolites, representing the overall metabolism of L. lactis. Experimental data reported in the literature was used to fit the model to phenotypic observations. Regulatory constraints had to be included to simulate certain metabolic features, such as the shift from homo to heterolactic fermentation. A minimal medium for in silico growth was identified, indicating the requirement of four amino acids in addition to a sugar. Remarkably, de novo biosynthesis of four other amino acids was observed even when all amino acids were supplied, which is in good agreement with experimental observations. Additionally, enhanced metabolic engineering strategies for improved diacetyl producing strains were designed. Conclusion The L. lactis metabolic network can now be used for a better understanding of lactococcal metabolic capabilities and potential, for the design of enhanced metabolic engineering strategies and for integration with other types of 'omic' data, to assist in finding new information on cellular organization and function.

  20. Expanded flux variability analysis on metabolic network of Escherichia coli

    Institute of Scientific and Technical Information of China (English)

    CHEN Tong; XIE ZhengWei; OUYANG Qi

    2009-01-01

    Flux balance analysis,based on the mass conservation law in a cellular organism,has been extensively employed to study the interplay between structures and functions of cellular metabolic networks.Consequently,the phenotypes of the metabolism can be well elucidated.In this paper,we introduce the Expanded Flux Variability Analysis (EFVA) to characterize the intrinsic nature of metabolic reactions,such as flexibility,modularity and essentiality,by exploring the trend of the range,the maximum and the minimum flux of reactions.We took the metabolic network of Escherichia coli as an example and analyzed the variability of reaction fluxes under different growth rate constraints.The average variability of all reactions decreases dramatically when the growth rate increases.Consider the noise effect on the metabolic system,we thus argue that the microorganism may practically grow under a suboptimal state.Besides,under the EFVA framework,the reactions are easily to be grouped into catabolic and anabolic groups.And the anabolic groups can be further assigned to specific biomass constitute.We also discovered the growth rate dependent essentiality of reactions.

  1. Co-regulation of metabolic genes is better explained by flux coupling than by network distance.

    Directory of Open Access Journals (Sweden)

    Richard A Notebaart

    2008-01-01

    Full Text Available To what extent can modes of gene regulation be explained by systems-level properties of metabolic networks? Prior studies on co-regulation of metabolic genes have mainly focused on graph-theoretical features of metabolic networks and demonstrated a decreasing level of co-expression with increasing network distance, a naïve, but widely used, topological index. Others have suggested that static graph representations can poorly capture dynamic functional associations, e.g., in the form of dependence of metabolic fluxes across genes in the network. Here, we systematically tested the relative importance of metabolic flux coupling and network position on gene co-regulation, using a genome-scale metabolic model of Escherichia coli. After validating the computational method with empirical data on flux correlations, we confirm that genes coupled by their enzymatic fluxes not only show similar expression patterns, but also share transcriptional regulators and frequently reside in the same operon. In contrast, we demonstrate that network distance per se has relatively minor influence on gene co-regulation. Moreover, the type of flux coupling can explain refined properties of the regulatory network that are ignored by simple graph-theoretical indices. Our results underline the importance of studying functional states of cellular networks to define physiologically relevant associations between genes and should stimulate future developments of novel functional genomic tools.

  2. SUMOFLUX: A Generalized Method for Targeted 13C Metabolic Flux Ratio Analysis

    Science.gov (United States)

    Kogadeeva, Maria

    2016-01-01

    Metabolic fluxes are a cornerstone of cellular physiology that emerge from a complex interplay of enzymes, carriers, and nutrients. The experimental assessment of in vivo intracellular fluxes using stable isotopic tracers is essential if we are to understand metabolic function and regulation. Flux estimation based on 13C or 2H labeling relies on complex simulation and iterative fitting; processes that necessitate a level of expertise that ordinarily preclude the non-expert user. To overcome this, we have developed SUMOFLUX, a methodology that is broadly applicable to the targeted analysis of 13C-metabolic fluxes. By combining surrogate modeling and machine learning, we trained a predictor to specialize in estimating flux ratios from measurable 13C-data. SUMOFLUX targets specific flux features individually, which makes it fast, user-friendly, applicable to experimental design and robust in terms of experimental noise and exchange flux magnitude. Collectively, we predict that SUMOFLUX's properties realistically pave the way to high-throughput flux analyses. PMID:27626798

  3. Pool size measurements facilitate the determination of fluxes at branching points in nonstationary metabolic flux analysis: The case of Arabidopsis thaliana

    Directory of Open Access Journals (Sweden)

    Robert eHeise

    2015-06-01

    Full Text Available Pool size measurements are important for the estimation of absolute intracellular fluxes in particular scenarios based on data from heavy carbon isotope experiments. Recently, steady-state fluxes estimates were obtained for central carbon metabolism in an intact illuminated rosette of Arabidopsis thaliana grown photoautotrophically (Szecowka et al., 2013; Heise et al., 2014. Fluxes were estimated therein by integrating mass-spectrometric data of the dynamics of the unlabeled metabolic fraction, data on metabolic pool sizes, partitioning of metabolic pools between cellular compartments and estimates of photosynthetically inactive pools, with a simplified model of plant central carbon metabolism. However, the fluxes were determined by treating the pool sizes as fixed parameters. Here we investigated whether and, if so, to what extent the treatment of pool sizes as parameters to be optimized in three scenarios may affect the flux estimates. The results are discussed in terms of benchmark values for canonical pathways and reactions, including starch and sucrose synthesis as well as the ribulose-1,5-bisphosphate carboxylation and oxygenation reactions. In addition, we discuss pathways emerging from a divergent branch point for which pool sizes are required for flux estimation, irrespective of the computational approach used for the simulation of the observable labelling pattern. Therefore, our findings indicate the necessity for development of techniques for accurate pool size measurements to improve the quality of flux estimates from nonstationary flux estimates in intact plant cells in the absence of alternative flux measurements.

  4. OptFlux: an open-source software platform for in silico metabolic engineering.

    Science.gov (United States)

    Rocha, Isabel; Maia, Paulo; Evangelista, Pedro; Vilaça, Paulo; Soares, Simão; Pinto, José P; Nielsen, Jens; Patil, Kiran R; Ferreira, Eugénio C; Rocha, Miguel

    2010-04-19

    Over the last few years a number of methods have been proposed for the phenotype simulation of microorganisms under different environmental and genetic conditions. These have been used as the basis to support the discovery of successful genetic modifications of the microbial metabolism to address industrial goals. However, the use of these methods has been restricted to bioinformaticians or other expert researchers. The main aim of this work is, therefore, to provide a user-friendly computational tool for Metabolic Engineering applications. OptFlux is an open-source and modular software aimed at being the reference computational application in the field. It is the first tool to incorporate strain optimization tasks, i.e., the identification of Metabolic Engineering targets, using Evolutionary Algorithms/Simulated Annealing metaheuristics or the previously proposed OptKnock algorithm. It also allows the use of stoichiometric metabolic models for (i) phenotype simulation of both wild-type and mutant organisms, using the methods of Flux Balance Analysis, Minimization of Metabolic Adjustment or Regulatory on/off Minimization of Metabolic flux changes, (ii) Metabolic Flux Analysis, computing the admissible flux space given a set of measured fluxes, and (iii) pathway analysis through the calculation of Elementary Flux Modes. OptFlux also contemplates several methods for model simplification and other pre-processing operations aimed at reducing the search space for optimization algorithms. The software supports importing/exporting to several flat file formats and it is compatible with the SBML standard. OptFlux has a visualization module that allows the analysis of the model structure that is compatible with the layout information of Cell Designer, allowing the superimposition of simulation results with the model graph. The OptFlux software is freely available, together with documentation and other resources, thus bridging the gap from research in strain optimization

  5. Genome-scale modeling for metabolic engineering.

    Science.gov (United States)

    Simeonidis, Evangelos; Price, Nathan D

    2015-03-01

    We focus on the application of constraint-based methodologies and, more specifically, flux balance analysis in the field of metabolic engineering, and enumerate recent developments and successes of the field. We also review computational frameworks that have been developed with the express purpose of automatically selecting optimal gene deletions for achieving improved production of a chemical of interest. The application of flux balance analysis methods in rational metabolic engineering requires a metabolic network reconstruction and a corresponding in silico metabolic model for the microorganism in question. For this reason, we additionally present a brief overview of automated reconstruction techniques. Finally, we emphasize the importance of integrating metabolic networks with regulatory information-an area which we expect will become increasingly important for metabolic engineering-and present recent developments in the field of metabolic and regulatory integration.

  6. Modeling of Zymomonas mobilis central metabolism for novel metabolic engineering strategies.

    Science.gov (United States)

    Kalnenieks, Uldis; Pentjuss, Agris; Rutkis, Reinis; Stalidzans, Egils; Fell, David A

    2014-01-01

    Mathematical modeling of metabolism is essential for rational metabolic engineering. The present work focuses on several types of modeling approach to quantitative understanding of central metabolic network and energetics in the bioethanol-producing bacterium Zymomonas mobilis. Combined use of Flux Balance, Elementary Flux Mode, and thermodynamic analysis of its central metabolism, together with dynamic modeling of the core catabolic pathways, can help to design novel substrate and product pathways by systematically analyzing the solution space for metabolic engineering, and yields insights into the function of metabolic network, hardly achievable without applying modeling tools.

  7. Mathematical modelling of metabolism

    DEFF Research Database (Denmark)

    Gombert, Andreas Karoly; Nielsen, Jens

    2000-01-01

    Mathematical models of the cellular metabolism have a special interest within biotechnology. Many different kinds of commercially important products are derived from the cell factory, and metabolic engineering can be applied to improve existing production processes, as well as to make new processes...... availability of genomic information and powerful analytical techniques, mathematical models also serve as a tool for understanding the cellular metabolism and physiology....... available. Both stoichiometric and kinetic models have been used to investigate the metabolism, which has resulted in defining the optimal fermentation conditions, as well as in directing the genetic changes to be introduced in order to obtain a good producer strain or cell line. With the increasing...

  8. Construction and completion of flux balance models from pathway databases.

    Science.gov (United States)

    Latendresse, Mario; Krummenacker, Markus; Trupp, Miles; Karp, Peter D

    2012-02-01

    Flux balance analysis (FBA) is a well-known technique for genome-scale modeling of metabolic flux. Typically, an FBA formulation requires the accurate specification of four sets: biochemical reactions, biomass metabolites, nutrients and secreted metabolites. The development of FBA models can be time consuming and tedious because of the difficulty in assembling completely accurate descriptions of these sets, and in identifying errors in the composition of these sets. For example, the presence of a single non-producible metabolite in the biomass will make the entire model infeasible. Other difficulties in FBA modeling are that model distributions, and predicted fluxes, can be cryptic and difficult to understand. We present a multiple gap-filling method to accelerate the development of FBA models using a new tool, called MetaFlux, based on mixed integer linear programming (MILP). The method suggests corrections to the sets of reactions, biomass metabolites, nutrients and secretions. The method generates FBA models directly from Pathway/Genome Databases. Thus, FBA models developed in this framework are easily queried and visualized using the Pathway Tools software. Predicted fluxes are more easily comprehended by visualizing them on diagrams of individual metabolic pathways or of metabolic maps. MetaFlux can also remove redundant high-flux loops, solve FBA models once they are generated and model the effects of gene knockouts. MetaFlux has been validated through construction of FBA models for Escherichia coli and Homo sapiens. Pathway Tools with MetaFlux is freely available to academic users, and for a fee to commercial users. Download from: biocyc.org/download.shtml. mario.latendresse@sri.com Supplementary data are available at Bioinformatics online.

  9. Applications of computational modeling in metabolic engineering of yeast

    DEFF Research Database (Denmark)

    Kerkhoven, Eduard J.; Lahtvee, Petri-Jaan; Nielsen, Jens

    2015-01-01

    a preferred flux distribution. These methods point to strategies for altering gene expression; however, fluxes are often controlled by post-transcriptional events. Moreover, GEMs are usually not taking into account metabolic regulation, thermodynamics and enzyme kinetics. To facilitate metabolic engineering......, it is necessary to expand the modeling of metabolism to consider kinetics of individual processes. This review will give an overview about models available for metabolic engineering of yeast and discusses their applications....

  10. Metabolic Flux Analysis of Shewanella spp. Reveals Evolutionary Robustness in Central Carbon Metabolism

    Energy Technology Data Exchange (ETDEWEB)

    Tang, Yinjie J.; Martin, Hector Garcia; Dehal, Paramvir S.; Deutschbauer, Adam; Llora, Xavier; Meadows, Adam; Arkin, Adam; Keasling, Jay D.

    2009-08-19

    Shewanella spp. are a group of facultative anaerobic bacteria widely distributed in marine and fresh-water environments. In this study, we profiled the central metabolic fluxes of eight recently sequenced Shewanella species grown under the same condition in minimal med-ium with [3-13C] lactate. Although the tested Shewanella species had slightly different growth rates (0.23-0.29 h31) and produced different amounts of acetate and pyruvate during early exponential growth (pseudo-steady state), the relative intracellular metabolic flux distributions were remarkably similar. This result indicates that Shewanella species share similar regulation in regard to central carbon metabolic fluxes under steady growth conditions: the maintenance of metabolic robustness is not only evident in a single species under genetic perturbations (Fischer and Sauer, 2005; Nat Genet 37(6):636-640), but also observed through evolutionary related microbial species. This remarkable conservation of relative flux profiles through phylogenetic differences prompts us to introduce the concept of metabotype as an alternative scheme to classify microbial fluxomics. On the other hand, Shewanella spp. display flexibility in the relative flux profiles when switching their metabolism from consuming lactate to consuming pyruvate and acetate.

  11. Maintenance metabolism and carbon fluxes in Bacillus species

    Directory of Open Access Journals (Sweden)

    Decasper Seraina

    2008-06-01

    Full Text Available Abstract Background Selection of an appropriate host organism is crucial for the economic success of biotechnological processes. A generally important selection criterion is a low maintenance energy metabolism to reduce non-productive consumption of substrate. We here investigated, whether various bacilli that are closely related to Bacillus subtilis are potential riboflavin production hosts with low maintenance metabolism. Results While B. subtilis exhibited indeed the highest maintenance energy coefficient, B. licheniformis and B. amyloliquefaciens exhibited only statistically insignificantly reduced maintenance metabolism. Both B. pumilus and B. subtilis (natto exhibited irregular growth patterns under glucose limitation such that the maintenance metabolism could not be determined. The sole exception with significantly reduced maintenance energy requirements was the B. licheniformis strain T380B. The frequently used spo0A mutation significantly increased the maintenance metabolism of B. subtilis. At the level of 13C-detected intracellular fluxes, all investigated bacilli exhibited a significant flux through the pentose phosphate pathway, a prerequisite for efficient riboflavin production. Different from all other species, B. subtilis featured high respiratory tricarboxylic acid cycle fluxes in batch and chemostat cultures. In particular under glucose-limited conditions, this led to significant excess formation of NADPH of B. subtilis, while anabolic consumption was rather balanced with catabolic NADPH formation in the other bacilli. Conclusion Despite its successful commercial production of riboflavin, B. subtilis does not seem to be the optimal cell factory from a bioenergetic point of view. The best choice of the investigated strains is the sporulation-deficient B. licheniformis T380B strain. Beside a low maintenance energy coefficient, this strain grows robustly under different conditions and exhibits only moderate acetate overflow, hence

  12. Linking high-resolution metabolic flux phenotypes and transcriptional regulation in yeast modulated by the global regulator Gcn4p

    DEFF Research Database (Denmark)

    Moxley, Joel F.; Jewett, Michael Christopher; Antoniewicz, Maciek R.

    2009-01-01

    . However, the potential of systems biology approaches is limited by difficulties in integrating metabolic measurements across the functional levels of the cell despite their being most closely linked to cellular phenotype. To address this limitation, we developed a model-based approach to correlate m......RNA and metabolic flux data that combines information from both interaction network models and flux determination models. We started by quantifying 5,764 mRNAs, 54 metabolites, and 83 experimental C-13-based reaction fluxes in continuous cultures of yeast under stress in the absence or presence of global regulator...... of metabolic flux (i.e., use of different reaction pathways) by transcriptional regulation and metabolite interaction density (i.e., level of pairwise metabolite-protein interactions) as a key biosynthetic control determinant. Furthermore, this model predicted flux rewiring in studies of follow...

  13. Multiobjective flux balancing using the NISE method for metabolic network analysis.

    Science.gov (United States)

    Oh, Young-Gyun; Lee, Dong-Yup; Lee, Sang Yup; Park, Sunwon

    2009-01-01

    Flux balance analysis (FBA) is well acknowledged as an analysis tool of metabolic networks in the framework of metabolic engineering. However, FBA has a limitation for solving a multiobjective optimization problem which considers multiple conflicting objectives. In this study, we propose a novel multiobjective flux balance analysis method, which adapts the noninferior set estimation (NISE) method (Solanki et al., 1993) for multiobjective linear programming (MOLP) problems. NISE method can generate an approximation of the Pareto curve for conflicting objectives without redundant iterations of single objective optimization. Furthermore, the flux distributions at each Pareto optimal solution can be obtained for understanding the internal flux changes in the metabolic network. The functionality of this approach is shown by applying it to a genome-scale in silico model of E. coli. Multiple objectives for the poly(3-hydroxybutyrate) [P(3HB)] production are considered simultaneously, and relationships among them are identified. The Pareto curve for maximizing succinic acid production vs. maximizing biomass production is used for the in silico analysis of various combinatorial knockout strains. This proposed method accelerates the strain improvement in the metabolic engineering by reducing computation time of obtaining the Pareto curve and analysis time of flux distribution at each Pareto optimal solution. (c) 2009 American Institute of Chemical Engineers Biotechnol. Prog., 2009.

  14. 13C Metabolic Flux Analysis for systematic metabolic engineering of S. cerevisiae for overproduction of fatty acids.

    Directory of Open Access Journals (Sweden)

    Amit Ghosh

    2016-10-01

    Full Text Available Efficient redirection of microbial metabolism into the abundant production of desired bioproducts remains non-trivial. Here we used flux-based modeling approaches to improve yields of fatty acids in S. cerevisiae. We combined 13C labeling data with comprehensive genome-scale models to shed light onto microbial metabolism and improve metabolic engineering efforts. We concentrated on studying the balance of acetyl-CoA, a precursor metabolite for the biosynthesis of fatty acids. A genome-wide acetyl-CoA balance study showed ATP citrate lyase from Y. lipolytica as a robust source of cytoplasmic acetyl-CoA and malate synthase as a desirable target for down-regulation in terms of acetyl-CoA consumption. These genetic modifications were applied to S. cerevisiae WRY2, a strain that is capable of producing 460 mg L of free fatty acids. With the addition of ATP citrate lyase and down-regulation of malate synthase the engineered strain produced 26 per cent more free fatty acids. Further increases in free fatty acid production of 33 per cent were obtained by knocking out the cytoplasmic glycerol-3-phosphate dehydrogenase, which flux analysis had shown was competing for carbon flux upstream with the carbon flux through the acetyl-CoA production pathway in the cytoplasm. In total, the genetic interventions applied in this work increased fatty acid production by 70 per cent.

  15. Reconstruction and flux analysis of coupling between metabolic pathways of astrocytes and neurons: application to cerebral hypoxia

    Directory of Open Access Journals (Sweden)

    Akιn Ata

    2007-12-01

    Full Text Available Abstract Background It is a daunting task to identify all the metabolic pathways of brain energy metabolism and develop a dynamic simulation environment that will cover a time scale ranging from seconds to hours. To simplify this task and make it more practicable, we undertook stoichiometric modeling of brain energy metabolism with the major aim of including the main interacting pathways in and between astrocytes and neurons. Model The constructed model includes central metabolism (glycolysis, pentose phosphate pathway, TCA cycle, lipid metabolism, reactive oxygen species (ROS detoxification, amino acid metabolism (synthesis and catabolism, the well-known glutamate-glutamine cycle, other coupling reactions between astrocytes and neurons, and neurotransmitter metabolism. This is, to our knowledge, the most comprehensive attempt at stoichiometric modeling of brain metabolism to date in terms of its coverage of a wide range of metabolic pathways. We then attempted to model the basal physiological behaviour and hypoxic behaviour of the brain cells where astrocytes and neurons are tightly coupled. Results The reconstructed stoichiometric reaction model included 217 reactions (184 internal, 33 exchange and 216 metabolites (183 internal, 33 external distributed in and between astrocytes and neurons. Flux balance analysis (FBA techniques were applied to the reconstructed model to elucidate the underlying cellular principles of neuron-astrocyte coupling. Simulation of resting conditions under the constraints of maximization of glutamate/glutamine/GABA cycle fluxes between the two cell types with subsequent minimization of Euclidean norm of fluxes resulted in a flux distribution in accordance with literature-based findings. As a further validation of our model, the effect of oxygen deprivation (hypoxia on fluxes was simulated using an FBA-derivative approach, known as minimization of metabolic adjustment (MOMA. The results show the power of the

  16. 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)

  17. The Protein Cost of Metabolic Fluxes: Prediction from Enzymatic Rate Laws and Cost Minimization.

    Directory of Open Access Journals (Sweden)

    Elad Noor

    2016-11-01

    Full Text Available Bacterial growth depends crucially on metabolic fluxes, which are limited by the cell's capacity to maintain metabolic enzymes. The necessary enzyme amount per unit flux is a major determinant of metabolic strategies both in evolution and bioengineering. It depends on enzyme parameters (such as kcat and KM constants, but also on metabolite concentrations. Moreover, similar amounts of different enzymes might incur different costs for the cell, depending on enzyme-specific properties such as protein size and half-life. Here, we developed enzyme cost minimization (ECM, a scalable method for computing enzyme amounts that support a given metabolic flux at a minimal protein cost. The complex interplay of enzyme and metabolite concentrations, e.g. through thermodynamic driving forces and enzyme saturation, would make it hard to solve this optimization problem directly. By treating enzyme cost as a function of metabolite levels, we formulated ECM as a numerically tractable, convex optimization problem. Its tiered approach allows for building models at different levels of detail, depending on the amount of available data. Validating our method with measured metabolite and protein levels in E. coli central metabolism, we found typical prediction fold errors of 4.1 and 2.6, respectively, for the two kinds of data. This result from the cost-optimized metabolic state is significantly better than randomly sampled metabolite profiles, supporting the hypothesis that enzyme cost is important for the fitness of E. coli. ECM can be used to predict enzyme levels and protein cost in natural and engineered pathways, and could be a valuable computational tool to assist metabolic engineering projects. Furthermore, it establishes a direct connection between protein cost and thermodynamics, and provides a physically plausible and computationally tractable way to include enzyme kinetics into constraint-based metabolic models, where kinetics have usually been ignored or

  18. Surface Flux Modeling for Air Quality Applications

    Directory of Open Access Journals (Sweden)

    Limei Ran

    2011-08-01

    Full Text Available For many gasses and aerosols, dry deposition is an important sink of atmospheric mass. Dry deposition fluxes are also important sources of pollutants to terrestrial and aquatic ecosystems. The surface fluxes of some gases, such as ammonia, mercury, and certain volatile organic compounds, can be upward into the air as well as downward to the surface and therefore should be modeled as bi-directional fluxes. Model parameterizations of dry deposition in air quality models have been represented by simple electrical resistance analogs for almost 30 years. Uncertainties in surface flux modeling in global to mesoscale models are being slowly reduced as more field measurements provide constraints on parameterizations. However, at the same time, more chemical species are being added to surface flux models as air quality models are expanded to include more complex chemistry and are being applied to a wider array of environmental issues. Since surface flux measurements of many of these chemicals are still lacking, resistances are usually parameterized using simple scaling by water or lipid solubility and reactivity. Advances in recent years have included bi-directional flux algorithms that require a shift from pre-computation of deposition velocities to fully integrated surface flux calculations within air quality models. Improved modeling of the stomatal component of chemical surface fluxes has resulted from improved evapotranspiration modeling in land surface models and closer integration between meteorology and air quality models. Satellite-derived land use characterization and vegetation products and indices are improving model representation of spatial and temporal variations in surface flux processes. This review describes the current state of chemical dry deposition modeling, recent progress in bi-directional flux modeling, synergistic model development research with field measurements, and coupling with meteorological land surface models.

  19. To be certain about the uncertainty: Bayesian statistics for 13 C metabolic flux analysis.

    Science.gov (United States)

    Theorell, Axel; Leweke, Samuel; Wiechert, Wolfgang; Nöh, Katharina

    2017-11-01

    13 C Metabolic Fluxes Analysis ( 13 C MFA) remains to be the most powerful approach to determine intracellular metabolic reaction rates. Decisions on strain engineering and experimentation heavily rely upon the certainty with which these fluxes are estimated. For uncertainty quantification, the vast majority of 13 C MFA studies relies on confidence intervals from the paradigm of Frequentist statistics. However, it is well known that the confidence intervals for a given experimental outcome are not uniquely defined. As a result, confidence intervals produced by different methods can be different, but nevertheless equally valid. This is of high relevance to 13 C MFA, since practitioners regularly use three different approximate approaches for calculating confidence intervals. By means of a computational study with a realistic model of the central carbon metabolism of E. coli, we provide strong evidence that confidence intervals used in the field depend strongly on the technique with which they were calculated and, thus, their use leads to misinterpretation of the flux uncertainty. In order to provide a better alternative to confidence intervals in 13 C MFA, we demonstrate that credible intervals from the paradigm of Bayesian statistics give more reliable flux uncertainty quantifications which can be readily computed with high accuracy using Markov chain Monte Carlo. In addition, the widely applied chi-square test, as a means of testing whether the model reproduces the data, is examined closer. © 2017 Wiley Periodicals, Inc.

  20. FAME, the Flux Analysis and Modeling Environment

    Directory of Open Access Journals (Sweden)

    Boele Joost

    2012-01-01

    Full Text Available Abstract Background The creation and modification of genome-scale metabolic models is a task that requires specialized software tools. While these are available, subsequently running or visualizing a model often relies on disjoint code, which adds additional actions to the analysis routine and, in our experience, renders these applications suboptimal for routine use by (systems biologists. Results The Flux Analysis and Modeling Environment (FAME is the first web-based modeling tool that combines the tasks of creating, editing, running, and analyzing/visualizing stoichiometric models into a single program. Analysis results can be automatically superimposed on familiar KEGG-like maps. FAME is written in PHP and uses the Python-based PySCeS-CBM for its linear solving capabilities. It comes with a comprehensive manual and a quick-start tutorial, and can be accessed online at http://f-a-m-e.org/. Conclusions With FAME, we present the community with an open source, user-friendly, web-based "one stop shop" for stoichiometric modeling. We expect the application will be of substantial use to investigators and educators alike.

  1. Flux analysis of central metabolic pathways in Geobactermetallireducens during reduction of solubleFe(III)-NTA

    Energy Technology Data Exchange (ETDEWEB)

    Tang, Yinjie J.; Chakraborty, Romy; Garcia-Martin, Hector; Chu,Jeannie; Hazen, Terry C.; Keasling, Jay D.

    2007-01-01

    We analyzed the carbon fluxes in the central metabolism ofGeobacter metallireducens strain GS-15 using 13C isotopomer modeling.Acetate labeled in the 1st or 2nd position was the sole carbon source,and Fe-NTA was the sole terminal electron acceptor. The measured labeledacetate uptake rate was 21 mmol/gdw/h in the exponential growth phase.The resulting isotope labeling pattern of amino acids allowed an accuratedetermination of the in vivo global metabolic reaction rates (fluxes)through the central metabolic pathways using a computational isotopomermodel. The tracer experiments showed that G. metallireducens containedcomplete biosynthesis pathways for essential metabolism, and this strainmight also have an unusual isoleucine biosynthesis route (usingacetyl-CoA and pyruvate as the precursors). The model indicated that over90 percent of the acetate was completely oxidized to CO2 via a completetricarboxylic acid (TCA) cycle while reducing iron. Pyruvate carboxylaseand phosphoenolpyruvate carboxykinase were present under theseconditions, but enzymes in the glyoxylate shunt and malic enzyme wereabsent. Gluconeogenesis and the pentose phosphate pathway were mainlyemployed for biosynthesis and accounted for less than 3 percent of totalcarbon consumption. The model also indicated surprisingly highreversibility in the reaction between oxoglutarate and succinate. Thisstep operates close to the thermodynamic equilibrium possibly becausesuccinate is synthesized via a transferase reaction, and the conversionof oxoglutarate to succinate is a rate limiting step for carbonmetabolism. These findings enable a better understanding of therelationship between genome annotation and extant metabolic pathways inG. metallireducens.

  2. Applications of computational modeling in metabolic engineering of yeast.

    Science.gov (United States)

    Kerkhoven, Eduard J; Lahtvee, Petri-Jaan; Nielsen, Jens

    2015-02-01

    Generally, a microorganism's phenotype can be described by its pattern of metabolic fluxes. Although fluxes cannot be measured directly, inference of fluxes is well established. In biotechnology the aim is often to increase the capacity of specific fluxes. For this, metabolic engineering methods have been developed and applied extensively. Many of these rely on balancing of intracellular metabolites, redox, and energy fluxes, using genome-scale models (GEMs) that in combination with appropriate objective functions and constraints can be used to predict potential gene targets for obtaining a preferred flux distribution. These methods point to strategies for altering gene expression; however, fluxes are often controlled by post-transcriptional events. Moreover, GEMs are usually not taking into account metabolic regulation, thermodynamics and enzyme kinetics. To facilitate metabolic engineering, tools from synthetic biology have emerged, enabling integration and assembly of naturally nonexistent, but well-characterized components into a living organism. To describe these systems kinetic models are often used and to integrate these systems with the standard metabolic engineering approach, it is necessary to expand the modeling of metabolism to consider kinetics of individual processes. This review will give an overview about models available for metabolic engineering of yeast and discusses their applications. © FEMS 2015. All rights reserved. For permissions, please e-mail: journals.permission@oup.com.

  3. Hydrogen production and metabolic flux analysis of metabolically engineered Escherichia coli strains

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Seohyoung; Seol, Eunhee; Park, Sunghoon [Department of Chemical and Biochemical Engineering, Pusan National University, Busan 609-735 (Korea); Oh, You-Kwan [Bioenergy Research Center, Korea Institute of Energy Research, Daejeon 305-543 (Korea); Wang, G.Y. [Department of Oceanography, University of Hawaii at Manoa Honolulu, HI 96822 (United States)

    2009-09-15

    Escherichia coli can produce H{sub 2} from glucose via formate hydrogen lyase (FHL). In order to improve the H{sub 2} production rate and yield, metabolically engineered E. coli strains, which included pathway alterations in their H{sub 2} production and central carbon metabolism, were developed and characterized by batch experiments and metabolic flux analysis. Deletion of hycA, a negative regulator for FHL, resulted in twofold increase of FHL activity. Deletion of two uptake hydrogenases (1 (hya) and hydrogenase 2 (hyb)) increased H{sub 2} production yield from 1.20 mol/mol glucose to 1.48 mol/mol glucose. Deletion of lactate dehydrogenase (ldhA) and fumarate reductase (frdAB) further improved the H{sub 2} yield; 1.80 mol/mol glucose under high H{sub 2} pressure or 2.11 mol/mol glucose under reduced H{sub 2} pressure. Several batch experiments at varying concentrations of glucose (2.5-10 g/L) and yeast extract (0.3 or 3.0 g/L) were conducted for the strain containing all these genetic alternations, and their carbon and energy balances were analyzed. The metabolic flux analysis revealed that deletion of ldhA and frdAB directed most of the carbons from glucose to the glycolytic pathway leading to H{sub 2} production by FHL, not to the pentose phosphate pathway. (author)

  4. Metabolic flux analysis of the halophilic archaeon Haladaptatus paucihalophilus.

    Science.gov (United States)

    Liu, Guangxiu; Zhang, Manxiao; Mo, Tianlu; He, Lian; Zhang, Wei; Yu, Yi; Zhang, Qi; Ding, Wei

    2015-11-27

    This work reports the (13)C-assisted metabolic flux analysis of Haladaptatus paucihalophilus, a halophilic archaeon possessing an intriguing osmoadaption mechanism. We showed that the carbon flow is through the oxidative tricarboxylic acid (TCA) cycle whereas the reductive TCA cycle is not operative in H. paucihalophilus. In addition, both threonine and the citramalate pathways contribute to isoleucine biosynthesis, whereas lysine is synthesized through the diaminopimelate pathway and not through the α-aminoadipate pathway. Unexpected, the labeling patterns of glycine from the cells grown on [1-(13)C]pyruvate and [2-(13)C]pyruvate suggest that, unlike all the organisms investigated so far, in which glycine is produced exclusively from the serine hydroxymethyltransferase (SHMT) pathway, glycine biosynthesis in H. paucihalophilus involves different pathways including SHMT, threonine aldolase (TA) and the reverse reaction of glycine cleavage system (GCS), demonstrating for the first time that other pathways instead of SHMT can also make a significant contribution to the cellular glycine pool. Transcriptional analysis confirmed that both TA and GCS genes were transcribed in H. paucihalophilus, and the transcriptional level is independent of salt concentrations in the culture media. This study expands our understanding of amino acid biosynthesis and provides valuable insights into the metabolism of halophilic archaea. Copyright © 2015 Elsevier Inc. All rights reserved.

  5. Computational model of cellular metabolic dynamics

    DEFF Research Database (Denmark)

    Li, Yanjun; Solomon, Thomas; Haus, Jacob M

    2010-01-01

    of the cytosol and mitochondria. The model simulated skeletal muscle metabolic responses to insulin corresponding to human hyperinsulinemic-euglycemic clamp studies. Insulin-mediated rate of glucose disposal was the primary model input. For model validation, simulations were compared with experimental data......: intracellular metabolite concentrations and patterns of glucose disposal. Model variations were simulated to investigate three alternative mechanisms to explain insulin enhancements: Model 1 (M.1), simple mass action; M.2, insulin-mediated activation of key metabolic enzymes (i.e., hexokinase, glycogen synthase......, by application of mechanism M.3, the model predicts metabolite concentration changes and glucose partitioning patterns consistent with experimental data. The reaction rate fluxes quantified by this detailed model of insulin/glucose metabolism provide information that can be used to evaluate the development...

  6. Metabolic flux balance analysis and the in silico analysis of Escherichia coli K-12 gene deletions

    Directory of Open Access Journals (Sweden)

    Edwards Jeremy S

    2000-07-01

    Full Text Available Abstract Background Genome sequencing and bioinformatics are producing detailed lists of the molecular components contained in many prokaryotic organisms. From this 'parts catalogue' of a microbial cell, in silico representations of integrated metabolic functions can be constructed and analyzed using flux balance analysis (FBA. FBA is particularly well-suited to study metabolic networks based on genomic, biochemical, and strain specific information. Results Herein, we have utilized FBA to interpret and analyze the metabolic capabilities of Escherichia coli. We have computationally mapped the metabolic capabilities of E. coli using FBA and examined the optimal utilization of the E. coli metabolic pathways as a function of environmental variables. We have used an in silico analysis to identify seven gene products of central metabolism (glycolysis, pentose phosphate pathway, TCA cycle, electron transport system essential for aerobic growth of E. coli on glucose minimal media, and 15 gene products essential for anaerobic growth on glucose minimal media. The in silico tpi-, zwf, and pta- mutant strains were examined in more detail by mapping the capabilities of these in silico isogenic strains. Conclusions We found that computational models of E. coli metabolism based on physicochemical constraints can be used to interpret mutant behavior. These in silica results lead to a further understanding of the complex genotype-phenotype relation. Supplementary information: http://gcrg.ucsd.edu/supplementary_data/DeletionAnalysis/main.htm

  7. 13C Metabolic Flux Analysis for Systematic Metabolic Engineering of S. cerevisiae for Overproduction of Fatty Acids

    DEFF Research Database (Denmark)

    Ghosh, Amit; Ando, David; Gin, Jennifer

    2016-01-01

    Efficient redirection of microbial metabolism into the abundant production of desired bioproducts remains non-trivial. Here, we used flux-based modeling approaches to improve yields of fatty acids in Saccharomyces cerevisiae. We combined 13C labeling data with comprehensive genome-scale models...

  8. Metabolic flux analysis during the exponential growth phase of Saccharomyces cerevisiae in wine fermentations.

    Directory of Open Access Journals (Sweden)

    Manuel Quirós

    Full Text Available As a consequence of the increase in global average temperature, grapes with the adequate phenolic and aromatic maturity tend to be overripe by the time of harvest, resulting in increased sugar concentrations and imbalanced C/N ratios in fermenting musts. This fact sets obvious additional hurdles in the challenge of obtaining wines with reduced alcohols levels, a new trend in consumer demands. It would therefore be interesting to understand Saccharomyces cerevisiae physiology during the fermentation of must with these altered characteristics. The present study aims to determine the distribution of metabolic fluxes during the yeast exponential growth phase, when both carbon and nitrogen sources are in excess, using continuous cultures. Two different sugar concentrations were studied under two different winemaking temperature conditions. Although consumption and production rates for key metabolites were severely affected by the different experimental conditions studied, the general distribution of fluxes in central carbon metabolism was basically conserved in all cases. It was also observed that temperature and sugar concentration exerted a higher effect on the pentose phosphate pathway and glycerol formation than on glycolysis and ethanol production. Additionally, nitrogen uptake, both quantitatively and qualitatively, was strongly influenced by environmental conditions. This work provides the most complete stoichiometric model used for Metabolic Flux Analysis of S. cerevisiae in wine fermentations employed so far, including the synthesis and release of relevant aroma compounds and could be used in the design of optimal nitrogen supplementation of wine fermentations.

  9. Metabolic flux analysis of the halophilic archaeon Haladaptatus paucihalophilus

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Guangxiu; Zhang, Manxiao [Key Laboratory of Desert and Desertification, Cold and Arid Regions Environmental and Engineering Research Institute, Chinese Academy of Sciences, Lanzhou, 730000 (China); Key Laboratory of Extreme Environmental Microbial Resources and Engineering, Gansu Province, Lanzhou, 730000 (China); Mo, Tianlu [Department of Chemistry, Fudan University, Shanghai, 200433 (China); He, Lian [Key Laboratory of Combinatory Biosynthesis and Drug Discovery (Ministry of Education), School of Pharmaceutical Sciences, Wuhan University, Wuhan, 430071 (China); Zhang, Wei [Key Laboratory of Desert and Desertification, Cold and Arid Regions Environmental and Engineering Research Institute, Chinese Academy of Sciences, Lanzhou, 730000 (China); Key Laboratory of Extreme Environmental Microbial Resources and Engineering, Gansu Province, Lanzhou, 730000 (China); Yu, Yi, E-mail: yu_yi@whu.edu.cn [Key Laboratory of Combinatory Biosynthesis and Drug Discovery (Ministry of Education), School of Pharmaceutical Sciences, Wuhan University, Wuhan, 430071 (China); Zhang, Qi, E-mail: qizhang@sioc.ac.cn [Department of Chemistry, Fudan University, Shanghai, 200433 (China); Ding, Wei, E-mail: dingw@lzu.edu.cn [Key Laboratory of Desert and Desertification, Cold and Arid Regions Environmental and Engineering Research Institute, Chinese Academy of Sciences, Lanzhou, 730000 (China); Key Laboratory of Extreme Environmental Microbial Resources and Engineering, Gansu Province, Lanzhou, 730000 (China); Department of Chemistry, Fudan University, Shanghai, 200433 (China)

    2015-11-27

    This work reports the {sup 13}C-assisted metabolic flux analysis of Haladaptatus paucihalophilus, a halophilic archaeon possessing an intriguing osmoadaption mechanism. We showed that the carbon flow is through the oxidative tricarboxylic acid (TCA) cycle whereas the reductive TCA cycle is not operative in H. paucihalophilus. In addition, both threonine and the citramalate pathways contribute to isoleucine biosynthesis, whereas lysine is synthesized through the diaminopimelate pathway and not through the α-aminoadipate pathway. Unexpected, the labeling patterns of glycine from the cells grown on [1-{sup 13}C]pyruvate and [2-{sup 13}C]pyruvate suggest that, unlike all the organisms investigated so far, in which glycine is produced exclusively from the serine hydroxymethyltransferase (SHMT) pathway, glycine biosynthesis in H. paucihalophilus involves different pathways including SHMT, threonine aldolase (TA) and the reverse reaction of glycine cleavage system (GCS), demonstrating for the first time that other pathways instead of SHMT can also make a significant contribution to the cellular glycine pool. Transcriptional analysis confirmed that both TA and GCS genes were transcribed in H. paucihalophilus, and the transcriptional level is independent of salt concentrations in the culture media. This study expands our understanding of amino acid biosynthesis and provides valuable insights into the metabolism of halophilic archaea. - Highlights: • Serine hydroxymethyltransferase, threonine aldolase, and glycine cleavage system all contribute to the glycine pool of H. paucihalophilus. • Threonine and the citramalate pathways contribute equally to the isoleucine biosynthesis in H. paucihalophilus. • Lysine in H. paucihalophilus is synthesized through the diaminopimelate pathway and not through the α-aminoadipate pathway. • Glycine biosynthesis is likely unrelated to the cell osmoadaption mechanism.

  10. Metabolic flux analysis of the halophilic archaeon Haladaptatus paucihalophilus

    International Nuclear Information System (INIS)

    Liu, Guangxiu; Zhang, Manxiao; Mo, Tianlu; He, Lian; Zhang, Wei; Yu, Yi; Zhang, Qi; Ding, Wei

    2015-01-01

    This work reports the "1"3C-assisted metabolic flux analysis of Haladaptatus paucihalophilus, a halophilic archaeon possessing an intriguing osmoadaption mechanism. We showed that the carbon flow is through the oxidative tricarboxylic acid (TCA) cycle whereas the reductive TCA cycle is not operative in H. paucihalophilus. In addition, both threonine and the citramalate pathways contribute to isoleucine biosynthesis, whereas lysine is synthesized through the diaminopimelate pathway and not through the α-aminoadipate pathway. Unexpected, the labeling patterns of glycine from the cells grown on [1-"1"3C]pyruvate and [2-"1"3C]pyruvate suggest that, unlike all the organisms investigated so far, in which glycine is produced exclusively from the serine hydroxymethyltransferase (SHMT) pathway, glycine biosynthesis in H. paucihalophilus involves different pathways including SHMT, threonine aldolase (TA) and the reverse reaction of glycine cleavage system (GCS), demonstrating for the first time that other pathways instead of SHMT can also make a significant contribution to the cellular glycine pool. Transcriptional analysis confirmed that both TA and GCS genes were transcribed in H. paucihalophilus, and the transcriptional level is independent of salt concentrations in the culture media. This study expands our understanding of amino acid biosynthesis and provides valuable insights into the metabolism of halophilic archaea. - Highlights: • Serine hydroxymethyltransferase, threonine aldolase, and glycine cleavage system all contribute to the glycine pool of H. paucihalophilus. • Threonine and the citramalate pathways contribute equally to the isoleucine biosynthesis in H. paucihalophilus. • Lysine in H. paucihalophilus is synthesized through the diaminopimelate pathway and not through the α-aminoadipate pathway. • Glycine biosynthesis is likely unrelated to the cell osmoadaption mechanism.

  11. FILAMENT INTERACTION MODELED BY FLUX ROPE RECONNECTION

    International Nuclear Information System (INIS)

    Toeroek, T.; Chandra, R.; Pariat, E.; Demoulin, P.; Schmieder, B.; Aulanier, G.; Linton, M. G.; Mandrini, C. H.

    2011-01-01

    Hα observations of solar active region NOAA 10501 on 2003 November 20 revealed a very uncommon dynamic process: during the development of a nearby flare, two adjacent elongated filaments approached each other, merged at their middle sections, and separated again, thereby forming stable configurations with new footpoint connections. The observed dynamic pattern is indicative of 'slingshot' reconnection between two magnetic flux ropes. We test this scenario by means of a three-dimensional zero β magnetohydrodynamic simulation, using a modified version of the coronal flux rope model by Titov and Demoulin as the initial condition for the magnetic field. To this end, a configuration is constructed that contains two flux ropes which are oriented side-by-side and are embedded in an ambient potential field. The choice of the magnetic orientation of the flux ropes and of the topology of the potential field is guided by the observations. Quasi-static boundary flows are then imposed to bring the middle sections of the flux ropes into contact. After sufficient driving, the ropes reconnect and two new flux ropes are formed, which now connect the former adjacent flux rope footpoints of opposite polarity. The corresponding evolution of filament material is modeled by calculating the positions of field line dips at all times. The dips follow the morphological evolution of the flux ropes, in qualitative agreement with the observed filaments.

  12. Modelling drug flux through microporated skin.

    Science.gov (United States)

    Rzhevskiy, Alexey S; Guy, Richard H; Anissimov, Yuri G

    2016-11-10

    A simple mathematical equation has been developed to predict drug flux through microporated skin. The theoretical model is based on an approach applied previously to water evaporation through leaf stomata. Pore density, pore radius and drug molecular weight are key model parameters. The predictions of the model were compared with results derived from a simple, intuitive method using porated area alone to estimate the flux enhancement. It is shown that the new approach predicts significantly higher fluxes than the intuitive analysis, with transport being proportional to the total pore perimeter rather than area as intuitively anticipated. Predicted fluxes were in good general agreement with experimental data on drug delivery from the literature, and were quantitatively closer to the measured values than those derived from the intuitive, area-based approach. Copyright © 2016 Elsevier B.V. All rights reserved.

  13. Integrating tracer-based metabolomics data and metabolic fluxes in a linear fashion via Elementary Carbon Modes.

    Science.gov (United States)

    Pey, Jon; Rubio, Angel; Theodoropoulos, Constantinos; Cascante, Marta; Planes, Francisco J

    2012-07-01

    Constraints-based modeling is an emergent area in Systems Biology that includes an increasing set of methods for the analysis of metabolic networks. In order to refine its predictions, the development of novel methods integrating high-throughput experimental data is currently a key challenge in the field. In this paper, we present a novel set of constraints that integrate tracer-based metabolomics data from Isotope Labeling Experiments and metabolic fluxes in a linear fashion. These constraints are based on Elementary Carbon Modes (ECMs), a recently developed concept that generalizes Elementary Flux Modes at the carbon level. To illustrate the effect of our ECMs-based constraints, a Flux Variability Analysis approach was applied to a previously published metabolic network involving the main pathways in the metabolism of glucose. The addition of our ECMs-based constraints substantially reduced the under-determination resulting from a standard application of Flux Variability Analysis, which shows a clear progress over the state of the art. In addition, our approach is adjusted to deal with combinatorial explosion of ECMs in genome-scale metabolic networks. This extension was applied to infer the maximum biosynthetic capacity of non-essential amino acids in human metabolism. Finally, as linearity is the hallmark of our approach, its importance is discussed at a methodological, computational and theoretical level and illustrated with a practical application in the field of Isotope Labeling Experiments. Copyright © 2012 Elsevier Inc. All rights reserved.

  14. Using bioconductor package BiGGR for metabolic flux estimation based on gene expression changes in brain.

    NARCIS (Netherlands)

    Gavai, Anand K.; Supandi, Farahaniza; Hettling, Hannes; Murell, Paul; Leunissen, Jack A.M.; van Beek, Johannes H.G.M.

    2015-01-01

    Predicting the distribution of metabolic fluxes in biochemical networks is of major interest in systems biology. Several databases provide metabolic reconstructions for different organisms. Software to analyze flux distributions exists, among others for the proprietary MATLAB environment. Given the

  15. Using bioconductor package BiGGR for metabolic flux estimation based on gene expression changes in brain

    NARCIS (Netherlands)

    Gavai, A.K.; Supandi, F.; Hettling, H.; Murrell, P.; Leunissen, J.A.M.; Beek, van J.H.G.M.

    2015-01-01

    Predicting the distribution of metabolic fluxes in biochemical networks is of major interest in systems biology. Several databases provide metabolic reconstructions for different organisms. Software to analyze flux distributions exists, among others for the proprietary MATLAB environment. Given the

  16. A model for heliospheric flux-ropes

    Science.gov (United States)

    Nieves-Chinchilla, T.; Linton, M.; Vourlidas, A.; Hidalgo, M. A. U.

    2017-12-01

    This work is presents an analytical flux-rope model, which explores different levels of complexity starting from a circular-cylindrical geometry. The framework of this series of models was established by Nieves-Chinchilla et al. 2016 with the circular-cylindrical analytical flux rope model. The model attempts to describe the magnetic flux rope topology with distorted cross-section as a possible consequence of the interaction with the solar wind. In this model, the flux rope is completely described in a non-orthogonal geometry. The Maxwell equations are solved using tensor calculus consistent with the geometry chosen, invariance along the axial direction, and with the assumption of no radial current density. The model is generalized in terms of the radial and azimuthal dependence of the poloidal current density component and axial current density component. The misalignment between current density and magnetic field is studied in detail for several example profiles of the axial and poloidal current density components. This theoretical analysis provides a map of the force distribution inside of the flux-rope. For reconstruction of the heliospheric flux-ropes, the circular-cylindrical reconstruction technique has been adapted to the new geometry and applied to in situ ICMEs with a flux-rope entrained and tested with cases with clear in situ signatures of distortion. The model adds a piece in the puzzle of the physical-analytical representation of these magnetic structures that should be evaluated with the ultimate goal of reconciling in-situ reconstructions with imaging 3D remote sensing CME reconstructions. Other effects such as axial curvature and/or expansion could be incorporated in the future to fully understand the magnetic structure.

  17. Modeling radon flux from the earth's surface

    International Nuclear Information System (INIS)

    Schery, S.D.; Wasiolek, M.A.

    1998-01-01

    We report development of a 222 Rn flux density model and its use to estimate the 222 Rn flux density over the earth's land surface. The resulting maps are generated on a grid spacing of 1 0 x 1 0 using as input global data for soil radium, soil moisture, and surface temperature. While only a first approximation, the maps suggest a significant regional variation (a factor of three is not uncommon) and a significant seasonal variation (a factor of two is not uncommon) in 222 Rn flux density over the earth's surface. The estimated average global flux density from ice-free land is 34 ± 9 mBq m -2 s -1 . (author)

  18. Chesapeake Bay Sediment Flux Model

    Science.gov (United States)

    1993-06-01

    1988; Van der Molen , -88- 1991; Yoshida, 1981.) The model developed below is based on both of these approaches. It incorporates the diagenetic...288: pp. 289-333. Van der Molen , D.T. (1991): A simple, dynamic model for the simulation of the release of phosphorus from sediments in shallow...1974; Berner, 1980; van Cappellen and Berner, 1988). These relate the diagenetic production of phosphate to the resulting pore water concentration

  19. Nutrient fluxes and net metabolism in a coastal lagoon SW peninsula of Baja California, Mexico

    Directory of Open Access Journals (Sweden)

    Cervantes Duarte, R.

    2016-09-01

    Full Text Available Fluxes of nutrients and net metabolism were estimated in coastal lagoon Magdalena Bay using LOICZ biogeochemical model. In situ data were obtained from 14 sites in the lagoon and also from a fixed site in the adjacent ocean area. Intense upwelling (February to July and faint upwelling (August to January were analyzed from monthly time series. The Temperature, nitrite + nitrate, ammonium and phosphate within the lagoon showed significant differences (p<0.05 between the two periods. Salinity (p=0.408 was more homogeneous (no significantly different due to mixing processes. During the intense upwelling period, nutrients increased in and out of the lagoon due to the influence of Transitional Water and Subartic Water transported by the California Current. However, during the faint upwelling, from August to January, the Transition Water and Subtropical Surface Water were predominant. Magdalena Bay showed denitrification processes of throughout the year as it occurred in other semi-arid coastal lagoons. It also showed a net autotrophic metabolism during intense upwelling and heterotrophic metabolism during faint upwelling. Understanding nutrient flows and net metabolism through simple biogeochemical models can provide tools for better management of the coastal zone.

  20. Flux Balance Analysis of Cyanobacterial Metabolism.The Metabolic Network of Synechocystis sp. PCC 6803

    Czech Academy of Sciences Publication Activity Database

    Knoop, H.; Gründel, M.; Zilliges, Y.; Lehmann, R.; Hoffmann, S.; Lockau, W.; Steuer, Ralf

    2013-01-01

    Roč. 9, č. 6 (2013), e1003081-e1003081 ISSN 1553-7358 R&D Projects: GA MŠk(CZ) EE2.3.20.0256 Institutional support: RVO:67179843 Keywords : SP STRAIN PCC-6803 * SP ATCC 51142 * photoautotrophic metabolism * anacystis-nidulans * reconstructions * pathway * plants * models * growth Subject RIV: EI - Biotechnology ; Bionics Impact factor: 4.829, year: 2013

  1. Carbon conversion efficiency and central metabolic fluxes in developing sunflower (Helianthus annuus L.) embryos.

    Science.gov (United States)

    Alonso, Ana P; Goffman, Fernando D; Ohlrogge, John B; Shachar-Hill, Yair

    2007-10-01

    The efficiency with which developing sunflower embryos convert substrates into seed storage reserves was determined by labeling embryos with [U-(14)C6]glucose or [U-(14)C5]glutamine and measuring their conversion to CO2, oil, protein and other biomass compounds. The average carbon conversion efficiency was 50%, which contrasts with a value of over 80% previously observed in Brassica napus embryos (Goffman et al., 2005), in which light and the RuBisCO bypass pathway allow more efficient conversion of hexose to oil. Labeling levels after incubating sunflower embryos with [U-(14)C4]malate indicated that some carbon from malate enters the plastidic compartment and contributes to oil synthesis. To test this and to map the underlying pattern of metabolic fluxes, separate experiments were carried out in which embryos were labeled to isotopic steady state using [1-(13)C1]glucose, [2-(13)C1]glucose, or [U-(13)C5]glutamine. The resultant labeling in sugars, starch, fatty acids and amino acids was analyzed by NMR and GC-MS. The fluxes through intermediary metabolism were then quantified by computer-aided modeling. The resulting flux map accounted well for the labeling data, was in good agreement with the observed carbon efficiency, and was further validated by testing for agreement with gas exchange measurements. The map shows that the influx of malate into oil is low and that flux through futile cycles (wasting ATP) is low, which contrasts with the high rates previously determined for growing root tips and heterotrophic cell cultures.

  2. Invariability of Central Metabolic Flux Distribution in Shewanella oneidensis MR-1 Under Environmental or Genetic Perturbations

    Energy Technology Data Exchange (ETDEWEB)

    Tang, Yinjie; Martin, Hector Garcia; Deutschbauer, Adam; Feng, Xueyang; Huang, Rick; Llora, Xavier; Arkin, Adam; Keasling, Jay D.

    2009-04-21

    An environmentally important bacterium with versatile respiration, Shewanella oneidensis MR-1, displayed significantly different growth rates under three culture conditions: minimal medium (doubling time {approx} 3 hrs), salt stressed minimal medium (doubling time {approx} 6 hrs), and minimal medium with amino acid supplementation (doubling time {approx}1.5 hrs). {sup 13}C-based metabolic flux analysis indicated that fluxes of central metabolic reactions remained relatively constant under the three growth conditions, which is in stark contrast to the reported significant changes in the transcript and metabolite profiles under various growth conditions. Furthermore, ten transposon mutants of S. oneidensis MR-1 were randomly chosen from a transposon library and their flux distributions through central metabolic pathways were revealed to be identical, even though such mutational processes altered the secondary metabolism, for example, glycine and C1 (5,10-Me-THF) metabolism.

  3. Quantitative intracellular flux modeling and applications in biotherapeutic development and production using CHO cell cultures.

    Science.gov (United States)

    Huang, Zhuangrong; Lee, Dong-Yup; Yoon, Seongkyu

    2017-12-01

    Chinese hamster ovary (CHO) cells have been widely used for producing many recombinant therapeutic proteins. Constraint-based modeling, such as flux balance analysis (FBA) and metabolic flux analysis (MFA), has been developing rapidly for the quantification of intracellular metabolic flux distribution at a systematic level. Such methods would produce detailed maps of flows through metabolic networks, which contribute significantly to better understanding of metabolism in cells. Although these approaches have been extensively established in microbial systems, their application to mammalian cells is sparse. This review brings together the recent development of constraint-based models and their applications in CHO cells. The further development of constraint-based modeling approaches driven by multi-omics datasets is discussed, and a framework of potential modeling application in cell culture engineering is proposed. Improved cell culture system understanding will enable robust developments in cell line and bioprocess engineering thus accelerating consistent process quality control in biopharmaceutical manufacturing. © 2017 Wiley Periodicals, Inc.

  4. Capturing the essence of a metabolic network: a flux balance analysis approach.

    Science.gov (United States)

    Murabito, Ettore; Simeonidis, Evangelos; Smallbone, Kieran; Swinton, Jonathan

    2009-10-07

    As genome-scale metabolic reconstructions emerge, tools to manage their size and complexity will be increasingly important. Flux balance analysis (FBA) is a constraint-based approach widely used to study the metabolic capabilities of cellular or subcellular systems. FBA problems are highly underdetermined and many different phenotypes can satisfy any set of constraints through which the metabolic system is represented. Two of the main concerns in FBA are exploring the space of solutions for a given metabolic network and finding a specific phenotype which is representative for a given task such as maximal growth rate. Here, we introduce a recursive algorithm suitable for overcoming both of these concerns. The method proposed is able to find the alternate optimal patterns of active reactions of an FBA problem and identify the minimal subnetwork able to perform a specific task as optimally as the whole. Our method represents an alternative to and an extension of other approaches conceived for exploring the space of solutions of an FBA problem. It may also be particularly helpful in defining a scaffold of reactions upon which to build up a dynamic model, when the important pathways of the system have not yet been well-defined.

  5. Modelling radiocesium fluxes in forest ecosystems

    International Nuclear Information System (INIS)

    Shaw, G.; Kliashtorin, A.; Mamikhin, S.; Shcheglov, A.; Rafferty, B.; Dvornik, A.; Zhuchenko, T.; Kuchma, N.

    1996-01-01

    Monitoring of radiocesium inventories and fluxes has been carried out in forest ecosystems in Ukraine, Belarus and Ireland to determine distributions and rates of migration. This information has been used to construct and calibrate mathematical models which are being used to predict the likely longevity of contamination of forests and forest products such as timber following the Chernobyl accident

  6. Models of Flux Tubes from Constrained Relaxation

    Indian Academy of Sciences (India)

    tribpo

    J. Astrophys. Astr. (2000) 21, 299 302. Models of Flux Tubes from Constrained Relaxation. Α. Mangalam* & V. Krishan†, Indian Institute of Astrophysics, Koramangala,. Bangalore 560 034, India. *e mail: mangalam @ iiap. ernet. in. † e mail: vinod@iiap.ernet.in. Abstract. We study the relaxation of a compressible plasma to ...

  7. Modelling of Power Fluxes during Thermal Quenches

    International Nuclear Information System (INIS)

    Konz, C.; Coster, D. P.; Lackner, K.; Pautasso, G.

    2005-01-01

    Plasma disruptions, i. e. the sudden loss of magnetic confinement, are unavoidable, at least occasionally, in present day and future tokamaks. The expected energy fluxes to the plasma facing components (PFCs) during disruptions in ITER lie in the range of tens of GW/m''2 for timescales of about a millisecond. Since high energy fluxes can cause severe damage to the PFCs, their design heavily depends on the spatial and temporal distribution of the energy fluxes during disruptions. We investigate the nature of power fluxes during the thermal quench phase of disruptions by means of numerical simulations with the B2 SOLPS fluid code. Based on an ASDEX Upgrade shot, steady-state pre-disruption equilibria are generated which are then subjected to a simulated thermal quench by artificially enhancing the perpendicular transport in the ion and electron channels. The enhanced transport coefficients flows the Rechester and Rosenbluth model (1978) for ergodic transport in a tokamak with destroyed flux surfaces, i. e. χ, D∼const. xT''5/2 where the constants differ by the square root of the mass ratio for ions and electrons. By varying the steady-state neutral puffing rate we can modify the divertor conditions in terms of plasma temperature and density. Our numerical findings indicate that the disruption characteristics depend on the pre disruptive divertor conditions. We study the timescales and the spatial distribution of the divertor power fluxes. The simulated disruptions show rise and decay timescales in the range observed at ASDEX Upgrade. The decay timescale for the central electron temperature of ∼800 μs is typical for non-ITB disruptions. Varying the divertor conditions we find a distinct transition from a regime with symmetric power fluxes to inboard and outboard divertors to a regime where the bulk of the power flux goes to the outboard divertor. This asymmetry in the divertor peak fluxes for the higher puffing case is accompanied by a time delay between the

  8. FAME, the flux analysis and modelling environment

    NARCIS (Netherlands)

    Boele, J.; Olivier, B.G.; Teusink, B.

    2012-01-01

    Background: The creation and modification of genome-scale metabolic models is a task that requires specialized software tools. While these are available, subsequently running or visualizing a model often relies on disjoint code, which adds additional actions to the analysis routine and, in our

  9. Isotopically nonstationary metabolic flux analysis (INST-MFA) of photosynthesis and photorespiration in plants

    Science.gov (United States)

    Photorespiration is a central component of photosynthesis; however to better understand its role it should be viewed in the context of an integrated metabolic network rather than a series of individual reactions that operate independently. Isotopically nonstationary 13C metabolic flux analysis (INST...

  10. Flux-Enabled Exploration of the Role of Sip1 in galactose yeast metabolism

    DEFF Research Database (Denmark)

    Shymansky, Christopher M.; Wang, George; Baidoo, Edward E. K.

    2017-01-01

    13C metabolic flux analysis (13C MFA) is an important systems biology technique that has been used to investigate microbial metabolism for decades. The heterotrimer Snf1 kinase complex plays a key role in the preference Saccharomyces cerevisiae exhibits for glucose over galactose, a phenomenon kn...

  11. Metabolic engineering tools in model cyanobacteria.

    Science.gov (United States)

    Carroll, Austin L; Case, Anna E; Zhang, Angela; Atsumi, Shota

    2018-03-26

    Developing sustainable routes for producing chemicals and fuels is one of the most important challenges in metabolic engineering. Photoautotrophic hosts are particularly attractive because of their potential to utilize light as an energy source and CO 2 as a carbon substrate through photosynthesis. Cyanobacteria are unicellular organisms capable of photosynthesis and CO 2 fixation. While engineering in heterotrophs, such as Escherichia coli, has result in a plethora of tools for strain development and hosts capable of producing valuable chemicals efficiently, these techniques are not always directly transferable to cyanobacteria. However, recent efforts have led to an increase in the scope and scale of chemicals that cyanobacteria can produce. Adaptations of important metabolic engineering tools have also been optimized to function in photoautotrophic hosts, which include Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-Cas9, 13 C Metabolic Flux Analysis (MFA), and Genome-Scale Modeling (GSM). This review explores innovations in cyanobacterial metabolic engineering, and highlights how photoautotrophic metabolism has shaped their development. Copyright © 2018 International Metabolic Engineering Society. Published by Elsevier Inc. All rights reserved.

