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

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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...

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

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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.

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

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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

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

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.

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.

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

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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.

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

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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.

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.

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

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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.

Metabolic flux analysis of heterotrophic growth in Chlamydomonas reinhardtii.

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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.

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

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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.

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...

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

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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.

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

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

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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

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

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.

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.

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

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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.

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

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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.

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.

EL-2 reactor: Thermal neutron flux distribution

International Nuclear Information System (INIS)

Rousseau, A.; Genthon, J.P.

1958-01-01

The flux distribution of thermal neutrons in EL-2 reactor is studied. The reactor core and lattices are described as well as the experimental reactor facilities, in particular, the experimental channels and special facilities. The measurement shows that the thermal neutron flux increases in the central channel when enriched uranium is used in place of natural uranium. However the thermal neutron flux is not perturbed in the other reactor channels by the fuel modification. The macroscopic flux distribution is measured according the radial positioning of fuel rods. The longitudinal neutron flux distribution in a fuel rod is also measured and shows no difference between enriched and natural uranium fuel rods. In addition, measurements of the flux distribution have been effectuated for rods containing other material as steel or aluminium. The neutron flux distribution is also studied in all the experimental channels as well as in the thermal column. The determination of the distribution of the thermal neutron flux in all experimental facilities, the thermal column and the fuel channels has been made with a heavy water level of 1825 mm and is given for an operating power of 1000 kW. (M.P.)

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

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

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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.

(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.

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

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

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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.

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

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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

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

Science.gov (United States)

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.

Maintenance metabolism and carbon fluxes in Bacillus species

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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

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.

EL-2 reactor: Thermal neutron flux distribution; EL-2: Repartition du flux de neutrons thermiques

Energy Technology Data Exchange (ETDEWEB)

Rousseau, A; Genthon, J P [Commissariat a l' Energie Atomique, Saclay (France). Centre d' Etudes Nucleaires

1958-07-01

The flux distribution of thermal neutrons in EL-2 reactor is studied. The reactor core and lattices are described as well as the experimental reactor facilities, in particular, the experimental channels and special facilities. The measurement shows that the thermal neutron flux increases in the central channel when enriched uranium is used in place of natural uranium. However the thermal neutron flux is not perturbed in the other reactor channels by the fuel modification. The macroscopic flux distribution is measured according the radial positioning of fuel rods. The longitudinal neutron flux distribution in a fuel rod is also measured and shows no difference between enriched and natural uranium fuel rods. In addition, measurements of the flux distribution have been effectuated for rods containing other material as steel or aluminium. The neutron flux distribution is also studied in all the experimental channels as well as in the thermal column. The determination of the distribution of the thermal neutron flux in all experimental facilities, the thermal column and the fuel channels has been made with a heavy water level of 1825 mm and is given for an operating power of 1000 kW. (M.P.)

TRANSHEX, 2-D Thermal Neutron Flux Distribution from Epithermal Flux in Hexagonal Geometry

International Nuclear Information System (INIS)

Patrakka, E.

1994-01-01

1 - Description of program or function: TRANSHEX is a multigroup integral transport program that determines the thermal scalar flux distribution arising from a known epithermal flux in two- dimensional hexagonal geometry. 2 - Method of solution: The program solves the isotropic collision probability equations for a region-averaged scalar flux by an iterative method. Either a successive over-relaxation or an inner-outer iteration technique is applied. Flat flux collision probabilities between trigonal space regions with white boundary condition are utilized. The effect of epithermal flux is taken into consideration as a slowing-down source that is calculated for a given spatial distribution and 1/E energy dependence of the epithermal flux

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

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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

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.

Neutron flux distribution forecasting device of reactor

International Nuclear Information System (INIS)

Uematsu, Hitoshi

1991-01-01

A neutron flux distribution is forecast by using current data obtained from a reactor. That is, the device of the present invention comprises (1) a neutron flux monitor disposed in various positions in the reactor, (2) a forecasting means for calculating and forecasting a one-dimensional neutron flux distribution relative to imaginable events by using data obtained from the neutron flux monitor and physical models, and (3) a display means for displaying the results forecast in the forecasting means to a reactor operation console. Since the forecast values for the one-dimensional neutron flux distribution relative to the imaginable events are calculated in the device of the present invention by using data obtained from the neutron flux monitor and the physical models, the data as a base of the calculation are new and the period for calculating the forecast values can be shortened. Accordingly, although there is a worry of providing some errors in the forecast values, they can be utilized sufficiently as reference data. As a result, the reactor can be operated more appropriately. (I.N.)

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.

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)

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/.

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.

Effect of axial heat flux distribution on CHF

Energy Technology Data Exchange (ETDEWEB)

Park, Cheol

2000-10-01

Previous investigations for the effect of axial heat flux distributions on CHF and the prediction methods are reviewed and summarized. A total of 856 CHF data in a tube with a non-uniform axial heat flux distribution has been compiled from the articles and analyzed using the 1995 Groeneveld look-up table. The results showed that two representative correction factors, K5 of the look-up table and Tongs F factor, can be applied to describe the axial heat flux distribution effect on CHF. However, they overpredict slightly the measured CHF, depending on the quality and flux peak shape. Hence, a corrected K5 factor, which accounts for the axial heat flux distribution effect is suggested to correct these trends. It predicted the CHF power for the compiled data with an average error of 1.5% and a standard deviation of 10.3%, and also provides a reasonable prediction of CHF locations.

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.

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.

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)

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

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

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

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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.

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.

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...

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

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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.

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

An observer-theoretic approach to estimating neutron flux distribution

International Nuclear Information System (INIS)

Park, Young Ho; Cho, Nam Zin

1989-01-01

State feedback control provides many advantages such as stabilization and improved transient response. However, when the state feedback control is considered for spatial control of a nuclear reactor, it requires complete knowledge of the distributions of the system state variables. This paper describes a method for estimating the flux spatial distribution using only limited flux measurements. It is based on the Luenberger observer in control theory, extended to the distributed parameter systems such as the space-time reactor dynamics equation. The results of the application of the method to simple reactor models showed that the flux distribution is estimated by the observer very efficiently using information from only a few sensors

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

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

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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

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.

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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.

Distribution Functions of Sizes and Fluxes Determined from Supra-Arcade Downflows

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McKenzie, D.; Savage, S.

2011-01-01

The frequency distributions of sizes and fluxes of supra-arcade downflows (SADs) provide information about the process of their creation. For example, a fractal creation process may be expected to yield a power-law distribution of sizes and/or fluxes. We examine 120 cross-sectional areas and magnetic flux estimates found by Savage & McKenzie for SADs, and find that (1) the areas are consistent with a log-normal distribution and (2) the fluxes are consistent with both a log-normal and an exponential distribution. Neither set of measurements is compatible with a power-law distribution nor a normal distribution. As a demonstration of the applicability of these findings to improved understanding of reconnection, we consider a simple SAD growth scenario with minimal assumptions, capable of producing a log-normal distribution.

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

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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.

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.

The epithermal neutron-flux distribution in the reactor RA - Vinca

International Nuclear Information System (INIS)

Marinkov, V.; Bikit, I.; Martinc, R.; Veskovic, M.; Slivka, J.; Vaderna, S.

1987-01-01

The distribution of the epithermal neutron flux in the reactor RA - Vinca has been measured by means of Zr - activation detectors. In the channel VK-8 non-homogeneous flux distribution was observed (author) [sr

Modeling of Drift Effects on Solar Tower Concentrated Flux Distributions

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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.

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

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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

Device for measuring neutron-flux distribution density

International Nuclear Information System (INIS)

Rozenbljum, N.D.; Mitelman, M.G.; Kononovich, A.A.; Kirsanov, V.S.; Zagadkin, V.A.

1977-01-01

An arrangement is described for measuring the distribution of neutron flux density over the height of a nuclear reactor core and which may be used for monitoring energy release or for detecting deviations of neutron flux from an optimal level so that subsequent balance can be achieved. It avoids mutual interference of detectors. Full constructional details are given. (UK)

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...

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

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

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

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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

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 .

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...

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.

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.

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.

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

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...

Computational Platform for Flux Analysis Using 13C-Label Tracing- Phase I SBIR Final Report

Energy Technology Data Exchange (ETDEWEB)

Van Dien, Stephen J.

2005-04-12

Isotopic label tracing is a powerful experimental technique that can be combined with metabolic models to quantify metabolic fluxes in an organism under a particular set of growth conditions. In this work we constructed a genome-scale metabolic model of Methylobacterium extorquens, a facultative methylotroph with potential application in the production of useful chemicals from methanol. A series of labeling experiments were performed using 13C-methanol, and the resulting distribution of labeled carbon in the proteinogenic amino acids was determined by mass spectrometry. Algorithms were developed to analyze this data in context of the metabolic model, yielding flux distributions for wild-type and several engineered strains of M. extorquens. These fluxes were compared to those predicted by model simulation alone, and also integrated with microarray data to give an improved understanding of the metabolic physiology of this organism.

Investigating The Neutron Flux Distribution Of The Miniature Neutron Source Reactor MNSR Type

International Nuclear Information System (INIS)

Nguyen Hoang Hai; Do Quang Binh

2011-01-01

Neutron flux distribution is the important characteristic of nuclear reactor. In this article, four energy group neutron flux distributions of the miniature neutron source reactor MNSR type versus radial and axial directions are investigated in case the control rod is fully withdrawn. In addition, the effect of control rod positions on the thermal neutron flux distribution is also studied. The group constants for all reactor components are generated by the WIMSD code, and the neutron flux distributions are calculated by the CITATION code. The results show that the control rod positions only affect in the planning area for distribution in the region around the control rod. (author)

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....

Measurement of the thermal flux distribution in the IEA-R1 reactor

International Nuclear Information System (INIS)

Tangari, C.M.; Moreira, J.M.L.; Jerez, R.

1986-01-01

The knowledge of the neutron flux distribution in research reactors is important because it gives the power distribution over the core, and it provides better conditions to perform experiments and sample irradiations. The measured neutron flux distribution can also be of interest as a means of comparison for the calculational methods of reactor analysis currently in use at this institute. The thermal neutron flux distribution of the IEA-R1 reactor has been measured with the miniature chamber WL-23292. For carrying out the measurements, it was buit a guide system that permit the insertion of the mini-chamber i between the fuel of the fuel elements. It can be introduced in two diferent positions a fuel element and in each it spans 26 axial positions. With this guide system the thermal neutron flux distribution of the IEA-R1 nuclear reactor can be obtained in a fast and efficient manner. The element measured flux distribution shows clearly the effects of control rods and reflectors in the IEA-R1 reactor. The difficulties encountered during the measurements are mentioned with detail as well as the procedures adopteed to overcome them. (Author) [pt

Measurement and simulation of thermal neutron flux distribution in the RTP core

Science.gov (United States)

Rabir, Mohamad Hairie B.; Jalal Bayar, Abi Muttaqin B.; Hamzah, Na'im Syauqi B.; Mustafa, Muhammad Khairul Ariff B.; Karim, Julia Bt. Abdul; Zin, Muhammad Rawi B. Mohamed; Ismail, Yahya B.; Hussain, Mohd Huzair B.; Mat Husin, Mat Zin B.; Dan, Roslan B. Md; Ismail, Ahmad Razali B.; Husain, Nurfazila Bt.; Jalil Khan, Zareen Khan B. Abdul; Yakin, Shaiful Rizaide B. Mohd; Saad, Mohamad Fauzi B.; Masood, Zarina Bt.

2018-01-01

The in-core thermal neutron flux distribution was determined using measurement and simulation methods for the Malaysian’s PUSPATI TRIGA Reactor (RTP). In this work, online thermal neutron flux measurement using Self Powered Neutron Detector (SPND) has been performed to verify and validate the computational methods for neutron flux calculation in RTP calculations. The experimental results were used as a validation to the calculations performed with Monte Carlo code MCNP. The detail in-core neutron flux distributions were estimated using MCNP mesh tally method. The neutron flux mapping obtained revealed the heterogeneous configuration of the core. Based on the measurement and simulation, the thermal flux profile peaked at the centre of the core and gradually decreased towards the outer side of the core. The results show a good agreement (relatively) between calculation and measurement where both show the same radial thermal flux profile inside the core: MCNP model over estimation with maximum discrepancy around 20% higher compared to SPND measurement. As our model also predicts well the neutron flux distribution in the core it can be used for the characterization of the full core, that is neutron flux and spectra calculation, dose rate calculations, reaction rate calculations, etc.

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

Tropical Gravity Wave Momentum Fluxes and Latent Heating Distributions

Science.gov (United States)

Geller, Marvin A.; Zhou, Tiehan; Love, Peter T.

2015-01-01

Recent satellite determinations of global distributions of absolute gravity wave (GW) momentum fluxes in the lower stratosphere show maxima over the summer subtropical continents and little evidence of GW momentum fluxes associated with the intertropical convergence zone (ITCZ). This seems to be at odds with parameterizations forGWmomentum fluxes, where the source is a function of latent heating rates, which are largest in the region of the ITCZ in terms of monthly averages. The authors have examined global distributions of atmospheric latent heating, cloud-top-pressure altitudes, and lower-stratosphere absolute GW momentum fluxes and have found that monthly averages of the lower-stratosphere GW momentum fluxes more closely resemble the monthly mean cloud-top altitudes rather than the monthly mean rates of latent heating. These regions of highest cloud-top altitudes occur when rates of latent heating are largest on the time scale of cloud growth. This, plus previously published studies, suggests that convective sources for stratospheric GW momentum fluxes, being a function of the rate of latent heating, will require either a climate model to correctly model this rate of latent heating or some ad hoc adjustments to account for shortcomings in a climate model's land-sea differences in convective latent heating.

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.

The measurements of thermal neutron flux distribution in a paraffin

Indian Academy of Sciences (India)

The term `thermal flux' implies a Maxwellian distribution of velocity and energy corresponding to the most probable velocity of 2200 ms-1 at 293.4 K. In order to measure the thermal neutron flux density, the foil activation method was used. Thermal neutron flux determination in paraffin phantom by counting the emitted rays of ...

Investigating the impact of uneven magnetic flux density distribution on core loss estimation

DEFF Research Database (Denmark)

Niroumand, Farideh Javidi; Nymand, Morten; Wang, Yiren

2017-01-01

is calculated according to an effective flux density value and the macroscopic dimensions of the cores. However, the flux distribution in the core can alter by core shapes and/or operating conditions due to nonlinear material properties. This paper studies the element-wise estimation of the loss in magnetic......There are several approaches for loss estimation in magnetic cores, and all these approaches highly rely on accurate information about flux density distribution in the cores. It is often assumed that the magnetic flux density evenly distributes throughout the core and the overall core loss...

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.

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...

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.

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.

Temporal expression-based analysis of metabolism.

Directory of Open Access Journals (Sweden)

Sara B Collins

Full Text Available Metabolic flux is frequently rerouted through cellular metabolism in response to dynamic changes in the intra- and extra-cellular environment. Capturing the mechanisms underlying these metabolic transitions in quantitative and predictive models is a prominent challenge in systems biology. Progress in this regard has been made by integrating high-throughput gene expression data into genome-scale stoichiometric models of metabolism. Here, we extend previous approaches to perform a Temporal Expression-based Analysis of Metabolism (TEAM. We apply TEAM to understanding the complex metabolic dynamics of the respiratorily versatile bacterium Shewanella oneidensis grown under aerobic, lactate-limited conditions. TEAM predicts temporal metabolic flux distributions using time-series gene expression data. Increased predictive power is achieved by supplementing these data with a large reference compendium of gene expression, which allows us to take into account the unique character of the distribution of expression of each individual gene. We further propose a straightforward method for studying the sensitivity of TEAM to changes in its fundamental free threshold parameter θ, and reveal that discrete zones of distinct metabolic behavior arise as this parameter is changed. By comparing the qualitative characteristics of these zones to additional experimental data, we are able to constrain the range of θ to a small, well-defined interval. In parallel, the sensitivity analysis reveals the inherently difficult nature of dynamic metabolic flux modeling: small errors early in the simulation propagate to relatively large changes later in the simulation. We expect that handling such "history-dependent" sensitivities will be a major challenge in the future development of dynamic metabolic-modeling techniques.

Population FBA predicts metabolic phenotypes in yeast.

Directory of Open Access Journals (Sweden)

Piyush Labhsetwar

2017-09-01

Full Text Available Using protein counts sampled from single cell proteomics distributions to constrain fluxes through a genome-scale model of metabolism, Population flux balance analysis (Population FBA successfully described metabolic heterogeneity in a population of independent Escherichia coli cells growing in a defined medium. We extend the methodology to account for correlations in protein expression arising from the co-regulation of genes and apply it to study the growth of independent Saccharomyces cerevisiae cells in two different growth media. We find the partitioning of flux between fermentation and respiration predicted by our model agrees with recent 13C fluxomics experiments, and that our model largely recovers the Crabtree effect (the experimentally known bias among certain yeast species toward fermentation with the production of ethanol even in the presence of oxygen, while FBA without proteomics constraints predicts respirative metabolism almost exclusively. The comparisons to the 13C study showed improvement upon inclusion of the correlations and motivated a technique to systematically identify inconsistent kinetic parameters in the literature. The minor secretion fluxes for glycerol and acetate are underestimated by our method, which indicate a need for further refinements to the metabolic model. For yeast cells grown in synthetic defined (SD medium, the calculated broad distribution of growth rates matches experimental observations from single cell studies, and we characterize several metabolic phenotypes within our modeled populations that make use of diverse pathways. Fast growing yeast cells are predicted to perform significant amount of respiration, use serine-glycine cycle and produce ethanol in mitochondria as opposed to slow growing cells. We use a genetic algorithm to determine the proteomics constraints necessary to reproduce the growth rate distributions seen experimentally. We find that a core set of 51 constraints are essential but

Enhancement of magnetic flux distribution in a DC superconducting electric motor

International Nuclear Information System (INIS)

Hamid, N A; Ewe, L S; Chin, K M

2013-01-01

Most motor designs require an air gap between the rotor and stator to enable the armature to rotate freely. The interaction of magnetic flux from rotor and stator within the air gap will provide the thrust for rotational motion. Thus, the understanding of magnetic flux in the vicinity of the air gap is very important to mathematically calculate the magnetic flux generated in the area. In this work, a finite element analysis was employed to study the behavior of the magnetic flux in view of designing a synchronous DC superconducting electric motor. The analysis provides an ideal magnetic flux distribution within the components of the motor. From the flux plot analysis, it indicates that flux losses are mainly in the forms of leakage and fringe effect. The analysis also shows that the flux density is high at the area around the air gap and the rotor. The high flux density will provide a high force area that enables the rotor to rotate. In contrast, the other parts of the motor body do not show high flux density indicating low distribution of flux. Consequently, a bench top model of a DC superconducting motor was developed where by motor with a 2-pole type winding was chosen. Each field coil was designed with a racetrack-shaped double pancake wound using DI-BSCCO Bi-2223 superconducting tapes. The performance and energy efficiency of the superconducting motor was superior when compared to the conventional motor with similar capacity.

Fast neutron fluxes distribution in Egyptian ilmenite concrete

International Nuclear Information System (INIS)

Megahed, R.M.; Abou El-Nasr, T.Z.; Bashter, I.I.

1978-01-01

This work is concerned with the study of the distribution of fast neutron fluxes in a new type of heavy concrete made from Egyptian ilmenite ores. The neutron source used was a collimated beam of reactor neutrons emitted from one of the horizontal channels of the ET-RR-1 reactor. Measurements were carried-out using phosphorous activation detectors. Iso-flux curves were represented which give directly the shape and thickness required to attenuate the emitted fast neutron flux to a certain value. The relaxation lengths were also evaluated from the measured data for both disc monodirectional source and infinite plane monodirectional source. The obtained values were compared with that calculated using the derived values of relative number densities and microscopic removal cross-sections of the different constituents. The obtained data show that ilmenite concrete attenuates fast neutron flux more strongly than ordinary concrete. A semiemperical formula was derived to calculate the fast neutron flux at different thicknesses along the beam axis. Another semiemperical formula was also derived to calculate the fast neutron flux in ordinary concrete along the beam axis using the corresponding value in ilmenite concrete

Flux distribution in single phase, Si-Fe, wound transformer cores

International Nuclear Information System (INIS)

Loizos, George; Kefalas, Themistoklis; Kladas, Antonios; Souflaris, Thanassis; Paparigas, Dimitris

2008-01-01

This paper shows experimental results of longitudinal flux density and its harmonics at the limb, the yoke and the corner as well as normal flux in the step lap joint of a single phase, Si-Fe, wound transformer core. Results show that the flux density as well as the harmonics content is higher in the inner (window) side of the core and reduces gradually towards the outer side. Variations of flux density distribution between the limb and the corner or the yoke of the core were observed. A full record of normal flux around the step lap region of the model core was also obtained. Longitudinal and normal flux findings will enable the development of more accurate numerical models that describe the magnetic behavior of magnetic cores

The effects of off-center pellets on the temperature distribution and the heat flux distribution of fuel rods in nuclear reactors

International Nuclear Information System (INIS)

Peng Muzhang; Xing Jianhua

1986-01-01

This paper analyzes the effects of off-center pellets on the steady state temperature distribution and heat flux distribution of fuel rods in the nuclear reactors, and derives the dimensionless temperature distribution relationships and the dimensionless heat flux distribution relationship from the fuel rods with off-center pellets. The calculated results show that the effects of off-center will result in not only deviations of the highest temperature placement in the fuel pellets, but also the circumferentially nonuniform distributions of the temperatures and heat fluxes of the fuel rod surfaces

THE X-RAY FLUX DISTRIBUTION OF SAGITTARIUS A* AS SEEN BY CHANDRA

International Nuclear Information System (INIS)

Neilsen, J.; Anton Pannekoek, University of Amsterdam, Postbus 94249, 1090 GE Amsterdam (Netherlands))" data-affiliation=" (Astronomical Institute, Anton Pannekoek, University of Amsterdam, Postbus 94249, 1090 GE Amsterdam (Netherlands))" >Markoff, S.; Nowak, M. A.; Baganoff, F. K.; Dexter, J.; Witzel, G.; Barrière, N.; Li, Y.; Degenaar, N.; Fragile, P. C.; Gammie, C.; Goldwurm, A.; Grosso, N.; Haggard, D.

2015-01-01

We present a statistical analysis of the X-ray flux distribution of Sgr A* from the Chandra X-Ray Observatory's 3 Ms Sgr A* X-ray Visionary Project in 2012. Our analysis indicates that the observed X-ray flux distribution can be decomposed into a steady quiescent component, represented by a Poisson process with rate Q = (5.24 ± 0.08) × 10 –3  counts s –1 , and a variable component, represented by a power law process (dN/dF∝F –ξ , ξ=1.92 −0.02 +0.03 ). This slope matches our recently reported distribution of flare luminosities. The variability may also be described by a log-normal process with a median unabsorbed 2-8 keV flux of 1.8 −0.6 +0.8 ×10 −14  erg s –1  cm –2 and a shape parameter σ = 2.4 ± 0.2, but the power law provides a superior description of the data. In this decomposition of the flux distribution, all of the intrinsic X-ray variability of Sgr A* (spanning at least three orders of magnitude in flux) can be attributed to flaring activity, likely in the inner accretion flow. We confirm that at the faint end, the variable component contributes ∼10% of the apparent quiescent flux, as previously indicated by our statistical analysis of X-ray flares in these Chandra observations. Our flux distribution provides a new and important observational constraint on theoretical models of Sgr A*, and we use simple radiation models to explore the extent to which a statistical comparison of the X-ray and infrared can provide insights into the physics of the X-ray emission mechanism

THE X-RAY FLUX DISTRIBUTION OF SAGITTARIUS A* AS SEEN BY CHANDRA

Energy Technology Data Exchange (ETDEWEB)

Neilsen, J. [Department of Astronomy, Boston University, Boston, MA 02215 (United States); Markoff, S. [Astronomical Institute, " Anton Pannekoek," University of Amsterdam, Postbus 94249, 1090 GE Amsterdam (Netherlands); Nowak, M. A.; Baganoff, F. K. [MIT Kavli Institute for Astrophysics and Space Research, Cambridge, MA 02139 (United States); Dexter, J. [Department of Astronomy, Hearst Field Annex, University of California, Berkeley, CA 94720-3411 (United States); Witzel, G. [Department of Physics and Astronomy, University of California, Los Angeles, CA 90095-1547 (United States); Barrière, N. [Space Sciences Laboratory, 7 Gauss Way, University of California, Berkeley, CA 94720-7450 (United States); Li, Y. [Department of Astronomy and Institute of Theoretical Physics and Astrophysics, Xiamen University, Xiamen, Fujian 361005 (China); Degenaar, N. [Institute of Astronomy, University of Cambridge, Cambridge, CB3 OHA (United Kingdom); Fragile, P. C. [Department of Physics and Astronomy, College of Charleston, Charleston, SC 29424 (United States); Gammie, C. [Department of Astronomy, University of Illinois Urbana-Champaign, 1002 West Green Street, Urbana, IL 61801 (United States); Goldwurm, A. [AstroParticule et Cosmologie (APC), Université Paris 7 Denis Diderot, F-75205 Paris cedex 13 (France); Grosso, N. [Observatoire Astronomique de Strasbourg, Université de Strasbourg, CNRS, UMR 7550, 11 rue de l' Université, F-67000 Strasbourg (France); Haggard, D., E-mail: jneilsen@space.mit.edu [Department of Physics and Astronomy, AC# 2244, Amherst College, Amherst, MA 01002 (United States)

2015-02-01

We present a statistical analysis of the X-ray flux distribution of Sgr A* from the Chandra X-Ray Observatory's 3 Ms Sgr A* X-ray Visionary Project in 2012. Our analysis indicates that the observed X-ray flux distribution can be decomposed into a steady quiescent component, represented by a Poisson process with rate Q = (5.24 ± 0.08) × 10{sup –3} counts s{sup –1}, and a variable component, represented by a power law process (dN/dF∝F {sup –ξ}, ξ=1.92{sub −0.02}{sup +0.03}). This slope matches our recently reported distribution of flare luminosities. The variability may also be described by a log-normal process with a median unabsorbed 2-8 keV flux of 1.8{sub −0.6}{sup +0.8}×10{sup −14} erg s{sup –1} cm{sup –2} and a shape parameter σ = 2.4 ± 0.2, but the power law provides a superior description of the data. In this decomposition of the flux distribution, all of the intrinsic X-ray variability of Sgr A* (spanning at least three orders of magnitude in flux) can be attributed to flaring activity, likely in the inner accretion flow. We confirm that at the faint end, the variable component contributes ∼10% of the apparent quiescent flux, as previously indicated by our statistical analysis of X-ray flares in these Chandra observations. Our flux distribution provides a new and important observational constraint on theoretical models of Sgr A*, and we use simple radiation models to explore the extent to which a statistical comparison of the X-ray and infrared can provide insights into the physics of the X-ray emission mechanism.

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

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.

3-D flux distribution and criticality calculation of TRIGA Mark-II

International Nuclear Information System (INIS)

Can, B.

1982-01-01

In this work, the static calculation of the (I.T.U. TRIGA Mark-II) flux distribution has been made. The three dimensional, r-θ-z, representation of the core has been used. In this representation, for different configuration, the flux distribution has been calculated depending on two group theory. The thermal-hydraulics, the poisoning effects have been ignored. The calculations have been made by using the three dimensional and multigroup code CAN. (author)

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.

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.

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.

Multilevel power distribution synthesis for a movable flux mapping system

International Nuclear Information System (INIS)

Bollacasa, D.; Terney, W.B.; Vincent, G.F.; Dziadosz, D.; Schleicher, T.

1992-01-01

A Computer Software package has been developed to support the synthesis of the 3-dimensional power distribution from detector signals from a movable flux mapping system. The power distribution synthesis is based on methodology developed for fixed incore detectors. The full core solution effectively couples all assemblies in the core whether they are instrumented or not. The solution is not subject to approximations for the treatment of assemblies where a measurement cannot be made and provides an accurate representation of axial variations which may be induced by axial blankets, burnable absorber cut back regions and axially zoned flux suppression rods

Metabolic fuels: regulating fluxes to select mix.

Science.gov (United States)

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.

Calculation of flux density distribution on irradiation field of electron accelerator

International Nuclear Information System (INIS)

Tanaka, Ryuichi

1977-03-01

The simple equation of flux density distribution in the irradiation field of an ordinary electron accelerator is a function of the physical parameters concerning electron irradiation. Calculation is based on the mean square scattering angle derived from a simple multiple scattering theory, with the correction factors of air scattering, beam scanning and number transmission coefficient. The flux density distribution was measured by charge absorption in a graphite target set in the air. For the calculated mean square scattering angles of 0.089-0.29, the values of calculation agree with those by experiment within about 10% except at large scattering angles. The method is applicable to dose evaluation of ordinary electron accelerators and design of various irradiators for radiation chemical reaction. Applicability of the simple multiple scattering theory in calculation of the scattered flux density and periodical variation of the flux density of scanning beam are also described. (auth.)

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.

Inferring metabolic states in uncharacterized environments using gene-expression measurements.