  12. Synergizing metabolic flux analysis and nucleotide sugar metabolism to understand the control of glycosylation of recombinant protein in CHO cells

    LENUS (Irish Health Repository)

    Burleigh, Susan C

    2011-10-18

    Abstract Background The glycosylation of recombinant proteins can be altered by a range of parameters including cellular metabolism, metabolic flux and the efficiency of the glycosylation process. We present an experimental set-up that allows determination of these key processes associated with the control of N-linked glycosylation of recombinant proteins. Results Chinese hamster ovary cells (CHO) were cultivated in shake flasks at 0 mM glutamine and displayed a reduced growth rate, glucose metabolism and a slower decrease in pH, when compared to other glutamine-supplemented cultures. The N-linked glycosylation of recombinant human chorionic gonadotrophin (HCG) was also altered under these conditions; the sialylation, fucosylation and antennarity decreased, while the proportion of neutral structures increased. A continuous culture set-up was subsequently used to understand the control of HCG glycosylation in the presence of varied glutamine concentrations; when glycolytic flux was reduced in the absence of glutamine, the glycosylation changes that were observed in shake flask culture were similarly detected. The intracellular content of UDP-GlcNAc was also reduced, which correlated with a decrease in sialylation and antennarity of the N-linked glycans attached to HCG. Conclusions The use of metabolic flux analysis illustrated a case of steady state multiplicity, where use of the same operating conditions at each steady state resulted in altered flux through glycolysis and the TCA cycle. This study clearly demonstrated that the control of glycoprotein microheterogeneity may be examined by use of a continuous culture system, metabolic flux analysis and assay of intracellular nucleotides. This system advances our knowledge of the relationship between metabolic flux and the glycosylation of biotherapeutics in CHO cells and will be of benefit to the bioprocessing industry.

  13. Metabolic control over the oxygen consumption flux in intact skeletal muscle: in silico studies.

    Science.gov (United States)

    Liguzinski, Piotr; Korzeniewski, Bernard

    2006-12-01

    It has been postulated previously that a direct activation of all oxidative phosphorylation complexes in parallel with the activation of ATP usage and substrate dehydrogenation (the so-called each-step activation) is the main mechanism responsible for adjusting the rate of ATP production by mitochondria to the current energy demand during rest-to-work transition in intact skeletal muscle in vivo. The present in silico study, using a computer model of oxidative phosphorylation developed previously, analyzes the impact of the each-step-activation mechanism on the distribution of control (defined within Metabolic Control Analysis) over the oxygen consumption flux among the components of the bioenergetic system in intact oxidative skeletal muscle at different energy demands. It is demonstrated that in the absence of each-step activation, the oxidative phosphorylation complexes take over from ATP usage most of the control over the respiration rate and oxidative ATP production at higher (but still physiological) energy demands. This leads to a saturation of oxidative phosphorylation, impossibility of a further acceleration of oxidative ATP synthesis, and dramatic drop in the phosphorylation potential. On the other hand, the each-step-activation mechanism allows maintenance of a high degree of the control exerted by ATP usage over the ATP turnover and oxygen consumption flux even at high energy demands and thus enables a potentially very large increase in ATP turnover. It is also shown that low oxygen concentration shifts the metabolic control from ATP usage to cytochrome oxidase and thus limits the oxidative ATP production.

  14. Mathematical modeling of cancer metabolism.

    Science.gov (United States)

    Medina, Miguel Ángel

    2018-04-01

    Systemic approaches are needed and useful for the study of the very complex issue of cancer. Modeling has a central position in these systemic approaches. Metabolic reprogramming is nowadays acknowledged as an essential hallmark of cancer. Mathematical modeling could contribute to a better understanding of cancer metabolic reprogramming and to identify new potential ways of therapeutic intervention. Herein, I review several alternative approaches to metabolic modeling and their current and future impact in oncology. Copyright © 2018 Elsevier B.V. All rights reserved.

  15. The JBEI quantitative metabolic modeling library (jQMM): a python library for modeling microbial metabolism

    DEFF Research Database (Denmark)

    Birkel, Garrett W.; Ghosh, Amit; Kumar, Vinay S.

    2017-01-01

    analysis, new methods for the effective use of the ever more readily available and abundant -omics data (i.e. transcriptomics, proteomics and metabolomics) are urgently needed.Results: The jQMM library presented here provides an open-source, Python-based framework for modeling internal metabolic fluxes......, it introduces the capability to use C-13 labeling experimental data to constrain comprehensive genome-scale models through a technique called two-scale C-13 Metabolic Flux Analysis (2S-C-13 MFA). In addition, the library includes a demonstration of a method that uses proteomics data to produce actionable...... insights to increase biofuel production. Finally, the use of the jQMM library is illustrated through the addition of several Jupyter notebook demonstration files that enhance reproducibility and provide the capability to be adapted to the user's specific needs.Conclusions: jQMM will facilitate the design...

  16. Metabolite-balancing techniques vs. 13C tracer experiments to determine metabolic fluxes in hybridoma cells.

    Science.gov (United States)

    Bonarius, H P; Timmerarends, B; de Gooijer, C D; Tramper, J

    The estimation of intracellular fluxes of mammalian cells using only mass balances of the relevant metabolites is not possible because the set of linear equations defined by these mass balances is underdetermined. In order to quantify fluxes in cyclic pathways the mass balance equations can be complemented with several constraints: (1) the mass balances of co-metabolites, such as ATP or NAD(P)H, (2) linear objective functions, (3) flux data obtained by isotopic-tracer experiments. Here, these three methods are compared for the analysis of fluxes in the primary metabolism of continuously cultured hybridoma cells. The significance of different theoretical constraints and different objective functions is discussed after comparing their resulting flux distributions to the fluxes determined using 13CO2 and 13C-lactate measurements of 1 - 13C-glucose-fed hybridoma cells. Metabolic fluxes estimated using the objective functions "maximize ATP" and "maximize NADH" are relatively similar to the experimentally determined fluxes. This is consistent with the observation that cancer cells, such as hybridomas, are metabolically hyperactive, and produce ATP and NADH regardless of the need for these cofactors. Copyright 1998 John Wiley & Sons, Inc.

  17. Rerouting of carbon flux in a glycogen mutant of cyanobacteria assessed via isotopically non-stationary 13 C metabolic flux analysis.

    Science.gov (United States)

    Hendry, John I; Prasannan, Charulata; Ma, Fangfang; Möllers, K Benedikt; Jaiswal, Damini; Digmurti, Madhuri; Allen, Doug K; Frigaard, Niels-Ulrik; Dasgupta, Santanu; Wangikar, Pramod P

    2017-10-01

    Cyanobacteria, which constitute a quantitatively dominant phylum, have attracted attention in biofuel applications due to favorable physiological characteristics, high photosynthetic efficiency and amenability to genetic manipulations. However, quantitative aspects of cyanobacterial metabolism have received limited attention. In the present study, we have performed isotopically non-stationary 13 C metabolic flux analysis (INST- 13 C-MFA) to analyze rerouting of carbon in a glycogen synthase deficient mutant strain (glgA-I glgA-II) of the model cyanobacterium Synechococcus sp. PCC 7002. During balanced photoautotrophic growth, 10-20% of the fixed carbon is stored in the form of glycogen via a pathway that is conserved across the cyanobacterial phylum. Our results show that deletion of glycogen synthase gene orchestrates cascading effects on carbon distribution in various parts of the metabolic network. Carbon that was originally destined to be incorporated into glycogen gets partially diverted toward alternate storage molecules such as glucosylglycerol and sucrose. The rest is partitioned within the metabolic network, primarily via glycolysis and tricarboxylic acid cycle. A lowered flux toward carbohydrate synthesis and an altered distribution at the glucose-1-phosphate node indicate flexibility in the network. Further, reversibility of glycogen biosynthesis reactions points toward the presence of futile cycles. Similar redistribution of carbon was also predicted by Flux Balance Analysis. The results are significant to metabolic engineering efforts with cyanobacteria where fixed carbon needs to be re-routed to products of interest. Biotechnol. Bioeng. 2017;114: 2298-2308. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  18. Deconfinement transition and flux-string models

    International Nuclear Information System (INIS)

    Momen, A.; Rosenzweig, C.

    1997-01-01

    Flux-string models can be used to study the deconfining phase transition. In this paper, we study the models proposed by Patel. We also study the large N c limits of Patel model. To discuss the validity of the mean field theory results, the one-loop Coleman-Weinberg effective potential is calculated for N c =3. We argue that the quantum corrections vanish at large N c when the energy of the so-called baryonic vertices scale with N c . copyright 1997 The American Physical Society

  19. Study of AMPK-Regulated Metabolic Fluxes in Neurons Using the Seahorse XFe Analyzer.

    Science.gov (United States)

    Marinangeli, Claudia; Kluza, Jérome; Marchetti, Philippe; Buée, Luc; Vingtdeux, Valérie

    2018-01-01

    AMP-activated protein kinase (AMPK) is the intracellular master energy sensor and metabolic regulator. AMPK is involved in cell energy homeostasis through the regulation of glycolytic flux and mitochondrial biogenesis. Interestingly, metabolic dysfunctions and AMPK deregulations are observed in many neurodegenerative diseases, including Alzheimer's. While these deregulations could play a key role in the development of these diseases, the study of metabolic fluxes has remained quite challenging and time-consuming. In this chapter, we describe the Seahorse XFe respirometry assay as a fundamental experimental tool to investigate the role of AMPK in controlling and modulating cell metabolic fluxes in living and intact differentiated primary neurons. The Seahorse XFe respirometry assay allows the real-time monitoring of glycolytic flux and mitochondrial respiration from different kind of cells, tissues, and isolated mitochondria. Here, we specify a protocol optimized for primary neuronal cells using several energy substrates such as glucose, pyruvate, lactate, glutamine, and ketone bodies. Nevertheless, this protocol can easily be adapted to monitor metabolic fluxes from other types of cells, tissues, or isolated mitochondria by taking into account the notes proposed for each key step of this assay.

  20. Dynamic metabolic flux analysis using B-splines to study the effects of temperature shift on CHO cell metabolism

    Directory of Open Access Journals (Sweden)

    Verónica S. Martínez

    2015-12-01

    Full Text Available Metabolic flux analysis (MFA is widely used to estimate intracellular fluxes. Conventional MFA, however, is limited to continuous cultures and the mid-exponential growth phase of batch cultures. Dynamic MFA (DMFA has emerged to characterize time-resolved metabolic fluxes for the entire culture period. Here, the linear DMFA approach was extended using B-spline fitting (B-DMFA to estimate mass balanced fluxes. Smoother fits were achieved using reduced number of knots and parameters. Additionally, computation time was greatly reduced using a new heuristic algorithm for knot placement. B-DMFA revealed that Chinese hamster ovary cells shifted from 37 °C to 32 °C maintained a constant IgG volume-specific productivity, whereas the productivity for the controls peaked during mid-exponential growth phase and declined afterward. The observed 42% increase in product titer at 32 °C was explained by a prolonged cell growth with high cell viability, a larger cell volume and a more stable volume-specific productivity. Keywords: Dynamic, Metabolism, Flux analysis, CHO cells, Temperature shift, B-spline curve fitting

  1. A method for accounting for maintenance costs in flux balance analysis improves the prediction of plant cell metabolic phenotypes under stress conditions.

    Science.gov (United States)

    Cheung, C Y Maurice; Williams, Thomas C R; Poolman, Mark G; Fell, David A; Ratcliffe, R George; Sweetlove, Lee J

    2013-09-01

    Flux balance models of metabolism generally utilize synthesis of biomass as the main determinant of intracellular fluxes. However, the biomass constraint alone is not sufficient to predict realistic fluxes in central heterotrophic metabolism of plant cells because of the major demand on the energy budget due to transport costs and cell maintenance. This major limitation can be addressed by incorporating transport steps into the metabolic model and by implementing a procedure that uses Pareto optimality analysis to explore the trade-off between ATP and NADPH production for maintenance. This leads to a method for predicting cell maintenance costs on the basis of the measured flux ratio between the oxidative steps of the oxidative pentose phosphate pathway and glycolysis. We show that accounting for transport and maintenance costs substantially improves the accuracy of fluxes predicted from a flux balance model of heterotrophic Arabidopsis cells in culture, irrespective of the objective function used in the analysis. Moreover, when the new method was applied to cells under control, elevated temperature and hyper-osmotic conditions, only elevated temperature led to a substantial increase in cell maintenance costs. It is concluded that the hyper-osmotic conditions tested did not impose a metabolic stress, in as much as the metabolic network is not forced to devote more resources to cell maintenance. © 2013 The Authors The Plant Journal © 2013 John Wiley & Sons Ltd.

  2. Genealogy profiling through strain improvement by using metabolic network analysis: metabolic flux genealogy of several generations of lysine-producing corynebacteria.

    Science.gov (United States)

    Wittmann, Christoph; Heinzle, Elmar

    2002-12-01

    A comprehensive approach of metabolite balancing, (13)C tracer studies, gas chromatography-mass spectrometry, matrix-assisted laser desorption ionization-time of flight mass spectrometry, and isotopomer modeling was applied for comparative metabolic network analysis of a genealogy of five successive generations of lysine-producing Corynebacterium glutamicum. The five strains examined (C. glutamicum ATCC 13032, 13287, 21253, 21526, and 21543) were previously obtained by random mutagenesis and selection. Throughout the genealogy, the lysine yield in batch cultures increased markedly from 1.2 to 24.9% relative to the glucose uptake flux. Strain optimization was accompanied by significant changes in intracellular flux distributions. The relative pentose phosphate pathway (PPP) flux successively increased, clearly corresponding to the product yield. Moreover, the anaplerotic net flux increased almost twofold as a consequence of concerted regulation of C(3) carboxylation and C(4) decarboxylation fluxes to cover the increased demand for lysine formation; thus, the overall increase was a consequence of concerted regulation of C(3) carboxylation and C(4) decarboxylation fluxes. The relative flux through isocitrate dehydrogenase dropped from 82.7% in the wild type to 59.9% in the lysine-producing mutants. In contrast to the NADPH demand, which increased from 109 to 172% due to the increasing lysine yield, the overall NADPH supply remained constant between 185 and 196%, resulting in a decrease in the apparent NADPH excess through strain optimization. Extrapolated to industrial lysine producers, the NADPH supply might become a limiting factor. The relative contributions of PPP and the tricarboxylic acid cycle to NADPH generation changed markedly, indicating that C. glutamicum is able to maintain a constant supply of NADPH under completely different flux conditions. Statistical analysis by a Monte Carlo approach revealed high precision for the estimated fluxes, underlining the

  3. Detection of Metabolic Fluxes of O and H Atoms into Intracellular Water in Mammalian Cells

    Science.gov (United States)

    Kreuzer, Helen W.; Quaroni, Luca; Podlesak, David W.; Zlateva, Theodora; Bollinger, Nikki; McAllister, Aaron; Lott, Michael J.; Hegg, Eric L.

    2012-01-01

    Metabolic processes result in the release and exchange of H and O atoms from organic material as well as some inorganic salts and gases. These fluxes of H and O atoms into intracellular water result in an isotopic gradient that can be measured experimentally. Using isotope ratio mass spectroscopy, we revealed that slightly over 50% of the H and O atoms in the intracellular water of exponentially-growing cultured Rat-1 fibroblasts were isotopically distinct from growth medium water. We then employed infrared spectromicroscopy to detect in real time the flux of H atoms in these same cells. Importantly, both of these techniques indicate that the H and O fluxes are dependent on metabolic processes; cells that are in lag phase or are quiescent exhibit a much smaller flux. In addition, water extracted from the muscle tissue of rats contained a population of H and O atoms that were isotopically distinct from body water, consistent with the results obtained using the cultured Rat-1 fibroblasts. Together these data demonstrate that metabolic processes produce fluxes of H and O atoms into intracellular water, and that these fluxes can be detected and measured in both cultured mammalian cells and in mammalian tissue. PMID:22848359

  4. Parameter optimization for surface flux transport models

    Science.gov (United States)

    Whitbread, T.; Yeates, A. R.; Muñoz-Jaramillo, A.; Petrie, G. J. D.

    2017-11-01

    Accurate prediction of solar activity calls for precise calibration of solar cycle models. Consequently we aim to find optimal parameters for models which describe the physical processes on the solar surface, which in turn act as proxies for what occurs in the interior and provide source terms for coronal models. We use a genetic algorithm to optimize surface flux transport models using National Solar Observatory (NSO) magnetogram data for Solar Cycle 23. This is applied to both a 1D model that inserts new magnetic flux in the form of idealized bipolar magnetic regions, and also to a 2D model that assimilates specific shapes of real active regions. The genetic algorithm searches for parameter sets (meridional flow speed and profile, supergranular diffusivity, initial magnetic field, and radial decay time) that produce the best fit between observed and simulated butterfly diagrams, weighted by a latitude-dependent error structure which reflects uncertainty in observations. Due to the easily adaptable nature of the 2D model, the optimization process is repeated for Cycles 21, 22, and 24 in order to analyse cycle-to-cycle variation of the optimal solution. We find that the ranges and optimal solutions for the various regimes are in reasonable agreement with results from the literature, both theoretical and observational. The optimal meridional flow profiles for each regime are almost entirely within observational bounds determined by magnetic feature tracking, with the 2D model being able to accommodate the mean observed profile more successfully. Differences between models appear to be important in deciding values for the diffusive and decay terms. In like fashion, differences in the behaviours of different solar cycles lead to contrasts in parameters defining the meridional flow and initial field strength.

  5. Prediction of Metabolic Flux Distribution from Gene Expression Data Based on the Flux Minimization Principle

    Science.gov (United States)

    2014-11-14

    biomass production. Although maximization of biomass produc- tion as used in E-Flux and FBA has been exploited to great advantage in many simulations and...due to appreciable production of fermentation products, particularly ethanol [37]. The experimentally obtained biomass yields by Lee et al. were 0.020...be larger than a certain level (e.g., 90% in our simulations ) of the theoretical maximal. Features of the E-Fmin Algorithm The main distinguishing

  6. Influence of the late winter bloom on migrant zooplankton metabolism and its implications on export fluxes

    Science.gov (United States)

    Putzeys, S.; Yebra, L.; Almeida, C.; Bécognée, P.; Hernández-León, S.

    2011-12-01

    Studies on carbon active fluxes due to diel migrants are scarce and critical for carbon flux models and biogeochemical estimates. We studied the temporal variability and vertical distribution of biomass, indices of feeding and respiration of the zooplanktonic community north off the Canary Islands during the end of the late winter bloom, in order to assess vertical carbon fluxes in this area. Biomass distribution during the day presented two dense layers of organisms at 0-200 m and around 500 m, whereas at night, most of the biomass concentrated in the epipelagic layer. The gut pigment flux (0.05-0.18 mgC·m - 2 ·d - 1 ) represented 0.22% of the estimated passive export flux (POC flux) while potential ingestion represented 3.91% of the POC (1.24-3.40 mgC·m - 2 ·d - 1 ). The active respiratory flux (0.50-1.36 mgC·m - 2 ·d - 1 ) was only 1.57% of the POC flux. The total carbon flux mediated by diel migrants (respiration plus potential ingestion) ranged between 3.37 and 9.22% of the POC flux; which is three-fold higher than calculating ingestion fluxes from gut pigments. Our results suggest that the fluxes by diel migrants play a small role in the downward flux of carbon in the open ocean during the post-bloom period.

  7. Metabolic fluxes in the central carbon metabolism of Dinoroseobacter shibae and Phaeobacter gallaeciensis, two members of the marine Roseobacter clade

    Directory of Open Access Journals (Sweden)

    Rabus Ralf

    2009-09-01

    Full Text Available Abstract Background In the present work the central carbon metabolism of Dinoroseobacter shibae and Phaeobacter gallaeciensis was studied at the level of metabolic fluxes. These two strains belong to the marine Roseobacter clade, a dominant bacterial group in various marine habitats, and represent surface-associated, biofilm-forming growth (P. gallaeciensis and symbiotic growth with eukaryotic algae (D. shibae. Based on information from recently sequenced genomes, a rich repertoire of pathways has been identified in the carbon core metabolism of these organisms, but little is known about the actual contribution of the various reactions in vivo. Results Using 13C labelling techniques in specifically designed experiments, it could be shown that glucose-grown cells of D. shibae catabolise the carbon source exclusively via the Entner-Doudoroff pathway, whereas alternative routes of glycolysis and the pentose phosphate pathway are obviously utilised for anabolic purposes only. Enzyme assays confirmed this flux pattern and link the lack of glycolytic flux to the absence of phosphofructokinase activity. The previously suggested formation of phosphoenolpyruvate from pyruvate during mixotrophic CO2 assimilation was found to be inactive under the conditions studied. Moreover, it could be shown that pyruvate carboxylase is involved in CO2 assimilation and that the cyclic respiratory mode of the TCA cycle is utilised. Interestingly, the use of intracellular pathways was highly similar for P. gallaeciensis. Conclusion The present study reveals the first insight into pathway utilisation within the Roseobacter group. Fluxes through major intracellular pathways of the central carbon metabolism, which are closely linked to the various important traits found for the Roseobacter clade, could be determined. The close similarity of fluxes between the two physiologically rather different species might provide the first indication of more general key properties among

  8. The role of metabolism in modulating CO2 fluxes in boreal lakes

    Science.gov (United States)

    Bogard, Matthew J.; del Giorgio, Paul A.

    2016-10-01

    Lake CO2 emissions are increasingly recognized as an important component of the global CO2 cycle, yet the origin of these emissions is not clear, as specific contributions from metabolism and in-lake cycling, versus external inputs, are not well defined. To assess the coupling of lake metabolism with CO2 concentrations and fluxes, we estimated steady state ratios of gross primary production to respiration (GPP:R) and rates of net ecosystem production (NEP = GPP-R) from surface water O2 dynamics (concentration and stable isotopes) in 187 boreal lakes spanning long environmental gradients. Our findings suggest that internal metabolism plays a dominant role in regulating CO2 fluxes in most lakes, but this pattern only emerges when examined at a resolution that accounts for the vastly differing relationships between lake metabolism and CO2 fluxes. Fluxes of CO2 exceeded those from NEP in over half the lakes, but unexpectedly, these effects were most common and typically largest in a subset ( 30% of total) of net autotrophic lakes that nevertheless emitted CO2. Equally surprising, we found no environmental characteristics that distinguished this category from the more common net heterotrophic, CO2 outgassing lakes. Excess CO2 fluxes relative to NEP were best predicted by catchment structure and hydrologic properties, and we infer from a combination of methods that both catchment inputs and internal anaerobic processes may have contributed this excess CO2. Together, our findings show that the link between lake metabolism and CO2 fluxes is often strong but can vary widely across the boreal biome, having important implications for catchment-wide C budgets.

  9. Metabolic flux profiling of recombinant protein secreting Pichia pastoris growing on glucose:methanol mixtures

    Science.gov (United States)

    2012-01-01

    Background The methylotrophic yeast Pichia pastoris has emerged as one of the most promising yeast hosts for the production of heterologous proteins. Mixed feeds of methanol and a multicarbon source instead of methanol as sole carbon source have been shown to improve product productivities and alleviate metabolic burden derived from protein production. Nevertheless, systematic quantitative studies on the relationships between the central metabolism and recombinant protein production in P. pastoris are still rather limited, particularly when growing this yeast on mixed carbon sources, thus hampering future metabolic network engineering strategies for improved protein production. Results The metabolic flux distribution in the central metabolism of P. pastoris growing on a mixed feed of glucose and methanol was analyzed by Metabolic Flux Analysis (MFA) using 13C-NMR-derived constraints. For this purpose, we defined new flux ratios for methanol assimilation pathways in P. pastoris cells growing on glucose:methanol mixtures. By using this experimental approach, the metabolic burden caused by the overexpression and secretion of a Rhizopus oryzae lipase (Rol) in P. pastoris was further analyzed. This protein has been previously shown to trigger the unfolded protein response in P. pastoris. A series of 13C-tracer experiments were performed on aerobic chemostat cultivations with a control and two different Rol producing strains growing at a dilution rate of 0.09 h−1 using a glucose:methanol 80:20 (w/w) mix as carbon source. The MFA performed in this study reveals a significant redistristribution of carbon fluxes in the central carbon metabolism when comparing the two recombinant strains vs the control strain, reflected in increased glycolytic, TCA cycle and NADH regeneration fluxes, as well as higher methanol dissimilation rates. Conclusions Overall, a further 13C-based MFA development to characterise the central metabolism of methylotrophic yeasts when growing on mixed

  10. Metabolic flux profiling of recombinant protein secreting Pichia pastoris growing on glucose:methanol mixtures

    Directory of Open Access Journals (Sweden)

    Jordà Joel

    2012-05-01

    Full Text Available Abstract Background The methylotrophic yeast Pichia pastoris has emerged as one of the most promising yeast hosts for the production of heterologous proteins. Mixed feeds of methanol and a multicarbon source instead of methanol as sole carbon source have been shown to improve product productivities and alleviate metabolic burden derived from protein production. Nevertheless, systematic quantitative studies on the relationships between the central metabolism and recombinant protein production in P. pastoris are still rather limited, particularly when growing this yeast on mixed carbon sources, thus hampering future metabolic network engineering strategies for improved protein production. Results The metabolic flux distribution in the central metabolism of P. pastoris growing on a mixed feed of glucose and methanol was analyzed by Metabolic Flux Analysis (MFA using 13C-NMR-derived constraints. For this purpose, we defined new flux ratios for methanol assimilation pathways in P. pastoris cells growing on glucose:methanol mixtures. By using this experimental approach, the metabolic burden caused by the overexpression and secretion of a Rhizopus oryzae lipase (Rol in P. pastoris was further analyzed. This protein has been previously shown to trigger the unfolded protein response in P. pastoris. A series of 13C-tracer experiments were performed on aerobic chemostat cultivations with a control and two different Rol producing strains growing at a dilution rate of 0.09 h−1 using a glucose:methanol 80:20 (w/w mix as carbon source. The MFA performed in this study reveals a significant redistristribution of carbon fluxes in the central carbon metabolism when comparing the two recombinant strains vs the control strain, reflected in increased glycolytic, TCA cycle and NADH regeneration fluxes, as well as higher methanol dissimilation rates. Conclusions Overall, a further 13C-based MFA development to characterise the central metabolism of methylotrophic

  11. Genome scale metabolic modeling of cancer

    DEFF Research Database (Denmark)

    Nilsson, Avlant; Nielsen, Jens

    2017-01-01

    of metabolism which allows simulation and hypotheses testing of metabolic strategies. It has successfully been applied to many microorganisms and is now used to study cancer metabolism. Generic models of human metabolism have been reconstructed based on the existence of metabolic genes in the human genome......Cancer cells reprogram metabolism to support rapid proliferation and survival. Energy metabolism is particularly important for growth and genes encoding enzymes involved in energy metabolism are frequently altered in cancer cells. A genome scale metabolic model (GEM) is a mathematical formalization...

  12. Metabolic Models of Protein Allocation Call for the Kinetome

    DEFF Research Database (Denmark)

    Nilsson, Avlant; Nielsen, Jens; Palsson, Bernhard

    2017-01-01

    The flux of metabolites in the living cell depend on enzyme activities. Recently, many metabolic phenotypes have been explained by computer models that incorporate enzyme activity data. To move further, the scientific community needs to measure the kinetics of all enzymes in a systematic way....

  13. The elliptic model for communication fluxes

    International Nuclear Information System (INIS)

    Herrera-Yagüe, C; Schneider, C M; González, M C; Smoreda, Z; Couronné, T; Zufiria, P J

    2014-01-01

    In this paper, a model (called the elliptic model) is proposed to estimate the number of social ties between two locations using population data in a similar manner to how transportation research deals with trips. To overcome the asymmetry of transportation models, the new model considers that the number of relationships between two locations is inversely proportional to the population in the ellipse whose foci are in these two locations. The elliptic model is evaluated by considering the anonymous communications patterns of 25 million users from three different countries, where a location has been assigned to each user based on their most used phone tower or billing zip code. With this information, spatial social networks are built at three levels of resolution: tower, city and region for each of the three countries. The elliptic model achieves a similar performance when predicting communication fluxes as transportation models do when predicting trips. This shows that human relationships are influenced at least as much by geography as is human mobility. (paper)

  14. An odor flux model for cattle feedlots

    Energy Technology Data Exchange (ETDEWEB)

    Ormerod, R.J. [Dames & Moore, Brisbane (Australia)

    1994-12-31

    Odor nuisance associated with cattle feedlots has been an issue of major interest and concern to regulators, rural communities and the beef industry in Australia over the past decade. Methods of assessing the likely impacts of new feedlots on community odor exposure are still being developed, but in the past few years much has been learnt about the processes of odor generation, flux and dispersion as well as the acceptability of feedlot odor to exposed communities. This paper outlines a model which simulates the complex physical and chemical processes leading to odor emissions in a simple and practical framework. The model, named BULSMEL, has been developed as a response to regulatory requirements for quantitative assessments of odor impact. It will continue to be refined as more data are gathered.

  15. 13C metabolic flux analysis: optimal design of isotopic labeling experiments.

    Science.gov (United States)

    Antoniewicz, Maciek R

    2013-12-01

    Measuring fluxes by 13C metabolic flux analysis (13C-MFA) has become a key activity in chemical and pharmaceutical biotechnology. Optimal design of isotopic labeling experiments is of central importance to 13C-MFA as it determines the precision with which fluxes can be estimated. Traditional methods for selecting isotopic tracers and labeling measurements did not fully utilize the power of 13C-MFA. Recently, new approaches were developed for optimal design of isotopic labeling experiments based on parallel labeling experiments and algorithms for rational selection of tracers. In addition, advanced isotopic labeling measurements were developed based on tandem mass spectrometry. Combined, these approaches can dramatically improve the quality of 13C-MFA results with important applications in metabolic engineering and biotechnology. Copyright © 2013 Elsevier Ltd. All rights reserved.

  16. Towards high resolution analysis of metabolic flux in cells and tissues.

    Science.gov (United States)

    Sims, James K; Manteiga, Sara; Lee, Kyongbum

    2013-10-01

    Metabolism extracts chemical energy from nutrients, uses this energy to form building blocks for biosynthesis, and interconverts between various small molecules that coordinate the activities of cellular pathways. The metabolic state of a cell is increasingly recognized to determine the phenotype of not only metabolically active cell types such as liver, muscle, and adipose, but also other specialized cell types such as neurons and immune cells. This review focuses on methods to quantify intracellular reaction flux as a measure of cellular metabolic activity, with emphasis on studies involving cells of mammalian tissue. Two key areas are highlighted for future development, single cell metabolomics and noninvasive imaging, which could enable spatiotemporally resolved analysis and thereby overcome issues of heterogeneity, a distinctive feature of tissue metabolism. Copyright © 2013 Elsevier Ltd. All rights reserved.

  17. Analysis of Metabolic Pathways and Fluxes in a Newly Discovered Thermophilic and Ethanol-Tolerant Geobacillus Strain

    Energy Technology Data Exchange (ETDEWEB)

    Tang, Yinjie J.; Sapra, Rajat; Joyner, Dominique; Hazen, Terry C.; Myers, Samuel; Reichmuth, David; Blanch, Harvey; Keasling, Jay D.

    2009-01-20

    A recently discovered thermophilic bacterium, Geobacillus thermoglucosidasius M10EXG, ferments a range of C5 (e.g., xylose) and C6 sugars (e.g., glucose) and istolerant to high ethanol concentrations (10percent, v/v). We have investigated the central metabolism of this bacterium using both in vitro enzyme assays and 13C-based flux analysis to provide insights into the physiological properties of this extremophile and explore its metabolism for bio-ethanol or other bioprocess applications. Our findings show that glucose metabolism in G. thermoglucosidasius M10EXG proceeds via glycolysis, the pentose phosphate pathway, and the TCA cycle; the Entner?Doudoroff pathway and transhydrogenase activity were not detected. Anaplerotic reactions (including the glyoxylate shunt, pyruvate carboxylase, and phosphoenolpyruvate carboxykinase) were active, but fluxes through those pathways could not be accuratelydetermined using amino acid labeling. When growth conditions were switched from aerobic to micro-aerobic conditions, fluxes (based on a normalized glucose uptake rate of 100 units (g DCW)-1 h-1) through the TCA cycle and oxidative pentose phosphate pathway were reduced from 64+-3 to 25+-2 and from 30+-2 to 19+-2, respectively. The carbon flux under micro-aerobic growth was directed formate. Under fully anerobic conditions, G. thermoglucosidasius M10EXG used a mixed acid fermentation process and exhibited a maximum ethanol yield of 0.38+-0.07 mol mol-1 glucose. In silico flux balance modeling demonstrates that lactate and acetate production from G. thermoglucosidasius M10EXG reduces the maximum ethanol yieldby approximately threefold, thus indicating that both pathways should be modified to maximize ethanol production.

  18. Microalgal Metabolic Network Model Refinement through High-Throughput Functional Metabolic Profiling

    International Nuclear Information System (INIS)

    Chaiboonchoe, Amphun; Dohai, Bushra Saeed; Cai, Hong; Nelson, David R.; Jijakli, Kenan; Salehi-Ashtiani, Kourosh

    2014-01-01

    Metabolic modeling provides the means to define metabolic processes at a systems level; however, genome-scale metabolic models often remain incomplete in their description of metabolic networks and may include reactions that are experimentally unverified. This shortcoming is exacerbated in reconstructed models of newly isolated algal species, as there may be little to no biochemical evidence available for the metabolism of such isolates. The phenotype microarray (PM) technology (Biolog, Hayward, CA, USA) provides an efficient, high-throughput method to functionally define cellular metabolic activities in response to a large array of entry metabolites. The platform can experimentally verify many of the unverified reactions in a network model as well as identify missing or new reactions in the reconstructed metabolic model. The PM technology has been used for metabolic phenotyping of non-photosynthetic bacteria and fungi, but it has not been reported for the phenotyping of microalgae. Here, we introduce the use of PM assays in a systematic way to the study of microalgae, applying it specifically to the green microalgal model species Chlamydomonas reinhardtii. The results obtained in this study validate a number of existing annotated metabolic reactions and identify a number of novel and unexpected metabolites. The obtained information was used to expand and refine the existing COBRA-based C. reinhardtii metabolic network model iRC1080. Over 254 reactions were added to the network, and the effects of these additions on flux distribution within the network are described. The novel reactions include the support of metabolism by a number of d-amino acids, l-dipeptides, and l-tripeptides as nitrogen sources, as well as support of cellular respiration by cysteamine-S-phosphate as a phosphorus source. The protocol developed here can be used as a foundation to functionally profile other microalgae such as known microalgae mutants and novel isolates.

  19. Microalgal Metabolic Network Model Refinement through High-Throughput Functional Metabolic Profiling

    Energy Technology Data Exchange (ETDEWEB)

    Chaiboonchoe, Amphun; Dohai, Bushra Saeed; Cai, Hong; Nelson, David R. [Division of Science and Math, New York University Abu Dhabi, Abu Dhabi (United Arab Emirates); Center for Genomics and Systems Biology (CGSB), New York University Abu Dhabi Institute, Abu Dhabi (United Arab Emirates); Jijakli, Kenan [Division of Science and Math, New York University Abu Dhabi, Abu Dhabi (United Arab Emirates); Center for Genomics and Systems Biology (CGSB), New York University Abu Dhabi Institute, Abu Dhabi (United Arab Emirates); Engineering Division, Biofinery, Manhattan, KS (United States); Salehi-Ashtiani, Kourosh, E-mail: ksa3@nyu.edu [Division of Science and Math, New York University Abu Dhabi, Abu Dhabi (United Arab Emirates); Center for Genomics and Systems Biology (CGSB), New York University Abu Dhabi Institute, Abu Dhabi (United Arab Emirates)

    2014-12-10

    Metabolic modeling provides the means to define metabolic processes at a systems level; however, genome-scale metabolic models often remain incomplete in their description of metabolic networks and may include reactions that are experimentally unverified. This shortcoming is exacerbated in reconstructed models of newly isolated algal species, as there may be little to no biochemical evidence available for the metabolism of such isolates. The phenotype microarray (PM) technology (Biolog, Hayward, CA, USA) provides an efficient, high-throughput method to functionally define cellular metabolic activities in response to a large array of entry metabolites. The platform can experimentally verify many of the unverified reactions in a network model as well as identify missing or new reactions in the reconstructed metabolic model. The PM technology has been used for metabolic phenotyping of non-photosynthetic bacteria and fungi, but it has not been reported for the phenotyping of microalgae. Here, we introduce the use of PM assays in a systematic way to the study of microalgae, applying it specifically to the green microalgal model species Chlamydomonas reinhardtii. The results obtained in this study validate a number of existing annotated metabolic reactions and identify a number of novel and unexpected metabolites. The obtained information was used to expand and refine the existing COBRA-based C. reinhardtii metabolic network model iRC1080. Over 254 reactions were added to the network, and the effects of these additions on flux distribution within the network are described. The novel reactions include the support of metabolism by a number of d-amino acids, l-dipeptides, and l-tripeptides as nitrogen sources, as well as support of cellular respiration by cysteamine-S-phosphate as a phosphorus source. The protocol developed here can be used as a foundation to functionally profile other microalgae such as known microalgae mutants and novel isolates.

  20. Shigella reroutes host cell central metabolism to obtain high-flux nutrient supply for vigorous intracellular growth.

    Science.gov (United States)

    Kentner, David; Martano, Giuseppe; Callon, Morgane; Chiquet, Petra; Brodmann, Maj; Burton, Olga; Wahlander, Asa; Nanni, Paolo; Delmotte, Nathanaël; Grossmann, Jonas; Limenitakis, Julien; Schlapbach, Ralph; Kiefer, Patrick; Vorholt, Julia A; Hiller, Sebastian; Bumann, Dirk

    2014-07-08

    Shigella flexneri proliferate in infected human epithelial cells at exceptionally high rates. This vigorous growth has important consequences for rapid progression to life-threatening bloody diarrhea, but the underlying metabolic mechanisms remain poorly understood. Here, we used metabolomics, proteomics, and genetic experiments to determine host and Shigella metabolism during infection in a cell culture model. The data suggest that infected host cells maintain largely normal fluxes through glycolytic pathways, but the entire output of these pathways is captured by Shigella, most likely in the form of pyruvate. This striking strategy provides Shigella with an abundant favorable energy source, while preserving host cell ATP generation, energy charge maintenance, and survival, despite ongoing vigorous exploitation. Shigella uses a simple three-step pathway to metabolize pyruvate at high rates with acetate as an excreted waste product. The crucial role of this pathway for Shigella intracellular growth suggests targets for antimicrobial chemotherapy of this devastating disease.

  1. Incorporating Protein Biosynthesis into the Saccharomyces cerevisiae Genome-scale Metabolic Model

    DEFF Research Database (Denmark)

    Olivares Hernandez, Roberto

    Based on stoichiometric biochemical equations that occur into the cell, the genome-scale metabolic models can quantify the metabolic fluxes, which are regarded as the final representation of the physiological state of the cell. For Saccharomyces Cerevisiae the genome scale model has been construc......Based on stoichiometric biochemical equations that occur into the cell, the genome-scale metabolic models can quantify the metabolic fluxes, which are regarded as the final representation of the physiological state of the cell. For Saccharomyces Cerevisiae the genome scale model has been...

  2. Flux-Enabled Exploration of the Role of Sip1 in Galactose Yeast Metabolism

    Directory of Open Access Journals (Sweden)

    Christopher M. Shymansky

    2017-05-01

    Full Text Available 13C metabolic flux analysis (13C MFA is an important systems biology technique that has been used to investigate microbial metabolism for decades. The heterotrimer Snf1 kinase complex plays a key role in the preference Saccharomyces cerevisiae exhibits for glucose over galactose, a phenomenon known as glucose repression or carbon catabolite repression. The SIP1 gene, encoding a part of this complex, has received little attention, presumably, because its knockout lacks a growth phenotype. We present a fluxomic investigation of the relative effects of the presence of galactose in classically glucose-repressing media and/or knockout of SIP1 using a multi-scale variant of 13C MFA known as 2-Scale 13C metabolic flux analysis (2S-13C MFA. In this study, all strains have the galactose metabolism deactivated (gal1Δ background so as to be able to separate the metabolic effects purely related to glucose repression from those arising from galactose metabolism. The resulting flux profiles reveal that the presence of galactose in classically glucose-repressing conditions, for a CEN.PK113-7D gal1Δ background, results in a substantial decrease in pentose phosphate pathway (PPP flux and increased flow from cytosolic pyruvate and malate through the mitochondria toward cytosolic branched-chain amino acid biosynthesis. These fluxomic redistributions are accompanied by a higher maximum specific growth rate, both seemingly in violation of glucose repression. Deletion of SIP1 in the CEN.PK113-7D gal1Δ cells grown in mixed glucose/galactose medium results in a further increase. Knockout of this gene in cells grown in glucose-only medium results in no change in growth rate and a corresponding decrease in glucose and ethanol exchange fluxes and flux through pathways involved in aspartate/threonine biosynthesis. Glucose repression appears to be violated at a 1/10 ratio of galactose-to-glucose. Based on the scientific literature, we may have conducted our experiments

  3. In vivo dynamics of galactose metabolism in Saccharomyces cerevisiae: Metabolic fluxes and metabolite levels

    DEFF Research Database (Denmark)

    Østergaard, Simon; Olsson, Lisbeth; Nielsen, Jens

    2001-01-01

    The dynamics of galactose metabolism in Saccharomyces cerevisiae was studied by analyzing the metabolic response of the CEN.PK 113-7D wild-type strain when exposed to a galactose pulse during aerobic growth in a galactose-limited steady-state cultivation at a dilution rate of 0.097 h(-1). A fast...

  4. Flux Balance Analysis Inspired Bioprocess Upgrading for Lycopene Production by a Metabolically Engineered Strain of Yarrowia lipolytica

    Directory of Open Access Journals (Sweden)

    Komi Nambou

    2015-12-01

    Full Text Available Genome-scale metabolic models embody a significant advantage of systems biology since their applications as metabolic flux simulation models enable predictions for the production of industrially-interesting metabolites. The biotechnological production of lycopene from Yarrowia lipolytica is an emerging scope that has not been fully scrutinized, especially for what concerns cultivation conditions of newly generated engineered strains. In this study, by combining flux balance analysis (FBA and Plackett-Burman design, we screened chemicals for lycopene production from a metabolically engineered strain of Y. lipolytica. Lycopene concentrations of 126 and 242 mg/L were achieved correspondingly from the FBA-independent and the FBA-assisted designed media in fed-batch cultivation mode. Transcriptional studies revealed upregulations of heterologous genes in media designed according to FBA, thus implying the efficiency of model predictions. Our study will potentially support upgraded lycopene and other terpenoids production from existing or prospect bioengineered strains of Y. lipolytica and/or closely related yeast species.

  5. Metabolic flux analysis of Cyanothece sp. ATCC 51142 under mixotrophic conditions.

    Science.gov (United States)

    Alagesan, Swathi; Gaudana, Sandeep B; Sinha, Avinash; Wangikar, Pramod P

    2013-11-01

    Cyanobacteria are a group of photosynthetic prokaryotes capable of utilizing solar energy to fix atmospheric carbon dioxide to biomass. Despite several "proof of principle" studies, low product yield is an impediment in commercialization of cyanobacteria-derived biofuels. Estimation of intracellular reaction rates by (13)C metabolic flux analysis ((13)C-MFA) would be a step toward enhancing biofuel yield via metabolic engineering. We report (13)C-MFA for Cyanothece sp. ATCC 51142, a unicellular nitrogen-fixing cyanobacterium, known for enhanced hydrogen yield under mixotrophic conditions. Rates of reactions in the central carbon metabolism under nitrogen-fixing and -non-fixing conditions were estimated by monitoring the competitive incorporation of (12)C and (13)C from unlabeled CO2 and uniformly labeled glycerol, respectively, into terminal metabolites such as amino acids. The observed labeling patterns suggest mixotrophic growth under both the conditions, with a larger fraction of unlabeled carbon in nitrate-sufficient cultures asserting a greater contribution of carbon fixation by photosynthesis and an anaplerotic pathway. Indeed, flux analysis complements the higher growth observed under nitrate-sufficient conditions. On the other hand, the flux through the oxidative pentose phosphate pathway and tricarboxylic acid cycle was greater in nitrate-deficient conditions, possibly to supply the precursors and reducing equivalents needed for nitrogen fixation. In addition, an enhanced flux through fructose-6-phosphate phosphoketolase possibly suggests the organism's preferred mode under nitrogen-fixing conditions. The (13)C-MFA results complement the reported predictions by flux balance analysis and provide quantitative insight into the organism's distinct metabolic features under nitrogen-fixing and -non-fixing conditions.

  6. ¹³C-based metabolic flux analysis of Saccharomyces cerevisiae with a reduced Crabtree effect.

    Science.gov (United States)

    Kajihata, Shuichi; Matsuda, Fumio; Yoshimi, Mika; Hayakawa, Kenshi; Furusawa, Chikara; Kanda, Akihisa; Shimizu, Hiroshi

    2015-08-01

    Saccharomyces cerevisiae shows a Crabtree effect that produces ethanol in a high glucose concentration even under fully aerobic condition. For efficient production of cake yeast or compressed yeast for baking, ethanol by-production is not desired since glucose limited chemostat or fed-batch cultivations are performed to suppress the Crabtree effect. In this study, the (13)C-based metabolic flux analysis ((13)C-MFA) was performed for the S288C derived S. cerevisiae strain to characterize a metabolic state under the reduced Crabtree effect. S. cerevisiae cells were cultured at a low dilution rate (0.1 h(-1)) under the glucose-limited chemostat condition. The estimated metabolic flux distribution showed that the acetyl-CoA in mitochondria was mainly produced from pyruvate by pyruvate dehydrogenase (PDH) reaction and that the level of the metabolic flux through the pentose phosphate pathway was much higher than that of the Embden-Meyerhof-Parnas pathway, which contributes to high biomass yield at low dilution rate by supplying NADPH required for cell growth. Copyright © 2015 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

  7. Magnetic flux tube models in superstring theory

    CERN Document Server

    Russo, Jorge G

    1996-01-01

    Superstring models describing curved 4-dimensional magnetic flux tube backgrounds are exactly solvable in terms of free fields. We consider the simplest model of this type (corresponding to `Kaluza-Klein' Melvin background). Its 2d action has a flat but topologically non-trivial 10-dimensional target space (there is a mixing of angular coordinate of the 2-plane with an internal compact coordinate). We demonstrate that this theory has broken supersymmetry but is perturbatively stable if the radius R of the internal coordinate is larger than R_0=\\sqrt{2\\a'}. In the Green-Schwarz formulation the supersymmetry breaking is a consequence of the presence of a flat but non-trivial connection in the fermionic terms in the action. For R R/2\\a' there appear instabilities corresponding to tachyonic winding states. The torus partition function Z(q,R) is finite for R > R_0 (and vanishes for qR=2n, n=integer). At the special points qR=2n (2n+1) the model is equivalent to the free superstring theory compactified on a circle...

  8. Dynamic modeling of lactic acid fermentation metabolism with Lactococcus lactis.

    Science.gov (United States)

    Oh, Euhlim; Lu, Mingshou; Park, Changhun; Park, Changhun; Oh, Han Bin; Lee, Sang Yup; Lee, Jinwon

    2011-02-01

    A dynamic model of lactic acid fermentation using Lactococcus lactis was constructed, and a metabolic flux analysis (MFA) and metabolic control analysis (MCA) were performed to reveal an intensive metabolic understanding of lactic acid bacteria (LAB). The parameter estimation was conducted with COPASI software to construct a more accurate metabolic model. The experimental data used in the parameter estimation were obtained from an LC-MS/ MS analysis and time-course simulation study. The MFA results were a reasonable explanation of the experimental data. Through the parameter estimation, the metabolic system of lactic acid bacteria can be thoroughly understood through comparisons with the original parameters. The coefficients derived from the MCA indicated that the reaction rate of L-lactate dehydrogenase was activated by fructose 1,6-bisphosphate and pyruvate, and pyruvate appeared to be a stronger activator of L-lactate dehydrogenase than fructose 1,6-bisphosphate. Additionally, pyruvate acted as an inhibitor to pyruvate kinase and the phosphotransferase system. Glucose 6-phosphate and phosphoenolpyruvate showed activation effects on pyruvate kinase. Hexose transporter was the strongest effector on the flux through L-lactate dehydrogenase. The concentration control coefficient (CCC) showed similar results to the flux control coefficient (FCC).

  9. Flux analysis of central metabolic pathways in the Fe(III)-reducing organism Geobacter metallireducens via 13C isotopiclabeling

    Energy Technology Data Exchange (ETDEWEB)

    Tang, Yinjie J.; Chakraborty, Romy; Martin, Hector Garcia; Chu,Jeannie; Hazen, Terry C.; Keasling, Jay D.

    2007-08-13

    We analyzed the carbon fluxes in the central metabolism ofGeobacter metallireducens strain GS-15 using 13C isotopomer modeling.Acetate labeled in the 1st or 2nd position was the sole carbon source,and Fe-NTA was the sole terminal electron acceptor. The measured labeledacetate uptake rate was 21 mmol/gdw/h in the exponential growth phase.The resulting isotope labeling pattern of amino acids allowed an accuratedetermination of the in vivo global metabolic reaction rates (fluxes)through the central metabolic pathways using a computational isotopomermodel. The model indicated that over 90 percent of the acetate wascompletely oxidized to CO2 via a complete tricarboxylic acid (TCA) cyclewhile reducing iron. Pyruvate carboxylase and phosphoenolpyruvatecarboxykinase were present under these conditions, but enzymes in theglyoxylate shunt and malic enzyme were absent. Gluconeogenesis and thepentose phosphate pathway were mainly employed for biosynthesis andaccounted for less than 3 percent of total carbon consumption. The modelalso indicated surprisingly high reversibility in the reaction betweenoxoglutarate and succinate. This step operates close to the thermodynamicequilibrium possibly because succinate is synthesized via a transferasereaction, and its product, acetyl-CoA, inhibits the conversion ofoxoglutarate to succinate. These findings enable a better understandingof the relationship between genome annotation and extant metabolicpathways in G. metallireducens.

  10. Redistribution of metabolic fluxes in Chlorella protothecoides by variation of media nitrogen concentration

    Directory of Open Access Journals (Sweden)

    Saratram Gopalakrishnan

    2015-12-01

    Full Text Available In this study, the Elementary Metabolite Unit (EMU algorithm was employed to calculate intracellular fluxes for Chlorella protothecoides using previously generated growth and mass spec data. While the flux through glycolysis remained relatively constant, the pentose phosphate pathway (PPP flux increased from 3% to 20% of the glucose uptake during nitrogen-limited growth. The TCA cycle flux decreased from 94% to 38% during nitrogen-limited growth while the flux of acetyl-CoA into lipids increased from 58% to 109% of the glucose uptake, increasing total lipid accumulation. Phosphoenolpyruvate carboxylase (PEPCase activity was higher during nitrogen-sufficient growth. The glyoxylate shunt was found to be partially active in both cases, indicating the nutrient nature has an impact on flux distribution. It was found that the total NADPH supply within the cell remained almost constant under both conditions. In summary, algal cells substantially reorganize their metabolism during the switch from carbon-limited (nitrogen-sufficient to nitrogen-limited (carbon-sufficient growth. Keywords: Microalgae, Biofuels, Chlorella, MFA, EMU algorithm

  11. Fast modeling of flux trapping cascaded explosively driven magnetic flux compression generators.

    Science.gov (United States)

    Wang, Yuwei; Zhang, Jiande; Chen, Dongqun; Cao, Shengguang; Li, Da; Liu, Chebo

    2013-01-01

    To predict the performance of flux trapping cascaded flux compression generators, a calculation model based on an equivalent circuit is investigated. The system circuit is analyzed according to its operation characteristics in different steps. Flux conservation coefficients are added to the driving terms of circuit differential equations to account for intrinsic flux losses. To calculate the currents in the circuit by solving the circuit equations, a simple zero-dimensional model is used to calculate the time-varying inductance and dc resistance of the generator. Then a fast computer code is programmed based on this calculation model. As an example, a two-staged flux trapping generator is simulated by using this computer code. Good agreements are achieved by comparing the simulation results with the measurements. Furthermore, it is obvious that this fast calculation model can be easily applied to predict performances of other flux trapping cascaded flux compression generators with complex structures such as conical stator or conical armature sections and so on for design purpose.

  12. Energetics of glucose metabolism: a phenomenological approach to metabolic network modeling.

    Science.gov (United States)

    Diederichs, Frank

    2010-08-12

    A new formalism to describe metabolic fluxes as well as membrane transport processes was developed. The new flux equations are comparable to other phenomenological laws. Michaelis-Menten like expressions, as well as flux equations of nonequilibrium thermodynamics, can be regarded as special cases of these new equations. For metabolic network modeling, variable conductances and driving forces are required to enable pathway control and to allow a rapid response to perturbations. When applied to oxidative phosphorylation, results of simulations show that whole oxidative phosphorylation cannot be described as a two-flux-system according to nonequilibrium thermodynamics, although all coupled reactions per se fulfill the equations of this theory. Simulations show that activation of ATP-coupled load reactions plus glucose oxidation is brought about by an increase of only two different conductances: a [Ca(2+)] dependent increase of cytosolic load conductances, and an increase of phosphofructokinase conductance by [AMP], which in turn becomes increased through [ADP] generation by those load reactions. In ventricular myocytes, this feedback mechanism is sufficient to increase cellular power output and O(2) consumption several fold, without any appreciable impairment of energetic parameters. Glucose oxidation proceeds near maximal power output, since transformed input and output conductances are nearly equal, yielding an efficiency of about 0.5. This conductance matching is fulfilled also by glucose oxidation of β-cells. But, as a price for the metabolic mechanism of glucose recognition, β-cells have only a limited capability to increase their power output.

  13. (13)C-metabolic flux analysis in S-adenosyl-L-methionine production by Saccharomyces cerevisiae.

    Science.gov (United States)

    Hayakawa, Kenshi; Kajihata, Shuichi; Matsuda, Fumio; Shimizu, Hiroshi

    2015-11-01

    S-Adenosyl-L-methionine (SAM) is a major biological methyl group donor, and is used as a nutritional supplement and prescription drug. Yeast is used for the industrial production of SAM owing to its high intracellular SAM concentrations. To determine the regulation mechanisms responsible for such high SAM production, (13)C-metabolic flux analysis ((13)C-MFA) was conducted to compare the flux distributions in the central metabolism between Kyokai no. 6 (high SAM-producing) and S288C (control) strains. (13)C-MFA showed that the levels of tricarboxylic acid (TCA) cycle flux in SAM-overproducing strain were considerably increased compared to those in the S228C strain. Analysis of ATP balance also showed that a larger amount of excess ATP was produced in the Kyokai 6 strain because of increased oxidative phosphorylation. These results suggest that high SAM production in Kyokai 6 strains could be attributed to enhanced ATP regeneration with high TCA cycle fluxes and respiration activity. Thus, maintaining high respiration efficiency during cultivation is important for improving SAM production. Copyright © 2015 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

  14. Modelling of the metabolism of Zymomonas mobilis

    Energy Technology Data Exchange (ETDEWEB)

    Posten, C; Thoma, M

    1986-01-01

    In order to optimize fermentations with respect to media, reactor configuration, and control a structured model of the metabolism of Zymononas mobilis has been developed. The model is based on structure of metabolism, rate limiting steps, energy balance and metabolic elemental balances. A three-fold effect of ethanol has been observed concerning substrate-turnover, ammonia uptake and energy consumption. In addition to the metabolic view a structured cell-membrane-model should be considered.

  15. Validating modeled turbulent heat fluxes across large freshwater surfaces

    Science.gov (United States)

    Lofgren, B. M.; Fujisaki-Manome, A.; Gronewold, A.; Anderson, E. J.; Fitzpatrick, L.; Blanken, P.; Spence, C.; Lenters, J. D.; Xiao, C.; Charusambot, U.

    2017-12-01

    Turbulent fluxes of latent and sensible heat are important physical processes that influence the energy and water budgets of the Great Lakes. Validation and improvement of bulk flux algorithms to simulate these turbulent heat fluxes are critical for accurate prediction of hydrodynamics, water levels, weather, and climate over the region. Here we consider five heat flux algorithms from several model systems; the Finite-Volume Community Ocean Model, the Weather Research and Forecasting model, and the Large Lake Thermodynamics Model, which are used in research and operational environments and concentrate on different aspects of the Great Lakes' physical system, but interface at the lake surface. The heat flux algorithms were isolated from each model and driven by meteorological data from over-lake stations in the Great Lakes Evaporation Network. The simulation results were compared with eddy covariance flux measurements at the same stations. All models show the capacity to the seasonal cycle of the turbulent heat fluxes. Overall, the Coupled Ocean Atmosphere Response Experiment algorithm in FVCOM has the best agreement with eddy covariance measurements. Simulations with the other four algorithms are overall improved by updating the parameterization of roughness length scales of temperature and humidity. Agreement between modelled and observed fluxes notably varied with geographical locations of the stations. For example, at the Long Point station in Lake Erie, observed fluxes are likely influenced by the upwind land surface while the simulations do not take account of the land surface influence, and therefore the agreement is worse in general.

  16. Testicular Metabolic Reprogramming in Neonatal Streptozotocin-Induced Type 2 Diabetic Rats Impairs Glycolytic Flux and Promotes Glycogen Synthesis

    Science.gov (United States)

    Rato, L.; Alves, M. G.; Dias, T. R.; Cavaco, J. E.; Oliveira, Pedro F.

    2015-01-01

    Defects in testicular metabolism are directly implicated with male infertility, but most of the mechanisms associated with type 2 diabetes- (T2DM) induced male infertility remain unknown. We aimed to evaluate the effects of T2DM on testicular glucose metabolism by using a neonatal-streptozotocin- (n-STZ) T2DM animal model. Plasma and testicular hormonal levels were evaluated using specific kits. mRNA and protein expression levels were assessed by real-time PCR and Western Blot, respectively. Testicular metabolic profile was assessed by 1H-NMR spectroscopy. T2DM rats showed increased glycemic levels, impaired glucose tolerance and hyperinsulinemia. Both testicular and serum testosterone levels were decreased, whereas those of 17β-estradiol were not altered. Testicular glycolytic flux was not favored in testicles of T2DM rats, since, despite the increased expression of both glucose transporters 1 and 3 and the enzyme phosphofructokinase 1, lactate dehydrogenase activity was severely decreased contributing to lower testicular lactate content. However, T2DM enhanced testicular glycogen accumulation, by modulating the availability of the precursors for its synthesis. T2DM also affected the reproductive sperm parameters. Taken together these results indicate that T2DM is able to reprogram testicular metabolism by enhancing alternative metabolic pathways, particularly glycogen synthesis, and such alterations are associated with impaired sperm parameters. PMID:26064993

  17. Computational Flux Balance Analysis Predicts that Stimulation of Energy Metabolism in Astrocytes and their Metabolic Interactions with Neurons Depend on Uptake of K+ Rather than Glutamate.

    Science.gov (United States)

    DiNuzzo, Mauro; Giove, Federico; Maraviglia, Bruno; Mangia, Silvia

    2017-01-01

    Brain activity involves essential functional and metabolic interactions between neurons and astrocytes. The importance of astrocytic functions to neuronal signaling is supported by many experiments reporting high rates of energy consumption and oxidative metabolism in these glial cells. In the brain, almost all energy is consumed by the Na + /K + ATPase, which hydrolyzes 1 ATP to move 3 Na + outside and 2 K + inside the cells. Astrocytes are commonly thought to be primarily involved in transmitter glutamate cycling, a mechanism that however only accounts for few % of brain energy utilization. In order to examine the participation of astrocytic energy metabolism in brain ion homeostasis, here we attempted to devise a simple stoichiometric relation linking glutamatergic neurotransmission to Na + and K + ionic currents. To this end, we took into account ion pumps and voltage/ligand-gated channels using the stoichiometry derived from available energy budget for neocortical signaling and incorporated this stoichiometric relation into a computational metabolic model of neuron-astrocyte interactions. We aimed at reproducing the experimental observations about rates of metabolic pathways obtained by 13 C-NMR spectroscopy in rodent brain. When simulated data matched experiments as well as biophysical calculations, the stoichiometry for voltage/ligand-gated Na + and K + fluxes generated by neuronal activity was close to a 1:1 relationship, and specifically 63/58 Na + /K + ions per glutamate released. We found that astrocytes are stimulated by the extracellular K + exiting neurons in excess of the 3/2 Na + /K + ratio underlying Na + /K + ATPase-catalyzed reaction. Analysis of correlations between neuronal and astrocytic processes indicated that astrocytic K + uptake, but not astrocytic Na + -coupled glutamate uptake, is instrumental for the establishment of neuron-astrocytic metabolic partnership. Our results emphasize the importance of K + in stimulating the activation of

  18. Assessment of energetic costs of AhR activation by β-naphthoflavone in rainbow trout (Oncorhynchus mykiss) hepatocytes using metabolic flux analysis

    International Nuclear Information System (INIS)

    Nault, Rance; Abdul-Fattah, Hiba; Mironov, Gleb G.; Berezovski, Maxim V.; Moon, Thomas W.