Directory of Open Access Journals (Sweden)

Sergio Rossell

Full Text Available The large size of metabolic networks entails an overwhelming multiplicity in the possible steady-state flux distributions that are compatible with stoichiometric constraints. This space of possibilities is largest in the frequent situation where the nutrients available to the cells are unknown. These two factors: network size and lack of knowledge of nutrient availability, challenge the identification of the actual metabolic state of living cells among the myriad possibilities. Here we address this challenge by developing a method that integrates gene-expression measurements with genome-scale models of metabolism as a means of inferring metabolic states. Our method explores the space of alternative flux distributions that maximize the agreement between gene expression and metabolic fluxes, and thereby identifies reactions that are likely to be active in the culture from which the gene-expression measurements were taken. These active reactions are used to build environment-specific metabolic models and to predict actual metabolic states. We applied our method to model the metabolic states of Saccharomyces cerevisiae growing in rich media supplemented with either glucose or ethanol as the main energy source. The resulting models comprise about 50% of the reactions in the original model, and predict environment-specific essential genes with high sensitivity. By minimizing the sum of fluxes while forcing our predicted active reactions to carry flux, we predicted the metabolic states of these yeast cultures that are in large agreement with what is known about yeast physiology. Most notably, our method predicts the Crabtree effect in yeast cells growing in excess glucose, a long-known phenomenon that could not have been predicted by traditional constraint-based modeling approaches. Our method is of immediate practical relevance for medical and industrial applications, such as the identification of novel drug targets, and the development of

Framework for network modularization and Bayesian network analysis to investigate the perturbed metabolic network

Directory of Open Access Journals (Sweden)

Kim Hyun

2011-12-01

Full Text Available Abstract Background Genome-scale metabolic network models have contributed to elucidating biological phenomena, and predicting gene targets to engineer for biotechnological applications. With their increasing importance, their precise network characterization has also been crucial for better understanding of the cellular physiology. Results We herein introduce a framework for network modularization and Bayesian network analysis (FMB to investigate organism’s metabolism under perturbation. FMB reveals direction of influences among metabolic modules, in which reactions with similar or positively correlated flux variation patterns are clustered, in response to specific perturbation using metabolic flux data. With metabolic flux data calculated by constraints-based flux analysis under both control and perturbation conditions, FMB, in essence, reveals the effects of specific perturbations on the biological system through network modularization and Bayesian network analysis at metabolic modular level. As a demonstration, this framework was applied to the genetically perturbed Escherichia coli metabolism, which is a lpdA gene knockout mutant, using its genome-scale metabolic network model. Conclusions After all, it provides alternative scenarios of metabolic flux distributions in response to the perturbation, which are complementary to the data obtained from conventionally available genome-wide high-throughput techniques or metabolic flux analysis.

Framework for network modularization and Bayesian network analysis to investigate the perturbed metabolic network.

Science.gov (United States)

Kim, Hyun Uk; Kim, Tae Yong; Lee, Sang Yup

2011-01-01

Genome-scale metabolic network models have contributed to elucidating biological phenomena, and predicting gene targets to engineer for biotechnological applications. With their increasing importance, their precise network characterization has also been crucial for better understanding of the cellular physiology. We herein introduce a framework for network modularization and Bayesian network analysis (FMB) to investigate organism's metabolism under perturbation. FMB reveals direction of influences among metabolic modules, in which reactions with similar or positively correlated flux variation patterns are clustered, in response to specific perturbation using metabolic flux data. With metabolic flux data calculated by constraints-based flux analysis under both control and perturbation conditions, FMB, in essence, reveals the effects of specific perturbations on the biological system through network modularization and Bayesian network analysis at metabolic modular level. As a demonstration, this framework was applied to the genetically perturbed Escherichia coli metabolism, which is a lpdA gene knockout mutant, using its genome-scale metabolic network model. After all, it provides alternative scenarios of metabolic flux distributions in response to the perturbation, which are complementary to the data obtained from conventionally available genome-wide high-throughput techniques or metabolic flux analysis.

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

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...

INDIAN POINT REACTOR REACTIVITY AND FLUX DISTRIBUTION MEASUREMENTS

Energy Technology Data Exchange (ETDEWEB)

Batch, M. L.; Fischer, F. E.

1963-11-15

The reactivity of the Indian Point core was measured near zero reactivity at various shim and control rod patterns. Flux distribution measurements were also made, and the results are expressed in terms of power peaking factors and normalized detector response during rod withdrawal. (D.L.C.)

Poloidal and toroidal heat flux distribution in the CCT tokamak

International Nuclear Information System (INIS)

Brown, M.L.; Dhir, V.K.; Taylor, R.J.

1990-01-01

Plasma heat flux to the Faraday shield panels of the UCLA Continuous Current Tokamak (CCT) has been measured calorimetrically in order to identify the dominant parameters affecting the spatial distribution of heat deposition. Three heating methods were investigated: audio frequency discharge cleaning, RF heating, and AC ohmic. Significant poloidal asymmetry is present in the heat flux distribution. On the average, the outer panels received 25-30% greater heat flux than the inner ones, with the ratio of maximum to minimum values attaining a difference of more than a factor of 2. As a diagnostic experiment the current to a selected toroidal field coil was reduced in order to locally deflect the toroidal field lines outward in a ripple-like fashion. Greatly enhanced heat deposition (up to a factor of 4) was observed at this location on the outside Faraday panels. The enhancement was greatest for conditions of low toroidal field and low neutral pressure, leading to low plasma densities, for which Coulomb collisions are the smallest. An exponential model based on a heat flux e-folding length describes the experimentally found localization of thermal energy quite adequately. (orig.)

A diffusion-theoretical method to calculate the neutron flux distribution in multisphere configurations

International Nuclear Information System (INIS)

Schuerrer, F.

1980-01-01

For characterizing heterogene configurations of pebble-bed reactors the fine structure of the flux distribution as well as the determination of the macroscopic neutronphysical quantities are of interest. When calculating system parameters of Wigner-Seitz-cells the usual codes for neutron spectra calculation always neglect the modulation of the neutron flux by the influence of neighbouring spheres. To judge the error arising from that procedure it is necessary to determinate the flux distribution in the surrounding of a spherical fuel element. In the present paper an approximation method to calculate the flux distribution in the two-sphere model is developed. This method is based on the exactly solvable problem of the flux determination of a point source of neutrons in an infinite medium, which contains a spherical perturbation zone eccentric to the point source. An iteration method allows by superposing secondary fields and alternately satisfying the conditions of continuity on the surface of each of the two fuel elements to advance to continually improving approximations. (orig.) 891 RW/orig. 892 CKA [de

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

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.

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.

The flow distribution in the parallel tubes of the cavity receiver under variable heat flux

International Nuclear Information System (INIS)

Hao, Yun; Wang, Yueshe; Hu, Tian

2016-01-01

Highlights: • An experimental loop is built to find the flow distribution in the parallel tubes. • With the concentration of heat flux, two-phase flow makes distribution more uneven. • The total flow rate is chosen appropriately for a wider heat flux distribution. • A suitable system pressure is essential for the optimization of flow distribution. - Abstract: As an optical component of tower solar thermal power station, the heliostat mirror reflects sunlight to one point of the heated surface in the solar cavity receiver, called as one-point focusing system. The radiation heat flux concentrated in the cavity receiver is always non-uniform temporally and spatially, which may lead to extremely local over-heat on the receiver evaporation panels. In this paper, an electrical heated evaporating experimental loop, including five parallel vertical tubes, is set up to evaluate the hydrodynamic characteristics of evaporation panels in a solar cavity receiver under various non-uniform heat flux. The influence of the heat flux concentration ratio, total flow rate, and system pressure on the flow distribution of parallel tubes is discussed. It is found that the flow distribution becomes significantly worse with the increase of heat flux and concentration ratio; and as the system pressure decreased, the flow distribution is improved. It is extremely important to obtain these interesting findings for the safe and stable operation of solar cavity receiver, and can also provide valuable references for the design and optimization of operating parameters solar tower power station system.

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...

A method to calculate flux distribution in reactor systems containing materials with grain structure

International Nuclear Information System (INIS)

Stepanek, J.

1980-01-01

A method is proposed to compute the neutron flux spatial distribution in slab, spherical or cylindrical systems containing zones with close grain structure of material. Several different types of equally distributed particles embedded in the matrix material are allowed in one or more zones. The multi-energy group structure of the flux is considered. The collision probability method is used to compute the fluxes in the grains and in an ''effective'' part of the matrix material. Then the overall structure of the flux distribution in the zones with homogenized materials is determined using the DPN ''surface flux'' method. Both computations are connected using the balance equation during the outer iterations. The proposed method is written in the code SURCU-DH. Two testcases are computed and discussed. One testcase is the computation of the eigenvalue in simplified slab geometry of an LWR container of one zone with boral grains equally distributed in an aluminium matrix. The second is the computation of the eigenvalue in spherical geometry of the HTR pebble-bed cell with spherical particles embedded in a graphite matrix. The results are compared to those obtained by repeated use of the WIMS Code. (author)

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.

Inverse identification of intensity distributions from multiple flux maps in concentrating solar applications

International Nuclear Information System (INIS)

Erickson, Ben; Petrasch, Jörg

2012-01-01

Radiative flux measurements at the focal plane of solar concentrators are typically performed using digital cameras in conjunction with Lambertian targets. To accurately predict flux distributions on arbitrary receiver geometries directional information about the radiation is required. Currently, the directional characteristics of solar concentrating systems are predicted via ray tracing simulations. No direct experimental technique to determine intensities of concentrating solar systems is available. In the current paper, multiple parallel flux measurements at varying distances from the focal plane together with a linear inverse method and Tikhonov regularization are used to identify the directional and spatial intensity distribution at the solution plane. The directional binning feature of an in-house Monte Carlo ray tracing program is used to provide a reference solution. The method has been successfully applied to two-dimensional concentrators, namely parabolic troughs and elliptical troughs using forward Monte Carlo ray tracing simulations that provide the flux maps as well as consistent, associated intensity distribution for validation. In the two-dimensional case, intensity distributions obtained from the inverse method approach the Monte Carlo forward solution. In contrast, the method has not been successful for three dimensional and circular symmetric concentrator geometries.

Flux distribution measurements in the Bruce A unit 1 reactor

International Nuclear Information System (INIS)

Okazaki, A.; Kettner, D.A.; Mohindra, V.K.

1977-07-01

Flux distribution measurements were made by copper wire activation during low power commissioning of the unit 1 reactor of the Bruce A generating station. The distribution was measured along one diameter near the axial and horizontal midplanes of the reactor core. The activity distribution along the copper wire was measured by wire scanners with NaI detectors. The experiments were made for five configurations of reactivity control mechanisms. (author)

The role of metabolic engineering in the production of secondary metabolites

DEFF Research Database (Denmark)

Nielsen, Jens Bredal

1998-01-01

In the production of secondary metabolites yield and productivity are the most important design parameters. The focus is therefore to direct the carbon fluxes towards the product of interest, and this can be obtained through metabolic engineering whereby directed genetic changes are introduced...... into the production strain. In this process it is, however, important to analyze the metabolic network through measurement of the intracellular metabolites and the flux distributions. Besides playing an important role in the optimization of existing processes, metabolic engineering also offers the possibility...

An analytical transport theory method for calculating flux distribution in slab cells

International Nuclear Information System (INIS)

Abdel Krim, M.S.

2001-01-01

A transport theory method for calculating flux distributions in slab fuel cell is described. Two coupled integral equations for flux in fuel and moderator are obtained; assuming partial reflection at moderator external boundaries. Galerkin technique is used to solve these equations. Numerical results for average fluxes in fuel and moderator and the disadvantage factor are given. Comparison with exact numerical methods, that is for total reflection moderator outer boundaries, show that the Galerkin technique gives accurate results for the disadvantage factor and average fluxes. (orig.)

Critical sizes and flux distributions in the shut down pile; Tailles critiques et cartes de flux a froid

Energy Technology Data Exchange (ETDEWEB)

Banchereau, A; Berthier, P; Genthon, J P; Gourdon, C; Lattes, R; Martelly, J; Mazancourt, R de; Portes, L; Sagot, M; Schmitt, A P; Tanguy, P; Teste du Bailler, A; Veyssiere, A [Commissariat a l' Energie Atomique, Saclay (France). Centre d' Etudes Nucleaires

1957-07-01

An important part of the experiments carried out on the reactor G1 during a period of shut-down has consisted in determinations of critical sizes, and measurements of flux distribution by irradiations of detectors. This report deals with the following points: 1- Critical sizes of the flat pile, the long pile and the uranium-thorium pile. 2- Flux charts of the same piles, and study of an exponential experiment. 3- Determination of the slit effect. 4- Calculation of the anisotropy of the lattice. 5- Description of the experimental apparatus of the irradiation measurements. (author) [French] Une part importante des experiences a froid effectuees sur le reacteur G1 a consiste en des determinations de tailles critiques et des mesures de distributions de flux par irradiations de detecteurs. Le present rapport traite les points suivants: 1- Tailles critiques de la pile plate, de la pile longue, de la pile a uranium-thorium. 2 - Cartes de flux des memes piles et etude d'une experience exponentielle. 3 - Determination de l'effet de fente. 4 - Calcul de l'anisotropie du reseau. 5 - Description de l'appareillage experimental des mesures d'irradiations. (auteur)

Critical sizes and flux distributions in the shut down pile; Tailles critiques et cartes de flux a froid

Energy Technology Data Exchange (ETDEWEB)

Banchereau, A.; Berthier, P.; Genthon, J.P.; Gourdon, C.; Lattes, R.; Martelly, J.; Mazancourt, R. de; Portes, L.; Sagot, M.; Schmitt, A.P.; Tanguy, P.; Teste du Bailler, A.; Veyssiere, A. [Commissariat a l' Energie Atomique, Saclay (France). Centre d' Etudes Nucleaires

1957-07-01

An important part of the experiments carried out on the reactor G1 during a period of shut-down has consisted in determinations of critical sizes, and measurements of flux distribution by irradiations of detectors. This report deals with the following points: 1- Critical sizes of the flat pile, the long pile and the uranium-thorium pile. 2- Flux charts of the same piles, and study of an exponential experiment. 3- Determination of the slit effect. 4- Calculation of the anisotropy of the lattice. 5- Description of the experimental apparatus of the irradiation measurements. (author) [French] Une part importante des experiences a froid effectuees sur le reacteur G1 a consiste en des determinations de tailles critiques et des mesures de distributions de flux par irradiations de detecteurs. Le present rapport traite les points suivants: 1- Tailles critiques de la pile plate, de la pile longue, de la pile a uranium-thorium. 2 - Cartes de flux des memes piles et etude d'une experience exponentielle. 3 - Determination de l'effet de fente. 4 - Calcul de l'anisotropie du reseau. 5 - Description de l'appareillage experimental des mesures d'irradiations. (auteur)

Surface flux density distribution characteristics of bulk high-T c superconductor in external magnetic field

International Nuclear Information System (INIS)

Nishikawa, H.; Torii, S.; Yuasa, K.

2005-01-01

This paper describes the measured results of the two-dimensional flux density distribution of a YBCO bulk under applied AC magnetic fields with various frequency. Melt-processed oxide superconductors have been developed in order to obtain strong pinning forces. Various electric mechanical systems or magnetic levitation systems use those superconductors. The major problem is that cracks occur because the bulk superconductors are brittle. The bulk may break in magnetizing process after cracks make superconducting state instable. The trapped flux density and the permanent current characteristics of bulk superconductors have been analyzed, so as to examine the magnetizing processes or superconducting states of the bulk. In those studies, the two-dimensional surface flux density distributions of the bulk in static fields are discussed. On the other hand, the distributions in dynamic fields are little discussed. We attempted to examine the states of the bulk in the dynamic fields, and made a unique experimental device which has movable sensors synchronized with AC applied fields. As a result, the two-dimensional distributions in the dynamic fields are acquired by recombining the one-dimensional distributions. The dynamic states of the flux of the bulk and the influences of directions of cracks are observed from the distributions. In addition, a new method for measuring two-dimensional flux density distribution under dynamic magnetic fields is suggested

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.

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

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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.

The effect of an iron plug on the neutron flux distributions in water

International Nuclear Information System (INIS)

Lotfi, A.; Maayouf, R.M.A.; Megahid, R.

1978-01-01

This work is concerned with studying both fast and thermal neutron fluxes distribution in water and its perturbation due to the presence of a cylindrical iron plug. The measurements were carried out using a collimated neutron beam emitted from one of the horizontal channels of the ET-RR-1 reactor. The fast neutron fluxes were measured using phosphorus activation detectors, while the thermal neutron ones were measured using fission fragment track detectors from glass. The results show that the presence of an iron plug causes a remarkable change in the intensities of both the fast and thermal neutron fluxes distribution in the water medium surrounding the iron plug. The flux intensities at the peaks, formed beyond the iron plug in case of thermal neutrons, are also compared with values calculated using the available emperical formula

(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.

Surface flux density distribution characteristics of bulk high-Tc superconductor in external magnetic field

International Nuclear Information System (INIS)

Torii, S.; Yuasa, K.

2004-01-01

Various magnetic levitation systems using oxide superconductors are developed as strong pinning forces are obtained in melt-processed bulk. However, the trapped flux of superconductor is moved by flux creep and fluctuating magnetic field. Therefore, to examine the internal condition of superconductor, the authors measure the dynamic surface flux density distribution of YBCO bulk. Flux density measurement system has a structure with the air-core coil and the Hall sensors. Ten Hall sensors are arranged in series. The YBCO bulk, which has 25 mm diameter and 13 mm thickness, is field cooled by liquid nitrogen. After that, magnetic field is changed by the air-core coil. This paper describes about the measured results of flux density distribution of YBCO bulk in the various frequencies of air-core coils currents

Surface flux density distribution characteristics of bulk high- Tc superconductor in external magnetic field

Science.gov (United States)

Torii, S.; Yuasa, K.

2004-10-01

Various magnetic levitation systems using oxide superconductors are developed as strong pinning forces are obtained in melt-processed bulk. However, the trapped flux of superconductor is moved by flux creep and fluctuating magnetic field. Therefore, to examine the internal condition of superconductor, the authors measure the dynamic surface flux density distribution of YBCO bulk. Flux density measurement system has a structure with the air-core coil and the Hall sensors. Ten Hall sensors are arranged in series. The YBCO bulk, which has 25 mm diameter and 13 mm thickness, is field cooled by liquid nitrogen. After that, magnetic field is changed by the air-core coil. This paper describes about the measured results of flux density distribution of YBCO bulk in the various frequencies of air-core coils currents.

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

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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.

Pathway confirmation and flux analysis of central metabolic pathways in Desulfovibrio vulgaris Hildenborough using Gas Chromatography-Mass Spectrometry and Fourier Transform-Ion Cyclotron Resonance Mass Spectrometry

International Nuclear Information System (INIS)

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

2007-01-01

Flux distribution in central metabolic pathways of Desulfovibrio vulgaris Hildenborough was examined using 13C tracer experiments. Consistent with the current genome annotation and independent evidence from enzyme activity assays, the isotopomer results from both GC-MS and Fourier Transform-Ion Cyclotron Resonance mass spectrometry (FT-ICR MS) indicate the lack of oxidatively functional TCA cycle and an incomplete pentose phosphate pathway. Results from this study suggest that fluxes through both pathways are limited to biosynthesis. The data also indicate that >80 percent of the lactate was converted to acetate and the reactions involved are the primary route of energy production (NAD(P)H and ATP production). Independent of the TCA cycle, direct cleavage of acetyl-CoA to CO and 5,10-methyl-THF also leads to production of NADH and ATP. Although the genome annotation implicates a ferredoxin-dependent oxoglutarate synthase, isotopic evidence does not support flux through this reaction in either the oxidative or reductive mode; therefore, the TCA cycle is incomplete. FT-ICR MS was used to locate the labeled carbon distribution in aspartate and glutamate and confirmed the presence of an atypical enzyme for citrate formation suggested in previous reports (the citrate synthesized by this enzyme is the isotopic antipode of the citrate synthesized by the (S)-citrate synthase). These findings enable a better understanding of the relation between genome annotation and actual metabolic pathways in D. vulgaris, and also demonstrate FT-ICR MS as a powerful tool for isotopomer analysis, overcoming problems in both GC-MS and NMR spectroscopy

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]).

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.

YANA – a software tool for analyzing flux modes, gene-expression and enzyme activities

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Engels Bernd

2005-06-01

Full Text Available Abstract Background A number of algorithms for steady state analysis of metabolic networks have been developed over the years. Of these, Elementary Mode Analysis (EMA has proven especially useful. Despite its low user-friendliness, METATOOL as a reliable high-performance implementation of the algorithm has been the instrument of choice up to now. As reported here, the analysis of metabolic networks has been improved by an editor and analyzer of metabolic flux modes. Analysis routines for expression levels and the most central, well connected metabolites and their metabolic connections are of particular interest. Results YANA features a platform-independent, dedicated toolbox for metabolic networks with a graphical user interface to calculate (integrating METATOOL, edit (including support for the SBML format, visualize, centralize, and compare elementary flux modes. Further, YANA calculates expected flux distributions for a given Elementary Mode (EM activity pattern and vice versa. Moreover, a dissection algorithm, a centralization algorithm, and an average diameter routine can be used to simplify and analyze complex networks. Proteomics or gene expression data give a rough indication of some individual enzyme activities, whereas the complete flux distribution in the network is often not known. As such data are noisy, YANA features a fast evolutionary algorithm (EA for the prediction of EM activities with minimum error, including alerts for inconsistent experimental data. We offer the possibility to include further known constraints (e.g. growth constraints in the EA calculation process. The redox metabolism around glutathione reductase serves as an illustration example. All software and documentation are available for download at http://yana.bioapps.biozentrum.uni-wuerzburg.de. Conclusion A graphical toolbox and an editor for METATOOL as well as a series of additional routines for metabolic network analyses constitute a new user

Distribution and metabolism of quaternary amines in salt marshes

Science.gov (United States)

King, Gary M.

1985-01-01

Quaternary amines such as glycine betaine (GBT) are common osmotically active solutes in much of the marine biota. GBT is accumulated by various bacteria, algae, higher plants, invertebrates, and vertebrates in response to salinity or water stresses; in some species, GBT occurs at tens to hundreds of millimolar concentrations and can account for a significant fraction of total nitrogen. Initial studies suggest that GBT is readily converted to two potential methane precursors, trimethylamine (TMA) and acetate, in anoxic sediments. TMA is apparently the most important methane precursor in surface sediments containing sulfate reducing bacteria. In salt marshes, the bulk of the methane formed may be due to the metabolism of TMA rather than other substrates. Current research is focussed on testing this hypothesis and on determining the role of quaternary amino osmoregulatory solutes in methane fluxes from marine environments. Preliminary studies have dealt with several problems: (1) determination of GBT concentrations in the dominant flora and fauna of salt marshes; (2) synthesis of radiolabelled GBT for metabolic studies; and (3) determination of fates of BGT in marine sediments using radiotracers. Both GC and HPLC techniques have been used to assay GBT concentrations in plant and animal tissues. S. alterniflora is probably the only significant source of GBT (and indirectly of methane) since the biomass and distribution of most other species is limited. Current estimates suggest that S. alterniflora GBT could account for most of the methane efflux from salt marshes.

Flux distribution measurements in the Bruce B Unit 6 reactor using a transportable traveling flux detector system

International Nuclear Information System (INIS)

Leung, T.C.; Drewell, N.H.; Hall, D.S.; Lopez, A.M.

1987-01-01

A transportable traveling flux detector (TFD) system for use in power reactors has been developed and tested at Chalk River Nuclear Labs. in Canada. It consists of a miniature fission chamber, a motor drive mechanism, a computerized control unit, and a data acquisition subsystem. The TFD system was initially designed for the in situ calibration of fixed self-powered detectors in operating power reactors and for flux measurements to verify reactor physics calculations. However, this system can also be used as a general diagnostic tool for the investigation of apparent detector failures and flux anomalies and to determine the movement of reactor internal components. This paper describes the first successful use of the computerized TFD system in an operating Canada deuterium uranium (CANDU) power reactor and the results obtained from the flux distribution measurements. An attempt is made to correlate minima in the flux profile with the locations of fuel channels so that future measurements can be used to determine the sag of the channels. Twenty-seven in-core flux detector assemblies in the 855-MW (electric) Unit 6 reactor of the Ontario Hydro Bruce B Generating Station were scanned

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.

Implementation of drift-flux correlations in ARTIST and its assessment in comparison with THETIS void distribution

International Nuclear Information System (INIS)

Yun, B. J.; Kim, H. C.; Moon, S. K.; Lee, W. J.

1998-01-01

Non-homogeneous, non-equilibrium drift-flux model was developed in ARTIST code to enhance capability of predicting two-phase flow void distribution at low pressure and low flow conditions. The governing equations of ARTIST code consist of three continuity equations (mixture, liquid, and noncondensibles), two energy equations (gas and mixture) and one mixture momentum equation constituted with the drift-flux model. In order to provide the Co and the Vgj of drift-flux model, four drift-flux correlations, which are Chexal-Lellouche, Ohkawa-Lahey, GE Ramp and Dix models, are implemented. In order to evaluate the accuracy of the drift flux correlations, the steady state void distributions of the THETIS boil-off tests are simulated. The results show that the drift-flux model is quite satisfactory in terms of accuracy and computational efficiency. Among the four drift-flux correlations, the Chexal-Lellouche model showed wide applicability in the prediction of void fraction from low to high pressure condition. Especially, the axial void distribution at low pressure and low flow is far better than those of both the two-fluid model of RELAP5/MOD3 code and the homogeneous model. Thus, the drift-flux model of the ARTIST code can be used as an efficient tool in predicting the void distribution of two-phase flow at low pressure and low flow conditions

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.

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

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

Neutron Flux Distribution on Neutron Radiography Facility After Fixing the Collimator

International Nuclear Information System (INIS)

Supandi; Parikin; Mohtar; Sunardi; Roestam, S

1996-01-01

The Radiography Neutron Facility consists of an inner collimator, outer collimator, main shutter, second shutter and the sample chamber with 300 mm in diameter. Neutron beam quality depends on the neutron flux intensities distribution, L/D ratio Cd ratio, neutron/gamma ratio. The results show that the neutron flux intensity was 2.83 x 107 n cm-2.s-1, with deviation of + 7.8 % and it was distributed homogeneously at the sample position of 200 mm diameter. The beam characteristics were L/D ratio 98 and Rod 8, and neutron gamma ratio 3.08 x 105n.cm-2.mR-1 and Reactor Power was 20 MW. This technique can be used to examine sample with diameter of < 200 mm

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.

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.

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...

Bringing metabolic networks to life: integration of kinetic, metabolic, and proteomic data

Directory of Open Access Journals (Sweden)

Klipp Edda

2006-12-01

Full Text Available Abstract Background Translating a known metabolic network into a dynamic model requires reasonable guesses of all enzyme parameters. In Bayesian parameter estimation, model parameters are described by a posterior probability distribution, which scores the potential parameter sets, showing how well each of them agrees with the data and with the prior assumptions made. Results We compute posterior distributions of kinetic parameters within a Bayesian framework, based on integration of kinetic, thermodynamic, metabolic, and proteomic data. The structure of the metabolic system (i.e., stoichiometries and enzyme regulation needs to be known, and the reactions are modelled by convenience kinetics with thermodynamically independent parameters. The parameter posterior is computed in two separate steps: a first posterior summarises the available data on enzyme kinetic parameters; an improved second posterior is obtained by integrating metabolic fluxes, concentrations, and enzyme concentrations for one or more steady states. The data can be heterogenous, incomplete, and uncertain, and the posterior is approximated by a multivariate log-normal distribution. We apply the method to a model of the threonine synthesis pathway: the integration of metabolic data has little effect on the marginal posterior distributions of individual model parameters. Nevertheless, it leads to strong correlations between the parameters in the joint posterior distribution, which greatly improve the model predictions by the following Monte-Carlo simulations. Conclusion We present a standardised method to translate metabolic networks into dynamic models. To determine the model parameters, evidence from various experimental data is combined and weighted using Bayesian parameter estimation. The resulting posterior parameter distribution describes a statistical ensemble of parameter sets; the parameter variances and correlations can account for missing knowledge, measurement

Rocket measurements of relativistic electrons: New features in fluxes, spectra and pitch angle distributions

International Nuclear Information System (INIS)

Herrero, F.A.; Baker, D.N.; Goldberg, R.A.

1991-01-01

The authors report new features of precipitating relativistic electron fluxes measured on a spinning sounding rocket payload at midday between altitudes of 70 and 130 km in the auroral region (Poker Flat, Alaska, 65.1 degree N, 147.5 degree W, and L = 5.5). The sounding rocket (NASA 33.059) was launched at 21:29 UT on May 13, 1990 during a relativistic electron enhancement event of modest intensity. Electron fluxes were measured for a total of about 210 seconds at energies from 0.1 to 3.8 MeV, while pitch angle was sampled from 0 degree to 90 degree every spin cycle. Flux levels during the initial 90 seconds were about 5 to 8 times higher than in the next 120 seconds, revealing a time scale of more than 100 seconds for large amplitude intensity variations. A shorter time scale appeared for downward electron bursts lasting 10 to 20 seconds. Electrons with energies below about 0.2 MeV showed isotropic pitch angle distributions during most of the first 90 seconds of data, while at higher energies the electrons had highest fluxes near the mirroring angle (90 degree); when they occurred, the noted downward bursts were seen at all energies. Data obtained during the second half of the flight showed little variation in the shape of the pitch angle distribution for energies greater than 0.5 MeV; the flux at 90 degree was about 100 times the flux at 0 degree. They have compared the low altitude fluxes with those measured at geostationary orbit (L = 6.6), and find that the low altitude fluxes are much higher than expected from a simple mapping of a pancake distribution at high altitudes (at the equator). Energy deposition of this modest event is estimated to increase rapidly above 45 km, already exceeding the cosmic ray background at 45 km

Critical sizes and flux distributions in the shut down pile

International Nuclear Information System (INIS)

Banchereau, A.; Berthier, P.; Genthon, J.P.; Gourdon, C.; Lattes, R.; Martelly, J.; Mazancourt, R. de; Portes, L.; Sagot, M.; Schmitt, A.P.; Tanguy, P.; Teste du Bailler, A.; Veyssiere, A.

1957-01-01

An important part of the experiments carried out on the reactor G1 during a period of shut-down has consisted in determinations of critical sizes, and measurements of flux distribution by irradiations of detectors. This report deals with the following points: 1- Critical sizes of the flat pile, the long pile and the uranium-thorium pile. 2- Flux charts of the same piles, and study of an exponential experiment. 3- Determination of the slit effect. 4- Calculation of the anisotropy of the lattice. 5- Description of the experimental apparatus of the irradiation measurements. (author) [fr

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.

Enhancing sesquiterpene production in Saccharomyces cerevisiae through in silico driven metabolic engineering

DEFF Research Database (Denmark)

Asadollahi, Mohammadali; Maury, Jerome; Patil, Kiran Raosaheb

2009-01-01

A genome-scale metabolic model was used to identify new target genes for enhanced biosynthesis of sesquiterpenes in the yeast Saccharomyces cerevisiae. The effect of gene deletions on the flux distributions in the metabolic model of S. cerevisiae was assessed using OptGene as the modeling framework...

Process and equipment for monitoring flux distribution in a nuclear reactor outside the core

International Nuclear Information System (INIS)

Graham, K.F.; Gopal, R.

1977-01-01

This concerns the monitoring system for axial flux distribution during the whole load operating range lying outside the core of, for example, a PWR. Flux distribution cards can be produced continuously. The core is divided into at least three sections, which are formed by dividing it at right angles to the longitudinal axis, and the flux is measured outside the core using adjacent detectors. Their output signals are calibrated by amplifiers so that the load distribution in the associated sections is reproduced. A summation of the calibrated output signals and the formation of a mean load signal takes place in summing stages. For monitoring, this is compared with a value which corresponds to the maximum permissible load setting. Apart from this the position of the control rods in the core can be taken into account by multiplication of the mean load signals by suitable peak factors. The distribution of monitoring positions or the position of the detectors can be progressive or symmetrical along the axis. (DG) 891 HP [de

Proposal for a new method of reactor neutron flux distribution determination

Energy Technology Data Exchange (ETDEWEB)

Popic, V R [Institute of nuclear sciences Boris Kidric, Vinca, Beograd (Serbia and Montenegro)

1964-01-15

A method, based on the measurements of the activity produced in a medium flowing with variable velocity through a reactor, for the determination of the neutron flux distribution inside a reactor is considered theoretically (author)

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...

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...

Surface flux density distribution characteristics of bulk high-T{sub c} superconductor in external magnetic field

Energy Technology Data Exchange (ETDEWEB)

Torii, S.; Yuasa, K

2004-10-01

Various magnetic levitation systems using oxide superconductors are developed as strong pinning forces are obtained in melt-processed bulk. However, the trapped flux of superconductor is moved by flux creep and fluctuating magnetic field. Therefore, to examine the internal condition of superconductor, the authors measure the dynamic surface flux density distribution of YBCO bulk. Flux density measurement system has a structure with the air-core coil and the Hall sensors. Ten Hall sensors are arranged in series. The YBCO bulk, which has 25 mm diameter and 13 mm thickness, is field cooled by liquid nitrogen. After that, magnetic field is changed by the air-core coil. This paper describes about the measured results of flux density distribution of YBCO bulk in the various frequencies of air-core coils currents.

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

Science.gov (United States)

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.

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

Directory of Open Access Journals (Sweden)

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.

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

Directory of Open Access Journals (Sweden)

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.

Optimization of neutron flux distribution in Isotope Production Reactor

International Nuclear Information System (INIS)

Valladares, G.L.

1988-01-01

In order to optimize the thermal neutrons flux distribution in a Radioisotope Production and Research Reactor, the influence of two reactor parameters was studied, namely the Vmod / Vcomb ratio and the core volume. The reactor core is built with uranium oxide pellets (UO 2 ) mounted in rod clusters, with an enrichment level of ∼3 %, similar to LIGHT WATER POWER REATOR (LWR) fuel elements. (author) [pt

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

Conical pitch angle distributions of very-low energy ion fluxes observed by ISEE 1

International Nuclear Information System (INIS)

Horowitz, J.L.; Baugher, C.R.; Chappell, C.R.; Shelley, E.G.; Young, D.T.

1982-01-01

Observations of low-energy ionospheric ions by the plasma composition experiment abroad ISEE 1 often show conical pitch angle distributions, that is, peak fluxes between 0 0 and 90 0 to the directions parallel or antiparallel to the magnetic field. Frequently, all three primary ionospheric ion species (H + , He + , and O + ) simultaneously exhibit conical distributions with peak fluxes at essentially the same pitch angle. A distinction is made here between unidirectional, or streaming, distributions, in which ions are traveling essentially from only one hemisphere, and symmetrical distributions, in which significant fluxes are observed traveling from both hemispheres. The orbital coverage for this survey was largely restricted to the night sector, approximately 2100--0600 LT, and moderate geomagnetic latitudes of 20 0 --40 0 . Also, lack of complete pitch angle coverage at all times may have reduced detection for conics with small cone angles. However, we may conclude that the unidirectional conical distributions observed in the northern hemisphere are always observed to be traveling from the northern hemisphere and that they exhibit the following characteristics relative to the symmetric distributions, in that they (1) are typically observed on higher L shells (that is, higher geomagnetic latitudes or larger geocentric distances or both), (2) tend to have significantly larger cone angles, and (3), are associated with higher magnetic activity levels

Isotopomer distributions in amino acids from a highly expressed protein as a proxy for those from total protein

Energy Technology Data Exchange (ETDEWEB)

Shaikh, Afshan; Shaikh, Afshan S.; Tang, Yinjie; Mukhopadhyay, Aindrila; Keasling, Jay D.

2008-06-27

{sup 13}C-based metabolic flux analysis provides valuable information about bacterial physiology. Though many biological processes rely on the synergistic functions of microbial communities, study of individual organisms in a mixed culture using existing flux analysis methods is difficult. Isotopomer-based flux analysis typically relies on hydrolyzed amino acids from a homogeneous biomass. Thus metabolic flux analysis of a given organism in a mixed culture requires its separation from the mixed culture. Swift and efficient cell separation is difficult and a major hurdle for isotopomer-based flux analysis of mixed cultures. Here we demonstrate the use of a single highly-expressed protein to analyze the isotopomer distribution of amino acids from one organism. Using the model organism E. coli expressing a plasmid-borne, his-tagged Green Fluorescent Protein (GFP), we show that induction of GFP does not affect E. coli growth kinetics or the isotopomer distribution in nine key metabolites. Further, the isotopomer labeling patterns of amino acids derived from purified GFP and total cell protein are indistinguishable, indicating that amino acids from a purified protein can be used to infer metabolic fluxes of targeted organisms in a mixed culture. This study provides the foundation to extend isotopomer-based flux analysis to study metabolism of individual strains in microbial communities.

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)

Visualization of neutron flux and power distributions in TRIGA Mark II reactor as an educational tool

International Nuclear Information System (INIS)

Snoj, Luka; Ravnik, Matjaz; Lengar, Igor

2008-01-01

Modern Monte Carlo computer codes (e.g. MCNP) for neutron transport allow calculation of detailed neutron flux and power distribution in complex geometries with resolution of ∼1 mm. Moreover they enable the calculation of individual particle tracks, scattering and absorption events. With the use of advanced software for 3D visualization (e.g. Amira, Voxler, etc.) one can create and present neutron flux and power distribution in a 'user friendly' way convenient for educational purposes. One can view axial, radial or any other spatial distribution of the neutron flux and power distribution in a nuclear reactor from various perspectives and in various modalities of presentation. By visualizing the distribution of scattering and absorption events and individual particle tracks one can visualize neutron transport parameters (mean free path, diffusion length, macroscopic cross section, up-scattering, thermalization, etc.) from elementary point of view. Most of the people remember better, if they visualize the processes. Therefore the representation of the reactor and neutron transport parameters is a convenient modern educational tool for the (nuclear power plant) operators, nuclear engineers, students and specialists involved in reactor operation and design. The visualization of neutron flux and power distributions in Jozef Stefan Institute TRIGA Mark II research reactor is treated in the paper. The distributions are calculated with MCNP computer code and presented using Amira and Voxler software. The results in the form of figures are presented in the paper together with comments qualitatively explaining the figures. (authors)

Noninvasive ultrasonic measurements of temperature distribution and heat fluxes in nuclear systems

International Nuclear Information System (INIS)

Jia, Yunlu; Skliar, Mikhail

2015-01-01

Measurements of temperature and heat fluxes through structural materials are important in many nuclear systems. One such example is dry storage casks (DSC) that are built to store highly radioactive materials, such as spent nuclear reactor fuel. The temperature inside casks must be maintained within allowable limits of the fuel assemblies and the DSC components because many degradation mechanisms are thermally controlled. In order to obtain direct, real-time measurements of temperature distribution without insertion of sensing elements into harsh environment of storage casks, we are developing noninvasive ultrasound (US) methods for measuring spatial distribution of temperature inside solid materials, such as concrete overpacks, steel casings, thimbles, and rods. The measured temperature distribution can then be used to obtain heat fluxes that provide calorimetric characterisation of the fuel decay, fuel distribution inside the cask, its integrity, and accounting of nuclear materials. The physical basis of the proposed approach is the temperature dependence of the speed of sound in solids. By measuring the time it takes an ultrasound signal to travel a known distance between a transducer and a receiver, the indication about the temperature distribution along the path of the ultrasound propagation may be obtained. However, when temperature along the path of US propagation is non-uniform, the overall time of flight of an ultrasound signal depends on the temperature distribution in a complex and unknown way. To overcome this difficulty, the central idea of our method is to create an US propagation path inside material of interest which incorporates partial ultrasound reflectors (back scatterers) at known locations and use the train of created multiple echoes to estimate the temperature distribution. In this paper, we discuss experimental validation of this approach, the achievable accuracy and spatial resolution of the measured temperature profile, and stress the

Spatial distribution of potential near surface moisture flux at Yucca Mountain

International Nuclear Information System (INIS)

Flint, A.L.; Flint, L.E.

1994-01-01

An estimate of the areal distribution of present-day surface liquid moisture flux at Yucca Mountain was made using field measured water contents and laboratory measured rock properties. Using available data for physical and hydrologic properties (porosity, saturated hydraulic conductivity, moisture retention functions) of the volcanic rocks, surface lithologic units that are hydrologically similar were delineated. Moisture retention and relative permeability functions were assigned to each surface unit based on the similarity of the mean porosity and saturated hydraulic conductivity of the surface unit to laboratory samples of the same lithology. The potential flux into the mountain was estimated for each surface hydrologic unit using the mean saturated hydraulic conductivity for each unit and assuming all matrix flow. Using measured moisture profiles for each of the surface units, estimates were made of the depth at which seasonal fluctuations diminish and steady state downward flux conditions are likely to exist. The hydrologic properties at that depth were used with the current relative saturation of the tuff, to estimate flux as the unsaturated hydraulic conductivity. This method assumes a unit gradient. The range in estimated flux was 0.02 mm/yr for the welded Tiva Canyon to 13.4 mm/yr for the nonwelded Paintbrush Tuff. The areally averaged flux was 1.4 mm/yr. The major zones of high flux occur to the north of the potential repository boundary where the nonwelded tuffs are exposed in the major drainages

Spatial distribution of potential near surface moisture flux at Yucca Mountain

International Nuclear Information System (INIS)

Flint, A.L.; Flint, L.E.

1994-01-01

An estimate of the areal distribution of present-day surface liquid moisture flux at Yucca Mountain was made using field measured water contents and laboratory measured rock properties. Using available data for physical and hydrologic properties (porosity, saturated hydraulic conductivity moisture retention functions) of the volcanic rocks, surface lithologic units that are hydrologically similar were delineated. Moisture retention and relative permeability functions were assigned to each surface unit based on the similarity of the mean porosity and saturated hydraulic conductivity of the surface unit to laboratory samples of the same lithology. The potential flux into the mountain was estimated for each surface hydrologic unit using the mean saturated hydraulic conductivity for each unit and assuming all matrix flow. Using measured moisture profiles for each of the surface units, estimates were made of the depth at which seasonal fluctuations diminish and steady state downward flux conditions are likely to exist. The hydrologic properties at that depth were used with the current relative saturation of the tuff, to estimate flux as the unsaturated hydraulic conductivity. This method assumes a unit gradient. The range in estimated flux was 0.02 mm/yr for the welded Tiva Canyon to 13.4 mm/yr for the nonwelded Paintbrush Tuff. The areally averaged flux was 1.4 mm/yr. The major zones of high flux occur to the north of the potential repository boundary where the nonwelded tuffs are exposed in the major drainages

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

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

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

Measurement of two-dimensional thermal neutron flux in a water phantom and evaluation of dose distribution characteristics

International Nuclear Information System (INIS)

Yamamoto, Kazuyoshi; Kumada, Hiroaki; Kishi, Toshiaki; Torii, Yoshiya; Horiguchi, Yoji

2001-03-01

To evaluate nitrogen dose, boron dose and gamma-ray dose occurred by neutron capture reaction of the hydrogen at the medical irradiation, two-dimensional distribution of the thermal neutron flux is very important because these doses are proportional to the thermal neutron distribution. This report describes the measurement of the two-dimensional thermal neutron distribution in a head water phantom by neutron beams of the JRR-4 and evaluation of the dose distribution characteristic. Thermal neutron flux in the phantom was measured by gold wire placed in the spokewise of every 30 degrees in order to avoid the interaction. Distribution of the thermal neutron flux was also calculated using two-dimensional Lagrange's interpolation program (radius, angle direction) developed this time. As a result of the analysis, it was confirmed to become distorted distribution which has annular peak at outside of the void, though improved dose profile of the deep direction was confirmed in the case which the radiation field in the phantom contains void. (author)

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

Science.gov (United States)

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

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.

Flux Analysis of the Trypanosoma brucei Glycolysis Based on a Multiobjective-Criteria Bioinformatic Approach

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Amine Ghozlane

2012-01-01

Full Text Available Trypanosoma brucei is a protozoan parasite of major of interest in discovering new genes for drug targets. This parasite alternates its life cycle between the mammal host(s (bloodstream form and the insect vector (procyclic form, with two divergent glucose metabolism amenable to in vitro culture. While the metabolic network of the bloodstream forms has been well characterized, the flux distribution between the different branches of the glucose metabolic network in the procyclic form has not been addressed so far. We present a computational analysis (called Metaboflux that exploits the metabolic topology of the procyclic form, and allows the incorporation of multipurpose experimental data to increase the biological relevance of the model. The alternatives resulting from the structural complexity of networks are formulated as an optimization problem solved by a metaheuristic where experimental data are modeled in a multiobjective function. Our results show that the current metabolic model is in agreement with experimental data and confirms the observed high metabolic flexibility of glucose metabolism. In addition, Metaboflux offers a rational explanation for the high flexibility in the ratio between final products from glucose metabolism, thsat is, flux redistribution through the malic enzyme steps.

Spatial distribution of neutron flux for the A-711 neutron generator

International Nuclear Information System (INIS)

Essiet, A. E.; Owolabi, S. A.; Adesanmi, C. A.; Balogun, F. A.

1996-01-01

The spatial distribution of neutron flux for the Kaman sciences A-711 neutron generator recently installed at the Centre for Energy Research and Development (CERD), Ile-Ife Nigeria has been determined. At an operational tube current of 2.0 mA and high voltage power supply (HVPS) of 158 kV, the neutron flux increases from 1.608 ± 0.021*10 8 n/cm 2 s at the top of the irradiated plastic vial to 2.640 ± 0.022*10 8 n/cm 2 s at the centre, and then decreases to 1.943 ± 0.02* 8 n/cm 2 s at the bottom. The flux density is strongly dependent on the diameter of deuteron at the tritium target, and within this range a source strength of 10 8 n/s has been measured for the A-711 neutron generator

SLAROM, Neutron Flux Distribution and Spectra in Lattice Cell

International Nuclear Information System (INIS)

Nakagawa, M.; Tsuchihashi, K.

2002-01-01

1 - Description of program or function: SLAROM solves the neutron integral transport equations to determine flux distribution and spectra in a lattice and calculates cell averaged effective cross sections. 2 - Method of solution: Collision probability method for cell calculation and 1D diffusion for core calculation. 3 - Restrictions on the complexity of the problem: Variable dimensions are used throughout the program so that computer core requirements depend on a variety of program parameters

Calculation of the magnetic flux density distribution in type-II superconductors with finite thickness and well-defined geometry

International Nuclear Information System (INIS)

Forkl, A.; Kronmueller, H.

1995-01-01

The distribution of the critical current density j c (r) in hard type-II superconductors depends strongly on their sample geometry. Rules are given for the construction of j c (r). Samples with homogeneous thickness are divided into cakelike regions with a unique current direction. The spatial magnetic flux density distribution and the magnetic polarization of such a cakelike unit cell with homogeneous current density are calculated analytically. The magnetic polarization and magnetic flux density distribution of a superconductor in the mixed state is then given by an adequate superposition of the unit cell solutions. The theoretical results show good agreement with magneto-optically determined magnetic flux density distributions of a quadratic thin superconducting YBa 2 Cu 3 O 7-x film. The current density distribution is discussed for several sample geometries

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

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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.

Study of the neutron flux distribution in acylindrical reactor

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A. Vidal-Ferràndiz

2017-08-01

Full Text Available In the Energy Engineering Degree of the Universitat Politècnica de València, the students attend to the Nuclear Technology course, in which the basic knowledge of this technology is presented. A main objective of this technology is to obtain neutron population distribution inside a reactor core, in order to maintain the fission reaction chain. As this activity cannot be experimentally developed, mathematical modelling is of great importance to achieve such objective.  One of the computer laboratories proposed consists in the neutron flux determination analytically and numerically in a cylindrical geometry. The analytical solution makes use of the Bessel functions and is a good example of their applications. Alternatively, a numerical solution based on finite differences is used to obtain an approximate solution of the neutron flux. In this work, different discretizations of the cylindrical geometry are implemented and their results are compared.

Deciphering flux adjustments of engineered E. coli cells during fermentation with changing growth conditions

Energy Technology Data Exchange (ETDEWEB)

He, Lian [Washington Univ., St. Louis, MO (United States); Xiu, Yu [Rensselaer Polytechnic Inst., Troy, NY (United States); Beijing Univ. of Chemical Technology (China); Jones, J. Andrew [Rensselaer Polytechnic Inst., Troy, NY (United States); Hamilton College, Clinton, NY (United States); Baidoo, Edward E. K. [Joint BioEnergy Inst. (JBEI), Emeryville, CA (United States); Keasling, Jay D. [Joint BioEnergy Inst. (JBEI), Emeryville, CA (United States); Univ. of California, Berkeley, CA (United States); Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Technical Univ. of Denmark, Lyngby (Denmark); Tang, Yinjie J. [Washington Univ., St. Louis, MO (United States); Koffas, Mattheos A. G. [Rensselaer Polytechnic Inst., Troy, NY (United States)

2016-12-23

Microbial fermentation conditions are dynamic, due to transcriptional induction, nutrient consumption, or changes to incubation conditions. In this paper, ¹³C-metabolic flux analysis was used to characterize two violacein-producing E. coli strains with vastly different productivities, and to profile their metabolic adjustments resulting from external perturbations during fermentation. The two strains were first grown at 37 °C in stage 1, and then the temperature was transitioned to 20 °C in stage 2 for the optimal expression of the violacein synthesis pathway. After induction, violacein production was minimal in stage 3, but accelerated in stage 4 (early production phase) and 5 (late production phase) in the high producing strain, reaching a final concentration of 1.5 mmol/L. On the contrary, ~0.02 mmol/L of violacein was obtained from the low producing strain. To have a snapshot of the temporal metabolic changes in each stage, we performed ¹³C-MFA via isotopomer analysis of fast-turnover free metabolites. The results indicate strikingly stable flux ratios in the central metabolism throughout the early growth stages. In the late stages, however, the high producer rewired its flux distribution significantly, which featured an upregulated pentose phosphate pathway and TCA cycle, reflux from acetate utilization, negligible anabolic fluxes, and elevated maintenance loss, to compensate for nutrient depletion and drainage of some building blocks due to violacein overproduction. The low producer with stronger promoters shifted its relative fluxes in stage 5 by enhancing the flux through the TCA cycle and acetate overflow, while exhibiting a reduced biomass growth and a minimal flux towards violacein synthesis. Finally, interestingly, the addition of the violacein precursor (tryptophan) in the medium inhibited high producer but enhanced low producer's productivity, leading to hypotheses of unknown pathway regulations (such as metabolite

Phase transitions and flux distributions of SU(2) lattice gauge theory

International Nuclear Information System (INIS)

Peng, Yingcai.

1993-01-01

The strong interactions between quarks are believed to be described by Quantum Chromodynamics (QCD), which is a non-abelian SU(3) gauge theory. It is known that QCD undergoes a deconfining phase transition at very high temperatures, that is, at low temperatures QCD is in confined phase, at sufficient high temperatures it is in an unconfined phase. Also, quark confinement is believed to be due to string formation. In this dissertation the authors studied SU(2) gauge theory using numerical methods of LGT, which will provide some insights about the properties of QCD because SU(2) is similar to SU(3). They measured the flux distributions of a q bar q pair at various temperatures in different volumes. They find that in the limit of infinite volumes the flux distribution is different in the two phases. In the confined phase strong evidence is found for the string formation, however, in the unconfined phase there is no string formation. On the other hand, in the limit of zero temperature and finite volumes they find a clear signal for string formation in the large volume region, however, the string tension measured in intermediate volumes is due to finite volume effects, there is no intrinsic string formation. The color flux energies (action) of the q bar q pair are described by Michael sum rules. The original Michael sum rules deal with a static q bar q pair at zero temperature in infinite volumes. To check these sum rules with flux data at finite temperatures, they present a complete derivation for the sum rules, thus generalizing them to account for finite temperature effects. They find that the flux data are consistent with the prediction of generalized sum rules. The study elucidates the rich structures of QCD, and provides evidence for quark confinement and string formation. This supports the belief that QCD is a correct theory for strong interactions, and quark confinement can be explained by QCD

Development of a position-sensitive fission counter and measurement of neutron flux distributions

International Nuclear Information System (INIS)

Yamagishi, Hideshi; Soyama, Kazuhiko; Kakuta, Tsunemi

2001-08-01

A position-sensitive fission counter (PSFC) that operates in high neutron flux and high gamma-ray background such as at the side of a power reactor vessel has been developed. Neutron detection using the PSFC with a solenoid electrode is based on a delay-line method. The PSFC that has the outer diameter of 25 mm and the sensitive length of 1000 mm was manufactured for investigation of the performances. The PSFC provided output current pulses that were sufficiently higher than the alpha noise, though the PSFC has a solenoid electrode and large electrode-capacitance. The S/N ratio of PSFC outputs proved to be higher than that of ordinary fission counters with 200 mm sensitive length. A performance test to measure neutron flux distributions by a neutron measuring system with the PSFC was carried out by the side of a graphite pile, W2.4 x H1.4 x L1.2 m, with neutron sources, Am-Be 370 GBq x 2. It was confirmed that the neutron flux distribution was well measured with the system. (author)

Characteristics of ion distribution functions in dipolarizing flux bundles: Event studies

Science.gov (United States)

Runov, A.; Angelopoulos, V.; Artemyev, A.; Birn, J.; Pritchett, P. L.; Zhou, X.-Z.

2017-06-01

Taking advantage of multipoint observations from a repeating configuration of the five Time History of Events and Macroscale Interactions during Substorms (THEMIS) probes separated by 1 to 2 Earth radii (RE) along X, Y, and Z in the geocentric solar magnetospheric system (GSM), we study ion distribution functions collected by the probes during three dipolarizing flux bundle (DFB) events observed at geocentric distances 9 energy and twice the thermal energy, although the distribution in the ambient plasma sheet was isotropic. The anisotropic ion distribution in DFBs injected toward the inner magnetosphere may provide the free energy for waves and instabilities, which are important elements of particle energization.

Subchannel measurements of the equilibrium quality and mass flux distribution in a rod bundle

International Nuclear Information System (INIS)

Lahey, R.T. Jr.

1986-01-01

An experiment was performed to measure the equilibrium subchannel void and mass flux distribution in a simulated BWR rod bundle. These new equilibrium subchannel data are unique and represent an excellent basis for subchannel ''void drift'' model development and assessment. Equilibrium subchannel void and mass flux distributions have been determined from the data presented herein. While the form of these correlations agree with the results of previous theoretical investigations, they should be generalized with caution since the current data base has been taken at only one (low) system pressure. Clearly there is a need for equilibrium subchannel data at higher system pressures if mechanistic subchannel models are to be developed

Flux-probability distributions from the master equation for radiation transport in stochastic media

International Nuclear Information System (INIS)

Franke, Brian C.; Prinja, Anil K.

2011-01-01

We present numerical investigations into the accuracy of approximations in the master equation for radiation transport in discrete binary random media. Our solutions of the master equation yield probability distributions of particle flux at each element of phase space. We employ the Levermore-Pomraning interface closure and evaluate the effectiveness of closures for the joint conditional flux distribution for estimating scattering integrals. We propose a parameterized model for this joint-pdf closure, varying between correlation neglect and a full-correlation model. The closure is evaluated for a variety of parameter settings. Comparisons are made with benchmark results obtained through suites of fixed-geometry realizations of random media in rod problems. All calculations are performed using Monte Carlo techniques. Accuracy of the approximations in the master equation is assessed by examining the probability distributions for reflection and transmission and by evaluating the moments of the pdfs. The results suggest the correlation-neglect setting in our model performs best and shows improved agreement in the atomic-mix limit. (author)

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.

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

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

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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.

Foetal distribution and metabolism of N-Nitrosodiethylamine in mice

International Nuclear Information System (INIS)

Brittebo, E.B.; Lindgren, A.; Tjaelve, A.

1981-01-01

In pregnant NMRI mice, low-temperature autoradiography was used to study the distribution of N- 14 C-nitrosodiethylamine in foetal tissues, and autoradiography with heated tape-sections was used to trace nonvolatile metabolites. Autoradiography with 14 C-acetate was used to distinquish the part of the radiography which upon the degradation of N- 14 C-nitrosodiethylamine may be incorporated in the normal metabolism of the tissues. The results indicated that the non-metabolized N-nitrosodiethylamine passed to the foetuses with an even distribution in most foetal tissues on all the studied days of gestation (day 12, 14, 16 and 18). The autoradiographic results further indicated a metabolism of the substance in the mucosa of the foetal bronchial tree and in the foetal liver on day 18 of gestation, but not in earlier stages of pregnancy. This was substantiated by studies in vitro, which showed a marked capacity of the 18 day old foetal lung and liver (in contrast to tissues from 16 day old foetuses) to form 14 CO 2 from the N- 14 C-nitrosodiethylamine. Since the lung and liver are target tissues for the transplacental carcinogenesis of N-nitrosodiethylamine in NMRI mice, a causal relationship between metabolic ability and carcinogenesis may exist in these tissues. (Author)

Neutron flux distribution measurement in the elementary cell of the RB reactor

Energy Technology Data Exchange (ETDEWEB)

Takac, S [Boris Kidric Institute of Nuclear Sciences Vinca, Beograd (Yugoslavia)

1963-04-15

The distribution of thermal neutrons was measured in the elementary cell with dysprosium foils for different lattice pitches and the results obtained were given. From the distributions measured average fluxes were determined for every single zone. By using the published data concerning effective absorption cross sections thermal utilization factors were calculated and their changes given as functions of lattice pitches: l = 8.0 cm; 11.3 cm and 17.9 cm. (author)

Estimating the size of the solution space of metabolic networks

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Mulet Roberto

2008-05-01

Full Text Available Abstract Background Cellular metabolism is one of the most investigated system of biological interactions. While the topological nature of individual reactions and pathways in the network is quite well understood there is still a lack of comprehension regarding the global functional behavior of the system. In the last few years flux-balance analysis (FBA has been the most successful and widely used technique for studying metabolism at system level. This method strongly relies on the hypothesis that the organism maximizes an objective function. However only under very specific biological conditions (e.g. maximization of biomass for E. coli in reach nutrient medium the cell seems to obey such optimization law. A more refined analysis not assuming extremization remains an elusive task for large metabolic systems due to algorithmic limitations. Results In this work we propose a novel algorithmic strategy that provides an efficient characterization of the whole set of stable fluxes compatible with the metabolic constraints. Using a technique derived from the fields of statistical physics and information theory we designed a message-passing algorithm to estimate the size of the affine space containing all possible steady-state flux distributions of metabolic networks. The algorithm, based on the well known Bethe approximation, can be used to approximately compute the volume of a non full-dimensional convex polytope in high dimensions. We first compare the accuracy of the predictions with an exact algorithm on small random metabolic networks. We also verify that the predictions of the algorithm match closely those of Monte Carlo based methods in the case of the Red Blood Cell metabolic network. Then we test the effect of gene knock-outs on the size of the solution space in the case of E. coli central metabolism. Finally we analyze the statistical properties of the average fluxes of the reactions in the E. coli metabolic network. Conclusion We propose a

Magneto-optical imaging of magnetic flux distribution in high-Tc superconductors

International Nuclear Information System (INIS)

Ueno, K.; Murakamia, H.; Kawayama, I.; Doda, Y.; Tonouchi, M.; Chikumoto, N.

2004-01-01

Prototype systems of home-made magneto-optical microscopes were fabricated, and preliminary studies were carried out using Bi 2 Sr 2 CaCu 2 O 8+δ single crystals and an YBa 2 Cu 3 O 7-δ superconductor vortex flow transistor. In the study using BSCCO crystals, we succeeded in the observation of magnetic flux penetration into half-peeled thin flake region on the crystal surface, and it was found that the magnetic fluxes penetrate in characteristic one-dimensional alignment almost along the crystal a-axis. On the other hand, in the study using the YBCO device clear changes in the generated magnetic field distribution could be detected corresponding to the current direction

2-D temperature distribution and heat flux of PFC in 2011 KSTAR campaign

Energy Technology Data Exchange (ETDEWEB)

Bang, Eunnam, E-mail: bang14@nfri.re.kr; Hong, Suk-Ho; Yu, Yaowei; Kim, Kyungmin; Kim, Hongtack; Kim, Hakkun; Lee, Kunsu; Yang, Hyunglyul

2013-10-15

Highlights: • The heat flux on PFC tiles of 12 s pulse duration and 630 kA plasma current is about 0.02 MW/m{sup 2}. • When the cryopump is operated, the heat flux of CD is higher than without cryopump. • The more H-mode duration is long, the more heat flux on divertor is high. -- Abstract: KSTAR has reached a plasma current up to 630 kA, plasma duration up to 12 s, and has achieved high confinement mode (H-mode) in 2011 campaign. The heat flux of PFC tile was estimated from the temperature increase of PFC since 2010. The heat flux of PFC tiles increases significantly with higher plasma current and longer pulse duration. The time-averaged heat flux of shots in 2010 campaign (with 3 s pulse durations and I{sub p} of 611 kA) is 0.01 MW/m{sup 2} while that in 2011 campaign (with 12 s pulse duration and I{sub p} of 630 kA) is about 0.02 MW/m{sup 2}. The heat flux at divertor is 1.4–2 times higher than that at inboard limiter or passive stabilizer. With the cryopump operation, the heat flux at the central divertor is higher than that without cryopump. The heat flux at divertor is proportional to, of course, the duration of H-mode. Furthermore, a software tool, which visualizes the 2D temperature distribution of PFC tile and estimates the heat flux in real time, is developed.