    2013-01-01

    Exposure to environmental contaminants such as activators of the aryl hydrocarbon receptor (AhR) leads to the induction of defense and detoxification mechanisms. While these mechanisms allow organisms to metabolize and excrete at least some of these environmental contaminants, it has been proposed that these mechanisms lead to significant energetic challenges. This study tests the hypothesis that activation of the AhR by the model agonist β-naphthoflavone (βNF) results in increased energetic costs in rainbow trout (Oncorhynchus mykiss) hepatocytes. To address this hypothesis, we employed traditional biochemical approaches to examine energy allocation and metabolism including the adenylate energy charge (AEC), protein synthesis rates, Na + /K + -ATPase activity, and enzyme activities. Moreover, we have used for the first time in a fish cell preparation, metabolic flux analysis (MFA) an in silico approach for the estimation of intracellular metabolic fluxes. Exposure of trout hepatocytes to 1 μM βNF for 48 h did not alter hepatocyte AEC, protein synthesis, or Na + /K + -ATPase activity but did lead to sparing of glycogen reserves and changes in activities of alanine aminotransferase and citrate synthase suggesting altered metabolism. Conversely, MFA did not identify altered metabolic fluxes, although we do show that the dynamic metabolism of isolated trout hepatocytes poses a significant challenge for this type of approach which should be considered in future studies. - Highlights: • Energetic costs of AhR activation by βNF was examined in rainbow trout hepatocytes. • Metabolic flux analysis was performed on a fish cell preparation for the first time. • Exposure to βNF led to sparing of glycogen reserves and altered enzyme activities. • Adenylate energy charge was maintained despite temporal changes in metabolism

  19. Assessment of energetic costs of AhR activation by β-naphthoflavone in rainbow trout (Oncorhynchus mykiss) hepatocytes using metabolic flux analysis

    Energy Technology Data Exchange (ETDEWEB)

    Nault, Rance, E-mail: naultran@msu.edu [Ottawa-Carleton Institute of Biology, Department of Biology and Centre for Advanced Research in Environmental Genomics, University of Ottawa, Ottawa, Ontario, K1N 6N5 (Canada); Abdul-Fattah, Hiba [Ottawa-Carleton Institute of Biology, Department of Biology and Centre for Advanced Research in Environmental Genomics, University of Ottawa, Ottawa, Ontario, K1N 6N5 (Canada); Mironov, Gleb G.; Berezovski, Maxim V. [Ottawa-Carleton Institute of Biology, Department of Biology and Centre for Advanced Research in Environmental Genomics, University of Ottawa, Ottawa, Ontario, K1N 6N5 (Canada); Department of Chemistry, University of Ottawa, Ottawa, Ontario, K1N 6N5 (Canada); Moon, Thomas W. [Ottawa-Carleton Institute of Biology, Department of Biology and Centre for Advanced Research in Environmental Genomics, University of Ottawa, Ottawa, Ontario, K1N 6N5 (Canada)

    2013-08-15

    Exposure to environmental contaminants such as activators of the aryl hydrocarbon receptor (AhR) leads to the induction of defense and detoxification mechanisms. While these mechanisms allow organisms to metabolize and excrete at least some of these environmental contaminants, it has been proposed that these mechanisms lead to significant energetic challenges. This study tests the hypothesis that activation of the AhR by the model agonist β-naphthoflavone (βNF) results in increased energetic costs in rainbow trout (Oncorhynchus mykiss) hepatocytes. To address this hypothesis, we employed traditional biochemical approaches to examine energy allocation and metabolism including the adenylate energy charge (AEC), protein synthesis rates, Na{sup +}/K{sup +}-ATPase activity, and enzyme activities. Moreover, we have used for the first time in a fish cell preparation, metabolic flux analysis (MFA) an in silico approach for the estimation of intracellular metabolic fluxes. Exposure of trout hepatocytes to 1 μM βNF for 48 h did not alter hepatocyte AEC, protein synthesis, or Na{sup +}/K{sup +}-ATPase activity but did lead to sparing of glycogen reserves and changes in activities of alanine aminotransferase and citrate synthase suggesting altered metabolism. Conversely, MFA did not identify altered metabolic fluxes, although we do show that the dynamic metabolism of isolated trout hepatocytes poses a significant challenge for this type of approach which should be considered in future studies. - Highlights: • Energetic costs of AhR activation by βNF was examined in rainbow trout hepatocytes. • Metabolic flux analysis was performed on a fish cell preparation for the first time. • Exposure to βNF led to sparing of glycogen reserves and altered enzyme activities. • Adenylate energy charge was maintained despite temporal changes in metabolism.

  20. Metabolic flux profiling of MDCK cells during growth and canine adenovirus vector production.

    Science.gov (United States)

    Carinhas, Nuno; Pais, Daniel A M; Koshkin, Alexey; Fernandes, Paulo; Coroadinha, Ana S; Carrondo, Manuel J T; Alves, Paula M; Teixeira, Ana P

    2016-03-23

    Canine adenovirus vector type 2 (CAV2) represents an alternative to human adenovirus vectors for certain gene therapy applications, particularly neurodegenerative diseases. However, more efficient production processes, assisted by a greater understanding of the effect of infection on producer cells, are required. Combining [1,2-(13)C]glucose and [U-(13)C]glutamine, we apply for the first time (13)C-Metabolic flux analysis ((13)C-MFA) to study E1-transformed Madin-Darby Canine Kidney (MDCK) cells metabolism during growth and CAV2 production. MDCK cells displayed a marked glycolytic and ammoniagenic metabolism, and (13)C data revealed a large fraction of glutamine-derived labelling in TCA cycle intermediates, emphasizing the role of glutamine anaplerosis. (13)C-MFA demonstrated the importance of pyruvate cycling in balancing glycolytic and TCA cycle activities, as well as occurrence of reductive alphaketoglutarate (AKG) carboxylation. By turn, CAV2 infection significantly upregulated fluxes through most central metabolism, including glycolysis, pentose-phosphate pathway, glutamine anaplerosis and, more prominently, reductive AKG carboxylation and cytosolic acetyl-coenzyme A formation, suggestive of increased lipogenesis. Based on these results, we suggest culture supplementation strategies to stimulate nucleic acid and lipid biosynthesis for improved canine adenoviral vector production.

  1. Mapping cancer cell metabolism with 13 C flux analysis: Recent progress and future challenges

    Directory of Open Access Journals (Sweden)

    Casey Scott Duckwall

    2013-01-01

    Full Text Available The reprogramming of energy metabolism is emerging as an important molecular hallmark of cancer cells. Recent discoveries linking specific metabolic alterations to cancer development have strengthened the idea that altered metabolism is more than a side effect of malignant transformation, but may in fact be a functional driver of tumor growth and progression in some cancers. As a result, dysregulated metabolic pathways have become attractive targets for cancer therapeutics. This review highlights the application of 13 C metabolic flux analysis (MFA to map the flow of carbon through intracellular biochemical pathways of cancer cells. We summarize several recent applications of MFA that have identified novel biosynthetic pathways involved in cancer cell proliferation and shed light on the role of specific oncogenes in regulating these pathways. Through such studies, it has become apparent that the metabolic phenotypes of cancer cells are not as homogeneous as once thought, but instead depend strongly on the molecular alterations and environmental factors at play in each case.

  2. Squeezing Flux Out of Fat

    DEFF Research Database (Denmark)

    Gonzalez-Franquesa, Alba; Patti, Mary-Elizabeth

    2018-01-01

    Merging transcriptomics or metabolomics data remains insufficient for metabolic flux estimation. Ramirez et al. integrate a genome-scale metabolic model with extracellular flux data to predict and validate metabolic differences between white and brown adipose tissue. This method allows both metab...

  3. Concepts, challenges, and successes in modeling thermodynamics of metabolism.

    Science.gov (United States)

    Cannon, William R

    2014-01-01

    The modeling of the chemical reactions involved in metabolism is a daunting task. Ideally, the modeling of metabolism would use kinetic simulations, but these simulations require knowledge of the thousands of rate constants involved in the reactions. The measurement of rate constants is very labor intensive, and hence rate constants for most enzymatic reactions are not available. Consequently, constraint-based flux modeling has been the method of choice because it does not require the use of the rate constants of the law of mass action. However, this convenience also limits the predictive power of constraint-based approaches in that the law of mass action is used only as a constraint, making it difficult to predict metabolite levels or energy requirements of pathways. An alternative to both of these approaches is to model metabolism using simulations of states rather than simulations of reactions, in which the state is defined as the set of all metabolite counts or concentrations. While kinetic simulations model reactions based on the likelihood of the reaction derived from the law of mass action, states are modeled based on likelihood ratios of mass action. Both approaches provide information on the energy requirements of metabolic reactions and pathways. However, modeling states rather than reactions has the advantage that the parameters needed to model states (chemical potentials) are much easier to determine than the parameters needed to model reactions (rate constants). Herein, we discuss recent results, assumptions, and issues in using simulations of state to model metabolism.

  4. The nutritional status of Methanosarcina acetivorans regulates glycogen metabolism and gluconeogenesis and glycolysis fluxes.

    Science.gov (United States)

    Santiago-Martínez, Michel Geovanni; Encalada, Rusely; Lira-Silva, Elizabeth; Pineda, Erika; Gallardo-Pérez, Juan Carlos; Reyes-García, Marco Antonio; Saavedra, Emma; Moreno-Sánchez, Rafael; Marín-Hernández, Alvaro; Jasso-Chávez, Ricardo

    2016-05-01

    Gluconeogenesis is an essential pathway in methanogens because they are unable to use exogenous hexoses as carbon source for cell growth. With the aim of understanding the regulatory mechanisms of central carbon metabolism in Methanosarcina acetivorans, the present study investigated gene expression, the activities and metabolic regulation of key enzymes, metabolite contents and fluxes of gluconeogenesis, as well as glycolysis and glycogen synthesis/degradation pathways. Cells were grown with methanol as a carbon source. Key enzymes were kinetically characterized at physiological pH/temperature. Active consumption of methanol during exponential cell growth correlated with significant methanogenesis, gluconeogenic flux and steady glycogen synthesis. After methanol exhaustion, cells reached the stationary growth phase, which correlated with the rise in glycogen consumption and glycolytic flux, decreased methanogenesis, negligible acetate production and an absence of gluconeogenesis. Elevated activities of carbon monoxide dehydrogenase/acetyl-CoA synthetase complex and pyruvate: ferredoxin oxidoreductase suggested the generation of acetyl-CoA and pyruvate for glycogen synthesis. In the early stationary growth phase, the transcript contents and activities of pyruvate phosphate dikinase, fructose 1,6-bisphosphatase and glycogen synthase decreased, whereas those of glycogen phosphorylase, ADP-phosphofructokinase and pyruvate kinase increased. Therefore, glycogen and gluconeogenic metabolites were synthesized when an external carbon source was provided. Once such a carbon source became depleted, glycolysis and methanogenesis fed by glycogen degradation provided the ATP supply. Weak inhibition of key enzymes by metabolites suggested that the pathways evaluated were mainly transcriptionally regulated. Because glycogen metabolism and glycolysis/gluconeogenesis are not present in all methanogens, the overall data suggest that glycogen storage might represent an environmental

  5. Generalized flux states of the t-J model

    International Nuclear Information System (INIS)

    Nori, F.; Abrahams, E.; Zimanyi, G.T.

    1990-01-01

    We investigate certain generalized flux phases arising in a mean-field approach to the t-J model. First, we establish that the energy of noninteracting electrons moving in a uniform magnetic field has an absolute minimum as a function of the flux at exactly one flux quantum per particle. Using this result, we show that if the hard-core nature of the hole bosons is taken into account, then the slave-boson mean-field approximation for the t-J Hamiltonian allows for a solution where both the spinons and the holons experience an average flux of one flux quantum per particle. This enables them to achieve the lowest possible energy within the manifold of spatially uniform flux states. In the case of the continuum model, this is possible only for certain fractional fillings and we speculate that the system may react to this frustration effect by phase separation

  6. A procedure for the estimation over time of metabolic fluxes in scenarios where measurements are uncertain and/or insufficient

    Directory of Open Access Journals (Sweden)

    Picó Jesús

    2007-10-01

    Full Text Available Abstract Background An indirect approach is usually used to estimate the metabolic fluxes of an organism: couple the available measurements with known biological constraints (e.g. stoichiometry. Typically this estimation is done under a static point of view. Therefore, the fluxes so obtained are only valid while the environmental conditions and the cell state remain stable. However, estimating the evolution over time of the metabolic fluxes is valuable to investigate the dynamic behaviour of an organism and also to monitor industrial processes. Although Metabolic Flux Analysis can be successively applied with this aim, this approach has two drawbacks: i sometimes it cannot be used because there is a lack of measurable fluxes, and ii the uncertainty of experimental measurements cannot be considered. The Flux Balance Analysis could be used instead, but the assumption of optimal behaviour of the organism brings other difficulties. Results We propose a procedure to estimate the evolution of the metabolic fluxes that is structured as follows: 1 measure the concentrations of extracellular species and biomass, 2 convert this data to measured fluxes and 3 estimate the non-measured fluxes using the Flux Spectrum Approach, a variant of Metabolic Flux Analysis that overcomes the difficulties mentioned above without assuming optimal behaviour. We apply the procedure to a real problem taken from the literature: estimate the metabolic fluxes during a cultivation of CHO cells in batch mode. We show that it provides a reliable and rich estimation of the non-measured fluxes, thanks to considering measurements uncertainty and reversibility constraints. We also demonstrate that this procedure can estimate the non-measured fluxes even when there is a lack of measurable species. In addition, it offers a new method to deal with inconsistency. Conclusion This work introduces a procedure to estimate time-varying metabolic fluxes that copes with the insufficiency of

  7. Inverse modeling of the terrestrial carbon flux in China with flux covariance among inverted regions

    Science.gov (United States)

    Wang, H.; Jiang, F.; Chen, J. M.; Ju, W.; Wang, H.

    2011-12-01

    Quantitative understanding of the role of ocean and terrestrial biosphere in the global carbon cycle, their response and feedback to climate change is required for the future projection of the global climate. China has the largest amount of anthropogenic CO2 emission, diverse terrestrial ecosystems and an unprecedented rate of urbanization. Thus information on spatial and temporal distributions of the terrestrial carbon flux in China is of great importance in understanding the global carbon cycle. We developed a nested inversion with focus in China. Based on Transcom 22 regions for the globe, we divide China and its neighboring countries into 17 regions, making 39 regions in total for the globe. A Bayesian synthesis inversion is made to estimate the terrestrial carbon flux based on GlobalView CO2 data. In the inversion, GEOS-Chem is used as the transport model to develop the transport matrix. A terrestrial ecosystem model named BEPS is used to produce the prior surface flux to constrain the inversion. However, the sparseness of available observation stations in Asia poses a challenge to the inversion for the 17 small regions. To obtain additional constraint on the inversion, a prior flux covariance matrix is constructed using the BEPS model through analyzing the correlation in the net carbon flux among regions under variable climate conditions. The use of the covariance among different regions in the inversion effectively extends the information content of CO2 observations to more regions. The carbon flux over the 39 land and ocean regions are inverted for the period from 2004 to 2009. In order to investigate the impact of introducing the covariance matrix with non-zero off-diagonal values to the inversion, the inverted terrestrial carbon flux over China is evaluated against ChinaFlux eddy-covariance observations after applying an upscaling methodology.

  8. Flux-limited diffusion models in radiation hydrodynamics

    International Nuclear Information System (INIS)

    Pomraning, G.C.; Szilard, R.H.

    1993-01-01

    The authors discuss certain flux-limited diffusion theories which approximately describe radiative transfer in the presence of steep spatial gradients. A new formulation is presented which generalizes a flux-limited description currently in widespread use for large radiation hydrodynamic calculations. This new formation allows more than one Case discrete mode to be described by a flux-limited diffusion equation. Such behavior is not extant in existing formulations. Numerical results predicted by these flux-limited diffusion models are presented for radiation penetration into an initially cold halfspace. 37 refs., 5 figs

  9. Construction of a Genome-Scale Metabolic Model of Arthrospira platensis NIES-39 and Metabolic Design for Cyanobacterial Bioproduction.

    Directory of Open Access Journals (Sweden)

    Katsunori Yoshikawa

    Full Text Available Arthrospira (Spirulina platensis is a promising feedstock and host strain for bioproduction because of its high accumulation of glycogen and superior characteristics for industrial production. Metabolic simulation using a genome-scale metabolic model and flux balance analysis is a powerful method that can be used to design metabolic engineering strategies for the improvement of target molecule production. In this study, we constructed a genome-scale metabolic model of A. platensis NIES-39 including 746 metabolic reactions and 673 metabolites, and developed novel strategies to improve the production of valuable metabolites, such as glycogen and ethanol. The simulation results obtained using the metabolic model showed high consistency with experimental results for growth rates under several trophic conditions and growth capabilities on various organic substrates. The metabolic model was further applied to design a metabolic network to improve the autotrophic production of glycogen and ethanol. Decreased flux of reactions related to the TCA cycle and phosphoenolpyruvate reaction were found to improve glycogen production. Furthermore, in silico knockout simulation indicated that deletion of genes related to the respiratory chain, such as NAD(PH dehydrogenase and cytochrome-c oxidase, could enhance ethanol production by using ammonium as a nitrogen source.

  10. (13)C-metabolic flux analysis of lipid accumulation in the oleaginous fungus Mucor circinelloides.

    Science.gov (United States)

    Zhao, Lina; Zhang, Huaiyuan; Wang, Liping; Chen, Haiqin; Chen, Yong Q; Chen, Wei; Song, Yuanda

    2015-12-01

    The oleaginous fungus Mucor circinelloides is of industrial interest because it can produce high levels of polyunsaturated fatty acid γ-linolenic acid. M. circinelloides CBS 277.49 is able to accumulate less than 15% of cell dry weight as lipids, while M. circinelloides WJ11 can accumulate lipid up to 36%. In order to better understand the mechanisms behind the differential lipid accumulation in these two strains, tracer experiments with (13)C-glucose were performed with the growth of M. circinelloides and subsequent gas chromatography-mass spectrometric detection of (13)C-patterns in proteinogenic amino acids was carried out to identify the metabolic network topology and estimate intracellular fluxes. Our results showed that the high oleaginous strain WJ11 had higher flux of pentose phosphate pathway and malic enzyme, lower flux in tricarboxylic acid cycle, higher flux in glyoxylate cycle and ATP: citrate lyase, together, it might provide more NADPH and substrate acetyl-CoA for fatty acid synthesis. Copyright © 2015 Elsevier Ltd. All rights reserved.

  11. iMS2Flux – a high–throughput processing tool for stable isotope labeled mass spectrometric data used for metabolic flux analysis

    Directory of Open Access Journals (Sweden)

    Poskar C Hart

    2012-11-01

    Full Text Available Abstract Background Metabolic flux analysis has become an established method in systems biology and functional genomics. The most common approach for determining intracellular metabolic fluxes is to utilize mass spectrometry in combination with stable isotope labeling experiments. However, before the mass spectrometric data can be used it has to be corrected for biases caused by naturally occurring stable isotopes, by the analytical technique(s employed, or by the biological sample itself. Finally the MS data and the labeling information it contains have to be assembled into a data format usable by flux analysis software (of which several dedicated packages exist. Currently the processing of mass spectrometric data is time-consuming and error-prone requiring peak by peak cut-and-paste analysis and manual curation. In order to facilitate high-throughput metabolic flux analysis, the automation of multiple steps in the analytical workflow is necessary. Results Here we describe iMS2Flux, software developed to automate, standardize and connect the data flow between mass spectrometric measurements and flux analysis programs. This tool streamlines the transfer of data from extraction via correction tools to 13C-Flux software by processing MS data from stable isotope labeling experiments. It allows the correction of large and heterogeneous MS datasets for the presence of naturally occurring stable isotopes, initial biomass and several mass spectrometry effects. Before and after data correction, several checks can be performed to ensure accurate data. The corrected data may be returned in a variety of formats including those used by metabolic flux analysis software such as 13CFLUX, OpenFLUX and 13CFLUX2. Conclusion iMS2Flux is a versatile, easy to use tool for the automated processing of mass spectrometric data containing isotope labeling information. It represents the core framework for a standardized workflow and data processing. Due to its flexibility

  12. Metabolic flux profiling of MDCK cells during growth and canine adenovirus vector production

    OpenAIRE

    Nuno Carinhas; Daniel A. M. Pais; Alexey Koshkin; Paulo Fernandes; Ana S. Coroadinha; Manuel J. T. Carrondo; Paula M. Alves; Ana P. Teixeira

    2016-01-01

    Canine adenovirus vector type 2 (CAV2) represents an alternative to human adenovirus vectors for certain gene therapy applications, particularly neurodegenerative diseases. However, more efficient production processes, assisted by a greater understanding of the effect of infection on producer cells, are required. Combining [1,2-13C]glucose and [U-13C]glutamine, we apply for the first time 13C-Metabolic flux analysis (13C-MFA) to study E1-transformed Madin-Darby Canine Kidney (MDCK) cells meta...

  13. OptFlux: an open-source software platform for in silico metabolic engineering

    DEFF Research Database (Denmark)

    Rocha, I.; Maia, P.; Evangelista, P.

    2010-01-01

    to address industrial goals. However, the use of these methods has been restricted to bioinformaticians or other expert researchers. The main aim of this work is, therefore, to provide a user-friendly computational tool for Metabolic Engineering applications. Results: OptFlux is an open-source and modular...... available a number of useful tools. Its open-source nature invites contributions by all those interested in making their methods available for the community. Given its plug-in based architecture it can be extended with new functionalities. Currently, several plug-ins are being developed, including network...

  14. Multi-objective experimental design for (13)C-based metabolic flux analysis.

    Science.gov (United States)

    Bouvin, Jeroen; Cajot, Simon; D'Huys, Pieter-Jan; Ampofo-Asiama, Jerry; Anné, Jozef; Van Impe, Jan; Geeraerd, Annemie; Bernaerts, Kristel

    2015-10-01

    (13)C-based metabolic flux analysis is an excellent technique to resolve fluxes in the central carbon metabolism but costs can be significant when using specialized tracers. This work presents a framework for cost-effective design of (13)C-tracer experiments, illustrated on two different networks. Linear and non-linear optimal input mixtures are computed for networks for Streptomyces lividans and a carcinoma cell line. If only glucose tracers are considered as labeled substrate for a carcinoma cell line or S. lividans, the best parameter estimation accuracy is obtained by mixtures containing high amounts of 1,2-(13)C2 glucose combined with uniformly labeled glucose. Experimental designs are evaluated based on a linear (D-criterion) and non-linear approach (S-criterion). Both approaches generate almost the same input mixture, however, the linear approach is favored due to its low computational effort. The high amount of 1,2-(13)C2 glucose in the optimal designs coincides with a high experimental cost, which is further enhanced when labeling is introduced in glutamine and aspartate tracers. Multi-objective optimization gives the possibility to assess experimental quality and cost at the same time and can reveal excellent compromise experiments. For example, the combination of 100% 1,2-(13)C2 glucose with 100% position one labeled glutamine and the combination of 100% 1,2-(13)C2 glucose with 100% uniformly labeled glutamine perform equally well for the carcinoma cell line, but the first mixture offers a decrease in cost of $ 120 per ml-scale cell culture experiment. We demonstrated the validity of a multi-objective linear approach to perform optimal experimental designs for the non-linear problem of (13)C-metabolic flux analysis. Tools and a workflow are provided to perform multi-objective design. The effortless calculation of the D-criterion can be exploited to perform high-throughput screening of possible (13)C-tracers, while the illustrated benefit of multi

  15. Random sampling of elementary flux modes in large-scale metabolic networks.

    Science.gov (United States)

    Machado, Daniel; Soons, Zita; Patil, Kiran Raosaheb; Ferreira, Eugénio C; Rocha, Isabel

    2012-09-15

    The description of a metabolic network in terms of elementary (flux) modes (EMs) provides an important framework for metabolic pathway analysis. However, their application to large networks has been hampered by the combinatorial explosion in the number of modes. In this work, we develop a method for generating random samples of EMs without computing the whole set. Our algorithm is an adaptation of the canonical basis approach, where we add an additional filtering step which, at each iteration, selects a random subset of the new combinations of modes. In order to obtain an unbiased sample, all candidates are assigned the same probability of getting selected. This approach avoids the exponential growth of the number of modes during computation, thus generating a random sample of the complete set of EMs within reasonable time. We generated samples of different sizes for a metabolic network of Escherichia coli, and observed that they preserve several properties of the full EM set. It is also shown that EM sampling can be used for rational strain design. A well distributed sample, that is representative of the complete set of EMs, should be suitable to most EM-based methods for analysis and optimization of metabolic networks. Source code for a cross-platform implementation in Python is freely available at http://code.google.com/p/emsampler. dmachado@deb.uminho.pt Supplementary data are available at Bioinformatics online.

  16. Integrated stoichiometric, thermodynamic and kinetic modelling of steady state metabolism.

    Science.gov (United States)

    Fleming, R M T; Thiele, I; Provan, G; Nasheuer, H P

    2010-06-07

    The quantitative analysis of biochemical reactions and metabolites is at frontier of biological sciences. The recent availability of high-throughput technology data sets in biology has paved the way for new modelling approaches at various levels of complexity including the metabolome of a cell or an organism. Understanding the metabolism of a single cell and multi-cell organism will provide the knowledge for the rational design of growth conditions to produce commercially valuable reagents in biotechnology. Here, we demonstrate how equations representing steady state mass conservation, energy conservation, the second law of thermodynamics, and reversible enzyme kinetics can be formulated as a single system of linear equalities and inequalities, in addition to linear equalities on exponential variables. Even though the feasible set is non-convex, the reformulation is exact and amenable to large-scale numerical analysis, a prerequisite for computationally feasible genome scale modelling. Integrating flux, concentration and kinetic variables in a unified constraint-based formulation is aimed at increasing the quantitative predictive capacity of flux balance analysis. Incorporation of experimental and theoretical bounds on thermodynamic and kinetic variables ensures that the predicted steady state fluxes are both thermodynamically and biochemically feasible. The resulting in silico predictions are tested against fluxomic data for central metabolism in Escherichia coli and compare favourably with in silico prediction by flux balance analysis. Copyright (c) 2010 Elsevier Ltd. All rights reserved.

  17. Modeling and prototyping of a flux concentrator for positron capture

    International Nuclear Information System (INIS)

    Liu, W.; Gai, W.; Wang, H.; Wong, T.

    2008-01-01

    An adiabatic matching device (AMD) generates a tapered high-strength magnetic field to capture positrons emitted from a positron target to a downstream accelerating structure. The AMD is a key component of a positron source and represents a technical challenge. The International Linear Collider collaboration is proposing to employ a pulsed, normal-conducting, flux-concentrator to generate a 5 Tesla initial magnetic field. The flux-concentrator structure itself and the interactions between the flux-concentrator and the external power supply circuits give rise to a nontrivial system. In this paper, we present a recently developed equivalent circuit model for a flux concentrator, along with the characteristics of a prototype fabricated for validating the model. Using the model, we can obtain the transient response of the pulsed magnetic field and the field profile. Calculations based on the model and the results of measurements made on the prototype are in good agreement.

  18. Modeling of Drift Effects on Solar Tower Concentrated Flux Distributions

    Directory of Open Access Journals (Sweden)

    Luis O. Lara-Cerecedo

    2016-01-01

    Full Text Available A novel modeling tool for calculation of central receiver concentrated flux distributions is presented, which takes into account drift effects. This tool is based on a drift model that includes different geometrical error sources in a rigorous manner and on a simple analytic approximation for the individual flux distribution of a heliostat. The model is applied to a group of heliostats of a real field to obtain the resulting flux distribution and its variation along the day. The distributions differ strongly from those obtained assuming the ideal case without drift or a case with a Gaussian tracking error function. The time evolution of peak flux is also calculated to demonstrate the capabilities of the model. The evolution of this parameter also shows strong differences in comparison to the case without drift.

  19. Meridional Flow Observations: Implications for the current Flux Transport Models

    International Nuclear Information System (INIS)

    Gonzalez Hernandez, Irene; Komm, Rudolf; Kholikov, Shukur; Howe, Rachel; Hill, Frank

    2011-01-01

    Meridional circulation has become a key element in the solar dynamo flux transport models. Available helioseismic observations from several instruments, Taiwan Oscillation Network (TON), Global Oscillation Network Group (GONG) and Michelson Doppler Imager (MDI), have made possible a continuous monitoring of the solar meridional flow in the subphotospheric layers for the last solar cycle, including the recent extended minimum. Here we review some of the meridional circulation observations using local helioseismology techniques and relate them to magnetic flux transport models.

  20. Bayesian modeling and prediction of solar particles flux

    International Nuclear Information System (INIS)

    Dedecius, Kamil; Kalova, Jana

    2010-01-01

    An autoregression model was developed based on the Bayesian approach. Considering the solar wind non-homogeneity, the idea was applied of combining the pure autoregressive properties of the model with expert knowledge based on a similar behaviour of the various phenomena related to the flux properties. Examples of such situations include the hardening of the X-ray spectrum, which is often followed by coronal mass ejection and a significant increase in the particles flux intensity

  1. Flux

    DEFF Research Database (Denmark)

    Ravn, Ib

    . FLUX betegner en flyden eller strømmen, dvs. dynamik. Forstår man livet som proces og udvikling i stedet for som ting og mekanik, får man et andet billede af det gode liv end det, som den velkendte vestlige mekanicisme lægger op til. Dynamisk forstået indebærer det gode liv den bedst mulige...... kanalisering af den flux eller energi, der strømmer igennem os og giver sig til kende i vore daglige aktiviteter. Skal vores tanker, handlinger, arbejde, samvær og politiske liv organiseres efter stramme og faste regelsæt, uden slinger i valsen? Eller skal de tværtimod forløbe ganske uhindret af regler og bånd...

  2. Evaluation of Deep Learning Models for Predicting CO2 Flux

    Science.gov (United States)

    Halem, M.; Nguyen, P.; Frankel, D.

    2017-12-01

    Artificial neural networks have been employed to calculate surface flux measurements from station data because they are able to fit highly nonlinear relations between input and output variables without knowing the detail relationships between the variables. However, the accuracy in performing neural net estimates of CO2 flux from observations of CO2 and other atmospheric variables is influenced by the architecture of the neural model, the availability, and complexity of interactions between physical variables such as wind, temperature, and indirect variables like latent heat, and sensible heat, etc. We evaluate two deep learning models, feed forward and recurrent neural network models to learn how they each respond to the physical measurements, time dependency of the measurements of CO2 concentration, humidity, pressure, temperature, wind speed etc. for predicting the CO2 flux. In this paper, we focus on a) building neural network models for estimating CO2 flux based on DOE data from tower Atmospheric Radiation Measurement data; b) evaluating the impact of choosing the surface variables and model hyper-parameters on the accuracy and predictions of surface flux; c) assessing the applicability of the neural network models on estimate CO2 flux by using OCO-2 satellite data; d) studying the efficiency of using GPU-acceleration for neural network performance using IBM Power AI deep learning software and packages on IBM Minsky system.

  3. Metabolic flux analysis of the hydrogen production potential in Synechocystis sp. PCC6803

    Energy Technology Data Exchange (ETDEWEB)

    Navarro, E. [Departamento de Lenguajes y Ciencias de la Computacion, Campus de Teatrinos, Universidad de Malaga, 29071 Malaga (Spain); Montagud, A.; Fernandez de Cordoba, P.; Urchueguia, J.F. [Instituto Universitario de Matematica Pura y Aplicada, Universidad Politecnica de Valencia, Camino de Vera 14, 46022 Valencia (Spain)

    2009-11-15

    Hydrogen is a promising energy vector; however, finding methods to produce it from renewable sources is essential to allow its wide-scale use. In that line, biological hydrogen production, although it is considered as a possible alternative, requires substantial improvements to overcome its present low yields. In that direction, genetic manipulation probably will play a central role and from that point of view metabolic flux analysis (MFA) constitutes an important tool to guide a priori most suitable genetic modifications oriented to a hydrogen yield increase. In this work MFA has been applied to analyze hydrogen photoproduction of Synechocystis sp. PCC6803. Flux analysis was carried out based on literature data and several basic fluxes were estimated in different growing conditions of the system. From this analysis, an upper limit for hydrogen photoproduction has been determined indicating a wide margin for improvement. MFA was also used to find a feasible operating space for hydrogen production, which avoids oxygen inhibition, one of the most important limitations to make hydrogen production cost effective. In addition, a set of biotechnological strategies are proposed that would be consistent with the performed mathematical analysis. (author)

  4. Metabolic flux ratio analysis and cell staining suggest the existence of C4 photosynthesis in Phaeodactylum tricornutum.

    Science.gov (United States)

    Huang, A; Liu, L; Zhao, P; Yang, C; Wang, G C

    2016-03-01

    Mechanisms for carbon fixation via photosynthesis in the diatom Phaeodactylum tricornutum Bohlin were studied recently but there remains a long-standing debate concerning the occurrence of C4 photosynthesis in this species. A thorough investigation of carbon metabolism and the evidence for C4 photosynthesis based on organelle partitioning was needed. In this study, we identified the flux ratios between C3 and C4 compounds in P. tricornutum using (13)C-labelling metabolic flux ratio analysis, and stained cells with various cell-permeant fluorescent probes to investigate the likely organelle partitioning required for single-cell C4 photosynthesis. Metabolic flux ratio analysis indicated the C3/C4 exchange ratios were high. Cell staining indicated organelle partitioning required for single-cell C4 photosynthesis might exist in P. tricornutum. The results of (13)C-labelling metabolic flux ratio analysis and cell staining suggest single-cell C4 photosynthesis exists in P. tricornutum. This study provides insights into photosynthesis patterns of P. tricornutum and the evidence for C4 photosynthesis based on (13)C-labelling metabolic flux ratio analysis and organelle partitioning. © 2015 The Society for Applied Microbiology.

  5. Thermodynamic principles governing metabolic operation : inference, analysis, and prediction

    NARCIS (Netherlands)

    Niebel, Bastian

    2015-01-01

    The principles governing metabolic flux are poorly understood. Because diverse organisms show similar metabolic flux patterns, we hypothesized that fundamental thermodynamic constraints might shape cellular metabolism. We developed a constraint-based model for Saccharomyces cerevisiae that included

  6. Metabolic Flux Analysis in Isotope Labeling Experiments Using the Adjoint Approach.

    Science.gov (United States)

    Mottelet, Stephane; Gaullier, Gil; Sadaka, Georges

    2017-01-01

    Comprehension of metabolic pathways is considerably enhanced by metabolic flux analysis (MFA-ILE) in isotope labeling experiments. The balance equations are given by hundreds of algebraic (stationary MFA) or ordinary differential equations (nonstationary MFA), and reducing the number of operations is therefore a crucial part of reducing the computation cost. The main bottleneck for deterministic algorithms is the computation of derivatives, particularly for nonstationary MFA. In this article, we explain how the overall identification process may be speeded up by using the adjoint approach to compute the gradient of the residual sum of squares. The proposed approach shows significant improvements in terms of complexity and computation time when it is compared with the usual (direct) approach. Numerical results are obtained for the central metabolic pathways of Escherichia coli and are validated against reference software in the stationary case. The methods and algorithms described in this paper are included in the sysmetab software package distributed under an Open Source license at http://forge.scilab.org/index.php/p/sysmetab/.

  7. Elliptic-cylindrical analytical flux-rope model for ICMEs

    Science.gov (United States)

    Nieves-Chinchilla, T.; Linton, M.; Hidalgo, M. A. U.; Vourlidas, A.

    2016-12-01

    We present an analytical flux-rope model for realistic magnetic structures embedded in Interplanetary Coronal Mass Ejections. The framework of this model was established by Nieves-Chinchilla et al. (2016) with the circular-cylindrical analytical flux rope model and under the concept developed by Hidalgo et al. (2002). Elliptic-cylindrical geometry establishes the first-grade of complexity of a series of models. The model attempts to describe the magnetic flux rope topology with distorted cross-section as a possible consequence of the interaction with the solar wind. In this model, the flux rope is completely described in the non-euclidean geometry. The Maxwell equations are solved using tensor calculus consistently with the geometry chosen, invariance along the axial component, and with the only assumption of no radial current density. The model is generalized in terms of the radial dependence of the poloidal current density component and axial current density component. The misalignment between current density and magnetic field is studied in detail for the individual cases of different pairs of indexes for the axial and poloidal current density components. This theoretical analysis provides a map of the force distribution inside of the flux-rope. The reconstruction technique has been adapted to the model and compared with in situ ICME set of events with different in situ signatures. The successful result is limited to some cases with clear in-situ signatures of distortion. However, the model adds a piece in the puzzle of the physical-analytical representation of these magnetic structures. Other effects such as axial curvature, expansion and/or interaction could be incorporated in the future to fully understand the magnetic structure. Finally, the mathematical formulation of this model opens the door to the next model: toroidal flux rope analytical model.

  8. Plant metabolic modeling: achieving new insight into metabolism and metabolic engineering.

    Science.gov (United States)

    Baghalian, Kambiz; Hajirezaei, Mohammad-Reza; Schreiber, Falk

    2014-10-01

    Models are used to represent aspects of the real world for specific purposes, and mathematical models have opened up new approaches in studying the behavior and complexity of biological systems. However, modeling is often time-consuming and requires significant computational resources for data development, data analysis, and simulation. Computational modeling has been successfully applied as an aid for metabolic engineering in microorganisms. But such model-based approaches have only recently been extended to plant metabolic engineering, mainly due to greater pathway complexity in plants and their highly compartmentalized cellular structure. Recent progress in plant systems biology and bioinformatics has begun to disentangle this complexity and facilitate the creation of efficient plant metabolic models. This review highlights several aspects of plant metabolic modeling in the context of understanding, predicting and modifying complex plant metabolism. We discuss opportunities for engineering photosynthetic carbon metabolism, sucrose synthesis, and the tricarboxylic acid cycle in leaves and oil synthesis in seeds and the application of metabolic modeling to the study of plant acclimation to the environment. The aim of the review is to offer a current perspective for plant biologists without requiring specialized knowledge of bioinformatics or systems biology. © 2014 American Society of Plant Biologists. All rights reserved.

  9. Mathematical model and simulations of radiation fluxes from buried radionuclides

    International Nuclear Information System (INIS)

    Ahmad Saat

    1999-01-01

    A mathematical model and a simple Monte Carlo simulations were developed to predict radiation fluxes from buried radionuclides. The model and simulations were applied to measured (experimental) data. The results of the mathematical model showed good acceptable order of magnitude agreement. A good agreement was also obtained between the simple simulations and the experimental results. Thus, knowing the radionuclide distribution profiles in soil from a core sample, it can be applied to the model or simulations to estimate the radiation fluxes emerging from the soil surface. (author)

  10. An optimization model for metabolic pathways.

    Science.gov (United States)

    Planes, F J; Beasley, J E

    2009-10-15

    Different mathematical methods have emerged in the post-genomic era to determine metabolic pathways. These methods can be divided into stoichiometric methods and path finding methods. In this paper we detail a novel optimization model, based upon integer linear programming, to determine metabolic pathways. Our model links reaction stoichiometry with path finding in a single approach. We test the ability of our model to determine 40 annotated Escherichia coli metabolic pathways. We show that our model is able to determine 36 of these 40 pathways in a computationally effective manner.

  11. A holistic view of dietary carbohydrate utilization in lobster: digestion, postprandial nutrient flux, and metabolism.

    Science.gov (United States)

    Rodríguez-Viera, Leandro; Perera, Erick; Casuso, Antonio; Perdomo-Morales, Rolando; Gutierrez, Odilia; Scull, Idania; Carrillo, Olimpia; Martos-Sitcha, Juan A; García-Galano, Tsai; Mancera, Juan Miguel

    2014-01-01

    Crustaceans exhibit a remarkable variation in their feeding habits and food type, but most knowledge on carbohydrate digestion and utilization in this group has come from research on few species. The aim of this study was to make an integrative analysis of dietary carbohydrate utilization in the spiny lobster Panulirus argus. We used complementary methodologies such as different assessments of digestibility, activity measurements of digestive and metabolic enzymes, and post-feeding flux of nutrients and metabolites. Several carbohydrates were well digested by the lobster, but maize starch was less digestible than all other starches studied, and its inclusion in diet affected protein digestibility. Most intense hydrolysis of carbohydrates in the gastric chamber of lobster occurred between 2-6 h after ingestion and afterwards free glucose increased in hemolymph. The inclusion of wheat in diet produced a slow clearance of glucose from the gastric fluid and a gradual increase in hemolymph glucose. More intense hydrolysis of protein in the gastric chamber occurred 6-12 h after ingestion and then amino acids tended to increase in hemolymph. Triglyceride concentration in hemolymph rose earlier in wheat-fed lobsters than in lobsters fed other carbohydrates, but it decreased the most 24 h later. Analyses of metabolite levels and activities of different metabolic enzymes revealed that intermolt lobsters had a low capacity to store and use glycogen, although it was slightly higher in wheat-fed lobsters. Lobsters fed maize and rice diets increased amino acid catabolism, while wheat-fed lobsters exhibited higher utilization of fatty acids. Multivariate analysis confirmed that the type of carbohydrate ingested had a profound effect on overall metabolism. Although we found no evidence of a protein-sparing effect of dietary carbohydrate, differences in the kinetics of their digestion and absorption impacted lobster metabolism determining the fate of other nutrients.

  12. A holistic view of dietary carbohydrate utilization in lobster: digestion, postprandial nutrient flux, and metabolism.

    Directory of Open Access Journals (Sweden)

    Leandro Rodríguez-Viera

    Full Text Available Crustaceans exhibit a remarkable variation in their feeding habits and food type, but most knowledge on carbohydrate digestion and utilization in this group has come from research on few species. The aim of this study was to make an integrative analysis of dietary carbohydrate utilization in the spiny lobster Panulirus argus. We used complementary methodologies such as different assessments of digestibility, activity measurements of digestive and metabolic enzymes, and post-feeding flux of nutrients and metabolites. Several carbohydrates were well digested by the lobster, but maize starch was less digestible than all other starches studied, and its inclusion in diet affected protein digestibility. Most intense hydrolysis of carbohydrates in the gastric chamber of lobster occurred between 2-6 h after ingestion and afterwards free glucose increased in hemolymph. The inclusion of wheat in diet produced a slow clearance of glucose from the gastric fluid and a gradual increase in hemolymph glucose. More intense hydrolysis of protein in the gastric chamber occurred 6-12 h after ingestion and then amino acids tended to increase in hemolymph. Triglyceride concentration in hemolymph rose earlier in wheat-fed lobsters than in lobsters fed other carbohydrates, but it decreased the most 24 h later. Analyses of metabolite levels and activities of different metabolic enzymes revealed that intermolt lobsters had a low capacity to store and use glycogen, although it was slightly higher in wheat-fed lobsters. Lobsters fed maize and rice diets increased amino acid catabolism, while wheat-fed lobsters exhibited higher utilization of fatty acids. Multivariate analysis confirmed that the type of carbohydrate ingested had a profound effect on overall metabolism. Although we found no evidence of a protein-sparing effect of dietary carbohydrate, differences in the kinetics of their digestion and absorption impacted lobster metabolism determining the fate of other

  13. Improving the phenotype predictions of a yeast genome-scale metabolic model by incorporating enzymatic constraints

    DEFF Research Database (Denmark)

    Sanchez, Benjamin J.; Zhang, Xi-Cheng; Nilsson, Avlant

    2017-01-01

    , which act as limitations on metabolic fluxes, are not taken into account. Here, we present GECKO, a method that enhances a GEM to account for enzymes as part of reactions, thereby ensuring that each metabolic flux does not exceed its maximum capacity, equal to the product of the enzyme's abundance...... and turnover number. We applied GECKO to a Saccharomyces cerevisiae GEM and demonstrated that the new model could correctly describe phenotypes that the previous model could not, particularly under high enzymatic pressure conditions, such as yeast growing on different carbon sources in excess, coping...... with stress, or overexpressing a specific pathway. GECKO also allows to directly integrate quantitative proteomics data; by doing so, we significantly reduced flux variability of the model, in over 60% of metabolic reactions. Additionally, the model gives insight into the distribution of enzyme usage between...

  14. DRUM: a new framework for metabolic modeling under non-balanced growth. Application to the carbon metabolism of unicellular microalgae.

    Science.gov (United States)

    Baroukh, Caroline; Muñoz-Tamayo, Rafael; Steyer, Jean-Philippe; Bernard, Olivier

    2014-01-01

    Metabolic modeling is a powerful tool to understand, predict and optimize bioprocesses, particularly when they imply intracellular molecules of interest. Unfortunately, the use of metabolic models for time varying metabolic fluxes is hampered by the lack of experimental data required to define and calibrate the kinetic reaction rates of the metabolic pathways. For this reason, metabolic models are often used under the balanced growth hypothesis. However, for some processes such as the photoautotrophic metabolism of microalgae, the balanced-growth assumption appears to be unreasonable because of the synchronization of their circadian cycle on the daily light. Yet, understanding microalgae metabolism is necessary to optimize the production yield of bioprocesses based on this microorganism, as for example production of third-generation biofuels. In this paper, we propose DRUM, a new dynamic metabolic modeling framework that handles the non-balanced growth condition and hence accumulation of intracellular metabolites. The first stage of the approach consists in splitting the metabolic network into sub-networks describing reactions which are spatially close, and which are assumed to satisfy balanced growth condition. The left metabolites interconnecting the sub-networks behave dynamically. Then, thanks to Elementary Flux Mode analysis, each sub-network is reduced to macroscopic reactions, for which simple kinetics are assumed. Finally, an Ordinary Differential Equation system is obtained to describe substrate consumption, biomass production, products excretion and accumulation of some internal metabolites. DRUM was applied to the accumulation of lipids and carbohydrates of the microalgae Tisochrysis lutea under day/night cycles. The resulting model describes accurately experimental data obtained in day/night conditions. It efficiently predicts the accumulation and consumption of lipids and carbohydrates.

  15. DRUM: a new framework for metabolic modeling under non-balanced growth. Application to the carbon metabolism of unicellular microalgae.

    Directory of Open Access Journals (Sweden)

    Caroline Baroukh

    Full Text Available Metabolic modeling is a powerful tool to understand, predict and optimize bioprocesses, particularly when they imply intracellular molecules of interest. Unfortunately, the use of metabolic models for time varying metabolic fluxes is hampered by the lack of experimental data required to define and calibrate the kinetic reaction rates of the metabolic pathways. For this reason, metabolic models are often used under the balanced growth hypothesis. However, for some processes such as the photoautotrophic metabolism of microalgae, the balanced-growth assumption appears to be unreasonable because of the synchronization of their circadian cycle on the daily light. Yet, understanding microalgae metabolism is necessary to optimize the production yield of bioprocesses based on this microorganism, as for example production of third-generation biofuels. In this paper, we propose DRUM, a new dynamic metabolic modeling framework that handles the non-balanced growth condition and hence accumulation of intracellular metabolites. The first stage of the approach consists in splitting the metabolic network into sub-networks describing reactions which are spatially close, and which are assumed to satisfy balanced growth condition. The left metabolites interconnecting the sub-networks behave dynamically. Then, thanks to Elementary Flux Mode analysis, each sub-network is reduced to macroscopic reactions, for which simple kinetics are assumed. Finally, an Ordinary Differential Equation system is obtained to describe substrate consumption, biomass production, products excretion and accumulation of some internal metabolites. DRUM was applied to the accumulation of lipids and carbohydrates of the microalgae Tisochrysis lutea under day/night cycles. The resulting model describes accurately experimental data obtained in day/night conditions. It efficiently predicts the accumulation and consumption of lipids and carbohydrates.

  16. Producing Acetic Acid of Acetobacter pasteurianus by Fermentation Characteristics and Metabolic Flux Analysis.

    Science.gov (United States)

    Wu, Xuefeng; Yao, Hongli; Liu, Qing; Zheng, Zhi; Cao, Lili; Mu, Dongdong; Wang, Hualin; Jiang, Shaotong; Li, Xingjiang

    2018-03-19

    The acetic acid bacterium Acetobacter pasteurianus plays an important role in acetic acid fermentation, which involves oxidation of ethanol to acetic acid through the ethanol respiratory chain under specific conditions. In order to obtain more suitable bacteria for the acetic acid industry, A. pasteurianus JST-S screened in this laboratory was compared with A. pasteurianus CICC 20001, a current industrial strain in China, to determine optimal fermentation parameters under different environmental stresses. The maximum total acid content of A. pasteurianus JST-S was 57.14 ± 1.09 g/L, whereas that of A. pasteurianus CICC 20001 reached 48.24 ± 1.15 g/L in a 15-L stir stank. Metabolic flux analysis was also performed to compare the reaction byproducts. Our findings revealed the potential value of the strain in improvement of industrial vinegar fermentation.

  17. Transport critical current density in flux creep model

    International Nuclear Information System (INIS)

    Wang, J.; Taylor, K.N.R.; Russell, G.J.; Yue, Y.

    1992-01-01

    The magnetic flux creep model has been used to derive the temperature dependence of the critical current density in high temperature superconductors. The generally positive curvature of the J c -T diagram is predicted in terms of two interdependent dimensionless fitting parameters. In this paper, the results are compared with both SIS and SNS junction models of these granular materials, neither of which provides a satisfactory prediction of the experimental data. A hybrid model combining the flux creep and SNS mechanisms is shown to be able to account for the linear regions of the J c -T behavior which are observed in some materials

  18. The drift flux model in the ASSERT subchannel code

    International Nuclear Information System (INIS)

    Carver, M.B.; Judd, R.A.; Kiteley, J.C.; Tahir, A.

    1987-01-01

    The ASSERT subchannel code has been developed specifically to model flow and phase distributions within CANDU fuel bundles. ASSERT uses a drift-flux model that permits the phases to have unequal velocities, and can thus model phase separation tendencies that may occur in horizontal flow. The basic principles of ASSERT are outlined, and computed results are compared against data from various experiments for validation purposes. The paper concludes with an example of the use of the code to predict critical heat flux in CANDU geometries

  19. Modeling of simultaneous ultra filtration and diafiltration with real flux

    Directory of Open Access Journals (Sweden)

    Tokoš Hela I.

    2005-01-01

    Full Text Available A mathematical model of diafiltration with variable volume is presented in this study. The characteristics of the process were examined, both with constant flux and variable flux. In the case of variable flux, the equations for the flux were taken from the literature, based on different theories. The time dependence of the macro solute concentration, the amount of out-wash liquid, the out-wash degree of the micro solute were studied. The results show that the accomplishment of a high concentration of macro solutes, required more time and out-wash liquid. In order to remove small amounts of micro solutes larger amounts of out-wash liquid must be used. For high degrees of out-washing, the velocity of the process increases and the amount of out-wash liquid decreases. It was observed that the rejection coefficient decreased with macro solute penetration through the membrane causing decrease of the process velocity.

  20. Modeling with a view to target identification in metabolic engineering: a critical evaluation of the available tools.

    Science.gov (United States)

    Maertens, Jo; Vanrolleghem, Peter A

    2010-01-01

    The state of the art tools for modeling metabolism, typically used in the domain of metabolic engineering, were reviewed. The tools considered are stoichiometric network analysis (elementary modes and extreme pathways), stoichiometric modeling (metabolic flux analysis, flux balance analysis, and carbon modeling), mechanistic and approximative modeling, cybernetic modeling, and multivariate statistics. In the context of metabolic engineering, one should be aware that the usefulness of these tools to optimize microbial metabolism for overproducing a target compound depends predominantly on the characteristic properties of that compound. Because of their shortcomings not all tools are suitable for every kind of optimization; issues like the dependence of the target compound's synthesis on severe (redox) constraints, the characteristics of its formation pathway, and the achievable/desired flux towards the target compound should play a role when choosing the optimization strategy.

  1. A theoretical model for predicting neutron fluxes for cyclic Neutron ...

    African Journals Online (AJOL)

    A theoretical model has been developed for prediction of thermal neutron fluxes required for cyclic irradiations of a sample to obtain the same activity previously used for the detection of any radionuclide of interest. The model is suitable for radiotracer production or for long-lived neutron activation products where the ...

  2. Cancer Metabolism: A Modeling Perspective

    DEFF Research Database (Denmark)

    Ghaffari, Pouyan; Mardinoglu, Adil; Nielsen, Jens

    2015-01-01

    suggest that utilization of amino acids and lipids contributes significantly to cancer cell metabolism. Also recent progresses in our understanding of carcinogenesis have revealed that cancer is a complex disease and cannot be understood through simple investigation of genetic mutations of cancerous cells...

  3. Integrating cellular metabolism into a multiscale whole-body model.

    Directory of Open Access Journals (Sweden)

    Markus Krauss

    Full Text Available Cellular metabolism continuously processes an enormous range of external compounds into endogenous metabolites and is as such a key element in human physiology. The multifaceted physiological role of the metabolic network fulfilling the catalytic conversions can only be fully understood from a whole-body perspective where the causal interplay of the metabolic states of individual cells, the surrounding tissue and the whole organism are simultaneously considered. We here present an approach relying on dynamic flux balance analysis that allows the integration of metabolic networks at the cellular scale into standardized physiologically-based pharmacokinetic models at the whole-body level. To evaluate our approach we integrated a genome-scale network reconstruction of a human hepatocyte into the liver tissue of a physiologically-based pharmacokinetic model of a human adult. The resulting multiscale model was used to investigate hyperuricemia therapy, ammonia detoxification and paracetamol-induced toxication at a systems level. The specific models simultaneously integrate multiple layers of biological organization and offer mechanistic insights into pathology and medication. The approach presented may in future support a mechanistic understanding in diagnostics and drug development.

  4. Integrating Cellular Metabolism into a Multiscale Whole-Body Model

    Science.gov (United States)

    Krauss, Markus; Schaller, Stephan; Borchers, Steffen; Findeisen, Rolf; Lippert, Jörg; Kuepfer, Lars

    2012-01-01

    Cellular metabolism continuously processes an enormous range of external compounds into endogenous metabolites and is as such a key element in human physiology. The multifaceted physiological role of the metabolic network fulfilling the catalytic conversions can only be fully understood from a whole-body perspective where the causal interplay of the metabolic states of individual cells, the surrounding tissue and the whole organism are simultaneously considered. We here present an approach relying on dynamic flux balance analysis that allows the integration of metabolic networks at the cellular scale into standardized physiologically-based pharmacokinetic models at the whole-body level. To evaluate our approach we integrated a genome-scale network reconstruction of a human hepatocyte into the liver tissue of a physiologically-based pharmacokinetic model of a human adult. The resulting multiscale model was used to investigate hyperuricemia therapy, ammonia detoxification and paracetamol-induced toxication at a systems level. The specific models simultaneously integrate multiple layers of biological organization and offer mechanistic insights into pathology and medication. The approach presented may in future support a mechanistic understanding in diagnostics and drug development. PMID:23133351

  5. Effects of drugs in subtoxic concentrations on the metabolic fluxes in human hepatoma cell line Hep G2

    International Nuclear Information System (INIS)

    Niklas, Jens; Noor, Fozia; Heinzle, Elmar

    2009-01-01

    Commonly used cytotoxicity assays assess the toxicity of a compound by measuring certain parameters which directly or indirectly correlate to the viability of the cells. However, the effects of a given compound at concentrations considerably below EC 50 values are usually not evaluated. These subtoxic effects are difficult to identify but may eventually cause severe and costly long term problems such as idiosyncratic hepatotoxicity. We determined the toxicity of three hepatotoxic compounds, namely amiodarone, diclofenac and tacrine on the human hepatoma cell line Hep G2 using an online kinetic respiration assay and analysed the effects of subtoxic concentrations of these drugs on the cellular metabolism by using metabolic flux analysis. Several changes in the metabolism could be detected upon exposure to subtoxic concentrations of the test compounds. Upon exposure to diclofenac and tacrine an increase in the TCA-cycle activity was observed which could be a signature of an uncoupling of the oxidative phosphorylation. The results indicate that metabolic flux analysis could serve as an invaluable novel tool for the investigation of the effects of drugs. The described methodology enables tracking the toxicity of compounds dynamically using the respiration assay in a range of concentrations and the metabolic flux analysis permits interesting insights into the changes in the central metabolism of the cell upon exposure to drugs.

  6. Ensemble Kinetic Modeling of Metabolic Networks from Dynamic Metabolic Profiles

    Directory of Open Access Journals (Sweden)

    Gengjie Jia

    2012-11-01

    Full Text Available Kinetic modeling of metabolic pathways has important applications in metabolic engineering, but significant challenges still remain. The difficulties faced vary from finding best-fit parameters in a highly multidimensional search space to incomplete parameter identifiability. To meet some of these challenges, an ensemble modeling method is developed for characterizing a subset of kinetic parameters that give statistically equivalent goodness-of-fit to time series concentration data. The method is based on the incremental identification approach, where the parameter estimation is done in a step-wise manner. Numerical efficacy is achieved by reducing the dimensionality of parameter space and using efficient random parameter exploration algorithms. The shift toward using model ensembles, instead of the traditional “best-fit” models, is necessary to directly account for model uncertainty during the application of such models. The performance of the ensemble modeling approach has been demonstrated in the modeling of a generic branched pathway and the trehalose pathway in Saccharomyces cerevisiae using generalized mass action (GMA kinetics.

  7. Interaction of storage carbohydrates and other cyclic fluxes with central metabolism : A quantitative approach by non-stationary 13C metabolic flux analysis

    NARCIS (Netherlands)

    Suarez-Mendez, C. A.; Hanemaaijer, M.; ten Pierick, Angela; Wolters, J. C.; Heijnen, J.J.; Wahl, S. A.

    2016-01-01

    13C labeling experiments in aerobic glucose limited cultures of Saccharomyces cerevisiae at four different growth rates (0.054; 0.101, 0.207, 0.307 h-1) are used for calculating fluxes that include intracellular cycles (e.g., storage carbohydrate cycles, exchange fluxes with amino acids), which are

  8. A dynamic metabolic flux analysis of ABE (acetone-butanol-ethanol) fermentation by Clostridium acetobutylicum ATCC 824, with riboflavin as a by-product.

    Science.gov (United States)

    Zhao, Xinhe; Kasbi, Mayssa; Chen, Jingkui; Peres, Sabine; Jolicoeur, Mario

    2017-12-01

    The present study reveals that supplementing sodium acetate (NaAc) strongly stimulates riboflavin production in acetone-butanol-ethanol (ABE) fermentation by Clostridium acetobutylicum ATCC 824 with xylose as carbon source. Riboflavin production increased from undetectable concentrations to ∼0.2 g L -1 (0.53 mM) when supplementing 60 mM NaAc. Of interest, solvents production and biomass yield were also promoted with fivefold acetone, 2.6-fold butanol, and 2.4-fold biomass adding NaAc. A kinetic metabolic model, developed to simulate ABE biosystem, with riboflavin production, revealed from a dynamic metabolic flux analysis (dMFA) simultaneous increase of riboflavin (ribA) and GTP (precursor of riboflavin) (PurM) synthesis flux rates under NaAc supplementation. The model includes 23 fluxes, 24 metabolites, and 72 kinetic parameters. It also suggested that NaAc condition has first stimulated the accumulation of intracellular metabolite intermediates during the acidogenic phase, which have then fed the solventogenic phase leading to increased ABE production. In addition, NaAc resulted in higher intracellular levels of NADH during the whole culture. Moreover, lower GTP-to-adenosine phosphates (ATP, ADP, AMP) ratio under NaAc supplemented condition suggests that GTP may have a minor role in the cell energetic metabolism compared to its contribution to riboflavin synthesis. © 2017 Wiley Periodicals, Inc.

  9. Methane Fluxes in West Siberia: 3-D Regional Model Simulation

    International Nuclear Information System (INIS)

    Jagovkina, S. V.; Karol, I. L.; Zubov, V. A.; Lagun, V. E.; Reshetnikov, A. I.; Rozanov, E. V.

    2001-01-01

    The West Siberian region is one of the main contributors of the atmospheric greenhouse gas methane due to the large areas of wetlands, rivers, lakes and numerous gas deposits situated there.But there are no reliable estimations of integral methane flux from this area into the atmosphere. For assessment of methane fluxes in West Siberia the specially constructed 3-D regional chemical transport model was applied. The 3-D distribution of methane is calculated on the basis of the current meteorological data fields(wind, temperature, geopotential) updated 4 times a day. The methane concentrations measured near the main gas fields of West Siberia in the summer season of 1999, were used for correction of methane flux intensity estimates obtained previously by comparison of measurements carried out in summer 1993 and 1996 with modelled methane mixing ratio distribution. This set of field and model experiments confirmed the preliminary conclusion about low leakage intensity: anthropogenic methane flux does not exceed 5-15% of total summer methane flux, estimated as 11-12 Mt CH 4 in summer from this region, in spite of the large areas of gas deposits located there

  10. Beaver-mediated lateral hydrologic connectivity, fluvial carbon and nutrient flux, and aquatic ecosystem metabolism

    Science.gov (United States)

    Wegener, Pam; Covino, Tim; Wohl, Ellen

    2017-06-01

    River networks that drain mountain landscapes alternate between narrow and wide valley segments. Within the wide segments, beaver activity can facilitate the development and maintenance of complex, multithread planform. Because the narrow segments have limited ability to retain water, carbon, and nutrients, the wide, multithread segments are likely important locations of retention. We evaluated hydrologic dynamics, nutrient flux, and aquatic ecosystem metabolism along two adjacent segments of a river network in the Rocky Mountains, Colorado: (1) a wide, multithread segment with beaver activity; and, (2) an adjacent (directly upstream) narrow, single-thread segment without beaver activity. We used a mass balance approach to determine the water, carbon, and nutrient source-sink behavior of each river segment across a range of flows. While the single-thread segment was consistently a source of water, carbon, and nitrogen, the beaver impacted multithread segment exhibited variable source-sink dynamics as a function of flow. Specifically, the multithread segment was a sink for water, carbon, and nutrients during high flows, and subsequently became a source as flows decreased. Shifts in river-floodplain hydrologic connectivity across flows related to higher and more variable aquatic ecosystem metabolism rates along the multithread relative to the single-thread segment. Our data suggest that beaver activity in wide valleys can create a physically complex hydrologic environment that can enhance hydrologic and biogeochemical buffering, and promote high rates of aquatic ecosystem metabolism. Given the widespread removal of beaver, determining the cumulative effects of these changes is a critical next step in restoring function in altered river networks.

  11. Metabolic flux rearrangement in the amino acid metabolism reduces ammonia stress in the α1-antitrypsin producing human AGE1.HN cell line.

    Science.gov (United States)

    Priesnitz, Christian; Niklas, Jens; Rose, Thomas; Sandig, Volker; Heinzle, Elmar

    2012-03-01

    This study focused on metabolic changes in the neuronal human cell line AGE1.HN upon increased ammonia stress. Batch cultivations of α(1)-antitrypsin (A1AT) producing AGE1.HN cells were carried out in media with initial ammonia concentrations ranging from 0mM to 5mM. Growth, A1AT production, metabolite dynamics and finally metabolic fluxes calculated by metabolite balancing were compared. Growth and A1AT production decreased with increasing ammonia concentration. The maximum A1AT concentration decreased from 0.63g/l to 0.51g/l. Central energy metabolism remained relatively unaffected exhibiting only slightly increased glycolytic flux at high initial ammonia concentration in the medium. However, the amino acid metabolism was significantly changed. Fluxes through transaminases involved in amino acid degradation were reduced concurrently with a reduced uptake of amino acids. On the other hand fluxes through transaminases working in the direction of amino acid synthesis, i.e., alanine and phosphoserine, were increased leading to increased storage of excess nitrogen in extracellular alanine and serine. Glutamate dehydrogenase flux was reversed increasingly fixing free ammonia with increasing ammonia concentration. Urea production additionally observed was associated with arginine uptake by the cells and did not increase at high ammonia stress. It was therefore not used as nitrogen sink to remove excess ammonia. The results indicate that the AGE1.HN cell line can adapt to ammonia concentrations usually present during the cultivation process to a large extent by changing metabolism but with slightly reduced A1AT production and growth. Copyright © 2012 Elsevier Inc. All rights reserved.

  12. TIGER: Toolbox for integrating genome-scale metabolic models, expression data, and transcriptional regulatory networks

    Directory of Open Access Journals (Sweden)

    Jensen Paul A

    2011-09-01

    Full Text Available Abstract Background Several methods have been developed for analyzing genome-scale models of metabolism and transcriptional regulation. Many of these methods, such as Flux Balance Analysis, use constrained optimization to predict relationships between metabolic flux and the genes that encode and regulate enzyme activity. Recently, mixed integer programming has been used to encode these gene-protein-reaction (GPR relationships into a single optimization problem, but these techniques are often of limited generality and lack a tool for automating the conversion of rules to a coupled regulatory/metabolic model. Results We present TIGER, a Toolbox for Integrating Genome-scale Metabolism, Expression, and Regulation. TIGER converts a series of generalized, Boolean or multilevel rules into a set of mixed integer inequalities. The package also includes implementations of existing algorithms to integrate high-throughput expression data with genome-scale models of metabolism and transcriptional regulation. We demonstrate how TIGER automates the coupling of a genome-scale metabolic model with GPR logic and models of transcriptional regulation, thereby serving as a platform for algorithm development and large-scale metabolic analysis. Additionally, we demonstrate how TIGER's algorithms can be used to identify inconsistencies and improve existing models of transcriptional regulation with examples from the reconstructed transcriptional regulatory network of Saccharomyces cerevisiae. Conclusion The TIGER package provides a consistent platform for algorithm development and extending existing genome-scale metabolic models with regulatory networks and high-throughput data.