Fermentation characteristics in conversion of organic acids obtained by oxidation of low-rank coals to poly({beta}-hydroxybutyrate) using A. eutrophus cells with some analysis on metabolic flux distribution; Kattan no ekisosanka de erareru yukisan wo suiso saikin wo riyoshite pori {beta}-hidorokishi rakusan (PHB) ni henkansaseru tameno baiyo kogakuteki kento to taisha ryusoku bunpu shisutemu kaiseki

Energy Technology Data Exchange (ETDEWEB)

Tsujimoto, Shoko.; Shin, Huidong.; Shimizu, Kazuyuki. [Kyushu Institute of Technology, Fukuoka (Japan). Department of Biochemical engineering and science; Mae, Kazuhiro.; Miura, Koichi. [Kyoto University, Kyoto (Japan). Department of Chemical Engineering

1999-03-10

Fermentation characteristics are investigated for the conversion of glycolate, acetate, formate, and malonate obtained by the oxidation of low-rank coals to poly ({beta}-hydrox butyrate) (PHB) using A. eutrophus cells. Based on the cultivation experiments using one of the organic acids as a sole carbon source, it is found that acetate is the most effectively converted to PHB. When mixed organic acids are used, formate is preferentially consumed, followed by acetate, and finally glycolate. Although malate can not be utilized, it is implied that it might change the pathway flux distributions based on the metabolic flux analysis. Namely, it shows competitive inhibition to succinate dehydrogenase so that its addition during fermentation results in flux reduction from succinate to maleic acid as well as glyoxylate flux and gluconeogenesis flux. It is also found that NADPH generated from isocitrate is preferentially utilized for the reaction from {alpha}-ketoglutarate to glutamate when NH{sub 3} concentration is high, while it is eventually used for the PHB production from acetoacetyl CoA as NH{sub 3} concentration decreases. (author)

MCNP and visualization of neutron flux and power distributions

International Nuclear Information System (INIS)

Snoj, L.; Lengar, I.; Zerovnik, G.; Ravnik, M.

2009-01-01

The visualization of neutron flux and power distributions in two nuclear reactors (TRIG A type research reactor and typical PWR) and one thermonuclear reactor (tokamak type) are treated in the paper. The distributions are calculated with MCNP computer code and presented using Amira and Voxler software. The results in the form of figures are presented in the paper together with comments qualitatively explaining the figures. The remembrance of most of the people is better, if they visualize a process. Therefore a representation of the reactor and neutron transport parameters is a convenient modern educational tool for (nuclear power plant) operators, nuclear engineers, students and specialists involved in reactor operation and design. Visualization is applicable not only in education and training, but also as a tool for core and irradiation planning. (authors)

Fast Radio Bursts’ Recipes for the Distributions of Dispersion Measures, Flux Densities, and Fluences

Science.gov (United States)

Niino, Yuu

2018-05-01

We investigate how the statistical properties of dispersion measure (DM) and apparent flux density/fluence of (nonrepeating) fast radio bursts (FRBs) are determined by unknown cosmic rate density history [ρ FRB(z)] and luminosity function (LF) of the transient events. We predict the distributions of DMs, flux densities, and fluences of FRBs taking account of the variation of the receiver efficiency within its beam, using analytical models of ρ FRB(z) and LF. Comparing the predictions with the observations, we show that the cumulative distribution of apparent fluences suggests that FRBs originate at cosmological distances and ρ FRB increases with redshift resembling the cosmic star formation history (CSFH). We also show that an LF model with a bright-end cutoff at log10 L ν (erg s‑1 Hz‑1) ∼ 34 are favored to reproduce the observed DM distribution if ρ FRB(z) ∝ CSFH, although the statistical significance of the constraints obtained with the current size of the observed sample is not high. Finally, we find that the correlation between DM and flux density of FRBs is potentially a powerful tool to distinguish whether FRBs are at cosmological distances or in the local universe more robustly with future observations.

Measurement of neutron flux distribution by semiconductor detector

International Nuclear Information System (INIS)

Obradovic, D.; Bosevski, T.

1964-01-01

Application of semiconductor detectors for measuring neutron flux distribution is about 10 times faster than measurements by activation foils and demands significantly lower reactor power. Following corrections are avoided: mass of activation foils which influences the self shielding, nuclear decay during activity measurements; counter dead-time. It is possible to control the measured data during experiment and repeat measurements if needed. Precision of the measurement is higher since it is possible to choose the wanted statistics. The method described in this paper is applied for measurements at the RB reactor. It is concluded that the method is suitable for fast measurements but the activation analysis is still indispensable

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...

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.

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.

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.

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

Thermal neutron flux distribution in the ET R R-1 reactor core as experimentally measured and theoretically calculated by the code triton

Energy Technology Data Exchange (ETDEWEB)

Imam, M [National center for nuclear safety and radiation control, atomic energy authority, Cairo, (Egypt)

1995-10-01

Thermal neutron flux distributions that were measured earlier at the ET-R R-1 reactor are compared with those calculated by the three dimensional diffusion code Triton. This comparison was made for the horizontal and vertical flux distributions. The horizontal thermal flux distributions considered in this comparison were along the core diagonals at two planes of different heights from core bottom, where one at a level passing through the control rod at core center and the other at a level below this control rod. In the meantime all the control rods were taken into consideration. The effect of the existence of a water cavity inside the core as well as the influence of the control rods on the thermal flux are illustrated in this work. The vertical thermal flux distributions considered in the comparison were at two positions in core namely; one along the core height the horizontal reactor power distribution along the core height and the horizontal reactor power distribution along the core diagonal as calculated by the code Triton are also given this work. 8 figs., 1 tab.

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

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....

Measurement of the neutron flux distributions, epithermal index, Westcott thermal neutron flux in the irradiation capsules of hydraulic conveyer (Hyd) and pneumatic tubes (Pn) facilities of the KUR

International Nuclear Information System (INIS)

Chatani, Hiroshi

2001-05-01

The reactions of Au(n, γ) 198 Au and Ti(n, p) 47 or 48 Sc were used for the measurements of the thermal and epithermal (thermal + epithermal) and the fast neutron flux distributions, respectively. In the case of Hyd (Hydraulic conveyer), the thermal + epithermal and fast neutron flux distributions in the horizontal direction in the capsule are especially flat; the distortion of the fluxes are 0.6% and 5.4%, respectively. However, these neutron fluxes in the vertical direction are low at the top and high at the bottom of the capsule. These differences between the top and bottom are 14% for both distributions. On the other hand, in polyethylene capsules of Pn-1, 2, 3 (Pneumatic tubes Nos. 1, 2, 3), in contrast with Hyd, these neutron flux distributions in the horizontal direction have gradients of 8 - 18% per 2.5 cm diameter, and those on the vertical axis have a distortion of approximately 5%. The strength of the epithermal dE/E component relative to the neutron density including both thermal and epithermal neutrons, i.e., the epithermal index, for the hydraulic conveyer (Hyd) and pneumatic tube No.2 (Pn-2), in which the irradiation experiments can be achieved, are determined by the multiple foil activation method using the reactions of Au(n, γ) 198 Au and Co(n, γ) 60(m+g) Co. The epithermal index observed in an aluminum capsule of Hyd is 0.034-0.04, and the Westcott thermal neutron flux is 1.2x10 14 cm -2 sec -1 at approximately 1 cm above the bottom. The epithermal index in a Pn-2 polyethylene capsule was measured by not only the multiple foil activation method but also the Cd-ratio method in which the Au(n, γ) 198 Au reaction in a cadmium cover is also used. The epithermal index is 0.045 - 0.055, and the thermal neutron flux is 1.8x10 13 cm -2 sec -1 . (J.P.N.)

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.

Numerical Analysis on Heat Flux Distribution through the Steel Liner of the Ex-vessel Core Catcher

Energy Technology Data Exchange (ETDEWEB)

Oh, Se Hong; Choi, Choeng Ryul [ELSOLTEC, Yongin (Korea, Republic of); Kim, Byung Jo; Lee, Kyu Bok [KEPCO, Gimcheon (Korea, Republic of); Hwang, Do Hyun [KHNP-CRI, Daejeon (Korea, Republic of)

2016-05-15

In order to prevent material failure of steel container of the core catcher system due to high temperatures, heat flux through the steel liner wall must be kept below the critical heat flux (CHF), and vapor dry-out of the cooling channel must be avoided. In this study, CFD methodology has been developed to simulate the heat flux distribution in the core catcher system, involving following physical phenomena: natural convection in the corium pool, boiling heat transfer and solidification/melting of the corium. A CFD methodology has been developed to simulate the thermal/hydraulic phenomena in the core catcher system, and a numerical analysis has been carried out to estimate the heat flux through the steel liner of the core catcher. High heat flux values are formed at the free surface of the corium pool. However, the heat flux through the steel liner is maintained below the critical heat flux.

Temporal fluxomics reveals oscillations in TCA cycle flux throughout the mammalian cell cycle.

Science.gov (United States)

Ahn, Eunyong; Kumar, Praveen; Mukha, Dzmitry; Tzur, Amit; Shlomi, Tomer

2017-11-06

Cellular metabolic demands change throughout the cell cycle. Nevertheless, a characterization of how metabolic fluxes adapt to the changing demands throughout the cell cycle is lacking. Here, we developed a temporal-fluxomics approach to derive a comprehensive and quantitative view of alterations in metabolic fluxes throughout the mammalian cell cycle. This is achieved by combining pulse-chase LC-MS-based isotope tracing in synchronized cell populations with computational deconvolution and metabolic flux modeling. We find that TCA cycle fluxes are rewired as cells progress through the cell cycle with complementary oscillations of glucose versus glutamine-derived fluxes: Oxidation of glucose-derived flux peaks in late G1 phase, while oxidative and reductive glutamine metabolism dominates S phase. These complementary flux oscillations maintain a constant production rate of reducing equivalents and oxidative phosphorylation flux throughout the cell cycle. The shift from glucose to glutamine oxidation in S phase plays an important role in cell cycle progression and cell proliferation. © 2017 The Authors. Published under the terms of the CC BY 4.0 license.

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

The effect of temperature and the control rod position on the spatial neutron flux distribution in the Syrian Miniature Neutron Source Reactor

International Nuclear Information System (INIS)

Khattab, K.; Omar, H.; Ghazi, N.

2007-01-01

The effect of water and fuel temperature increase and changes in the control rod positions on the spatial neutron flux distribution in the Syrian Miniature Neutron Source Reactor (MNSR) is discussed. The cross sections of all the reactor components at different temperatures are generated using the WIMSD4 code. These group constants are used then in the CITATION code to calculate the special neutron flux distribution using four energy groups. This work shows that water and fuel temperature increase in the reactor during the reactor daily operating time does not affect the spatial neutron flux distribution in the reactor. Changing the control rod position does not affect as well the spatial neutron flux distribution except in the region around the control rod position. This stability in the spatial neutron flux distribution, especially in the inner and outer irradiation sites, makes MNSR as a good tool for the neutron activation analysis (NAA) technique and production of radioisotopes with medium or short half lives during the reactor daily operating time. (author)

The use of thallium diethyldithiocarbamate for mapping CNS potassium metabolism and neuronal activity: Tl+ -redistribution, Tl+ -kinetics and Tl+ -equilibrium distribution.

Science.gov (United States)

Wanger, Tim; Scheich, Henning; Ohl, Frank W; Goldschmidt, Jürgen

2012-07-01

The potassium (K(+)) analogue thallium (Tl(+)) can be used as a tracer for mapping neuronal activity. However, because of the poor blood-brain barrier (BBB) K(+) -permeability, only minute amounts of Tl(+) enter the brain after systemic injection of Tl(+) -salts like thallium acetate (TlAc). We have recently shown that it is possible to overcome this limitation by injecting animals with the lipophilic chelate complex thallium diethyldithiocarbamate (TlDDC), that crosses the BBB and releases Tl(+) prior to neuronal or glial uptake. TlDDC can thus be used for mapping CNS K(+) metabolism and neuronal activity. Here, we analyze Tl(+) -kinetics in the rodent brain both experimentally and using simple mathematical models. We systemically injected animals either with TlAc or with TlDDC. Using an autometallographic method we mapped the brain Tl(+) -distribution at various time points after injection. We show that the patterns and kinetics of Tl(+) -redistribution in the brain are essentially the same irrespective of whether animals have been injected with TlAc or TlDDC. Data from modeling and experiments indicate that transmembrane Tl(+) -fluxes in cells within the CNS in vivo equilibrate at similar rates as K(+) -fluxes in vitro. This equilibration is much faster than and largely independent of the equilibration of Tl(+) -fluxes across the BBB. The study provides further proof-of-concept for the use of TlDDC for mapping neuronal activity and CNS K(+) -metabolism. A theoretical guideline is given for the use of K(+) -analogues for imaging neuronal activity with general implications for the use of metal ions in neuroimaging. © 2012 The Authors. Journal of Neurochemistry © 2012 International Society for Neurochemistry.

Equilibrium quality and mass flux distributions in an adiabatic three-subchannel test section

International Nuclear Information System (INIS)

Yadigaroglu, G.; Maganas, A.

1993-01-01

An experiment was designed to measure the fully-developed quality and mass flux distributions in an adiabatic three-subchannel test section. The three subchannels had the geometrical characteristics of the corner, side, and interior subchannels of a BWR-5 rod bundle. Data collected with Refrigerant-144 at pressures ranging from 7 to 14 bar, simulating operation with water in the range 55 to 103 bar are reported. The average mass flux and quality in the test section were in the ranges 1300 to 1750 kg/m s and -0.03 to 0.25, respectively. The data are analyzed and presented in various forms

Measured and Predicted Neutron Flux Distributions in a Material Surrounding a Cylindrical Duct

Energy Technology Data Exchange (ETDEWEB)

Nilsson, J; Sandlin, R

1966-03-15

The radial fast neutron flux attenuations in the material (iron) surrounding ducts of diameters 7, 9, and 15 cm and total duct length of about 1.5 m have been investigated with and without neutron scattering cans filled with D{sub 2}O in the duct. Experimentally the problem was solved by the use of foil activation techniques. Theoretically it was attacked by, in the first place, a Monte Carlo program specially written for this purpose and utilizing an importance sampling technique. In the second place non- and single-scattering removal flux codes were tried, and also simple hand calculations. The Monte Carlo results accounted well for the fast flux attenuation, while the non- and single-scattering methods overestimated the attenuation generally by a factor of 10 or less. Simple hand calculations using three empirical parameters could be fitted to the measured data within a factor of 1.2 - 1.3 at penetration depths greater than 3 - 4 cm. The distribution of the D{sub 2}O-scattered flux could well be described in terms of single scattering.

Sequential metabolic phases as a means to optimize cellular output in a constant environment.

Science.gov (United States)

Palinkas, Aljoscha; Bulik, Sascha; Bockmayr, Alexander; Holzhütter, Hermann-Georg

2015-01-01

Temporal changes of gene expression are a well-known regulatory feature of all cells, which is commonly perceived as a strategy to adapt the proteome to varying external conditions. However, temporal (rhythmic and non-rhythmic) changes of gene expression are also observed under virtually constant external conditions. Here we hypothesize that such changes are a means to render the synthesis of the metabolic output more efficient than under conditions of constant gene activities. In order to substantiate this hypothesis, we used a flux-balance model of the cellular metabolism. The total time span spent on the production of a given set of target metabolites was split into a series of shorter time intervals (metabolic phases) during which only selected groups of metabolic genes are active. The related flux distributions were calculated under the constraint that genes can be either active or inactive whereby the amount of protein related to an active gene is only controlled by the number of active genes: the lower the number of active genes the more protein can be allocated to the enzymes carrying non-zero fluxes. This concept of a predominantly protein-limited efficiency of gene expression clearly differs from other concepts resting on the assumption of an optimal gene regulation capable of allocating to all enzymes and transporters just that fraction of protein necessary to prevent rate limitation. Applying this concept to a simplified metabolic network of the central carbon metabolism with glucose or lactate as alternative substrates, we demonstrate that switching between optimally chosen stationary flux modes comprising different sets of active genes allows producing a demanded amount of target metabolites in a significantly shorter time than by a single optimal flux mode at fixed gene activities. Our model-based findings suggest that temporal expression of metabolic genes can be advantageous even under conditions of constant external substrate supply.

Measurements of neutron flux distributions in the core of the Ljubljana TRIGA Mark II Reactor

International Nuclear Information System (INIS)

Rant, J.; Ravnik, M.; Mele, I.; Dimic, V.

2008-01-01

Recently the Ljubljana TRIGA Mark II Reactor has been refurbished and upgraded to pulsed operation. To verify the core design calculations using TRIGAP and PULSTR1 codes and to obtain necessary data for future irradiation and neutron beam experiments, an extensive experimental program of neutron flux mapping and neutron field characterization was carried out. Using the existing neutron measuring thimbles complete axial and radial distributions in two radial directions were determined for two different core configurations. For one core configuration the measurements were also carried out in the pulsed mode. For flux distributions thin Cu (relative measurements) and diluted Au wires (absolute values) were used. For each radial position the cadmium ratio was determined in two axial levels. The core configuration was rather uniform, well defined (fresh fuel of a single type, including fuelled followers) and compact (no irradiation channels or gaps), offering unique opportunity to test the computer codes for TRIGA reactor calculations. The neutron flux measuring procedures and techniques are described and the experimental results are presented. The agreement between the predicted and measured power peaking factors are within the error limits of the measurements (<±5%) and calculations (±10%). Power peaking occurs in the B ring, and in the A ring (centre) there is a significant flux depression. (authors)

Magnetic Flux Distribution of Linear Machines with Novel Three-Dimensional Hybrid Magnet Arrays

Directory of Open Access Journals (Sweden)

Nan Yao

2017-11-01

Full Text Available The objective of this paper is to propose a novel tubular linear machine with hybrid permanent magnet arrays and multiple movers, which could be employed for either actuation or sensing technology. The hybrid magnet array produces flux distribution on both sides of windings, and thus helps to increase the signal strength in the windings. The multiple movers are important for airspace technology, because they can improve the system’s redundancy and reliability. The proposed design concept is presented, and the governing equations are obtained based on source free property and Maxwell equations. The magnetic field distribution in the linear machine is thus analytically formulated by using Bessel functions and harmonic expansion of magnetization vector. Numerical simulation is then conducted to validate the analytical solutions of the magnetic flux field. It is proved that the analytical model agrees with the numerical results well. Therefore, it can be utilized for the formulation of signal or force output subsequently, depending on its particular implementation.

Reconstructing 3D profiles of flux distribution in array of unshunted Josephson junctions from 2D scanning SQUID microscope images

International Nuclear Information System (INIS)

Nascimento, F.M.; Sergeenkov, S.; Araujo-Moreira, F.M.

2012-01-01

By using a specially designed algorithm (based on utilizing the so-called Hierarchical Data Format), we report on successful reconstruction of 3D profiles of local flux distribution within artificially prepared arrays of unshunted Nb-AlO x -Nb Josephson junctions from 2D surface images obtained via the scanning SQUID microscope. The analysis of the obtained results suggest that for large sweep areas, the local flux distribution significantly deviates from the conventional picture and exhibits a more complicated avalanche-type behavior with a prominent dendritic structure. -- Highlights: ► The penetration of external magnetic field into an array of Nb-AlO x -Nb Josephson junctions is studied. ► Using Scanning SQUID Microscope, 2D images of local flux distribution within array are obtained. ► Using specially designed pattern recognition algorithm, 3D flux profiles are reconstructed from 2D images.

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.

High-resolution dichroic imaging of magnetic flux distributions in superconductors with scanning x-ray microscopy

Energy Technology Data Exchange (ETDEWEB)

Ruoss, Stephen; Stahl, Claudia; Weigand, Markus; Schuetz, Gisela [Max-Planck-Institut fuer Intelligente Systeme, Stuttgart (Germany); Albrecht, Joachim [Research Institute for Innovative Surfaces, FINO, Aalen University (Germany)

2015-07-01

The penetration of magnetic flux into the high-temperature superconductor YBCO has been observed using a new high-resolution technique based on X-ray magnetic circular dichroism (XMCD). Superconductors coated with thin soft magnetic layers of CoFeB are observed in a scanning x-ray microscope providing cooling of the sample down to 83 K under the influence of external magnetic fields. Resulting electrical currents create an inhomogeneous magnetic field distribution above the superconductor which leads to a local reorientation of the ferromagnetic layer. X-ray absorption measurements with circular polarized radiation allows the analysis of the magnetic flux distribution in the superconductor via the ferromagnetic layer. In this work we present first images taken at 83K with high spatial resolution in the nanoscale.

Airborne methane remote measurements reveal heavy-tail flux distribution in Four Corners region.

Science.gov (United States)

Frankenberg, C.

2016-12-01

Methane (CH4) impacts climate as the second strongest anthropogenic greenhouse gas and air quality by influencing tropospheric ozone levels. Space-based observations have identified the Four Corners region in the Southwest United States as an area of large CH4 enhancements. We conducted an airborne campaign in Four Corners during April 2015 with the next-generation Airborne Visible/Infrared Imaging Spectrometer (near-infrared) and Hyperspectral Thermal Emission Spectrometer (thermal infrared) imaging spectrometers to better understand the source of methane by measuring methane plumes at 1- to 3-m spatial resolution. Our analysis detected more than 250 individual methane plumes from fossil fuel harvesting, processing, and distributing infrastructures, spanning an emission range from the detection limit ˜ 2 kg/h to 5 kg/h through ˜ 5,000 kg/h. Observed sources include gas processing facilities, storage tanks, pipeline leaks, natural seeps and well pads, as well as a coal mine venting shaft. Overall, plume enhancements and inferred fluxes follow a lognormal distribution, with the top 10% emitters contributing 49 to 66% to the inferred total point source flux of 0.23 Tg/y to 0.39 Tg/y. We will summarize the campaign results and provide an overview of how airborne remote sensing can be used to detect and infer methane fluxes over widespread geographic areas and how new instrumentation could be used to perform similar observations from space.

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

Effect of thermohydraulic parameter on the flux distribution and the effective multiplication factor

International Nuclear Information System (INIS)

Mello, J.C.; Valladares, G.L.

1990-01-01

The influence of two thermohydraulics parameters; the coolant flow velocity along the reactor channels and the increase of the average water temperature through the core, on the thermal flux distribution and on the effective multiplication factor, was studied in a radioisotopes production reactor. The results show that, for a fixed values of the thermohydraulics parameters reffered above, there are limits for the reactor core volume reduction for each value of the V sub(mod)/V sub(comb) ratio. These thermohydraulics conditions determine the higher termal flux value in the flux-trap and the lower value of the reactor effective multiplication factor. It is also show that there is a V sub(mod)/V sub(comb) ratio value that correspond to the higher value of the lower effective multiplication factor. These results was interpreted and comment using fundamentals concepts and relations of reactor physics. (author)

Two dimensional electron transport in disordered and ordered distributions of magnetic flux vortices

International Nuclear Information System (INIS)

Nielsen, M.; Hedegaard, P.

1994-04-01

We have considered the conductivity properties of a two dimensional electron gas (2DEG) in two different kinds of inhomogeneous magnetic fields, i.e. a disordered distribution of magnetic flux vortices, and a periodic array of magnetic flux vortices. The work falls in two parts. In the first part we show how the phase shifts for an electron scattering on an isolated vortex, can be calculated analytically, and related to the transport properties through the differential cross section. In the second part we present numerical results for the Hall conductivity of the 2DEG in a periodic array of flux vortices found by exact diagonalization. We find characteristic spikes in the Hall conductance, when it is plotted against the filling fraction. It is argued that the spikes can be interpreted in terms of ''topological charge'' piling up across local and global gaps in the energy spectrum. (au) (23 refs.)

Equilibrium quality and mass flux distributions in an adiabatic three-subchannel test section

International Nuclear Information System (INIS)

Yadigaroglu, G.; Maganas, A.

1995-01-01

An experiment was designed to measure the fully developed quality and mass flux distributions in an adiabatic three-subchannel test section. The three subchannels had the geometrical characteristics of the corner, side, and interior subchannels of a boiling water reactor (BWR-5) rod bundle. Data collected with Refrigerant-114 at pressures ranging from 7 to 14 bars, simulating operation with water in the range 55 to 103 bars are reported. The average mass flux and quality in the test section were in the ranges 1,300 to 1,750 kg/m 2 · s and -0.03 to 0.25, respectively. The data are analyzed and presented in various forms

Fast neutron flux and intracranial dose distribution at a neutron irradiation facility

International Nuclear Information System (INIS)

Matsumoto, Tetsuo; Aizawa, Otohiko; Nozaki, Tetsuya

1981-01-01

A head phantom filled with water was used to measure the fast neutron flux using 115 In(n, n')sup(115m)In and 103 Rh(n, n')sup(103m)Rh reactions. γ-ray from sup(115m)In and x-ray from sup(103m)Rh were detected by a Ge(Li) and a Na(Tl)I counter, respectively. TLD was used to investigate the γ-dose rate distribution inside the phantom. Flux of fast neutron inside the phantom was about 1 x 10 6 n/cm 2 sec, which was 3 order smaller than that of thermal neutron. The fast neutron flux decreased to 1/10 at 15 cm depth, and γ-dose rate was about 200 R/h at 100 kW inside the phantom. Total dose at the surface was 350 rad/h, to which, fast neutrons contributed more than γ-rays. The rate of fast neutron dose was about 10% of thermal neutron's in Kerma dose unit (rad), however, the rate was highly dependent on RBE value. (Nakanishi, T.)

Measurement and analysis of neutron flux distribution of STACY heterogeneous core by position sensitive proportional counter. Contract research

CERN Document Server

Murazaki, M; Uno, Y

2003-01-01

We have measured neutron flux distribution around the core tank of STACY heterogeneous core by position sensitive proportional counter (PSPC) to develop the method to measure reactivity for subcritical systems. The neutron flux distribution data in the position accuracy of +-13 mm have been obtained in the range of uranium concentration of 50g/L to 210g/L both in critical and in subcritical state. The prompt neutron decay constant, alpha, was evaluated from the measurement data of pulsed neutron source experiments. We also calculated distribution of neutron flux and sup 3 He reaction rates at the location of PSPC by using continuous energy Monte Carlo code MCNP. The measurement data was compared with the calculation results. As results of comparison, calculated values agreed generally with measurement data of PSPC with Cd cover in the region above half of solution height, but the difference between calculated value and measurement data was large in the region below half of solution height. On the other hand, ...

Absorption, tissue distribution, excretion, and metabolism of clothianidin in rats.

Science.gov (United States)

Yokota, Tokunori; Mikata, Kazuki; Nagasaki, Hiromi; Ohta, Kazunari

2003-11-19

Absorption, distribution, excretion, and metabolism of clothianidin [(E)-1-(2-chloro-1,3-thiazol-5-ylmethyl)-3-methyl-2-nitroguanidine] were investigated after a single oral administration of [nitroimino-(14)C]- or [thiazolyl-2-(14)C]clothianidin to male and female rats at a dose of 5 mg/kg of body weight (bw) (low dose) or 250 mg/kg of bw (high dose). The maximum concentration of carbon-14 in blood occurred 2 h after administration of the low oral dose for both labeled clothianidins, and then the concentration of carbon-14 in blood decreased with a half-life of 2.9-4.0 h. The orally administered carbon-14 was rapidly and extensively distributed to all tissues and organs within 2 h after administration, especially to the kidney and liver, but was rapidly and almost completely eliminated from all tissues and organs with no evidence of accumulation. The orally administered carbon-14 was almost completely excreted into urine and feces within 2 days after administration, and approximately 90% of the administered dose was excreted via urine. The major compound in excreta was clothianidin, accounting for >60% of the administered dose. The major metabolic reactions of clothianidin in rats were oxidative demethylation to form N-(2-chlorothiazol-5-ylmethyl)-N'-nitroguanidine and the cleavage of the carbon-nitrogen bond between the thiazolylmethyl moiety and the nitroguanidine moiety. The part of the molecule containing the nitroguanidine moiety was transformed mainly to N-methyl-N'-nitroguanidine, whereas the thiazol moiety was further metabolized to 2-(methylthio)thiazole-5-carboxylic acid. With the exception of the transiently delayed excretion of carbon-14 at the high-dose level, the rates of biokinetics, excretion, distribution, and metabolism of clothianidin were not markedly influenced by dose level and sex.

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

Determination and analysis of neutron flux distribution on radial Piercing beam port for utilization of Kartini research reactor

International Nuclear Information System (INIS)

Widarto

2002-01-01

Determination and analysis of neutron flux measurements on radial piercing beam port have been done as completion experimental data document and progressing on utilization of the Kartini research reactor purposes. The analysis and determination of the neutron flux have been carried out by using Au foils detector neutron activation analysis method which put on the radius of cross section (19 cm) and a long of radial piercing beam port (310 cm) Based on the calculation, distribution of the thermal neutron flux is around (8.3 ± 0.9) x 10 5 ncm -2 s -1 to (6.8 ± 0.5) x 10 7 ncm -2 s -1 and fast neutron is (5.0 ± 0.2) x 10 5 ncm -2 s -1 to (1.43 ± 0.6) x 10 7 ncm -2 s -1 . Analyzing by means of curve fitting method could be concluded that the neutron flux distribution on radial piercing beam port has profiled as a polynomial curve. (author)

Effect of feed flow pattern on the distribution of permeate fluxes in desalination by direct contact membrane distillation

KAUST Repository

Soukane, Sofiane

2017-05-31

The current study aims to highlight the effect of flow pattern on the variations of permeate fluxes over the membrane surface during desalination in a direct contact membrane distillation (DCMD) flat module. To do so, a three dimensional (3D) Computational Fluid Dynamics (CFD) model with embedded pore scale calculations is implemented to predict flow, heat and mass transfer in the DCMD module. Model validation is carried out in terms of average permeate fluxes with experimental data of seawater desalination using two commercially available PTFE membranes. Average permeate fluxes agree within 6% and less with experimental values without fitting parameters. Simulation results show that the distribution of permeate fluxes and seawater salinity over the membrane surface are strongly dependent on momentum and heat transport and that temperature and concentration polarization follow closely the flow distribution. The analysis reveals a drastic effect of recirculation loops and dead zones on module performance and recommendations to improve MD flat module design are drawn consequently.

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.

Fast flux module detection using matroid theory.

Science.gov (United States)

Reimers, Arne C; Bruggeman, Frank J; Olivier, Brett G; Stougie, Leen

2015-05-01

Flux balance analysis (FBA) is one of the most often applied methods on genome-scale metabolic networks. Although FBA uniquely determines the optimal yield, the pathway that achieves this is usually not unique. The analysis of the optimal-yield flux space has been an open challenge. Flux variability analysis is only capturing some properties of the flux space, while elementary mode analysis is intractable due to the enormous number of elementary modes. However, it has been found by Kelk et al. (2012) that the space of optimal-yield fluxes decomposes into flux modules. These decompositions allow a much easier but still comprehensive analysis of the optimal-yield flux space. Using the mathematical definition of module introduced by Müller and Bockmayr (2013b), we discovered useful connections to matroid theory, through which efficient algorithms enable us to compute the decomposition into modules in a few seconds for genome-scale networks. Using that every module can be represented by one reaction that represents its function, in this article, we also present a method that uses this decomposition to visualize the interplay of modules. We expect the new method to replace flux variability analysis in the pipelines for metabolic networks.

A transmission probability method for calculation of neutron flux distributions in hexagonal geometry

International Nuclear Information System (INIS)

Wasastjerna, F.; Lux, I.

1980-03-01

A transmission probability method implemented in the program TPHEX is described. This program was developed for the calculation of neutron flux distributions in hexagonal light water reactor fuel assemblies. The accuracy appears to be superior to diffusion theory, and the computation time is shorter than that of the collision probability method. (author)

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.

Distribution and metabolism of selenite and selenomethionine in the Japanese quail.

Science.gov (United States)

Anan, Yasumi; Ohbo, Ai; Tani, Yuta; Hatakeyama, Yoshiko; Yawata, Ayako; Ogra, Yasumitsu

2012-05-01

Compared to the many studies on the physiological and toxicological effects of selenium (Se) in mammals, avian Se metabolism is still an unexplored topic. Some birds are useful as poultry for human nutrition. Moreover, birds belong to higher trophic levels in the biosphere and thus may play an important role in Se circulation in the ecosystem in the same way as mammals do. In this study, we analyzed the distribution and metabolism of Se in an experimental bird, the Japanese quail, which was fed drinking water containing sodium selenite or selenomethionine (SeMet). The highest concentration of Se was detected in the pancreas, followed by down feathers, liver, and kidneys. SeMet was more efficiently incorporated into the quail than selenite. The specific and preferable distribution of Se to the high molecular weight fraction in the serum of the quail was observed only in the SeMet-ingestion group. As in mammals, selenosugar and trimethylselenonium were the major metabolites in quail excreta. Three unknown Se metabolites were detected by HPLC-ICP-MS. Although part of the metabolic pathway of Se in the Japanese quail fed selenite and SeMet was the same as that observed in mammals, the bird also showed certain avian-specific metabolic process for Se.

Critical heat fluxes and liquid distribution in annular channels in the dispersion-annular flow

International Nuclear Information System (INIS)

Boltenko, Eh.A.; Pomet'ko, R.S.

1984-01-01

On the basis of using the dependence of intensity of total mass transfer between the flux nucleus and wall film obtained for tubes with uniform heat release and taking into account the peculiarities of mass transfer between the flux nucleus and wall film in annular channels the technique for calculating the liquid distribution and critical capacity of annular channels with internal, external and bilateral heating at uniform and non-uniform heat release over the length is proposed. The calculation of annular channels critical capacity according to the suggested technique is performed. A satisfactory agreement of calculation results with the experimental data is attained

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

A benchmark analysis of radiation flux distribution for Boron Neutron Capture Therapy of canine brain tumors

Energy Technology Data Exchange (ETDEWEB)

Moran, Jean M. [Univ. of Idaho, Idaho Falls, ID (United States)

1992-02-01

Calculations of radiation flux and dose distributions for Boron Neutron Capture Therapy (BNCT) of brain tumors are typically performed using sophisticated three-dimensional analytical models based on either a homogeneous approximation or a simplified few-region approximation to the actual highly-heterogeneous geometry of the irradiation volume. Such models should be validated by comparison with calculations using detailed models in which all significant macroscopic tissue heterogeneities and geometric structures are explicitly represented as faithfully as possible. This work describes a validation exercise for BNCT of canine brain tumors. Geometric measurements of the canine anatomical structures of interest for this work were performed by dissecting and examining two essentially identical Labrador Retriever heads. Chemical analyses of various tissue samples taken during the dissections were conducted to obtain measurements of elemental compositions for tissues of interest. The resulting geometry and tissue composition data were then used to construct a detailed heterogeneous calculational model of the Labrador Retriever head. Calculations of three-dimensional radiation flux distributions pertinent to BNCT were performed for the model using the TORT discrete-ordinates radiation transport code. The calculations were repeated for a corresponding volume-weighted homogeneous tissue model. Comparison of the results showed that the peak neutron and photon flux magnitudes were quite similar for the two models (within 5%), but that the spatial flux profiles were shifted in the heterogeneous model such that the fluxes in some locations away from the peak differed from the corresponding fluxes in the homogeneous model by as much as 10-20%. Differences of this magnitude can be therapeutically significant, emphasizing the need for proper validation of simplified treatment planning models.

A benchmark analysis of radiation flux distribution for Boron Neutron Capture Therapy of canine brain tumors

International Nuclear Information System (INIS)

Moran, J.M.

1992-02-01

Calculations of radiation flux and dose distributions for Boron Neutron Capture Therapy (BNCT) of brain tumors are typically performed using sophisticated three-dimensional analytical models based on either a homogeneous approximation or a simplified few-region approximation to the actual highly-heterogeneous geometry of the irradiation volume. Such models should be validated by comparison with calculations using detailed models in which all significant macroscopic tissue heterogeneities and geometric structures are explicitly represented as faithfully as possible. This work describes a validation exercise for BNCT of canine brain tumors. Geometric measurements of the canine anatomical structures of interest for this work were performed by dissecting and examining two essentially identical Labrador Retriever heads. Chemical analyses of various tissue samples taken during the dissections were conducted to obtain measurements of elemental compositions for tissues of interest. The resulting geometry and tissue composition data were then used to construct a detailed heterogeneous calculational model of the Labrador Retriever head. Calculations of three-dimensional radiation flux distributions pertinent to BNCT were performed for the model using the TORT discrete-ordinates radiation transport code. The calculations were repeated for a corresponding volume-weighted homogeneous tissue model. Comparison of the results showed that the peak neutron and photon flux magnitudes were quite similar for the two models (within 5%), but that the spatial flux profiles were shifted in the heterogeneous model such that the fluxes in some locations away from the peak differed from the corresponding fluxes in the homogeneous model by as much as 10-20%. Differences of this magnitude can be therapeutically significant, emphasizing the need for proper validation of simplified treatment planning models

PERFORMANCE OPTIMIZATION OF LINEAR INDUCTION MOTOR BY EDDY CURRENT AND FLUX DENSITY DISTRIBUTION ANALYSIS

Directory of Open Access Journals (Sweden)

M. S. MANNA

2011-12-01

Full Text Available The development of electromagnetic devices as machines, transformers, heating devices confronts the engineers with several problems. For the design of an optimized geometry and the prediction of the operational behaviour an accurate knowledge of the dependencies of the field quantities inside the magnetic circuits is necessary. This paper provides the eddy current and core flux density distribution analysis in linear induction motor. Magnetic flux in the air gap of the Linear Induction Motor (LIM is reduced to various losses such as end effects, fringes, effect, skin effects etc. The finite element based software package COMSOL Multiphysics Inc. USA is used to get the reliable and accurate computational results for optimization the performance of Linear Induction Motor (LIM. The geometrical characteristics of LIM are varied to find the optimal point of thrust and minimum flux leakage during static and dynamic conditions.

Prompt neutrino fluxes in the atmosphere with PROSA parton distribution functions

International Nuclear Information System (INIS)

Garzelli, M.V.; Moch, S.; Placakyte, R.; Sigl, G.; Cooper-Sarkar, A.

2016-11-01

Effects on atmospheric prompt neutrino fluxes of present uncertainties affecting the nucleon composition are studied by using the PROSA fit to parton distribution functions (PDFs). The PROSA fit extends the precision of the PDFs to low x, which is the kinematic region of relevance for high-energy neutrino production, by taking into account LHCb data on charm and bottom hadroproduction. In the range of neutrino energies explored by present Very Large Volume Neutrino Telescopes, it is found that PDF uncertainties are far smaller with respect to those due to renormalization and factorization scale variation and to assumptions on the cosmic ray composition, which at present dominate and limit our knowledge of prompt neutrino fluxes. A discussion is presented on how these uncertainties affect the expected number of atmospheric prompt neutrino events in the analysis of high-energy events characterized by interaction vertices fully contained within the instrumented volume of the detector, performed by the IceCube collaboration.

Using a spatially-distributed hydrologic biogeochemistry model with nitrogen transport to study the spatial variation of carbon stocks and fluxes in a Critical Zone Observatory

Science.gov (United States)

Shi, Y.; Eissenstat, D. M.; He, Y.; Davis, K. J.

2017-12-01

Most current biogeochemical models are 1-D and represent one point in space. Therefore, they cannot resolve topographically driven land surface heterogeneity (e.g., lateral water flow, soil moisture, soil temperature, solar radiation) or the spatial pattern of nutrient availability. A spatially distributed forest biogeochemical model with nitrogen transport, Flux-PIHM-BGC, has been developed by coupling a 1-D mechanistic biogeochemical model Biome-BGC (BBGC) with a spatially distributed land surface hydrologic model, Flux-PIHM, and adding an advection dominated nitrogen transport module. Flux-PIHM is a coupled physically based model, which incorporates a land-surface scheme into the Penn State Integrated Hydrologic Model (PIHM). The land surface scheme is adapted from the Noah land surface model, and is augmented by adding a topographic solar radiation module. Flux-PIHM is able to represent the link between groundwater and the surface energy balance, as well as land surface heterogeneities caused by topography. In the coupled Flux-PIHM-BGC model, each Flux-PIHM model grid couples a 1-D BBGC model, while nitrogen is transported among model grids via surface and subsurface water flow. In each grid, Flux-PIHM provides BBGC with soil moisture, soil temperature, and solar radiation, while BBGC provides Flux-PIHM with spatially-distributed leaf area index. The coupled Flux-PIHM-BGC model has been implemented at the Susquehanna/Shale Hills Critical Zone Observatory. The model-predicted aboveground vegetation carbon and soil carbon distributions generally agree with the macro patterns observed within the watershed. The importance of abiotic variables (including soil moisture, soil temperature, solar radiation, and soil mineral nitrogen) in predicting aboveground carbon distribution is calculated using a random forest. The result suggests that the spatial pattern of aboveground carbon is controlled by the distribution of soil mineral nitrogen. A Flux-PIHM-BGC simulation

Measurement and analysis of neutron flux distribution of STACY heterogeneous core by position sensitive proportional counter. Contract research

Energy Technology Data Exchange (ETDEWEB)

Murazaki, Minoru; Uno, Yuichi; Miyoshi, Yoshinori [Japan Atomic Energy Research Inst., Tokai, Ibaraki (Japan). Tokai Research Establishment

2003-03-01

We have measured neutron flux distribution around the core tank of STACY heterogeneous core by position sensitive proportional counter (PSPC) to develop the method to measure reactivity for subcritical systems. The neutron flux distribution data in the position accuracy of {+-}13 mm have been obtained in the range of uranium concentration of 50g/L to 210g/L both in critical and in subcritical state. The prompt neutron decay constant, {alpha}, was evaluated from the measurement data of pulsed neutron source experiments. We also calculated distribution of neutron flux and {sup 3}He reaction rates at the location of PSPC by using continuous energy Monte Carlo code MCNP. The measurement data was compared with the calculation results. As results of comparison, calculated values agreed generally with measurement data of PSPC with Cd cover in the region above half of solution height, but the difference between calculated value and measurement data was large in the region below half of solution height. On the other hand, calculated value agreed well with measurement data of PSPC without Cd cover. (author)

Characterizing the Lyman-alpha forest flux probability distribution function using Legendre polynomials

Science.gov (United States)

Cieplak, Agnieszka; Slosar, Anze

2018-01-01

The Lyman-alpha forest has become a powerful cosmological probe at intermediate redshift. It is a highly non-linear field with much information present beyond the power spectrum. The flux probability flux distribution (PDF) in particular has been a successful probe of small scale physics. However, it is also sensitive to pixel noise, spectrum resolution, and continuum fitting, all of which lead to possible biased estimators. Here we argue that measuring the coefficients of the Legendre polynomial expansion of the PDF offers several advantages over measuring the binned values as is commonly done. Since the n-th Legendre coefficient can be expressed as a linear combination of the first n moments of the field, this allows for the coefficients to be measured in the presence of noise and allows for a clear route towards marginalization over the mean flux. Additionally, in the presence of noise, a finite number of these coefficients are well measured with a very sharp transition into noise dominance. This compresses the information into a small amount of well-measured quantities. Finally, we find that measuring fewer quasars with high signal-to-noise produces a higher amount of recoverable information.

Calculation of the radial and axial flux and power distribution for a CANDU 6 reactor with both the MCNP6 and Serpent codes

International Nuclear Information System (INIS)

Hussein, M.S.; Bonin, H.W.; Lewis, B.J.

2014-01-01

The most recent versions of the Monte Carlo-based probabilistic transport code MCNP6 and the continuous energy reactor physics burnup calculation code Serpent allow for a 3-D geometry calculation accounting for the detailed geometry without unit-cell homogenization. These two codes are used to calculate the axial and radial flux and power distributions for a CANDU6 GENTILLY-2 nuclear reactor core with 37-element fuel bundles. The multiplication factor, actual flux distribution and power density distribution were calculated by using a tally combination for MCNP6 and detector analysis for Serpent. Excellent agreement was found in the calculated flux and power distribution. The Serpent code is most efficient in terms of the computational time. (author)

Calculation of the radial and axial flux and power distribution for a CANDU 6 reactor with both the MCNP6 and Serpent codes

Energy Technology Data Exchange (ETDEWEB)

Hussein, M.S.; Bonin, H.W., E-mail: mohamed.hussein@rmc.ca, E-mail: bonin-h@rmc.ca [Royal Military College of Canada, Dept. of Chemistry and Chemical Engineering, Kingston, ON (Canada); Lewis, B.J., E-mail: Brent.Lewis@uoit.ca [Univ. of Ontario Inst. of Tech., Faculty of Energy Systems and Nuclear Science, Oshawa, ON (Canada)

2014-07-01

The most recent versions of the Monte Carlo-based probabilistic transport code MCNP6 and the continuous energy reactor physics burnup calculation code Serpent allow for a 3-D geometry calculation accounting for the detailed geometry without unit-cell homogenization. These two codes are used to calculate the axial and radial flux and power distributions for a CANDU6 GENTILLY-2 nuclear reactor core with 37-element fuel bundles. The multiplication factor, actual flux distribution and power density distribution were calculated by using a tally combination for MCNP6 and detector analysis for Serpent. Excellent agreement was found in the calculated flux and power distribution. The Serpent code is most efficient in terms of the computational time. (author)

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.

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

Determination of neutron flux distribution in an Am-Be irradiator using the MCNP.

Science.gov (United States)

Shtejer-Diaz, K; Zamboni, C B; Zahn, G S; Zevallos-Chávez, J Y

2003-10-01

A neutron irradiator has been assembled at IPEN facilities to perform qualitative-quantitative analysis of many materials using thermal and fast neutrons outside the nuclear reactor premises. To establish the prototype specifications, the neutron flux distribution and the absorbed dose rates were calculated using the MCNP computer code. These theoretical predictions then allow one to discuss the optimum irradiator design and its performance.

Inverse Estimation of Heat Flux and Temperature Distribution in 3D Finite Domain

International Nuclear Information System (INIS)

Muhammad, Nauman Malik

2009-02-01

Inverse heat conduction problems occur in many theoretical and practical applications where it is difficult or practically impossible to measure the input heat flux and the temperature of the layer conducting the heat flux to the body. Thus it becomes imperative to devise some means to cater for such a problem and estimate the heat flux inversely. Adaptive State Estimator is one such technique which works by incorporating the semi-Markovian concept into a Bayesian estimation technique thereby developing an inverse input and state estimator consisting of a bank of parallel adaptively weighted Kalman filters. The problem presented in this study deals with a three dimensional system of a cube with one end conducting heat flux and all the other sides are insulated while the temperatures are measured on the accessible faces of the cube. The measurements taken on these accessible faces are fed into the estimation algorithm and the input heat flux and the temperature distribution at each point in the system is calculated. A variety of input heat flux scenarios have been examined to underwrite the robustness of the estimation algorithm and hence insure its usability in practical applications. These include sinusoidal input flux, a combination of rectangular, linearly changing and sinusoidal input flux and finally a step changing input flux. The estimator's performance limitations have been examined in these input set-ups and error associated with each set-up is compared to conclude the realistic application of the estimation algorithm in such scenarios. Different sensor arrangements, that is different sensor numbers and their locations are also examined to impress upon the importance of number of measurements and their location i.e. close or farther from the input area. Since practically it is both economically and physically tedious to install more number of measurement sensors, hence optimized number and location is very important to determine for making the study more

Distribution of flux vacua around singular points in Calabi-Yau moduli space

International Nuclear Information System (INIS)

Eguchi, Tohru; Tachikawa, Yuji

2006-01-01

We study the distribution of type-IIB flux vacua in the moduli space near various singular loci, e.g. conifolds, ADE singularities on P 1 , Argyres-Douglas point etc, using the Ashok-Douglas density det (R+ω). We find that the vacuum density is integrable around each of them, irrespective of the type of the singularities. We study in detail an explicit example of an Argyres-Douglas point embedded in a compact Calabi-Yau manifold

Detrimental and protective fat: body fat distribution and its relation to metabolic disease.

Science.gov (United States)

Booth, Andrea; Magnuson, Aaron; Foster, Michelle

2014-01-01

Obesity is linked to numerous comorbidities that include, but are not limited to, glucose intolerance, insulin resistance, dyslipidemia, and cardiovascular disease. Current evidence suggests, however, obesity itself is not an exclusive predictor of metabolic dysregulation but rather adipose tissue distribution. Obesity-related adverse health consequences occur predominately in individuals with upper body fat accumulation, the detrimental distribution, commonly associated with visceral obesity. Increased lower body subcutaneous adipose tissue, however, is associated with a reduced risk of obesity-induced metabolic dysregulation and even enhanced insulin sensitivity, thus, storage in this region is considered protective. The proposed mechanisms that causally relate the differential outcomes of adipose tissue distribution are often attributed to location and/or adipocyte regulation. Visceral adipose tissue effluent to the portal vein drains into the liver where hepatocytes are directly exposed to its metabolites and secretory products, whereas the subcutaneous adipose tissue drains systemically. Adipose depots are also inherently different in numerous ways such as adipokine release, immunity response and regulation, lipid turnover, rate of cell growth and death, and response to stress and sex hormones. Proximal extrinsic factors also play a role in the differential drive between adipose tissue depots. This review focuses on the deleterious mechanisms postulated to drive the differential metabolic response between central and lower body adipose tissue distribution.

Inverse heat transfer analysis of a functionally graded fin to estimate time-dependent base heat flux and temperature distributions

International Nuclear Information System (INIS)

Lee, Haw-Long; Chang, Win-Jin; Chen, Wen-Lih; Yang, Yu-Ching

2012-01-01

Highlights: ► Time-dependent base heat flux of a functionally graded fin is inversely estimated. ► An inverse algorithm based on the conjugate gradient method and the discrepancy principle is applied. ► The distributions of temperature in the fin are determined as well. ► The influence of measurement error and measurement location upon the precision of the estimated results is also investigated. - Abstract: In this study, an inverse algorithm based on the conjugate gradient method and the discrepancy principle is applied to estimate the unknown time-dependent base heat flux of a functionally graded fin from the knowledge of temperature measurements taken within the fin. Subsequently, the distributions of temperature in the fin can be determined as well. It is assumed that no prior information is available on the functional form of the unknown base heat flux; hence the procedure is classified as the function estimation in inverse calculation. The temperature data obtained from the direct problem are used to simulate the temperature measurements. The influence of measurement errors and measurement location upon the precision of the estimated results is also investigated. Results show that an excellent estimation on the time-dependent base heat flux and temperature distributions can be obtained for the test case considered in this study.

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

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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

Four energy group neutron flux distribution in the Syrian miniature neutron source reactor using the WIMSD4 and CITATION code

International Nuclear Information System (INIS)

Khattab, K.; Omar, H.; Ghazi, N.

2009-01-01

A 3-D (R, θ , Z) neutronic model for the Miniature Neutron Source Reactor (MNSR) was developed earlier to conduct the reactor neutronic analysis. The group constants for all the reactor components were generated using the WIMSD4 code. The reactor excess reactivity and the four group neutron flux distributions were calculated using the CITATION code. This model is used in this paper to calculate the point wise four energy group neutron flux distributions in the MNSR versus the radius, angle and reactor axial directions. Good agreement is noticed between the measured and the calculated thermal neutron flux in the inner and the outer irradiation site with relative difference less than 7% and 5% respectively. (author)

Central carbon metabolism influences cellulase production in Bacillus licheniformis.

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Wang, J; Liu, S; Li, Y; Wang, H; Xiao, S; Li, C; Liu, B

2018-01-01

Bacillus licheniformis that can produce cellulase including endo glucanase and glucosidase is an important industrial microbe for cellulose degradation. The purpose of this research was to assess the effect of endo glucanase gene bglC and glucosidase gene bglH on the central metabolic flux in B. licheniformis. bglC and bglH were knocked out using homologous recombination method, respectively, and the corresponding knockout strains were obtained for 13 C metabolic flux analysis. A significant change was observed in metabolic fluxes after 13 C metabolic flux ratio analysis. In both of the knockout strains, the increased fluxes of the pentose phosphate pathway and malic enzyme reaction enabled an elevated supply of NADPH which provided enough reducing power for the in vivo synthesis reactions. The fluxes through tricarboxylic acid cycle and anaplerotic reactions increased fast in the two knockout strains, which meant more energy generated. The changed fluxes in central carbon metabolism provided a holistic view of the physiological status in B. licheniformis and possible targets for further strain engineering. Cellulase is very important in the field of agriculture and bioenergy because of its degrading effect on cellulosic biomass. This study presented the effect of central carbon metabolism on cellulase production in Bacillus licheniformis. The study also provided a holistic view of the physiological status in B. licheniformis. The shifted metabolism provided a quantitative evaluation of the biosynthesis of cellulase and a priority ranked target list for further strain engineering. © 2017 The Society for Applied Microbiology.

k-OptForce: integrating kinetics with flux balance analysis for strain design.

Directory of Open Access Journals (Sweden)

Anupam Chowdhury

2014-02-01

Full Text Available Computational strain design protocols aim at the system-wide identification of intervention strategies for the enhanced production of biochemicals in microorganisms. Existing approaches relying solely on stoichiometry and rudimentary constraint-based regulation overlook the effects of metabolite concentrations and substrate-level enzyme regulation while identifying metabolic interventions. In this paper, we introduce k-OptForce, which integrates the available kinetic descriptions of metabolic steps with stoichiometric models to sharpen the prediction of intervention strategies for improving the bio-production of a chemical of interest. It enables identification of a minimal set of interventions comprised of both enzymatic parameter changes (for reactions with available kinetics and reaction flux changes (for reactions with only stoichiometric information. Application of k-OptForce to the overproduction of L-serine in E. coli and triacetic acid lactone (TAL in S. cerevisiae revealed that the identified interventions tend to cause less dramatic rearrangements of the flux distribution so as not to violate concentration bounds. In some cases the incorporation of kinetic information leads to the need for additional interventions as kinetic expressions render stoichiometry-only derived interventions infeasible by violating concentration bounds, whereas in other cases the kinetic expressions impart flux changes that favor the overproduction of the target product thereby requiring fewer direct interventions. A sensitivity analysis on metabolite concentrations shows that the required number of interventions can be significantly affected by changing the imposed bounds on metabolite concentrations. Furthermore, k-OptForce was capable of finding non-intuitive interventions aiming at alleviating the substrate-level inhibition of key enzymes in order to enhance the flux towards the product of interest, which cannot be captured by stoichiometry-alone analysis

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.

Modeling Lactococcus lactis using a genome-scale flux model

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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.

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.

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.

Fieldable computer system for determining gamma-ray pulse-height distributions, flux spectra, and dose rates from Little Boy

International Nuclear Information System (INIS)

Moss, C.E.; Lucas, M.C.; Tisinger, E.W.; Hamm, M.E.

1984-01-01

Our system consists of a LeCroy 3500 data acquisition system with a built-in CAMAC crate and eight bismuth-germanate detectors 7.62 cm in diameter and 7.62 cm long. Gamma-ray pulse-height distributions are acquired simultaneously for up to eight positions. The system was very carefully calibrated and characterized from 0.1 to 8.3 MeV using gamma-ray spectra from a variety of radioactive sources. By fitting the pulse-height distributions from the sources with a function containing 17 parameters, we determined theoretical repsonse functions. We use these response functions to unfold the distributions to obtain flux spectra. A flux-to-dose-rate conversion curve based on the work of Dimbylow and Francis is then used to obtain dose rates. Direct use of measured spectra and flux-to-dose-rate curves to obtain dose rates avoids the errors that can arise from spectrum dependence in simple gamma-ray dosimeter instruments. We present some gamma-ray doses for the Little Boy assembly operated at low power. These results can be used to determine the exposures of the Hiroshima survivors and thus aid in the establishment of radation exposure limits for the nuclear industry

Experimental data on heat flux distribution from a volumetrically heated pool with frozen boundaries

International Nuclear Information System (INIS)

Helle, Maria; Kymaelaeinen, Olli; Tuomisto, Harri

1999-01-01

The COPO II experiments are confirmatory experiments and a continuation project to the earlier COPO I experiments. As in COPO 1, a molten corium pool on the lower head of a RPV is simulated by a two - dimensional slice of it in linear scale 1:2. The corium is simulated by water-zinc sulfate solution with volumetric Joule heating. The heat flux distribution on the boundaries and the temperature distribution in the pool are measured. The major new feature in COPO II is the cooling arrangement which is based on circulation of liquid nitrogen on the outside of the pool boundaries. The use of liquid nitrogen leads to formation of ice on the inside of boundaries. Two geometrically different versions of the COPO II facility have been constructed: one with a tori-spherical bottom shape, simulating the RPV of a VVER-440 reactor as COPO I, and another one with semicircular bottom simulating a western PWR such as AP600. The modified Rayleigh number in the COPO II experiments corresponds to the one in a prototypic corium pool (∼ 10 15 ). This paper reports results from the COPO II-Lo and COPO II-AP experiments with homogenous pool. Results indicate that the upward heat fluxes are in agreement with the results of the COPO I experiments. Also, as expected, the time averaged upward heat flux profile was relatively flat. On the other hand, the heat fluxes at the side and bottom boundaries of the pool were slightly higher in COPO II-Lo than in COPO I. In COPO II-AP, the average heat transfer coefficients to the curved boundary were higher than predicted by Jahn's and Mayinger's correlation, but slightly lower than in BALI experiments. (authors)

Measurement of thermal neutron distribution of flux in the fuel element cluster - Progress report

International Nuclear Information System (INIS)

Krcevinac, S.B.; Takac, S.M.

1966-12-01

Relative distribution of thermal neutron flux in the fuel element cluster (19 UO 2 rods with Zr-II cladding, D 2 O moderator and coolant) was measured by newly developed cell perturbation method. The obtained values of mean density ratios are compared to the results obtained by TER-I code using Amouyal - Benoist model [sr

Flux distribution in phantom for biomedical use of beam-type thermal neutrons

International Nuclear Information System (INIS)

Aoki, Kazuhiko; Kobayashi, Tooru; Kanda, Keiji; Kimura, Itsuro

1985-01-01

For boron neutron capture therapy, the thermal neutron beam is worth using as therapeutic neutron irradiation without useless and unfavorable exposure of normal tissues around tumor and for microanalysis system to measure ppm-order 10 B concentrations in tissue and to search for the location of the metastasis of tumor. In the present study, the thermal neutron flux distribution in a phantom, when beam-type thermal neutrons were incident on it, was measured at the KUR Neutron Guide Tube. The measurements were carried out by two different methods using indium foil. The one is an ordinary foil activation technique by using the 115 In(n, γ) 116m 1 In reactions, while the other is to detect γ-rays from the 115 In(n, γ) 116m 2 In reactions during neutron irradiations with a handy-type Ge detector. The calculations with DOT 3.5 were performed to examine thermal neutron flux in the phantom for various beam size and phantom size. The experimental and calculated results are in good agreement and it is shown that the second type measurement has a potential for practical application as a new monitoring system of the thermal neutron flux in a living body for boron neutron capture therapy. (author)

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.

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.

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

The Crc/CrcZ-CrcY global regulatory system helps the integration of gluconeogenic and glycolytic metabolism in Pseudomonas putida.

Science.gov (United States)

La Rosa, Ruggero; Nogales, Juan; Rojo, Fernando

2015-09-01

In metabolically versatile bacteria, carbon catabolite repression (CCR) facilitates the preferential assimilation of the most efficient carbon sources, improving growth rates and fitness. In Pseudomonas putida, the Crc and Hfq proteins and the CrcZ and CrcY small RNAs, which are believed to antagonize Crc/Hfq, are key players in CCR. Unlike that seen in other bacterial species, succinate and glucose elicit weak CCR in this bacterium. In the present work, metabolic, transcriptomic and constraint-based metabolic flux analyses were combined to clarify whether P. putida prefers succinate or glucose, and to identify the role of the Crc protein in the metabolism of these compounds. When provided simultaneously, succinate was consumed faster than glucose, although both compounds were metabolized. CrcZ and CrcY levels were lower when both substrates were present than when only one was provided, suggesting a role for Crc in coordinating metabolism of these compounds. Flux distribution analysis suggested that, when both substrates are present, Crc works to organize a metabolism in which carbon compounds flow in opposite directions: from glucose to pyruvate, and from succinate to pyruvate. Thus, our results support that Crc not only favours the assimilation of preferred compounds, but balances carbon fluxes, optimizing metabolism and growth. © 2015 Society for Applied Microbiology and John Wiley & Sons Ltd.

Methane fluxes during the cold season: distribution and mass transfer in the snow cover of bogs

Science.gov (United States)

Smagin, A. V.; Shnyrev, N. A.