  13. Comparison of Meteoroid Flux Models for Near Earth Space

    Science.gov (United States)

    Drolshagen, G.; Liou, J.-C.; Dikarev, V.; Landgraf, M.; Krag, H.; Kuiper, W.

    2007-01-01

    Over the last decade several new models for the sporadic interplanetary meteoroid flux have been developed. These include the Meteoroid Engineering Model (MEM), the Divine-Staubach model and the Interplanetary Meteoroid Engineering Model (IMEM). They typically cover mass ranges from 10-12 g (or lower) to 1 g and are applicable for model specific sun distance ranges between 0.2 A.U. and 10 A.U. Near 1 A.U. averaged fluxes (over direction and velocities) for all these models are tuned to the well established interplanetary model by Gr?n et. al. However, in many respects these models differ considerably. Examples are the velocity and directional distributions and the assumed meteoroid sources. In this paper flux predictions by the various models to Earth orbiting spacecraft are compared. Main differences are presented and analysed. The persisting differences even for near Earth space can be seen as surprising in view of the numerous ground based (optical, radar) and in-situ (captured IDPs, in-situ detectors and analysis of retrieved hardware) measurements and simulations. Remaining uncertainties and potential additional studies to overcome the existing model discrepancies are discussed.

  14. Modeling energy fluxes in heterogeneous landscapes employing a mosaic approach

    Science.gov (United States)

    Klein, Christian; Thieme, Christoph; Priesack, Eckart

    2015-04-01

    Recent studies show that uncertainties in regional and global climate and weather simulations are partly due to inadequate descriptions of the energy flux exchanges between the land surface and the atmosphere. One major shortcoming is the limitation of the grid-cell resolution, which is recommended to be about at least 3x3 km² in most models due to limitations in the model physics. To represent each individual grid cell most models select one dominant soil type and one dominant land use type. This resolution, however, is often too coarse in regions where the spatial diversity of soil and land use types are high, e.g. in Central Europe. An elegant method to avoid the shortcoming of grid cell resolution is the so called mosaic approach. This approach is part of the recently developed ecosystem model framework Expert-N 5.0. The aim of this study was to analyze the impact of the characteristics of two managed fields, planted with winter wheat and potato, on the near surface soil moistures and on the near surface energy flux exchanges of the soil-plant-atmosphere interface. The simulated energy fluxes were compared with eddy flux tower measurements between the respective fields at the research farm Scheyern, North-West of Munich, Germany. To perform these simulations, we coupled the ecosystem model Expert-N 5.0 to an analytical footprint model. The coupled model system has the ability to calculate the mixing ratio of the surface energy fluxes at a given point within one grid cell (in this case at the flux tower between the two fields). This approach accounts for the differences of the two soil types, of land use managements, and of canopy properties due to footprint size dynamics. Our preliminary simulation results show that a mosaic approach can improve modeling and analyzing energy fluxes when the land surface is heterogeneous. In this case our applied method is a promising approach to extend weather and climate models on the regional and on the global scale.

  15. Flux limitation in ultrafiltration: Osmotic pressure model and gel layer model

    NARCIS (Netherlands)

    Wijmans, J.G.; Nakao, S.; Smolders, C.A.

    1984-01-01

    The characteristic permeate flux behaviour in ultrafiltration, i.e., the existence of a limiting flux which is independent of applied pressure and membrane resistance and a linear plot of the limiting flux versus the logarithm of the feed concentration, is explained by the osmotic pressure model. In

  16. Metabolic pathway analysis of Scheffersomyces (Pichia) stipitis: effect of oxygen availability on ethanol synthesis and flux distributions.

    Science.gov (United States)

    Unrean, Pornkamol; Nguyen, Nhung H A

    2012-06-01

    Elementary mode analysis (EMA) identifies all possible metabolic states of the cell metabolic network. Investigation of these states can provide a detailed insight into the underlying metabolism in the cell. In this study, the flux states of Scheffersomyces (Pichia) stipitis metabolism were examined. It was shown that increasing oxygen levels led to a decrease of ethanol synthesis. This trend was confirmed by experimental evaluation of S. stipitis in glucose-xylose fermentation. The oxygen transfer rate for an optimal ethanol production was 1.8 mmol/l/h, which gave the ethanol yield of 0.40 g/g and the ethanol productivity of 0.25 g/l/h. For a better understanding of the cell's regulatory mechanism in response to oxygenation levels, EMA was used to examine metabolic flux patterns under different oxygen levels. Up- and downregulation of enzymes in the network during the change of culturing condition from oxygen limitation to oxygen sufficiency were identified. The results indicated the flexibility of S. stipitis metabolism to cope with oxygen availability. In addition, relevant genetic targets towards improved ethanol-producing strains under all oxygenation levels were identified. These targeted genes limited the metabolic functionality of the cell to function according to the most efficient ethanol synthesis pathways. The presented approach is promising and can contribute to the development of culture optimization and strain engineers for improved lignocellulosic ethanol production by S. stipitis.

  17. Component and system simulation models for High Flux Isotope Reactor

    International Nuclear Information System (INIS)

    Sozer, A.

    1989-08-01

    Component models for the High Flux Isotope Reactor (HFIR) have been developed. The models are HFIR core, heat exchangers, pressurizer pumps, circulation pumps, letdown valves, primary head tank, generic transport delay (pipes), system pressure, loop pressure-flow balance, and decay heat. The models were written in FORTRAN and can be run on different computers, including IBM PCs, as they do not use any specific simulation languages such as ACSL or CSMP. 14 refs., 13 figs

  18. Unique attributes of cyanobacterial metabolism revealed by improved genome-scale metabolic modeling and essential gene analysis

    Science.gov (United States)

    Broddrick, Jared T.; Rubin, Benjamin E.; Welkie, David G.; Du, Niu; Mih, Nathan; Diamond, Spencer; Lee, Jenny J.; Golden, Susan S.; Palsson, Bernhard O.

    2016-01-01

    The model cyanobacterium, Synechococcus elongatus PCC 7942, is a genetically tractable obligate phototroph that is being developed for the bioproduction of high-value chemicals. Genome-scale models (GEMs) have been successfully used to assess and engineer cellular metabolism; however, GEMs of phototrophic metabolism have been limited by the lack of experimental datasets for model validation and the challenges of incorporating photon uptake. Here, we develop a GEM of metabolism in S. elongatus using random barcode transposon site sequencing (RB-TnSeq) essential gene and physiological data specific to photoautotrophic metabolism. The model explicitly describes photon absorption and accounts for shading, resulting in the characteristic linear growth curve of photoautotrophs. GEM predictions of gene essentiality were compared with data obtained from recent dense-transposon mutagenesis experiments. This dataset allowed major improvements to the accuracy of the model. Furthermore, discrepancies between GEM predictions and the in vivo dataset revealed biological characteristics, such as the importance of a truncated, linear TCA pathway, low flux toward amino acid synthesis from photorespiration, and knowledge gaps within nucleotide metabolism. Coupling of strong experimental support and photoautotrophic modeling methods thus resulted in a highly accurate model of S. elongatus metabolism that highlights previously unknown areas of S. elongatus biology. PMID:27911809

  19. Interaction of storage carbohydrates and other cyclic fluxes with central metabolism: A quantitative approach by non-stationary 13C metabolic flux analysis.

    Science.gov (United States)

    Suarez-Mendez, C A; Hanemaaijer, M; Ten Pierick, Angela; Wolters, J C; Heijnen, J J; Wahl, S A

    2016-12-01

    13 C labeling experiments in aerobic glucose limited cultures of Saccharomyces cerevisiae at four different growth rates (0.054; 0.101, 0.207, 0.307 h -1 ) are used for calculating fluxes that include intracellular cycles (e.g., storage carbohydrate cycles, exchange fluxes with amino acids), which are rearranged depending on the growth rate. At low growth rates the impact of the storage carbohydrate recycle is relatively more significant than at high growth rates due to a higher concentration of these materials in the cell (up to 560-fold) and higher fluxes relative to the glucose uptake rate (up to 16%). Experimental observations suggest that glucose can be exported to the extracellular space, and that its source is related to storage carbohydrates, most likely via the export and subsequent extracellular breakdown of trehalose. This hypothesis is strongly supported by 13 C-labeling experimental data, measured extracellular trehalose, and the corresponding flux estimations.

  20. Regularized Biot–Savart Laws for Modeling Magnetic Flux Ropes

    Science.gov (United States)

    Titov, Viacheslav S.; Downs, Cooper; Mikić, Zoran; Török, Tibor; Linker, Jon A.; Caplan, Ronald M.

    2018-01-01

    Many existing models assume that magnetic flux ropes play a key role in solar flares and coronal mass ejections (CMEs). It is therefore important to develop efficient methods for constructing flux-rope configurations constrained by observed magnetic data and the morphology of the pre-eruptive source region. For this purpose, we have derived and implemented a compact analytical form that represents the magnetic field of a thin flux rope with an axis of arbitrary shape and circular cross-sections. This form implies that the flux rope carries axial current I and axial flux F, so that the respective magnetic field is the curl of the sum of axial and azimuthal vector potentials proportional to I and F, respectively. We expressed the vector potentials in terms of modified Biot–Savart laws, whose kernels are regularized at the axis in such a way that, when the axis is straight, these laws define a cylindrical force-free flux rope with a parabolic profile for the axial current density. For the cases we have studied so far, we determined the shape of the rope axis by following the polarity inversion line of the eruptions’ source region, using observed magnetograms. The height variation along the axis and other flux-rope parameters are estimated by means of potential-field extrapolations. Using this heuristic approach, we were able to construct pre-eruption configurations for the 2009 February 13 and 2011 October 1 CME events. These applications demonstrate the flexibility and efficiency of our new method for energizing pre-eruptive configurations in simulations of CMEs.

  1. Quantitative Metabolomics and Instationary 13C-Metabolic Flux Analysis Reveals Impact of Recombinant Protein Production on Trehalose and Energy Metabolism in Pichia pastoris

    Directory of Open Access Journals (Sweden)

    Joel Jordà

    2014-05-01

    Full Text Available Pichia pastoris has been recognized as an effective host for recombinant protein production. In this work, we combine metabolomics and instationary 13C metabolic flux analysis (INST 13C-MFA using GC-MS and LC-MS/MS to evaluate the potential impact of the production of a Rhizopus oryzae lipase (Rol on P. pastoris central carbon metabolism. Higher oxygen uptake and CO2 production rates and slightly reduced biomass yield suggest an increased energy demand for the producing strain. This observation is further confirmed by 13C-based metabolic flux analysis. In particular, the flux through the methanol oxidation pathway and the TCA cycle was increased in the Rol-producing strain compared to the reference strain. Next to changes in the flux distribution, significant variations in intracellular metabolite concentrations were observed. Most notably, the pools of trehalose, which is related to cellular stress response, and xylose, which is linked to methanol assimilation, were significantly increased in the recombinant strain.

  2. Effects of temperature and UVR on organic matter fluxes and the metabolic activity of Acropora muricata

    Directory of Open Access Journals (Sweden)

    Lucile Courtial

    2017-08-01

    Full Text Available Coral bleaching events are predicted to occur more frequently in the coming decades with global warming. The susceptibility of corals to bleaching during thermal stress episodes depends on many factors, including the magnitude of thermal stress and irradiance. The interactions among these two factors, and in particular with ultra-violet radiation (UVR, the most harmful component of light, are more complex than assumed, and are not yet well understood. This paper explores the individual and combined effects of temperature and UVR on the metabolism of Acropora muricata, one of the most abundant coral species worldwide. Particulate and dissolved organic matter (POM/DOM fluxes and organic matter (OM degradation by the mucus-associated bacteria were also monitored in all conditions. The results show that UVR exposure exacerbated the temperature-induced bleaching, but did not affect OM fluxes, which were only altered by seawater warming. Temperature increase induced a shift from POM release and DOM uptake in healthy corals to POM uptake and DOM release in stressed ones. POM uptake was linked to a significant grazing of pico- and nanoplankton particles during the incubation, to fulfil the energetic requirements of A. muricata in the absence of autotrophy. Finally, OM degradation by mucus-associated bacterial activity was unaffected by UVR exposure, but significantly increased under high temperature. Altogether, our results demonstrate that seawater warming and UVR not only affect coral physiology, but also the way corals interact with the surrounding seawater, with potential consequences for coral reef biogeochemical cycles and food webs.

  3. Uncertainties in (E)UV model atmosphere fluxes

    Science.gov (United States)

    Rauch, T.

    2008-04-01

    Context: During the comparison of synthetic spectra calculated with two NLTE model atmosphere codes, namely TMAP and TLUSTY, we encounter systematic differences in the EUV fluxes due to the treatment of level dissolution by pressure ionization. Aims: In the case of Sirius B, we demonstrate an uncertainty in modeling the EUV flux reliably in order to challenge theoreticians to improve the theory of level dissolution. Methods: We calculated synthetic spectra for hot, compact stars using state-of-the-art NLTE model-atmosphere techniques. Results: Systematic differences may occur due to a code-specific cutoff frequency of the H I Lyman bound-free opacity. This is the case for TMAP and TLUSTY. Both codes predict the same flux level at wavelengths lower than about 1500 Å for stars with effective temperatures (T_eff) below about 30 000 K only, if the same cutoff frequency is chosen. Conclusions: The theory of level dissolution in high-density plasmas, which is available for hydrogen only should be generalized to all species. Especially, the cutoff frequencies for the bound-free opacities should be defined in order to make predictions of UV fluxes more reliable.

  4. Computational Modeling of Lipid Metabolism in Yeast

    Directory of Open Access Journals (Sweden)

    Vera Schützhold

    2016-09-01

    Full Text Available Lipid metabolism is essential for all major cell functions and has recently gained increasing attention in research and health studies. However, mathematical modeling by means of classical approaches such as stoichiometric networks and ordinary differential equation systems has not yet provided satisfactory insights, due to the complexity of lipid metabolism characterized by many different species with only slight differences and by promiscuous multifunctional enzymes.Here, we present a object-oriented stochastic model approach as a way to cope with the complex lipid metabolic network. While all lipid species are treated objects in the model, they can be modified by the respective converting reactions based on reaction rules, a hybrid method that integrates benefits of agent-based and classical stochastic simulation. This approach allows to follow the dynamics of all lipid species with different fatty acids, different degrees of saturation and different headgroups over time and to analyze the effect of parameter changes, potential mutations in the catalyzing enzymes or provision of different precursors. Applied to yeast metabolism during one cell cycle period, we could analyze the distribution of all lipids to the various membranes in time-dependent manner.The presented approach allows to efficiently treat the complexity of cellular lipid metabolism and to derive conclusions on the time- and location-dependent distributions of lipid species and their properties such as saturation. It is widely applicable, easily extendable and will provide further insights in healthy and diseased states of cell metabolism.

  5. Flux balance modeling to predict bacterial survival during pulsed-activity events

    Science.gov (United States)

    Jose, Nicholas A.; Lau, Rebecca; Swenson, Tami L.; Klitgord, Niels; Garcia-Pichel, Ferran; Bowen, Benjamin P.; Baran, Richard; Northen, Trent R.

    2018-04-01

    Desert biological soil crusts (BSCs) are cyanobacteria-dominated surface soil microbial communities common to plant interspaces in arid environments. The capability to significantly dampen their metabolism allows them to exist for extended periods in a desiccated dormant state that is highly robust to environmental stresses. However, within minutes of wetting, metabolic functions reboot, maximizing activity during infrequent permissive periods. Microcoleus vaginatus, a primary producer within the crust ecosystem and an early colonizer, initiates crust formation by binding particles in the upper layer of soil via exopolysaccharides, making microbial dominated biological soil crusts highly dependent on the viability of this organism. Previous studies have suggested that biopolymers play a central role in the survival of this organism by powering resuscitation, rapidly forming compatible solutes, and fueling metabolic activity in dark, hydrated conditions. To elucidate the mechanism of this phenomenon and provide a basis for future modeling of BSCs, we developed a manually curated, genome-scale metabolic model of Microcoleus vaginatus (iNJ1153). To validate this model, gas chromatography-mass spectroscopy (GC-MS) and liquid chromatography-mass spectroscopy (LC-MS) were used to characterize the rate of biopolymer accumulation and depletion in in hydrated Microcoleus vaginatus under light and dark conditions. Constraint-based flux balance analysis showed agreement between model predictions and experimental reaction fluxes. A significant amount of consumed carbon and light energy is invested into storage molecules glycogen and polyphosphate, while β-polyhydroxybutyrate may function as a secondary resource. Pseudo-steady-state modeling suggests that glycogen, the primary carbon source with the fastest depletion rate, will be exhausted if M. vaginatus experiences dark wetting events 4 times longer than light wetting events.

  6. Rodent Models for Metabolic Syndrome Research

    Directory of Open Access Journals (Sweden)

    Sunil K. Panchal

    2011-01-01

    Full Text Available Rodents are widely used to mimic human diseases to improve understanding of the causes and progression of disease symptoms and to test potential therapeutic interventions. Chronic diseases such as obesity, diabetes and hypertension, together known as the metabolic syndrome, are causing increasing morbidity and mortality. To control these diseases, research in rodent models that closely mimic the changes in humans is essential. This review will examine the adequacy of the many rodent models of metabolic syndrome to mimic the causes and progression of the disease in humans. The primary criterion will be whether a rodent model initiates all of the signs, especially obesity, diabetes, hypertension and dysfunction of the heart, blood vessels, liver and kidney, primarily by diet since these are the diet-induced signs in humans with metabolic syndrome. We conclude that the model that comes closest to fulfilling this criterion is the high carbohydrate, high fat-fed male rodent.

  7. Analog model for analysis of spatial instability of neutron flux

    International Nuclear Information System (INIS)

    Radanovic, Lj.

    1964-12-01

    The objective of this task was to develop a model for analysing spatial instability of the neutron flux and defining the optimum number and position of regulating rods. The developed model enables calculation of higher harmonics to be taken into account for each type of reactor, to define zones for regulation rods, position and number of points for detecting reactor state, and number and position of the regulating rods

  8. Interaction of storage carbohydrates and other cyclic fluxes with central metabolism: A quantitative approach by non-stationary 13C metabolic flux analysis

    Directory of Open Access Journals (Sweden)

    C.A. Suarez-Mendez

    2016-12-01

    Full Text Available 13C labeling experiments in aerobic glucose limited cultures of Saccharomyces cerevisiae at four different growth rates (0.054; 0.101, 0.207, 0.307 h−1 are used for calculating fluxes that include intracellular cycles (e.g., storage carbohydrate cycles, exchange fluxes with amino acids, which are rearranged depending on the growth rate. At low growth rates the impact of the storage carbohydrate recycle is relatively more significant than at high growth rates due to a higher concentration of these materials in the cell (up to 560-fold and higher fluxes relative to the glucose uptake rate (up to 16%. Experimental observations suggest that glucose can be exported to the extracellular space, and that its source is related to storage carbohydrates, most likely via the export and subsequent extracellular breakdown of trehalose. This hypothesis is strongly supported by 13C-labeling experimental data, measured extracellular trehalose, and the corresponding flux estimations. Keywords: Non-stationary 13C labeling, Flux estimation, Trehalose, Glycogen, Amino acids

  9. Development of a screening approach for exploring cell factory potential through metabolic flux analysis and physiology

    DEFF Research Database (Denmark)

    Knudsen, Peter Boldsen; Nielsen, Kristian Fog; Thykær, Jette

    2012-01-01

    The recent developments within the field of metabolic engineering have significantly increased the speed by which fungal recombinant strains are being constructed, pushing focus towards physiological characterisation and analysis. This raises demand for a tool for diligent analysis of the recombi......The recent developments within the field of metabolic engineering have significantly increased the speed by which fungal recombinant strains are being constructed, pushing focus towards physiological characterisation and analysis. This raises demand for a tool for diligent analysis...... of the validation, already well described fungal strains were selected and tested using the described method and the developed method was subsequently used to test recombinant fungal strains producing the model polyketide 6-methylsalicylic acid. Diligent application of this strategy significantly reduces the cost...

  10. 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

  11. Linking genes to ecosystem trace gas fluxes in a large-scale model system

    Science.gov (United States)

    Meredith, L. K.; Cueva, A.; Volkmann, T. H. M.; Sengupta, A.; Troch, P. A.

    2017-12-01

    Soil microorganisms mediate biogeochemical cycles through biosphere-atmosphere gas exchange with significant impact on atmospheric trace gas composition. Improving process-based understanding of these microbial populations and linking their genomic potential to the ecosystem-scale is a challenge, particularly in soil systems, which are heterogeneous in biodiversity, chemistry, and structure. In oligotrophic systems, such as the Landscape Evolution Observatory (LEO) at Biosphere 2, atmospheric trace gas scavenging may supply critical metabolic needs to microbial communities, thereby promoting tight linkages between microbial genomics and trace gas utilization. This large-scale model system of three initially homogenous and highly instrumented hillslopes facilitates high temporal resolution characterization of subsurface trace gas fluxes at hundreds of sampling points, making LEO an ideal location to study microbe-mediated trace gas fluxes from the gene to ecosystem scales. Specifically, we focus on the metabolism of ubiquitous atmospheric reduced trace gases hydrogen (H2), carbon monoxide (CO), and methane (CH4), which may have wide-reaching impacts on microbial community establishment, survival, and function. Additionally, microbial activity on LEO may facilitate weathering of the basalt matrix, which can be studied with trace gas measurements of carbonyl sulfide (COS/OCS) and carbon dioxide (O-isotopes in CO2), and presents an additional opportunity for gene to ecosystem study. This work will present initial measurements of this suite of trace gases to characterize soil microbial metabolic activity, as well as links between spatial and temporal variability of microbe-mediated trace gas fluxes in LEO and their relation to genomic-based characterization of microbial community structure (phylogenetic amplicons) and genetic potential (metagenomics). Results from the LEO model system will help build understanding of the importance of atmospheric inputs to

  12. Regularized Biot-Savart Laws for Modeling Magnetic Flux Ropes

    Science.gov (United States)

    Titov, Viacheslav; Downs, Cooper; Mikic, Zoran; Torok, Tibor; Linker, Jon A.

    2017-08-01

    Many existing models assume that magnetic flux ropes play a key role in solar flares and coronal mass ejections (CMEs). It is therefore important to develop efficient methods for constructing flux-rope configurations constrained by observed magnetic data and the initial morphology of CMEs. As our new step in this direction, we have derived and implemented a compact analytical form that represents the magnetic field of a thin flux rope with an axis of arbitrary shape and a circular cross-section. This form implies that the flux rope carries axial current I and axial flux F, so that the respective magnetic field is a curl of the sum of toroidal and poloidal vector potentials proportional to I and F, respectively. The vector potentials are expressed in terms of Biot-Savart laws whose kernels are regularized at the rope axis. We regularized them in such a way that for a straight-line axis the form provides a cylindrical force-free flux rope with a parabolic profile of the axial current density. So far, we set the shape of the rope axis by tracking the polarity inversion lines of observed magnetograms and estimating its height and other parameters of the rope from a calculated potential field above these lines. In spite of this heuristic approach, we were able to successfully construct pre-eruption configurations for the 2009 February13 and 2011 October 1 CME events. These applications demonstrate that our regularized Biot-Savart laws are indeed a very flexible and efficient method for energizing initial configurations in MHD simulations of CMEs. We discuss possible ways of optimizing the axis paths and other extensions of the method in order to make it more useful and robust.Research supported by NSF, NASA's HSR and LWS Programs, and AFOSR.

  13. MID Max: LC–MS/MS Method for Measuring the Precursor and Product Mass Isotopomer Distributions of Metabolic Intermediates and Cofactors for Metabolic Flux Analysis Applications

    DEFF Research Database (Denmark)

    McCloskey, Douglas; Young, Jamey D.; Xu, Sibei

    2016-01-01

    The analytical challenges to acquire accurate isotopic data of intracellular metabolic intermediates for stationary, nonstationary, and dynamic metabolic flux analysis (MFA) are numerous. This work presents MID Max, a novel LC–MS/MS workflow, acquisition, and isotopomer deconvolution method for MFA...... that takes advantage of additional scan types that maximizes the number of mass isotopomer distributions (MIDs) that can be acquired in a given experiment. The analytical method was found to measure the MIDs of 97 metabolites, corresponding to 74 unique metabolite-fragment pairs (32 precursor spectra and 42...

  14. Modelling of cadmium fluxes on energy crop land

    International Nuclear Information System (INIS)

    Palm, V.

    1992-04-01

    The flux of cadmium on energy crop land is investigated. Three mechanisms are accounted for; Uptake by plant, transport with water, and sorption to soil. Sorption is described with Freundlich isotherms. The system is simulated mathematically in order to estimate the sensitivity and importance of different parameters on the cadmium flow and sorption. The water flux through the soil and the uptake by plants are simulated with a hydrological model, SOIL. The simulated time period is two years. The parameters describing root distribution and evaporation due to crop are taken from measurements on energy crop (Salix). The resulting water flux, water content in the soil profile and the water uptake into roots, for each day and soil compartment, are used in the cadmium sorption simulation. In the cadmium sorption simulation the flux and equilibrium chemistry of cadmium is calculated. It is shown that the amount of cadmium that accumulates in the plant, and the depth to which the applied cadmium reaches depends strongly on the constants in the sorption isotherm. With an application of 10 mg Cd/m 2 in the given range of Freundlich equations, the simulations gave a plant uptake of between 0 and 30 % of the applied cadmium in two years. At higher concentrations, where cadmium sorption can be described by nonlinear isotherms, more cadmium is present in soil water and is generally more bioavailable. 25 refs

  15. Metabolic Flux Distribution during Defatting of Steatotic Human Hepatoma (HepG2 Cells

    Directory of Open Access Journals (Sweden)

    Gabriel Yarmush

    2016-01-01

    Full Text Available Methods that rapidly decrease fat in steatotic hepatocytes may be helpful to recover severely fatty livers for transplantation. Defatting kinetics are highly dependent upon the extracellular medium composition; however, the pathways involved are poorly understood. Steatosis was induced in human hepatoma cells (HepG2 by exposure to high levels of free fatty acids, followed by defatting using plain medium containing no fatty acids, or medium supplemented with a cocktail of defatting agents previously described before. We measured the levels of 28 extracellular metabolites and intracellular triglyceride, and fed the data into a steady-state mass balance model to estimate strictly intracellular fluxes. We found that during defatting, triglyceride content decreased, while beta-oxidation, the tricarboxylic acid cycle, and the urea cycle increased. These fluxes were augmented by defatting agents, and even more so by hyperoxic conditions. In all defatting conditions, the rate of extracellular glucose uptake/release was very small compared to the internal supply from glycogenolysis, and glycolysis remained highly active. Thus, in steatotic HepG2 cells, glycolysis and fatty acid oxidation may co-exist. Together, these pathways generate reducing equivalents that are supplied to mitochondrial oxidative phosphorylation.

  16. Context-Specific Metabolic Model Extraction Based on Regularized Least Squares Optimization.

    Directory of Open Access Journals (Sweden)

    Semidán Robaina Estévez

    Full Text Available Genome-scale metabolic models have proven highly valuable in investigating cell physiology. Recent advances include the development of methods to extract context-specific models capable of describing metabolism under more specific scenarios (e.g., cell types. Yet, none of the existing computational approaches allows for a fully automated model extraction and determination of a flux distribution independent of user-defined parameters. Here we present RegrEx, a fully automated approach that relies solely on context-specific data and ℓ1-norm regularization to extract a context-specific model and to provide a flux distribution that maximizes its correlation to data. Moreover, the publically available implementation of RegrEx was used to extract 11 context-specific human models using publicly available RNAseq expression profiles, Recon1 and also Recon2, the most recent human metabolic model. The comparison of the performance of RegrEx and its contending alternatives demonstrates that the proposed method extracts models for which both the structure, i.e., reactions included, and the flux distributions are in concordance with the employed data. These findings are supported by validation and comparison of method performance on additional data not used in context-specific model extraction. Therefore, our study sets the ground for applications of other regularization techniques in large-scale metabolic modeling.

  17. Predicting growth of the healthy infant using a genome scale metabolic model

    DEFF Research Database (Denmark)

    Nilsson, Avlant; Mardinoglu, Adil; Nielsen, Jens

    2017-01-01

    to simulate the mechanisms of growth and integrate data about breast-milk intake and composition with the infant's biomass and energy expenditure of major organs. The model predicted daily metabolic fluxes from birth to age 6 months, and accurately reproduced standard growth curves and changes in body...

  18. Predicting growth of the healthy infant using a genome scale metabolic model.

    Science.gov (United States)

    Nilsson, Avlant; Mardinoglu, Adil; Nielsen, Jens

    2017-01-01

    An estimated 165 million children globally have stunted growth, and extensive growth data are available. Genome scale metabolic models allow the simulation of molecular flux over each metabolic enzyme, and are well adapted to analyze biological systems. We used a human genome scale metabolic model to simulate the mechanisms of growth and integrate data about breast-milk intake and composition with the infant's biomass and energy expenditure of major organs. The model predicted daily metabolic fluxes from birth to age 6 months, and accurately reproduced standard growth curves and changes in body composition. The model corroborates the finding that essential amino and fatty acids do not limit growth, but that energy is the main growth limiting factor. Disruptions to the supply and demand of energy markedly affected the predicted growth, indicating that elevated energy expenditure may be detrimental. The model was used to simulate the metabolic effect of mineral deficiencies, and showed the greatest growth reduction for deficiencies in copper, iron, and magnesium ions which affect energy production through oxidative phosphorylation. The model and simulation method were integrated to a platform and shared with the research community. The growth model constitutes another step towards the complete representation of human metabolism, and may further help improve the understanding of the mechanisms underlying stunting.

  19. A recruiting protein of geranylgeranyl diphosphate synthase controls metabolic flux toward chlorophyll biosynthesis in rice.

    Science.gov (United States)

    Zhou, Fei; Wang, Cheng-Yuan; Gutensohn, Michael; Jiang, Ling; Zhang, Peng; Zhang, Dabing; Dudareva, Natalia; Lu, Shan

    2017-06-27

    In plants, geranylgeranyl diphosphate (GGPP) is produced by plastidic GGPP synthase (GGPPS) and serves as a precursor for vital metabolic branches, including chlorophyll, carotenoid, and gibberellin biosynthesis. However, molecular mechanisms regulating GGPP allocation among these biosynthetic pathways localized in the same subcellular compartment are largely unknown. We found that rice contains only one functionally active GGPPS, OsGGPPS1, in chloroplasts. A functionally active homodimeric enzyme composed of two OsGGPPS1 subunits is located in the stroma. In thylakoid membranes, however, the GGPPS activity resides in a heterodimeric enzyme composed of one OsGGPPS1 subunit and GGPPS recruiting protein (OsGRP). OsGRP is structurally most similar to members of the geranyl diphosphate synthase small subunit type II subfamily. In contrast to members of this subfamily, OsGRP enhances OsGGPPS1 catalytic efficiency and specificity of GGPP production on interaction with OsGGPPS1. Structural biology and protein interaction analyses demonstrate that affinity between OsGRP and OsGGPPS1 is stronger than between two OsGGPPS1 molecules in homodimers. OsGRP determines OsGGPPS1 suborganellar localization and directs it to a large protein complex in thylakoid membranes, consisting of geranylgeranyl reductase (OsGGR), light-harvesting-like protein 3 (OsLIL3), protochlorophyllide oxidoreductase (OsPORB), and chlorophyll synthase (OsCHLG). Taken together, genetic and biochemical analyses suggest OsGRP functions in recruiting OsGGPPS1 from the stroma toward thylakoid membranes, thus providing a mechanism to control GGPP flux toward chlorophyll biosynthesis.

  20. Ethanol-metabolizing pathways in deermice. Estimation of flux calculated from isotope effects

    International Nuclear Information System (INIS)

    Alderman, J.; Takagi, T.; Lieber, C.S.

    1987-01-01

    The apparent deuterium isotope effects on Vmax/Km (D(V/K] of ethanol oxidation in two deermouse strains (one having and one lacking hepatic alcohol dehydrogenase (ADH] were used to calculate flux through the ADH, microsomal ethanol-oxidizing system (MEOS), and catalase pathways. In vitro, D(V/K) values were 3.22 for ADH, 1.13 for MEOS, and 1.83 for catalase under physiological conditions of pH, temperature, and ionic strength. In vivo, in deermice lacking ADH (ADH-), D(V/K) was 1.20 +/- 0.09 (mean +/- S.E.) at 7.0 +/- 0.5 mM blood ethanol and 1.08 +/- 0.10 at 57.8 +/- 10.2 mM blood ethanol, consistent with ethanol oxidation principally by MEOS. Pretreatment of ADH- animals with the catalase inhibitor 3-amino-1,2,4-triazole did not significantly change D(V/K). ADH+ deermice exhibited D(V/K) values of 1.87 +/- 0.06 (untreated), 1.71 +/- 0.13 (pretreated with 3-amino-1,2,4-triazole), and 1.24 +/- 0.13 (after the ADH inhibitor, 4-methylpyrazole) at 5-7 mM blood ethanol levels. At elevated blood ethanol concentrations (58.1 +/- 2.4 mM), a D(V/K) of 1.37 +/- 0.21 was measured in the ADH+ strain. For measured D(V/K) values to accurately reflect pathway contributions, initial reaction conditions are essential. These were shown to exist by the following criteria: negligible fractional conversion of substrate to product and no measurable back reaction in deermice having a reversible enzyme (ADH). Thus, calculations from D(V/K) indicate that, even when ADH is present, non-ADH pathways (mostly MEOS) participate significantly in ethanol metabolism at all concentrations tested and play a major role at high levels

  1. Neuro-fuzzy model of homocysteine metabolism

    Indian Academy of Sciences (India)

    In view of well-documented association of hyperhomocysteinaemia with a wide spectrum of diseases and higher incidence of vitamin deficiencies in Indians, we proposed a mathematical model to forecast the role of demographic and geneticvariables in influencing homocysteine metabolism and investigated the influence ...

  2. Metabolic modelling of polyhydroxyalkanoate copolymers production by mixed microbial cultures

    Directory of Open Access Journals (Sweden)

    Reis Maria AM

    2008-07-01

    Full Text Available Abstract Background This paper presents a metabolic model describing the production of polyhydroxyalkanoate (PHA copolymers in mixed microbial cultures, using mixtures of acetic and propionic acid as carbon source material. Material and energetic balances were established on the basis of previously elucidated metabolic pathways. Equations were derived for the theoretical yields for cell growth and PHA production on mixtures of acetic and propionic acid as functions of the oxidative phosphorylation efficiency, P/O ratio. The oxidative phosphorylation efficiency was estimated from rate measurements, which in turn allowed the estimation of the theoretical yield coefficients. Results The model was validated with experimental data collected in a sequencing batch reactor (SBR operated under varying feeding conditions: feeding of acetic and propionic acid separately (control experiments, and the feeding of acetic and propionic acid simultaneously. Two different feast and famine culture enrichment strategies were studied: (i either with acetate or (ii with propionate as carbon source material. Metabolic flux analysis (MFA was performed for the different feeding conditions and culture enrichment strategies. Flux balance analysis (FBA was used to calculate optimal feeding scenarios for high quality PHA polymers production, where it was found that a suitable polymer would be obtained when acetate is fed in excess and the feeding rate of propionate is limited to ~0.17 C-mol/(C-mol.h. The results were compared with published pure culture metabolic studies. Conclusion Acetate was more conducive toward the enrichment of a microbial culture with higher PHA storage fluxes and yields as compared to propionate. The P/O ratio was not only influenced by the selected microbial culture, but also by the carbon substrate fed to each culture, where higher P/O ratio values were consistently observed for acetate than propionate. MFA studies suggest that when mixtures of

  3. Metabolic flux distribution and mathematical models for dynamic ...

    African Journals Online (AJOL)

    user

    2011-03-21

    Mar 21, 2011 ... RNA and DNA), which require NADPH as a redox- equivalent. In Escherichia ...... sleep. Afr. J. Biotechnol. 7(6): 712-713. Hofmann E, Hopperschlager G (1982). ... Effect of cra gene knockout together with edd and iclR genes.

  4. IsoDesign: a software for optimizing the design of 13C-metabolic flux analysis experiments.

    Science.gov (United States)

    Millard, Pierre; Sokol, Serguei; Letisse, Fabien; Portais, Jean-Charles

    2014-01-01

    The growing demand for (13) C-metabolic flux analysis ((13) C-MFA) in the field of metabolic engineering and systems biology is driving the need to rationalize expensive and time-consuming (13) C-labeling experiments. Experimental design is a key step in improving both the number of fluxes that can be calculated from a set of isotopic data and the precision of flux values. We present IsoDesign, a software that enables these parameters to be maximized by optimizing the isotopic composition of the label input. It can be applied to (13) C-MFA investigations using a broad panel of analytical tools (MS, MS/MS, (1) H NMR, (13) C NMR, etc.) individually or in combination. It includes a visualization module to intuitively select the optimal label input depending on the biological question to be addressed. Applications of IsoDesign are described, with an example of the entire (13) C-MFA workflow from the experimental design to the flux map including important practical considerations. IsoDesign makes the experimental design of (13) C-MFA experiments more accessible to a wider biological community. IsoDesign is distributed under an open source license at http://metasys.insa-toulouse.fr/software/isodes/ © 2013 Wiley Periodicals, Inc.

  5. Scalar flux modeling in turbulent flames using iterative deconvolution

    Science.gov (United States)

    Nikolaou, Z. M.; Cant, R. S.; Vervisch, L.

    2018-04-01

    In the context of large eddy simulations, deconvolution is an attractive alternative for modeling the unclosed terms appearing in the filtered governing equations. Such methods have been used in a number of studies for non-reacting and incompressible flows; however, their application in reacting flows is limited in comparison. Deconvolution methods originate from clearly defined operations, and in theory they can be used in order to model any unclosed term in the filtered equations including the scalar flux. In this study, an iterative deconvolution algorithm is used in order to provide a closure for the scalar flux term in a turbulent premixed flame by explicitly filtering the deconvoluted fields. The assessment of the method is conducted a priori using a three-dimensional direct numerical simulation database of a turbulent freely propagating premixed flame in a canonical configuration. In contrast to most classical a priori studies, the assessment is more stringent as it is performed on a much coarser mesh which is constructed using the filtered fields as obtained from the direct simulations. For the conditions tested in this study, deconvolution is found to provide good estimates both of the scalar flux and of its divergence.

  6. HTS axial flux induction motor with analytic and FEA modeling

    Energy Technology Data Exchange (ETDEWEB)

    Li, S., E-mail: alexlee.zn@gmail.com; Fan, Y.; Fang, J.; Qin, W.; Lv, G.; Li, J.H.

    2013-11-15

    Highlights: •A high temperature superconductor axial flux induction motor and a novel maglev scheme are presented. •Analytic method and finite element method have been adopted to model the motor and to calculate the force. •Magnetic field distribution in HTS coil is calculated by analytic method. •An effective method to improve the critical current of HTS coil is presented. •AC losses of HTS coils in the HTS axial flux induction motor are estimated and tested. -- Abstract: This paper presents a high-temperature superconductor (HTS) axial-flux induction motor, which can output levitation force and torque simultaneously. In order to analyze the character of the force, analytic method and finite element method are adopted to model the motor. To make sure the HTS can carry sufficiently large current and work well, the magnetic field distribution in HTS coil is calculated. An effective method to improve the critical current of HTS coil is presented. Then, AC losses in HTS windings in the motor are estimated and tested.

  7. Prompt atmospheric neutrino fluxes: perturbative QCD models and nuclear effects

    Energy Technology Data Exchange (ETDEWEB)

    Bhattacharya, Atri [Department of Physics, University of Arizona,1118 E. 4th St. Tucson, AZ 85704 (United States); Space sciences, Technologies and Astrophysics Research (STAR) Institute,Université de Liège,Bât. B5a, 4000 Liège (Belgium); Enberg, Rikard [Department of Physics and Astronomy, Uppsala University,Box 516, SE-75120 Uppsala (Sweden); Jeong, Yu Seon [Department of Physics and IPAP, Yonsei University,50 Yonsei-ro Seodaemun-gu, Seoul 03722 (Korea, Republic of); National Institute of Supercomputing and Networking, KISTI,245 Daehak-ro, Yuseong-gu, Daejeon 34141 (Korea, Republic of); Kim, C.S. [Department of Physics and IPAP, Yonsei University,50 Yonsei-ro Seodaemun-gu, Seoul 03722 (Korea, Republic of); Reno, Mary Hall [Department of Physics and Astronomy, University of Iowa,Iowa City, Iowa 52242 (United States); Sarcevic, Ina [Department of Physics, University of Arizona,1118 E. 4th St. Tucson, AZ 85704 (United States); Department of Astronomy, University of Arizona,933 N. Cherry Ave., Tucson, AZ 85721 (United States); Stasto, Anna [Department of Physics, 104 Davey Lab, The Pennsylvania State University,University Park, PA 16802 (United States)

    2016-11-28

    We evaluate the prompt atmospheric neutrino flux at high energies using three different frameworks for calculating the heavy quark production cross section in QCD: NLO perturbative QCD, k{sub T} factorization including low-x resummation, and the dipole model including parton saturation. We use QCD parameters, the value for the charm quark mass and the range for the factorization and renormalization scales that provide the best description of the total charm cross section measured at fixed target experiments, at RHIC and at LHC. Using these parameters we calculate differential cross sections for charm and bottom production and compare with the latest data on forward charm meson production from LHCb at 7 TeV and at 13 TeV, finding good agreement with the data. In addition, we investigate the role of nuclear shadowing by including nuclear parton distribution functions (PDF) for the target air nucleus using two different nuclear PDF schemes. Depending on the scheme used, we find the reduction of the flux due to nuclear effects varies from 10% to 50% at the highest energies. Finally, we compare our results with the IceCube limit on the prompt neutrino flux, which is already providing valuable information about some of the QCD models.

  8. HTS axial flux induction motor with analytic and FEA modeling

    International Nuclear Information System (INIS)

    Li, S.; Fan, Y.; Fang, J.; Qin, W.; Lv, G.; Li, J.H.

    2013-01-01

    Highlights: •A high temperature superconductor axial flux induction motor and a novel maglev scheme are presented. •Analytic method and finite element method have been adopted to model the motor and to calculate the force. •Magnetic field distribution in HTS coil is calculated by analytic method. •An effective method to improve the critical current of HTS coil is presented. •AC losses of HTS coils in the HTS axial flux induction motor are estimated and tested. -- Abstract: This paper presents a high-temperature superconductor (HTS) axial-flux induction motor, which can output levitation force and torque simultaneously. In order to analyze the character of the force, analytic method and finite element method are adopted to model the motor. To make sure the HTS can carry sufficiently large current and work well, the magnetic field distribution in HTS coil is calculated. An effective method to improve the critical current of HTS coil is presented. Then, AC losses in HTS windings in the motor are estimated and tested

  9. Systematic Evaluation of Methods for Integration of Transcriptomic Data into Constraint-Based Models of Metabolism

    DEFF Research Database (Denmark)

    Machado, Daniel; Herrgard, Markus

    2014-01-01

    of these methods has not been critically evaluated and compared. This work presents a survey of recently published methods that use transcript levels to try to improve metabolic flux predictions either by generating flux distributions or by creating context-specific models. A subset of these methods...... is then systematically evaluated using published data from three different case studies in E. coli and S. cerevisiae. The flux predictions made by different methods using transcriptomic data are compared against experimentally determined extracellular and intracellular fluxes (from 13C-labeling data). The sensitivity...... of the results to method-specific parameters is also evaluated, as well as their robustness to noise in the data. The results show that none of the methods outperforms the others for all cases. Also, it is observed that for many conditions, the predictions obtained by simple flux balance analysis using growth...

  10. Construction and analysis of the model of energy metabolism in E. coli.

    Directory of Open Access Journals (Sweden)

    Zixiang Xu

    Full Text Available Genome-scale models of metabolism have only been analyzed with the constraint-based modelling philosophy and there have been several genome-scale gene-protein-reaction models. But research on the modelling for energy metabolism of organisms just began in recent years and research on metabolic weighted complex network are rare in literature. We have made three research based on the complete model of E. coli's energy metabolism. We first constructed a metabolic weighted network using the rates of free energy consumption within metabolic reactions as the weights. We then analyzed some structural characters of the metabolic weighted network that we constructed. We found that the distribution of the weight values was uneven, that most of the weight values were zero while reactions with abstract large weight values were rare and that the relationship between w (weight values and v (flux values was not of linear correlation. At last, we have done some research on the equilibrium of free energy for the energy metabolism system of E. coli. We found that E(out (free energy rate input from the environment can meet the demand of E(ch(in (free energy rate dissipated by chemical process and that chemical process plays a great role in the dissipation of free energy in cells. By these research and to a certain extend, we can understand more about the energy metabolism of E. coli.

  11. A Mathematical Model of Metabolism and Regulation Provides a Systems-Level View of How Escherichia coli Responds to Oxygen

    Directory of Open Access Journals (Sweden)

    Michael eEderer

    2014-03-01

    Full Text Available The efficient redesign of bacteria for biotechnological purposes, such as biofuel production, waste disposal or specific biocatalytic functions, requires a quantitative systems-level understanding of energy supply, carbon and redox metabolism. The measurement of transcript levels, metabolite concentrations and metabolic fluxes per se gives an incomplete picture. An appreciation of the interdependencies between the different measurement values is essential for systems-level understanding. Mathematical modeling has the potential to provide a coherent and quantitative description of the interplay between gene expression, metabolite concentrations and metabolic fluxes. Escherichia coli undergoes major adaptations in central metabolism when the availability of oxygen changes. Thus, an integrated description of the oxygen response provides a benchmark of our understanding of carbon, energy and redox metabolism. We present the first comprehensive model of the central metabolism of E. coli that describes steady-state metabolism at different levels of oxygen availability. Variables of the model are metabolite concentrations, gene expression levels, transcription factor activities, metabolic fluxes and biomass concentration. We analyze the model with respect to the production capabilities of central metabolism of E. coli. In particular, we predict how precursor and biomass concentration are affected by product formation.

  12. DMPy: a Python package for automated mathematical model construction of large-scale metabolic systems.

    Science.gov (United States)

    Smith, Robert W; van Rosmalen, Rik P; Martins Dos Santos, Vitor A P; Fleck, Christian

    2018-06-19

    Models of metabolism are often used in biotechnology and pharmaceutical research to identify drug targets or increase the direct production of valuable compounds. Due to the complexity of large metabolic systems, a number of conclusions have been drawn using mathematical methods with simplifying assumptions. For example, constraint-based models describe changes of internal concentrations that occur much quicker than alterations in cell physiology. Thus, metabolite concentrations and reaction fluxes are fixed to constant values. This greatly reduces the mathematical complexity, while providing a reasonably good description of the system in steady state. However, without a large number of constraints, many different flux sets can describe the optimal model and we obtain no information on how metabolite levels dynamically change. Thus, to accurately determine what is taking place within the cell, finer quality data and more detailed models need to be constructed. In this paper we present a computational framework, DMPy, that uses a network scheme as input to automatically search for kinetic rates and produce a mathematical model that describes temporal changes of metabolite fluxes. The parameter search utilises several online databases to find measured reaction parameters. From this, we take advantage of previous modelling efforts, such as Parameter Balancing, to produce an initial mathematical model of a metabolic pathway. We analyse the effect of parameter uncertainty on model dynamics and test how recent flux-based model reduction techniques alter system properties. To our knowledge this is the first time such analysis has been performed on large models of metabolism. Our results highlight that good estimates of at least 80% of the reaction rates are required to accurately model metabolic systems. Furthermore, reducing the size of the model by grouping reactions together based on fluxes alters the resulting system dynamics. The presented pipeline automates the

  13. Model-based design of bistable cell factories for metabolic engineering.

    Science.gov (United States)

    Srinivasan, Shyam; Cluett, William R; Mahadevan, Radhakrishnan

    2018-04-15

    Metabolism can exhibit dynamic phenomena like bistability due to the presence of regulatory motifs like the positive feedback loop. As cell factories, microorganisms with bistable metabolism can have a high and a low product flux at the two stable steady states, respectively. The exclusion of metabolic regulation and network dynamics limits the ability of pseudo-steady state stoichiometric models to detect the presence of bistability, and reliably assess the outcomes of design perturbations to metabolic networks. Using kinetic models of metabolism, we assess the change in the bistable characteristics of the network, and suggest designs based on perturbations to the positive feedback loop to enable the network to produce at its theoretical maximum rate. We show that the most optimal production design in parameter space, for a small bistable metabolic network, may exist at the boundary of the bistable region separating it from the monostable region of low product fluxes. The results of our analysis can be broadly applied to other bistable metabolic networks with similar positive feedback network topologies. This can complement existing model-based design strategies by providing a smaller number of feasible designs that need to be tested in vivo. http://lmse.biozone.utoronto.ca/downloads/. krishna.mahadevan@utoronto.ca. Supplementary data are available at Bioinformatics online.

  14. Probing the Importance of Charge Flux in Force Field Modeling.

    Science.gov (United States)

    Sedghamiz, Elaheh; Nagy, Balazs; Jensen, Frank

    2017-08-08

    We analyze the conformational dependence of atomic charges and molecular dipole moments for a selection of ∼900 conformations of peptide models of the 20 neutral amino acids. Based on a set of reference density functional theory calculations, we partition the changes into effects due to changes in bond distances, bond angles, and torsional angles and into geometry and charge flux contributions. This allows an assessment of the limitations of fixed charge force fields and indications for how to design improved force fields. The torsional degrees of freedom are the main contribution to conformational changes of atomic charges and molecular dipole moments, but indirect effects due to change in bond distances and angles account for ∼25% of the variation. Charge flux effects dominate for changes in bond distances and are also the main component of the variation in bond angles, while they are ∼25% compared to the geometry variations for torsional degrees of freedom. The geometry and charge flux contributions to some extent produce compensating effects.

  15. Global Bedload Flux Modeling and Analysis in Large Rivers

    Science.gov (United States)

    Islam, M. T.; Cohen, S.; Syvitski, J. P.

    2017-12-01

    Proper sediment transport quantification has long been an area of interest for both scientists and engineers in the fields of geomorphology, and management of rivers and coastal waters. Bedload flux is important for monitoring water quality and for sustainable development of coastal and marine bioservices. Bedload measurements, especially for large rivers, is extremely scarce across time, and many rivers have never been monitored. Bedload measurements in rivers, is particularly acute in developing countries where changes in sediment yields is high. The paucity of bedload measurements is the result of 1) the nature of the problem (large spatial and temporal uncertainties), and 2) field costs including the time-consuming nature of the measurement procedures (repeated bedform migration tracking, bedload samplers). Here we present a first of its kind methodology for calculating bedload in large global rivers (basins are >1,000 km. Evaluation of model skill is based on 113 bedload measurements. The model predictions are compared with an empirical model developed from the observational dataset in an attempt to evaluate the differences between a physically-based numerical model and a lumped relationship between bedload flux and fluvial and basin parameters (e.g., discharge, drainage area, lithology). The initial study success opens up various applications to global fluvial geomorphology (e.g. including the relationship between suspended sediment (wash load) and bedload). Simulated results with known uncertainties offers a new research product as a valuable resource for the whole scientific community.

  16. Revealing differences in metabolic flux distributions between a mutant strain and its parent strain Gluconacetobacter xylinus CGMCC 2955.

    Directory of Open Access Journals (Sweden)

    Cheng Zhong

    Full Text Available A better understanding of metabolic fluxes is important for manipulating microbial metabolism toward desired end products, or away from undesirable by-products. A mutant strain, Gluconacetobacter xylinus AX2-16, was obtained by combined chemical mutation of the parent strain (G. xylinus CGMCC 2955 using DEC (diethyl sulfate and LiCl. The highest bacterial cellulose production for this mutant was obtained at about 11.75 g/L, which was an increase of 62% compared with that by the parent strain. In contrast, gluconic acid (the main byproduct concentration was only 5.71 g/L for mutant strain, which was 55.7% lower than that of parent strain. Metabolic flux analysis indicated that 40.1% of the carbon source was transformed to bacterial cellulose in mutant strain, compared with 24.2% for parent strain. Only 32.7% and 4.0% of the carbon source were converted into gluconic acid and acetic acid in mutant strain, compared with 58.5% and 9.5% of that in parent strain. In addition, a higher flux of tricarboxylic acid (TCA cycle was obtained in mutant strain (57.0% compared with parent strain (17.0%. It was also indicated from the flux analysis that more ATP was produced in mutant strain from pentose phosphate pathway (PPP and TCA cycle. The enzymatic activity of succinate dehydrogenase (SDH, which is one of the key enzymes in TCA cycle, was 1.65-fold higher in mutant strain than that in parent strain at the end of culture. It was further validated by the measurement of ATPase that 3.53-6.41 fold higher enzymatic activity was obtained from mutant strain compared with parent strain.

  17. Annual benthic metabolism and organic carbon fluxes in a semi-enclosed Mediterranean bay dominated by the macroalgae Caulerpa prolifera.

    Directory of Open Access Journals (Sweden)

    Sergio eRuiz-Halpern

    2014-12-01

    Full Text Available Coastal areas play an important role on carbon cycling. Elucidating the dynamics on the production, transport and fate of organic carbon is relevant to gain a better understanding of the role coastal areas play in the global carbon budget. Here, we assess the metabolic status and associated organic carbon fluxes of a semi-enclosed Mediterranean bay supporting a meadow of Caulerpa prolifera. We test whether the EDOC pool is a significant component of the organic carbon pool and associated fluxes in this ecosystem. The Bay of Portocolom was in net metabolic balance on a yearly basis, but heterotrophic during the summer months. Community respiration (CR was positively correlated to C. prolifera biomass, while net community production (NCP had a negative correlation. The benthic compartment represented, on average, 72.6 ± 5.2 % of CR and 86.8 ± 4.5 % of gross primary production (GPP. Dissolved organic carbon (DOC production peaked in summer and was always positive, with the incubations performed in the dark almost doubling the flux of those performed in the light. Exchangeable dissolved organic carbon (EDOC, however, oscillated between production and uptake, being completely recycled within the system and representing around 14% of the DOC flux. The pools of bottom and surface DOC were high for an oligotrophic environment, and were positively correlated to the pool of EDOC. Thus, despite being in metabolic balance, this ecosystem acted as a conduit for organic carbon (OC, as it is able to export OC to adjacent areas derived from allochtonous inputs during heterotrophic conditions. These inputs likely come from groundwater discharge, human activity in the watershed, delivered to the sediments through the high capacity of C. prolifera to remove particles from the water column, and from the air-water exchange of EDOC, demonstrating that these communities are a major contributor to the cycling of OC in coastal embayments.

  18. Community metabolism and air-sea CO[sub 2] fluxes in a coral reef ecosystem (Moorea, French Polynesia)

    Energy Technology Data Exchange (ETDEWEB)

    Gattuso, J P; Pichon, M; Delesalle, B; Frankignoulle, M [Observatory of European Oceanology (Monaco)

    1993-06-01

    Community metabolism (primary production, respiration and calcification) and air-sea CO[sub 2] fluxes of the 'Tiahura barrier reef' (Moorea, French Polynesia) were investigated in November and December 1991. Gross production and respiration were respectively 640.2 to 753 and 590.4 to 641.5 mmol (O[sub 2] or CO[sub 2]) m[sup 2] d[sup -1] (7.7 to 9.0 and 7.1 to 7.7 g C m)[sup 2] d[sup -1] and the reef displayed a slightly negative excess (net) production. The contribution of planktonic primary production to reef metabolism was negligible (0.15% of total gross production). Net calcification was positive both during the day and at night; its daily value was 243 mmol CaCO[sub 3] m[sup 2] d[sup -1] (24.3 g CaCO)[sub 3] m[sup -2] d[sup -1]. Reef metabolism decreased seawater total CO[sub 2] by 433.3 mmol m[sup 2] d[sup -1]. The air-sea CO[sub 2] fluxes were close to zero in the ocean but displayed a strong daily pattern at the reef front and the back reef. Fluxes were positive (CO[sub 2] evasion) at night, decreased as irradiance increased and were negative during the day (CO[sub 2] invasion). Integration of the fluxes measured during a 24 h experiment at the back reef showed that the reef was a source of CO[sub 2] to the atmosphere (1.5 mmol m[sup 2] d[sup -1]).

  19. C-13 Tracer experiments and metabolite balancing for metabolic flux analysis

    DEFF Research Database (Denmark)

    Schmidt, Karsten; Marx, A.; de Graaf, A. A.

    1998-01-01

    performed independently for a wild-type strain of Aspergillus oryzae producing alpha-amylase. Two different nitrogen sources, NH4+ and NO3-, have been used to investigate the influence of the NADPH requirements on the intracellular flux distribution. The two different approaches to the calculation of fluxes...

  20. Modeling of Local Magnetic Field Enhancements within Solar Flux Ropes

    OpenAIRE

    Romashets, E; Vandas, M; Poedts, Stefaan

    2010-01-01

    To model and study local magnetic-field enhancements in a solar flux rope we consider the magnetic field in its interior as a superposition of two linear (constant alpha) force-free magnetic-field distributions, viz. a global one, which is locally similar to a part of the cylinder, and a local torus-shaped magnetic distribution. The newly derived solution for a toroid with an aspect ratio close to unity is applied. The symmetry axis of the toroid and that of the cylinder may or may not coinci...

  1. Local models of heterotic flux vacua: spacetime and worldsheet aspects

    International Nuclear Information System (INIS)

    Israel, D.; Carlevaro, L.

    2011-01-01

    We report on some recent progress in understanding heterotic flux compactifications, from a worldsheet perspective mainly. We consider local models consisting in torus fibration over warped Eguchi-Hanson space and non-Kaehler resolved conifold geometries. We analyze the supergravity solutions and define a double-scaling limit of the resolved singularities, defined such that the geometry is smooth and weakly coupled. We show that, remarkably, the heterotic solutions admit solvable worldsheet CFT descriptions in this limit. This allows in particular to understand the important role of worldsheet non-perturbative effects. (Copyright copyright 2011 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim)

  2. Numerical cell model investigating cellular carbon fluxes in Emiliania huxleyi.

    Science.gov (United States)

    Holtz, Lena-Maria; Wolf-Gladrow, Dieter; Thoms, Silke

    2015-01-07

    Coccolithophores play a crucial role in the marine carbon cycle and thus it is interesting to know how they will respond to climate change. After several decades of research the interplay between intracellular processes and the marine carbonate system is still not well understood. On the basis of experimental findings given in literature, a numerical cell model is developed that describes inorganic carbon fluxes between seawater and the intracellular sites of calcite precipitation and photosynthetic carbon fixation. The implemented cell model consists of four compartments, for each of which the carbonate system is resolved individually. The four compartments are connected to each other via H(+), CO2, and HCO3(-) fluxes across the compartment-confining membranes. For CO2 accumulation around RubisCO, an energy-efficient carbon concentrating mechanism is proposed that relies on diffusive CO2 uptake. At low external CO2 concentrations and high light intensities, CO2 diffusion does not suffice to cover the carbon demand of photosynthesis and an additional uptake of external HCO3(-) becomes essential. The model is constrained by data of Emiliania huxleyi, the numerically most abundant coccolithophore species in the present-day ocean. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

  3. Control of fluxes towards antibiotics and the role of primary metabolism in production of antibiotics

    DEFF Research Database (Denmark)

    Gunnarsson, Nina; Eliasson Lantz, Anna; Nielsen, Jacob

    2004-01-01

    Yield improvements in antibiotic-producing strains have classically been obtained through random mutagenesis and screening. An attractive alternative to this strategy is the rational design of producer strains via metabolic engineering, an approach that offers the possibility to increase yields...... in the metabolic network. Here we describe and discuss available methods for identification of these steps, both in antibiotic biosynthesis pathways and in the primary metabolism, which serves as the supplier of precursors and cofactors for the secondary metabolism. Finally, the importance of precursor...... and cofactor supply from primary metabolism in the biosynthesis of different types of antibiotics is discussed and recent developments in metabolic engineering towards increased product yields in antibiotic producing strains are reviewed....

  4. Carbon-flux distribution within Streptomyces coelicolor metabolism: a comparison between the actinorhodin-producing strain M145 and its non-producing derivative M1146.

    Directory of Open Access Journals (Sweden)

    Fabien Coze

    Full Text Available Metabolic Flux Analysis is now viewed as essential to elucidate the metabolic pattern of cells and to design appropriate genetic engineering strategies to improve strain performance and production processes. Here, we investigated carbon flux distribution in two Streptomyces coelicolor A3 (2 strains: the wild type M145 and its derivative mutant M1146, in which gene clusters encoding the four main antibiotic biosynthetic pathways were deleted. Metabolic Flux Analysis and (13C-labeling allowed us to reconstruct a flux map under steady-state conditions for both strains. The mutant strain M1146 showed a higher growth rate, a higher flux through the pentose phosphate pathway and a higher flux through the anaplerotic phosphoenolpyruvate carboxylase. In that strain, glucose uptake and the flux through the Krebs cycle were lower than in M145. The enhanced flux through the pentose phosphate pathway in M1146 is thought to generate NADPH enough to face higher needs for biomass biosynthesis and other processes. In both strains, the production of NADPH was higher than NADPH needs, suggesting a key role for nicotinamide nucleotide transhydrogenase for redox homeostasis. ATP production is also likely to exceed metabolic ATP needs, indicating that ATP consumption for maintenance is substantial.Our results further suggest a possible competition between actinorhodin and triacylglycerol biosynthetic pathways for their common precursor, acetyl-CoA. These findings may be instrumental in developing new strategies exploiting S. coelicolor as a platform for the production of bio-based products of industrial interest.

  5. Dynamic Metabolic Model Building Based on the Ensemble Modeling Approach

    Energy Technology Data Exchange (ETDEWEB)

    Liao, James C. [Univ. of California, Los Angeles, CA (United States)

    2016-10-01

    Ensemble modeling of kinetic systems addresses the challenges of kinetic model construction, with respect to parameter value selection, and still allows for the rich insights possible from kinetic models. This project aimed to show that constructing, implementing, and analyzing such models is a useful tool for the metabolic engineering toolkit, and that they can result in actionable insights from models. Key concepts are developed and deliverable publications and results are presented.

  6. MCT1 and MCT4 expression and lactate flux activity increase during white and brown adipogenesis and impact adipocyte metabolism

    DEFF Research Database (Denmark)

    Petersen, Charlotte; Nielsen, Mette D.; Andersen, Elise S.