2015-08-01

Fluxes and profile distribution of methane in the snow cover and different landscape elements of an oligotrophic West-Siberian bog (Mukhrino Research Station, Khanty-Mansiisk autonomous district) have been studied during a cold season. Simple models have been proposed for the description of methane distribution in the inert snow layer, which combine the transport of the gas and a source of constant intensity on the soil surface. The formation rates of stationary methane profiles in the snow cover have been estimated (characteristic time of 24 h). Theoretical equations have been derived for the calculation of small emission fluxes from bogs to the atmosphere on the basis of the stationary profile distribution parameters, the snow porosity, and the effective methane diffusion coefficient in the snow layer. The calculated values of methane emission significantly (by 2-3 to several tens of times) have exceeded the values measured under field conditions by the closed chamber method (0.008-0.25 mg C/(m2 h)), which indicates the possibility of underestimating the contribution of the cold period to the annual emission cycle of bog methane.

Measurement of angular distribution of neutron flux for the 6 MeV race-track microtron based pulsed neutron source

Energy Technology Data Exchange (ETDEWEB)

Patil, B.J., E-mail: bjp@physics.unipune.ernet.i [Department of Physics, University of Pune, Pune 411 007 (India); Chavan, S.T.; Pethe, S.N.; Krishnan, R. [SAMEER, IIT Powai Campus, Mumbai 400 076 (India); Dhole, S.D., E-mail: sanjay@physics.unipune.ernet.i [Department of Physics, University of Pune, Pune 411 007 (India)

2010-09-15

The 6 MeV race track microtron based pulsed neutron source has been designed specifically for the elemental analysis of short lived activation products, where the low neutron flux requirement is desirable. Electrons impinges on a e-{gamma} target to generate bremsstrahlung radiations, which further produces neutrons by photonuclear reaction in {gamma}-n target. The optimisation of these targets along with their spectra were estimated using FLUKA code. The measurement of neutron flux was carried out by activation of vanadium at different scattering angles. Angular distribution of neutron flux indicates that the flux decreases with increase in the angle and are in good agreement with the FLUKA simulation.

Complex interactions between dietary and genetic factors impact lycopene metabolism and distribution

Science.gov (United States)

Moran, Nancy E.; Erdman, John W.; Clinton, Steven K.

2013-01-01

Intake of lycopene, a red, tetraterpene carotenoid found in tomatoes is epidemiologically associated with a decreased risk of chronic disease processes, and lycopene has demonstrated bioactivity in numerous in vitro and animal models. However, our understanding of absorption, tissue distribution, and biological impact in humans remains very limited. Lycopene absorption is strongly impacted by dietary composition, especially the amount of fat. Concentrations of circulating lycopene in lipoproteins may be further influenced by a number of variations in genes related to lipid absorption and metabolism. Lycopene is not uniformly distributed among tissues, with adipose, liver, and blood being the major body pools, while the testes, adrenals, and liver have the greatest concentrations compared to other organs. Tissue concentrations of lycopene are likely dictated by expression of and genetic variation in lipoprotein receptors, cholesterol transporters, and carotenoid metabolizing enzymes, thus impacting lycopene accumulation at target sites of action. The novel application of genetic evaluation in concert with lycopene tracers will allow determination of which genes and polymorphisms define individual lycopene metabolic phenotypes, response to dietary variables, and ultimately determine biological and clinical outcomes. A better understanding of the relationship between diet, genetics, and lycopene distribution will provide necessary information to interpret epidemiological findings more accurately and to design effective, personalized clinical nutritional interventions addressing hypotheses regarding health outcomes. PMID:23845854

A DETERMINATION OF THE FLUX DENSITY IN CORE OF DISTRIBUTION TRANSFORMERS, WHAT BUILT WITH THE COMMON USING OF GRAIN AND NON GRAIN ORIENTED MAGNETIC STEELS

Directory of Open Access Journals (Sweden)

I.V. Pentegov

2015-12-01

Full Text Available Purpose. The development of calculation method to determinate the flux densities in different parts of the magnetic cores of distribution transformers, what built from different types magnetic steel (mixed core. Methodology. The method is based on the scientific positions of Theoretical Electrical Engineering – the theory of the electromagnetic field in nonlinear mediums to determine the distribution of magnetic flux in mixed core of transformer, what are using different types of steel what have the different magnetic properties. Results. The developed method gives possible to make calculation of the flux density and influence of skin effect in different parts of the magnetic cores of distribution transformer, where are used mix of grain oriented (GO and non grain oriented (NGO steels. Was determinate the general basic conditions for the calculation of flux density in the laminations from grain and non grain oriented steels of the magnetic core: the strength of magnetic field for the laminations of particular part of mixed core is the same; the sum of the magnetic fluxes in GO and NGO steels in particular part of mixed core is equal with the designed magnetic flux in this part of mixed core. Discover, the magnetic flux in mixed core of the transformer has specific distribution between magnetic steels. The flux density is higher in laminations from GO steel and smaller in laminations from the NGO steel. That is happened because for magnetic flux is easier pass through laminations from GO steel, what has better magnetic conductance than laminations from NGO steel. Originality. The common using of different types of magnetic steels in cores for distribution transformers gives possibility to make design of transformer with low level of no load losses, high efficiency and with optimal cost. Practical value. The determination of the flux density in different parts of magnetic core with GO and NGO steels gives possibility make accurate calculation of

Analysis of Neutron Flux Distribution in Rsg-Gas Reactor With U-Mo Fuels

Directory of Open Access Journals (Sweden)

Taswanda Taryo

2004-01-01

Full Text Available The use of U-Mo fuels in research reactors seems to be promising and, recently, world researchers have carried out these such activities actively. The National Nuclear Energy Agency (BATAN which owns RSG-GAS reactor available in Serpong Research Center for Atomic Energy should anticipate this trend. It is, therefore, this research work on the use of U-Mo fuels in RSG-GAS reactor should be carried out. The work was focused on the analysis of neutron flux distribution in the RSG-GAS reactor using different content of molybdenum in U-Mo fuels. To begin with, RSG-GAS reactor core model was developed and simulated into X, Y and Z dimensions. Cross section of materials based on the developed cells of standard and control fuels was then generated using WIMS-D5-B. The criticality calculations were finally carried out applying BATAN-2DIFF code. The results showed that the neutron flux distribution obtained in U-Mo-fuel-based RSG-GAS core is very similar to those achieved in the 300-gram sillicide-fuel-based RSG-GAS reactor core. Indeed, the utilization of the U-Mo RSG-GAS core can be very similar to that of the high-density sillicide reactor core and even could be better in the future.

Cyanobacterial carbon metabolism: Fluxome plasticity and oxygen dependence: Cyanobacterial Carbon Metabolism

Energy Technology Data Exchange (ETDEWEB)

Wan, Ni [Washington Univ., St. Louis, MO (United States); DeLorenzo, Drew M. [Washington Univ., St. Louis, MO (United States); He, Lian [Washington Univ., St. Louis, MO (United States); You, Le [Washington Univ., St. Louis, MO (United States); Immethun, Cheryl M. [Washington Univ., St. Louis, MO (United States); Wang, George [Joint BioEnergy Inst. (JBEI), Emeryville, CA (United States); Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Baidoo, Edward E. K. [Joint BioEnergy Inst. (JBEI), Emeryville, CA (United States); Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Hollinshead, Whitney [Washington Univ., St. Louis, MO (United States); Keasling, Jay D. [Joint BioEnergy Inst. (JBEI), Emeryville, CA (United States); Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Univ. of California, Berkeley, CA (United States); Technical Univ. of Denmark, Lyngby (Denmark); Moon, Tae Seok [Department of Energy, Environmental and Chemical Engineering, Washington University in St. Louis, St. Louis Missouri 63130; Tang, Yinjie J. [Washington Univ., St. Louis, MO (United States)

2017-03-30

Synechocystis sp. strain PCC 6803 has been widely used as a photo-biorefinery chassis. Based on its genome annotation, this species contains a complete TCA cycle, an Embden-Meyerhof-Parnas pathway (EMPP), an oxidative pentose phosphate pathway (OPPP), and an Entner–Doudoroff pathway (EDP). To evaluate how Synechocystis 6803 catabolizes glucose under heterotrophic conditions, we performed ¹³C metabolic flux analysis, metabolite pool size analysis, gene knockouts, and heterologous expressions. The results revealed a cyclic mode of flux through the OPPP. Small, but non-zero, fluxes were observed through the TCA cycle and the malic shunt. Independent knockouts of 6-phosphogluconate dehydrogenase (gnd) and malic enzyme (me) corroborated these results, as neither mutant could grow under dark heterotrophic conditions. Our data also indicate that Synechocystis 6803 metabolism relies upon oxidative phosphorylation to generate ATP from NADPH under dark or insufficient light conditions. The pool sizes of intermediates in the TCA cycle, particularly acetyl-CoA, were found to be several fold lower in Synechocystis 6803 (compared to E. coli metabolite pool sizes), while its sugar phosphate intermediates were several-fold higher. Moreover, negligible flux was detected through the native, or heterologous, EDP in the wild type or Δgnd strains under heterotrophic conditions. Comparing photoautotrophic, photomixotrophic, and heterotrophic conditions, the Calvin cycle, OPPP, and EMPP in Synechocystis 6803 possess the ability to regulate their fluxes under various growth conditions (plastic), whereas its TCA cycle always maintains at low levels (rigid). This work also demonstrates how genetic profiles do not always reflect actual metabolic flux through native or heterologous pathways. Biotechnol. Bioeng. 2017;114: 1593–1602. © 2017 Wiley Periodicals, Inc.

Flux distribution by neutrons semi-conductors detectors during the startup of the EL4 reactor

International Nuclear Information System (INIS)

Fuster, S.; Tarabella, A.

1967-01-01

The Cea developed neutron semi-conductors detectors which allows a quasi-instantaneous monitoring of neutrons flux distribution, when placed in a reactor during the tests. These detectors have been experimented in the EL4 reactor. The experiment and the results are presented and compared with reference mappings. (A.L.B.)

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.

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

SMALL-SCALE AND GLOBAL DYNAMOS AND THE AREA AND FLUX DISTRIBUTIONS OF ACTIVE REGIONS, SUNSPOT GROUPS, AND SUNSPOTS: A MULTI-DATABASE STUDY

Energy Technology Data Exchange (ETDEWEB)

Muñoz-Jaramillo, Andrés; Windmueller, John C.; Amouzou, Ernest C.; Longcope, Dana W. [Department of Physics, Montana State University, Bozeman, MT 59717 (United States); Senkpeil, Ryan R. [Department of Physics, Purdue University, West Lafayette, IN 47907 (United States); Tlatov, Andrey G. [Kislovodsk Mountain Astronomical Station of the Pulkovo Observatory, Kislovodsk 357700 (Russian Federation); Nagovitsyn, Yury A. [Pulkovo Astronomical Observatory, Russian Academy of Sciences, St. Petersburg 196140 (Russian Federation); Pevtsov, Alexei A. [National Solar Observatory, Sunspot, NM 88349 (United States); Chapman, Gary A.; Cookson, Angela M. [San Fernando Observatory, Department of Physics and Astronomy, California State University Northridge, Northridge, CA 91330 (United States); Yeates, Anthony R. [Department of Mathematical Sciences, Durham University, South Road, Durham DH1 3LE (United Kingdom); Watson, Fraser T. [National Solar Observatory, Tucson, AZ 85719 (United States); Balmaceda, Laura A. [Institute for Astronomical, Terrestrial and Space Sciences (ICATE-CONICET), San Juan (Argentina); DeLuca, Edward E. [Harvard-Smithsonian Center for Astrophysics, Cambridge, MA 02138 (United States); Martens, Petrus C. H., E-mail: munoz@solar.physics.montana.edu [Department of Physics and Astronomy, Georgia State University, Atlanta, GA 30303 (United States)

2015-02-10

In this work, we take advantage of 11 different sunspot group, sunspot, and active region databases to characterize the area and flux distributions of photospheric magnetic structures. We find that, when taken separately, different databases are better fitted by different distributions (as has been reported previously in the literature). However, we find that all our databases can be reconciled by the simple application of a proportionality constant, and that, in reality, different databases are sampling different parts of a composite distribution. This composite distribution is made up by linear combination of Weibull and log-normal distributions—where a pure Weibull (log-normal) characterizes the distribution of structures with fluxes below (above) 10{sup 21}Mx (10{sup 22}Mx). Additionally, we demonstrate that the Weibull distribution shows the expected linear behavior of a power-law distribution (when extended to smaller fluxes), making our results compatible with the results of Parnell et al. We propose that this is evidence of two separate mechanisms giving rise to visible structures on the photosphere: one directly connected to the global component of the dynamo (and the generation of bipolar active regions), and the other with the small-scale component of the dynamo (and the fragmentation of magnetic structures due to their interaction with turbulent convection)

Satellite-Derived Distributions, Inventories and Fluxes of Dissolved and Particulate Organic Matter Along the Northeastern U.S. Continental Margin

Science.gov (United States)

Mannino, A.; Hooker, S. B.; Hyde, K.; Novak, M. G.; Pan, X.; Friedrichs, M.; Cahill, B.; Wilkin, J.

2011-01-01

Estuaries and the coastal ocean experience a high degree of variability in the composition and concentration of particulate and dissolved organic matter (DOM) as a consequence of riverine and estuarine fluxes of terrigenous DOM, sediments, detritus and nutrients into coastal waters and associated phytoplankton blooms. Our approach integrates biogeochemical measurements, optical properties and remote sensing to examine the distributions and inventories of organic carbon in the U.S. Middle Atlantic Bight and Gulf of Maine. Algorithms developed to retrieve colored DOM (CDOM), Dissolved (DOC) and Particulate Organic Carbon (POC) from NASA's MODIS-Aqua and SeaWiFS satellite sensors are applied to quantify the distributions and inventories of DOC and POC. Horizontal fluxes of DOC and POC from the continental margin to the open ocean are estimated from SeaWiFS and MODIS-Aqua distributions of DOC and POC and horizontal divergence fluxes obtained from the Northeastern North Atlantic ROMS model. SeaWiFS and MODIS imagery reveal the importance of estuarine outflow to the export of CDOM and DOC to the coastal ocean and a net community production of DOC on the shelf.

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.

Second Law of Thermodynamics Applied to Metabolic Networks

Science.gov (United States)

Nigam, R.; Liang, S.

2003-01-01

We present a simple algorithm based on linear programming, that combines Kirchoff's flux and potential laws and applies them to metabolic networks to predict thermodynamically feasible reaction fluxes. These law's represent mass conservation and energy feasibility that are widely used in electrical circuit analysis. Formulating the Kirchoff's potential law around a reaction loop in terms of the null space of the stoichiometric matrix leads to a simple representation of the law of entropy that can be readily incorporated into the traditional flux balance analysis without resorting to non-linear optimization. Our technique is new as it can easily check the fluxes got by applying flux balance analysis for thermodynamic feasibility and modify them if they are infeasible so that they satisfy the law of entropy. We illustrate our method by applying it to the network dealing with the central metabolism of Escherichia coli. Due to its simplicity this algorithm will be useful in studying large scale complex metabolic networks in the cell of different organisms.

Characterizing the Lyα forest flux probability distribution function using Legendre polynomials

Energy Technology Data Exchange (ETDEWEB)

Cieplak, Agnieszka M.; Slosar, Anže, E-mail: acieplak@bnl.gov, E-mail: anze@bnl.gov [Brookhaven National Laboratory, Bldg 510, Upton, NY, 11973 (United States)

2017-10-01

The Lyman-α forest is a highly non-linear field with considerable information available in the data beyond the power spectrum. The flux probability distribution function (PDF) has been used as a successful probe of small-scale physics. In this paper we argue that measuring coefficients of the Legendre polynomial expansion of the PDF offers several advantages over measuring the binned values as is commonly done. In particular, the n -th Legendre coefficient can be expressed as a linear combination of the first n moments, allowing these coefficients to be measured in the presence of noise and allowing a clear route for marginalisation over mean flux. Moreover, in the presence of noise, our numerical work shows that a finite number of coefficients are well measured with a very sharp transition into noise dominance. This compresses the available information into a small number of well-measured quantities. We find that the amount of recoverable information is a very non-linear function of spectral noise that strongly favors fewer quasars measured at better signal to noise.

Characterizing the Lyα forest flux probability distribution function using Legendre polynomials

Science.gov (United States)

Cieplak, Agnieszka M.; Slosar, Anže

2017-10-01

The Lyman-α forest is a highly non-linear field with considerable information available in the data beyond the power spectrum. The flux probability distribution function (PDF) has been used as a successful probe of small-scale physics. In this paper we argue that measuring coefficients of the Legendre polynomial expansion of the PDF offers several advantages over measuring the binned values as is commonly done. In particular, the n-th Legendre coefficient can be expressed as a linear combination of the first n moments, allowing these coefficients to be measured in the presence of noise and allowing a clear route for marginalisation over mean flux. Moreover, in the presence of noise, our numerical work shows that a finite number of coefficients are well measured with a very sharp transition into noise dominance. This compresses the available information into a small number of well-measured quantities. We find that the amount of recoverable information is a very non-linear function of spectral noise that strongly favors fewer quasars measured at better signal to noise.

Quantitative evaluation of respiration induced metabolic oscillations in erythrocytes

DEFF Research Database (Denmark)

Hald, Bjørn; Madsen, Mads F; Danø, Sune

2009-01-01

The changes in the partial pressures of oxygen and carbon dioxide (P(O(2)) and P(CO(2))) during blood circulation alter erythrocyte metabolism, hereby causing flux changes between oxygenated and deoxygenated blood. In the study we have modeled this effect by extending the comprehensive kinetic...... model by Mulquiney and Kuchel [P.J. Mulquiney, and P.W. Kuchel. Model of 2,3-bisphosphoglycerate metabolism in the human erythrocyte based on detailed enzyme kinetic equations: equations and parameter refinement, Biochem. J. 1999, 342, 581-596.] with a kinetic model of hemoglobin oxy...... solely by steady state consideration. The metabolic system exhibits a broad distribution of time scales. Relaxations of modes with hemoglobin and Mg(2+) binding reactions are very fast, while modes involving glycolytic, membrane transport and 2,3-BPG shunt reactions are much slower. Incomplete slow mode...

Calculation of neutron flux distribution of thermal neutrons from microtron converter in a graphite moderator with water reflector

International Nuclear Information System (INIS)

Andrejsek, K.

1977-01-01

The calculation is made of the thermal neutron flux in the moderator and reflector by solving the neutron diffusion equation using the four-group theory. The correction for neutron absorption in the moderator was carried out using the perturbation theory. The calculation was carried out for four groups with the following energy ranges: the first group 2 MeV to 3 keV, the second group 3 keV to 5 eV, the third group 5 eV to 0.025 eV and the fourth group 0.025 eV. The values of the macroscopic cross section of capture and scattering, of the diffusion coefficient, the macroscopic cross section of the moderator, of the neutron age and the extrapolation length for the water-graphite moderator used in the calculations are given. The spatial distribution of the thermal neutron flux is graphically represented for graphite of a 30, 40, and 50 cm radius and for graphite of a 30 and 40 cm radius with a 10 cm water reflector; a graphic comparison is made of the distribution of the thermal neutron flux in water and in graphite, both 40 cm in radius. The system of graphite with reflector proved to be the best and most efficient system for raising the flux density of thermal neutrons. (J.P.)

Regional patterns of labile organic carbon flux in North American Arctic Margin (NAAM) as reflected by redox sensitive-elements distributions in sediments

Science.gov (United States)

Gobeil, C.; Kuzyk, Z. Z. A.; Goni, M. A.; Macdonald, R. W.

2016-02-01

Concentrations of elements (S, Mn, Mo, U, Cd, Re) providing insights on organic C metabolized through oxidative processes at the sea floor were measured in 27 sediment cores collected along a section extending from the North Bering Sea to Davis Strait via the Canadian Archipelago. Sedimentary distributions and accumulation rates of these elements were used to i) document the relative importance of aerobic versus anaerobic degradation of organic C in NAAM sediments, ii) infer variations in water column carbon flux and iii) estimate the importance of this margin as a sink for key elements in the Arctic and global ocean. Distributions of Mn, total S and reduced inorganic S demonstrated that most sediments along the NAAM had relatively thick (>1 cm) surface oxic layers, underlain by sediments with weakly reducing conditions and limited sulphate reduction. Strongly reducing conditions accompanied by substantial sedimentary pyrite burial occurred only in certain subregions, including the Bering-Chukchi Shelves, shallow portions of Barrow Canyon. Estimated accumulation rates of authigenic S, Mo, Cd and U, and total Re displayed marked spatial variability that was related to sedimentary redox conditions induced by the supply of labile C to the seabed, as shown by significant relationships between the accumulation rates and vertical C flux, estimated from regional primary production values and water depth at the coring sites. High primary production combined with shallow water columns drive elevated rates of authigenic trace element accumulation in sediments from the Bering-Chukchi Shelves whereas low production combined with moderately deep conditions drive low rates of accumulation in sediments in the Beaufort Shelf, Davis Strait and Canadian Archipelago. Using the average authigenic trace element accumulation rates in sediments from the various regions, we submit that the shelves along the NAAM margin are important sinks in global marine biogeochemical budgets.

Distribution of flux-pinning energies in YBa2Cu3O(7-delta) and Bi2Sr2CaCu2O(8+delta) from flux noise

Science.gov (United States)

Ferrari, M. J.; Johnson, Mark; Wellstood, Frederick C.; Clarke, John; Mitzi, D.

1990-01-01

The spectral density of the magnetic flux noise measured in high-temperature superconductors in low magnetic fields scales approximately as the inverse of the frequency and increases with temperature. The temperature and frequency dependence of the noise are used to determine the pinning energies of individual flux vortices in thermal equilibrium. The distribution of pinning energies below 0.1 eV in YBa(2)Cu(3)O(7-delta) and near 0.2 eV in Bi(2)Sr(2)CaCu(2)O(8+delta). The noise power is proportional to the ambient magnetic field, indicating that the vortex motion is uncorrelated.

Effect of Magnetic Flux Density and Applied Current on Temperature, Velocity and Entropy Generation Distributions in MHD Pumps

Directory of Open Access Journals (Sweden)

M. Kiyasatfar

2011-01-01

Full Text Available In the present study, simulation of steady state, incompressible and fully developed laminar flow has been conducted in a magneto hydrodynamic (MHD pump. The governing equations are solved numerically by finite-difference method. The effect of the magnetic flux density and current on the flow and temperature distributions in a MHD pump is investigated. The obtained results showed that controlling the flow and the temperature is possible through the controlling of the applied current and the magnetic flux. Furthermore, the effects of the magnetic flux density and current on entropy generation in MHD pump are considered. Our presented numerical results are in good agreement with the experimental data showed in literature.

Metabolic engineering of deinococcus radiodurans based on computational analysis and functional genomics

Energy Technology Data Exchange (ETDEWEB)

Edwards, Jeremy, S.

2005-02-02

The objective of our work is to develop novel computational tools to analyze the Deinococcus radiodurans DNA repair pathways and the influence of the metabolic flux distribution on DNA repair. These tools will be applied to provide insights for metabolic engineering of strains capable of growing under nutrient poor conditions similar to those found in mixed contaminant sites of interest to the DOE. Over the entire grant period we accomplished all our specific aims and were also able to pursue new directions of research. Below, I will list the major accomplishments over the previous 3 years. (1) Performed Monte Carlo Simulations of RecA Mediated Pairing of Homologous DNA Molecules. (2) Developed a statistical approach to study the gene expression data from D. radiodurans. We have been studying the data from John Batista's. (3) Developed an expression profiling technology to generate very accurate and precise expression data. We followed up on results from John Batista's group using this approach. (4) Developed and put online a database for metabolic reconstructions. (5) We have developed and applied new Monte Carlo algorithms that are optimized for studying biological systems. (6) We developed a flux balance model for the D. radiodurans metabolic network

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

Apparatus for the measurement of the distribution of neutron flux (band and wire continuous recorders); Appareillage pour la mesure des repartitions de flux neutroniques (derouleurs a bandes et a fils)

Energy Technology Data Exchange (ETDEWEB)

Derrien, H; Lemerle, Y [Commissariat a l' Energie Atomique, Saclay (France). Centre d' Etudes Nucleaires

1963-07-01

The apparatus of which we describe the principles and the operation, makes it possible to know the thermal neutron flux distribution in a pile channel or along a fuel element by the measurement of the {beta} activity of continuous detectors. It is also possible thereby to show the presence of a very localised sudden discontinuity in the distribution curve. (authors) [French] Les appareils dont nous decrivons le principe et le fonctionnement, permettent de connaitre la repartition du flux de neutrons thermiques dans un canal de pile ou le long d'un element combustible, par la mesure de l'activite {beta} de detecteurs continus. Ils permettent en outre de mettre en evidence un accident brutal, tres localise, de la courbe de repartition. (auteurs)

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...

Sodium signaling and astrocyte energy metabolism

KAUST Repository

Chatton, Jean-Yves; Magistretti, Pierre J.; Barros, L. Felipe

2016-01-01

The Na+ gradient across the plasma membrane is constantly exploited by astrocytes as a secondary energy source to regulate the intracellular and extracellular milieu, and discard waste products. One of the most prominent roles of astrocytes in the brain is the Na+-dependent clearance of glutamate released by neurons during synaptic transmission. The intracellular Na+ load collectively generated by these processes converges at the Na,K-ATPase pump, responsible for Na+ extrusion from the cell, which is achieved at the expense of cellular ATP. These processes represent pivotal mechanisms enabling astrocytes to increase the local availability of metabolic substrates in response to neuronal activity. This review presents basic principles linking the intracellular handling of Na+ following activity-related transmembrane fluxes in astrocytes and the energy metabolic pathways involved. We propose a role of Na+ as an energy currency and as a mediator of metabolic signals in the context of neuron-glia interactions. We further discuss the possible impact of the astrocytic syncytium for the distribution and coordination of the metabolic response, and the compartmentation of these processes in cellular microdomains and subcellular organelles. Finally, we illustrate future avenues of investigation into signaling mechanisms aimed at bridging the gap between Na+ and the metabolic machinery. © 2016 Wiley Periodicals, Inc.

Sodium signaling and astrocyte energy metabolism

KAUST Repository

Chatton, Jean-Yves

2016-03-31

The Na+ gradient across the plasma membrane is constantly exploited by astrocytes as a secondary energy source to regulate the intracellular and extracellular milieu, and discard waste products. One of the most prominent roles of astrocytes in the brain is the Na+-dependent clearance of glutamate released by neurons during synaptic transmission. The intracellular Na+ load collectively generated by these processes converges at the Na,K-ATPase pump, responsible for Na+ extrusion from the cell, which is achieved at the expense of cellular ATP. These processes represent pivotal mechanisms enabling astrocytes to increase the local availability of metabolic substrates in response to neuronal activity. This review presents basic principles linking the intracellular handling of Na+ following activity-related transmembrane fluxes in astrocytes and the energy metabolic pathways involved. We propose a role of Na+ as an energy currency and as a mediator of metabolic signals in the context of neuron-glia interactions. We further discuss the possible impact of the astrocytic syncytium for the distribution and coordination of the metabolic response, and the compartmentation of these processes in cellular microdomains and subcellular organelles. Finally, we illustrate future avenues of investigation into signaling mechanisms aimed at bridging the gap between Na+ and the metabolic machinery. © 2016 Wiley Periodicals, Inc.

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....

Quantitative elementary mode analysis of metabolic pathways: the example of yeast glycolysis

Directory of Open Access Journals (Sweden)

Kanehisa Minoru

2006-04-01

Full Text Available Abstract Background Elementary mode analysis of metabolic pathways has proven to be a valuable tool for assessing the properties and functions of biochemical systems. However, little comprehension of how individual elementary modes are used in real cellular states has been achieved so far. A quantitative measure of fluxes carried by individual elementary modes is of great help to identify dominant metabolic processes, and to understand how these processes are redistributed in biological cells in response to changes in environmental conditions, enzyme kinetics, or chemical concentrations. Results Selecting a valid decomposition of a flux distribution onto a set of elementary modes is not straightforward, since there is usually an infinite number of possible such decompositions. We first show that two recently introduced decompositions are very closely related and assign the same fluxes to reversible elementary modes. Then, we show how such decompositions can be used in combination with kinetic modelling to assess the effects of changes in enzyme kinetics on the usage of individual metabolic routes, and to analyse the range of attainable states in a metabolic system. This approach is illustrated by the example of yeast glycolysis. Our results indicate that only a small subset of the space of stoichiometrically feasible steady states is actually reached by the glycolysis system, even when large variation intervals are allowed for all kinetic parameters of the model. Among eight possible elementary modes, the standard glycolytic route remains dominant in all cases, and only one other elementary mode is able to gain significant flux values in steady state. Conclusion These results indicate that a combination of structural and kinetic modelling significantly constrains the range of possible behaviours of a metabolic system. All elementary modes are not equal contributors to physiological cellular states, and this approach may open a direction toward a

Flux balance analysis predicts Warburg-like effects of mouse hepatocyte deficient in miR-122a.

Directory of Open Access Journals (Sweden)

Hua-Qing Wu

2017-07-01

Full Text Available The liver is a vital organ involving in various major metabolic functions in human body. MicroRNA-122 (miR-122 plays an important role in the regulation of liver metabolism, but its intrinsic physiological functions require further clarification. This study integrated the genome-scale metabolic model of hepatocytes and mouse experimental data with germline deletion of Mir122a (Mir122a-/- to infer Warburg-like effects. Elevated expression of MiR-122a target genes in Mir122a-/-mice, especially those encoding for metabolic enzymes, was applied to analyze the flux distributions of the genome-scale metabolic model in normal and deficient states. By definition of the similarity ratio, we compared the flux fold change of the genome-scale metabolic model computational results and metabolomic profiling data measured through a liquid-chromatography with mass spectrometer, respectively, for hepatocytes of 2-month-old mice in normal and deficient states. The Ddc gene demonstrated the highest similarity ratio of 95% to the biological hypothesis of the Warburg effect, and similarity of 75% to the experimental observation. We also used 2, 6, and 11 months of mir-122 knockout mice liver cell to examined the expression pattern of DDC in the knockout mice livers to show upregulated profiles of DDC from the data. Furthermore, through a bioinformatics (LINCS program prediction, BTK inhibitors and withaferin A could downregulate DDC expression, suggesting that such drugs could potentially alter the early events of metabolomics of liver cancer cells.

Software applications for flux balance analysis.

Science.gov (United States)

Lakshmanan, Meiyappan; Koh, Geoffrey; Chung, Bevan K S; Lee, Dong-Yup

2014-01-01

Flux balance analysis (FBA) is a widely used computational method for characterizing and engineering intrinsic cellular metabolism. The increasing number of its successful applications and growing popularity are possibly attributable to the availability of specific software tools for FBA. Each tool has its unique features and limitations with respect to operational environment, user-interface and supported analysis algorithms. Presented herein is an in-depth evaluation of currently available FBA applications, focusing mainly on usability, functionality, graphical representation and inter-operability. Overall, most of the applications are able to perform basic features of model creation and FBA simulation. COBRA toolbox, OptFlux and FASIMU are versatile to support advanced in silico algorithms to identify environmental and genetic targets for strain design. SurreyFBA, WEbcoli, Acorn, FAME, GEMSiRV and MetaFluxNet are the distinct tools which provide the user friendly interfaces in model handling. In terms of software architecture, FBA-SimVis and OptFlux have the flexible environments as they enable the plug-in/add-on feature to aid prospective functional extensions. Notably, an increasing trend towards the implementation of more tailored e-services such as central model repository and assistance to collaborative efforts was observed among the web-based applications with the help of advanced web-technologies. Furthermore, most recent applications such as the Model SEED, FAME, MetaFlux and MicrobesFlux have even included several routines to facilitate the reconstruction of genome-scale metabolic models. Finally, a brief discussion on the future directions of FBA applications was made for the benefit of potential tool developers.

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

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.

β-distribution for Reynolds stress and turbulent heat flux in relaxation turbulent boundary layer of compression ramp

Science.gov (United States)

Hu, YanChao; Bi, WeiTao; Li, ShiYao; She, ZhenSu

2017-12-01

A challenge in the study of turbulent boundary layers (TBLs) is to understand the non-equilibrium relaxation process after sep-aration and reattachment due to shock-wave/boundary-layer interaction. The classical boundary layer theory cannot deal with the strong adverse pressure gradient, and hence, the computational modeling of this process remains inaccurate. Here, we report the direct numerical simulation results of the relaxation TBL behind a compression ramp, which reveal the presence of intense large-scale eddies, with significantly enhanced Reynolds stress and turbulent heat flux. A crucial finding is that the wall-normal profiles of the excess Reynolds stress and turbulent heat flux obey a β-distribution, which is a product of two power laws with respect to the wall-normal distances from the wall and from the boundary layer edge. In addition, the streamwise decays of the excess Reynolds stress and turbulent heat flux also exhibit power laws with respect to the streamwise distance from the corner of the compression ramp. These results suggest that the relaxation TBL obeys the dilation symmetry, which is a specific form of self-organization in this complex non-equilibrium flow. The β-distribution yields important hints for the development of a turbulence model.

Feasibility study of Self Powered Neutron Detectors in Fast Reactors for detecting local change in neutron flux distribution

International Nuclear Information System (INIS)

Jammes, Christian; Filliatre, Philippe; Verma, Vasudha; Hellesen, Carl; Jacobsson Svard, Staffan

2015-01-01

Neutron flux monitoring system forms an integral part of the design of a Generation IV sodium cooled fast reactor system. Diverse possibilities of detector systems installation have to be investigated with respect to practicality and feasibility according to the detection parameters. In this paper, we demonstrate the feasibility of using self powered neutron detectors as in-core detectors in fast reactors for detecting local change in neutron flux distribution. We show that the gamma contribution from fission products decay in the fuel and activation of structural materials is very small compared to the fission gammas. Thus, it is possible for the in-core SPND signal to follow changes in local neutron flux as they are proportional to each other. This implies that the signal from an in-core SPND can provide dynamic information on the neutron flux perturbations occurring inside the reactor core. (authors)

Feasibility study of Self Powered Neutron Detectors in Fast Reactors for detecting local change in neutron flux distribution

Energy Technology Data Exchange (ETDEWEB)

Jammes, Christian; Filliatre, Philippe [CEA, DEN, DER, Instrumentation Sensors and Dosimetry Laboratory, Cadarache, F-13108 St Paul-Lez-Durance, (France); Verma, Vasudha; Hellesen, Carl; Jacobsson Svard, Staffan [Division of Applied Nuclear Physics, Uppsala University, SE-75120 Uppsala, (Sweden)

2015-07-01

Neutron flux monitoring system forms an integral part of the design of a Generation IV sodium cooled fast reactor system. Diverse possibilities of detector systems installation have to be investigated with respect to practicality and feasibility according to the detection parameters. In this paper, we demonstrate the feasibility of using self powered neutron detectors as in-core detectors in fast reactors for detecting local change in neutron flux distribution. We show that the gamma contribution from fission products decay in the fuel and activation of structural materials is very small compared to the fission gammas. Thus, it is possible for the in-core SPND signal to follow changes in local neutron flux as they are proportional to each other. This implies that the signal from an in-core SPND can provide dynamic information on the neutron flux perturbations occurring inside the reactor core. (authors)

High resolution isotope data and ensemble modelling reveal ecohydrological controls on catchment storage-discharge relationships and flux travel time distributions

Science.gov (United States)

Soulsby, C.; Kuppel, S.; Smith, A.; Tetzlaff, D.

2017-12-01

The dynamics of water storage in a catchment provides a fundamental insight into the interlinkages between input and output fluxes, and how these are affected by environmental change. Such dynamics also mediate, and help us understand, the fundamental difference of the rapid celerity of the rainfall-runoff (minutes to hours) response of catchments and the much slower velocity of water particles (months to decades) as they are transported through catchment systems. In this contribution we report an intensive, long-term (>10year), multi-scale isotope study in the Scottish Highlands that has sought to better understand these issues. We have integrated empirical data collection with diverse modelling approaches to quantify the dynamics and residence times of storage in different compartments of the hydrological system (vegetation canopies, soils, ground waters etc.) and their relationship between the magnitude and travel time distributions of output fluxes (stream flow, transpiration and evaporation). Use of conceptual, physically-based and probabilistic modelling approaches give broadly consistent perspectives on the storage-discharge relationships and the preferential selection of younger waters in runoff, evaporation and transpiration; while older waters predominate in groundwater. The work also highlighted the importance role vegetation plays in regulating fluxes in evaporation and transpiration and how this contributes to the differential ageing of water in mobile and bulk waters in the soil compartment. A separate case study shows how land use change can affect storage distributions in a catchment and radically change travel time distributions in output fluxes.

Calculations of Neutron Flux Distributions by Means of Integral Transport Methods

Energy Technology Data Exchange (ETDEWEB)

Carlvik, I

1967-05-15

Flux distributions have been calculated mainly in one energy group, for a number of systems representing geometries interesting for reactor calculations. Integral transport methods of two kinds were utilised, collision probabilities (CP) and the discrete method (DIT). The geometries considered comprise the three one-dimensional geometries, planes, sphericals and annular, and further a square cell with a circular fuel rod and a rod cluster cell with a circular outer boundary. For the annular cells both methods (CP and DIT) were used and the results were compared. The purpose of the work is twofold, firstly to demonstrate the versatility and efficacy of integral transport methods and secondly to serve as a guide for anybody who wants to use the methods.

Thermodynamics-based Metabolite Sensitivity Analysis in metabolic networks.

Science.gov (United States)

Kiparissides, A; Hatzimanikatis, V

2017-01-01

The increasing availability of large metabolomics datasets enhances the need for computational methodologies that can organize the data in a way that can lead to the inference of meaningful relationships. Knowledge of the metabolic state of a cell and how it responds to various stimuli and extracellular conditions can offer significant insight in the regulatory functions and how to manipulate them. Constraint based methods, such as Flux Balance Analysis (FBA) and Thermodynamics-based flux analysis (TFA), are commonly used to estimate the flow of metabolites through genome-wide metabolic networks, making it possible to identify the ranges of flux values that are consistent with the studied physiological and thermodynamic conditions. However, unless key intracellular fluxes and metabolite concentrations are known, constraint-based models lead to underdetermined problem formulations. This lack of information propagates as uncertainty in the estimation of fluxes and basic reaction properties such as the determination of reaction directionalities. Therefore, knowledge of which metabolites, if measured, would contribute the most to reducing this uncertainty can significantly improve our ability to define the internal state of the cell. In the present work we combine constraint based modeling, Design of Experiments (DoE) and Global Sensitivity Analysis (GSA) into the Thermodynamics-based Metabolite Sensitivity Analysis (TMSA) method. TMSA ranks metabolites comprising a metabolic network based on their ability to constrain the gamut of possible solutions to a limited, thermodynamically consistent set of internal states. TMSA is modular and can be applied to a single reaction, a metabolic pathway or an entire metabolic network. This is, to our knowledge, the first attempt to use metabolic modeling in order to provide a significance ranking of metabolites to guide experimental measurements. Copyright © 2016 International Metabolic Engineering Society. Published by Elsevier

Application of dynamic flux balance analysis to an industrial Escherichia coli fermentation.

Science.gov (United States)

Meadows, Adam L; Karnik, Rahi; Lam, Harry; Forestell, Sean; Snedecor, Brad

2010-03-01

We have developed a reactor-scale model of Escherichia coli metabolism and growth in a 1000 L process for the production of a recombinant therapeutic protein. The model consists of two distinct parts: (1) a dynamic, process specific portion that describes the time evolution of 37 process variables of relevance and (2) a flux balance based, 123-reaction metabolic model of E. coli metabolism. This model combines several previously reported modeling approaches including a growth rate-dependent biomass composition, maximum growth rate objective function, and dynamic flux balancing. In addition, we introduce concentration-dependent boundary conditions of transport fluxes, dynamic maintenance demands, and a state-dependent cellular objective. This formulation was able to describe specific runs with high-fidelity over process conditions including rich media, simultaneous acetate and glucose consumption, glucose minimal media, and phosphate depleted media. Furthermore, the model accurately describes the effect of process perturbations--such as glucose overbatching and insufficient aeration--on growth, metabolism, and titer. (c) 2009 Elsevier Inc. All rights reserved.

Distribution of flux-pinning energies in YBa2Cu3O7-δ and Bi2Sr2CaCu2O8+δ from flux noise

International Nuclear Information System (INIS)

Ferrari, M.J.; Johnson, M.; Wellstood, F.C.; Clarke, J.; Mitzi, D.; Rosenthal, P.A.; Eom, C.B.; Geballe, T.H.; Kapitulnik, A.; Beasley, M.R.

1990-01-01

The spectral density of the magnetic flux noise measured in high-temperature superconductors in low magnetic fields scales approximately as the inverse of the frequency and increases with temperature. We use the temperature and frequency dependence of the noise to determine the pinning energies of individual flux vortices in thermal equilibrium. The distribution of pinning energies peaks below 0.1 eV in YBa 2 Cu 3 O 7-δ and near 0.2 eV in Bi 2 Sr 2 CaCu 2 O 8+δ . The noise power is proportional to the ambient magnetic field, indicating that the vortex motion is uncorrelated

An analog computer method for solving flux distribution problems in multi region nuclear reactors

Energy Technology Data Exchange (ETDEWEB)

Radanovic, L; Bingulac, S; Lazarevic, B; Matausek, M [Boris Kidric Institute of Nuclear Sciences Vinca, Beograd (Yugoslavia)

1963-04-15

The paper describes a method developed for determining criticality conditions and plotting flux distribution curves in multi region nuclear reactors on a standard analog computer. The method, which is based on the one-dimensional two group treatment, avoids iterative procedures normally used for boundary value problems and is practically insensitive to errors in initial conditions. The amount of analog equipment required is reduced to a minimum and is independent of the number of core regions and reflectors. (author)

Construction and simulation of the Bradyrhizobium diazoefficiens USDA110 metabolic network: a comparison between free-living and symbiotic states.

Science.gov (United States)

Yang, Yi; Hu, Xiao-Pan; Ma, Bin-Guang

2017-02-28

Bradyrhizobium diazoefficiens is a rhizobium able to convert atmospheric nitrogen into ammonium by establishing mutualistic symbiosis with soybean. It has been recognized as an important parent strain for microbial agents and is widely applied in agricultural and environmental fields. In order to study the metabolic properties of symbiotic nitrogen fixation and the differences between a free-living cell and a symbiotic bacteroid, a genome-scale metabolic network of B. diazoefficiens USDA110 was constructed and analyzed. The metabolic network, iYY1101, contains 1031 reactions, 661 metabolites, and 1101 genes in total. Metabolic models reflecting free-living and symbiotic states were determined by defining the corresponding objective functions and substrate input sets, and were further constrained by high-throughput transcriptomic and proteomic data. Constraint-based flux analysis was used to compare the metabolic capacities and the effects on the metabolic targets of genes and reactions between the two physiological states. The results showed that a free-living rhizobium possesses a steady state flux distribution for sustaining a complex supply of biomass precursors while a symbiotic bacteroid maintains a relatively condensed one adapted to nitrogen-fixation. Our metabolic models may serve as a promising platform for better understanding the symbiotic nitrogen fixation of this species.

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)

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...

Transient critical heat flux under flow coast-down in vertical annulus with non-uniform heat flux distribution

International Nuclear Information System (INIS)

Moon, S.K.; Chun, S.Y.; Choi, K.Y.; Yang, S.K.

2001-01-01

An experimental study on transient critical heat flux (CHF) under flow coast-down has been performed for water flow in a non-uniformly heated vertical annulus under low flow and a wide range of pressure conditions. The objectives of this study are to systematically investigate the effect of the flow transient on the CHF and to compare the transient CHF with steady state CHF. The transient CHF experiments have been performed for three kinds of flow transient modes based on the coast-down data of the Kori 3/4 nuclear power plant reactor coolant pump. Most of the CHFs occurred in the annular-mist flow regime. Thus, it means that the possible CHF mechanism might be the liquid film dryout in the annular-mist flow regime. For flow transient mode with the smallest flow reduction rate, the time-to-CHF is the largest. At the same inlet subcooling, system pressure and heat flux, the effect of the initial mass flux on the critical mass flux can be negligible. However, the effect of the initial mass flux on the time-to-CHF becomes large as the heat flux decreases. Usually, the critical mass flux is large for slow flow reduction. There is a pressure effect on the ratio of the transient CHF data to steady state CHF data. Some conventional correlations show relatively better CHF prediction results for high system pressure, high quality and slow transient modes than for low system pressure, low quality and fast transient modes. (author)

QUANTITATIVE ANALYSIS OF FLUX REGULATION THROUGH HIERARCHICAL REGULATION ANALYSIS

NARCIS (Netherlands)

van Eunen, Karen; Rossell, Sergio; Bouwman, Jildau; Westerhoff, Hans V.; Bakker, Barbara M.; Jameson, D; Verma, M; Westerhoff, HV

2011-01-01

Regulation analysis is a methodology that quantifies to what extent a change in the flux through a metabolic pathway is regulated by either gene expression or metabolism. Two extensions to regulation analysis were developed over the past years: (i) the regulation of V(max) can be dissected into the

Quantitative analysis of flux regulation through hierarchical regulation analysis

NARCIS (Netherlands)

Eunen, K. van; Rossell, S.; Bouwman, J.; Westerhoff, H.V.; Bakker, B.M.

2011-01-01

Regulation analysis is a methodology that quantifies to what extent a change in the flux through a metabolic pathway is regulated by either gene expression or metabolism. Two extensions to regulation analysis were developed over the past years: (i) the regulation of Vmax can be dissected into the

Forearm metabolism during infusion of adrenaline

DEFF Research Database (Denmark)

Simonsen, L; Stefl, B; Bülow, J

2000-01-01

Human skeletal muscle metabolism is often investigated by measurements of substrate fluxes across the forearm. To evaluate whether the two forearms give the same metabolic information, nine healthy subjects were studied in the fasted state and during infusion of adrenaline. Both arms were...... catheterized in a cubital vein in the retrograde direction. A femoral artery was catheterized for blood sampling, and a femoral vein for infusion of adrenaline. Forearm blood flow was measured by venous occlusion strain-gauge plethysmography. Forearm subcutaneous adipose tissue blood flow was measured...... by the local 133Xe washout method. Metabolic fluxes were calculated as the product of forearm blood flow and a-v differences of metabolite concentrations. After baseline measurements, adrenaline was infused at a rate of 0.3 nmol kg-1 min-1. No difference in the metabolic information obtained in the fasting...

Simulating Serial-Target Antibacterial Drug Synergies Using Flux Balance Analysis

DEFF Research Database (Denmark)

Krueger, Andrew S.; Munck, Christian; Dantas, Gautam

2016-01-01

Flux balance analysis (FBA) is an increasingly useful approach for modeling the behavior of metabolic systems. However, standard FBA modeling of genetic knockouts cannot predict drug combination synergies observed between serial metabolic targets, even though such synergies give rise to some of t...

Theoretical analysis of nuclear reactors (Phase I), I-V, Part V, Determining the fine flux distribution

International Nuclear Information System (INIS)

Pop-Jordanov, J.

1962-07-01

Mono energetic neutron transport equation was solved by Carlson numerical method in cylindrical geometry. S n code was developed for the digital computer ZUSE Z23. Neutron flux distribution was determined for the RA reactor cell by applying S 4 approximation. Reactor cell was treated as D 2 O-U-D 2 O system. Time of iteration was 185 s [sr

Flux and energy deposition distribution studies inside the irradiation room of the portuguese 60Co irradiation facility

International Nuclear Information System (INIS)

Portugal, Luis; Oliveira, Carlos

2008-01-01

Full text: In December 2003 the irradiator of the Portuguese 60 Co irradiation facility, UTR, was replenished. Eighteen new sources were loaded and the older ones (156) were rearranged. The result was an irradiator with about 10.2 P Bq of total activity. The active area of the irradiator has also increased. Now it uses twenty five of the thirty tubes of the source rack, nine more than in the previous geometry. This facility was designed mainly for sterilisation of medical devices. However it is also used for the irradiation of other products such as cork stoppers, plastics and a limited number of food and feed. The purpose of this work is to perform dosimetric studies inside the irradiation room of a 60 Co irradiation facility, particularly, the flux and energy deposition distributions. The MCNPX code was used for the simulation of the facility. The track average mesh tally capabilities of MCNPX were used to plot the photon flux and energy deposition distributions. This tool provides a fast way for flux and energy deposition mapping. The absorbed dose distribution near the walls of the irradiation room was also calculated. Instead of using meshtallys as before, the average absorbed dose inside boxes lined with the walls was determined and afterwards a plot of its distribution was made. The absorbed dose rates obtained ranged from 5 to 500 Gy.h -1 depending on material being irradiated in process and the location on the wall. These positions can be useful for fixed irradiation purposes. Both dosimetric studies were done considering two different materials being irradiated in the process: cork stoppers and water, materials with quite different densities (0.102 and 1 g.cm-3, respectively). These studies showed some important characteristics of the radiation fields inside the irradiation room, namely its spatial heterogeneity. Tunnelling and shadow effects were enhanced when the product boxes increases its density. Besides a deeper dosimetric understanding of the

Distribution of hydrogen-metabolizing bacteria in alfalfa field soil

International Nuclear Information System (INIS)

Cunningham, S.D.; Kapulnik, Y.; Phillips, D.A.

1986-01-01

H 2 evolved by alfalfa root nodules during the process of N 2 fixation may be an important factor influencing the distribution of soil bacteria. To test this hypothesis under field conditions, over 700 bacterial isolates were obtained from fallow soil or from the 3-mm layer of soil surrounding alfalfa (Medicago sativa L.) root nodules, alfalfa roots, or bindweed (Convolvulus arvensis L.) roots. Bacteria were isolated under either aerobic or microaerophilic conditions and were tested for their capacity to metabolize H 2 . Isolates showing net H 2 uptake and 3 H 2 incorporation activity under laboratory conditions were assigned a Hup + phenotype, whereas organisms with significant H 2 output capacity were designated as a Hout + phenotype. Under aerobic isolation conditions two Hup + isolates were obtained, whereas under microaerophilic conditions five Hup + and two Hout + isolates were found. The nine isolates differed on the basis of 24 standard bacteriological characteristics or fatty acid composition. Five of the nine organisms were isolated from soil around root nodules, whereas the other four were found distributed among the other three soil environments. On the basis of the microaerophilic isolations, 4.8% of the total procaryotic isolates from soil around root nodules were capable of oxidizing H 2 , and 1.2% could produce H 2 . Two of the Hup + isolates were identified as Rhizobium meliloti by root nodulation tests, but the fact that none of the isolates reduced C 2 H 2 under the assay conditions suggested that the H 2 metabolism traits were associated with various hydrogenase systems rather than with nitrogenase activity

Random distribution of nucleoli in metabolic cells

Energy Technology Data Exchange (ETDEWEB)

Beckman, R.J.; Waterman, M.S.

1977-01-01

Hasofer (1974) has studied a probabilistic model for the fusion of nucleoli in metabolic cells. The nucleoli are uniformly distributed at points in the nucleus, assumed to be a sphere. The nucleoli grow from a point to a maximum size during interphase, and fusion is said to occur if the nucleoli touch. For this model, Hasofer calculated the probability of fusion and found it much smaller than experimental data would indicate. Experimental data of this type is taken by use of a microscope where a two-dimensional view or projection of the three-dimensional cell is obtained. Hasofer implicitly assumes that actual fusion can be distinguished from the case where the two nucleoli do not touch but their two-dimensional projections overlap. It is assumed, in this letter, that these two cases cannot be distinguished. The probability obtained by Beckman and Waterman is larger than Hasofer's and a much better fit to the experimental data is obtained. Even if true fusion can be unfailingly distinguished from overlap of the two-dimensional projections, it is hoped that these calculations will allow someone to propose the correct (non-uniform) model. It is concluded, for the assumptions used, that there is not sufficient evidence to reject the hypothesis of uniform distribution of the nucleoli.

Validation of absolute axial neutron flux distribution calculations with MCNP with 197Au(n,γ)198Au reaction rate distribution measurements at the JSI TRIGA Mark II reactor.

Science.gov (United States)

Radulović, Vladimir; Štancar, Žiga; Snoj, Luka; Trkov, Andrej

2014-02-01

The calculation of axial neutron flux distributions with the MCNP code at the JSI TRIGA Mark II reactor has been validated with experimental measurements of the (197)Au(n,γ)(198)Au reaction rate. The calculated absolute reaction rate values, scaled according to the reactor power and corrected for the flux redistribution effect, are in good agreement with the experimental results. The effect of different cross-section libraries on the calculations has been investigated and shown to be minor. Copyright © 2013 Elsevier Ltd. All rights reserved.

Heat tranfer decrease during water boiling in a tube for the heat flux step distribution by the tube length

International Nuclear Information System (INIS)

Remizov, O.V.; Sergeev, V.V.; Yurkov, Yu.I.

1983-01-01

The effect of the heat flux distribution along the circular tube length on supercritical convective heat transfer at parameters typical for steam generators heated by liquid metal is studied. The effect of conditions in a under- and a supercritical zones of a vertical tube with independently heated lower and upper sections on supercritical convective heat transfer is studied on a water circulation loop at 9.8-17.7 MPa pressure and 330-1000 kg/m 2 s mass velocities. The experimental heat fluxes varied within the following limits: at the upper section from 0 to 474 kW/m 2 , at the lower section from 190 to 590 kW/m 2 . Analysis of the obtained data shows that when heat flux changes in the supercritical zone rewetting of the heated surface and simultaneous existence of two critical zones are observed. The effect of heat flux in the supercritical zone on convective heat transfer is ambiguous: the heat flux growth up to 60-100 kW/m 2 leads to increasing minimum values of the heat transfer factor in the supercritical zone, and a further heat flux growth - to their reduction. The conclusion is made that the value of heat flux in the undercritical zone affects convective heat transfer in the supercritical zone mainly through changing the value of critical vapour content

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.

A technical basis for the flux corrected local conditions critical heat flux correlation

International Nuclear Information System (INIS)

Luxat, J.C.

2008-01-01

The so-called 'flux-corrected' local conditions CHF correlation was developed at Ontario Hydro in the 1980's and was demonstrated to successfully correlate the Onset of Intermittent Dryout (OID) CHF data for 37-element fuel with a downstream-skewed axial heat flux distribution. However, because the heat flux correction factor appeared to be an ad-hoc, albeit a successful modifying factor in the correlation, there was reluctance to accept the correlation more generally. This paper presents a thermalhydraulic basis, derived from two-phase flow considerations, that supports the appropriateness of the heat flux correction as a local effects modifying factor. (author)

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...

Estimation of subcriticality and fuel concentration by using 'pattern matching' of neutron flux distribution under non uniformed system

International Nuclear Information System (INIS)

Ishitani, Kazuki; Yamane, Yoshihiro

1999-01-01

In nuclear fuel reprocessing plants, monitoring the spatial profile of neutron flux to infer subcriticality and distribution of fuel concentration using detectors such as PSPC, is very beneficial in sight of criticality safety. In this paper a method of subcriticality and fuel concentration estimation which is supposed to use under non-uniformed system is proposed. Its basic concept is the pattern matching between measured neutron flux distribution and beforehand calculated one. In any kind of subcriticality estimation, we can regard that measured neutron counts put any kind of black box, and then this black box outputs subcriticality. We proposed the use of artificial neural network or 'pattern matching' as black box which have no theoretical clear base. These method are wholly based on the calculated value as recently advancement of computer code accuracy for criticality safety. The most difference between indirect bias estimation method and our method is that our new approach target are the unknown non-uniform system. (J.P.N.)

Effect of the geometrical parameters of an optical integrator on the unformity of the radiation flux distribution

International Nuclear Information System (INIS)

Vishnyakova, T.P.; Klychev, Sh.I.

1992-01-01

The use of optical mixers in the optical irradiators of simulators of direct and concentrated solar radiation has been proposed. In this paper, the parameters of an optical mixer are calculated geometrically, and the effect of the parameters of the optical mixer on the unformity of the irradiance distribution η of the radiation flux on the detector is investigated. These investigations show that the light distribution from an optical mixer is close to the characteristics of an ideal uniform emitter within the region from 0 to the limit of α. 5 refs., 4 figs

Spatial distribution of the neutron flux in the IEA-R1 reactor core obtained by means of foil activation

International Nuclear Information System (INIS)

Mestnik Filho, J.

1979-01-01

A three-dimensional distribution of the neutron flux in IEA-R1 reactor, obtained by activating gold foils, is presented. The foils of diameter 8mm and thickness 0,013mm were mounted on lucite plates and located between the fuel element plates. Foil activities were measured using a 3x3 inches Nal(Tl) scintilation detector calibrated against a 4πβγ coincidence detector. Foil positions were chosen to minimize the errors of measurement; the overall estimated error on the measured flux is 5%. (Author) [pt

Assessment of 12 CHF prediction methods, for an axially non-uniform heat flux distribution, with the RELAP5 computer code

Energy Technology Data Exchange (ETDEWEB)

Ferrouk, M. [Laboratoire du Genie Physique des Hydrocarbures, University of Boumerdes, Boumerdes 35000 (Algeria)], E-mail: m_ferrouk@yahoo.fr; Aissani, S. [Laboratoire du Genie Physique des Hydrocarbures, University of Boumerdes, Boumerdes 35000 (Algeria); D' Auria, F.; DelNevo, A.; Salah, A. Bousbia [Dipartimento di Ingegneria Meccanica, Nucleare e della Produzione, Universita di Pisa (Italy)

2008-10-15

The present article covers the evaluation of the performance of twelve critical heat flux methods/correlations published in the open literature. The study concerns the simulation of an axially non-uniform heat flux distribution with the RELAP5 computer code in a single boiling water reactor channel benchmark problem. The nodalization scheme employed for the considered particular geometry, as modelled in RELAP5 code, is described. For this purpose a review of critical heat flux models/correlations applicable to non-uniform axial heat profile is provided. Simulation results using the RELAP5 code and those obtained from our computer program, based on three type predictions methods such as local conditions, F-factor and boiling length average approaches were compared.

Metabolic response of Geobacter sulfurreducens towards electron donor/acceptor variation

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Lovley Derek R

2010-11-01

Full Text Available Abstract Background Geobacter sulfurreducens is capable of coupling the complete oxidation of organic compounds to iron reduction. The metabolic response of G. sulfurreducens towards variations in electron donors (acetate, hydrogen and acceptors (Fe(III, fumarate was investigated via 13C-based metabolic flux analysis. We examined the 13C-labeling patterns of proteinogenic amino acids obtained from G. sulfurreducens cultured with 13C-acetate. Results Using 13C-based metabolic flux analysis, we observed that donor and acceptor variations gave rise to differences in gluconeogenetic initiation, tricarboxylic acid cycle activity, and amino acid biosynthesis pathways. Culturing G. sulfurreducens cells with Fe(III as the electron acceptor and acetate as the electron donor resulted in pyruvate as the primary carbon source for gluconeogenesis. When fumarate was provided as the electron acceptor and acetate as the electron donor, the flux analysis suggested that fumarate served as both an electron acceptor and, in conjunction with acetate, a carbon source. Growth on fumarate and acetate resulted in the initiation of gluconeogenesis by phosphoenolpyruvate carboxykinase and a slightly elevated flux through the oxidative tricarboxylic acid cycle as compared to growth with Fe(III as the electron acceptor. In addition, the direction of net flux between acetyl-CoA and pyruvate was reversed during growth on fumarate relative to Fe(III, while growth in the presence of Fe(III and acetate which provided hydrogen as an electron donor, resulted in decreased flux through the tricarboxylic acid cycle. Conclusions We gained detailed insight into the metabolism of G. sulfurreducens cells under various electron donor/acceptor conditions using 13C-based metabolic flux analysis. Our results can be used for the development of G. sulfurreducens as a chassis for a variety of applications including bioremediation and renewable biofuel production.

Hepatocyte heterogeneity in the metabolism of carbohydrates.