    2017-01-01

    RNA and protein levels of the lactate-H+ transporter MCT1 and the Na+,HCO3 - cotransporter NBCe1 were upregulated in mouse interscapular brown and inguinal white adipose tissue upon cold induction of thermogenesis and browning. MCT1, MCT4, and NBCe1 were furthermore strongly upregulated at the mRNA and protein...... level upon differentiation of cultured pre-adipocytes. Adipocyte differentiation was accompanied by increased plasma membrane lactate flux capacity, which was reduced by MCT inhibition and by MCT1 knockdown. Finally, in differentiated brown adipocytes, glycolysis (assessed as ECAR), and after...... noradrenergic stimulation also oxidative metabolism (OCR), was decreased by MCT inhibition. We suggest that upregulation of MCT1- and MCT4-mediated lactate flux capacity and NBCe1-mediated HCO3 -/pH homeostasis are important for the physiological function of mature adipocytes....

  7. In silico strain optimization by adding reactions to metabolic models.

    Science.gov (United States)

    Correia, Sara; Rocha, Miguel

    2012-07-24

    Nowadays, the concerns about the environment and the needs to increase the productivity at low costs, demand for the search of new ways to produce compounds with industrial interest. Based on the increasing knowledge of biological processes, through genome sequencing projects, and high-throughput experimental techniques as well as the available computational tools, the use of microorganisms has been considered as an approach to produce desirable compounds. However, this usually requires to manipulate these organisms by genetic engineering and/ or changing the enviromental conditions to make the production of these compounds possible. In many cases, it is necessary to enrich the genetic material of those microbes with hereologous pathways from other species and consequently adding the potential to produce novel compounds. This paper introduces a new plug-in for the OptFlux Metabolic Engineering platform, aimed at finding suitable sets of reactions to add to the genomes of selected microbes (wild type strain), as well as finding complementary sets of deletions, so that the mutant becomes able to overproduce compounds with industrial interest, while preserving their viability. The necessity of adding reactions to the metabolic model arises from existing gaps in the original model or motivated by the productions of new compounds by the organism. The optimization methods used are metaheuristics such as Evolutionary Algorithms and Simulated Annealing. The usefulness of this plug-in is demonstrated by a case study, regarding the production of vanillin by the bacterium E. coli.

  8. Computational Modelling of the Metabolic States Regulated by the Kinase Akt

    Directory of Open Access Journals (Sweden)

    Ettore eMosca

    2012-11-01

    Full Text Available Signal transduction pathways and gene regulation determine a major reorganization of metabolic activities in order to support cell proliferation. Protein Kinase B (PKB, also known as Akt, participates in the PI3K/Akt/mTOR pathway, a master regulator of aerobic glycolysis and cellular biosynthesis, two activities shown by both normal and cancer proliferating cells. Not surprisingly considering its relevance for cellular metabolism, Akt/PKB is often found hyperactive in cancer cells. In the last decade, many efforts have been made to improve the understanding of the control of glucose metabolism and the identification of a therapeutic window between proliferating cancer cells and proliferating normal cells. In this context, we have modelled the link between the PI3K/Akt/mTOR pathway, glycolysis, lactic acid production and nucleotide biosynthesis. We used a computational model in order to compare two metabolic states generated by the specific variation of the metabolic fluxes regulated by the activity of the PI3K/Akt/mTOR pathway. One of the two states represented the metabolism of a growing cancer cell characterised by aerobic glycolysis and cellular biosynthesis, while the other state represented the same metabolic network with a reduced glycolytic rate and a higher mitochondrial pyruvate metabolism, as reported in literature in relation to the activity of the PI3K/Akt/mTOR. Some steps that link glycolysis and pentose phosphate pathway revealed their importance for controlling the dynamics of cancer glucose metabolism.

  9. Modelling neutrino and gamma-ray fluxes in supernova remnants

    International Nuclear Information System (INIS)

    Ballet, J; Cassam-Chenai, G; Maurin, G; Naumann, C

    2008-01-01

    Supernova remnants (SNRs) are believed to accelerate charged particles by diffusive shock acceleration (DSA) and to produce the majority of galactic cosmic rays, at least up to the 'knee' at 3-10 15 electron volts. In the framework of a hydrodynamic self-similar simulation of the evolution of young supernova remnants, its interaction with the ambient matter as well as the microwave and infrared background is studied. The photon spectra resulting from synchrotron and inverse Compton emission as well as from hadronic processes are calculated, as are the accompanying neutrino fluxes. Applying this method to the particular case of the SNR RXJ-1713, 7-3946, we find that its TeV emission can in principle be explained by pion decay if the ambient density is assumed to grow with increasing distance from the centre. The neutrino flux associated with this hadronic model is of a magnitude that may be detectable by a cubic-kilometre sized deep-sea neutrino telescope in the northern hemisphere. In this poster, a description of the supernova remnant simulation is given together with the results concerning RXJ-1713.

  10. High Flux Isotope Reactor system RELAP5 input model

    International Nuclear Information System (INIS)

    Morris, D.G.; Wendel, M.W.

    1993-01-01

    A thermal-hydraulic computational model of the High Flux Isotope Reactor (HFIR) has been developed using the RELAP5 program. The purpose of the model is to provide a state-of-the art thermal-hydraulic simulation tool for analyzing selected hypothetical accident scenarios for a revised HFIR Safety Analysis Report (SAR). The model includes (1) a detailed representation of the reactor core and other vessel components, (2) three heat exchanger/pump cells, (3) pressurizing pumps and letdown valves, and (4) secondary coolant system (with less detail than the primary system). Data from HFIR operation, component tests, tests in facility mockups and the HFIR, HFIR specific experiments, and other pertinent experiments performed independent of HFIR were used to construct the model and validate it to the extent permitted by the data. The detailed version of the model has been used to simulate loss-of-coolant accidents (LOCAs), while the abbreviated version has been developed for the operational transients that allow use of a less detailed nodalization. Analysis of station blackout with core long-term decay heat removal via natural convection has been performed using the core and vessel portions of the detailed model

  11. Electron Flux Models for Different Energies at Geostationary Orbit

    Science.gov (United States)

    Boynton, R. J.; Balikhin, M. A.; Sibeck, D. G.; Walker, S. N.; Billings, S. A.; Ganushkina, N.

    2016-01-01

    Forecast models were derived for energetic electrons at all energy ranges sampled by the third-generation Geostationary Operational Environmental Satellites (GOES). These models were based on Multi-Input Single-Output Nonlinear Autoregressive Moving Average with Exogenous inputs methodologies. The model inputs include the solar wind velocity, density and pressure, the fraction of time that the interplanetary magnetic field (IMF) was southward, the IMF contribution of a solar wind-magnetosphere coupling function proposed by Boynton et al. (2011b), and the Dst index. As such, this study has deduced five new 1 h resolution models for the low-energy electrons measured by GOES (30-50 keV, 50-100 keV, 100-200 keV, 200-350 keV, and 350-600 keV) and extended the existing >800 keV and >2 MeV Geostationary Earth Orbit electron fluxes models to forecast at a 1 h resolution. All of these models were shown to provide accurate forecasts, with prediction efficiencies ranging between 66.9% and 82.3%.

  12. Expanding a dynamic flux balance model of yeast fermentation to genome-scale

    Science.gov (United States)

    2011-01-01

    Background Yeast is considered to be a workhorse of the biotechnology industry for the production of many value-added chemicals, alcoholic beverages and biofuels. Optimization of the fermentation is a challenging task that greatly benefits from dynamic models able to accurately describe and predict the fermentation profile and resulting products under different genetic and environmental conditions. In this article, we developed and validated a genome-scale dynamic flux balance model, using experimentally determined kinetic constraints. Results Appropriate equations for maintenance, biomass composition, anaerobic metabolism and nutrient uptake are key to improve model performance, especially for predicting glycerol and ethanol synthesis. Prediction profiles of synthesis and consumption of the main metabolites involved in alcoholic fermentation closely agreed with experimental data obtained from numerous lab and industrial fermentations under different environmental conditions. Finally, fermentation simulations of genetically engineered yeasts closely reproduced previously reported experimental results regarding final concentrations of the main fermentation products such as ethanol and glycerol. Conclusion A useful tool to describe, understand and predict metabolite production in batch yeast cultures was developed. The resulting model, if used wisely, could help to search for new metabolic engineering strategies to manage ethanol content in batch fermentations. PMID:21595919

  13. A statistical model for horizontal mass flux of erodible soil

    International Nuclear Information System (INIS)

    Babiker, A.G.A.G.; Eltayeb, I.A.; Hassan, M.H.A.

    1986-11-01

    It is shown that the mass flux of erodible soil transported horizontally by a statistically distributed wind flow has a statistical distribution. Explicit expression for the probability density function, p.d.f., of the flux is derived for the case in which the wind speed has a Weibull distribution. The statistical distribution for a mass flux characterized by a generalized Bagnold formula is found to be Weibull for the case of zero threshold speed. Analytic and numerical values for the average horizontal mass flux of soil are obtained for various values of wind parameters, by evaluating the first moment of the flux density function. (author)

  14. Genome-scale metabolic modeling of Mucor circinelloides and comparative analysis with other oleaginous species.

    Science.gov (United States)

    Vongsangnak, Wanwipa; Klanchui, Amornpan; Tawornsamretkit, Iyarest; Tatiyaborwornchai, Witthawin; Laoteng, Kobkul; Meechai, Asawin

    2016-06-01

    We present a novel genome-scale metabolic model iWV1213 of Mucor circinelloides, which is an oleaginous fungus for industrial applications. The model contains 1213 genes, 1413 metabolites and 1326 metabolic reactions across different compartments. We demonstrate that iWV1213 is able to accurately predict the growth rates of M. circinelloides on various nutrient sources and culture conditions using Flux Balance Analysis and Phenotypic Phase Plane analysis. Comparative analysis of three oleaginous genome-scale models, including M. circinelloides (iWV1213), Mortierella alpina (iCY1106) and Yarrowia lipolytica (iYL619_PCP) revealed that iWV1213 possesses a higher number of genes involved in carbohydrate, amino acid, and lipid metabolisms that might contribute to its versatility in nutrient utilization. Moreover, the identification of unique and common active reactions among the Zygomycetes oleaginous models using Flux Variability Analysis unveiled a set of gene/enzyme candidates as metabolic engineering targets for cellular improvement. Thus, iWV1213 offers a powerful metabolic engineering tool for multi-level omics analysis, enabling strain optimization as a cell factory platform of lipid-based production. Copyright © 2016 Elsevier B.V. All rights reserved.

  15. Comparison of CME radial velocities from a flux rope model and an ice cream cone model

    Science.gov (United States)

    Kim, T.; Moon, Y.; Na, H.

    2011-12-01

    Coronal Mass Ejections (CMEs) on the Sun are the largest energy release process in the solar system and act as the primary driver of geomagnetic storms and other space weather phenomena on the Earth. So it is very important to infer their directions, velocities and three-dimensional structures. In this study, we choose two different models to infer radial velocities of halo CMEs since 2008 : (1) an ice cream cone model by Xue et al (2005) using SOHO/LASCO data, (2) a flux rope model by Thernisien et al. (2009) using the STEREO/SECCHI data. In addition, we use another flux rope model in which the separation angle of flux rope is zero, which is morphologically similar to the ice cream cone model. The comparison shows that the CME radial velocities from among each model have very good correlations (R>0.9). We will extending this comparison to other partial CMEs observed by STEREO and SOHO.

  16. Thermodynamic analysis of regulation in metabolic networks using constraint-based modeling

    Directory of Open Access Journals (Sweden)

    Mahadevan Radhakrishnan

    2010-05-01

    Full Text Available Abstract Background Geobacter sulfurreducens is a member of the Geobacter species, which are capable of oxidation of organic waste coupled to the reduction of heavy metals and electrode with applications in bioremediation and bioenergy generation. While the metabolism of this organism has been studied through the development of a stoichiometry based genome-scale metabolic model, the associated regulatory network has not yet been well studied. In this manuscript, we report on the implementation of a thermodynamics based metabolic flux model for Geobacter sulfurreducens. We use this updated model to identify reactions that are subject to regulatory control in the metabolic network of G. sulfurreducens using thermodynamic variability analysis. Findings As a first step, we have validated the regulatory sites and bottleneck reactions predicted by the thermodynamic flux analysis in E. coli by evaluating the expression ranges of the corresponding genes. We then identified ten reactions in the metabolic network of G. sulfurreducens that are predicted to be candidates for regulation. We then compared the free energy ranges for these reactions with the corresponding gene expression fold changes under conditions of different environmental and genetic perturbations and show that the model predictions of regulation are consistent with data. In addition, we also identify reactions that operate close to equilibrium and show that the experimentally determined exchange coefficient (a measure of reversibility is significant for these reactions. Conclusions Application of the thermodynamic constraints resulted in identification of potential bottleneck reactions not only from the central metabolism but also from the nucleotide and amino acid subsystems, thereby showing the highly coupled nature of the thermodynamic constraints. In addition, thermodynamic variability analysis serves as a valuable tool in estimating the ranges of ΔrG' of every reaction in the model

  17. GEM-CEDAR Challenge: Poynting Flux at DMSP and Modeled Joule Heat

    Science.gov (United States)

    Rastaetter, Lutz; Shim, Ja Soon; Kuznetsova, Maria M.; Kilcommons, Liam M.; Knipp, Delores J.; Codrescu, Mihail; Fuller-Rowell, Tim; Emery, Barbara; Weimer, Daniel R.; Cosgrove, Russell; hide

    2016-01-01

    Poynting flux into the ionosphere measures the electromagnetic energy coming from the magnetosphere. This energy flux can vary greatly between quiet times and geomagnetic active times. As part of the Geospace Environment Modeling-coupling energetics and dynamics of atmospheric regions modeling challenge, physics-based models of the 3-D ionosphere and ionospheric electrodynamics solvers of magnetosphere models that specify Joule heat and empirical models specifying Poynting flux were run for six geomagnetic storm events of varying intensity. We compared model results with Poynting flux values along the DMSP-15 satellite track computed from ion drift meter and magnetic field observations. Although being a different quantity, Joule heat can in practice be correlated to incoming Poynting flux because the energy is dissipated primarily in high latitudes where Poynting flux is being deposited. Within the physics-based model group, we find mixed results with some models overestimating Joule heat and some models agreeing better with observed Poynting flux rates as integrated over auroral passes. In contrast, empirical models tend to underestimate integrated Poynting flux values. Modeled Joule heat or Poynting flux patterns often resemble the observed Poynting flux patterns on a large scale, but amplitudes can differ by a factor of 2 or larger due to the highly localized nature of observed Poynting flux deposition that is not captured by the models. In addition, the positioning of modeled patterns appear to be randomly shifted against the observed Poynting flux energy input. This study is the first to compare Poynting flux and Joule heat in a large variety of models of the ionosphere.

  18. Using Lunar Impact Basin Relaxation to Test Impact Flux Models

    Science.gov (United States)

    Nimmo, F.; Conrad, J. W.; Neumann, G. A.; Kamata, S.; Fassett, C.

    2017-12-01

    Gravity data obtained by the GRAIL mission [1] has constrained the number and distribution of lunar impact basins [2]. We analyzed crater densities for newly-proposed basins to assign relative ages. The extent to which a basin is relaxed is calculated using GRAIL-derived crustal thickness models [3] by comparing the mantle uplift under basins to the surrounding region. With our catalog we can investigate the distribution of basin properties through relative time. We identify a relaxation state transition (RT) around the pre-Nectarian 4 relative age group for basins with diameters > 450 km, similar to previous results using a pre-GRAIL basin catalog [4]. This RT likely signals a change in the global thermal state of the crust, representing the time at which the lunar moho temperature fell below 1400 K [4]. This transition happens 50-100 million years (Myr) after the lunar magma ocean (LMO) solidifies [4]. Based on models and inferences of LMO solidification [5, 6] the RT is expected to occur at 4.25-4.50 Ga, depending on the rate of cooling once a crustal lid has formed [5] and the amount of tidal heating in the early crust [6]. Monotonically declining impact flux models, such as [7] and [8] predict a younger RT; 4.07-4.08 and 4.24-4.27 Ga respectively. A scaled-down version of [8] can fit the RT but fails to match the observed number of younger, unrelaxed basins. Models that invoke a later transient increase in impact flux can reproduce the inferred RT time; for instance, the model of [9] gives a RT age of 4.43-4.46 Ga. This model matches the number of younger basins and implies that basin preservation started at 4.49 Ga, likely before the LMO completely solidified. [1] Zuber M.T. et al. (2013) Science, 339, 668-671. [2] Neumann G.A. et al. (2015) Science Advances, 1, e1500852. [3] Wieczorek M.A. (2013) Science, 339, 671-675. [4] Kamata S. et al. (2015) Icarus, 250, 492-504. [5] Elkins-Tanton L.T. et al. (2011) Earth Planet. Sci. Lett., 304, 326-336. [6] Meyer, J

  19. Linearized Flux Evolution (LiFE): A technique for rapidly adapting fluxes from full-physics radiative transfer models

    Science.gov (United States)

    Robinson, Tyler D.; Crisp, David

    2018-05-01

    Solar and thermal radiation are critical aspects of planetary climate, with gradients in radiative energy fluxes driving heating and cooling. Climate models require that radiative transfer tools be versatile, computationally efficient, and accurate. Here, we describe a technique that uses an accurate full-physics radiative transfer model to generate a set of atmospheric radiative quantities which can be used to linearly adapt radiative flux profiles to changes in the atmospheric and surface state-the Linearized Flux Evolution (LiFE) approach. These radiative quantities describe how each model layer in a plane-parallel atmosphere reflects and transmits light, as well as how the layer generates diffuse radiation by thermal emission and by scattering light from the direct solar beam. By computing derivatives of these layer radiative properties with respect to dynamic elements of the atmospheric state, we can then efficiently adapt the flux profiles computed by the full-physics model to new atmospheric states. We validate the LiFE approach, and then apply this approach to Mars, Earth, and Venus, demonstrating the information contained in the layer radiative properties and their derivatives, as well as how the LiFE approach can be used to determine the thermal structure of radiative and radiative-convective equilibrium states in one-dimensional atmospheric models.

  20. SU-G-TeP3-10: Radiation Induces Prompt Live-Cell Metabolic Fluxes

    Energy Technology Data Exchange (ETDEWEB)

    Campos, D [University of Wisconsin Madison, Madison, WI (United States); Peeters, W; Bussink, J [Radboud University Medical Center, Nijmegen, GA (United States); Nickel, K [University of Wisconsin - Madison, Madison, Wisconsin (United States); Burkel, B; Kimple, R; Kogel, A van der; Eliceiri, K [University of Wisconsin - Madison, Madison, WI (United States); Kissick, M [University of Wisconsin, Madison, WI (United States)

    2016-06-15

    Purpose: To compare metabolic dynamics and HIF-1α expression following radiation between a cancerous cell line (UM-SCC-22B) and a normal, immortalized cell line, NOK (Normal Oral Keratinocyte). HIF-1 is a key factor in metabolism and radiosensitivity. A better understanding of how radiation affects the interplay of metabolism and HIF-1 might give a better understanding of the mechanisms responsible for radiosensitivity. Methods: Changes in cellular metabolism in response to radiation are tracked by fluorescence lifetime of NADH. Expression of HIF-1α was measured by immunofluorescence for both cell lines with and without irradiation. Radiation response is also monitored with additional treatment of a HIF-1α inhibitor (chrysin) as well as a radical scavenger (glutathione). Changes in oxygen consumption and respiratory capacity are also monitored using the Seahorse XF analyzer. Results: An increase in HIF-1α was found to be in response to radiation for the cancer cell line, but not the normal cell line. Radiation was found to shift metabolism toward glycolytic pathways in cancer cells as measured by oxygen consumption and respiratory capacity. Radiation response was found to be muted by addition of glutathione to cell media. HIF-1α inhibition similarly muted radiation response in cancer. Conclusion: The HIF-1 protein complex is a key regulator cellular metabolism through the regulation of glycolysis and glucose transport enzymes. Moreover, HIF-1 has shown radio-protective effects in tumor vascular endothelia, and has been implicated in metastatic aggression. Monitoring interplay between metabolism and the HIF-1 protein complex can give a more fundamental understanding of radiotherapy response.

  1. SU-G-TeP3-10: Radiation Induces Prompt Live-Cell Metabolic Fluxes

    International Nuclear Information System (INIS)

    Campos, D; Peeters, W; Bussink, J; Nickel, K; Burkel, B; Kimple, R; Kogel, A van der; Eliceiri, K; Kissick, M

    2016-01-01

    Purpose: To compare metabolic dynamics and HIF-1α expression following radiation between a cancerous cell line (UM-SCC-22B) and a normal, immortalized cell line, NOK (Normal Oral Keratinocyte). HIF-1 is a key factor in metabolism and radiosensitivity. A better understanding of how radiation affects the interplay of metabolism and HIF-1 might give a better understanding of the mechanisms responsible for radiosensitivity. Methods: Changes in cellular metabolism in response to radiation are tracked by fluorescence lifetime of NADH. Expression of HIF-1α was measured by immunofluorescence for both cell lines with and without irradiation. Radiation response is also monitored with additional treatment of a HIF-1α inhibitor (chrysin) as well as a radical scavenger (glutathione). Changes in oxygen consumption and respiratory capacity are also monitored using the Seahorse XF analyzer. Results: An increase in HIF-1α was found to be in response to radiation for the cancer cell line, but not the normal cell line. Radiation was found to shift metabolism toward glycolytic pathways in cancer cells as measured by oxygen consumption and respiratory capacity. Radiation response was found to be muted by addition of glutathione to cell media. HIF-1α inhibition similarly muted radiation response in cancer. Conclusion: The HIF-1 protein complex is a key regulator cellular metabolism through the regulation of glycolysis and glucose transport enzymes. Moreover, HIF-1 has shown radio-protective effects in tumor vascular endothelia, and has been implicated in metastatic aggression. Monitoring interplay between metabolism and the HIF-1 protein complex can give a more fundamental understanding of radiotherapy response.

  2. Investigating host-pathogen behavior and their interaction using genome-scale metabolic network models.

    Science.gov (United States)

    Sadhukhan, Priyanka P; Raghunathan, Anu

    2014-01-01

    Genome Scale Metabolic Modeling methods represent one way to compute whole cell function starting from the genome sequence of an organism and contribute towards understanding and predicting the genotype-phenotype relationship. About 80 models spanning all the kingdoms of life from archaea to eukaryotes have been built till date and used to interrogate cell phenotype under varying conditions. These models have been used to not only understand the flux distribution in evolutionary conserved pathways like glycolysis and the Krebs cycle but also in applications ranging from value added product formation in Escherichia coli to predicting inborn errors of Homo sapiens metabolism. This chapter describes a protocol that delineates the process of genome scale metabolic modeling for analysing host-pathogen behavior and interaction using flux balance analysis (FBA). The steps discussed in the process include (1) reconstruction of a metabolic network from the genome sequence, (2) its representation in a precise mathematical framework, (3) its translation to a model, and (4) the analysis using linear algebra and optimization. The methods for biological interpretations of computed cell phenotypes in the context of individual host and pathogen models and their integration are also discussed.

  3. Modelling of recharge and pollutant fluxes to urban groundwaters

    International Nuclear Information System (INIS)

    Thomas, Abraham; Tellam, John

    2006-01-01

    Urban groundwater resources are of considerable importance to the long-term viability of many cities world-wide, yet prediction of the quantity and quality of recharge is only rarely attempted at anything other than a very basic level. This paper describes the development of UGIf, a simple model written within a GIS, designed to provide estimates of spatially distributed recharge and recharge water quality in unconfined but covered aquifers. The following processes (with their calculation method indicated) are included: runoff and interception (curve number method); evapotranspiration (Penman-Grindley); interflow (empirical index approach); volatilization (Henry's law); sorption (distribution coefficient); and degradation (first order decay). The input data required are: meteorological data, landuse/cover map with event mean concentration attributes, geological maps with hydraulic and geochemical attributes, and topographic and water table elevation data in grid form. Standard outputs include distributions of: surface runoff, infiltration, potential recharge, ground level slope, interflow, actual recharge, pollutant fluxes in surface runoff, travel times of each pollutant through the unsaturated zone, and the pollutant fluxes and concentrations at the water table. The process of validation has commenced with a study of the Triassic Sandstone aquifer underlying Birmingham, UK. UGIf predicts a similar average recharge rate for the aquifer as previous groundwater flow modelling studies, but with significantly more spatial detail: in particular the results indicate that recharge through paved areas may be more important than previously thought. The results also highlight the need for more knowledge/data on the following: runoff estimation; interflow (including the effects of lateral flow and channelling on flow times and therefore chemistry); evapotranspiration in paved areas; the nature of unsaturated zone flow below paved areas; and the role of the pipe network

  4. The Key to Acetate: Metabolic Fluxes of Acetic Acid Bacteria under Cocoa Pulp Fermentation-Simulating Conditions

    Science.gov (United States)

    Adler, Philipp; Frey, Lasse Jannis; Berger, Antje; Bolten, Christoph Josef; Hansen, Carl Erik

    2014-01-01

    Acetic acid bacteria (AAB) play an important role during cocoa fermentation, as their main product, acetate, is a major driver for the development of the desired cocoa flavors. Here, we investigated the specialized metabolism of these bacteria under cocoa pulp fermentation-simulating conditions. A carefully designed combination of parallel 13C isotope labeling experiments allowed the elucidation of intracellular fluxes in the complex environment of cocoa pulp, when lactate and ethanol were included as primary substrates among undefined ingredients. We demonstrate that AAB exhibit a functionally separated metabolism during coconsumption of two-carbon and three-carbon substrates. Acetate is almost exclusively derived from ethanol, while lactate serves for the formation of acetoin and biomass building blocks. Although this is suboptimal for cellular energetics, this allows maximized growth and conversion rates. The functional separation results from a lack of phosphoenolpyruvate carboxykinase and malic enzymes, typically present in bacteria to interconnect metabolism. In fact, gluconeogenesis is driven by pyruvate phosphate dikinase. Consequently, a balanced ratio of lactate and ethanol is important for the optimum performance of AAB. As lactate and ethanol are individually supplied by lactic acid bacteria and yeasts during the initial phase of cocoa fermentation, respectively, this underlines the importance of a well-balanced microbial consortium for a successful fermentation process. Indeed, AAB performed the best and produced the largest amounts of acetate in mixed culture experiments when lactic acid bacteria and yeasts were both present. PMID:24837393

  5. Radiopharmaceuticals for Assessment of Altered Metabolism and Biometal Fluxes in Brain Aging and Alzheimer's Disease with Positron Emission Tomography.

    Science.gov (United States)

    Xie, Fang; Peng, Fangyu

    2017-01-01

    Aging is a risk factor for Alzheimer's disease (AD). There are changes of brain metabolism and biometal fluxes due to brain aging, which may play a role in pathogenesis of AD. Positron emission tomography (PET) is a versatile tool for tracking alteration of metabolism and biometal fluxes due to brain aging and AD. Age-dependent changes in cerebral glucose metabolism can be tracked with PET using 2-deoxy-2-[18F]-fluoro-D-glucose (18F-FDG), a radiolabeled glucose analogue, as a radiotracer. Based on different patterns of altered cerebral glucose metabolism, 18F-FDG PET was clinically used for differential diagnosis of AD and Frontotemporal dementia (FTD). There are continued efforts to develop additional radiopharmaceuticals or radiotracers for assessment of age-dependent changes of various metabolic pathways and biometal fluxes due to brain aging and AD with PET. Elucidation of age-dependent changes of brain metabolism and altered biometal fluxes is not only significant for a better mechanistic understanding of brain aging and the pathophysiology of AD, but also significant for identification of new targets for the prevention, early diagnosis, and treatment of AD.

  6. Human taurine metabolism: fluxes and fractional extraction rates of the gut, liver, and kidneys

    NARCIS (Netherlands)

    van Stijn, Mireille F. M.; Vermeulen, Mechteld A. R.; Siroen, Michiel P. C.; Wong, Leanne N.; van den Tol, M. Petrousjka; Ligthart-Melis, Gerdien C.; Houdijk, Alexander P. J.; van Leeuwen, Paul A. M.

    2012-01-01

    Taurine is involved in numerous biological processes. However, taurine plasma level decreases in response to pathological conditions, suggesting an increased need. Knowledge on human taurine metabolism is scarce and only described by arterial-venous differences across a single organ. Here we present

  7. Transcriptional and metabolic flux profiling of triadimefon effects on cultured hepatocytes

    International Nuclear Information System (INIS)

    Iyer, Vidya V.; Ovacik, Meric A.; Androulakis, Ioannis P.; Roth, Charles M.; Ierapetritou, Marianthi G.

    2010-01-01

    Conazoles are a class of azole fungicides used to prevent fungal growth in agriculture, for treatment of fungal infections, and are found to be tumorigenic in rats and/or mice. In this study, cultured primary rat hepatocytes were treated to two different concentrations (0.3 and 0.15 mM) of triadimefon, which is a tumorigenic conazole in rat and mouse liver, on a temporal basis with daily media change. Following treatment, cells were harvested for microarray data ranging from 6 to 72 h. Supernatant was collected daily for three days, and the concentrations of various metabolites in the media and supernatant were quantified. Gene expression changes were most significant following exposure to 0.3 mM triadimefon and were characterized mainly by metabolic pathways related to carbohydrate, lipid and amino acid metabolism. Correspondingly, metabolic network flexibility analysis demonstrated a switch from fatty acid synthesis to fatty acid oxidation in cells exposed to triadimefon. It is likely that fatty acid oxidation is active in order to supply energy required for triadimefon detoxification. In 0.15 mM triadimefon treatment, the hepatocytes are able to detoxify the relatively low concentration of triadimefon with less pronounced changes in hepatic metabolism.

  8. Enzyme allocation problems in kinetic metabolic networks: Optimal solutions are elementary flux modes

    Czech Academy of Sciences Publication Activity Database

    Müller, Stefan; Regensburger, G.; Steuer, Ralf

    2014-01-01

    Roč. 347, APR 2014 (2014), s. 182-190 ISSN 0022-5193 R&D Projects: GA MŠk(CZ) EE2.3.20.0256 Institutional support: RVO:67179843 Keywords : metabolic optimization * enzyme kinetics * oriented matroid * elementary vector * conformal sum Subject RIV: EI - Biotechnology ; Bionics Impact factor: 2.116, year: 2014

  9. {sup 13}C dynamic nuclear polarization for measuring metabolic flux in endothelial progenitor cells

    Energy Technology Data Exchange (ETDEWEB)

    Nielsen, Nathalie; Laustsen, Christoffer; Bertelsen, Lotte Bonde, E-mail: Lotte@clin.au.dk

    2016-11-15

    Endothelial progenitor cells (EPCs) represent a heterogeneous cell population that is believed to be involved in vasculogenesis. With the purpose of enhancing endothelial repair, EPCs could have a potential for future cell therapies. Due to the low amount of EPCs in the peripheral circulating blood, in vitro expansion is needed before administration to recipients and the effects of in vitro culturing is still an under-evaluated field with little knowledge of how the cells change over time in culture. The aim of this study was to use hyperpolarised carbon-13 magnetic resonance spectroscopy to profile important metabolic pathways in a population of progenitor cells and to show that cell culturing in 3D scaffolds seem to block the metabolic processes that leads to cell senescence. The metabolic breakdown of hyperpolarized [1-{sup 13}C]pyruvate was followed after injection of the substrate to a bioreactor system with EPCs either adhered to 3D printed scaffolds or kept in cell suspension. The pyruvate-to-lactate conversion was elevated in suspension of EPCs compared to the EPCs adhered to scaffolds. Furthermore in the setup with EPCs in suspension, an increase in lactate production was seen over time indicating that the older the cultures of EPCs was before using the cells for cell suspension experiments, the more lactate they produce, compared to a constant lactate level in the cells adhered to scaffolds. It could therefore be stated that cells grown first in 2D culture and subsequent prepared for cell suspension show a metabolism with higher lactate production consistent with cells senescence processes compared to cells grown first at 2D culture and subsequent in the 3D printed scaffolds, where metabolism shows no sign of metabolic shifting during the monitored period. - Highlights: • Hyperpolarized 13C MRS detects EPCs metabolic changes associated with ageing and cultivating conditions. • Increased lactate production in EPC’s correlates positively with aging.

  10. A systems biology framework for modeling metabolic enzyme inhibition of Mycobacterium tuberculosis

    Directory of Open Access Journals (Sweden)

    Reifman Jaques

    2009-09-01

    Full Text Available Abstract Background Because metabolism is fundamental in sustaining microbial life, drugs that target pathogen-specific metabolic enzymes and pathways can be very effective. In particular, the metabolic challenges faced by intracellular pathogens, such as Mycobacterium tuberculosis, residing in the infected host provide novel opportunities for therapeutic intervention. Results We developed a mathematical framework to simulate the effects on the growth of a pathogen when enzymes in its metabolic pathways are inhibited. Combining detailed models of enzyme kinetics, a complete metabolic network description as modeled by flux balance analysis, and a dynamic cell population growth model, we quantitatively modeled and predicted the dose-response of the 3-nitropropionate inhibitor on the growth of M. tuberculosis in a medium whose carbon source was restricted to fatty acids, and that of the 5'-O-(N-salicylsulfamoyl adenosine inhibitor in a medium with low-iron concentration. Conclusion The predicted results quantitatively reproduced the experimentally measured dose-response curves, ranging over three orders of magnitude in inhibitor concentration. Thus, by allowing for detailed specifications of the underlying enzymatic kinetics, metabolic reactions/constraints, and growth media, our model captured the essential chemical and biological factors that determine the effects of drug inhibition on in vitro growth of M. tuberculosis cells.

  11. Ozone Flux Measurement and Modelling on Leaf/Shoot and Canopy Scale

    Directory of Open Access Journals (Sweden)

    Ludger Grünhage

    Full Text Available The quantitative study of the ozone effects on agricultural and forest vegetation requires the knowledge of the pollutant dose absorbed by plants via leaf stomata, i.e. the stomatal flux. Nevertheless, the toxicologically effective dose can differ from the stomatal flux because a pool of scavenging and detoxification processes reduce the amount of pollutant responsible of the expression of the harmful effects. The measurement of the stomatal flux is not immediate and the quantification of the effective dose is still troublesome. The paper examines the conceptual aspects of ozone flux measurement and modelling in agricultural and ecological research. The ozone flux paradigm is conceptualized into a toxicological frame and faced at two different scales: leaf/shoot and canopy scales. Leaf and shoot scale flux measurements require gas-exchange enclosure techniques, while canopy scale flux measurements need a micrometeorological approach including techniques such as eddy covariance and the aerodynamical gradient. At both scales, not all the measured ozone flux is stomatal flux. In fact, a not negligible amount of ozone is destroyed on external plant surfaces, like leaf cuticles, or by gas phase reaction with biogenic volatile compounds. The stomatal portion of flux can be calculated from concurrent measurements of water vapour fluxes at both scales. Canopy level flux measurements require very fast sensors and the fulfilment of many conditions to ensure that the measurements made above the canopy really reflect the canopy fluxes (constant flux hypothesis. Again, adjustments are necessary in order to correct for air density fluctuations and sensor-surface alignment break. As far as regards flux modelling, at leaf level the stomatal flux is simply obtained by multiplying the ozone concentration on the leaf with the stomatal conductance predicted by means of physiological models fed by meteorological parameter. At canopy level the stomatal flux is

  12. Kinetic modeling of cell metabolism for microbial production.

    Science.gov (United States)

    Costa, Rafael S; Hartmann, Andras; Vinga, Susana

    2016-02-10

    Kinetic models of cellular metabolism are important tools for the rational design of metabolic engineering strategies and to explain properties of complex biological systems. The recent developments in high-throughput experimental data are leading to new computational approaches for building kinetic models of metabolism. Herein, we briefly survey the available databases, standards and software tools that can be applied for kinetic models of metabolism. In addition, we give an overview about recently developed ordinary differential equations (ODE)-based kinetic models of metabolism and some of the main applications of such models are illustrated in guiding metabolic engineering design. Finally, we review the kinetic modeling approaches of large-scale networks that are emerging, discussing their main advantages, challenges and limitations. Copyright © 2015 Elsevier B.V. All rights reserved.

  13. Calibration of a distributed hydrology and land surface model using energy flux measurements

    DEFF Research Database (Denmark)

    Larsen, Morten Andreas Dahl; Refsgaard, Jens Christian; Jensen, Karsten H.

    2016-01-01

    In this study we develop and test a calibration approach on a spatially distributed groundwater-surface water catchment model (MIKE SHE) coupled to a land surface model component with particular focus on the water and energy fluxes. The model is calibrated against time series of eddy flux measure...

  14. Hybrid elementary flux analysis/nonparametric modeling: application for bioprocess control

    Directory of Open Access Journals (Sweden)

    Alves Paula M

    2007-01-01

    Full Text Available Abstract Background The progress in the "-omic" sciences has allowed a deeper knowledge on many biological systems with industrial interest. This knowledge is still rarely used for advanced bioprocess monitoring and control at the bioreactor level. In this work, a bioprocess control method is presented, which is designed on the basis of the metabolic network of the organism under consideration. The bioprocess dynamics are formulated using hybrid rigorous/data driven systems and its inherent structure is defined by the metabolism elementary modes. Results The metabolic network of the system under study is decomposed into elementary modes (EMs, which are the simplest paths able to operate coherently in steady-state. A reduced reaction mechanism in the form of simplified reactions connecting substrates with end-products is obtained. A dynamical hybrid system integrating material balance equations, EMs reactions stoichiometry and kinetics was formulated. EMs kinetics were defined as the product of two terms: a mechanistic/empirical known term and an unknown term that must be identified from data, in a process optimisation perspective. This approach allows the quantification of fluxes carried by individual elementary modes which is of great help to identify dominant pathways as a function of environmental conditions. The methodology was employed to analyse experimental data of recombinant Baby Hamster Kidney (BHK-21A cultures producing a recombinant fusion glycoprotein. The identified EMs kinetics demonstrated typical glucose and glutamine metabolic responses during cell growth and IgG1-IL2 synthesis. Finally, an online optimisation study was conducted in which the optimal feeding strategies of glucose and glutamine were calculated after re-estimation of model parameters at each sampling time. An improvement in the final product concentration was obtained as a result of this online optimisation. Conclusion The main contribution of this work is a

  15. Validation of transport models using additive flux minimization technique

    Energy Technology Data Exchange (ETDEWEB)

    Pankin, A. Y.; Kruger, S. E. [Tech-X Corporation, 5621 Arapahoe Ave., Boulder, Colorado 80303 (United States); Groebner, R. J. [General Atomics, San Diego, California 92121 (United States); Hakim, A. [Princeton Plasma Physics Laboratory, Princeton, New Jersey 08543-0451 (United States); Kritz, A. H.; Rafiq, T. [Department of Physics, Lehigh University, Bethlehem, Pennsylvania 18015 (United States)

    2013-10-15

    A new additive flux minimization technique is proposed for carrying out the verification and validation (V and V) of anomalous transport models. In this approach, the plasma profiles are computed in time dependent predictive simulations in which an additional effective diffusivity is varied. The goal is to obtain an optimal match between the computed and experimental profile. This new technique has several advantages over traditional V and V methods for transport models in tokamaks and takes advantage of uncertainty quantification methods developed by the applied math community. As a demonstration of its efficiency, the technique is applied to the hypothesis that the paleoclassical density transport dominates in the plasma edge region in DIII-D tokamak discharges. A simplified version of the paleoclassical model that utilizes the Spitzer resistivity for the parallel neoclassical resistivity and neglects the trapped particle effects is tested in this paper. It is shown that a contribution to density transport, in addition to the paleoclassical density transport, is needed in order to describe the experimental profiles. It is found that more additional diffusivity is needed at the top of the H-mode pedestal, and almost no additional diffusivity is needed at the pedestal bottom. The implementation of this V and V technique uses the FACETS::Core transport solver and the DAKOTA toolkit for design optimization and uncertainty quantification. The FACETS::Core solver is used for advancing the plasma density profiles. The DAKOTA toolkit is used for the optimization of plasma profiles and the computation of the additional diffusivity that is required for the predicted density profile to match the experimental profile.

  16. Validation of transport models using additive flux minimization technique

    International Nuclear Information System (INIS)

    Pankin, A. Y.; Kruger, S. E.; Groebner, R. J.; Hakim, A.; Kritz, A. H.; Rafiq, T.

    2013-01-01

    A new additive flux minimization technique is proposed for carrying out the verification and validation (V and V) of anomalous transport models. In this approach, the plasma profiles are computed in time dependent predictive simulations in which an additional effective diffusivity is varied. The goal is to obtain an optimal match between the computed and experimental profile. This new technique has several advantages over traditional V and V methods for transport models in tokamaks and takes advantage of uncertainty quantification methods developed by the applied math community. As a demonstration of its efficiency, the technique is applied to the hypothesis that the paleoclassical density transport dominates in the plasma edge region in DIII-D tokamak discharges. A simplified version of the paleoclassical model that utilizes the Spitzer resistivity for the parallel neoclassical resistivity and neglects the trapped particle effects is tested in this paper. It is shown that a contribution to density transport, in addition to the paleoclassical density transport, is needed in order to describe the experimental profiles. It is found that more additional diffusivity is needed at the top of the H-mode pedestal, and almost no additional diffusivity is needed at the pedestal bottom. The implementation of this V and V technique uses the FACETS::Core transport solver and the DAKOTA toolkit for design optimization and uncertainty quantification. The FACETS::Core solver is used for advancing the plasma density profiles. The DAKOTA toolkit is used for the optimization of plasma profiles and the computation of the additional diffusivity that is required for the predicted density profile to match the experimental profile

  17. MODELS OF NEPTUNE-MASS EXOPLANETS: EMERGENT FLUXES AND ALBEDOS

    International Nuclear Information System (INIS)

    Spiegel, David S.; Burrows, Adam; Ibgui, Laurent; Hubeny, Ivan; Milsom, John A.

    2010-01-01

    There are now many known exoplanets with Msin i within a factor of 2 of Neptune's, including the transiting planets GJ 436b and HAT-P-11b. Planets in this mass range are different from their more massive cousins in several ways that are relevant to their radiative properties and thermal structures. By analogy with Neptune and Uranus, they are likely to have metal abundances that are an order of magnitude or more greater than those of larger, more massive planets. This increases their opacity, decreases Rayleigh scattering, and changes their equation of state. Furthermore, their smaller radii mean that fluxes from these planets are roughly an order of magnitude lower than those of otherwise identical gas giant planets. Here, we compute a range of plausible radiative equilibrium models of GJ 436b and HAT-P-11b. In addition, we explore the dependence of generic Neptune-mass planets on a range of physical properties, including their distance from their host stars, their metallicity, the spectral type of their stars, the redistribution of heat in their atmospheres, and the possible presence of additional optical opacity in their upper atmospheres.

  18. In vivo 13C MRS in the mouse brain at 14.1 Tesla and metabolic flux quantification under infusion of [1,6-13C2]glucose.

    Science.gov (United States)

    Lai, Marta; Lanz, Bernard; Poitry-Yamate, Carole; Romero, Jackeline F; Berset, Corina M; Cudalbu, Cristina; Gruetter, Rolf

    2017-01-01

    In vivo 13 C magnetic resonance spectroscopy (MRS) enables the investigation of cerebral metabolic compartmentation while, e.g. infusing 13 C-labeled glucose. Metabolic flux analysis of 13 C turnover previously yielded quantitative information of glutamate and glutamine metabolism in humans and rats, while the application to in vivo mouse brain remains exceedingly challenging. In the present study, 13 C direct detection at 14.1 T provided highly resolved in vivo spectra of the mouse brain while infusing [1,6- 13 C 2 ]glucose for up to 5 h. 13 C incorporation to glutamate and glutamine C4, C3, and C2 and aspartate C3 were detected dynamically and fitted to a two-compartment model: flux estimation of neuron-glial metabolism included tricarboxylic acid cycle (TCA) flux in astrocytes (V g  = 0.16 ± 0.03 µmol/g/min) and neurons (V TCA n  = 0.56 ± 0.03 µmol/g/min), pyruvate carboxylase activity (V PC  = 0.041 ± 0.003 µmol/g/min) and neurotransmission rate (V NT  = 0.084 ± 0.008 µmol/g/min), resulting in a cerebral metabolic rate of glucose (CMR glc ) of 0.38 ± 0.02 µmol/g/min, in excellent agreement with that determined with concomitant 18 F-fluorodeoxyglucose positron emission tomography ( 18 FDG PET).We conclude that modeling of neuron-glial metabolism in vivo is accessible in the mouse brain from 13 C direct detection with an unprecedented spatial resolution under [1,6- 13 C 2 ]glucose infusion.

  19. Systematic construction of kinetic models from genome-scale metabolic networks.

    Directory of Open Access Journals (Sweden)

    Natalie J Stanford

    Full Text Available The quantitative effects of environmental and genetic perturbations on metabolism can be studied in silico using kinetic models. We present a strategy for large-scale model construction based on a logical layering of data such as reaction fluxes, metabolite concentrations, and kinetic constants. The resulting models contain realistic standard rate laws and plausible parameters, adhere to the laws of thermodynamics, and reproduce a predefined steady state. These features have not been simultaneously achieved by previous workflows. We demonstrate the advantages and limitations of the workflow by translating the yeast consensus metabolic network into a kinetic model. Despite crudely selected data, the model shows realistic control behaviour, a stable dynamic, and realistic response to perturbations in extracellular glucose concentrations. The paper concludes by outlining how new data can continuously be fed into the workflow and how iterative model building can assist in directing experiments.

  20. Systematic Construction of Kinetic Models from Genome-Scale Metabolic Networks

    Science.gov (United States)

    Smallbone, Kieran; Klipp, Edda; Mendes, Pedro; Liebermeister, Wolfram

    2013-01-01

    The quantitative effects of environmental and genetic perturbations on metabolism can be studied in silico using kinetic models. We present a strategy for large-scale model construction based on a logical layering of data such as reaction fluxes, metabolite concentrations, and kinetic constants. The resulting models contain realistic standard rate laws and plausible parameters, adhere to the laws of thermodynamics, and reproduce a predefined steady state. These features have not been simultaneously achieved by previous workflows. We demonstrate the advantages and limitations of the workflow by translating the yeast consensus metabolic network into a kinetic model. Despite crudely selected data, the model shows realistic control behaviour, a stable dynamic, and realistic response to perturbations in extracellular glucose concentrations. The paper concludes by outlining how new data can continuously be fed into the workflow and how iterative model building can assist in directing experiments. PMID:24324546

  1. Integrative Analysis of Metabolic Models – from Structure to Dynamics

    Energy Technology Data Exchange (ETDEWEB)

    Hartmann, Anja, E-mail: hartmann@ipk-gatersleben.de [Leibniz Institute of Plant Genetics and Crop Plant Research (IPK), Gatersleben (Germany); Schreiber, Falk [Monash University, Melbourne, VIC (Australia); Martin-Luther-University Halle-Wittenberg, Halle (Germany)

    2015-01-26

    The characterization of biological systems with respect to their behavior and functionality based on versatile biochemical interactions is a major challenge. To understand these complex mechanisms at systems level modeling approaches are investigated. Different modeling formalisms allow metabolic models to be analyzed depending on the question to be solved, the biochemical knowledge and the availability of experimental data. Here, we describe a method for an integrative analysis of the structure and dynamics represented by qualitative and quantitative metabolic models. Using various formalisms, the metabolic model is analyzed from different perspectives. Determined structural and dynamic properties are visualized in the context of the metabolic model. Interaction techniques allow the exploration and visual analysis thereby leading to a broader understanding of the behavior and functionality of the underlying biological system. The System Biology Metabolic Model Framework (SBM{sup 2} – Framework) implements the developed method and, as an example, is applied for the integrative analysis of the crop plant potato.

  2. On the analytical flux distribution modeling of an axial-flux surface-mounted permanent magnet motor for control applications

    International Nuclear Information System (INIS)

    Liu, C.-T.; Lin, S.-C.; Chiang, T.-S.

    2004-01-01

    By combining the recoil line characteristics of permanent magnet and the equivalent operational magnetic circuits at various rotor positions, a systematic procedure for developing the desired analytical model of an axial-flux surface-mounted permanent magnet motor can be devised. Supported by detailed three-dimensional finite element analysis results and statistical evaluations, accuracies of the developed analytical model can be guaranteed. With such well developed system model, the relative high-precision controls and operations of the motor can then be conveniently realized

  3. An algebraic stress/flux model for two-phase turbulent flow

    International Nuclear Information System (INIS)

    Kumar, R.

    1995-12-01

    An algebraic stress model (ASM) for turbulent Reynolds stress and a flux model for turbulent heat flux are proposed for two-phase bubbly and slug flows. These mathematical models are derived from the two-phase transport equations for Reynolds stress and turbulent heat flux, and provide C μ , a turbulent constant which defines the level of eddy viscosity, as a function of the interfacial terms. These models also include the effect of heat transfer. When the interfacial drag terms and the interfacial momentum transfer terms are absent, the model reduces to a single-phase model used in the literature

  4. Multi-year Estimates of Methane Fluxes in Alaska from an Atmospheric Inverse Model

    Science.gov (United States)

    Miller, S. M.; Commane, R.; Chang, R. Y. W.; Miller, C. E.; Michalak, A. M.; Dinardo, S. J.; Dlugokencky, E. J.; Hartery, S.; Karion, A.; Lindaas, J.; Sweeney, C.; Wofsy, S. C.

    2015-12-01

    We estimate methane fluxes across Alaska over a multi-year period using observations from a three-year aircraft campaign, the Carbon Arctic Reservoirs Vulnerability Experiment (CARVE). Existing estimates of methane from Alaska and other Arctic regions disagree in both magnitude and distribution, and before the CARVE campaign, atmospheric observations in the region were sparse. We combine these observations with an atmospheric particle trajectory model and a geostatistical inversion to estimate surface fluxes at the model grid scale. We first use this framework to estimate the spatial distribution of methane fluxes across the state. We find the largest fluxes in the south-east and North Slope regions of Alaska. This distribution is consistent with several estimates of wetland extent but contrasts with the distribution in most existing flux models. These flux models concentrate methane in warmer or more southerly regions of Alaska compared to the estimate presented here. This result suggests a discrepancy in how existing bottom-up models translate wetland area into methane fluxes across the state. We next use the inversion framework to explore inter-annual variability in regional-scale methane fluxes for 2012-2014. We examine the extent to which this variability correlates with weather or other environmental conditions. These results indicate the possible sensitivity of wetland fluxes to near-term variability in climate.

  5. Seasonality of Overstory and Understory Fluxes in a Semi-Arid Oak Savanna: What can be Learned from Comparing Measured and Modeled Fluxes?

    Science.gov (United States)

    Raz-Yaseef, N.; Sonnentag, O.; Kobayashi, H.; Chen, J. M.; Verfaillie, J. G.; Ma, S.; Baldocchi, D. D.

    2011-12-01

    Semi-arid climates experience large seasonal and inter-annual variability in radiation and precipitation, creating natural conditions adequate to study how year-to-year changes affect atmosphere-biosphere fluxes. Especially, savanna ecosystems, that combine tree and below-canopy components, create a unique environment in which phenology dramatically changes between seasons. We used a 10-year flux database in order to define seasonal and interannual variability of climatic inputs and fluxes, and evaluate model capability to reproduce observed variability. This is based on the perception that model capability to construct the deviation, and not the average, is important in order to correctly predict ecosystem sensitivity to climate change. Our research site is a low density and low LAI (0.8) semi-arid savanna, located at Tonzi Ranch, Northern California. In this system, trees are active during the warm season (Mar - Oct), and grasses are active during the wet season (Dec - May). Measurements of carbon and water fluxes above and below the tree canopy using eddy covariance and supplementary measurements have been made since 2001. Fluxes were simulated using bio-meteorological process-oriented ecosystem models: BEPS and 3D-CAONAK. Models were partly capable of reproducing fluxes on daily scales (R2=0.66). We then compared model outputs for different ecosystem components and seasons, and found distinct seasons with high correlations while other seasons were purely represented. Comparison was much higher for ET than for GPP. The understory was better simulated than the overstory. CANOAK overestimated spring understory fluxes, probably due to the capability to directly calculated 3D radiative transfer. BEPS underestimated spring understory fluxes, following the pre-description of grass die-off. Both models underestimated peak spring overstory fluxes. During winter tree dormant, modeled fluxes were null, but occasional high fluxes of both ET and GPP were measured following

  6. Improving Bioenergy Crops through Dynamic Metabolic Modeling

    Directory of Open Access Journals (Sweden)

    Mojdeh Faraji

    2017-10-01

    Full Text Available Enormous advances in genetics and metabolic engineering have made it possible, in principle, to create new plants and crops with improved yield through targeted molecular alterations. However, while the potential is beyond doubt, the actual implementation of envisioned new strains is often difficult, due to the diverse and complex nature of plants. Indeed, the intrinsic complexity of plants makes intuitive predictions difficult and often unreliable. The hope for overcoming this challenge is that methods of data mining and computational systems biology may become powerful enough that they could serve as beneficial tools for guiding future experimentation. In the first part of this article, we review the complexities of plants, as well as some of the mathematical and computational methods that have been used in the recent past to deepen our understanding of crops and their potential yield improvements. In the second part, we present a specific case study that indicates how robust models may be employed for crop improvements. This case study focuses on the biosynthesis of lignin in switchgrass (Panicum virgatum. Switchgrass is considered one of the most promising candidates for the second generation of bioenergy production, which does not use edible plant parts. Lignin is important in this context, because it impedes the use of cellulose in such inedible plant materials. The dynamic model offers a platform for investigating the pathway behavior in transgenic lines. In particular, it allows predictions of lignin content and composition in numerous genetic perturbation scenarios.

  7. Flux response of glycolysis and storage metabolism during rapid feast/famine conditions in Penicillium chrysogenum using dynamic (13)C labeling.

    Science.gov (United States)

    de Jonge, Lodewijk; Buijs, Nicolaas A A; Heijnen, Joseph J; van Gulik, Walter M; Abate, Alessandro; Wahl, S Aljoscha

    2014-03-01

    The scale-up of fermentation processes frequently leads to a reduced productivity compared to small-scale screening experiments. Large-scale mixing limitations that lead to gradients in substrate and oxygen availability could influence the microorganism performance. Here, the impact of substrate gradients on a penicillin G producing Penicillium chrysogenum cultivation was analyzed using an intermittent glucose feeding regime. The intermittent feeding led to fluctuations in the extracellular glucose concentration between 400 μM down to 6.5 μM at the end of the cycle. The intracellular metabolite concentrations responded strongly and showed up to 100-fold changes. The intracellular flux changes were estimated on the basis of dynamic (13) C mass isotopomer measurements during three cycles of feast and famine using a novel hybrid modeling approach. The flux estimations indicated a high turnover of internal and external storage metabolites in P. chrysogenum under feast/famine conditions. The synthesis and degradation of storage requires cellular energy (ATP and UTP) in competition with other cellular functions including product formation. Especially, 38% of the incoming glucose was recycled once in storage metabolism. This result indicated that storage turnover is increased under dynamic cultivation conditions and contributes to the observed decrease in productivity compared to reference steady-state conditions. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  8. Oxygen-enriched fermentation of sodium gluconate by Aspergillus niger and its impact on intracellular metabolic flux distributions.

    Science.gov (United States)

    Shen, Yuting; Tian, Xiwei; Zhao, Wei; Hang, Haifeng; Chu, Ju

    2018-01-01

    Different concentrations of oxygen-enriched air were utilized for sodium gluconate (SG) fermentation by Aspergillus niger. The fermentation time shortened from 20 to 15.5 h due to the increase of volumetric oxygen transfer coefficient (K L a) and the formation of more dispersed mycelia when inlet oxygen concentration ascended from 21 to 32%. According to metabolic flux analysis, during the growth phase, extracellular glucose for SG synthesis accounted for 79.0 and 85.3% with air and oxygen-enriched air (25%), respectively, whereas the proportions were 89.4 and 93.0% in the stationary phase. Intracellular glucose consumption decreased in oxygen-enriched fermentation, as cell respiration was more high-efficiently performed. Metabolic profiling indicated that most intermediates in TCA cycle and EMP pathway had smaller pool sizes in oxygen-enriched fermentations. Moreover, the main by-product of citric acid dramatically decreased from 1.36 to 0.34 g L -1 in oxygen-enriched fermentation. And the sodium gluconate yield increased from 0.856 to 0.903 mol mol -1 .

  9. Fructan biosynthesis and degradation as part of plant metabolism controlling sugar fluxes during durum wheat kernel maturation

    Directory of Open Access Journals (Sweden)

    Sara eCimini

    2015-02-01

    Full Text Available Wheat kernels contain fructans, fructose based oligosaccharides with prebiotic properties, in levels between 2 and 35 weight % depending on the developmental stage of the kernel. To improve knowledge on the metabolic pathways leading to fructan storage and degradation, carbohydrate fluxes occurring during durum wheat kernel development were analyzed. Kernels were collected at various developmental stages and quali-quantitative analysis of carbohydrates (mono- and di-saccharides, fructans, starch was performed, alongside analysis of the activities and gene expression of the enzymes involved in their biosynthesis and hydrolysis. High resolution HPAEC-PAD of fructan contained in durum wheat kernels revealed that fructan content is higher at the beginning of kernel development, when fructans with higher DP, such as bifurcose and 1,1-nystose, were mainly found. The changes in fructan pool observed during kernel maturation might be part of the signaling pathways influencing carbohydrate metabolism and storage in wheat kernels during development. During the first developmental stages fructan accumulation may contribute to make kernels more effective Suc sinks and to participate in osmotic regulation while the observed decrease in their content may mark the transition to later developmental stages, transition that is also orchestrated by changes in redox balance.

  10. Reliable and efficient solution of genome-scale models of Metabolism and macromolecular Expression

    DEFF Research Database (Denmark)

    Ma, Ding; Yang, Laurence; Fleming, Ronan M. T.

    2017-01-01

    orders of magnitude. Data values also have greatly varying magnitudes. Standard double-precision solvers may return inaccurate solutions or report that no solution exists. Exact simplex solvers based on rational arithmetic require a near-optimal warm start to be practical on large problems (current ME......Constraint-Based Reconstruction and Analysis (COBRA) is currently the only methodology that permits integrated modeling of Metabolism and macromolecular Expression (ME) at genome-scale. Linear optimization computes steady-state flux solutions to ME models, but flux values are spread over many...... models have 70,000 constraints and variables and will grow larger). We have developed a quadrupleprecision version of our linear and nonlinear optimizer MINOS, and a solution procedure (DQQ) involving Double and Quad MINOS that achieves reliability and efficiency for ME models and other challenging...

  11. Parameterization of a ruminant model of phosphorus digestion and metabolism.

    Science.gov (United States)

    Feng, X; Knowlton, K F; Hanigan, M D

    2015-10-01

    The objective of the current work was to parameterize the digestive elements of the model of Hill et al. (2008) using data collected from animals that were ruminally, duodenally, and ileally cannulated, thereby providing a better understanding of the digestion and metabolism of P fractions in growing and lactating cattle. The model of Hill et al. (2008) was fitted and evaluated for adequacy using the data from 6 animal studies. We hypothesized that sufficient data would be available to estimate P digestion and metabolism parameters and that these parameters would be sufficient to derive P bioavailabilities of a range of feed ingredients. Inputs to the model were dry matter intake; total feed P concentration (fPtFd); phytate (Pp), organic (Po), and inorganic (Pi) P as fractions of total P (fPpPt, fPoPt, fPiPt); microbial growth; amount of Pi and Pp infused into the omasum or ileum; milk yield; and BW. The available data were sufficient to derive all model parameters of interest. The final model predicted that given 75 g/d of total P input, the total-tract digestibility of P was 40.8%, Pp digestibility in the rumen was 92.4%, and in the total-tract was 94.7%. Blood P recycling to the rumen was a major source of Pi flow into the small intestine, and the primary route of excretion. A large proportion of Pi flowing to the small intestine was absorbed; however, additional Pi was absorbed from the large intestine (3.15%). Absorption of Pi from the small intestine was regulated, and given the large flux of salivary P recycling, the effective fractional small intestine absorption of available P derived from the diet was 41.6% at requirements. Milk synthesis used 16% of total absorbed P, and less than 1% was excreted in urine. The resulting model could be used to derive P bioavailabilities of commonly used feedstuffs in cattle production. Copyright © 2015 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

  12. Cerebral Metabolic Changes Related to Oxidative Metabolism in a Model of Bacterial Meningitis Induced by Lipopolysaccharide

    DEFF Research Database (Denmark)

    Munk, Michael; Rom Poulsen, Frantz; Larsen, Lykke

    2018-01-01

    BACKGROUND: Cerebral mitochondrial dysfunction is prominent in the pathophysiology of severe bacterial meningitis. In the present study, we hypothesize that the metabolic changes seen after intracisternal lipopolysaccharide (LPS) injection in a piglet model of meningitis is compatible...... with mitochondrial dysfunction and resembles the metabolic patterns seen in patients with bacterial meningitis. METHODS: Eight pigs received LPS injection in cisterna magna, and four pigs received NaCl in cisterna magna as a control. Biochemical variables related to energy metabolism were monitored by intracerebral...... dysfunction with increasing cerebral LPR due to increased lactate and normal pyruvate, PbtO2, and ICP. The metabolic pattern resembles the one observed in patients with bacterial meningitis. Metabolic monitoring in these patients is feasible to monitor for cerebral metabolic derangements otherwise missed...

  13. Testing a new flux rope model using the HELCATS CME catalogue

    Science.gov (United States)

    Rouillard, Alexis Paul; Lavarra, Michael

    2017-04-01

    We present a magnetically-driven flux rope model that computes the forces acting on a twisted magnetic flux rope from the Sun to 1AU. This model assumes a more realistic flux rope geometry than assumed before by these types of models. The balance of force is computed in an analogous manner to the well-known Chen flux-rope model. The 3-D vector components of the magnetic field measured by a probe flying through the flux rope can be extracted for any flux rope orientation imposed near the Sun. We test this model through a parametric study and a systematic comparison of the model with the HELCATS catalogues (imagery and in situ). We also report on our investigations of other physical mechanisms such as the shift of flux-surfaces associated with the magnetic forces acting to accelerate the flux rope from the lower to upper corona. Finally, we present an evaluation of this model for space-weather predictions. This work was partly funded by the HELCATS project under the FP7 EU contract number 606692.

  14. Bioenergy Ecosystem Land-Use Modelling and Field Flux Trial

    Science.gov (United States)

    McNamara, Niall; Bottoms, Emily; Donnison, Iain; Dondini, Marta; Farrar, Kerrie; Finch, Jon; Harris, Zoe; Ineson, Phil; Keane, Ben; Massey, Alice; McCalmont, Jon; Morison, James; Perks, Mike; Pogson, Mark; Rowe, Rebecca; Smith, Pete; Sohi, Saran; Tallis, Mat; Taylor, Gail; Yamulki, Sirwan

    2013-04-01

    loss after land use change at 100 fieldsites which encapsulate a range of UK climates and soil types. Our overall objective is to use our measured data to parameterise and validate the models that we will use to predict the implications of bioenergy crop deployment in the UK up to 2050. The resultant output will be a meta-model which will help facilitate decision making on the sustainable development of bioenergy in the UK, with potential deployment in other temperate climates around the world. Here we report on the outcome of the first of three years of work. This work is based on the Ecosystem Land Use Modelling & Soil Carbon GHG Flux Trial (ELUM) project, which was commissioned and funded by the Energy Technologies Institute (ETI). Don et al. (2012) Land-use change to bioenergy production in Europe: implications for the greenhouse gas balance and soil carbon. GCB Bioenergy 4, 372-379.

  15. Global constraints on Z2 fluxes in two different anisotropic limits of a hypernonagon Kitaev model

    Science.gov (United States)

    Kato, Yasuyuki; Kamiya, Yoshitomo; Nasu, Joji; Motome, Yukitoshi

    2018-05-01

    The Kitaev model is an exactly-soluble quantum spin model, whose ground state provides a canonical example of a quantum spin liquid. Spin excitations from the ground state are fractionalized into emergent matter fermions and Z2 fluxes. The Z2 flux excitation is pointlike in two dimensions, while it comprises a closed loop in three dimensions because of the local constraint for each closed volume. In addition, the fluxes obey global constraints involving (semi)macroscopic number of fluxes. We here investigate such global constraints in the Kitaev model on a three-dimensional lattice composed of nine-site elementary loops, dubbed the hypernonagon lattice, whose ground state is a chiral spin liquid. We consider two different anisotropic limits of the hypernonagon Kitaev model where the low-energy effective models are described solely by the Z2 fluxes. We show that there are two kinds of global constraints in the model defined on a three-dimensional torus, namely, surface and volume constraints: the surface constraint is imposed on the even-odd parity of the total number of fluxes threading a two-dimensional slice of the system, while the volume constraint is for the even-odd parity of the number of the fluxes through specific plaquettes whose total number is proportional to the system volume. In the two anisotropic limits, therefore, the elementary excitation of Z2 fluxes occurs in a pair of closed loops so as to satisfy both two global constraints as well as the local constraints.

  16. Idealised modelling of ocean circulation driven by conductive and hydrothermal fluxes at the seabed

    Science.gov (United States)

    Barnes, Jowan M.; Morales Maqueda, Miguel A.; Polton, Jeff A.; Megann, Alex P.

    2018-02-01

    Geothermal heating is increasingly recognised as an important factor affecting ocean circulation, with modelling studies suggesting that this heat source could lead to first-order changes in the formation rate of Antarctic Bottom Water, as well as a significant warming effect in the abyssal ocean. Where it has been represented in numerical models, however, the geothermal heat flux into the ocean is generally treated as an entirely conductive flux, despite an estimated one third of the global geothermal flux being introduced to the ocean via hydrothermal sources. A modelling study is presented which investigates the sensitivity of the geothermally forced circulation to the way heat is supplied to the abyssal ocean. An analytical two-dimensional model of the circulation is described, which demonstrates the effects of a volume flux through the ocean bed. A simulation using the NEMO numerical general circulation model in an idealised domain is then used to partition a heat flux between conductive and hydrothermal sources and explicitly test the sensitivity of the circulation to the formulation of the abyssal heat flux. Our simulations suggest that representing the hydrothermal flux as a mass exchange indeed changes the heat distribution in the abyssal ocean, increasing the advective heat transport from the abyss by up to 35% compared to conductive heat sources. Consequently, we suggest that the inclusion of hydrothermal fluxes can be an important addition to course-resolution ocean models.

  17. Metabolic flux distributions in Corynebacterium glutamicum during growth and lysine overproduction. Reprinted from Biotechnology and Bioengineering, Vol. 41, Pp 633-646 (1993).

    Science.gov (United States)

    Vallino, J J; Stephanopoulos, G

    2000-03-20

    The two main contributions of this article are the solidification of Corynebacterium glutamicum biochemistry guided by bioreaction network analysis, and the determination of basal metabolic flux distributions during growth and lysine synthesis. Employed methodology makes use of stoichiometrically based mass balances to determine flux distributions in the C. glutamicum metabolic network. Presented are a brief description of the methodology, a thorough literature review of glutamic acid bacteria biochemistry, and specific results obtained through a combination of fermentation studies and analysis-directed intracellular assays. The latter include the findings of the lack of activity of glyoxylate shunt, and that phosphoenolpyruvate carboxylase (PPC) is the only anaplerotic reaction expressed in C. glutamicum cultivated on glucose minimal media. Network simplifications afforded by the above findings facilitated the determination of metabolic flux distributions under a variety of culture conditions and led to the following conclusions. Both the pentose phosphate pathway and PPC support significant fluxes during growth and lysine overproduction, and that flux partitioning at the glucosa-6-phosphate branch point does not appear to limit lysine synthesis. Copyright 1993 John Wiley & Sons, Inc.

  18. Rational Design of a Corynebacterium glutamicum Pantothenate Production Strain and Ins Characterization by Metabolic Flux Analysis and Genome-Wide Transcriptional Profiling

    Czech Academy of Sciences Publication Activity Database

    Hüser, A.T.; Chassagnole, Ch.; Lindley, N.D.; Merkamm, M.; Guyonvarch, A.; Elišáková, Veronika; Pátek, Miroslav; Kalinowski, J.; Brune, I.; Pühler, A.; Tauch, A.

    2005-01-01

    Roč. 71, č. 6 (2005), s. 3255-3268 ISSN 0099-2240 Institutional research plan: CEZ:AV0Z50200510 Keywords : corynebacterium glutamicum * metabolic flux Subject RIV: EE - Microbiology, Virology Impact factor: 3.818, year: 2005

  19. LBA-ECO LC-39 Modeled Carbon Flux from Deforestation, Mato Grosso, Brazil: 2000-2006

    Data.gov (United States)

    National Aeronautics and Space Administration — This data set contains modeled estimates of carbon flux, biomass, and annual burning emissions across the Brazilian state of Mato Grosso from 2000-2006. The model,...

  20. Using Flux Information at Surface Water Boundaries to Improve a Groundwater Flow and Transport Model

    National Research Council Canada - National Science Library

    Genereux, David

    2000-01-01

    We investigated the performance of a groundwater flow and solute transport model when different combinations of hydraulic head, seepage flux, and chloride concentration data were used in calibration of the model...

  1. Evapotranspiration and heat fluxes over a patchy forest - studied using modelling and measurements

    DEFF Research Database (Denmark)

    Sogachev, Andrey; Dellwik, Ebba; Boegh, Eva

    using these parameters without a proper interpretation in mesoscale or global circulation models can results in serious bias of estimates of modelled evapotranspiration or heat fluxes from given area. Since representative measurements focused on heterogeneous effects are scarce numerical modelling can...... and latent heat flux above forest downwind of a forest edge show these fluxes to be larger than the available energy over the forest (Klaassen et al. 2002, Theor. Appl. Climatol. 72, 231-243). Because such flux measurements are very often used for calibration of forest parameters or model constants, further......, Ecological. Appl. 18, 1454-1459). In the present work, we apply the SCADIS with enhanced turbulence closure including buoyancy for investigation of the spatial distribution of latent and sensible heat vertical fluxes over patchy forested terrain in Denmark during selected days in the summer period. A closer...

  2. A Comparison Between Gravity Wave Momentum Fluxes in Observations and Climate Models

    Science.gov (United States)

    Geller, Marvin A.; Alexadner, M. Joan; Love, Peter T.; Bacmeister, Julio; Ern, Manfred; Hertzog, Albert; Manzini, Elisa; Preusse, Peter; Sato, Kaoru; Scaife, Adam A.; hide

    2013-01-01

    For the first time, a formal comparison is made between gravity wave momentum fluxes in models and those derived from observations. Although gravity waves occur over a wide range of spatial and temporal scales, the focus of this paper is on scales that are being parameterized in present climate models, sub-1000-km scales. Only observational methods that permit derivation of gravity wave momentum fluxes over large geographical areas are discussed, and these are from satellite temperature measurements, constant-density long-duration balloons, and high-vertical-resolution radiosonde data. The models discussed include two high-resolution models in which gravity waves are explicitly modeled, Kanto and the Community Atmosphere Model, version 5 (CAM5), and three climate models containing gravity wave parameterizations,MAECHAM5, Hadley Centre Global Environmental Model 3 (HadGEM3), and the Goddard Institute for Space Studies (GISS) model. Measurements generally show similar flux magnitudes as in models, except that the fluxes derived from satellite measurements fall off more rapidly with height. This is likely due to limitations on the observable range of wavelengths, although other factors may contribute. When one accounts for this more rapid fall off, the geographical distribution of the fluxes from observations and models compare reasonably well, except for certain features that depend on the specification of the nonorographic gravity wave source functions in the climate models. For instance, both the observed fluxes and those in the high-resolution models are very small at summer high latitudes, but this is not the case for some of the climate models. This comparison between gravity wave fluxes from climate models, high-resolution models, and fluxes derived from observations indicates that such efforts offer a promising path toward improving specifications of gravity wave sources in climate models.

  3. On the physical air-sea fluxes for climate modeling

    NARCIS (Netherlands)

    Bonekamp, J.G.

    2001-01-01

    At the sea surface, the atmosphere and the ocean exchange momentum, heat and freshwater. Mechanisms for the exchange are wind stress, turbulent mixing, radiation, evaporation and precipitation. These surface fluxes are characterized by a large spatial and temporal variability and play an

  4. An extended rational thermodynamics model for surface excess fluxes

    NARCIS (Netherlands)

    Sagis, L.M.C.

    2012-01-01

    In this paper, we derive constitutive equations for the surface excess fluxes in multiphase systems, in the context of an extended rational thermodynamics formalism. This formalism allows us to derive Maxwell–Cattaneo type constitutive laws for the surface extra stress tensor, the surface thermal

  5. Dissolved organic matter and lake metabolism: Biogeochemistry and controls of nutrient flux dynamics to fresh waters. Technical progress report, January 1, 1990--December 31, 1991

    Energy Technology Data Exchange (ETDEWEB)

    Wetzel, R.G.

    1992-12-31

    The land-water interface region consists of two major components: the wetland, and the down-gradient adjacent littoral floating-leaved and submersed, macrophyte communities. Because of the importance of very high production and nutrient turnover of attached microbiota, a major emphasis of this investigation was placed upon these biota and their metabolic capacities for assimilation and release of organic compounds and nutrient retention and cycling. Examination of the capacities of wetland littoral communities to regulate fluxes of nutrients and organic compounds often has been limited to input-output analyses. These input-output data are an integral part of these investigations, but most of the research effort concentrated on the biotic and metabolic mechanisms that control fluxes and retention capacities and their effects upon biota in the down-gradient waters. The important regulatory capacities of dissolved organic compounds on enzyme reactivity was examined experimentally and coupled to the wetland-littoral organic carbon flux budgets.

  6. A theoretical critical heat flux model for low-pressure, low-mass-flux, and low-steam quality conditions

    International Nuclear Information System (INIS)

    Weihsiao Ho; Kuanchywan Tu; Baushei Pei; Chinjang Chang

    1993-01-01

    The critical heat flux (CHF) is the maximum heat flux just before a boiling crisis; its importance as a measurement of nuclear reactor power capability design as well as in the safety of reactors has been recognized. With emphasis on CHF behavior under subcooled and low-quality (i.e., 2 ·s), an improved model that uses the sublayer dry out theory has been developed. Based on experimental observations of CHF, the model assumes that CHF under such conditions is of the departure from nucleate boiling type. Based on the postulation that CHF is triggered by Helmholtz instability in the sublayer steam-liquid system, the model was developed by a simple energy balance of liquid sublayer evaporation as the vapor blanket tends to disturb the balance between the buoyancy force and the drag force exerted upon it. The model is compared with the well-known Biasi et al. correlation as well as the Atomic Energy of Canada Limited lookup table against 102 uniformly heated round tube CHF data and 34 nonuniformly heated round tube CHF data. The comparison shows that the model provides better accuracy and a reasonable agreement between the predicted values and experimental CHF data

  7. Spatial Interpretation of Tower, Chamber and Modelled Terrestrial Fluxes in a Tropical Forest Plantation

    Science.gov (United States)

    Whidden, E.; Roulet, N.

    2003-04-01

    Interpretation of a site average terrestrial flux may be complicated in the presence of inhomogeneities. Inhomogeneity may invalidate the basic assumptions of aerodynamic flux measurement. Chamber measurement may miss or misinterpret important temporal or spatial anomalies. Models may smooth over important nonlinearities depending on the scale of application. Although inhomogeneity is usually seen as a design problem, many sites have spatial variance that may have a large impact on net flux, and in many cases a large homogeneous surface is unrealistic. The sensitivity and validity of a site average flux are investigated in the presence of an inhomogeneous site. Directional differences are used to evaluate the validity of aerodynamic methods and the computation of a site average tower flux. Empirical and modelling methods are used to interpret the spatial controls on flux. An ecosystem model, Ecosys, is used to assess spatial length scales appropriate to the ecophysiologic controls. A diffusion model is used to compare tower, chamber, and model data, by spatially weighting contributions within the tower footprint. Diffusion model weighting is also used to improve tower flux estimates by producing footprint averaged ecological parameters (soil moisture, soil temperature, etc.). Although uncertainty remains in the validity of measurement methods and the accuracy of diffusion models, a detailed spatial interpretation is required at an inhomogeneous site. Flux estimation between methods improves with spatial interpretation, showing the importance to an estimation of a site average flux. Small-scale temporal and spatial anomalies may be relatively unimportant to overall flux, but accounting for medium-scale differences in ecophysiological controls is necessary. A combination of measurements and modelling can be used to define the appropriate time and length scales of significant non-linearity due to inhomogeneity.

  8. HyFlux - Part I: Regional Modeling of Methane Flux From Near-Seafloor Gas Hydrate Deposits on Continental Margins

    Science.gov (United States)

    MacDonald, I. R.; Asper, V.; Garcia, O. P.; Kastner, M.; Leifer, I.; Naehr, T.; Solomon, E.; Yvon-Lewis, S.; Zimmer, B.

    2008-12-01

    HyFlux - Part I: Regional modeling of methane flux from near-seafloor gas hydrate deposits on continental margins MacDonald, I.R., Asper, V., Garcia, O., Kastner, M., Leifer, I., Naehr, T.H., Solomon, E., Yvon-Lewis, S., and Zimmer, B. The Dept. of Energy National Energy Technology Laboratory (DOE/NETL) has recently awarded a project entitled HyFlux: "Remote sensing and sea-truth measurements of methane flux to the atmosphere." The project will address this problem with a combined effort of satellite remote sensing and data collection at proven sites in the Gulf of Mexico where gas hydrate releases gas to the water column. Submarine gas hydrate is a large pool of greenhouse gas that may interact with the atmosphere over geologic time to affect climate cycles. In the near term, the magnitude of methane reaching the atmosphere from gas hydrate on continental margins is poorly known because 1) gas hydrate is exposed to metastable oceanic conditions in shallow, dispersed deposits that are poorly imaged by standard geophysical techniques and 2) the consumption of methane in marine sediments and in the water column is subject to uncertainty. The northern GOM is a prolific hydrocarbon province where rapid migration of oil, gases, and brines from deep subsurface petroleum reservoirs occurs through faults generated by salt tectonics. Focused expulsion of hydrocarbons is manifested at the seafloor by gas vents, gas hydrates, oil seeps, chemosynthetic biological communities, and mud volcanoes. Where hydrocarbon seeps occur in depths below the hydrate stability zone (~500m), rapid flux of gas will feed shallow deposits of gas hydrate that potentially interact with water column temperature changes; oil released from seeps forms sea-surface features that can be detected in remote-sensing images. The regional phase of the project will quantify verifiable sources of methane (and oil) the Gulf of Mexico continental margin and selected margins (e.g. Pakistan Margin, South China Sea

  9. Model of the buildup effect on the photon flux over a cylinder

    International Nuclear Information System (INIS)

    Mangussi, J.

    2011-01-01

    In this work, the photon flux over a cylinder surrounded by an homogeneous and isotropic medium is studied; the gamma field is produced by a radioactive point source. A model for the photon flux that reach the cylinder calculation is developed. The model is applied when the medium is vacuum and when the medium is water. The model includes the secondary photons generated by Compton scattering in the water. The model reliable and it is verified by experimental data. The high dependence on the geometry conditions of the build up flux is corroborated. (author) [es

  10. Metabolic network modeling of microbial interactions in natural and engineered environmental systems

    Directory of Open Access Journals (Sweden)

    Octavio ePerez-Garcia

    2016-05-01

    Full Text Available We review approaches to characterize metabolic interactions within microbial communities using Stoichiometric Metabolic Network (SMN models for applications in environmental and industrial biotechnology. SMN models are computational tools used to evaluate the metabolic engineering potential of various organisms. They have successfully been applied to design and optimize the microbial production of antibiotics, alcohols and amino acids by single strains. To date however, such models have been rarely applied to analyze and control the metabolism of more complex microbial communities. This is largely attributed to the diversity of microbial community functions, metabolisms and interactions. Here, we firstly review different types of microbial interaction and describe their relevance for natural and engineered environmental processes. Next, we provide a general description of the essential methods of the SMN modeling workflow including the steps of network reconstruction, simulation through Flux Balance Analysis (FBA, experimental data gathering, and model calibration. Then we broadly describe and compare four approaches to model microbial interactions using metabolic networks, i.e. i lumped networks, ii compartment per guild networks, iii bi-level optimization simulations and iv dynamic-SMN methods. These approaches can be used to integrate and analyze diverse microbial physiology, ecology and molecular community data. All of them (except the lumped approach are suitable for incorporating species abundance data but so far they have been used only to model simple communities of two to eight different species. Interactions based on substrate exchange and competition can be directly modeled using the above approaches. However, interactions based on metabolic feedbacks, such as product inhibition and synthropy require extensions to current models, incorporating gene regulation and compounding accumulation mechanisms. SMN models of microbial

  11. Modelling bidirectional fluxes of methanol and acetaldehyde with the FORCAsT canopy exchange model

    Directory of Open Access Journals (Sweden)

    K. Ashworth

    2016-12-01

    Full Text Available The FORCAsT canopy exchange model was used to investigate the underlying mechanisms governing foliage emissions of methanol and acetaldehyde, two short chain oxygenated volatile organic compounds ubiquitous in the troposphere and known to have strong biogenic sources, at a northern mid-latitude forest site. The explicit representation of the vegetation canopy within the model allowed us to test the hypothesis that stomatal conductance regulates emissions of these compounds to an extent that its influence is observable at the ecosystem scale, a process not currently considered in regional- or global-scale atmospheric chemistry models.We found that FORCAsT could only reproduce the magnitude and diurnal profiles of methanol and acetaldehyde fluxes measured at the top of the forest canopy at Harvard Forest if light-dependent emissions were introduced to the model. With the inclusion of such emissions, FORCAsT was able to successfully simulate the observed bidirectional exchange of methanol and acetaldehyde. Although we found evidence that stomatal conductance influences methanol fluxes and concentrations at scales beyond the leaf level, particularly at dawn and dusk, we were able to adequately capture ecosystem exchange without the addition of stomatal control to the standard parameterisations of foliage emissions, suggesting that ecosystem fluxes can be well enough represented by the emissions models currently used.

  12. Optimized numerical annular flow dryout model using the drift-flux model in tube geometry

    International Nuclear Information System (INIS)

    Chun, Ji Han; Lee, Un Chul

    2008-01-01

    Many experimental analyses for annular film dryouts, which is one of the Critical Heat Flux (CHF) mechanisms, have been performed because of their importance. Numerical approaches must also be developed in order to assess the results from experiments and to perform pre-tests before experiments. Various thermal-hydraulic codes, such as RELAP, COBRATF, MARS, etc., have been used in the assessment of the results of dryout experiments and in experimental pre-tests. These thermal-hydraulic codes are general tools intended for the analysis of various phenomena that could appear in nuclear power plants, and many models applying these codes are unnecessarily complex for the focused analysis of dryout phenomena alone. In this study, a numerical model was developed for annular film dryout using the drift-flux model from uniform heated tube geometry. Several candidates of models that strongly affect dryout, such as the entrainment model, deposition model, and the criterion for the dryout point model, were tested as candidates for inclusion in an optimized annular film dryout model. The optimized model was developed by adopting the best combination of these candidate models, as determined through comparison with experimental data. This optimized model showed reasonable results, which were better than those of MARS code

  13. Next-generation genome-scale models for metabolic engineering

    DEFF Research Database (Denmark)

    King, Zachary A.; Lloyd, Colton J.; Feist, Adam M.

    2015-01-01

    Constraint-based reconstruction and analysis (COBRA) methods have become widely used tools for metabolic engineering in both academic and industrial laboratories. By employing a genome-scale in silico representation of the metabolic network of a host organism, COBRA methods can be used to predict...... examples of applying COBRA methods to strain optimization are presented and discussed. Then, an outlook is provided on the next generation of COBRA models and the new types of predictions they will enable for systems metabolic engineering....

  14. Calculation of atmospheric neutrino flux using the interaction model calibrated with atmospheric muon data

    International Nuclear Information System (INIS)

    Honda, M.; Kajita, T.; Kasahara, K.; Midorikawa, S.; Sanuki, T.

    2007-01-01

    Using the 'modified DPMJET-III' model explained in the previous paper [T. Sanuki et al., preceding Article, Phys. Rev. D 75, 043005 (2007).], we calculate the atmospheric neutrino flux. The calculation scheme is almost the same as HKKM04 [M. Honda, T. Kajita, K. Kasahara, and S. Midorikawa, Phys. Rev. D 70, 043008 (2004).], but the usage of the 'virtual detector' is improved to reduce the error due to it. Then we study the uncertainty of the calculated atmospheric neutrino flux summarizing the uncertainties of individual components of the simulation. The uncertainty of K-production in the interaction model is estimated using other interaction models: FLUKA'97 and FRITIOF 7.02, and modifying them so that they also reproduce the atmospheric muon flux data correctly. The uncertainties of the flux ratio and zenith angle dependence of the atmospheric neutrino flux are also studied

  15. The truth is out there: measured, calculated and modelled benthic fluxes.

    Science.gov (United States)

    Pakhomova, Svetlana; Protsenko, Elizaveta

    2016-04-01

    In a modern Earth science there is a great importance of understanding the processes, forming the benthic fluxes as one of element sources or sinks to or from the water body, which affects the elements balance in the water system. There are several ways to assess benthic fluxes and here we try to compare the results obtained by chamber experiments, calculated from porewater distributions and simulated with model. Benthic fluxes of dissolved elements (oxygen, nitrogen species, phosphate, silicate, alkalinity, iron and manganese species) were studied in the Baltic and Black Seas from 2000 to 2005. Fluxes were measured in situ using chamber incubations (Jch) and at the same time sediment cores were collected to assess the porewater distribution at different depths to calculate diffusive fluxes (Jpw). Model study was carried out with benthic-pelagic biogeochemical model BROM (O-N-P-Si-C-S-Mn-Fe redox model). It was applied to simulate biogeochemical structure of the water column and upper sediment and to assess the vertical fluxes (Jmd). By the behaviour at the water-sediment interface all studied elements can be divided into three groups: (1) elements which benthic fluxes are determined by the concentrations gradient only (Si, Mn), (2) elements which fluxes depend on redox conditions in the bottom water (Fe, PO4, NH4), and (3) elements which fluxes are strongly connected with organic matter fate (O2, Alk, NH4). For the first group it was found that measured fluxes are always higher than calculated diffusive fluxes (1.5disadvantages and the main facing us question is - which value should be taken for calculation the balance? This research is funded by VISTA - a basic research program and collaborative partnership between the Norwegian Academy of Science and Letters and Statoil.

  16. Simulation of upward flux from shallow water-table using UPFLOW model

    Directory of Open Access Journals (Sweden)

    M. H. Ali

    2013-11-01

    Full Text Available The upward movement of water by capillary rise from shallow water-table to the root zone is an important incoming flux. For determining exact amount of irrigation requirement, estimation of capillary flux or upward flux is essential. Simulation model can provide a reliable estimate of upward flux under variable soil and climatic conditions. In this study, the performance of model UPFLOW to estimate upward flux was evaluated. Evaluation of model performance was performed with both graphical display and statistical criteria. In distribution of simulated capillary rise values against observed field data, maximum data points lie around the 1:1 line, which means that the model output is reliable and reasonable. The coefficient of determination between observed and simulated values was 0.806 (r = 0.93, which indicates a good inter-relation between observed and simulated values. The relative error, model efficiency, and index of agreement were found as 27.91%, 85.93% and 0.96, respectively. Considering the graphical display of observed and simulated upward flux and statistical indicators, it can be concluded that the overall performance of the UPFLOW model in simulating actual upward flux from a crop field under variable water-table condition is satisfactory. Thus, the model can be used to estimate capillary rise from shallow water-table for proper estimation of irrigation requirement, which would save valuable water from over-irrigation.

  17. A simple model of the distant Jovian tail with magnetic flux loss

    International Nuclear Information System (INIS)

    Grzedzielski, S.; Macek, W.; Oberc, P.

    1982-01-01

    The influence of a small rate of magnetic flux loss on a simple hydromagnetic model of the distant Jovian tail was estimated. The loss of flux leads to a 10-15% decrease of the tail radius at Saturn's distance. Possible encounter of the tail with Uranus in 1983 is also briefly discussed. (author)

  18. Inverse modeling of hydrologic parameters using surface flux and runoff observations in the Community Land Model

    Science.gov (United States)

    Sun, Y.; Hou, Z.; Huang, M.; Tian, F.; Leung, L. Ruby

    2013-12-01

    This study demonstrates the possibility of inverting hydrologic parameters using surface flux and runoff observations in version 4 of the Community Land Model (CLM4). Previous studies showed that surface flux and runoff calculations are sensitive to major hydrologic parameters in CLM4 over different watersheds, and illustrated the necessity and possibility of parameter calibration. Both deterministic least-square fitting and stochastic Markov-chain Monte Carlo (MCMC)-Bayesian inversion approaches are evaluated by applying them to CLM4 at selected sites with different climate and soil conditions. The unknowns to be estimated include surface and subsurface runoff generation parameters and vadose zone soil water parameters. We find that using model parameters calibrated by the sampling-based stochastic inversion approaches provides significant improvements in the model simulations compared to using default CLM4 parameter values, and that as more information comes in, the predictive intervals (ranges of posterior distributions) of the calibrated parameters become narrower. In general, parameters that are identified to be significant through sensitivity analyses and statistical tests are better calibrated than those with weak or nonlinear impacts on flux or runoff observations. Temporal resolution of observations has larger impacts on the results of inverse modeling using heat flux data than runoff data. Soil and vegetation cover have important impacts on parameter sensitivities, leading to different patterns of posterior distributions of parameters at different sites. Overall, the MCMC-Bayesian inversion approach effectively and reliably improves the simulation of CLM under different climates and environmental conditions. Bayesian model averaging of the posterior estimates with different reference acceptance probabilities can smooth the posterior distribution and provide more reliable parameter estimates, but at the expense of wider uncertainty bounds.

  19. Neuro-fuzzy model of homocysteine metabolism

    Indian Academy of Sciences (India)

    To conclude, polymorphisms in genes regulating remethylation of homocysteine strongly influence homocysteine levels. The restoration of one-carbon homeostasis by SHMT1 C1420T or increased flux of folate towards remethylation due to TYMS 5'-UTR 28 bp tandem repeat or nonvegetariandiet can lower homocysteine ...

  20. Co-factor engineering in lactobacilli: Effects of uncoupled ATPase activity on metabolic fluxes in Lactobacillus (L.) plantarum and L. sakei

    DEFF Research Database (Denmark)

    Rud, Ida; Solem, Christian; Jensen, Peter Ruhdal

    2008-01-01

    The hydrolytic F-1-part of the F1F0-ATPase was over-expressed in Lactobacillus (L.) plantarum NC8 and L. sakei Lb790x during fermentation of glucose or ribose, in order to study how changes in the intracellular levels of ATP and ADP affect the metabolic fluxes. The uncoupled ATPase activity...... resulted in a decrease in intracellular energy level (ATP/ADP ratio), biomass yield and growth rate. Interestingly, the glycolytic and ribolytic flux increased in L. plantarum with uncoupled ATPase activity compared to the reference strain by up to 20% and 50%, respectively. The ATP demand was estimated...... to have approximately 80% control on both the glycolytic and ribolytic flux in L. plantarum under these conditions. In contrast, the glycolytic and ribolytic flux decreased in L. sakei with uncoupled ATPase activity. (C) 2008 Elsevier Inc. All rights reserved....

  1. Modeling the Effects of Meteorological Conditions on the Neutron Flux

    Science.gov (United States)

    2017-05-22

    about 2% between day and night on a given day [2]. In the 1960s, the launch of satellites allowed scientists to measure the sun’s cosmic rays outside...hour, a 20% variation, over five months of data collection with large variation between days . Meteorological data were collected with two commercially...contributes to the formation of the neutron flux. To account for the earth’s magnetic field, scientists have done extensive three-dimensional analysis

  2. Modeling the Solar Convective Dynamo and Emerging Flux

    Science.gov (United States)

    Fan, Y.

    2017-12-01

    Significant advances have been made in recent years in global-scale fully dynamic three-dimensional convective dynamo simulations of the solar/stellar convective envelopes to reproduce some of the basic features of the Sun's large-scale cyclic magnetic field. It is found that the presence of the dynamo-generated magnetic fields plays an important role for the maintenance of the solar differential rotation, without which the differential rotation tends to become anti-solar (with a faster rotating pole instead of the observed faster rotation at the equator). Convective dynamo simulations are also found to produce emergence of coherent super-equipartition toroidal flux bundles with a statistically significant mean tilt angle that is consistent with the mean tilt of solar active regions. The emerging flux bundles are sheared by the giant cell convection into a forward leaning loop shape with its leading side (in the direction of rotation) pushed closer to the strong downflow lanes. Such asymmetric emerging flux pattern may lead to the observed asymmetric properties of solar active regions.

  3. Magnetic Flux Rope Identification and Characterization from Observationally Driven Solar Coronal Models

    Science.gov (United States)

    Lowder, Chris; Yeates, Anthony

    2017-09-01

    Formed through magnetic field shearing and reconnection in the solar corona, magnetic flux ropes are structures of twisted magnetic field, threaded along an axis. Their evolution and potential eruption are of great importance for space weather. Here we describe a new methodology for the automated detection of flux ropes in simulated magnetic fields, utilizing field-line helicity. Our Flux Rope Detection and Organization (FRoDO) code, which measures the magnetic flux and helicity content of pre-erupting flux ropes over time, as well as detecting eruptions, is publicly available. As a first demonstration, the code is applied to the output from a time-dependent magnetofrictional model, spanning 1996 June 15-2014 February 10. Over this period, 1561 erupting and 2099 non-erupting magnetic flux ropes are detected, tracked, and characterized. For this particular model data, erupting flux ropes have a mean net helicity magnitude of 2.66× {10}43 Mx2, while non-erupting flux ropes have a significantly lower mean of 4.04× {10}42 Mx2, although there is overlap between the two distributions. Similarly, the mean unsigned magnetic flux for erupting flux ropes is 4.04× {10}21 Mx, significantly higher than the mean value of 7.05× {10}20 Mx for non-erupting ropes. These values for erupting flux ropes are within the broad range expected from observational and theoretical estimates, although the eruption rate in this particular model is lower than that of observed coronal mass ejections. In the future, the FRoDO code will prove to be a valuable tool for assessing the performance of different non-potential coronal simulations and comparing them with observations.

  4. 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.

  5. 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

  6. Reconstruction and analysis of a genome-scale metabolic model for Scheffersomyces stipitis

    Directory of Open Access Journals (Sweden)

    Balagurunathan Balaji

    2012-02-01

    Full Text Available Abstract Background Fermentation of xylose, the major component in hemicellulose, is essential for economic conversion of lignocellulosic biomass to fuels and chemicals. The yeast Scheffersomyces stipitis (formerly known as Pichia stipitis has the highest known native capacity for xylose fermentation and possesses several genes for lignocellulose bioconversion in its genome. Understanding the metabolism of this yeast at a global scale, by reconstructing the genome scale metabolic model, is essential for manipulating its metabolic capabilities and for successful transfer of its capabilities to other industrial microbes. Results We present a genome-scale metabolic model for Scheffersomyces stipitis, a native xylose utilizing yeast. The model was reconstructed based on genome sequence annotation, detailed experimental investigation and known yeast physiology. Macromolecular composition of Scheffersomyces stipitis biomass was estimated experimentally and its ability to grow on different carbon, nitrogen, sulphur and phosphorus sources was determined by phenotype microarrays. The compartmentalized model, developed based on an iterative procedure, accounted for 814 genes, 1371 reactions, and 971 metabolites. In silico computed growth rates were compared with high-throughput phenotyping data and the model could predict the qualitative outcomes in 74% of substrates investigated. Model simulations were used to identify the biosynthetic requirements for anaerobic growth of Scheffersomyces stipitis on glucose and the results were validated with published literature. The bottlenecks in Scheffersomyces stipitis metabolic network for xylose uptake and nucleotide cofactor recycling were identified by in silico flux variability analysis. The scope of the model in enhancing the mechanistic understanding of microbial metabolism is demonstrated by identifying a mechanism for mitochondrial respiration and oxidative phosphorylation. Conclusion The genome

  7. An accurate description of Aspergillus niger organic acid batch fermentation through dynamic metabolic modelling.

    Science.gov (United States)

    Upton, Daniel J; McQueen-Mason, Simon J; Wood, A Jamie

    2017-01-01

    Aspergillus niger fermentation has provided the chief source of industrial citric acid for over 50 years. Traditional strain development of this organism was achieved through random mutagenesis, but advances in genomics have enabled the development of genome-scale metabolic modelling that can be used to make predictive improvements in fermentation performance. The parent citric acid-producing strain of A. niger , ATCC 1015, has been described previously by a genome-scale metabolic model that encapsulates its response to ambient pH. Here, we report the development of a novel double optimisation modelling approach that generates time-dependent citric acid fermentation using dynamic flux balance analysis. The output from this model shows a good match with empirical fermentation data. Our studies suggest that citric acid production commences upon a switch to phosphate-limited growth and this is validated by fitting to empirical data, which confirms the diauxic growth behaviour and the role of phosphate storage as polyphosphate. The calibrated time-course model reflects observed metabolic events and generates reliable in silico data for industrially relevant fermentative time series, and for the behaviour of engineered strains suggesting that our approach can be used as a powerful tool for predictive metabolic engineering.

  8. Modelling stomatal ozone flux and deposition to grassland communities across Europe

    International Nuclear Information System (INIS)

    Ashmore, M.R.; Bueker, P.; Emberson, L.D.; Terry, A.C.; Toet, S.

    2007-01-01

    Regional scale modelling of both ozone deposition and the risk of ozone impacts is poorly developed for grassland communities. This paper presents new predictions of stomatal ozone flux to grasslands at five different locations in Europe, using a mechanistic model of canopy development for productive grasslands to generate time series of leaf area index and soil water potential as inputs to the stomatal component of the DO 3 SE ozone deposition model. The parameterisation of both models was based on Lolium perenne, a dominant species of productive pasture in Europe. The modelled seasonal time course of stomatal ozone flux to both the whole canopy and to upper leaves showed large differences between climatic zones, which depended on the timing of the start of the growing season, the effect of soil water potential, and the frequency of hay cuts. Values of modelled accumulated flux indices and the AOT40 index showed a five-fold difference between locations, but the locations with the highest flux differed depending on the index used; the period contributing to the accumulation of AOT40 did not always coincide with the modelled period of active ozone canopy uptake. Use of a fixed seasonal profile of leaf area index in the flux model produced very different estimates of annual accumulated total canopy and leaf ozone flux when compared with the flux model linked to a simulation of canopy growth. Regional scale model estimates of both the risks of ozone impacts and of total ozone deposition will be inaccurate unless the effects of climate and management in modifying grass canopy growth are incorporated. - Modelled stomatal flux of ozone to productive grasslands in Europe shows different spatial and temporal variation to AOT40, and is modified by management and soil water status

  9. Spatially explicit modeling of particulate nutrient flux in Large global rivers

    Science.gov (United States)

    Cohen, S.; Kettner, A.; Mayorga, E.; Harrison, J. A.

    2017-12-01

    Water, sediment, nutrient and carbon fluxes along river networks have undergone considerable alterations in response to anthropogenic and climatic changes, with significant consequences to infrastructure, agriculture, water security, ecology and geomorphology worldwide. However, in a global setting, these changes in fluvial fluxes and their spatial and temporal characteristics are poorly constrained, due to the limited availability of continuous and long-term observations. We present results from a new global-scale particulate modeling framework (WBMsedNEWS) that combines the Global NEWS watershed nutrient export model with the spatially distributed WBMsed water and sediment model. We compare the model predictions against multiple observational datasets. The results indicate that the model is able to accurately predict particulate nutrient (Nitrogen, Phosphorus and Organic Carbon) fluxes on an annual time scale. Analysis of intra-basin nutrient dynamics and fluxes to global oceans is presented.

  10. Assessing FPAR Source and Parameter Optimization Scheme in Application of a Diagnostic Carbon Flux Model

    Energy Technology Data Exchange (ETDEWEB)

    Turner, D P; Ritts, W D; Wharton, S; Thomas, C; Monson, R; Black, T A

    2009-02-26

    The combination of satellite remote sensing and carbon cycle models provides an opportunity for regional to global scale monitoring of terrestrial gross primary production, ecosystem respiration, and net ecosystem production. FPAR (the fraction of photosynthetically active radiation absorbed by the plant canopy) is a critical input to diagnostic models, however little is known about the relative effectiveness of FPAR products from different satellite sensors nor about the sensitivity of flux estimates to different parameterization approaches. In this study, we used multiyear observations of carbon flux at four eddy covariance flux tower sites within the conifer biome to evaluate these factors. FPAR products from the MODIS and SeaWiFS sensors, and the effects of single site vs. cross-site parameter optimization were tested with the CFLUX model. The SeaWiFs FPAR product showed greater dynamic range across sites and resulted in slightly reduced flux estimation errors relative to the MODIS product when using cross-site optimization. With site-specific parameter optimization, the flux model was effective in capturing seasonal and interannual variation in the carbon fluxes at these sites. The cross-site prediction errors were lower when using parameters from a cross-site optimization compared to parameter sets from optimization at single sites. These results support the practice of multisite optimization within a biome for parameterization of diagnostic carbon flux models.

  11. Validation of the doubly-labeled water (H3H18O) method for measuring water flux and energy metabolism in tenebrionid beetles

    International Nuclear Information System (INIS)

    Cooper, P.D.

    1981-01-01

    Doubly-labeled water (H 3 H 18 O) has been used to determine water flux and energy metabolism in a variety of vertebrates. This study examines the applicability of this technique to arthropods. The theory of the technique depends upon the assumption that doubly-labeled water introduced into the animal's body water equilibrates with water and carbon dioxide by the action of carbonic anhydrase. Tritium ( 3 H) is lost from the animal only with water while oxygen-18 is lost with both water and carbon dioxide. The difference bwtween the rates of loss of the two isotopes is proportional to CO 2 loss rate. Validation of the use of tritiated water for measuring water flux was accomplished by comparing gravimetric measurements of water gain with flux rates determined by loss of tritiated water. At room humidity, an overestimate for influx calculated from labeled water calculations was found, averaging 12 mg H 2 O (g.d) -1 . Comparison of CO 2 loss rate determined isotopically with rates of CO 2 loss determined by standard metabolic rates also yielded overestimates for the isotopic technique, overestimates ranging between 20 and 30%. The relevance of this for studies using labeled water for studying water fluxes and free metabolism of free-ranging arthropods is discussed

  12. Modeling and Predicting Carbon and Water Fluxes Using Data-Driven Techniques in a Forest Ecosystem

    Directory of Open Access Journals (Sweden)

    Xianming Dou

    2017-12-01

    Full Text Available Accurate estimation of carbon and water fluxes of forest ecosystems is of particular importance for addressing the problems originating from global environmental change, and providing helpful information about carbon and water content for analyzing and diagnosing past and future climate change. The main focus of the current work was to investigate the feasibility of four comparatively new methods, including generalized regression neural network, group method of data handling (GMDH, extreme learning machine and adaptive neuro-fuzzy inference system (ANFIS, for elucidating the carbon and water fluxes in a forest ecosystem. A comparison was made between these models and two widely used data-driven models, artificial neural network (ANN and support vector machine (SVM. All the models were evaluated based on the following statistical indices: coefficient of determination, Nash-Sutcliffe efficiency, root mean square error and mean absolute error. Results indicated that the data-driven models are capable of accounting for most variance in each flux with the limited meteorological variables. The ANN model provided the best estimates for gross primary productivity (GPP and net ecosystem exchange (NEE, while the ANFIS model achieved the best for ecosystem respiration (R, indicating that no single model was consistently superior to others for the carbon flux prediction. In addition, the GMDH model consistently produced somewhat worse results for all the carbon flux and evapotranspiration (ET estimations. On the whole, among the carbon and water fluxes, all the models produced similar highly satisfactory accuracy for GPP, R and ET fluxes, and did a reasonable job of reproducing the eddy covariance NEE. Based on these findings, it was concluded that these advanced models are promising alternatives to ANN and SVM for estimating the terrestrial carbon and water fluxes.

  13. The interaction of the flux errors and transport errors in modeled atmospheric carbon dioxide concentrations

    Science.gov (United States)

    Feng, S.; Lauvaux, T.; Butler, M. P.; Keller, K.; Davis, K. J.; Jacobson, A. R.; Schuh, A. E.; Basu, S.; Liu, J.; Baker, D.; Crowell, S.; Zhou, Y.; Williams, C. A.

    2017-12-01

    Regional estimates of biogenic carbon fluxes over North America from top-down atmospheric inversions and terrestrial biogeochemical (or bottom-up) models remain inconsistent at annual and sub-annual time scales. While top-down estimates are impacted by limited atmospheric data, uncertain prior flux estimates and errors in the atmospheric transport models, bottom-up fluxes are affected by uncertain driver data, uncertain model parameters and missing mechanisms across ecosystems. This study quantifies both flux errors and transport errors, and their interaction in the CO2 atmospheric simulation. These errors are assessed by an ensemble approach. The WRF-Chem model is set up with 17 biospheric fluxes from the Multiscale Synthesis and Terrestrial Model Intercomparison Project, CarbonTracker-Near Real Time, and the Simple Biosphere model. The spread of the flux ensemble members represents the flux uncertainty in the modeled CO2 concentrations. For the transport errors, WRF-Chem is run using three physical model configurations with three stochastic perturbations to sample the errors from both the physical parameterizations of the model and the initial conditions. Additionally, the uncertainties from boundary conditions are assessed using four CO2 global inversion models which have assimilated tower and satellite CO2 observations. The error structures are assessed in time and space. The flux ensemble members overall overestimate CO2 concentrations. They also show larger temporal variability than the observations. These results suggest that the flux ensemble is overdispersive. In contrast, the transport ensemble is underdispersive. The averaged spatial distribution of modeled CO2 shows strong positive biogenic signal in the southern US and strong negative signals along the eastern coast of Canada. We hypothesize that the former is caused by the 3-hourly downscaling algorithm from which the nighttime respiration dominates the daytime modeled CO2 signals and that the latter

  14. Neuro-fuzzy model of homocysteine metabolism

    Indian Academy of Sciences (India)

    SHAIK Mohammad Naushad

    2017-12-08

    Dec 8, 2017 ... Homocysteine is a nondietary amino acid, which is the byproduct of ... wide spectrum of diseases such as recurrent pregnancy loss (Govindaiah et al. ... A2756G, MTRR A66G were reported in the folate metabolic pathway ...

  15. LBA-ECO LC-39 Modeled Carbon Flux from Deforestation, Mato Grosso, Brazil: 2000-2006

    Data.gov (United States)

    National Aeronautics and Space Administration — ABSTRACT: This data set contains modeled estimates of carbon flux, biomass, and annual burning emissions across the Brazilian state of Mato Grosso from 2000-2006....

  16. Testing of models of stomatal ozone fluxes with field measurements in a mixed Mediterranean forest

    Czech Academy of Sciences Publication Activity Database

    Fares, S.; Matteucci, G.; Mugnozza, S.; Morani, A.; Calfapietra, Carlo; Salvatori, E.; Fusaro, L.; Manes, F.; Loreto, F.

    2013-01-01

    Roč. 67, MAR (2013), s. 242-251 ISSN 1352-2310 Institutional support: RVO:67179843 Keywords : Ozone fluxes * Stomatal conductance models * GPP * Mediterranean forest Subject RIV: EH - Ecology, Behaviour Impact factor: 3.062, year: 2013

  17. Reframed Genome-Scale Metabolic Model to Facilitate Genetic Design and Integration with Expression Data.

    Science.gov (United States)

    Gu, Deqing; Jian, Xingxing; Zhang, Cheng; Hua, Qiang

    2017-01-01

    Genome-scale metabolic network models (GEMs) have played important roles in the design of genetically engineered strains and helped biologists to decipher metabolism. However, due to the complex gene-reaction relationships that exist in model systems, most algorithms have limited capabilities with respect to directly predicting accurate genetic design for metabolic engineering. In particular, methods that predict reaction knockout strategies leading to overproduction are often impractical in terms of gene manipulations. Recently, we proposed a method named logical transformation of model (LTM) to simplify the gene-reaction associations by introducing intermediate pseudo reactions, which makes it possible to generate genetic design. Here, we propose an alternative method to relieve researchers from deciphering complex gene-reactions by adding pseudo gene controlling reactions. In comparison to LTM, this new method introduces fewer pseudo reactions and generates a much smaller model system named as gModel. We showed that gModel allows two seldom reported applications: identification of minimal genomes and design of minimal cell factories within a modified OptKnock framework. In addition, gModel could be used to integrate expression data directly and improve the performance of the E-Fmin method for predicting fluxes. In conclusion, the model transformation procedure will facilitate genetic research based on GEMs, extending their applications.

  18. Network Thermodynamic Curation of Human and Yeast Genome-Scale Metabolic Models

    Science.gov (United States)

    Martínez, Verónica S.; Quek, Lake-Ee; Nielsen, Lars K.

    2014-01-01

    Genome-scale models are used for an ever-widening range of applications. Although there has been much focus on specifying the stoichiometric matrix, the predictive power of genome-scale models equally depends on reaction directions. Two-thirds of reactions in the two eukaryotic reconstructions Homo sapiens Recon 1 and Yeast 5 are specified as irreversible. However, these specifications are mainly based on biochemical textbooks or on their similarity to other organisms and are rarely underpinned by detailed thermodynamic analysis. In this study, a to our knowledge new workflow combining network-embedded thermodynamic and flux variability analysis was used to evaluate existing irreversibility constraints in Recon 1 and Yeast 5 and to identify new ones. A total of 27 and 16 new irreversible reactions were identified in Recon 1 and Yeast 5, respectively, whereas only four reactions were found with directions incorrectly specified against thermodynamics (three in Yeast 5 and one in Recon 1). The workflow further identified for both models several isolated internal loops that require further curation. The framework also highlighted the need for substrate channeling (in human) and ATP hydrolysis (in yeast) for the essential reaction catalyzed by phosphoribosylaminoimidazole carboxylase in purine metabolism. Finally, the framework highlighted differences in proline metabolism between yeast (cytosolic anabolism and mitochondrial catabolism) and humans (exclusively mitochondrial metabolism). We conclude that network-embedded thermodynamics facilitates the specification and validation of irreversibility constraints in compartmentalized metabolic models, at the same time providing further insight into network properties. PMID:25028891

  19. Prediction of transient maximum heat flux based on a simple liquid layer evaporation model

    International Nuclear Information System (INIS)

    Serizawa, A.; Kataoka, I.

    1981-01-01

    A model of liquid layer evaporation with considerable supply of liquid has been formulated to predict burnout characteristics (maximum heat flux, life, etc.) during an increase of the power. The analytical description of the model is built upon the visual and photographic observations of the boiling configuration at near peak heat flux reported by other investigators. The prediction compares very favourably with water data presently available. It is suggested from the work reported here that the maximum heat flux occurs because of a balance between the consumption of the liquid film on the heated surface and the supply of liquid. Thickness of the liquid film is also very important. (author)

  20. A workflow for mathematical modeling of subcellular metabolic pathways in leaf metabolism of Arabidopsis thaliana

    Directory of Open Access Journals (Sweden)

    Thomas eNägele

    2013-12-01

    Full Text Available During the last decade genome sequencing has experienced a rapid technological development resulting in numerous sequencing projects and applications in life science. In plant molecular biology, the availability of sequence data on whole genomes has enabled the reconstruction of metabolic networks. Enzymatic reactions are predicted by the sequence information. Pathways arise due to the participation of chemical compounds as substrates and products in these reactions. Although several of these comprehensive networks have been reconstructed for the genetic model plant Arabidopsis thaliana, the integration of experimental data is still challenging. Particularly the analysis of subcellular organization of plant cells limits the understanding of regulatory instances in these metabolic networks in vivo. In this study, we develop an approach for the functional integration of experimental high-throughput data into such large-scale networks. We present a subcellular metabolic network model comprising 524 metabolic intermediates and 548 metabolic interactions derived from a total of 2769 reactions. We demonstrate how to link the metabolite covariance matrix of different Arabidopsis thaliana accessions with the subcellular metabolic network model for the inverse calculation of the biochemical Jacobian, finally resulting in the calculation of a matrix which satisfies a Lyaponov equation involving a covariance matrix. In this way, differential strategies of metabolite compartmentation and involved reactions were identified in the accessions when exposed to low temperature.

  1. Evaluation of Latent Heat Flux Fields from Satellites and Models during SEMAPHORE.

    Science.gov (United States)

    Bourras, Denis; Liu, W. Timothy; Eymard, Laurence; Tang, Wenqing

    2003-02-01

    Latent heat fluxes were derived from satellite observations in the region of Structure des Echanges Mer-Atmosphère, Propriétés des Hétérogénéités Océaniques: Recherche Expérimentale (SEMAPHORE), which was conducted near the Azores islands in the North Atlantic Ocean in autumn of 1993. The satellite fluxes were compared with output fields of two atmospheric circulation models and in situ measurements. The rms error of the instantaneous satellite fluxes is between 35 and 40 W m-2 and the bias is 60-85 W m-2. The large bias is mainly attributed to a bias in satellite-derived atmospheric humidity and is related to the particular shape of the vertical humidity profiles during SEMAPHORE. The bias in humidity implies that the range of estimated fluxes is smaller than the range of ship fluxes, by 34%-38%. The rms errors for fluxes from models are 30-35 W m-2, and the biases are smaller than the biases in satellite fluxes (14-18 W m-2). Two case studies suggest that the satellites detect horizontal gradients of wind speed and specific humidity if the magnitude of the gradients exceeds a detection threshold, which is 1.27 g kg-1 (100 km)-1 for specific humidity and between 0.35 and 0.82 m s-1 (30 km)-1 for wind speed. In contrast, the accuracy of the spatial gradients of bulk variables from models always varies as a function of the location and number of assimilated observations. A comparison between monthly fluxes from satellites and models reveals that satellite-derived flux anomaly fields are consistent with reanalyzed fields, whereas operational model products lack part of the mesoscale structures present in the satellite fields.

  2. Application of a Subfilter-Scale Flux Model over the Ocean Using OHATS Field Data

    DEFF Research Database (Denmark)

    Kelly, Mark C.; Wyngaard, John C.; Sullivan, Peter P.

    2009-01-01

    the scalar flux model appeared to perform adequately over the ocean. Analysis of data from the Ocean Horizontal Array Turbulence Study (OHATS) reveals a need to account for the moving ocean–air interface in the subfilter stress model. The authors develop simple parameterizations for the effect of surface......-induced pressure fluctuations on the subfilter stress, leading to good predictions of subfilter momentum flux both over land and in OHATS....

  3. Constraint based modeling of metabolism allows finding metabolic cancer hallmarks and identifying personalized therapeutic windows.

    Science.gov (United States)

    Bordel, Sergio

    2018-04-13

    In order to choose optimal personalized anticancer treatments, transcriptomic data should be analyzed within the frame of biological networks. The best known human biological network (in terms of the interactions between its different components) is metabolism. Cancer cells have been known to have specific metabolic features for a long time and currently there is a growing interest in characterizing new cancer specific metabolic hallmarks. In this article it is presented a method to find personalized therapeutic windows using RNA-seq data and Genome Scale Metabolic Models. This method is implemented in the python library, pyTARG. Our predictions showed that the most anticancer selective (affecting 27 out of 34 considered cancer cell lines and only 1 out of 6 healthy mesenchymal stem cell lines) single metabolic reactions are those involved in cholesterol biosynthesis. Excluding cholesterol biosynthesis, all the considered cell lines can be selectively affected by targeting different combinations (from 1 to 5 reactions) of only 18 metabolic reactions, which suggests that a small subset of drugs or siRNAs combined in patient specific manners could be at the core of metabolism based personalized treatments.

  4. A simple heat transfer model for a heat flux plate under transient conditions

    International Nuclear Information System (INIS)

    Ryan, L.; Dale, J.D.

    1985-01-01

    Heat flux plates are used for measuring rates of heat transfer through surfaces under steady state and transient conditions. Their usual construction is to have a resistive layer bounded by thermopiles and an exterior layer for protection. If properly designed and constructed a linear relationship between the thermopile generated voltage and heat flux results and calibration under steady state conditions is straight forward. Under transient conditions however the voltage output from a heat flux plate cannot instantaneously follow the heat flux because of the thermal capacitance of the plate and the resulting time lag. In order to properly interpret the output of a heat flux plate used under transient conditions a simple heat transfer model was constructed and tested. (author)

  5. Modeling of phosphorus fluxes produced by wild fires at watershed scales.

    Science.gov (United States)

    Matyjasik, M.; Hernandez, M.; Shaw, N.; Baker, M.; Fowles, M. T.; Cisney, T. A.; Jex, A. P.; Moisen, G.

    2017-12-01

    River runoff is one of the controlling processes in the terrestrial phosphorus cycle. Phosphorus is often a limiting factor in fresh water. One of the factors that has not been studied and modeled in detail is phosporus flux produced from forest wild fires. Phosphate released by weathering is quickly absorbed in soils. Forest wild fires expose barren soils to intensive erosion, thus releasing relatively large fluxes of phosphorus. Measurements from three control burn sites were used to correlate erosion with phosphorus fluxes. These results were used to model phosphorus fluxes from burned watersheds during a five year long period after fires occurred. Erosion in our model is simulated using a combination of two models: the WEPP (USDA Water Erosion Prediction Project) and the GeoWEPP (GIS-based Water Erosion Prediction Project). Erosion produced from forest disturbances is predicted for any watershed using hydrologic, soil, and meteorological data unique to the individual watersheds or individual slopes. The erosion results are modified for different textural soil classes and slope angles to model fluxes of phosphorus. The results of these models are calibrated using measured concentrations of phosphorus for three watersheds located in the Interior Western United States. The results will help the United States Forest Service manage phosporus fluxes in national forests.

  6. Analytical Modeling of a Novel Transverse Flux Machine for Direct Drive Wind Turbine Applications: Preprint

    Energy Technology Data Exchange (ETDEWEB)

    Hasan, IIftekhar; Husain, Tausif; Uddin, Md Wasi; Sozer, Yilmaz; Husain; Iqbal; Muljadi, Eduard

    2015-08-24

    This paper presents a nonlinear analytical model of a novel double-sided flux concentrating Transverse Flux Machine (TFM) based on the Magnetic Equivalent Circuit (MEC) model. The analytical model uses a series-parallel combination of flux tubes to predict the flux paths through different parts of the machine including air gaps, permanent magnets, stator, and rotor. The two-dimensional MEC model approximates the complex three-dimensional flux paths of the TFM and includes the effects of magnetic saturation. The model is capable of adapting to any geometry that makes it a good alternative for evaluating prospective designs of TFM compared to finite element solvers that are numerically intensive and require more computation time. A single-phase, 1-kW, 400-rpm machine is analytically modeled, and its resulting flux distribution, no-load EMF, and torque are verified with finite element analysis. The results are found to be in agreement, with less than 5% error, while reducing the computation time by 25 times.

  7. The Impact of Prior Biosphere Models in the Inversion of Global Terrestrial CO2 Fluxes by Assimilating OCO-2 Retrievals

    Science.gov (United States)

    Philip, Sajeev; Johnson, Matthew S.

    2018-01-01

    Atmospheric mixing ratios of carbon dioxide (CO2) are largely controlled by anthropogenic emissions and biospheric fluxes. The processes controlling terrestrial biosphere-atmosphere carbon exchange are currently not fully understood, resulting in terrestrial biospheric models having significant differences in the quantification of biospheric CO2 fluxes. Atmospheric transport models assimilating measured (in situ or space-borne) CO2 concentrations to estimate "top-down" fluxes, generally use these biospheric CO2 fluxes as a priori information. Most of the flux inversion estimates result in substantially different spatio-temporal posteriori estimates of regional and global biospheric CO2 fluxes. The Orbiting Carbon Observatory 2 (OCO-2) satellite mission dedicated to accurately measure column CO2 (XCO2) allows for an improved understanding of global biospheric CO2 fluxes. OCO-2 provides much-needed CO2 observations in data-limited regions facilitating better global and regional estimates of "top-down" CO2 fluxes through inversion model simulations. The specific objectives of our research are to: 1) conduct GEOS-Chem 4D-Var assimilation of OCO-2 observations, using several state-of-the-science biospheric CO2 flux models as a priori information, to better constrain terrestrial CO2 fluxes, and 2) quantify the impact of different biospheric model prior fluxes on OCO-2-assimilated a posteriori CO2 flux estimates. Here we present our assessment of the importance of these a priori fluxes by conducting Observing System Simulation Experiments (OSSE) using simulated OCO-2 observations with known "true" fluxes.

  8. Assessing the Importance of Prior Biospheric Fluxes on Inverse Model Estimates of CO2

    Science.gov (United States)

    Philip, S.; Johnson, M. S.; Potter, C. S.; Genovese, V. B.

    2017-12-01

    Atmospheric mixing ratios of carbon dioxide (CO2) are largely controlled by anthropogenic emissions and biospheric sources/sinks. The processes controlling terrestrial biosphere-atmosphere carbon exchange are currently not fully understood, resulting in models having significant differences in the quantification of biospheric CO2 fluxes. Currently, atmospheric chemical transport models (CTM) and global climate models (GCM) use multiple different biospheric CO2 flux models resulting in large differences in simulating the global carbon cycle. The Orbiting Carbon Observatory 2 (OCO-2) satellite mission was designed to allow for the improved understanding of the processes involved in the exchange of carbon between terrestrial ecosystems and the atmosphere, and therefore allowing for more accurate assessment of the seasonal/inter-annual variability of CO2. OCO-2 provides much-needed CO2 observations in data-limited regions allowing for the evaluation of model simulations of greenhouse gases (GHG) and facilitating global/regional estimates of "top-down" CO2 fluxes. We conduct a 4-D Variation (4D-Var) data assimilation with the GEOS-Chem (Goddard Earth Observation System-Chemistry) CTM using 1) OCO-2 land nadir and land glint retrievals and 2) global in situ surface flask observations to constrain biospheric CO2 fluxes. We apply different state-of-the-science year-specific CO2 flux models (e.g., NASA-CASA (NASA-Carnegie Ames Stanford Approach), CASA-GFED (Global Fire Emissions Database), Simple Biosphere Model version 4 (SiB-4), and LPJ (Lund-Postdam-Jena)) to assess the impact of "a priori" flux predictions to "a posteriori" estimates. We will present the "top-down" CO2 flux estimates for the year 2015 using OCO-2 and in situ observations, and a complete indirect evaluation of the a priori and a posteriori flux estimates using independent in situ observations. We will also present our assessment of the variability of "top-down" CO2 flux estimates when using different

  9. Modeling metabolism and stage-specific growth of Plasmodium falciparum HB3 during the intraerythrocytic developmental cycle.

    Science.gov (United States)

    Fang, Xin; Reifman, Jaques; Wallqvist, Anders

    2014-10-01

    The human malaria parasite Plasmodium falciparum goes through a complex life cycle, including a roughly 48-hour-long intraerythrocytic developmental cycle (IDC) in human red blood cells. A better understanding of the metabolic processes required during the asexual blood-stage reproduction will enhance our basic knowledge of P. falciparum and help identify critical metabolic reactions and pathways associated with blood-stage malaria. We developed a metabolic network model that mechanistically links time-dependent gene expression, metabolism, and stage-specific growth, allowing us to predict the metabolic fluxes, the biomass production rates, and the timing of production of the different biomass components during the IDC. We predicted time- and stage-specific production of precursors and macromolecules for P. falciparum (strain HB3), allowing us to link specific metabolites to specific physiological functions. For example, we hypothesized that coenzyme A might be involved in late-IDC DNA replication and cell division. Moreover, the predicted ATP metabolism indicated that energy was mainly produced from glycolysis and utilized for non-metabolic processes. Finally, we used the model to classify the entire tricarboxylic acid cycle into segments, each with a distinct function, such as superoxide detoxification, glutamate/glutamine processing, and metabolism of fumarate as a byproduct of purine biosynthesis. By capturing the normal metabolic and growth progression in P. falciparum during the IDC, our model provides a starting point for further elucidation of strain-specific metabolic activity, host-parasite interactions, stress-induced metabolic responses, and metabolic responses to antimalarial drugs and drug candidates.

  10. New paradigms for metabolic modeling of human cells

    DEFF Research Database (Denmark)

    Mardinoglu, Adil; Nielsen, Jens

    2015-01-01

    review recent work on reconstruction of GEMs for human cell/tissue types and cancer, and the use of GEMs for identification of metabolic changes occurring in response to disease development. We further discuss how GEMs can be used for the development of efficient therapeutic strategies. Finally......, challenges in integration of cell/tissue models for simulation of whole body functions as well as integration of GEMs with other biological networks for generating complete cell/tissue models are presented.......Abnormalities in cellular functions are associated with the progression of human diseases, often resulting in metabolic reprogramming. GEnome-scale metabolic Models (GEMs) have enabled studying global metabolic reprogramming in connection with disease development in a systematic manner. Here we...

  11. A mathematical framework for yield (vs. rate) optimization in constraint-based modeling and applications in metabolic engineering.

    Science.gov (United States)

    Klamt, Steffen; Müller, Stefan; Regensburger, Georg; Zanghellini, Jürgen

    2018-02-07

    The optimization of metabolic rates (as linear objective functions) represents the methodical core of flux-balance analysis techniques which have become a standard tool for the study of genome-scale metabolic models. Besides (growth and synthesis) rates, metabolic yields are key parameters for the characterization of biochemical transformation processes, especially in the context of biotechnological applications. However, yields are ratios of rates, and hence the optimization of yields (as nonlinear objective functions) under arbitrary linear constraints is not possible with current flux-balance analysis techniques. Despite the fundamental importance of yields in constraint-based modeling, a comprehensive mathematical framework for yield optimization is still missing. We present a mathematical theory that allows one to systematically compute and analyze yield-optimal solutions of metabolic models under arbitrary linear constraints. In particular, we formulate yield optimization as a linear-fractional program. For practical computations, we transform the linear-fractional yield optimization problem to a (higher-dimensional) linear problem. Its solutions determine the solutions of the original problem and can be used to predict yield-optimal flux distributions in genome-scale metabolic models. For the theoretical analysis, we consider the linear-fractional problem directly. Most importantly, we show that the yield-optimal solution set (like the rate-optimal solution set) is determined by (yield-optimal) elementary flux vectors of the underlying metabolic model. However, yield- and rate-optimal solutions may differ from each other, and hence optimal (biomass or product) yields are not necessarily obtained at solutions with optimal (growth or synthesis) rates. Moreover, we discuss phase planes/production envelopes and yield spaces, in particular, we prove that yield spaces are convex and provide algorithms for their computation. We illustrate our findings by a small

  12. Effects of experimental nitrogen fertilization on planktonic metabolism and CO2 flux in a hypereutrophic hardwater lake.