Science.gov (United States)

Jungermann, K; Thurman, R G

1992-01-01

Periportal and perivenous hepatocytes possess different amounts and activities of the rate-generating enzymes of carbohydrate and oxidative energy metabolism and thus different metabolic capacities. This is the basis of the model of metabolic zonation, according to which periportal cells catalyze predominantly the oxidative catabolism of fatty and amino acids as well as glucose release and glycogen formation via gluconeogenesis, and perivenous cells carry out preferentially glucose uptake for glycogen synthesis and glycolysis coupled to liponeogenesis. The input of humoral and nervous signals into the periportal and perivenous zones is different; gradients of oxygen, substrates and products, hormones and mediators and nerve densities exist which are important not only for the short-term regulation of carbohydrate metabolism but also for the long-term regulation of zonal gene expression. The specialization of periportal and perivenous hepatocytes in carbohydrate metabolism has been well characterized. In vivo evidence is provided by the complex metabolic situation termed the 'glucose paradox' and by zonal flux differences calculated on the basis of the distribution of enzymes and metabolites. In vitro evidence is given by the different flux rates determined with classical invasive techniques, e.g. in periportal-like and perivenous-like hepatocytes in cell culture, in periportal- and perivenous-enriched hepatocyte populations and in perfused livers during orthograde and retrograde flow, as well as with noninvasive techniques using miniature oxygen electrodes, e.g. in livers perfused in either direction. Differences of opinion in the interpretation of studies with invasive and noninvasive techniques by the authors are discussed. The declining gradient in oxygen concentrations, the decreasing glucagon/insulin ratio and the different innervation could be important factors in the zonal expression of the genes of carbohydrate-metabolizing enzymes. While it is clear that

Comparison between measured and computed magnetic flux density distribution of simulated transformer core joints assembled from grain-oriented and non-oriented electrical steel

Directory of Open Access Journals (Sweden)

Hamid Shahrouzi

2018-04-01

Full Text Available The flux distribution in an overlapped linear joint constructed in the central region of an Epstein Square was studied experimentally and results compared with those obtained using a computational magnetic field solver. High permeability grain-oriented (GO and low permeability non-oriented (NO electrical steels were compared at a nominal core flux density of 1.60 T at 50 Hz. It was found that the experimental results only agreed well at flux densities at which the reluctance of different paths of the flux are similar. Also it was revealed that the flux becomes more uniform when the working point of the electrical steel is close to the knee point of the B-H curve of the steel.

SVD identifies transcript length distribution functions from DNA microarray data and reveals evolutionary forces globally affecting GBM metabolism.

Directory of Open Access Journals (Sweden)

Nicolas M Bertagnolli

Full Text Available To search for evolutionary forces that might act upon transcript length, we use the singular value decomposition (SVD to identify the length distribution functions of sets and subsets of human and yeast transcripts from profiles of mRNA abundance levels across gel electrophoresis migration distances that were previously measured by DNA microarrays. We show that the SVD identifies the transcript length distribution functions as "asymmetric generalized coherent states" from the DNA microarray data and with no a-priori assumptions. Comparing subsets of human and yeast transcripts of the same gene ontology annotations, we find that in both disparate eukaryotes, transcripts involved in protein synthesis or mitochondrial metabolism are significantly shorter than typical, and in particular, significantly shorter than those involved in glucose metabolism. Comparing the subsets of human transcripts that are overexpressed in glioblastoma multiforme (GBM or normal brain tissue samples from The Cancer Genome Atlas, we find that GBM maintains normal brain overexpression of significantly short transcripts, enriched in transcripts that are involved in protein synthesis or mitochondrial metabolism, but suppresses normal overexpression of significantly longer transcripts, enriched in transcripts that are involved in glucose metabolism and brain activity. These global relations among transcript length, cellular metabolism and tumor development suggest a previously unrecognized physical mode for tumor and normal cells to differentially regulate metabolism in a transcript length-dependent manner. The identified distribution functions support a previous hypothesis from mathematical modeling of evolutionary forces that act upon transcript length in the manner of the restoring force of the harmonic oscillator.

Pathway Thermodynamics Highlights Kinetic Obstacles in Central Metabolism

Science.gov (United States)

Flamholz, Avi; Reznik, Ed; Liebermeister, Wolfram; Milo, Ron

2014-01-01

In metabolism research, thermodynamics is usually used to determine the directionality of a reaction or the feasibility of a pathway. However, the relationship between thermodynamic potentials and fluxes is not limited to questions of directionality: thermodynamics also affects the kinetics of reactions through the flux-force relationship, which states that the logarithm of the ratio between the forward and reverse fluxes is directly proportional to the change in Gibbs energy due to a reaction (ΔrG′). Accordingly, if an enzyme catalyzes a reaction with a ΔrG′ of -5.7 kJ/mol then the forward flux will be roughly ten times the reverse flux. As ΔrG′ approaches equilibrium (ΔrG′ = 0 kJ/mol), exponentially more enzyme counterproductively catalyzes the reverse reaction, reducing the net rate at which the reaction proceeds. Thus, the enzyme level required to achieve a given flux increases dramatically near equilibrium. Here, we develop a framework for quantifying the degree to which pathways suffer these thermodynamic limitations on flux. For each pathway, we calculate a single thermodynamically-derived metric (the Max-min Driving Force, MDF), which enables objective ranking of pathways by the degree to which their flux is constrained by low thermodynamic driving force. Our framework accounts for the effect of pH, ionic strength and metabolite concentration ranges and allows us to quantify how alterations to the pathway structure affect the pathway's thermodynamics. Applying this methodology to pathways of central metabolism sheds light on some of their features, including metabolic bypasses (e.g., fermentation pathways bypassing substrate-level phosphorylation), substrate channeling (e.g., of oxaloacetate from malate dehydrogenase to citrate synthase), and use of alternative cofactors (e.g., quinone as an electron acceptor instead of NAD). The methods presented here place another arrow in metabolic engineers' quiver, providing a simple means of evaluating

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.

Neutron flux distribution measurement in the Fort St. Vrain initial core (results of Fort St. Vrain start-up test A-7)

International Nuclear Information System (INIS)

Marshall, A.C.; Brown, J.R.

1975-01-01

A description is given of a test to measure the axial flux distribution at several radial locations in the Fort St. Vrain core representing unrodded, rodded, and partially rodded regions. The measurements were intended to verify the calculational accuracy of the three-dimensional calculational model used to compute axial power distributions for the Fort St. Vrain core. (U.S.)

Slave nodes and the controllability of metabolic networks

International Nuclear Information System (INIS)

Kim, Dong-Hee; Motter, Adilson E

2009-01-01

Recent work on synthetic rescues has shown that the targeted deletion of specific metabolic genes can often be used to rescue otherwise non-viable mutants. This raises a fundamental biophysical question: to what extent can the whole-cell behavior of a large metabolic network be controlled by constraining the flux of one or more reactions in the network? This touches upon the issue of the number of degrees of freedom contained by one such network. Using the metabolic network of Escherichia coli as a model system, here we address this question theoretically by exploring not only reaction deletions, but also a continuum of all possible reaction expression levels. We show that the behavior of the metabolic network can be largely manipulated by the pinned expression of a single reaction. In particular, a relevant fraction of the metabolic reactions exhibits canalizing interactions, in that the specification of one reaction flux determines cellular growth as well as the fluxes of most other reactions in optimal steady states. The activity of individual reactions can thus be used as surrogates to monitor and possibly control cellular growth and other whole-cell behaviors. In addition to its implications for the study of control processes, our methodology provides a new approach to study how the integrated dynamics of the entire metabolic network emerges from the coordinated behavior of its component parts.

Electron energy distribution control by fiat: breaking from the conventional flux ratio scaling rules in etch

Science.gov (United States)

Ranjan, Alok; Wang, Mingmei; Sherpa, Sonam; Ventzek, Peter

2015-03-01

With shrinking critical dimensions, minimizing each of aspect ratio dependent etching (ARDE), bowing, undercut, selectivity, and within die uniformly across a wafer is met by trading off one requirement against another. The problem of trade-offs is especially critical. At the root of the problem is that roles radical flux, ion flux and ion energy play may be both good and bad. Increasing one parameter helps meeting one requirement but hinders meeting the other. Managing process by managing flux ratios and ion energy alone with conventional sources is not adequate because surface chemistry is uncontrollable. At the root of lack of control is that the electron energy distribution function (eedf) has not been controlled. Fortunately the high density surface wave sources control the eedf by fiat. High density surface wave sources are characterized by distinct plasma regions: an active plasma generation region with high electron temperature (Te) and an ionization free but chemistry rich diffusive region (low Te region). Pressure aids is segregating the regions by proving a means for momentum relaxation between the source and downstream region. "Spatial pulsing" allows access to plasma chemistry with reasonably high ion flux, from the active plasma generation region, just above the wafer. Low plasma potential enables precise passivation of surfaces which is critical for atomic layer etch (ALE) or high precision etch where the roles of plasma species can be limited to their purposed roles. High precision etch need not be at the cost of speed and manufacturability. Large ion flux at precisely controlled ion energy with RLSATM realizes fast desorption steps for ALE without compromising process throughput and precision.

Engineering of metabolic control

Science.gov (United States)

Liao, James C.

2004-03-16

The invention features a method of producing heterologous molecules in cells under the regulatory control of a metabolite and metabolic flux. The method can enhance the synthesis of heterologous polypeptides and metabolites.

A simulation model of distributions of radiational flux at leaf surfaces in crowns of fruit trees

International Nuclear Information System (INIS)

Yamamoto, T.

1988-01-01

A computer-model was constructed for estimating distributions with time of radiational fluxes at leaf surfaces throughout fruit tree canopies in which leaves did not distribute uniformely in three dimensional space. Several assumptions were set up to construct the model for approximation of using solid geometry. For irregular distribution of leaf area in three dimensional space data were used in the simulation as number of leaves per internal cubic bloc of a cubic grid (n-divided per side). Several main parameters used were peculiar to fruit species which contain parameters (λ, ν) of Beta function to calculate both probability density function of leaf area distribution with respect to inclination angle and leaf extinction coefficient for parallel beam by leaves parameters (A, R i ) to calculate stem extinction coefficient for parallel beam, and parameters (D i ) to calculate leaf extinction coefficient of downward transmission and downward reflection. With these data and parameters solid geometry and Lambert-Beer's law constituted this model

Signaling Pathways Regulating Redox Balance in Cancer Metabolism.

Science.gov (United States)

De Santis, Maria Chiara; Porporato, Paolo Ettore; Martini, Miriam; Morandi, Andrea

2018-01-01

The interplay between rewiring tumor metabolism and oncogenic driver mutations is only beginning to be appreciated. Metabolic deregulation has been described for decades as a bystander effect of genomic aberrations. However, for the biology of malignant cells, metabolic reprogramming is essential to tackle a harsh environment, including nutrient deprivation, reactive oxygen species production, and oxygen withdrawal. Besides the well-investigated glycolytic metabolism, it is emerging that several other metabolic fluxes are relevant for tumorigenesis in supporting redox balance, most notably pentose phosphate pathway, folate, and mitochondrial metabolism. The relationship between metabolic rewiring and mutant genes is still unclear and, therefore, we will discuss how metabolic needs and oncogene mutations influence each other to satisfy cancer cells' demands. Mutations in oncogenes, i.e., PI3K/AKT/mTOR, RAS pathway, and MYC, and tumor suppressors, i.e., p53 and liver kinase B1, result in metabolic flexibility and may influence response to therapy. Since metabolic rewiring is shaped by oncogenic driver mutations, understanding how specific alterations in signaling pathways affect different metabolic fluxes will be instrumental for the development of novel targeted therapies. In the era of personalized medicine, the combination of driver mutations, metabolite levels, and tissue of origins will pave the way to innovative therapeutic interventions.

Theoretical analysis of nuclear reactors (Phase II), I-V, Part V, Determining the fine neutron flux distribution by Pn method

International Nuclear Information System (INIS)

Pop-Jordanov, J.

1962-10-01

Expression for spherical harmonic moments were applied. They were obtained by spherical harmonics expansion of monoenergetic transport equation. This report presents the procedure for calculating the neutron flux distribution in the nine-zone reactor cell of the RA reactor in Vinca. The procedure was modelled for digital computer ZUSE Z-23 by expansion of the diagram of the automated P 3 code, which is adequate for P n code with minor changes. The needed subroutines were developed. The most important ones were those for modified first and second order Bessel functions of n-th order. Computer Z-23 was operating only 15 hours during three months, and thus only the subroutines for modified Bessel functions could be tested and the obtained results were excellent. For the mentioned reason the neutron flux distribution will be calculated in the forthcoming period [sr

PAH distribution and mass fluxes in the Three Gorges Reservoir after impoundment of the Three Gorges Dam.

Science.gov (United States)

Deyerling, Dominik; Wang, Jingxian; Hu, Wei; Westrich, Bernhard; Peng, Chengrong; Bi, Yonghong; Henkelmann, Bernhard; Schramm, Karl-Werner

2014-09-01

Mass fluxes of polycyclic aromatic hydrocarbons (PAHs) were calculated for the Three Gorges Reservoir (TGR) in China, based on concentration and discharge data from the Yangtze River. Virtual Organisms (VOs) have been applied during four campaigns in 2008, 2009 (twice) and 2011 at sampling sites distributed from Chongqing to Maoping. The total PAH mass fluxes ranged from 110 to 2,160 mg s(-1). Highest loads were determined at Chongqing with a decreasing trend towards Maoping in all four sampling campaigns. PAH remediation capacity of the TGR was found to be high as the mass flux reduced by more than half from upstream to downstream. Responsible processes are thought to be adsorption of PAH to suspended particles, dilution and degradation. Furthermore, the dependence of PAH concentration upon water depth was investigated at Maoping in front of the Three Gorges Dam. Although considerable differences could be revealed, there was no trend observable. Sampling of water with self-packed filter cartridges confirmed more homogenous PAH depth distribution. Moreover, PAH content of suspended particles was estimated from water concentrations gathered by VOs based on a water-particle separation model and subsequently compared to PAH concentration measured in water and in filter cartridges. It could be shown that the modeled data predicts the concentration caused by particle-bound PAHs to be about 6 times lower than PAHs dissolved in water. Besides, the model estimates the proportions of 5- and 6-ring PAHs being higher than in water phase. Copyright © 2014 Elsevier B.V. All rights reserved.

maximum neutron flux at thermal nuclear reactors

International Nuclear Information System (INIS)

Strugar, P.

1968-10-01

Since actual research reactors are technically complicated and expensive facilities it is important to achieve savings by appropriate reactor lattice configurations. There is a number of papers, and practical examples of reactors with central reflector, dealing with spatial distribution of fuel elements which would result in higher neutron flux. Common disadvantage of all the solutions is that the choice of best solution is done starting from the anticipated spatial distributions of fuel elements. The weakness of these approaches is lack of defined optimization criteria. Direct approach is defined as follows: determine the spatial distribution of fuel concentration starting from the condition of maximum neutron flux by fulfilling the thermal constraints. Thus the problem of determining the maximum neutron flux is solving a variational problem which is beyond the possibilities of classical variational calculation. This variational problem has been successfully solved by applying the maximum principle of Pontrjagin. Optimum distribution of fuel concentration was obtained in explicit analytical form. Thus, spatial distribution of the neutron flux and critical dimensions of quite complex reactor system are calculated in a relatively simple way. In addition to the fact that the results are innovative this approach is interesting because of the optimization procedure itself [sr

Thermal neutron flux distribution in ET-RR-2 reactor thermal column

Directory of Open Access Journals (Sweden)

Imam Mahmoud M.

2002-01-01

Full Text Available The thermal column in the ET-RR-2 reactor is intended to promote a thermal neutron field of high intensity and purity to be used for following tasks: (a to provide a thermal neutron flux in the neutron transmutation silicon doping, (b to provide a thermal flux in the neutron activation analysis position, and (c to provide a thermal neutron flux of high intensity to the head of one of the beam tubes leading to the room specified for boron thermal neutron capture therapy. It was, therefore, necessary to determine the thermal neutron flux at above mentioned positions. In the present work, the neutron flux in the ET-RR-2 reactor system was calculated by applying the three dimensional diffusion depletion code TRITON. According to these calculations, the reactor system is composed of the core, surrounding external irradiation grid, beryllium block, thermal column and the water reflector in the reactor tank next to the tank wall. As a result of these calculations, the thermal neutron fluxes within the thermal column and at irradiation positions within the thermal column were obtained. Apart from this, the burn up results for the start up core calculated according to the TRITION code were compared with those given by the reactor designer.

A preliminary assessment of the effects of heat flux distribution and penetration on the creep rupture of a reactor vessel lower head

International Nuclear Information System (INIS)

Chu, T.Y.; Bentz, J.; Simpson, R.; Witt, R.

1997-01-01

The objective of the Lower Head Failure (LHF) Experiment Program is to experimentally investigate and characterize the failure of the reactor vessel lower head due to thermal and pressure loads under severe accident conditions. The experiment is performed using 1/5-scale models of a typical PWR pressure vessel. Experiments are performed for various internal pressure and imposed heat flux distributions with and without instrumentation guide tube penetrations. The experimental program is complemented by a modest modeling program based on the application of vessel creep rupture codes developed in the TMI Vessel Investigation Project. The first three experiments under the LHF program investigated the creep rupture of simulated reactor pressure vessels without penetrations. The heat flux distributions for the three experiments are uniform (LHF-1), center-peaked (LHF-2), and side-peaked (LHF-3), respectively. For all the experiments, appreciable vessel deformation was observed to initiate at vessel wall temperatures above 900K and the vessel typically failed at approximately 1000K. The size of failure was always observed to be smaller than the heated region. For experiments with non-uniform heat flux distributions, failure typically occurs in the region of peak temperature. A brief discussion of the effect of penetration is also presented

Redox balance is key to explaining full vs. partial switching to low-yield metabolism

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van Hoek Milan JA

2012-03-01

Full Text Available Abstract Background Low-yield metabolism is a puzzling phenomenon in many unicellular and multicellular organisms. In abundance of glucose, many cells use a highly wasteful fermentation pathway despite the availability of a high-yield pathway, producing many ATP molecules per glucose, e.g., oxidative phosphorylation. Some of these organisms, including the lactic acid bacterium Lactococcus lactis, downregulate their high-yield pathway in favor of the low-yield pathway. Other organisms, including Escherichia coli do not reduce the flux through the high-yield pathway, employing the low-yield pathway in parallel with a fully active high-yield pathway. For what reasons do some species use the high-yield and low-yield pathways concurrently and what makes others downregulate the high-yield pathway? A classic rationale for metabolic fermentation is overflow metabolism. Because the throughput of metabolic pathways is limited, influx of glucose exceeding the pathway's throughput capacity is thought to be redirected into an alternative, low-yield pathway. This overflow metabolism rationale suggests that cells would only use fermentation once the high-yield pathway runs at maximum rate, but it cannot explain why cells would decrease the flux through the high-yield pathway. Results Using flux balance analysis with molecular crowding (FBAwMC, a recent extension to flux balance analysis (FBA that assumes that the total flux through the metabolic network is limited, we investigate the differences between Saccharomyces cerevisiae and L. lactis that downregulate the high-yield pathway at increasing glucose concentrations, and E. coli, which keeps the high-yield pathway functioning at maximal rate. FBAwMC correctly predicts the metabolic switching mode in these three organisms, suggesting that metabolic network architecture is responsible for differences in metabolic switching mode. Based on our analysis, we expect gradual, "overflow-like" switching behavior in

Understanding Regulation of Metabolism through Feasibility Analysis

Science.gov (United States)

Nikerel, Emrah; Berkhout, Jan; Hu, Fengyuan; Teusink, Bas; Reinders, Marcel J. T.; de Ridder, Dick

2012-01-01

Understanding cellular regulation of metabolism is a major challenge in systems biology. Thus far, the main assumption was that enzyme levels are key regulators in metabolic networks. However, regulation analysis recently showed that metabolism is rarely controlled via enzyme levels only, but through non-obvious combinations of hierarchical (gene and enzyme levels) and metabolic regulation (mass action and allosteric interaction). Quantitative analyses relating changes in metabolic fluxes to changes in transcript or protein levels have revealed a remarkable lack of understanding of the regulation of these networks. We study metabolic regulation via feasibility analysis (FA). Inspired by the constraint-based approach of Flux Balance Analysis, FA incorporates a model describing kinetic interactions between molecules. We enlarge the portfolio of objectives for the cell by defining three main physiologically relevant objectives for the cell: function, robustness and temporal responsiveness. We postulate that the cell assumes one or a combination of these objectives and search for enzyme levels necessary to achieve this. We call the subspace of feasible enzyme levels the feasible enzyme space. Once this space is constructed, we can study how different objectives may (if possible) be combined, or evaluate the conditions at which the cells are faced with a trade-off among those. We apply FA to the experimental scenario of long-term carbon limited chemostat cultivation of yeast cells, studying how metabolism evolves optimally. Cells employ a mixed strategy composed of increasing enzyme levels for glucose uptake and hexokinase and decreasing levels of the remaining enzymes. This trade-off renders the cells specialized in this low-carbon flux state to compete for the available glucose and get rid of over-overcapacity. Overall, we show that FA is a powerful tool for systems biologists to study regulation of metabolism, interpret experimental data and evaluate hypotheses. PMID

Axial and radial distribution of neutron fluxes in the irradiation channels of the Ghana Research Reactor-1 using foil activation analysis and Monte Carlo

International Nuclear Information System (INIS)

Abrefah, G.R.

2009-02-01

The Monte-Carlo method and experimental methods were used to determine the neutron fluxes in the irradiation channels of the Ghana Research Reactor -1. The MCNP5 code was used for this purpose to simulate the radial and axial distribution of the neutron fluxes within all the ten irradiation channels. The results obtained were compared with the experimental results. After the MCNP simulation and experimental procedure, it was observed that axially, the fluxes rise to a peak before falling and then finally leveling out. Axially and radially, it was also observed that the fluxes in the centre of the channels were lower than on the sides. Radially, the fluxes dip in the centre while it increases steadily towards the sides of the channels. The results have shown that there are flux variations within the irradiation channels both axially and radially. (au)

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.

The flux distribution from a 1.25m2 target aligned heliostat: comparison of ray tracing and experimental results

CSIR Research Space (South Africa)

Maliage, M

2012-05-01

Full Text Available The purpose of this paper is to validate SolTrace for concentrating solar investigations at CSIR by means of a test case: the comparison of the flux distribution in the focal spot of a 1.25 m2 target aligned heliostat predicted by the ray tracing...

Development of an intracellular glycolytic flux sensor for high throughput applications in E.coli

DEFF Research Database (Denmark)

Lehning, Christina Eva

The aim of this PhD project was to construct, test and apply an intracellular, growth-­‐ independent and direct measureable glycolytic flux biosensor in E. coli. Studying the metabolic flux of bacterial cells is of growing interest as it is of fundamental importance to bacterial physiology as well...... to study the flux-­‐altering effects of gene knockouts in E. coli at the single cell level in a vastly parallelized and high-­‐throughput manner. After growth for several generations in rich and minimal media, 2126 gene knockouts, mainly outside of the core metabolism, could be screened. 3 gene knockouts...

Numerical simulation of a fractional model of temperature distribution and heat flux in the semi infinite solid

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Anupama Choudhary

2016-03-01

Full Text Available In this paper, a fractional model for the computation of temperature and heat flux distribution in a semi-infinite solid is discussed which is subjected to spatially decomposing, time-dependent laser source. The apt dimensionless parameters are identified and the reduced temperature and heat flux as a function of these parameters are presented in a numerical form. Some special cases of practical interest are also discussed. The solution is derived by the application of the Laplace transform, the Fourier sine transform and their derivatives. Also, we developed an alternative solution of it by using the Sumudu transform, the Fourier transform and their derivatives. These results are received in compact and graceful forms in terms of the generalized Mittag-Leffler function, which are suitable for numerical computation.

Distribution, regional sources and deposition fluxes of organochlorine pesticides in precipitation in Guangzhou, South China

Science.gov (United States)

Huang, De-Yin; Peng, Ping'an; Xu, Yi-Gang; Sun, Cui-Xiang; Deng, Hong-Mei; Deng, Yun-Yun

2010-07-01

We analyzed rainwater collected from multiple sites, Guangzhou, China, from March to August 2005, with the aim to characterize the distribution, regional sources and deposition fluxes of organochlorine pesticides (OCPs) in South China. Eight species of organochlorine pesticide were detected, including hexachlorocyclohexanes (HCHs), dichlorodiphenyltrichloroethanes (DDTs), and endosulfans. Volume-weighted mean monthly total concentrations varied from 3.65 ± 0.95 to 9.37 ± 2.63 ng L - 1 , and the estimated total wet deposition flux was about 11.43 ± 3.27 µg m - 2 during the monitoring period. Pesticides were mainly detected in the dissolved phase. Distribution coefficients between particulate and dissolved phases in March and April were generally higher than in other months. HCHs, p,p'-DDD and p,p'-DDT in precipitation were attributed to both the residues and present usage of insecticides in Pearl River Delta. The concentrations of p,p'-DDD + p,p'-DDT were relatively high from April to August, which were related to the usage of antifouling paints containing DDT for fishing ships in seaports of the South China Sea in summer. In contrast, endosulfans were relatively high in March, which was related to their seasonal atmospheric transport from cotton fields in eastern China by the Asian winter monsoon. The consistency of the variation of endosulfans, p,p'-DDD and p,p'-DDT concentrations with the alternation of summer and winter monsoon suggested that the Asian monsoon played an important role in the long-range transport of OCPs. In addition, the wet deposition of OCPs may influence not only Pearl River water but also the surface land distributions of pesticides in the Guangzhou area, especially for endosulfans, p,p'-DDD and p,p'-DDT.

Common variants near MC4R in relation to body fat, body fat distribution, metabolic traits and energy expenditure

DEFF Research Database (Denmark)

Kring, Sofia Inez Iqbal; Holst, C; Toubro, Søren

2010-01-01

Common variants near melanocortin receptor 4 (MC4R) have been related to fatness and type 2 diabetes. We examined the associations of rs17782313 and rs17700633 in relation to body fat, body fat distribution, metabolic traits, weight development and energy expenditure.......Common variants near melanocortin receptor 4 (MC4R) have been related to fatness and type 2 diabetes. We examined the associations of rs17782313 and rs17700633 in relation to body fat, body fat distribution, metabolic traits, weight development and energy expenditure....

Metabolic responses to pyruvate kinase deletion in lysine producing Corynebacterium glutamicum

Directory of Open Access Journals (Sweden)

Wittmann Christoph

2008-03-01

Full Text Available Abstract Background Pyruvate kinase is an important element in flux control of the intermediate metabolism. It catalyzes the irreversible conversion of phosphoenolpyruvate into pyruvate and is under allosteric control. In Corynebacterium glutamicum, this enzyme was regarded as promising target for improved production of lysine, one of the major amino acids in animal nutrition. In pyruvate kinase deficient strains the required equimolar ratio of the two lysine precursors oxaloacetate and pyruvate can be achieved through concerted action of the phosphotransferase system (PTS and phosphoenolpyruvate carboxylase (PEPC, whereby a reduced amount of carbon may be lost as CO2 due to reduced flux into the tricarboxylic acid (TCA cycle. In previous studies, deletion of pyruvate kinase in lysine-producing C. glutamicum, however, did not yield a clear picture and the exact metabolic consequences are not fully understood. Results In this work, deletion of the pyk gene, encoding pyruvate kinase, was carried out in the lysine-producing strain C. glutamicum lysCfbr, expressing a feedback resistant aspartokinase, to investigate the cellular response to deletion of this central glycolytic enzyme. Pyk deletion was achieved by allelic replacement, verified by PCR analysis and the lack of in vitro enzyme activity. The deletion mutant showed an overall growth behavior (specific growth rate, glucose uptake rate, biomass yield which was very similar to that of the parent strain, but differed in slightly reduced lysine formation, increased formation of the overflow metabolites dihydroxyacetone and glycerol and in metabolic fluxes around the pyruvate node. The latter involved a flux shift from pyruvate carboxylase (PC to PEPC, by which the cell maintained anaplerotic supply of the TCA cycle. This created a metabolic by-pass from PEP to pyruvate via malic enzyme demonstrating its contribution to metabolic flexibility of C. glutamicum on glucose. Conclusion The metabolic

Characterization of ion fluxes and heat fluxes for PMI relevant conditions on Proto-MPEX

Science.gov (United States)

Beers, Clyde; Shaw, Guinevere; Biewer, Theodore; Rapp, Juergen

2016-10-01

Plasma characterization, in particular, particle flux and electron and ion temperature distributions nearest to an exposed target, are critical to quantifying Plasma Surface Interaction (PSI). In the Proto-Material Plasma Exposure eXperiment (Proto-MPEX), the ion fluxes and heat fluxes are derived from double Langmuir Probes (DLP) and Thomson Scattering in front of the target assuming Bohm conditions at the sheath entrance. Power fluxes derived from ne and Te measurements are compared to heat fluxes measured with IR thermography. The comparison will allow conclusions on the sheath heat transmission coefficient to be made experimentally. Different experimental conditions (low and high density plasmas (0.5 - 6 x 1019 m-3) with different magnetic configuration are compared. This work was supported by the U.S. D.O.E. contract DE-AC05-00OR22725.

Characterizability of metabolic pathway systems from time series data.

Science.gov (United States)

Voit, Eberhard O

2013-12-01

Over the past decade, the biomathematical community has devoted substantial effort to the complicated challenge of estimating parameter values for biological systems models. An even more difficult issue is the characterization of functional forms for the processes that govern these systems. Most parameter estimation approaches tacitly assume that these forms are known or can be assumed with some validity. However, this assumption is not always true. The recently proposed method of Dynamic Flux Estimation (DFE) addresses this problem in a genuinely novel fashion for metabolic pathway systems. Specifically, DFE allows the characterization of fluxes within such systems through an analysis of metabolic time series data. Its main drawback is the fact that DFE can only directly be applied if the pathway system contains as many metabolites as unknown fluxes. This situation is unfortunately rare. To overcome this roadblock, earlier work in this field had proposed strategies for augmenting the set of unknown fluxes with independent kinetic information, which however is not always available. Employing Moore-Penrose pseudo-inverse methods of linear algebra, the present article discusses an approach for characterizing fluxes from metabolic time series data that is applicable even if the pathway system is underdetermined and contains more fluxes than metabolites. Intriguingly, this approach is independent of a specific modeling framework and unaffected by noise in the experimental time series data. The results reveal whether any fluxes may be characterized and, if so, which subset is characterizable. They also help with the identification of fluxes that, if they could be determined independently, would allow the application of DFE. Copyright © 2013 Elsevier Inc. All rights reserved.

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).

Understanding the anisotropic ion distributions within magnetotail dipolarizing flux bundles