    Directory of Open Access Journals (Sweden)

    Matthew J Bogard

    Full Text Available Hardwater lakes are common in human-dominated regions of the world and often experience pollution due to agricultural and urban effluent inputs of inorganic and organic nitrogen (N. Although these lakes are landscape hotspots for CO2 exchange and food web carbon (C cycling, the effect of N enrichment on hardwater lake food web functioning and C cycling patterns remains unclear. Specifically, it is unknown if different eutrophication scenarios (e.g., modest non point vs. extreme point sources yield consistent effects on auto- and heterotrophic C cycling, or how biotic responses interact with the inorganic C system to shape responses of air-water CO2 exchange. To address this uncertainty, we induced large metabolic gradients in the plankton community of a hypereutrophic hardwater Canadian prairie lake by adding N as urea (the most widely applied agricultural fertilizer at loading rates of 0, 1, 3, 8 or 18 mg N L-1 week-1 to 3240-L, in-situ mesocosms. Over three separate 21-day experiments, all treatments of N dramatically increased phytoplankton biomass and gross primary production (GPP two- to six-fold, but the effects of N on autotrophs plateaued at ~3 mg N L-1. Conversely, heterotrophic metabolism increased linearly with N fertilization over the full treatment range. In nearly all cases, N enhanced net planktonic uptake of dissolved inorganic carbon (DIC, and increased the rate of CO2 influx, while planktonic heterotrophy and CO2 production only occurred in the highest N treatments late in each experiment, and even in these cases, enclosures continued to in-gas CO2. Chemical effects on CO2 through calcite precipitation were also observed, but similarly did not change the direction of net CO2 flux. Taken together, these results demonstrate that atmospheric exchange of CO2 in eutrophic hardwater lakes remains sensitive to increasing N loading and eutrophication, and that even modest levels of N pollution are capable of enhancing autotrophy and CO

  13. Extension of virtual flux decomposition model to the case of two vegetation layers: FDM-2

    International Nuclear Information System (INIS)

    Kallel, Abdelaziz

    2012-01-01

    As an approximation, the forest could be assumed a discrete media composed of three main components: trees, understory vegetation and soil background. To describe the reflectance of such a canopy in the optical wavelength domain, it is necessary to develop a radiative transfer model which considers two vegetation layers (understory and trees). In this article, we propose a new model, FDM-2, an extension of the flux decomposition model (FDM), to take into account such a canopy architecture. Like FDM, FDM-2 models the diffuse flux anisotropy and takes into account the hot spot effect as well as conserves energy. The hot spot which corresponds to an increase of the probability of photon escape after first collision close to the backscattering direction is modeled as a decrease of “the effective vegetation density” encountered by the diffuse flux (E + 1 ) and the radiance both created by first order scattering of the direct sun radiation. Compared to the turbid case (for which our model is equivalent to SAIL++ and therefore accurately conserving energy), such a density variation redistributes energy but does not affect the budget. Energy remains well conserved in the discrete case as well. To solve the RT problem, FDM-2 separates E + 1 from the high order diffuse flux. As E + 1 corresponding effective density is not constant function of the altitude (when traveling along the canopy) therefore it is decomposed into sub-fluxes of constant densities. The sub-flux RT problems are linear and simply solved based on SAIL++ formalism. The global RT solution is obtained summing the contribution of the sub-fluxes. Simulation tests confirm that FDM-2 conserves energy (i.e., radiative budget closes to zero in the purist corner case with an error due to the discretization less than 0.5%). Compared to the Rayspread model (among the best 3-D models of the RAMI Exercise third phase), our model provides similar performance.

  14. Developing a forecast model of solar proton flux profiles for well-connected events

    Science.gov (United States)

    Ji, E. Y.; Moon, Y. J.; Park, J.

    2014-12-01

    We have developed a forecast model of solar proton flux profile (> 10 MeV channel) for well-connected events. Among 136 solar proton events (SPEs) from 1986 to 2006, we select 49 well-connected ones that are all associated with single X-ray flares stronger than M1 class and start to increase within four hours after their X-ray peak times. These events show rapid increments in proton flux. By comparing several empirical functions, we select a modified Weibull curve function to approximate a SPE flux profile, which is similar to the particle injection rate. The parameters (peak value, rise time and decay time) of this function are determined by the relationship between X-ray flare parameters (peak flux, impulsive time, and emission measure) and SPE parameters. For 49 well-connected SPEs, the linear correlation between the predicted proton peak flux and the observed proton peak fluxes is 0.65 with the RMS error of 0.55 pfu in the log10. In addition, we have developed another forecast model based on flare and CME parameters using 22 SPEs. The used CME parameters are linear speed and angular width. As a result, we find that the linear correlation between the predicted proton peak flux and the observed proton peak fluxes is 0.83 with the RMS error of 0.35 pfu in the log10. From the relationship between the model error and CME acceleration, we find that CME acceleration is also an important factor for predicting proton flux profiles.

  15. Pollutant Flux Estimation in an Estuary Comparison between Model and Field Measurements

    Directory of Open Access Journals (Sweden)

    Yen-Chang Chen

    2014-08-01

    Full Text Available This study proposes a framework for estimating pollutant flux in an estuary. An efficient method is applied to estimate the flux of pollutants in an estuary. A gauging station network in the Danshui River estuary is established to measure the data of water quality and discharge based on the efficient method. A boat mounted with an acoustic Doppler profiler (ADP traverses the river along a preselected path that is normal to the streamflow to measure the velocities, water depths and water quality for calculating pollutant flux. To know the characteristics of the estuary and to provide the basis for the pollutant flux estimation model, data of complete tidal cycles is collected. The discharge estimation model applies the maximum velocity and water level to estimate mean velocity and cross-sectional area, respectively. Thus, the pollutant flux of the estuary can be easily computed as the product of the mean velocity, cross-sectional area and pollutant concentration. The good agreement between the observed and estimated pollutant flux of the Danshui River estuary shows that the pollutant measured by the conventional and the efficient methods are not fundamentally different. The proposed method is cost-effective and reliable. It can be used to estimate pollutant flux in an estuary accurately and efficiently.

  16. ¹³C metabolic flux analysis identifies an unusual route for pyruvate dissimilation in mycobacteria which requires isocitrate lyase and carbon dioxide fixation.

    Directory of Open Access Journals (Sweden)

    Dany J V Beste

    2011-07-01

    Full Text Available Mycobacterium tuberculosis requires the enzyme isocitrate lyase (ICL for growth and virulence in vivo. The demonstration that M. tuberculosis also requires ICL for survival during nutrient starvation and has a role during steady state growth in a glycerol limited chemostat indicates a function for this enzyme which extends beyond fat metabolism. As isocitrate lyase is a potential drug target elucidating the role of this enzyme is of importance; however, the role of isocitrate lyase has never been investigated at the level of in vivo fluxes. Here we show that deletion of one of the two icl genes impairs the replication of Mycobacterium bovis BCG at slow growth rate in a carbon limited chemostat. In order to further understand the role of isocitrate lyase in the central metabolism of mycobacteria the effect of growth rate on the in vivo fluxes was studied for the first time using ¹³C-metabolic flux analysis (MFA. Tracer experiments were performed with steady state chemostat cultures of BCG or M. tuberculosis supplied with ¹³C labeled glycerol or sodium bicarbonate. Through measurements of the ¹³C isotopomer labeling patterns in protein-derived amino acids and enzymatic activity assays we have identified the activity of a novel pathway for pyruvate dissimilation. We named this the GAS pathway because it utilizes the Glyoxylate shunt and Anapleurotic reactions for oxidation of pyruvate, and Succinyl CoA synthetase for the generation of succinyl CoA combined with a very low flux through the succinate--oxaloacetate segment of the tricarboxylic acid cycle. We confirm that M. tuberculosis can fix carbon from CO₂ into biomass. As the human host is abundant in CO₂ this finding requires further investigation in vivo as CO₂ fixation may provide a point of vulnerability that could be targeted with novel drugs. This study also provides a platform for further studies into the metabolism of M. tuberculosis using ¹³C-MFA.

  17. Enhanced production of resveratrol derivatives in tobacco plants by improving the metabolic flux of intermediates in the phenylpropanoid pathway.

    Science.gov (United States)

    Jeong, Yu Jeong; An, Chul Han; Woo, Su Gyeong; Park, Ji Hye; Lee, Ki-Won; Lee, Sang-Hoon; Rim, Yeonggil; Jeong, Hyung Jae; Ryu, Young Bae; Kim, Cha Young

    2016-09-01

    The biosynthesis of flavonoids such as anthocyanin and stilbenes has attracted increasing attention because of their potential health benefits. Anthocyanins and stilbenes share common phenylpropanoid precursor pathways. We previously reported that the overexpression of sweetpotato IbMYB1a induced anthocyanin pigmentation in transgenic tobacco (Nicotiana tabacum) plants. In the present study, transgenic tobacco (Nicotiana tabacum SR1) plants (STS-OX and ROST-OX) expressing the RpSTS gene encoding stilbene synthase from rhubarb (Rheum palmatum L. cv. Jangyeop) and the RpSTS and VrROMT genes encoding resveratrol O-methyltransferase from frost grape (Vitis riparia) were generated under the control of 35S promoter. Phenotypic alterations in floral organs, such as a reduction in floral pigments and male sterility, were observed in STS-OX transgenic tobacco plants. However, we failed to obtain STS-OX and ROST-OX plants with high levels of resveratrol compounds. Therefore, to improve the production of resveratrol derivatives in plants, we cross-pollinated flowers of STS-OX or ROST-OX and IbMYB1a-OX transgenic lines (SM and RSM). Phenotypic changes in vegetative and reproductive development of SM and RSM plants were observed. Furthermore, by HPLC and LC-MS analyses, we found enhanced production of resveratrol derivatives such as piceid, piceid methyl ether, resveratrol methyl ether O-hexoside, and 5-methyl resveratrol-3,4'-O-β-D-diglucopyranoside in SM and RSM cross-pollinated lines. Here, total contents of trans- and cis-piceids ranged from approximately 104-240 µg/g fresh weight in SM (F2). Collectively, we suggest that coexpression of RpSTS and IbMYB1a via cross-pollination can induce enhanced production of resveratrol compounds in plants by increasing metabolic flux into stilbenoid biosynthesis.

  18. Effects of ocean acidification and hydrodynamic conditions on carbon metabolism and dissolved organic carbon (DOC) fluxes in seagrass populations.

    Science.gov (United States)

    Egea, Luis G; Jiménez-Ramos, Rocío; Hernández, Ignacio; Bouma, Tjeerd J; Brun, Fernando G

    2018-01-01

    Global change has been acknowledged as one of the main threats to the biosphere and its provision of ecosystem services, especially in marine ecosystems. Seagrasses play a critical ecological role in coastal ecosystems, but their responses to ocean acidification (OA) and climate change are not well understood. There have been previous studies focused on the effects of OA, but the outcome of interactions with co-factors predicted to alter during climate change still needs to be addressed. For example, the impact of higher CO2 and different hydrodynamic regimes on seagrass performance remains unknown. We studied the effects of OA under different current velocities on productivity of the seagrass Zostera noltei, using changes in dissolved oxygen as a proxy for the seagrass carbon metabolism, and release of dissolved organic carbon (DOC) in a four-week experiment using an open-water outdoor mesocosm. Under current pH conditions, increasing current velocity had a positive effect on productivity, but this depended on shoot density. However, this positive effect of current velocity disappeared under OA conditions. OA conditions led to a significant increase in gross production rate and respiration, suggesting that Z. noltei is carbon-limited under the current inorganic carbon concentration of seawater. In addition, an increase in non-structural carbohydrates was found, which may lead to better growing conditions and higher resilience in seagrasses subjected to environmental stress. Regarding DOC flux, a direct and positive relationship was found between current velocity and DOC release, both under current pH and OA conditions. We conclude that OA and high current velocity may lead to favourable growth scenarios for Z. noltei populations, increasing their productivity, non-structural carbohydrate concentrations and DOC release. Our results add new dimensions to predictions on how seagrass ecosystems will respond to climate change, with important implications for the

  19. Effects of ocean acidification and hydrodynamic conditions on carbon metabolism and dissolved organic carbon (DOC fluxes in seagrass populations.

    Directory of Open Access Journals (Sweden)

    Luis G Egea

    Full Text Available Global change has been acknowledged as one of the main threats to the biosphere and its provision of ecosystem services, especially in marine ecosystems. Seagrasses play a critical ecological role in coastal ecosystems, but their responses to ocean acidification (OA and climate change are not well understood. There have been previous studies focused on the effects of OA, but the outcome of interactions with co-factors predicted to alter during climate change still needs to be addressed. For example, the impact of higher CO2 and different hydrodynamic regimes on seagrass performance remains unknown. We studied the effects of OA under different current velocities on productivity of the seagrass Zostera noltei, using changes in dissolved oxygen as a proxy for the seagrass carbon metabolism, and release of dissolved organic carbon (DOC in a four-week experiment using an open-water outdoor mesocosm. Under current pH conditions, increasing current velocity had a positive effect on productivity, but this depended on shoot density. However, this positive effect of current velocity disappeared under OA conditions. OA conditions led to a significant increase in gross production rate and respiration, suggesting that Z. noltei is carbon-limited under the current inorganic carbon concentration of seawater. In addition, an increase in non-structural carbohydrates was found, which may lead to better growing conditions and higher resilience in seagrasses subjected to environmental stress. Regarding DOC flux, a direct and positive relationship was found between current velocity and DOC release, both under current pH and OA conditions. We conclude that OA and high current velocity may lead to favourable growth scenarios for Z. noltei populations, increasing their productivity, non-structural carbohydrate concentrations and DOC release. Our results add new dimensions to predictions on how seagrass ecosystems will respond to climate change, with important

  20. Reconciling surface ocean productivity, export fluxes and sediment composition in a global biogeochemical ocean model

    Directory of Open Access Journals (Sweden)

    M. Gehlen

    2006-01-01

    Full Text Available This study focuses on an improved representation of the biological soft tissue pump in the global three-dimensional biogeochemical ocean model PISCES. We compare three parameterizations of particle dynamics: (1 the model standard version including two particle size classes, aggregation-disaggregation and prescribed sinking speed; (2 an aggregation-disaggregation model with a particle size spectrum and prognostic sinking speed; (3 a mineral ballast parameterization with no size classes, but prognostic sinking speed. In addition, the model includes a description of surface sediments and organic carbon early diagenesis. Model output is compared to data or data based estimates of ocean productivity, pe-ratios, particle fluxes, surface sediment bulk composition and benthic O2 fluxes. Model results suggest that different processes control POC fluxes at different depths. In the wind mixed layer turbulent particle coagulation appears as key process in controlling pe-ratios. Parameterization (2 yields simulated pe-ratios that compare well to observations. Below the wind mixed layer, POC fluxes are most sensitive to the intensity of zooplankton flux feeding, indicating the importance of zooplankton community composition. All model parameters being kept constant, the capability of the model to reproduce yearly mean POC fluxes below 2000 m and benthic oxygen demand does at first order not dependent on the resolution of the particle size spectrum. Aggregate formation appears essential to initiate an intense biological pump. At great depth the reported close to constant particle fluxes are most likely the result of the combined effect of aggregate formation and mineral ballasting.

  1. Regional-scale geostatistical inverse modeling of North American CO2 fluxes: a synthetic data study

    Directory of Open Access Journals (Sweden)

    A. M. Michalak

    2010-07-01

    Full Text Available A series of synthetic data experiments is performed to investigate the ability of a regional atmospheric inversion to estimate grid-scale CO2 fluxes during the growing season over North America. The inversions are performed within a geostatistical framework without the use of any prior flux estimates or auxiliary variables, in order to focus on the atmospheric constraint provided by the nine towers collecting continuous, calibrated CO2 measurements in 2004. Using synthetic measurements and their associated concentration footprints, flux and model-data mismatch covariance parameters are first optimized, and then fluxes and their uncertainties are estimated at three different temporal resolutions. These temporal resolutions, which include a four-day average, a four-day-average diurnal cycle with 3-hourly increments, and 3-hourly fluxes, are chosen to help assess the impact of temporal aggregation errors on the estimated fluxes and covariance parameters. Estimating fluxes at a temporal resolution that can adjust the diurnal variability is found to be critical both for recovering covariance parameters directly from the atmospheric data, and for inferring accurate ecoregion-scale fluxes. Accounting for both spatial and temporal a priori covariance in the flux distribution is also found to be necessary for recovering accurate a posteriori uncertainty bounds on the estimated fluxes. Overall, the results suggest that even a fairly sparse network of 9 towers collecting continuous CO2 measurements across the continent, used with no auxiliary information or prior estimates of the flux distribution in time or space, can be used to infer relatively accurate monthly ecoregion scale CO2 surface fluxes over North America within estimated uncertainty bounds. Simulated random transport error is shown to decrease the quality of flux estimates in under-constrained areas at the ecoregion scale, although the uncertainty bounds remain realistic. While these synthetic

  2. Improvement of low energy atmospheric neutrino flux calculation using the JAM nuclear interaction model

    International Nuclear Information System (INIS)

    Honda, M.; Kajita, T.; Kasahara, K.; Midorikawa, S.

    2011-01-01

    We present the calculation of the atmospheric neutrino fluxes with an interaction model named JAM, which is used in PHITS (Particle and Heavy-Ion Transport code System) [K. Niita et al., Radiation Measurements 41, 1080 (2006).]. The JAM interaction model agrees with the HARP experiment [H. Collaboration, Astropart. Phys. 30, 124 (2008).] a little better than DPMJET-III[S. Roesler, R. Engel, and J. Ranft, arXiv:hep-ph/0012252.]. After some modifications, it reproduces the muon flux below 1 GeV/c at balloon altitudes better than the modified DPMJET-III, which we used for the calculation of atmospheric neutrino flux in previous works [T. Sanuki, M. Honda, T. Kajita, K. Kasahara, and S. Midorikawa, Phys. Rev. D 75, 043005 (2007).][M. Honda, T. Kajita, K. Kasahara, S. Midorikawa, and T. Sanuki, Phys. Rev. D 75, 043006 (2007).]. Some improvements in the calculation of atmospheric neutrino flux are also reported.

  3. An improved lattice hydrodynamic model considering the influence of optimal flux for forward looking sites

    Science.gov (United States)

    Wang, Yunong; Ge, Hongxia; Cheng, Rongjun

    2017-11-01

    In this paper, a lattice hydrodynamic model is derived considering the delayed-feedback control influence of optimal flux for forward looking sites on a single-lane road which includes more comprehensive information. The control method is used to analyze the stability of the model. The critical condition for the linear steady traffic flow is deduced and the numerical simulation is carried out to investigate the advantage of the proposed model with and without the effect of optimal flux for forward looking sites. Moreover it indicates that the characteristic of the model can lead to a lower energy consumption in traffic system. The results are consistent with the theoretical analysis correspondingly.

  4. Evapotranspiration and heat fluxes over a small forest - a study using modelling and measurements

    DEFF Research Database (Denmark)

    Sogachev, Andrey; Dellwik, Ebba; Boegh, Eva

    2013-01-01

    are very often used for calibration of forest parameters or model constants, further use of these parameters without a proper interpretation in mesoscale or global circulation models can result in serious bias of estimates of modelled evapotranspiration or heat fluxes from the given area. In the present...... work, we apply the atmospheric boundary layer (ABL) model SCADIS with enhanced turbulence closure including buoyancy for investigation of the spatial distribution of latent and sensible heat vertical fluxes over patchy forested terrain in Denmark during selected days in the summer period. The approach...

  5. Metabolic network model guided engineering ethylmalonyl-CoA pathway to improve ascomycin production in Streptomyces hygroscopicus var. ascomyceticus.

    Science.gov (United States)

    Wang, Junhua; Wang, Cheng; Song, Kejing; Wen, Jianping

    2017-10-03

    Ascomycin is a 23-membered polyketide macrolide with high immunosuppressant and antifungal activity. As the lower production in bio-fermentation, global metabolic analysis is required to further explore its biosynthetic network and determine the key limiting steps for rationally engineering. To achieve this goal, an engineering approach guided by a metabolic network model was implemented to better understand ascomycin biosynthesis and improve its production. The metabolic conservation of Streptomyces species was first investigated by comparing the metabolic enzymes of Streptomyces coelicolor A3(2) with those of 31 Streptomyces strains, the results showed that more than 72% of the examined proteins had high sequence similarity with counterparts in every surveyed strain. And it was found that metabolic reactions are more highly conserved than the enzymes themselves because of its lower diversity of metabolic functions than that of genes. The main source of the observed metabolic differences was from the diversity of secondary metabolism. According to the high conservation of primary metabolic reactions in Streptomyces species, the metabolic network model of Streptomyces hygroscopicus var. ascomyceticus was constructed based on the latest reported metabolic model of S. coelicolor A3(2) and validated experimentally. By coupling with flux balance analysis and using minimization of metabolic adjustment algorithm, potential targets for ascomycin overproduction were predicted. Since several of the preferred targets were highly associated with ethylmalonyl-CoA biosynthesis, two target genes hcd (encoding 3-hydroxybutyryl-CoA dehydrogenase) and ccr (encoding crotonyl-CoA carboxylase/reductase) were selected for overexpression in S. hygroscopicus var. ascomyceticus FS35. Both the mutants HA-Hcd and HA-Ccr showed higher ascomycin titer, which was consistent with the model predictions. Furthermore, the combined effects of the two genes were evaluated and the strain HA

  6. Genome-scale metabolic models applied to human health and disease.

    Science.gov (United States)

    Cook, Daniel J; Nielsen, Jens

    2017-11-01

    Advances in genome sequencing, high throughput measurement of gene and protein expression levels, data accessibility, and computational power have allowed genome-scale metabolic models (GEMs) to become a useful tool for understanding metabolic alterations associated with many different diseases. Despite the proven utility of GEMs, researchers confront multiple challenges in the use of GEMs, their application to human health and disease, and their construction and simulation in an organ-specific and disease-specific manner. Several approaches that researchers are taking to address these challenges include using proteomic and transcriptomic-informed methods to build GEMs for individual organs, diseases, and patients and using constraints on model behavior during simulation to match observed metabolic fluxes. We review the challenges facing researchers in the use of GEMs, review the approaches used to address these challenges, and describe advances that are on the horizon and could lead to a better understanding of human metabolism. WIREs Syst Biol Med 2017, 9:e1393. doi: 10.1002/wsbm.1393 For further resources related to this article, please visit the WIREs website. © 2017 Wiley Periodicals, Inc.

  7. Development of permeate flux model for municipal wastewater treatment using membrane bioreactor

    International Nuclear Information System (INIS)

    Geissler, S.; Zhou, H.; Zytner, R.; Melin, T.

    2002-01-01

    In municipal wastewater treatment, membrane filtration technologies receive great attention because they usually produce the better quality effluent, generate less sludge and require a smaller aeration tank volume. However, one main challenge of using membranes is membrane fouling, which results in a permeate flux decrease or transmembrane pressure increase over the time. Many efforts have been directed to develop the mechanistic permeate flux model to correlate the permeate flux with process parameters. However, their applicability has been largely thwarted due to complicated membrane fouling mechanisms and the interactions of many factors affecting the membrane bioreactor. This paper proposes a semi-empirical permeate flux model for the membrane bioreactor (MBR) process using ZENON immersed hollow fibre membrane modules. The semi-empirical model was proposed by assuming that the permeate flux is equal to transmembrane pressure divided by total resistance. The total resistance is divided into two components: an inside membrane resistance and an outer fouling layer resistance. These membrane resistances are then related to the ageing of membrane used. Good correlation was found between the predicted and measured flux, with the mean absolute deviation being less than 4%. The observations also identified some general rules for operating membrane systems. Ideally, it is advisable that high pressure periods be avoided as this leads to a faster increase of non-reversal membrane resistance. It was also observed that membrane preservatives should be washed out carefully prior to use. (author)

  8. Study of cosmic ray interaction model based on atmospheric muons for the neutrino flux calculation

    International Nuclear Information System (INIS)

    Sanuki, T.; Honda, M.; Kajita, T.; Kasahara, K.; Midorikawa, S.

    2007-01-01

    We have studied the hadronic interaction for the calculation of the atmospheric neutrino flux by summarizing the accurately measured atmospheric muon flux data and comparing with simulations. We find the atmospheric muon and neutrino fluxes respond to errors in the π-production of the hadronic interaction similarly, and compare the atmospheric muon flux calculated using the HKKM04 [M. Honda, T. Kajita, K. Kasahara, and S. Midorikawa, Phys. Rev. D 70, 043008 (2004).] code with experimental measurements. The μ + +μ - data show good agreement in the 1∼30 GeV/c range, but a large disagreement above 30 GeV/c. The μ + /μ - ratio shows sizable differences at lower and higher momenta for opposite directions. As the disagreements are considered to be due to assumptions in the hadronic interaction model, we try to improve it phenomenologically based on the quark parton model. The improved interaction model reproduces the observed muon flux data well. The calculation of the atmospheric neutrino flux will be reported in the following paper [M. Honda et al., Phys. Rev. D 75, 043006 (2007).

  9. Statistical modelling of variability in sediment-water nutrient and oxygen fluxes

    Science.gov (United States)

    Serpetti, Natalia; Witte, Ursula; Heath, Michael

    2016-06-01

    Organic detritus entering, or produced, in the marine environment is re-mineralised to inorganic nutrient in the seafloor sediments. The flux of dissolved inorganic nutrient between the sediment and overlying water column is a key process in the marine ecosystem, which binds the biogeochemical sub-system to the living food web. These fluxes are potentially affected by a wide range of physical and biological factors and disentangling these is a significant challenge. Here we develop a set of General Additive Models (GAM) of nitrate, nitrite, ammonia, phosphate, silicate and oxygen fluxes, based on a year-long campaign of field measurements off the north-east coast of Scotland. We show that sediment grain size, turbidity due to sediment re-suspension, temperature, and biogenic matter content were the key factors affecting oxygen consumption, ammonia and silicate fluxes. However, phosphate fluxes were only related to suspended sediment concentrations, whilst nitrate fluxes showed no clear relationship to any of the expected drivers of change, probably due to the effects of denitrification. Our analyses show that the stoichiometry of nutrient regeneration in the ecosystem is not necessarily constant and may be affected by combinations of processes. We anticipate that our statistical modelling results will form the basis for testing the functionality of process-based mathematical models of whole-sediment biogeochemistry.

  10. Measurements and modeling of gas fluxes in unsaturated mine waste materials

    Energy Technology Data Exchange (ETDEWEB)

    Kabwe, L.K.

    2008-07-01

    A technique known as dynamic closed chamber (DDC) was recently developed to measure carbon dioxide (CO{sub 2}) fluxes from the soil surface to the atmosphere. The field application of the DCC was investigated in this thesis with a particular focus on quantifying reaction rates in 2 waste-rock piles at the Key Lake uranium mine in northern Saskatchewan. The dominant geochemical reactions in both waste-rock piles were not typical of acid rock drainage (ARD) waste-rock piles. The CO{sub 2} fluxes measured in this study occur in the organic material underlying the waste rocks. The study provided a complete suite of measurements needed to characterize spatial distribution of CO{sub 2} fluxes on larger-scale studies of waste-rock piles. In comparison to other CO{sub 2} flux measuring techniques, the DCC method accurately quantified field soil respiration and had an added advantage in terms of speed and repeatability. The DCC was also used to investigate CO{sub 2} fluxes under the climatic variables that affect soil water content in waste-rock piles. A simple model for predicting the effects of soil water content on CO{sub 2} diffusion coefficient and concentration profiles was developed and verified. It was concluded that the DCC method is suitable for field applications to quantify CO{sub 2} fluxes and to characterize the spatial and temporal dynamics of CO{sub 2} fluxes from unsaturated C-horizon soils and waste-rock piles.

  11. Flux and anisotropy of galactic cosmic rays: beyond homogeneous models

    International Nuclear Information System (INIS)

    Bernard, Guilhem

    2013-01-01

    In this thesis I study the consequence of non homogeneously distributed cosmic ray sources in the Milky way. The document starts with theoretical and experimental synthesis. Firstly, I will describe the interstellar medium to understand the mechanism of propagation and acceleration of cosmic rays. Then, the detailed study of cosmic rays diffusion on the galactic magnetic field allows to write a commonly used propagation equation. I will recall the Steady-state solutions of this equation, then I will focus on the time dependant solutions with point-like sources. A statistical study is performed in order to estimate the standard deviation of the flux around its mean value. The computation of this standard deviation leads to mathematical divergences. Thus, I will develop statistical tools to bypass this issue. So i will discuss the effect of the granularity of cosmic ray sources. Its impact on cosmic ray spectrum can explain some recent features observed by the experiments CREAM and PAMELA.Besides, this thesis is focused on the study of the anisotropy of cosmic rays. I will recap experimental methods of measurements, and I will show how to connect theoretical calculation from propagation theories to experimental measurements. Then, the influence of the local environment on the anisotropy measurements will be discussed, particularly the effect of a local diffusion coefficient. Then, I will compute anisotropy and its variance in a framework of point-like local sources with the tools developed in the first part. Finally, the possible influence of local sources on the anisotropy is discussed in the light of the last experimental results. (author) [fr

  12. Gyrokinetic modelling of the quasilinear particle flux for plasmas with neutral-beam fuelling

    Science.gov (United States)

    Narita, E.; Honda, M.; Nakata, M.; Yoshida, M.; Takenaga, H.; Hayashi, N.

    2018-02-01

    A quasilinear particle flux is modelled based on gyrokinetic calculations. The particle flux is estimated by determining factors, namely, coefficients of off-diagonal terms and a particle diffusivity. In this paper, the methodology to estimate the factors is presented using a subset of JT-60U plasmas. First, the coefficients of off-diagonal terms are estimated by linear gyrokinetic calculations. Next, to obtain the particle diffusivity, a semi-empirical approach is taken. Most experimental analyses for particle transport have assumed that turbulent particle fluxes are zero in the core region. On the other hand, even in the stationary state, the plasmas in question have a finite turbulent particle flux due to neutral-beam fuelling. By combining estimates of the experimental turbulent particle flux and the coefficients of off-diagonal terms calculated earlier, the particle diffusivity is obtained. The particle diffusivity should reflect a saturation amplitude of instabilities. The particle diffusivity is investigated in terms of the effects of the linear instability and linear zonal flow response, and it is found that a formula including these effects roughly reproduces the particle diffusivity. The developed framework for prediction of the particle flux is flexible to add terms neglected in the current model. The methodology to estimate the quasilinear particle flux requires so low computational cost that a database consisting of the resultant coefficients of off-diagonal terms and particle diffusivity can be constructed to train a neural network. The development of the methodology is the first step towards a neural-network-based particle transport model for fast prediction of the particle flux.

  13. Carbon Dioxide Transfer Through Sea Ice: Modelling Flux in Brine Channels

    Science.gov (United States)

    Edwards, L.; Mitchelson-Jacob, G.; Hardman-Mountford, N.

    2010-12-01

    For many years sea ice was thought to act as a barrier to the flux of CO2 between the ocean and atmosphere. However, laboratory-based and in-situ observations suggest that while sea ice may in some circumstances reduce or prevent transfer (e.g. in regions of thick, superimposed multi-year ice), it may also be highly permeable (e.g. thin, first year ice) with some studies observing significant fluxes of CO2. Sea ice covered regions have been observed to act both as a sink and a source of atmospheric CO2 with the permeability of sea ice and direction of flux related to sea ice temperature and the presence of brine channels in the ice, as well as seasonal processes such as whether the ice is freezing or thawing. Brine channels concentrate dissolved inorganic carbon (DIC) as well as salinity and as these dense waters descend through both the sea ice and the surface ocean waters, they create a sink for CO2. Calcium carbonate (ikaite) precipitation in the sea ice is thought to enhance this process. Micro-organisms present within the sea ice will also contribute to the CO2 flux dynamics. Recent evidence of decreasing sea ice extent and the associated change from a multi-year ice to first-year ice dominated system suggest the potential for increased CO2 flux through regions of thinner, more porous sea ice. A full understanding of the processes and feedbacks controlling the flux in these regions is needed to determine their possible contribution to global CO2 levels in a future warming climate scenario. Despite the significance of these regions, the air-sea CO2 flux in sea ice covered regions is not currently included in global climate models. Incorporating this carbon flux system into Earth System models requires the development of a well-parameterised sea ice-air flux model. In our work we use the Los Alamos sea ice model, CICE, with a modification to incorporate the movement of CO2 through brine channels including the addition of DIC processes and ice algae production to

  14. Dynamic plant uptake modelling and mass flux estimation

    DEFF Research Database (Denmark)

    Rein, Arno; Bauer-Gottwein, Peter; Trapp, Stefan

    2011-01-01

    in environmental systems at different scales. Feedback mechanisms between plants and hydrological systems can play an important role. However, they have received little attention to date. Here, a new model concept for dynamic plant uptake models applying analytical matrix solutions is presented, which can...

  15. Monitoring the latent and sensible heat fluxes in vineyard by applying the energy balance model METRIC

    Directory of Open Access Journals (Sweden)

    J. González-Piqueras

    2015-06-01

    Full Text Available The monitoring of the energy fluxes over vineyard applying the one source energy balance model METRIC (Allen et al., 2007b are shown in this work. This model is considered operaive because it uses an internalized calibration method derived from the selection of two extreme pixels in the scene, from the minimum ET values such as the bare soil to a maximum that corresponds to full cover active vegetation. The model provides the maps of net radiation (Rn, soil heat flux (G, sensible heat (H, latent heat (LE, evapotranspiration (ET and crop coefficient (Kc. The flux values have been validated with a flux tower installed in the plot, providing a RMSE for instantaneous fluxes of 43 W m2, 33 W m2, 55 W m2 y 40 W m2 on Rn, G, H and LE. In relative terms are 8%, 29%, 21% and 20% respectively. The RMSE at daily scale for the ET is 0.58 mm day-1, with a value in the crop coefficient for the mid stage of 0.42±0.08. These results allow considering the model adequate for crop monitoring and irrigation purposes in vineyard. The values obtained have been compared to other studies over vineyard and with alternative energy balance models showing similar results.

  16. Applicability of TASS/SMR using drift flux model for SMART LOCA analysis

    Energy Technology Data Exchange (ETDEWEB)

    Chung, Young-Jong, E-mail: chung@kaeri.re.kr; Kim, Soo Hyung; Lee, Gyu Hyeung; Lee, Won Jae

    2013-09-15

    Highlights: • SMART plant and TASS/SMR code have been developed by KAERI. • TASS/SMR code adopts a drift flux model to consider relative velocity under two-phase condition. • Drift flux model in TASS/SMR is validated using separate effect test results. • Applicability of TASS/SMR using drift flux model for SMART LOCA analysis is confirmed. -- Abstract: Small reactors can apply to local power demands or remote areas. SMART, which can produce 90 MWe of electricity and 40,000 tons/day of sea-water desalination for a 100,000 population city, is a promising advanced integral type small reactor. The thermal hydraulic analysis code with a drift flux model, TASS/SMR, was developed for a conservative simulation of a small break loss of coolant accident in SMART. Taking into account SMART-specific inherent characteristics, the code adopts the Chexal–Lellouche correlation for a drift flux model. The capability of TASS/SMR code is validated using the results of the experimental data. The code predicts conservatively the void distribution compared with the experimental data. TASS/SMR calculation predicts reasonably major phenomena for the SBLOCA and is more conservative than or nearly the same as the results of the best estimated realistic system code, MARS. TASS/SMR code can be used for a SBLOCA analysis of SMART.

  17. Applicability of TASS/SMR using drift flux model for SMART LOCA analysis

    International Nuclear Information System (INIS)

    Chung, Young-Jong; Kim, Soo Hyung; Lee, Gyu Hyeung; Lee, Won Jae

    2013-01-01

    Highlights: • SMART plant and TASS/SMR code have been developed by KAERI. • TASS/SMR code adopts a drift flux model to consider relative velocity under two-phase condition. • Drift flux model in TASS/SMR is validated using separate effect test results. • Applicability of TASS/SMR using drift flux model for SMART LOCA analysis is confirmed. -- Abstract: Small reactors can apply to local power demands or remote areas. SMART, which can produce 90 MWe of electricity and 40,000 tons/day of sea-water desalination for a 100,000 population city, is a promising advanced integral type small reactor. The thermal hydraulic analysis code with a drift flux model, TASS/SMR, was developed for a conservative simulation of a small break loss of coolant accident in SMART. Taking into account SMART-specific inherent characteristics, the code adopts the Chexal–Lellouche correlation for a drift flux model. The capability of TASS/SMR code is validated using the results of the experimental data. The code predicts conservatively the void distribution compared with the experimental data. TASS/SMR calculation predicts reasonably major phenomena for the SBLOCA and is more conservative than or nearly the same as the results of the best estimated realistic system code, MARS. TASS/SMR code can be used for a SBLOCA analysis of SMART

  18. The effect of the advanced drift-flux model of ASSERT-PV on critical heat flux, flow and void distributions in CANDU bundle subchannels

    International Nuclear Information System (INIS)

    Hammouda, N.; Rao, Y.F.

    2017-01-01

    Highlights: • Presentation of the “advanced” drift-flux model of the subchannel code ASSERT-PV. • Study the effect of the drift-flux model of ASSERT on CHF and flow distribution. • Quantify model component effects with flow, quality and dryout power measurements. - Abstract: This paper studies the effect of the drift flux model of the subchannel code ASSERT-PV on critical heat flux (CHF), void fraction and flow distribution across fuel bundles. Numerical experiments and comparison against measurements were performed to examine the trends and relative behaviour of the different components of the model under various flow conditions. The drift flux model of ASSERT-PV is composed of three components: (a) the lateral component or diversion cross-flow, caused by pressure difference between connected subchannels, (b) the turbulent diffusion component or the turbulent mixing through gaps of subchannels, caused by instantaneous turbulent fluctuations or flow oscillations, and (c) the void drift component that occurs due to the two-phase tendency toward a preferred distribution. This study shows that the drift flux model has a significant impact on CHF, void fraction and flow distribution predictions. The lateral component of the drift flux model has a stronger effect on CHF predictions than the axial component, especially for horizontal flow. Predictions of CHF, void fraction and flow distributions are most sensitive to the turbulent diffusion component of the model, followed by the void drift component. Buoyancy drift can be significant, but it does not have as much influence on CHF and flow distribution as the turbulent diffusion and void drift.

  19. Derivation of a well-posed and multidimensional drift-flux model for boiling flows

    International Nuclear Information System (INIS)

    Gregoire, O.; Martin, M.

    2005-01-01

    In this note, we derive a multidimensional drift-flux model for boiling flows. Within this framework, the distribution parameter is no longer a scalar but a tensor that might account for the medium anisotropy and the flow regime. A new model for the drift-velocity vector is also derived. It intrinsically takes into account the effect of the friction pressure loss on the buoyancy force. On the other hand, we show that most drift-flux models might exhibit a singularity for large void fraction. In order to avoid this singularity, a remedy based on a simplified three field approach is proposed. (authors)

  20. A Computational Model of Water Migration Flux in Freezing Soil in a Closed System

    Institute of Scientific and Technical Information of China (English)

    裘春晗

    2005-01-01

    A computational model of water migration flux of fine porous soil in frost heave was investigated in a closed system. The model was established with the heat-mass conservation law and from some previous experimental results. Through defining an auxiliary function an empirical function in the water migration flux, which is difficult to get, was replaced. The data needed are about the water content along the soft colunm after test with enough long time. We adopt the test data of sample soil colunms in [1] to verify the model. The result shows it can reflect the real situation on the whole.

  1. Metabolic Modeling of Common Escherichia coli Strains in Human Gut Microbiome

    Directory of Open Access Journals (Sweden)

    Yue-Dong Gao

    2014-01-01

    Full Text Available The recent high-throughput sequencing has enabled the composition of Escherichia coli strains in the human microbial community to be profiled en masse. However, there are two challenges to address: (1 exploring the genetic differences between E. coli strains in human gut and (2 dynamic responses of E. coli to diverse stress conditions. As a result, we investigated the E. coli strains in human gut microbiome using deep sequencing data and reconstructed genome-wide metabolic networks for the three most common E. coli strains, including E. coli HS, UTI89, and CFT073. The metabolic models show obvious strain-specific characteristics, both in network contents and in behaviors. We predicted optimal biomass production for three models on four different carbon sources (acetate, ethanol, glucose, and succinate and found that these stress-associated genes were involved in host-microbial interactions and increased in human obesity. Besides, it shows that the growth rates are similar among the models, but the flux distributions are different, even in E. coli core reactions. The correlations between human diabetes-associated metabolic reactions in the E. coli models were also predicted. The study provides a systems perspective on E. coli strains in human gut microbiome and will be helpful in integrating diverse data sources in the following study.

  2. User-Friendly Predictive Modeling of Greenhouse Gas (GHG) Fluxes and Carbon Storage in Tidal Wetlands

    Science.gov (United States)

    Ishtiaq, K. S.; Abdul-Aziz, O. I.

    2015-12-01

    We developed user-friendly empirical models to predict instantaneous fluxes of CO2 and CH4 from coastal wetlands based on a small set of dominant hydro-climatic and environmental drivers (e.g., photosynthetically active radiation, soil temperature, water depth, and soil salinity). The dominant predictor variables were systematically identified by applying a robust data-analytics framework on a wide range of possible environmental variables driving wetland greenhouse gas (GHG) fluxes. The method comprised of a multi-layered data-analytics framework, including Pearson correlation analysis, explanatory principal component and factor analyses, and partial least squares regression modeling. The identified dominant predictors were finally utilized to develop power-law based non-linear regression models to predict CO2 and CH4 fluxes under different climatic, land use (nitrogen gradient), tidal hydrology and salinity conditions. Four different tidal wetlands of Waquoit Bay, MA were considered as the case study sites to identify the dominant drivers and evaluate model performance. The study sites were dominated by native Spartina Alterniflora and characterized by frequent flooding and high saline conditions. The model estimated the potential net ecosystem carbon balance (NECB) both in gC/m2 and metric tonC/hectare by up-scaling the instantaneous predicted fluxes to the growing season and accounting for the lateral C flux exchanges between the wetlands and estuary. The entire model was presented in a single Excel spreadsheet as a user-friendly ecological engineering tool. The model can aid the development of appropriate GHG offset protocols for setting monitoring plans for tidal wetland restoration and maintenance projects. The model can also be used to estimate wetland GHG fluxes and potential carbon storage under various IPCC climate change and sea level rise scenarios; facilitating an appropriate management of carbon stocks in tidal wetlands and their incorporation into a

  3. Multi-model analysis of terrestrial carbon cycles in Japan: limitations and implications of model calibration using eddy flux observations

    Directory of Open Access Journals (Sweden)

    K. Ichii

    2010-07-01

    Full Text Available Terrestrial biosphere models show large differences when simulating carbon and water cycles, and reducing these differences is a priority for developing more accurate estimates of the condition of terrestrial ecosystems and future climate change. To reduce uncertainties and improve the understanding of their carbon budgets, we investigated the utility of the eddy flux datasets to improve model simulations and reduce variabilities among multi-model outputs of terrestrial biosphere models in Japan. Using 9 terrestrial biosphere models (Support Vector Machine – based regressions, TOPS, CASA, VISIT, Biome-BGC, DAYCENT, SEIB, LPJ, and TRIFFID, we conducted two simulations: (1 point simulations at four eddy flux sites in Japan and (2 spatial simulations for Japan with a default model (based on original settings and a modified model (based on model parameter tuning using eddy flux data. Generally, models using default model settings showed large deviations in model outputs from observation with large model-by-model variability. However, after we calibrated the model parameters using eddy flux data (GPP, RE and NEP, most models successfully simulated seasonal variations in the carbon cycle, with less variability among models. We also found that interannual variations in the carbon cycle are mostly consistent among models and observations. Spatial analysis also showed a large reduction in the variability among model outputs. This study demonstrated that careful validation and calibration of models with available eddy flux data reduced model-by-model differences. Yet, site history, analysis of model structure changes, and more objective procedure of model calibration should be included in the further analysis.

  4. Multi-model analysis of terrestrial carbon cycles in Japan: limitations and implications of model calibration using eddy flux observations

    Science.gov (United States)

    Ichii, K.; Suzuki, T.; Kato, T.; Ito, A.; Hajima, T.; Ueyama, M.; Sasai, T.; Hirata, R.; Saigusa, N.; Ohtani, Y.; Takagi, K.

    2010-07-01

    Terrestrial biosphere models show large differences when simulating carbon and water cycles, and reducing these differences is a priority for developing more accurate estimates of the condition of terrestrial ecosystems and future climate change. To reduce uncertainties and improve the understanding of their carbon budgets, we investigated the utility of the eddy flux datasets to improve model simulations and reduce variabilities among multi-model outputs of terrestrial biosphere models in Japan. Using 9 terrestrial biosphere models (Support Vector Machine - based regressions, TOPS, CASA, VISIT, Biome-BGC, DAYCENT, SEIB, LPJ, and TRIFFID), we conducted two simulations: (1) point simulations at four eddy flux sites in Japan and (2) spatial simulations for Japan with a default model (based on original settings) and a modified model (based on model parameter tuning using eddy flux data). Generally, models using default model settings showed large deviations in model outputs from observation with large model-by-model variability. However, after we calibrated the model parameters using eddy flux data (GPP, RE and NEP), most models successfully simulated seasonal variations in the carbon cycle, with less variability among models. We also found that interannual variations in the carbon cycle are mostly consistent among models and observations. Spatial analysis also showed a large reduction in the variability among model outputs. This study demonstrated that careful validation and calibration of models with available eddy flux data reduced model-by-model differences. Yet, site history, analysis of model structure changes, and more objective procedure of model calibration should be included in the further analysis.

  5. Osteoarthritis and metabolic dysregulation: insights from a preclinical model

    NARCIS (Netherlands)

    Visser, H.M. de

    2018-01-01

    This thesis aims to identify the effect of metabolic factors, inflammatory processes and obesity in the pathophysiology of osteoarthritis (OA), using a high-fat diet and/or traumatic injury in a small animal model. The first part of this thesis describes, the rat Groove model of OA, using a one-time

  6. Modeling metabolic response to changes of enzyme amount in ...

    African Journals Online (AJOL)

    Based on the work of Hynne et al. (2001), in an in silico model of glycolysis, Saccharomyces cerevisiae is established by introducing an enzyme amount multiple factor (.) into the kinetic equations. The model is aimed to predict the metabolic response to the change of enzyme amount. With the help of .α, the amounts of ...

  7. Dynamic optimal metabolic control theory: a cybernetic approach for modelling of the central nitrogen metabolism of S. cerevisiae

    NARCIS (Netherlands)

    Riel, van N.A.W.; Giuseppin, M.L.F.; Verrips, C.T.

    2000-01-01

    The theory of dynamic optimal metabolic control (DOMC), as developed by Giuseppin and Van Riel (Metab. Eng., 2000), is applied to model the central nitrogen metabolism (CNM) in Saccharomyces cerevisiae. The CNM represents a typical system encountered in advanced metabolic engineering. The CNM is the

  8. Flux coupling and transcriptional regulation within the metabolic network of the photosynthetic bacterium Synechocystis sp. PCC6803

    DEFF Research Database (Denmark)

    Montagud, Arnau; Zelezniak, Aleksej; Navarro, Emilio

    2011-01-01

    networks, surrounded by a stable core of pathways leading to biomass building blocks. This analysis identified potential bottlenecks for hydrogen and ethanol production. Integration of transcriptomic data with the Synechocystis flux coupling networks lead to identification of reporter flux coupling pairs...

  9. Metabolism

    Science.gov (United States)

    ... Are More Common in People With Type 1 Diabetes Metabolic Syndrome Your Child's Weight Healthy Eating Endocrine System Blood Test: Basic Metabolic Panel (BMP) Activity: Endocrine System Growth Disorders Diabetes Center Thyroid Disorders Your Endocrine System Movie: Endocrine ...

  10. Bioenergetics-based modeling of Plasmodium falciparum metabolism reveals its essential genes, nutritional requirements, and thermodynamic bottlenecks

    Science.gov (United States)

    Chiappino-Pepe, Anush; Ataman, Meriç

    2017-01-01

    Novel antimalarial therapies are urgently needed for the fight against drug-resistant parasites. The metabolism of malaria parasites in infected cells is an attractive source of drug targets but is rather complex. Computational methods can handle this complexity and allow integrative analyses of cell metabolism. In this study, we present a genome-scale metabolic model (iPfa) of the deadliest malaria parasite, Plasmodium falciparum, and its thermodynamics-based flux analysis (TFA). Using previous absolute concentration data of the intraerythrocytic parasite, we applied TFA to iPfa and predicted up to 63 essential genes and 26 essential pairs of genes. Of the 63 genes, 35 have been experimentally validated and reported in the literature, and 28 have not been experimentally tested and include previously hypothesized or novel predictions of essential metabolic capabilities. Without metabolomics data, four of the genes would have been incorrectly predicted to be non-essential. TFA also indicated that substrate channeling should exist in two metabolic pathways to ensure the thermodynamic feasibility of the flux. Finally, analysis of the metabolic capabilities of P. falciparum led to the identification of both the minimal nutritional requirements and the genes that can become indispensable upon substrate inaccessibility. This model provides novel insight into the metabolic needs and capabilities of the malaria parasite and highlights metabolites and pathways that should be measured and characterized to identify potential thermodynamic bottlenecks and substrate channeling. The hypotheses presented seek to guide experimental studies to facilitate a better understanding of the parasite metabolism and the identification of targets for more efficient intervention. PMID:28333921

  11. Bioenergetics-based modeling of Plasmodium falciparum metabolism reveals its essential genes, nutritional requirements, and thermodynamic bottlenecks.

    Directory of Open Access Journals (Sweden)

    Anush Chiappino-Pepe

    2017-03-01

    Full Text Available Novel antimalarial therapies are urgently needed for the fight against drug-resistant parasites. The metabolism of malaria parasites in infected cells is an attractive source of drug targets but is rather complex. Computational methods can handle this complexity and allow integrative analyses of cell metabolism. In this study, we present a genome-scale metabolic model (iPfa of the deadliest malaria parasite, Plasmodium falciparum, and its thermodynamics-based flux analysis (TFA. Using previous absolute concentration data of the intraerythrocytic parasite, we applied TFA to iPfa and predicted up to 63 essential genes and 26 essential pairs of genes. Of the 63 genes, 35 have been experimentally validated and reported in the literature, and 28 have not been experimentally tested and include previously hypothesized or novel predictions of essential metabolic capabilities. Without metabolomics data, four of the genes would have been incorrectly predicted to be non-essential. TFA also indicated that substrate channeling should exist in two metabolic pathways to ensure the thermodynamic feasibility of the flux. Finally, analysis of the metabolic capabilities of P. falciparum led to the identification of both the minimal nutritional requirements and the genes that can become indispensable upon substrate inaccessibility. This model provides novel insight into the metabolic needs and capabilities of the malaria parasite and highlights metabolites and pathways that should be measured and characterized to identify potential thermodynamic bottlenecks and substrate channeling. The hypotheses presented seek to guide experimental studies to facilitate a better understanding of the parasite metabolism and the identification of targets for more efficient intervention.

  12. Models of Eucalypt phenology predict bat population flux.

    Science.gov (United States)

    Giles, John R; Plowright, Raina K; Eby, Peggy; Peel, Alison J; McCallum, Hamish

    2016-10-01

    Fruit bats (Pteropodidae) have received increased attention after the recent emergence of notable viral pathogens of bat origin. Their vagility hinders data collection on abundance and distribution, which constrains modeling efforts and our understanding of bat ecology, viral dynamics, and spillover. We addressed this knowledge gap with models and data on the occurrence and abundance of nectarivorous fruit bat populations at 3 day roosts in southeast Queensland. We used environmental drivers of nectar production as predictors and explored relationships between bat abundance and virus spillover. Specifically, we developed several novel modeling tools motivated by complexities of fruit bat foraging ecology, including: (1) a dataset of spatial variables comprising Eucalypt-focused vegetation indices, cumulative precipitation, and temperature anomaly; (2) an algorithm that associated bat population response with spatial covariates in a spatially and temporally relevant way given our current understanding of bat foraging behavior; and (3) a thorough statistical learning approach to finding optimal covariate combinations. We identified covariates that classify fruit bat occupancy at each of our three study roosts with 86-93% accuracy. Negative binomial models explained 43-53% of the variation in observed abundance across roosts. Our models suggest that spatiotemporal heterogeneity in Eucalypt-based food resources could drive at least 50% of bat population behavior at the landscape scale. We found that 13 spillover events were observed within the foraging range of our study roosts, and they occurred during times when models predicted low population abundance. Our results suggest that, in southeast Queensland, spillover may not be driven by large aggregations of fruit bats attracted by nectar-based resources, but rather by behavior of smaller resident subpopulations. Our models and data integrated remote sensing and statistical learning to make inferences on bat ecology

  13. Two-field and drift-flux models with application to nuclear reactor safety

    International Nuclear Information System (INIS)

    Travis, J.R.

    1986-01-01

    The ideas of the two-field (6 equation model) and drift-flux (4 equation model) description of two-phase flows are presented. Several example calculations relating to reactor safety are discussed and comparisons of the numerical results and experimental data are shown to be in good agreement. 16 refs., 32 figs

  14. Ozone flux of an urban orange grove: multiple scaled measurements and model comparisons

    Science.gov (United States)

    Alstad, K. P.; Grulke, N. E.; Jenerette, D. G.; Schilling, S.; Marrett, K.

    2009-12-01

    There is significant uncertainty about the ozone sink properties of the phytosphere due to a complexity of interactions and feedbacks with biotic and abiotic factors. Improved understanding of the controls on ozone fluxes is critical to estimating and regulating the total ozone budget. Ozone exchanges of an orange orchard within the city of Riverside, CA were examined using a multiple-scaled approach. We access the carbon, water, and energy budgets at the stand- to leaf- level to elucidate the mechanisms controlling the variability in ozone fluxes of this agro-ecosystem. The two initial goals of the study were 1. To consider variations and controls on the ozone fluxes within the canopy; and, 2. To examine different modeling and scaling approaches for totaling the ozone fluxes of this orchard. Current understanding of the total ozone flux between the atmosphere near ground and the phytosphere (F-total) include consideration of a fraction which is absorbed by vegetation through stomatal uptake (F-absorb), and fractional components of deposition on external, non-stomatal, surfaces of the vegetation (F-external) and soil (F-soil). Multiplicative stomatal-conductance models have been commonly used to estimate F-absorb, since this flux cannot be measured directly. We approach F-absorb estimates for this orange orchard using chamber measurement of leaf stomatal-conductance, as well as non-chamber sap-conductance collected on branches of varied aspect and sun/shade conditions within the canopy. We use two approaches to measure the F-total of this stand. Gradient flux profiles were measured using slow-response ozone sensors collecting within and above the canopy (4.6 m), and at the top of the tower (8.5 m). In addition, an eddy-covariance system fitted with a high-frequency chemiluminescence ozone system will be deployed (8.5 m). Preliminary ozone gradient flux profiles demonstrate a substantial ozone sink strength of this orchard, with diurnal concentration differentials

  15. Modelling magnetic laminations under arbitrary starting state and flux waveform

    International Nuclear Information System (INIS)

    Bottauscio, Oriano; Chiampi, Mario; Ragusa, Carlo

    2005-01-01

    A numerical model able to predict the behaviour of a magnetic sheet under arbitrary supply conditions has been developed. The electromagnetic field problem is formulated in terms of an electric vector potential, which provides the magnetic field strength evolution. The hysteretic behaviour of the material is represented through the dynamic Preisach model where the activation law of the bi-state operators is modified in order to guarantee a smooth response. The problem has been solved through a time step procedure using the fixed Point technique for handling nonlinearity. The model has been validated by comparison with suitable experiments and it is applied to the investigation of the influence of the materials' starting state on the magnetic behaviour

  16. Dynamical fragmentation of flux tubes in the Friedberg-Lee model

    International Nuclear Information System (INIS)

    Loh, S.; Greiner, C.; Mosel, U.; Thoma, M.H.

    1997-01-01

    We present two novel dynamical features of flux tubes in the Friedberg-Lee model. First the fusion of two (anti-)parallel flux tubes, where we extract a string-string interaction potential which has a qualitative similarity to the nucleon-nucleon potential in the Friedberg-Lee model obtained by Koepf et al. Furthermore we show the dynamical breakup of flux tubes via qq-particle production and the disintegration into mesons. We find, as a shortcoming of the present realization of the model, that the full dynamical transport approach presented in a previous publication fails to provide the disintegration mechanism in the semiclassical limit. Therefore, in addition, we present here a molecular dynamical approach for the motion of the quarks and show, as a first application, the space-time development of the quarks and their mean-fields for Lund-type string fragmentation processes. (orig.)

  17. Fluxes of biogenic volatile organic compounds measured and modelled above a Norway spruce forest

    Science.gov (United States)

    Juráň, Stanislav; Fares, Silvano; Pallozzi, Emanuele; Guidolotti, Gabriele; Savi, Flavia; Alivernini, Alessandro; Calfapietra, Carlo; Večeřová, Kristýna; Křůmal, Kamil; Večeřa, Zbyněk; Cudlín, Pavel; Urban, Otmar

    2016-04-01

    Fluxes of biogenic volatile organic compounds (BVOCs) were investigated at Norway spruce forest at Bílý Kříž in Beskydy Mountains of the Czech Republic during the summer 2014. A proton-transfer-reaction-time-of-flight mass spectrometer (PTR-TOF-MS, Ionicon Analytik, Austria) has been coupled with eddy-covariance system. Additionally, Inverse Lagrangian Transport Model has been used to derive fluxes from concentration gradient of various monoterpenes previously absorbed into n-heptane by wet effluent diffusion denuder with consequent quantification by gas chromatography with mass spectrometry detection. Modelled data cover each one day of three years with different climatic conditions and previous precipitation patterns. Model MEGAN was run to cover all dataset with monoterpene fluxes and measured basal emission factor. Highest fluxes measured by eddy-covariance were recorded during the noon hours, represented particularly by monoterpenes and isoprene. Inverse Lagrangian Transport Model suggests most abundant monoterpene fluxes being α- and β-pinene. Principal component analysis revealed dependencies of individual monoterpene fluxes on air temperature and particularly global radiation; however, these dependencies were monoterpene specific. Relationships of monoterpene fluxes with CO2 flux and relative air humidity were found to be negative. MEGAN model correlated to eddy-covariance PTR-TOF-MS measurement evince particular differences, which will be shown and discussed. Bi-directional fluxes of oxygenated short-chain volatiles (methanol, formaldehyde, acetone, acetaldehyde, formic acid, acetic acid, methyl vinyl ketone, methacrolein, and methyl ethyl ketone) were recorded by PTR-TOF-MS. Volatiles of anthropogenic origin as benzene and toluene were likely transported from the most benzene polluted region in Europe - Ostrava city and adjacent part of Poland around Katowice, where metallurgical and coal mining industries are located. Those were accumulated during

  18. Evaluation of a Genome-Scale In Silico Metabolic Model for Geobacter metallireducens by Using Proteomic Data from a Field Biostimulation Experiment

    Science.gov (United States)

    Fang, Yilin; Yabusaki, Steven B.; Lipton, Mary S.; Long, Philip E.

    2012-01-01

    Accurately predicting the interactions between microbial metabolism and the physical subsurface environment is necessary to enhance subsurface energy development, soil and groundwater cleanup, and carbon management. This study was an initial attempt to confirm the metabolic functional roles within an in silico model using environmental proteomic data collected during field experiments. Shotgun global proteomics data collected during a subsurface biostimulation experiment were used to validate a genome-scale metabolic model of Geobacter metallireducens—specifically, the ability of the metabolic model to predict metal reduction, biomass yield, and growth rate under dynamic field conditions. The constraint-based in silico model of G. metallireducens relates an annotated genome sequence to the physiological functions with 697 reactions controlled by 747 enzyme-coding genes. Proteomic analysis showed that 180 of the 637 G. metallireducens proteins detected during the 2008 experiment were associated with specific metabolic reactions in the in silico model. When the field-calibrated Fe(III) terminal electron acceptor process reaction in a reactive transport model for the field experiments was replaced with the genome-scale model, the model predicted that the largest metabolic fluxes through the in silico model reactions generally correspond to the highest abundances of proteins that catalyze those reactions. Central metabolism predicted by the model agrees well with protein abundance profiles inferred from proteomic analysis. Model discrepancies with the proteomic data, such as the relatively low abundances of proteins associated with amino acid transport and metabolism, revealed pathways or flux constraints in the in silico model that could be updated to more accurately predict metabolic processes that occur in the subsurface environment. PMID:23042184

  19. Use of genome-scale microbial models for metabolic engineering

    DEFF Research Database (Denmark)

    Patil, Kiran Raosaheb; Åkesson, M.; Nielsen, Jens

    2004-01-01

    Metabolic engineering serves as an integrated approach to design new cell factories by providing rational design procedures and valuable mathematical and experimental tools. Mathematical models have an important role for phenotypic analysis, but can also be used for the design of optimal metaboli...... network structures. The major challenge for metabolic engineering in the post-genomic era is to broaden its design methodologies to incorporate genome-scale biological data. Genome-scale stoichiometric models of microorganisms represent a first step in this direction....

  20. Short-term impacts of enhanced Greenland freshwater fluxes in an eddy-permitting ocean model

    Directory of Open Access Journals (Sweden)

    R. Marsh

    2010-07-01

    Full Text Available In a sensitivity experiment, an eddy-permitting ocean general circulation model is forced with realistic freshwater fluxes from the Greenland Ice Sheet, averaged for the period 1991–2000. The fluxes are obtained with a mass balance model for the ice sheet, forced with the ERA-40 reanalysis dataset. The freshwater flux is distributed around Greenland as an additional term in prescribed runoff, representing seasonal melting of the ice sheet and a fixed year-round iceberg calving flux, for 8.5 model years. By adding Greenland freshwater fluxes with realistic geographical distribution and seasonality, the experiment is designed to investigate the oceanic response to a sudden and spatially/temporally uniform amplification of ice sheet melting and discharge, rather than localized or gradual changes in freshwater flux. The impacts on regional hydrography and circulation are investigated by comparing the sensitivity experiment to a control experiment, without additional fluxes. By the end of the sensitivity experiment, the majority of additional fresh water has accumulated in Baffin Bay, and only a small fraction has reached the interior of the Labrador Sea, where winter mixed layer depth is sensitive to small changes in salinity. As a consequence, the impact on large-scale circulation is very slight. An indirect impact of strong freshening off the west coast of Greenland is a small anti-cyclonic component to the circulation around Greenland, which opposes the wind-driven cyclonic circulation and reduces net southward flow through the Canadian Archipelago by ~10%. Implications for the post-2000 acceleration of Greenland mass loss are discussed.

  1. Metabolic alterations in experimental models of depression

    Directory of Open Access Journals (Sweden)

    Maria G. Puiu

    2016-10-01

    Full Text Available Introduction: Major depressive disorder is one of the most prevalent psychiatric disorders and is associated with a severe impact on the personal functioning, thus with incurring significant direct and indirect costs. The presence of depression in patients with medical comorbidities increases the risks of myocardial infarction and decreases diabetes control, and adherence to treatment. The mechanism through which these effects are produced is still uncertain. Objectives of this study were to evaluate the metabolic alterations in female Wistar rats with induced depression, with and without administration of Agomelatine. The methods included two experiments. All data were analyzed by comparison with group I (control, and with each other. In the first experiment we induced depression by: exposure to chronic mild stress-group II; olfactory bulbectomy-group III; and exposure to chronic mild stress and hyperlipidic/ hyper caloric dietgroup IV. The second experiment was similar with the first but the rats received Agomelatine (0.16mg/ animal: group V (depression induced through exposure to chronic mild stress, VI (depression induced through olfactory bulbectomy and VII (depression induced through exposure to chronic mild stressing hyperlipidic/ hypercaloric diet. Weight, cholesterol, triglycerides and glycaemia were measured at day 0 and 28, and leptin value was measured at day 28. The results in the 1st experiment revealed significant differences (p<0.01 for weight and cholesterol in Group IV, for triglycerides in groups III and IV (p<0.001, and for glycaemia in group II. The 2nd experiment revealed significant differences (p<0.001 in group VII for weight and triglycerides, and in groups V and VI for triglycerides (p<0.01. In conclusion, significant correlations were found between high level of triglycerides and depression induced by chronic stress and olfactory bulbectomy. Agomelatine groups had a lower increase of triglycerides levels.

  2. Genome-scale modelling of microbial metabolism with temporal and spatial resolution.

    Science.gov (United States)

    Henson, Michael A

    2015-12-01

    Most natural microbial systems have evolved to function in environments with temporal and spatial variations. A major limitation to understanding such complex systems is the lack of mathematical modelling frameworks that connect the genomes of individual species and temporal and spatial variations in the environment to system behaviour. The goal of this review is to introduce the emerging field of spatiotemporal metabolic modelling based on genome-scale reconstructions of microbial metabolism. The extension of flux balance analysis (FBA) to account for both temporal and spatial variations in the environment is termed spatiotemporal FBA (SFBA). Following a brief overview of FBA and its established dynamic extension, the SFBA problem is introduced and recent progress is described. Three case studies are reviewed to illustrate the current state-of-the-art and possible future research directions are outlined. The author posits that SFBA is the next frontier for microbial metabolic modelling and a rapid increase in methods development and system applications is anticipated. © 2015 Authors; published by Portland Press Limited.

  3. A genetic screen for increasing metabolic flux in the isoprenoid pathway of Saccharomyces cerevisiae: Isolation of SPT15 mutants using the screen

    Directory of Open Access Journals (Sweden)

    M. Wadhwa

    2016-12-01

    Full Text Available A genetic screen to identify mutants that can increase flux in the isoprenoid pathway of yeast has been lacking. We describe a carotenoid-based visual screen built with the core carotenogenic enzymes from the red yeast Rhodosporidium toruloides. Enzymes from this yeast displayed the required, higher capacity in the carotenoid pathway. The development also included the identification of the metabolic bottlenecks, primarily phytoene dehydrogenase, that was subjected to a directed evolution strategy to yield more active mutants. To further limit phytoene pools, a less efficient version of GGPP synthase was employed. The screen was validated with a known flux increasing gene, tHMG1. New mutants in the TATA binding protein SPT15 were isolated using this screen that increased the yield of carotenoids, and an alternate isoprenoid, α-Farnesene confirming increase in overall flux. The findings indicate the presence of previously unknown links to the isoprenoid pathway that can be uncovered using this screen. Keywords: Metabolic engineering, Carotenoids, Isoprenoids, α-Farnesene, Rhodosporidium toruloides, SPT15

  4. Verification of land-atmosphere coupling in forecast models, reanalyses and land surface models using flux site observations.

    Science.gov (United States)

    Dirmeyer, Paul A; Chen, Liang; Wu, Jiexia; Shin, Chul-Su; Huang, Bohua; Cash, Benjamin A; Bosilovich, Michael G; Mahanama, Sarith; Koster, Randal D; Santanello, Joseph A; Ek, Michael B; Balsamo, Gianpaolo; Dutra, Emanuel; Lawrence, D M

    2018-02-01

    We confront four model systems in three configurations (LSM, LSM+GCM, and reanalysis) with global flux tower observations to validate states, surface fluxes, and coupling indices between land and atmosphere. Models clearly under-represent the feedback of surface fluxes on boundary layer properties (the atmospheric leg of land-atmosphere coupling), and may over-represent the connection between soil moisture and surface fluxes (the terrestrial leg). Models generally under-represent spatial and temporal variability relative to observations, which is at least partially an artifact of the differences in spatial scale between model grid boxes and flux tower footprints. All models bias high in near-surface humidity and downward shortwave radiation, struggle to represent precipitation accurately, and show serious problems in reproducing surface albedos. These errors create challenges for models to partition surface energy properly and errors are traceable through the surface energy and water cycles. The spatial distribution of the amplitude and phase of annual cycles (first harmonic) are generally well reproduced, but the biases in means tend to reflect in these amplitudes. Interannual variability is also a challenge for models to reproduce. Our analysis illuminates targets for coupled land-atmosphere model development, as well as the value of long-term globally-distributed observational monitoring.

  5. Modeling nitrogen fluxes in Germany - where does the nitrogen go?

    Science.gov (United States)

    Klement, Laura; Bach, Martin; Breuer, Lutz

    2016-04-01

    According to the latest inventory of the EU Water Framework Directive, 26.3% of German groundwater bodies are in a poor chemical state regarding nitrate. Additionally, the EU initiated infringement proceedings against Germany for not meeting the quality standards of the EU Nitrate Directive. Agriculture has been determined as the main source of nitrate pollution due to over-fertilization and regionally high density of livestock farming. The nitrogen balance surplus is commonly used as an indicator characterizing the potential of nitrate leaching into groundwater bodies and thus also serves as a foundation to introduce legislative restrictions or to monitor the success of mitigation measures. Currently, there is an ongoing discussion which measures are suitable for reducing the risk of nitrate leaching and also to what extent. However, there is still uncertainty about just how much the nitrogen surplus has to be reduced to meet the groundwater quality standards nationwide. Therefore, the aims of our study were firstly to determine the level of the nitrogen surplus that would be acceptable at the utmost and secondly whether the currently discussed target value of 30 kg N per hectare agricultural land for the soil surface nitrogen balance would be sufficient. The models MONERIS (Modeling Nutrient Emissions in River System) and MoRE (Modelling of Regionalized Emissions), the latter based on the first, are commonly used for estimating nitrogen loads into the river system in Germany at the mesoscale, as well as the effect of mitigation measures in the context of the EU directive 2008/105/EC (Environmental quality standards applicable to surface water). We used MoRE to calculate nitrate concentration for 2759 analytical units in Germany. Main factors are the surplus of the soil surface nitrogen balance, the percolation rate and an exponent representing the denitrification in the vadose zone. The modeled groundwater nitrate concentrations did not correspond to the regional

  6. Modelling surface energy fluxes over a Dehesa ecosystem using a two-source energy balance model.

    Science.gov (United States)

    Andreu, Ana; Kustas, William. P.; Anderson, Martha C.; Carrara, Arnaud; Patrocinio Gonzalez-Dugo, Maria

    2013-04-01

    The Dehesa is the most widespread agroforestry land-use system in Europe, covering more than 3 million hectares in the Iberian Peninsula and Greece (Grove and Rackham, 2001; Papanastasis, 2004). It is an agro-silvo-pastural ecosystem consisting of widely-spaced oak trees (mostly Quercus ilex L.), combined with crops, pasture and Mediterranean shrubs, and it is recognized as an example of sustainable land use and for his importance in the rural economy (Diaz et al., 1997; Plieninger and Wilbrand, 2001). The ecosystem is influenced by a Mediterranean climate, with recurrent and severe droughts. Over the last decades the Dehesa has faced multiple environmental threats, derived from intensive agricultural use and socio-economic changes, which have caused environmental degradation of the area, namely reduction in tree density and stocking rates, changes in soil properties and hydrological processes and an increase of soil erosion (Coelho et al. 2004; Schnabel and Ferreira, 2004; Montoya 1998; Pulido and Díaz, 2005). Understanding the hydrological, atmospheric and physiological processes that affect the functioning of the ecosystem will improve the management and conservation of the Dehesa. One of the key metrics in assessing ecosystem health, particularly in this water-limited environment, is the capability of monitoring evaporation (ET). To make large area assessments requires the use of remote sensing. Thermal-based energy balance techniques that distinguish soil/substrate and vegetation contributions to the radiative temperature and radiation/turbulent fluxes have proven to be reliable in such semi-arid sparse canopy-cover landscapes. In particular, the two-source energy balance (TSEB) model of Norman et al. (1995) and Kustas and Norman (1999) has shown to be robust for a wide range of partially-vegetated landscapes. The TSEB formulation is evaluated at a flux tower site located in center Spain (Majadas del Tietar, Caceres). Its application in this environment is

  7. Source-Flux-Fate Modelling of Priority Pollutants in Stormwater Systems

    DEFF Research Database (Denmark)

    Vezzaro, Luca

    quality management. The thesis provides a framework for the trustworthy application of models to estimate PP fluxes from their sources, and through stormwater drainage systems, and to the sink. This fills a knowledge gap regarding stormwater PP and it supplies urban water managers with modelling tools......The increasing focus on management of stormwater Priority Pollutants (PP) enhances the role of mathematical models as support for the assessment of stormwater quality control strategies. This thesis investigates and presents modelling approaches that are suitable to simulate PP fluxes across...... stormwater systems, supporting the development of pollution control strategies. This is obtained by analyzing four study areas: (i) catchment characterization, (ii) pollutant release and transport models, (iii) stormwater treatment models, and (iv) combination of the above into an integrated model. Given...

  8. Study of the Relap5/mod3.2 wall heat flux partitioning model

    International Nuclear Information System (INIS)

    Hari, S.; Hassan, Y.A.

    2001-01-01

    The performance of the subcooled boiling model adapted in RELAP5/MOD3.2 computer code has been assessed in detail for low-pressure conditions and it has been found that the void fraction profile is under-predicted. In general, any subcooled boiling model is composed of individual sub-models that account for the different physical mechanism that govern the overall process, as the wall vapor generation, interfacial shear and condensation etc. The wall heat flux partitioning model is one of the important sub-models that is a constituent of any subcooled boiling model. The function of this model is to apportion the wall heat flux to the different components (as the single/two phase fluid or bubble), as the case may be, in a two-phase flow-boiling scenario adjacent to a heated wall. The ''pumping factor'' approach is generally followed by most of the wall heat flux partitioning models, for partitioning the wall heat flux. In this work, the wall heat flux partitioning model of RELAP5/MOD3.2 computer code is studied; in particular, the ''pumping factor'' formulation in the present code version is assessed for its performance under low-pressure conditions. In addition, three different ''pumping factor'' formulations available in the literature have been introduced into the RELAP5/MOD3.2 code. Simulations of two low-pressure subcooled flow boiling experiments were performed with the refined code versions to determine the appropriate pumping factor to be used under these conditions. (author)

  9. Modeling surface energy fluxes and thermal dynamics of a seasonally ice-covered hydroelectric reservoir.

    Science.gov (United States)

    Wang, Weifeng; Roulet, Nigel T; Strachan, Ian B; Tremblay, Alain

    2016-04-15

    The thermal dynamics of human created northern reservoirs (e.g., water temperatures and ice cover dynamics) influence carbon processing and air-water gas exchange. Here, we developed a process-based one-dimensional model (Snow, Ice, WAater, and Sediment: SIWAS) to simulate a full year's surface energy fluxes and thermal dynamics for a moderately large (>500km(2)) boreal hydroelectric reservoir in northern Quebec, Canada. There is a lack of climate and weather data for most of the Canadian boreal so we designed SIWAS with a minimum of inputs and with a daily time step. The modeled surface energy fluxes were consistent with six years of observations from eddy covariance measurements taken in the middle of the reservoir. The simulated water temperature profiles agreed well with observations from over 100 sites across the reservoir. The model successfully captured the observed annual trend of ice cover timing, although the model overestimated the length of ice cover period (15days). Sensitivity analysis revealed that air temperature significantly affects the ice cover duration, water and sediment temperatures, but that dissolved organic carbon concentrations have little effect on the heat fluxes, and water and sediment temperatures. We conclude that the SIWAS model is capable of simulating surface energy fluxes and thermal dynamics for boreal reservoirs in regions where high temporal resolution climate data are not available. SIWAS is suitable for integration into biogeochemical models for simulating a reservoir's carbon cycle. Copyright © 2016 Elsevier B.V. All rights reserved.

  10. Flux breaking of E6 in the generalised Hosotani model

    International Nuclear Information System (INIS)

    McLachlan, A.

    1989-01-01

    To break gauge symmetries in the Hosotani model, it is necessary to include periodic (Dirac) fermions and/or antiperiodic scalars which transform as single-valued faithful representations of the adjoint group. With this in mind, an E 6 Yang-Mills theory minimally coupled to periodic adjoint and antiperiodic fundamental fermions is examined. On breaking, even though the full rank six residual group depends on the numbers of spacetime dimensions and fermion families, the fundamental fermions surviving compactification only transform non-trivially under the omnipresent [SU(3)] 2 or SU(6) subgroup factors. (orig.)

  11. Evaluation of empirical heat transfer models using TFG heat flux sensors

    International Nuclear Information System (INIS)

    De Cuyper, T.; Broekaert, S.; Chana, K.; De Paepe, M.; Verhelst, S.

    2017-01-01

    Thermodynamic engine cycle models are used to support the development of the internal combustion engine (ICE) in a cost and time effective manner. The sub model which describes the in-cylinder heat transfer from the working gases to the combustion chamber walls plays an important role in the accuracy of these simulation tools. The heat transfer affects the power output, engine efficiency and emissions of the engine. The most common heat transfer models in engine research are the models of Annand and Woschni. These models provide an instantaneous spatial averaged heat flux. In this research, prototype thin film gauge (TFG) heat flux sensors are used to capture the transient in-cylinder heat flux behavior within a production spark ignition (SI) engine as they are small, robust and able to capture the highly transient temperature swings. An inlet valve and two different zones of the cylinder head are instrumented with multiple TFG sensors. The heat flux traces are used to calculate the convection coefficient which includes all information of the convective heat transfer phenomena inside the combustion chamber. The implementation of TFG sensors inside the combustion chamber and the signal processing technique are discussed. The heat transfer measurements are used to analyze the spatial variation in heat flux under motored and fired operation. Spatial variation in peak heat flux was observed even under motored operation. Under fired operation the observed spatial variation is mainly driven by the flame propagation. Next, the paper evaluates the models of Annand and Woschni. These models fail to predict the total heat loss even with calibration of the models coefficients using a reference motored operating condition. The effect of engine speed and inlet pressure is analyzed under motored operation after calibration of the models. The models are able to predict the trend in peak heat flux value for a varying engine speed and inlet pressure. Next, the accuracy of the

  12. Analyzing the causes and spatial pattern of the European 2003 carbon flux anomaly using seven models

    Directory of Open Access Journals (Sweden)

    M. Vetter

    2008-04-01

    Full Text Available Globally, the year 2003 is associated with one of the largest atmospheric CO2 rises on record. In the same year, Europe experienced an anomalously strong flux of CO2 from the land to the atmosphere associated with an exceptionally dry and hot summer in Western and Central Europe. In this study we analyze the magnitude of this carbon flux anomaly and key driving ecosystem processes using simulations of seven terrestrial ecosystem models of different complexity and types (process-oriented and diagnostic. We address the following questions: (1 how large were deviations in the net European carbon flux in 2003 relative to a short-term baseline (1998–2002 and to longer-term variations in annual fluxes (1980 to 2005, (2 which European regions exhibited the largest changes in carbon fluxes during the growing season 2003, and (3 which ecosystem processes controlled the carbon balance anomaly .

    In most models the prominence of 2003 anomaly in carbon fluxes declined with lengthening of the reference period from one year to 16 years. The 2003 anomaly for annual net carbon fluxes ranged between 0.35 and –0.63 Pg C for a reference period of one year and between 0.17 and –0.37 Pg C for a reference period of 16 years for the whole Europe.

    In Western and Central Europe, the anomaly in simulated net ecosystem productivity (NEP over the growing season in 2003 was outside the 1σ variance bound of the carbon flux anomalies for 1980–2005 in all models. The estimated anomaly in net carbon flux ranged between –42 and –158 Tg C for Western Europe and between 24 and –129 Tg C for Central Europe depending on the model used. All models responded to a dipole pattern of the climate anomaly in 2003. In Western and Central Europe NEP was reduced due to heat and drought. In contrast, lower than normal temperatures and higher air humidity decreased NEP over Northeastern Europe. While models agree on the sign of changes in

  13. Cardiovascular Changes in Animal Models of Metabolic Syndrome

    Directory of Open Access Journals (Sweden)

    Alexandre M. Lehnen

    2013-01-01

    Full Text Available Metabolic syndrome has been defined as a group of risk factors that directly contribute to the development of cardiovascular disease and/or type 2 diabetes. Insulin resistance seems to have a fundamental role in the genesis of this syndrome. Over the past years to the present day, basic and translational research has used small animal models to explore the pathophysiology of metabolic syndrome and to develop novel therapies that might slow the progression of this prevalent condition. In this paper we discuss the animal models used for the study of metabolic syndrome, with particular focus on cardiovascular changes, since they are the main cause of death associated with the condition in humans.

  14. Neutron activation analysis: Modelling studies to improve the neutron flux of Americium-Beryllium source

    Energy Technology Data Exchange (ETDEWEB)

    Didi, Abdessamad; Dadouch, Ahmed; Tajmouati, Jaouad; Bekkouri, Hassane [Advanced Technology and Integration System, Dept. of Physics, Faculty of Science Dhar Mehraz, University Sidi Mohamed Ben Abdellah, Fez (Morocco); Jai, Otman [Laboratory of Radiation and Nuclear Systems, Dept. of Physics, Faculty of Sciences, Tetouan (Morocco)

    2017-06-15

    Americium–beryllium (Am-Be; n, γ) is a neutron emitting source used in various research fields such as chemistry, physics, geology, archaeology, medicine, and environmental monitoring, as well as in the forensic sciences. It is a mobile source of neutron activity (20 Ci), yielding a small thermal neutron flux that is water moderated. The aim of this study is to develop a model to increase the neutron thermal flux of a source such as Am-Be. This study achieved multiple advantageous results: primarily, it will help us perform neutron activation analysis. Next, it will give us the opportunity to produce radio-elements with short half-lives. Am-Be single and multisource (5 sources) experiments were performed within an irradiation facility with a paraffin moderator. The resulting models mainly increase the thermal neutron flux compared to the traditional method with water moderator.

  15. Spatially Distributed, Coupled Modeling of Plant Growth, Nitrogen and Water Fluxes in an Alpine Catchment

    Science.gov (United States)

    Schneider, K.

    2001-12-01

    Carbon, water and nitrogen fluxes are closely coupled. They interact and have many feedbacks. Human interference, in particular through land use management and global change strongly modifies these fluxes. Increasing demands and conflicting interests result in an increasing need for regulation targeting different aspects of the system. Without being their main target, many of these measures directly affect water quantity, quality and availability. Improved management and planning of our water resources requires the development of integrated tools, in particular since interactions of the involved environmental and social systems often lead to unexpected or adverse results. To investigate the effect of plant growth, land use management and global change on water fluxes and quality, the PROcess oriented Modular EnvironmenT and Vegetation Model (PROMET-V) was developed. PROMET-V models the spatial patterns and temporal course of water, carbon and nitrogen fluxes using process oriented and mechanistic model components. The hydrological model is based on the Penman-Monteith approach, it uses a plant-physiological model to calculate the canopy conductance, and a multi-layer soil water model. Plant growth for different vegetation is modelled by calculating canopy photosynthesis, respiration, phenology and allocation. Plant growth and water fluxes are coupled directly through photosynthesis and transpiration. Many indirect feedbacks and interactions occur due to their mutual dependency upon leaf area, root distribution, water and nutrient availability for instance. PROMET-V calculates nitrogen fluxes and transformations. The time step used depends upon the modelled process and varies from 1 hour to 1 day. The kernel model is integrated in a raster GIS system for spatially distributed modelling. PROMET-V was tested in a pre-alpine landscape (Ammer river, 709 km**2, located in Southern Germany) which is characterized by small scale spatial heterogeneities of climate, soil and

  16. Uncertainty analysis of the Operational Simplified Surface Energy Balance (SSEBop) model at multiple flux tower sites

    Science.gov (United States)

    Chen, Mingshi; Senay, Gabriel B.; Singh, Ramesh K.; Verdin, James P.

    2016-01-01

    Evapotranspiration (ET) is an important component of the water cycle – ET from the land surface returns approximately 60% of the global precipitation back to the atmosphere. ET also plays an important role in energy transport among the biosphere, atmosphere, and hydrosphere. Current regional to global and daily to annual ET estimation relies mainly on surface energy balance (SEB) ET models or statistical and empirical methods driven by remote sensing data and various climatological databases. These models have uncertainties due to inevitable input errors, poorly defined parameters, and inadequate model structures. The eddy covariance measurements on water, energy, and carbon fluxes at the AmeriFlux tower sites provide an opportunity to assess the ET modeling uncertainties. In this study, we focused on uncertainty analysis of the Operational Simplified Surface Energy Balance (SSEBop) model for ET estimation at multiple AmeriFlux tower sites with diverse land cover characteristics and climatic conditions. The 8-day composite 1-km MODerate resolution Imaging Spectroradiometer (MODIS) land surface temperature (LST) was used as input land surface temperature for the SSEBop algorithms. The other input data were taken from the AmeriFlux database. Results of statistical analysis indicated that the SSEBop model performed well in estimating ET with an R2 of 0.86 between estimated ET and eddy covariance measurements at 42 AmeriFlux tower sites during 2001–2007. It was encouraging to see that the best performance was observed for croplands, where R2 was 0.92 with a root mean square error of 13 mm/month. The uncertainties or random errors from input variables and parameters of the SSEBop model led to monthly ET estimates with relative errors less than 20% across multiple flux tower sites distributed across different biomes. This uncertainty of the SSEBop model lies within the error range of other SEB models, suggesting systematic error or bias of the SSEBop model is within

  17. Modelling Particulate Removal in Tubular Wet Electrostatic Precipitators Using a Modified Drift Flux Model

    Directory of Open Access Journals (Sweden)

    S Ramechecandane

    2016-09-01

    Full Text Available Tubular electrostatic precipitators (ESP have been used in a number of chemical processing industries. The tubular ESPs have many advantages over conventional plate-plate and wire-plate ESPs. The present study is concerned with the numerical modeling of particulate removal in a tubular wet single-stage electrostatic precipitator (wESP. The geometric parameters of a model wESP and the corresponding inlet gas velocities for the wESP are chosen from available experimental data. In addition to the RNG k - ε model for the mean turbulent flow field inside the wESP, the Poisson equation for the electric field, the charge continuity equation and the concentration equation are solved sequentially to obtain a full-fledged solution to the problem under investigation. The proposed drift flux model is implemented in the opensource CFD code OpenFOAM®. The paper discusses the influence of the number of charges acquired by the particles and the corresponding inlet gas velocities on particle concentration distribution within the wESP. Two representative cases with monodispersed particles of 1 μm and 10 μm diameter are considered for the numerical analysis. It is seen from the present analysis that the number of units of charge on particles, the particle size and the inlet gas velocities play a vital role in determining the efficiency of electrostatic precipitation.

  18. Modelling atmospheric deposition flux of Cadmium and Lead in urban areas

    International Nuclear Information System (INIS)

    Cherin, Nicolas

    2017-01-01

    According to WHO, air pollution is responsible for more than 3.7 million premature deaths each year (OMS, 2014). Moreover, among these deaths, more than 70 within urban areas. Consequently, the health and environmental impacts of pollutants within these urban areas are of great concern in air quality studies. The deposition fluxes of air pollutants, which can be significant near sources of pollution, have rarely been modeled within urban areas. Historically, atmospheric deposition studies have focused mostly on remote areas to assess the potential impacts on ecosystems of acid deposition and nitrogen loading. Therefore, current atmospheric deposition models may not be suitable to simulate deposition fluxes in urban areas, which include complex surface geometries and diverse land use types. Atmospheric dry deposition is typically modeled using an average roughness length, which depends on land use. This classical roughness-length approach cannot account for the spatial variability of dry deposition in complex settings such as urban areas. Urban canopy models have been developed to parameterize momentum and heat transfer. We extend this approach here to mass transfer, and a new dry deposition model based on the urban canyon concept is presented. It uses a local mixing-length parameterization of turbulence within the canopy, and a description of the urban canopy via key parameters to provide spatially distributed dry deposition fluxes. This approach provides spatially distributed dry deposition fluxes depending on surfaces (streets, walls, roofs) and flow regimes (recirculation and ventilation) within the urban area. (author) [fr

  19. Implementation of drift-flux model in artist and assessment to thetis void distribution

    International Nuclear Information System (INIS)

    Kim, H. C.; Yun, B. J.; Moon, S. K.; Jeong, J. J.; Lee, W. J.

    1998-01-01

    A system transient analysis code, ARTIST, based on the drift-flux model is being developed to enhance capability of predicting two-phase flow void distribution at low pressure and low flow conditions. The governing equations of the ARTIST code consist of three continuity equations (mixture, liquid, and noncondensibles), two energy equations (gas and mixture) and one mixture momentum euqation constituted with the drift-flux model. Area averaged one-dimensional conservation equations are established using the flow quality expressed in terms of the relative velocity. The relative velocity is obtained from the drift flux relationship. The Chexal-Lellouche void fraction correlation is used to provide the drift velocity and the concentration parameter. The implicit one-step method and the block elimination technique are employed as numerical solution scheme for the node-flowpath thermal-hydraulic network. In order to validate the ARIST code, the steady state void distributions of the THETIS boil-off tests are simulated. The axial void distributions calculated by the Chexal-Lellouche fraction correlation at low pressure and low flow are better than those of both the two-fluid model of RELAP5/MOD3 code and the homogeneous model. The drift-flux model of the ARTIST code is an efficient tool in predicting the void distribution of two-phase flow at low pressure and low flow condtions

  20. An Analytical Diffusion–Expansion Model for Forbush Decreases Caused by Flux Ropes

    Science.gov (United States)

    Dumbović, Mateja; Heber, Bernd; Vršnak, Bojan; Temmer, Manuela; Kirin, Anamarija

    2018-06-01

    We present an analytical diffusion–expansion Forbush decrease (FD) model ForbMod, which is based on the widely used approach of an initially empty, closed magnetic structure (i.e., flux rope) that fills up slowly with particles by perpendicular diffusion. The model is restricted to explaining only the depression caused by the magnetic structure of the interplanetary coronal mass ejection (ICME). We use remote CME observations and a 3D reconstruction method (the graduated cylindrical shell method) to constrain initial boundary conditions of the FD model and take into account CME evolutionary properties by incorporating flux rope expansion. Several flux rope expansion modes are considered, which can lead to different FD characteristics. In general, the model is qualitatively in agreement with observations, whereas quantitative agreement depends on the diffusion coefficient and the expansion properties (interplay of the diffusion and expansion). A case study was performed to explain the FD observed on 2014 May 30. The observed FD was fitted quite well by ForbMod for all expansion modes using only the diffusion coefficient as a free parameter, where the diffusion parameter was found to correspond to an expected range of values. Our study shows that, in general, the model is able to explain the global properties of an FD caused by a flux rope and can thus be used to help understand the underlying physics in case studies.

  1. LakeMetabolizer: An R package for estimating lake metabolism from free-water oxygen using diverse statistical models

    Science.gov (United States)

    Winslow, Luke; Zwart, Jacob A.; Batt, Ryan D.; Dugan, Hilary; Woolway, R. Iestyn; Corman, Jessica; Hanson, Paul C.; Read, Jordan S.

    2016-01-01

    Metabolism is a fundamental process in ecosystems that crosses multiple scales of organization from individual organisms to whole ecosystems. To improve sharing and reuse of published metabolism models, we developed LakeMetabolizer, an R package for estimating lake metabolism from in situ time series of dissolved oxygen, water temperature, and, optionally, additional environmental variables. LakeMetabolizer implements 5 different metabolism models with diverse statistical underpinnings: bookkeeping, ordinary least squares, maximum likelihood, Kalman filter, and Bayesian. Each of these 5 metabolism models can be combined with 1 of 7 models for computing the coefficient of gas exchange across the air–water interface (k). LakeMetabolizer also features a variety of supporting functions that compute conversions and implement calculations commonly applied to raw data prior to estimating metabolism (e.g., oxygen saturation and optical conversion models). These tools have been organized into an R package that contains example data, example use-cases, and function documentation. The release package version is available on the Comprehensive R Archive Network (CRAN), and the full open-source GPL-licensed code is freely available for examination and extension online. With this unified, open-source, and freely available package, we hope to improve access and facilitate the application of metabolism in studies and management of lentic ecosystems.

  2. 13C based proteinogenic amino acid (PAA and metabolic flux ratio analysis of Lactococcus lactis reveals changes in pentose phosphate (PP pathway in response to agitation and temperature related stresses

    Directory of Open Access Journals (Sweden)

    Kamalrul Azlan Azizan

    2017-07-01

    Full Text Available Lactococcus lactis subsp. cremoris MG1363 is an important starter culture for dairy fermentation. During industrial fermentations, L. lactis is constantly exposed to stresses that affect the growth and performance of the bacterium. Although the response of L. lactis to several stresses has been described, the adaptation mechanisms at the level of in vivo fluxes have seldom been described. To gain insights into cellular metabolism, 13C metabolic flux analysis and gas chromatography mass spectrometry (GC-MS were used to measure the flux ratios of active pathways in the central metabolism of L. lactis when subjected to three conditions varying in temperature (30°C, 37°C and agitation (with and without agitation at 150 rpm. Collectively, the concentrations of proteinogenic amino acids (PAAs and free fatty acids (FAAs were compared, and Pearson correlation analysis (r was calculated to measure the pairwise relationship between PAAs. Branched chain and aromatic amino acids, threonine, serine, lysine and histidine were correlated strongly, suggesting changes in flux regulation in glycolysis, the pentose phosphate (PP pathway, malic enzyme and anaplerotic reaction catalysed by pyruvate carboxylase (pycA. Flux ratio analysis revealed that glucose was mainly converted by glycolysis, highlighting the stability of L. lactis’ central carbon metabolism despite different conditions. Higher flux ratios through oxaloacetate (OAA from pyruvate (PYR reaction in all conditions suggested the activation of pyruvate carboxylate (pycA in L. lactis, in response to acid stress during exponential phase. Subsequently, more significant flux ratio differences were seen through the oxidative and non-oxidative pentose phosphate (PP pathways, malic enzyme, and serine and C1 metabolism, suggesting NADPH requirements in response to environmental stimuli. These reactions could play an important role in optimization strategies for metabolic engineering in L. lactis. Overall

  3. 13C based proteinogenic amino acid (PAA) and metabolic flux ratio analysis of Lactococcus lactis reveals changes in pentose phosphate (PP) pathway in response to agitation and temperature related stresses.

    Science.gov (United States)

    Azizan, Kamalrul Azlan; Ressom, Habtom W; Mendoza, Eduardo R; Baharum, Syarul Nataqain

    2017-01-01

    Lactococcus lactis subsp. cremoris MG1363 is an important starter culture for dairy fermentation. During industrial fermentations, L. lactis is constantly exposed to stresses that affect the growth and performance of the bacterium. Although the response of L. lactis to several stresses has been described, the adaptation mechanisms at the level of in vivo fluxes have seldom been described. To gain insights into cellular metabolism, 13 C metabolic flux analysis and gas chromatography mass spectrometry (GC-MS) were used to measure the flux ratios of active pathways in the central metabolism of L. lactis when subjected to three conditions varying in temperature (30°C, 37°C) and agitation (with and without agitation at 150 rpm). Collectively, the concentrations of proteinogenic amino acids (PAAs) and free fatty acids (FAAs) were compared, and Pearson correlation analysis ( r ) was calculated to measure the pairwise relationship between PAAs. Branched chain and aromatic amino acids, threonine, serine, lysine and histidine were correlated strongly, suggesting changes in flux regulation in glycolysis, the pentose phosphate (PP) pathway, malic enzyme and anaplerotic reaction catalysed by pyruvate carboxylase (pycA). Flux ratio analysis revealed that glucose was mainly converted by glycolysis, highlighting the stability of L. lactis' central carbon metabolism despite different conditions. Higher flux ratios through oxaloacetate (OAA) from pyruvate (PYR) reaction in all conditions suggested the activation of pyruvate carboxylate (pycA) in L. lactis , in response to acid stress during exponential phase. Subsequently, more significant flux ratio differences were seen through the oxidative and non-oxidative pentose phosphate (PP) pathways, malic enzyme, and serine and C1 metabolism, suggesting NADPH requirements in response to environmental stimuli. These reactions could play an important role in optimization strategies for metabolic engineering in L. lactis . Overall, the

  4. 13C based proteinogenic amino acid (PAA) and metabolic flux ratio analysis of Lactococcus lactis reveals changes in pentose phosphate (PP) pathway in response to agitation and temperature related stresses

    Science.gov (United States)

    2017-01-01

    Lactococcus lactis subsp. cremoris MG1363 is an important starter culture for dairy fermentation. During industrial fermentations, L. lactis is constantly exposed to stresses that affect the growth and performance of the bacterium. Although the response of L. lactis to several stresses has been described, the adaptation mechanisms at the level of in vivo fluxes have seldom been described. To gain insights into cellular metabolism, 13C metabolic flux analysis and gas chromatography mass spectrometry (GC-MS) were used to measure the flux ratios of active pathways in the central metabolism of L. lactis when subjected to three conditions varying in temperature (30°C, 37°C) and agitation (with and without agitation at 150 rpm). Collectively, the concentrations of proteinogenic amino acids (PAAs) and free fatty acids (FAAs) were compared, and Pearson correlation analysis (r) was calculated to measure the pairwise relationship between PAAs. Branched chain and aromatic amino acids, threonine, serine, lysine and histidine were correlated strongly, suggesting changes in flux regulation in glycolysis, the pentose phosphate (PP) pathway, malic enzyme and anaplerotic reaction catalysed by pyruvate carboxylase (pycA). Flux ratio analysis revealed that glucose was mainly converted by glycolysis, highlighting the stability of L. lactis’ central carbon metabolism despite different conditions. Higher flux ratios through oxaloacetate (OAA) from pyruvate (PYR) reaction in all conditions suggested the activation of pyruvate carboxylate (pycA) in L. lactis, in response to acid stress during exponential phase. Subsequently, more significant flux ratio differences were seen through the oxidative and non-oxidative pentose phosphate (PP) pathways, malic enzyme, and serine and C1 metabolism, suggesting NADPH requirements in response to environmental stimuli. These reactions could play an important role in optimization strategies for metabolic engineering in L. lactis. Overall, the

  5. A DOUBLE-RING ALGORITHM FOR MODELING SOLAR ACTIVE REGIONS: UNIFYING KINEMATIC DYNAMO MODELS AND SURFACE FLUX-TRANSPORT SIMULATIONS

    International Nuclear Information System (INIS)

    Munoz-Jaramillo, Andres; Martens, Petrus C. H.; Nandy, Dibyendu; Yeates, Anthony R.

    2010-01-01

    The emergence of tilted bipolar active regions (ARs) and the dispersal of their flux, mediated via processes such as diffusion, differential rotation, and meridional circulation, is believed to be responsible for the reversal of the Sun's polar field. This process (commonly known as the Babcock-Leighton mechanism) is usually modeled as a near-surface, spatially distributed α-effect in kinematic mean-field dynamo models. However, this formulation leads to a relationship between polar field strength and meridional flow speed which is opposite to that suggested by physical insight and predicted by surface flux-transport simulations. With this in mind, we present an improved double-ring algorithm for modeling the Babcock-Leighton mechanism based on AR eruption, within the framework of an axisymmetric dynamo model. Using surface flux-transport simulations, we first show that an axisymmetric formulation-which is usually invoked in kinematic dynamo models-can reasonably approximate the surface flux dynamics. Finally, we demonstrate that our treatment of the Babcock-Leighton mechanism through double-ring eruption leads to an inverse relationship between polar field strength and meridional flow speed as expected, reconciling the discrepancy between surface flux-transport simulations and kinematic dynamo models.

  6. Simulation of Forest Carbon Fluxes Using Model Incorporation and Data Assimilation

    OpenAIRE

    Min Yan; Xin Tian; Zengyuan Li; Erxue Chen; Xufeng Wang; Zongtao Han; Hong Sun

    2016-01-01

    This study improved simulation of forest carbon fluxes in the Changbai Mountains with a process-based model (Biome-BGC) using incorporation and data assimilation. Firstly, the original remote sensing-based MODIS MOD_17 GPP (MOD_17) model was optimized using refined input data and biome-specific parameters. The key ecophysiological parameters of the Biome-BGC model were determined through the Extended Fourier Amplitude Sensitivity Test (EFAST) sensitivity analysis. Then the optimized MOD_17 mo...

  7. Mechanistic modeling of aberrant energy metabolism in human disease

    Directory of Open Access Journals (Sweden)

    Vineet eSangar

    2012-10-01

    Full Text Available Dysfunction in energy metabolism—including in pathways localized to the mitochondria—has been implicated in the pathogenesis of a wide array of disorders, ranging from cancer to neurodegenerative diseases to type II diabetes. The inherent complexities of energy and mitochondrial metabolism present a significant obstacle in the effort to understand the role that these molecular processes play in the development of disease. To help unravel these complexities, systems biology methods have been applied to develop an array of computational metabolic models, ranging from mitochondria-specific processes to genome-scale cellular networks. These constraint-based models can efficiently simulate aspects of normal and aberrant metabolism in various genetic and environmental conditions. Development of these models leverages—and also provides a powerful means to integrate and interpret—information from a wide range of sources including genomics, proteomics, metabolomics, and enzyme kinetics. Here, we review a variety of mechanistic modeling studies that explore metabolic functions, deficiency disorders, and aberrant biochemical pathways in mitochondria and related regions in the cell.

  8. Metabolism related toxicity of diclofenac in yeast as model system

    NARCIS (Netherlands)

    van Leeuwen, J.S.; Vredenburg, G.; Dragovic, S.; Tjong, T.F.; Vos, J.C.; Vermeulen, N.P.E.

    2010-01-01

    Diclofenac is a widely used drug that can cause serious hepatotoxicity, which has been linked to metabolism by cytochrome P450s (P450). To investigate the role of oxidative metabolites in diclofenac toxicity, a model for P450-related toxicity was set up in Saccharomyces cerevisiae. We expressed a

  9. Network thermodynamic curation of human and yeast genome-scale metabolic models.

    Science.gov (United States)

    Martínez, Verónica S; Quek, Lake-Ee; Nielsen, Lars K

    2014-07-15

    Genome-scale models are used for an ever-widening range of applications. Although there has been much focus on specifying the stoichiometric matrix, the predictive power of genome-scale models equally depends on reaction directions. Two-thirds of reactions in the two eukaryotic reconstructions Homo sapiens Recon 1 and Yeast 5 are specified as irreversible. However, these specifications are mainly based on biochemical textbooks or on their similarity to other organisms and are rarely underpinned by detailed thermodynamic analysis. In this study, a to our knowledge new workflow combining network-embedded thermodynamic and flux variability analysis was used to evaluate existing irreversibility constraints in Recon 1 and Yeast 5 and to identify new ones. A total of 27 and 16 new irreversible reactions were identified in Recon 1 and Yeast 5, respectively, whereas only four reactions were found with directions incorrectly specified against thermodynamics (three in Yeast 5 and one in Recon 1). The workflow further identified for both models several isolated internal loops that require further curation. The framework also highlighted the need for substrate channeling (in human) and ATP hydrolysis (in yeast) for the essential reaction catalyzed by phosphoribosylaminoimidazole carboxylase in purine metabolism. Finally, the framework highlighted differences in proline metabolism between yeast (cytosolic anabolism and mitochondrial catabolism) and humans (exclusively mitochondrial metabolism). We conclude that network-embedded thermodynamics facilitates the specification and validation of irreversibility constraints in compartmentalized metabolic models, at the same time providing further insight into network properties. Copyright © 2014 Biophysical Society. Published by Elsevier Inc. All rights reserved.

  10. Discussion about modeling the effects of neutron flux exposure for nuclear reactor core analysis

    International Nuclear Information System (INIS)

    Vondy, D.R.

    1986-04-01

    Methods used to calculate the effects of exposure to a neutron flux are described. The modeling of the nuclear-reactor core history presents an analysis challenge. The nuclide chain equations must be solved, and some of the methods in use for this are described. Techniques for treating reactor-core histories are discussed and evaluated

  11. Regularized Biot-Savart Laws for Modeling Magnetic Configurations with Flux Ropes

    Science.gov (United States)

    Titov, V. S.; Downs, C.; Mikic, Z.; Torok, T.; Linker, J.

    2017-12-01

    Many existing models assume that magnetic flux ropes play a key role in solar flares and coronal mass ejections (CMEs). It is therefore important to develop efficient methods for constructing flux-rope configurations constrained by observed magnetic data and the initial morphology of CMEs. For this purpose, we have derived and implemented a compact analytical form that represents the magnetic field of a thin flux rope with an axis of arbitrary shape and a circular cross-section. This form implies that the flux rope carries axial current I and axial flux F, so that the respective magnetic field is the curl of the sum of toroidal and poloidal vector potentials proportional to I and F, respectively. We expressed the vector potentials in terms of modified Biot-Savart laws whose kernels are regularized at the axis in such a way that these laws define a cylindrical force-free flux rope with a parabolic profile of the axial current density, when the axis is straight. For the cases we have studied so far, we determined the shape of the rope axis by following the polarity inversion line of the eruptions' source region, using observed magnetograms. The height variation along the axis and other flux-rope parameters are estimated by means of potential field extrapolations. Using this heuristic approach, we were able to construct pre-eruption configurations for the 2009 February13 and 2011 October 1 CME events. These applications demonstrate the flexibility and efficiency of our new method for energizing pre-eruptive configurations in MHD simulations of CMEs. We discuss possible ways of optimizing the axis paths and other extensions of the method in order to make it more useful and robust. Research supported by NSF, NASA's HSR and LWS Programs, and AFOSR.

  12. Generalized framework for context-specific metabolic model extraction methods

    Directory of Open Access Journals (Sweden)

    Semidán eRobaina Estévez

    2014-09-01

    Full Text Available Genome-scale metabolic models are increasingly applied to investigate the physiology not only of simple prokaryotes, but also eukaryotes, such as plants, characterized with compartmentalized cells of multiple types. While genome-scale models aim at including the entirety of known metabolic reactions, mounting evidence has indicated that only a subset of these reactions is active in a given context, including: developmental stage, cell type, or environment. As a result, several methods have been proposed to reconstruct context-specific models from existing genome-scale models by integrating various types of high-throughput data. Here we present a mathematical framework that puts all existing methods under one umbrella and provides the means to better understand their functioning, highlight similarities and differences, and to help users in selecting a most suitable method for an application.

  13. Measurement and modelling ozone fluxes over a cut and fertilized grassland

    Directory of Open Access Journals (Sweden)

    R. Mészáros

    2009-10-01

    Full Text Available During the GRAMINAE Integrated Experiment between 20 May and 15 June 2000, the ozone flux was measured by the eddy covariance method above intensively managed grassland in Braunschweig, northern Germany. Three different phases of vegetation were covered during the measuring campaign: tall grass canopy before cut (29 May 2000, short grass after cut, and re-growing vegetation after fertilization (5 June 2000. Results show that beside weather conditions, the agricultural activities significantly influenced the O3 fluxes. After the cut the daytime average of the deposition velocity (vd decreased from 0.44 cm s−1 to 0.26 cm s−1 and increased again to 0.32 cm s−1 during the third period. Detailed model calculations were carried out to estimate deposition velocity and ozone flux. The model captures the general diurnal patter of deposition, with vd daytime values of 0.52, 0.24, and 0.35 cm s−1 in the first, second and third period, respectively. Thus the model predicts a stronger response to the cut than the measurements, which is nevertheless smaller than expected on the basis of change in leaf area. The results show that both cut and fertilization have complex impacts on fluxes. Reduction of vegetation by cutting decreased the stomatal flux initially greatly, but the stomatal flux recovered to 80% of its original value within a week. At the same time, the non-stomatal flux appears to have increased directly after the cut, which the model partially explains by an increase in the deposition to the soil. A missing sink after the cut may be the chemical interaction with biogenic volatile organic compounds released after the cut and exposed senescent plant parts, or the increase in soil NO emissions after fertilization. Increased canopy temperatures may also have promoted ozone destruction on leaf surfaces. These results demonstrate the importance of canopy

  14. Critical heat flux measurements in small-diameter tubes using R12 as model fluid

    International Nuclear Information System (INIS)

    Mueller-Menzel, T.

    1987-01-01

    Results of critical heat flux measurements are reported for vertical upflow of Refrigerant 12 at high mass fluxes and high pressures in small diameter tubes. The data are transformed into water data using a scaling law, which is verified by means of a new analysis. An error estimation includes the error of the scaling law. Special phenomena ('limiting quality', 'upstream boiling crisis') are explained by theoretical models. The applicability of existing correlations is checked and a new CHF-table for small diameter tubes is presented. With 41 figs., 12 tabs [de

  15. Uncertainty and Sensitivity of Alternative Rn-222 Flux Density Models Used in Performance Assessment

    Energy Technology Data Exchange (ETDEWEB)

    Greg J. Shott, Vefa Yucel, Lloyd Desotell

    2007-06-01

    Performance assessments for the Area 5 Radioactive Waste Management Site on the Nevada Test Site have used three different mathematical models to estimate Rn-222 flux density. This study describes the performance, uncertainty, and sensitivity of the three models which include the U.S. Nuclear Regulatory Commission Regulatory Guide 3.64 analytical method and two numerical methods. The uncertainty of each model was determined by Monte Carlo simulation using Latin hypercube sampling. The global sensitivity was investigated using Morris one-at-time screening method, sample-based correlation and regression methods, the variance-based extended Fourier amplitude sensitivity test, and Sobol's sensitivity indices. The models were found to produce similar estimates of the mean and median flux density, but to have different uncertainties and sensitivities. When the Rn-222 effective diffusion coefficient was estimated using five different published predictive models, the radon flux density models were found to be most sensitive to the effective diffusion coefficient model selected, the emanation coefficient, and the radionuclide inventory. Using a site-specific measured effective diffusion coefficient significantly reduced the output uncertainty. When a site-specific effective-diffusion coefficient was used, the models were most sensitive to the emanation coefficient and the radionuclide inventory.

  16. Sabots, Obturator and Gas-In-Launch Tube Techniques for Heat Flux Models in Ballistic Ranges

    Science.gov (United States)

    Bogdanoff, David W.; Wilder, Michael C.

    2013-01-01

    For thermal protection system (heat shield) design for space vehicle entry into earth and other planetary atmospheres, it is essential to know the augmentation of the heat flux due to vehicle surface roughness. At the NASA Ames Hypervelocity Free Flight Aerodynamic Facility (HFFAF) ballistic range, a campaign of heat flux studies on rough models, using infrared camera techniques, has been initiated. Several phenomena can interfere with obtaining good heat flux data when using this measuring technique. These include leakage of the hot drive gas in the gun barrel through joints in the sabot (model carrier) to create spurious thermal imprints on the model forebody, deposition of sabot material on the model forebody, thereby changing the thermal properties of the model surface and unknown in-barrel heating of the model. This report presents developments in launch techniques to greatly reduce or eliminate these problems. The techniques include the use of obturator cups behind the launch package, enclosed versus open front sabot designs and the use of hydrogen gas in the launch tube. Attention also had to be paid to the problem of the obturator drafting behind the model and impacting the model. Of the techniques presented, the obturator cups and hydrogen in the launch tube were successful when properly implemented

  17. Uncertainty and Sensitivity of Alternative Rn-222 Flux Density Models Used in Performance Assessment

    International Nuclear Information System (INIS)

    Greg J. Shott, Vefa Yucel, Lloyd Desotell Non-Nstec Authors: G. Pyles and Jon Carilli

    2007-01-01

    Performance assessments for the Area 5 Radioactive Waste Management Site on the Nevada Test Site have used three different mathematical models to estimate Rn-222 flux density. This study describes the performance, uncertainty, and sensitivity of the three models which include the U.S. Nuclear Regulatory Commission Regulatory Guide 3.64 analytical method and two numerical methods. The uncertainty of each model was determined by Monte Carlo simulation using Latin hypercube sampling. The global sensitivity was investigated using Morris one-at-time screening method, sample-based correlation and regression methods, the variance-based extended Fourier amplitude sensitivity test, and Sobol's sensitivity indices. The models were found to produce similar estimates of the mean and median flux density, but to have different uncertainties and sensitivities. When the Rn-222 effective diffusion coefficient was estimated using five different published predictive models, the radon flux density models were found to be most sensitive to the effective diffusion coefficient model selected, the emanation coefficient, and the radionuclide inventory. Using a site-specific measured effective diffusion coefficient significantly reduced the output uncertainty. When a site-specific effective-diffusion coefficient was used, the models were most sensitive to the emanation coefficient and the radionuclide inventory

  18. Computational Flux Balance Analysis Predicts that Stimulation of Energy Metabolism in Astrocytes and their Metabolic Interactions with Neurons Depend on Uptake of K(+) Rather than Glutamate

    DEFF Research Database (Denmark)

    DiNuzzo, Mauro; Giove, Federico; Maraviglia, Bruno

    2017-01-01

    obtained by (13)C-NMR spectroscopy in rodent brain. When simulated data matched experiments as well as biophysical calculations, the stoichiometry for voltage/ligand-gated Na(+) and K(+) fluxes generated by neuronal activity was close to a 1:1 relationship, and specifically 63/58 Na(+)/K(+) ions per...

  19. Numerical modelling of landscape and sediment flux response to precipitation rate change

    Science.gov (United States)

    Armitage, John J.; Whittaker, Alexander C.; Zakari, Mustapha; Campforts, Benjamin

    2018-02-01

    Laboratory-scale experiments of erosion have demonstrated that landscapes have a natural (or intrinsic) response time to a change in precipitation rate. In the last few decades there has been growth in the development of numerical models that attempt to capture landscape evolution over long timescales. However, there is still an uncertainty regarding the validity of the basic assumptions of mass transport that are made in deriving these models. In this contribution we therefore return to a principal assumption of sediment transport within the mass balance for surface processes; we explore the sensitivity of the classic end-member landscape evolution models and the sediment fluxes they produce to a change in precipitation rates. One end-member model takes the mathematical form of a kinetic wave equation and is known as the stream power model, in which sediment is assumed to be transported immediately out of the model domain. The second end-member model is the transport model and it takes the form of a diffusion equation, assuming that the sediment flux is a function of the water flux and slope. We find that both of these end-member models have a response time that has a proportionality to the precipitation rate that follows a negative power law. However, for the stream power model the exponent on the water flux term must be less than one, and for the transport model the exponent must be greater than one, in order to match the observed concavity of natural systems. This difference in exponent means that the transport model generally responds more rapidly to an increase in precipitation rates, on the order of 105 years for post-perturbation sediment fluxes to return to within 50 % of their initial values, for theoretical landscapes with a scale of 100×100 km. Additionally from the same starting conditions, the amplitude of the sediment flux perturbation in the transport model is greater, with much larger sensitivity to catchment size. An important finding is that

  20. Numerical modelling of landscape and sediment flux response to precipitation rate change

    Directory of Open Access Journals (Sweden)

    J. J. Armitage

    2018-02-01

    Full Text Available Laboratory-scale experiments of erosion have demonstrated that landscapes have a natural (or intrinsic response time to a change in precipitation rate. In the last few decades there has been growth in the development of numerical models that attempt to capture landscape evolution over long timescales. However, there is still an uncertainty regarding the validity of the basic assumptions of mass transport that are made in deriving these models. In this contribution we therefore return to a principal assumption of sediment transport within the mass balance for surface processes; we explore the sensitivity of the classic end-member landscape evolution models and the sediment fluxes they produce to a change in precipitation rates. One end-member model takes the mathematical form of a kinetic wave equation and is known as the stream power model, in which sediment is assumed to be transported immediately out of the model domain. The second end-member model is the transport model and it takes the form of a diffusion equation, assuming that the sediment flux is a function of the water flux and slope. We find that both of these end-member models have a response time that has a proportionality to the precipitation rate that follows a negative power law. However, for the stream power model the exponent on the water flux term must be less than one, and for the transport model the exponent must be greater than one, in order to match the observed concavity of natural systems. This difference in exponent means that the transport model generally responds more rapidly to an increase in precipitation rates, on the order of 105 years for post-perturbation sediment fluxes to return to within 50 % of their initial values, for theoretical landscapes with a scale of 100×100 km. Additionally from the same starting conditions, the amplitude of the sediment flux perturbation in the transport model is greater, with much larger sensitivity to catchment size. An

  1. A trigger mechanism for the emerging flux model of solar flares

    International Nuclear Information System (INIS)

    Tur, T.J.; Priest, E.R.

    1978-01-01

    The energetics of a current sheet that forms between newly emerging flux and an ambient field are considered. As more and more flux emerges, so the sheet rises in the solar atmosphere. The various contributions to the thermal energy balance in the sheet approximated and the resulting equation solved for the internal temperature of the sheet. It is found that, for certain choices of the ambient magnetic field strength and velocity, the internal temperature increases until, when the sheet reaches some critical height, no neighbouring equilibrium state exists. The temperature than increases rapidly, seeking a hotter branch of the solution curve. During this dynamic heating the threshold temperature for the onset of plasma microinstabilities may be attained. It is suggested that this may be a suitable trigger mechanism for the recently proposed 'emerging flux' model of a solar flare. (Auth.)

  2. Flux schemes for the two-fluid models of the trio-U code

    International Nuclear Information System (INIS)

    Kumbaro, A.; Seignole, V.; Ghidaglia, J.M.

    2000-01-01

    To solve the non-conservative system of the two-phase flow model in the TRIO-U two-phase flow module, a fully unstructured finite volume formulation is chosen, and the discretization is based on the concept of flux-scheme. Our method allows to determine whether hyperbolicity is necessary to have stable and convergent numerical computations. We discuss the necessity or not to consider all the differential transfer terms between the two-phases in the up-winding of the flux. Numerical results are presented in order to study out the influence of the pressure interface term in the stability, as well as in the up-winding of the flux. (author)

  3. Global surface wind and flux fields from model assimilation of Seasat data

    Science.gov (United States)

    Atlas, R.; Busalacchi, A. J.; Kalnay, E.; Bloom, S.; Ghil, M.

    1986-01-01

    Procedures for dealiasing Seasat data and developing global surface wind and latent and sensible heat flux fields are discussed. Seasat data from September 20, 1978 was dealiased using the Goddard Laboratory for Atmospheres (GLA) analysis/forecast system. The wind data obtained with the objective GLA forecast model are compared to the data subjectively dealiased by Peteherych et al. (1984) and Hoffman (1982, 1984). The GLA procedure is also verified using simulated Seasat data. The areas of high and low heat fluxes and cyclonic and anticyclonic wind stresses detected in the generated fields are analyzed and compared to climatological fields. It is observed that there is good correlation between the time-averaged analyses of wind stress obtained subjectively and objectively, and the monthly mean wind stress and latent fluxes agree with climatological fields and atmospheric and oceanic features.

  4. Modelling and analysis of flux surface mapping experiments on W7-X

    Science.gov (United States)

    Lazerson, Samuel; Otte, Matthias; Bozhenkov, Sergey; Sunn Pedersen, Thomas; Bräuer, Torsten; Gates, David; Neilson, Hutch; W7-X Team

    2015-11-01

    The measurement and compensation of error fields in W7-X will be key to the device achieving high beta steady state operations. Flux surface mapping utilizes the vacuum magnetic flux surfaces, a feature unique to stellarators and heliotrons, to allow direct measurement of magnetic topology, and thereby allows a highly accurate determination of remnant magnetic field errors. As will be reported separately at this meeting, the first measurements confirming the existence of nested flux surfaces in W7-X have been made. In this presentation, a synthetic diagnostic for the flux surface mapping diagnostic is presented. It utilizes Poincaré traces to construct an image of the flux surface consistent with the measured camera geometry, fluorescent rod sweep plane, and emitter beam position. Forward modeling of the high-iota configuration will be presented demonstrating an ability to measure the intrinsic error field using the U.S. supplied trim coil system on W7-X, and a first experimental assessment of error fields in W7-X will be presented. This work has been authored by Princeton University under Contract Number DE-AC02-09CH11466 with the US Department of Energy.

  5. Metabolism

    Science.gov (United States)

    ... lin), which signals cells to increase their anabolic activities. Metabolism is a complicated chemical process, so it's not ... how those enzymes or hormones work. When the metabolism of body chemicals is ... Hyperthyroidism (pronounced: hi-per-THIGH-roy-dih-zum). Hyperthyroidism ...

  6. Metabolic modeling of synthesis gas fermentation in bubble column reactors.

    Science.gov (United States)

    Chen, Jin; Gomez, Jose A; Höffner, Kai; Barton, Paul I; Henson, Michael A

    2015-01-01

    A promising route to renewable liquid fuels and chemicals is the fermentation of synthesis gas (syngas) streams to synthesize desired products such as ethanol and 2,3-butanediol. While commercial development of syngas fermentation technology is underway, an unmet need is the development of integrated metabolic and transport models for industrially relevant syngas bubble column reactors. We developed and evaluated a spatiotemporal metabolic model for bubble column reactors with the syngas fermenting bacterium Clostridium ljungdahlii as the microbial catalyst. Our modeling approach involved combining a genome-scale reconstruction of C. ljungdahlii metabolism with multiphase transport equations that govern convective and dispersive processes within the spatially varying column. The reactor model was spatially discretized to yield a large set of ordinary differential equations (ODEs) in time with embedded linear programs (LPs) and solved using the MATLAB based code DFBAlab. Simulations were performed to analyze the effects of important process and cellular parameters on key measures of reactor performance including ethanol titer, ethanol-to-acetate ratio, and CO and H2 conversions. Our computational study demonstrated that mathematical modeling provides a complementary tool to experimentation for understanding, predicting, and optimizing syngas fermentation reactors. These model predictions could guide future cellular and process engineering efforts aimed at alleviating bottlenecks to biochemical production in syngas bubble column reactors.

  7. Model for GCR-particle fluxes in stony meteorites and production rates of cosmogenic nuclides

    International Nuclear Information System (INIS)

    Reedy, R.C.

    1984-01-01

    A model is presented for the differential fluxes of galactic-cosmic-ray (GCR) particles with energies above 1 MeV inside any spherical stony meteorite as a function of the meteorite's radius and the sample's depth. This model is based on the Reedy-Arnold equations for the energy-dependent fluxes of GCR particles in the moon and is an extension of flux parameters that were derived for several meteorites of various sizes. This flux is used to calculate the production rates of many cosmogenic nuclides as a function of radius and depth. The peak production rates for most nuclides made by the reactions of energetic GCR particles occur near the centers of meteorites with radii of 40 to 70 g cm -2 . Although the model has some limitations, it reproduces well the basic trends for the depth-dependent production of cosmogenic nuclides in stony meteorites of various radii. These production profiles agree fairly well with measurements of cosmogenic nuclides in meteorites. Some of these production profiles are different than those calculated by others. The chemical dependence of the production rates for several nuclides varies with size and depth. 25 references, 8 figures

  8. Comparison of depth-averaged concentration and bed load flux sediment transport models of dam-break flow

    Directory of Open Access Journals (Sweden)

    Jia-heng Zhao

    2017-10-01

    Full Text Available This paper presents numerical simulations of dam-break flow over a movable bed. Two different mathematical models were compared: a fully coupled formulation of shallow water equations with erosion and deposition terms (a depth-averaged concentration flux model, and shallow water equations with a fully coupled Exner equation (a bed load flux model. Both models were discretized using the cell-centered finite volume method, and a second-order Godunov-type scheme was used to solve the equations. The numerical flux was calculated using a Harten, Lax, and van Leer approximate Riemann solver with the contact wave restored (HLLC. A novel slope source term treatment that considers the density change was introduced to the depth-averaged concentration flux model to obtain higher-order accuracy. A source term that accounts for the sediment flux was added to the bed load flux model to reflect the influence of sediment movement on the momentum of the water. In a one-dimensional test case, a sensitivity study on different model parameters was carried out. For the depth-averaged concentration flux model, Manning's coefficient and sediment porosity values showed an almost linear relationship with the bottom change, and for the bed load flux model, the sediment porosity was identified as the most sensitive parameter. The capabilities and limitations of both model concepts are demonstrated in a benchmark experimental test case dealing with dam-break flow over variable bed topography.

  9. Metabolic modeling to identify engineering targets for Komagataella phaffii: The effect of biomass composition on gene target identification.

    Science.gov (United States)

    Cankorur-Cetinkaya, Ayca; Dikicioglu, Duygu; Oliver, Stephen G

    2017-11-01

    Genome-scale metabolic models are valuable tools for the design of novel strains of industrial microorganisms, such as Komagataella phaffii (syn. Pichia pastoris). However, as is the case for many industrial microbes, there is no executable metabolic model for K. phaffiii that confirms to current standards by providing the metabolite and reactions IDs, to facilitate model extension and reuse, and gene-reaction associations to enable identification of targets for genetic manipulation. In order to remedy this deficiency, we decided to reconstruct the genome-scale metabolic model of K. phaffii by reconciling the extant models and performing extensive manual curation in order to construct an executable model (Kp.1.0) that conforms to current standards. We then used this model to study the effect of biomass composition on the predictive success of the model. Twelve different biomass compositions obtained from published empirical data obtained under a range of growth conditions were employed in this investigation. We found that the success of Kp1.0 in predicting both gene essentiality and growth characteristics was relatively unaffected by biomass composition. However, we found that biomass composition had a profound effect on the distribution of the fluxes involved in lipid, DNA, and steroid biosynthetic processes, cellular alcohol metabolic process, and oxidation-reduction process. Furthermore, we investigated the effect of biomass composition on the identification of suitable target genes for strain development. The analyses revealed that a